Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting lithium treatment response in bipolar patients using gender-specific gene expression biomarkers and machine learning [version 1; peer review: 1 approved with reservations]

Background: We sought to test the hypothesis that transcriptiome-level genes signatures are differentially expressed between male and female bipolar patients, prior to lithium treatment, in a patient cohort who later were clinically classified as lithium treatment responders. Methods: Gene expression study data was obtained from the Lithium Treatment-Moderate dose Use Study data accessed from the National Center for Biotechnology Information’s Gene Expression Omnibus via accession number GSE4548. Differential gene expression analysis was conducted using the Linear Models for Microarray and RNA-Seq (limma) package and the Random Forests machine learning algorithm in R. Results: In pre-treatment lithium responders, the following genes were found having a greater than 0.5 fold-change, and differentially expressed indicating a male bias: RBPMS2, SIDT2, CDH23, LILRA5, and KIR2DS5; while the female-biased genes were: HLA-H, RPS23, FHL3, RPL10A, NBPF14, PSTPIP2, FAM117B, CHST7, and ABRACL. Conclusions: Using machine learning, we developed a pre-treatment gender-and gene-expression-based predictive model selective for lithium responders with an ROC AUC of 0.92 for men and an ROC AUC of 1 for women.
Cytomegalovirus in solid organ transplant recipients—Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice

Cytomegalovirus (CMV) is one of the most common opportunistic infections that affect the outcome of solid organ transplantation. This updated guideline from the American Society of Transplantation Infectious Diseases Community of Practice provides evidence‐based and expert recommendations for screening, diagnosis, prevention, and treatment of CMV in solid organ transplant recipients. CMV serology to detect immunoglobulin G remains as the standard method for pretransplant screening of donors and transplant candidates. Antiviral prophylaxis and preemptive therapy are the mainstays of CMV prevention. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is highlighted, as a result of variability of CMV nucleic acid testing, even in the contemporary era when calibrators are standardized. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management. Strategies for managing drug‐resistant CMV infection are presented. There is an increasing use of CMV‐specific cell‐mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, but their role in optimizing CMV prevention and treatment efforts has yet to be demonstrated. Specific issues related to pediatric transplant recipients are discussed.
The impact of service user’s suicide on mental health professionals

Objectives Our principle objective was to examine the personal and professional impact of service user (SU) suicide on mental health professionals (MHPs). We also wished to explore putative demographic or clinical factors relating to SUs or MPHs that could influence the impact of SU suicide for MHPs and explore factors MHPs report as helpful in reducing distress following SU suicide. Methods A mixed-method questionnaire with quantitative and thematic analysis was utilised. Results Quantitative data indicated SU suicide was associated with personal and professional distress with sadness (79.5%), shock (74.5%) and surprise (68.7%) particularly evident with these phenomena lasting less than a year for more than 90% of MHPs. MHPs also reported guilt, reduced self-confidence and a fear of negative publicity. Thematic analysis indicated that some MHPs had greater expertise when addressing SU suicidal ideation and in supporting colleagues after experiencing a SU suicide. Only 17.7% of MHPs were offered formal support following SU suicide. Conclusion SU suicide impacts MHPs personally and professionally in both a positive and negative fashion. A culture and clear pathway of formal support for MHPs to ascertain the most appropriate individualised support dependent on the distress they experience following SU suicide would be optimal.
Urea Cycle Sustains Cellular Energetics upon EGFR Inhibition in EGFR-Mutant NSCLC

