Noncoding variants and sulcal patterns in congenital heart disease: Machine learning to predict functional impact.

Neurodevelopmental impairments associated with congenital heart disease (CHD) may arise from perturbations in brain developmental pathways, including the formation of sulcal patterns. While genetic factors contribute to sulcal features, the association of noncoding variants (ncDNVs) with sulcal patterns in people with CHD remains poorly understood. Leveraging deep learning models, we examined the predicted impact of ncDNVs on gene regulatory signals.

Mastering rectal cancer MRI: From foundational concepts to optimal staging.

MRI plays a critical role in the local staging, restaging, surveillance, and risk stratification of patients, ensuring they receive the most tailored therapy. As such, radiologists must be familiar not only with the key MRI findings that influence management decisions but also with the appropriate MRI protocols and structured reporting. Given the complexity of selecting the optimal therapy for each patient-which often requires multidisciplinary discussions-radiologists should be well-versed in relevant treatment strategies and surgical terms, understanding their significance in guiding patient care.

Systematic ocular phenotyping of 8,707 knockout mouse lines identifies genes associated with abnormal corneal phenotypes.

Purpose: Corneal dysmorphologies (CDs) are typically classified as either regressive degenerative corneal dystrophies (CDtrs) or defective growth and differentiation-driven corneal dysplasias (CDyps). Both eye disorders have multifactorial etiologies. While previous work has elucidated many aspects of CDs, such as presenting symptoms, epidemiology, and pathophysiology, the genetic mechanisms remain incompletely understood.

D dopamine / mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression, and a conditioned place preference procedure: assessment of therapeutic index in male Sprague Dawley rats.

Rationale And Objectives: In vivo receptor interactions vary as a function of behavioral endpoint, with key differences between reflexive and non-reflexive measures that assess the motivational aspects of pain and pain relief. There have been no assessments of D dopamine agonist / mu opioid receptor (MOR) agonist interactions in non-reflexive behavioral measures of pain. We examined the hypothesis that D/MOR mixtures show enhanced effectiveness in blocking pain depressed behaviors while showing decreased side effects such as sedation and drug reward.

Microbial biogeography along a 2578 km transect on the East Antarctic Plateau.

Microorganisms are present in snow/ice of the Antarctic Plateau, but their biogeography and metabolic state under extreme local conditions are poorly understood. Here, we show the diversity and distribution of microorganisms in air (1.5 m height) and snow/ice down to 4 m depth at three distant latitudes along a 2578 km transect on the East Antarctic Plateau on board an environmentally friendly, mobile platform.

Folic Acid and Methyltetrahydrofolate Supplementation in the Mouse Model with Hepatic Steatosis.

Background/objectives: The gene variant results in a thermolabile MTHFR enzyme associated with elevated plasma homocysteine in TT individuals. Health risks associated with the TT genotype may be modified by dietary and supplemental folate intake. Supplementation with methyltetrahydrofolate (methylTHF) may be preferable to folic acid because it is the MTHFR product, and does not require reduction by DHFR to enter one-carbon folate metabolism.

[Management of a fetus suspected of differences of sex development (DSD).].

The management of a fetus suspected of having a variation in genital development is a complex situation. In cases of complete discordance or an unusual appearance of the external genitalia (EG), management always begins with a diagnostic morphological ultrasound. This ultrasound aims to provide detailed imaging of the EG and internal genitalia (IG), focusing on identifying the presence of Müllerian derivatives and detecting any associated malformations.

Brief Report: Genital Microbiome, Inflammation, and Tenofovir Levels in Transgender Men and Cisgender Women Taking Oral PrEP.

Background: Little is known about the efficacy of preexposure prophylaxis (PrEP) or what biologic factors may influence HIV transmission in transgender men (TGM). In this study, we sought to explore the effect of testosterone on the vaginal microbiome, cervicovaginal fluid (CVF) tenofovir concentrations, and levels of CVF inflammatory markers in TGM on PrEP.

Methods: Cervicovaginal fluid was collected from 13 TGM (7 using testosterone) and 32 cisgender women (CGW) on PrEP.

Dietary caloric input and tumor growth accelerate senescence and modulate liver and adipose tissue crosstalk.

Metabolic alterations are related to tumorigenesis and other age-related diseases that are accelerated by "Westernized" diets. In fact, hypercaloric nutrition is associated with an increased incidence of cancers and faster aging. Conversely, lifespan-extending strategies, such as caloric restriction, impose beneficial effects on both processes.

The Anti-AGEing and RAGEing Potential of Isothiocyanates.

Isothiocyanates (ITCs), found in edible plants such as cruciferous vegetables, are a group of reactive organo-sulfur phytochemicals produced by the hydrolysis of precursors known as glucosinolates. ITCs have been studied extensively both in vivo and in vitro to define their therapeutic potential for the treatment of chronic health conditions. Therapeutically, they have shown an intrinsic ability to inhibit oxidative and inflammatory phenotypes to support enhanced health.

Drivers of Seasonal Change of Avian Communities in Urban Parks and Cemeteries of Latin America.

Urban parks and cemeteries constitute hot spots of bird diversity in urban areas. However, the seasonal dynamics of their bird communities have been scarcely explored at large scales. This study aims to analyze the drivers of urban bird assemblage seasonality in urban parks and cemeteries comparing assemblages during breeding and non-breeding seasons in the Neotropical Region.

Evaluation of rheumatoid arthritis-associated interstitial lung disease in patients treated with JAK inhibitors: a MAJIK-SFR cohort study.

