scholarly journals Big data analysis of mitochondrial DNA substitution models: A regression approach elucidating the effects of codon position and neighboring nucleotides

2018 ◽  
Author(s):  
Keren Levinstein Hallak ◽  
Shay Tzur ◽  
Saharon Rosset
Keyword(s):  
Mitochondrial Dna ◽  
Negative Binomial ◽  
Biological Significance ◽  
Negative Binomial Regression ◽  
Influential Factors ◽  
Codon Composition ◽  
Substitution Mechanism ◽  
Significant Difference ◽  
Dna Substitution ◽  
Neighboring Sites

AbstractWe build on the up-to-date version of Phylotree, a comprehensive and continuously updating phylogeny of global human mtDNA variations (van Oven and Kayser 2009), to better understand the substitution mechanism of the mitochondrial DNA (mtDNA) and its most influential factors. We do so by composing Poisson and negative-binomial regression models relating the rate of occurrence of mtDNA substitutions to various factors. Important factors we identify include the identity of the codon at each position, confirming previous findings about the biological significance of different codons for the same amino acid. Importantly, we also identify a significant effect of neighboring sites. This effect cannot be attributed solely to CpG pairs. A similar effect of neighboring sites was recently described for autosomal DNA substitutions, and we speculate it is related to the basic mutational mechanism itself. Once codon composition and context are taken into account, there is no significant difference in substitution rate between different genes in mtDNA.

scholarly journals Visceral leishmaniasis cyclical trends in Bihar, India – implications for the elimination programme.

2018 ◽  
Vol 2 ◽  
pp. 10 ◽  
Author(s):  
Rinki M Deb ◽  
Michelle C Stanton ◽  
Geraldine M Foster ◽  
Rudra K Das Gupta ◽  
Nupur Roy ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Negative Binomial ◽  
Negative Binomial Regression ◽  
Specific Humidity ◽  
Sand Fly ◽  
Maximum Temperature ◽  
Negative Binomial Regression Model ◽  
Case Detection ◽  
Binomial Regression ◽  
Significant Difference

Background:Visceral leishmaniasis (VL) is a vector-borne disease of public health importance in India, with the highest burden of disease in the states of Bihar, Jharkhand, West Bengal and Uttar Pradesh. The disease is currently targeted for elimination (annual incidence to less than one per 10,000 population) using indoor residual spraying, active case detection and treatment. Historically the disease trend in India has been regarded as cyclical with case resurgence characteristically occurring every 15 years.  Understanding this pattern is essential if the VL elimination gains are to be sustained. To better understand the cyclical trends, annual climatic indicators including rainfall, temperature and humidity over time were compared with annual VL case incidence data. Methods:Annual climate data (rainfall, average and maximum temperature and specific humidity) from 1956-2004 were used to identify potential factors influencing VL incidence.  Months relevant to the VL life-cycle were identified and defined (Monsoon, Sand-fly Peak, Pre-Sand-fly Peak and Annual) for analysis. The Kruskall-Wallis test was used to determine significant difference between categorical rainfall and VL incidence, whilst univariate negative binomial regression models were used to determine predictors of disease incidence.Results:The negative binomial regression model showed statistically significant associations (p <0.05) for VL incidence and maximum temperature, and average temperature, when considering annual and pre-sand fly peak time periods. No other associations between humidity, rainfall or temperature and VL incidence were detected (all values p >0.05). Conclusion:The VL programme in Bihar has made significant progress in adopting best practices for improved treatment and vector control, with the aim to achieve VL elimination.  However, open access granular programme data for indoor residual spray activities and case detection is required to fully understand the role of climate in disease transmission and potential resurgence.

The Use of Sequential Integrated Screening to Stratify Risk in Monochorionic-Diamniotic Twin Pregnancies

2020 ◽  
Author(s):  
Edward Miller ◽  
Cinthia Blat ◽  
Kristen Gosnell ◽  
Juan Gonzalez ◽  
Neda Ghaffari
Keyword(s):  
San Francisco ◽  
Negative Binomial ◽  
Screening Program ◽  
Negative Binomial Regression ◽  
Nuchal Translucency ◽  
Serum Markers ◽  
Second Trimester ◽  
Significant Difference ◽  
The Difference ◽  
Integrated Screening

Objective This study aimed to identify differences in sequential integrated screening and early ultrasound markers in monochorionic/diamniotic (MC/DA) pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) and unequal placental sharing (UPS). Study Design Retrospective cohort study of MC/DA pregnancies evaluated between January 2012 and July 2017 at the University of California San Francisco. MC/DA pregnancies with ultrasound surveillance up to 26 weeks who participated in the California Prenatal Screening Program (CPSP) were included. Pregnancies with structural or genetic anomalies were excluded. UPS was defined as an intertwin growth discordance ≥20%. Intertwin nuchal translucency (NT) discordance was calculated by the absolute value of the difference of the NT of cotwins. Kruskal–Wallis or ANOVA testing was performed where appropriate, and negative binomial regression models were chosen to test for differences in mean biomarker levels by outcome group. Results A total of 191 MC/DA pregnancies were included; 85 were affected by TTTS, 35 by UPS, and 71 controls. Significant differences in intertwin NT discordance in pregnancies complicated by TTTS and UPS compared with controls (p = 0.007) were found. TTTS cases had a mean NT discordance greater than two times that of controls (p = 0.04), while UPS cases had a value more than three times greater (p = 0.003). There was a statistically significant difference in mean second trimester human chorionic gonadotropin (hCG) between the cohorts (p = 0.0002) with TTTS cases having a mean second trimester hCG value 1.5 greater than both controls (p < 0.001) and UPS cases (p = 0.001). Analysis showed a significant difference in mean second trimester inhibin between the three cohorts (p = 0.029). Pregnancies complicated by UPS had a mean second trimester inhibin 1.5 times greater than controls (p = 0.010). Conclusion Our study shows that there are unique differences in early ultrasound and sequential integrated serum markers between MC/DA gestations complicated by TTTS and UPS versus those unaffected. Key Points

scholarly journals An omega-3 Fatty Acid Enriched Diet Reduces Anxiety-like Behavior While High Dietary Sucrose During Chemotherapy Increases Anxiety-like Behavior in Mice (P14-023-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kate Ormiston ◽  
Tonya Orchard ◽  
A Courtney DeVries ◽  
Panchitaa Phuwamongkolwiwat ◽  
Jinhui Li ◽  
...  
Keyword(s):  
Negative Binomial ◽  
Negative Binomial Regression ◽  
Significant Negative Correlation ◽  
Saline Group ◽  
Breast Cancer Patients ◽  
Omega 3 ◽  
Significant Interaction Effect ◽  
Significant Difference ◽  
Underlying Mechanisms ◽  
High Sucrose

Abstract Objectives Incidence of anxiety is nearly three times higher in breast cancer patients compared to healthy women, and chemotherapy may increase risk. Chemotherapy-induced neuroinflammation may contribute to anxiety. Omega-3 fatty acids (n-3 FAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), improve symptoms of anxiety in some studies. However, the effects of n-3 FAs on anxiety during chemotherapy have not been examined. We hypothesized that a diet enriched with n-3 FAs and low in sucrose would significantly improve anxiety-like behavior in chemotherapy treated mice. Methods Female, ovariectomized C57BL/6 mice (7–8 weeks old) were randomly assigned to one of four diets: 2% kcal EPA + DHA or no EPA + DHA with low sucrose or high sucrose. After two and four weeks of diets, mice received a saline or chemotherapy injection (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide), then continued on diets. Seven days after the second injection, mice completed a marble burying test to assess anxiety-like behavior and were sacrificed 10 days later. Significant differences (P < 0.05) were determined using negative binomial regression models. Gene expression of inflammatory cytokines in the hippocampus and cortex was measured using PCR. Spearman correlations assessed associations of cytokines with anxiety. Results Twenty-one % of mice completely buried (i.e., 100% buried) at least one marble; 85% of mice partially buried (>50% but <100% buried) at least one marble. There was a significant n-3 FA effect on number of marbles 100% buried (P = 0.01); fewer marbles were buried by the 2% EPA + DHA group, indicative of less anxiety-like behavior in these mice. There was a significant interaction effect of injection and sucrose on number of marbles 100% buried (P = 0.03); in the chemotherapy group, mice fed low sucrose completely buried fewer marbles than mice fed high sucrose (P < 0.001), but in the saline group, there was no significant difference. There was a significant negative correlation (r = −0.24, P = 0.04) between interleukin-6 in the cortex and number of marbles partially buried. Conclusions Our findings suggest that dietary EPA + DHA reduces, while sucrose and chemotherapy increase, anxiety-like behavior in our mouse model. Future studies should investigate underlying mechanisms. Funding Sources National Cancer Institute.

scholarly journals Comparative effectiveness of dimethyl fumarate in Multiple Sclerosis

2021 ◽  
Author(s):  
Pauline Bosco-Lévy ◽  
Marc Debouverie ◽  
Bruno Brochet ◽  
Francis Guillemin ◽  
Céline Louapre ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Negative Binomial ◽  
Real Life ◽  
Negative Binomial Regression ◽  
Dimethyl Fumarate ◽  
Population Based ◽  
Disability Progression ◽  
Logistic Regression Models ◽  
Significant Difference ◽  
Using Data

Objectives: To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse (ARR) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real life setting. Methods: A population-based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between July 1, 2015 and December 12, 2017, with 4.5 years of database history and 1 to 3.5 years of follow-up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional Propensity Score. Negative binomial regression and a logistic regression models were used to estimate the relative risk (RR ± [95% CI]) of ARR and the Odds Ratio (OR ± [95% CI]) of disability progression, respectively. Results: Overall, 9 304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF- IMM, patients, 1679 DMF-TERI patients, and 376 DMF-FTY patients. DMF significantly reduced ARR compared to IMM (RR 0.72 [0.61 - 0.86]) and TERI (0.81 [0.68 - 0.96]) and did not show any significant difference when compared with FTY The risk of the progression of MS specific disability was not significantly different for any matched cohorts. Interpretation: DMF is associated with lower risk of relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM).

scholarly journals Is area deprivation associated with greater impacts of COVID-19 in care homes across England? A preliminary analysis of COVID-19 outbreaks and deaths

2021 ◽  
pp. jech-2020-215039 ◽  
Author(s):  
Anders Malthe Bach-Mortensen ◽  
Michelle Degli Esposti
Keyword(s):  
Negative Binomial ◽  
Care Home ◽  
Negative Binomial Regression ◽  
Population Characteristics ◽  
Care Homes ◽  
Future Research ◽  
Area Deprivation ◽  
Binomial Regression ◽  
Index Of Multiple Deprivation

IntroductionThe COVID-19 pandemic has disproportionately impacted care homes and vulnerable populations, exacerbating existing health inequalities. However, the role of area deprivation in shaping the impacts of COVID-19 in care homes is poorly understood. We examine whether area deprivation is linked to higher rates of COVID-19 outbreaks and deaths among care home residents across upper tier local authorities in England (n=149).MethodsWe constructed a novel dataset from publicly available data. Using negative binomial regression models, we analysed the associations between area deprivation (Income Deprivation Affecting Older People Index (IDAOPI) and Index of Multiple Deprivation (IMD) extent) as the exposure and COVID-19 outbreaks, COVID-19-related deaths and all-cause deaths among care home residents as three separate outcomes—adjusting for population characteristics (size, age composition, ethnicity).ResultsCOVID-19 outbreaks in care homes did not vary by area deprivation. However, COVID-19-related deaths were more common in the most deprived quartiles of IDAOPI (incidence rate ratio (IRR): 1.23, 95% CI 1.04 to 1.47) and IMD extent (IRR: 1.16, 95% CI 1.00 to 1.34), compared with the least deprived quartiles.DiscussionThese findings suggest that area deprivation is a key risk factor in COVID-19 deaths among care home residents. Future research should look to replicate these results when more complete data become available.

scholarly journals CXCR6-CXCL16 Axis Promotes Breast Cancer by Inducing Oncogenic Signaling

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3568
Author(s):  
Hina Mir ◽  
Neeraj Kapur ◽  
Dominique N. Gales ◽  
Praveen K. Sharma ◽  
Gabriela Oprea-Ilies ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Actin Polymerization ◽  
Biological Significance ◽  
Stage Ii ◽  
Stage Iii ◽  
Soluble Form ◽  
Migration And Invasion ◽  
Antibody Microarray ◽  
Terminal Fragment ◽  
Significant Difference

Precise mechanisms underlying breast cancer (BrCa) metastasis are undefined, which becomes a challenge for effective treatments. Chemokine signaling instigates the trafficking of cancer cells in addition to leukocytes. This study aimed to ascertain the clinical and biological significance of the CXCR6/CXCL16 signaling axis in the pathobiology of BrCa. Our data show a higher expression of CXCR6 in BrCa cell lines and tissues. Stage-III BrCa tissues express significantly higher CXCR6 compared to stage-II tissues. The ligand, CXCL16, could remain tethered to the cell surface, and, after proteolytic shedding of the ectodomain, the N-terminal fragment is released, converting it to its oncogenic, soluble form. Like CXCR6, N-terminal CXCL16 and ADAM-10 were significantly higher in stage-III than stage-II, but no significant difference was observed in the C-terminal fragment of CXCL16. Further, stimulation of the CXCR6/CXCL16 axis activated Src, FAK, ERK1/2, and PI3K signaling pathways, as per antibody microarray analysis, which also underlie CXCL16-induced F-actin polymerization. The CXCR6/CXCL16 axis induces cytoskeleton rearrangement facilitating migration and invasion and supports BrCa cell survival by activating the PI3K/Akt pathway. This study highlights the significance of the CXCR6/CXCL16 axis and ADAM10 as potential therapeutic targets for advanced-stage BrCa.

scholarly journals Association between fatality rate of COVID-19 and selenium deficiency in China

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hai-Yang Zhang ◽  
An-Ran Zhang ◽  
Qing-Bin Lu ◽  
Xiao-Ai Zhang ◽  
Zhi-Jie Zhang ◽  
...  
Keyword(s):  
Negative Binomial ◽  
Viral Infections ◽  
Case Fatality ◽  
Selenium Deficiency ◽  
Negative Binomial Regression ◽  
Negative Binomial Regression Model ◽  
Fatality Rate ◽  
Selenium Content ◽  
Individual Level ◽  
Binomial Regression

Abstract Background COVID-19 has impacted populations around the world, with the fatality rate varying dramatically across countries. Selenium, as one of the important micronutrients implicated in viral infections, was suggested to play roles. Methods An ecological study was performed to assess the association between the COVID-19 related fatality and the selenium content both from crops and topsoil, in China. Results Totally, 14,045 COVID-19 cases were reported from 147 cities during 8 December 2019–13 December 2020 were included. Based on selenium content in crops, the case fatality rates (CFRs) gradually increased from 1.17% in non-selenium-deficient areas, to 1.28% in moderate-selenium-deficient areas, and further to 3.16% in severe-selenium-deficient areas (P = 0.002). Based on selenium content in topsoil, the CFRs gradually increased from 0.76% in non-selenium-deficient areas, to 1.70% in moderate-selenium-deficient areas, and further to 1.85% in severe-selenium-deficient areas (P < 0.001). The zero-inflated negative binomial regression model showed a significantly higher fatality risk in cities with severe-selenium-deficient selenium content in crops than non-selenium-deficient cities, with incidence rate ratio (IRR) of 3.88 (95% CIs: 1.21–12.52), which was further confirmed by regression fitting the association between CFR of COVID-19 and selenium content in topsoil, with the IRR of 2.38 (95% CIs: 1.14–4.98) for moderate-selenium-deficient cities and 3.06 (1.49–6.27) for severe-selenium-deficient cities. Conclusions Regional selenium deficiency might be related to an increased CFR of COVID-19. Future studies are needed to explore the associations between selenium status and disease outcome at individual-level.

Regional Perspective of Safety Performance Functions and Their Application to Florida Intersections in Suburban Residential and Urban General Context Classification Categories

2021 ◽  
pp. 036119812110084
Author(s):  
Ghalia Gamaleldin ◽  
Haitham Al-Deek ◽  
Adrian Sandt ◽  
John McCombs ◽  
Alan El-Urfali
Keyword(s):  
Negative Binomial ◽  
Regression Tree ◽  
Influential Factors ◽  
Safety Performance ◽  
General Context ◽  
Boosted Regression Tree ◽  
Safety Performance Functions ◽  
Traffic Volumes ◽  
Intersection Types ◽  
The Individual

Safety performance functions (SPFs) are essential tools to help agencies predict crashes and understand influential factors. Florida Department of Transportation (FDOT) has implemented a context classification system which classifies intersections into eight context categories rather than the three classifications used in the Highway Safety Manual (HSM). Using this system, regional SPFs could be developed for 32 intersection types (unsignalized and signalized 3-leg and 4-leg for each category) rather than the 10 HSM intersection types. In this paper, eight individual intersection group SPFs were developed for the C3R-Suburban Residential and C4-Urban General categories and compared with full SPFs for these categories. These comparisons illustrate the unique and regional insights that agencies can gain by developing these individual SPFs. Poisson, negative binomial, zero-inflated, and boosted regression tree models were developed for each studied group as appropriate, with the best model selected for each group based on model interpretability and five performance measures. Additionally, a linear regression model was built to predict minor roadway traffic volumes for intersections which were missing these volumes. The full C3R and C4 SPFs contained four and six significant variables, respectively, while the individual intersection group SPFs in these categories contained six and nine variables. Factors such as major median, intersection angle, and FDOT District 7 regional variable were absent from the full SPFs. By developing individual intersection group SPFs with regional factors, agencies can better understand the factors and regional differences which affect crashes in their jurisdictions and identify effective treatments.

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