Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity.

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies.

Clinical Outcomes of Patients With Newly Diagnosed Acute Myeloid Leukemia Receiving Treatment in a Safety-Net Hospital System.

Background: 'Standard of care' therapies for adult acute myeloid leukemia (AML) have yielded 5-year overall survival (OS) rates of 30%-45 %. Risk stratification and novel targeted therapies have improved 5-year OS rates to >75 % for certain groups in specialized centers.

Patients And Methods: This is a retrospective cohort analysis of outcomes in patients ≥18 years with newly diagnosed AML treated between 2005 and 2019 in the Harris Health County, Safety-Net Hospital System in Houston, TX.

Improving outcomes for care partners of individuals with traumatic brain injury: Results for a mHealth randomized control trial of the CareQOL app.

Objective: To test the efficacy of a randomized control trial low-touch mobile health intervention designed to promote care partner self-awareness and self-care.

Design: This randomized controlled trial (RCT) included a baseline assessment of self-report surveys of health-related quality of life (HRQOL), care partner-specific outcomes, and the functional/mental status of the person with TBI, as well as a 6-month home monitoring period that included three daily questions about HRQOL, monthly assessments of 12 HRQOL domains, and the use of a Fitbit® to continuously monitor physical activity and sleep. HRQOL surveys were repeated at 3- and 6-months post-home monitoring.

High intensity approaches to exposure and response prevention for obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric condition with multidetermined etiological and maintaining mechanisms. Cognitive behavioral therapy (CBT), specifically exposure and response prevention (ERP), is the first line behavioral intervention to treat OCD. ERP directly targets threat learning that characterizes OCD through processes of habituation (fear extinction) and inhibitory learning, in addition to eliciting neuronal changes implicated in OCD.

Diagnostic Accuracy of Imperforate Hymen at a Single Referral Center.

Study Objective: Imperforate hymen (IH) is a rare congenital anomaly that results in vaginal outlet obstruction. IH can cause significant morbidity if not managed appropriately, which depends on accurate identification of the condition. However, data on the accuracy of IH diagnosis is limited.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Safety and immunogenicity of ascending doses of influenza A(H7N9) inactivated vaccine with or without MF59®.

Introduction: While it remains impossible to predict the timing of the next influenza pandemic, novel avian influenza A viruses continue to be considered a significant threat.

Methods: A Phase II study was conducted in healthy adults aged 18-64 years to assess the safety and immunogenicity of two intramuscular doses of pre-pandemic 2017 influenza A(H7N9) inactivated vaccine administered 21 days apart. Participants were randomized (n = 105 in each of Arms 1-3) to receive 3.

Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in Advanced Urothelial Carcinoma.

Background: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.

Patients And Methods: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI.

The Society of Thoracic Surgeons (STS) Clinical Practice Guideline on Surgical Management of Oligometastatic Non-small Cell Lung Cancer.

Background: The use of local consolidative therapy (LCT) in patients with oligometastatic non-small cell lung cancer (NSCLC) is rapidly evolving, with a preponderance of data supporting the benefits of such therapeutic approaches incorporating pulmonary resection for appropriately selected candidates. However, practices vary widely institutionally and regionally, and evidence-based guidelines are lacking.

Methods: The Society of Thoracic Surgeons assembled a panel of thoracic surgical oncologists to evaluate and synthesize the available evidence regarding the role of pulmonary resection as LCT.

Current Burden of Lean Metabolic Dysfunction-Associated Steatotic Liver Disease Among US Adults, 2017-2023.

Our study investigated the prevalence of lean steatotic liver disease (SLD) and its subcategories, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-related and alcohol-related SLD (MetALD), and alcohol-related liver disease (ALD) among lean adults in the US. Analysing data from 2965 lean adults (≥ 18 years) from the National Health and Nutrition Examination Survey (2017-2023), we found the age-adjusted prevalence of lean SLD to be 12.8%.

Integration of multiomic data identifies core-module of inherited-retinal diseases.

Human diseases with similar phenotypes can be interconnected through shared biological pathways, genes, or molecular mechanisms. Inherited retinal diseases (IRDs) cause photoreceptor dysfunction due to mutations in approximately 300 genes, affecting visual transduction, photoreceptor morphogenesis, and transcription factors, suggesting common pathobiological mechanisms. This study examined the functional relationship between known IRDs genes by integrating binding sites and gene expression data from the key photoreceptor transcription factors (TFs), Crx and Nrl.

Predictive Value of FDG Uptake on PET for Future Immune Checkpoint Inhibitor-Mediated Colitis: A Case Series.

