Exploring the relationship between the androgen receptor and structural configuration of benzophenones: a combination of computational analysis and laboratory models.

This study explored the interactions between benzophenones (BPs) and androgen receptors (AR) using computational and experimental approaches. BPs are potential endocrine disruptors that are commonly found in cosmetics, such as sunscreen. Molecular docking and molecular mechanics with generalized Born and surface area continuum solvation calculations revealed that dihydroxylation form of BP-1, BP-2 had higher binding affinities to AR compared with BP-1, BP-3.

Trio-Based Whole-Genome Sequencing for Critically Ill Pediatric Patients in Korea.

This study aimed to implement whole-genome sequencing using an automated pipeline for critically ill pediatric patients within a real-world health care system. Twenty patients under 36 months of age, admitted to the neonatal or pediatric intensive care unit or suspected of having rapidly progressive genetic disorders, were enrolled. Trio-based whole-genome sequencing was performed using an optimized processing pipeline, which automatically performed mapping, variant calling, annotation, and in silico pathogenicity assessment.

Modulating phosphatase DUSP22 with BML-260 ameliorates skeletal muscle wasting via Akt independent JNK-FOXO3a repression.

Skeletal muscle wasting results from numerous conditions, such as sarcopenia, glucocorticoid therapy or intensive care. It prevents independent living in the elderly, predisposes to secondary diseases, and ultimately reduces lifespan. There is no approved drug therapy and the major causative mechanisms are not fully understood.

Smart insole-based abnormal gait identification: Deep sequential networks and feature ablation study.

Objective: Gait analysis plays a pivotal role in evaluating walking abilities, with recent advancements in digital health stressing the importance of efficient data collection methods. This study aims to classify nine gait types including one normal and eight abnormal gaits, using sequential network-based models and diverse feature combinations obtained from insole sensors.

Methods: The dataset was collected using insole sensors from subjects performing 15 m walking with designated gait types.

Regulation of Ferroptosis in Cancer and Immune Cells.

Ferroptosis, an iron-dependent form of regulated cell death, is driven by lipid peroxidation and shaped by metabolic and antioxidant pathways. In immune cells, ferroptosis susceptibility varies by cell types, lipid composition, and metabolic demands, influencing immune responses in cancer, infections, and autoimmune diseases. Therapeutically, targeting ferroptosis holds promise in cancer immunotherapy by enhancing antitumor immunity or inhibiting immunosuppressive cells.

Classification of Abnormal Gaits with Machine Learning Algorithms using Sensor-Inherited Insoles.

The digital health industry's interest in gait analysis has driven research into sensor-enabled insoles for practical, everyday gait monitoring. Traditional methods, such as 3D motion capture systems, are costly and time-consuming. To address this, we propose an efficient method to evaluate gait performance.

Gait impairment associated with neuroimaging biomarkers in Alzheimer's disease.

Research links gait impairment in Alzheimer's disease (AD) to cognitive abnormalities, brain atrophy, or amyloid-β (Aβ) deposition, with the exact cause unclear. This study investigated the relationship between gait, neuroimaging biomarkers, and cognition across the AD spectrum. We recruited 48 AD dementia patients, 27 with prodromal AD, and 41 cognitively unimpaired individuals, analyzing associations among gait parameters, cognitive scores, Aβ deposition, and cortical atrophy.

sp. nov. and sp. nov., two bacteria isolated from marine sediment in the East China Sea.

Two Gram-stain-negative, curved-rod-shaped, non-motile and aerobic bacteria W6 and I13 were isolated from marine sediment samples collected from Meishan Island located in the East China Sea. Catalase and oxidase activities and hydrolysis of Tween 40, 60 and 80 were positive for both strains, while nitrate reduction, indole production, methyl red reaction and HS production were negative. Phylogenetic analyses based on 16S rRNA and genome sequences revealed that strains W6 and I13 formed distinct phylogenetic lineages within the genera and , respectively.

Identifying Parkinson's disease and its stages using static standing balance.

The current assessment of Parkinson's disease (PD) relies on dynamic motor tasks, limiting accessibility. This study aimed to propose an innovative approach to identifying PD and its stages using static standing balance and machine learning. A total of 210 participants were recruited, including a control group and five PD groups categorized by stage.

