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A major challenge for universities across the globe is to address the lack of diversity within higher education. Widening participation (WP) programmes can vary between in-reach and outreach programmes. Some initiatives focus on either pre-entry stage (primary or secondary schools) or post-entry stage (helping students adapt to university life). This systematic literature review provides an analysis of the effectiveness of widening participation outreach programmes, a topic that is relatively unexplored, particularly at school level education. By examining empirical studies of widening participation interventions, the paper allows for the investigation of the educational outcomes measured in these programmes. A total of 19 studies were included, which analysed quantitative or mixed-method data. The findings indicate a growth in the evidence base for widening participation programmes for second-level students over the last decade. Interventions identified in the literature were categorised by their approach, which included guidance-based interventions, multidimensional interventions or pedagogical interventions. The findings confirm some positive effects for widening participation outreach programmes on a range of outcomes including students' college readiness, educational aspirations and college enrolment. The review argues for consistency in the way in which educational outcomes are measured, as well as the need for cross-collaboration and sharing of data between schools and universities, to enable more effective measurement of widening participation programmes in future research.

We assessed different aspects of tactile perception in young children (3-6 years) with autism. Autistic and neurotypical children completed vibrotactile tasks assessing reaction time, amplitude discrimination (sequential and simultaneous) and temporal discrimination (temporal order judgment and duration discrimination). Autistic children had elevated and more variable reaction times, suggesting slower perceptual-motor processing speed and/or greater distractibility. Children with autism also showed higher amplitude discrimination and temporal order judgement thresholds compared to neurotypical children. Tactile perceptual metrics did not associate with social or tactile sensitivities measured by parent-reports. Altered tactile behavioral responses appear in early childhood, can be quantified but appear dissociated from sensitivity. This implies these measures are complementary, but not necessarily related, phenomena of atypical tactile perception in autism.

Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease caused by COVID-19. An orally bioavailable RDV analog may facilitate earlier treatment of non-hospitalized COVID-19 patients. Here we describe the synthesis and evaluation of alkyl glyceryl ether phosphodiesters of GS-441524 (RVn), lysophospholipid analogs which allow for oral bioavailability and stability in plasma. Oral treatment of SARS-CoV-2-infected BALB/c mice with 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-RVn (60 mg/kg orally, once daily for 5 days starting 12h after infection) reduced lung viral load by 1.5 log10 units versus vehicle at day 2 and to below the limit of detection at day 5. Structure/activity evaluation of additional analogs that have hydrophobic ethers at the sn-2 of glycerol revealed improved in vitro antiviral activity by introduction of a 3-fluoro-4-methoxy-substituted benzyl or a 3- or 4-cyano-substituted benzyl. Collectively, our data support the development of RVn phospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections.

The factors contributing to the rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.4 and BA.5 subvariants in populations that experienced recent surges of BA.2 and BA.2.12.1 infections are not understood. Neutralizing antibodies (NAbs) are likely to protect against severe disease if present in sufficient quantity. We found that after BA.2 or BA.2.12.1 infection, NAb responses were largely cross-neutralizing but were much less effective against BA.5. In addition, individuals who were infected and treated early with nirmatrelvir/ritonavir (Paxlovid) had lower NAb levels than untreated individuals.

This study sought to investigate the effects of a self-monitoring (SM) with goal-setting (GS) intervention on students' disruptive behavior. A multiple baseline A-B-BC design was implemented across five elementary school-aged participants diagnosed with attention-deficit/hyperactivity disorder (ADHD) to examine the use of a behavioral intervention combining SM and GS techniques to decrease disruptive behavior. The results of this study suggest that SM with GS appears to be an effective intervention package for decreasing the disruptive behavior of students with ADHD and that these behavioral decreases sustain after intervention completion. Results also suggest moderate benefits of using a SM with GS intervention over a SM intervention. Teacher ratings suggest that the SM with GS package is moderately acceptable for classroom use.

