stImage: a versatile framework for optimizing spatial transcriptomic analysis through customizable deep histology and location informed integration.

Spatial transcriptomics (ST) integrates gene expression data with the spatial organization of cells and their associated histology, offering unprecedented insights into tissue biology. While existing methods incorporate either location-based or histology-informed information, none fully synergize gene expression, histological features, and precise spatial coordinates within a unified framework. Moreover, these methods often exhibit inconsistent performance across diverse datasets and conditions.

Protective role of epithelial deoxyhypusine synthase in colorectal carcinogenesis caused by deletion of the adenomatous polyposis coli gene.

Mutations in the adenomatous polyposis coli (APC) gene lead to the formation of adenomatous polyps in the colon that can evolve into carcinoma. We have reported that deoxyhypusine synthase (DHPS), the rate-limiting enzyme for the synthesis of the amino acid hypusine on the eukaryotic translation initiation factor 5A, plays a major role in intestinal homoeostasis. Here, we investigated the role of hypusination in sporadic colorectal cancer (CRC).

Genetic analysis in African ancestry populations reveals genetic contributors to lung cancer susceptibility.

Striking disparities in lung cancer exist, with Black/African American individuals disproportionately affected by lung cancer, yet the genetic architecture in African ancestry individuals is poorly understood. We aimed to address this by performing a comprehensive genetic association study of lung cancer, incorporating local ancestry, across 6,490 African ancestry individuals (2,390 individuals with lung cancer and 4,100 control subjects). We identified a single genome-wide significant (p < 5 × 10) locus, 15q25.

Machine Learning-Assisted Prediction of Mercury Removal Efficiency of Carbon-Based Adsorbents.

Adsorbent injection is the most promising technology for solving anthropogenic mercury (mainly Hg) emission from stationary sources. Carbon-based adsorbents have strong potential for Hg removal due to their high specific surface area and abundant functional groups. However, traditional experimental methods focus on a single adsorbent under specific mercury removal conditions, making it difficult to obtain universal influencing laws and optimal preparation methods for the adsorbents.

Preparation of Foamed Ceramic from Cr Slag and MSWI Fly Ash and Its Cr Leaching Inhibition.

The sustainable utilization of solid waste is crucial for environmental protection. This work investigates the fabrication of foamed ceramics from Cr slag and municipal solid waste incineration (MSWI) fly ash, focusing on the effects of three inhibitors-NHSOH, ZnO·TiO, and (NH)HPO-on material properties and Cr leaching behavior. Experimental analysis, chemical thermodynamic calculations, and material characterization were all employed.

Glo-In-One-v2: holistic identification of glomerular cells, tissues, and lesions in human and mouse histopathology.

Purpose: Segmenting intraglomerular tissue and glomerular lesions traditionally depends on detailed morphological evaluations by expert nephropathologists, a labor-intensive process susceptible to interobserver variability. Our group previously developed the Glo-In-One toolkit for integrated glomerulus detection and segmentation. We leverage the Glo-In-One toolkit to version 2 (Glo-In-One-v2), which adds fine-grained segmentation capabilities.

Human Physiologic Responses to Insulin in Indigenous Americans Identify a Metabolic Susceptibility Profile Linked to Diabetes.

Objective: To identify metabolic signatures of insulin action/secretion in Indigenous Americans (IAs) and their association with diabetes.

Research Design And Methods: We defined circulating metabolomic signatures of insulin action/secretion in 446 IAs, including glucose disposal rate during low-dose insulin clamp (Mlow) and endogenous glucose production (EGP) during insulin infusion (suppression of hepatic glucose production). We then determined associations of these metabolic scores with glucose tolerance (in a separate set of ∼700 IAs) and diabetes/metabolic risk in ∼2,000 individuals (from Coronary Artery Risk Development in Young Adults [CARDIA] study).

Low-Rank Fine-Tuning Meets Cross-modal Analysis: A Robust Framework for Age-Related Macular Degeneration Categorization.

Age-related macular degeneration (AMD) is a prevalent retinal degenerative disease among the elderly and is a major cause of irreversible vision loss worldwide. Although color fundus photography (CFP) and optical coherence tomography (OCT) are widely used for AMD diagnosis, information from a single modal is inadequate to fully capture the complex pathological features of AMD. To address this, this study proposes an innovative multi-modal deep learning framework that fine-tunes pre-trained single-modal retinal models for efficient application in multi-modal AMD categorization tasks.

Beta 2 adrenergic receptor gene methylation activates innate lymphoid cells to drive hypertension in lymphocyte deficient hosts.

Aims: T cells contribute to hypertension; however, hypertension occurs in settings of T cell deficiency.

Methods And Results: We studied two colonies of T/B cell-deficient RAG-1-/- mice with disparate responses to angiotensin II, being one protected from blood pressure increase and the other one responsive. This difference depends on the capability of hypertensive RAG-1-/- mice to expand natural killer and innate lymphoid cells (NK/ILCs) that produce pro-hypertensive cytokines.

Segment Anything Model (SAM) for Digital Pathology: Assess Zero-shot Segmentation on Whole Slide Imaging.

Unlabelled: The segment anything model (SAM) was released as a foundation model for image segmentation. The promptable segmentation model was trained by over 1 billion masks on 11M licensed and privacy-respecting images. The model supports zero-shot image segmentation with various segmentation prompts (e.

HATs: Hierarchical Adaptive Taxonomy Segmentation for Panoramic Pathology Image Analysis.

Panoramic image segmentation in computational pathology presents a remarkable challenge due to the morphologically complex and variably scaled anatomy. For instance, the intricate organization in kidney pathology spans multiple layers, from regions like the cortex and medulla to functional units such as glomeruli, tubules, and vessels, down to various cell types. In this paper, we propose a novel Hierarchical Adaptive Taxonomy Segmentation (HATs) method, which is designed to thoroughly segment panoramic views of kidney structures by leveraging detailed anatomical insights.

PrPSeg: Universal Proposition Learning for Panoramic Renal Pathology Segmentation.

Understanding the anatomy of renal pathology is crucial for advancing disease diagnostics, treatment evaluation, and clinical research. The complex kidney system comprises various components across multiple levels, including regions (cortex, medulla), functional units (glomeruli, tubules), and cells (podocytes, mesangial cells in glomerulus). Prior studies have predominantly overlooked the intricate spatial interrelations among objects from clinical knowledge.

Molecular architecture of human atherosclerosis revealed through integrative human genetics.

Current genetic discovery methods are largely restricted to profiling circulating molecules or genetic architecture, limited in use of tissue-based molecular genetics to identify pathogenic and therapeutic targets. Here, we leverage a multi-level genetic discovery platform integrating population-level proteomics with functional genomic analyses based on human coronary artery tissue to reveal determinants of coronary disease susceptibility. Using aptamer-based proteomics (~7,000 aptamers) across ~3,000 individuals, we first identified the circulating proteome of prevalent and incident coronary artery calcium (CAC), a sensitive marker of subclinical coronary artery disease (CAD), with causal implication in calcified plaque formation or disease phenotypes via parallel genetic approaches (Mendelian randomization, MR) and proteome-wide association (PWAS).

Dynamic responses to rejection in the transplanted human heart revealed through spatial transcriptomics.

Allograft rejection following solid-organ transplantation is a major cause of graft dysfunction and mortality. Current approaches to diagnosis rely on histology, which exhibits wide diagnostic variability and lacks access to molecular phenotypes that may stratify therapeutic response. Here, we leverage image-based spatial transcriptomics at sub-cellular resolution in longitudinal human cardiac biopsies to characterize transcriptional heterogeneity in 62 adult and pediatric heart transplant (HT) recipients during and following histologically-diagnosed rejection.

Enhanced Acidic CO-to-C Reduction via Ionic Liquid Layer Modification.

Acidic CO electroreduction reaction (CORR) garners significant attention as a promising approach for cutting carbon density, as it effectively mitigates CO loss by suppressing carbonate species formation. Unfortunately, achieving efficient multi-carbon products (C) production in acidic media remains challenging due to two main limitations: weak CO adsorption on Cu sites and competitive H* adsorption caused by the high concentration protons (H). To overcome these challenges, a cation-anion-modification strategy is proposed using an ionic liquid layer-1-Propyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([PMIM][NTf])-on Cu surface.

Does Palatoplasty Technique Impact Resolution of Eustachian Tube Dysfunction?

ObjectiveTo determine whether palatoplasty technique affects the resolution of eustachian tube dysfunction and postoperative speech outcomes in children with cleft palate (CP).DesignRetrospective cohort.SettingMultidisciplinary cleft and craniofacial clinic at a tertiary care center.

