bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-based screen for discovering lipopolysaccharide biogenesis inhibitors
Authors: Zhang Ge , Baidin Vadim , Pahil Karanbir S. , Moison Eileen , Tomasek David , Ramadoss Nitya S. , Chatterjee Arnab K. , McNamara Case W. , Young Travis S. , Schultz Peter G. , Meredith Timothy C. , Kahne Daniel 
Published: June 2018

Significance
The outer membrane of gram-negative bacteria contains LPS on the cell surface. The presence of LPS creates an effective permeability barrier that protects gram-negative bacteria from small hydrophobic molecules. Because the entire LPS biogenesis pathway, including biosynthesis and transport, is highly conserved, proteins involved are attractive targets for antibiotic discovery. Historically, it has been challenging to target LPS biogenesis since many of the components are membrane proteins with hard-to-assay activities. Utilizing the nonessentiality of this pathway in a gram-negative pathogen, we developed a cell-based screen specific to LPS biogenesis. We identified a small-molecule inhibitor targeting an essential component of the pathway, MsbA, and validated it as an antibacterial target using a combination of genetics, biochemistry, and cellular assays.
Structural basis for recognition of human 7SK long noncoding RNA by the La-related protein Larp7
Authors: Eichhorn Catherine D. , Yang Yuan , Repeta Lucas , Feigon Juli 
Published: June 2018

Significance
The 7SK ribonucleoprotein (RNP) complex regulates the activity of the kinase positive transcription elongation factor b (P-TEFb), an essential activator of RNA Polymerase II transcription. The human La-related protein group 7 (hLarp7) protein is an essential and constitutively assembled component of the 7SK RNP and is required for 7SK RNA stability and P-TEFb recruitment. We report the structure of the hLarp7 C-terminal RNA recognition motif bound to the 7SK stem-loop 4, revealing a unique binding interface. From this and other available structures, we generate a structural model of hLarp7 bound to the 7SK 3′ end. This work provides seminal insights into the unique recognition of 7SK RNA by hLarp7 and a working model for how hLarp7 assembles with 7SK to form the 7SK RNP.
Dynamically reinforced heterogeneous grain structure prolongs ductility in a medium-entropy alloy with gigapascal yield strength
Authors: Yang Muxin , Yan Dingshun , Yuan Fuping , Jiang Ping , Ma Evan , Wu Xiaolei 
Published: June 2018

Significance
Back stress hardening is usually not obvious in single-phase homogeneous grains, but can be made unusually large and sustained to large tensile strains by creating an unusually heterogeneous grain structure in single-phase alloys with low stacking fault energy (SFE), as demonstrated here for the face-centered cubic CrCoNi medium-entropy alloy. The low SFE facilitates the generation of twinned nanograins and stacking faults during tensile straining, dynamically reinforcing the heterogeneity. Large uniform tensile strain can be achieved after yielding even at gigapascal stress, in the absence of heterogeneities from any second phase.
A brief history of bioinformatics
Authors: Gauthier Jeff , Vincent Antony T , Charette Steve J , Derome Nicolas 
Published: June 2018

AbstractIt is easy for today’s students and researchers to believe that modern bioinformatics emerged recently to assist next-generation sequencing data analysis. However, the very beginnings of bioinformatics occurred more than 50 years ago, when desktop computers were still a hypothesis and DNA could not yet be sequenced. The foundations of bioinformatics were laid in the early 1960s with the application of computational methods to protein sequence analysis (notably, de novo sequence assembly, biological sequence databases and substitution models). Later on, DNA analysis also emerged due to parallel advances in (i) molecular biology methods, which allowed easier manipulation of DNA, as well as its sequencing, and (ii) computer science, which saw the rise of increasingly miniaturized and more powerful computers, as well as novel software better suited to handle bioinformatics tasks. In the 1990s through the 2000s, major improvements in sequencing technology, along with reduced costs, gave rise to an exponential increase of data. The arrival of ‘Big Data’ has laid out new challenges in terms of data mining and management, calling for more expertise from computer science into the field. Coupled with an ever-increasing amount of bioinformatics tools, biological Big Data had (and continues to have) profound implications on the predictive power and reproducibility of bioinformatics results. To overcome this issue, universities are now fully integrating this discipline into the curriculum of biology students. Recent subdisciplines such as synthetic biology, systems biology and whole-cell modeling have emerged from the ever-increasing complementarity between computer science and biology.
Sequencing era methods for identifying signatures of selection in the genome
Authors: Horscroft Clare , Ennis Sarah , Pengelly Reuben J , Sluckin Timothy J , Collins Andrew 
Published: June 2018

