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      Sex and age-dependent characterization of the circadian clock as a potential biomarker for physical performance: A prospective study protocol

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          Abstract

          Introduction

          Circadian rhythms (CR) regulate daily cycles in behavior, physiology and molecular processes. CRs are endogenous and vary across individuals. Seasonal changes can influence CR. Accordingly, rhythms with different characteristics (amplitude, phase) are depicted during the summer months, as compared to winter. Increasing evidence points to an influence of circadian regulation on physical performance. Here, we aim to obtain a comprehensive circadian gene expression profile for physically active individuals, which can potentially be used for the identification of optimal time intervals for physical exercise.

          Methods and analysis

          To explore these different aspects, we propose a study where we will carry out a molecular analysis of CR by measuring the expression of specific clock and clock-controlled genes, based on a non-invasive approach using RNA extracted from saliva in physically active, healthy participants. We will collect data across two seasons and use computational algorithms to integrate the molecular data with hormonal data (cortisol and melatonin), and generate a profile of CR in healthy individuals of different sex and age groups. Finally, we will use computational tools to predict optimal time intervals for physical performance based on the above-described data, thereby retrieving valuable data on the circadian clock as a key factor for health maintenance and optimization.

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          Most cited references62

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          Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support.

          Research electronic data capture (REDCap) is a novel workflow methodology and software solution designed for rapid development and deployment of electronic data capture tools to support clinical and translational research. We present: (1) a brief description of the REDCap metadata-driven software toolset; (2) detail concerning the capture and use of study-related metadata from scientific research teams; (3) measures of impact for REDCap; (4) details concerning a consortium network of domestic and international institutions collaborating on the project; and (5) strengths and limitations of the REDCap system. REDCap is currently supporting 286 translational research projects in a growing collaborative network including 27 active partner institutions.
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            The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research

            Despite the prevalence of sleep complaints among psychiatric patients, few questionnaires have been specifically designed to measure sleep quality in clinical populations. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period with "good" sleepers (healthy subjects, n = 52) and "poor" sleepers (depressed patients, n = 54; sleep-disorder patients, n = 62). Acceptable measures of internal homogeneity, consistency (test-retest reliability), and validity were obtained. A global PSQI score greater than 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p less than 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.
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              A circadian gene expression atlas in mammals: implications for biology and medicine.

              To characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional "rush hours" preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spliceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy.
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                Author and article information

                Contributors
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                24 October 2023
                2023
                : 18
                : 10
                : e0293226
                Affiliations
                [1 ] Institute for Theoretical Biology (ITB), Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
                [2 ] Institute for Systems Medicine and Faculty of Human Medicine, MSH Medical School Hamburg, Hamburg, Germany
                Federal University of Rio Grande do Sul: Universidade Federal do Rio Grande do Sul, BRAZIL
                Author notes

                Competing Interests: A.R. has filled patents (PCT/EP2021/073798 and PCT/EP2021/073802) related to biomarkers for detecting the clock. M.Y. declares no financial or non-financial competing interests. The funders had no role in the design of the study or writing of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. “

                Author information
                https://orcid.org/0000-0002-9165-2439
                Article
                PONE-D-23-21529
                10.1371/journal.pone.0293226
                10597486
                37874792
                af758a65-22e2-4809-9060-ef92d82f812d
                © 2023 Yalçin, Relógio

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 16 July 2023
                : 4 October 2023
                Page count
                Figures: 2, Tables: 0, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100020027, Dr. Rolf M. Schwiete Stiftung;
                Award ID: 07/2019
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100017268, Berlin Institute of Health;
                Award Recipient :
                Funded by: Berlin School of Integrative Oncology (BSIO)
                Award Recipient :
                The work in the group of A.R. was funded by Rolf M. Schwiete Stiftung (07/2019), this study was additionally funded by the Digital Health Accelerator Program of the Berlin Institute for Health (BIH), grant to A.R.. M.Y was additionally funded by the Berlin School of Integrative Oncology (BSIO) graduate program of Charité—Universitätsmedizin Berlin funded within the German Excellence Initiative, and the German Cancer Consortium (GCC). Funding sources had no role in study design, interpretation, or writing of this report.
                Categories
                Study Protocol
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Saliva
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Saliva
                Biology and Life Sciences
                Physiology
                Body Fluids
                Saliva
                Biology and Life Sciences
                Genetics
                Gene Expression
                Biology and Life Sciences
                Chronobiology
                Circadian Rhythms
                Biology and Life Sciences
                Biochemistry
                Circadian Oscillators
                Biology and Life Sciences
                Chronobiology
                Circadian Oscillators
                Biology and Life Sciences
                Chronobiology
                Biology and Life Sciences
                Biochemistry
                Hormones
                Melatonin
                Biology and Life Sciences
                Biochemistry
                Hormones
                Lipid Hormones
                Cortisol
                Biology and Life Sciences
                Biochemistry
                Hormones
                Steroid Hormones
                Cortisol
                Earth Sciences
                Seasons
                Spring
                Custom metadata
                Deidentified research data will be made publicly available when the study is completed and published.

                Uncategorized
                Uncategorized

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