bluuebunny/crossref_metadata_2025_split huggingface dataset:
The TATA‐binding Protein DNA‐binding domain of eukaryotic parasites is a potentially druggable target
Authors: Santiago Ángel , Razo‐Hernández Rodrigo Said , Pastor Nina 
Published: October 2019

AbstractThe TATA‐binding protein (TBP) is a central transcription factor in eukaryotes that interacts with a large number of different transcription factors; thus, affecting these interactions will be lethal for any living being. In this work, we present the first structural and dynamic computational study of the surface properties of the TBP DNA‐binding domain for a set of parasites involved in diseases of worldwide interest. The sequence and structural differences of these TBPs, as compared with human TBP, were proposed to select representative ensembles generated from molecular dynamics simulations and to evaluate their druggability by molecular ensemble‐based docking of drug‐like molecules. We found that potential druggable sites correspond to the NC2‐binding site, N‐terminal tail, H2 helix, and the interdomain region, with good selectivity for Plasmodium falciparum, Necator americanus, Entamoeba histolytica, Candida albicans, and Taenia solium TBPs. The best hit compounds share structural similarity among themselves and have predicted dissociation constants ranging from nM to μM. These can be proposed as initial scaffolds for experimental testing and further optimization. In light of the obtained results, we propose TBP as an attractive therapeutic target for treatment of parasitic diseases.
Hereditary angioedema: Looking for bradykinin production and triggers of vascular permeability
Authors: Margaglione Maurizio , D’Apolito Maria , Santocroce Rosa , Maffione Angela Bruna 
Published: October 2019

AbstractSince the Osler's identification of the inherited nature of hereditary angioedema, a huge array of information was collected on pathogenetic mechanisms of the disease. Over the last years, information grew fast, and mutations in different genes, in addition to C1‐inhibitor, were found to be causative. All types are inherited as autosomal‐dominant traits with incomplete penetrance and little or no genotype‐phenotype correlation. As a result, the clinical expression is characterized by a large heterogeneity. The acknowledgement of mechanisms leading to heterogeneity of the clinical phenotype is likely to provide important information not only for a better understanding of the pathogenesis but also for therapy. Regardless of which gene is mutated, similar pathways seem to play a pivotal role, triggering the up‐regulation of contact activation system/kallikrein kinin system and giving rise to an unbalanced increase of bradykinin. However, notwithstanding the increase of bradykinin in bloodstream, the phenomenon is localized and no general vascular leakage and oedema is recognized. Thus, it is conceivable that there exist one or more localized factors that stimulate the production of bradykinin, which does not become a systemically event. Uncovering of these factors may shed lights on the missing part of the pathogenesis of hereditary angioedema. The present review, collecting information on pathogenesis from biochemical and genetics investigations, tries to provide a comprehensive view of the pathogenesis of hereditary angioedema. This can allow for a better understanding of the disease and lead to focused investigations that can further improve our knowledge.
Histamine‐induced plasticity and gene expression in corticostriatal pathway under hyperammonemia
Authors: Sergeeva Olga A. , Chepkova Aisa N. , Görg Boris , Rodrigues Almeida Filipe , Bidmon Hans‐Jürgen , Haas Helmut L. , Häussinger Dieter 
Published: October 2019

AbstractAimsHistamine H3 receptor (H3R) antagonists/inverse agonists increase vigilance. We studied brain histaminergic pathways under hyperammonemia and the transcriptome of receptors and their signaling cascades to provide a rationale for wake‐promoting therapies.MethodsWe analyzed histamine‐induced long‐lasting depression of corticostriatal synaptic transmission (LLDhist). As the expression of dopamine 1 receptors (D1R) is upregulated in LGS‐KO striatum where D1R‐H3R dimers may exist, we investigated actions of H3R and D1R agonists and antagonists. We analyzed transcription of selected genes in cortex and dorsal striatum in a mouse model of inborn hyperammonemia (liver‐specific glutamine synthetase knockout: LGS‐KO) and compared it with human hepatic encephalopathy.ResultsLGS‐KO mice showed significant reduction of the direct depression (DD) but not the long‐lasting depression (LLD) by histamine. Neither pharmacological activation nor inhibition of D1R significantly affected DDhist and LLDhist in WT striatum, while in LGS‐KO mice D1R activation suppressed LLDhist. Histaminergic signaling was found unchanged at the transcriptional level except for the H2R. A study of cAMP‐regulated genes indicated a significant reduction in the molecular signature of wakefulness in the diseased cortex.ConclusionsOur findings provide a rationale for the development of aminergic wake‐promoting therapeutics in hyperammonemic disorders.
Natural history films raise species awareness—A big data approach
Authors: Fernández‐Bellon Darío , Kane Adam 
Published: October 2019

