bluuebunny/crossref_metadata_2025_split huggingface dataset:
MitoFlex: an efficient, high-performance toolkit for animal mitogenome assembly, annotation and visualization
Authors: Li Jun-Yu , Li Wei-Xuan , Wang An-Tai , Zhang Yu 
Published: February 2021

Abstract

Summary
MitoFlex is a linux-based mitochondrial genome analysis toolkit, which provides a complete workflow of raw data filtering, de novo assembly, mitochondrial genome identification and annotation for animal High Throughput Sequencing data. The overall performance was compared between MitoFlex and its analogue MitoZ, in terms of protein-coding gene recovery, memory consumption and processing speed.

Availabilityand implementation
MitoFlex is available at https://github.com/Prunoideae/MitoFlex under GPLv3 license.

Supplementary information
Supplementary data are available at Bioinformatics online.
Fossil pollen from early Palaeogene sediments in western India provides phylogenetic insights into divergence history and pollen character evolution in the pantropical family Ebenaceae
Authors: Bansal Mahi , Nagaraju Shivaprakash K , Mishra Ashish Kumar , Selvaraj Jeyakumar , Patnaik Rajeev , Prasad Vandana 
Published: February 2021

AbstractMany plant families lack substantive fossil records, limiting our understanding of their origin and evolution. The abundance and preservation potential of pollen through geological time have helped to overcome such limitations and have provided reliable fossils for reconstructing biogeographical history and character evolution in many angiosperm families. Here, using scanning electron microscopy, we identified six Ebenaceae-type fossil pollen grains from early Palaeogene sediments of western India. Phenetic and phylogenetic analyses using pollen characters of fossil and extant taxa reavealed affinities of these fossils to three genera of Ebenaceae (Euclea, Royena and Diospyros). Furthermore, our divergence dating analysis using these fossils as priors suggested a Gondwanan origin for the family during the mid-Cretaceous [c. 107 Mya, 95% highest posterior density (HPD): 100–112 Mya] and supports the boreotropical and ‘out of India’ dispersal hypotheses as the most probable explanations for the present global distribution of the family. The study also supports the dispersal of the family into India, from Africa, through the Kohistan–Ladakh Arc during the Palaeocene. Finally, comparative phylogenetic analyses suggest significant synapomorphic and phylogenetic signals for a few selected pollen characters in Ebenaceae. Our findings have important implications for understanding the biogeography and evolution of the highly diverse and ecologically and economically important family Ebenaceae.
Modelling sudden cardiac death risks factors in patients with coronavirus disease of 2019: the hydroxychloroquine and azithromycin case
Authors: Montnach Jérôme , Baró Isabelle , Charpentier Flavien , De Waard Michel , Loussouarn Gildas 
Published: February 2021

Abstract

Aims
Coronavirus disease of 2019 (COVID-19) has rapidly become a worldwide pandemic. Many clinical trials have been initiated to fight the disease. Among those, hydroxychloroquine and azithromycin had initially been suggested to improve clinical outcomes. Despite any demonstrated beneficial effects, they are still in use in some countries but have been reported to prolong the QT interval and induce life-threatening arrhythmia. Since a significant proportion of the world population may be treated with such COVID-19 therapies, evaluation of the arrhythmogenic risk of any candidate drug is needed.

Methods and results
Using the O'Hara-Rudy computer model of human ventricular wedge, we evaluate the arrhythmogenic potential of clinical factors that can further alter repolarization in COVID-19 patients in addition to hydroxychloroquine (HCQ) and azithromycin (AZM) such as tachycardia, hypokalaemia, and subclinical to mild long QT syndrome. Hydroxychloroquine and AZM drugs have little impact on QT duration and do not induce any substrate prone to arrhythmia in COVID-19 patients with normal cardiac repolarization reserve. Nevertheless, in every tested condition in which this reserve is reduced, the model predicts larger electrocardiogram impairments, as with dofetilide. In subclinical conditions, the model suggests that mexiletine limits the deleterious effects of AZM and HCQ.

Conclusion
By studying the HCQ and AZM co-administration case, we show that the easy-to-use O'Hara-Rudy model can be applied to assess the QT-prolongation potential of off-label drugs, beyond HCQ and AZM, in different conditions representative of COVID-19 patients and to evaluate the potential impact of additional drug used to limit the arrhythmogenic risk.
Leveraging Daily Social Experiences to Motivate Healthy Aging
Authors: Charles Susan T , Röcke Christina , Sagha Zadeh Rana , Martin Mike , Boker Steve , Scholz Urte 
Published: February 2021

AbstractModels of healthy aging highlight the motivating influence of social connections. Social experiences constantly shape our thoughts and behaviors throughout daily life, and these daily processes slowly and consistently influence our health and well-being. In this article, we discuss research that has moved from cross-sectional laboratory designs emphasizing individual behaviors to more naturalistic within-person paradigms linking daily social experiences to emotional, cognitive, and physical well-being. We mention research gaps that need to be filled to advance our knowledge of the powerful forces of the social environment for motivating healthy aging. We also offer future directions to move this research forward. We conclude with an outlook on how to leverage these powerful forces in novel intervention approaches that are sensitive to the constantly changing nature of the person and the environment.
Cost-effectiveness of a mobile technology-enabled primary care intervention for cardiovascular disease risk management in rural Indonesia
Authors: Angell Blake , Lung Thomas , Praveen Devarsetty , Maharani Asri , Sujarwoto Sujarwoto , Palagyi Anna , Oceandy Delvac , Tampubolon Gindo , Patel Anushka , Jan Stephen 
Published: February 2021

Abstract
Cardiovascular diseases (CVD) are the leading cause of death in Indonesia, and there are large disparities in access to recommended preventative treatments across the country, particularly in rural areas. Technology-enabled screening and management led by community health workers have been shown to be effective in better managing those at high risk of CVD in a rural Indonesian population; however, the economic impacts of implementing such an intervention are unknown. We conducted a modelled cost-effectiveness analysis of the SMARThealth intervention in rural villages of Malang district, Indonesia from the payer perspective over a 10-year period. A Markov model was designed and populated with epidemiological and cost data collected in a recent quasi-randomized trial, with nine health states representing a differing risk for experiencing a major CVD event. Disability-Adjusted Life Years (DALYs) were estimated for the intervention and usual care using disability weights from the literature for major CVD events. Annual treatment costs for CVD treatment and prevention were $US83 under current care and $US144 for those receiving the intervention. The intervention had an incremental cost-effectiveness ratio of $4288 per DALY averted and $3681 per major CVD event avoided relative to usual care. One-way and probabilistic sensitivity analyses demonstrated that the results were robust to plausible variations in model parameters and that the intervention is highly likely to be considered cost-effective by decision-makers across a range of potentially acceptable willingness to pay levels. Relative to current care, the intervention was a cost-effective means to improve the management of CVD in this rural Indonesian population. Further scale-up of the intervention offers the prospect of significant gains in population health and sustainable progress toward universal health coverage for the Indonesian population.
Workplace health promotion interventions for Australian workers with intellectual disability
Authors: Meacham Hannah , Cavanagh Jillian , Bartram Timothy , Pariona-Cabrera Patricia , Shaw Amie 
Published: February 2021

SummaryWorkplace health promotion (WHP) and the general wellbeing of workers in the Australian workforce should be a priority for all management. Our study argues that management support for workers with an intellectual disability (WWID) can make a difference to their health promotion and ultimately their participation in the workforce. We adopt a qualitative approach, through semi-structured interviews with 22 managers, across various organizations, to examine their perspectives around the WHP of WWID. We integrate the key values of WHP; rights for health, empowerment for health and participation for health (Spencer, Corbin and Miedema, Sustainable development goals for health promotion: a critical frame analysis, Health Promot Int 2019;34:847–58) into the four phases of WHP interventions; needs assessment, planning, implementation and evaluation (Bortz and Döring, Research Methods and Evaluation for Human and Social Scientists, Heidelberg: Springer, 2006) and examine management perspectives (setting-based approach) on WHP of WWID. Where this integration had taken place, we found some evidence of managers adopting more flexible, innovative and creative approaches to supporting the health promotion of WWID. This integration seemed to drive continuous improvement for WWID health promotion at the workplace. We also found evidence that some organizations, such an exemplar film company, even over deliver in terms of supporting WWID needs by encouraging their capabilities in film making interventions, whilst others are more direct in their support by matching skills to routine jobs. Our approach demonstrates that incorporating key WHP values into the four-phase WHP framework is critical for the effective health promotion of WWID.
Political discourse and the Nine Years’ War in late Elizabethan Ireland, c.1593–1603
Authors: Heffernan David 
Published: February 2021

Abstract
In the late Elizabethan period Ireland became a critical focus of the Tudor regime as the Nine Years War (c.1593-1603) threatened English rule in the second Tudor kingdom and the country became a theatre of the Anglo-Spanish War (1585-1604). As a result of this military emergency officials in Ireland began composing a deluge of policy papers from the mid-1590s onwards. Over two hundred of these treatises are extant. This paper provides the first systematic overview of this war-time discourse on Ireland. In doing so it sheds light on these writings and their significance for the history of late Elizabethan Ireland.
Imputed gene expression risk scores: a functionally informed component of polygenic risk
Authors: Pain Oliver , Glanville Kylie P , Hagenaars Saskia , Selzam Saskia , Fürtjes Anna , Coleman Jonathan R I , Rimfeld Kaili , Breen Gerome , Folkersen Lasse , Lewis Cathryn M 
Published: February 2021

AbstractIntegration of functional genomic annotations when estimating polygenic risk scores (PRS) can provide insight into aetiology and improve risk prediction. This study explores the predictive utility of gene expression risk scores (GeRS), calculated using imputed gene expression and transcriptome-wide association study (TWAS) results.The predictive utility of GeRS was evaluated using 12 neuropsychiatric and anthropometric outcomes measured in two target samples: UK Biobank and the Twins Early Development Study. GeRS were calculated based on imputed gene expression levels and TWAS results, using 53 gene expression–genotype panels, termed single nucleotide polymorphism (SNP)-weight sets, capturing expression across a range of tissues. We compare the predictive utility of elastic net models containing GeRS within and across SNP-weight sets, and models containing both GeRS and PRS. We estimate the proportion of SNP-based heritability attributable to cis-regulated gene expression.GeRS significantly predicted a range of outcomes, with elastic net models combining GeRS across SNP-weight sets improving prediction. GeRS were less predictive than PRS, but models combining GeRS and PRS improved prediction for several outcomes, with relative improvements ranging from 0.3% for height (P = 0.023) to 4% for rheumatoid arthritis (P = 5.9 × 10−8). The proportion of SNP-based heritability attributable to cis-regulated expression was modest for most outcomes, even when restricting GeRS to colocalized genes.GeRS represent a component of PRS and could be useful for functional stratification of genetic risk. Only in specific circumstances can GeRS substantially improve prediction over PRS alone. Future research considering functional genomic annotations when estimating genetic risk is warranted.
Maximum sustainable yield in the EU’s Common Fisheries Policy - a political history
Authors: Earle Michael 
Published: February 2021

Abstract
The incorporation of MSY into the EU’s Common Fisheries Policy (CFP) is traced from the original fisheries objectives in the Treaty of Rome of 1957 through its first mention in the CFP basic regulation of 2013 up to the recent Baltic Sea management plan, in which it has become operationalized. Emphasis is placed on the dynamics of the EU’s political processes, the impact of non-fisheries-related institutional power struggles and the consequences of political negotiations that include scientific concepts. Criticisms by Sidney Holt, of both MSY as a management objective and the use of surplus production models, are included.
Unearthing Ambiguities: Post-Genocide Justice in Raoul Peck’s Sometimes in April and the ICTR case Nahimana et al.
Authors: Katila Anna 
Published: February 2021

Abstract
This article examines Raoul Peck’s portrayal of post-genocide justice in Rwanda in his film Sometimes in April (2005). The film, which depicts the 1994 genocide against the Tutsi and its aftermath a decade later, resonates with the ICTR case Prosecutor v. Nahimana et al. with its focus on hate speech as genocide. The shared questions connect the two distinct narrative forms that are part of the global social discourse on Rwanda, allowing them to be analysed side by side. Building upon close readings, this article asks: Who is guilty and what counts as a crime? What kind of impact do justice mechanisms have? Whose interests does the ICTR serve? Extending interdisciplinary research on Rwanda across law and cultural studies, I argue that analysing Sometimes in April helps unearth ambiguities within and surrounding the ICTR. Peck’s film and the legal case together communicate a rounded understanding of post-genocide justice to outside audiences, as it is experienced or perceived from local and international perspectives.
Ambient Prime Geodesic Theorems on Hyperbolic 3-Manifolds
Authors: Dever Lindsay , Milićević Djordje 
Published: February 2021