AbstractInsights into genetic loci which are under selection and their functional roles contribute to increased understanding of the patterns of phenotypic variation we observe today. The availability of whole-genome sequence data, for humans and other species, provides opportunities to investigate adaptation and evolution at unprecedented resolution. Many analytical methods have been developed to interrogate these large data sets and characterize signatures of selection in the genome. We review here recently developed methods and consider the impact of increased computing power and data availability on the detection of selection signatures. Consideration of demography, recombination and other confounding factors is important, and use of a range of methods in combination is a powerful route to resolving different forms of selection in genome sequence data. Overall, a substantial improvement in methods for application to whole-genome sequencing is evident, although further work is required to develop robust and computationally efficient approaches which may increase reproducibility across studies.
Essential Physiological Differences Characterize Short- and Long-Lived Strains of Drosophila melanogaster
Authors: Gubina Nina , Naudi Alba , Stefanatos Rhoda , Jove Mariona , Scialo Filippo , Fernandez-Ayala Daniel J , Rantapero Tommi , Yurkevych Ihor , Portero-Otin Manuel , Nykter Matti , Lushchak Oleh , Navas Placido , Pamplona Reinald , Sanz Alberto 
Published: June 2018

Abstract
Aging is a multifactorial process which affects all animals. Aging as a result of damage accumulation is the most accepted explanation but the proximal causes remain to be elucidated. There is also evidence indicating that aging has an important genetic component. Animal species age at different rates and specific signaling pathways, such as insulin/insulin-like growth factor, can regulate life span of individuals within a species by reprogramming cells in response to environmental changes. Here, we use an unbiased approach to identify novel factors that regulate life span in Drosophila melanogaster. We compare the transcriptome and metabolome of two wild-type strains used widely in aging research: short-lived Dahomey and long-lived Oregon R flies. We found that Dahomey flies carry several traits associated with short-lived individuals and species such as increased lipoxidative stress, decreased mitochondrial gene expression, and increased Target of Rapamycin signaling. Dahomey flies also have upregulated octopamine signaling known to stimulate foraging behavior. Accordingly, we present evidence that increased foraging behavior, under laboratory conditions where nutrients are in excess increases damage generation and accelerates aging. In summary, we have identified several new pathways, which influence longevity highlighting the contribution and importance of the genetic component of aging.
An experiential learning theory of high level wellness: Australian salutogenic research
Authors: Allen Connie , Boddy Jennifer , Kendall Elizabeth 
Published: June 2018

Summary
At the broadest level, salutogenesis refers to an emphasis on the origins of health, as opposed to a predilection with the determinants of disease. Kickbusch urges health promotion professionals to adopt a salutogenic orientation; directing research and practice towards the question of ‘what creates health?’ This salutogenic study focused on the most pleasant part of the health continuum by asking: (i) what is high level wellness and (ii) how do people attain and maintain this way of being? Semi-structured interviews were conducted with 25 Australian adults who reported a ‘high’ or ‘very high’ level of wellness, health and happiness. Participants described what high level wellness meant to them, their wellness journeys, and the things that helped and hindered their wellbeing. This information was coded, compared and crafted into a constructivist grounded theory. Our interpretation of the data suggests that high level wellness is the sense of peace (wellbeing) that comes from knowing, liking and being one’s best self. Happy, healthy people seem to attain and maintain this way of being over time, through a series of self-initiated experiential learning cycles. The ‘experiential learning theory of high level wellness’ links and extends literature on salutogenesis, eudaimonic wellbeing, self-actualization and experiential learning; positioning everyday people as the leaders of their own life-long wellness journeys. It also suggests a new dimension for Antonovsky’s salutogenic theory: aspiring, not just adapting. Future research could explore the utility of our approach with a range of populations and professions, progressing towards ‘high level wellness for all’.
A GIS-based framework for addressing conflicting objectives in the context of an ecosystem approach to fisheries management—a case study of the Portuguese sardine fishery
Authors: Szalaj D , Wise L , Rodríguez-Climent S , Angélico M M , Marques V , Chaves C , Silva A , Cabral H 
Published: June 2018

