C-terminal amides mark proteins for degradation via SCF-FBXO31.

During normal cellular homeostasis, unfolded and mislocalized proteins are recognized and removed, preventing the build-up of toxic byproducts. When protein homeostasis is perturbed during ageing, neurodegeneration or cellular stress, proteins can accumulate several forms of chemical damage through reactive metabolites. Such modifications have been proposed to trigger the selective removal of chemically marked proteins; however, identifying modifications that are sufficient to induce protein degradation has remained challenging.

Efficacy of an Autologous Dermal Fibroblast Injection in Reducing the Retear Rate After Arthroscopic Rotator Cuff Repair: A Prospective Randomized Controlled Trial.

Background: Interest in biological augmentation for improving bone-tendon interface (BTI) healing after arthroscopic rotator cuff repair (ARCR) is growing. Dermal fibroblasts, known for collagen synthesis similar to tenocytes, have shown effectiveness in BTI healing in chronic rotator cuff tear (RCT) models in rabbits. However, no human clinical trials have been conducted.

Impulse Control in Parkinson's Disease: Distinct Effects between Action and Choice.

Aside from typical motor symptoms, impulse control issues related to engaging in actions or decision-making can manifest in Parkinson's disease (PD). The lack of direct comparisons between impulsive action and impulsive choice domains hinders a comprehensive understanding of impaired impulse control in this population. Therefore, the current review integrates findings across behavioural measures of impulsive action and choice in PD samples, both on and off dopaminergic medication.

Large-Scale Validation of the Feasibility of GPT-4 as a Proofreading Tool for Head CT Reports.

Background The increasing workload of radiologists can lead to burnout and errors in radiology reports. Large language models, such as OpenAI's GPT-4, hold promise as error revision tools for radiology. Purpose To test the feasibility of GPT-4 use by determining its error detection, reasoning, and revision performance on head CT reports with varying error types and to validate its clinical utility by comparison with human readers.

Selenium nanoparticles enhance metabolic and nutritional profile in Phaseolus vulgaris: comparative metabolomic and pathway analysis with selenium selenate.

Selenium is a beneficial element in agriculture, particularly for its potential to improve plant growth and stress tolerance at suitable concentrations. In this study, Phaseolus vulgaris was foliar-sprayed with selenium selenate (Se) or selenium nanoparticles (SeNP) at different concentrations during the vegetative stage; afterward, the seed yield was analyzed for metabolomics using H, J-resolved and HSQC NMR data, and NMR databases. A total of 47 metabolites were identified with sugars being the major chemical class.

A genome-wide atlas of human cell morphology.

A key challenge of the modern genomics era is developing empirical data-driven representations of gene function. Here we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-wide genotype-phenotype maps comprising CRISPR-Cas9-based knockouts of >20,000 genes in >30 million cells. Our optical pooled cell profiling platform (PERISCOPE) combines a destainable high-dimensional phenotyping panel (based on Cell Painting) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries.

Guidelines International Network: Principles for Use of Artificial Intelligence in the Health Guideline Enterprise.

Description: Artificial intelligence (AI) has been defined by the High-Level Expert Group on AI of the European Commission as "systems that display intelligent behaviour by analysing their environment and taking actions-with some degree of autonomy-to achieve specific goals." Artificial intelligence has the potential to support guideline planning, development and adaptation, reporting, implementation, impact evaluation, certification, and appraisal of recommendations, which we will refer to as "guideline enterprise." Considering this potential, as well as the lack of guidance for the use of AI in guidelines, the Guidelines International Network (GIN) proposes a set of principles for the development and use of AI tools or processes to support the health guideline enterprise.

Recycling of Post-Consumer Waste Polystyrene Using Commercial Plastic Additives.

Photothermal conversion can promote plastic depolymerization (chemical recycling to a monomer) through light-to-heat conversion. The highly localized temperature gradient near the photothermal agent surface allows selective heating with spatial control not observed with bulk pyrolysis. However, identifying and incorporating practical photothermal agents into plastics for end-of-life depolymerization have not been realized.

