阿尔茨海默氏病研究进展(英文)Pub Date : 2021-07-14DOI: 10.4236/aad.2021.103003
Y. Okada, N. Ohno, Koji Kariya-city Aichi-pref. Tanaka
{"title":"Correlation between Alzheimer’s Disease and Dementia with Lewy Bodies Scores Using VSRAD Advance","authors":"Y. Okada, N. Ohno, Koji Kariya-city Aichi-pref. Tanaka","doi":"10.4236/aad.2021.103003","DOIUrl":"https://doi.org/10.4236/aad.2021.103003","url":null,"abstract":"The objective of the study was to explore the relationship between the indicators of Alzheimer’s disease and dementia with Lewy bodies using the voxel-based specific regional analysis system for Alzheimer’s Disease (VSRAD) advance. Among 36 patients with suspected dementia, patients with Alzheimer’s disease and dementia with Lewy bodies were identified using VSRAD advance from March 1 to October 30, 2019. All patients underwent brain Magnetic Resonance Imaging (MRI). We diagnosed Alzheimer’s disease using Volume of Interest (VOI) in the Medial Temporal Lobe (MTL) atrophy ratio > 2 and dementia with Lewy bodies using both VOI in the MTL atrophy ratio ≤ 2 and gray/white matter atrophy ratio ≥ 0.2. The correlation between the indicators of Alzheimer’s disease and dementia with Lewy bodies was calculated. The number of patients classified as having Alzheimer’s disease and dementia with Lewy bodies was 25 and 11, respectively. In the Alzheimer’s disease group, the correlation coefficient between the extent of gray matter atrophy and the severity of atrophy in the dorsal brainstem gray matter was r = -0.40 (p = 0.045). In dementia with Lewy bodies group, the correlation coefficient between the extent of gray matter atrophy and the severity of atrophy in the dorsal brainstem white matter was r = -0.78 (p < 0.01). Using VSRAD advance, gray matter atrophy and dorsal brainstem grey/white matter atrophy were found to be negatively correlated in Alzheimer’s disease and dementia with Lewy bodies.","PeriodicalId":57126,"journal":{"name":"阿尔茨海默氏病研究进展(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85874921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
阿尔茨海默氏病研究进展(英文)Pub Date : 2021-06-28DOI: 10.4236/aad.2021.102002
W. Lenderking, C. Abel, E. Brookes, N. Sargalo, Dina Filipenko, Charles Smith, R. Lo
{"title":"Virtual Cognitive Screenings and Interviews of Patients with Neurodegenerative Conditions Associated with Alzheimer’s Disease and Parkinson’s Disease","authors":"W. Lenderking, C. Abel, E. Brookes, N. Sargalo, Dina Filipenko, Charles Smith, R. Lo","doi":"10.4236/aad.2021.102002","DOIUrl":"https://doi.org/10.4236/aad.2021.102002","url":null,"abstract":"The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly referred to as COVID-19, brings myriad challenges to research conducted among those more susceptible to the virus. According to the United States (US) Centers for Disease Control (CDC), eight out of ten re-ported COVID-19 deaths are among people > 65 years of age and older. Nonetheless, researchers must continue the crucial work of investigating and understanding diseases that affect the elderly. The focus of this white paper is to assess the challenges associated with research within the elderly population with neurocognitive conditions. Specifically, this paper addresses the need for the standardized administration of performance measures (e.g., neurocognitive assessments) among a dementia population while ensuring the physical safety of participants. Consideration is given to the administration of performance measures and the availability and feasibility of administering these measures remotely to a population that may have difficulty using novel technologies. In implementing remote research assessments, it is suggested that researchers fol-low a GAMMA approach by: 1) establishing clear Guidance on remote visit expectations and processes; 2) establishing Appropriate exclusionary criteria in the development of the study design; 3) providing subjects Appropriate study Materials for visual processing; 4) incorporating Multiple data sources in the overall study design (e.g., caregiver input); and 5) Acknowledging that there will be study limitations as researchers use emerging technology with this patient population, and using mitigation strategies for these limitations where possible.","PeriodicalId":57126,"journal":{"name":"阿尔茨海默氏病研究进展(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82622688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
