bluuebunny/crossref_metadata_2025_split huggingface dataset:
The histone demethylase JMJD2A promotes glioma cell growth via targeting Akt-mTOR signaling
Authors: Li Min , Cheng Jingmin , Ma Yuan , Guo Heng , Shu Haifeng , Huang Haidong , Kuang Yongqin , Yang Tao 
Published: March 2020

Abstract
Background
A number of JmjC domain-containing histone demethylases have been identified and biochemically characterized in mammalian models and humans. JMJD2A is a transcriptional co-factor and enzyme that catalyzes the demethylation of histone H3 lysine 9 and 36 (H3K9 and H3K36). Here in this study, we reported the role of JMJD2A in human glioma.

Methods
Quantitative real-time PCR and western blot were performed to analyzed JMJD2A expression in glioma. Log-rank was performed to plot the survival curve. JMJD2A was knocked or overexpressed with lentivirus. Cell proliferation and colony formation were performed to assess the effects of JMJD2A on glioma cell growth. Xenograft experiment was performed the evaluate the growth rate of glioma cells in vivo. The signaling pathway was analyzed with western blot and mTOR was inhibited with rapamycin.

Results
Quantitative real-time PCR and western blot experiments revealed higher expression of JMJD2A and lower levels of H3K9me3/H3K36me3 in glioma tissues than that in normal brain tissues. We showed that knockdown of JMJD2A expression attenuated the growth and colony formation in three lines of glioma cells (U251, T98G, and U87MG), whereas JMJD2A overexpression resulted in opposing effects. Furthermore, we performed in vivo xenograft experiments and our data demonstrated that JMJD2A knockdown reduced the growth of glioma T98G cells in vivo. Further mechanism study implicated that JMJD2A activated the Akt-mTOR pathway and promoted protein synthesis in glioma cells via promoting phosphoinositide-dependent kinase-1 (PDK1) expression. The activation of the Akt-mTOR pathway was also validated in human glioma tissues. Finally, we showed that inhibition of mTOR with rapamycin blocked the effects of JMJD2A on protein synthesis, cell proliferation and colony formation of glioma cells.

Conclusions
These findings demonstrated that JMJD2A regulated glioma growth and implicated that JMJD2A might be a promising target for intervention.
Overexpression of FES might inhibit cell proliferation, migration, and invasion of osteosarcoma cells
Authors: Zhao Yang , Wang Zhimeng , Wang Qian , Sun Liang , Li Ming , Ren Cheng , Xue Hanzhong , Li Zhong , Zhang Kun , Hao Dingjun , Yang Na , Song Zhe , Ma Teng , Lu Yao 
Published: March 2020

AbstractBackgroundThis study aimed to screen osteosarcoma (OS) prognosis relevant genes for methylation dysregulation, and the functional mechanisms of FES overexpression in OS cells were investigated.MethodsThe OS prognosis relevant genes with differentially methylated positions (DMPs) identified from the GSE36001 and GSE36002 datasets, and the UCSC database, were used as a training set to construct a risk model, while the GSE21257 dataset was used as validation set. The expression levels of several key genes in OS cells after 5-Aza-2′-deoxycytidine treatment were detected by qPCR. The effects of FES overexpression on cell proliferation, cell cycle, migration, and invasion of MNNG/HOS were analyzed by CCK8, flow cytometry, and Transwell assays.ResultsA total of 31 candidate genes, corresponding to 36 DMPs, were identified as OS prognosis relevant genes; from these, the top 10 genes were used to construct a risk model. Following validation of the risk model, FES, LYL1, MAP4K1, RIPK3, SLC15A3, and STAT3 showed expression changes between the OS and control samples. qPCR results showed that the expression of FES was significantly downregulated in three OS cell lines and increased after 5-Aza-DC treatment. The proliferation, cell cycle progression, migration, and invasion of MNNG/HOS cells were significantly inhibited after transfection with FES overexpression plasmid, and the protein expression of FYN and β catenin were decreased in MNNG/HOS cells by FES overexpression.ConclusionsThe decrease in FES by hypermethylation was associated with OS prognosis, and might contribute to the proliferation, migration, and invasion of OS cells. FES, and its upstream FYN and β catenin, might coordinately exert a tumor suppressor effect in OS cells.
MicroRNA-122-5p inhibits cell proliferation, migration and invasion by targeting CCNG1 in pancreatic ductal adenocarcinoma
Authors: Dai Chen , Zhang Yan , Xu Zhihua , Jin Mengxian 
Published: March 2020