Mutations in oncogenes and tumor suppressor genes engender unique metabolic phenotypes crucial to the survival of tumor cells. EGFR signaling has been linked to the rewiring of tumor metabolism in non–small cell lung cancer (NSCLC). We have integrated the use of a functional genomics screen and metabolomics to identify metabolic vulnerabilities induced by EGFR inhibition. These studies reveal that following EGFR inhibition, EGFR-driven NSCLC cells become dependent on the urea cycle and, in particular, the urea cycle enzyme CPS1. Combining knockdown of CPS1 with EGFR inhibition further reduces cell proliferation and impedes cell-cycle progression. Profiling of the metabolome demonstrates that suppression of CPS1 potentiates the effects of EGFR inhibition on central carbon metabolism, pyrimidine biosynthesis, and arginine metabolism, coinciding with reduced glycolysis and mitochondrial respiration. We show that EGFR inhibition and CPS1 knockdown lead to a decrease in arginine levels and pyrimidine derivatives, and the addition of exogenous pyrimidines partially rescues the impairment in cell growth. Finally, we show that high expression of CPS1 in lung adenocarcinomas correlated with worse patient prognosis in publicly available databases. These data collectively reveal that NSCLC cells have a greater dependency on the urea cycle to sustain central carbon metabolism, pyrimidine biosynthesis, and arginine metabolism to meet cellular energetics upon inhibition of EGFR. Implications: Our results reveal that the urea cycle may be a novel metabolic vulnerability in the context of EGFR inhibition, providing an opportunity to develop rational combination therapies with EGFR inhibitors for the treatment of EGFR-driven NSCLC.
A case report of high-grade astroblastoma in a young adult

Astroblastoma is an uncommon neuroepithelial primary tumor of the brain which is of uncertain origin. We present a case of high-grade astroblastoma in an 18-year-old female with a severe headache, loss of appetite, vomiting and generalized weakness. The patient had undergone a right frontoparietal craniotomy. Large subfalcine meningioma was excised. The lesion was suspected to be a meningioma. Primary radiological investigation revealed a 6.8 cm × 5.8 cm × 5.4 cm lesion. Although the radiological and intraoperative findings were of an extra-axial tumor, the histology and immunophenotype was of an astroblastoma. The patient was treated with cyclophosphamide, cisplatin and etoposide chemotherapy regimen. The patient was later treated with bi-weekly bevacizumab. The patient had improved symptomatically post-chemotherapy. However, there was no significant difference in lesion size. The patient died after 2 weeks. The prognosis of patients with astroblastoma is extremely poor as observed in our case.
Pretreatment with P2Y12 receptor antagonists in ST-elevation myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry

AIMS Pretreatment of patients with ST-elevation myocardial infarction (STEMI) with P2Y12 receptor antagonists is supported by guidelines and is a common practice despite the lack of definite evidence for its benefit. METHODS AND RESULTS Using data from the Swedish Coronary Angiography and Angioplasty Registry on procedures between 2005 and 2016, we stratified all patients who underwent primary percutaneous coronary intervention due to STEMI in Sweden by whether or not they were pretreated with P2Y12 receptor antagonists. We investigated associations between pretreatment with P2Y12 receptor antagonists and the risk of adverse outcomes using propensity score-adjusted mixed-effects logistic regression, which accounted for clustering of patients within hospitals. The primary endpoint was all-cause death within 30 days. Secondary endpoints were infarct-related artery (IRA) occlusion, 30-day stent thrombosis, in-hospital bleeding, neurological complications, and cardiogenic shock. In total, 44 804 patients were included. They were treated with clopidogrel (N = 26 136, 58.3%), ticagrelor (N = 15 792, 35.3%), or prasugrel (N = 2352, 5.3%); 37 840 (84.5%) were pretreated, and 30 387 (67.8%) had IRA occlusion. At 30 days, there were 2488 (5.6%) deaths and 267 (0.6%) stent thrombosis. Pretreatment was not associated with better survival at 30 days [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.95-1.24; P = 0.313], reduced IRA occlusion (OR 0.98, 95% CI 0.92-1.05; P = 0.608), decreased stent thrombosis (OR 0.99, 95% CI 0.69-1.43; P = 0.932), higher risk of in-hospital bleeding (OR 1.05, 95% CI 0.89-1.26; P = 0.526), or neurological complications (OR 0.72, 95% CI 0.43-1.21; P = 0.210). CONCLUSION Pretreatment of STEMI patients with P2Y12 receptor antagonists was not associated with improved clinical outcomes.
Immunophenotypic Features of Myeloid Neoplasms Associated with Chromosome 7 Abnormalities

