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Ming Hao, Stephen H Bryant, Yanli Wang
BACKGROUND: Fast and accurate identification of potential drug candidates against therapeutic targets (i.e., drug-target interactions, DTIs) is a fundamental step in the early drug discovery process. However, experimental determination of DTIs is time-consuming and costly, especially for testing the associations between the entire chemical and genomic spaces. Therefore, computationally efficient algorithms with accurate predictions are required to achieve such a challenging task. In this work, we design a new chemoinformatics approach derived from neighbor-based collaborative filtering (NBCF) to infer potential drug candidates for targets of interest...
October 11, 2018: Journal of Cheminformatics
Mahsa Dadar, Yashar Zeighami, Yvonne Yau, Seyed-Mohammad Fereshtehnejad, Josefina Maranzano, Ronald B Postuma, Alain Dagher, D Louis Collins
White Matter Hyperintensities (WMHs) are associated with cognitive decline in aging and Alzheimer's disease. However, the pathogenesis of cognitive decline in Parkinson's disease (PD) is not as clearly related to vascular causes, and therefore the role of WMHs as a marker of small-vessel disease (SVD) in PD is less clear. Currently, SVD in PD is assessed and treated independently of the disease. However, if WMH as the major MRI sign of SVD has a higher impact on cognitive decline in PD patients than in healthy controls, vascular pathology needs to be assessed and treated with a higher priority in this population...
September 27, 2018: NeuroImage: Clinical
Eleonora Fiorenzato, Roberta Biundo, Diego Cecchin, Anna Chiara Frigo, Jinhee Kim, Luca Weis, Antonio P Strafella, Angelo Antonini
BACKGROUND: The pathological processes underlying cognitive impairment in Parkinson's disease (PD) are heterogeneous and the contribution of cerebral amyloid deposits is poorly defined, particularly in the early stages of the disease. OBJECTIVE: To investigate regional [18F]florbetaben binding to amyloid-β (Aβ) and its contribution to cognitive dysfunction in early stage PD. METHODS: A multicenter cohort of 48 PD patients from the Parkinson's Progression Marker Initiative (PPMI) underwent [18F]florbetaben positron emission tomography (PET) scanning...
September 26, 2018: Journal of Alzheimer's Disease: JAD
Ryul Kim, Jin-Sun Jun
While the involvement of the central and peripheral autonomic networks is thought to play an integral role in the development of autonomic symptoms in Parkinson's disease (PD), there is little evidence for an association between autonomic symptoms and striatal dopaminergic depletion. We compared dopamine transporter activity in striatal subregions with various autonomic symptoms covered by the SCOPA-AUT domains including gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, and sexual symptoms in 418 untreated patients with PD...
September 15, 2018: Autonomic Neuroscience: Basic & Clinical
Amir Ashraf-Ganjouei, Alireza Majd, Ali Javinani, Mohammad Hadi Aarabi
Background: Autonomic dysfunction (AD) is one of the non-motor features of Parkinson's disease (PD). Some symptoms tend to occur in the early stages of PD. AD also has a great impact on patient's quality of life. In this study, we aimed to discover the association between AD (Scales for Outcomes in Parkinson's disease-Autonomic, SCOPA-AUT) and microstructural changes in white matter tracts in drug-naïve early PD patients to elucidate the central effects of autonomic nervous system impairments...
2018: PeerJ
Amanda Kenny, Boris Bizumic, Kathleen M Griffiths
BACKGROUND: Although there is a substantial body of research on the stigma associated with mental illness, much of the extant research has not explicitly focused on the concept of prejudice, which drives discriminatory behaviour. Further, research that has investigated prejudice towards people with mental illness has conceptual, theoretical and psychometric limitations. To address these shortcomings, we sought to develop a new measure, the Prejudice towards People with Mental Illness (PPMI) scale, based on an improved conceptualisation and integration of the stigma and prejudice areas of research...
September 12, 2018: BMC Psychiatry
B S Manjunatha, Sangeeta Paul, Chetana Aggarwal, S Bandeppa, V Govindasamy, Ajinath S Dukare, Maheshwar S Rathi, C T Satyavathi, K Annapurna
Genetic and functional diversity of osmotolerant bacterial endophytes colonizing the root, stem, and leaf tissues of pearl millet genotypes differing in their drought susceptibility was assessed. Two genotypes of pearl millet, viz., the drought tolerant genotype TT-1 and the drought susceptible genotype PPMI-69, were used in the present study. Diazotrophs were found to be the predominant colonizers, followed by the Gram positive bacteria in most of the tissues of both the genotypes. Higher proportion of bacterial endophytes obtained from the drought tolerant genotype was found to be osmotolerant...
September 12, 2018: Microbial Ecology
Haijun Lei, Zhongwei Huang, Feng Zhou, Ahmed Elazab, Ee-Leng Tan, Hancong Li, Jing Qin, Baiying Lei
Parkinson's disease (PD) is a neurodegenerative progressive disease that mainly affects the motor systems of patients. To slow this disease deterioration, early and accurate diagnosis of PD is an effective way, which alleviates mental and physical sufferings by clinical intervention. In this paper, we propose a joint regression and classification framework for PD diagnosis via magnetic resonance and diffusion tensor imaging data. Specifically, we devise a unified multi-task feature selection model to explore multiple relationships among features, samples, and clinical scores...
September 3, 2018: IEEE Journal of Biomedical and Health Informatics
Jared T Hinkle, Kate Perepezko, Kelly A Mills, Zoltan Mari, Ankur Butala, Ted M Dawson, Alexander Pantelyat, Liana S Rosenthal, Gregory M Pontone
BACKGROUND: Constipation is a prodromal feature of Parkinson's disease (PD) and the gastrointestinal (GI) tract is implicated in the pathogenesis of PD. However, no studies have demonstrated ante-mortem relationships between nigrostriatal dysfunction and GI dysautonomia in PD. METHODS: The Scale for Outcomes in Parkinson's disease for Autonomic Symptoms (SCOPA-AUT) assesses dysautonomia in the multi-center Parkinson's Progression Marker Initiative (PPMI). We used linear mixed-effects models and reliable change indices (RCIs) to examine longitudinal associations between dysautonomia and dopamine transporter (DAT) striatal binding ratios (SBRs) measured by single-photon emission computerized tomography in PPMI participants over four years (n = 397 at baseline)...
August 22, 2018: Parkinsonism & related Disorders
Lana M Chahine, Liz Urbe, Chelsea Caspell-Garcia, Dag Aarsland, Roy Alcalay, Paolo Barone, David Burn, Alberto J Espay, Jamie L Hamilton, Keith A Hawkins, Shirley Lasch, James B Leverenz, Irene Litvan, Irene Richard, Andrew Siderowf, Christopher S Coffey, Tanya Simuni, Daniel Weintraub
INTRODUCTION: Several characteristics associated with increased risk for Parkinson's disease (PD) have been identified, including specific genotypes and various non-motor symptoms. Characterizing non-motor features, such as cognitive abilities, among individuals considered at-risk for PD is essential to improving prediction of future neurodegeneration. METHODS: Participants belonging to the following cohorts of the Parkinson Progression Markers Initiative (PPMI) study were included: de novo PD with dopamine transporter binding deficit (n = 423), idiopathic REM sleep behavior disorder (RBD, n = 39), hyposmia (n = 26) and non-PD mutation carrier (NMC; Leucine-rich repeat kinase 2 (LRRK2) G2019S (n = 88) and glucocerebrosidase (GBA) gene (n = 38) mutations))...
2018: PloS One
Howard E Morgan, Christina R Ledbetter, Christopher Ferrier, Richard M Zweig, Elizabeth A Disbrow
BACKGROUND: Depression is a common comorbidity of Parkinson's disease (PD); however, the impact of antidepressant status on cortical function in parkinsonian depression is not fully understood. While studies of resting state functional MRI in major depression have shown that antidepressant treatment affects cortical connectivity, data on connectivity and antidepressant status in PD is sparse. OBJECTIVE: We tested the hypothesis that cortico-limbic network (CLN) resting state connectivity is abnormal in antidepressant-treated parkinsonian depression...
2018: Journal of Parkinson's Disease
Darko Aleksovski, Dragana Miljkovic, Daniele Bravi, Angelo Antonini
INTRODUCTION: Discrete patterns of progression have been suggested for patients with Parkinson disease and presenting tremor dominant (TD) or postural instability gait disorders (PIGD). However, longitudinal prospective assessments need to take into consideration the variability in clinical manifestations and the evidence that only 40% of initially classified PIGD remain in this subtype at subsequent visits. METHODS: We analyzed clinical progression of PIGD compared to TD using longitudinal clinical data from the PPMI...
August 14, 2018: Neurological Sciences
Lubin Gou, Wei Zhang, Chuanming Li, Xinlin Shi, Zhiming Zhou, Weijia Zhong, Ting Chen, Xiajia Wu, Chun Yang, Dajing Guo
Purpose: Depression is common in Parkinson's disease (PD) and is correlated with the severity of motor deficits and quality of life. The present study aimed to investigate alterations in the structural brain network related to depression in Parkinson's disease (d-PD) and their correlations with structural impairments of white matter (WM). Materials and Methods: Data were acquired from the Parkinson Progression Markers Initiative (PPMI) database. A total of 84 de novo and drug-naïve PD patients were screened and classified into two groups according to the 15-item Geriatric Depression Scale (GDS-15): d-PD ( n = 28) and nondepression in PD (nd-PD, n = 56)...
2018: Frontiers in Neurology
Samuel Iddi, Dan Li, Paul S Aisen, Michael S Rafii, Irene Litvan, Wesley K Thompson, Michael C Donohue
Parkinson's disease is the second most common neurological disease and affects about 1% of persons over the age of 60 years. Due to the lack of approved surrogate markers, confirmation of the disease still requires postmortem examination. Identifying and validating biomarkers are essential steps toward improving clinical diagnosis and accelerating the search for therapeutic drugs to ameliorate disease symptoms. Until recently, statistical analysis of multicohort longitudinal studies of neurodegenerative diseases has usually been restricted to a single analysis per outcome with simple comparisons between diagnostic groups...
August 8, 2018: Neuro-degenerative Diseases
Mahsa Dolatshahi, Shayan Pourmirbabaei, Aida Kamalian, Amir Ashraf-Ganjouei, Mehdi Yaseri, Mohammad H Aarabi
Background: Parkinson's disease (PD) is characterized by proteinopathies and these proteinopathies seem to interact synergistically and lead to protein aggregations and changes in protein cerebrospinal fluid (CSF) levels. In this study, we aimed to explore the longitudinal changes of CSF a lpha-synuclein (α-syn), total tau (t-tau), phosphorylated tau (p-tau), and beta-amyloid (Aβ1-42 ) and their relationships with each other and with baseline clinical entities like REM sleep behavior disorder (RBD), cognitive impairment, motor symptoms, and olfaction dysfunction...
2018: Frontiers in Neurology
Alberto Llera, Ismael Huertas, Pablo Mir, Christian F Beckmann
PURPOSE: Differences in site, device, and/or settings may cause large variations in the intensity profile of dopamine transporter (DAT) single-photon emission computed tomography (SPECT) images. However, the current standard to evaluate these images, the striatal binding ratio (SBR), does not efficiently account for this heterogeneity and the assessment can be unequivalent across distinct acquisition pipelines. In this work, we present a voxel-based automated approach to intensity normalize such type of data that improves on cross-session interpretation...
July 9, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Sue-Jin Lin, Tobias R Baumeister, Saurabh Garg, Martin J McKeown
The clinicopathological correlations between aspects of cognition, disease severity and imaging in Parkinson's Disease (PD) have been unclear. We studied cognitive profiles, demographics, and functional connectivity patterns derived from resting-state fMRI data (rsFC) in 31 PD subjects from the Parkinson's Progression Markers Initiative (PPMI) database. We also examined rsFC from 19 healthy subjects (HS) from the Pacific Parkinson's Research Centre. Graph theoretical measures were used to summarize the rsFC patterns...
2018: Frontiers in Neurology
G D'Ancona, M Dißmann, H Heinze, D Zohlnhöfer-Momm, H Ince, S Kische
OBJECTIVES: To report our experience with the recently introduced 34 mm Evolut transcatheter aortic valve replacement (TAVR) prosthesis. BACKGROUND: A larger TAVR prosthesis has become available for the treatment of aortic stenosis (AVS) in larger native aortic annuli (up to 30 mm). Outcomes with this new device are still unreported. RESULTS: The first 25 transfemoral TAVRs performed by our team with the self-expandable 34 mm Evolut are presented...
August 2018: Netherlands Heart Journal
Christoph B Olivier, Vandana Sundaram, Deepak L Bhatt, Sergio Leonardi, Renato D Lopes, Victoria Y Ding, Lingyao Yang, Gregg W Stone, Ph Gabriel Steg, C Michael Gibson, Christian W Hamm, Matthew J Price, Harvey D White, Manisha Desai, Donald R Lynch, Robert A Harrington, Kenneth W Mahaffey
BACKGROUND: Controversies exist over the appropriate definition for peri-procedural myocardial infarction (PPMI) and its association with mortality. This study aims to evaluate one-year survival following percutaneous coronary intervention (PCI) and the association of different definitions of PPMI with survival among patients with stable angina (SA) or acute coronary syndrome (ACS) in the contemporary era. METHODS: We used data from the CHAMPION PLATFORM and CHAMPION PCI trials of patients undergoing PCI and conducted univariable and multivariable Cox proportional hazard regression models to evaluate mortality risk during the first year after PCI...
November 1, 2018: International Journal of Cardiology
Ozkan Cigdem, Iman Beheshti, Hasan Demirel
Three-dimensional magnetic resonance imaging (3D-MRI) has been effectively used in the diagnosis of progressive neurodegenerative diseases including Parkinson's disease (PD). Pre-processing of 3D-MRI scans plays an important role for post-processing. In this paper, voxel-based morphometry (VBM) technique is used to compare morphological dierences of PDs versus healthy controls (HCs) in gray matter (GM) and white matter (WM). The effects of using different covariates (i.e. total intracranial volume (TIV), age, sex and combination of them) as well as two different hypotheses, t-contrast and f-contrast, on classification of PD from HCs have been studied...
August 1, 2018: Computers in Biology and Medicine
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