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Student retention and lack of encouragement are post-secondary institutional barriers that play a critical part in why African Americans are represented in small numbers in science, technology, engineering, and math (STEM) (National Science Foundation, 2017). Historically Black Colleges and Universities (HBCUs) have always promoted a supportive learning atmosphere for African American students. Living learning communities (LLC) were created to improve academic outcomes and to encourage social engagement. The findings of this study suggest that an LLC at an HBCU plays an integral role in sustaining programmatic retention of STEM majors and improving the academic as well as in social outcomes of first-year science and technology students.

PurposeThe FMS-related tyrosine kinase 3 (FLT3) inhibitor gilteritinib is standard therapy for relapsed/refractory FLT3-mutated (FLT3mut) acute myeloid leukemia (AML) but seldom reduces FLT3mut burden or induces sustained efficacy. Gilteritinib combines synergistically with the BCL-2 inhibitor venetoclax in preclinical models of FLT3mut AML.MethodsThis phase Ib open-label, dose-escalation/dose-expansion study (ClinicalTrials.gov identifier: NCT03625505) enrolled patients with FLT3 wild-type and FLT3mut (escalation) or FLT3mut (expansion) relapsed/refractory AML. Patients received 400 mg oral venetoclax once daily and 80 mg or 120 mg oral gilteritinib once daily. The primary objectives were safety, identification of the recommended phase II dose, and the modified composite complete response (mCRc) rate (complete response [CR] + CR with incomplete blood count recovery + CR with incomplete platelet recovery + morphologic leukemia-free state) using ADMIRAL phase III-defined response criteria.ResultsSixty-one patients were enrolled (n = 56 FLT3mut); 64% (n = 36 of 56) of FLT3mut patients had received prior FLT3 inhibitor therapy. The recommended phase II dose was 400 mg venetoclax once daily and 120 mg gilteritinib once daily. The most common grade 3/4 adverse events were cytopenias (n = 49; 80%). Adverse events prompted venetoclax and gilteritinib dose interruptions in 51% and 48%, respectively. The mCRc rate for FLT3mut patients was 75% (CR, 18%; CR with incomplete blood count recovery, 4%; CR with incomplete platelet recovery, 18%; and morphologic leukemia-free state, 36%) and was similar among patients with or without prior FLT3 inhibitor therapy (80% v 67%, respectively). The median follow-up was 17.5 months. The median time to response was 0.9 months, and the median remission duration was 4.9 months (95% CI, 3.4 to 6.6). FLT3 molecular response (< 10-2) was achieved in 60% of evaluable mCRc patients (n = 15 of 25). The median overall survival for FLT3mut patients was 10.0 months.ConclusionThe combination of venetoclax and gilteritinib was associated with high mCRc and FLT3 molecular response rates regardless of prior FLT3 inhibitor exposure. Dose interruptions were needed to mitigate myelosuppression.

BackgroundAnterior cervical discectomy and fusion (ACDF) is a common surgery to treat cervical degenerative disc disease. Use of an anterior spacer and plate system (ASPS) results in increased disc height, higher fusion rate, lower subsidence rate, and lower complication rate than a spacer alone.1,2 However, anterior cervical plating is associated with complications, such as dysphagia, plate-screw dislodgment, soft tissue injury, neural injury, and esophageal perforation.3-9 To potentially reduce these drawbacks, integrated spacer and plate (ISP) systems have gained popularity.MethodsFrom November 2009 to October 2013, a total of 84 consecutive patients who underwent 2-level ACDF using ISP or ASPS were reviewed for clinical and radiographic outcomes. Patient-reported visual analog scale (VAS) and Neck Disability Index (NDI) scores, fusion rates, and hardware failure were determined at 1, 3, 6, 12, and 24 months after surgery.ResultsForty-three patients received ISP and 41 patients received ASPS. There were no significant differences in patient demographics between the 2 groups. Perioperative characteristics were similar, except for operative time. Postoperatively, no significant differences in VAS or NDI scores or fusion status were found. At the proximal surgical level only, there was a trend toward an earlier observed radiographic fusion rate in ASPS vs ISP, but this finding was not statistically significant (P = 0.092). One case of long-term dysphagia was reported in each group. Neither group had implant failures up to 2 years.ConclusionsThe ISP system for 2-level ACDF compared to traditional ASPS has comparable clinical and radiographic outcomes up to 2 years postoperatively. There may be a trend toward an earlier observed radiographic fusion in the ASPS group, but there was no difference in long-term dysphagia rate.Clinical relavanceIntegrated spacer and traditional anterior spacer for 2-level ACDF has similar clinical and radiographical outcome.Level of evidence: 4

