bluuebunny/crossref_metadata_2025_split huggingface dataset:
The expression patterns and the diagnostic/prognostic roles of PTPN family members in digestive tract cancers
Authors: Chen Jing , Zhao Xu , Yuan Yuan , Jing Jing-Jing 
Published: June 2020

AbstractBackgroundNon-receptor protein tyrosine phosphatases (PTPNs) are a set of enzymes involved in the tyrosyl phosphorylation. The present study intended to clarify the associations between the expression patterns of PTPN family members, and diagnosis as well as the prognosis of digestive tract cancers.MethodsOncomine and Ualcan were used to analyze PTPN expressions. Data from The Cancer Genome Atlas (TCGA) were downloaded through UCSC Xena for validation and to explore the relationship of the PTPN expression with diagnosis, clinicopathological parameters and survival of digestive tract cancers. Gene ontology enrichment analysis was conducted using the DAVID database. The gene–gene interaction network was performed by GeneMANIA and the protein–protein interaction (PPI) network was built using STRING portal coupled with Cytoscape. The expression of differentially expressed PTPNs in cancer cell lines were explored using CCLE. Moreover, by histological verification, the expression of four PTPNs in digestive tract cancers were further analyzed.ResultsMost PTPN family members were associated with digestive tract cancers according to Oncomine, Ualcan and TCGA data. Several PTPN members were differentially expressed in digestive tract cancers. For esophageal carcinoma (ESCA), PTPN1 and PTPN12 levels were correlated with incidence; PTPN20 was associated with poor prognosis. For stomach adenocarcinoma (STAD), PTPN2 and PTPN12 levels were correlated with incidence; PTPN3, PTPN5, PTPN7, PTPN11, PTPN13, PTPN14, PTPN18 and PTPN23 were correlated with pathological grade; PTPN20 expression was related with both TNM stage and N stage; PTPN22 was associated with T stage and pathological grade; decreased expression of PTPN5 and PTPN13 implied worse overall survival of STAD, while elevated PTPN6 expression indicated better prognosis. For colorectal cancer (CRC), PTPN2, PTPN21 and PTPN22 levels were correlated with incidence; expression of PTPN5, PTPN12, and PTPN14 was correlated with TNM stage and N stage; high PTPN5 or PTPN7 expression was associated with increased hazards of death. CCLE analyses showed that in esophagus cancer cell lines, PTPN1, PTPN4 and PTPN12 were highly expressed; in gastric cancer cell lines, PTPN2 and PTPN12 were highly expressed; in colorectal cancer cell lines, PTPN12 was highly expressed while PTPN22 was downregulated. Results of histological verification experiment showed differential expressions of PTPN22 in CRC, and PTPN12 in GC and CRC.ConclusionsMembers of PTPN family were differentially expressed in digestive tract cancers. Correlations were found between PTPN genes and clinicopathological parameters of patients. Expression of PTPN12 was upregulated in both STAD and CRC, and thus could be used as a diagnostic biomarker. Differential expression of PTPN12 in GC and CRC, and PTPN22 in CRC were presented in our histological verification experiment.
Myocarditis successfully diagnosed and controlled with speckle tracking echocardiography
Authors: Uziębło-Życzkowska Beata , Mielniczuk Marta , Ryczek Robert , Krzesiński Paweł 
Published: June 2020

Abstract
Background
Speckle tracking echocardiography (STE) is an objective, well-validated and reproducible technique of assessing left ventricular longitudinal deformation; it also offers a more sensitive assessment of myocardial contractility than widely used visual estimation. Evaluating global longitudinal strain may help identify patients with subclinical left ventricular systolic dysfunction.

Case presentation
We report the case of a 28-year-old man with myocarditis, which successfully diagnosed and followed-up with the novel echocardiography method using speckle tracking imaging. The patient was referred to our hospital with an initial diagnosis of ST-segment elevation myocardial infarction. Transthoracic echocardiography did not show any contractility abnormalities. Hence, in the course of further diagnostics, left ventricular function was assessed by STE. Depressed global longitudinal strain was noted within several segments of the left ventricle. Then, cardiac magnetic resonance imaging was performed to confirm the diagnosis of myocarditis.

Conclusions
STE seems to be competitive in relation to cardiac magnetic resonance imaging in the diagnosis of some diseases, such as myocarditis.
Human induced pluripotent stem cell line banking for the production of rare blood type erythrocytes
Authors: Park Yu Jin , Jeon Su-Hee , Kim Hyun-Kyung , Suh Eun Jung , Choi Seung Jun , Kim Sinyoung , Kim Hyun Ok 
Published: June 2020

Abstract
Background
The in vitro production of mature human red blood cells (RBCs) from induced pluripotent stem cells (iPSCs) has been the focus of research to meet the high demand for blood transfusions. However, limitations like high costs and technological requirements restrict the use of RBCs produced by iPSC differentiation to specific circumstances, such as for patients with rare blood types or alloimmunized patients. In this study, we developed a detailed protocol for the generation of iPSC lines derived from peripheral blood of donors with O D-positive blood and rare blood types (D–and Jr(a-)) and subsequent erythroid differentiation.

Methods
Mononuclear cells separated from the peripheral blood of O D-positive and rare blood type donors were cultured to produce and expand erythroid progenitors and reprogrammed into iPSCs. A 31-day serum-free, xeno-free erythroid differentiation protocol was used to generate reticulocytes. The stability of iPSC lines was confirmed with chromosomal analysis and RT-PCR. Morphology and cell counts were determined by microscopy observations and flow cytometry.

Results
Cells from all donors were successfully used to generate iPSC lines, which were differentiated into erythroid precursors without any apparent chromosomal mutations. This differentiation protocol resulted in moderate erythrocyte yield per iPSC.

Conclusions
It has previously only been hypothesized that erythroid differentiation from iPSCs could be used to produce RBCs for transfusion to patients with rare blood types or who have been alloimmunized. Our results demonstrate the feasibility of producing autologous iPSC-differentiated RBCs for clinical transfusions in patients without alternative options.
Myelination- and immune-mediated MR-based brain network correlates
Authors: Cerina Manuela , Muthuraman Muthuraman , Gallus Marco , Koirala Nabin , Dik Andre , Wachsmuth Lydia , Hundehege Petra , Schiffler Patrick , Tenberge Jan-Gerd , Fleischer Vinzenz , Gonzalez-Escamilla Gabriel , Narayanan Venu , Krämer Julia , Faber Cornelius , Budde Thomas , Groppa Sergiu , Meuth Sven G. 
Published: June 2020

Abstract
Background
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by inflammatory and neurodegenerative processes. Despite demyelination being a hallmark of the disease, how it relates to neurodegeneration has still not been completely unraveled, and research is still ongoing into how these processes can be tracked non-invasively. Magnetic resonance imaging (MRI) derived brain network characteristics, which closely mirror disease processes and relate to functional impairment, recently became important variables for characterizing immune-mediated neurodegeneration; however, their histopathological basis remains unclear.

Methods
In order to determine the MRI-derived correlates of myelin dynamics and to test if brain network characteristics derived from diffusion tensor imaging reflect microstructural tissue reorganization, we took advantage of the cuprizone model of general demyelination in mice and performed longitudinal histological and imaging analyses with behavioral tests. By introducing cuprizone into the diet, we induced targeted and consistent demyelination of oligodendrocytes, over a period of 5 weeks. Subsequent myelin synthesis was enabled by reintroduction of normal food.

Results
Using specific immune-histological markers, we demonstrated that 2 weeks of cuprizone diet induced a 52% reduction of myelin content in the corpus callosum (CC) and a 35% reduction in the neocortex. An extended cuprizone diet increased myelin loss in the CC, while remyelination commenced in the neocortex. These histologically determined dynamics were reflected by MRI measurements from diffusion tensor imaging. Demyelination was associated with decreased fractional anisotropy (FA) values and increased modularity and clustering at the network level. MRI-derived modularization of the brain network and FA reduction in key anatomical regions, including the hippocampus, thalamus, and analyzed cortical areas, were closely related to impaired memory function and anxiety-like behavior.

