Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the effects of BCG vaccination in patients diagnosed with tuberculosis: observational study using the Enhanced Tuberculosis Surveillance system

Background Bacillus Calmette–Guérin (BCG) is one of the most widely-used vaccines worldwide. BCG primarily reduces the progression from infection to disease, however there is evidence that BCG may provide additional benefits. We aimed to investigate whether there is evidence in routinely-collected surveillance data that BCG vaccination impacts outcomes for tuberculosis (TB) cases in England. Methods We obtained all TB notifications for 2009–2015 in England from the Enhanced Tuberculosis surveillance system. We considered five outcomes: All-cause mortality, death due to TB (in those who died), recurrent TB, pulmonary disease, and sputum smear status. We used logistic regression, with complete case analysis, to investigate each outcome with BCG vaccination, years since vaccination and age at vaccination, adjusting for potential confounders. All analyses were repeated using multiply imputed data. Results We found evidence of an association between BCG vaccination and reduced all-cause mortality (aOR:0.76 (95%CI 0.64 to 0.89), P:0.001) and weak evidence of an association with reduced recurrent TB (aOR:0.90 (95%CI 0.81 to 1.00), P:0.056). Analyses using multiple imputation suggested that the benefits of vaccination for all-cause mortality were reduced after 10 years. Conclusions We found that BCG vaccination was associated with reduced all-cause mortality in people with TB although this benefit was less pronounced more than 10 years after vaccination. There was weak evidence of an association with reduced recurrent TB. Highlights Found evidence of an association between BCG vaccination and reduced all-cause mortality in TB cases. Weaker evidence of an association between BCG vaccination and reduced repeat TB episodes in TB cases. There was little evidence of an association with other TB outcomes. We explored the identified associations by age and time since vaccination.
Genome Sequences of an H9N2 Avian Influenza Virus Strain Found in Pakistan in 2017

In 2017, we isolated an H9N2 avian influenza virus in Pakistan. Genetic analysis showed that the A/chicken/Kasoor/SI36/2017(H9N2) isolate belongs to the G1 lineage. In addition, this isolate possesses mammalian host-specific mutations which could possibly favor interspecies transmission, suggesting that Pakistani H9N2 viruses are still potentially infectious for mammals. ABSTRACT In 2017, we isolated an H9N2 avian influenza virus in Pakistan. Genetic analysis showed that the A/chicken/Kasoor/SI36/2017(H9N2) isolate belongs to the G1 lineage. In addition, this isolate possesses mammalian host-specific mutations which could possibly favor interspecies transmission, suggesting that Pakistani H9N2 viruses are still potentially infectious for mammals.
Quantitative evaluation of the in vivo biocompatibility and performance of freeze-cast tissue scaffolds

Quantitative methods are little used for the in vivo assessment of tissue scaffolds to evaluate biocompatibility. To complement current histological techniques, we introduce as a measure of biocompatibility a straightforward, geometric analysis for the quantitative assessment of encapsulation thickness, cross-sectional area, and biomaterial shape. Advantages of this new technique are that it enables, on the one hand, a more complete and objective comparison of scaffolds with differing compositions, architectures, and mechanical properties, and, on the other, a more objective approach to their selection for a given application. In this contribution, we focus on freeze-cast polymeric scaffolds for tissue regeneration and their subcutaneous implantation in mice for biocompatibility testing. Initially, seven different scaffold types are screened. Of these, three are selected for systematic biocompatibility studies based on histopathological criteria: EDC-NHS-crosslinked bovine collagen, EDC-NHS-crosslinked bovine collagen-nanocellulose, and chitin. Geometric models developed to quantify scaffold size, ovalization, and encapsulation thickness are tested, evaluated, and found to be a powerful and objective metric for the in vivo assessment of biocompatibility and performance of tissue scaffolds.
External Validation of the ELAN‐HF Score, Predicting 6‐Month All‐Cause Mortality in Patients Hospitalized for Acute Decompensated Heart Failure

