bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gabapentin Enacarbil Extended‐Release for Alcohol Use Disorder: A Randomized, Double‐Blind, Placebo‐Controlled, Multisite Trial Assessing Efficacy and Safety
Authors: Falk Daniel E. , Ryan Megan L. , Fertig Joanne B. , Devine Eric G. , Cruz Ricardo , Brown E. Sherwood , Burns Heather , Salloum Ihsan M. , Newport D. Jeffrey , Mendelson John , Galloway Gantt , Kampman Kyle , Brooks Catherine , Green Alan I. , Brunette Mary F. , Rosenthal Richard N. , Dunn Kelly E. , Strain Eric C. , Ray Lara , Shoptaw Steven , Ait‐Daoud Tiouririne Nassima , Gunderson Erik W. , Ransom Janet , Scott Charles , Leggio Lorenzo , Caras Steven , Mason Barbara J. , Litten Raye Z. ,   the National Institute on Alcohol Abuse and Alcoholism Clinical Investigations Group (NCIG) Study Group
Published: November 2018

BackgroundSeveral single‐site alcohol treatment clinical trials have demonstrated efficacy for immediate‐release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended‐release (GE‐XR) (HORIZANT®), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD).MethodsMen and women (n = 346) who met DSM‐5 criteria for at least moderate AUD were recruited across 10 U.S. clinical sites. Participants received double‐blind GE‐XR (600 mg twice a day) or placebo and a computerized behavioral intervention (Take Control) for 6 months. Efficacy analyses were prespecified for the last 4 weeks of the treatment period.ResultsThe GE‐XR and placebo groups did not differ significantly on the primary outcome measure, percentage of subjects with no heavy drinking days (28.3 vs. 21.5, respectively, p = 0.157). Similarly, no clinical benefit was found for other drinking measures (percent subjects abstinent, percent days abstinent, percent heavy drinking days, drinks per week, drinks per drinking day), alcohol craving, alcohol‐related consequences, sleep problems, smoking, and depression/anxiety symptoms. Common side‐effects were fatigue, dizziness, and somnolence. A population pharmacokinetics analysis revealed that patients had lower gabapentin exposure levels compared with those in other studies using a similar dose but for other indications.ConclusionsOverall, GE‐XR at 600 mg twice a day did not reduce alcohol consumption or craving in individuals with AUD. It is possible that, unlike the IR formulation of gabapentin, which showed efficacy in smaller Phase 2 trials at a higher dose, GE‐XR is not effective in treating AUD, at least not at doses approved by the U.S. Food and Drug Administration for treating other medical conditions.
4‐Phenylbutyric Acid Protects Against Ethanol‐Induced Damage in the Developing Mouse Brain
Authors: Li Hui , Wen Wen , Xu Hong , Wu Huaxun , Xu Mei , Frank Jacqueline A. , Luo Jia 
Published: November 2018

BackgroundEthanol (EtOH) exposure during pregnancy may result in fetal alcohol spectrum disorders (FASD). One of the most deleterious consequences of EtOH exposure is neuronal loss in the developing brain. Previously, we showed that EtOH exposure induced neuroapoptosis in the brain of postnatal day 4 (PD4) mice but not PD12 mice. This differential susceptibility may result from an insufficient cellular stress response system such as unfolded protein response (also known as endoplasmic reticulum [ER] stress) in PD4 mice. In this study, we compared the effect of EtOH on ER stress in PD4 and PD12 mice and determined whether the inhibition of ER stress could protect the developing brain against EtOH damage.MethodsWe used a third‐trimester equivalent mouse model of FASD. PD4 and PD12 C57BL/6 mice were subcutaneously injected with saline (control), EtOH, EtOH plus 4‐phenylbutyric acid (4‐PBA), a chemical chaperone known as ER stress inhibitor, and 4‐PBA alone. The expression of apoptosis marker, ER stress markers, and markers for glial cell activation was examined in the cerebral cortex.ResultsEtOH induced neuroapoptosis and increased the expression of ER stress markers, such as activating transcription factor 6, 78‐kDa glucose‐regulated protein, inositol‐requiring enzyme 1α, mesencephalic astrocyte‐derived neurotrophic factor, and caspase‐12 in PD4 but not PD12 mice. EtOH exposure also activated microglia and astrocytes. Interestingly, treatment with 4‐PBA attenuated EtOH‐induced neuroapoptosis. Moreover, 4‐PBA inhibited the expression of the aforementioned ER stress markers and EtOH‐induced glial activation in PD4 mice.ConclusionsER stress plays an important role in EtOH‐induced damage to the developing brain. Inhibition of ER stress is neuroprotective and may provide a new therapeutic strategy for treating FASD.
Histopathological findings of an exposed human pulp carbonised by CO2 laser irradiation: A case report
Authors: Suzuki Masaya , Kato Chikage , Kawashima Satoki , Shinkai Koichi 
Published: November 2018

