The Importance, Challenges, and Possible Solutions for Sharing Proteomics Data While Safeguarding Individuals' Privacy.

Proteomics data sharing has profound benefits at the individual level as well as at the community level. While data sharing has increased over the years, mostly due to journal and funding agency requirements, the reluctance of researchers with regard to data sharing is evident as many shares only the bare minimum dataset required to publish an article. In many cases, proper metadata is missing, essentially making the dataset useless. This behavior can be explained by a lack of incentives, insufficient awareness, or a lack of clarity surrounding ethical issues. Through adequate training at research institutes, researchers can realize the benefits associated with data sharing and can accelerate the norm of data sharing for the field of proteomics, as has been the standard in genomics for decades. In this article, we have put together various repository options available for proteomics data. We have also added pros and cons of those repositories to facilitate researchers in selecting the repository most suitable for their data submission. It is also important to note that a few types of proteomics data have the potential to re-identify an individual in certain scenarios. In such cases, extra caution should be taken to remove any personal identifiers before sharing on public repositories. Data sets that will be useless without personal identifiers need to be shared in a controlled access repository so that only authorized researchers can access the data and personal identifiers are kept safe.

GlyComb: A novel glycoconjugate data repository that bridges glycomics and proteomics.

The glycosylation of proteins and lipids is known to be closely related to the mechanisms of various diseases such as influenza, cancer, and muscular dystrophy. Therefore, it has become clear that the analysis of post-translational modifications of proteins, including glycosylation, is important to accurately understand the functions of each protein molecule and the interactions among them. In order to conduct large-scale analyses more efficiently, it is essential to promote the accumulation, sharing, and reuse of experimental and analytical data in accordance with the FAIR (Findability, Accessibility, Interoperability, and Re-usability) data principles. However, a FAIR data repository for storing and sharing glycoconjugate information, including glycopeptides and glycoproteins, in a standardized format did not exist. Therefore, we have developed GlyComb (https://glycomb.glycosmos.org) as a new standardized data repository for glycoconjugate data. Currently, GlyComb can assign a unique identifier to a set of glycosylation information associated with a specific peptide sequence or UniProt ID. By standardizing glycoconjugate data via GlyComb identifiers and coordinating with existing web resources such as GlyTouCan and GlycoPOST, a comprehensive system for data submission and data sharing among researchers can be established. Here we introduce how GlyComb is able to integrate the variety of glycoconjugate data already registered in existing data repositories to obtain a better understanding of the available glycopeptides and glycoproteins, and their glycosylation patterns. We also explain how this system can serve as a foundation for a better understanding of glycan function.

CropMetabolome: a comprehensive metabolome database for major crops cross eight categories.

Chemical compositions of crops are of great agronomical importance, as crops serve as resources for nutrition, energy, and medicines for human and livestock. For crop metabolomics research, the lack of crop reference metabolome and high-quality reference compound mass spectra, as well as utilities for metabolic profiling, has hindered the discovery and functional study of phytochemicals in crops. To meet these challenging needs, we have developed the Crop Metabolome database (abbreviated as CropMetabolome) that is dedicated to the construction of crop reference metabolome, repository, and dissemination of crop metabolomic data, and profiling and analytic tools for metabolomics research. CropMetabolome contains a metabolomics database for more than 50 crops (belonging to eight categories) that integrated self-generated raw mass spectral data and public-source datasets. The reference metabolome for 59 crop species was constructed, which have functions that parallel those of reference genome in genomic studies. CropMetabolome also contains 'Standard compound mass spectral library', 'Flavonoids library', 'Pesticide library', and a set of related analytical tools that enable metabolic profiling based on a reference metabolome (CropRefMetaBlast), annotation and identification of new metabolites (CompoundLibBlast), deducing the structure of novel flavonoid derivatives (FlavoDiscover), and detecting possible residual pesticides in crop samples (PesticiDiscover). In addition, CropMetabolome is a repository to share and disseminate metabolomics data and a platform to promote collaborations to develop reference metabolome for more crop species. CropMetabolome is a comprehensive platform that offers important functions in crop metabolomics research and contributes to improve crop breeding, nutrition, and safety. CropMetabolome is freely available at https://www.cropmetabolome.com/.

Statewide Cancer Drug Repository Reducing Waste in the Setting of Shortage Crisis.

