Murine Models and Human Cell Line Models to Study Altered Dynamics of Ovarian Follicles in Polycystic Ovary Syndrome.

Polycystic ovary syndrome is one of the most common endocrine disorders in women of reproductive age, characterized by functional and structural alterations of the female reproductive organs. Due to the unknown underlying molecular mechanisms, in vivo murine models and in vitro human cellular models are developed to study the syndrome. These models are used to analyze various aspects of the pathology by replicating the conditions of the syndrome.

Ground Reaction Forces and Joint Moments Predict Metabolic Cost in Physical Performance: Harnessing the Power of Artificial Neural Networks.

Understanding metabolic cost through biomechanical data, including ground reaction forces (GRFs) and joint moments, is vital for health, sports, and rehabilitation. The long stabilization time (2-5 min) of indirect calorimetry poses challenges in prolonged tests. This study investigated using artificial neural networks (ANNs) to predict metabolic costs from the GRF and joint moment time series.

A mutant ASXL1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.

Unlabelled: is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and . CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML), and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing de-repression of silenced elements in heterochromatin.

Uncertainty estimation in diagnosis generation from large language models: next-word probability is not pre-test probability.

Objective: To evaluate large language models (LLMs) for pre-test diagnostic probability estimation and compare their uncertainty estimation performance with a traditional machine learning classifier.

Materials And Methods: We assessed 2 instruction-tuned LLMs, Mistral-7B-Instruct and Llama3-70B-chat-hf, on predicting binary outcomes for Sepsis, Arrhythmia, and Congestive Heart Failure (CHF) using electronic health record (EHR) data from 660 patients. Three uncertainty estimation methods-Verbalized Confidence, Token Logits, and LLM Embedding+XGB-were compared against an eXtreme Gradient Boosting (XGB) classifier trained on raw EHR data.

Elevation of ganglioside degradation pathway drives GM2 and GM3 within amyloid plaques in a transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that accounts for two-thirds of all dementia cases, and age is the strongest risk factor. In addition to the amyloid hypothesis, lipid dysregulation is now recognized as a core component of AD pathology. Gangliosides are a class of membrane lipids of the glycosphingolipid family and are enriched in the central nervous system (CNS).

Reduced White Matter Damage and Lower Neuroinflammatory Potential of Microglia and Macrophages in Hri/Eif2ak1 Mice After Contusive Spinal Cord Injury.

Cellular stressors inhibit general protein synthesis while upregulating stress response transcripts and/or proteins. Phosphorylation of the translation factor eIF2α by one of the several stress-activated kinases is a trigger for such signaling, known as the integrated stress response (ISR). The ISR regulates cell survival and function under stress.

Patient Perspectives of Fertility Following Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy: An Opportunity for Improved Perioperative Counseling.

Introduction: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is increasingly performed in young patients with peritoneal surface malignancies. Important quality of life (QoL) questions arise; however, there is limited research on fertility experiences in young women with carcinomatosis or following CRS/HIPEC.

Methods: Retrospective review of a prospective database evaluating women less than 45 ys who underwent CRS/HIPEC at the University of Pittsburgh Medical Center from January 1998 to 2020.

Efficacy, Indications, and Safety of Intrathecal Baclofen Pump: A Narrative Review.

Purpose Of Review: Baclofen, a muscle relaxant that reduces the release of excitatory neurotransmitters in the pre-synaptic neurons stimulating inhibitory neuronal signals in post-synaptic neurons, has been around for over 5 decades. Baclofen is used primarily for spasticity and since 1982, has had a role as an intrathecal agent. In the present investigation, we review research trends and updates on safety and efficacy of intrathecal baclofen (ITB) pumps.

A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.

is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and (. CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML) and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways, respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing derepression of silenced elements in heterochromatin.

Water, Solute, and Ion Transport in De Novo-Designed Membrane Protein Channels.

Biological organisms engineer peptide sequences to fold into membrane pore proteins capable of performing a wide variety of transport functions. Synthetic de novo-designed membrane pores can mimic this approach to achieve a potentially even larger set of functions. Here we explore water, solute, and ion transport in three de novo designed β-barrel membrane channels in the 5-10 Å pore size range.

Lessons learned on information retrieval in electronic health records: a comparison of embedding models and pooling strategies.

Objectives: Applying large language models (LLMs) to the clinical domain is challenging due to the context-heavy nature of processing medical records. Retrieval-augmented generation (RAG) offers a solution by facilitating reasoning over large text sources. However, there are many parameters to optimize in just the retrieval system alone.

People expect artificial moral advisors to be more utilitarian and distrust utilitarian moral advisors.

