Substitution of animal-based with plant-based foods on cardiometabolic health and all-cause mortality: a systematic review and meta-analysis of prospective studies.

Background: There is growing evidence that substituting animal-based with plant-based foods is associated with a lower risk of cardiovascular diseases (CVD), type 2 diabetes (T2D), and all-cause mortality. Our aim was to summarize and evaluate the evidence for the substitution of any animal-based foods with plant-based foods on cardiometabolic health and all-cause mortality in a systematic review and meta-analysis.

Methods: We systematically searched MEDLINE, Embase, and Web of Science to March 2023 for prospective studies investigating the substitution of animal-based with plant-based foods on CVD, T2D, and all-cause mortality.

An unconventional gatekeeper mutation sensitizes inositol hexakisphosphate kinases to an allosteric inhibitor.

Inositol hexakisphosphate kinases (IP6Ks) are emerging as relevant pharmacological targets because a multitude of disease-related phenotypes has been associated with their function. While the development of potent IP6K inhibitors is gaining momentum, a pharmacological tool to distinguish the mammalian isozymes is still lacking. Here, we implemented an analog-sensitive approach for IP6Ks and performed a high-throughput screen to identify suitable lead compounds.

Small Molecules Targeting Human UDP-GlcNAc 2-Epimerase.

Uridine diphosphate N-acetylglucosamine 2-epimerase (GNE) is a key enzyme in the sialic acid biosynthesis pathway. Sialic acids are primarily terminal carbohydrates on glycans and play fundamental roles in health and disease. In search of effective GNE inhibitors not based on a carbohydrate scaffold, we performed a high-throughput screening campaign of 68,640 drug-like small molecules against recombinant GNE using a UDP detection assay.

CLK2 and CLK4 are regulators of DNA damage-induced NF-κB targeted by novel small molecule inhibitors.

Transcription factor NF-κB potently activates anti-apoptotic genes, and its inactivation significantly reduces tumor cell survival following genotoxic stresses. We identified two structurally distinct lead compounds that selectively inhibit NF-κB activation by DNA double-strand breaks, but not by other stimuli, such as TNFα. Our compounds do not directly inhibit previously identified regulators of this pathway, most critically including IκB kinase (IKK), but inhibit signal transmission in-between ATM, PARP1, and IKKγ.

On the Functional Role of Gamma Synchronization in the Retinogeniculate System of the Cat.

Fast gamma oscillations, generated within the retina, and transmitted to the cortex via the lateral geniculate nucleus (LGN), are thought to carry information about stimulus size and continuity. This hypothesis relies mainly on studies conducted under anesthesia and the extent to which it holds under more naturalistic conditions remains unclear. Using multielectrode recordings of spiking activity in the retina and the LGN of both male and female cats, we show that visually driven gamma oscillations are absent for awake states and are highly dependent on halothane (or isoflurane).

The FGFR inhibitor PD173074 binds to the C-terminus of oncofetal HMGA2 and modulates its DNA-binding and transcriptional activation functions.

The architectural chromatin factor high-mobility group AT-hook 2 (HMGA2) is causally involved in several human malignancies and pathologies. HMGA2 is not expressed in most normal adult somatic cells, which renders the protein an attractive drug target. An established cell-based compound library screen identified the fibroblast growth factor receptor (FGFR) inhibitor PD173074 as an antagonist of HMGA2-mediated transcriptional reporter gene activation.

Risk phenotypes of diabetes and association with COVID-19 severity and death: an update of a living systematic review and meta-analysis.

Aims/hypothesis: To provide a systematic overview of the current body of evidence on high-risk phenotypes of diabetes associated with COVID-19 severity and death.

Methods: This is the first update of our recently published living systematic review and meta-analysis. Observational studies investigating phenotypes in individuals with diabetes and confirmed SARS-CoV-2 infection with regard to COVID-19-related death and severity were included.

Cortical maps as a fundamental neural substrate for visual representation.

Visual perception is the product of serial hierarchical processing, parallel processing, and remapping on a dynamic network involving several topographically organized cortical visual areas. Here, we will focus on the topographical organization of cortical areas and the different kinds of visual maps found in the primate brain. We will interpret our findings in light of a broader representational framework for perception.

Small molecule inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation.

Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia.

Dietary Factors and All-Cause Mortality in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Prospective Observational Studies.

Background: Type 2 diabetes is a major health concern associated with mortality. Diet may influence the progression of diabetes; however, systematic reviews are lacking.

Purpose: This study systematically summarized the evidence on diet and all-cause mortality in individuals with type 2 diabetes.

The Increased Clinical and Economic Burden of Hyperkalemia in Medicare Patients Admitted to Long-Term Care Settings.

Introduction: Older patients are at increased risk for hyperkalemia (HK). This study describes the prevalence, recurrence, and clinical and economic burden of HK in Medicare patients admitted to a long-term care (LTC) setting.

Methods: Retrospective cohort study using 100% Medicare Fee-for-Service (FFS) claims identified patients aged ≥ 65 years with index admission between 2017 and 2019 to a LTC setting (skilled nursing, home health, inpatient rehabilitation, or long-term acute care).

Physical Activity and Risk of Major Diabetes-Related Complications in Individuals With Diabetes: A Systematic Review and Meta-Analysis of Observational Studies.

