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State legislation serves as a guide and critical influence on the evaluation and identification of students with dyslexia across the United States. The state of Texas has numerous laws and regulations concerning dyslexia, guided by the Texas Administrative Code, Texas Education Code, Texas Occupations Code, and the Texas Education Agency's dyslexia handbook (National Center on Improving Literacy [NCIL], 2021). This article is an analysis of publicly available statewide data to assess the impact federal and state legislative policies have had on the prevalence rate of students with dyslexia in 839 urban and rural school districts in Texas. 839 school districts from the 2016-2017 to 2022-2023 school years were extracted from the Texas Education Agency's Public Education Information Management System. Researchers focused on the Office of Special Education Programs (OSEP) Corrective Action to the TEA (OSEP, 2018), the TEA state dyslexia handbook revisions (TEA, 2021), and the unique prevalence of rural school districts in Texas (Simmons et al., 2021). Analysis focused on implications for dyslexia evaluation and identification practices for school districts and evaluators within the state.

This article considers the value of honors education beyond its marked contributions to enrollment management goals. Suggesting that quantitative assessments toward understanding the value of honors fail to capture its breadth, interdisciplinary focus, and engagement, authors posit a new way of measuring impacts from "contagion model" (spillover to campus and beyond) to "permeability model" (interface across campus). Pointing to the benefits of permeability for both honors and the broader campus communities, authors encourage practitioners to foster exchange in curricular offerings, spatial inputs, scholarly outputs, extramural funding, and institutional support. The meaning and history of organizational permeability is explored, and examples are provided.

Abstract Increasing studies have investigated the link between physical activity (PA) and sedentary behavior with venous thromboembolism (VTE) but the existing findings are not consistent and the independent relationship is uncertain. This meta-analysis aimed to comprehensively assess the shape of dose-response relationship between PA and sedentary behavior with VTE and further explore whether the relationship is independent after mutual adjustment. We systematically searched PubMed, Embase and Web of Science from inception to August 1, 2024. PA exposures were converted into MET-h/wk. Categorical meta-analyses and a cubic spline model were performed to evaluate the association between PA, sedentary behavior and VTE. Twenty-five articles including 31 studies were included. A curvilinear dose-response relationship between PA and VTE was observed, with steeper gradients even at lower PA levels. After adjustment for sedentary behavior, higher level of PA was independently associated with a reduced VTE risk (OR = 0.83, 95%CI:0.77–0.89). Based on population attributable fraction analyses, 2.37% (95%CI: 1.90-2.85%) of incident VTE could have been prevented if all adults had achieved half the PA minimum recommended level. A linear dose-response relationship between sedentary behavior and VTE risk was found, and there was a 2% higher risk of VTE (OR = 1.02, 95%CI: 1.00-1.03) for 1 h increment of sedentary behavior per day. After adjustment for PA, sedentary behavior was independently associated with an increased VTE risk (OR = 1.19, 95CI%:1.01–1.39). Our analyses demonstrated PA and sedentary time were indeed independently associated with the risk of VTE after mutually adjusting for sedentary time or PA, highlighting a unique perspective on their individual contributions. Further studies assessing the effects of different combinations of PA and sedentary time for assessing joint effects on VTE are needed.

Objective: The current study examined group differences in college students' views on e-cigarettes in terms of safety, popularity, health risks, social acceptability, efficacy as a cessation aid, and promoting combustible cigarette use. Participants: 337 undergraduates (M[subscript age] = 20.84, SD = 3.79; 72.1% female; 68.5% White) divided into three groups: Never Users (n = 178), Ever Users (n = 108), and Current Users (n = 51). Methods: Participants completed questionnaires for course credit. Results: Compared to Ever and Never Users, Current Users believed e-cigarettes were safer, healthier, a useful tool to quit smoking, did not lead to combustible cigarette smoking, and that nicotine was less dangerous. Current Users also were less likely to endorse boosting social image as a motive for use. Conclusions: Public health campaigns could benefit from targeting current users' positive beliefs about e-cigarettes to reduce the prevalence of e-cigarette use among college students.

Objective: Discrimination is a social determinant contributing to health inequities in the United States (US). This study investigated the prevalence of, and sociodemographic disparities in, perceived everyday discrimination among a national sample of US adults. Methods: We used data from the 2023 National Health Interview Survey (n = 27,538) and estimated the prevalence of three perceived everyday discrimination outcomes (1) any discrimination, (2) unique components of the discrimination experience, and (3) the Everyday Discrimination Scale (EDS) (range: 0–20) overall and by age, sex assigned at birth, race and ethnicity, sexual orientation, educational attainment, income-to-poverty ratio, and urban-rural status. Results: Over half of US adults experienced any discrimination (55.8 %), and the most common form of perceived discrimination was being treated with less respect (45.2 %). Adults who were younger (aged 18–44), female, non-Hispanic Black, sexual minority, some college-educated, low income, or urban-living generally reported higher discrimination. For example, among the sample, non-Hispanic Black (vs. non-Hispanic White) (OR: 1.61, 95 % CI: 1.44–1.81) and sexual minority (vs. heterosexual) (OR: 2.48, 95 % CI: 2.12–2.90) adults had the highest odds of any discrimination and EDS scores (β: 1.38 (95 % CI: 1.17–1.59) and β: 1.65 (95 % CI: 1.35–1.94), respectively). The odds of perceived discrimination varied in magnitude by specific experience; for example, sexual minority adults had the highest odds of being threatened or harassed (OR: 2.93, 95 % CI: 2.52–3.42). Conclusions: Perceived everyday discrimination is prevalent and differentially affects adults, especially members of marginalized and underserved populations. Understanding discrimination patterns will benefit public health and medical efforts aimed at mitigating exposure and deleterious health consequences.

Practice variability may represent an opportunity to improve care by identifying the differences in outcomes associated with differences in practice. To characterize differences in depression treatment outcomes among individual providers in outpatient psychiatry practices and primary care practices, we examined a longitudinal cohort derived from outpatient electronic health records from two academic medical centers and six community hospitals in Eastern Massachusetts. This cohort included antidepressant-treated individuals with an ICD-9/10 diagnosis of major depressive disorder, and deidentified health care providers treating at least 10 such patients per year between 2008 and 2022. We examined the association between individual provider prescribing characteristics and proportions of treated patients who do not follow up after initial antidepressant prescription or who achieve a stable ongoing prescription. In binomial regression models, among 104 psychiatrists, greater heterogeneity in antidepressant prescribing and lesser proportion of serotonin reuptake inhibitors (SSRIs)1 prescribed were associated with greater rates of achieving stability (for heterogeneity, adjusted odds ratio AOR, 1.55 [95 % CI, 1.22 – 2.06]; for proportion of SSRIs, AOR, 0.01 [95 % CI, 0.00–0.59]). Among 369 primary care physicians, greater volume of depression encounters per year, but not prescribing heterogeneity, was associated with greater rates of achieving stability (for encounters, AOR, 2.15 [95 % CI, 1.61 – 2.89]; for heterogeneity, AOR, 0.99 [95 % CI, 0.85 – 1.15]). Primary care and psychiatry predictors are not the same and therefore suggest potentially distinct strategies to improve clinical outcomes in each setting. Trial Registration: N/A

Abstract In situ Electron Energy Loss Spectroscopy (EELS) combined with Transmission Electron Microscopy (TEM) has traditionally been pivotal for understanding how material processing choices affect local structure and composition. However, the ability to monitor and respond to ultrafast transient changes, now achievable with EELS and TEM, necessitates innovative analytical frameworks. Here, we introduce a machine learning (ML) framework tailored for the real-time assessment and characterization of in operando EELS Spectrum Images (EELS-SI). We focus on 2D MXenes as the sample material system, specifically targeting the understanding and control of their atomic-scale structural transformations that critically influence their electronic and optical properties. This approach requires fewer labeled training data points than typical deep learning classification methods. By integrating computationally generated structures of MXenes and experimental datasets into a unified latent space using Variational Autoencoders (VAE) in a unique training method, our framework accurately predicts structural evolutions at latencies pertinent to closed-loop processing within the TEM. This study presents a critical advancement in enabling automated, on-the-fly synthesis and characterization, significantly enhancing capabilities for materials discovery and the precision engineering of functional materials at the atomic scale.