阿尔茨海默氏病研究进展(英文)Pub Date : 2021-01-01DOI: 10.4236/aad.2021.104005
Robert Logan, Sabrina S. Zerbey, Sean J. Miller
{"title":"The Future of Artificial Intelligence for Alzheimer’s Disease Diagnostics","authors":"Robert Logan, Sabrina S. Zerbey, Sean J. Miller","doi":"10.4236/aad.2021.104005","DOIUrl":"https://doi.org/10.4236/aad.2021.104005","url":null,"abstract":"Alzheimer’s disease (AD) is a leading cause of death, yet there is no dis-ease-modifying drug therapy currently available. It is critical to establish a diagnosis of AD before clinical system onset so that drug therapies can start earlier. Unfortunately, this is not the current standard practice. Artificial intelligence (AI) holds tremendous promise for identifying AD related structural changes in brain scan images. This paper discusses the recent applications and potential future directions for AI in AD diagnostics. Annual brain scanning and computer vision-assisted early diagnosis is encouraged, so that disease-modifying drug therapy could begin earlier in the progressive pa-thology.","PeriodicalId":57126,"journal":{"name":"阿尔茨海默氏病研究进展(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88569436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
阿尔茨海默氏病研究进展(英文)Pub Date : 2020-07-02DOI: 10.4236/aad.2020.93004
K. Kojima, I. Kawahata, Hisanao Izumi, Sei-Ichi Yoshihara, K. Oki, K. Fukunaga
{"title":"Intranasal Administration of Conditioned Medium from Cultured Mesenchymal Stem Cells Improves Cognitive Impairment in Olfactory Bulbectomized Mice","authors":"K. Kojima, I. Kawahata, Hisanao Izumi, Sei-Ichi Yoshihara, K. Oki, K. Fukunaga","doi":"10.4236/aad.2020.93004","DOIUrl":"https://doi.org/10.4236/aad.2020.93004","url":null,"abstract":"Alzheimer’s disease (AD) is the common cause of \u0000dementia which shows the neuro-pathologies like an accumulation of amyloid-β (Aβ) \u0000and degeneration of cholinergic neuron. Olfactory bulbectomized (OBX) mice show \u0000some of AD features, so they have been used to research as AD model. \u0000Mesenchymal stem cells (MSCs) can differentiate into many kinds of cells, \u0000including neuronal cells. In this study, we intranasally administrated the \u0000conditioned medium derived from cultured umbilical cord (UC) MSCs. The \u0000intranasal administration of the MSCs medium restored the cognitive impairment \u0000observed in OBX mice. In addition, the decreased number of choline \u0000acetyltransferase-positive cells in the medial septum was restored by the \u0000conditioned medium administration. In conclusion, MSCs-derived conditioned \u0000medium may have protective effects of cholinergic neurons in the medial septum, \u0000thereby rescuing the cognitive impairment of OBX.","PeriodicalId":57126,"journal":{"name":"阿尔茨海默氏病研究进展(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76449634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
阿尔茨海默氏病研究进展(英文)Pub Date : 2020-01-01DOI: 10.4236/aad.2020.91001
A. Shata, W. Elkashef, M. Hamouda, H. Eissa
{"title":"Effect of Artesunate vs Memantine in Aluminum Chloride Induced Model of Neurotoxicity in Rats","authors":"A. Shata, W. Elkashef, M. Hamouda, H. Eissa","doi":"10.4236/aad.2020.91001","DOIUrl":"https://doi.org/10.4236/aad.2020.91001","url":null,"abstract":"Alzheimer disease is one of the commonest neurological diseases which is characterized by amyloid plaques accumulation in multiple brain regions. This study investigated the potential neuroprotective effect of artesunate on aluminum induced neurotoxicity vs memantine in rats. 40 male albino Wistar rats were divided randomly into 4 groups as follow: Group 1 negative control, group 2 positive control group induced by ammonium chloride, group 3 rats treated by NH4Cl + artesunate solution, group 4 rats treated by NH4Cl + memantine S.C. spatial Memory and Learning were evaluated using Morris Water Maze (MWM) test. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured in cerebral cortex tissue homogenate. Tumor necrosis factor-α (TNFα) and interleukin-1 beta (IL-1β) concentrations were measured in rat cerebral cortex tissue homogenate using rat enzyme linked immunosorbent assay (ELISA) kits. Real-time quantitative reverse transcription-polymerase chain reaction (Real-time qRT-PCR) for Caspase-3, Bcl-2 and iNOS gene expression was measured in rat cerebral cortex. Slices from cerebral cortex were studied by histopathological examination. Artesunate significantly decreased MDA level and inhibited iNOS, caspase and upregulated Bcl-2 gene expression in cerebral cortex. ART increased significantly antioxidant level GSH, and decreased significantly TNF-alpha and IL-B levels. It reduced significantly 1ry retention latency, 2ry retention latency and initial acquisition latency. It also improved brain histopathology and decreased amyloid plaque deposition. ART exerted neuroprotective effect through oxidative stress correction and enhancement of antiapoptotic markers in neuronal cells of the cerebral cortex.","PeriodicalId":57126,"journal":{"name":"阿尔茨海默氏病研究进展(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83494223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
阿尔茨海默氏病研究进展(英文)Pub Date : 2019-12-30DOI: 10.4236/aad.2019.84004
Fabrice Lele Mutombo, Criss Koba Mjumbe, Isabelle Kasongo Omba, Franck Omangelo Shongo, Nora Mwamini Asani, B. K. Bora
{"title":"State of the Places of Senile Dementia in the Old Hospice of the City of Lubumbashi","authors":"Fabrice Lele Mutombo, Criss Koba Mjumbe, Isabelle Kasongo Omba, Franck Omangelo Shongo, Nora Mwamini Asani, B. K. Bora","doi":"10.4236/aad.2019.84004","DOIUrl":"https://doi.org/10.4236/aad.2019.84004","url":null,"abstract":"The objective of this study was to describe the state of the scene of senile dementia in an intra-institutional environment in the city of Lubumbashi. We conducted a descriptive cross-sectional study, over a period of three months, from February 20 to May 20, 2016. The study population is made up of the residents of the 9 retirement institutions for senior citizens (old people’s home) which counts the city of Lubumbashi. Participation was voluntary with informed consent duly signed by the patient. The probable cases of dementia were detected through the CSI-D and the 5-word test. A predominance of Alzheimer’s was noted (76.92%) and most of them were widowed (69.23%). The mean age of the dementia population was 76.46 ± 9.87 years, while (69.23%) of the patients were out of school. In (23.08%) cases demented patients were male, with a sex ratio of 0.3. Nearly (46.15%) of the demented were drinking. It appears that (69.23%) of the dementias were hypertensive. There are associations between different risk factors and the presence of dementias. Alcohol with an OR (Odd Ratio) = 0.08 (95% CI [0.01 - 0.72], p < 0.05). In our environment, our results indicate a different situation with a much higher prevalence.","PeriodicalId":57126,"journal":{"name":"阿尔茨海默氏病研究进展(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77989586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
阿尔茨海默氏病研究进展(英文)Pub Date : 2019-06-28DOI: 10.4236/AAD.2019.82002
A. Numazawa
{"title":"Suggested Two Hypotheses on Dementia (“Anticholinergic Hypothesis” and “Cranial Skeletal Muscles Hypothesis”) and the Therapeutic Agent","authors":"A. Numazawa","doi":"10.4236/AAD.2019.82002","DOIUrl":"https://doi.org/10.4236/AAD.2019.82002","url":null,"abstract":"The present study was conducted with the objective of further developing the cholinergic hypothesis and not using the prevalent amyloid beta plaque hypothesis or the tau protein hypothesis on dementia. The experiment was conducted on mice using anticholinergic drugs scopolamine and biperiden to investigate the root cause of dementia. First, we measured the mice serum for liquid chromatography-tandem mass spectrometry (LC-MS/MS) after administration of scopolamine and biperiden and found an accumulation of anticholinergic drugs metabolites in the body. The Y-maze test and measurement of LC-MS/MS in the cranial skeletal muscle cells showed that the Scopolamine metabolites have a significant effect on the cranial skeletal muscles, leading to the conclusion that Methocarbamol is an effective treatment for dementia.","PeriodicalId":57126,"journal":{"name":"阿尔茨海默氏病研究进展(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86855477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
阿尔茨海默氏病研究进展(英文)Pub Date : 2019-03-29DOI: 10.4236/AAD.2019.81001
Asmaa Oumellal, M. E. Faris, M. Benabdeljlil
{"title":"Population Normative Data of the Moroccan Arabic Version of Three Components of the 10/66 Dementia Research Group Cognitive Test Battery; with Moroccan Illiterate and Semi-Illiterate Subjects","authors":"Asmaa Oumellal, M. E. Faris, M. Benabdeljlil","doi":"10.4236/AAD.2019.81001","DOIUrl":"https://doi.org/10.4236/AAD.2019.81001","url":null,"abstract":"The aim of this study was to provide normative data of the Moroccan Arabic version of the 10/66 Dementia Research Group cognitive test battery and to explore the effects of age, education/illiteracy, and gender on the performance of these tests. One hundred healthy subjects (67 illiterates and 33 semi-illiterates) participated in this study. None of the participants had serious medical, psychiatric, or neurological disorders including dementia. The protocol included the administration of three components of the 10/66 Dementia Research Group cognitive test battery; Community Screening Instrument for Dementia (CSI “D”, generating the COGSCORE measure of global function), and the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) verbal fluency (VF), word list memory (WLM, immediate recall) tests. All the test scores were not significantly influenced by sex and age. There was no significant effect of education/illiteracy on the CERAD verbal fluency (VF) and Word List Memory (immediate recall) test scores, but a weakly significant (p < 0.05) effect on the CSI “D” COGSCORE performance. These normative data will be useful for clinical interpretations of the three components of the 10/66 Dementia Research Program protocol in illiterate and semi-illiterate Moroccan subjects with cognitive disorders.","PeriodicalId":57126,"journal":{"name":"阿尔茨海默氏病研究进展(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85442841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
阿尔茨海默氏病研究进展(英文)Pub Date : 2019-01-01DOI: 10.4236/aad.2019.83003
J. A. Griffith, S. Northrup, Emma Cieslik, Marie Kelly-Worden
{"title":"Hypoglycemia, Hyperglycemia and Astaxanthin: An in Vitro Alzheimer’s Disease Model","authors":"J. A. Griffith, S. Northrup, Emma Cieslik, Marie Kelly-Worden","doi":"10.4236/aad.2019.83003","DOIUrl":"https://doi.org/10.4236/aad.2019.83003","url":null,"abstract":"Alzheimer’s Disease is projected to increase to 30 million people in the next 30 years and the rate of diabetes mellitus is projected to rise also. Hyperglycemia is commonly observed in patients with diabetes mellitus, and hypoglycemia is a common consequence due to insulin therapy. Previous research has shown a potential link between Alzheimer’s disease and diabetes. This study sought to determine if Astaxanthin (ATX) could prevent mitochondrial dysfunction from the compounded effects of amyloid β (Aβ) plaque and hypoglycemia or hyperglycemia. Growth patterns, ATP production, and ROS generation were examined in 2 μM, 5 μM, 25 μM (hypoglycemic groups), 2 mM, 5 mM (normal groups), and 25 mM glucose (hyperglycemic group), and then treated with or without ATX or Aβ. When hypoglycemia groups and the hyperglycemia group were treated with ATX, their growth patterns were either comparable to control or increased. ATX and Aβ treated cells demonstrated increased growth patterns over cells treated with Aβ alone. Aβ alone treated groups overall had significantly less growth than controls (p β demonstrated low levels of average fluorescence generated by ROS production as determined by MitoSox assay while ATX groups actually produced higher to normal levels of ROS. Cells grown in the presence of Aβ and ATX generally produced more ROS than just Aβ groups. Thus, hypoglycemia and hyperglycemia do appear to compound the effects of Aβ on hippocampal cells. ATX treatment demonstrated promise with increased cellular growth, which promoted usage of ATP by the cell and ROS production. This growth was present even in the presence of Aβ, suggesting that ATX is able to overcome the negative effects of Aβ.","PeriodicalId":57126,"journal":{"name":"阿尔茨海默氏病研究进展(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88734170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
阿尔茨海默氏病研究进展(英文)Pub Date : 2014-06-01DOI: 10.4236/aad.2014.32009
Xiaohua Deng, Meili Li, Weiming Ai, Lixin He, Dahua Lu, Peter R Patrylo, Huaibin Cai, Xuegang Luo, Zhiyuan Li, Xiaoxin Yan
{"title":"Lipolysaccharide-Induced Neuroinflammation Is Associated with Alzheimer-Like Amyloidogenic Axonal Pathology and Dendritic Degeneration in Rats.","authors":"Xiaohua Deng, Meili Li, Weiming Ai, Lixin He, Dahua Lu, Peter R Patrylo, Huaibin Cai, Xuegang Luo, Zhiyuan Li, Xiaoxin Yan","doi":"10.4236/aad.2014.32009","DOIUrl":"10.4236/aad.2014.32009","url":null,"abstract":"<p><p>Chronic neuroinflammation is thought to play an etiological role in Alzheimer's disease (AD), which is characterized pathologically by amyloid and tau formation, as well as neuritic dystrophy and synaptic degeneration. The causal relationship between these pathological events is a topic of ongoing research and discussion. Recent data from transgenic AD models point to a tight spatiotemporal link between neuritic and amyloid pathology, with the obligatory enzyme for <i>β</i>-amyloid (A<i>β</i>) production, namely <i>β</i>-secretase-1 (BACE1), is overexpressed in axon terminals undergoing dystrophic change. However, the axonal pathology inherent with BACE1 elevation seen in transgenic AD mice may be secondary to increased soluble A<i>β</i> in these genetically modified animals. Here we explored the occurrence of the AD-like axonal and dendritic pathology in adult rat brain affected by LPS-induced chronic neuroinflammation. Unilateral intracerebral LPS injection induced prominent inflammatory response in glial cells in the ipsilateral cortex and hippocampal formation. BACE1 protein levels were elevated the ipsilateral hippocampal lysates in the LPS treated animals relative to controls. BACE1 immunoreactive dystrophic axons appeared in the LPS-treated ipsilateral cortex and hippocampal formation, colocalizing with increased <i>β</i>-amyloid precursor protein and A<i>β</i> antibody (4G8) immunolabeling. Quantitative Golgi studies revealed reduction of dendritic branching points and spine density on cortical layer III and hippocampal CA3 pyramidal neurons in the LPS-treated ipsilateral cerebrum. These findings suggest that Alzheimer-like amyloidogenic axonal pathology and dendritic degeneration occur in wildtype mammalian brain in partnership with neuroinflammation following LPS injection.</p>","PeriodicalId":57126,"journal":{"name":"阿尔茨海默氏病研究进展(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211261/pdf/nihms626560.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32784557","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}