Factors associated with ABCDEF bundle implementation for critically ill patients: An international cross-sectional survey in 54 countries.

Objectives: This study investigated the implementation of the ABCDEF bundle and the factors associated with its implementation according to national income levels.

Methods: This study is cross-sectional research. We conducted a secondary analysis of an international 1-day point-prevalence study that investigated the implementation of the ABCDEF bundle in critically ill patients.

Short-chain fatty acid metabolites propionate and butyrate are unique epigenetic regulatory elements linking diet, metabolism and gene expression.

The short-chain fatty acids (SCFAs) propionate and butyrate have beneficial health effects, are produced in large amounts by microbial metabolism and have been identified as unique acyl lysine histone marks. To better understand the function of these modifications, we used chromatin immunoprecipitation followed by sequencing to map the genome-wide location of four short-chain acyl histone marks, H3K18pr, H3K18bu, H4K12pr and H4K12bu, in treated and untreated colorectal cancer (CRC) and normal cells as well as in mouse intestines in vivo. We correlate these marks with open chromatin regions and gene expression to access the function of the target regions.

Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma.

Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study.

Quantitative RNA pseudouridine maps reveal multilayered translation control through plant rRNA, tRNA and mRNA pseudouridylation.

Pseudouridine (Ψ) is the most abundant RNA modification, yet studies of Ψ have been hindered by a lack of robust methods to profile comprehensive Ψ maps. Here we utilize bisulfite-induced deletion sequencing to generate transcriptome-wide Ψ maps at single-base resolution across various plant species. Integrating ribosomal RNA, transfer RNA and messenger RNA Ψ stoichiometry with mRNA abundance and polysome profiling data, we uncover a multilayered regulation of translation efficiency through Ψ modifications.

Co-profiling of single-cell gene expression and chromatin landscapes in stickleback pituitary.

The pituitary gland is a key endocrine gland with various physiological functions including metabolism, growth, and reproduction. It comprises several distinct cell populations that release multiple polypeptide hormones. Although the major endocrine cell types are conserved across taxa, the regulatory mechanisms of gene expression and chromatin organization in specific cell types remain poorly understood.

The genetic demographic history of the last hunter-gatherer population of the Himalayas.

Nepal, largely covered by the Himalayan mountains, hosts indigenous populations with distinct linguistic, cultural, and genetic characteristics. Among these populations, the Raute, Nepal's last nomadic hunter-gatherers, offer a unique insight into the genetic and demographic history of Himalayan foragers. Despite strong cultural connections to other regional foragers, the genetic history of this population remains understudied.

Terrestrial insect defences in the face of metal toxicity.

Recently, there has been growing concern about the impacts of metal pollutants on insect populations, particularly as human societies increasingly rely on metal-based technologies. Unlike organic pollutants, metals - both essential and non-essential - are non-degradable and readily accumulate in insect tissues, sometimes reaching hazardous levels. While numerous studies address how insects cope with pesticide pollution, there is a notable scarcity of knowledge regarding their abilities to confront metal pollution.

Harnessing Nature's Palette: Exploring Photosynthetic Pigments for Sustainable Biotechnology.

Photosynthetic microorganisms such as cyanobacteria, microalgae, and anoxygenic phototrophic bacteria (APB) have emerged as sustainable and economic biotechnology platforms due to their ability to transform energy from light into chemicals through photosynthesis. The light is absorbed by photosynthetic pigment-protein antenna complexes which are composed of pigments such as bacteriochlorophylls (BChl) and carotenoids in APB, and chlorophylls (Chl), phycobiliproteins (PBP), and carotenoids in cyanobacteria and microalgae. These photosynthetic pigments are essential in the physiology of photosynthetic microorganisms and offer significant health benefits due to their potent antioxidant activity, with properties that include anticancer, antiaging, antiproliferative, anti-inflammatory, and neuroprotective effects.

Phylogenomic insights into the taxonomy, ecology, and mating systems of the lorchel family Discinaceae (Pezizales, Ascomycota).

