Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation and Maintenance of Behavioral Interventions for 22q11.2 Deletion Syndrome

ABSTRACT 22q11.2-deletion syndrome is a genetic disorder caused by a small deletion of chromosome 22. This deletion often results in developmental delays, learning disabilities, medical conditions, and comorbid psychiatric conditions. Patients with 22q11.2DS may present with a variety of behavioral phenotypes including obsessiveness and rigidity, poor social skills, and anxiety. In some cases, the phenotype can consist of destructive and inappropriate behavior including harming self and others. Behavioral difficulties are reported as one of the most challenging aspects of 22q11.2-deletion syndrome for families of patients, however, few studies have examined behavioral interventions as a possible therapeutic treatment for this population. Using principles derived from operant-behavioral psychology, we conducted functional assessments to determine the environmental correlates of destructive and inappropriate behaviors in two adult men with 22q11.2-deletion syndrome. Subsequently, behavioral interventions based on differential reinforcement were incorporated into each participant’s natural environment to eliminate these behaviors. Significant reductions in destructive and inappropriate behavior were observed with both participants and therapeutic gains were maintained at follow-up. We discuss the role of behavioral interventions in combination with appropriate psychotropic medication when addressing challenging behaviors in this population.
Recurrent bacterial infections, but not fungal infections, 
characterise patients with ELANE‐related neutropenia: a French Severe Chronic Neutropenia Registry study

Among 143 patients with elastase, neutrophil‐expressed (ELANE)‐related neutropenia enrolled in the French Severe Chronic Neutropenia Registry, 94 were classified as having severe chronic neutropenia (SCN) and 49 with cyclic neutropenia (CyN). Their infectious episodes were classified as severe, mild or oral, and analysed according to their natural occurrence without granulocyte‐colony stimulating factor (G‐CSF), on G‐CSF, after myelodysplasia/acute leukaemia or after haematopoietic stem‐cell transplantation. During the disease’s natural history period (without G‐CSF; 1913 person‐years), 302, 957 and 754 severe, mild and oral infectious events, respectively, occurred. Among severe infections, cellulitis (48%) and pneumonia (38%) were the most common. Only 38% of episodes were microbiologically documented. The most frequent pathogens were Staphylococcus aureus (37·4%), Escherichia coli (20%) and Pseudomonas aeruginosa (16%), while fungal infections accounted for 1%. Profound neutropenia (<200/mm3), high lymphocyte count (>3000/mm3) and neutropenia subtype were associated with high risk of infection. Only the p.Gly214Arg variant (5% of the patients) was associated with infections but not the overall genotype. The first year of life was associated with the highest infection risk throughout life. G‐CSF therapy achieved lower ratios of serious or oral infectious event numbers per period but was less protective for patients requiring >10 µg/kg/day. Infections had permanent consequences in 33% of patients, most frequently edentulism.
Long non-coding RNA ZFAS1 alleviates sepsis-induced myocardial injury via target miR-34b-5p/SIRT1

Long non-coding RNA ZFAS1 is down-regulated in sepsis. However, whether ZFAS1 participates in sepsis-induced cardiomyopathy (SIC) remains largely unknown. LPS injection to rats was used to establish an in vivo sepsis model, while LPS stimulation with H9C2 cell was used to mimic an in vitro sepsis-induced myocardial injury model. Western blots and quantitative RT-PCR were performed to evaluate protein and mRNA levels, respectively. ELISA was conducted to determine cytokine levels in supernatant. Flow cytometry was used to test apoptosis. Dual-luciferase assay was performed to validate binding between ZFAS1 and miR-34b-5p, miR-34b-5p and SIRT1. Our data revealed that ZFAS1 and SIRT1 were down-regulated, while miR-34b-5p was up-regulated in LPS-induced H9C2 cells. Inhibition of miR-34b-5p or overexpression of ZFAS1 alleviated inflammatory response and cell apoptosis in LPS-stimulated H9C2 cells. A mechanism study revealed that ZFAS1 sponged miR-34b-5p and thus elevated expression of SIRT1, which was prohibited by miR-34b-5p. ZFAS1 alleviated inflammatory response and cell apoptosis in LPS-stimulated H9C2 cells via the miR-34b-5p/SIRT1 axis, providing novel potential therapeutic targets for SIC.
Comparison between Two Cryo-devices for Vitrification of Immature Oocytes of Indigenous Zebu Cows in Bangladesh

Cryopreservation of oocytes by vitrification technique may contribute a lot in the field of reproductive biotechnology. The objectives of the present study were to evaluate the effectiveness of two cryo-devices for vitrification of immature oocytes of indigenous zebu cows. Slaughter house derived immature cumulus-oocyte-complexes (COCs) of cows were vitrified using 15% dimethyl sulphoxide (DMSO) as cryoprotective agent (CPA) with 0.5 mol sucrose in TCM 199 supplemented with 20% FBS. Vitrification of COCs was completed after immediate plunging of COCs loaded cryotop or French mini straw into the liquid nitrogen (LN2). Then the COCs containing cryotop or French mini straws were warmed in 0.25 mol sucrose and 20% FBS supplemented TCM 199 followed by in vitro culture in 50 μl droplets of bicarbonate buffered TCM 199 supplemented with 10% FBS, pyruvate, FSH and oestradiol for 24 hrs at 39°C with 5% CO2 in humidified air. After maturation culture, oocytes were denuded and examined under inverted microscope for presence of polar body as the indication of maturation. Denuded oocytes were also stained by whole mount technique using 1% orcein to examine the maturation by presence of MII chromosomes. The in vitro maturation rate was significantly (p<0.05) higher in oocytes vitrified and warmed using crytop (47.1±6.9%) than that of French mini straw (15.9±12.5%). Moreover, in vitro maturation rate was significantly (p<0.05) highe r in control oocytes (not vitrified) (84.5±14.2%) than that of vitrified oocytes. In conclusion, cryotop is better than French mini straw as cryo-device for vitrification of bovine immature oocytes
Cytomegalovirus late transcription factor target sequence diversity orchestrates viral early to late transcription

Beta- and gammaherpesviruses late transcription factors (LTFs) target viral promoters containing a TATT sequence to drive transcription after viral DNA replication has begun. Human cytomegalovirus (HCMV), a betaherpesvirus, uses the UL87 LTF to bind both TATT and host RNA polymerase II (Pol II), whereas the UL79 LTF has been suggested to drive productive elongation. Here we apply integrated functional genomics (dTag system, PRO-Seq, ChIP-Seq, and promoter function assays) to uncover the contribution of diversity in LTF target sequences in determining degree and scope to which LTFs drive viral transcription. We characterize the DNA sequence patterns in LTF-responsive and -unresponsive promoter populations, determine where and when Pol II initiates transcription, identify sites of LTF binding genome-wide, and quantify change in nascent transcripts from individual promoters in relation to core promoter sequences, LTF loss, stage of infection, and viral DNA replication. We find that HCMV UL79 and UL87 LTFs function concordantly to initiate transcription from over half of all active viral promoters in late infection, while not appreciably affecting host transcription. Both LTFs act on and bind to viral early-late and late kinetic-class promoters. Over one-third of these core promoters lack the TATT and instead have a TATAT, TGTT, or YRYT. The TATT and non-TATT motifs are part of a sequence block with a sequence code that correlates with promoter transcription level. LTF occupancy of a TATATA palindrome shared by back-to-back promoters is linked to bidirectional transcription. We conclude that diversity in LTF target sequences shapes the LTF-transformative program that drives the viral early-to-late transcription switch.
Comparison of transcriptional responses between pathogenic and nonpathogenic hantavirus infections in Syrian hamsters using NanoString

