bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase III dose‐comparison study of glatiramer acetate for multiple sclerosis
Authors: Comi Giancarlo , Cohen Jeffrey A. , Arnold Douglas L. , Wynn Daniel , Filippi Massimo ,   for the FORTE Study Group
Published: October 2010

AbstractObjective:To evaluate the safety, tolerability, and efficacy of glatiramer acetate (GA) 40mg compared to a 20mg dose.Methods:Patients with multiple sclerosis (MS) with ≥1 documented relapse in 12 months prior to screening, or ≥2 documented relapses in 24 months prior to screening, and Expanded Disability Status Scale (EDSS) score 0 to 5.5 were enrolled. Patients were evaluated at screening, baseline, and at months 1, 2, 3, 6, 9, and 12. Primary endpoint was rate of confirmed relapses observed during 12‐month study. Analysis was by intent‐to‐treat.Results:A total of 1,155 patients randomized to GA 20mg (n = 586) or 40mg (n = 569). The groups were well‐matched at baseline on demographic, clinical, and magnetic resonance imaging (MRI) characteristics. The primary endpoint was similar in both groups (relative risk [RR] = 1.07; 95% confidence interval [CI], 0.88–1.31; p = 0.486) with mean annualized relapse rates (ARRs) of 0.33 for the 20mg group, 0.35 for the 40mg group, and 0.27 for patients from both groups who completed the entire 1‐year treatment. A total of 77% of patients remained relapse‐free in both groups. Both groups showed a reduction in mean number of gadolinium‐enhancing and new T2 lesions over time with trend for faster reduction in the first trimester with the 40mg dose compared with 20mg dose. Both doses were well‐tolerated with a safety profile similar to that observed in previous studies of 20mg GA.Interpretation:In relapsing‐remitting MS patients, both the currently‐approved GA 20mg and 40mg doses were safe and well‐tolerated, with no gain in efficacy for the higher dose. Ann Neurol 2011;69:75–82.
Mediterranean diet and magnetic resonance imaging–assessed cerebrovascular disease
Authors: Scarmeas Nikolaos , Luchsinger José A. , Stern Yaakov , Gu Yian , He Jing , DeCarli Charlie , Brown Truman , Brickman Adam M. 
Published: October 2010

AbstractObjective:Cerebrovascular disease is 1 of the possible mechanisms of the previously reported relationship between Mediterranean‐type diet (MeDi) and Alzheimer's disease (AD). We sought to investigate the association between MeDi and MRI infarcts.Methods:High‐resolution structural MRI was collected on 707 elderly 65 years or older community residents of New York with available dietary assessments administered an average of 5.8 years (3.22 standard deviations [SDs]) before the MRI. Participants were divided into 3 groups of adherence to MeDi (low, middle, and high tertiles). We examined the association of increasing adherence to MeDi with presence of infarcts on MRI. Models were run without adjustment, adjusted for basic demographic and clinical factors, and adjusted for vascular risk factors.Results:A total of 222 participants had at least 1 infarct. In the unadjusted model, compared to the low adherence group, those in the moderate MeDi adherence group had a 22% reduced odds of having an infarct (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.55–1.14), while participants in the highest MeDi adherence group had a 36% reduced odds (OR, 0.64; 95% CI, 0.42–0.97; p for trend = 0.04). In adjusted models, the association between MeDi adherence and MRI infarcts remained essentially unchanged. The association of high MeDi adherence with infarcts was comparable to that of hypertension (40% reduced probability), did not vary by infarct size or after excluding patients with dementia (n = 46) or clinical strokes (n = 86). There was no association between MeDi and white matter hyperintensities.Interpretation:Higher adherence to the MeDi is associated with reduced cerebrovascular disease burden. Ann Neurol 2011
Apomorphine treatment in Alzheimer mice promoting amyloid‐β degradation
Authors: Himeno Eri , Ohyagi Yasumasa , Ma Linqing , Nakamura Norimichi , Miyoshi Katsue , Sakae Nobutaka , Motomura Kyoko , Soejima Naoko , Yamasaki Ryo , Hashimoto Tetsuya , Tabira Takeshi , M. LaFerla Frank , Kira Jun‐ichi 
Published: October 2010

