NEDD4-Mediated GSNOR Degradation Aggravates Cardiac Hypertrophy and Dysfunction.

Background: The decrease in S-nitrosoglutathione reductase (GSNOR) leads to an elevation of S-nitrosylation, thereby exacerbating the progression of cardiomyopathy in response to hemodynamic stress. However, the mechanisms under GSNOR decrease remain unclear. Here, we identify NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) as a novel molecule that plays a crucial role in the pathogenesis of pressure overload-induced cardiac hypertrophy, by modulating GSNOR levels, thereby demonstrating significant therapeutic potential.

Chemical shift encoding based double bonds quantification in triglycerides using deep image prior.

Fatty acid can potentially serve as biomarker for evaluating metabolic disorder and inflammation condition, and quantifying the double bonds is the key for revealing fatty acid information. This study presents an assessment of a deep learning approach utilizing deep image prior (DIP) for the quantification of double bonds and methylene-interrupted double bonds of triglyceride derived from chemical-shift encoded multi-echo gradient echo images, all achieved without the necessity for network training. The methodology implemented a cost function grounded in signal constraints to continually refine the neural network's parameters on a single slice of images through iterative processes.

Integration of Deep Learning and Sub-regional Radiomics Improves the Prediction of Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients.

Rationale And Objectives: The precise prediction of response to neoadjuvant chemoradiotherapy is crucial for tailoring perioperative treatment in patients diagnosed with locally advanced rectal cancer (LARC). This retrospective study aims to develop and validate a model that integrates deep learning and sub-regional radiomics from MRI imaging to predict pathological complete response (pCR) in patients with LARC.

Materials And Methods: We retrospectively enrolled 768 eligible participants from three independent hospitals who had received neoadjuvant chemoradiotherapy followed by radical surgery.

Evaluating Neoadjuvant Immunochemotherapeutic Response for Bladder Carcinoma Using Amide Proton Transfer-Weighted MRI.

Rationale And Objectives: To investigate the feasibility of amide proton transfer-weighted (APTw) and diffusion-weighted MRI in evaluating the response of bladder cancer (BCa) to neoadjuvant immunochemotherapy.

Materials And Methods: From June 2021 to July 2023, participants with pathologically confirmed BCa were prospectively recruited to undergo MRI examinations, including APTw and diffusion-weighted MRI before and after neoadjuvant immunochemotherapy. Histogram analysis features (mean, median, and entropy) were extracted from pre- and post-treatment APTw and apparent diffusion coefficient (ADC) maps, respectively.

Toward expert-level medical question answering with large language models.

Large language models (LLMs) have shown promise in medical question answering, with Med-PaLM being the first to exceed a 'passing' score in United States Medical Licensing Examination style questions. However, challenges remain in long-form medical question answering and handling real-world workflows. Here, we present Med-PaLM 2, which bridges these gaps with a combination of base LLM improvements, medical domain fine-tuning and new strategies for improving reasoning and grounding through ensemble refinement and chain of retrieval.

Maximizing Nano-Silica Efficiency in Laboratory-Simulated Recycled Concrete Aggregate via Prior Accelerated Carbonation: An Effective Strategy to Up-Cycle Construction Wastes.

Herein, the study explores a composite modification approach to enhance the use of recycled concrete aggregate (RCA) in sustainable construction by combining accelerated carbonation (AC) and nano-silica immersion (NS). RCA, a major source of construction waste, faces challenges in achieving comparable properties to virgin aggregates. Nano-silica, a potent pozzolan, is added to fill micro-cracks and voids in RCA, improving its bonding and strength.

Elucidation of a distinct photoreduction pathway in class II photolyase.

Class II photolyases (PLs) are a distant subclade in the photolyase/cryptochrome superfamily, displaying a unique Trp-Tyr tetrad for photoreduction and exhibiting a lower quantum yield (QY) of DNA repair (49%) than class I photolyases (82%) [M. Zhang, L. Wang, S.

Multimodal Deep Learning Fusing Clinical and Radiomics Scores for Prediction of Early-Stage Lung Adenocarcinoma Lymph Node Metastasis.

Rationale And Objectives: To develop and validate a multimodal deep learning (DL) model based on computed tomography (CT) images and clinical knowledge to predict lymph node metastasis (LNM) in early lung adenocarcinoma.

Materials And Methods: A total of 724 pathologically confirmed early invasive lung adenocarcinoma patients were retrospectively included from two centers. Clinical and CT semantic features of the patients were collected, and 3D radiomics features were extracted from nonenhanced CT images.

Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer.

The efficacy of immunotherapy for estrogen receptor-positive/HER2-negative (ER+/HER2-) metastatic breast cancer (MBC) has not been proven. We conduct a phase 1b/2 trial to assess the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with premenopausal ER+/HER2- MBC who had failed one to two lines of hormone therapy (HT) without chemotherapy. The primary endpoint of progression-free survival rate at 8 months (i.

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach.

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health.

A Systematic Method to Detect Next-Generation Sequencing-Based Microsatellite Instability in Plasma Cell-Free DNA: plasmaMSI.

Microsatellite instability (MSI) detection using tumor tissue is a well-established prognostic and predictive biomarker for certain types of cancers. However, tumor tissue samples are less convenient to obtain than blood plasma samples. The main challenge facing next-generation sequencing-based MSI detection in blood plasma samples is the ultralow signal/noise ratio in plasma cell-free DNA (cfDNA).

Dual Antiplatelet Treatment up to 72 Hours After Ischemic Stroke Stratified by Risk Profile: A Post Hoc Analysis.

Background: Risk profile of recurrence may influence the effect of antiplatelet therapy. This study aimed to evaluate the efficacy and safety of clopidogrel-aspirin initiated within 72 hours after symptom onset for acute mild stroke or high-risk transient ischemic attack stratified by risk profile.

Methods: This is a secondary post hoc analysis of the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis) randomized clinical trial that enrolled patients 35 to 80 years old with acute mild ischemic stroke or high-risk transient ischemic attack between 2018 and 2022.

Diagnosis of liver hemangioma using magnetic resonance diffusion-derived vessel density (DDVD) pixelwise map: a preliminary descriptive study.

Background: Liver hemangiomas (HGs) are characterized by cavernous venous spaces delineated by a lining of vascular endothelial cells and interspersed with connective tissue septa. Typically, a liver HG has higher apparent diffusion coefficient (ADC) and T2 values than those of hepatocellular carcinomas (HCCs) and liver metastases, and lower ADC and T2 values than those of liver simple cysts. However, a portion of HGs shows ADC and T2 overlapping with those of HCC, liver metastasis, and simple cyst.

A robust benchmark for detecting low-frequency variants in the HG002 Genome In A Bottle NIST reference material.

Somatic mosaicism is an important cause of disease, but mosaic and somatic variants are often challenging to detect because they exist in only a fraction of cells. To address the need for benchmarking subclonal variants in normal cell populations, we developed a benchmark containing mosaic variants in the Genome in a Bottle Consortium (GIAB) HG002 reference material DNA from a large batch of a normal lymphoblastoid cell line. First, we used a somatic variant caller with high coverage (300x) Illumina whole genome sequencing data from the Ashkenazi Jewish trio to detect variants in HG002 not detected in at least 5% of cells from the combined parental data.

Clinical Classification and Management Outcomes of Anterior Segment-Dominated Persistent Fetal Vasculature: The CCPMOH Report.

Purpose: To describe clinical features, management, and outcomes of anterior segment-dominated persistent fetal vasculature (aPFV).

Design: A secondary analysis of aPFV data from a longitudinal cohort study.

Methods: The age and gender of each participant upon initial presentation, along with biological parameters, best-corrected visual acuity, and biomicroscopic assessments were collected.

Virtual MR Elastography and Multi-b-value DWI Models for Predicting Microvascular Invasion in Solitary BCLC Stage A Hepatocellular Carcinoma.

