RELMβ sets the threshold for microbiome-dependent oral tolerance.

Tolerance to dietary antigens is critical for avoiding deleterious type 2 immune responses resulting in food allergy (FA) and anaphylaxis. However, the mechanisms resulting in both the maintenance and failure of tolerance to food antigens are poorly understood. Here we demonstrate that the goblet-cell-derived resistin-like molecule β (RELMβ) is a critical regulator of oral tolerance.

Association of environmental, demographic and clinical parameters with physical activity in children with asthma.

Personal characteristics, unfavorable weather conditions and air pollution have been linked with reduced physical activity in children. However, among children with asthma the effects of these parameters remain unclear. This study objectively quantified the physical activity of children with asthma and evaluated its association with environmental, personal, and clinical parameters.

Joint Physical-Psychosocial Frailty and Risks of All-Cause and Cause-Specific Premature Mortality.

Background: The importance of integrating physical and psychosocial factors in assessing frailty -health outcomes has been increasingly acknowledged, while the related evidence is lacking. We sought to investigate the associations of joint physical-psychosocial frailty with risk of premature mortality and evaluate the relative importance of individual physical and psychosocial factors.

Design: A total of 381,295 participants with no history of cancer or cardiovascular disease (CVD) were recruited from the UK Biobank cohort.

In vivo CRISPR-Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington's disease.

Huntington's disease, one of more than 50 inherited repeat expansion disorders, is a dominantly inherited neurodegenerative disease caused by a CAG expansion in HTT. Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the disease is driven by the CAG length-dependent propensity of the repeat to further expand in the brain. Routes to slowing somatic CAG expansion, therefore, hold promise for disease-modifying therapies.

FABP4 as a therapeutic host target controlling SARS-CoV-2 infection.

Host metabolic fitness is a critical determinant of infectious disease outcomes. Obesity, aging, and other related metabolic disorders are recognized as high-risk disease modifiers for respiratory infections, including coronavirus infections, though the underlying mechanisms remain unknown. Our study highlights fatty acid-binding protein 4 (FABP4), a key regulator of metabolic dysfunction and inflammation, as a modulator of SARS-CoV-2 pathogenesis, correlating strongly with disease severity in COVID-19 patients.

Fabrication of nonplanar tapered fibers to integrate optical and electrical signals for neural interfaces in vivo.

Implantable multifunctional probes have transformed neuroscience research, offering access to multifaceted brain activity that was previously unattainable. Typically, simultaneous access to both optical and electrical signals requires separate probes, while their integration into a single device can result in the emergence of photogenerated electrical artifacts, affecting the quality of high-frequency neural recordings. Among the nontrivial strategies aimed at the realization of an implantable multifunctional interface, the integration of optical and electrical capabilities on a single, minimally invasive, tapered optical fiber probe has been recently demonstrated using fibertrodes.

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

Evaluating pulmonary stenosis and regurgitation impact on cardiac strain and strain rate in a porcine model via magnetic resonance feature tracking.

Background: Pulmonary stenosis (PS) is common in congenital heart disease and an integral finding in Tetralogy of Fallot (TOF). Pulmonary regurgitation (PR) is more commonly found following surgery in repaired TOF. We aimed to evaluate the haemodynamic effects of PS and PR on cardiac physiology in a porcine model using cardiac magnetic resonance-based feature tracking (CMR-FT) deformation imaging.

Enhancing social functioning using multi-user, immersive virtual reality.

Rates of loneliness and other forms of social disconnection have been increasing worldwide. Prior studies have suggested that brief behavioral interventions can teach skills that may improve social functioning and connection but, currently, access to such interventions is limited. One previously untested approach for addressing this gap is to teach these skills using immersive, multi-user virtual reality (VR).

Telomerase RNA structural heterogeneity in living human cells detected by DMS-MaPseq.

Biogenesis of human telomerase requires its RNA subunit (hTR) to fold into a multi-domain architecture that includes the template-pseudoknot (t/PK) and the three-way junction (CR4/5). These hTR domains bind the telomerase reverse transcriptase (hTERT) protein and are essential for telomerase activity. Here, we probe hTR structure in living cells using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and ensemble deconvolution analysis.

Diversity in the medical research ecosystem: a descriptive scientometric analysis of over 49 000 studies and 150 000 authors published in high-impact medical journals between 2007 and 2022.

Objectives: Health research that significantly impacts global clinical practice and policy is often published in high-impact factor (IF) medical journals. These outlets play a pivotal role in the worldwide dissemination of novel medical knowledge. However, researchers identifying as women and those affiliated with institutions in low- and middle-income countries (LMICs) have been largely under-represented in high-IF journals across multiple fields of medicine.

Elucidating hemodynamics and neuro-glio-vascular signaling using rodent fMRI.

Despite extensive functional mapping studies using rodent functional magnetic resonance imaging (fMRI), interpreting the fMRI signals in relation to their neuronal origins remains challenging due to the hemodynamic nature of the response. Ultra high-resolution rodent fMRI, beyond merely enhancing spatial specificity, has revealed vessel-specific hemodynamic responses, highlighting the distinct contributions of intracortical arterioles and venules to fMRI signals. This 'single-vessel' fMRI approach shifts the paradigm of rodent fMRI, enabling its integration with other neuroimaging modalities to investigate neuro-glio-vascular (NGV) signaling underlying a variety of brain dynamics.

Comparative effectiveness of bictegravir versus dolutegravir, raltegravir, and efavirenz-based antiretroviral therapy among treatment-naïve individuals with HIV.

Objective: Bictegravir or dolutegravir based antiretroviral therapy are first-line HIV treatments. However, no trial has recruited enough participants to estimate the most effective treatment, and there is little evidence on the comparative effectiveness of bictegravir and other available antiretrovirals, like efavirenz and raltegravir.

Methods: We emulated a four-arm target trial using country-wide data from Mexico.

Pericardial effusion cytology: malignancy rates, patterns of metastasis, comparison with pericardial window, and genomic correlates.

Introduction: Cytologic evaluation of pericardial fluid is essential for diagnosing malignant pericardial effusions secondary to metastatic disease and for guiding appropriate clinical management; however, large cohort and up-to-date studies on malignancy rates and distribution of primary tumor sites is lacking.

Materials And Methods: A retrospective analysis of pericardial fluid specimens from 2 large academic medical centers over a 10-year period was conducted. Clinical and specimen characteristics were correlated with cytologic diagnoses, and compared with surgical pathology pericardial specimens when available.

Efficacy and empathy of AI chatbots in answering frequently asked questions on oral oncology.

Objectives: Artificial intelligence chatbots have demonstrated feasibility and efficacy in improving health outcomes. In this study, responses from 5 different publicly available AI chatbots-Bing, GPT-3.5, GPT-4, Google Bard, and Claude-to frequently asked questions related to oral cancer were evaluated.

Entrapment of Pulmonary Artery Catheters in Cardiac Surgery: A Structured Literature Review and Analysis of Published Case Reports.

Objectives: This systematic review aims to tabulate and analyze the published literature regarding pulmonary artery catheter (PAC) entrapment during cardiac surgery.

Design: Systematic review.

Setting: Case reports and series.

Gamma and theta/alpha-band oscillations in the electroencephalogram distinguish the content of inner speech.

Inner speech refers to the silent production of language in one's mind. As a purely mental action without obvious physical manifestations, inner speech has been notoriously difficult to quantify. Inner speech is thought to be closely related to overt speech.