Performance assessment of a 125 human plasma peptide mixture stored at room temperature for multiple reaction monitoring-mass spectrometry

Synthetic peptides are a critical requirement for the development and application of targeted mass spectrometry (MS)-based assays for the quantitation of proteins from biological matrices. Transporting synthetic peptides on dry ice from one laboratory to another is costly and often difficult because of country-specific import and export regulations. Therefore, in this study, we assessed the impact of leaving a lyophilized mixture consisting of 125 peptides at room temperature for up to 20 days, and we assessed the effect on the quantitative performance of multiple reaction monitoring-MS (MRM-MS) assays. The findings suggest that there are no significant differences in the MRM-MS results for the time points assessed in this study (up to 20 days). All the calibration curves and quality control (QC) samples met the acceptance criteria for precision and accuracy (raw data are available via the public MS data repository PanoramaWeb, identifier: /MRM Proteomics/2020_BAK125_RT). The number of endogenous proteins quantifiable across five plasma samples was consistently between 87 and 99 out of 125 for all time points. Moreover, the coefficients of variation (CVs) calculated for the majority of peptide concentrations across all samples and time points were <5%. In addition, a lyophilized peptide mixture was transported from Canada to Iceland without dry ice. The results showed that there was no significant difference in the quantitative performance, with the determined concentrations of most proteins in the samples falling within 30% between the analyses performed on the same three plasma samples in Iceland and those in Canada. Overall, a comparison of the results obtained in Canada and in Iceland indicated that the peptides were stable under the conditions tested and also indicated that shipping lyophilized peptide mixtures without dry ice, but in the presence of sufficient desiccant material, could be a feasible option in cases where transport difficulties may arise or dry-ice sublimation may occur.Proteomic

Systematic Review and Meta-Analysis: An Empirical Approach to Defining Treatment Response and Remission in Pediatric Obsessive-Compulsive Disorder

©. This manuscript version is made available under the CC-BY-NC 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the, Submitted, version of a Published Work that appeared in final form in Journal of the American Academy of Child and Adolescent Psychiatry. To access the final edited and published work see: https://doi.org/10.1016/j.jaac.2021.05.027Objective: A lack of universal definitions for response and remission in pediatric obsessive- compulsive disorder (OCD) has hampered the comparability of results across trials. To address this problem, we conducted an individual participant data diagnostic test accuracy meta-analysis to evaluate the discriminative ability of the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) in determining response and remission. We also aimed to generate empirically derived cutoffs on the CY-BOCS for these outcomes. Method: A systematic review of PubMed, PsycINFO, Embase and CENTRAL identified 5,401 references, 42 randomized controlled clinical trials (RCTs) were considered eligible and 21 provided data for inclusion (N 1,234). A score ≤ 2 in the Clinical Global Impressions Improvement and Severity scales were chosen to define response and remission, respectively. A two-stage random-effects meta-analysis model was established. The area under the curve (AUC) and the Youden Index were computed to indicate the discriminative ability of the CY-BOCS and to guide for the optimal cutoff, respectively. Results: The CY-BOCS had sufficient discriminative ability to determine response (AUC 0.89) and remission (AUC 0.92). The optimal cutoff for response was a ≥ 35% reduction from baseline to posttreatment (sensitivity [95% CI] 83.9 [83.7, 84.1]; specificity [95% CI] 81.7 [81.5, 81.9]). The optimal cutoff for remission was a posttreatment raw score ≤ 12 (sensitivity [95% CI] 82.0 [81.8, 82.2]; specificity [95% CI] 84.6 [84.4, 84.8]). Conclusion: Meta-analysis identified empirically optimal cutoffs on the CY-BOCS to determine response and remission in pediatric OCD RCTs. Systematic adoption of standardized operational definitions for response and remission will improve comparability across trials for pediatric OCD

A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPreviously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.info:eu-repo/grantAgreement/EC/FP7/21807

The Nordic long-term OCD treatment study (NordLOTS): rationale, design, and methods

BACKGROUND: This paper describes and discusses the methodology of the Nordic long-term OCD-treatment study (NordLOTS). The purpose of this effectiveness study was to study treatment outcome of CBT, to identify CBT non- or partial responders and to investigate whether an increased number of CBT-sessions or sertraline treatment gives the best outcome; to identify treatment refractory patients and to investigate the outcome of aripiprazole augmentation; to study the outcome over a three year period for each responder including the risk of relapse, and finally to study predictors, moderators and mediators of treatment response. METHODS: Step 1 was an open and uncontrolled clinical trial with CBT, step 2 was a controlled, randomised non-blinded study of CBT non-responders from step 1. Patients were randomized to receive either sertraline plus CBT-support or continued and modified CBT. In step 3 patients who did not respond to either CBT or sertraline were treated with aripiprazole augmentation to sertraline. CONCLUSIONS: This multicenter trial covering three Scandinavian countries is going to be the largest CBT-study for paediatric OCD to date. It is not funded by industry and tries in the short and long-term to answer the question whether further CBT or SSRI is better in CBT non-responders

The Nordic long-term OCD treatment study (NordLOTS): rationale, design, and methods

-BACKGROUND: This paper describes and discusses the methodology of the Nordic long-term OCD-treatment study (NordLOTS). The purpose of this effectiveness study was to study treatment outcome of CBT, to identify CBT non- or partial responders and to investigate whether an increased number of CBT-sessions or sertraline treatment gives the best outcome; to identify treatment refractory patients and to investigate the outcome of aripiprazole augmentation; to study the outcome over a three year period for each responder including the risk of relapse, and finally to study predictors, moderators and mediators of treatment response. METHODS: Step 1 was an open and uncontrolled clinical trial with CBT, step 2 was a controlled, randomised non-blinded study of CBT non-responders from step 1. Patients were randomized to receive either sertraline plus CBT-support or continued and modified CBT. In step 3 patients who did not respond to either CBT or sertraline were treated with aripiprazole augmentation to sertraline. CONCLUSIONS: This multicenter trial covering three Scandinavian countries is going to be the largest CBT-study for paediatric OCD to date. It is not funded by industry and tries in the short and long-term to answer the question whether further CBT or SSRI is better in CBT non-responders.© 2013 Thomsen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated