The PH domain in the ArfGAP ASAP1 drives catalytic activation through an unprecedented allosteric mechanism.

ASAP1 is a multidomain Arf GTPase-activating protein (ArfGAP) that catalyzes GTP hydrolysis on the small GTPase Arf1 and is implicated in cancer progression. The PH domain of ASAP1 enhances its activity greater than 7 orders of magnitude but the underlying mechanisms remain poorly understood. Here, we combined Nuclear Magnetic Resonance (NMR), Molecular Dynamic (MD) simulations and mathematical modeling of functional data to build a comprehensive structural-mechanistic model of the complex of Arf1 and the ASAP1 PH domain on a membrane surface.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

UPJE: Most pharmacy law educators have heard of it, but support remains divided.

Background: Most states require pharmacists to successfully pass the Multistate Pharmacy Jurisprudence Examination (MPJE) required by the National Association of Boards of Pharmacy (NABP) to obtain licensure as a pharmacist, though pass rates for the MPJE have declined in recent years. Meanwhile, NABP is pursing efforts to standardize the exam with the emergent Uniform Pharmacy Jurisprudence Examination (UPJE).

Objective: This study aimed to describe the current thinking of pharmacy law educators across the US on the UPJE.

Assessing the benefit-risk profile of newer glucose-lowering drugs: A systematic review and network meta-analysis of randomized outcome trials.

Aim: To comprehensively evaluate the benefits and risks of glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase 4 inhibitors (DPP4i), and sodium-glucose cotransporter 2 inhibitors (SGLT2i).

Materials And Methods: A systematic search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 2023 to identify randomized cardiovascular and kidney outcome trials that enrolled adults with type 2 diabetes, heart failure, or chronic kidney disease and compared DPP4i, GLP-1RAs, or SGLT2i to placebo. Twenty-one outcomes (e.

Relationship Between 1,5 Anhydroglucitol, Glycemia, and Breastfeeding During Pregnancy and Postpartum: A Pilot Study.

Background: Assessments for hyperglycemia are vital to pregnancy and postpartum (PP) care, but gold-standard oral glucose tolerance tests (OGTTs) are burdensome. We examined changes in 1,5 anhydroglucitol (1,5AG) levels during gestation and PP and assessed for associations with other measures of glycemia.

Study Design: Pregnant participants (n = 50) in the Study of Pregnancy Regulation of Insulin and Glucose cohort underwent OGTTs at a mean of 13 weeks ([visit 1 (V1)] and 26 weeks [visit 2 (V2)] of gestation and PP.

RAD51 recruitment but not replication fork stability associates with PARP inhibitor response in ovarian cancer patient-derived xenograft models.

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are currently used to treat mutant cancers. Although PARPi sensitivity has been attributed to homologous recombination (HR) defects, other roles of HR factors have also been linked to response to PARPi, including replication fork protection. In this study, we investigated PARPi sensitivity in ovarian cancer patient-derived xenograft (PDX) models in relation to HR proficiency and replication fork protection.

Diversity of bacteria within the human gut and its contribution to the functional unity of holobionts.

The composition of bacteria in the human colon has been a subject of interest since the beginning of microbiology. With the development of methods for culturing strict anaerobic bacteria under multiple culture conditions, it was shown the gut contained more than 400 bacterial species and different people harbor different abundant species. The term "gut microbiome" in this review refers to bacteria studied in stool samples.

Case report: VEXAS syndrome with excellent response to treatment with azacitidine.

Vacuoles, E1 enzyme, X-linked, auto inflammatory, somatic (VEXAS) syndrome is an inflammatory disorder caused by somatic UBA1 variants and is characterized by late-onset systemic autoimmune inflammation and blood abnormalities. Glucocorticoids ameliorate symptoms effectively. However, other treatment options have limited efficacy and a transient effect.

Recommendations for Clinicians, Technologists, and Healthcare Organizations on the Use of Generative Artificial Intelligence in Medicine: A Position Statement from the Society of General Internal Medicine.

