EndoVIA for quantifying A-to-I editing and mapping the subcellular localization of edited transcripts.

Adenosine-to-inosine (A-to-I) editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a prevalent post-transcriptional modification that is vital for numerous biological functions. Given that this modification impacts global gene expression, RNA localization, and innate cellular immunity, dysregulation of A-to-I editing has unsurprisingly been linked to a variety of cancers and other diseases. However, our current understanding of the underpinning mechanisms that connect dysregulated A-to-I editing and disease processes remains limited.

Retinoids and retinoid-binding proteins: Unexpected roles in metabolic disease.

Alterations in tissue expression levels of both retinol-binding protein 2 (RBP2) and retinol-binding protein 4 (RBP4) have been associated with metabolic disease, specifically with obesity, glucose intolerance and hepatic steatosis. Our laboratories have shown that this involves novel pathways not previously considered as possible linkages between impaired retinoid metabolism and metabolic disease development. We have established both biochemically and structurally that RBP2 binds with very high affinity to very long-chain unsaturated 2-monoacylglycerols like the canonical endocannabinoid 2-arachidonoyl glycerol (2-AG) and other endocannabinoid-like substances.

The interplay between retinoic acid binding proteins and retinoic acid degrading enzymes in modulating retinoic acid concentrations.

The active metabolite of vitamin A, all-trans-retinoic acid (atRA), is critical for maintenance of many cellular processes. Although the enzymes that can synthesize and clear atRA in mammals have been identified, their tissue and cell-type specific roles are still not fully established. Based on the plasma protein binding, tissue distribution and lipophilicity of atRA, atRA partitions extensively to lipid membranes and other neutral lipids in cells.

The action of retinoic acid on spermatogonia in the testis.

For mammalian spermatogenesis to proceed normally, it is essential that the population of testicular progenitor cells, A undifferentiated spermatogonia (A), undergoes differentiation during the A to A1 transition that occurs at the onset of spermatogenesis. The commitment of the A population to differentiation and leaving a quiescent, stem-like state gives rise to all the spermatozoa produced across the lifespan of an individual, and ultimately determines male fertility. The action of all-trans retinoic acid (atRA) on the A population is the determining factor that induces this change.

Intensive care unit acquired weakness and physical rehabilitation in the ICU.

Approximately half of critically ill adults experience intensive care unit acquired weakness (ICUAW). Patients who develop ICUAW may have negative outcomes, including longer duration of mechanical ventilation, greater length of stay, and worse mobility, physical functioning, quality of life, and mortality. Early physical rehabilitation interventions have potential for improving ICUAW; however, randomized trials show inconsistent findings on the efficacy of these interventions.

The Autonomic Nervous System and Inflammation in Chronic Kidney Disease.

The autonomic nervous system plays a crucial role in regulating physiological processes and maintaining homeostasis through its two branches: the sympathetic nervous system (SNS) and the parasympathetic nervous system. Dysregulation of the autonomic system, characterized by increased sympathetic activity and reduced parasympathetic tone, is a common feature in chronic kidney disease (CKD) and cardiovascular disease. This imbalance contributes to a pro-inflammatory state, exacerbating disease progression and increasing the risk for cardiovascular events.

Supporting Unhealthy Substance use care Through a whole person Approach and user centered INtegration into primary care (SUSTAIN): Study protocol for a type 2 hybrid effectiveness-implementation trial.

Background: Unhealthy substance use (USU) is common and ranges from use above guideline-recommended levels to severe substance use disorder. USU results in substantial morbidity and mortality yet primary care practices rarely systematically screen, diagnose, and treat USU. Supporting Unhealthy Substance use care Through a whole person Approach and user centered INtegration into primary care (SUSTAIN) tests whether the implementation of a co-designed change package for USU improves patient function.

Clinical outcomes in peripheral ulcerative keratitis.

Purpose: To evaluate clinical and treatment outcomes in patients with peripheral ulcerative keratitis (PUK).

Design: Retrospective, case series SUBJECTS: Patients diagnosed with PUK at the Wilmer Eye Institute between January 2003 and October 2022.

Methods: Data collected included demographics, presence of systemic disease, disease laterality, duration of disease, PUK activity, presence of corneal perforation, and treatments.

SEMI-AUTOMATED EXTRACTION OF RESEARCH TOPICS AND TRENDS FROM NCI FUNDING IN RADIOLOGICAL SCIENCES FROM 2000-2020.

Background: Investigators and funding organizations desire knowledge on topics and trends in publicly funded research but current efforts for manual categorization have been limited in breadth and depth of understanding.

Purpose: We present a semi-automated analysis of 21 years of R-type National Cancer Institute (NCI) grants to departments of radiation oncology and radiology using natural language processing (NLP).

Methods: We selected all non-education R-type NCI grants from 2000 to 2020 awarded to departments of radiation oncology/radiology with affiliated schools of medicine.

Narrow elliptical motion at the outer hair cell-Deiters' cell junction explains disparate features of uniaxial displacement measurements.

Sound-evoked displacement responses at the outer hair cell-Deiters' cell junction (OHC-DC) are of significant interest in cochlear mechanics, as OHCs are believed to be in part responsible for active tuning enhancement and amplification. Motion in the cochlea is three-dimensional, and the architecture of the organ of Corti complex (OCC) suggests the presence and mechanical importance of all three components of motion. Optical coherence tomography (OCT) displacement measurements of OHC-DC motion from different experimental preparations often show disparate results, potentially due to OCT measuring only the motion component along the beam axis.

