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2026-04-01 00:00:00
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41163695
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Clinical and Demographic Correlates of Pornography Addiction: A Cross-sectional Study from India.
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Pornography addiction is a growing public health concern worldwide, with increasing recognition of its prevalence and consequences in India. This study explores the onset, manifestation, and impact of pornography addiction within the Indian context, addressing the need for culturally relevant research. A retrospective, observational, cross-sectional study was conducted using data from 589 individuals who sought treatment for pornography addiction through online and offline healthcare platforms. Patients aged 18 and older were included based on the International Classification of Diseases, 11th Revision (ICD-11) diagnostic criteria for Compulsive Sexual Behavior Disorder (CSBD) (6C72). Data on demographic factors, clinical diagnoses, and treatment outcomes were analyzed using International Business Machines Statistical Package for the Social Sciences (IBM SPSS). Participants received either pharmacological treatment, psychotherapy, or a combination of both. The sample included 589 participants, predominantly male (<i>n</i> = 583; 98.98%), with a mean age of 28.98 years; 374 (63.5%) were under 30, and 287 (48.7%) were single. Most identified as heterosexual (<i>n</i> = 568; 96.4%) and had no prior treatment history (<i>n</i> = 465; 78.9%). Common co-morbid sexual dysfunctions included erectile dysfunction (<i>n</i> = 232; 39.4%), premature ejaculation (<i>n</i> = 198; 33.6%), and low sexual desire (<i>n</i> = 109; 18.5%). Pharmacological treatment was most common (<i>n</i> = 338; 57.4%), followed by psychotherapy (<i>n</i> = 207; 35.2%) and combined treatment (<i>n</i> = 44; 7.4%). Age showed significant associations with addiction severity (<i>χ</i>² = 17.07, <i>p</i> = .01), relationship status (<i>χ</i>² = 190.11, <i>p</i> < .01), and treatment modality (<i>χ</i>² = 12.25, <i>p</i> = .01), with younger individuals more often receiving psychotherapy. Severity was weakly but significantly correlated with both age (<i>r</i> = 0.149, <i>p</i> < .01) and number of psychiatric diagnoses (<i>r</i> = 0.098, <i>p</i> < .05). Pornography addiction in India is shaped by age, relationship status, and cultural context. These findings underscore the need for age-targeted, culturally informed interventions. Future research should examine longitudinal trends and psychiatric comorbidities to guide comprehensive treatment planning.
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2025-10-26
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41165541
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Wellness Curriculum to Promote Resilience.
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Burnout as a public health crisis has gained attention in recent years. Integrating a wellness curriculum into training programs can reduce burnout and cultivate the awareness and skills needed to support a sustainable career in health care. The faculty midwives within the residency program in obstetrics and gynecology at The Warren Alpert Medical School of Brown University have implemented a successful, evidence-based wellness curriculum for residents that focuses on the emotional, physical, and psychological needs of learners. Participants report that this program increases work satisfaction and reduces burnout. The initiative could be modified across many disciplines of clinical training, and with midwife learners, to decrease stress during an academically rigorous and emotionally overwhelming time and provide trainees with tools that will sustain their sense of well-being throughout their careers.
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2025-10-30
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41197969
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Burden Beyond the Bedside: A Global Synthesis of Depression in Informal Cancer Caregivers: An Umbrella Review.
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The aim of this umbrella review is to synthesize pooled prevalence of existing evidence on depressive morbidity among informal cancer caregivers. This umbrella review was conducted in accordance with PRISMA guidelines, and the protocol was registered in PROSPERO (CRD420251032522). A comprehensive search of major databases was performed to identify relevant studies. Predefined inclusion and exclusion criteria were applied. The corrected covered area (CCA) was calculated to assess overlap, and the methodological quality of included reviews was evaluated using the AMSTAR 2 tool. This umbrella review included four systematic reviews and meta-analyses, comprising a total of 160 primary studies with 40,605 participants worldwide. The pooled global prevalence of depression among informal caregivers of cancer patients was 38% (95% CI: 28%-48%). However, prevalence estimates varied widely, ranging from 4% to 55%, likely due to differences in the depression assessment tools used across studies. In conclusion, this review reveals a high prevalence of depression among informal caregivers of cancer patients a burden comparable to or exceeding that observed in other chronic illnesses and global crises such as the COVID-19 pandemic. Integrating routine mental health screening using validated tools such as the CES-D or PHQ-9 into oncology care is essential. Structured interventions including counseling, psych-education, and respite care should be embedded within care pathways. Future research should prioritize standardized assessment tools and caregiver-focused strategies to enhance comparability and guide best practices. Policymakers must invest in caregiver mental health to ensure sustainable and compassionate cancer care systems.
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2025-11-04
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41198258
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Pulmonary Disease in the Older Adult: A Review of Interstitial Lung Disease.
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Interstitial lung diseases (ILDs) are a group of diverse conditions of critical importance to the care of the older adult that can cause pulmonary fibrosis, respiratory failure, and death. Aging and geriatric principles are key factors in the epidemiology, pathogenesis, and management of ILD. Effective management of ILD for the older adult includes prompt diagnosis and referral for treatment, including pharmacotherapy, pulmonary rehabilitation, and symptom palliation. It is key to recognize and address age-related geriatric syndromes in order to deliver age-friendly ILD care. Important gaps remain in how best to tailor and deliver care for older adults with ILD.
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2025-11-01
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41197662
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Impact of liver cirrhosis on postoperative outcomes following total hip and knee arthroplasty : a systematic review and meta-analysis.
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Cirrhosis is a known comorbidity that may influence outcomes following total joint replacement (TJR). This meta-analysis evaluates the impact of cirrhosis on postoperative complications and mortality after TJR. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Four databases were searched up to February 2025. Studies comparing the outcomes of TJR in cirrhotic versus non-cirrhotic patients were included. Data were analyzed using a random-effects model, and subgroup and sensitivity analyses were performed. A total of 12 studies, including 12.8 million TJR cases, were analyzed, with 111,011 cirrhotic patients. Cirrhosis was significantly associated with higher rates of mortality (odds ratio (OR) = 4.67, 95% CI 2.58 to 8.43), revision surgery (OR = 2.13, 95% CI 1.60 to 2.83), periprosthetic joint infection (OR = 2.61, 95% CI 2.11 to 3.21), implant failure (OR = 1.86, 95% CI 1.58 to 2.18), prosthetic fracture (OR = 1.89, 95% CI 1.19 to 3.01), transfusion (OR = 1.73, 95% CI 1.56 to 1.92), pneumonia (OR = 1.35, 95% CI 1.17 to 1.56), acute renal failure (OR = 2.16, 95% CI 1.35 to 3.46), readmission (OR = 1.93, 95% CI 1.70 to 2.20), and extended hospital stay (SMD = 0.49, 95% CI 0.28 to 0.69). Gastrointestinal complications (OR = 0.72) and pulmonary thromboembolism (OR = 0.25) were significantly lower. No significant differences were observed for wound complications, bleeding volume, operating time, venous thromboembolism, or cardiac events. Cirrhotic patients undergoing TJR are at greater risk for mortality, complications, and healthcare resource use. These findings underscore the need for multidisciplinary preoperative evaluation and careful risk-benefit assessment to improve outcomes in this vulnerable population.
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2025-11-07
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41190951
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CCD2MD: A Suite of Packages for Preparing Co-Folded Outputs for Molecular Dynamics Simulations.
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Protein-lipid interactions play a crucial role in the stability and function of membrane proteins. While experimental approaches to characterize these interactions in a native-like membrane environment can be challenging, computational techniques offer a powerful alternative for identifying and analyzing potential binding sites. Recent advances in cofolding methods now enable the prediction of holo protein structures, capturing conformational changes that may occur upon lipid binding and thereby improving the accuracy of binding site characterization. However, the outputs from these methods often require postprocessing to ensure compatibility with widely used molecular dynamics force fields. In this work, we introduce CCD2MD, a modular toolkit designed to convert cofolding outputs into simulation-ready systems for GROMACS. CCD2MD supports both atomistic and coarse-grained representations with or without membrane embedding. While CCD2MD is exemplified here with protein-lipid systems, its modular design allows for straightforward adaptation to other cofolded biomolecular assemblies, incorporating complexes with nucleic acids, small molecules, carbohydrates, or metal ions, thereby enabling a variety of simulation setups across multiple scales.
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2025-11-05
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41175797
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Computed tomography (CT) structured reporting generation based on the intelligent assisted diagnosis system for rectal cancer staging and evaluation of its clinical application.
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To evaluate the clinical utility of the intelligent assisted diagnosis system for rectal cancer staging (IADS-R) in aiding radiologists of varying levels of experience to produce computed tomography (CT) structured reporting (SR). Six hundred fifty abdominal enhanced CT datasets from rectal cancer patients were collected, with tumour and lymph node regions annotated. Four hundred images were used to train IADS-R's convolutional neural network model and 250 images were used for validation. By comparing the consistency and accuracy of diagnostic staging, the consistency of SR measurements, and the time efficiency in report generation among three groups of physicians (senior radiologists, junior radiologists, and junior radiologists assisted by IADS-R), the study demonstrated the supportive role of IADS-R for junior radiologists. Junior radiologists with IADS-R assistance achieved diagnostic accuracy rates of 81.2% for T-staging and 81.6% for N-staging, comparable to senior radiologists (78.0% for T and 77.6% for N) and significantly higher than unassisted juniors (60.8% for T and 55.2% for N). SR generated by junior radiologists with IADS-R assistance were more consistent with senior radiologists' reports, particularly in measuring tumour size and proximity to pelvic tissue structures. Report generation time for IADS-R-assisted juniors (1773.1s) matched seniors and was faster than unassisted juniors (2356.1s). With the assistance of IADS-R, the efficiency and accuracy of junior radiologists in producing SR have been significantly improved. IADS-R significantly improved junior radiologists' accuracy and efficiency in rectal cancer staging and SR generation, reaching levels comparable to senior radiologists.
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2025-10-06
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41165208
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An optimized, high-throughput workflow for the collection, processing, and visualization of histology data in comparative vertebrate morphogenesis.
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In an era where the diversity and quality of imaging modalities is rapidly increasing, it may seem counterintuitive to promote classical histology as a critical skill. It is a mistake, however, to assume that the heuristic potential of these high-resolution histological data is stagnant. Deep learning algorithms have emerged as an efficient tool for converting and quantifying the cellular resolution of 2D histology sections as detailed 3D models, capable of being integrated with a diversity of multi-omics data. Such analytical innovation requires large numbers of high-quality slides whose construction faces a variety of technical challenges. These challenges are exaggerated for developmental and evolutionary biologists, for whom ontogeny and phylogeny are critical variables that require additional sampling. Our goal is to provide a protocol optimized for the thin-section histology of vertebrate embryos, detailing best practices for sample collection, processing, and slide preparation. We hope that by: (1) synthesizing a scattered methodological literature that often excludes embryological tissues, and (2) recommending adjustments to common techniques like dehydration, xylene infiltration, and sectioning, other researchers may bypass the frustrating and time-consuming problems we encountered and move quickly to producing the high-quality histological data that modern developmental biology is likely to demand.
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2025-10-30
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41187392
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Antineoplastic and antibacterial activity of new copper(II) complexes with H₂salbu and H₄salbu Schiff base-type ligands.
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This study explores the structural, electronic, and biological properties of ten copper(II) complexes with Schiff bases (N,N'-bis(5,5'-R-salicylidene)-1,4-butanediamine)) ([Cu<sub>2</sub>(MeO-L1)<sub>2</sub>], [Cu<sub>2</sub>(Me-L2)<sub>2</sub>], [Cu(H-L3)], [Cu(Cl-L4)] and [Cu(NO<sub>2</sub>-L5)]), and their hydrogenated ligands (N,N'-Bis(5,5'-R-salicyl)butylenediamine) ([Cu(MeO-LH1)], [Cu(Me-LH2)], [Cu(H-LH3)], [Cu(Cl-LH4)] and [Cu(NO<sub>2</sub>-LH5)]). The complexes were characterized by, elemental analysis, IR, Uv-vis, mass spectrometry, EPR, and cyclic voltammetry. The crystal structure of [Cu<sub>2</sub>(MeO-L1)<sub>2</sub>], [Cu<sub>2</sub>(Me-L2)<sub>2</sub>], and [Cu(H-L3)] were determined via single crystal X-ray diffraction, revealing orthorhombic and monoclinic systems with space groups P2<sub>1</sub>, C222<sub>1</sub>, and Pbca, respectively. X-ray diffraction, also, confirmed distorted square-planar geometries for the complexes. EPR spectra, recorded in DMSO solution at 77 K, indicated axial anisotropy and confirmed distorted square-planar geometries for most complexes and suggested a covalent character in metal-ligand bonding. Cyclic voltammetry revealed reversible redox behavior for Schiff base complexes and irreversible processes for hydrogenated ligands, with electron-withdrawing substituents favoring reduction processes. The results demonstrate the significant influence of ligand flexibility and substituent effects on the electronic properties and coordination geometry of the complexes, with electron-withdrawing groups favoring reduction processes. Biological assays demonstrated that [Cu<sub>2</sub>(Me-L2)<sub>2</sub>] and [Cu(Cl-LH4)] exhibited significant antiproliferative activity against A549 and HeLa cancer cell lines, surpassing cisplatin in efficacy. The leishmanicidal activity of [Cu(Cl-LH4)] and ligands H-L3, H-LH3 and Cl-LH4 showed potent inhibitory effects on Leishmania mexicana, with no cytotoxicity on RAW 264.7 macrophages. These findings underscore the potential of these copper(II) complexes for therapeutic applications, influenced by ligand flexibility and substituent effects.
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2025-10-24
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41201708
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Evaluation of coronary artery calcium score by age and sex: a multicenter study.
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To evaluate coronary artery calcium (CAC) scores in a large Turkish cohort using age- and sex-specific percentiles, and to assess the agreement between CAD-RADS plaque burden scores and percentile-based CAC classification. A total of 4,887 clinically referred patients who underwent coronary CT angiography (CCTA) with non-contrast imaging were retrospectively evaluated. CAC scores were calculated using the Agatston method. Percentile reference values were generated according to age, sex, and number of cardiovascular risk factors. "Coronary age" was estimated by matching each individual's CAC score to the 50th percentile value. The agreement between CAD-RADS P scores and percentile-based classification was assessed using Cohen's kappa. Age, male sex, and traditional risk factors (hypertension, diabetes, hyperlipidemia, and smoking) were significantly associated with higher CAC scores (p < 0.01). The likelihood of CAC > 0 increased with each additional risk factor. Among individuals with low to intermediate cardiovascular risk, 22.3% had CAC scores above the 75th percentile. ROC analysis showed strong discriminatory ability for risk factor-based prediction of CAC > 0 (AUC = 0.873). However, agreement between CAD-RADS P scores and percentile-based classification was poor (κ = 0.12, p < 0.01). Absolute CAC scores do not reliably reflect relative risk in younger or low-risk individuals. Percentile-based interpretation and coronary age estimation offer a more individualized approach, particularly valuable in low-to-intermediate risk populations.
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2025-11-07
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41173334
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Streamlined construction of episomal vectors for rapid assessment of fusion phytase display in Saccharomyces cerevisiae.
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We developed a fusion phytase combining acid- and alkaline-active phytases, displayed on Saccharomyces cerevisiae cells. Recombinant replicative vectors were constructed to harbor phytase expression cassettes, enabling rapid screening of fusion enzyme constructs. This system provides a preliminary approach for optimizing phytase display prior to genomic integration.
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2025-10-29
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41173039
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Centralization for reducing medial meniscal extrusion after root tear repair appears effective but is technique-dependent : a systematic review.
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The aim of this systematic review was to examine whether meniscal centralization techniques, including posteromedial suture anchor (PMA) and posteromedial transtibial pullout repair (PMP), when added to conventional medial meniscus root repair, could affect the outcomes. A systematic search was conducted in four electronic databases (PubMed, Embase, Scopus, and Web of Science) to identify studies that adopted meniscal reinforcement techniques to reduce the extruded meniscus in patients with pathological root tear and medial meniscal extrusion (MME). The required data, comprising study characteristics, centralization techniques, and outcome measures, were extracted from eligible studies. A total of 11 studies, including 474 total patients, were identified. Two major techniques were used: PMA (five studies) and PMP (five studies). One study used a combination of both. In terms of clinical scores, MME, and osteoarthritis progression, review of five comparative studies found that all three reported no benefit to using the PMP technique, while both showed significant advantages using the PMA technique. A review of the studies in the PMA group reported significant improvements in MME (range of MME mean difference (MD) -1.2 mm to -0.2 mm). Conflicting results were seen in the PMP group, in which some even showed increased extrusion (range of MME MD -0.50 mm to +1.46 mm). Significant improvements in both PMA and PMP groups were also seen in clinical scores. This study showed that, compared to isolated root repair, root centralization procedures can result in significant improvement in clinical scores and MME, but the benefits appear dependent on the surgical technique. We identified two predominant techniques, and while both PMA and PMP techniques report improvement in clincal scores, the PMA technique appeared to demonstrate a more consistent reduction in MME.
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2025-11-01
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41166858
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Predicting oxcarbazepine-induced hyponatremia in adult epilepsy patients: A multicenter machine learning analysis using real-world CDM data.
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Oxcarbazepine (OXC) is a widely used antiseizure medication (ASM) associated with hyponatremia. This study aimed to assess the prevalence and risk factors for OXC-induced severe hyponatremia using machine learning (ML) models applied to multicenter real-world data standardized within the Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM). We conducted a retrospective cohort study using OMOP-CDM data from two tertiary hospitals in South Korea. Adult epilepsy patients prescribed OXC were included, and severe hyponatremia was defined as a serum sodium concentration ≤128 mmol/L. Two prediction experiments were conducted: (1) single-institution training and external validation of an XGBoost model; and (2) multicenter training and evaluation of five machine learning algorithms, including XGBoost, random forest, support vector machine, logistic regression, and naïve Bayes. SHAP (SHapley Additive exPlanations) values were used for model interpretation. Among 2253 patients, the prevalence of severe hyponatremia was 8.4%. In Experiment 1, XGBoost showed strong internal performance (AUROC 0.82) but decreased external performance (AUROC 0.72). In Experiment 2, XGBoost trained on multicenter data achieved the highest AUROC (0.83) and F1-score (0.41), outperforming other models. SHAP analysis identified key predictors including valproate use, diuretics, high OXC dosage, age, and stroke history. Additional medications such as beta-blockers, calcium channel blockers, hypnotics, and other ASMs (e.g., levetiracetam, pregabalin, lacosamide) also contributed to risk. XGBoost demonstrated robust predictive performance for OXC-induced severe hyponatremia using multicenter CDM data. SHAP-based interpretation revealed clinically relevant risk factors, supporting the implementation of personalized monitoring strategies in epilepsy care.
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2025-10-16
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41174088
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Improving timing of early neonatal hypoglycemia screening in the well-baby nursery.
