bluuebunny/crossref_metadata_2025_split huggingface dataset:
CNS inflammation after natalizumab therapy for multiple sclerosis: A retrospective histopathological and CSF cohort study
Authors: Häusler Darius , Akgün Katja , Stork Lidia , Lassmann Hans , Ziemssen Tjalf , Brück Wolfgang , Metz Imke 
Published: May 2021

AbstractNatalizumab, a recombinant humanized monoclonal antibody directed against the α4 subunit of the integrins α4ß1 and α4ß7, has been approved for the treatment of active relapsing‐remitting MS. Although natalizumab is a highly beneficial drug that effectively reduces the risk of sustained disability progression and the rate of clinical relapses, some patients do not respond to it, and some are at higher risk of developing progressive multifocal leukoencephalopathy (PML). The histopathological effects after natalizumab therapy are still unknown. We, therefore, performed a detailed histological characterization of the CNS inflammatory cell infiltrate of 24 brain specimens from natalizumab treated patients, consisting of 20 biopsies and 4 autopsies and 21 MS controls. To complement the analysis, immune cells in blood and cerebrospinal fluid (CSF) of 30 natalizumab‐treated patients and 42 MS controls were quantified by flow cytometry. Inflammatory infiltrates within lesions were mainly composed of T cells and macrophages, some B cells, plasma cells, and dendritic cells. There was no significant difference in the numbers of T cells or macrophages and microglial cells in lesions of natalizumab‐treated patients as compared to controls. A shift towards cytotoxic T cells of a memory phenotype was observed in the CSF. Plasma cells were significantly increased in active demyelinating lesions of natalizumab‐treated patients, but no correlation to clinical disability was observed. Dendritic cells within lesions were found to be reduced with longer ongoing therapy duration. Our findings suggest that natalizumab does not completely prevent immune cells from entering the CNS and is associated with an accumulation of plasma cells, the pathogenic and clinical significance of which is not known. As B cells are considered to serve as a reservoir of the JC virus, the observed plasma cell accumulation and reduction in dendritic cells in the CNS of natalizumab‐treated patients may potentially play a role in PML development.
A method for assessing sustainability, with beef production as an example
Authors: Broom Donald M. 
Published: May 2021

ABSTRACTA comprehensive approach to decisions about the use of land and other world resources, taking full account of biological and other scientific information, is crucial for good decisions to be made now and in future. The sustainability of systems for producing food and other products is sometimes assessed using too narrow a range of component factors. A production system might be unsustainable because of adverse effects on a wide range of aspects of human welfare, animal welfare, or the environment. All factors should be included in sustainability evaluation, otherwise products or actions might be avoided without adequate consideration of key factors or of the diversity of production systems. A scoring method that is based on scientific information and potentially of general relevance is presented here, using beef production as a example with a review of each of its sustainability components. This includes an overall combined score and specific factors that make the system unacceptable for some consumers. The results show that, in this example, the sustainability of the best systems is very much better than that of the worst systems. By taking account of scores for a wide range of components of sustainability in comparing beef‐production systems, better quality policies about beef use can be formulated than when statements referring only to one system are considered. The least sustainable beef‐production systems are extensive grazing that causes land degradation and the use of feedlots or indoor housing with grain feeding. Semi‐intensive silvopastoral systems are the most sustainable beef‐production systems, and well‐managed pasture‐fed beef from areas where crop production is uneconomic is also sustainable. This simple, scientifically based scoring system could be modified to use positive as well as negative scores and is of value for policy makers, researchers, producers, organisations aiming to improve sustainability, and the general public.
Les théories sociologiques comme expression de l'appropriation culturelle, un point de vue critique
Authors: Hamel Jacques 
Published: May 2021

AbstractIn light of the importance assumed by the English language in the sociological orbit, this article seeks to show how certain theoretical currents induce epistemologies in national sociologies, to use the expression dear to Foucault, even epistemologies likely to compromise the explication of sociological subject matter of interest within francophone countries, for example. It can be shown that intersectionality and standpoint theory emerge from the “historical configuration” of Anglo‐Saxon countries like the United States, and particularly from the political and militant struggles known in this country, at the root of the political correctness, safe spaces and cultural appropriation that prevail today on American campuses. In conclusion, considerations on “epistemologically correct” sociological theory are exposed, with the intention of nuancing them on an epistemological level.
Values‐Alignment Messaging Boosts Adolescents’ Motivation to Control Social Media Use
Authors: Galla Brian M. , Choukas‐Bradley Sophia , Fiore Hannah M. , Esposito Michael V. 
Published: May 2021

Two preregistered experiments with 2,733 U.S. high school students (age range = 13–19 years) compared the impact of different messages on adolescents’ motivation to control social media use (SMU). A traditional message emphasized the benefits of avoiding SMU, whereas a values‐alignment message framed controlling SMU as being consistent with autonomy and social justice. Compared to no message or a traditional message, in both studies, a values‐alignment message led to greater motivation to control SMU immediately afterward, and in Study 2, awareness of “addictive” social media designs 3 months later. As hypothesized, values‐alignment messaging was more motivating for girls than boys. Results offer preliminary support for leveraging adolescents’ drives for autonomy and social justice to motivate self‐regulation of SMU.
Despite large choice of effective therapies: Individuals with psoriasis still seem undertreated
Authors: Pilz Anna Caroline , Zink Alexander , Schielein Maximilian C. , Hell Katharina , Romer Katrin , Hillmann Elena , Bäumer Daniel , Reinhardt Maximilian , Wagner Nicola 
Published: May 2021

SummaryBackground and objectivesDue to the development of new anti‐psoriatic drugs in combination with improved structures for implementation throughout Germany, the medical care of psoriasis patients has markedly improved. In this study we investigated the real‐life utilization of the health care system and identified reasons for dissatisfaction in affected individuals.Patients and methodsThis non‐interventional cross‐sectional study was conducted as an anonymous online survey from 12/2018 to 01/2019 in Germany. Participants with a self‐reported physician‐confirmed diagnosis of psoriasis and symptoms answered questions about their disease, its influence on daily life and their medical care.Results649 participants with a mean age of 42.5 ± 13.7 years and equal gender distribution (male: 50.2 %) were evaluated. 54.1 % received medical treatment at the time of the study, 45.9 % did not. Among the participants with medical care, 59.3 % were only moderately or less satisfied with their treatment. Reasons for dissatisfaction with the medication included lack of efficacy and side effects. Participants without medical treatment specified a physician’s lack of time as a main reason for not seeking medical help.ConclusionsDespite the availability of efficient therapeutic options in Germany, many individuals with psoriasis are not satisfied. This under‐treated group was identified as a new target population.
A combination of phenobarbital and the bumetanide derivative bumepamine prevents neonatal seizures and subsequent hippocampal neurodegeneration in a rat model of birth asphyxia
Authors: Johne Marie , Käufer Christopher , Römermann Kerstin , Gailus Björn , Gericke Birthe , Löscher Wolfgang 
Published: May 2021

AbstractObjectivesBumetanide was suggested as an adjunct to phenobarbital for suppression of neonatal seizures. This suggestion was based on the idea that bumetanide, by reducing intraneuronal chloride accumulation through inhibition of the Na‐K‐2Cl cotransporter NKCC1, may attenuate or abolish depolarizing γ‐aminobutyric acid (GABA) responses caused by birth asphyxia. However, a first proof‐of‐concept clinical trial failed. This could have had several reasons, including bumetanide's poor brain penetration, the wide cellular NKCC1 expression pattern in the brain, and problems with the general concept of NKCC1’s role in neonatal seizures. We recently replicated the clinical failure of bumetanide to potentiate phenobarbital's effect in a novel rat model of birth asphyxia. In this study, a clinically relevant dose (0.3 mg/kg) of bumetanide was used that does not lead to NKCC1‐inhibitory brain levels. The aim of the present experiments was to examine whether a much higher dose (10 mg/kg) of bumetanide is capable of potentiating phenobarbital in this rat model. Furthermore, the effects of the two lipophilic bumetanide derivatives, the ester prodrug N,N‐dimethylaminoethylester of bumetanide (DIMAEB) and the benzylamine derivative bumepamine, were examined at equimolar doses.MethodsIntermittent asphyxia was induced for 30 min by exposing male and female P11 rat pups to three 7 + 3 min cycles of 9% and 5% O2 at constant 20% CO2. All control pups exhibited neonatal seizures after the asphyxia.ResultsEven at 10 mg/kg, bumetanide did not potentiate the effect of a submaximal dose (15 mg/kg) of phenobarbital on seizure incidence, whereas a significant suppression of neonatal seizures was determined for combinations of phenobarbital with DIMAEB or, more effectively, bumepamine, which, however, does not inhibit NKCC1. Of interest, the bumepamine/phenobarbital combination prevented the neurodegenerative consequences of asphyxia and seizures in the hippocampus.SignificanceBoth bumepamine and DIMAEB are promising tools that may help to develop more effective lead compounds for clinical trials.
Conservation risks and portfolio effects in mixed‐stock fisheries
Authors: Moore Jonathan W. , Connors Brendan M. , Hodgson Emma E. 
Published: May 2021

AbstractFish biodiversity sustains the resilience and productivity of fisheries, yet this biodiversity can be threatened by overharvest and depletion in mixed‐stock fisheries. Thus, the biodiversity that provides benefits may also make sustainable resource extraction more difficult, a key challenge in fisheries management. We simulated a mixed‐stock fishery to explore relationships between different dimensions of biodiversity and fishery performance relative to conservation and fishery objectives. Different dimensions of biodiversity (number of stocks, evenness, asynchrony among stocks, heterogeneity in stock productivity) exacerbated trade‐offs between fishery and conservation objectives. For example, fisheries targeting stock‐complexes with greater asynchrony, and to a lesser extent richness, had greater stability in harvest through time but also greater risks of overfishing weak stocks and reduced yield compared to less biodiverse stock‐complexes. These trade‐offs were ameliorated by increasing management control—the capacity of fishery managers to harvest specific stocks. To explore these trade‐offs in real‐world fisheries, we contrasted the fishing and population status of individual stocks within three major mixed‐stock sockeye salmon (Oncorhynchus nerka, Salmonidae) fisheries—Bristol Bay, Fraser River, and Skeena River. In general, the fisheries with lower management control had individual stocks that were more often being over‐ or under‐fished, compared with those with higher management control, though variation among regions in biodiversity, scale of management, and magnitude of habitat alteration likely also contribute to these relationships. Collectively, our findings emphasize that there is a need to extract less or regulate better in order to conserve and benefit from biodiversity in fisheries and other natural resource management systems.
Comparative analysis of the pivotal studies of extended half‐life recombinant FVIII products for treatment of haemophilia A
Authors: Mannucci Pier Mannuccio , Cortesi Paolo Angelo , Di Minno Matteo Nicola Dario , Sanò Mario , Mantovani Lorenzo Giovanni , Di Minno Giovanni 
Published: May 2021

AbstractThe need to reduce the burden of injections, and improve adherence and clinical outcomes in haemophilia A led to the development of recombinant FVIII products endowed with an extended plasma half‐life (EHL‐rFVIII) in comparison with standard half‐life products (SHL‐rFVIII). Lack of head‐to‐head studies makes difficult to grasp the relative value of each treatment option. We conducted a combined evaluation of the individual pivotal trials in order to assess between‐product differences regarding the reported efficacy results and FVIII consumption. We evaluated 4 EHL‐rFVIII products available to treat patients with haemophilia A without inhibitors and also a SHL‐rFVIII as a comparator. In the frame of these clinical studies, all the EHL‐rFVIII products showed a decrease in the injection burden coupled with good clinical efficacy, even though there were between‐product differences in terms of reduction in injection frequencies. Further, between‐product differences in terms of weekly/yearly consumption of rFVIII expressed in IU/Kg were identified, suggesting a different economic impact for the different EHL‐rFVIII products in the context of comparable clinical efficacy. The present findings based upon the review of pivotal studies done in the frame of a highly selected clinical scenario should be integrated with real‐life data.
Dynamic space use of Andalusian rice fields by Lesser Black‐backed Gulls (Larus fuscus) is driven by flooding pattern
Authors: van Rees Charles B. , Aragonés David , Bouten Willem , Thaxter Chris B. , Stienen Eric W. M. , Bustamante Javier , Green Andy J. 
Published: May 2021

