bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein kinase inhibitors in the treatment of inflammatory and autoimmune diseases
Authors: Patterson H , Nibbs R , McInnes I , Siebert S 
Published: December 2013

SummaryProtein kinases mediate protein phosphorylation, which is a fundamental component of cell signalling, with crucial roles in most signal transduction cascades: from controlling cell growth and proliferation to the initiation and regulation of immunological responses. Aberrant kinase activity is implicated in an increasing number of diseases, with more than 400 human diseases now linked either directly or indirectly to protein kinases. Protein kinases are therefore regarded as highly important drug targets, and are the subject of intensive research activity. The success of small molecule kinase inhibitors in the treatment of cancer, coupled with a greater understanding of inflammatory signalling cascades, has led to kinase inhibitors taking centre stage in the pursuit for new anti-inflammatory agents for the treatment of immune-mediated diseases. Herein we discuss the main classes of kinase inhibitors; namely Janus kinase (JAK), mitogen-activated protein kinase (MAPK) and spleen tyrosine kinase (Syk) inhibitors. We provide a mechanistic insight into how these inhibitors interfere with kinase signalling pathways and discuss the clinical successes and failures in the implementation of kinase-directed therapeutics in the context of inflammatory and autoimmune disorders.
A digital evaluation of alveolar ridge preservation at implants placed immediately into extraction sockets: an experimental study in the dog
Authors: Favero Giacomo , Lang Niklaus P. , Romanelli Piero , Pantani Fabio , Caneva Marco , Botticelli Daniele 
Published: December 2013

AbstractObjectiveTo compare with pristine sites bone resorption and soft tissue adaptation at implants placed immediately into extraction sockets (IPIES) in conjunction with deproteinized bovine bone mineral (DBBM) particles and a collagen membrane.Material and methodsThe mesial root of the third premolar in the left side of the mandible was endodontically treated (Test). Flaps were elevated, the tooth hemi‐sectioned, and the distal root removed to allow the immediate installation of an implant into the extraction socket in a lingual position. DBBM particles were placed into the defect and on the outer contour of the buccal bony ridge, concomitantly with the placement of a collagen membrane. A non‐submerged healing was allowed. The premolar on the right side of the mandible was left in situ (control). Ground sections from the center of the implant as well as from the center of the distal root of the third premolar of the opposite side of the mandible were obtained. The histological image from the implant site was superimposed to that of the contralateral pristine distal alveolus, and dimensional variation evaluated for the hard tissue and the alveolar ridge.ResultsAfter 3 months of healing, both histological and photographic evaluation revealed a reduction of hard and soft tissue dimensions.ConclusionThe contour augmentation performed with DBBM particles and a collagen membrane at the buccal aspects of implants placed IPIES was not able to maintain the tissue volume.
Dysfunctional and compensatory synaptic plasticity in Parkinson's disease
Authors: Schroll Henning , Vitay Julien , Hamker Fred H. 
Published: December 2013

AbstractIn Parkinson's disease, a loss of dopamine neurons causes severe motor impairments. These motor impairments have long been thought to result exclusively from immediate effects of dopamine loss on neuronal firing in basal ganglia, causing imbalances of basal ganglia pathways. However, motor impairments and pathway imbalances may also result from dysfunctional synaptic plasticity – a novel concept of how Parkinsonian symptoms evolve. Here we built a neuro‐computational model that allows us to simulate the effects of dopamine loss on synaptic plasticity in basal ganglia. Our simulations confirm that dysfunctional synaptic plasticity can indeed explain the emergence of both motor impairments and pathway imbalances in Parkinson's disease, thus corroborating the novel concept. By predicting that dysfunctional plasticity results not only in reduced activation of desired responses, but also in their active inhibition, our simulations provide novel testable predictions. When simulating dopamine replacement therapy (which is a standard treatment in clinical practice), we observe a new balance of pathway outputs, rather than a simple restoration of non‐Parkinsonian states. In addition, high doses of replacement are shown to result in overshooting motor activity, in line with empirical evidence. Finally, our simulations provide an explanation for the intensely debated paradox that focused basal ganglia lesions alleviate Parkinsonian symptoms, but do not impair performance in healthy animals. Overall, our simulations suggest that the effects of dopamine loss on synaptic plasticity play an essential role in the development of Parkinsonian symptoms, thus arguing for a re‐conceptualisation of Parkinsonian pathophysiology.
Overview of presurgical assessment and surgical treatment of epilepsy from the Italian League Against Epilepsy
Authors: Guerrini Renzo , Scerrati Massimo , Rubboli Guido , Esposito Vincenzo , Colicchio Gabriella , Cossu Massimo , Marras Carlo Efisio , Tassi Laura , Tinuper Paolo , Paola Canevini Maria , Quarato Pierpaolo , Giordano Flavio , Granata Tiziana , Villani Flavio , Giulioni Marco , Scarpa Pina , Barbieri Valentina , Bottini Gabriella , Del Sole Angelo , Vatti Giampaolo , Spreafico Roberto , Lo Russo Giorgio ,   the Commission for Epilepsy Surgery of the Italian League Against Epilepsy
Published: December 2013

