bluuebunny/crossref_metadata_2025 huggingface dataset:
The practice of evaluating epidemic response in humanitarian and low-income settings: a systematic review
Authors: Warsame Abdihamid , Murray Jillian , Gimma Amy , Checchi Francesco
Published: November 2020

Background

Epidemics of infectious disease occur frequently in low-income and humanitarian settings and pose a serious threat to populations. However, relatively little is known about responses to these epidemics. Robust evaluations can generate evidence on response efforts and inform future improvements. This systematic review aimed to (i) identify epidemics reported in low-income and crisis settings, (ii) determine the frequency with which evaluations of responses to these epidemics were conducted, (iii) describe the main typologies of evaluations undertaken and (iv) identify key gaps and strengths of recent evaluation practice.

Methods

Reported epidemics were extracted from the following sources: World Health Organization Disease Outbreak News (WHO DON), UNICEF Cholera platform, Reliefweb, PROMED and Global Incidence Map. A systematic review for evaluation reports was conducted using the MEDLINE, EMBASE, Global Health, Web of Science, WPRIM, Reliefweb, PDQ Evidence and CINAHL Plus databases, complemented by grey literature searches using Google and Google Scholar. Evaluation records were quality-scored and linked to epidemics based on time and place. The time period for the review was 2010–2019.

Results

A total of 429 epidemics were identified, primarily in sub-Saharan Africa, the Middle East and Central Asia. A total of 15,424 potential evaluations records were screened, 699 assessed for eligibility and 132 included for narrative synthesis. Only one tenth of epidemics had a corresponding response evaluation. Overall, there was wide variability in the quality, content as well as in the disease coverage of evaluation reports.

Conclusion

The current state of evaluations of responses to these epidemics reveals large gaps in coverage and quality and bears important implications for health equity and accountability to affected populations. The limited availability of epidemic response evaluations prevents improvements to future public health response. The diversity of emphasis and methods of available evaluations limits comparison across responses and time. In order to improve future response and save lives, there is a pressing need to develop a standardized and practical approach as well as governance arrangements to ensure the systematic conduct of epidemic response evaluations in low-income and crisis settings.
The relationship between body mass index and health-related quality of life in COPD: real-world evidence based on claims and survey data
Authors: Huber Manuel B. , Kurz Christoph , Kirsch Florian , Schwarzkopf Larissa , Schramm Anja , Leidl Reiner
Published: November 2020

Background

Body mass index (BMI) is an important parameter associated with mortality and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD). However, informed guidance on stratified weight recommendations for COPD is still lacking. This study aims to determine the association between BMI and HRQoL across different severity grades of COPD to support patient management.

Methods

We use conjunct analysis of claims and survey data based on a German COPD disease management program from 2016 to 2017. The EQ-5D-5L visual analog scale (VAS) and COPD Assessment Test (CAT) are used to measure generic and disease-specific HRQoL. Generalized additive models with smooth functions are implemented to evaluate the relationship between BMI and HRQoL, stratified by COPD severity.

Results

11,577 patients were included in this study. Mean age was 69.4 years and 59% of patients were male. In GOLD grades 1–3, patients with BMI of around 25 had the best generic and disease-specific HRQoL, whereas in GOLD grade 4, obese patients had the best HRQoL using both instruments when controlled for several variables including smoking status, income, COPD severity, comorbidities, emphysema, corticosteroid use, and days spent in hospital.

Conclusion

This real-world analysis shows the non-linear relationship between BMI and HRQoL in COPD. HRQoL of obese patients with mild to severe COPD might improve following weight reduction. For very severe COPD, a negative association of obesity and HRQoL could not be confirmed. The results hint at the need to stratify COPD patients by disease stage for optimal BMI management.
DARS-AS1 accelerates the proliferation of cervical cancer cells via miR-628-5p/JAG1 axis to activate Notch pathway
Authors: Chen Yihong , Wu Qiumei , Lin Jing , Wei Juanbing
Published: November 2020

Background

Growing evidence has indicated the vital parts of long non-coding RNAs (lncRNAs) in modulating the progression of assorted human cancers, including cervical cancer (CC). Nevertheless, the role and mechanism of aspartyl-tRNA synthetase antisense RNA 1 (DARS-AS1) have been not comprehensively illustrated in CC yet.