Two Cysteines in Raf Kinase Inhibitor Protein Make Differential Contributions to Structural Dynamics In Vitro.

As a scaffolding protein, Raf kinase binding protein (RKIP) is involved in a variety of cellular pathways, including the Raf-MEK-ERK-cascade. It acts as a negative regulator by binding to its partners, making it an attractive target in the development of therapeutic strategies for cancer. Despite its structural stability as a monomer, RKIP may form a dimer, resulting in the switching of binding partners.

Exploring CAR T-Cell Dynamics: Balancing Potent Cytotoxicity and Controlled Inflammation in CAR T-Cells Derived from Systemic Sclerosis and Myositis Patients.

Systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myositis (IIM) are autoimmune diseases managed with long-term immunosuppressive therapies. Hu19-CD828Z, a fully human anti-CD19 chimeric antigen receptor (CAR) with a CD28 costimulatory domain, is engineered to potently deplete B-cells. In this study, we manufactured Hu19-CD828Z CAR T-cells from peripheral blood of SLE, IIM, and SSc patients and healthy donors (HDs).

Comprehensive Metabolomic Profiling in Adults with X-Linked Hypophosphatemia: A Case-Control Study.

Background: X-linked hypophosphatemia (XLH) is a rare disorder characterized by elevated levels of fibroblast growth factor 23 (FGF-23), leading to hypophosphatemia and complications in diagnosis due to its clinical heterogeneity. Metabolomic analysis, which examines metabolites as the final products of cellular processes, is a powerful tool for identifying in vivo biochemical changes, serving as biomarkers of pathological abnormalities, and revealing previously uncharted metabolic pathways.

Methods: A multicenter cross-sectional case-control study of adult patients diagnosed with XLH was conducted.

Methylene blue at recommended concentrations alters metabolism in early zebrafish development.

Methylene blue (MB) is an antifungal agent widely used during critical stages of zebrafish development. Most guidelines recommend 0.00005% or 0.

Comparative Investigation of Vortex and Direct Plasma Discharge for Treating Titanium Surface.

Numerous studies have investigated the surface treatment of implants using various types of plasma, including atmospheric pressure plasma and vacuum plasma, to remove impurities and increase surface energy, thereby enhancing osseointegration. Most previous studies have focused on generating plasma directly on the implant surface by using the implant as an electrode for plasma discharge. However, plasmas generated under atmospheric and moderate vacuum conditions often have a limited plasma volume, meaning the shape of the electrodes significantly influences the local electric field characteristics, which in turn affects plasma behavior.

Free-Breathing Respiratory Triggered High-Pitch Lung CT: Insights From Phantom and Patient Scans.

Objective: Respiratory motion can affect image quality and thus affect the diagnostic accuracy of CT images by masking or mimicking relevant lung pathologies. CT examinations are often performed during deep inspiration and breath-hold to achieve optimal image quality. However, this can be challenging for certain patient groups, such as children, the elderly, or sedated patients.

Lateral Atrial Expression Patterns Provide Insights into Local Transcription Disequilibrium Contributing to Disease Susceptibility.

Background: Transcriptional dysregulation, possibly affected by genetic variation, contributes to disease development. Due to dissimilarities in development, function, and remodeling during disease progression, transcriptional differences between the left atrial (LA) and right atrial (RA) may provide insight into diseases such as atrial fibrillation.

Methods: Lateral differences in atrial transcription were evaluated in CATCH ME (Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly) using a 2-stage discovery and replication design.

A lightweight prosthetic hand with 19-DOF dexterity and human-level functions.

A human hand has 23-degree-of-freedom (DOF) dexterity for managing activities of daily living (ADLs). Current prosthetic hands, primarily driven by motors or pneumatic actuators, fall short in replicating human-level functions, primarily due to limited DOF. Here, we develop a lightweight prosthetic hand that possesses biomimetic 19-DOF dexterity by integrating 38 shape-memory alloy (SMA) actuators to precisely control five fingers and the wrist.