SummaryThe Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) presents an overview of the techniques and methodologies of presurgical evaluation and of the surgical treatment of epilepsies. This overview is the result of the experience developed in the past years in the major Italian centers where programs of epilepsy surgery have been established, and it has the aim of offering a quick and easy reference tool for those involved in the treatment of patients with epilepsy. The sharing of different experiences has the additional aim of conforming and disseminating the employed techniques as well as the methods of selection and evaluation of patients. The synthetic coverage of the main issues concerning the presurgical workup and the available surgical options will hopefully provide a framework that may integrate and develop the contributions of every single center, in one of the more complex, challenging, and dynamic areas of neurological sciences.
Health Technology Assessment report on the presurgical evaluation and surgical treatment of drug‐resistant epilepsy
Authors: Marras Carlo Efisio , Canevini Maria Paola , Colicchio Gabriella , Guerrini Renzo , Rubboli Guido , Scerrati Massimo , Spreafico Roberto , Tassi Laura , LoRusso Giorgio , Tinuper Paolo ,   the Commission on Epilepsy Surgery of the Italian League Against Epilepsy
Published: December 2013

SummaryPurposeEpilepsy is a neurologic disorder with major social impact. Surgery is a valuable option in patients who are not responding to antiepileptic drugs. The literature reports demonstrate that a proportion ranging from 40 to 100% of patients with epilepsy achieve seizure remission after surgery. A presurgical evaluation (clinical and instrumental) must be performed in all patients with drug‐resistant epilepsy to assess their suitability for surgical intervention.HealthTechnologyAssessment (HTA) represents a modern approach to the analysis of technologies used for health care.HTAcould be considered a bridge between science that produces evidence and the decisions that can be taken on the basis of that evidence at different levels of the health care system. The aim of this study is theHTAof epilepsy surgery including clinical, ethical, social, and economic features.MethodsThe present study includes an analysis of the diagnostic and surgical workup performed at theItaliancenters for the diagnosis and treatment of drug‐resistant epilepsy (DRE). The study includes the following issues: (1) social, ethical impact, and costs of the disease; (2) clinical results, efficacy, and safety of surgery; (3) ethics and quality of life after surgery; and (4) economic impact and productivity regained after surgery. The cost of managing a patient with DRE included in the presurgical study was estimated by the bottom‐up microcosting technique that starts from a detailed collection of data on consumption of resources and full costing. The phases analyzed were (1) noninvasive diagnostic workup; (2) neurosurgical intervention; and (3) follow‐up.Key FindingsThe literature reports indicate epilepsy surgery as an effective treatment both on clinical results and on ethical, social, and quality of life aspects. The workup including the noninvasive presurgical study followed by surgery has a total cost of €20,827. Management of short‐term follow‐up increases the overhead to €22,291 at the first year, and then to €23,571 after 5 years. According to the estimates made in this survey, funding based on diagnosis‐related group (DRG) tariff for the noninvasive diagnostic stage involving hospital admission is not remunerative in Italy either at regional or national levels. Effectively the difference between full cost andDRGhas a delta of €3,402 and €2,537 respectively. The total cost of the presurgical, surgical, and follow‐up evaluation is not remunerative for €10,554 (national data).SignificanceEconomic surveys in Italy have shown that surgery for DRE is an advantageous treatment from the standpoint of third‐party payers and is cost‐effective for society.DREpresurgical evaluation and surgery are not remunerative either at regional or national levels.
The spectrum of epileptic syndromes with fixation off sensitivity persisting in adult life
Authors: Fattouch Jinane , Casciato Sara , Lapenta Leonardo , Morano Alessandra , Fanella Martina , Lombardi Laura , Manfredi Mario , Giallonardo Anna Teresa , Di Bonaventura Carlo 
Published: December 2013

SummaryPurposeThe term “fixation off sensitivity” (FOS) was proposed by Panayiotopoulos to describe epilepsy/electroencephalography (EEG) changes evoked by the suppression of central vision and fixation. The EEG pattern usually consists of spike/polyspike and waves localized in occipital regions. FOS occurs mainly in children with idiopathic occipital partial epilepsies and rarely in adults. In this retrospective study we evaluated the clinical data, EEG, and magnetic resonance imaging (MRI) findings of patients with epilepsy and FOS persisting in adult life to better define the spectrum of syndromes.MethodsWe selected 15 consecutive patients (12 female/3 male; age range 19–59 years). The main inclusion criterion was the diagnosis of epilepsy with FOS persisting in adult life. We retrospectively analyzed clinical EEG and neuroimaging data.Key FindingsWe observed a female prevalence (F/M = 12/3). Eight patients presented both simple and complex partial seizures, whereas seven had only complex partial seizures. Partial seizures evolved into generalized seizures/hemiconvulsions in nine cases. The FOS pattern consisted of spike‐and‐wave and slow‐wave abnormalities with posterior localization (bilateral in eight/monolateral in seven). We recorded seizures in 10/15 patients. All showed a posterior onset (bilateral in 2/left in 2/right in 6). FOS was prevalent in symptomatic epilepsy (cortical malformations in 7; celiac disease in 3; calcified vascular malformation in 1). One patient presented cryptogenic epilepsy and only three idiopathic epilepsy (Gastaut syndrome).SignificanceFOS can be observed in adult life in idiopathic epilepsy, representing the “prolongation” of the same phenomenon arisen during childhood. Nevertheless, it often represents the EEG expression of symptomatic epilepsies (cortical malformations/celiac disease).
Epilepsy in primary cerebral tumors: The characteristics of epilepsy at the onset (results from the PERNO study – Project of Emilia Romagna Region on Neuro‐Oncology)
Authors: Michelucci Roberto , Pasini Elena , Meletti Stefano , Fallica Elisa , Rizzi Romana , Florindo Irene , Chiari Annalisa , Monetti Cinzia , Cremonini Anna Maria , Forlivesi Stefano , Albani Fiorenzo , Baruzzi Agostino ,   the PERNO Study Group
Published: December 2013