Research on the space use and behaviour of waterbirds yields important insights on human–wildlife interactions of ecological and societal importance under global change. The extent to which dynamic (within‐season) changes in anthropogenic landscapes affect these interactions is poorly understood. Lesser Black‐backed GullsLarus fuscusare prominent bio‐vectors of biological, synthetic and inorganic materials and have exhibited large increases in abundance in parts of southern Europe in recent decades. We combined GPS tracking, earth observation, accelerometry and field observations to study the space use of overwintering gulls in a mixed rice field landscape in Andalusia, southern Spain. We used Manly selectivity metrics, a common quantitative measurement of habitat selection, and classified remote sensing imagery directly to evaluate space use and habitat selection for these gulls and how it changed throughout the rice harvest cycle. Analysis of over 45 000 GPS fixes and 14 classified remotely sensed images from winter 2016/17 showed dynamic space use driven by the harvest‐related flooding across the rice harvest cycle. Prior to harvest, gulls foraged in rice paddies during the day and roosted in adjacent waterbodies (the River Guadalquivir and fish ponds) at night. During harvest, they spent nearly 100% of their daily cycle within the rice fields, foraging in harvested paddies and roosting in post‐harvest, flooded paddies. After harvest, they roosted in flooded paddies at night and foraged at landfills in the surrounding landscape. Gull space use at landscape and paddy scales was closely linked to dynamic land and water management over the rice agricultural cycle, illustrating how human activities influence the movements of ecologically important, human‐associated bio‐vectors such as gulls. The frequent early‐spring movement patterns of gulls between landfills and agricultural fields makes them an important bio‐transport link for potentially toxic materials and pathogens between waste sites and places where food is grown for human consumption.
Enzalutamide with androgen deprivation therapy in Japanese men with metastatic hormone‐sensitive prostate cancer: A subgroup analysis of the phase III ARCHES study
Authors: Iguchi Taro , Kimura Go , Fukasawa Satoshi , Suzuki Hiroyoshi , Uemura Hiroji , Nishimura Kazuo , Matsumoto Hiroaki , Yokomizo Akira , Armstrong Andrew J , Rosbrook Brad , Sugg Jennifer , Baron Benoit , Chen Lucy , Kunieda Futoshi , Stenzl Arnulf 
Published: May 2021

ObjectiveTo evaluate the efficacy and safety of enzalutamide plus androgen deprivation therapy in Japanese men with metastatic hormone‐sensitive prostate cancer.MethodsA post‐hoc analysis of the Japanese subgroup in the phase III, randomized, multinational ARCHES study (NCT02677896) was carried out. Patients with metastatic hormone‐sensitive prostate cancer were randomized to receive enzalutamide or a placebo, plus androgen deprivation therapy, stratified by disease volume and prior docetaxel therapy. The primary end‐point was radiographic progression‐free survival. Secondary end‐points included time to prostate‐specific antigen progression and overall survival.ResultsOf 1150 patients, 92 Japanese patients were randomized to enzalutamide (n = 36) or a placebo (n = 56), plus androgen deprivation therapy; none received prior docetaxel. Enzalutamide plus androgen deprivation therapy reduced the risk of radiographic progression or death in Japanese patients by 61% versus the placebo, similar to the overall population. Similar results were observed with secondary end‐points, showing clinical benefit of enzalutamide plus androgen deprivation therapy in Japanese patients. Overall survival data were immature. Grade 3–4 adverse events were reported in 47% and 25% of the enzalutamide and placebo groups, respectively. Nasopharyngitis, hypertension and abnormal hepatic function were reported more frequently in Japanese patients versus the overall population.ConclusionsEnzalutamide plus androgen deprivation therapy has clinical benefit with a tolerable safety profile in Japanese men with metastatic hormone‐sensitive prostate cancer, consistent with the overall population.
A century of BCG: Impact on tuberculosis control and beyond
Authors: Ahmed Asma , Rakshit Srabanti , Adiga Vasista , Dias Mary , Dwarkanath Pratibha , D’Souza George , Vyakarnam Annapurna 
Published: May 2021