: Immune-mediated colitis (IMC) is a common immune-related adverse event during immune checkpoint inhibitor (ICI) therapy. This case series and review aimed to highlight atypical cases of IMC and explore the potential of PET/CT to predict imminent ICI colitis. : Through a descriptive, retrospective study at a tertiary cancer center, we identified adult patients receiving ICIs for any cancer between 2010 and 2022 who also underwent PET/CT for routine cancer surveillance during this time.

Role of Mutation in the Development of Eleven Different Cancers.

: With the rise in prevalence of diagnostic genetic techniques like RNA sequencing and whole exome sequencing (WES), as well as biological treatment regiments for cancer therapy, several genes have been implicated in carcinogenesis. This review aims to update our understanding of the Neurofibromatosis 2 (NF2) gene and its role in the pathogenesis of various cancers. : A comprehensive search of five online databases yielded 43 studies that highlighted the effect of sporadic NF2 mutations on several cancers, including sporadic meningioma, ependymoma, schwannoma, mesothelioma, breast cancer, hepatocellular carcinoma, prostate cancer, glioblastoma, thyroid cancer, and melanoma.

Exploring Quantitative MRI Biomarkers of Head and Neck Post-Radiation Lymphedema and Fibrosis: Post Hoc Analysis of a Prospective Trial.

Background: Quantifying head and neck lymphedema and fibrosis (HN-LEF) is crucial in the investigation and management of treatment sequelae in head and neck cancer (HNC).

Methods: The T1- and T2-weighted MRI signal intensity (SI) was examined in relation to HN-LEF categories per physical/tactile examination (No-LEF, A-B = edema, C = edema + fibrosis, D = fibrosis), and MRI structural volumes were examined in relation to a novel 10-point HN-LEF score in the intraoral and submental regions.

Results: We identified differences in ranks among HN-LEF categories in relation to the MRI SI (A-B and C are higher than D and No-LEF for T2 SI, and A-B is the highest for T1).

Girolline is a sequence context-selective modulator of eIF5A activity.

Natural products have a long history of providing probes into protein biosynthesis, with many of these compounds serving as therapeutics. The marine natural product girolline has been described as an inhibitor of protein synthesis. Its precise mechanism of action, however, has remained unknown.

Proficiency, Clarity, and Objectivity of Large Language Models Versus Specialists' Knowledge on COVID-19 Impacts in Pregnancy: A Cross-Sectional Pilot Study.

Background: The COVID-19 pandemic has significantly strained healthcare systems globally, leading to an overwhelming influx of patients and exacerbating resource limitations. Concurrently, an "infodemic" of misinformation, particularly prevalent in women's health, has emerged. This challenge has been pivotal for healthcare providers, especially gynecologists and obstetricians, in managing pregnant women's health.

Treatment of rapid recurrence of severe steatosis with combined GLP-1 agonist and growth hormone therapy in a pediatric patient transplanted for metabolic dysfunction-associated steatohepatitis cirrhosis in the setting of hypopituitarism.

The association between hypopituitarism and metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized, although data about therapies targeting recurrence post-transplant is limited. An 8-year-old with hypopituitarism-associated MASLD underwent a liver transplant due to rapid progression of metabolic dysfunction-associated steatohepatitis (MASH). Hepatosteatosis recurred within weeks.

Design and implementation of an action plan for justice, equity, diversity, and inclusion within the Clinical Genome Resource.

How might members of a large, multi-institutional research and resource consortium foster justice, equity, diversity, and inclusion as central to its mission, goals, governance, and culture? These four principles, often referred to as JEDI, can be aspirational-but to be operationalized, they must be supported by concrete actions, investments, and a persistent long-term commitment to the principles themselves, which often requires self-reflection and course correction. We present here the iterative design process implemented across the Clinical Genome Resource (ClinGen) that led to the development of an action plan to operationalize JEDI principles across three major domains, with specific deliverables and commitments dedicated to each. Active involvement of consortium leadership, buy-in from its members at all levels, and support from NIH program staff at pivotal stages were essential to the success of this effort.

Mid-life anti-inflammatory metabolites are inversely associated with long-term cardiovascular disease events.

Background: Preclinical data have shown that low levels of metabolites with anti-inflammatory properties may impact metabolic disease processes. However, the association between mid-life levels of such metabolites and long-term ASCVD risk is not known.

Methods: We characterised the plasma metabolomic profile (1228 metabolites) of 1852 participants (58.

Altering the intracellular trafficking of Necator americanus GST-1 antigen yields novel hookworm mRNA vaccine candidates.

Background: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.

Methodology/findings: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens.

Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.

Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART.