Development and Validation of Multiparametric MRI-based Interpretable Deep Learning Radiomics Fusion Model for Predicting Lymph Node Metastasis and Prognosis in Rectal Cancer: A Two-center Study.

Rationale And Objectives: To develop interpretable machine learning models that utilize deep learning (DL) and radiomics based on multiparametric Magnetic resonance imaging (MRI) to predict preoperative lymph node (LN) metastasis in rectal cancer.

Materials And Methods: This retrospective study involved 286 cancer patients confirmed by histopathology from center 1 (Training set) and 66 patients from center 2 (External test set). Radiomics features were extracted from T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) sequences, whereas DL features were obtained using four models: MobileNet-V3-large, Inception-V3, ResNet50, and VGG16.

Enhancing transcription-replication conflict targets ecDNA-positive cancers.

Extrachromosomal DNA (ecDNA) presents a major challenge for cancer patients. ecDNA renders tumours treatment resistant by facilitating massive oncogene transcription and rapid genome evolution, contributing to poor patient survival. At present, there are no ecDNA-specific treatments.

Transcatheter Aortic-Valve Replacement for Asymptomatic Severe Aortic Stenosis.

Background: For patients with asymptomatic severe aortic stenosis and preserved left ventricular ejection fraction, current guidelines recommend routine clinical surveillance every 6 to 12 months. Data from randomized trials examining whether early intervention with transcatheter aortic-valve replacement (TAVR) will improve outcomes in these patients are lacking.

Methods: At 75 centers in the United States and Canada, we randomly assigned, in a 1:1 ratio, patients with asymptomatic severe aortic stenosis to undergo early TAVR with transfemoral placement of a balloon-expandable valve or clinical surveillance.

Soluble Tim-3 serves as a tumor prognostic marker and therapeutic target for CD8 T cell exhaustion and anti-PD-1 resistance.

Resistance to PD-1 blockade in onco-immunotherapy greatly limits its clinical application. T cell immunoglobulin and mucin domain containing-3 (Tim-3), a promising immune checkpoint target, is cleaved by ADAM10/17 to produce its soluble form (sTim-3) in humans, potentially becoming involved in anti-PD-1 resistance. Herein, serum sTim-3 upregulation was observed in non-small cell lung cancer (NSCLC) and various digestive tumors.

Enhancing homology-directed repair efficiency with HDR-boosting modular ssDNA donor.

Despite the potential of small molecules and recombinant proteins to enhance the efficiency of homology-directed repair (HDR), single-stranded DNA (ssDNA) donors, as currently designed and chemically modified, remain suboptimal for precise gene editing. Here, we screen the biased ssDNA binding sequences of DNA repair-related proteins and engineer RAD51-preferred sequences into HDR-boosting modules for ssDNA donors. Donors with these modules exhibit an augmented affinity for RAD51, thereby enhancing HDR efficiency across various genomic loci and cell types when cooperated with Cas9, nCas9, and Cas12a.

The symptoms evolution of long COVID‑19 (SE-LC19): a new patient-reported content valid instrument.

Background: The field of long COVID research is rapidly evolving, however, tools to assess and monitor symptoms and recovery of the disease are limited. The objective of the present study was to develop a new patient-reported outcomes instrument, the Symptoms Evolution of Long COVID‑19 (SE-LC19), and establish its content validity.

Methods: The 40-item SE-LC19 instrument was developed based on patient-relevant empirical evidence from scientific literature and clinical guidelines that reported symptoms specific to long COVID.

Preclinical evaluation of stereopure antisense oligonucleotides for allele-selective lowering of mutant .

Huntington's disease (HD) is an autosomal dominant disease caused by the expansion of cytosine-adenine-guanine (CAG) repeats in one copy of the gene (mutant HTT, mHTT). The unaffected gene encodes wild-type HTT (wtHTT) protein, which supports processes important for the health and function of the central nervous system. Selective lowering of mHTT for the treatment of HD may provide a benefit over nonselective HTT-lowering approaches, as it aims to preserve the beneficial activities of wtHTT.

Integrating Clinical Data and Radiomics and Deep Learning Features for End-to-End Delayed Cerebral Ischemia Prediction on Noncontrast CT.

Background And Purpose: Delayed cerebral ischemia is hard to diagnose early due to gradual, symptomless development. This study aimed to develop an automated model for predicting delayed cerebral ischemia following aneurysmal SAH on NCCT.

Materials And Methods: This retrospective study included 400 patients with aneurysmal SAH (156 with delayed cerebral ischemia) who underwent NCCT.

Adjusted Tumor Enhancement on Dual-Phase Cone-Beam CT: Predictor of Response and Overall Survival in Patients with Liver Malignancies Treated with Hepatic Artery Embolization.

