Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden.

Patients with metastatic breast cancer face reduced quality of life and increased mortality rates, necessitating more effective anti-cancer strategies. Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver metastatic breast cancer's response to Fulvestrant (Fulv) treatment. Using in vitro cell lines and in vivo xenograft metastasis mouse models, we examined the molecular mechanisms of combining ER targeting with a ketogenic diet.

Longitudinal Trends in Physical Activity Among Older Adults With and Without HIV in Uganda.

Introduction: Physical Activity (PA) and its links to frailty, quality of life (QoL), and other comorbidities in older Ugandans living with HIV remain under-explored.

Methods: We analyzed data from three annual assessments of older people living with HIV (PLWH) and age- and sex-similar people not living with HIV (PnLWH). We fitted linear generalized estimating equations (GEE) regression models to estimate the correlates of PA, including demographics, frailty, QoL, HIV, and other comorbidities.

Stepwise order in protein complex assembly: approaches and emerging themes.

Protein-based nanomachines drive every cellular process. An explosion of high-resolution structures of multiprotein complexes has improved our understanding of what these machines look like and how they work, but we still know relatively little about how they assemble in living cells. For example, it has only recently been appreciated that many complexes assemble co-translationally, with at least one subunit still undergoing active translation while already interacting with other subunits.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.

The Combined Effect of Multisensory Stimulation and Therapist Support on Physical and Mental Health of Older Adults Living in Nursing Homes: Pilot Randomized Controlled Trial.

Background: Increasing life expectancy has led to a rise in nursing home admissions, a context in which older adults often experience chronic physical and mental health conditions, chronic pain, and reduced well-being. Nonpharmacological approaches are especially important for managing older adults' chronic pain, mental health conditions (such as anxiety and depression), and overall well-being, including sensory stimulation (SS) and therapist support (TS). However, the combined effects of SS and TS have not been investigated.

Phase I Dose Volume Escalation of Rectally Administered PC-1005 to Assess Safety, Pharmacokinetics, and Antiviral Pharmacodynamics as a Multipurpose Prevention Technology (MTN-037).

Background: On demand, topical PrEP is desired by those preferring episodic, nonsystemic PrEP. PC-1005 gel (MIV-150, zinc, and carrageenan) exhibits in vitro antiviral HIV-1, human papillomavirus (HPV), and herpes simplex virus type 2 (HSV-2) activity, attractive for a multipurpose prevention technology candidate. We evaluated the safety, pharmacokinetics, and antiviral effect of rectally applied PC-1005.

Development and validation of a pragmatic measure of cocreation in research engagement: a study protocol.

Introduction: Cocreation, a collaborative process of key interested partners working alongside researchers, is fundamental to community-engaged research. However, the field of community-engaged research is currently grappling with a significant gap: the lack of a pragmatic and validated measure to assess the quality of this process. This protocol addresses this significant gap by developing and testing a pragmatic cocreation measure with diverse community and research partners involved in participatory health-related research.

Dry eye post-cataract surgery: a systematic review and meta-analysis.

Significance: Cataract surgery is one of the most performed surgical procedures worldwide. As a potential complication following cataract surgery, dry eye has the potential to impact visual outcomes, lower patient satisfaction, and be detrimental to quality of life.

Purpose: To evaluate the effect of cataract surgery on dry eye outcomes postoperatively.

Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms.

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms.

Evaluation of a Program Designed to Support Implementation of Prescribing Medication for Treatment of Opioid Use Disorder in Primary Care Practices.

Purpose: Offering medication for opioid use disorder (MOUD) in primary care can increase access to effective opioid use disorder treatment and help address the US opioid crisis. We describe a primary care office-based opioid treatment program and addiction consultation service model designed to support small, rural clinics to increase their capacity for MOUD.

Methods: This is an evaluation of an intervention to increase clinic capacity to offer MOUD.

CD93 blockade promotes effector T-cell infiltration and facilitates adoptive cell therapy in solid tumors.

Background: Adaptive cellular therapy (ACT), particularly chimeric antigen receptor (CAR)-T cell therapy, has been successful in the treatment of hemopoietic malignancies. However, poor trafficking of administered effector T cells to the tumor poses a great hurdle for this otherwise powerful therapeutic approach in solid cancers. Our previous study revealed that targeting CD93 normalizes tumor vascular functions to improve immune checkpoint blockade therapy.

