Multiscale footprints reveal the organization of cis-regulatory elements.

Cis-regulatory elements (CREs) control gene expression and are dynamic in their structure and function, reflecting changes in the composition of diverse effector proteins over time. However, methods for measuring the organization of effector proteins at CREs across the genome are limited, hampering efforts to connect CRE structure to their function in cell fate and disease. Here we developed PRINT, a computational method that identifies footprints of DNA-protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.

Long-Term Safety of Ixekizumab Treatment in Patients with Psoriasis, Psoriatic Arthritis, or Axial Spondyloarthritis: a Post Hoc Analysis of Cerebro-Cardiovascular Events.

Introduction: Psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) may confer an increased risk for cardiovascular (CV) disease, including major adverse cerebro-cardiovascular events (MACE), deep vein thrombosis (DVT), and pulmonary embolism (PE). Patients with these conditions are often exposed for extended time periods to biologics, such as ixekizumab (IXE). Therefore, understanding the risk of CV events, especially MACE, in patients with PsO, PsA, and axSpA exposed to IXE is important.

The PRO-AGE Tool and Its Association With Post Discharge Outcomes in Older Adults Admitted From the Emergency Department.

Background: Existing risk scores assessing geriatric vulnerability in the emergency department (ED) have shown limited predictive power, especially in diverse populations. We investigated the relationship of a quick and easy-to-administer geriatric vulnerability scoring system with functional decline and mortality in older patients admitted to multiple hospitals through the ED in the United States (US) and Brazil (BR).

Method: Federated, international, multicenter observational study of hospitalized ED patients aged ≥ 65 from US and BR.

Predictors of failure of percutaneous endoscopic gastrostomy tube placement: a retrospective study in a tertiary care center in the USA.

Background /aims: Percutaneous endoscopic gastrostomy (PEG) tube placement is a common procedure used to initiate enteral feeding. To our knowledge, there are no previous studies that analyze predictors of PEG failure. This study aims to identify risk factors for failure of inpatient PEG placement.

Speak and you shall predict: evidence that speech at initial cocaine abstinence is a biomarker of long-term drug use behavior.

Background: Valid scalable biomarkers for predicting longitudinal clinical outcomes in psychiatric research are crucial for optimizing intervention and prevention efforts. Here we recorded spontaneous speech from initially abstinent individuals with cocaine use disorder (iCUD) for use in predicting drug use outcomes.

Methods: At baseline, 88 iCUD provided 5-minute speech samples describing the positive consequences of quitting drug use and negative consequences of using drugs.

Diagnosis of atrial cardiomyopathy: from the electrocardiogram to the new opportunities with multimodality imaging.

Atrial cardiomyopathy (AC) has been defined by the European Heart Rhythm Association as "Any complex of structural, architectural, contractile, or electrophysiologic changes in the atria with the potential to produce clinically relevant manifestations".1 The left atrium (LA) plays a key role in maintaining normal cardiac function; in fact atrial dysfunction has emerged as an essential determinant of outcomes in different clinical scenarios, such as valvular diseases, heart failure (HF), coronary artery disease (CAD) and atrial fibrillation (AF). A comprehensive evaluation, both anatomical and functional, is routinely performed in cardiac imaging laboratories.

Red Breast Syndrome-Where Has It Gone?: A Systematic Review of Red Breast Syndrome Incidence Overtime.

Background: Red breast syndrome (RBS) has been noted in past literature as a possible complication of implant-based breast reconstruction (IBBR) with the use of acellular dermal matrices (ADMs). Since its first appearance in 2009, RBS has drawn growing medical attention with reported incidence ranging from 7%-9%. There has been a noted decrease in the emergence of RBS despite its inclusion among the analyzed complications in a number of studies.

Cardiac allograft tolerance can be achieved in nonhuman primates by donor bone marrow and kidney cotransplantation.

Long-term, immunosuppression-free allograft survival has been induced in human and nonhuman primate (NHP) kidney recipients after nonmyeloablative conditioning and donor bone marrow transplantation (DBMT), resulting in transient mixed hematopoietic chimerism. However, the same strategy has consistently failed in NHP heart transplant recipients. Here, we investigated whether long-term heart allograft survival could be achieved by cotransplanting kidneys from the same donor.

A pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies.

Orthohantaviruses are emerging zoonotic viruses that can infect humans via the respiratory tract. There is an unmet need for an in vivo model to study infection of different orthohantaviruses in physiologically relevant tissue and to assess the efficacy of novel pan-orthohantavirus countermeasures. Here, we describe the use of a human lung xenograft mouse model to study the permissiveness for different orthohantavirus species and to assess its utility for preclinical testing of therapeutics.

Sex Differences in Long COVID.

Importance: A substantial number of individuals worldwide experience long COVID, or post-COVID condition. Other postviral and autoimmune conditions have a female predominance, but whether the same is true for long COVID, especially within different subgroups, is uncertain.

Objective: To evaluate sex differences in the risk of developing long COVID among adults with SARS-CoV-2 infection.

Factors Associated with Corneal Hysteresis in an Elderly White Population: The Thessaloniki Eye Study.

Prcis: In 801 participants, corneal hysteresis (CH) was positively associated with female gender and central corneal thickness, and negatively with age and axial length. Diabetes showed no significant association with CH in the adjusted models.

