Objective: The aim of this study was to identify the genetic cause of two cases of Kufs disease in the same family. The two affected individuals exhibited different levels of severity under magnetic resonance imaging (MRI). Methods: Whole-exome sequencing was performed on affected individuals, and the candidate gene was confirmed by Sanger sequencing. Western blot analysis was used to evaluate the level of expression of CLN6 protein in 239T cells. Results: We identified a novel homozygous mutation of the CLN6 gene (c.14G>T, p.Arg5Leu) in a consanguineous Chinese family in which two people had Kufs disease. Both patients exhibited seizures and progressive psychomotor decline and mental deterioration without visual impairment. They had different ages of onset, although they carried the same missense mutation. The affected female showed a pronounced abnormal MRI signal in the bilateral hippocampus, while her younger brother only showed a very slight abnormal signal. Further study showed that this missense mutation could decrease the level of expression of CLN6 protein. Conclusions: A novel homozygous mutation of the CLN6 gene was identified, and patients with the same mutation showed different ages of onset and different levels of severity under MRI. Significance: Our study established that the same CLN6 mutation could produce different phenotypes in patients, and it has expanded the mutational and phenotypical spectrum of the CLN6 gene.
{"title":"Juvenile-Onset Kufs Disease in a Chinese Consanguineous Family due to CLN6 Mutation","authors":"Weimin Jia, Yalin Luo, Jiuxiang Wang, Yue Yang, Wenming Yang, Xianqin Zhang","doi":"10.1159/000524784","DOIUrl":"https://doi.org/10.1159/000524784","url":null,"abstract":"Objective: The aim of this study was to identify the genetic cause of two cases of Kufs disease in the same family. The two affected individuals exhibited different levels of severity under magnetic resonance imaging (MRI). Methods: Whole-exome sequencing was performed on affected individuals, and the candidate gene was confirmed by Sanger sequencing. Western blot analysis was used to evaluate the level of expression of CLN6 protein in 239T cells. Results: We identified a novel homozygous mutation of the CLN6 gene (c.14G>T, p.Arg5Leu) in a consanguineous Chinese family in which two people had Kufs disease. Both patients exhibited seizures and progressive psychomotor decline and mental deterioration without visual impairment. They had different ages of onset, although they carried the same missense mutation. The affected female showed a pronounced abnormal MRI signal in the bilateral hippocampus, while her younger brother only showed a very slight abnormal signal. Further study showed that this missense mutation could decrease the level of expression of CLN6 protein. Conclusions: A novel homozygous mutation of the CLN6 gene was identified, and patients with the same mutation showed different ages of onset and different levels of severity under MRI. Significance: Our study established that the same CLN6 mutation could produce different phenotypes in patients, and it has expanded the mutational and phenotypical spectrum of the CLN6 gene.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48590932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Aiello, Margherita Grosso, Claudia Caracciolo, Adele Andriulo, S. Buscone, Monica Ottobrini, C. Luzzatti
Background: In Parkinson’s disease (PD), verb-naming tasks (VNTs) have been proposed as superior to noun-naming ones in detecting language deficits, although such a hypothesis is not supported at a statistical level. Objectives: The main aim of this study was to provide diagnostic accuracy evidence for a VNT and noun-naming task (NNT) in detecting cognitive impairment (CI) in PD patients. Method: Thirty-three consecutive PD patients were subdivided into participants with (PD-CI; N = 12) or without CI (cognitively unimpaired, PD-CU; N = 21), based on a raw score ≤25 or >25 on the Mini-Mental State Examination, respectively. The NNT and VNT by Neuropsychologia [2006 Jan;44(1):73–89] were administered. Diagnostic accuracy of the NNT and VNT was assessed through receiver-operating characteristics analyses by comparing PD-CU to PD-CI patients. At the optimal cut-off, sensitivity, specificity, positive and negative predictive values (PPV, NPV), and likelihood ratios (LR+, LR−) were separately tested for the NNT and VNT against PD-CU versus PD-CI classification. Results: Diagnostic accuracy was higher for the NNT (AUC = 0.85; p = 0.001) versus the VNT (AUC = 0.68; p = 0.092). Consistently, the NNT yielded higher sensitivity, specificity, and post-test features than the VNT (NNT: sensitivity = 0.75, specificity = 0.81, PPV = 0.69, NPV = 0.85, LR+ = 3.94, LR− = 0.31; VNT: sensitivity = 0.67, specificity = 0.67, PPV = 0.53, NPV = 0.78, LR+ = 2, LR− = 0.5). Conclusions: In accordance with the Movement Disorders Society guidelines, NNTs are diagnostically sound psychometric instruments to discriminate PD patients with versus without CI. However, these findings need replication by (1) employing a gold standard different from the Mini-Mental State Examination, which does not capture the full range of CI in this population and (2) subdividing PD patients into those with mild CI and dementia.