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Neonatal hypoglycemia can impair neurodevelopment. Timely glucose screening, aligned with AAP guidelines, may enable prompt detection of hypoglycemia. This initiative, conducted from November 2021 to April 2023, aimed to improve the timing of screening without negatively impacting breastfeeding. Key drivers included timely recognition of at-risk status and improved adherence to the institutional protocol. Overall, 823 infants were screened. Mean age at initial glucose screening decreased by 37%, from 175 to 111 min (p < 0.001). Median (IQR) age at hypoglycemia detection reduced from 133 (107-180) to 101 (81-118) minutes (p < 0.001). Late-detected hypoglycemia episodes (detected >2 h of age) among affected infants decreased from 30 to 0% (p = 0.06). Exclusive breastfeeding and NICU transfer rates for hypoglycemia remained stable. Early recognition of risk factors, staff education, and improved team handoffs can improve timing of initial hypoglycemia screening without impacting breastfeeding or increasing maternal-infant separation.
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2025-10-31
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41199315
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Berberine and berberrubine promote the expression of CYP3A4 via enhancing the binding of nuclear receptor PXR.
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Berberine is currently co-administered with statins in clinical practice for hyperlipidemia management. This study aimed to investigate the effects of berberine and berberrubine on CYP3A4 expression and the regulatory mechanism. Using rifampicin as a positive control group, HepG2 cells were treated with different concentrations of berberine and berberrubine. Q-PCR was employed to detect the expression levels of CYP3A4 mRNA in response to the drugs, and Western blot was utilized to determine the expression of CYP3A4 and PXR proteins. Dual luciferase reporter gene assay and RNA interference technology were used to silence PXR to explore the mechanism of berberine and berberrubine regulation of CYP3A4. Compared with the blank control group, both berberine and berberrubine could induce CYP3A4 mRNA expression in a concentration-dependent manner (<i>P</i> < <i>0.05</i>). After treatment with 50 µM berberine and 60 µM berbamine for 48 h, the expression of CYP3A4 in HepG 2 cells was increased by 2.5 and 2.7 times, respectively. Berberine (10 ~ 50 µM) and berberrubine (15 ~ 60 µM) could upregulate the expression of PXR nuclear protein in a dose-dependent manner. Berberine and berbamine at different concentrations significantly upregulated the activity of the dual luciferase constructed based on PXR (<i>P</i> < <i>0.05</i>), while silencing PXR reduced the inductive effects of berberine and berbamine on CYP3A4. Berberine and berbamine at different concentrations significantly upregulated the activity of the dual luciferase constructed based on PXR (<i>P</i> < <i>0.05</i>), while silencing PXR reduced the inductive effects of berberine and berbamine on CYP3A4. Berberine and berberrubine can promote the expression of CYP3A4 protein in HepG2 cells by inducing the nuclear receptor PXR to bind to the promoter of CYP3A4. The online version contains supplementary material available at 10.1186/s40360-025-01026-7.
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2025-11-06
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41191359
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Hearing Loss, Brain Structure, Cognition, and Dementia Risk in the Framingham Heart Study.
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Age-related hearing loss is a potentially modifiable risk factor for cognitive impairment and dementia. To investigate the association of hearing loss with brain structure changes, cognitive function, and incident dementia. This cohort study included Framingham Heart Study Offspring Study participants attending their sixth quadrennial examination (1995-1998) divided into 2 partially overlapping samples. Sample 1 participants underwent brain magnetic resonance imaging and cognitive assessment at their seventh and eighth quadrennial examinations. Sample 2 included participants aged 60 years or older at pure tone average (PTA) analysis and subsequently followed up for incident dementia. The data analysis was performed between January 12, 2024, and August 24, 2025. Hearing loss. The main outcomes were changes in brain volume on MRI, cognitive performance on neuropsychological testing, and incident all-cause dementia. Multivariable linear regressions were used to compare PTA and hearing loss categories with neuropsychological measures and total cerebral, hippocampal, and white matter hyperintensity brain volumes. Cox proportional hazards regression was used to examine longitudinal associations between PTA and hearing loss categories and incident dementia. Sample 1 included 1656 participants (mean [range] age, 58.1 [29.7-85.6] years; 903 female [54.5%]), and sample 2 included 935 participants (mean [range] age, 67.6 [60.0-85.6] years; 518 female [55.4%]). Participants with mild or greater hearing loss, compared with those with no or only slight hearing loss, had significantly smaller brain volumes (β [SE], -4.10 [1.76]) and declines in executive function (β [SE], -0.04 [0.01]). Participants with at least slight hearing loss, compared with those with no hearing loss, had significant increases in white matter hyperintensity volume (β [SE], 0.02 [0.01]) and a higher risk of developing all-cause dementia (hazard ratio, 1.71; 95% CI, 1.01-2.90) over 15 years of follow-up, particularly among those with at least 1 apolipoprotein E ε4 allele (hazard ratio, 2.86; 95% CI, 1.12-7.28). This cohort study found that midlife hearing loss was associated with smaller brain volumes, accelerated worsening in executive function, and an increased risk of dementia, suggesting that it may be an early marker of brain aging and dementia risk.
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2025-11-03
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41208775
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Modular Synthesis of Diverse <i>gem</i>-Difluoroalkenes from Trifluoroacetic Anhydride via Phosphorus-Assisted Fluoride Elimination.
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Here we report a modular strategy for constructing structurally diverse <i>gem</i>-difluoroalkenes via phosphorus-assisted fluoride elimination using trifluoroacetic anhydride as the fluorine source. The protocol provides access to fully substituted architectures with unprecedented generality across alkyl, aryl, alkenyl, alkynyl, heteroatom-centered, and fused-ring groups and bioactive heterocycles (indoles, pyrimidines, glycosides), enabling downstream transformations via cycloadditions and functionalization. Mechanistic studies reveal a radical phosphorus-installation step followed by rate-determining P-F elimination.
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2025-11-10
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41168084
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Lysine demethylase 4A: from chromatin to centrosomes.
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The lysine demethylase 4A (KDM4A) remodels chromatin by histone demethylation, regulating gene expression. In this issue, Chowdhury et al. report a previously undescribed localisation for KDM4A outside the nucleus, at the pericentriolar material around the centrosome. KDM4A interacts with centrosome proteins, and its loss or inhibition leads to centrosome amplification or fragmentation, which in turn perturbs mitosis and causes genome instability. These findings suggest a link between chromatin regulation and control of centrosome number, through the regulation of KDM4A-dependent lysine methylation.
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2025-10-30
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41184967
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Targeted test evaluation: five suggestions for refining the framework for designing diagnostic accuracy studies with clear study hypotheses.
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Five years ago, Korevaar and colleagues proposed a framework for designing diagnostic accuracy studies, focusing on the definition of clear study hypotheses. This proposal filled a gap and was well received by the scientific community. In this commentary, I suggest five potential refinements. They aim at increasing the flexibility of the framework while pertaining its logical consistency. The refinements address the following five topics: (1) The relationship between minimal criteria and the choice of the null hypothesis region; (2) The potential to allow compensation between sensitivity and specificity; (3) The possibility to use other pairs than sensitivity and specificity; (4) The potential phrasing as an estimation problem; (5) The advantages of directly moving to a comparative accuracy study.
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2025-11-04
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41207044
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A coumarin-benzothiazole probe-driven multimodal aptasensing platform for label-free analysis and portable visualization of kanamycin in milks.
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Kanamycin (KANA) is an aminoglycoside antibiotic that widely adopted in foods safety and the excessive intake can cause various symptoms. Although conventional methods for KANA detection have been well-developed, they still remain challenges in real scenarios application. We here report a coumarin-benzothiazole probe and KANA aptamer-based multimodal aptasensing platform (DR1/K-apt) to realize the efficient and accurate KANA analysis in milks. The formation of DR1/K-apt can severally produce the colorimetric/fluorescent/visual signals for KANA response within 30 min, which constitute the corresponded detection manners with sensitive detection limit (0.001 mM) and wide detection linear ranges. Especially, the fluorescence of DR1/K-apt can produce the obvious green-red-green colors variation and contribute to construct a smartphone-based portable paper device (K-cPAD) to reveal the facile quantification of KANA. It will hold the potential in realizing the large-scale instrument-free and chemical labelling-free KANA detection and offer a powerful tool in antibiotics evaluation and foods safety research.
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2025-11-07
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41180176
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Elevated pre-pregnancy testosterone is associated with gestational diabetes mellitus: an observational cohort study.
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Pre-pregnancy testosterone increase may be closely related to the occurrence of gestational diabetes mellitus (GDM). Our aim is to explain the relationship between pre-pregnancy testosterone levels and the risk of GDM and provide evidence for early clinical warning. We conducted a retrospective cohort study on 4174 parturient. The exposure factor is pre-pregnancy testosterone, with the primary outcome was GDM (A1+A2) and the secondary outcome was GDM A2. We used trend testing, multivariate logistic regression models, smooth curve fitting, and age and BMI for subgroup analysis and interaction analysis to evaluate the relationship and odds ratio between different pre-pregnancy testosterone levels and GDM risk. Elevated levels of pre-pregnancy testosterone are closely related to the onset of GDM Compared with the control group, women with testosterone levels between Q4 nmol/L had an OR value of 1.76 (95% Confidence Interval: 1.38,2.25) for GDM (A1+A2). The OR value for GDM A2 is 2.26 (95% CI: 1.27,4.00). In terms of sensitivity analysis, it was also observed that elevated pre-pregnancy testosterone increased the risk of GDM, especially in the age<35 and BMI<24 groups. Pre-pregnancy testosterone had a greater effect on GDM A2, with OR values of 1.42 (95%CI: 1.04,1.94) and 1.86 (95% CI: 1.30,2.66). Pre-pregnancy testosterone testing is associated with the risk of developing GDM, and women age<35 or BMI<24 need to pay more attention to pre-pregnancy testosterone. Pre-pregnancy testosterone can serve as a potential biomarker for risk stratification of GDM.
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2025-01-01
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41193350
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[Costs of informal caregiving for people with cognitive impairment: A cost study based on the Digital Dementia Registry Bavaria (digiDEM Bayern)].
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Informal care costs account for the largest share of the total costs of dementia. The informal care costs of dementia have been well researched in Germany, but the group of family caregivers of people with MCI ("mild cognitive impairment") has not been taken into account so far. The aim of this study is the evaluation of care time spent by family caregivers of people with cognitive impairment according to the severity of the disease and to estimate informal care costs. The data is based on the multicenter, prospective registry study "Digital Dementia Regustry Bavaria - digiDEMBayern" (German title: "Digitales Demenzregister Bayern - digiDEM Bayern"). Information on informal care time was collected using the "Resource Utilization in Dementia Lite (RUD-Lite)" instrument. Informal care costs were calculated using the opportunity cost approach. Sensitivity analyses were used to determine a high and a low cost estimate and to compare them with each other. Severity-related differences were assessed using variance analyses. The survey results of 445 people with cognitive impairment and their informal caregivers were evaluated. The average care time to support activities of daily living significantly increased with greater severity (p = 0.005). The average cost of informal caregiving was between 15,057 and 30,994 EUR for people with mild cognitive impairment, between 19,785 and 38,747 EUR for people with mild dementia, and between 23,709 and 48,451 EUR for people with moderate dementia. Several earlier studies found an increase in the costs of informal caregiving with increasing cognitive decline in Germany. However, these studies differ in the methodologies used. There are various reasons why comparatively higher costs of informal care have been calculated in the present study. It is likely that the annual costs of informal caregiving are in the range described, depending on the level of severity. The results indicate that people caring for family members with MCI bear a significant burden and that this leads to high social costs. The indirect costs of dementia increase the burden on society also from an economic perspective.
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2025-11-04
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41170807
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Maternal and neonatal outcomes of ultrasound-guided percutaneous nephrostomy for symptomatic hydronephrosis in pregnancy: a retrospective cohort study.
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To evaluate the maternal and neonatal outcomes of pregnant patients who underwent ultrasound-guided percutaneous nephrostomy for the management of symptomatic hydronephrosis. This retrospective cohort study evaluated 85 pregnant patients with symptomatic hydronephrosis (≥ Grade 2) managed at a tertiary center between January 2020 and February 2025. Participants were stratified into ultrasound-guided PCN (n=43) and conservative management (n=45) groups. The primary outcome of this study was to evaluate the safety and efficacy of ultrasound-guided PCN in pregnant patients with symptomatic hydronephrosis. Demographic characteristics were similar between groups. Abdominal pain was more common in the conservative group (45.5 % vs. 26.8 %, p=0.062), while other clinical and laboratory parameters showed no significant differences. Antibiotic use differed significantly (p=0.016), though urine culture results were comparable. Pregnancy and neonatal outcomes, including gestational age at delivery, birth weight, Apgar scores, cesarean delivery rates, and neonatal intensive care unit (NICU) admission rates, did not differ significantly between groups (all p>0.05). Kaplan-Meier survival analysis demonstrated no statistically significant difference in cumulative live birth rates between the PCN and conservative treatment groups (log-rank test, p=0.665), with hazard ratios indicating comparable reproductive outcomes over time. This study demonstrates that ultrasound-guided PCN is a safe and effective intervention for managing symptomatic hydronephrosis during pregnancy, with favorable maternal and neonatal outcomes. Further prospective studies with larger cohorts are warranted to validate these findings and refine clinical guidelines.
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2025-11-03
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41179665
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Concurrent esophageal squamous cell carcinoma with gastric mucosa-associated lymphoid tissue lymphoma: a case report.
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Double primary malignant tumors are infrequently encountered, with esophageal squamous cell carcinoma (ESCC) co-occurring with malignancies in other organs, representing a rare clinical entity. The concomitant presence of ESCC and lymphoma is even more uncommon, posing substantial diagnostic and therapeutic challenges. A 76-year-old Han Chinese man presented with dizziness, dysphagia, and vomiting. Computed tomography suggested a potential esophageal neoplasm. Gastroscopy identified an ulcerated esophageal mass, accompanied by altered gastric body morphology and branching changes. Histopathological examination of biopsied esophageal and gastric mucosa confirmed ESCC concurrently with gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The patient declined surgical intervention and succumbed 13 months after diagnosis. The simultaneous occurrence of ESCC and gastric MALT lymphoma remains exceedingly rare. In ESCC cases, the potential for coexisting malignancies in the pharynx, stomach, or other sites warrants consideration. This report documents the first known case of ESCC coexisting with gastric MALT lymphoma, contributing to the current understanding of diagnosis and management strategies in lymphoma-associated ESCC cases.
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2025-01-01
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41185107
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EBV-associated Vulvar Ulcer Following Receptive Oral Sex in an Adolescent: A Case Suggesting Possible Sexual Transmission.
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We report a case of Epstein-Barr virus (EBV)-associated vulvar ulcer in a 17-year-old girl, with EBV DNA confirmed by polymerase chain reaction (PCR) in both blood and ulcer swab. A history of receptive orogenital exposure raises the possibility of local viral inoculation. This case highlights the value of EBV testing in adolescents presenting with acute genital ulceration of unclear etiology.
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2025-11-04
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41183572
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mRNA nanomedicine reprograms the cell cycle to increase the effectiveness of targeted therapy for HER2-low breast cancers.
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Over 70 % of breast cancer patients present with tumors exhibiting low or undetectable HER2 expression, making them largely unresponsive to current HER2-targeted therapies. To address this, we developed an innovative lipid nanoparticle (LNP)-based mRNA nanomedicine that reprograms tumor cell cycle by restoring expression of both HER2 and p53 genes, two key regulators of tumor progression and treatment resistance. This combination strategy induces synergistic tumor cell death, particularly in p53-deficient, HER2-low/negative breast cancers. Importantly, this approach sensitized previously unresponsive tumors to trastuzumab, a HER2-targeted antibody. In vivo studies using HER2-low patient-derived xenograft (PDX) and HER2-negative cell-derived xenograft (CDX) models further demonstrated robust tumor regression. This novel mRNA nanomedicine represents a transformative therapeutic strategy, offering a promising solution for patients with HER2-low cancers who currently have limited treatment options.
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2025-11-01
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41211727
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Reactivity of Nanoconfined Water Is Modulated by the Properties of Confining Materials.
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The autoionization of water, a fundamental process in aqueous chemistry, is profoundly altered under nanoconfinement. The properties of the confining material determine the layer dependence of autoionization, dictating whether reactions are stabilized at the interface or in the subsurface. Under weak water-wall interactions, hydroxide is destabilized at the interface, leading the reaction to proceed preferentially in the subsurface. Conversely, under strong water-wall interactions, the interfacial and subsurface states are nearly isoenergetic, thereby diminishing the selectivity between the two regions. This contrast arises from confinement-enforced coordination motifs where hydronium remains tri-coordinated across environments, while hydroxide is restricted to tetra-coordination at the interface but adopts hypercoordinated states in the subsurface. Mechanical flexibility of the confining framework further modulates the overall thermodynamics by reducing the entropic penalty, as water molecules can explore a broader configurational space compared to rigid pores. These findings establish how layer-specific solvation and wall flexibility govern confined-water reactivity, providing molecular-level design principles for engineering dynamic nanoscale interfaces in catalysis, energy storage, and molecular separations.
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2025-11-10
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41194049
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Surgical outcomes of Ahmed valve implantation with mitomycin C in glaucoma with and without high myopia.
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This study aimed to assess the surgical outcomes of Ahmed glaucoma valve (AGV) implantation in high myopic eyes (axial length [AL] of ≥ 26.0 mm) and to determine whether high myopia independently poses a risk of surgical failure. We retrospectively reviewed 68 eyes from 59 patients with refractory glaucoma who underwent AGV implantation. Eyes were categorised into high myopia (23 eyes, 33.8%) and control (45 eyes, 66.2%) groups. The primary outcome was the surgical success rate, defined as postoperative intraocular pressure (IOP) of 6-21 mmHg or a ≥ 20% reduction from baseline. Surgical success was further classified into criterion A (postoperative IOP ≤ 21 mmHg) and criterion B (postoperative IOP ≤ 15 mmHg). Surgical success rates were estimated using Kaplan-Meier analysis, and risk factors for surgical failure were identified via Cox proportional hazards modelling. At 1 and 2 years, surgical success was significantly higher in the control group according to criterion A (p = 0.013 and 0.043, respectively). Based on criterion B, the control group also showed better surgical success, although the difference did not reach statistical significance. (p = 0.051). Postoperative IOP was lower in the control eyes throughout all postoperative periods, and the difference reached statistical significance at 6 months (p = 0.017). An AL ≥ 26 mm was a significant risk factor for surgical failure under both criterion A (hazard ratio [HR] = 8.30, p = 0.026) and criterion B (HR = 6.26, p = 0.009). AGV implantation in glaucoma eyes with high myopia showed lower surgical success compared to those without high myopia. Longer AL is a significant risk factor for surgical failure, underscoring the importance of careful monitoring after AGV implantation in such cases.
