Miracle-dz/UniFAR-FTUs huggingface dataset:
The Clinical Impact of GLP-1 Receptor Agonists in Type 2 Diabetes : Focus on the Long-Acting Analogs

GLP-1 receptor agonists (GLP-1 RAs), introduced for clinical use in 2005, have excellent potency in reducing HbA1c and mean glucose, improving fasting plasma glucose, inducing weight loss or protecting against the weight gain associated with insulin therapy, reducing appetite, and delaying gastric emptying. Two of these medications, liraglutide and semaglutide, appear to have cardioprotective effects as reflected in cardiovascular outcomes studies. The GLP-1 RAs are associated with gastrointestinal side effects that tend to diminish over time. They have very low risk of hypoglycemia unless used in conjunction with insulin or insulin secretagogues. Two coformulations of GLP-1 RAs together with long-acting basal insulin are available for daily use. The original GLP-1 RA, exenatide, requires twice-daily injections; two short-acting analogs are given once daily. Three currently available long-acting GLP-1 RAs are injected once weekly, providing greater convenience and potentially improving patient adherence. Semaglutide appears to be the most effective in terms of HbA1c reduction and weight loss. GLP-1 RAs can be combined with all classes of antihyperglycemic agents except DPP-4 inhibitors. Current studies are exploring the use of an implantable osmotic pump for long-term administration of a rapid acting analog (exenatide), an oral preparation of semaglutide, benefits for management of obesity and nonalcoholic steatohepatitis, and mechanisms of cardioprotective effects.
Function, dynamics and evolution of network motif modules in integrated gene regulatory networks of worm and plant

Abstract Gene regulatory networks (GRNs) consist of different molecular interactions that closely work together to establish proper gene expression in time and space. Especially in higher eukaryotes, many questions remain on how these interactions collectively coordinate gene regulation. We study high quality GRNs consisting of undirected protein–protein, genetic and homologous interactions, and directed protein–DNA, regulatory and miRNA–mRNA interactions in the worm Caenorhabditis elegans and the plant Arabidopsis thaliana. Our data-integration framework integrates interactions in composite network motifs, clusters these in biologically relevant, higher-order topological network motif modules, overlays these with gene expression profiles and discovers novel connections between modules and regulators. Similar modules exist in the integrated GRNs of worm and plant. We show how experimental or computational methodologies underlying a certain data type impact network topology. Through phylogenetic decomposition, we found that proteins of worm and plant tend to functionally interact with proteins of a similar age, while at the regulatory level TFs favor same age, but also older target genes. Despite some influence of the duplication mode difference, we also observe at the motif and module level for both species a preference for age homogeneity for undirected and age heterogeneity for directed interactions. This leads to a model where novel genes are added together to the GRNs in a specific biological functional context, regulated by one or more TFs that also target older genes in the GRNs. Overall, we detected topological, functional and evolutionary properties of GRNs that are potentially universal in all species.
Identifying Groundwater Recharge Sites through Environmental Stable Isotopes in an Alluvial Aquifer

Environmental isotope tracers have been a useful tool in providing new insights into hydrologic processes. In Mexico, there have been several studies reporting different values for δ 18 O and δ 2 H for certain geographical areas. The objective of this study is to achieve the isotopic characterization of rainfall and groundwater and to report the comprehensive understanding of groundwater flow processes around and within the Calera aquifer and, consequently, its potential recharge sites. The samples used for the stable isotope analysis ( δ 18 O , δ 2 H ) were measured using a GV-Isoprime isotope-ratio mass spectrometer at the Isotopy Laboratory of the Water Center for Latin America and the Caribbean. The δ D of precipitation ranged between −110.20‰ and 10.11‰, with a mean of −55.67‰ ± 27.81‰. The δ 18 O ranged between −17.80‰ and 2.74‰, with a mean of −9.44‰ ± 4.74‰. The δ D of groundwater ranged between −81.92‰ and −36.45‰, with a mean of −66.05‰ ± 8.58‰. The δ 18 O ranged between −18.26‰ and −8.84‰, with a mean of −12.35‰ ± 2.12‰. The local meteoric water line of the Zacatecas state is δ D = − 2.03 + 5.68 δ 18 O . The groundwater samples were clustered into four groups. The clustering of the samples led to the finding that streamflows play a significant role in the hydrological balance as a source of local recharge to the aquifer.
Sampling Social Media: Supporting Information Retrieval from Microblog Data Resellers with Text, Network, and Spatial Analysis