A new set of standalone parameterizations is presented for simulating the injection, evolution, and radiative forcing by stratospheric volcanic aerosols against an idealized Held–Suarez–Williamson (HSW) atmospheric background in the Energy Exascale Earth System Model version 2 (E3SMv2). In this model configuration (HSW with enabled volcanism, HSW-V), sulfur dioxide (SO2) and ash are injected into the atmosphere with a specified profile in the vertical, and they proceed to follow a simple exponential decay. The SO2 decay is modeled as a perfect conversion to a long-living sulfate aerosol which persists in the stratosphere. All three species are implemented as tracers in the model framework and are transported by the dynamical core's advection algorithm. The aerosols contribute simultaneously to local heating of the stratosphere and cooling of the surface by a simple plane-parallel Beer–Lambert law applied on two zonally symmetric radiation broadbands in the longwave and shortwave ranges. It is shown that the implementation parameters can be tuned to produce realistic temperature anomaly signatures of large volcanic events. In particular, results are shown for an ensemble of runs that mimic the volcanic eruption of Mt. Pinatubo in 1991. The design requires no coupling to microphysical subgrid-scale parameterizations and thus approaches the computational affordability of prescribed aerosol forcing strategies. The idealized simulations contain a single isolated volcanic event against a statistically uniform climate, where no background aerosols or other sources of externally forced variability are present. HSW-V represents a simpler-to-understand tool for the development of climate source-to-impact attribution methods.

Abstract Topological materials confined in 1D can transform computing technologies, such as 1D topological semimetals for nanoscale interconnects and 1D topological superconductors for fault-tolerant quantum computing. As such, understanding crystallization of 1D-confined topological materials is critical. Here, we demonstrate 1D template-assisted nanowire synthesis where we observe diameter-dependent phase selectivity for tungsten phosphides. A phase bifurcation occurs to produce tungsten monophosphide and tungsten diphosphide at the cross-over nanowire diameter regime of 35–70 nm. Four-dimensional scanning transmission electron microscopy is used to identify the two phases and to map crystallographic orientations of grains at a few nm resolution. The 1D-confined phase selectivity is attributed to the minimization of the total surface energy, which depends on the nanowire diameter and chemical potentials of precursors. Theoretical calculations are carried out to construct the diameter-dependent phase diagram, which agrees with experimental observations. Our findings suggest a crystallization route to stabilize topological materials confined in 1D.

Introduction Perianal fistulising Crohn’s disease (pfCD) is a distinct and debilitating phenotype seen in around one-third of patients with CD. Clinical trials in pfCD are increasingly using magnetic resonance imaging (MRI) criteria as a primary endpoint, but there is heterogeneity in the radiological definition of a healed perianal fistula that currently limits our ability to perform meaningful meta-analyses of studies. Our aim is to standardise outcomes through the generation of an international consensus definition of a radiologically healed fistula.Methods and analysis This international Delphi consensus study employs a two-part strategy.The first is a systematic review to identify a longlist of variables used to define radiological healing in pfCD. MRI-based indices used to score fistula severity and healing will be assessed for their methodological quality using Consensus-based Standards for the selection of health Measurement Instruments (COSMIN). The systematic review protocol will be conducted using COSMIN methodology and reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses.The second part will be an online Delphi consensus, guided by the results of the systematic review. Radiologists, gastroenterologists and colorectal surgeons with expertise in the management of pfCD will be invited to take part in two to three rounds of online surveys. Once an a priori threshold of >80% agreement is reached on individual radiological components used to define ‘healing’ and ‘healed’, a final meeting of key stakeholders will be organised to generate a consensus definition of a healed fistula.Ethics and dissemination The study has been deemed exempt from a formal Research Ethics Committee review as no patients will participate directly in the consensus process, given the technical nature of the research question. The study is registered with the local R&D department (Reference RD24/007). Publication of this study will help standardise radiological endpoint measurement in clinical trials of pfCD and improve the synthesis and meta-analysis of comparative studies.PROSPERO registration number CRD42024504334.

Introduction: Both electronic cigarette (e-cigarette) and social media use among youth are public health concerns. While the health impacts of extensive social media use and frequent use of e-cigarettes have been discussed independently in the literature, little is known about the relationship between the two. This study aims to examine the potential association between extensive social media use and the frequency of current, e-cigarette use among United States (US) youth. Methods: Data from the 2022 National Youth Tobacco Survey (NYTS) were analyzed. The sample included 23,655 middle and high school students aged 9–18 years. Frequency of current e-cigarette use was categorized based on past-30 day use (i.e., never/former, 1–9 days, 10–29 days, or 30 days). Social media use was dichotomized into less than 4 hours daily and 4+ hours daily (i.e., extensive use). Multivariable multinomial logistic regression estimated the relationship between social media use and e-cigarette use frequency. Results: Over one-third (35.8 %) of youth used social media extensively and 8.6 % reported current use of e-cigarettes. Extensive social media use was associated with daily e-cigarette use (OR: 1.94, 95 % CI: 1.48–2.56) but not with other use categories. Older age, female sex, lower grades, current other tobacco use, and family tobacco use were also associated with daily e-cigarette use. Conclusions: Extensive social media use is associated with daily e-cigarette use among US youth. Public health interventions should consider the influence of social media on tobacco use behaviors and tailor prevention strategies to address this potential modifiable risk factor.

Introduction: Cannabis use is increasing due to several factors including the adoption of laws legalizing its use across the United States (US). We examined changes in current cannabis use among US youth and adults and by key sociodemographic groups. Methods: Using data from the 2013–2022 National Survey on Drug Use and Health (n=543,195), we estimated the prevalence of (2013–2019, 2020, 2021–2022) and trends in (2013–2019, 2021–2022) current (i.e., past 30-day) cannabis use among US youth (aged 12–17) and adults (aged 18+) overall and by age, gender, race and ethnicity, educational attainment, and total annual family income. We also examined sociodemographic factors associated with use from 2013 to 2019, in 2020, and from 2021 to 2022. Results: Cannabis use increased from 7.59 % to 11.48 % in 2013–2019, was 11.54 % in 2020, and increased again from 13.13 % to 15.11 % in 2021–2022. Among youth, cannabis use remained constant from 2013 to 2019 and 2021–2022. In 2022, use was highest among aged 18–34, male, non-Hispanic multiracial, and generally lower SES adults. From 2021–2022, cannabis use increased among several groups such as adults who were aged 35–49 (14.25–17.23 %), female (11.21–13.00 %), and Hispanic (10.42–13.50 %). Adults who were aged 18–25, male, non-Hispanic multiracial, some college educated, and of lower annual family income had consistently higher odds of current cannabis use from 2013 to 2019, in 2020, and from 2021 to 2022. Conclusions: Cannabis use is increasing overall and among certain sociodemographic groups. Our findings inform prevention and harm reduction efforts aimed at mitigating the prevalence of cannabis use in the US.