The aim of this study was to examine the value of tumor enhancement parameters on dual-phase cone-beam CT (CBCT) in predicting initial response, local progression-free survival (L-PFS) and overall survival (OS) following hepatic artery embolization (HAE). Between Feb 2016 and Feb 2023, 13 patients with 29 hepatic tumors treated with HAE were analyzed. Pre- and post-embolization, subtracted CBCTs were performed, and tumor enhancement parameters were measured, resulting in three parameters: pre-embolization Adjusted Tumor Enhancement (pre-ATE), post-embolization ATE and the difference between pre- and post-ATE (∆ATE).

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).

Effect of Isocaloric, Time-Restricted Eating on Body Weight in Adults With Obesity : A Randomized Controlled Trial.

Background: Time-restricted eating (TRE) lowers body weight in many studies. Whether TRE induces weight loss independent of reductions in calorie intake, as seen in rodent studies, is unknown.

Objective: To determine the effect of TRE versus a usual eating pattern (UEP) on body weight in the setting of stable caloric intake.

Peripheral Immune Profiles Predict ALS Progression in an Age- and Sex-Dependent Manner.

Background And Objectives: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease whose pathobiology associates with peripheral blood immune cell levels and activation patterns in an age and sex-dependent manner. This study's objective was to identify immune profile associations with ALS progression, whether the associations are age and sex-specific, and whether immune profiles can predict a future disease course.

Methods: Flow cytometry immune profiles (a combination of 22 peripheral blood immune markers) were generated for 241 participants with ALS and linked to ALS progression, using progression-free survival, which is a composite combining the revised ALS Functional Rating Scale and survival.

Immunoproteasomal Processing of IsoLG-Adducted Proteins Is Essential for Hypertension.

Background: Hypertension is characterized by CD8 (cluster differentiation 8) T cell activation and infiltration into peripheral tissues. CD8 T cell activation requires proteasomal processing of antigenic proteins. It has become clear that isoLG (isolevuglandin)-adduced peptides are antigenic in hypertension; however, IsoLGs inhibit the constitutive proteasome.

Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer.

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS.

LXRα Promotes Abdominal Aortic Aneurysm Formation Through UHRF1 Epigenetic Modification of miR-26b-3p.

Background: Abdominal aortic aneurysm (AAA) is a severe aortic disease without effective pharmacological approaches. The nuclear hormone receptor LXRα (liver X receptor α), encoded by the gene, serves as a critical transcriptional mediator linked to several vascular pathologies, but its role in AAA remains elusive.

Methods: Through integrated analyses of human and murine AAA gene expression microarray data sets, we identified as a candidate gene regulating AAA formation.

The burden of mental disorders in Asian countries, 1990-2019: an analysis for the global burden of disease study 2019.

Mental disorders are the leading contributors to the globally nonfatal burden of disease. This study was aimed to estimate the burden of mental disorders in Asian countries. Based on GBD 2019, the prevalence and disability-adjusted life of years (DALYs) rates with 95% uncertainty intervals (UI) were estimated in Asian countries.

Comparative prognostic importance of measures of left atrial structure and function in non-ischaemic dilated cardiomyopathy.

Aims: This study aimed to compare the association between measures of left atrial (LA) structure and function, derived from cardiovascular magnetic resonance (CMR), with cardiovascular death or non-fatal heart failure events in patients with non-ischaemic dilated cardiomyopathy (DCM).

Methods And Results: CMR studies of 580 prospectively recruited patients with DCM in sinus rhythm [median age 54 (interquartile range 44-64) years, 61% men, median left ventricular ejection fraction 42% (30-51%)] were analysed for measures of LA structure [LA maximum volume index (LAVImax) and LA minimum volume index (LAVImin)] and function (LA emptying fraction, LA reservoir strain, LA conduit strain (LACS), and LA booster strain]. Over a median follow-up of 7.

Approaches for Performance Verification Toward Standardization of Peripheral Blood Regulatory T-Cell Detection by Flow Cytometry.

Context.—: Regulatory T-cell (Treg) detection in peripheral blood, based on flow cytometry, is invaluable for diagnosis and treatment of immune-mediated diseases. However, there is a lack of reliable methods to verify the performance, which is pivotal toward standardization of the Tregs assay.

Carbonylation of Runx2 at K176 by 4-Hydroxynonenal Accelerates Vascular Calcification.

Background: Vascular calcification, which is characterized by calcium deposition in arterial walls and the osteochondrogenic differentiation of vascular smooth muscle cells, is an actively regulated process that involves complex mechanisms. Vascular calcification is associated with increased cardiovascular adverse events. The role of 4-hydroxynonenal (4-HNE), which is the most abundant stable product of lipid peroxidation, in vascular calcification has been poorly investigated.