BCG-Induced DNA Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing the Risk for Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Background: The BCG vaccine induces trained immunity, an epigenetic-mediated increase in innate immune responsiveness. Therefore, this clinical trial evaluated if BCG-induced trained immunity could decrease coronavirus disease 2019 (COVID-19)-related frequency or severity.

Methods: A double-blind, placebo-controlled clinical trial of healthcare workers randomized participants to vaccination with BCG TICE or placebo (saline).

Association between governmental spending on social services and health care use among low-income older adults.

Prior research demonstrates that local government spending on social policies, excluding health care, is linked to improved population health. Whether such spending is associated with better access to primary care and reduced acute care utilization remains unclear. In this cross-sectional study, we evaluated the associations between county-level social spending and individual-level health care utilization among low-income Medicare beneficiaries, aged ≥65 years, from 2016 to 2018.

On the substrate turnover rate of NBCe1 and AE1 SLC4 transporters: structure-function considerations.

A transport protein's turnover rate (TOR) is the maximum rate of substrate translocation under saturating conditions. This parameter represents the number of transporting events per transporter molecule (assuming a single transport site) per second (s). From this standpoint, a transporter's TOR is similar to an enzyme's catalytic constant.

Medicare Resource Use Differs by English Reading Proficiency.

Background And Objectives: Medicare coverage decisions are complex. The Centers for Medicare & Medicaid Services (CMS) provides a hotline, handbook, and website to help Medicare beneficiaries understand their benefits and coverage options, yet it is unclear what factors affect beneficiary use of these resources. We examined limited English speaking and English reading proficiency status as predictors of CMS Medicare informational resource use in a nationally representative sample of Medicare beneficiaries.

β-Caryophyllene and Statins in Bone Fracture Healing - A Narrative Review.

Bone fractures are a leading cause of morbidity and healthcare expenditure globally. The complex healing process involves inflammation, cartilage formation, mineralization, and bone remodeling. Current treatments like immobilization, surgery, and bone grafting, though effective, pose significant challenges, such as prolonged recovery and high costs.

Racial Disparities in Time to Huntington Disease Diagnosis in North America: An ENROLL-HD Analysis.

Background And Objectives: There are well-documented racial and ethnic disparities in access to neurologic care and disease-specific outcomes. Although contemporary clinical and neurogenetic understanding of Huntington disease (HD) is thanks to a decades-long study of a Venezuelan cohort, there are a limited number of studies that have evaluated racial and ethnic disparities in HD. The goal of this study was to evaluate disparities in time from symptom onset to time of diagnosis of HD.

Environment scan of generative AI infrastructure for clinical and translational science.

This study reports a comprehensive environmental scan of the generative AI (GenAI) infrastructure in the national network for clinical and translational science across 36 institutions supported by the CTSA Program led by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) at the United States. Key findings indicate a diverse range of institutional strategies, with most organizations in the experimental phase of GenAI deployment. The results underscore the need for a more coordinated approach to GenAI governance, emphasizing collaboration among senior leaders, clinicians, information technology staff, and researchers.

Preterm Labor and Hypertensive Disorders in Adolescent Pregnancies With Diabetes Between 2006 and 2019.

Objective: We sought to evaluate the risk of preterm labor and hypertensive disorders in adolescent pregnancies with and without diabetes.

Methods: We evaluated 1,843,139 adolescents (≤20 years old) with labor and delivery admissions in the national Kids' Inpatient Database (KID) in years 2006, 2009, 2012, 2016, and 2019. International classification of disease codes was used to identify diabetes and medical factors affecting pregnancy.

Considerable decline in prostate cancer mortality in Nordic countries after 2000.

Background And Purpose: In the late 1990s, the Nordic countries, with Norway at the top, were among the countries with the highest prostate cancer mortality in the world. We present updated mortality rates from the Nordic countries and discuss possible interpretations of changes in trends.

Material And Methods: Age-standardized rates for prostate-specific mortality in 1985-2022, estimated lifetime risk of death (0-84 years) and annual changes in mortality were obtained from the NORDCAN database.

Assessing the Return of Function After Various Approaches to Stable Fixation of Metacarpal Fractures.

Background: Multiple approaches exist for operative fixation of metacarpal fractures; with common treatments including lag screw fixation or open-reduction internal fixation (ORIF) with plates and screws. Recently, the adaptation of intramedullary screw (IMS) placement has allowed for an essentially closed approach with stable fixation and theoretically improved outcomes. Thus, we sought to compare such approaches to ultimately determine the superior method for achieving the goal of return to normal function.

The multi-omics signatures of telomere length in childhood.

Background: Telomere length is an important indicator of biological age and a complex multi-factor trait. To date, the telomere interactome for comprehending the high-dimensional biological aspects linked to telomere regulation during childhood remains unexplored. Here we describe the multi-omics signatures associated with childhood telomere length.

Factors Associated with Low/Moderate Perceived Risk for HIV Acquisition Among Gay, Bisexual, and Other Men Who Have Sex with Men Eligible to Use Pre-exposure Prophylaxis from Brazil, Mexico, and Peru.

Perceived risk for HIV acquisition among gay, bisexual, and other men who have sex with men (GBMSM) may not align with their actual sexual HIV exposure. Factors associated with low/moderate perceived risk among GBMSM eligible for pre-exposure prophylaxis (PrEP) (based on their high estimated HIV exposure) have been poorly described in Latin America. This is a secondary analysis of a 2018 web-based cross-sectional survey in Brazil, Mexico, and Peru.

