bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of a multi-step heterologous pathway in Saccharomyces cerevisiae for the production of abscisic acid
Authors: Otto Maximilian , Teixeira Paulo Gonçalves , Vizcaino Maria Isabel , David Florian , Siewers Verena 
Published: December 2019

AbstractBackgroundThe sesquiterpenoid abscisic acid (ABA) is mostly known for regulating developmental processes and abiotic stress responses in higher plants. Recent studies show that ABA also exhibits a variety of pharmacological activities. Affordable and sustainable production will be required to utilize the compound in agriculture and as a potential pharmaceutical.Saccharomyces cerevisiaeis an established workhorse for the biotechnological production of chemicals. In this study, we constructed and characterised an ABA-producingS. cerevisiaestrain using the ABA biosynthetic pathway fromBotrytis cinerea.ResultsExpression of theB. cinereagenesbcaba1,bcaba2,bcaba3andbcaba4was sufficient to establish ABA production in the heterologous host. We characterised the ABA-producing strain further by monitoring ABA production over time and, since the pathway contains two cytochrome P450 enzymes, by investigating the effects of overexpressing the nativeS. cerevisiaeor theB. cinereacytochrome P450 reductase. Both, overexpression of the native or heterologous cytochrome P450 reductase, led to increased ABA titres. We were able to show that ABA production was not affected by precursor or NADPH supply, which suggested that the heterologous enzymes were limiting the flux towards the product. TheB. cinereacytochrome P450 monooxygenases BcABA1 and BcABA2 were identified as pathway bottlenecks and balancing the expression levels of the pathway enzymes resulted in 4.1-fold increased ABA titres while reducing by-product formation.ConclusionThis work represents the first step towards a heterologous ABA cell factory for the commercially relevant sesquiterpenoid.
RETRACTED ARTICLE: Correlations between chromobox homolog 8 and key factors of epithelial–mesenchymal transition in hepatocellular carcinoma
Authors: Zhu Xiaonian , Luo Wei , Bei Chunhua , Kong Juan , Zhang Shidong , Fu Yuanyuan , Li Di , Tan Shengkui 
Published: December 2019

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, especially in China, with high metastasis and poor prognosis. Recently, as the core component of the polycomb repressive complexes 1 (PRC1), chromobox protein homolog 8 (CBX8) is considered as an oncogene and prognostic marker in HCC.

Methods
A tissue microarray of 166 paired HCC and adjacent non-tumor samples were collected to identify the relationship between CBX8 and epithelial mesenchymal transition (EMT) associated proteins by Spearman correlation analysis. Knock-down of CBX8 in HCC cells was conducted to detect the biologic functions of CBX8 in HCC metastasis.

Results
We found out that CBX8 was over-expressed in HCC and its expression was closely related to the metastasis of HCC patients. In addition, knock-down of CBX8 was found to inhibit the invasion and migration ability of HCC cells. Moreover, there was a significant relationship between expression of CBX8 and EMT associated proteins both in HCC cells and tumor tissues.

Conclusions
Our results indicate that CBX8 promotes metastasis of HCC by inducing EMT process.
Extended spectrum β-lactamase producing uropathogenic Escherichia coli and the correlation of biofilm with antibiotics resistance in Nepal
Authors: Shrestha Raju , Khanal Santosh , Poudel Pramod , Khadayat Karan , Ghaju Sajani , Bhandari Anita , Lekhak Sunil , Pant Narayan Dutt , Sharma Manisha , Marasini Bishnu P. 
Published: December 2019

Abstract
Background
Urinary tract infection (UTI) is one of the frequently diagnosed infectious diseases which is caused mainly by Escherichia coli. E. coli confers resistance against the two major classes of antibiotics due to the production of extended spectrum β-lactamase enzymes (ESBL), biofilm, etc. Biofilm produced by uropathogenic E. coli (UPEC) protects from host immune system and prevent entry of antimicrobial compounds. The main objective of this cross-sectional study was to determine the correlation of biofilm production and antibiotic resistance as well as to characterize the pgaA and pgaC genes responsible for biofilm formation among uropathogenic ESBL producing E. coli.