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a lethal human malignancy, and previous researches support the contribution of microRNA (miRNA) to cancer progression. MiR-122-5p is reported to participate in the regulation of various cancers, while the function of miR-122-5p in PDAC remains unclear. In this study, we investigated the precise mechanism of miR-122-5p involved in PDAC pathogenesis.

Methods
The expression levels of miR-122-5p were detected in human PDAC tissues and cell lines by miRNA RT-PCR. The effects of miR-122-5p on cell proliferation were explored by MTT assays, colony formation assays and flow cytometry assays. The ability of migration and invasion was determined by transwell assays. Dual Luciferase reporter assay was performed to validate the direct interaction between miR-122-5p and its target gene. The related molecules of cell cycle, apoptosis and epithelial–mesenchymal transition (EMT) were examined with qRT-PCR and western blot. In addition, xenograft mouse models were applied to explore the effects of miR-122-5p in vivo.

Results
MiR-122-5p was underexpressed, while CCNG1 was highly expressed in PDAC tissues and cells. MiR-122-5p was negatively correlated with TNM stage, tumor size and lymph node metastasis in PDAC patients. Overexpression of miR-122-5p suppressed the proliferation, migration and invasion in vitro and inhibited tumorigenesis in vivo. Furthermore, CCNG1 was a direct target of miR-122-5p. Upregulated CCNG1 could partially reverse the effects caused by miR-122-5p. Moreover, miR-122-5p inhibited EMT through downregulation of CCNG1.

Conclusion
Overexpression of miR-122-5p could inhibit cell proliferation, migration, invasion, and EMT by downregulating CCNG1 in PDAC, suggesting a potential therapeutic target for PDAC.
Comparison of fungal and bacterial keratitis between tropical and subtropical Taiwan: a prospective cohort study
Authors: Chen Chih-An , Hsu Shiuh-Liang , Hsiao Ching-Hsi , Ma David Hui-Kang , Sun Chi-Chin , Yu Hun-Ju , Fang Po-Chiung , Kuo Ming-Tse 
Published: March 2020

Abstract
Background
Fungal keratitis (FK) has been shown to be a climate-sensitive disease. The differentiation between FK from bacterial keratitis (BK) was difficult. The purpose of this study was to compare the bacteriology and mycology between tropical and subtropical Taiwan and to investigate the independent risk factors for identification of fungi from bacteria.

Methods
Two hundred ninety-seven patients with clinical suspected microbial keratitis were prospectively enrolled. A fungal to bacteria rate (FBR), the number of fungi divided by bacteria identified, was determined to estimate the prevalence of fungi and bacteria. Clinical presentation, profiles of microorganisms, and predisposing risk factors were determined. Univariate and multivariate logistic regression analysis were used to investigate the independent risk factors.

Results
A total of 82 fungi and 143 bacteria were laboratory confirmed. The identification rate of fungus was higher in tropical Taiwan (p = 0.010). Among the fungi and bacteria confirmed, the FBR was 0.29 (22.4% vs. 77.6%) in subtropical Taiwan, and 0.70 (41.3% vs. 58.7%) in tropical Taiwan. Samples obtained in tropical area (p = 0.019), ocular trauma (p = 0.019), and plant exposure (p = 0.003) were independent risk factors for identification of fungus from bacteria. The predominant fungus isolated from corneal scraping were Fusarium solani (25%) and Trichosporon faecale (25%) in subtropical Taiwan; in tropical Taiwan was Fusarium spp. (50%).