Poor sleep quality and low behavioral functioning are commonly reported in children with autism spectrum disorder. This study examined the impact of exercise on sleep on melatonin level and behavioral functioning in the population. Children with autism spectrum disorder (n = 55; age = 10.97 ± 1.90) were randomly allocated to a morning jogging intervention group or a control group. Participants' sleep was measured using actigraphy and sleep log assessments. Twenty-four-hour and first morning urinary 6-sulfatoxymelatonin were used to determine whether the exercise intervention could elicit changes in melatonin levels. Behavioral functioning of the participants was assessed by the repetitive subscale of the Gilliam Autism Rating Scale--3rd edition. All assessments were carried out in baseline, post-intervention, or regular treatment, and follow-up to elucidate the sustainability of the exercise effects. Positive changes were observed between baseline and post-intervention in actigraphy-assessed sleep efficiency and wake after sleep onset, as well as melatonin level and behavioral functioning within the intervention group (ps < 0.017). However, no significant changes were observed in all measurements between post-intervention and follow-up (ps > 0.05). The findings suggest that physical exercise is effective to improve sleep with an increase in melatonin level. It can also reduce repetitive behaviors in children with autism spectrum disorder.

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types.

BackgroundPersistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation.ObjectiveThe goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT.MethodsWe analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature.ResultsRates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates.ConclusionsOur findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.

Extra-curricular activities including clubs, fraternities and societies have been part of the fabric of higher level institutions since their origin. A significant body of educational research has investigated the impact of these activities on academic performance and the acquisition of discipline complementary skills and competencies. In the modern context, driven by forces such as marketization and massification, higher level educational institutions find themselves competing to attract students on the basis of the lived student experience. In this article, a large qualitative survey is used to capture data on the impact of extra-curricular activity on the lived student experience. In addition to supporting existing theories on the academic and skills acquisition effect of extra-curricular activities, the article contributes by identifying a wide range of additionalities to the student experience that participants attribute to their participation in extra-curricular activities.

Syndromic sensorineural hearing loss is multigenic and associated with malformations of the ear and other organ systems. Herein we describe a child admitted to the NIH Undiagnosed Diseases Program with global developmental delay, sensorineural hearing loss, gastrointestinal abnormalities, and absent salivation. Next-generation sequencing revealed a uniparental isodisomy in chromosome 5, and a 22 kb homozygous deletion in SLC12A2, which encodes for sodium, potassium, and chloride transporter in the basolateral membrane of secretory epithelia. Functional studies using patient-derived fibroblasts showed truncated SLC12A2 transcripts and markedly reduced protein abundance when compared with control. Loss of Slc12a2 in mice has been shown to lead to deafness, abnormal neuronal growth and migration, severe gastrointestinal abnormalities, and absent salivation. Together with the described phenotype of the Slc12a2-knockout mouse model, our results suggest that the absence of functional SLC12A2 causes a new genetic syndrome and is crucial for the development of auditory, neurologic, and gastrointestinal tissues.

