bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with cisplatin in patients with head and neck cancer: theWISTERIAtrial protocol
Authors: Kong Anthony , Good James , Kirkham Amanda , Savage Joshua , Mant Rhys , Llewellyn Laura , Parish Joanna , Spruce Rachel , Forster Martin , Schipani Stefano , Harrington Kevin , Sacco Joseph , Murray Patrick , Middleton Gary , Yap Christina , Mehanna Hisham 
Published: March 2020

IntroductionPatients with head and neck squamous cell carcinoma with locally advanced disease often require multimodality treatment with surgery, radiotherapy and/or chemotherapy. Adjuvant radiotherapy with concurrent chemotherapy is offered to patients with high-risk pathological features postsurgery. While cure rates are improved, overall survival remains suboptimal and treatment has a significant negative impact on quality of life.Cell cycle checkpoint kinase inhibition is a promising method to selectively potentiate the therapeutic effects of chemoradiation. Our hypothesis is that combining chemoradiation with a WEE1 inhibitor will affect the biological response to DNA damage caused by cisplatin and radiation, thereby enhancing clinical outcomes, without increased toxicity. This trial explores the associated effect of WEE1 kinase inhibitor adavosertib (AZD1775).Methods and analysisThis phase I dose-finding, open-label, multicentre trial aims to determine the highest safe dose of AZD1775 in combination with cisplatin chemotherapy preoperatively (group A) as a window of opportunity trial, and in combination with postoperative cisplatin-based chemoradiation (group B).Modified time-to-event continual reassessment method will determine the recommended dose, recruiting up to 21 patients per group. Primary outcomes are recommended doses with predefined target dose-limiting toxicity probabilities of 25% monitored up to 42 days (group A), and 30% monitored up to 12 weeks (group B). Secondary outcomes are disease-free survival times (groups A and B). Exploratory objectives are evaluation of pharmacodynamic (PD) effects, identification and correlation of potential biomarkers with PD markers of DNA damage, determine rate of resection status and surgical complications for group A; and quality of life in group B.Ethics and disseminationResearch Ethics Committee, Edgbaston, West Midlands (REC reference 16/WM/0501) initial approval received on 18/01/2017. Results will be disseminated via peer-reviewed publication and presentation at international conferences.Trial registration numberISRCTN76291951andNCT03028766.
Long-term patient satisfaction and durability of laparoscopic anti-reflux surgery in a large Danish cohort: study protocol for a retrospective cohort study with development of a novel scoring system for patient selection
Authors: Sanberg Ljungdalh Jonas , Rubin Katrine Hass , Durup Jesper , Houlind Kim Christian 
Published: March 2020

IntroductionLaparoscopic anti-reflux surgery is standard of care in surgical treatment of gastro-oesophageal reflux disease and is not without risks of adverse effects, including disruption of the fundoplication and postfundoplication dysphagia, in some cases leading to reoperation. Non-surgical factors such as pre-existing anxiety or depression influence postoperative satisfaction and symptom relief. Previous studies have focused on a short-term follow-up or only certain aspects of disease, such as reoperation or postoperative quality of life. The aim of this study is to evaluate long-term patient-satisfaction and durability of laparoscopic anti-reflux surgery in a large Danish cohort using a comprehensive multimodal follow-up, and to develop a clinically applicable scoring system usable in selecting patients for anti-reflux surgery.Methods and analysisThe study is a retrospective cohort study utilising data from patient records and follow-up with patient-reported quality of life as well as registry-based data. The study population consists of all adult patients having undergone laparoscopic anti-reflux surgery at The Department of Surgery, Kolding Hospital, a part of Lillebaelt Hospital Denmark in an 11-year period. From electronic records; patient characteristics, preoperative endoscopic findings, reflux disease characteristics and details on type of surgery, will be identified. Disease-specific quality of life and dysphagia will be collected from a patient-reported follow-up. From Danish national registries, data on comorbidity, reoperative surgery, use of pharmacological anti-reflux treatment, mortality and socioeconomic factors will be included. Primary outcome of this study is treatment success at follow-up.Ethics and disseminationStudy approval has been obtained from The Danish Patient Safety Agency, The Danish Health Data Authority and Statistics Denmark, complying to Danish and EU legislation. Inclusion in the study will require informed consent from participating subjects. The results of the study will be published in peer-reviewed medical journals regardless of whether these are positive, negative or inconclusive.Trial registration numberClinicaltrials.gov (NCT03959020).
Structural barriers to condom access in a community-based cohort of sex workers in Vancouver, Canada: influence of policing, violence and end-demand criminalisation
Authors: Goldenberg Shira , Liyanage Ruchi , Braschel Melissa , Shannon Kate 
Published: March 2020

ObjectivesSex workers (SWs) face a disproportionate burden of HIV/sexually transmitted infections (STIs), violence and other human rights violations. While recent HIV prevention research has largely focused on the HIV cascade, condoms remain a cornerstone of HIV prevention, requiring further research attention. Given serious concerns regarding barriers to condom use, including policing, violence and ‘end-demand’ sex work criminalisation, we evaluated structural correlates of difficulty accessing condoms among SWs in Vancouver over an 8-year period.MethodsBaseline and prospective data were drawn from a community-based cohort of women SWs (2010–2018). SWs completed semi-annual questionnaires administered by a team that included lived experience (SWs). Multivariable logistic regression using generalised estimating equations (GEE) modelled correlates of difficulty accessing condoms over time.ResultsAmong 884 participants, 19.1% reported difficulty accessing condoms during the study. In multivariable GEE analysis, exposure to end-demand legislation was not associated with improved condom access; identifying as a sexual/gender minority (adjusted odds ratio (aOR) 1.62, 95% CI 1.16 to 2.27), servicing outdoors (aOR 1.52, 95% CI 1.17 to 1.97), physical/sexual workplace violence (aOR 1.98, 95% CI 1.44 to 2.72), community violence (aOR 1.79, 95% CI 1.27 to 2.52) and police harassment (aOR 1.66, 95% CI 1.24 to 2.24) were associated with enhanced difficulty accessing condoms.ConclusionsOne-fifth of SWs faced challenges accessing condoms, suggesting the need to scale-up SW-tailored HIV/STI prevention. Despite the purported goal of ‘protecting communities’, end-demand criminalisation did not mitigate barriers to condom access, while sexual/gender minorities and those facing workplace violence, harassment or those who worked outdoors experienced poorest condom accessibility. Decriminalisation of sex work is needed to support SWs’ labour rights, including access to HIV/STI prevention supplies.
Surgical or medical abortion of pregnancies between 13+0and 23+6weeks’ gestation? A systematic review and new NICE national guidelines
Authors: Schmidt-Hansen Mia , Lohr Patricia A , Cameron Sharon , Hasler Elise 
Published: March 2020

BackgroundAbortion in the second trimester may be performed surgically or medically. The objective of this systematic review was to examine the effectiveness, safety and acceptability/satisfaction of surgical compared with medical abortion of pregnancy between 13+0and 23+6weeks’ gestation for a new national guideline.MethodsWe searched Embase, Medline and the Cochrane Library on 4 March 2019. We included randomised controlled trials (RCTs; any size) and non-randomised comparative studies with n≥100 in each arm, published in English from 1985. Risk-of-bias was assessed using the Cochrane Collaboration checklist for RCTs. Meta-analysis of risk ratios (RRs)used the Mantel-Haenszel method. The quality of the evidence was assessed using GRADE.ResultsTwo RCTs (n=140) were included. ‘Incomplete abortion requiring surgical intervention’ was clinically significantly higher with medical than surgical methods (RR=4.58, 95% CI 1.07 to 19.64). ‘Abortion completed by the intended method’ was statistically, but not clinically, significantly lower after medical than surgical methods, but was marked by high between-study heterogeneity (RR=0.88, 95% CI 0.79 to 0.98). To the extent that ‘haemorrhage requiring transfusion/≥500 mL blood loss’, ‘uterine injury’, ‘cervical injury requiring repair’ and ‘infection reported within 1 month of abortion’ were reported, they did not differ significantly between methods. Depending on measurement method, ‘patient satisfaction/acceptability’ was either clinically significantly higher or comparable after surgical than medical methods. The quality of this evidence was limited by low event rates and attrition bias.ConclusionBased on this evidence and consensus, women should be offered the choice of medical or surgical methods of abortion between 13+0and 23+6weeks’ gestation, unless not clinically appropriate.
Analytical study of holographic p-wave superfluid models in Gauss–Bonnet gravity
Authors: Lai Chuyu , He Tangmei , Pan Qiyuan , Jing Jiliang 
Published: March 2020

