Development of a recombinant Ang1 variant with enhanced Tie2 binding and its application to attenuate sepsis in mice.

The angiopoietin (Ang)-Tie axis, critical for endothelial cell function and vascular development, is a promising therapeutic target for treating vascular disorders and inflammatory conditions like sepsis. This study aimed to enhance the binding affinity of recombinant Ang1 variants to the Tie2 and explore their therapeutic potential. Structural insights from the Ang1-Tie2 complex enabled the identification of key residues within the Ang1 receptor binding domain (RBD) critical for Tie2 interaction.

Recurrence Patterns and Management after Pleurectomy Decortication for Pleural Mesothelioma.

Objective: We hypothesize that recurrence following pleurectomy decortication (PD) is primarily local. We explored factors associated with tumor recurrence patterns, disease-free interval (DFI), and post-recurrence survival (PRS).

Summary Background Data: Tumor recurrence is a major barrier for long-term survival after pleural mesothelioma (PM) surgery.

Afferent Projections to the Calca/CGRP-Expressing Parabrachial Neurons in Mice.

The parabrachial nucleus (PB), located in the dorsolateral pons, contains primarily glutamatergic neurons that regulate responses to a variety of interoceptive and cutaneous sensory signals. One lateral PB subpopulation expresses the Calca gene, which codes for the neuropeptide calcitonin gene-related peptide (CGRP). These PB neurons relay signals related to threatening stimuli such as hypercarbia, pain, and nausea, yet their inputs and their neurochemical identity are only partially understood.

Contemporary Administrative Codes to Identify Pulmonary Vein Isolation Procedures for Atrial Fibrillation.

Background: Use of pulmonary vein isolation (PVI) to treat atrial fibrillation continues to increase. Despite great interest in leveraging administrative data for real-world analyses, contemporary procedural codes for identifying PVI have not been evaluated.

Methods And Results: In this observational retrospective cohort study, inpatient PVIs were identified among US Medicare fee-for-service beneficiaries using Current Procedural Terminology (CPT) code 93656 in Carrier Line Files.

Integrating CT-based radiomics and clinical features to better predict the prognosis of acute pancreatitis.

Objectives: To develop and validate the performance of CT-based radiomics models for predicting the prognosis of acute pancreatitis.

Methods: All 344 patients (51 ± 15 years, 171 men) in a first episode of acute pancreatitis (AP) were retrospectively enrolled and randomly divided into training (n = 206), validation (n = 69), and test (n = 69) sets with the ratio of 6:2:2. The patients were dichotomized into good and poor prognosis subgroups based on follow-up CT and clinical data.

Cardiovascular MRI-derived Right Atrial Strain for Improved Risk Stratification in Patients with Severe Aortic Stenosis.

Purpose To assess the prognostic implications of cardiac MRI-derived imaging markers in individuals with severe aortic stenosis (AS). Materials and Methods This prospective study (German Clinical Trials Register, DRKS00024479) enrolled individuals with severe AS who underwent cardiac MRI before transcatheter aortic valve replacement (TAVR) from January 2017 to March 2022. Image analyses included myocardial volumes, cardiac MRI feature tracking-derived left atrial (LA) and right atrial (RA) as well as left ventricular (LV) and right ventricular (RV) strain, myocardial T1 mapping, and late gadolinium enhancement analyses.

Cost-Effectiveness of a Polypill for Cardiovascular Disease Prevention in an Underserved Population.

Importance: The Southern Community Cohort Study (SCCS) Polypill Trial showed that a cardiovascular polypill (a single pill containing a statin and 3 half-standard dose antihypertensive medications) effectively controls cardiovascular disease (CVD) risk factors in a majority Black race and low-income population. The cost-effectiveness of polypill treatment in this population has not been previously studied.

Objective: To determine the cost-effectiveness of the cardiovascular polypill.

Interleukin-1β Drives Disease Progression in Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a genetic form of heart failure that affects 1 in 5000 people globally and is caused by mutations in cardiac desmosomal proteins including , and . Individuals with ACM suffer from ventricular arrhythmias, sudden cardiac death, and heart failure. There are few effective treatments and heart transplantation remains the best option for many affected individuals.

Identifying the Brain Circuits that Regulate Pain-Induced Sleep Disturbances.

Pain therapies that alleviate both pain and sleep disturbances may be the most effective for pain relief, as both chronic pain and sleep loss render the opioidergic system, targeted by opioids, less sensitive and effective for analgesia. Therefore, we first studied the link between sleep disturbances and the activation of nociceptors in two acute pain models. Activation of nociceptors in both acute inflammatory (AIP) and opto-pain models led to sleep loss, decreased sleep spindle density, and increased sleep fragmentation that lasted 3 to 6 hours.

Chaperone-mediated insertion of mitochondrial import receptor TOM70 protects against diet-induced obesity.

