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Background/objectives: The Strengths and Difficulties Questionnaire (SDQ) is a widely used 25-item screening and diagnostic tool for behavioral and emotional problems in young people. Despite its popularity, evaluations of the SDQ's factor structure in adolescent populations have produced disparate results, and its relationships with theoretically related variables are rarely evaluated. In the present study, these two elements of validity were evaluated based on a large sample of Western Australian adolescents., Methods: Participants were 1489 adolescents, n = 623 males with a mean age of 13.79 years ( SD = 1.61) and n = 866 females, with a mean age of 14.29 years ( SD = 1.51). Participants completed the SDQ alongside measures of loneliness, sense of belonging, depression, bullying, and diagnostic status to evaluate its internal structure and correlations with theoretically related variables., Results: Confirmatory factor analyses supported the internal structure of the SDQ both for males and for females. Relationships between the SDQ subscale scores and those from theoretically related variables were also aligned with the instrument's underpinning framework., Conclusions: Despite the somewhat disparate results of previous studies, overall, this study supported the validity of the SDQ for use in the Western Australian context.

We have previously shown that mice with loss of C-type lectin-like type II (CLEC2), which have lymphatic dysfunction due to the role of CLEC2 in platelets for maintaining separation between the venous and lymphatic system, develop lung tertiary lymphoid organ (TLO) formation and lung injury that resembles an emphysema phenotype of chronic obstructive pulmonary disease (COPD). We now sought to investigate whether and how TLOs in these mice may play a pathogenic role in lung injury that is relevant to human disease. We found that inhibiting TLO formation using an anti-CD20 antibody in CLEC2-deficient mice partially blocked the development of emphysema. TLOs in CLEC2-deficient mice were rich in plasma cells and were a source of a broad array of autoantibodies. Chronic cigarette smoke exposure increased the size and number of lung TLOs in CLEC2-deficient mice, and was associated with increased markers of antigen presentation and maturation, leading to increased autoantibody deposition. Using lung tissue from COPD patients, we found an increase in lymphatic markers in patients with an emphysema phenotype and autoreactive TLOs compared to COPD patients without emphysema that lack prominent TLOs. Taken together, these results demonstrate that emphysema in mice with lymphatic dysfunction can be partially rescued by blocking TLO formation, and that these TLOs are source of autoantibodies that are exacerbated by cigarette smoke. Our work suggests that lymphatic dysfunction in mice may recapitulate some aspects an autoimmune emphysema phenotype that is seen in a subset of patients with COPD.

COVID-19 was a novel stressor that gave rise to pandemic related anxiety and increased the risk of mental health issues, particularly in youth. It is important to understand how such events contribute to psychological distress in young people to adequately intervene in the aftermath and to plan for future similar events. Using cross-sectional data from the CoSPACE Ireland study dataset this paper reports on the predictive relationship between COVID-19 anxiety and psychological distress for Irish adolescents ( N  = 314, M  = 14.05, SD  = 2.7, 11-18 years), while controlling for other influencing factors across multiple levels of a bioecological systems approach. Covariates were age, gender, ethnicity, social economic status, Peer Support, School Support and Parent-Child Closeness. Findings indicate that COVID-19 anxiety was a significant predictor of adolescents' psychological distress. Specifically, Consequence Anxiety (worries about the indirect consequences of COVID-19) was found to be a predictor of adolescents' psychological distress rather than Disease Anxiety (worries about the COVID-19 virus itself). Individual factors (e.g., age, ethnicity, special educational needs) and microsystem factors (e.g., parent child closeness, peer support) were also found to impact on adolescents' levels of psychological distress. A significant moderation analysis revealed that greater parent-child closeness reduced the strength of the positive association between Consequence Anxiety and psychological distress. These findings suggest that strategies to alleviate adolescents' psychological distress during pandemics should focus on reducing pandemic-related anxiety, specifically Consequence Anxiety. A multisystemic approach is also recommended to reduce the negative mental health impacts of the pandemic on adolescents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 McMahon, Gallagher, Dowling, Donnellan, Houghton, Ryan, O’Connor and Walsh.)

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the primary treatment for non-muscle-invasive bladder cancer (NMIBC), known to stimulate inflammatory cytokines, notably interferon (IFN)-γ. We observed that prolonged IFN-γ exposure fosters adaptive resistance in recurrent tumors, aiding immune evasion and tumor proliferation. We identify HLA-E and NKG2A, part of a novel NK and T cell checkpoint pathway, as key mediators of resistance in BCG-unresponsive NMIBC. IFN-γ enhances HLA-E and PD-L1 expression in recurrent tumors, with an enrichment of intra-tumoral NKG2A-expressing NK and CD8 T cells. CXCL9 + macrophages and dendritic cells and CXCL12-expressing stromal cells likely recruit CXCR3/CXCR4-expressing NK and T cells and CXCR7 + HLA-E HIGH tumor cells. NK and CD8 T cells remain functional within BCG-unresponsive tumors but are inhibited by HLA-E and PD-L1, providing a framework for combined NKG2A and PD-L1 blockade strategy for bladder-sparing treatment of BCG-unresponsive NMIBC., Competing Interests: Conflict of Interest Disclosure Statement: The authors declare no potential conflicts of interest.

The current study assessed the effectiveness of delivering safer gambling messaging to regular sport bettors on social media. It also assessed whether the content of the message impacted message effectiveness. A 3 × 2 mixed factorial design was employed, with 281 participants randomly assigned to follow one of three Twitter accounts. The accounts either sent out informational messages, self-appraisal messages or emotional self-efficacy messages. Participants reported betting behaviour from the two weeks prior to following the accounts, in addition to during the two-week intervention period, using information from their online gambling accounts. Participants reported readiness to change gambling behaviour pre and post the two-week intervention period. A significant main effect of intervention stage highlighted reductions in betting behaviour and increased readiness to change behaviour. However, there was no significant main effect of condition and no significant interaction between intervention stage and condition upon betting behaviour or readiness to change. The findings suggest receiving safer gambling messages on social media may lead to a reduction in betting behaviour. However, similar reductions in behaviour were observed in the experimental and control conditions. Further research is needed to clarify whether changes in behaviour observed in the current study would extend over a longer period of time., (© 2024. The Author(s).)

Introduction: The Child and Adolescent PsychProfiler version 5 (CAPP v5, 2014) is a measure for screening 14 common DSM-5 disorders in children and adolescents. The separation of Attention-Deficit/Hyperactivity Disorder (ADHD) and Specific Learning Disorder (SLD) by subtype results in 17 screening scales covering the 14 disorders. Theoretically then, the CAPP v5 should have a 17-factor structure, however, to date no published study has confirmed this. Additionally, there has been no comprehensive evaluation of the reliability and validity of the screening scales in this measure. These were examined across two different studies. Study 1 examined support for the 17-factor model of the parent-report version of the CAPP (CAPP-PRF) in a large group of adolescents from the general community. It also examined the internal consistency reliability and discriminant validity of the factors in this measure. Study 2 examined the validity of these factors in a clinic-referred group of adolescents., Methods: In Study 1, 951 parents completed the CAPP-PRF on behalf of their adolescents [mean (standard deviation) = 14.54 years (1.66 years)]. In Study 2, 173 parents completed the CAPP-PRF on behalf of their clinic-referred adolescent children [mean (standard deviation) = 14.5 years (1.84 years)]. Adolescents also completed a number of measures and tests for the purpose of assessing their behavior, IQ, and academic abilities., Results: The results in Study 1 supported a 17-factor model, and virtually all of the factors in this model showed acceptable reliability (alpha and omega coefficients), and discriminant validity. Study 2 demonstrated good support for the validity of the scales in the CAPP-PRF., Discussion: These findings indicate acceptable psychometric properties for the CAPP-PRF, and its utility for screening the more common DSM-5 disorders in children and adolescents., Competing Interests: SL was employed by Psychological & Educational Consultancy Services. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JR declared a shared affiliation with the authors RG and LK to the handling Editor at the time of review., (Copyright © 2024 Langsford, Gomez, Houghton and Karimi.)

In this study, a brief measure of four internal attributes found to protect against the impact of adverse life events on mental health was developed and validated. In addition, profiles of internal strengths that significantly predict mental health outcomes in young Chinese adults were identified. The results of exploratory and confirmatory factor analyses on data from 831 Chinese university students supported the proposed four-factor model of the ISALES. Participants in the current study fell into two clusters, with one cluster being higher than the other in all four internal strengths, with the former cluster demonstrating better overall mental health than those in the latter cluster. The ISALES is a promising instrument for use in clinical settings and may be used to identify individuals who are more 'at risk' of developing poor mental health in the aftermath of a negative life event. The use of the ISALES may permit tailored interventions and timely support to be provided to individuals within clinical settings.

Background: Recent studies have demonstrated that individuals hospitalized due to COVID-19 can be affected by "long-COVID" symptoms for as long as one year after discharge., Objectives: Our study objective is to identify data-driven clusters of patients using a novel, unsupervised machine learning technique., Methods: The study uses data from 437 patients hospitalized in New York City between March 3rd and May 15th of 2020. The data used was abstracted from medical records and collected from a follow-up survey for up to one-year post-hospitalization. Hospitalization data included demographics, comorbidities, and in-hospital complications. The survey collected long-COVID symptoms, and information on general health, social isolation, and loneliness. To perform the analysis, we created a graph by projecting the data onto eight principal components (PCs) and running the K-nearest neighbors algorithm. We then used Louvain's algorithm to partition this graph into non-overlapping clusters., Results: The cluster analysis produced four clusters with distinct health and social connectivity patterns. The first cluster (n = 141) consisted of patients with both long-COVID neurological symptoms (74%) and social isolation/loneliness. The second cluster (n = 137) consisted of healthy patients who were also more socially connected and not lonely. The third cluster (n = 96) contained patients with neurological symptoms who were socially connected but lonely, and the fourth cluster (n = 63) consisted entirely of patients who had traumatic COVID hospitalization, were intubated, suffered symptoms, but were socially connected and experienced recovery., Conclusion: The cluster analysis identified social isolation and loneliness as important features associated with long-COVID symptoms and recovery after hospitalization. It also confirms that social isolation and loneliness, though connected, are not necessarily the same. Physicians need to be aware of how social characteristics relate to long-COVID and patient's ability to cope with the resulting symptoms., (© 2024. The Author(s).)

Bovine tuberculosis (bTB), caused by Mycobacterium bovis infection, is a zoonotic disease in cattle that represents a significant ongoing challenge to cattle farming productivity and the livelihoods of livestock farmers in the UK. Vaccination of cattle with BCG could directly target the ability of M. bovis to proliferate within vaccinates, restricting bTB pathogenesis and onward disease transmission, and represent a step change in the tools available to help control bTB in farmed cattle. A Marketing Authorisation (MA) is required before a cattle BCG vaccine could be sold and supplied as a veterinary medicine within the UK and this requires comprehensive data supporting vaccine quality, efficacy and, most importantly, its safety. We carried out two independent Good Laboratory Practice (GLP) studies in which the safety of BCG vaccination in cattle was stringently tested through overdose and repeat vaccine administrations in young calves and pregnant heifers. Mild and generally short-lived reactions to vaccinations were observed in some animals, most commonly increases in body temperature and swelling at vaccine injection sites, but these did not have a negative impact on the overall health status of vaccinates. BCG was not shed in the saliva, faeces, milk or urine from vaccinated animals and its dissemination was limited to injection site tissues and associated lymph nodes. Overall, young calves and pregnant heifers vaccinated with BCG remained in good general health, and the vaccinated pregnant heifers had normal pregnancies and gave birth to healthy calves. Obtaining a Marketing Authorisation for a cattle BCG vaccine is a critical milestone in the progress towards the eventual use of BCG vaccination in cattle as an additional bTB control tool within the UK; these pivotal GLP vaccine safety studies generated the detailed and essential target animal safety data needed to support this., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024 Published by Elsevier Ltd.)

Type 1 diabetes-management can be considered an adolescent-parent collaboration. Given particular adolescent adherence challenges, it is integral that adolescent-parent dyadic relationships are investigated. Therefore, this study aimed to explore dyads' adjustment to type 1 diabetes, while examining the congruence/dissimilarity within these dyads. Semi-structured interviews were conducted with 10 dyads (20 individuals) separately. Interviews were transcribed verbatim and analysed with thematic analysis using a dyadic framework method. Findings suggested complex experiences of adjustment among parents and adolescents which reflect two main themes - Never-Ending Abyss of Management and Diabetes Integration, with three subthemes - A Life of Food Restrictions, Evolving Familial Bonds and Technology as easing the burden of Diabetes. Dyadic analyses revealed dyadic congruence across most themes. This study adds to the adjustment literature by providing a systemic perspective rarely presented in prior paediatric research., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

There is a need to identify the outcomes of changes in loneliness during adolescence, and to consider this within a multidimensional framework of loneliness. This study considered the effects of different trajectories of change in Isolation Loneliness and in Friendship Loneliness upon both positive wellbeing and symptoms of depression. To achieve this, 1782 (43% female; 12.92 years old at the start of the study, SD = 1.60) young people took part in a longitudinal study with four data points across 2 years. Four Isolation Loneliness trajectories and five Friendship Loneliness trajectories were identified. Youth who experienced low levels of Isolation Loneliness that subsequently increased appear to be at particular risk for poor outcomes. Similarly, initially high levels of Friendship Loneliness that decreased rapidly, or which began at a low level and only increased marginally, seem to also be a risk. Loneliness is a multi-dimensional construct and its development during adolescence impacts upon young people's depressive symptomatology and positive mental wellbeing., (© 2023. The Author(s).)

The lymphatic vasculature regulates lung homeostasis through drainage of fluid and trafficking of immune cells and plays a key role in the response to lung injury in several disease states. We have previously shown that lymphatic dysfunction occurs early in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) and that this is associated with increased thrombin and fibrin clots in lung lymph. However, the direct effects of CS and thrombin on lymphatic endothelial cells (LECs) in COPD are not entirely clear. Studies of the blood vasculature have shown that COPD is associated with increased thrombin after CS exposure that causes endothelial dysfunction characterized by changes in the expression of coagulation factors and leukocyte adhesion proteins. Here, we determined whether similar changes occur in LECs. We used an in vitro cell culture system and treated human lung microvascular lymphatic endothelial cells with cigarette smoke extract (CSE) and/or thrombin. We found that CSE treatment led to decreased fibrinolytic activity in LECs, which was associated with increased expression of plasminogen activator inhibitor 1 (PAI-1). LECs treated with both CSE and thrombin together had a decreased expression of tissue factor pathway inhibitor (TFPI) and increased expression of adhesion molecules. RNA sequencing of lung LECs isolated from mice exposed to CS also showed upregulation of prothrombotic and inflammatory pathways at both acute and chronic exposure time points. Analysis of publicly available single-cell RNA sequencing of LECs as well as immunohistochemical staining of lung tissue from COPD patients supported these data and showed increased expression of inflammatory markers in LECs from COPD patients compared to those from controls. These studies suggest that in parallel with blood vessels, the lymphatic endothelium undergoes inflammatory changes associated with CS exposure and increased thrombin in COPD. Further research is needed to unravel the mechanisms by which these changes affect lymphatic function and drive tissue injury in COPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Trivedi, Lu, Summers, Kim, Rhee, Houghton, Byers, Lis and Reed.)

Among the many social and emotional learning (SEL) interventions available, mindfulness-based interventions (MBIs) have become increasingly popular, particularly for preadolescent children who were once thought to not possess the metacognitive abilities or cognitive resources to benefit from such training. Although previous research syntheses indicate that MBIs show promise in promoting positive outcomes across a range of domains, the effectiveness of MBIs for preadolescent children may be masked by the effects of older children who have comprised the majority of samples in past meta-analyses. Hence, to better understand the impact of mindfulness-based training on preadolescent children (ages 6-12 years), the present study reviewed treatment effect estimates across a range of outcomes, including mindfulness, attention, metacognition and cognitive flexibility, emotional and behavioral regulation, academic achievement and school functioning, positive emotion and self-appraisal, negative emotion and subjective distress, externalizing problems, internalizing problems, social competence and prosocial behavior, and physical health. Thirty-two studies (n participants  = 3640) were identified and included in a random-effects meta-analyses. The results from multiple meta-analytical analyses conducted in the present study suggest that preadolescents have experienced significant benefits across attention, emotional and behavioral regulation, positive emotion and self-appraisal, and social competence and prosocial behavior (g = 0.19 to 0.39). However, the overall effect was deemed small (g = 0.34). Due to the lack of comparison studies with SEL interventions, it remains unclear whether MBIs are as effective as traditional approaches in promoting healthy development and academic achievement for preadolescent children. Additionally, results from the present meta-analysis suggest various recommendations for future studies to ensure a continued growth in understanding how MBIs can be used with children., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Postgraduate study can be mentally, physically and emotionally challenging. The levels of anxiety and depression in postgraduate students are much higher than those in the general population, and isolation can also be a problem, especially for students who are marginalised due to gender, race, sexuality, disability or being a first-generation and/or international student. These challenges are not new, but awareness of them has increased over the past decade, as have efforts by institutions to make students feel supported. Under the umbrella of a Doctoral Training Partnership, we developed a programme in which reflective practice is employed to help postgraduate students navigate work environments, deal with difficult supervisory or professional relationships, and improve their work-life balance. Additionally, this reflective practice is allowing the training partnership to tailor support to its students, enabling them to effectively nurture our next generation of bioscientists., Competing Interests: JT, JL, BC, DF, JH, SH, JF, LF, IG, SP, EH No competing interests declared, (© 2024, Tullet et al.)

Aim: The aim of this study was to explore the prominent factors that contributed to the development of child and adolescent eating disorder presentations during the COVID-19 pandemic., Methods: This was achieved through a qualitative analysis of interviews gathered from (1) adolescent patients diagnosed with an eating disorder (ED) during the COVID-19 pandemic (aged 13-18) ( n = 4), (2) parents of patients attending an ED service ( n = 7) and (3) clinicians working within a specialist child and adolescent ED support service ( n = 7). Reflexive thematic analysis was used to analyse the data and establish the most prominent aetiological factors reported., Results: The most prominent aetiological factors reported were (1) the accumulation of risk factors; (2) seeking control amid increased anxiety, stress and uncertainty; (3) social isolation; (4) an increased focus on exercise and "healthy eating"; (5) increased social media use promoting unhelpful attention towards ED triggers; and (6) a lack of both awareness and support services., Conclusion: During the COVID-19 pandemic, the quantity and severity of ED presentations increased. The current study uncovered six themes perceived by patients, parents and clinical staff that contributed to the aetiology of ED presentations during the COVID-19 pandemic. It is hoped that the insight gained through this research study into ED aetiology may act as a basis for further research and support ED awareness, prevention and intervention in the future.

Supporting organ transplant recipients' quality of life after surgery continues to be of interest to health researchers and applied practitioners. However, literature and guidance on the factors linked to quality of life in transplant recipient athletes remains underreported. This study aimed to identify significant predictors of quality of life in an international sample of organ transplant recipient athletes ( N  = 99, M age = 53 ± 14). Adopting a cross-sectional design, we collected the study data during the 2019 World Transplant Games which consisted of demographic items, health, and physical activity-related measures (i.e., task and ego orientation, fatigue severity, assessment of physical activity, physical activity enjoyment). Predictor variables were summarised into three categories: demographic factors, sport-related factors, and levels of fatigue with physical and mental quality of life functioning as the outcome variables. Hierarchical regression analyses exposed fatigue to exert a significant negative influence on both mental and physical quality of life perceptions explaining 49% and 64% of the variance in these variables respectively. Routine measurement and monitoring of transplant athletes' level of fatigue in sport settings are recommended due to the negative bearing on quality of life that may be a potential barrier to sport participation and enjoyment.

The purpose of this study was to produce a short-form measure of loneliness and assesses its prediction of depressive symptoms relative to a comprehensive measure. Western Australian adolescents completed the Friendship Related Loneliness and Isolation subscales of the Perth Aloneness Scale (PALs) three times over 18 months (T 1 n = 1538; T 2, n = 1683; T 3, n = 1406). Items were reduced while preserving predictability. Follow-up confirmatory factor analyses and predictive models with the reduced and full PALs were then tested. A reduced six-item scale (PALs-6) preserved the two-factor structure of the PALs and showed strong prediction of very elevated depressive symptoms (Sensitivity = 0.70, Specificity = 0.78, AUC = 0.81); it was less successful in predicting future symptoms (Sensitivity = 0.67, Specificity = 0.64, AUC = 0.74). The PALs-6 provides a brief measure of adolescent loneliness for clinicians and researchers that also predicts very elevated levels of depression., (© 2022. The Author(s).)

Objective: The aim of this systematic review was to synthesise qualitative evidence on young people's conceptualisation, utilisation and experiences of the therapeutic alliance in individual psychotherapy or counselling and its role in bringing about change., Method: The thematic synthesis method was used to synthesise data. The methodological quality of included studies was assessed using the CASP checklist for qualitative research., Results: Four superordinate analytical themes were generated: (1) valuable therapist qualities, (2) conditions for the development and maintenance of the therapeutic alliance, (3) therapeutic processes and (4) barriers to the development of the therapeutic alliance. Findings indicate that young people appreciated the uniqueness of the therapeutic relationship that provided a sense of safety, choice and autonomy. Flexibility and accessibility were noted as important elements of therapeutic alliance building as they elicited a sense of agency. Young people emphasised the non-linear nature of therapy and prioritised process variables such as improvement in self-understanding, self-efficacy and self-worth., Conclusion: The current systematic review is a comprehensive overview of qualitative studies of experiences of therapy from young people's perspectives. Important practical implications derived from this review as the role of autonomy in the change process and the formation and maintenance of the therapeutic relationship were outlined as important elements in youth therapy., (© 2023 The Authors. Clinical Psychology & Psychotherapy published by John Wiley & Sons Ltd.)

