bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of an e-health readiness assessment framework for developing countries
Authors: Mauco Kabelo Leonard , Scott Richard E. , Mars Maurice 
Published: June 2020

Abstract
Background
Studies document e-health as having potential to improve quality of healthcare services, resulting in both developed and developing countries demonstrating continued interest in e-health uptake and use. e-Health implementations are not always successful as high failure rates have been reported in both developed and developing countries. These failures are often a result of lack of e-health readiness. e-Health readiness has been defined as the preparedness of healthcare institutions or communities for the anticipated change brought by programs related to information and communication technologies. As such it is critical to conduct an e-health readiness assessment prior to implementation of e-health innovations so as to reduce chances of project failure. Noting the absence of an adequate e-health readiness assessment framework (eHRAF) suitable for use in developing countries, the authors conceptualised, designed, and created a developing country specific eHRAF to aid in e-health policy planning. The aim of this study was to validate the developed eHRAF and to determine if it required further refinement before empirical testing.

Methods
Published options for a framework validation process were adopted, and fifteen globally located e-health experts engaged. Botswana experts were engaged using saturation sampling, while international experts were purposively selected. Responses were collated in an Excel spreadsheet, and NVivo 11 software used to aid thematic analysis of the open ended questions.

Results
Analysis of responses showed overall support for the content and format of the proposed eHRAF. Equivocal responses to some open ended questions were recorded, most of which suggested modifications to terms within the framework. One expert from the developed world had alternate views.

Conclusions
The proposed eHRAF provides guidance for e-health policy development and planning by identifying, in an evidence based manner, the major areas to be considered when preparing for an e-health readiness assessment in the context of developing countries.
Programmatic options for monitoring malaria in elimination settings: easy access group surveys to investigate Plasmodium falciparum epidemiology in two regions with differing endemicity in Haiti
Authors: Druetz Thomas , Stresman Gillian , Ashton Ruth A. , van den Hoogen Lotus L. , Joseph Vena , Fayette Carl , Monestime Frank , Hamre Karen E. , Chang Michelle A. , Lemoine Jean F. , Drakeley Chris , Eisele Thomas P. 
Published: June 2020

Abstract
Background
As in most eliminating countries, malaria transmission is highly focal in Haiti. More granular information, including identifying asymptomatic infections, is needed to inform programmatic efforts, monitor intervention effectiveness, and identify remaining foci. Easy access group (EAG) surveys can supplement routine surveillance with more granular information on malaria in a programmatically tractable way. This study assessed how and which type of venue for EAG surveys can improve understanding malaria epidemiology in two regions with different transmission profiles.

Methods
EAG surveys were conducted within the departments of Artibonite and Grand’Anse (Haiti), in regions with different levels of transmission intensity. Surveys were conducted in three venue types: primary schools, health facilities, and churches. The sampling approach varied accordingly. Individuals present at the venues at the time of the survey were eligible whether they presented malaria symptoms or not. The participants completed a questionnaire and were tested for Plasmodium falciparum by a highly sensitive rapid diagnostic test (hsRDT). Factors associated with hsRDT positivity were assessed by negative binomial random-effects regression models.

Results
Overall, 11,029 individuals were sampled across 39 venues in Artibonite and 41 in Grand’Anse. The targeted sample size per venue type (2100 in Artibonite and 2500 in Grand’Anse) was reached except for the churches in Artibonite, where some attendees left the venue before they could be approached or enrolled. Refusal rate and drop-out rate were < 1%. In total, 50/6003 (0.8%) and 355/5026 (7.1%) sampled individuals were hsRDT positive in Artibonite and Grand’Anse, respectively. Over half of all infections in both regions were identified at health facilities. Being male and having a current or reported fever in the previous 2 weeks were consistently identified with increased odds of being hsRDT positive.

