bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized double‐blind, placebo‐controlled trial of venlafaxine‐extended release for co‐occurring cannabis dependence and depressive disorders
Authors: Levin Frances R. , Mariani John , Brooks Daniel J. , Pavlicova Martina , Nunes Edward V. , Agosti Vito , Bisaga Adam , Sullivan Maria A. , Carpenter Kenneth M. 
Published: January 2013

AbstractAimTo evaluate whether venlafaxine‐extended release (VEN‐XR) is an effective treatment for cannabis dependence with concurrent depressive disorders.DesignThis was a randomized, 12‐week, double‐blind, placebo‐controlled trial of out‐patients (n = 103) with DSM‐IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN‐XR on a fixed‐flexible schedule or placebo. All patients received weekly individual cognitive–behavioral psychotherapy that primarily targeted marijuana use.SettingsThe trial was conducted at two university research centers in the United States.ParticipantsOne hundred and three cannabis‐dependent adults participated in the trial.MeasurementsThe primary outcome measures were (i) abstinence from marijuana defined as at least two consecutive urine‐confirmed abstinent weeks and (ii) improvement in depressive symptoms based on the Hamilton Depression Rating Scale.FindingsThe proportion of patients achieving a clinically significant mood improvement (50% decrease in Hamilton Depression score from baseline) was high and did not differ between groups receiving VEN‐XR (63%) and placebo (69%) (χ12 = 0.48, P = 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN‐XR (11.8%) compared to placebo (36.5%) (χ12 = 7.46, P < 0.01; odds ratio = 4.51, 95% confidence interval: 1.53, 13.3). Mood improvement was associated with reduction in marijuana use in the placebo group (F1,179 = 30.49, P < 0.01), but not the VEN‐XR group (F1,186 = 0.02, P = 0.89).ConclusionsFor depressed, cannabis‐dependent patients, venlafaxine‐extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use.
Molecular regulation of GABAergic neuron differentiation and diversity in the developing midbrain
Authors: Lahti L. , Achim K. , Partanen J. 
Published: January 2013

AbstractThe midbrain GABAergic neurones control several aspects of behaviour, play important roles in psychiatric disease and are targets of medical treatments as well as drugs of abuse. However, their molecular diversity and regulation of development are only beginning to be understood. In this review, we briefly introduce distinct subpopulations of the midbrain GABAergic neurones and discuss knowledge on their development, including the developmental origins of midbrain GABAergic neurones as well as transcriptional regulatory mechanisms guiding their differentiation and identity. Important GABAergic neuron subpopulations are found within the dopaminergic (DA) nuclei in the ventral midbrain. GABAergic substantia nigra pars reticulata is the main output pathway of the basal ganglia system regulating voluntary movements. Recent studies have also highlighted importance of the GABAergic neurones associated with the ventral tegmental area for the control of DA neuron activity and motivated behaviours. Interestingly, the development of the GABAergic neurones associated with the DA nuclei is very different from the rest of the midbrain. Knowledge on developmental regulation can lead to insights into the molecular, structural and functional diversity of the midbrain GABAergic neurones and their subpopulations, cell groups of great physiological and medical interest.
Silencing of ASXL1 impairs the granulomonocytic lineage potential of human CD34+ progenitor cells
Authors: Davies Carwyn , Yip Bon Ham , Fernandez‐Mercado Marta , Woll Petter S. , Agirre Xabier , Prosper Felipe , Jacobsen Sten E. , Wainscoat James S. , Pellagatti Andrea , Boultwood Jacqueline 
Published: January 2013

SummaryThe ASXL1 gene encodes a chromatin‐binding protein involved in epigenetic regulation in haematopoietic cells. Loss‐of‐function ASXL1 mutations occur in patients with a range of myeloid malignancies and are associated with adverse outcome. We have used lentiviral‐based shRNA technology to investigate the effects of ASXL1 silencing on cell proliferation, apoptosis, myeloid differentiation and global gene expression in human CD34+ cells differentiated along the myeloid lineage in vitro. ASXL1‐deficient cells showed a significant decrease in the generation of CD11b+ and CD15+ cells, implicating impaired granulomonocytic differentiation. Furthermore, colony‐forming assays showed a significant increase in the number of multipotent mixed lineage colony‐forming unit (CFU‐GEMM) colonies and a significant decrease in the numbers of granulocyte‐macrophage CFU (CFU‐GM) and granulocyte CFU (CFU‐G) colonies in ASXL1‐deficient cells. Our data suggests that ASXL1 knockdown perturbs human granulomonocytic differentiation. Gene expression profiling identified many deregulated genes in the ASXL1‐deficient cells differentiated along the granulomonocytic lineage, and pathway analysis showed that the most significantly deregulated pathway was the LXR/RXR activation pathway. ASXL1 may play a key role in recruiting the polycomb repressor complex 2 (PRC2) to specific loci, and we found over‐representation of PRC2 targets among the deregulated genes in ASXL1‐deficient cells. These findings shed light on the functional role of ASXL1 in human myeloid differentiation.
Asymmetric Contribution of Isotopically Contrasting Food Sources to Vertebrate Consumers in a Subtropical Semi‐arid Ecosystem
Authors: Herrera Montalvo L. Gerardo , Rodríguez Galindo Malinalli , Ibarra López M. Pilar 
Published: January 2013

AbstractHabitat heterogeneity is a primary ecological factor that is particularly pronounced in arid ecosystems. The Tehuacán valley is a subtropical semi‐arid ecosystem in which several species of columnar cacti and agave (i.e., CAM plants) constitute the dominant elements accompanied by patches of trees and shrubs (i.e., C3 plants). Vegetation in Tehuacán is isotopically heterogenous because CAM plants have less depleted δ13C values than C3 plants. Fruits and flowers of cactus and agaves offer abundant food to vertebrates, but their leaves might be less attractive to insects than the leaves of C3 plants. Therefore, we use carbon and nitrogen stable isotope analysis to test the hypothesis that C3 and CAM food would contribute asymmetrically to different guilds of birds and bats. We predict that granivorous and frugivorous birds and nectarivorous and frugivorous bats will consume a CAM diet, whereas insectivorous birds and bats will consume a C3 diet. Due to omnivory of bird and bat consumers, we predict that the importance of CAM food will decrease as the trophic level of the animal increases. Our results showed that CAM food predominated in plant‐eating birds and in some flower‐visiting bats, whereas C3 food predominated in insect‐eating bats and birds and frugivorous bats. Habitat heterogeneity in Tehuacán is important for conservation due to the asymmetric role of CAM and C3 food in the nutrition of different feeding guilds of vertebrates. Our study provides basic information to evaluate the potential impact of habitat loss on functional groups of consumers in a semi‐arid ecosystem.
The Right Kind of Wrong: A “Knowledge in Pieces” Approach to Science Learning in Museums
Authors: Davis Pryce R. , Horn Michael S. , Sherin Bruce L. 
Published: January 2013

AbstractResearch has highlighted the vast gulf that exists between experts' and novices' understandings of science, and how difficult it is to bridge this gulf. When this research is applied to the design of museum exhibits and outreach material, it becomes clear that there is a tension between being scientifically correct and communicating effectively to a broad, diverse audience. In this paper we present a new approach to thinking about science learning in museums. Drawing on decades of research from the learning sciences, we argue that being “wrong” is an inescapable part of learning, and that not all simplifications are problematic. Instead, being “wrong” involves the gradual restructuring of many fine‐grained intuitive or commonsense notions that persist throughout the learning process and play an essential role in scientific expertise. We discuss the implications of adopting this approach for museum design.
The Great Immensity: A Theatrical Approach to Climate Change
Authors: Wasserman Sherri , Young Marion Friedman 
Published: January 2013

AbstractIn 2010, the Civilians—a New York based investigative theater company—received a three‐year grant from the National Science Foundation to develop The Great Immensity, a play addressing the complexity of climate change. The rigorous research that the Civilians puts into each production, the balance of scientific content and public engagement, the inclusion of scientists within the artistic development process, and the effort to engage a varied audience via a multi‐platform media approach, make the project a relevant case study for curators working with public science communication.
Mutualizing Museum Knowledge: Folksonomies and the Changing Shape of Expertise
Authors: Cairns Susan 
Published: January 2013

