Discovery and biological evaluation of potent 2-trifluoromethyl acrylamide warhead-containing inhibitors of protein disulfide isomerase.

Protein disulfide isomerase (PDI) regulates multiple protein functions by catalyzing the oxidation, reduction, and isomerization of disulfide bonds. The enzyme is considered a potential target for treating thrombosis. We previously developed a potent PDI inhibitor, CPD, which contains the propiolamide as a warhead targeting cysteine residue in PDI.

Comparison of urinary excretion patterns among exposures to cosmetic preservative, herbicide, and nootropic stimulant in anti-doping analysis.

Doping with meclofenoxate, a nootropic stimulant prohibited in-competition by the World Anti-Doping Agency (WADA), is identified through the primary marker of urinary 4-chlorophenoxyacetic acid (4-CPA). However, the presence of 4-CPA can also arise from permissible sources. This study ventured into comparing urinary excretion patterns among exposures to permitted chemicals (chlorphenesin and 4-CPA) and the banned stimulant (meclofenoxate) and interpreting the analytical findings according to the reporting requirements.

Topical Vancomycin Paste Over the Sternal Edge During Cardiac Surgery: Effects of Renal Function and Body Size on Systemic Exposure.

Purpose: Intraoperative topical vancomycin has been widely used in several surgical fields to prevent wound infection. However, there have been limited studies on the systemic exposure of topical vancomycin. The aim of this study was to investigate systemic exposure after topical vancomycin over the sternal edge in cardiac surgical patients.

Serial changes in metabolic dysfunction-associated steatotic liver disease after sleeve gastrectomy and their associations with abdominal adiposity: a prospective cohort study.

Background: Little is known about the associations between changes in hepatic steatosis and changes in abdominal adiposity after metabolic bariatric surgery.

Objectives: To evaluate the serial changes in hepatic steatosis and abdominal adiposity following sleeve gastrectomy (SG).

Setting: University hospital, Taiwan.

The factors associated with clozapine polypharmacy for schizophrenia patients discharged from a large public psychiatric hospital in Taiwan, 2006-2021.

Clozapine treatment continues to be recognized as the gold standard for managing treatment-resistant schizophrenia. Combining clozapine with other antipsychotics (i.e.

Effectiveness of Interventions to Disease Management Programs of Patients with Heart Failure: A Systematic Review and Meta-Analysis.

Heart failure (HF) prevalence is rising due to population aging and increasing risk factor incidence, thereby posing a significant global public health challenge. Disease management programs (DMPs) play a crucial role in managing HF and optimizing postevent health outcomes. Through a systematic review and meta-analysis, this study aimed to evaluate the effectiveness of DMPs following an HF event.

Parental health belief model constructs associated with oral health behaviors, dental caries, and quality of life among preschool children in China: a cross-sectional study.

Background: Early childhood caries (ECC) is a prevalent health problem that negatively affects both overall health and oral health-related quality of life (OHRQoL). This study investigated the association between health belief model (HBM) constructs and oral health behaviors, dental caries, and OHRQoL in preschool children in China.

Methods: A total of 1562 preschool children aged 3 to 6 years were recruited from six public kindergartens in Hangzhou, Zhejiang Province, by using stratified cluster sampling.

Trans-differentiation of Jdp2-depleted Gaba-receptor-positive cerebellar granule cells to Purkinje cells.

The Jun dimerization protein (Jdp2) gene is active in mouse cerebellar granule cells and its protein product plays a crucial role in the formation of the cerebellum lobes through programmed cell death. However, the role of Jdp2 in cellular differentiation and pluripotency in the cerebellum, and the effect of the antioxidation reaction on cell plasticity, remain unknown. N-acetyl-L-cysteine (NAC) induced the early commitment of the differentiation of granule cell precursors (GCPs) to neurons, especially Purkinje cells, via the γ-aminobutyric acid type A receptor α6 subunit (Gabra6) axis; moreover, Jdp2 depletion enhanced this differentiation program of GCPs.

Metabolic shifts in lipid utilization and reciprocal interactions within the lung metastatic niche of triple-negative breast cancer revealed by spatial multi-omics.

The Triple-Negative Breast Cancer (TNBC) subtype constitutes 15-20% of breast cancer cases and is associated with the poorest clinical outcomes. Distant metastasis, particularly to the lungs, is a major contributor to the high mortality rates in breast cancer patients. Despite this, there has been a lack of comprehensive insights into the heterogeneity of metastatic tumors and their surrounding ecosystem in the lungs.

Effectiveness Study of a Cultural Adaptation of Cognitive-Behavioural Therapy-Based Application for Depressive Symptoms in College Students: A Randomised Controlled Trial.

Introduction: Studies on mental health applications among college students lack empirical evidence regarding mobile application usage's intensity, duration and frequency.

Aim: To evaluate the effectiveness of a cognitive-behavioural therapy (CBT)-based mobile application in ameliorating depressive symptoms among college students.

Methods: A randomised controlled trial was conducted at three universities.

Enhancing pharmacogenomic data accessibility and drug safety with large language models: a case study with Llama3.1.

Pharmacogenomics (PGx) holds the promise of personalizing medical treatments based on individual genetic profiles, thereby enhancing drug efficacy and safety. However, the current landscape of PGx research is hindered by fragmented data sources, time-consuming manual data extraction processes, and the need for comprehensive and up-to-date information. This study aims to address these challenges by evaluating the ability of Large Language Models (LLMs), specifically Llama3.

Exploring the Synergistic Effects of Erinacines on Microglial Regulation and Alzheimer's Pathology Under Metabolic Stress.

Background: Hericium erinaceus mycelium and its constituents, erinacines A and S, have shown neuroprotective effects in APP/PS1 transgenic mice; however, the precise mechanisms by which they modulate microglial phenotypes remain unclear. Our study is the first to explore the effect of erinacines on microglia morphology and the underlying mechanisms using a novel primary mixed glia cell model and advanced bioinformatic tools. Furthermore, we emphasize the clinical relevance by evaluating erinacines in a metabolically stressed APP/PS1 mouse model, which more accurately reflects the complexities of human Alzheimer's disease (AD), where metabolic syndrome is a common comorbidity.

Perspectives of the medical oncologist regarding adjuvant chemotherapy for pancreatic cancer: An international expert survey and case vignette study.

Introduction: Adjuvant chemotherapy improves survival in patients with resected pancreatic ductal adenocarcinoma (PDAC). The decision to initiate chemotherapy involves both patient and physician factors, decision-specific criteria, and contextual considerations. This study aimed to assess medical oncologists' views on adjuvant chemotherapy following pancreatic resection for PDAC.

Recent Range Expansion and Genomic Admixture in a Kleptoparasitic Spider, Argyrodes lanyuensis: A Case of Adaptive Introgression on Small, Isolated Islands of the Taiwan-Philippine Transition Zone?

Adaptive introgression involves the acquisition of advantageous genetic variants through hybridisation, which are subsequently favoured by natural selection due to their association with beneficial traits. Here, we analysed speciation patterns of the kleptoparasitic spider, Argyrodes lanyuensis, through genomic analyses and tested for possible genetic evidence of adaptive introgression at the Taiwan-Philippines transition zone. Our study used highly polymorphic SNPs to demonstrate that speciation occurred when the Hualien (on Taiwan Island + Green Island) and Orchid Island + Philippine lineages separated during the early to mid-Pleistocene.

Imipenem pharmacokinetics/pharmacodynamics in preclinical hollow fiber model, dose-finding in virtual patients, and clinical evidence of efficacy for Mycobacterium abscessus lung disease.

Background: Guideline-based therapy (GBT) for Mycobacterium abscessus (Mab) lung disease achieves sputum culture conversion rates (SCC) of 35%. This poor GBT efficacy is mirrored in the hollow fiber system model of Mab (HFS-Mab). While imipenem is part of GBT, biological effect with or without β-lactamase inhibitors, is unproven.

