bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analyses of competing endogenous RNA networks reveal potential biomarkers for predicting hepatocellular carcinoma recurrence
Authors: Yan Ping , Huang Zuotian , Mou Tong , Luo Yunhai , Liu Yanyao , Zhou Baoyong , Cao Zhenrui , Wu Zhongjun 
Published: April 2021

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors, with a high rate of recurrence worldwide. This study aimed to investigate the mechanism underlying the progression of HCC and to identify recurrence-related biomarkers.

Methods
We first analyzed 132 HCC patients with paired tumor and adjacent normal tissue samples from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). The expression profiles and clinical information of 372 HCC patients from The Cancer Genome Atlas (TCGA) database were next analyzed to further validate the DEGs, construct competing endogenous RNA (ceRNA) networks and discover the prognostic genes associated with recurrence. Finally, several recurrence-related genes were evaluated in two external cohorts, consisting of fifty-two and forty-nine HCC patients, respectively.

Results
With the comprehensive strategies of data mining, two potential interactive ceRNA networks were constructed based on the competitive relationships of the ceRNA hypothesis. The ‘upregulated’ ceRNA network consists of 6 upregulated lncRNAs, 3 downregulated miRNAs and 5 upregulated mRNAs, and the ‘downregulated’ network includes 4 downregulated lncRNAs, 12 upregulated miRNAs and 67 downregulated mRNAs. Survival analysis of the genes in the ceRNA networks demonstrated that 20 mRNAs were significantly associated with recurrence-free survival (RFS). Based on the prognostic mRNAs, a four-gene signature (ADH4, DNASE1L3, HGFAC and MELK) was established with the least absolute shrinkage and selection operator (LASSO) algorithm to predict the RFS of HCC patients, the performance of which was evaluated by receiver operating characteristic curves. The signature was also validated in two external cohort and displayed effective discrimination and prediction for the RFS of HCC patients.

Conclusions
In conclusion, the present study elucidated the underlying mechanisms of tumorigenesis and progression, provided two visualized ceRNA networks and successfully identified several potential biomarkers for HCC recurrence prediction and targeted therapies.
Oral candidal carriage and its association with dental carious lesions in asymptomatic adults: a cross-sectional study from the UAE
Authors: Al-Amad Suhail H. , Rahman Betul , Khalifa Nadia , Awad Manal A. 
Published: April 2021

AbstractBackgroundCandida’spotential association with dental caries has previously been reported in children. This research aimed at investigating the associations betweenCandidaspecies in whole saliva and dental and periodontal health indices in a sample of adult patients.MethodsA cross-sectional study involving 160 patients investigated the associations betweenCandidaspecies collected by oral rinse technique, and Decayed, Missing, and Filled Surfaces (DMFS), and periodontal health indices. Chi-square and Independent Samplest-test were used to assess the associations betweenCandidacarriage and confounding variables. Binary logistic regression was used to assess association strengths betweenCandidacarriage and DMFS, adjusted for socio-demographic variables, diabetes mellitus and plaque index.ResultsCandidacolonies were identified in 49 (30.6%) patients with CFUs ranging from 103to 105colonies per mL. The quantity ofCandidaCFUs increased with age (r = 0.200;p < 0.05). Among all dental and periodontal health indices, only DMFS was significantly associated with higher values ofCandidacarriage (p = 0.034), and this association was independent from sex, age, smoking, diabetes mellitus and plaque index (OR: 1.014; 95% CI 1.0–1.03;p = 0.048).ConclusionThe association betweenCandidaspecies in whole saliva and DMFS reported here supports an etiological role ofCandidain dental cariogenesis among adults.
Baseline audiological profiling of South African females with cervical cancer: an important attribute for assessing cisplatin-associated ototoxicity
Authors: Paken Jessica , Govender Cyril D. , Pillay Mershen , Ayele Birhanu T. , Sewram Vikash 
Published: April 2021