Methods

Real-time quantitative polymerase chain reaction (RT-qPCR) was exploited for assessing RNA expression while western blot for protein expression in CC cells. The cell counting kit-8 (CCK-8), colony formation and TdT-mediated dUTP Nick-End Labeling (TUNEL) assays, as well as flow cytometry analysis, were employed to evaluate the modulation of DARS-AS1 on the proliferation and apoptosis of CC cells. In addition, RNA immunoprecipitation (RIP), RNA pull down assay and luciferase reporter assay confirmed the interactivity among DARS-AS1, miR-628-5p and jagged canonical Notch ligand 1 (JAG1). RBP-JK luciferase reporter assay determined the activity of Notch pathway.

Results

DARS-AS1 level was significantly increased in CC cells. Moreover, down-regulation of DARS-AS1 hampered cell the proliferation and accelerated the apoptosis of CC cells. Importantly, DARS-AS1 was a competing endogenous RNA (ceRNA) to elevate JAG1 level through sequestering miR-628-5p, leading to activated Notch pathway to aggravate CC tumorigenesis.

Conclusions

DARS-AS1/miR-628-5p/JAG1/Notch signaling accelerates CC progression, indicating DARS-AS1 as a novel therapeutic target for patients with CC.
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

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

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

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.
Correction to: Dietary patterns of Chinese women of childbearing age during pregnancy and their relationship to the neonatal birth weight
Authors: Yan Hui , Dang Shaonong , Zhang Yaodong , Luo Shuying
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
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

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

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

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

Background

The 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.

Methods

We 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.

Results

The 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.

Conclusions

The 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

Background

Reprogramming 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.

Methods

Human 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.

Results

Chromosomal 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.

Conclusions

Our 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

Background

The 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.

Methods

Molecular 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.

Results

SHOX 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 .

Conclusions

In 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

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.
Longitudinal analysis of healthy colon establishes aspirin as a suppressor of cancer-related epigenetic aging
Authors: Noreen Faiza , Chaber-Ciopinska Anna , Regula Jaroslaw , Schär Primo , Truninger Kaspar
Published: November 2020

Background

Colon cancer (CC) is the third most common cancer worldwide, highlighting the importance of developing effective prevention strategies. Accumulating evidence supports that aspirin use reduces CC incidence. We reported previously that aspirin suppresses age-associated and CC-relevant DNA methylation (DNAm) in healthy colon. Here we addressed the aspirin’s effectiveness in longitudinal cohort.

Methods

We measured genome-wide DNAm in 124 healthy normal mucosa samples taken at baseline (time point 1, t1) and after 10-years follow-up (time point 2, t2) from a longitudinal female screening cohort. We investigated the time-dependent methylation drift in aspirin users and nonusers using multivariable regression and related the modulatory effect of aspirin to colonic epigenome-aging and CC.

Results

Over time, compared to nonusers, long-term (≥ 2 years) aspirin users showed less hypermethylated CpGs (proximal: 17% vs. 87%; distal: 16% vs. 70%) and more hypomethylated CpGs (proximal: 83% vs. 13%; distal: 84% vs. 30%). Overall, users showed 2% (P = 0.02) less mean methylation levels than nonusers in proximal colon and displayed repressed methylation age (mAge). Methylation loss in users occurred at several CC-specific tumor suppressors that gained methylation in nonusers. Methylation loss in users effected genes involved in immune system and inflammation, while methylation gain in nonusers effected genes involved in metabolism.

Conclusions

This is the first longitudinal study demonstrating effectiveness of aspirin-use in suppression of age-related and CC-relevant hypermethylation in the normal colon. These findings provide a rationale for future studies to evaluate loci that may serve as markers to identify individuals that will benefit most from aspirin and hence increase its efficiency in CC prevention and therapy.
miR-214-3p-Sufu-GLI1 is a novel regulatory axis controlling inflammatory smooth muscle cell differentiation from stem cells and neointimal hyperplasia
Authors: He Shiping , Yang Feng , Yang Mei , An Weiwei , Maguire Eithne Margaret , Chen Qishan , Xiao Rui , Wu Wei , Zhang Li , Wang Wen , Xiao Qingzhong
Published: November 2020

Background

Inflammatory smooth muscle cells (iSMCs) generated from adventitial stem/progenitor cells (AdSPCs) have been recognised as a new player in cardiovascular disease, and microRNA-214-3p (miR-214-3p) has been implicated in mature vascular SMC functions and neointimal hyperplasia. Here, we attempted to elucidate the functional involvements of miR-214-3p in iSMC differentiation from AdSPCs and unravel the therapeutic potential of miR-214-3p signalling in AdSPCs for injury-induced neointimal hyperplasia.

Methods

The role of miR-214-3p in iSMC differentiation from AdSPCs was evaluated by multiple biochemistry assays. The target of miR-214-3p was identified through binding site mutation and reporter activity analysis. A murine model of injury-induced arterial remodelling and stem cell transplantation was conducted to study the therapeutic potential of miR-214-3p. RT-qPCR analysis was performed to examine the gene expression in healthy and diseased human arteries.

Results

miR-214-3p prevented iSMC differentiation/generation from AdSPCs by restoring sonic hedgehog-glioma-associated oncogene 1 (Shh-GLI1) signalling. Suppressor of fused (Sufu) was identified as a functional target of miR-214-3p during iSMC generation from AdSPCs. Mechanistic studies revealed that miR-214-3p over-expression or Sufu inhibition can promote nuclear accumulation of GLI1 protein in AdSPCs, and the consensus sequence (GACCACCCA) for GLI1 binding within smooth muscle alpha-actin (SMαA) and serum response factor (SRF) gene promoters is required for their respective regulation by miR-214-3p and Sufu. Additionally, Sufu upregulates multiple inflammatory gene expression (IFNγ, IL-6, MCP-1 and S100A4) in iSMCs. In vivo, transfection of miR-214-3p into the injured vessels resulted in the decreased expression level of Sufu, reduced iSMC generation and inhibited neointimal hyperplasia. Importantly, perivascular transplantation of AdSPCs increased neointimal hyperplasia, whereas transplantation of AdSPCs over-expressing miR-214-3p prevented this. Finally, decreased expression of miR-214-3p but increased expression of Sufu was observed in diseased human arteries.

Conclusions

We present a previously unexplored role for miR-214-3p in iSMC differentiation and neointima iSMC hyperplasia and provide new insights into the therapeutic effects of miR-214-3p in vascular disease.
Deep double-pilot-based hybrid precoding in UAV-enabled mmWave massive MIMO
Authors: Hong Ziyao , Li Ting , Li Fei
Published: November 2020

Unmanned aerial vehicle (UAV)-enabled communication system provides flexibility and reliability compared to conventional ones. Millimeter wave (mmWave) and massive multiple-input–multiple-output (MIMO) have widely been researched since recent years, which are promising techniques for the next and even the later generation communication system. Hybrid precoding, as a method to reduce the high cost in hardware and power brought by massive antenna array, develops fiercely and is often combined to deep learning, a kind of popular optimization tool, which brings an overwhelming performance. On the other hand, there are not so many attentions about the hybrid precoding in time-varying mmWave massive MIMO, which is necessary to be considered in a UAV-enabled communication scenario because the performance will degrade seriously if the channel changed while the transmitter and receiver use the precoding matrix corresponding to the expired channel, yet. In this paper, we propose a double-pilot-based hybrid precoding system, which completes analog precoding and digital precoding separately—predicting the previous one using deep learning structure and updating equivalent channel frequently for the post one by enhancing the frequency of equivalent channel estimation.
Newspaper article-based agent control in smart city simulations
Authors: Kim Euhee , Jang Sejun , Li Shuyu , Sung Yunsick
Published: November 2020

The latest research on smart city technologies mainly focuses on utilizing cities’ resources to improve the quality of the lives of citizens. Diverse kinds of control signals from massive systems and devices such as adaptive traffic light systems in smart cities can be collected and utilized. Unfortunately, it is difficult to collect a massive dataset of control signals as doing so in the real-world requires significant effort and time. This paper proposes a deep generative model which integrates a long short-term memory model with generative adversarial network (LSTM-GAN) to generate agent control signals based on the words extracted from newspaper articles to solve the problem of collecting massive signals. The discriminatory network in the LSTM-GAN takes continuous word embedding vectors as inputs generated by a pre-trained Word2Vec model. The agent control signals of sequential actions are simultaneously predicted by the LSTM-GAN in real time. Specifically, to collect the training data of smart city simulations, the LSTM-GAN is trained based on the Corpus of Contemporary American English (COCA) newspaper dataset, which contains 5,317,731 sentences, for a total of 93,626,203 word tokens, from written texts. To verify the proposed method, agent control signals were generated and validated. In the training of the LSTM-GAN, the accuracy of the discriminator converged to 50%. In addition, the losses of the discriminator and the generator converged from 4527.04 and 4527.94 to 2.97 and 1.87, respectively.
Meta-synthesis of qualitative evidence in road traffic injury prevention: a scoping review of qualitative studies (2000 to 2019)
Authors: Azami-Aghdash Saber
Published: November 2020

Background

A considerable number of qualitative studies have been published in recent years on the issues that the quantitative studies have limitations on. This study aimed at performing a meta-synthesis on qualitative studies on Road Traffic Injuries (RTIs) with a scoping review approach.

Methods

This meta-synthesis study was conducted as a scoping review in 2019. The Arkesy and O’Malley framework was applied which has six steps of identifying the research question, identifying the relevant studies, selecting the studies, charting the data, data analysis and reporting the results, and consultation exercise. The required data were gathered by searching the relevant keywords in databases of PubMed, web of knowledge, Scopus, Cochrane Library, Science Direct, Google scholar, Sid, IranMedex. Extracted data were analyzed by the Content-Analysis method.

Results

Finally, 30 studies were included. Extracted data summarized in five main themes and 17 sub-themes. The main themes were: consequences (individual, family, social, financial), the needs of survivors (social support and healthcare), risk factors (general risk factors, risk factors for motorcyclists, risk factors for children and adolescents), barriers of prevention (general barriers, pre-hospital barriers, emergency, and hospital barriers), and prevention solutions (increasing safety, rules and regulations, education, increasing equipment, scientific solutions) of RTIs.

Conclusion

This study combined the methods of the scoping review and the meta-synthesis to mapping all qualitative studies on the RTIs, with this approach, this study provides extensive and practical information for policy-makers, managers, practitioners, and researchers in the field of RTIs. Also, by applying this approach, the gaps in the existing knowledge and areas in need of further research are identified.
Determination of veterinary pharmaceutical runoffs from a swine manure pile using LC–MS/MS
Authors: Park Min-Kyu , Oh Joo-Yeon , Lee Sung-Eun , Choi Sung-Deuk
Published: November 2020

The mass usage of veterinary pharmaceuticals in farms has contributed to environmental pollution in vicinity waters, soils, and sediments from farms and composting facilities. In the present study, we investigated the usage of four antibiotics (viz., lincomycin, sulfamethazine, sulfamethoxazole, and trimethoprim) to understand their contamination routes from livestock manure piles. Residual levels of these antibiotics in a nearby reservoir were set as a positive control (Site 1), and a swine manure pile in a farm (Site 2) and a soil sample around the manure pile (Site 3) were selected for this study. Artificial rainwater was flowed into the manure sample (Site 2), the soil sample around the manure pile (Site 3), and a soil sample around the vicinity river (Site 4). A stream sample (Site 5) around the manure pile and river water near the manure pile (Site 6) were also collected. For qualitative and quantitative analyses, analytical validation was performed, and all the four antibiotics were detected at Site 1 in the concentration range of 0.03–1.6 µg/L. Lincomycin was the antibiotic with the highest detection level. At Site 2, the detection level of all antibiotics remained at 0.3–17.3 µg/L, and their residual amounts were continuously detected in subsequent samples with approximately 30-fold decrease. The migration of antibiotics was confirmed to be independent of pH value. Therefore, this study indicates that farm manure pile should be thoroughly managed for antibiotic contamination in vicinity areas with periodical monitoring, especially waterways.
Spatiotemporal dynamics, risk areas and social determinants of dengue in Northeastern Brazil, 2014–2017: an ecological study
Authors: do Carmo Rodrigo Feliciano , Silva Júnior José Valter Joaquim , Pastor Andre Filipe , de Souza Carlos Dornels Freire
Published: November 2020

Background

Dengue fever is an arthropod-borne viral disease caused by dengue virus (DENV) and transmitted by Aedes mosquitoes. The Northeast region of Brazil is characterized by having one of the highest dengue rates in the country, in addition to being considered the poorest region. Here, we aimed to identify spatial clusters with the highest dengue risk, as well as to analyze the temporal behavior of the incidence rate and the effects of social determinants on the disease transmission dynamic in Northeastern Brazil.

Methods

This is an ecological study carried out with all confirmed cases of dengue in the Northeast Brazil between 2014 and 2017. Data were extracted from the National Notifiable Diseases Information System (SINAN) and the Brazilian Institute of Geography and Statistics (IBGE). Local empirical Bayesian model, Moran statistics and spatial scan statistics were applied. The association between dengue incidence rate and social determinants was tested using Moran’s bivariate correlation.

Results

A total of 509 261 cases of dengue were confirmed in the Northeast during the study period, 53.41% of them were concentrated in Pernambuco and Ceará states. Spatial analysis showed a heterogeneous distribution of dengue cases in the region, with the highest rates in the east coast. Four risk clusters were observed, involving 815 municipalities (45.45%). Moreover, social indicators related to population density, education, income, housing, and social vulnerability showed a spatial correlation with the dengue incidence rate.

Conclusions

This study provides information on the spatial dynamics of dengue in northeastern Brazil and its relationship with social determinants and can be used in the formulation of public health policies to reduce the impact of the disease in vulnerable populations.
Evolving pituitary hormone deficits in primarily isolated GHD: a review and experts’ consensus
Authors: Binder Gerhard , Schnabel Dirk , Reinehr Thomas , Pfäffle Roland , Dörr Helmuth-Günther , Bettendorf Markus , Hauffa Berthold , Woelfle Joachim
Published: November 2020

Isolated growth hormone deficiency (GHD) is defined by growth failure in combination with retarded bone age, low serum insulin-like growth factor-1, and insufficient GH peaks in two independent GH stimulation tests. Congenital GHD can present at any age and can be associated with significant malformations of the pituitary-hypothalamic region or the midline of the brain. In rare instances, genetic analysis reveals germline mutations of transcription factors involved in embryogenesis of the pituitary gland and the hypothalamus. Acquired GHD is caused by radiation, inflammation, or tumor growth. In contrast to organic GHD, idiopathic forms are more frequent and remain unexplained.

There is a risk of progression from isolated GHD to combined pituitary hormone deficiency (> 5% for the total group), which is clearly increased in children with organic GHD, especially with significant malformation of the pituitary gland. Therefore, it is prudent to exclude additional pituitary hormone deficiencies in the follow-up of children with isolated GHD by clinical and radiological observations and endocrine baseline tests. In contrast to primary disorders of endocrine glands, secondary deficiency is frequently milder in its clinical manifestation. The pituitary hormone deficiencies can develop over time from mild insufficiency to severe deficiency. This review summarizes the current knowledge on diagnostics and therapy of additional pituitary hormone deficits occurring during rhGH treatment in children initially diagnosed with isolated GHD. Although risk factors are known, there are no absolute criteria enabling exclusion of children without any risk of progress to combined pituitary hormone deficiency. Lifelong monitoring of the endocrine function of the pituitary gland is recommended in humans with organic GHD. This paper is the essence of a workshop of pediatric endocrinologists who screened the literature for evidence with respect to evolving pituitary deficits in initially isolated GHD, their diagnosis and treatment.
Transitions in alcohol use over time: a survival analysis
Authors: Koenig Laura B. , Haber Jon Randolph , Jacob Theodore
Published: November 2020

Background

The current study examined the predictors of the onset of alcohol use as well as predictors of remission and relapse, both from heavy drinking and from alcohol dependence. Similarities and differences in both clinical and psychosocial predictors across the transitions were examined.

Methods

A sample of men from the Vietnam Era Twin Registry (N = 1769) completed an assessment of lifetime drinking history, which allowed age markers for starting and stopping different drinking patterns. The men also completed various assessments regarding personality, alcohol motives, and psychiatric diagnoses. Survival analyses were used to examine the predictors of the three transitions of onset, remission, and relapse for the phenotypes of heavy drinking and of alcohol dependence, censoring the individuals who had not yet experienced an event.

Results

As expected, predictors of onset for drinking, heavy drinking, and alcohol dependence were largely consistent and included externalizing symptomology, nicotine dependence, and cotwin history of drinking as risk factors. Predictors of remission from heavy drinking, somewhat similarly to remission from alcohol dependence, included the risk factor of externalizing disorders but also, as predicted, included more risk and protective factors in the psychosocial realm that were not predictors of onset. Contrary to our prediction, relapse to heavy drinking and alcohol dependence were predicted largely by unique psychosocial risk and protective factors including social and coping motives.

Conclusion

Current findings extend the findings of past research to remission and relapse in the later decades of life and have implications for treatment of alcohol use problems.