Long-Term Effectiveness and Durability of COVID-19 Vaccination Among Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: COVID-19 vaccination prevents severe disease in most patients with inflammatory bowel disease (IBD), but immunosuppressive medications can blunt serologic response. We followed adults with IBD for >1 year post-COVID-19 vaccination to describe factors associated with SARS-CoV-2 infection after vaccination, evaluate for a protective SARS-CoV-2 antibody level, characterize SARS-CoV-2 antibody persistence, and identify factors associated with humoral immune response durability. METHODS: Using a prospective cohort of COVID-19 immunized adults with IBD, we analyzed factors associated with SARS-CoV-2 infection after vaccination. We evaluated for an association between SARS-CoV-2 antibody level 12 weeks postvaccination and subsequent SARS-CoV-2 infection and assessed for a threshold of protection using receiver-operating characteristic curve analysis. We then conducted a separate analysis evaluating factors associated with persistence of SARS-CoV-2 antibodies 52 weeks postimmunization. RESULTS: Almost half (43%) of 1869 participants developed COVID-19 after vaccination, but most infections were mild, and <1% required hospitalization. Older age and corticosteroid use were associated with a decreased risk of SARS-CoV-2 infection postvaccination (50-59 years of age vs 18-29 years of age: adjusted hazard ratio, 0.57; 95% confidence interval, 0.44-0.74; steroid users vs nonusers: adjusted hazard ratio, 0.58; 95% confidence interval, 0.39-0.87). Most (98%) participants had detectable antibody levels at 52 weeks postvaccination. Antibody levels at 12 weeks and number of vaccine doses were positively associated with higher antibody levels at 52 weeks, while anti-tumor necrosis factor α therapy was negatively associated. CONCLUSIONS: COVID-19 vaccination generates an effective and durable protective response for the vast majority of adults with IBD, including vulnerable populations such as corticosteroid users and older individuals. Patients with IBD benefit from COVID-19 booster vaccination.

Genomes of Endotrypanum monterogeii from Panama and Zelonia costaricensis from Brazil: Expansion of Multigene Families in Leishmaniinae Parasites That Are Close Relatives of Leishmania spp.

The Leishmaniinae subfamily of the Trypanosomatidae contains both genus Zelonia (monoxenous) and Endotrypanum (dixenous). They are amongst the nearest known relatives of Leishmania, which comprises many human pathogens widespread in the developing world. These closely related lineages are models for the genomic biology of monoxenous and dixenous parasites. Herein, we used comparative genomics to identify the orthologous groups (OGs) shared among 26 Leishmaniinae species to investigate gene family expansion/contraction and applied two phylogenomic approaches to confirm relationships within the subfamily. The Endotrypanum monterogeii and Zelonia costaricensis genomes were assembled, with sizes of 29.9 Mb and 38.0 Mb and 9.711 and 12.201 predicted protein-coding genes, respectively. The genome of E. monterogeii displayed a higher number of multicopy cell surface protein families, including glycoprotein 63 and glycoprotein 46, compared to Leishmania spp. The genome of Z. costaricensis presents expansions of BT1 and amino acid transporters and proteins containing leucine-rich repeat domains, as well as a loss of ABC-type transporters. In total, 415 and 85 lineage-specific OGs were identified in Z. costaricensis and E. monterogeii. The evolutionary relationships within the subfamily were confirmed using the supermatrix (3384 protein-coding genes) and supertree methods. Overall, this study showed new expansions of multigene families in monoxenous and dixenous parasites of the subfamily Leishmaniinae.

#DeOlhoNosCorais: a polygonal annotated dataset to optimize coral monitoring.

Corals are colonial animals within the Phylum Cnidaria that form coral reefs, playing a significant role in marine environments by providing habitat for fish, mollusks, crustaceans, sponges, algae, and other organisms. Global climate changes are causing more intense and frequent thermal stress events, leading to corals losing their color due to the disruption of a symbiotic relationship with photosynthetic endosymbionts. Given the importance of corals to the marine environment, monitoring coral reefs is critical to understanding their response to anthropogenic impacts. Most coral monitoring activities involve underwater photographs, which can be costly to generate on large spatial scales and require processing and analysis that may be time-consuming. The Marine Ecology Laboratory (LECOM) at the Federal University of Rio Grande do Norte (UFRN) developed the project "#DeOlhoNosCorais" which encourages users to post photos of coral reefs on their social media (Instagram) using this hashtag, enabling people without previous scientific training to contribute to coral monitoring. The laboratory team identifies the species and gathers information on coral health along the Brazilian coast by analyzing each picture posted on social media. To optimize this process, we conducted baseline experiments for image classification and semantic segmentation. We analyzed the classification results of three different machine learning models using the Local Interpretable Model-agnostic Explanations (LIME) algorithm. The best results were achieved by combining EfficientNet for feature extraction and Logistic Regression for classification. Regarding semantic segmentation, the U-Net Pix2Pix model produced a pixel-level accuracy of 86%. Our results indicate that this tool can enhance image selection for coral monitoring purposes and open several perspectives for improving classification performance. Furthermore, our findings can be expanded by incorporating other datasets to create a tool that streamlines the time and cost associated with analyzing coral reef images across various regions.

Applications of Human Pluripotent Stem Cell-Derived Skin Organoids in Dermatology.

Pluripotent stem cells have the potential to become any cell type, and recently, they have been used to create organoids that can recapitulate several pertinent features of human organs. Skin organoids have been developed that possess many of the crucial accessory organs, including hair follicles, sebaceous glands, nerves, fat, and melanocytes. These skin organoids present the opportunity to study skin development and disease as well as perform screens to identify new drug candidates. In the future, skin organoids might augment clinical practice by serving as source material for transplantation to treat wounds or other conditions. Nevertheless, several limitations, such as the lengthy differentiation protocol, which can result in heterogeneous products, must first be addressed before the full potential of skin organoids can be realized. The purpose of this article is to provide a broad overview of skin organoids so that a broader audience can become familiar with this technology, which has important implications for dermatologic research and medicine.

A comparison of sleep-wake patterns among school-age children and adolescents in Hong Kong before and during the COVID-19 pandemic.

STUDY OBJECTIVES: The lifestyles change of children and adolescents during the COVID-19 pandemic due to antipandemic measures can affect their sleep health. Existing studies have used convenient samples and focused on the initial months of the pandemic, leaving a knowledge gap on changes in young people's sleep patterns under the "new normal" under COVID-19. METHODS: As part of a territory-wide epidemiological study in Hong Kong, this cross-sectional study recruited primary and secondary school students by stratified random sampling. Sleep parameters were collected using the structured diagnostic interview for sleep patterns and disorders. We investigated the pandemic's effects on sleep parameters by comparing data of participants recruited pre-COVID and those recruited during COVID using multivariate regression, adjusting for age, sex, household income, seasonality, and presence of mental disorders, and the moderators and mediators of the effects. RESULTS: Between September 1, 2019 and June 2, 2021, 791 primary and 442 secondary school students were recruited and analyzed. Primary school and secondary school participants assessed before COVID had a longer sleep latency on school days (95% confidence interval [CI] = 1.0-5.2 minutes, adjusted P-value = .010; and 95% CI= 3.9-13.0 minutes, adjusted P-value = .004, respectively) and nonschool days (95% CI = 1.7-7.2 minutes, adjusted P-value = .005; 95% CI = 3.4-13.7 minutes, adjusted P-value = .014, respectively). Low household income was a moderator for later bedtime (adjusted P-value = .032) and later sleep onset (adjusted P-value = .043) during nonschool days among secondary school students. CONCLUSIONS: Changes associated with COVID have a widespread and enduring effect on the sleep health of school-aged students in Hong Kong. Household income plays a role in adolescent sleep health resilience, and the impact of antiepidemic measures on the health gaps of the youth should be considered. CITATION: Chau SWH, Hussain S, Chan SSM, et al. A comparison of sleep-wake patterns among school-age children and adolescents in Hong Kong before and during the COVID-19 pandemic. J Clin Sleep Med. 2023;19(4):749-757.

Humoral Immune Response and Safety of SARS-CoV-2 Vaccination in Pediatric Inflammatory Bowel Disease.

INTRODUCTION: Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD. METHODS: We recruited children with IBD, ages 5-17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization. RESULTS: Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 µg/mL (SD 67) and a median of 22 µg/mL (interquartile range 12-38). In adjusted analyses, older age ( P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone ( P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant. DISCUSSION: Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination.

Low Rates of Breakthrough COVID-19 Infection After SARS-CoV-2 Vaccination in Patients With Inflammatory Bowel Disease.

We demonstrate low rates of breakthrough coronavirus disease 2019 (COVID-19) infection and mild course of illness following severe acute respiratory syndrome coronavirus 2 vaccination in a large cohort of inflammatory bowel disease patients. Residence in southern United States and lower median anti-receptor binding antibody level were associated with development of COVID-19.

Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets.

Infections of humans with the protozoan parasite Toxoplasma gondii (T. gondii) can lead to the disease's development, even in an asymptomatic status. However, the mechanisms that result in these clinical outcomes after infection are poorly understood. This study aimed to explore the molecular pathogenesis of toxoplasmosis-related inflammation through next-generation sequencing, to assess RNA expression profiles in peripheral blood from 5 female patients with chronic toxoplasmosis and 5 healthy female controls. All plasma samples were analyzed for anti-Toxoplasma IgG and IgM antibody titers by using electrochemiluminescence. Detection of acute and chronic toxoplasmosis was carried out using the ELISA IgG avidity. We evaluated the levels of INF-γ, IL-2, IL-12, TNF-α, IL-10, and IL-1ß in culture supernatants of Peripheral Blood Mononuclear Cells infected with Toxoplasma lysate antigen (TLA) prepared with tachyzoites of strain T. gondii RH. Differential expression analysis was performed using DESeq2, pathway and enrichment analysis of DEGs was done on WEB-based Gene SeT AnaLysis Toolkit (WebGestalt) and Protein-protein interaction was carried out using NetworkAnalyst with STRING. In older people with chronic asymptomatic infection, a significant difference in the levels of inflammatory cytokines INF-γ and IL-2 was observed compared to seronegative individuals. Our results revealed differences in the regulation of critical biological processes involved in host responses to chronic T. gondii infection. Gene ontology analysis revealed several biologically relevant inflammatory and immune-related pathways.

Anti-Carbamylated Protein (Anti-CarP) Antibodies in Patients Evaluated for Suspected Rheumatoid Arthritis.

(1) Background: Anti-carbamylated protein (CarP) antibodies have been studied as novel markers to aid in the diagnosis and prognosis of rheumatoid arthritis. (2) Methods: A total of 265 samples were included in the evaluation, for which 98 had results for anti-cyclic citrullinated peptide (CCP), 86 for rheumatoid factor (RF), and 212 for 14-3-3 eta protein. Anti-CarP antibodies were measured using a fetal calf serum-based single-step assay (research use only, Inova Diagnostics, San Diego, CA). (3) Results: Anti-CarP antibodies were significantly higher and more frequent in anti-CCP3.1+ (p = 0.0025), RF+ (p = 0.0043) and 14-3-3 eta+ (p = 0.028) samples compared to the negative counterpart group. In addition, isolated anti-CarP positivity occurred in samples negative for anti-CCP3.1, RF, or 14-3-3 eta. When anti-CarP antibodies were compared to each of the RF, anti-CCP3.1, and 14-3-3 eta by receiver operating characteristic (ROC) analyses, the area under the curve (AUC) values of 0.71 (RF), 0.68 (anti-CCP3.1), and 0.59 (14-3-3 eta), respectively, demonstrated a moderate correlation. Using an UpSet plot, we determined that 10.6% of the samples with available results for anti-CCP3.1, RF, and anti-CarP showed triple positivity. (4) Conclusions: Anti-carbamylated protein (anti-CarP) antibodies can be detected in anti-CCP, RF and 14-3-3 eta-positive and -negative patients, potentially identifying specific subsets of patients.

Disentangling the relationship of gut microbiota, functional gastrointestinal disorders and autism: a case-control study on prepubertal Chinese boys.

Emerging evidence of an altered gut microbiome in autism spectrum disorder (ASD) suggests a pathomechanism through the gut-brain axis despite the inconsistent microbiome profile reported across studies. One of the knowledge gaps in the existing ASD microbiota studies is the lack of systematic exploration of the role of comorbid functional gastrointestinal disorder (FGID) in the association of ASD and altered gut microbiome. Consequently, 92 ASD and 112 age-matched typically developing (TD) boys were profiled on general psychopathology, FGID status by Rome IV classification, and gut microbiota using 16S ribosomal RNA amplicon sequencing at the V4 hypervariable region. Compared to TD, a significant decrease in the within-sample abundance of taxa was observed in ASD, regardless of FGID status. The microbiota of ASD FGID+ and ASD FGID- clustered apart from the TD groups. The microbiota of ASD FGID+ also showed qualitative differences from that of ASD FGID- and had the highest-level Firmicutes: Bacteroidetes ratio, which was paralleled by elevated levels of anxiety and overall psychopathology. The altered gastrointestinal microbiota composition in ASD appeared to be independent of comorbid FGID. Further studies should address how FGID may mediate neuropsychiatric symptoms in ASD through inflammation along the microbiota-gut-brain axis.

Adverse childhood experiences and adolescent drug use in the UK: The moderating role of socioeconomic position and ethnicity.

Rationale: There is a paucity of prospective UK studies exploring the role of Adverse Childhood Experiences (ACEs) on adolescent teenage drug use and even less is known about the complex interplay between ACEs and adolescent social, demographic, and economic characteristics. To address these gaps, we use rich longitudinal data from the nationally representative Millennium Cohort Study. Methods: Sex-stratified survey logistic regression modelling was applied using data from 9,476 adolescents and their parents to examine associations between ACEs between ages 3 and 14 years and drug use at ages 14 and 17 years. We a) explore the extent to which associations are robust to adjustment for ethnicity, family income, parental social class, and parental education, b) examine whether associations differ by these factors, and c) estimate the proportion of drug use at ages 14 and 17 years attributable to ACEs after controlling for these factors. Results: Half of MCS cohort members had been exposed to at least one ACE and approximately 1 in 11 were exposed to 3+ ACEs. Multivariable analyses suggest that ACEs were associated with a higher likelihood of drug use at age 14 than age 17, especially for girls. No evidence was found that either advantaged socio-economic position or ethnicity acted as a buffer against the negative effects of ACEs in relation to adolescent drug use. Finally, we found that prevention of exposure to sexual violence, bullying and violence within the household (if causal) is more important for girls' drug use at age 14 than age 17. Conclusions: ACEs are associated with adolescent drug use with potential consequences on wider aspects of young people's lives, regardless of their social, ethnic, or economic background, adding further urgency to the need to reduce the incidence of these negative experiences.

School-Based Mental Health Initiative: Potentials and Challenges for Child and Adolescent Mental Health.

School-based mental health support services allow children and adolescents easy access to services without requirement of traveling to clinics and hospitals. We describe a School Mental Health Support Scheme (SMHSS) piloted in Hong Kong and discuss the challenges and learnings from the experience. This conceptual paper argues that accessibility is not the only advantage of such services. Teachers are significant others in child development, alongside with families. They play a central role in impacting the children's/adolescents' needs for competence and adult attachment, while schools provide an expanded social network of peers for one's social relationship. The fulfillment of these needs has powerful implications in the mental health of the children/adolescents. Teachers can help students to develop a sense of competence with self-worth and self-identity via providing guidance and feedback, whether they be on one's strengths or weaknesses, with acceptance, tolerance and unconditional positive regard. Particularly, the latter define a form of teacher-student relationship or adult attachment that offers the children/adolescents emotional security and nourishment, protecting them from failings and adversities. Teachers can also supervise and guide their students' social development with peers at schools. A recent meta-analysis has found preliminary evidence that those school-based mental health services integrated into the teachers' routine teaching activities are more effective. Teachers, who are overworked and stressed by the schools' overemphasis on academics and grades, have yet to fully grasp their unique roles in supporting students with mental health needs. This paper ends by advocating a paradigm shift in which both the healthcare professionals and educators should forge a mutually beneficial collaboration in jointly enhancing the mental health of children/adolescents at schools.

A comparison of sleep-wake patterns among school-age children and adolescents in Hong Kong before and during the COVID-19 pandemic

BackgroundLifestyle of children and adolescents have changed extensively during the COVID-19 pandemic due to school suspension and social distancing measures, which can affect their sleep health. Existing studies in the area used convenient samples and focused on the initial months of the pandemic. MethodAs part of a territory-wide epidemiological study in Hong Kong, this cross-sectional study recruited primary and secondary school students by stratified random sampling. We investigated the pandemics effects on sleep parameters using multivariate regression, adjusting for age, sex, household income, seasonality and presence of mental disorders, and the effects moderators and mediators. FindingsBetween September 1, 2019 and June 2, 2021, 791 primary and 442 school students were recruited and analysed. After correcting for multiple testing, being assessed during COVID predicted a longer sleep latency in primary and secondary school students in school days (95% CI = 1.0-5.2 minutes, adjusted p-value = 0.010; and 95% CI= 3.9-13.0 minutes, adjusted p-value =0.004, respectively) and non-school days (95% CI = 1.7-7.2 minutes, adjusted p-value = 0.005; 95% CI = 3.4-13.7 minutes, adjusted p-value = 0.014, respectively). Low household income was a moderator for later bedtime (adjusted p-value = 0.032) and later sleep onset (adjusted p-value = 0.043) during non-school days among secondary school students. Sex and digital leisure time were not moderator and mediator of the pandemics effect on sleep parameters, respectively. InterpretationChanges associated with the COVID-19 pandemic have a widespread and enduring effect on sleep health of school-aged students in Hong Kong. Household income play a role in adolescents sleep healths resilience against these changes, and anti-epidemic measures effects on the health gap of the youth should be considered. FundingGovernment of the Hong Kong Special Administrative Region, Food and Health Bureau, Health and Medical Research Fund (Ref. No.: MHS-P1(Part 1)-CUHK).

BNT-15: Revised Performance Validity Cutoffs and Proposed Clinical Classification Ranges.

BACKGROUND: Abbreviated neurocognitive tests offer a practical alternative to full-length versions but often lack clear interpretive guidelines, thereby limiting their clinical utility. OBJECTIVE: To replicate validity cutoffs for the Boston Naming Test-Short Form (BNT-15) and to introduce a clinical classification system for the BNT-15 as a measure of object-naming skills. METHOD: We collected data from 43 university students and 46 clinical patients. Classification accuracy was computed against psychometrically defined criterion groups. Clinical classification ranges were developed using a z -score transformation. RESULTS: Previously suggested validity cutoffs (≤11 and ≤12) produced comparable classification accuracy among the university students. However, a more conservative cutoff (≤10) was needed with the clinical patients to contain the false-positive rate (0.20-0.38 sensitivity at 0.92-0.96 specificity). As a measure of cognitive ability, a perfect BNT-15 score suggests above average performance; ≤11 suggests clinically significant deficits. Demographically adjusted prorated BNT-15 T-scores correlated strongly (0.86) with the newly developed z -scores. CONCLUSION: Given its brevity (<5 minutes), ease of administration and scoring, the BNT-15 can function as a useful and cost-effective screening measure for both object-naming/English proficiency and performance validity. The proposed clinical classification ranges provide useful guidelines for practitioners.

On the Cutting Edge of Oral Cancer Prevention: Finding Risk-Predictive Markers in Precancerous Lesions by Longitudinal Studies.

Early identification and management of precancerous lesions at high risk of developing cancers is the most effective and economical way to reduce the incidence, mortality, and morbidity of cancers as well as minimizing treatment-related complications, including pain, impaired functions, and disfiguration. Reliable cancer-risk-predictive markers play an important role in enabling evidence-based decision making as well as providing mechanistic insight into the malignant conversion of precancerous lesions. The focus of this article is to review updates on markers that may predict the risk of oral premalignant lesions (OPLs) in developing into oral squamous cell carcinomas (OSCCs), which can logically be discovered only by prospective or retrospective longitudinal studies that analyze pre-progression OPL samples with long-term follow-up outcomes. These risk-predictive markers are different from those that prognosticate the survival outcome of cancers after they have been diagnosed and treated, or those that differentiate between different lesion types and stages. Up-to-date knowledge on cancer-risk-predictive markers discovered by longitudinally followed studies will be reviewed. The goal of this endeavor is to use this information as a starting point to address some key challenges limiting our progress in this area in the hope of achieving effective translation of research discoveries into new clinical interventions.