AbstractBackgroundCisplatin is a popular antineoplastic agent used to treat cervical cancer in women from low and middle-income countries. Cisplatin treatment is associated with ototoxicity, often resulting in hearing loss. In light of this, it is crucial to conduct baseline audiological assessments prior to treatment initiation in order to evaluate the extent of cisplatin-associated-ototoxicity. Additionally, the identification of inherent risk factors and hearing patterns in specific patient cohorts is needed, especially in South Africa, a middle-income country characterized by the quadruple burden of disease (Human Immunodeficiency Virus (HIV), Tuberculosis (TB), Diabetes and Hypertension).MethodsThis study aimed to describe a profile of risk factors and hearing in a cohort of females with cervical cancer before cisplatin treatment commenced. A descriptive study design that included 82 cervical cancer patients, who underwent audiological evaluation prescribed for ototoxicity monitoring was conducted.ResultsAll participants (n = 82) presented with risk factors (diabetes, hypertension, HIV, and antiretroviral therapy) for cisplatin ototoxicity and/or pre-existing sensorineural hearing loss. High-frequency tinnitus was the most common otological symptom experienced by 25 (31%) participants. Fifty-nine (72%) participants presented with normal hearing, twenty-two (27%) with a sensorineural hearing loss, and 36% were diagnosed with mild hearing loss. Abnormal Distortion Product Otoacoustic Emissions (DPOAE) findings were obtained bilaterally in two participants (2.4%), in the right ear only of another two (2.4%) participants and the left ear of three participants (3.7%). Most participants (94%) had excellent word recognition scores, demonstrating an excellent ability to recognize words within normal conversational levels under optimal listening conditions. Age was significantly associated with hearing loss at all thresholds. Among the co-morbidities, an HIV positive status significantly triggered hearing loss, especially at higher frequencies.ConclusionThis study demonstrated that South African females with cervical cancer present with various co-morbidities, which may predispose them to develop cisplatin-associated -ototoxic hearing loss. Identification of these co-morbidities and hearing loss is essential for the accurate monitoring of cisplatin toxicities. Appropriate management of these patients is pivotal to reduce the adverse effects that hearing impairment can have on an individual’s quality of life and to facilitate informed decision-making regarding the commencement of cisplatin chemotherapy.
Unapproved clinical trials in Russia: exception or norm?
Authors: Talantov Petr , Niyazov Ravil , Viryasova Galina , Dranitsyna Margarita , Yasny Ilya 
Published: April 2021

Abstract
Background
In modern Russia, any clinical investigation of a pharmaceutical for use in humans is subject to prior evaluation and approval by the Ministry of Health and its Central Ethics Committee. Despite this, some researchers and trial sponsors fail to comply, this is particularly true in case of the studies initiated by domestic sponsors or sponsor-investigators and published in Russian language medical journals. This exploratory research aims to discover whether it is a sporadic non-compliance with regulations or a common practice.

Methods
We searched the Russian language database eLIBRARY for the phrase ‘results of a randomised trial’. We selected publications reporting clinical trials and conducted in Russia. For each of the selected studies, we searched the state register of the approved clinical trials. We assessed whether (1) the investigational medicinal product was approved for marketing in Russia; (2) the therapeutic indications, posology, and administration method in the clinical trial were consistent with the approved labelling; (3) the issue of the journal included an advertisement of the medicinal product in question; and (4) the full description of the methodology corroborated that the clinical trial was randomised, as was stated in the title or abstract.

Results
Of the 26 selected articles, 22 reported the results of unauthorised clinical trials. Three of those trials were conducted in children. Twenty-one studies reported on data from unauthorised trials for investigational products approved for marketing in Russia. However, in nine cases, the therapeutic indications, posology, or administration method did not match the conditions indicated in the labelling. Moreover, in one case, the unauthorised trial included a drug therapy intervention where the active substance was not approved for use in any medicinal product marketed in Russia. In 14 of the 26 articles, the issue of the journal or the article itself contained an advertisement for the same medicinal product or, in one case, its manufacturer. All publications accompanied by advertisements claimed that the medicinal product in question was efficacious.

Conclusions
A substantial fraction of the clinical trials initiated by domestic sponsors and reported in Russian medical journals failed to obtain the mandatory prior evaluation and approval from the regulator. This can affect the rights and well-being of the study participants and the scientific validity of the studies.
The positive externalities of migrant-based TB control strategy in a Chinese urban population with internal migration: a transmission-dynamic modeling study
Authors: Yang Chongguang , Kang Jian , Lu Liping , Guo Xiaoqin , Shen Xin , Cohen Ted , Menzies Nicolas A. 
Published: April 2021

Abstract
Background
Large-scale rural-to-urban migration has changed the epidemiology of tuberculosis (TB) in large Chinese cities. We estimated the contribution of TB importation, reactivation of latent infection, and local transmission to new TB cases in Shanghai, and compared the potential impact of intervention options.

