bluuebunny/crossref_metadata_2025 huggingface dataset:
Venezuelan equine encephalitis virus: the problem is not over for tropical America
Authors: Guzmán-Terán Camilo , Calderón-Rangel Alfonso , Rodriguez-Morales Alfonso , Mattar Salim
Published: May 2020

The equine encephalitis viruses, Venezuelan (VEEV), East (EEEV) and West (WEEV), belong to the genus alphavirus, family Togaviridae and still represent a threat for human and animal public health in the Americas. In both, these infections are characterized by high viremia, rash, fever, encephalitis and death. VEEV encephalitis is similar, clinically, to other arboviral diseases, such as dengue, Zika or chikungunya. Most of the alphaviruses are transmitted between vertebrates and mosquitoes. They are able to replicate in a wide number of hosts, including mammals, birds, reptiles, amphibian and arthropods. The VEEV has enzootic and epizootic transmission cycles. At the enzootic one, enzootic strains (subtype I, serotypes D–F and serotypes II–VI) are continuously circulating between mosquitoes and wild rodents in tropical forests and mangroves of the Americas. The main reseroivrs are wild rodent species of the subfamilySigmodontinae. However, bats can be also accidental reservoirs of VEEV. In this article, we reviewed the main features, epidemiology, clinical aspects and the current perspectives of the VEEV.
Circular RNA circMET drives immunosuppression and anti-PD1 therapy resistance in hepatocellular carcinoma via the miR-30-5p/snail/DPP4 axis
Authors: Huang Xiao-Yong , Zhang Peng-Fei , Wei Chuan-Yuan , Peng Rui , Lu Jia-Cheng , Gao Chao , Cai Jia-Bing , Yang Xuan , Fan Jia , Ke Ai-Wu , Zhou Jian , Shi Guo-Ming
Published: May 2020

Background

Amplification of chromosome 7q21-7q31 is associated with tumor recurrence and multidrug resistance, and several genes in this region are powerful drivers of hepatocellular carcinoma (HCC). We aimed to investigate the key circular RNAs (circRNAs) in this region that regulate the initiation and development of HCC.

Methods

We used qRT-PCR to assess the expression of 43 putative circRNAs in this chromosomal region in human HCC and matched nontumor tissues. In addition, we used cultured HCC cells to modify circRNA expression and assessed the effects in several cell-based assays as well as gene expression analyses via RNA-seq. Modified cells were implanted into immunocompetent mice to assess the effects on tumor development. We performed additional experiments to determine the mechanism of action of these effects.

Results

circMET (hsa_circ_0082002) was overexpressed in HCC tumors, and circMET expression was associated with survival and recurrence in HCC patients. By modifying the expression of circMET in HCC cells in vitro, we found that circMET overexpression promoted HCC development by inducing an epithelial to mesenchymal transition and enhancing the immunosuppressive tumor microenvironment. Mechanistically, circMET induced this microenvironment through the miR-30-5p/Snail/ dipeptidyl peptidase 4(DPP4)/CXCL10 axis. In addition, the combination of the DPP4 inhibitor sitagliptin and anti-PD1 antibody improved antitumor immunity in immunocompetent mice. Clinically, HCC tissues from diabetic patients receiving sitagliptin showed higher CD8+ T cell infiltration than those from HCC patients with diabetes without sitagliptin treatment.

Conclusions

circMET is an onco-circRNA that induces HCC development and immune tolerance via the Snail/DPP4/CXCL10 axis. Furthermore, sitagliptin may enhance the efficacy of anti-PD1 therapy in a subgroup of patients with HCC.
A systematic review and meta-analysis of serum cholesterol and triglyceride levels in patients with Parkinson’s disease
Authors: Fu Xiaoxue , Wang Yu , He Xiaofeng , Li Hongyu , Liu Hong , Zhang Xiangyang
Published: May 2020

Objectives

Numerous studies have reported that lipid metabolic abnormalities may play an important role in the development of Parkinson’s disease (PD), with mixed results. This meta-analysis aims to systematically assess the relationship between serum cholesterol or triglyceride and the PD risk and to further determine the role of dyslipidemia in potential predictive value.

