bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of intended and relative dose intensity of R‐CHOP in a large, consecutive cohort of elderly diffuse large B‐cell lymphoma patients treated with curative intent: no difference in cumulative incidence of relapse comparing patients by age
Authors: Eyre T. A. , Martinez‐Calle N. , Hildyard C. , Eyre D. W. , Plaschkes H. , Griffith J. , Wolf J. , Fields P. , Gunawan A. , Oliver R. , Djebbari F. , Booth S. , McMillan A. , Fox C. P. , Bishton M. J. , Collins G. P. , Hatton C. S. R. 
Published: February 2019

AbstractBackgroundThe increasing incidence of diffuse large B‐cell lymphoma (DLBCL) in ageing populations places a significant burden on healthcare systems. Co‐morbidity, frailty, and reduced organ and physiological reserve contribute to treatment‐related complications. The optimal dose intensity of R‐CHOP to optimize outcome across different ages with variable frailty and comorbidity burden is unclear.Objectives and MethodsWe examined the influence of intended (IDI) and relative (RDI) dose intensity of the combination of cyclophosphamide and doxorubicin, age and comorbidity on outcomes for DLBCL patients ≥70 years in a representative, consecutive cohort across eight UK centres (2009–2018). We determined predictors of survival using multivariable Cox regression, and predictors of recurrence before death using competing risks regression.ResultsPorgression‐free survival (PFS) and overall survival (OS) were significantly inferior in patients ≥80 vs. 70–79 years (P < 0.001). In contrast, 2‐year cumulative relapse incidence, when accounting for non‐relapse mortality as a competing risk, was no different between 70–79 vs. ≥80 years (P = 0.27) or comorbidity status (CIRS‐G: 0–6 vs. >6) (P = 0.27). In 70–79 years, patients with an IDI ≥80% had a significantly improved PFS and OS (P < 0.001) compared to IDI < 80%. Conversely, in patients ≥80 years, there was no difference in PFS (P = 0.88) or OS (P = 0.75) according to IDI <80% vs. ≥80%. On multivariable analysis, when comparing by age, there was a significantly higher cumulative relapse rate for patients aged 70–79 years with an IDI <80% (vs. >80%) (P = 0.04) but not for patients ≥80 years comparing IDI (P = 0.32).Conclusion‘R‐mini‐CHOP' provides adequate lymphoma‐specific disease control and represents a reasonable treatment option in elderly patients ≥80 years aiming for cure.
n‐3 polyunsaturated fatty acids provoke a specific transcriptional profile in rabbit adipose‐derived stem cells in vitro
Authors: Vackova Eкaterina , Bosnakovski Darko , Bjørndal Bodil , Yonkova Penka , Grigorova Natalia , Ivanova Zhenya , Penchev Georgi , Simeonova Galina , Miteva Lyuba , Milanova Anelya , Vachkova Tatyana , Stanilova Spaska , Penchev Georgiev Ivan 
Published: February 2019

AbstractAdipose‐derived stem cells (ADSCs) possess multipotent properties, and their proper functionality is essential for further development of metabolic disorders. In the current study, we explored the impact of two n‐3 LC‐PUFAs (long‐chain polyunsaturated fatty acids, DHA—docosahexaenoic; C22:6, and EPA—eicosapentaenoic; C20:5) on a specific profile of lipolytic‐related gene expressions in the in vitro‐differentiated subcutaneous and visceral ADSCs from rabbits. The subcutaneous and visceral ADSCs were obtained from 28‐day‐old New Zealand rabbits. The primary cells were cultured up to passage 4 and were induced for adipogenic differentiation. Thereafter, the differentiated cells were treated with 100 µg EPA or DHA for 48 hr. The total mRNA was isolated and target genes expression evaluated by real‐time RCR. The results demonstrated that treatment of rabbit ADSCs with n‐3 PUFAs significantly enhanced mRNA expression of Perilipin A, while the upregulation of leptin and Rab18 genes was seen mainly in ADSCs from visceral adipose tissue. Moreover, the EPA significantly enhanced PEDF (Pigment Derived Epithelium Factor) mRNA expression only in visceral cells. Collectively, the results suggest activation of an additional lipolysis pathway most evident in visceral cells. The data obtained in our study indicate that in vitro EPA up‐regulates the mRNA expression of the studied lipolysis‐associated genes stronger than DHA mainly in visceral rabbit ADSCs.
Safety first: seasonal and diel habitat selection patterns by red deer in a contrasted landscape
Authors: Fattebert J. , Morelle K. , Jurkiewicz J. , Ukalska J. , Borkowski J. 
Published: February 2019