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2025-11-05
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41178751
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TGFβ Participation in the Remyelination Process Through Microglial Modulation and Oligodendrocyte Maturation.
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Central nervous system (CNS) diseases occur in the context of inflammation and demyelination. Demyelination is a pathological process in which myelin sheaths are lost from around axons, while remyelination is the restoration of myelin sheaths by oligodendrocytes. TGFβ is an anti-inflammatory cytokine that participates in the immune response, favors the oligodendroglial cell fate of adult neural precursor cells, and induces oligodendrocyte precursor cell (OPC) differentiation and maturation. To evaluate TGFβ participation in remyelination, in vivo experiments were performed in control and cuprizone (CPZ)-treated rats intracranially injected (IC) with either TGFβ or vehicle and analyzed after 7 days, or intraperitoneally injected (IP) TGFβ before toxin removal from the diet. After IC, TGFβ induced an increase in phagocytic microglia in control and demyelinated animals and in MAG+ cells in demyelinated animals. Likewise, IP TGF in CPZ-demyelinated animals showed lesser microgliosis and higher IL10 transcript levels in TGFβ-treated demyelinated animals. These anti-inflammatory effects coincided with an increase in myelin-associated glycoprotein (MAG)+ cells and MAG transcript expression. On the other hand, in vitro experiments were performed on primary microglial cultures and OPCs. In microglial cultures, TGFβ treatment reduced iNOS, IL1β, TNFα, and IL10 transcript levels and increased those of Arg1. TGFβ also reduced microglial phagocytic capacity after LPS exposure. In OPC cultures, TGFβ produced no changes in platelet derived growth factor receptor alpha (PDGFRα)+ and myelin basic protein (MBP)+ cells but promoted morphological complexity in OPCs and mature oligodendrocytes. These results suggest that TGFβ might have a positive action in remyelination by modulating microglial reactivity and promoting OPC maturation.
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2025-01-01
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41200631
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The Significance of Emergency Surgical Operations for Severe Elderly Patients Considering Medical Costs and Activities of Daily Life.
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Purpose The global population is aging rapidly, and physicians increasingly face challenges in determining the appropriateness of emergency surgery for elderly patients. This study aimed to evaluate the clinical significance of emergency operations in elderly patients. Methods This retrospective clinical study included patients transferred to the emergency department of Gunma University Hospital and admitted to the intensive care unit following emergency surgery between January 2013 and December 2019. Patients were categorized into three age groups: 18-64 years (Group Y), 65-84 years (Group M), and ≥85 years (Group E). Clinical courses, including activities of daily living (ADL), were compared across groups. The primary outcomes were hospital mortality and the proportion of patients discharged directly home; secondary outcomes included additional clinical characteristics. Results A total of 84 patients were included: 30 in Group Y, 42 in Group M, and 12 in Group E. Both preoperative and postoperative ADL scores were significantly lower in Group E. Medical costs did not differ significantly among the groups. Although hospital mortality was highest in Group E, the difference was not statistically significant. However, the proportion of patients discharged directly home was significantly lower in Group E. Conclusions Emergency operations in patients aged ≥85 years may achieve outcomes comparable to those in younger patients; however, the total treatment period is likely to be prolonged due to significantly reduced postoperative ADL.
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2025-10-01
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41173734
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Seeing More, Treating Smarter: Role of Long-axial Field-of-view PET/Computed Tomography in the Evolution of Theranostics.
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Long-axial field-of-view (LAFOV) PET/computed tomography has the potential to redefine the role of molecular imaging in theranostics by making multiparametric whole-body imaging and predictive dosimetry more clinically feasible. Compared to conventional PET systems, LAFOV scanners provide dramatic gains in sensitivity and coverage, allowing dynamic acquisitions, delayed imaging, and dual-tracer protocols within clinically feasible workflows. These advances supply the quantitative data required for physiologically based pharmacokinetic modeling and the creation of theranostic digital twins, supporting true personalization of radiopharmaceutical therapy.
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2025-10-30
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41174827
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Next-generation specimen digitization: capturing reflectance spectra from the world's herbaria for modeling plant biology across time, space, and taxa.
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Spectral reflectance measured from herbarium specimens represents a potentially vast source of information relevant to plant taxon identification and functional traits, which has inspired many laboratories world-wide to initiate next-generation spectral digitization from specimens. Combining these datasets into a coordinated global database would generate new capacity to model plant traits globally, enabling connection with remote sensing and ecological and biosphere models, as well as reconstruction of trait evolution. However, coordination is needed to avoid downstream problems in data aggregation due to variation in data standards and technical specifications of the instruments, optical setups, or measurement protocols. The International Herbarium Spectral Digitization (IHerbSpec) working group has initiated a globally collaborative program, outlining the central issues to address in establishing protocols, standards, and best practices, and proposing next steps. This collaborative effort will allow generation of replicable spectral reflectance data from plant specimens housed in herbaria around the world within ongoing digitization programs following community-defined standards and Findable, Accessible, Interoperable, and Reusable (FAIR) principles.
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2025-10-31
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41172029
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[Not Available].
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Introducción: La depresión es el principal trastorno mental en América Latina. Su etiología es multifactorial, abarcando desde factores genéticos, sociodemográficos, culturales e incluso ambientales. Se ha evidenciado en algunos estudios que el vivir en regiones de gran altitud puede estar relacionado con la depresión. Por lo que este estudio tiene por objetivo determinar la correlación entre altitud y la incidencia de episodios depresivos en el Ecuador. Materiales y métodos: Estudio analítico transversal de las bases de datos de los egresos hospitalarios en el Ecuador de los años 2018 al 2022. Se estimó riesgo relativo, correlación de Pearson y se realizó regresión lineal para evaluar asociación. Resultados: Se observaron 6460 episodios depresivos en los 5 años de estudio. Las provincias ubicadas a gran altitud (≥1500 m.s.n.m.) obtuvieron las mayores incidencias acumuladas por 100 000 habitantes. Estas provincias son Tungurahua (81,4), Pichincha (68,8), Chimborazo (63,8), Imbabura (55,8) y Bolívar (51,1), respectivamente. El riesgo relativo de residencia en gran altitud fue de RR=2,67 (IC 95 %=2,54 - 2,81, p < 0,001), mientras que en la regresión lineal entre incidencia acumulada por 100 000 y la altitud se obtuvieron r=0,78, r2=0,61 y en la variable independiente altitud t=5,84, p < 0,001. Conclusión: Se determinó una correlación positiva entre la residencia en gran altitud y la incidencia de episodios depresivos, pero a causa de las limitaciones de esta investigación se requieren de otros estudios para corroborar esta asociación, ya que los resultados pueden estar influenciados por otros factores que no se consideraron.
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2025-10-10
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41203090
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Impact of microplastics and nanoplastics on human health: Mechanistic insights and exposure pathways.
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Microplastics (MPs) and nanoplastics (NPs) have emerged as critical environmental contaminants with potential adverse effects on human health. This review examines the various ways MPs and NPs can be spread in the environment and their potential impact on humans. They can be introduced into the environment through multiple sources, like synthetic textiles, cosmetics, packaging, and industrial processes. These particles enter the human body through ingestion, inhalation, and skin contact, and they deposit in various tissues, including the lungs, kidneys, and gastrointestinal tract. Additionally, they can cross embryonic layers and reach the placenta. They can cause inflammation, oxidative stress, metabolic disorders, genotoxicity, and immunotoxic effects upon interaction, as confirmed by in-vivo and in-vitro studies. Furthermore, long-term exposure to MPs and NPs causes various complications to the human body, including metabolic disorders or even the development of cancers. Despite the presence of much evidence, a significant gap remains in fully understanding the mechanism of toxicity posed by MPs and NPs exposure and its long-term health outcomes. There is an urgent need for extensive investigations and improvement in standardized methods to evaluate the human health impact of MPs and NPs. This review explores current evidence on exposure pathways, bioaccumulation mechanisms, and health outcomes and identifies critical knowledge gaps.
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2025-11-05
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41202742
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Global recreational consumption of non-native inland fish: higher economic benefits, but lower nutritional value and climate resilience.
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Inland recreational fisheries are globally significant leisure pursuits, with well-documented benefits to human health and well-being, but also one of the principal drivers of non-native fish introductions to enhance fishing opportunities, whether for sport or sustenance. In this study, we assess the relative reliance of global inland recreational fisheries on non-native versus native species for harvest. We further examine how this reliance varies by economic and nutritional value as well as the climate vulnerability of the species involved. We demonstrate that, of the 1,325,851 t of inland recreational fishes recreationally harvested for consumption worldwide in 2021, non-native fish were a small proportion (4 %; 53,651 t). On a global scale, non-native fish contributed a net positive 38.2 % economic value to inland recreational harvest. However, they also contributed a net negative -21.9 % nutritional value to inland recreational harvest. Non-native fishes were also more climate vulnerable (i.e., higher average climate vulnerability index values) and thus proportionally increased overall estimates of climate vulnerability with a net positive of 70.9 %. Our results quantitatively demonstrate that non-native species play a more important role in inland consumptive recreational fisheries than their mere harvest volume would suggest. However, many nuances were seen on the continent and country scale, which reflect the complexity of fisher behavior, fish distribution and socio-economic factors. Our findings help unravel the complex effects of non-native species on human activities and underscore the need to evaluate their global impacts holistically.
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2025-11-06
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41176604
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The influence of incorporation of hydroxyapatite/collagen nanocomposite into glass ionomer cement on surface roughness, microhardness, and fluoride-ion release potential.
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To investigate the effect of incorporation of 5 and 10 weight% of hydroxyapatite /collagen (HA/Col) nanocomposite with different ratios (50:50) and (70:30) to conventional glass ionomer cement (C-GIC) on surface roughness, microhardness, and fluoride-ion release. Seventy-five specimens were prepared using split Teflon mold (5 mm in diameter and 2 mm in thickness) and were randomly assigned to 5 different groups. Group I: control group of C-GIC, Group II: GIC modified with 5% HA/Col (50:50), Group III: GIC modified with 5% HA/Col (70:30), Group IV: GIC modified with 10% HA/Col (50:50), Group V: GIC modified with 10% HA/Col (70:30). The specimens were kept in deionized (DI) water and incubated at 37 °C.The DI water in each container was changed on the 1st, 7th, 14th, and 28th days. Fluoride ion release was assessed using the SPADNS colorimetric technique. Afterwards, a surface profilometer and a Vickers hardness tester were used to assess surface roughness and microhardness. Moreover, micromorphological analysis was assessed using SEM-EDX mapping. Regarding fluoride-ion release, mixed linear model revealed significant increase of fluoride-ion release in the 4 experimental groups compared to control one (p < 0.0001). Regarding surface roughness, and microhardness, one-way ANOVA test revealed a significant increase of surface roughness of experimental group of 10% HA/Col (50:50) compared to rest of groups, and significant increase of surface microhardness of all experimental groups compared to control one. Incorporation of HA/Col nanocomposite into C-GIC cement showed promising improvements in surface hardness and fluoride ion release.
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2025-11-01
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41164613
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Influence of Polishing Systems on Surface Roughness of Lithium Disilicate Ceramics Following Dental Bleaching.
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The alteration of surface texture of lithium disilicate materials through the application of carbamide peroxide gels, which are frequently utilized as home bleaching agents, presents significant implications that remain contentious, and the enhancement of this phenomenon via polishing techniques is additionally subject to skepticism. The objective of the study was to systematically assess the impact of bleaching and polishing protocols on the surface roughness of lithium disilicate. A total of 28 IPS e.max press discs were systematically allocated to two distinct groups. Group A served as the control cohort, while Group B constituted the experimental cohort. In the case of Group B, the bleaching agent was administered for duration of 20 minutes daily over the course of 14 days. The surface roughness of each disc was quantified prior to and following the application of the bleaching agent, as well as subsequent to the polishing intervention. In comparing the post-bleaching results of Group B to those of Group A, statistical evaluation indicated that while the roughness average (Ra) exhibited a marginal elevation following the bleaching cycles and after the polishing process, this observed increase did not achieve statistical significance (<i>P</i> > 0.05). The surface roughness of IPS e.max press discs was not significantly affected by home bleaching or polishing.
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2025-09-01
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41196708
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How digital reading habits shape reading motivation and comprehension over time: Longitudinal associations in primary school.
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Nowadays, children's reading habits extend beyond traditional printed texts, embracing new practices and forms through digital devices. The influence of such new digital reading habits on reading motivation and comprehension development remains largely underexplored. This study aimed to explore reciprocal causal paths between digital reading habits, reading comprehension and intrinsic reading motivation. To do so, we analyzed longitudinal data of 908 Spanish students from Grades 4 to 6. We estimated random-intercept and cross-lagged panel models to examine long-term associations between our main variables. Results revealed null causal paths between digital reading habits and reading comprehension for both leisure and academic purposes. After controlling for autoregressive effects and considering only within-person variance, one significant path remained from academic digital reading habits in Grade 5 to decreased intrinsic reading motivation in Grade 6. Our study provides new insights about the role of digital reading habits in the development of reading comprehension and intrinsic reading motivation in primary school students. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
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2025-11-06
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41211684
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Reducing internalized HIV stigma with Intervention Mapping: the design, implementation, and evaluation of RESET (RESilience and Empowerment Training).
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HIV is a highly stigmatized condition, and negative beliefs about HIV and people with HIV are frequently internalized. This paper describes how we designed, implemented, and evaluated RESET, an intervention aiming to reduce internalized HIV stigma among people with HIV in the Netherlands. This face-to-face, three-session workshop series was designed, implemented, and evaluated with <i>Intervention Mapping,</i> a systematic approach to behavior change that uses theory and evidence, as well as participatory processes, in the planning of interventions. <i>Intervention Mapping</i> comprises six steps: (1) conducting a needs assessment and drafting a Logic Model of the Problem; (2) specifying intervention outcomes and objectives, and drafting a Logic Model of Change; (3) designing the intervention by selecting theory and evidence-based methods for behavior change and then developing their practical applications; (4) producing and pre-testing the intervention; (5) planning for implementation; and (6) planning process and effect evaluations. For each step, we describe the tasks involved and how we approached each task as we designed, implemented, and evaluated RESET. By transparently reporting how RESET was developed, we illuminate success and challenges and demonstrate how <i>Intervention Mapping</i> can be leveraged to develop effective interventions for reducing stigma, including internalized HIV stigma.
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2025-11-10
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41210678
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Aneurysmal Coronary Artery Disease: A Contemporary and Comprehensive Review.
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Coronary artery aneurysm (CAA) is a focal enlargement of the coronary artery exceeding 1.5 times the diameter of the adjacent normal segment of the vessel. The reported prevalence of CAA varies widely from 0.2 to 10%, with male predominance and a predilection for the right coronary artery. Atherosclerosis is the main cause in adults and Kawasaki disease in children. While often asymptomatic, CAA may present with angina, myocardial infarction, or possible fatal complications such as rupture, compression of adjacent cardiopulmonary structures, thrombus formation, and distal embolization. CAA is usually an incidental finding during coronary angiography; however, advancements in cardiac imaging have enhanced the detection and characterization of CAA. Coronary computed tomography angiography and magnetic resonance angiography offer alternatives to traditional approaches with high-resolution images that can help with risk stratification and management planning. Management varies based on the size, location, complications, and presence of symptoms. It includes medical therapy, percutaneous intervention, and surgical approach. In this paper, we aim to provide a comprehensive review of current knowledge of CAA and recent advances in its diagnosis and management.
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2025-12-01
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41187863
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Correlates of antibiotic use in U.S. adults: An analysis of medical expenditure panel survey data, 2017-2022.
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To identify sociodemographic and health-related correlates of antibiotic use in U.S. adults and determine whether racial/ethnic and regional disparities persisted throughout and after the COVID-19 pandemic. Using data from the Medical Expenditure Panel Survey (2017-2022) for 118,110 U.S. adults aged 18 years or older, Poisson regression was used to quantify the associations of interest via prevalence ratios (PR) and 95 % confidence intervals (CI). Effect modifications of race/ethnicity and region with pandemic periods were evaluated. The prevalence of antibiotic use was 14.3 %. In adjusted analyses, adults aged 65 or older (PR = 1.27, 95 %CI:1.20, 1.35), women (PR = 1.45, 95 %CI:1.40, 1.51), and privately insured individuals (PR = 1.67, 95 %CI:1.50,1.87) had higher antibiotic use than their counteraprts who were aged 18-34 years, men, and uninsured. Higher education was associated with a higher probability of antibiotic use. Hispanic (PR = 0.65, 95 %CI:0.60, 0.71), Black (PR = 0.61, 95 %CI: 0.57, 0.65), and Asian adults (PR = 0.54, 95 %CI:0.47, 0.62) use less antibiotics than White adults. Antibiotic used was greater in the South (PR = 1.18, 95 %CI:1.09, 1.28) and Midwest (PR = 1.12, 95 %CI:1.03, 1.22) than the Northeast. Chronic bronchitis showed the strongest association (PR = 1.34, 95 %CI:1.23, 1.46). No interactions of race/ethnicity and region with pandemic period were observed (p-values>0.12). Given the observed antibiotic use disparities, stewardship efforts require strategies targeting specific groups to address inequities.
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2025-11-02
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41188976
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Engineering hypoimmune stem cell-derived beta cells.
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In type 1 diabetes (T1D), autoimmune targeting destroys insulin-producing β cells in the pancreas, creating a chronic state of insulin deficiency. Islet transplantation presents a regenerative cell therapy approach that can re-establish insulin production and intrinsic glycemic control. However, islet transplantation is currently limited by a lack of cadaveric human islet donors and a requirement for life-long immune suppression following transplant. Developments in stem cell maturation and differentiation protocols have enabled production of insulin-producing cells 'on demand', thereby addressing the pancreatic donor tissue shortage. Continued reliance on immune suppression to avoid graft rejection, however, can result in opportunistic infection and malignancy, thus remaining a major obstacle for wide-spread application of insulin-producing β cell transplantation. As such, there has been significant interest in identifying alternative strategies for avoiding graft rejection without immune suppression including encapsulation and co-transplantation of accessory immunomodulating cells. However, these approaches are limited by incomplete immune isolation as well as concerns over maintenance of effector function and graft survival in vivo, respectively. Genetically engineering hypoimmune stem cell-derived β cells has thus emerged as a promising strategy for improving islet transplantation outcomes. These approaches leverage our understanding of pathways involved in immune regulation to selectively protect the transplanted insulin-producing cells without affecting systemic immune function. This review will summarize recent bioengineering approaches for generating hypoimmune stem cell-derived β cells. It will also discuss relevant safety concerns and potential genetic targets for future investigation that take inspiration from the development of immune evasive primary islets and chimeric antigen receptor (CAR) T cells.
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2025-11-04
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41197372
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Decadal changes in California's temperate mesophotic reef invertebrate community through the 2014-2016 northeast Pacific marine heatwave.
