Prediagnostic Plasma Nutrimetabolomics and Prostate Cancer Risk: A Nested Case-Control Analysis Within the EPIC Study.

: Nutrimetabolomics may reveal novel insights into early metabolic alterations and the role of dietary exposures on prostate cancer (PCa) risk. We aimed to prospectively investigate the associations between plasma metabolite concentrations and PCa risk, including clinically relevant tumor subtypes. : We used a targeted and large-scale metabolomics approach to analyze plasma samples of 851 matched PCa case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

MultiOmicsIntegrator: a nextflow pipeline for integrated omics analyses.

Motivation: Analysis of gene and isoform expression levels is becoming critical for the detailed understanding of biochemical mechanisms. In addition, integrating RNA-seq data with other omics data types, such as proteomics and metabolomics, provides a strong approach for consolidating our understanding of biological processes across various organizational tiers, thus promoting the identification of potential therapeutic targets.

Results: We present our pipeline, called MultiOmicsIntegrator (MOI), an inclusive pipeline for comprehensive omics analyses.

Genetically predicted gut bacteria, circulating bacteria-associated metabolites and pancreatic ductal adenocarcinoma: a Mendelian randomisation study.

Pancreatic ductal adenocarcinoma (PDAC) has high mortality and rising incidence rates. Recent data indicate that the gut microbiome and associated metabolites may play a role in the development of PDAC. To complement and inform observational studies, we investigated associations of genetically predicted abundances of individual gut bacteria and genetically predicted circulating concentrations of microbiome-associated metabolites with PDAC using Mendelian randomisation (MR).

Kinetic Trajectories of Glucose Uptake in Single Cancer Cells Reveal a Drug-Induced Cell-State Change Within Hours of Drug Treatment.

The development of drug resistance is a nearly universal phenomenon in patients with glioblastoma multiforme (GBM) brain tumors. Upon treatment, GBM cancer cells may initially undergo a drug-induced cell-state change to a drug-tolerant, slow-cycling state. The kinetics of that process are not well understood, in part due to the heterogeneity of GBM tumors and tumor models, which can confound the interpretation of kinetic data.

Exploring Automated Contouring Across Institutional Boundaries: A Deep Learning Approach with Mouse Micro-CT Datasets.

Image-guided mouse irradiation is essential to understand interventions involving radiation prior to human studies. Our objective is to employ Swin UNEt Transformers (Swin UNETR) to segment native micro-CT and contrast-enhanced micro-CT scans and benchmark the results against 3D no-new-Net (nnU-Net). Swin UNETR reformulates mouse organ segmentation as a sequence-to-sequence prediction task, using a hierarchical Swin Transformer encoder to extract features at 5 resolution levels, and connects to a Fully Convolutional Neural Network (FCNN)-based decoder via skip connections.

Protein homeostasis imprinting across evolution.

Protein homeostasis (a.k.a.

IRE1 endoribonuclease signaling promotes myeloid cell infiltration in glioblastoma.

Background: Intrinsic or environmental stresses trigger the accumulation of improperly folded proteins in the endoplasmic reticulum (ER), leading to ER stress. To cope with this, cells have evolved an adaptive mechanism named the unfolded protein response (UPR) which is hijacked by tumor cells to develop malignant features. Glioblastoma (GB), the most aggressive and lethal primary brain tumor, relies on UPR to sustain growth.

Mapping novel QTL and fine mapping of previously identified QTL associated with glucose tolerance using the collaborative cross mice.

A chronic metabolic illness, type 2 diabetes (T2D) is a polygenic and multifactorial complicated disease. With an estimated 463 million persons aged 20 to 79 having diabetes, the number is expected to rise to 700 million by 2045, creating a significant worldwide health burden. Polygenic variants of diabetes are influenced by environmental variables.

Metabolomic Signatures of Exposure to Nitrate and Trihalomethanes in Drinking Water and Colorectal Cancer Risk in a Spanish Multicentric Study (MCC-Spain).

We investigated the metabolomic profile associated with exposure to trihalomethanes (THMs) and nitrate in drinking water and with colorectal cancer risk in 296 cases and 295 controls from the Multi Case-Control Spain project. Untargeted metabolomic analysis was conducted in blood samples using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. A variety of univariate and multivariate association analyses were conducted after data quality control, normalization, and imputation.

Design and Synthesis of Novel 2-Acetamido, 6-Carboxamide Substituted Benzothiazoles as Potential BRAFV600E Inhibitors - In vitro Evaluation of their Antiproliferative Activity.