Conclusions
The identification rate of fungus was higher in tropical Taiwan than subtropical Taiwan. Awareness of the local epidemiology is crucial for early diagnosis of fungal keratitis in tropical area.
Linear and circular PVT1 in hematological malignancies and immune response: two faces of the same coin
Authors: Ghetti Martina , Vannini Ivan , Storlazzi Clelia Tiziana , Martinelli Giovanni , Simonetti Giorgia 
Published: March 2020

AbstractNon coding RNAs (ncRNAs) have emerged as regulators of human carcinogenesis by affecting the expression of key tumor suppressor genes and oncogenes. They are divided into short and long ncRNAs, according to their length. Circular RNAs (circRNAs) are included in the second group and were recently discovered as being originated by back-splicing, joining either single or multiple exons, or exons with retained introns. The human Plasmacytoma Variant Translocation 1 (PVT1) gene maps on the long arm of chromosome 8 (8q24) and encodes for 52 ncRNAs variants, including 26 linear and 26 circular isoforms, and 6 microRNAs. PVT1 genomic locus is 54 Kb downstream to MYC and several interactions have been described among these two genes, including a feedback regulatory mechanism. MYC-independent functions of PVT1/circPVT1 have been also reported, especially in the regulation of immune responses. We here review and discuss the role of both PVT1 and circPVT1 in the hematopoietic system. No information is currently available concerning their transforming ability in hematopoietic cells. However, present literature supports their cooperation with a more aggressive and/or undifferentiated cell phenotype, thus contributing to cancer progression. PVT1/circPVT1 upregulation through genomic amplification or rearrangements and/or increased transcription, provides a proliferative advantage to malignant cells in acute myeloid leukemia, acute promyelocytic leukemia, Burkitt lymphoma, multiple myeloma (linear PVT1) and acute lymphoblastic leukemia (circPVT1). In addition, PVT1 and circPVT1 regulate immune responses: the overexpression of the linear form in myeloid derived suppressor cells induced immune tolerance in preclinical tumor models and circPVT1 showed immunosuppressive properties in myeloid and lymphoid cell subsets. Overall, these recent data on PVT1 and circPVT1 functions in hematological malignancies and immune responses reflect two faces of the same coin: involvement in cancer progression by promoting a more aggressive phenotype of malignant cells and negative regulation of the immune system as a novel potential therapy-resistance mechanism.
Elevated soluble TNFα levels and upregulated TNFα mRNA expression in purified peripheral blood monocyte subsets associated with high-grade hepatocellular carcinoma
Authors: Martín-Sierra C. , Martins R. , Coucelo M. , Abrantes A. M. , Oliveira R. C. , Tralhão J. G. , Botelho M. F. , Furtado E. , Domingues M. R. , Paiva A. , Laranjeira P. 
Published: March 2020

Abstract
Background
Chronic inflammation is involved in the initiation and progression of various cancers, including liver cancer. The current study focuses on the characterization of the peripheral immune response in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patients, before and after surgical procedure, in order to assess the effect of tumor resection in the immune system homeostasis and to determine possible prognostic factors associated with high-grade tumors. We developed a whole-blood assay to monitor immune alterations and functional competence of peripheral monocytes in a group of 10 healthy individuals (HG), in 20 HCC patients and 8 CCA patients, by multi-color flow cytometry, qRT-PCR, and ELISA techniques.

Results
The qRT-PCR analysis showed an upregulation of TNFα expression by classical and intermediate monocytes purified from HCC patients presenting tumors in grade G3-G4 as compared to G1-G2 HCC patients. Moreover, ELISA assay confirmed elevated serum levels of TNFα in G3-G4 compared to G1-G2 HCC patients. A significant decrease of circulating non-classical monocytes was detected in both CCA and HCC patients before and after surgical procedure. In addition, a functional defect in circulating classical and intermediate monocytes was observed in both groups of cancer patients when compared to the HG, with partial recovery after the surgical intervention.