SummaryPurposeTo present new information on the semiology and short‐term evolution of seizures associated with primary brain tumors (PBTs) in a prospective study.MethodsThis study is a section of the PERNO study – Project of Emilia Romagna Region on Neuro‐Oncology, the main aim of which is to collect prospectively all cases of PBTs occurring in the Emilia‐Romagna region, northeast Italy (3,983,346 population) from January 2009 to December 2011, to allow epidemiologic, clinical, and biomolecular studies.The epilepsy section of the PERNO study included all the patients who experienced seizures, either as first symptom of the tumor or appearing during the course of the disease. Each patient was interviewed by the referring neurologist with a specific interest in epilepsy. The patients who entered the study were followed up with visits on a quarterly basis.Key FindingsWe collected 100 cases with full clinical, neuroradiologic, and pathologic data. The majority (79%) had high grade PBTs (glioblastoma in 50 cases), whereas the remaining patients had low‐grade gliomas, mostly localized in the frontal (60%), temporal (38%), and parietal (28%) lobes. Seizures were the first symptom of the tumor in 72 cases. Overall, the initial seizures were tonic–clonic (48%) (without clear initial focal signs in more than half of the patients), focal motor (26%), complex partial (10%), and somatosensitive (8%). The majority of cases (60%) had isolated seizures or a low seizure frequency at the onset of the disease, whereas a high seizure frequency or status epilepticus was observed in 18% and 12% of cases, respectively. Ninety‐two patients underwent surgical removal of the tumor, which was either radical (38%) or partial (53%). Seven patients underwent only cerebral biopsy. In the 72 patients in whom seizures were the first symptom, the mean time to the surgical treatment was 174 days, with a significant difference between high grade (95 days) and low grade (481 days) gliomas.At the time of our first observation, the majority of patients (69%) had already undergone surgical removal, with a mean follow‐up of 3 months after the procedure. Overall, 39 patients (56%) were seizure free after tumor removal. The good outcome did not depend on presurgical seizure frequency or tumor type, although there was a trend for better results with low‐grade PBTs.SignificanceThese data provide evidence that seizures are strictly linked to the tumoral lesion: They are the initial symptom of the tumor, reflect the tumor location and type, are usually resistant to antiepileptic treatment, and may disappear after the treatment of the lesion.
Different responses of soil respiration and its components to nitrogen addition among biomes: a meta‐analysis
Authors: Zhou Lingyan , Zhou Xuhui , Zhang Baocheng , Lu Meng , Luo Yiqi , Liu Lingli , Li Bo 
Published: December 2013

AbstractAnthropogenic activities have increased nitrogen (N) deposition by threefold to fivefold over the last century, which may considerably affect soil respiration (Rs). Although numerous individual studies and a few meta‐analyses have been conducted, it remains controversial as to how N addition affects Rs and its components [i.e., autotrophic (Ra) and heterotrophic respiration (Rh)]. To reconcile the difference, we conducted a comprehensive meta‐analysis of 295 published studies to examine the responses of Rs and its components to N addition in terrestrial ecosystems. We also assessed variations in their responses in relation to ecosystem types, environmental conditions, and experimental duration (DUR). Our results show that N addition significantly increased Rs by 2.0% across all biomes but decreased by 1.44% in forests and increased by 7.84% and 12.4% in grasslands and croplands, respectively (P < 0.05). The differences may largely result from diverse responses of Ra to N addition among biomes with more stimulation of Ra in croplands and grasslands compared with no significant change in forests. Rh exhibited a similar negative response to N addition among biomes except that in croplands, tropical and boreal forests. Methods of partitioning Rs did not induce significant differences in the responses of Ra or Rh to N addition, except that Ra from root exclusion and component integration methods exhibited the opposite responses in temperate forests. The response ratios (RR) of Rs to N addition were positively correlated with mean annual temperature (MAT), with being more significant when MAT was less than 15 °C, but negatively with DUR. In addition, the responses of Rs and its components to N addition largely resulted from the changes in root and microbial biomass and soil C content as indicated by correlation analysis. The response patterns of Rs to N addition as revealed in this study can be benchmarks for future modeling and experimental studies.
Heat and Solute Tracers: How Do They Compare in Heterogeneous Aquifers?
Authors: Irvine Dylan J. , Simmons Craig T. , Werner Adrian D. , Graf Thomas 
Published: December 2013

AbstractA comparison of groundwater velocity in heterogeneous aquifers estimated from hydraulic methods, heat and solute tracers was made using numerical simulations. Aquifer heterogeneity was described by geostatistical properties of the Borden, Cape Cod, North Bay, and MADE aquifers. Both heat and solute tracers displayed little systematic under‐ or over‐estimation in velocity relative to a hydraulic control. The worst cases were under‐estimates of 6.63% for solute and 2.13% for the heat tracer. Both under‐ and over‐estimation of velocity from the heat tracer relative to the solute tracer occurred. Differences between the estimates from the tracer methods increased as the mean velocity decreased, owing to differences in rates of molecular diffusion and thermal conduction. The variance in estimated velocity using all methods increased as the variance in log‐hydraulic conductivity (K) and correlation length scales increased. The variance in velocity for each scenario was remarkably small when compared to σ2ln(K) for all methods tested. The largest variability identified was for the solute tracer where 95% of velocity estimates ranged by a factor of 19 in simulations where 95% of the K values varied by almost four orders of magnitude. For the same K‐fields, this range was a factor of 11 for the heat tracer. The variance in estimated velocity was always lowest when using heat as a tracer. The study results suggest that a solute tracer will provide more understanding about the variance in velocity caused by aquifer heterogeneity and a heat tracer provides a better approximation of the mean velocity.
Occupation, Dignity, and Space: The Rise of Dalit Studies
Authors: Rawat Ramnarayan S 
Published: December 2013