Abnormalities involving chromosome 7 are one of the most frequent chromosomal aberrations in myeloid neoplasms including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) and are associated with an adverse prognosis. Immunophenotyping by flow cytometry provides data that can assist in the diagnosis and classification of myeloid neoplasms. The immunophenotypic features of myeloid neoplasms with monosomy 7 or del(7q) have not been previously described in a comprehensive fashion.
How do participant experiences and characteristics influence engagement in exercise referral? A qualitative longitudinal study of a scheme in Northumberland, UK

Objectives Exercise referral schemes (ERSs) are internationally widespread. This study aimed to gain an insight into differential engagement through understanding participant experiences of patients referred by healthcare professionals to one such scheme in the UK. Design The study employed a qualitative longitudinal approach using semistructured interviews, with results reported using Consolidated criteria for Reporting Qualitative research guidelines. Setting Two leisure centres providing an ‘emerging best-practice’ ERS in northeast England. Participants Referred patients (n=11), who had not yet commenced the scheme, were recruited on a voluntary basis. Seven females and four males, with a range of non-communicable diseases, such as cardiovascular disease, mental health issues, diabetes, overweight/obesity and musculoskeletal problems, participated. Intervention 24-weeks, two times per week, of supervised exercise sessions and three one-to-one assessments (prescheme, 12 weeks and 24 weeks) for patients referred from primary and secondary care. Primary outcome measures Two longitudinal semistructured interviews, prior to commencement and 12–20 weeks later, were thematically analysed using the framework approach. Analysis comprised seven stages: transcription, familiarisation, coding, development and application of an analytical framework, charting data using a matrix and interpretation of data. Interpretation went beyond descriptions of individual cases to develop themes, which identified and offered possible explanations for differing participant experiences. Results Three overarching themes emerged. First, ‘success’, with engaged participants focused on health outcomes and reported increases in physical activity. Second, ‘struggle’, with short-term success but concerns regarding continued engagement. Participants reported scheme dependency and cyclical needs. Finally, ‘defeat’, where ill health, social anxiety and/or poor participation experience made engagement difficult. Conclusion Some success in engaging those with non-communicable diseases was reported, resulting in positive effects on health and well-being. The study highlights complexity within ERSs and inequality of access for those with challenging health and social circumstances. Improved, or different, behaviour change support is required for referrals finding engagement difficult.
High incidence of injuries at the Pyeongchang 2018 Paralympic Winter Games: a prospective cohort study of 6804 athlete days

Objective To describe the epidemiology of sports injury at the Pyeongchang 2018 Paralympic Winter Games. Methods 567 athletes from 49 countries were monitored daily for 12 days over the Pyeongchang 2018 Paralympic Winter Games (6804 athlete days). Injury data were obtained daily from teams with their own medical support (41 teams and 557 athletes) and teams without their own medical support (8 teams and 10 athletes) through two electronic data capturing systems. Results 112 of 567 athletes (19.8%) reported a total of 142 injuries, with an injury incidence rate (IR) of 20.9 per 1000 athlete days (95% CI 17.4 to 25.0). The highest IR was reported for para snowboard (IR of 40.5 per 1000 athlete days [95% CI 28.5 to 57.5]; p<0.02), particularly in the lower limb and head/face/neck anatomical areas. Across all sports at the Games, acute traumatic injuries (IR of 16.2 per 1000 athlete days [95% CI 13.2 to 19.8]) and injuries to the shoulder/arm/elbow complex (IR of 5.7 per 1000 athlete days [95% CI 4.2 to 7.8]) were most common. However, most injuries (78.9%) did not require time loss. Conclusion The new Paralympic Winter Games sport of Para snowboard requires attention to implement actions that will reduce injury risk. The shoulder was the most injured single joint—a consistent finding in elite para sport.
Prefrontal Structural Correlates of Cognitive Control during Adolescent Development: A 4-Year Longitudinal Study

