bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dorsolateral nigral hyperintensity on 3.0T susceptibility‐weighted imaging in neurodegenerative Parkinsonism
Authors: Reiter Eva , Mueller Christoph , Pinter Bernadette , Krismer Florian , Scherfler Christoph , Esterhammer Regina , Kremser Christian , Schocke Michael , Wenning Gregor K. , Poewe Werner , Seppi Klaus 
Published: March 2015

AbstractBackgroundAbsence of a hyperintense, ovoid area within the dorsolateral border of the otherwise hypointense pars compacta of the substantia nigra (referred to as dorsolateral nigral hyperintensity) on iron‐sensitive high‐field magnetic resonance imaging sequences seems to be a typical finding for patients with Parkinson's disease (PD).ObjectiveThis study was undertaken to evaluate the diagnostic value of the dorsolateral nigral hyperintensity in a cohort of patients with neurodegenerative parkinsonism including PD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) as well as healthy controls using high‐field susceptibility‐weighted imaging (SWI) at 3.0 Tesla (T).MethodsAbsence of dorsolateral nigral hyperintensity was assessed on visual inspection of anonymized 3.0T SWI scans in a case‐control study including 148 patients with neurodegenerative parkinsonism (PD: n = 104; MSA: n = 22; PSP: n = 22) and 42 healthy controls.ResultsDorsolateral nigral hyperintensity was absent unilaterally in all patients with MSA or PSP, in 83 of 90 patients with PD, but only in one of the healthy controls resulting in an overall correct classification of 95.2% in discriminating neurodegenerative parkinsonism from controls in the per‐protocol analysis. Overall correct classification was 93.2% in the intent‐to‐diagnose analysis, including also SWI scans with poor quality (12.1% of all scans) for nigral evaluation.ConclusionVisual assessment of dorsolateral nigral hyperintensity on high‐field SWI scans may serve as a new simple diagnostic imaging marker for neurodegenerative parkinsonian disorders. © 2015 International Parkinson and Movement Disorder Society
Dopamine signals and physiological origin of cognitive dysfunction in Parkinson's disease
Authors: Matsumoto Masayuki 
Published: March 2015

AbstractThe pathological hallmark of Parkinson's disease (PD) is the degeneration of midbrain dopamine neurons. Cognitive dysfunction is a feature of PD patients even at the early stages of the disease. Electrophysiological studies on dopamine neurons in awake animals provide contradictory accounts of the role of dopamine. These studies have established that dopamine neurons convey a unique signal associated with rewards rather than cognitive functions. Emphasizing their role in reward processing leads to difficulty in developing hypothesis as to how cognitive impairments in PD are associated with the degeneration of dopamine circuitry. A hint to resolve this contradiction came from recent electrophysiological studies reporting that dopamine neurons transmit more diverse signals than previously thought. These studies suggest that dopamine neurons are divided into at least two functional subgroups, one signaling “motivational value” and the other signaling “salience.” The former subgroup fits well with the conventional reward theory, whereas the latter subgroup has been shown to transmit signals related to salient but non‐rewarding experiences such as aversive stimulations and cognitively demanding situations. This article reviews recent advances in understanding the non‐reward functions of dopamine, and then discusses the possibility that cognitive dysfunction in PD is at least partially caused by the degeneration of the dopamine neuron subgroup signaling the salience of events in the environment. 2015 International Parkinson and Movement Disorder Society
In vivo neurometabolic profiling in patients with spinocerebellar ataxia types 1, 2, 3, and 7
Authors: Adanyeguh Isaac M. , Henry Pierre‐Gilles , Nguyen Tra M. , Rinaldi Daisy , Jauffret Celine , Valabregue Romain , Emir Uzay E. , Deelchand Dinesh K. , Brice Alexis , Eberly Lynn E. , Öz Gülin , Durr Alexandra , Mochel Fanny 
Published: March 2015