AbstractIn Gauss–Bonnet gravity, we analytically investigate the p-wave superfluid models in five dimensional AdS soliton and AdS black hole in order to explore the influences of the higher curvature correction on the holographic superfluid phase transition. We observe that the analytical findings are in good agreement with the numerical computations. Our results show that the critical chemical potential of the system increases with the increase of the Gauss–Bonnet parameter in AdS soliton background, while the critical temperature decreases as the Gauss–Bonnet factor grows if the phase transition of the system is of the second order in AdS black hole background, both of which indicate that the higher curvature correction hinders the formation of the condensation of the vector operator. Moreover, the critical exponent of the system takes the mean-field value 1/2, which is independent of the Gauss–Bonnet parameter and the spatial component of the gauge field.
Y(4626) as a molecular state from interaction $${D}^*_s{\bar{D}}_{s1}(2536)-{D}_s{\bar{D}}_{s1}(2536)$$
Authors: He Jun , Liu Yi , Zhu Jun-Tao , Chen Dian-Yong 
Published: March 2020

AbstractRecently, a new structure Y(4626) was reported by the Belle Collaboration in the process $$e^+e^-\rightarrow D_s^+D_{s1}(2536)^-$$e+e-→Ds+Ds1(2536)-. In this work, we propose an assignment of the Y(4626) as a $${D}^*_s{\bar{D}}_{s1}(2536)$$Ds∗D¯s1(2536) molecular state, which decays into the $$D_s^+D_{s1}(2536)^-$$Ds+Ds1(2536)- channel through a coupling between $${D}^*_s{\bar{D}}_{s1}(2536)$$Ds∗D¯s1(2536) and $${D}_s{\bar{D}}_{s1}(2536)$$DsD¯s1(2536) channels. With the help of the heavy quark symmetry, the potential of the interaction $${D}^*_s{\bar{D}}_{s1}(2536)-{D}_s{\bar{D}}_{s1}(2536)$$Ds∗D¯s1(2536)-DsD¯s1(2536) is constructed within the one-boson-exchange model, and inserted into the quasipotential Bethe–Salpeter equation. The pole of obtained scattering amplitude is searched for in the complex-energy plane, which corresponds to a molecular state from the interaction $${D}^*_s{\bar{D}}_{s1}(2536)-{D}_s{\bar{D}}_{s1}(2536)$$Ds∗D¯s1(2536)-DsD¯s1(2536). The results suggest that a pole is produced near the $${D}^*_s{\bar{D}}_{s1}(2536)$$Ds∗D¯s1(2536) threshold, which exhibits as a peak in the invariant mass spectrum of the $${D}_s{\bar{D}}_{s1}(2536)$$DsD¯s1(2536) channel at about 4626 MeV. It obviously favors the Y(4626) as a $${D}^*_s{\bar{D}}_{s1}(2536)$$Ds∗D¯s1(2536) molecular state. In the same model, other molecular states from the interaction $${D}^*_s{\bar{D}}_{s1}(2536)-{D}_s{\bar{D}}_{s1}(2536)$$Ds∗D¯s1(2536)-DsD¯s1(2536) are also predicted, which can be checked in future experiments.
ARIMA Supplemented Security Metrics for Quality Assurance and Situational Awareness
Authors: Kohlrausch Jan , Brin Eugene A. 
Published: March 2020

Quality assurance and situational awareness are important areas of interest for CSIRTs and security teams. Significant efforts have been made on defining metrics measuring critical parameters for these fields of application. However, methodical approaches are missing or lacking precision to enable a reliable usage of such metrics for quality assurance and situational awareness.
In this contribution, we introduce a method that generalizes the application of ARIMA time series analysis on a well-defined set of metrics (ARIMA supplemented metrics) to facilitate and support quality assurance and situational awareness services. This method is based on research on ARIMA models and metrics and builds on CSIRT best practices. We show how data analysts and security practitioners can incorporate this method into existing best practices for CSIRT services pertaining to quality assurance and situational awareness.
The applicability of this method is demonstrated by integrating ARIMA supplemented metrics into exemplary processes for quality assurance and situational awareness to support data analysts and security practitioners in CSIRTs and security teams.
Evaluation of Eribulin Combined with Irinotecan for Treatment of Pediatric Cancer Xenografts
Authors: Robles Andrew J. , Kurmasheva Raushan T. , Bandyopadhyay Abhik , Phelps Doris A. , Erickson Stephen W. , Lai Zhao , Kurmashev Dias , Chen Yidong , Smith Malcom A. , Houghton Peter J. 
Published: March 2020

Abstract

Purpose:
Vincristine combined with camptothecin derivatives showed synergy in preclinical pediatric cancer models, and the combinations are effective in treatment of childhood solid tumors. We determined whether the synergy between vincristine and irinotecan extends to eribulin, another microtubule inhibitor.