Disparities in cancer treatment, including access to medications, continue to exist. Rising drug prices and cancer drug shortages are 2 causes of inequitable access to treatment. This article introduces pilot outcomes for a solution to improve access to medications while also decreasing medication waste. Cancer drug repositories are an innovative patient-centered model where donations of unused cancer medications from patients are repurposed and provided to patients who are most vulnerable and disproportionately harmed by financial toxicity. This model demonstrates efficiency and sustainability that complements integrated care and provides an approach to increase medication access and decrease medication waste.

The mutant mouse resource and research center (MMRRC) consortium: the US-based public mouse repository system.

Now in its 25th year, the Mutant Mouse Resource and Research Center (MMRRC) consortium continues to serve the United States and international biomedical scientific community as a public repository and distribution archive of laboratory mouse models of human disease for research. Supported by the National Institutes of Health (NIH), the MMRRC consists of 4 regionally distributed and dedicated vivaria, offices, and specialized laboratory facilities and an Informatics Coordination and Service Center (ICSC). The overarching purpose of the MMRRC is to facilitate groundbreaking biomedical research by offering an extensive repertoire of mutant mice that are essential for advancing the understanding of human physiology and disease. The function of the MMRRC is to identify, acquire, evaluate, characterize, cryopreserve, and distribute mutant mouse strains to qualified biomedical investigators around the nation and the globe. Mouse strains accepted from the research community are held to the highest scientific standards to optimize reproducibility and enhance scientific rigor and transparency. All submitted strains are thoroughly reviewed, documented, and validated using extensive scientific quality control measures. In addition, the MMRRC conducts resource-related research on cryopreservation, mouse genetics, environmental conditions, and other topics that enhance operations of the MMRRC. Today, the MMRRC maintains an archive of mice, cryopreserved embryos and sperm, embryonic stem (ES) cell lines, and murine hybridomas for nearly 65,000 alleles. Since its inception, the MMRRC has fulfilled more than 20,000 orders from 13,651 scientists at 8441 institutions worldwide. The MMRRC also provides numerous services to assist researchers, including scientific consultation, technical assistance, genetic assays, microbiome analysis, analytical phenotyping, pathology, cryorecovery, husbandry, breeding and colony management, infectious disease surveillance, and disease modeling. The ICSC coordinates MMRRC operations, interacts with researchers, and manages the website (mmrrc.org) and online catalogue. Researchers benefit from an expansive list of well-defined mouse models of disease that meet the highest scientific standards while submitting investigators benefit by having their mouse strains cryopreserved, protected, and distributed in compliance with NIH policies.

Stability and Speciation of Hydrated Magnetite {111} Surfaces from Ab Initio Simulations with Relevance for Geochemical Redox Processes.

Magnetite is a common mixed Fe(II,III) iron oxide in mineral deposits and the product of (anaerobic) iron corrosion. In various Earth systems, magnetite surfaces participate in surface-mediated redox reactions. The reactivity and redox properties of the magnetite surface depend on the surface speciation, which varies with environmental conditions. In this study, Kohn-Sham density functional theory (DFT + U method) was used to examine the stability and speciation of the prevalent magnetite crystal face {111} in a wide range of pH and Eh conditions. The simulations reveal that the oxidation state and speciation of the surface depend strongly on imposed redox conditions and, in general, may differ from those of the bulk state. Corresponding predominant phase diagrams for the surface speciation and structure were calculated from first principles. Furthermore, classical molecular dynamics simulations were conducted investigating the mobility of water near the magnetite surface. The obtained knowledge of the surface structure and oxidation state of iron is essential for modeling retention of redox-sensitive nuclides.

Treatment modalities for infantile spasms: current considerations and evolving strategies in clinical practice.

Infantile spasms, newly classified as infantile epileptic spasm syndrome (IESS), occur in children under 2 years of age and present as an occur as brief, symmetrical, contractions of the musculature of the neck, trunk, and extremities. When infantile spasms occur with a concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression, it is known as West Syndrome. There is no universally accepted mainstay of treatment for this condition, but some options include synthetic adrenocorticotropic hormone (ACTH), repository corticotropin injection (RCI/Acthar Gel), corticosteroids, valproic acid, vigabatrin, and surgery. Without effective treatment, infantile spasms can cause an impairment of psychomotor development and/or cognitive and behavioral functions. The first-line treatment in the USA is ACTH related to high efficacy for cessation of infantile spasms long-term and low-cost profile. Acthar Gel is a repository corticotropin intramuscular injection that became FDA-approved for the treatment of IESS in 2010. Though it is believed that ACTH, Acthar Gel, and corticosteroids all work via a negative feedback pathway to decrease corticotropin-releasing hormone (CRH) release, their safety and efficacy profiles all vary. Vigabatrin and valproic acid are both anti-seizure medications that work by increasing GABA concentrations in the CNS and decreasing excitatory activity. Acthar Gel has been shown to have superior efficacy and a diminished side effect profile when compared with other treatment modalities.