AbstractSpinocerebellar ataxias (SCAs) belong to polyglutamine repeat disorders and are characterized by a predominant atrophy of the cerebellum and the pons. Proton magnetic resonance spectroscopy (1H MRS) using an optimized semiadiabatic localization by adiabatic selective refocusing (semi‐LASER) protocol was performed at 3 T to determine metabolite concentrations in the cerebellar vermis and pons of a cohort of patients with SCA1 (n = 16), SCA2 (n = 12), SCA3 (n = 21), and SCA7 (n = 12) and healthy controls (n = 33). Compared with controls, patients displayed lower total N‐acetylaspartate and, to a lesser extent, lower glutamate, reflecting neuronal loss/dysfunction, whereas the glial marker, myoinositol (myo‐Ins), was elevated. Patients also showed higher total creatine as reported in Huntington's disease, another polyglutamine repeat disorder. A strong correlation was found between the Scale for the Assessment and Rating of Ataxia and the neurometabolites in both affected regions of patients. Principal component analyses confirmed that neuronal metabolites (total N‐acetylaspartate and glutamate) were inversely correlated in the vermis and the pons to glial (myo‐Ins) and energetic (total creatine) metabolites, as well as to disease severity (motor scales). Neurochemical plots with selected metabolites also allowed the separation of SCA2 and SCA3 from controls. The neurometabolic profiles detected in patients underlie cell‐specific changes in neuronal and astrocytic compartments that cannot be assessed by other neuroimaging modalities. The inverse correlation between metabolites from these two compartments suggests a metabolic attempt to compensate for neuronal damage in SCAs. Because these biomarkers reflect dynamic aspects of cellular metabolism, they are good candidates for proof‐of‐concept therapeutic trials. © 2015 International Parkinson and Movement Disorder Society
Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia
Authors: Kancheva Dahlia , Chamova Teodora , Guergueltcheva Velina , Mitev Vanio , Azmanov Dimitar N. , Kalaydjieva Luba , Tournev Ivailo , Jordanova Albena 
Published: March 2015

AbstractBackgroundMutations in TUBB4A have been associated with a spectrum of neurological conditions, ranging from the severe hypomyelination with atrophy of the basal ganglia and cerebellum syndrome to the clinically milder dystonia type 4. The presence of movement abnormalities was considered the common hallmark of these disorders.MethodsClinical, neurological, and neuroimaging examinations, followed by whole exome sequencing and mutation analysis, were performed in a highly consanguineous pedigree with five affected children.ResultsWe identified a novel c.568C>T (p.H190Y) TUBB4A mutation that originated de novo in the asymptomatic mother. The affected subjects presented with an early‐onset, slowly progressive spastic paraparesis of the lower limbs, ataxia, and brain hypomyelination, in the absence of dystonia or rigidity.ConclusionsOur study adds complicated hereditary spastic paraplegia to the clinical spectrum of TUBB4A‐associated neurological disorders. We establish genotype–phenotype correlations with mutations located in the same region in the tertiary structure of the protein. © 2015 International Parkinson and Movement Disorder Society
Dopaminergic regulation of olfactory type G‐protein α subunit expression in the striatum
Authors: Ruiz‐DeDiego I. , Naranjo J.R. , Hervé D. , Moratalla R. 
Published: March 2015

AbstractBackgroundIn rodents, the olfactory type G‐protein α subunit (Gαolf) couples the dopamine D1 receptor (D1R) to adenylyl cyclase, triggering intracellular signaling and neuronal activation. In the striatum, Gαolf is enriched in the striosomes. Changes in Gαolf protein levels have been observed after dopamine depletion. However, the regulation of Gαolf expression by dopamine and dopamine receptors is not fully understood.MethodsTo address this, Striatal Gαolf expression pattern was studied in wild‐type and genetically engineered mice lacking D1R, D2R (D2 receptor), and downstream regulatory element antagonist modulator (DREAM) protein whose dopamine levels were manipulated. Dopamine depletion was accomplished by 6‐hydroxydopamine (6‐OHDA) or by Pitx3 ablation, and dopamine replacement by chronic levodopa (l‐dopa). The Gαolf levels were analyzed by immunohistochemistry, Western blot, and real‐time quantitative polymerase chain reaction (RT‐qPCR).ResultsOur results demostrate that Dopamine depletion or inactivation of D1R abolished the striosomal pattern of Gαolf expression and increased Gαolf protein levels. Dopamine replacement in wild‐type lesioned mice reestablished both the expression pattern and protein levels, but paradoxically increased Gαolf messenger RNA (mRNA). In D1R‐/‐ mice, dopamine depletion decreased striatal Gαolf expression, whereas l‐dopa did not restore either Gαolf levels or its expression pattern. Inactivation of D2R or changes in the cAMP/PKA signaling pathway downstream of Gαolf did not modify its expression.ConclusionOur results show a homeostatic, negative regulation of Gαolf by dopamine and by D1R stimulation, which are also required for the striosomal Gαolf pattern. These results shed light on the regulation of Gαolf by dopamine signaling that could be involved in the pathophysiology of the maladaptive response to chronic l‐dopa treatment in Parkinson's disease. © 2015 International Parkinson and Movement Disorder Society
Automated Neuromelanin Imaging as a Diagnostic Biomarker for Parkinson's Disease
Authors: Castellanos Gabriel , Fernández‐Seara María A. , Lorenzo‐Betancor Oswaldo , Ortega‐Cubero Sara , Puigvert Marc , Uranga Javier , Vidorreta Marta , Irigoyen Jaione , Lorenzo Elena , Muñoz‐Barrutia Arrate , Ortiz‐de‐Solorzano Carlos , Pastor Pau , Pastor María A. 
Published: March 2015

