NPJ Parkinson's Disease最新文献

{"title":"Genetic and phenotypic characterization of Parkinson’s disease at the clinic-wide level","authors":"Thomas F. Tropea, Whitney Hartstone, Noor Amari, Dylan Baum, Jacqueline Rick, Eunran Suh, Hanwen Zhang, Rachel A. Paul, Noah Han, Rebecca Zack, Eliza M. Brody, Isabela Albuja, Justin James, Meredith Spindler, Andres Deik, Whitley W. Aamodt, Nabila Dahodwala, Ali Hamedani, Aaron Lasker, Howard Hurtig, Matthew Stern, Daniel Weintraub, Pavan Vaswani, Allison W. Willis, Andrew Siderowf, Sharon X. Xie, Vivianna Van Deerlin, Alice S. Chen-Plotkin","doi":"10.1038/s41531-024-00690-6","DOIUrl":"https://doi.org/10.1038/s41531-024-00690-6","url":null,"abstract":"<p>Observational studies in Parkinson’s disease (PD) deeply characterize relatively small numbers of participants. The Molecular Integration in Neurological Diagnosis Initiative seeks to characterize molecular and clinical features of every PD patient at the University of Pennsylvania (UPenn). The objectives of this study are to determine the feasibility of genetic characterization in PD and assess clinical features by sex and <i>GBA1/LRRK2</i> status on a clinic-wide scale. All PD patients with clinical visits at the UPenn PD Center between 9/2018 and 12/2022 were eligible. Blood or saliva were collected, and a clinical questionnaire administered. Genotyping at 14 <i>GBA1</i> and 8 <i>LRRK2</i> variants was performed. PD symptoms were compared by sex and gene groups. 2063 patients were approached and 1,689 (82%) were enrolled, with 374 (18%) declining to participate. 608 (36%) females were enrolled, 159 (9%) carried a <i>GBA1</i> variant, and 44 (3%) carried a <i>LRRK2</i> variant. Compared with males, females across gene groups more frequently reported dystonia (53% vs 46%, <i>p</i> = 0.01) and anxiety (64% vs 55%, <i>p</i> &lt; 0.01), but less frequently reported cognitive impairment (10% vs 49%, <i>p</i> &lt; 0.01) and vivid dreaming (53% vs 60%, <i>p</i> = 0.01). <i>GBA1</i> variant carriers more frequently reported anxiety (67% vs 57%, <i>p</i> = 0.04) and depression (62% vs 46%, <i>p</i> &lt; 0.01) than non-carriers; <i>LRRK2</i> variant carriers did not differ from non-carriers. We report feasibility for near-clinic-wide enrollment and characterization of individuals with PD during clinical visits at a high-volume academic center. Clinical symptoms differ by sex and <i>GBA1</i>, but not <i>LRRK2</i>, status.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821690","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":"Structural underpinnings and long-term effects of resilience in Parkinson’s disease","authors":"Verena Dzialas, Merle C. Hoenig, Stéphane Prange, Gérard N. Bischof, Alexander Drzezga, Thilo van Eimeren","doi":"10.1038/s41531-024-00699-x","DOIUrl":"https://doi.org/10.1038/s41531-024-00699-x","url":null,"abstract":"<p>Resilience in neuroscience generally refers to an individual’s capacity to counteract the adverse effects of a neuropathological condition. While resilience mechanisms in Alzheimer’s disease are well-investigated, knowledge regarding its quantification, neurobiological underpinnings, network adaptations, and long-term effects in Parkinson’s disease is limited. Our study involved 151 Parkinson’s patients from the Parkinson’s Progression Marker Initiative Database with available Magnetic Resonance Imaging, Dopamine Transporter Single-Photon Emission Computed Tomography scans, and clinical information. We used an improved prediction model linking neuropathology to symptom severity to estimate individual resilience levels. Higher resilience levels were associated with a more active lifestyle, increased grey matter volume in motor-associated regions, a distinct structural connectivity network and maintenance of relative motor functioning for up to a decade. Overall, the results indicate that relative maintenance of motor function in Parkinson’s patients may be associated with greater neuronal substrate, allowing higher tolerance against neurodegenerative processes through dynamic network restructuring.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821211","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":"Progression subtypes in Parkinson’s disease identified by a data-driven multi cohort analysis","authors":"Tom Hähnel, Tamara Raschka, Stefano Sapienza, Jochen Klucken, Enrico Glaab, Jean-Christophe Corvol, Björn H. Falkenburger, Holger Fröhlich","doi":"10.1038/s41531-024-00712-3","DOIUrl":"https://doi.org/10.1038/s41531-024-00712-3","url":null,"abstract":"<p>The progression of Parkinson’s disease (PD) is heterogeneous across patients, affecting counseling and inflating the number of patients needed to test potential neuroprotective treatments. Moreover, disease subtypes might require different therapies. This work uses a data-driven approach to investigate how observed heterogeneity in PD can be explained by the existence of distinct PD progression subtypes. To derive stable PD progression subtypes in an unbiased manner, we analyzed multimodal longitudinal data from three large PD cohorts and performed extensive cross-cohort validation. A latent time joint mixed-effects model (LTJMM) was used to align patients on a common disease timescale. Progression subtypes were identified by variational deep embedding with recurrence (VaDER). In each cohort, we identified a fast-progressing and a slow-progressing subtype, reflected by different patterns of motor and non-motor symptoms progression, survival rates, treatment response, features extracted from DaTSCAN imaging and digital gait assessments, education, and Alzheimer’s disease pathology. Progression subtypes could be predicted with ROC-AUC up to 0.79 for individual patients when a one-year observation period was used for model training. Simulations demonstrated that enriching clinical trials with fast-progressing patients based on these predictions can reduce the required cohort size by 43%. Our results show that heterogeneity in PD can be explained by two distinct subtypes of PD progression that are stable across cohorts. These subtypes align with the brain-first vs. body-first concept, which potentially provides a biological explanation for subtype differences. Our predictive models will enable clinical trials with significantly lower sample sizes by enriching fast-progressing patients.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821280","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":"PARKIN is not required to sustain OXPHOS function in adult mammalian tissues","authors":"Roberta Filograna, Jule Gerlach, Hae-Na Choi, Giovanni Rigoni, Michela Barbaro, Mikael Oscarson, Seungmin Lee, Katarina Tiklova, Markus Ringnér, Camilla Koolmeister, Rolf Wibom, Sara Riggare, Inger Nennesmo, Thomas Perlmann, Anna Wredenberg, Anna Wedell, Elisa Motori, Per Svenningsson, Nils-Göran Larsson","doi":"10.1038/s41531-024-00707-0","DOIUrl":"https://doi.org/10.1038/s41531-024-00707-0","url":null,"abstract":"<p>Loss-of-function variants in the <i>PRKN</i> gene encoding the ubiquitin E3 ligase PARKIN cause autosomal recessive early-onset Parkinson’s disease (PD). Extensive in vitro and in vivo studies have reported that PARKIN is involved in multiple pathways of mitochondrial quality control, including mitochondrial degradation and biogenesis. However, these findings are surrounded by substantial controversy due to conflicting experimental data. In addition, the existing PARKIN-deficient mouse models have failed to faithfully recapitulate PD phenotypes. Therefore, we have investigated the mitochondrial role of PARKIN during ageing and in response to stress by employing a series of conditional Parkin knockout mice. We report that PARKIN loss does not affect oxidative phosphorylation (OXPHOS) capacity and mitochondrial DNA (mtDNA) levels in the brain, heart, and skeletal muscle of aged mice. We also demonstrate that PARKIN deficiency does not exacerbate the brain defects and the pro-inflammatory phenotype observed in mice carrying high levels of mtDNA mutations. To rule out compensatory mechanisms activated during embryonic development of <i>Parkin</i>-deficient mice, we generated a mouse model where loss of PARKIN was induced in adult dopaminergic (DA) neurons. Surprisingly, also these mice did not show motor impairment or neurodegeneration, and no major transcriptional changes were found in isolated midbrain DA neurons. Finally, we report a patient with compound heterozygous <i>PRKN</i> pathogenic variants that lacks PARKIN and has developed PD. The PARKIN deficiency did not impair OXPHOS activities or induce mitochondrial pathology in skeletal muscle from the patient. Altogether, our results argue that PARKIN is dispensable for OXPHOS function in adult mammalian tissues.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814584","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":"Author Correction: Machine Learning in the Parkinson's disease smartwatch (PADS) dataset.","authors":"Julian Varghese, Alexander Brenner, Michael Fujarski, Catharina Marie van Alen, Lucas Plagwitz, Tobias Warnecke","doi":"10.1038/s41531-024-00710-5","DOIUrl":"https://doi.org/10.1038/s41531-024-00710-5","url":null,"abstract":"","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11056371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868332","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":"No evidence for an association of voxel-based morphometry with short-term non-motor outcomes in deep brain stimulation for Parkinson’s disease","authors":"Philipp Alexander Loehrer, Wibke Schumacher, Stefanie T. Jost, Monty Silverdale, Jan Niklas Petry-Schmelzer, Anna Sauerbier, Alexandra Gronostay, Veerle Visser-Vandewalle, Gereon R. Fink, Julian Evans, Max Krause, Alexandra Rizos, Angelo Antonini, Keyoumars Ashkan, Pablo Martinez-Martin, Christian Gaser, K. Ray Chaudhuri, Lars Timmermann, Juan Carlos Baldermann, Haidar S. Dafsari","doi":"10.1038/s41531-024-00695-1","DOIUrl":"https://doi.org/10.1038/s41531-024-00695-1","url":null,"abstract":"<p>Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established therapy in advanced Parkinson’s disease (PD). Motor and non-motor outcomes, however, show considerable inter-individual variability. Preoperative morphometry-based metrics have recently received increasing attention to explain treatment effects. As evidence for the prediction of non-motor outcomes is limited, we sought to investigate the association between metrics of voxel-based morphometry and short-term non-motor outcomes following STN-DBS in this prospective open-label study. Forty-nine PD patients underwent structural MRI and a comprehensive clinical assessment at preoperative baseline and 6-month follow-up. Voxel-based morphometry was used to assess associations between cerebral volume and non-motor outcomes corrected for multiple comparisons using a permutation-based approach. We replicated existing results associating volume loss of the superior frontal cortex with subpar motor outcomes. Overall non-motor burden, however, was not significantly associated with morphometric features, limiting its use as a marker to inform patient selection and holistic preoperative counselling.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648610","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":"Lysosomal genes contribute to Parkinson’s disease near agriculture with high intensity pesticide use","authors":"Kathie J. Ngo, Kimberly C. Paul, Darice Wong, Cynthia D. J. Kusters, Jeff M. Bronstein, Beate Ritz, Brent L. Fogel","doi":"10.1038/s41531-024-00703-4","DOIUrl":"https://doi.org/10.1038/s41531-024-00703-4","url":null,"abstract":"<p>Parkinson’s disease (PD), the second most common neurodegenerative disorder, develops sporadically, likely through a combination of polygenic and environmental factors. Previous studies associate pesticide exposure and genes involved in lysosomal function with PD risk. We evaluated the frequency of variants in lysosomal function genes among patients from the Parkinson’s, Environment, and Genes (PEG) study with ambient pesticide exposure from agricultural sources. 757 PD patients, primarily of White European/non-Hispanic ancestry (75%), were screened for variants in 85 genes using a custom amplicon panel. Variant enrichment was calculated against the Genome Aggregation Database (gnomAD). Enriched exonic variants were prioritized by exposure to a cluster of pesticides used on cotton and severity of disease progression in a subset of 386 patients subdivided by race/ethnicity. Gene enrichment analysis identified 36 variants in 26 genes in PEG PD patients. Twelve of the identified genes (12/26, 46%) had multiple enriched variants and/or a single enriched variant present in multiple individuals, representing 61% (22/36) of the observed variation in the cohort. The majority of enriched variants (26/36, 72%) were found in genes contributing to lysosomal function, particularly autophagy, and were bioinformatically deemed functionally deleterious (31/36, 86%). We conclude that, in this study, variants in genes associated with lysosomal function, notably autophagy, were enriched in PD patients exposed to agricultural pesticides suggesting that altered lysosomal function may generate an underlying susceptibility for developing PD with pesticide exposure. Further study of gene-environment interactions targeting lysosomal function may improve understanding of PD risk in individuals exposed to pesticides.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140642286","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":"Ultrastructural localization of Porphyromonas gingivalis gingipains in the substantia nigra of Parkinson’s disease brains","authors":"Florian Ermini, Victoria F. Low, Jennifer J. Song, Adelie Y. S. Tan, Richard L. M. Faull, Michael Dragunow, Maurice A. Curtis, Stephen S. Dominy","doi":"10.1038/s41531-024-00705-2","DOIUrl":"https://doi.org/10.1038/s41531-024-00705-2","url":null,"abstract":"<p>Gingipains are protease virulence factors produced by <i>Porphyromonas gingivalis</i>, a Gram-negative bacterium best known for its role in chronic periodontitis. Gingipains were recently identified in the middle temporal gyrus of postmortem Alzheimer’s disease (AD) brains, where gingipain load correlated with AD diagnosis and tau and ubiquitin pathology. Since AD and Parkinson’s disease (PD) share some overlapping pathologic features, including nigral pathology and Lewy bodies, the current study explored whether gingipains are present in the substantia nigra pars compacta of PD brains. In immunohistochemical techniques and multi-channel fluorescence studies, gingipain antigens were abundant in dopaminergic neurons in the substantia nigra of both PD and neurologically normal control brains. 3-dimensional reconstructions of Lewy body containing neurons revealed that gingipains associated with the periphery of alpha-synuclein aggregates but were occasionally observed inside aggregates. In vitro proteomic analysis demonstrated that recombinant alpha-synuclein is cleaved by lysine-gingipain, generating multiple alpha-synuclein fragments including the non-amyloid component fragments. Immunogold electron microscopy with co-labeling of gingipains and alpha-synuclein confirmed the occasional colocalization of gingipains with phosphorylated (pSER129) alpha-synuclein. In dopaminergic neurons, gingipains localized to the perinuclear cytoplasm, neuromelanin, mitochondria, and nucleus. These data suggest that gingipains localize in dopaminergic neurons in the substantia nigra and interact with alpha-synuclein.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140642244","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":"Longitudinal cognitive decline characterizes the profile of non-PD-manifest GBA1 mutation carriers","authors":"Benjamin Roeben, Inga Liepelt-Scarfone, Stefanie Lerche, Milan Zimmermann, Isabel Wurster, Ulrike Sünkel, Claudia Schulte, Christian Deuschle, Gerhard W. Eschweiler, Walter Maetzler, Thomas Gasser, Daniela Berg, Kathrin Brockmann","doi":"10.1038/s41531-024-00706-1","DOIUrl":"https://doi.org/10.1038/s41531-024-00706-1","url":null,"abstract":"<p>With disease-modifying treatment for Parkinson’s disease (PD) associated with variants in the glucocerebrosidase gene (<i>GBA1</i>) under way, the challenge to design clinical trials with non-PD-manifest <i>GBA</i> mutation carriers (GBA1_NMC) comes within close reach. To delineate trajectories of motor and non-motor markers as well as serum neurofilament light (sNfL) levels and to evaluate clinical endpoints as outcomes for clinical trials in GBA1_NMC, longitudinal data of 56 GBA1_NMC carriers and 112 age- and sex-matched <i>GBA1</i> wildtype participants (GBA1_wildtype) with up to 9 years of follow-up was analyzed using linear mixed-effects models (LMEM) and Kaplan–Meier survival analysis of clinical endpoints for motor and cognitive function. GBA1_NMC showed worse performance in Pegboard, 20 m fast walking, global cognition as well as in executive and memory function at baseline. Longitudinally, LMEM revealed a higher annual increase of the MDS-UPDRS III bradykinesia subscore in GBA1_NMC compared to GBA1_wildtype, but comparable trajectories of all other motor and non-motor markers as well as sNfL. Kaplan–Meier survival analysis showed a significantly earlier progression to clinical endpoints of cognitive decline in GBA1_NMC. Incidence of PD was significantly higher in GBA1_NMC. In conclusion, our study extends data on GBA1_NMC indicating early cognitive decline as a potentially characteristic feature. Comprehensive longitudinal assessments of cognitive function are crucial to delineate the evolution of early changes in GBA1_NMC enabling a more accurate stratification and allow for a more precise definition of trial design and sample size.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632314","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":"Diet and the gut microbiome in patients with Parkinson’s disease","authors":"Dayoon Kwon, Keren Zhang, Kimberly C. Paul, Aline D. Folle, Irish Del Rosario, Jonathan P. Jacobs, Adrienne M. Keener, Jeff M. Bronstein, Beate Ritz","doi":"10.1038/s41531-024-00681-7","DOIUrl":"https://doi.org/10.1038/s41531-024-00681-7","url":null,"abstract":"<p>It has been suggested that gut microbiota influence Parkinson’s disease (PD) via the gut–brain axis. Here, we examine associations between diet and gut microbiome composition and its predicted functional pathways in patients with PD. We assessed gut microbiota in fecal samples from 85 PD patients in central California using 16S rRNA gene sequencing. Diet quality was assessed by calculating the Healthy Eating Index 2015 (HEI-2015) based on the Diet History Questionnaire II. We examined associations of diet quality, fiber, and added sugar intake with microbial diversity, composition, taxon abundance, and predicted metagenomic profiles, adjusting for age, sex, race/ethnicity, and sequencing platform. Higher HEI scores and fiber intake were associated with an increase in putative anti-inflammatory butyrate-producing bacteria, such as the genera <i>Butyricicoccus</i> and <i>Coprococcus 1</i>. Conversely, higher added sugar intake was associated with an increase in putative pro-inflammatory bacteria, such as the genera <i>Klebsiella</i>. Predictive metagenomics suggested that bacterial genes involved in the biosynthesis of lipopolysaccharide decreased with higher HEI scores, whereas a simultaneous decrease in genes involved in taurine degradation indicates less neuroinflammation. We found that a healthy diet, fiber, and added sugar intake affect the gut microbiome composition and its predicted metagenomic function in PD patients. This suggests that a healthy diet may support gut microbiome that has a positive influence on PD risk and progression.</p>","PeriodicalId":19706,"journal":{"name":"NPJ Parkinson's Disease","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632297","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}