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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.
Multistage deep learning methods for automating radiographic sharp score prediction in rheumatoid arthritis
Data-driven exploration of weak coordination microenvironment in solid-state electrolyte for safe and energy-dense batteries
Binocular stereo vision-based relative positioning algorithm for drone swarm
A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer
Abstract While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on “bystander” genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed. Combining these approaches, we propose a class of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes located in commonly amplified regions, yet expressed at lower levels than expected by their copy number, and toxic when overexpressed. We validate RBM14 as an ARGOS gene in lung and breast cancer cells, and suggest a toxicity mechanism involving altered DNA damage response and STING signaling. We additionally observe increased patient survival in a radiation-treated cancer cohort with RBM14 amplification.