Miracle-dz/UniFAR-FTUs huggingface dataset:
Resilience-based intervention for UK military recruits: a randomised controlled trial

Objectives We evaluated a military resilience intervention which aimed to help UK military recruits to manage their personal health and well-being more effectively. Methods Trainers within six pre-existing training teams were randomly allocated by team to deliver a resilience-based intervention (SPEAR) or usual training (control) during recruit training. 23 trainers delivered SPEAR; 18 delivered the control training. 707 recruits participated (n=358 SPEAR and n=349 controls). Outcome measures were obtained before and after recruit training and 3 months later. Measures of post-traumatic stress disorder (PTSD), common mental disorder (CMD) symptoms, alcohol use, homesickness and mental health stigmatisation were obtained at baseline. Repeat baseline scales plus measures of help-seeking, cohesion, leadership and training impact were obtained at the two follow-up points. Results Response rates were 91.7% (baseline), 98.1% (post) and 73.6% (follow-up). Following adjustment for potential confounders, levels of PTSD, CMD symptoms, alcohol misuse, help-seeking and homesickness were not significantly different between groups at any measurement point. Stigmatisation was significantly lower among SPEAR recipients at baseline but was not significantly different at the two follow-up points. Following adjustment for mental health confounders, there were no significant between-group differences in perceptions of leadership and cohesion and in ratings of six training outcomes at the two follow-up points. Conclusions We found no evidence that resilience-based training had any specific benefit to the health and well-being of UK military recruits.
Fronto‐insular‐parietal network engagement underlying arithmetic word problem solving

Mathematical word problems are ubiquitous and standard for teaching and evaluating generalization of mathematical knowledge for real‐world contexts. It is therefore concerning that the neural mechanisms of word problem solving are not well understood, as these insights represent strong potential for improving education and remediating deficits in this domain. Here, we investigate neural response to word problems via functional magnetic resonance imaging (fMRI). Healthy adults performed sentence judgment tasks on word problems that either contained one‐step mathematical operations, or nonarithmetic judgments on parallel narratives without any numerical information. Behavioral results suggested that the composite efficiency measurement of combining accuracy and RT did not differ between the two problem types. Arithmetic sentence judgments elicited greater activation in the fronto‐insular‐parietal network including intraparietal sulcus (IPS), dorsolateral prefrontal cortex (PFC), and anterior insula (AI) than narrative sentence judgment. Narrative sentence judgments, conversely, resulted in greater activation predominantly in the left ventral PFC, angular gyrus and perisylvian cortex compared with reading arithmetic sentences. Moreover, task‐dependent functional connectivity analyses showed the AI circuits were more strongly coupled with IPS during arithmetic sentence judgments than nonarithmetic sentences. Finally, activations in the IPS during arithmetic were highly correlated with out‐of‐scanner performance on a distinct set of problems with the same characteristics. These results show arithmetic word problem performance differences may rely more heavily on fronto‐insular‐parietal circuits for mathematical model building than narrative text comprehension of similar difficulty. More broadly, our study suggests that quantitative measurements of brain mechanisms can provide pivotal role for uncovering crucial arithmetic skills.
Gluten Immunogenic Peptides as Standard for the Evaluation of Potential Harmful Prolamin Content in Food and Human Specimen

Gluten is a complex mixture of storage proteins in cereals like wheat, barley, and rye. Prolamins are the main components of gluten. Their high content in proline and glutamine makes them water-insoluble and difficult to digest in the gastrointestinal tract. Partial digestion generates peptide sequences which trigger immune responses in celiac and gluten-sensitive patients. Gluten detection in food is challenging because of the diversity, in various food matrices, of protein proportions or modifications and the huge number of immunogenic sequences with differential potential immunoactivity. Attempts to develop standard reference materials have been unsuccessful. Recent studies have reported the detection of a limited number of dominant Gluten Immunogenic Peptides (GIP) that share similarities to epitopes presented in the α-gliadin 33-mer, which showed to be highly proteolytic resistant and is considered to be the most immunodominant peptide within gluten in celiac disease (CD). GIP were detectable and quantifiable in very different kind of difficult to analyze food, revealing the potential immunogenicity by detecting T-cell activity of celiac patients. But GIP were also found in stool and urine of celiac patients on a supposedly gluten-free diet (GFD), showing the capacity to resist and be absorbed and excreted from the body, providing the first simple and objective means to assess adherence to the GFD. Methods to specifically and sensitively detect the most active GIP in food and biological fluids are rational candidates may use similar analytical standard references for determination of the immunopathological risk of gluten exposure in gluten-related diseases.
Newborn screening for severe combined immunodeficiency and T‐cell lymphopenia

The development of a T cell receptor excision circle (TREC) assay utilizing dried blood spots (DBS) made possible universal newborn screening (NBS) for severe combined immunodeficiency (SCID) as a public health measure. Upon being flagged by an abnormal screening test in a SCID screening program, an infant can receive further diagnostic testing for SCID in the neonatal period, prior to onset of infectious complications, to permit immediate institution of protective measures and definitive, life‐saving treatment to establish a functional immune system. SCID screening is now the accepted standard of care in state public health departments across the United States, and it is being adopted in many countries. It has proven effective, with infants having this otherwise inapparent but serious, rare disorder achieving survival and immune reconstitution. In addition to bringing to attention infants with the primary screening target diseases, typical SCID and leaky SCID (due to hypomorphic mutations in known SCID genes), the NBS assay for insufficient TRECs in DBS also reveals infants with non‐SCID T lymphopenic conditions. Experience has accumulated regarding the range and limitations of diagnoses of newborns with low TRECs and low T cells. Previously unknown immune defects have been discovered, as well as conditions not formerly recognized to have low T cells in the neonatal period.
YAP1-Mediated CDK6 Activation Confers Radiation Resistance in Esophageal Cancer – Rationale for the Combination of YAP1 and CDK4/6 Inhibitors in Esophageal Cancer

Purpose: Esophageal cancer is a lethal disease that is often resistant to therapy. Alterations of YAP1 and CDK6 are frequent in esophageal cancer. Deregulation of both molecules may be responsible for therapy resistance. Experimental Design: Expressions of YAP1 and CDK6 were examined in esophageal cancer cells and tissues using immunoblotting and immunohistochemistry. YAP1 expression was induced in esophageal cancer cells to examine YAP1-mediated CDK6 activation and its association with radiation resistance. Pharmacologic and genetic inhibitions of YAP1 and CDK6 were performed to dissect the mechanisms and assess the antitumor effects in vitro and in vivo. Results: YAP1 expression was positively associated with CDK6 expression in resistant esophageal cancer tissues and cell lines. YAP1 overexpression upregulated CDK6 expression and transcription, and promoted radiation resistance, whereas treatment with the YAP1 inhibitor, CA3, strongly suppressed YAP1 and CDK6 overexpression, reduced Rb phosphorylation, as well as sensitized radiation-resistant/YAP1high esophageal cancer cells to irradiation. CDK4/6 inhibitor, LEE011, and knock down of CDK6 dramatically inhibited expression of YAP1 and sensitized resistant esophageal cancer cells to irradiation indicating a positive feed-forward regulation of YAP1 by CDK6. In addition, suppression of both the YAP1 and CDK6 pathways by the combination of CA3 and LEE011 significantly reduced esophageal cancer cell growth and cancer stem cell population (ALDH1+ and CD133+), sensitized cells to irradiation, and showed a strong antitumor effect in vivo against radiation-resistant esophageal cancer cells. Conclusions: Our results document that a positive crosstalk between the YAP1 and CDK6 pathways plays an important role in conferring radiation resistance to esophageal cancer cells. Targeting both YAP1 and CDK6 pathways could be a novel therapeutic strategy to overcome resistance in esophageal cancer.
New Molecular Mechanism Underlying Myc‐Mediated Cytochrome P450 2E1 Upregulation in Apoptosis and Energy Metabolism in the Myocardium

