bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the interplay between robustness and dynamic planning for adaptive radiation therapy*
Authors: Böck Michelle , Eriksson Kjell , Forsgren Anders 
Published: April 2019

Abstract
Interfractional geometric uncertainties can lead to deviations of the actual delivered dose from the prescribed dose distribution. To better handle these uncertainties during the course of treatment, the authors propose a framework for robust adaptive radiation therapy in which a variety of robust adaptive treatment strategies are introduced and evaluated. This variety is a result of optimization variables with various degrees of freedom within robust optimization models that vary in their grade of conservativeness. The different degrees of freedom in the optimization variables are expressed through either time-and-uncertainty-scenario-independence, time-dependence or time-and-uncertainty-scenario-dependence, while the robust models are either based on expected-value-, worst-case- or conditional value-at-risk-optimization. The goal of this study is to understand which mathematical properties of the proposed robust adaptive strategies are relevant such that the accumulated dose can be steered as close as possible to the prescribed dose as the treatment progresses. We apply a result from convex analysis to show that the robust non-adaptive approach under conditions of convexity and permutation-invariance is at least as good as the time-dependent robust adaptive approach, which implies that the time-dependent problem can be solved by dynamically solving the corresponding time-independent problem. According to the computational study, non-adaptive robust strategies may provide sufficient target coverage comparable to robust adaptive strategies if the occurring uncertainties follow the same distribution as those included in the robust model. Moreover, the results indicate that time-and-uncertainty-scenario-dependent optimization variables are most compatible with worst-case-optimization, while time-and-uncertainty-scenario-independent variables find their best match with expected value optimization. In conclusion, the authors introduced a novel framework for robust adaptive radiation therapy and identified mathematical requirements to further develop robust adaptive strategies in order to improve treatment outcome in the presence of interfractional uncertainties.
The costs of competition: injury patterns in 2 Asian colobine monkeys
Authors: Feder Jacob A , Lu Amy , Koenig Andreas , Borries Carola 
Published: April 2019

AbstractAggression rarely escalates to physical conflict because doing so puts individuals at risk of injury. Escalation only pays off when the potential benefits outweigh the potential costs, that is, when resources critical to fitness are at stake. Here, we investigated the occurrence of injury in 2 Asian colobine species: Nepal gray langurs (Semnopithecus schistaceus) and Phayre’s leaf monkeys (Trachypithecus phayrei crepusculus). In both species, younger individuals are higher-ranking and might have greater incentive to fight. However, Nepal gray langurs have a strict breeding season, which may magnify male mating competition, and Phayre’s leaf monkeys, unlike Nepal gray langurs, have female-biased dispersal, which may increase female injury risk during subadulthood. Using long-term data on observed injuries (Nepal gray langurs: n = 208; Phayre’s leaf monkeys: n = 225), we modeled the monthly occurrence of injury (Y/N) and found that males received more injuries than females in both species. Also, subadults generally experienced frequent injury, as young individuals likely face challenges when competing for group membership and/or establishing rank. In Nepal gray langurs, males received 3 times more injuries during the mating season, suggesting strong competition for mates during this period, and females experienced more injuries before conception, suggesting competition to meet the nutritional requirements for reproduction. Unexpectedly, females in smaller groups received more injuries in Nepal gray langurs. Overall, these results indicate that injuries are most likely when fighting may aid in establishing group membership, achieving high rank, and reproducing. Future research should investigate the influence of injuries on fitness outcomes.
Impact of Intravenous Fluid Therapy on Survival Among Patients With Ebola Virus Disease: An International Multisite Retrospective Cohort Study
Authors: Aluisio Adam R , Yam Derrick , Peters Jillian L , Cho Daniel K , Perera Shiromi M , Kennedy Stephen B , Massaquoi Moses , Sahr Foday , Smit Michael A , Liu Tao , Levine Adam C 
Published: April 2019

Abstract

Background
Intravenous fluid (IVF) is a frequently recommended intervention in Ebola virus disease (EVD), yet its impact on patient outcomes remains unclear.

