Unraveling the causal impact of smoking and its DNA methylation signatures on cardiovascular disease: Mendelian randomization and colocalization analysis.

Background: To explore the mechanisms linking smoking to cardiovascular diseases (CVDs) from an epigenetic perspective.

Methods: Mendelian Randomization (MR) analysis was performed to assess the causal effects of smoking behavior and DNA methylation levels at smoking-related CpG sites on nine CVDs, including aortic aneurysm, atrial fibrillation, coronary atherosclerosis, coronary heart disease, heart failure, intracerebral hemorrhage, ischemic stroke, myocardial infarction, subarachnoid hemorrhage. Colocalization analysis was used to further identify key smoking-related CpG sites from the MR causal estimates.

Clerkship Students' Use of Clinical Reasoning Concepts After a Pre-clinical Reasoning Course.

Background: Many medical schools have incorporated clinical reasoning (CR) courses into their pre-clinical curricula to address the quality and safety issue of diagnostic error. It is unknown how students use concepts and practices from pre-clinical CR courses once in clerkships.

Objective: We sought to understand how students utilize CR concepts from a pre-clinical course during clerkships and to identify facilitators and barriers to the use of reasoning concepts.

Abdominoplasty Under Total Intravenous Anesthesia Significantly Decreases Deep Venous Thrombosis and Pulmonary Embolism Risk.

Background: Venous thromboembolism (VTE) is the most feared complications of abdominoplasty, and multiple studies in the plastic surgery literature have sought to prevent these complications. General inhalational anesthesia can increase the risk of VTE via a variety of mechanisms. This study evaluates whether performing abdominoplasties under total intravenous anesthesia (TIVA) instead of general inhalational anesthesia can reduce the risk of VTE.

Meta-EA: a gene-specific combination of available computational tools for predicting missense variant effects.

Computational methods for estimating missense variant impact suffer from inconsistent performance across genes, which poses a major challenge for their reliable use in clinical practice. While ensemble scores leverage multiple prediction methods to enhance consistency, the overrepresentation of certain genes in the training data can bias their outcomes. To address this critical limitation, we propose a gene-specific ensemble framework trained on reference computational annotations rather than on clinical or experimental data.

Modified Approach to Segmental Maxillary Surgery: Midline Osteotomy and Parasagittal Soft Tissue Incisions.

Traditional surgical techniques for segmental maxillary surgery include a combination of interdental osteotomies with paramidline bony cuts while keeping the palatal soft tissue intact. Besides surgical complexity, segmental maxillary procedures have been associated with higher incidence of relapse and complications. We present our experience with specific hard- and soft-tissue modifications (midline bony osteotomy and reflection of palatal soft tissue with carefully designed incisions) which will allow surgeons to perform larger expansions with a low incidence of complications and decreased relapse.

The Association between All-cause Mortality and Obstructive Sleep Apnea in Adults: A U-Shaped Curve.

Rationale And Objectives: The relationship between Sleep Apnea (SA) and mortality remains a topic of debate. We explored the relationship between the severity of SA and mortality and the effect of age on this association.

Methods: Using a Veterans' database, we extracted the apnea-hypopnea index (AHI) from physician interpretation of sleep studies, by developing a Natural Language Processing (NLP) pipeline (with 944 manually annotated notes) which achieved more than 85% accuracy.

Cardiovascular Disease and Breast Cancer Stage at Diagnosis.

Importance: Cardiovascular disease (CVD) and cancer are the leading causes of mortality in the US. Large-scale population-based and mechanistic studies support a direct effect of CVD on accelerated tumor growth and spread, specifically in breast cancer.

Objective: To assess whether individuals presenting with advanced breast cancers are more likely to have prevalent CVD compared with those with early-stage breast cancers at the time of diagnosis.

Psychometric evaluation of the Yale-Brown Obsessive-Compulsive Scale in pregnant women.

Purpose: Although many women experience obsessive-compulsive symptoms during the perinatal period, the Yale-Brown Obsessive Compulsive Scale (YBOCS) has not yet been psychometrically evaluated in this population. This study examined the internal consistency, convergent and divergent validity, and factor structure of the YBOCS among pregnant women.

Methods: 256 Women who were 20 to 24 weeks pregnant completed the clinician-administered YBOCS and Mini International Neuropsychiatric Interview (MINI) along with a series of self-report questionnaires including the Edinburgh Postnatal Depression Scale (EPDS), Perinatal Anxiety Screening Scale (PASS) and Obsessive-Compulsive Inventory-Revised (OCI-R).

Rise in Minimally Invasive Surgery for Colorectal Cancer Is Associated With Adoption of Robotic Surgery.

