Miracle-dz/UniFAR-FTUs huggingface dataset:
Severity of coeliac disease and clinical management study when using a CYP3A4 metabolised medication: a phase I pharmacokinetic study

Objective Severity of coeliac disease depends in part on the extent of small intestinal mucosa injury. Patients with the most abnormal pathology have loss of duodenal villi CYP3A4, a drug-metabolising enzyme that inactivates many drugs. These patients are hypothesised to have greater systemic concentrations of felodipine, a drug which normally has low oral bioavailability secondary to intestinal CYP3A4-mediated metabolism. It serves as a representative for a class containing many medications. Design A phase I, open-label, single-dose, pharmacokinetic study. Setting London, Ontario, Canada. Participants Patients with coeliac disease (n=47) with positive serology and healthy individuals (n=68). Main outcome measures Patients with coeliac disease—upper gastrointestinal endoscopy and oral felodipine pharmacokinetics study within a 3-week period. Healthy individuals—oral felodipine pharmacokinetics study with water and grapefruit juice. Results Coeliac stratification categories: Group A (n=15, normal), B+C (n=16, intraepithelial lymphocytosis with/without mild villous blunting) and D (n=16, moderate/severe villous blunting). Groups A, B+C and D had linear trends of increasing felodipine AUC0–8; mean±SEM, 14.4±2.1, 17.6±2.8, 25.7±5.0; p<0.05) and Cmax (3.5±0.5, 4.0±0.6, 6.4±1.1; p<0.02), respectively. Healthy subjects receiving water had lower felodipine AUC0–8 (11.9±0.9 vs 26.9±0.9, p=0.0001) and Cmax (2.9±0.2 vs 7.7±0.2, p=0.0001) relative to those receiving grapefruit juice. Conclusions Increased felodipine concentrations in patients with coeliac disease were most probably secondary to decreased small intestinal CYP3A4 expression. Patients with severe coeliac disease and healthy individuals with grapefruit juice had equivalently enhanced effect. Thus, patients with severe coeliac disease would probably experience similarly altered drug response, including overdose toxicity, from many important medications known to be metabolised by CYP3A4. Patients with coeliac disease with severe disease should be considered for other clinical drug management, particularly when there is the potential for serious drug toxicity.
Impact of preterm birth on brain development and long-term outcome: protocol for a cohort study in Scotland

Introduction Preterm birth is closely associated with altered brain development and is a leading cause of neurodevelopmental, cognitive and behavioural impairments across the life course. We aimed to investigate neuroanatomic variation and adverse outcomes associated with preterm birth by studying a cohort of preterm infants and controls born at term using brain MRI linked to biosamples and clinical, environmental and neuropsychological data. Methods and analysis Theirworld Edinburgh Birth Cohort is a prospective longitudinal cohort study at the University of Edinburgh. We plan to recruit 300 infants born at <33 weeks of gestational age (GA) and 100 healthy control infants born after 37 weeks of GA. Multiple domains are assessed: maternal and infant clinical and demographic information; placental histology; immunoregulatory and trophic proteins in umbilical cord and neonatal blood; brain macrostructure and microstructure from structural and diffusion MRI (dMRI); DNA methylation; hypothalamic–pituitary–adrenal axis activity; social cognition, attention and processing speed from eye tracking during infancy and childhood; neurodevelopment; gut and respiratory microbiota; susceptibility to viral infections; and participant experience. Main analyses include creation of novel methods for extracting information from neonatal structural and dMRI, regression analyses of predictors of brain maldevelopment and neurocognitive outcome associated with preterm birth, and determination of the quantitative predictive performance of MRI and other early life factors for childhood outcome. Ethics and dissemination Ethical approval has been obtained from the National Research Ethics Service (NRES), South East Scotland Research Ethics Committee (NRES numbers 11/55/0061 and 13/SS/0143 (phase I) and 16/SS/0154 (phase II)), and NHS Lothian Research and Development (2016/0255). Results are disseminated through open access journals, scientific meetings, social media, newsletters anda study website (www.tebc.ed.ac.uk), and we engage with the University of Edinburgh public relations and media office to ensure maximum publicity and benefit.
Engineered Recombinant Single Chain Variable Fragment of Monoclonal Antibody Provides Protection to Chickens Infected with H9N2 Avian Influenza

