A transcription factor network regulates proliferation of glomerular endothelial cells in diabetic kidney disease.

The maintenance of a healthy epithelial-endothelial juxtaposition requires cross-talk within glomerular cellular niches. We sought to understand the spatially-anchored regulation and transition of endothelial and mesangial cells from health to injury in DKD. From 74 human kidney samples, an integrated multi-omics approach was leveraged to identify cellular niches, cell-cell communication, cell injury trajectories, and regulatory transcription factor (TF) networks in glomerular capillary endothelial (EC-GC) and mesangial cells.

COCONUT 2.0: a comprehensive overhaul and curation of the collection of open natural products database.

The COCONUT (COlleCtion of Open Natural prodUcTs) database was launched in 2021 as an aggregation of openly available natural product datasets and has been one of the biggest open natural product databases since. Apart from the chemical structures of natural products, COCONUT contains information about names and synonyms, species and organism parts in which the natural product has been found, geographic information about where the respective sample has been collected and literature references, where available. COCONUT is openly accessible at https://coconut.

Perioperative Acute Kidney Injury: Diagnosis, Prediction, Prevention, and Treatment.

In this review, the authors define acute kidney injury in the perioperative setting, describe the epidemiologic burden, discuss procedure-specific risk factors, detail principles of management, and highlight areas of ongoing controversy and research.

Attenuated kidney oxidative metabolism in young adults with type 1 diabetes.

BACKGROUNDIn type 1 diabetes (T1D), impaired insulin sensitivity may contribute to the development of diabetic kidney disease (DKD) through alterations in kidney oxidative metabolism.METHODSYoung adults with T1D (n = 30) and healthy controls (HCs) (n = 20) underwent hyperinsulinemic-euglycemic clamp studies, MRI, 11C-acetate PET, kidney biopsies, single-cell RNA-Seq, and spatial metabolomics to assess this relationship.RESULTSParticipants with T1D had significantly higher glomerular basement membrane (GBM) thickness compared with HCs.

Voluntary sector specialist service provision and commissioning for victim-survivors of sexual violence: results from two national surveys in England.

Background: In England, voluntary sector specialist (VSS) services are central to supporting victim-survivors of sexual violence (SV). However, empirical evidence is lacking about the scope, range and effectiveness of VSS provision for SV in England.

Objectives: To undertake national surveys to map SV VSS service provision and describe arrangements for funding and commissioning.

Deciphering Metabolic Pathways in High-Seeding-Density Fed-Batch Processes for Monoclonal Antibody Production: A Computational Modeling Perspective.

Due to their high specificity, monoclonal antibodies (mAbs) have garnered significant attention in recent decades, with advancements in production processes, such as high-seeding-density (HSD) strategies, contributing to improved titers. This study provides a thorough investigation of high seeding processes for mAb production in Chinese hamster ovary (CHO) cells, focused on identifying significant metabolites and their interactions. We observed high glycolytic fluxes, the depletion of asparagine, and a shift from lactate production to consumption.

Ontology-based modeling, integration, and analysis of heterogeneous clinical, pathological, and molecular kidney data for precision medicine.

Many data resources generate, process, store, or provide kidney related molecular, pathological, and clinical data. Reference ontologies offer an opportunity to support knowledge and data integration. The Kidney Precision Medicine Project (KPMP) team contributed to the representation and addition of 329 kidney phenotype terms to the Human Phenotype Ontology (HPO), and identified many subcategories of acute kidney injury (AKI) or chronic kidney disease (CKD).

Combination therapy for kidney disease in people with diabetes mellitus.

Diabetic kidney disease (DKD), defined as co-existing diabetes and chronic kidney disease in the absence of other clear causes of kidney injury, occurs in approximately 20-40% of patients with diabetes mellitus. As the global prevalence of diabetes has increased, DKD has become highly prevalent and a leading cause of kidney failure, accelerated cardiovascular disease, premature mortality and global health care expenditure. Multiple pathophysiological mechanisms contribute to DKD, and single lifestyle or pharmacological interventions have shown limited efficacy at preserving kidney function.

Integrated multiomics implicates dysregulation of ECM and cell adhesion pathways as drivers of severe COVID-associated kidney injury.

COVID-19 has been a significant public health concern for the last four years; however, little is known about the mechanisms that lead to severe COVID-associated kidney injury. In this multicenter study, we combined quantitative deep urinary proteomics and machine learning to predict severe acute outcomes in hospitalized COVID-19 patients. Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrated predictive power for both discovery and validation set with 87% and 79% accuracy, respectively.

Integrins in biliary injury and fibrosis.

Purpose Of Review: Current treatment options for cholangiopathies are severely limited and there is thus a critical need to identify and develop therapies. This review discusses the role of integrins in biliary injury and fibrosis and their potential as therapeutic targets.

Recent Findings: There are a diverse set of roles that integrins play in biliary injury and fibrosis.

Spatial Heterogeneity of Glomerular Phenotypes Affects Kidney Biopsy Findings.