Background: Physical activity is a cornerstone in diabetes management; however, evidence synthesis on the association between physical activity and long-term diabetes-related complications is scarce.

Purpose: To summarize and evaluate findings on physical activity and diabetes-related complications, we conducted a systematic review and meta-analysis.

Data Sources: We searched PubMed, Web of Science, and the Cochrane Library for articles published up to 6 July 2021.

Glycolytic flux control by drugging phosphoglycolate phosphatase.

Targeting the intrinsic metabolism of immune or tumor cells is a therapeutic strategy in autoimmunity, chronic inflammation or cancer. Metabolite repair enzymes may represent an alternative target class for selective metabolic inhibition, but pharmacological tools to test this concept are needed. Here, we demonstrate that phosphoglycolate phosphatase (PGP), a prototypical metabolite repair enzyme in glycolysis, is a pharmacologically actionable target.

Haplotype sequence collection of ABO blood group alleles by long-read sequencing reveals putative A1-diagnostic variants.

In the era of blood group genomics, reference collections of complete and fully resolved blood group gene alleles have gained high importance. For most blood groups, however, such collections are currently lacking, as resolving full-length gene sequences as haplotypes (ie, separated maternal/paternal origin) remains exceedingly difficult with both Sanger and short-read next-generation sequencing. Using the latest third-generation long-read sequencing, we generated a collection of fully resolved sequences for all 6 main ABO allele groups: ABO∗A1/A2/B/O.

Assessing minipig compact jawbone quality at the microscale.

Preclinical studies often require animal models for in vivo experiments. Particularly in dental research, pig species are extensively used due to their anatomical similarity to humans. However, there is a considerable knowledge gap on the multiscale morphological and mechanical properties of the miniature pigs' jawbones, which is crucial for implant studies and a direct comparison to human tissue.

Classical biological of key horticultural pests in Africa: successes, challenges, and opportunities.

Classical biological control (CBC) is considered a safer and more sustainable alternative for management of alien-invasive species. This review presents recent advances in CBC of key horticultural insect pests using parasitoids in Africa. Several CBC programs have been undertaken targeting different insect pests of both fruits and vegetables, largely yielding outstanding success.

Spontaneous variability in gamma dynamics described by a damped harmonic oscillator driven by noise.

Circuits of excitatory and inhibitory neurons generate gamma-rhythmic activity (30-80 Hz). Gamma-cycles show spontaneous variability in amplitude and duration. To investigate the mechanisms underlying this variability, we recorded local-field-potentials (LFPs) and spikes from awake macaque V1.

Benchmarking metagenomics classifiers on ancient viral DNA: a simulation study.

Owing to technological advances in ancient DNA, it is now possible to sequence viruses from the past to track down their origin and evolution. However, ancient DNA data is considerably more degraded and contaminated than modern data making the identification of ancient viral genomes particularly challenging. Several methods to characterise the modern microbiome (and, within this, the virome) have been developed; in particular, tools that assign sequenced reads to specific taxa in order to characterise the organisms present in a sample of interest.

A new robust multivariate mode estimator for eye-tracking calibration.

We propose in this work a new method for estimating the main mode of multivariate distributions, with application to eye-tracking calibration. When performing eye-tracking experiments with poorly cooperative subjects, such as infants or monkeys, the calibration data generally suffer from high contamination. Outliers are typically organized in clusters, corresponding to fixations in the time intervals when subjects were not looking at the calibration points.

Disruptors of AKAP-Dependent Protein-Protein Interactions.

A-kinase anchoring proteins (AKAPs) are a family of multivalent scaffolding proteins. They engage in direct protein-protein interactions with protein kinases, kinase substrates and further signaling molecules. Each AKAP interacts with a specific set of protein interaction partners and such sets can vary between different cellular compartments and cells.

Evaluation of whole-genome sequence data analysis approaches for short- and long-read sequencing of .

Whole-genome sequencing (WGS) of (MTB) isolates can be used to get an accurate diagnosis, to guide clinical decision making, to control tuberculosis (TB) and for outbreak investigations. We evaluated the performance of long-read (LR) and/or short-read (SR) sequencing for anti-TB drug-resistance prediction using the TBProfiler and Mykrobe tools, the fraction of genome recovery, assembly accuracies and the robustness of two typing approaches based on core-genome SNP (cgSNP) typing and core-genome multi-locus sequence typing (cgMLST). Most of the discrepancies between phenotypic drug-susceptibility testing (DST) and drug-resistance prediction were observed for the first-line drugs rifampicin, isoniazid, pyrazinamide and ethambutol, mainly with LR sequence data.

External Quality Assessment of SARS-CoV-2 Sequencing: an ESGMD-SSM Pilot Trial across 15 European Laboratories.

This first pilot trial on external quality assessment (EQA) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole-genome sequencing, initiated by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Genomic and Molecular Diagnostics (ESGMD) and the Swiss Society for Microbiology (SSM), aims to build a framework between laboratories in order to improve pathogen surveillance sequencing. Ten samples with various viral loads were sent out to 15 clinical laboratories that had free choice of sequencing methods and bioinformatic analyses. The key aspects on which the individual centers were compared were the identification of (i) single nucleotide polymorphisms (SNPs) and indels, (ii) Pango lineages, and (iii) clusters between samples.