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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.

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.

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.

Background and Aims Radiological imaging is crucial for diagnosing and monitoring patients with inflammatory bowel diseases (IBD). With increasing awareness of radiation risks, imaging doses should be "as low as reasonably achievable," with a risk level that one should try to stay underneath 75 mSv. However, real-world data on cumulative exposure are limited. We retrospectively analyzed the radiation exposure of patients with IBD in a Belgian tertiary referral center. Methods Radiation exposure examinations were reviewed using the electronic health records. Annual (AED) and cumulative effective dose (CED) were calculated. A sub-analysis of patients diagnosed after January 1, 2007 was performed, as detailed radiation doses were maintained prospectively from that date onwards. Results In total, 4333 IBD patients (2753 Crohn's disease [CD], 1512 ulcerative colitis [UC]) were included. The median (Interquartile range [IQR]) AED was 0.47 (0.02-1.67) mSv/year, and higher in CD than in UC (0.59 [0.05-1.79] vs 0.28 [0.01-1.44] mSv/year, P  = .855). CED ≥ 75 mSv was reached in 5.5% of patients after a median [IQR] of 24 [13-34] years of follow-up. Sub-analysis of 1754 patients diagnosed from 2007 showed a median (IQR) AED of 0.74 (0.02-2.76) mSv/year, again higher for CD than UC (1.16 [0.02-3.42] vs 0.29 [0.01-2.28] mSv/year, P  = .189). Here, 3.3% reached a CED ≥ 75 mSv after a median (IQR) of 9 [6-12] years of follow-up. The most common reasons for radiation exposure were comorbidities like malignancy. Conclusions Up to 5.5% of IBD patients reached a CED ≥ 75 mSv. While most imaging decisions were deemed appropriate, caution against excessive radiation remains crucial. [ABSTRACT FROM AUTHOR]

Introduction It remains unclear why up to 30% of ulcerative colitis (UC) patients do not respond to tumor necrosis factor inhibitors (TNFi). Validated biomarkers for nonresponse (N)R) are lacking. Most studies investigating underlying mechanisms do not differentiate between pharmacokinetic and inflammatory mechanisms. We therefore aimed to develop a framework to correct for mucosal drug exposure (MDE) and applied this to mucosal cytokine profiles previously linked to (N)R. Methods In a prospective international cohort, we studied patients with active moderate–severe UC starting TNFi treatment. Patients underwent endoscopy before (baseline) and after induction treatment (follow-up). NR was defined as the absence of Mayo endoscopic subscore improvement by central read or need for colectomy. The ratio of mucosal concentrations of TNFi/TNF was used to define high or low MDE. Mucosal concentrations of interleukin-6 (IL-6), Oncostatin M (OSM), interleukin-10 (IL-10), and interleukin-12/23p40 (IL-12/IL-23p40) were measured. Results Fifty-four UC patients were included (43 infliximab, 11 adalimumab) of whom 39 (72%) were endoscopic responders (after a median treatment of 62 days [48–96]). NR with high MDE had high IL-6 at both time points. R with low MDE exhibited low mucosal IL-10 at baseline. At follow-up, high OSM was associated with NR (irrespective of MDE) and high IL-12/IL-23p40 with R. Conclusions We incorporated MDE in mucosal cytokine research to avoid bias due to the insufficient presence of anti-TNF. When applied to mucosal cytokines previously linked to (N)R, IL-6 appears to drive inflammation in TNFi-resistant UC patients, while OSM seems to parallel inflammation and does not cause refractoriness. [ABSTRACT FROM AUTHOR]

