Development of Urinary Diagnostic Biomarker for IgA Nephropathy by Lectin Microarray

<b><i>Introduction:</i></b> The pathogenic roles of aberrantly glycosylated IgA1 have been reported. However, it is unexplored whether the profiling of urinary glycans contributes to the diagnosis of IgAN. <b><i>Methods:</i></b> We conducted a retrospective study enrolling 493 patients who underwent renal biopsy at Okayama University Hospital between December 2010 and September 2017. We performed lectin microarray in urine samples and investigated whether c-statistics of the reference standard diagnosis model employing hematuria, proteinuria, and serum IgA were improved by adding the urinary glycan intensity. <b><i>Results:</i></b> Among 45 lectins, 3 lectins showed a significant improvement of the models: <i>Amaranthus caudatus</i> lectin (ACA) with the difference of c-statistics 0.038 (95% CI: 0.019–0.058, <i>p</i> &#x3c; 0.001), <i>Agaricus bisporus</i> lectin (ABA) 0.035 (95% CI: 0.015–0.055, <i>p</i> &#x3c; 0.001), and <i>Maackia amurensis</i> lectin (MAH) 0.035 (95% CI: 0.015–0.054, <i>p</i> &#x3c; 0.001). In 3 lectins, each signal plus reference standard showed good reclassification (category-free NRI and relative IDI) and good model fitting associated with the improvement of AIC and BIC. Stratified by eGFR, the discriminatory ability of ACA plus reference standard was maintained, suggesting the robust renal function-independent diagnostic performance of ACA. By decision curve analysis, there was a 3.45% net benefit by adding urinary glycan intensity of ACA to the reference standard at the predefined threshold probability of 40%. <b><i>Conclusions:</i></b> The reduction of Gal(β1-3)GalNAc (T-antigen), Sia(α2-3)Gal(β1-3)GalNAc (Sialyl T), and Sia(α2-3)Gal(β1-3)Sia(α2-6)GalNAc (disialyl-T) was suggested by binding specificities of 3 lectins. C1GALT1 and COSMC were responsible for the biosynthesis of these glycans, and they were known to be downregulated in IgAN. The urinary glycan analysis by ACA is a useful and robust noninvasive strategy for the diagnosis of IgAN.

Bifurcation functional significance score as predictor of mortality: a validating study

Considerable progress has been made in the treatment of coronary bifurcation stenosis. Anatomical characteristics of the vessel and lesion, however, fail to give information about the functional significance of the bifurcation stenosis. To the best of our knowledge, there is no study that systematically establishes the baseline functional significance of coronary stenosis and its effect on procedural and clinical outcomes. Patients with significant angiographic bifurcation lesions defined as diameter stenosis > 50% in main vessel and/or side branch were included. FFR was performed in main vessel (MV) and side branch (SB) before and after percutaneous coronary intervention (PCI). 169 patients from Fiesta study (derivation cohort) and 555 patients from prospective bifurcation registry (clinical effect cohort) were analyzed to validate angiographic prediction score (BFSS) used to determine the potentially functional significance of coronary bifurcation stenosis. Bifurcation functional significance score (including the following parameters—SYNTAX ≥ 11, SB/MB BARI score, MV %DS ≥ 55%, main branch (MB) %DS ≥ 65%, lesion length ≥ 25 mm) with a maximum value of 11 was developed. A cut-off value of 6.0 was shown to give the best discriminatory ability—with accuracy 87% (sensitivity 77%, specificity 96%, p < 0.001). There was also a significant difference in all-cause mortality between patients with BFSS ≥ 6.0 vs. BFSS < 6.0–25.5% vs. 18.4%, log-rank p = 0.001 as well as cardiac mortality: BFSS ≥ 6.0 vs. BFSS < 6.0–17.7% vs. 14.5%, log-rank (p = 0.016). The cardiac mortality was significantly lower in patients with smaller absolute SB territory, p = 0.023. An angiographic score (BFSS) with good discriminatory ability to determine the functional significance of coronary bifurcation stenosis was developed. The value for BFSS ≥ 6.0 can be used as a discriminator to define groups with higher risk for all-cause and cardiac mortality. Also, we found that the smaller side branches pose greater mortality risk.