Factors Affecting Initial Humoral Immune Response to SARS-CoV-2 Vaccines Among Patients With Inflammatory Bowel Diseases.

INTRODUCTION: Although an additional coronavirus disease 2019 vaccine dose for immunocompromised persons has been recommended in some countries, further data to guide vaccination strategies for patients with inflammatory bowel disease (IBD) are urgently needed. We sought to identify factors affecting initial humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with IBD. METHODS: In this prospective cohort of SARS-CoV-2 immunized patients with IBD, we evaluated associations between participant age, sex, vaccine type, medication use, and the presence of a detectable antireceptor binding domain antibody and quantitative antibody level. RESULTS: In total, 1,909 participants were included (1,123, 692, and 94 received BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively) of whom 96% achieved a positive antibody response. On multivariable analysis, factors associated with lack of antibody response were older age (P = 0.043), BNT162b2 vs mRNA-1273 (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.0-3.9), and combination therapy with anti-TNF and 6MP, azathioprine, or methotrexate (OR 4.2, 95% CI 2.4-7.3). The use of 5-aminosalicylate or sulfasalazine (OR 0.3, 95% CI 0.1-0.8) and ustekinumab (OR 0.2, 95% CI 0.05-0.8) was associated with decreased odds of lacking antibody response. DISCUSSION: Most patients with IBD mount an initial response to SARS-CoV-2 vaccination; however, older patients and those treated with anti-TNF and immunomodulator have blunted responses and may benefit the most from an additional vaccine dose. Patients treated with other classes of immunosuppressive medications have more robust initial immune responses to vaccination. These data should inform key decisions about patient selection for additional coronavirus disease 2019 vaccine doses in patients with IBD.

Autism Diagnostic Interview-Revised Within DSM-5 Framework: Test of Reliability and Validity in Chinese Children.

This study examines the psychometric properties of the Autism Diagnostic Interview-Revised (ADI-R) in the context of DSM-5 in a sample of Chinese children. Using re-mapped ADI-R items and algorithms matched to DSM-5 criteria, and administering to children with autism spectrum disorder (ASD) with and without intellectual disability, attention-deficit hyperactivity disorder, and typically developing, it evidenced high sensitivity and specificity. However, similar to DSM-IV algorithm, the DSM-5 algorithms were better at classifying ASD among children with intellectual disability than among those without intellectual disability. With the DSM-5's recognition of the spectrum nature of ASD, the performance of the ADI-R can be improved by having finer gradations in the ADI-R scoring and adding more items on the restricted and repetitve behavior domain.

Prediction models in gynaecology: Transparent reporting needed for clinical application.

The clinical application of prediction models is increasing within the field of gynaecology and obstetrics. This is mostly due to the fact that clinicians and patients prefer individualized counselling and person specific, more objective outcome assessment. To prevent using inadequate models, it is important to construct and perform prediction model studies correctly. Therefore, the TRIPOD statement (the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) was developed. The aim of this review is to obtain an overview of the existing published prediction models for benign gynaecology and to investigate to what extent these studies meet the TRIPOD criteria. We performed a literature search in the databases PubMed, Embase and Cochrane Library from inception to August 2020. Searching the cross-references of the relevant studies within our search identified additional articles. Publications were included if the aim of the study was to develop a multivariable prediction model within the field of benign gynaecology. Two independent reviewers extracted the data. Analysis of the studies was performed by using a checklist derived from the TRIPOD criteria. Based on our search, 2487 studies were selected, including potential duplications. Eventually, a total of twenty-two studies were selected. 91% of these studies handled their predictors by univariable analysis before developing a multivariable prediction model. Fifteen studies described having missing data, but not all of them (9%) handled these missing data. Four different internal validation methods were used in twenty studies. Fifteen studies (68%) had prediction models with a C-index ≥ 0.7, which indicates a good model. Half of the studies (50%) did not measure the calibration, overall performance was described in two studies (9%). External validation was performed in 9% of the studies. The correct development of a prediction model within benign gynaecology and subsequent transparent reporting of the model development is important to facilitate clinical use. Without transparent reporting, wrong assumptions can be made leading to incorrect application of a specific prediction model. This overview shows that excepting carrying out an external validation, only one article met all the criteria. Therefore, we strongly recommend use of the TRIPOD criteria for developing and validating a prediction model (study). In addition, prior to publication, content experts should critically and statistically review the prediction model. If too many criteria are not met, refusing publication should be considered.