Experimental Design:
Vincristine or eribulin, alone or combined with irinotecan, was studied in 12 xenograft models. Tumor regression and time to event were used to assess antitumor activity. Pharmacodynamic studies and RNA sequencing (RNA-seq) were conducted 24 and 144 hours after single-agent or combination treatment. Effects on vascular development were studied in Matrigel plugs implanted in mice. The interaction between binary combinations was examined in vitro.

Results:
Eribulin combined with irinotecan was more effective than vincristine–irinotecan in 6 of 12 models. Pharmacodynamic markers induced by eribulin (phospho-histone H3) and irinotecan (γ-H2A.X) were abrogated in combination-treated tumors. The predominant RNA-seq signature in combination-treated tumors was activation of the TP53 pathway with increased nuclear TP53. Massive apoptosis was observed 24 hours only after treatment with the eribulin combination. In vitro, neither combination showed interaction using combination index analysis. Eribulin alone and the combination caused alterations in developing vasculature.

Conclusions:
The eribulin combination is very active in these xenograft models, but not synergistic in vitro. The combination reduced pharmacodynamic markers indicative of single-agent mechanisms but in tumors, dramatically activated the TP53 pathway. Although a mechanism for in vivo synergy requires further study, it is possible that eribulin-induced inhibition of microtubule dynamics enhances irinotecan-induced nuclear accumulation of TP53, leading to rapid cell death.
A new Brachypsectra LeConte from Australia (Coleoptera: Brachypsectridae) with comparative notes on adults and larvae
Authors: Lawrence John F. , Monteith Geoffrey B. , Reid Chris A.M. 
Published: March 2020

A new species, Brachypsectra cleidecostae Lawrence, Monteith & Reid sp. nov., is described from Australia on the basis of one reared adult female from inland Queensland and larvae from the type locality and two other widely separated semi-arid localities in South Australia and Western Australia. Two of the four larval collections were from under tree bark and one was from ground litter. The species is differentiated on both adult and larval characters. The broader mandible with retention of a retinacular tooth may indicate a sister relationship with species of the genus from other continents.
Descriptions of larval and pupal morphologies of Macrohyliota militaris (Erichson) (Silvanidae: Brontinae: Brontini)
Authors: Liu Zhenhua , Ślipiński Adam , Pang Hong 
Published: March 2020

The mature larva and pupa of the Australian silvanid species, Macrohyliota militaris (Erichson) are described from laboratory reared material. This is the first description of immature stages of Silvanidae from Australia. The larva of M. militaris conforms to the general body shape and apparent morphological features of known Brontini and is very similar to the Asian M. sculptus Yoshida & Hirowatari. Larval and pupal features of M. militaris are compared with other known larvae and pupae of Brontini described in the literature.
Contribution to the knowledge of Podischnus Burmeister, 1847 (Coleoptera, Melolonthidae: Dynastinae) with the description of two new species from Brazilian Amazon Forest
Authors: Duarte Paulo Roberto Marinho , Grossi Paschoal Coelho 
Published: March 2020

Two new Podischnus Burmeister, 1847 species are described here: Podischnus limeirai sp. nov. from Gurupi region, Maranhão state, Brazil, the easternmost distribution of the genus; and Podischnus cleidecostae sp. nov. from the Acre state, Western of Brazilian Amazon Forest. New diagnostic characters are illustrated and discussed for the genus. An illustrated identification key for all Podischnus species, and an up-to-date distribution map for the Brazilian species of Podischnus are provided. Moreover, we propose the inclusion of P. limeirai sp. nov. in the Red List of Threatened Species (IUCN) due to the fast loss of the Oriental Amazon Forest remnant fragment in that region.
Long-Term Risk Factors for Dilatation of the Proximal Aorta in a Large Cohort of Children With Bicuspid Aortic Valve
Authors: Blais Samuel , Meloche-Dumas Léamarie , Fournier Anne , Dallaire Frederic , Dahdah Nagib 
Published: March 2020

Background:
Patients with bicuspid aortic valve (BAV) have a higher risk of developing aortic valve dysfunction and progressive proximal aorta dilatation, which can lead to aortic dissection. To this day, identification of children at risk of developing severe aortic dilatation during their pediatric follow-up is still challenging because most studies were restricted to adult subjects. The overarching goal of this study was to identify risk factors of aortic dilatation in children with BAV.