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The 2014-2016 northeast Pacific marine heatwave (MHW) disrupted marine ecosystems in California, with well-documented impacts on kelp reef ecosystems, and deep reef fish assemblages. However, no studies have assessed the direct or indirect impacts on sessile benthic reef invertebrates inhabiting mesophotic rocky reefs (>30 m deep), despite their critical role in biodiversity and ecosystem function. Given that much of California's rocky reefs lie within mesophotic depths, understanding their responses to climate-driven disturbances is a high priority. Using remote operated vehicles surveys conducted from 2005 to 2021 across marine protected areas (MPAs) and habitat-matched reference sites, we quantified changes in sessile invertebrate abundance, both independently and in relation to urchin presence, during and after the MHW. Community responses varied across a five-degree latitudinal gradient (33.87°- 38.97°N), with no consistent differences attributable to MPA designation. Sponges and California hydrocorals increased regionally, while red and purple gorgonians, elephant ear tunicates, and sea whips declined during the MHW and remained suppressed five years later. Although surface warming reached mesophotic depths at some sites, temperatures remained within typical ranges, suggesting the MHW event may not be the primary driver of the observed changes. Instead, broader ecosystem perturbations likely facilitated red sea urchin expansion into mesophotic depths from 2015 onwards. Their presence was associated with declines in several species, representing a potential indirect pathway through which this climate disturbance affects mesophotic assemblages. These findings highlight the need for depth-resolved monitoring to assess changes in this understudied ecosystem and to identify mesophotic refugia at thermally stable sites.
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2025-10-22
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41165237
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TRPC6 effects on albumin permeation, nephrin shedding, and apoptosis in podocytes: Role of calcineurin and metalloproteases.
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The effects of TRPC6 activation for various periods of time on three classes of functional outputs were examined in cultured podocytes: albumin permeation across a confluent layer; changes in nephrin dynamics; and cell death. Albumin permeation in transwell assays was significantly increased within 1 h in response to the activation of formyl peptide receptors (FPR), but the TRPC6 inhibitor SAR-7334 had no effect on this response, and 1 h or 24 h exposures to the TRPC6 activator PPZ2 did not increase albumin permeation. Direct TRPC6 activation for 24 h evoked an increase in shedding of nephrin ectodomains into the surrounding media, accompanied by an increase in matrix metalloprotease-7 (MMP-7). These effects were blocked by the calcineurin inhibitor cyclosporin A (CsA), as well as by Batimastat, a broad-spectrum inhibitor of metalloproteinases including MMP-7. TRPC6 activation for 24 h also evoked an increase in occludin abundance but had no effect on the abundance of podocin. Finally, TRPC6 activation for 72 h, but not for 24 h, evoked an increase in apoptotic cell death based on increases in cleaved caspase-3. This effect was blocked by both SAR-7334 and CsA. TRPC6 activation did not induce pyroptosis based on the measurement of cleaved gasdermin D.
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2025-11-01
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41176318
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Cannabis use among young adults with acute coronary syndrome: impact on initial presentation and long-term prognosis.
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Cannabis consumption has increased among young adults, but its long-term cardiovascular impact remains unclear. This study assessed the association between cannabis use at admission for acute coronary syndrome (ACS) and long-term prognosis. A retrospective, single-centre cohort included patients under the age of 45 years admitted for ACS between 1 January 2010 and 1 March 2025, all of whom reported current tobacco use at admission. Based on urinary testing at admission, patients were classified as cannabis users or non-users. The primary endpoint was major adverse cardiovascular events (MACE), a composite of death, stroke, recurrent myocardial infarction, arrhythmia or heart failure-related events. A propensity-weighted analysis adjusted for socioeconomic and cardiovascular risk factors was conducted. Weighted survival curves were plotted, and a Cox model truncated at 6 years was used to estimate the HR for MACE associated with cannabis use. Among 188 included patients, 77 (41.0%) were cannabis users and 111 (59.0%) non-users. The median follow-up was 2.93 (0.45-5.53) years. Weighted Kaplan-Meier curves differed significantly (Fleming-Harrington p=0.002), with a higher cumulative incidence of MACE among cannabis users. In the inverse probability of treatment weighting Cox model, cannabis use was associated with a higher hazard of MACE (HR 2.52, 95% CI 1.05 to 6.02; p=0.04). Cannabis users also had higher peak troponin levels, higher leucocyte counts and a greater use of postprocedural anticoagulation (all p<0.05). Cannabis use in young adults with ACS was associated with a 2.5-fold higher hazard of MACE over 6 years, highlighting the need to take cannabis use into account in cardiovascular care pathways.
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2025-10-31
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41182345
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Effect of renal denervation on the lipid profile in patients with or without coronary artery disease.
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Sympathetic overactivation plays a critical role in the pathophysiology of various conditions, such as arterial hypertension, chronic kidney disease, coronary artery disease (CAD), diabetes, metabolic syndrome, and dyslipidemia. Initially developed for hypertension management, renal denervation (RDN) has also been associated with metabolic improvements. Preclinical studies in rodent models suggest that RDN may improve lipid profiles by reducing sympathetic activity. This study analyses the effect of RDN on lipid profiles in hypertensive patients with or without CAD. This analysis includes 122 hypertensive patients with (n = 30) or without CAD (n = 92). All patients underwent radiofrequency, ultrasound, or alcohol-injection-based RDN. Fasting lipid profile, including total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and non-HDL levels was measured at baseline and 6 months after RDN in parallel to office and 24-h ambulatory blood pressure (BP). Six months after RDN, the total cohort showed significant lipid profile improvements. The total cholesterol levels decreased by 10.3 ± 26.3 mg/dL (p < 0.001), LDL by 7.0 ± 20.4 mg/dL (p < 0.001), and triglycerides by 30.7 ± 69.4 mg/dL (p < 0.001), while non-HDL cholesterol levels declined by 7.6 ± 26.3 mg/dL (p = 0.002). These changes were independent of BP reduction. In patients with CAD, total cholesterol levels declined by 21.7 ± 29.1 mg/dL (p < 0.001), triglycerides by 40.7 ± 80.0 mg/dL (p = 0.009), LDL by 15.2 ± 22.0 mg/dL (p < 0.001), HDL by 2.8 ± 4.7 mg/dL (p = 0.003), and non-HDL by 15.0 ± 34 .8 mg/dL (p = 0.021). Reductions in total cholesterol and LDL were greater in CAD than in non-CAD (p = 0.011 and p = 0.006). We observed a significant improvement in lipid profiles in hypertensive patients with CAD after RDN. This improvement may represent an additive benefit of RDN in hypertensive patients with CAD.
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2025-11-03
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41173959
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From performance to prediction: extracting aging data from the effects of base load aging on washing machines for a machine learning model.
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The standard testing of washing machine performance faces reliability challenges, which stem from the uncontrollable degradation of base load. This study provided a quantified standard for base load age to enhance the reliability and stability of the washing machine performance testing process. First, the impact of base load aging on the cleaning performance and water extraction performance was investigated. Simultaneously, the changes in reflectance of the base load were recorded. Then, MLR and ANN models were developed using the remaining moisture content and reflectance of the base load to predict base load age. It was found that the water extraction performance is more easily affected by the aging of the base load than the cleaning performance. In addition, ANN has better performance in predicting base load age, resulting in an R<sub>c</sub><sup>2</sup> of 0.978, RMSEC of 9.295 h, and R<sub>cv</sub><sup>2</sup> of 0.972 h, RMSECV of 10.639 h for the front-loading washing machine, and R<sub>c</sub><sup>2</sup> of 0.958, RMSEC of 12.948 h, and R<sub>cv</sub><sup>2</sup> of 0.940, RMSECV of 15.572 h for the top-loading washing machine. This study establishes a theoretical foundation for optimizing base load age regulation. Further study could expand the sample size to enhance the robustness and generalizability of the proposed method.
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2025-10-31
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41166697
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In Vitro Characterization of the Aromatic SAM-Dependent C-Methyltransferase NapB5.
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Aromatic polyketide synthase (PKS) products undergo diverse tailoring reactions in the biosynthesis of natural products. <i>S</i>-Adenosyl-l-methionine (SAM)-dependent C-methyltransferases (C-MTs) play a key role in this diversification. In the biosynthesis of napyradiomycins, the C-MT NapB5 from <i>Streptomyces aculeolatus</i> catalyzes the C2 monomethylation of an 1,3,6,8-tetrahydroxynaphthalene (T<sub>4</sub>HN) building block. Biochemical characterization reveals that NapB5 exhibits chemoselective C-dimethylation activity in vitro, accepting both T<sub>4</sub>HN and its oxidized derivative flaviolin as substrates. Structure-guided mutagenesis and docking studies suggest that precise substrate positioning governs the enzyme's regio- and chemoselectivity. The proximity between the nucleophilic carbon and the SAM methyl donor is crucial for this selectivity. Furthermore, comparative gene cluster analysis identifies homologous C-MTs in other actinomycetes, underscoring their role in diversifying naphthoquinone-based meroterpenoid natural products.
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2025-10-30
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41208783
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Dual-Mode Thermal Response of Visible/NIR Emission in Er<sup>3+</sup>-Doped Layered Perovskite via Modulating Thermally Induced Oxygen Vacancies and Cross Relaxation.
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Overcoming thermal quenching remains a pivotal challenge for the practical application of upconversion luminescence (UCL) materials. Herein, a novel UCL material based on Er<sup>3+</sup>-doped layered perovskite oxyhalide Bi<sub>4</sub>Ti<sub>0.5</sub>W<sub>0.5</sub>O<sub>8</sub>Cl is demonstrated to exhibit a unique dual thermal-response behavior: conventional thermal quenching of green/red emissions alongside remarkable thermally enhanced near-infrared (NIR) UCL within the temperature range of 293-493 K. Under 980 nm excitation, the NIR UCL intensity (<sup>4</sup>I<sub>9/2</sub> → <sup>4</sup>I<sub>15/2</sub>) in Bi<sub>4</sub>Ti<sub>0.5</sub>W<sub>0.5</sub>O<sub>8</sub>Cl:10%Er<sup>3+</sup> at 493 K reached 133-fold that at 293 K. The opposite thermal response is attributed to the synergistic effects of tunable oxygen vacancy concentrations and optimized cross-relaxation processes at elevated temperatures. By leveraging the opposing thermal responses of Er<sup>3+</sup> emissions, an ultrahigh absolute sensitivity of 72.26% K<sup>-1</sup> was achieved at 493 K based on the fluorescence intensity ratio of the NIR (<sup>4</sup>I<sub>9/2</sub> → <sup>4</sup>I<sub>15/2</sub>) to green (<sup>4</sup>S<sub>3/2</sub> → <sup>4</sup>I<sub>15/2</sub>) transitions, demonstrating exceptional performance for highly sensitive optical thermometry. This work not only provides a new strategy for designing thermally enhanced UCL materials but also underscores the great potential of layered perovskite oxyhalides as advanced platforms for optical temperature sensing.
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2025-11-10
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41201191
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Effective spot size parameters for Acuros dose calculation algorithm using enhanced leaf modelling: Estimation based on small rectangular MLC fields.
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Small field dosimetry plays a critical role in stereotactic radiotherapy, particularly for elongated fields shaped by multileaf collimators (MLCs). This study aims to optimize the Effective Spot Size (ESS) parameters in the Acuros dose calculation algorithm (Eclipse v18.0, with the enhanced leaf modelling ELM for MLC modelling) for accurate dose calculations of small, rectangular MLC-shaped fields. Measurements were based on the TRS-483 protocol and a recently proposed equivalent square field size determination method. Field output factors (FOFs) were measured using a Varian TrueBeam linear accelerator with HD-MLC for 6 MV and 10 MV beams (both flattened and unflattened). Symmetric square and rectangular fields (0.5-4 cm sides) were shaped by the MLC, with jaws fixed at 4.4 × 4.4 cm<sup>2</sup> to minimize scatter variation. Measurements were performed at isocenter, 10 cm depth using three detectors: microDiamond, PinPoint3D, and DiodeE. The microDiamond detector results were used for ESS optimization due to its complete output correction factor availability. FOFs were calculated in Eclipse v18.0 using Acuros with varying ESS values (0-1.5 mm). The optimal ESS was determined by minimizing FOF differences between calculated and measured values for extreme elongated field sizes in the studied range (0.5 × 4 cm<sup>2</sup> and 4 × 0.5 cm<sup>2</sup>). The optimized ESS parameters minimized FOF discrepancies between calculated and measured doses for elongated fields, improving calculation accuracy compared to vendor-recommended settings (ESSx = 0.5 mm, ESSy = 0.7 mm). Profiles and penumbra analyses supported these findings. ELM in Eclipse v.18 improves MLC modelling by representing rounded leaf ends. Only ESS parameters remain user-tunable. A method to determine the ESS for the Acuros algorithm is presented, resulting in accurate algorithm configuration for elongated small fields shaped by an HD-MLC. Results are presented using 6 MV and 10 MV beams, both flattened and unflattened for an HD-MLC Varian. ESS affects output factors and penumbra, with dose calculations matching measurements within 0.2% ± 0.4% and a maximum difference of 1.1%.
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2025-11-01
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41194690
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Effects of Three Different Ureteral Stents on Stent-Related Symptoms in Patients Undergoing Ureteroscopic Lithotripsy: Assessment Using the Ureteral Stent Symptoms Questionnaire.
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<b><i>Objective:</i></b> Ureteral stents are commonly used after ureteroscopic lithotripsy (URS) to prevent obstruction, but often cause stent-related symptoms (SRS), which can impact patients' quality of life. The Ureteral Stent Symptoms Questionnaire (USSQ) is a validated tool for assessing these symptoms. This study aimed to compare the SRS of three ureteral stents: conventional Double-J (cDJ, Tria), soft DJ (sDJ, Tria Soft), and loop-tail (LT, Polaris Loop), using the Japanese version of the USSQ. <b><i>Methods:</i></b> In this multicenter, prospective cohort study, 96 patients undergoing URS for upper urinary tract stones were enrolled and evenly assigned to one of the three stent groups. The USSQ was administered at baseline, 2 and 14 days after stent placement, and 2 weeks after stent removal. The primary end point was the USSQ score on postoperative day 14. The secondary end points included USSQ scores on day 2, postremoval, and score changes over time. Statistical analysis was performed using paired and unpaired <i>t</i>-tests, with <i>p</i> < 0.05 considered significant. <b><i>Results:</i></b> On day 14, the LT group showed significantly better general health index scores than the cDJ group (<i>p</i> < 0.001), whereas the sDJ group showed a favorable trend (<i>p</i> = 0.054). The LT group had worse scores in the sexual matters domain (<i>p</i> = 0.011), although all groups scored low. There were no significant between-group differences in urinary symptoms, pain, or work performance. The LT and sDJ groups had significantly better general health index scores than the cDJ group on day 2 and after removal. Urinary symptoms and pain were highest early poststenting and improved significantly over time (<i>p</i> < 0.001). <b><i>Conclusion:</i></b> The Polaris Loop stent significantly reduced SRS compared with the Tria stent, whereas the Tria Soft stent showed a favorable trend toward improvement. Because SRS is a major patient concern, general health should be considered alongside urinary and pain symptoms when selecting an optimal stent.
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2025-10-31
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41210115
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Protective effects of <i>Lactobacillus casei</i> and <i>Chlorella vulgaris</i> on cardiac gene expression (<i>NF-κB</i>, <i>Nrf-2</i>) and structural alterations in a <i>C57BL/6</i> mouse model of MASLD.
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most frequent chronic liver disease. The literature strongly links MASLD to increased epicardial fat thickness, left ventricular hypertrophy, and valvular calcifications. The effects of <i>Lactobacillus casei</i> and <i>Chlorella vulgaris</i> microalgae on MASLD prevention are good. NF-kB, Nrf-2, and cardiac tissue structural alterations in C57BL/6 mice produced MASLD were studied. Forty adult male C57BL/6 mice were allocated to five groups: control (CTL, standard chow), MASLD (high fat diet for 6 weeks), MASLD + <i>Chlorella vulgaris</i> (150 mg/kg), and MASLD + <i>Lactobacillus casei</i> (10<sup>8</sup> CFU/ml). Oral gavage needle-treated mice for 35 days. After blood drawing, dissection, and preparation, heart tissue stereology was assessed. Real-time RT PCR was used to analyze <i>NF-kB</i> and <i>Nrf-2</i> gene expression, and calorimetric methods were used to measure SOD, GPX, catalase, TAC, MDA, and LDH enzyme activity. <i>NF-kB</i> gene expression, ALT, LDH, AST enzyme activity, MDA concentration, left ventricle volume, cardiomyocyte volume, connective tissue volume, and capillary length increased significantly (<i>p</i> < 0.05). The treated groups showed significant decreases in <i>NF-kB</i> gene expression, ALT, LDH, AST, enzymes, MDA concentration, left ventricle volume, cardiomyocyte volume, connective tissue volume, capillary length, <i>Nrf-2</i> gene expression, and SOD, GPX, and TAC enzyme activity (<i>p</i> < 0.05). The present study showed that MASLD causes structural changes in the heart tissue to some extent. Also, administration of <i>Chlorella vulgaris</i> and <i>Lactobacillus casei</i> can reduce complications caused by MASLD.
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2025-12-01
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41185454
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Platelets During Myelin Repair in Multiple Sclerosis: Friend or Foe?
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Multiple sclerosis (MS) is an autoimmune neuroinflammatory demyelinating disease of the central nervous system (CNS) that affects more than 2.5 million people worldwide. Remyelination represents a robust regenerative response to myelin damage; however, during the later stages of MS, this process largely fails. Upon demyelination, oligodendrocyte progenitor cells (OPCs) proliferate, migrate, and differentiate into mature remyelinating oligodendrocytes. Why does remyelination fail in MS? Platelets are small, oval, anucleate cells that circulate in the bloodstream and form a hemostatic plug to stop blood leakage upon endothelial damage. Platelet function is not restricted to hemostasis; they also display tissue-regenerative activities. Here, we review evidence suggesting that platelets act as modulators of OPC function during remyelination. Additionally, we describe platelet alterations associated with MS that may contribute to remyelination failure. Finally, we highlighted our previous study that addressed these issues. This study showed that in response to myelin damage, platelets transiently accumulate within the lesion. Interestingly, platelet depletion leads to a reduction in OPC differentiation, hindering remyelination. In vitro studies revealed that transient exposure to platelets boosts OPC differentiation, whereas sustained exposure to platelets suppresses this beneficial effect. Consistent with this observation, in an in vivo model of thrombocytosis (Calr<sup>+/-</sup>), we found a sustained increase in the number of blood-borne platelets recruited into the CNS (as observed in MS lesions), resulting in a significant decline in OPC differentiation during remyelination. These findings reveal a complex role of platelets in remyelination and provide new insights for understanding the MS pathology as well as for designing regenerative strategies for the treatment of this disease.
