Nutritional Interventions to Attenuate Quadriceps Muscle Deficits following Anterior Cruciate Ligament Injury and Reconstruction.

Following anterior cruciate ligament (ACL) injury, quadriceps muscle atrophy persists despite rehabilitation, leading to loss of lower limb strength, osteoarthritis, poor knee joint health and reduced quality of life. However, the molecular mechanisms responsible for these deficits in hypertrophic adaptations within the quadriceps muscle following ACL injury and reconstruction are poorly understood. While resistance exercise training stimulates skeletal muscle hypertrophy, attenuation of these hypertrophic pathways can hinder rehabilitation following ACL injury and reconstruction, and ultimately lead to skeletal muscle atrophy that persists beyond ACL reconstruction, similar to disuse atrophy.

Global Assessment of Emerging Contaminant Removal in Wastewater Treatment Plants: Hazard Screening and Risk Evaluation.

Pharmaceuticals and personal care products (PPCPs) are emerging contaminants (ECs), whose presence in the environment is of increasing concern due to their widespread use and possible detrimental effects on wildlife and humans. These chemicals may present multiple hazardous properties such as environmental persistence, toxicity, high mobility, and the potential for bioaccumulation. In this study, extended bibliographic research was conducted to characterize the removal efficiency (RE) of PPCPs in wastewater treatment plants (WWTPs) considering different technologies.

Prevalence of High-Risk CTA-Based Carotid Plaque-RADS Subtypes in Patients With Embolic Stroke of Undetermined Source.

Background: A modified computed tomography angiography (CTA)-based Carotid Plaque Reporting and Data System (Plaque-RADS) classification was applied to a cohort of patients with embolic stroke of undetermined source to test whether high-risk Plaque-RADS subtypes are more prevalent on the ipsilateral side of stroke. With the widespread use of CTA for stroke evaluation, a CTA-based Plaque-RADS would be valuable for generalizability.

Methods: A retrospective observational cross-sectional study was conducted at a single integrated health system comprised of 3 hospitals with a comprehensive stroke center between October 1, 2015, and April 1, 2017.

Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks.

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.

Arthroscopic Bone Grafting of Deep Acetabular Cysts in Hip Preservation Surgery: A Matched Case-Control Study.

Background: Acetabular subchondral cysts are commonly identified signs of joint degeneration and arthritis. This pathology is generally considered a relative contraindication for hip preservation surgery.

Purpose: To investigate the effect of arthroscopic bone grafting for the treatment of acetabular subchondral cysts.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Improved Image Quality Through Deep Learning Acceleration of Gradient-Echo Acquisitions in Uterine MRI: First Application with the Female Pelvis.

Rationale And Objectives: The aim of this study was to compare the image quality of a deep learning (DL)-accelerated volumetric interpolated breath-hold examination (VIBE) sequence with a standard (ST) VIBE sequence in assessing the uterus.

Materials And Methods: Between April and December 2023, a total of 61 female patients (aged 41 ± 14 years) who were referred for an magnetic resonance imaging (MRI) of the pelvis were included in this prospective study, after providing informed consent. All examinations were performed with a 1.

Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer.

Background: The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.

Methods: In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.

Mineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification.

Background: Vascular calcification is a detrimental aging pathology markedly accelerated in patients with chronic kidney disease. Prelamin A is a biomarker of vascular smooth muscle cell aging that accelerates calcification however the mechanisms remain undefined.

Methods: Vascular smooth muscle cells were transduced with prelamin A using an adenoviral vector and epigenetic modifications were monitored using immunofluorescence and targeted polymerase chain reaction array.

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.

Vaccines in a time of global boiling and megacities.

Neglected tropical diseases are accelerating because of climate change and urbanization to create new clusters of vast urban areas beset by poverty and environmental degradation. These hot and contaminated megacities could enable the rise of parasitic and other tropical infections. A new generation of antiparasitic vaccines will be needed.

Survivorship After Cardiogenic Shock.

Advances in critical care therapies for patients with cardiogenic shock (CS), including temporary mechanical circulatory support and multidisciplinary shock teams, have led to improved survival to hospital discharge, ranging from 60% to 70%. After their index hospitalization, however, survivors of CS may continue to face cardiac as well as extracardiac sequelae of these therapies and complications for years to come. Most studies in CS have focused primarily on survival, with limited data on long-term recovery measures among survivors.

Deep Learning-Enabled Assessment of Right Ventricular Function Improves Prognostication After Transcatheter Edge-to-Edge Repair for Mitral Regurgitation.

Background: Right ventricular (RV) function has a well-established prognostic role in patients with severe mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair (TEER) and is typically assessed using echocardiography-measured tricuspid annular plane systolic excursion. Recently, a deep learning model has been proposed that accurately predicts RV ejection fraction (RVEF) from 2-dimensional echocardiographic videos, with similar diagnostic accuracy as 3-dimensional imaging. This study aimed to evaluate the prognostic value of the deep learning-predicted RVEF values in patients with severe MR undergoing TEER.

Location-specific net water uptake and malignant cerebral edema in acute anterior circulation occlusion ischemic stroke.

