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Purpose: The purpose of this paper is to analyse data literacy in the new Digital Competence Framework for Citizens (DigComp 2.2). Mid-2022 the Joint Research Centre of the European Commission published a new version of the DigComp (EC, 2022). This new version focusses more on the datafication of society and emerging technologies, such as artificial intelligence. This paper analyses how DigComp 2.2 defines data literacy and how the framework looks at this from a societal lens. Design/methodology/approach: This study critically examines DigComp 2.2, using the data literacy competence model developed by the Knowledge Centre for Digital and Media Literacy Flanders-Belgium. The examples of knowledge, skills and attitudes focussing on data literacy (n = 84) are coded and mapped onto the data literacy competence model, which differentiates between using data and understanding data. Findings: Data literacy is well-covered in the framework, but there is a stronger emphasis on understanding data rather than using data, for example, collecting data is only coded once. Thematically, DigComp 2.2 primarily focusses on security and privacy (31 codes), with less attention given to the societal impact of data, such as environmental impact or data fairness. Originality/value: Given the datafication of society, data literacy has become increasingly important. DigComp is widely used across different disciplines and now integrates data literacy as a required competence for citizens. It is, thus, relevant to analyse its views on data literacy and emerging technologies, as it will have a strong impact on education in Europe.

Abstract Lipopolysaccharide (LPS) is one of the most potent mediators of inflammation. In swine husbandry, weaning is associated with LPS-induced intestinal inflammation, resulting in decreased growth rates due to malabsorption of nutrients by the inflamed gut. A potential strategy to treat LPS-mediated disease is administering intestinal alkaline phosphatase (IAP). The latter can detoxify lipid A, the toxic component of LPS, by removal of phosphate groups. Currently, 183 LPS O-serotypes from E. coli have been described, however, comparative experiments to elucidate functional differences between LPS serotypes are scarce. In addition, these functional differences might affect the efficacy of LPS detoxifying enzymes. Here, we evaluated the ability of four LPS serotypes (O26:B6, O55:B5, O111:B4 and O127:B8) derived from Escherichia coli to trigger the secretion of pro-inflammatory cytokines by porcine PBMCs. We also tested the ability of three commercially available IAPs to detoxify these LPS serotypes. The results show that LPS serotypes differ in their ability to trigger cytokine secretion by immune cells, especially at lower concentrations. Moreover, IAPs displayed a different detoxification efficiency of the tested serotypes. Together, this study sheds light on the impact of LPS structure on the detoxification by IAPs. Further research is however needed to elucidate the LPS serotype-specific effects and their implications for the development of novel treatment options to alleviate LPS-induced gut inflammation in weaned piglets.

Abstract Dengue virus (DENV) is the most prevalent arthropod-borne flavivirus and imposes a significant healthcare threat worldwide. At present no FDA-approved specific antiviral treatment is available, and the safety of a vaccine against DENV is still on debate. Following its entry into the host cell, DENV takes advantage of the cellular secretory pathway to produce new infectious particles. The key organelle of the host cell in DENV infections is the endoplasmic reticulum (ER) which supports various stages throughout the entire life cycle of flaviviruses. This review delves into the intricate interplay between flaviviruses and the ER during their life cycle with a focus on the molecular mechanisms underlying viral replication, protein processing and virion assembly. Emphasizing the significance of the ER in the flavivirus life cycle, we highlight potential antiviral targets in ER-related steps during DENV replication and summarize the current antiviral drugs that are in (pre)clinical developmental stage. Insights into the exploitation of the ER by DENV offer promising avenues for the development of targeted antiviral strategies, providing a foundation for future research and therapeutic interventions against flaviviruses.

Summary: Neuroinflammation and dysregulated energy metabolism are linked to motor neuron degeneration in amyotrophic lateral sclerosis (ALS). The egl-9 family hypoxia-inducible factor (EGLN) enzymes, also known as prolyl hydroxylase domain (PHD) enzymes, are metabolic sensors regulating cellular inflammation and metabolism. Using an oligonucleotide-based and a genetic approach, we showed that the downregulation of Egln2 protected motor neurons and mitigated the ALS phenotype in two zebrafish models and a mouse model of ALS. Single-nucleus RNA sequencing of the murine spinal cord revealed that the loss of EGLN2 induced an astrocyte-specific downregulation of interferon-stimulated genes, mediated via the stimulator of interferon genes (STING) protein. In addition, we found that the genetic deletion of EGLN2 restored this interferon response in patient induced pluripotent stem cell (iPSC)-derived astrocytes, confirming the link between EGLN2 and astrocytic interferon signaling. In conclusion, we identified EGLN2 as a motor neuron protective target normalizing the astrocytic interferon-dependent inflammatory axis in vivo, as well as in patient-derived cells.

