Low Utility of Routine Thyroid Function Testing for Bowel Symptoms: A Population-Based Assessment.

Background: Chronic constipation, diarrhea, and fecal incontinence (FI) are prevalent with significant impact on quality of life and healthcare utilization. Thyroid dysfunction was recognized as a potential contributor to bowel disturbances in selected populations, but the strength/consistency of this association remain unclear.

Aims: To investigate the relationship between thyroid function and bowel health measures (constipation, diarrhea, and FI) in a nationally representative sample of the U.

Multi-gate neuron-like transistors based on ensembles of aligned nanowires on flexible substrates.

The intriguing way the receptors in biological skin encode the tactile data has inspired the development of electronic skins (e-skin) with brain-inspired or neuromorphic computing. Starting with local (near sensor) data processing, there is an inherent mechanism in play that helps to scale down the data. This is particularly attractive when one considers the huge data produced by large number of sensors expected in a large area e-skin such as the whole-body skin of a robot.

Targeting ultra-processed foods for prevention of type 2 diabetes: state of the evidence and future directions.

The incidence of type 2 diabetes has risen globally, in parallel with the obesity epidemic and environments promoting a sedentary lifestyle and low-quality diet. There has been scrutiny of ultra-processed foods (UPFs) as a driver of type 2 diabetes, underscored by their increasing availability and intake worldwide, across countries of all incomes. This narrative review addresses the accumulated evidence from investigations of the trends in UPF consumption and the relationship with type 2 diabetes incidence.

Impact of Recent Translational and Therapeutic Developments on Clinical Course of BCR::ABL1-Positive and -Negative Myeloproliferative Neoplasms.

Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues.

Characterization of the Phenotypic Consequences of the Duffy-Null Genotype.

A wealth of research focused on African American populations has connected rs2814778-CC ("Duffy-null") to decreased neutrophil (neutropenia) and leukocyte counts (leukopenia). While it has been proposed that this variant is benign, prior studies have shown that the misinterpretation of Duffy-null associated neutropenia and leukopenia can lead to unnecessary bone marrow biopsies, inequities in cytotoxic and chemotherapeutic treatment courses, under-enrollment in clinical trials, and other disparities. To investigate the phenotypic correlates of Duffy-null status, we conducted a phenome-wide association study (PheWAS) across more than 1,400 clinical conditions in All of Us, the Vanderbilt University Medical Center's Biobank, and the Million Veteran Program.

Structuring Palliative Care Education for Medical Students: Impact of a Novel Framework and Pocket Card.

Introduction: Palliative care (PC) education is not uniformly provided across U.S. medical schools.

Assessment and Reporting of Extraintestinal Manifestations and Fatigue in Phase 3 Inflammatory Bowel Disease Clinical Trials.

Background: Extraintestinal Manifestations (EIMs) of Inflammatory Bowel Disease (IBD) are frequently experienced by patients and may lead to severe symptoms and fatigue. However, the reporting patterns of these outcomes in IBD randomized controlled trials (RCTs) is not clear.

Methods: We searched placebo controlled phase 3 RCTs of advanced therapies in IBD and assessed the frequency and means of reporting EIM and fatigue data in these studies.

Disparities in utilization of novel cancer therapies in advanced stage III and IV melanoma and variance in outcomes.

Introduction: Significant gains in advanced melanoma have been made through immunotherapy trials. Factors influencing equitable access and survival impact of these novel therapies are not well-defined.

Method: Retrospective analysis using National Cancer Database of patients with advanced stage III and IV melanoma from 2004 to 2021.

Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets.

Background: Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state specific targetable cell-surface proteins.

Methods: We characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES-dominant to define subtype-specific and pan-neuroblastoma gene sets.

Quantitative Pupillometry Predicts Neurologic Deterioration in Patients with Large Middle Cerebral Artery Stroke.

Objective: This study assesses whether longitudinal quantitative pupillometry predicts neurological deterioration after large middle cerebral artery (MCA) stroke and determines how early changes are detectable.

Methods: This prospective, single-center observational cohort study included patients with large MCA stroke admitted to Boston Medical Center's intensive care unit (2019-2024). Associations between time-to-neurologic deterioration and quantitative pupillometry, including Neurological Pupil Index (NPi), were assessed using Cox proportional hazards models with time-dependent covariates adjusted for age, sex, and Alberta Stroke Program Early CT Score.

New onset refractory status epilepticus: Long-term outcomes beyond seizures.

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps.

Establishing Reference Values in the Neuromuscular Ultrasound Laboratory Using the e-Norms Method: A Feasibility Study.

Introduction/aims: The standard procedure to establish reference values in a neuromuscular laboratory involves examining healthy controls, as nerve size varies with the population and muscle echo intensity (EI) is device-specific. We aimed to derive these reference values by extrapolation from a studied sample (the e-norms method), compare them with published reference values, and determine their diagnostic accuracy.

Methods: We retrospectively analyzed data from consecutive patients who underwent nerve and/or muscle ultrasound in our ultrasound laboratory, which is a tertiary referral center for neuromuscular diseases in Southern Poland in the years 2018-2023.

Innovative Insurance to Improve US Patient Access to Cell and Gene Therapy.

Unlabelled: Policy Points Cell and gene therapies (CGTs) offer treatment for rare and oftentimes deadly disease, but their prices are high, and payers may seek to limit spending. Total annual costs of covering all existing and expected CGTs for the entire US population 2023-2035 to amount to less than $20 per person and concentrate in commercial and state Medicaid plans. Reinsurance fees add to expected costs.

Bridging Therapies-Ex Vivo Liver Xenoperfusion and the Role of Machine Perfusion: An Update.

Advancements in xenotransplantation intersecting with modern machine perfusion technology offer promising solutions to patients with liver failure providing a valuable bridge to transplantation and extending graft viability beyond current limitations. Patients facing acute or acute chronic liver failure, post-hepatectomy liver failure, or fulminant hepatic failure often require urgent liver transplants which are severely limited by organ shortage, emphasizing the importance of effective bridging approaches. Machine perfusion is now increasingly used to test and use genetically engineered porcine livers in translational studies, addressing the limitations and costs of non-human primate models.

Characterisation of the ocular inflammatory response to AAV reveals divergence by sex and age.

Progress for ocular AAV gene therapy has been hindered by AAV-induced inflammation, limiting dose escalation and long-term efficacy. Broadly, the extent of inflammatory responses alters with age and sex, yet these factors are poorly represented in pre-clinical development of ocular AAV gene therapies. Here, we combined clinical imaging, flow cytometry and bulk-sequencing of sorted microglia to interrogate the longitudinal inflammatory response following intravitreal delivery of AAV2 in young (3-month), middle aged (9-month) and old (18-month) Cx3cr1-creER:R26tdTomato+/- mice of both sexes.

Hypertensive disorders of pregnancy and gestational diabetes mellitus and predicted risk of maternal cardiovascular disease 10-14 years after delivery: A prospective cohort.

Aims: Studies evaluating the relationship between adverse pregnancy outcomes (APOs), namely hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), with the estimated risk of atherosclerotic cardiovascular disease (ASCVD) remains limited and could inform patient-centred decision-making in the postpartum period. We examined whether HDP or GDM were associated with a higher 10- and 30-year predicted risk of ASCVD measured 10-14 years after delivery.

Methods: A secondary analysis from the international prospective Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (2013-2016) cohort.

Implementation effectiveness of 'Problem solving for better health' training in Lesotho using mixed methods and the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) framework.

Background: Healthcare resources have been concentrated in urban areas, leaving rural regions vulnerable to poorer health outcomes. The Problem Solving for Better Health (PSBH) program was implemented to enhance healthcare systems in resource-limited regions by training personnel to maximize existing resources in problem-solving. This study evaluated the implementation effectiveness of PSBH-Nursing (PSBHN), a nationally led initiative to train nurses in PSBH in Lesotho.

Enriched phenotypes in rare variant carriers suggest pathogenic mechanisms in rare disease patients.

Background: The mechanistic pathways that give rise to the extreme symptoms exhibited by rare disease patients are complex, heterogeneous, and difficult to discern. Understanding these mechanisms is critical for developing treatments that address the underlying causes of diseases rather than merely the presenting symptoms. Moreover, the same dysfunctional series of interrelated symptoms implicated in rare recessive diseases may also lead to milder and potentially preventable symptoms in carriers in the general population.

Safety and Efficacy of Deutetrabenazine at High versus Lower Daily Dosages in the ARC-HD Study to Treat Chorea in Huntington Disease.

Background: Huntington disease (HD) is a progressive neurodegenerative disease that causes psychiatric and neurological symptoms, including involuntary and irregular muscle movements (chorea). Chorea can disrupt activities of daily living, pose safety issues, and may lead to social withdrawal. The vesicular monoamine transporter 2 inhibitors tetrabenazine, deutetrabenazine, and valbenazine are approved treatments that can reduce chorea.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.