Efficient Defect Detection of Rotating Goods under the Background of Intelligent Retail.

Dynamic visual vending machines are rapidly growing in popularity, offering convenience and speed to customers. However, there is a prevalent issue with consumers damaging goods and then returning them to the machine, severely affecting business interests. This paper addresses the issue from the standpoint of defect detection. Although existing industrial defect detection algorithms, such as PatchCore, perform well, they face challenges, including handling goods in various orientations, detection speeds that do not meet real-time monitoring requirements, and complex backgrounds that hinder detection accuracy. These challenges hinder their application in dynamic vending environments. It is crucial to note that efficient visual features play a vital role in memory banks, yet current memory repositories for industrial inspection algorithms do not adequately address the problem of location-specific feature redundancy. To tackle these issues, this paper introduces a novel defect detection algorithm for goods using adaptive subsampling and partitioned memory banks. Firstly, Grad-CAM is utilized to extract deep features, which, in combination with shallow features, mitigate the impact of complex backgrounds on detection accuracy. Next, graph convolutional networks extract rotationally invariant features. The adaptive subsampling partitioned memory bank is then employed to store features of non-defective goods, which reduces memory consumption and enhances training speed. Experimental results on the MVTec AD dataset demonstrate that the proposed algorithm achieves a marked improvement in detection speed while maintaining accuracy that is comparable to state-of-the-art models.

Searches as data: archiving and sharing search strategies using an institutional data repository.

Background: By defining search strategies and related database exports as code/scripts and data, librarians and information professionals can expand the mandate of research data management (RDM) infrastructure to include this work. This new initiative aimed to create a space in McGill University's institutional data repository for our librarians to deposit and share their search strategies for knowledge syntheses (KS). Case Presentation: The authors, a health sciences librarian and an RDM specialist, created a repository collection of librarian-authored knowledge synthesis (KS) searches in McGill University's Borealis Dataverse collection. We developed and hosted a half-day "Dataverse-a-thon" where we worked with a team of health sciences librarians to develop a standardized KS data management plan (DMP), search reporting documentation, Dataverse software training, and howto guidance for the repository. Conclusion: In addition to better documentation and tracking of KS searches at our institution, the KS Dataverse collection enables sharing of searches among colleagues with discoverable metadata fields for searching within deposited searches. While the initial creation of the DMP and documentation took about six hours, the subsequent deposit of search strategies into the institutional data repository requires minimal effort (e.g., 5-10 minutes on average per deposit). The Dataverse collection also empowers librarians to retain intellectual ownership over search strategies as valuable stand-alone research outputs and raise the visibility of their labor. Overall, institutional data repositories provide specific benefits in facilitating compliance both with PRISMA-S guidance and with RDM best practices.

Down Syndrome Biobank Consortium: A perspective.

Individuals with Down syndrome (DS) have a partial or complete trisomy of chromosome 21, resulting in an increased risk for early-onset Alzheimer's disease (AD)-type dementia by early midlife. Despite ongoing clinical trials to treat late-onset AD, individuals with DS are often excluded. Furthermore, timely diagnosis or management is often not available. Of the genetic causes of AD, people with DS represent the largest cohort. Currently, there is a knowledge gap regarding the underlying neurobiological mechanisms of DS-related AD (DS-AD), partly due to limited access to well-characterized brain tissue and biomaterials for research. To address this challenge, we created an international consortium of brain banks focused on collecting and disseminating brain tissue from persons with DS throughout their lifespan, named the Down Syndrome Biobank Consortium (DSBC) consisting of 11 biobanking sites located in Europe, India, and the USA. This perspective describes the DSBC harmonized protocols and tissue dissemination goals.

Dramatic loss of microbial viability in bentonite exposed to heat and gamma radiation: implications for deep geological repository.

