Frontiers in aging最新文献

{"title":"Understanding human aging and the fundamental cell signaling link in age-related diseases: the middle-aging hypovascularity hypoxia hypothesis.","authors":"Teow J Phua","doi":"10.3389/fragi.2023.1196648","DOIUrl":"10.3389/fragi.2023.1196648","url":null,"abstract":"<p><p>Aging-related hypoxia, oxidative stress, and inflammation pathophysiology are closely associated with human age-related carcinogenesis and chronic diseases. However, the connection between hypoxia and hormonal cell signaling pathways is unclear, but such human age-related comorbid diseases do coincide with the middle-aging period of declining sex hormonal signaling. This scoping review evaluates the relevant interdisciplinary evidence to assess the systems biology of function, regulation, and homeostasis in order to discern and decipher the etiology of the connection between hypoxia and hormonal signaling in human age-related comorbid diseases. The hypothesis charts the accumulating evidence to support the development of a hypoxic milieu and oxidative stress-inflammation pathophysiology in middle-aged individuals, as well as the induction of amyloidosis, autophagy, and epithelial-to-mesenchymal transition in aging-related degeneration. Taken together, this new approach and strategy can provide the clarity of concepts and patterns to determine the causes of declining vascularity hemodynamics (blood flow) and physiological oxygenation perfusion (oxygen bioavailability) in relation to oxygen homeostasis and vascularity that cause hypoxia (hypovascularity hypoxia). The middle-aging hypovascularity hypoxia hypothesis could provide the mechanistic interface connecting the endocrine, nitric oxide, and oxygen homeostasis signaling that is closely linked to the progressive conditions of degenerative hypertrophy, atrophy, fibrosis, and neoplasm. An in-depth understanding of these intrinsic biological processes of the developing middle-aged hypoxia could provide potential new strategies for time-dependent therapies in maintaining healthspan for healthy lifestyle aging, medical cost savings, and health system sustainability.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10293850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9792487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic deletion of Kvβ2 (AKR6) causes loss of muscle function and increased inflammation in mice.","authors":"Ravikumar Manickam, Jazmine Virzi, Anish Potti, Feng Cheng, David W Russ, Srinivas M Tipparaju","doi":"10.3389/fragi.2023.1175510","DOIUrl":"10.3389/fragi.2023.1175510","url":null,"abstract":"<p><p>The voltage-gated potassium channels (Kv) are complex ion channels with distinct roles in neurotransmission, electrical conductivity of the heart, and smooth and striated muscle functions. Previously, we demonstrated that deletion of Kvβ2 in mice results in decreased Pax7 protein levels, hindlimb muscles and body weights, and fiber type switching. In the present study, we tested the hypothesis that Kvβ2 regulates skeletal muscle function in mice. The young and old Kvβ2 knockout (KO) and wildtype (WT) mice were utilized to test the aging phenotype and skeletal muscle function. Consistent with our previous finding, we found a significant reduction in hindlimb skeletal muscles mass and body weight in young Kvβ2 KO mice, which was also significantly reduced in old Kvβ2 KO mice compared with age-matched WT mice. Forelimb grip strength, and the hindleg extensor digitorum longus (EDL) muscles force-frequency relations were significantly decreased in young and old Kvβ2 KO mice compared to age-matched WT mice. Analysis of transmission electron microscopy images of EDL muscles in young mice revealed a significant reduction in the sarcomere length for Kvβ2 KO vs. WT. Hematoxylin and eosin-stained tibialis anterior muscles cryosections displayed a significant decrease in the number of medium (2,000-4,000 µm²) and largest (>4,000 µm²) myofibers area in young Kvβ2 KO vs. WT mice. We also found a significant increase in fibrotic tissue area in young Kvβ2 KO mice compared with age-matched WT mice. Analysis of RNA Seq data of the gastrocnemius muscles (GAS) identified significant increase in genes involved in skeletal muscle development, proliferation and cell fate determination, atrophy, energy metabolism, muscle plasticity, inflammation, and a decrease in circadian core clock genes in young Kvβ2 KO vs. WT mice. Several genes were significantly upregulated (384 genes) and downregulated (40 genes) in young Kvβ2 KO mice compared to age-matched WT mice. Further, RT-qPCR analysis of the GAS muscles displayed a significant increase in pro-inflammatory marker Il6 expression in young Kvβ2 KO mice compared to age-matched WT mice. Overall, the present study shows that deletion of Kvβ2 leads to decreased muscles strength and increased inflammation.