Comprehensive analysis identifies IFI16 as a novel signature associated with overall survival and immune infiltration of skin cutaneous melanoma

Background Skin cutaneous melanoma (SKCM) is the most common skin tumor with high mortality. The unfavorable outcome of SKCM urges the discovery of prognostic biomarkers for accurate therapy. The present study aimed to explore novel prognosis-related signatures of SKCM and determine the significance of immune cell infiltration in this pathology. Methods Four gene expression profiles (GSE130244, GSE3189, GSE7553 and GSE46517) of SKCM and normal skin samples were retrieved from the GEO database. Differentially expressed genes (DEGs) were then screened, and the feature genes were identified by the LASSO regression and Boruta algorithm. Survival analysis was performed to filter the potential prognostic signature, and GEPIA was used for preliminary validation. The area under the receiver operating characteristic curve (AUC) was obtained to evaluate discriminatory ability. The Gene Set Variation Analysis (GSVA) was performed, and the composition of the immune cell infiltration in SKCM was estimated using CIBERSORT. At last, paraffin-embedded specimens of primary SKCM and normal skin tissues were collected, and the signature was validated by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Results Totally 823 DEGs and 16 feature genes were screened. IFI16 was identified as the signature associated with overall survival of SKCM with a great discriminatory ability (AUC > 0.9 for all datasets). GSVA noticed that IFI16 might be involved in apoptosis and ultraviolet response in SKCM, and immune cell infiltration of IFI16 was evaluated. At last, FISH and IHC both validated the differential expression of IFI16 in SKCM. Conclusions In conclusion, our comprehensive analysis identified IFI16 as a signature associated with overall survival and immune infiltration of SKCM, which may play a critical role in the occurrence and development of SKCM.

Legalization of Bride measure to detect talented children in kindergarten in Damascus governorate: تقنين مقياس برايد PRIDE للكشف عن الأطفال الموهوبين بمرحلة الروضة بمحافظة دمشق

This research aims to identify the methods of detection and diagnosis of gifted children in pre-school stage, where a modified Syrian image was developed on the BRIDE scale for the detection of gifted in pre-school stage, with indications of validity, stability, and effectiveness of the Syrian environment paragraphs. The process of preparing the scale included a number of stages and procedures, represented in preparing an image of the scale and reviewing it by a number of arbitrators in the Department of Special Education and Educational and Psychological Measurement and Evaluation, and then applying that image to a sample of 100 boys and girls representing a number of kindergartens in Damascus governorate. Then, the data resulting from the application process was analyzed, and indications were reached about the discriminatory honesty, as it was found that there is a difference in favor of the first group (higher) whose average is greater, and this indicates that the scale is characterized by a discriminatory ability in favor of the higher group in the total score of the scale, The validity of the inter-correlations was studied and it was found that most of the correlations of the items of the scale are significant at the significance level (0.01) and the significance level (0.05), and the spoken honesty was studied with the significance of another criterion, which is the Stanford test, which shows the fifth standardized picture on the Syrian environment and fig. The values ​​of the correlation of the verbal knowledge test with the domains of the Pride scale and its total score ranged between (0.819-0.387), while we notice the correlation values ​​with the matrix test (0.836-0.318). As for the indicators of scale stability, it was calculated in two ways, namely, the repeat method (0.915) and the half-segment method (0.892).