AbstractIn urbanized societies that are increasingly disconnected from nature, communicating ecological and species awareness is crucial to revert the global environmental crisis. However, our understanding of the effectiveness of this process is limited. We present a framework for describing how such awareness may be transferred and test it on the popular BBC show Planet Earth 2 by analyzing Twitter and Wikipedia big data activity. Despite lacking explicit conservation themes, this show generated species awareness, stimulating audience engagement for information at magnitudes comparable to those achieved by other conservation‐focused campaigns. Results suggest that natural history films can provide vicarious connections to nature and can generate durable shifts in audience awareness beyond the broadcast of the show—key factors for changing environmental attitudes. More broadly, this study underscores how open‐source big data analysis can inform effective dissemination of ecological awareness and provides a framework for future research for investigating behavioral change.
De‐centring the ‘White Gaze’ of Development
Authors: Pailey Robtel Neajai 
Published: October 2019

ABSTRACTIn its crudest form, development has traditionally been about dissecting the political, socio‐economic and cultural processes of black, brown and other subjects of colour in the so‐called global South and finding them regressive, particularly in comparison to the so‐called progressive global North. However, in the midst of a 21st century, de‐colonial scholarly pivot, ‘opening up development’ fundamentally demands turning the colonial, ‘white gaze’ on its head. In particular, contemporary social media movements challenging white supremacy such as #BlackLivesMatter have gained prominence while non‐white development actors such as China have emerged as enticing alternatives. These phenomena have pried open development with both positive and negative results, intended and unintended consequences. This article seeks to put Critical Development Studies into fluid conversation with Critical Race Studies in an examination of how scholars, policy makers and practitioners have simultaneously succeeded and failed in subverting the ‘white gaze’ of development.
Combination of bisacodyl suppository and 1 L polyethylene glycol plus ascorbic acid is a non‐inferior and comfortable regimen compared to 2 L polyethylene glycol plus ascorbic acid
Authors: Kim Sun Hwa , Kim Eun Ran , Kim Kyunga , Kim Tae Jun , Hong Sung Noh , Chang Dong Kyung , Kim Young‐Ho 
Published: October 2019

Background and AimAppropriate bowel cleansing before colonoscopy is an important factor in increasing the detection rate of lesions. Low‐volume polyethylene glycol (PEG) plus ascorbic acid (PEG‐Asc) reduces the dosage of bowel preparation agent, but still presents discomfort to patients. The primary aim of the present study was to compare the efficacy of bowel cleansing between 2 L PEG‐Asc (control) and 1 L PEG‐Asc with bisacodyl suppository (suppository) groups, and the secondary aim was to investigate complications and tolerability between the two groups.MethodsThis was a single‐center prospective randomized controlled study. We identified 168 patients scheduled for colonoscopy between August 2017 and January 2018 and randomly assigned them to the control or to the suppository groups. Efficacy of bowel cleansing was assessed using the Boston Bowel Preparation Scale (BBPS), and side‐effects were surveyed using questionnaires.ResultsNo significant difference was detected in baseline characteristics including insertion and withdrawal times, and adenoma detection rates between the two groups. Total BBPS score was 7.93 ± 1.06 and 7.74 ± 1.02 in the control and suppository groups, respectively (P = 0.22). Incidence of abdominal pain and nausea was not statistically different, whereas that of sleep disturbance and anal discomfort was higher in the control group. (P = 0.00).ConclusionsOne liter PEG‐Asc with bisacodyl suppository resulted in an equivalent bowel‐cleansing outcome with reduced patient discomfort compared to 2 L PEG‐Asc. Therefore, PEG‐Asc with bisacodyl suppository represents a potential alternative and increases patient compliance with bowel preparation.
Nicotinamide N‐methyltransferase in nonmelanoma skin cancers
Authors: Pompei Veronica , Salvolini Eleonora , Rubini Corrado , Lucarini Guendalina , Molinelli Elisa , Brisigotti Valerio , Pozzi Valentina , Sartini Davide , Campanati Anna , Offidani Annamaria , Emanuelli Monica 
Published: October 2019

AbstractBackgroundSquamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent the most common forms of nonmelanoma skin cancers (NMSCs). Although successful treatment of these neoplasms is based on surgical excision, an increasing number of BCCs relapses and many SCCs display high rates of recurrence and metastasis. Nicotinamide N‐methyltransferase (NNMT) is a cytosolic enzyme, which was found to be upregulated in different solid tumours. However, there are no data regarding enzyme expression in NMSCs. The aim of this study was therefore to evaluate the potential involvement of NNMT in BCCs and SCCs.Materials and methodsImmunohistochemical analyses were carried out on 40 BCC cases and 39 SCC cases, to evaluate enzyme expression in tumour and surrounding healthy margins. Moreover, the relationship between NNMT intratumour levels and clinico‐pathological parameters were explored.ResultsNicotinamide N‐methyltransferase was found to be overexpressed in BCCs compared with control tissues, while a significant enzyme downregulation was detected in SCCs with respect to corresponding healthy margins. In addition, NNMT levels were negatively related to aggressiveness of both BCCs (distinguishing between infiltrative and nodular tumours) and SCCs (considering head and neck forms and tumours of the extremities and trunk).ConclusionsThese evidences seem to demonstrate that the different NNMT dysregulation detected in BCC and SCC may be the result of important biological traits distinctively characterizing these two forms within NMSCs. In addition, enzyme levels seem to be inversely correlated with tumour aggressiveness, thus suggesting the potential suitability of the enzyme as a prognostic biomarker for both neoplasms.
Knowledge about nanotechnology and intention to use nanomaterials: A comparative study among dental students in Norway and Romania
Authors: Xenaki Victoria , Marthinussen Mihaela Cuida , Costea Daniela Elena , Didilescu Andreea Cristiana , Susin Cristiano , Cimpan Mihaela Roxana , Åstrøm Anne Nordrehaug 
Published: October 2019

AbstractBackgroundThe introduction of innovative nanotechnologies in medicine and dentistry may initiate a need for curriculum revision at the universities. The aim of this study was to assess dental students’ knowledge and attitudes related to nanotechnology. Covariates of students' intention to use nanomaterials in their future dental practice were evaluated using the theory of planned behaviour (TPB).MethodsDental students at Norwegian and Romanian Universities were invited to participate. A self‐administered structured questionnaire including socio‐demographics and Ajzen's TPB components was used.FindingsA total of 212 out of 732 dental students participated in the survey: 52 Norwegian and 160 Romanian. Most students reported to have little knowledge about nanotechnology (Norwegians = 44.2% vs Romanians = 46.9%, P < .05). More than 90% of the students in both countries reported that they wanted to get more information about nanotechnology. Mean knowledge score was similar for Norwegian and Romanian students (4.4 ± 1.7 vs 4.2 ± 1.4, P > .05). Romanian students had more positive attitude, stronger subjective norms and stronger perceived behavioural control towards nanotechnology compared to their Norwegian counterparts. Intention to use nanomaterials in the total sample was most strongly influenced by attitude towards the use of dental nanomaterials (beta = 0.42, P < .001).ConclusionDental students in Norway and Romania demonstrated limited knowledge about nanotechnology. Intention to use nanomaterials was primarily influenced by attitudes. A clear desire for more information about the application of nanotechnology in dentistry was expressed by the respondents indicating a need for curriculum modification.
Poor patient awareness and frequent misdiagnosis of migraine: findings from a large transcontinental cohort
Authors: Viana M. , Khaliq F. , Zecca C. , Figuerola M. D. L. , Sances G. , Di Piero V. , Petolicchio B. , Alessiani M. , Geppetti P. , Lupi C. , Benemei S. , Iannacchero R. , Maggioni F. , Jurno M. E. , Odobescu S. , Chiriac E. , Marfil A. , Brighina F. , Barrientos Uribe N. , Pérez Lago C. , Bordini C. , Lucchese F. , Maffey V. , Nappi G. , Sandrini G. , Tassorelli C. 
Published: October 2019

