Drug Development.

Background: The prohibitive costs of drug development for Alzheimer's Disease (AD) emphasize the need for alternative in silico drug repositioning strategies. Graph learning algorithms, capable of learning intrinsic features from complex network structures, can leverage existing databases of biological interactions to improve predictions in drug efficacy. We developed a novel machine learning framework, the PreSiBOGNN, that integrates muti-modal information to predict cognitive improvement at the subject level for precision medicine in AD.

Performance of the High-STEACS Early Rule Out Pathway Using hs-cTnT at 30 Days in a Multisite US Cohort.

Background: The High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome) pathway risk stratifies emergency department patients with possible acute coronary syndrome. This study aims to determine if the High-STEACS hs-cTnT (high-sensitivity cardiac troponin T) pathway can achieve the ≥99% negative predictive value (NPV) safety threshold for 30-day cardiac death or myocardial infarction (CDMI) in a multisite US cohort of patients with and without known coronary artery disease (CAD).

Methods: A secondary analysis of the STOP-CP (High-Sensitivity Cardiac Troponin T [Gen 5 STAT Assay] to Optimize Chest Pain Risk Stratification) cohort, which enrolled adult emergency department patients with possible acute coronary syndrome at 8 US sites (January 25, 2017-September 6, 2018).

Racism and Postpartum Blood Pressure in a Multiethnic Prospective Cohort.

Background: Postpartum hypertension is a key factor in racial-ethnic inequities in maternal mortality. Emerging evidence suggests that experiences of racism, both structural and interpersonal, may contribute to disparities. We examined associations between gendered racial microaggressions (GRMs) during obstetric care with postpartum blood pressure (BP).

Advancing Monogenic Diabetes Research and Clinical Care by Creating a Data Commons: The Precision Diabetes Consortium (PREDICT).

Monogenic diabetes mellitus (MDM) is a group of relatively rare disorders caused by pathogenic variants in key genes that result in hyperglycemia. Lack of identified cases, along with absent data standards, and limited collaboration across institutions have hindered research progress. To address this, the UChicago Monogenic Diabetes Registry (UCMDMR) and UChicago Data for the Common Good (D4CG) created a national consortium of MDM research institutions called the PREcision DIabetes ConsorTium (PREDICT).

Fresh vs. frozen: pregnancy outcomes and treatment efficacy between fresh embryo transfer vs. untested freeze-all cycles.

Objective: To compare pregnancy outcomes after single blastocyst embryo transfer among patients whose first autologous embryo transfer was either a fresh embryo transfer or a frozen embryo transfer (FET) after a freeze-all, in the absence of preimplantation genetic testing for aneuploidy (PGT-A).

Design: A multicenter retrospective cohort analysis.

Setting: National multicenter fertility practice.

Five-year comparison of clinical and echocardiographic outcomes of pure aortic stenosis with pure aortic regurgitation or mixed aortic valve disease in the COMMENCE trial.

Objective: To compare outcomes of aortic valve replacement (AVR) in patients with pure aortic stenosis (Pure AS) and those with pure aortic regurgitation (Pure AR) or mixed AS and AR (MAVD) in the COMMENCE trial.

Methods: Of 689 patients who underwent AVR in the COMMENCE trial, patients with moderate or severe AR with or without AS (Pure AR + MAVD; n = 135) or Pure AS (n = 323) were included. Inverse probability of treatment weighting Kaplan-Meier survival curves were used for time-to-event endpoints, and longitudinal changes in hemodynamics were evaluated using mixed-effects models.

Malnutrition in adult patients treated with venoarterial extracorporeal membrane oxygenation: A descriptive cohort study.

Objective: To evaluate malnutrition and its association with outcomes in adult patients requiring venoarterial (VA) extracorporeal membrane oxygenation (ECMO).

Methods: Patients cannulated for VA ECMO between January 1, 2020, and January 1, 2023, were screened. Patients on ECMO for <48 hours or without a nutritional evaluation were excluded.

Preoperative medication management turnkey order set for nonemergent adult cardiac surgery.

Objective: The management of preoperative medications is an essential component of perioperative care for the cardiac surgical patient. This turnkey order set is part of a series created by the Enhanced Recovery After Surgery Cardiac Society, first presented at the Annual Meeting of The American Association for Thoracic Surgery in 2023. Numerous guidelines and expert consensus documents have been published to provide guidance in preoperative medication management.

Enhanced Recovery After Surgery (ERAS) cardiac turnkey order set for perioperative pain management in cardiac surgery: Proceedings from the American Association for Thoracic Surgery (AATS) ERAS Conclave 2023.

Objective: Optimal perioperative pain management is an essential component of perioperative care for the cardiac surgical patient. This turnkey order set is part of a series created by the Enhanced Recovery After Surgery Cardiac Society, first presented at the Annual Meeting of The American Association for Thoracic Surgery in 2023. Several guidelines and expert consensus documents have been published to provide guidance on pain management and opioid reduction in cardiac surgery.

Adults and Adolescents With Neuroblastoma: An Analysis of the National Cancer Database.

Background And Objectives: Neuroblastoma, the most common extracranial solid tumor in children, is rare in adults. This study compares patient characteristics, disease patterns, and treatments among adults, adolescents, and children with neuroblastoma.

Methods: We queried the National Cancer Database (2004-2019) for neuroblastoma cases.

Phenotypic Expansion: Fetus With Cole-Carpenter Type 2 Presenting With Novel Neonatal Lethal Skeletal Dysplasia.