AbstractObjective:Intracellular amyloid β‐protein (Aβ) contributes to neurodegeneration in Alzheimer disease (AD). Apomorphine (APO) is a dopamine receptor agonist for Parkinson disease and also protects against oxidative stress. Efficacy of APO for an AD mouse model and effects of APO on cell cultures are studied.Methods:The triple transgenic AD mouse model (3xTg‐AD) has 2 familial AD‐related gene mutations (APPKM670/671NL/PS1M146V) and a tau gene mutation (TauP301L). Six‐month‐old 3xTg‐AD mice were treated with subcutaneous injections of APO once a week for 1 month. Memory function was evaluated by Morris water maze before and after the treatment. Brain tissues were examined by immunohistochemical staining and Western blotting. Effects of APO on intracellular Aβ degradation, activity of Aβ‐degrading enzymes, and protection against oxidative stress were studied in cultured SH‐SY5Y cells.Results:After APO treatment, short‐term memory function was dramatically improved. Significant decreases in the levels of intraneuronal Aβ, hyper‐phosphorylated tau (p‐tau), p53, and heme oxygenase‐1 proteins were observed. Moreover, APO promoted degradation of intracellular Aβ, increased activity of proteasome and insulin‐degrading enzyme, protected against H2O2 toxicity, and decreased p53 protein levels in the cultured cells.Interpretation:3xTg‐AD mice show intraneuronal Aβ accumulation and memory disturbances before extracellular Aβ deposition. Our data demonstrating improvement of memory function of 3xTg‐AD mice with decreases in intraneuronal Aβ and p‐tau levels by APO treatment strongly suggest that intraneuronal Aβ is an important therapeutic target and APO will be a novel drug for AD. Ann Neurol 2011
Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl‐11C]‐2‐(4′‐methylaminophenyl)‐ 6‐hydroxybenzothiazole
Authors: Stankoff Bruno , Freeman Leorah , Aigrot Marie‐Stéphane , Chardain Audrey , Dollé Frédéric , Williams Anna , Galanaud Damien , Armand Lucie , Lehericy Stéphane , Lubetzki Catherine , Zalc Bernard , Bottlaender Michel 
Published: October 2010

AbstractObjective:Imaging of myelin tracts in vivo would greatly improve the monitoring of demyelinating diseases such as multiple sclerosis (MS). To date, no imaging technique specifically targets demyelination and remyelination. Recently, amyloid markers related to Congo red have been shown to bind to central nervous system (CNS) myelin. Here we questioned whether the thioflavine‐T derivative 2‐(4′‐methylaminophenyl)‐6‐hydroxybenzothiazole (PIB), which also binds to amyloid plaques, could serve as a myelin marker.Methods:PIB fixation to myelin was studied by fluorescence in the normal and dysmyelinating mouse brain, as well as in the postmortem brain of MS patients. Positron emission tomography (PET) experiments were conducted using [11C]PIB in baboons and in a proof of concept clinical study in 2 MS patients.Results:Applied directly on tissue sections or after intraperitoneal injection, PIB stained CNS myelin, and the decrease in the level of fixation paralleled the amount of myelin loss in a dysmyelinating mutant. In normally myelinated areas of postmortem MS brain, demyelinated and remyelinated lesions were clearly distinguishable by the differential intensity of labeling observed with PIB. PET using intravenously injected radiolabeled [11C]PIB imaged CNS myelin in baboons and humans. In MS patients, the dynamic analysis of PET acquisitions allowed quantitative assessment of demyelination.Interpretation:PIB could be used as an imaging marker to quantify myelin loss and repair in demyelinating diseases. Ann Neurol 2011;
Oxetane als vielseitige Bausteine in der Wirkstoff‐Forschung und Synthese
Authors: Burkhard Johannes A. , Wuitschik Georg , Rogers‐Evans Mark , Müller Klaus , Carreira Erick M. 
Published: October 2010

AbstractErhebliche Geld‐ und Personalressourcen werden jährlich für die Entwicklung neuer Medikamente aufgewendet. Doch trotz verbesserter Techniken, die den Zugang zu unerforschtem chemischem Raum ermöglichen, überwinden nur wenige der neuen Verbindungen die zahlreichen physikochemischen und pharmakologischen Hürden in der Wirkstoff‐Forschung und ‐Entwicklung. Es hat sich gezeigt, dass der Einbau einer Oxetaneinheit in das molekulare Gerüst einer Verbindung deren Eigenschaften wesentlich verbessern kann. Von besonderem Interesse sind dabei Oxetane, die nur in der 3‐Position substituiert sind, da ihr Einbau in ein Molekülgerüst kein neues Stereozentrum erzeugt. Dieser Kurzaufsatz gibt einen Überblick über die jüngsten Fortschritte bei der Herstellung und Verwendung 3‐substituierter Oxetane. Ebenso werden Veränderungen physiko‐ und biochemischer Eigenschaften bei der Einführung einer Oxetaneinheit in Abhängigkeit von der Einbauposition diskutiert.
Kolloidale Organisation: der Weg vom Partikel zu kolloidalen Molekülen und Kristallen
Authors: Li Fan , Josephson David P. , Stein Andreas 
Published: October 2010

