The landscape of primary mismatch repair deficient gliomas in children, adolescents, and young adults: a multi-cohort study.

Background: Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0-40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.

Genetics Adviser: The development and usability testing of a new patient digital health application to support clinical genomic testing.

Purpose: Increasing demand for genomic testing coupled with genetics workforce shortages has placed unsustainable pressure on standard models of care. Digital tools can offer improved access, efficiency, and cost savings. We created a patient-facing digital health application to support genomic testing.

Age-related remodeling of the vocal fold extracellular matrix composition, structure, and biomechanics during tissue maturation.

Purpose: The vocal folds (VFs) are among the most mechanically active connective tissues, vibrating between 80 and 250 hz during speech. Overall VF function is determined by the composition and structure of their extracellular matrix (ECM). During tissue maturation, the VFs remodel from a monolayer of collagen fibers to a tri-layered structure, affecting tissue biomechanics.

Gynecologic cancer screening among women with Lynch syndrome: Information and healthcare access needs.

Objectives: Screening recommendations for gynecologic cancers (GC) associated with Lynch syndrome (LS) are diverse. The objectives of this study were to examine among women with LS: 1) psychosocial factors that influence thoughts and choices about GC screening, and 2) information and unmet healthcare access needs when making GC screening decisions.

Methods: This study used a qualitative design.

Opportunistic genomic screening has clinical utility: An interventional cohort study.

Background: Practice is shifting toward genome-first approaches, such as opportunistic screening for secondary findings (SFs). Analysis of SFs could be extended beyond medically actionable results to include non-medically actionable monogenic disease risks, carrier status, pharmacogenomic variants, and risk variants for common complex disease. However, evidence on the clinical utility of returning these results is lacking.

"Should I Let Them Know I Have This?": Multifaceted Genetic Discrimination and Limited Awareness of Legal Protections among Individuals with Hereditary Cancer Syndromes.

Introduction: Hereditary cancer syndromes (HCS), such as hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome (LS), represent approximately 10% of all cancers. Along with medical burdens associated with the genetic risk of developing cancer, many individuals face stigma and discrimination. Genetic discrimination refers to negative treatment, unfair profiling, or harm based on genetic characteristics, manifesting as "felt" stigma (ostracization without discriminatory acts) or "enacted" stigma (experiencing discriminatory acts).

Azithromycin Prevents Subglottic Stenosis in Mice.

Objective: Pediatric subglottic stenosis (SGS) is characterized by subglottic narrowing which occurs when pathological fibroblasts deposit extracellular matrix that reduces airway patency. Recent clinical observations have suggested that azithromycin may have favorable impacts on SGS reduction while treating airway infections; furthermore, our recent work in mice demonstrated that the airway microbiome influences SGS. In this work, we characterize the protective effect of azithromycin as an immunomodulatory and antibacterial therapeutic against subglottic stenosis.

Incidence, Recognition, and Follow-up of Laboratory Evidence of Acute Kidney Injury in Primary Care Practices: Analysis of 93,259 Creatinine Results.

Background: Community-acquired acute kidney injury (CA-acute kidney injury) is under-recognized in the outpatient setting and is associated with adverse outcomes.

Methods: We analyzed the incidence of CA-acute kidney injury in an academic primary care practice and community health center and assessed recognition and follow-up as determined by repeat creatinine measurement (closed-loop). We reviewed 93,259 specimens for 36,593 unique patients from January 1, 2018, through December 31, 2021.

Autistic traits in youth with familial adenomatous polyposis: A Dutch-Canadian case-control study.

This study investigated the neurodevelopmental impact of pathogenic adenomatous polyposis coli (APC) gene variants in patients with familial adenomatous polyposis (FAP), a cancer predisposition syndrome. We hypothesized that certain pathogenic APC variants result in behavioral-cognitive challenges. We compared 66 FAP patients (cases) and 34 unaffected siblings (controls) to explore associations between APC variants and behavioral and cognitive challenges.

Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.

Background: Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.

Methods: In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries.

A Validated Highly Sensitive Microsatellite Instability Assay Accurately Identifies Individuals Harboring Biallelic Germline PMS2 Pathogenic Variants in Constitutional Mismatch Repair Deficiency.

Background: Constitutional mismatch repair deficiency (CMMRD) is a rare and extraordinarily penetrant childhood-onset cancer predisposition syndrome. Genetic diagnosis is often hampered by the identification of mismatch repair (MMR) variants of unknown significance and difficulties in PMS2 analysis, the most frequently mutated gene in CMMRD. We present the validation of a robust functional tool for CMMRD diagnosis and the characterization of microsatellite instability (MSI) patterns in blood and tumors.

Biallelic EPCAM deletions induce tissue-specific DNA repair deficiency and cancer predisposition.

We report a case of Mismatch Repair Deficiency (MMRD) caused by germline homozygous EPCAM deletion leading to tissue-specific loss of MSH2. Through the use of patient-derived cells and organoid technologies, we performed stepwise in vitro differentiation of colonic and brain organoids from reprogrammed EPCAM iPSC derived from patient fibroblasts. Differentiation of iPSC to epithelial-colonic organoids exhibited continuous increased EPCAM expression and hypermethylation of the MSH2 promoter.