Background And Purpose: Early identification of malignant cerebral edema (MCE) in patients with acute ischemic stroke is crucial for timely interventions. We aimed to identify regions critically associated with MCE using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) to evaluate the association between location-specific-net water uptake (NWU) and MCE.

Materials And Methods: This multicentre, retrospective cohort study included patients with acute ischemic stroke following large anterior circulation occlusion.

Symptomatic early coronary graft failure in bypass surgery patients: incidence, predictors and clinical impact.

Objectives: Coronary graft failure (CGF) may occur early after coronary bypass graft surgery (CABG). The study aimed to identify clinical and perioperative risk factors and to evaluate the long-term clinical impact of symptomatic early CGF.

Methods: Patients who underwent clinically indicated coronary angiography (CAG) prior to post-CABG discharge between 2012 and 2022 were included.

Cancer associated fibroblasts drive epithelial to mesenchymal transition and classical to basal change in pancreatic ductal adenocarcinoma cells with loss of IL-8 expression.

Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) carries an extremely poor prognosis, in part resulting from cellular heterogeneity that supports overall tumorigenicity. Cancer associated fibroblasts (CAF) are key determinants of PDAC biology and response to systemic therapy. While CAF subtypes have been defined, the effects of patient-specific CAF heterogeneity and plasticity on tumor cell behavior remain unclear.

Risk of Severe Hypoglycemia After Initiation of Noninsulin Glucose-Lowering Therapies in Adults With Type 2 Diabetes at Moderate Cardiovascular Disease Risk.

In this emulated comparative effectiveness target trial of glucagon-like peptide 1 (GLP-1) receptor agonist, sodium-glucose cotransporter 2 (SGLT2) inhibitor, dipeptidyl peptidase 4 (DPP-4) inhibitor, and sulfonylurea therapy among adults with type 2 diabetes at moderate cardiovascular disease risk, sulfonylurea use was associated with a significantly higher risk of hypoglycemia requiring emergency department or hospital care than treatment with DPP-4 inhibitors, GLP-1 receptor agonists, or SGLT2 inhibitors. This consideration can guide the choice of glucose-lowering therapy in this highly prevalent patient population, in whom avoidance of hypoglycemia is important, yet among whom the risk of severe hypoglycemia has not been examined previously.

Clinical entity augmented retrieval for clinical information extraction.

Large language models (LLMs) with retrieval-augmented generation (RAG) have improved information extraction over previous methods, yet their reliance on embeddings often leads to inefficient retrieval. We introduce CLinical Entity Augmented Retrieval (CLEAR), a RAG pipeline that retrieves information using entities. We compared CLEAR to embedding RAG and full-note approaches for extracting 18 variables using six LLMs across 20,000 clinical notes.

FORCE platform overcomes barriers of oligonucleotide delivery to muscle and corrects myotonic dystrophy features in preclinical models.

Background: We developed the FORCE platform to overcome limitations of oligonucleotide delivery to muscle and enable their applicability to neuromuscular disorders. The platform consists of an antigen-binding fragment, highly specific for the human transferrin receptor 1 (TfR1), conjugated to an oligonucleotide via a cleavable valine-citrulline linker. Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by expanded CUG triplets in the DMPK RNA, which sequester splicing proteins in the nucleus, lead to spliceopathy, and drive disease progression.

Motion-Compensated Multishot Pancreatic Diffusion-Weighted Imaging With Deep Learning-Based Denoising.

Objectives: Pancreatic diffusion-weighted imaging (DWI) has numerous clinical applications, but conventional single-shot methods suffer from off resonance-induced artifacts like distortion and blurring while cardiovascular motion-induced phase inconsistency leads to quantitative errors and signal loss, limiting its utility. Multishot DWI (msDWI) offers reduced image distortion and blurring relative to single-shot methods but increases sensitivity to motion artifacts. Motion-compensated diffusion-encoding gradients (MCGs) reduce motion artifacts and could improve motion robustness of msDWI but come with the cost of extended echo time, further reducing signal.

CT Angiography, MR Angiography, and Their Combined Use for Detection of Unruptured Intracranial Aneurysms: Comparison with Digital Subtraction Angiography and 3-dimensional Rotational Angiography.

Purpose: To compare the diagnostic accuracy of CT angiography (CTA), MR angiography (MRA), and their combined use for detecting unruptured intracranial aneurysms (UIAs).

Methods: Between September 2019 and August 2023, 235 patients suspected of having UIA underwent CTA, MRA, and digital subtraction angiography (DSA)/3-dimensional rotational angiography (3DRA). Two neuroradiologists retrospectively reviewed these images for UIA presence.

Uptake and safety of Sotrovimab for prevention of severe COVID-19 in a cohort and self-controlled case series study.

Background: Sotrovimab is a neutralising monoclonal antibody (nMAB) currently available to treat extremely clinically vulnerable COVID-19 patients in England. Trials have shown it to have mild to moderate side effects, however, evidence regarding its safety in real-world settings remains insufficient.

Methods: Descriptive and multivariable logistic regression analyses were conducted to evaluate uptake, and a self-controlled case series analysis performed to measure the risk of hospital admission (hospitalisation) associated with 49 pre-specified suspected adverse outcomes in the period 2-28 days post-Sotrovimab treatment among eligible patients treated between December 11, 2021 and May 24, 2022.