Miracle-dz/UniFAR-FTUs huggingface dataset:
Residential Immersive Life Skills Programs: A Catalyst for Facilitating Emotional Literacy Development for Youth with Disabilities

ABSTRACT Statement of Purpose Residential Immersive life skills (RILS) programs are unique programs for youth with disabilities. These programs enable youth to develop adaptive behaviors required to navigate adulthood. This study explored the emergence of emotional literacy development for youth who attended RILS programs. Methods This study draws on twenty-five qualitative interviews that were conducted with nine youth who attended RILS programs. Data were analyzed using thematic analysis, aligned to a phenomenological approach. Results The themes reflecting emotional literacy development in youth were: (1) Enhanced intrapersonal development; (2) Shifts in emotional regulation and emotional responses; (3) Realized potential and self-actualization. Conclusions The opportunities and experiences offered in the RILS programs have the potential to facilitate emotional literacy development in youth with disabilities. The findings contribute towards the research evidence on the importance of emotional literacy development in young people with disabilities and the development and mobilization of evidence-based life skills programs.
Curriculum for endoscopic submucosal dissection training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement

Main Recommendation There is a need for well-organized comprehensive strategies to achieve good training in ESD. In this context, the European Society of Gastrointestinal Endoscopy (ESGE) have developed a European core curriculum for ESD practice across Europe with the aim of high quality ESD training. Advanced endoscopy diagnostic practice is advised before initiating ESD training. Proficiency in endoscopic mucosal resection (EMR) and adverse event management is recommended before starting ESD training ESGE discourages the starting of initial ESD training in humans. Practice on animal and/or ex vivo models is useful to gain the basic ESD skills. ESGE recommends performing at least 20 ESD procedures in these models before human practice, with the goal of at least eight en bloc complete resections in the last 10 training cases, with no perforation. ESGE recommends observation of experts performing ESD in tertiary referral centers. Performance of ESD in humans should start on carefully selected lesions, ideally small ( < 30 mm), located in the antrum or in the rectum for the first 20 procedures. Beginning human practice in the colon is not recommended. ESGE recommends that at least the first 10 human ESD procedures should be done under the supervision of an ESD-proficient endoscopist. Endoscopists performing ESD should be able to correctly estimate the probability of performing a curative resection based on the characteristics of the lesion and should know the benefit/risk relationship of ESD when compared with other therapeutic alternatives. Endoscopists performing ESD should know how to interpret the histopathology findings of the ESD specimen, namely the criteria for low risk resection (“curative”), local risk resection, and high risk resection (“non-curative”), as well as their implications. ESD should be performed only in a setting where early and delayed complications can be managed adequately, namely with the possibility of admitting patients to a ward, and access to appropriate emergency surgical teams for the organ being treated with ESD.
Effect of Intermittent Versus Continuous Low-Dose Aspirin on Nasal Epithelium Gene Expression in Current Smokers: A Randomized, Double-Blinded Trial

A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blinded study in current heavy smokers to compare modulating effects of intermittent versus continuous low-dose ASA on nasal epithelium gene expression and arachidonic acid (ARA) metabolism. Fifty-four participants were randomized to intermittent (ASA 81 mg daily for one week/placebo for one week) or continuous (ASA 81 mg daily) for 12 weeks. Low-dose ASA suppressed urinary prostaglandin E2 metabolite (PGEM; change of −4.55 ± 11.52 from baseline 15.44 ± 13.79 ng/mg creatinine for arms combined, P = 0.02), a surrogate of COX-mediated ARA metabolism, but had minimal effects on nasal gene expression of nasal or bronchial gene-expression signatures associated with smoking, lung cancer, and chronic obstructive pulmonary disease. Suppression of urinary PGEM correlated with favorable changes in a smoking-associated gene signature (P < 0.01). Gene set enrichment analysis (GSEA) showed that ASA intervention led to 1,079 enriched gene sets from the Canonical Pathways within the Molecular Signatures Database. In conclusion, low-dose ASA had minimal effects on known carcinogenesis gene signatures in nasal epithelium of current smokers but results in wide-ranging genomic changes in the nasal epithelium, demonstrating utility of nasal brushings as a surrogate to measure gene-expression responses to chemoprevention. PGEM may serve as a marker for smoking-associated gene-expression changes and systemic inflammation. Future studies should focus on NSAIDs or agent combinations with broader inhibition of pro-inflammatory ARA metabolism to shift gene signatures in an anti-carcinogenic direction.
Sequencing‐based microsatellite instability testing using as few as six markers for high‐throughput clinical diagnostics

