bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome Analyses on Compound Material Regulating Saline Stress and Alkaline Stress on Cotton
Authors: An Mengjie , Wang Xiaoli , Chang Doudou , Wang Shuai , Hong Dashuang , Fan Hua , Wang Kaiyong
Published: June 2020

Background: Soil salinization and alkalinization are the main factors that affect the agricultural productivity in the world. Evaluating the persistence of the modifier applied in field soils is an important part of the regulation of saline stress and alkaline stress. Result: To determine the molecular mechanism of cotton’s responses to the regulation of saline stress and alkaline stress by the modifier, in this study, cotton was planted in the salinized soil (NaCl 8g kg-1) and alkalized soil (Na2CO3 8g kg-1) after application of the modifier, and ion content, physiological characteristics, and transcription and sequencing of new leaves during the flowering and boll-forming stage of cotton were analyzed. The results showed that compared with saline stress, alkaline stress increased the content of Na+, K+, SOD, and MDA in leaves, and the application of modifier reduced the content of Na+ but increased the K+/Na+ ratio, the activities of SOD, POD, CAT, and REC. Transcriptome analysis revealed that after the application of the modifier, the Na+/H+ exchanger gene in cotton leaves was down-regulated, the K+ transporter, K+ channel and POD genes were up-regulated. Besides, the down-regulation of genes related to lignin synthesis in phenylalanine biosynthesis pathway was consistent with the study results of ion content and physiological characteristics in leaves. The quantitative analysis with PCR proved the reliability of the results of RNA sequencing.Conclusion: These findings indicate that the modifier alleviated saline stress and alkaline stress on cotton by regulating candidate genes in key biological pathways, which improves our understanding of the molecular mechanism of the modifier regulating saline stress and alkaline stress.
SAGA CORE subunit Spt7 is required for correct Ubp8 localization, chromatin association and deubiquitinase activity
Authors: Nuno-Cabanes Carme , Garcia-Molinero Varinia , Martín-Expósito Manuel , Gas Maria-Eugenia , Oliete-Calvo Paula , Garcia-Oliver Encar , Iglesia-Vaya María De la , Rodriguez-Navarro Susana
Published: June 2020

BackgroundHistone H2B deubiquitination is performed by numerous deubiquitinases in eukaryotic cells including Ubp8, the catalytic subunit of the tetrameric deubiquitination module (DUBm: Ubp8; Sus11; Sgf11; Sgf73) of the Spt-Ada- Gcn5 acetyltransferase (SAGA). Ubp8 is linked to the rest of SAGA through Sgf73 and is activated by the adaptors Sus1 and Sgf11. It is unknown if DUBm/Ubp8 might also work in a SAGA-independent manner.ResultsHere we report that a tetrameric DUBm is assembled independently of the SAGA-core components SPT7, ADA1 and SPT20. In the absence of SPT7, i.e. independent of the SAGA complex, Ubp8 and Sus1 are poorly recruited to SAGA-dependent genes and to chromatin. Notably, cells lacking Spt7 or Ada1, but not Spt20, show lower levels of nuclear Ubp8 than wild type cells, suggesting a possible role for SAGA CORE subunits in Ubp8 localization. Last, deletion of SPT7 leads to defects in Ubp8 deubiquitinase activity in in vivo and in vitro assays.ConclusionsCollectively, our studies show that a stable DUBm is assembled regardless of SAGA integrity; however its function and localization is affected by the absence of Spt7 or Ada1.
Regulator of Cullins-1 (ROC1) Negatively Regulates the Gli2 Regulator SUFU to Activate the Hedgehog Pathway in Bladder Cancer
Authors: Wang Wei , Qiu Jianxin , Qu Pin , Chen Hui , Lan Jianyun , Chen Haitao , Li Lei , Gu Min
Published: June 2020

Background: The regulator of cullins-1 (ROC1) is an essential subunit in the Cullin-RING ligase (CRL) protein complex and was shown to be critical in bladder cancer cell survival and malignant progression. This study aimed to explore the regulatory mechanism of ROC1 in bladder cancer malignant progression. Methods: This study explored the underlying mechanisms using both in vitro and in vivo experiments. The expression of the components of Sonic Hedgehog (SHH) pathway was determined by western blotting analysis. ROC1 expression in human tumours was evaluated by immunohistochemical analysis. Results: The data showed that ROC1 overexpression promoted growth of bladder cancer cells, whereas knockdown of ROC1 expression had an opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target SUFU for ubiquitin-dependent degradation, allowing the Gli2 release from the SUFU complex to activate SHH pathway. Furthermore, knockdown of SUFU expression partially rescue the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. At ex vivo, tissue microarray analysis of human bladder cancer specimens revealed an positive association of ROC1 expression with the SHH pathway activity. Conclusion: The current study demonstrated the dysregulation of ROC1-SUFU-GLI2 axis played an important role in bladder cancer progression and targeting of ROC1 expression is warranted further investigation as a novel strategy for future control of bladder cancer.
The Effect of Different Levels of Prostate-Specific Antigen and Prostate Imaging Report and Data System Scores on Logistic Regression Model to Predict Clinically Significant Prostate Cancer—A Single Center Retrospective Study
Authors: Zhang Loudong , Zhu Hua , Gu Donghua , Pan Xiaodong , zheng bing
Published: June 2020

Background: At present, there are various clinical regression models for predicting prostate cancer. But what about the diagnostic effectiveness of these models in different parameter ranges, and are the models applicable to everyone? This study aimed to study the influence of different levels of prostate-specific antigen (PSA) and Prostate Imaging Report and Data System version 2 (PI-RADS v2) scores on the regression model to predict clinically significant prostate cancer (csPCa).Methods: This retrospective study screened 251 patients from our hospital, who were divided into different groups. The regression model was established for each group to predict csPCa, and the effects of PSA and PI-RADS scores on each model were analyzed through the diagnostic effects of the model.Results: In patients with lower PSA scores, although the model was less sensitive than PSA, the AUC of the model was much greater. With the rise of PSA, the sensitivity of the model surpassed that of PSA, while the specificity became the opposite, and the AUC gap also gradually decreased. In the group with low PI-RADS score, the sensitivity and specificity of PI-RADS were lower than the model, and the gap was larger. Although the gap between the two gradually decreased with the increase of PI-RADS, the diagnostic efficiency of the model was still slightly larger than that of pure PI-RADS.Conclusion: As the PSA and PI-RADS v2 scores increase, the diagnostic advantages of the regression model will gradually decrease. However, for patients with low levels of PSA and PI-RADS scores,the regression model is less affected by PSA and PI-RADS, and can better utilize its clinical diagnostic advantages.
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

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

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

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

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

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

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

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

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

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

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

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.
Spatial Patterns and Associated Factors of HIV Seropositivity among Adults in Ethiopia from EDHS 2016: A Spatial and multilevel analysis
Authors: Hailu Bayuh Asmamaw , Tadese Fentaw , Bogale Getahun Gebre , Molla Asressie , Miheretu Birhan Asmame , Beyene Joseph
Published: June 2020

BackgroundHIV is a major public health problem, especially in developing countries including Ethiopia. Exploring the spatial pattern, distribution and associated factors of HIV Seropositivity is important to monitor, and design effective intervention programs. Therefore, this study showed associated factors and spatial variation of HIV Seropositivity in Ethiopia.MethodThis secondary data analysis, sampling technique and procedures were done by Ethiopipan Central Statistical Agency. A total sample of 25,774 individuals data were extracted from the 2016 EDHS data mainly HIV biomarkers, IR, MR, and GPS. Spatial heterogeneity analysis were done using tools like Morans I, Local G*, Interpolation, and Kulldorff’s scan statistic. The spatial analysis was carried out by using open source software (QGIS, GeoDa, SaTScan). Multilevel logistic regression analysis was used to identify both individual and household level factors associated with HIV Seropositivity and the analysis was carried out by Stata 14. Finally AOR with 95% confidence interval of mixed-effect logistic regression result in the full model was used to report.ResultThe prevalence of HIV/AIDS was found 0.93% at the national level. The highest prevalence regions were Gambela, Addis Ababa, Harari, and Dire Dawa, which accounts for 4.79%, 3.36%, 2.65%, and 2.6%, respectively. Similarly, the most likely high-risk HIV Seropositivity spatial cluster was found in the Gambela region and Addis Ababa followed by Harari and Diredawa. In a multilevel analysis at the individual level being married [AOR = 2.19 95%CI: (1.11, 4.31)] and previously married [AOR = 6.45, 95%CI (3.06, 13.59)] were significantly associated with serropositivity. Regarding household level place of residence [urban: AOR = 6.13 CI: (3.12, 12.06)] were associated with HIV Seropositivity.ConclusionThe distribution of HIV cases was not random. High cluster HIV cases were found in Gambela, Addis Abeba, Harari, and Dire Dawa. At the individual level, some characters are high risk like being previously married, start sex at a younger age, female household headed, urban residence, and lower household size is more affected by HIV/AIDS. So any concerned bodywork around this risk group and area can be effective in the reduction of transmission.
­­­grapevine (Vitis Spp.) Rootstock Stilbenoid Associations With Host Resistance to and Induction by Root Knot Nematodes, Meloidogyne Incognita
Authors: Wallis Christopher
Published: June 2020

Objective:The root knot nematodes (RKN)Meloidogyne incognita can severely reduce grapevine yields over time. Grapevine rootstocks have been developed from wild Vitis species that provide resistance to nematode infections. However, the potential biochemical or mechanical mechanisms of resistance have not been thoroughly explored. Therefore, this study measured levels of stilbenoids in roots of non-infected and RKN-infected grapevines with Cabernet Sauvignon scion grafted to susceptible (O39-16) or resistant (Freedom) rootstocks. This was part of a larger effort to assess phenolic compound levels within grapevine rootstocks to determine roles of stilbenoidcompounds in improving nematode resistance and overall plant health.Results: None of the assessed compounds were consistently greater in RKN infected plants versus healthy controls. Stilbenoids putatively identified as pallidol, ɑ-viniferin, miyabenol C, and hopeaphenol were overall much greater in Freedom than O39-16 rootstocks. By contrast, the stilbenoids ampelopsin A, ω-viniferin, and vitisin B were greater in O39-16 than Freedom. O39-16 and Freedom had similar levels of other stilbenoids especially monomers and dimers. Potentially the greater levels of specific stilbenoids present in Freedom than O39-16 provided RKN resistance. If validated, breeding programs could utilize the increased presence of these compounds as a marker for increased resistance to nematodes.
Assessment of Tuberous Sclerosis-Associated Neuropsychiatric Disorders Using the MINI-KID tool: A Pediatric Cohort Study
Authors: Ding Yifeng , Wang Ji , Zhou Hao , Li Taoli , Zhou Shuizhen , Wang Yi
Published: June 2020

Background: The tuberous sclerosis-associated neuropsychiatric disorders (TAND) has not been studied before in China. We aimed to assess TAND using the Mini International Neuropsychiatric Interview for Children (MINI-KID) in China.Results: A total of 81.05% of patients (77/95) had at least one TAND, and 70.53% (67/95) had an intellectual disability. The MINI-KID tool diagnosed a total of 15 neuropsychiatric diseases, the most common of which were attention-deficit/hyperactivity disorder (ADHD) (51.58%, 49/95) and social anxiety disorder (41.05%, 39/95). The number of children with neuropsychiatric diseases in the TSC group was significantly greater than the numbers in the normal development group (P <0.0001). Epilepsy before the age of 2 years, an epilepsy duration exceeding 2 years, a seizure frequency of more than once a month, and use of more than 2 antiepileptic drugs were closely associated the occurrence of TAND.Conclusion: The MINI-KID can be used for the screening and diagnosis of TAND in children with TSC aged 6-16 years. The incidence of neuropsychiatric diseases in children with TSC can arrive at 81.05%. Early onset of epilepsy, long duration of epilepsy, frequent seizures, and refractory epilepsy are risk factors for TAND. Early, reasonable, and rapid control of seizures may reduce the risk of neuropsychiatric illness in children with epilepsy.
CFHR5 Genetic Variations and Serum Levels in Patients with Immune-Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy
Authors: Garam Nóra , Cserhalmi Marcell , Prohászka Zoltán , Szilágyi Ágnes , Veszeli Nóra , Szabó Edina , Uzonyi Barbara , Iliás Attila , Aigner Christof , Schmidt Alice , Gaggl Martina , Sunder-Plassmann Gere , Bajcsi Dóra , Brunner Jürgen , Dumfarth Alexandra , Cejka Daniel , Flaschberger Stefan , Flögelova Hana , Haris Ágnes , Hartmann Ágnes , Heilos Andreas , Mueller Thomas , Rusai Krisztina , Arbeiter Klaus , Hofer Johannes , Jakab Dániel , Sinkó Mária , Szigeti Erika , Bereczki Csaba , Janko Viktor , Kelen Kata , Reusz György S. , Szabó Attila J. , Klenk Nóra , Kóbor Krisztina , Kojc Nika , Knechtelsdorfer Maarten , Laganovic Mario , Lungu Adrian Catalin , Meglic Anamarija , Rus Rina , Kersnik-Levart Tanja , Macioniene Ernesta , Miglinas Marius , Pawłowska Anna , Stompór Tomasz , Podracka Ludmila , Rudnicki Michael , Mayer Gert , Rysava Romana , Reiterova Jana , Saraga Marijan , Seeman Tomáš , Zieg Jakub , Sládková Eva , Stajic Natasa , Szabó Tamás , Capitanescu Andrei , Stancu Simona , Tisljar Miroslav , Galesic Kresimir , Tislér András , Vainumäe Inga , Windpessl Martin , Zaoral Tomas , Zlatanova Galia , Józsi Mihály , Csuka Dorottya
Published: June 2020

Background: Factor H-related-5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement and follow-up data.Results: 120 patients with a histologically-proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger-sequencing, and selected mutants were studied as recombinant proteins in ELISA and SPR.Eight relevant CFHR5 variations in 14 patients (11.7%) were observed, 5 of them identified as pathogenic for C3G. The FHR-5G278S and FHR-5R356H mutations altered the interaction of FHR-5 with C3b, when compared to the FHR-5WT. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period, furthermore, it showed clear association with signs of hypocomplementemia and clinically meaningful clusters.Conclusions: Our observations support the hypothesis that FHR-5 protein and its genetic alterations play a role in the pathogenesis of IC-MPGN/C3G.
Inflammation Cytokine Expression and Association With Clinical Outcomes in Critically Ill Patients After Major Surgery: A Retrospective Cohort Study
Authors: Yan Yamin , Wang Xiaorong , Hu Yan , Yu Zhenghong , Tang Yingjia , Li Jingjing , Mei Jinghua , Pan Wenyan , Zhang Yuxia
Published: June 2020

Background The associations of serum cytokine levels and critically ill patient outcomes after major surgery remain unclear. The use of cytokine markers to predict outcomes in critically ill patients is controversial.Objective To determine the levels of IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α and procalcitonin in critical surgical ICU(SICU) patients and evaluate their associations with patient outcome and clinical significance.Methods This was a retrospective cohort study of consecutive patients admitted to the SICU in Zhongshan Hospital, Fudan University. The program ran from January 1, 2018, to June 30, 2019. The levels of IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α and procalcitonin were detected, and their relationship with patient outcomes was investigated.The primary outcome was in-hospital mortality, compared by a multivariable logistic regression analysis among the survivors and nonsurvivors.Results Overall, 5,257 patients were included in this study for their first SICU admission; 5,099 patients survived, 158 patients died, and the mortality rate was 3.0%(158/5,257). Univariate and multivariate analyses showed that nonsurvivors had increased levels of IL-1(OR=1.855, P=0.000) and IL-2(OR=1.51, P=0.000) compared with survivors. In addition, 196 patients(3.7%) were readmitted to the SICU, and data from 187 patients were collected. Of these, 161 patients survived, and 26 patients died; the mortality rate was 13.9%(26/187), which was much higher than that of the first round of patients. The level of IL-2 significantly influenced SICU readmission(OR=3.921, P=0.000).For the third round of SICU admission, 10 patients were included, 7 patients survived, and 3 patients died; the mortality rate was 30.0%(3/10). Furthermore, older age, longer time of SICU stay, and higher rate of mechanical ventilation and CRRT were associated with patient death.Conclusions High levels of cytokines may be risk factors for mortality and SICU readmission in critically ill patients who receive major surgery. Further work is still needed to determine which unmeasured characteristics and therapies may contribute to the increased risk observed.
Integrating GWAS, linkage mapping and gene expression analyses reveals the genetic control of growth period traits in rapeseed (Brassica napus L.)
Authors: wang tengyue , Wei Lijuan , wang Jia , Xie Ling , Li Yangyang , Ran Shuyao , Ren Lanyang , Lu Kun , Li Jiana , Timko Michael P. , Liu Liezhao
Published: June 2020

Background: Brassica napus is one of the most important oilseed crops, and also an important biofuel plant due to its low air pollution and renewability. Growth period are important traits that affect yield and are crucial for its adaptation to different environments in B. napus.Results: To elucidate the genetic basis of growth period traits, genome-wide association analysis (GWAS) and linkage mapping were employed to detect the quantitative trait loci (QTL) for days to initial flowering (DIF), days to final flowering (DFF), days from initial flowering to final flowering (FP), days from final flowering to maturity (MT), and whole growth period (GP). A total of 146 SNPs were identified by association mapping, and 83 QTLs were identified by linkage mapping using the RIL population. Among these QTLs, 19 were pleiotropic SNPs related to multiple traits, and six (q18DFF.A03-2, q18MT.A03-2, q17DFF.A05-1, q18FP.C04, q17DIF.C05 and q17GP.C09) were consistently detected using both mapping methods. Additionally, we performed RNA sequencing to analyze the differential expression of gene (DEG) transcripts between early- and late-flowering lines selected from the RIL population, and the DEGs were integrated with association mapping and linkage analysis to confirm their roles in the growth period. Consequently, twelve candidate genes associated with growth period traits were identified in B. napus. Among these genes, seven have polymorphic sites in the coding sequence and the upstream 2-kb sequence based on the resequencing data. The haplotype BnaSOC1.A05-Haplb and BnaLNK2.C06-Hapla showed more favorable phenotypic traits. Conclusions: The candidate genes identified in this study will contribute to our genetic understanding of growth period traits and can be used as targets for target mutations or marker assisted breeding for rapeseed adapted to different environments.
Short term outcomes of newborn infants with Hypoxic Ischaemic Encephalopathy treated with therapeutic hypothermia in a low resource setting: A retrospective cohort study
Authors: DAMOI JENNIFER KRICITOBER , Sebunya Robert , Kirabira Victoria Nakibuuka
Published: June 2020

Background

Hypoxic Ischemic Encephalopathy (HIE) remains a significant cause of death and neuro-developmental deficits among children, especially in resource limited settings. Therapeutic hypothermia which is the mainstay of treatment for moderate to severe hypoxic ischaemic encephalopathy in developed countries, is not widely practiced in low resource settings and the available data is limited. We aimed to determine the short term outcomes and factors associated with survival among newborn infants with moderate to severe hypoxic ischaemic encephalopathy treated with therapeutic hypothermia at St. Francis Hospital, Nsambya.
Methods

Retrospective cohort study of 81 newborn infants with moderate to severe HIE who were 36 weeks and above that were cooled from June 2016 to February 2019, at St. Francis Hospital, Nsambya, Kampala, Uganda. Data on maternal and infant characteristics, clinical outcomes were extracted from the HIE registry and HIE follow up forms. Descriptive analysis was done to get the patient characteristics. Survival analysis was done to compare outcome among the groups of infants with significant factors at bivariate analysis. Multiple cox proportional hazards regression analysis was done to determine the factors independently associated with survival.
Results

The proportion of newborn infants who survived was 68/81(84%), (95%: CI: 0.74, 0.91).The factors associated with survival were a Thompson score of 7 to10 at initiation of cooling(HR: 0.07, 95% CI: 0.01, 0.94) and at 24 hours of cooling(HR:0.03, 95%CI: 0.004, 0.21), being born within the hospital providing therapeutic hypothermia (HR: 0.26, 95% CI: 0.07, 0.94) and not needing mechanical ventilator (HR: 0.03, 95% CI: 0.01, 0.14) or inotropic support.(HR: 0.13, 95%CI: 0.04, 0.38). The median time to attainment of full cup feeds was 6 days, with the majority 43/68(63%) attaining full feeds from 5 to 8 days. The median time to discharge was 7 days, and the median time to death was 3 days. The median Thompson score at discharge was 1 and at death was 16
Conclusion

The survival rate of cooled infants in our setting at 84% is comparably high. The majority of infants have normal neurology at discharge.