Maturation of cognitive control abilities has been attributed to the protracted structural maturation of underlying neural correlates during adolescence. This study examined the relationship between development of two forms of cognitive control (proactive and reactive control) and structural maturation of the ACC, dorsolateral pFC, and ventrolateral pFC (vlPFC) between early and mid adolescence using a longitudinal design. Adolescents (n = 92) underwent baseline assessments when they were 12 years old and follow-up assessments approximately 4 years later. At each assessment, structural MRI scans were acquired, and a modified Stroop task was performed. Results showed longitudinal improvements in reactive control between early and mid adolescence. Furthermore, magnitude of the improvement in proactive control was associated with reduced thinning of the right vlPFC across the sample, whereas the magnitude of the improvements in reactive control was associated with reduced thinning of the left ACC in men alone. These findings suggest that individual differences in the maturation of ACC and vlPFC underlie the development of two distinct forms of cognitive control between early and mid adolescence as well as highlight sex differences in this relationship.
Pediatric Inflammatory CNV: A Case Series from a Tertiary Referral Centre

ABSTRACT Purpose: To report a case series of pediatric inflammatory choroidal neovascularization (CNV) seen at referral uveitis clinic. Methods: Records of pediatric patients with uveitis and inflammatory CNV between January 2000 and December 2012 were analyzed. Results: Ten eyes of seven patients were included. Mean age 12.6 years, mean follow-up 89.6 months. Three out of seven patients had bilateral CNV. Subfoveal CNV was noted in five eyes, extrafoveal CNV in three eyes and juxtafoveal and peripapillary CNV each in one eye. All patients received corticosteroids; immunosuppressives were used in three patients. Additional anti-VEGF injections were given, in six eyes, anti-VEGF and PDT in one eye and only PDT in three eyes. Conclusion: Pediatric inflammatory CNV though challenging, can be successfully managed with prompt therapy of the underlying uveitic disease, coupled with additional local therapy to selectively target the CNV.
When Less is More: Vaping Low-Nicotine vs. High-Nicotine E-Liquid is Compensated by Increased Wattage and Higher Liquid Consumption

(1) Background: Previous research (Van Gucht, Adriaens, and Baeyens, 2017) showed that almost all (99%) of the 203 surveyed customers of a Dutch online vape shop had a history of smoking before they had started using an e-cigarette. Almost all were daily vapers who used on average 20 mL e-liquid per week, with an average nicotine concentration of 10 mg/mL. In the current study, we wanted to investigate certain evolutions with regard to technical aspects of vaping behaviour, such as wattage, the volume of e-liquid used and nicotine concentration. In recent years, much more powerful devices have become widely available, e-liquids with very low nicotine concentrations have become the rule rather than the exception in the market supply, and the legislation has been adjusted, including a restriction on maximum nicotine concentrations to 20 mg/mL. (2) Methods: Customers (n = 150) from the same Dutch online vape shop were contacted (to allow a historical comparison), as well as 274 visitors from the Facebook group “Belgian Vape Bond” to compare between groups from two different geographies and/or vaping cultures. (3) Results: Most results were in line with earlier findings: Almost all surveyed vapers were (ex-)smokers, had started (80%) vaping to quit smoking and reported similar positive effects of having switched from smoking to vaping (e.g., improved health). A striking observation, however, was that whereas customers of the Dutch online vape shop used e-liquids with a similar nicotine concentration as that observed previously, the Belgian vapers used e-liquids with a significantly lower nicotine concentration but consumed much more of it. The resulting intake of the total quantity of nicotine did not differ between groups. (4) Conclusions: Among vapers, different vaping typologies may exist, depending on subcultural and/or geographic parameters. As a consequence of choosing low nicotine concentrations and consuming more e-liquid, the Belgian vapers may have a greater potential to expose themselves to larger quantities of harmful or potentially harmful constituents (HPHCs) released during vaping.
Synchronous hepatectomy and splenectomy vs hepatectomy for selected patients with hepatocellular carcinoma and clinically significant portal hypertension: A systematic review and meta‐analysis

This review aimed to evaluate the safety, feasibility, and effectiveness of synchronous hepatectomy and splenectomy for selected patients with hepatocellular carcinoma and clinically significant portal hypertension compared to hepatectomy alone. A systematic search in electronic databases was conducted. A total of 8 studies including 1445 patients were reviewed. While perioperative safety was satisfactory, synchronous hepatectomy and splenectomy were associated with a significant improvement of 5‐year overall survival (odds ratio = 1.81; 95% confidence interval: 1.35, 2.42; P < 0.0001).
Production of Dibromomethane and Changes in the Bacterial Community in Bromoform-Enriched Seawater

The responses of bacterial communities to halocarbon were examined using a 28-d incubation of bromoform- and methanol-enriched subarctic surface seawater. Significant increases were observed in dibromomethane concentrations and bacterial 16S rRNA gene copy numbers in the treated substrates incubated for 13 d. The accumulated bacterial community was investigated by denaturing gradient gel electrophoresis and amplicon analyses. The dominant genotypes corresponded to the genera Roseobacter, Lentibacter, and Amylibacter; the family Flavobacteriaceae; and the phylum Planctomycetes, including methylotrophs of the genus Methylophaga and the family Methylophilaceae. Therefore, various phylotypes responded along with the dehalogenation processes in subarctic seawater.
Health Promotion Interventions in Sports Clubs: Can We Talk About a Setting-Based Approach? A Systematic Mapping Review

Many researchers and authorities have recognized the important role that sports clubs can play in public health. In spite of attempts to create a theoretical framework in the early 2000s, a thorough understanding of sports clubs as a setting for health promotion (HP) is lacking. Despite calls for more effective, sustainable, and theoretically grounded interventions, previous literature reviews have identified no controlled studies assessing HP interventions in sports clubs. This systematic mapping review details how the settings-based approach is applied through HP interventions in sports clubs and highlights facilitators and barriers for sports clubs to become health-promoting settings. In addition, the mapped facilitators and barriers have been used to reformulate previous guidelines of HP in sports clubs. Seven databases were searched for empirical research published between 1986 and 2017. Fifty-eight studies were included, principally coming from Australia and Europe, describing 33 unique interventions, which targeted mostly male participants in team sports. The settings-based approach was not yet applied in sports clubs, as more than half of the interventions implemented in sports club targeted only one level of the socio-ecological model, as well as focused only on study participants rather than the club overall. Based on empirical data, the analysis of facilitators and barriers helped develop revised guidelines for sports clubs to implement settings-based HP. This will be particularly useful when implementing HP initiatives to aid in the development of sports clubs working with a whole setting approach.
A Collagen-Remodeling Gene Signature Regulated by TGF-β Signaling Is Associated with Metastasis and Poor Survival in Serous Ovarian Cancer

Purpose: To elucidate molecular pathways contributing to metastatic cancer progression and poor clinical outcome in serous ovarian cancer. Experimental Design: Poor survival signatures from three different serous ovarian cancer datasets were compared and a common set of genes was identified. The predictive value of this gene signature was validated in independent datasets. The expression of the signature genes was evaluated in primary, metastatic, and/or recurrent cancers using quantitative PCR and in situ hybridization. Alterations in gene expression by TGF-β1 and functional consequences of loss of COL11A1 were evaluated using pharmacologic and knockdown approaches, respectively. Results: We identified and validated a 10-gene signature (AEBP1, COL11A1, COL5A1, COL6A2, LOX, POSTN, SNAI2, THBS2, TIMP3, and VCAN) that is associated with poor overall survival (OS) in patients with high-grade serous ovarian cancer. The signature genes encode extracellular matrix proteins involved in collagen remodeling. Expression of the signature genes is regulated by TGF-β1 signaling and is enriched in metastases in comparison with primary ovarian tumors. We demonstrate that levels of COL11A1, one of the signature genes, continuously increase during ovarian cancer disease progression, with the highest expression in recurrent metastases. Knockdown of COL11A1 decreases in vitro cell migration, invasion, and tumor progression in mice. Conclusion: Our findings suggest that collagen-remodeling genes regulated by TGF-β1 signaling promote metastasis and contribute to poor OS in patients with serous ovarian cancer. Our 10-gene signature has both predictive value and biologic relevance and thus may be useful as a therapeutic target. Clin Cancer Res; 20(3); 711–23. ©2013 AACR.