Microsatellite instability (MSI) testing of colorectal cancers (CRCs) is used to screen for Lynch syndrome (LS), a hereditary cancer‐predisposition, and can be used to predict response to immunotherapy. Here, we present a single‐molecule molecular inversion probe and sequencing‐based MSI assay and demonstrate its clinical validity according to existing guidelines. We amplified 24 microsatellites in multiplex and trained a classifier using 98 CRCs, which accommodates marker specific sensitivities to MSI. Sample classification achieved 100% concordance with the MSI Analysis System v1.2 (Promega) in three independent cohorts, totaling 220 CRCs. Backward–forward stepwise selection was used to identify a 6‐marker subset of equal accuracy to the 24‐marker panel. Assessment of assay detection limits showed that the 24‐marker panel is marginally more robust to sample variables than the 6‐marker subset, detecting as little as 3% high levels of MSI DNA in sample mixtures, and requiring a minimum of 10 template molecules to be sequenced per marker for >95% accuracy. BRAF c.1799 mutation analysis was also included to streamline LS testing, with all c.1799T>A variants being correctly identified. The assay, therefore, provides a cheap, robust, automatable, and scalable MSI test with internal quality controls, suitable for clinical cancer diagnostics.
Correlation between CT based radiomics features and gene expression data in non-small cell lung cancer.

OBJECTIVE Radiogenomics investigates radiographic imaging phenotypes associated with gene expression patterns. This study aims to explore relationships between CT imaging radiomics features and gene expression data in non-small cell lung cancer (NSCLC). METHODS Eighty-nine NSCLC patients are included in the study. Radiomics features are extracted and selected to quantify the phenotype of tumors on CT-scans. Co-expressed genes are also clustered and the first principal component of the cluster is represented, which is defined as a metagene. Then, statistical analysis was performed to assess association of CT radiomics features with metagenes. In addition, predictive models are built and metagene enrichment are conducted to further evaluate performance of NSCLC radiogenomics statistically and biologically. RESULTS There are 187 significant pairwise correlations between a CT radiomics feature and a metagene of NSCLC, where eighteen metagenes are annotated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. Metagenes are predicted in terms of radiomics features with an accuracy of 41.89% -89.93%. CONCLUSIONS This study reveals the associations between CT imaging radiomics features and NSCLC co-expressed gene sets. The findings suggest that CT radiomics features can reflect important biological information of NSCLC patients, which may have a significant clinical impact as CT is routinely used in clinical practice, assisting in improving medical decision-support at low cost.
Tumor mutational burden assessed by targeted NGS predicts clinical benefit from immune checkpoint inhibitors in non‐small cell lung cancer

In non‐small cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs) significantly improve overall survival (OS). Tumor mutational burden (TMB) has emerged as a predictive biomarker for patients treated with ICIs. Here, we evaluated the predictive power of TMB measured by the Oncomine™ Tumor Mutational Load targeted sequencing assay in 76 NSCLC patients treated with ICIs. TMB was assessed retrospectively in 76 NSCLC patients receiving ICI therapy. Clinical data (RECIST 1.1) were collected and patients were classified as having either durable clinical benefit (DCB) or no durable benefit (NDB). Additionally, genetic alterations and PD‐L1 expression were assessed and compared with TMB and response rate. TMB was significantly higher in patients with DCB than in patients with NDB (median TMB = 8.5 versus 6.0 mutations/Mb, Mann–Whitney p = 0.0244). 64% of patients with high TMB (cut‐off = third tertile, TMB ≥ 9) were responders (DCB) compared to 33% and 29% of patients with intermediate and low TMB, respectively (cut‐off = second and first tertile, TMB = 5–9 and TMB ≤ 4, respectively). TMB‐high patients showed significantly longer progression‐free survival (PFS) and OS (log‐rank test p = 0.0014 for PFS and 0.0197 for OS). While identifying different subgroups of patients, combining PD‐L1 expression and TMB increased the predictive power (from AUC 0.63 to AUC 0.65). Our results show that the TML panel is an effective tool to stratify patients for ICI treatment. A combination of biomarkers might maximize the predictive precision for patient stratification. Our study supports TMB evaluation through targeted NGS in NSCLC patient samples as a tool to predict response to ICI therapy. We offer recommendations for a reliable and cost‐effective assessment of TMB in a routine diagnostic setting. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Mice Lacking the Intestinal and Renal Neutral Amino Acid Transporter SLC6A19 Demonstrate the Relationship between Dietary Protein Intake and Amino Acid Malabsorption

