Simple quantitation and spatial characterization of label free cellular images.

Label-free imaging is routinely used during cell culture because of its minimal interference with intracellular biology and capability of observing cells over time. However, label-free image analysis is challenging due to the low contrast between foreground signals and background. So far various deep learning tools have been developed for label-free image analysis and their performance depends on the quality of training data.

Brain glycogen build-up measured by magnetic resonance spectroscopy in classic infantile Pompe disease.

Classic infantile Pompe disease is caused by abnormal lysosomal glycogen accumulation in multiple tissues, including the brain due to a deficit in acid α-glucosidase. Although treatment with recombinant human acid α-glucosidase has dramatically improved survival, recombinant human acid α-glucosidase does not reach the brain, and surviving classic infantile Pompe patients develop progressive cognitive deficits and white matter lesions. We investigated the feasibility of measuring non-invasively glycogen build-up and other metabolic alterations in the brain of classic infantile Pompe patients.

Functional and molecular profiling of fasted piglets reveals decreased energy metabolic function and cell proliferation in the small intestine.

The small intestine requires energy to exert its important role in nutrient uptake and barrier function. Pigs are an important source of food and a model for humans. Young piglets and infants can suffer from periods of insufficient food intake.

X-linked creatine transporter (SLC6A8) deficiency in females: Difficult to recognize, but a potentially treatable disease.

Creatine transporter deficiency (CTD), caused by pathogenic variants in SLC6A8, is the second most common cause of X-linked intellectual disability. Symptoms include intellectual disability, epilepsy, and behavioral disorders and are caused by reduced cerebral creatine levels. Targeted treatment with oral supplementation is available, however the treatment efficacy is still being investigated.

Hepatic Fibrosis Evaluated in Patients with Type 2 Diabetes with and without Chronic Kidney Disease.

Background: Non-alcoholic fatty liver disease (NAFLD), and particularly liver fibrosis, has been suggested as a risk factor of chronic kidney disease (CKD). Given that NAFLD affects every fourth person globally, better insight is needed. Our aim was to investigate the association between hepatic fibrosis and CKD in patients with type 2 diabetes and to compare different methods for diagnosing liver fibrosis in this study population.

Single and Joined Behaviour of Circulating Biomarkers and Metabolic Parameters in High-Fit and Low-Fit Healthy Females.

Biomarkers are important in the assessment of health and disease, but are poorly studied in still healthy individuals with a (potential) different risk for metabolic disease. This study investigated, first, how single biomarkers and metabolic parameters, functional biomarker and metabolic parameter categories, and total biomarker and metabolic parameter profiles behave in young healthy female adults of different aerobic fitness and, second, how these biomarkers and metabolic parameters are affected by recent exercise in these healthy individuals. A total of 102 biomarkers and metabolic parameters were analysed in serum or plasma samples from 30 young, healthy, female adults divided into a high-fit (V̇O2peak ≥ 47 mL/kg/min, N = 15) and a low-fit (V̇O2peak ≤ 37 mL/kg/min, N = 15) group, at baseline and overnight after a single bout of exercise (60 min, 70% V̇O2peak).

Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes and Chronic Kidney Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is suggested as a risk factor for chronic kidney disease (CKD). The incidence of NAFLD is rising globally in parallel to the increasing incidences of obesity and type 2 diabetes. Diabetes remains the leading cause of CKD, but the co-existence of NAFLD, CKD, and type 2 diabetes is not well elucidated.

FOXO3A-short is a novel regulator of non-oxidative glucose metabolism associated with human longevity.

Intronic single-nucleotide polymorphisms (SNPs) in FOXO3A are associated with human longevity. Currently, it is unclear how these SNPs alter FOXO3A functionality and human physiology, thereby influencing lifespan. Here, we identify a primate-specific FOXO3A transcriptional isoform, FOXO3A-Short (FOXO3A-S), encoding a major longevity-associated SNP, rs9400239 (C or T), within its 5' untranslated region.

Mastering the game of Stratego with model-free multiagent reinforcement learning.

We introduce DeepNash, an autonomous agent that plays the imperfect information game Stratego at a human expert level. Stratego is one of the few iconic board games that artificial intelligence (AI) has not yet mastered. It is a game characterized by a twin challenge: It requires long-term strategic thinking as in chess, but it also requires dealing with imperfect information as in poker.

Improved detection limits of J-coupled neurometabolites in the human brain at 7 T with a J-refocused sLASER sequence.

In a standard spin echo, the time evolution due to homonuclear couplings is not reversed, leading to echo time (TE)-dependent modulation of the signal amplitude and signal loss in the case of overlapping multiplet resonances. This has an adverse effect on quantification of several important metabolites such as glutamate and glutamine. Here, we propose a J-refocused variant of the sLASER sequence (J-sLASER) to improve quantification of J-coupled metabolites at ultrahigh field (UHF).

Add-On MEmaNtine to Dopamine Antagonism to Improve Negative Symptoms at First Psychosis- the AMEND Trial Protocol.

Background: Antipsychotic drugs are primarily efficacious in treating positive symptoms by blocking the dopamine D2 receptor, but they fail to substantially improve negative symptoms and cognitive deficits. The limited efficacy may be attributed to the fact that the pathophysiology of psychosis involves multiple neurotransmitter systems. In patients with chronic schizophrenia, memantine, a non-competitive glutamatergic NMDA receptor antagonist, shows promise for ameliorating negative symptoms and improving cognition.

Proton metabolic mapping of the brain at 7 T using a two-dimensional free induction decay-echo-planar spectroscopic imaging readout with lipid suppression.

The increased signal-to-noise ratio (SNR) and chemical shift dispersion at high magnetic fields (≥7 T) have enabled neuro-metabolic imaging at high spatial resolutions. To avoid very long acquisition times with conventional magnetic resonance spectroscopic imaging (MRSI) phase-encoding schemes, solutions such as pulse-acquire or free induction decay (FID) sequences with short repetition time and inner volume selection methods with acceleration (echo-planar spectroscopic imaging [EPSI]), have been proposed. With the inner volume selection methods, limited spatial coverage of the brain and long echo times may still impede clinical implementation.

Accuracy investigations for volumetric head-motion navigators with and without EPI at 7 T.

Purpose: Accuracy investigation of volumetric navigators for motion correction, with emphasis on geometric EPI distortions at ultrahigh field.

Methods: High-resolution Dixon images were collected in different head positions and reconstructed to water, fat, T *, and B maps. Resolution reduction was performed, and the T * and B maps were used to apply effects of TE and EPI distortions to simulate various volumetric water and fat navigators.

Identifying the source of spurious signals caused by B inhomogeneities in single-voxel H MRS.

Purpose: Single-voxel MRS (SV MRS) requires robust volume localization as well as optimized crusher and phase-cycling schemes to reduce artifacts arising from signal outside the volume of interest. However, due to local magnetic field gradients (B inhomogeneities), signal that was dephased by the crusher gradients during acquisition might rephase, leading to artifacts in the spectrum. Here, we analyzed this mechanism, aiming to identify the source of signals arising from unwanted coherence pathways (spurious signals) in SV MRS from a B map.

Locus Coeruleus Shows a Spatial Pattern of Structural Disintegration in Parkinson's Disease.

Background: Parkinson's disease (PD) causes a loss of neuromelanin-positive, noradrenergic neurons in the locus coeruleus (LC), which has been implicated in nonmotor dysfunction.

Objectives: We used "neuromelanin sensitive" magnetic resonance imaging (MRI) to localize structural disintegration in the LC and its association with nonmotor dysfunction in PD.

Methods: A total of 42 patients with PD and 24 age-matched healthy volunteers underwent magnetization transfer weighted (MTw) MRI of the LC.

Extracellular flux analyses reveal differences in mitochondrial PBMC metabolism between high-fit and low-fit females.

Analyzing metabolism of peripheral blood mononuclear cells (PBMCs) can possibly serve as a cellular metabolic read-out for lifestyle factors and lifestyle interventions. However, the impact of PBMC composition on PBMC metabolism is not yet clear, neither is the differential impact of a longer-term lifestyle factor versus a short-term lifestyle intervention. We investigated the effect of aerobic fitness level and a recent exercise bout on PBMC metabolism in females.

The Effect of a Single Bout of Exercise on Vitamin B2 Status Is Not Different between High- and Low-Fit Females.

High-fitness individuals have been suggested to be at risk of a poor vitamin B2 (riboflavin) status due to a potentially higher vitamin B2 demand, as measured by the erythrocyte glutathione reductase (EGR) activation coefficient (EGRAC). Longer-term exercise interventions have been shown to result in a lower vitamin B2 status, but studies are contradictory. Short-term exercise effects potentially contribute to discrepancies between studies but have only been tested in limited study populations.

Butyrate Alters Pyruvate Flux and Induces Lipid Accumulation in Cultured Colonocytes.

Butyrate is considered the primary energy source of colonocytes and has received wide attention due to its unique health benefits. Insight into the mechanistic effects of butyrate on cellular and metabolic function relies mainly on research in in-vitro-cultured cells. However, cells in culture differ from those in terms of metabolic phenotype and nutrient availability.

The female mouse is resistant to mild vitamin B deficiency.

Purpose: Vitamin B provides nicotinamide adenine dinucleotide (NAD), an essential coenzyme in oxidoreductase reactions. Severe vitamin B deficiency leads to the disease Pellagra, while mild vitamin B deficiency has been linked to age-related and metabolic diseases. Mild vitamin B deficiency is understudied, especially in females.

OCRbayes: A Bayesian hierarchical modeling framework for Seahorse extracellular flux oxygen consumption rate data analysis.

Background: Mitochondrial dysfunction is involved in many complex diseases. Efficient and accurate evaluation of mitochondrial functionality is crucial for understanding pathology as well as facilitating novel therapeutic developments. As a popular platform, Seahorse extracellular flux (XF) analyzer is widely used for measuring mitochondrial oxygen consumption rate (OCR) in living cells.

Matrisome, innervation and oxidative metabolism affected in older compared with younger males with similar physical activity.

Background: Due to the interaction between skeletal muscle ageing and lifestyle factors, it is often challenging to attribute the decline in muscle mass and quality to either changes in lifestyle or to advancing age itself. Because many of the physiological factors affecting muscle mass and quality are modulated by physical activity and physical activity declines with age, the aim of this study is to better understand the effects of early ageing on muscle function by comparing a population of healthy older and young males with similar physical activity patterns.

Methods: Eighteen older (69 ± 2.