Abstract
We prove prime geodesic theorems counting primitive closed geodesics on a compact hyperbolic 3-manifold with length and holonomy in prescribed intervals, which are allowed to shrink. Our results imply effective equidistribution of holonomy and have both the rate of shrinking and the strength of the error term fully symmetric in length and holonomy.
EU Roadmap to Cleaner, Greener Data Centres
Authors: Booth John 
Published: February 2021

Abstract
While our exit from the European Union is very much in the news, our shared purpose and collaboration with our neighbours isn't so widely celebrated. John Booth MBCS, Vice Chair of the Green IT SG and Managing Director of Carbon3IT, looks at energy hungry data centres and explains how (and why) the green tide is turning.
An international inventory of antimicrobial stewardship (AMS) training programmes for AMS teams
Authors: Weier Naomi , Nathwani Dilip , Thursky Karin , Tängdén Thomas , Vlahović-Palčevski Vera , Dyar Oliver , Beović Bojana , Levy Hara Gabriel , Patel Rahul , Pulcini Céline , Zaidi Syed Tabish R 
Published: February 2021

AbstractBackgroundHealthcare professionals are increasingly expected to lead antimicrobial stewardship (AMS) initiatives. This role in complex healthcare environments requires specialized training.ObjectivesLittle is known about the types of AMS training programmes available to clinicians seeking to play a lead role in AMS. We aimed to identify clinicians’ awareness of AMS training programmes, characteristics of AMS training programmes available and potential barriers to participation.MethodsAMS training programmes available were identified by members of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) via an online survey and through an online search in 2018. Individual training programme course coordinators were then contacted (September–October 2018) for data on the target audience(s), methods of delivery, intended outcomes and potential barriers to accessing the training programme.ResultsA total of 166/250 ESGAP members (66%) responded to the survey, nominating 48 unique AMS training programmes. An additional 32 training programmes were identified through an online search. AMS training programmes were from around the world. Less than half (44.4%) of respondents were aware of one or more AMS training programmes available, with pharmacists more aware compared with medical doctors and other professionals (73% versus 46% and 25%, respectively). AMS training programmes were most commonly delivered online (59%) and aimed at medical doctors (46%). Training costs and a lack of recognition by health professional societies were the most frequently cited barriers to participation in AMS training programmes.ConclusionsThe development of a systematic inventory of AMS training programmes around the globe identifies opportunities and limitations to current training available. Improving access and increasing awareness amongst target participants will support improved education in AMS.
Keeping Camouflage Out of the Classroom: The Safe Schools Declaration and the Guidelines for Protecting Schools and Universities from Military Use During Armed Conflict
Authors: Zwanenburg Marten 
Published: February 2021

Abstract
This article discusses the ‘Safe Schools Declaration’ and the ‘Guidelines for Protecting Schools and Universities from Military use during Armed Conflict’. The latter are set of non-binding guidelines that aim to improve the protection of schools and universities during armed conflict. The former is a political declaration through which States can endorse the Guidelines. The article looks at the drafting process of the two documents, which involved non-governmental organizations (NGOs), international organizations and States. The article argues that the involvement of NGOs can be seen as reflective of a trend in which NGOs are increasingly involved in normative International Humanitarian Law (IHL) development. The role of international organizations was less pronounced, but nevertheless notable because international organizations traditionally do not have an active role in the field of IHL. The article contains an analysis of the Declaration and Guidelines, against the background of the applicable legal framework to the protection of schools and universities during armed conflict. It concludes that the principal focus of the Guidelines is the prevention of the use of schools and universities by armed forces in support of the military effort. IHL does not contain a rule prohibiting such use, but it can have far-reaching negative consequences for education. Other guidelines relate to, inter alia (limitations to), destroying or attacking schools and universities. These guidelines, while sometimes using phraseology from provisions of IHL treaty law, also largely go beyond existing obligations under IHL.
Cabazitaxel versus abiraterone or enzalutamide in metastatic castration-resistant prostate cancer: post hoc analysis of the CARD study excluding chemohormonal therapy for castrate-naive disease
Authors: Suzuki Hiroyoshi , Castellano Daniel , de Bono Johann , Sternberg Cora N , Fizazi Karim , Tombal Bertrand , Wülfing Christian , Foster Meredith C , Ozatilgan Ayse , Geffriaud-Ricouard Christine , de Wit Ronald 
Published: February 2021

Abstract

Background
In the CARD study (NCT02485691), cabazitaxel significantly improved clinical outcomes versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel and the alternative androgen-signalling-targeted inhibitor. However, some patients received docetaxel or the prior alternative androgen-signalling-targeted inhibitor in the metastatic hormone-sensitive (mHSPC) setting. Therefore, the CARD results cannot be directly translated to a Japanese population.

