bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-existing immune status associated with response to combination of sipuleucel-T and ipilimumab in patients with metastatic castration-resistant prostate cancer
Authors: Sinha Meenal , Zhang Li , Subudhi Sumit , Chen Brandon , Marquez Jaqueline , Liu Eric V , Allaire Kate , Cheung Alexander , Ng Sharon , Nguyen Christopher , Friedlander Terence W , Aggarwal Rahul , Spitzer Matthew , Allison James P , Small Eric J , Sharma Padmanee , Fong Lawrence 
Published: May 2021

BackgroundSipuleucel-T is a US Food and Drug Administration-approved autologous cellular immunotherapy that improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We examined whether administering ipilimumab after sipuleucel-T could modify immune and/or clinical responses to this treatment.MethodsA total of 50 patients with mCRPC were enrolled into a clinical trial (NCT01804465, ClinicalTrials.gov) where they received ipilimumab either immediately or delayed 3 weeks following completion of sipuleucel-T treatment. Blood was collected at various timepoints of the study. Luminex assay for anti-prostatic acid phosphatase (PAP) and anti-PA2024-specific serum immunoglobulin G (IgG) and ELISpot for interferon-γ (IFN-γ) production against PAP and PA2024 were used to assess antigen-specific B and T cell responses, respectively. Clinical response was defined as >30% reduction in serum prostate-specific antigen levels compared with pretreatment levels. The frequency and state of circulating immune cells were determined by mass cytometry by time-of-flight and statistical scaffold analysis.ResultsWe found the combination to be well tolerated with no unexpected adverse events occurring. The timing of ipilimumab did not significantly alter the rates of antigen-specific B and T cell responses, the primary endpoint of the clinical trial. Clinical responses were observed in 6 of 50 patients, with 3 having responses lasting longer than 3 months. The timing of ipilimumab did not significantly associate with clinical response or toxicity. The combination treatment did induce CD4 and CD8 T cell activation that was most pronounced with the immediate schedule. Lower frequencies of CTLA-4 positive circulating T cells, even prior to treatment, were associated with better clinical outcomes. Interestingly, these differences in CTLA-4 expression were associated with prior localized radiation therapy (RT) to the prostate or prostatic fossa. Prior radiation treatment was also associated with improved radiographic progression-free survival.ConclusionCombining CTLA-4 blockade with sipuleucel-T resulted in modest clinical activity. The timing of CTLA-4 blockade following sipuleucel-T did not alter antigen-specific responses. Clinical responses were associated with both lower baseline frequencies of CTLA-4 expressing T cells and a history of RT. Prior cancer therapy may therefore result in long-lasting immune changes that influence responsiveness to immunotherapy with sipuleucel-T and anti-CTLA-4.
Pretreatment metastatic growth rate determines clinical outcome of advanced melanoma patients treated with anti-PD-1 antibodies: a multicenter cohort study
Authors: Wagner Nikolaus B , Lenders Max M , Kühl Kathrin , Reinhardt Lydia , André Fiona , Dudda Milena , Ring Natalie , Ebel Chiara , Stäger Ramon , Zellweger Caroline , Lang Roland , Paar Michael , Gussek Philipp , Richtig Georg , Stürmer Suzan H , Kimeswenger Susanne , Oellinger Angela , Forschner Andrea , Leiter Ulrike , Weide Benjamin , Gassenmaier Maximilian , Schraag Amadeus , Klumpp Bernhard , Hoetzenecker Wolfram , Berking Carola , Richtig Erika , Ziemer Mirjana , Mangana Johanna , Terheyden Patrick , Loquai Carmen , Nguyen Van Anh , Gebhardt Christoffer , Meier Friedegund , Diem Stefan , Cozzio Antonio , Flatz Lukas , Röcken Martin , Garbe Claus , Eigentler Thomas K 
Published: May 2021

BackgroundCheckpoint inhibitors revolutionized the treatment of metastatic melanoma patients. Although tumor burden and lactate dehydrogenase (LDH) are associated with overall survival (OS), the impact of tumor growth kinetics remains elusive and in part contradictory. The aims of this study were to develop a novel simple and rapid method that estimates pretreatment metastatic growth rate (MGR) and to investigate its prognostic impact in melanoma patients treated with antiprogrammed death receptor-1 (PD-1) antibodies.MethodsMGR was assessed in three independent cohorts of a total of 337 unselected consecutive metastasized stage IIIB–IV melanoma patients (discovery cohort: n=53, confirmation cohort: n=126, independent multicenter validation cohort: n=158). MGR was computed during the pretreatment period before initiation of therapy with anti-PD-1 antibodies nivolumab or pembrolizumab by measuring the increase of the longest diameter of the largest target lesion. Tumor doubling time served as quality control. Kaplan-Meier analysis and univariable as well as multivariable Cox regression were used to examine the prognostic impact of MGR.ResultsPretreatment MGR >3.9 mm/month was associated with impaired OS in the discovery cohort (HR 6.19, 95% CI 2.92 to 13.10, p<0.0001), in the confirmation cohort (HR 3.62, 95% CI 2.19 to 5.98, p<0.0001) and in the independent validation cohort (HR 2.57, 95% CI 1.56 to 4.25, p=0.00023). Prior lines of systemic treatment did not influence the significance of MGR. Importantly, the prognostic impact of MGR was independent of total tumor burden, diameter of the largest metastasis, number of prior lines of systemic treatment, LDH, as well as liver and brain metastasis (discovery and confirmation cohorts: both p<0.0001). Superiority of MGR compared with these variables was confirmed in the independent multicenter validation cohort (HR 2.92, 95% CI 1.62 to 5.26, p=0.00036).ConclusionsHigh pretreatment MGR is an independent strong prognostic biomarker associated with unfavorable survival of melanoma patients receiving anti-PD-1 antibodies. Further investigations are warranted to assess the predictive impact of MGR in distinct systemic therapeutic regimens.
Progression of cerebral infarction before and after thrombectomy is modified by prehospital pathways
Authors: Kollikowski Alexander M , Cattus Franziska , Haag Julia , Feick Jörn , März Alexander G , Weidner Franziska , Schuhmann Michael K , Müllges Wolfgang , Stoll Guido , Pham Mirko , Strinitz Marc 
Published: May 2021

BackgroundEvidence of the consequences of different prehospital pathways before mechanical thrombectomy (MT) in large vessel occlusion stroke is inconclusive. The aim of this study was to investigate the infarct extent and progression before and after MT in directly admitted (mothership) versus transferred (drip and ship) patients using the Alberta Stroke Program Early CT Score (ASPECTS).MethodsASPECTS of 535 consecutive large vessel occlusion stroke patients eligible for MT between 2015 to 2019 were retrospectively analyzed for differences in the extent of baseline, post-referral, and post-recanalization infarction between the mothership and drip and ship pathways. Time intervals and transport distances of both pathways were analyzed. Multiple linear regression was used to examine the association between infarct progression (baseline to post-recanalization ASPECTS decline), patient characteristics, and logistic key figures.ResultsASPECTS declined during transfer (9 (8–10) vs 7 (6-9), p<0.0001), resulting in lower ASPECTS at stroke center presentation (mothership 9 (7–10) vs drip and ship 7 (6–9), p<0.0001) and on follow-up imaging (mothership 7 (4–8) vs drip and ship 6 (3–7), p=0.001) compared with mothership patients. Infarct progression was significantly higher in transferred patients (points lost, mothership 2 (0–3) vs drip and ship 3 (2–6), p<0.0001). After multivariable adjustment, only interfacility transfer, preinterventional clinical stroke severity, the degree of angiographic recanalization, and the duration of the thrombectomy procedure remained predictors of infarct progression (R2=0.209, p<0.0001).ConclusionsInfarct progression and postinterventional infarct extent, as assessed by ASPECTS, varied between the drip and ship and mothership pathway, leading to more pronounced infarction in transferred patients. ASPECTS may serve as a radiological measure to monitor the benefit or harm of different prehospital pathways for MT.
Evaluation of a novel flow diverter, the DiVeRt system, in an animal model
Authors: Hufnagl Clemens , Broussalis Erasmia , Cognard Christophe , Grimm Jochen , Hecker Constantin , Oellerer Andreas , Abdallah Muhammed , Griessenauer Christoph J , Killer-Oberpfalzer Monika 
Published: May 2021

BackgroundUsing a surgical aneurysm model, this study assessed the performance of a new flow diverter (FD), the DiVeRt, and evaluated the angiographic and histologic features at different periods after stent deployment.MethodsFifteen New Zealand White rabbits were treated 3 days prior to intervention and until euthanization with dual antiplatelets. DiVeRt was implanted in bilateral carotid aneurysms (n=30) as well as in the aorta (n=15). The rate of technical success, assessment of aneurysm occlusion (measured by the O'Kelly–Marotta grading (OKM) scale), and stent patency were examined using angiography and histologic examinations in three groups at 1, 3, and 6 months follow-up (FU). In each FU group one control animal was included and treated with the XCalibur stent (n=3).ResultsOverall, DiVeRt placement was successful and without apparent intraprocedural complications. In total, four stents in the carotid artery were occluded and in-stent stenosis was registered in two carotid (7%) and one aortic (6%) vessels. Complete or near complete aneurysm occlusion (OKM scale D1 and C3) was seen in 100% in the 1-month FU group, 70% in the 2-month FU group, and 100% in the 3-month FU group. Histology showed loose, organizing fibrous tissue matrix within the sac and adequate neck endothelialization in all vessels. All branches covered by the DiVeRt remained patent.ConclusionsThe DiVeRt system appears to be feasible and effective for the treatment of aneurysms with high rates of complete aneurysm occlusion, excellent vessel patency, and evidence of high biocompatibility. Occurrences of parent artery occlusion at follow-up did not result in clinical consequences.
Early recanalization in large-vessel occlusion stroke patients transferred for endovascular treatment
Authors: Arrarte Terreros Nerea , Bruggeman Agnetha A E , Swijnenburg Isabella S J , van Meenen Laura C C , Groot Adrien E , Coutinho Jonathan M , Roos Yvo B W E M , Emmer Bart J , Beenen Ludo F M , van Bavel Ed , Marquering Henk A , Majoie Charles B L M 
Published: May 2021

BackgroundWe performed an exploratory analysis to identify patient and thrombus characteristics associated with early recanalization in large-vessel occlusion (LVO) stroke patients transferred for endovascular treatment (EVT) from a primary (PSC) to a comprehensive stroke center (CSC).MethodsWe included patients with an LVO stroke of the anterior circulation who were transferred to our hospital for EVT and underwent repeated imaging between January 2016 and June 2019. We compared patient characteristics, workflow time metrics, functional outcome (modified Rankin Scale at 90 days), and baseline thrombus imaging characteristics, which included: occlusion location, thrombus length, attenuation, perviousness, distance from terminus of intracranial carotid artery to the thrombus (DT), and clot burden score (CBS), between early-recanalized LVO (ER-LVO), and non-early-recanalized LVO (NER-LVO) patients.ResultsOne hundred and forty-nine patients were included in the analysis. Early recanalization occurred in 32% of patients. ER-LVO patients less often had a medical history of hypertension (31% vs 49%, P=0.04), and more often had clinical improvement between PSC and CSC (ΔNIHSS −5 vs 3, P<0.01), compared with NER-LVO patients. Thrombolysis administration was similar in both groups (88% vs 78%, P=0.18). ER-LVO patients had no ICA occlusions (0% vs 27%, P<0.01), more often an M2 occlusion (35% vs 17%, P=0.01), longer DT (27 mm vs 12 mm, P<0.01), shorter thrombi (17 mm vs 27 mm, P<0.01), and higher CBS (8 vs 6, P<0.01) at baseline imaging. ER-LVO patients had lower mRS scores (1 vs 3, P=0.02).ConclusionsEarly recanalization is associated with clinical improvement between PSC and CSC admission, more distal occlusions and shorter thrombi at baseline imaging, and better functional outcome.
Evidence of eutrophication in Arctic lakes
Authors: Ayala-Borda Paola , Lovejoy Connie , Power Michael , Rautio Milla 
Published: May 2021

Lakes and ponds are dominant components of Arctic landscapes and provide food and water for northern communities. In the Greiner Lake watershed, in Cambridge Bay (Nunavut, Canada), water bodies are small (84% <5 ha) and shallow (99% <4 m deep). Such characteristics make them vulnerable to eutrophication as temperatures rise and nutrient concentrations from the greening landscape increase. Here, we investigated and compared 35 lakes and ponds in the Greiner watershed in August 2018 and 2019 to determine their current trophic states based on their chemical composition and phytoplankton communities. The ponds had higher trophic status than the lakes, but overall, most sites were oligotrophic. Lake ERA5, located upstream of any direct human influence was classified as eutrophic due to high total phosphorus (32.3 μg·L−1) and a high proportion of Cyanobacteria (42.9% of total phytoplankton biovolume). Satellite imagery suggests the lake may have been eutrophic for the last 30 years. We hypothesize that the coupled effects of catchment characteristics and elevated local snow accumulation patterns promote higher nutrient leaching rates from the soils. We recommend further analysis and monitoring as eutrophication could become more widespread with ongoing climate change and the associated increases in temperature, precipitation, and catchment–lake coupling.
Semantic Table Retrieval Using Keyword and Table Queries
Authors: Zhang Shuo , Balog Krisztian 
Published: May 2021

Tables on the Web contain a vast amount of knowledge in a structured form. To tap into this valuable resource, we address the problem of table retrieval: answering an information need with a ranked list of tables. We investigate this problem in two different variants, based on how the information need is expressed: as a keyword query or as an existing table (“query-by-table”). The main novel contribution of this work is a semantic table retrieval framework for matching information needs (keyword or table queries) against tables. Specifically, we (i) represent queries and tables in multiple semantic spaces (both discrete sparse and continuous dense vector representations) and (ii) introduce various similarity measures for matching those semantic representations. We consider all possible combinations of semantic representations and similarity measures and use these as features in a supervised learning model. Using two purpose-built test collections based on Wikipedia tables, we demonstrate significant and substantial improvements over state-of-the-art baselines.
Access to Mechanical Thrombectomy for Ischemic Stroke in the United States
Authors: Kamel Hooman , Parikh Neal S. , Chatterjee Abhinaba , Kim Luke K. , Saver Jeffrey L. , Schwamm Lee H. , Zachrison Kori S. , Nogueira Raul G. , Adeoye Opeolu , Díaz Iván , Ryan Andrew M. , Pandya Ankur , Navi Babak B. 
Published: May 2021

Background and Purpose:
Mechanical thrombectomy helps prevent disability in patients with acute ischemic stroke involving occlusion of a large cerebral vessel. Thrombectomy requires procedural expertise and not all hospitals have the staff to perform this intervention. Few population-wide data exist regarding access to mechanical thrombectomy.

Methods:
We examined access to thrombectomy for ischemic stroke using discharge data from calendar years 2016 to 2018 from all nonfederal emergency departments and acute care hospitals across 11 US states encompassing 80 million residents. Facilities were classified as hubs if they performed mechanical thrombectomy, gateways if they transferred patients who ultimately underwent mechanical thrombectomy, and gaps otherwise. We used standard descriptive statistics and unadjusted logistic regression models in our primary analyses.

Results:
Among 205 681 patients with ischemic stroke, 100 139 (48.7% [95% CI, 48.5%–48.9%]) initially received care at a thrombectomy hub, 72 534 (35.3% [95% CI, 35.1%–35.5%]) at a thrombectomy gateway, and 33 008 (16.0% [95% CI, 15.9%–16.2%]) at a thrombectomy gap. Patients who initially received care at thrombectomy gateways were substantially less likely to ultimately undergo thrombectomy than patients who initially received care at thrombectomy hubs (odds ratio, 0.27 [95% CI, 0.25–0.28]). Rural patients had particularly limited access: 27.7% (95% CI, 26.9%–28.6%) of such patients initially received care at hubs versus 69.5% (95% CI, 69.1%–69.9%) of urban patients. For 93.8% (95% CI, 93.6%–94.0%) of patients with stroke at gateways, their initial facility was capable of delivering intravenous thrombolysis, compared with 76.3% (95% CI, 75.8%–76.7%) of patients at gaps. Our findings were unchanged in models adjusted for demographics and comorbidities and persisted across multiple sensitivity analyses, including analyses adjusting for estimated stroke severity.

Conclusions:
We found that a substantial proportion of patients with ischemic stroke across the United States lacked access to thrombectomy even after accounting for interhospital transfers. US systems of stroke care require further development to optimize thrombectomy access.
Tradition, Habitat and Well-Being
Authors: Li Zhi-nong , He Shu-qing 
Published: May 2021

Abstract
The Tibetans who live among the valleys and mountains of the Jinsha River region, on the southeastern edge of the Qinghai–Tibet Plateau, still retain a considerable number of polygamous marriages. Through fieldwork in a Tibetan village, the authors discovered that polygamous marriage is a rational choice compatible with Tibetans’ traditional culture and natural environment, which can improve family well-being and lead to a good life. Our findings provide new fieldwork materials to support theories of cultural relativism advocated by the Boas school, which emphasises that the environment greatly affects culture, and Malinowski’s functionalism, which stresses that culture has been created to satisfy people’s practical needs.
Public Acceptance of Water Reuse for Agriculture in the Wake of the New EU Regulation: Early Reflections
Authors: Berti Suman Anna , Toscano Attilio 
Published: May 2021

Abstract
Domestic wastewater reuse in agriculture is often discussed as a way to tackle water scarcity in Europe. Europe could learn from the examples of other countries that are already successfully implementing wastewater reuse, especially in the Mediterranean. However, the potential of the practice is currently unfulfilled mainly due to social and legal barriers, including public resistance and the lack of a unified legislative framework at the European Union (EU) level. In the wake of the new EU Water Reuse Regulation released in June 2020, we wonder how this legislative intervention can foster public acceptance of non-conventional water reuse practices in agriculture. The original contribution of this piece is to provide a novel discussion of the transformations potentially triggered by the new EU Regulation and to suggest an innovative way forward, based on engaging interested users in water quality monitoring (i.e. water citizen science). We combine theoretical and empirical analysis, grounding our findings in an overarching theoretical concept, i.e. the neo-institutionalism theory. We conclude that the main catalysts for stimulating public acceptance can be identified in a unifying legislative tool represented by the recent EU Regulation and in the promotion of participatory water monitoring initiatives, also in line with the spirit of the EU Regulation.
The European Court of Human Rights and Domestic Violence: Volodina v. Russia
Authors: McQuigg Ronagh J.A. 
Published: May 2021

Abstract
This article addresses the highly significant area of the approach adopted by the European Court of Human Rights (ECtHR) to the issue of domestic violence. During the past thirteen years, the Court has firmly established that domestic violence can constitute a violation of the European Convention on Human Rights (echr), however the way in which this issue has been contextualised by the ECtHR has varied and evolved, namely in terms of which articles of the echr have been held to have been violated in such cases. The Court’s recent judgment in Volodina v Russia again raises important questions regarding the conceptualisation of domestic violence by the ECtHR, as discussed in this article.
A forum for the discussion of issues in zoological taxonomy
Authors: ZHANG ZHI-QIANG 
Published: May 2021

Zootaxa was founded in 2001 to help systematists rapidly document the World’s zoological diversity, which includes many undescribed species now threatened by the rapid habitat loss (Zhang 2006). The journal was initially published as a monographic series—each paper or monograph was separately titled, issued and published. Because of the lower limit of four pages for a book or journal issue, manuscripts less than four pages were not published, including short items such as errata that should normally be published.
Structure and Dynamics of Ensemble Correlations for Satellite All-Sky Observations in an FV3-Based Global-to-Regional Nested Convection-Permitting Ensemble Forecast of Hurricane Harvey
Authors: Zhang Yunji , Chen Xingchao , Lu Yinghui 
Published: May 2021

AbstractThere are ongoing efforts to establish an ensemble data assimilation and prediction system for tropical cyclones based on the FV3 (finite-volume cubed-sphere) dynamic core with the capability to assimilate satellite all-sky infrared and microwave observations. To complement the system developments and improve our understanding of the assimilation of all-sky infrared and microwave observations, this study assesses their potential impacts on the analysis of Hurricane Harvey (2017) through examinations of the structure and dynamics of the ensemble-based correlations as well as single observation data assimilation experiments, using an ensemble forecast generated by a global-to-regional nested FV3-based model. It is found that different infrared and microwave channels are sensitive to different types of hydrometeors within different layers of the atmosphere, and the correlations vanish beyond 200 km in the region covered by cloud or abundant hydrometeors. The spatial correlations between brightness temperatures and model states will adjust the structure and intensity of the hurricane in the model so that the simulated hurricane will better fit the “observed” brightness temperatures. In general, these results show how assimilating infrared and microwave together can improve the analyses of tropical cyclone intensity and structure, which may lead to improved intensity forecasts.