Methods

This research systematically consulted and screened observational studies to evaluate the association of serum lipids with the risk of PD as of April 01, 2020 based on the inclusion and exclusion criteria. Two researchers screened and extracted the data independently. Then this article summarized the characteristics of all clinical studies and collected the corresponding data to perform pooled and sensitivity analyses. The meta-analysis was performed by using the RevMan 5.3 software after data extraction, quality assessment and analysis of publication bias.

Results

Twenty-one related studies (13 case-control and 8 cohort studies) were selected with a total of 980,180 subjects, including 11,188 PD patients. Meta-analysis showed that higher levels of serum triglyceride (S-TG) [standard mean different (SMD) = − 0.26 (95% confidence interval (CI): − 0.39 to − 0.13, p<0.00001), relative risk (RR) = 0.67 (95% CI: 0.60 to 0.75, p<0.00001)] could be considered as protective factors for the pathogenesis of PD. However, there was no significant association between serum high density lipoprotein cholesterol (S-HDL) and the risk of PD. Meanwhile, serum low density lipoprotein cholesterol (S-LDL) [SMD = -0.26 (95% CI: − 0.43 to − 0.07, p = 0.006), RR = 0.76 (95% CI: 0.59 to 0.97, p = 0.03)] and serum total cholesterol (S-TC) levels [SMD = -0.21 (95% CI: − 0.33 to − 0.10, p = 0.0002), RR = 0.86 (95% CI: 0.77 to 0.97, p = 0.01)] were negatively associated with PD risk.

Conclusions

This systematic review suggests that elevated serum levels of TG, LDL and TC may be protective factors for the pathogenesis of PD. Further longitudinal and well-designed prospective studies with a large sample size are needed to confirm the findings in this meta-analysis.
Correction to: Astaxanthin-loaded polymer-lipid hybrid nanoparticles (ATX-LPN): assessment of potential otoprotective effects
Authors: Gu Jiayi , Chen Yuming , Tong Ling , Wang Xueling , Yu Dehong , Wu Hao
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Correction to: Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action
Authors: Marycz K. , Sobierajska P. , Roecken M. , Kornicka-Garbowska K. , Kępska M. , Idczak R. , Nedelec J.-M. , Wiglusz R. J.
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Proteome-wide identification of arginine methylation in colorectal cancer tissues from patients
Authors: Lim Yongchul , Lee Ju Yeon , Ha Su Jin , Yu Suyeun , Shin Jung Kyong , Kim Hee Cheol
Published: May 2020

Background

Protein arginine methylation reaction is catalyzed by protein arginine methyltransferase (PRMT) and the modification is implicated in various diseases including cancer. Currently, thousands of arginine methylation sites have been identified using high-resolution mass spectrometry-based proteomics technology. However, identification of arginine methylation using clinical samples at proteome level has not been reported yet. The objective of the present study was to identify, monomethyl-arginine (MMA) and asymmetric dimethyl-arginine (ADMA) sites in colorectal cancer (CRC) tissues at proteome level.

Methods

Pooled CRC tissue samples from 10 patients with stage II and III were digested by trypsin and these digests were further processed and lyophilized. Using monomethyl- or asymmetric dimethyl arginine (MMA or ADMA, respectively) motif kits, methylarginine-containing peptides were enriched and subsequently analyzed by high-resolution LC-MS/MS. DLD1 and HCT116 colon cancer cells were treated with type I PRMTs inhibitor (MS023) alone or combined with SN-38, and the effect of the drugs on CRC cell proliferation and apoptosis was measured by water-soluble tetrazolium salt (WST-1) assay and FACS analysis, respectively.