Purpose: To provide values of corneal hysteresis (CH) in an elderly, healthy Greek population and to investigate its association with demographic, ocular, and systemic factors.

Immunogenicity of the 9-valent human papillomavirus vaccine: Post hoc analysis from five phase 3 studies.

Post hoc analyses of 9-valent human papillomavirus (9vHPV) vaccine immunogenicity were conducted in five Phase 3 studies that enrolled males. Month 7 antibody geometric mean titers (GMTs) after three 9vHPV vaccine doses were analyzed in 10,024 males/females aged 16-26 years from studies 001 (NCT00543543), 002 (NCT00943722), 003 (NCT01651949), and 020 (NCT02114385). Covariates considered were age, gender, sexual orientation, region of residence, and race.

Digital phenotyping of social functioning and employment in people with schizophrenia: Pilot data from an international sample.

Aim: Individuals living with schizophrenia experience significant impairments in social functioning. As a major clinical outcome, social functioning requires appropriate measurement tools that can capture its dynamic nature. Digital phenotyping, using smartphone technology to collect high volume ecologically valid data, can potentially capture these facets.

Impact of cell plasticity on prostate tumor heterogeneity and therapeutic response.

Epithelial-mesenchymal transition (EMT) is a dynamic process of lineage plasticity in which epithelial cancer cells acquire mesenchymal traits, enabling them to metastasize to distant organs. This review explores the current understanding of how lineage plasticity and phenotypic reprogramming drive prostate cancer progression to lethal stages, contribute to therapeutic resistance, and highlight strategies to overcome the EMT phenotype within the prostate tumor microenvironment (TME). Emerging evidence reveals that prostate tumor cells can undergo lineage switching, adopting alternative growth pathways in response to anti-androgen therapies and taxane-based chemotherapy.

VHA Support for Home Health Agency Staff and Patients During Natural Disasters.

Background: Home health agencies (HHAs) provide vital community-based services for older adults. Under-resourced HHAs that are disconnected from broader community emergency planning efforts may struggle to maintain services during emergencies. As climate-related disasters become more prevalent, HHA services are increasingly at risk, and policymakers have focused on the services they provide to older adults.

Pulse Irrigation Reduces Rate of Postoperative Hematoma Following Breast Reduction.

Purpose: Breast reduction (BR) involves a large surface area of manipulated tissue, increasing the risk of postoperative hematoma. Pulse irrigation (PI) uses a device to deliver intermittent pressurized irrigant intraoperatively. This study aims to evaluate whether the use of PI is associated with reduced incidence of postoperative hematoma after BR.

Neuroeconomically dissociable forms of mental accounting are altered in a mouse model of diabetes.

Those with diabetes mellitus are at high-risk of developing psychiatric disorders, especially mood disorders, yet the link between hyperglycemia and altered motivation has not been thoroughly explored. Here, we characterized value-based decision-making behavior of a streptozocin-induced diabetic mouse model on Restaurant Row, a naturalistic neuroeconomic foraging paradigm capable of behaviorally capturing multiple decision systems known to depend on dissociable neural circuits. Mice made self-paced choices on a daily limited time-budget, accepting or rejecting reward offers based on cost (delays cued by tone pitch) and subjective value (flavors), in a closed-economy system tested across months.

Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer.

Maturation of conventional dendritic cells (cDCs) is crucial for maintaining tolerogenic safeguards against auto-immunity and for promoting immunogenic responses to pathogens and cancer. The subcellular mechanism for cDC maturation remains poorly defined. We show that cDCs mature by leveraging an internal reservoir of cholesterol (harnessed from extracellular cell debris and generated by de novo synthesis) to assemble lipid nanodomains on cell surfaces of maturing cDCs, enhance expression of maturation markers and stabilize immune receptor signaling.

Low Dose Tamoxifen for Breast Cancer Prevention: A Real-World Experience.

Purpose: There is limited data on the use of low dose tamoxifen (LDT) for chemoprevention since its introduction in 2019. This study sought to determine the rate of LDT uptake at our institution and describe factors associated with its use.

Methods: We performed a retrospective chart review of women diagnosed with ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), and/or atypical hyperplasia from 2019 to 2021.

Evaluation of AI-based auto-contouring tools in radiotherapy: A single-institution study.

Background: Accurate delineation of organs at risk (OARs) is crucial yet time-consuming in the radiotherapy treatment planning workflow. Modern artificial intelligence (AI) technologies had made automation of OAR contouring feasible. This report details a single institution's experience in evaluating two commercial auto-contouring software tools and making well-informed decisions about their clinical adoption.

Computed tomography coronary angiography as an alternative to invasive coronary angiography in preoperative evaluation for mitral surgery.

Objective: The aim of this study was to assess the effectiveness of non-invasive coronary computed tomography angiography (CTA) as an alternative to traditional invasive coronary angiography (ICA) for preoperative evaluation of low risk patients with an indication for non-emergent mitral surgery and to assess any difference in adverse outcomes from this strategy.

Methods: This was a retrospective cohort study from a single center with data collected from July 2014 - June 2020 for 1576 patients undergoing mitral valve surgery of all etiologies - excluding patients requiring coronary artery bypass surgery. We performed a 1:2 propensity score matching for patients evaluated with CT (n=345) to those evaluated with ICA (n=602).