Miracle-dz/UniFAR-FTUs huggingface dataset:
Association Between Socio-Demographic and Health Functioning Variables Among Patients with Opioid Use Disorder Introduced by Prescription: A Prospective Cohort Study.

BACKGROUND Prescription opioid misuse in Canada has become a serious public health concern and has contributed to Canada's opioid crisis. There are thousands of Canadians who are currently receiving treatment for opioid use disorder, which is a chronic relapsing disorder with enormous impact on individuals and society. OBJECTIVES The aim of this study was to compare the clinical and demographic differences between cohorts of patients who were introduced to opioids through a prescription and those introduced to opioids for non-medical purposes. STUDY DESIGN This was an observational, prospective cohort study. SETTING The study took place in 19 Canadian Addiction Treatment Centres across Ontario. METHODS We included a total of 976 participants who were diagnosed with Opioid Use Disorder and currently receiving methadone maintenance treatment. We excluded participants who were on any other type of prescription opioid or who were missing their 6-month follow-up urine screens. We measured the participants' initial source of introduction to opioids along with other variables using the Maudsley Addiction Profile. We also measured illicit opioid use using urine screens at baseline and at 6-months follow-up. RESULTS Almost half the sample (n = 469) were initiated to opioids via prescription. Women were more likely to be initiated to opioids via a prescription (OR = 1.385, 95% CI 1.027-1.866, P = .033). Those initiated via prescription were also more likely to have post-secondary education, older age of onset of opioid use, less likely to have hepatitis C and less likely to have use cannabis. Chronic pain was significantly associated with initiation to opioids through prescription (OR = 2.720, 95% CI 1.998-3.722, P < .0001). Analyses by gender revealed that men initiated by prescription were less likely to have liver disease and less likely to use cannabis, while women initiated by prescription had a higher methadone dose. LIMITATIONS This project was limited by its study design being observational in nature; no causal relationships can be inferred. Also, the data did not allow determination of the role that the prescribed opioids played in developing opioid use disorder. CONCLUSIONS Our results have revealed that almost half of this methadone maintenance treatment (MMT) population has been introduced to opioids through a prescription. Given that the increasing prescribing rates of opioids has an impact on this at-risk population, alternative treatments for pain should be considered to help decrease this opioid epidemic in Canada. KEY WORDS Opioid use disorder, chronic pain relief, methadone maintenance treatment, prescriptions, male, female.
Peribiliary Glands Are Key in Regeneration of the Human Biliary Epithelium After Severe Bile Duct Injury

Peribiliary glands (PBG) are a source of stem/progenitor cells organized in a cellular network encircling large bile ducts. Severe cholangiopathy with loss of luminal biliary epithelium has been proposed to activate PBG, resulting in cell proliferation and differentiation to restore biliary epithelial integrity. However, formal evidence for this concept in human livers is lacking. We therefore developed an ex vivo model using precision‐cut slices of extrahepatic human bile ducts obtained from discarded donor livers, providing an intact anatomical organization of cell structures, to study spatiotemporal differentiation and migration of PBG cells after severe biliary injury. Postischemic bile duct slices were incubated in oxygenated culture medium for up to a week. At baseline, severe tissue injury was evident with loss of luminal epithelial lining and mural stroma necrosis. In contrast, PBG remained relatively well preserved and different reactions of PBG were noted, including PBG dilatation, cell proliferation, and maturation. Proliferation of PBG cells increased after 24 hours of oxygenated incubation, reaching a peak after 72 hours. Proliferation of PBG cells was paralleled by a reduction in PBG apoptosis and differentiation from a primitive and pluripotent (homeobox protein Nanog+/ sex‐determining region Y‐box 9+) to a mature (cystic fibrosis transmembrane conductance regulator+/secretin receptor+) and activated phenotype (increased expression of hypoxia‐inducible factor 1 alpha, glucose transporter 1, and vascular endothelial growth factor A). Migration of proliferating PBG cells in our ex vivo model was unorganized, but resulted in generation of epithelial monolayers at stromal surfaces. Conclusion: Human PBG contain biliary progenitor cells and are able to respond to bile duct epithelial loss with proliferation, differentiation, and maturation to restore epithelial integrity. The ex vivo spatiotemporal behavior of human PBG cells provides evidence for a pivotal role of PBG in biliary regeneration after severe injury.
Finding Tutte paths in linear time

It is well-known that every 2-connected planar graph has a Tutte path, i.e., a path P such that any component of G-P has only two or three attachment points on P. However, it was only recently shown that such Tutte paths can be found in polynomial time. In this paper, we give a new proof that 2-connected planar graphs have Tutte paths which leads easily to a linear-time algorithm to find Tutte paths. Furthermore, for 3-connected planar graphs our Tutte paths come with a system of distinct representatives, a strengthening that allows applications (such as finding 2-walks) to also be done in linear time.
Extremely sensitive and wide-range silver ion detection via assessing the integrated surface potential of a DNA-capped gold nanoparticle

With the rapid development of nanotechnology and its associated waste stream, public concern is growing over the potential toxicity exposure to heavy metal ions poses to the human body and the environment. Herein, we report an extremely sensitive Kelvin probe force microscopy (KPFM)-based platform for detecting nanotoxic materials (e.g. Ag+) accomplished by probing the integrated surface potential differences of a single gold nanoparticle on which an interaction between probe DNA and target DNA occurs. This interaction can amplify the surface potential of the nanoparticle owing to the coordination bond mediated by Ag+ (cytosine–Ag+–cytosine base pairs). Interestingly, compared with conventional methods, this platform is capable of extremely sensitive Ag+ detection (∼1 fM) in a remarkably wide-range (1 fM to 1 μM). Furthermore, this platform enables Ag+ detection in a practical sample (general drinking water), and this KPFM-based technique may have the potential to detect other toxic heavy metal ions and single nucleotide polymorphisms by designing specific DNA sequences.
Genomic Characteristics of Invasive Mucinous Adenocarcinomas of the Lung and Potential Therapeutic Targets of B7-H3

Pulmonary invasive mucinous adenocarcinoma (IMA) is considered a variant of lung adenocarcinomas based on the current World Health Organization classification of lung tumors. However, the molecular mechanism driving IMA development and progression is not well understood. Thus, we surveyed the genomic characteristics of IMA in association with immune-checkpoint expression to investigate new potential therapeutic strategies. Tumor cells were collected from surgical specimens of primary IMA, and sequenced to survey 53 genes associated with lung cancer. The mutational profiles thus obtained were compared in silico to conventional adenocarcinomas and other histologic carcinomas, thereby establishing the genomic clustering of lung cancers. Immunostaining was also performed to compare expression of programmed death ligand 1 (PD-L1) and B7-H3 in IMA and conventional adenocarcinomas. Mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS) were detected in 75% of IMAs, but in only 11.6% of conventional adenocarcinomas. On the other hand, the frequency of mutations in epidermal growth factor receptor (EGFR) and tumor protein p53 (TP53) genes was 5% and 10%, respectively, in the former, but 48.8% and 34.9%, respectively, in the latter. Clustering of all 78 lung cancers indicated that IMA is distinct from conventional adenocarcinoma or squamous cell carcinoma. Strikingly, expression of PD-L1 in ≥1% of cells was observed in only 6.1% of IMAs, but in 59.7% of conventional adenocarcinomas. Finally, 42.4% and 19.4% of IMAs and conventional adenocarcinomas, respectively, tested positive for B7-H3. Although currently classified as a variant of lung adenocarcinoma, it is also reasonable to consider IMA as fundamentally distinct, based on mutation profiles and genetic clustering as well as immune-checkpoint status. The immunohistochemistry data suggest that B7-H3 may be a new and promising therapeutic target for immune checkpoint therapy.
The Effects of Substance Abuse on Blood Glucose Parameters in Patients with Diabetes: A Systematic Review and Meta-Analysis

Background: People who abuse substances are at increased risk of metabolic syndrome and diabetes resulting partly from increased cell damage and due to the effects of opioids on glucose homeostasis. Therefore, people with diabetes who abuse substances may carry greater health risks than the general population resulting from their effect on glucose metabolism. These substances may be in the form of cannabis, hallucinogens, opioids, and stimulants. Therefore, the aim of this review was to evaluate the effects of substance abuse on blood glucose parameters in patients with diabetes. Method: Databases including Embase, Psycho-Info, Google Scholar and PubMed were searched systematically for relevant articles from database inception to May 2018. Search terms including medical subject headings (MeSH) based on the Population, Intervention, Comparator and Outcomes (PICO) framework was used to access the databases. Eligible articles were selected based on set inclusion and exclusion criteria. The articles reviewed were evaluated for quality and meta-analysis and sensitivity analysis were carried out using the Review Manager (RevMan 5.3, The Cochrane Collaboration, Copenhagen, Denmark). The Random effects model was used for the data analysis. Results: Twelve studies which met the inclusion criteria were included in the systematic review, while nine articles were selected for the meta-analysis. The results of the meta-analysis showed that substance abuse does not have significant effects (p > 0.05) on postprandial blood glucose and glycated haemoglobin in patients with diabetes. With respect to the effect of substance abuse on fasting blood glucose, while this was significant (p < 0.05) following meta-analysis, the results of the sensitivity test did not demonstrate any significant difference (p > 0.05) between patients who abused substances compared with control. This would suggest that the effect of substance abuse on fasting blood glucose in these patients was not very reliable or not consistent. Conclusions: The effect of substance abuse on glycated haemoglobin and postprandial blood glucose in patients with diabetes was not significant. In the meta-analysis, while the value was slightly lower with respect to postprandial blood glucose, this was slightly higher in relation to HbA1c in the substance abuse group compared with control. On the other hand, the effect of substance abuse on fasting blood glucose was significant (p = 0.03) compared with control, but this was attenuated following a sensitivity test. A range of factors including eating habits, characteristics of drugs, erratic lifestyle of patients may explain the outcome of this review. There is the need for randomised controlled trials that will include diet and medication history in order to fully understand the effect of substance abuse on blood glucose parameters in patients with diabetes.
Into the Wild: The Challenges of Physiological Stress Detection in Laboratory and Ambulatory Settings

Stress and mental health have become major concerns worldwide. Research has already extensively investigated physiological signals as quantitative and continuous markers of stress. In recent years, the focus of the field has shifted from the laboratory to the ambulatory environment. We provide an overview of physiological stress detection in laboratory settings with a focus on identifying physiological sensing priorities, including electrocardiogram, skin conductance, and electromyogram, and the most suitable machine learning techniques, of which the choice depends on the context of the application. Additionally, an overview is given of new challenges ahead to move toward the ambulant environment, including the influence of physical activity, lower signal quality due to motion artifacts, the lack of a stress reference, and the subject-dependent nature of the physiological stress response. Finally, several recommendations for future research are listed, focusing on large-scale, longitudinal trials across different population groups and just-in-time interventions to move toward disease prevention and interception.
Catheter Ablation for Atrial Fibrillation with Heart Failure.

To the Editor: In the Catheter Ablation versus Standard Conventional Therapy in Patients with Left Ventricular Dysfunction and Atrial Fibrillation (CASTLE-AF) trial, Marrouche et al. (Feb. 1 issue)1 found a 46% lower rate of death from any cause among patients who were randomly assigned to catheter ablation than among those who were assigned to medical therapy. One concern in interpreting these results is that the patients underwent randomization before the run-in phase.2,3 During the run-in phase, 18 patients in the ablation group and 9 in the medical-therapy group were excluded. This process may have affected patient assignments and subverted randomization. Consequent imbalances that may have had an effect on the primary end point include a significantly higher proportion of patients in the medical-therapy group than in the ablation group who had a diagnosis of ischemic cardiomyopathy, who had diabetes mellitus, and who were receiving digoxin at baseline. Ischemic heart disease, diabetes, and a high serum digoxin concentration have all been associated with increased mortality, and no data regarding digoxin dosing or monitoring were reported in the article.4,5 Although ischemic heart disease and digoxin therapy are known confounding factors, the possibility of imbalances of unknown confounding factors cannot be ruled out.
Functions of pointing by humans, and dogs’ responses, during dog-human play between familiar and unfamiliar players

Although much research focuses on human index finger pointing to hidden items for dogs in experimental settings, there is little research about human pointing in naturalistic interactions. We examined human pointing to dogs during 62 dog-human play interactions, spanning 4.8 hours of videotape, to determine the functions of human pointing and dogs’ responses to that pointing. Participants were 26 humans and 27 dogs. Humans played with their own dog(s) and, almost always, an unfamiliar dog. Seventeen people (16 players and one passerby) pointed for 20 dogs a total of 101 times (once with a foot) during 26 interactions. Most (49.5%) points were toward an object (almost always a ball), to direct attention or action toward the object; 36.6% were to the ground in front of the (almost always familiar) pointer, directing the dog to come, and/or drop a ball the dog held, here; 10.9% directed the dog toward the designated player and/or play area; and 3.0% directed the dog to move away from a ball the dog had dropped. Humans almost always pointed such that the dog could see the point (92.1%), and pointed more with their own than with an unfamiliar dog. Dogs responded appropriately (i.e., did what the pointer requested) for only 24.7% of the visible points, more often for points to the ground than for points to objects. The proportion of dogs’ appropriate responses to visible points was similar for both familiar (30%) and unfamiliar (18%) humans. Six dogs who responded appropriately to some points resisted responding appropriately to others. Future research should examine non-object directed uses of pointing with dogs and their responses in naturalistic and experimental settings, and experimentally assess diverse explanations, including resistance, when dogs and other animals fail standard pointing tasks.
Response to Ghinolfi et al.

The authors welcome the discourse presented by Ghinolfi et al. [1] and appreciate the opportunity to respond to their comments on the manuscript "Association between donor age and risk of graft failure after liver transplantation: an analysis of the Eurotransplant database" [2]. The aim of our study was to estimate the effect of donor age on the risk of graft failure in liver transplantation. This article is protected by copyright. All rights reserved.
Morphological and Molecular Variation Between Fusarium avenaceum, Fusarium arthrosporioides and Fusarium anguioides Strains

Fusarium avenaceum and closely related species are common fungi on various plants, cultivated in different climatic regions. The aim of this study was to determine the taxonomic affiliations of the F. avenaceum, Fusarium arthrosporioides, and Fusarium anguioides strains by using morphological, physiological and molecular-genetic approaches. Twenty-six single-spored morphologically identified strains, which were mainly from cereals, were investigated in order to find out, if they belong to a separate species. Pathogenicity of strains to wheat seedlings and ISSR (Inter Simple Sequence Repeats) fingerprint and beta-tubulin DNA sequence patterns were analyzed. According to phylogenetic analyses, the strains could be divided into two big groups consisting of mostly F. avenaceum or F. anguioides strains. F. arthrosporioides was not detected as a separate species by the sum of the characters. F. anguioides was characterized as a separate species, which could be identified by morphological and molecular data. High genetic diversity of the F. avenaceum and related species was revealed. One F. anguioides strain (rudbeckia, Vladivostok, Russia), had an identical beta-tubulin sequence with two previously sequenced strains of Fusarium tricinctum species complex, which were isolated from dicotyledonous plants in Asia.
INLI@FIRE-2018: A Native Language Identification System using Convolutional Neural Networks

Native Language Identification is the problem of identifying the first language of speakers based on his/her writings in another language. The proposed approach is a deep learning based methodology using convolutional neural networks. Convolutional neural networks are a class of neural networks that have proven very effective in areas such as pattern recognition and classification. They are able to capture the local texture within the text and can be used to find the representative patterns in a text document. The proposed system consists of a language identification model, which is trained by a corpus of 1233 documents. The experiments were conducted using the dataset provided for INLI@FIRE2018. The results indicate that the system is capable of giving performance comparable to the methods employing more sophisticated approaches.
Methylation of BNIP3 in pancreatic cancer inhibits the induction of mitochondrial-mediated tumor cell apoptosis

Bcl-2 interacting protein 3 (BNIP3) is involved in various cellular processes and is considered a key regulator of hypoxia-induced apoptosis. In the present study, the expression of BNIP3 in pancreatic cancer tissues, the correlation with clinicopathological characteristics and prognosis and the regulation of this protein in pancreatic cancer cell lines with regard to the induction of apoptosis were investigated. BNIP3 expression was significantly lower in pancreatic cancer tissues compared with normal epithelia and was associated with tumor size, clinical stage, and lymph node metastasis. The expression of BNIP3 correlated positively to the proapoptotic protein Bax and negatively to the antiapoptotic protein Bcl-2, whereas the induction of apoptosis by BNIP3 was independent of caspase 3 and 9 activation. The restoration of BNIP3 expression in pancreatic cancer cells in vitro, caused loss of ΔΨm, increase in ROS production, and apoptosis induction. The opposite effect was observed in pancreatic cancer cells, following BNIP3 silencing by RNAi. The absence of BNIP3 expression in pancreatic cancer cells was related to gene methylation that suppressed binding of HIF-1α to the BNIP3 promoter, whereas 5-Aza-2′-deoxycytidine (Aza-dC) treatment restored BNIP3 expression and sensitized pancreatic cancer cells to BNIP3-induced apoptosis. The findings indicated that BNIP3 was significantly downregulated in pancreatic cancer resulting in reduced apoptosis induction. Silencing of BNIP3 expression was associated with methylation of the hypoxia-responsive element (HRE) site that in turn inhibited the binding of HIF-1α to the BNIP3 promoter. The data suggest that BNIP3 reactivation is a potential target for therapeutic intervention against pancreatic cancer.
Drebrin-like (Dbnl) Controls Neuronal Migration via Regulating N-Cadherin Expression in the Developing Cerebral Cortex

The actin cytoskeleton is crucial for neuronal migration in the mammalian developing cerebral cortex. The adaptor protein Drebrin-like (Dbnl) plays important roles in reorganization of the actin cytoskeleton, dendrite formation, and endocytosis by interacting with F-actin, cobl, and dynamin. Although Dbnl is known to be expressed in the brain, the functions of this molecule during brain development are largely unknown. In this study, to examine the roles of Dbnl in the developing cerebral cortex, we conducted experiments using mice of both sexes with knockdown of Dbnl, effected by in utero electroporation, in the migrating neurons of the embryonic cortex. Time-lapse imaging of the Dbnl-knockdown neurons revealed that the presence of Dbnl is a prerequisite for appropriate formation of processes in the multipolar neurons in the multipolar cell accumulation zone or the deep part of the subventricular zone, and for neuronal polarization and entry into the cortical plate. We found that Dbnl knockdown decreased the amount of N-cadherin protein expressed on the plasma membrane of the cortical neurons. The defect in neuronal migration caused by Dbnl knockdown was rescued by moderate overexpression of N-cadherin and αN-catenin or by transfection of the phospho-mimic form (Y337E, Y347E), but not the phospho-resistant form (Y337F, Y347F), of Dbnl. These results suggest that Dbnl controls neuronal migration, neuronal multipolar morphology, and cell polarity in the developing cerebral cortex via regulating N-cadherin expression. SIGNIFICANCE STATEMENT Disruption of neuronal migration can cause neuronal disorders, such as lissencephaly and subcortical band heterotopia. During cerebral cortical development, the actin cytoskeleton plays a key role in neuronal migration; however, the mechanisms of regulation of neuronal migration by the actin cytoskeleton still remain unclear. Herein, we report that the novel protein Dbnl, an actin-binding protein, controls multiple events during neuronal migration in the developing mouse cerebral cortex. We also showed that this regulation is mediated by phosphorylation of Dbnl at tyrosine residues 337 and 347 and αN-catenin/N-cadherin, suggesting that the Dbnl-αN-catenin/N-cadherin pathway is important for neuronal migration in the developing cortex.