bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer
Authors: Yu Xiaotang , Zhang Xinchen , Wang Guang , Wang Bo , Ding Yanfang , Zhao Jinyao , Liu Hanlin , Cui Shiying 
Published: November 2020

Abstract

Background
Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by microarray, and miR-206 was one of the most significant miRNAs. The purposes of this study were to evaluate the prognostic and platinum-resistance predictive value of miR-206 in EOC patients and to investigate the functional roles of miR-206 in regulating the platinum resistance of EOC and the underlying mechanism.

Methods
MiRNA expression profiling in EOC specimens was performed using a TaqMan miRNA array. miR-206 expression was confirmed by quantitative real-time PCR (qRT-PCR) analysis. Overexpression of miR-206 in EOC cell lines was achieved by the stable transfection of a recombinant plasmid. In vitro assays of cisplatin cytotoxicity, cell cycle distribution, apoptosis, transwell invasion and cell scratching were employed. Connexin 43 (Cx43) expression was detected by Western blotting. Murine xenograft models were used to determine the effects of miR-206 on platinum resistance in vivo.

Results
miR-206 expression was increased in primary platinum-resistant EOC. High miR-206 expression was related to poor prognosis in EOC patients who received platinum-based chemotherapy and predicted chemoresistance to platinum treatment. Overexpression of miR-206 in cisplatin-sensitive EOC cell lines significantly increased cell viability, migration and invasion in the presence of cisplatin and decreased cisplatin-induced apoptosis. Cx43, a target gene of miR-206, was negatively regulated by miR-206 in EOC cell lines and significantly related to better prognosis in patients who received platinum-based chemotherapy (KmPlot). miR-206 had high expression and Cx43 had low expression in platinum-sensitive EOC cell lines compared with resistant ones. In vivo murine xenograft models showed that miR-206 profoundly promoted the chemoresistance of EOC to cisplatin treatment.

Conclusion
miR-206 was highly expressed in primary platinum-resistant EOCs and functionally promoted platinum resistance in part by downregulating Cx43 expression, thereby providing a useful biomarker for prognostic and platinum-resistance prediction.
Pharmacovigilance of suspected or confirmed therapeutic ineffectiveness of artemisinin-based combination therapy: extent, associated factors, challenges and solutions to reporting
Authors: Kiguba Ronald , Ndagije Helen Byomire , Nambasa Victoria , Manirakiza Leonard , Kirabira Elijah , Serwanga Allan , Olsson Sten , Speybroeck Niko , Mukonzo Jackson 
Published: November 2020

Abstract

Background
Therapeutic ineffectiveness of artemisinin-based combination therapy (ACT) increases the risk of malaria-related morbidity and mortality, and raises healthcare costs. Yet, little has been done to promote the pharmacovigilance (PV) of ACT ineffectiveness in sub-Saharan Africa, particularly in Uganda. This study aimed to determine the extent and associated factors of the past 6 months reporting of suspected or confirmed ACT therapeutic ineffectiveness by healthcare professionals (HCPs), and difficulties and potential solutions to the PV of ACT therapeutic ineffectiveness.

Methods
Survey of 685 HCPs conducted using a self-administered questionnaire from June to July 2018 in a nationally representative sample of public and private health facilities in Uganda. HCPs disclosed if they had spontaneously reported ACT therapeutic ineffectiveness to appropriate authorities in the previous 6 months. Multivariable logistic regression models were used to identify determinants of past 6-months, HCP-reported ACT therapeutic ineffectiveness.

