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The use of Corticotropin-releasing factor (CRF) as a marker of agonic stress in abused dogs: Preliminary results

Res Vet Sci. 2021 Sep 28;141:1-3. doi: 10.1016/j.rvsc.2021.09.012. Online ahead of print.

ABSTRACT

In Veterinary Forensic Medicine, determination of the degree of animal suffering is an essential element for the prosecution of perpetrators of animal abuse. The purpose of this study is to find a suitable immunohistochemical marker for the assessment of suffering to be routinely used in Veterinary Forensic Pathology, by analyzing the expression of Corticotropin-releasing factor (CRF) in formalin-fixed brains of dogs as a measurement of the agonic stress. CRF, a key peptide element in exogenous and endogenous stressors adaptation, can regulate endocrine-behavioral responses to stress stimulating pituitary ACTH release and consequent adrenal secretion of glucocorticoids. Since CRF acts in days or weeks, this study investigates its role as a potential distinctive marker between sudden death and death associated with a longer agonic period. The study used immunohistochemistry (IHC) to evaluate the CRF expression in the brain of dogs that suffered sudden death, as compared to dogs that died after long-term agonic stress. IHC labelling analysis was performed with machine-learning-based software and the results were statistically evaluated. Our results demonstrate for the first time that CRF is a promising marker of stress in abused patients also in Veterinary Medicine.

PMID:34634683 | DOI:10.1016/j.rvsc.2021.09.012

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Nevin Manimala Statistics

rMisbeta: A robust missing value imputation approach in transcriptomics and metabolomics data

Comput Biol Med. 2021 Sep 29;138:104911. doi: 10.1016/j.compbiomed.2021.104911. Online ahead of print.

ABSTRACT

Transcriptomics and metabolomics data often contain missing values or outliers due to limitations of the data acquisition techniques. Most of the statistical methods require complete datasets for downstream analysis. A number of methods have been developed for missing value imputation using the classical mean and variance based on maximum likelihood estimators, which are not robust against outliers. Consequently, the performance of these methods deteriorates in the presence of outliers. Hence precise imputation of missing values and outliers handling are both concurrently important. Therefore, in this paper, we developed a robust iterative approach using robust estimators based on the minimum beta divergence method, which simultaneously impute missing values and outliers. We investigate the performance of the proposed method in a comparison with six frequently used missing value imputation methods such as Zero, KNN, robust SVD, EM, random forest (RF) and weighted least square approach (WLSA) through feature selection using both simulated and real datasets. Ten performance indices were used to explore the optimal method such as Frobenius norm (FOBN), accuracy (ACC), sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), detection rate (DR), misclassification error rate (MER), the area under the ROC curve (AUC) and computational runtime. Evaluation based on both simulated and real data suggests the superiority of the proposed method over the other traditional methods in terms of various rates of outliers and missing values. The suggested approach also keeps almost equal performance in absence of outliers with the other methods. The proposed method is accurate, simple, and consumes lower computational time compared to the other methods. Therefore, our recommendation is to apply the proposed procedure for large-scale transcriptomics and metabolomics data analysis. The computational tool has been implemented in an R package, which is publicly available from https://CRAN.R-project.org/package=rMisbeta.

PMID:34634637 | DOI:10.1016/j.compbiomed.2021.104911

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Intranasal as needed naloxone in the treatment of gambling disorder: A randomised controlled trial

Addict Behav. 2021 Sep 30;125:107127. doi: 10.1016/j.addbeh.2021.107127. Online ahead of print.

ABSTRACT

BACKGROUND: Gambling disorder (GD) is a global phenomenon affecting millions of people. GD can result in severe social and financial difficulties and efficacious treatments are warranted. Psychosocial treatments form the basis of treatment. Opioid antagonists (OAs) have however shown promise in previous studies. In a recent imaging study intranasal naloxone was found to rapidly and fully occupy brain μ-opioid receptors. This trial investigates the effect and safety of as needed naloxone in the treatment of gambling disorder.

METHODS: This was a 12-week double blind, randomised control trial comparing intranasal naloxone to placebo. The primary endpoint was gambling urge measured by the Gambling symptom Assessment Scale (G-SAS). Secondary outcome measures were gambling severity measures (PGSI) as well as quality of life (WHO:EUROHIS-8), alcohol consumption (AUDIT), depression (MARDS) and internet use (IDS-9SF). In addition, safety of treatment was assessed. Both treatment groups received psychosocial support.

RESULTS: 126 participants were randomised to treatment groups in a 1:1 ratio. 106 patients completed the study. Gambling urge (GSAS) and other gambling related measured improved in both groups, but no statistically significant difference could be found. Intranasal naloxone was well tolerated, no subjects discontinued the study due to adverse events. No serious adverse drug reactions were observed.

CONCLUSIONS: This study found no difference between the as-needed administration of intranasal naloxone and placebo in reducing gambling urge in persons with GD. Intranasal naloxone was safe and well tolerated.

PMID:34634640 | DOI:10.1016/j.addbeh.2021.107127

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Nevin Manimala Statistics

Comorbidity Prevalence and Impact on Quality of Life in Gay and Bisexual Men Following Prostate Cancer Treatment

Sex Med. 2021 Oct 8;9(6):100439. doi: 10.1016/j.esxm.2021.100439. Online ahead of print.

ABSTRACT

INTRODUCTION: Studies have demonstrated worse health related quality of life (HRQOL) outcomes in gay and bisexual men (GBM) following prostate cancer treatment compared to heterosexual men potentially due to differences in comorbidity burden.

AIM: To establish the prevalence of comorbidities and their association with HRQOL metrics in GBM following prostate cancer treatment.

METHODS: We evaluated HRQOL and prevalence of comorbidities in 193 GBM from the United States and Canada in a cross-sectional, online survey: the Masked for Review. HRQOL was measured with the Expanded Prostate Cancer Index Composite (EPIC) and the 12-Item Short Form Health Survey (SF-12).

MAIN OUTCOME MEASURES: Our outcomes included comorbidity prevalence, mean differences for HRQOL scores by comorbidity status, and mean differences for HRQOL by comorbidity count.

RESULTS: GBM were found to have a higher prevalence of blood vessel disease and mental health disorders but lower prevalence of obesity and type 2 diabetes when compared to published data in general prostate cancer populations. Statistically significant reductions in HRQOL metrics were associated with mental health diagnoses, diabetes, and obesity. Increased number of comorbidities was also associated with reductions in HRQOL metrics in nearly all categories.

CONCLUSION: These results suggest that the worse QOL outcomes in GBM following prostate cancer treatment may be due to differences in comorbidity burden. This study is the first to evaluate the relationship between comorbidities and HRQOL outcomes in GBM. Limitations of this study include a small sample size and cross-sectional study design. If confirmed in larger, longitudinal, clinically confirmed studies, these findings indicate a need to intervene on and consider comorbidities in GBM diagnosed with prostate cancer. Haggart R, Polter E, Ross M, et al. Comorbidity Prevalence and Impact on Quality of Life in Gay and Bisexual Men Following Prostate Cancer Treatment. Sex Med 2021;9:100439.

PMID:34634579 | DOI:10.1016/j.esxm.2021.100439

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Nevin Manimala Statistics

Interleukin 6 predicts increased neural response during face processing in a sample of individuals with schizophrenia and healthy participants: A functional magnetic resonance imaging study

Neuroimage Clin. 2021 Oct 7;32:102851. doi: 10.1016/j.nicl.2021.102851. Online ahead of print.

ABSTRACT

BACKGROUND: Deficits in facial emotion recognition are a core feature of schizophrenia and predictive of functional outcome. Higher plasma levels of the cytokine interleukin 6 (IL-6) have recently been associated with poorer facial emotion recognition in individuals with schizophrenia and healthy participants, but the neural mechanisms affected remain poorly understood.

METHODS: Forty-nine individuals with schizophrenia or schizoaffective disorder and 158 healthy participants were imaged using functional magnetic resonance imaging during a dynamic facial emotion recognition task. Plasma IL-6 was measured from blood samples taken outside the scanner. Multiple regression was used in statistical parametric mapping software to test whether higher plasma IL-6 predicted increased neural response during task performance.

RESULTS: Higher plasma IL-6 predicted increased bilateral medial prefrontal response during neutral face processing compared to angry face processing in the total sample (N = 207, tmax = 5.67) and increased left insula response during angry face processing compared to neutral face processing (N = 207, tmax = 4.40) (p < 0.05, family-wise error corrected across the whole brain at the cluster level).

CONCLUSIONS: These findings suggest that higher peripheral IL-6 levels predict altered neural response within brain regions involved in social cognition and emotion during facial emotion recognition. This is consistent with recent neuroimaging research on IL-6 and suggesting a possible neural mechanism by which this cytokine might affect facial emotion recognition accuracy.

PMID:34634589 | DOI:10.1016/j.nicl.2021.102851

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Natural history of subaortic stenosis in 166 dogs (1999-2011)

J Vet Cardiol. 2021 Sep 2;37:71-80. doi: 10.1016/j.jvc.2021.08.005. Online ahead of print.

ABSTRACT

INTRODUCTION: Subaortic stenosis (SAS) is one of the most common congenital cardiac diseases in dogs. The objective of this study was to provide survival times on a large population of dogs with SAS and to propose a redefined pressure gradient (PG) scale to include a mild, moderate, severe and very severe disease group.

ANIMALS, MATERIALS AND METHODS: Dogs were divided into four groups based on the Doppler-derived PG across the stenosis. Disease severity was defined as follows: mild = PG < 50 mmHg; moderate = PG range 50-80 mmHg; severe = PG range 80-130 mmHg; and very severe = PG > 130 mmHg. Over the study period (1999-2011), 166 client-owned dogs were diagnosed with SAS of which 129 had follow-up information available.

RESULTS: Unadjusted median survival time for severity groups were as follows: mild 10.6 years; moderate 9.9 years; severe 7.3 years; and very severe 3.0 years. Univariable analysis examining the effect of the PG, age at diagnosis and sex found only the PG and age at diagnosis had a significant effect on survival. Adjusted survival curves showed that the survival time in the very severe group was decreased compared with all other groups.

CONCLUSION: Based on the results of this study, a revised SAS classification system with four PG groups is appropriate. Dogs with a PG > 130 mmHg were identified as those with the lowest median survival time.

PMID:34634578 | DOI:10.1016/j.jvc.2021.08.005

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Do closed waste containers lead to less air contamination than opened? A clinical case study at Jena University Hospital, Germany

Waste Manag. 2021 Oct 8;136:11-17. doi: 10.1016/j.wasman.2021.09.031. Online ahead of print.

ABSTRACT

Nosocomial infections are a growing challenge at hospitals. This clinical study aimed to investigate the influence of waste container construction ((open (O), closed (C), and hands-free opening (HF)) on microbial air contamination in a hospital setting. The results are intended to help develop guidelines for waste containers for the collection of non-infectious waste at hospitals and medical facilities. The clinical experiment was conducted at the University Hospital Jena, Germany. Air Impactor samples were performed and microbiologically evaluated for bacteria and fungi both quantitatively and qualitatively. The results were statistically determined using generalized estimating equations. Quantitatively, the lowest bacterial counts in ambient air were found around closed waste containers (114.74 CFU/m3) in comparison to HF (129.28 CFU/m3) and O (126.28 CFU/m3). For fungi, the surrounding air of C (2.08 CFU/m3) and HF (1.97 CFU/m3) waste containers showed a lower impact of fungal air contamination than for O (2.32 CFU/m3). Overall, it was shown that C are more preferable to HF and O waste containers from the point of view of microbial air contamination at hospitals.

PMID:34634566 | DOI:10.1016/j.wasman.2021.09.031

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Comparison of School vs. Home Breakfast Consumption with Cardiometabolic and Dietary Parameters in Low-Income, Multi-Racial/Ethnic Elementary School-Aged Children

J Acad Nutr Diet. 2021 Oct 8:S2212-2672(21)01381-2. doi: 10.1016/j.jand.2021.10.014. Online ahead of print.

ABSTRACT

BACKGROUND: Breakfast consumption is often associated with improving cardiometabolic parameters and diet quality. However, literature evaluating breakfast consumption with these outcomes between the school and home environments is limited.

OBJECTIVE: This study examined relationships between breakfast consumption locations (home versus school) and cardiometabolic parameters, breakfast dietary intake, and daily dietary intake.

DESIGN: This cross-sectional study used baseline data from TX Sprouts, a one-year school-based gardening, nutrition, and cooking cluster-randomized trial, implemented in 16 elementary schools in Austin, TX, in 2016-2019.

PARTICIPANTS/SETTING: Analysis included 383 low-income, multi-racial/ethnic elementary school-aged children (mean age 9.2 years; 60.6% Hispanic; 70.5% free/reduced lunch; 58.5% home breakfast consumers).

MAIN OUTCOME MEASURES: Cardiometabolic parameters were obtained via fasting blood draws, and dietary intake was assessed using one 24-hour dietary recall conducted on a random, unannounced weekday. Cardiometabolic and dietary parameters (i.e., energy intake, macronutrients, and food group servings) for breakfast and for the day were evaluated.

STATISTICAL ANALYSES PERFORMED: Multivariate analysis of covariance was performed to examine cardiometabolic parameters and dietary intake between school and home breakfasts.

RESULTS: School breakfast consumers (SBC) had lower fasting triglyceride levels than home breakfast consumers (HBC) (89.0 mg/dL vs. 95.7 mg/dL; P = 0.03). SBC had lower total fat for the day (P = 0.02) and lower total and saturated fat, sodium, and refined grains at breakfast (P ≤ 0.01) than HBC. However, SBC had lower protein at breakfast (P = 0.01) and higher carbohydrates, total sugar, and added sugar for the day and at breakfast (P ≤ 0.03) than HBC.

CONCLUSION: SBC compared to HBC had lower fat intake, which may have contributed to the lower triglyceride level observed in SBC, but also had lower protein intake at breakfast and higher added sugar intake for the day and at breakfast. These results suggest dietary intake differed between the home and school environments, but more research is needed to evaluate if such differences are due to the School Breakfast Program guidelines.

PMID:34634512 | DOI:10.1016/j.jand.2021.10.014

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Prognostic value of microvessel density in esophageal squamous cell carcinoma-a systematic review and meta-analysis

Pathol Res Pract. 2021 Oct 5;227:153644. doi: 10.1016/j.prp.2021.153644. Online ahead of print.

ABSTRACT

OBJECTIVE: Angiogenesis produced by tumor microenvironment is play an important role in development of esophageal squamous cell carcinoma (ESCC). As a quantitative index of angiogenesis, literature has emerged contradictory results about the prognostic role of microvessel density (MVD) in ESCC. The aim of the study was to explore the impact of the correlation between MVD and the prognosis of ESCC based the published evidence.

METHODS: Pubmed and Web of science database were screened for the relationship of MVD with prognostic feature in ESCC up to March, 2021. 11 relevant articles were used for meta-analysis. The following data were extracted from the literature: author, year, country, the patients number of high/low MVD, tumor-node-metastasis (TNM) classification, clinical stage, lymphoid infiltrates, vessel invasion, invasive depth, differential degree and survival rate. The hazard ratio (HR) and odds ratios (OR) with 95% CI were used to assess the associations between MVD and overall survival (OS). Chi-squared test and I2 statistics were completed to evaluate the heterogeneity in our study. A random-effects model was used when significant heterogeneity existed (I2>50% and p < 0.05). Egger test was used to calculate the publication bias. Subgroup analysis was stratified by antibody, region, sample capacity to explore the source of heterogeneity.

RESULTS: 11 studies with 1055 patients were analyzed. Our results suggested that high MVD is an important factor to advanced TNM classification and clinical stage, and the high MVD is positive correlation with the lymph node invasion and vascular invasion(p < 0.05) in ESCC, but irrelevant to poor differential and invasive depth(p > 0.05). The result also indicated that low MVD is a benefit factor to prolong the survival rate (p < 0.05). And the source of the heterogeneity maybe is that the antibody used to detect the MVD was not consistent, patient number was not large enough and the count method on MVD.

CONCLUSION: Across multiple studies, high MVD is correlated with clinicopathological criteria of poor prognosis and survival in ESCC. MVD could be the quantitative index to reactive angiogenesis and may play a pivotal role in ESCC development and progression. MVD may represent a valuable addition to current pathologic analysis and help to guide prognosis and treatment.

PMID:34634564 | DOI:10.1016/j.prp.2021.153644

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Data augmentation based on waterfall plots to increase value of response data generated by small single arm Phase II trials

Contemp Clin Trials. 2021 Oct 8:106589. doi: 10.1016/j.cct.2021.106589. Online ahead of print.

ABSTRACT

Waterfall plots have been increasingly used to visualize tumor response measurements in Phase II clinical trials. Despite the growing popularity of waterfall plots, quantitative summaries and distribution features of the data indicating antitumor activities are typically not reported. Statistical summaries from the raw and augmented data may provide valuable information for understanding such features. This issue has not been discussed adequately in the literature or fully recognized within the oncology community. In this article, we propose to augment the data using a statistical distribution system. Summary statistics of the data set corresponding to waterfall plot can be calculated using the original sample of the tumor changes or the augmentation sample, which may lead to additional insights into the treatment effect. We demonstrate the proposed method in numerical studies and in a Phase II clinical trial investigating the efficacy of a treatment for ovarian carcinoma. We recommend the proposed statistical analyses for making inferences in addition to the waterfall plot visualization.

PMID:34634476 | DOI:10.1016/j.cct.2021.106589