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.

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.

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.

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.

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.

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.

mtSTAT3 suppresses rheumatoid arthritis by regulating Th17 and synovial fibroblast inflammatory cell death with IL-17-mediated autophagy dysfunction.

Th17 cells are activated by STAT3 factors in the nucleus, and these factors are correlated with the pathologic progression of rheumatoid arthritis (RA). Recent studies have demonstrated the presence of STAT3 in mitochondria, but its function is unclear. We investigated the novel role of mitochondrial STAT3 (mitoSTAT3) in Th17 cells and fibroblast-like synoviocytes (FLSs) and analyzed the correlation of mitoSTAT3 with RA.

Adherence to multi-target stool DNA testing for colorectal cancer screening in the United States.

Purpose: Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA and is highly preventable, with early screening vital for improving outcomes. This study aimed to evaluate adherence rates of multi-target stool DNA (mt-sDNA) testing, following updated guidelines recommending screening starting at age 45.

Methods: This retrospective cohort study used aggregated data from Exact Sciences Laboratories LLC, examining new users (first-time testers) aged 45-85 with commercial, Medicare, or Medicaid insurance who received mt-sDNA test kits (point-of-care) between January 1, 2023, and June 1, 2023.

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity.

Cancer cells frequently rewire their metabolism to support proliferation and evade immune surveillance, but little is known about metabolic targets that could increase immune surveillance. Here we show a specific means of mitochondrial respiratory complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of either Ndufs4 or Ndufs6, but not other CI subunits, induces an immune-dependent growth attenuation in melanoma and breast cancer models.

Role of transforming growth factor-β1 in regulating adipocyte progenitors.

Adipose tissue (AT) metabolism involves coordinating various cells and cellular processes to regulate energy storage, release, and overall metabolic homeostasis. Therein, macrophage and its cytokine are important in controlling tissue homeostasis. Among cytokines, the role of transforming growth factor-β1 (Tgf-β1), a cytokine abundantly expressed in CD206 M2-like macrophage and correlated with the expansion of AT and fibrosis, in AT metabolism, remains unknown.

Oxytocin levels in response to CRH administration in hypopituitarism and hypothalamic damage: a randomized, crossover, placebo-controlled trial.

Increasing evidence supports the presence of oxytocin deficiency (OXT-D) in patients with hypopituitarism and hypothalamic damage (HHD), that might be associated with neuropsychological deficits and sexual dysfunction, leading to worse quality of life (QoL). Therefore, identifying a provocative test to diagnose an OXT-D will be important. Corticotropin-releasing hormone (CRH) is a candidate for such a test as it increases oxytocin secretion in animal models.

Identification of subsurface cavities in urban environment.

Gravimetry is the most suitable geophysical method for identifying subsurface cavities in urban or industrial environments, as it is unaffected by nearby electromagnetic disturbances. In this study, we used gravimetric geophysical method to understand the land subsidence, collapses, and fissures observed around the sealed Albian drilling site located in the M'Rara region of Northeast of Algeria. Particularly, we would like study the geological observed phenomena and its potential association with the presence of a cavity within the salt layer.

Patterns of Klebsiella pneumoniae bacteremic dissemination from the lung.

Bacteremia, a leading cause of death, generally arises after bacteria establish infection in a particular tissue and transit to secondary sites. Studying dissemination from primary sites by solely measuring bacterial burdens does not capture the movement of individual clones. By barcoding Klebsiella pneumoniae, a leading cause of bacteremia, we track pathogen dissemination following pneumonia.

Streptococcus abundance and oral site tropism in humans and non-human primates reflects host and lifestyle differences.

The genus Streptococcus is highly diverse and a core member of the primate oral microbiome. Streptococcus species are grouped into at least eight phylogenetically-supported clades, five of which are found almost exclusively in the oral cavity. We explored the dominant Streptococcus phylogenetic clades in samples from multiple oral sites and from ancient and modern-day humans and non-human primates and found that clade dominance is conserved across human oral sites, with most Streptococcus reads assigned to species falling in the Sanguinis or Mitis clades.

Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.

How Pediatric Readiness can Impact Pediatric Trauma From Every Day to Mass Events.

Disaster events such as weather events and mass casualty events are increasing in frequency and severity. Caring for children during a surge requires a regional approach given limited pediatric inpatient capacity and expertise. During the 2024 American Academy of Pediatrics National Convention and Exhibition, the Section on Surgery and Council on Children and Disasters (COCD) partnered to present a joint symposium emphasizing importance of pediatric readiness and disaster preparedness and role of pediatric trauma surgeons in disaster preparedness and response in all communities.