Methods
This retrospective cohort study evaluated patients with EVD admitted to 5 Ebola treatment units (ETUs) in West Africa. The primary outcome was the difference in 28-day survival between cases treated and not treated with IVF. To control for demographic and clinical factors related to both IVF exposure and survival, cases were compared using propensity score matching. To control for time-varying patient and treatment factors over the course of ETU care, a marginal structural proportional hazards model (MSPHM) with inverse probability weighting was used to assess for 28-day survival differences.

Results
Among 424 EVD-positive cases with data for analysis, 354 (83.5%) were treated with IVF at some point during their ETU admission. Overall, 146 (41.3%) cases treated with IVF survived, whereas 31 (44.9%) cases not treated with any IVF survived (P = .583). Matched propensity score analysis found no significant difference in 28-day survival between cases treated and not treated with IVF during their first 24 and 48 hours of care. Adjusted MSPHM survival analyses also found no significant difference in 28-day survival for cases treated with IVF (27.3%) compared to those not treated with IVF (26.9%) during their entire ETU admission (P = .893).

Conclusions
After adjustment for patient- and treatment-specific time-varying factors, there was no significant difference in survival among patients with EVD treated with IVF as compared to those not treated with IVF.
Short- vs. long-term dual antiplatelet therapy in secondary prevention for ischaemic stroke: a network metanalysis
Authors: Pugliese Francesca , Arasaratnam Punitha , Moellenberg Marcus , Dani Sourbha 
Published: April 2019

Abstract

Aims
This review aimed to compare the efficacy and safety of short-term (≤3 months) and long-term (≥1 year) dual-antiplatelet therapy (DAPT) in secondary prevention for ischaemic stroke.

Methods and results
We searched MEDLINE, EMBASE (Ovid), PubMed, Cochrane Library, ClinicalTrials.gov, and Google Advanced Search for randomized controlled trials. The population consisted of patients with recent ischaemic stroke or transient ischaemic attack. The intervention was DAPT with a combination of aspirin, clopidogrel, and dipyridamole compared to either aspirin or clopidogrel in monotherapy. The primary outcome was the rate of all recurrent stroke (ischaemic and haemorrhagic). Secondary outcomes were ischaemic stroke, all bleeding, severe bleeding, all-cause death, cardiovascular death, and myocardial infarction. Data were pooled by network metanalysis and pairwise metanalyses. Sixteen studies with 55 261 participants were included. Compared to aspirin, DAPT with aspirin clopidogrel decreased the risk of recurrent stroke [short-term odds ratio (OR) 0.67, 95% confidence interval (CI) 0.58–0.77; long-term OR 0.84, 95% CI 0.70–1.01] at the expense of increased risk of bleeding (short-term OR 1.76, 95% CI 1.26–2.46; long-term OR 2.25, 95% CI 1.97–2.57). Dual antiplatelet therapy with aspirin clopidogrel and clopidogrel in monotherapy had similar long-term risk of recurrent stroke (OR 0.98, 95% CI 0.83–1.14), but DAPT was associated with increased risk of bleeding (OR 2.77, 95% CI 2.21–3.46). Network metanalysis showed that short-term aspirin clopidogrel DAPT had the best risk-benefit profile, followed by long-term aspirin clopidogrel DAPT and clopidogrel alone. Aspirin dipyridamole DAPT was less effective.

Conclusion
Short-term DAPT had better risk-benefit profile than long-term DAPT.
Associations of Impaired Renal Function With Declines in Muscle Strength and Muscle Function in Older Men: Findings From the CHAMP Study
Authors: Toyama Tadashi , van den Broek-Best Oliver , Ohkuma Toshiaki , Handelsman David , Waite Louise M , Seibel Markus J , Cumming Robert , Naganathan Vasi , Sherrington Cathie , Hirani Vasant , Wang Amanda Y 
Published: April 2019

Abstract

Background
Advanced kidney disease is associated with reduced muscle strength and physical performance. However, associations between early stages of renal impairment and physical outcomes are unclear.

Methods
The Concord Health and Ageing in Men Project is a prospective study of 1,705 community-dwelling men aged 70 years and older. Participants with estimated glomerular filtration rate (eGFR) more than 30 mL/min/1.73 m2 were included and further divided into four eGFR categories. Physical parameters including grip strength, gait speed, appendicular lean mass (ALM, a sum of skeletal mass of arms and legs), ALM adjusted for body mass index (ALMBMI), and muscle function (measured using grip strength divided by arm lean mass) were assessed at both baseline and 5-year follow-up. Associations between kidney function and changes in physical parameters were analyzed using linear and logistic regression models.

Results
Our study included 789 men with a median age of 75 years and median eGFR of 72 mL/min/1.73 m2 at baseline. Over 5 years, grip strength, gait speed, ALMBMI, and muscle function all declined in the whole cohort, compared with baseline. The multivariable analyses showed that poorer renal function was associated with more rapid declines in grip strength, gait speed, and muscle function in participants with mild-to-moderate renal impairment (GFR category stage G3, eGFR < 60 mL/min/1.73 m2) (p = .01, p < .01, p = .02, respectively) but less so in those with eGFR more than 60 mL/min/1.73 m2, whereas eGFR category did not have a significant impact on declines in ALMBMI. These results remained unchanged with or without adjustment for age.

Conclusions
In community-dwelling older men, mild-to-moderate renal impairment at baseline was associated with declines in grip strength, gait speed, and muscle function over time despite preservation of muscle mass.
Use of 3-dimensional computed tomography for planning a complex sleeve bronchoplasty with total parenchyma-sparing resection of a carcinoid tumour in the right main bronchus
Authors: Betser Léa , De Wolf Julien , Glorion Matthieu , Chapelier Alain 
Published: April 2019

Abstract
Bronchoplasty is frequently required for radical resection of central typical carcinoid tumours. As sleeve bronchoplasty can be a complex procedure, an accurate evaluation of the tumour location is mandatory. Although the endobronchial part of the tumour can be easily evaluated by bronchoscopy, the exo-bronchial part is difficult to analyse with a standard computed tomography (CT) scan. A three-dimensional (3D) CT scan could be used to identify this exo-bronchial component of the tumour when planning a reconstruction. Herein, we present a case of a 59-year-old woman with a typical central carcinoid tumour of the right main bronchus. After 3D modelling, we successfully performed a total parenchyma-sparing resection with an intermedius bronchus reimplantation into the carina associated with the right upper bronchus anastomosis in the lateral trachea. The follow-up was uneventful. An endoscopy at 3 months showed excellent results.
Human Cytomegalovirus Genomes Sequenced Directly From Clinical Material: Variation, Multiple-Strain Infection, Recombination, and Gene Loss
Authors: Suárez Nicolás M , Wilkie Gavin S , Hage Elias , Camiolo Salvatore , Holton Marylouisa , Hughes Joseph , Maabar Maha , Vattipally Sreenu B , Dhingra Akshay , Gompels Ursula A , Wilkinson Gavin W G , Baldanti Fausto , Furione Milena , Lilleri Daniele , Arossa Alessia , Ganzenmueller Tina , Gerna Giuseppe , Hubáček Petr , Schulz Thomas F , Wolf Dana , Zavattoni Maurizio , Davison Andrew J 
Published: April 2019

AbstractThe genomic characteristics of human cytomegalovirus (HCMV) strains sequenced directly from clinical pathology samples were investigated, focusing on variation, multiple-strain infection, recombination, and gene loss. A total of 207 datasets generated in this and previous studies using target enrichment and high-throughput sequencing were analyzed, in the process enabling the determination of genome sequences for 91 strains. Key findings were that (i) it is important to monitor the quality of sequencing libraries in investigating variation; (ii) many recombinant strains have been transmitted during HCMV evolution, and some have apparently survived for thousands of years without further recombination; (iii) mutants with nonfunctional genes (pseudogenes) have been circulating and recombining for long periods and can cause congenital infection and resulting clinical sequelae; and (iv) intrahost variation in single-strain infections is much less than that in multiple-strain infections. Future population-based studies are likely to continue illuminating the evolution, epidemiology, and pathogenesis of HCMV.
N-acetylcysteine blocks SOS induction and mutagenesis produced by fluoroquinolones in Escherichia coli
Authors: Rodríguez-Rosado Ana I , Valencia Estela Ynés , Rodríguez-Rojas Alexandro , Costas Coloma , Galhardo Rodrigo S , Rodríguez-Beltrán Jerónimo , Blázquez Jesús 
Published: April 2019

