Identification of asporin as a HER3 ligand exposes a therapeutic vulnerability in prostate cancer.

Cancer-associated fibroblasts (CAFs) are part of the tumor microenvironment (TME) that enable cancer cells to establish metastases, but the mechanisms of these interactions are not fully known. Herein, we identified a paracrine mechanism in which CAF-secreted asporin (ASPN) activated ErbB signaling and subsequent migration of adjacent prostate cancer cells. Our data support that ASPN bound directly to the ligand binding domain of human epidermal growth factor 3 (HER3) and induced HER2/HER3 heterodimerization and activation of the PI3K, MAPK, and calcium pathways.

Improving Residents' Comfort with Salpingectomy at Cesarean Delivery Through Surgical Simulation.

Introduction: To study obstetric and gynecologic (OBGYN) resident comfort with performing a salpingectomy at cesarean delivery after a simulation workshop utilizing a low-cost, easy-to-construct model.

Methods: OBGYN residents were taught how to counsel a patient on a salpingectomy and perform the steps of the procedure utilizing our simulation model. We performed a pre- and post- survey.

Personalising renal function monitoring and interventions in people living with heart failure: protocol for co-designing a care pathway in the RENAL-HF programme.

Background: Heart failure affects almost one million people in the UK and is increasing in prevalence. Many drugs used to treat heart failure impair renal function and can lead to hospitalisation. Adverse drug problems can be partially mitigated through regular renal monitoring and optimising of drug dose and choice to prevent deterioration of kidney function.

Proof-of-concept validation of noninvasive detection of cortical spreading depolarization with high-resolution direct current-electroencephalography with future device recommendations.

Cortical spreading depolarization (SD) is increasingly recognized as a major contributor to secondary brain injury. Noninvasive SD monitoring would enable the institution of SD-based therapeutics. Our primary objective is to establish proof-of-concept validation that scalp direct-current (DC)-potentials can provide noninvasive SD detection by comparing scalp DC-shifts from a high-density electrode array to SDs detected by gold-standard electrocorticography (ECoG).

FakeRotLib: Expedient Noncanonical Amino Acid Parametrization in Rosetta.

Noncanonical amino acids (NCAAs) occupy an important place, both in natural biology and in synthetic applications. However, modeling these amino acids still lies outside the capabilities of most deep learning methods due to sparse training data sets for this task. Instead, biophysical methods such as Rosetta can excel in modeling NCAAs.

Modeling protein conformational ensembles by guiding AlphaFold2 with Double Electron Electron Resonance (DEER) distance distributions.

We describe a modified version of AlphaFold2 that incorporates experimental distance distributions into the network architecture for protein structure prediction. Harnessing the OpenFold platform, we fine-tune AlphaFold2 on structurally dissimilar proteins to explicitly model distance distributions between spin labels determined from Double Electron-Electron Resonance (DEER) spectroscopy. We benchmark the performance of the modified AlphaFold2, refer to as DEERFold, in switching the predicted conformations of a set of membrane transporters using experimental DEER distance distributions.

Multimorbidity in Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Background: Multimorbidity (the presence of multiple long-term conditions) increases the complexity of management decisions for patients presenting with acute coronary syndrome (ACS).

Objectives: The purpose of this study was to ascertain the prevalence of multimorbidity in ACS and assess its impact on clinical management and outcomes.

Methods: Medline, Web of Science, Embase, and Cochrane were searched to July 2024 for studies that reported: 1) the prevalence of multimorbidity in patients with incident ACS or 2) ACS management and/or clinical outcomes, stratified by multimorbidity status.

Long-term effectiveness of non-surgical interventions for chronic low back pain: a systematic review and meta-analysis.

Background: Chronic low back pain is a long-term recurrent condition. Interventions with sustained benefits are needed to reduce the associated personal and societal burden. We aimed to assess the long-term effectiveness of non-surgical interventions for reducing pain intensity and disability in adults with chronic low back pain.

Seven Opportunities for Artificial Intelligence in Primary Care Electronic Visits: Qualitative Study of Staff and Patient Views.

Purpose: Increased workload associated with electronic visits (eVisits) in primary care could potentially be decreased by the use of artificial intelligence (AI); however, it is unknown whether this use of AI would be acceptable to staff and patients. We explored patient and primary care staff views on the use of and opportunities for AI during eVisits.

Methods: We conducted semistructured interviews and focus groups with primary care staff (n = 16) and patients (n = 37) from primary care practices in northwest England and London (n = 14) using the Patchs eVisits system (Patchs Health Limited; ) from May 2020 to September 2021.

Seasonal nutrient contribution of mangrove aquatic foods to fisher households in West Kalimantan, Indonesia.

Background: Aquatic foods are micronutrient-rich and utilised by coastal communities across the globe. However, the contribution of aquatic foods sourced from mangroves to nutrient intake is relatively unknown, despite thousands of people reliant on their resources in coastal regions across the globe. This case study aimed to quantify the nutrient contribution that aquatic foods make to mangrove fishers' household dietary requirements in a community in West Kalimantan, Indonesia.

What are the consequences of musculoskeletal pain in adolescents? A critical qualitative systematic review and meta-synthesis.

There is a paucity of research into the lived experiences of adolescents with musculoskeletal pain. This study synthesised the available qualitative research on musculoskeletal pain consequences in adolescents. CINAHL, EMBASE, MEDLINE, PsycINFO and Research Rabbit were searched, and a critical qualitative systematic review and meta-synthesis was performed (Prospero ID=476626).

Weather extremes and their impact on crop transportation networks: Evidence from U.S. Midwestern elevators.

The grain price margins between buyers and sellers (i.e., basis spread) is influenced by the infrastructure used to transport crops from collection points to ports, which can be disrupted by weather extremes like floods and severe storms.

Health information management professionals' investigator involvement in research: barriers and facilitators.

Background: Research underpins and informs a profession's growth. Research and practice have a fundamental relationship involving knowledge production and its applications to a profession's work.

Objectives: To investigate health information management professionals': interest in investigator involvement in research; exposure to, or opportunity for, research investigator involvement; areas of research interest; barriers to research investigator involvement.

FakeRotLib: expedient non-canonical amino acid parameterization in Rosetta.

Non canonical amino acids (NCAAs) occupy an important place, both in natural biology and synthetic applications. However, modeling these amino acids still lies outside the capabilities of most deep learning methods due to sparse training datasets for this task. Instead, biophysical methods such as Rosetta can excel in modeling NCAAs.

Improving audit and feedback: A user-centred approach to designing feedback techniques for an online experiment.

Audit and feedback (A&F) programmes aim to improve patient care by providing summary data on performance to clinicians. They generally have modest, but variable, effects on patient care and questions remain about how best to provide performance feedback. It is not feasible to test all ways of providing feedback in 'real-world' randomised trials.

Medical policy determinations for pharmacogenetic tests among US health plans.

Objectives: To evaluate medical policy determinations for pharmacogenetic (PGx) testing for 65 clinically relevant drug-gene pairs and evidence cited to support determinations across major US health plans and laboratory benefit managers (LBMs).

Study Design: Landscape analysis of available PGx medical policies to determine coverage status of certain drug-gene pairs.

Methods: PGx medical policies as of February 1, 2024, were ascertained through Policy Reporter for top national insurers, LBMs, and the Palmetto GBA Molecular Diagnostic Services (MolDX) Program, which determines whether a molecular diagnostic test is covered by Medicare.

Enantioselective Protein Affinity Selection Mass Spectrometry (E-ASMS).

We report an enantioselective protein affinity selection mass spectrometry screening approach (E-ASMS) that enables the detection of weak binders, informs on selectivity, and generates orthogonal confirmation of binding. After method development with control proteins, we screened 31 human proteins against a designed library of 8,210 chiral compounds. 16 binders to 12 targets, including many proteins predicted to be "challenging to ligand", were discovered and confirmed in orthogonal biophysical assays.

Interpretable Deep-Learning p Prediction for Small Molecule Drugs via Atomic Sensitivity Analysis.

Machine learning (ML) models now play a crucial role in predicting properties essential to drug development, such as a drug's logscale acid-dissociation constant (p). Despite recent architectural advances, these models often generalize poorly to novel compounds due to a scarcity of ground-truth data. Further, these models lack interpretability.

A Retrospective Analysis of 190 Patients With Scoliosis Referred to a Private Australian Clinical Advisory Service Between 2017 and 2020.

Objective: The aim of this study was to describe the demographic and clinical characteristics of patients with scoliosis from Australian primary care practices.

Methods: A retrospective review of 190 patient records from August 2017 to April 2020 from a private Australian clinical advisory service database was performed. Deidentified demographic and clinical data were collated and analyzed, along with information regarding the referring practitioners and any accompanying clinical or paraclinical information.

Association that Neuroimaging and Clinical Measures Have with Change in Arm Impairment in a Phase 3 Stroke Recovery Trial.

Objective: Vagus nerve stimulation (VNS) paired with rehabilitation therapy improved motor status compared to rehabilitation alone in the phase III VNS-REHAB stroke trial, but treatment response was variable and not associated with any clinical measures acquired at baseline, such as age or side of paresis. We hypothesized that neuroimaging measures would be associated with treatment-related gains, examining performance of regional injury measures versus global brain health measures in parallel with clinical measures.

Methods: Baseline magnetic resonance imaging (MRI) scans in the VNS-REHAB trial were used to derive regional injury measures (extent of injury to corticospinal tract, the primary regional measure; plus extent of injury to precentral gyrus and postcentral gyrus; lesion volume; and lesion topography) and global brain health measures (degree of white matter hyperintensities, the primary global brain measure; plus volumes of cerebrospinal fluid, cortical gray matter, white matter, each thalamus, and total brain).

Audit and Feedback Interventions for Antibiotic Prescribing in Primary Care: A Systematic Review and Meta-analysis.

Background: This systematic review evaluates the effect of audit and feedback (A&F) interventions targeting antibiotic prescribing in primary care and examines factors that may explain the variation in effectiveness.

Methods: Randomized controlled trials (RCTs) involving A&F interventions targeting antibiotic prescribing in primary care were included in the systematic review. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and ClinicalTrials.

Proof-of-Concept Validation of Noninvasive Detection of Cortical Spreading Depolarization with High Resolution Direct Current-Electroencephalography with Future Device Recommendations.

Background/objective: Cortical spreading depolarization (SD) is increasingly recognized as a major contributor to secondary brain injury. Noninvasive SD monitoring would enable the institution of SD-based therapeutics. Our primary objective is to establish proof-of-concept validation that scalp DC-potentials can provide noninvasive SD detection by comparing scalp direct-current (DC)-shifts from a high-density electrode array to SDs detected by gold-standard electrocorticography (ECoG).