Methods:

We extracted clinical and echocardiographic data of all BAV subjects aged 0 to 20 years followed at Centre Hospitalier Universitaire Sainte-Justine between 1999 and 2016. We excluded subjects with concomitant heart defects and conditions affecting proximal aorta dimensions. Proximal aorta diameters (expressed as
Z
scores) were modeled in relation to age and potential predictive variables in a linear mixed model. The primary outcome was the rate of dilatation.

Results:

We included 761 subjects (3134 echocardiograms) in final analyses. The mean ascending aorta
Z
score progression rate for BAV patient with a normally functioning aortic valve was estimated at 0.05
Z
score unit per year. The strongest predictors of an increased dilatation rate were severe aortic stenosis, moderate and severe aortic regurgitation, and uncorrected coarctation of the aorta. Aortic valve leaflet fusion pattern and sex were not associated with progression rate.

Conclusions:
Children with a normally functioning BAV exhibited a very slow proximal aorta dilatation rate. Ascending aorta dilatation rate was significantly increased in patients with more than mild aortic valve dysfunction but was independent from BAV leaflet fusion type.
Each 0.5°C of Warming Increases Annual Flood Losses in China by More than US$60 Billion
Authors: Jiang Tong , Su Buda , Huang Jinlong , Zhai Jianqing , Xia Jun , Tao Hui , Wang Yanjun , Sun Hemin , Luo Yong , Zhang Liping , Wang Guojie , Zhan Chesheng , Xiong Ming , Kundzewicz Zbigniew W. 
Published: March 2020

AbstractIn the warming climate, flood risk is likely to increase over much of the globe. We present projections of changes of flood losses in China for a range of global warming scenarios, from 1.5° to 4.0°C above the preindustrial temperature, with a 0.5°C step. Projections of flood losses in China are based on river runoff simulations by a distributed hydrological model driven by multiple downscaled general circulation models, the national GDP projected at shared socioeconomic pathways, and the “intensity–loss rate” function. When interpreting changes caused by the combined effect of economic and climatic conditions, flood losses in China are projected to soar in the future, particularly in lowland regions subject to rapid economic growth. Under global warming of 1.5° and 4.0°C, in an average year, flood losses are projected to be, respectively, 4 and 17 times that at present. Pursuing the international climate policy target of limiting global warming is projected to reduce exposure to floods in China. In this way, flood losses in China can be reduced by tens of billions of U.S. dollars (on average, US$67 billion and up to 0.04% of GDP) for each 0.5°C that warming is reduced. Our study improves understanding of the impact of climatic and nonclimatic changes on flood risk. Our scientific contribution is the first study to quantify flood impacts across China under different development pathways (shared socioeconomic pathways) for a broad range of global warming levels.
Interdecadal Variation of Winter Cold Surge Path in East Asia and Its Relationship with Arctic Sea Ice
Authors: Yang Xiaoye , Zeng Gang , Zhang Guwei , Li Zhongxian 
Published: March 2020

AbstractThe paths of winter cold surge (CS) events in East Asia (EA) from 1979 to 2017 are tracked by the Flexible Particle (FLEXPART) model using ERA-Interim daily datasets, and the probability density distribution of the paths is calculated by the kernel density estimation (KDE) method. The results showed that the paths of CSs are significantly correlated with the intensity of the CSs, which shows an interdecadal transition from weak to strong around 1995. CS paths can be classified into two types, namely, the western path type and the northern path type, which were more likely to occur before and after 1995, respectively. Before 1995, the cold air mainly originated from Europe and moved from west to east, and the synoptic features were associated with the zonal wave train. After 1995, cold air accumulated over western Siberia and then invaded EA along the northern path, and the synoptic features were mainly associated with the blocking structure. The geopotential height (GPH) anomalies over the Arctic were abnormally strong. This paper further analyzes the relationship between CSs and winter sea ice concentration (SIC) in the Arctic. The results show that the intensity of CSs is negatively correlated with the Barents SIC (BSIC). When the BSIC declines, the upward wave flux over the Barents Sea is enhanced and expanded to the midlatitude region. GPH anomalies over the Arctic are positive and form a negative AO-like pattern, which is conducive to the formation of the northern path CS. Furthermore, the observed results are supported by numerical experiments with the NCAR Community Atmosphere Model, version 5.3 (CAM5.3).