Genomic architecture of autism from comprehensive whole-genome sequence annotation.

Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.

Exploring Ligand Effects on Structure, Bonding, and Photolytic Hydride Transfer of Cationic Gold(I) Bridging Hydride Complexes of Molybdocene and Tungstenocene.

A diverse family of heterobimetallic bridging hydride adducts of the type [LAu(µ-H)2MCp2][X] (L = 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene, IPr; 1,3-bis(1-adamantyl)imidazole-2-ylidene, IAd; 1,3-bis(2,6-di-iso-propylphenyl)-5,5-dimethyl-4,6-diketopyrimidinyl-2-ylidene, DippDAC; triphenylphosphine, PPh3; 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl, tBuXPhos; X = SbF6-, BF4- or TfO-) was synthesized by reacting group VI metallocene dihydrides Cp2MH2 (Cp = cyclopentadienyl anion; M = Mo, W) with cationic gold(I) complexes [LAu(NCMe)][X]. Trimetallic [L'Au2(µ-H)2WCp2][X]2 and tetrametallic [L'Au2{(µ-H)2WCp2}2] [X]2 complexes (L' = rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene or bis(diphenylphosphinomethane)) were obtained by reacting digold [L'{Au(NCMe)}2][X]2 with Cp2WH2 in a 1:1 and a 1:2 stoichiometry. Accessing such a broad structural diversity allowed us to pinpoint roles played by the ancillary ligands and group VI metals on the bonding properties of this family of bridging hydrides. In particular, a clear effect of the ligand on the interaction energy and electronic structure was observed, with important implications on photolytic reactivity. UV or visible light irradiation, indeed, leads to the selective cleavage of the heterobimetallic Au(µ-H)2M arrangement and formation of molecular gold hydrides. The photolysis was found to be chromoselective (wavelength-dependent), which can be ascribed to different charge redistributions upon excitation to the first (Kasha's reactivity) and higher (anti-Kasha's reactivity) excited states.

Diversity trends in traumatic brain injury clinical trials in the United States.

BACKGROUND: This study aims to understand the demographic representation of patients in Traumatic Brain Injury (TBI) clinical trials by evaluating the proportions of patients from various demographic categories amongst completed TBI clinical trials in the United States. METHODS: ClinicalTrials.gov was queried for active TBI clinical trials. One hundred and eight completed trials in the United States were selected based on inclusion criteria, and information regarding intervention, setting, age, sex, race, and ethnicity was extracted. 2002-2006 TBI incidence data was obtained from the CDC. Chi-squared testing was applied to analyze the relationship between distributions of race and sex in the collected clinical trials and the national TBI data, and logistic regression was conducted to identify variables that may predict reporting of race or ethnicity. RESULTS: About 53.7% of selected clinical trials reported racial data and 34.3% reported ethnicity data. Logistic regression identified that clinical trials in defined phases were more likely to report racial data (p = 0.047 [1.015, 9.603]). CONCLUSION: Current TBI trials do not consistently report race or ethnicity data. Future efforts to ensure equitable representation in clinical trials may involve reform of recruitment processes and accountability measures implemented within the grant application process to ensure proper racial and ethnicity data reporting.

The Role of Surveillance in Predicting Fracture in Pediatric Patients With Incidentally Discovered Nonossifying Fibromas and Fibrous Cortical Defects: Is It Worth It?

BACKGROUND: Nonossifying fibroma (NOF) and fibrous cortical defect (FCDs), the most common benign pediatric bone lesions, are usually incidental x-ray findings. Surveillance of characteristic lesions has been recommended to monitor for enlargement and assess fracture risk. However, no accepted fracture risk prediction guidelines exist, so indications for prophylactic surgery are unclear. The study's purposes were to (1) characterize the timing of NOF/FCD-associated fractures, (2) quantify the resources devoted to surveillance, and (3) evaluate the potential for surveillance to prevent pathologic fracture. METHODS: A single institution retrospective review was conducted to identify pediatric patients (below 18 y old) with clinical-radiographic documentation of an NOF or FCD diagnosis from 2012 to 2020. Patients who presented with fracture were tallied but excluded from the surveillance analysis. Patients without at least one follow-up visit were also excluded. Lesional radiographic features were characterized on initial imaging. The number of visits and imaging studies devoted to surveillance were tabulated. The number of fractures and prophylactic surgeries were recorded to quantify the potential of surveillance to prevent pathologic fractures. RESULTS: The study population presenting without fracture consisted of 301 patients with 364 lesions with a mean follow-up of 20 months. By contrast, over the same period, 38 patients presented with NOF/FCD associated pathologic fractures. Surveillance included 1037 additional imaging tests over 1311 follow-up visits, or on average, 3.4 imaging studies and 4.4 visits per patient. During surveillance, only 2 (0.55%) lesions fractured. Another 10/364 (2.8%) patients underwent curettage and grafting, suggesting that-at best-the potential for preventing pathologic fracture by surveillance, assuming all 10 patients who underwent surgery would have subsequently fractured along with the 2 documented fractures, is 3.3% of lesions (12/364). CONCLUSIONS: The small number of fractures and surgeries during the follow-up period probably does not justify additional resources for surveillance beyond the initial visit, except in symptomatic patients with large lesions. However, subsequent visits may play a role in educating patients and their families regarding the natural history of these lesions. LEVEL OF EVIDENCE: Prognostic Level II-retrospective study.

Acute Kidney Injury in Subarachnoid Hemorrhage: Exploring its Clinical Significance and Prognostic Implications.

OBJECTIVES: Subarachnoid hemorrhage (SAH) from spontaneous rupture of an aneurysm is a debilitating condition with high morbidity and mortality. Patients with SAH remain understudied, particularly concerning the evaluation of incidence and consequences of subsequent acute kidney injury (AKI). In this study, we aim to explore the risk factors and outcomes of AKI in patients with SAH. MATERIALS AND METHODS: International Classification of Diseases, 9th Edition and 10th Edition (ICD-10-CM) codes were used to query the National Inpatient Sample (NIS) for patients with a diagnosis of SAH between 2010-2019. Subgroup analysis was stratified by AKI diagnosis during the same hospitalization. AKI and non-AKI groups were assessed for baseline clinical characteristics, interventions, complications, and outcomes. Descriptive statistics, multivariate regressions, and propensity score-matching were performed using IBM SPSS 28. NEED TO MENTION NIH-SSS RESULTS: Of 76,553 patients diagnosed with nontraumatic SAH between 2010-2019, 10,634 (13.89%) had a comorbid diagnosis of AKI. Patients with AKI were older (p<0.01) and more often obese (p < 0.01), compared to the non-AKI group. A multivariate regression found the diagnosis of AKI to be independently correlated with poor functional outcome (p<0.001), above average length of stay (p < 0.001), and in-hospital mortality (p < 0.001) when controlling for age, SAH severity, and other comorbidities. CONCLUSIONS: This study showed significant association between AKI and adverse outcomes in SAH patients, and a correlation between AKI and heightened complication rates, poor functional outcome, extended hospital stays, and elevated mortality rates. Early detection of AKI in SAH patients is vital to enhance their chances of recovery.

Computing contact angles for oil-water-rock systems via thermodynamic integration.

Wettability of rock surfaces with respect to oil and water, which is characterized by the contact angle, is an important factor that determines the efficacy of enhanced oil recovery operations. Experimental determination of contact angles for oil-water-rock systems is expensive and time-consuming due to the extremely long times needed for the establishment of adsorption equilibrium at the liquid-solid interface. Hence, molecular simulations form an attractive tool for computing contact angles. In this work, we use the cleaving wall technique that was developed previously in our group [R. K. R. Addula and S. N. Punnathanam, J. Chem. Phys. 153, 154504 (2020)] to compute solid-liquid interfacial free energy, which is then combined with Young's equation to compute the oil-water contact angle on silica surfaces. The silica surface is modeled with the INTERFACE force field that has been developed to accurately reproduce experimental data. We have considered three different surface chemistries of silica, namely, Q2, Q3, and Q4, in this study. Our calculations reveal that while the Q2 and Q3 surfaces are completely wetted by water, the Q4 surface is partially non-wetted by water. All the simulations needed for this calculation can be performed using the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) molecular package. This should facilitate wider adoption of the Young's equation route to compute contact angles for systems comprised of complex molecules.

A prospective study assessing feasibility of performing percutaneous nephrolithotomy in chronic kidney disease patients - What factors affect the outcome?

