Biologically-targeted discovery-replication scan identifies G×G interaction in relation to risk of Barrett's esophagus and esophageal adenocarcinoma.

Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196).

Evaluation of Safety and Efficacy of a Single Lorecivivint Injection in Patients with Knee Osteoarthritis: A Multicenter, Observational Extension Trial.

Introduction: Lorecivivint (LOR), a CDC-like kinase/dual-specificity tyrosine kinase (CLK/DYRK) inhibitor thought to modulate inflammatory and Wnt pathways, is being developed as a potential intra-articular knee osteoarthritis (OA) treatment. The objective of this trial was to evaluate long-term safety of LOR within an observational extension of two phase 2 trials.

Methods: This 60-month, observational extension study (NCT02951026) of a 12-month phase 2a trial (NCT02536833) and 6-month phase 2b trial (NCT03122860) was administratively closed after 36 months as data inferences became limited.

Medical & Socioeconomic Risk Factors Associated with Lack of Neurodevelopmental Evaluation Following Neonatal Cardiac Surgery.

Neonates with congenital heart disease (CHD) who undergo cardiopulmonary bypass (CPB) are at high-risk for unfavorable neurodevelopmental (ND) outcomes and are recommended for ND evaluation (NDE); however, poor rates have been reported. We aimed to identify risk factors associated with lack of NDE. This single-center retrospective observational study included neonates < 30 days old who underwent CPB and survived to discharge between 2012 and 2018.

Historical redlining and clustering of present-day breast cancer factors.

Purpose: Historical redlining, a 1930s-era form of residential segregation and proxy of structural racism, has been associated with breast cancer risk, stage, and survival, but research is lacking on how known present-day breast cancer risk factors are related to historical redlining. We aimed to describe the clustering of present-day neighborhood-level breast cancer risk factors with historical redlining and evaluate geographic patterning across the US.

Methods: This ecologic study included US neighborhoods (census tracts) with Home Owners' Loan Corporation (HOLC) grades, defined as having a score in the Historic Redlining Score dataset; 2019 Population Level Analysis and Community EStimates (PLACES) data; and 2014-2016 Environmental Justice Index (EJI) data.

Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.

Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.

Shaping ability of NiTi reciprocating file systems R-motion and waveOne gold in mesial canals of mandibular molars; micro CT study.

The preservation of the original configurations of root canals during endodontic preparation is crucial for treatment success. Nickel-titanium (NiTi) rotary systems have been refined to optimize canal shaping while minimizing iatrogenic errors. This study aimed to evaluate and compare the shaping efficacy of the novel R-Motion (RM) and the established WaveOne Gold (WG) systems using micro-computed tomography (micro-CT).

Insulin signaling regulates R2 retrotransposon expression to orchestrate transgenerational rDNA copy number maintenance.

Preserving a large number of essential yet highly unstable ribosomal DNA (rDNA) repeats is critical for the germline to perpetuate the genome through generations. Spontaneous rDNA loss must be countered by rDNA copy number (CN) expansion. Germline rDNA CN expansion is best understood in Drosophila melanogaster, which relies on unequal sister chromatid exchange (USCE) initiated by DNA breaks at rDNA.

Machine learning models predicting risk of revision or secondary knee injury after anterior cruciate ligament reconstruction demonstrate variable discriminatory and accuracy performance: a systematic review.

Background: To summarize the statistical performance of machine learning in predicting revision, secondary knee injury, or reoperations following anterior cruciate ligament reconstruction (ACLR), and to provide a general overview of the statistical performance of these models.

Methods: Three online databases (PubMed, MEDLINE, EMBASE) were searched from database inception to February 6, 2024, to identify literature on the use of machine learning to predict revision, secondary knee injury (e.g.

Prognostic value of CHA2DS2-VASc score for in-hospital outcomes in patients with Takotsubo syndrome.

Background: There is uncertainty about the use of the CHA2DS2-VASc score to predict clinical events in patients with Takotsubo syndrome (TTS). This study aimed to assess the short-term prognostic role of CHA2DS2-VASc score in this population.

Methods: All admissions with a primary diagnosis of TTS were included using data from the National Inpatient Sample database during 2016-2019.

Textbook outcome in liver surgery for intrahepatic cholangiocarcinoma: defining predictors of an optimal postoperative course using machine learning.

Background: We sought to define textbook outcome in liver surgery (TOLS) for intrahepatic cholangiocarcinoma (ICC) by considering the implications of perioperative outcomes on overall survival (OS).

Methods: Using a multi-institutional database, TOLS for ICC was defined by employing novel machine learning (ML) models to identify perioperative factors most strongly predictive of OS ≥ 12 months. Subsequently, clinicopathologic factors associated with achieving TOLS were investigated.

