NPJ Parkinson's Disease最新文献

{"title":"Uric acid and alterations of purine recycling disorders in Parkinson’s disease: a cross-sectional study","authors":"Sayuri Shima, Yasuaki Mizutani, Junichiro Yoshimoto, Yasuhiro Maeda, Reiko Ohdake, Ryunosuke Nagao, Toshiki Maeda, Atsuhiro Higashi, Akihiro Ueda, Mizuki Ito, Tatsuro Mutoh, Hirohisa Watanabe","doi":"10.1038/s41531-024-00785-0","DOIUrl":"https://doi.org/10.1038/s41531-024-00785-0","url":null,"abstract":"<p>The relationship between reduced serum uric acid (UA) levels and Parkinson’s disease (PD), particularly purine metabolic pathways, is not fully understood. Our study compared serum and cerebrospinal fluid (CSF) levels of inosine, hypoxanthine, xanthine, and UA in PD patients and healthy controls. We analyzed 132 samples (serum, 45 PD, and 29 age- and sex-matched healthy controls; CSF, 39 PD, and 19 age- and sex-matched healthy controls) using liquid chromatography-tandem mass spectrometry. Results showed significantly lower serum and CSF UA levels in PD patients than in controls (<i>p</i> &lt; 0.0001; effect size <i>r</i> = 0.5007 in serum, <i>p</i> = 0.0046; <i>r</i> = 0.3720 in CSF). Decreased serum hypoxanthine levels were observed (<i>p</i> = 0.0002; <i>r</i> = 0.4338) in PD patients compared to controls with decreased CSF inosine and hypoxanthine levels (<i>p</i> &lt; 0.0001, <i>r</i> = 0.5396: <i>p</i> = 0.0276, <i>r</i> = 0.2893). A general linear model analysis indicated that the reduced UA levels were mainly due to external factors such as sex and weight in serum and age and weight in CSF unrelated to the purine metabolic pathway. Our findings highlight that decreased UA levels in PD are influenced by factors beyond purine metabolism, including external factors such as sex, weight, and age, emphasizing the need for further research into the underlying mechanisms and potential therapeutic approaches.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"40 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying potential causal effects of Parkinson’s disease: A polygenic risk score-based phenome-wide association and mendelian randomization study in UK Biobank","authors":"Changhe Shi, Dongrui Ma, Mengjie Li, Zhiyun Wang, Chenwei Hao, Yuanyuan Liang, Yanmei Feng, Zhengwei Hu, Xiaoyan Hao, Mengnan Guo, Shuangjie Li, Chunyan Zuo, Yuemeng Sun, Mibo Tang, Chengyuan Mao, Chan Zhang, Yuming Xu, Shilei Sun","doi":"10.1038/s41531-024-00780-5","DOIUrl":"https://doi.org/10.1038/s41531-024-00780-5","url":null,"abstract":"<p>There is considerable uncertainty regarding the associations between various risk factors and Parkinson’s Disease (PD). This study systematically screened and validated a wide range of potential PD risk factors from 502,364 participants in the UK Biobank. Baseline data for 1851 factors across 11 categories were analyzed through a phenome-wide association study (PheWAS). Polygenic risk scores (PRS) for PD were used to diagnose Parkinson’s Disease and identify factors associated with PD diagnosis through PheWAS. Two-sample Mendelian randomization (MR) analysis was employed to assess causal relationships. PheWAS results revealed 267 risk factors significantly associated with PD-PRS among the 1851 factors, and of these, 27 factors showed causal evidence from MR analysis. Compelling evidence suggests that fluid intelligence score, age at first sexual intercourse, cereal intake, dried fruit intake, and average total household income before tax have emerged as newly identified risk factors for PD. Conversely, maternal smoking around birth, playing computer games, salt added to food, and time spent watching television have been identified as novel protective factors against PD. The integration of phenotypic and genomic data may help to identify risk factors and prevention targets for PD.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"7 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkinson’s disease is associated with clonal hematopoiesis with TET2 mutation","authors":"Kyung Ah Woo, Han-Joon Kim, Chan Young Lee, Jung Hwan Shin, Choonghyun Sun, Hogune Im, Hongyul An, Jiwoo Lim, Su-Yeon Choi, Youngil Koh, Beomseok Jeon","doi":"10.1038/s41531-024-00784-1","DOIUrl":"https://doi.org/10.1038/s41531-024-00784-1","url":null,"abstract":"<p>Clonal hematopoiesis of indeterminate potential (CHIP), a premalignant expansion of mutated hematopoietic stem cells, is linked to immune alterations. Given the role of neuroinflammation and immune dysfunction in Parkinson’s disease (PD), we hypothesized a connection between CHIP and PD. We analyzed peripheral blood DNA from 341 PD, 92 isolated REM sleep behavior disorder (iRBD) patients, and 5003 controls using targeted sequencing of 24 genes associated with hematologic neoplasms. PD cases were classified by clinical progression mode: fast, slow, and typical. Using multivariable logistic regression models, CHIP prevalence was assessed against controls with a 1.0% variant allele fraction threshold. CHIP with <i>TET2</i> mutations was more prevalent in PD than controls (aOR 1.75, 95% CI 1.11–2.77, <i>p</i> = 0.017), particularly in the fast motor progression subgroup (aOR 3.19, <i>p</i> = 0.004). No distinct associations were observed with iRBD. PD is linked to increased odds of CHIP with <i>TET2</i> mutations, suggesting immune dysregulation in PD pathophysiology.