bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and microbiological characteristics of Cryptococcus gattii isolated from 7 hospitals in China
Authors: Jin Liang , Cao Jing-Rong , Xue Xin-Ying , Wu Hua , Wang Li-Feng , Guo Ling , Shen Ding-Xia
Published: March 2020

Background

Infection, even outbreak, caused by Cryptococcus gattii (C. gattii) has been reported in Canada and the United States, but there were sparsely-reported cases of C. gattii in China. Our interest in occurrence, clinical manifestation, laboratory identification and molecular characterization of Chinese C. gattii strains leads us to this research.

Results

Out of 254 clinical isolates, initially identified as Cryptococcus neoformans (C. neoformans), eight strains were re-identified as C. gattii. Multi-locus sequence typing (MLST) showed genotype VGI accounted for the most (6 / 8), the other two strains were genotype VGII (VGIIa and VGIIb respectively) with 3 specific spectra of molecular weight about 4342, 8686, 9611 Da by MALDI-TOF MS. The minimal inhibitory concentrations (MICs) of Fluconazole with Yeast one was 2~4 times higher than that with ATB fungus 3 and MICs of antifungal agents against VGII strains were higher than against VGI strains. Comparative proteome analysis showed that 329 and 180 proteins were highly expressed by C. gattii VGI and VGII respectively. The enrichment of differentially expressed proteins was directed to Golgi complex.

Conclusions

Infection by C. gattii in China occurred sparsely. Genotype VGI was predominant but VGII was more resistant to antifungal agents. There was significant difference in protein expression profile between isolates of VGI and VGII C. gattii.
Identification and evolution of C4 photosynthetic pathway genes in plants
Authors: Shi Weiping , Yue Linqi , Guo Jiahui , Wang Jianming , Yuan Xiangyang , Dong Shuqi , Guo Jie , Guo Pingyi
Published: March 2020

Background

NADP-malic enzyme (NAPD-ME), and pyruvate orthophosphate dikinase (PPDK) are important enzymes that participate in C4 photosynthesis. However, the evolutionary history and forces driving evolution of these genes in C4 plants are not completely understood.

Results

We identified 162 NADP-ME and 35 PPDK genes in 25 species and constructed respective phylogenetic trees. We classified NADP-ME genes into four branches, A1, A2, B1 and B2, whereas PPDK was classified into two branches in which monocots were in branch I and dicots were in branch II. Analyses of selective pressure on the NAPD-ME and PPDK gene families identified four positively selected sites, including 94H and 196H in the a5 branch of NADP-ME, and 95A and 559E in the e branch of PPDK at posterior probability thresholds of 95%. The positively selected sites were located in the helix and sheet regions. Quantitative RT-PCR (qRT-PCR) analyses revealed that expression levels of 6 NADP-ME and 2 PPDK genes from foxtail millet were up-regulated after exposure to light.

Conclusion

This study revealed that positively selected sites of NADP-ME and PPDK evolution in C4 plants. It provides information on the classification and positive selection of plant NADP-ME and PPDK genes, and the results should be useful in further research on the evolutionary history of C4 plants.
Effect of arsenic stress on 5-methylcytosine, photosynthetic parameters and nutrient content in arsenic hyperaccumulator Pteris cretica (L.) var. Albo-lineata
Authors: Zemanová Veronika , Popov Marek , Pavlíková Daniela , Kotrba Pavel , Hnilička František , Česká Jana , Pavlík Milan
Published: March 2020

Background

Arsenic toxicity induces a range of metabolic responses in plants, including DNA methylation. The focus of this paper was on the relationship between As-induced stress and plant senescence in the hyperaccumulator Pteris cretica var. Albo-lineata (Pc-Al). We assume difference in physiological parameters and level of DNA methylation in young and old fronds as symptoms of As toxicity.

Results

The As accumulation of Pc-Al fronds, grown in pots of haplic chernozem contaminated with 100 mg As kg− 1 for 122 days, decreased with age. Content of As was higher in young than old fronds for variants with 100 mg As kg− 1 (2800 and 2000 mg As kg− 1 dry matter, respectively). The highest As content was determined in old fronds of Pc-Al grown in pots with 250 mg As kg− 1. The increase with age was confirmed for determined nutrients – Cu, Mg, Mn, S and Zn. A significant elevation of all analysed nutrients was showed in old fronds. Arsenic accumulation affected DNA methylation status in fronds, but content of 5-methylcytosine (5mC) decreased only in old fronds of Pc-Al (from 25 to 12%). Determined photosynthetic processes showed a decrease of fluorescence, photosynthetic rate and chlorophylls of As treatments in young and old fronds. Water potential was decreased by As in both fronds. Thinning of the sclerenchymatous inner cortex and a reduction in average tracheid metaxylem in the vascular cylinder was showed in roots of As treatment. Irrespective to fronds age, physiological parameters positively correlated with a 5mC while negatively with direct As toxicity. Opposite results were found for contents of Cu, Mg, Mn, S and Zn.

Conclusions

The results of this paper point to changes in the metabolism of the hyperaccumulator plant Pc-Al, upon low and high exposure to As contamination. The significant impact of As on DNA methylation was found in old fronds. Irrespective to fronds age, significant correlations were confirmed for 5mC and As toxicity. Our analysis of the very low water potential values and lignification of cell walls in roots showed that transports of assimilated metabolites and water between roots and fronds were reduced. As was showed by our results, epigenetic changes could affect studied parameters of the As hyperaccumulator plant Pc-Al, especially in old fronds.
Diffused hepatic angiosarcoma with Kasabach-Merritt syndrome-case report and literature review
Authors: Zhang Xing-mao , Tong Yao , Li Qing , He Qiang
Published: March 2020

Background

Hepatic angiosarcoma is a rare malignant tumor featured by highly aggressive behavior and poor prognosis. There are few reports about diffused hepatic angiosarcoma with Kasabach-Merritt syndrome till now.

Case presentation

A male patient with the chief complain of hepatic space-occupying lesion accompanied by disturbance of consciousness and jaundice. Hyperbilirubinemia, anemia, thrombocytopenia, prolonged prothrombin time, hypofibrinogenemia, decreased prothrombin activity, and increased fibrinogen degradation product and D-dimer were confirmed by blood analysis; multiple focal hypodense lesions in liver was detected by abdominal computed tomography. Liver failure and Kasabach-Merritt syndrome induced by hepatic hemangioma was diagnosed before operation and liver transplantation was performed. Hepatic angiosarcoma was finally proven by postoperative pathology. This patient died of tumor metastasis 2 months after operation.

Conclusions

Hepatic angiosarcoma which can generate Kasabach-Merritt syndrome and even liver failure has an extremely poor prognosis; liver transplantation option should not be considered in hepatic angiosarcoma regardless of the reason.
AMPI-AB validity and reliability: a multidimensional tool in resource-limited primary care settings
Authors: Saraiva Marcos Daniel , Venys Amanda Lagreca , Abdalla Fábio Luiz Pantaleão , Fernandes Mariana Seabra , Pisoli Priscila Henriques , Sousa Danilsa Margareth da Rocha Vilhena , Bianconi Barbara Lobo , Henrique Expedita Ângela , Garcia Vanessa Silva Suller , Maia Lucas Henrique de Mendonça , Suzuki Gisele Sayuri , Serrano Priscila Gonçalves , Hiratsuka Marcel , Szlejf Claudia , Jacob-Filho Wilson , Paschoal Sérgio Márcio Pacheco
Published: March 2020

Background

The early identification of individuals at high risk for adverse outcomes by a Comprehensive Geriatric Assessment (CGA) in resource-limited primary care settings enables tailored treatments, however, the evidence concerning its benefits are still controversial. The main objective of this study was to examine the validity and reliability of the “Multidimensional Assessment of Older People in Primary Care (AMPI-AB)”, a CGA for primary care in resource-limited settings.

Methods

Longitudinal study, with median follow-up time of 16 months. Older adults from a public primary care unit in São Paulo, Brazil, were consecutively admitted. Reliability was tested in a sample from a public geriatric outpatient clinic. Participants were classified by the AMPI-AB score as requiring a low, intermediate or high complexity of care. The Physical Frailty Phenotype was used to explore the AMPI-AB’s concurrent validity. Predictive validity was assessed with mortality, worsening of the functional status, hospitalizations, emergency room (ER) visits and falls. The area under the ROC curve and logistic regression were calculated for binary outcomes, and a Cox proportional hazards model was used for survival analysis.

Results

Older adults (n = 317) with a median age of 80 (74–86) years, 67% female, were consecutively admitted. At the follow-up, 7.1% of participants had died, and increased dependency on basic and instrumental activities of daily living was detected in 8.9 and 41.1% of the participants, respectively. The AMPI-AB score was accurate in detecting frailty (area under the ROC curve = 0.851), predicted mortality (HR = 1.25, 95%CI = 1.13–1.39) and increased dependency on basic (OR = 1.26, 95%CI = 1.10–1.46) and instrumental (OR = 1.22, 95%CI = 1.12–1.34) activities of daily living, hospitalizations (OR = 2.05, 95%CI = 1.04–1.26), ER visits (OR = 1.20, 95%CI = 1.10–1.31) and falls (OR = 1.10, 95%CI = 1.01–1.20), all models adjusted for sex and years of schooling. Reliability was tested in a sample of 52 older adults with a median age of 72 (85–64) years, 63.5% female. The AMPI-AB also had good interrater (ICC = 0.87, 95%CI = 0.78–0.92), test-retest (ICC = 0.86, 95%CI = 0.76–0.93) and proxy reliability (ICC = 0.84, 95%CI = 0.67–0.93). The Cronbach’s alpha was 0.69, and the mean AMPI-AB administration time was 05:44 ± 02:42 min.

Conclusion

The AMPI-AB is a valid and reliable tool for managing older adults in resource-limited primary care settings.
Google Health Trends performance reflecting dengue incidence for the Brazilian states
Authors: Romero-Alvarez Daniel , Parikh Nidhi , Osthus Dave , Martinez Kaitlyn , Generous Nicholas , del Valle Sara , Manore Carrie A.
Published: March 2020

Background

Dengue fever is a mosquito-borne infection transmitted by Aedes aegypti and mainly found in tropical and subtropical regions worldwide. Since its re-introduction in 1986, Brazil has become a hotspot for dengue and has experienced yearly epidemics. As a notifiable infectious disease, Brazil uses a passive epidemiological surveillance system to collect and report cases; however, dengue burden is underestimated. Thus, Internet data streams may complement surveillance activities by providing real-time information in the face of reporting lags.

Methods

We analyzed 19 terms related to dengue using Google Health Trends (GHT), a free-Internet data-source, and compared it with weekly dengue incidence between 2011 to 2016. We correlated GHT data with dengue incidence at the national and state-level for Brazil while using the adjusted R squared statistic as primary outcome measure (0/1). We used survey data on Internet access and variables from the official census of 2010 to identify where GHT could be useful in tracking dengue dynamics. Finally, we used a standardized volatility index on dengue incidence and developed models with different variables with the same objective.

Results

From the 19 terms explored with GHT, only seven were able to consistently track dengue. From the 27 states, only 12 reported an adjusted R squared higher than 0.8; these states were distributed mainly in the Northeast, Southeast, and South of Brazil. The usefulness of GHT was explained by the logarithm of the number of Internet users in the last 3 months, the total population per state, and the standardized volatility index.

Conclusions

The potential contribution of GHT in complementing traditional established surveillance strategies should be analyzed in the context of geographical resolutions smaller than countries. For Brazil, GHT implementation should be analyzed in a case-by-case basis. State variables including total population, Internet usage in the last 3 months, and the standardized volatility index could serve as indicators determining when GHT could complement dengue state level surveillance in other countries.
Joint modelling of longitudinal and time-to-event data: an illustration using CD4 count and mortality in a cohort of patients initiated on antiretroviral therapy
Authors: Mchunu Nobuhle N. , Mwambi Henry G. , Reddy Tarylee , Yende-Zuma Nonhlanhla , Naidoo Kogieleum
Published: March 2020

Background

Modelling of longitudinal biomarkers and time-to-event data are important to monitor disease progression. However, these two variables are traditionally analyzed separately or time-varying Cox models are used. The former strategy fails to recognize the shared random-effects from the two processes while the latter assumes that longitudinal biomarkers are exogenous covariates, resulting in inefficient or biased estimates for the time-to-event model. Therefore, we used joint modelling for longitudinal and time-to-event data to assess the effect of longitudinal CD4 count on mortality.

Methods

We studied 4014 patients from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) who initiated ART between June 2004 and August 2013. We used proportional hazards regression model to assess the effect of baseline characteristics (excluding CD4 count) on mortality, and linear mixed effect models to evaluate the effect of baseline characteristics on the CD4 count evolution over time. Thereafter, the two analytical approaches were amalgamated to form an advanced joint model for studying the effect of longitudinal CD4 count on mortality. To illustrate the virtues of the joint model, the results from the joint model were compared to those from the time-varying Cox model.

Results

Using joint modelling, we found that lower CD4 count over time was associated with a 1.3-fold increase in the risk of death, (HR: 1.34, 95% CI: 1.27-1.42). Whereas, results from the time-varying Cox model showed lower CD4 count over time was associated with a 1.2-fold increase in the risk of death, (HR: 1.17, 95% CI: 1.12-1.23).

Conclusions

Joint modelling enabled the assessment of the effect of longitudinal CD4 count on mortality while correcting for shared random effects between longitudinal and time-to-event models. In the era of universal test and treat, the evaluation of CD4 count is still crucial for guiding the initiation and discontinuation of opportunistic infections prophylaxis and assessment of late presenting patients. CD4 count can also be used when immunological failure is suspected as we have shown that it is associated with mortality.
Methicillin-resistant Staphylococcus aureus nasal colonization among HIV-infected patients in Taiwan: prevalence, molecular characteristics and associated factors with nasal carriage
Authors: Hsu Yi-Yu , Wu David , Hung Chien-Ching , Huang Shie-Shian , Yuan Fang-Hsueh , Lee Ming-Hsun , Huang Ching-Tai , Shie Shian-Sen , Huang Po-Yen , Yang Chien-Chang , Cheng Chun-Wen , Leu Hsieh-Shong , Wu Ting-Shu , Huang Yhu-Chering
Published: March 2020

Background

To evaluate nasal carriage, antibiotic susceptibility and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA), as well as the risk factors of MRSA colonization, in human immunodeficiency virus (HIV)-infected patients in northern Taiwan.

Methods

From September 2014 to November 2015, HIV-infected patients seeking outpatient care at four hospitals were eligible for this study. A nasal specimen was obtained from each subject for the detection of S. aureus and a questionnaire was completed by each subject. MRSA isolates once identified were characterized.

Results

Of 553 patients surveyed, methicillin-susceptible S. aureus (MSSA) was detected in 119 subjects (21.5%) and MRSA in 19 subjects (3.4%). Female gender, injection drug use, smoking, hepatitis C virus carrier, cancer and antibiotic use within 1 year were positively associated with MRSA colonization. By multivariate analysis, only cancer (adjust odds ratio (aOR) 7.78, [95% confidence interval (CI), 1.909–31.731]) and antibiotic use within 1 year (aOR 3.89, [95% CI, 1.219–12.433]) were significantly associated with MRSA colonization. Ten isolates were characterized as sequence type (ST) 59/staphylococcal chromosome cassette (SCC) IV or VT, endemic community strains in Taiwan, four isolates as ST 8/SCCmec IV (USA 300) and one isolate as ST 239/SCCmec IIIA, a hospital strain. All the community-associated MRSA isolates were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX).

Conclusions

Nasal MRSA carriage in HIV-infected patients seeking outpatient care was low (3.4%) in northern Taiwan. Most of the colonizing isolates were genetically endemic community strains and exhibited high susceptibility to TMP-SMX and fluoroquinolones. Cancer and antibiotic use within 1 year were associated with MRSA colonization.
Identification of novel biomarkers in ischemic stroke: a genome-wide integrated analysis
Authors: Xie Qizhi , Zhang Xiaoyun , Peng Sijia , Sun Jingjing , Chen Xiao , Deng Yuanfei , Yi Li
Published: March 2020

Background

Ischemic Stroke (IS) is the most common neurological emergency disease and has become the second most frequent cause of death after coronary artery disease in 2015. Owing to its high fatality rate and narrow therapeutic time window, early identification and prevention of potential stroke is becoming increasingly important.

Methods

We used meta-analysis and bioinformatics mining to explore disease-related pathways and regulatory networks after combining messengerRNA (mRNA) and miRNA expression analyses. The purpose of our study was to screen for candidate target genes and microRNA(miRNA) for early diagnosis of potential stroke.

Results

Five datasets were collected from the Gene Expression Omnibus (GEO) database by systematical retrieval, which contained three mRNA datasets (102 peripheral blood samples in total) and two miRNA dataset (59 peripheral blood samples). Approximately 221 different expression(DE) mRNAs (155 upregulated and 66 downregulated mRNAs) and 185 DE miRNAs were obtained using the metaDE package and GEO2R tools. Further functional enrichments of DE-mRNA, DE-miRNA and protein-protein interaction (PPI) were performed and visualized using Cytoscape.

Conclusion

Our study identified six core mRNAs and two regulated miRNAs in the pathogenesis of stroke, and we elaborated the intrinsic role of systemic lupus erythematosus (SLE) and atypical infections in stroke, which may aid in the development of precision medicine for treating ischemic stroke. However, the role of these novel biomarkers and the underlying molecular mechanisms in IS require further fundamental experiments and further clinical evidence.
Obesity-related loci in TMEM18, CDKAL1 and FAIM2 are associated with obesity and type 2 diabetes in Chinese Han patients
Authors: Kang Jing , Guan Ren-Chu , Zhao Ying , Chen Yan
Published: March 2020

Background

Several obesity susceptibility loci in genes, including GNPDA2, SH2B1, TMEM18, MTCH2, CDKAL1, FAIM2, and MC4R, have been identified by genome-wide association studies. The purpose of this study was to investigate whether these loci are associated with the concurrence of obesity and type 2 diabetes in Chinese Han patients.

Methods

Using the SNaPshot technique, we genotyped seven single nucleotide polymorphisms (SNPs) in 439 Chinese patients living in Northeast China who presented at The Second Hospital of Jilin University. We analyzed the associations between these seven alleles and clinical characteristics.

Results

Risk alleles near TMEM18 (rs6548238) were associated with increased waist circumference, waist/hip ratio, body mass index (BMI), fasting plasma glucose, hemoglobin A1c, diastolic blood pressure, triglycerides, total cholesterol, and low-density lipoprotein-cholesterol; risk alleles of CDKAL1 (rs7754840) were associated with increased waist circumference and waist/hip ratio; and FAIM2 (rs7138803) risk alleles were linked to increased BMI, diastolic blood pressure, and triglycerides (all P < 0.05). After adjusting for sex and age, loci near TMEM18 (rs6548238) and FAIM2 (rs7138803), but not SH2B1 (rs7498665), near GNPDA2 (rs10938397), MTCH2 (rs10838738) and near MC4R (rs12970134), were associated with increased risk for type 2 diabetes in obese individuals.

Conclusion

We found that loci near TMEM18 (rs6548238), CDKAL1 (rs7754840), and FAIM2 (rs7138803) may be associated with obesity-related indicators, and loci near TMEM18 (rs6548238) and FAIM2 (rs7138803) may increase susceptibility of concurrent type 2 diabetes associated with obesity.
Association between the IL-10 and IL-6 polymorphisms and brucellosis susceptibility: a meta-analysis
Authors: Jin Xiaochun , Wu Yueyuan , Yin Shuzhou , Chen Xu , Zhang Youtao
Published: March 2020

Background

Brucellosis is a quite normal zoonotic infection, which is caused by immediate contact with animals infected with Brucella or its products. IL-10 (− 1082 G/A, − 819 C/T, − 592C/A) and IL-6 -174 G/C polymorphisms have a great relationship with IL-10 and IL-6 production, which brings about Brucellosis pathogenesis and development. So far, the results of published literatures were controversial. Now, we perform a meta-analysis in different ethnic populations to get a more precise estimate of above polymorphisms with Brucellosis susceptibility.

Methods

Both OR and corresponding 95%CI were enrolled to make an assessment of the association strength through extracting genotyping frequency of cases and controls. The χ2-test based Q-statistic and I2statistics were applied. If there was no evident heterogeneity, the fixed-effects model would be applied. If not, the random-effects model would be used.

Results

The significant associations were only found in Asian population of − 819 loci under three genetic models as follows: (Allele model: OR = 0.60, 95%CI = 0.44–0.82,P = 0.001), (homozygote comparison: OR = 0.24, 95%CI = 0.09–0.62,P = 0.003), (recessive genetic model: OR = 0.22, 95%CI = 0.05–0.91,P = 0.036).

Conclusion

In conclusion, IL-10 − 819 loci polymorphism contributes no risk to Caucasian population but may be associated with decreased risk in Asian population. And IL-10 -1082 G/A, 592 loci and IL-6 -174 G/C polymorphism are not associated with Brucellosis risk.
Prevalence of postpartum depression and associated factors among postnatal care attendees in Debre Berhan, Ethiopia, 2018
Authors: Wubetu Abate Dargie , Engidaw Nigus Alemnew , Gizachew Kefyalew Dagne
Published: March 2020

Background

Postpartum depression explains various groups of depressive symptoms and syndromes that can take place during the first 6 weeks following birth. The postpartum period is a critical time where both mild and severe mood disorders can occur. The familiar forms are baby blues and postpartum depression. Understanding the prevalence and associated factors of postpartum depression is mandatory for early detection and treatment.

Methods

Institution based cross-sectional study was conducted from 1st May to June 30, 2018. The study participants were eligible women who came to Debre Berhan referral hospital and health centers for postnatal care and vaccination service. The Edinburgh postnatal depression scale was used to assess postpartum depression. A systematic random sampling technique was used to collect the data after determining the skip fraction (k = 2). The collected data were coded and entered into Epi-info version 7 and transported to SPSS version 20 for analysis. Both bivariate and multivariate binary logistic regression were done to identify associated factors. During bivariate analysis, variables with p-value < 0.05 were included in multivariate analysis. Odds ratios and their 95% confidence intervals were computed and variables with p-value less than 0.05 were considered to declare significantly associated factors (multivariate analysis).

Results

A total of 308 mothers who attended postpartum care we're included, which was a 100% response rate. The prevalence of postpartum depression was found to be 15.6% (95%CI = 11.7, 19.8). Being widowed/widower, having poor social support, having a current hospitalized child, and experienced a death of family member or close relative were significantly associated with postpartum depression.

Conclusions

The prevalence of postpartum depression was lower than most studies done in different areas. Major life events and traumas are associated with an increased risk of postpartum depression. Health professionals should be aware of the mother’s circumstances during the puerperium, they should initiate support to reduce the risk of depression in the postpartum period. Health care professionals working postpartum care clinics should give special attention to mothers who are widowed/widower, have poor social support, have a current hospitalized children, and experienced a death of family member or close relative.
Trends of stillbirth among reproductive-age women in Ethiopia based on Ethiopian demographic and health surveys: a multivariate decomposition analysis
Authors: Tesema Getayeneh Antehunegn , Gezie Lemma Derseh , Nigatu Solomon Gedlu
Published: March 2020

Background

Despite the effort to reduce stillbirth, Ethiopia remains one of the countries with the highest rate in the world. Therefore, this study aimed to analyze the trends of stillbirth among births from reproductive age women over time based on Ethiopian Demographic and Health Surveys (EDHSs).

Methods

Secondary data analysis was conducted based on the Ethiopian Demographic Health Surveys (EDHSs) conducted in 2005, 2011 and 2016. A total weighted sample of 12,037, 10,588, and 11,375 in 2005, 2011 and 2016 respectively were included for analysis. Trend and Logistic based decomposition analysis technique was used for analyzing the trends of stillbirth over time and factors contributing to the change in stillbirth rate. STATA 14 was employed for data management and analyses. All analyses presented in this paper were weighted for the sampling probabilities and non-response. Complex sampling procedures were also considered during testing of statistical significance.

Results

Among women of reproductive age, the stillbirth rate declined from 13.3/1000 births in 2005 to 9.2 per 1000 births in 2016 with the annual rate of reduction of 3.1%. The study found that the stillbirth rate has been declined over time concerning the place of residence, region, antenatal care, education and place of delivery. The decomposition analysis indicated that about 82.3% of the overall change stillbirth rate was due to the difference in women’s composition. Particularly, an increase in women’s urban place of residence, health facility delivery, and cesarean delivery were significant predictors for the decline in stillbirth rate over the surveys.

Conclusions

The stillbirth rate has been declined over time. More than 3/4th of the decrease in stillbirth rate was due to the difference in characteristics of women over the surveys. The increase in women’s urban place of residence, an increase in cesarean delivery and health facility delivery significantly contributed to the decrease in stillbirth rate over time. Public health interventions targeting rural resident women, strengthening emergency obstetric services and health facility delivery would help to maintain the decreasing trend of stillbirth rate in Ethiopia.
Evaluation of cinnamon extract effects on clbB gene expression and biofilm formation in Escherichia coli strains isolated from colon cancer patients
Authors: Kosari Faezah , Taheri Mohammad , Moradi Abbas , Hakimi Alni Reza , Alikhani Mohammad Yousef
Published: March 2020

Background

Colon cancer is one of the most common malignancies and the fourth leading cause of cancer-related mortality in the world. Colibactin, which is synthesized by the pks genomic island of E. coli interfere with the eukaryotic cell cycle. Cinnamon has an antimicrobial effect and considered as a colon cancer-preventing agent. The aim of the study was to evaluate the effects of cinnamon extract and cinnamaldehyde on clbB gene expression and biofilm formation in clinical isolates of E. coli.

Methods

Thirty E. coli carrying pks gene were isolated from the colon cancer patients, inflammatory bowel disease and healthy subjects. Antibiotic susceptibility was evaluated by disk diffusion method and the minimum inhibitory concentration of cinnamon essential oil and cinnamaldehyde by microdilution broth method. In vitro biofilm formation of E.coli isolates was monitored using a microtiter plate method. The presence of clbB, clbA and clbQ genes in E.coli isolates were evaluated by PCR. The effect of cinnamaldehyde and cinnamon essential oil on clbB gene expression was evaluated by Real-Time PCR.

Results

The highest antibiotic resistance was obtained with 94.4% for ticarcillin-clavulanic acid, azithromycin, amoxicillin, and amikacin. The MIC for all clinical isolates was 32 μl/ml of cinnamon essential oil and the MIC of cinnamaldehyde was between 0.00002 to 0.03 μl/ml. After exposure of isolates to cinnamon extract and cinnamaldehyde, 40 and 13.3% were weakly biofilm producers, respectively. The frequencies of clbB, clbA, and clbQ genes were 23.3, 23.3, and 26.7%, respectively. The expression of clbB gene in the presence of the Sub-MIC concentration of cinnamon essential oil and cinnamaldehyde was decreased in 8 isolates compared to untreated isolates (p-value < 0.05).

Conclusions

The antibacterial activity of cinnamaldehyde and cinnamon essential oil allows the use of these herbal compounds for treatment or supplements in infections caused by E. coli and in patients with suspected colorectal cancer.
Real-world treatment and survival of patients with advanced non-small cell lung Cancer: a German retrospective data analysis
Authors: Hardtstock Fränce , Myers David , Li Tracy , Cizova Diana , Maywald Ulf , Wilke Thomas , Griesinger Frank
Published: March 2020

Background

The objective of this study was to describe the real-world treatment and overall survival (OS) of German patients with a diagnosis of advanced non-small cell lung cancer (aNSCLC), and to explore factors associated with the real-world mortality risk.

Methods

This was a retrospective German claims data analysis of incident aNSCLC patients. Data were available from 01/01/2011 until 31/12/2016. Identification of eligible patients took place between 01/01/2012–31/12/2015, to allow for at least 1-year pre-index and follow-up periods. Inpatient and outpatient mutation test procedures after aNSCLC diagnosis were observed. Further, prescribed treatments and OS since first (incident) aNSCLC diagnosis and start of respective treatment lines were described both for all patients and presumed EGFR/ALK/ROS-1-positive patients. Factors associated with OS were analyzed in multivariable Cox regression analysis.

Results

Overall, 1741 aNSCLC patients were observed (mean age: 66·97 years, female: 29·87%). The mutation test rate within this population was 26·31% (n = 458), 26·6% of these patients (n = 122) received a targeted treatment and were assumed to have a positive EGFR/ALK/ROS-1 test result. Most often prescribed treatments were pemetrexed monotherapy as 1 L (21·23% for all and 11·11% for mutation-positive patients) and erlotinib monotherapy as 2 L (25·83%/38·54%). Median OS since incident diagnosis was 351 days in all and 571 days in mutation-positive patients. In a multivariable Cox regression analysis, higher age, a stage IV disease, a higher number of chronic drugs in the pre-index period and no systemic therapy increased the risk of early death since first aNSCLC diagnosis. On the other hand, female gender and treatment with therapies other than chemotherapy were associated with a lower risk of early death.

Conclusions

Despite the introduction of new treatments, the real-world survival prognosis for aNSCLC patients remains poor if measured based on an unselected real-world population of patients. Still, the majority of German aNSCLC patients do not receive a mutation test.
Quality of life study of patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma treated with gemcitabine+nab-paclitaxel versus gemcitabine alone: AX-PANC-SY001, a randomized phase-2 study
Authors: Yalcin Suayib , Dane Faysal , Oksuzoglu Berna , Ozdemir Nuriye Yildirim , Isikdogan Abdurrahman , Ozkan Metin , Demirag Guzin Gonullu , Coskun Hasan Senol , Karabulut Bulent , Evrensel Turkkan , Ustaoglu Mehmet Ali , Ozdemir Feyyaz , Turna Hande , Yavuzsen Tugba , Aykan Faruk , Sevinc Alper , Akbulut Hakan , Yuce Deniz , Hayran Mutlu , Kilickap Saadettin
Published: March 2020

Background

Combination of gemcitabine and nab-paclitaxel has superior clinical efficacy than gemcitabine alone. Nevertheless, health-related quality of life. (QoL) associated with this combination therapy when administered at first-line in advanced pancreatic adenocarcinoma is unknown.

Methods

A total of 125 patients were randomized to combination therapy (1000 mg/m2 gemcitabine + 125 mg/m2 nab-paclitaxel) and single-agent gemcitabine (1000 mg/m2) arms to take treatment weekly for 7 of 8 weeks, and following 3 of 4 weeks, until progression or severe toxicity. Primary endpoints were three-months of definitive deterioration free percent of patients, and QoL.

Results

Overall QoL analyses showed that 34 and 58.3% of cases in gemcitabine and gemcitabine+nab-P arms had no deterioration in 3rd month QoL scores (p = 0.018). These proportions were 27.3 and 36.6% in 6th month assessments, respectively (p = 0.357). Median overall survivals in combination and single-agent arms were 9.92 months and 5.95 months, respectively (HR: 0.64, 95% CI: 0.42–0.86, p = 0.038). Median progression free survivals in these treatment arms were 6.28 and 3.22 months, respectively (HR: 0.58, 95% CI: 0.39–0.87, p = 0.008). Median time-to-deterioration were 5.36 vs 3.68 months, and objective response rates were 37.1% vs 23.7% (p = 0.009), respectively in combination and single-agent arms.

Conclusions

Combination therapy with gemcitabine + nab-paclitaxel had better overall and progression-free survival than gemcitabine alone. Also, combination therapy showed increased response rate without toxicity or deteriorated QoL. Combination treatment with gemcitabine and nab-paclitaxel may provide significant benefit for advanced pancreatic cancer.

Trial registration

This study has been registered in ClinicalTrials.gov as NCT03807999 on January 8, 2019 (retrospectively registered).
Downregulation of S100 calcium binding protein A12 inhibits the growth of glioma cells
Authors: Lu Chunhe , Liu Jia , Yao Mingze , Li Lun , Li Guangyu
Published: March 2020

Background

S100 calcium binding protein A12 (S100A12) is a member of the S100 protein family and is widely expressed in neutrophil and low expressed in lymphocytes and monocyte. However, the role of S100A12 in glioma has not yet been identified.

Methods

In the present study, we carried out immunohistochemical investigation of S100A12 in 81 glioma tissues to determine the expression of S100A12 in glioma cells, and evaluate the clinical significance of S100A12 in glioma patients. Futher we knockdown the S100A12 by shRNA, and evaluated cell proliferation, cell migration and cell apoptosis by MTT, colony formation assay, transwell assay,flow cytometry assa and western blot.

Results

We found that S100A12 was upregulated in tissues of glioma patients and the expression was correlated to WHO stage and tumor size. Further, we found that knockdown S100A12 inhibits the proliferation, migration and invasion of glioma cells through regulating cell apoptosis and EMT.

Conclusion

S100A12 plays a vital role in glioma progression, and may be an important regulatory molecule for biological behaviors of glioma cell lines.
The A818–6 system as an in-vitro model for studying the role of the transportome in pancreatic cancer
Authors: Tawfik Doaa , Zaccagnino Angela , Bernt Alexander , Szczepanowski Monika , Klapper Wolfram , Schwab Albrecht , Kalthoff Holger , Trauzold Anna
Published: March 2020

Background

The human pancreatic cancer cell line A818–6 can be grown in vitro either as a highly malignant, undifferentiated monolayer (ML) or as three-dimensional (3D) single layer hollow spheres (HS) simulating a benign, highly differentiated, duct-like pancreatic epithelial structure. This characteristic allowing A818–6 cells to switch from one phenotype to another makes these cells a unique system to characterize the cellular and molecular modifications during differentiation on one hand and malignant transformation on the other hand. Ion channels and transport proteins (transportome) have been implicated in malignant transformation. Therefore, the current study aimed to analyse the transportome gene expression profile in the A818–6 cells growing as a monolayer or as hollow spheres.

Methods & Results

The study identified the differentially expressed transportome genes in both cellular states of A818–6 using Agilent and Nanostring arrays and some targets were validated via immunoblotting. Additionally, these results were compared to a tissue Affymetrix microarray analysis of pancreatic adenocarcinoma patients’ tissues. The overall transcriptional profile of the ML and HS cells confirmed the formerly described mesenchymal features of ML and epithelial nature of HS which was further verified via high expression of E-cadherin and low expression of vimentin found in HS in comparison to ML. Among the predicted features between HS and ML was the involvement of miRNA-9 in this switch. Importantly, the bioinformatics analysis also revealed substantial number (n = 126) of altered transportome genes. Interestingly, three genes upregulated in PDAC tissue samples (GJB2, GJB5 and SLC38A6) were found to be also upregulated in ML and 3 down-regulated transportome genes (KCNQ1, TRPV6 and SLC4A) were also reduced in ML.

Conclusion

This reversible HS/ML in vitro system might help in understanding the pathophysiological impact of the transportome in the dedifferentiation process in pancreatic carcinogenesis. Furthermore, the HS/ML model represents a novel system for studying the role of the transportome during the switch from a more benign, differentiated (HS) to a highly malignant, undifferentiated (ML) phenotype.
Perineural invasion as a prognostic factor for intrahepatic cholangiocarcinoma after curative resection and a potential indication for postoperative chemotherapy: a retrospective cohort study
Authors: Zhang Zeyu , Zhou Yufan , Hu Kuan , Wang Dong , Wang Zhiming , Huang Yun
Published: March 2020

Background

In the past four decades, the incidence of cholangiocarcinoma, especially intrahepatic cholangiocarcinoma (ICC), has raised rapidly worldwide. Completeness of resection, max size of tumor and etc. are widely recognized as prognostic factors. However, the prognosis significance of perineural invasion (PNI) on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is controversial.

Methods

ICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Patients were grouped by existence of PNI and outcomes were compared between groups. The potential relationship between PNI and postoperative chemotherapy was also investigated.

Results

There was no significant difference in demographic, clinical staging or tumor index between two groups, except positive hepatitis B surface antigen and CA19–9. PNI negative group showed a better prognosis in RFS (P < 0.0001) and OS (P < 0.0001). COX regression analyses showed PNI as an independent risk factor in RFS and OS. ICC with postoperative chemotherapy showed better effects in the whole cohort on both RFS (P = 0.0023) and OS (P = 0.0011). In PNI negative group, postoperative chemotherapy also showed significant benefits on RFS and OS, however not in PNI positive group (P = 0.4920 in RFS andP = 0.8004 in OS).

Conclusion

PNI was an independent risk factor in R0-resected ICC, presenting worse recurrence and survival outcomes. Meanwhile, negative PNI may act as an indication of postoperative chemotherapy.
Long non-coding RNA AFAP1-AS1 accelerates the progression of melanoma by targeting miR-653-5p/RAI14 axis
Authors: Liu Fei , Hu Lanting , Pei Yi , Zheng Ke , Wang Wei , Li Shenglong , Qiu Enduo , Shang Guanning , Zhang Jiaming , Zhang Xiaojing
Published: March 2020

Background

Melanoma is the most aggressive skin cancer that derived from pigment cells, accounting for the majority of the skin-cancer-related deaths. Despite great development and evolution have been made in surgery, radiotherapy and adjuvant chemotherapy, the prognosis of melanoma patients exhibited no significant improvement. Long noncoding RNAs (lncRNAs) are frequently dysregulated and involved in the development of cancers. LncRNA AFAP1-AS1 has been explored in various cancers, whereas its role and regulatory mechanism in melanoma are not well understood.

Methods

The expression of AFAP1-AS1 was detected by qRT-PCR. CCK-8, colony formation, transwell and western blot assays were performed to investigate the biological role of AFAP1-AS1 in melanoma. Male BALB/c nude mice were applied for in vivo experiments. The interaction among AFAP1-AS1, miR-653-5p and RAI14 was investigated by RNA pull down, RIP and luciferase reporter assays.

Results

AFAP1-AS1 was highly expressed in melanoma cell lines. Suppression of AFAP1-AS1 impaired cell proliferation, migration, invasion and EMT in melanoma. Moreover, AFAP1-AS1 was a ceRNA of RAI14 by competitively binding with miR-653-5p. Besides, miR-653-5p overexpression or RAI14 inhibition could repress tumor growth. Eventually, rescue assays indicated that the function of AFAP1-AS1 in the cellular process of melanoma was dependent on miR-653-5p and RAI14.

Conclusions

AFAP1-AS1 exerts its oncogenic function in melanoma by targeting miR-653-5p/RAI14 axis.
Preoperative anxiety in adults - a cross-sectional study on specific fears and risk factors
Authors: Eberhart Leopold , Aust Hansjörg , Schuster Maike , Sturm Theresa , Gehling Markus , Euteneuer Frank , Rüsch Dirk
Published: March 2020

Background

Preoperative anxiety comprising anesthesia and surgery related anxiety is common and perceived by many patients as the worst aspect of the surgical episode. The aim of this study was to identify independent predictors of these three anxieties dimensions and to quantify the relevance of specific fears particularly associated with anesthesia.

Methods

This study was part of a cross-sectional survey in patients scheduled to undergo elective surgery. Anxiety levels were measured with the Amsterdam Preoperative Anxiety and Information Scale (APAIS). Modified numeric rating scales (mNRS, range 0–10) were used to assess the severity of eight selected specific fears which were predominantly analyzed descriptively. Multivariate stepwise linear regression was applied to determine independent predictors of all three anxiety dimensions (APAIS anxiety subscales).

Results

3087 of the 3200 enrolled patients were analyzed. Mean (SD) total preoperative anxiety (APAIS-A-T, range 4–20) was 9.9 (3.6). High anxiety (APAIS-A-T > 10) was reported by 40.5% of subjects. Mean (SD) levels of concern regarding the eight studied specific fears ranged from 3.9 (3.08) concerning “Anesthesiologist error” to 2.4 (2.29) concerning “Fatigue and drowsiness” with an average of 3.2 (2.84) concerning all specific fears. Ranking of all specific fears according to mean mNRS scores was almost identical in patients with high versus those with low anxiety. Among nine independent predictors of anxiety, only 3 variables (female gender, negative and positive anesthetic experience) independently predicted all three APAIS anxiety subscales. Other variables had a selective impact on one or two APAIS anxiety subscales only. Female gender had the strongest impact on all three APAIS anxiety subscales. Adjusted r2values of the three models were all below 13%.

Conclusions

The high variability of importance assigned to all specific fears suggests an individualized approach is advisable when support of anxious patients is intended. Considering independent predictors of anxiety to estimate each patient’s anxiety level is of limited use given the very low predictive capacity of all three models. The clinical benefit of dividing patients into those with high and low anxiety is questionable.

Trial registration

German Registry of Clinical Trials (DRKS00016725), retrospectively registered.
Knowledge level of cancer symptoms and risk factors in the Gaza Strip: a cross-sectional study
Authors: Elshami Mohamedraed , Elshami Alaa , Alshorbassi Nabeela , Alkhatib Mohammed , Ismail Iyad , Abu-Nemer Khitam , Hana Mustafa , Qandeel Ahmed , Abdelwahed Ahmed , Yazji Hamza , Abuamro Hisham , Matar Ghadeer , Alsahhar Ahmed , Abolamzi Ahmed , Baraka Obay , Elblbessy Mahmood , Samra Tahani , Bottcher Bettina
Published: March 2020

Background

In low-income settings, cancer is often diagnosed in advanced stages due to late presentation. Good public awareness of cancer signs and symptoms has a positive impact on the time patients take before they present to healthcare professionals. Therefore, this study examined public knowledge of cancer signs and symptoms as well as risk factors in Gaza.

Methods

This was a cross-sectional study. Participants were recruited from adult visitors (≥18 years) to governmental hospitals covering all five governorates of Gaza, and adolescent students (15 to 17 years) from 10 high schools in corresponding locations. An Arabic version of the Cancer Awareness Measure (CAM) was completed in a face-to-face interview. It described demographic data and knowledge of: cancer prevalence, age-related risk, signs and symptoms as well as risk factors both in recall and recognition questions.

Results

Of 3033 participants invited, 2886 completed the CAM (response rate = 95.2%). Adult mean age ± standard deviation was 33.7 ± 11.7 years and that of adolescents was 16.3 ± 0.8 years. Half of the participants (n = 1457, 50.5%) were adolescent (781 females; 53.6%) and 1429 (49.5%) were adult (702 females; 49.1%). About two thirds (n = 1885) thought about cancer as unrelated to age. Only 196 participants (6.8%) identified colorectal cancer as the most common cancer among men. Awareness of cancer signs/symptoms was poor to fair, where ‘lump’ was most commonly recognized (n = 2227, 77.2%) and ‘change of bowel habit’ the least (n = 670, 23.2%). Only 217 participants (7.5%) had a good level of recognizing risk factors with ‘smoking’ being the most identified and ‘eating less than five portions of fruits and vegetables a day’ the least. There was a higher likelihood for adults to identify most cancer signs/symptoms and risk factors than adolescents, except for recalling ‘unexplained pain’, ‘persistent cough/hoarseness’, ‘non-healing ulcer’, ‘smoking’, and ‘eating less than five portions of fruits and vegetables a day’.

Conclusion

Public awareness of cancer signs/symptoms and risk factors needs to improve to facilitate early presentation and diagnosis in Gaza. Combining the delivery of public campaigns with tailored education to population groups, including the youth, may increase their knowledge and maintain its impact.