Abstract Background Pulmonary ionocytes have been identified in the airway epithelium as a small population of ion transporting cells expressing high levels of CFTR (cystic fibrosis transmembrane conductance regulator), the gene mutated in cystic fibrosis. By providing an infinite source of airway epithelial cells (AECs), the use of human induced pluripotent stem cells (hiPSCs) could overcome some challenges of studying ionocytes. However, the production of AEC epithelia containing ionocytes from hiPSCs has proven difficult. Here, we present a platform to produce hiPSC-derived AECs (hiPSC-AECs) including ionocytes and investigate their role in the airway epithelium. Methods hiPSCs were differentiated into lung progenitors, which were expanded as 3D organoids and matured by air-liquid interface culture as polarised hiPSC-AEC epithelia. Using CRISPR/Cas9 technology, we generated a hiPSCs knockout (KO) for FOXI1, a transcription factor that is essential for ionocyte specification. Differences between FOXI1 KO hiPSC-AECs and their wild-type (WT) isogenic controls were investigated by assessing gene and protein expression, epithelial composition, cilia coverage and motility, pH and transepithelial barrier properties. Results Mature hiPSC-AEC epithelia contained basal cells, secretory cells, ciliated cells with motile cilia, pulmonary neuroendocrine cells (PNECs) and ionocytes. There was no difference between FOXI1 WT and KO hiPSCs in terms of their capacity to differentiate into airway progenitors. However, FOXI1 KO led to mature hiPSC-AEC epithelia without ionocytes with reduced capacity to produce ciliated cells. Conclusion Our results suggest that ionocytes could have role beyond transepithelial ion transport by regulating epithelial properties and homeostasis in the airway epithelium.

Background Ulcerative colitis is an autoimmune reaction to imbalanced colonic microbiome in genetically predisposed patients. There have been four published randomised controlled trials of faecal microbiota transplant versus placebo in ulcerative colitis; three being positive. However, the methodology used varied and mechanistic data were sparse. Objective To identify an optimal faecal microbiota transplant delivery route to test in a future efficacy-powered randomised controlled trial. Design Prospective, multicentre, open-label, parallel-group, randomised pilot study. Participants were randomised in a 1 : 1 ratio to faecal microbiota transplant by nasogastric or by colonoscopy, minimised by partial Mayo score and current smoking status. Setting Three secondary care hospitals in the United Kingdom. Participants Thirty adult patients with mild to moderately active ulcerative colitis (partial Mayo score of ≥4 and ≤8). Interventions Faecal microbiota transplant samples were prepared at the University of Birmingham Microbiome Treatment Centre and administered to participants either via a nasogastric tube on 4 consecutive days repeated after a month (nasogastric) or by colonoscopy followed by 7 weekly enemas (COLON). Each treatment course was from a single matched donor. Participants and researchers underwent qualitative interviews regarding the faecal microbiota transplant experience. Main outcome measure Composite assessment of qualitative and quantitative data based on efficacy, acceptability and safety. Clinical response (primary measure of efficacy) was defined as a ≥3 point and ≥30% reduction in full Mayo score from randomisation to week 8 and a ≥1 point reduction in rectal bleeding subscore or absolute rectal bleeding subscore of 0 or 1. Results Thirty ulcerative colitis patients were randomised: 16 to nasogastric; 14 to COLON. Seven participants in the nasogastric arm and two in the COLON arm withdrew from treatment and clinical follow-up. Eight of 16 (50%) nasogastric participants were adherent compared to 12/14 (86%) COLON participants. Clinical response data were available for 20 of 30 randomised participants. Clinical response was seen in 2/8 (25%) nasogastric participants versus 9/12 (75%) COLON participants: adjusted risk ratio 2.94 (95% CI 0.84 to 10.30). Adverse events were reported in 11/16 (69%) nasogastric participants versus 11/14 (79%) COLON participants. There were three serious adverse events in two nasogastric participants. Faecal microbiota transplant was deemed an acceptable treatment for ulcerative colitis, with greater participant and clinician acceptability for the COLON route. Faecal microbiota transplant responders had a greater reduction in faecal calprotectin compared to non-responders (t-test p = 0.03) and increase in faecal microbiome diversity (Shannon diversity p < 0.01). In the whole cohort, a negative association between faecal calprotectin and diversity was seen (Kendall’s tau z = −2.8231, p = 0.004757). There were increases in faecal acetate (p = 0.05) and butyrate (p = 0.03) after faecal microbiota transplant intervention, but these were not associated with clinical response. A limitation was that this was an open-label pilot study, which was not powered to assess for efficacy of faecal microbiota transplant. Conclusions Faecal microbiota transplant delivered by the colonic route was considered safe and better tolerated than the nasogastric route. The colonic route was preferred by both participants and clinicians. Mechanistic signals indicated reduction in colonic inflammation and increased microbiome diversity in faecal microbiota transplant responders. Future work An efficacy-powered randomised controlled trial. Trial registration This trial is registered as ISRCTN74072945 and EudraCT 2015-005753-12. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 13/179/01) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 14. See the NIHR Funding and Awards website for further award information. Plain language summary Ulcerative colitis, a chronic inflammatory condition affecting the colon, results from the body’s immune response to imbalance in colonic microbes (microbiota). Faecal microbiota transplantation involves transferring processed donated stool samples from carefully screened healthy donors to ulcerative colitis patients aiming to correct the imbalance and reduce inflammation. There have been four trials comparing faecal microbiota transplant with placebo (dummy no treatment) to treat ulcerative colitis, and one which investigated faecal microbiota transplant with dietary intervention. Three of these studies showed encouraging benefit for faecal microbiota transplant. However, these studies varied in the methods used, with faecal microbiota transplant delivered either to the stomach or colon, or both. The aim of this study was to identify the best route of faecal microbiota transplant administration before undertaking a large-scale trial comparing faecal microbiota transplant with placebo. Between March 2018 and 30 April 2019 ulcerative colitis patients from three hospitals were randomly allocated to receive faecal microbiota transplant via either a tube inserted through the nose into the stomach on 4 consecutive days repeated after a month (nasogastric group; 16 participants) or by colonoscopy followed by 7 weekly enemas (COLON group; 14 participants). Faecal microbiota transplant was well accepted, with both patients with ulcerative colitis and healthcare staff stating a preference for the colonic route. Only 8 of 16 in the nasogastric group completed the study compared to 12 of 14 in the COLON group. Altogether, 9/12 (75%) in the COLON group improved compared with 2/8 (25%) in the nasogastric group. The majority of participants [11/14 (79%) COLON vs. 11/16 (69%) nasogastric] had mild, short-lived side effects following faecal microbiota transplant. There were three serious adverse events. Faecal calprotectin (indicating colonic inflammation) fell in responders and stool samples showed an increase in the number of microbial species after faecal microbiota transplant. At the end of the study, a recommendation was made by the Independent Oversight Committee to proceed to a large placebo-controlled randomised trial using the colonic route. Scientific summary Background Ulcerative colitis (UC) results from an exaggerated immune response to an imbalanced (dysbiotic) colonic microbiome in genetically predisposed patients. At the inception of this study, there had been four published randomised controlled trials (RCTs) comparing faecal microbiota transplantation (FMT) with placebo to treat UC in adults. Of these four seminal studies, three involved delivery of FMT via the colonic route and one a combination of delivery to the foregut and colon. This latter study was the only one of the four not to show a difference in efficacy compared to placebo. Foregut-delivered FMT is extensively and successfully used in clinical practice to treat Clostridioides difficile infection (CDI). From the results of the UC trials, FMT appeared to have therapeutic potential for UC. However, the methodology employed in these studies was varied and, taking into account the efficacy of FMT delivered to the foregut to treat CDI, there was uncertainty regarding the best route of delivery in the context of UC. Objectives The aims of this pilot study were as follows: to determine which FMT administration route [nasogastric (NG) or colonic (COLON)] should be investigated in a randomised double-blind, placebo-controlled trial to determine whether a full-scale RCT was feasible. In order to achieve these aims, the pilot study had the following clinical objectives. To assess the following: whether FMT by the NG route induces clinical response in patients with active UC whether FMT by the COLON route induces clinical response in patients with active UC tolerability and safety which route of FMT delivery (if any) was suitable to investigate in a full-scale RCT. The aims of the qualitative research were to assess the following: patient and clinician acceptability of FMT (NG route) patient and clinician acceptability of FMT (COLON route). The aims of the nested-mechanistic substudy were to assess the following: whether FMT by either route is associated with a change in faecal calprotectin as a surrogate marker of colonic inflammation changes in the colonic microbiome induced by FMT via each route changes in the metabolome [short-chain fatty acids (SCFAs)] induced by FMT via each route effect of diet (donors) time from stool donation to treatment. Methods In this prospective, multicentre, open-label, parallel group, randomised pilot study, adult patients with mild to moderate active UC (partial Mayo score of ≥4 and ≤8) were recruited from three centres in the UK (Birmingham, Glasgow and St Mark’s, London). Patients were randomised to receive FMT delivered either via a NG tube for delivery to the stomach (foregut-NG) on 4 consecutive days repeated after a month or by a combination of delivery through a colonoscope followed by 7 weekly enemas (hindgut-COLON). All participants underwent a treatment schedule using FMT derived, in each case, from a single donor. The primary outcome was a composite assessment of both qualitative and quantitative data based on efficacy, acceptability and safety. Clinical response (primary measure of efficacy) was defined as a ≥3 point and a ≥30% reduction in full Mayo score from randomisation to week 8 and a ≥1 point reduction in the rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1. Patient and clinician acceptability of FMT and preference of treatment route was assessed through semi-structured qualitative research interviews. Interviews also explored reasons for adherence to treatment allocation and patients’ perspectives on FMT and trial experience. Participants were interviewed face to face or by telephone at two time points, first following the screening visit and prior to randomisation, and second after the 12-week follow-up period. Safety was assessed by the number of participants experiencing adverse events (AEs) and serious adverse events (SAEs). For the translational research, stool samples were taken from participants at baseline and then at 2 weekly intervals throughout the study to assess microbiome diversity (by 16S rRNA sequencing) and to examine the effect of FMT on faecal calprotectin. Donor stool samples were also analysed by 16S rRNA sequencing. Biopsy samples were taken from the colon at the time of endoscopy (baseline and week 8) to analyse mucosa-associated microbiome by 16S rRNA sequencing. SCFA levels in stool samples were also measured throughout the study and blood was taken from participants to look for changes in C-reactive protein (CRP) in response to FMT. Donors were asked to fill in a dietary questionnaire in order to look for associations between dietary components in their habitual diet and the efficacy of their donated FMT samples. Results Thirty patients with UC were randomised between March 2018 and April 2019; 16 to NG; 14 to COLON route. Seven participants in the NG arm and two participants in the colonic arm withdrew from the study. Clinical response was achieved in a higher proportion of participants in the colonic arm [9/12 (75%)] compared with the NG arm [2/8 (25%)]; [adjusted risk ratio 2.94 (95% confidence interval, 0.84 to 10.30)]. In the colonic arm, 12/14 (86%) participants were considered adherent compared with 8/16 (50%) in the NG arm. AEs were reported in 11/14 (79%) participants in the colonic arm and 11/16 (69%) in the NG arm. There were three SAEs in two participants in the NG arm, and none in the colonic arm. Qualitative research found a high level of enthusiasm for the trial among both patients and staff. Patients were more positive about the colonic treatment route than the NG route, both before randomisation and after the patients had been through the study. Lower calprotectin levels, implying reduced colonic inflammation, averaged over the last half of the treatment course (weeks 4, 6 and 8), were seen in the responders (N = 11, mean 508.6 mg/kg) versus the non-responders (N = 9, mean 853.6 mg/kg) (p = 0.03). Furthermore, there was a negative association between faecal microbiome alpha diversity [rarefied total operational taxonomic unit (OTU) richness] and calprotectin levels (p < 0.01). This is the first time that change in faecal calprotectin, a widely used clinical inflammatory biomarker in UC, has been reported in response to FMT in inflammatory bowel disease (IBD). With respect to SCFAs, there were significant and large increases observed in the concentration of acetate (45% increase, p = 0.05) and butyrate (57% increase, p = 0.03) across all participants (N = 19) from baseline to week 2 following FMT treatment. This effect was also observed over the course of the entire FMT treatment period from baseline to 8 weeks (N = 16, acetate 21% increase, p = 0.02; butyrate 39% increase, p = 0.08). Significant changes were not observed for the other SCFAs measured, notably propionate (2 weeks p = 0.46, 8 weeks p = 0.36). The observed increase in acetate and butyrate was not associated with clinical response, and in fact when restricted to the responder group (N = 9) changes at both 2 and 8 weeks were no longer significant, although increases were still observed. Across all participants that completed FMT to day 56, and for whom baseline and week 8 DNA was available (N = 13), there was no significant change in faecal microbiome alpha diversity, as measured by rarefied Shannon diversity of 3% OTUs (p = 0.43). However, when restricted to the colonic arm only (N = 8), there was a significant increase in alpha diversity (p = 0.01) observed after FMT. Again, for those participants in the colonic arm that responded to FMT, there was a significant increase in alpha diversity (rarefied Shannon diversity, p < 0.01) compared to those who did not. No differences were seen in alpha diversity of mucosa-associated bacteria pre and post treatment. Donor microbiome diversity, as measured by rarefied 16S rRNA gene Shannon diversity, varied substantially between donors. There was a non-significant positive association between clinical response and donor diversity (p = 0.19) with the treatment arm taken into account. In this pilot study, CRP values were lower at baseline in the colonic arm (4.2 mg/l) compared with the NG arm (11.3 mg/l). Similarly, CRP values at weeks 4, 6 and 8 were also lower in the colonic arm than in the NG arm. With regard to data derived from diet questionnaires administered to donors, higher milk and milk product intakes were associated with higher alpha diversity, but this was not statistically significant. The mean number of days from stool donation to FMT treatment was similar in participants who achieved a clinical response compared with those who did not achieve a clinical response. There was no association between time from stool donation and treatment, and clinical response when added to the primary intention-to-treat analysis model. Conclusion This pilot study suggests that in patients with active UC, FMT delivered via the colonic route appears to be safe and better tolerated with signals suggesting greater efficacy compared to the NG route. The pilot study was welcomed by patients and clinicians, and FMT appears, at least in the short term, to be safe and well tolerated. On review of these data, the Independent Oversight Committee recommended progressing to the planned placebo-controlled randomised trial, which would be powered to assess efficacy, and would have enabled more detailed mechanistic studies to assess for strains engrafting from donors to recipients, which are associated with clinical response. Patients remain very interested in FMT as a potential treatment for UC as this microbiome manipulation affords an alternative therapy to immune system suppression as a means to treat UC. The trial management group involved in this pilot believe that further studies to assess the efficacy of FMT in UC with a focus on understanding mechanisms are warranted as the first step towards developing precision live biotherapeutics for IBD. Trial registration This trial is registered as ISRCTN74072945 and EudraCT 2015-005753-12. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 13/179/01) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 14. See the NIHR Funding and Awards website for further award information.

