A unified analysis of atlas single-cell data.

Recent efforts to generate atlas-scale single-cell data provide opportunities for joint analysis across tissues and modalities. Existing methods use cells as the reference unit, hindering downstream gene-based analysis and removing genuine biological variation. Here we present GIANT, an integration method designed for atlas-scale gene analysis across cell types and tissues.

scDOT: optimal transport for mapping senescent cells in spatial transcriptomics.

The low resolution of spatial transcriptomics data necessitates additional information for optimal use. We developed scDOT, which combines spatial transcriptomics and single cell RNA sequencing to improve the ability to reconstruct single cell resolved spatial maps and identify senescent cells. scDOT integrates optimal transport and expression deconvolution to learn non-linear couplings between cells and spots and to infer cell placements.

Vietnamese sixth graders' mathematical communication competency developed by teaching fraction topics using the 5E model.

The 5E, an exploratory instructional model with growing popularity in current learner-centered educational practices, aims to develop learners' competencies. The study aims to evaluate the effectiveness of teaching fractions using the 5E instructional model to develop students' mathematical communication competency (MCC). The researchers used mixed methods with data triangulation in a 38-student experiment group (EG) who learned with the 5E model and a 41-student control group (CG) using traditional learning approaches to clarify the impact of the 5E model on the development of MCC, academic performance and learning attitude among learners.

The Cytochrome P450 2C8*3 Variant (rs11572080) Is Associated with Improved Asthma Symptom Control in Children and Altered Lipid Mediator Production and Inflammatory Response in Human Bronchial Epithelial Cells.

This study investigated an association between the cytochrome P450 (CYP) 2C8*3 polymorphism with asthma symptom control in children and changes in lipid metabolism and pro-inflammatory signaling by human bronchial epithelial cells (HBECs) treated with cigarette smoke condensate (CSC). CYP genes are inherently variable in sequence, and while such variations are known to produce clinically relevant effects on drug pharmacokinetics and pharmacodynamics, the effects on endogenous substrate metabolism and associated physiologic processes are less understood. In this study, CYP2C8*3 was associated with improved asthma symptom control among children: Mean asthma control scores were 3.

Mechanisms and Consequences of Variable TRPA1 Expression by Airway Epithelial Cells: Effects of Genotype and Environmental Agonists on Cellular Responses to Pollutants and Asthma.

Background: Transient receptor potential ankyrin-1 [transient receptor potential cation channel subfamily A member 1 (TRPA1)] and vanilloid-1 [transient receptor potential cation channel subfamily V member 1 (TRPV1)] detect inhaled irritants, including air pollutants and have roles in the development and exacerbation of asthma.

Objectives: This study tested the hypothesis that increased expression of TRPA1, stemming from expression of the loss-of-function (I585V; rs8065080) polymorphic variant by airway epithelial cells may explain prior observations of worse asthma symptom control among children with the I585I/V genotype, by virtue of sensitizing epithelial cells to particulate materials and other TRPA1 agonists.

Methods: TRP agonists, antagonists, small interfering RNA (siRNA), a nuclear factor kappa light chain enhancer of activated B cells (NF-) pathway inhibitor, and kinase activators and inhibitors were used to modulate TRPA1 and TRPV1 expression and function.

A deep manifold-regularized learning model for improving phenotype prediction from multi-modal data.

The phenotypes of complex biological systems are fundamentally driven by various multi-scale mechanisms. Multi-modal data, such as single cell multi-omics data, enables a deeper understanding of underlying complex mechanisms across scales for phenotypes. We developed an interpretable regularized learning model, deepManReg, to predict phenotypes from multi-modal data.

Dynamic Expression of Transient Receptor Potential Vanilloid-3 and Integrated Signaling with Growth Factor Pathways during Lung Epithelial Wound Repair following Wood Smoke Particle and Other Forms of Lung Cell Injury.

Prior studies revealed increased expression of the transient receptor potential vanilloid-3 (TRPV3) ion channel after wood smoke particulate matter (WSPM) treatment of human bronchial epithelial cells (HBECs). TRPV3 attenuated pathologic endoplasmic reticulum stress and cytotoxicity mediated by transient receptor potential ankyrin-1. Here, the basis for how TRPV3 expression is regulated by cell injury and the effects this has on HBEC physiology and WSPM-induced airway remodeling in mice was investigated.

ECMarker: interpretable machine learning model identifies gene expression biomarkers predicting clinical outcomes and reveals molecular mechanisms of human disease in early stages.