Psychosocial interventions for children and adolescents with adverse childhood experiences: A systematic review and meta-analysis.

Backgrounds: Exposure to adverse childhood experiences (ACEs) is associated with adverse neurobiological, developmental, cognitive, behavioral, psychological, and social consequences among children and adolescents. Psychosocial interventions hold promise for mitigating the negative impacts of ACEs, but there is a lack of updated and comprehensive evidence summarizing their effects qualitatively and quantitatively.

Aims: We performed a systematic review and meta-analysis of existing evidence on the effectiveness of psychosocial interventions on children's outcomes, including internalizing and externalizing problems.

Bioconjugation of Synthetic Peptides onto Universal Chimeric Antigen Receptor T Cells for Targeted Cancer Immunotherapies.

The recent development of modular universal chimeric antigen receptor (CAR) T-cell platforms that use bifunctional adaptor intermediates to redirect engineered T-cell effector function has greatly expanded the capabilities of adoptive T-cell therapy, enabling safer and more comprehensive cancer treatment. However, universal CAR receptor systems rely on unstable transient recognition of tag-coupled intermediates for T-cell activation, and the array of targeting intermediates has been limited to antibodies and small molecules. Addressing these shortcomings, we engineered universal CAR T-cell receptors that can be covalently modified with synthetic biomaterials by accelerated SpyCatcher003-SpyTag003 chemistry for cancer-cell targeting.

Health Expenditures of Patients With Diabetes After Bariatric Surgery: Comparing Gastric Bypass and Sleeve Gastrectomy.

Background: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) differ in their effects on body weight and risk for reoperation. However, it is unclear whether long-term health expenditures differ by procedure type in patients with diabetes.

Objective: To compare health expenditures 3 years before and 5.

Accuracy and Safety of AI-Enabled Scribe Technology: Instrument Validation Study.

Artificial intelligence-enabled ambient digital scribes may have many potential benefits, yet results from our study indicate that there are errors that must be evaluated to mitigate safety risks.

Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors.

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma.

An Artificial Intelligence Model Using Diffusion Basis Spectrum Imaging Metrics Accurately Predicts Clinically Significant Prostate Cancer.

Purpose: Conventional prostate magnetic resonance imaging has limited accuracy for clinically significant prostate cancer (csPCa). We performed diffusion basis spectrum imaging (DBSI) prior to biopsy and applied artificial intelligence models to these DBSI metrics to predict csPCa.

Materials And Methods: Between February 2020 and March 2024, 241 patients underwent prostate MRI that included conventional and DBSI-specific sequences prior to prostate biopsy.

Automating the practice of science: Opportunities, challenges, and implications.

Automation transformed various aspects of our human civilization, revolutionizing industries and streamlining processes. In the domain of scientific inquiry, automated approaches emerged as powerful tools, holding promise for accelerating discovery, enhancing reproducibility, and overcoming the traditional impediments to scientific progress. This article evaluates the scope of automation within scientific practice and assesses recent approaches.

Discourse on measurement.

Measurement literacy is required for strong scientific reasoning, effective experimental design, conceptual and empirical validation of measurement quantities, and the intelligible interpretation of error in theory construction. This discourse examines how issues in measurement are posed and resolved and addresses potential misunderstandings. Examples drawn from across the sciences are used to show that measurement literacy promotes the goals of scientific discourse and provides the necessary foundation for carving out perspectives and carrying out interventions in science.

How should the advancement of large language models affect the practice of science?

Large language models (LLMs) are being increasingly incorporated into scientific workflows. However, we have yet to fully grasp the implications of this integration. How should the advancement of large language models affect the practice of science? For this opinion piece, we have invited four diverse groups of scientists to reflect on this query, sharing their perspectives and engaging in debate.

Intraspecific Variation and Recent Loss of Ancient, Conserved Effector Genes in the Sudden Oak Death Pathogen .

Members of the genus are responsible for many important diseases in agricultural and natural ecosystems. causes devastating diseases of oak, and tanoak stands in US forests and larch in the UK. The four evolutionary lineages involved express different virulence phenotypes on plant hosts, and characterization of gene content is foundational to understanding the basis for these differences.

Transient Ischemic Attack in Women: Real-World Hospitalization Incidence, Outcomes, and Risk of Hemorrhage and Stroke.

Background: Sex-specific differences in stroke risk factors, clinical presentation, and outcomes are well documented. However, little is known about real-world differences in transient ischemic attack (TIA) hospitalizations and outcomes between men and women.

Methods: This was a retrospective cohort study of the 2016 to 2021 Nationwide Readmissions Database in the United States.

Preliminary investigation of an artificial intelligence-based cognitive behavioral therapy training tool.

We developed an asynchronous online cognitive behavioral therapy (CBT) training tool that provides artificial intelligence- (AI-) enabled feedback to learners across eight CBT skills. We sought to evaluate the technical reliability and to ascertain how practitioners would use the tool to inform product iteration and future deployment. We conducted a single-arm 2-week field trial among behavioral health practitioners who treat outpatients with psychosis.