Validation of AD8-Philippines (AD8-P): A Brief Informant-Based Questionnaire for Dementia Screening in the Philippines

Aim. This study was aimed at validating the Filipino version of AD8 (AD8-P). Methods. Community-dwelling Filipino older persons aged ≥60 years, together with their informants, participated in this study. Psychologists independently interviewed the informants with AD8-P and administered the Filipino-validated Mini-Mental State Examination (MMSE-P) and Montreal Cognitive Assessment (MoCA-P) to the older persons. Neurologists and geriatrician conducted physical and neurological examination and Clinical Dementia Rating™ (CDR™) to determine cognitive diagnosis and were blinded with the results of AD8-P. Dementia was diagnosed based on DSM-IV-TR criteria. AD8-P discriminatory ability to screen for dementia was evaluated according to DSM-IV-TR diagnostic criteria for dementia. Results. A total of 366 community-dwelling Filipino older persons aged ≥60 years, 213 with normal cognition and 153 with dementia, and their informants were included in this study. Majority (90%) were at the mildest stage of dementia. Area under the receiver-operating-characteristic curve (AUROC) for AD8-P was 0.94 (95% CI 0.92 to 0.96), demonstrating excellent overall predictive power to screen for dementia. The optimal AD8-P cut-off score with best balance sensitivity (91.5%) and specificity (77.9%) was ≥3. Conclusion. AD8-P demonstrated good psychometric properties to screen for dementia, even at the earliest stage of cognitive decline.

Psychometric Properties of Rapid Word-Based Rate Measures in the Assessment of Bulbar Amyotrophic Lateral Sclerosis: Comparisons With Syllable-Based Rate Tasks

Purpose Rapid maximum performance repetition tasks have increasingly demonstrated their utility as clinimetric markers supporting diagnosis and monitoring of bulbar disease in amyotrophic lateral sclerosis (ALS). A recently developed protocol uses novel real-word repetitions instead of traditional nonword/syllable sequences in hopes of improving sensitivity to motor speech impairments by adding a phonological target constraint that would activate a greater expanse of the motor speech neuroanatomy. This study established the psychometric properties of this novel clinimetric protocol in its assessment of bulbar ALS and compared performance to traditional syllable sequence dysdiadochokinetic (DDK) tasks. Specific objectives were to (a) compare rates between controls and speakers with symptomatic versus presymptomatic bulbar disease, (b) characterize their discriminatory ability in detecting presymptomatic bulbar disease compared to healthy speech, (c) determine their articulatory movement underpinnings, and (d) establish within-individual longitudinal changes. Method DDK and novel tongue (“ticker”—TAR) and labial (“pepper”—LAR) articulatory rates were compared between n = 18 speakers with presymptomatic bulbar disease, n = 10 speakers with symptomatic bulbar disease, and n = 13 healthy controls. Bulbar disease groups were determined by a previously validated speaking rate cutoff. Discriminatory ability was determined using receiver operating characteristic analysis. Within-individual change over time was characterized in a subset of 16 participants with available longitudinal data using linear mixed-effects models. Real-time articulatory movements of the tongue front, tongue dorsum, jaw, and lips were captured using 3-D electromagnetic articulography; effects of movement displacement and speed on clinimetric rates were determined using stepwise linear regressions. Results All clinimetric rates (traditional DDK tasks and novel tasks) were reduced in speakers with symptomatic bulbar disease; only TAR was reduced in speakers with presymptomatic bulbar disease and was able to detect this group with an excellent discrimination ability (area under the curve = 0.83). Kinematic analyses revealed associations with expected articulators, greater motor complexity, and differential articulatory patterns for the novel real-word repetitions than their DDK counterparts. Only LAR significantly declined longitudinally over the disease course. Conclusion Novel real-word clinimetric rate tasks evaluating tongue and labial articulatory dysfunction are valid and effective markers for early detection and tracking of bulbar disease in ALS.