Background: Whilst some research has explored the impact of COVID-19 on gambling behaviour, little is yet known about online search behaviours for gambling during this period. The current study explored gambling-related online searches before, during and after the outbreak of the COVID-19 pandemic in the UK. We also assessed whether search trends were related to Gambling Commission behavioural data over the same period., Methods: Google Trends™ search data, covering thirty months from January 2020 to June 2022, for five gambling activities and five gambling operators were downloaded. Graphical displays of the weekly relative search values over this period were then produced to visualise trends in search terms, with key dates in COVID-19 policy and sporting events highlighted. Cross-correlations between seasonally adjusted monthly search data and behavioural indices were conducted., Results: Sharp increases in internet searches for poker, slots, and bingo were evident during the first lockdown in the UK, with operator searches sharply decreasing over this period. No changes in gambling activity searches were highlighted during subsequent lockdowns, although small increases in operator-based searches were detected. Strong positive correlations were found between search data and industry data for sports betting and poker but not for slots., Conclusions: Google Trends™ data may act as an indicator of population-level gambling behaviour. Substitution of preferred gambling activities for others may have occurred during the first lockdown when opportunities for sports betting were limited. Further research is needed to assess the effectiveness of internet search data in predicting gambling-related harm.

Very little is known about the impact of living with non-muscle invasive bladder cancer (NMIBC). NMIBC patients' experiences of their illness-in terms of their perceptions, coping strategies and psychological wellbeing-were explored. This study describes an interpretative phenomenological analysis (IPA) of individuals' accounts of living with NMIBC while on routine surveillance for cancer recurrence. Ten individuals took part in face-to-face semi-structured interviews. Three superordinate themes were derived from the data. The first theme, Being Diagnosed and Treated for NMIBC, concerned the observation that participants considered the physical implications, timeline and practicalities of their illness of primary importance and focused less on its psychological aspects. The second theme, Grappling with the Illness, outlined the impact of the doctor-patient relationship. The final theme, 'I don't treat it as a problem. I treat it as an issue', delineated how participants managed difficult emotions in the context of the illness. Findings from this study demonstrated that participants generally found effective ways to cope with their illness and experience of ongoing surveillance, though delay of emotional responses was common. Clinical implications for healthcare professionals are outlined including the importance of high-quality communication with the urology team.

This study explored how frequent gamblers perceive gambling marketing and the role they feel it has in their gambling behaviour. Ten frequent gamblers participated in semi-structured interviews oriented around their experiences of gambling marketing. An interpretative phenomenological analysis of the data led to three overarching themes: exploiting gambling marketing for personal gain; gambling marketing as a test of self-control; and safer gambling messages marketing perceived as ineffective. These themes encapsulated participants' views of gambling marketing as something they could take advantage of to increase their own gambling success. Marketing was also perceived as a test of self-control among self-identified experienced gamblers, although identified as a risk to those who are considered more vulnerable. Finally, safer gambling messages included within marketing was considered ineffective due to perceived insincerity and being seen as an 'afterthought' by marketers. In support of previous research, the current investigation highlights concerning narratives around self-control and perceived risk, as encapsulated within gambling marketing, and these are evident in the perceptions of frequent gamblers. Given gamblers' perceived lack of effectiveness of current safer gambling messages within marketing, future research should explore new avenues for safer gambling promotion., Competing Interests: The study was carried out as a part of the lead authors’ (SH) PhD studies. The PhD was funded by GambleAware. No other author has competing interests to declare., (Copyright: © 2023 Houghton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: There is little known about the clinicians' experience of collaboration using the Collaborative Assessment and Management of Suicide (CAMS) framework. This study aimed to give voice to the clinician experience., Method: A qualitative design utilised semi-structured interviews with ten psychologists who worked in a Suicide Assessment and Treatment Service (SATS) in Ireland which utilises the CAMS framework., Results: An Interpretative Phenomenological Analysis (IPA) approach revealed several important findings. The superordinate themes included 'Finding Safety', 'Regulation of the Self', 'Connecting', and 'Systemic Challenges'., Discussion: The CAMS framework plays an important role in providing a safe base for the clinician (in terms of understanding suicidality, in addition to the structures of the framework). It provides a mechanism in which to process difficult emotions, and a way of communicating a formulation of suicide to the treating team. Importantly, the CAMS emerged as facilitating a collaborative, therapeutic way of working.

Current ICD-11 descriptions for attention deficit hyperactivity disorder (ADHD) were recently published online, in the same year as the DSM-5-TR (text revised edition) was released. In this commentary, we compare and contrast the DSM-5/DSM-5-TR and ICD-11 diagnostic criteria, summarize important differences, and underscore their clinical and research implications. Overall, three major differences emerge: (1) The number of diagnostic criteria for inattention (IA), hyperactivity (HY) and impulsivity (IM) symptoms ( i.e. , DSM-5-TR has nine IA and nine HY/IM symptoms, whereas ICD-11 has 11 IA and 11 HY/IM sym-ptoms); (2) the clarity and standardization of diagnostic thresholds ( i.e. , the diagnostic thresholds for symptom count in IA and HY/IM domains are explicitly specified in DSM-5-TR, whereas in ICD-11 they are not); and (3) the partitioning of HY and IM symptoms into sub-dimensions ( i.e. , difference in partitioning HY and IM symptom domains relates to the differences between the current and previous editions of DSM and ICD, and this has important research implications). Currently, no ICD-11 based ADHD rating scales exist and while this absence represents an obstacle for respective research and clinical practice, it also presents opportunities for research development. This article highlights these challenges, possible remedies and novel research opportunities., Competing Interests: Conflict-of-interest statement: Nil. Wai Chen served as a reviewer for the DSM-5 Clinical and Public Health Committee during the DSM-5 revision; but this role did not and has not led to any conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Bovine tuberculosis (bTB) is a global disease of livestock that has damaging economic, animal health and public health consequences. Conventional bTB disease control strategies, based around the testing and slaughter of cattle infected with bTB, are typically used to help limit or reduce the transmission of this disease but in many low- and middle-income countries such strategies may often be economically unviable, culturally unacceptable or logistically impracticable. The use of vaccination to protect cattle against bTB could provide a potentially more affordable, ethically acceptable and practical additional disease control measure. The protective efficacy of the commercially produced and readily available human vaccine against tuberculosis ( Mycobacterium bovis Bacille Calmette-Guérin; BCG) in cattle has been demonstrated in many experimental laboratory and field studies. However, Good Laboratory Practice (GLP) studies assessing the safety of BCG vaccination in cattle have not previously been reported. We describe here the results of two GLP safety studies in which calves and lactating cows were vaccinated with BCG (Danish 1331 strain). From an animal health and welfare perspective, the results of these studies indicate that BCG vaccine is well tolerated in these categories of cattle with only transient and minor local or systemic reactions. Furthermore, there was no evidence that BCG was shed in raw milk, saliva or faeces collected from vaccinates and vaccination did not have a detrimental effect on milk yields in lactating cattle. These data, underpinned by GLP principles, further support the existing data on the safety of BCG vaccine in cattle and complement the abundant available cattle efficacy data for this potential cattle bTB vaccine., Competing Interests: The authors declare no competing interests., (Crown Copyright © 2022 Published by Elsevier Ltd.)

