bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversal of Surfactant Protein B Deficiency in Patient Specific Human Induced Pluripotent Stem Cell Derived Lung Organoids by Gene Therapy
Authors: Leibel Sandra Lawrynowicz , Winquist Alicia , Tseu Irene , Wang Jinxia , Luo Daochun , Shojaie Sharareh , Nathan Neal , Snyder Evan , Post Martin 
Published: September 2019

AbstractSurfactant protein B (SFTPB) deficiency is a fatal disease affecting newborn infants. Surfactant is produced by alveolar type II cells which can be differentiated in vitro from patient specific induced pluripotent stem cell (iPSC)-derived lung organoids. Here we show the differentiation of patient specific iPSCs derived from a patient with SFTPB deficiency into lung organoids with mesenchymal and epithelial cell populations from both the proximal and distal portions of the human lung. We alter the deficiency by infecting the SFTPB deficient iPSCs with a lentivirus carrying the wild type SFTPB gene. After differentiating the mutant and corrected cells into lung organoids, we show expression of SFTPB mRNA during endodermal and organoid differentiation but the protein product only after organoid differentiation. We also show the presence of normal lamellar bodies and the secretion of surfactant into the cell culture medium in the organoids of lentiviral infected cells. These findings suggest that a lethal lung disease can be targeted and corrected in a human lung organoid model in vitro.
Renoprotective effects of a novel cMet agonistic antibody on kidney fibrosis
Authors: Kim Yong Chul , Lee Junghun , An Jung Nam , Kim Jin Hyuk , Choi Young-Wook , Li Lilin , Kwon Sang Ho , Lee Mi-Young , Lee Boeun , Jeong Jae-Gyun , Yu Seung-Shin , Lim Chun Soo , Kim Yon Su , Kim Sunyoung , Yang Seung Hee , Lee Jung Pyo 
Published: September 2019

AbstractHepatocyte growth factor (HGF) and its receptor, cMet, activate biological pathways necessary for repair and regeneration following kidney injury. Because HGF is a highly unstable molecule in its biologically active form, we asked whether a monoclonal antibody (Ab) that displays full agonist activity at the receptor could protect the kidney from fibrosis. We attempted to determine whether the cMet agonistic Ab might reduce fibrosis, the final common pathway for chronic kidney diseases (CKD). A mouse model of kidney fibrosis disease induced by unilateral ureteral obstruction was introduced and subsequently validated with primary cultured human proximal tubular epithelial cells (PTECs). In kidney biopsy specimens from patients with CKD, cMet immunohistochemistry staining showed a remarkable increase compared with patients with normal renal functions. cMet Ab treatment significantly increased the levels of phospho-cMet and abrogated the protein expression of fibrosis markers such as fibronectin, collagen 1, and αSMA as well as Bax2, which is a marker of apoptosis triggered by recombinant TGF-β1 in PTECs. Remarkably, injections of cMet Ab significantly prevented kidney fibrosis in obstructed kidneys as quantified by Masson trichrome staining. Consistent with these data, cMet Ab treatment decreased the expression of fibrosis markers, such as collagen1 and αSMA, whereas the expression of E-cadherin, which is a cell-cell adhesion molecule, was restored. In conclusion, cMet-mediated signaling may play a considerable role in kidney fibrosis. Additionally, the cMet agonistic Ab may be a valuable substitute for HGF because it is more easily available in a biologically active, stable, and purified form.
Risk factors and treatment outcomes of severe Clostridioides difficile infection in Singapore
Authors: Tay H. L. , Chow A. , Ng T. M. , Lye D. C. 
Published: September 2019

AbstractSevere Clostridioides difficile infection (CDI) is associated with poorer outcomes. We aimed to identify risk factors and treatment outcomes of severe CDI. This was a retrospective cohort study. Eligible patients from January to December 2012 were recruited. Severity definitions were in accordance with SHEA/IDSA 2010 guideline. Treatment outcomes were (1) diarrhoea persistence, (2) CDI recurrence, (3) major complications despite treatment and (4) 30-day mortality. Two hundred and seventy-two patients were included and 40% had severe CDI. High APACHE II score (aOR 1.112, 95% CI 1.014–1.219; p < 0.05), high C-reactive protein (aOR 1.011; 95% CI 1.004–1.019; p < 0.01) and carbapenem usage in past 90 days (aOR 3.259; 95% CI 1.105–9.609; p < 0.05) were independent risk factors of severe CDI. Majority received oral metronidazole as sole treatment (92.6% for mild-moderate, 83.9% for severe, 77% for severe-complicated). Diarrhoea persistence was 32% versus 50% (p < 0.01), CDI recurrence 16.6% versus 16.5% (p > 0.05), major complications 1.2% versus 11% (p < 0.001) and 30-day mortality 7.4% versus 20.2% (p < 0.01) in mild-moderate CDI and severe CDI groups respectively. Oral metronidazole for severe CDI was associated with persistent diarrhoea, major complications and mortality. Risk factors for severe CDI can guide doctors in diagnosing severe CDI earlier and instituting oral vancomycin treatment to improve outcomes from severe CDI.
Maize leaf-removal: A new agronomic approach to increase dry matter, flower number and seed-yield of soybean in maize soybean relay intercropping system
Authors: Raza Muhammad Ali , Feng Ling Yang , van der Werf Wopke , Iqbal Nasir , Khalid Muhammad Hayder Bin , Chen Yuan Kai , Wasaya Allah , Ahmed Shoaib , Ud Din Atta Mohi , Khan Ahsin , Ahmed Saeed , Yang Feng , Yang Wenyu 
Published: September 2019

AbstractShading conditions adversely affect flower-number and pod-number of soybeans under maize-soybean relay-intercropping (MSR). Here we reveal that leaf-removal from maize-canopy improves the photosynthetically active radiation (PAR) transmittance and dry-matter production (DMP) of soybean (especially during the co-growth phase), and compensates the maize seed-yield loss by considerably increasing soybean seed-yield. In a two-year experiment with MSR, maize-plants were subjected to different leaf-removal treatments to increase the PAR-transmittance of soybean; removal of the topmost two-leaves (R2), four-leaves (R4), six-leaves (R6), with no-removal of leaves (R0). Leaf-removal treatments improved the PAR-transmittance, photosynthetic-rate, and morphological-characteristics of soybean under MSR. At 90 days after sowing, the dry-matter of pods, and seeds was increased by 25%, and 32%, respectively under R6 than R0. Importantly, enhanced PAR-transmittance and DMP under R6 enabled soybean to initiate a greater number of flowers 182.2 plant−1 compared to 142.7 plant−1 under R0, and it also decreased the flower-abscission (by 13%, from 54.9% under R0 to 47.6% under R6). These positive responses increased the pod-number by 49% and seed-number by 28% under R6 than R0. Overall, under R6, relay-intercropped soybean produced 78% of sole-soybean seed-yield, and relay-intercropped maize produced 81% of sole-maize seed-yield and achieved the land equivalent ratio of 1.59.
Subsidies from anthropogenic resources alter diet, activity, and ranging behavior of an apex predator (Canis lupus)
Authors: Petroelje Tyler R. , Belant Jerrold L. , Beyer Dean E. , Svoboda Nathan J. 
Published: September 2019

AbstractAcquisition of resources can be costly and individuals are predicted to optimize foraging strategies to maximize net energy gain. Wolves (Canis lupus) would be expected to scavenge on subsidies from anthropogenic resources when these resources provide an energetic benefit over the capture of wild prey. We examined the effects of subsidies from anthropogenic resources in the form of livestock carcass dumps (LCDs) on wolf space use, activity, tortuosity, and diet in portions of North America’s northern hardwood/boreal ecosystem. We fitted 19 wolves with global positioning system collars during May–August of 2009–2011 and 2013–2015. Wolves with LCDs within their home ranges used areas adjacent to LCDs greater than non-LCD sites and had decreased home ranges and activity as compared to wolves without LCDs in their home ranges. Additionally, cattle comprised at least 22% of wolf diet from scavenging in areas with LCDs present as compared to no cattle in the diet of wolves without access to LCDs. Subsidies from anthropogenic resources in the form of LCDs can serve as attractants for wolves and alter wolf diet, activity, and ranging behavior. Apex predators may alter their behavior where subsidies from anthropogenic resources occur and management of these subsidies should be considered when attempting to reduce the impacts of humans on wolf behavior.
Increased Granulopoiesis in the Bone Marrow following Epstein-Barr Virus Infection
Authors: Katahira Yasuhiro , Higuchi Hiroshi , Matsushita Hiromichi , Yahata Takashi , Yamamoto Yuichiro , Koike Ryo , Ando Kiyoshi , Sato Katsuaki , Imadome Ken-Ichi , Kotani Ai 
Published: September 2019