Background Canonical studies indicate that cytochrome P450 2E1 (CYP2E1) plays a critical role in the metabolism of xenobiotics and ultimately participates in tissue damage. CYP2E1 upregulates in the pathophysiological development of multiple diseases; however, the mechanism of CYP2E1 upregulation, particularly in heart disease, remains elusive. Methods and Results We found that the level of CYP2E1 increased in heart tissues from patients with hypertrophic cardiomyopathy; multiple mouse models of heart diseases, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and myocardial ischemia; and HL‐1 myocytes under stress. We determined that Myc bound to the CYP2E1 promoter and activated its transcription by bioinformatics analysis, luciferase activity, and chromatin immunoprecipitation, and Myc expression was modulated by extracellular signal–regulated kinases 1/2 and phosphatidylinositol 3 kinase/protein kinase B pathways under stress or injury in myocardium by signal transduction analysis. In addition, the level of oxidative stress and apoptosis gradually worsened with age in transgenic mice overexpressing CYP2E1, which was significantly inhibited with CYP2E1 knockdown. Conclusions Our results demonstrated that CYP2E1 is likely a sensor of diverse pathophysiological factors and states in the myocardium. Upregulated CYP2E1 has multiple pathophysiological roles in the heart, including increased oxidative stress and apoptosis as well as energy supply to meet the energy demand of the heart in certain disease states. Our discovery thus provides a basis for a therapeutic strategy for heart diseases targeting Myc and CYP2E1.
Hydroxytyrosol Exerts Anti-Inflammatory and Anti-Oxidant Activities in a Mouse Model of Systemic Inflammation

Hydroxytyrosol (3,4-dihydroxyphenil-ethanol, HT), the major phenol derived from olive oil consumption, has shown different anti-inflammatory and anti-oxidant activities in vitro which may explain the chronic-degenerative diseases preventive properties of olive oil. The aim of this study was to examine the ability of HT reduce inflammatory markers, Cyclooxygenase-2 (COX2) and Tumour Necrosis Factor alfa (TNF-α and oxidative stress in vivo on a mouse model of systemic inflammation. Balb/c mice were pre-treated with HT (40 and 80 mg/Kg b.w.) and then stimulated by intraperitoneal injection of lipopolysaccharide (LPS). Blood was collected to measure COX2 gene expression by qPCR and TNF-α level by ELISA kit in plasma. In addition, the total anti-oxidant power of plasma and the DNA damage were measured by FRAP test and COMET assay, respectively. LPS increased the COX2 expression, the TNF-α production and the DNA damage. HT administration prevented all LPS-induced effects and improved the anti-oxidant power of plasma. HT demonstrated in vivo anti-inflammatory and anti-oxidant abilities. The results may explain the health effects of olive oil in Mediterranean diet. HT represents an interesting molecule for the development of new nutraceuticals and functional food useful in chronic diseases prevention.
Association between aripiprazole pharmacokinetics and CYP2D6 phenotypes: A systematic review and meta‐analysis

The FDA has provided recommendations for aripiprazole use in CYP2D6 poor metabolizers (PMs); however, PMs make up <1% of the Asian population and no recommendation has been provided for intermediate metabolizers (IMs), who comprise a considerable proportion of the Asian population (64%‐70% occurrence of CYP2D6*10). This study aimed to investigate the characteristics of aripiprazole metabolism in IMs and other phenotypes by conducting the first meta‐analysis of the association among CYP2D6 phenotypes and aripiprazole pharmacokinetics (PK).
Improvement of the performance of survival prediction in the ageing blunt trauma population: A cohort study

