METTL3-mA-mediated TGF-β signaling promotes Fuchs endothelial corneal dystrophy via regulating corneal endothelial-to-mesenchymal transition.

Fuchs endothelial corneal dystrophy (FECD) is the leading cause of vision-threatening corneal endothelial dystrophy without pharmacologic treatments. Corneal endothelial-mesenchymal transition (cEndMT), a specific cellular phenotypic transition, is implicated in the vicious cycle in FECD pathogenesis. Here, we investigated the reversible epigenetic regulation of N-methyladenosine (mA) during cEndMT process and FECD progression.

Challenges and considerations in non-inferiority trials: a narrative review from statisticians' perspectives.

Background And Objective: Non-inferiority (NI) study is a popular randomized controlled trial design that aims to demonstrate whether a test treatment, considering its auxiliary benefits, is not unacceptably worse compared to a standard active control treatment. There is extensive work in the literature that discusses NI trials' merits, issues, and how certain clinical and statistical challenges can be addressed. Here, we are aimed to provide a narrative review of NI studies in terms of its design considerations, potential issues, and corresponding solutions from the perspectives of biostatisticians.

Genomic Landscapes of Early-Onset Versus Average-Onset Colorectal Cancer Populations.

Background: Rates of early-onset colorectal cancer (eoCRC), defined as disease diagnosed at <50 years of age, are increasing. The incidence and spectrum of somatic and pathogenic germline variants (PGV) in this population are not well understood.

Methods: This cross-sectional study leveraged Tempus' clinicogenomic database, including de-identified records of patients diagnosed with CRC between 2000-2022, to analyze and compare eoCRC and average-onset colorectal cancer (aoCRC, disease diagnosed ≥50 years of age) patients.

P2DFlow: A Protein Ensemble Generative Model with SE(3) Flow Matching.

Biological processes, functions, and properties are intricately linked to the ensemble of protein conformations rather than being solely determined by a single stable conformation. In this study, we developed P2DFlow, a generative model based on SE(3) flow matching, to predict the structural ensembles of proteins. We specifically designed a valuable prior for the flow process and enhanced the model's ability to distinguish each intermediate state by incorporating an additional dimension to describe the ensemble data, which can reflect the physical laws governing the distribution of ensembles so that the prior knowledge can effectively guide the generation process.

Observed different impacts of potential tree restoration on local surface and air temperature.

Tree restoration can cool or warm the local climate through biophysical processes. However, the magnitude of these effects remains unconstrained at large scales, as most previous observational studies rely on land surface temperature (Ts) rather than the more policy-relevant air temperature (Ta). Using satellite observations, we show that Ta responds to tree cover change at only 15-30% of the magnitude observed in Ts.

The association of physical activity with survival in colon cancer versus a matched general population: Data from Cancer and Leukemia Group B 89803 and 80702 (Alliance).

Background: Colon cancer patients have inferior overall survival than a matched general population (MGP). It is unknown if physical activity is associated with a reduction in this survival disparity.

Methods: Data were analyzed from two National Cancer Institute-sponsored postoperative treatment trials in stage III colon cancer, Cancer and Leukemia Group B (CALGB) 89803 and 80702, with 2876 patients who self-reported physical activity.

Optimizing the Host Niche to Fuel Cleft Lip Muscle Regeneration.

Objective: Lip muscle reconstruction is a key strategy for cleft lip repair, but the outcome of muscle regeneration is suboptimal. The lack of relevant models restricts studies on cleft lip muscle regeneration.

Design: In this study, we developed an animal xenograft model by transplanting muscle samples from patients with cleft lip into different host sites in immunodeficient mice.

Altered relaxation and Mitochondria-Endoplasmic Reticulum Contacts Precede Major (Mal)adaptations in Aging Skeletal Muscle and are Prevented by Exercise.

Sarcopenia, or age-related muscle dysfunction, contributes to morbidity and mortality. Besides decreases in muscle force, sarcopenia is associated with atrophy and fast-to-slow fiber type switching, which is typically secondary to denervation in humans and rodents. However, very little is known about cellular changes preceding these important (mal)adaptations.

Minimal Residual Disease-Based End Point for Accelerated Assessment of Clinical Trials in Multiple Myeloma: A Pooled Analysis of Individual Patient Data From Multiple Randomized Trials.

Purpose: Newly approved drugs and combinations treating multiple myeloma (MM) have resulted in substantial improvements in patients' survival. To deliver rapid access to newer therapies, an earlier end point to expedite clinical trials is needed. Our objective was to evaluate the minimal residual disease-negative complete response (MRD-CR) as an intermediate end point for progression-free survival (PFS) and overall survival (OS) in newly diagnosed (ND) transplant-eligible (NDTE) patients, ND transplant-ineligible (NDTinE) patients, and patients with relapsed/refractory (RR) MM.

Explore the possible influence of Sjogren's syndrome on thyroid cancer: A literature data mining and meta-analysis.

Objectives: To explore the potential influence of Sjogren's syndrome (SS) on thyroid cancer (TC).

Methods: First, a literature data mining (LDM) approach was used to reconstruct functional pathways connecting SS and TC. A meta-analysis was then performed to examine the expression changes of genes mediated by SS using 16 TC case/control expression datasets, with results validated through the TCGA/GTEx dataset.

A cross-sectional study exploring the predictors of herpes zoster vaccination for people aged over 50 years old in Chaoyang district, Beijing.

Background: Vaccination is an effective measure to prevent herpes zoster and its related complications. The coverage of herpes zoster vaccination is extremely low in China, and there is a notable lack of research investigating the barriers to promoting the herpes zoster vaccine in China.