ObjectiveTourette's syndrome is polygenic and highly heritable. Genome-wide association study (GWAS) approaches are useful for interrogating the genetic architecture and determinants of Tourette's syndrome and other tic disorders. The authors conducted a GWAS meta-analysis and probed aggregated Tourette's syndrome polygenic risk to test whether Tourette's and related tic disorders have an underlying shared genetic etiology and whether Tourette's polygenic risk scores correlate with worst-ever tic severity and may represent a potential predictor of disease severity.MethodsGWAS meta-analysis, gene-based association, and genetic enrichment analyses were conducted in 4,819 Tourette's syndrome case subjects and 9,488 control subjects. Replication of top loci was conducted in an independent population-based sample (706 case subjects, 6,068 control subjects). Relationships between Tourette's polygenic risk scores (PRSs), other tic disorders, ascertainment, and tic severity were examined.ResultsGWAS and gene-based analyses identified one genome-wide significant locus within FLT3 on chromosome 13, rs2504235, although this association was not replicated in the population-based sample. Genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette's syndrome heritability. Tourette's-associated genes were significantly preferentially expressed in dorsolateral prefrontal cortex. Tourette's PRS significantly predicted both Tourette's syndrome and tic spectrum disorders status in the population-based sample. Tourette's PRS also significantly correlated with worst-ever tic severity and was higher in case subjects with a family history of tics than in simplex case subjects.ConclusionsModulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette's syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette's syndrome and other tic disorders in future diagnostic schemata. Tourette's PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity.

Many efforts have been made to enroll more women and other underrepresented groups into STEM fields, including the current NSF-funded S-STEM (S-4) program at our University. S-4 aims to increase enrollment and retention in STEM majors through student activities such as a summer transition to University program, the development of a Learning Community, seminars to expose students to STEM graduate programs and careers, and student support workshops. The S-4 scholarship program is an innovative response to the needs of first generation college students in STEM. While recruitment for this program was more challenging than expected, student retention in the program has exceeded expectation. This study tracked students science identity over the first year in the S-4 program to learn about the types of support that contributed to a science identity and persistence. Scholars were surveyed and interviewed at the end of the summer transition to university program in the first year of our grant, and again at the end of their first year of coursework. In addition to the financial supports, peer collaborations and support groups contributed to the success of students from underrepresented groups. Interviews indicated growth in confidence and STEM identity.

Children with autism spectrum disorder are often reported to have more sleep deficits and poorer sleep quality compared with children with typical development. However, most previous studies have serious methodological limitations, such as varying sample sizes in the comparison groups, wide age range of participants, and body mass index not matched between participants. This study investigated whether sleep patterns differed between children with autism spectrum disorder and those with typical development using a carefully matched case-control design and incorporating both actigraphy and sleep log assessments. A total of 78 children diagnosed with autism spectrum disorder were matched with 78 typical development controls in this study. The matched variables included age, gender, and body mass index. The results showed that children with autism spectrum disorder had shorter sleep duration, reduced sleep efficiency, longer sleep-onset latency, and longer wake after sleep onset than children with typical development (ps < 0.05). Further studies are needed to explore the mechanisms underlying these sleep deficits in children with autism spectrum disorder.

Objective: To compare the effects of the simplified 5-step and the conventional 7-Step hand hygiene programme in a cluster randomized controlled trial among students with intellectual disabilities. Method: A total of 472 Chinese students with intellectual disabilities were randomized to either simplified 5-step or conventional 7-step hand hygiene programme. Assessments included handwashing technique, cleanliness and sick leave days. Results: Handwashing technique scores (g = 0.25, 95% CI [0.18, 0.32]) and hand cleanliness scores (g = 0.33, 95% CI [0.26, 0.4]) in intervention group were significantly higher than those scores in control group at 6th month post-intervention although there were significant increases in the scores within both groups. The mean number of sick leave days decreased between baseline and 10 month in both groups according to descriptive statistics. Conclusions: It is feasible and effective to adopt the simplified 5-step intervention as a standardized handwashing technique for the population group with intellectual disabilities.

