bluuebunny/crossref_metadata_2025_split huggingface dataset:
D-Dimer Measured at Diagnosis of Venous Thromboembolism is Associated with Risk of Major Bleeding
Authors: Johnsen Håkon , Hindberg Kristian , Bjøri Esben , Brodin Ellen , Brækkan Sigrid , Morelli Vânia , Hansen John-Bjarne 
Published: March 2019

AbstractIdentification of patients at risk of major bleeding is pivotal for optimal management of anticoagulant therapy in venous thromboembolism (VTE). Studies have suggested that D-dimer may predict major bleeding during anticoagulation; however, this is scarcely investigated in VTE patients. We aimed to investigate the role of D-dimer, measured at VTE diagnosis, as a predictive biomarker of major bleeding. The study population comprised 555 patients with a first community-acquired VTE (1994–2016), who were identified among participants from the Tromsø study. Major bleeding events were recorded during the first year after VTE and defined according to the criteria of the International Society on Thrombosis and Haemostasis. Cox-regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, and duration of anticoagulant therapy. In total, 29 patients experienced major bleeding (incidence rate: 5.7/100 person-years, 95% CI: 4.0–8.2). The major bleeding risk was highest during the first 3 months, especially in patients with D-dimer ≥8.3 µg/mL (upper 20th percentile), with 28.8 major bleedings/100 person-years (95% CI: 13.7–60.4). Patients with D-dimer ≥8.3 µg/mL had a 2.6-fold (95% CI: 1.1–6.6) higher risk of major bleeding than patients with D-dimer ≤2.3 µg/mL (lower 40th percentile). Major bleeding risk according to D-dimer ≥8.3 versus ≤2.3 µg/mL was particularly pronounced among those with deep vein thrombosis (HR: 4.6, 95% CI: 1.3–16.2) and provoked events (HR: 4.2, 95% CI: 1.0–16.8). In conclusion, our results suggest that D-dimer measured at diagnosis may serve as a predictive biomarker of major bleeding after VTE, especially within the initial 3 months.
Incidence and Outcomes of Severe Anaphylaxis in Paediatric Patients in Atlantic Canada
Authors: Krmpotic Kristina , Weisser Caroline , O'Hanley Alexandra , Soder Christian 
Published: March 2019

AbstractLittle is known about severe anaphylaxis in the pediatric population. In this retrospective cohort study, we aimed to describe the characteristics of children who required admission from an outpatient setting to one of two Pediatric Intensive Care Units in Atlantic Canada with a primary diagnosis of anaphylaxis. During the 10-year study period, there were 12 admissions (58% females) for a population incidence of 2.4 per 100,000 children. Both patients who died were adolescents with a witnessed anaphylaxis event, immediately recognized as such after exposure to a known allergen, with immediate access to epinephrine that was not administered until after cardiorespiratory arrest occurred. This study highlights the high mortality associated with severe anaphylaxis and the ongoing need for education surrounding the early administration of intramuscular epinephrine.
Patient Management Strategies and Long-Term Outcomes in Isolated Distal Deep-Vein Thrombosis versus Proximal Deep-Vein Thrombosis: Findings from XALIA
Authors: Ageno Walter , Mantovani Lorenzo , Haas Sylvia , Kreutz Reinhold , Monje Danja , Schneider Jonas , Bugge Jörg-Peter , Gebel Martin , Turpie Alexander 
Published: March 2019

Background Overall, 30 to 50% of lower-limb deep-vein thrombosis (DVT) cases are isolated distal DVT (IDDVT). The recurrent venous thromboembolism (VTE) risk is unclear, leaving uncertainty over optimal IDDVT treatment. We present data on patients with IDDVT and proximal DVT (PDVT) from the prospective, noninterventional XALIA study of rivaroxaban for acute and extended VTE treatment.
Methods Patients aged ≥18 years scheduled to receive ≥3 months' anticoagulation with rivaroxaban or standard anticoagulation were eligible, with follow-up for ≥12 months. We describe baseline characteristics, management strategies, and incidence proportions of VTE recurrence, major bleeding, and all-cause mortality in patients with IDDVT or PDVT, with or without distal vein involvement.
Findings Overall, 1,004 patients with IDDVT and 3,098 with PDVT were enrolled; 641 (63.8%) and 1,683 (54.3%) received rivaroxaban, respectively. Patients with IDDVT were younger and had lower incidences of renal impairment, cancer, and unprovoked VTE than those with PDVT. On-treatment recurrence incidences for IDDVT versus PDVT were 1.0 versus 2.4% (adjusted hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.29–1.08), and incidences posttreatment cessation were 1.1 versus 2.1% (adjusted HR: 0.65; 95% CI: 0.32–1.35), respectively. On-treatment major bleeding incidences were 0.9 versus 1.4% and mortality was 0.8 versus 2.2%, respectively. Median treatment duration in patients with IDDVT was shorter than in those with PDVT (102 vs. 192 days, respectively).
Interpretation Patients with IDDVT had fewer comorbidities and were more frequently treated with rivaroxaban than those with PDVT. On-treatment and posttreatment recurrences were less frequent in patients with IDDVT.
Trial registration number: NCT01619007.
Two Cases of Pediatric AQP4-Antibody Positive Neuromyelitis Optica Spectrum Disorder Successfully Treated with Tocilizumab
Authors: Breu Markus , Glatter Sarah , Höftberger Romana , Freilinger Michael , Kircher Karl , Kasprian Gregor , Seidl Rainer , Kornek Barbara 
Published: March 2019

AbstractB cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice for long-term immunotherapy in aquaporin-4 (AQP4)-antibody positive neuromyelitis optica spectrum disorder (NMOSD). However, up to 30% of patients suffer from relapses despite complete B cell depletion. In these cases, the IL6 (interleukin-6)-receptor blocking antibody tocilizumab has been suggested as an alternative. We report two female adolescents with AQP4-antibody positive NMOSD who relapsed under rituximab treatment and clinically stabilized after switching to monthly administrations of tocilizumab. Our data suggest that early escalation of therapy with tocilizumab may lead to stabilization of disease activity in pediatric NMOSD patients who relapse under B cell depletion.
Bridging to Action Requires Mixed Methods, Not Only Randomised Control Trials
Authors: Olsen Wendy 
Published: March 2019

AbstractDevelopment evaluation refers to evaluating projects and programmes in development contexts. Some evaluations are too narrow. Narrow within-discipline impact evaluations are weaker than multidisciplinary, mixed-methods evaluations. A two-step process leads toward profoundly better arguments in assessing the impact of a development intervention. The first step is setting out the arena for discussion, including what the various entities are in the social, political, cultural and natural environment surrounding the chosen problem. The second step is that, once this arena has been declared, the project and triangulation of data can be brought to bear upon logical arguments with clear, transparent reasoning leading to a set of conclusions. In this second step, we do need scientific methods such as peer review, data and so on, but, crucially, the impact evaluation process must not rest upon a single data type, such as survey data. It is dangerous and undesirable to have the entire validity of the conclusions resting upon randomised control trials, or even a mixture of data types. Different contributions to knowledge exist within the evaluation process, including the interaction of people during action research, ethnography, case-study methods, process tracing and qualitative methods. The cement holding my argument together is that multiple logics are used (retroductive, deductive, and inductive, in particular). Deductive mathematics should not dominate the evaluation of an intervention, as randomised controlled trials on their own lend themselves to worrying fallacies about causality. I show this using Boolean fuzzy set logic. An indicator of high-quality development evaluation is the use of multiple logics in a transparent way.
Isotopes from fossil coronulid barnacle shells record evidence of migration in multiple Pleistocene whale populations
Authors: Taylor Larry D. , O’Dea Aaron , Bralower Timothy J. , Finnegan Seth 
Published: March 2019

Significance
Migration has long been hypothesized to have played a critical role in baleen whale evolution, but fossil constraints on the history of migration are sparse. Here we provide evidence that the oxygen isotope composition of modern whale barnacle shells reliably records migration pathways. We also analyze fossil whale barnacle shells from three Pleistocene localities and show that they display isotope profiles similar to those of modern specimens. Our results indicate the presence of migration among all three ancient whale populations studied and point to the possibility of reconstructing changes in migratory behaviors from the Pliocene to the present.
Earthquake swarms and slow slip on a sliver fault in the Mexican subduction zone
Authors: Fasola Shannon L. , Brudzinski Michael R. , Holtkamp Stephen G. , Graham Shannon E. , Cabral-Cano Enrique 
Published: March 2019

SignificanceWe provide an interpretation for the interaction of crustal faults, clusters of earthquakes (swarms), and slow slip (a slower form of fault rupture) in southern Mexico. Our observations indicate that swarms and slow slip are occurring on a sliver fault in the overriding plate that allows the oblique plate convergence to be separated into a trench-perpendicular and -parallel motion on the subduction interface and sliver fault, respectively. We propose the sliver fault provides a natural pathway for buoyant fluids attempting to migrate upward after being released from the downgoing plate. Thus, sliver faults could be responsible for the downdip end of the seismogenic zone by creating drier conditions on the subduction interface trenchward of the sliver fault.
Ancient trash mounds unravel urban collapse a century before the end of Byzantine hegemony in the southern Levant
Authors: Bar-Oz Guy , Weissbrod Lior , Erickson-Gini Tali , Tepper Yotam , Malkinson Dan , Benzaquen Mordechay , Langgut Dafna , Dunseth Zachary C. , Butler Don H. , Shahack-Gross Ruth , Roskin Joel , Fuks Daniel , Weiss Ehud , Marom Nimrod , Ktalav Inbar , Blevis Rachel , Zohar Irit , Farhi Yoav , Filatova Anya , Gorin-Rosen Yael , Yan Xin , Boaretto Elisabetta 
Published: March 2019

Significance
Historians have long debated the role of climate in the rise and fall of empires of the 1st millennium CE. Drastic territorial contraction of the Byzantine Empire, societal decline, and beginning of the European Middle Ages have generally been linked to the Islamic conquests of the seventh century. This multidisciplinary archaeological investigation of trash mounds in the Negev Desert establishes the end date of organized trash management in the Byzantine-period city of Elusa and demonstrates urban collapse a century before the Islamic transition. Our findings, taken together with other evidence for Byzantine urban dysfunction, the Justinianic Plague, and recent research on the Late Antique Little Ice Age, flesh out the impact of the sixth century on broad historical trajectories.
Anticipating and designing for policy effectiveness
Authors: Bali Azad Singh , Capano Giliberto , Ramesh M 
Published: March 2019

AbstractThe new design orientation in the policy sciences has placed renewed emphasis on problem-solving and developing effective public policies. In this paper, we contribute to this scholarship by presenting a policy framework on anticipating effective policies. We argue that anticipation – that is, foreseeing the future and preparing for it – must be central to how a policy is designed, executed and assessed. Anticipating policy effectiveness requires a careful understanding of the problem and its root causes, as well as selection and utilization of the most ‘appropriate’ policy instrument(s) to solve it. We consider ‘appropriateness’ along three dimensions – analytical, political and operational – in two different respects: choice of policy tools and the capacity of the implementing agency.
Novel Metabolites Are Associated With Augmentation Index and Pulse Wave Velocity: Findings From the Bogalusa Heart Study
Authors: Li Changwei , He Jiang , Li Shengxu , Chen Wei , Bazzano Lydia , Sun Xiao , Shen Luqi , Liang Lirong , Shen Ye , Gu Xiaoying , Kelly Tanika N 
Published: March 2019

Abstract

BACKGROUND
Metabolomics study may help identify novel mechanisms underlying arterial stiffening.

METHODS
We performed untargeted metabolomics profiling among 1,239 participants of the Bogalusa Heart Study. After quality control, 1,202 metabolites were evaluated for associations with augmentation index (AI) and pulse wave velocity (PWV), using multivariate linear regression adjusting for age, sex, race, education, smoking, drinking, body weight, body height, physical activity, and estimated glomerular filtration rate. Heart rate, blood pressure and antihypertensive medication usage, lipids, and fasting glucose were sequentially adjusted in the sensitivity analyses for significant metabolites. Weighted correlation network analysis was applied to build metabolite networks.

RESULTS
Six novel metabolites were negatively associated with AI, of which, 3-methyl-2-oxobutyrate had the lowest P value and the largest effect size (β = –6.67, P = 5.99 × 10–6). Heart rate contributed to a large proportion (25%–58%) of the association for each metabolite. Twenty-one novel metabolites were identified for PWV, of which, fructose (β = 0.61, P = 6.18 × 10–10) was most significant, and histidine had the largest effect size (β = –1.09, P = 2.51 × 10–7). Blood pressure played a major contribution (9%–54%) to the association for each metabolite. Furthermore, 16 metabolites were associated with arterial stiffness independent of traditional risk factors. Network analysis identified 2 modules associated with both AI and PWV (P &lt; 8.00 × 10–4). One was composed of metabolites from the glycerolipids synthesis and recycling pathway, and the other was involved in valine, leucine, and isoleucine metabolism. One module related to sphingomyelin metabolism was associated with PWV only (P = 0.002).

CONCLUSIONS
This study has identified novel and important metabolites and metabolic networks associated with arterial stiffness.
PgpRules: a decision tree based prediction server for P-glycoprotein substrates and inhibitors
Authors: Wang Pei-Hua , Tu Yi-Shu , Tseng Yufeng J 
Published: March 2019

Abstract

Summary
P-glycoprotein (P-gp) is a member of ABC transporter family that actively pumps xenobiotics out of cells to protect organisms from toxic compounds. P-gp substrates can be easily pumped out of the cells to reduce their absorption; conversely P-gp inhibitors can reduce such pumping activity. Hence, it is crucial to know if a drug is a P-gp substrate or inhibitor in view of pharmacokinetics. Here we present PgpRules, an online P-gp substrate and P-gp inhibitor prediction server with ruled-sets. The two models were built using classification and regression tree algorithm. For each compound uploaded, PgpRules not only predicts whether the compound is a P-gp substrate or a P-gp inhibitor, but also provides the rules containing chemical structural features for further structural optimization.

Availability and implementation
PgpRules is freely accessible at https://pgprules.cmdm.tw/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Graph analysis of fragmented long-read bacterial genome assemblies
Authors: Marijon Pierre , Chikhi Rayan , Varré Jean-Stéphane 
Published: March 2019

Abstract

Motivation
Long-read genome assembly tools are expected to reconstruct bacterial genomes nearly perfectly; however, they still produce fragmented assemblies in some cases. It would be beneficial to understand whether these cases are intrinsically impossible to resolve, or if assemblers are at fault, implying that genomes could be refined or even finished with little to no additional experimental cost.

Results
We propose a set of computational techniques to assist inspection of fragmented bacterial genome assemblies, through careful analysis of assembly graphs. By finding paths of overlapping raw reads between pairs of contigs, we recover potential short-range connections between contigs that were lost during the assembly process. We show that our procedure recovers 45% of missing contig adjacencies in fragmented Canu assemblies, on samples from the NCTC bacterial sequencing project. We also observe that a simple procedure based on enumerating weighted Hamiltonian cycles can suggest likely contig orderings. In our tests, the correct contig order is ranked first in half of the cases and within the top-three predictions in nearly all evaluated cases, providing a direction for finishing fragmented long-read assemblies.

Availability and implementation
https://gitlab.inria.fr/pmarijon/knot .

Supplementary information
Supplementary data are available at Bioinformatics online.
Genome-wide identification of the essential protein-coding genes and long non-coding RNAs for human pan-cancer
Authors: Zhang Yuwei , Tao Yang , Ji Huihui , Li Wei , Guo Xingli , Ng Derry Minyao , Haleem Maria , Xi Yang , Dong Changzheng , Zhao Jinshun , Zhang Lina , Zhang Xiaohong , Xie Yangyang , Dai Xiaoyu , Liao Qi 
Published: March 2019

Abstract

Motivation
Genome-scale CRISPR/Cas9 system has been a democratized gene editing technique and widely used to investigate gene functions in some biological processes and diseases especially cancers. Aiming to characterize gene aberrations and assess their effects on cancer, we designed a pipeline to identify the essential genes for pan-cancer.

Methods
CRISPR screening data were used to identify the essential genes that were collected from published data and integrated by Robust Rank Aggregation algorithm. Then, hypergeometrics test and random walks with restart (RWR) were used to predict additional essential genes on broader scale. Finally, the expression status and potential roles of these genes were explored based on TCGA portal and regulatory network analysis.

Results
We collected 926 samples from 10 CRISPR-based screening studies involving 33 different types of cancer to identify cancer-essential genes, which consists of 799 protein-coding genes (PCGs) and 97 long non-coding RNAs (lncRNAs). Then, we constructed a ‘bi-colored’ network with both PCGs and lncRNAs and applied it to predict additional essential genes including 495 PCGs and 280 lncRNAs on a broader scale using hypergeometrics test and RWR. After obtaining all essential genes, we further investigated their potential roles in cancer and found that essential genes have higher and more stable expression levels, and are associated with multiple cancer-associated biological processes and survival time. The regulatory network analysis detected two intriguing modules of essential genes participating in the regulation of cell cycle and ribosome biogenesis in cancer.