Conclusions
This integrated analysis permitted the identification of altered functional competence of monocyte subsets in CCA and HCC patients. In addition, our results point to a potential role of TNFα as a prognostic peripheral biomarker in HCC patients, indicating the presence of high-grade tumors that should be further validated.
Health-related quality of life in porphyria cutanea tarda: a cross-sectional registry based study
Authors: Andersen Janice , Thomsen Janne , Enes Åshild Rostad , Sandberg Sverre , Aarsand Aasne K. 
Published: March 2020

Abstract
Background
Porphyria cutanea tarda (PCT) is a rare, photosensitive disease characterized by skin fragility and blistering on sun-exposed areas. There is little previous research on how this condition affects health-related quality of life (HRQoL) and to the best of our knowledge this is the largest sample of PCT patients surveyed about their HRQoL. The aims of this study were to describe HRQoL, symptoms, susceptibility factors, disease activity and treatment in patients with PCT, and investigate the associations between these factors.

Methods
This is a cross-sectional, retrospective study based on patient-reported outcome and laboratory data. The Norwegian Porphyria Centre diagnoses all patients with PCT in Norway, all of whom are invited to participate in the Norwegian Porphyria Registry. Between December 2013–2015, 111 patients received a postal questionnaire and invitation to participate.

Results
Sixty-eight persons responded, with seven being excluded due to prolonged response time or missing information, resulting in 61 participants in the final analyses (55%). Median age was 60 years and 33 were female. We found a moderate negative relationship between the type and localisation of PCT symptoms and both mental (r = −.354 p < 0.01) and physical (r = −.441, p < 0.01) aspects of HRQoL. Participants who had started treatment when answering the questionnaire reported significantly better physical functioning and less bodily pain than those who had not started treatment. We did not observe an association between biochemical markers of disease activity and symptoms or HRQoL. Itching, a symptom that has received little attention in PCT was reported by 59% of the participants.

Conclusions
Our results show that reduced HRQoL is associated with more symptoms and not having started treatment. PCT is a rare disease, and there is a need for the development of best-practice guidelines to facilitate good patient care.
Risk factors for limited improvement after total trapeziometacarpal joint arthroplasty
Authors: Mosegaard Sebastian Breddam , Stilling Maiken , Hansen Torben Bæk 
Published: March 2020

Abstract
Background
Trapeziometacarpal (TMC) osteoarthritis can be painful and cause disability for patients. Total joint replacement of the TMC joint provides a pseudo arthrosis with good restoration of the thumb motion and pain relief in most patients. But there is also a risk of no improvement following the operation. The purpose of this study was to identify patients at risk of no clinically important improvement following operative treatment of osteoarthritis of the TMC joint.

Methods
We included 287 consecutive patients (225 women, 62 men) treated with total joint replacement of the TMC joint due to osteoarthritis with a mean age of 58.9 years (range 41–80) in a prospective cohort study. We collected information preoperatively and 12 months postoperatively on disabilities of the arm, shoulder and hand score (DASH), grip strength and pain at rest and activity on a visual analogue scale (VAS).Results: We found a statistically significant improvement in DASH from 42.0 to 15.9 (p < 0.001), VAS at rest from 3.5 to 0.6 (p < 0.001), VAS at activity from 7.9 to 2.5 (p < 0.001) and grip strength from 21.6 kg to 27.6 kg (p < 0.001) 12 months after the operation, when analysed as a group. There was an increased risk of no clinically important improvement in hand function for patients with preoperative high preoperative grip strength. Also, we found an increased risk of no clinically important improvement in female patients when using VAS as outcome.

Conclusion
However, we were unable to detect one isolated preoperative predictor as indicator of successful result after operative treatment of TMC osteoarthritis, and as so it was not possible to establish a clinical valid tool for patient selection before surgery.
Informed consent was obtained from all patients for being included in the study. The study needed no approval from The Regional Committee of Biomedical Research Ethics as the data was collected, as part of our normal pre- and postoperative clinical pathway, but the study is part of an outcome study of the results after total joint arthroplasty (TJA) of the TMC joint registered in Clinicaltrials.gov (NCT01554748).