Methods
We developed a transmission dynamic model of TB for Songjiang District, Shanghai, which has experienced high migration over the past 25 years. We calibrated the model to local demographic data, TB notifications, and molecular epidemiologic studies. We estimated epidemiological drivers as well as future outcomes of current TB policies and compared this base-case scenario with scenarios describing additional targeted interventions focusing on migrants or vulnerable residents.

Results
The model captured key demographic and epidemiological features of TB among migrant and resident populations in Songjiang District, Shanghai. Between 2020 and 2035, we estimate that over 60% of TB cases will occur among migrants and that approximately 43% of these cases will result from recent infection. While TB incidence will decline under current policies, we estimate that additional interventions—including active screening and preventive treatment for migrants—could reduce TB incidence by an additional 20% by 2035.

Conclusions
Migrant-focused TB interventions could produce meaningful health benefits for migrants, as well as for young residents who receive indirect protection as a result of reduced TB transmission in Shanghai. Further studies to measure cost-effectiveness are needed to evaluate the feasibility of these interventions in Shanghai and similar urban centers experiencing high migration volumes.
Susceptibility loci for pancreatic cancer in the Brazilian population
Authors: Aoki Mateus Nóbrega , Stein Angelika , de Oliveira Jaqueline Carvalho , Chammas Roger , Uno Miyuki , Munhoz Francielle Boçon de Araújo , Marin Anelis Maria , Canzian Federico 
Published: April 2021

Abstract
Background
Pancreatic adenocarcinoma (PA) is a very aggressive cancer and has one of the poorest prognoses. Usually, the diagnosis is late and resistant to conventional treatment. Environmental and genetic factors contribute to the etiology, such as tobacco and alcohol consumption, chronic pancreatitis, diabetes and obesity. Somatic mutation in pancreatic cancer cells are known and SNP profile by GWAS could access novel genetic risk factors for this disease in different population context. Here we describe a SNP panel for Brazilian pancreatic cancer, together with clinical and epidemiological data.

Methods
78 pancreatic adenocarcinoma and 256 non-pancreatic cancer subjects had 25 SNPs genotyped by real-time PCR. Unconditional logistic regression methods were used to assess the main effects on PA risk, using allelic, co-dominant and dominant inheritance models.

Results
9 SNPs were nominally associated with pancreatic adenocarcinoma risk, with 5 of the minor alleles conferring protective effect while 4 related as risk factor. In epidemiological and clinical data, tobacco smoking, diabetes and pancreatitis history were significantly related to pancreatic adenocarcinoma risk. Polygenic risk scores computed using the SNPs in the study showed strong associations with PA risk.

Conclusion
We could assess for the first time some SNPs related with PA in Brazilian populations, a result that could be used for genetic screening in risk population such as familial pancreatic cancer, smokers, alcohol users and diabetes patients.
Impact of bronchoalveolar lavage lymphocytosis on the effects of anti-inflammatory therapy in idiopathic non-specific interstitial pneumonia, idiopathic pleuroparenchymal fibroelastosis, and unclassifiable idiopathic interstitial pneumonia
Authors: Yamagata Akira , Arita Machiko , Tachibana Hiromasa , Tokioka Fumiaki , Sugimoto Chikatoshi , Sumikawa Hiromitsu , Tanaka Tomonori , Yasui Hideki , Fujisawa Tomoyuki , Nakamura Yutaro , Suda Takafumi , Ishida Tadashi 
Published: April 2021

Abstract
Background
Idiopathic non-specific interstitial pneumonia (iNSIP), idiopathic pleuroparenchymal fibroelastosis (iPPFE), and unclassifiable idiopathic interstitial pneumonia (IIP) are IIPs with chronic fibrotic phenotypes, and unlike idiopathic pulmonary fibrosis, they have often been treated with anti-inflammatory drugs, including corticosteroids and immunosuppressants. However, the impact of bronchoalveolar lavage (BAL) lymphocytosis on the effects of anti-inflammatory therapy has never been evaluated. This study aimed to elucidate whether BAL lymphocytosis can be used to predict the efficacy of anti-inflammatory drugs for iNSIP, iPPFE, and unclassifiable IIP.

