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Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) reduces bone mineral density in HIV-uninfected men who have sex with men (MSM). We hypothesized that PrEP with TDF-FTC would increase bone turnover markers (BTMs) at week 24 and that vitamin D supplementation from weeks 24 to 48 would blunt this increase. Participants were from a cohort of 398 MSM and transgender women who received daily TDF-FTC for PrEP. At week 24, a prospective intervention group initiated vitamin D3 4,000 IU daily. Concurrent controls were selected from the cohort who took ≤400 IU/day of vitamin D3 matched by age, race, and body mass index. The primary endpoint was the change in procollagen-I N-terminal propeptide (P1NP) from weeks 24 to 48. Paired t-tests were used to compare changes in BTMs between intervention and controls. Among 48 intervention-control pairs, median age was 33 years. At baseline, 68.9% of the intervention group and 77.3% of controls were vitamin D sufficient (≥20 ng/mL, p = .94). P1NP, C-telopeptide, parathyroid hormone (PTH), and 25-OH vitamin D3 did not increase significantly at week 24. P1NP fell by a mean ± SD of -27.6 ± 49.9 pg/mL from weeks 24 to 48 with vitamin D and -2.5 ± 40.2 pg/mL in controls (p = .01). There were no significant between-group differences in the weeks 24-48 change in C-telopeptide, PTH, or 25-OH vitamin D3. Vitamin D3 supplementation with 4,000 IU/day resulted in a significant reduction in the BTM P1NP compared with controls, suggesting that this intervention has potential to improve bone health during PrEP.

Introduction: Acute lymphoblastic leukaemia (ALL) is the most common type of childhood leukaemia with effective chemotherapeutic treatment. However, obesity has been associated with higher ALL chemoresistance rates and lower event‐free survival rates. The molecular mechanism of how obesity promotes chemotherapy resistance is not well delineated. Objectives: This study evaluated the effect of adipocyte maturation on sequestration and metabolism of chemotherapeutic drug daunorubicin (DNR). Methods: Using targeted LC‐MS/MS multi‐analyte assay, DNR sequestration and metabolism were studied in human preadipocyte and adipocyte cell lines, where expressions of DNR‐metabolizing enzymes aldo‐keto reductases (AKR) and carbonyl reductases (CBR) were also evaluated. In addition, to identify the most DNR‐metabolizing AKR/CBR isoforms, recombinant human AKR and CBR enzymes were subject to DNR metabolism. The results were further validated by AKR‐, CBR‐specific inhibitors. Results: This report shows that adipocyte maturation upregulates expressions of AKR and CBR enzymes (by 4‐ to 60‐ folds, p <.05), which is positively associated with enhanced sequestration and metabolism of DNR in adipocytes compared to preadipocytes (by ~30%, p <.05). In particular, adipocyte maturation upregulates AKR1C3 and CBR1, which are the predominate metabolic enzyme isoforms responsible for DNR biotransformation to its metabolites. Conclusion: Fat is an expandable tissue that can sequester and detoxify DNR when stimulated by obesity, likely through the upregulation of DNR‐metabolizing enzymes AKR1C3 and CBR1. Our data partially explains why obese ALL patients may be more likely to become chemoresistant towards DNR, and provides evidence for potential clinical investigation targeting obesity to reduce DNR chemoresistance. [ABSTRACT FROM AUTHOR]

Purpose: This study explores buyers' online omnichannel transaction experience, focusing on integrating livestreaming commerce and online store channels. It shifts the spotlight from the predominant emphasis on online and offline channel integration to the online-only omnichannel environment. Design/methodology/approach: Grounded in social cognitive theory, this study adopts a multi-method approach, integrating structural equation modeling (PLS-SEM) and fuzzy set qualitative comparative analysis (fsQCA) to capture individual and complex interactions among factors. Findings: The study finds that internet usage significantly enhances online omnichannel experience by strengthening the positive effects of factors. While PLS-SEM results assert that channel integration quality positively impacts online omnichannel experience, fsQCA results indicate improved online omnichannel experience can be achieved in configurations where channel integration quality is absent. Research implications: The study introduces a unique conceptualization of online omnichannel, revealing symmetric causal mechanisms of online omnichannel experience and improving the findings with asymmetric mechanisms, highlighting new insights, such as achieving higher experience without extensive shopping innovation or channel integration quality. Practical implications: This study can guide practitioners in understanding the configuration of causal elements that enhance buyers' omnichannel transaction experience through integrated online channels. Originality: This research employs symmetric and asymmetric approaches to investigate transaction experience in an omnichannel setting, whereas the conceptualization of omnichannel emphasizes the integration of online-only channels. [ABSTRACT FROM AUTHOR]