Cryogenic in-memory computing using magnetic topological insulators.

Machine learning algorithms have proven to be effective for essential quantum computation tasks such as quantum error correction and quantum control. Efficient hardware implementation of these algorithms at cryogenic temperatures is essential. Here we utilize magnetic topological insulators as memristors (termed magnetic topological memristors) and introduce a cryogenic in-memory computing scheme based on the coexistence of a chiral edge state and a topological surface state.

Rome Foundation Working Team Report on overlap in disorders of gut-brain interaction.

In patients with disorders of gut-brain interaction (DGBI), overlapping non-gastrointestinal conditions such as fibromyalgia, headaches, gynaecological and urological conditions, sleep disturbances and fatigue are common, as is overlap among DGBI in different regions of the gastrointestinal tract. These overlaps strongly influence patient management and outcome. Shared pathophysiology could explain this scenario, but details are not fully understood.

Comparison of software-assisted and freehand methods of rotational assessment for diaphyseal tibia fractures.

Objective: Accurate rotational reduction following tibial shaft fracture fixation is absent in up to 36% of cases yet may be critical for lower extremity biomechanics. The objective of this cadaveric study was to compare the results of freehand methods of reduction with software-assisted reduction.

Methods: Four fellowship-trained orthopaedic trauma surgeons attempted rotational correction in a cadaveric model with fluoroscopic assistance (without radiographic visualization of the fracture site) using (1) their method of choice (MoC) and (2) software assistance (SA).

The politicization of influenza: partisan changes in flu vaccination before and after COVID-19.

Background: Democrats are more likely to be vaccinated for COVID-19 than Republicans. It is unknown if political polarization surrounding the COVID-19 vaccine has affected flu vaccine uptake. The purpose of this study is to examine the partisan differences in annual flu vaccine uptake before and after the COVID-19 pandemic.

Positive affect amplifies integration within episodic memories in the laboratory and the real world.

Emotional events hold a privileged place in our memories, differing in accuracy and structure from memories for neutral experiences. Although much work has focused on the pronounced differences in memory for negative experiences, there is growing evidence that positive events may lead to more holistic, or integrated, memories. However, it is unclear whether these affect-driven changes in memory structure, which have been found in highly controlled laboratory environments, extend to real-world episodic memories.

Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors.

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma.

Botensilimab (Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti-PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas.

Purpose: Outcomes for patients with advanced sarcomas are poor and there is a high unmet need to develop novel therapies. The purpose of this phase I study was to define the safety and efficacy of botensilimab (BOT), an Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody, plus balstilimab (BAL), an anti-PD-1 antibody, in advanced sarcomas.

Methods: BOT was administered intravenously (IV) at 1 mg/kg or 2 mg/kg once every 6 weeks in combination with BAL IV at 3 mg/kg once every 2 weeks for up to 2 years.

Comprehensive guide for epigenetics and transcriptomics data quality control.

Host response to environmental exposures such as pathogens and chemicals can include modifications to the epigenome and transcriptome. Improved signature discovery, including the identification of the agent and timing of exposure, has been enabled by advancements in assaying techniques to detect RNA expression, DNA base modifications, histone modifications, and chromatin accessibility. The interrogation of the epigenome and transcriptome cascade requires analyzing disparate datasets from multiple assay types, often at single-cell resolution, derived from the same biospecimen.

Update on Hepatorenal Syndrome: From Pathophysiology to Treatment.

Hepatorenal syndrome-acute kidney injury (HRS-AKI) occurs in the setting of advanced chronic liver disease, portal hypertension, and ascites. HRS-AKI is found in ∼20% of patients presenting to the hospital with AKI, but it may coexist with other causes of AKI and/or with preexisting chronic kidney disease, thereby making the diagnosis challenging. Novel biomarkers such as urinary neutrophil gelatinase-associated lipocalin may be useful.

Update on HIV Chemoprevention.

Despite rapid advances in the field of HIV prevention and treatment, unacceptably high global HIV incidence rates highlight the ongoing need for effective HIV prevention interventions for populations at risk for HIV acquisition. This article provides an updated review of the current data surrounding HIV prevention strategies, including treatment as prevention (TasP), preexposure prophylaxis (PrEP), and postexposure prophylaxis (PEP), as well as advances in sexually transmitted infection biomedical prevention. This review provides an overview of the multiple PrEP modalities that are available globally, such as oral PrEP, injectable cabotegravir, and the dapivirine vaginal ring, and describes their respective clinical trials, efficacies, and regulatory approvals.

Impact of Race/Ethnicity on Clinical and Genomic Characteristics, Trial Participation, and Genotype-Matched Therapy among Patients with Metastatic Breast Cancer.

Background: Race/ethnicity may affect outcomes in metastatic breast cancer (MBC) due to biological and social determinants. We evaluated the impact of race/ethnicity on clinical, socioeconomic, and genomic characteristics, clinical trial participation, and receipt of genotype-matched therapy among patients with MBC.

Methods: A retrospective study of patients with MBC who underwent cell-free DNA testing (cfDNA, Guardant360â, 74 gene panel) between 11/2016 and 11/2020 was conducted.