AbstractThe networking of knowledge in the Internet age is calling into question the relationship between experts and non‐experts in the development, preservation, and communication of knowledge. There is a growing movement towards knowledge co‐creation and “mutualization.” These changes in the roles of expertise will have implications for museums as traditional gatekeepers of knowledge. This paper will explore social tagging as one tactic for broaching the divide between experts and non‐experts in the online museum. Although tagging cannot mutualize museum knowledge itself, it can increase access to online collections, provide insight into users and their frameworks of perception, and begin to turn the online collection catalogue into a living historical document in its own right.
Prognostic impact of immune status and hematopoietic recovery before and after fludarabine, IV busulfan, and antithymocyte globulins (FB2 regimen) reduced‐intensity conditioning regimen (RIC) allogeneic stem cell transplantation (allo‐SCT)
Authors: Le Bourgeois Amandine , Lestang Elsa , Guillaume Thierry , Delaunay Jacques , Ayari Sameh , Blin Nicolas , Clavert Aline , Tessoulin Benoit , Dubruille Viviane , Mahe Beatrice , Roland Virginie , Gastinne Thomas , Le Gouill Steven , Moreau Philippe , Mohty Mohamad , Planche Lucie , Chevallier Patrice 
Published: January 2013

AbstractThis retrospective analysis aimed to assess hematopoietic and immune recovery in a cohort of 53 patients [males: n = 33; median age: 59 yr (range: 22–70)] who received a FB2 (fludarabine 120–150 mg/m² + IV busulfan 6.4 mg/kg + antithymocyte globulin thymoglobulin 5 mg/kg) reduced‐intensity conditioning (RIC) allo‐stem cells transplantations (SCT). With a median follow‐up of 19 months (range: 2–53), the 2‐yr overall survival, disease‐free survival (DFS), relapse incidence, and non‐relapse mortality were 63%, 59.5%, 35%, and 6%, respectively. In univariate analysis, the factors correlated with a significantly higher 2‐yr OS and DFS were a higher total circulating lymphocytes count at transplant (>730/mm3; OS: 81% vs. 43%, P = 0.02; DFS: 73% vs. 45.5%, P = 0.03) and a higher recovery of leukocytes (>5300/mm3) (2‐yr OS: 81% vs. 44%, P = 0.007; 2‐yr DFS: 72% vs. 46%, P = 0.08), neutrophils (>3200/mm3) (2‐yr OS: 76% vs. 50%, P = 0.03; 2‐yr DFS: 67% vs. 52.0%, P = 0.1), and monocytes (>590/mm3; 2‐yr OS: 80% vs. 45%, P = 0.004; 2‐yr DFS: 76% vs. 42%, P = 0.01) at day +30 post‐transplant. In multivariate analysis, the only independent factors associated with a significantly higher OS and DFS were a better immune status at transplant (lymphocytes count >730/mm3) and a higher monocytes count (>590/mm3) at day +30 post‐transplant. These results suggest that immune status and hematopoietic recovery before and after FB2 RIC allo‐SCT can be significant predictors of outcome. This paves the way for future studies aiming to closely monitor the kinetics of immune recovery after RIC allo‐SCT and to evaluate the impact of growth factors and other immunostimulatory cytokines in the setting of RIC allo‐SCT.
Weekly intravenous bortezomib is effective and well tolerated in relapsed/refractory myeloma
Authors: Moore Sally , Atwal Sangeeta , Sachchithanantham Sajitha , Streetly Matthew , Khan Iftekhar , Percy Laura , Narat Santosh , D'Sa Shirley , Rabin Neil , Johnston Rosalynd , Schey Steve , Yong Kwee 
Published: January 2013

AbstractObjectivesBortezomib is an effective antimyeloma therapy, but clinical benefits can be limited by neurotoxicity. In newly diagnosed, older patients, modification of the biweekly dosing schedule to weekly regimens improves tolerability whilst maintaining efficacy. There is less information on the efficacy and tolerability of weekly bortezomib regimens in the relapsed/refractory setting. Here, we report our experience of weekly intravenous bortezomib in clinical practice in relapsed/refractory patients.MethodsWe analysed fifty‐two patients who received weekly bortezomib for relapsed/refractory MM.ResultsThirty‐one per cent of patients received bortezomib beyond first relapse. Almost all (94%) also received steroids and 48% also received an alkylator. The median cumulative dose was 22.6 mg/m2, and median length of treatment was 164 d. Three patients reported grade 2 sensory neuropathy, and one reported grade 3 motor neuropathy. There were no grade 4 neurotoxicities. Eighty‐three per cent achieved a PR or greater, and the median PFS for the whole group was 13 months. One‐year PFS and OS were 53% (95% CI 39–66.6%) and 78% (95% CI 66.7–89.6%), respectively.ConclusionsWeekly intravenous bortezomib when used in combination with steroids ± alkylator is effective in relapsed/refractory MM, producing outcomes comparable with biweekly regimens and with lower rates of peripheral neuropathy.
Enduring increases in anxiety‐like behavior and rapid nucleus accumbens dopamine signaling in socially isolated rats
Authors: Yorgason Jordan T. , España Rodrigo A. , Konstantopoulos Joanne K. , Weiner Jeffrey L. , Jones Sara R. 
Published: January 2013