This paper presents a computationally assisted method for scaling researcher expertise to large, online social media datasets in which access is constrained and costly. Developed collaboratively between social and computer science researchers, this method is designed to be flexible, scalable, cost-effective, and to reduce bias in data collection. Online response to six case studies covering elections and election-related violence in Sub-Saharan African countries are explored using Twitter, a popular online microblogging platform. Results show: 1) automated query expansion can mitigate researcher bias, 2) machine learning models combining textual, social, temporal, and geographic features in social media data perform well in filtering data unrelated to the target event, and 3) these results are achievable while minimizing fee-based queries by bootstrapping with readily-available Twitter samples.
The Making of a 'Top' Open Data City: A Case Study of Edmonton's Open Data Initiative

In recent years, various models and indexes have been proposed to evaluate and rate the performance of open data initiatives. However, little research examines cities’ open data initiatives in relation to these indexes and how cities achieve open data success. Through an exploratory case study of Edmonton, Canada’s top ranked open data city, this research sheds light on the mechanisms contributing to top-rated and successful open data initiatives. Our findings reveal current open data indexes emphasize publication of data sets over the measurement of impact. The case study suggests that to be successful, cities should approach open data as a continuing journey and must actively engage other stakeholders, particularly intermediaries and citizens. Finally, we observe that common myths constructed around open data help promote open data at a strategic level, but must be viewed skeptically at the operational level.
On the Importance of Considering Country-specific Aspects on the Online-Market: An Example of Music Recommendation Considering Country-Specific Mainstream

In the field of music recommender systems, country-specific aspects have received little attention, although it is known that music perception and preferences are shaped by culture; and culture varies across countries. Based on the LFM-1b dataset (including 53,258 users from 47 countries), we show that there are significant country-specific differences in listeners’ music consumption behavior with respect to the most popular artists listened to. Results indicate that, for instance, Finnish users’ listening behavior is farther away from the global mainstream, while United States’ listeners are close to the global mainstream. Relying on rating prediction experiments, we tailor recommendations to a user’s level of preference for mainstream (defined on a global level and on a country level) and the user’s country. Results suggest that, in terms of rating prediction accuracy, a combination of these two filtering strategies works particularly well for users of countries far away from the global mainstream.
Differences in the Reasons of Intermittent versus Permanent Discontinuance in Social Media: An Exploratory Study in Weibo

Discontinued usage (or discontinuance) of social media has aroused extensive interests among researchers and practitioners. Existing research tends to view discontinuance as permanent, but pays little attention to intermittent discontinuance wherein individuals stop using a social medium for a certain period of time but eventually restart using afterwards. Specifically, little is known about the commonalities and differences in reasons underlying permanent and intermittent discontinuance. Addressing this research gap, this paper reports an exploratory field study using qualitative data collected by interviewing 96 users with discontinuance experiences in Weibo, a popular Chinese microblogging platform. Results reveal four categories of reasons for discontinuance: user-, context-, functionand content-related. Comparative analysis shows that user discontinuance because of context-related factors is more likely to be intermittent, while user discontinuance due to functionand content-related factors are more likely to be permanent; results for user-related factors are complicated. Theoretical and practical implications are discussed.
Dairy food consumption is associated with a lower risk of the metabolic syndrome and its components: a systematic review and meta-analysis

Abstract A systematic review and a meta-analysis of observational studies were performed to assess the dose–response relationship between specific types of dairy foods and the risk of the metabolic syndrome (MetS) and its components. Studies of dairy foods and the risk of the MetS and its components published up to June 2016 were searched using PubMed, EMBASE and a reference search. Random-effects models were used to estimate the pooled relative risks (RR) with 95 % CI. Finally, ten cross-sectional studies, two nested case–control studies and twenty-nine cohort studies were included for the analysis. In a dose–response analysis of cohort studies and cross-sectional studies, the pooled RR of the MetS for a one-serving/d increment of total dairy food (nine studies) and milk (six studies) consumption (200 g/d) were 0·91 (95 % CI 0·85, 0·96) and 0·87 (95 % CI 0·79, 0·95), respectively. The pooled RR of the MetS for yogurt (three studies) consumption (100 g/d) was 0·82 (95 % CI 0·73, 0·91). Total dairy food consumption was associated with lower risk of MetS components, such as hyperglycaemia, elevated blood pressure, hypertriacylglycerolaemia and low HDL- cholesterol. A one-serving/d increment of milk was related to a 12 % lower risk of abdominal obesity, and a one-serving/d increment of yogurt was associated with a 16 % lower risk of hyperglycaemia. These associations were not significantly different by study design, study location or adjustment factors. This meta-analysis showed that specific types of dairy food consumption such as milk and yogurt as well as total dairy food consumption were inversely related to risk of the MetS and its components.
Does a plant‐eating insect's diet govern the evolution of insecticide resistance? Comparative tests of the pre‐adaptation hypothesis

According to the pre‐adaptation hypothesis, the evolution of insecticide resistance in plant‐eating insects co‐opts adaptations that initially evolved during chemical warfare with their host plants. Here, we used comparative statistics to test two predictions of this hypothesis: (i) Insects with more diverse diets should evolve resistance to more diverse insecticides. (ii) Feeding on host plants with strong or diverse qualitative chemical defenses should prime an insect lineage to evolve insecticide resistance. Both predictions are supported by our tests. What makes this especially noteworthy is that differences in the diets of plant‐eating insect species are typically ignored by the population genetic models we use to make predictions about insecticide resistance evolution. Those models surely capture some of the differences between host‐use generalists and specialists, for example, differences in population size and migration rates into treated fields, but they miss other potentially important differences, for example, differences in metabolic diversity and gene expression plasticity. Ignoring these differences could be costly.
Mining for meaning: from vision to language through multiple networks consensus

Describing visual data into natural language is a very challenging task, at the intersection of computer vision, natural language processing and machine learning. Language goes well beyond the description of physical objects and their interactions and can convey the same abstract idea in many ways. It is both about content at the highest semantic level as well as about fluent form. Here we propose an approach to describe videos in natural language by reaching a consensus among multiple encoder-decoder networks. Finding such a consensual linguistic description, which shares common properties with a larger group, has a better chance to convey the correct meaning. We propose and train several network architectures and use different types of image, audio and video features. Each model produces its own description of the input video and the best one is chosen through an efficient, two-phase consensus process. We demonstrate the strength of our approach by obtaining state of the art results on the challenging MSR-VTT dataset.
Engineering of a rough auxotrophic mutant Salmonella Typhimurium for effective delivery

Live Salmonella vaccine vectors offer a remarkable platform for delivering immunogens and therapeutic molecules by mimicking natural intracellular infections; however, pre-existing anti-vector immunity can impede effective deployment. Measures to alleviate pre-existing immunity include the use of heterologous vectors, development of highly attenuated strain enabling greater payload, removal of major immunoreactive components from the vector, and/or augmentation of delivered antigens via increased presentation in antigen presenting cells. Here we report a Salmonella Typhimurium (ST) vector-JOL1800 that embodies these requisite properties. JOL1800 is a highly attenuated, auxotrophic, and O-antigen deficient rough-mutant strain. Heterologous bacterial and viral antigens were expressed and delivered using JOL1800 in mice, irrespective of the inoculation route successful inductions of the mucosal and systemic humoral responses were observed. Compared to smooth LPS vector delivery, we observed an increased fraction of delivered-antigen presenting dendritic cells and a higher frequency of delivered-antigen displayed per macrophage. Upon post-priming with JOL1800 delivery, efficacy of the delivery was minimally affected as indicated by insignificant decrease in colonization, humoral and cellular responses. Our results show that the generated vector is capable of remote antigen delivery, manifests higher antigen presentation, is Differentiating Infected from Vaccinated Animals (DIVA) capable, evades normal pre-existing immunity, and can be deployed for effective delivery.
Understanding code quality for introductory courses

An exploration of the meaning of ‘code quality’ for introductory programming courses has led to a model that brings together teacher feedback and suggestions from professional handbooks. We translated this model into a rubric for giving feedback to students in their first courses. Using this rubric in teaching has encouraged us to reflect on the intent of programming language features and how these can be used appropriately. We now propose future work: how can ‘approriate use’ be more systematically integrated into the model? Furthermore, we propose that using the derived rubric in teaching may very well confront students with unnoticed misconceptions and help them eliminate these. Is this a reasonable assumption? How can we test it?
Genetic Analysis of Rare Human Variants of Regulators of G Protein Signaling Proteins and Their Role in Human Physiology and Disease

Regulators of G protein signaling (RGS) proteins modulate the physiologic actions of many neurotransmitters, hormones, and other signaling molecules. Human RGS proteins comprise a family of 20 canonical proteins that bind directly to G protein–coupled receptors/G protein complexes to limit the lifetime of their signaling events, which regulate all aspects of cell and organ physiology. Genetic variations account for diverse human traits and individual predispositions to disease. RGS proteins contribute to many complex polygenic human traits and pathologies such as hypertension, atherosclerosis, schizophrenia, depression, addiction, cancers, and many others. Recent analysis indicates that most human diseases are due to extremely rare genetic variants. In this study, we summarize physiologic roles for RGS proteins and links to human diseases/traits and report rare variants found within each human RGS protein exome sequence derived from global population studies. Each RGS sequence is analyzed using recently described bioinformatics and proteomic tools for measures of missense tolerance ratio paired with combined annotation-dependent depletion scores, and protein post-translational modification (PTM) alignment cluster analysis. We highlight selected variants within the well-studied RGS domain that likely disrupt RGS protein functions and provide comprehensive variant and PTM data for each RGS protein for future study. We propose that rare variants in functionally sensitive regions of RGS proteins confer profound change-of-function phenotypes that may contribute, in newly appreciated ways, to complex human diseases and/or traits. This information provides investigators with a valuable database to explore variation in RGS protein function, and for targeting RGS proteins as future therapeutic targets.
IoTChain: A Three-Tier Blockchain-based IoT Security Architecture

There has been increasing interest in the potential of blockchain in enhancing the security of devices and systems, such as Internet of Things (IoT). In this paper, we present a blockchain-based IoT security architecture, IoTchain. The three-tier architecture comprises an authentication layer, a blockchain layer and an application layer, and is designed to achieve identity authentication, access control, privacy protection, lightweight feature, regional node fault tolerance, denial-of-service resilience, and storage integrity. We also evaluate the performance of IoTchain to demonstrate its utility in an IoT deployment.
Successful Feasibility Human Trial of a New Self-Expandable Percutaneous Pulmonary Valve (Pulsta Valve) Implantation Using Knitted Nitinol Wire Backbone and Trileaflet &agr;-Gal–Free Porcine Pericardial Valve in the Native Right Ventricular Outflow Tract