Abstract
An ecosystem approach to fisheries management (EAFM) is as a new paradigm in fisheries management. In this study, a combination of geographic information systems (GISs) and multi-criteria decision-making method (MCDM) is proposed as a framework supporting an ecosystem approach to European sardine (Sardina pilchardus, Clupeidae) fishery management in Portugal. This case study was chosen due to the recent severe decline shown by the species. To develop an EAFM for the sardine fishery, a set of criteria were defined based on literature review and expert knowledge. To address multiple conflicting objectives, namely conservation and fisheries, five scenarios were considered: (i) baseline; (ii) nurseries protection; (iii) spawning areas protection; (iv) fishery profit driven, and (v) safeguarding dependent fishing communities. Combination of GIS and MCDM methods highlighted important areas to implement spatial conservation measures for sardine. The analyses indicate that some areas are suitable for conservation in several scenarios, such as the area near Aveiro and the area near the Tejo estuary. However, conservation measures implemented in the area near Aveiro would imply higher economic trade-offs when compared with the actions applied in the region near the Tejo estuary. Results also suggested some of the conservation objectives, such as the protection of sardine eggs and juveniles, to not be compatible. The proposed framework is an important tool supporting EAFM by addressing conflicting objectives, trade-offs and identifying areas that could be considered as potential fishery closure sites or subjected to further analyses.
Implementation of electronic charting is not associated with significant change in physician productivity in an academic emergency department
Authors: Sarangarm Dusadee , Lamb Gregory , Weiss Steven , Ernst Amy , Hewitt Lorraine 
Published: June 2018

Abstract

Objectives
To compare physician productivity and billing before and after implementation of electronic charting in an academic emergency department (ED).

Materials and methods
This retrospective, blinded, observational study compared the 6 months pre-implementation (January to June 2012) with the 6 months post-implementation 1 year later (January to June 2013). Thirty-one ED physicians were recruited, with each physician acting as his/her own control in a before-after design. Productivity was measured via total number of encounters and “productivity index” defined as worked relative value units divided by the clinical full-time equivalent. Values for charges, encounters, and productivity index were determined during each study period and separately for procedures, observational stays, and critical care.

Results
No differences were found for total productivity index per month (758 [623-876] pre-group vs. 756 [673-886] post-group; P = 0.30). There was, however, a 9% decrease in total encounters per month (138 [101-163] pre-group vs. 125 [99-159] post-group; P = 0.01). Significant decreases were seen across all observation stay categories. Conversely, significant increases were seen across all critical care categories. There was no difference in total charges per month.

Discussion
This is one of few studies to demonstrate minimal disruption in physician productivity after transitioning to electronic documentation. The reasons for these findings are likely multi-factorial.

Conclusion
In this study, implementation of electronic charting was not associated with decreases in productivity or billing for total ED care, but may be associated with increases for critical care and decreases for observational stays.
Participatory Visual Research with Displaced Persons: ‘Listening’ to Post-conflict Experiences through the Visual
Authors: Weber Sanne 
Published: June 2018

AbstractResearch with refugees, internally displaced persons (IDPs) and other marginalized groups entails complexities that make it imperative to think through the ethical and methodological strategies to not only ‘do no harm’, but also allow the research to be valuable for the participants. This article contributes to this methodological debate by demonstrating how participatory visual research offers an innovative tool for democratizing research and avoiding the risk of retraumatization. This type of research moreover enables participants to visually represent and communicate their—gender-specific—truth, thus enabling them to counter official representations of their situation and gendered stereotypes of vulnerable IDP women. Participatory visual research can thus become an instrument to contribute to social change, in line with the goals of feminist research. This article describes its use during a research process with women in two communities of returned IDPs in Colombia’s Caribbean coast.
Low-Dose Prasugrel vs Clopidogrel-Based Tailored Premedication for Endovascular Treatment of Cerebral Aneurysms
Authors: Cho Won-Sang , Lee Joongyub , Ha Eun Jin , Kim Kyung Hyun , Lee Jeongjun , Cho Young Dae , Kim Jeong Eun , Han Moon Hee , Kang Hyun-Seung 
Published: June 2018