Methods
Japanese patients diagnosed with iNSIP, iPPFE, and unclassifiable IIP by multidisciplinary discussion were identified using the nationwide registry. Eligible patients were stratified into four groups with and without BAL lymphocytosis and anti-inflammatory therapy to compare overall survival (OS) and changes in lung function. BAL lymphocytosis was defined as a lymphocyte differential count > 15%, and the cut-off was corroborated by survival classification and regression tree analysis.

Results
Overall, 186 patients (37 iNSIP, 16 iPPFE, and 133 unclassifiable IIP) were analyzed. Limited to patients treated with anti-inflammatory drugs (n = 123), patients with BAL lymphocytosis had a better prognosis [hazard ratio (HR), 0.26; 95% confidence interval (CI), 0.11–0.63; P = 0.003], higher slope of forced vital capacity (FVC) % predicted for 2 years, and longer OS (log-rank test, P = 0.012) than those without BAL lymphocytosis. On multivariate analysis, BAL lymphocytosis (HR 0.31; 95% CI 0.13–0.75; P = 0.009) was a prognostic factor for OS, along with age and FVC % predicted. Conversely, for patients managed without anti-inflammatory therapy (n = 63), the presence or absence of BAL lymphocytosis had no prognostic value.

Conclusions
BAL lymphocytosis is associated with good outcomes in patients treated with anti-inflammatory drugs, but has no prognostic value when anti-inflammatory drugs are not used. BAL lymphocytosis may provide a predictive biomarker for identifying patients with iNSIP, iPPFE and unclassifiable IIP who are likely to benefit from anti-inflammatory drugs.
The effect of miR-539 regulating TRIAP1 on the apoptosis, proliferation, migration and invasion of osteosarcoma cells
Authors: Liu Huowen , Yang Min , Zhang Yufeng , Yang Zhiqiang , Chen Zhe , Xie Yuanlong , Peng Binglong , Cai Lin 
Published: April 2021

Abstract
Objective
The purpose of this study is to explore the effect of miRNA-539 on osteosarcoma (OS) and the underlying mechanism, so as to find a new method for early diagnosis and treatment of osteosarcoma.

Method
miRNA-539 mimics was transfected into osteosarcoma cells 143b and MG-63 and upregulated the expression of miR-539. QT-PCR was used to detect transfection efficacy. CCK-8 method was used to detect proliferation of 143b and MG-63 osteosarcoma cells and flow cytometry was used to detect the apoptosis of osteosarcoma cells 143b and MG-63. Wound-healing test and Transwell test were used to detect the migration and invasion ability of osteosarcoma cells. TRIAP1 was found to be the potential target gene of miRNA-539 by online bioinformatics software and the expression level of TRIAP1 in osteosarcoma cells overexpressing miRNA-539 was detected by qT-PCR. Western blot was used to detect the level of expression of TRIAP1 and its downstream genes (p53, p21, apaf1 and caspase9) in osteosarcoma cells 143b and MG63 transfected with miR-539 mimics or miR-539 mimics-NC. A model of osteosarcoma subcutaneously transplanted in nude mice was constructed to observe the effect of miRNA-539 on the growth rate of osteosarcoma in vivo.

Results
After transfection of miRNA-539 mimics in osteosarcoma cells 143b and MG63, the proliferation level, migration ability, and invasion ability of the osteosarcoma cells were significantly lower than that in the control group, and the apoptosis level was significantly higher than that in the control group (P < 0.01). The dual luciferase reporter confirmed that TRIAP1 was the target of miR-539, and the expression level of TRIAP1 in 143b and MG63 transfected with miRNA-539 mimics was proved to be significantly lower than that in the control group (P < 0.01).The western blot showed the expression of genes targeted by TRIAP1 was upregulated when the expression of TRIAP1 was downregulated. In vivo, the osteosarcoma growth rate in the miRNA-539 mimics group was significantly slower than that in the control group (P < 0.01).