Biodiversity genomics research requires reliable organismal identification, which can be difficult based on morphology alone. DNA-based identification using DNA barcoding can provide confirmation of species identity and resolve taxonomic issues but is rarely used in studies generating reference genomes. Here, we describe the development and implementation of DNA barcoding for the Darwin Tree of Life Project (DToL), which aims to sequence and assemble high quality reference genomes for all eukaryotic species in Britain and Ireland. We present a standardised framework for DNA barcode sequencing and data interpretation that is then adapted for diverse organismal groups. DNA barcoding data from over 12,000 DToL specimens has identified up to 20% of samples requiring additional verification, with 2% of seed plants and 3.5% of animal specimens subsequently having their names changed. We also make recommendations for future developments using new sequencing approaches and streamlined bioinformatic approaches.

Abstract The charge density wave material 1T-TaS2 exhibits a pulse-induced insulator-to-metal transition, which shows promise for next-generation electronics such as memristive memory and neuromorphic hardware. However, the rational design of TaS2 devices is hindered by a poor understanding of the switching mechanism, the pulse-induced phase, and the influence of material defects. Here, we operate a 2-terminal TaS2 device within a scanning transmission electron microscope at cryogenic temperature, and directly visualize the changing charge density wave structure with nanoscale spatial resolution and down to 300 μs temporal resolution. We show that the pulse-induced transition is driven by Joule heating, and that the pulse-induced state corresponds to the nearly commensurate and incommensurate charge density wave phases, depending on the applied voltage amplitude. With our in operando cryogenic electron microscopy experiments, we directly correlate the charge density wave structure with the device resistance, and show that dislocations significantly impact device performance. This work resolves fundamental questions of resistive switching in TaS2 devices, critical for engineering reliable and scalable TaS2 electronics.

Little attention has been devoted to understanding the language surrounding e-cigarette use. Researchers employ terms such as users of e-cigarettes or ENDS, but language employed outside scholarly writing is relatively unexamined. Thus, this study examined the language used by college students to refer to people who use e-cigarettes. College students (N = 1037; Mage= 20.67, SD = 3.81; 72.1% female; 69.6% White) at a southern U.S. university responded to the open-ended question: “What do you call a person who uses e-cigarettes?” Of 1086 responses, e-cigarette users’ (n = 591) and nonusers’ (n = 495) responses were examined separately. Although users and nonusers had the same two top terms (“vaper” and “smoker”), a clearer consensus existed among users where “vaper” was most common (51.3%) followed by “smoker” (21.0%). These same terms were endorsed by 37.0% and 31.5% of nonusers, respectively. The third most popular responses of users related to addiction (e.g., “addict”, “fiend”; 8.46%), whereas nonusers’ responses indicated they did not know what to call an e-cigarette user (e.g., “I don’t know”; 7.1%). Users were equally likely to use positive (e.g., “Vape God”) and negative (e.g., “fool”) terms, whereas nonusers were nearly six times more likely to use negative terms. Therefore, it may be useful to capitalize on these language trends in health campaigns as well as develop separate messaging for users vs. nonusers.

Abstract Background Limited evidence exists on how temperature increases are associated with hospital visits from alcohol- and substance-related disorders, despite plausible behavioral and physiological pathways. Methods In the present study, we implemented a case-crossover design, which controls for seasonal patterns, long-term trends, and non- or slowly-varying confounders, with distributed lag non-linear temperature terms (0–6 days) to estimate associations between daily ZIP Code-level temperature and alcohol- and substance-related disorder hospital visit rates in New York State during 1995–2014. We also examined four substance-related disorder sub-causes (cannabis, cocaine, opioid, sedatives). Results Here we show that, for alcohol-related disorders, a daily increase in temperature from the daily minimum (−30.1 °C (−22.2 °F)) to the 75th percentile (18.8 °C (65.8 °F)) across 0–6 lag days is associated with a cumulative 24.6% (95%CI,14.6%–34.6%) increase in hospital visit rates, largely driven by increases on the day of and day before hospital visit, with an association larger outside New York City. For substance-related disorders, we find evidence of a positive association at temperatures from the daily minimum (−30.1 °C (−22.2 °F)) to the 50th percentile (10.4 °C (50.7 °F)) (37.7% (95%CI,27.2%–48.2%), but not at higher temperatures. Findings are consistent across age group, sex, and social vulnerability. Conclusions Our work highlights how hospital visits from alcohol- and substance-related disorders are currently impacted by elevated temperatures and could be further affected by rising temperatures resulting from climate change. Enhanced social infrastructure and health system interventions could mitigate these impacts.

Introduction Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient’s quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments.Methods and analysis This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures.Ethics and dissemination Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk.Trial registration number ISRCTN96296121.

Spaying female and castrating male dogs, hereinafter referred to as neutering, is a US convention for the first year in the dog's life. Research on 35 breeds of dogs revealed that early neutering increases risks of joint disorders, such as hip dysplasia (HD), elbow dysplasia (ED), or cranial cruciate ligament (CCL) tear, or cancers, such as lymphosarcoma (LSA), mast cell tumor (MCT), hemangiosarcoma (has), or osteosarcoma (OSA), for some breeds. Joint disorder risks are heightened for some larger breeds and for mixed-breed dogs weighing more than 20 kg. Some breeds had elevated risks for cancers. Several other research teams have reported health complications associated with neutering. The study goal includes using the same methodology for data collection and analyses as in the study on 35 breeds for five additional dog breeds weighing at least 20 kg. The breeds were: German Short/Wirehaired Pointer, Mastiff, Newfoundland, Rhodesian Ridgeback, and Siberian Husky. Major differences among breeds appeared in vulnerability to joint disorders and cancers with early neutering: male and female Pointer breeds had elevated joint disorders and increased cancers; male Mastiff breeds had increased CCL and LSA and females had non-significant elevated CCL risks; female Newfoundland breeds had heightened risks for joint disorders and males had non-significant elevated risks; female Ridgeback breeds had heightened MCT with very early neutering; and Siberian Huskies showed no significant effects on joint disorders or cancers, but female breeds showed a non-significant but elevated CCL. Updated guidelines cover 40 dog breeds. These results further emphasize the importance of personalized decisions regarding the neutering of dogs, considering the dog's breed, sex, and context.

We present a genome assembly from an individual specimen of Luzula sylvatica (great wood-rush; Tracheophyta; Magnoliopsida; Poales; Juncaceae). The genome sequence is 444.5 megabases in span. Most of the assembly is scaffolded into 6 chromosomal pseudomolecules. The mitochondrial and plastid genome assemblies have lengths of 633.36 kilobases and 201.32 kilobases in length, respectively.

