bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil Extracellular Traps Induce Intestinal Damage and Thrombotic Tendency in Inflammatory Bowel Disease
Authors: Li Tao , Wang Chunxu , Liu Yingmiao , Li Baorong , Zhang Wujian , Wang Lixiu , Yu Muxin , Zhao Xinyi , Du Jingwen , Zhang Jinming , Dong Zengxiang , Jiang Tao , Xie Rui , Ma Ruishuang , Fang Shaohong , Zhou Jin , Shi Jialan 
Published: July 2019

Abstract

Background and Aims
Despite the presence of neutrophil extracellular traps [NETs] in inflamed colon having been confirmed, the role of NETs, especially the circulating NETs, in the progression and thrombotic tendency of inflammatory bowel disease [IBD] remains elusive. We extended our previous study to prove that NETs constitute a central component in the progression and prothrombotic state of IBD.

Methods
In all 48 consecutive patients with IBD were studied. Acute colitis was induced by the treatment of C57BL/6 mice with 3.5% dextran sulphate sodium [DSS] in drinking water for 6 days. Peripheral blood neutrophils and sera were collected from IBD patients and murine colitis models. Exposed phosphatidylserine [PS] was analysed with flow cytometry and confocal microscopy. Procoagulant activity was evaluated using clotting time, purified coagulation complex, and fibrin formation assays.

Results
We observed higher plasma NET levels and presence of NETs in colon tissue in patients with active IBD. More importantly, NETs were induced in mice with DSS colitis, and inhibition of NET release attenuated colitis as well as colitis-associated tumorigenesis. NET degradation through DNase administration decreased cytokine levels during DSS-induced colitis. In addition, DNase treatment also significantly attenuated the accelerated thrombus formation and platelet activation observed in DSS-induced colitis. NETs triggered PS-positive microparticle release and PS exposure on platelets and endothelial cells partially through TLR2 and TLR4, converting them to a procoagulant phenotype.

Conclusions
NETs exacerbate colon tissue damage and drive thrombotic tendency during active IBD. Strategies directed against NET formation may offer a potential therapeutic approach for the treatment of IBD.
A history of spine surgery predicts a poor outcome after hip arthroscopy
Authors: Feingold Jacob D , Heaps Braiden , Turcan Sava , Swartwout Erica , Ranawat Anil 
Published: July 2019

Abstract
This study compared patient reported outcomes scores (PROMs) between patients undergoing hip arthroscopy who have and have not had previous lumbar spine surgery. We aimed to determine if prior spine surgery impacts the outcome of hip arthroscopy. Data were prospectively collected and retrospectively reviewed in patients who underwent hip arthroscopy between 2010 and 2017. Twenty cases were identified for analysis and matched to a control group. Four PROMs were collected pre-operatively and between 6 months and 2 years post-operatively (mean 16.2 months): Modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), Hip Outcome Score-Sports (HOS-Sports) and the 33-item International Hip Outcome Tool (iHOT-33). Patients with previous spine surgery reported significantly worse (P-value &lt;0.001) post-operative scores on all PROMs and smaller net changes on all PROMs with the difference on the mHHS (P-value 0.007), HOS-Sport (P-value 0.009) and iHOT-33 (P-value 0.007) being significant. Subsequent analyses revealed that the type of spine surgery matters. Patients with a spine fusion reported worse post-operative scores on all PROMs compared with patients with a spine decompression surgery with the difference on the mHHS (P-value 0.001), HOS-ADL (P-value 0.011) and HOS-Sport (P-value 0.035) being significant. Overall, patients with prior decompression surgery experienced considerable improvements from hip arthroscopy whereas patients with a prior spine fusion reported poor post-operative outcomes. Given these results, it is vital that hip preservation surgeons understand the impact of the lumbar spine on the outcome of hip arthroscopy.
ZC4H2 stabilizes RNF220 to pattern ventral spinal cord through modulating Shh/Gli signaling
Authors: Ma Pengcheng , Song Ning-Ning , Cheng Xiaoning , Zhu Liang , Zhang Qiong , Zhang Long long , Yang Xiangcai , Wang Huishan , Kong Qinghua , Shi Deli , Ding Yu-Qiang , Mao Bingyu 
Published: July 2019