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2025-11-01
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41208180
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Efficiency Recalibrates Social-Emotional Trade-Offs Behind Partner Choice in Direct Reciprocity through Intention-Specific Neural Bases.
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Direct reciprocity, in which beneficiaries return favors to benefactors, is a cornerstone of human cooperation. Previous empirical work addresses partner control-how individuals decide whether and how much to reciprocate-whereas the equally critical dimension of partner choice, deciding whom to reciprocate when aided by multiple benefactors, remains understudied. This gap is addressed by testing two determinants: social-emotional motivations and reciprocal efficiency (the efficiency of reinforcing future relational capital). Combining an interpersonal task with fMRI multivariate neural expressions and representational similarity analysis, it is demonstrated that efficiency recalibrates choices between altruistic and strategic benefactors by shifting the neural balance between distinct social-emotional concerns. When reciprocating to altruistic benefactors yielded higher efficiency, participants prioritized communal concerns (gratitude/guilt) represented in the ventromedial prefrontal cortex, whereas higher efficiency for strategic benefactors led them to prioritize obligation represented in the ventral striatum. General efficiency engaged the putamen, dorsomedial prefrontal, and orbitofrontal cortices; the inferior parietal lobe integrated efficiency-driven recalibration. These findings suggest that efficiency does not merely optimize material outcomes but adaptively reweights social-emotional concerns behind reciprocal partner choices, bridging economic models of rational choice with psychological theories of social emotions, offering insights into human cooperation and related practical applications.
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2025-11-09
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41176686
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Expansion of Variant Panels in Newborn Screening Algorithms to Identify Cystic Fibrosis: A Retrospective Analysis of 25 Years of Genotypes and Implications on Diagnosis.
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We seek to understand the incremental value of applying expanded variant panels or sequencing in population-based screening algorithms for a well-understood condition like cystic fibrosis (CF). We compared newborn screening methods to determine at what point do attempts to increase sensitivity of second-tier testing meet diminishing returns. Using the genotypes of all Massachusetts CF-affected patients who were born between February 1,1999 and January 31,2024, we retrospectively applied screening algorithms that used: (a) 39 CF gene (CFTR) variants, 139 CFTR variants, or CFTR sequencing, and (b) different algorithms for referral to CF Center. Sensitivity, specificity, and timing of diagnosis were evaluated. Our current 39 CFTR variant panel and referral algorithm yields a clinical sensitivity of 98.7%. In Massachusetts, expanding the variant panel might result in limited sensitivity improvement but if the referral algorithm requires detection of two CFTR variants, might decrease the sensitivity. Expanding the CFTR variants genotyped does not necessarily guarantee an increase in screening sensitivity. Using a conservative cutoff for DNA testing might accomplish as much. Screening turn-around time, costs, and geographic location of CF Centers should be factored into decisions about the benefit of NGS technology within newborn screening.
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2025-10-30
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41182795
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Categorizing tasks around a break reduces rumination and improves task performance.
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People often take short breaks from goal-related activities (e.g., at work, during exercise) to stay motivated and prevent burnout. The current research examines a novel factor influencing break effectiveness: task categorization. We suggest that the way people construe tasks around breaks influences their rumination about the task during the break, with consequences for postbreak performance. We test these predictions in a pilot study and five experiments. We find that when people frame a break as falling between two tasks rather than occurring in the middle of a single task, they are less likely to have negative ruminative thoughts about the task during the break (Experiments 1-3). We further examine a consequence of reducing this type of rumination: improved task performance. Using mediation (Experiment 4) and moderation (Experiment 5) approaches, we find that by reducing negative, ruminative thoughts, task categorization can improve postbreak task performance. Together, this research contributes to the literature on categorization, goal pursuit, performance, and breaks, with practical implications for reducing negative rumination. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
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2025-11-03
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41195892
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Gradient Hydrogel Electrolyte Enables High Ionic Conductivity and Robust Mechanical Properties for Dendrite-Free Aqueous Zinc-Ion Battery.
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Rechargeable aqueous Zinc-ion batteries (AZIBs) hold great promise for sustainable storage, yet their practical deployment is impeded by dendrite growth and hydrogen evolution reaction (HER). Hydrogel electrolytes offer a potential solution to stabilization but suffer from a trade-off in ionic conductivity and mechanical robustness. Herein, by leveraging the Hofmeister effect, the way ions influence the solubility, stability, and structure of polymers in aqueous solutions, a concentration gradient hydrogel electrolyte (CGHE) is designed to reconcile these challenges. By integrating two hydrogels with high (1.5 m OAc<sup>-</sup>) and low (0.3 m) acetate concentrations, the CGHE achieves a high Zn<sup>2</sup>⁺ transference number ( <math xmlns="http://www.w3.org/1998/Math/MathML"> <semantics><msub><mi>t</mi> <mrow><mi>Z</mi> <msup><mi>n</mi> <mrow><mn>2</mn> <mo>+</mo></mrow> </msup> </mrow> </msub> <annotation>${t_{Z{n^{2 + }}}}$</annotation></semantics> </math> = 0.88) and excellent mechanical strength (σ = 1.7 MPa, ɛ<sub>max</sub> = 310%). The quasi-solid gradient architecture regulates Zn<sup>2+</sup> transport and cation selectivity, promoting uniform Zn (002) deposition while suppressing HER through reduced water activity in the networks. Consequently, symmetric Zn//Zn cells exhibit ultrastable cycling over 2,500 h at 1 mA cm<sup>-2</sup>, and Zn//Cu asymmetric cells deliver a coulombic efficiency of 99.1%. The Zn//hydrogel//V<sub>2</sub>O<sub>5</sub> full batteries retain 91% of capacity after 500 cycles at 2 A g<sup>-1</sup>, while the quasi-solid electrolyte offers flexibility and flame resistance, enabling potential safe operation in wearable devices. The gradient electrolyte design provides a general strategy for constructing advanced electrolytes in metal-based energy systems.
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2025-11-06
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41200297
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Protective effect of capsaicin on AKT1 and MAPK1 expression in the liver of mice (<i>Mus musculus</i>) induced by aflatoxin B1.
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The metabolism of toxins after ingestion by animals involves transformation into various metabolites with different levels of toxicity. Aflatoxin B1 undergoes biotransformation into various compounds in the mitochondria that are closely related to its toxic effects. <i>Capsicum annuum</i> L. or chili is a plant that produces a spicy taste and sharp aroma produced by capsaicinoid compounds. Capsaicin <i>in vitro</i> has been shown to have effects on various cell types, including prostate cells, cells that undergo proliferation in the stomach, and hepatocytes, without causing significant side effects on normal cells. This study aimed to determine whether capsaicin inhibits the expression of alpha serine/threonine-protein kinase 1(AKT1) and mitogen-activated protein kinase 1 (MAPK1) target proteins <i>in vivo</i> by scoring using immunohistochemistry (IHC) and histopathological hepatic staining hematoxylin-eosin (HE). IHC was performed by counting the number of transformed cells using monoclonal antibodies and liver pathogenicity was assessed by scoring hepatic lesions (congestion, degeneration, and necrosis) using HE staining preparations. Capsaicin treatment significantly reduced liver damage and aflatoxin B1-induced protein expression. Histopathological scores for degeneration, congestion, and necrosis were significantly lower in the aflatoxin B1 (AFB1) + capsaicin group (P3: 15.42 ± 0.65, 15.50 ± 0.50, 15.50 ± 0.58) than in the AFB1-only group (P2: 21.50 ± 0.57 for all variables; <i>p</i> < 0.05). Immunohistochemical analysis showed that capsaicin co-treatment decreased AKT1 (P3: 16.33 ± 0.69 vs. P2: 19.75 ± 0.56) and MAPK1 expression (P3: 13.83 ± 0.61 vs. P2: 20.00 ± 0.34), with a statistically significant reduction in MAPK1 expression (<i>p</i> < 0.05). Capsaicin demonstrated a protective effect by reducing liver damage and downregulating AKT1 and MAPK1 expression in mice with aflatoxin B1-induced hepatotoxicity.
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2025-09-01
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41181140
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Retraction: Mast cells in skin scarring: a review of animal and human research.
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[This retracts the article DOI: 10.3389/fimmu.2020.552205.].
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2025-01-01
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41168049
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Remnant cholesterol and associations with incidence, progression, and change in coronary artery calcium in South Asian Americans.
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Remnant cholesterol (RC) may contribute to residual risk of atherosclerotic cardiovascular disease (ASCVD), but few studies have examined this in South Asian populations, who experience a disproportionately high incidence of ASCVD. Using data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study, a community-based longitudinal cohort of South Asian men and women without ASCVD at baseline, we examined the association between RC and change in coronary artery calcium (CAC). Baseline fasting blood specimens and questionnaires were obtained between 2010-2013. CAC was assessed both at baseline and after 5-year follow-up in 698 participants. We used multivariable linear and logistic regression to examine relationships between RC quartile and CAC incidence (no CAC at baseline to any CAC at examination 2), CAC progression, and overall change in CAC. In 892 MASALA study participants at baseline, mean RC was 25.8 ± 11.8 mg/dL. Incident CAC occurred in 25.8% of participants and increased across RC quartiles (P = .002). After covariate adjustment, individuals with RC levels in the third (odds ratio [OR]: 2.24, 95% CI: 1.01-4.98) and fourth quartiles (OR: 2.57, 95% CI: 1.20-5.51) had significantly higher odds of incident CAC after 5 years than those in the lowest RC quartile. These associations persisted after sequential adjustment for behaviors, adiposity, and measures of insulin sensitivity and did not vary by gender. RC quartiles were not associated with CAC progression or CAC change. Higher RC levels were associated with increased odds of incident CAC independent of risk factors for ASCVD.
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2025-10-28
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41172645
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Production, crystallographic studies, and functional profiling of γ-carbonic anhydrase from the probiotic Limosilactobacillus reuteri: In vitro and cell-based insights.
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Limosilactobacillus reuteri (formerly Lactobacillus reuteri) is a probiotic bacterium involved in maintaining gut microbiota balance and modulating immune response. In this study, for the first time, we report the recombinant production and kinetic characterization of its γ-class carbonic anhydrase (CA, EC 4.2.1.1), referred to as LreCAγ. The enzyme catalyzes CO<sub>2</sub> hydration with an efficiency comparable to that of other bacterial γ-CAs, although lower than that of α-hCA II. X-ray crystallization studies shed light on the enzyme structure, and inhibition studies with anions, sulfonamides, and related compounds revealed that LreCAγ is less susceptible to inhibition compared to the γ-class CA from Vibrio cholerae, used for comparison. Otherwise, activation assays with selected amines and amino acids identified the two enantiomers of His (25 and 26) as the most potent LreCAγ activators. Stereochemistry had a minimal impact on activity, except for L-Phe (27), which was twice as potent as its d-enantiomer (28). To assess the biological effects of CA modulation, E. coli DH5α, which expresses several CAs, was used as a model organism. CA activators were tested alone and in combination with the pan-CA inhibitor acetazolamide (AAZ), revealing CA-dependent effects on bacterial growth. Additionally, selected CA activators were evaluated for their effects on human macrophages and intestinal epithelial cells, with L-Trp (31) attenuating LPS-induced activation and exhibiting good biocompatibility in normal intestinal cells. Taken together, these results underscore the feasibility of targeting LreCAγ activation as a strategy to enhance probiotic efficacy.
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2025-10-25
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41189685
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Therapeutic potential of natural polymer-based transdermal drug delivery system for musculoskeletal disorders.
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The transdermal drug delivery system is a highly safe and well-tolerated therapeutic approach with significant potential for treating musculoskeletal disorders. However, its clinical application is limited by the low skin permeability of many active drugs in its formulations. To overcome this challenge, advancements in skin permeation enhancement techniques are essential. Over the past decade, natural polymers have been increasingly incorporated into various nanocarriers due to their availability, biodegradability, and biocompatibility, offering new options for the effective dispersion of suspended solids. Furthermore, surface functionalisation of the numerous functional groups found in natural polymers allows them to be transformed into targeted and stimulus-responsive materials, enabling precise drug delivery to musculoskeletal tissues. This review examines the mechanisms of action of natural polymer-based transdermal drug delivery system, covering penetration enhancers, nanoparticles, microneedles, hydrogels, and nanofibres derived from chitosan, hyaluronic acid, sodium alginate, cellulose, and proteins, and their applications in treating musculoskeletal disorders. Moreover, it outlines the current challenges and prospects of polymer-based transdermal drug delivery system for localised treatment, offering insights into current therapeutic approaches and proposing new directions for advancements in this field.
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2025-01-01
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41183181
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Randomized Controlled Trial of Mechanical Thrombectomy With Anticoagulation Versus Anticoagulation Alone for Acute Intermediate-High Risk Pulmonary Embolism: Primary Outcomes from the STORM-PE Trial.
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Patients with intermediate-high risk pulmonary embolism (PE) have an elevated right-to-left-ventricular (RV/LV) diameter ratio and are at risk of early clinical decompensation and mortality. Reperfusion therapy aims to rapidly relieve acute RV pressure overload and normalize hemodynamics. STORM-PE is the first reported randomized controlled trial (RCT) to test the efficacy and evaluate the safety of mechanical thrombectomy (MT), specifically computer assisted vacuum thrombectomy (CAVT) with anticoagulation (AC) compared to AC alone. STORM-PE is an international RCT with 1:1 randomization to CAVT with AC or AC alone. Eligible adults had acute onset (symptoms ≤14 days), intermediate-high risk PE, and were normotensive, with an RV≤LV ratio ≥1.0 on computed tomography pulmonary angiography and elevated cardiac biomarkers. The primary endpoint analysis tested for a difference between groups for the change in RV/LV ratio at 48 hours, assessed by a blinded independent imaging core laboratory. Secondary endpoints included major adverse events (MAE) within 7 days (a composite of clinical deterioration necessitating rescue therapy, PE-related mortality, symptomatic recurrent PE, and major bleeding), adjudicated by an external clinical events committee. Additional outcomes included change in vital signs and core lab assessed PA obstruction at 48 hours. A total of 100 patients enrolled across 22 sites were randomized to CAVT (N=47) or AC alone (N=53). Baseline characteristics were comparable between arms. At 48 hours, mean reduction in RV/LV ratio was greater for CAVT (0.52±0.37) than AC (0.24±0.40), a difference of 0.27 (95% CI, 0.12, 0.43; <i>P</i><0.001). Refined modified and modified Miller score exhibited greater changes for CAVT than AC at 48 hours (<i>P</i><0.001). Early normalization of vital signs within 48 hours was more frequent after CAVT. The MAE rate within 7 days was not different between groups (CAVT 4.3% vs AC 7.5%, <i>P</i>=0.681). Two PE-related deaths occurred in the CAVT arm. CAVT was superior to AC alone in reducing RV/LV ratio within 48 hours in intermediate-high risk PE patients, accompanied by earlier normalization of vital signs and comparable MAE rates to AC.
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2025-11-03
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41181722
|
Safety of Sodium Zirconium Cyclosilicate in Critically Ill Patients With Impaired Gastric Motility: A Case of Persistent Intragastric Precipitation.
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Sodium zirconium cyclosilicate (SZC) is a novel potassium-binding agent used to treat hyperkalemia. Although SZC is generally considered safe, its efficacy and safety in critically ill patients remain unclear. We report a novel adverse event of persistent intragastric SZC precipitation in a critically ill patient. A man in his 20s was admitted after a cardiac arrest and developed hyperkalemia and renal dysfunction. Following four days of SZC administration via a nasogastric tube, chest radiography revealed a high-density intragastric mass. Gastric lavage and Gastrografin administration confirmed the presence of the precipitate and revealed severely impaired gastric motility. This case highlights the potential risks of SZC use in critically ill patients with impaired gastric motility. Factors contributing to precipitation include decreased bowel peristalsis due to intestinal ischemia and the use of sedatives and vasopressors. Close radiographic monitoring of SZC transit is recommended for early detection. Further research is required to establish optimal management strategies for such adverse events.
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2025-10-01
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41172768
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Influence of resin structure on the prediction of two-component protein adsorption behavior in anion exchange resins from single component batch data.
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Understanding the adsorption equilibria and kinetics of multicomponent mixtures is essential to developing and modeling separation processes. In our previous research, we demonstrated the significant impact of resin structure on the efficiency with which two components are separated in frontal chromatography. This study aims to predict the adsorption behavior of multicomponent binary protein mixtures using single-component data on anion exchange resins. Conalbumin (CA) and green fluorescent protein (GFP) were used as model proteins to study two resins with distinct structures: Q Sepharose FF and POROS 50 HQ. Q Sepharose FF has a homogeneous pore size distribution (r<sub>pore</sub> ∼ 30 nm), while POROS exhibits a bimodal distribution with macropores (r<sub>pore</sub> ∼ 200-500 nm) and micropores (r<sub>pore</sub> ∼ 20 nm). A pore diffusion model with a competitive Langmuir isotherm was used to predict binary adsorption behavior using single-component isotherm and batch uptake kinetics data. While this model accurately described adsorption on Q Sepharose FF, it failed to capture the reduced GFP binding capacity observed in frontal chromatography on POROS 50 HQ by a factor of 2. To address this, two alternative models were proposed: (1) a competitive bi-Langmuir isotherm assuming heterogeneous binding sites and (2) a reversible-irreversible binding model where micropore sites exhibit irreversible adsorption. The reversible-irreversible model provided the most accurate predictions for POROS 50 HQ, capturing both equilibrium and kinetic data with an average deviation below 15 %. These findings highlight the role of POROS's bimodal pore structure in reduced GFP capacity and demonstrate the need for advanced mechanistic models to predict multicomponent adsorption in complex systems.
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2025-10-24
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41177558
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Neonatal glucose-6-phosphate dehydrogenase activity by gestational age and sex: evidence-based cut-offs for newborn screening in Saudi Arabia.
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To characterise quantitative glucose-6-phosphate dehydrogenase (G6PD) activity in term and preterm neonates, compare activity by gestational age (GA) and sex and derive neonatal screening cut-offs using percentile and WHO methods. Retrospective cross-sectional analysis of cord blood screening programme. King Abdulaziz Medical City, Riyadh, Saudi Arabia, January 2016 to May 2022. All live births with cord blood G6PD and GA. Of 59 465 births, 58 139 (97.8%) were screened. For reference range derivation only, results below the adult threshold (<5.7 U/g haemoglobin (Hb); n=1163) were excluded, yielding 56 976. Distribution by GA and sex; prevalence under three definitions: adult cut-off (≤5.7 U/g Hb), neonatal percentile cut-off (2.5th percentile) and WHO bands (<30% deficient, 30-70% intermediate, >70% normal). Secondary measures were stratum medians and the male share among detected cases. Mean activity was 15.33±2.67 U/g Hb, higher in preterm than term. Sex differences were absent in preterm strata but present at term (males lower than females; p=0.002). The neonatal 2.5th percentile cut-off was 9.9 U/g Hb. Using the adult cut-off, 2.00% (1163/58 139) were deficient, 80.9% male. Using the neonatal cut-off, prevalence rose to 4.97% (2888/58 139), adding 1725 infants (+583 males, +1142 females) and reducing the male share to 52.8%. WHO bands identified a small <30% group and a female intermediate (30-70%) group across strata. Medians were 15.0 (≥37 weeks), 16.0 (33-36), 17.0 (29-32) and 17.6 (≤28) U/g Hb. G6PD activity in neonates shows clear GA and sex effects. Adult cut-offs underestimate deficiency, especially in females. Neonatal thresholds (2.5th percentile plus GA-specific WHO bands) improve detection. Adoption within newborn screening, with reporting of a female intermediate band, should strengthen follow-up; external validation and linkage to bilirubin outcomes are needed.