Introduction: ALK-positive lung cancers represent a molecularly diverse disease. With drug exposure, driving selection pressure, and resistance pathways, disease relapse will emerge. There is compelling rationale to investigate novel treatment strategies, informed by dynamic circulating tumor DNA (ctDNA) monitoring. Methods: The single-arm, pilot study ALKTERNATE investigated fixed alternating cycles of lorlatinib intercalated with crizotinib in individuals resistant to second-generation ALK inhibitors. Dynamic ctDNA explored the correlation with disease response and disease recurrence and defined disease resistance. The primary outcome was time-to-treatment failure, a composite of tolerability, feasibility, and efficacy. Secondary outcomes included standard survival measures, toxicity, pharmacokinetic analysis, and patient-reported outcomes. Tertiary outcomes were proteogenomic analyses of tissue and plasma. Results: A total of 15 individuals were enrolled; three encountered primary resistance to lorlatinib induction. There were 12 participants who received alternating therapy, and this approach revealed safety, feasibility, and effectiveness. Patient-reported outcomes were maintained or improved on therapy, and toxicity was consistent with previous reports. The pharmacokinetic measures were similar to the single-arm drug experience. Median time-to-treatment failure was 10 months; overall survival was 23 months. ctDNA profiles indicated inferior survival in those with preexistent TP53 mutations and those without clear or cleared ctDNA at trial induction. The study defined a vastly heterogeneous population with an abundance of ALK coexisting with non-ALK resistance variants. Conclusions: ALKTERNATE revealed feasibility with a novel alternating ALK inhibitor strategy in ALK-positive NSCLC. Results support progressing inquiry into this approach and propose a flexible design with drug(s) selected and alternating time frames, informed by real-time plasma profiling. Moving this concept to treatment naive may also optimize impact.

Lesion studies have historically been instrumental for establishing causal connections between brain and behavior. They stand to provide additional insight if integrated with multielectrode techniques common in systems neuroscience. Here, we present and test a platform for creating electrolytic lesions through chronically implanted, intracortical multielectrode probes without compromising the ability to acquire neuroelectrophysiology. A custom-built current source provides stable current and allows for controlled, repeatable lesions in awake-behaving animals. Performance of this novel lesioning technique was validated using histology from ex vivo and in vivo testing, current and voltage traces from the device, and measurements of spiking activity before and after lesioning. This electrolytic lesioning method avoids disruptive procedures, provides millimeter precision over the extent and submillimeter precision over the location of the injury, and permits electrophysiological recording of single-unit activity from the remaining neuronal population after lesioning. This technique can be used in many areas of cortex, in several species, and theoretically with any multielectrode probe. The low-cost, external lesioning device can also easily be adopted into an existing electrophysiology recording setup. This technique is expected to enable future causal investigations of the recorded neuronal population’s role in neuronal circuit function, while simultaneously providing new insight into local reorganization after neuron loss.

Aim: To review and summarize existing literature and knowledge gaps regarding interventions that have been tested to optimize dispatcher-assisted CPR (DA-CPR) instruction protocols for out-of-hospital cardiac arrest (OHCA). Methods: This scoping review was undertaken by an International Liaison Committee on Resuscitation (ILCOR) Basic Life Support scoping review team and guided by the ILCOR methodological framework and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR). Studies were eligible for inclusion if they were published in peer-reviewed journals and evaluated interventions used to improve DA-CPR. The search was carried out in MEDLINE, EMBASE, Education Resources Information Center (ERIC), PsycINFO, the Cochrane Library, Evidence Based Medicine (EBM) Reviews, and the Campbell Library from 2000 to December 18, 2023. Results: After full text review, 31 studies were included in the final review. The interventions reviewed were use of video at the scene (n = 9), changes in terminology about compressions (n = 6), implementation of novel DA-CPR protocols (n = 4), advanced dispatcher training (n = 3), centralization of the dispatch center (n = 2), use of metronome or varied metronome rates (n = 2), change in CPR sequence and compression ratio (n = 1), animated audio-visual recording (n = 1), pre-recorded instructions vs. conversational live instructions (n = 1), inclusion of “undress patient” instructions (n = 1), and specific verbal encouragement (n = 1). Studies ranged in methodology from registry studies to randomized clinical trials with the majority being observational studies of simulated EMS calls for OHCA. Outcomes were highly variable but included rates of bystander CPR, confidence & willingness to perform CPR, time to initiation of bystander CPR, bystander CPR quality (including CPR metrics: chest compression depth and rate; chest compression fraction; full chest recoil, ventilation rate, overall CPR competency), rates of automated external defibrillator (AED) use, return of spontaneous circulation (ROSC) and survival. Overall, all interventions seem to be associated with potential improvement in bystander CPR and CPR metrics. Conclusion: There appears to be trends towards improvement on key outcomes however more research is needed. This scoping review highlights the lack of high-quality clinical research on any of the tested interventions to improve DA-CPR. There is insufficient evidence to explore the effectiveness of any of these interventions via systematic review.