AbstractKolloidale Partikel können genau wie Atome (die Bausteine der Moleküle, Makromoleküle und Kristalle) als Baueinheiten für Materialien betrachtet werden. Periodische Anordnungen von Kolloiden – kolloidale Kristalle – haben in den letzten 20 Jahren viel Aufmerksamkeit erregt, im Wesentlichen wegen ihrer einzigartigen photonischen Eigenschaften. Die archetypischen Opalstrukturen beruhen auf dicht gepackten Anordnungen von Kügelchen mit Durchmessern im Submikrometerbereich. Das Interesse an der Strukturierung von Materialien in diesem Größenbereich, aber mit komplexeren Eigenschaften und idealerweise durch Selbstorganisationsprozesse, hat zu großen Fortschritten bei der Kontrolle der Eigenschaften sowohl der Baueinheiten als auch ihrer Anordnungen geführt. Erforderlich dafür sind Kolloide, kolloidale Cluster und kolloidale “Moleküle” mit speziellen Formen und der Fähigkeit zur Bildung einer gerichteten Bindung, eine Kontrolle über kurz‐ und langreichweitige Wechselwirkungen sowie Möglichkeiten zur Positionierung und Orientierung dieser Bausteine. Dieser Aufsatz beleuchtet jüngste experimentelle und theoretische Fortschritte bei der Organisation von Kolloiden mit einer Größe von mehr als 50 nm.
Die Wasserstoffbrücke – eine aktualisierte Definition
Authors: Desiraju Gautam R. 
Published: October 2010

AbstractDie Wasserstoffbrücke ist eine Wechselwirkung, bei der ein Wasserstoffatom von zwei Atomen statt nur einem angezogen wird und als Brücke zwischen den beiden wirkt. Die Anziehung wird mit zunehmender Elektronegativität jedes der beiden Atome stärker. In klassischer Betrachtungsweise sind Wasserstoffbrücken weitgehend elektrostatisch, in manchen Fällen sogar teilkovalent. Das Konzept der Wasserstoffbrücke wurde im Laufe der Zeit immer wieder erweitert, um auch schwächere und dispersivere Wechselwirkungen einzubeziehen, sofern eine gewisse elektrostatische Beschaffenheit der Wechselwirkung gegeben ist. In der Praxis wird eine enorme Vielfalt an sehr starken, starken, mäßig starken, schwachen und sehr schwachen Wasserstoffbrücken beobachtet. Aktuell werden schwache Wasserstoffbrücken mit vielen Fragen der Strukturchemie und der Biologie in Verbindung gebracht. Während starke Wasserstoffbrücken von allen bestehenden Definitionen der Erscheinung erfasst werden, können schwächere zu Problemen bei der Benennung und zu Konflikten mit bestehenden Definitionen führen. Kürzlich wurde der International Union of Pure and Applied Chemistry (IUPAC) eine Empfehlung für eine aktualisierte Definition des Begriffs “Wasserstoffbrücke” vorgelegt. In diesem Essay soll die vorgeschlagene Definition ausführlich erläutert werden.
Colloidal Assembly: The Road from Particles to Colloidal Molecules and Crystals
Authors: Li Fan , Josephson David P. , Stein Andreas 
Published: October 2010

AbstractColloidal particles may be considered as building blocks for materials, just like atoms are the bricks of molecules, macromolecules, and crystals. Periodic arrays of colloids (colloidal crystals) have attracted much interest over the last two decades, largely because of their unique photonic properties. The archetype opal structures are based on close‐packed arrays of spheres of submicrometer diameter. Interest in structuring materials at this length scale, but with more complex features and ideally by self‐assembly processes, has led to much progress in controlling features of both building blocks and assemblies. The necessary ingredients include colloids, colloidal clusters, and colloidal “molecules” which have special shapes and the ability to bind directionally, the control over short‐range and long‐range interactions, and the capability to place and orientate these bricks. This Review highlights recent experimental and theoretical progress in the assembly of colloids larger than 50 nm.
Identification of pollution sources in the Romanian Somes River using graphical analysis of concentration profiles
Authors: Ani Elisabeta‐Cristina , Avramenko Yuri , Kraslawski Andrzej , Agachi Paul Serban 
Published: October 2010