Background and purposeAlthough migraine is the second most disabling condition worldwide, there is poor awareness of it. The objective was to assess the awareness of migraine and previous diagnostic and therapeutic consultations and treatments in a large international population of migraineurs.MethodsThis was a multicentre study conducted in 12 headache centres in seven countries. Each centre recruited up to 100 patients referred for a first visit and diagnosed with migraine. Subjects were given a structured clinical questionnaire‐based interview about the perceptions of the type of headache they suffered from, its cause, previous diagnoses, investigations and treatments.ResultsIn all, 1161 patients completed the study. Twenty‐eight per cent of participants were aware that they suffered from migraine. Sixty‐four per cent called their migraine ‘headache'; less commonly they used terms such as ‘cervical pain' (4%), tension headache (3%) and sinusitis (1%). Eight per cent of general practitioners and 35% of specialists (of whom 51% were neurologists and/or headache specialists) consulted for migraine formulated the correct diagnosis. Before participating in the study, 50% of patients had undergone X‐ray, computed tomography and/or magnetic resonance imaging of the cervical spine and 76% underwent brain and/or cervical spine imaging for migraine. Twenty‐eight per cent of patients had received symptomatic migraine‐specific medications and 29% at least one migraine preventive medication.ConclusionsAlthough migraine is a very common disease, poor awareness of it amongst patients and physicians is still an issue in several countries. This highlights the importance of the promotion of migraine awareness to reduce its burden and limit direct and indirect costs and the risk of exposure to useless investigations.
Evoked potentials can predict future disability in people with clinically isolated syndrome
Authors: Crnošija L. , Gabelić T. , Barun B. , Adamec I. , Krbot Skorić M. , Habek M. 
Published: October 2019

Background and purposeThe aim was to evaluate whether the addition of evoked potentials (EPs) which evaluate brainstem function to the EP score improves its ability to predict disease progression in people with clinically isolated syndrome (pwCIS).MethodsFor 94 pwCIS, data on disease activity and progression after 2.9 (1.4–4.1) years of follow‐up were available. Baseline characteristics included magnetic resonance imaging (MRI) parameters, visual EPs, auditory EPs, somatosensory EPs of the median and tibial nerves, vestibular evoked myogenic potentials and tongue somatosensory EPs.ResultsA multivariable regression model including age, sex, total number of T2 lesions on baseline MRI and EP score >13 showed that the total number of T2 lesions on baseline MRI and EP score >13 increase the likelihood for sustained accumulation of disability (SAD). After controlling for age, sex and the total number of T2 lesions on baseline MRI, the hazard of SAD for participants with EP score >13 is 4.093 times that of participants with EP score ≤13. EP score >13 also increases the likelihood for progression measured with a composite measure of progression which uses the Expanded Disability Status Scale, the nine‐hole peg test and the timed 25‐ft walk (exp(B) = 5.577, 95% confidence interval 1.520–20.468, P = 0.01).ConclusionThe addition of EPs that evaluate brainstem function to the EP score enables prediction of the progression of disability in pwCIS.
Exploring One's Family Heritage to Enhance Self‐awareness: A Step Toward Developing Cultural Competence
Authors: Desai Priti P. , Dodor Bernice A. , Carroll Elizabeth B. 
Published: October 2019

ObjectiveTo examine the effectiveness of a writing assignment that required undergraduate students in a diversity course to explore their family heritage. The purpose of this assignment was to increase self‐awareness of students regarding how structural characteristics of ethnicity, race, social class, and religion shaped the contributions family made to their emerging values, beliefs, and attitudes about interacting with others.BackgroundInstructors for family diversity courses need more instructional strategies that foster self‐awareness, which is commonly identified as a first step toward developing cultural competency. One such strategy is described in this paper.MethodA mixed method approach was employed, with both quantitative analysis of the frequency of responses from a course effectiveness survey and a descriptive narrative analysis of the text contained in 36 students' family heritage reflective papers.ResultsMost students reported increased self‐awareness of their family history, racial and ethnic identity, role of social class and religion on socialization, and acknowledged contextual experiences of privilege or discrimination.ConclusionOur findings suggest that most students deepened their understanding of personal assumptions. They recognized the need to remain open to understanding and showing more empathy toward individuals from diverse backgrounds.ImplicationsOur results highlight the opportunity for instructors to be intentional in sequencing instructional activities, promoting respectful peer‐driven learning and dialogue, recognizing students' worldview, and being open to faculty development opportunities.
Biological and ecological aspects of the deep‐water red crab populations inhabiting isolated seamounts to the west of the Azores (Mid‐Atlantic Ridge)
Authors: Santos Régis , Pinho Mário , Melo Octávio , Gonçalves João , Leocádio Ana , Aranha Ana , Menezes Gui , Isidro Eduardo 
Published: October 2019

