bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prioritization of interventions in pursuit of maternal health policy objectives to mitigate stillbirth risks. An exploratory qualitative study at subnational level in Uganda
Authors: Ssegujja Eric , Ddumba Isaac , Andipartin Michelle 
Published: January 2021

Abstract
Background
Global calls for renewed efforts to address stillbirth burden highlighted areas for policy and implementation resulting in national level translations. Information regarding adapted strategies to effect policy objectives into service delivery by frontline health workers remains scanty especially at subnational level. The study explored strategies prioritized to mitigate stillbirth risk in the context of operationalizing recommendations from the global campaigns at a subnational level in Uganda.

Methods
A cross-sectional qualitative exploratory study was conducted among a purposively selected sample of sixteen key informants involved in delivery of maternal and child health services in Mukono district. Analysis followed thematic content analysis deductively focusing on those policy priorities highlighted in the global stillbirth campaigns and reflected at the national level in the different guidelines. Results.
Interventions to address stillbirth followed prioritization of service delivery aspects to respond to identified gaps. Efforts to increase uptake of family planning services for example included offering it at all entry points into care with counseling forming part of the package following stillbirth. Referrals were streamlined by focusing on addressing delays from the referring entity while antenatal care attendance was boosted through provision of incentives to encourage mothers to comply. Other prioritized aspects included perinatal death audits and improvements in data systems while differentiated care focused on aligning resources to support high risk mothers. This was in part influenced by the limited resources and skills which made health workers to adapt routine to fit implementation context.

Conclusions
The resource availability determined aspects of policy to prioritize while responding to stillbirth risk at subnational level by frontline health workers. Their understanding of risk, feasibility of implementation and the desire for optimal health systems performance worked to define the nature of services delivered calling for purposeful consideration of resource availability and implementation context while prioritizing stillbirth reduction at subnational level.
Beyond weight: examining the association of obesity with cardiometabolic related inpatient costs among Canadian adults using linked population based survey and hospital administrative data
Authors: Gupta Neeru , Sheng Zihao 
Published: January 2021

Abstract
Background
The global population has transitioned to one where more adults are living with obesity than are underweight. Obesity is associated with the development of cardiometabolic diseases and widely attributed to increased hospital resource use; however, empirical evidence is limited regarding obesity prevention to support hospital cost containment. This study aims to test for obesity in predicting hospitalization costs for cardiometabolic conditions among the Canadian population aged 45 and over.

Methods
Data from the 2007−2011 Canadian Community Health Survey were linked to eight years of hospital discharge records. A cohort was identified of inpatients admitted for diabetes, hypertension, and other cardiometabolic diseases. Multiple linear regressions were used to investigate the association between obesity status and inpatient costs, controlling for sociodemographic and behavioural factors.

Results
The target cohort included 23,295 admissions for cardiometabolic diseases. Although inflation-adjusted inpatient costs generally increased over time, compared with the non-obese group, living with obesity was not a significant predictor of differences in cardiometabolic-related resource use (0.972 [95% CI: 0.926–1.021]). Being female and rural residence were found to be protective factors.

Conclusions
Obesity was not found in this study to be independently linked to higher cardiometabolic hospitalization costs, suggesting that actions to mitigate disease progression in the population may be more beneficial than simply promoting weight loss. Results amplified the need to consider gender and urbanization when formulating which levers are most amenable to adoption of healthy lifestyles to reduce impacts of obesogenic environments to the healthcare system.
Apolipoprotein C1 stimulates the malignant process of renal cell carcinoma via the Wnt3a signaling
Authors: Jiang Hao , Tang Jing-Yuan , Xue Dong , Chen Yi-Meng , Wu Ting-Chun , Zhuang Qian-Feng , He Xiao-Zhou 
Published: January 2021

Abstract
Background
Renal cell carcinoma (RCC) is a clinically common tumor in the urinary system, showing an upward trend of both incidence and mortality. Apolipoprotein C1 (APOC1) has been identified as a vital regulator in tumor progression. This study aims to uncover the biological function of APOC1 in RCC process and the underlying mechanism.

Methods
Differential levels of APOC1 in RCC samples and normal tissues in a downloaded TCGA profile and clinical samples collected in our center were detected by quantitative reverse transcription PCR (qRT-PCR). The prognostic value of APOC1 in RCC was assessed by depicting Kaplan–Meier survival curves. After intervening APOC1 level by transfection of sh-APOC1 or oe-APOC1, changes in phenotypes of RCC cells were examined through CCK-8, colony formation, Transwell assay and flow cytometry. Subsequently, protein levels of EMT-related genes influenced by APOC1 were determined by Western blot. The involvement of the Wnt3a signaling in APOC1-regulated malignant process of RCC was then examined through a series of rescue experiments. Finally, a RCC xenograft model was generated in nude mice, aiming to further clarify the in vivo function of APOC1 in RCC process.

Results
APOC1 was upregulated in RCC samples. Notably, its level was correlated to overall survival of RCC patients, displaying a certain prognostic value. APOC1 was able to stimulate proliferative, migratory and invasive abilities in RCC cells. The Wnt3a signaling was identified to be involved in APOC1-mediated RCC process. Notably, Wnt3a was able to reverse the regulatory effects of APOC1 on RCC cell phenotypes. In vivo knockdown of APOC1 in xenografted nude mice slowed down the growth of RCC.

Conclusions
APOC1 stimulates the malignant process of RCC via targeting the Wnt3a signaling.
Ceramide kinase mediates intrinsic resistance and inferior response to chemotherapy in triple‐negative breast cancer by upregulating Ras/ERK and PI3K/Akt pathways
Authors: Zhu Shan , Xu Yulin , Wang Lijun , Liao Shichong , Wang Yuan , Shi Manman , Tu Yi , Zhou Yurong , Wei Wen 
Published: January 2021

Abstract
Background
Clinical management of triple-negative breast cancer (TNBC) patients remain challenging because of the development of chemo-resistance. Identification of biomarkers for risk stratification of chemo-resistance and therapeutic decision-making to overcome such resistance is thus necessary.

Methods
Retrospective analysis was performed to identify potential stratification biomarkers. The levels of ceramide kinase (CERK) was determined in breast cancer patients. The roles of CERK and its downstream signaling pathways were analysed using cellular and biochemical assays.

Results
CERK upregulation was identified as a biomarker for chemotherapeutic response in TNBC. A > 2-fold change in CERK (from tumor)/CERK (from normal counterpart) was significantly associated with chemo-resistance (OR = 2.66, 95% CI 1.18–7.34), P = 0.04. CERK overexpression was sufficient to promote TNBC growth and migration, and confer chemo-resistance in TNBC cell lines, although this resistance could be overcome via CERK inhibition. Mechanistic studies suggest that CERK mediates intrinsic resistance and inferior response to chemotherapy in TNBC by regulating multiple oncogenic pathways such as Ras/ERK, PI3K/Akt/mTOR, and RhoA.

Conclusions
Our work provides an explanation for the heterogeneity of chemo-response across TNBC patients and demonstrates that CERK inhibition offers a therapeutic strategy to overcome treatment resistance.
RETRACTED ARTICLE: Transcription elongation factor A-like 7, regulated by miR-758-3p inhibits the progression of melanoma through decreasing the expression levels of c-Myc and AKT1
Authors: Liu Xilin , Song Xianji , Li Hong 
Published: January 2021

Abstract
Background
Ectopic expression of transcription elongation factor A (SII)-like 7 (TCEAL7) has been observed in several kinds of cancers, but its role in melanoma is still unclear. This study was carried out to investigate TCEAL7 role in melanoma progression, and uncover the underlying mechanisms.

Methods
TCEAL7 expression levels in melanoma tissues and cells were determined by using real-time quantitative PCR (RT-PCR) and western blotting. CCK-8, transwell chambers, flow cytometry, starch assay and tumorigenesis assay were applied to detect cell growth, invasion, apoptosis, migration and tumorigenesis, respectively.