Bentonite is an integral part of the engineered barrier system (EBS) in deep geological repositories (DGR) for nuclear waste, but its indigenous microorganisms may jeopardize long-term EBS integrity. To predict microbial activity in DGRs, it is essential to understand microbial reactions to the early hot phase of DGR evolution. Two bentonites (BCV and MX-80) with varied bentonite/water ratios and saturation levels (compacted to 1600 kg.m- 3 dry density/powder/suspension), were subjected to heat (90-150 °C) and irradiation (0.4 Gy.h- 1) in the long-term experiments (up to 18 months). Molecular-genetic, microscopic, and cultivation-based techniques assessed microbial survivability. Exposure to 90 °C and 150 °C notably diminished microbial viability, irrespective of bentonite form, with negligible impacts from irradiation or sample type compared to temperature. Bentonite powder samples exhibited microbial recovery after 90 °C heating for up to 6 months but not 12 months in most cases; exposure to 150 °C had an even stronger effect. Further long-term experiments at additional temperatures combined with the mathematical prediction of temperature evolution in DGR are recommended to validate the possible evolution and spatial distribution of microbially depleted zones in bentonite buffer around the waste canisters and refine predictions of microbial effects over time in the DGR.

Introducing BRAINOER: The Behavioral Research and Interdisciplinary Neuroscience Open Educational Repository.

Foundational textbooks for neuroscience courses can be cost-prohibitive for students and may omit recent advances in the field. Therefore, an Open Educational Resource (OER) repository was curated using existing OER materials for use in behavioral neuroscience and physiology courses. The Behavioral Research and Interdisciplinary Neuroscience Open Educational Repository (BRAINOER) contains 9 modules that include the following foundational topics: (1) The Brain and Nervous System, (2) Neurons, (3) The Endocrine System, (4) Neurotransmitters and Psychopharmacology, (5) Motor Processing, (6) Advanced Brain Functions, (7) Sensation and Perception, (8) Genetics and Evolution, (9) Research, Design, and Methods. Each module contains learning objectives in a checklist format, and modules are divided into basic and advanced content where appropriate. Because the repository is divided into content modules, the materials can be used as a full-curriculum or assigned on a module-by-module basis.

The metabolomics workbench file status website: a metadata repository promoting FAIR principles of metabolomics data.

BACKGROUND: An updated version of the mwtab Python package for programmatic access to the Metabolomics Workbench (MetabolomicsWB) data repository was released at the beginning of 2021. Along with updating the package to match the changes to MetabolomicsWB's 'mwTab' file format specification and enhancing the package's functionality, the included validation facilities were used to detect and catalog file inconsistencies and errors across all publicly available datasets in MetabolomicsWB. RESULTS: The MetabolomicsWB File Status website was developed to provide continuous validation of MetabolomicsWB data files and a useful interface to all found inconsistencies and errors. This list of detectable issues/errors include format parsing errors, format compliance issues, access problems via MetabolomicsWB's REST interface, and other small inconsistencies that can hinder reusability. The website uses the mwtab Python package to pull down and validate each available analysis file and then generates an html report. The website is updated on a weekly basis. Moreover, the Python website design utilizes GitHub and GitHub.io, providing an easy to replicate template for implementing other metadata, virtual, and meta- repositories. CONCLUSIONS: The MetabolomicsWB File Status website provides a metadata repository of validation metadata to promote the FAIR use of existing metabolomics datasets from the MetabolomicsWB data repository.

dbGaPCheckup: pre-submission checks of dbGaP-formatted subject phenotype files.

BACKGROUND: Data archiving and distribution are essential to scientific rigor and reproducibility of research. The National Center for Biotechnology Information's Database of Genotypes and Phenotypes (dbGaP) is a public repository for scientific data sharing. To support curation of thousands of complex data sets, dbGaP has detailed submission instructions that investigators must follow when archiving their data. RESULTS: We developed dbGaPCheckup, an R package which implements a series of check, awareness, reporting, and utility functions to support data integrity and proper formatting of the subject phenotype data set and data dictionary prior to dbGaP submission. For example, as a tool, dbGaPCheckup ensures that the data dictionary contains all fields required by dbGaP, and additional fields required by dbGaPCheckup; the number and names of variables match between the data set and data dictionary; there are no duplicated variable names or descriptions; observed data values are not more extreme than the logical minimum and maximum values stated in the data dictionary; and more. The package also includes functions that implement a series of minor/scalable fixes when errors are detected (e.g., a function to reorder the variables in the data dictionary to match the order listed in the data set). Finally, we also include reporting functions that produce graphical and textual descriptives of the data to further reduce the likelihood of data integrity issues. The dbGaPCheckup R package is available on CRAN ( https://CRAN.R-project.org/package=dbGaPCheckup ) and developed on GitHub ( https://github.com/lwheinsberg/dbGaPCheckup ). CONCLUSION: dbGaPCheckup is an innovative assistive and timesaving tool that fills an important gap for researchers by making dbGaP submission of large and complex data sets less error prone.

pandasGWAS: a Python package for easy retrieval of GWAS catalog data.