Abstract

BACKGROUND
Antiplatelet premedication is widely accepted for interventional treatment of cerebral aneurysms to prevent thromboembolism. However, antiplatelet resistance sometimes limits the effectiveness of premedication.

OBJECTIVE
To compare 2 groups administered low-dose prasugrel (PSG group) or clopidogrel-based tailored antiplatelet (CPG group) in terms of platelet function and procedure-related complications.

METHODS
A total of 411 patients with 505 unruptured aneurysms who underwent endovascular treatment within the past 17 mo were retrospectively enrolled in this study. The PSG (225 patients with 277 aneurysms) and CPG groups (186 patients with 228 aneurysms) were administered the respective medication prior to endovascular treatment. We measure the response to the antiplatelet medication with a laboratory test. Episodes of periprocedural bleeding and thromboembolism were compared between the 2 groups.

RESULTS
There were significant differences between the 2 groups in terms of the mean P2Y12 reaction unit values (125.7 in the PSG group vs 251.0 in the CPG group; P < .001) and percentage inhibition (57.8% vs 18.7%, respectively; P < .001). Drug resistance was 29.6% per patient in the CPG group and 2.7% per patient in the PSG group. The PSG group reported 1 thromboembolism and bleeding each; meanwhile, the CPG group reported 7 thromboembolism and 3 bleeding. Compared to clopidogrel administration, prasugrel administration significantly decreased the risk of thromboembolism (weighted hazard ratio, 0.17; 95% confidence interval, 0.03-0.99). However, the risk of bleeding was not significant.

CONCLUSION
Prasugrel was found to be more effective in reducing periprocedural thromboembolism compared to clopidogrel.
Impact of Direct-Acting Antivirals on the Burden of HCV Infection Among Persons Who Inject Drugs and Men Who Have Sex With Men in the Swiss HIV Cohort Study
Authors: Salazar-Vizcaya Luisa , Wandeler Gilles , Fehr Jan , Braun Dominique , Cavassini Matthias , Stoeckle Marcel , Bernasconi Enos , Hoffmann Matthias , Rougemont Mathieu , Béguelin Charles , Rauch Andri ,   the Swiss HIV Cohort Study, Aubert V , Battegay M , Bernasconi E , Böni J , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H F , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Kahlert C , Kaiser L , Keiser O , Klimkait T , Kouyos R D , Kovari H , Ledergerber B , Martinetti G , Martinez de Tejada B , Marzolini C , Metzner K J , Müller N , Nicca D , Pantaleo G , Paioni P , Rauch A , Rudin C , Scherrer A U , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Vernazza P , Wandeler G , Weber R , Yerly S 
Published: June 2018

Abstract
In the Swiss HIV Cohort Study, the number of people who inject drugs with replicating hepatitis C virus (HCV) infection decreased substantially after the introduction of direct-acting antivirals (DAAs). Among men who have sex with men, the increase in DAA uptake and efficacy was counterbalanced by frequent incident HCV infections.
A novel immunodeficient rat model supports human lung cancer xenografts
Authors: He Di , Zhang Junhui , Wu Wanwan , Yi Ning , He Wen , Lu Ping , Li Bin , Yang Nan , Wang Di , Xue Zhigang , Zhang Peng , Fan Guoping , Zhu Xianmin 
Published: June 2018