Abstract The layer stacking order in 2D materials strongly affects functional properties and holds promise for next-generation electronic devices. In bulk, octahedral MoTe2 possesses two stacking arrangements, the ferroelectric Weyl semimetal Td phase and the higher-order topological insulator 1T′ phase. However, in thin flakes of MoTe2, it is unclear if the layer stacking follows the Td, 1T′, or an alternative stacking sequence. Here, we use atomic-resolution scanning transmission electron microscopy to directly visualize the MoTe2 layer stacking. In thin flakes, we observe highly disordered stacking, with nanoscale 1T′ and Td domains, as well as alternative stacking arrangements not found in the bulk. We attribute these findings to intrinsic confinement effects on the MoTe2 stacking-dependent free energy. Our results are important for the understanding of exotic physics displayed in MoTe2 flakes. More broadly, this work suggests c-axis confinement as a method to influence layer stacking in other 2D materials.

IntroductionThe last decade has led to rapid developments and increased usage of computational tools at the single-cell level. However, our knowledge remains limited in how extracellular cues alter quantitative macrophage morphology and how such morphological changes can be used to predict macrophage phenotype as well as cytokine content at the single-cell level.MethodsUsing an artificial intelligence (AI) based approach, this study determined whether (i) accurate macrophage classification and (ii) prediction of intracellular IL-10 at the single-cell level was possible, using only morphological features as predictors for AI. Using a quantitative panel of shape descriptors, our study assessed image-based original and synthetic single-cell data in two different datasets in which CD14+ monocyte-derived macrophages generated from human peripheral blood monocytes were initially primed with GM-CSF or M-CSF followed by polarization with specific stimuli in the presence/absence of continuous GM-CSF or M-CSF. Specifically, M0, M1 (GM-CSF-M1, TNFα/IFNγ-M1, GM-CSF/TNFα/IFNγ-M1) and M2 (M-CSF-M2, IL-4-M2a, M-CSF/IL-4-M2a, IL-10-M2c, M-CSF/IL-10-M2c) macrophages were examined.ResultsPhenotypes were confirmed by ELISA and immunostaining of CD markers. Variations of polarization techniques significantly changed multiple macrophage morphological features, demonstrating that macrophage morphology is a highly sensitive, dynamic marker of phenotype. Using original and synthetic single-cell data, cell morphology alone yielded an accuracy of 93% for the classification of 6 different human macrophage phenotypes (with continuous GM-CSF or M-CSF). A similarly high phenotype classification accuracy of 95% was reached with data generated with different stimuli (discontinuous GM-CSF or M-CSF) and measured at a different time point. These comparably high accuracies clearly validated the here chosen AI-based approach. Quantitative morphology also allowed prediction of intracellular IL-10 with 95% accuracy using only original data.DiscussionThus, image-based machine learning using morphology-based features not only (i) classified M0, M1 and M2 macrophages but also (ii) classified M2a and M2c subtypes and (iii) predicted intracellular IL-10 at the single-cell level among six phenotypes. This simple approach can be used as a general strategy not only for macrophage phenotyping but also for prediction of IL-10 content of any IL-10 producing cell, which can help improve our understanding of cytokine biology at the single-cell level.

Abstract Background PacBio HiFi sequencing provides highly accurate long-read sequencing datasets which are of great advantage for whole genome sequencing projects. One limitation of the method is the requirement for high quality, high molecular weight input DNA. This can be particularly challenging for plants that frequently contain common and species-specific secondary metabolites, which often interfere with downstream processes. Cape Primroses (genus Streptocarpus), are some of these recalcitrant plants and are selected here as material to develop a high quality, high molecular weight DNA extraction protocol for long read genome sequencing. Results We developed a DNA extraction method for PacBio HiFi sequencing for Streptocarpus grandis and Streptocarpus kentaniensis. A CTAB lysis buffer was employed to avoid guanidine, and the traditional chloroform and phenol purification steps were replaced with pre-lysis sample washes. Best cells/nucleus lysis was achieved with 4 h at 58 °C. The obtained high quality and high molecular weight DNAs were tested in PacBio SMRTBell™ library preparations, which resulted in circular consensus sequencing (CCS) reads from 17 to 27 Gb per cell, and a read length N50 from 14 to 17 kbp. To evaluate the quality of the reads for whole genome sequencing, they were assembled with HiFiasm into draft genomes, with N50 = 49 Mb and 23 Mb, and L50 = 10 and 11. The longest contigs were 95 Mb and 57 Mb respectively, showing good contiguity as these are longer than the theoretical chromosome length (genome size/chromosome number) of 78 Mb and 55 Mb, for S. grandis and S. kentaniensis respectively. Conclusions DNA extraction is a critical step towards obtaining a complete genome assembly. Our DNA extraction method here provided the required high quality, high molecular weight DNA for successful standard-input PacBio HiFi library preparation. The contigs from those reads showed a high contiguity, providing a good starting draft assembly towards obtaining a complete genome. The results obtained here were highly promising, and demonstrated that the DNA extraction method developed here is compatible with PacBio HiFi sequencing and suitable for de novo whole genome sequencing projects of plants.

OBJECTIVES:. To evaluate the association of race with proportion of time in deep sedation among mechanically ventilated adults. DESIGN:. Retrospective cohort study from October 2017 to December 2019. SETTING:. Five hospitals within a single health system. PATIENTS:. Adult patients who identified race as Black or White who were mechanically ventilated for greater than or equal to 24 hours in one of 12 medical, surgical, cardiovascular, cardiothoracic, or mixed ICUs. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The exposure was White compared with Black race. The primary outcome was the proportion of time in deep sedation during the first 48 hours of mechanical ventilation, defined as Richmond Agitation-Sedation Scale values of –3 to –5. For the primary analysis, we performed mixed-effects linear regression models including ICU as a random effect, and adjusting for age, sex, English as preferred language, body mass index, Elixhauser comorbidity index, Laboratory-based Acute Physiology Score, Version 2, ICU admission source, admission for a major surgical procedure, and the presence of septic shock. Of the 3337 included patients, 1242 (37%) identified as Black, 1367 (41%) were female, and 1002 (30%) were admitted to a medical ICU. Black patients spent 48% of the first 48 hours of mechanical ventilation in deep sedation, compared with 43% among White patients in unadjusted analysis. After risk adjustment, Black race was significantly associated with more time in early deep sedation (mean difference, 5%; 95% CI, 2–7%; p < 0.01). CONCLUSIONS:. There are disparities in sedation during the first 48 hours of mechanical ventilation between Black and White patients across a diverse set of ICUs. Future work is needed to determine the clinical significance of these findings, given the known poorer outcomes for patients who experience early deep sedation.

Introduction Associations between exposure to nature and positive mental health outcomes have been established. Although the Internet is a popular source of accessing mental health information, little is known about the readability of such online information. Thus, the goal of this study was to assess the readability of online information regarding the association between exposure to nature and mental health. Methods A search of webpages was conducted using the following search terms: ‘mental health and urban greening’, ‘stress and urban greening’, ‘mental health and nature’, ‘stress and nature’, ‘mental health and outdoors’, and ‘stress and outdoors’. Readability of the 255 webpages identified was determined by the Flesch-Kincaid Grade Level measure. Results On average, webpage content was written at an 11th grade reading level (Flesch-Kincaid Grade Level mean=11.95, SD=2.68), and fewer than 2% of webpages met readability guidelines (i.e. ≤6th grade reading level). Conclusions Most online content related to nature and mental health should be written at a more appropriate level for general audiences. Web content developers should prioritize adherence to readability guidelines.

