How Polyproline Type II Conformation at P Residues Influences the Success of Proline-Based Peptidyl Inhibitors Against Coronavirus Main Protease.

In the wake of the pandemic, peptidyl protease inhibitors with Pro-based rigid Leu mimetics at the P position have emerged as potent drug candidates against the SARS-CoV-2 main protease. This success is intuitively attributed to the enhanced hydrophobic interactions and rigidity of Pro-based rigid Leu mimetics in the literature. However, the tertiary amide of proline P derivatives, which hinders the formation of a critical hydrogen bond with the enzyme active site, and the constrained PP conformation, which contradicts the protease preferred β-strand conformation, represent two overlooked disadvantages associated with these inhibitors over traditional inhibitors and, theoretically, should adversely affect their potency.

Experiences of sexual and reproductive health screening and counseling in the clinical setting among adolescents and young adults with rheumatic disease.

Background: Our objective was to describe differences among adolescents and young adults (AYAs) with rheumatic disease using teratogens compared to non-users in receipt of sexual and reproductive health (SRH) counseling, teratogenicity knowledge, perceived importance of SRH topics, and preferences around counseling.

Methods: AYAs ages 14-23 years and assigned female at birth were recruited from pediatric rheumatology clinics at a Midwest tertiary care program. Participants completed a one-time online survey assessing SRH.

CPT® Codes for MRI Safety - A User's Guide.

The magnetic fields of the MR environment present unique safety challenges. Medical implants and retained foreign bodies can prevent patients from undergoing MR imaging due to interactions between the magnetic fields of the MR environment and the implant or foreign body. These hazards can be addressed through careful MR safety screening and MR examination customization, often allowing these patients with implants to undergo management-altering MR imaging.

Evaluating Young Children With Fractures for Child Abuse: Clinical Report.

Fractures are common injuries in childhood and can be caused by unintentional injury, medical conditions, and child abuse. Although the consequences of failing to diagnose an abusive injury in a child can be grave, the consequences of incorrectly diagnosing child abuse in a child whose fractures have another etiology are also significant. This report aims to review recent advances in the understanding of fracture specificity, fracture mechanisms, and other medical conditions that predispose infants and children to fracture.

Hypusinated and unhypusinated isoforms of the translation factor eIF5A exert distinct effects in models of pancreas development and function.

Hypusination of eukaryotic translation initiation factor 5A (eIF5A) is essential for its role in translation elongation and termination. Although the function of hypusinated eIF5A (eIF5A) in cellular proliferation is well-characterized, the role of its unhypusinated form (eIF5A) remains unclear. We hypothesized that eIF5A exerts independent, negative effects on cellular replication and metabolism, distinct from the loss of eIF5A.

The Association of Jumbo Femoral Heads and Acetabular Cup Position on Patient Outcomes after Modern Posterior Approach Total Hip Arthroplasty.

Background: Use of jumbo femoral heads (≥ 40 mm) in total hip arthroplasty (THA) decreases postoperative dislocation, however, may leave patients more susceptible to groin pain. Limited data exist for the effect of jumbo femoral heads and acetabular cup position on modern patient-reported outcome measures (PROMs). This study evaluated the effect of jumbo femoral heads and acetabular cup position on PROMs after primary THA.

Characterization of Tumor Antigens from Multi-omics Data: Computational Approaches and Resources.

Tumor-specific antigens, also known as neoantigens, have potential utility in anti-cancer immunotherapy, including immune checkpoint blockade (ICB), neoantigen-specific T cell receptor-engineered T (TCR-T), chimeric antigen receptor T (CAR-T), and therapeutic cancer vaccines (TCVs). After recognizing presented neoantigens, the immune system becomes activated and triggers the death of tumor cells. Neoantigens may be derived from multiple origins, including somatic mutations (single nucleotide variants, insertion/deletions, and gene fusions), circular RNAs, alternative splicing, RNA editing, and polymorphic microbiome.

Model Building with Youth: Applying a System Science Approach to Examine the Dynamic Social Context of Adolescent and Young Adult Marijuana Use.

Marijuana use in adolescence is associated with significant adverse outcomes. Romantic relationships are an important context for marijuana use. Prior research suggests a bi-directional relationship between marijuana use and relationship functioning; however, the complex interplay between adolescent relationship dynamics and marijuana use remains unclear.

Use of Hallway Beds, Radiology Studies, and Patients in Pain on Arrival to the Emergency Department Are Associated With Patient Experience.

Study Objective: Patient experience is an essential measure of patient-centered emergency care. However, emergency department (ED) patient experience scores may be influenced by patient demographics as well as clinical and operational characteristics unrelated to actual patient-centeredness of care. This study aimed to determine whether there are characteristics associated with patient experience scores that have not yet been proposed for risk adjustment by the Centers for Medicare and Medicaid Services (CMS).

MYC and HSF1 Cooperate to Drive Sensitivity to Polo-like Kinase 1 Inhibitor Volasertib in High Grade Serous Ovarian Cancer.

Ovarian cancer is a deadly gynecological disease with frequent recurrence. Current treatments for patients include platinum-based therapy regimens with PARP inhibitors specific for HR-deficient high-grade serous ovarian cancers (HGSOCs). Despite initial effectiveness, patients inevitably develop disease progression as tumor cells acquire resistance.

Some Challenging Questions About Outcomes in Children With Cochlear Implants.

Purpose: Cochlear implants (CIs) have improved the quality of life for many children with severe-to-profound sensorineural hearing loss. Despite the reported CI benefits of improved speech recognition, speech intelligibility, and spoken language processing, large individual differences in speech and language outcomes are still consistently reported in the literature. The enormous variability in CI outcomes has made it challenging to predict which children may be at high risk for limited benefits and how potential risk factors can be improved with interventions.

Deep Learning-Enabled Integration of Histology and Transcriptomics for Tissue Spatial Profile Analysis.

Spatially resolved transcriptomics enable comprehensive measurement of gene expression at subcellular resolution while preserving the spatial context of the tissue microenvironment. While deep learning has shown promise in analyzing SCST datasets, most efforts have focused on sequence data and spatial localization, with limited emphasis on leveraging rich histopathological insights from staining images. We introduce GIST, a deep learning-enabled gene expression and histology integration for spatial cellular profiling.

Factors Associated with Persisting Post-Concussion Symptoms Among Collegiate Athletes and Military Cadets: Findings from the NCAA-DoD CARE Consortium.

Background: Persisting post-concussion symptoms (PPCS) is a condition characterized by prolonged recovery from a mild traumatic brain injury (mTBI) and compromised quality of life. Previous literature, on the basis of small sample sizes, concludes that there are several risk factors for the development of PPCS.

Objective: We seek to identify protective and risk factors for developing slow recovery or persisting post-concussion symptoms (PPCS) by analyzing medical history, contact sport level, setting, and the Sport Concussion Assessment Tool (SCAT) and Brief Symptom Inventory (BSI-18) assessments at baseline and post-injury.

Development and validation of the Food Noise Questionnaire.

Objective: Food noise has received attention in the media, although no validated questionnaires exist to measure it. This study developed and tested the reliability and validity of the Food Noise Questionnaire (FNQ).

Methods: Participants (N = 400) successfully completed, the FNQ and a demographic questionnaire and self-reported weight and height.

Dynamic single cell transcriptomics defines kidney FGF23/KL bioactivity and novel segment-specific inflammatory targets.

Fibroblast growth factor 23 (FGF23) via its coreceptor αKlotho (KL) provides critical control of phosphate metabolism, which is altered in both rare and very common syndromes. However, the spatial-temporal mechanisms dictating kidney FGF23 functions remain poorly understood. Thus, developing approaches to modify specific FGF23-dictated pathways has proven problematic.

Characterization and Targeting of the Main Drivers of Elective Imaging Utilization: A Cross-sectional Study Applying Conjoint Analysis.

Objective: To characterize patient and referring physician preferences when selecting where to have elective imaging performed METHODS: In this Institutional Research Board approved survey-based study, online surveys were completed by 393 patients who had recently had a non-contrast MRI of the shoulder, lumbar spine, or knee within the past 2 years and 168 physicians who had ordered at least 12 such MRIs in the past year. The survey data included explicit questions about preferences as well as a set of conjoint choice screens. Conjoint analysis utilized a logistic model estimated using maximum likelihood estimation.

The ACTION VAD Registry: A Collective Five-Year Experience.

Background: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) began in 2018 as a collaborative learning health system committed to improving outcomes in pediatric heart failure, including children and adults with congenital heart disease, supported with ventricular assist devices (VADs). This report describes patient and device characteristics, and outcomes through 1-year post-implant.

Methods: The ACTION VAD registry report was created from data submitted to the ACTION learning network from April 2018-June 2023.

Impact of Sarcoidosis in Patients Undergoing Aortic Valve Replacement: Insight from Nationwide Readmission Database 2016-2019.

It is not well-known if valve replacement outcomes differ in patients with sarcoidosis, especially in aortic valve intervention where the pressure gradients are physiologically high. In this retrospective study, we included all patients who underwent surgical/transcatheter aortic valve replacement from the National Readmission Database (2016-2019) and then divided them into those with and without sarcoidosis. Logistic and cox proportional hazard regression models were used.

Adapting to evolving MRI data: A transfer learning approach for Alzheimer's disease prediction.

Integrating 3D magnetic resonance imaging (MRI) with machine learning has shown promising results in healthcare, especially in detecting Alzheimer's Disease (AD). However, changes in MRI technologies and acquisition protocols often yield limited data, leading to potential overfitting. This study explores Transfer Learning (TL) approaches to enhance AD diagnosis using a Baseline model consisting of a 3D-Convolutional Neural Network trained on 80 3T MRI scans.

Burden and Risk Factors of Stroke in Vietnam from 1990 to 2021 - A Systematic Analysis from Global Burden Disease 2021.

Background: Stroke is a leading cause of death in Vietnam. However, a comprehensive analysis of stroke burden remains limited. This study aims to investigate the burden of stroke and various risk factors in Vietnam from 1990 to 2021.

Magnetic resonance imaging safety in Asia-Oceania: call for action.

Magnetic Resonance Imaging (MRI) safety is a critical concern in the Asia-Oceania region, as it is elsewhere in the world, due to the unique and complex MRI environment that demands attention. This call-for-action outlines ten critical steps to enhance MRI safety and promote a culture of responsibility and accountability in the Asia-Oceania region. Key focus areas include strengthening education and expertise, improving quality assurance, fostering collaboration, increasing public awareness, and establishing national safety boards.

The interplay of sex and genotype in disease associations: a comprehensive network analysis in the UK Biobank.

Background: Disease comorbidities and longer-term complications, arising from biologically related associations across phenotypes, can lead to increased risk of severe health outcomes. Given that many diseases exhibit sex-specific differences in their genetics, our objective was to determine whether genotype-by-sex (GxS) interactions similarly influence cross-phenotype associations. Through comparison of sex-stratified disease-disease networks (DDNs)-where nodes represent diseases and edges represent their relationships-we investigate sex differences in patterns of polygenicity and pleiotropy between diseases.