Synthetic Data Resource and Benchmarks for Time Cell Analysis and Detection Algorithms

Hippocampal CA1 cells take part in reliable, time-locked activity sequences in tasks that involve an association between stimuli, in a manner that tiles the interval between the stimuli. Such cells have been termed time cells. Here we adopt a first-principles approach to comparing diverse analysis and detection algorithms for identifying time cells. We developed a resource for generating synthetic activity datasets using calcium signals recorded in vivo from mouse hippocampus using 2-photon imaging, for template response waveforms. We assigned known, ground truth values for properties of time cells in this synthetic dataset, including noise, timing imprecision, hit-trial ratio and calcium event width. These datasets were the input to a pipeline for testing multiple algorithms for time cell detection to determine the conditions for which they were best suited, and evaluate their effective operating ranges. We find that most algorithms are sensitive to noise. Only a few methods benefit from larger event widths. Reassuringly, most methods are insensitive to timing imprecision, and exhibit successful time cell detection even at low hit trial ratios. Importantly, all methods show good concordance in identifying cells as time cells.

Accuracy investigation of Fused Deposition Modelling (FDM) processed ABS and ULTRAT parts.

This paper aims to assess the dimensional deviation of Fused Deposition Modeling (FDM) processed ABS and ULTRAT parts using a new geometrical model which can evaluate three types of dimensional deviation: along the z-axis, along external and internal dimensions, and through diameters. The methodology involves a step-by-step procedure wherein after establishing the experimental plan and manufacturing the specimens, the measurements taken are analyzed via Grey Relational Analysis (GRA) to find out the optimal combination of parameters leading to the minimum deviation in all dimensions of parts for both materials. Statistical techniques such as Analysis of Variance (ANOVA) and Signal to Noise (S/N) ratio were also used. Subsequently, a confirmation test was carried out to validate the results obtained. The findings of the ANOVA and the S/N ratio were in good concordance with those of GRA.

Analytical evaluation of the Nittobo Medical tartrate resistant acid phosphatase isoform 5b (TRACP-5b) EIA and comparison with IDS iSYS in different clinically defined populations

Objectives Tartrate-resistant acid phosphatase, isoform 5b (TRACP-5b) is a bone resorption marker not influenced by renal function or food intake. TRACP-5b can be measured with Nittobo Medical enzymatic-immunoassay and IDS-iSYS automated immunoassay. We evaluated the Nittobo assay and established reference ranges for a Western-European population. We compared Nittobo and IDS results in different well-defined clinical populations. Methods We established the limits of detection and quantification (LOD-LOQ), linearity, imprecision and the reference ranges in 119 males, 50 women (<45 years) and 120 women (>60 years) for TRACP-5b with the Nittobo assay. We compared both assays in 30 hemodialyzed (HD), and 40 stage 3–5 patients suffering from chronic kidney disease (CKD), 40 patients suffering from rheumatoid arthritis and osteoporosis and 80 post-menopausal women. We measured TRACP-5b, β-crosslaps (β-CTX), bone alkaline phosphatase (B-ALP) and PTH in 20 hemodialyzed (HD) and 40 CKD patients. Results LOD and LOQ were 0.02 and 0.35 U/L. CV ranged from 8.3 to 4.3% (2/5 samples presenting CV > desirable CV). Method was linear up to of 11.3 U/L. Upper and lower limits of normality were 0.8–7.6 U/L in men, 0.9–4.7 U/L in women <45 and 0.9–7.1 U/L in women >60. The regression equation between the 2 methods was Nittobo = 1.13 (95% CI: 1.09–1.16) × iSYS − 0.4 (95% CI: −0.5; −0.3). TRACP-5b and b-ALP were in their respective reference ranges for most of CKD and HD patients. That was not the case for β-CTX, which increased with decreasing eGFR. Conclusions Nittobo TRACP-5b presents interesting analytical features and a good concordance with IDS iSYS. These methods could thus potentially be harmonized.

Temporal and genomic analysis of additive genetic variance in breeding programmes

Genetic variance is a central parameter in quantitative genetics and breeding. Assessing changes in genetic variance over time as well as the genome is therefore of high interest. Here, we extend a previously proposed framework for temporal analysis of genetic variance using the pedigree-based model, to a new framework for temporal and genomic analysis of genetic variance using marker-based models. To this end, we describe the theory of partitioning genetic variance into genic variance and within-chromosome and between-chromosome linkage-disequilibrium, and how to estimate these variance components from a marker-based model fitted to observed phenotype and marker data. The new framework involves three steps: (i) fitting a marker-based model to data, (ii) sampling realisations of marker effects from the fitted model and for each sample calculating realisations of genetic values and (iii) calculating the variance of sampled genetic values by time and genome partitions. Analysing time partitions indicates breeding programme sustainability, while analysing genome partitions indicates contributions from chromosomes and chromosome pairs and linkage-disequilibrium. We demonstrate the framework with a simulated breeding programme involving a complex trait. Results show good concordance between simulated and estimated variances, provided that the fitted model is capturing genetic complexity of a trait. We observe a reduction of genetic variance due to selection and drift changing allele frequencies, and due to selection inducing negative linkage-disequilibrium.