Results

In the present study, 455 MMA sites of 272 proteins and 314 ADMA sites of 155 proteins were identified from CRC tissues acquired from patients. In addition, 216 methylation sites and 75 substrates for PRMTs were newly identified. These results reveal the significant presence of MMA and ADMA sites on nucleic acid binding proteins and protein complexes involved in transcription. To investigate the effect of protein arginine methylation in CRC proliferation and apoptosis, MS023 was treated to two CRC cell lines. After 48 h treatment with various concentrations of MS023, CRC cell proliferation was significantly suppressed, with concomitant apoptosis induction. Furthermore, MS023 treatment significantly enhanced the inhibitory effect of SN-38 on CRC cell proliferation.

Conclusion

This work reports the first comprehensive analysis of arginine methylation with clinical sample and suggests that type I PRMTs are potential therapeutic targets for drug discovery in CRC.
Cost-utility analysis in chronic kidney disease patients undergoing kidney transplant; what pays? A systematic review
Authors: Senanayake Sameera , Graves Nicholas , Healy Helen , Baboolal Keshwar , Kularatna Sanjeewa
Published: May 2020

Background

Health systems are under pressure to deliver more effective care without expansion of resources. This is particularly pertinent to diseases like chronic kidney disease (CKD) that are exacting substantial financial burden to many health systems. The aim of this study is to systematically review the Cost Utility Analysis (CUA) evidence generated across interventions for CKD patients undergoing kidney transplant (KT).

Methods

A systemic review of CUA on the interventions for CKD patients undergoing KT was carried out using a search of the MEDLINE, CINAHL, EMBASE, PsycINFO and NHS-EED. The CHEERS checklist was used as a set of good practice criteria in determining the reporting quality of the economic evaluation. Quality of the data used to inform model parameters was determined using the modified hierarchies of data sources.

Results

A total of 330 articles identified, 16 met the inclusion criteria. Almost all (n = 15) the studies were from high income countries. Out of the 24 characteristics assessed in the CHEERS checklist, more than 80% of the selected studies reported 14 of the characteristics. Reporting of the CUA were characterized by lack of transparency of model assumptions, narrow economic perspective and incomplete assessment of the effect of uncertainty in the model parameters on the results. The data used for the economic model were satisfactory quality. The authors of 13 studies reported the intervention as cost saving and improving quality of life, whereas three studies were cost increasing and improving quality of life. In addition to the baseline analysis, sensitivity analysis was performed in all the evaluations except one. Transplanting certain high-risk donor kidneys (high risk of HIV and Hepatitis-C infected kidneys, HLA mismatched kidneys, high Kidney Donor Profile Index) and a payment to living donors, were found to be cost-effective.

Conclusions

The quality of economic evaluations reviewed in this paper were assessed to be satisfactory. Implementation of these strategies will significantly impact current systems of KT and require a systematic implementation plan and coordinated efforts from relevant stakeholders.
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

Background

The 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.

Methods

Biochemical 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.

Results

Our 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.

Conclusions

Overall, 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
Correction to: PTH Derivative promotes wound healing via synergistic multicellular stimulating and exosomal activities
Authors: Shen Yi-Fan , Huang Jing-Huan , Wang Kai-Yang , Zheng Jin , Cai Lin , Gao Hong , Li Xiao-Lin , Li Jing-Feng
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
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

The 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

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

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

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

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

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

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

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

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

The 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

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.
RETRACTED ARTICLE: The circular RNA 001971/miR-29c-3p axis modulates colorectal cancer growth, metastasis, and angiogenesis through VEGFA
Authors: Chen Chen , Huang Zhiguo , Mo Xiaoye , Song Yanmin , Li Xiangmin , Li Xiaogang , Zhang Mu
Published: May 2020

Background

Colorectal cancer (CRC) is one of the most common malignant tumors globally. Angiogenesis is a key event maintaining tumor cell survival and aggressiveness. The expression of vascular endothelial growth factor A (VEGFA), one of the most significant tumor cell-secreted proangiogenic factors, is frequently upregulated in CRC.