As machines powered by artificial intelligence increase in their technological capacities, there is a growing interest in the theoretical and practical idea of artificial moral advisors (AMAs): systems powered by artificial intelligence that are explicitly designed to assist humans in making ethical decisions. Across four pre-registered studies (total N = 2604) we investigated how people perceive and trust artificial moral advisors compared to human advisors. Extending previous work on algorithmic aversion, we show that people have a significant aversion to AMAs (vs humans) giving moral advice, while also showing that this is particularly the case when advisors - human and AI alike - gave advice based on utilitarian principles.

Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic: A Randomized Clinical Trial.

Importance: The psychological morbidity experienced by physicians, advanced practice practitioners (APPs), and nurses from working during the COVID-19 pandemic includes burnout, depression, and posttraumatic stress disorder (PTSD).

Objective: To investigate whether psilocybin therapy could improve symptoms of depression, burnout, and PTSD in US clinicians who developed these symptoms from frontline clinical work during the pandemic.

Design, Setting, And Participants: This double-blind randomized clinical trial enrolled participants from February to December 2022.

A comparison of role-related physical fitness between British Army trainees and trained soldiers.

British Army basic training (BT) and initial trade training (ITT) enable personnel to develop role-related physical capability to perform in-service job-roles. The study aimed to compare physical performance of trainees (completing ITT) and trained soldiers, on a series of gym-based fitness tests and representative military tasks. A total of 316 British Army personnel [68 trainees (63 men: 22 ± 3 years, 71.

Effects of Supervised Exercise Therapy on Muscle Function During Walking in Patients with Peripheral Artery Disease.

Background: Although supervised exercise therapy (SET) is a primary treatment for peripheral artery disease (PAD), the current literature is limited regarding the mechanisms contributing to increased walking distances, including how lower extremity muscle function is altered after SET. This study aimed to investigate the effects of SET on lower extremity muscle function during walking in patients with PAD.

Methods: Twelve patients with PAD participated in a 6-month SET program consisting of three weekly exercise sessions (a total of 72 sessions) and adhered to the American College of Sports Medicine's (ACSM) recommendations.

Efficacy of Inpatient, Evidence-Based Tobacco Use Treatment of Patients With Bladder Cancer After Radical Cystectomy.

Purpose: Despite a 3-fold increase in risks of bladder cancer (BC) among current smokers, smoking cessation therapy for patients undergoing treatment is significantly underutilized. Inpatient admission after surgery provides a teachable moment to pursue tobacco treatment. We conducted a 12-month prospective quality improvement initiative to increase tobacco treatment program (TTP) consultations with BC patients who smoke and underwent radical cystectomy (RC).

Increasing Effective Primary Care Screenings in the U.S. Virgin Islands Department of Health Community Clinic.

In 2019, 1.8 million new cancer cases occurred, and 500,000 cancer deaths were expected in the United States, costing $21 billion. Regular primary care screenings have correlated with early cancer detection, treatment, health promotion, and reduced costs.

Financial Difficulty Over Time in Young Adults With Breast Cancer.

Importance: Young adults aged 18 to 39 years represent the minority of breast cancer diagnoses but are particularly vulnerable to financial hardship. Factors contributing to sustained financial hardship are unknown.

Objectives: To identify financial hardship patterns over time and characterize factors associated with discrete trajectories; it was hypothesized that treatment-related arm morbidity, a key source of expense, would be associated with long-term financial difficulty.

Ligand distances as key predictors of pathogenicity and function in NMDA receptors.

Genetic variants in the genes GRIN1, GRIN2A, GRIN2B, and GRIN2D, which encode subunits of the N-methyl-D-aspartate receptor (NMDAR), have been associated with severe and heterogeneous neurologic and neurodevelopmental disorders, including early onset epilepsy, developmental and epileptic encephalopathy, intellectual disability, and autism spectrum disorders. Missense variants in these genes can result in gain or loss of the NMDAR function, requiring opposite therapeutic treatments. Computational methods that predict pathogenicity and molecular functional effects of missense variants are therefore crucial for therapeutic applications.

Perspectives of Young Women with Breast Cancer: Patient Experiences Indicate Opportunities to Improve Treatment.

In this focus group study of 11 women younger than 45 years of age treated at Memorial Sloan Kettering Cancer Center (New York, NY, USA) between March 2020 and April 2021, patients were asked about their preferences for types of resources, and timing and method of information delivery. Patients expressed interest in personalized medicine, access to integrative health and a holistic approach to treatment, and early consultation for fertility preservation. Their narratives elaborated on how age at diagnosis influences interpersonal relationships and quality of life, and provides direction for interventions to better counsel and support this population.

Yoga as an intervention for stress: a meta-analysis.

The escalating stress epidemic in modern society has raised concerns about its impact on physical and mental health, prompting the need for effective interventions. Yoga, a multifaceted mind-body practice, has gained recognition for its potential in mitigating perceived stress. Our meta-analysis aimed to estimate yoga's impact on lowering perceived stress as measured by the Perceived Stress Scale.