BackgroundAs the therapeutic landscape for inflammatory bowel disease (IBD) continues to expand, a need exists to understand how patients perceive and value different attributes associated with their disease as well as with current and emerging treatments. These insights can inform the development and regulation of effective interventions for IBD, benefiting various stakeholders including healthcare professionals, drug developers, regulators, Health Technology Assessment bodies, payers, and ultimately patients suffering from IBD. In response to this, the present patient preference study was developed with the aim to (1) determine the relative preference weights for IBD treatment and disease related attributes, and (2) explain how preferences may differ across patients with different characteristics (preference heterogeneity).MethodsThe patient preference study (PPS) was developed through an 8-step process, with each step being informed by an advisory board. This process included: (1) stated preference method selection, (2) attribute and level development (including a scoping literature review, focus group discussions, and advisory board meetings), (3) choice task construction, (4) sample size estimation, (5) survey implementation, (6) piloting, (7) translation, and (8) pre-testing. The resulting discrete choice experiment (DCE) survey comprises 14 attributes with between two and five varying levels. Participants will answer 15 DCE questions with a partial profile design, where each of the choice questions encompasses two hypothetical treatment profiles showing four attributes. Additionally, questions about patients' socio-demographic and clinical characteristics, as well as contextual factors are implemented. The survey is available in 15 different languages and aims to minimally recruit 700 patients globally.DiscussionThis protocol gives valuable insights toward preference researchers and decision-makers on how PPS design can be transparently reported, demonstrating solutions to remaining gaps in preference research. Results of the PPS will provide evidence regarding the disease and treatment related characteristics that are most important for IBD patients, and how these may differ across patients with different characteristics. These findings will yield valuable insights applicable to preference research, drug development, regulatory approval, and reimbursement processes, enabling decision making across the medicinal product life cycle that is aligned with the true needs of IBD patients.

The effects of fire seasonality and prescribed burning on exotic species invasion are poorly understood in black greasewood (Sarcobatus vermiculatus) plant communities of North America. The impacts of reintroducing fire in the fall and spring on community composition and current-year biomass were evaluated at two such sites, one dominated by exotic annual C3 grasses in Miles City, Montana, USA, and one dominated by native perennial C4 grasses in Laramie, Wyoming, USA. Study sites were assessed based on existing Ecological Site Description (ESD) and State-and-Transition Models (STMs) and the Montana site was determined to be more degraded than the Wyoming site. Experimental design was a randomized complete block design with burns conducted in the fall of 2020 and spring of 2021. Exotic species such as Bromus arvensis were reduced by 56% in spring burned plots the following year and by 25% in the fall burned plots over the course of the study in Montana (58.3–43.5%) and Bromus tectorum did not increase in spring or fall burned plots in Wyoming. Accordingly, the proportion of native species in both plant communities remained constant and native perennial C4 grasses such as Sporobolus airoides were resilient to fire. Moreover, burn treatment had no negative effects on plant species richness, evenness, or diversity in either location. Fire treatments had variable effects on current-year biomass with variable influences of drought and season of burn. Prescribed fire, regardless of season, did not exacerbate exotic plant species spread or reduce native species dominance in either location – suggesting that phreatophytic S. vermiculatus rangelands near the eastern terminus of their range are resilient to anthropogenic burning. Future research should investigate the use of prescribed fire with other methods such as revegetation and herbicide application for reducing exotic plant dominance and increasing native plant species.