Dietary protein restriction has beneficial impacts on metabolic health. B0AT1 (SLC6A19) is the major transporter of neutral amino acids at the intestinal epithelia and absorbs the bulk of the diet-derived neutral amino acids from the intestinal lumen. It also reabsorbs neutral amino acids in the renal proximal tubules. Mice lacking B0AT1 show cellular outcomes of protein restriction, such as high FGF21 levels and low mTORC1 activity. Moreover, they have improved glucose homeostasis and resist diet-induced obesity. In this study, we investigated the relationship between protein restriction and dietary protein intake in C57Bl6/J wild-type (wt) and SLC6A19-knockout (SLC6A19ko) mice. When SLC6A19ko mice were fed diets containing 5%, 25%, or 52% of their total calories derived from protein, no differences in food intake or weight gain were observed. All essential amino acids significantly positively correlated with increasing dietary casein content in the wt mice. The SLC6A19ko mice showed reduced postprandial levels of essential amino acids in plasma, particularly following high-protein diets. Upon fasting, essential amino acids were the same in the wt and SLC6A19ko mice due to reduced amino acid catabolism. Bacterial metabolites originating from amino acid fermentation correlated with the dietary protein content, but showed a complex profile in the blood of the SLC6A19ko mice. This study highlights the potential of SLC6A19 as a knock-out or inhibition target to induce protein restriction for the treatment of metabolic disorders.
Therapeutic genome editing of triple-negative breast tumors using a noncationic and deformable nanolipogel

Significance Triple-negative breast cancer (TNBC), which represents 12% of all breast cancers, is a devastating breast cancer subtype that occurs more frequently in women under 50 y of age, in African American women, and in individuals carrying a BRCA1 gene mutation. Because of the lack of therapeutic targets and limited treatment options, the prognosis for patients with TNBC remains the poorest of all patients with breast cancer. Here we report the synthesis and application of a novel CRISPR nanotherapeutic to effectively knock out Lipocalin 2 (Lcn2), a breast cancer-promoting gene, in TNBC tumors via in vivo genome editing, leading to a significant suppression of TNBC tumor growth. Our studies demonstrate that CRISPR genome editing is a promising targeted gene therapy approach for TNBC. Triple-negative breast cancer (TNBC), which has the highest mortality rate of all breast cancer, is in urgent need of a therapeutic that hinders the spread and growth of cancer cells. CRISPR genome editing holds the promise of a potential cure for many genetic diseases, including TNBC; however, its clinical translation is being challenged by the lack of safe and effective nonviral delivery systems for in vivo therapeutic genome editing. Here we report the synthesis and application of a noncationic, deformable, and tumor-targeted nanolipogel system (tNLG) for CRISPR genome editing in TNBC tumors. We have demonstrated that tNLGs mediate a potent CRISPR knockout of Lipocalin 2 (Lcn2), a known breast cancer oncogene, in human TNBC cells in vitro and in vivo. The loss of Lcn2 significantly inhibits the migration and the mesenchymal phenotype of human TNBC cells and subsequently attenuates TNBC aggressiveness. In an orthotopic TNBC model, we have shown that systemically administered tNLGs mediated >81% CRISPR knockout of Lcn2 in TNBC tumor tissues, resulting in significant tumor growth suppression (>77%). Our proof-of-principle results provide experimental evidence that tNLGs can be used as a safe, precise, and effective delivery approach for in vivo CRISPR genome editing in TNBC.
Single housing‐induced effects on cognitive impairment and depression‐like behavior in male and female mice involve neuroplasticity‐related signaling

Single‐housed stress elicits a range of social isolation‐related behavioral and neurobiological abnormalities. To investigate single housing‐induced behavioral changes and sex differences on stress outcomes, we examined single‐housed stress‐induced learning and memory impairment, depression‐like behaviors, neuroplasticity abnormalities and underlying mechanism. The results showed that male and female mice socially isolated for 8 weeks had significantly decreased memory acquisition, as demonstrated in the learning curve of the Morris water maze task. Memory consolidation and retrieval were also decreased in both the single‐housed male and female mice. These findings were corroborated further by the two classical animal models, Y‐maze and novel object recognition tests, as demonstrated by reduced spontaneous alternation and recognition index in both sexes of single‐housed mice. Subsequent studies suggested that single‐housed male mice exhibited increased immobility time in both the forced swim and tail suspension tests, while the female mice only exhibited increased immobility time in the tail suspension test. Moreover, single‐housed stress significantly decreased the apical and basal branch points, dendritic length, and spine density in the CA1 of hippocampal neurons in both male and female mice. These effects were consistent with decreased neuroplasticity and neuroprotective‐related molecules such as synaptophysin, PSD95, PKA, pCREB and BDNF expression. These findings suggest that loss of neuronal remodeling and neuroprotective mechanisms due to single housing are involved in behavioral changes in both male and female mice. The results provide further evidence that neuroplasticity‐related signaling plays a crucial role in isolation‐induced effects on neuropsychiatric behavioral deficits in both sexes.
Postnatal clinical phenotype of five patients with Pallister–Killian Syndrome (tetrasomy 12p): Interest of array CGH for diagnosis and review of the literature

