bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis
Authors: Qin Kang , Hou Helei , Liang Yu , Zhang Xiaochun 
Published: April 2020

AbstractBackground The prognostic significance of TP53 concurrent mutations in patients with epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)- mutated advanced non–small-cell lung cancer (NSCLC) who received EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs based targeted therapy remains controversial. Therefore, the present meta-analysis was performed to investigate the association between TP53 concurrent mutations and prognosis of patients with advanced NSCLC undergoing EGFR-TKIs or ALK-TKIs treatments. Methods Eligible studies were identified by searching the online databases PubMed, Embase, Medline, The Cochrane library and Web of Science. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to clarify the correlation between TP53 mutation status and prognosis of patients. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results In total, 15 studies with 1342 patients were included for final analysis. Overall, concurrent TP53 mutation was associated with unfavorable progression-free survival (PFS) (HR=1.88, 95%CI: 1.59-2.23, p<0.001, I2=0.0%, P=0.792) and overall survival (OS) (HR=1.92, 95%CI: 1.55-2.38, p<0.001, I2=0.0%, P=0.515). Subgroup analysis based on type of targeted therapy (EGFR-TKIs or ALK-TKIs, pathological type of cancer (adenocarcinoma only or all NSCLC subtypes) and line of treatment (first-line only or all lines) all showed that TP53 mutations was associated with shorter survivals of patients with EGFR-TKIs or ALK-TKIs treatments. Particularly, in patients with first-line EGFR-TKIs treatment, significantly poorer prognosis was observed in patients with TP53 concurrent mutations (pooled HR for PFS: 1.69, 95% CI 1.25-2.27, P<0.001, I2=0.0%, P=0.473; pooled HR for OS: 1.94, 95% CI 1.36-2.76, P<0.001, I2=0.0%, P=0.484). Begg’s funnel plots and Egger’s tests indicated no significant publication bias in this study. Conclusions This meta-analysis indicated that concurrent TP53 mutations was a negative prognostic factor and associated with poorer outcomes of patients with EGFR-TKIs or ALK-TKIs treatments in advanced NSCLC. In addition, our study provided evidence that TP53 mutations might be involved in primary resistance to EGFR-TKIs treatments in patients with sensitive EGFR mutations in advanced NSCLC.
Institutional Delivery Service Utilization and Associated Factors in Ethiopia: A Systematic Review and Meta Analysis
Authors: Nigusie Adane , Azale Telake , Yitayal Mezgebu 
Published: April 2020

Abstract
Background: Different primary studies in Ethiopia showed the weight of institutional delivery service utilization and the factors associated with it. However, variation among those studies was seen. This study was aimed to estimate the pooled national prevalence and associated factors of Institutional delivery service utilization in Ethiopia.Methods: PubMed, Cochrane library, Web of Science, and Google Scholar were searched. A funnel plot and Egger’s regression test were used to see publication bias. I-squared statistic was applied to check heterogeneity of studies. A weighted Dersimonian laired random effect model was applied to estimate the pooled national prevalence and the effect size of associated factors.Result: A total of twenty four studies were included in this review. The pooled prevalence of Institutional delivery service utilization was 31% (95% CI: 0.30, 0.31; I2 = 0.00%). Attitude towards institutional delivery of 3 studies(AOR=2.83; 95% CI 1.35,5.92 ), maternal age at first pregnancy of 4 studies((AOR= 3.59; 95% CI 2.27,5.69 )), residence setting of 7 studies (AOR= 3.84; 95% CI 1.31, 11.25), educational status of 5 studies(AOR=2.91;95% 1.88,4.52), availability of information source of 6 studies(AOR= 1.80;95% CI 1.16,2.78), ANC follow-up of 13 studies((AOR= 2.57 95% CI 1.46,4.54 )), frequency of ANC follow up of 4 studies(AOR= 4.04;95% CI 1.21,13.46), knowledge of institutional delivery & danger signs during pregnancy of 11 studies((AOR=3.04;95% CI 1.76 ,5.24 )) and place of birth the most recent birth of 4 studies(AOR=8.44;95% CI 5.75,12.39) were identified factors of institutional delivery service utilization.Conclusions: The findings of this review found several modifiable factors such as empowering women through education, promoting antenatal care to prevent home delivery, increasing awareness of women through mass media and making services more accessible would likely to increase utilization of institutional delivery.
Access to health care for people with disabilities in rural Malawi: what are the barriers?
Authors: Harrison Josephine , Thomson Rachael , Banda Hastings T. , Mbera Grace B. , Gregorius Stefanie , Stenberg Berthe , Marshall Tim 
Published: April 2020

Abstract
Background

People with disabilities experience significant health inequalities. In Malawi, where most individuals live in low-income rural settings, many of these inequalities are exacerbated by restricted access to health care services. This qualitative study explores the barriers to health care access experienced by individuals with a mobility or sensory impairment, or both, living in rural villages in Dowa district, central Malawi. In addition, the impact of a chronic lung condition, alongside a mobility or sensory impairment, on health care accessibility is explored.

Methods

Using data from survey responses obtained through the Research for Equity And Community Health (REACH) Trust’s randomised control trial in Malawi, 12 adult participants, with scores of either 3 or 4 in the Washington Group Short Set (WGSS) questions, were recruited. The WGSS questions concern a person’s ability in core functional domains (including seeing, hearing and moving), and a score of 3 indicates ‘a lot of difficulty’ whilst 4 means ‘cannot do at all’. People with cognitive impairments were not included in this study. All who were selected for the study participated in an individual in-depth interview and full recordings of these were then transcribed and translated.

Results

Through thematic analysis of the transcripts, three main barriers to timely and adequate health care were identified: 1) Cost of transport, drugs and services, 2) Insufficient health care resources, and 3) Dependence on others. Attitudinal factors were explored and, whilst unfavourable health seeking behaviour was found to act as an access barrier for some participants, community and health care workers’ attitudes towards disability were not reported to influence health care accessibility in this study.

Conclusions

This study finds that health care access for people with disabilities in rural Malawi is hindered by closely interconnected financial, practical and social barriers. There is a clear requirement for policy makers to consider the challenges identified here, and in similar studies, and to address them through improved social security systems and health system infrastructure, including outreach services, in a drive for equitable health care access and provision.

Key words

Health care access, barriers, disability, impairment, Malawi, rural, in-depth interviews
Changes in health inequalities for patients with diabetes among middle-aged and elderly in China from 2011 to 2015
Authors: Cao Guizhen , Cui Zhizhen , Ma Qinghua , Wang Congju , Xu Yong , Sun Hongpeng , Ma Yana 
Published: April 2020

Abstract
Objective: The purpose of this paper is to measure income-related health inequality among middle-aged and elderly patients with diabetes in China from 2011 to 2015 and to investigate factors that might be related to this inequality. Methods: The data for this study were obtained from the China Health and Retirement Longitudinal Study that was carried out in 2011, 2013 and 2015. In total, 48519 Chinese middle-aged and elderly patients were included (15457 in 2011, 16576 in 2013 and 16486 in 2015 ). A principal component analysis was performed to measure asset-based economic status. The concentration index was used to measure income-related inequality in patients with diabetes. Additionally, we decomposed the concentration index to identify factors that explained wealth-related inequality in patients with diabetes. Results: The prevalence of self-reported diabetes among middle-aged and elderly Chinese adults was 5.61%, 7.49% and 8.99% in 2011, 2013 and 2015, respectively. The concentration indices and 95% confidence intervals for diabetes were 0.1359 (0.0525-0.0597), 0.1207 (0.0709-0.0789), 0.1021 (0.0855-0.0942) in 2011, 2013, and 2015, respectively , which are indicative of inequality that favors the rich. The decomposition of the concentration index showed that urban location (39.38%), BMI (31.16%), education level (7.28%), and region (6.09%) had positive contributions to the measured inequality in diabetes in China in 2015. Age (-29.93%) had a negative contribution to inequality. Conclusions: The findings confirm a health inequality in diabetes that favor the rich. Furthermore, the inequality declined from 2011 to 2015. We suggest that policy and intervention strategies should be developed to alleviate this health inequality, such as establishing an integrated urban-rural medical insurance scheme.
First description of antimicrobial resistance in carbapenem-susceptible Klebsiella pneumoniae after imipenem treatment, driven by outer membrane remodeling
Authors: Tian Xuebin , Wang Qiongdan , New Laura Perlaza-Jiménez , Zheng Xiangkuo , Zhao Yajie , New Vijay Dhanasekaran , Fang Renchi , Li Jiahui , Wang Chong , Liu Haiyang , New Trevor Lithgow , Cao Jianming , Zhou Tieli 
Published: April 2020

Abstract
Background:The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a looming threat to human health. Although there are numerous studies regarding porin alteration in association with the production of ESBLs and/or AmpC β-lactamase, a systematic study on the treatment-emergence of porins alteration in antibiotic resistance does not yet exist. The aim of this study was to investigate the underlying mechanism and evolution of resistance of K. pneumoniae during carbapenem treatment.
Results:Here, we report three strains (FK-2624, FK-2723 and FK-2820) isolated from one patient before and after imipenem treatment during hospitalization. Antibiotic susceptibility testing indicated that that the first isolate, FK-2624, was susceptible to almost all tested antimicrobials, being resistant only to fosfomycin. The subsequent isolates FK-2723 and FK-2820 were multidrug resistant (MDR). After imipenem therapy, FK-2820 had evolved to be carbapenem-resistant. PCR and Genome Sequencing analysis indicated that oqxA, and fosA5, were identified in all three strains. In addition, FK-2624 also harbored bla SHV-187 and blaTEM-116. The blaSHV-187 and blaTEM-116 genes were not detected in FK-2723 and FK-2820. blaDHA-1, qnrB4, aac (6’)-IIc, and blaSHV-12, EreA2, CatA2, SulI, and tetD , were identified in both FK-2723 and FK-2820. Moreover, the genes bla DHA -1, qnrB4, aac(6’)-IIc were co-harbored on a plasmid. Of the virulence factors found in this study, ybtA, ICEKp6, mrkD, entB, iroN, rmpA2-6, wzi16 and capsular serotype K57 were found in the three isolates. The results of pairwise comparisons, multi-locus sequencing typing (MLST) and pulsed-field gel electrophoresis (PFGE) revealed high homology among the isolates. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results showed that isolate FK-2820 lacked OmpK36, with genome sequence data validating that there was a premature stop codon in the ompK36 gene and real-time RT-PCR suggesting high turnover of the ompK36 non-sense transcript in FK-2820, with the steady-state mRNA level 0.007 relative to the initial isolate.
Conclusion:This study in China highlight that the alteration of outer membrane porins due to the 14-day use of imipenem play a potential role in leading to clinical presentation of carbapenem-resistance. This is the first description of increased resistance developing from a carbapenem-susceptible K. pneumoniae with imipenem treatment driven by outer membrane remodeling.
Why is tobacco control progress in Indonesia stalled? - A qualitative analysis of interviews with tobacco control experts
Authors: Astuti Putu Ayu Swandewi , Assunta Mary , Freeman Becky 
Published: April 2020

AbstractBackground Indonesia shoulders a significant tobacco burden, with almost two million cases of tobacco-related illnesses and more than two hundred thousand tobacco-related deaths annually. Indonesian tobacco control is progressing but lags behind other countries. Our study evaluates factors that contribute to the slow progress of tobacco policy change in Indonesia from the perspective of tobacco control experts (TCEs). Method We conducted qualitative interviews with four international and ten national TCEs, who have been active in tobacco control for at least 5 years. Our interview guideline included questions on the current tobacco control situation in Indonesia and explored reasons why tobacco control is progressing so slowly. The interviews were conducted either in English or Bahasa Indonesia, recorded and then transcribed verbatim. We conducted a thematic analysis based on five core causal factors for policy adoption: institutions, networks, socio-economic factors, agendas and ideas. Results The multistage delay of tobacco policy adoption is principally due to political structures and policy hierarchy, complex bureaucracy, unclear roles and responsibilities, and a high degree of corruption. The low bargaining position and lack of respect for the Ministry of Health also contributes. There are contrasting frames of tobacco as a strategic economic asset and tobacco control as a sovereignty threat. There is an imbalance of power and influence between well entrenched and resourced tobacco industry networks compared to relatively young and less established tobacco control networks. The policy agenda is likely influenced by the privileged position of tobacco in Indonesia as a socially acceptable product with high consumption. There are constraints on transferring ideas and evidence to successful policy adoption. Conclusion Tobacco companies have substantially influenced both policy decisions and public perceptions, signifying a power imbalance within the government system and broader networks. Acceding to and enforcing the World Health Organization-Framework Convention on Tobacco Control (WHO-FCTC) would enable the Indonesian government to shift the power imbalance towards public health stakeholders. Tobacco control advocates must enhance their network cohesion and embrace other community groups to improve engagement and communication with policymakers.
Earthquake Preparedness of Households and Its Predictors Based on Health Belief Model
Authors: Rostami-Moez Masoumeh , Rabiee-Yeganeh Mohammad , Shokouhi Mohammadreza , Dosti-Irani Amin , Rezapur-Shahkolai Forouzan 
Published: April 2020

Abstract
Background : Earthquakes are one of the most destructive natural disasters in which many people are injured, disabled, or died. Although Iran has only one percent of the world's population, its earthquake-related deaths are six percent. Therefore, this study aimed to determine the level of earthquake preparedness of households and its predictors using the Health Belief Model (HBM) . Methods : This observational descriptive and analytical study was conducted on 933 households in Hamadan province, located in the west of Iran, in 2019. Multistage random cluster sampling was used for selecting the participants. The inclusion criteria were being at least 18 years old and being able to answer the questions. A questionnaire was used for data collection including earthquake preparedness, awareness of earthquake response, predictors of earthquake preparedness based on the HBM, and demographic information. Analysis of variance, independent t-test, and a linear regression model was used . Results : The mean age of participants was approximately 38.29 ±12.80 years. Furthermore, 60.83% of the participants did not complete a post-secondary education. The earthquake preparedness was low (approximately 30%) among households. There was a significant relationship between earthquake preparedness and gender, homeownership, marriage status, and previous earthquake experience (P <0.001). Regarding the HBM constructs, perceived benefits, cues to action, and self-efficacy were significant predictors of earthquake preparedness (P <0.01). conclusions: Earthquake preparedness was insufficient. Besides, perceived benefits, cues to action, and self-efficacy were predictors of earthquake preparedness. It is suggested that health providers take into account these predictors for designing future interventions. Keywords : Crises, Hazards, Health promotion, Health education, Natural disasters, Safety
Hypoxic hepatocellular carcinoma cells acquire arsenic trioxide resistance through upregulating HIF-1α expression
Authors: Chen Yaoting , Li Huiqing , Chen Dong , Jiang Xiongying , Wang Weidong , Li Dan , Shan Hong 
Published: April 2020

Abstract
Background : Although arsenic trioxide (ATO) is used in the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials, it is not satisfactory in terms of improving HCC patients’ overall survival. Intratumoral hypoxia and overexpression of hypoxia-inducible-1α (HIF-1α) may result in ATO-resistance and tumor progression. We investigated the mechanisms involving HIF-1α expression and acquired ATO chemoresistance in HCC cells and mice. Methods: The therapeutic effects of ATO in normoxic and hypoxic HCC cells were assessed using cell viability and apoptosis assays in vitro and a xenograft model in vivo . mRNA and protein expression of HIF-1α, P-glycoprotein, and VEGF were measured by qRT-PCR and western blotting. HIF-1α inhibition was performed to investigate the mechanism of ATO-resistance. VEGF secretion was tested using ELISA and tube-formation assays. Results : Compared to normoxic cells, hypoxic HCC cells were more resistant to ATO, with higher IC 50 values and less apoptosis, and upregulated HIF-1α protein expression, accompanied with the enhancement of P-glycoprotein and VEGF synthesis after ATO treatment. VEGF secretion was elevated in the supernatant of ATO-treated HCC cells, and this change can potentiate angiogenesis in vitro . HIF-1α inhibition attenuated ATO-resistance and angiogenesis, and promoted the anticancer effects of ATO both in vitro and in vivo by downregulating therapy-induced P-glycoprotein and VEGF overexpression. Conclusions : Hypoxic HCC cells acquire ATO resistance by upregulating HIF-1α levels; thus, combining ATO with a HIF-1α-targeting agent may lead to enhanced antitumor effects in HCC.
Drug resistance occurred in a newly characterized preclinical model of lung cancer brain metastasis.
Authors: Shah Neal , Liu Zhongwei , Tallman Rachel M. , Mohammad Afroz , Sprowls Samuel A , Saralkar Pushkar A. , Vickers Schuyler D. , Pinti Mark V. , Gao Weimin , Lockman Paul R 
Published: April 2020

Abstract
Background
Cancer metastasis and drug resistance have traditionally been studied separately, though these two lethal pathological phenomena almost always occur concurrently. Brain metastasis occurs in a large proportion of lung cancer patients (~30%). Once diagnosed, patients have a poor prognosis surviving typically less than 1 year due to lack of treatment efficacy.

Methods
Human metastatic lung cancer cells (PC-9-Br) were injected into the left cardiac ventricle of female athymic nude mice. Brain lesions were allowed to grow for 21 days, animals were then randomized into treatment groups and treated until presentation of neurological symptoms or when moribund. Prior to tissue collection mice were injected with Oregon Green and 14C-Aminoisobutyric acid followed by an indocyanine green vascular washout. Tracer accumulation was determined by quantitative fluorescent microscopy and quantitative autoradiography. Survival was tracked and tumor burden was monitored via bioluminescent imaging. Extent of mutation differences and acquired resistance was measured in-vitro through half-maximal inhibitory assays and qRT-PCR analysis.

Results
A PC-9 brain seeking line (PC-9-Br) was established. Mice inoculated with PC-9-Br resulted in a significantly decreased survival time compared with mice inoculated with parental PC-9. Non-targeted chemotherapy with cisplatin and etoposide (51.5 days) significantly prolonged survival of PC-9-Br brain metastases in mice compared to vehicle control (42 days) or cisplatin and pemetrexed (45 days). Further in-vivo imaging showed greater tumor vasculature in mice treated with cisplatin and etoposide compared to non-tumor regions, which was not observed in mice treated with vehicle or cisplatin and pemetrexed. More importantly, PC-9-Br showed significant resistance to gefitinib by in-vitro MTT assays (IC50>2.5 µM at 48hrs and 0.1 µM at 72hrs) compared with parental PC-9 (IC50: 0.75 µM at 48hrs and 0.027 µM at 72hrs). Further studies on the molecular mechanisms of gefitinib resistance revealed that EGFR and phospho-EGFR were significantly decreased in PC-9-Br compared with PC-9. Expression of E-cadherin and vimentin did not show EMT in PC-9-Br compared with parental PC-9, and PC-9-Br had neither T790 mutation nor amplifications of MET and HER2 compared with parental PC-9.

Conclusion
Our study demonstrated that brain metastases of lung cancer cells may independently prompt drug resistance without drug treatment.