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2025-11-02
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41162403
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Microbiome and well-being: a meta-analysis.
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The human microbiome may play a significant role in both health and disease. However, most studies to date have focused on the microbiome's role in pathogenesis, while its potential role in promoting well-being remains underexplored. We conducted the first meta-analysis synthesizing empirical evidence on associations between the human microbiome and psychological well-being. Based on eight analyzed studies (N = 2526 participants), we found that both microbial diversity and taxonomic abundance were positively associated with psychological well-being, with diversity emerging as the stronger predictor. Notably, these associations appeared consistent across sex and age. This study provides preliminary evidence that microbiome composition may support salutogenic processes and offers a foundation for future integration of microbiome science into psychological and clinical interventions. However, given the small number of empirical studies included in the meta-analysis, the generalizability of these findings remains limited. Further research is required to strengthen and refine our understanding of the microbiome-well-being relationship.
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2025-10-29
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41172118
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Families' and therapists' experience of a telehealth programme for children and adolescents with cerebral palsy during the COVID-19 pandemic.
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To understand how families and therapists perceived their participation in an individualized home telehealth programme implemented for children and adolescents with cerebral palsy (CP) during the COVID-19 pandemic in Brazil. This was a descriptive qualitative study that included 13 families of children and adolescents with CP (classified in Gross Motor Function Classification System levels IV and V) and 20 therapists, who participated in an individualized home telehealth programme. Semi-structured, online interviews were carried out with participants after completing the intervention to understand their expectations, challenges, and benefits, and to gather suggestions for future services. The interviews were transcribed for thematic analysis. The three themes were (1) fear of the unknown, (2) new pathways, and (3) benefits and future perspectives. Participants recognized that active family engagement during the intervention, the establishment of individualized goals, and communication between parents and therapists led to changes in children's involvement, family routines, and parental empowerment regarding their children's rehabilitation process. The establishment of a partnership between therapists and families, by combining technical knowledge and living experience, contributed to the successful implementation of the intervention. Future actions may involve the adoption of hybrid intervention models focused on the specific needs of families of children and adolescents with CP.
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2025-10-31
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41184865
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Risk stratification and healthcare disparities in COVID-19 outcomes: a retrospective cohort study of treatment pathways before and after infection.
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COVID-19 infections continue globally post-pandemic. Analyzing treatment pathways and clinical outcomes remains essential for understanding prognostic factors. We reviewed medical records of COVID-19-positive outpatients and inpatients from Wenling Hospital of Traditional Chinese Medicine (January 2022-April 2024). Logistic regression (Python) evaluated hospitalization predictors. Paired t-tests (SPSS) and ICD-11-coded disease comparisons assessed pre/post-infection changes. Among 664 patients, outpatients (mean age 41.99) were younger than inpatients (mean age 74.48), with more females in outpatient care (57.69% vs. 43.45% inpatient). Patients aged 71-85 years comprised over 50% of hospitalizations. Women showed more mild cases while men had more severe infections. Logistic analysis associated hospitalization with age and urban residency, not gender. Rural residents had higher hospitalization rates than urban populations. Hospitalization odds increased with patient age (0-80 years). Outpatients demonstrated increased digestive system disorders post-infection, while inpatients showed 13.42% more total diseases, particularly neurological disorders. Outpatient disease outcomes remained stable pre/post-infection (P = 0.924), whereas inpatients showed significant changes (P = 0.031). Hospitalization correlated with age and urban/rural status, peaking in 71-85-year-olds (predominantly male). Rural residents faced higher hospitalization risk. Age showed linear relationship with hospitalization likelihood (50-70 years). Post-infection neurological disorders in inpatients and digestive issues in outpatients require clinical attention. More females sought outpatient care, though gender didn't predict hospitalization.
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2025-11-03
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41172526
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Population ecology of bivalve mollusks in beach sediments on the southern coast of Espírito Santo, Brazil.
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This study examined the population ecology of bivalve mollusks on Central Beach in Piúma, southern Espírito Santo, Brazil, over one year (August 2018 to July 2019). Sampling was conducted along four transects perpendicular to the shoreline, with sediment characteristics and benthic community structure analyses. 2,104 individuals were identified, representing 5 orders, 8 families and 13 species. The most abundant species were Anomalocardia flexuosa (39.78%), Strigilla carnaria (28.90%), Donax gemmula (11.93%), and Tivela mactroides (11.07%). The consistent presence of juveniles and recruits indicated that the area serves as a natural nursery for these species. Transect A, closest to the mouth of the Novo River, showed the highest organic matter content in the sediment and the most significant dominance of A. flexuosa, which was positively correlated with organic matter levels (p< 0.0001). Conversely, alpha diversity was negatively correlated with organic matter content (p= 0.0497). Sediment granulometry was uniform across transects, mainly of moderately sorted fine sand. Rainfall did not significantly affect ecological indices or the abundance of dominant species, suggesting that the bivalve community is resilient to seasonal climatic variations. These results highlight the environmental significance of Central Beach in Piúma as a vital estuarine habitat, particularly for A. flexuosa, and emphasize the need for integrated coastal management strategies that account for both marine and continental influences.
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2025-01-01
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41191615
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Brain volumetric reductions in patients with thrombotic thrombocytopenic purpura.
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Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder caused by a deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). The recognition of increased morbidity and mortality in patients after recovery suggests that TTP may become a chronic disease with possible multiple adverse outcomes throughout life. Neurological disorders may occur in the acute phase of TTP due to several pathophysiological mechanisms. These mechanisms include the formation of microvascular thrombosis in capillaries or small arteries of the central nervous system (CNS), leading to transient or permanent ischemic brain damage. However, the causes underlying chronic neurological involvement in TTP are not fully understood, particularly in long-term survivors. Therefore, the aim of this study is to evaluate brain volumetry in TTP patients in remission and to correlate it with the neurological involvement associated with the disease. The study cohort includes 16 consecutive patients diagnosed with TTP between 1995 and 2016 at the Hospital de Clinicas, Universidade Estadual de Campinas (HC-UNICAMP), in Brazil. We performed MRI of the patients' skull. Brain volume and parts of the central nervous system were analyzed and segmented using FreeSurfer. The CNS volumetry of 16 TTP survivors was analyzed and compared with that of 20 age- and sex-matched controls. TTP survivors showed a reduction in intracranial volume (1,019 cubic liters (L3)) compared to the control group (1,280 L3), with a P value of 0.0003. The nucleus accumbens showed a significant reduction on the left side (469 mm3 in TTP survivors X 605 mm3 in controls, P = 0.02). The cerebellar cortex showed a reduction on the right side (44176.50 mm3 in TTP survivors X 47283.15 mm3 in control group, P = 0.05) and on the left side. Our study demonstrated a significant reduction in brain and nucleus accumbens volume in patients with TTP compared with a healthy control group. These findings suggest a possible lasting impact of TTP on the CNS and highlight the importance of continued monitoring and intervention to reduce neurological complications in patients after the acute phase of the disease. Future studies are needed to validate our results and elucidate the mechanisms underlying the brain changes observed in patients with TTP. Our findings provide valuable information for developing more effective treatment strategies and improving the quality of life of patients with TTP.
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2025-01-01
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41171134
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gcMeta 2025: a global repository of metagenome-assembled genomes enabling cross-ecosystem microbial discovery and function research.
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The rapid growth of metagenomic sequencing has generated an unprecedented wealth of metagenome-assembled genomes (MAGs), transforming opportunities for microbial discovery and functional characterization. Yet, full utilization of these resources has been constrained by heterogeneous data generation practices and inconsistent analytical pipelines. The gcMeta database addresses this gap by compiling MAGs through both public acquisition and de novo assembly. This release integrates over 2.7 million MAGs from 104 266 samples spanning various biomes, covering human, animal, plant, marine, freshwater, and extreme environments. It establishes 50 biome-specific MAG catalogues comprising 109 586 species-level clusters, of which 63% (69 248) represents previously uncharacterized taxa, and annotates >74.9 million novel genes. By linking functional traits with microbial co-occurrence networks, gcMeta identifies keystone taxa central to biogeochemical cycling and environmental adaptation. The platform further supports cross-ecosystem functional comparisons, revealing niche-specific metabolic pathways and stress-response genes. Moreover, gcMeta provides standardized, AI-ready datasets encompassing microbial enzymes, anti-phage defense systems, and other functional modules, enabling advanced machine learning applications. By bridging microbial "sequence discovery" with "functional utilization," gcMeta establishes a foundation for ecological research, industrial biotechnology, and novel gene mining. The platform is freely accessible at https://gcmeta.wdcm.org/.
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2025-10-31
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41189699
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Overview of approved COVID-19 vaccines in the EU, recommendations for use in Sweden and vaccine uptake over time: Report from the Swedish Medical Products Agency and the Public Health Agency of Sweden.
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The aim of this review is to describe the regulatory background of the COVID-19 vaccines, the national recommendations for use issued and vaccine uptake in Sweden. It includes an overview of licensing and relevant safety aspects identified by the European Medicines Agency (EMA) and the national vaccination plan issued by the Public Health Agency (PHA) of Sweden. Information on dates of licensing and safety aspects of importance identified by EMA published on its website, was compiled and presented in a chronological order. National recommendations on COVID-19-vaccination and vaccinations-data on uptake and coverage using the national-vaccine-register are presented. COVID-19 vaccines development, assessments using rolling review and licensing of the covid-19 vaccines was done in 2020 during less than a year. Large-scale production was implemented. Monthly safety reviews performed by the EMA identified risk for thrombosis with thrombocytopenia syndrome with adenoviral vaccines and myocarditis for mRNA vaccines which led to restrictions in national recommendations for specified groups.National vaccinations were launched in a phased manner during 2021. Persons of high age, risk groups and nursing home personnel were prioritised during primary vaccinations and for initial boosters. In the Swedish population, 85% recieved at least on vaccine dose from the age of 12. At least two doses were recieved by 81% from age 18 and 95% from age 80. Recommendations for national use adhered to relevant adverse drug reactions identified. The vaccine coverage was high. Timelines presented should be considered in follow-up studies of COVID-19-vaccines to manage possible selection bias and confounding.
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2025-01-01
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41197483
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Estimating the causal impact of the Paris agreement on the ESG market: A Bayesian structural time-series approach.
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This study uses a Bayesian structural time-series model to examine the causal impact of the Paris Agreement on Environmental, Social, and Governance (ESG) markets across 18 countries. The research addresses key gaps in understanding the long-term effects of international climate agreements on sustainable finance. By analyzing MSCI ESG Leaders indices from 2013 to 2022, the study reveals significant variations in the agreement's impact across different economies. Countries like China and Indonesia experienced substantial increases in their ESG indices (31.01 %), while others like the UK saw decreases (-2.63 %). A structural break analysis serves as a robustness test, confirming significant shifts in ESG indices coinciding with the Paris Agreement's adoption in 2015. The study also highlights subsequent structural breaks in 2017, 2019, and 2021, reflecting ongoing regulatory changes and global events affecting ESG markets. This research contributes to a more nuanced understanding of how international climate policies shape sustainable investment practices, offering valuable insights for policymakers and investors navigating the evolving landscape of climate finance.
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2025-11-05
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41185814
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Adiponectin Paradox in Coronary Artery Bypass Graft Patients: A Comparative Analysis of Pericardial Fluid and Plasma Levels.
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Background Adiponectin is an anti-inflammatory and cardioprotective adipokine involved in the regulation of glucose and lipid metabolism. Although it has been extensively studied in blood, data on its concentrations in pericardial fluid remain scarce. Objectives This study aimed to assess adiponectin levels in plasma and pericardial fluid of patients undergoing coronary artery bypass grafting (CABG) and to evaluate their clinical significance in comparison with healthy individuals. Methodology Pericardial fluid and plasma samples were obtained from 50 patients who underwent CABG, while plasma samples were collected from 50 healthy controls. Adiponectin levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. Results In the patient group, the plasma adiponectin level was 7.68±1.76 ng/mL (median: 7.70), while the pericardial fluid level was 8.70±3.16 ng/mL (median: 8.56). The plasma level in the healthy control group was 5.25±0.77 ng/mL (median: 5.20), significantly lower than that in the patient group (p<0.001). No significant difference was observed between patient plasma and pericardial fluid levels (p=0.070). The receiver operating characteristic (ROC) analysis revealed a high discriminative power of plasma adiponectin levels in distinguishing patients from controls, with an area under the curve (AUC) value of 0.901. Conclusion Elevated adiponectin levels in both plasma and pericardial fluid of CABG patients suggest regulation by systemic and local mechanisms, possibly via epicardial adipose tissue. This pattern aligns with the "adiponectin paradox," where increased levels may reflect a compensatory response or cardiac stress in advanced disease. Pericardial fluid assessment provides novel insights into the cardiac microenvironment with potential diagnostic and prognostic value.
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2025-10-01
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41202890
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Prevalence and clinical impact of baseline atherosclerotic vascular disease in patients undergoing transcatheter aortic valve implantation: A meta-analysis.
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Degenerative aortic valve disease and atherosclerotic vascular disease (ASCVD) frequently coexist. ASCVD may impact pre-procedural planning and patient outcomes. To systematically quantify the prevalence and prognostic significance of prior coronary artery disease (CAD), peripheral artery disease (PAD), and cerebrovascular event (CVE) in patients undergoing transcatheter aortic valve implantation (TAVI). A systematic literature search was conducted to identify studies reporting the prevalence of baseline ASCVD in patients undergoing TAVI. Meta-analyses were conducted to synthesize 1) the prevalence of pre-existing CAD, PAD and CVE in patients undergoing TAVI and 2) the prognostic effects of these comorbidities for post-TAVI mortality. A total of 43 studies (14 randomized) fulfilled the inclusion criteria encompassing a total of 732,895 patients undergoing TAVI (51 % males, pooled mean age of 81.2 years and Society of Thoracic Surgeons' score of 5.3). Of these, 48 % (42-55 %) had pre-existing CAD, 16 % (13-20 %) had PAD, and 11 % (9-12 %) had suffered a prior CVE. The baseline presence of CAD, PAD and CVE was independently linked with worse prognosis. Significant heterogeneity was observed among included studies, partially explained by differences in sample size, geographical location, and baseline patient characteristics. This aggregate meta-analysis of large-scale studies yielded a high prevalence of ASCVD in patients undergoing TAVI. Every second patient had CAD, every sixth patient had PAD and 1 out of 10 had CVE. The presence of each comorbidity increased independently the risk of long-term mortality. These findings can help navigate pre-procedural planning, resource allocation, and ultimately optimize overall TAVI outcomes.
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2025-11-05
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41182510
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Restoring failed inhibition in the substantia nigra pars reticulata suppresses absence seizures in rats.
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For over four decades, the substantia nigra pars reticulata (SNr) has been recognized as a critical structure in the modulation of seizure activity. Pharmacological and optogenetic inhibition of the SNr produces robust seizure suppression in a range of seizure models. These findings have given rise to a longstanding, yet unresolved question: do seizures involve a failure of inhibition within the SNr? We recorded single-unit activity in the SNr during spike-and-wave discharges (SWDs) in male and female WAG/Rij rats, a model of genetic absence epilepsy. We monitored extracellular γ-aminobutyric acid (GABA) levels using intensity-based GABA sensing fluorescence reporter (iGABASnFR). To emphasize the multi-modal efficacy of SNr inhibition on seizure suppression, we optogenetically inhibited the SNr. Fifty percent of recorded neurons exhibited a marked increase in firing at SWD onset, with activity returning to baseline at SWD termination. Extracellular GABA levels revealed a decrease in fluorescence during SWDs, consistent with reduced GABAergic transmission. Optogenetic inhibition of SNr neurons using continuous (open-loop) inhibition, but not closed-loop (responsive) inhibition, significantly reduced SWD incidence. These data suggest that a loss of GABAergic input to the SNr is associated with increased neuronal activity. Optogenetically restoring inhibition effectively reduced seizure burden. Together, these findings address a long-standing gap in the literature and provide compelling evidence that impaired inhibition within the SNr contributes to seizure expression.
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2025-11-03
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41198283
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Validation of the use of ToF-SIMS for analysis of glycosaminoglycans.
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Glycosaminoglycans (GAGs) have a range of biological roles and are of particular interest for their pharmaceutical efficacy and their potential as biomarkers or drug targets. Heparin, used globally as an anticoagulant and an antithrombotic, is predominantly derived from porcine sources but bovine and ovine sources are increasingly being considered to reduce the substantial risk of reliance on a single animal species. However, high sensitivity chemical discrimination of heparins from different species is a significant analytical challenge. In this study ToF-SIMS analysis of GAGs is investigated as a methodology to achieve specific chemical discrimination between GAGs of different types and heparins from different animal sources. The ToF-SIMS data acquisition is relatively fast (≈1 min per sample) and requires minimal sample amounts (75 pg of sample analysed). Multivariate analysis (MVA) models enabled high selectivity between GAG type and animal source of heparin, and for the high sensitivity detection of GAG-contaminants within porcine derived heparin. Contaminants are detected down to 0.001 wt%, with the exception of ovine derived heparin where differences could be detected to 0.01 wt%. Assessments of specificity, precision, robustness and quantification limits are conducted to validate the approach for heparin analysis.
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2026-01-01
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41211846
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Regulating the Li/Ni Mixing Ratio to Enhance Transition Metal-Lattice Oxygen Interaction for Achieving Long Life Lithium-Rich Layered Oxides.
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Lithium-rich layered oxides (LLOs) emerge as promising cathode materials for next-generation high-performance Li-ion batteries (LIBs) due to their superior specific capacity characteristics. The similar ionic radii of Li<sup>+</sup> (0.72 Å) and Ni<sup>2+</sup> (0.69 Å) inevitably cause Li/Ni mixing. However, the relationship between Li/Ni mixing and the electrochemical performance of LLOs remains poorly understood. This study investigates LLOs with varying Li/Ni mixing ratios. The results indicate that an optimal increase in Li/Ni mixing can strengthen TM─O bond, reduce lattice strain, and thus enhance the cycling stability of LLOs. When the Li/Ni mixing further increases, Ni atoms tend to aggregate in the Li layer, which reduces the structural stability of LLOs and causes severe electrolyte decomposition. In comparison to the sample with lower Li/Ni mixing (1.90%), the LLOs with optimized Li/Ni mixing (4.07%) exhibit an enhancement in initial Coulombic efficiency from 83.0% to 87.4%, along with an improvement in capacity retention from 71.7% to 85.2% after 500 cycles at 1C. Moreover, the corresponding pouch cell maintains 82.5% capacity retention after 200 cycles at 0.3C. This study elucidates the impact of Li/Ni mixing ratio on the electrochemical performance of LLOs, providing valuable insights for synthesizing high-performance LLOs.
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2025-11-10
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41179853
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A One-Year Retrospective Observational Study of an Occupational Medicine Outpatient Clinic in a City Hospital.
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<i>Background:</i> Occupational diseases (ODs) remain a major public health concern. Despite advances in occupational health (OH), many workers remain at risk due to insufficient preventive measures and limited access to specialized care. <i>Objective:</i> This study aimed to evaluate the sociodemographic and occupational characteristics of patients attending an ODs outpatient clinic in Türkiye and to assess associated risk factors. <i>Methods:</i> We retrospectively analyzed data from 326 patients in a descriptive observational study. Variables included age, sex, work duration, income, education, personal protective equipment (PPE) use, and diagnosis. <i>Findings:</i> The mean age was 48.1 years, and 89.3% of participants were male. ODs were diagnosed in 42.3% of patients, with pneumoconiosis being the most common (34.1%). Longer employment duration significantly increased risk (OR: 1.06; 95% CI: 1.03-1.09; <i>p</i> < 0.001). Income was also significant: both below- (OR: 2.79; 95% CI: 1.20-6.49; <i>p</i> = 0.017) and above-minimum-wage earners (OR: 2.52; 95% CI: 1.00-6.37; <i>p</i> = 0.050) had a higher risk. Most participants reported dust (79.4%) and ergonomic exposures (77.6%). Consistent mask use was 12.0% and hearing protection 7.7%. PPE use was insufficient in smaller workplaces but relatively higher in larger ones. Women began working later than men (26.2 vs. 17.3 years; <i>p</i> < 0.001). Most participants (85.9%) had social security coverage, yet 16% worked after retirement. <i>Discussion:</i> Improving OH practices, particularly in small enterprises where PPE use is inadequate, expanding worker training and workplace inspections, and ensuring access to OH services for self-employed individuals are critical for effective prevention of ODs. Additionally, addressing socioeconomic factors such as income disparities may further reduce occupational disease risk.
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2025-01-01
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41191684
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A 5-Year Survey on Multiple Targeted Benzimidazole Hybrids.
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Among heterocyclic compounds, the various biological activities and the easily modifiable chemical structure of benzimidazole compounds make them important in drug development. Currently, the demand for treatments targeting multiple biological pathways is increasing. In the treatment of multifaceted diseases, drugs exhibiting multiple therapeutic effects and low toxicity are particularly advantageous. In this context, the ability of benzimidazole compounds to form hybrid structures that target multiple biological mechanisms is noteworthy. In this review, studies on the multifaceted biological activities of hybrid benzimidazole derivatives-including benzimidazole-triazole, benzimidazole-thiazole, benzimidazole-oxadiazole, benzimidazole-quinoline, benzimidazole-hydrazone, benzimidazole-benzimidazole, benzimidazole-thiadiazole, benzimidazole-piperazine, benzimidazole-imidazole, benzimidazole-benzothiazole, benzimidazole-coumarin, benzimidazole-indole, benzimidazole-Schiff base and benzimidazole-urea reported in the literature over the past 5 years are discussed. In addition, this review also examines molecular modeling and structure-activity relationship studies to elucidate their therapeutic potential, highlighting the contribution of hybrid benzimidazole derivatives to the development of effective drugs.
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2025-11-05
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41163192
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Non-linear association between Life's Essential 8 and diabetic retinopathy: mediating role of depression in US adults with diabetes.
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Life's Essential 8 (LE8) is a comprehensive cardiovascular health (CVH) metric that is associated with chronic diseases. This study aimed to investigate the association between LE8 and diabetic retinopathy (DR) and the mediating role of depression in this association. We analyzed cross-sectional data from 3,815 adults with diabetes mellitus from the National Health and Nutrition Examination Survey (NHANES) (1999-2020). LE8 scores (0-100) were calculated based on diet, physical activity, nicotine exposure, sleep health, body mass index (BMI), blood lipid levels, blood glucose levels, and blood pressure. DR was diagnosed using retinal imaging or self-reports. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Weighted logistic regression and mediation analysis were performed. In addition, machine learning (Shapley additive explanation [SHAP]) was used to explain the importance ranking of variables. Weighted logistic regression models revealed a significant negative association between LE8 scores and the risk of DR. The LE8 score had strong, dose-dependent protective effects against DR, with each 10-point increase in the score being associated with a 2% reduction in the risk of DR (odds ratio [OR] = 0.98, P < 0.0001) across adjusted models. A threshold effect was observed at the LE8 score of 73.12. The protective effect of the LE8 score was significant below this threshold (OR1 = 0.98, P < 0.0001), whereas it was diminished above this threshold (OR2 = 1.06, P = 0.097). Mediation analysis indicated that PHQ-9 scores mediated 13.66% of the total effect of LE8 (P < 0.0001). SHAP analysis showed that blood glucose levels (35.5% importance) had the greatest impact on risk prediction, followed by modifiable behaviors such as physical activity (18.0%) and sleep health (13.5%). LE8 scores are negatively associated with the risk of DR in US adults with diabetes mellitus, and this association is partially mediated by depressive symptoms. Longitudinal studies are warranted to validate causality and elucidate the underlying mechanisms. Interventions targeting both metabolic and mental health may reduce the disease burden of DR.
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2025-10-29
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41173028
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Mid-term clinical outcomes of the unlinked type K-NOW total elbow arthroplasty.
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This study aimed to evaluate the mid-term clinical outcomes, complications, and survival rates of the unlinked K-NOW (Teijin Nakashima Medical, Japan) total elbow arthroplasty (TEA), focusing on the use of cementless fixation. This retrospective study included 41 elbows in 37 patients who underwent primary TEA using unlinked K-NOW between April 2012 and March 2021, with a minimum follow-up of two years. Surgical approaches included the lateral paraolecranon (LPO) and triceps-off approaches. Clinical evaluations included range of motion (ROM) and Mayo Elbow Performance Score (MEPS). Complications were recorded, and Kaplan-Meier survival analysis was performed, with aseptic loosening and revision surgery as endpoints. The mean patient age was 68.4 years (SD 11.6), and the mean follow-up period was 4.7 years (2.1 to 10.1). The LPO approach was used in 35 elbows (85.4%), and cementless fixation was applied to 41 humeral components (100%) and 35 ulnar components (85.4%). Among patients with ≥ five years of follow-up (n = 16), significant improvements were observed in ROM (extension, from -38° to -19°; flexion, from 107° to 130°; pronation, from 55° to 72°; supination, from 62° to 73°; p < 0.001), and MEPS (from 48 to 93 points; p < 0.001) at five years postoperatively. Complications occurred in six elbows (14.6%): three elbows (7.3%) with aseptic loosening and three elbows (7.3%) with periprosthetic fractures; no postoperative dislocation was observed. Revision surgeries were required in two elbows (4.9%). Kaplan-Meier survival rates were 92.7% (95% CI 84.7 to 100) at five years for loosening, and 97.1% (95% CI 91.4 to 100) at five years for revision. All aseptic loosening occurred within three months postoperatively. The unlinked K-NOW with cementless fixation, mostly using the LPO approach, demonstrated favourable outcomes with improved ROM and MEPS, a low complication rate, and promising survival. In cases with severe osteoporosis or bone-implant instability, cemented fixation or a triceps-off approach may help reduce the risk of early complications.
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2025-11-01
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41190752
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Construction and validation of a risk prediction model for secondary acute kidney injury in patients with acute upper gastrointestinal bleeding.
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Objective Acute upper gastrointestinal bleeding (AUGIB) is one of the most common critical conditions in clinical practice and is characterized by rapid progression and a high incidence of secondary acute kidney injury (AKI). This study aimed to analyze the clinical characteristics of patients with AUGIB, identify related risk factors for secondary AKI, and develop a predictive model for AKI risk in this patient population. Methods A retrospective analysis was conducted on 300 patients with AUGIB admitted to our department. Patients were categorized based on the occurrence of AKI within 7 days. Univariate analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression were used for feature selection, followed by multivariable logistic regression to construct a predictive model. The model's performance was rigorously evaluated through bootstrap internal validation, calibration curves, and decision curve analysis (DCA). Results Seven independent risk factors were identified and incorporated into the SCORE-AKI: a history of renal insufficiency, hypertension, shock index > 1, Glasgow Coma Scale score ≤14, hemoglobin < 60 g/L, platelet count < 50 × 109/L, and serum creatinine > 103 μmol/L. The model showed strong discrimination with a bootstrap-corrected area under the curve (AUC) of 0.808, which was significantly superior to the Glasgow Blatchford score (AUC: 0.722, p < 0.001). The model also demonstrated excellent calibration and a positive net benefit across clinical decision thresholds. Conclusion The SCORE-AKI model is a accurate, well-calibrated, and clinically useful tool that outperforms the GBS for predicting secondary AKI risk in patients with AUGIB, potentially aiding in early risk stratification and preventive intervention.
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2025-11-05
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41193287
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Uniform and reliable assessment of bone union on radiographs in osteotomies around the knee: a novel classification system.
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To evaluate the inter- and intra-rater reliability of the Unified Bone Union (UBU) classification for assessing time-dependent bone healing on radiographs in osteotomies around the knee, including negative union signs. Secondary aims included assessing union progression over time, applicability across osteotomy types, and correlation between radiographic and CT-based UBU scores. The UBU classification assesses bone healing on anteroposterior radiographs in three anatomical zones, graded from phase 0 (no callus) to phase 3 (bridging callus), including radiological negative union signs. Radiographs (n = 110) from 38 medial opening-wedge high tibial osteotomy patients were retrospectively reviewed twice by three independent raters. Inter- and intra-rater reliability were assessed using quadratic-weighted kappa (κ). Percent agreement was calculated for classification modifiers. Time-dependent changes in union were analyzed. Reliability was also tested across osteotomy types. Correlation between 6-month radiographic and CT-based UBU scores was determined using Spearman's rho. Interrater reliability was substantial (κ 0.74-0.79), while intra-rater reliability showed almost perfect agreement (κ 0.78-0.98). Modifier agreement was good (inter-rater: 91-98 %; intra-rater: 89-95 %). The UBU score increased over time. The UBU showed substantial interrater reliability (κ = 0.75) across various osteotomy types. A strong correlation was found between radiographic and CT-based UBU scores (r = 0.82, p < 0.01). The UBU classification provides a reliable and standardized method for evaluating bone union after osteotomies around the knee. It incorporates negative union signs and demonstrates strong inter- and intra-rater agreement, as well as strong correlation with CT imaging. Further research should validate its diagnostic accuracy and clinical utility.
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2025-11-04
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41185286
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Neem oil emulsions stabilized by natural and synthetic emulsifiers: a study on physical stability and antifungal activity.
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Neem oil (NO) is a plant-derived bioactive compound with known antimicrobial properties. Incorporating NO into oil-in-water (O/W) emulsions can improve its stability, bioavailability, and allow controlled release. This study developed and characterized O/W emulsions using NO as the dispersed phase and active agent. Emulsions were formulated with natural emulsifiers (soy lecithin - SL, pea protein - PP), a synthetic emulsifier (Tween 80 - T80), and their combinations. Over 21 days, formulations were analyzed for chemical interactions, droplet size (D<sub>4,3</sub>), polydispersity (Span), zeta potential (ZP), microstructure, color, kinetic stability, and antifungal activity (AFA) against Alternaria alternata and Penicillium expansum. All emulsions showed stable chemical interactions and ZP values above |38 mV|. D<sub>4,3</sub> ranged from 0.59 to 2.01 μm, influenced by emulsifier type. Thermally treated PP in alkaline conditions produced stable, slightly polydisperse emulsions for 14 days, while SL led to larger droplets and instability. PP:T80 and T80:SL combinations showed synergistic effects and good stability, unlike PP:SL, which resulted in unstable emulsions. The PP-only emulsion had the highest AFA, inhibiting P. expansum (85.06 %) and A. alternata (79.97 %). These findings highlight the critical role of emulsifier selection in enhancing the stability, controlled release, and antifungal efficacy of NO in emulsified systems.
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2025-12-01
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41164666
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An <i>In-vitro</i> Assessment of Potassium Iodide and Glutathione on Color Change Caused by Silver Diamine Fluoride Treatment.
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To assess and contrast the impact of glutathione (GSH) and potassium iodide (KI) on tooth discoloration brought on by silver diamine fluoride (SDF) treatment on primary incisors. Standardized 2 mm × 2 mm (depth × width) of cavities were made on labial surface of each specimen, and artificial caries was created on 40 extracted primary incisors and divided into four groups based on the solution used as follows: group 1 - SDF, group 2 - SDF + saturated KI, group 3 - SDF + GSH, and group 4 - distilled water. The color assessment was recorded on days 1, 7, and 14 by using a spectrophotometer. SDF caused maximum staining. Staining in groups 2 and 3 was significantly less (<i>P</i> < 0.05) compared to SDF, while group 3 showed the least staining at days 1 and 7, but the staining increased gradually and had no statistical difference at 14 days when compared to group 2. The use of GSH along with SDF helps in reducing the discoloration.
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2025-09-01
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41211647
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The association of periodontal inflammation and inflammatory markers with cognitive dysfunction: A case-control study.
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This study investigated the association of inflammatory markers in saliva, plasma, and cerebrospinal fluid (CSF) with cognitive decline and periodontitis. Patients with Alzheimer disease (AD, n = 52), mild cognitive impairment (MCI, n = 51), subjective cognitive decline (SCD, n = 51), and controls (n = 76) between 50 and 80 years were included. Participants underwent an oral examination, and blood and stimulated saliva were collected. In addition, CSF samples were collected from patients but not controls. Levels of interleukin (IL)-1β, IL-8, IL-10, IL-17A, and tumor necrosis factor-alpha (TNF-α) were analyzed by multiplex immunoassays. Increased salivary levels of IL-1β, IL-10, and IL-17A were found in MCI compared to controls, while in plasma increased IL-8 levels were seen in all 3 patient groups compared to controls (p < 0.001). TNF-α plasma levels were higher in SCD and AD (p < 0.05). IL-17A levels in CSF were higher in participants with no/mild periodontitis compared to generalized periodontitis (p = 0.023). Participants with severe periodontitis showed higher levels of IL-8 both in saliva (p = 0.027) and plasma (p < 0.001), as well as higher TNF-α levels in plasma (p = 0.041). Inflammation markers could indicate an increased risk for cognitive decline, especially in cases of more severe periodontitis. Evidence has indicated an association between periodontitis and cognitive impairment. Hence, this study investigated whether inflammatory markers in saliva, plasma, and cerebrospinal fluid are associated with cognitive decline. Cases with mild or more severe signs of cognitive impairment had more signs of periodontal disease. Levels of some, but not all, inflammation markers were elevated among patients compared to cognitively healthy controls. Oral inflammation could indicate an increased risk for cognitive decline, and chronic inflammation may act as a common pathway. Early periodontal intervention and maintaining oral health may contribute to cognitive well-being.
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2025-11-10
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41191323
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Cerebral microbleeds aggravate severity of motor function, cognitive and emotional status in Parkinson's disease.
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Cerebral microbleeds (CMBs) are highly prevalent in patients with Parkinson's disease (PD), but their impact on clinical symptom severity and genetic association remains unclear. This study investigates the relationship between CMBs and PD severity. We recruited patients with PD from the outpatient clinic and inpatient wards of the First Affiliated Hospital of Chongqing Medical University. All participants had undergone susceptibility-weighted imaging (SWI) and had complete clinical assessments. Participants were categorized into groups based on their CMB count. We subsequently analyzed the risk factors for CMBs and examined the correlations between CMB burden and motor, cognitive, and emotional function, respectively. Furthermore, utilizing a genome-wide association study (GWAS) dataset, we investigated the association between genetic susceptibility to CMBs and PD severity preliminarily by Mendelian randomization (MR). Among 158 patients with PD, 53 (33.5%) were found to have CMBs. Age, disease duration, and hypertension were independently associated with the presence of CMBs (p < 0.05). Multiple linear regression analysis indicated that a higher CMB burden was associated with poorer motor function and the presence of anxiety disorders. To gain deeper insight into the relationship between CMB and severity of PD, MR analysis further suggested that genetic susceptibility to CMBs is potentially causally linked to worse motor function (OR = 1.301, p = 0.047), lower scores on the Montreal Cognitive Assessment (MoCA) (OR = 0.207, p = 0.021) and the Mini-Mental State Examination (MMSE) (OR = 4.915, p = 1.63E-08), as well as an increased risk of dementia in PD (OR = 4.915, p = 1.63E-08). The high prevalence of CMBs was associated with age, disease duration, and hypertension. Furthermore, our MR analysis provides preliminary evidence that a higher CMB burden may exacerbate the severity of Parkinson's disease.
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2025-11-05
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41180305
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Single-Nuclei RNA Sequencing Shows the Engagement of PPAR-Delta Target Genes Primarily in Hepatocytes and Cholangiocytes by the Selective PPAR-Delta Agonist Seladelpar.
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The selective peroxisome proliferator-activated receptor delta (PPARD) agonist seladelpar reduces liver injury and modulates bile acid metabolism in preclinical models. Seladelpar was recently approved for the secondary treatment of primary biliary cholangitis (PBC). Despite its beneficial effects for liver diseases, the target cells of seladelpar on a single-cell level remain unknown. This study is aimed at investigating the effect of seladelpar on single liver cells. CD-1 mice were gavaged with vehicle or seladelpar (10 mg/kg body weight), and the liver was harvested 6 h later. Single-nuclei RNA sequencing (snRNA-seq) analysis showed the engagement of PPARD target genes primarily in hepatocytes and cholangiocytes by seladelpar. The top two upregulated genes, <i>Ehhadh</i> and <i>Cyp4a14</i>, are related to fatty acid metabolism and were increased in hepatocytes, cholangiocytes, and Kupffer cells. <i>Abcb4</i>, an important canalicular transporter with hepatoprotective effects, was significantly upregulated in hepatocytes. We confirmed upregulated <i>Abcb4</i> gene expression in seladelpar-treated primary mouse hepatocytes isolated from C57BL/6 mice. We further incubated nonparenchymal liver cells with seladelpar. Although there was a significant increase in the PPARD-responsive genes <i>Pdk4</i> and <i>Angptl4</i> in cholangiocytes, Kupffer cells, and hepatic stellate cells, seladelpar did not exert specific liver-protective effects in these cell types. The selective PPARD agonist seladelpar induced PPARD-responsive genes primarily in hepatocytes and cholangiocytes. Seladelpar upregulated <i>Abcb4</i> in hepatocytes, which might contribute to its beneficial effects in cholestatic liver disorders.