Combining stable isotopes and multi-elements with machine learning chemometric models to identify the geographical origins of Tetrastigma hemsleyanum Diels et Gilg.

Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum) is an edible plant with considerable medicinal properties, the quality of which varies depending on its origin. Therefore economically motivated adulteration has emerged.

Outcome Analysis of Parathyroid Gland Auto-transplantation in Pediatric Patients: A Retrospective Review.

Parathyroid gland (PG) auto-transplantation is performed to preserve the function of de-vascularized or unintentionally removed PGs, however, little has been published about the technique and outcomes in children. In our study, we aimed to present the results of PG auto-transplantation in children undergoing thyroidectomy or parathyroidectomy at a tertiary single institution. A retrospective review identified 14 patients (<18 years of age) who underwent PG auto-transplantation from January 2000 to December 2022.

ET-3/ETBR Mediates Na-Activated Immune Signaling and Kidney Lymphatic Dynamics.

Background: Lymphatic collecting vessels in the kidney are critical in clearing interstitial fluid, macromolecules, and infiltrating immune cells. Dysfunction of the lymphatic vessels can disrupt this process and exacerbate injury-associated inflammation in many disease conditions. We previously found that sodium accumulates within the kidney interstitium during proteinuric kidney injury and elevated sodium environments stimulate isolevuglandin production in antigen-presenting cells, stimulating T cells, and modulating inflammatory responses.

Hepatic Steatosis and Fibrosis, Cardiorespiratory Fitness, and Metabolic Mediators in the Community.

Background And Aims: Individuals with steatotic liver disease (SLD) are at high cardiovascular disease (CVD) risk, but approaches to characterise and mitigate this risk are limited. By investigating relations, and shared metabolic pathways, of hepatic steatosis/fibrosis and cardiorespiratory fitness (CRF), we sought to identify new avenues for CVD risk reduction in SLD.

Methods: In Framingham Heart Study (FHS) participants (N = 2722, age 54 ± 9 years, 53% women), vibration-controlled transient elastography (VCTE) was performed between 2016-2019 to assess hepatic steatosis (continuous attenuation parameter [CAP]) and fibrosis (liver fibrosis measure [LSM]).

Hypusination in intestinal epithelial cells protects mice from infectious colitis.

Enteropathogenic (EPEC) is a bacterium that causes attaching/effacing (A/E) lesions and serious diarrheal disease, a major health issue in developing countries. EPEC pathogenicity results from the effect of virulence factors and dysregulation of host responses. Polyamines, including spermidine, play a major role in intestinal homeostasis.

A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver.

Hepatic steatosis is a central phenotype in multi-system metabolic dysfunction and is increasing in parallel with the obesity pandemic. We use a translational approach integrating clinical phenotyping and outcomes, circulating proteomics, and tissue transcriptomics to identify dynamic, functional biomarkers of hepatic steatosis. Using multi-modality imaging and broad proteomic profiling, we identify proteins implicated in the progression of hepatic steatosis that are largely encoded by genes enriched at the transcriptional level in the human liver.

A metagenome-assembled genome inventory for children reveals early-life gut bacteriome and virome dynamics.

Existing microbiota databases are biased toward adult samples, hampering accurate profiling of the infant gut microbiome. Here, we generated a metagenome-assembled genome inventory for children (MAGIC) from a large collection of bulk and viral-like particle-enriched metagenomes from 0 to 7 years of age, encompassing 3,299 prokaryotic and 139,624 viral species-level genomes, 8.5% and 63.

Otolaryngologists Demonstrate Low Agreement on Pediatric Airway Inflammation Assessment.

Objectives: Microlaryngoscopy and bronchoscopy (MLB) are essential tools for evaluating airway inflammation, but the reliability of endoscopic assessments for this purpose remains unclear. The aim of this study was to assess surgeons' interrater reliability during endoscopic assessment of airway inflammation. The endoscopic factors used to determine overall airway inflammation were also assessed.

The reverse transsulfuration pathway affects the colonic microbiota and contributes to colitis in mice.

Cystathionine γ-lyase (CTH) is a critical enzyme in the reverse transsulfuration pathway, the major route for the metabolism of sulfur-containing amino acids, notably converting cystathionine to cysteine. We reported that CTH supports gastritis induced by the pathogen Helicobacter pylori. Herein our aim was to investigate the role of CTH in colonic inflammation.