AbstractThis report shows the healing process of an exposed pulp carbonised by CO2 laser irradiation prior to the application of a capping material. Six intact teeth from four volunteers were irradiated by CO2 laser and randomly capped with either an adhesive resin (SE bond) (n = 3) or calcium hydroxide‐based cement (Dycal) (n = 3). The laser was operated in super‐pulsed mode (power output, 0.5 W) for an irradiation time of 30 s. All cavities were restored with composite resin. Each tooth was extracted at approximately 30, 50 or 260 days post treatment and prepared for histological evaluation. CO2 laser irradiation controlled exudate and bleeding from each exposed pulp. Histological images revealed Dycal promoted complete dentine bridge formation at the carbonised pulp surface, and laser energy affected not only the pulp surface but also the deeper part of the pulp chamber.
Active vaccination against interleukin‐5 as long‐term treatment for insect‐bite hypersensitivity in horses
Authors: Fettelschoss‐Gabriel Antonia , Fettelschoss Victoria , Olomski Florian , Birkmann Katharina , Thoms Franziska , Bühler Maya , Kummer Martin , Zeltins Andris , Kündig Thomas M. , Bachmann Martin F. 
Published: November 2018

AbstractBackgroundInsect‐bite hypersensitivity (IBH) in horses is a chronic allergic dermatitis caused by insect bites. Horses suffer from pruritic skin lesions, caused by type‐I/type‐IV allergic reactions accompanied by prominent eosinophil infiltration into the skin. Interleukin‐5 (IL‐5) is the key cytokine for eosinophils and we have previously shown that targeting IL‐5 by vaccination reduces disease symptoms in horses.ObjectiveHere, we analyzed the potential for long‐term therapy by assessing a second follow‐up year of the previously published study.MethodsThe vaccine consisted of equine IL‐5 (eIL‐5) covalently linked to a cucumber mosaic virus‐like particle (VLP) containing a universal T cell epitope (CuMVTT) using a semi‐crossover design to follow vaccinated horses during a second treatment season. Thirty Icelandic horses were immunized with 300 μg of eIL‐5‐CuMVTT without adjuvant.ResultsThe vaccine was well tolerated and did not reveal any safety concerns throughout the study. Upon vaccination, all horses developed reversible anti‐eIL‐5 auto‐antibody titers. The mean course of eosinophil levels was reduced compared to placebo treatment leading to significant reduction of clinical lesion scores. Horses in their second vaccination year showed a more pronounced improvement of disease symptoms when compared to first treatment year, most likely due to more stable antibody titers induced by a single booster injection. Hence, responses could be maintained over two seasons and the horses remained protected against disease symptoms.ConclusionYearly vaccination against IL‐5 may be a long‐term solution for the treatment of IBH and other eosinophil‐mediated diseases in horses and other species including humans.
Chitinase 3‐like 1 protein plays a critical role in respiratory syncytial virus‐induced airway inflammation
Authors: Kim Min Jung , Shim Doo Hee , Cha Hye‐Ran , Moon Kuk‐Young , Yang Chang Mo , Hwang Su Jin , Kim Kyung Won , Park Jeon Han , Lee Chun Geun , Elias Jack A. , Sohn Myung Hyun , Lee Jae Myun 
Published: November 2018