Background Syrian hamsters infected with Andes virus (ANDV) develop a disease that recapitulates many of the salient features of human hantavirus pulmonary syndrome (HPS), including lethality. Infection of hamsters with Hantaan virus (HTNV) results in an asymptomatic, disseminated infection. In order to explore this dichotomy, we examined the transcriptome of ANDV- and HTNV-infected hamsters. Results Using NanoString technology, we examined kinetic transcriptional responses in whole blood collected from ANDV- and HTNV-infected hamsters. Of the 770 genes analyzed, key differences were noted in the kinetics of type I interferon sensing and signaling responses, complement activation, and apoptosis pathways between ANDV- and HTNV-infected hamsters. Conclusions Delayed activation of type I interferon responses in ANDV-infected hamsters represents a potential mechanism that ANDV uses to subvert host immune responses and enhance disease. This is the first genome-wide analysis of hantavirus-infected hamsters and provides insight into potential avenues for therapeutics to hantavirus disease.
Effect of high variation in transcript expression on identifying differentially expressed genes in RNA‐seq analysis

Great efforts have been made on the algorithms that deal with RNA‐seq data to enhance the accuracy and efficiency of differential expression (DE) analysis. However, no consensus has been reached on the proper threshold values of fold change and adjusted p‐value for filtering differentially expressed genes (DEGs). It is generally believed that the more stringent the filtering threshold, the more reliable the result of a DE analysis. Nevertheless, by analyzing the impact of both adjusted p‐value and fold change thresholds on DE analyses, with RNA‐seq data obtained for three different cancer types from the Cancer Genome Atlas (TCGA) database, we found that, for a given sample size, the reproducibility of DE results became poorer when more stringent thresholds were applied. No matter which threshold level was applied, the overlap rates of DEGs were generally lower for small sample sizes than for large sample sizes. The raw read count analysis demonstrated that the transcript expression of the same gene in different samples, whether in tumor groups or in normal groups, showed high variations, which resulted in a drastic fluctuation in fold change values and adjustedp‐values when different sets of samples were used. Overall, more stringent thresholds did not yield more reliable DEGs due to high variations in transcript expression; the reliability of DEGs obtained with small sample sizes was more susceptible to these variations. Therefore, less stringent thresholds are recommended for screening DEGs. Moreover, large sample sizes should be considered in RNA‐seq experimental designs to reduce the interfering effect of variations in transcript expression on DEG identification.
Meaningfulness among frail older adults receiving home-based care in Finland

Summary Meaningfulness is a fundamental aspect in the promotion of frail older adults’ health and well-being. From a salutogenic point of view, meaningfulness is a vital component of a sense of coherence (SOC), since having a strong SOC aids toward assembling the resources needed to cope with stressors and manage tensions with success. In order to respond to the challenges of population aging and the need to enable frail older adults to live at home for as long as possible, it is important to explore their meaningfulness in the context of home-based care. A salutogenic framework was used to study meaningfulness. The aim was to explore what promotes meaningfulness among frail older adults. The study uses a hermeneutical approach and has a qualitative design. In total, 17 frail older adults were interviewed. The data were analyzed by content analysis. The results uncovered four themes that the respondents considered important in enhancing meaningfulness in daily life: home care personnel, outdoor activities and green spaces, cultural activities and spirituality. Our study revealed the important role of home care personnel as a resource in promoting meaningfulness in the context of home-based care. Hence, this group should be given sufficient resources, knowledge and competence for enabling meaningfulness and thus a SOC amongst frail older adults.
A humanized version of Foxp2 affects ultrasonic vocalization in adult female and male mice

The transcription factor FoxP2 is involved in setting up the neuronal circuitry for vocal learning in mammals and birds and is thought to have played a special role in the evolution of human speech and language. It has been shown that an allele with a humanized version of the murine Foxp2 gene changes the ultrasonic vocalization of mouse pups compared to pups of the wild‐type inbred strain. Here we tested if this humanized allele would also affect the ultrasonic vocalization of adult female and male mice. In a previous study, in which only male vocalization was considered and the mice were recorded under a restricted spatial and temporal regime, no difference in adult vocalization between genotypes was found. Here, we use a different test paradigm in which both female and male vocalizations are recorded in extended social contact. We found differences in temporal, spectral and syntactical parameters between the genotypes in both sexes, and between sexes. Mice carrying the humanized Foxp2 allele were using higher frequencies and more complex syllable types than mice of the corresponding wildtype inbred strain. Our results support the notion that the humanized Foxp2 allele has a differential effect on mouse ultrasonic vocalization. As mice carrying the humanized version of the Foxp2 gene show effects opposite to those of mice carrying disrupted or mutated alleles of this gene, we conclude that this mouse line represents an important model for the study of human speech and language evolution.
The Impact of Transparency and Decision Risk on Human–Automation Teaming Outcomes

Objective Examine the effects of decision risk and automation transparency on the accuracy and timeliness of operator decisions, automation verification rates, and subjective workload. Background Decision aids typically benefit performance, but can provide incorrect advice due to contextual factors, creating the potential for automation disuse or misuse. Decision aids can reduce an operator’s manual problem evaluation, and it can also be strategic for operators to minimize verifying automated advice in order to manage workload. Method Participants assigned the optimal unmanned vehicle to complete missions. A decision aid provided advice but was not always reliable. Two levels of decision aid transparency were manipulated between participants. The risk associated with each decision was manipulated using a financial incentive scheme. Participants could use a calculator to verify automated advice; however, this resulted in a financial penalty. Results For high- compared with low-risk decisions, participants were more likely to reject incorrect automated advice and were more likely to verify automation and reported higher workload. Increased transparency did not lead to more accurate decisions and did not impact workload but decreased automation verification and eliminated the increased decision time associated with high decision risk. Conclusion Increased automation transparency was beneficial in that it decreased automation verification and decreased decision time. The increased workload and automation verification for high-risk missions is not necessarily problematic given the improved automation correct rejection rate. Application The findings have potential application to the design of interfaces to improve human–automation teaming, and for anticipating the impact of decision risk on operator behavior.
No Difference in Reoperation Rates for Adjacent Segment Disease (Operative Adjacent Segment Disease) in Posterior Cervical Fusions Stopping at C7 Versus T1/T2

In a large cohort of 875 patients with posterior cervical fusions ranging from C3 to T1/T2 stopping at -C7 or -T1/T2 with an average follow-up of > 4 years found no statistical difference in reoperation rates for ASD (operative ASD). Study Design. A retrospective cohort study with chart review. Objective. To determine whether there is a difference in reoperation rates for adjacent segment disease ([ASD] operative ASD) in posterior cervical fusions (PCFs) that stop at –C7 versus –T1/T2. Summary of Background Data. There are surgical treatment challenges to the anatomical complexities of the cervicothoracic junction. Current posterior cervical spine surgery is based on the belief that ASD occurs if fusions are stopped at C7 although there is varying evidence to support this assumption. Methods. Patients were followed until validated reoperations for ASD, membership termination, death, or March 31, 2020. Descriptive statistics and 5-year crude incidence rates and 95% confidence intervals for operative ASD for PCF ending at –C7 or –T1/T2 were reported. Time-dependent crude and adjusted multivariable Cox-Proportional Hazards models were used to evaluate operative ASD rates with adjustment for covariates or risk change estimates more than 10%. Results. We identified 875 patients with PCFs (beginning at C3 or C4 or C5 or C6) stopping at either –C7 (n = 470) or –T1/T2 (n = 405) with average follow-up time of 4.6 (±3.3) years and average time to operative ASD of 2.7 (±2.8) years. Crude overall incidence rates for stopping at –C7 (2.12% [1.02%–3.86%]) and –T1/T2 (2.48% [1.25%–4.40%]) were comparable with no statistical difference in risk (adjusted hazard ratio = 1.47, 95% confidence interval = 0.61–3.53, P = 0.39). In addition, we observed no differences in the probability of operative ASD in competing risk time-dependent models (Grey test P = 0.448). Conclusion. A large cohort of 875 patients with PCFs stopping at –C7 or –T1/T2 with an average follow-up of more than 4 years found no statistical difference in reoperation rates for ASD (operative ASD). Level of Evidence: 3
The aesthetic, artistic and creative contributions of dance for health and wellbeing across the lifecourse: a systematic review