Background and Aims During early phases of inflammation, activated neutrophils extrude neutrophil extracellular traps (NETs) in a peptidyl arginine deiminase 4 (PAD4)-dependent manner, aggravating tissue injury and remodeling. In this study, we investigated the potential pro-fibrotic properties and signaling of NETs in Crohn's disease (CD). Methods NETs and activated fibroblasts were labeled on resected ileum from CD patients by multiplex immunofluorescence staining. NETs-treated human primary intestinal fibroblasts were analyzed by bulk RNA sequencing to uncover cell signaling pathways, and by high-throughput imaging to assess collagen production and migratory activity. Consequentially, TLR2/NF-κB pathway was evaluated by transfection of CCD-18Co fibroblasts with an NF-κB-luciferase reporter plasmid, incorporating C29 to block TLR2 signaling. A chronic dextran sulfate sodium (DSS) mouse model was used to define the specific role of PAD4 deletion in neutrophils (MRP8 -Cre, Pad4 fl/fl). Results Immunofluorescence showed spatial colocalization of NETs and activated fibroblasts in ileal ulcerations of CD patients. Transcriptomic analysis revealed upregulation of pro-fibrotic genes and activation of Toll-like receptor signaling pathways in NETs-treated fibroblasts. NETs treatment induced fibroblast proliferation, diminished migratory capability, and increased collagen release. Transfection experiments indicated a substantial increase in an NF-κB expression with NETs, whereas C29 led to decreased expression and release of collagen. In line, a significant reduction in collagen content was observed in the colon of MRP8 -Cre, Pad4 fl/fl mice subjected to chronic DSS colitis. Conclusions NETs potentially serve as an initial stimulus for pathological activation of fibroblasts within the intestine via the TLR2/NF-κB pathway. Given their early involvement in inflammation, inhibition of PAD4 might offer a strategy to modulate both inflammation and fibrogenesis in CD. [ABSTRACT FROM AUTHOR]

Background and Aims The ileum is the most commonly affected segment of the gastrointestinal tract in Crohn's disease [CD]. We aimed to determine whether disease location affects response to filgotinib, a Janus kinase [JAK] inhibitor, in patients with moderately-to-severely active Crohn's disease [CD] and applying appropriate methods to account for differences in measuring disease activity in the ileum compared with the colon. Methods This post-hoc analysis of data from the FITZROY phase 2 trial [NCT02048618] compared changes in the Crohn's Disease Activity Index [CDAI] and Simple Endoscopic Score for Crohn's Disease [SES-CD] among patients with ileal-dominant and isolated colonic CD treated with 10 weeks of filgotinib 200 mg daily or placebo. A mixed effects model for repeated measures was used to test whether ileal disease responded differently when compared with colonic disease, by evaluating for effect modification using the interaction term of treatment assignment-by-disease location. Results Numerically greater proportions of patients with isolated colonic disease compared to ileal-dominant CD achieved clinical remission [CDAI < 150, 75.9% vs 41.6%] and endoscopic response [SES-CD reduction by 50%, 52.5% vs 15.5%] at Week 10. However, after adjusting for baseline disease activity by disease location and within-patient clustering effects, there was no significant difference in treatment response by disease location [mean difference in ΔCDAI between ileal-dominant vs isolated colonic disease + 9.24 [95% CI: -87.19, +105.67], p  = 0.85; mean difference in ΔSES-CD -1.93 [95% CI: -7.03, +3.44], p  = 0.48. Conclusions Filgotinib demonstrated similar efficacy in ileal-dominant and isolated colonic CD when controlling for baseline disease activity and clustering effects. [ABSTRACT FROM AUTHOR]

Background Clinical trial recruitment for patients with inflammatory bowel disease [IBD] has become more challenging over time. We aimed to develop recommendations for broadening IBD clinical trial eligibility, to improve the inclusion of a more representative patient population in a more efficient timeline. Methods We applied the RAND/UCLA Appropriateness Method, focused on broadening IBD clinical trial eligibility. A literature review was performed for seven domains, each representing a different area related to trial recruitment. Based on these domains, 32 statements were developed. A questionnaire was sent to IBD specialists so as to anonymously vote on each statement with regards to its appropriateness and feasibility. After the first round of voting, participants met for a moderated discussion to review all statements. At the end of the discussion, a second round of anonymous voting led to the final recommendations. Results The final round of voting resulted in 26 statements. All were rated as feasible and 25 of 26 rated as appropriate. Recommendations generally are to be more inclusive of complicated disease phenotypes, more liberal around safety criteria, to recognise the importance of non-invasive imaging and biomarkers, to minimise the washout period and to not enforce a minimum or maximum number of prior medications, to allow a recently recorded colonoscopy to count as a baseline study, and to be less restrictive of age. Conclusion Recommendations to broaden clinical trial eligibility were found to be both appropriate and feasible, with a high degree of agreement amongst an international group of IBD specialists. [ABSTRACT FROM AUTHOR]