AbstractSpatially heterogeneous landscapes provide solutions to the forage‐safety trade‐off when animals can access risky but energetically rewarding patches, or safer but resource‐poor patches. It can be advantageous for an animal to secure access to habitat heterogeneity at a broader scale in order to be able to dynamically adjust finer scale habitat use through time. We tested the hypothesis of a forage‐safety trade‐off optimization tactic in a hunted red deer (Cervus elaphus) population following a large accidental forest fire. We used telemetry data and fitted resource selection functions at the second‐ and third‐order scales. We then integrated the order‐specific probabilities into single, all‐in‐one multi‐level layers that synthetically captured the habitat selection patterns across scales by informing landscape‐scale annual habitat selectivity with finer within‐home‐range seasonal and diel processes. At the landscape scale, red deer anchored their home‐range at the interface of the disturbed and undisturbed patches, thereby securing habitat heterogeneity. This consequently enabled them to modulate within‐home‐range habitat selection depending on the season and the time of the day. In both seasons, red deer consistently used the burnt area for cover more during the day, and foraged in the unburnt forest and open fields at night. Interestingly there were no major seasonal differences in this diel habitat selection patterns. Increased mortality risk during the hunting season did not substantially change their spatial behaviour. We conclude that year‐round avoidance of non‐lethal human disturbance is the main driver of red deer habitat use in this system.
How light conditions influence theoretical pelagic to benthic primary production ratios in small lakes
Authors: Cremona Fabien , Laas Alo , Kõiv Toomas , Sepp Margot , Nõges Peeter , Nõges Tiina 
Published: February 2019

AbstractTheoretical pelagic primary production of phytoplankton and benthic primary production of periphyton were modelled for two small lakes in Estonia (Northeast Europe). Although located only 500 m apart, the water colour and light attenuation of these two lakes differed markedly. The Secchi depth (SD) in the clear‐water lake was 4.5 m and only 0.47 m in the dark‐water lake. The total phosphorus (TP) concentrations were, respectively, 15 μg/l and 28 μg/l. An empirical model whose inputs were morphometric, light conditions and dissolved organic carbon parameters obtained from in situ measurements was employed for the present study. The model calculated primary production with a time‐step of 10 min, and a spatial resolution of 10 cm, from sunrise to sunset and from lake surface to lake bottom. The primary production of periphyton and phytoplankton was almost equal in the clear lake, whereas only phytoplankton contributed to whole‐lake primary production in the dark lake because of the stronger light attenuation in the water column. The results of the present study indicated the depth‐distribution profiles differed dramatically between the two lakes. The clear lake had a deep, U‐shaped curve, with the productive layer reaching considerable depth soon after sunrise and maintaining a similar profile throughout the light hours. In contrast, the dark lake production declined rapidly with increasing depth, whereas the profile changed over the day reaching the greatest depth at noon.
“There Is a Big Question Mark”: Managing Ambiguity in a Moroccan Maternity Ward
Authors: Newman Jess Marie 
Published: February 2019

AbstractIn Morocco, where extramarital sex and abortion are illegal, single mothers’ ambiguous status before the law inflects medical decision‐making. Leaky boundaries between the court and the hospital required doctors and administrators to work with multiple forms of documentation while anticipating external surveillance. Gaps between everyday experience and legalized forms of identity created confusion across multiple institutions. When discussing single mothers, hospital staff often spoke of “question marks” that flagged tensions between legibility and liability, disappearance and documentation. Managing question marks ramified surveillance and categorization. Ultimately, however, attempts to administratively resolve single mothers’ ambiguity created gaps and inconsistencies that allowed vulnerable patients to disappear from view.
Upper esophageal sphincter metrics on high‐resolution manometry differentiate etiologies of esophagogastric junction outflow obstruction
Authors: Blais Pierre , Bennett Michael C. , Gyawali C. Prakash 
Published: February 2019

AbstractBackgroundUpper esophageal sphincter (UES) metrics on high‐resolution manometry (HRM), particularly nadir UES residual pressure (UES‐RP), are abnormal in achalasia and may help characterize the underlying mechanism or predict management outcome in esophagogastric junction outflow obstruction (EGJOO).MethodsA database of consecutive patients undergoing esophageal HRM from 2008 to 2013 yielded 134 patients (59.8 ± 1.4 years, 68% F) with EGJOO. Final clinical diagnoses and treatment response were extracted from chart review. Esophageal body, UES, and lower esophageal sphincter (LES) metrics were compared between EGJOO and asymptomatic healthy controls (n = 16, 27.7 ± 0.7 years, 56% F). Logistic regression evaluated differences between HRM metrics amongst etiologies of EGJOO grouped into motor versus mechanical disorders.Key resultsDistal contractile integral, distal latency, and nadir UES‐RP were significantly different between EGJOO subgroups (P ≤ 0.01 for each comparison), but only nadir UES‐RP remained independently predictive of subgroups (adjusted odds ratio 1.15, 95% confidence intervals 1.05‐1.27, P < 0.01). Nadir UES‐RP was highest in achalasia variants, and lowest in mechanical EGJOO and controls (P < 0.001). Of 19 patients who underwent LES myotomy, durable benefit was reported by 68.4% over mean 3.6 years of follow‐up. Significantly higher nadir UES‐RP was noted with symptom relief (3.4 vs −0.7 mm Hg with symptom recurrence, 95% confidence intervals of difference = 1.35‐6.83). A threshold UES‐RP of ≥2.0 mm Hg yielded a sensitivity of 84.6% and specificity of 83.3% in predicting symptom resolution following myotomy.Conclusions and inferencesNadir UES‐RP offers clues to differentiation of subtypes within EGJOO and may predict symptom outcome from myotomy.
The challenges to public health nurse practice in rural Ireland
Authors: Farrelly Tom , Flaherty Sinéad , Healy Hannah 
Published: February 2019

AbstractObjectivesThe primary objective was to understand the contemporary public health nurse's (PHN) role and the issues that they face working in rural Ireland.Design and SampleThis study was based on an ethnographic approach with 13 PHNs working in rural areas in the South West of Ireland.MeasurementsA combination of solicited diaries and semi‐structured interviews referred to as the diary/interview method were employed. Diaries were used by the PHNs to record their working day on a staggered basis from February to April 2017 with the subsequent interviews carried out in June and July 2017.ResultsWorking as a PHN in a rural area presented a number of issues such as time spent on traveling as a result of geographical disparity & poor road networks; client transport issues; a sense of working in isolation; communication issues with respect to computer/tablet hardware availability, mobile phone and broadband connectivity and the availability of, and the physical access to services.ConclusionPHNs operating in rural communities face a distinct set of challenges that they have a limited ability to address. Legislators, health care providers and policymakers need to create a supportive environment that helps address these challenges in Ireland.
Leishmania braziliensis isolated from disseminated leishmaniasis patients downmodulate neutrophil function
Authors: Cardoso Thiago , Bezerra Caroline , Medina Lilian Silva , Ramasawmy Rajendranath , Scheriefer Albert , Bacellar Olívia , de Carvalho Edgar M. 
Published: February 2019

SummaryAimsThe polymorphism observed in Leishmania braziliensis is associated with different clinical forms of leishmaniasis. Neutrophils (PMNs) participate in the pathogenesis of leishmania infection, and here, we evaluate neutrophil function after infection with isolates of L. braziliensis from cutaneous leishmaniasis (CL) or disseminated leishmaniasis (DL) patients.Methods and resultsNeutrophils from 30 healthy subjects (HS) were infected with isolates of L. (V.) braziliensis obtained from three CL and three DL patients. They were infected at the ratio of 3:1 parasites per neutrophil, and leishmania uptake was evaluated by microscopy. The neutrophil activation markers and oxidative burst by expression of dihidrorhodamine (DHR) were evaluated by flow cytometry and cytokine production by ELISA. The frequency of infected cells and the number of amastigotes were higher in neutrophils infected with CL isolates compared to DL isolates (P < 0.05). The DHR and CD66b expression after infection with DL isolate was lower than with CL isolates. There was no difference regarding chemokine production.ConclusionThe L. (V.) braziliensis isolates of DL induced lower respiratory burst and neutrophils activation markers compared with CL isolates which may contribute to parasite survival and dissemination in DL patients.
The Nrf2 pathway is required for intracellular replication ofToxoplasma gondiiin activated macrophages
Authors: Pang Yu , Zhang Zhaoxia , Chen Yuntong , Cao Shinuo , Yang Xiuqin , Jia Honglin 
Published: February 2019

SummaryReactive oxygen species (ROS) produced by oxidases and nonenzymatic sources are important for host defence against intracellular pathogens. In this study, we knocked out the Nrf2 gene inRAW264.7 cells using theCRISPR/Cas9 system and investigated the antioxidant effects of the Nrf2 pathway in the cells stimulated byIFN‐γ andTNF‐α. The results indicated that the Nrf2 signalling pathway is necessary for maintaining redox homeostasis in activatedRAW264.7 cells. Inactivation of Nrf2 impaired parasite growth. We also found that p62 contributes to Nrf2‐mediated pathways involved inT gondiiinfection. These findings suggest that the Nrf2/Keap1 pathway may be targeted to prevent and treat toxoplasmosis.
Stochastic Counterfactual Risk Analysis for the Vulnerability Assessment of Cyber‐Physical Attacks on Electricity Distribution Infrastructure Networks
Authors: Oughton Edward J. , Ralph Daniel , Pant Raghav , Leverett Eireann , Copic Jennifer , Thacker Scott , Dada Rabia , Ruffle Simon , Tuveson Michelle , Hall Jim W 
Published: February 2019

AbstractIn December 2015, a cyber‐physical attack took place on the Ukrainian electricity distribution network. This is regarded as one of the first cyber‐physical attacks on electricity infrastructure to have led to a substantial power outage and is illustrative of the increasing vulnerability of Critical National Infrastructure to this type of malicious activity. Few data points, coupled with the rapid emergence of cyber phenomena, has held back the development of resilience analytics of cyber‐physical attacks, relative to many other threats. We propose to overcome data limitations by applying stochastic counterfactual risk analysis as part of a new vulnerability assessment framework. The method is developed in the context of the direct and indirect socioeconomic impacts of a Ukrainian‐style cyber‐physical attack taking place on the electricity distribution network serving London and its surrounding regions. A key finding is that if decision‐makers wish to mitigate major population disruptions, then they must invest resources more‐or‐less equally across all substations, to prevent the scaling of a cyber‐physical attack. However, there are some substations associated with higher economic value due to their support of other Critical National Infrastructures assets, which justifies the allocation of additional cyber security investment to reduce the chance of cascading failure. Further cyber‐physical vulnerability research must address the tradeoffs inherent in a system made up of multiple institutions with different strategic risk mitigation objectives and metrics of value, such as governments, infrastructure operators, and commercial consumers of infrastructure services.
“Old age” as a social location: Theorizing institutional processes, cultural expectations, and interactional practices
Authors: Barken Rachel 
Published: February 2019

AbstractThe graying of societies and growing inequality call for increased attention to age relations and their implications for power, status, and constraint in late life. In this paper, I argue old age is a distinct—and devalued—social location that exists amid intersecting relations of inequality. Using an integrative approach, I synthesize selected sociological research on the institutional processes, cultural expectations, and interactional practices underlying the social construction of old age. I then review research in the areas of family care work and employment to illustrate some empirical contexts where age relations intersect with gender, class, race, and ethnicity to structure divergent opportunities and constraints among older people. This paper maps out significant theoretical and substantive signposts in the sociology of old age to build connections across levels of analysis, and to provide a nuanced, comprehensive approach to patterned inequalities in late life.
Investigation of assumptions and approximations in the virtual fields method for a viscoplastic material model
Authors: Jones Elizabeth M. C. , Karlson Kyle N. , Reu Phillip L. 
Published: February 2019