ABSTRACTPatient‐derived xenograft (PDX) animal models allow the exogenous growth of human tumors, offering an irreplaceable preclinical tool for oncology research. Mice are the most commonly used host for human PDX models, however their small body size limits the xenograft growth, sample collection, and drug evaluation. Therefore, we sought to develop a novel rat model that could overcome many of these limitations. We knocked out Rag1, Rag2, and Il2rg in Sprague Dawley (SD) rats by clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR‐associated protein 9 technology. The development of lymphoid organs is significantly impaired in Rag1−1− Rag2−/− Il2rg−/Υ (designated as SD‐RG) rats. Consequently, SD‐RG rats are severely immunodeficient with an absence of mature T, B, and NK cells in the immune system. After subcutaneous injection of tumor cell lines of different origin, such as NCI‐H460, U‐87MG, and MDA‐MB‐231, the tumors grow significantly faster and larger in SD‐RG rats than in nonobese diabetic–Cg‐Prkdcscid Il2rgtm1Wjl / SzJ mice. Most important of all, we successfully established a PDX model of lung squamous cell carcinoma in which the grafts recapitulate the histopathologic features of the primary tumor for several passages. In conclusion, the severely immunodeficient SD‐RG rats support fast growth of PDX compared with mice, thus holding great potential to serve as a new model for oncology research.—He, D., Zhang, J., Wu, W., Yi, N., He, W., Lu, P., Li, B., Yang, N., Wang, D., Xue, Z., Zhang, P., Fan, G., Zhu, X. A novel immunodeficient rat model supports human lung cancer xenografts. FASEB J. 33, 140–150 (2019). www.fasebj.org
Treatment of Kratom Dependence With Buprenorphine-Naloxone Maintenance
Authors: Buresh Megan 
Published: June 2018

Introduction:
Use of the unregulated herbal supplement kratom is on the rise in the United States. We present a case series of 2 patients who developed kratom dependence and withdrawal who were successfully transitioned to buprenorphine-naloxone maintenance.

Case Summary:
Two patients using kratom to self-treat chronic pain after prescription opioids were discontinued presenting to our clinic with evidence of kratom dependence and withdrawal. On examination, both patients showed signs of mild opioid withdrawal. Both patients were successfully transitioned to buprenorphine-naloxone maintenance via home initiation with control of both their opioid withdrawal and chronic pain.

Conclusions:
Kratom use is on the rise and with increasing evidence of developing opioid-type dependence due to chronic kratom use. This case series shows that buprenorphine can be used to treat kratom dependence and underlying chronic pain that drives it use.
Effectiveness of Kinesio Taping in Patients With Chronic Nonspecific Low Back Pain
Authors: Luz Júnior Maurício Antônio Da , Almeida Matheus Oliveira De , Santos Raiany Silva , Civile Vinicius Tassoni , Costa Leonardo Oliveira Pena 
Published: June 2018

Study Design.
Systematic review.

Objective.
To investigate the effects of Kinesio Taping (KT) in patients with nonspecific low back pain.

Summary of Background Data.
KT is widely used in patients with low back pain.

Methods.
We conducted searches on PubMed, EMBASE, PEDro, SciELO, and LILACS up to February 26, 2018. We included only randomized controlled trials (RCTs) in adults with chronic nonspecific low back pain that compared KT to no intervention or placebo as well as RCTs that compared KT combined with exercise against exercise alone. The methodological quality and statistical reporting of the eligible trials were measured by the 11-item PEDro scale. The quality of the evidence was assessed using the GRADE classification. We considered pain intensity and disability as the primary outcomes. Whenever possible, the data were pooled through meta-analysis.

Results.
We identified 11 RCTs for this systematic review (pooled n = 743). Two clinical trials (pooled n = 100) compared KT to no intervention at the short-term follow-up. Four studies compared KT to placebo (pooled n = 287) at short-term follow-up and two trials (pooled n = 100) compared KT to placebo at intermediate-term follow-up. Five trials (pooled n = 296) compared KT combined with exercises or electrotherapy to exercises or spinal manipulation alone. No statistically significant difference was found for most comparisons.

Conclusion.
Very low to moderate quality evidence shows that KT was no better than any other intervention for most the outcomes assessed in patients with chronic nonspecific low back pain. We found no evidence to support the use of KT in clinical practice for patients with chronic nonspecific low back pain.

Level of Evidence: 1