AbstractBCG turns 100 this year and while it might not be the perfect vaccine, it has certainly contributed significantly towards eradication and prevention of spread of tuberculosis (TB). The search for newer and better vaccines for TB is an ongoing endeavor and latest results from trials of candidate TB vaccines such as M72AS01 look promising. However, recent encouraging data from BCG revaccination trials in adults combined with studies on mucosal and intravenous routes of BCG vaccination in non‐human primate models have renewed interest in BCG for TB prevention. In addition, several well‐demonstrated non‐specific effects of BCG, for example, prevention of viral and respiratory infections, give BCG an added advantage. Also, BCG vaccination is currently being widely tested in human clinical trials to determine whether it protects against SARS‐CoV‐2 infection and/or death with detailed analyses and outcomes from several ongoing trials across the world awaited. Through this review, we attempt to bring together information on various aspects of the BCG‐induced immune response, its efficacy in TB control, comparison with other candidate TB vaccines and strategies to improve its efficiency including revaccination and alternate routes of administration. Finally, we discuss the future relevance of BCG use especially in light of its several heterologous benefits.
Social innovations and the fight against poverty: An analysis of India's first prosocial P2P lending platform
Authors: Ravishankar M. N. 
Published: May 2021

AbstractProsocial P2P lending platforms are a novel and powerful example of a digital social innovation (DSI) in which the operating model relies primarily on digital technologies and the overarching focus is on the “social” aspect of the innovation. These platforms establish a virtual connection between low‐income individuals and lenders, helping the former access loans at low rates of interest. In realising their mission of fighting poverty, prosocial P2P lending platforms maintain a challenging hybrid – online and offline – focus. This paper explores how prosocial P2P lending platforms enact their hybrid orientation. It draws on an inductive qualitative study of Rang De, India's first prosocial P2P lending platform. The analysis highlights five clusters of actions: digital attention‐building, digital credibility‐building, digital empathy‐building, intermediary relationship‐building, and borrower relationship‐building. The paper argues that significant strengths on the online side help establish a sustainable business model. A willingness and commitment to maintain a high degree of engagement with the complex offline world of low‐income borrowers helps develop the model as an impactful social innovation.
A deep learning technique based flood propagation experiment
Authors: Hou Jingming , Li Xuan , Bai Ganggang , Wang Xinhong , Zhang Zongxiao , Yang Lu , Du Ying'en , Ma Yongyong , Fu Deyu , Zhang Xianguo 
Published: May 2021

AbstractThis work presents an experiment involving detailed fluvial flood propagation process. Comparing to the existing flood experiments which collect hydrodynamical data just at gauges, flood evolution process in river channel and flood plain is measured and temporal–spatial data are provided. In the experiment, three inflow patterns are considered to reflect the different severity of the floods. The flood propagation and inundation are captured by using an array of surveillance cameras. The images are pre‐processed by applying camera calibration method to correct the barrel distortion. A deep learning technique is introduced to automatically identify inundated area. The inundation process is therefore obtained by identifying image series. In addition to the spatial data, the water level evolutions at three gauges are also monitored to supply detailed hydrodynamic information at gauges. The repeatability of the experiments and reliability of the deep learning technique are verified. The experimental data including spatial and point hydrodynamic features for flood events can be used to systematically validate numerical model and calibrate parameters.