Methods
A total of 1977 mid-stream urine samples were examined and cultured for bacterial strain identification. ESBL was detected by combined disc method following CLSI whereas biofilm formation was analyzed by semi-quantitative method. Furthermore, the pgaA and pgaC genes responsible for biofilm formation in UPEC were detected by multiplex PCR. All the statistical analyses were done via IBM SPSS Statistics 21 where Pearson’s correlation test were used to determine correlation (−1 ≥ r ≤ 1).

Results
E. coli was the predominant causative agent, which accounted 159 (59.3%) of the Gram-negative bacteria, where 81 (50.9%) E. coli strains were found to be ESBL producers. In addition, 86 (54.1%) E. coli strains were found to be biofilm producers. Both the pgaA and pgaC genes were detected in 45 (93.7%) the UPEC isolates, which were both biofilm and ESBL producers. Moreover, there was a positive correlation between biofilm and ESBL production.

Conclusion
The analyses presented weak positive correlation between biofilm and ESBL production in which biofilm producing UPEC harbors both pgaA and pgaC genes responsible for biofilm formation.
Chemotherapeutic drugs stimulate the release and recycling of extracellular vesicles to assist cancer cells in developing an urgent chemoresistance
Authors: Wang Xiaokun , Qiao Dongjuan , Chen Likun , Xu Meng , Chen Shupeng , Huang Liyan , Wang Fang , Chen Zhen , Cai Jiye , Fu Liwu 
Published: December 2019

AbstractBackgroundChemotherapy is a widely used treatment for cancer. However, the development of acquired multidrug resistance (MDR) is a serious issue. Emerging evidence has shown that the extracellular vesicles (EVs) mediate MDR, but the underlying mechanism remains unclear, especially the effects of chemotherapeutic agents on this process.MethodsExtracellular vesicles isolation was performed by differential centrifugation. The recipient cells that acquired ATP-binding cassette sub-family B member 1 (ABCB1) proteins were sorted out from co-cultures according to a stringent multi-parameter gating strategy by fluorescence-activated cell sorting (FACS). The transfer rate of ABCB1 was measured by flow cytometry. The xenograft tumor models in mice were established to evaluate the transfer of ABCB1 in vivo. Gene expression was detected by real-time PCR and Western blotting.ResultsHerein, we show that a transient exposure to chemotherapeutic agents can strikingly increase Rab8B-mediated release of extracellular vesicles (EVs) containing ABCB1 from drug-resistant cells, and accelerate these EVs to circulate back onto plasma membrane of sensitive tumor cells via the down-regulation of Rab5. Therefore, intercellular ABCB1 transfer is significantly enhanced; sensitive recipient cells acquire a rapid but unsustainable resistance to evade the cytotoxicity of chemotherapeutic agents. More fascinatingly, in the xenograft tumor models, chemotherapeutical drugs also locally or distantly increase the transfer of ABCB1 molecules. Furthermore, some Non-small-cell lung carcinoma (NSCLC) patients who are undergoing primary chemotherapy have a rapid increase of ABCB1 protein in their monocytes, and this is obviously associated with poor chemotherapeutic efficacy.ConclusionsChemotherapeutic agents stimulate the secretion and recycling of ABCB1-enriched EVs through the dysregulation of Rab8B and Rab5, leading to a significant increase of ABCB1 intercellular transfer, thus assisting sensitive cancer cells to develop an urgent resistant phenotype. Our findings provide a new molecular mechanism of how chemotherapeutic drugs assist sensitive cancer cells in acquiring an urgent resistance.
Novel nanomedicine with a chemical-exchange saturation transfer effect for breast cancer treatment in vivo
Authors: Jia Yanlong , Wang Chaochao , Zheng Jiehua , Lin Guisen , Ni Dalong , Shen Zhiwei , Huang Baoxuan , Li Yan , Guan Jitian , Hong Weida , Chen Yuanfeng , Wu Renhua 
Published: December 2019

AbstractBackgroundNanomedicine is a promising new approach to cancer treatment that avoids the disadvantages of traditional chemotherapy and improves therapeutic indices. However, the lack of a real-time visualization imaging technology to monitor drug distribution greatly limits its clinical application. Image-tracked drug delivery is of great clinical interest; it is useful for identifying those patients for whom the therapy is more likely to be beneficial. This paper discusses a novel nanomedicine that displays features of nanoparticles and facilitates functional magnetic resonance imaging but is challenging to prepare.ResultsTo achieve this goal, we synthesized an acylamino-containing amphiphilic block copolymer (polyethylene glycol-polyacrylamide-polyacetonitrile, PEG-b-P(AM-co-AN)) by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PEG-b-P(AM-co-AN) has chemical exchange saturation transfer (CEST) effects, which enable the use of CEST imaging for monitoring nanocarrier accumulation and providing molecular information of pathological tissues. Based on PEG-b-P(AM-co-AN), a new nanomedicine PEG-PAM-PAN@DOX was constructed by nano-precipitation. The self-assembling nature of PEG-PAM-PAN@DOX made the synthesis effective, straightforward, and biocompatible. In vitro studies demonstrate decreased cytotoxicity of PEG-PAM-PAN@DOX compared to free doxorubicin (half-maximal inhibitory concentration (IC50), mean ~ 0.62 μg/mL vs. ~ 5 μg/mL), and the nanomedicine more efficiently entered the cytoplasm and nucleus of cancer cells to kill them. Further, in vivo animal experiments showed that the nanomedicine developed was not only effective against breast cancer, but also displayed an excellent sensitive CEST effect for monitoring drug accumulation (at about 0.5 ppm) in tumor areas. The CEST signal of post-injection 2 h was significantly higher than that of pre-injection (2.17 ± 0.88% vs. 0. 09 ± 0.75%,p < 0.01).ConclusionsThe nanomedicine with CEST imaging reflects the characterization of tumors and therapeutic functions has great potential medical applications.
HIV/HCV co-infection and associated risk factors among injecting drug users in Dar es Salaam, Tanzania: potential for HCV elimination
Authors: Leyna Germana Henry , Makyao Neema , Mwijage Alexander , Ramadhan Angela , Likindikoki Samuel , Mizinduko Mucho , Leshabari Melkizedeck Thomas , Moen Kåre , Mmbaga Elia John 
Published: December 2019

Abstract
Background
Chronic HCV infection causes substantial morbidity and mortality and, in co-infection with HIV, may result in immunological and virological failure following antiretroviral treatment. Estimates of HCV infection, co-infection with HIV and associated risk practices among PWID are scarce in Africa. This study therefore aimed at estimating the prevalence of HCV and associated risk factors among PWID in the largest metropolitan city in Tanzania to inform WHO elimination recommendations.

Methods
An integrated bio-behavioral survey using respondent-driven sampling was used to recruit PWID residing in Dar es Salaam, Tanzania. Following face-to-face interviews, blood samples were collected for HIV and HCV testing. Weighted modified Poisson regression modeling with robust standard errors was used in the analysis.

Results
A total of 611 PWID with a median age of 34 years (IQR, 29–38) were recruited through 4 to 8 waves. The majority of participants (94.3%) were males, and the median age at first injection was 24 years (IQR, 19–30). Only 6.55% (40/611) of participants reported to have been enrolled in opioid treatment programs. The weighted HCV antibody prevalence was 16.2% (95%CI, 13.0–20.1). The corresponding prevalence of HIV infection was 8.7% (95%CI, 6.4–11.8). Of the 51 PWID who were infected with HIV, 22 (43.1%) were HCV seropositive. Lack of access to clean needles (adjusted prevalence ratio (APR), 1.76; 95%CI, 1.44; 12.74), sharing a needle the past month (APR, 1.72; 95%CI, 1.02; 3.00), not cleaning the needle the last time shared (APR, 2.29; 95%CI, 1.00; 6.37), and having unprotected not using a transactional sex (APR, 1.87; 95%CI, 1.00; 3.61) were associated with increased risk of HCV infection. On the other hand, not being on opioid substitution therapy was associated with 60% lower likelihood of infection.

Conclusions
The HCV antibody prevalence among PWID is lower than global estimates indicating potential for elimination. Improving access to safe injecting paraphernalia, promoting safer injecting practices is the focus of prevention programing. Screening for HIV/HCV co-infection should be intensified in HIV care, opioid substitution programs, and other point of care for PWID. Use of direct-acting antiretroviral treatment would accelerate the achievement of hepatitis infection elimination goal by 2030.
Doctor retention and distribution in post-apartheid South Africa: tracking medical graduates (2007–2011) from one university
Authors: George Ann , Blaauw Duane , Thompson Jarred , Green-Thompson Lionel 
Published: December 2019

Abstract
Background
Doctor emigration from low- and middle-income countries represents a financial loss and threatens the equitable delivery of healthcare. In response to government imperatives to produce more health professionals to meet the country’s needs, South African medical schools increased their student intake and changed their selection criteria, but little is known about the impact of these changes. This paper reports on the retention and distribution of doctors who graduated from the University of the Witwatersrand, South Africa (SA), between 2007 and 2011.

Methods
Data on 988 graduates were accessed from university databases. A cross-sectional descriptive email survey was used to gather information about graduates’ demographics, work histories, and current work settings. Frequency and proportion counts and multiple logistic regressions of predictors of working in a rural area were conducted. Open-ended data were analysed using content analysis.

Results
The survey response rate was 51.8%. Foreign nationals were excluded from the analysis because of restrictions on them working in SA. Of 497 South African respondents, 60% had completed their vocational training in underserved areas. At the time of the study, 89% (444) worked as doctors in SA, 6.8% (34) practised medicine outside the country, and 3.8% (19) no longer practised medicine. Eighty percent of the 444 doctors still in SA worked in the public sector. Only 33 respondents (6.6%) worked in rural areas, of which 20 (60.6%) were Black. Almost half (47.7%) of the 497 doctors still in SA were in specialist training appointments.

Conclusions
Most of the graduates were still in the country, with an overwhelmingly urban and public sector bias to their distribution. Most doctors in the public sector were still in specialist training at the time of the study and may move to the private sector or leave the country. Black graduates, who were preferentially selected in this graduate cohort, constituted the majority of the doctors practising in rural areas. The study confirms the importance of selecting students with rural backgrounds to provide doctors for underserved areas. The study provides a baseline for future tracking studies to inform the training of doctors for underserved areas.
Developing evidence briefs for policy: a qualitative case study comparing the process of using a guidance-contextualization workbook in Peru and Uganda
Authors: Alvarez Elizabeth , Lavis John N. , Brouwers Melissa , Carmona Clavijo Gloria , Sewankambo Nelson , Solari Lely , Schwartz Lisa 
Published: December 2019

AbstractBackgroundTranslating research evidence from global guidance into policy can help strengthen health systems. A workbook was developed to support the contextualization of the WHO’s ‘Optimizing health worker roles to improve maternal and newborn health’ (OptimizeMNH) guidance. This study evaluated the use of the workbook for the development of evidence briefs in two countries — Peru and Uganda. Findings surrounding contextual factors, steps in the process and evaluation of the workbook are presented.MethodsA qualitative embedded case study was used. The case was the process of using the workbook to support the contextualization of global health systems guidance, with local evidence, to develop evidence briefs. Criterion sampling was used to select the countries, participants for interviews and documents included in the study. A template-organizing style and constant comparison were used for data analysis.ResultsA total of 19 participant-observation sessions and 8 interviews were conducted, and 50 documents were reviewed. Contextual factors, including the cadres, or groups, of health workers available in each country, the way the problem and its causes were framed, potential policy options to address the problem, and implementation considerations for these policy options, varied substantially between Peru and Uganda. However, many similarities were found in the process of using the workbook. Overall, the workbook was viewed positively and participants in both countries would use it again for other topics.ConclusionsOrganizations that produce global guidance, such as WHO, need to consider institutionalizing the application of the workbook into their guidance development processes to help users at the national/subnational level create actionable and context-relevant policies. Feedback mechanisms also need to be established so that the evidence briefs and health policies arising from global guidance are tracked and the findings coming out of such guideline contextualization processes can be taken into consideration during future guidance development and research priority-setting.
The impact of National Health Insurance upon accessibility of health services and financial protection from catastrophic health expenditure: a case study of Savannakhet province, the Lao People’s Democratic Republic
Authors: Bodhisane Somdeth , Pongpanich Sathirakorn 
Published: December 2019

Abstract
Introduction
Many schemes have been implemented by the government of the Lao People’s Democratic Republic to provide equity in health service utilisation. Initially, health service utilisations were fully supported by the government and were subsequently followed by the Revolving Drug Fund. In the 2000s, four health financing schemes, namely the Social Security Organization, the State Authority for Social Security, the Health Equity Fund and Community-Based Health Insurance (CBHI), were introduced with various target groups. However, as these voluntary schemes have suffered from a very low enrolment rate, the government decided to pilot the National Health Insurance (NHI) scheme, which offers a flat, co-payment system for health service utilisation. This study aims to assess the effectiveness of the NHI in terms of its accessibility and in providing financial protection from catastrophic health expenditure.

Methods
The data collection process was implemented in hospitals of two districts of Savannakhet province. A structured questionnaire was used to retrieve all required information from 342 households; the information comprised of the socioeconomics of the household, accessibility to health services and financial payment for both outpatient and inpatient department services. Binary logistic regression models were used to discover the impact of NHI in terms of accessibility and financial protection. The impact of NHI was then compared with the outcomes of the preceding, voluntary CBHI scheme, which had been the subject of earlier studies.

Results
Under the NHI, it was found that married respondents, large households and the level of income significantly increased the probability of accessibility to health service utilisation. Most importantly, NHI significantly improved accessibility for the poorest income quantile. In terms of financial protection, households with an existing chronic condition had a significantly higher chance of suffering financial catastrophe when compared to households with healthy members. As probability of catastrophic expenditure was not affected by income level, it was indicated that NHI is able to provide equity in financial protection.

Conclusion
The models found that the NHI significantly enhances accessibility for poor income households, improving health service distribution and accessibility for the various income levels when compared to the CBHI coverage. Additionally, it was also found that NHI had enhanced financial protection since its introduction. However, the NHI policy requires a dramatically high level of government subsidy; therefore, there its long-term sustainability remains to be determined.
Palliative Care Evidence Review Service (PaCERS): a knowledge transfer partnership
Authors: Mann Mala , Woodward Amanda , Nelson Annmarie , Byrne Anthony 
Published: December 2019

AbstractThe importance of linking evidence into practice and policy is recognised as a key pillar of a prudent approach to healthcare; it is of importance to healthcare professionals and decision-makers across the world in every speciality. However, rapid access to evidence to support service redesign, or to change practice at pace, is challenging. This is particularly so in smaller specialties such as Palliative Care, where pressured multidisciplinary clinicians lack time and skill sets to locate and appraise the literature relevant to a particular area. Therefore, we have initiated the Palliative Care Evidence Review Service (PaCERS), a knowledge transfer partnership through which we have developed a clear methodology to conduct evidence reviews to support professionals and other decision-makers working in palliative care.PaCERS methodology utilises modified systematic review methods as there is no agreed definition or an accepted methodology for conducting rapid reviews. This paper describes the stages involved based on our iterative recent experiences and engagement with stakeholders, who are the potential beneficiaries of the research. Uniquely, we emphasise the process and opportunities of engagement with the clinical workforce and policy-makers throughout the review, from developing and refining the review question at the start through to the importance of demonstrating impact. We are faced with the challenge of the trade-off between the timely transfer of evidence against the risk of impacting on rigour. To address this issue, we try to ensure transparency throughout the review process. Our methodology aligns with key principles of knowledge synthesis in defining a process that is transparent, robust and improving the efficiency and timeliness of the review.Our reviews are clinically or policy driven and, although we use modified systematic review methods, one of the key differences between published review processes and our review process is in our relationship with the requester. This streamlining approach to synthesising evidence in a timely manner helps to inform decisions faced by clinicians and decision-makers in healthcare settings, supporting, at pace, knowledge transfer and mobilisation.