BACKGROUND: Since the NHGRI-EBI Catalog of human genome-wide association studies was established by NHGRI in 2008, research on it has attracted more and more researchers as the amount of data has grown rapidly. Easy-to-use, open-source, general-purpose programs for accessing the NHGRI-EBI Catalog of human genome-wide association studies are in great demand for current Python data analysis pipeline. RESULTS: In this work we present pandasGWAS, a Python package that provides programmatic access to the NHGRI-EBI Catalog of human genome-wide association studies. Instead of downloading all data locally, pandasGWAS queries data based on input criteria and handles paginated data gracefully. The data is then transformed into multiple associated pandas.DataFrame objects according to its hierarchical relationships, which makes it easy to integrate into current Python-based data analysis toolkits. CONCLUSIONS: pandasGWAS is an open-source Python package that provides the first Python client interface to the GWAS Catalog REST API. Compared with existing tools, the data structure of pandasGWAS is more consistent with the design specification of GWAS Catalog REST API, and provides many easy-to-use mathematical symbol operations.

Conserve the open media ecosystem! Legal and ethical considerations when using online repositories for AI training in ecological research.

Ecological researchers who train Artificial Intelligence models using digital media have to be cognizant of legal and ethical implications when sourcing such content from online repositories. The way forward? Complying with Creative Commons licensing requirements, obtaining consent from media creators and adhering to FAIR data principles. Collective action from researchers, repositories, licence providers, and legislators is needed to conserve this complex open media ecosystem. This way, we can continue to develop innovative applications to address pressing ecological issues while maintaining the trust of content creators and respecting the legal and ethical framework of online media use.

Transitioning from a research protocol to a scalable applied pathway for Xenopus laevis sperm cryopreservation at a national stock center: The effect of cryoprotectants.

Sperm cryopreservation is a critical tool for safeguarding and managing valuable genetic resources. Protocols for cryopreservation of Xenopus laevis sperm were available but lacking sperm quality evaluation and scalability and the outcomes were inconsistent. The goal of this study was to begin developing a center-level cryopreservation pathway for this species by integrating French straws as containers that would facilitate germplasm repository development. The objectives were to analyze the effect of: (1) three sperm concentrations (33, 50, and 100 × 106 sperm/mL) on post-thaw fertilization, (2) three final concentrations (2.5%, 5%, and 10%) of dimethyl sulfoxide, methanol, and dimethylformamide (DMFA) on sperm membrane integrity of fresh and frozen samples, (3) two concentrations (5% and 10%) of DMFA with and without 5% sucrose at four cooling rates (5, 10, 20, and 40°C/min) on sperm membrane integrity and motility, and (4) egg exposure to different concentrations of DMFA on fertilization. Few differences in sperm viability were found among fresh samples incubated in cryoprotectants, but thawed samples frozen in methanol or DMFA presented higher membrane integrity. Samples frozen in 10% DMFA at 20°C/min showed higher membrane integrity (60 ± 7%) than other DMFA concentrations and cooling rates, and the same total motility (30 ± 7%) as at 10°C/min. Higher DMFA concentrations (10%-13%) were detrimental for embryo development compared to lower concentrations (<6%). This study provided a reliable protocol for sperm cryopreservation in Xenopus laevis to yield an application pathway with potential for high throughput that can be used as a roadmap for work with other species.

Efficacy and safety of repository corticotropin injection for refractory cutaneous dermatomyositis: a prospective, open-label study.