OBJECTIVES: To primarily evaluate the functional outcomes of PCNL for bilateral renal calculi/calculi in solitary functioning kidney with Chronic Kidney Disease(CKD). To identify factors affecting the renal replacement therapy following PCNL. MATERIALS AND METHODS: Patients with bilateral renal calculi/calculi in solitary kidney and CKD (eGFR<60/s.creatinine>2) and Good Performance Status [Eastern Cooperative Oncology Group (ECOG): 0-2] were included in the study. RESULTS: A total of 60 patients with CKD who had bilateral renal calculi/calculi in solitary functioning kidney underwent PCNL. At 6 months, eGFR improved or stabilized in 45 (75%) patients, while in 15 (25%) patients eGFR deteriorated. A total of 5 (14.28%) and 2 (25%) patients of CKD stage 4 and 5 respectively had improvement in eGFR as well as CKD stage. Fourteen (82.35%), 21 (60%), 3 (37.5%) patients of CKD stage 3, 4, 5 had improvement in eGFR but not signifi cant enough to cause stage migration. Again 3 (17.65%), 9 ( 40%) and 3 (37.5%) patients of CKD stage 3, 4, 5 had reduction in eGFR but not signifi cant enough to cause stage migration. None of the patients had worsening of CKD stage. Preoperative CKD stage and eGFR were compared with measurements made at the fi nal follow up visit (6 months). CONCLUSION: Our results indicate that most patients of renal calculi with CKD show improvement or stabilization of renal function with aggressive stone removal. Improvement is more in patients who have mild to moderate CKD. Aggressive management of comorbidities, peri-operative UTI and complications may delay or avoid progression of CKD status in such patients.

Inference of Longevity-Related Genes from a Robust Coexpression Network of Seed Maturation Identifies Regulators Linking Seed Storability to Biotic Defense-Related Pathways.

Seed longevity, the maintenance of viability during storage, is a crucial factor for preservation of genetic resources and ensuring proper seedling establishment and high crop yield. We used a systems biology approach to identify key genes regulating the acquisition of longevity during seed maturation of Medicago truncatula. Using 104 transcriptomes from seed developmental time courses obtained in five growth environments, we generated a robust, stable coexpression network (MatNet), thereby capturing the conserved backbone of maturation. Using a trait-based gene significance measure, a coexpression module related to the acquisition of longevity was inferred from MatNet. Comparative analysis of the maturation processes in M. truncatula and Arabidopsis thaliana seeds and mining Arabidopsis interaction databases revealed conserved connectivity for 87% of longevity module nodes between both species. Arabidopsis mutant screening for longevity and maturation phenotypes demonstrated high predictive power of the longevity cross-species network. Overrepresentation analysis of the network nodes indicated biological functions related to defense, light, and auxin. Characterization of defense-related wrky3 and nf-x1-like1 (nfxl1) transcription factor mutants demonstrated that these genes regulate some of the network nodes and exhibit impaired acquisition of longevity during maturation. These data suggest that seed longevity evolved by co-opting existing genetic pathways regulating the activation of defense against pathogens.

The Personal Genome Project Canada: findings from whole genome sequences of the inaugural 56 participants.

BACKGROUND: The Personal Genome Project Canada is a comprehensive public data resource that integrates whole genome sequencing data and health information. We describe genomic variation identified in the initial recruitment cohort of 56 volunteers. METHODS: Volunteers were screened for eligibility and provided informed consent for open data sharing. Using blood DNA, we performed whole genome sequencing and identified all possible classes of DNA variants. A genetic counsellor explained the implication of the results to each participant. RESULTS: Whole genome sequencing of the first 56 participants identified 207 662 805 sequence variants and 27 494 copy number variations. We analyzed a prioritized disease-associated data set (n = 1606 variants) according to standardized guidelines, and interpreted 19 variants in 14 participants (25%) as having obvious health implications. Six of these variants (e.g., in BRCA1 or mosaic loss of an X chromosome) were pathogenic or likely pathogenic. Seven were risk factors for cancer, cardiovascular or neurobehavioural conditions. Four other variants - associated with cancer, cardiac or neurodegenerative phenotypes - remained of uncertain significance because of discrepancies among databases. We also identified a large structural chromosome aberration and a likely pathogenic mitochondrial variant. There were 172 recessive disease alleles (e.g., 5 individuals carried mutations for cystic fibrosis). Pharmacogenomics analyses revealed another 3.9 potentially relevant genotypes per individual. INTERPRETATION: Our analyses identified a spectrum of genetic variants with potential health impact in 25% of participants. When also considering recessive alleles and variants with potential pharmacologic relevance, all 56 participants had medically relevant findings. Although access is mostly limited to research, whole genome sequencing can provide specific and novel information with the potential of major impact for health care.