Lorchels, also known as false morels (Gyromitra sensu lato), are iconic due to their brain-shaped mushrooms and production of gyromitrin, a deadly mycotoxin. Molecular phylogenetic studies have hitherto failed to resolve deep-branching relationships in the lorchel family, Discinaceae, hampering our ability to settle longstanding taxonomic debates and to reconstruct the evolution of toxin production. We generated 75 draft genomes from cultures and ascomata (some collected as early as 1960), conducted phylogenomic analyses using 1542 single-copy orthologs to infer the early evolutionary history of lorchels, and identified genomic signatures of trophic mode and mating-type loci to better understand lorchel ecology and reproductive biology.

Supplying LSD1 with FAD in pancreatic cancer: a matter of protein-protein interaction?

Lysine-specific demethylase 1 (LSD1) is a key regulator in cancer epigenetic, and its activity is reliant on flavin adenine dinucleotide (FAD) as a cofactor. In this study, we investigated the correlation between LSD1 and FAD synthase isoform 2 (FADS2) protein levels in pancreatic ductal adenocarcinoma (PDAC) cell lines. We first assessed LSD1 protein and mRNA levels in mutant p53-expressing PANC-1 and MiaPaCa2 cells and p53-null AsPc-1 cells, compared to human pancreatic ductal epithelial (HPDE) controls.

Design, synthesis, and biological evaluation of novel thiourea derivatives as small molecule inhibitors for prostate specific membrane antigen.

Prostate cancer (PCa) has emerged to be the second leading cause of cancer-related deaths in men. Molecular imaging of PCa using targeted radiopharmaceuticals specifically to PCa cells promises accurate staging of primary disease, detection of localized and metastasized tumours, and helps predict the progression of the disease. Glutamate urea heterodimers have been popularly used as high-affinity small molecules in the binding pockets of popular and well-characterized PCa biomarker, prostate specific membrane antigen (PSMA).

Detection of Echinococcus spp. and other taeniid species in lettuces and berries: Two international multicenter studies from the MEmE project.

Cystic and alveolar echinococcosis are severe zoonotic diseases characterized by long asymptomatic periods lasting months or years. Viable Echinococcus spp. eggs released into the environment through the feces of canids can infect humans through accidental ingestion via hand-to-mouth contact or consumption of contaminated food or water.

A phase I study of temsirolimus in combination with metformin in patients with advanced or recurrent endometrial cancer.

Introduction: Molecular alterations in the PI3K/AKT and Ras/Raf/MEK/ERK pathways are frequently observed in patients with endometrial cancers. However, mTOR inhibitors, such as temsirolimus, have modest clinical benefits. In addition to inducing metabolic changes in cells, metformin activates AMPK, which in turn inhibits the mTOR pathway.

Clinical, histopathological and parasitological follow-up of dogs naturally infected by Leishmania infantum before and after miltefosine treatment and associated therapies.

In Brazil, Visceral Leishmaniases is caused by Leishmania infantum, and domestic dogs are the main reservoirs in its urban transmission cycle. As an alternative to euthanizing dogs, miltefosine has been used to treat canine visceral leishmaniasis since 2016. In this study, we have assessed the efficacy of miltefosine for treating canine visceral leishmaniasis in a new endemic area through follow-up of naturally infected dogs was evaluated.

Structural basis for TIR domain-mediated innate immune signaling by Toll-like receptor adaptors TRIF and TRAM.

Innate immunity relies on Toll-like receptors (TLRs) to detect pathogen-associated molecular patterns. The TIR (Toll/interleukin-1 receptor) domain-containing TLR adaptors TRIF (TIR domain-containing adaptor-inducing interferon-β) and TRAM (TRIF-related adaptor molecule) are essential for MyD88-independent TLR signaling. However, the structural basis of TRIF and TRAM TIR domain-based signaling remains unclear.

CAGI6 ID panel challenge: assessment of phenotype and variant predictions in 415 children with neurodevelopmental disorders (NDDs).