Trial registration
Clinicaltrials.gov (NCT01554748). Registered 15 March 2012.
Heath related quality of life and associated factors among adults with and without diabetes in Adama city East Shewa, Ethiopia 2019; using generalized structural equation modeling
Authors: Tusa Biruk Shalmeno , Geremew Bisrat Misganaw , Tefera Mekuriaw Alemayehu 
Published: March 2020

Abstract
Background
Diabetes mellitus (DM) is a chronic disease, leading to many complications and substantial decrease in patients’ Health Related Quality of Life (HRQoL). HRQoL among diabetic patients could affect by concurrent various factors. Therefore, analysis of these concomitant factors using generalized structural equation model (GSEM) that takes account the complex network of relationship could be a more utilitarian approach to better understand factor affecting HRQoL. The present study aimed to assesses the level of HRQoL and its associated factors among adults with and without diabetes.

Methods
A comparative cross-sectional study was conducted from March 13 to April 4, 2019 in Adama Hospital and Medical College and Adama city Kebele 2, 4 and 5, East Shewa Ethiopia. Data related to socio-demographics, behavioral, clinical factors and HRQoL were collected from 359 adults with diabetes & 415 adults without diabetes through face to face interviews. Data was entered to Epi-data 3.1 then it was exported to STATA 14 for further analysis. GSEM was employed to verify relationships and association among exogenous, mediating and endogenous variable concurrently.

Results
Diabetic groups had a significant lower mean score in all domains of HRQoL than non- diabetic group (p-value< 0.0001). Depression had a direct negative effect on all domains of HRQoL in both groups. Fasting blood sugar also had a direct negative effect on all domains of HRQoL except social relation. Diabetes mellitus complication had a direct negative effect on both physical and psychological health. Low Medication adherence and poor diabetic self-care activity had a negative direct, indirect and total effect on physical and environmental health through fasting blood sugar.

Conclusion
Diabetic patients had lower HRQoL in all the domains of quality of life. Socio-demographic factor (Age, residence and marital status), clinical factor (Depression & Diabetes mellitus complication) and behavioral factor (diabetic self-care activity and medication adherence) mediated by fasting blood sugar were factor associated HRQoL among the diabetic group. Thus, we recommend that integration of screening for depression and give counseling on medication adherences and diabetic self-care activity along with the already existing DM treatment.
Interpretation and content validity of the items of the numeric rating version short-WORC to evaluate outcomes in management of rotator cuff pathology: a cognitive interview approach
Authors: Furtado Rochelle , MacDermid Joy C. , Bryant Dianne M. , Faber Kenneth J. , Athwal George S. 
Published: March 2020

Abstract
Background
The shortened version of the Western Ontario Rotator Cuff Index (Short-WORC) is a patient reported outcome measure that evaluates quality of life (QoL) of patients with rotator cuff pathology. However, formal content validation of the full or Short-WORC has not been reported. This study aims to understand how 1) people interpret and calibrate responses to items on the Short-WORC and 2) compensatory strategies that might enhance function and thereby affect responses.

Methods
This study uses cognitive interviewing, a qualitative methodology that focuses on the interpretation of questionnaire items. Patients with rotator cuff disorders (n = 10), clinicians (n = 6) and measurement researchers (n = 10) were interviewed using a talk aloud structured interview that evaluated each of the 7 items of the Short-WORC. All interviews were recorded and transcribed verbatim by one researcher (R.F). Analysis was done through an open coding scheme using a previously established framework.

Results
Overall, the items on the Short-WORC were well received by participants. Through the interviews, the 6 themes of: Comprehension, Inadequate response definition, Reference Point, Relevance, Perspective Modifiers and Calibration Across Items emerged. The items of working above the shoulder (90%), compensating with the unaffected arm (88%) and lifting heavy objects (92%) were the most relevant to participants. Participants calibrated their scores on the items of sleeping and styling (19%) the most. Perspective modifiers of gender, influenced the calibrations of items of styling your hair (30%) and dressing or undressing (19%). Compensatory strategies of task-re allocation and using assistive devices/resources were frequently mentioned by participants. Overall, participants had minor comprehension issues, but found the 7- items of the Short-WORC to be relevant to QoL.

Conclusions
Therefore, the findings demonstrate that the Short-WORC is not cognitively complex, but varies with patient perspectives. Overall, the Short-WORC provides evidence of demonstrating strong content validity when used for rotator cuff disorder patients.