Background: Previous systematic reviews have failed to find an association between the use of real-time feedback during cardiopulmonary resuscitation (CPR) and patient outcomes. However, these reviews excluded studies examining feedback with other system changes. As part of the International Liaison Committee on Resuscitation (ILCOR) continuous evidence evaluation process, we conducted a scoping review to examine the current state of this literature and the use of real-time feedback in this form. Methods/Data sources: A protocol and search strategy was developed. We searched Medline, EMBASE, and Allied Health Literature (CINAHL) from inception to May 2024. Cochrane (Cochrane (specifically, the Cochrane Database of Systematic Reviews) is contained in Medline so was not searched separately. Studies were eligible for inclusion if they were published or unpublished (grey-literature) studies involving children or adults that examined the effect of real-time feedback or prompting on the quality of CPR following cardiac arrest. Data were extracted and audited independently. For each study, the following information were extracted: the author(s); year of publication; timeframe; study design; country; population; intervention and comparator; type of feedback or prompt; outcomes measured; main findings for CPR quality, and; main findings for patient outcomes. Reviewers also allocated key themes to each study and held a series of consensus discussions to consolidate themes across the included studies. Results: We screened 2,657 titles and included 60 studies. Our analysis identified five overlapping themes in the extended literature: system change and quality improvement; impact on patient outcomes; better CPR quality without improved patient outcome; CPR feedback as a generator of other CPR metrics; and CPR feedback as a potential harm. Results revealed a substantial adjacent literature, particularly on implementing high-performance CPR as part of quality improvement programs. Conclusions: This scoping review has identified a large body of literature and specific themes of interest in relation to feedback for CPR quality. Future systematic reviews should include studies examining real-time feedback with other system changes.

Background: Ultraportable automated external defibrillators (AEDs) are a new generation of defibrillators that are small, lightweight, easy to carry on one’s person, and affordable for personal and home use. They offer the opportunity to increase AED availability in case of out-of-hospital cardiac arrest (OHCA) and therefore improve outcomes.We aimed to review evidence supporting the potential effect on outcomes and the performance of these ultraportable AEDs. Methods: We searched Ovid Medline, Embase and Cochrane databases from 2012 to July 4th, 2024 to identify any studies related to ultraportable AED. The population was adult and children with OHCA who were treated with an ultra-portable AED. All outcomes were accepted. We limited study designs to randomized controlled trials and non-randomized studies. Data charting was done by the primary author using standardized data abstraction forms. Results: The search strategy identified 54 studies (Pubmed = 26, Embase = 28, with 19 duplicates). We included three articles in the final review. One study was a medico-economic simulation study including 600,000 simulated patients, one is the study protocol of cluster randomized trial of providing ultraportable AEDs to first responders and one is an abstract with preliminary results of this trial reporting 1805 community responders recruited, 903 allocated to ultraportable AED. No studies to date have reported patient outcomes. Conclusion: This review found no evidence of ultraportable AED device performance, clinical or safety outcomes. There is an urgent need for further research to determine the safety and effectiveness of ultraportable AEDs.