Introduction The overestimation of survival predictions in the ageing trauma population results in negative benchmark numbers in hospitals that mainly treat elderly patients. The aim of this study was to develop and validate a modified Trauma and Injury Severity Score (TRISS) for accurate survival prediction in the ageing blunt trauma population. Methods This retrospective study was conducted with data from two Dutch Trauma regions. Missing values were imputed. New prediction models were created in the development set, including age (continuous or categorical) and Anesthesiologists Physical Status (ASA). The models were externally validated. Subsets were created based on age (≥75 years) and the presence of hip fracture. Model performance was assessed by proportion explained variance (Nagelkerke R2), discrimination (Area Under the curve of the Receiver Operating Characteristic, AUROC) and visually with calibration plots. A final model was created based on both datasets. Results No differences were found between the baseline characteristics of the development dataset (n = 15,530) and the validation set (n = 15,504). The inclusion of ASA in the prediction models showed significant improved discriminative abilities in the two subsets (e.g. AUROC of 0.52 [95% CI: 0.46, 0.58] vs. 0.74 [95% CI: 0.69, 0.78] for elderly patients with hip fracture) and an increase in the proportion explained variance (R2 = 0.32 to R2 = 0.35 in the total cohort). The final model showed high agreement between observed and predicted survival in the calibration plot, also in the subsets. Conclusions Including ASA and age (continuous) in survival prediction is a simple adjustment of the TRISS methodology to improve survival predictions in the ageing blunt trauma population. A new model is presented, through which even patients with isolated hip fractures could be included in the evaluation of trauma care.
Factors influencing doctors’ counselling on patients’ lifestyle habits: a cohort study

Background Lifestyle changes are important for prevention and treatment of many common diseases, and doctors have an important role in the lifestyle counselling of patients. It is important to know more about factors influencing lifestyle counselling. Aim To investigate the frequency of counselling about physical activity compared to that about alcohol habits; the impact of doctors’ own physical activity and alcohol habits on patient counselling about these lifestyle dimensions; and whether perceived mastery of clinical work or vulnerable personality have a confounding or moderating effect on these associations. Design & setting In this nationwide cohort survey, a total of 978 doctors in Norway were surveyed by postal questionnaires in 1993/94 and 2014. The response rate was 562/978 (57%). Method The outcome variables were questions on frequency of asking about alcohol and exercise habits. Explanatory variables were questions on doctors’ own exercise habits, drinking habits (using Alcohol Use Disorders Identification Test [AUDIT]), perceived mastery of clinical work, vulnerable personality, and specialty. Associations were studied by linear regression analysis. Results Of the 526 responders, 307 (58%) reported asking usually/often about exercise habits, while n = 140/524 (27%) usually/often asked about alcohol habits. A doctor's own physical activity level was associated with frequency of asking about physical activity (unstandardised regression coefficient [B] = 0.07; 95% confidence intervals [CI] = 0.01 to 0.13). There were no significant associations between doctors' own lifestyle habits and counselling on alcohol habits. Doctors with low levels of vulnerability asked more frequently about physical activity, regardless of their own physical activity habits (F = 2.41, P = 0.048). Conclusion Doctors’ own lifestyles influenced their preventive counselling about physical activity, but not about alcohol. Vulnerability moderated these effects, indicating the importance of early interventions to help doctors with a vulnerable personality to handle negative criticism from patients.
Quality-related events reported by community pharmacies in Nova Scotia over a 7-year period: a descriptive analysis.

BACKGROUND Quality-related events are defined as medication errors that reach the patient (e.g., incorrect drug, dose and quantity), in addition to medication errors that are intercepted before dispensing (i.e., near misses). The aim of this study is to quantify and characterize such events as reported by community pharmacies in a Canadian province. METHODS A retrospective analysis was conducted on quality-related events reported to the Community Pharmacy Incident Reporting system from 301 community pharmacies in Nova Scotia between Oct. 1, 2010, and June 30, 2017. We performed a descriptive analysis on these events with respect to the discoverer, patient outcome, medication system stages and type. RESULTS We identified 131 031 events reported by community pharmacies in Nova Scotia over the study period, 98 097 of which were quality-related events. Overall, 82.0% (n = 80 488) quality-related events did not reach the patient, and 0.95% (n = 928) were associated with patient harm. Incorrect dose or frequency, incorrect quantity and incorrect drug were the most common types of quality-related events reported. Most of the quality-related events occurred at order entry, followed by preparation and dispensing, and prescribing. INTERPRETATION Quality-related events reported by community pharmacies differ from those reported in institutional settings with respect to patient outcome, medication system stages and type. This analysis provides valuable information to guide quality improvement initiatives to strengthen medication safety in community pharmacies.
Mathematical Methods and Algorithms for Improving Near-Infrared Tunable Diode-Laser Absorption Spectroscopy