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2025-01-01
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41175199
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Heterogeneity in clinically diagnosed type 1 diabetes: characterising a unique cohort with maintained C-peptide secretion in Ghana.
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In sub-Saharan Africa, type 1 diabetes is typically diagnosed clinically, which can be challenging due to atypical diabetes presentations such as ketosis-prone type 2 diabetes or type 2 diabetes in the absence of overweight and obesity. C-peptide, a marker of residual insulin secretion capacity, is crucial for understanding these variations but understudied in the region. Here, we investigated whether C-peptide measurement and concomitant genetic, autoimmune and metabolic characterisation of individuals with clinically diagnosed type 1 diabetes confirm diabetes classification and highlight population-specific features. In this case-control study from Ghana, we recruited 266 individuals with clinically diagnosed and insulin-treated long-term type 1 diabetes and 266 healthy control individuals. We compared clinical features, HLA class II haplotypes, autoantibodies, and inflammatory and metabolic serum profiles across control and patient groups classified by random C-peptide levels: low (<0.2 nmol/l), mid (0.2-0.6 nmol/l) and high (>0.6 nmol/l). Only 28.9% of individuals with clinically diagnosed type 1 diabetes had low C-peptide concentrations. They were the youngest and leanest group, with higher frequencies of HLA class II risk haplotypes and GAD and ZnT8 autoantibodies compared with all other groups. By contrast, 34.6% and 36.5% had mid-range or high C-peptide levels, respectively. These subgroups resembled the control group in terms of low autoantibody titres and one protective HLA class II haplotype. Ketosis at onset was most prevalent in individuals with high C-peptide. Serum proinflammatory biomarkers differed between individuals with diabetes and control participants, but not between C-peptide subgroups. Aromatic and branched-chain amino acids varied between diabetes subgroups and positively correlated with C-peptide levels. Maintained C-peptide levels in two-thirds of individuals with long-term type 1 diabetes in Ghana, combined with the absence of autoantibodies and HLA risk association, highlight the necessity for better differentiation from atypical diabetes presentations to optimise patient care and improve health outcomes in resource-limited settings.
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2025-11-01
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41188435
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Acute effect of light and time of day on thermal physiology, perception, and behavior.
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Implementing novel, human-centric building control strategies that account for the interaction of multidomain factors, light, temperature, and time of day, can enhance occupant comfort and promote energy savings. However, their successful implementations require a robust framework that clearly explains the physiological mechanisms through which light exposure influences thermal perception and evaluation. To date, most studies have primarily relied on the hue-heat hypothesis, which attributes changes in thermal assessment solely to visual color associations, overlooking the physiological impact of light, particularly blue-enriched bright light, on the circadian rhythm and thermoregulation. In this study, we investigated the influence of light intensity on thermal physiology, perception, and behavior within a circadian context, employing skin temperature measurements, subjective questionnaires, and fan-use behavior as outcome measures. 20 healthy adults participated in four experimental sessions combining two illuminance levels (bright vs. dim, with identical spectral composition) at two times of day (07:00 and 14:00) under warm conditions, both steady-state and fan-induced dynamic ones. Results showed that skin temperature followed its natural circadian rhythm, being lower in the early morning than at midday. Notably, bright light exposure significantly suppressed the circadian rise in skin temperature in the morning, shifted thermal sensation votes from slightly warm towards neutral, and improved thermal comfort votes compared to dim light or midday exposure. This effect was evident under steady-state warm conditions and persisted following fan use. In contrast, under the fan-induced slightly cool condition, neither light intensity nor time of day significantly affected thermal assessment. These findings underscore the fundamental role of circadian physiology in thermal comfort and suggest that strategically timed light and thermal exposure can optimize comfort by aligning ambient conditions with the body's internal rhythms.
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2025-11-04
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41167217
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Physical examinations and whole-body imaging versus physical examinations alone during follow-up after radical surgery of stage IIB-C and III cutaneous malignant melanoma (TRIM): an interim analysis of a multicentre, randomised, phase 3 trial in Sweden.
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In several countries, whole-body imaging has been introduced in the routine follow-up of individuals with high-risk cutaneous malignant melanoma after surgery. However, there is scarce evidence that earlier detection of recurrent disease by regular scanning improves survival. In this interim analysis, we investigated whether imaging in the follow-up programme for high-risk cutaneous malignant melanoma improves survival and assessed whether the study should continue to include participants. TRIM is a multicentre, randomised, phase 3 trial in Sweden. Eligible participants are aged 18 years and older with sufficient renal function for intravenously contrast-enhanced CT and are expected to be fit for treatment in case of recurrence. After radical surgery of stage IIB-C and III cutaneous malignant melanoma, participants were randomly assigned (1:1, stratified by tumour stage and method of radiological assessment) to 3 years of follow-up by physical examinations alone (standard group) or to physical examinations plus whole-body imaging with CT or [<sup>18</sup>F]fluorodeoxyglucose-PET-CT at baseline, 6, 12, 24, and 36 months (experimental group). The goal is to include 1300 participants. The primary endpoint is overall survival at 5 years and will be reported in the final analysis when data are mature. In this interim report, no endpoints were predefined; we present overall survival, relapse-free survival, locoregional relapse-free survival, and distant metastasis-free survival, analysed by intention to intervene. This study is registered with ClinicalTrials.gov, NCT03116412, and recruitment is ongoing. Between June 8, 2017, and July 28, 2023, 983 participants were randomly allocated to the standard (n=498; 296 [59%] male, 202 [41%] female) or experimental (n=485; 309 [64%] male, 176 [36%] female) group. There were no statistically significant differences in overall survival (not reached [NR; 95% CI NR-NR] vs NR [NR-NR]; hazard ratio [HR] 1·04 [95% CI 0·71-1·51], p=0·85) or distant metastasis-free survival (NR [NR-NR] vs NR [NR-NR]; HR 1·20 [0·89-1·64], p=0·24) between the groups at a median follow-up time of 33·6 months (IQR 16·3-49·8). 3-year overall survival rates were 88·2% (95% CI 85·0-91·6) in the standard group versus 87·7% (84·3-91·3) in the experimental group and distant metastasis-free survival was 81·6% (77·9-85·6) in the standard group versus 79·3% (75·3-83·5) in the control group. This interim analysis indicated that there is no benefit from imaging in the follow-up programme for individuals with high-risk cutaneous malignant melanoma. However, only a few participants have completed the follow-up time of 5 years, and the numerical difference between the study groups in distant metastasis-free survival motivates us to continue the study according to protocol. Stiftelsen Onkologiska Klinikens i Uppsala Forskningsfond and Uppsala University Hospital.
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2025-11-01
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41169950
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Adverse events beyond the RUBY trial: reporting immunotherapy-associated myocarditis, myositis, and myasthenia gravis in a real-world endometrial cancer case.
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To report a rare case of immune checkpoint inhibitor (ICI)-associated myocarditis, myositis, and myasthenia gravis (MMM syndrome) in a patient with advanced endometrial cancer treated with dostarlimab, highlighting the diagnostic and therapeutic challenges, in addition to the importance of biomarker-informed treatment selection. We report the case of a 75-year-old woman with unresectable stage IIIC2 endometrial adenocarcinoma and mismatch repair (MMR) deficiency treated with carboplatin and paclitaxel, followed by dostarlimab. After initiation of dostarlimab, the patient presented with neuromuscular and cardiac symptoms, leading to the diagnosis of myocarditis, myositis, myasthenia gravis (MMM) syndrome requiring hospitalization. A multidisciplinary care including neurologic, cardiac, and critical care management was required. The patient developed MMM syndrome 81 days after starting dostarlimab, presenting with bilateral ptosis, dysphagia, diplopia and respiratory compromise. Evaluation revealed elevated troponins, elevated creatine kinase, and a positive acetylcholine receptor antibody. Cardiac MRI confirmed myocarditis. Management included high-dose steroids, mycophenolate, IVIG, abatacept, and tofacitinib, with initial stabilization. MMM syndrome is a rare but life-threatening complication of ICI therapy. Early recognition and multidisciplinary management are crucial. This case underscores the importance of weighing the risks and benefits of initiating immunotherapy and utilizing biomarker-driven clinical decisions.
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2025-10-01
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41180056
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Lived experiences of individuals with cyberviolence: Understanding the nature of the dark side of social media use.
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The advancement in technology has given more people accessibility to internet and social media. Technological advances have led to the exponential rise of cybercrime, with an average of 7000 cases being reported in India every day in 2024. Given the potential harmful consequences, a thorough understanding of this phenomenon and the ways to address them is critically required. To explore the lived experience of cyberviolence and online victimization. The sample comprised of 14 individuals aged 18-30 years, who were the target of cyberviolence, recruited through snowball sampling. Data was collected through a semi-structured interview schedule that was subjected to thematic analysis. The key characteristics of cyberviolence perpetration were found to be the anonymity and power of perpetrator, availability of wider audience, its continuous nature, greater accessibility to the cyber victims, the inability to escape, ease of committing the crime, and difficulty in gathering evidence. These enable the perpetrators to commit different types of cyberviolence, including cyberbullying, online sexual harassment, identity theft, catfishing, and cyber grooming. The study sheds light on the rapidly emerging phenomenon of cyberviolence, operationalizes its definition, and outlines its key characteristics that likely act as facilitative factors for the perpetration of online violence.
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2025-01-01
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41196917
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Substituted cysteine modification and protection indicates selective interactions of the anesthetic photolabel pTFD-di-iPr-BnOH with α+/β- and α+/γ- transmembrane subunit interfaces of synaptic GABAA receptors.
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General anesthesia induced by etomidate, barbiturates and propofol is associated with positive modulation of synaptic αβγ GABAA receptors, inhibitory hetero-pentameric ligand-gated ion channels formed from homologous subunits arranged β-α-β-α-γ around a central gated chloride channel. Approaches based on mutations, amino-acid level analysis of photolabel incorporation, and cryo-electron micrography (cryo-EM) all indicate that etomidate binds selectively in two outer transmembrane β+/α- inter-subunit sites per receptor. These approaches also reveal that the potent barbiturate photolabel R-mTFD-MPAB binds selectively in homologous sites formed at α+/β- and γ+/β- interfaces. The anesthetic photolabel, pTFD-di-iPr-BnOH, was proposed to bind selectively in α+/β- and α+/γ- homologs of the etomidate sites, based largely on functional analysis of only 5 point mutations in α1β3γ2L receptors. To further test the interactions of receptor-bound pTFD-di-iPr-BnOH with outer transmembrane inter-subunit sites, we used voltage-clamp electrophysiology in substituted cysteine modification and protection (SCAMP) experiments at 8 residues located in the five homologous sites, focusing on α+ and γ- loci. Control SCAMP studies were performed using etomidate and R-mTFD-MPAB. Incorporation of single cysteine mutations (α1M236C, α1S280C, α1A291C, β3L231C, β3M286C, γ2I242C, γ2L246C, and γ2S301C) produced functional GABA-responsive receptors that retained sensitivity to pTFD-di-iPr-BnOH modulation and displayed increased GABA sensitivity following exposure to the covalent sulfhydryl modifier p-chloromercuribenzenesulfonate (pCMBS). In the presence of pTFD-di-iPr-BnOH, pCMBS modification effects were reduced (evidence of steric protection) in receptors with cysteine mutations in α+ , β-, and γ-, but not in α-, β+ , or γ+ interfacial loci. Protection patterns with etomidate and R-mTFD-MPAB mirrored prior results. SCAMP results further support the hypothesis that pTFD-di-iPr-BnOH binds selectively in α+/β- and α+/γ- interfacial sites that are homologs of the β+/α- etomidate sites.
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2025-01-01
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41166054
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Measurement of gamma-ray dose rate distribution at the Kindai university reactor using the thermoluminescent properties of BeO ceramic plates.
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The gamma-ray dose rate distribution at the Kindai University Reactor (UTR-KINKI) was measured using the thermoluminescent (TL) properties of beryllium oxide (BeO) ceramic plates. The reactor, operating at an extremely low thermal power of 1 W, is widely used for nuclear research, including radiation biology and detector development. In neutron-gamma mixed fields, determining the gamma-ray dose rate accurately is technically challenging due to the neutron sensitivity of conventional dosimeters. In this study, low-Na BeO ceramic thermoluminescence dosimeters (TLDs) were employed to selectively measure gamma-ray dose rates in the irradiation hole of UTR-KINKI, without the need for neutron correction. A comparative assessment was conducted using Na-doped BeO powder TLDs, and thermal neutron flux measurements were performed using a Li-glass scintillator. The results demonstrated that the height-dependent trend of the gamma-ray dose rate distribution was consistent with previous measurements obtained via paired ionization chambers. However, the absolute values of the gamma-ray dose rates measured with the BeO ceramic TLDs were approximately 10-30% higher than those determined by the paired ionization chamber. This discrepancy is likely due to neutron sensitivity considerations in previous studies. The gamma-ray dose rate at the reactor center was evaluated as approximately 24 cGy h<sup>-1</sup>. This study highlights the applicability of BeO ceramic TLDs for gamma-ray dosimetry in mixed radiation fields, offering a neutron-insensitive alternative for precise dose measurements in reactor environments.
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2025-10-30
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41180005
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Thalidomide as an Adjunctive Therapy for HIV-Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome: A Case Series.
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A small proportion of people living with human immunodeficiency virus (HIV) who have tuberculosis-related immune reconstitution inflammatory syndrome (tuberculosis-IRIS) have prolonged and complicated courses and experience poor response to corticosteroid therapy, relapse after withdrawing, or intolerability demonstrating a need for alternative immunomodulatory options. Thalidomide has been shown to have immunomodulatory effects, primarily in neurological tuberculosis in children, but there is little description of its use in adult patients. We describe the clinical course in 7 adult patients with complicated HIV-associated tuberculosis-IRIS treated with thalidomide. The clinical manifestations included central nervous system tuberculosis (n = 4) , tuberculous adenitis (n = 2), and recurrent tuberculous psoas collection (n = 1). All patients were given thalidomide (100 mg) for 6-12 months, with favorable clinical outcomes and no adverse effects. Thalidomide dosed at 100 mg/d remains an agent with clinical utility in this small subset of patients, and further research to determine optimal dosing and duration could be beneficial.
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2025-11-01
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41202991
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A virtual mind-body exercise program during breast radiation: Results from a randomized controlled basket trial.
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National guidelines recommend fitness and mind-body exercise to reduce cancer-related fatigue, but substantial barriers to implementation exist. Virtual programs offer a scalable approach to address this gap. This study aims to evaluate efficacy of a virtual fitness and mind-body exercise program (Integrative Medicine at Home, IM@Home) in reducing fatigue in patients undergoing radiation therapy (RT) for breast cancer. A prospective randomized controlled patient-reported outcome (PRO)-basket clinical trial was conducted. Patients undergoing breast RT who reported moderate or greater fatigue were randomly assigned 1:1 ratio to either IM@Home, which provided live virtual fitness and mind-body exercise classes, or enhanced usual care (EUC). The primary outcome, fatigue, was measured using total Brief Fatigue Inventory (BFI), a composite score including severity and impact on daily functioning, weekly over 12 weeks. Secondary outcomes included Insomnia Severity Index (ISI), Edmonton Symptom Assessment Scale (ESAS), and Hospital Anxiety and Depression Scale (HADS) collected every 4 weeks. Statistical analysis included linear mixed models to compare group differences over time using statistical significance threshold of p < 0.05. Among 73 enrolled patients, 35 were randomly assigned to IM@Home and 38 to EUC. At week 12, patients in the IM@Home group had significantly less fatigue compared to those in the EUC group (2.06 vs 2.79, p=0.009). Compared to EUC, patients in the IM@Home group showed greater reductions in insomnia (p=0.005), symptom distress (p=0.013), and depression (p=0.04) but not anxiety (p=0.14). The IM@Home program significantly reduced fatigue and co-morbid symptoms among women with breast cancer undergoing RT. Future research is needed to confirm these findings, explore mechanisms of the observed benefit, and evaluate scalability as well as barriers and facilitators to implementation. NCT05053230.
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2025-11-05
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41171604
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Three-dimensional visualisation of human ovarian follicles using a whole-mount immunolabelling and optical tissue clearing method.
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To more accurately classify human ovarian follicles by developing a novel methodology with three-dimensional visualisation using whole-mount immunolabelling and optical tissue clearing techniques. A whole-mount immunolabelling protocol combined with optical tissue clearing was applied to human ovarian tissue for three-dimensional follicle analysis. Key markers, including DAPI for nuclear staining, DDX4 for oocyte-specific labelling, and LAMININ for basal membranes, were used to visualise follicular structures. The tissues underwent a clearing process to enable confocal z-stack imaging to obtain detailed three-dimensional data. Ovarian cortical tissue from three paediatric patients (aged 9-12 years) who had not undergone chemotherapy treatment was collected. The tissue was dissected into small fragments and stained to identify viable follicles. Follicle and oocyte size, as well as granulosa cell size and type, were assessed across multiple dimensions (XY, XZ, YZ planes). Follicles were classified as primordial or transitional based on granulosa cell characteristics. Three-dimensional analysis across XY, XZ, and YZ planes revealed that 58% of follicles, initially classified as primordial using conventional two-dimensional methods, were misidentified as transitional due to the presence of cuboidal granulosa cells that were only detectable in multi-plane analysis. Moreover, three-dimensional analyses revealed significant differences in the number and size of cuboidal granulosa cells detected on transitional follicles. This study presents a novel whole-mount immunolabelling and optical tissue clearing methodology for accurate three-dimensional visualisation and classification of human ovarian follicles. This technique improves the accuracy of follicle staging and provides a valuable tool for future research into ovarian function, reproductive health, and conditions impacting follicle development. In this study, we explored a new method for examining ovarian follicles - structures that contain the immature eggs - within human ovarian tissue. Traditional methods, which rely on two-dimensional imaging, can lead to mistakes in classifying the development of these follicles due to their spherical shape. To address this, we developed techniques to visualise the ovarian tissue in three dimensions. Using ovarian tissue from three patients, the tissue was processed using techniques called whole-mount immunolabelling (to detect structures) followed by optical clearing (to visualise the structures) and then analysed using microscopy. This enabled us to create detailed 3D images that showed the structures of the immature eggs and follicles across different planes of view. We discovered that conventional 2D assessments misclassified nearly 60% of the follicles, as certain developmental characteristics were only visible in the 3D images. This innovative approach marks the first time such detailed 3D imaging has been applied to human ovarian follicles. It not only enhances the accuracy of classifying follicle stages but also holds potential for improving fertility preservation techniques in the future. Overall, the study highlights the benefits of using modern imaging methods to gain better insights into ovarian health and development.
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2025-10-01
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