AbstractBackgroundChitinase 3‐like 1 protein (CHI3L1) (YKL‐40 in humans and breast regression protein [BRP]‐39 in mice) is required for optimal allergen sensitization and Th2 inflammation in various chronic inflammatory diseases including asthma. However, the role of CHI3L1 in airway inflammation induced by respiratory viruses has not been investigated. The aim of this study was to investigate the relationship between CHI3L1 and airway inflammation caused by respiratory syncytial virus (RSV) infection.MethodsWe measured YKL‐40 levels in human nasopharyngeal aspirate (NPA) from hospitalized children presenting with acute respiratory symptoms. Wild‐type (WT) and BRP‐39 knockout (KO) C57BL/6 mice were inoculated with live RSV (A2 strain). Bronchoalveolar lavage fluid and lung tissue samples were obtained on day 7 after inoculation to assess lung inflammation, airway reactivity, and expression of cytokines and BRP‐39.ResultsIn human subjects, YKL‐40 and IL‐13 levels in NPA were higher in children with RSV infection than in control subjects. Expression of BRP‐39 and Th2 cytokines, IL‐13 in particular, was increased following RSV infection in mice. Airway inflammation caused by RSV infection was reduced in BRP‐39 KO mice as compared to WT mice. Th2 cytokine levels were not increased in the lungs of RSV‐infected BRP‐39 KO mice. BRP‐39 regulated M2 macrophage activation in RSV‐infected mice. Additionally, treatment with anti‐CHI3L1 antibody attenuated airway inflammation and Th2 cytokine production in RSV‐infected WT mice.ConclusionThese findings suggest that CHI3L1 could contribute to airway inflammation induced by RSV infection. CHI3L1 could be a potential therapeutic candidate for attenuating Th2‐associated immunopathology during RSV infection.
Electrocardiographic predictors of myocardial fibrosis and apical hypertrophic cardiomyopathy
Authors: Tangwiwat Chayapat , Kaolawanich Yodying , Krittayaphong Rungroj 
Published: November 2018

AbstractBackgroundElectrocardiography (ECG) may be an efficacious diagnostic and prognostic tool in hypertrophic cardiomyopathy (HCM). This study aimed to investigate association between deep T‐wave inversion (TWI) and apical HCM, and between fragmented QRS (fQRS) complex and myocardial fibrosis in patients with HCM.MethodsPatients with documented HCM by cardiac magnetic resonance imaging (CMR) during 2005–2015 were studied. The 12‐lead ECG and CMR were performed on the same day. All patients underwent CMR for the assessment of cardiac structure, function, and late gadolinium enhancement (LGE). LGE was used to detect myocardial fibrosis.ResultsOne hundred forty‐four HCM (mean age 66 ± 15.8 years, 60.4% male) were included. Twenty‐nine (20.14%) subjects had deep TWI, and apical HCM was found in 76 (52.78%). Deep TWI was associated with apical HCM with the Odds ratio (95%CI) of 5.82 (2.07, 16.04) and p < 0.001 in univariate analysis model. The association was still significant in multivariate analysis with adjusted Odds ratio (95%CI) of 9.86 (3.17, 30.66), p < 0.001. Forty‐seven (32.64%) subjects had fQRS complex, and myocardial fibrosis was detected in 101 (70.14%). fQRS complex was found to be associated with myocardial fibrosis in univariate analysis with the Odds ratio (95%CI) = 2.75 (1.16, 6.54), p = 0.019. However, the association cannot be demonstrated in the multivariate analysis.ConclusionDeep TWI is independently associated with apical HCM, but the relationship between fQRS complex and myocardial fibrosis did not survive multivariate analysis.
The Limits of Liberal Recognition: Racial Capitalism, Settler Colonialism, and Environmental Governance in Vancouver and Atlanta
Authors: McCreary Tyler , Milligan Richard 
Published: November 2018

AbstractDespite increasing institutionalised recognition of Indigenous and Black environmental concerns in governance processes, the structures of settler colonialism and racial capitalism in North America continue to normalise dispossession and disproportionately burden marginalised communities with environmental harms. Engaging recent critiques of the inability of Indigenous rights frameworks to reverse ongoing colonial dispossessions and the failure of environmental justice policies to address racialised environmental inequalities, this article argues that political ecologists must contend with the limitations of institutionalisedrecognitionof historically marginalised communities in North American environmental governance. We argue that institutionalisation of such concern, while putatively redressing injustices or reconciling dispossession through environmental governance, functions more to elide historic drivers and geographic processes of marginalisation than to disrupt white supremacy and settler colonialism.
The Pluralities of Black Geographies
Authors: Bledsoe Adam , Wright Willie Jamaal 
Published: November 2018

