bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative donor
Authors: Foell Juergen , Kleinschmidt Katharina , Jakob Marcus , Troeger Anja , Corbacioglu Selim 
Published: March 2020

Sickle cell disease (SCD) is an inherited disorder; despite significant improvements in supportive care, SCD continues to cause substantial morbidity, mortality, and reduced life expectancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only widely available curative therapy for SCD, which is offered as a standard of care for patients with a matched sibling donor (MSD). Donor availability is limited to a minority of patients. Thus, ab/CD3-depleted haploidentical HSCT, as an efficient means for depletion of graft-versushost disease (GvHD)-mediating T cells, can be offered as an alternative curative therapy, particularly for nonmalignant diseases such as SCD.
Out of 38 patients with advanced stage SCD, 25 were transplanted with CD3/CD19-or T-cell receptor αβ/CD19 T-cell-depleted peripheral stem cell grafts (T-haplo-HSCT group), whereas 13 transplanted from MSD (MSD group); both groups received an almost identical conditioning regimen. Engraftment was achieved in all. However, in the T-haplo-HSCT group, three patients succumbed to an uncontrolled cytomegalovirus pneumonitis, a macrophage activation syndrome, and a major blood group incompatibility with a late graft failure and multiorgan failure. The overall survival was 88% and 100% in T-haplo-HSCT and MSD groups, respectively. None of our patients developed a Glucksberg Grade III-IV acute GvHD. Four patients (16%) in the T-haplo-HSCT group and two patients (15%) in the MSD group developed a steroid-sensitive, mild-to-moderate chronic GvHD that resolved within 18 months posttransplant.
These results are encouraging and demonstrate the feasibility, safety, and efficacy of T-haplo-HSCT in advanced stage SCD in children and adults, thus offering a curative alternative to majority of patients.
Wilderness Medicine Simulation-Based Teaching Program for Medical Students in the UK
Authors: To Benjaman , Tailor Bhavesh V. , Beverley Jodie , Moore George , Peng Yuhan 
Published: March 2020

Introduction The UK undergraduate medicine curriculum provides insufficient opportunities for medical students to explore the field of wilderness medicine, despite interest in the area. The student-led Cambridge University Wilderness Medicine Society devised a low-cost wilderness medicine teaching weekend that can be replicated at other institutions. Methods The weekend course consisted of small-group lessons introducing the roles of the expedition doctor and expedition leader and the assessment and management of acute conditions in remote environments. This was followed by a 3-station circuit to teach the principles of casualty triage, splinting, and construction of rope stretchers. These skills were then practiced in simulations in which participants rotated roles as care providers and patients. Participant confidence was compared before the course and immediately on course completion using the related-samples Wilcoxon signed-ranks test with significance accepted at P<0.05. Usefulness of course content and perceptions of learning were also assessed. Results Sixty-one medical students attended the wilderness teaching weekend and completed the structured feedback questionnaires. Participants rated the course highly in terms of usefulness of course content (mean±SD=18.3±1.9, range=12–20) and perceptions of learning (mean±SD=37.6±2.6, range=31–40), with 92% of participants “strongly agreeing” that the course was of high quality. There was an improvement in perceived confidence after course completion ( P<0.001). Conclusions We have demonstrated that a teaching program consisting of structured, low-cost “teaching weekends” is a potential solution to the lack of centralized national wilderness medicine teaching and can be integrated, with minimal disruption, into the undergraduate curriculum.
Sinonasal cancer: an overview of the emerging subtypes
Authors: Virk J S , Chan J , Dimitrov L , Williamson A , Sandison A , Weir J , Clarke P 
Published: March 2020

AbstractBackgroundAdvances in immunohistochemistry have spearheaded major developments in our understanding and classification of sinonasal tumours. In the last decade, several new distinct histopathological entities of sinonasal cancer have been characterised.ObjectivesThis review aims to provide a clinical update of the major emerging subtypes for the ENT surgeon and an overview of the management strategies available for this heterogeneous group of pathologies.ConclusionAlthough rare, knowledge of sinonasal neoplasm subtypes has implications for prognosis, treatment strategies and the development of novel therapeutic targets.
Once more to the hotel
Authors: HEDRICK LANDON 
Published: March 2020

AbstractWilliam Lane Craig's defence of the so-called ‘Hilbert's Hotel Argument’ for the beginning of the universe seems to be in conflict with his own presentist views, as I argued in my earlier article ‘Heartbreak at Hilbert's Hotel’ (2014). In response, Andrew Loke (2014) has defended a modified version of the argument which avoids this problem, and this defence has been endorsed by Craig (2018). After clarifying the dialectic, I argue in this article that Loke's modification is not as straightforwardly successful as he and Craig seem to think, and that it in fact requires a controversial independent assumption – namely, that creation ex nihilo is possible. I show that some of the more obvious ways of supporting this assumption are either unsuccessful or unavailable to the proponent of the Hilbert's Hotel Argument. Moreover, I show that accepting this assumption conflicts with a key premise in the Hilbert's Hotel Argument. Hence, Loke's modified argument has not successfully established that the universe – including time itself – began to exist.
Prevalence and characteristics of pks gene cluster harbouring Klebsiella pneumoniae from bloodstream infection in China
Authors: Shi Qiucheng , Quan Jingjing , Lan Peng , Huang Danyan , Zhou Jiancang , Jiang Yan , Yu Yunsong 
Published: March 2020

Abstract
Bloodstream infection (BSI), caused by Klebsiella pneumoniae, is associated with high morbidity and mortality, where the pks gene cluster plays a major role in their occurrence and prevalence. Information on the prevalence and characteristics of this gene cluster in K. pneumoniae is currently limited in mainland China. We therefore undertook a multicentre longitudinal study which revealed the prevalence, overall, community-onset and hospital-acquired BSI to be 20.5%, 28.3% and 13.0%, respectively. Compared to pks-negative, pks-positive isolates were significantly more susceptible to antimicrobial agents with a low incidence (5.1%) of multidrug-resistance and with infrequent extended-spectrum beta-lactamase (ESBL) production. Among pks-positive isolates, ST23 (78/117) and ST65 (20/117) were the dominant sequence types, and the majority harboured virulence genes. Community-onset BSI patients infected with pks-positive isolates had a higher proportion of liver abscesses and a lower proportion of biliary obstructions (P < 0.05). The pks-positive isolates were mostly sporadic in the phylogenetic tree, with a 65.8 and 47.0 average allele difference between Clade 1 and Clade 2, respectively. We concluded that although pks-positive K. pneumoniae were generally susceptible to antimicrobials, the high prevalence of such isolates in community cases and the genotoxicity, merits further investigation.
Exploring the neglected dimension of the economic vote: a global analysis of the positional economics thesis
Authors: Quinlan Stephen , Okolikj Martin 
Published: March 2020

AbstractWhile much ink has been spilled as to how economics impacts election outcomes, existing scholarship has concentrated on the valence model, which focuses on assessments of incumbent administration’s handling of the economy. Recently, however, there has been an appreciation that economic voting is multidimensional. Nonetheless, the impact of positional economics – voters’ views of economic policy – on the vote remains less explored, especially from a cross-national perspective. In this contribution, we examine the impact of economic policy preferences regarding income redistribution and spending preferences on the vote in 32 states. Using the Comparative Study of Electoral Systems Module 4 data and hierarchical models, we show that voters’ economic policy preferences directly impact vote choice in many states. We also show that positional economic voting is more likely to take hold in mature democracies. However, support for the idea that ideological polarization contributes to macro-diversity concerning positional economic voting is mixed at best. Our research breaks new ground regarding positional economic voting and highlights how context impacts the extent of positional economic voting.
Use of Double Channel Differences for Reducing the Surface Emissivity Dependence of Microwave Atmospheric Temperature and Humidity Retrievals
Authors: Cui X. , Yao Z. , Zhao Z. , Zhai Y. , Sun Z. , Cheng W. , Gu C. 
Published: March 2020

AbstractSurface emissivity has a significant impact on atmospheric parameter retrievals from microwave sounding instruments. To reduce the dependence of retrievals on surface emissivity, a double channel differences equation is deduced, and a corresponding retrieval scheme is constructed. Retrieval experiments are performed using Advanced Microwave Sounding Unit‐A (AMSU‐A) and Microwave Humidity Sounder (MHS) simulations and global measurements. Simulation experiments show that the double channel differences scheme can reduce the root mean square errors (RMSE) of the temperature and humidity profiles in the middle and lower atmosphere. Retrieval experiments based on AMSU‐A and MHS global measurements show that the proposed scheme can significantly reduce the RMSE of temperature profiles in the lower atmosphere and humidity profiles in the middle and lower atmosphere for cloudy and cloudless conditions, different surface types, and different scan angles, with maximum reduction values of 0.64 K and 9.03%, respectively. Regarding RMSE improvement, that of the cloudy condition is greater than that of the cloudless condition, that of the land is greater than that of the coast and the sea, and there is no significant dependence on the scan angles. The double channel differences scheme is very sensitive to initial near‐surface temperatures. Reducing the initial near‐surface temperature error can significantly improve the temperature retrieval accuracy below 900 hPa, with maximum reduction value of 3.25 K.
Dynamic Rupture Simulations of theM6.4 andM7.1 July 2019 Ridgecrest, California, Earthquakes
Authors: Lozos J. C. , Harris R. A. 
Published: March 2020

AbstractThe largest earthquakes of the 2019 Ridgecrest, California, sequence were aM6.4 left‐lateral rupture followed 34 hr later by aM7.1 on a perpendicular right‐lateral fault. We use dynamic rupture modeling to address the questions of why the first earthquake did not propagate through the right‐lateral fault in one larger event, whether stress changes from theM6.4 were necessary for theM7.1 to occur, and how the Ridgecrest earthquakes affected the nearby Garlock Fault. We find that dynamic clamping and shear stress reduction confined surface rupture in theM6.4 to the left‐lateral fault. We also find that stress changes from theM6.4 were not necessary to allow aM7.1 on the right‐lateral fault but that they affected the slip and likely accelerated the timing of theM7.1. Lastly, we find that the Ridgecrest earthquakes may have brought the central Garlock Fault closer to failure.
A Polar Surface Eddy Obscured by Thermal Stratification
Authors: Porter M. , Henley S. F. , Orkney A. , Bouman H. A. , Hwang B. , Dumont E. , Venables E. J. , Cottier F. 
Published: March 2020

AbstractMesoscale and submesoscale eddies play an important role in the distribution of heat and biogeochemical properties throughout the global oceans. Such eddies are important in the Arctic Ocean, particularly in the frontal regions, but are difficult to detect using traditional satellite‐based methods. Here we use high‐resolution in situ data from an underwater glider to identify a surface eddy that was masked from remote‐sensing observations. We hypothesize that this masking was driven by thermal stratification driven by surface heat fluxes. The eddy was likely generated north of the Polar Front, before crossing the front and traveling south. We estimate that the observed eddy contained 4 × 1010 m3 of Arctic Water. The observation of this eddy, masked in satellite observations of sea surface temperature, suggests a historical underestimation of the prevalence and importance of eddies in this key mixing region. The water column of the Barents Sea, one of the circumpolar Arctic seas has a seemingly simple structure. In the south, warm Atlantic Water dominates; in the north, cold Arctic Water dominates; while at their boundary, the Arctic Water overlies the Atlantic Water. In the summer, the Arctic Water is largely devoid of the nutrients required to fuel the growth of phytoplankton, which is key to maintaining life in the ocean. In contrast, the Atlantic Water is one of the primary sources of nutrient‐rich water into the Arctic. In this study, we have used an underwater robotic instrument to identify a patch of Arctic Water which has been shed from the Arctic sector of the Barents Sea into the Atlantic sector. This patch of water is seen to have lower phytoplankton concentrations than the surrounding water. Due to atmospheric heating of the surface, this patch would be indistinguishable from the surrounding Atlantic Water and so would be absent for satellite observations of sea surface temperature. We suggest that this temperature masking has meant that we have previously underestimated how much water is moved within these patches in the Arctic seas.
Channel Network Control on Seasonal Lake Area Dynamics in Arctic Deltas
Authors: Vulis Lawrence , Tejedor Alejandro , Schwenk Jon , Piliouras Anastasia , Rowland Joel , Foufoula‐Georgiou Efi 
Published: March 2020

AbstractThe abundant lakes dotting arctic deltas are hotspots of methane emissions and biogeochemical activity, but seasonal variability in lake extents introduces uncertainty in estimates of lacustrine carbon emissions, typically performed at annual or longer time scales. To characterize variability in lake extents, we analyzed summertime lake area loss (i.e., shrinkage) on two deltas over the past 20 years, using Landsat‐derived water masks. We find that monthly shrinkage rates have a pronounced structured variability around the channel network with the shrinkage rate systematically decreasing farther away from the channels. This pattern of shrinkage is predominantly attributed to a deeper active layer enhancing near‐surface connectivity and storage and greater vegetation density closer to the channels leading to increased evapotranspiration rates. This shrinkage signal, easily extracted from remote sensing observations, may offer the means to constrain estimates of lacustrine methane emissions and to develop process‐based estimates of depth to permafrost on arctic deltas.
Observed Warm‐Season Characteristics of MCS and Non‐MCS Rainfall and Their Recent Changes in the Central United States
Authors: Hu Huancui , Leung L. Ruby , Feng Zhe 
Published: March 2020

AbstractWarm‐season rainfall characteristics in the central United States are investigated as they play important roles in ecohydrology and agricultural productivity. Using rainfall observations, we compare the April–August mesoscale convective systems (MCS) and non‐MCS rainfall characteristics and examine their linear trends between 1997 and 2018. MCS rainfall is found to be approximately seven times more intense than non‐MCS rainfall but it occurs less frequently in time and space. MCS rainfall peaks in nocturnal hours, with synchronized timing of rainfall intensity, area, and occurrence, while non‐MCS rainfall peaks in late‐afternoon hours, mostly attributed to the timing of peak rainfall area. MCS rainfall has increased in the last 22 years due to an increase in frequency and a longer duration per MCS. In contrast, non‐MCS rainfall has decreased mainly due to a reduction in rainfall area, leading to fewer total wet days and increased dry intervals between events.
Assessing Compound Flooding From Landfalling Tropical Cyclones on the North Carolina Coast
Authors: Gori Avantika , Lin Ning , Smith James 
Published: March 2020

AbstractTropical cyclone (TC) events are major drivers of compound flooding due to the interaction of wind‐driven storm surge and TC rainfall. Traditionally, coastal flood risk models have only taken into account surge flooding, even though it is known that the role of rainfall‐runoff is critical. There is limited understanding about the types of TC events that are capable of producing significant compounding and how site conditions at the coast affect the extent to which storm surge and rainfall‐runoff interact. This study investigates a suite of historical TCs making landfall near the Cape Fear River Estuary, NC, through a loosely coupled physical modeling methodology in order to draw conclusions about the spatial and temporal patterns of storm surge and rainfall that are able to induce significant compound impacts. Results indicate that intense outer rain bands falling over inland portions of the study area can be a driver of river‐surge compounding (increasing river levels by up to 0.36 m), while intense eyewall rainfall along the coast can result in localized compound impacts to coastal streams and tributaries if peak rainfall occurs near the time of peak storm tide. These localized compound impacts can result in defined interaction zones, where neither storm tide alone nor rainfall‐runoff alone can fully explain the observed maximum water levels. These results provide insight about the relative timing and spatial patterns of rainfall and storm surge that are capable of inducing compound flooding during TC events.
Spatially Distinct Effects of Two El Niño Types on Summer Heat Extremes in China
Authors: Gao Tao , Luo Ming , Lau Ngar‐Cheung , Chan Ting On 
Published: March 2020

AbstractChanges in the activity of summer high‐temperature extremes (HTEs) over many regions are linked with the El Niño‐Southern Oscillation. However, how the HTEs respond to different flavors of El Niño remains unclear. Using observational analyses, we show that summer HTEs in China during eastern Pacific (EP) and central Pacific (CP) types of El Niño exhibit different spatial patterns. EP (CP) El Niño is significantly correlated with summer HTEs over South China (Yangtze River valley). These relationships can be attributed to the modulation of the western North Pacific subtropical high and the East Asian jet stream. EP (CP) El Niño events are accompanied by westward (eastward) extension of the western North Pacific subtropical high and equatorward (poleward) movement of the jet stream over East Asia (Pacific). During EP (CP) El Niño episodes, the westward (eastward) and equatorward (poleward) displacements of upper‐tropospheric anticyclone over the western North Pacific coincide with the subsidence anomaly over South China (Yangtze River valley).
Detection of Negative Pickup Ions at Saturn's Moon Dione
Authors: Nordheim T. A. , Wellbrock A. , Jones G. H. , Desai R. T. , Coates A. J. , Teolis B. D. , Jasinski J. M. 
Published: March 2020

AbstractWe investigate a possible negative ion feature observed by the Cassini Plasma Spectrometer (CAPS) during a flyby of Saturn's moon Dione that occurred on 7 April 2010. By examining possible particle trajectories, we find that the observed particles are consistent with negative pickup ions originating near the moon's surface. We find that the mass of the negative pickup ions is in the range of 15–25 u and tentatively identify this species as O−, likely resulting from ionization and subsequent pickup from Dione's O2‐CO2 exosphere. Our estimates show that the negative ion density is ~3 × 10−3 cm−3. This is comparable to, but slightly smaller than, that previously reported for the density of O2+ pickup ions for the same flyby, indicating that negative pickup ions may represent a major loss channel for Dione's exosphere.
Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours
Authors: de Bono Johann , Lin Chia-Chi , Chen Li-Tzong , Corral Jesus , Michalarea Vasiliki , Rihawi Karim , Ong Michael , Lee Jih-Hsiang , Hsu Chih-Hung , Yang James Chih-Hsin , Shiah Her-Shyong , Yen Chia-Jui , Anthoney Alan , Jove Maria , Buschke Susanne , Fuertig René , Schmid Ulrike , Goeldner Rainer-Georg , Strelkowa Natalja , Huang Dennis Chin-Lun , Bogenrieder Thomas , Twelves Chris , Cheng Ann-Lii 
Published: March 2020

Abstract
Background
Xentuzumab, an insulin-like growth factor (IGF)-1/IGF-2-neutralising antibody, binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling. Two first-in-human trials assessed the maximum-tolerated/relevant biological dose (MTD/RBD), safety, pharmacokinetics, pharmacodynamics, and activity of xentuzumab in advanced/metastatic solid cancers.

Methods
These phase 1, open-label trials comprised dose-finding (part I; 3 + 3 design) and expansion cohorts (part II; selected tumours; RBD [weekly dosing]). Primary endpoints were MTD/RBD.

Results
Study 1280.1 involved 61 patients (part I: xentuzumab 10–1800 mg weekly, n = 48; part II: 1000 mg weekly, n = 13); study 1280.2, 64 patients (part I: 10–3600 mg three-weekly, n = 33; part II: 1000 mg weekly, n = 31). One dose-limiting toxicity occurred; the MTD was not reached for either schedule. Adverse events were generally grade 1/2, mostly gastrointestinal. Xentuzumab showed dose-proportional pharmacokinetics. Total plasma IGF-1 increased dose dependently, plateauing at ~1000 mg/week; at ≥450 mg/week, IGF bioactivity was almost undetectable. Two partial responses occurred (poorly differentiated nasopharyngeal carcinoma and peripheral primitive neuroectodermal tumour). Integration of biomarker and response data by Bayesian Logistic Regression Modeling (BLRM) confirmed the RBD.

Conclusions
Xentuzumab was well tolerated; MTD was not reached. RBD was 1000 mg weekly, confirmed by BLRM. Xentuzumab showed preliminary anti-tumour activity.

Clinical trial registration
NCT01403974; NCT01317420.
A supertough electro-tendon based on spider silk composites
Authors: Pan Liang , Wang Fan , Cheng Yuan , Leow Wan Ru , Zhang Yong-Wei , Wang Ming , Cai Pingqiang , Ji Baohua , Li Dechang , Chen Xiaodong 
Published: March 2020

AbstractCompared to transmission systems based on shafts and gears, tendon-driven systems offer a simpler and more dexterous way to transmit actuation force in robotic hands. However, current tendon fibers have low toughness and suffer from large friction, limiting the further development of tendon-driven robotic hands. Here, we report a super tough electro-tendon based on spider silk which has a toughness of 420 MJ/m3and conductivity of 1,077 S/cm. The electro-tendon, mechanically toughened by single-wall carbon nanotubes (SWCNTs) and electrically enhanced by PEDOT:PSS, can withstand more than 40,000 bending-stretching cycles without changes in conductivity. Because the electro-tendon can simultaneously transmit signals and force from the sensing and actuating systems, we use it to replace the single functional tendon in humanoid robotic hand to perform grasping functions without additional wiring and circuit components. This material is expected to pave the way for the development of robots and various applications in advanced manufacturing and engineering.