Rationale And Objectives: To evaluate the performance of virtual MR elastography (vMRE) for predicting microvascular invasion (MVI) in Barcelona Clinic Liver Cancer (BCLC) stage A (≤ 5.0 cm) hepatocellular carcinoma (HCC) and to construct a combined nomogram based on vMRE, multi-b-value DWI models, and clinical-radiological (CR) features.

Methods: Consecutive patients with suspected HCC who underwent multi-b-value DWI examinations were prospectively collected.

Patient-Reported Outcomes after Surgery for Pigmented Villonodular Synovitis in the Knee: A Cohort Study.

Pigmented villonodular synovitis (PVNS) is a rare neoplastic proliferation of large joints, including the knee, with both localized PVNS (LPVNS) and diffuse PVNS (DPVNS) types. DPVNS is known to recur at a higher rate following resection; however, there is little evidence comparing patient-reported outcomes (PROs) between the two types. The purpose of this study was to compare PROs between patients with LPVNS and DPVNS involving the knee 2 years after surgical resection.

The lives of cells, recorded.

A paradigm for biology is emerging in which cells can be genetically programmed to write their histories into their own genomes. These records can subsequently be read, and the cellular histories reconstructed, which for each cell could include a record of its lineage relationships, extrinsic influences, internal states and physical locations, over time. DNA recording has the potential to transform the way that we study developmental and disease processes.

Phenotype driven molecular genetic test recommendation for diagnosing pediatric rare disorders.

Patients with rare diseases often experience prolonged diagnostic delays. Ordering appropriate genetic tests is crucial yet challenging, especially for general pediatricians without genetic expertise. Recent American College of Medical Genetics (ACMG) guidelines embrace early use of exome sequencing (ES) or genome sequencing (GS) for conditions like congenital anomalies or developmental delays while still recommend gene panels for patients exhibiting strong manifestations of a specific disease.

Adjunctive Middle Meningeal Artery Embolization for Subdural Hematoma.

Background: Subacute and chronic subdural hematomas are common and frequently recur after surgical evacuation. The effect of adjunctive middle meningeal artery embolization on the risk of reoperation remains unclear.

Methods: In a prospective, multicenter, interventional, adaptive-design trial, we randomly assigned patients with symptomatic subacute or chronic subdural hematoma with an indication for surgical evacuation to undergo middle meningeal artery embolization plus surgery (treatment group) or surgery alone (control group).

Health Economic Evaluation of Antimicrobial Stewardship, Procalcitonin Testing, and Rapid Blood Culture Identification in Sepsis Care: A 90-Day Model-Based, Cost-Utility Analysis.

Objective: We evaluated the cost-effectiveness of a bundled intervention including an antimicrobial stewardship program (ASP), procalcitonin (PCT) testing, and rapid blood culture identification (BCID), compared with pre-implementation standard care in critically ill adult patients with sepsis.

Methods: We conducted a decision tree model-based cost-effectiveness analysis alongside a previously published pre- and post-implementation quality improvement study. We adopted a public Canadian healthcare payer's perspective.

Plasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau Pathology at F-SynVesT-1 Brain PET Imaging.

Background Synaptic loss is an important factor in Alzheimer disease (AD); however, blood assays that conveniently and rapidly reflect changes in synaptic density are lacking. Purpose To correlate multiple potential synaptic blood markers with synaptic density measured using F-SynVesT-1, a fluorine 18 (F)-labeled radiotracer, brain PET and to explore the independent associations between these markers and synaptic density. Materials and Methods This prospective study included 50 cognitively unimpaired (mean age, 65.

A pan-orthoebolavirus neutralizing antibody encoded by mRNA effectively prevents virus infection.

is a genus of hazardous pathogens that has caused over 30 outbreaks. However, currently approved therapies are limited in scope, as they are only effective against the Ebola virus and lack cross-protection against other orthoebolaviruses. Here, we demonstrate that a previously isolated human-derived antibody, 2G1, can recognize the glycoprotein (GP) of every orthoebolavirus species.