Key Points: Glomeruli with pathologic changes are not homogeneously distributed throughout the kidney cortex. Biopsies that do not include the kidney capsule may underdetect glomeruli with pathologic changes. Location of glomeruli with pathologic changes may be related to underlying clinical characteristics.

Cheminformatics Microservice: unifying access to open cheminformatics toolkits.

In recent years, cheminformatics has experienced significant advancements through the development of new open-source software tools based on various cheminformatics programming toolkits. However, adopting these toolkits presents challenges, including proper installation, setup, deployment, and compatibility management. In this work, we present the Cheminformatics Microservice.

Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental Glaucoma.

A major risk factor for glaucomatous optic neuropathy is the level of intraocular pressure (IOP), which can lead to retinal ganglion cell axon injury and cell death. The optic nerve has a rostral unmyelinated portion at the optic nerve head followed by a caudal myelinated region. The unmyelinated region is differentially susceptible to IOP-induced damage in rodent models and human glaucoma.

Genome-wide Association Study for AKI.

Key Points: Two genetic variants in the DISP1-TLR5 gene locus were associated with risk of AKI. DISP1 and TLR5 were differentially regulated in kidney biopsy tissue from patients with AKI compared with no AKI.

Background: Although common genetic risks for CKD are well established, genetic factors influencing risk for AKI in hospitalized patients are poorly understood.

Open data and algorithms for open science in AI-driven molecular informatics.

Recent years have seen a sharp increase in the development of deep learning and artificial intelligence-based molecular informatics. There has been a growing interest in applying deep learning to several subfields, including the digital transformation of synthetic chemistry, extraction of chemical information from the scientific literature, and AI in natural product-based drug discovery. The application of AI to molecular informatics is still constrained by the fact that most of the data used for training and testing deep learning models are not available as FAIR and open data.

SGLT2 inhibitors mitigate kidney tubular metabolic and mTORC1 perturbations in youth-onset type 2 diabetes.

The molecular mechanisms of sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) remain incompletely understood. Single-cell RNA sequencing and morphometric data were collected from research kidney biopsies donated by young persons with type 2 diabetes (T2D), aged 12 to 21 years, and healthy controls (HCs). Participants with T2D were obese and had higher estimated glomerular filtration rates and mesangial and glomerular volumes than HCs.

MORTAR: a rich client application for in silico molecule fragmentation.

Developing and implementing computational algorithms for the extraction of specific substructures from molecular graphs (in silico molecule fragmentation) is an iterative process. It involves repeated sequences of implementing a rule set, applying it to relevant structural data, checking the results, and adjusting the rules. This requires a computational workflow with data import, fragmentation algorithm integration, and result visualisation.

An algorithm to classify homologous series within compound datasets.

Homologous series are groups of related compounds that share the same core structure attached to a motif that repeats to different degrees. Compounds forming homologous series are of interest in multiple domains, including natural products, environmental chemistry, and drug design. However, many homologous compounds remain unannotated as such in compound datasets, which poses obstacles to understanding chemical diversity and their analytical identification via database matching.

Scaffold Generator: a Java library implementing molecular scaffold functionalities in the Chemistry Development Kit (CDK).

The concept of molecular scaffolds as defining core structures of organic molecules is utilised in many areas of chemistry and cheminformatics, e.g. drug design, chemical classification, or the analysis of high-throughput screening data.

Epifluorescent single-molecule counting with Streptavidin-Phycoerythrin conjugates.

Single-molecule methods, specifically single-molecule counting, convey high sensitivity in research applications. However, single-molecule counting experiments require specialized equipment or consumables to perform. We demonstrate the utility of using bright Streptavidin-Phycoerythrin (SA-PE) conjugates and an epifluorescence microscope, for single-molecule counting applications.

Affinity of anti-spike antibodies to three major SARS-CoV-2 variants in recipients of three major vaccines.

Background: Measuring anti-viral antibody affinity in blood plasma or serum is a rational quantitative approach to assess humoral immune response and acquired protection. Three common vaccines against SARS-CoV-2-Comirnaty developed by Pfizer/BioNTech, Spikevax developed by Moderna/NIAID, and Jcovden (previously Janssen COVID-19 Vaccine) developed by Johnson & Johnson/Janssen (J&J)-induce antibodies to a variety of immunogenic epitopes including the epitopes located in the ACE2 receptor-binding domain (RBD) of the spike protein. Blocking RBD with antibodies interferes with the binding of the virus to ACE2 thus protecting against infection.

Young Adult Anxiety or Depressive Symptoms and Mental Health Service Utilization During the COVID-19 Pandemic.

Purpose: Young adult anxiety/depression (mental health) symptoms have increased from prior to the COVID-19 pandemic. This study assessed young adult (aged 18-25 years) anxiety/depressive symptoms, mental health care utilization (prescription drug use, counseling, and/or either), and unmet counseling/therapy needs utilizing the national Household Pulse Survey data from June to July 2021.

Methods: Young adult (n = 2,809) rates and subgroup differences in mental health symptoms (Generalized Anxiety Disorder-2 and/or Patient Health Questionnaire-2) were assessed, as were mental health care utilization and unmet counseling/therapy needs.