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10292803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9717589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highlighting the value of Alzheimer's disease-focused registries: lessons learned from cancer surveillance.","authors":"Margaret C Miller,&nbsp;Rana Bayakly,&nbsp;Bernard G Schreurs,&nbsp;Kimberly J Flicker,&nbsp;Swann Arp Adams,&nbsp;Lucy A Ingram,&nbsp;James W Hardin,&nbsp;Matthew Lohman,&nbsp;Marvella E Ford,&nbsp;Quentin McCollum,&nbsp;Audrey McCrary-Quarles,&nbsp;Oluwole Ariyo,&nbsp;Sue E Levkoff,&nbsp;Daniela B Friedman","doi":"10.3389/fragi.2023.1179275","DOIUrl":"10.3389/fragi.2023.1179275","url":null,"abstract":"<p><p>Like cancer, Alzheimer's disease and related dementias (ADRD) comprise a global health burden that can benefit tremendously from the power of disease registry data. With an aging population, the incidence, treatment, and mortality from ADRD is increasing and changing rapidly. In the same way that current cancer registries work toward prevention and control, so do ADRD registries. ADRD registries maintain a comprehensive and accurate registry of ADRD within their state, provide disease prevalence estimates to enable better planning for social and medical services, identify differences in disease prevalence among demographic groups, help those who care for individuals with ADRD, and foster research into risk factors for ADRD. ADRD registries offer a unique opportunity to conduct high-impact, scientifically rigorous research efficiently. As research on and development of ADRD treatments continue to be a priority, such registries can be powerful tools for conducting observational studies of the disease. This perspectives piece examines how established cancer registries can inform ADRD registries' impact on public health surveillance, research, and intervention, and inform and engage policymakers.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9504254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin mitigates SASP secretion and LPS-triggered hyper-inflammation in Doxorubicin-induced senescent endothelial cells.","authors":"Ibrahim Y Abdelgawad, Kevin Agostinucci, Bushra Sadaf, Marianne K O Grant, Beshay N Zordoky","doi":"10.3389/fragi.2023.1170434","DOIUrl":"10.3389/fragi.2023.1170434","url":null,"abstract":"<p><p><b>Introduction:</b> Doxorubicin (DOX), a chemotherapeutic drug, induces senescence and increases the secretion of senescence-associated secretory phenotype (SASP) in endothelial cells (ECs), which contributes to DOX-induced inflammaging. Metformin, an anti-diabetic drug, demonstrates senomorphic effects on different models of senescence. However, the effects of metformin on DOX-induced endothelial senescence have not been reported before. Senescent ECs exhibit a hyper-inflammatory response to lipopolysachharide (LPS). Therefore, in our current work, we identified the effects of metformin on DOX-induced endothelial senescence and LPS-induced hyper-inflammation in senescent ECs. <b>Methods:</b> ECs were treated with DOX ± metformin for 24 h followed by 72 h incubation without DOX to establish senescence. Effects of metformin on senescence markers expression, SA-β-gal activity, and SASP secretion were assessed. To delineate the molecular mechanisms, the effects of metformin on major signaling pathways were determined. The effect of LPS ± metformin was determined by stimulating both senescent and non-senescent ECs with LPS for an additional 24 h. <b>Results:</b> Metformin corrected DOX-induced upregulation of senescence markers and decreased the secretion of SASP factors and adhesion molecules. These effects were associated with a significant inhibition of the JNK and NF-κB pathway. A significant hyper-inflammatory response to LPS was observed in DOX-induced senescent ECs compared to non-senescent ECs. Metformin blunted LPS-induced upregulation of pro-inflammatory SASP factors. <b>Conclusion:</b> Our study demonstrates that metformin mitigates DOX-induced endothelial senescence phenotype and ameliorates the hyper-inflammatory response to LPS. These findings suggest that metformin may protect against DOX-induced vascular aging and endothelial dysfunction and ameliorate infection-induced hyper-inflammation in DOX-treated cancer survivors.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variant biomarker discovery using mass spectrometry-based proteogenomics.","authors":"Luke Reilly, Sahba Seddighi, Andrew B Singleton, Mark R Cookson, Michael E Ward, Yue A Qi","doi":"10.3389/fragi.2023.1191993","DOIUrl":"10.3389/fragi.2023.1191993","url":null,"abstract":"<p><p>Genomic diversity plays critical roles in risk of disease pathogenesis and diagnosis. While genomic variants-including single nucleotide variants, frameshift variants, and mis-splicing isoforms-are commonly detected at the DNA or RNA level, their translated variant protein or polypeptide products are ultimately the functional units of the associated disease. These products are often released in biofluids and could be leveraged for clinical diagnosis and patient stratification. Recent emergence of integrated analysis of genomics with mass spectrometry-based proteomics for biomarker discovery, also known as proteogenomics, have significantly advanced the understanding disease risk variants, precise medicine, and biomarker discovery. In this review, we discuss variant proteins in the context of cancers and neurodegenerative diseases, outline current and emerging proteogenomic approaches for biomarker discovery, and provide a comprehensive proteogenomic strategy for detection of putative biomarker candidates in human biospecimens. This strategy can be implemented for proteogenomic studies in any field of enquiry. Our review timely addresses the need of biomarkers for aging related diseases.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher thyroid hormone has a negative association with lower limb lean body mass in euthyroid older adults: Analysis from the Baltimore Longitudinal study of aging.","authors":"Hamza Ahmed Ibad, Jennifer S Mammen, Eleanor M Simonsick, C Kent Kwoh, Ali Guermazi, Shadpour Demehri","doi":"10.3389/fragi.2023.1150645","DOIUrl":"10.3389/fragi.2023.1150645","url":null,"abstract":"<p><p><b>Background:</b> Hyperthyroidism is associated with lower lean body mass, as a result of catabolic actions of thyroid hormone. Therefore, higher thyroid hormone levels could be a factor in the development of sarcopenia and age associated functional decline. The relationship between thyroid hormone and muscle mass in ambulatory, euthyroid older adults is not known. <b>Method:</b> We used mixed-effects models to estimate the cross-sectional relationships (accounting for inter-person variability) between thyroid axis hormone measures and lower limb composition or sarcopenia at visits in the Baltimore Longitudinal Study of Aging (BLSA) at which DEXA scans were available and both thyrotropin (TSH) and free thyroxine (FT4) were in the reference range. Analyses were adjusted for levothyroxine use, age, race, sex, BMI, smoking, alcohol intake, cholesterol, and systolic blood pressure. <b>Results:</b> 1442 euthyroid participants (median age 68, 50% female, and 69% white) contributed to 5306 visits from 2003 to 2019. FT4 was negatively associated with lower limb lean mass (beta: 88.49; 95% Confidence Interval (CI): 122.78, -54.20; <i>p</i> < 0.001) and positively associated with sarcopenia (OR: 1.11%, 95% CI: 1.01, 1.22) in the whole cohort. Additionally, higher FT4 was associated with lower leg lean mass (beta: 66.79; 95% CI: 102.24, -31.33; <i>p</i> < 0.001) and sarcopenia (OR:1.09%, 95% CI:1.01, 1.18) in older adults, but not in younger adults alone. <b>Conclusion:</b> In euthyroid older adults, higher FT4 is associated with lower leg lean mass and higher odds of sarcopenia. Understanding the relationship between thyroid hormone and sarcopenia is needed to improve clinical decision-making and avoid functional decline from excess thyroid hormone use in older adults.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10126399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9772322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prioritizing research on over-the-counter (OTC) hearing aids for age-related hearing loss.","authors":"Vinaya Manchaiah, De Wet Swanepoel, Anu Sharma","doi":"10.3389/fragi.2023.1105879","DOIUrl":"10.3389/fragi.2023.1105879","url":null,"abstract":"<p><p>Hearing aids are the most commonly used treatment for people with age-related hearing loss, however, hearing aid uptake is low, primarily due to high cost of the device, stigma, and a lack of perceived need. To address accessibility and affordability issues, the U.S. Food and Drug Administration created a new over-the-counter (OTC) hearing aid category. Various types of hearing devices are available for both individuals with hearing loss and for those with normal hearing, as hearing enhancement devices. Hearing aids (i.e., prescription hearing aids, self-fitting OTC hearing aids, and pre-set OTC hearing aids) are regulated by the FDA. The purpose of this article is to (a) provide a summary of existing research on direct-to-consumer (DTC) hearing devices such as Personal Sound Amplification Products (PSAPs) that informs OTC service delivery models; (b) provide an update on existing and ongoing randomized controlled trials on currently marketed OTC hearing aids; and (c) highlight the need for immediate research on OTC hearing aids and service delivery models to inform policy and clinical care. It remains to be seen what effect OTC hearing aids have on improving the uptake of hearing aids by individuals with mild-to-moderate hearing loss. However, there is scant research on all aspects of OTC hearing aids that are currently on the market. We conclude that high quality independent research must be prioritized to supplement evidence provided by the OTC hearing aid manufacturers for regulatory approval purposes.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10078955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9326033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The RNA-Seq data analysis shows how the ontogenesis defines aging.","authors":"Lev Salnikov, Saveli Goldberg, Heena Rijhwani, Yuran Shi, Eugene Pinsky","doi":"10.3389/fragi.2023.1143334","DOIUrl":"10.3389/fragi.2023.1143334","url":null,"abstract":"<p><p>This paper presents a global statistical analysis of the RNA-Seq results of the entire <i>Mus musculus</i> genome. We explain aging by a gradual redistribution of limited resources between two major tasks of the organism: its self-sustenance based on the function of the housekeeping gene group (HG) and functional differentiation provided by the integrative gene group (IntG). All known disorders associated with aging are the result of a deficiency in the repair processes provided by the cellular infrastructure. Understanding exactly how this deficiency arises is our primary goal. Analysis of RNA production data of 35,630 genes, from which 5,101 were identified as HG genes, showed that RNA production levels in the HG and IntG genes had statistically significant differences (<i>p</i>-value <0.0001) throughout the entire observation period. In the reproductive period of life, which has the lowest actual mortality risk for <i>Mus musculus</i>, changes in the age dynamics of RNA production occur. The statistically significant dynamics of the decrease of RNA production in the HG group in contrast to the IntG group was determined (<i>p</i>-value = 0.0045). The trend toward significant shift in the HG/IntG ratio occurs after the end of the reproductive period, coinciding with the beginning of the mortality rate increase in <i>Mus musculus</i> indirectly supports our hypothesis. The results demonstrate a different orientation of the impact of ontogenesis regulatory mechanisms on the groups of genes representing cell infrastructures and their organismal functions, making the chosen direction promising for further research and understanding the mechanisms of aging.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9578239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards AI-driven longevity research: An overview.","authors":"Nicola Marino, Guido Putignano, Simone Cappilli, Emmanuele Chersoni, Antonella Santuccione, Giuliana Calabrese, Evelyne Bischof, Quentin Vanhaelen, Alex Zhavoronkov, Bryan Scarano, Alessandro D Mazzotta, Enrico Santus","doi":"10.3389/fragi.2023.1057204","DOIUrl":"10.3389/fragi.2023.1057204","url":null,"abstract":"<p><p>While in the past technology has mostly been utilized to store information about the structural configuration of proteins and molecules for research and medical purposes, Artificial Intelligence is nowadays able to learn from the existing data how to predict and model properties and interactions, revealing important knowledge about complex biological processes, such as aging. Modern technologies, moreover, can rely on a broader set of information, including those derived from the next-generation sequencing (e.g., proteomics, lipidomics, and other omics), to understand the interactions between human body and the external environment. This is especially relevant as external factors have been shown to have a key role in aging. As the field of computational systems biology keeps improving and new biomarkers of aging are being developed, artificial intelligence promises to become a major ally of aging research.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9199545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Markers of aging: Unsupervised integrated analyses of the human plasma proteome.","authors":"L Coenen, B Lehallier, H E de Vries, J Middeldorp","doi":"10.3389/fragi.2023.1112109","DOIUrl":"10.3389/fragi.2023.1112109","url":null,"abstract":"<p><p>Aging associates with an increased susceptibility for disease and decreased quality of life. To date, processes underlying aging are still not well understood, leading to limited interventions with unknown mechanisms to promote healthy aging. Previous research suggests that changes in the blood proteome are reflective of age-associated phenotypes such as frailty. Moreover, experimentally induced changes in the blood proteome composition can accelerate or decelerate underlying aging processes. The aim of this study is to identify a set of proteins in the human plasma associated with aging by integration of the data of four independent, large-scaled datasets using the aptamer-based SomaScan platform on the human aging plasma proteome. Using this approach, we identified a set of 273 plasma proteins significantly associated with aging (aging proteins, APs) across these cohorts consisting of healthy individuals and individuals with comorbidities and highlight their biological functions. We validated the age-associated effects in an independent study using a centenarian population, showing highly concordant effects. Our results suggest that APs are more associated to diseases than other plasma proteins. Plasma levels of APs can predict chronological age, and a reduced selection of 15 APs can still predict individuals' age accurately, highlighting their potential as biomarkers of aging processes. Furthermore, we show that individuals presenting accelerated or decelerated aging based on their plasma proteome, respectively have a more aged or younger systemic environment. These results provide novel insights in the understanding of the aging process and its underlying mechanisms and highlight potential modulators contributing to healthy aging.</p>","PeriodicalId":73061,"journal":{"name":"Frontiers in aging","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9157300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}