Aim: To determine the effect of CPR delivery surface (e.g. firm mattress, floor, backboard) on patient outcomes and CPR delivery. Methods: We searched MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials for studies published since 2019 that evaluated the effect of CPR delivery surface in adults and children on patient outcomes and CPR depth (PROSPERO CRD42023467583). We included manikin studies due to a lack of human studies. We identified pre-2019 studies from the 2020 ILCOR evaluation of this topic. Two reviewers independently screened titles/abstracts and full-text papers, extracted data and assessed risk of bias. Evidence certainty for each outcome was evaluated using GRADE methodology. Where appropriate, we pooled data in a meta-analysis, using a random-effects model. Results: Database searches identified 489 citations. We included six studies published since 2019. We analysed these studies together with the eleven studies included in the previous ILCOR review. All included studies were manikin randomised controlled trials. Certainty of evidence was low. Interventions including placing the patient on the floor or the use of backboard had minimal impact on achieving greater compression depth. Meta-analyses of floor versus firm hospital mattress or firm home mattress found a mean difference of 5.36 mm (95% CI −1.59 to 12.32) and 2.11 mm (95% CI −3.23 to 7.45) respectively. Conclusion: The use of a backboard led to a small 2 mm increase in chest compression depth in meta-analysis of multiple mannikin trials. Use of a firm mattress or transitioning to the floor did not affect chest compression depth.

Background: The prefrontal cortex (PFC) has been strongly implicated in the pathophysiology of schizophrenia. Here, we combined high-resolution single-nuclei RNA sequencing data from the human PFC with large-scale genomic data for schizophrenia to identify constituent cell populations likely to mediate genetic liability to the disorder. Methods: Gene expression specificity values were calculated from a single-nuclei RNA sequencing dataset comprising 84 cell populations from the human PFC, spanning gestation to adulthood. Enrichment of schizophrenia common variant liability and burden of rare protein-truncating coding variants were tested in genes with high expression specificity for each cell type. We also explored schizophrenia common variant associations in relation to gene expression across the developmental trajectory of implicated neurons. Results: Common risk variation for schizophrenia was prominently enriched in genes with high expression specificity for a population of mature layer 4 glutamatergic neurons emerging in infancy. Common variant liability to schizophrenia increased along the developmental trajectory of this neuronal population. Fine-mapped genes at schizophrenia genome-wide association study risk loci had significantly higher expression specificity than other genes in these neurons and in a population of layer 5/6 glutamatergic neurons. People with schizophrenia had a higher rate of rare protein-truncating coding variants in genes expressed by cells of the PFC than control individuals, but no cell population was significantly enriched above this background rate. Conclusions: We identified a population of layer 4 glutamatergic PFC neurons likely to be particularly affected by common variant genetic risk for schizophrenia, which may contribute to disturbances in thalamocortical connectivity in the condition.

Background: In a previous study, we identified eight types of potential barriers to bystander cardiopulmonary resuscitation (CPR) initiation and continuation until the arrival of emergency medical services (EMS) on scene, in the context of emergency calls for out-of-hospital cardiac arrest (OHCA). Many cases had multiple barriers. In this study, we aimed to estimate the independent effects of these barriers after adjusting for case characteristics. Methods: We used data for the 295 non-trauma OHCAs from the St John Western Australian (SJ-WA) OHCA Database. Excluded cases were: EMS-witnessed OHCA, callers not with/close to the patient, OHCA not recognised during the emergency call, bystander CPR in progress prior to the call and calls coded as obvious death by SJ-WA. We conducted two multivariable logistic regression models including the eight barriers (callers: 1) perceived inappropriateness of CPR, 2) emotional distress, 3) reluctance to perform CPR, 4) physical limitations, 5) access to the patient, 6) leaving the scene, 7) communication failure, and 8) on-scene distractions) and case characteristics. Results: The callers perceiving CPR as inappropriate (adjusted odds ratio [AOR] = 0.20, 0.11–0.37) and witnessed arrest (AOR = 2.88, 95% CI 1.48–5.60) were independently associated with CPR initiation. Caller distractions such as performing other tasks or relaying information to other bystanders were negatively significantly associated with callers continuing CPR to EMS arrival (AOR = 0.27, 0.10–0.73). Conclusions: Perceptions of inappropriateness and caller distractions were independent risk factors for the delivery of bystander CPR. Further research around how call-takers navigate these barriers and encourage callers should be performed.