Introduction Symptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk of complications, compared with the achievement of endoscopic remission alone. The actiVE ulcerative colitis, a RanDomIsed Controlled Trial (VERDICT) aims to determine the optimal treatment target in patients with UC.Methods and analysis In this multicentre, prospective randomised study, 660 patients with moderate to severe UC (Mayo rectal bleeding subscore [RBS] ≥1; Mayo endoscopic score [MES] ≥2) are randomly assigned to three treatment targets: corticosteroid-free symptomatic remission (Mayo RBS=0) (group 1); corticosteroid-free endoscopic remission (MES ≤1) and symptomatic remission (group 2); or corticosteroid-free histologic remission (Geboes score

Abstract Introduction Chronic inflammatory diseases, including psoriasis, are associated with development of venous thromboembolism (VTE). The clot lysis profile (CLP) provides information on both the clotting tendency and fibrinolysis activity. We hypothesized that CLP in uncontrolled psoriasis patients is disturbed towards more clotting/less lysis compared to healthy controls (HC) and that successful psoriasis treatment could normalize the CLP. In this project, we aim to compare the CLP in patients with uncontrolled psoriasis with age- and sex-matched HC and investigate the effect of anti-inflammatory treatment on CLP. Methods Patients with uncontrolled psoriasis [psoriasis area severity index (PASI) or body surface area (BSA) > 10] (n = 87) and HC (n = 87) were recruited at a tertiary dermatology department. Samples from patients were obtained before treatment and when disease control was obtained (PASI

Acetate-producing Saccharomyces cerevisiae var. boulardii strains could exert improved effects on ulcerative colitis, which here, was preclinically evaluated in an acute dextran sodium sulphate induced model of colitis. Nine-week-old female mice were divided into 12 groups, receiving either drinking water or 2.75% dextran sodium sulphate for 7 days, combined with a daily gavage of various treatments with different levels of acetate accumulation: sham control (phosphate buffered saline, no acetate), non-probiotic control (Baker’s yeast, no acetate), probiotic control (Enterol®, transient acetate), and additionally several Saccharomyces cerevisiae var. boulardii strains with respectively no, high, and extra-high acetate accumulation. Disease activity was monitored daily, and feces samples were collected at different timepoints. On day 14, the mice were sacrificed, upon which blood and colonic tissue were collected for analysis. Disease activity in inflamed mice was lower when treated with the high-acetate-producing strain compared to sham and non-probiotic controls. The non-acetate-producing strain showed higher disease activity compared to the acetate-producing strains. Accordingly, higher histologic inflammation was observed in non- or transient-acetate-producing strains compared to the sham control, whereas this increase was not observed for high- and extra-high-acetate-producing strains upon induction of inflammation. These anti-inflammatory findings were confirmed by transcriptomic analysis of differentially expressed genes. Moreover, only the strain with the highest acetate production was superior in maintaining a stable gut microbial alpha-diversity upon inflammation. These findings support new possibilities for acetate-mediated management of inflammation in inflammatory bowel disease by administrating high-acetate-producing Saccharomyces cerevisae var. boulardii strains.

Productivity is a primary indicator when assessing plant communities or their responses to various stimuli, but it can be difficult and costly to determine. Adding to this complication is the retention of standing litter from previous years’ growth intermingled with current-year biomass. The most accurate and commonly applied method for estimating productivity is to clip and manually sort vegetation to separate current-year and previous years’ growth. Because sorting is costly, it is often only done for subsamples or not done at all. Without accounting for previous years’ growth, productivity estimates will be biased upward for conditions that accumulate more standing dead material, which is problematic when comparing treatments such as fire or different levels of herbivory. We tested whether line-point intercept methods could be adapted to determine proportions of current-year and older vegetation and estimate current-year biomass directly or by calculating the product of percent current-year intercepts and total standing crop. Data were collected by seven observers across four years and five experiments in northern mixed prairie using a total of 306 plots. Point-intercept transects with 20-cm spacing between points were used to determine number of intercepts for current-year and older vegetation and compared with data derived by clipping, manually sorting and weighing herbaceous vegetation. Regression analyses were used to test relationships between 1) total standing crop and total point intercepts; 2) current-year biomass and current-year point intercepts; 3) percent current-year biomass based on manual sorting versus point intercept methods; and 4) sorted current-year biomass and point intercept-derived current-year biomass. Number of intercepts per 100 points was positively related to total standing crop and current-year biomass, but r2 values were only 0.49 and 0.53. The relationship between manually-sorted current-year biomass and that derived from the product of point-intercept percentages and total standing crop was positive, explained 96 % of the variation, and had a mean absolute error of 122 kg ha−1. Point-intercept sampling is more efficient than manual sorting and can provide more indicators, including cover and diversity. Data indicate point intercept methods are accurate and can replace manual sorting of current-year herbaceous biomass.

