bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunological response in cynomolgus macaques to porcine α‐1,3 galactosyltransferase knockout viable skin xenotransplants—A pre‐clinical study
Authors: Holzer Paul W. , Chang Elizabeth , Wicks Joan , Scobie Linda , Crossan Claire , Monroy Rod 
Published: August 2020

AbstractBackgroundAllogeneic skin recovered from human deceased donors (HDD) has been a mainstay interim treatment for severe burns, but unfortunately risk of infectious disease and availability limitations exist. Genetically engineered ɑ‐1,3 galactosyltransferase knockout (GalT‐KO) porcine source animals for viable skin xenotransplants may provide a promising clinical alternative.MethodsFour cynomolgus macaque recipients received full‐thickness surgical wounds to model the defects arising from excision of full‐thickness burn injury and were treated with biologically active skin xenotransplants derived from GalT‐KO, Designated Pathogen Free (DPF) miniature swine. Evaluations were conducted for safety, tolerability, and recipient immunological response.ResultsAll skin xenotransplants demonstrated prolonged survival, vascularity, and persistent dermal adhesion until the study endpoint at post‐operative day 30. No adverse outcomes were observed during the study. Varying levels of epidermolysis coincided with histologic detection of CD4+ and CD8+ T cells, and other cellular infiltrates in the epidermis. Recipient sera IgM and IgG demonstrated significant antibody immune response to non‐α‐1,3‐galactose porcine xenoantigens. Separately, specific wound healing mediators were quantified. Neither porcine cell migration nor PERV were detected in circulation or any visceral organs.ConclusionsThese results provide a detailed analysis of vital skin xenotransplants utilizing a non‐human primate model to predict the anticipated immunological response of human patients. The lack of adverse rejection even in the presence of elevated Ig indicates this is a prospective therapeutic option. The findings reported here directly supported regulatory clearance for a first‐in‐man, Phase I xenotransplantation clinical trial.
Architecture and function of NMDA receptors: an evolutionary perspective
Authors: Stroebel David , Paoletti Pierre 
Published: August 2020

AbstractIonotropic glutamate receptors (iGluRs) are a major class of ligand‐gated ion channels that are widespread in the living kingdom. Their critical role in excitatory neurotransmission and brain function of arthropods and vertebrates has made them a compelling subject of interest for neurophysiologists and pharmacologists. This is particularly true for NMDA receptor (NMDARs), a subclass of iGluRs that act as central drivers of synaptic plasticity in the CNS. How and when the unique properties of NMDARs arose during evolution, and how they relate to the evolution of the nervous system, remain open questions. Recent years have witnessed a boom in both genomic and structural data, such that it is now possible to analyse the evolution of iGluR genes on an unprecedented scale and within a solid molecular framework. In this review, combining insights from phylogeny, atomic structure and physiological and mechanistic data, we discuss how evolution of NMDAR motifs and sequences shaped their architecture and functionalities. We trace differences and commonalities between NMDARs and other iGluRs, emphasizing a few distinctive properties of the former regarding ligand binding and gating, permeation, allosteric modulation and intracellular signalling. Finally, we speculate on how specific molecular properties of iGuRs arose to supply new functions to the evolving structure of the nervous system, from early metazoan to present mammals.
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Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren's syndrome, regardless of dacryoadenitis status
Authors: Ohno Yuta , Satoh Keitaro , Shitara Akiko , Into Takeshi , Kashimata Masanori 
Published: August 2020

