Browse Articles

American alligators (Alligator mississippiensis) as wetland ecosystem carbon stock regulators

Ocean wave-driven covalent organic framework/ZnO heterostructure composites for piezocatalytic uranium extraction from seawater

An endoscopic ultrasound-based interpretable deep learning model and nomogram for distinguishing pancreatic neuroendocrine tumors from pancreatic cancer

Optimal life-cycle adaptation of coastal infrastructure under climate change

Assessment model of ozone pollution based on SHAP-IPSO-CNN and its application

Author Correction: Reprogramming the tumor immune microenvironment using engineered dual-drug loaded Salmonella

Distributed communication interference resource scheduling using the master-slave parallel scheduling genetic algorithm

Mechanism of stable lithium plating and stripping in a metal-interlayer-inserted anode-less solid-state lithium metal battery

Deep learning based decision-making and outcome prediction for adolescent idiopathic scoliosis patients with posterior surgery

MCT1 lactate transporter blockade re-invigorates anti-tumor immunity through metabolic rewiring of dendritic cells in melanoma

Effect of individual spinal muscle activities on upright posture using a human body finite element model

High-density lipoprotein nanoparticles spontaneously target to damaged renal tubules and alleviate renal fibrosis by remodeling the fibrotic niches

The PI4K2A gene positively regulates lipid synthesis in bovine mammary epithelial cells and attenuates the inhibitory effect of t10,c12-CLA on lipid synthesis

Short-term evolutionary implications of an introgressed size-determining supergene in a vulnerable population

Relationship between neutropenia caused by nanoliposomal irinotecan/fluorouracil/leucovorin and treatment outcomes in the NAPOLEON-2 study (NN-2301)

Abstract The relationship between nanoliposomal irinotecan/fluorouracil/leucovorin (NFF) treatment outcomes and neutropenia in patients with pancreatic cancer has not been thoroughly examined. Thus, we conducted a retrospective analysis of data from patients with pancreatic cancer who were treated with NFF to investigate this relationship. Neutropenia was assessed according to the Common Terminology Criteria for Adverse Events across three cutoffs: A (grade 0 versus grade 1–4), B (grades 0–1 versus 2–4), and C (grades 0–2 versus 3–4). The primary endpoint was overall survival (OS), and the secondary endpoints were overall response rate, progression-free survival (PFS), and relative dose intensity. Of the 161 patients, 93, 8, 22, 30, and 8 patients had neutropenia of grades 0, 1, 2, 3, and 4, respectively. The overall response rates differed significantly at cutoff C (p = 0.02), with the odds ratio for cutoff C being the highest, followed by cutoffs B and A. Significant differences in OS were observed at cutoffs A (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44–0.94; p = 0.02) and B (HR, 0.63; 95% CI, 0.43–0.92, p = 0.02). Similarly, PFS showed significant differences at cutoffs A and B (p < 0.01). NFF-induced neutropenia can be a useful prognostic factor for patients with pancreatic cancer.

Phosphorylation-dependent WRN-RPA interaction promotes recovery of stalled forks at secondary DNA structure

Interconnections between BDH1-plasma protein-type 2 diabetes Mellitus: a mediated mendelian randomization analysis using plasma proteomics

Helioseismic inference of the solar radiative opacity

A dynamic co-expression approach reveals Gins2 as a potential upstream modulator of HNSCC metastasis

Genetic coupling of enhancer activity and connectivity in gene expression control

Abstract Gene enhancers often form long-range contacts with promoters, but it remains unclear if the activity of enhancers and their chromosomal contacts are mediated by the same DNA sequences and recruited factors. Here, we study the effects of expression quantitative trait loci (eQTLs) on enhancer activity and promoter contacts in primary monocytes isolated from 34 male individuals. Using eQTL-Capture Hi-C and a Bayesian approach considering both intra- and inter-individual variation, we initially detect 19 eQTLs associated with enhancer-eGene promoter contacts, most of which also associate with enhancer accessibility and activity. Capitalising on these shared effects, we devise a multi-modality Bayesian strategy, identifying 629 “trimodal QTLs” jointly associated with enhancer accessibility, eGene promoter contact, and gene expression. Causal mediation analysis and CRISPR interference reveal causal relationships between these three modalities. Many detected QTLs overlap disease susceptibility loci and influence the predicted binding of myeloid transcription factors, including SPI1, GABPB and STAT3. Additionally, a variant associated with PCK2 promoter contact directly disrupts a CTCF binding motif and impacts promoter insulation from downstream enhancers. Jointly, our findings suggest an inherent genetic coupling of enhancer activity and connectivity in gene expression control relevant to human disease and highlight the regulatory role of genetically determined chromatin boundaries.