AbstractSocial isolation (SI) rearing, a model of early life stress, results in profound behavioral alterations, including increased anxiety‐like behavior, impaired sensorimotor gating and increased self‐administration of addictive substances. These changes are accompanied by alterations in mesolimbic dopamine function, such as increased dopamine and metabolite tissue content, increased dopamine responses to cues and psychostimulants, and increased dopamine neuron burst firing. Using voltammetric techniques, we examined the effects of SI rearing on dopamine transporter activity, vesicular release and dopamine D2‐type autoreceptor activity in the nucleus accumbens core. Long–Evans rats were housed in group (GH; 4/cage) or SI (1/cage) conditions from weaning into early adulthood [postnatal day (PD) 28–77]. After this initial housing period, rats were assessed on the elevated plus‐maze for an anxiety‐like phenotype, and then slice voltammetry experiments were performed. To study the enduring effects of SI rearing on anxiety‐like behavior and dopamine terminal function, another cohort of similarly reared rats was isolated for an additional 4 months (until PD 174) and then tested. Our findings demonstrate that SI rearing results in lasting increases in anxiety‐like behavior, dopamine release and dopamine transporter activity, but not D2 activity. Interestingly, GH‐reared rats that were isolated as adults did not develop the anxiety‐like behavior or dopamine changes seen in SI‐reared rats. Together, our data suggest that early life stress results in an anxiety‐like phenotype, with lasting increases in dopamine terminal function.
Motion parallax processing in pigeon (Columba livia) pretectal neurons
Authors: Xiao Qian , Frost Barrie J. 
Published: January 2013

AbstractIn the visual system of invertebrates and vertebrates there are specialised groups of motion‐sensitive neurons, with large receptive fields, which are optimally tuned to respond to optic flow produced by the animals' movement through the 3‐D world. From their response characteristics, shared frame of reference with the vestibular or inertial system, and anatomical connections, these neurons have been implicated in the stabilisation of retinal images, the control of posture and balance, and the animal's motion trajectories through the world. Using standard electrophysiological techniques and computer‐generated stimuli, we show that some of these flow‐field neurons in the pretectal nucleus lentiformis mesencephali in pigeons appear to be processing motion parallax. Two large overlapping planes of random dots moving independently were used to simulate motion parallax, in which one with larger dots was moved fast and the other with smaller dots was moved slowly in the opposite direction. Their neural responses to these two superimposed planes were facilitated above those produced by a single plane of moving dots and those produced by two layers moving in the same direction. Furthermore, some of these neurons preferred backward motion in the visual field and others preferred forward motion, suggesting that they may separately code visual objects ‘nearer’ and ‘farther’ than the stabilised (‘on’) plane during forward translational motion. A simple system is proposed whereby the relative activity in ‘near’, ‘far’ and ‘on’ populations could code depth through motion parallax in a metameric manner similar to that employed to code color vision and stereopsis.
Predictors of quality of life among multiple sclerosis patients: a comprehensive analysis
Authors: Yamout B. , Issa Z. , Herlopian A. , El Bejjani M. , Khalifa A. , Ghadieh A. S. , Habib R. H. 
Published: January 2013

Background and purposeMultiple sclerosis (MS) is a debilitating neurological disease of young people with substantial consequences on patients' quality of life (QOL). A variety of QOL instruments have been used to evaluate the efficacy of treatments. However, no study assessed the role of the different demographic, clinical, physical, social, economic and psychological parameters in the perception of patients with MS of their QOL.MethodsTwo‐hundred and one consecutive patients attending outpatient clinics were prospectively studied and objectively assessed using Expanded Disability Status Scale (EDSS), 8‐m walk test, and Symbol Digit Modality Test. Patients completed the following questionnaires: MS QOL‐54, Hamilton Depression Rating Scale, Fatigue Severity Scale, Brief Pain Inventory Average Pain Score, Drug Side‐Effects Severity Scale, Social Support, Religiosity, Physiotherapy and Exercise, and Socioeconomic Profile. Overall, QOL, physical (PHCS) and mental (MHCS) health composite scores were computed as outcome measures from MSQOL‐54.ResultsDepression, social support, religiosity, education years and living area predicted overall QOL by linear regression (R2 = 0.43). Unemployment and absence of fatigue correlated with poor and good QOL, respectively. Fatigue, pain, depression, EDSS, social support, MS type and anti‐cholinergic treatment predicted PHCS (R2 = 0.81). Fatigue, pain, depression, education years and social support predicted MHCS (R2 = 0.70).ConclusionThe QOL in patients with MS is not solely determined by physical disability, but rather by the level of social support, living area, depression, level of education, employment, fatigue and religiosity. Accordingly, we suggest that these should be evaluated in every patient with MS as they may be modified by targeted interventions.
Characterization of patients with recurrent ischaemic stroke using the ASCO classification
Authors: Wolf M. E. , Sauer T. , Hennerici M. G. , Chatzikonstantinou A. 
Published: January 2013