Background Our aim was to calibrate and externally revalidate the ELAN‐HF (European Collaboration on Acute Decompensated Heart Failure) score, to confirm and improve on a previous external validation of the risk score. Methods and Results The ELAN‐HF score predicts 6‐month all‐cause mortality in patients hospitalized for acute decompensated heart failure using absolute and percentage change of NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels in addition to clinical variables. For the external validation, we used the PRIMA II (Can NT‐proBNP–Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions? ) trial. For both data sets, observed versus predicted mortality was compared for the 4 risk categories; and the mean predicted mortality was plotted against the observed mortality with calculation of a correlation coefficient and SEE. The model discriminant ability was determined by comparing the C‐statistics for both data sets. The predicted versus actual 6‐month mortality values in the derivation cohort were 3.7% versus 3.6% for the low‐risk category, 9.4% versus 9.2% for the intermediate‐risk category, 24.2% versus 23.5% for the high‐risk category, and 54.2% versus 51.1% for the very‐high‐risk category. The correlation between predicted and observed mortality by deciles was 0.92, with an SEE of ±4%. In the validation cohort, predicted versus actual 6‐month mortality values were 3.0% versus 2.2% for the low‐risk category, 9.4% versus 8.2% for the intermediate‐risk category, 25.0% versus 22.9% for the high‐risk category, and 56.8% versus 53.6% for the very‐high‐risk category. The correlation between predicted and actual mortality by quintiles was 0.99, with an SEE of ±2%. There was no significant difference in C‐statistic between the derivation cohort (0.78; 95% CI, 0.74–0.82) and the validation cohort (0.77; 95% CI, 0.69–0.84; P=0.693). Conclusions Our study confirms that the ELAN‐HF score predicts accurately 6‐month mortality in patients hospitalized for acute decompensated heart failure with the use of easily obtained characteristics.
Use and validity of child neurodevelopment outcome measures in studies on prenatal exposure to psychotropic and analgesic medications – A systematic review

In recent years there has been increased attention to child neurodevelopment in studies on medication safety in pregnancy. Neurodevelopment is a multifactorial outcome that can be assessed by various assessors, using different measures. This has given rise to a debate on the validity of various measures of neurodevelopment. The aim of this review was twofold. Firstly we aimed to give an overview of studies on child neurodevelopment after prenatal exposure to central nervous system acting medications using psychotropics and analgesics as examples, giving special focus on the use and validity of outcome measures. Secondly, we aimed to give guidance on how to conduct and interpret medication safety studies with neurodevelopment outcomes. We conducted a systematic review in the MEDLINE, Embase, PsycINFO, Web of Science, Scopus, and Cochrane databases from inception to April 2019, including controlled studies on prenatal exposure to psychotropics or analgesics and child neurodevelopment, measured with standardised psychometric instruments or by diagnosis of neurodevelopmental disorder. The review management tool Covidence was used for data-extraction. Outcomes were grouped as motor skills, cognition, behaviour, emotionality, or “other”. We identified 110 eligible papers (psychotropics, 82 papers, analgesics, 29 papers). A variety of neurodevelopmental outcome measures were used, including 27 different psychometric instruments administered by health care professionals, 15 different instruments completed by parents, and 13 different diagnostic categories. In 23 papers, no comments were made on the validity of the outcome measure. In conclusion, establishing neurodevelopmental safety includes assessing a wide variety of outcomes important for the child’s daily functioning including motor skills, cognition, behaviour, and emotionality, with valid and reliable measures from infancy through to adolescence. Consensus is needed in the scientific community on how neurodevelopment should be assessed in medication safety in pregnancy studies. Review registration number: CRD42018086101 in the PROSPERO database.
The role of the optic tectum for visually evoked orienting and evasive movements