Outer mitochondrial membrane (OMM) proteins communicate with the cytosol and other organelles, including the endoplasmic reticulum. This communication is important in thermogenic adipocytes to increase the energy expenditure that controls body temperature and weight. However, the regulatory mechanisms of OMM protein insertion are poorly understood.

Mechanisms of tandem duplication in the cancer genome.

Tandem duplications (TD) are among the most frequent type of structural variant (SV) in the cancer genome. They are characterized by a single breakpoint junction that defines the boundaries and the size of the duplicated segment. Cancer-associated TDs often increase oncogene copy number or disrupt tumor suppressor gene function, and thus have important roles in tumor evolution.

Impact of Anemia on Clinical Outcomes in Atrial Fibrillation Patients on Oral Anticoagulants: A Prognostic Meta-Analysis.

Background: Anemia is frequently observed as a comorbidity in atrial fibrillation (AF), especially in elderly patients and in those on anticoagulation. This has been associated with poor clinical outcomes. We aim to investigate the impact of anemia on clinical outcomes in patients with AF on oral anticoagulation.

AI-assisted human clinical reasoning in the ICU: beyond "to err is human".

Diagnostic errors pose a significant public health challenge, affecting nearly 800,000 Americans annually, with even higher rates globally. In the ICU, these errors are particularly prevalent, leading to substantial morbidity and mortality. The clinical reasoning process aims to reduce diagnostic uncertainty and establish a plausible differential diagnosis but is often hindered by cognitive load, patient complexity, and clinician burnout.

Genetic analysis of psychosis Biotypes: shared Ancestry-adjusted polygenic risk and unique genomic associations.

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis. Two recently developed post hoc ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples.

Age-related TFEB downregulation in proximal tubules causes systemic metabolic disorders and occasional apolipoprotein A4-related amyloidosis.

With the aging of society, the incidence of chronic kidney disease (CKD), a common cause of death, has been increasing. Transcription factor EB (TFEB), the master transcriptional regulator of the autophagy-lysosomal pathway, is regarded as a promising candidate for preventing various age-related diseases. However, whether TFEB in the proximal tubules plays a significant role in elderly CKD patients remains unknown.

Management of diabetic keto-acidosis in adult patients admitted to intensive care unit: an ESICM-endorsed international survey.

Background: Guidelines for diabetic ketoacidosis (DKA) management are limited, resulting in varied practices. This study assessed Intensive Care Unit (ICU) admission criteria, fluid resuscitation, insulin therapy, and metabolic management in adult patients with DKA.

Methods: An international survey of ICU clinicians consisted of 39 items that focused on management of DKA and was endorsed by the European Society of the Intensive Care Medicine.

Genetic Analysis of Psychosis Biotypes: Shared Ancestry-Adjusted Polygenic Risk and Unique Genomic Associations.

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder and bipolar disorder with psychosis. Two recently developed ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples.

Relationship Between Hospital Mortality and Readmission Rates After Transcatheter Aortic Valve Replacement.

Background: There is substantial hospital-level variation in 30-day risk-standardized mortality rate (RSMR) and risk-standardized readmission rate (RSRR) after transcatheter aortic valve replacement (TAVR). However, the relationship between hospital RSMRs and RSRRs has not been well characterized.

Methods: We analyzed data on 141,905 Medicare fee-for-service beneficiaries who underwent TAVR across 512 hospitals between October 1, 2015 and December 31, 2020.

Interest paradigm for early identification of autism spectrum disorder: an analysis from electroencephalography combined with eye tracking.

Introduction: Early identification of Autism Spectrum Disorder (ASD) is critical for effective intervention. Restricted interests (RIs), a subset of repetitive behaviors, are a prominent but underutilized domain for early ASD diagnosis. This study aimed to identify objective biomarkers for ASD by integrating electroencephalography (EEG) and eye-tracking (ET) to analyze toddlers' visual attention and cortical responses to RI versus neutral interest (NI) objects.

Deep Learning-Based Body Composition Analysis for Cancer Patients Using Computed Tomographic Imaging.

Malnutrition is a commonly observed side effect in cancer patients, with a 30-85% worldwide prevalence in this population. Existing malnutrition screening tools miss ~ 20% of at-risk patients at initial screening and do not capture the abnormal body composition phenotype. Meanwhile, the gold-standard clinical criteria to diagnose malnutrition use changes in body composition as key parameters, particularly body fat and skeletal muscle mass loss.

Clinicopathological features and prognosis of alpha-fetoprotein-producing colorectal adenocarcinoma.

Aims: Alpha-fetoprotein (AFP)-producing colorectal adenocarcinoma (AFPCRA) is uncommon, with obscure clinicopathological features and prognosis.

Methods And Results: In this retrospective comparison study on surgically resected colorectal adenocarcinomas (CRA, n = 2389), we investigated and compared clinicopathological and prognostic features between AFPCRA cases with elevated pre-operative serum AFP levels, as the AFPCRA study group (n = 49, 2.1%), and the exact sex-, age- and stage-matched CRA cases as the control group at a 1:2 ratio during the study period from 2011 to 2021.