Abstract
ZC4H2 encodes a C4H2 type zinc-finger nuclear factor, the mutation of which has been associated with disorders with various clinical phenotypes in human, including developmental delay, intellectual disability and dystonia. ZC4H2 has been suggested to regulate spinal cord patterning in zebrafish as a co-factor for RNF220, an ubiquitin E3 ligase involved in Gli signaling. Here we showed that ZC4H2 and RNF220 knockout animals phenocopy each other in spinal patterning in both mouse and zebrafish, with mispatterned progenitor and neuronal domains in the ventral spinal cord. We showed evidence that ZC4H2 is required for the stability of RNF220 and also proper Gli ubiquitination and signaling in vivo. Our data provides new insights into the possible etiology of the neurodevelopmental impairments observed in ZC4H2-associated syndromes.
Automated Localization and Segmentation of Mononuclear Cell Aggregates in Kidney Histological Images Using Deep Learning
Authors: Lituiev Dmytro S. , Cha Sung Jik , Chin Aaron , Glicksberg Benjamin S. , Bishara Andrew , Dobi Dejan , Cheng Ruizhe (Ryan) , Sohn Jae Ho , Laszik Zoltan , Hadley Dexter 
Published: July 2019

AbstractAllograft rejection is a major concern in kidney transplantation. Inflammatory processes in patients with kidney allografts involve various patterns of immune cell recruitment and distributions. Lymphoid aggregates (LAs) are commonly observed in patients with kidney allografts and their presence and localization may correlate with severity of acute rejection. Alongside with other markers of inflammation, LAs assessment is currently performed by pathologists manually in a qualitative way, which is both time consuming and far from precise. Here we present the first automated method of identifying LAs and measuring their densities in whole slide images of transplant kidney biopsies. We trained a deep convolutional neural network based on U-Net on 44 core needle kidney biopsy slides, monitoring loss on a validation set (n=7 slides). The model was subsequently tested on a hold-out set (n=10 slides). We found that the coarse pattern of LAs localization agrees between the annotations and predictions, which is reflected by high correlation between the annotated and predicted fraction of LAs area per slide (Pearson R of 0.9756). Furthermore, the network achieves an auROC of 97.78 ± 0.93% and an IoU score of 69.72 ± 6.24 % per LA-containing slide in the test set. Our study demonstrates that a deep convolutional neural network can accurately identify lymphoid aggregates in digitized histological slides of kidney. This study presents a first automatic DL-based approach for quantifying inflammation marks in allograft kidney, which can greatly improve precision and speed of assessment of allograft kidney biopsies when implemented as a part of computer-aided diagnosis system.
Mechanisms of Arrhythmogenicity in Hypertrophic Cardiomyopathy: Insight from Noninvasive Electrocardiographic Imaging
Authors: Perez-Alday Erick A. , Haq Kazi T. , German David M. , Hamilton Christopher , Johnson Kyle , Phan Francis , Rogovoy Nichole M. , Yang Katherine , Wirth Ashley , A.Thomas Jason , Dalouk Khidir , Fuss Cristina , Ferencik Maros , Heitner Stephen , Tereshchenko Larisa G. 
Published: July 2019

AbstractBackgroundMechanisms of arrhythmogenicity in hypertrophic cardiomyopathy (HCM) are not well understood.ObjectiveTo characterize an electrophysiological substrate of HCM in comparison to ischemic cardiomyopathy (ICM), or healthy individuals.MethodsWe conducted a prospective case-control study. The study enrolled HCM patients at high risk for ventricular tachyarrhythmia (VT) (n=10; age 61±9 y; left ventricular ejection fraction (LVEF) 60±9%), and three comparison groups: healthy individuals (n=10; age 28±6 y; LVEF>70%), ICM patients with LV hypertrophy (LVH) and known VT (n=10; age 64±9 y; LVEF 31±15%), and ICM patients with LVH and no known VT (n=10; age 70±7y; LVEF 46±16%). All participants underwent 12-lead ECG, cardiac CT or MRI, and 128-electrode body surface mapping (BioSemi ActiveTwo, Netherlands). Non-invasive voltage and activation maps were reconstructed using the open-source SCIRun (University of Utah) inverse problem-solving environment.ResultsIn the epicardial basal anterior segment, HCM patients had the greatest ventricular activation dispersion [16.4±5.5 vs. 13.1±2.7 (ICM with VT) vs. 13.8±4.3 (ICM no VT) vs. 8.1±2.4 ms (Healthy); P=0.0007], the largest unipolar voltage [1094±211 vs. 934±189 (ICM with VT) vs. 898±358 (ICM no VT) vs. 842±90 µV (Healthy); P=0.023], and the greatest voltage dispersion [median(interquartile range) 215(161-281) vs. 189(143-208) (ICM with VT) vs. 158(109-236) (ICM no VT) vs. 110(106-168)µV (Healthy); P=0.041]. Differences were also observed in other endo-and epicardial basal and apical segments.ConclusionHCM is characterized by a greater activation dispersion in basal segments, a larger voltage, and a larger voltage dispersion through LV.
Robustifying genomic classifiers to batch effects via ensemble learning
Authors: Zhang Yuqing , Johnson W. Evan , Parmigiani Giovanni 
Published: July 2019

AbstractGenomic data are often produced in batches due to practical restrictions, which may lead to unwanted variation in data caused by discrepancies across processing batches. Such “batch effects” often have negative impact on downstream biological analysis and need careful consideration. In practice, batch effects are usually addressed by specifically designed software, which merge the data from different batches, then estimate batch effects and remove them from the data. Here we focus on classification and prediction problems, and propose a different strategy based on ensemble learning. We first develop prediction models within each batch, then integrate them through ensemble weighting methods. In contrast to the typical approach of removing batch effects from the merged data, our method integrates predictions rather than data. We provide a systematic comparison between these two strategies, using studies targeting diverse populations infected with tuberculosis. In one study, we simulated increasing levels of heterogeneity across random subsets of the study, which we treat as simulated batches. We then use the two methods to develop a genomic classifier for the binary indicator of disease status. We evaluate the accuracy of prediction in another independent study targeting a different population cohort. We observed a turning point in the level of heterogeneity, after which our strategy of integrating predictions yields better discrimination in independent validation than the traditional method of integrating the data. These observations provide practical guidelines for handling batch effects in the development and evaluation of genomic classifiers.
Volumetric Segmentation of Cell Cycle Markers in Confocal Images
Authors: Khan Faraz Ahmad , Voß Ute , Pound Michael P , French Andrew P 
Published: July 2019

I.ABSTRACTUnderstanding plant growth processes is important for many aspects of biology and food security. Automating the observations of plant development – a process referred to as plant phenotyping – is increasingly important in the plant sciences, and is often a bottleneck. Automated tools are required to analyse the data in images depicting plant growth. In this paper, a deep learning approach is developed to locate fluorescent markers in 3D timeseries microscopy images. The approach is not dependant on marker morphology; only simple 3D point location annotations are required for training. The approach is evaluated on an unseen timeseries comprising several volumes, capturing growth of plants. Results are encouraging, with an average recall of 0.97 and average F-score of 0.78, despite only a very limited number of simple training annotations. In addition, an in-depth analysis of appropriate loss functions is conducted. To accompany [the finally-published] paper we are releasing the 4D point annotation tool used to generate the annotations, in the form of a plugin for the popular ImageJ (Fiji) software. Network models will be released online.
Functional cortico-subcortical reorganization after complete hemispheric disconnection for intractable epilepsy
Authors: Blauwblomme Thomas , Demertzi Athena , Tacchela Jean-Marc , Fillon Ludovic , Bourgeois Marie , Lositto Emma , Eisermann Monika , Marinazzo Daniele , Raimondo Federico , Alcauter Sarael , Van De Steen Frederik , Colenbier Nigel , Laureys Steven , Dangouloff-Ros Volodia , Naccache Lionel , Boddaert Nathalie , Nabbout Rima 
Published: July 2019

AbstractHemispherotomy is a treatment for drug-resistant epilepsy with the whole hemisphere involved in seizure onset. As recovery mechanisms are still debated, we characterize functional reorganization with multimodal MRI in two children operated on the right hemisphere (RH). We found that interhemispheric functional connectivity was abolished in both patients. The healthy left hemispheres (LH) displayed focal hyperperfusion in motor and limbic areas, and preserved network-level organization. The disconnected RHs were hypoperfused despite sustained network-level organization. Functional connectivity was increased in the left thalamo-cortical loop and between the cerebelli. The classification probability of the RH corresponding to a minimally conscious state was smaller than for the LH. We conclude that after hemispherotomy, neurological rehabilitation is sustained by cortical disinhibition and reinforcement of connectivity driven by subcortical structures in the remaining hemisphere. Our results highlight the effect of vascularization on functional connectivity and raise inquiries about the conscious state of the isolated hemisphere.
Network analysis of the papaya orchard virome from two agroecological regions of Chiapas, Mexico
Authors: Alcalá-Briseño Ricardo I. , Casarrubias-Castillo Kena , López-Ley Diana , Garrett Karen A. , Silva-Rosales Laura 
Published: July 2019

AbstractThe study of complex ecological interactions - such as those among host, pathogen, and vector communities - can help to explain host ranges and the emergence of novel pathogens. The analysis of community structures using bipartite networks describe the associations between two trophic levels, for example plants and pollinators, or hosts and parasitoids. Bipartite networks represent interactions (links) occurring only between nodes in different levels - in our case, between viruses and hosts. We evaluated the viromes of papaya orchards (papaya, weeds, and insects) from intensive production of papaya in the Pacific Coastal Plain and the Central Depression of Chiapas, Mexico. Samples of papaya cultivar Maradol, which, like most cultivars, is susceptible to papaya ringspot virus (PRSV), were categorized by symptoms by local farmers (papaya ringspot symptoms, non-PRSV symptoms, or no symptoms). These analyses revealed the presence of 61 viruses, where only four species were shared among both physiographic regions. Nearly 52 complete viral genome sequences were recovered, of which 16 showed homology to known viruses, and 36 shared similarities with different genera includingPotyvirus,Comovirus, andTombusvirus(RNA viruses), andBegomovirusandMastrevirus(DNA viruses). We analyzed the network of associations between viruses and host-location combinations, and described ecological properties of the network, such as asymmetry in interactions and nestedness compared to null models. Understanding the network structure informs management strategies, and advances understanding of interactions of hosts and viruses in the agroecological landscape.ImportanceVirus-virus interactions in plants can modify host symptoms. As a result, disease management strategies may be unsuccessful if they are based solely on visual assessment and diagnostic assays for known individual viruses. Papaya ringspot virus is an important limiting factor for papaya production, and likely has interactions with other viruses that are not yet known. Using high-throughput sequencing, we recovered known and novel RNA and DNA viruses from papaya orchards in Chiapas, Mexico, categorized by host and, in the case of papaya, symptom type: asymptomatic papaya, papaya with ringspot virus symptoms, papaya with non-ringspot symptoms, weeds, and insects. Using network analysis, we demonstrated virus associations within and among host types, and described the ecological community patterns. Recovery of viruses from weeds and asymptomatic papaya suggests the need for additional management attention. These analyses contribute to the understanding of the community structure of viruses in the agroecological landscape.
Caspase-8 Modulates Angiogenesis By Regulating A Cell Death Independent Pathway In Endothelial Cells
Authors: Tisch Nathalie , Freire-Valls Aida , Yerbes Rosario , Paredes Isidora , La Porta Silvia , Wang Xiaohong , Martín-Pérez Rosa , Castro Laura , Wong Wendy Wei-Lynn , Coultas Leigh , Strilic Boris , Gröne Hermann-Josef , Hielscher Thomas , Mogler Carolin , Adams Ralf , Heiduschka Peter , Claesson-Welsh Lena , Mazzone Massimiliano , López-Rivas Abelardo , Schmidt Thomas , Augustin Hellmut G. , de Almodovar Carmen Ruiz 
Published: July 2019

ABSTRACTDuring developmental angiogenesis blood vessels grow and remodel to ultimately build a hierarchical vascular network. Whether and how cell death signaling molecules contribute to blood vessel formation is still not well understood. Caspase-8 (Casp-8), a key protease in the extrinsic cell death-signaling pathway, regulates both cell death via apoptosis and necroptosis. Here we show that expression of Casp-8 in endothelial cells (ECs) is required for proper postnatal angiogenesis. EC specific Casp-8 knockout pups (Casp-8ECko) have reduced retinal angiogenesis, as the loss of Casp-8 reduced EC proliferation, sprouting and migration independent of its cell death function. Instead, the loss of Casp-8 caused hyperactivation of p38 mitogen-activated protein kinase (MAPK) downstream of receptorinteracting serine/threonine-protein kinase 3 (RIPK3) and destabilization of VE-cadherin at EC junctions. In a mouse model of oxygen-induced retinopathy (OIR), resembling retinopathy of prematurity (ROP), loss of Casp-8 in ECs is beneficial, as pathological neovascularization was reduced in Casp-8ECkopups. Taken together, we identify that Casp-8 signals in a cell-death independent manner in ECs during postnatal and pathological blood vessel formation.
Plasma-derived HIV Nef+ exosomes persist in ACTG384 study participants despite successful virological suppression
Authors: Raymond Andrea D. , Lang Michelle J. , Chu Jane , Campbell-Sims Tamika , Khan Mahfuz , Bond Vincent C. , Pollard Richard B. , Asmuth David M. , Powell Michael D. 
Published: July 2019

AbstractHuman Immunodeficiency Virus (HIV) accessory protein Negative factor (Nef) is detected in the plasma of HIV+ individuals associated with exosomes. The role of Nef+ exosomes (exNef) in HIV pathogenesis is unknown. We perform a retrospective longitudinal analysis to determine correlative clinical associations of exNef plasma levels in ARV-treated HIV+ patients with or without immune recovery. exNef concentration in a subset of AIDS Clinical Trial Group (ACTG) 384 participants with successful virological suppression and with either high (Δ >100 CD4 cell recovery/High Immunological Responders (High-IR) or low (Δ ≤100 CD4 cell recovery/ Low Immunologic Responders (Low-IR) immunologic recovery was measured and compared for study weeks 48, 96, and 144. CD4 recovery showed a negative correlation with exNef at study week 144 (r= −0.3573, *p=.0366). Plasma exNef concentration in high IRs negatively correlated with naïve CD4 count and recovery (r= −0.3249, *p= 0. 0348 (High-IR); r =0.2981, *p= #0.0513 (Low-IR)). However, recovery of CD4 memory cells positively correlated with exNef (r =.4534, *p=.0358) inLow-IRs but not inHigh-IRs. Regimen A (Didanosine, Stavudine, Efavirenz) lowered exNef levels in IRs by 2-fold compared to other regimens. Nef+ exosomes persist in ART-treated HIV+ individuals despite undetectable viral loads, negatively correlates with naive and memory CD4 T cell restoration and may be associated with reduced immunological recovery. Taken together, these data suggest that exNef may represent a novel mechanism utilized by HIV to promote immune dysregulation.
RootNav 2.0: Deep Learning for Automatic Navigation of Complex Plant Root Architectures
Authors: Yasrab Robail , Atkinson Jonathan A , Wells Darren M , French Andrew P , Pridmore Tony P , Pound Michael P 
Published: July 2019

AbstractWe present a new image analysis approach that provides fully-automatic extraction of complex root system architectures from a range of plant species in varied imaging setups. Driven by modern deep-learning approaches,RootNav 2.0replaces previously manual and semi-automatic feature extraction with an extremely deep multi-task Convolutional Neural Network architecture. The network has been designed to explicitly combine local pixel information with global scene information in order to accurately segment small root features across high-resolution images. In addition, the network simultaneously locates seeds, and first and second order root tips to drive a search algorithm seeking optimal paths throughout the image, extracting accurate architectures without user interaction. The proposed method is evaluated on images of wheat (Triticum aestivumL.) from a seedling assay. The results are compared with semi-automatic analysis via the originalRootNavtool, demonstrating comparable accuracy, with a 10-fold increase in speed. We then demonstrate the ability of the network to adapt to different plant species via transfer learning, offering similar accuracy when transferred to anArabidopsis thalianaplate assay. We transfer for a final time to images ofBrassica napusfrom a hydroponic assay, and still demonstrate good accuracy despite many fewer training images. The tool outputs root architectures in the widely accepted RSML standard, for which numerous analysis packages exist (http://rootsystemml.github.io/), as well as segmentation masks compatible with other automated measurement tools.
A cortico-collicular pathway for motor planning in a memory-dependent perceptual decision task
Authors: Duan Chunyu A. , Pan Yuxin , Ma Guofen , Zhou Taotao , Zhang Siyu , Xu Ning-long 
Published: July 2019

ABSTRACTSurvival in a dynamic environment requires animals to plan future actions based on past sensory evidence. However, the neural circuit mechanism underlying this crucial brain function, referred to as motor planning, remains unclear. Here, we employ projection-specific imaging and perturbation methods to investigate the direct pathway linking two key nodes in the motor planning network, the secondary motor cortex (M2) and the midbrain superior colliculus (SC), in mice performing a memory-dependent perceptual decision task. We find dynamic coding of choice information in SC-projecting M2 neurons during motor planning and execution, and disruption of this information by inhibiting M2 terminals in SC selectively impaired decision maintenance. Furthermore, cell-type-specific optogenetic circuit mapping shows that M2 terminals modulate both excitatory and inhibitory SC neurons with balanced synaptic strength. Together, our results reveal the dynamic recruitment of the premotor-collicular pathway as a circuit mechanism for motor planning.