Background and Aims: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. Methods: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. Results: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. Conclusions: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.

Introduction: Anticoagulant-related nephropathy (ARN) is an increasingly recognized cause of acute kidney injury (AKI), initially associated with warfarin use. Supratherapeutic warfarin levels were implicated in kidney toxicity. With the widespread adoption of direct oral anticoagulants (DOACs), it becomes imperative to understand their potential risk for ARN and its clinical presentation. Case Presentation: We report a case of a 64-year-old male prescribed DOAC for paroxysmal atrial fibrillation management, presenting with heart failure and worsening AKI. Hematuria and mild proteinuria were also observed. Despite management attempts, AKI persisted, prompting a kidney biopsy. Histopathological examination revealed acute tubular injury with numerous intratubular red blood cell casts consistent with ARN. Additionally, findings indicative of IgA nephropathy (IgAN), including mesangial hypercellularity and IgA dominant deposition, were noted. Conclusion: This case underscores the emerging risk of ARN associated with DOACs and emphasizes the potential exacerbation of ARN in the presence of underlying glomerular diseases such as IgAN. Clinicians should maintain a high index of suspicion for ARN in patients on anticoagulation therapy, particularly DOACs, who present with AKI and urinary abnormalities, as early recognition and intervention are crucial in preventing further renal damage.

Objective: Intermittently scanned continuous glucose monitoring (isCGM) has revolutionised the care of people with diabetes but its uptake and benefits in older adults are not well known. We examined the impact of isCGM (Freestyle Libre, FSL) on glycaemic outcomes in younger (⩽65 years) and older adults (>65 years) with diabetes. Design and methods: In total, 2260 adult patients registered on the Libreview account at University Hospitals Birmingham NHS Foundation Trust, UK, were included. Inclusion criteria: all patients with type 1 and type 2 diabetes aged >18 years, use of isCGM >6 months, scanning at least 6 times/day. Demographics, diabetes history and glycaemic outcomes (time in range (TIR), time above range and time below range (TBR), estimated HbA1c, HbA1c at start and at end of study) were collected by accessing electronic patient records and Libreview. Outcomes were compared between age groups ⩽65 or >65 years old. Results: Most patients were of Caucasian ethnicity (⩽65 years 68%, >65 years 73%) and had type 1 diabetes. Mean duration of diabetes was 19.5 years (range 0–65 years) and 34.5 years (range 0–79 years) for ⩽65 and >65 years, respectively. Only a quarter of those ⩽65 years achieved (219/943; 23.2%) their age specific TIR target compared to 69% (78/113) of those >65 years cohort, while 70.1% (663/946) of ⩽65 years and 40.7% (46/113) of >65 years achieved their age-specific TBR target. When the less strict ⩽65 years TBR target was applied, 75% (85/113) of >65 years cohort achieved this. Conclusion: FSL use was associated with improved glycaemic outcomes across all age groups. Individualised targets may be needed to improve TBR in those aged >65 years.

Summary: Animal behavior emerges from collective dynamics of neurons, making it vulnerable to damage. Paradoxically, many organisms exhibit a remarkable ability to maintain significant behavior even after large-scale neural injury. Molecular underpinnings of this extreme robustness remain largely unknown. Here, we develop a quantitative pipeline to measure long-lasting latent states in planarian flatworm behaviors during whole-brain regeneration. By combining >20,000 animal trials with neural network modeling, we show that long-range volumetric peptidergic signals allow the planarian to rapidly restore coarse behavior output after large perturbations to the nervous system, while slow restoration of small-molecule neuromodulator functions refines precision. This relies on the different time and length scales of neuropeptide and small-molecule transmission to generate incoherent patterns of neural activity that competitively regulate behavior. Controlling behavior through opposing communication mechanisms creates a more robust system than either alone and may serve as a generalizable approach for constructing robust neural networks.