Results
A low expression level of TCEAL7 was observed in melanoma tissues and cells, which was associated with malignant clinical process and poor prognosis. TCEAL7 negatively modulated AKT1, AKT2, c-Myc, N-cadherin and PCNA expression and inhibited cancer progression via decreasing AKT1 and c-Myc levels. In addition, TCEAL7 was negatively modulated by miR-758-3p which promoted melanoma progression. Moreover, overexpression of TCEAL7 abolished miR-758-3p role in promoting melanoma progression.

Conclusion
This study demonstrated that TCEAL7, regulated by miR-758-3p inhibited melanoma progression through decreasing the expression levels of c-Myc and AKT1.
Decreased expression of METTL14 predicts poor prognosis and construction of a prognostic signature for clear cell renal cell carcinoma
Authors: Wang Yi , Cong Rong , Liu Shouyong , Zhu Bingye , Wang Xing , Xing Qianwei 
Published: January 2021

AbstractBackgroundMETTL14, as one of N6-methyladenosine (m6A) related genes, has been found to be associated with promoting tumorigenesis in different types of cancers. This study was aimed to investigate the prognostic value of METTL14 in clear cell renal cell carcinoma (ccRCC).MethodsWe collected ccRCC patients’ clinicopathological parameters information and 13 m6A related genes expression from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were conducted to investigate whether METTL14 could serve as an independent factor correlated with overall survival (OS). Gene Set Enrichment Analysis (GSEA) was carried out to identify METTL14-related signaling pathways. Moreover, a risk score (RS) was calculated to predict the prognosis of ccRCC. Quantitative real-time PCR (qRT-PCR) was also utilized to verify the expression of METTL14 in clinical specimens.ResultsDifferently expressed m6A related genes were identified between ccRCC tissues and normal tissues. Therein, METTL14 was lowly expressed in ccRCC tissues and verified by qRT-PCR (all p < 0.01). Survival analysis indicated that high expression of METTL14 was associated with better OS (p = 1e−05). GSEA results revealed that high METTL14 expression was enriched in ERBB pathway, MAPK pathway, mTOR pathway, TGF-β pathway and Wnt pathway. Moreover, METTL14 was proved to be an independent prognostic factor by means of univariate and multivariate Cox regression analyses. Nomogram integrating both the METTL14 expression and clinicopathologic variables was also established to provide clinicians with a quantitative approach for predicting survival probabilities of ccRCC. Furthermore, a METTL14-based riskscore (RS) was developed with significant OS (p = 6.661e−16) and increased AUC of 0.856. Besides, significant correlated genes with METTL14 were also provided.ConclusionsOur results indicated that METTL14 could serve as a favorable prognostic factor for ccRCC. Moreover, this study also provided a prognostic signature to predict prognosis of ccRCC and identified METTL14-related signaling pathways.
Evaluation of cardiovascular risk factors in patients with familial hypercholesterolemia from the North-Eastern area of Romania
Authors: Vlad Cristiana-Elena , Foia Liliana , Florea Laura , Costache Irina-Iuliana , Covic Andreea , Popescu Roxana , Reurean-Pintilei Delia , Covic Adrian 
Published: January 2021

Abstract
Background
Familial hypercholesterolemia(FH) is one of the most frequent and important monogenic cholesterol pathologies. Traditional and non-traditional cardiovascular risk factors increase the prevalence of atherosclerotic cardiovascular disease(ASCVD) in this population. The aims of the study were: (a) to identify FH patients in the North-Eastern part of Romania and to analyze demographic, clinical and paraclinical data (b) to evaluate the risk of new cardiovascular events at follow-up in FH patients stratified by lipid-lowering agents.

Methods
This first prospective study in the North-Eastern part of Romania was carried out between October 2017 and October 2019; out of 980 patients with dyslipidemia evaluated with the Dutch Lipid Network(DLCN) and Simon Broome(SM) scores, 61 patients with DLCN score above 3 and possible/probable FH(SM score) were included.