Methods

The MTT assay was used to detect the viability of CRC cells. Transwell assays were performed to detect the invasion capacity of target cells. Relative protein levels were determined by immunoblotting. Pathological characteristics of tissues were detected by H&E staining and immunohistochemical (IHC) staining. A RIP assay was conducted to validate the predicted binding between genes.

Results

We observed that circ-001971 expression was dramatically increased in CRC tissue samples and cells. Circ-001971 knockdown suppressed the capacity of CRC cells to proliferate and invade and HUVEC tube formation in vitro, as well as tumor growth in mice bearing SW620 cell-derived tumors in vivo. The expression of circ-001971 and VEGFA was dramatically increased whereas the expression of miR-29c-3p was reduced in tumor tissue samples. Circ-001971 relieved miR-29c-3p-induced inhibition of VEGFA by acting as a ceRNA, thereby aggravating the proliferation, invasion and angiogenesis of CRC. Consistent with the above findings, the expression of VEGFA was increased, whereas the expression of miR-29c-3p was decreased in tumor tissue samples. miR-29c-3p had a negative correlation with both circ-001971 and VEGFA, while circ-001971 was positively correlated with VEGFA.

Conclusions

In conclusion, the circ-001971/miR-29c-3p axis modulated CRC cell proliferation, invasion, and angiogenesis by targeting VEGFA.
Organizational changes in diabetic foot care practices for patients at low and moderate risk after implementing a comprehensive foot care program in Alberta, Canada
Authors: Chan Catherine B. , Dmytruk Kathy , Labbie Michele , O'Connell Petra
Published: May 2020

Background

Neuropathy and vasculopathy can lead to costly and debilitating complications in people with diabetes. The purpose of this study was to evaluate, at an organizational level, uptake of practices included in a diabetic foot care clinical pathway and associated resources. This research focused on patients at low and moderate risk in Alberta, Canada between 2014 to 2019.

Methods

Serial surveys (2014, 2019) of practices related to screening and care of the feet of people with diabetes. Surveys were administered using a combination of targeted and snowball sampling in order to assess the impact of the clinical pathway first implemented in 2015. The pathway focused on screening, assessment and referral of patients from primary care. High‐risk foot teams (HRFT) were established at six sites to provide increased access to specialty care. Comparative statistics were performed to assess differences in footcare practices between 2014 and 2019 using two‐tailed Fisher's exact test or Chi‐square test.

Results

Respondents (n = 104, 2014 and n = 75, 2019) included personnel from primary health care, home care and long‐term care, acute and emergency care, specialty clinics, diabetes‐specific programs and private contractors. The proportion of primary care and home care/long‐term care (HC/LTC) sites providing screening increased significantly (p < 0.05). A significant increase in the proportion of sites providing assessment for patients designated as moderate risk also increased from 35% (34 out of 96 sites) to 55% (36 out of 65 sites) (p < 0.05), particularly with respect to vascular assessment, and the proportion of sites reporting appropriate follow‐up intervals according to the pathway recommendation was also improved.

Conclusion

Provision of a clinical pathway for diabetic foot care along with education and resources led to increased screening in primary care and HC/LTC settings in Alberta, Canada. HRFT provided primary healthcare providers with an important option for referral and also provided increased expertise for procedures such as vascular assessment for patients with moderate risk of ulceration. This comprehensive model has the potential to reduce progression of foot problems and overall health services utilization. Further analyses of outcomes such as incident lower limb amputation and long‐term cost‐effectiveness of pathway implementation are underway.
Proteomics analysis of plasma protein changes in patent ductus arteriosus patients
Authors: Xu Cheng , Su Xiaoqi , Chen Yong , Xu Yang , Wang Zhiqi , Mo Xuming
Published: May 2020

Objective

Patent ductus arteriosus (PDA) is a congenital heart defect with an unclear etiology that occurs commonly among newborns. Adequately understanding the molecular pathogenesis of PDA can contribute to improved treatment and prevention. Plasma proteins may provide evidence to explore the molecular mechanisms of abnormal cardiac development.

Methods

Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics technology was used to measure different plasma proteins in PDA patients (n = 4) and controls (n = 4). The candidate protein was validated by ELISA and Western blot (WB) assays in a larger sample. Validation of the location and expression of this protein was performed in mouse heart sections.

Results

There were three downregulated proteins and eight upregulated proteins identified in the iTRAQ proteomics data. Among these, protein disulfide-isomerase A6 (PDIA6) was further analyzed for validation. The plasma PDIA6 concentrations (3.2 ± 0.7 ng/ml) in PDA patients were significantly lower than those in normal controls (5.8 ± 1.2 ng/ml). In addition, a WB assay also supported these results. PDIA6 was widely expressed in mouse heart outflow tract on embryonic day 14.5.

Conclusion

Plasma proteomics profiles suggested novel candidate molecular markers for PDA. The findings may allow development of a new strategy to investigate the mechanism and etiology of PDA.
Mortality in sepsis and septic shock in Europe, North America and Australia between 2009 and 2019— results from a systematic review and meta-analysis
Authors: Bauer Michael , Gerlach Herwig , Vogelmann Tobias , Preissing Franziska , Stiefel Julia , Adam Daniel
Published: May 2020

Background

Sepsis and septic shock remain drivers for mortality in critically ill patients. The heterogeneity of the syndrome hinders the generation of reproducible numbers on mortality risks. Consequently, mortality rates range from 15 to 56%. We aimed to update and extend the existing knowledge from meta-analyses and estimate 30- and 90-day mortality rates for sepsis and septic shock separately, stratify rates by region and study type and assess mortality rates across different sequential organ failure assessment (SOFA) scores.

Methods

We performed a systematic review of articles published in PubMed or in the Cochrane Database, between 2009 and 2019 in English language including interventional and observational studies. A meta-analysis of pooled 28/30- and 90-day mortality rated separately for sepsis and septic shock was done using a random-effects model. Time trends were assessed via Joinpoint methodology and for the assessment of mortality rate over different SOFA scores, and linear regression was applied.

Results

Four thousand five hundred records were identified. After title/abstract screening, 783 articles were assessed in full text for eligibility. Of those, 170 studies were included. Average 30-day septic shock mortality was 34.7% (95% CI 32.6–36.9%), and 90-day septic shock mortality was 38.5% (95% CI 35.4–41.5%). Average 30-day sepsis mortality was 24.4% (95% CI 21.5–27.2%), and 90-day sepsis mortality was 32.2% (95% CI 27.0–37.5%). Estimated mortality rates from RCTs were below prospective and retrospective cohort studies. Rates varied between regions, with 30-day septic shock mortality being 33.7% (95% CI 31.5–35.9) in North America, 32.5% (95% CI 31.7–33.3) in Europe and 26.4% (95% CI 18.1–34.6) in Australia. A statistically significant decrease of 30-day septic shock mortality rate was found between 2009 and 2011, but not after 2011. Per 1-point increase of the average SOFA score, average mortality increased by 1.8–3.3%.

Conclusion

Trends of lower sepsis and continuous septic shock mortality rates over time and regional disparities indicate a remaining unmet need for improving sepsis management. Further research is needed to investigate how trends in the burden of disease influence mortality rates in sepsis and septic shock at 30- and 90-day mortality over time.
Toxoplasma gondii in the Eurasian kestrel (Falco tinnunculus) in northern Italy
Authors: Iemmi Tiziano , Vismarra Alice , Mangia Carlo , Zanin Rolando , Genchi Marco , Lanfranchi Paolo , Kramer Laura Helen , Formenti Nicoletta , Ferrari Nicola
Published: May 2020

Background

Identifying factors that sustain parasite transmission is important for understanding their spread and emergence, including how changes in biodiversity may affect parasite prevalence and spread.Toxoplasma gondiiis a protozoan parasite infecting humans and animals. Birds can acquireT. gondiiinfection through ingestion either of oocysts from the ground or of tissue cysts present in infected prey and are therefore suitable indicators of the presence ofT. gondiiin the natural environment.

Methods

The aim of the study included the evaluation ofT. gondiiseroprevalence in clinically healthy Eurasian kestrels (Falco tinnunculus) using a modified agglutination test. Birds were captured in a small area of Parma (northern Italy) for two consecutive years (2016–2017), sex and age determined and serological study carried out. Food sources for the birds were also evaluated, in particular rodent and grasshopper population estimates in the study area. The biomass of rodents and grasshoppers per hectare was estimated in order to directly compare food availability. Statistical analyses were performed in order to evaluate factors influencing the probability of kestrels beingT. gondii-seropositive using R 3.4.4 fitting linear mixed-effect models with the ‘glmer’ function of the packagelme4, ‘lsmean’ in packagelsmeanfor pair-wise post-hoc comparisons using differences of least square means (DLSM) and the ‘betareg’ function of the packagebetaregfor beta regression.

Results

Seroprevalence forT. gondiiwas 33.3% (49/147) in 2016, while in 2017 seroprevalence decreased to 14.3% (13/91). An increase in the probability of kestrels beingT. gondii-seropositive was associated with a higher rodent biomass in the environment, suggesting a positive feedback of the biotic factors driving infection risk.

Conclusions

These results underline the need for multidisciplinary studies aimed at better understanding pathogen-host relationships and for predictions in disease ecology.
Overexpression of MIG-6 in the cartilage induces an osteoarthritis-like phenotype in mice
Authors: Bellini Melina , Pest Michael A. , Miranda-Rodrigues Manuela , Qin Ling , Jeong Jae-Wook , Beier Frank
Published: May 2020

Background

Osteoarthritis (OA) is the most common form of arthritis and characterized by degeneration of the articular cartilage. Mitogen-inducible gene 6 (Mig-6) has been identified as a negative regulator of the epidermal growth factor receptor (EGFR). Cartilage-specific Mig-6 knockout (KO) mice display increased EGFR signaling, an anabolic buildup of the articular cartilage, and formation of chondro-osseous nodules. Since our understanding of the EGFR/Mig-6 network in the cartilage remains incomplete, we characterized mice with cartilage-specific overexpression of Mig-6 in this study.

Methods

Utilizing knee joints from cartilage-specific Mig-6-overexpressing (Mig-6over/over) mice (at multiple time points), we evaluated the articular cartilage using histology, immunohistochemical staining, and semi-quantitative histopathological scoring (OARSI) at multiple ages. MicroCT analysis was employed to examine skeletal morphometry, body composition, and bone mineral density.

Results

Our data show that cartilage-specific Mig-6 overexpression did not cause any major developmental abnormalities in the articular cartilage, although Mig-6over/over mice have slightly shorter long bones compared to the control group. Moreover, there was no significant difference in bone mineral density and body composition in any of the groups. However, our results indicate that Mig-6over/over male mice show accelerated cartilage degeneration at 12 and 18 months of age. Immunohistochemistry for SOX9 demonstrated that the number of positively stained cells in Mig-6over/over mice was decreased relative to controls. Immunostaining for MMP13 appeared increased in areas of cartilage degeneration in Mig-6over/over mice. Moreover, staining for phospho-EGFR (Tyr-1173) and lubricin (PRG4) was decreased in the articular cartilage of Mig-6over/over mice.

Conclusion

Overexpression of Mig-6 in the articular cartilage causes no major developmental phenotype; however, these mice develop earlier OA during aging. These data demonstrate that Mig-6/EGFR pathways are critical for joint homeostasis and might present a promising therapeutic target for OA.