Background and purposeThe ASCO score has the advantage of allowing a more comprehensive characterization of ischaemic stroke patients and their risk factors, as reflected in different grades of evidence of atherosclerotic changes (A), small vessel disease (S), potential cardiac (C) or other (O) sources. It might also help to characterize patients with recurrent ischaemic stroke and document the etiology of stroke recurrence as well as the further development of risk factor constellations.MethodsWe prospectively screened our stroke database for patients with recurrent ischaemic stroke between 2004 and 2011, and classified each stroke using ASCO. The distribution of etiologies was analysed, and changes in the ASCO score were documented for each patient.ResultsWe identified 131 patients with recurrence of ischaemic stroke. At the first event, the distribution of etiologies and their grade of evidence was 97 grade 1 (A = 18/S = 32/C = 44/O = 3), six grade 2 (A = 2/S = 1/C = 3/O = 0), 199 grade 3 (A = 85/S = 83/C = 23/O = 8), 204 grade 0 (A = 26/S = 14/C = 44/O = 120) and 18 grade 9 (A = 0/S = 1/C = 17/O = 0). At stroke recurrence, 98 grade 1 (A = 16/S = 24/C = 55/O = 3), 11 grade 2 (A = 2/S = 5/C = 4/O = 0), 210 grade 3 (A = 94/S = 92/C = 13/O = 11), 171 grade 0 (A = 16/S = 9/C = 26/O = 117) and 34 grade 9 (A = 0/S = 1/C = 33/O = 0) were identified. Analysis of each individual showed a modification of the score in 85 patients (64.9%).ConclusionsRecurrent ischaemic stroke does not always have the same etiology as the previous one(s). Among variable changes of grade 1 etiologies, an increasing prevalence of cardioembolism – often insufficiently treated – at stroke recurrence was a major finding. ASCO proved to be highly useful to monitor risk factor constellations.
Vertebrobasilar dolichoectasia as a risk factor for cerebral microbleeds
Authors: Park J.‐M. , Koo J.‐S. , Kim B.‐K. , Kwon O. , Lee J. J. , Kang K. , Lee J. S. , Lee J. , Bae H.‐J. 
Published: January 2013

BackgroundBoth vertebrobasilar dolichoectasia (VBD) and cerebral microbleeds (CMBs) are related with the risk of intracerebral hemorrhage. We aimed to examine the relationship between the VBD and CMB in ischaemic stroke patients.MethodsA consecutive series of 182 patients hospitalized because of ischaemic stroke or transient ischaemic attack (TIA), and who underwent gradient echo brain magnetic resonance imaging were retrospectively recruited from a prospective stroke registry. CMB locations were categorized into anterior and posterior circulation. Ectasia was defined as basilar artery (BA) diameter > 4.5 mm, and dolichosis, as either BA bifurcation above the suprasellar cistern or lateral to the margin of the clivus or dorsum sellae. Whether VBD is associated with CMB anywhere in the brain or in anterior or posterior circulation territories was analysed using binary and multinomial logistic regression models.ResultsTwenty‐four subjects (13.2%) had VBD and 48 (26.4%) had CMBs. CMBs were more frequently observed in patients with VBD than without (66.7% vs. 20.3%, P < 0.001). VBD was significantly associated with CMBs in any location (crude odds ratio, 7.88; 95% confidence interval, 3.10–20.02), in the posterior circulation territory only (9.63; 2.60–34.94), and in both territories (9.25; 3.40–26.29), but not in the anterior circulation only (1.14; 0.009–11.20). These associations remained unchanged after adjusting for age, gender, hypertension, leukoaraiosis and stroke subtype.ConclusionsVBD in patients with ischaemic stroke or TIA is independently associated with CMBs, especially in the posterior circulation territory.