Summary: Whole-genome duplication (WGD) occurs in all kingdoms and impacts speciation, domestication, and cancer outcome. However, doubled DNA management can be challenging for nascent polyploids. The study of within-species polyploidy (autopolyploidy) permits focus on this DNA management aspect, decoupling it from the confounding effects of hybridization (in allopolyploid hybrids). How is autopolyploidy tolerated, and how do young polyploids stabilize? Here, we introduce a powerful model to address this: the genus Cochlearia, which has experienced many polyploidization events. We assess meiosis and other polyploid-relevant phenotypes, generate a chromosome-scale genome, and sequence 113 individuals from 33 ploidy-contrasting populations. We detect an obvious autopolyploidy-associated selection signal at kinetochore components and ion transporters. Modeling the selected alleles, we detail evidence of the kinetochore complex mediating adaptation to polyploidy. We compare candidates in independent autopolyploids across three genera separated by 40 million years, highlighting a common function at the process and gene levels, indicating evolutionary flexibility in response to polyploidy.

BackgroundAdolescence is a key developmental period that affects lifelong health and is impacted by adolescents regularly engaging with digital health information. Adolescents need digital health literacy (DHL) to effectively evaluate the quality and credibility of such information, and to navigate an increasingly complex digital health environment. Few educational resources exist to improve DHL, and few have involved adolescents during design. The co-design approach may hold utility through developing interventions with participants as design partners. ObjectiveThis project aimed to explore the co-design approach in developing an educational resource to improve adolescents’ DHL. MethodsAdolescents (12-17 years old) attended 4 interactive co-design workshops (June 2021-April 2022). Participant perspectives were gathered on DHL and the design of educational resources to improve it. Data generated were analyzed through content analysis to inform educational resource development. ResultsIn total, 27 participants from diverse backgrounds attended the workshops. Insight was gained into participants’ relationship with digital health information, including acceptance of its benefits and relevance, coupled with awareness of misinformation issues, revealing areas of DHL need. Participants provided suggestions for educational resource development that incorporated the most useful aspects of digital formats to develop skills across these domains. The following 4 themes were derived from participant perspectives: ease of access to digital health information, personal and social factors that impacted use, impacts of the plethora of digital information, and anonymity offered by digital sources. Initial participant evaluation of the developed educational resource was largely positive, including useful suggestions for improvement. ConclusionsCo-design elicited and translated authentic adolescent perspectives and design ideas into a functional educational resource. Insight into adolescents’ DHL needs generated targeted educational resource content, with engaging formats, designs, and storylines. Co-design holds promise as an important and empowering tool for developing interventions to improve adolescents’ DHL.

Abstract Chimpanzee insectivory is seasonally variable, with pronounced peaks or set seasonal periods of consumption observed in most chimpanzee communities. This variation is interesting given that chimpanzees invest considerable effort into complex tool‐using behaviors to acquire insect prey. Evidence suggests this seasonal variation is related to insect behavior, but few studies have been done to empirically examine this relationship. In this study, we assessed whether a seasonal pattern of termite fishing by Nigeria‐Cameroon chimpanzees (Pan troglodytes ellioti) in Mbam & Djerem National Park, Cameroon was driven by termite behavior. We measured termite presence and termite foraging activity monthly at seven termite mounds near Ganga Research Station from April 2022 to April 2023. Macroscopic fecal analysis and camera traps placed at each mound demonstrated termite fishing in this community occurred from March to June, with a rare smaller period of termite fishing in October 2021. Average monthly rainfall, average monthly temperature, and average monthly fruit availability were used to examine potential environmental factors that could impact termite fishing seasonality. Termite presence was significantly different between months with and without chimpanzee termite fishing (t‐test, −6.569, p

