bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of PKCε in the epithelial-mesenchymal transition induced by FGFR2 isoform switch
Authors: Ranieri Danilo , Nanni Monica , Persechino Flavia , Torrisi Maria Rosaria , Belleudi Francesca 
Published: May 2020

AbstractBackgroundThe epithelial isoform of the fibroblast growth factor receptor 2 (FGFR2b) controls the entire program of keratinocyte differentiation via the sequential involvement of protein kinase C (PKC) δ and PKCα. In contrast, the FGFR2 isoform switch and the aberrant expression of the mesenchymal FGFR2c isoform leads to impairment of differentiation, epithelial-mesenchymal transition (EMT) and tumorigenic features. Aim of our present study was to contribute in clarifying the complex network of signaling pathways involved in the FGFR2c-mediated oncogenic outcomes focusing on PKCε, which appears to be involved in the induction of EMT and tumorigenesis in several epithelial contexts.MethodsBiochemical and molecular analysis, as well as in vitro invasion assays, combined with the use of specific small interfering RNA (siRNA), were performed in human keratinocytes stably expressing FGFR2c or FGFR2b isoforms.ResultsOur results showed that aberrant expression and signaling of FGFR2c, but not those of FGFR2b, in human keratinocytes induced a strong phosphorylation/activation of PKCε. The use of siRNA approach showed that PKCε is the hub signaling downstream FGFR2c responsible for the modulation of EMT markers and for the induction of the EMT-related transcription factors STAT3, Snail1 and FRA1, as well as for the acquisition of the invasive behavior. Moreover, experiments of depletion of ESRP1, responsible for FGFR2 splicing in epithelial cells, indicated that the activation of PKCε is the key molecular event triggered by FGFR2 isoform switch and underlying EMT induction.ConclusionsOverall, our results point to the identification of the downstream PKC isoform responsible for the FGFR signaling deregulation occurring in epithelial tissues from the physiological oncosoppressive to the pathological oncogenic profile.Graphical abstract
The urgent need for integrated science to fight COVID-19 pandemic and beyond
Authors: Moradian Negar , Ochs Hans D. , Sedikies Constantine , Hamblin Michael R. , Camargo Carlos A. , Martinez J. Alfredo , Biamonte Jacob D. , Abdollahi Mohammad , Torres Pedro J. , Nieto Juan J. , Ogino Shuji , Seymour John F. , Abraham Ajith , Cauda Valentina , Gupta Sudhir , Ramakrishna Seeram , Sellke Frank W. , Sorooshian Armin , Wallace Hayes A. , Martinez-Urbistondo Maria , Gupta Manoj , Azadbakht Leila , Esmaillzadeh Ahmad , Kelishadi Roya , Esteghamati Alireza , Emam-Djomeh Zahra , Majdzadeh Reza , Palit Partha , Badali Hamid , Rao Idupulapati , Saboury Ali Akbar , Jagan Mohan Rao L. , Ahmadieh Hamid , Montazeri Ali , Fadini Gian Paolo , Pauly Daniel , Thomas Sabu , Moosavi-Movahed Ali A. , Aghamohammadi Asghar , Behmanesh Mehrdad , Rahimi-Movaghar Vafa , Ghavami Saeid , Mehran Roxana , Uddin Lucina Q. , Von Herrath Matthias , Mobasher Bahram , Rezaei Nima 
Published: May 2020

AbstractThe COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world’s scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic’s consequences and prevent recurrences of similar pandemics.
Diffusion tensor imaging point to ongoing functional impairment in HIV-infected children at age 5, undetectable using standard neurodevelopmental assessments
Authors: Ackermann Christelle , Andronikou Savvas , Saleh Muhammad G. , Kidd Martin , Cotton Mark F. , Meintjes Ernesta M. , Laughton Barbara 
Published: May 2020

Abstract
Background
Perinatal HIV infection negatively impacts cognitive functioning of children, main domains affected are working memory, processing speed and executive function. Early ART, even when interrupted, improves neurodevelopmental outcomes. Diffusion tension imaging (DTI) is a sensitive tool assessing white matter damage. We hypothesised that white matter measures in regions showing HIV-related alterations will be associated with lower neurodevelopmental scores in specific domains related to the functionality of the affected tracts.

Methods
DTI was performed on children in a neurodevelopmental sub study from the Children with HIV Early Antiretroviral (CHER) trial. Voxel-based group comparisons to determine regions where fractional anisotropy and mean diffusion differed between HIV+ and uninfected children were done. Locations of clusters showing group differences were identified using the Harvard–Oxford cortical and subcortical and John Hopkins University WM tractography atlases provided in FSL. This is a second review of DTI data in this cohort, which was reported in a previous study. Neurodevelopmental assessments including GMDS and Beery-Buktenica tests were performed and correlated with DTI parameters in abnormal white matter.

Results
38 HIV+ children (14 male, mean age 64.7 months) and 11 controls (4 male, mean age 67.7 months) were imaged. Two clusters with lower fractional anisotropy and 7 clusters with increased mean diffusion were identified in the HIV+ group. The only neurodevelopmental domain with a trend of difference between the HIV+ children and controls (p = 0.08), was Personal Social Quotient which correlated to improved myelination of the forceps minor in the control group. As a combined group there was a negative correlation between visual perception and radial diffusion in the right superior longitudinal fasciculus and left inferior longitudinal fasciculus, which may be related to the fact that these tracts, forming part of the visual perception pathway, are at a crucial state of development at age 5.

Conclusion
Even directed neurodevelopmental tests will underestimate the degree of microstructural white matter damage detected by DTI. The visual perception deficit detected in the entire study population should be further examined in a larger study.
Heterologous prime-boost: an important candidate immunization strategy against Tembusu virus
Authors: Pan Yuting , Jia Renyong , Li Juping , Wang Mingshu , Chen Shun , Liu Mafeng , Zhu Dekang , Zhao Xinxin , Wu Ying , Yang Qiao , Yin Zhongqiong , Jing Bo , Huang Juan , Zhang Shaqiu , Zhang Lin , Liu Yunya , Yu Yanlin , Tian Bin , Pan Leichang , Rehman Mujeeb Ur , Cheng Anchun 
Published: May 2020

Abstract
Background
Tembusu virus (TMUV), a newly emerging pathogenic flavivirus, spreads rapidly between ducks, causing massive economic losses in the Chinese duck industry. Vaccination is the most effective method to prevent TMUV. Therefore, it is urgent to look for an effective vaccine strategy against TMUV. Heterologous prime-boost regimens priming with vaccines and boosting with recombinant adenovirus vaccines have been proven to be successful strategies for protecting against viruses in experimental animal models.

Methods
In this study, heterologous and homologous prime-boost strategies using an attenuated salmonella vaccine and a recombinant adenovirus vaccine expressing prM-E or the E gene of TMUV were evaluated to protect ducks against TMUV infection for the first time, including priming and boosting with the attenuated salmonella vaccine, priming and boosting with the recombinant adenovirus vaccine, and priming with the attenuated salmonella vaccine and boosting with the recombinant adenovirus vaccine. Humoral and cellular immune responses were detected and evaluated. We then challenged the ducks with TMUV at 12 days after boosting to assay for clinical symptoms, mortality, viral loads and histopathological lesions after these different strategies.

Results
Compared with the homologous prime-boost strategies, the heterologous prime-boost regimen produced higher levels of neutralizing antibodies and IgG antibodies against TMUV. Additionally, it could induce higher levels of IFN-γ than homologous prime-boost strategies in the later stage. Interestingly, the heterologous prime-boost strategy induced higher levels of IL-4 in the early stage, but the IL-4 levels gradually decreased and were even lower than those induced by the homologous prime-boost strategy in the later stage. Moreover, the heterologous prime-boost strategy could efficiently protect ducks, with low viral titres, no clinical symptoms and histopathological lesions in this experiment after challenge with TMUV, while slight clinical symptoms and histopathological lesions were observed with the homologous prime-boost strategies.