Tunable diode laser absorption spectroscopy technology (TDLAS) has been widely applied in gaseous component analysis based on gas molecular absorption spectroscopy. When dealing with molecular absorption signals, the desired signal is usually interfered by various noises from electronic components and optical paths. This paper introduces TDLAS-specific signal processing issues and summarizes effective algorithms so solve these.
A Wake-Up Call: We Need Phage Therapy Now

The rise of multidrug-resistant bacteria has resulted in an increased interest in phage therapy, which historically preceded antibiotic treatment against bacterial infections. To date, there have been no reports of serious adverse events caused by phages. They have been successfully used to cure human diseases in Eastern Europe for many decades. More recently, clinical trials and case reports for a variety of indications have shown promising results. However, major hurdles to the introduction of phage therapy in the Western world are the regulatory and legal frameworks. Present regulations may take a decade or longer to be fulfilled. It is of urgent need to speed up the availability of phage therapy.
Glaucoma in children with facial port wine stain

Purpose: To report on the clinical presentation and surgical treatment (procedure and outcome(s)) of glaucoma in children with facial port wine stain. Materials and methods: This is a retrospective chart review of children with facial port wine stain referred to Alexandria University paediatric ophthalmology practice from 2005 to 2016. The charts of 22 children (44 eyes) with facial port wine stain were reviewed. The data extracted included demographics, results of ophthalmic examination findings and treatment(s). The main outcome measures were the number of eyes stratified as glaucoma, glaucoma suspects and no glaucoma at the initial and final presentations. Results: The average age of presentation was 18.2 (±33.9) months. After a follow-up of over 16.1 (±24.8) months, there were 34%, 30% and 36% of the study eyes diagnosed as glaucoma, glaucoma suspects and no glaucoma, respectively with mean ± standard deviation of intraocular pressure of 20.6 ± 5.1, 13.6 ± 5.4 and 7.5 ± 1.7 mmHg. The majority (91%) of eyes presenting with glaucoma had clear corneas. In total, 11 eyes were operated upon for glaucoma. The recorded success rate was 91%. Two eyes developed a postoperative exudative choroidal detachment, of which one resolved spontaneously and the other was successfully managed by intravitreal gas injection. Conclusion: Glaucoma is a significant ocular hazard in children with facial port wine stain that may not be evident on the initial presentation. The presentation is usually with a clear cornea and surgical intervention is associated with a high success rate and a low rate of complications.
Effect of selective infiltration etching on the bond strength between zirconia and resin luting agents.

OBJECTIVE To evaluate the shear bond strength of resin cements to zirconia treated with the selective infiltration etching technique (SIE). MATERIALS AND METHODS Forty-seven zirconia specimens were prepared with a sequence of silicon carbide abrasives, cleaned in an ultrasonic bath. Three samples were separated for atomic force microscope (AFM) analyses (one nontreated for control, one sandblasted, and one selective infiltration etched) and the remaining were randomly distributed in four groups, according to the combination of surface treatment and resin cement: group 1a (sandblasting + Variolink II), group 1b (sandblasting + Panavia SA Plus), group 2a (SIE + Variolink II), group 2b (SIE + Panavia SA Plus). A composite resin cylinder (3 mm × 3 mm) was cemented to the zirconia surface, as per each group's specific protocol. After storing 24 hours in distilled water at 37°C, the specimens were tested for shear bond strength and the results were subjected to statistical analysis. RESULTS At 24 hours, the highest SBS values were observed in group 2b, where the SIE technique was used in conjunction with Panavia SA Plus. Lowest values were found in group 1a. Increased surface roughness was observed with SIE. CONCLUSIONS SIE significantly enhanced the resin bond strength to zirconia. However, cement selection was also an important factor, for both surface treatments tested. CLINICAL SIGNIFICANCE Use of SIE method combined with MDP monomer containing resin cement can provide clinically acceptable bond strength between zirconia and resin cement.