Conclusion
Network-specific remyelination, shown by histology and MRI metrics, determined amelioration of functional performance and neuropsychiatric symptoms. Taken together, we illustrate the histological basis for the MRI-driven network responses to demyelination, where increased modularity leads to evolving damage and abnormal behavior in MS. Quantitative information about in vivo myelination processes is mirrored by diffusion-based imaging of microstructural integrity and network characteristics.
Influenza a virus antagonizes type I and type II interferon responses via SOCS1-dependent ubiquitination and degradation of JAK1
Authors: Du Yinping , Yang Fan , Wang Qiuxia , Xu Nuo , Xie Yizhang , Chen Sujuan , Qin Tao , Peng Daxin 
Published: June 2020

Abstract
Background
Although influenza A virus (IAV) employs diverse strategies to evade IFN responses by inhibiting the synthesis of IFN, how IAV regulates signaling downstream of IFN is incompletely understood.

Methods
In this study, we used Western blot-based protein analysis coupled with RT-qPCR, overexpression and RNA interference to investigate the regulation of JAK1 by IAV infection.

Results
The results indicated that JAK1 was ubiquitinated and degraded, resulting in inhibition of type I and type II IFN responses, demonstrating that IAV antagonizes the IFN-activated JAK/STAT signaling pathway by inducing the degradation of JAK1. Furthermore. IAV infection upregulated the suppressor of cytokine signaling (SOCS) protein SOCS1, and SOCS1 mediated the ubiquitination and degradation of JAK1.

Conclusion
Collectively, our findings suggest that IAV infection induces SOCS1 expression to promote JAK1 degradation, which in turn inhibits host innate immune responses.
Reliability of ITV approach to varying treatment fraction time: a retrospective analysis based on 2D cine MR images
Authors: Cusumano Davide , Dhont Jennifer , Boldrini Luca , Chiloiro Giuditta , Romano Angela , Votta Claudio , Longo Silvia , Placidi Lorenzo , Azario Luigi , De Spirito Marco , Verellen Dirk , Valentini Vincenzo 
Published: June 2020

Abstract
Background
Internal Target Volume (ITV) is one of the most common strategies to passively manage tumour motion in Radiotherapy (RT).
The reliability of this approach is based on the assumption that the tumour motion estimated during pre-treatment 4D Computed Tomography (CT) acquisition is representative of the motion during the whole RT treatment. With the introduction of Magnetic Resonance-guided RT (MRgRT), it has become possible to monitor tumour motion during the treatment and verify this assumption.
Aim of this study was to investigate the reliability of the ITV approach with respect to the treatment fraction time (TFT) in abdominal and thoracic lesions.

Methods
A total of 12 thoracic and 15 abdominal lesions was analysed. Before treatment, a 10-phase 4DCT was acquired and ITV margins were estimated considering the envelope of the lesion contoured on the different 4DCT phases.
All patients underwent MRgRT treatment in free-breathing, monitoring the tumour position on a sagittal plane with 4 frames per second (sec). ITV margins were projected on the tumour trajectory and the percentage of treatment time in which the tumour was inside the ITV (%TT) was measured to varying of TFT.
The ITV approach was considered moderately reliable when %TT ≥ 90% and strongly reliable when %TT ≥ 95%. Additional ITV margins required to achieve %TT ≥ 95% were also calculated.

Results
In the analysed cohort of patients, ITV strategy can be considered strongly reliable only for lung lesions with TFT ≤ 7 min (min). The ITV strategy can be considered only moderately reliable for abdominal lesions, and additional margins are required to obtain %TT ≥ 95%.
Considering a TFT ≤ 4 min, additional margins of 2 mm in cranio-caudal (CC) and 1 mm in antero-posterior (AP) are suggested for pancreatic lesions, 3 mm in CC and 2 mm in AP for renal and liver ones.