AbstractBackgroundFluoroquinolones such as ciprofloxacin induce the mutagenic SOS response and increase the levels of intracellular reactive oxygen species (ROS). Both the SOS response and ROS increase bacterial mutagenesis, fuelling the emergence of resistant mutants during antibiotic treatment. Recently, there has been growing interest in developing new drugs able to diminish the mutagenic effect of antibiotics by modulating ROS production and the SOS response.ObjectivesTo test whether physiological concentrations of N-acetylcysteine, a clinically safe antioxidant drug currently used in human therapy, is able to reduce ROS production, SOS induction and mutagenesis in ciprofloxacin-treated bacteria without affecting antibiotic activity.MethodsThe Escherichia coli strain IBDS1 and its isogenic mutant deprived of SOS mutagenesis (TLS−) were treated with different concentrations of ciprofloxacin, N-acetylcysteine or both drugs in combination. Relevant parameters such as MICs, growth rates, ROS production, SOS induction, filamentation and antibiotic-induced mutation rates were evaluated.ResultsTreatment with N-acetylcysteine reduced intracellular ROS levels (by ∼40%), as well as SOS induction (by up to 75%) and bacterial filamentation caused by subinhibitory concentrations of ciprofloxacin, without affecting ciprofloxacin antibacterial activity. Remarkably, N-acetylcysteine completely abolished SOS-mediated mutagenesis.ConclusionsCollectively, our data strongly support the notion that ROS are a key factor in antibiotic-induced SOS mutagenesis and open the possibility of using N-acetylcysteine in combination with antibiotic therapy to hinder the development of antibiotic resistance.
Trends and correlates of antimicrobial use in broiler and turkey farms: a poultry company registry-based study in Italy
Authors: Caucci Claudia , Di Martino Guido , Dalla Costa Alessandro , Santagiuliana Manuel , Lorenzetto Monica , Capello Katia , Mughini-Gras Lapo , Gavazzi Luigi , Bonfanti Lebana 
Published: April 2019

Abstract

Background
Antimicrobial usage (AMU) in livestock plays a key role in the emergence and spread of antimicrobial resistance. Analysis of AMU data in livestock is therefore relevant for both animal and public health.

Objectives
To assess AMU in 470 broiler and 252 turkey farms of one of Italy’s largest poultry companies, accounting for around 30% of national poultry production, to identify trends and risk factors for AMU.

Methods
Antimicrobial treatments administered to 5827 broiler and 1264 turkey grow-out cycles in 2015–17 were expressed as DDDs for animals per population correction unit (DDDvet/PCU). A retrospective analysis was conducted to examine the effect of geographical area, season and prescribing veterinarian on AMU. Management and structural interventions implemented by the company were also assessed.

Results
AMU showed a 71% reduction in broilers (from 14 to 4 DDDvet/PCU) and a 56% reduction in turkeys (from 41 to 18 DDDvet/PCU) during the study period. Quinolones, macrolides and polymyxins decreased from 33% to 6% of total AMU in broilers, and from 56% to 32% in turkeys. Broiler cycles during spring and winter showed significantly higher AMU, as well as those in densely populated poultry areas. Different antimicrobial prescribing behaviour was identified among veterinarians.

Conclusions
This study evidenced a decreasing trend in AMU and identified several correlates of AMU in broilers and turkeys. These factors will inform the design of interventions to further reduce AMU and therefore counteract antimicrobial resistance in these poultry sectors.
Distribution of Recent non-marine ostracods in Icelandic lakes, springs, and cave pools
Authors: Alkalaj Jovana , Hrafnsdottir Thora , Ingimarsson Finnur , Smith Robin J , Kreiling Agnes-Katharina , Mischke Steffen 
Published: April 2019

AbstractOstracods in Icelandic freshwaters have seldom been researched, with the most comprehensive record from the 1930s. There is a need to update our knowledge of the distribution of ostracods in Iceland as they are an important link in these ecosystems as well as good candidates for biomonitoring. We analysed 25,005 ostracods from 44 lakes, 14 springs, and 10 cave pools. A total of 16 taxa were found, of which seven are new to Iceland. Candona candida (Müller, 1776) is the most widespread species, whereas Cytherissa lacustris (Sars, 1863) and Cypria ophtalmica (Jurine, 1820) are the most abundant, showing great numbers in lakes. Potamocypris fulva (Brady, 1868) is the dominant species in springs. While the fauna of lakes and springs are relatively distinct from each other, cave pools host species that are common in both lakes and springs. Icelandic non-marine ostracods include mostly generalist species, as well as species adapted to cold climates and resemble those of other north European countries while sharing very few species with the North American Arctic. Iceland is experiencing impacts from climate change and a booming tourism. It is possible to use selected freshwater ostracods as biomonitoring tools by constructing a detailed database of these species.
Effect of Plant Essential Oils and Their Major Constituents on Cypermethrin Tolerance Associated Detoxification Enzyme Activities in Spodoptera litura (Lepidoptera: Noctuidae)
Authors: Ruttanaphan Torranis , Pluempanupat Wanchai , Aungsirisawat Chutikan , Boonyarit Polnarong , Goff Gaelle Le , Bullangpoti Vasakorn 
Published: April 2019

Abstract
Essential oils are well known to act as biopesticides. This research evaluated the acute toxicity and synergistic effect of essential oil compounds in combination with cypermethrin against Spodoptera litura Fabricius (Lepidoptera: Noctuidae). The effects of distillation extracts of essential oils from Alpinia galanga Zingiberaceae (Zingiberales) rhizomes and Ocimum basilicum Lamiaceae (Lamiales) leaves; one of their primary essential oil compounds 1,8-cineole; and linalool were studied on second-instar S. litura by topical application under laboratory conditions. The results showed that A. galanga had the highest control efficiency, whereas1,8-cineole provided a moderate efficacy. The mixtures of linalool, 1,8-cineole, O. basilicum, or A. galanga with cypermethrin were synergistic on mortality. Activity measurements of the main detoxification enzymes show that linalool and 1,8-cineole inhibit the activity of cytochromes P450 and carboxylesterases, which could explain their synergistic effect. Based on our results, the use of these mixtures represents an ideal eco-friendly approach, helping to manage cypermethrin resistance of S. litura.
Aberrant alternative splicing in breast cancer
Authors: Yang Quan , Zhao Jinyao , Zhang Wenjing , Chen Dan , Wang Yang 
Published: April 2019

Abstract
Alternative splicing is critical for human gene expression regulation, which plays a determined role in expanding the diversity of functional proteins. Importantly, alternative splicing is a hallmark of cancer and a potential target for cancer therapeutics. Based on the statistical data, breast cancer is one of the top leading causes of cancer-related deaths in women worldwide. Strikingly, alternative splicing is closely associated with breast cancer development. Here, we seek to provide a general review of the relationship between alternative splicing and breast cancer. We introduce the process of alternative splicing and its regulatory role in cancers. In addition, we highlight the functions of aberrant alternative splicing and mutations of splicing factors in breast cancer progression. Moreover, we discuss the role of alternative splicing in cancer drug resistance and the potential of being targets for cancer therapeutics.
CT-based radiomic signatures for prediction of pathologic complete response in esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy
Authors: Yang Zhining , He Binghui , Zhuang Xinyu , Gao Xiaoying , Wang Dandan , Li Mei , Lin Zhixiong , Luo Ren 
Published: April 2019

Abstract
The objective of this study was to build models to predict complete pathologic response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC) patients using radiomic features. A total of 55 consecutive patients pathologically diagnosed as having ESCC were included in this study. Patients were divided into a training cohort (44 patients) and a testing cohort (11 patients). The logistic regression analysis using likelihood ratio forward selection was performed to select the predictive clinical parameters for pCR, and the least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomic predictors in the training cohort. Model performance in the training and testing groups was evaluated using the area under the receiver operating characteristic curves (AUC). The multivariate logistic regression analysis identified no clinical predictors for pCR. Thus, only radiomic features selected by LASSO were used to build prediction models. Three logistic regression models for pCR prediction were developed in the training cohort, and they were able to predict pCR well in both the training (AUC, 0.84–0.86) and the testing cohorts (AUC, 0.71–0.79). There were no differences between these AUCs. We developed three predictive models for pCR after nCRT using radiomic parameters and they demonstrated good model performance.