In arid and semiarid systems of western North America, the most damaging invasive plants are winter annuals. These plants are destroying wildlife habitat, reducing livestock production, and increasing wildfires. Monitoring these plants for lasting population changes is challenging because their abundances vary widely from year to year. Some of this variation is due to weather, and quantifying effects of weather is important for distinguishing transcient from lasting population changes and understanding effects of climate change. Fall and spring weather affect germination and seed production of the current generation of plants and, therefore, impact population sizes of subsequent generations of plants. Extensive data are required to estimate effects of fall and spring weather on multiple generations of plants. We used Bayesian statistics to integrate experimental and long‐term (31 years) monitoring data and quantify invasive annual grass [downy brome (Bromus tectorum L.) and Japanese brome (Bromus japonicus Thunb.)] responses to weather. Bromes ranged from nearly absent to comprising half of total biomass depending on three previous years of weather. Brome biomass increased with precipitation one, two, and three falls prior to measurement. Fall precipitation is projected to increase, and a mere 6.5 mm increase, which is just 2% of mean annual precipitation, would increase brome biomass 40% (28%, 54%) (mean [95% CI]) according to our model. Increased fall precipitation could favor many invasive winter annual grasses and forbs. Dry spring conditions reduced brome biomass the current year but increased brome biomass one and likely two (p = 0.08) years later, perhaps because dry conditions weakened perennial competitors. This finding casts doubt on several one‐year precipitation experiments that concluded drier spring weather would reduce brome abundances. Integrating short‐term experiments and long‐term monitoring is useful for estimating invasive plant responses to the weather and characterizing their responses to climate change. Our research provides predictions of brome abundances that could improve monitoring efforts by helping land managers interpret population dynamics in the context of seasonal precipitation patterns. [ABSTRACT FROM AUTHOR]

Seventeen percent of patients with ulcerative colitis that undergo proctocolectomy with pouch surgery will develop chronic pouchitis. W e evaluated the efficacy of ustekinumab for these patients. We performed a prospective study of patients with chronic pouchitis receiving ustekinumab intravenously at baseline (∼6 mg/kg) and 90 mg ustekinumab subcutaneously every 8 weeks thereafter. The Modified Pouchitis Disease Activity Index (mPDAI) was assessed at baseline and weeks 16 and 48. The primary endpoint was the proportion of patients achieving steroid-free remission (mPDAI <5 and reduction by ≥2 points) at week 16. Secondary endpoints included the proportion of patients achieving remission at week 48, the proportion of patients achieving response (reduction of mPDAI by ≥2 points) at weeks 16 and 48, and change in mPDAI. We enrolled 22 patients (59% male; median age, 42.2 years). Remission was achieved in 27.3% at week 16 and 36.4% at week 48. Response was achieved in 54.5% both at weeks 16 and 48. The median mPDAI decreased from 8 (interquartile range [IQR], 7–10) to 7 (IQR, 4–9) at week 16 (P =.007) and 4 (IQR, 1.75–7.25) at week 48 (P <.001). The clinical mPDAI subscore decreased from 3.5 (IQR, 2–4) to 2 (IQR, 1–3) at week 16 (P =.009) and 1 (IQR, 0–2.25) at week 48 (P =.001). The endoscopic mPDAI subscore decreased from 5.5 (IQR, 4–6) to 4 (IQR, 3–6) at week 16 (P =.032) and 3 (IQR, 1.75–4.25) at week 48 (P =.001). Ustekinumab was efficacious in one-half of the patients suffering from chronic pouchitis. Ustekinumab should therefore be positioned in the treatment algorithm of chronic pouchitis. (ClinicalTrials.gov Number NCT04089345) [ABSTRACT FROM AUTHOR]

UNLABELLED: Interferon (IFN) inhibits HIV replication by inducing antiviral effectors. To comprehensively identify IFN-induced HIV restriction factors, we assembled a CRISPR sgRNA library of Interferon Stimulated Genes (ISGs) into a modified lentiviral vector that allows for packaging of sgRNA-encoding genomes in trans into budding HIV-1 particles. We observed that knockout of Zinc Antiviral Protein (ZAP) improved the performance of the screen due to ZAP-mediated inhibition of the vector. A small panel of IFN-induced HIV restriction factors, including MxB, IFITM1, Tetherin/BST2 and TRIM5alpha together explain the inhibitory effects of IFN on the CXCR4-tropic HIV-1 strain, HIV-1LAI, in THP-1 cells. A second screen with a CCR5-tropic primary strain, HIV-1Q23.BG505, described an overlapping, but non-identical, panel of restriction factors. Further, this screen also identifies HIV dependency factors. The ability of IFN-induced restriction factors to inhibit HIV strains to replicate in human cells suggests that these human restriction factors are incompletely antagonized. EDITORIAL NOTE: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editors assessment is that all the issues have been addressed (see decision letter).