The Genetics of Neurodevelopmental Disorders Lab in Padua provided a new intellectual disability (ID) Panel challenge for computational methods to predict patient phenotypes and their causal variants in the context of the Critical Assessment of the Genome Interpretation, 6th edition (CAGI6). Eight research teams submitted a total of 30 models to predict phenotypes based on the sequences of 74 genes (VCF format) in 415 pediatric patients affected by Neurodevelopmental Disorders (NDDs). NDDs are clinically and genetically heterogeneous conditions, with onset in infant age.

Quantitative imaging of loop extruders rebuilding interphase genome architecture after mitosis.

How cells establish the interphase genome organization after mitosis is incompletely understood. Using quantitative and super-resolution microscopy, we show that the transition from a Condensin to a Cohesin-based genome organization occurs dynamically over 2 h. While a significant fraction of Condensins remains chromatin-bound until early G1, Cohesin-STAG1 and its boundary factor CTCF are rapidly imported into daughter nuclei in telophase, immediately bind chromosomes as individual complexes, and are sufficient to build the first interphase TAD structures.

Biomarkers.

Background: Emerging evidence underscores the importance of neuroinflammation in the progression of Alzheimer's disease (AD) pathophysiology. Recent studies indicate the involvement of the inflammatory mechanisms both in amyloid- β (Aβ) and tau deposition in the brain. Nevertheless, due to the complexity of the immune responses and the intricate interplay between the peripheral and the central nervous systems, identifying biomarkers that reflect the brain´s inflammatory state in AD has been a challenge.

Biomarkers.

Background: Recently, the development of ultra-sensitive immunoassays has allowed for the detection, in blood, of proteins related to the pathophysiology of Alzheimer's disease (AD), with phosphorylated tau (p-tau) being the most promising. However, current methods are often limited by their ability to measure one analyte, lacking the potential for discovery and inclusion of additional biomarkers with supplemental value. In this pilot study, we explored proteomic changes using the novel NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) platform, focusing on patients with mild cognitive impairment (MCI).

Rational Modification of a Cross-Linker for Improved Flexible Protein Structure Modeling.

Chemical cross-linking/mass spectrometry (XL-MS) has emerged as a complementary tool for mapping interaction sites within protein networks as well as gaining moderate-resolution native structural insight with minimal interference. XL-MS technology mostly relies on chemoselective reactions (cross-linking) between protein residues and a linker. DSSO represents a versatile cross-linker for protein structure investigation and in-cell XL-MS.

Biomarkers.

Background: The APOE ε4 variant is the largest known genetic risk factor for late-onset sporadic Alzheimer's disease (AD). Recent blood biomarker models include APOE ε4 status with plasma p-tau217 for higher accuracy for AD pathology. Thus, protein assays that can accurately determine ε4 carriership simultaneously with plasma p-tau217 would be advantageous for clinical use.

Biomarkers.

Background: Blood-based biomarkers offer a non-invasive and cost-effective means for Alzheimer's disease (AD) detection. In this study, we performed a direct comparison of these novel biomarkers in a memory clinic population to facilitate their implementation into clinical practice.

Method: We included a total of 208 patients with cognitive complaints from the BIODEGMAR cohort at Hospital del Mar (Barcelona, Spain).

Developing Topics.

Background: The accumulation of hyperphosphorylated, aggregated tau in neurons is one of the hallmarks of Alzheimer's disease (AD). Recent work in structural biology has solved the structure of tau fibrils in several tauopathies and found that the structure of the tau fibrils varies between diseases, but fibril structure is conserved among patients within the same disease, suggesting fibril structure relates to its pathogenicity. Tau fibrils derived from AD brain (AD PHFs) seed AD-like pathology in wild-type mice, yet efforts to recapitulate this seeding with recombinant fibrils have failed.

Drug Development.

Background: The TREAT-AD centers aim to improve Alzheimer's Disease (AD) research by offering free, high-quality tools and technologies. Lyn is a tyrosine kinase that belongs to the Src family kinases. The expression of Lyn and its activity have been implicated in AD.