A new aim for grassland management is to increase soil organic carbon (SOC) and to offset CO2 emissions by companies. This practice of carbon ranching may be informed by grazing-induced shifts in plant biomass and diversity which may foretell changes in SOC. Unfortunately, little is known about how grazing-induced shifts in plant properties correspond with shifts in SOC stocks. To help fill this gap, we used data from a field experiment to test whether above-ground plant properties (i.e. biomass, species richness) act as leading indicators of grazing-induced SOC accrual in the Northern Great Plains. The 5-yr bovine grazing experiment had a randomized complete block design and pre-treatment data. Moderate summer grazing (control) is widely used in the Northern Great Plains, and treatments that may alter grassland vegetation and SOC included: severe summer grazing, moderate fall grazing, and severe fall grazing. Severe fall and summer grazing increased SOC but had no effect on plant species richness and biomass relative to controls. Fall moderate grazing increased above-ground plant biomass but had no effect on SOC relative to controls. Changes to grazing practices can affect SOC without measurably affecting plant properties and can affect plant properties without measurably affecting SOC. While two drivers of SOC are plant carbon inputs and microbial respiration, our study indicates that grazing-induced change in above-ground vegetation is not predictive of change in SOC.

BackgroundIn February 2021, over one hundred scientists and policy experts participated in a web-based Workshop to discuss the ways that divergent evaluations of evidence and scientific uncertainties are used to delay timely protection of human health and the environment from exposures to hazardous agents. The Workshop arose from a previous workshop organized by the European Environment Agency (EEA) in 2008 and which also drew on case studies from the EEA reports on 'Late Lessons from Early Warnings' (2001, 2013). These reports documented dozens of hazardous agents including many chemicals, for which risk reduction measures were delayed for decades after scientists and others had issued early and later warnings about the harm likely to be caused by those agents.ResultsWorkshop participants used recent case studies including Perfluorooctanoic acid (PFOA), Extremely Low Frequency - Electrical Magnetic Fields (ELF-EMF fields), glyphosate, and Bisphenol A (BPA) to explore myriad reasons for divergent outcomes of evaluations, which has led to delayed and inadequate protection of the public's health. Strategies to overcome these barriers must, therefore, at a minimum include approaches that 1) Make better use of existing data and information, 2) Ensure timeliness, 3) Increase transparency, consistency and minimize bias in evidence evaluations, and 4) Minimize the influence of financial conflicts of interest.ConclusionThe recommendations should enhance the production of "actionable evidence," that is, reliable evaluations of the scientific evidence to support timely actions to protect health and environments from exposures to hazardous agents. The recommendations are applicable to policy and regulatory settings at the local, state, federal and international levels.

Abstract Background Real-world data on treatment patterns/outcomes for metastatic pancreatic cancer (mPAC) are limited. This study aims to assess real-world treatment patterns, survival outcomes, and prognostic/predictive factors in patients with mPAC. Methods Retrospective, observational, chart-review involving medical oncologists and gastroenterologists from five European countries. Physicians reported information on disease and patient characteristics, diagnosis, and treatment for patients diagnosed with mPAC from January-October 2016. Outcomes included median progression-free survival (mPFS), median overall survival (mOS), and the impact of baseline performance status on survival. Univariate/multivariate regression analyses were undertaken to identify prognostic/predictive factors. Results Three hundred four physicians and 3432 patients were included. First-line therapies included modified (m)FOLFIRINOX (28.4%), gemcitabine + nab-paclitaxel (28.0%), and gemcitabine monotherapy (23.0%). Frequent second-line therapies were gemcitabine monotherapy (25.0%), fluorouracil (5-FU) + oxaliplatin (21.8%), and gemcitabine + nab-paclitaxel (16.7%). Most frequent first- to second-line treatment sequences were gemcitabine + nab-paclitaxel followed by fluoropyrimidine combinations. Longest unadjusted estimated mOS was observed with (m)FOLFIRINOX followed by gemcitabine-based combinations (19.1 months). Multivariate analysis identified significant prognostic/predictive factors for OS and PFS including performance status and carbohydrate antigen 19–9 (CA 19–9) levels. Conclusions Treatment and treatment sequences were generally in accordance with guidelines at the time of the study. Identification of prognostic/predictive factors for survival may help inform the individualised management of mPAC patients in the future.