An elevated anxiety level among prepubertal autistic boys with non-treatment-seeking functional gastrointestinal disorders: A case-control study.

Children with autism commonly suffer from comorbid functional gastrointestinal disorders (FGID) and anxiety. The raised prevalence of both conditions in autism suggests complex reciprocal relationships, which are seldom explored in non-treatment-seeking FGID. The relationships between subtypes of FGID and anxiety are also unclear. This study recruited boys with autism and age-matched typically developing (TD) boys, aged 4-11 years, who were not actively seeking help for gastrointestinal problems. Their parents completed the Rome IV Diagnostic Questionnaires for Pediatric FGID. Four groups of children with and without autism/FGID were identified and compared on their anxiety level using the Spence children's anxiety scale. In 69 boys with autism and 69 age-matched TD boys, FGID were identified in 22 and 16 boys, respectively. ANCOVA demonstrated a significant interaction effect of autism and FGID on anxiety (F[1, 129] = 5.43, p = 0.021), while conditional logistic regression identified an interaction effect of autism and anxiety on the odds of FGID (OR 1.038, 95% CI 1.002-1.075, p = 0.038). Explorative post hoc analysis showed higher anxiety in functional nausea and vomiting disorder (p = 0.033) and functional abdominal pain disorder (p = 0.029) among boys with autism than TD boys with the same respective subtypes of FGID. In summary, among prepubertal boys with autism, the presence of FGID that are non-treatment-seeking in nature, has a significantly stronger association with higher levels of anxiety than TD boys. The strength of association may be more prominent in subtypes of FGID. Possible pathomechanisms including the underlying microbiota spectra and inflammatory paths should be explored in future studies. LAY SUMMARY: Anxiety and gastrointestinal problems are common symptoms in autism. Given that gut health could be linked to emotions, their association in young boys with autism was studied. The presence of nausea vomiting, or abdominal pain were associated with raised anxiety among boys with autism, yet this was not observed in typically developing boys. This suggests that anxiety among autistic children could be partly explained by the presence of FGID.

Genetic Overlap Between Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in SHANK2 Gene.

Background: Recent findings indicated a high comorbidity between attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), as well as shared genetic influences on them. The latter might contribute at least partly to the former clinical scenario. This study aimed at investigating whether SHANK genes were potential pleiotropic genes to the two said disorders, underlying their genetic overlap. Methods: This study recruited 298 boys with ADHD (including 256 family trios of 1 ADHD boy and his 2 biological parents), 134 boys with ASD, 109 boys with both ADHD and ASD, and 232 typically developing boys as community controls. They were aged between 6 and 11 years old. Results: There was no significant difference in allele frequency of a number of single nucleotide polymorphisms (SNPs) in SHANK2/SHANK3 between the three clinical groups (ADHD, ASD, and ADHD + ASD) and between the two control groups (community controls and pseudo-controls), respectively. The three clinical groups and the two control groups were thus, respectively, combined. A comparison between the two aggregated samples identified significant evidence of disease association for three SHANK2 SNPs with both ADHD and ASD, even after multiple testing correction: rs11236616 (OR = 0.762, permuted p = 0.0376), rs7106631 (OR = 0.720, permuted p = 0.0034), and rs9888288 (OR = 0.770, permuted p = 0.0407). Comparisons among individual groups pointed to a similar trend of findings. Conclusion: SHANK2 could be considered a potential pleiotropic gene underlying the genetic overlap between ADHD and ASD. This might contribute partly to their high comorbidity in the afflicted children.