Conclusions
Surveys in churches were problematic because of logistical and recruitment issues. However, EAG surveys in health facilities and primary schools provided granular information about malaria burden within two departments in Haiti. The EAG surveys were able to identify residual foci of transmission that were missed by recent national surveys. Non-care seeking and/or asymptomatic malaria infections can be identified in this alternative surveillance tool, facilitating data-driven decision-making for improved targeting of interventions.
Association between the non-HDL-cholesterol-to-HDL-cholesterol ratio and the risk of gallbladder polyp formation among men: a retrospective cohort study
Authors: Zhao Xiaofang , Zheng Huabo , Shan Shengshuai , Wang Kun , Zhang Meng , Xie Songpu , Liu Chengyun 
Published: June 2020

Abstract
Background
Dyslipidaemia and male sex are associated with gallbladder polyp (GBP) formation. However, the potential relation between the non-high-density lipoprotein-cholesterol-to-high-density lipoprotein-cholesterol (non-HDL-c/HDL-c) ratio and GBPs in men is unclear.

Methods
A total of 1866 eligible subjects were selected for this retrospective cohort study from Wuhan Union Hospital between April 1, 2013, and November 30, 2014. Clinical and laboratory data of subjects were collected. Patients with GBPs or cholecystectomy at baseline, with missing data for baseline lipid profiles, following abdominal ultrasonography or taking lipid-lowering drugs were excluded. The patients were divided into five groups based on their non-HDL-c/HDL-c ratios, and descriptive analyses of the baseline data were performed. A Cox proportional hazards model was applied to estimate the relationship between the non-HDL-c/HDL-c ratio and GBPs.

Results
After a median follow-up of 1 year, 7.34% (n = 137) of the subjects developed GBPs. Compared with subjects without GBPs, those who developed GBPs after follow-up had significantly higher triglyceride (TG) levels and non-HDL-c/HDL-c ratios. The prevalence of GBPs showed a linearity increment with age, peaked in the 30–39 years group, 40–49 years group and 50–59 years group, and then declined slightly. The results of univariate analysis showed that the non-HDL-c/HDL-c ratio (hazard ratio (HR) = 1.29, 95% confidence interval (CI), 1.05–1.60, P = 0.0159) was positively correlated with GBPs. In the fully adjusted Cox regression model, the HRs were 2.24 for quintile 2 (95% CI: 1.13–4.44, P = 0.0203), 1.50 for quintile 3 (95% CI: 0.73–3.10, P = 0.269), 2.52 for quintile 4 (95% CI: 1.26–5.01, P = 0.0087) and 2.13 for quintile 5 (95% CI: 1.04–4.37, P = 0.0397). No interaction was found among the subgroups.

Conclusions
A higher non-HDL-c/HDL-c ratio is independently related to a higher risk of GBP formation in Chinese men. Further research is needed to investigate whether this association exists in different regions and races.
Mediating effects of lipids on the association between smoking and coronary artery disease risk among Chinese
Authors: Song Wenjing , Guan Jieqiong , He Pan , Fan Siyu , Zhi Hong , Wang Lina 
Published: June 2020

AbstractObjectiveThe mechanism between smoking and coronary artery disease (CAD) remains unclear. It is likely that lipid (including triglycerides (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C)) have been functioning as one of the mediators between smoking and the CAD occurrence. The study aimed to investigate the mediating effect of lipid on the relationship between smoking and CAD risk.MethodsThe case-control study included 2048 subjects. General linear regression analysis was used to corroborate the association between smoking and lipid levels. Univariate and multivariate logistic regression analysis were performed to reveal the relationship between smoking, lipid and the risk of CAD. Mediation analysis was used to investigate whether the association between smoking and CAD risk was mediated by lipid.ResultsSmoking was found to be associated with the risk of CAD (odds ratio (OR) = 1.34, 95% confidence interval (CI): 1.05–1.71,P = 0.019). Regression analysis showed that TG, TC and HDL-C were associated with CAD (OR = 2.69, 95%CI: 2.12–3.40,P < 0.001; OR = 0.34, 95%CI: 0.29–0.43,P < 0.001; OR = 0.37, 95%CI: 0.30–0.47,P < 0.001). Moreover, the ratio of TG to HDL-C (TG/HDL-C) was also related to CAD (OR = 4.45, 95%CI: 3.52–5.64,P < 0.001). Mediation analysis showed that among the effects of smoking on CAD, 17.52% was mediated by lipid, in which HDL-C accounted for 11.16% and TG accounted for 6.36%. Further analysis showed that the effect was also partially mediated by TG/HDL-C, which was accounted for 28%.ConclusionsLipid plays a partial mediation on the association between smoking and CAD risk. The study provides a clue on the mediation effect of lipids on the relationship between smoking and CAD risks, which is a novel insight to the progression of CAD.
Integrated analysis reveals critical glycolytic regulators in hepatocellular carcinoma
Authors: Lu Chenying , Fang Shiji , Weng Qiaoyou , Lv Xiuling , Meng Miaomiao , Zhu Jinyu , Zheng Liyun , Hu Yumin , Gao Yang , Wu Xulu , Mao Jianting , Tang Bufu , Zhao Zhongwei , Huang Li , Ji Jiansong 
Published: June 2020

Abstract
Background
Cancer cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect. Increased aerobic glycolysis supports cancer cell survival and rapid proliferation and predicts a poor prognosis in cancer patients.

Methods
Molecular profiles from The Cancer Genome Atlas (TCGA) cohort were used to analyze the prognostic value of glycolysis gene signature in human cancers. Gain- and loss-of-function studies were performed to key drivers implicated in hepatocellular carcinoma (HCC) glycolysis. The molecular mechanisms underlying Osteopontin (OPN)-mediated glycolysis were investigated by real-time qPCR, western blotting, immunohistochemistry, luciferase reporter assay, and xenograft and diethyl-nitrosamine (DEN)-induced HCC mouse models.

Results
Increased glycolysis predicts adverse clinical outcome in many types of human cancers, especially HCC. Then, we identified a handful of differentially expressed genes related to HCC glycolysis. Gain- and loss-of-function studies showed that OPN promotes, while SPP2, LECT2, SLC10A1, CYP3A4, HSD17B13, and IYD inhibit HCC cell glycolysis as revealed by glucose utilization, lactate production, and extracellular acidification ratio. These glycolysis-related genes exhibited significant tumor-promoting or tumor suppressive effect on HCC cells and these effects were glycolysis-dependent. Mechanistically, OPN enhanced HCC glycolysis by activating the αvβ3-NF-κB signaling. Genetic or pharmacological blockade of OPN-αvβ3 axis suppressed HCC glycolysis in xenograft tumor model and hepatocarcinogenesis induced by DEN.

Conclusions
Our findings reveal crucial determinants for controlling the Warburg metabolism in HCC cells and provide a new insight into the oncogenic roles of OPN in HCC.
ALICE: a randomized placebo-controlled phase II study evaluating atezolizumab combined with immunogenic chemotherapy in patients with metastatic triple-negative breast cancer
Authors: Kyte J. A. , Røssevold A. , Falk R. S. , Naume B. 
Published: June 2020

Abstract
Background
Immunotherapy with checkpoint inhibitors (CI) represents an important novel development in cancer treatment. Metastatic triple-negative breast cancer (mTNBC) is incurable, with a median survival of only ~ 13 months. We have initiated the randomized placebo-controlled phase IIb study ALICE, evaluating PD-L1 blockade combined with immunogenic chemotherapy in mTNBC patients (n = 75). Intriguingly, the host immune response is strongly predictive for the effect of chemotherapy in mTNBC. In the ALICE trial, we release the brake on the immune response by use of atezolizumab, an inhibitory antibody against PD-L1. We utilize anthracyclines, shown to trigger the immune system, and low-dose cyclophosphamide, which has been reported to counter immunosuppressive cells.

Methods
ALICE is a randomized, double-blind, placebo-controlled exploratory phase II study evaluating the safety and efficacy of atezolizumab when combined with immunogenic chemotherapy in subjects with mTNBC. The trial will enroll 75 evaluable subjects, randomized 2:3 into two arms (A:B). The patients receive identical chemotherapy, i.e. pegylated liposomal doxorubicin (PLD 20 mg/m2 intravenously every 2nd week) + cyclophosphamide (50 mg per day, first 2 weeks in each 4 week cycle). Patients in arm A receive placebo, while patients in arm B receive atezolizumab. The primary objectives are assessment of toxicity and progression-free survival. The secondary objectives include overall survival, tumor response rate, clinical benefit rate, patient reported outcomes, biomarkers and assessment of tumor-immune evolution during therapy.

Discussion
The question of how CI should be combined with chemotherapy, is a key challenge facing the field. There is a strong preclinical rationale for exploring if anthracyclines, which are considered to induce immunogenic cell death, synergize with PD-L1 blockade, and if low-dose cyclophosphamide counters tumor tolerance. However, the data from patients is as yet very limited, and the clinical evaluation of these hypotheses is among the key objectives in the ALICE trial. The study includes extensive biobanking and translational sub-projects, also addressing other clinically important questions. These analyses may uncover mechanisms of drug efficacy or tumor resistance, and identify biomarkers allowing personalized therapy. If the trial suggests acceptable safety of the ALICE therapy and provide a signal of clinical efficacy, further studies are warranted.
Trial registration NCT03164993, May 24th 2017; https://clinicaltrials.gov/ct2/show/record/NCT03164993
ENG-releasing subdermal implants in postpartum teenagers – an open-label trial study protocol
Authors: Barbieri M. M. , Juliato C. R. T. , Bahamondes L. , Surita F. G. 
Published: June 2020

Abstract
Background
Higher than expected adolescent pregnancy high rates continue globally, with repeated unplanned pregnancy (UP) in this age group is a public health problem. In Brazil, 16% of pregnancies occur in adolescents under 18 years old, with high maternal morbidity and mortality rates in this age group. Effective and safe contraception is required to reduce UP rates. The objective of our study is to evaluate acceptance of etonogestrel (ENG)-releasing subdermal contraceptive implant after childbirth, before discharge, as well as clinical performance up to one year after placement. Comparison between teenagers who opt for ENG-implant versus other contraceptive methods after childbirth will be also evaluated, specifically regarding UP, continuation and discontinuation rates and reasons, body composition, pelvic ultrasound characteristics and user satisfaction.

Methods
A non-randomized open-label trial will be conducted with teenagers after childbirth and followed up to one year at the Women’s Hospital, University of Campinas (UNICAMP), Campinas, Brazil. The study group will consist of patients who accepted to use ENG-implant and placed before discharge. The comparison group will include adolescents who choose to use other contraceptive methods at the first postpartum visit (42 ± 3 days after childbirth). All women will follow-up at 40–60 days postpartum, as well as, at 6 and 12 months post-enrollment. Patient satisfaction, contraceptive effectiveness, reasons of discontinuation, continuation rate and body composition will be evaluated. Transvaginal ultrasound and electric bio impedance tests will be performed at all follow-up appointments. A 5% significance level was assumed, as well as, a sampling error (absolute) for 10% prevalence. The sample size was calculated at n = 100, obtaining an estimate of 50 to 70 adolescents who would accept the method offered, according to the prevalence and sample error assumed.

Discussion
Long-acting reversible contraceptive (LARC) methods include subdermal implants and intrauterine contraceptives, are considered first line contraception for teenagers. Immediate postpartum use is a safe option, which significantly reduces rates of repeated UP and all the undesirable consequences inherent to this process.

Trial registration
This study was approved by the Ethics and Research Commission of UNICAMP (CAAE: 92869018.5.0000.5404) and the Brazilian Registry of Clinical Trials (REBEC): http://www.ensaiosclinicos.gov.br/rg/RBR-4z7bc6, (number 2.901.752).
A ligation and restriction enzyme independent cloning technique: an alternative to conventional methods for cloning hard-to-clone gene segments in the influenza reverse genetics system
Authors: Bhat Sushant , Bialy Dagmara , Sealy Joshua E. , Sadeyen Jean-Remy , Chang Pengxiang , Iqbal Munir 
Published: June 2020

Abstract
Background
Reverse genetics is used in many laboratories around the world and enables the creation of tailor-made influenza viruses with a desired genotype or phenotype. However, the process is not flawless, and difficulties remain during cloning of influenza gene segments into reverse genetics vectors (pHW2000, pHH21, pCAGGS). Reverse genetics begins with making cDNA copies of influenza gene segments and cloning them into bi-directional (pHW2000) or uni-directional plasmids (pHH21, pCAGGS) followed by transfection of the recombinant plasmid(s) to HEK-293 T or any other suitable cells which are permissive to transfection. However, the presence of internal restriction sites in the gene segments of many field isolates of avian influenza viruses makes the cloning process difficult, if employing conventional methods. Further, the genetic instability of influenza gene-containing plasmids in bacteria (especially Polymerase Basic 2 and Polymerase Basic 1 genes; PB2 and PB1) also leads to erroneous incorporation of bacterial genomic sequences into the influenza gene of interest.

Methods
Herein, we report an easy and efficient ligation and restriction enzyme independent (LREI) cloning method for cloning influenza gene segments into pHW2000 vector. The method involves amplification of megaprimers followed by PCR amplification of megaprimers using a bait plasmid, DpnI digestion and transformation.

Results
Hard-to-clone genes: PB2 of A/chicken/Bangladesh/23527/2014 (H9N2) and PB1 of A/chicken/Bangladesh/23527/2014 (H9N2), A/chicken/Jiangxi/02.05YGYXG023-P/2015 (H5N6) and A/Chicken/Vietnam/H7F-14-BN4–315/2014 (H9N2) were cloned into pHW2000 using our LREI method and recombinant viruses were subsequently rescued.

Conclusion
The LREI cloning procedure represents an alternative strategy for cloning influenza gene segments which have internal restriction sites for the enzymes used in reverse genetics. Further, the problem of genetic instability in bacteria can be alleviated by growing recombinant bacterial cultures at a lower temperature. This technique can be applied to clone any influenza gene segment using universal primers, which would help in rapid generation of influenza viruses and facilitate influenza research and vaccine development.
The platform GrowScreen-Agar enables identification of phenotypic diversity in root and shoot growth traits of agar grown plants
Authors: Nagel Kerstin A. , Lenz Henning , Kastenholz Bernd , Gilmer Frank , Averesch Andreas , Putz Alexander , Heinz Kathrin , Fischbach Andreas , Scharr Hanno , Fiorani Fabio , Walter Achim , Schurr Ulrich 
Published: June 2020

AbstractBackgroundRoot system architecture and especially its plasticity in acclimation to variable environments play a crucial role in the ability of plants to explore and acquire efficiently soil resources and ensure plant productivity. Non-destructive measurement methods are indispensable to quantify dynamic growth traits. For closing the phenotyping gap, we have developed an automated phenotyping platform,GrowScreen-Agar, for non-destructive characterization of root and shoot traits of plants grown in transparent agar medium.ResultsThe phenotyping system is capable to phenotype root systems and correlate them to whole plant development of up to 280Arabidopsisplants within 15 min. The potential of the platform has been demonstrated by quantifying phenotypic differences within 78Arabidopsisaccessions from the 1001 genomes project. The chosen concept ‘plant-to-sensor’ is based on transporting plants to the imaging position, which allows for flexible experimental size and design. As transporting causes mechanical vibrations of plants, we have validated that daily imaging, and consequently, moving plants has negligible influence on plant development. Plants are cultivated in square Petri dishes modified to allow the shoot to grow in the ambient air while the roots grow inside the Petri dish filled with agar. Because it is common practice in the scientific community to growArabidopsisplants completely enclosed in Petri dishes, we compared development of plants that had the shoot inside with that of plants that had the shoot outside the plate. Roots of plants grown completely inside the Petri dish grew 58% slower, produced a 1.8 times higher lateral root density and showed an etiolated shoot whereas plants whose shoot grew outside the plate formed a rosette. In addition, the setup with the shoot growing outside the plate offers the unique option to accurately measure both, leaf and root traits, non-destructively, and treat roots and shoots separately.ConclusionsBecause theGrowScreen-Agarsystem can be moved from one growth chamber to another, plants can be phenotyped under a wide range of environmental conditions including future climate scenarios. In combination with a measurement throughput enabling phenotyping a large set of mutants or accessions, the platform will contribute to the identification of key genes.
Recent trends in stem cell therapy for premature ovarian insufficiency and its therapeutic potential: a review
Authors: Na Jeeyoon , Kim Gi Jin 
Published: June 2020

AbstractStem cell therapy is attracting attention in the field of regenerative medicine and is advancing rapidly. Many recent studies have applied stem cell therapy to treat reproductive system diseases; however, data are not yet available as to whether this therapy shows enhanced therapeutic effects. This paper analyzes recent preclinical studies on stem cell therapy for ovarian dysfunction in several types of animal models. Several clinical trials and pending projects are also discussed. This review will provide a background for developing stem cell therapies to enhance ovarian function.