Validation of Plasma Amyloid-β 42/40 for Detecting Alzheimer Disease Amyloid Plaques

Objective:To determine the diagnostic accuracy of a plasma Aβ42/Aβ40 assay in classifying amyloid PET status across global research studies using samples collected by multiple centers that utilize different blood collection and processing protocols.Methods:Plasma samples (n=465) were obtained from three large Alzheimer’s Disease (AD) research cohorts in the US (n=182), Australia (n=183), and Sweden (n=100). Plasma Aβ42/Aβ40 was measured by a high precision immunoprecipitation mass spectrometry (IPMS) assay and compared to the reference standards of amyloid PET and CSF Aβ42/Aβ40.Results:In the combined cohort of 465 participants, plasma Aβ42/Aβ40 had good concordance with amyloid PET status (Receiver Operating Characteristic Area Under the Curve [AUC] of 0.84, 95% confidence interval [CI] 0.80-0.87); concordance improved with the inclusion of APOE ε4 status (AUC 0.88, 95% CI 0.85-0.91). The AUC of plasma Aβ42/Aβ40 with CSF amyloid status was 0.85 (95% CI 0.78-0.91) and improved to 0.93 (95% CI 0.89-0.97) with APOE ε4 status. These findings were consistent across the three cohorts, despite differences in protocols. Further, the assay performed similarly in both cognitively unimpaired and impaired individuals.Conclusions:Plasma Aβ42/Aβ40 is a robust measure for detecting amyloid plaques and can be utilized to aid in the diagnosis of AD, identify those at risk for future dementia due to AD, and improve the diversity of populations enrolled in AD research and clinical trials.Classification of Evidence:This study provides Class II evidence that plasma Aβ42/Aβ40, as measured by a high precision IPMS assay, accurately diagnoses brain amyloidosis in both cognitively unimpaired and impaired research participants.

Comparison of the TOFscan and the TOF-Watch SX during pediatric neuromuscular function recovery: a prospective observational study

Background TOFscan is a three-dimensional acceleromyography neuromuscular monitoring device that does not require initial calibration before muscle relaxant injection. This study aimed to compare TOFscan with TOF-Watch SX, the currently widely accepted uni-dimensional acceleromyography, for use among the pediatric population. We aimed to assess the agreement between TOFscan with TOF-Watch SX in the pediatric population’s neuromuscular recovery. Methods A total of 35 children aged 6–12 years were enrolled. Prior to any muscle relaxant injection, TOFscan and TOF-Watch SX were applied at each opposite arm and monitoring began concurrently throughout neuromuscular recovery. Calibration was performed for TOF-Watch SX, and train-of-four values were recorded every 15 s. Agreement between the two devices was evaluated with Modified Bland-Altman analysis. Results The bias between TOF-Watch SX and TOFscan were all within the 95% limits of agreement. The bias and standard deviation were smaller and the limit of agreement was narrower in the normalized group than in the non-normalized group [normalized bias −0.002 (95% CI, −0.013 to 0.010), standard deviation (SD) 0.111 vs non-normalized bias 0.010 (95% CI, −0.003 to 0.0236), SD 0.127]. Conclusions TOFscan reliably demonstrated lack of bias and good concordance with TOF-Watch SX throughout the neuromuscular recovery, especially when normalized. Despite technical limitations, the two devices were unbiased along the path of spontaneous and pharmacological reversal in pediatric patients. Trial registration ClinicalTrials.gov NCT03775603. Registered on 13 March 2018

A nomogram model for predicting prognosis of obstructive colorectal cancer

Background The prognosis of obstructive colorectal cancer (oCRC) is worse than that of nonobstructive colorectal cancer. However, no previous study has established an individualized prediction model for the prognosis of patients with oCRC. We aimed to screen the factors that affect the prognosis of oCRC and to use these findings to establish a nomogram model that predicts the individual prognosis of patients with oCRC. Methods This retrospective study collected data of 181 patients with oCRC from three medical hospitals between February 2012 and December 2017. Among them, 129 patients from one hospital were used as the training cohort. Univariate and multivariate analyses were used in this training cohort to select independent risk factors that affect the prognosis of oCRC, and a nomogram model was established. The other 52 patients from two additional hospitals were used as the validation cohort to verify the model. Results Multivariate analysis showed that carcinoembryonic antigen level (p = 0.037, hazard ratio [HR] = 2.872 [1.065–7.740]), N stage (N1 vs. N0, p = 0.028, HR = 3.187 [1.137–8.938]; N2 vs. N0, p = 0.010, HR = 4.098 [1.393–12.051]), and surgical procedures (p = 0.002, HR = 0.299 [0.139–0.643]) were independent prognostic factors of overall survival in patients with oCRC. These factors were used to construct the nomogram model, which showed good concordance and accuracy. Conclusion Carcinoembryonic antigen, N stage, and surgical method are independent prognostic factors for overall survival in patients with oCRC, and the nomogram model can visually display these results.