Pallister–Killian syndrome (PKS) is a rare sporadic disorder caused by tetrasomy of the short arm of chromosome 12. The main clinical manifestations are global developmental delay, intellectual disability, epilepsy, dysmorphic features, hypopigmented and/or hyperpigmented lesions, and multiple congenital anomalies. PKS is associated with tissue mosaicism, which is difficult to diagnose through peripheral blood sample by conventional cytogenetic methods and fluorescence in situ hybridization.
Seasonal Accumulated Workloads in Collegiate Men's Soccer: A Comparison of Starters and Reserves

Abstract Curtis, RM, Huggins, RA, Benjamin, CL, Sekiguchi, Y, Arent, S, Armwald, B, Pullara, JM, West, CA, and Casa, DJ. Seasonal accumulated workloads in collegiate men's soccer: a comparison of starters and reserves. J Strength Cond Res 35(11): 3184–3189, 2021—The purpose of this investigation was to quantify and compare player's season total-, match-, and training-accumulated workload by player status characteristics (i.e., starter vs. reserve) in American collegiate men's soccer. Global positioning system (GPS) and heart rate (HR)-derived workloads were analyzed from 82 collegiate male soccer athletes from 5 separate teams over the 2016 and 2017 seasons. Differences in total physical and physiological workloads (i.e., total distance, accelerations, and weighted HR-zone training impulse [TRIMP] score) as well as workloads over a range of intensity zones were examined using multilevel mixed models, with mean difference (MD) and effect size (ES) reported. Starters accumulated substantially more total distance (MD = 82 km, ES = 1.23), TRIMP (MD = 2,210 au, ES = 0.63), and total accelerations (MD = 6,324 n, ES = 0.66) over the season. Total accumulated distance in all velocity zones (ES [range] = 0.87–1.08), all accelerations zones (ES [range] = 0.54–0.74), and time spent at 70–90% HRmax (ES [range] = 0.60–1.12) was also greater for starters. Reserves accumulated substantially more total distance (MD = 20 km, ES = 0.43) and TRIMP (MD = 1,683 au, ES = 0.79) during training. Although reserves show elevated physical and physiological loads during training compared with starters, there is an imbalance in overall workloads between player roles, with starters incurring substantially more match and total seasonal workloads. These results indicate managing player workloads in soccer requires attention to potential imbalances between players receiving variable match times. Coaches and practitioners in collegiate men's soccer may consider implementing strategies to reduce discrepancies in loading between starters and reserves. Individualized monitoring of training and match workloads may assist in the implementation of more balanced load management programs.
Investigating the Factors Influencing Students ’ Acceptance of Mobile Learning : The Cave Hill Campus Experience

The unprecedented growth in the mobile computing market is creating opportunities within the higher education sector. However, before merging these new technologies with traditional methods, it is critical that the factors that are likely to affect the success of m-learning initiatives be identified. This study uses the Unified Theory of Acceptance and Use of Technology (UTAUT) model to determine the critical factors influencing undergraduate students’ acceptance of m-learning technologies. Six hundred undergraduates at the Cave Hill Campus of the University of the West Indies in Barbados participated in the study. The data were analysed using multiple linear regression to determine the effect of four UTAUT constructs on behavioural intentions, moderated by age and gender. The findings revealed that whereas the factors performance expectancy, effort expectancy, and facilitating conditions were significant, positive, determinants of students’ intentions to adopt m-learning technologies, social influence had no significant effect in this Caribbean context. This study should be of interest to higher institutions desirous of introducing m-learning initiatives, particularly in developing countries.
Stimulation-induced side effects after deep brain stimulation – a systematic review

Abstract Objective: Deep brain stimulation (DBS) was approved by Food and Drug Administration for Parkinson’s disease, essential tremor, primary generalised or segmental dystonia and obsessive-compulsive disorder (OCD) treatment. The exact mechanism of DBS remains unclear which causes side effects. The aim of this review was to assess variables causing stimulation-induced chronic psychiatric/personality-changing side effects. Methods: The analysis of scientific database (PubMed, Cochrane Library, EMBASE) was conducted. The included articles had to be research study or case report and DBS to be conducted in therapeutic purposes. The researches with mental disorders in patients’ medical histories were excluded. Results: Seventeen articles were used in the review. In the group of movement disorders the characteristic of side effects was strongly related to the placement of the electrode implantation. Tiredness/fatigue was correlated with DBS in thalamus. Implantations in subthalamic nucleus were mostly followed by affective side effects such as depression or suicide. The higher voltage of electrode was connected with more severe depression after implantation. The analysis of affective disorder contained only three articles – two about OCD and one about depression. Forgetfulness and word-finding problems as activities connected with cognition may be an inevitable side effect if obsessive thoughts are to be inhibited. Conclusion: DBS of subthalamic nucleus should be seen as the most hazardous place of implantation. As a result there is a strong need of ‘gold standards’ based on the connectivity research and closer cooperation of scientists and clinicians.