bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALKBH5-mediated m6A demethylation of lncRNA PVT1 plays an oncogenic role in osteosarcoma
Authors: Chen Shuo , Zhou Liwu , Wang Yang 
Published: January 2020

Abstract
Background
Osteosarcoma (OS) is one of the most common malignant bone tumors. Plasmacytoma variant translocation 1 (PVT1) is a well-known oncogenic long noncoding RNA (lncRNA). However, to date, the regulatory mechanism of PVT1 upregulation in OS remains unknown.

Methods
qRT-PCR was carried out to test the expression level of PVT1 and ALKBH5. RNA immunoprecipitation (RIP) and RNA pull-down assays were performed to detect the interaction of PVT1 with ALKBH5 and YTHDF2. Methylated RNA immune-precipitation (MeRIP) was used to examine the N6-methyladenosine (m6A) modification of PVT1 transcript.

Results
In this study, we found that PVT1 expression was upregulated in OS tissues and cells and significantly related with clinical stage, tumor size, and prognosis of patients with OS. Further investigation revealed that N6-methyladenosine (m6A) demethylase ALKBH5 could associate with PVT1 and suppress its degradation. ALKBH5 decreased the m6A modification of PVT1, thus inhibiting the binding of reader protein YTHDF2 in PVT1. Functionally, ALKBH5-mediated PVT1 upregulation promoted the OS cell proliferation in vitro and tumor growth in vivo.

Conclusions
Our study suggests that ALKBH5-mediated m6A modification of PVT1 contributes to OS tumorigenesis.
Baicalin reverses radioresistance in nasopharyngeal carcinoma by downregulating autophagy
Authors: Wang Cong , Yang Yinli , Sun Lining , Wang Jing , Jiang Zhansheng , Li Yanwei , Liu Dongying , Sun Haiyan , Pan Zhanyu 
Published: January 2020

Abstract
Background
Radiation resistance is the main cause of recurrence after radiotherapy, and increased autophagy after radiotherapy is related to radiotherapy resistance. This study aims to investigate the reversal effect of baicalin on radioresistance and its related mechanism.

Methods
CCK-8 and flow cytometry were used to detect the effect of proliferation and apoptosis by baicalin. Clone formation test was used to verify the effect of baicalin radiosensitization. Western blot analysis and electron microscopy were employed to observe the effect of baicalin on autophagy.

Results
Compared with the radiation therapy (RT) group, the RT combined baicalin (RT + BA) group showed a significantly low 2 Gy survival fraction of radiation therapy (P < 0.05). LC3-II protein expression in the RT group was significantly higher than which in the RT + BA group (P < 0.05). Electron microscopy showed that more autophagic vacuoles were observed in the RT group than those in the RT + BA group.

Conclusions
Overall, baicalin can reverse the radioresistance of human nasopharyngeal carcinoma CNE-2R cells by downregulating RT-enhanced autophagy.
A novel chalcone derivative has antitumor activity in melanoma by inducing DNA damage through the upregulation of ROS products
Authors: Li Keke , Zhao Shuang , Long Jing , Su Juan , Wu Lisha , Tao Juan , Zhou Jianda , Zhang JiangLin , Chen Xiang , Peng Cong 
Published: January 2020

Abstract
Background
Melanoma is one of the most aggressive tumors with the remarkable characteristic of resistance to traditional chemotherapy and radiotherapy. Although targeted therapy and immunotherapy benefit advanced melanoma patient treatment, BRAFi (BRAF inhibitor) resistance and the lower response rates or severe side effects of immunotherapy have been observed, therefore, it is necessary to develop novel inhibitors for melanoma treatment.

Methods
We detected the cell proliferation of lj-1-59 in different melanoma cells by CCK 8 and colony formation assay. To further explore the mechanisms of lj-1-59 in melanoma, we performed RNA sequencing to discover the pathway of differential gene enrichment. Western blot and Q-RT-PCR were confirmed to study the function of lj-1-59 in melanoma.