Objective: To examine the course of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) in France on treatment with Janus kinase inhibitors (JAKis) using the MAJIK-SFR registry.

Methods: Prospective national multicentre observational study identifying patients with RA-ILD from the MAJIK-SFR registry. Pulmonary assessment data were collected at JAKi initiation and follow-up visits (6 months, 12 months and a median of 21 months postinclusion), including chest high-resolution CT (HRCT), pulmonary function tests (forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)), acute exacerbations of ILD, respiratory infections and lung cancers.

Primary respiratory support of extremely preterm neonates in the Netherlands: a national survey.

Introduction: Non-invasive respiratory support strategies have evolved to avoid bronchopulmonary dysplasia (BPD) in preterm infants. However, consensus on the best treatment strategy remains lacking. This study aims to investigate current practices and variations in primary respiratory support for extremely preterm neonates across neonatal intensive care units (NICUs) in the Netherlands.

Assessing COVID-19 transmission through school and family networks using population-level registry data from the Netherlands.

Understanding the impact of different types of social interactions is key to improving epidemic models. Here, we use extensive registry data-including PCR test results and population-level networks-to investigate the impact of school, family, and other social contacts on SARS-CoV-2 transmission in the Netherlands (June 2020-October 2021). We isolate and compare different contexts of potential SARS-CoV-2 transmission by matching pairs of students based on their attendance at the same or different primary school (in 2020) and secondary school (in 2021) and their geographic proximity.

Exposure to the Polychlorinated biphenyl mixture Aroclor 1254 elicits neurological and cardiac developmental effects in early life stage zebrafish (Danio rerio).

The goal of this study was to compare the bioaccumulation of the PCB mixture Aroclor 1254 in zebrafish to cardiac and neurologic outcomes. The establishment of effect concentrations (ECs) for cardiac and neurotoxic effects of PCBs in early life stage fish is challenging due to a lack of measured PCB concentrations in test media (e.g.

Consideration of Cybersecurity Risks in the Benefit-Risk Analysis of Medical Devices: Scoping Review.

Background: The integration of connected medical devices (MDs) into health care brings benefits but also introduces new, often challenging-to-assess risks related to cybersecurity, which have the potential to harm patients. Current regulations in the European Union and the United States mandate the consideration of these risks in the benefit-risk analysis (BRA) required for MD approval. This important step in the approval process weighs all the defined benefits of a device with its anticipated risks to ensure that the product provides a positive argument for use.

Individual application patterns of Cannabis-based Medicines in Germany - Descriptive evaluation of a patient survey and discussion from a forensic perspective.

Background: An increasing number of countries have legalised cannabis for medicinal purposes in recent years leading to tensions with other regulatory frameworks. Some countries grant a medical defence according to their drug driving legislations. This may lead to specific medico-legal assessments relating to the participation of cannabis patients in road traffic.

Advanced strategies for intensive care management of acute liver failure.

Acute liver failure (ALF) is defined as the loss of hepatic function in conjunction with hepatic encephalopathy and coagulopathy. There is histological evidence of profound hepatocyte damage. If it is not aggressively managed, ALF can be fatal within a few days.

Count Me In: patient-partnered research to address disparities for rare cancer patients.

Background: Approximately 25% of cancer patients are diagnosed with rare cancers and face unique challenges. Decentralized patient-partnered research efforts, like Count Me In provide an avenue for patients to participate in research that overcomes key barriers to address disparities in rare cancer research to accelerate discovery.

Objectives: Projects in metastatic breast cancer (The Metastatic Breast Cancer Project; MBCproject) and angiosarcoma (The Angiosarcoma Project; ASCproject) highlight disparities that exist for all cancer patients and underscore those that are compounded for rare cancer patients.

The Professional Identity of STEM Faculty as Instructors of Course-based Research Experiences.

The professional identity of scientists has historically been cultivated to value research over teaching, which can undermine initiatives that aim to reform science education. Course-Based Research Experiences (CRE) and the inclusive Research and Education Communities (iREC) are two successful and impactful reform efforts that integrate research and teaching. The aim of this study is to explicate the professional identity of instructors who implement a CRE within an established iREC and to explore how this identity contributes to the success of these programs.

Associations of PFAS concentrations during pregnancy and midlife with bone health in midlife: Cross-sectional and prospective findings from Project Viva.

Background: PFAS may impair bone health, but effects of PFAS exposure assessed during pregnancy and the perimenopause-life stages marked by rapidly changing bone metabolism-on later life bone health are unknown.

Methods: We studied 531 women in the Boston-area Project Viva cohort. We used multivariable linear, generalized additive, and mixture models to examine associations of plasma PFAS concentrations during early pregnancy [median (IQR) maternal age 32.

Repurposing an epithelial sodium channel inhibitor as a therapy for murine and human skin inflammation.

Inflammatory skin disease is characterized by a pathologic interplay between skin cells and immunocytes and can result in disfiguring cutaneous lesions and systemic inflammation. Immunosuppression is commonly used to target the inflammatory component; however, these drugs are often expensive and associated with side effects. To identify previously unidentified targets, we carried out a nonbiased informatics screen to identify drug compounds with an inverse transcriptional signature to keratinocyte inflammatory signals.

Do the hormetic effects of chlorogenic acid mediate some of the beneficial effects of coffee?

The present paper provides the first documentation and assessment of the capacity of chlorogenic acid to induce hormetic dose-response relationships. The findings suggest that chlorogenic acid may induce anabolic (i.e.