Sex-Specific Clinical and Genetic Factors Associated With Adverse Outcomes in Hypertrophic Cardiomyopathy.

Background: Females with hypertrophic cardiomyopathy present at a more advanced stage of the disease and have a higher risk of heart failure and death. The factors behind these differences are unclear. We aimed to investigate sex-related differences in clinical and genetic factors affecting adverse outcomes in the Sarcomeric Human Cardiomyopathy Registry.

Mineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification.

Background: Vascular calcification is a detrimental aging pathology markedly accelerated in patients with chronic kidney disease. Prelamin A is a biomarker of vascular smooth muscle cell aging that accelerates calcification however the mechanisms remain undefined.

Methods: Vascular smooth muscle cells were transduced with prelamin A using an adenoviral vector and epigenetic modifications were monitored using immunofluorescence and targeted polymerase chain reaction array.

Fundus Curvature as a Clinical Marker for Posterior Staphyloma Based on Widefield Optical Coherence Tomography.

Purpose: To investigate the ability to quantify fundus curvature and detect posterior staphyloma using widefield optical coherence tomography (OCT).

Design: Cross-sectional diagnostic evaluation.

Methods: This study reviewed 205 highly myopic eyes of 205 participants.

Perfusion Showdown: Comparison of Multiple MRI Perfusion Techniques in the Grading of Pediatric Brain Tumors.

Background And Purpose: There are multiple MRI perfusion techniques, with limited available literature comparing these techniques in the grading of pediatric brain tumors. For efficiency and limiting scan time, ideally only one MRI perfusion technique can be used in initial imaging. We compared DSC, DCE, and IVIM along with ADC from DWI for differentiating high versus low grade pediatric brain tumors.

mRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting.

We investigated mRNA vaccines encoding a membrane-anchored receptor-binding domain (RBD), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail fragments of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In naive mice, RBD-TM mRNA vaccines against SARS-CoV-2 variants induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays revealed broad neutralizing activity against a range of variant RBDs.

Protein Biomarkers of Adverse Clinical Features and Events in Sarcomeric Hypertrophic Cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is a heterogeneous condition that can lead to atrial fibrillation, heart failure, and sudden cardiac death in many individuals but mild clinical impact in others. The mechanisms underlying this phenotypic heterogeneity are not well defined. The aim of this study was to use plasma proteomic profiling to help illuminate biomarkers that reflect or inform the heterogeneity observed in HCM.

Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.

Background: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being.

Methods: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied.

Incidence and Outcomes of Cardiocerebral Infarction: A Cohort Study of 2 National Population-Based Registries.

Background: Cardiocerebral infarction (CCI), which is concomitant with acute myocardial infarction (AMI) and acute ischemic stroke (AIS), is a rare but severe presentation. However, there are few data on CCI, and the treatment options are uncertain. We investigated the characteristics and outcomes of CCI compared with AMI or AIS alone.

Development of Myelin Growth Charts of the White Matter Using T1 Relaxometry.

Background And Purpose: Myelin maturation occurs in late fetal life to early adulthood, with the most rapid changes observed in the first few years of infancy. To quantify the degree of myelination, a specific MR imaging sequence is required to measure the changes in tissue proton relaxivity (R1). R1 positively correlates with the degree of myelination maturation at a given age.

Phenotypic Spectrum of Subclinical Sarcomere-Related Hypertrophic Cardiomyopathy and Transition to Overt Disease.

Genetic hypertrophic cardiomyopathy (HCM) is classically caused by pathogenic/likely pathogenic variants in sarcomere genes (G+). Currently, HCM is diagnosed if there is unexplained left ventricular (LV) hypertrophy with LV wall thickness ≥15 mm in probands or ≥13 mm in at-risk relatives. Although LV hypertrophy is a key feature, this binary metric does not encompass the full constellation of phenotypic features, particularly in the subclinical stage of the disease.

Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention.

Methods: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore.

Antitumor Activity of a Novel LAIR1 Antagonist in Combination with Anti-PD1 to Treat Collagen-Rich Solid Tumors.

We recently reported that resistance to PD-1 blockade in a refractory lung cancer-derived model involved increased collagen deposition and the collagen-binding inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1). Thus, we hypothesized that LAIR1 and collagen cooperated to suppress therapeutic response. In this study, we report that LAIR1 is associated with tumor stroma and is highly expressed by intratumoral myeloid cells in both human tumors and mouse models of cancer.

Combining a wireless radar sleep monitoring device with deep machine learning techniques to assess obstructive sleep apnea severity.

Study Objectives: The gold standard for diagnosing obstructive sleep apnea (OSA) is polysomnography (PSG). However, PSG is a time-consuming method with clinical limitations. This study aimed to create a wireless radar framework to screen the likelihood of 2 levels of OSA severity (ie, moderate-to-severe and severe OSA) in accordance with clinical practice standards.

Reciprocal inhibition between TP63 and STAT1 regulates anti-tumor immune response through interferon-γ signaling in squamous cancer.

Squamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common.

UB-612 pan-SARS-CoV-2 T cell immunity-promoting vaccine protects against COVID-19 moderate-severe disease.

UB-612 pan-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine targets the monomeric Spike S1-receptor binding domain (RBD) subunit protein along with five sequence-conserved T cell epitopes found on Spike S2 and non-Spike M and N proteins. UB-612 vaccination safely induces potent, broad, and long-lasting immunity against SARS-CoV-2. A phase-2 trial-extended observational study during the Omicron BA.

Prognostic Nutritional Index as a Prognostic Factor for Very Early-Stage Hepatocellular Carcinoma.

Introduction: Field factors play more important roles in predicting the outcomes of patients compared with tumor factors in early-stage hepatocellular carcinoma (HCC). However, the prognostic ability of noninvasive serum marker scores for hepatic fibrosis and liver functional reserve on very early-stage HCC is still not yet determined. We aimed to investigate the performance of these serum marker scores in predicting the prognoses of patients with very early-stage HCC.

Safety Assessment and Probiotic Potential Comparison of subsp. BLI-02, LPL28, TYCA06, and ET-66.

subsp. BLI-02, ET-66, LPL28, and TYCA06, isolated from healthy breast milk, miso, and the healthy human gut, were assessed for safety in this study. BLI-02, LPL28, TYCA06, and ET-66 exhibited no antibiotic resistance and mutagenic activity in the Ames test at the highest dosage (5000 μg/plate).

Meta-Analysis of Penetrance and Systematic Review on Transition to Disease in Genetic Hypertrophic Cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease because penetrance (proportion of sarcomere or sarcomere-related P/LP variant carriers who develop disease) is variable, age dependent, and not reliably predicted.

Methods: A systematic search of the literature was performed.