Nevin Manimala

Circ Cardiovasc Imaging. 2023 Mar 3:e014671. doi: 10.1161/CIRCIMAGING.122.014671. Online ahead of print.

ABSTRACT

BACKGROUND: In hypoplastic left heart syndrome, tricuspid regurgitation (TR) is associated with circulatory failure and death. We hypothesized that the tricuspid valve (TV) structure of patients with hypoplastic left heart syndrome with a Fontan circulation and moderate or greater TR differs from those with mild or less TR, and that right ventricle volume is associated with TV structure and dysfunction.

METHODS: TV of 100 patients with hypoplastic left heart syndrome and a Fontan circulation were modeled using transthoracic 3-dimensional echocardiograms and custom software in SlicerHeart. Associations of TV structure to TR grade and right ventricle function and volume were investigated. Shape parameterization and analysis was used to calculate the mean shape of the TV leaflets, their principal modes of variation, and to characterize associations of TV leaflet shape to TR.

RESULTS: In univariate modeling, patients with moderate or greater TR had larger TV annular diameters and area, greater annular distance between the anteroseptal commissure and anteroposterior commissure, greater leaflet billow volume, and more laterally directed anterior papillary muscle angles compared to valves with mild or less TR (all P<0.001). In multivariate modeling greater total billow volume, lower anterior papillary muscle angle, and greater distance between the anteroposterior commissure and anteroseptal commissure were associated with moderate or greater TR (P<0.001, C statistic=0.85). Larger right ventricle volumes were associated with moderate or greater TR (P<0.001). TV shape analysis revealed structural features associated with TR, but also highly heterogeneous TV leaflet structure.

CONCLUSIONS: Moderate or greater TR in patients with hypoplastic left heart syndrome with a Fontan circulation is associated with greater leaflet billow volume, a more laterally directed anterior papillary muscle angle, and greater annular distance between the anteroseptal commissure and anteroposterior commissure. However, there is significant heterogeneity of structure in the TV leaflets in regurgitant valves. Given this variability, an image-informed patient-specific approach to surgical planning may be needed to achieve optimal outcomes in this vulnerable and challenging population.

PMID:36866669 | DOI:10.1161/CIRCIMAGING.122.014671

Stat Med. 2023 Mar 3. doi: 10.1002/sim.9701. Online ahead of print.

ABSTRACT

There are established methods for estimating disease prevalence with associated confidence intervals for complex surveys with perfect assays, or simple random sample surveys with imperfect assays. We develop and study methods for the complicated case of complex surveys with imperfect assays. The new methods use the melding method to combine gamma intervals for directly standardized rates and established adjustments for imperfect assays by estimating sensitivity and specificity. One of the new methods appears to have at least nominal coverage in all simulated scenarios. We compare our new methods to established methods in special cases (complex surveys with perfect assays or simple surveys with imperfect assays). In some simulations, our methods appear to guarantee coverage, while competing methods have much lower than nominal coverage, especially when overall prevalence is very low. In other settings, our methods are shown to have higher than nominal coverage. We apply our method to a seroprevalence survey of SARS-CoV-2 in undiagnosed adults in the United States between May and July 2020.

PMID:36866590 | DOI:10.1002/sim.9701

Int J Surg Pathol. 2023 Mar 3:10668969231152242. doi: 10.1177/10668969231152242. Online ahead of print.

ABSTRACT

Transmural fibrosis and stricture formation are key pathogenic processes for Crohn’s disease that underlies clinical refractoriness, resulting in severe morbidity. The mechanisms for fibroplasia in Crohn’s are not fully elucidated. In this study, we identified a cohort of refractory Crohn’s disease with surgically resected bowel specimens including cases with bowel stricture and age-/sex-matched refractory disease without bowel stricture. Via immunohistochemistry, density and distribution of IgG4+ plasma cells in resected cases were analyzed. The histologic severity of fibrosis and association with gross evidence of stricture formation and IgG4+ plasma cells were comprehensively analyzed. Our results showed that density of IgG4+ plasma cells/high-power field (IgG4+ PCs/HPF) was significantly associated with increasing histologic fibrosis score (15 IgG4+ PCs/HPF in specimens with fibrosis score 0 vs 31 IgG4+ PC/HPF in fibrosis score 2 and 3, P = .039). Patients with gross evidence of stricture had significantly higher fibrosis scores compared to those without gross evidence of stricture (P = .044). There was a trend that mean IgG4+ plasma cell count was higher in Crohn’s disease with gross stricture formation (P = .26), although it did not reach statistical significance (likely due to multiple pathogenesis events involved in bowel stricture formation besides IgG4+ plasma cells; such as transmural fibrosis, muscular hypertrophy, transmural ulcer/scar formation, and muscular-neural dysfunction). Our findings indicate IgG4+ plasma cells are associated with increasing histologic fibrosis in Crohn’s. Further research is needed to establish a role for IgG4+ plasma cells in fibroplasia with an eye toward potential medical therapies targeting IgG4+ plasma cells to prevent transmural fibrosis.

PMID:36866568 | DOI:10.1177/10668969231152242

Chem Asian J. 2023 Mar 3:e202300067. doi: 10.1002/asia.202300067. Online ahead of print.

ABSTRACT

Halogen⋯halogen interaction is a highly debated and important topic in crystal engineering and supramolecular chemistry. There are controversies about the nature and geometry of these interactions. F, Cl, Br and I are the four halogens that involve in these interactions. Very often the lighter and the heavier halogens behave differently. The nature of the interactions also depends upon the nature of the atom which is covalently bonded to the halogens. In this review different homo-halogen⋯halogen, hetero-halogen⋯halogen, halogen⋯halide interactions, their natures, and preferred geometries have been discussed. Different motifs of halogen⋯halogen interactions, interchangeability of the halogen⋯halogen interactions with other supramolecular synthons and interchangeability between different halogens and other functional groups also have been discussed. Some of the important applications, in which halogen⋯halogen interactions have been successfully employed, are mentioned.

PMID:36866564 | DOI:10.1002/asia.202300067

Front Biosci (Landmark Ed). 2023 Feb 20;28(2):30. doi: 10.31083/j.fbl2802030.

ABSTRACT

BACKGROUND: Obesity results from a chronic imbalance between energy intake and energy expenditure. Total energy expenditure for all physiological functions combined can be measured approximately by calorimeters. These devices assess energy expenditure frequently (e.g., in 60-second epochs), resulting in massive complex data that are nonlinear functions of time. To reduce the prevalence of obesity, researchers often design targeted therapeutic interventions to increase daily energy expenditure.

METHODS: We analyzed previously collected data on the effects of oral interferon tau supplementation on energy expenditure, as assessed with indirect calorimeters, in an animal model for obesity and type 2 diabetes (Zucker diabetic fatty rats). In our statistical analyses, we compared parametric polynomial mixed effects models and more flexible semiparametric models involving spline regression.

RESULTS: We found no effect of interferon tau dose (0 vs. 4 μg/kg body weight/day) on energy expenditure. The B-spline semiparametric model of untransformed energy expenditure with a quadratic term for time performed best in terms of the Akaike information criterion value.

CONCLUSIONS: To analyze the effects of interventions on energy expenditure assessed with devices that collect data at frequent intervals, we recommend first summarizing the high dimensional data into epochs of 30 to 60 minutes to reduce noise. We also recommend flexible modeling approaches to account for the nonlinear patterns in such high dimensional functional data. We provide freely available R codes in GitHub.

PMID:36866554 | DOI:10.31083/j.fbl2802030

Front Biosci (Landmark Ed). 2023 Feb 22;28(2):31. doi: 10.31083/j.fbl2802031.

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic and so it is crucial the right evaluation of viral infection. According to the Centers for Disease Control and Prevention (CDC), the Real-Time Reverse Transcription PCR (RT-PCR) in respiratory samples is the gold standard for confirming the disease. However, it has practical limitations as time-consuming procedures and a high rate of false-negative results. We aim to assess the accuracy of COVID-19 classifiers based on Arificial Intelligence (AI) and statistical classification methods adapted on blood tests and other information routinely collected at the Emergency Departments (EDs).

METHODS: Patients admitted to the ED of Careggi Hospital from April 7th-30th 2020 with pre-specified features of suspected COVID-19 were enrolled. Physicians prospectively dichotomized them as COVID-19 likely/unlikely case, based on clinical features and bedside imaging support. Considering the limits of each method to identify a case of COVID-19, further evaluation was performed after an independent clinical review of 30-day follow-up data. Using this as a gold standard, several classifiers were implemented: Logistic Regression (LR), Quadratic Discriminant Analysis (QDA), Random Forest (RF), Support Vector Machine (SVM), Neural Networks (NN), K-nearest neighbor (K-NN), Naive Bayes (NB).

RESULTS: Most of the classifiers show a ROC >0.80 on both internal and external validation samples but the best results are obtained applying RF, LR and NN. The performance from the external validation sustains the proof of concept to use such mathematical models fast, robust and efficient for a first identification of COVID-19 positive patients. These tools may constitute both a bedside support while waiting for RT-PCR results, and a tool to point to a deeper investigation, by identifying which patients are more likely to develop into positive cases within 7 days.

CONCLUSIONS: Considering the obtained results and with a rapidly changing virus, we believe that data processing automated procedures may provide a valid support to the physicians facing the decision to classify a patient as a COVID-19 case or not.

PMID:36866553 | DOI:10.31083/j.fbl2802031

Front Biosci (Landmark Ed). 2023 Feb 16;28(2):29. doi: 10.31083/j.fbl2802029.

ABSTRACT

BACKGROUND: The Apoptotic protease activating factor 1 (Apaf-1) protein, as one of the factors involved in the activation of the mitochondrial apoptotic pathway, plays an important role in cancer biology. Apaf-1 expression in tumour cells has been shown to be downregulated, with significant implications for tumour progression. Hence, we investigated the expression of Apaf-1 protein in the Polish population of patients with colon adenocarcinoma without any therapy prior to radical surgery. Moreover, we assessed the relation between Apaf-1 protein expression and the clinicopathological factors. The prognostic activity of this protein was analyzed in relation to 5-year survival of patients. In order to show the localization of Apaf-1 protein at the cellular level, the immunogold labelling method was used.

METHODS: The study was conducted using the colon tissue material from patients with histopathologically confirmed colon adenocarcinoma. Immunohistochemical expression of Apaf-1 protein was performed using Apaf-1 antibody at dilution 1:600. The associations between the immunohistochemistry (IHC) expression of Apaf-1 and clinical parameters were analyzed using the Chi2 test and Chi2Yatesa test. Kaplan-Meier analysis and the log-rank test were used to verify the relationship between the intensity of Apaf-1 expression and 5-year survival rate of patients. The results were considered statistically significant when p < 0.05.

RESULTS: Apaf-1 expression was evaluated by immunohistochemical staining in whole tissue sections. Thirty-nine (33.23%) samples had strong Apaf-1 protein expression and 82 (67.77%) samples were characterized by low expression. The high expression of Apaf-1 was clearly correlated with the histological grade of the tumour (p = 0.001), proliferating cell nuclear antigen (PCNA) immunohistochemical expression (p = 0.005), age (p = 0.015), depth of invasion (p < 0.001) and angioinvasion (p < 0.001). The 5-year survival rate was significantly higher in the group of patients with high expression of this protein (log-rank, p < 0.001).

CONCLUSIONS: We can conclude that Apaf-1 expression is positively correlated with reduced survival of colon adenocarcinoma patients.

PMID:36866552 | DOI:10.31083/j.fbl2802029

J Phycol. 2023 Mar 3. doi: 10.1111/jpy.13326. Online ahead of print.

ABSTRACT

Viet Nam has a coastline of 3,200 km with thousands of islands providing diverse habitats for benthic harmful algal species including species of Gambierdiscus. Some of these species produce ciguatera toxins, which may accumulate in large carnivore fish potentially posing major threats to public health. This study reports five species of Gambierdiscus from Vietnamese waters, notably G. australes, G. caribaeus, G. carpenteri, G. pacificus, and G. vietnamensis sp. nov. All species are identified morphologically by LM and SEM, and identifications are supported by molecular analyses of nuclear rDNA (D1-D3 and D8-D10 domains of LSU, SSU, and ITS1-5.8S-ITS2 region) based on cultured material collected during 2010-2021. Statistical analyses of morphometric measurements may be used to differentiate some species if a sufficiently large number of cells are examined. Gambierdiscus vietnamensis sp. nov. is morphologically similar to other strongly reticulated species, such as G. belizeanus and possibly G. pacificus; the latter species is morphologically indistinguishable from G. vietnamensis sp. nov., but they are genetically distinct, and molecular analysis is deemed necessary for proper identification of the new species. This study also revealed that strains denoted G. pacificus from Hainan Island (China) should be included in G. vietnamensis sp. nov.

PMID:36866508 | DOI:10.1111/jpy.13326

Cytometry A. 2023 Mar 3. doi: 10.1002/cyto.a.24728. Online ahead of print.

ABSTRACT

Förster resonance energy transfer (FRET) is a radiationless interaction between a donor and an acceptor whose distance dependence makes it a sensitive tool for studying the oligomerization and the structure of proteins. When FRET is determined by measuring the sensitized emission of the acceptor, a parameter characterizing the ratio of detection efficiencies of an excited acceptor vs. an excited donor is invariably involved in the formalism. For FRET measurements involving fluorescent antibodies or other external labels, this parameter, designated by α, is usually determined by comparing the intensity of a known number of donors and acceptors in two independent samples leading to a large statistical variability if the sample size is small. Here, we present a method that improves precision by applying microbeads with a calibrated number of antibody binding sites and a donor-acceptor mixture in which donors and acceptors are present in a certain, experimentally determined ratio. A formalism is developed for determining α and the superior reproducibility of the proposed method compared to the conventional approach is demonstrated. Since the novel methodology does not require sophisticated calibration samples or special instrumentation, it can be widely applied for the quantification of FRET experiments in biological research.

PMID:36866503 | DOI:10.1002/cyto.a.24728

Gerontologist. 2023 Mar 2:gnad021. doi: 10.1093/geront/gnad021. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: The Veterans RAND 12-Item Health Survey (VR-12) is a generic patient-reported outcome measure of physical and mental health status. An adapted version of the VR-12 was developed for use with older adults living in long-term residential care (LTRC) homes in Canada: VR-12 (LTRC-C). This study aimed to evaluate the psychometric validity of the VR-12 (LTRC-C).

RESEARCH DESIGN AND METHODS: Data for this validation study were collected via in-person interviews for a province-wide survey of adults living in LTRC homes across British Columbia (N = 8,657). Three analyses were conducted to evaluate validity and reliability: 1) confirmatory factor analyses (CFA) were conducted to validate the measurement structure, 2) correlations with measures of depression, social engagement and daily activities were examined to evaluate convergent and discriminant validity and 3) Cronbach’s alpha (r) statistics were obtained to evaluate internal consistency reliability.

RESULTS: A measurement model with two correlated latent factors (representing physical health and mental health), four cross-loadings, and four correlated items resulted in acceptable fit (Root Mean Square Error of Approximation = .07; Comparative Fit Index = .98). Physical and mental health were correlated in expected directions with measures of depression, social engagement, and daily activities, though magnitudes of the correlations were quite small. Internal consistency reliability was acceptable for physical and mental health (r >0.70).

DISCUSSION AND IMPLICATIONS: This study supports the use of the VR-12 (LTRC-C) to measure perceived physical and mental health among older adults living in LTRC homes.

PMID:36866495 | DOI:10.1093/geront/gnad021