The prevalence of reported mental health problems among university students has increased at alarming rates in recent years. While various negative life events (from personal events such as relationship breakdowns to more global events such as COVID-19 [SARS-CoV-2] pandemic) have been found to be important predictors of poor mental health in this population, some individuals have been found robustly to fare better than others in confronting such events. Identifying factors that predict these individuals' mental health, along with the specific coping strategies they utilize may have significant practical implications when confronted by adverse events such as COVID-19. This study investigated relationships between the impact of the COVID-19 pandemic on 828 (453 females, 374 males, and one "Other") Chinese university students' mental health, and their internal strengths, personality characteristics, and demographic profiles. We also investigated whether students' use of specific coping strategies mediated these relationships. Stepwise multiple regression analyses (MRAs) and a path analysis revealed that students who resided in their home country, had higher levels of internal strengths, a lower level of neuroticism and a higher level of agreeableness and reported fewer negative mental health changes than did other respondents during COVID-19 in the second half of 2020. Self-regulation and withdrawal coping strategies were both important mediators of these relationships. These findings have important implications for universities in identifying and assisting students in the face of adverse events such as COVID-19., Competing Interests: The authors declare no conflict of interest.

Objectives: To describe the risk factors for SARS-CoV-2 infection in UK healthcare workers (HCWs)., Methods: We conducted a prospective sero-epidemiological study of HCWs at a major UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression., Results: 410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71]; p=0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42]; p=0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25]; p<0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 - 2·07; p<0·001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever, and myalgia; 31% of staff testing positive reported no prior symptoms., Conclusions: Risk of SARS-CoV-2 infection amongst HCWs is highly heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors., Competing Interests: Competing interests The authors declare that they have no competing interests, (Copyright © 2022. Published by Elsevier Ltd.)

Background: The impact of COVID-19 (SARS-CoV-2) pandemic school lockdowns on the mental health problems and feelings of loneliness of adolescents with neurodevelopmental disorders (NDDs) is hypothesized to be greater than that of their non-NDD peers. This two and a half year longitudinal study compared changes in the mental health and loneliness of Western Australian adolescents pre-COVID-19 (November 2018 and April 2019), immediately prior to COVID-19 school lockdowns (March 2020), and post schools reopening (July/August 2020)., Methods: An age-and-gender matched sample of 476 adolescents with-or-without NDDs completed online assessments for mental health and loneliness., Results: Adolescents with NDDs reported elevated levels of adverse mental health across all four waves of data collection. These young people experienced little change in mental health problems and feelings of loneliness over time, and any increase during school lockdowns returned to, or fell below pre-COVID-19 levels once schools reopened. In comparison, adolescents without NDDs experienced significant increases from a low baseline in depression symptoms, externalizing symptoms, feelings of isolation, and having a positive attitude to being alone, and evidenced a significant decline in positive mental wellbeing. Quality of friendships were unaffected by COVID-19 school lockdowns for all adolescents regardless of NDD status. Of the adolescents with NDDs, those with Attention-Deficit/Hyperactivity Disorder reported a significant increase in positive mental wellbeing following school lockdowns., Conclusions: Adolescents with NDDs emerged relatively unscathed from COVID-19 school lockdowns and the short term impacts associated with these were not maintained over time. These findings should be considered in the context of this study's geographical location and the unpredictability of school lockdowns. Learning to live with school lockdowns into the future may be a critical element for further investigation in the context of interventions., (© 2022 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Current dogma dictates that during adulthood, endothelial cells (ECs) are locked in an immutable stable homeostatic state. By contrast, herein we show that maintenance of EC fate and function are linked and active processes, which depend on the constitutive cooperativity of only two ETS-transcription factors (TFs) ERG and Fli1. While deletion of either Fli1 or ERG manifest subtle vascular dysfunction, their combined genetic deletion in adult EC results in acute vasculopathy and multiorgan failure, due to loss of EC fate and integrity, hyperinflammation, and spontaneous thrombosis, leading to death. ERG and Fli1 co-deficiency cause rapid transcriptional silencing of pan- and organotypic vascular core genes, with dysregulation of inflammation and coagulation pathways. Vascular hyperinflammation leads to impaired hematopoiesis with myeloid skewing. Accordingly, enforced ERG and FLI1 expression in adult human mesenchymal stromal cells activates vascular programs and functionality enabling engraftment of perfusable vascular network. GWAS-analysis identified vascular diseases are associated with FLI1/Erg mutations. Constitutive expression of ERG and Fli1 uphold EC fate, physiological function, and resilience in adult vasculature; while their functional loss can contribute to systemic human diseases., Competing Interests: Competing Interest Statement: Shahin Rafii is the co-founder and non-paid consultant to Angiocrine Bioscience, CA.

Background: Screening for depressive symptoms during adolescence is of high clinical significance. The shorter 12-item version of the Children's Depression Inventory (CDI 2:SR[S]) was specifically developed for this purpose. Evaluations of the CDI 2:SR[S] psychometrics are limited, however. The purpose of this study was to validate the CDI 2: SR[S] for use as a screening measure using Rasch analysis., Methods: The CDI 2: SR[S] was administered online to 1513 10-17 year old Western Australian adolescents (635 males, 878 females) from 11 schools. Overall fit, individual item fit, local response dependence, dimensionality, operation of response categories, and differential item functioning (DIF) were examined., Results: The Rasch analysis demonstrated the CDI 2: SR[S] has good reliability. Thresholds for all items were ordered, showing its three response categories functioned as intended. One item (I have to push myself to do schoolwork) showed misfit. No items were locally dependent. Two items (I am sad) and (I have to push myself to do schoolwork) showed DIF for gender. At the same level of depression, females reported being sad more than males, while males pushed themselves more to do schoolwork than did females. Adolescents (14-17 years) reported significantly higher mean depressive symptom scores than early adolescents (10-13 years)., Limitations: Sole reliance on adolescent's self-report and limited data about cultural backgrounds are limitations., Conclusions: The results support the interval scale measurement properties of the CDI 2: SR[S] and provides educators, clinicians and researchers with a screening measure to assess depressive symptoms in adolescents., (Copyright © 2022. Published by Elsevier B.V.)

The effect of SARS-CoV-2 infection on placental function is not well understood. Analysis of placentas from women who tested positive at delivery showed SARS-CoV-2 genomic and subgenomic RNA in 22 out of 52 placentas. Placentas from two mothers with symptomatic COVID-19 whose pregnancies resulted in adverse outcomes for the fetuses contained high levels of viral Alpha variant RNA. The RNA was localized to the trophoblasts that cover the fetal chorionic villi in direct contact with maternal blood. The intervillous spaces and villi were infiltrated with maternal macrophages and T cells. Transcriptome analysis showed an increased expression of chemokines and pathways associated with viral infection and inflammation. Infection of placental cultures with live SARS-CoV-2 and spike protein-pseudotyped lentivirus showed infection of syncytiotrophoblast and, in rare cases, endothelial cells mediated by ACE2 and Neuropilin-1. Viruses with Alpha, Beta, and Delta variant spikes infected the placental cultures at significantly greater levels., Competing Interests: O.E. is a scientific advisor and equity holder in Freenome, Owkin, Volastra Therapeutics, and One Three Biotech. R.E.S. is on the scientific advisory board of Miromatrix Inc and is a consultant and speaker for Alnylam Inc., (© 2022 The Author(s).)

The liver vascular network is patterned by sinusoidal and hepatocyte co-zonation. How intra-liver vessels acquire their hierarchical specialized functions is unknown. We study heterogeneity of hepatic vascular cells during mouse development through functional and single-cell RNA-sequencing. The acquisition of sinusoidal endothelial cell identity is initiated during early development and completed postnatally, originating from a pool of undifferentiated vascular progenitors at E12. The peri-natal induction of the transcription factor c-Maf is a critical switch for the sinusoidal identity determination. Endothelium-restricted deletion of c-Maf disrupts liver sinusoidal development, aberrantly expands postnatal liver hematopoiesis, promotes excessive postnatal sinusoidal proliferation, and aggravates liver pro-fibrotic sensitivity to chemical insult. Enforced c-Maf overexpression in generic human endothelial cells switches on a liver sinusoidal transcriptional program that maintains hepatocyte function. c-Maf represents an inducible intra-organotypic and niche-responsive molecular determinant of hepatic sinusoidal cell identity and lays the foundation for the strategies for vasculature-driven liver repair., Competing Interests: Declaration of interests S. Rafii is the co-founder and non-paid consultant to Angiocrine Bioscience, San Diego, CA. R.E.S. is on the scientific advisory board of Miromatrix Inc. and is a speaker and consultant for Alnylam Inc., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Tools to assess worry among adolescents exist but do not capture the content of worries. This study reports on the development of a brief, psychometrically sound measure of worry for use with adolescents. Phase 1 involved identification of 27 potential items from existing instruments as well as item generation identified in interviews with students, teachers, school psychologists, and parents. In Phase 2, the candidate items were completed by 835 Australian adolescents (317 males, 508 females, 10 unspecified; Mean age = 13.55, SD = 1.31) from Grades 5 to 10. These data were randomly split in half, and an exploratory factor analysis on the first half identified a two-factor solution with 12 items: Peer Relationships (6 items) and Academic Success and the Future (6 items). On the second half of the data, confirmatory factor analyses supported the factor structure and supported strong invariance across age, socioeconomic status, and presence/absence of a diagnosed neurodevelopmental disorder. Weak invariance was evident across sex. Differences across groups are reported as are correlations with indicators of psychological wellbeing. In conclusion, the Perth Adolescent Worry Scale provides both applied professionals and researchers with a short, easy-to-administer, and psychometrically strong instrument to evaluate adolescents' everyday worries., (© 2021. The Author(s).)

Individuals' coping strategies have a profound effect on how well they respond to negative life events. Despite this, most coping strategies instruments that are available currently have been developed exclusively in Western contexts. In the present study, a Coping Strategies Scale (CSS) for use with Chinese participants was developed and validated based on responses from 734 Chinese university students (334 male, 399 female, 1 other). Results supported a seven-factor structure for the CSS, which included the dimensions of Withdrawal, Positive Adaptation, Problem-solving, Disengagement, Prosocial Focus, Seeking Emotional Support, and Self-regulation. The results supported the validity of the seven-factor CSS in terms of its content, associated response processes, internal structure, and relationships with other variables. Based on these results, the CSS provides a psychometrically sound instrument for assessing the coping strategies used by Chinese adults in confronting potentially adverse psychological events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Chapman, Houghton and Lawrence.)

Severe acute lung injury has few treatment options and a high mortality rate. Upon injury, neutrophils infiltrate the lungs and form neutrophil extracellular traps (NETs), damaging the lungs and driving an exacerbated immune response. Unfortunately, no drug preventing NET formation has completed clinical development. Here, we report that disulfiram - an FDA-approved drug for alcohol use disorder - dramatically reduced NETs, increased survival, improved blood oxygenation, and reduced lung edema in a transfusion-related acute lung injury (TRALI) mouse model. We then tested whether disulfiram could confer protection in the context of SARS-CoV-2 infection, as NETs are elevated in patients with severe COVID-19. In SARS-CoV-2-infected golden hamsters, disulfiram reduced NETs and perivascular fibrosis in the lungs, and it downregulated innate immune and complement/coagulation pathways, suggesting that it could be beneficial for patients with COVID-19. In conclusion, an existing FDA-approved drug can block NET formation and improve disease course in 2 rodent models of lung injury for which treatment options are limited.

Background: Impostor phenomenon is a term used to describe feelings of intellectual and professional fraudulence. The Clance Impostor Phenomenon Scale and the Leary Impostorism Scale are two self-report measures used to determine whether an individual experiences impostor phenomenon. This study examined the psychometric properties of both measures in healthcare simulation educators., Methods: The study sample comprised 148 educators, 114 (77%) females, 34 (23%) males, who completed an online version of each instrument. Exploratory factor analysis was used to examine the factor structure of the Clance Impostor Phenomenon Scale and the Leary Impostorism Scale., Results: Exploratory factor analysis revealed that for both instruments a one-factor solution best fit the data, suggesting all items in both measures fit onto a single theoretical construct. Both instruments demonstrated high internal reliability, with the Cronbach's alpha for the Clance Impostor Phenomenon Scale being α = .96 and the Leary Impostorism Scale α = .95., Conclusions: This study suggests that impostor phenomenon as measured by the Clance Impostor Phenomenon Scale and the Leary Impostorism Scale is a unidimensional construct among healthcare simulation educators. With a growing interest in impostor phenomenon, the present findings will assist researchers to evaluate the phenomenon in healthcare settings., (© 2022. The Author(s).)

Introduction: Longitudinal research examining the impact of coronavirus disease 2019 (COVID-19) school closures on the mental health of adolescents is scarce. Prolonged periods of physical and social isolation because of such restrictions may have impacted heavily on adolescents' mental health and loneliness., Methods: The current study addresses a major gap by examining the impact of school closures on the mental health and loneliness of 785, 10- to 17-year-old Western Australian adolescents (mean age = 14.1, SD = 1.31), who were surveyed across four time points: twice before COVID-19, once as schools closed, and once post reopening of schools. Pre- and post-COVID-19 changes in mental health and loneliness were compared using linear mixed models. Random intercept cross-lagged panel models (RI-CLPMs) assessed temporal associations between loneliness, depression symptoms, and positive mental wellbeing., Results: Compared with pre-COVID-19 symptom levels, there were significant increases in depression symptoms, internalizing and externalizing symptoms, and a significant decrease in positive mental wellbeing at different points over time. Symptom change over time differed according to gender and pre-COVID-19 symptom severity. Significant increases in positive attitudes towards being alone and feelings of isolation occurred at different points over time. Gender differences were evident. RI-CLPMs highlighted the predictive significance of friendship quality and having a negative attitude towards being alone over time in relation to depression symptoms. A positive or negative attitude towards being alone was predictive of positive mental wellbeing over time., Conclusion: Findings provide evidence that COVID-19-related school closures adversely affected adolescents' mental health and feelings of loneliness., (© 2022 The Authors. Journal of Adolescence published by Wiley Periodicals LLC on behalf of Foundation for Professionals in Services to Adolescents.)