Passive immunisation with neutralising antibodies can be a potent therapeutic strategy if used pre- or post-exposure to a variety of pathogens. Herein, we investigated whether recombinant monoclonal antibodies (mAbs) could be used to protect chickens against avian influenza. Avian influenza viruses impose a significant economic burden on the poultry industry and pose a zoonotic infection risk for public health worldwide. Traditional control measures including vaccination do not provide rapid protection from disease, highlighting the need for alternative disease mitigation measures. In this study, previously generated neutralizing anti-H9N2 virus monoclonal antibodies were converted to single-chain variable fragment antibodies (scFvs). These recombinant scFv antibodies were produced in insect cell cultures and the preparations retained neutralization capacity against an H9N2 virus in vitro. To evaluate recombinant scFv antibody efficacy in vivo, chickens were passively immunized with scFvs one day before, and for seven days after virus challenge. Groups receiving scFv treatment showed partial virus load reductions measured by plaque assays and decreased disease manifestation. These results indicate that antibody therapy could reduce clinical disease and shedding of avian influenza virus in infected chicken flocks.
Onco-Surgical Management of Liver Metastases from Colorectal Cancer

Metastatic disease is the main cause of death in patients with colorectal cancer and the most frequent location of metastases is in the liver. The treatment of liver metastases of colorectal origin is multimodal and should be based on a multidisciplinary team decision. A systematic review of the literature revealed that the number of liver metastases, their maximum size, CEA level, advanced age of the patients, and presence of extrahepatic disease are no longer contraindications to liver resection. The resecta‐ bility rate of colorectal liver metastases increased from 10 to almost 40%, enabling 5‐ year overall survival rates higher than 30%. Short‐term and long‐term results achieved by simultaneous resection (SR) are similar to those achieved by staged resections in patients with synchronous colorectal liver metastases. Whenever possible, major hepatectomies should be replaced by ultrasound‐guided limited liver resections, and primary tumor should be approached in a minimally invasive manner. Even initially unresectable colorectal liver metastases could be rendered resectable by an aggressive multimodal approach (“two‐stage” hepatectomies, hepatectomy after portal vein embolization/ligation, resection after conversion chemotherapy, and hepatectomy associated with ablation). The presence of extrahepatic metastases is no longer a contraindication to liver resection, when extrahepatic disease is resectable. Repeat hepatectomy improves survival in patients with recurrent liver metastases.
INSECTICIDAL ACTIVITIES OF CINNAMOMUM TAMALA (LAURACEAE) ESSENTIAL OIL AGAINST SITOPHILUS ORYZAE L. (COLEOPTERA: CURCULIONIDAE)

Cinnamomum tamala (Lauraceae) essential oil and its major constituent, eugenol were evaluated for repellent, insecticidal, feeding inhibitory, oviposition inhibitory and acetylcholinesterase enzyme inhibitory activities in rice weevil, Sitophilus oryzae . In repellency assay, C. tamala oil and eugenol repelled S. oryzae adults significantly at 0.2% concentration. Essential oil of C. tamala and eugenol caused fumigant and contact toxicity in S. oryzae adults. In fumigation toxicity assay, median lethal concentrations (LC 50 ) were found 0.249 and 0.198 μl/cm 3 ; and 0.167 and 0.152 μl/cm 3 of C. tamala oil and eugenol after 24 and 48 h exposure of S. oryzae adults respectively. In contact toxicity assay, median lethal concentrations (LC 50 ) were found 0.241 and 0.218 μl/cm 2 ; and 0.185 and 0.126 μl/cm 2 of C. tamala oil and eugenol after 24 and 48 h exposure of S. oryzae adults respectively. Essential oil of C. tamala and eugenol showed feeding deterrent activity and oviposition inhibition activity in S. oryzae adults when exposed to sub-lethal concentrations. Fumigation of S. oryzae with C. tamala oil and eugenol inhibited acetylcholinesterase enzyme (AchE) activity. This study concludes that C. tamala and its components can be used as alternative in management of stored-grain insects .
Efficacy of a knowledge translation approach in changing allied health practitioner use of evidence-based practices with children with cerebral palsy: a before and after longitudinal study

Abstract Purpose To investigate the effect of a knowledge translation intervention on knowledge and frequency of routine evidence-based assessment behaviours of healthcare professionals working with children with cerebral palsy. Methods A before-and-after longitudinal study was conducted in five disability organisations. Four organisations (Commencing Knowledge Translation group) implemented a multifaceted intervention: knowledge brokers, targeted education, electronic-evidence library, and clinical outcomes database. These strategies were already in place at the fifth organisation (Comparison group). Outcomes evaluated at 0, 6, 12, and 24 months were health-professional knowledge and routine assessment behaviours (self-report and “completeness” of clinical assessment). Generalised estimating equations determined longitudinal changes. Results Four hundred and forty-seven professionals involved 861 children in the study. The Comparison group had higher knowledge and routine assessment behaviours at baseline. Professional knowledge in both groups remained stable (differences in change from baseline to 24 months: 0.3 units, 95%CI: −0.76 to 1.36). Assessment completeness of the Comparison group was stable (baseline mean 68 units, 95%CI: 65–71); the Commencing Knowledge Translation group improved from baseline mean 35 units (95%CI: 33–36), peaking at 12 months (mean 68 (95%CI: 65–71). Conclusions Multifaceted organisational support improved health-professional routine evidence-based assessment behaviours with children with cerebral palsy, despite no change in knowledge. Trial registration This trial was not a controlled health care intervention and was registered retrospectively: ACTRN12616001616460. The protocol of the trial was published in 2015 as follows: Imms et al. [6]. Implications for rehabilitation A multifaceted knowledge translation intervention increased allied health professionals’ assessment behaviours. Knowledge translation strategies can be chosen to target change in knowledge and/or change in behaviour. Knowledge translation interventions should be designed to address organisational barriers and enhance organisational supports. Interventions that target healthcare professionals’ behaviour directly can be effective even if their knowledge does not change.
MR Thermometry in Cerebrovascular Disease: Physiologic Basis, Hemodynamic Dependence, and a New Frontier in Stroke Imaging

SUMMARY: The remarkable temperature sensitivity of the brain is widely recognized and has been studied for its role in the potentiation of ischemic and other neurologic injuries. Pyrexia frequently complicates large-vessel acute ischemic stroke and develops commonly in critically ill neurologic patients; the profound sensitivity of the brain even to minor intraischemic temperature changes, together with the discovery of brain-to-systemic as well as intracerebral temperature gradients, has thus compelled the exploration of cerebral thermoregulation and uncovered its immutable dependence on cerebral blood flow. A lack of pragmatic and noninvasive tools for spatially and temporally resolved brain thermometry has historically restricted empiric study of cerebral temperature homeostasis; however, MR thermometry (MRT) leveraging temperature-sensitive nuclear magnetic resonance phenomena is well-suited to bridging this long-standing gap. This review aims to introduce the reader to the following: 1) fundamental aspects of cerebral thermoregulation, 2) the physical basis of noninvasive MRT, and 3) the physiologic interdependence of cerebral temperature, perfusion, metabolism, and viability.
Block Matching and 3D Filtering for Image Denoising

We present a novel approach to still image denoising based on effective filtering in 3D transform domain by combining sliding-window transform processing with block-matching. We process blocks within the image in a sliding manner and utilize the block-matching concept by searching for blocks which are similar to the currently processed one. The matched blocks are stacked together to form a 3D array and due to the similarity between them, the data in the array exhibit high level of correlation. We exploit this correlation by applying a 3D decorrelating unitary transform and effectively attenuate the no1ise by shrinkage of the transform coefficients. The subsequent inverse 3D transform yields estimates of all matched blocks. After repeating this procedure for all image blocks in sliding manner, the final estimate is computed as weighed average of all overlapping block estimates. A fast and efficient algorithm implementing the proposed approach is developed. The experimental results show that the proposed method delivers state-of-art denoising performance, both in terms of objective criteria and visual quality.
THE LOW VOLATILITY PUZZLE: EVIDENCE FROM KSE 100 OF PAKISTAN

Modern portfolio theory suggests that investors hold a portfolio of stocks to diversify idiosyncratic risk. The capital asset pricing model (CAPM) builds on the portfolio theory and predicts that all investors hold the market portfolio in equilibrium. As a result, only systematic risk is priced in equilibrium and idiosyncratic risk is not.This study investigates the relation between idiosyncratic volatility and returns in Karachi Stock Exchange (KSE) 100 index of Pakistan for the period July 2009 to June 2015. The results show that there is a negative relationship between idiosyncratic risk and expected returns and the internationally documented strong performance of low volatility stocks relative to high volatility stocks is present in Pakistan. Terms: Risk Management, Pakistan Stock Exchange, Stock Market, Volatility, Portfolio Management, CAPM, Risk
Middle Eastern Plant Extracts: An Alternative to Modern Medicine Problems

Middle Eastern countries are primarily known for their dry sand deserts; however, they have a wider physiographic range which includes upland plateau and mountain ranges. The Middle East is home to various types of plants, such as Phoenix dactylifera (date palm tree), Scrophularia striata (herbaceous plants), and Opuntia ficus-indica (cactus). These plants have been found to have various types of bioactivities, such as antimicrobial activities against both bacteria and fungi, in addition to exhibiting anti-inflammatory effects and anti-cancer characteristics which can be utilized in the clinical setting for treatment. Due to limited reviews focusing on plant extracts from the Middle East, we aim to provide a discourse on plants from this region which have various bioactivities and to provide information on the compounds that can be identified from these plants. This is to enhance our understanding to improve modern medicine problems such as antimicrobial resistance and to find an alternative cure for cancer. It is hoped that the collation of information from this review will enable an assessment of the direct role of Middle Eastern plants in providing therapeutic options to address the predicaments in the medical field.
ADVANCEMENT IN ENDOPHYTIC MICROBES FROM MEDICINAL PLANTS

This overview firstly highlights biology of endophytic microbes from medicinal plants as well as their chemistry with emphasis on the important merging of microbiology and natural products chemistry and its role in improving our current knowledge of endophytic associations in medicinal plants. Secondary metabolites of medicinal plants-derived endophytes reported in recent years are grouped according to their bioactive properties including antitumor, antimicrobial, growth-promoting, antioxidant, antithrombotic, insecticide and other functions. New insights on distributing characteristics and biodiversity of these endophytes including bacteria, actinomycetes and fungi are also presented. It suggested that endophytic microbe from medicinal plant is a treasure trove of bioactive natural products with a good and potential application prospect in pharmacy and agriculture. INTRODUCTION: The term ‘endophyte’ is a kind of microbes which reside in the intracellular or intercellular area of healthy plant tissues during their periods of life or the whole, and don't cause any obvious symptoms or distinct negative effects in their plant hosts 1 . Endophytes are the normal organism in plant tissues and shown to be an important part of microecosystem 2 . Investigation of endophytes had not become a hot spot globally until a taxol and taxane producing endophyte, Taxomyces andreanae, isolated from Taxus brevifolia was reported in 1993 3 . Nowadays, more attention is being worldwide paid to endophytic microbes by microbiologists and natural product chemists because of their abundant biological and chemical diversity. Endophytes originated from the formation of higher plants or vascular plants on the earth 4, 5 . During the long period of co-evolution with host plants, endophytes had adapted themselves to the niches and formed a completely compatible symbiont via gene regulation 2 . In this micro-ecoenvironment, host plants provide endophytes with photosynthetic products and minerals for their normal growth while `endophytes promote the growth and chemical defense of host plants by directly providing with valuable metabolites or transferring the corresponding genes to the host genome 6, 7 . So, endophytic microbes can improve the resistance of their hosts to adverse biotic factors (such as plant pathogens, herbivore, insects, etc.)
Spectrum Sensing Detection Techniques for Overlay Users

