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In this work, we propose to use a state-of-the-art evolutionary algorithm to set the discretization thresholds for gene expression profiles, using feedback from a classifier in order to maximize the accuracy of the predictions based on the discretized gene expression levels, while at the same time minimizing the number of different profiles obtained, to ease the understanding of the expert. The methodology is applied to a dataset containing COVID-19 patients that developed either mild or severe symptoms. The results show that the evolutionary approach performs better than a traditional discretization based on statistical analysis, and that it does preserve the sense-making necessary for practitioners to trust the results.

Parkinson’s disease patients suffer from both motor and nonmotor impairments. There is currently no cure for Parkinson’s disease, and the most commonly used treatment, levodopa, only functions as a temporary relief of motor symptoms. Inhibition of the expression of the L‐tryptophan‐catabolizing enzyme tryptophan 2,3‐dioxygenase (TDO) has been shown to inhibit aging‐related α‐synuclein toxicity in Caenorhabditis elegans. To evaluate TDO inhibition as a potential therapeutic strategy for Parkinson’s disease, a brain‐penetrable, small molecule TDO inhibitor was developed, referred to as NTRC 3531‐0. This compound potently inhibits human and mouse TDO in biochemical and cell‐based assays and is selective over IDO1, an evolutionary unrelated enzyme that catalyzes the same reaction. In mice, NTRC 3531‐0 increased plasma and brain L‐tryptophan levels after oral administration, demonstrating inhibition of TDO activity in vivo. The effect on Parkinson’s disease symptoms was evaluated in a rotenone‐induced Parkinson’s disease mouse model. A structurally dissimilar TDO inhibitor, LM10, was evaluated in parallel. Both inhibitors had beneficial effects on rotenone‐induced motor and cognitive dysfunction as well as rotenone‐induced dopaminergic cell loss and neuroinflammation in the substantia nigra. Moreover, both inhibitors improved intestinal transit and enhanced colon length, which indicates a reduction of the rotenone‐induced intestinal dysfunction. Consistent with this, mice treated with TDO inhibitor showed decreased expression of rotenone‐induced glial fibrillary acidic protein, which is a marker of enteric glial cells, and decreased α‐synuclein accumulation in the enteric plexus. Our data support TDO inhibition as a potential therapeutic strategy to decrease motor, cognitive, and gastrointestinal symptoms in Parkinson’s disease., Using two selective small molecule inhibitors, the inhibition of tryptophan 2,3‐dioxygenase (TDO) was validated as a potential new therapeutic approach for Parkinson's disease. In a rotenone‐induced mouse model of Parkinson's disease, TDO inhibitor treatment induced positive effects on central nervous system function. Moreover, in contrast to standard therapy, the TDO inhibitors acted peripherally on the intestinal phenotype by reducing the rotenone‐induced intestinal inflammatory response.

This article provides an overview of the design and methodology of the “Corona lockdown: how fit are you?” (CLOFIT) study, including the questionnaires and scales that were included in the online survey. The aim of the CLOFIT study was to investigate the psychosocial and health consequences of the coronavirus disease 2019 (COVID-19) pandemic in the Netherlands. The survey was conducted among the Dutch population to collect data on immune fitness and the psychological and health consequences of the 2019 coronavirus disease (COVID-19) pandemic lockdown in the Netherlands. The CLOFIT dataset contains measures from N = 1910 participants and is broadly representative of the Dutch general population. The dataset represents both sexes, a range of ages including the elderly, different education levels, and ethnic backgrounds. The cohort also includes people with a diverse health status and range of medication use.

The composition and activity of the intestinal microbial community structures can be beneficially modulated by nutritional components such as non‐digestible oligosaccharides and omega‐3 poly‐unsaturated fatty acids (n‐3 PUFAs). These components affect immune function, brain development and behaviour. We investigated the additive effect of a dietary combination of scGOS:lcFOS and n‐3 PUFAs on caecal content microbial community structures and development of the immune system, brain and behaviour from day of birth to early adulthood in healthy mice. Male BALB/cByJ mice received a control or enriched diet with a combination of scGOS:lcFOS (9:1) and 6% tuna oil (n‐3 PUFAs) or individually scGOS:lcFOS (9:1) or 6% tuna oil (n‐3 PUFAs). Behaviour, caecal content microbiota composition, short‐chain fatty acid levels, brain monoamine levels, enterochromaffin cells and immune parameters in the mesenteric lymph nodes (MLN) and spleen were assessed. Caecal content microbial community structures displayed differences between the control and dietary groups, and between the dietary groups. Compared to control diet, the scGOS:lcFOS and combination diets increased caecal saccharolytic fermentation activity. The diets enhanced the number of enterochromaffin cells. The combination diet had no effects on the immune cells. Although the dietary effect on behaviour was limited, serotonin and serotonin metabolite levels in the amygdala were increased in the combination diet group. The combination and individual interventions affected caecal content microbial profiles, but had limited effects on behaviour and the immune system. No apparent additive effect was observed when scGOS:lcFOS and n‐3 PUFAs were combined. The results suggest that scGOS:lcFOS and n‐3 PUFAs together create a balance—the best of both in a healthy host.