Background— Self-expandable percutaneous pulmonary valve implantation (PPVI) for native right ventricular outflow tract lesions is still in the clinical trial phase. The aim of this study is to present the result of feasibility study of a novel self-expandable knitted nitinol wire stent mounted with a treated trileaflet &agr;-Gal–free porcine pericardial valve for PPVI. Methods and Results— A feasibility study using Pulsta valve (TaeWoong Medical Co, Gyeonggi-do, South Korea) was designed for patients with severe pulmonary regurgitation in the native right ventricular outflow tract, and 6-month follow-up outcomes were reviewed. Ten tetralogy of Fallot patients were enrolled. Before PPVI, severe pulmonary regurgitation (mean pulmonary regurgitation fraction, 45.5%±7.2%; range, 34.9%–56%) and enlarged right ventricular volume (mean indexed right ventricular end-diastolic volume, 176.7±14.3 mL/m2; range, 158.9–205.9 mL/m2) were present. The median age at PPVI was 21.7±6.5 years (range, 13–36 years). Five patients were successfully implanted with 28 mm and the other 5 with 26 mm valves loaded on the 18F delivery cable. No significant periprocedural complications were noted in any patient. At the 6-month follow-up, indexed right ventricular end-diastolic volume was dramatically decreased to 126.3±20.3 mL/m2 (range, 99–164.2 mL/m2), and the mean value of peak instantaneous pressure gradient between the right ventricle and the pulmonary artery decreased from 6.8±3.5 mm Hg (range, 2–12 mm Hg) before PPVI to 5.7±6.7 mm Hg (range, 2–12 mm Hg) without significant pulmonary regurgitation. There was no adverse event associated with the valve. Conclusions— A feasibility study of the Pulsta valve for native right ventricular outflow tract lesions was completed successfully with planned Pulsta valve implantation and demonstrated good short-term effectiveness without serious adverse events. Clinical Trial Registration— URL: https://www.clinicaltrials. gov. Unique identifier: NCT02555319.
Long-term survival in patients with septic acute kidney injury is strongly influenced by renal recovery

Background Several studies have shown that long-term survival after acute kidney injury (AKI) is reduced even if there is clinical recovery. However, we recently reported that in septic shock patients those that recover from AKI have survival similar to patients without AKI. Here, we studied a cohort with less severe sepsis to examine the effects of AKI on longer-term survival as a function of recovery by discharge. Methods We analyzed patients with community-acquired pneumonia from the Genetic and Inflammatory Markers of Sepsis (GenIMS) cohort. We included patients who developed AKI (KDIGO stages 2–3) and defined renal recovery as alive at hospital discharge with return of SCr to within 150% of baseline without dialysis. Our primary outcome was survival up to 3 years analyzed using Gray’s model. Results Of the 1742 patients who survived to hospital discharge, stage 2–3 AKI occurred in 262 (15%), of which 111 (42.4%) recovered. Compared to recovered patients, patients without recovery were older (75 ±14 vs 69 ±15 years, p<0.001) and were more likely to have at least stage 1 AKI on day 1 (83% vs 52%, p<0.001). Overall, 445 patients (25.5%) died during follow-up, 23.4% (347/1480) for no AKI, 28% (31/111) for AKI with recovery and 44.3% (67/151) for AKI without recovery. Patients who did not recover had worse survival compared to no AKI (HR range 1.05–2.46, p = 0.01), while recovering patients had similar survival compared to no AKI (HR 1.01, 95%CI 0.69–1.47, p = 0.96). Absence of AKI on day 1, no in-hospital renal replacement therapy (RRT), higher Apache III score and higher baseline SCr were associated with recovery after AKI. Conclusions In patients with sepsis, recovery by hospital discharge is associated with long-term survival similar to patients without AKI.
There Is Still No "Fit for All" IS Development Method: Business Development Context and IS Development Characteristics Need to Match

Information systems development has returned to strategic management due to the increase of softwareenabled businesses. We investigated two failed IS development projects using the exploratory case study method. One of the projects was executed with the plan-driven approach methods and the other with the change-driven (agile) approach methods. Data analysis showed that both projects followed the principles of the selected methods. That, however, was not enough. The plan-driven project achieved project objectives but did not deliver business value and the IS was never taken into use. The change-driven project delivered desired business value but failed to release a robust IS. Our main contribution to research is our proposition to match the characteristics of IS development methods with the characteristics of business development contexts. We also disclose some novel reasons for IS project failures.