Artificial intelligence-enhanced comprehensive assessment of the aortic valve stenosis continuum in echocardiography.

Background: Transthoracic echocardiography (TTE) is the primary modality for diagnosing aortic stenosis (AS), yet it requires skilled operators and can be resource-intensive. We developed and validated an artificial intelligence (AI)-based system for evaluating AS that is effective in both resource-limited and advanced settings.

Methods: We created a dual-pathway AI system for AS evaluation using a nationwide echocardiographic dataset (developmental dataset, n = 8427): 1) a deep learning (DL)-based AS continuum assessment algorithm using limited 2D TTE videos, and 2) automating conventional AS evaluation.

FFR-Negative Nonculprit High-Risk Plaques and Clinical Outcomes in High-Risk Populations: An Individual Patient-Data Pooled Analysis From COMBINE (OCT-FFR) and PECTUS-obs.

Background: Despite fractional flow reserve (FFR)-guided deferral of revascularization, recurrent events in patients with diabetes or after myocardial infarction remain common. This study aimed to assess the association between FFR-negative but high-risk nonculprit lesions and clinical outcomes.

Methods: This is a patient-level pooled analysis of the prospective natural-history COMBINE (OCT-FFR) study (Optical Coherence Tomography Morphologic and Fractional Flow Reserve Assessment in Diabetes Mellitus Patients) and PECTUS-obs study (Identification of Risk Factors for Acute Coronary Events by OCT After STEMI and NSTEMI Patients With Residual Non- Flow Limiting Lesions).

Diagnostic Accuracy of Hyperdense Artery Sign in Early Detection of Middle Cerebral Artery Infarction: A Cross-Sectional Validation Study.

Background: Hyperdense middle cerebral artery sign (HMCAS) on a non-enhanced multidetector computed tomography (MDCT) scan is considered an important radiological marker in detecting acute arterial thrombotic occlusion, and it is one of the earliest signs of ischemic cerebrovascular accident (CVA). This finding has been observed within 90 min of symptom onset. Modern approaches to patients with cerebral infarction emphasize early diagnosis and management.

Bioinformatics and Computationally Supported Redesign of Aspartase for β-Alanine Synthesis by Acrylic Acid Hydroamination.

Aspartate ammonia lyases catalyze the reversible amination of fumarate to l-aspartate. Recent studies demonstrate that the thermostable enzyme from sp. YM55-1 (AspB) can be engineered for the enantioselective production of substituted β-amino acids.

Disitamab vedotin in preclinical models of HER2-positive breast and gastric cancers resistant to trastuzumab emtansine and trastuzumab deruxtecan.

Background: Most HER2-positive breast or gastric cancers eventually become resistant to the approved anti-HER2 antibody-drug conjugates (ADC) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd). Disitamab vedotin (DV) is a novel anti-HER2 ADC that binds to a different epitope on HER2 compared to trastuzumab. We assessed the efficacy of DV in breast and gastric cancer cell lines and xenografts, including tumor models resistant to T-DM1 and T-DXd.

Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.

Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.

Engineering of CRISPR-Cas PAM recognition using deep learning of vast evolutionary data.

CRISPR-Cas enzymes must recognize a protospacer-adjacent motif (PAM) to edit a genomic site, significantly limiting the range of targetable sequences in a genome. Machine learning-based protein engineering provides a powerful solution to efficiently generate Cas protein variants tailored to recognize specific PAMs. Here, we present Protein2PAM, an evolution-informed deep learning model trained on a dataset of over 45,000 CRISPR-Cas PAMs.

Under pressure in the Eriksen flanker task.

A classical observation in experimental psychology is a reduction in reaction time and response accuracy under time pressure (TP). This speed-accuracy tradeoff may be understood from the combined perspectives of affordance competition and urgency gating. This view implies that action programs compete with each other from stimulus onset until the final response.