Abstract Recent technological advances in long‐read high‐throughput sequencing and assembly methods have facilitated the generation of annotated chromosome‐scale whole‐genome sequence data for evolutionary studies; however, generating such data can still be difficult for many plant species. For example, obtaining high‐molecular‐weight DNA is typically impossible for samples in historical herbarium collections, which often have degraded DNA. The need to fast‐freeze newly collected living samples to conserve high‐quality DNA can be complicated when plants are only found in remote areas. Therefore, short‐read reduced‐genome representations, such as target capture and genome skimming, remain important for evolutionary studies. Here, we review the pros and cons of each technique for non‐model plant taxa. We provide guidance related to logistics, budget, the genomic resources previously available for the target clade, and the nature of the study. Furthermore, we assess the available bioinformatic analyses, detailing best practices and pitfalls, and suggest pathways to combine newly generated data with legacy data. Finally, we explore the possible downstream analyses allowed by the type of data generated using each technique. We provide a practical guide to help researchers make the best‐informed choice regarding reduced genome representation for evolutionary studies of non‐model plants in cases where whole‐genome sequencing remains impractical.

Associations between neighborhood greenness and socioeconomic status (SES) are established, yet intra-neighborhood context and SES-related barriers to tree planting remain unclear. Large-scale tree planting implementation efforts are increasingly common and can improve human health, strengthen climate adaptation, and ameliorate environmental inequities. Yet, these efforts may be ineffective without in-depth understanding of local SES inequities and barriers to residential planting.We recruited 636 residents within and surrounding the Oakdale Neighborhood of Louisville, Kentucky, USA, and evaluated associations of individual and neighborhood-level sociodemographic indicators with greenness levels at multiple scales. We offered no-cost residential tree planting and maintenance to residents within a subsection of the neighborhood and examined associations of these sociodemographic indicators plus baseline greenness levels with tree planting adoption among 215 eligible participants.We observed positive associations of income with Normalized Difference Vegetation Index (NDVI) and leaf area index (LAI) within all radii around homes, and within yards of residents, that varied in strength. There were stronger associations of income with NDVI in front yards but LAI in back yards. Among Participants of Color, associations between income and NDVI were stronger than with Whites and exhibited no association with LAI. Tree planting uptake was not associated with income, education, race, nor employment status, but was positively associated with lot size, home value, lower population density, and area greenness.Our findings reveal significant complexity of intra-neighborhood associations between SES and greenness that could help shape future research and equitable greening implementation. Results show that previously documented links between SES and greenspace at large scales extend to residents’ yards, highlighting opportunities to redress greenness inequities on private property. Our analysis found that uptake of no-cost residential planting and maintenance was nearly equal across SES groups but did not redress greenness inequity. To inform equitable greening, further research is needed to evaluate culture, norms, perceptions, and values affecting tree planting acceptance among low-SES residents.

Significance: Determining if tobacco-related biomarkers of exposure (BOE) are associated with respiratory symptoms is an important public health tool that can be used to evaluate the potential harm of different tobacco products. Methods: Adult data from people who exclusively smoked cigarettes (N = 2,438) in Waves 1–4 (2013–2017) of the Population Assessment of Tobacco and Health Study were stacked to examine associations between baseline and follow-up within wave pairs (W1-W2, W2-W3, W3-W4). Weighted generalized estimating equation models were used to evaluate associations between biomarkers of nicotine, tobacco-specific nitrosamines, acrolein, acrylonitrile, cadmium, and lead at baseline/follow-up and respiratory symptom(s) (wheezing/whistling in the chest, wheezing during exercise, and/or dry cough in the past 12 months) at follow-up. Results: Higher acrolein metabolite (CEMA) levels at follow-up were associated with increased odds of respiratory symptoms at follow-up for people who exclusively smoked cigarettes (aOR = 1.34; 95% CI = 1.06, 1.70), including when limited to those without a diagnosed respiratory disease (aOR = 1.46; 95% CI = 1.12, 1.90) and those who smoked daily (aOR = 1.40; 95% CI = 1.06, 1.84). Higher cadmium levels at baseline (while controlling for follow-up levels) were associated with reduced odds of respiratory symptoms at follow-up (aOR = 0.80; 95% CI = 0.65, 0.98) among people who exclusively smoked cigarettes without a respiratory disease. There were no significant associations between baseline/follow-up BOE and follow-up respiratory symptoms for people who smoked cigarettes non-daily. Conclusions: This research supports measuring biomarkers of acrolein, such as CEMA, as a potential intermediate measurement for increased respiratory symptom development. Measuring these biomarkers could help alleviate the clinical burden of respiratory disease.

Introduction Given the growing awareness of the health risks associated with e-cigarettes, many users will access information about how to effectively quit using e-cigarettes, and the internet likely will be a popular source of information. However, little is known about the readability of online e-cigarette cessation information. Therefore, the goal of the current study was to assess the readability of webpage information about e-cigarette cessation. Methods A search of webpages was conducted using the following search terms: vaping addiction, quit vaping, quit Juul, stop vaping, stop Juul, and vaping cessation. The 464 webpages identified were coded for target audience, message valence, and source, and then assessed for reading level with the Flesch-Kincaid Grade Level assessment. Results On average, webpage content was written at a 7th grade reading level (Flesch-Kincaid Grade Level Mean=7.34, SD=2.22) and less than 25% of webpages met readability guidelines (i.e. ≤6th grade reading level). There were no differences in readability by target audience, message valence, or webpage source. Conclusions The results suggest that most online content related to e-cigarette cessation is not written at a level that is easily understood by general audiences. Thus, tobacco control advocates should assess the reading level of their messaging to ensure wide accessibility of information.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Abstract Synthesis of transition metal dichalcogenides (TMDCs) has been achieved through the direct conversion of metal and metal‐oxide films, demonstrating the ability to grow large area thin films with uniform thickness on a variety of substrates and direct control over the growth orientation (horizontal vs vertical) of the TMDC layers. However, the synthesized TMDC films often exhibit small grains and are more defective than their bulk counterparts. This is especially true for 2D telluride films due to the low reactivity between tellurium and transition metals such as W and Mo. In this work, the substrate interactions is examined for WTe2 converted from amorphous WOx thin films grown by atomic layer deposition, on c‐plane sapphire and SiO2 through tellurization at high temperatures. Similar to TMDC telluride MoTe2, the formation of monolayer WTe2 on sapphire is observed, but not on SiO2. However, due to decreased diffusion of W on sapphire compared to Mo, the formation of WTe2 flakes instead of continuous films is observed, providing insight into the role of the specific transition metal during the direct synthesis of TMDC telluride films.

