Genome-wide interaction study with major depression identifies novel variants associated with cognitive function.

Major Depressive Disorder (MDD) often is associated with significant cognitive dysfunction. We conducted a meta-analysis of genome-wide interaction of MDD and cognitive function using data from four large European cohorts in a total of 3510 MDD cases and 6057 controls. In addition, we conducted analyses using polygenic risk scores (PRS) based on data from the Psychiatric Genomics Consortium (PGC) on the traits of MDD, Bipolar disorder (BD), Schizophrenia (SCZ), and mood instability (MIN).

TNF inhibition in vasculitis management in adenosine deaminase 2 deficiency (DADA2).

Background: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited autoinflammatory disorder caused by a loss of functional ADA2 protein. TNF inhibition (TNFi) has proven to be highly effective in treating inflammatory manifestations.

Objective: We sought to explore the pathophysiology and the underlying mechanisms of TNF-inhibitor response in these patients.

Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone.

Metabolic pathways regulate immune responses and disrupted metabolism leads to immune dysfunction and disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced immune responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non-COVID-19 patients, and 47 uninfected controls, we found an immunometabolic dysregulation in patients with progressed COVID-19.

GPR Expression in Intestinal Biopsies From SCT Patients Is Upregulated in GvHD and Is Suppressed by Broad-Spectrum Antibiotics.

Microbiota can exert immunomodulatory effects by short-chain fatty acids (SCFA) in experimental models of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT). Therefore we aimed to analyze the expression of SCFAs sensing G-protein coupled receptor GPR109A and GPR43 by quantitative PCR in 338 gastrointestinal (GI) biopsies obtained from 199 adult patients undergoing allo-SCT and assessed the interaction of GPR with FOXP3 expression and regulatory T cell infiltrates. GPR expression was strongly upregulated in patients with stage II-IV GvHD (p=0.

Epigenome-wide association study of alcohol use disorder in five brain regions.

Alcohol use disorder (AUD) is closely linked to the brain regions forming the neurocircuitry of addiction. Postmortem human brain tissue enables the direct study of the molecular pathomechanisms of AUD. This study aims to identify these mechanisms by examining differential DNA-methylation between cases with severe AUD (n = 53) and controls (n = 58) using a brain-region-specific approach, in which sample sizes ranged between 46 and 94.

Cancer Tissue Classification Using Supervised Machine Learning Applied to MALDI Mass Spectrometry Imaging.

Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) can determine the spatial distribution of analytes such as protein distributions in a tissue section according to their mass-to-charge ratio. Here, we explored the clinical potential of machine learning (ML) applied to MALDI MSI data for cancer diagnostic classification using tissue microarrays (TMAs) on 302 colorectal (CRC) and 257 endometrial cancer (EC)) patients. ML based on deep neural networks discriminated colorectal tumour from normal tissue with an overall accuracy of 98% in balanced cross-validation (98.

Prediction of corneal back surface power - Deep learning algorithm versus multivariate regression.

Background: The corneal back surface is known to add some against the rule astigmatism, with implications in cataract surgery with toric lens implantation. This study aimed to set up and validate a deep learning algorithm to predict corneal back surface power from the corneal front surface power and biometric measures.

Methods: This study was based on a large dataset of IOLMaster 700 measurements from two clinical centres.

Balloon catheter vs oxytocin alone for induction of labor in women with one previous cesarean section and an unfavorable cervix: a multicenter, retrospective study.

Purpose: To compare the rate of vaginal birth between double-balloon catheter and oxytocin alone for induction of labor in women with one previous cesarean section and an unfavorable cervix.

Materials And Methods: A retrospective and observational study was conducted from 2013 to 2017, at the Saint-Etienne University Hospital where women received induction with a double-balloon catheter for 12 h and at the Grenoble Alpes University Hospital where women received induction with a low-dose oxytocin infusion. Primary outcome was the rate of vaginal birth.

Electron cryo-tomography reveals the subcellular architecture of growing axons in human brain organoids.

During brain development, axons must extend over great distances in a relatively short amount of time. How the subcellular architecture of the growing axon sustains the requirements for such rapid build-up of cellular constituents has remained elusive. Human axons have been particularly poorly accessible to imaging at high resolution in a near-native context.

Roles for Selenoprotein I and Ethanolamine Phospholipid Synthesis in T Cell Activation.

The selenoprotein family includes 25 members, many of which are antioxidant or redox regulating enzymes. A unique member of this family is Selenoprotein I (SELENOI), which does not catalyze redox reactions, but instead is an ethanolamine phosphotransferase (Ept). In fact, the characteristic selenocysteine residue that defines selenoproteins lies far outside of the catalytic domain of SELENOI.

Fever and hypothermia represent two populations of sepsis patients and are associated with outside temperature.

Background: Fever and hypothermia have been observed in septic patients. Their influence on prognosis is subject to ongoing debates.