Evaluation of Vancomycin Dose Needed to Achieve 24-Hour Area Under the Concentration-Time Curve to Minimum Inhibitory Concentration Ratio Greater Than or Equal to 400 Using Pharmacometric Approaches in Pediatric Intensive Care Patients.

Objectives: To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400.

Design: Prospective population pharmacokinetic study of vancomycin.

Setting: Critically ill patients in quaternary care PICUs.

PUM1-TRAF3 fusion protein activates non-canonical NF-κB signaling via rescued NIK in biliary tract cancer.

Discovery and verification of diagnostic or therapeutic biomarkers for biliary tract cancer (BTC) is challenging owing to the low prevalence of the disease. Here, we identified and investigated the clinical impact of a fusion gene, Pumilio1-tumor necrosis factor receptor-associated factor 3 (PUM1-TRAF3), caused by 1;14 chromosomal translocation in BTC. PUM1-TRAF3 was initially identified in the RNA-sequencing of five BTC surgical tissues and confirmed by fluorescence in situ hybridization.

Pharmacokinetics of Briquilimab as a Conditioning Agent for Hematopoietic Stem Cell Transplantation in Patients With Severe Combined Immunodeficiency, Myelodysplastic Syndrome, or Acute Myeloid Leukemia.

For successful engraftment of donor hematopoietic stem cells (HSC), conditioning with chemotherapy and/or radiation prior to hematopoietic cell transplantation (HCT) has been required to open marrow niche space and minimize the risk of immune rejection. Briquilimab, a humanized IgG1 monoclonal antibody that blocks the interaction between the c-Kit receptor and stem cell factor on various C-Kit expressing tissues including HSC, is a potential nonmyeloablative conditioning agent in clinical development for patients with severe combined immunodeficiency (SCID), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). This study aimed to characterize pharmacokinetics (PK) and develop a population PK model of briquilimab after single intravenous infusions of 4 different doses in patients with SCID, MDS, or AML receiving HCT.

Pharmacokinetics of Human Plasma-Derived Antithrombin in Pediatric Patients Supported on Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) support of critically ill pediatric patients is associated with increased risk of thromboembolic events, and unfractionated heparin is used commonly for anticoagulation. Given reports of acquired antithrombin (AT) deficiency in this patient population and associated concern for heparin resistance, AT activity measurement and off-label AT replacement have become common in pediatric ECMO centers despite limited optimal dosing regimens. We conducted a retrospective cohort study of pediatric ECMO patients (0 to <18 years) at a single academic center to characterize the pharmacokinetics (PK) of human plasma-derived AT.

Confirmation of the steroid hormone receptor-mediated endocrine disrupting potential of fenvalerate following the Organization for Economic Cooperation and Development test guidelines, and its estrogen receptor α-dependent effects on lipid accumulation.

In this study, we focused on confirming the steroid hormone receptor-mediated endocrine-disrupting potential of the pyrethroid insecticide fenvalerate and unraveling the underlying mechanisms. Therefore, we assessed estrogen receptor-α (ERα)- and androgen receptor (AR)-mediated responses in vitro using a hormone response element-dependent transcription activation assay with a luciferase reporter following the Organization for Economic Cooperation and Development (OECD) test guidelines. We observed that fenvalerate acted as estrogen by inducing the translocation of cytosolic ERα to the nucleus via ERα dimerization, whereas it exhibited no AR-mediated androgen response element-dependent luciferase activity.

Daily vitality fluctuations in older adults with depressive symptoms: A multilevel location-scale model.

Background: Examining the daily experiences of older adults with depression facilitates the development and application of personalized effective treatments for them. In previous clinical research on depression, traditional mean-based approaches have mainly been employed. However, the within-person residual variance as a random effect provides greater insight into the heterogeneity of daily experiences among geriatric samples.

Transgelin-2, a novel cancer stem cell-related biomarker, is a diagnostic and therapeutic target for biliary tract cancer.

Background: Biliary tract cancer (BTC) is a relatively rare but aggressive gastrointestinal cancer with a high mortality rate. Cancer stem cell (CSC) populations play crucial roles in tumor biology and are responsible for the low response to anti-cancer treatment and the high recurrence rate. This study investigated the role of Transgelin-2 (TAGLN2), overexpressed in CSC in BTC cells, and analyzed its expression in patient tissues and serum to identify potential new targets for BTC.