The oxidative tricarboxylic acid (TCA) cycle is a central mitochondrial pathway integrating catabolic conversions of NAD +to NADH and anabolic production of aspartate, a key amino acid for cell proliferation. Several TCA cycle components are implicated in tumorigenesis, including loss-of-function mutations in subunits of succinate dehydrogenase (SDH), also known as complex II of the electron transport chain (ETC), but mechanistic understanding of how proliferating cells tolerate the metabolic defects of SDH loss is still lacking. Here, we identify that SDH supports human cell proliferation through aspartate synthesis but, unlike other ETC impairments, the effects of SDH inhibition are not ameliorated by electron acceptor supplementation. Interestingly, we find aspartate production and cell proliferation are restored to SDH-impaired cells by concomitant inhibition of ETC complex I (CI). We determine that the benefits of CI inhibition in this context depend on decreasing mitochondrial NAD+/NADH, which drives SDH-independent aspartate production through pyruvate carboxylation and reductive carboxylation of glutamine. We also find that genetic loss or restoration of SDH selects for cells with concordant CI activity, establishing distinct modalities of mitochondrial metabolism for maintaining aspartate synthesis. These data therefore identify a metabolically beneficial mechanism for CI loss in proliferating cells and reveal how compartmentalized redox changes can impact cellular fitness.

Abstract The gut microbiota (GM) exerts a strong influence over the host immune system and dysbiosis of this microbial community can affect the clinical phenotype in chronic inflammatory conditions. To explore the role of the GM in lupus nephritis, we colonized NZM2410 mice with Segmented Filamentous Bacteria (SFB). Gut colonization with SFB was associated with worsening glomerulonephritis, glomerular and tubular immune complex deposition and interstitial inflammation compared to NZM2410 mice free of SFB. With SFB colonization mice experienced an increase in small intestinal lamina propria Th17 cells and group 3 innate lymphoid cells (ILC3s). However, although serum IL-17A expression was elevated in these mice, Th17 cells and ILC3s were not detected in the inflammatory infiltrate in the kidney. In contrast, serum and kidney tissue expression of the macrophage chemoattractants MCP-1 and CXCL1 were significantly elevated in SFB colonized mice. Furthermore, kidney infiltrating F4/80+CD206+M2-like macrophages were significantly increased in these mice. Evidence of increased gut permeability or “leakiness” was also detected in SFB colonized mice. Finally, the intestinal microbiome of SFB colonized mice at 15 and 30 weeks of age exhibited dysbiosis when compared to uncolonized mice at the same time points. Both microbial relative abundance as well as biodiversity of colonized mice was found to be altered. Collectively, SFB gut colonization in the NZM2410 mouse exacerbates kidney disease, promotes kidney M2-like macrophage infiltration and overall intestinal microbiota dysbiosis.

IntroductionLittle is known how inflammatory processes quantitatively affect chondrocyte morphology and how single cell morphometric data could be used as a biological fingerprint of phenotype.MethodsWe investigated whether trainable high-throughput quantitative single cell morphology profiling combined with population-based gene expression analysis can be used to identify biological fingerprints that are discriminatory of control vs. inflammatory phenotypes. The shape of a large number of chondrocytes isolated from bovine healthy and human osteoarthritic (OA) cartilages was quantified under control and inflammatory (IL-1β) conditions using a trainable image analysis technique measuring a panel of cell shape descriptors (area, length, width, circularity, aspect ratio, roundness, solidity). The expression profiles of phenotypically relevant markers were quantified by ddPCR. Statistical analysis, multivariate data exploration, and projection-based modelling were used for identifying specific morphological fingerprints indicative of phenotype.ResultsCell morphology was sensitive to both cell density and IL-1β. In both cell types, all shape descriptors correlated with expression of extracellular matrix (ECM)- and inflammatory-regulating genes. A hierarchical clustered image map revealed that individual samples sometimes responded differently in control or IL-1β conditions than the overall population. Despite these variances, discriminative projection-based modeling revealed distinct morphological fingerprints that discriminated between control and inflammatory chondrocyte phenotypes: the most essential morphological characteristics attributable to non-treated control cells was a higher cell aspect ratio in healthy bovine chondrocytes and roundness in OA human chondrocytes. In contrast, a higher circularity and width in healthy bovine chondrocytes and length and area in OA human chondrocytes indicated an inflammatory (IL-1β) phenotype. When comparing the two species/health conditions, bovine healthy and human OA chondrocytes exhibited comparable IL-1β-induced morphologies in roundness, a widely recognized marker of chondrocyte phenotype, and aspect ratio.DiscussionOverall, cell morphology can be used as a biological fingerprint for describing chondrocyte phenotype. Quantitative single cell morphometry in conjunction with advanced methods for multivariate data analysis allows identifying morphological fingerprints that can discriminate between control and inflammatory chondrocyte phenotypes. This approach could be used to assess how culture conditions, inflammatory mediators, and therapeutic modulators regulate cell phenotype and function.

Background Familial cerebral cavernous alformation (CCM) is an autosomal dominant disease caused by mutations in KRIT1, CCM2, or PDCD10. Cases typically present with multiple lesions, strong family history, and neurological symptoms, including seizures, headaches, or other deficits. Intracranial hemorrhage (ICH) is a severe manifestation of CCM, which can lead to death or long‐term neurological deficits. Few studies have reported ICH rates and risk factors in familial CCM. We report ICH rates and assess whether CCM lesion burden, a disease severity marker, is associated with risk of symptomatic ICH during follow‐up in a well‐characterized cohort of familial CCM cases. Methods and Results We studied 386 patients with familial CCM with follow‐up data enrolled in the Brain Vascular Malformation Consortium CCM Project. We estimated symptomatic ICH rates overall and stratified by history of ICH before enrollment. CCM lesion burden (total lesion count and large lesion size) assessed at baseline enrollment was tested for association with increased risk of subsequent ICH during follow‐up using Cox regression models adjusted for history of ICH before enrollment, age, sex, and family structure and stratified on recruitment site. The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient‐years (95% CI, 1.9–4.1). Those with ICH before enrollment had a follow‐up ICH rate of 4.5 per 100 patient‐years (95% CI, 2.6–8.1) compared with 2.0 per 100 patient‐years (95% CI, 1.3–3.5) in those without (P=0.042). Total lesion count was associated with increased risk of ICH during follow‐up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10–1.71], P=0.006). The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient‐years (95% CI, 1.9–4.1). Those with ICH before enrollment had a follow‐up ICH rate of 4.5 per 100 patient‐years (95% CI, 2.6–8.1) compared with 2.0 per 100 patient‐years (95% CI, 1.3–3.5) in those without (P=0.042). Total lesion count was associated with increased risk of ICH during follow‐up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10–1.71], P=0.006). Conclusions Patients with familial CCM with prior history of an ICH event are at higher risk for rehemorrhage during follow‐up. In addition, total CCM lesion burden is significantly associated with increased risk of subsequent symptomatic ICH; hence lesion burden may be an important predictor of patient outcome and aid patient risk stratification.

In recent years, there has been a shift in the literature towards identifying how ongoing stress adversely affects mental health beyond the effect of direct exposure to war-related violence. The goal of the current study was to investigate the relationship between displacement-related stressors and trauma symptom severity. Participants (N ​= ​1015) were recruited from primary healthcare clinics (PHCs) in Northern Sri Lanka and completed a demographic and displacement history questionnaire, the Stressful Life Events Checklist, and the Harvard Trauma Questionnaire. Four latent stressor constructs were identified through exploratory and confirmatory factor analyses: 1) personal safety concerns; 2) war-related loss; 3) material loss, and 4) personal hardships. Structural equation modeling was used to examine the relationship between stressors and trauma symptom severity. In the final structural equation model, war-related loss and material loss were positively related to symptom severity whereas psychosocial hardship was found to be negatively related to symptom severity. Results highlight how an integrated model of mental health can more fully inform the needs stemming from displacement-related stressors.