Generative artificial intelligence (generative AI) is a new technology with potentially broad applications across important domains of healthcare, but serious questions remain about how to balance the promise of generative AI against unintended consequences from adoption of these tools. In this position statement, we provide recommendations on behalf of the Society of General Internal Medicine on how clinicians, technologists, and healthcare organizations can approach the use of these tools. We focus on three major domains of medical practice where clinicians and technology experts believe generative AI will have substantial immediate and long-term impacts: clinical decision-making, health systems optimization, and the patient-physician relationship.

Intensified alkylating chemotherapy for patients with oligometastatic breast cancer harboring homologous recombination deficiency: Primary outcomes from the randomized phase III OLIGO study.

Background: Oligometastatic breast cancer (OMBC) is a clinical entity with a prospect of long-term survival, but uncertainty remains on its optimal treatment. We studied whether intensified alkylating chemotherapy (IACT) improves long-term outcome compared to conventional-dose chemotherapy (CDCT) as part of a multimodality approach for patients with OMBC harboring homologous recombination deficiency (HRD).

Patients And Methods: Eligible patients had HER2-negative OMBC, harboring HRD, with ≤ 3 distant metastases, pathologic proof of distant disease and a favorable response to three cycles CDCT.

Auto-Abs neutralizing type I IFNs in patients with severe Powassan, Usutu, or Ross River virus disease.

Arboviral diseases are a growing global health concern. Pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) can underlie encephalitis due to West Nile virus (WNV) (∼40% of patients) and tick-borne encephalitis (TBE, due to TBE virus [TBEV]) (∼10%). We report here that these auto-Abs can also underlie severe forms of rarer arboviral infections.

Wastewater Surveillance for Poliovirus in Selected Jurisdictions, United States, 2022-2023.

Wastewater testing can inform public health action as a component of polio outbreak response. During 2022-2023, a total of 7 US jurisdictions (5 states and 2 cities) participated in prospective or retrospective testing of wastewater for poliovirus after a paralytic polio case was identified in New York state. Two distinct vaccine-derived poliovirus type 2 viruses were detected in wastewater from New York state and New York City during 2022, representing 2 separate importation events.

Design and development of a machine-learning-driven opioid overdose risk prediction tool integrated in electronic health records in primary care settings.

Background: Integrating advanced machine-learning (ML) algorithms into clinical practice is challenging and requires interdisciplinary collaboration to develop transparent, interpretable, and ethically sound clinical decision support (CDS) tools. We aimed to design a ML-driven CDS tool to predict opioid overdose risk and gather feedback for its integration into the University of Florida Health (UFHealth) electronic health record (EHR) system.

Methods: We used user-centered design methods to integrate the ML algorithm into the EHR system.

Impact of TearCare on Reading Speed in Patients with Dry Eye Disease.

Purpose: To evaluate the impact of TearCare (TC) treatment on clinical, quality of life, and functional visual outcome metrics in patients with dry eye disease (DED) and meibomian gland disease (MGD).

Methods: This is a prospective, single-center clinical trial. Adults with MGD and a DED diagnosis and tear break-up time (TBUT) <10 seconds were included.

Phase transitions in random circuit sampling.

Undesired coupling to the surrounding environment destroys long-range correlations in quantum processors and hinders coherent evolution in the nominally available computational space. This noise is an outstanding challenge when leveraging the computation power of near-term quantum processors. It has been shown that benchmarking random circuit sampling with cross-entropy benchmarking can provide an estimate of the effective size of the Hilbert space coherently available.

Update on Preeclampsia and Hypertensive Disorders of Pregnancy.

There have been recent advances in the prevention, diagnosis, and management of hypertensive disorders of pregnancy which complicate approximately 16% of pregnancies in the United States. Initiation of low-dose aspirin by 16 weeks' gestation reduces preeclampsia in high-risk women. The Food and Drug Administration approved the use of the soluble fms-like tyrosine kinase 1/placental growth factor ratio for the short-term prediction of preeclampsia.

Impact of COVID-19 on work loss in the United States- A retrospective database analysis.

Objectives: This study investigates the utilization of work absence benefits among United States (US) employees diagnosed with COVID-19, examining frequency, duration, cost, and types of work loss benefits used.

Methods: This retrospective analysis of the Workpartners Research Reference Database (RRDb) included employees eligible for short- and long-term disability (STD and LTD employer-sponsored benefits, respectively), and other paid work absence benefits from 2018 to 2022. Workpartners RRDb includes over 3.