A Prospective Randomized Clinical Trial of a Novel, Noninvasive Perfusion Enhancement System for the Prevention of Hospital-Acquired Sacral Pressure Injuries.

PURPOSE: The purpose of this study was to determine the effectiveness of a novel, noninvasive perfusion enhancement system versus beds with integrated alternating pressure capabilities for the prevention of hospital-acquired sacral region (sacral, coccygeal, and ischium) pressure injuries in a high-risk, acute care patient population. DESIGN: A prospective randomized trial of high-risk inpatients without preexisting sacral region pressure injuries was conducted. SUBJECTS AND SETTING: The sample comprised 431 randomly enrolled adult patients in a 300-bed tertiary care community teaching hospital. METHODS: Subjects were randomly allocated to one of 2 groups: control and experimental. Both groups received "standard-of-care" pressure injury prevention measures per hospital policy, and both were placed on alternating pressure beds during their hospital stays. In addition, patients in the experimental group used a noninvasive perfusion enhancement system placed on top of their alternating pressure beds and recovery chairs throughout their hospital stay. Fischer's exact probability test was used to compare group differences, and odds ratio (OR) were calculated for comparing pressure injury rates in the experimental and control groups. RESULTS: Three hundred ninety-nine patients completed the trial; 186 patients were allocated to the experimental group and 213 patients to the control group. Eleven patients in the control group versus 2 in the experimental group developed hospital-acquired sacral region pressure injuries (51.6% vs 1.07%; P = .024). Control patients were 5.04 times more likely to develop hospital-acquired sacral region pressure injuries (OR = 0.1996; 95% CI, 0.0437-0.9125). CONCLUSIONS: Patients using a noninvasive perfusion enhancement system developed significantly fewer hospital-acquired sacral pressure injuries than those using an alternating pressure bed without the perfusion enhancement system. These findings suggest that a perfusion enhancement system enhances the success of use of pressure redistributing beds for prevention of hospital-acquired sacral pressure injuries.

Developmental transcriptional profiling reveals key insights into Triticeae reproductive development.

Despite their importance, there remains a paucity of large-scale gene expression-based studies of reproductive development in species belonging to the Triticeae. As a first step to address this deficiency, a gene expression atlas of triticale reproductive development was generated using the 55K Affymetrix GeneChip(®) wheat genome array. The global transcriptional profiles of the anther/pollen, ovary and stigma were analyzed at concurrent developmental stages, and co-expressed as well as preferentially expressed genes were identified. Data analysis revealed both novel and conserved regulatory factors underlying Triticeae floral development and function. This comprehensive resource rests upon detailed gene annotations, and the expression profiles are readily accessible via a web browser.

FISHnet: Detecting chromatin domains in single-cell sequential Oligopaints imaging data.

Sequential Oligopaints DNA FISH is an imaging technique that measures higher-order genome folding at single-allele resolution via multiplexed, probe-based tracing. Currently there is a paucity of algorithms to identify 3D genome features in sequential Oligopaints data. Here, we present FISHnet, a graph theory method based on optimization of network modularity to detect chromatin domains and boundaries in pairwise distance matrices. FISHnet uncovers cell type-specific domain-like folding patterns on single alleles, thus enabling future studies aiming to elucidate the role for single-cell folding variation on genome function.

Caring for sexual and gender minority patients with genitourinary cancer: A primer for inclusive practices.

Recognizing sexual orientation and gender identity (SOGI) is paramount in the management of genitourinary cancers, as sexual and gender minority (SGM) individuals encounter unique healthcare challenges leading to disparities. SGM patients often confront systemic barriers, provider biases, and scarcity of tailored resources, resulting in diminished satisfaction and adverse health outcomes. The evaluation and treatment of genitourinary cancers in SGM patients demand a nuanced, multidisciplinary approach that focuses on the unique health determinants often overlooked by the healthcare system. This review highlights recommendations for the inclusivity of SGM patients within the clinic, from inclusive signage to gender inclusive language. For the evaluation and treatment of SGM patients with genitourinary cancers, it is recommended to employ organ-based language, to utilize validated questionnaires encompassing mental health, sexual behavior, and patient-reported outcomes, and to provide timely referrals to social work and onco-fertility when appropriate. Ultimately, approaching inclusivity through education targeted at both SGM patients and healthcare providers is pivotal for centering care around the patient, improving the quality of life and outcomes for SGM patients facing genitourinary cancers.

Transposon Removal Reveals Their Adaptive Fitness Contribution.

Transposable elements are molecular parasites that persist in their host genome by generating new copies to outpace natural selection. Transposable elements exert a large influence on host genome evolution, in some cases providing adaptive changes. Here we measure the fitness effect of the transposable element insertions in the fission yeast Schizosaccharomyces pombe type strain by removing all insertions of its only native transposable element family, the long terminal repeat retrotransposon Tf2. We show that Tf2 elements provide a positive fitness contribution to its host. Tf2 ablation results in changes to the regulation of a mitochondrial gene and, consistently, the fitness effect are sensitive to growth conditions. We propose that Tf2 influences host fitness in a directed manner by dynamically rewiring the transcriptional response to metabolic stress.

Child Health Needs and the Developmental-Behavioral Pediatrics Workforce Supply: 2020-2040.

Developmental-behavioral pediatrics (DBP) subspecialists care for children with complex neurodevelopmental and behavioral health conditions; additional roles include education and training, advocacy, and research. In 2023, there were 1.0 DBP subspecialists per 100 000 US children aged 0 to 17 years (range 0.0-3.8), with wide variability in DBP subspecialist distribution. Given the prevalence of DB conditions, the current workforce is markedly inadequate to meet the needs of patients and families. The American Board of Pediatrics Foundation led a modeling project to forecast the US pediatric subspecialty workforce from 2020 to 2040 using current trends in each subspecialty. The model predicts workforce supply at baseline and across alternative scenarios and reports results in headcount (HC) and HC adjusted for percent time spent in clinical care, termed "clinical workforce equivalent." For DBP, the baseline model predicts HC growth nationally (+45%, from 669 to 958), but these extremely low numbers translate to minimal patient care impact. Adjusting for population growth over time, projected HC increases from 0.8 to 1.0 and clinical workforce equivalent from 0.5 to 0.6 DBP subspecialists per 100 000 children aged 0 to 18 years by 2040. Even in the best-case scenario (+12.5% in fellows by 2030 and +7% in time in clinical care), the overall numbers would be minimally affected. These current and forecasted trends should be used to shape much-needed solutions in education, training, practice, policy, and workforce research to increase the DBP workforce and improve overall child health.

Mapping geographic disparities in treatment and clinical outcomes of high-grade aneurysmal subarachnoid hemorrhage in the United States.

BACKGROUND AND OBJECTIVE: Although high-grade (Hunt and Hess 4 and 5) aneurysmal subarachnoid hemorrhage (aSAH) typically portends a poor prognosis, early and aggressive treatment has previously been demonstrated to confer a significant survival advantage. This study aims to evaluate geographic, demographic, and socioeconomic determinants of high-grade aSAH treatment in the United States. METHODS: The National Inpatient Sample (NIS) was queried to identify adult high-grade aSAH hospitalizations during the period of 2015 to 2019 using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD) codes. The primary clinical endpoint of this analysis was aneurysm treatment by surgical or endovascular intervention (SEI), while the exposure of interest was geographic region by census division. Favorable functional outcome (assessed by the dichotomous NIS-SAH Outcome Measure, or NIS-SOM) and in-hospital mortality were evaluated as secondary endpoints in treated and conservatively managed groups. RESULTS: Among 99 460 aSAH patients identified, 36 795 (37.0%) were high-grade, and 9210 (25.0%) of these were treated by SEI. Following multivariable logistic regression analysis, determinants of treatment by SEI included female sex (adjusted OR (aOR) 1.42, 95% CI 1.35 to 1.51), transfer admission (aOR 1.18, 95% CI 1.12 to 1.25), private insurance (ref: government-sponsored insurance) (aOR 1.21, 95% CI 1.14 to 1.28), and government hospital ownership (ref: private ownership) (aOR 1.17, 95% CI 1.09 to 1.25), while increasing age (by decade) (aOR 0.93, 95% CI 0.91 to 0.95), increasing mortality risk (aOR 0.60, 95% CI 0.57 to 0.63), urban non-teaching hospital status (aOR 0.66, 95% CI 0.59 to 0.73), rural hospital location (aOR 0.13, 95% CI 0.7 to 0.25), small hospital bedsize (aOR 0.68, 95% CI 0.60 to 0.76), and geographic region (South Atlantic (aOR 0.72, 95% CI 0.63 to 0.83), East South Central (aOR 0.75, 95% CI 0.64 to 0.88), and Mountain (aOR 0.72, 95% CI 0.61 to 0.85)) were associated with a lower likelihood of treatment. High-grade aSAH patients treated by SEI experienced significantly greater rates of favorable functional outcomes (20.1% vs 17.3%; OR 1.20, 95% CI 1.13 to 1.28, P<0.001) and lower rates of mortality (25.8% vs 49.1%; OR 0.36, 95% CI 0.34 to 0.38, P<0.001) in comparison to those conservatively managed. CONCLUSION: A complex interplay of demographic, socioeconomic, and geographic factors influence treatment patterns of high-grade aSAH in the United States.