Development and Validation of a Graded Motor Imagery Intervention for Phantom Limb Pain in Patients with Amputations (GraMI Protocol): A Delphi Study

Background: Phantom limb pain can be defined as discomfort or pain in a missing part of the limb. The aims of this study were to develop and validate, through a Delphi methodology, a graded motor imagery protocol in order to reduce phantom limb pain. Method: Physiotherapists and/or occupational therapists with experience in research and a minimum clinical experience of five years in the field of neurorehabilitation and/or pain were recruited by part of a group of experts to assess the intervention. The study was conducted through an online questionnaire, where experts assessed each aspect of the intervention through a Likert scale. As many rounds as necessary were carried out until consensus was reached among experts. Results: A total of two rounds were required to fully validate the intervention. During the second round, the relative interquartile range of all aspects to be assessed was less than 15%, thus showing a consensus among experts and with good concordance (Kappa index of 0.76). Conclusion: Experts validated a graded motor imagery intervention of phantom limb pain in patients with amputations (GraMi protocol). This intervention can help to homogenize the use of graded motor imagery in future studies and in clinical practice.

Necroptosis-Related lncRNAs: Predicting Prognosis and the Distinction between the Cold and Hot Tumors in Gastric Cancer

Background. In the face of poor prognosis and immunotherapy failure of gastric cancer (GC), this project tried to find new potential biomarkers for predicting prognosis and precision medication to ameliorate the situation. Methods. To form synthetic matrices, we retrieved stomach adenocarcinoma transcriptome data from Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA). Necroptosis-related prognostic lncRNA was identified by coexpression analysis and univariate Cox regression. Then we performed the least absolute shrinkage and selection operator (LASSO) to construct the necroptosis-related lncRNA model. Next, the Kaplan–Meier analysis, time-dependent receiver operating characteristics (ROC), univariate Cox (uni-Cox) regression, multivariate Cox (multi-Cox) regression, nomogram, and calibration curves were made to verify and evaluate the model. Gene set enrichment analyses (GSEA), principal component analysis (PCA), immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) in risk groups were also analyzed. For further discussing immunotherapy between the cold and hot tumors, we divided the entire set into two clusters based on necroptosis-related lncRNAs. Results. We constructed a model with 16 necroptosis-related lncRNAs. In the model, we found the calibration plots showed a good concordance with the prognosis prediction. The area’s 1-, 2-, and 3-year OS under the ROC curve (AUC) were 0.726, 0.763, and 0.770, respectively. Risk groups could be a guide of systemic treatment because of significantly different IC50 between risk groups. Above all, clusters could help distinguish between the cold and hot tumors effectively and contribute to precise mediation. Cluster 2 was identified as the hot tumor and more susceptible to immunotherapeutic drugs. Conclusion. The results of this project supported that necroptosis-related lncRNAs could predict prognosis and help make a distinction between the cold and hot tumors for improving individual therapy in GC.

Development of a nomogram for predicting the presence of combined pulmonary fibrosis and emphysema

Background In the clinical management of patients with combined pulmonary fibrosis and emphysema (CPFE), early recognition and appropriate treatment is essential. This study was designed to develop an accurate prognostic nomogram model to predict the presence of CPFE. Methods We retrospectively enrolled 85 patients with CPFE and 128 patients with idiopathic pulmonary fibrosis (IPF) between January 2015 and January 2020. Clinical characteristics were compared between groups. A multivariable logistic regression analysis was performed to identify risk factors for CPFE. Then, and a nomogram to predict the presence of CPFE was constructed for clinical use. Concordance index (C-index), area under the receiver operating characteristic curve (AUC), and calibration plot was used to evaluate the efficiency of the nomogram. Results Compared to the IPF group, the proportion of patients with male, smoking and allergies were significantly higher in the CPFE group. In terms of pulmonary function tests, patients with CPFE had lower FEV1/FVC%, DLCO/VA% pred, and higher RV, RV%pred, VC, VC%pred, TLC%pred, VA, TLC, TLC%pred, FVC, FVC%pred and FEV1 with significant difference than the other group. Positive correlation was found between DLCO and VA%, RV%, TLC% in patients with IPF but not in patients with CPFE. By multivariate analysis, male, smoking, allergies, FEV1/FVC% and DLCO/VA%pred were identified as independent predictors of the presence of CPFE. The nomogram was then developed using these five variables. After 1000 internal validations of bootstrap resampling, the C-index of the nomogram was 0.863 (95% CI 0.795–0.931) and the AUC was 0.839 (95% CI 0.764–0.913). Moreover, the calibration plot showed good concordance of incidence of CPFE between nomogram prediction and actual observation (Hosmer–Lemeshow test: P = 0.307). Conclusions Patients of CPFE have a characteristic lung function profile including relatively preserved lung volumes and ventilating function, contrasting with a disproportionate reduction of carbon monoxide transfer. By incorporating clinical risk factors, we created a nomogram to predict the presence of CPFE, which may serve as a potential tool to guide personalized treatment.