International audience; Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders characterised by behavioural impairment and deficiencies in social interaction and communication. A recent study estimated that 1 in 89 children have developed some form of ASD in European countries. Moreover, there is no specific treatment and since ASD is not a single clinical entity, the identification of molecular biomarkers for diagnosis remains challenging. Besides behavioural deficiencies, individuals with ASD often develop comorbid medical conditions including intestinal problems, which may reflect aberrations in the bidirectional communication between the brain and the gut. The impact of faecal microbial composition in brain development and behavioural functions has been repeatedly linked to ASD, as well as changes in the metabolic profile of individuals affected by ASD. Since metabolism is one of the major drivers of microbiome–host interactions, this review aims to report emerging literature showing shifts in gut microbiota metabolic function in ASD. Additionally, we discuss how these changes may be involved in and/or perpetuate ASD pathology. These valuable insights can help us to better comprehend ASD pathogenesis and may provide relevant biomarkers for improving diagnosis and identifying new therapeutic targets.

Primer sets are short DNA sequences of 18-22 base pairs, that can be used to verify the presence of a virus, and designed to attach to a specific part of a viral DNA. Designing a primer set requires choosing a region of DNA, avoiding the possibility of hybridization to a similar sequence, as well as considering its GC content and Tm (melting temperature). Coronaviruses, such as SARS-CoV-2, have a considerably large genome (around 30 thousand nucleotides) when compared to other viruses. With the rapid rise and spread of SARS-CoV-2 variants, it has become a priority to breach our lack of specific primers available for diagnosis of this new variants. Here, we propose an evolutionary-based approach to primer design, able to rapidly deliver a high-quality primer set for a target sequence of the virus variant. Starting from viral sequences collected from open repositories, the proposed approach is proven able to uncover a specific primer set for the B.1.1.7 SARS-CoV-2 variant. Only recently identified, B.1.1.7 is already considered potentially dangerous, as it presents a considerably higher transmissibility when compared to other variants.

This study investigated immunological changes during an alcohol hangover, and the possible difference between hangover-resistant and hangover-sensitive drinkers in terms of immune reactivity. Using a semi-naturalistic design, N = 36 healthy social drinkers (18 to 30 years old) provided saliva samples on a control day (after drinking no alcohol) and on a post-alcohol day. Hangover severity was rated directly after saliva collection. Cytokine concentrations, interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α, and hangover severity were compared between both test days and between hangover-sensitive and -resistant drinkers. Data from N = 35 drinkers (17 hangover-sensitive and 18 hangover-resistant) were included in the statistical analyses. Relative to the control day, there were significant increases in saliva IL-6 and IL-10 concentrations on the post-alcohol day. No significant differences in cytokine concentrations were found between hangover-sensitive and hangover-resistant drinkers, nor did any change in cytokine concentration correlate significantly with hangover severity. In line with previous controlled studies assessing cytokines in blood, the current naturalistic study using saliva samples also demonstrated that the immune system responds to high-level alcohol intake. However, further research is warranted, as, in contrast to previous findings in blood samples, changes in saliva cytokine concentrations did not differ significantly between hangover-sensitive and hangover-resistant drinkers, nor did they correlate significantly with hangover severity.

In 2020, three articles were published on a protein that can activate the immune system by binding to macrophage-inducible C-type lectin receptor (Mincle). In the articles, the protein was referred to as ‘SAP130, a subunit of the histone deacetylase complex.’ However, the Mincle ligand the authors aimed to investigate is splicing factor 3b subunit 3 (SF3B3). This splicing factor is unrelated to SAP130 (Sin3A associated protein 130, a subunit of the histone deacetylase-dependent Sin3A corepressor complex). The conclusions in the three articles were formulated for SF3B3, while the researchers used qPCR primers and antibodies against SAP130. We retraced the origins of the ambiguity about the two proteins and found that Online Mendelian Inheritance in Man (OMIM) added a Nature publication on SF3B3 as a reference for Sin3A associated protein 130 in 2016. Subsequently, companies such as Abcam referred to OMIM and the Nature article in their products for both SF3B3 and SAP130. In turn, the mistake by OMIM followed in the persistent and confusing use of ‘SAP130′ (spliceosome-associated protein 130) as an alternative symbol for SF3B3. With this report, we aim to eliminate the persistent confusion and separate the literature regarding the two proteins.

Background: Chronic obstructive pulmonary disease (COPD) is often accompanied by psychiatric problems, such as depression and anxiety, affecting both treatment outcomes and mortality. Evidence for the number of COPD patients using medication for these disorders is sparse. In this study, chronic antidepressant (ATD) and anxiolytic (ANX) drug use – to identify depression and anxiety – among COPD patients was compared with subjects with or without other chronic diseases. Methods: The NControl database containing prescription data of 800 pharmacies including 7 million individuals in The Netherlands was used. Patients of age 55+ years who received frequent prescriptions – at least two/year in 5 out of 6 years – for COPD medication, dermatological drugs, disease-modifying antirheumatic drugs (DMARDs), statins and oral glucose-lowering medication were analyzed for concomitant chronic use of ATDs and ANXs between 1 January 2013 and 1 January 2019. All other subjects aged 55+ years were included as a control group (control group 1). This group was further stratified into a group of subjects that received frequent prescriptions of any kind (control group 2). Results: 15.2% of the patients that receive COPD treatment ( n = 96,319), 15.3% of subjects that are treated for dermatological problems ( n = 62,865), 13.2% of subjects that receive DMARDs ( n = 7900), 11.6% of statins users ( n = 422,376) and 11.4% of oral glucose-lowering medication users ( n = 165,975) are also chronically treated for depression or anxiety, compared with 2.6% (control group 1; n = 3,290,608) and 11.4% (control group 2; n = 757,947). In general, female and 75+ years aged subjects showed a higher risk for using ATDs and ANXs chronically. In the COPD and the dermatological patient group the risk was the highest compared with the other patient groups. Conclusions: The rates of chronic ATD and ANX use and the risk of having depression and/or anxiety are especially high in COPD patients, indicating that psychiatric problems are more common in COPD than in most other chronic diseases. In general, age and gender strongly influence the risk of chronically using ATDs and ANXs. The reviews of this paper are available via the supplemental material section.

With the advancement of high-throughput DNA/RNA sequencing and computational analysis techniques, commensal bacteria are now considered almost as important as pathological ones. Understanding the interaction between these bacterial microbiota, host and asthma is crucial to reveal their role in asthma pathophysiology. Several airway and/or gut microbiome studies have shown associations between certain bacterial taxa and asthma. However, challenges remain before gained knowledge from these studies can be implemented into clinical practice, such as inconsistency between studies in choosing sampling compartments and/or sequencing approaches, variability of results in asthma studies, and not taking into account medication intake and diet composition especially when investigating gut microbiome. Overcoming those challenges, will help to better understand the complex asthma disease process. The therapeutic potential of using pro- and pre-biotics to prevent or reduce risk of asthma exacerbations requires further investigation. This review will focus on methodological issues regarding setting up a microbiome study, recent developments in asthma bacterial microbiome studies, challenges and future therapeutic potential. This article is protected by copyright. All rights reserved.

Supplemental material, sj-pdf-1-tar-10.1177_1753466620961696 for Higher prescription of antidepressants and/or anxiolytics among chronic obstructive pulmonary disease patients by Charlotte E. Pelgrim, Jan Maurik van den Heuvel, Gert Folkerts, Johan Garssen, Anke H. Maitland-van der Zee and Aletta D. Kraneveld in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pdf-5-tar-10.1177_1753466620961696 for Higher prescription of antidepressants and/or anxiolytics among chronic obstructive pulmonary disease patients by Charlotte E. Pelgrim, Jan Maurik van den Heuvel, Gert Folkerts, Johan Garssen, Anke H. Maitland-van der Zee and Aletta D. Kraneveld in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pdf-2-tar-10.1177_1753466620961696 for Higher prescription of antidepressants and/or anxiolytics among chronic obstructive pulmonary disease patients by Charlotte E. Pelgrim, Jan Maurik van den Heuvel, Gert Folkerts, Johan Garssen, Anke H. Maitland-van der Zee and Aletta D. Kraneveld in Therapeutic Advances in Respiratory Disease

Childhood asthma is a complex multifactorial disease usually treated with inhaled corticosteroids (ICS) as controller medication. However, large variability in treatment response to, ICS is observed. A uniform, integrated systems pharmacology approach is needed to disentangle the complexity of the disease and identify phenotypes that are predictive of therapy response.This study aims: •To identify genetic and non-genetic biomarkers to characterize phenotypes of non-response to standard asthma therapy with ICS•To construct computational algorithms that effectively predict phenotype of ICS response by using a set of system-wide biomarkers and their interactions with environmental and clinical factors.Design: pan-european observational case-control study in Germany, Slovenia,Spain and the Netherlands. This is a unique approach to classify different phenotypes of asthmatic children that do not respond to standard therapy with ICS. In the future, the results of this study can lead to improved treatment strategies for pediatric asthma patients.