AbstractThe paper describes a method for the identification of pollution sources along a river, based on the analysis of graphical information obtained from long‐term monitoring data. Concentration profiles collected during 2004 at monthly resolution in the Romanian Somes River are employed. The graphical analysis method is based on the comparison of experimental concentration profiles against reference profiles showing concentration evolution along the river after pollutant release. Known nitrate and lead pollution sources along the river were used as reference in order to verify the applicability of the proposed method. Results show that the graphical analysis method enables detection of the majority of sources, and it could be used to investigate the seasonal existence of pollution sources. Moreover, the technique can help guide the definition of the structure of mathematical models for the transport of pollutants in rivers. Copyright © 2010 Curtin University of Technology and John Wiley & Sons, Ltd.
Seasonally tracking vertical and horizontal distribution of unionid mussels (Pronodularia japanensis): implications for agricultural drainage management
Authors: Negishi Junjiro N. , Doi Hideyuki , Katano Izumi , Kayaba Yuichi 
Published: October 2010

Abstract
The vertical and horizontal distribution of unionoid mussels (Pronodularia japanensis) were examined in spring, late summer and winter for different size classes, including juveniles (<20 mm) and large adults (>50 mm), in an agricultural drainage channel in Central Japan.
A large number of small‐sized juveniles were found at the surface (0–3 cm depth) in spring, whereas approximately half of the adults remained in the deep layer (3–8 cm depth). Most individuals were found in the surface layer irrespective of size classes in summer, and approximately 70% of all individuals descended to the deep layer in winter.
Horizontal distribution did not substantially change across seasons and high density patches were consistently found in the areas where substrate appeared to be stable or hydraulically sheltered. Spatial distribution of small juveniles was relatively well predicted by the abundance of adults.
The size–frequency distribution was multi‐modal in three seasons and estimated numbers of newly recruited juveniles were highly variable in recent years, suggesting that juveniles were rarely found owing to irregular reproduction and/or recruitment not the overlooked habitat preferred by small‐sized juveniles.
As P. japanensis is characterized by the behaviour of burrowing down to a depth of ∼10 cm, maintaining the processes of sediment deposition appears to be one of the critical criteria for the conservation of mussel habitats in agricultural drainage channel systems, which are commonly lined with smooth concrete materials. Copyright © 2010 John Wiley & Sons, Ltd.
The value of traditional troughs as freshwater shelters for amphibian diversity
Authors: Garcia‐Gonzalez Claudia , Garcia‐Vazquez Eva 
Published: October 2010

Abstract
Changes in agricultural activities in the Trubia valley (North Iberia, south Europe), mainly substituting husbandry by rural tourism, are modifying trough function: from cattle watering to abandonment or transformation into decorative elements. In the valley, natural ponds are disappearing by desiccation and are scarce or absent.
In the present troughs, constructed by artificial deviation of small streams or fountains, eight amphibian species have been found, representing 57% of the amphibian species recorded in the region. Seven of them were in larval development stages.
Moderate management, presence of sediments in the bottom and abundant floating vegetation were identified as the main factors contributing to amphibian species richness. Trough management significantly correlated with species richness and also with the presence and the genetic population variation of the model species Lissotriton helveticus (palmate newt). Most amphibian species cannot develop in excessively cleaned troughs devoid of vegetation and invertebrates.
In the absence or decline of natural ponds and other water points, traditional troughs can be considered refuges for amphibians. Traditional management actions such as moderate cleaning and protecting vegetation and bottom sediments from these freshwater points are recommended. Promoting the traditional management of troughs is easy and, together with the protection of natural ponds, can help to prevent the decline of amphibian species. Copyright © 2010 John Wiley & Sons, Ltd.
A Novel Terminal Web‐Like Structure in Cortical Lens Fibers: Architecture and Functional Assessment
Authors: Al‐Ghoul Kristin J. , Lindquist Timothy P. , Kirk Spencer S. , Donohue Sean T. 
Published: October 2010