Availability and implementation

Supplementary information
Supplementary data are available at Bioinformatics online.
epic2 efficiently finds diffuse domains in ChIP-seq data
Authors: Stovner Endre Bakken , Sætrom Pål 
Published: March 2019

AbstractSummaryData from chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) generally contain either narrow peaks or broad and diffusely enriched domains. The SICER ChIP-seq caller has proven adept at finding diffuse domains in ChIP-seq data, but it is slow, requires much memory, needs manual installation steps and is hard to use. epic2 is a complete rewrite of SICER that is focused on speed, low memory overhead and ease-of-use.Availability and implementationThe MIT-licensed code is available at https://github.com/biocore-ntnu/epic2.Supplementary informationSupplementary data are available at Bioinformatics online.
Too Close for Comfort: Direct Address and the Affective Pull of the Confessional Comic Woman in Chewing Gum and Fleabag
Authors: Woods Faye 
Published: March 2019

AbstractThe 2010s saw a boom in television comedies, created by, written, and starring women, that explored the bawdy and chaotic lives of protagonists who were experiencing some form of arrested development. These comedies sought to build intimate connections with their imagined audiences by crossing boundaries—social, bodily, and physical—to produce comedies of discomfort. Drawing in part on Rebecca Wanzo’s consideration of “precarious-girl comedy” (2016) I examine how two British television comedies intensified these intimate connections through the use of direct address, binding the audience tightly to the sexual and social misadventures of their twenty-something female protagonists. Michaela Coel’s Chewing Gum (E4, 2015–2017) follows naïve and desperately horny black working-class Londoner Tracey in her quest for sexual experience, and Phoebe-Waller Bridges’ Fleabag (BBC Three, 2016–) documents an unnamed upper-middle-class white woman’s sharply misanthropic journey through grief. In both programmes direct address serves to intensify the embrace of bodily affect and intimate access to interiority found in the “precarious-girl comedy” (Wanzo, 2016), producing moments of comic and emotional repulsion. Each program uses direct address’s blend of directness and distance to different ends, but both draw audiences at times uncomfortably close to the singular perspective of their protagonists, creating an intensely affective comic intimacy.
Eligibility for a Shorter Treatment Regimen for Multidrug-resistant Tuberculosis in the United States, 2011–2016
Authors: Tsang Clarisse A , Shah Neha , Armstrong Lori R , Marks Suzanne M 
Published: March 2019

Abstract

Background
In 2016, the World Health Organization (WHO) recommended a shorter (9–12 month) multidrug-resistant tuberculosis (MDR-TB) treatment regimen (as compared to the conventional 18–24 month regimen) for patients without extrapulmonary TB, pregnancy, a previous second-line TB medication exposure, or drug resistance to pyrazinamide, ethambutol, kanamycin, moxifloxacin, ethionamide, or clofazimine. The recommendation was based on successful clinical trials conducted in Asia and Africa, but studies, using mainly European data, have shown few patients in higher-resource settings would meet WHO eligibility criteria.

Methods
We assessed eligibility for the shorter regimen among US MDR-TB cases that had full drug susceptibility testing (DST) results and were reported during 2011–2016 to the US National TB Surveillance System. We estimated costs by applying the eligibility criteria for the shorter regimen, and proportional inpatient/outpatient costs from a previous, population-based study, to all MDR-TB patients reported to the National TB Surveillance System.

Results
Of 586 reported MDR-TB cases, 10% (59) were eligible for the shorter regimen. Of 527 ineligible patients, 386 had full DST, of which 246 were resistant to ethambutol and 217 were resistant to pyrazinamide. Compared with conventional MDR-TB treatment, implementing the shorter regimen would have reduced the US annual societal MDR-TB cost burden by 4%, but the cost burden for eligible individuals would have been reduced by 37–46%.

Conclusions
Relying on full DST use, our analysis found a minority of US MDR-TB patients would have been eligible for the shorter regimen. Cost reductions would have been minimal for society, but large for eligible individuals.