Conclusions
Our results indicated that the heterologous prime-boost strategy induced higher levels of humoral and cellular immune responses and better protection against TMUV infection in ducks than the homologous prime-boost strategies, suggesting that the heterologous prime-boost strategy is an important candidate for the design of a novel vaccine strategy against TMUV.
Host shutoff activity of VHS and SOX-like proteins: role in viral survival and immune evasion
Authors: He Tianqiong , Wang Mingshu , Cheng Anchun , Yang Qiao , Wu Ying , Jia Renyong , Liu Mafeng , Zhu Dekang , Chen Shun , Zhang Shaqiu , Zhao Xin-Xin , Huang Juan , Sun Di , Mao Sai , Ou Xuming , Wang Yin , Xu Zhiwen , Chen Zhengli , Zhu Lin , Luo Qihui , Liu Yunya , Yu Yanling , Zhang Ling , Tian Bin , Pan Leichang , Rehman Mujeeb Ur , Chen Xiaoyue 
Published: May 2020

Abstract
Background
Host shutoff refers to the widespread downregulation of host gene expression and has emerged as a key process that facilitates the reallocation of cellular resources for viral replication and evasion of host antiviral immune responses.

Main body
The Herpesviridae family uses a number of proteins that are responsible for host shutoff by directly targeting messenger RNA (mRNA), including virion host shutoff (VHS) protein and the immediate-early regulatory protein ICP27 of herpes simplex virus types 1 (HSV-1) and the SOX (shutoff and exonuclease) protein and its homologs in Gammaherpesvirinae subfamilies, although these proteins are not homologous. In this review, we highlight evidence that host shutoff is promoted by the VHS, ICP27 and SOX-like proteins and that they also contribute to immune evasion.

Conclusions
Further studies regarding the host shutoff proteins will not only contribute to provide new insights into the viral replication, expression and host immune evasion process, but also provide new molecular targets for the development of antiviral drugs and therapies.
Recording of cardiovascular risk factors by general practitioners in patients with schizophrenia
Authors: Castillejos Mª Carmen , Martín-Pérez Carlos , García-Ruiz Antonio , Mayoral-Cleries Fermín , Moreno-Küstner Berta 
Published: May 2020

Abstract
Background
Patients with schizophrenia and related disorders (SRD) are more predisposed to having cardiovascular risk factors (CVRFs) compared to the general population due to a combination of lifestyle factors and exposure to antipsychotic medications. We aimed to analyse the documentation practices of CVRFs by general practitioners (GPs) and its associations with patient variables in a sample of persons with SRD.

Methods
An observational, cross-sectional study was conducted in 13 primary care centres (PCCs) in Malaga (Spain). The population comprised all patients with SRD who were in contact with a GP residing in the study area. The number of CVRFs (type 2 diabetes mellitus, hypertension, hypercholesterolaemia, obesity and smoking) recorded by GPs were analysed by considering patients’ demographic and clinical variables and use of primary care services. We performed descriptive, bivariate and multivariate regression analyses.

Results
A total of 494 patients were included; CVRFs were not recorded in 59.7% of the patients. One CVRF was recorded in 42.1% of patients and two or more CVRFs were recorded in 16.1% of patients. Older age, living in an urban area and a higher number of visits to the GP were associated with a higher number of CVRFs recorded.

Conclusion
The main finding in this study is that both patients’ demographic variables as well as use of primary care services were found to be related to the documentation of CVRFs in patients with SRD by GPs.
Do working characteristics influence the participation at health measures? Findings from a trial phase of workplace health promotion
Authors: Reinhardt Annika , Adams Johanna , Schöne Klaus , Rose Dirk-Matthias , Sammito Stefan 
Published: May 2020

Abstract
Background
Health behavior is presumed to be influenced by organizational factors. This study analyzes how workplace characteristics influence health behavior in terms of participation at health measures.

Methods
Employees of the German Federal Ministry of Defense were surveyed at the beginning (January / February 2015) and at the end (June 2015) of the trial phase of workplace health promotion (WHP). Differences in participation of characteristic groups were calculated using Pearson’s Chi2-Test and T-Test, chances of participation were estimated using multilevel logistic regression.

Results
Employees who reported higher satisfaction with work demand participated more often in health measures (aOR: 1.02, 95%-CI = 1.01, 1.04, p < 0.001). Large amount of variance in participation can be attributed to department level.