Significance The optic tectum (the superior colliculus in mammals) is central for visuomotor transformation in all vertebrates. Here, we investigate the mechanisms underlying the selection between approaching and evasive movements. We use an isolated eye–brain–spinal cord preparation from the lamprey that allows us to display different types of visual stimuli (e.g., looming stimuli) and, at the same time, record neural activity from specific brain regions and the behavioral output monitored through the ventral roots. We show that 2 classes of brainstem-projecting neurons in the deep layer of tectum, in interaction with local inhibitory interneurons, are responsible for the selective switch between visually triggered approaching or evasive movements. We suggest that these visual decision-making circuits are phylogenetically conserved throughout vertebrate evolution. As animals forage for food and water or evade predators, they must rapidly decide what visual features in the environment deserve attention. In vertebrates, this visuomotor computation is implemented within the neural circuits of the optic tectum (superior colliculus in mammals). However, the mechanisms by which tectum decides whether to approach or evade remain unclear, and also which neural mechanisms underlie this behavioral choice. To address this problem, we used an eye–brain–spinal cord preparation to evaluate how the lamprey responds to visual inputs with distinct stimulus-dependent motor patterns. Using ventral root activity as a behavioral readout, we classified 2 main types of fictive motor responses: (i) a unilateral burst response corresponding to orientation of the head toward slowly expanding or moving stimuli, particularly within the anterior visual field, and (ii) a unilateral or bilateral burst response triggering fictive avoidance in response to rapidly expanding looming stimuli or moving bars. A selective pharmacological blockade revealed that the brainstem-projecting neurons in the deep layer of the tectum in interaction with local inhibitory interneurons are responsible for selecting between these 2 visually triggered motor actions conveyed through downstream reticulospinal circuits. We suggest that these visual decision-making circuits had evolved in the common ancestor of vertebrates and have been conserved throughout vertebrate phylogeny.
Fruit and Vegetable Intake and Risk of Posttransplantation Diabetes in Renal Transplant Recipients

OBJECTIVE Posttransplantation diabetes mellitus (PTDM) contributes to risk for cardiovascular morbidity and mortality in renal transplant recipients (RTRs). In the general population, consumption of a diet containing few fruits and vegetables predisposes to type 2 diabetes. The role of diet as a potential modifiable risk factor for PTDM has not been explored. Our focus was to investigate the prospective associations of fruit and vegetable intake with risk of PTDM in stable RTRs. RESEARCH DESIGN AND METHODS We included 472 adult RTRs who had a functioning graft ≥1 year. Fruit and vegetable intake was assessed by using a 177-item food frequency questionnaire. PTDM was defined according the American Diabetes Association’s diagnostic criteria for diabetes. RESULTS During 5.2 years of follow-up, 52 RTRs (11%) developed PTDM. Fruit intake was not associated with PTDM (hazard ratio [HR] 0.90 [95% CI 0.79–1.03] per 2log g/day; P = 0.13), whereas vegetable intake was inversely associated with PTDM (HR 0.77 [95% CI 0.63–0.94] per 2log g/day; P = 0.009). Mediation analyses revealed that ±50% of the association between vegetable intake and PTDM was mediated by variations in key components of the metabolic syndrome (i.e., HDL cholesterol, triglycerides, and waist circumference) as determined by the National Cholesterol Education Program’s Adult Treatment Panel III Expert Panel. CONCLUSIONS In this study vegetable intake, but not fruit intake, was associated with lower risk of PTDM in RTRs, likely largely through beneficial effects on key components of the metabolic syndrome. These findings further support accumulating evidence that supports a recommendation of higher vegetable intake by RTRs.
A Rasch analysis of the lumbar spine instability questionnaire

ABSTRACT Purpose: A 2014 study found that the Lumbar Spine Instability questionnaire predicts response to two different types of exercise therapy. This is the first decision tool that has predicted response to exercise for chronic low back pain. The objective of this study was to evaluate the Lumbar Spine Instability questionnaire using Rasch analysis. Methods: Baseline data from patients included in a randomized controlled trial with chronic non-specific low back pain were included. Rasch Measurement Theory was used to assess the ordering of items along a common scale, data-to-model fit, Person Separation Index, unidimensionality and Differential Item Functioning. Results: Responses from 172 patients (102 females) underwent Rasch analysis. All Lumbar Spine Instability questionnaire items had fit residuals between ± 2.5 and Chi-Square values were non-significant with Bonferroni corrections. The Lumbar Spine Instability questionnaire demonstrated a Person Separation Index of 0.64, which is below the recommended cut-off of 0.7. Differential Item Functioning by different pain levels was identified for one item. Conclusion: The Lumbar Spine Instability questionnaire was found to be unidimensional, suggesting that the use of a summary score is appropriate. However, the low Person Separation Index value suggests that more items may be needed to increase the questionnaire’s ability to discriminate among individuals with high and low clinical instability.
Baseline Absolute Lymphocyte Count and ECOG Performance Score Are Associated with Survival in Advanced Non-Small Cell Lung Cancer Undergoing PD-1/PD-L1 Blockade