The oncogenic BRAFV600E kinase leads to abnormal activation of the MAPK signaling pathway and thus, uncontrolled cellular proliferation and cancer development. Based on our previous virtual screening studies which issued 2-acetamido-1,3 benzothiazole-6-carboxamide scaffold as active pharmacophore displaying selectivity against the mutated BRAF, eleven new substituted benzothiazole derivatives were designed and synthesized by coupling of 2-acetamidobenzo[d]thiazole-6-carboxylic acid with the appropriate amines in an effort to provide even more efficient inhibitors and tackle drug resistance often developed during cancer treatment. All derived compounds bore the benzothiazole scaffold substituted at position-2 by an acetamido moiety and at position-6 by a carboxamide functionality, the NH moiety of which was further linked through an alkylene linker to a sulfonamido (or amino) aryl (or alkyl) functionality or a phenylene linker to a sulfonamido aromatic (or non-aromatic) terminal pharmacophore in the order -C H -NHSO -R or reversely -C H -SO N(H)-R.

Moyamoya Disease: Clinical and Radiological Characteristics in Adult Greek Patients.

Background And Purpose: The aim of our study is to present, for the first time, the clinical, radiological, and neurocognitive characteristics of Greek adult patients with Moyamoya disease (MMD).

Methods: We analyzed prospectively collected data of 12 patients referred to our department from 2004 to 2019. All patients underwent a thorough diagnostic work up, including extensive clinical, neuroradiological, and neurocognitive assessment.

Biological Relevance of Goat Milk Oligosaccharides to Infant Health.

Milk is often regarded as the gold standard for the nourishment of all mammalian offspring. The World Health Organization (WHO) recommends exclusive breastfeeding for the first 6 months of the life of the infant, followed by a slow introduction of complementary foods to the breastfeeding routine for a period of approximately 2 years, whenever this is possible ( ; WHO, 2003). One of the most abundant components in all mammals' milk, which is associated with important health benefits, is the oligosaccharides.

Metabolic network construction reveals probiotic-specific alterations in the metabolic activity of a synthetic small intestinal community.

The development of probiotic therapies targeted at the small intestinal microbiota represents a significant advancement in the field of probiotic interventions. This region poses unique opportunities due to its low number of gut microbiota, along with the presence of heightened immune and metabolic host responses. However, progress in this area has been hindered by a lack of detailed understanding regarding the molecular mechanisms through which probiotics exert their effects in the small intestine.

Altered plasma metabolite levels can be detected years before a glioma diagnosis.

Genetic and metabolic changes in tissue and blood are reported to occur several years before glioma diagnosis. Since gliomas are currently detected late, a liquid biopsy for early detection could affect the quality of life and prognosis of patients. Here, we present a nested case-control study of 550 prediagnostic glioma cases and 550 healthy controls from the Northern Sweden Health and Disease study (NSHDS) and the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Detecting Skin Reactions in Epicutaneous Patch Testing with Deep Learning: An Evaluation of Pre-Processing and Modality Performance.

Epicutaneous patch testing is a well-established diagnostic method for identifying substances that may cause Allergic Contact Dermatitis (ACD), a common skin condition caused by exposure to environmental allergens. While the patch test remains the gold standard for identifying allergens, it is prone to observer bias and consumes valuable human resources. Deep learning models can be employed to address this challenge.

Dynamic effects of probiotic formula ecologic®825 on human small intestinal ileostoma microbiota: a network theory approach.

The gut microbiota plays a pivotal role in health and disease. The use of probiotics as microbiota-targeted therapies is a promising strategy to improve host health. However, the molecular mechanisms involved in such therapies are often not well understood, particularly when targeting the small intestinal microbiota.

A novel IRE1 kinase inhibitor for adjuvant glioblastoma treatment.

Inositol-requiring enzyme 1 (IRE1) is a major mediator of the unfolded protein response (UPR), which is activated upon endoplasmic reticulum (ER) stress. Tumor cells experience ER stress due to adverse microenvironmental cues, a stress overcome by relying on IRE1 signaling as an adaptive mechanism. Herein, we report the discovery of structurally new IRE1 inhibitors identified through the structural exploration of its kinase domain.

A CNN-based four-layer DOI encoding detector using LYSO and BGO scintillators for small animal PET imaging.

. We propose a novel four-layer depth-of-interaction (DOI) encoding phoswich detector using lutetium-yttrium oxyothosilicate (LYSO) and bismuth germanate (BGO) scintillator crystal arrays for high sensitivity and high spatial resolution small animal PET imaging..

Genomic characteristics and clinical significance of CD56+ circulating tumor cells in small cell lung cancer.

Circulating tumor cells (CTC) have been studied in various solid tumors but clinical utility of CTC in small cell lung cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics. CTC-CPC is a monocentric prospective non-interventional study including treatment-naïve newly diagnosed SCLC.