OBJECTIVES: Cutaneous dermatomyositis (DM) is often refractory to multiple medications. Repository corticotropin injection (RCI) is FDA-approved for DM, but little is known about its efficacy and safety for treating cutaneous DM. We conducted a prospective, open-label trial assessing efficacy and safety of RCI for treating refractory cutaneous DM. METHODS: DM patients with moderate-to-severe cutaneous activity [Cutaneous Dermatomyositis Disease Area and Severity Index activity (CDASI-A)] >14 despite prior treatment with ≥2 systemic agents were enrolled. Patients were initiated on 80 u RCI twice weekly for 6 months. Primary outcomes included significant decreases in CDASI-A and Physician's Global Assessment (PGA) scores at 6 months. RESULTS: Of nineteen patients enrolled, fifteen patients (11 females, 4 males) with DM (7 classic, 8 amyopathic) completed 6 months of RCI treatment. Patients were treated with a median 3.0 systemic medications prior to enrolment and were taking a median of 2.0 systemic medications at enrolment. Median baseline CDASI-A score was 19.0 and median PGA activity score was 2.5/10. For patient-reported outcomes, baseline median patient global skin score (PtGSS) was 3.0/10 and median dermatology life quality index (DLQI) score was 7.0/10. At 6 months, there were statistically significant improvements in CDASI-A scores (median= 10.0), PGA scores (median= 0.8/10), PtGSS scores (median= 7.0) and DLQI scores (median= 2.0), among others. Adverse effects were mild. CONCLUSIONS: RCI treatment resulted in statistically significant and clinically meaningful improvement in cutaneous DM activity and quality of life. Our results suggest RCI is an effective, safe, and well-tolerated treatment for patients with refractory cutaneous dermatomyositis. CLINICAL TRIAL REGISTRATION: This clinical trial was registered with ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT01906372).

Efficacy of six exercise-based interventions for individuals undergoing hemodialysis: a network meta-analysis of randomized clinical trials.

BACKGROUND: Evidence comparing different exercise modalities in individuals undergoing hemodialysis remains incipient. Our aim was to conduct a systematic review and network meta-analysis of randomized clinical trials to compare and synthesize the efficacy of five different intradialytic exercise modalities and home-based training in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Studies were searched in PubMed/MEDLINE, Cochrane Library, Embase, Cinahl, and Scopus from their inception to 19 September 2022. We used traditional random-effects models and Bayesian network meta-analysis models. The risk of bias was assessed using the RoB v.2.0 tool, and the assessment of confidence in the results through the Confidence in Network Meta-Analysis (CINeMA) tool. RESULTS: Seventy-eight studies involving 3326 participants were included. Our network meta-analysis showed that combined training was the intervention with the best performance to increase VO2 peak [mean difference (MD) = 3.94 ml/kg/min; 95% credible interval (CrI), 2.38 to 5.76] and to reduce diastolic blood pressure (MD = -5.19 mmHg; 95%CrI, -9.35 to -0.96) compared to the usual care group. Inspiratory muscle training was the intervention that most improved the 6-minute walk test distance (MD = 70.97 m; 95%CrI, 18.09 to 129.87). C-reactive protein decreased in resistance training (MD = -2.6 mg/l; 95%CrI, -4.97 to -0.33) and aerobic training (MD = -1.4 mg/l; 95%CrI, -3.15 to -0.06). Kt/V improved in aerobic training (MD = 0.11; 95%CrI, 0.02 to 0.18), and SF-36 physical functioning outcomes improved in resistance training (MD = 10.66 points; 95%Crl, 1.91 to 20.22). No intradialytic exercise modality was superior to others or comparable with home-based training in improving the evaluated outcomes. Subgroup analysis revealed that exercise interventions >12 weeks improved functional capacity more than interventions ≤12 weeks, and that combined training reduces diastolic blood pressure only after 12 weeks of follow-up. Furthermore, our results suggest that moderate or moderate-to-vigorous intensity training leads to more pronounced improvements in functional capacity, whereas mild or mild-to-moderate intensity training does not have the same effect. In this review, most of the included studies were assessed as having some concern, which resulted in a low to very low level of confidence in the overall findings. CONCLUSIONS: Both intradialytic training and home-based training can promote benefits for individuals undergoing hemodialysis, with no evidence of the superiority of either training modality over the other.

Genetic and evolutionary dissection of melatonin response signaling facilitates the regulation of plant growth and stress responses.

The expansion of gene families during evolution could generate functional diversity among their members to regulate plant growth and development. Melatonin, a phylogenetically ancient molecule, is vital for many aspects of a plant's life. Understanding the functional diversity of the molecular players involved in melatonin biosynthesis, signaling, and metabolism will facilitate the regulation of plant phenotypes. However, the molecular mechanism of melatonin response signaling elements in regulating this network still has many challenges. Here, we provide an in-depth analysis of the functional diversity and evolution of molecular components in melatonin signaling pathway. Genetic analysis of multiple mutants in plant species will shed light on the role of gene families in melatonin regulatory pathways. Phylogenetic analysis of these genes was performed, which will facilitate the identification of melatonin-related genes for future study. Based on the abovementioned signal networks, the mechanism of these genes was summarized to provide reference for studying the regulatory mechanism of melatonin in plant phenotypes. We hope that this work will facilitate melatonin research in higher plants and finely tuned spatio-temporal regulation of melatonin signaling.