Methods: We did a secondary analysis of a large clinical dataset from a quality improvement trial.

Association between genetic variants of the cholinergic system and postoperative delirium and cognitive dysfunction in elderly patients.

Background: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are frequent and serious complications after surgery. We aim to investigate the association between genetic variants in cholinergic candidate genes according to the Kyoto encyclopedia of genes and genomes - pathway: cholinergic neurotransmission with the development of POD or POCD in elderly patients.

Methods: This analysis is part of the European BioCog project ( www.

Prediction of total corneal power from measured anterior corneal power on the IOLMaster 700 using a feedforward shallow neural network.

Background: The corneal back surface is known to add some astigmatism against-the-rule, which has to be considered in cataract surgery with toric lens implantation. The purpose of this study was to set up a deep learning algorithm which predicts the total corneal power from keratometry and biometric measures.

Methods: Based on a large data set of measurements with the IOLMaster 700 from two clinical centres, data from N = 21 108 eyes were included, each record containing valid data for keratometry K, total keratometry TK, axial length AL, central corneal thickness CCT, anterior chamber depth ACD, lens thickness LT and horizontal corneal diameter W2W from an individual eye.

Caco-2/HT29-MTX co-cultured cells as a model for studying physiological properties and toxin-induced effects on intestinal cells.

Infectious gastrointestinal diseases are frequently caused by toxins secreted by pathogens which may impair physiological functions of the intestines, for instance by cholera toxin or by heat-labile enterotoxin. To obtain a functional model of the human intestinal epithelium for studying toxin-induced disease mechanisms, differentiated enterocyte-like Caco-2 cells were co-cultured with goblet cell-like HT29-MTX cells. These co-cultures formed a functional epithelial barrier, as characterized by a high electrical resistance and the presence of physiological intestinal properties such as glucose transport and chloride secretion which could be demonstrated electrophysiologically and by measuring protein expression.

Selenoprotein K deficiency-induced apoptosis: A role for calpain and the ERS pathway.

Selenoprotein K (SELENOK), an endoplasmic reticulum (ER) resident protein, is regulated by dietary selenium and expressed at a relatively high level in neurons. SELENOK has been shown to participate in oxidation resistance, calcium (Ca) flux regulation, and the ER-associated degradation (ERAD) pathway in immune cells. However, its role in neurons has not been elucidated.

Blood copper and risk of cardiometabolic diseases: a Mendelian randomization study.

Observational evidence links higher blood levels of copper with higher risk of cardiovascular diseases. However, whether those associations reflect causal links or can be attributed to confounding is still not fully clear. We investigated causal effects of copper on the risk of cardiometabolic endpoints (stroke, coronary artery disease [CAD] and type 2 diabetes) and cardiometabolic risk factors in two-sample Mendelian randomization (MR) studies.

HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders.

Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region.

An adaptation strategy to urban heat: hospital rooms with radiant cooling accelerate patient recovery.

Background: Patients with respiratory diseases are vulnerable to the effects of heat. Therefore, it is important to develop adaptation strategies for heat exposure. One option is to optimise the indoor environment.

Lasting Effects: Seven Year Results of the Castrop Nomogram for Femtosecond Laser-Assisted Paired Corneal Arcuate Incisions.

Purpose: Long-term results of arcuate incisions are rarely reported. This is unfortunate as long-term stability of astigmatic correction is of great interest to surgeons performing astigmatic correction. This study investigates the 7 year stability of results after application of femtosecond laser-assisted arcuate incisions with the Castrop nomogram.

Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1.

Somatic mutations in UBA1 involving hematopoietic stem and myeloid cells have been reported in patients with the newly defined VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Here, we report clinical hematologic manifestations and unique bone marrow (BM) features in 16 patients with VEXAS. All patients were male and had a history of severe autoinflammatory and rheumatologic manifestations and a somatic UBA1 mutation (p.

Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine.

Gastrointestinal infectious diseases remain an important issue for human and animal health. Investigations on gastrointestinal infectious diseases are classically performed in laboratory animals leading to the problem that species-specific models are scarcely available, especially when it comes to farm animals. The 3R principles of Russel and Burch were achieved using intestinal organoids of porcine jejunum.

Simulation of Corneal imaging properties for near objects.

Purpose: Using raytracing simulation to study the effect of corneal imaging metrics for different aperture sizes as a function of object distances with different schematic model eyes.

Methods: This raytracing simulation determined the best focus (with the least root-mean-square (rms) ray scatter) and the best wavefront focus (with least rms wavefront error) for four schematic model eyes (Liou-Brennan (LBME), Atchison (ATCHME), Gullstrand (GULLME) and Navarro (NAVME)) with 4 aperture sizes (2-5 mm) and 30 object distances in a logscale from 10 cm to 10 m plus infinity. For each configuration, 10,000 rays were traced through the cornea, and the aperture stop was located at the lens front apex plane as described in the model eyes.