Mechanistic insight into human androgen receptor-mediated endocrine disrupting potential of cyclic depsipeptide mycotoxin, beauvericin, and influencing environmental factors for its biosynthesis in Fusarium oxysporum KFCC 11363P on rice cereal.

In current study, Fusarium mycotoxin, beauvericin (BEA), has endocrine disrupting potential through suppressing the exogenous androgen receptor (AR)-mediated transcriptional activation. BEA was classified as an AR antagonist, with IC and IC values indicating that it suppressed AR dimerization in the cytosol. BEA suppress the translocation of cytosolic activated ARs to the nucleus via exogenous androgens.

Stimulation of estrogen receptor-alpha by hydroxyanilide fungicide, fenhexamid promotes lipid accumulation in 3 T3-L1 adipocyte.

Fenhexamid are fungicides that act against plant pathogens by inhibiting sterol biosynthesis. Nonetheless, it can trigger endocrine disruption and promote breast cancer cell growth. In a recent study, we investigated the mechanism underlying the lipid accumulation induced by fenhexamid hydroxyanilide fungicides in 3 T3-L1 adipocytes.

sEMG-based Sarcopenia risk classification using empirical mode decomposition and machine learning algorithms.

Early detection of the risk of sarcopenia at younger ages is crucial for implementing preventive strategies, fostering healthy muscle development, and minimizing the negative impact of sarcopenia on health and aging. In this study, we propose a novel sarcopenia risk detection technique that combines surface electromyography (sEMG) signals and empirical mode decomposition (EMD) with machine learning algorithms. First, we recorded and preprocessed sEMG data from both healthy and at-risk individuals during various physical activities, including normal walking, fast walking, performing a standard squat, and performing a wide squat.

Deciphering the mechanisms and interactions of the endocrine disruptor bisphenol A and its analogs with the androgen receptor.

Bisphenol A (BPA) and its various forms used as BPA alternatives in industries are recognized toxic compounds and antiandrogenic endocrine disruptors. These chemicals are widespread in the environment and frequently detected in biological samples. Concerns exist about their impact on hormones, disrupting natural biological processes in humans, together with their negative impacts on the environment and biotic life.

Beauvericin, produced by Fusarium oxysporum inhibits bisphenol A-induced proliferation of human breast cancer cell line by regulating ERα/p38 pathway.

Beauvericin (BEA) is a cyclic depsipeptide secondary metabolite of Fusarium species. It causes chemical hazards in food products and exists in an environment containing soil and various food types. On the other hand, the purified BEA has various biological activities and is regarded as a potential candidate for pharmaceutical research.

Integrated drug response prediction models pinpoint repurposed drugs with effectiveness against rhabdomyosarcoma.

Targeted therapies for inhibiting the growth of cancer cells or inducing apoptosis are urgently needed for effective rhabdomyosarcoma (RMS) treatment. However, identifying cancer-targeting compounds with few side effects, among the many potential compounds, is expensive and time-consuming. A computational approach to reduce the number of potential candidate drugs can facilitate the discovery of attractive lead compounds.

Differential DNA methylation and metabolite profiling of Atlantic killifish (Fundulus heteroclitus) from the New Bedford Harbor Superfund site.

Atlantic killifish (Fundulus heteroclitus) is a valuable model in evolutionary toxicology to study how the interactions between genetic and environmental factors serve the adaptive ability of organisms to resist chemical pollution. Killifish populations inhabiting environmental toxicant-contaminated New Bedford Harbor (NBH) show phenotypes tolerant to polychlorinated biphenyls (PCBs) and differences at the transcriptional and genomic levels. However, limited research has explored epigenetic alterations and metabolic effects in NBH killifish.

Image-based Gait Spatiotemporal Parameters Estimation using a Single Camera and CNN-Transformer Hybrid Network.

Vision-based gait analysis can play an important role in the remote and continuous monitoring of the elderly's health conditions. However, most vision-based approaches compute gait spatiotemporal parameters using human pose information and provide average parameters. This study aimed to propose a straightforward method for stride-by-stride gait spatiotemporal parameters estimation.