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"1 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural correlates of bradykinesia in Parkinson’s disease: a kinematic and functional MRI study","authors":"Elisabetta Sarasso, Andrea Gardoni, Lucia Zenere, Daniele Emedoli, Roberta Balestrino, Andrea Grassi, Silvia Basaia, Chiara Tripodi, Elisa Canu, Massimo Malcangi, Elisa Pelosin, Maria Antonietta Volontè, Davide Corbetta, Massimo Filippi, Federica Agosta","doi":"10.1038/s41531-024-00783-2","DOIUrl":"https://doi.org/10.1038/s41531-024-00783-2","url":null,"abstract":"<p>Bradykinesia is defined as a “<i>complex</i>” of motor alterations including decreased movement amplitude and/or speed and tendency to reduce them with movement repetition (sequence effect). This study aimed at investigating the neural and kinematic correlates of bradykinesia during hand-tapping in people with Parkinson’s disease (pwPD) relative to healthy controls. Twenty-five pwPD and 25 age- and sex-matched healthy controls underwent brain functional MRI (fMRI) during a hand-tapping task: subjects alternatively opened and closed their right hand as fully and quickly as possible. Hand-tapping kinematic parameters were objectively measured during the fMRI task using an optical fibre glove. During the fMRI task, pwPD showed reduced hand-tapping amplitude (hypokinesia) and a greater sequence effect. PwPD relative to healthy controls showed a reduced activity of fronto-parietal areas, middle cingulum/supplementary motor area (SMA), parahippocampus, pallidum/thalamus and motor cerebellar areas. Moreover, pwPD showed an increased activity of brain cognitive areas such as superior temporal gyrus, posterior cingulum, and cerebellum crus I. The decreased activity of cerebellum IV–V–VI, vermis IV–V, inferior frontal gyrus, and cingulum/SMA correlated with hypokinesia and with the sequence effect. Interestingly, a reduced activity of areas involved in motor planning and timing correlated both with hypokinesia and with the sequence effect in pwPD. This study has the major strength of collecting objective motor parameters and brain activity simultaneously, providing a unique opportunity to investigate the neural correlates of the “bradykinesia complex”.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"31 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calbindin and Girk2/Aldh1a1 define resilient vs vulnerable dopaminergic neurons in a primate Parkinson’s disease model","authors":"Natalia López-González del Rey, Nagore Hernández-Pinedo, Megan Carrillo, María del Cerro, Noelia Esteban-García, Inés Trigo-Damas, Mariana H. G. Monje, José L. Lanciego, Carmen Cavada, José A. Obeso, Javier Blesa","doi":"10.1038/s41531-024-00777-0","DOIUrl":"https://doi.org/10.1038/s41531-024-00777-0","url":null,"abstract":"<p>The differential vulnerability of dopaminergic neurons of the <i>substantia nigra pars compacta</i> (SNc) is a critical and unresolved question in Parkinson´s disease. Studies in mice show diverse susceptibility of subpopulations of nigral dopaminergic neurons to various toxic agents. In the primate midbrain, the molecular phenotypes of dopaminergic neurons and their differential vulnerability are poorly characterized. We performed a detailed histological study to determine the anatomical distribution of different molecular phenotypes within identified midbrain neurons and their selective vulnerability in control and MPTP-treated monkeys. In the ventral tier of the SNc (<i>nigrosome</i>), neurons rich in Aldh1a1 and Girk2 are intermingled, whereas calbindin is the marker that best identifies the most resilient neurons located in the dorsal tier and ventral tegmental area, recapitulating the well-defined dorsoventral axis of susceptibility to degeneration of dopaminergic neurons. In particular, a loss of Aldh1a1+ neurons in the ventral SNc was observed in parallel to the progressive development of parkinsonism. Aldh1a1+ neurons were the main population of vulnerable dopaminergic nigrostriatal-projecting neurons, while Aldh1a1- neurons giving rise to nigropallidal projections remained relatively preserved. Moreover, bundles of entwined Aldh1a1+ dendrites with long trajectories extending towards the <i>substantia nigra pars reticulata</i> emerged from clusters of Aldh1a1+ neurons and colocalized with dense cannabinoid receptor 1 afferent fibers likely representing part of the striatonigral projection that is affected in human disorders, including Parkinson´s disease. In conclusion, vulnerable nigrostriatal-projecting neurons can be identified by using Aldh1a1 and Girk2. Further studies are needed to define the afferent/efferent projection patterns of these most vulnerable neurons.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"15 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring causal effects of sarcopenia on risk and progression of Parkinson disease by Mendelian randomization","authors":"Tao Wang, Jiaquan Geng, Xi Zeng, Ruijiang Han, Young Eun Huh, Jiajie Peng","doi":"10.1038/s41531-024-00782-3","DOIUrl":"https://doi.org/10.1038/s41531-024-00782-3","url":null,"abstract":"<p>Previous observational studies suggested that sarcopenia is associated with Parkinson disease (PD), but it is unclear whether this association is causal. The objective of this study was to examine causal associations between sarcopenia-related traits and the risk or progression of PD using a Mendelian randomization (MR) approach. Two-sample bidirectional MR analyses were conducted to evaluate causal relationships. Genome-wide association study (GWAS) summary statistics for sarcopenia-related traits, including right handgrip strength (<i>n</i> = 461,089), left handgrip strength (<i>n</i> = 461,026), and appendicular lean mass (<i>n</i> = 450,243), were retrieved from the IEU OpenGWAS database. GWAS data for the risk of PD were derived from the FinnGen database (4235 cases; 373,042 controls). Summary-level data for progression of PD, including progression to Hoehn and Yahr stage 3, progression to dementia, and development of levodopa-induced dyskinesia, were obtained from a recent GWAS publication on progression of PD in 4093 patients from 12 longitudinal cohorts. Significant causal associations identified in MR analysis were verified through a polygenic score (PGS)-based approach and pathway enrichment analysis using genotype data from the Parkinson’s Progression Markers Initiative. MR results supported a significant causal influence of right handgrip strength (odds ratio [OR] = 0.152, 95% confidence interval [CI] = 0.055–0.423, adjusted <i>P</i> = 0.0036) and appendicular lean mass (OR = 0.597, 95% CI = 0.440–0.810, adjusted <i>P</i> = 0.0111) on development of levodopa-induced dyskinesia. In Cox proportional hazard analysis, higher PGSs for right handgrip strength (hazard ratio [HR] = 0.225, 95% CI = 0.095–0.530, adjusted <i>P</i> = 0.0019) and left handgrip strength (HR = 0.303, 95% CI = 0.121–0.59, adjusted <i>P</i> = 0.0323) were significantly associated with a lower risk of developing levodopa-induced dyskinesia, after adjusting for covariates. Pathway enrichment analysis revealed that genome-wide significant single-nucleotide polymorphisms for right handgrip strength were substantially enriched in biological pathways involved in the control of synaptic plasticity. This study provides genetic evidence of the protective role of handgrip strength or appendicular lean mass on the development of levodopa-induced dyskinesia in PD. Sarcopenia-related traits can be promising prognostic markers for levodopa-induced dyskinesia and potential therapeutic targets for preventing levodopa-induced dyskinesia in patients with PD.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"6 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing age and the rs6265 BDNF SNP are permissive to graft-induced dyskinesias in parkinsonian rats","authors":"Natosha M. Mercado, Carlye Szarowicz, Jennifer A. Stancati, Caryl E. Sortwell, Samuel A. Boezwinkle, Timothy J. Collier, Margaret E. Caulfield, Kathy Steece-Collier","doi":"10.1038/s41531-024-00771-6","DOIUrl":"https://doi.org/10.1038/s41531-024-00771-6","url":null,"abstract":"<p>The rs6265 single nucleotide polymorphism (SNP) in the gene for brain-derived neurotrophic factor is a common variant that alters therapeutic outcomes for individuals with Parkinson’s disease (PD). We previously investigated the effects of this SNP on the experimental therapeutic approach of neural grafting, demonstrating that young adult parkinsonian rats carrying the variant Met allele exhibited enhanced graft function compared to wild-type rats and also exclusively developed aberrant graft-induced dyskinesias (GID). Aging is the primary risk factor for PD and reduces graft efficacy. Here we investigated whether aging interacts with this SNP to further alter cell transplantation outcomes. We hypothesized that aging would reduce enhancement of graft function associated with this genetic variant and exacerbate GID in all grafted subjects. Unexpectedly, beneficial graft function was maintained in aged rs6265 subjects. However, aging was permissive to GID induction, regardless of genotype, with the greatest incidence and severity found in rs6265-expressing animals.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"20 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142045643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotection of low dose carbon monoxide in Parkinson’s disease models commensurate with the reduced risk of Parkinson’s among smokers","authors":"K. N. Rose, M. Zorlu, A. Fassini, H. Lee, W. Cai, X. Xue, S. Lin, P. Kivisakk, M. A. Schwarzschild, X. Chen, S. N. Gomperts","doi":"10.1038/s41531-024-00763-6","DOIUrl":"https://doi.org/10.1038/s41531-024-00763-6","url":null,"abstract":"<p>Paradoxically, cigarette smoking is associated with a reduced risk of Parkinson’s Disease (PD). This led us to hypothesize that carbon monoxide (CO) levels, which are constitutively but modestly elevated in smokers, might contribute to neuroprotection. Using rodent models of PD based on α-synuclein (αSyn) accumulation and oxidative stress, we show that low-dose CO mitigates neurodegeneration and reduces αSyn pathology. Oral CO administration activated signaling cascades mediated by heme oxygenase-1 (HO-1), which have been implicated in limiting oxidative stress, and in promoting αSyn degradation, thereby conferring neuroprotection. Consistent with the neuroprotective effect of smoking, HO-1 levels in cerebrospinal fluid were higher in human smokers compared to nonsmokers. Moreover, in PD brain samples, HO-1 levels were higher in neurons without αSyn pathology. Thus, CO in rodent PD models reduces pathology and increases oxidative stress responses, phenocopying possible protective effects of smoking evident in PD patients. These data highlight the potential for low-dose CO-modulated pathways to slow symptom onset and limit pathology in PD patients.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"20 1","pages":""},"PeriodicalIF":8.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142021960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum neurofilament light at diagnosis: a prognostic indicator for accelerated disease progression in Parkinson's Disease.","authors":"Camilla Christina Pedersen, Anastasia Ushakova, Guido Alves, Ole-Bjørn Tysnes, Kaj Blennow, Henrik Zetterberg, Jodi Maple-Grødem, Johannes Lange","doi":"10.1038/s41531-024-00768-1","DOIUrl":"10.1038/s41531-024-00768-1","url":null,"abstract":"<p><p>Neurofilament light chain (NFL) is elevated in neurodegenerative diseases, including Parkinson's disease (PD). This study aimed to investigate serum NFL in newly diagnosed PD and its association with cognitive and motor decline over 10 years. Serum NFL levels were measured in PD patients and controls from the ParkWest study at diagnosis (baseline) and after 3 and 5 years. Mixed-effects regression analyzed changes in NFL and the association with annual changes in MMSE and UPDRS-III scores over 10 years. PD patients had elevated serum NFL at all visits and a faster annual increase over 5 years compared to controls (0.09 pg/mL per year; p = 0.029). Higher baseline NFL predicted faster cognitive decline β -0.77 transformed MMSE; p = 0.010), and a 40% NFL increase predicted future motor decline (β 0.28 UPDRS-III; p = 0.004). Elevated serum NFL in early PD is linked to faster cognitive and motor impairment, suggesting its prognostic value in PD biomarker panels.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":"162"},"PeriodicalIF":6.7,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the clinical utility of inertial sensors for home monitoring in Parkinson's disease: a comprehensive review.","authors":"Stefano Sapienza, Olena Tsurkalenko, Marijus Giraitis, Alan Castro Mejia, Gelani Zelimkhanov, Isabel Schwaninger, Jochen Klucken","doi":"10.1038/s41531-024-00755-6","DOIUrl":"10.1038/s41531-024-00755-6","url":null,"abstract":"<p><p>This review screened 296 articles on wearable sensors for home monitoring of people with Parkinson's Disease within the PubMed Database, from January 2017 to May 2023. A three-level maturity framework was applied for classifying the aims of 59 studies included: demonstrating technical efficacy, diagnostic sensitivity, or clinical utility. As secondary analysis, user experience (usability and patient adherence) was evaluated. The evidences provided by the studies were categorized and stratified according to the level of maturity. Our results indicate that approximately 75% of articles investigated diagnostic sensitivity, i.e. correlation of sensor-data with clinical parameters. Evidence of clinical utility, defined as improvement on health outcomes or clinical decisions after the use of the wearables, was found only in nine papers. A third of the articles included reported evidence of user experience. Future research should focus more on clinical utility, to facilitate the translation of research results within the management of Parkinson's Disease.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":"10 1","pages":"161"},"PeriodicalIF":6.7,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}