Methods
Patients (N = 255) received cabazitaxel (25 mg/m2 IV Q3W, prednisone, G-CSF) versus abiraterone (1000 mg PO, prednisone) or enzalutamide (160 mg PO) after prior docetaxel and progression ≤12 months on the alternative androgen-signalling-targeted inhibitor. Patients who received combination therapy for mHSPC were excluded (n = 33) as docetaxel is not approved in this setting in Japan.

Results
A total of 222 patients (median age 70 years) were included in this subanalysis. Median number of cycles was higher for cabazitaxel versus androgen-signalling-targeted inhibitors (7 versus 4). Clinical outcomes favoured cabazitaxel over abiraterone or enzalutamide including, radiographic progression-free survival (rPFS; median 8.2 versus 3.4 months; P &lt; 0.0001), overall survival (OS; 13.9 versus 11.8 months; P = 0.0102), PFS (4.4 versus 2.7 months; P &lt; 0.0001), confirmed prostate-specific antigen response (37.0 versus 14.4%; P = 0.0006) and objective tumour response (38.9 versus 11.4%; P = 0.0036). For cabazitaxel versus androgen-signalling-targeted inhibitor, grade ≥ 3 adverse events occurred in 55% versus 44% of patients, with adverse events leading to death on study in 2.7% versus 5.7%.

Conclusions
Cabazitaxel significantly improved outcomes including rPFS and OS versus abiraterone or enzalutamide and are reflective of the Japanese patient population. Cabazitaxel should be considered the preferred treatment option over abiraterone or enzalutamide in this setting.
miR-424-5p reduces 5-fluorouracil resistance possibly by inhibiting Src/focal adhesion kinase signalling-mediated epithelial–mesenchymal transition in colon cancer cells
Authors: Liu Youqiang , Wang Guiying , Li Yong , Zhao Qun , Fan Liqiao , Tan Bibo , Li Baokun , Yu Bin , Xi Jinchuan 
Published: February 2021

Abstract

Objectives
miR-424-5p negatively regulates various malignant biological behaviours in tumour cells. We explored the relationship between miR-424-5p and 5-fluorouracil resistance in colon cancer cells.

Methods
We developed 5-fluorouracil-resistant HT-29 cells and detected miR-424-5p expression using real-time fluorescence quantitative PCR. Cell viability was assessed using Cell Counting Kit-8 (CCK-8) assay. Immunofluorescence and western blotting were performed to determine protein levels. Apoptosis was detected by Annexin V-FITC/PI staining.

Key findings
miR-424-5p was downregulated in 5-fluorouracil-resistant HT-29 cells. A miR-424-5p mimic enhanced the sensitivity of the resistant cells to 5-fluorouracil, whereas a miR-424-5p inhibitor promoted 5-fluorouracil resistance in HT-29 cells. Furthermore, the miR-424-5p mimic downregulated vimentin and upregulated E-cadherin in 5-fluorouracil-resistant HT-29 cells, whereas the miR-424-5p inhibitor exhibited opposite effects. The miR-424-5p inhibitor significantly inhibited 5-fluorouracil-induced HT-29 cell apoptosis and Src and focal adhesion kinase phosphorylation, whereas the miR-424-5p mimic showed opposite effects. Pretreatment with Src inhibitor 1 or focal adhesion kinase inhibitor 2 blocked the increase in Src and focal adhesion kinase phosphorylation and vimentin expression level and the decrease in E-cadherin expression level in miR-424-5p inhibitor-exposed HT-29 cells.

Conclusions
miR-424-5p suppressed epithelial–mesenchymal transition by inhibiting the Src/focal adhesion kinase signalling pathway to reduce 5-fluorouracil resistance in colon cancer cells.