Conclusions
MiRNA-539 may inhibit the cell proliferation, migration and invasion of osteosarcoma cells and promote the apoptosis of osteosarcoma cells by targeting on TRIAP1.
Cyproheptadine, an epigenetic modifier, exhibits anti-tumor activity by reversing the epigenetic silencing of IRF6 in urothelial carcinoma
Authors: Jou Yeong-Chin , Lin Guan-Ling , Lin Hon-Yi , Huang Wan-Hong , Chuang Yu-Ming , Lin Ru-Inn , Chen Pie-Che , Wu Shu-Fen , Shen Cheng-Huang , Chan Michael W. Y. 
Published: April 2021

Abstract
Background
Urothelial carcinoma (UC) is the second most common malignancy of the urinary system with high rate of recurrence, UC patients therefore needed to be treated with surgery followed by chemotherapy. Development of novel therapeutics with minimal side-effect is an urgent issue. Our previous study showed that cyproheptadine (CPH), an anti-histamine, exhibited antitumor activity in UC in vitro and in an xenograft model. However, the molecular mechanism of how CPH inhibits tumor progression is not fully understood.

Methods
Genes that were upregulated after treatment with CPH in UC cells, were examined by RNA-Seq. Real-time quantitative PCR (RT-qPCR) was employed to detect IRF6 expression while COBRA assay and bisulphite pyrosequencing were used to examine promoter methylation of IRF6. Enrichment of total H3K27 acetylation and H3K4 mono-methylation were detected by western blotting. Colony formation and flow cytometry were used to examine proliferation and apoptosis in UC cells overexpressed or depleted with IRF6. Nude mice xenograft model was used to examine the effect of IRF6 in UC.

Results
Our result showed that several genes, including IRF6 were upregulated after treatment with CPH in BFTC905 UC cells. Further experiments found that treatment of CPH could restore the expression of IRF6 in several other UC cell lines, probably due to promoter hypomethylation and enrichment of H3K27 acetylation and H3K4 mono-methylation. These results may be due to the fact that CPH could alter the activity, but not the expression of epigenetic modifiers. Finally, re-expression of IRF6 in UC inhibited tumor growth in vitro and in an xenograft mouse model, by inducing apoptosis.

Conclusion
In conclusion, our results suggested that CPH may be an epigenetic modifier, modulating the expression of the potential tumor suppressor IRF6, in inhibiting tumor growth in UC.
Needs and resources of people with type 2 diabetes in peri-urban Cochabamba, Bolivia: a people-centred perspective
Authors: Leyns Christine Cécile , Couvreur Niek , Willems Sara , Van Hecke Ann 
Published: April 2021

Abstract
Background
The rising prevalence of type 2 diabetes results in a worldwide public healthcare crisis, especially in low- and middle-income countries (LMICs) with unprepared and overburdened health systems mainly focused on infectious diseases and maternal and child health. Studies regarding type 2 diabetes in LMICs describe specific interventions ignoring a comprehensive analysis of the local factors people see influential to their health. This study aims to meet this research gap by exploring what people with type 2 diabetes in Bolivia need to maintain or improve their health, how important they perceive those identified needs and to what extent these needs are met.

Methods
From March until May 2019, 33 persons with type 2 diabetes from three periurban municipalities of the department of Cochabamba participated in this study. The concept mapping methodology by Trochim, a highly structured qualitative brainstorming method, was used to generate and structure a broad range of perspectives on what the participants considered instrumental for their health.

Results
The brainstorming resulted in 156 original statements condensed into 72 conceptually different needs and resources, structured under nine conceptual clusters and four action domains. These domains illustrated with vital needs were: (1) self-management with use of plants and the possibility to measure sugar levels periodically; (2) healthcare providers with the need to trust and receive a uniform diagnosis and treatment plan; (3) health system with opportune access to care and (4) community with community participation in health and safety, including removal of stray dogs.

Conclusions
This study identifies mostly contextual factors like low literacy levels, linguistic problems in care, the need to articulate people’s worldview including traditional use of natural remedies with the Bolivian health system and the lack of expertise on type 2 diabetes by primary health care providers. Understanding the needs and structuring them in different areas wherein action is required serves as a foundation for the planning and evaluation of an integrated people centred care program for people with type 2 diabetes. This participative method serves as a tool to implement the often theoretical concept of integrated people centred health care in health policy and program development.