The In Vivo Transcriptomic Blueprint of Mycobacterium tuberculosis in the Lung

Mycobacterium tuberculosis (Mtb) genes encoding proteins targeted by vaccines and drugs should be expressed in the lung, the main organ affected by Mtb, for these to be effective. However, the pulmonary expression of most Mtb genes and their proteins remains poorly characterized. The aim of this study is to fill this knowledge gap. We analyzed large scale transcriptomic datasets from specimens of Mtb-infected humans, TB-hypersusceptible (C3H/FeJ) and TB-resistant (C57BL/6J) mice and compared data to in vitro cultured Mtb gene-expression profiles. Results revealed high concordance in the most abundantly in vivo expressed genes between pulmonary Mtb transcriptomes from different datasets and different species. As expected, this contrasted with a lower correlation found with the highest expressed Mtb genes from in vitro datasets. Among the most consistently and highly in vivo expressed genes, 35 have not yet been explored as targets for vaccination or treatment. More than half of these genes are involved in protein synthesis or metabolic pathways. This first lung-oriented multi-study analysis of the in vivo expressed Mtb-transcriptome provides essential data that considerably increase our understanding of pulmonary TB infection biology, and identifies novel molecules for target-based TB-vaccine and drug development.

Indicators for Sanitation Quality in Low-Income Urban Settlements: Evidence from Kenya, Ghana, and Bangladesh

In recent years, shared facilities have contributed substantially to increased access to sanitation in urban areas. While shared sanitation is often the only viable option in densely-populated, low-income urban areas, it is currently considered a “limited" solution by the international community. In this paper, we analyze the conditions under which shared sanitation could be considered of adequate quality and propose a set of indicators associated with sanitation quality to be included in national household surveys. We conducted a survey with 3600 households and 2026 observational spot-checks of shared and individual household toilets in Kisumu (Kenya), Kumasi (Ghana), and Dhaka (Bangladesh). We develop a composite sanitation quality outcome measure based on observational data. Using regression analysis, we identify self-reported indicators that correlate with the spot-checked composite measure and are, therefore, robust with regard to reporting bias. Results show that (pour-) flush toilets are a highly informative indicator for sanitation quality compared to other toilet technologies. In contrast to previous arguments and depending on the context, sharing a toilet has a comparatively lower correlation with sanitation quality. Toilets still show good quality if shared among only 2–3 households. Toilet location and lighting, as well as the presence of a lockable door, are equally strong indicators for sanitation quality and could serve as alternative indicators. The findings suggest that the sanitation service levels defined by the WHO and UNICEF might be reconsidered to better capture the quality of sanitation facilities in low-income urban settlements.

Benchmarking computational methods to calculate the octanol/water partition coefficients of a diverse set of organic molecules

In the discovery process of new drugs and the development of novel therapies in medicine, computational modeling is a complementary tool for the design of new molecules by predicting for example their solubility in different solvents. Here, we benchmarked several computational methods to calculate the partition coefficients of a diverse set of 161 organic molecules with experimental logP values obtained from the literature. In general, density functional theory methods yielded the best correlations and lower average deviations. Although results are obtained faster with semiempirical and molecular mechanics methodologies, these methods yielded higher average deviations and lower correlation coefficients than hybrid density functional theory methods. We recommend the use of an empirical formula to correct the calculated values with each methodology tested.

Validity and Reliability of a Phone App and Stopwatch for the Measurement of 505 Change of Direction Performance: A Test-Retest Study Design

Purpose: The aim of this study was to explore the validity and reliability of a phone app [named: change of direction (COD) timer] and stopwatches for the measurement of COD performance.Methods: Sixty-two youth basketball players (age: 15.9±1.4yrs., height: 178.8±11.0cm, and body mass: 70.0±14.1kg) performed six trials of 505 COD test (with the left side being the plant leg first, then the right side). The completion time was measured simultaneously via timing gates (with error correction processing algorithms), the phone app, and stopwatches.Results: There was an almost perfect correlation and agreement between timing gates and COD timer (r=0.978; SEE=0.035s; and LoA=−0.08~0.06s), but a lower correlation and agreement between timing gates and stopwatch (r=0.954; SEE=0.050s; and LoA=−0.17~0.04s) with statistical significance in completion time (ES=1.29, 95%CI: 1.15–1.43, p<0.01). The coefficient of variation revealed similar level of dispersion between the three timing devices (timing gates: 6.58%; COD timer: 6.32%; and stopwatch: 6.71%). Inter-observer reliability (ICC=0.991) and test-retest reliability (ICC=0.998) were excellent in COD timer, while the inter-observer reliability was lower (ICC=0.890) in the stopwatches.Conclusion: In the 505 COD test, the COD timer was able to provide a valid and reliable measurement. On the contrary, stopwatch was not recommended because of large error. Thus, if timing gates are unavailable, practitioners can adopt the COD timer app to assess 505 COD speed times.

The influence of direct oral anticoagulants on thrombin generation on Ceveron TGA

Introduction: Monitoring of direct oral anticoagulants (DOACs) with calibrated anti-Xa assay is limited by the high intra- and interindividual variation of the test results. Thrombin generation (TG) is a global hemostatic assay that reflects the patient´s individual coagulation status. The aim of this study was to investigate the influence of DOACs on TG measured with a fully automated assay system. Methods: All consecutive patients under apixaban and rivaroxaban coming to the outpatient coagulation center MVZ Limbach, Magdeburg, Germany between October 2017 and April 2020 were included. DOAC plasma levels were correlated with TG assessed using the fully automated Ceveron TG analyser. Results: A total of 703 rivaroxaban and 252 apixaban containing plasma samples were included. There was a significant correlation between DOAC plasma levels and all TG parameters except for lag time regarding apixaban. Time to peak and peak thrombin followed an exponential regression curve, while this was linear for the endogenous thrombin potential (ETP). Apixaban showed a lower correlation coefficient for all TG parameters compared to rivaroxaban and thrombin generation was less influenced by apixaban than rivaroxaban at plasma levels > 100 ng/mL. The sensitivity and negative predictive value of normal TG parameters for the prediction of DOAC plasma levels < 30 ng/mL was > 85%. Conclusion: The present data show a moderate predominantly non-linear correlation between TG parameters and plasma levels of apixaban and rivaroxaban. Rivaroxaban has a stronger effect on TG than apixaban.

Within-Group Inequality, Prediction, and the Value of Heuristics

In this chapter, I argue that groups with greater within-group variation in income are less useful as predictors of future incomes for group members. This implies that members of groups with higher levels of within-group inequality should express lower levels of linked fate and display a lower correlation between the mean group income and attitudes toward redistribution. I test this argument by examining a survey of Canada, Germany, and the United Kingdom, followed by a global sample from the World Values Survey. I close by returning to the three-country survey to show that within-region inequality does not seem to reduce regional identity.

DOP63 The Toronto IBD global endoscopic reporting (TIGER) score is well correlated with fecal calprotectin and IBD Disk in Ulcerative Colitis patients

Background Commonly used endoscopic indices in IBD lack ability to provide overall disease burden and severity, generate low inter-observer agreement, and demonstrate incomplete validation of some scores. We developed a new endoscopic reporting tool, the Toronto IBD Global Endoscopic Reporting (TIGER) score for Crohn’s disease (CD) and ulcerative colitis (UC) patients. The aim of our study was to compare the usability and validity of the TIGER score against fecal calprotectin (FC), C-reactive protein (CRP) and IBD DISK score in UC patients. Methods A cohort of 53 UC patients participated in the study. Blinded IBD experts reviewed and graded ileocolonoscopy videos. In the validation phase, the TIGER score was compared to (1) the Mayo endoscopic score serving as a reference standard and; (2) inflammatory biomarkers FC, CRP and; (3) IBD Disk. Results Inter-observer reliability of the TIGER score per segment between reviewers was excellent, Interclass Correlation Coefficient (ICC)=0.94; [95%CI: 0.92–0.96]. For categorized TIGER score, lowest overall agreement was 96.6% [95%CI: 93.5–98.6] and lowest kappa 0.91 [95%CI: 0.84–0.98], reflecting excellent agreement. Overall agreement per segment between Mayo endoscopic score and TIGER was 84% [95%CI:74%-90%] and kappa coefficient 0.60 [95%CI: 0.42–0.808]. Per subject analysis for UC yielded overall agreement of 80% [95%CI: 64–91] and kappa coefficient 0.44 [95%CI: 0.14–0.75]. There was a significant correlation between TIGER and FC (r s = .794, p &lt; .0001). There was a significant correlation between TIGER and IBD Disk (r s = .613, p &lt; .0001). As expected, there was a lower correlation between TIGER score and CRP (r s = .309, p &lt; .0850) in UC patients. Conclusion The TIGER endoscopic score demonstrates significant correlation with FC and IBD disk score in ulcerative colitis patients and thus can be used as a reliable and simple endoscopic score for UC patients to capture overall endoscopic disease burden.

What scores from monologic speaking tests can(not) tell us about interactional competence

The overarching aim of the study is to explore the extent to which test takers’ performances on monologic speaking tasks provide information about their interactional competence. This is an important concern from a test use perspective, as stakeholders tend to consider test scores as providing comprehensive information about all aspects of L2 competence. One hundred and fifty test takers completed a TOEFL iBT speaking section consisting of six monologic tasks, measuring speaking proficiency, followed by a test of interactional competence with three monologues and three dialogues, measuring pragmalinguistic skills, the ability to recipient design extended discourse, and interactional management skills. Quantitative analyses showed a medium to high correlation between TOEFL iBT speaking scores and interactional scores of r = .76, though with a much lower correlation of r = .57 for the subsample most similar to a typical TOEFL population. There was a large amount of variation in interactional scores for test takers at the same TOEFL iBT speaking score level, and qualitative analyses demonstrated that test takers’ ability to recipient design their talk and format social actions appropriate to social roles and relationships was not well captured by speaking scores. We suggest potential improvements.

The 3’-UTR Polymorphisms in the Thymidylate Synthase (TS) Gene Associated with The Risk of Ischemic Stroke and Silent Brain Infarction

Thymidylate synthase (TS) is a key gene involved in the repair of DNA damage and DNA synthesis that plays an important role in vascular development and recovery. In particular, TS gene polymorphisms play a major role in the progression of vascular disease and cancer metastasis. Therefore, the aim of this study was to investigate the association of three TS polymorphisms (1100T>C [rs699517], 1170A>G [rs2790], and 1494ins/del [rs151264360]) with ischemic stroke and silent brain infarction (SBI) in Koreans. A total of 1299 participants (507 stroke patients, 383 SBI patients, and 409 controls) were enrolled in the study. Genotyping of the three TS polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. To examine the association between TS gene polymorphisms and the diseases, we performed statistical analyses, including multivariable logistic regression and Fisher’s exact tests. We found that TS 1100T>C and 1170A>G genotypes were strongly associated with ischemic stroke and SBI susceptibility. More specifically, the TS 1100T > C polymorphism was associated with the likelihood of ischemic stroke (TT vs. CC: AOR = 2.151, 95% CI = 1.275–3.628, P = 0.004) and SBI (TT vs. TC+CC: AOR = 1.443, 95 % CI = 1.009–2.063, P = 0.045). In contrast, the TS 1170A > G polymorphism exhibited lower correlation with the risk of stroke (AA vs. GG: AOR = 0.284, 95% CI = 0.151–0.537, P < 0.0001) and SBI (AA vs. GG: AOR = 0.070, 95% CI = 0.016–0.298, P = 0.0002). Furthermore, we confirmed that the TS 1100T > C polymorphism was synergistic with low folic acid levels (AOR = 6.749, P < 0.0001). Altogether, these results suggest that TS 1100T > C and 1170A > G polymorphisms are associated with the risk of ischemic stroke and SBI, and our study provides the first evidence that 3′-UTR variants in TS are potential biomarkers in ischemic stroke and SBI.:

Diagnostic accuracy of CBCT versus intraoral imaging for assessment of peri‐implant bone defects

Background Early detection of marginal bone loss is vital for treatment planning and prognosis of teeth and implant. This study was conducted to assess diagnostic accuracy of CBCT compared to intra-oral (IO) radiography for detection, classification, and measurement of peri-implant bone defects in an animal model. Methods Fifty-four mandible blocks with implants were harvested from nine male health adult beagle dogs with acquisition of IO, CBCT and micro-CT images from all samples. Peri-implant bone defects from 16 samples were diagnosed using micro-CT and classified into 3 defect categories: dehiscence (n = 5), infrabony defect (n = 3) and crater-like defect (n = 8). Following training and calibration of the observers, they asked to detect location (mesial, distal, buccal, lingual) and shape of the defect (dehiscence, horizontal defect, vertical defect, carter-like defect) utilizing both IO and CBCT images. Both observers assessed defect depth and width on IO, CBCT and micro-CT images at each side of peri-implant bone defect via CT-analyzer software. Data were analyzed using SPSS software and a p value of < 0.05 was considered as statistically significant. Results Overall, there was a high diagnostic accuracy for detection of bone defects with CBCT images (sensitivity: 100%/100%), while IO images showed a reduction in accuracy (sensitivity: 69%/63%). Similarly, diagnostic accuracy for defect classification was significantly higher for CBCT, whereas IO images were unable to correctly identify vestibular dehiscence, with incorrect assessment of half of the infrabony defects. For accuracy of measuring defect depth and width, a higher correlation was observed between CBCT and gold standard micro-CT (r = 0.91, 95% CI 0.86–0.94), whereas a lower correlation was seen for IO images (r = 0.82, 95% CI 0.67–0.91). Conclusions The diagnostic accuracy and reliability of CBCT was found to be superior to IO imaging for the detection, classification, and measurement of peri-implant bone defects. The application of CBCT adds substantial information related to the peri-implant bone defect diagnosis and decision-making which cannot be achieved with conventional IO imaging.