AbstractDalit Studies has emerged as a new field of study in South Asia since the 1990s, helping to reorient scholarship's interest away from the study of untouchability as a phenomenon toward a recognition and recovery of Dalit actors. This review essay identifies three broad themes‐occupation, dignity, and space, and uses them to survey the literature on Dalit society over the last hundred years. It suggests that occupation was a prominent organizing category in colonial and early post‐colonial ethnographic writing that was used to catalogue and define Dalit religious traditions and socio‐economic practices. Struggles for dignity and efforts to eradicate caste inequality have become central concerns in more recent writings. This essay also draws attention to a less recognized theme by focusing on the role of space, particularly the role of jati mohallas, in mediating the experience of caste and shaping Dalit political consciousness.
Italian Liberal Imperialism in China: A Review of the State of the Field
Authors: Urosevic Uros 
Published: December 2013

AbstractThe story of Italian imperialism in China is an almost forgotten one. Few know that the Kingdom of Italy was on the verge of war with the Qing Empire in 1899 and that, following its participation in the Boxer War a year later, it acquired a concession in Tianjin, which it kept until 1947. This nearly forgotten episode is important, however, for understanding Italian imperialism as a whole. For a number of years, research of Italian imperialist past has tended to pay more attention to fascist imperialism at the expense of liberal imperialism, at times making Italian imperialism in general appear as an outgrowth of fascism. This is dangerously misleading, as it was imperialism of the liberal era that first revealed expansionistic tendencies that would characterise Italian fascism half a century later. The historical importance of Italian liberal imperialism as a precursor of fascist imperialism and an important early signal of totalitarian proclivities of Italian political elites needs, therefore, to be critically reappraised.
As Historical Subjects: The African Diaspora in Colonial Latin American History
Authors: O'Toole Rachel Sarah 
Published: December 2013

AbstractThis article celebrates and explores the current historiography on colonial Afro‐Latin Americans in the Spanish Americas to illuminate how scholars can continue to develop their methodological approaches to recuperating enslaved and free agency. Drawing on Michel‐Rolph Trouillot's distinction between historical actors and purposeful subjects, the essay suggests that even within slavery, men and women of African descent were able to contest slaveholding, develop their own standards within racial hierarchies, claim subject positions as Catholics, and lay claim to freedom. By asking questions regarding African‐descent defined objectives, scholars have begun to allow Africans and their descendants to articulate interior selves.
The Albigensian Crusade in Anglo‐American Historiography, 1888–2013
Authors: Marvin Laurence W. 
Published: December 2013

AbstractOf all the crusades which occurred in the crusade era, the Albigensian Crusade stands as one of the most infamous, although the Cathar religion and the Inquisition have drawn more academic and popular attention. Older scholarship treated the Albigensian Crusade as ancillary to the development of the Inquisition. Assigning the relative importance of the Albigensian Crusade within wider crusade historiography remains problematic for historians. An important historiographical development began in the 1970s as Anglo‐American scholars chose to treat the Albigensian Crusade not simply as precursor of the Inquisition but as a standalone event. Besides this advancement, Anglo‐American scholars have done valuable work on regions and towns affected by the crusade and Catharism. Since 9/11 and the on‐going ‘War on Terror’, crusades to the Eastern Mediterranean still drive the historiography, but more remains to be done on the Albigensian Crusade. The local church, regional studies, biographical treatments, and prosopographical work have barely been touched on in English.