Conclusions
On the basis of the analysed cases, the ITV approach appears to be reliable in the thorax, while it results more challenging in the abdomen, due to the higher uncertainty in ITV definition and to the observed larger intra and inter-fraction motion variability. The addition of extra margins based on the TFT may represent a valid tool to compensate such limitations.
Mechanism of Dayuanyin in the treatment of coronavirus disease 2019 based on network pharmacology and molecular docking
Authors: Ruan Xiaofeng , Du Peng , Zhao Kang , Huang Jucun , Xia Hongmei , Dai Dan , Huang Shu , Cui Xiang , Liu Liming , Zhang Jianjun 
Published: June 2020

Abstract
Background
At present, coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, is spreading all over the world, with disastrous consequences for people of all countries. The traditional Chinese medicine prescription Dayuanyin (DYY), a classic prescription for the treatment of plague, has shown significant effects in the treatment of COVID-19. However, its specific mechanism of action has not yet been clarified. This study aims to explore the mechanism of action of DYY in the treatment of COVID-19 with the hope of providing a theoretical basis for its clinical application.

Methods
First, the TCMSP database was searched to screen the active ingredients and corresponding target genes of the DYY prescription and to further identify the core compounds in the active ingredient. Simultaneously, the Genecards database was searched to identify targets related to COVID-19. Then, the STRING database was applied to analyse protein–protein interaction, and Cytoscape software was used to draw a network diagram. The R language and DAVID database were used to analyse GO biological processes and KEGG pathway enrichment. Second, AutoDock Vina and other software were used for molecular docking of core targets and core compounds. Finally, before and after application of DYY, the core target gene IL6 of COVID-19 patients was detected by ELISA to validate the clinical effects.

Results
First, 174 compounds, 7053 target genes of DYY and 251 genes related to COVID-19 were selected, among which there were 45 target genes of DYY associated with treatment of COVID-19. This study demonstrated that the use of DYY in the treatment of COVID-19 involved a variety of biological processes, and DYY acted on key targets such as IL6, ILIB, and CCL2 through signaling pathways such as the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and cytokine–cytokine receptor interaction. DYY might play a vital role in treating COVID-19 by suppressing the inflammatory storm and regulating immune function. Second, the molecular docking results showed that there was a certain affinity between the core compounds (kaempferol, quercetin, 7-Methoxy-2-methyl isoflavone, naringenin, formononetin) and core target genes (IL6, IL1B, CCL2). Finally, clinical studies showed that the level of IL6 was elevated in COVID-19 patients, and DYY can reduce its levels.

Conclusions
DYY may treat COVID-19 through multiple targets, multiple channels, and multiple pathways and is worthy of clinical application and promotion.
SURF: integrative analysis of a compendium of RNA-seq and CLIP-seq datasets highlights complex governing of alternative transcriptional regulation by RNA-binding proteins
Authors: Chen Fan , Keleş Sündüz 
Published: June 2020

AbstractAdvances in high-throughput profiling of RNA-binding proteins (RBPs) have resulted inCLIP-seq datasets coupled with transcriptome profiling by RNA-seq. However, analysis methods that integrate both types of data are lacking. We describe SURF, Statistical Utility for RBP Functions, for integrative analysis of large collections of CLIP-seq and RNA-seq data. We demonstrate SURF’s ability to accurately detect differential alternative transcriptional regulation events and associate them to local protein-RNA interactions. We apply SURF to ENCODE RBP compendium and carry out downstream analysis with additional reference datasets. The results of this application are browsable athttp://www.statlab.wisc.edu/shiny/surf/.
Corneal cross-linking versus standard care in children with keratoconus – a randomised, multicentre, observer-masked trial of efficacy and safety (KERALINK): a statistical analysis plan
Authors: Chowdhury Kashfia , Doré Caroline J. , Bunce Catey , Larkin Daniel F. P. 
Published: June 2020

Abstract
Background
The KERALINK trial tests the hypothesis that corneal cross-linking (CXL) treatment reduces the progression of keratoconus in comparison to standard care in patients aged 10–16 years. This article describes the statistical analysis plan for this trial as an update to the published protocol. It is written before the end of the patient follow-up, while the outcome of the trial is still unknown.