Post-transcriptional splicing can occur in a slow-moving zone around the gene.

Splicing is the stepwise molecular process by which introns are removed from pre-mRNA and exons are joined together to form mature mRNA sequences. The ordering and spatial distribution of these steps remain controversial, with opposing models suggesting splicing occurs either during or after transcription. We used single-molecule RNA FISH, expansion microscopy, and live-cell imaging to reveal the spatiotemporal distribution of nascent transcripts in mammalian cells. At super-resolution levels, we found that pre-mRNA formed clouds around the transcription site. These clouds indicate the existence of a transcription-site-proximal zone through which RNA move more slowly than in the nucleoplasm. Full-length pre-mRNA undergo continuous splicing as they move through this zone following transcription, suggesting a model in which splicing can occur post-transcriptionally but still within the proximity of the transcription site, thus seeming co-transcriptional by most assays. These results may unify conflicting reports of co-transcriptional versus post-transcriptional splicing.

Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.

We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system. An enrichment analysis revealed previously undescribed plausible candidate CP genes (SMOC1, KDM5B, BCL11A and CYP51A1). A multifactorial CP risk profile and substantial presence of P/LP variants combine to support WGS in the diagnostic work-up across all CP and related phenotypes.

BAR expressolog identification: expression profile similarity ranking of homologous genes in plant species.

Large numbers of sequences are now readily available for many plant species, allowing easy identification of homologous genes. However, orthologous gene identification across multiple species is made difficult by evolutionary events such as whole-genome or segmental duplications. Several developmental atlases of gene expression have been produced in the past couple of years, and it may be possible to use these transcript abundance data to refine ortholog predictions. In this study, clusters of homologous genes between seven plant species - Arabidopsis, soybean, Medicago truncatula, poplar, barley, maize and rice - were identified. Following this, a pipeline to rank homologs within gene clusters by both sequence and expression profile similarity was devised by determining equivalent tissues between species, with the best expression profile match being termed the 'expressolog'. Five electronic fluorescent pictograph (eFP) browsers were produced as part of this effort, to aid in visualization of gene expression data and to complement existing eFP browsers at the Bio-Array Resource (BAR). Within the eFP browser framework, these expression profile similarity rankings were incorporated into an Expressolog Tree Viewer to allow cross-species homolog browsing by both sequence and expression pattern similarity. Global analyses showed that orthologs with the highest sequence similarity do not necessarily exhibit the highest expression pattern similarity. Other orthologs may show different expression patterns, indicating that such genes may require re-annotation or more specific annotation. Ultimately, it is envisaged that this pipeline will aid in improvement of the functional annotation of genes and translational plant research.

Animal assisted therapy in pediatric mental health conditions: A review.

Animal assisted therapy (AAT) has been explored as a treatment option for children with mental health disorders and associated symptoms. AAT can be implemented in inpatient, outpatient, and residential care settings. Some studies demonstrate significant improvement in symptom severity while others report only modest results. In this review, we summarize previous studies that have investigated the applications of AAT for pediatric mental health treatment, focusing on management of symptoms related to post-traumatic stress disorder, depression, anxiety, attention-deficit/hyperactivity disorder, and internet gaming disorder. Current studies on AAT and mental health care tend to lack generalizability due to being single-site studies, and comparisons between studies are difficult because studies tend to adopt different definitions of AAT. Future studies examining the effects of AAT on mental health in general and on symptoms for specific conditions are needed before AAT is widely recommended for the pediatric population.