Optimizing sustainability among smallholder farms poses challenges due to inherent trade‐offs. In the study of organic and conventional cocoa smallholder farming in Ghana, 398 farms are assessed using the Food and Agriculture Organsation of the United Nations (FAO) Sustainability Assessment of Food and Agriculture systems (SAFA) Guidelines and Sustainability Monitoring and Assessment Routine (SMART)‐Farm Tool. Organic farming exhibited synergies in environmental aspects (e.g., soil quality, energy efficiency) and between biodiversity conservation and risk management. Conventional farming showed potential vulnerabilities, including trade‐offs with long‐range investments (e.g., chemical inputs) and species diversity. Both systems demand tailored approaches for short‐term economic and environmental sustainability, aligning with community‐wide long‐term goals. To mitigate trade‐offs in conventional farming, smallholders should adopt practices like material reuse, recycling, and recovery within their operations. [ABSTRACT FROM AUTHOR]

Background: Polyvinyl chloride (PVC) gloves are recommended as a safe alternative for patients with rubber accelerator allergy. However, allergic contact dermatitis to other chemicals in PVC gloves has been reported. Objective: To analyze single-use PVC medical examination gloves in the United States for the presence of potential contact allergens. Methods: Using liquid chromatography-mass spectrometry, 20 unique PVC gloves were analyzed in triplicate for 6 chemicals: benzisothiazolinone, bisphenol A, mono(2-ethylhexyl) maleate, tricresyl phosphate, triphenyl phosphate, and triphenyl phosphite. Results: All 20 PVC gloves contained detectable quantities of benzisothiazolinone (range, 0.001-1.48 parts per million [ppm]), bisphenol A (0.01-0.11 ppm), triphenyl phosphate (0.01-2.11 ppm), and triphenyl phosphite (0.001-0.22 ppm). Eighteen (90%) gloves contained mono(2-ethylhexyl) maleate (0.001-0.14 ppm) and 3 (15%) contained tricresyl phosphate (0.001-0.002 ppm). Conclusions: Known allergens were present in all 20 PVC gloves. However, the detected levels were mostly low and their relationship with sensitization and elicitation thresholds requires further study. [ABSTRACT FROM AUTHOR]

This study employs a multimethod approach to examine the factors motivating consumers to interact with brands through live‐streaming platforms and how they affect their hedonic well‐being. The result indicates that exclusively relying on the net effects of the motivating factors could be misleading. It presents an insight into how a mediation effect (psychological engagement) affects the interdependence of the independent variables in achieving hedonic well‐being. Although the structural equation modeling results highlight the significant mediating impact of psychological engagement, the fuzzy‐set qualitative comparative analysis shows that psychological engagement is only a core condition in one configuration (out of the three configurations). That is when two motivational factors (brand awareness and real‐time customer service) act as a substitute, and the others (convenience and consumer–brand relationship quality) are present. Therefore, psychological engagement is indifferent when all motivational factors are present. This study, through the application of a multimethod approach, shows that motivational factors for using live‐streaming are only necessary for escalating consumer well‐being but not sufficient in themselves. [ABSTRACT FROM AUTHOR]

Background: Cellular senescence is a hallmark of aging and has been implicated in several neurodegenerative diseases including Alzheimer's disease (AD). Senescence cells undergo changes in gene expression and metabolism and can exhibit a so‐called "senescence‐associated secretory phenotype" (SASP) characterized by increased secretion of pro‐inflammatory molecules and factors which can damage nearby cells, contributing to AD pathology progression. Method: In this study, we determined mechanisms of cellular senescence using human postmortem brain samples, cellular models, and APOE4 animal models. Bulk (n = 632) and single‐cell nuclei transcriptomic profiling (n = 427) of the human dorsolateral prefrontal cortex (DLPFC) from the Religious Order Study/Memory Aging Project (ROSMAP). Lipidomic profiling was performed on a subset of 200 brains from the midfrontal cortex of ROS. Result: Our findings revealed upregulation of cellular senescence signatures in postmortem AD brain tissues across different cell types in comparison with controls. We identified a strong correlation between SASP and arachidonic acid (AA) metabolism (P<0.001) in bulk RNA. In single cell nuclei transcriptomics, AA Activation was strongly correlated with P2RY12 (homeostatic) microglia (P<0.0001), and was associated with worse performance on all cognitive domains (p<0.001) and AD neuropathology (P<0.001) as shown in the figure. Lipidomic analysis of postmortem brain tissues confirmed activation of AA derived eicosanoids. Pathway analysis implicated the activation of calcium dependent phospholipase A2 (cPLA2). Inhibiting cPLA2 by treatment with ASB14780 reduced senescence‐associated eicosanoids in APOE4 mouse models. Conclusion: This work implicates the sustained activation of homeostatic microglia as an underlying mechanism of cellular senescence in the AD brain. [ABSTRACT FROM AUTHOR]