Results
One in five (20%, 137/685; 95% CI 17–23%) HCPs reported ACT therapeutic ineffectiveness to an appropriate authority in the previous 6 months. HCPs commonly reported ACT therapeutic ineffectiveness to immediate supervisors (72%, 106/147), mostly verbally only (80%, 109/137); none had ever submitted a written report of ACT therapeutic ineffectiveness to Uganda’s National Pharmacovigilance Centre. Common difficulties of reporting ACT therapeutic ineffectiveness were: unavailability of reporting procedures (31%, 129/421), poor follow-up of treated patients (22%, 93/421) and absence of reporting tools (16%, 68/421). Factors associated with reporting ACT therapeutic ineffectiveness in the past 6 months were: hospital-status (vs other; OR = 2.4, 95% CI 1.41–4.21), HCPs aged under 25 years (OR = 2.2, 95% CI 1.29–3.76), suspicion of ACT therapeutic ineffectiveness in the past 4 weeks (OR = 2.3, 95% CI 1.29–3.92), receipt of patient-complaint(s) of ACT therapeutic ineffectiveness in the past 4 weeks (OR = 2.9, 95% CI 1.62–5.12) and HCPs from northern (vs central; OR = 0.5, 95% CI 0.28–0.93) and western (vs central; OR = 0.4, 95% CI 0.17–0.77) parts of Uganda.

Conclusion
One in five HCPs reported ACT therapeutic ineffectiveness, mostly verbally to supervisors. The existing adverse drug reaction (ADR)-reporting infrastructure could be leveraged to promote the PV of ACT therapeutic ineffectiveness.
Evaluating the impact of larviciding with Bti and community education and mobilization as supplementary integrated vector management interventions for malaria control in Kenya and Ethiopia
Authors: Mutero Clifford M. , Okoyo Collins , Girma Melaku , Mwangangi Joseph , Kibe Lydia , Ng’ang’a Peter , Kussa Dereje , Diiro Gracious , Affognon Hippolyte , Mbogo Charles M. 
Published: November 2020

Abstract

Background
Malaria prevention in Africa is mainly through the use of long-lasting insecticide treated nets (LLINs). The objective of the study was to assess the effect of supplementing LLINs with either larviciding with Bacillus thuringiensis israelensis (Bti) or community education and mobilization (CEM), or with both interventions in the context of integrated vector management (IVM).

Methods
The study involved a factorial, cluster-randomized, controlled trial conducted in Malindi and Nyabondo sites in Kenya and Tolay site in Ethiopia, to assess the impact of the following four intervention options on mosquitoes and malaria prevalence: LLINs only (arm 1); LLINs and Bti (arm 2); LLINs and CEM (arm 3); and, LLINs combined with Bti and CEM (arm 4). Between January 2013 and December 2015, CDC light traps were used to sample adult mosquitoes during the second, third and fourth quarter of each year in 10 houses in each of 16 villages at each of the three study sites. Larvae were sampled once a fortnight from potential mosquito-breeding habitats using standard plastic dippers. Cross-sectional malaria parasite prevalence surveys were conducted involving a total of 11,846 primary school children during the 3-year period, including 4800 children in Tolay, 3000 in Malindi and 4046 in Nyabondo study sites.

Results
Baseline relative indoor anopheline density was 0.11, 0.05 and 0.02 mosquitoes per house per night in Malindi, Tolay and Nyabondo sites, respectively. Nyabondo had the highest recorded overall average malaria prevalence among school children at 32.4%, followed by Malindi with 5.7% and Tolay 1.7%. There was no significant reduction in adult anopheline density at each of the three sites, which could be attributed to adding of the supplementary interventions to the usage of LLINs. Malaria prevalence was significantly reduced by 50% in Tolay when using LLINs coupled with application of Bti, community education and mobilization. The two other sites did not reveal significant reduction of prevalence as a result of combining LLINs with any of the other supplementary interventions.

Conclusion
Combining LLINs with larviciding with Bti and CEM further reduced malaria infection in a low prevalence setting in Ethiopia, but not at sites with relatively higher prevalence in Kenya. More research is necessary at the selected sites in Kenya to periodically determine the suite of vector control interventions and broader disease management strategies, which when integrated would further reduce adult anopheline populations and malaria prevalence beyond what is achieved with LLINs.
Identifying the determinants of health insurance coverage among Peruvian women of reproductive age: an assessment based on the national Peruvian demographic survey of 2017
Authors: Ramos Rosas Eduardo , Winkler Volker , Brenner Stephan , De Allegri Manuela 
Published: November 2020

Abstract

Background
Like many other Latin America- and Caribbean countries, Peru has introduced a tax-financed health insurance scheme called “Sistema Integral de Salud (SIS)” to foster progress towards Universal Health Coverage. The scheme explicitly targets the poorest sections of the population. Our study explores levels of health insurance coverage and their determinants among Peruvian women following the introduction of SIS. We wish to determine the extent to which the introduction of SIS has effectively closed gaps in insurance coverage and for whom.

Methods
Relying on the 2017 round of ENDES (Encuesta Nacional Demográfica y de Salud Familiar) survey, we analyzed data for 33,168 women aged 15–49. We used multinomial logistic regression to explore the association between health insurance coverage (defined as No Insurance, SIS, Standard Insurance) and women’s socio-demographic and economic characteristics.

Results
Out of the 33,168 women, 25.3% did not have any insurance coverage, 45.5% were covered by SIS and 29.2% were covered by a Standard Insurance scheme. Women in the SIS group were found to have lower educational levels, live in rural areas and more likely to be poorer. Women in the Standard insurance group were found to be more educated, more likely to be “Spanish”, and to be wealthier. Most uninsured women appeared to belong to a middle class, not poor enough to be eligible for SIS, but also not eligible for standard insurance.

Conclusions
Our study confirms that SIS has been effective in increasing coverage among vulnerable women, with coverage rates comparable with those observed among men. Nevertheless, on its own, it has proven to be insufficient to ensure universal coverage among women. Further reforms are needed to ensure that coverage is extended to all population groups.
Association between nontraditional lipid profiles and peripheral arterial disease in Chinese adults with hypertension
Authors: Ding Congcong , Chen Yang , Shi Yumeng , Li Minghui , Hu Lihua , Zhou Wei , Wang Tao , Zhu Lingjuan , Huang Xiao , Bao Huihui , Cheng Xiaoshu 
Published: November 2020

Abstract

Background
Data on the relationship between nontraditional lipid profiles [total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio, non-high-density lipoprotein cholesterol (non-HDL-C)] and the risk of peripheral artery disease (PAD) are limited. The present study investigated the relationship of nontraditional lipid indices with PAD in hypertensive patients.

Methods
This cross-sectional study was performed among 10,900 adults with hypertension. Participants were diagnosed with PAD when their ankle-brachial index (ABI) was < 0.9. The association between nontraditional lipid profiles and PAD was examined using multivariate logistic regression analysis and the restricted cubic spline.

Results
All nontraditional lipid indices were independently and positively associated with PAD in a dose-response fashion. After multivariable adjustment, the per SD increments of the TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C were all significantly associated with 37, 14, 40, and 24% higher risk for PAD, respectively. The adjusted ORs (95% CI) for PAD were 1.77 (1.31, 2.40), 1.71 (1.25, 2.34), 2.03 (1.50, 2.74), and 1.70 (1.25, 2.31) when comparing the highest tertile to the lowest tertile of the TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C, respectively.

Conclusions
Among Chinese hypertensive adults, all nontraditional lipid indices were positively associated with PAD, and the LDL-C/HDL-C and TC/HDL-C ratios were better than the other nontraditional lipid indices for predicting PAD. These findings may improve the risk stratification of cardiovascular disease and dyslipidemia management.

Trial registration
CHiCTR, ChiCTR1800017274. Registered 20 July 2018.
Predictors of survival after surgery with curative intent for perihilar cholangiocarcinoma
Authors: Geers Joachim , Jaekers Joris , Topal Halit , Aerts Raymond , Vandoren Cindy , Vanden Boer Guy , Topal Baki 
Published: November 2020

Abstract

Background
Several clinicopathological predictors of survival after curative surgery for perihilar cholangiocarcinoma (pCCA) have been identified; however, conflicting reports remain. The aim was to analyse clinical and oncological outcomes after curative resection of pCCA and to determine prognostic factors.

Methods
Eighty-eight consecutive patients with pCCA underwent surgery with curative intent between 1998 and 2017. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Twenty-one prognostic factors were evaluated using multivariate Cox regression models.

Results
Postoperative complications were observed in 73 (83%) patients of which 41 (47%) were severe complications (therapy-oriented severity grading system (TOSGS) grade > 2), including a 90-day mortality of 9% (n = 8). Overall survival (OS) and disease-free survival (DFS) rates at 5 and 10 years after surgery were 33% and 19%, and 37% and 30%, respectively. Independent predictors of OS were locoregional lymph node metastasis (LNM) (risk ratio (RR) 2.12, confidence interval (CI) 1.19–3.81, p = 0.011), patient American Society of Anesthesiologists (ASA) physical status classification system > 2 (RR 2.10, CI 1.03–4.26, p = 0.043), and depth of tumour penetration (pT) > 2 (RR 2.58, CI 1.03–6.30, p = 0.043). The presence of locoregional LNM (RR 2.95, CI 1.51–5.90, p = 0.002) and caudate lobe resection (RR 2.19, CI 1.01–5.14, p = 0.048) were found as independent predictors of DFS.

Conclusions
Curative surgery for pCCA carries high risks with poor long-term survival. Locoregional LNM was the only predictor for both OS and DFS.
Operationalising health systems thinking: a pathway to high effective coverage
Authors: Vaz Lara M. E. , Franco Lynne , Guenther Tanya , Simmons Kelsey , Herrera Samantha , Wall Stephen N. 
Published: November 2020

AbstractBackgroundThe global health community has recognised the importance of defining and measuring the effective coverage of health interventions and their implementation strength to monitor progress towards global mortality and morbidity targets. Existing health system models and frameworks guide thinking around these measurement areas; however, they fall short of adequately capturing the dynamic and multi-level relationships between different components of the health system. These relationships must be articulated for measurement and managed to effectively deliver health interventions of sufficient quality to achieve health impacts. Save the Children’s Saving Newborn Lives programme and EnCompass LLC, its evaluation partner, developed and applied the Pathway to High Effective Coverage as a health systems thinking framework (hereafter referred to as the Pathway) in its strategic planning, monitoring and evaluation.MethodsWe used an iterative approach to develop, test and refine thinking around the Pathway. The initial framework was developed based on existing literature, then shared and vetted during consultations with global health thought leaders in maternal and newborn health.ResultsThe Pathway is a robust health systems thinking framework that unpacks system, policy and point of intervention delivery factors, thus encouraging specific actions to address gaps in implementation and facilitate the achievement of high effective coverage. The Pathway includes six main components – (1) national readiness; (2) system structures; (3) management capacity; (4) implementation strength; (5) effective coverage; and (6) impact. Each component is comprised of specific elements reflecting the range of facility-, community- and home-based interventions. We describe applications of the Pathway and results for in-country strategic planning, monitoring of progress and implementation strength, and evaluation.ConclusionsThe Pathway provides a cohesive health systems thinking framework that facilitates assessment and coordinated action to achieve high coverage and impact. Experiences of its application show its utility in guiding strategic planning and in more comprehensive and effective monitoring and evaluation as well as its potential adaptability for use in other health areas and sectors.
Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells
Authors: Liu Xinyu , Li Conghui , Zheng Kang , Zhao Xiaofeng , Xu Xiaofeng , Yang Aifen , Yi Min , Tao Huaping , Xie Binghua , Qiu Mengsheng , Yang Junlin 
Published: November 2020

AbstractBackgroundReprogramming somatic cells to induced pluripotent stem cells (iPSCs) has opened new therapeutic possibilities. However, karyotypic abnormalities detected in iPSCs compromised their utility, especially chromosomal aberrations found at early passages raised serious safety concerns. The mechanism underlying the chromosomal abnormality in early-passage iPSCs is not known.MethodsHuman dermal fibroblasts (HDFs) were stimulated with KMOS (KLF4, cMYC, OCT4 and SOX2) proteins to enhance their proliferative capacity and many vigorous clones were obtained. Clonal reprogramming was carried out by KMOS mRNAs transfection to confirm the ‘chromosomal mutagenicity’ of reprogramming process. Subculturing was performed to examine karyotypic stability of iPSCs after the re-establishment of stemness. And antioxidant N-acetyl-cysteine (NAC) was added to the culture medium for further confirmming the mutagenicity in the first few days of reprogramming.ResultsChromosomal aberrations were found in a small percentage of newly induced iPS clones by reprogramming transcription factors. Clonal reprogramming ruled out the aberrant chromosomes inherited from rare karyotypically abnormal parental cell subpopulation. More importantly, the antioxidant NAC effectively reduced the occurrence of chromosomal aberrations at the early stage of reprogramming. Once iPS cell lines were established, they restored karyotypic stability in subsequent subculturing.ConclusionsOur results provided the first line of evidence for the ‘chromosomal mutagenicity’ of reprogramming process.
SHOX deficiency in children with growth impairment: evaluation of known and new auxological and radiological indicators
Authors: Vannelli Silvia , Baffico Maria , Buganza Raffaele , Verna Francesca , Vinci Giulia , Tessaris Daniele , Di Rosa Gianpaolo , Borraccino Alberto , de Sanctis Luisa 
Published: November 2020

AbstractBackgroundThe phenotypic features of SHOX deficiency (SHOX-D) are highly variable and can be very mild, especially in young children. The aim of this retrospective study was to evaluate auxological and radiological indicators that could be predictive of SHOX-D in children.MethodsMolecular analysis of the SHOX gene was performed in 296 subjects with growth impairment or skeletal disproportion, without alternative diagnosis. Auxological variables and radiographs of the hand, wrist and forearm were evaluated.ResultsSHOX mutations (88% inherited, 12% de novo) were identified in 52 subjects. The most predictive auxological indicators of SHOX-D were an increased sitting height/height ratio and a decreased arm span/height ratio. The convexity of distal radial metaphysis at X-ray, not yet reported in literature, was also found to be predictive of SHOX-D. In young children, stratification of data by bone age also highlighted ulnar tilt, lucency of the ulnar border of the distal radius and enlarged radius as the radiological signs most related to SHOX-D .ConclusionsIn this study, the analysis of auxological and radiological indicators in SHOX-D children allowed to identify an additional early radiological sign and underlines the importance of family auxological evaluation.
Cis-acting lnc-eRNA SEELA directly binds histone H4 to promote histone recognition and leukemia progression
Authors: Fang Ke , Huang Wei , Sun Yu-Meng , Chen Tian-Qi , Zeng Zhan-Cheng , Yang Qian-Qian , Pan Qi , Han Cai , Sun Lin-Yu , Luo Xue-Qun , Wang Wen-Tao , Chen Yue-Qin 
Published: November 2020

Abstract

Background
Long noncoding enhancer RNAs (lnc-eRNAs) are a subset of stable eRNAs identified from annotated lncRNAs. They might act as enhancer activity-related therapeutic targets in cancer. However, the underlying mechanism of epigenetic activation and their function in cancer initiation and progression remain largely unknown.

Results
We identify a set of lncRNAs as lnc-eRNAs according to the epigenetic signatures of enhancers. We show that these lnc-eRNAs are broadly activated in MLL-rearranged leukemia (MLL leukemia), an aggressive leukemia caused by a chromosomal translocation, through a mechanism by which the HOXA cluster initiates enhancer activity, and the epigenetic reader BRD4 cooperates with the coregulator MLL fusion oncoprotein to induce transcriptional activation. To demonstrate the functional roles of lnc-eRNAs, two newly identified lnc-eRNAs transcribed from the SEELA eRNA cluster (SEELA), SEELA1 and SEELA2, are chosen for further studies. The results show that SEELA mediated cis-activated transcription of the nearby oncogene Serine incorporate 2 (SERINC2) by directly binding to the K31 amino acid (aa) of histone H4. Chromatin-bound SEELA strengthens the interaction between chromatin and histone modifiers to promote histone recognition and oncogene transcription. Further studies show that the SEELA-SERINC2 axis regulated aspects of cancer metabolism, such as sphingolipid synthesis, to affect leukemia progression.

Conclusions
This study shows that lnc-eRNAs are epigenetically activated by cancer-initiating oncoproteins and uncovers a cis-activating mechanism of oncogene transcription control based on lnc-eRNA-mediated epigenetic regulation of enhancer activity, providing insights into the critical roles of lnc-eRNAs in cancer initiation and progression.