Adult stem cells maintain regenerative tissue structure and function by producing tissue-specific progeny, but the factors that preserve their tissue identities are not well understood. The small and large intestines differ markedly in cell composition and function, reflecting their distinct stem cell populations. Here we show that SATB2, a colon-restricted chromatin factor, singularly preserves LGR5 + adult colonic stem cell and epithelial identity in mice and humans. Satb2 loss in adult mice leads to stable conversion of colonic stem cells into small intestine ileal-like stem cells and replacement of the colonic mucosa with one that resembles the ileum. Conversely, SATB2 confers colonic properties on the mouse ileum. Human colonic organoids also adopt ileal characteristics upon SATB2 loss. SATB2 regulates colonic identity in part by modulating enhancer binding of the intestinal transcription factors CDX2 and HNF4A. Our study uncovers a conserved core regulator of colonic stem cells able to mediate cross-tissue plasticity in mature intestines., Competing Interests: Declaration of interests A patent application related to this work is pending at Weill Cornell Medicine., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Assessing the scope and severity of threats is necessary for evaluating impacts on populations to inform conservation planning. Quantitative threat assessment often requires monitoring programs that provide reliable data over relevant spatial and temporal scales, yet such programs can be difficult to justify until there is an apparent stressor. Leveraging efforts of wildlife management agencies to record winter counts of hibernating bats, we collated data for 5 species from over 200 sites across 27 U.S. states and 2 Canadian provinces from 1995 to 2018 to determine the impact of white-nose syndrome (WNS), a deadly disease of hibernating bats. We estimated declines of winter counts of bat colonies at sites where the invasive fungus that causes WNS (Pseudogymnoascus destructans) had been detected to assess the threat impact of WNS. Three species undergoing species status assessment by the U.S. Fish and Wildlife Service (Myotis septentrionalis, Myotis lucifugus, and Perimyotis subflavus) declined by more than 90%, which warrants classifying the severity of the WNS threat as extreme based on criteria used by NatureServe. The scope of the WNS threat as defined by NatureServe criteria was large (36% of Myotis lucifugus range) to pervasive (79% of Myotis septentrionalis range) for these species. Declines for 2 other species (Myotis sodalis and Eptesicus fuscus) were less severe but still qualified as moderate to serious based on NatureServe criteria. Data-sharing across jurisdictions provided a comprehensive evaluation of scope and severity of the threat of WNS and indicated regional differences that can inform response efforts at international, national, and state or provincial jurisdictions. We assessed the threat impact of an emerging infectious disease by uniting monitoring efforts across jurisdictional boundaries and demonstrated the importance of coordinated monitoring programs, such as the North American Bat Monitoring Program (NABat), for data-driven conservation assessments and planning., (© 2021 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Aims: The proportion of UK oncology healthcare professionals (HCPs) infected with SARS-CoV-2 during the COVID-19 pandemic's first wave is unknown. The primary aim of this study was to determine the SARS-CoV-2 infection and seroprevalence rates among HCPs., Materials and Methods: Patient-facing oncology HCPs working at three large UK hospitals during the COVID-19 pandemic's first wave underwent polymerase chain reaction (PCR) and antibody testing [Luminex and point-of-care (POC) tests] on two occasions 28 days apart (June-July 2020)., Results: In total, 434 HCPs were recruited: nurses (58.3%), doctors (21.2%), radiographers (10.4%), administrators (10.1%); 26.3% reported prior symptoms suggestive of SARS-CoV-2. All participants were PCR negative during the study, but 18.4% were Luminex seropositive on day 1, of whom 42.5% were POC seropositive. Nurses had the highest seropositive prevalence trend (21.3%, P = 0.2). Thirty-eight per cent of seropositive HCPs reported previous SARS-CoV-2 symptoms: 1.9 times higher odds than seronegative HCPs (P = 0.01). Of 400 participants retested on day 28, 13.3% were Luminex seropositive (92.5% previously, 7.5% newly). Thirty-two per cent of initially seropositive HCPs were seronegative on day 28., Conclusion: In this large cohort of PCR-negative patient-facing oncology HCPs, almost one in five were SARS-CoV-2 antibody positive at the start of the pandemic's first wave. Our findings that one in three seropositive HCPs retested 28 days later became seronegative support regular SARS-CoV-2 PCR and antibody testing until widespread immunity is achieved by effective vaccination., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Heart injury has been reported in up to 20% of COVID-19 patients, yet the cause of myocardial histopathology remains unknown. Here, using an established in vivo hamster model, we demonstrate that SARS-CoV-2 can be detected in cardiomyocytes of infected animals. Furthermore, we found damaged cardiomyocytes in hamsters and COVID-19 autopsy samples. To explore the mechanism, we show that both human pluripotent stem cell-derived cardiomyocytes (hPSC-derived CMs) and adult cardiomyocytes (CMs) can be productively infected by SARS-CoV-2, leading to secretion of the monocyte chemoattractant cytokine CCL2 and subsequent monocyte recruitment. Increased CCL2 expression and monocyte infiltration was also observed in the hearts of infected hamsters. Although infected CMs suffer damage, we find that the presence of macrophages significantly reduces SARS-CoV-2-infected CMs. Overall, our study provides direct evidence that SARS-CoV-2 infects CMs in vivo and suggests a mechanism of immune cell infiltration and histopathology in heart tissues of COVID-19 patients., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is marked by airway inflammation and airspace enlargement (emphysema) leading to airflow obstruction and eventual respiratory failure. Microvasculature dysfunction is associated with COPD/emphysema. However, it is not known if abnormal endothelium drives COPD/emphysema pathology and/or if correcting endothelial dysfunction has therapeutic potential. Here, we show the centrality of endothelial cells to the pathogenesis of COPD/emphysema in human tissue and using an elastase-induced murine model of emphysema. Airspace disease showed significant endothelial cell loss, and transcriptional profiling suggested an apoptotic, angiogenic, and inflammatory state. This alveolar destruction was rescued by intravenous delivery of healthy lung endothelial cells. Leucine-rich α-2-glycoprotein-1 (LRG1) was a driver of emphysema, and deletion of Lrg1 from endothelial cells rescued vascular rarefaction and alveolar regression. Hence, targeting endothelial cell biology through regenerative methods and/or inhibition of the LRG1 pathway may represent strategies of immense potential for the treatment of COPD/emphysema., Competing Interests: Disclosures: D.J. Nolan reported personal fees from Angiocrine Bioscience outside the submitted work; in addition, D.J. Nolan had a patent number 8,465,732 issued (Angiocrine Bioscience) and a patent number 9,944,897 issued; and is an employee and equity holder of Angiocrine Bioscience. M. Ginsberg reported personal fees from Angiocrine Bioscience outside the submitted work; in addition, M. Ginsberg had a patent to 8,465,732 issued and a patent to 9,944,897 issued. In addition, M. Ginsberg is a current employee and equity holder of Angiocrine Bioscience. F.J. Martinez reported non-financial support from ProterrixBio, Nitto, Zambon; "other" from Afferent/Merck, Biogen, Veracyte, Prometic, Bridge Biotherapeutics, and Abbvie; grants from Gilead; and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Chiesi, Sunovion, Patara/Respivant, Bayer, Promedior/Roche, Teva, Col Behring, DevPro, IQVIA, Sanofi/Regeneron, United Therapeutics, and Novartis outside the submitted work. S.M. Cloonan reported grants from National Institute of Health, National Heart, Blood and Lung Institute (NHLBI), and Science Foundation Ireland (SFI), and personal fees from Pharmacosmos outside the submitted work; in addition, S.M. Cloonan had a patent number 10,905,682 issued. S. Rafii reported non-financial support from Angiocrine Bioscience during the conduct of the study; non-financial support from Angiocrine Bioscience outside the submitted work; and had a patent to E4ORF1 Endothelial cell infusion for organ repair licensed (Angiocrine Bioscience). A.M.K. Choi is a cofounder and equity stock holder for Proterris, which develops therapeutic uses for carbon monoxide. A.M.K. Choi has a use patent on CO. Additionally, A.M.K. Choi has a patent in COPD. No other disclosures were reported., (© 2021 Hisata et al.)