Immune-checkpoint blockade in front-line or second-line treatment improves survival in advanced non-small cell lung cancer (aNSCLC) when compared with chemotherapy alone. However, easily applicable predictive parameters are necessary to guide immune-checkpoint inhibition in clinical practice. In this retrospective bi-centric analysis, we investigated the impact of baseline patient and tumor characteristics on clinical outcome in aNSCLC patients treated with programmed cell death protein 1(PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors. Between May 2015 and January 2018, 142 unselected consecutive NSCLC patients received PD-1/PD-L1 inhibitors during the course of disease. In multivariate analysis, we identified the Eastern Cooperative Oncology Group (ECOG) performance status (ECOG > 1 versus ECOG ≤ 1, HR: 3.23, 95%CI: 1.58–6.60, P = 0.001), baseline absolute lymphocyte count (ALC; high: >0.93 × 109/L versus low: ≤ 0.93 × 109/L, HR: 0.38, 95%CI: 0.23–0.62, P < 0.001), prior or concomitant anti-vascular endothelial growth factor (VEGF) targeting therapy (yes versus no, HR: 2.18, 95%CI: 1.15–4.14, P = 0.017) and TNM stage (IV versus III, HR: 4.18, 95%CI: 1.01–17.36, P = 0.049) as the most relevant parameters for survival. Neither antibiotic exposure (antibiotic-positive versus antibiotic-negative, HR: 0.90, 95%CI: 0.56–1.45, P = 0.675), nor PD-L1 expression on tumor cells (≥1% versus <1%, HR: 0.68, 95%CI: 0.41–1.13, P = 0.140) was associated with survival. Baseline ECOG performance status and ALC were associated with survival in aNSCLC patients treated with PD-1/PD-L1 inhibitors and assessment of these parameters could be suitable in clinical practice.
Nutraceutical and pharmaceutical cocktails did not improve muscle function or reduce histological damage in d2-mdx mice.

Progressive muscle injury and weakness are hallmarks of Duchenne muscular dystrophy. We showed previously that quercetin (Q) partially protected dystrophic limb muscles from disease-related injury. As quercetin activates PGC-1α through Sirtuin-1, an NAD+-dependent deacetylase, the depleted NAD+ in dystrophic skeletal muscle may limit quercetin efficacy, hence, supplementation with the NAD+ donor, nicotinamide riboside (NR), may facilitate quercetin efficacy. Lisinopril (Lis) protects skeletal muscle and improves cardiac function in dystrophin-deficient mice, therefore it was included in this study to evaluate the effects of lisinopril used with quercetin and NR. Our purpose was to determine the extent to which Q, NR, and Lis decreased dystrophic injury. We hypothesized that Q, NR or Lis alone would improve muscle function and decrease histological injury and when used in combination would have additive effects. Muscle function of 11-month-old DBA (healthy), D2-mdx (dystrophin-deficient), and D2-mdx mice was assessed following treatment with Q, NR, and/or Lis for 7-months. To mimic typical pharmacology of DMD patients a group was treated with prednisolone (Pred) in combination with Q, NR and Lis. At 11-months of age, dystrophin deficiency decreased specific tension and tetanic force in the soleus and extensor digitorum longus muscles and was not corrected by any treatment. Dystrophic muscle was more sensitive to contraction-induced injury, which was partially offset in the QNRLisPred group, while fatigue was similar between all groups. Treatments did not decrease histological damage. These data suggest treatment with Q, NR, Lis and Pred failed to adequately maintain dystrophic limb muscle function or decrease histological damage.
Evaluation of Interfacial Fracture Toughness and Interfacial Shear Strength of Typha Spp. Fiber/Polymer Composite by Double Shear Test Method