Economic Impact of the Apoyo con Cariño Intervention: Improving Palliative Care for Hispanics with Serious Illness.

Specialty palliative care has been associated with cost savings at the end of life, while patient navigators have been independently associated with cost savings due to screening and treatment early in the course of disease. Evidence is limited regarding patient navigators and cost savings at the end of life. To determine the cost-effectiveness of a lay patient navigator intervention in improving palliative care outcomes for Hispanic persons with serious noncancer illness.

Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited.

Objective: To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms (z score ≥2.

Technology in the Trenches: The Impact of evolving technologies on Combat Mental Health.

Purpose Of Review: Medicine and specifically mental health have been affected by emerging technologies advancing mental health treatment while at the same time bringing new challenges and stressors to the battlefield, military systems, and the warfighter.

Recent Findings: This article reviews the evolving positive and negative impacts of technology on combat mental health and treatment. A history of technology and military mental health concerns and services is followed by an overview of present benefits and risks.

Are women really (not) more talkative than men? A registered report of binary gender similarities/differences in daily word use.

Women are widely assumed to be more talkative than men. Challenging this assumption, Mehl et al. (2007) provided empirical evidence that men and women do not differ significantly in their daily word use, speaking about 16,000 words per day (WPD) each.

Mechanistic Target of Rapamycin Signaling Activity in the Human Placenta Across Gestation and in Maternal Obesity.

The mechanistic target of rapamycin (mTOR) system is vital to placental development, formation, and function. Alterations in this system in the placenta have been associated with altered fetal growth. However, changes in placental mTOR signaling across gestation are poorly understood.

Scutellarein Inhibits Osteosarcoma Growth by Targeting the TLR4/TRAF6/NF-κB Pathway.

Purpose: Osteosarcoma (OS) is the most common malignant tumor associated with poor patient outcomes and a limited availability of therapeutic agents. Scutellarein (SCU) is a monomeric flavone bioactive compound with potent anti-cancer activity. However, the effects and mechanisms of SCU on the growth of OS remain unknown.

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.

Associations of maternal per- and polyfluoroalkyl substance plasma concentrations during pregnancy with offspring polycystic ovary syndrome and related characteristics in Project Viva.

Background: Per- and polyfluoroalkyl substances (PFAS) may impact ovarian folliculogenesis and steroidogenesis, but whether prenatal exposure may impact offspring reproductive health is unknown. This study examines the extent to which maternal PFAS plasma concentrations during pregnancy are associated with polycystic ovary syndrome (PCOS) and related characteristics in female offspring.

Methods: We studied 322 mother-daughter pairs in Project Viva, a Boston-area longitudinal pre-birth cohort enrolled 1999-2002.

Diurnal fluctuations of subthalamic nucleus local field potentials follow naturalistic sleep-wake behavior in Parkinson's disease.

Study Objectives: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) may improve sleep dysfunction, a common non-motor symptom of Parkinson disease (PD). Improvement in motor symptoms correlates with DBS-suppressed local field potential (LFP) activity, particularly in the beta frequency (13 - 30 Hz). Although well-characterized in the short term, little is known about the innate progression of these oscillations across the sleep-wake cycle.

The Society of Thoracic Surgeons (STS) Clinical Practice Guideline on Surgical Management of Oligometastatic Non-small Cell Lung Cancer.

Background: The use of local consolidative therapy (LCT) in patients with oligometastatic non-small cell lung cancer (NSCLC) is rapidly evolving, with a preponderance of data supporting the benefits of such therapeutic approaches incorporating pulmonary resection for appropriately selected candidates. However, practices vary widely institutionally and regionally, and evidence-based guidelines are lacking.

Methods: The Society of Thoracic Surgeons assembled a panel of thoracic surgical oncologists to evaluate and synthesize the available evidence regarding the role of pulmonary resection as LCT.

NKX2.2 and KLF4 cooperate to regulate α-cell identity.

Transcription factors (TFs) are indispensable for maintaining cell identity through regulating cell-specific gene expression. Distinct cell identities derived from a common progenitor are frequently perpetuated by shared TFs, yet the mechanisms that enable these TFs to regulate cell-specific targets are poorly characterized. We report that the TF NKX2.