[Figure: see text].

Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with negative social and occupational outcomes across the life course. However, there has been limited population-based research that quantifies the impact of ADHD on academic achievement and academic trajectories., Aims: To compare academic performance and academic trajectories of students with ADHD with students without a mental disorder., Sample: Data were drawn from Young Minds Matter, a national population-based sample of 6,310 Australian children and adolescents aged 4-17 years. Using linked achievement test data, the academic performance and trajectories of 327 students with ADHD were compared with those of 3,916 students without a mental disorder., Methods: Survey data were combined with scores on national standardized tests for literacy and numeracy over an 8-year period., Results: In Year 3, students with ADHD were on average 1 year behind students with no mental disorder in reading and numeracy, and 9 months behind in writing. In Year 9, the gaps were much larger with students with ADHD on average 2.5 years behind in reading, 3 years behind in numeracy, and 4.5 years behind in writing., Conclusions: Students with ADHD have substantially lower achievement in reading, writing, and numeracy. Writing was the most adversely affected domain. For example, in Year 9 students with ADHD were on average writing at a Year 5 level. Children and adolescents with ADHD need substantial support to manage inattention, impulsivity, and hyperactivity. Skilled remediation in literacy and numeracy is required throughout all school years., (© 2020 The British Psychological Society.)

Attention Deficit/hyperactivity disorder (ADHD) is conceptualized differently in the Diagnostic and Statistical Manual (DSM-5), the International Classification of Diseases-10 (ICD-10), and the Hierarchical Taxonomy of Psychopathology (HiTOP) frameworks. This study applied independent cluster confirmatory factor analysis (ICM-CFA), exploratory structure equation model with target rotation (ESEM), and the S-1 bi-factor CFA approaches to evaluate seven ADHD models yielded by different combinations of these taxonomic frameworks. Parents and teachers of a community sample of children (between 6 and 12 years of age) completed the Disruptive Behavior Rating Scale (for ADHD symptoms) and the Strengths and Difficulties Questionnaire (for validation). Our findings for both parent and teacher ratings provided the most support for the S-1 bi-factor CFA model comprised of (i) a g-factor based on ICD-10 impulsivity symptoms as the reference indicators and (ii) inattention and hyperactivity as specific factors. However, the hyperactivity-specific factor lacked clarity and reliability. Thus, our findings indicate that ADHD is best viewed as a disorder primarily reflecting impulsivity, though with a separable inattention (but no hyperactivity) component, i.e., "ADID (attention deficit/impulsivity disorder)." This model aligns with the HiTOP proposals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gomez, Liu, Krueger, Stavropoulos, Downs, Preece, Houghton and Chen.)

Objective: To evaluate the characteristics of patients with autoimmune disease with hypogammaglobulinemia following rituximab (RTX) and describe their long-term outcomes, including those who commenced immunoglobulin replacement therapy., Methods: Patients received RTX for autoimmune disease between 2003 and 2012 with immunoglobulin G (IgG) <7g/L were included in this retrospective series. Hypogammaglobulinemia was classified by nadir IgG subgroups of 5 to <7g/L (mild), 3 to <5g/L (moderate) and <3g/L (severe). Characteristics of patients were compared across subgroups and examined for factors associated with greater likelihood of long term hypogammaglobulinemia or immunoglobulin replacement., Results: 142 patients were included; 101 (71%) had anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis (AAV), 18 (13%) systemic lupus erythematosus (SLE) and 23 (16%) other conditions. Mean follow-up was 97.2 months from first RTX. Hypogammaglobulinemia continued to be identified during long-term follow-up. Median time to IgG <5g/L was 22.5 months. Greater likelihood of moderate hypogammaglobulinemia (IgG <5g/L) and/or use of immunoglobulin replacement therapy at 60 months was observed in patients with prior cyclophosphamide exposure (odds ratio (OR) 3.60 [95% confidence interval (CI) 1.03 - 12.53], glucocorticoid use at 12 months [OR 7.48 (95% CI 1.28 - 43.55], lower nadir IgG within 12 months of RTX commencement [OR 0.68 (95% CI 0.51 - 0.90)] and female sex [OR 8.57 (95% CI 2.07 - 35.43)]. Immunoglobulin replacement was commenced in 29/142 (20%) and associated with reduction in infection rates, but not severe infection rates., Conclusion: Hypogammaglobulinemia continues to occur in long-term follow-up post-RTX. In patients with recurrent infections, immunoglobulin replacement reduced rates of non-severe infections., Competing Interests: JT reports grants from Arthritis Australia (funded by Australian Rheumatology Association and Roche) and National Health and Medical Research Council during the conduct of this study. DK reports other support from CSL Behring, Shire/Takeda, Charities Fund Addenbrookes Hospital Cambridge and Grifols outside the submitted work, and membership of Immunoglobulin Demand Management Assessment Panel for National Health Service UK, membership of Clinical Reference Group for Immunology and Allergy National Health Service, England since 2019. AM reports personal fees and other support from CSL Behring, and other support from Takeda outside submitted work. DJ reports grants from Roche/Genentech during the conduct of the study, personal fees from Astra-Zeneca, Aurinia, and Boehringer, grants and personal fees from Chemocentryx, grants and personal fees from GSK, and grants from Sanofi outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with one of the authors, DJ., (Copyright © 2021 Tieu, Smith, Gopaluni, Kumararatne, McClure, Manson, Houghton and Jayne.)

Brain microvascular endothelial cells (BMECs) possess unique properties that are crucial for many functions of the blood-brain-barrier (BBB) including maintenance of brain homeostasis and regulation of interactions between the brain and immune system. The generation of a pure population of putative brain microvascular endothelial cells from human pluripotent stem cell sources (iBMECs) has been described to meet the need for reliable and reproducible brain endothelial cells in vitro . Human pluripotent stem cells (hPSCs), embryonic or induced, can be differentiated into large quantities of specialized cells in order to study development and model disease. These hPSC-derived iBMECs display endothelial-like properties, such as tube formation and low-density lipoprotein uptake, high transendothelial electrical resistance (TEER), and barrier-like efflux transporter activities. Over time, the de novo generation of an organotypic endothelial cell from hPSCs has aroused controversies. This perspective article highlights the developments made in the field of hPSC derived brain endothelial cells as well as where experimental data are lacking, and what concerns have emerged since their initial description., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lu, Barcia Durán, Houghton, Rafii, Redmond and Lis.)