Results
We found that lj-1-59 inhibits melanoma cell proliferation in vitro and in vivo, induces cell cycle arrest at the G2/M phase and promotes apoptosis in melanoma cell lines. Furthermore, RNA-Seq was performed to study alterations in gene expression profiles after treatment with lj-1-59 in melanoma cells, revealing that this compound regulates various pathways, such as DNA replication, P53, apoptosis and the cell cycle. Additionally, we validated the effect of lj-1-59 on key gene expression alterations by Q-RT-PCR. Our findings showed that lj-1-59 significantly increases ROS (reactive oxygen species) products, leading to DNA toxicity in melanoma cell lines. Moreover, lj-1-59 increases ROS levels in BRAFi -resistant melanoma cells, leading to DNA damage, which caused G2/M phase arrest and apoptosis.

Conclusions
Taken together, we found that lj-1-59 treatment inhibits melanoma cell growth by inducing apoptosis and DNA damage through increased ROS levels, suggesting that this compound is a potential therapeutic drug for melanoma treatment.
Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy
Authors: Ren Daixi , Hua Yuze , Yu Boyao , Ye Xin , He Ziheng , Li Chunwei , Wang Jie , Mo Yongzhen , Wei Xiaoxu , Chen Yunhua , Zhou Yujuan , Liao Qianjin , Wang Hui , Xiang Bo , Zhou Ming , Li Xiaoling , Li Guiyuan , Li Yong , Zeng Zhaoyang , Xiong Wei 
Published: January 2020

AbstractImmune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in a variety of tumors, but resistance during treatment is a major issue. In this review, we describe the utility of PD-L1 expression levels, mutation burden, immune cell infiltration, and immune cell function for predicting the efficacy of PD-1/PD-L1 blockade therapy. Furthermore, we explore the mechanisms underlying immunotherapy resistance caused by PD-L1 expression on tumor cells, T cell dysfunction, and T cell exhaustion. Based on these mechanisms, we propose combination therapeutic strategies. We emphasize the importance of patient-specific treatment plans to reduce the economic burden and prolong the life of patients. The predictive indicators, resistance mechanisms, and combination therapies described in this review provide a basis for improved precision medicine.
Application of antigen presenting cell-targeted nanovaccine delivery system in rhabdovirus disease prophylactics using fish as a model organism
Authors: Zhang Chen , Wang Gao-Xue , Zhu Bin 
Published: January 2020

AbstractBackgroundTargeted delivery of virus-associated antigens to professional antigen-presenting cells (APCs) is considered as an efficient strategy to enhance the pyrophytic effect of vaccines against rhabdovirus disease.Materials and methodsIn this study, we constructed a targeted carbon nanotubes-based vaccine deliver system (SWCNTs-MG) which can recognize the signature receptor (mannose) of APCs. An environmentally and economically important disease called spring viremia of carp (SVC) was studied as a model to evaluate the feasibility of single-walled carbon nanotubes (SWCNTs) conjugated with mannosylated antigen for rhabdovirus prevention.ResultsResults showed that SWCNTs-MG could cross into fish body and present to internal immune-related tissues through gill, muscle and intestine within 6 h immersed vaccination. With further modification of mannose moiety, the obtained nanovaccine showed enhanced uptake by carp macrophages and immune-related tissues, which would then trigger strong immune responses against spring viremia of carp virus (SVCV) infection. Moreover, the survival rate of fish vaccinated with SWCNTs-MG (30 mg/L) was 63.5% after SVCV infection, whereas it was 0% for the control group.ConclusionThis study not only provide a theoretical basis and research template for the application of targeted nanovaccine system in aquatic animals, but also play an important role in supporting development of healthy aquaculture and ensuring the safety of aquatic products and ecology.
Health-related quality of life in adolescents with persistent pain and the mediating role of self-efficacy: a cross-sectional study
Authors: Grasaas Erik , Helseth Sølvi , Fegran Liv , Stinson Jennifer , Småstuen Milada , Haraldstad Kristin 
Published: January 2020

Abstract
Background
Persistent pain has a high prevalence among adolescents. Pain has been shown to reduce all aspects of the adolescent’s health-related quality of life (HRQOL). In adult patients with pain, self-efficacy has been shown to mediate the relationship between pain intensity, disability and depression. However, little is known about whether self-efficacy acts as a mediating variable in the relationship between persistent pain and HRQOL sub-scale scores in a school-based population of adolescents.