The aim of this paper is to evaluate the Mode II interfacial fracture toughness and interfacial shear strength of Typha spp. fiber/PLLA and Typha spp. fiber/epoxy composite by using a double shear stress method with 3 fibers model composite. The surface condition of the fiber and crack propagation at the interface between the fiber and the matrix are observed by scanning electron microscope (SEM). Alkali treatment on Typha spp. fiber can make the fiber surface coarser, thus increasing the value of interfacial fracture toughness and interfacial shear strength. Typha spp. fiber/epoxy has a higher interfacial fracture value than that of Typha spp. fiber/PLLA. Interfacial fracture toughness on Typha spp. fiber/PLLA and Typha spp. fiber/epoxy composite model specimens were influenced by the matrix length, fiber spacing, fiber diameter and bonding area. Furthermore, the interfacial fracture toughness and the interfacial fracture shear stress of the composite model increased with the increasing duration of the surface treatment.
Membrane curvature sensing of the lipid-anchored K-Ras small GTPase

Proteolipid nanoassemblies of K-Ras and lipids in the plasma membrane sense changing membrane curvature architecture and convert mechanical perturbations to mitogenic signaling. Plasma membrane (PM) curvature defines cell shape and intracellular organelle morphologies and is a fundamental cell property. Growth/proliferation is more stimulated in flatter cells than the same cells in elongated shapes. PM-anchored K-Ras small GTPase regulates cell growth/proliferation and plays key roles in cancer. The lipid-anchored K-Ras form nanoclusters selectively enriched with specific phospholipids, such as phosphatidylserine (PS), for efficient effector recruitment and activation. K-Ras function may, thus, be sensitive to changing lipid distribution at membranes with different curvatures. Here, we used complementary methods to manipulate membrane curvature of intact/live cells, native PM blebs, and synthetic liposomes. We show that the spatiotemporal organization and signaling of an oncogenic mutant K-RasG12V favor flatter membranes with low curvature. Our findings are consistent with the more stimulated growth/proliferation in flatter cells. Depletion of endogenous PS abolishes K-RasG12V PM curvature sensing. In cells and synthetic bilayers, only mixed-chain PS species, but not other PS species tested, mediate K-RasG12V membrane curvature sensing. Thus, K-Ras nanoclusters act as relay stations to convert mechanical perturbations to mitogenic signaling.
Prucalopride in Gastroparesis: A Randomized Placebo-Controlled Crossover Study.

OBJECTIVES Prokinetics are considered the preferred treatment option for gastroparesis, but evidence of their efficacy is scarce. Prucalopride, a selective 5-hydroxytryptamine 4 receptor agonist used in the treatment of constipation, is able to enhance the gastric emptying rate. In a double-blind, randomized, placebo-controlled crossover study, we evaluated the efficacy of prucalopride to improve the gastric emptying rate and symptoms in patients with gastroparesis. METHODS Thirty-four patients with gastroparesis (28 idiopathic, 7 men, mean age 42 ± 13 years) were evaluated in a double-blind crossover trial of 4-week treatment periods with placebo or prucalopride 2 mg q.d. , separated by 2 weeks of washout. The primary end point was the change in symptom severity, assessed by the Gastroparesis Cardinal Symptom Index; secondary end points comprised the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index, the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life, and daily diaries, and the gastric emptying rate was assessed by the C-octanoic acid breath test. RESULTS Three patients were lost to follow-up. One serious adverse event occurred (small bowel volvulus in the prucalopride group), and 3 patients dropped out because of adverse events of nausea and headache (all prucalopride). For the entire patient group, compared with placebo, prucalopride significantly improved the total Gastroparesis Cardinal Symptom Index (1.65 ± 0.19 vs 2.28 ± 0.20, P < 0.0001) and the subscales of fullness/satiety, nausea/vomiting, and bloating/distention. Prucalopride significantly improved the overall Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life score (1.15 ± 0.16 vs 1.44 ± 0.16, P < 0.05) and the domains of clothing and diet. The gastric half emptying time was significantly enhanced by prucalopride compared with placebo and baseline (98 ± 10 vs 143 ± 11 and 126 ± 13 minutes, P = 0.005 and <0.001, respectively). These significant improvements were also found when considering only the idiopathic gastroparesis subgroup. DISCUSSION In a cohort of patients with predominantly idiopathic gastroparesis, 4 weeks of prucalopride treatment significantly improved symptoms and quality of life and enhanced gastric emptying compared with placebo.