AbstractThis study describes a novel cytoskeletal array in fiber cells of the ocular lens of the rat and shows its relationship to the classical terminal web of other epithelial tissues. Naive adult Sprague‐Dawley rats (n = 28) were utilized. F‐actin, fodrin, myosin IIA, and CP49 distribution was assessed in anterior and posterior polar sections. For functional analysis, lenses were cultured with or without cytochalasin‐D for 3 hr, then processed for confocal microscopy or assessed by laser scan analysis along sutures. Phalloidin labeling demonstrated a dense mesh of F‐actin adjacent to posterior sutural domains to a subcapsular depth of 400 μm. Anterior polar sections revealed a comparable actin structure adjacent to anterior suture branches however, it was not developed in superficial fibers. Fodrin and myosin were localized within the web‐like actin apparatus. The data was used to construct a model showing that the cytoskeletal array is located within the blunt, variable‐width fiber ends that abut at sutures such that the “terminal web” flanks the suture on either side. Treatment with cytochalasin‐D resulted in partial disassembly of the “terminal web” and perturbed cellular organization. Laser scan analysis revealed that cytochalasin‐D treated lenses had significantly greater focal variability than control lenses (P = 0.020). We conclude that cortical fibers of rat lenses contain a bipolar structure that is structurally and compositionally analogous to classical terminal webs. The results indicate that the lens “terminal web” functions to stabilize lens fiber ends at sutures thus minimizing structural disorder, which in turn, promotes the establishment and maintenance of lens transparency. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Intratumoral Lymphatics and Lymphatic Vessel Invasion Detected by D2‐40 Are Essential for Lymph Node Metastasis in Bladder Transitional Cell Carcinoma
Authors: Ma Yong , Hou Youcui , Liu Binghua , Li Xuemei , Yang Shucai , Ma Jing 
Published: October 2010

AbstractBladder cancer is frequently associated with regional lymph node metastasis at the time of diagnosis or after initial treatment, and lymph node metastasis is crucial for clinical therapeutic strategies. Lymphangiogenesis, detected by antibodies specific for lymphatic endothelial cells, is correlated with cancer spread, but the mechanisms that underlie lymphatic spread and the role of lymphangiogenesis in cancer metastasis has been less clear. The aim of this study was to investigate the association of vascular endothelial growth factor (VEGF)‐D expression, intratumoral lymphatics, and lymphatic invasion associated with lymph node metastasis as well as the prognostic analysis in patients with bladder transitional cell carcinoma (TCC). The VEGF‐D expression was evaluated by immunohistochemistry in 72 specimens, and tumoral lymphatic vessels were measured by D2‐40. Counts of lymph vessels were taken in intratumoral and peritumoral areas. Survival analyses and their independent roles were investigated using univariate and multivariate analysis models. The high expression of VEGF‐D was closely associated with the intratumoral lymphatic vessels, tumoral lymphatic invasion, and lymph node metastasis as well as a shorter overall survival. Higher lymphatic vessel density, intratumoral lymphatics, and lymphatic invasion showed a significant association with lymph node metastasis. Univariate analysis indicated that VEGF‐D, intratumoral lymphatics, and lymphatic invasion were associated with overall survival, but they were not independent prognostic factors for bladder TCC in multivariate analysis. We conclude that VEGF‐D plays an essential role in tumoral lymphangiogenesis. Intratumoral lymphatics and lymphatic invasion are important predictive factors of pelvic lymph node metastasis in patients with bladder cancer. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Expressions of Neutrophil Gelatinase‐Associated Lipocalin in Gastric Cancer: A Potential Biomarker for Prognosis and an Ancillary Diagnostic Test
Authors: Wang Hui‐Ju , He Xu‐Jun , Ma Ying‐Yu , Jiang Xiao‐Ting , Xia Ying‐Jie , Ye Zai‐Yuan , Zhao Zhong‐Sheng , Tao Hou‐Quan 
Published: October 2010

AbstractThe aim of this study was to explore the clinical significance of neutrophil gelatinase‐associated lipocalin (NGAL) in the development and prognosis of gastric cancer. NGAL tumor levels were determined in 333 GC patients by immunohistochemistry. NGAL in blood samples from 63 healthy donors and 60 gastric cancer patients were also determined by enzyme‐linked immunosorbent assay. Rate of NGAL expression was correlated with the size of tumor (69.3% in >4 cm tumors vs. 46.1% in ≤4 cm tumors), Lauren's classification (84.3% in diffuse type vs. 28.2% in intestinal type), lymph node metastasis (75.6% vs. 16.4% with no metastasis), vascular invasion (74.9% vs. 26.8% with no invasion), distant metastasis (94.3% vs. 50.3% with no distant metastasis), and TNM stage (81.8% in TNM III+IV vs. 20.5% in TNM I+II). NGAL expression can be used as an independent prognostic factor in gastric cancer as indicated by multivariate analysis. Positivity for serum NGAL was higher than that for carbohydrate antigen determinant, CA19‐9 (38.1% vs. 12.5%) in TNM I, and higher than that for carcinoembryonic antigen, CEA (58.3% vs. 8.3%) and CA19‐9 (58.3% vs. 8.3%) in TNM II. In conclusion, serum NGAL has great potential to be used as an ancillary test for diagnosis of gastric cancer. Increased expression of NGAL in tumors suggests gastric cancer is likely to be at an advanced stage with invasion and metastasis, and also poor prognosis. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.