Objectives
To describe the experience of pain, HRQOL and self-efficacy, and to explore the association between pain intensity, general self-efficacy and HRQOL in adolescents with persistent pain by testing self-efficacy as a possible mediator.

Methods
The study participants were 78 adolescents with persistent pain, aged 16–19 years, who were recruited from five high schools in southern Norway. All participants completed an electronic survey consisting of the Lubeck Pain Questionnaire, which included a visual analogue scale (VAS) measuring pain intensity, the General Self-Efficacy Scale (GSE) and the KIDSCREEN-52 Questionnaire measuring HRQOL. Statistical analyses were conducted using the PROCESS macro for SPSS developed by Andrew Hayes.

Results
All participants reported pain in multiple locations, of which the head was most common (88.5%). Mean (SD) pain intensity score of the participants was 5.4 (1.8). The study sample had poor HRQOL, with mean (SD) scores for several sub-scales ranging from 45.2 (21.0) to 91.0 (13.3) on a 0–100 scale. The associations between pain intensity and the HRQOL sub-scales of physical well-being, psychological well-being, mood, self-perception, autonomy and school environment were mediated by self-efficacy. The highest degree of mediation and, thus, the largest indirect effect was estimated for the HRQOL sub-scale physical well-being (67.2%).

Conclusions
This school-based sample of adolescents with persistent pain had impaired HRQOL. Up to 67% of the reduction in the HRQOL sub-scale scores for physical well-being, psychological well-being, mood, self-perception, autonomy and school environment could be explained by the mediating variable self-efficacy. Thus, future pain-management interventions that aim to increase HRQOL in school-based populations of adolescents with persistent pain should consider promoting self-efficacy and providing more targeted interventions.

Trial registration
ClinicalTrials.gov ID NCT03551977.
The quality of life of the patients with diabetes type 2 using EQ-5D-5 L in Birjand
Authors: Abedini Mohammad Reza , Bijari Bita , Miri Zahra , Shakhs Emampour Fatemeh , Abbasi Ali 
Published: January 2020

AbstractBackgroundDue to high prevalence of diabetes and its complications, evaluating of the patients’ quality of life is critical. EQ-5D-5 L is a valid tool for assessing the quality of life in chronic diseases including diabetes. The present study conducted to illustrate the quality of life for the patients who referred to the Diabetes clinic and determine its relationship with their demographic and clinical characteristics in Birjand in 2017.MethodsIn this cross-sectional study, 300 patients with type 2 diabetes were selected through a systematic sampling in 2017. Data were collected using a checklist including patients’ demographic, clinical and laboratory information and the EQ-5D-5 L. Data were entered the SPSS (22) software, analyzed by independent sample T-test, ANOVA, Chi-Square and logistic regression tests. Statistical significance was inferred at α = 0.05.ResultsMean age for the participants was 58.1 ± 9.6 years. The mean score for the quality of life based on the EQ-5D-5 L and VAS scale were 0.89 ± 0.13 and 65.22 ± 9.32, respectively. Moderate and severe problems were found in the anxiety/depression dimensions in 12% of the patients, while these numbers for the presence of pain/discomfort and mobility were slightly higher (13.7 and 13.6%, respectively). The mean scores for quality of life and VAS were significantly higher in the men, employed and patients < 50 years age.ConclusionThe quality of life for the type 2 diabetes patients is affected by numerous factors including sex, occupation, duration of the disease and the presence of complications such as neuropathy and nephropathy.
Prognostic value of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma
Authors: Yang Qiankun , Chen Tong , Yao Zhongxiang , Zhang Xiaojing 
Published: January 2020

AbstractBackgroundThis study aimed to evaluate the clinical significance of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma.MethodsThe clinical data of 133 osteosarcoma patients between January 2011 and February 2018 in our hospital was retrospectively collected and analyzed. NPS was calculated from four parameters, including serum albumin level, serum total cholesterol (TC), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR). Patients were divided into three groups (group 1-3) based on NPS. The relationships between NPS and clinical features, overall survival (OS), and progression-free survival (PFS) were analyzed. Two prediction models based on NPS and clinical parameters were developed: clinical parameters model (model A), and the combined model of NPS and clinical parameters (model B). Their predictive performances were further evaluated and compared.ResultsThe median follow-up time of this cohort was 46.0 (range, 5–75) months, while the median OS and PFS was 40 (range, 5–75) months and 36 (range, 5–71) months, respectively. NPS was significantly correlated with gender, tumor location, Enneking stage, pathological fracture, local recurrence, and metastasis (allP< 0.05). Variables of NPS, Enneking stage, local recurrence, metastasis, and NLR were confirmed as independent prognostic factors for OS and PFS by univariate and multivariate Cox analysis. Prediction model B obtained larger AUCs for OS and PFS and showed better consistency between nomogram-predicted and actual survival than that of model A at the follow-up time of 1-, 3-, and 5-year.ConclusionsNPS was a novel, reliable, and multidimensional prognostic scoring system with favorable predictive performance for patients with osteosarcoma.
A clinical-radiomics nomogram for the preoperative prediction of lymph node metastasis in colorectal cancer
Authors: Li Menglei , Zhang Jing , Dan Yibo , Yao Yefeng , Dai Weixing , Cai Guoxiang , Yang Guang , Tong Tong 
Published: January 2020

Abstract
Background
Accurate lymph node metastasis (LNM) prediction in colorectal cancer (CRC) patients is of great significance for treatment decision making and prognostic evaluation. We aimed to develop and validate a clinical-radiomics nomogram for the individual preoperative prediction of LNM in CRC patients.

Methods
We enrolled 766 patients (458 in the training set and 308 in the validation set) with clinicopathologically confirmed CRC. We included nine significant clinical risk factors (age, sex, preoperative carbohydrate antigen 19-9 (CA19-9) level, preoperative carcinoembryonic antigen (CEA) level, tumor size, tumor location, histotype, differentiation and M stage) to build the clinical model. We used analysis of variance (ANOVA), relief and recursive feature elimination (RFE) for feature selection (including clinical risk factors and the imaging features of primary lesions and peripheral lymph nodes), established classification models with logistic regression analysis and selected the respective candidate models by fivefold cross-validation. Then, we combined the clinical risk factors, primary lesion radiomics features and peripheral lymph node radiomics features of the candidate models to establish combined predictive models. Model performance was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Finally, decision curve analysis (DCA) and a nomogram were used to evaluate the clinical usefulness of the model.

Results
The clinical-primary lesion radiomics-peripheral lymph node radiomics model, with the highest AUC value (0.7606), was regarded as the candidate model and had good discrimination and calibration in both the training and validation sets. DCA demonstrated that the clinical-radiomics nomogram was useful for preoperative prediction in the clinical environment.

Conclusion
The present study proposed a clinical-radiomics nomogram with a combination of clinical risk factors and radiomics features that can potentially be applied in the individualized preoperative prediction of LNM in CRC patients.
Oligohydramnios: a prospective study of fetal, neonatal and maternal outcomes in low-middle income countries
Authors: Figueroa Lester , McClure Elizabeth M. , Swanson Jonathan , Nathan Robert , Garces Ana L. , Moore Janet L. , Krebs Nancy F. , Hambidge K. Michael , Bauserman Melissa , Lokangaka Adrien , Tshefu Antoinette , Mirza Waseem , Saleem Sarah , Naqvi Farnaz , Carlo Waldemar A. , Chomba Elwyn , Liechty Edward A. , Esamai Fabian , Swanson David , Bose Carl L. , Goldenberg Robert L. 
Published: January 2020

Abstract
Background
Oligohydramnios is a condition of abnormally low amniotic fluid volume that has been associated with poor pregnancy outcomes. To date, the prevalence of this condition and its outcomes has not been well described in low and low-middle income countries (LMIC) where ultrasound use to diagnose this condition in pregnancy is limited. As part of a prospective trial of ultrasound at antenatal care in LMICs, we sought to evaluate the incidence of and the adverse maternal, fetal and neonatal outcomes associated with oligohydramnios.