Computer-aided endoscopic diagnostic system modified with hyperspectral imaging for the classification of esophageal neoplasms.

Introduction: The early detection of esophageal cancer is crucial to enhancing patient survival rates, and endoscopy remains the gold standard for identifying esophageal neoplasms. Despite this fact, accurately diagnosing superficial esophageal neoplasms poses a challenge, even for seasoned endoscopists. Recent advancements in computer-aided diagnostic systems, empowered by artificial intelligence (AI), have shown promising results in elevating the diagnostic precision for early-stage esophageal cancer.

Ultrasensitive protein-level detection for respiratory infectious viruses.

Influenza virus, adenovirus, and respiratory syncytial virus cause major respiratory infections. These infections have similar initial symptoms making it difficult to differentiate them based on symptoms alone. PCR is currently used as the standard diagnostic test for these infections, however, it has its limitations such as non-specific and false-negative amplifications, high cost, and the inability to distinguish between a live or dead virus.

A 11B-NMR Method for the In Situ Monitoring of the Formation of Dynamic Covalent Boronate Esters in Dendrimers.

The in situ monitoring of dynamic covalent macromolecular boronate esters represents a difficult task. In this report, we present an in situ method using fluoride coordination and B NMR spectroscopy to determine the amount of boronate esters in a mixture of boronic acids and cis-diols. With fluoride coordination, the boronic acid and boronate esters afforded trifluoroborate and fluoroboronate esters, giving identical resonances at 3 and 9 ppm in the B NMR spectra.

Resveratrol Butyrate Esters Reduce Hypertension in a Juvenile Rat Model of Chronic Kidney Disease Exacerbated by Microplastics.

Background: Resveratrol is recognized as a promising nutraceutical with antihypertensive and prebiotic properties; however, its bioavailability in vivo is limited. To enhance its bioactivity, we developed resveratrol butyrate esters (RBEs). This study investigates whether RBEs can mitigate hypertension induced by chronic kidney disease (CKD) and exacerbated by microplastics (MPs) exposure in juvenile rats.

Malnutrition-Inflammation Score of Patients with Chronic Kidney Disease from Early Stage to Initiation of Dialysis.

The malnutrition-inflammation score (MIS) is a practical and accessible tool for evaluating protein energy wasting (PEW) in patients on dialysis. However, the severity of PEW at each stage of chronic kidney disease (CKD), especially with late dialysis initiation, is unclear. We evaluated the MIS of 3659 patients with CKD stages 1-5 and the changes in their MIS results at baseline and at the time before dialysis initiation.

Hepatitis and Hepatitis B Virus Reactivation in Everolimus-Treated Solid Tumor Patients: A Focus on HBV-Endemic Areas.

Background: Everolimus is approved for treating breast, renal, and pancreatic neuroendocrine cancers but carries the risk of hepatitis B virus (HBV) reactivation (HBVr) and hepatitis. However, data on HBVr in everolimus-treated patients are limited. This study evaluates the risk of hepatitis and HBVr in cancer patients with current or past HBV infection.

Occupational Therapists' Perspectives on Community Implementation of Interventions Unfamiliar to Older Adults.

Background And Objectives: There is an increasing push for broad implementation of evidence-based interventions (EBIs) targeting older adults. Successful delivery of EBIs in communities requires therapists to adhere to protocols and to be responsive to contextual factors. This study explored the real-world implementation of an EBI, the Multiple-component Cognitive Intervention using Simulated Everyday Tasks (MCI-SET) in Taiwan from therapists' perspectives on fidelity, challenges, and strategies for program delivery.

Habitual tea consumption is associated with a lower prevalence of kidney stone disease in postmenopausal women.

Background: Menopause is associated with an increased risk of kidney stone disease (KSD). However, for postmenopausal women, how to avoid KSD has rarely been studied. The aim of this study was to explore whether drinking tea is associated with a reduction in the prevalence of KSD in postmenopausal women.