ABSTRACTBackgroundWe aimed to analyze the diagnostic accuracy of an automated segmentation and quantification method of the SNc and locus coeruleus (LC) volumes based on neuromelanin (NM)‐sensitive MRI (NM‐MRI) in patients with idiopathic (iPD) and monogenic (iPD) Parkinson's disease (PD).MethodsThirty‐six patients (23 idiopathic and 13 monogenic PARKIN or LRRK2 mutations) and 37 age‐matched healthy controls underwent 3T‐NM‐MRI. SNc and LC volumetry were performed using fully automated multi‐image atlas segmentation. The diagnostic performance to differentiate PD from controls was measured using the area under the curve (AUC) and likelihood ratios based on receiver operating characteristic (ROC) analyses.ResultsWe found a significant reduction of SNc and LC volumes in patients, when compared to controls. ROC analysis showed better diagnostic accuracy when using SNc volume than LC volume. Significant differences between ipsilateral and contralateral SNc volumes, in relation to the more clinically affected side, were found in patients with iPD (P = 0.007). Contralateral atrophy in the SNc showed the highest power to discriminate PD subjects from controls (AUC, 0.93‐0.94; sensitivity, 91%–92%; specificity, 89%; positive likelihood ratio: 8.4‐8.5; negative likelihood ratio: 0.09‐0.1 at a single cut‐off point). Interval likelihood ratios for contralateral SNc volume improved the diagnostic accuracy of volumetric measurements.ConclusionSNc and LC volumetry based on NM‐MRI resulting from the automated segmentation and quantification technique can yield high diagnostic accuracy for differentiating PD from health and might be an unbiased disease biomarker. © 2015 International Parkinson and Movement Disorder Society
NonmotorSymptoms inSubjectsWithoutEvidence ofDopaminergicDeficits
Authors: Sprenger Fabienne S. , Seppi Klaus , Djamshidian Atbin , Reiter Eva , Nocker Michael , Mair Katherina , Göbel Georg , Poewe Werner 
Published: March 2015

ABSTRACTBackgroundA subgroup of patients initially diagnosed with Parkinson's disease (PD) turn out to have normal dopamine transporter single‐photon emission computed tomography imaging and have been labeled as subjects without evidence of dopaminergic deficit (SWEDDs). In this study, we sought to further characterize these patients and have analyzed the frequency of nonmotor symptoms (NMS) in SWEDDs, PD patients, and healthy controls.MethodsWe analyzed the baseline clinical data of 412 PD patients, 184 controls, and 62 SWEDDs included in the Parkinson's Progression Marker Initiative study on a variety of different NMS questionnaires.ResultsBoth PD patients and SWEDDs had greater frequency of NMS than healthy controls. Furthermore, some NMS, such as orthostatic hypotension as well as cardiovascular and thermoregulatory dysfunction were even more commonly reported in SWEDDs than in PD patients, whereas hyposmia was more common in PD, compared to SWEDDs.ConclusionNMS are more frequent in SWEDDs than in controls, and autonomic dysfunction and orthostatic hypotension were even more common than in PD patients. These findings support the notion that SWEDDS represent a group of patients with still poorly understood pathophysiology. © 2015 International Parkinson and Movement Disorder Society
Conditions of kimberlite magma generation: experimental constraints
Authors: Sokol A.G. , Kruk A.N. 
Published: March 2015

Abstract
Melting and multiple saturation experiments with systems simulating primary kimberlite magma compositions at 5.5–6.5 GPa provide constraints on magma generation conditions. The liquidus of model kimberlitic systems exceeds the hottest temperatures of lithospheric mantle (1400 °C) but is 150–200 °C lower in systems with lower CO2/(CO2 + H2O) ratios. The high melting points require additional heat sources for the generation of kimberlite magmas. Multiple saturation of experimental melts and the stability of individual near-liquidus phases depend on both major-element contents and XCO2 (as the CO2/(CO2 + H2O) molar ratio) in the starting composition. Generally, olivine-bearing assemblages are stable at XCO2 &lt; 0.5, while an increase in MgO/CaO from 1.8 to &gt; 4.0 leads to progressive changes in the equilibrium assemblages: Ol + Grt + Cpx → Ol + Grt + Opx + Cpx → Ol + Grt + Opx. The results of geochemical reconstructions and multiple saturation experiments indicate partial or complete wehrlitization of the kimberlitic source regions. Most of primary magmas with XCO2 &lt; 0.5 may have been derived from carbonated garnet lherzolite. Some highly calcic (MgO/CaO &lt; 2) magmas with XCO2 &lt; 0.5 likely originated from carbonated garnet wehrlite. A probable scenario is that melts and/or fluids repeatedly metasomatized and oxidized the protolith (caused its carbonation and phlogopitization) and thus provided conditions for buffering CO2 and H2O fugacities in the forming kimberlitic magma, at least early in the melting history. During later magma generation, water was, likely, extracted from nominally anhydrous minerals having hydrated (OH) defects in the structure.
LBIBCell: a cell-based simulation environment for morphogenetic problems
Authors: Tanaka Simon , Sichau David , Iber Dagmar 
Published: March 2015

Abstract
Motivation: The simulation of morphogenetic problems requires the simultaneous and coupled simulation of signalling and tissue dynamics. A cellular resolution of the tissue domain is important to adequately describe the impact of cell-based events, such as cell division, cell–cell interactions and spatially restricted signalling events. A tightly coupled cell-based mechano-regulatory simulation tool is therefore required.
Results: We developed an open-source software framework for morphogenetic problems. The environment offers core functionalities for the tissue and signalling models. In addition, the software offers great flexibility to add custom extensions and biologically motivated processes. Cells are represented as highly resolved, massless elastic polygons; the viscous properties of the tissue are modelled by a Newtonian fluid. The Immersed Boundary method is used to model the interaction between the viscous and elastic properties of the cells, thus extending on the IBCell model. The fluid and signalling processes are solved using the Lattice Boltzmann method. As application examples we simulate signalling-dependent tissue dynamics.
Availability and implementation: The documentation and source code are available on http://tanakas.bitbucket.org/lbibcell/index.html
Contact: simon.tanaka@bsse.ethz.ch or dagmar.iber@bsse.ethz.ch
Supplementary information: Supplementary data are available at Bioinformatics online.
Modelling the redshift-space three-point correlation function in SDSS-III
Authors: Guo Hong , Zheng Zheng , Jing Y. P. , Zehavi Idit , Li Cheng , Weinberg David H. , Skibba Ramin A. , Nichol Robert C. , Rossi Graziano , Sabiu Cristiano G. , Schneider Donald P. , McBride Cameron K. 
Published: March 2015

Abstract
We present the measurements of the redshift-space three-point correlation function (3PCF) for z ∼ 0.5 luminous red galaxies of the CMASS sample in the Sloan Digital Sky Survey-III Baryon Oscillation Spectroscopic Survey Data Release 11. The 3PCF measurements are interpreted within the halo occupation distribution framework using high-resolution N-body simulations, and the model successfully reproduces the 3PCF on scales larger than 1 h−1 Mpc. As with the case for the redshift-space two-point correlation functions, we find that the redshift-space 3PCF measurements also favour the inclusion of galaxy velocity bias in the model. In particular, the central galaxy in a halo is on average in motion with respect to the core of the halo. We discuss the potential of the small-scale 3PCF to tighten the constraints on the relation between galaxies and dark matter haloes and on the phase-space distribution of galaxies.
Convection and convective overshooting in stars more massive than 10 M⊙
Authors: Jin Jie , Zhu Chunhua , Lü Guoliang 
Published: March 2015

Abstract
We examine how the mixing length parameter αp and the overshooting parameter δov affect the properties of convective cores and convective envelopes in stars more massive than 10 M⊙. First, we show that a larger value of αp leads to a stronger mixing, a smaller chemical gradient, a higher effective temperature, and a smaller stellar radius. We then find that if a star develops convective core overshooting during the main sequence phase, the star will enter the red (super)giant phase earlier than a star without core overshooting. Finally, we find that a convective envelope leads to a discontinuity of the hydrogen profile above the hydrogen burning shell. Convective envelope overshooting can facilitate the occurrence of blue loop in the Hertzsprung–Russell diagram.
Multimedia Exercise Training Program Improves Distance Walked, Heart Rate Recovery, and Self-efficacy in Cardiac Surgery Patients
Authors: Wang Li-Wei , Ou Shu-Hua , Tsai Chien-Sung , Chang Yue-Cune , Kao Chi-Wen 
Published: March 2015

Background:
Patient education has been shown to be more effective when delivered using multimedia than written materials. However, the effects of using multimedia to assist patients in cardiac rehabilitation have not been investigated.

Objective:
The purpose of this study is to examine the effect of an inpatient multimedia exercise training program on distance walked in the 6-minute walking test (6MWT), heart rate recovery, and walking self-efficacy of patients who had undergone heart surgery.

Methods:
For this longitudinal quasi-experimental study, 60 consecutive patients were assigned to an experimental (n = 20; inpatient multimedia exercise training program) or control (n = 40; routine care) group. Data were collected at 3 times (before surgery, 1 to 2 days before hospital discharge, and 1 month after hospital discharge) and analyzed with the generalized estimating equation approach.

Results:
Most subjects were men (66.7%), had a mean age of 61.32 ± 13.4 years and left ventricular ejection fraction of 56.96% ± 13.28%, and underwent coronary artery bypass graft surgery (n = 34, 56.7%). Subjects receiving the exercise training program showed significantly greater improvement than those in the control group in the 6MWT walking distance (P < .001), heart rate recovery (P = .04), and self-efficacy (P = .002) at hospital discharge. Furthermore, the intervention effects on 6MWT distance (P < .001) and self-efficacy (P < .001) were sustained at 1 month after hospital discharge.

Conclusion:
Our inpatient multimedia exercise training program safely improved distance walked in the 6MWT, heart rate recovery, and self-efficacy at hospital discharge in patients after heart surgery and maintained their improvement in 6MWT and self-efficacy 1 month later.
The Spatial Mixing of Genomes in Secondary Contact Zones
Authors: Sedghifar Alisa , Brandvain Yaniv , Ralph Peter , Coop Graham 
Published: March 2015

AbstractRecent genomic studies have highlighted the important role of admixture in shaping genome-wide patterns of diversity. Past admixture leaves a population genomic signature of linkage disequilibrium (LD), reflecting the mixing of parental chromosomes by segregation and recombination. The extent of this LD can be used to infer the timing of admixture. However, the results of inference can depend strongly on the assumed demographic model. Here, we introduce a theoretical framework for modeling patterns of LD in a geographic contact zone where two differentiated populations are diffusing back together. We derive expressions for the expected LD and admixture tract lengths across geographic space as a function of the age of the contact zone and the dispersal distance of individuals. We develop an approach to infer age of contact zones using population genomic data from multiple spatially sampled populations by fitting our model to the decay of LD with recombination distance. We use our approach to explore the fit of a geographic contact zone model to three human population genomic datasets from populations along the Indonesian archipelago, populations in Central Asia and populations in India.
Detecting hidden diversification shifts in models of trait-dependent speciation and extinction
Authors: Beaulieu Jeremy M , O’Meara Brian C 
Published: March 2015

AbstractThe distribution of diversity can vary considerably from clade to clade. Attempts to understand these patterns often employ state-dependent speciation and extinction models to determine whether the evolution of a particular novel trait has increased speciation rates and/or decreased their extinction rates. It is still unclear, however, whether these models are uncovering important drivers of diversification, or whether they are simply pointing to more complex patterns involving many unmeasured and co-distributed factors. Here we describe an extension to the popular state-dependent speciation and extinction models that specifically accounts for the presence of unmeasured factors that could impact diversification rates estimated for the states of any observed trait, addressing at least one major criticism of BiSSE methods. Specifically, our model, which we refer to as HiSSE (Hidden-State Speciation and Extinction), assumes that related to each observed state in the model are “hidden” states that exhibit potentially distinct diversification dynamics and transition rates than the observed states in isolation. We also demonstrate how our model can be used as character-independent diversification (CID) models that allow for a complex diversification process that is independent of the evolution of a character. Under rigorous simulation tests and when applied to empirical data, we find that HiSSE performs reasonably well, and can at least detect net diversification rate differences between observed and hidden states and detect when diversification rate differences do not correlate with the observed states. We discuss the remaining issues with state-dependent speciation and extinction models in general, and the important ways in which HiSSE provides a more nuanced understanding of trait-dependent diversification.