AbstractThis paper seeks to spur conversations around the inherent pluralities found within Black Geographies. While analyses of Black Geographies have provided important reflections on the spatial imaginaries and practices of Black populations, less attention has been paid to the differences found among Black geographical expressions. This piece therefore seeks to draw out the ways in which Black people uniquely conceive of space by highlighting the distinctions present within different Black social movements. The authors explore the spatial politics of the Universal Negro Improvement Association, the Black Panther Party for Self‐Defense, and the Provisional Government of the Republic of New Afrika to argue that while these three movements all attempted to create spaces of Black self‐determination, they did so with distinct spatial aspirations and concrete politics. The authors argue that recognising and accounting for the pluralities of Black spatial creation is necessary for realising more just geographies.
Ultrastructure of the spermatozoa of three species of Anomalodesmata (Mollusca, Bivalvia) and phylogenetic implications
Authors: Campos Ariane , Introíni Gisele Orlandi , Tallarico Lenita de Freitas , Passos Flávio Dias , Machado Fabrizio Marcondes , Recco‐Pimentel Shirlei Maria 
Published: November 2018

AbstractAnomalodesmata is the rarest and most specialized group of the class Bivalvia. In general, scarce data on sperm ultrastructure of anomalodesmatans are available in the literature. Aiming to contribute to an understanding of spermatozoon morphology in this group, the present study describes the ultrastructure of male gametes of three species—Cardiomya cleryana (Orbigny 1842) (Cuspidariidae), Pandora brevirostris Güller and Zelaya 2016 (Pandoridae) and Thracia similis Couthouy 1839 (Thraciidae). C. cleryana has an acrosome located at the anterior region, and the mitochondria are symmetrically arranged, while the spermatozoa of P. brevirostris and T. similis have unique characteristics, in particular the association of the acrosome with the midpiece and asymmetric mitochondria. This position of the acrosome appears to be peculiar among Anomalodesmata and is unknown for non‐anomalodesmatan bivalves. The present ultrastructural description of spermatozoa contributes to differentiate the studied species, bringing new insights about the sperm features of anomalodesmatan species and shares several characteristics with that of other species of the two lineages proposed by molecular phylogeny.
Regulation of glioma cell invasion by 3q26 gene products PIK3CA, SOX2 and OPA1
Authors: Schaefer Thorsten , Ramadoss Archana , Leu Severina , Tintignac Lionel , Tostado Cristobal , Bink Andrea , Schürch Christoph , Müller Joëlle , Schärer Jonas , Moffa Giusi , Demougin Philippe , Moes Suzette , Stippich Christoph , Falbo Simona , Neddersen Heike , Bucher Heiner , Frank Stephan , Jenö Paul , Lengerke Claudia , Ritz Marie‐Françoise , Mariani Luigi , Boulay Jean‐Louis 
Published: November 2018

AbstractDiffuse gliomas progress by invading neighboring brain tissue to promote postoperative relapse. Transcription factor SOX2 is highly expressed in invasive gliomas and maps to chromosome region 3q26 together with the genes for PI3K/AKT signaling activator PIK3CA and effector molecules of mitochondria fusion and cell invasion, MFN1 and OPA1. Gene copy number analysis at 3q26 from 129 glioma patient biopsies revealed mutually exclusive SOX2 amplifications (26%) and OPA1 losses (19%). Both forced SOX2 expression and OPA1 inactivation increased LN319 glioma cell invasion in vitro and promoted cell dispersion in vivo in xenotransplanted D. rerio embryos. While PI3 kinase activity sustained SOX2 expression, pharmacological PI3K/AKT pathway inhibition decreased invasion and resulted in SOX2 nucleus‐to‐cytoplasm translocation in an mTORC1‐independent manner. Chromatin immunoprecipitation and luciferase reporter gene assays together demonstrated that SOX2 trans‐activates PIK3CA and OPA1. Thus, SOX2 activates PI3K/AKT signaling in a positive feedback loop, while OPA1 deletion is interpreted to counteract OPA1 trans‐activation. Remarkably, neuroimaging of human gliomas with high SOX2 or low OPA1 genomic imbalances revealed significantly larger necrotic tumor zone volumes, corresponding to higher invasive capacities of tumors, while autologous necrotic cells are capable of inducing higher invasion in SOX2 overexpressing or OPA1 knocked‐down relative to parental LN319. We thus propose necrosis volume as a surrogate marker for the assessment of glioma invasive potential. Whereas glioma invasion is activated by a PI3K/AKT‐SOX2 loop, it is reduced by a cryptic invasion suppressor SOX2‐OPA1 pathway. Thus, PI3K/AKT‐SOX2 and mitochondria fission represent connected signaling networks regulating glioma invasion.
Natural compounds with xanthine oxidase inhibitory activity: A review
Authors: Mehmood Arshad , Ishaq Muhammad , Zhao Lei , Safdar Bushra , Rehman Ashfaq‐ur , Munir Masooma , Raza Ali , Nadeem Muhammad , Iqbal Waheed , Wang Chengtao 
Published: November 2018