Methods
We included data in this report from all pregnant women in community settings in Guatemala, Pakistan, Zambia and the Democratic Republic of Congo (DRC) who received a third trimester ultrasound as part of the First Look Study, a randomized trial to assess the value of ultrasound at antenatal care. Using these data, we conducted a planned secondary analysis to compare pregnancy outcomes of women with to those without oligohydramnios. Oligohydramnios was defined as measurement of an Amniotic Fluid Index less than 5 cm in at least one ultrasound in the third trimester. The outcomes assessed included maternal morbidity and fetal and neonatal mortality, preterm birth and low-birthweight. We used pairwise site comparisons with Tukey-Kramer adjustment and multivariable logistic models using general estimating equations to account for the correlation of outcomes within cluster.

Results
Of 12,940 women enrolled in the clusters in Guatemala, Pakistan, Zambia and the DRC in the First Look Study who had a third trimester ultrasound examination, 87 women were diagnosed with oligohydramnios, equivalent to 0.7% of those studied. Prevalence of detected oligohydramnios varied among study sites; from the lowest of 0.2% in Zambia and the DRC to the highest of 1.5% in Pakistan. Women diagnosed with oligohydramnios had higher rates of hemorrhage, fetal malposition, and cesarean delivery than women without oligohydramnios. We also found unfavorable fetal and neonatal outcomes associated with oligohydramnios including stillbirths (OR 5.16, 95%CI 2.07, 12.85), neonatal deaths < 28 days (OR 3.18, 95% CI 1.18, 8.57), low birth weight (OR 2.10, 95% CI 1.44, 3.07) and preterm births (OR 2.73, 95%CI 1.76, 4.23). The mean birth weight was 162 g less (95% CI -288.6, − 35.9) with oligohydramnios.

Conclusions
Oligohydramnos was associated with worse neonatal, fetal and maternal outcomes in LMIC. Further research is needed to assess effective interventions to diagnose and ultimately to reduce poor outcomes in these settings.

Trial registration
NCT01990625.
Developing of a new guideline for improving birth experiences among Iranian women: a mixed method study protocol
Authors: Ghanbari-Homayi Solmaz , Fardiazar Zahra , Mohammad-Alizadeh-Charandabi Sakineh , Asghari Jafarabadi Mohammad , Mohamadi Eesa , Meedya Shahla , Mirghafourvand Mojgan 
Published: January 2020

AbstractBackgroundThe childbirth experience has significant effects on the life of the mother and family. However, there are no Iranian studies which evaluate and measure women’s childbirth experiences to provide accurate data on this important matter. The aim of this study is to develop a new guideline to improve women’s childbirth experiences by meeting their needs and expectations.Methods/designThe present study will use the mixed method with the explanatory sequential approach. Phase one is a cross-sectional survey with random cluster sampling of the health centers in Tabriz. Eight hundred primiparous women will be selected to measure their childbirth experiences and predictors factors. Phase two is a qualitative study to explore women’s perceptions of the aspects and determinants of the childbirth experience. Phase two participants will be selected using purposive sampling from the women who participated in phase one. Phase three involves developing a new guideline to improve women’s childbirth experiences. The new guideline will be developed based on the following elements: a) the results of the qualitative and quantitative data from phase one and two, b) a review of the related literature, and c) expert opinions that have been collected using the Delphi technique.DiscussionBy exploring women’s childbirth experiences and the influencing factors, a culturally sensitive evidence-based guideline can be developed. The provision of the evidence-based guideline resulting from this study might be effective in improving the quality care of the services for pregnant women.Ethical codeIR.TBZMED.REC.1396.786.