Abstract The liver plays a key role in the metabolism of lipoproteins, controlling both production and catabolism. To accelerate the development of new lipid‐lowering therapies in humans, it is essential to have a relevant in vitro study model available. The current hepatocyte‐like cells (HLCs) models derived from hiPSC can be used to model many genetically driven diseases but require further improvement to better recapitulate the complexity of liver functions. Here, we aimed to improve the maturation of HLCs using a three‐dimensional (3D) approach using Biomimesys®, a hyaluronic acid‐based hydroscaffold in which hiPSCs may directly form aggregates and differentiate toward a functional liver organoid model. After a 28‐day differentiation 3D protocol, we showed that many hepatic genes were upregulated in the 3D model (liver organoids) in comparison with the 2D model (HLCs). Liver organoids, grown on Biomimesys®, exhibited an autonomous cell organization, were composed of different cell types and displayed enhanced cytochromes P450 activities compared to HLCs. Regarding the functional capacities of these organoids, we showed that they were able to accumulate lipids (hepatic steatosis), internalize low‐density lipoprotein and secrete apolipoprotein B. Interestingly, we showed for the first time that this model was also able to produce apolipoprotein (a), the apolipoprotein (a) specific of Lp(a). This innovative hiPSC‐derived liver organoid model may serve as a relevant model for studying human lipopoprotein metabolism, including Lp(a).

BackgroundMultiple chemical sensitivity (MCS) develops in response to repeated small-level chemical exposures or a major exposure in a subset of people, who then experience symptoms that can range from mild to debilitating when exposed to chemicals. The arrival of the COVID-19 pandemic and the stringent health measures put in place may have increased the burden for those living with MCS, as it became more challenging to avoid chemicals that trigger their condition. ObjectiveThis study aimed to better understand the lived experience of Canadians living with MCS during the first year of the COVID-19 pandemic. MethodsAn online questionnaire was created to ask participants to compare daily living during the pandemic to before March 11, 2020. Data were collected in January and February 2021. Three areas were investigated: (1) environmental exposures to chemical triggers from ambient air (pollution from industry, farming, and traffic) and indoor air (the smell of cleaning products, cooking odors, and smoke); (2) access to, and satisfaction with, health care visits; and (3) how people experiencing MCS rated contact with their social network. ResultsIn all, 119 Canadians who had lived with MCS for more than a year completed the questionnaire. The participant sample was mostly female (86.6%, n=103) and highly educated, with 57.1% (n=68) having a university degree. Slightly more than half (57.1%, n=68) were older than 55 years. McNemar chi-square and Wilcoxon signed rank tests were used to evaluate if there were statistically significant changes before (“prepandemic period”) and after (“postpandemic period”) March 11, 2020. Perceived exposure to pollution from a highway or a road was significantly decreased from the prepandemic to postpandemic period (z=–3.347; P

Introduction Heterogeneity in reported outcomes of infants with oesophageal atresia (OA) with or without tracheo-oesophageal fistula (TOF) prevents effective data pooling. Core outcome sets (COS) have been developed for many conditions to standardise outcome reporting, facilitate meta-analysis and improve the relevance of research for patients and families. Our aim is to develop an internationally-agreed, comprehensive COS for OA-TOF, relevant from birth through to transition and adulthood.Methods and analysis A long list of outcomes will be generated using (1) a systematic review of existing studies on OA-TOF and (2) qualitative research with children (patients), adults (patients) and families involving focus groups, semistructured interviews and self-reported outcome activity packs. A two-phase Delphi survey will then be completed by four key stakeholder groups: (1) patients (paediatric and adult); (2) families; (3) healthcare professionals; and (4) researchers. Phase I will include stakeholders individually rating the importance and relevance of each long-listed outcome using a 9-point Likert scale, with the option to suggest additional outcomes not already included. During phase II, stakeholders will review summarised results from phase I relative to their own initial score and then will be asked to rescore the outcome based on this information. Responses from phase II will be summarised using descriptive statistics and a predefined definition of consensus for inclusion or exclusion of outcomes. Following the Delphi process, stakeholder experts will be invited to review data at a consensus meeting and agree on a COS for OA-TOF.Ethics and dissemination Ethical approval was sought through the Health Research Authority via the Integrated Research Application System, registration no. 297026. However, approval was deemed not to be required, so study sponsorship and oversight were provided by Alder Hey Children’s NHS Foundation Trust. The study has been prospectively registered with the COMET Initiative. The study will be published in an open access forum.