In this study the influence of fabric weave (plain, twill, and panama) and weft type (flax and hemp yarns) on selected mechanical and comfort properties of six fabrics was analyzed. The results showed that tear and abrasion properties were most affected by the weave. The tensile properties of the linen fabrics were not significantly different when weft hemp yarns were used instead of flax. Fabrics with the same weave seemed to be equally resilient to abrasion regardless of the type of weft. By contrast, the hemp weft yarns favorized the physical and comfort properties of the investigated fabrics. For the same weave, the hemp–linen fabrics were slightly lighter and exhibited lower bulk density, significantly larger air permeability, and improved moisture management properties. Although the results of maximum thermal flux (Qmax) suggested a cooler sensation of the linen fabrics with panama and twill, the hemp–linen fabric with a plain weave seemed to be the optimal choice when a cool sensation was desired. Higher thermal conductivity values also suggested slightly better heat transfer properties of the hemp–linen fabrics, and these were significantly influenced by the weave type. The results clearly indicated the advantages of using hemp for improving physical and specific comfort properties of linen fabrics.

γ-Secretase affects many physiological processes through targeting >100 substrates; malfunctioning links γ-secretase to cancer and Alzheimer's disease. The spatiotemporal regulation of its stoichiometric assembly remains unresolved. Fractionation, biochemical assays, and imaging support prior formation of stable dimers in the ER, which, after ER exit, assemble into full complexes. In vitro ER budding shows that none of the subunits is required for the exit of others. However, knockout of any subunit leads to the accumulation of incomplete subcomplexes in COPII vesicles. Mutating a DPE motif in presenilin 1 (PSEN1) abrogates ER exit of PSEN1 and PEN-2 but not nicastrin. We explain this by the preferential sorting of PSEN1 and nicastrin through Sec24A and Sec24C/D, respectively, arguing against full assembly before ER exit. Thus, dimeric subcomplexes aided by Sec24 paralog selectivity support a stepwise assembly of γ-secretase, controlling final levels in post-Golgi compartments.

Abstract Intermediate filaments (IFs) are essential constituents of the metazoan cytoskeleton. A vast family of cytoplasmic IF proteins are capable of self-assembly from soluble tetrameric species into typical 10–12 nm wide filaments. The primary structure of these proteins includes the signature central ‘rod’ domain of ~ 300 residues which forms a dimeric α-helical coiled coil composed of three segments (coil1A, coil1B and coil2) interconnected by non-helical, flexible linkers (L1 and L12). The rod is flanked by flexible terminal head and tail domains. At present, the molecular architecture of mature IFs is only poorly known, limiting our capacity to rationalize the effect of numerous disease-related mutations found in IF proteins. Here we addressed the molecular structure of soluble vimentin tetramers which are formed by two antiparallel, staggered dimers with coil1B domains aligned (A11 tetramers). By examining a series of progressive truncations, we show that the presence of the coil1A domain is essential for the tetramer formation. In addition, we employed a novel chemical cross-linking pipeline including isotope labelling to identify intra- and interdimeric cross-links within the tetramer. We conclude that the tetramer is synergistically stabilized by the interactions of the aligned coil1B domains, the interactions between coil1A and the N-terminal portion of coil2, and the electrostatic attraction between the oppositely charged head and rod domains. Our cross-linking data indicate that, starting with a straight A11 tetramer, flexibility of linkers L1 and L12 enables ‘backfolding’ of both the coil1A and coil2 domains onto the tetrameric core formed by the coil1B domains. Through additional small-angle X-ray scattering experiments we show that the elongated A11 tetramers dominate in low ionic strength solutions, while there is also a significant structural flexibility especially in the terminal domains.