Nasal Valve Considerations in Mohs Reconstruction.

Airway obstruction is a possible sequela following reconstruction of the nose after Mohs excision of skin cancers. While the principles and goals of tissue replacement after Mohs micrographic surgery are well-established, less attention has been paid to the evaluation of the nasal airway after reconstruction. Reconstructive planning begins with understanding the risk factors associated with the development of nasal valve compromise.

Protein quality control machinery: regulators of condensate architecture and functionality.

Protein quality control (PQC) mechanisms including the ubiquitin (Ub)-proteasome system (UPS), autophagy, and chaperone-mediated refolding are essential to maintain protein homeostasis in cells. Recent studies show that these PQC mechanisms are further modulated by biomolecular condensates that sequester PQC components and compartmentalize reactions. Accumulating evidence points towards the PQC machinery playing a pivotal role in regulating the assembly, disassembly, and viscoelastic properties of several condensates.

The public health risks of counterfeit pills.

Synthetic illicit drugs, such as nitazenes and fentanyls, are becoming commonplace in countries around the world, including in Europe, Australia, and Latin America, which raises concern for overdose crises like those seen in North America. An important dimension of the risk represented by synthetic drugs is the fact that they are increasingly packaged in counterfeit pill form. These pills-often indistinguishable from authentic pharmaceuticals-have substantially widened the scope of populations susceptible to synthetic drug overdose in North America (eg, among adolescents experimenting with pills or tourists from the USA seeking psychoactive medications from pharmacies in Mexico).

DOME: Directional medical embedding vectors from electronic health records.

Motivation: The increasing availability of electronic health record (EHR) systems has created enormous potential for translational research. Recent developments in representation learning techniques have led to effective large-scale representations of EHR concepts along with knowledge graphs that empower downstream EHR studies. However, most existing methods require training with patient-level data, limiting their abilities to expand the training with multi-institutional EHR data.

How is Telehealth Used to Increase Access to Specialty Palliative Care? A Systematic Review.

Context: Specialty palliative care remains inaccessible for many with serious illness, especially in rural areas. Telehealth may be one solution.

Objectives: To describe how telehealth increases access to specialty palliative care, describe facilitators and barriers to its use, and summarize evidence of patient benefits.

Rhinoconjunctivitis Symptoms in Children and Adolescents with Asthma: A Longitudinal Clustering Analysis.

Background: Rhinoconjunctivitis phenotypes are conventionally described based on symptom severity, duration and seasonality and aeroallergen sensitization. It is not known whether these phenotypes fully reflect the patterns of symptoms seen at a population level.

Objective: To identify phenotypes of rhinoconjunctivitis based on symptom intensity and seasonality using an unbiased approach and to compare their characteristics.

Blood-based diagnosis of pediatric tuberculosis: a prospective cohort study in South Africa and Dominican Republic.

Objectives: Pediatric tuberculosis (TB) diagnosis is complicated by challenges in obtaining invasive respiratory specimens that frequently contain few Mycobacterium tuberculosis (Mtb) bacilli. We report the diagnostic performance of an Mtb antigen-derived peptide (MAP-TB) assay and its ability to monitor TB treatment response.

Methods: Study cohorts enrolled children who presented with presumptive TB at two hospitals in South Africa from 2012 to 2017 (157 children aged <13 years) and at community-based clinics in the Dominican Republic from 2019 to 2023 (101 children aged <18 years).

A Guide to Pediatric Antibiotic Allergy Testing: A Report from the United States Drug Allergy Registry.

Pediatric antibiotic labels are common, and unnecessary antibiotic avoidance is associated with negative personal and public health outcomes; as a result, there is an increasing emphasis on the importance of pediatric antibiotic allergy evaluations. Different testing strategies have been advised, including skin testing and challenge testing with varied doses and duration. Established consensus testing protocols are lacking.

Low-dose aspirin use in low-risk nulliparous pregnancies: a systematic review and meta-analysis of randomized controlled trials.

Objective: To assess the efficacy of low-dose aspirin in the prevention of adverse outcomes in low-risk, nulliparous singleton pregnancies.

Data Sources: PubMed, Ovid MEDLINE, Scopus, Cochrane Library, clinicaltrials.gov, and ScienceDirect were searched from their inception to August 5, 2023.

The Trail of axonal protein Synthesis: Origins and current functional Landscapes.

Local protein synthesis (LPS) in axons is now recognized as a physiological process, participating both in the maintenance of axonal function and diverse plastic phenomena. In the last decades of the 20th century, the existence and function of axonal LPS were topics of significant debate. Very early, axonal LPS was thought not to occur at all and was later accepted to play roles only during development or in response to specific conditions.