Motivation: Gene expression and regulation, a key molecular mechanism driving human disease development, remains elusive, especially at early stages. Integrating the increasing amount of population-level genomic data and understanding gene regulatory mechanisms in disease development are still challenging. Machine learning has emerged to solve this, but many machine learning methods were typically limited to building an accurate prediction model as a 'black box', barely providing biological and clinical interpretability from the box.

Varmole: a biologically drop-connect deep neural network model for prioritizing disease risk variants and genes.

Summary: Population studies such as genome-wide association study have identified a variety of genomic variants associated with human diseases. To further understand potential mechanisms of disease variants, recent statistical methods associate functional omic data (e.g.

Transient Receptor Potential Ankyrin-1 and Vanilloid-3 Differentially Regulate Endoplasmic Reticulum Stress and Cytotoxicity in Human Lung Epithelial Cells After Pneumotoxic Wood Smoke Particle Exposure.

This study investigated the roles of transient receptor potential (TRP) ankyrin-1 (TRPA1) and TRP vanilloid-3 (TRPV3) in regulating endoplasmic reticulum stress (ERS) and cytotoxicity in human bronchial epithelial cells (HBECs) treated with pneumotoxic wood smoke particulate matter (WSPM) and chemical agonists of each channel. Functions of TRPA1 and TRPV3 in pulmonary epithelial cells remain largely undefined. This study shows that TRPA1 activity localizes to the plasma membrane and endoplasmic reticulum (ER) of cells, whereas TRPV3 resides primarily in the ER.

Multiview learning for understanding functional multiomics.

The molecular mechanisms and functions in complex biological systems currently remain elusive. Recent high-throughput techniques, such as next-generation sequencing, have generated a wide variety of multiomics datasets that enable the identification of biological functions and mechanisms via multiple facets. However, integrating these large-scale multiomics data and discovering functional insights are, nevertheless, challenging tasks.

Wood Smoke Particles Stimulate MUC5AC Overproduction by Human Bronchial Epithelial Cells Through TRPA1 and EGFR Signaling.

Mucus hypersecretion is a pathological feature of acute inflammatory and chronic obstructive pulmonary diseases. Exposure to air pollutants can be a cause of pathological mucus overproduction, but mechanisms by which different forms of air pollutants elicit this response are not fully understood. In this study, particulate matter (PM) generated from burning pine wood and other types of biomass was used to determine mechanisms by which these forms of PM stimulate mucin gene expression and secretion by primary human bronchial epithelial cells (HBECs).

ManiNetCluster: a novel manifold learning approach to reveal the functional links between gene networks.

Background: The coordination of genomic functions is a critical and complex process across biological systems such as phenotypes or states (e.g., time, disease, organism, environmental perturbation).

Lambert-Eaton myasthenic syndrome and merkel cell carcinoma.

Lambert-Eaton myasthenic syndrome (LEMS) is an antibody-mediated disorder of the neuromuscular junction that is most commonly diagnosed in association with small cell lung carcinoma (SCLC). Small cell lung carcinoma is histologically similar to the aggressive cutaneous neuroendocrine malignancy Merkel cell carcinoma (MCC). We provide a full report and longitudinal clinical follow-up of a case of LEMS occurring with MCC.

Negative reinforcement impairs overnight memory consolidation.

Post-learning sleep is beneficial for human memory. However, it may be that not all memories benefit equally from sleep. Here, we manipulated a spatial learning task using monetary reward and performance feedback, asking whether enhancing the salience of the task would augment overnight memory consolidation and alter its incorporation into dreaming.

Overnight Sleep Enhances Hippocampus-Dependent Aspects of Spatial Memory.

Study Objectives: Several studies have now demonstrated that spatial information is processed during sleep, and that posttraining sleep is beneficial for human navigation. However, it remains unclear whether the effects of sleep are primarily due to consolidation of cognitive maps, or alternatively, whether sleep might also affect nonhippocampal aspects of navigation (e.g.

Fever control in septic shock: beneficial or harmful?

The beneficial effects of interventions to control fever in sepsis are controversial. We investigated whether the use of acetaminophen and external cooling is beneficial to control fever in septic shock. We studied 24 fasted, anesthetized, invasively monitored, mechanically ventilated female sheep (27.

Use of low tidal volume in septic shock may decrease severity of subsequent acute lung injury.

Recent studies have indicated that protective lung strategies may improve outcomes in acute lung injury. We hypothesized that the use of a lower tidal volume early during septic shock may protect against the subsequent development of acute lung injury. Fourteen fasted, anesthetized, invasively monitored, mechanically ventilated, female sheep (26.