There is a scarcity of resources and studies that utilize targeted weight management interventions to engage parents via mHealth tools targeting obese children and adolescents with mild intellectual disabilities (MIDs) extended from school to a home setting. To test the feasibility and acceptability of a school-based weight program (SBWMP) involving parents via mHealth tools designed to reduce weight, enhance knowledge and adopt healthy lifestyles, and thereby achieve better psychosocial well-being among children and adolescents with MIDs. Four special schools were randomly assigned as intervention or control schools. Students from the intervention group (n = 63) were compared to those in the control group (n = 52), which comprised those with usual school planned activities and no parental involvement. Demographics were considered as covariates in a general linear model, an ordinal regression model and a binary logistic regression model analyzing the relationships between the SBWMP and the outcome variables at baseline (T0) and six months later (T1). Body weight, body mass index, and triceps and subscapular skinfold thickness were lower in the intervention group compared to the control group, although the differences were not statistically significant. There was a positive and direct impact of the SBWMP on students' health knowledge and psychological impacts in the intervention group. The SBWMP extended to the home involving parents via mHealth tools is a feasible and acceptable program for this group with MIDs and their parents.

ObjectiveTourette's disorder (TD) and autism spectrum disorder (ASD) share clinical features and possibly an overlapping etiology. The aims of this study were to examine ASD symptom rates in participants with TD, and to characterize the relationships between ASD symptom patterns and TD, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD).MethodParticipants with TD (n = 535) and their family members (n =234) recruited for genetic studies reported TD, OCD, and ADHD symptoms and completed the Social Responsiveness Scale Second Edition (SRS), which was used to characterize ASD symptoms.ResultsSRS scores in participants with TD were similar to those observed in other clinical samples but lower than in ASD samples (mean SRS total raw score = 51; SD = 32.4). More children with TD met cut-off criteria for ASD (22.8%) than adults with TD (8.7%). The elevated rate in children was primarily due to high scores on the SRS Repetitive and Restricted Behaviors (RRB) subscale. Total SRS scores were correlated with TD (r = 0.27), OCD (r = 0.37), and ADHD (r = 0.44) and were higher among individuals with OCD symptom-based phenotypes than for those with tics alone.ConclusionHigher observed rates of ASD among children affected by TD may in part be due to difficulty in discriminating complex tics and OCD symptoms from ASD symptoms. Careful examination of ASD-specific symptom patterns (social communication vs. repetitive behaviors) is essential. Independent of ASD, the SRS may be a useful tool for identifying patients with TD with impairments in social communication that potentially place them at risk for bullying and other negative sequelae.

PurposeWhich infants with brachial plexus birth palsy (BPBP) should undergo microsurgical plexus reconstruction remains controversial. The current gold standard for the decision for plexus reconstruction is serial clinical examinations, but this approach obviates the possibility of early surgical treatment. We hypothesize that a new technique using 3-dimensional volumetric proton density magnetic resonance imaging (MRI) without sedation can evaluate the severity of BPBP injury earlier than serial clinical examinations.MethodsInfants were prospectively enrolled prior to 12 weeks of age and imaged using 3 Tesla MRI without sedation. Clinical scores were collected at all visits. The imaging findings were graded based on the number of injured levels and the severity of each injury, and a radiological score was calculated. All infants were followed at least until the decision for surgery was made based on clinical examination.ResultsNine infants completed the MRI scan and clinical follow-up. The average Toronto score at presentation was 4.4 out of 10 (range, 0-8.2); the average Active Movement Scale score was 50 out of 105 (range, 0-86). Four infants required surgery: 2 because of a flail limb and Horner syndrome and 2 owing to failure to recover antigravity elbow flexion by age 6 months. Radiological scores ranged from 0 to 18 out of a maximum score of 25. The average radiological score for those infants who required surgery was 12 (range, 6.5-18), whereas the average score for infants who did not require surgery was 3.5 (range, 0-8).ConclusionsThree-dimensional proton density MRI can evaluate spinal nerve roots in infants without the need for radiation, contrast agents, or sedation. These data suggest that MRI can help determine the severity of injury earlier than clinical examination in infants with BPBP, although further study of a larger sample of infants with varying severity of disease is necessary.Type of study/level of evidenceDiagnostic II.

ObjectivePhenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts.MethodAssessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated.ResultsThe authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not.ConclusionsThe analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses.