K currents in ventricular cardiomyocytes of p.N98S-calmodulin mutant mice.

Missense mutations in calmodulin (CaM)-encoding genes are associated with life-threatening ventricular arrhythmia syndromes. Here, we investigated a role of cardiac K channel dysregulation in arrhythmogenic long QT syndrome (LQTS) using a knock-in mouse model heterozygous for a recurrent mutation (p.N98S) in the gene (Calm1).

Racial and Ethnic Differences in Prostate Cancer Epidemiology Across Disease States in the VA.

Importance: Prostate cancer (PC) care has evolved rapidly as a result of changes in prostate-specific antigen testing, novel imaging, and newer treatments. The impact of these changes on PC epidemiology and racial disparities across disease states remains underexplored.

Objective: To characterize racial and ethnic differences in the epidemiology of PC states, including nonmetastatic hormone-sensitive PC (nmHSPC), metastatic HSPC (mHSPC), nonmetastatic castration-resistant PC (nmCRPC), and metastatic CRPC (mCRPC).

Main versus segmental hepatic artery angioembolization in patients with traumatic liver injuries: A Western Trauma Association multicenter study.

Introduction: Hepatic angioembolization is highly effective for hemorrhage control in hemodynamically stable patients with traumatic liver injuries and contrast extravasation. However, there is a paucity of data regarding the specific location of angioembolization within the hepatic arterial vasculature and its implications on patient outcomes.

Methods: A post-hoc analysis of a multicenter prospective observational study across 23 centers was performed.

ACR Appropriateness Criteria® Altered Mental Status, Coma, Delirium, and Psychosis: 2024 Update.

Altered mental status (AMS) and coma are terms used to describe disorders of arousal and content of consciousness. AMS may account for up to 4% to 10% of chief complaints in the emergency department setting and is a common accompanying symptom for other presentations. AMS is not a diagnosis, but rather a term for symptoms of acute or chronic disordered mentation, including confusion, disorientation, lethargy, drowsiness, somnolence, unresponsiveness, agitation, altered behavior, inattention, hallucinations, delusions, and psychosis.

Clinical correlates of a single-item physical activity questionnaire among patients undergoing stress SPECT myocardial perfusion imaging.

Background: There has been an increasing call for employing ultrashort exercise activity questionnaires as a clinical "vital sign". To-date, this has not been applied to patients undergoing cardiac stress testing.

Methods: We evaluated 1136 patients who completed a one-item exercise questionnaire before undergoing stress SPECT myocardial perfusion imaging (MPI).

Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer.

BACKGROUNDDespite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment.METHODSWe evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared with mid-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.

A Journey through the Minefield of the Discovery and Characterization of Latency-Related RNA/Latency-Associated Transcript.

Scientific knowledge evolves in small steps, with occasional backsteps to correct inaccuracies, all occurring within a competitive environment. This perspective for the first time looks at the history of latency-related RNA (LR-RNA) that was later renamed latency-associated transcript (LAT). At the 1986 International Herpesvirus Workshop (IHW) meeting in Leeds, England, Daniel L Rock and Anthony B Nesburn first reported the discovery of human herpes virus 1 (HSV-1) latency-related (LR) RNA that is antisense to ICP0.

Observation-first versus angioembolization-first approach in stable patients with blunt liver trauma: A WTA multicenter study.

Background: Prior studies evaluating observation versus angioembolization (AE) for blunt liver injuries (BLT) with contrast extravasation (CE) on computed tomography imaging have yielded inconsistent conclusions, primarily due to limitations in single-center and/or retrospective study design. Therefore, this multicenter study aims to compare an observation versus AE-first approach for BLT, hypothesizing decreased liver-related complications (LRCs) with observation.

Methods: We conducted a post hoc analysis of a multicenter, prospective observational study (2019-2021) across 23 centers.

Identification of proteins associated with type 2 diabetes risk in diverse racial and ethnic populations.

Aims/hypothesis: Several studies have reported associations between specific proteins and type 2 diabetes risk in European populations. To better understand the role played by proteins in type 2 diabetes aetiology across diverse populations, we conducted a large proteome-wide association study using genetic instruments across four racial and ethnic groups: African; Asian; Hispanic/Latino; and European.

Methods: Genome and plasma proteome data from the Multi-Ethnic Study of Atherosclerosis (MESA) study involving 182 African, 69 Asian, 284 Hispanic/Latino and 409 European individuals residing in the USA were used to establish protein prediction models by using potentially associated cis- and trans-SNPs.

Presence of CD80 and Absence of LAT in Modulating Cellular Infiltration and HSV-1 Latency.

CD80 is the best-known costimulatory molecule for effective T cell functions. Many different reports have summarized the role of CD80 in HSV-1 and its functions in maintaining adaptive immunity, which is the main player in causing herpes stromal keratitis (HSK). To determine the effects of absence or overexpression of CD80 in HSV-1 infection, we infected CD80 and WT mice with a recombinant HSV-1 expressing murine CD80 (HSV-CD80) in place of the latency associated transcript (LAT).

A Novel Pathway of Platelet Activation in ACS Mediated by LL-37 Immunoglobulin G Autoantibody Immune Complexes.

The cathelicidin antimicrobial peptide LL-37 is a self-antigen in neutrophil extracellular traps that provokes autoantibody responses in autoimmune/autoinflammatory conditions. LL-37 immunoglobulin (Ig) G autoantibody levels were measured in subjects with and without atherosclerotic cardiovascular disease assessed using the coronary artery calcium score, in patients who had a future myocardial infarction and in a cohort of acute coronary syndrome (ACS) patients. LL-37 IgG levels were not associated with coronary artery calcium score, but future myocardial infarction patients had significantly higher LL-37 IgG at baseline.

Real-world evidence for the utility of serum soluble fms-like tyrosine kinase 1/placental growth factor test for routine clinical evaluation of hospitalized women with hypertensive disorders of pregnancy.

Background: An imbalance of the antiangiogenic factor, soluble fms-like tyrosine kinase-1, and proangiogenic factor, placental growth factor, in the circulation is a reliable predictor for the development of preeclampsia with severe features and related adverse outcomes. In 2023, the US Food and Drug Administration approved a serum soluble fms-like tyrosine kinase-1/placental growth factor test at a cutoff of 40 to aid in the risk assessment of women hospitalized for hypertensive disorders of pregnancy for the progression to preeclampsia with severe features between 23 and 35 weeks.

Objective: This study aimed to generate real-world evidence for clinical utility for serum soluble fms-like tyrosine kinase-1/placental growth factor test when made available to clinicians in a timely fashion as an aid in risk stratification of development of preeclampsia with severe features within 2 weeks of testing among hospitalized patients with hypertensive disorders of pregnancy.

Real-World First-Line Maintenance Niraparib Monotherapy Use Following Chemotherapy Plus Bevacizumab: The SW1TCH Study.

Introduction: Clinical trials have demonstrated prolonged survival associated with niraparib first-line maintenance (1LM) therapy, compared with placebo, for patients with ovarian cancer (OC). However, data are limited on real-world 1LM niraparib monotherapy use, particularly as switch 1LM, following first-line (1L) combination chemotherapy plus bevacizumab. This real-world study aimed to describe patient demographics, clinical characteristics, and clinical outcomes of patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab.

Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: a systematic analysis from the global burden of disease study 2019.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary.

The anti-apoptotic function of HSV-1 LAT in neuronal cell cultures but not its function during reactivation correlates with expression of two small non-coding RNAs, sncRNA1&2.

Multiple functions are associated with HSV-1 latency associated transcript (LAT), including establishment of latency, virus reactivation, and antiapoptotic activity. LAT encodes two sncRNAs that are not miRNAs and previously it was shown that they have antiapoptotic activity in vitro. To determine if we can separate the antiapoptotic function of LAT from its latency-reactivation function, we deleted sncRNA1 and sncRNA2 sequences in HSV-1 strain McKrae, creating ΔsncRNA1&2 recombinant virus.

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.

Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).

Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes.

Robotic-Assisted Bronchoscopy for the Diagnosis of Lung Lesions: Experience With the Use of Frozen Sections as an Aid to Confirm the Localization of Lesions During the Procedure.

Context.—: Robotic-assisted navigation bronchoscopy (R-ANB) is used to target peripheral pulmonary nodules that are difficult to biopsy using conventional approaches. Frozen sections are requested to confirm these lesions have been localized and/or to diagnose neoplasms that can be immediately resected.

Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study.

Background: Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes.

Methods: In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included.

An Abdominal Seat Belt Sign is Associated With Similar Incidence of Hollow Viscus Injury but Increased In-Hospital Mortality in Older Adult Trauma Patients: A PCSA Multicenter Study.

Background: The abdominal seat belt sign (SBS) is associated with an increased risk of hollow viscus injury (HVI). Older age is associated with worse outcomes in trauma patients. Thus, older trauma patients ≥65 years of age (OTPs) may be at an increased risk of HVI with abdominal SBS.