bluuebunny/crossref_metadata_2025_split huggingface dataset:
1-Methyl-D-tryptophan activates aryl hydrocarbon receptor, a pathway associated with bladder cancer progression
Authors: Dellê Humberto , Matheus Luiz Henrique Gomes , Dalmazzo Stephanie Vanin , Brito Rodrigo Barbosa Oliveira , Pereira Lucas Alves , Almeida Robson José , Camacho Cleber Pinto 
Published: June 2020

Abstract
Background
Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising target for immunotherapy in bladder cancer (BC). IDO1 breaks-down tryptophan to generate kynurenine derivates, which may activate the aryl hydrocarbon receptor (AHR). AHR is an important target for carcinogens, but its association with BC progression was unknown. Two IDO1 inhibitors used in clinical trials are 1-methyl-D-tryptophan (MT) and INCB240360. Because MT is an aromatic hydrocarbon, it may be a ligand for AHR. We hypothesized that AHR could be associated with BC progression and that MT could activate AHR in BC.
Methods
BC patients (n = 165) were selected from the Gene Expression Omnibus database. A cutoff point for relative expression of AHR and cytochrome 450 enzymes (CYP1A1, CYP1A2, and CYP1B1; markers of AHR activation) was determined to compare with the grade, stage, and tumor progression. For in vitro experiments, RT4 (grade 1) and T24 (grade 3) BC cells were incubated with MT and INCB240360 to evaluate the expression of AHR and CYP1A1.
Results
AHR activation was associated with grade, stage, and progression of BC. T24 cells express higher CYP1A1 than RT4 cells. Although IDO1 expression and kynurenine production are elevated in T24 cells concomitantly to CYP1A1 expression, IDO1 inhibitors were not able to decrease CYP1A1 expression, in contrast, MT significantly increased it in both cell lines.
Conclusion
In conclusion, it is rational to inhibit IDO1 in BC, among other factors because it contributes to AHR activation. However, MT needs to be carefully evaluated for BC because it is an AHR pathway agonist independently of its effects on IDO1.
Gene modules and non-coding RNAs involved in pancreatic tumorigenesis through acinar ductal metaplasia
Authors: Zhang Huairong , Shi Bingyin , GAO ZU-HUA , GAO BO 
Published: June 2020

Abstract
Background

Acinar ductal metaplasia (ADM) can progress through pancreatic ductal carcinoma in situ (PanIN) to pancreatic ductal adenocarcinoma (PDAC). However, the genetic alterations and its transcriptional regulators during the process of ADM-driven PDAC tumorigenesis are largely unknown. Therefore, we applied a multidimensional integration strategy to unveil the gene modules and non-coding RNAs that drives the ADM-PanIN-PDAC process.
Methods

GSE40895 and the microarray datasets were integrated to unmask the regulators link ADM, PanIN and PDAC. Based on the differential expressed genes and protein–protein interaction (PPI) networks for each stage, Overlap and crosstalk gene modules in ADM-PanIN-PDAC were identified using STRING and Cytoscape. Function of these modules were elucidated by gene ontology analysis. Expression level of hub genes and survival analysis were investigated in human PDAC via GEPIA. MiRDB database was applied to predict potential non-coding RNAs (ncRNAs) capable of regulating overlap and crosstalk genes.
Results

We found several bridging ADM gene modules (e.g. SMARCA1 and H2AFZ), PanIN gene modules (e.g. HDAC11 and SMARCA2) and PDAC gene modules (e.g. OLFR239 and CLIP3). They were enriched in in nucleosome assembly, chromatin organization and G-protein coupled receptor signaling pathway by GO analysis. MicroRNAs (e.g. mmu-miR-335-5p and mmu-miR-669n) and lncRNAs (e.g. H19 and Gm14207) took part in this ample crosstalk by regulating the gene expression.
Conclusions

SMARCA1, SMARCA2 and CLIP3 were identified as novel crosstalk genes and significant prognostic biomarkers, providing new insights into ADM-driven PDAC carcinogenesis. Transcriptional regulatory non-coding RNAs targeting crosstalk and overlap genes appear promising for early PDAC intervention.
A cluster-randomized trial of workplace ergonomics and neck-specific exercise versus ergonomics and health promotion for office workers to manage neck pain—a secondary outcome analysis
Authors: Johnston Venerina , Chen Xiaoqi , Welch Alyssa , Sjøgaard Gisela , Comans Tracy A , McStea Megan , Straker Leon , Melloh Markus , Pereira Michelle , O'Leary Shaun 
Published: June 2020

Abstract
Background: Neck pain is prevalent among office workers. This study evaluated the impact of an ergonomic and exercise training (EET) intervention and an ergonomic and health promotion (EHP) intervention on neck pain intensity among the general office workers and a subgroup of office workers with neck pain at baseline. Methods: A prospective 12-month cluster-randomized trial was conducted in 14 public and private organisations. Participants were office workers, aged ≥18 years working ≥30 hours per week (n=740). All participants received an individualised workstation ergonomic intervention, followed by 1:1 allocation to the EET group (neck-specific exercise training), or the EHP group (health promotion) for 12 weeks. Neck pain intensity (scale: 0-9) was recorded at baseline, 12 weeks, and 12 months. Participants with data at these three time points were included for analysis (n=367). Intervention group differences were analysed using generalized estimating equation models on an intention-to-treat basis and adjusted for potential confounders (demographic, health or work-related). Subgroup analysis was performed on participants symptomatic at baseline (neck cases) (n=96).Results: The EET group demonstrated significantly greater reductions in neck pain intensity at 12 weeks compared to the EHP group for both the general office workers (EET: b=-0.53 points 95%CI: -0.84– -0.22 [36%] and EHP: b=-0.17 points 95%CI: -0.47–0.13 [10.5%], p-value=0.02) and neck cases subgroup (EET: b=-2.32 points 95%CI: -3.09– -1.56 [53%] and EHP: b=-1.75 points 95%CI: -2.35– -1.16 [36%], p=0.04). Reductions in pain intensity were not maintained at 12 months with no between-group differences observed in either the general office workers (EET: b=-0.18, 95%CI: -0.53–0.16 and EHP: b=-0.14 points 95%CI: -0.49–0.21, p=0.53) or neck cases subgroup, although in both groups an overall reduction was found (EET: b= -1.61 points 95%CI: -2.36– -0.89 and EHP: b=-1.9 points 95%CI: -2.59– -1.20, p=0.26). Conclusion: EET was more effective and clinically meaningful than EHP in reducing neck pain intensity in both general office workers and those with neck pain immediately following the intervention period (12 weeks) but not at 12 months follow-up. Findings suggest the need for continuation of exercise to maintain benefits in the longer term.Clinical trial registration: ACTRN12612001154897 Date of Registration: 31/10/2012
Malaria outbreak in Riaba district, Bioko Island, in 2019 – Lessons learnt
Authors: Guerra Carlos A , Fuseini Godwin , Donfack Oliver Tresor , Smith Jordan M , Mifumu Teresa Ayingono Ondo , Akadiri Gninoussa , Eyang Delicias Esono Mba , Eburi Consuelo Oki , Vaz Liberato Motobe , Micha Víctor Mba , Okenve Leonor Ada , Janes Christopher R , Andeme Ramona Mba , Rivas Matilde Riloha , Phiri Wonder P , Slotman Michel A , Smith Dave L , García Guillermo Alberto 
Published: June 2020

Abstract
A sudden surge in malaria cases was observed in the district of Riaba, Bioko Island, at the start of 2019. Between January and April, confirmed malaria cases and malaria incidence increased about three-fold compared to the same period in 2018. Concurrently, anopheline human biting rate (HBR) increased 2.1-fold. During the outbreak, 82.2% of the district population was tested for malaria with a rapid diagnostic test and 37.2% were found positive and treated according to national guidelines. Vector control interventions, including indoor residual spraying and larval source management were scaled-up in response. After the interventions, the number of confirmed cases decreased by 70% and the overall parasite prevalence in the communities by 43.8%. Observed prevalence in a follow up malaria indicator survey, however, was significantly higher than elsewhere on the island and higher than in previous years. There was no significant reduction in HBR, which remained high for the rest of the year. The surge was attributed to various factors, chiefly increased rainfall and a large number of anthropogenic anopheline breeding sites created by construction works. This case study illustrates the need for sustained vector control interventions and multi-sector participation, particularly in malaria control settings with persistently high receptivity to local transmission.
Estimating cases of severe malaria at the population-level: Analysis of household surveys from 19 malaria endemic countries in Africa
Authors: Taylor Cameron , NAMASTE Sorrel ML , LOWELL Joanna , USEEM Johanna , YÉ Yazoumé 
Published: June 2020

Abstract
Background

The burden of severe malaria is uncertain at the population level because existing estimates rely exclusively on data from the formal healthcare system. Using data from population-based surveys this analysis examines severe malaria cases at the population level, which captures children whose caregivers 1) have taken the child to a healthcare facility but the child’s illness did not resolve, or 2) have not sought care for the child’s illness. Direct inclusion of these children in severe malaria estimates has been an underlying data gap.
Methods

This analysis examined data from 37 Demographic and Health Surveys and Malaria Indicator Surveys across 19 countries in sub-Saharan Africa collected between 2011 and 2018. The outcome of interest is severe malaria, defined as children age 6–59 months who were positive for malaria with at least one self-reported symptom for severe malaria, including loss of consciousness, rapid breathing, seizures, or severe anemia. The study includes a weighted descriptive, country-level analysis and a multilevel mixed-effects logistic regression model to assess the determinants of severe malaria.
Results

Among children positive for malaria across all surveys, 4.5% (95% CI 4.1–4.8) had at least one symptom of severe malaria, which was significantly associated with age, residence, wealth, and survey timing at a p-value less than 0.05. Children in the higher malaria transmission zone were more likely to have symptoms compared to those in the lowest transmission zone; however, these results were not statistically significant.
Conclusion

An accurate estimate of the burden of severe malaria is essential to assessing the impact of malaria interventions and to guiding future malaria investments. This analysis presents a novel approach of estimating the burden of severe malaria in children under age five in malaria endemic countries. Estimating severe malaria through household-based surveys allows countries to estimate severe malaria across time and to compare with other countries. Having a population level estimate of severe malaria helps further our understanding of the burden and epidemiology of severe malaria.
Day Time, Night Time, Over Time: Geographic and Temporal Uncertainty When Linking Event and Contextual Data
Authors: Folch David C , Fowler Christopher S , Mikaelian Levon 
Published: June 2020

Abstract
Background: The growth of geolocated data has opened the door to a wealth of new research opportunities in the health fields. One avenue of particular interest is the relationship between the spaces where people spend time and their health outcomes. This research model typically intersects individual data collected on a specific cohort with publicly available socioeconomic or environmental aggregate data. In spatial terms: individuals are represented as points on map at a particular time, and context is represented as polygons containing aggregated or modeled data from sampled observations. Uncertainty abounds in these kinds of complex representations.Methods: We present four sensitivity analysis approaches that interrogate the stability of spatial and temporal relationships between point and polygon data. Positional accuracy assesses the significance of assigning the point to the correct polygon. Neighborhood size investigates how the size of the context assumed to be relevant impacts observed results. Life course considers the impact of variation in contextual effects over time. Time of day recognizes that most people occupy different spaces throughout the day, and that exposure is not simply a function residential location. We use eight years of point data from a longitudinal study of children living in rural Pennsylvania and North Carolina and eight years of air pollution and population data presented at 0.5 mile (0.805 km) grid cells. We first identify the challenges faced for research attempting to match individual outcomes to contextual effects, then present methods for estimating the effect this uncertainty could introduce into an analysis and finally contextualize these measures as part of a larger framework on uncertainty analysis.Results: Spatial and temporal uncertainty is highly variable across the children within our cohort and the population in general. For our test datasets, we find greater uncertainty over the life course than in positional accuracy and neighborhood size. Time of day uncertainty is relatively low for these children.Conclusions: Spatial and temporal uncertainty should be considered for each individual in a study since the magnitude can vary considerably across observations. The underlying assumptions driving the source data play an important role in the level of measured
Attitude and Beliefs About Surgical Safety Checklist in a North Indian Tertiary Care Hospital a Decade Later of WHO Checklist
Authors: Bains Lovenish , Mishra Anurag , Kaur Daljit , Lal Pawan , Gupta Lalit , Malhotra Vikas 
Published: June 2020

Abstract
Avoidable surgical complications account for a large proportion of preventable medical injuries and deaths globally. Surgical Safety Checklist is evidence-based, internationally accepted valid instrument, which has been found to reduce postoperative morbidity and mortality; the benefits of which are most striking in low- and middle-income countries (LMICs) Despite implementation in many hospitals throughout the country, there is still lack of awareness and concern in many LMICS health care facilities towards SSCL and its use, even after a decade of WHO checklist. We conducted a survey to assess the knowledge, attitudes and beliefs about the WHO-surgical checklist in which 65.4% (138) surgeons, 25.1% (53) anaesthetists and 9.5% (20) nurses participated. Majority believed that use of SSCL improves the safety of procedures, improves communication amongst theatre staff and will result in a reduction in errors in theatre yet there was no commitment for use of SSCL. Although all theatre personnel support implementation and use of SSCL however hierarchical issues, lack of administrative support, lack of training, logistics and timing, high patient volume and overburdened residents, lack of co-ordinator or leadership role and shortage of man power can be impediment to effective use. Nurses and junior doctors play a crucial role. Commitment rather than compliance and teamwork will be the key, ably supported by education and training which should be mandatory for all OT stake holders. Therefore, any measure that can potentially improve patient safety should be embraced and benefits of SSCL be told to motivate them and enhance participation for patient safety. Committed leadership, knowledge sharing and periodic trainings, interdisciplinary communication, feedback and regular audits can define and determine effective implementation process.
Low miR-1231 expression predicts poor prognosis in non-small cell lung cancer and accelerates cell proliferation, migration and invasion
Authors: Zhu Lina , Zhang Chu , Yu Hui , Zhu Lirong 
Published: June 2020

Abstract
Background
MicroRNAs (miRNAs) have been confirmed to be involved in the tumor progression of various cancer types. This study aimed to assess the prognostic significance and biological function of miR-1231 in patients with non-small cell lung cancer (NSCLC).
Methods
The expression of miR-1231 was estimated using quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognosis value of miR-1231 in patients with NSCLC. Cell experiments were performed to assess the biological function of miR-1231 in the tumor progression.
Results
In this study, we found that miR-1231 was an important tumor suppressor with significantly low expression in NSCLC tissues and cell lines compared with normal controls (all P < 0.001). MiR-1231 expression was significantly associated with tumor size (P = 0.037), lymph node metastasis (P = 0.001) and TNM stages (P = 0.001). Furthermore, the patients with low miR-1231 expression had shorter survival time than those with high miR-1231 expression (log-rank P = 0.010). In addition, miR-1231 was found to serve as an independent prognostic biomarker for the patients. The results of cell experiments indicated that miR-1231 downregulation could markedly promote NSCLC cell proliferation, migration and invasion, while miR-1231 overexpression could markedly inhibit NSCLC cell proliferation, migration and invasion.
Conclusion
All the data revealed that a downregulated expression of miR-1231 predicts the poor prognosis of NSCLC and promotes the tumor cell proliferation, migration and invasion. Therefore, we considered that miR-1231 may serve as a therapeutic target for NSCLC treatment.
Relationship between social support status and mortality in a community-based population: a prospective observational study (Yamagata study)
Authors: Uzuki Tsutomu , Konta Tsuneo , Saito Ritsuko , Sho Ri , Osaki Tsukasa , Souri Masayoshi , Watanabe Masafumi , Ishizawa Kenichi , Yamashita Hidetoshi , Ueno Yoshiyuki , Kayama Takamasa 
Published: June 2020

Abstract
Background:Social support, defined as the exchange of support in social relationships, plays a vital role in maintaining healthy behavior and mitigating the effects of stressors. This study investigated whether social support is related to 5-year mortality in health checkup participants.Methods:This study recruited 16,651 subjects (6,797 males, 9,854 females). Social support was evaluated using five component questions: Do you have someone 1) whom you can consult when you are in trouble? 2) whom you can consult when your physical condition is not good? 3) who can help you with daily homework? 4) who can take you to hospital when you don’t feel well? and 5) who can take care of you when you are ill in bed? The association between the component of social support and all-cause and cardiovascular mortality was examined using Cox proportional hazard analysis.Results:The percentage of subjects without social support components was 7.7%-15.0%. They were more likely to be male, non-elderly, and living alone. During the follow-up period, there were 166 all-cause and 38 cardiovascular deaths. Cox proportional analysis adjusted for confounders showed that only the lack of support for transportation to hospital was significantly associated with all-cause (hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.26-3.05) and cardiovascular mortality (HR 3.30, 95% CI 1.41-6.87). These associations were stronger in males than females.Conclusion:This study showed that the lack of social support for transportation to the hospital was independently associated with all-cause and cardiovascular mortality in a community-based population.
Risk Factors and Outcomes of Acute Kidney Injury in Critically Ill Patients With Coronavirus Disease 2019
Authors: Cheng Yichun , Zhang Nanhui , Luo Ran , Zhang Meng , Wang Zhixiang , Dong Lei , Li Junhua , Zeng Rui , Yao Ying , Ge Shuwang , Xu Gang 
Published: June 2020

Abstract
Background: Coronavirus disease 2019 (COVID-19) has emerged as a major global health threat with a great number of deaths worldwide. Acute kidney injury (AKI) is a common complication in patients admitted to the intensive care unit. We aimed toassess the incidence, risk factors and in-hospital outcomes of AKI in COVID-19 patients admitted to intensive care unitMethods: we conducted a retrospective observational study in intensive care unit of Tongji hospital, which was assigned responsibility for the treatments of severe COVID-19 patients by Wuhan government. The AKI was defined and staged based onKidney Disease: Improving Global Outcomes (KDIGO) criteria. Mild AKI was defined as stage 1, and severe AKI was defined as stage 2 or stage 3. We used logistic regression analysis to evaluate AKI risk factors and the association between AKI and in-hospital mortality.Results: A total of 150 patients with COVID-19 were included in our study. The median age of patients was 70 (interquartile range, 60-80) years and 62.7% were male. 70 (46.7%) patients developed AKI during hospitalization, corresponding to the 17.3% in stage 1 and 9.3% in stage 2 and 20.0% in stage 3, respectively. Compared to patients without AKI, patients with AKI had higher proportion of mechanical ventilation mortality and higher in-hospital mortality. 95.5% patients with severe AKI received mechanical ventilation and in-hospital mortality was up to 79.5%. Severe AKI was independently associated with high in-hospital mortality (OR: 4.30; 95% CI: 1.83-10.10). Logistic regression analysis demonstrated that high serum interleukin-6 (OR: 2.54; 95%CI: 1.00-6.42) and interleukin-10 (OR: 3.02; 95%CI: 1.17-7.82) were risk factors for severe AKI development.Conclusions: severe AKI was associated with high in-hospital mortality and inflammatory response may play a role in AKI development in critically ill patients with COVID-19.
Epigenetic Silencing of TET1 Mediated Hydroxymethylation of Base Excision Repair Pathway During Lung Carcinogenesis
Authors: Chen Hong-qiang , Chen Dong-jiao , Li Yan , Yuan Wen-bo , Fan Jun , Zhang Zhe , Han Fei , Jiang Xiao , Chen Jian-ping , Wang Dan-dan , Cao Jia , Liu Jin-yi , Liu Wen-bin 
Published: June 2020

Abstract
Backgroud: The methylcytosine dioxygenase Ten-eleven translocation 1 (TET1) is an important regulator for the balance of DNA methylation and hydroxymethylation through various pathways. Increasing evidence has suggested that TET1 probably involved in DNA methylation and demethylation dysregulation during chemical carcinogenesis. However, the role and mechanism of TET1 during lung cancer remains unclear. Methods: The gene and protein expression were detected by qRT-PCR, Western blot and immunohistochemistry during lung carcinogenesis. Methylation and hydroxymethylation status were evaluated by MeDIP-qPCR and hMeDIP-qPCR. The effect and mechanism of TET1 on lung cancer were identified both in vitro and in vivo models. Results: In this study, we found that TET1 expression was significantly down-regulated and the methylation level was significantly up-regulated in 3-MCA-induced cell malignant transformation model, rat chemical carcinogenesis model, and human lung cancer tissues. Demethylation experiment further confirmed that DNA methylation negatively regulated TET1 gene expression. TET1 overexpression inhibited cell proliferation, migration and invasion in vitro and in vivo, while knockdown of TET1 resulted in an opposite phenotype. DNA hydroxymethylation level in the promoter region of base excision repair (BER) pathway key genes XRCC1, OGG1, APEX1 significantly decreased and the degree of methylation gradually increased in malignant transformed cells. After differential expression of TET1, the level of hydroxymethylation, methylation and expression of these genes also changed significantly. Furthermore, TET1 binds to the promoter of XRCC1, OGG1, and APEX1 to maintain them hydroxymethylated. Blockade of BER pathway key gene alone or in combination significantly diminished the effect of TET1. Conclusions: Our study demonstrated for the first time that TET1 gene expression is regulated by DNA methylation and TET1-mediated hydroxymethylation regulates BER pathway to inhibit the proliferation, migration and invasion during the 3-MCA-induced lung carcinogenesis. These results may suggest that TET1 gene can be used as a potential biomarker and therapy target for lung cancer.