Toward expert-level medical question answering with large language models.

Large language models (LLMs) have shown promise in medical question answering, with Med-PaLM being the first to exceed a 'passing' score in United States Medical Licensing Examination style questions. However, challenges remain in long-form medical question answering and handling real-world workflows. Here, we present Med-PaLM 2, which bridges these gaps with a combination of base LLM improvements, medical domain fine-tuning and new strategies for improving reasoning and grounding through ensemble refinement and chain of retrieval.

Evaluation of Peer Review of Percutaneous Coronary Intervention Operator Performance.

Background: Case-based peer review of percutaneous coronary intervention (PCI) is used by many hospitals for quality improvement and to make decisions regarding physician competency. However, there are no studies testing the reliability or validity of peer review for PCI performance evaluation.

Methods: We recruited interventional cardiologists from 12 Veterans Affairs Health System facilities throughout the United States to provide PCI cases for review.

MRI-based morphometric structural changes correlate with histopathology in experimental autoimmune encephalomyelitis.

Background And Objectives: Magnetic resonance imaging (MRI) and neurohistopathology are important correlates for evaluation of disease progression in multiple sclerosis (MS). Here we used experimental autoimmune encephalomyelitis (EAE) as an animal model of MS to determine the correlation between clinical EAE severity, MRI and histopathological parameters.

Methods: N = 11 female C57BL/6J mice were immunized with human myelin oligodendrocyte glycoprotein 1-125, while N = 9 remained non-immunized.

The distinctive mechanical and structural signatures of residual force enhancement in myofibers.

In muscle, titin proteins connect myofilaments together and are thought to be critical for contraction, especially during residual force enhancement (RFE) when steady-state force is elevated after an active stretch. We investigated titin's function during contraction using small-angle X-ray diffraction to track structural changes before and after 50% titin cleavage and in the RFE-deficient, titin mutant. We report that the RFE state is structurally distinct from pure isometric contractions, with increased thick filament strain and decreased lattice spacing, most likely caused by elevated titin-based forces.

Molecular Identification of Etiological Agents in Fungal and Bacterial Skin Infections: United States, 2020-2024.

: Cutaneous infections of fungal and bacterial origins are common. An accurate diagnosis-especially concerning pathogens that are difficult to isolate on culture-can be achieved using molecular methods (PCR) with a short turnaround time. : We reviewed records of skin specimens (superficial scrapings) submitted by dermatologists across the United States with a clinically suspected dermatitis.

An evaluation of autonomic and gastrointestinal symptoms, and gastric emptying, in patients with systemic sclerosis.

Objective: Assessment of gastrointestinal and autonomic symptoms in patients with systemic sclerosis, and possible associations with gastric emptying rate.

Methods: Participant and patient disease-related characteristics were collected. Gastrointestinal and autonomic symptoms were assessed by the UCLA-SCTC GIT 2.

Promising strategies for the prevention of alcohol-related brain damage through optimised management of acute alcohol withdrawal: A focussed literature review.

There is an increasing awareness of the link between chronic alcohol consumption and the development of cognitive, behavioural and functional deficits. Currently, preventative strategies are limited and require engagement in dedicated long-term rehabilitation and sobriety services, the availability of which is low. The acute alcohol withdrawal syndrome is an episode of neurochemical imbalance leading to autonomic dysregulation, increased seizure risk and cognitive disorientation.

In defense of in vitro fertilization: time to get involved in state-level advocacy!

We share experiences in advocating to defend in vitro fertilization (IVF) in Virginia, Missouri, and Mississippi; provide historical context on the "Personhood" anti-IVF movement; and discuss why "embryo donation" is a more accurate term than "embryo adoption." Some individuals and communities have a deeply held belief that a fertilized oocyte is a very early human life, and we will likely never change their minds. In the fertility community, most providers consider embryos to be an important part of the continuum between gametes (sperm and eggs) to live birth.

The epithelial barrier theory and its associated diseases.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide.

A multimodal treatment of basilar artery re-occlusion - case report.

Background: Stroke due to basilar artery occlusion (BAO) is a severe neurovascular condition with only recently proven effectiveness of mechanical thrombectomy as treatment. Early re-occlusion of the basilar artery (RE-BAO) is an even more challenging form of stroke to treat, associated with poor outcomes and still no optimal treatment guidelines. There are only a few reported cases covering this topic thus far.

Functional prediction of response to therapy prior to therapeutic intervention is associated with improved survival in patients with high-grade glioma.

Patients with high-grade glioma (HGG) have an extremely poor prognosis compounded by a lack of advancement in clinical care over the past few decades. Regardless of classification, most newly diagnosed patients receive the same treatment, radiation and temozolomide (RT/TMZ). We developed a functional precision oncology test that prospectively identifies individual patient's response to this treatment regimen.

Biological and Procedural Predictors of Outcome in the Stroke Preclinical Assessment Network (SPAN) Trial.

Background: The SPAN trial (Stroke Preclinical Assessment Network) is the largest preclinical study testing acute stroke interventions in experimental focal cerebral ischemia using endovascular filament middle cerebral artery occlusion (MCAo). Besides testing interventions against controls, the prospective design captured numerous biological and procedural variables, highlighting the enormous heterogeneity introduced by the multicenter structure that might influence stroke outcomes. Here, we leveraged the unprecedented sample size achieved by the SPAN trial and the prospective design to identify the biological and procedural variables that affect experimental stroke outcomes in transient endovascular filament MCAo.

Degron-Based bioPROTACs for Controlling Signaling in CAR T Cells.

Chimeric antigen receptor (CAR) T cells have made a tremendous impact in the clinic, but potent signaling through the CAR can be detrimental to treatment safety and efficacy. The use of protein degradation to control CAR signaling can address these issues in preclinical models. Existing strategies for regulating CAR stability rely on small molecules to induce systemic degradation.

Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context.

Background: Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence.

Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure.

In striated muscle, the sarcomeric protein myosin-binding protein-C (MyBP-C) is bound to the myosin thick filament and is predicted to stabilize myosin heads in a docked position against the thick filament, which limits crossbridge formation. Here, we use the homozygous Mybpc2 knockout (C2) mouse line to remove the fast-isoform MyBP-C from fast skeletal muscle and then conduct mechanical functional studies in parallel with small-angle X-ray diffraction to evaluate the myofilament structure. We report that C2 fibers present deficits in force production and calcium sensitivity.

A TrkB and TrkC partial agonist restores deficits in synaptic function and promotes activity-dependent synaptic and microglial transcriptomic changes in a late-stage Alzheimer's mouse model.

Introduction: Tropomyosin related kinase B (TrkB) and C (TrkC) receptor signaling promotes synaptic plasticity and interacts with pathways affected by amyloid beta (Aβ) toxicity. Upregulating TrkB/C signaling could reduce Alzheimer's disease (AD)-related degenerative signaling, memory loss, and synaptic dysfunction.

Methods: PTX-BD10-2 (BD10-2), a small molecule TrkB/C receptor partial agonist, was orally administered to aged London/Swedish-APP mutant mice (APP) and wild-type controls.

Decoding Immuno-Competence: A Novel Analysis of Complete Blood Cell Count Data in COVID-19 Outcomes.

Background: While 'immuno-competence' is a well-known term, it lacks an operational definition. To address this omission, this study explored whether the temporal and structured data of the complete blood cell count (CBC) can rapidly estimate immuno-competence. To this end, one or more ratios that included data on all monocytes, lymphocytes and neutrophils were investigated.

Acoustic Enrichment of Heterogeneous Circulating Tumor Cells and Clusters from Metastatic Prostate Cancer Patients.

Background: There are important unmet clinical needs to develop cell enrichment technologies to enable unbiased label-free isolation of both single cell and clusters of circulating tumor cells (CTCs) manifesting heterogeneous lineage specificity. Here, we report a pilot study based on the microfluidic acoustophoresis enrichment of CTCs using the CellSearch CTC assay as a reference modality.

Methods: Acoustophoresis uses an ultrasonic standing wave field to separate cells based on biomechanical properties (size, density, and compressibility), resulting in inherently label-free and epitope-independent cell enrichment.

Hypertension Severity and Declines in Left Ventricular Ejection Fraction Among Women Receiving Adjuvant Chemotherapy for Breast Cancer (WF-97415 UPBEAT).

Background: Hypertension is a risk factor for experiencing left ventricular ejection fraction (LVEF) declines during receipt of potentially cardiotoxic breast cancer (BC) treatment. We sought to determine whether the hypertension stage is associated with LVEF decline during BC treatment.

Methods: Across 24 centers, cardiac magnetic resonance measures of LVEF and brachial arterial blood pressure (BP) measurements were performed in women with stages I to III BC before and 3 months after initiating potentially cardiotoxic chemotherapy.

Myosin-binding protein C regulates the sarcomere lattice and stabilizes the OFF states of myosin heads.

Muscle contraction is produced via the interaction of myofilaments and is regulated so that muscle performance matches demand. Myosin-binding protein C (MyBP-C) is a long and flexible protein that is tightly bound to the thick filament at its C-terminal end (MyBP-C), but may be loosely bound at its middle- and N-terminal end (MyBP-C) to myosin heads and/or the thin filament. MyBP-C is thought to control muscle contraction via the regulation of myosin motors, as mutations lead to debilitating disease.