AbstractHyperuricemia (HUA), a disease due to an elevation of body uric acid level and responsible for various diseases such as gout, cardiovascular disorders, and renal failure, is a major ground debate for the medical science these days. Considering the risk factors linked with allopathic drugs for the treatment of this disease, the debate has now become a special issue. Previously, we critically discussed the role of dietary polyphenols in the treatment of HUA. Besides dietary food plants, many researchers figure out the tremendous effects of medicinal plants‐derived phytochemicals against HUA. Keeping in mind all these aspects, we reviewed all possible managerial studies related to HUA through medicinal plants (isolated compounds). In the current review article, we comprehensively discussed various bioactive compounds, chemical structures, and structure–activity relationship with responsible key enzyme xanthine oxidase.
Amyloid beta soluble forms and plasminogen activation system in Alzheimer’s disease: Consequences on extracellular maturation of brain‐derived neurotrophic factor and therapeutic implications
Authors: Angelucci Francesco , Čechová Kateřina , Průša Richard , Hort Jakub 
Published: November 2018

SummarySoluble oligomeric forms of amyloid beta (Aβ) play an important role in causing the cognitive deficits in Alzheimer’s disease (AD) by targeting and disrupting synaptic pathways. Thus, the present research is directed toward identifying the neuronal pathways targeted by soluble forms and, accordingly, develops alternative therapeutic strategies. The neurotrophin brain‐derived neurotrophic factor (BDNF) is synthesized as a precursor (pro‐BDNF) which is cleaved extracellularly by plasmin to release the mature form. The conversion from pro‐BDNF to BDNF is an important process that regulates neuronal activity and memory processes. Plasmin‐dependent maturation of BDNF in the brain is regulated by plasminogen activator inhibitor‐1 (PAI‐1), the natural inhibitor of tissue‐type plasminogen activator (tPA). Therefore, tPA/PAI‐1 system represents an important regulator of extracellular BDNF/pro‐BDNF ratio. In this review, we summarize the data on the components of the plasminogen activation system and on BDNF in AD. Moreover, we will hypothesize a possible pathogenic mechanism caused by soluble Aβ forms based on the effects on tPA/PAI‐1 system and on the consequence of an altered conversion from pro‐BDNF to the mature BDNF in the brain of AD patients. Translation into clinic may include a better characterization of the disease stage and future direction on therapeutic targets.
Efficacy of cannabinoids in paediatric epilepsy
Authors: Ali Shayma , Scheffer Ingrid E , Sadleir Lynette G 
Published: November 2018

There are hundreds of compounds found in the marijuana plant, each contributing differently to the antiepileptic and psychiatric effects. Cannabidiol (CBD) has the most evidence of antiepileptic efficacy and does not have the psychoactive effects of ∆9‐tetrahydrocannabinol. CBD does not act via cannabinoid receptors and its antiepileptic mechanism of action is unknown. Despite considerable community interest in the use of CBD for paediatric epilepsy, there has been little evidence for its use apart from anecdotal reports, until the last year. Three randomized, placebo‐controlled, double‐blind trials in Dravet syndrome and Lennox–Gastaut syndrome found that CBD produced a 38% to 41% median reduction in all seizures compared to 13% to 19% on placebo. Similarly, CBD resulted in a 39% to 46% responder rate (50% convulsive or drop‐seizure reduction) compared to 14% to 27% on placebo. CBD was well tolerated; however, sedation, diarrhoea, and decreased appetite were frequent. CBD shows similar efficacy to established antiepileptic drugs.What this paper adds

Cannabidiol (CBD) shows similar efficacy in the severe paediatric epilepsies to other antiepileptic drugs.

Careful down‐titration of benzodiazepines is essential to minimize sedation with adjunctive CBD.