Objectives: This study aims to survey the status of herpes zoster (HZ) vaccination and its associated factors among individuals aged 50 years and older, it also seeks to identify the barriers to vaccination and dissemination, thereby providing a scientific foundation for enhancing the vaccination rate of herpes zoster.

Persistent lipoprotein(a) exposure and its association with clinical outcomes after acute myocardial infarction: a longitudinal cohort study.

Aims: To assess the link between persistent lipoprotein(a) [Lp(a)] exposure levels and clinical outcomes in patients with acute myocardial infarction (AMI).

Methods: This longitudinal cohort study included 1131 AMI patients, categorizing persistent Lp(a) exposure based on measurements at admission and after 1 year. Patients were segmented into four groups using a 300 mg/L Lp(a) threshold: (1) persistent low Lp(a) (low - low); (2) fortified Lp(a) (low - high); (3) attenuated Lp(a) (high - low); and (4) persistent high Lp(a) (high - high).

Nonnegligible cascading impacts of global urban expansion on net primary productivity.

Accelerated global urban expansion not only directly occupies surrounding ecosystems, but also induces cascading losses of natural vegetation elsewhere through cropland displacement. Yet, how such effects alter the net primary productivity (NPP) worldwide remains unclear. Here, we quantified the direct and cascading impacts of global urban expansion on terrestrial NPP from 1992 to 2020 and projected the impacts under the shared socioeconomic pathways framework by 2100.

Lack of Hierarchical Survival Prognosis in AJCC Staging for Colon and Rectal Cancer-Implications for Future Summary Stage Classification.

Background: Current American Joint Committee on Cancer (AJCC) staging for colorectal cancer utilizes TNM framework groups disease based on extent and provides prognostic information, ideally with a hierarchical logic. We sought to evaluate survival as a function of stage within the 8 edition AJCC staging system for colon and rectal cancer.

Methods: Patients with primary colon or rectal cancer diagnosed 2010-2016 were identified from the National Cancer Database (NCDB).

Correlation analysis of key genes and immune infiltration in visceral adipose tissue and subcutaneous adipose tissue of patients with type 2 diabetes in women.

Immune cell infiltration into adipose tissue (AT) is a key factor in type 2 diabetes (T2DM). However, research on the impact of fat distribution on immune cells and immune responses in women is still lacking. This study used enrichment, protein-protein interaction network, immune cell infiltration, and correlation analysis to compare the similarities and differences between the transcriptome data of visceral AT (VAT) and subcutprotein-proteinaneous AT (SAT) obtained from the omprehensive database of gene expression in women with non-T2DM and T2DM.

DNA-Assisted Assays for Studying Lipid Transfer Between Membranes.

Extended-synaptotagmins (E-Syts) are proteins located on the endoplasmic reticulum (ER) that tether the ER to the plasma membrane (PM) and regulate their lipid homeostasis via its lipid transfer module, the synaptotagmin-like mitochondrial lipid-binding protein (SMP) domain. Here, we describe in vitro DNA nanostructure-assisted lipid transfer assays investigating how the SMP domain transports lipids between membranes and associates with the membranes to extract and release lipids. The lipid transfer signal was detected through fluorescence resonance energy transfer (FRET).

Benchmarks of Success in Radiotherapy versus Systemic Therapy National Clinical Trials Network (NCTN) Randomized Controlled Trials Sponsored by the National Cancer Institute (NCI).

Background: The National Clinical Trials Network (NCTN) is the largest government sponsored organization in the United States tasked with funding randomized controlled trials (RCTs) in oncology. It is unknown whether there are differences in study design by treatment modality. We evaluated differences in methodology between trials testing radiotherapy versus systemic therapy.

Optimal repetitive readout of single solid-state spins determined by Fisher information.

Quantum systems, including superconducting circuits, trapped ions, quantum dots, solid-state defects, etc., have achieved considerable advancements in readout fidelity. However, the widely used threshold method disregards the importance of temporal characteristics of the signal during continuous measurements, leading to information loss.

Establishment of a Raman microsphere-based immunochromatographic method for the combined detection of influenza A and B viruses and SARS-CoV-2 antigen on a single T-line.

A simple and rapid method based on Raman microsphere immunochromatography was developed in this study for the simultaneous detection of influenza A and B viruses and SARS-CoV-2 on a single test T-line. Three types of Raman microspheres with different Raman characteristics were used as the signal sources and were labelled with monoclonal antibodies against FluA, FluB and SARS-CoV-2, respectively. A mixture of antibodies containing anti-FluA monoclonal antibody, anti-FluB monoclonal antibody and anti-SARS-CoV-2 was sprayed on the detection line (T), and goat polyclonal antibody to chicken (IgY) encapsulated on the quality control line (C), for qualitative detection of these three viruses by the double antibody sandwich method.

Transcriptome Assembly at Single-Cell Resolution with Beaver.

Emerging single-cell RNA sequencing techniques (scRNA-seq) has enabled the study of cellular transcriptome heterogeneity, yet accurate reconstruction of full-length transcripts at single-cell resolution remains challenging due to high dropout rates and sparse coverage. While meta-assembly approaches offer promising solutions by integrating information across multiple cells, current methods struggle to balance consensus assembly with cell-specific transcriptional signatures. Here, we present Beaver, a cell-specific transcript assembler designed for short-read scRNA-seq data.

Circular RNA HIPK3 mediates epithelial-mesenchymal transition of retinal pigment epithelial cells by sponging multiple microRNAs.

Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells plays key roles in the pathogenesis of multiple vitreoretinal diseases, leading to profound and permanent vision loss. Circular RNAs (circRNAs) are widespread and functional endogenous RNAs that could regulate gene expression in eukaryotes. The functions of circRNAs in mediating EMT has been reported in several diseases.