Results
Nine hundred-eighty patients were examined and 61 (6.2%) were received the clinical diagnosis of FH. The mean age was 48.5±12.5 years, with more female patients than male patients (63.9% versus 36%). Hypertension was the main cardiovascular risk factor for both genders, followed by physical inactivity and obesity for the female group and active smoking for the male group. The measured DLCN score recorded: “possible” FH identified in 39.4%, “probable” FH in 45.9% and “definite” FH in 14.7%. The effective lipid-lowering drugs used were statin alone and statin in association with fenofibrate, which improved both the lipid profile values and the subclinical atherosclerosis markers (ankle-brachial index, carotid intima-media thickness and high-sensitivity C-reactive protein). New ASCVDs that emerged during the study were most commonly represented by coronary heart disease and stroke. At the same time, the new cardiovascular events were delayed in patients receiving the lipid-lowering drugs, without significant differences between them.

Conclusions
In patients with suspected FH, the lipid-lowering agents during the follow-up period delayed the new cardiovascular events, yet failed to reach the goals proposed by the guidelines.
The impact of family planning on maternal mortality in Indonesia: what future contribution can be expected?
Authors: Utomo Budi , Sucahya Purwa Kurnia , Romadlona Nohan Arum , Robertson Annette Sachs , Aryanty Riznawaty Imma , Magnani Robert Joseph 
Published: January 2021

Abstract
Background
Although efforts to reduce high maternal mortality in countries such as Indonesia tend to focus on addressing health risks among pregnant women, family planning has been shown globally to reduce maternal mortality by reducing both total and higher-risk pregnancies. This article assesses past contributions of family planning to the reduction of maternal mortality in Indonesia and the potential future contribution toward achieving the 2030 SDG maternal mortality goal.

Methods
The study takes advantage of data from long series of population censuses and large-scale surveys that are available in few other low- and middle-income countries. We use the decomposition method suggested by (Matern Child Health J, 16:456–463, 2012) and regression-based policy simulations to estimate the number of maternal deaths averted during 1970–2017 due to contraceptive use and project potential future contributions to the year 2030.

Results
It is estimated that between 523,885 and 663,146 maternal deaths were averted from 1970 to 2017 due to contraceptive use, a 37.5–43.1% reduction. If the contraceptive prevalence rate (CPR) were to rise from 63% in 2017 to 70% in 2030 and unmet need for family planning were to fall to from 10 to 7%, an additional 34,621–37,186 maternal deaths would be averted, an 18.9–20.0% reduction. A 2030 CPR of 75% and unmet need for family planning of 5% would result in 51,971–54,536 maternal deaths being averted, a 28.4–29.4% reduction. However, the CPR growth rate would have to nearly double the 2000–2017 rate to reach 70% CPR by 2030 and more than triple to reach 75%. Achieving the most ambitious target would still leave the maternal mortality ratio at 125 in 2030 without corresponding improvements in maternal health services.

Conclusions
Although substantial reductions in maternal mortality between 1970 and 2017 can be attributed to contraceptive use and further contributions to the year 2030 are probable, smaller contributions are likely due to the already relatively high CPR and the challenges that must be overcome to move the CPR significantly higher. The ability of Indonesia to reach the 2030 SDG maternal mortality target of 70 maternal deaths per 100,000 live births will depend primarily upon health system effectiveness in addressing health risks to women once they are pregnant.
PVT1 signals an androgen-dependent transcriptional repression program in prostate cancer cells and a set of the repressed genes predicts high-risk tumors
Authors: Videira Alexandre , Beckedorff Felipe C. , daSilva Lucas F. , Verjovski-Almeida Sergio 
Published: January 2021

AbstractBackgroundAndrogen receptor (AR) and polycomb repressive complex 2 (PRC2) are known to co-occupy the loci of genes that are downregulated by androgen-stimulus. Long intergenic non-coding RNA (lincRNA)PVT1is an overexpressed oncogene that is associated with AR in LNCaP prostate cancer cells, and with PRC2 in HeLa and many other types of cancer cells. The possible involvement ofPVT1in mediating androgen-induced gene expression downregulation in prostate cancer has not been explored.MethodsLNCaP cell line was used. Native RNA-binding-protein immunoprecipitation with anti-AR or anti-EZH2 was followed by RT-qPCR with primers forPVT1. Knockdown ofPVT1with specific GapmeRs (or a control with scrambled GapmeR) was followed by differentially expressed genes (DEGs) determination with Agilent microarrays and with Significance Analysis of Microarrays statistical test. DEGs were tested as a tumor risk classifier with a machine learning Random Forest algorithm run with gene expression data from all TCGA-PRAD (prostate adenocarcinoma) tumors as input. ChIP-qPCR was performed for histone marks at the promoter of one DEG.ResultsWe show thatPVT1knockdown in androgen-stimulated LNCaP cells caused statistically significant expression upregulation/downregulation of hundreds of genes. Interestingly,PVT1knockdown caused upregulation of 160 genes that were repressed by androgen, including a significantly enriched set of tumor suppressor genes, and among themFAS,NOV/CCN3, BMF,HRK, IFIT2, AJUBA, DRAICandTNFRSF21. A 121-gene-set (out of the 160) was able to correctly predict the classification of all 293 intermediate- and high-risk TCGA-PRAD tumors, with a mean ROC area under the curve AUC = 0.89 ± 0.04, pointing to the relevance of these genes in cancer aggressiveness. Native RIP-qPCR in LNCaP showed thatPVT1was associated with EZH2, a component of PRC2.PVT1knockdown followed by ChIP-qPCR showed significant epigenetic remodeling at the enhancer and promoter regions of tumor suppressor geneNOV, one of the androgen-repressed genes that were upregulated uponPVT1silencing.ConclusionsOverall, we provide first evidence thatPVT1was involved in signaling a genome-wide androgen-dependent transcriptional repressive program of tumor suppressor protein-coding genes in prostate cancer cells. Identification of transcriptional inhibition of tumor suppressor genes byPVT1highlights the pathway to the investigation of mechanisms that lie behind the oncogenic role ofPVT1in cancer.
A meta-analysis of the reproducibility of food frequency questionnaires in nutritional epidemiological studies
Authors: Cui Qi , Xia Yang , Wu Qijun , Chang Qing , Niu Kaijun , Zhao Yuhong 
Published: January 2021

Abstract
Background
Reproducibility of FFQs measures the consistency of the same subject at different time points. We performed a meta-analysis to explore the reproducibility of FFQs and factors related to reproducibility of FFQs.

Methods and findings
A systematic literature review was performed before July 2020 using PubMed and Web of Science databases. Pooled intraclass and Spearman correlation coefficients (95% confidence interval) were calculated to assess the reproducibility of FFQs. Subgroup analyses based on characteristics of study populations, FFQs, or study design were performed to investigate factors related to the reproducibility of FFQs. A total of 123 studies comprising 20,542 participants were eligible for the meta-analysis. The pooled crude intraclass correlation coefficients ranged from 0.499 to 0.803 and 0.499 to 0.723 for macronutrients and micronutrients, respectively. Energy-adjusted intraclass correlation coefficients ranged from 0.420 to 0.803 and 0.507 to 0.712 for macronutrients and micronutrients, respectively. The pooled crude and energy-adjusted Spearman correlation coefficients ranged from 0.548 to 0.851 and 0.441 to 0.793, respectively, for macronutrients; and from 0.573 to 0.828 and 0.510 to 0.744, respectively, for micronutrients. FFQs with more food items, 12 months as dietary recall interval (compared to less than 12 months), and a shorter time period between repeated FFQs resulted in superior FFQ reproducibility.

Conclusions
In conclusion, FFQs with correlation coefficients greater than 0.5 for most nutrients may be considered a reliable tool to measure dietary intake. To develop FFQs with higher reproducibility, the number of food items and dietary recall interval should be taken into consideration.