Key points
Few reports have explored the possibility of involvement of non‐inflammatory factors in lacrimal hyposecretion in Sjögren's syndrome (SS).
RNA‐sequencing analysis revealed that only four genes, including arginase 1, were downregulated in the lacrimal gland of SS model male mice (NOD mice) after onset of lacrimal hyposecretion and dacryoadenitis.
Even in non‐dacryoadenitis‐type NOD mice, tear secretion and arginase 1 expression remained low.
An arginase 1 inhibitor reduced tear secretion and partially reduced saliva secretion in BALB/c mice.
The results indicate that a non‐inflammatory factor, arginase 1, is involved in lacrimal hyposecretion in male NOD mice, regardless of dacryoadenitis status.
AbstractLacrimal fluid (tears) is important for preservation of the ocular surface, and thus lacrimal hyposecretion in Sjögren's syndrome (SS) leads to reduced quality of life. However, the cause(s) of lacrimal hyposecretion remains unknown, even though many studies have been conducted from the perspective of inflammation. Here, we hypothesized that a non‐inflammatory factor induces lacrimal hyposecretion in SS pathology, and to elucidate such a factor, we conducted transcriptome analysis of the lacrimal glands in male non‐obese diabetic (NOD) mice as an SS model. The NOD mice showed inflammatory cell infiltration and decreased pilocarpine‐induced tear secretion at and after 6 weeks of age compared to age‐matched BALB/c mice. RNA‐sequencing analysis revealed that only four genes, including arginase 1, were downregulated, whereas many genes relating to inflammation were upregulated, in the lacrimal glands of male NOD mice after onset of lacrimal hyposecretion and dacryoadenitis (lacrimal gland inflammation). Changes in the level of arginase 1 expression were confirmed by real‐time RT‐PCR and western blot analysis. Furthermore, non‐dacryoadenitis‐type NOD mice were used to investigate the relationships among arginase 1 expression, lacrimal hyposecretion and dacryoadenitis. Interestingly, these NOD mice retained the phenotype of dacryoadenitis with regard to tear secretion and arginase 1 expression level. An arginase 1 inhibitor reduced tear secretion and partially reduced saliva secretion in BALB/c mice. In conclusion, a non‐inflammatory factor, arginase 1, is involved in lacrimal hyposecretion in male NOD mice, regardless of dacryoadenitis status. These results shed light on the pathophysiological role of arginase 1 in SS (dry eye).
Did previous involvement in research affect recruitment of young people with cerebral palsy to a longitudinal study of transitional health care?
Authors: Garcia Jalón Elena Guiomar , Merrick Hanna , Colver Allan , Linden Mark 
Published: August 2020

ObjectiveTo assess whether being contacted about or participating in previous research and method of approaching potential participants affected recruitment to a transition study from child to adult healthcare services of young people with cerebral palsy (CP).Design and methodsYoung people with CP aged 14–18 years without severe intellectual impairment were identified from regional registers of CP in Northern Ireland and the North of England. χ2 and Mann-Whitney U tests were used to assess differences in CP and sociodemographic characteristics between those recruited and those who refused. Logistic regression was used to assess contact about and recruitment to previous research and method of approach as predictors of recruitment, controlling for demographic and CP characteristics.ResultsOf the 410 young people who were approached; 162 did not respond and of the 248 who responded, 96 (23%) were recruited. There were significant differences between those recruited and those who refused in age and number of previous studies they had participated in. Those who were older or who had previously been approached about research were more likely to be recruited to our study. However, those who had been recruited to previous studies were more likely to refuse to join our study.ConclusionsThe method of approach to potential participants did not affect recruitment. Older adolescents and those who had been approached about previous research were more likely to take part in our study, although there was evidence of research fatigue because if they had actually been recruited to the previous studies they were less likely to join our study. Recruitment of adolescents to studies remains challenging.
COVID-19 emergency response assessment study: a prospective longitudinal survey of frontline doctors in the UK and Ireland: study protocol
Authors: Roberts Tom , Daniels Jo , Hulme William , Horner Daniel , Lyttle Mark David , Samuel Katie , Graham Blair , Hirst Robert , Reynard Charles , Barrett Michael , Carlton Edward 
Published: August 2020

IntroductionThe COVID-19 pandemic is putting an unprecedented strain on healthcare systems globally. The psychological impact on frontline doctors of dealing with the COVID-19 pandemic is currently unknown. This longitudinal professional survey aims to understand the evolving and cumulative effects of working during the COVID-19 outbreak on the psychological well-being of doctors working in emergency departments (ED), intensive care units (ICU) and anaesthetics during the pandemic.Methods and analysisThis study is a longitudinal questionnaire-based study with three predefined time points spanning the acceleration, peak and deceleration phases of the COVID-19 pandemic.The primary outcomes are psychological distress and post-trauma stress as measured by the General Health Questionnaire-12 (GHQ-12) and Impact of Events Scale-Revised (IES-R). Data related to personal and professional characteristics will also be collected. Questionnaires will be administered prospectively to all doctors working in ED, ICU and anaesthetics in the UK and Ireland via existing research networks during the sampling period. Data from the questionnaires will be analysed to assess the prevalence and degree of psychological distress and trauma, and the nature of the relationship between personal and professional characteristics and the primary outcomes. Data will be described, analysed and disseminated at each time point; however, the primary endpoint will be psychological distress and trauma at the final time point.Ethics and disseminationEthical approval was obtained from the University of Bath, UK (ref: 4421), and Children’s Health Ireland at Crumlin, Ethics Committee. Regulatory approval from the Health Regulation Authority (UK), Health and Care Research Wales (IRAS: 281944).This study is limited by the fact that it focuses on doctors only and is survey based without further qualitative interviews of participants. It is expected this study will provide clear evidence of the psychological impact of COVID-19 on doctors and will allow present and future planning to mitigate against any psychological impact.Trial registration numberISRCTN10666798.
Variation in timely surgery for hip fracture by day and time of presentation: a nationwide prospective cohort study from the National Hip Fracture Database for England, Wales and Northern Ireland
Authors: Shah Anjali , Matharu Gulraj S , Inman Dominic , Fagan Elizabeth , Johansen Antony , Judge Andrew 
Published: August 2020

Background and ObjectiveSeveral studies report poorer quality healthcare for patients presenting at weekends. Our objective was to examine how timely surgery for patients with hip fracture varies with day and time of their presentation.MethodsThis population-based cohort study used 2017 data from the National Hip Fracture Database, which recorded all patients aged 60 years and over who presented with a hip fracture at a hospital in England, Wales and Northern Ireland. Provision of prompt surgery (surgery within 36 hours of presentation) was examined, using multivariable logistic regression with generalised estimating equations to derive adjusted risk ratios (RRs). Time was categorised into three 8-hour intervals (day: 08:00–15:59, evening: 16:00–23:59 and night: 00:00–07:59) for each day of the week. The model accounted for clustering by hospital and was adjusted by sex, age, fracture type, operation type, American Society of Anesthesiologists grade, preinjury mobility and location.ResultsWe studied 68 977 patients from 177 hospitals. The average patient presenting during the day on Friday or Saturday was significantly less likely to undergo prompt surgery (Friday during 08:00–15:59, RR=0.93, 95% CI 0.91 to 0.96; Saturday during 08:00–15:59, RR=0.91, 95% CI 0.88 to 0.94) than patients in the comparative category (Thursday, during the day). Patients presenting during the evening (16:00–23:59) were consistently significantly less likely to undergo prompt surgery, and the effect was more marked on Fridays and Saturdays (Friday during 16:00-23:59, RR=0.83, 95% CI 0.80 to 0.85; Saturday during 16:00–23:59, RR=0.81, 95% CI 0.78 to 0.85). Patients presenting overnight (00:00–07:59), except on Saturdays, were significantly more likely to undergo surgery within 36 hours (RR>1.07).ConclusionThe provision of prompt hip fracture surgery was complex, with evidence of both an ‘evening’ and a ‘night’ effect. Investigation of weekly variation in hip fracture care is required to help implement strategies to reduce the variation in timely surgery throughout the entire week.
D-dimer and the incidence of heart failure and mortality after acute myocardial infarction
Authors: Zhang Xiaoyuan , Wang Shanjie , Liu Jinxin , Wang Yini , Cai Hengxuan , Wang Duolao , Fang Shaohong , Yu Bo 
Published: August 2020

ObjectiveD-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. Few studies explore the association between baseline D-dimer levels and the incidence of heart failure (HF), all-cause mortality in an acute myocardial infarction (AMI) population. We aimed to explore this association.MethodsWe enrolled 4504 consecutive patients with AMI with complete data in a prospective cohort study and explored the association of plasma D-dimer levels on admission and the incidence of HF, all-cause mortality.ResultsOver a median follow-up of 1 year, 1112 (24.7%) patients developed in-hospital HF, 542 (16.7%) patients developed HF after hospitalisation and 233 (7.1%) patients died. After full adjustments for other relevant clinical covariates, patients with D-dimer values in quartile 3 (Q3) had 1.51 times (95% CI 1.12 to 2.04) and in Q4 had 1.49 times (95% CI 1.09 to 2.04) as high as the risk of HF after hospitalisation compared with patients in Q1. Patients with D-dimer values in Q4 had more than a twofold (HR 2.34; 95% CI 1.33 to 4.13) increased risk of death compared with patients in Q1 (p<0.001). But there was no association between D-dimer levels and in-hospital HF in the adjusted models.ConclusionsD-dimer was found to be associated with the incidence of HF after hospitalisation and all-cause mortality in patients with AMI.
Copper and zinc generated by the Aquascape IonGen pond clarifier system can be detrimental to koi (Cyprinus carpio) health
Authors: Tucker Emily , Gerlach Jamie , Curtean Azais , Passingham Kent , Murphy Lisa , Lewbart Gregory 
Published: August 2020

BackgroundCopper is frequently used as an algicide, and copper ion generators such as the Aquascape IonGen claim to be safe for use in systems containing fish. In 2012, a die‐off of koi (Cyprinus carpio) in a pond in Raleigh, North Carolina, occurred after the IonGen was added to the system.MethodsPhysical and postmortem examinations suggested that heavy metal toxicity was the likely cause of morbidity and mortality. This was supported by a heavy metal screening of the owners’ pond. Additional experiments were performed to determine if the IonGen produced toxic levels of copper and zinc.ResultsThe tank containing the IonGen had higher concentrations of copper and zinc, and copper levels exceeded those associated with toxicity in both hard and soft water.ConclusionThe results of this study indicate that ion generators might not be safe for fish, and copper should only be used as an algicide if concentrations are closely monitored.
GBT Analysis of Steel-Concrete Composite Beams: Recent Developments
Authors: Gonçalves Rodrigo , Camotim Dinar , Henriques David 
Published: August 2020

This paper reports the most recent developments concerning Generalized Beam Theory (GBT) formulations, and corresponding finite element implementations, for steel-concrete composite beams. These formulations are able to perform the following types of analysis: (i) materially nonlinear analysis, to calculate the beam load-displacement response, up to collapse, including steel plasticity, concrete cracking/crushing and shear lag effects, (ii) bifurcation (linear stability) analysis, to obtain local/distortional bifurcation loads and buckling mode shapes of beams subjected to negative (hogging) bending, accounting for shear lag and concrete cracking effects and (iii) long-term service analysis including creep, cracking and arbitrary cross-section deformation (which includes shear lag) effects. The potential (computational efficiency and accuracy) of the proposed GBT-based finite elements is illustrated through several numerical examples. For comparison purposes, results obtained with standard finite strip and shell/brick finite element models are provided.
Radiative backpropagation
Authors: Nimier-David Merlin , Speierer Sébastien , Ruiz Benoît , Jakob Wenzel 
Published: August 2020

Physically based differentiable rendering has recently evolved into a powerful tool for solving inverse problems involving light. Methods in this area perform a differentiable simulation of the physical process of light transport and scattering to estimate partial derivatives relating scene parameters to pixels in the rendered image. Together with gradient-based optimization, such algorithms have interesting applications in diverse disciplines, e.g., to improve the reconstruction of 3D scenes, while accounting for interreflection and transparency, or to design meta-materials with specified optical properties.
The most versatile differentiable rendering algorithms rely on reverse-mode differentiation to compute all requested derivatives at once, enabling optimization of scene descriptions with millions of free parameters. However, a severe limitation of the reverse-mode approach is that it requires a detailed transcript of the computation that is subsequently replayed to back-propagate derivatives to the scene parameters. The transcript of typical renderings is extremely large, exceeding the available system memory by many orders of magnitude, hence current methods are limited to simple scenes rendered at low resolutions and sample counts.

We introduce
radiative backpropagation
, a fundamentally different approach to differentiable rendering that does not require a transcript, greatly improving its scalability and efficiency. Our main insight is that reverse-mode propagation through a rendering algorithm can be interpreted as the solution of a continuous transport problem involving the partial derivative of radiance with respect to the optimization objective. This quantity is "emitted" by sensors, "scattered" by the scene, and eventually "received" by objects with differentiable parameters. Differentiable rendering then decomposes into two separate primal and adjoint simulation steps that scale to complex scenes rendered at high resolutions. We also investigated biased variants of this algorithm and find that they considerably improve both runtime and convergence speed. We showcase an efficient GPU implementation of radiative backpropagation and compare its performance and the quality of its gradients to prior work.
Unpaired motion style transfer from video to animation
Authors: Aberman Kfir , Weng Yijia , Lischinski Dani , Cohen-Or Daniel , Chen Baoquan 
Published: August 2020

Transferring the motion style from one animation clip to another, while preserving the motion content of the latter, has been a long-standing problem in character animation. Most existing data-driven approaches are supervised and rely on paired data, where motions with the same content are performed in different styles. In addition, these approaches are limited to transfer of styles that were seen during training.
In this paper, we present a novel data-driven framework for motion style transfer, which learns from an unpaired collection of motions with style labels, and enables transferring motion styles not observed during training. Furthermore, our framework is able to extract motion styles directly from videos, bypassing 3D reconstruction, and apply them to the 3D input motion.
Our style transfer network encodes motions into two latent codes, for content and for style, each of which plays a different role in the decoding (synthesis) process. While the content code is decoded into the output motion by several temporal convolutional layers, the style code modifies deep features via temporally invariant adaptive instance normalization (AdaIN).
Moreover, while the content code is encoded from 3D joint rotations, we learn a common embedding for style from either 3D or 2D joint positions, enabling style extraction from videos.
Our results are comparable to the state-of-the-art, despite not requiring paired training data, and outperform other methods when transferring previously unseen styles. To our knowledge, we are the first to demonstrate style transfer directly from videos to 3D animations - an ability which enables one to extend the set of style examples far beyond motions captured by MoCap systems.
Abstract PR17: Immunogenomic landscape of pediatric solid malignancies
Authors: Wei Jun S. , Brohl Andrew S. , Sindiri Sivasish , Song Young K. , Najaraj Sushma , Gangalapudi Vineela , Wen Xinyu , Ladanyi Marc , Khan Javed 
Published: August 2020

Abstract
Malignancy remains the leading cause of disease-related death in children. To identify potential tumor-driving molecular targets and immunogenomic profiles in pediatric cancers, we performed RNA-seq analysis on a cohort of 788 pediatric solid malignant tumors across 14 different diagnoses in conjunction with additional 147 normal tissues for comparison. Sequencing data were analyzed for expressed mutations, fusion events, and expressional patterns, providing therapeutic targets and rich cancer biology for these childhood cancers. Furthermore, we describe immunogenomic features of these solid tumors including immune cell infiltrate, neoantigen expression, expression of immunomodulatory molecules, and T-cell receptor repertoire. Across the cohort, we observed a striking correlation between the expressed neoantigen burden in tumors and enrichment of the effector immune signatures. Histology-specific immunogenomic patterns were also apparent. Several of the pediatric cancers such as alveolar soft part sarcoma and osteosarcoma exhibit rich immune cell infiltration and evidence for activated T-cell activities, whereas others such as Wilms’ tumors and synovial sarcoma generally have a very low T-cell infiltration. We demonstrate that RNA-seq is a powerful tool to identify clinically relevant and histology-specific recurrent mutations, novel oncogenic fusions, and translationally relevant immunogenomic patterns for pediatric cancers. This study also represents one of the largest of its type to date and provides a framework for future translational efforts in pediatric cancer.
This abstract is also being presented as Poster A69.
Citation Format: Jun S. Wei, Andrew S. Brohl, Sivasish Sindiri, Young K. Song, Sushma Najaraj, Vineela Gangalapudi, Xinyu Wen, Marc Ladanyi, Javed Khan. Immunogenomic landscape of pediatric solid malignancies [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr PR17.