Background: Minimally invasive surgery is associated with improved short-term outcomes and similar long-term oncologic outcomes for colorectal cancer patients compared with open surgery. Although the robotic approach has ergonomic and technical benefits, how it has impacted utilization of traditional laparoscopic surgery and minimally invasive surgery overall is unclear.

Objective: Describe trends in open, robotic, and laparoscopic approaches for colorectal cancer resections and examine factors associated with minimally invasive surgery.

ATRX silences Cartpt expression in osteoblastic cells during skeletal development.

ATP-dependent chromatin remodeling protein ATRX is an essential regulator involved in maintenance of DNA structure and chromatin state and regulation of gene expression during development. ATRX was originally identified as the monogenic cause of X-linked α-thalassemia mental retardation (ATR-X) syndrome. Affected individuals display a variety of developmental abnormalities and skeletal deformities.

The effect of a provisional diagnosis on intern diagnostic reasoning: a mixed methods study.

Objectives: Competency in diagnostic reasoning is integral to medical training and patient safety. Situativity theory highlights the importance of contextual factors on learning and performance, such as being informed of a provisional diagnosis prior to a patient encounter. This study aims to determine how being informed of a provisional diagnosis affects an intern's approach to diagnostic reasoning.

Engraft: A Collaborative Learning Health Network for Enhanced Transplant and Cellular Therapy Outcomes.

The Engraft Learning Health Network (LHN) aims to improve outcomes for patients undergoing transplant and cellular therapy (TCT) through a collaborative, data-driven approach. Engraft brings together diverse stakeholders, including clinicians, patients, caregivers, and institutions, to standardize best practices and accelerate the dissemination of innovations in TCT care. By establishing a multicenter, real-world clinical registry focused on rapid-cycle quality improvement (QI) and implementation research, Engraft seeks to reduce variability in clinical practice to improve TCT outcomes across centers.

Subsequent pregnancies in the IMPAACT 2010/VESTED Trial: high rate of adverse outcomes in women living with HIV.

Introduction: Women with HIV (WHIV) have higher risks of adverse pregnancy outcomes, particularly in the absence of antiretroviral treatment(ART), and timing of ART may impact risk.

Methods: In IMPAACT 2010 (VESTED), 643 pregnant WHIV in 9 countries were randomized 1:1:1 to initiate ART: dolutegravir (DTG)+emtricitabine(FTC)/tenofovir alafenamide(TAF); DTG+FTC/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF. We describe adverse pregnancy outcomes in women with a subsequent pregnancy during 50 weeks of postpartum follow-up: spontaneous abortion (<20 weeks), stillbirth (≥20 weeks), preterm delivery (<37 weeks) and small-for-gestational-age (SGA).

SPOCK2 controls the proliferation and function of immature pancreatic β-cells through MMP2.

Human pluripotent stem cell-derived β-cells (SC-β-cells) represent an alternative cell source for transplantation in diabetic patients. Although mitogens could in theory be used to expand β-cells, adult β-cells very rarely replicate. In contrast, newly formed β-cells, including SC-β-cells, display higher proliferative capacity and distinct transcriptional and functional profiles.

Vaccines targeting p53 mutants elicit anti-tumor immunity.

The p53 tumor suppressor is commonly mutated in cancer; however, there are no effective treatments targeting p53 mutants. A DNA vaccine gWIZ-S237G targeting the p53 S237G mutant, which is highly expressed in A20 murine tumor cells, was developed and administered intramuscularly via electroporation, either alone or in combination with PD-1 blockade. The anti-p53-S237G immunization elicited a robust protective response against subcutaneous A20 tumors and facilitated the infiltration of immune cells including CD8 T cells, NK cells, and DCs.

Optimizing time in harness : factors associated with sonographic resolution of developmental dysplasia of the hip during Pavlik treatment.

Aims: The primary aims of this study were to determine the time to sonographic correction of decentred hips during treatment with Pavlik harness for developmental dysplasia of the hip (DDH) and investigate potential risk factors for a delayed response to treatment.

Methods: This was a retrospective cohort study of infants with decentred hips who underwent a comprehensive management protocol with Pavlik harness between 2012 and 2016. Ultrasound assessments were performed at standardized intervals and time to correction from centring of the femoral head was quantified.

Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study.

Background: Vosoritide is a C-type natriuretic peptide analog that addresses an underlying pathway causing reduced bone growth in achondroplasia. Understanding the vosoritide treatment effect requires evaluation over an extended duration and comparison with outcomes in untreated children.

Methods: After completing ≥6 months of a baseline observational growth study and 52 weeks in a double-blind, placebo-controlled study (ClinicalTrials.