{"title":"Diagnostic Accuracy of Noun- and Verb-Naming Tasks in Detecting Cognitive Impairment in Parkinson’s Disease","authors":"E. Aiello, Margherita Grosso, Claudia Caracciolo, Adele Andriulo, S. Buscone, Monica Ottobrini, C. Luzzatti","doi":"10.1159/000525195","DOIUrl":"https://doi.org/10.1159/000525195","url":null,"abstract":"Background: In Parkinson’s disease (PD), verb-naming tasks (VNTs) have been proposed as superior to noun-naming ones in detecting language deficits, although such a hypothesis is not supported at a statistical level. Objectives: The main aim of this study was to provide diagnostic accuracy evidence for a VNT and noun-naming task (NNT) in detecting cognitive impairment (CI) in PD patients. Method: Thirty-three consecutive PD patients were subdivided into participants with (PD-CI; N = 12) or without CI (cognitively unimpaired, PD-CU; N = 21), based on a raw score ≤25 or >25 on the Mini-Mental State Examination, respectively. The NNT and VNT by Neuropsychologia [2006 Jan;44(1):73–89] were administered. Diagnostic accuracy of the NNT and VNT was assessed through receiver-operating characteristics analyses by comparing PD-CU to PD-CI patients. At the optimal cut-off, sensitivity, specificity, positive and negative predictive values (PPV, NPV), and likelihood ratios (LR+, LR−) were separately tested for the NNT and VNT against PD-CU versus PD-CI classification. Results: Diagnostic accuracy was higher for the NNT (AUC = 0.85; p = 0.001) versus the VNT (AUC = 0.68; p = 0.092). Consistently, the NNT yielded higher sensitivity, specificity, and post-test features than the VNT (NNT: sensitivity = 0.75, specificity = 0.81, PPV = 0.69, NPV = 0.85, LR+ = 3.94, LR− = 0.31; VNT: sensitivity = 0.67, specificity = 0.67, PPV = 0.53, NPV = 0.78, LR+ = 2, LR− = 0.5). Conclusions: In accordance with the Movement Disorders Society guidelines, NNTs are diagnostically sound psychometric instruments to discriminate PD patients with versus without CI. However, these findings need replication by (1) employing a gold standard different from the Mini-Mental State Examination, which does not capture the full range of CI in this population and (2) subdividing PD patients into those with mild CI and dementia.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46818422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: The alteration of vimentin-containing cells (VCCs) proliferation, differentiation, and migration in the brain stem of amyotrophic lateral sclerosis (ALS)-like transgenic mice (Tg(SOD1*G93A)1Gur mice) (TG mice) and wild-type mice (WT mice) at the different disease stages of TG mice was studied in this study. The aims of this study were to investigate the change features of proliferation, differentiation, and migration of endogenous neural precursor cells (NPCs) and to explore the potential effects of NPCs on restoring degenerated neurons in ALS. Methods: The proliferation, differentiation, and migration of VCCs in both different anatomic regions and neural cells of brain stem at the different stages including pre-onset (60–70 days), onset (90–100 days), and progression (120–130 days) stages of TG mice and in WT mice (control) were examined using the immunofluorescence technology. Results: VCCs were mainly distributed in the around (peripheral) central canal (CC) and the nuclei of brain stem in adult WT mice. VCCs proliferated and differentiated into astrocytes and directionally migrated from the around CC to the nuclei of brain stem, and then to the ventral part of damaged regions in brain stem at the pre-onset, onset, and progression stages of TG mice. Conclusions: The data suggest that NPCs widely distributed in the brain stem of adult TG mice can differentiate into astrocytes and migrate into damaged brain regions. This response might be a potential mechanism to repair degenerated motor neurons and restore dysfunctional neural circuitry in ALS.
{"title":"Distribution Changes of Neural Precursor Cells in the Brain Stem of Tg(SOD1*G93A)1Gur Mice","authors":"Xiaoping Shen, Chunyan Tang, Qin Kang, Yu Zhu, Shengyuan Xu, Jianxiang Jiang, Renshi Xu","doi":"10.1159/000525124","DOIUrl":"https://doi.org/10.1159/000525124","url":null,"abstract":"Objectives: The alteration of vimentin-containing cells (VCCs) proliferation, differentiation, and migration in the brain stem of amyotrophic lateral sclerosis (ALS)-like transgenic mice (Tg(SOD1*G93A)1Gur mice) (TG mice) and wild-type mice (WT mice) at the different disease stages of TG mice was studied in this study. The aims of this study were to investigate the change features of proliferation, differentiation, and migration of endogenous neural precursor cells (NPCs) and to explore the potential effects of NPCs on restoring degenerated neurons in ALS. Methods: The proliferation, differentiation, and migration of VCCs in both different anatomic regions and neural cells of brain stem at the different stages including pre-onset (60–70 days), onset (90–100 days), and progression (120–130 days) stages of TG mice and in WT mice (control) were examined using the immunofluorescence technology. Results: VCCs were mainly distributed in the around (peripheral) central canal (CC) and the nuclei of brain stem in adult WT mice. VCCs proliferated and differentiated into astrocytes and directionally migrated from the around CC to the nuclei of brain stem, and then to the ventral part of damaged regions in brain stem at the pre-onset, onset, and progression stages of TG mice. Conclusions: The data suggest that NPCs widely distributed in the brain stem of adult TG mice can differentiate into astrocytes and migrate into damaged brain regions. This response might be a potential mechanism to repair degenerated motor neurons and restore dysfunctional neural circuitry in ALS.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48965742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Front & Back Matter","authors":"P. Unschuld, R. Nitsch","doi":"10.1159/000524413","DOIUrl":"https://doi.org/10.1159/000524413","url":null,"abstract":"","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48520941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Imarisio, A. Pilotto, E. Garrafa, F. Conforti, S. Masciocchi, R. Turrone, S. Gipponi, E. Cottini, M. Rizzetti, Vanessa Porrini, C. Gussago, M. Pizzi, F. Guadagni, H. Zetterberg, N. Ashton, Abdul Hye, A. Padovani
Introduction: Previous studies reported increased plasma levels of cystatin C (Cys-C) in Parkinson’s disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodegeneration, and clinical progression in a longitudinal study. Methods: Plasma Cys-C, high-sensitive C-reactive protein, interleukin 6, and neurofilament light chain (NfL) were assessed at the baseline in 71 consecutive non-demented PD and 69 HC. PD patients underwent an extensive motor and cognitive assessment at baseline and after 2 years of follow-up. The association of Cys-C with disease severity was evaluated in a multilinear model adjusted for the effect of age, sex, disease duration, and peripheral inflammation. Results: Cys-C levels appeared to be higher in PD compared to controls and correlated with the plasma neuronal marker NfL (r = 0.204, p = 0.046). In longitudinal analyses, PD patients with higher Cys-C levels exhibited faster motor progression at 2 years of follow-up independently from the peripheral inflammatory profile. Conclusions: Cys-C was associated with higher NfL levels and a remarkably faster motor progression in PD independently from peripheral inflammation. Further studies are needed in order to understand the mechanisms underpinning the association of Cys-C with higher neuronal damage markers in neurodegenerative diseases.
{"title":"Plasma Cystatin C Correlates with Plasma NfL Levels and Predicts Disease Progression in Parkinson’s Disease","authors":"A. Imarisio, A. Pilotto, E. Garrafa, F. Conforti, S. Masciocchi, R. Turrone, S. Gipponi, E. Cottini, M. Rizzetti, Vanessa Porrini, C. Gussago, M. Pizzi, F. Guadagni, H. Zetterberg, N. Ashton, Abdul Hye, A. Padovani","doi":"10.1159/000523982","DOIUrl":"https://doi.org/10.1159/000523982","url":null,"abstract":"Introduction: Previous studies reported increased plasma levels of cystatin C (Cys-C) in Parkinson’s disease (PD) and claimed for a possible association with disease severity and progression. The aim of this study was to evaluate plasma Cys-C in PD and healthy controls (HC) and test its association with markers of peripheral inflammation, neurodegeneration, and clinical progression in a longitudinal study. Methods: Plasma Cys-C, high-sensitive C-reactive protein, interleukin 6, and neurofilament light chain (NfL) were assessed at the baseline in 71 consecutive non-demented PD and 69 HC. PD patients underwent an extensive motor and cognitive assessment at baseline and after 2 years of follow-up. The association of Cys-C with disease severity was evaluated in a multilinear model adjusted for the effect of age, sex, disease duration, and peripheral inflammation. Results: Cys-C levels appeared to be higher in PD compared to controls and correlated with the plasma neuronal marker NfL (r = 0.204, p = 0.046). In longitudinal analyses, PD patients with higher Cys-C levels exhibited faster motor progression at 2 years of follow-up independently from the peripheral inflammatory profile. Conclusions: Cys-C was associated with higher NfL levels and a remarkably faster motor progression in PD independently from peripheral inflammation. Further studies are needed in order to understand the mechanisms underpinning the association of Cys-C with higher neuronal damage markers in neurodegenerative diseases.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49131392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao Hu, T. Yamashita, Haibo Yu, Zhihong Bian, Xinran Hu, Tian Feng, Koh Tadokoro, R. Morihara, K. Abe
Background: Alzheimer’s disease (AD) is the most frequent cause of dementia among the elderly. The accumulation of amyloid beta (Aβ) and its downstream pathological events such as oxidative stress play central roles in AD. Recent studies revealed that Aβ oligomer (AβO)-induced strong neurotoxicity in SH-SY5Y cells via the induction of oxidative stress. Objective: In the present study, we investigated the effect of two antioxidants, Tocovid and Twendee-X, on AβO-induced SH-SY5Y cell damage. Methods: AβOs (2.5 μM) were applied to induce cellular damage in the SH-SY5Y cell line. Cell viability following AβO toxicity, Tau protein phosphorylation, cell morphology, and intracellular reactive oxygen species were assayed with or without different concentrations of Tocovid or Twendee-X. Results: Tocovid (60 μg/mL) and Twendee-X (150 μg/mL) significantly recovered cell viability from AβO toxicity (**p < 0.01, vs. control), attenuated Tau protein phosphorylation (**p < 0.01, vs. AβOs), improved cell morphology (**p < 0.01, vs. AβOs), and suppressed intracellular ROS (**p < 0.01, vs. AβOs) in SH-SY5Y cells. Conclusion: These findings suggest the neuroprotective and therapeutic potential of Tocovid and Twendee-X for AD treatment.
{"title":"Neuroprotective and Therapeutic Effects of Tocovid and Twendee-X on Aβ Oligomer-Induced Damage in the SH-SY5Y Cell Line","authors":"Xiao Hu, T. Yamashita, Haibo Yu, Zhihong Bian, Xinran Hu, Tian Feng, Koh Tadokoro, R. Morihara, K. Abe","doi":"10.1159/000523983","DOIUrl":"https://doi.org/10.1159/000523983","url":null,"abstract":"Background: Alzheimer’s disease (AD) is the most frequent cause of dementia among the elderly. The accumulation of amyloid beta (Aβ) and its downstream pathological events such as oxidative stress play central roles in AD. Recent studies revealed that Aβ oligomer (AβO)-induced strong neurotoxicity in SH-SY5Y cells via the induction of oxidative stress. Objective: In the present study, we investigated the effect of two antioxidants, Tocovid and Twendee-X, on AβO-induced SH-SY5Y cell damage. Methods: AβOs (2.5 μM) were applied to induce cellular damage in the SH-SY5Y cell line. Cell viability following AβO toxicity, Tau protein phosphorylation, cell morphology, and intracellular reactive oxygen species were assayed with or without different concentrations of Tocovid or Twendee-X. Results: Tocovid (60 μg/mL) and Twendee-X (150 μg/mL) significantly recovered cell viability from AβO toxicity (**p < 0.01, vs. control), attenuated Tau protein phosphorylation (**p < 0.01, vs. AβOs), improved cell morphology (**p < 0.01, vs. AβOs), and suppressed intracellular ROS (**p < 0.01, vs. AβOs) in SH-SY5Y cells. Conclusion: These findings suggest the neuroprotective and therapeutic potential of Tocovid and Twendee-X for AD treatment.","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47824200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-12-30DOI: 10.1159/000528875
Robert J Nona, Zhouwei Xu, Gail A Robinson, Robert D Henderson, Pamela A McCombe
Introduction: The aims of the study were to document the characteristics of amyotrophic lateral sclerosis (ALS) patients in Queensland, to examine factors influencing age of onset, and survival, and to study those with early-onset (<45 years) disease and those with long (>5 years) survival.
Methods: We studied subjects seen at the ALS Clinic at the Royal Brisbane and Women's Hospital. We recorded sex, age of onset, region of onset, length of survival, presence of family history, type of disease, and evidence of cognitive involvement. We analysed the influence of these features on age of onset and survival. We analysed the features of patients with early onset of disease and patients with long survival.
Results: There were 855 ALS patients (505 males) in the cohort. The age of onset was lower in males than females, in patients with a family history of ALS compared to those without, and in patients with spinal onset compared to bulbar onset. Early-onset disease was seen in 10% of patients, and had a greater proportion of males, spinal onset, and classical ALS phenotype compared to late-onset disease. Survival was shorter in females, in patients with bulbar onset, and in patients with classical ALS. Long survival was seen in 18% of patients. Patients with long survival had younger age of onset, greater proportion of males, spinal onset, and fewer patients with classical ALS.
Conclusion: Our study confirms that ALS is more prevalent in males and that spinal onset is more common than bulbar onset. Males have earlier onset but longer survival. We found that overall, patients with classical ALS have worse survival than ALS variants, but some patients who were considered to have classical ALS had long survival. This study confirms the similarity of ALS in our region to ALS in other geographical regions.
{"title":"Age of Onset and Length of Survival of Queensland Patients with Amyotrophic Lateral Sclerosis: Details of Subjects with Early Onset and Subjects with Long Survival.","authors":"Robert J Nona, Zhouwei Xu, Gail A Robinson, Robert D Henderson, Pamela A McCombe","doi":"10.1159/000528875","DOIUrl":"10.1159/000528875","url":null,"abstract":"<p><strong>Introduction: </strong>The aims of the study were to document the characteristics of amyotrophic lateral sclerosis (ALS) patients in Queensland, to examine factors influencing age of onset, and survival, and to study those with early-onset (<45 years) disease and those with long (>5 years) survival.</p><p><strong>Methods: </strong>We studied subjects seen at the ALS Clinic at the Royal Brisbane and Women's Hospital. We recorded sex, age of onset, region of onset, length of survival, presence of family history, type of disease, and evidence of cognitive involvement. We analysed the influence of these features on age of onset and survival. We analysed the features of patients with early onset of disease and patients with long survival.</p><p><strong>Results: </strong>There were 855 ALS patients (505 males) in the cohort. The age of onset was lower in males than females, in patients with a family history of ALS compared to those without, and in patients with spinal onset compared to bulbar onset. Early-onset disease was seen in 10% of patients, and had a greater proportion of males, spinal onset, and classical ALS phenotype compared to late-onset disease. Survival was shorter in females, in patients with bulbar onset, and in patients with classical ALS. Long survival was seen in 18% of patients. Patients with long survival had younger age of onset, greater proportion of males, spinal onset, and fewer patients with classical ALS.</p><p><strong>Conclusion: </strong>Our study confirms that ALS is more prevalent in males and that spinal onset is more common than bulbar onset. Males have earlier onset but longer survival. We found that overall, patients with classical ALS have worse survival than ALS variants, but some patients who were considered to have classical ALS had long survival. This study confirms the similarity of ALS in our region to ALS in other geographical regions.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10458930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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