Conclusion
Participation at WHP varies significantly between settings after controlling for individuals’ characteristics. Thus, working characteristics should be considered as a decisive factor for WHP effectiveness. There is consensus that behavioral prevention is most effective when conditional prevention is granted as behavior is presumed to be influenced by individuals´ environmental conditions. Though objective working conditions may seem similar further context characteristics which remain unconsidered may lead to different behavior patterns. This article shows that more attention must be payed to setting specific characteristics with regard to effective Occupational Health Promotion.
This project is registered by the Federal Ministry of Defense (research number: E/U2AD/ED003/EF555).
The riddle of shiftwork and disturbed chronobiology: a case study of landmark smoking data demonstrates fallacies of not considering the ubiquity of an exposure
Authors: Erren Thomas C. , Lewis Philip , Morfeld Peter 
Published: May 2020

Abstract
Background
Failing to integrate all sources of a ubiquitous hazard candidate may explain inconsistent and/or null, and overall misleading, results in epidemiological studies such as those related to shift-work.

Methods
We explore this rationale on the assumption that Doll and Hill had confined their 1950 landmark study to smoking at workplaces alone. We assess how non-differential, or how differential, underestimation of exposure could have biased computed risks.

Results
Systematically unappreciated exposures at play could have led to substantial information bias. Beyond affecting the magnitude of risks, not even the direction of risk distortion would have been predictable.

Conclusions
Disturbed chronobiology research should consider cumulative doses from all walks of life. This is a conditiosine qua non to avoid potentially biased and uninterpretable risk estimates when assessing effects of a ubiquitous hazard candidate.
Gli1 regulates stemness characteristics in gastric adenocarcinoma
Authors: Qi Wenbo , Yang Zhaoting , Feng Ying , Li Haoyue , Che Nan , Liu Lan , Xuan Yanhua 
Published: May 2020

Abstract
Background
Glioma-associated oncogene homolog 1 (Gli1), affects the progression and the stemness characteristics of malignant carcinoma. The aim of the present study was to identify the relation between Glioma-associated oncogene homolog 1 (Gli1) and stemness and determine its clinical significance in gastric adenocarcinoma (GA). We investigated Gli1 expression and its correlation with other stemness-associated proteins in 169 GA samples and 5 GA cell lines.

Methods
To elucidate the role of Gli1 in the clinicopathological significance and stemness of GA, tissues samples from 169 GA patients were collected for immunohistochemistry (IHC). Additionally, MKN74, MKN28, NCI-N87, SNU638, AGS cells were collected for western blotting, MKN28 cells were collected for spheroid formation assay.

Results
Results showed that Gli1 expression was closely related to tumor grade, primary tumor (pT) stage, distant metastasis, clinical stage, gross type, microvessel density, and shorter overall survival (OS). Cox regression analysis verified that Gli1 was an independent prognostic factor for OS. Furthermore, Gli1 expression correlated with the expression of stemness-related genes, CD44, LSD1, and Sox9. Gli1 inhibitor GANT61 significantly decreased the expression of CD44 and LSD1, and spheroid formation ability of the MKN28 cells.

Conclusions
In conclusion, Gli1 may be a poor prognostic indicator and a potential cancer stemness-related protein in GA.
Primary sarcoma of the heart: case report and literature review
Authors: Moeri-Schimmel Rieneke , Pras Elisabeth , Desar Ingrid , Krol Stijn , Braam Pètra 
Published: May 2020

Abstract
Background
Primary cardiac tumors are extremely rare. Most primary cardiac tumors are benign and around one quarter is malign. Sarcomas are accounting for 95% of these malign tumors and they show different histologies. The prognosis is poor with a mean survival of 3 months to 1 year, even with complete radical resection. We report the cases of two patients with primary cardiac sarcoma treated with surgery and radiation and/or chemotherapy. In addition we retrospectively collected data of patients with primary cardiac sarcoma treated between 2005 and 2019 with minimum follow-up of 12 months. Clinical characteristics, treatment modalities and outcomes were collected and analyzed. Finally a literature review was done.

Case presentation
The first patient presented with cerebellar infarction. When she developed a recurrence analysis showed a suspicious myocardial lesion for which irradical surgery (R2) was performed. Histopathology showed an intimal sarcoma of the left atrium. Postoperative radiotherapy was applied without complications. Three months after treatment multiple metastases were diagnosed and she died 13 months after initial diagnosis. The second patient presented with pericardial effusion. A tumor was found located in the right atrium and radical surgery was performed. Histopathology showed an angiosarcoma, without signs of metastases. Adjuvant radiotherapy was added because of close margins and based on high risk of recurrence and metastases it was decided to add chemotherapy. One year after finishing treatment, evaluation showed local recurrence together with pulmonary metastases.

