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Background The Visiopharm human epidermal growth factor receptor 2 (HER2) digital imaging analysis (DIA) algorithm assesses digitized HER2 immunohistochemistry (IHC) by measuring cell membrane connectivity. We aimed to validate this algorithm for clinical use by comparing with pathologists' scoring and correlating with HER2 fluorescence in situ hybridization (FISH) results. Materials and Methods The study cohort consisted of 612 consecutive invasive breast carcinoma specimens including 395 biopsies and 217 resections. HER2 IHC slides were scanned using Philips IntelliSite Scanners, and the digital images were analyzed using Visiopharm HER2-CONNECT App to obtain the connectivity values (0-1) and scores (0, 1+, 2+, and 3+). HER2 DIA scores were compared with Pathologists' manual scores, and HER2 connectivity values were correlated with HER2 FISH results. Results The concordance between HER2 DIA scores and pathologists' scores was 87.3% (534/612). All discordant cases (n = 78) were only one-step discordant (negative to equivocal, equivocal to positive, or vice versa). Five cases (0.8%) showed discordant HER2 IHC DIA and HER2 FISH results, but all these cases had relatively low HER2 copy numbers (between 4 and 6). HER2 IHC connectivity showed significantly better correlation with HER2 copy number than HER2/CEP17 ratio. Conclusions HER2 IHC DIA demonstrates excellent concordance with pathologists' scores and accurately discriminates between HER2 FISH positive and negative cases. HER2 IHC connectivity has better correlation with HER2 copy number than HER2/CEP17 ratio, suggesting HER2 copy number may be more important in predicting HER2 protein expression, and response to anti-HER2-targeted therapy. Copyright © 2020 Journal of Pathology Informatics.Diabetes or diabetes mellitus is a complex or polygenic disorder, which is characterized by increased levels of glucose (hyperglycemia) and deficiency in insulin secretion or resistance to insulin over an elongated period in the liver and peripheral tissues. Thiazolidine-2,4-dione (TZD) is a privileged scaffold and an outstanding heterocyclic moiety in the field of drug discovery, which provides various opportunities in exploring this moiety as an antidiabetic agent. In the past few years, various novel synthetic approaches had been undertaken to synthesize different derivatives to explore them as more potent antidiabetic agents with devoid of side effects (i.e., edema, weight gain, and bladder cancer) of clinically used TZD (pioglitazone and rosiglitazone). In this review, an effort has been made to summarize the up to date research work of various synthetic strategies for TZD derivatives as well as their biological significance and clinical studies of TZDs in combination with other category as antidiabetic agents. This review also highlights the structure-activity relationships and the molecular docking studies to convey the interaction of various synthesized novel derivatives with its receptor site. © 2020 THE AUTHORS. Published by Elsevier BV on behalf of Cairo University.Unlike many other water disinfection methods, hydroxyl radicals (HO•) produced by the Fenton reaction (Fe2+/H2O2) can inactivate pathogens regardless of taxonomic identity of genetic potential and do not generate halogenated disinfection by-products. Hydrogen peroxide (H2O2) required for the process is typically electrogenerated using various carbonaceous materials as cathodes. However, high costs and necessary modifications to the cathodes still present a challenge to large-scale implementation. In this work, we use granular activated carbon (GAC) as a cathode to generate H2O2 for water disinfection through the electro-Fenton process. GAC is a low-cost amorphous carbon with abundant oxygen- and carbon-containing groups that are favored for oxygen reduction into H2O2. Results indicate that H2O2 production at the GAC cathode is higher with more GAC, lower pH, and smaller reactor volume. Through the addition of iron ions, the electrogenerated H2O2 is transformed into HO• that efficiently inactivated model pathogen (Escherichia coli) under various water chemistry conditions. Chick-Watson modeling results further showed the strong lethality of produced HO• from the electro-Fenton process. This inactivation coupled with high H2O2 yield, excellent reusability, and relatively low cost of GAC proves that GAC is a promising cathodic material for large-scale water disinfection.Introduction The growing use of Geographic Information Systems (GIS) to link population-level data to health facility data is key for the inclusion of health system environments in analyses of health disparities. However, such approaches commonly focus on just a couple of aspects of the health system environment and only report on the average and independent effect of each dimension. Methods Using GIS to link Demographic and Health Survey data on births (2008-13/14) to Service Availability and Readiness Assessment data on health facilities (2010) in Zambia, this paper rigorously measures the multiple dimensions of an accessible health system environment. Using multilevel Bayesian methods (multilevel analysis of individual heterogeneity and discriminatory accuracy), it investigates whether multidimensional health system environments defined with reference to both geographic and social location cut across individual-level and community-level heterogeneity to reliably predict facility delivery. Results Random in)) 2020. Re-use permitted under CC BY. Published by BMJ.Visualising maternal and newborn health (MNH) outcomes at fine spatial resolutions is crucial to ensuring the most vulnerable women and children are not left behind in improving health. Disaggregated data on life-saving MNH interventions remain difficult to obtain, however, necessitating the use of Bayesian geostatistical models to map outcomes at small geographical areas. While these methods have improved model parameter estimates and precision among spatially correlated health outcomes and allowed for the quantification of uncertainty, few studies have examined the trade-off between higher spatial resolution modelling and how associated uncertainty propagates. Here, we explored the trade-off between model outcomes and associated uncertainty at increasing spatial resolutions by quantifying the posterior distribution of delivery via caesarean section (c-section) in Tanzania. Overall, in modelling delivery via c-section at multiple spatial resolutions, we demonstrated poverty to be negatively correlated across spatial resolutions, suggesting important disparities in obtaining life-saving obstetric surgery persist across sociodemographic factors. Lastly, we found that while uncertainty increased with higher spatial resolution input, model precision was best approximated at the highest spatial resolution, suggesting an important policy trade-off between identifying concealed spatial heterogeneities in health indicators. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.Objectives Skilled birth attendance is the single most important intervention to reduce maternal mortality. However, studies have not used routinely collected health service birth data at named health facilities to understand the influence of distance and quality of care on childbirth service utilisation. Thus, this paper aims to quantify the influence of distance and quality of healthcare on utilisation of birthing services using routine health data in Eastern Region, Ghana. Methods We used a spatial interaction model (a model that predicts movement from one place to another) drawing on routine birth data, emergency obstetric care surveys, gridded estimates of number of pregnancies and health facility location. We compared travel distances by sociodemographic characteristics and mapped movement patterns. Results A kilometre increase in distance significantly reduced the prevalence rate of the number of women giving birth in health facilities by 6.7%. Although quality care increased the number of women giving birth in health facilities, its association was insignificant. Women travelled further than expected to give birth at facilities, on average journeying 4.7 km beyond the nearest facility with a recorded birth. Women in rural areas travelled 4 km more than urban women to reach a hospital. We also observed that 56% of women bypassed the nearest hospital to their community. Conclusion This analysis provides substantial opportunities for health planners and managers to understand further patterns of skilled birth service utilisation, and demonstrates the value of routine health data. Also, it provides evidence-based information for improving maternal health service provision by targeting specific communities and health facilities. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.Mitochondrial DNA (mtDNA) is a circular genome of 16 kb that is present in multiple copies in mitochondria. mtDNA codes for genes that contribute to mitochondrial structure and function. A long-standing question has asked whether mtDNA is epigenetically regulated similarly to the nuclear genome. Recently published data suggest that unlike the nuclear genome where CpG methylation is the norm, mtDNA is methylated predominantly at non-CpG cytosines. This raises important methodological considerations for future investigations. In particular, existing bisulphite PCR techniques may be unsuitable due to primers being biased towards amplification from unmethylated mtDNA. Here, we describe how this may have led to previous studies underestimating the level of mtDNA methylation and reiterate methodological strategies for its accurate assessment. selleck chemicals llc © The Author(s) 2020. Published by Oxford University Press.Background Our recent study has revealed that many hospitalized patients with acquired long QT syndrome (ALQTS) are cancer patients. This study aims to determine the risk factors and outcomes of hospitalized cancer patients with ALQTS. Methods We performed a matched case-control study within a cohort of 10,180 cancer patients hospitalized between September 2013 and April 2016. Among them, 150 patients defined as having severe ALQTS with a markedly prolonged QT interval (QTc ≥ 500 ms) were compared with 293 age-, sex- and cancer-type-matched controls (non-ALQTS). Death as the endpoint was followed for up to 2 years. Cox regression and Kaplan-Meier survival analyses were performed to assess the effects of particular clinical variables on all-cause mortality. Multivariate logistic regression was performed to calculate odds ratios (OR) for various predictors of QT prolongation. Results The mortality was significantly higher in ALQTS group (63.3% vs. 33.4%). Hypertension, hypokalemia, hypocalcemia, QT-prolonging drugs, infection, anemia, anti-microtubule agents were contributing factors to ALQTS. Renal insufficiency, male gender and hypokalemia were found to be independent risk factors for all-cause mortality in ALQTS group. Conclusion Markedly prolonged QT interval was seen in 1.5% of hospitalized cancer patients. The all-cause mortality was high in cancer patients with severe ALQTS. © The Author(s). 2020.
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