Spectrum allocated Agency (FCC) is currently working on the concept of white space users “borrowing” spectrum from free license holders temporarily to improve the spectrum utilization, i.e known as dynamic spectrum access (DSA). CRN systems can utilize dispersed spectrum, and thus such approach is known as dispersed spectrum cognitive radio systems. This project provides a tradeoff between a false alarm probability (Pf) and the signal to noise ratio (SNR) value of any spectrum detector to have a certain performance. Moreover, the performance of the cyclostationary detector (CD) and the matched filter detector (MF) is better than the energy detector(ED) especially at low signal to noise ratio values. Unfortunately, the cyclostationary spectrum sensing method, performance is not satisfying when the wireless fading channels are employed. In this project we provide the best trade off for spectrum usage for over lay users.
Targeting macrophages: a novel avenue for cancer drug discovery

ABSTRACT Introduction: Tumor-associated macrophages (TAMs) make up a significant portion of the tumor microenvironment. Emerging clinical evidence indicate that cytokines present in the tumor microenvironment influence TAMs to play an immunosuppressive role by acquiring a pro-tumoral phenotype. However, TAMs are inherently plastic cells that can be phenotypically reprogrammed to elicit an anti-tumoral response. Therapeutic strategies that focus on targeting TAMs have opened new avenues for drug discoveries. Areas covered: This review discusses recent developments in TAM targeted immunotherapy in both preclinical and clinical settings. This article highlights the potential signaling pathways that can be targeted for macrophage reprogramming and discusses the progress of current clinical trials involved in TAMs targeting. Novel nanoparticle-based drug delivery strategies involved in macrophage-based cancer therapeutics and diagnostics are also discussed. Expert opinion: TAM targeted therapies have limited success in clinics due to reasons such as insufficient inhibition of signaling pathways, lower drug accumulation in the tumor, activation of feedback signaling pathways that induce resistance to monotherapies and systemic dose-related toxicities. Nanoparticle-based delivery platforms could overcome these challenges since they enable encapsulation of multiple drugs that target different signaling pathways and enhance intratumoral delivery and can enable delivery of imaging agents.
Overview of Source Code Plagiarism in Programming Courses

: Plagiarism of programming source codes is an undesirable situation in the many fields of software development world. Especially in educational field, it is obviously realized that plagiarism in programming courses increases consistently. The aim of this study is attempting to answer questions such as “which codes are similar? ”, “what similarity ratios are? ” in order to prevent plagiarism among university students who attend programming courses. While developing the proposed methodology, N-gram similarity calculation method and Vector Space Model (VSM) were considered. Information Retrieval (IR) System and Cosine Normalization (CN) methods were utilized to calculate similarity ratios. Experimental study was performed on the dataset yielded by changing source code examples in different forms. The results obtained provide convincing evidence that the study is fit the purpose.
Biochemical Indices in Ecology: A Catalyst in Environmental Study

Kiyoshi Kikuchi1,2,3,4*, Motohiro Morioka2, Yoshinaka Murai1, Eiichiro Tanaka1 1Division of Brain Science, Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan 2Department of Neurosurgery, Kurume University School of Medicine, 67 Asahimachi, Kurume 830-0011, Japan 3Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan 4Department of Pharmacology, Faculty of Dentistry, Mahidol University, 6 Yothe Road, Rajthevee, Bangkok 10400, Thailand
Hybridization kinetics of DNA fragments in the presence of ligands intercalating into DNA-duplexes

Abstract In this work the hybridization kinetics of DNA fragments on underlayer has been studied, when besides single-stranded DNA molecules there are also ligands in the medium that are able to intercalate into DNA-duplexes. A system of differential equations was obtained that describes the correlative change of the number of DNA-duplexes on the underlayer and the change of the number of ligands intercalating into DNA-duplexes. It was shown that the rate of underlayer filling by DNA-duplexes increases along with the enhancement of both equilibrium constant of formation reaction of DNA-duplexes and the concentration of DNA targets in the solution. It was also shown that the intercalation kinetics of ligands into DNA-duplexes relevantly depends on relation of dissociation rate constant of DNA-duplex to dissociation rate of the ligand complex with DNA-duplex. Communicated by Ramaswamy H. Sarma