Conclusions
Surgery combined with postoperative radiotherapy is feasible in patients with resectable cardiac sarcoma. Distant metastases occur frequently. In patients with an irresectable sarcoma of the heart primary radiotherapy should be considered.
Potential therapeutic effect of Qingwen Baidu Decoction against Corona Virus Disease 2019: a mini review
Authors: Wen Jianxia , Wang Ruilin , Liu Honghong , Tong Yuling , Wei Shizhang , Zhou Xuelin , Li Haotian , Jing Manyi , Wang Min , Zhao Yanling 
Published: May 2020

AbstractThe Corona Virus Disease 2019 (COVID-19) is an acute respiratory infectious disease. At present, COVID-19 has no specific therapeutic drugs, and the main clinical treatment is symptomatic treatment and control of complications. On March 5, 2020, the National Health Commission of the People’s Republic of China issued the Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Infection (Trial Version 7), which integrated traditional Chinese medicine (TCM) into the treatment of COVID-19. The purpose of this study is to summarize recent studies on the clinic application, pharmacological action, chemical substances and mechanism of Qingwen Baidu Decoction (QBD) on the treatment of various diseases. The results suggested that QBD has multiple pharmacological effects such as anti-inflammation, antiviral, antibacterial, immunomodulatory, antipyretic and so on. It has been used in the treatment of sepsis, epidemic hemorrhagic fever, epidemic cerebrospinal meningitis, infantile pneumonia, sepsis-related encephalopathy, epidemic encephalitis B and other diseases. In addition, this study attempts to explore the possible mechanism of QBD in the prevention and treatment of COVID-19. Through the analysis of the chemical substances, pharmacological action and mechanism of QBD, this paper will provide a reference theoretical basis for the prevention and treatment of COVID-19 by QBD.
Rare musculoskeletal diseases in adults: a research priority setting partnership with the James Lind Alliance
Authors: Mickute Gerda , Staley Kristina , Delaney Heather , Gardiner Oliver , Hunter Amy , Keen Richard , Lockhart Lorraine , Meade Nick , Newman Maria , Ralston Stuart , Rush Elaine , Upadhyaya Sheela , Regan Sandra , Watts Laura , Walsh Jennifer , White Paul , Francis Roger M. , Javaid M. Kassim 
Published: May 2020

Abstract
Background
Osteogenesis imperfecta, fibrous dysplasia/McCune-Albright syndrome and X-linked hypophosphatemia are three rare musculoskeletal diseases characterised by bone deformities, frequent fractures and pain. Little high-quality research exists on appropriate treatment and long-term management of these conditions in adults. This is further worsened by limited research funding in rare diseases and a general mismatch between the existing research priorities and those of the patients. This partnership adopted the James Lind Alliance approach to identify the top 10 research priorities for rare musculoskeletal diseases in adults through joint patient, carer and healthcare professional collaboration.

Results
The initial survey for question collection recruited 198 respondents, submitting a total of 988 questions. 77% of the respondents were patients with a rare musculoskeletal disease. Following out-of-scope question exclusion, repeating query grouping and scientific literature check for answers, 39 questions on treatment and long-term management remained. In the second public survey, 220 respondents, of whom 85% were patients with a rare musculoskeletal disease, their carers, relatives or friends, prioritised these uncertainties, which allowed selection of the top 25. In the last stage, patients, carers and healthcare professionals gathered for a priority setting workshop to reach a consensus on the final top 10 research priorities. These focus on the uncertainties surrounding appropriate treatment and holistic long-term disease management, highlighting several aspects indirect to abnormal bone metabolism, such as extra-skeletal symptoms, psychological care of both patients and their families and disease course through ageing.

Conclusions
This James Lind Alliance priority setting partnership is the first to investigate rare bone diseases. The priorities identified here were developed jointly by patients, carers and healthcare professionals. We encourage researchers, funding bodies and other stakeholders to use these priorities in guiding future research for those affected by rare musculoskeletal disorders.