Herbivores alter plant biodiversity (species richness) in many of the world's ecosystems, but the magnitude and the direction of herbivore effects on biodiversity vary widely within and among ecosystems. One current theory predicts that herbivores enhance plant biodiversity at high productivity but have the opposite effect at low productivity. Yet, empirical support for the importance of site productivity as a mediator of these herbivore impacts is equivocal. Here, we synthesize data from 252 large-herbivore exclusion studies, spanning a 20-fold range in site productivity, to test an alternative hypothesis-that herbivore-induced changes in the competitive environment determine the response of plant biodiversity to herbivory irrespective of productivity. Under this hypothesis, when herbivores reduce the abundance (biomass, cover) of dominant species (for example, because the dominant plant is palatable), additional resources become available to support new species, thereby increasing biodiversity. By contrast, if herbivores promote high dominance by increasing the abundance of herbivory-resistant, unpalatable species, then resource availability for other species decreases reducing biodiversity. We show that herbivore-induced change in dominance, independent of site productivity or precipitation (a proxy for productivity), is the best predictor of herbivore effects on biodiversity in grassland and savannah sites. Given that most herbaceous ecosystems are dominated by one or a few species, altering the competitive environment via herbivores or by other means may be an effective strategy for conserving biodiversity in grasslands and savannahs globally.

Fractionation of soil organic carbon (SOC) is crucial for mechanistic understanding and modeling of soil organic matter decomposition and stabilization processes. It is often aimed at separating the bulk SOC into fractions with varying turnover rates, but a comprehensive comparison of methods to achieve this is lacking. In this study, a total of 20 different SOC fractionation methods were tested by participating laboratories for their suitability to isolate fractions with varying turnover rates, using agricultural soils from three experimental sites with vegetation change from C3 to C4 22–36 years ago. Enrichment of C4-derived carbon was traced and used as a proxy for turnover rates in the fractions. Methods that apply a combination of physical (density, size) and chemical (oxidation, extraction) fractionation were identified as most effective in separating SOC into fractions with distinct turnover rates. Coarse light SOC separated by density fractionation was the most C4-carbon enriched fraction, while oxidation-resistant SOC left after extraction with NaOCl was the least C4-carbon enriched fraction. Surprisingly, even after 36 years of C4 crop cultivation in a temperate climate, no method was able to isolate a fraction with more than 76% turnover, which challenges the link to the most active plant-derived carbon pools in models. Particles with density >2.8 g cm−3 showed similar C4-carbon enrichment as oxidation-resistant SOC, highlighting the importance of sesquioxides for SOC stabilization. The importance of clay and silt-sized particles (

Fractionation of soil organic carbon (SOC) is crucial for mechanistic understanding and modeling of soil organic matter decomposition and stabilization processes. It is often aimed at separating the bulk SOC into fractions with varying turnover rates, but a comprehensive comparison of methods to achieve this is lacking. In this study, a total of 20 different SOC fractionation methods were tested by participating laboratories for their suitability to isolate fractions with varying turnover rates, using agricultural soils from three experimental sites with vegetation change from C3 to C4 22–36 years ago. Enrichment of C4-derived carbon was traced and used as a proxy for turnover rates in the fractions. Methods that apply a combination of physical (density, size) and chemical (oxidation, extraction) fractionation were identified as most effective in separating SOC into fractions with distinct turnover rates. Coarse light SOC separated by density fractionation was the most C4-carbon enriched fraction, while oxidation-resistant SOC left after extraction with NaOCl was the least C4-carbon enriched fraction. Surprisingly, even after 36 years of C4 crop cultivation in a temperate climate, no method was able to isolate a fraction with more than 76% turnover, which challenges the link to the most active plant-derived carbon pools in models. Particles with density >2.8 g cm−3 showed similar C4-carbon enrichment as oxidation-resistant SOC, highlighting the importance of sesquioxides for SOC stabilization. The importance of clay and silt-sized particles (