Judith Wellens,1,2 Eva Vissers,1 Christophe Matthys,3,4 Séverine Vermeire,1,2 João Sabino1,2 1KU Leuven Department of Chronic Diseases and Metabolism, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium; 2Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium; 3Clinical Nutrition Unit, Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium; 4KU Leuven Department of Chronic Diseases and Metabolism, Clinical and Experimental Endocrinology, Leuven, BelgiumCorrespondence: João Sabino, Email joao.sabino@uzleuven.beAbstract: Inflammatory bowel diseases (IBD) are chronic and incurable conditions of the gastro-intestinal tract with an increasing incidence and prevalence worldwide. Common symptoms are abdominal pain, diarrhea, and weight loss. Despite recent advances in medical management, many patients fail to achieve clinical remission and healing of the mucosa of the bowel. The cause is thought to involve an inappropriate reaction of the immune system, the microbiome and the environment in genetically susceptible individuals, leading to chronic bowel inflammation. Evidence is emerging that diet is a key environmental factor that might influence disease onset and course, and therefore may become a therapeutic strategy to mitigate inflammation and symptoms. Since IBD is a heterogeneous disease on a clinical and a molecular level, personalizing dietary advice could be the crucial factor to achieve long-lasting changes in dietary behaviors that could not only improve nutritional status but also tackle gut inflammation and abdominal symptoms on an individual level. In this review, we first discuss different aspects of personalized nutrition, namely the level, focus, and scope of personalized dietary regimens. Then, we provide a framework for the different goals of nutritional therapy in IBD and current evidence for personalized dietary approaches. Lastly, we discuss the need for adequate trial designs, access to the right data types and the bioinformatic tools that are necessary to develop algorithms that will allow us to move from general “healthy eating” advice to truly personalized nutritional plans for the individual IBD patient.Keywords: inflammatory bowel disease, precision nutrition, nutritional therapy, personalized nutrition

Background: Since not all Crohn’s disease (CD) patients respond adequately to ustekinumab therapy, biomarkers could aid to monitor treatment response and optimize therapeutic outcomes. Objectives: To explore the dynamics of serum biomarker concentrations to monitor the response to ustekinumab treatment in CD patients. Design: Retrospective, exploratory study to evaluate concentrations of serum cytokines and acute phase proteins and their relation to endoscopic remission in CD patients during ustekinumab treatment. Methods: Serum concentrations of 16 proteins including cytokines and acute phase proteins were measured using the Mesoscale Discovery Platform in serum of healthy controls ( n = 13), and CD patients ( n = 61) at baseline (week 0), week 8 and week 24 during ustekinumab treatment. Endoscopic remission was defined as simple endoscopic score for CD (SES-CD)

Objective To infer potential mechanisms driving disease subtypes among patients with inflammatory bowel disease (IBD), we profiled the transcriptome of purified circulating monocytes and CD4 T-cells.Design RNA extracted from purified monocytes and CD4 T-cells derived from the peripheral blood of 125 endoscopically active patients with IBD was sequenced using Illumina HiSeq 4000NGS. We used complementary supervised and unsupervised analytical methods to infer gene expression signatures associated with demographic/clinical features. Expression differences and specificity were validated by comparison with publicly available single cell datasets, tissue-specific expression and meta-analyses. Drug target information, druggability and adverse reaction records were used to prioritise disease subtype-specific therapeutic targets.Results Unsupervised/supervised methods identified significant differences in the expression profiles of CD4 T-cells between patients with ileal Crohn’s disease (CD) and ulcerative colitis (UC). Following a pathway-based classification (Area Under Receiver Operating Characteristic - AUROC=86%) between ileal-CD and UC patients, we identified MAPK and FOXO pathways to be downregulated in UC. Coexpression module/regulatory network analysis using systems-biology approaches revealed mediatory core transcription factors. We independently confirmed that a subset of the disease location-associated signature is characterised by T-cell-specific and location-specific expression. Integration of drug-target information resulted in the discovery of several new (BCL6, GPR183, TNFAIP3) and repurposable drug targets (TUBB2A, PRKCQ) for ileal CD as well as novel targets (NAPEPLD, SLC35A1) for UC.Conclusions Transcriptomic profiling of circulating CD4 T-cells in patients with IBD demonstrated marked molecular differences between the IBD-spectrum extremities (UC and predominantly ileal CD, sandwiching colonic CD), which could help in prioritising particular drug targets for IBD subtypes.

Circulating antibody-secreting cells are present in the peripheral blood of healthy individuals reflecting the continued activity of the humoral immune system. Antibody-secreting cells typically express CD27. Here we describe and characterize a small population of antibody-secreting class switched CD19+CD43+ B cells that lack expression of CD27 in the peripheral blood of healthy subjects. In this study, we characterized CD27-CD43+ cells. We demonstrate that class-switched CD27-CD43+ B cells possess characteristics of conventional plasmablasts as they spontaneously secrete antibodies, are morphologically similar to antibody-secreting cells, show downregulation of B cell differentiation markers, and have a gene expression profile related to conventional plasmablasts. Despite these similarities, we observed differences in IgA and IgG subclass distribution, expression of homing markers, replication history, frequency of somatic hypermutation, immunoglobulin repertoire, gene expression related to Toll-like receptors, cytokines, and cytokine receptors, and antibody response to vaccination. Their frequency is altered in immune-mediated disorders.Conclusionwe characterized CD27-CD43+ cells as antibody-secreting cells with differences in function and homing potential as compared to conventional CD27+ antibody-secreting cells.

Abstract Background In February 2021, over one hundred scientists and policy experts participated in a web-based Workshop to discuss the ways that divergent evaluations of evidence and scientific uncertainties are used to delay timely protection of human health and the environment from exposures to hazardous agents. The Workshop arose from a previous workshop organized by the European Environment Agency (EEA) in 2008 and which also drew on case studies from the EEA reports on ‘Late Lessons from Early Warnings’ (2001, 2013). These reports documented dozens of hazardous agents including many chemicals, for which risk reduction measures were delayed for decades after scientists and others had issued early and later warnings about the harm likely to be caused by those agents. Results Workshop participants used recent case studies including Perfluorooctanoic acid (PFOA), Extremely Low Frequency – Electrical Magnetic Fields (ELF-EMF fields), glyphosate, and Bisphenol A (BPA) to explore myriad reasons for divergent outcomes of evaluations, which has led to delayed and inadequate protection of the public’s health. Strategies to overcome these barriers must, therefore, at a minimum include approaches that 1) Make better use of existing data and information, 2) Ensure timeliness, 3) Increase transparency, consistency and minimize bias in evidence evaluations, and 4) Minimize the influence of financial conflicts of interest. Conclusion The recommendations should enhance the production of “actionable evidence,” that is, reliable evaluations of the scientific evidence to support timely actions to protect health and environments from exposures to hazardous agents. The recommendations are applicable to policy and regulatory settings at the local, state, federal and international levels.

Background and Aims: Gastrointestinal (GI) endoscopy has known a great evolution in the last decades. Imaging techniques evolved from imaging with only standard white light endoscopes toward high-definition resolution endoscopes and the use of multiple color enhancement techniques, over to automated endoscopic assessment systems based on artificial intelligence. This narrative literature review aimed to provide a detailed overview on the latest evolutions within the field of advanced GI endoscopy, mainly focusing on the screening, diagnosis, and surveillance of common upper and lower GI pathology. Methods: This review comprises only literature about screening, diagnosis, and surveillance strategies using advanced endoscopic imaging techniques published in (inter)national peer-reviewed journals and written in English. Studies with only adult patients included were selected. A search was performed using MESH terms: dye-based chromoendoscopy, virtual chromoendoscopy, video enhancement technique, upper GI tract, lower GI tract, Barrett’s esophagus, esophageal squamous cell carcinoma, gastric cancer, colorectal polyps, inflammatory bowel disease, artificial intelligence. This review does not elaborate on the therapeutic application or impact of advanced GI endoscopy. Conclusions: Focusing on current and future applications and evolutions in the field of both upper and lower GI advanced endoscopy, this overview is a practical but detailed projection of the latest developments. Within this review, an active leap toward artificial intelligence and its recent developments in GI endoscopy was made. Additionally, the literature is weighted against the current international guidelines and assessed for its potential positive future impact.

Abstract The early detection of tissue and organ damage associated with autoimmune diseases (AID) has been identified as key to improve long-term survival, but non-invasive biomarkers are lacking. Elevated cell-free DNA (cfDNA) levels have been observed in AID and inflammatory bowel disease (IBD), prompting interest to use cfDNA as a potential non-invasive diagnostic and prognostic biomarker. Despite these known disease-related changes in concentration, it remains impossible to identify AID and IBD patients through cfDNA analysis alone. By using unsupervised clustering on large sets of shallow whole-genome sequencing (sWGS) cfDNA data, we uncover AID- and IBD-specific genome-wide patterns in plasma cfDNA in both the obstetric and general AID and IBD populations. We demonstrate that pregnant women with AID and IBD have higher odds of receiving inconclusive non-invasive prenatal screening (NIPS) results. Supervised learning of the genome-wide patterns allows AID prediction with 50% sensitivity at 95% specificity. Importantly, the method has the potential to identify pregnant women with AID during routine NIPS. Since AID pregnancies have an increased risk of severe complications, early recognition or detection of new-onset AID can redirect pregnancy management and limit potential adverse events. This method opens up new avenues for screening, diagnosis and monitoring of AID and IBD.