Design and methods
KERALINK is a randomised controlled, observer-masked, multicentre trial in progressive keratoconus comparing epithelium-off CXL with standard care, including spectacles or contact lenses as necessary for best-corrected acuity. Keratoconus is a disorder of the shape of the cornea in which the normally round dome-shaped clear front window of the eye (cornea) thins progressively leading to a cone-like bulge. This impairs the ability of the eye to focus properly, causing reduced vision which requires spectacle or contact lens wear or, in a minority of patients, eventually corneal replacement by a transplant for best vision. The primary outcome measure is the between-group difference in K2 at 18 months adjusted for K2 at baseline examination. K2 is the value of the steepest corneal meridian as measured on Pentacam topography. Secondary outcomes are keratoconus progression, time to keratoconus progression, visual acuity, refraction, apical corneal thickness and adverse events. Patient-reported effects will be explored by questionnaires. We describe in detail the statistical aspects of KERALINK: the outcome measures, the sample size calculation, general analysis principles, the planned descriptive statistics and statistical models, and planned subgroup and sensitivity analyses.

Discussion
The KERALINK statistical analysis will provide comprehensive and precise information on the relative effectiveness of the two treatments. The plan will be implemented in May 2020 when follow-up for the trial is completed.

Trial registration
EudraCT, 2016-001460-11. Registered on 19 May 2016.
Pan-American Trypanosoma (Megatrypanum) trinaperronei n. sp. in the white-tailed deer Odocoileus virginianus Zimmermann and its deer ked Lipoptena mazamae Rondani, 1878: morphological, developmental and phylogeographical characterisation
Authors: Garcia Herakles A. , Blanco Pilar A. , Rodrigues Adriana C. , Rodrigues Carla M. F. , Takata Carmen S. A. , Campaner Marta , Camargo Erney P. , Teixeira Marta M. G. 
Published: June 2020

Abstract
Background
The subgenus Megatrypanum Hoare, 1964 of Trypanosoma Gruby, 1843 comprises trypanosomes of cervids and bovids from around the world. Here, the white-tailed deer Odocoileus virginianus (Zimmermann) and its ectoparasite, the deer ked Lipoptena mazamae Rondani, 1878 (hippoboscid fly), were surveyed for trypanosomes in Venezuela.

Results
Haemoculturing unveiled 20% infected WTD, while 47% (7/15) of blood samples and 38% (11/29) of ked guts tested positive for the Megatrypanum-specific TthCATL-PCR. CATL and SSU rRNA sequences uncovered a single species of trypanosome. Phylogeny based on SSU rRNA and gGAPDH sequences tightly cluster WTD trypanosomes from Venezuela and the USA, which were strongly supported as geographical variants of the herein described Trypanosoma (Megatrypanum) trinaperronei n. sp. In our analyses, the new species was closest to Trypanosoma sp. D30 from fallow deer (Germany), both nested into TthII alongside other trypanosomes from cervids (North American elk and European fallow, red and sika deer), and bovids (cattle, antelopes and sheep). Insights into the life-cycle of T. trinaperronei n. sp. were obtained from early haemocultures of deer blood and co-culture with mammalian and insect cells showing flagellates resembling Megatrypanum trypanosomes previously reported in deer blood, and deer ked guts. For the first time, a trypanosome from a cervid was cultured and phylogenetically and morphologically (light and electron microscopy) characterised.

Conclusions
In the analyses based on SSU rRNA, gGAPDH, CATL and ITS rDNA sequences, neither cervids nor bovids trypanosomes were monophyletic but intertwined within TthI and TthII major phylogenetic lineages. One host species can harbour more than one species/genotype of trypanosome, but each trypanosome species/genotype was found in a single host species or in phylogenetically closely related hosts. Molecular evidence that L. mazamae may transmit T. trinaperronei n. sp. suggests important evolutionary constraints making tight the tripartite T. trinaperronei-WTD-deer ked association. In a plausible evolutionary scenario, T. trinaperronei n. sp. entered South America with North American white-tailed deer at the Pliocene-Pleistocene boundary following the closure of the Panama Isthmus.