Infectious diseases: Household modeling with missing data.

Over three years since the first identified SARS-CoV-2 case was discovered, the role of adolescents and children in spreading the virus remains unclear. Specifically, estimating the relative susceptibility of a child with respect to an adult is still an open question. In our work, we generalize a well-known household model for modeling infectious diseases, to include missing tests.

The genetic landscape of Lynch syndrome in the Israeli population.

Deciphering the spectrum and founder disease-causing variants (DCVs) in specific populations can shape and facilitate the diagnostic process of Lynch Syndrome (LS). The aim of this report was to comprehensively update on the genetic landscape of LS in the ethnically diverse Israeli-Jewish population. The cohort included 1080 carriers from 588 families; some from underrepresented, understudied Israeli ethnic groups recruited from 8 genetic institutes and high-risk clinics throughout the country.

Comprehensive analysis of constitutional mismatch repair deficiency-associated non-Hodgkin lymphomas in a global cohort.

Background: Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20 years. Limited data exist on CMMRD-associated lymphomas and their outcome.

Potentially Missed Diagnoses in Prenatal Versus Postnatal Exome Sequencing in the Lack of Informative Phenotype: Lessons Learned From a Postnatal Cohort.

Objective: To investigate how many novel pathogenic (P) and likely pathogenic (LP) nonprotein-truncating or noncanonical splicing variants would be classified as variants of unknown significance (VUS) if they were detected in fetuses without abnormalities.

Methods: The study included 156 patients with neurodevelopmental disorders diagnosed through postnatal exome sequencing. Causative P/LP nonprotein-truncating and noncanonical splicing variants were retrospectively reclassified in cases without specific prenatal manifestations, disregarding postnatal symptoms.

Percutaneous Treatment of a Left Ventricular Pseudoaneurysm Post-Aortic Valve Replacement.

Left ventricular outflow tract pseudoaneurysm is rare but serious complication after aortic valve replacement and may occur secondarily to endocarditis, suture dehiscence, or morphologic changes at the aortic annulus. We present a case of successful percutaneous closure of a left ventricular outflow tract pseudoaneurysm using various cardiovascular imaging modalities.

Collagen-Based Bailout Compared to Suture-Mediated Vascular Closure Alone During Transcatheter Aortic Valve Replacement.

Background: Hemostasis for transfemoral transcatheter aortic valve replacement (TAVR) is typically achieved using a suture-mediated vascular closure device (VCD) prior to large-bore sheath insertion (preclosure technique). Recently, the addition of a hybrid closure technique using a preclose technique with the addition of a collagen-plug VCD after sheath removal in cases of failed hemostasis has been utilized.

Methods: Data were collected from the Northwell TAVR registry, including 3 high-volume TAVR centers.

Identifying symptom etiologies using syntactic patterns and large language models.

Differential diagnosis is a crucial aspect of medical practice, as it guides clinicians to accurate diagnoses and effective treatment plans. Traditional resources, such as medical books and services like UpToDate, are constrained by manual curation, potentially missing out on novel or less common findings. This paper introduces and analyzes two novel methods to mine etiologies from scientific literature.

A novel RYR1 pathogenic variant - Common among Libyan Jews and associated with a broad phenotypic spectrum.

Mutated skeletal muscle ryanodine receptor-1 (RYR1) gene is associated with a spectrum of autosomal dominant and recessive RyR1-related disorders with a wide phenotype. This report describes a variable phenotype associated with a previously unreported RYR1 frameshift pathogenic variant, (NM_000540.2) c.

Solanum pennellii (LA5240) backcross inbred lines (BILs) for high resolution mapping in tomato.

Wild species are an invaluable source of new traits for crop improvement. Over the years, the tomato community bred cultivated lines that carry introgressions from different species of the tomato tribe to facilitate trait discovery and mapping. The next phase in such projects is to find the genes that drive the identified phenotypes.

BRCA1/2 mutation carriers vs the general breast cancer population (N = 799,986): 21-gene assay-based molecular characterization.

Purpose: We compared 21-gene recurrence score (RS) distribution and expression of the single-gene/gene groups within this assay between BC patients with pathogenic variants (PV) in BRCA1/2 vs the general 21-gene-tested BC population.

Methods: This retrospective study included consecutive 21-gene-tested female ER + HER2-negative BC patients with germline PVs in BRCA1/2. RS/gene expression data were compared to a previously described commercial use database (CDB, N = 799,986).

Contemporary experience of mitral transcatheter edge-to-edge repair technology in patients with mitral annular calcification.

Background: Mitral annular calcification (MAC) has been an exclusion for many of the earlier pivotal trials that were instrumental in gaining device approval and indications for mitral transcatheter edge-to-edge repair (M-TEER).

Aims: To evaluate the impact of MAC on the procedural durability and success of newer generation MitraClip® systems (G3 and G4 systems).

Methods: Data were collected from Northwell TEER registry.

Shortening the Alzheimer's disease assessment scale cognitive subscale.

Background: A short yet reliable cognitive measure is needed that separates treatment and placebo for treatment trials for Alzheimer's disease. Hence, we aimed to shorten the ' (ADAS-Cog) and test its use as an efficacy measure.

Methods: Secondary data analysis of participant-level data from five pivotal clinical trials of donepezil compared with placebo for Alzheimer's disease (N = 2,198).

Central nervous system metastases in breast cancer patients with germline BRCA pathogenic variants compared to non-carriers: a matched-pair analysis.

Background: Breast cancer is a common cause for central nervous system (CNS) metastasis, resulting in a significant reduction in overall survival. Germline pathogenic variants (PVs) in BRCA1/2 are the most common genetic risk factor for breast cancer, associated with poor prognostic factors. This study sought to explore the patterns and outcome of CNS metastases in breast cancer patients with germline PVs in BRCA1/2 genes.

Public health-focused use of COVID-19 rapid antigen and PCR tests.

During the Covid-19 pandemic, accurate PCR tests were augmented by the cheap, rapid, and logistically convenient, yet less sensitive antigen tests. In Israel, a testing policy shift was implemented due to limited availability of PCR tests during the Omicron surge. Thus, both PCR and antigen tests were used, as this was the only alternative for mass testing and surveillance at the time.

The Diagnostic Yield and Implications of Targeted Founder Pathogenic Variant Testing in an Israeli Cohort.

Founder pathogenic variants (PVs) are prevalent in Israel. This study investigated the current practice of offering cancer patients two-step genetic testing, starting with targeted testing for recurring founder PVs, followed, if negative, by next-generation sequencing. A total of 2128 subjects with cancer or a positive family history underwent oncogenetic testing with a panel of 51 recurring PVs at a tertiary medical center in March 2020-January 2023.

Echocardiographic Outcomes With Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients.

Background: The CLASP IID randomized trial (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial) demonstrated the safety and effectiveness of the PASCAL system for mitral transcatheter edge-to-edge repair (M-TEER) in patients at prohibitive surgical risk with significant symptomatic degenerative mitral regurgitation (DMR).

Objectives: This study describes the echocardiographic methods and outcomes from the CLASP IID trial and analyzes baseline variables associated with residual mitral regurgitation (MR) ≤1+.

Methods: An independent echocardiographic core laboratory assessed echocardiographic parameters based on American Society of Echocardiography guidelines focusing on MR mechanism, severity, and feasibility of M-TEER.

Transfemoral tricuspid valve replacement and one-year outcomes: the TRISCEND study.

Background And Aims: For patients with symptomatic, severe tricuspid regurgitation (TR), early results of transcatheter tricuspid valve (TV) intervention studies have shown significant improvements in functional status and quality of life associated with right-heart reverse remodelling. Longer-term follow-up is needed to confirm sustained improvements in these outcomes.

Methods: The prospective, single-arm, multicentre TRISCEND study enrolled 176 patients to evaluate the safety and performance of transcatheter TV replacement in patients with ≥moderate, symptomatic TR despite medical therapy.

Extending the boundaries of cancer therapeutic complexity with literature text mining.

Drug combination therapy is a main pillar of cancer therapy. As the number of possible drug candidates for combinations grows, the development of optimal high complexity combination therapies (involving 4 or more drugs per treatment) such as RCHOP-I and FOLFIRINOX becomes increasingly challenging due to combinatorial explosion. In this paper, we propose a text mining (TM) based tool and workflow for rapid generation of high complexity combination treatments (HCCT) in order to extend the boundaries of complexity in cancer treatments.