AbstractThe Virtual Fields Method (VFM) is an inverse technique used for parameter estimation and calibration of constitutive models. Many assumptions and approximations—such as plane stress, incompressible plasticity, and spatial and temporal derivative calculations—are required to use VFM with full‐field deformation data, for example, from Digital Image Correlation (DIC). This work presents a comprehensive discussion of the effects of these assumptions and approximations on parameters identified by VFM for a viscoplastic material model for 304L stainless steel. We generated synthetic data from a Finite‐Element Analysis (FEA) in order to have a reference solution with a known material model and known model parameters, and we investigated four cases in which successively more assumptions and approximations were included in the data. We found that VFM is tolerant to small deviations from the plane stress condition in a small region of the sample, and that the incompressible plasticity assumption can be used to estimate thickness changes with little error. A local polynomial fit to the displacement data was successfully employed to compute the spatial displacement gradients. The choice of temporal derivative approximation (i.e., backwards difference versus central difference) was found to have a significant influence on the computed rate of deformation and on the VFM results for the rate‐dependent model used in this work. Finally, the noise introduced into the displacement data from a stereo‐DIC simulator was found to have negligible influence on the VFM results. Evaluating the effects of assumptions and approximations using synthetic data is a critical first step for verifying and validating VFM for specific applications. The results of this work provide the foundation for confidently using VFM for experimental data.
Soil available potassium affected by rice straw incorporation and potassium fertilizer application under a rice–oilseed rape rotation system
Authors: Zhu Dandan , Zhang Jianglin , Wang Zheng , Muhammad Rizwan Khan , Lu Jianwei , Li Xiaokun 
Published: February 2019

AbstractData from 147 field trials were collected to study the influence of straw incorporation on soil potassium (K) under an intensive rice–oilseed rape rotation system, while pot experiments were conducted to evaluate the effects of rice straw incorporation on soil K availability. A significant correlation was observed between the soil available K and the relative yield (RRY) and the relative K uptake (RKU) of oilseed rape, with R2 values ranging from 0.07 to 0.08 and from 0.10 to 0.11, respectively, when data were fitted to a logarithmic equation model. In approximately 30% of trials, RRY reached 90%, while soil test available K values were below the critical limit, indicating that soil K values at the time of sampling (within 1 week of rice harvest) underestimated the actual soil K supply capacity. The pot experiment results showed that soil available K was affected by straw incorporation and soil type in the fallow period. The NH4OAc‐K and NaBPh4‐K concentrations of soils increased at first, and then, plateaued after 28 days. Straw incorporation significantly influenced the critical soil K concentration, which is important for making accurate K fertilizer recommendation. These results suggested that straw K should be seriously considered in making K fertilizer recommendations. Extending the sampling time from 1 to 3 weeks after the harvesting of rice to stabilize the effects of straw incorporation may help achieve a more accurate evaluation of soil available K.
Genetic diversity and population structure of Plasmodium falciparum in Kenyan–Ugandan border areas
Authors: Nderu David , Kimani Francis , Karanja Evaline , Thiong'o Kelvin , Akinyi Maureen , Too Edwin , Chege William , Nambati Eva , Wangai Laura N. , Meyer Christian G. , Velavan Thirumalaisamy P. 
Published: February 2019

SummaryKenya has, in the last decade, made tremendous progress in the fight against malaria. Nevertheless, continued surveillance of the genetic diversity and population structure of Plasmodium falciparum is required to refine malaria control and to adapt and improve elimination strategies. Twelve neutral microsatellite loci were genotyped in 201 P. falciparum isolates obtained from the Kenyan–Ugandan border (Busia) and from two inland malaria‐endemic sites situated in western (Nyando) and coastal (Msambweni) Kenya. Analyses were done to assess the genetic diversity (allelic richness and expected heterozygosity, [He]), multilocus linkage disequilibrium () and population structure. A similarly high degree of genetic diversity was observed among the three parasite populations surveyed (mean He = 0.76; P > 0.05). Except in Msambweni, random association of microsatellite loci was observed, indicating high parasite out‐breeding. Low to moderate genetic structure (FST = 0.022–0.076; P < 0.0001) was observed with only 5% variance in allele frequencies observed among the populations. This study shows that the genetic diversity of P. falciparum populations at the Kenyan–Ugandan border is comparable to the parasite populations from inland Kenya. In addition, high genetic diversity, panmixia and weak population structure in this study highlight the fitness of Kenyan P. falciparum populations to successfully withstand malaria control interventions.