Miracle-dz/UniFAR-FTUs huggingface dataset:
Identifying mental health and substance use disorders using emergency department and hospital records: a population-based retrospective cohort study of diagnostic concordance and disease attribution

Objectives Administrative data are increasingly being used for surveillance and monitoring of mental health and substance use disorders (MHSUD) across Canada. However, the validity of the diagnostic codes specific to MHSUD is unknown in emergency departments (EDs). Our objective was to determine the concordance, and individual-level and hospital-level factors associated with concordance, between diagnosis codes assigned in ED and at discharge from hospital for MHSUD-related conditions. Design Population-based retrospective cohort study. Setting EDs and hospitals within Vancouver Coastal Health Authority (VCH), British Columbia, Canada. Participants 16 926 individuals who were admitted into a VCH hospital following an ED visit from 1 April 2009 to 31 March 2017, contributing to 48 116 pairs of ED and hospital discharge diagnoses. Primary and secondary outcome measures We examined concordance in identifying MHSUD between the primary discharge diagnosis codes based on the International Statistical Classification of Diseases, 9th and 10th Revisions (Canada) assigned in the ED and those assigned in the hospital among all ED visits resulting in a hospital admission. We calculated the percent overall agreement, positive agreement, negative agreement and Cohen’s kappa coefficient. We performed multiple regression analyses to identify factors independently associated with discordance. Results We found a high level of concordance for broad categories of MH conditions (overall agreement=0.89, positive agreement=0.74 and kappa=0.67), and a fair level of concordance for SUDs (overall agreement=0.89, positive agreement=0.31 and kappa=0.27). SUDs were less likely to be indicated as the primary cause in ED as opposed to in hospital (3.8% vs 11.7%). In multiple regression analyses, ED visits occurring during holidays, weekends and overnight (21:00–8:59 hours) were associated with increased odds of discordance in identifying MH conditions (adjusted OR 1.47, 95% CI 1.11 to 1.93; 1.27, 95% CI 1.16 to 1.40; 1.30, 95% CI 1.19 to 1.42, respectively). Conclusions ED data could be used to improve surveillance and monitoring of MHSUD. Future efforts are needed to improve screening for individuals with MHSUD and subsequently connect them to treatment and follow-up care.
Circulating Tumor DNA Profiling in Small-Cell Lung Cancer Identifies Potentially Targetable Alterations

Purpose: Patients with SCLC rarely undergo biopsies at relapse. When pursued, tissue obtained can be inadequate for molecular testing, posing a challenge in identifying potentially targetable alterations in a clinically meaningful time frame. We examined the feasibility of circulating tumor DNA (ctDNA) testing in identifying potentially targetable alterations in SCLC. Experimental Design: ctDNA test results were prospectively collected from patients with SCLC between 2014 and 2017 and analyzed. ctDNA profiles of SCLC at diagnosis and relapse were also compared. Results: A total of 609 samples collected from 564 patients between 2014 and 2017 were analyzed. The median turnaround time for test results was 14 days. Among patients with data on treatment status, there were 61 samples from 59 patients and 219 samples from 206 patients collected at diagnosis and relapse, respectively. The number of mutations or amplifications detected per sample did not differ by treatment status. Potentially targetable alterations in DNA repair, MAPK and PI3K pathways, and genes such as MYC and ARID1A were identifiable through ctDNA testing. Furthermore, our results support that it may be possible to reconstruct the clonal relationship between detected variants through ctDNA testing. Conclusions: Patients with relapsed SCLC rarely undergo biopsies for molecular testing and often require prompt treatment initiation. ctDNA testing is less invasive and capable of identifying alterations in relapsed disease in a clinically meaningful timeframe. ctDNA testing on an expanded gene panel has the potential to advance our knowledge of the mechanisms underlying treatment resistance in SCLC and aid in the development of novel treatment strategies.
Anatomic site as prognostic marker of pancreatic neuroendocrine tumors: a cohort study.

OBJECTIVE Patients with pancreatic neuroendocrine tumors (PNET) have variable prognosis, even with comparable tumor grade and stage. In the current study we aimed to evaluate the prognostic utility of the intrapancreatic PNET anatomical site. DESIGN Cohort study based on the Surveillance Epidemiology and End-Results database. METHODS Patients diagnosed with nonfunctioning PNET between 2004-2015 were compared by anatomic site for disease-specific mortality and all-cause mortality, using log-rank test and by multivariable cox regression analysis. RESULTS 4171 patients (1,839 women [44.1%], median age strata 60-64 years, range 10-14 to ≥85 years) were included in our analysis. Patients with PNETs located at the head vs. body/tail of the pancreas had comparable tumor diameter, as well as ethnicity, gender and age distributions, but had higher rates of grade III and IV NET (13.2% vs. 6.6%, and 4.4% vs. 1.9%, respectively, p<0.001). NETs located at the head vs. body/tail of pancreas were more likely to be locally advanced (32.2% vs 19.9%) with no difference in distant metastases (36.4% vs. 33.5%, respectively, p<0.001). Patients with NETs of the head vs. body/tail of the pancreas had higher disease-specific mortality risk in univariate (log-rank test, p<0.001) and multivariable analysis (Hazard ratio 1.34, 95% confidence interval 1.10-1.65, p=0.004). Multivariable analysis for all-cause mortality also showed increased risk for patients with pancreatic head vs. body/tail PNET (HR 1.23, p=0.013). CONCLUSIONS PNET anatomical location is associated with the mortality risk, and should be considered as a prognostic factor, and as an additional consideration in directing patients management.
Lupus: the new epidemic

Is systemic lupus erythematosus (SLE) is occurring more frequently now than in decades past? Despite improvements in the identification of patients with SLE, the development of new classification criteria, and the recognition of several biomarkers used alone or in combination, the diagnosis of SLE is still a challenge for clinicians, in particular early in the course of the disease, which makes the recognition of secular trends difficult to ascertain. Lacking a uniform definition of preclinical lupus or incomplete lupus, it is difficult to predict accurately which patients would go on to develop SLE. We will briefly review the classification criteria, early or preclinical SLE, the epidemiology of SLE, antinuclear antibodies-negative SLE, and biomarkers of the disease.
Enhanced agonist residence time, internalization rate and signalling of the GIP receptor variant [E354Q] facilitate receptor desensitization and long‐term impairment of the GIP system

In patients with type 2 diabetes mellitus (T2DM), the insulinotropic action of the GIP system is desensitized, whereas this is not the case for the GLP‐1 system. This has raised an interesting discussion of whether GIP agonists or antagonists are most suitable for future treatment of T2DM together with GLP‐1‐based therapies. Homozygous carriers of the GIP receptor (GIPR) variant, [E354Q], display lower bone mineral density, increased bone fracture risk and slightly increased blood glucose. Here, we present an in‐depth molecular pharmacological phenotyping of GIPR‐[E354Q]. In silico modelling suggested similar interaction of the endogenous agonist GIP(1‐42) to [E354Q] as to GIPR wt. This was supported by homologous competition binding in COS‐7 cells revealing GIPR wt‐like affinities of GIP(1‐42) with Kd values of ~2 nmol/L and wt‐like agonist association rates (Kon). In contrast, the dissociation rates (Koff) were slower, resulting in 25% higher agonist residence time for GIPR‐[E354Q]. Moreover, in Gαs signalling (cAMP production) GIP(1‐42) was ~2‐fold more potent and more efficacious on GIPR‐[E354Q] compared to wt with 17.5% higher basal activity. No difference from GIPR wt was found in the recruitment of β‐arrestin 2, whereas the agonist‐induced internalization rate was 2.1‐ to 2.3‐fold faster for [E354Q]. Together with the previously described impaired recycling of [E354Q], our findings with enhanced signalling and internalization rate possibly explained by an altered ligand‐binding kinetics will lead to receptor desensitization and down‐regulation. This could explain the long‐term functional impairment of the GIP system in bone metabolism and blood sugar maintenance for [E354Q] carriers and may shed light on the desensitization of the insulinotropic action of GIP in patients with T2DM.
A Computer Investigation of the Performance of Virtual Reflectors: Part II — The Effects of Room Conditions

In a companion paper [1] a technique for overcoming acoustic problems resulting from the directional nature of human speech in open stage auditoria by means of virtual reflectors has been proposed. In a following paper [2] the system was applied to a computer model of an open stage auditorium in which there was no background noise and the space was relatively dead. In the current paper the action of the virtual reflector has been systematically investigated in more realistic conditions. It is shown to be capable of functioning in conditions which are more reverberant and in conditions in which background noise is present. In all cases investigated the action of a virtual reflector results in conditions to the rear of the primary source (human speaker) being improved such that they become comparable to conditions at equivalent positions to the front. It has been shown that the STI at the rear of a human speaker in an open stage auditorium with the virtual reflector system in operation does not increase significantly with increasing gain [2]. This is due to the Modulation Transfer Function (MTF's) being determined by the convolution of two impulse responses multiplied by a gain factor and added to a third impulse response. The resulting impulse response will therefore consists of many ‘reflections’ and hence the MTF's (and the STI values that they determine) will be adversely affected. An attempt was made to reduce the number of ‘reflections’ in the resultant impulse response by the use of a super directional microphone in order to improve the MTF's and thus the STI values. The actual improvement observed was very small and hence it would appear that the use of a super directional microphone is not particularly effective in this context.
Akt1 regulates pulmonary fibrosis via modulating IL-13 expression in macrophages

Abstract Idiopathic pulmonary fibrosis is a progressive interstitial pneumonia characterised by fibroblast accumulation, collagen deposition and extracellular matrix (ECM) remodelling. It was reported that Akt1 mediated idiopathic pulmonary fibrosis progression through regulating the apoptosis of alveolar macrophage, while its effect on macrophage-produced cytokines remains largely unknown. In the present study, we first examined the phosphorylation of Akt1 in lung sections from idiopathic pulmonary fibrosis patients by immunohistochemistry before applying a bleomycin-induced idiopathic pulmonary fibrosis model using Akt1−/− mice and Akt1+/+ littermates. The results showed that Akt1 was remarkably up-regulated in idiopathic pulmonary fibrosis patients, while in vivo studies revealed that Akt1-deficient mice had well-preserved alveolar structure and fewer collagens, secreted fewer matrix components, including alpha smooth-muscle actin and fibronectin and survived significantly longer than Akt1+/+ littermates. Additionally, the pro-fibrogenic cytokine IL-13 was down-regulated at least twofold in Akt1−/−mice compared to the Akt1+/+group on d 3 and 7 after bleomycin treatment. Furthermore, it was found that Akt1–/– macrophages displayed down-regulation of IL-13 compared to Akt1+/+ macrophages in which Akt1 was phosphorylated in response to IL-33 stimulation. These findings indicate that Akt1 modulates pulmonary fibrosis through inducing IL-13 production by macrophages, suggesting that targeting Akt1 may simultaneously block the fibrogenic processes of idiopathic pulmonary fibrosis.
Some Applications of Interactive Video in Initial Teacher Training

This paper describes disc‐based interactive video applications in initial teacher training which have arisen out of materials developed under the Interactive Video in Schools Project and Interactive Video in Education Awareness Scheme, sponsored by the Department of Trade and Industry. Interactive video is examined in the context of applications in five types of learning environment; as a presentation system for conventional lecturing or small‐group teaching, as a vehicle for independent student learning, as a resource for students on teaching practice, as an information source and as a surrogate tutor. In each case development work is described and future possibilities are discussed.
RASA1 mosaic mutations in patients with capillary malformation-arteriovenous malformation

Background Capillary malformation-arteriovenous malformation is an autosomal dominant disorder, characterised by capillary malformations and increased risk of fast-flow vascular malformations, caused by loss-of-function mutations in the RASA1 or EPHB4 genes. Around 25% of the patients do not seem to carry a germline mutation in either one of these two genes. Even if other genes could be involved, some individuals may have mutations in the known genes that escaped detection by less sensitive techniques. We tested the hypothesis that mosaic mutations could explain some of previously negative cases. Methods DNA was extracted from peripheral blood lymphocytes, saliva or vascular malformation tissues from four patients. RASA1 and EPHB4 coding regions and exon/intron boundaries were analysed by targeted custom gene panel sequencing. A second panel and/or Sanger sequencing were used to confirm the identified mutations. Results Four distinct mosaic RASA1 mutations, with an allele frequency ranging from 3% to 25%, were identified in four index patients with classical capillary malformation-arteriovenous malformation phenotype. Three mutations were known, one was novel. In one patient, a somatic second hit was also identified. One index case had three affected children, illustrating that the mosaicism was also present in the germline. Conclusion This study shows that RASA1 mosaic mutations can cause capillary malformation-arteriovenous malformation. Thus, highly sensitive sequencing techniques should be considered as diagnostic tools, especially for patients with no family history. Even low-level mosaicism can cause the classical phenotype and increased risk for offspring. In addition, our study further supports the second-hit pathophysiological mechanism to explain the multifocality of vascular lesions in this disorder.
Primary Care Practices' Implementation of Patient-Team Partnership: Findings from EvidenceNOW Southwest

Introduction: Care teams partnering with patients are integral to quality primary care. Effective patient-team partnership recognizes patients' contributions in decision-making and respecting patients' goals and social context. We report practice characteristics associated with greater patient-team partnership scores. Methods: EvidenceNOW Southwest was a multistate initiative to improve cardiovascular care in primary care practices through guideline-concordant aspirin use, blood pressure control, cholesterol management, and smoking cessation. EvidenceNOW Southwest provided 9 months of practice facilitation and information technology support through regular meetings and training to 211 Colorado and New Mexico primary care practices from 2015 to 2017. We analyzed surveys from 97% of participating practices regarding patient-team partnership activities of self-management support, social need assessment, resource linkages, and patient input. We used linear and mixed effects regression modeling to examine relationships between patient-team partnership and practice characteristics. Results: Practice characteristics significantly associated with greater patient-team partnership were using patient registries, medically underserved area designation, multispecialty mix, and using clinical cardiovascular disease management guidelines. Our findings suggest that patient-team partnership implementation in small primary care practices is moderate, with mean practice- and member-level scores of 52 of 100 (range, 0–100) and 71 of 100 (range, 10–100), respectively. Conclusion: Practices can improve efforts to partner with patients to assess social needs, gather meaningful input on practice improvement and patient experience, and offer resource connections. Our findings supplement recent evidence that patient registries and evidence-based guidelines may effectively prevent and manage cardiovascular disease. These strategies may also promote primary care patient-team partnership.
Light-Sheet Microscopy and Its Potential for Understanding Developmental Processes.

The ability to visualize and quantitatively measure dynamic biological processes in vivo and at high spatiotemporal resolution is of fundamental importance to experimental investigations in developmental biology. Light-sheet microscopy is particularly well suited to providing such data, since it offers exceptionally high imaging speed and good spatial resolution while minimizing light-induced damage to the specimen. We review core principles and recent advances in light-sheet microscopy, with a focus on concepts and implementations relevant for applications in developmental biology. We discuss how light-sheet microcopy has helped advance our understanding of developmental processes from single-molecule to whole-organism studies, assess the potential for synergies with other state-of-the-art technologies, and introduce methods for computational image and data analysis. Finally, we explore the future trajectory of light-sheet microscopy, discuss key efforts to disseminate new light-sheet technology, and identify exciting opportunities for further advances. Expected final online publication date for the Annual Review of Cell and Developmental Biology Volume 35 is October 7, 2019. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
An Efficient Approach for Four-Layer Channel Routing in VLSI Design

Channel routing is a key problem in VLSI physical design. The main goal of the channel routing problem is to reduce the area of an IC chip. If we concentrate on reducing track number in channel routing problem then automatically the area of an IC chip will be reduced. Here, we propose a new algorithm to reduce the number of tracks using four layers (two horizontal layers and two vertical layers). To be more specific, through this algorithm we convert a two-layer channel routing problem into a four-layer channel routing problem using VCG of the channel. Next, we show the experimental results and graphical structure of that solution.
Ultrasound Time-Harmonic Elastography of the Aorta: Effect of Age and Hypertension on Aortic Stiffness.

OBJECTIVES The aim of this study was to investigate ultrasound time-harmonic elastography for quantifying aortic stiffness in vivo in the context of aging and arterial hypertension. MATERIALS AND METHODS Seventy-four participants (50 healthy participants and 24 participants with long-standing hypertension) were prospectively included between January 2018 and October 2018, and underwent ultrasound time-harmonic elastography of the upper abdominal aorta. Compound maps of shear-wave speed (SWS) as a surrogate of tissue stiffness were generated from multifrequency wave fields covering the full field-of-view of B-mode ultrasound. Blood pressure and pulse wave velocity were measured beforehand. Interobserver and intraobserver agreement was determined in 30 subjects. Reproducibility of time-harmonic elastography was assessed in subgroups with repeated measurements after 20 minutes and after 6 months. Linear regression analysis, with subsequent age adjustment of SWS obtained, receiver operating characteristic analysis, and intraclass correlation coefficients (ICCs) were used for statistical evaluation. RESULTS Linear regression analysis revealed a significant effect of age on SWS with an increase by 0.024 m/s per year (P < 0.001). Age-adjusted SWS was significantly greater in hypertensives (0.24 m/s; interquartile range [IQR], 0.17-0.40 m/s) than in healthy participants (0.07 m/s; IQR, -0.01 to 0.06 m/s; P < 0.001). A cutoff value of 0.15 m/s was found to differentiate best between groups (area under the receiver operating characteristic curve, 0.966; 95% confidence interval, 0.93-1.0; P < 0.001; 83% sensitivity and 98% specificity). Interobserver and intraobserver variability was excellent (ICC, 0.987 and 0.937, respectively). Reproducibility was excellent in the short term (ICC, 0.968; confidence interval, 0.878-0.992) and good in the long term (ICC, 0.844; confidence interval, 0.491-0.959). CONCLUSIONS Ultrasound time-harmonic elastography of the upper abdominal aorta allows quantification of aortic wall stiffness in vivo and shows significantly higher values in patients with arterial hypertension.
Two Phase Recommendation Algorithm Based on Clustering User Interest and Trust

Recommender systems have been proven to be valuable means for Web online users to cope with the information overload and have become one of the most powerful and popular tools in electronic commerce. We need a method to solve such as what items to buy, what music to listen, or what news to read. The diversification of user interests and untruthfulness of rating data are the important problems of recommendation. In this article, we propose to use two phase recommendation based on user interest and trust ratings that have been given by actors to items. In the paper, we deal with the uncertain user interests by clustering firstly. In the algorithm, we compute the between-class entropy of any two clusters and get the stable classes. Secondly, we construct trust based social networks, and work out the trust scoring, in the class. At last, we provide some evaluation of the algorithms and propose the more improve ideas in the future.
Common Type 2 Diabetes Genetic Risk Variants Improve the Prediction of Gestational Diabetes

Abstract Gestational diabetes mellitus (GDM) is a carbohydrate intolerance that occurs in women during pregnancy. The aims of this study were to develop a model to predict the risk of GDM development using common clinical parameters and selected genetic polymorphisms and to analyse the performance of the model using receiver operator characteristic (ROC) curves. ROC analysis was used to examine whether the evaluation of genetic polymorphisms may enhance the accuracy of GDM prediction in comparison to using common clinical risk factors only. This study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75 g oral glucose tolerance test at 24–28 weeks gestation. The difference between the AUC of ROC curves for the model 1 including only age and BMI and the model 2 also including 8 genetic polymorphisms was highly significant (p=0.0001) in favour of model 2 (0.090±0.023). Moreover, the additional use of 8 genetic polymorphisms may increase both the sensitivity and specificity of GDM prediction by 10%. The results of this study indicate that the use of 8 genetic polymorphisms associated with carbohydrate and lipid metabolism and type 2 diabetes [PTGS2 (COX2) rs6681231, FADS1 rs174550, HNF1B rs4430796, ADIPOQ rs266729, IL18 rs187238, CCL2 rs1024611, HHEX rs5015480 and CDKN2A/2B rs10811661] together with clinical risk factors (BMI and age) may significantly improve the prediction of GDM.