Purpose: Private supplementary tutoring, widely known as shadow education, has long been visible in East Asia, and now has spread to other parts of the world including Europe. This article maps the phenomenon, showing variations within Europe and analyzing its growth, underlying forces, and policy implications. Design/Approach/Methods: The article assembles a regional picture from available national sources. It focuses on the 28 members of the European Union. Findings: Within Europe, four subregions may be identified. Most prominent for the longest duration has been Southern Europe, pushed by political forces and cultural factors. In Eastern Europe, shadow education became prominent following the collapse of the Soviet Union and accompanying economic and social structures during which teachers and others had to earn extra incomes. In Western Europe, the advent of marketization alongside government schooling has fueled the growth of shadow education. Only in Northern Europe does shadow education remain modest in scale, but it is growing there too. Originality/Value: The article identifies forces underlying the growth of shadow education in Europe and highlights policy implications. By contributing this regional perspective to the wider literature on shadow education, the article permits juxtaposition with patterns in East Asia and elsewhere.

We isolated a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2 variant from a person with coronavirus disease 2019 recrudescence after nirmatrelvir/ritonavir treatment. Antiviral sensitivity and neutralizing antibody testing were performed with both parental SARS-CoV-2 and multiple variants of concern. We found that neither nirmatrelvir resistance nor absence of neutralizing immunity was a likely cause of the recrudescence.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a major health problem worldwide. Due to the fast emergence of SARS-CoV-2 variants, understanding the molecular mechanisms of viral pathogenesis and developing novel inhibitors are essential and urgent. Here, we investigated the potential roles of N6,2'-O-dimethyladenosine (m6Am), one of the most abundant modifications of eukaryotic messenger ribonucleic acid (mRNAs), in SARS-CoV-2 infection of human cells. Using genome-wide m6Am-exo-seq, RNA sequencing analysis, and Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing, we demonstrate that phosphorylated C-terminal domain (CTD)-interacting factor 1 (PCIF1), a cap-specific adenine N6-methyltransferase, plays a major role in facilitating infection of primary human lung epithelial cells and cell lines by SARS-CoV-2, variants of concern, and other coronaviruses. We show that PCIF1 promotes infection by sustaining expression of the coronavirus receptors angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) via m6Am-dependent mRNA stabilization. In PCIF1-depleted cells, both ACE2/TMPRSS2 expression and viral infection are rescued by re-expression of wild-type, but not catalytically inactive, PCIF1. These findings suggest a role for PCIF1 and cap m6Am in regulating SARS-CoV-2 susceptibility and identify a potential therapeutic target for prevention of infection.

Abstract Background Transferring residents from nursing homes (NHs) to emergency care facilities (ECFs) is often questioned as many are terminally ill and have access to onsite care. While some NH to ECF transfers have merit, avoiding other transfers may benefit residents and reduce healthcare system costs and provider burden. Despite many years of research in this area, differentiating warranted (i.e., appropriate) from unwarranted NH to ECF transfers remains challenging. In this article, we report consensus on warranted and unwarranted NH to ECF transfers scenarios. Methods A Delphi study was used to identify consensus regarding warranted and unwarranted NH to ECF transfers. Delphi participants included nurses (RNs) and medical doctors (MDs) from NHs, out-of-hours primary care clinics (OOHs), and hospital-based emergency departments. A list of 12 scenarios and 11 medical conditions was generated from the existing literature on causes and medical conditions leading to transfers, and pilot tested and refined prior to conducting the study. Three Delphi rounds were conducted, and data were analyzed using descriptive and comparative statistics. Results Seventy-nine experts consented to participate, of whom 56 (71%) completed all three Delphi rounds. Participants reached high or very high consensus on when to not transfer residents, except for scenarios regarding delirium, where only moderate consensus was attained. Conversely, except when pain relieving surgery was required, participants reached low agreement on scenarios depicting warranted NH to ECF transfers. Consensus opinions differ significantly between health professionals, participant gender, and rurality, for seven of the 23 transfer scenarios and medical conditions. Conclusions Transfers from nursing homes to emergency care facilities can be defined as warranted, discretionary, and unwarranted. These categories are based on the areas of consensus found in this Delphi study and are intended to operationalize the terms warranted and unwarranted transfers between nursing homes and emergency care facilities.