AbstractSeamounts are common topographic features in the Mid‐Atlantic Ridge (MAR) including the Azores. However, the knowledge on the ecology of seamounts in this region remains scarce despite needs for assessment and management of seamount resources such as the developing fisheries for deep‐water crabs. We described here for the first time the biological characteristics of an unexploited virgin deep‐water red crab Chaceon affinis population on seamount areas of the MAR to test the hypothesis that its general life history characteristics are similar in different ecosystem types (coastal areas and seamounts) across Macaronesia. We used a randomly stratified design to prospect a layer between 600 and 900 m depth around the summit of two isolated seamounts off the Azores. Results were consistent with the literature information in relation to the patterns of depth distribution, size and sex structure, and reproductive aspects. On the other hand, seamounts showed higher abundances when compared to previously studied coastal areas. Abundance may be also different between seamount areas as a function of the suitable bottom type available and presence of hydrothermal vents. We recommend that the essential habitat of the species should be better mapped identifying vulnerable areas before the development of any fishery.
Extreme spatial heterogeneity in carbonate accretion potential on a Caribbean fringing reef linked to local human disturbance gradients
Authors: de Bakker Didier M. , van Duyl Fleur C. , Perry Chris T. , Meesters Erik H. 
Published: October 2019

AbstractThe capacity of coral reefs to maintain their structurally complex frameworks and to retain the potential for vertical accretion is vitally important to the persistence of their ecological functioning and the ecosystem services they sustain. However, datasets to support detailed along‐coast assessments of framework production rates and accretion potential do not presently exist. Here, we estimate, based on gross bioaccretion and bioerosion measures, the carbonate budgets and resultant estimated accretion rates (EAR) of the shallow reef zone of leeward Bonaire – between 5 and 12 m depth – at unique fine spatial resolution along this coast (115 sites). Whilst the fringing reef of Bonaire is often reported to be in a better ecological condition than most sites throughout the wider Caribbean region, our data show that the carbonate budgets of the reefs and derived EAR varied considerably across this ~58 km long fringing reef complex. Some areas, in particular the marine reserves, were indeed still dominated by structurally complex coral communities with high net carbonate production (>10 kg CaCO3 m−2 year−1), high live coral cover and complex structural topography. The majority of the studied sites, however, were defined by relatively low budget states (<2 kg CaCO3 m−2 year−1) or were in a state of net erosion. These data highlight the marked spatial heterogeneity that can occur in budget states, and thus in reef accretion potential, even between quite closely spaced areas of individual reef complexes. This heterogeneity is linked strongly to the degree of localized land‐based impacts along the coast, and resultant differences in the abundance of reef framework building coral species. The major impact of this variability is that those sections of reef defined by low‐accretion rates will have limited capacity to maintain their structural integrity and to keep pace with current projections of climate change induced sea‐level rise (SLR), thus posing a threat to reef functioning and biodiversity, potentially leading to trophic cascades. Since many Caribbean reefs are more severely degraded than those found around Bonaire, it is to be expected that the findings presented here are rather the rule than the exception, but the study also highlights the need for similar high spatial resolution (along‐coast) assessments of budget states and accretion rates to meaningfully explore increasing coastal risk at the country level. The findings also more generally underline the significance of reducing local anthropogenic disturbance and restoring framework building coral assemblages. Appropriately focussed local preservation efforts may aid in averting future large‐scale above reef water depth increases on Caribbean coral reefs and will limit the social and economic implications associated with the loss of reef goods and services.