Cardiac compressed sensing real-time cine for the assessment of left ventricular function: a large sample size analysis.

Background: Segmented cine imaging using a balanced steady-state free precession sequence is the gold standard for accurately quantifying cardiac function and myocardial mass. However, this method suffers from inefficient K-space sampling, resulting in long scan times, and requires multiple breath holds that can be difficult for some patients. Real-time compressed sensing (CS) cine reduces image acquisition time through K-space undersampling and iterative reconstruction, enabling rapid magnetic resonance (MR) imaging.

Disentangling Neurodegeneration From Aging in Multiple Sclerosis Using Deep Learning: The Brain-Predicted Disease Duration Gap.

Background And Objectives: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS.

A comprehensive study of SARS-CoV-2 main protease (Mpro) inhibitor-resistant mutants selected in a VSV-based system.

Nirmatrelvir was the first protease inhibitor specifically developed against the SARS-CoV-2 main protease (3CLpro/Mpro) and licensed for clinical use. As SARS-CoV-2 continues to spread, variants resistant to nirmatrelvir and other currently available treatments are likely to arise. This study aimed to identify and characterize mutations that confer resistance to nirmatrelvir.

Analyzing Formation and Absorption of Avascular Subretinal Hyperreflective Material in nAMD From OCTA-Based Insights.

Purpose: To investigate the formation and absorption of avascular subretinal hyperreflective material (avSHRM) in neovascular age-related macular degeneration (nAMD) based on optical coherence tomography angiography (OCTA) characteristics.

Design: Prospective cohort study.

Methods: This study included patients with treatment-naive nAMD who were followed up for 3 months.

PD-1 blockade enhances the effect of targeted chemotherapy on locally advanced pMMR/MSS colorectal cancer.

Background: Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies).

Implications of Race Adjustment in Lung-Function Equations.

Background: Adjustment for race is discouraged in lung-function testing, but the implications of adopting race-neutral equations have not been comprehensively quantified.

Methods: We obtained longitudinal data from 369,077 participants in the National Health and Nutrition Examination Survey, U.K.

Network-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis.

Aberrant signaling pathway activity is a hallmark of tumorigenesis and progression, which has guided targeted inhibitor design for over 30 years. Yet, adaptive resistance mechanisms, induced by rapid, context-specific signaling network rewiring, continue to challenge therapeutic efficacy. Leveraging progress in proteomic technologies and network-based methodologies, we introduce Virtual Enrichment-based Signaling Protein-activity Analysis (VESPA)-an algorithm designed to elucidate mechanisms of cell response and adaptation to drug perturbations-and use it to analyze 7-point phosphoproteomic time series from colorectal cancer cells treated with clinically-relevant inhibitors and control media.

Multicenter Evaluation of a Weakly Supervised Deep Learning Model for Lymph Node Diagnosis in Rectal Cancer at MRI.

Purpose To develop a Weakly supervISed model DevelOpment fraMework (WISDOM) model to construct a lymph node (LN) diagnosis model for patients with rectal cancer (RC) that uses preoperative MRI data coupled with postoperative patient-level pathologic information. Materials and Methods In this retrospective study, the WISDOM model was built using MRI (T2-weighted and diffusion-weighted imaging) and patient-level pathologic information (the number of postoperatively confirmed metastatic LNs and resected LNs) based on the data of patients with RC between January 2016 and November 2017. The incremental value of the model in assisting radiologists was investigated.

Transcriptome Profiling Identifies Differentially Expressed Genes in Skeletal Muscle Development in Native Chinese Ducks.

China boasts a rich diversity of indigenous duck species, some of which exhibit desirable economic traits. Here, we generated transcriptome sequencing datasets of breast muscle tissue samples from 1D of four groups: Pekin duck pure breeding group (P), Jinling White duck breeding group (J), P ♂ × J ♀ orthogonal group (PJ) and J ♂ × P ♀ reciprocal-cross group (JP) ( = 3), chosen based on the distinctive characteristics of duck muscle development during the embryonic period. We identified 5053 differentially expressed genes (DEGs) among the four groups.

Extracellular Matrix Disorganization Caused by ADAMTS16 Deficiency Leads to Bicuspid Aortic Valve With Raphe Formation.

Background: A better understanding of the molecular mechanism of aortic valve development and bicuspid aortic valve (BAV) formation would significantly improve and optimize the therapeutic strategy for BAV treatment. Over the past decade, the genes involved in aortic valve development and BAV formation have been increasingly recognized. On the other hand, (a disintegrin and metalloproteinase with thrombospondin motifs) gene family members have been reported to be able to modulate cardiovascular development and diseases.

Flipped C-Terminal Ends of APOA1 Promote ABCA1-Dependent Cholesterol Efflux by Small HDLs.

Background: Cholesterol efflux capacity (CEC) predicts cardiovascular disease independently of high-density lipoprotein (HDL) cholesterol levels. Isolated small HDL particles are potent promoters of macrophage CEC by the ABCA1 (ATP-binding cassette transporter A1) pathway, but the underlying mechanisms are unclear.

Methods: We used model system studies of reconstituted HDL and plasma from control and lecithin-cholesterol acyltransferase (LCAT)-deficient subjects to investigate the relationships among the sizes of HDL particles, the structure of APOA1 (apolipoprotein A1) in the different particles, and the CECs of plasma and isolated HDLs.

Determination of Spin-Parity Quantum Numbers for the Narrow Structure near the pΛ[over ¯] Threshold in e^{+}e^{-}→pK^{-}Λ[over ¯]+c.c.

A narrow structure in the pΛ[over ¯] system near the mass threshold, named as X(2085), is observed in the process e^{+}e^{-}→pK^{-}Λ[over ¯] with a statistical significance greater than 20σ. Its spin and parity are determined for the first time to be J^{P}=1^{+} in an amplitude analysis, with a statistical significance greater than 5σ over other quantum numbers (0^{-},1^{-} and 2^{+}). The pole positions of X(2085) are measured to be M_{pole}=(2084_{-2}^{+4}±9)  MeV and Γ_{pole}=(58_{-3}^{+4}±25)  MeV, where the first uncertainties are statistical and the second ones are systematic.

Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma.

Background: No new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy.

Methods: In this phase 3, multinational, open-label trial, we randomly assigned patients with previously untreated unresectable or metastatic urothelial carcinoma either to receive intravenous nivolumab (at a dose of 360 mg) plus gemcitabine-cisplatin (nivolumab combination) every 3 weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine-cisplatin alone every 3 weeks for up to six cycles. The primary outcomes were overall and progression-free survival.

A Combined Model Integrating Radiomics and Deep Learning Based on Contrast-Enhanced CT for Preoperative Staging of Laryngeal Carcinoma.

Rationale And Objectives: Accurate staging of laryngeal carcinoma can inform appropriate treatment decision-making. We developed a radiomics model, a deep learning (DL) model, and a combined model (incorporating radiomics features and DL features) based on the venous-phase CT images and explored the performance of these models in stratifying patients with laryngeal carcinoma into stage I-II and stage III-IV, and also compared these models with radiologists.

Materials And Methods: Three hundreds and nineteen patients with pathologically confirmed laryngeal carcinoma were randomly divided into a training set (n = 223) and a test set (n = 96).

Rationally designed chimeric PI3K-BET bromodomain inhibitors elicit curative responses in MYC-driven lymphoma.

Targeted inhibitors of bromodomain and extraterminal (BET)-bromodomains and phosphatidylinositol-3-kinase (PI3K) signaling demonstrate potent but self-limited antilymphoma activity as single agents in the context of cellular Myelocytomatosis () oncogene-dysregulation. However, combined PI3K and BET inhibition imparts synergistic anticancer activity with the potential for more sustained disease responses due to the mutual antagonism of compensatory epigenetic and signaling networks. Here, we describe the mechanistic and therapeutic validation of rationally designed dual PI3K/BET bromodomain inhibitors, built by linkage of established PI3K and BET inhibitor pharmacophores.

Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively.

Risk for Chronic Kidney Disease Progression After Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort Study.

Background: Prior studies associating acute kidney injury (AKI) with more rapid subsequent loss of kidney function had methodological limitations, including inadequate control for differences between patients who had AKI and those who did not.

Objective: To determine whether AKI is independently associated with subsequent kidney function trajectory among patients with chronic kidney disease (CKD).

Design: Multicenter prospective cohort study.

Lung Volume Dependence and Repeatability of Hyperpolarized Xe MRI Gas Uptake Metrics in Healthy Volunteers and Participants with COPD.

Purpose: To assess the effect of lung volume on measured values and repeatability of xenon 129 (Xe) gas uptake metrics in healthy volunteers and participants with chronic obstructive pulmonary disease (COPD).

Materials And Methods: This Health Insurance Portability and Accountability Act-compliant prospective study included data (March 2014-December 2015) from 49 participants (19 with COPD [mean age, 67 years ± 9 (SD)]; nine women]; 25 older healthy volunteers [mean age, 59 years ± 10; 20 women]; and five young healthy women [mean age, 23 years ± 3]). Thirty-two participants underwent repeated Xe and same-breath-hold proton MRI at residual volume plus one-third forced vital capacity (RV+FVC/3), with 29 also undergoing one examination at total lung capacity (TLC).

MEDIPIPE: an automated and comprehensive pipeline for cfMeDIP-seq data quality control and analysis.

Summary: Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) has emerged as a promising liquid biopsy technology to detect cancers and monitor treatments. While several bioinformatics tools for DNA methylation analysis have been adapted for cfMeDIP-seq data, an end-to-end pipeline and quality control framework specifically for this data type is still lacking. Here, we present the MEDIPIPE, which provides a one-stop solution for cfMeDIP-seq data quality control, methylation quantification, and sample aggregation.

Probing the Association between Acute Kidney Injury and Cardiovascular Outcomes.

Background: Patients hospitalized with AKI have higher subsequent risks of heart failure, atherosclerotic cardiovascular events, and mortality than their counterparts without AKI, but these higher risks may be due to differences in prehospitalization patient characteristics, including the baseline level of estimated glomerular filtration rate (eGFR), the rate of prior eGFR decline, and the proteinuria level, rather than AKI itself.

Methods: Among 2177 adult participants in the Chronic Renal Insufficiency Cohort study who were hospitalized in 2013-2019, we compared subsequent risks of heart failure, atherosclerotic cardiovascular events, and mortality between those with serum creatinine-based AKI (495 patients) and those without AKI (1682 patients). We report both crude associations and associations sequentially adjusted for prehospitalization characteristics including eGFR, eGFR slope, and urine protein-creatinine ratio (UPCR).

Large scale crowdsourced radiotherapy segmentations across a variety of cancer anatomic sites.

Clinician generated segmentation of tumor and healthy tissue regions of interest (ROIs) on medical images is crucial for radiotherapy. However, interobserver segmentation variability has long been considered a significant detriment to the implementation of high-quality and consistent radiotherapy dose delivery. This has prompted the increasing development of automated segmentation approaches.