We report a 28-year-old G2P0 at 24 weeks 5 days who presented for evaluation secondary to suspected skeletal dysplasia in her fetus. Fetal ultrasound imaging demonstrated foreshortened long bones by 9-10 weeks, multiple bowing deformities and fractures, 11 foreshortened paired ribs with fractures, decreased skull mineralization, frontal bossing, enlarged cavum septum pellucidi, and severe fetal growth restriction (< 2%). Findings were concerning for life limiting condition with thoracic circumference < 2.

Better mental health and fewer depressive symptoms are associated with greater psychological resilience after hip fracture.

Background: High psychological resilience is associated with improved functional outcomes for older adults recovering from hip fracture. The objective of this study was to identify factors associated with increased psychological resilience in older women after hip fracture.

Methods: 129 women aged ≥65 years with recent surgically-repaired hip fracture were enrolled in a trial of exercise and testosterone therapy.

Transplantation of a genetically modified porcine heart into a live human.

Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen.

Identification of CT based radiomic biomarkers for progression free survival in head and neck squamous cell carcinoma.

This study addresses the limited noninvasive tools for Head and Neck Squamous Cell Carcinoma (HNSCC) progression-free survival (PFS) prediction by identifying Computed Tomography (CT)-based biomarkers for predicting prognosis. A retrospective analysis was conducted on data from 203 HNSCC patients. An ensemble feature selection involving correlation analysis, univariate survival analysis, best-subset selection, and the LASSO-Cox algorithm was used to select functional features, which were then used to build final Cox Proportional Hazards models (CPH).

CCR5-ligand decorated rilpivirine lipid-based nanoparticles for sustained antiretroviral responses.

Antiretroviral therapy (ART) improves the quality of life for those living with the human immunodeficiency virus type one (HIV-1). However, poor compliance reduces ART effectiveness and leads to immune compromise, viral mutations, and disease co-morbidities. Here we develop a drug formulation in which a lipid-based nanoparticle (LBNP) carrying rilpivirine (RPV) is decorated with the C-C chemokine receptor type 5 (CCR5) targeting peptide.

Blunted Ventral Striatal Reactivity to Social Reward Is Associated with More Severe Motivation and Pleasure Deficits in Psychosis.

Background And Hypothesis: Among individuals living with psychotic disorders, social impairment is common, debilitating, and challenging to treat. While the roots of this impairment are undoubtedly complex, converging lines of evidence suggest that social motivation and pleasure (MAP) deficits play a central role. Yet most neuroimaging studies have focused on monetary rewards, precluding decisive inferences.

Society for Immunotherapy of Cancer: updates and best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) image analysis and data sharing.

Objectives: Multiplex immunohistochemistry and immunofluorescence (mIHC/IF) are emerging technologies that can be used to help define complex immunophenotypes in tissue, quantify immune cell subsets, and assess the spatial arrangement of marker expression. mIHC/IF assays require concerted efforts to optimize and validate the multiplex staining protocols prior to their application on slides. The best practice guidelines for staining and validation of mIHC/IF assays across platforms were previously published by this task force.

Association of Systemic Thromboxane Generation With Risk of Developing Heart Failure.

Background: Systemic thromboxane A generation, which is readily assessed by quantifying thromboxane B metabolites (TXB-M) in the urine, is associated with impaired cardiac performance and mortality in aspirin (ASA) users with heart failure (HF).

Objectives: This study sought to determine the association of urinary TXB-M with the risk of developing HF in individuals without prior history of HF and with normal left ventricular function irrespective of ASA use.

Methods: Urine TXB-M were measured by immunoassay and adjusted to urine concentration and renal function (TXB-M) in 2,611 Framingham Heart Study participants (54.

Updated Appropriate Use Criteria for Amyloid and Tau PET: A Report from the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging Workgroup.

The Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging convened a multidisciplinary workgroup to update appropriate use criteria (AUC) for amyloid positron emission tomography (PET) and to develop AUC for tau PET. The workgroup identified key research questions that guided a systematic literature review on clinical amyloid/tau PET. Building on this review, the workgroup developed 17 clinical scenarios in which amyloid or tau PET may be considered.

HEPATOCYTE GROWTH FACTOR FOR WALKING PERFORMANCE IN PERIPHERAL ARTERY DISEASE.

Introduction: VM202 is a plasmid encoding two isoforms of hepatocyte growth factor (HGF). In preclinical studies, HGF stimulated angiogenesis and muscle regeneration. This preliminary clinical trial tested the hypothesis that VM202 injections in gastrocnemius muscle would improve walking performance in people with mild to moderate and symptomatic lower extremity peripheral artery disease (PAD).

Family Perspectives on Stigma Toward Women Who Use Drugs in Tanzania.

The stigma surrounding drug use adversely affects the health and wellbeing of people who use drugs. With projected increases in drug use in Africa over the next decade, understanding public perceptions of drug use is critical. This study explores perceptions and attitudes toward illicit drug use from the viewpoint of the families of women who use drugs.

Demographic Correlates of Autism: How Do Associations Compare Between Diagnosis and a Quantitative Trait Measure?

Prevalence of autism diagnosis has historically differed by demographic factors. Using data from 8224 participants drawn from the Environmental influences on Child Health Outcomes (ECHO) Program, we examined relationships between demographic factors and parent-reported autism-related traits as captured by the Social Responsiveness Scale (SRS; T score > 65) and compared these to relations with parent-reported clinician diagnosis of ASD, in generalized linear mixed effects regression analyses. Results suggested lower odds of autism diagnosis, but not of SRS T > 65, for non-Hispanic Black children (adjusted odds ratio [OR] = 0.