AbstractEpstein-Barr virus (EBV) is associated with several disorders. EBV is known to modulate the proliferation and survival of hematopoietic cells such as B cells and T cells in human. However, the effects of EBV on hematopoiesis itself have not been investigated. To study EBV infection in murine models, their hematopoiesis must be humanized, since EBV infection is limited only in primates. To engraft the human hematopoiesis, NOD/Shi-scid-IL2rγnull (NOG) mice were used. Usually, the hematopoiesis humanized mice reconstitute only lymphoid cells, but myeloid cells are not. However, we revealed human macrophages (hMφ) and their precursor monocytes were increased in peripheral tissues of EBV-infected mice. Furthermore, our previous report indicated Mφ accumulation in spleen was essential for development of EBV-positive tumors, suggesting that EBV modulates human hematopoiesis in order to thrive. Interestingly, we revealed a dramatic increase of immature granulocytes only in bone marrow of EBV-infected mice. In addition, GM-CSF, a cytokine that is essential for differentiation of the myeloid lineage, was significantly increased in EBV-infected mice. These results were also reproduced in patients with EBV-related disorders. We suggest that the hematopoietic alterations during EBV-infection might contribute immune suppression to the development and exacerbation of EBV-related disorders.
Clinical outcomes of an intraoperative surgical margin assessment using the fresh frozen section method in patients with invasive breast cancer undergoing breast-conserving surgery – a single center analysis
Authors: Nowikiewicz Tomasz , Śrutek Ewa , Głowacka-Mrotek Iwona , Tarkowska Magdalena , Żyromska Agnieszka , Zegarski Wojciech 
Published: September 2019

AbstractBreast conserving treatment (BCT) is a safe standard therapeutic method in patients with early invasive breast cancer. However, it is associated with an increased risk of residual neoplastic tissues in surgical margins. The aim of this study was to assess the outcome of the use of the intraoperative pathologic analysis by the frozen section (FS) method for evaluation of the extent of the primary lumpectomy. The study concerns a retrospective analysis of a group of 1102 patients who underwent BCT between Jan 2015 and Dec 2016. The assessment focused on the frequency of the intraoperative pathologic analysis of the primary lumpectomy extent (fresh frozen section method). The influence of the BCT specimen analysis method on the free margins width, as well as the rate and the cause of reoperation were evaluated. The intraoperative lumpectomy evaluation was performed in 45.8% (505/1102) of patients (Group I), while in the remaining 54.2% of the cases it was decided to abandon this procedure (Group II). Although in 72 (14.3%) patients the intraoperative analysis gave negative results, the margins contained residual tumor tissue (vs. 16.9% in Group II). In Group I, conversion from the previously planned BCT to mastectomy was necessary in 5.9% (30/505) patients (vs. 9.7% in Group II). The duration of surgery was 48.9 ± 17.3 minutes (Group I) and 42.9 ± 13.6 minutes (Group II). In patients undergoing BCT, the use of the intraoperative pathologic analysis by the FS method resulted in a reduction of the total number of reoperations performed due to residual tumor found in the margins following the primary lumpectomy. However, it statistically significantly extended the duration of the surgery.
Within-host evolution of bovine Staphylococcus aureus selects for a SigB-deficient pathotype characterized by reduced virulence but enhanced proteolytic activity and biofilm formation
Authors: Marbach Helene , Mayer Katharina , Vogl Claus , Lee Jean Y. H. , Monk Ian R. , Sordelli Daniel O. , Buzzola Fernanda R. , Ehling-Schulz Monika , Grunert Tom 
Published: September 2019

AbstractStaphylococcus aureus is a major cause of bovine mastitis, commonly leading to long-lasting, persistent and recurrent infections. Thereby, S. aureus constantly refines and permanently adapts to the bovine udder environment. In this work, we followed S. aureus within-host adaptation over the course of three months in a naturally infected dairy cattle with chronic, subclinical mastitis. Whole genome sequence analysis revealed a complete replacement of the initial predominant variant by another isogenic variant. We report for the first time within-host evolution towards a sigma factor SigB-deficient pathotype in S. aureus bovine mastitis, associated with a single nucleotide polymorphism in rsbU (G368A → G122D), a contributor to SigB-functionality. The emerged SigB-deficient pathotype exhibits a substantial shift to new phenotypic traits comprising strong proteolytic activity and poly-N-acetylglucosamine (PNAG)-based biofilm production. This possibly unlocks new nutritional resources and promotes immune evasion, presumably facilitating extracellular persistence within the host. Moreover, we observed an adaptation towards attenuated virulence using a mouse infection model. This study extends the role of sigma factor SigB in S. aureus pathogenesis, so far described to be required for intracellular persistence during chronic infections. Our findings suggest that S. aureus SigB-deficiency is an alternative mechanism for persistence and underpin the clinical relevance of staphylococcal SigB-deficient variants which are consistently isolated during human chronic infections.
Cell Type Classification and Unsupervised Morphological Phenotyping From Low-Resolution Images Using Deep Learning
Authors: Yao Kai , Rochman Nash D. , Sun Sean X. 
Published: September 2019

AbstractConvolutional neural networks (ConvNets) have proven to be successful in both the classification and semantic segmentation of cell images. Here we establish a method for cell type classification utilizing images taken with a benchtop microscope directly from cell culture flasks, eliminating the need for a dedicated imaging platform. Significant flask-to-flask morphological heterogeneity was discovered and overcome to support network generalization to novel data. Cell density was found to be a prominent source of heterogeneity even when cells are not in contact. For the same cell types, expert classification was poor for single-cell images and better for multi-cell images, suggesting experts rely on the identification of characteristic phenotypes within subsets of each population. We also introduce Self-Label Clustering (SLC), an unsupervised clustering method relying on feature extraction from the hidden layers of a ConvNet, capable of cellular morphological phenotyping. This clustering approach is able to identify distinct morphological phenotypes within a cell type, some of which are observed to be cell density dependent. Finally, our cell classification algorithm was able to accurately identify cells in mixed populations, showing that ConvNet cell type classification can be a label-free alternative to traditional cell sorting and identification.
Alignment and Calibration of the Belle II Detector
Authors: Bilka Tadeáၡ , Chilikin Kirill , Dossett David , Guan Yinghui , Kandra Jakub , Kleinwort Claus , Sevior Martin 
Published: September 2019

In spring 2018 the SuperKEKB electron-positron collider at High Energy Accelerator Research Organization (KEK, Tsukuba, Japan) will deliver its first collisions to the Belle II experiment. The aim of Belle II is to collect a data sample 50 times larger than the previous generation of BFactories taking advantage of the unprecedented SuperKEKB design luminosity of 8×1035cm-2s-1. The Belle II detector will allow to conduct precise measurements in the harsh collider environment, probing for signs of physics beyond the standard model at the precision frontier.
In order to deliver data suitable for physics analysis, the detector has to be properly calibrated on a regular basis. Among other calibrations the detector alignment plays a key role. For example, precise measurements of time dependent CP-violation rely on the accurate alignment of the new vertex detector, as well as on the determination of the beamspot position and size. To automate the calibration procedures and manage the large amount of data and processing power needed for detector calibration, a software framework has been developed which allows to define the complete workflow and to execute it on a computing cluster. The framework integrates the Millepede II algorithm to solve the large minimization problem emerging in the track-based alignment and calibration of the pixel and strip detector, the central drift chamber, and the muon system.
The first collision data will allow to test and to further improve and tune the alignment and calibration procedures. Although the vertexing capabilities will be limited due to the installation of only a small slice of the full vertex detector, the commissioning phase will allow to test most of the alignment procedure features and to prepare for the full operation. We will present the results achieved during the first data taking, the experience gained and the plans for the first physics run with the full detector.
Research and Exploit of Resource Sharing Strategy at IHEP
Authors: JIANG Xiaowei , Shi Jingyan , Zou Jiaheng , Hu Qingbao , Du Ran , Sun Zhenyu 
Published: September 2019

At IHEP (Institute of High Energy Physics, Chinese Academy of Sciences), computing resources are contributed by different experiments including BES, JUNO, DYW, HXMT, etc. The resources were divided into different partitions to satisfy the dedicated experiment data processing requirements. IHEP had a local Torqu&Maui cluster with 50 queues serving for above 10 experiments. The separated resource partitions leaded to imbalance resource load. In a typical situation, BES resource partition was quite busy without free slot but still with lots of jobs in idle, while JUNO resources are free and wasted seriously.
After moving resources from Torque&Maui to HTCondor in 2016, job scheduling efficiency has been improved a lot. In order to balance the imbalance resource load, we designed an efficient sharing strategy to improve the overall resourceutilization. We created an unified pool shared by all experiments. For each experiment, resources are divided into two parts: dedicated resource and sharing resource. The slots in dedicated resource only run jobs from its own experiment, and the slots in sharing resource are shared by jobs from all experiments. Default ratio of dedicated resource to sharing resource is 1:4. To maximize the sharing effectiveness, the ratio is dynamically adjusted between 0:5 and 4:1 based on the number of jobs submitted by each experiment.
We have developed a central control system to decide how many resources can be allocated to each experiment group. This system is implemented at two sides: server side and client side. A management database is built at server side, which is storing resource, group and experiment information. Once the sharing ratio needs to be adjusted, resource group will be changed and updated into database. The resource group information is published to the server buffer in real-time. The client periodically pulls resource group information from server buffer via https protocol And resource scheduling configuration at client side is changed based on the resource group information. With this method, share ratio can be modified and deployed dynamically.
Sharing strategy is implemented with HTCondor. ClassAd mechanism and accounting-group in HTCondor facilitate to utilizethe sharing strategy at IHEP computing cluster. With the sharing strategy, resource usage has been improved dramatically.
Modeling and Simulation of Load Balancing Strategies for Computing in High Energy Physics
Authors: Caspart René , Firnkes Patrick , Giffels Manuel , Koziolek Anne , Quast Günter , Reussner Ralf , Stemmer-Grabow Maximilian 
Published: September 2019

The amount of data to be processed by experiments in high energy physics (HEP) will increase tremendously in the coming years. To cope with this increasing load, most efficient usage of the resources is mandatory. Furthermore, the computing resources for user jobs in HEP will be increasingly distributed and heterogeneous, resulting in more difficult scheduling due to the increasing complexity of the system. We aim to create a simulation for the WLCG helping the HEP community to solve both challenges: a more efficient utilization of the grid and coping with the rising complexity of the system. There is currently no simulation in existence which helps the operators of the grid to make the correct decisions while optimizing the load balancing strategy. This paper presents a proof of concept in which the computing jobs at the Tier 1 center GridKa are modeled and simulated. To model the computing jobs we extended the Palladio simulator with a mechanism to simulate load balancing strategies. Furthermore, we implemented an automated model parameter analysis and model creation.
Finally, the simulation results are validated using real-word performance data. Our results suggest that simulating larger parts of the grid is feasible and can help to optimize the utilization of the grid.
Capability-Based Authorization for HEP
Authors: Weitzel Derek , Bockelman Brian , Basney Jim , Tannenbaum Todd , Miller Zach , Gaynor Jeff 
Published: September 2019

Outside the HEP computing ecosystem, it is vanishingly rare to encounter user X509 certificate authentication (and proxy certificates are even more rare). The web never widely adopted the user certificate model, but increasingly sees the need for federated identity services and distributed authorization. For example, Dropbox, Google and Box instead use bearer tokens issued via the OAuth2 protocol to authorize actions on their services. Thus, the HEP ecosystem has the opportunity to reuse recent work in industry that now covers our needs. We present a token-based ecosystem for authorization tailored for use by CMS.
We base the tokens on the SciTokens profile for the standardized JSON Web Token (JWT) format. The token embeds a signed description of what capabilities the VO grants the bearer; the site-level service can verify the VO’s signature without contacting a central service.
In this paper, we describe the modifications done to enable token-based authorization in various software packages used by CMS, including XRootD, CVMFS, and HTCondor. We describe the token-issuing workflows that would be used to get tokens to running jobs in order to authorize data access and file stageout, and explain the advantages for hosted web services. Finally, we outline what the transition would look like for an experiment like CMS.