ABSTRACT Purpose This review articulates current understanding of the aesthetic, artistic and creative contributions that Dance makes to Health and Wellbeing across the lifecourse within publications 2000–2019, an under-researched area. Methods Review Questions: What are the aesthetic, artistic and creative contributions that Dance makes to Health and Wellbeing across the lifecourse? And what methodologies are appropriate for investigating these contributions? A database keyword search identified 769 articles and 91 evaluations. 109 documents were identified for further in-depth analysis and rating, resulting in 24 papers (11 articles, 3 PhD studies, 10 evaluation reports), which were thematically analysed. Results Findings offer seven interrelated contributions that Dance makes to Health and Wellbeing: embodiment, identity, belonging, self-worth, aesthetics, affective responses and creativity. There was less insight regarding different methodologies, and discussions focused on quantitative data’s limitations. There were insights into inclusion of embodied voices, subjective accounts, and lived experiences. Conclusion Whilst acknowledging challenges, this paper illuminates the key contributions of dance to arts and health. It provides a future conceptual research agenda (prioritizing identity and creativity) and associated methodological developments. It recommends expanding geographical/lifecourse research, better defining terms, fuller epistemological critiques to open space for new methodologies, and continued attendance to appropriate rigour criteria.
Psychological resilience predicting cardiometabolic conditions in adulthood in the Midlife in the United States Study

Significance Experiencing early life adversity may negatively impact mental health; however, many of these individuals display psychological resilience or positive psychological health despite experiences of early adversity. This positive capacity for mental health may extend to physical health benefits, including lower cardiometabolic disease. While research suggests that early adversity increases later disease risk, we found that individuals who display psychological resilience to early adversity did not have higher odds of developing cardiometabolic disease. Indeed, those who showed psychological resilience had similar odds of disease to peers who did not experience early adversity. These findings were also reflected in measures of biological cardiometabolic risk. Overall, findings suggest that individuals who manifest psychological resilience may have lower cardiometabolic disease risk later in life. Early adversity is associated with poor cardiometabolic health, potentially via psychological distress. However, not everyone exposed to adversity develops significant distress. Psychological resilience and positive psychological health despite adversity may protect against unfavorable cardiometabolic outcomes that are otherwise more likely. We examined early adversity, psychological resilience, and cardiometabolic risk among 3,254 adults in the Midlife in the United States Study. Psychological resilience was defined according to both early psychosocial adversity and adult psychological health (characterized by low distress and high wellbeing) at Wave 1 (1994 to 1995). Categorical resilience was derived by cross-classifying adversity (exposed versus unexposed) and psychological health (higher versus lower). We also assessed count of adversities experienced and psychological symptoms as separate variables. Incident cardiometabolic conditions (e.g., heart attack, stroke, and diabetes) were self-reported at Waves 2 (2004 to 2005) and 3 (2013 to 2014). Secondary analyses examined biological cardiometabolic risk using a composite of biomarkers available within a Wave-2 subsample. Logistic and Poisson regressions evaluated associations of resilience with cardiometabolic health across 20 follow-up y, adjusting for relevant covariates. In this initially healthy sample, nonresilient (adversity-exposed, lower psychological health) versus resilient (adversity-exposed, high psychological health) individuals had 43% higher odds of cardiometabolic conditions (95% CI 1.10 to 1.85). Odds of cardiometabolic conditions were similar among resilient versus unexposed, psychologically healthy individuals. More adversity experiences were associated with increased odds, while better psychological health with decreased odds of cardiometabolic conditions, and effects were largely independent. Patterns were similar for objectively assessed cardiometabolic risk. Psychological resilience in midlife may protect against negative cardiometabolic impacts of early adversity.