Real-world observational study of assessment of CHA2DS2-VASc, C2HEST and HAVOC scores for atrial fibrillation among patients with rheumatological disorders: a nationwide analysis

PurposeThis is a nationwide-based retrospective study aiming to compare the three different scoring systems (CHA2DS2-VASc, C2HEST and HAVOC scores) in the prediction of atrial fibrillation (AF) in patients with rheumatological disease.MethodsWe used the Fine and Gray model to estimate the risk of AF (subhazard ratio and 95% CI). The predictive accuracy and discriminatory ability of the predictive model were evaluated by receiver operating characteristic (ROC) curve.ResultsAmong the three predictive models, the model using CHA2DS2-VASc score had the better discriminative ability with an ROC of 0.79. The model with C2HEST score had an ROC of 0.78. The discriminative ability of the HAVOC score was 0.77, estimated by ROC.ConclusionWe concluded the CHA2DS2-VASc score has better performance in predicting AF compared with C2HEST score or HAVOC score.

Concordance Probability for Insurance Pricing Models

The concordance probability, also called the C-index, is a popular measure to capture the discriminatory ability of a predictive model. In this article, the definition of this measure is adapted to the specific needs of the frequency and severity model, typically used during the technical pricing of a non-life insurance product. For the frequency model, the need of two different groups is tackled by defining three new types of the concordance probability. Secondly, these adapted definitions deal with the concept of exposure, which is the duration of a policy or insurance contract. Frequency data typically have a large sample size and therefore we present two fast and accurate estimation procedures for big data. Their good performance is illustrated on two real-life datasets. Upon these examples, we also estimate the concordance probability developed for severity models.

Reliability and validity of the mean flow index (Mx) for assessing cerebral autoregulation in humans: A systematic review of the methodology

Cerebral autoregulation is a complex mechanism that serves to keep cerebral blood flow relatively constant within a wide range of cerebral perfusion pressures. The mean flow index (Mx) is one of several methods to assess dynamic cerebral autoregulation, but its reliability and validity have never been assessed systematically. The purpose of the present systematic review was to evaluate the methodology, reliability and validity of Mx. Based on 128 studies, we found inconsistency in the pre-processing of the recordings and the methods for calculation of Mx. The reliability in terms of repeatability and reproducibility ranged from poor to excellent, with optimal repeatability when comparing overlapping recordings. The discriminatory ability varied depending on the patient populations; in general, those with acute brain injury exhibited a higher Mx than healthy volunteers. The prognostic ability in terms of functional outcome and mortality ranged from chance result to moderate accuracy. Since the methodology was inconsistent between studies, resulting in varying reliability and validity estimates, the results were difficult to compare. The optimal method for deriving Mx is currently unknown.

Prediction of Cerebral Amyloid Pathology Based on Plasma Amyloid and Tau Related Markers

Background and Purpose: Pyroglutamate-modified β-amyloid peptide (AβpE) is crucial for AD pathophysiological process. The potential associations of plasma AβpE and total tau (t-tau) with brain Aβ burden and cognitive performance remain to be clarified.Methods: Forty-six subjects with unimpaired cognition, mild cognitive impairment, or very mild dementia were enrolled. Plasma levels of AβpE3−40, t-tau, and Aβ42 were quantified by immunomagnetic reduction (IMR) assays. We analyzed individual and combined biomarker correlations with neuropsychological scores and Aβ positivity determined by 18F-florbetapir positron emission tomography (PET).Results: Both plasma AβpE3−40 levels and AβpE3−40/t-tau ratios correlated negatively with short-term memory and global cognition scores, while correlating positively with PET standardized uptake value ratios (SUVRs). Among the biomarkers analyzed, the combination of AβpE3−40 in a ratio with t-tau had the best discriminatory ability for Aβ PET positivity. Likewise, logistic regression analysis showed that AβpE3−40/t-tau was a highly robust predictor of Aβ PET positivity after controlling for relevant demographic covariates.Conclusion: Plasma AβpE3−40/t-tau ratios correlate with cognitive function and cerebral Aβ burden. The suitability of AβpE3−40/t-tau as a candidate clinical biomarker of AD pathology in the brain should be examined further in larger studies.