Do patients who read visit notes on the patient portal have a higher rate of "loop closure" on diagnostic tests and referrals in primary care? A retrospective cohort study.

Objectives: The 2021 US Cures Act may engage patients to help reduce diagnostic errors/delays. We examined the relationship between patient portal registration with/without note reading and test/referral completion in primary care.

Materials And Methods: Retrospective cohort study of patients with visits from January 1, 2018 to December 31, 2021, and order for (1) colonoscopy, (2) dermatology referral for concerning lesions, or (3) cardiac stress test at 2 academic primary care clinics.

Probing spin waves in CoO nanoparticles for magnonics applications.

The magnetic properties of spinel nanoparticles can be controlled by synthesizing particles of a specific shape and size. The synthesized nanorods, nanodots and cubic nanoparticles have different crystal planes selectively exposed on the surface. The surface effects on the static magnetic properties are well documented, while their influence on spin waves dispersion is still being debated.

Low Rate of Completion of Recommended Tests and Referrals in an Academic Primary Care Practice with Resident Trainees.

Background: A frequent, preventable cause of diagnostic errors involves failure to follow up on diagnostic tests, referrals, and symptoms-termed "failure to close the diagnostic loop." This is particularly challenging in a resident practice where one third of physicians graduate annually, and rates of patient loss due to these transitions may lead to more opportunities for failure to close diagnostic loops. The aim of this study was to determine the prevalence of failure of loop closure in a resident primary care clinic compared to rates in the faculty practice and identify factors contributing to failure.

Completion of Recommended Tests and Referrals in Telehealth vs In-Person Visits.

Importance: Use of telehealth has increased substantially in recent years. However, little is known about whether the likelihood of completing recommended tests and specialty referrals-termed diagnostic loop closure-is associated with visit modality.

Objectives: To examine the prevalence of diagnostic loop closure for tests and referrals ordered at telehealth visits vs in-person visits and identify associated factors.

Completion Rates and Timeliness of Diagnostic Colonoscopies for Rectal Bleeding in Primary Care.

Background: Rectal bleeding is the most common presenting symptom of colorectal cancer, and guidelines recommend timely follow-up, usually with colonoscopy to ensure timely diagnoses of colorectal cancer.

Objective: Identify loop closure rates and vulnerable process points for patients with rectal bleeding.

Design: Retrospective cohort study, using medical record review of patients aged ≥ 40 with index diagnosis of rectal bleeding at 2 primary practices-an urban academic practice and affiliated community health center, between January 1, 2018, and December 31, 2020.

Combined Immunotherapy Improves Outcome for Replication-Repair-Deficient (RRD) High-Grade Glioma Failing Anti-PD-1 Monotherapy: A Report from the International RRD Consortium.

Unlabelled: Immune checkpoint inhibition (ICI) is effective for replication-repair-deficient, high-grade gliomas (RRD-HGG). The clinical/biological impact of immune-directed approaches after failing ICI monotherapy is unknown. We performed an international study on 75 patients treated with anti-PD-1; 20 are progression free (median follow-up, 3.

Amelioration of Subglottic Stenosis by Antimicrobial Peptide Eluting Endotracheal Tubes.

Introduction: Pediatric subglottic stenosis (SGS) results from prolonged intubation where scar tissue leads to airway narrowing that requires invasive surgery. We have recently discovered that modulating the laryngotracheal microbiome can prevent SGS. Herein, we show how our patent-pending antimicrobial peptide-eluting endotracheal tube (AMP-ET) effectively modulates the local airway microbiota resulting in reduced inflammation and stenosis resolution.

Collections of small urban parks consistently support higher species richness but not higher phylogenetic or functional diversity.

When prioritizing regions for conservation protection, decisions are often based on the principle that a single large reserve should support more species than several small reserves of the same total area (SLOSS). This principle remains a central paradigm in conservation planning despite conflicting empirical evidence and methodological concerns. In urban areas where small parks tend to dominate and policies to promote biodiversity are becoming increasingly popular, determining the most appropriate prioritization method is critical.

Hidden cargo: The impact of historical shipping trade on the recent-past and contemporary non-native flora of northeastern United States.

Premise: Understanding establishment and spread of non-native plants is important in the face of a homogenizing global flora. While many studies focus on successful, invasive species, fewer have studied failed plant introductions. Until the early 1900s, large quantities of ship ballast, often containing foreign plant propagules, were deposited in New Jersey (USA).

Urbanisation generates multiple trait syndromes for terrestrial animal taxa worldwide.

Cities can host significant biological diversity. Yet, urbanisation leads to the loss of habitats, species, and functional groups. Understanding how multiple taxa respond to urbanisation globally is essential to promote and conserve biodiversity in cities.

Modulated Fibrosis and Mechanosensing of Fibroblasts by SB525334 in Pediatric Subglottic Stenosis.

Objective: Subglottic stenosis (SGS) may result from prolonged intubation where fibrotic scar tissue narrows the airway. The scar forms by differentiated myofibroblasts secreting excessive extracellular matrix (ECM). TGF-β1 is widely accepted as a regulator of fibrosis; however, it is unclear how biomechanical pathways co-regulate fibrosis.