bluuebunny/crossref_metadata_2025_split huggingface dataset:
Refusal as political practice:
Authors: McGRANAHAN CAROLE 
Published: August 2018

ABSTRACTIs it possible to be both a refugee and a citizen? For six decades, Tibetan refugees have refused citizenship in South Asia as part of their claims to Tibetan state sovereignty. They have lived in India and Nepal as refugee noncitizens, either undocumented or underdocumented, for multiple generations. But as Tibetans migrate to the United States and Canada, they gain citizenship through political asylum while maintaining their belonging to the Dalai Lama's refugee community. This shift in political practice is as situated in specific histories as it is in geographies. Tibetan citizenship practices in exile are not claims for recognition or forms of resistance; they are, rather, a refusal of international norms through a present‐day insistence on past and future political sovereignty.
Risk of repeat cesarean delivery in women undergoing trial of labor: A population‐based cohort study
Authors: Lindblad Wollmann Charlotte , Ahlberg Mia , Saltvedt Sissel , Johansson Kari , Elvander Charlotte , Stephansson Olof 
Published: August 2018

AbstractIntroductionThe aim of this study was to consult women on best mode of delivery after a first cesarean section, more knowledge regarding risk for a repeat unplanned cesarean is needed. We investigated the association between indication of first cesarean and cervical dilation during labor preceding the first cesarean and risk of repeat cesarean in women undergoing trial of labor.Material and methodsA population‐based cohort study using electronic medical records of all women delivering in the Stockholm‐Gotland region, Sweden, between 2008 and 2014. The population consisted of 3116 women with a first cesarean undergoing a trial of labor with a singleton infant in cephalic presentation at ≥37 weeks of gestation. Relative risks (RR) with 95% CI were estimated using Poisson regression analyses.ResultsWomen with a first unplanned cesarean had higher risk of repeat cesarean compared with women with elective first cesarean (35.7% vs 20.7%, adjusted RR 1.64, 95% CI 1.43‐1.89). In women with a cesarean due to dystocia, increasing cervical dilation in first labor decreased the risk of repeat cesarean in second labor. The adjusted RR of repeat cesarean was 2.48 with dilation ≤5 cm, 1.98 with dilation 6‐10 cm, and 1.46 if fully dilated.ConclusionsAlmost 70% of all women eligible for trial of labor after cesarean had a vaginal birth, even women with a history of labor dystocia had a good chance of success. A greater cervical dilation in the first delivery ending with a cesarean was not in vain, since the chance of vaginal birth in the subsequent delivery increased with greater dilation.
Optimal introduction of laparoscopic liver resection for Child–Pugh B
Authors: Fuji Hiroaki , Seo Satoru , Toda Rei , Yoh Tomoaki , Ikeno Yoshinobu , Fukumitsu Ken , Ishii Takamichi , Taura Kojiro , Hatano Etsuro , Kaido Toshimi , Uemoto Shinji 
Published: August 2018

AbstractIntroductionSurgery for Child–Pugh B liver function is considered risky because of its high morbidity rate and the acceptable indication criteria for laparoscopic liver resection (LLR) for Child–Pugh B patients have not been identified. We conducted a retrospective cohort study to determine the optimal introduction of LLR for Child–Pugh B patients based on our single‐institute experience.MethodsA total of 17 Child–Pugh B patients underwent LLR between 2005 and 2017. Their clinical outcomes were compared to those of LLR for Child–Pugh A patients (103 cases), conventional open liver resection for Child–Pugh B patients (19 cases), and radiofrequency ablation (RFA) for Child–Pugh B patients (20 cases) during the same period.ResultsLLR for Child–Pugh B patients had a significantly higher conversion rate than LLR for Child–Pugh A patients (Child–Pugh A vs B: 3.9% vs 35.3%, P < 0.01). However, patients who successfully underwent laparoscopic resection (11 cases) had fewer postoperative ascites and shorter postoperative hospital stays compared to patients who underwent conventional open liver resection. In comparison to the RFA group, the LLR group more frequently had lesions in the left lateral segment (LLR vs RFA: 50.0% vs 10.0%, P = 0.02) and exophytic tumor (21.4% vs 0%, P = 0.02) than did the RFA group. Also, compared to the RFA group, the LLR group had a lower local recurrence rate (0% vs 15%, P = 0.25) and a longer recurrence‐free survival (P = 0.049), but the overall survival was similar between the two groups.ConclusionsIn the treatment of Child–Pugh B liver malignancy, the minimal invasiveness of LLR was revealed. Our results suggest that lesions in the left lateral segment and exophytic tumors are good indications for LLR for Child–Pugh B.
Examining the use of e‐assessment in higher education: teachers and students’ viewpoints
Authors: Rolim Catarina , Isaias Pedro 
Published: August 2018

AbstractThe combination of teaching and information technologies is at the origin of a more embracing, flexible and accessible approach to learning. Assessment is considered an integral part of the learning process, but it has always been considered challenging for teachers. Through the adoption of information technologies, it is possible to create new opportunities to improve assessment. Despite its numerous advantages, e‐assessment remains a topic of much discussion for many, due to doubts that arise about its efficiency and effectiveness. In order to understand this issue, this study aims to explore e‐assessment in higher education, from the viewpoint of teachers and students. Four online surveys were distributed among teachers and students in Portugal and other countries. While the results show that Portugal is slightly behind in terms of adoption, there is a strong awareness of the importance of e‐assessment. Internationally, e‐assessment has higher adoption rates, and both teachers and students believe that this method of assessment is advantageous.
Measuring the effects of α1‐antitrypsin polymerisation on the structure and biophysical properties of the endoplasmic reticulum
Authors: Chambers Joseph E. , Dickens Jennifer A. , Marciniak Stefan J. 
Published: August 2018

AbstractAn important function of the endoplasmic reticulum (ER) is to serve as a site of secretory protein folding. When the accumulation of misfolded proteins threatens to disturb luminal homoeostasis, the cell is said to experience ER stress. By contrast, the accumulation of well‐folded proteins inside the ER leads to a distinct form of strain called ER overload. The serpins comprise a large family of proteins whose folding has been studied in great detail. Some mutant serpins misfold to cause ER stress, whereas others fold but then polymerise to cause ER overload. We discuss recent advances in the use of dynamic fluorescence imaging to study these phenomena. We also discuss a new technique that we recently published, rotor‐based organelle viscosity imaging (ROVI), which promises to shed more light on the biophysical features of ER stress and ER overload.
The polyphenol resveratrol promotes skeletal growth in mice through a sirtuin 1‐bone morphogenic protein 2 longevity axis
Authors: Zhao Ming , Ko Seon‐Yle , Garrett I Ross , Mundy Gregory R , Gutierrez Gloria E , Edwards James R 
Published: August 2018

Background and PurposeThe polyphenol resveratrol (RSV) exists in high quantities in certain foods (e.g. grapes and nuts). However, the capacity of RSV to confer physiological health benefits and a biological mechanism through which this might occur remains unclear.Experimental ApproachAged, RSV‐treated (300 mg·kg−1·day−1) and genetically modified [endothelial NOS (eNOS−/−)] female mice were assessed using histomorphometric and μCT analysis. Alongside in vivo analysis, molecular siRNA knockdown and pharmacological manipulation of eNOS, BMP2 and sirtuin 1 (SIRT1) and functional cellular assays in an osteoblast cell line panel, explored the mechanism through which RSV might impact overall bone volume.Key ResultsRSV promoted osteoblast activity and bone growth in vivo. RSV dose‐dependently and simultaneously increased alkaline phosphatase (ALP) and eNOS levels. Similarly, NO‐donor treatment increased ALP, runt homology transcription factor 2, BMP2 and stimulated bone formation, whilst eNOS‐deficient mice displayed a bone loss phenotype. Moreover, RSV‐induced increase in ALP and BMP2 expression was blocked in eNOS−/− osteoblasts and by BMP‐inhibitor noggin. The longevity‐linked SIRT1 enzyme was positively regulated by RSV and SIRT1 deletion reduced eNOS, BMP2 and ALP. Like eNOS deletion, loss of SIRT1 blocked RSV‐induced osteoblast activity; however, SIRT1 levels remained unchanged in eNOS−/− mice, indicating RSV activation of SIRT1 stimulates BMP2 release via eNOS. This signalling axis is supported by decreased SIRT1, eNOS and BMP2 confirmed in old versus young bone.Conclusions and ImplicationsThese findings suggest a new mechanism of action in bone remodelling and the ageing skeleton, where RSV positively impacts bone homeostasis via SIRT1 activation of BMP2.
Brain histamine modulates recognition memory: possible implications in major cognitive disorders
Authors: Provensi Gustavo , Costa Alessia , Izquierdo Ivan , Blandina Patrizio , Passani Maria Beatrice 
Published: August 2018

Several behavioural tests have been developed to study and measure emotionally charged or emotionally neutral memories and how these may be affected by pharmacological, dietary or environmental manipulations. In this review, we describe the experimental paradigms used in preclinical studies to unravel the brain circuits involved in the recognition and memorization of environmentally salient stimuli devoid of strong emotional value. In particular, we focus on the modulatory role of the brain histaminergic system in the elaboration of recognition memory that is based on the judgement of the prior occurrence of an event, and it is believed to be a critical component of human declarative memory. The review also addresses questions that may help improve the treatment of impaired declarative memory described in several affective and neuropsychiatric disorders such as ADHD, Alzheimer's disease and major neurocognitive disorder.Linked ArticlesThis article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc
Cysteine residues in mitochondrial intermembrane space proteins: more than just import
Authors: Habich Markus , Salscheider Silja Lucia , Riemer Jan 
Published: August 2018

The intermembrane space (IMS) is a very small mitochondrial sub‐compartment with critical relevance for many cellular processes. IMS proteins fulfil important functions in transport of proteins, lipids, metabolites and metal ions, in signalling, in metabolism and in defining the mitochondrial ultrastructure. Our understanding of the IMS proteome has become increasingly refined although we still lack information on the identity and function of many of its proteins. One characteristic of many IMS proteins are conserved cysteines. Different post‐translational modifications of these cysteine residues can have critical roles in protein function, localization and/or stability. The close localization to different ROS‐producing enzyme systems, a dedicated machinery for oxidative protein folding, and a unique equipment with antioxidative systems, render the careful balancing of the redox and modification states of the cysteine residues, a major challenge in the IMS. In this review, we discuss different functions of human IMS proteins, the involvement of cysteine residues in these functions, the consequences of cysteine modifications and the consequences of cysteine mutations or defects in the machinery for disulfide bond formation in terms of human health.Linked ArticlesThis article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc
The bidirectional interaction between the sympathetic nervous system and immune mechanisms in the pathogenesis of hypertension
Authors: Carnagarin Revathy , Matthews Vance , Zaldivia Maria T K , Peter Karlheinz , Schlaich Markus P 
Published: August 2018

Over the last few years, evidence has accumulated to suggest that hypertension is, at least in part, an immune‐mediated inflammatory disorder. Many links between immunity and hypertension have been established and provide a complex framework of mechanistic interactions contributing to the rise in BP. These include immune‐mediated inflammatory processes affecting regulatory brain nuclei and interactions with other mediators of cardiovascular regulation such as the sympathetic nervous system. Sympathoexcitation differentially regulates T‐cells based upon activation status of the immune cell as well as the resident organ. Exogenous and endogenous triggers activate signalling pathways in innate and adaptive immune cells resulting in pro‐inflammatory cytokine production and activation of T‐lymphocytes in the cardiovascular and renal regions, now considered major factors in the development of essential hypertension. The inflammatory cascade is sustained and exacerbated by the immune flow via the brain–bone marrow–spleen–gastrointestinal axis and thereby further aggravating immune‐mediated pathways resulting in a vicious cycle of established hypertension and target organ damage. This review summarizes the evidence and recent advances in linking immune‐mediated inflammation, sympathetic activation and their bidirectional interactions with the development of hypertension.Linked ArticlesThis article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Contribution of the commensal microbiota to atherosclerosis and arterial thrombosis
Authors: Kiouptsi Klytaimnistra , Reinhardt Christoph 
Published: August 2018

The commensal gut microbiota is an environmental factor that has been implicated in the development of cardiovascular disease. The development of atherosclerotic lesions is largely influenced not only by the microbial‐associated molecular patterns of the gut microbiota but also by the meta‐organismal trimethylamine N‐oxide pathway. Recent studies have described a role for the gut microbiota in platelet activation and arterial thrombosis. This review summarizes the results from gnotobiotic mouse models and clinical data that linked microbiota‐induced pattern recognition receptor signalling with atherogenesis. Based on recent insights, we here provide an overview of how the gut microbiota could affect endothelial cell function and platelet activation, to promote arterial thrombosis.Linked ArticlesThis article is part of a themed section on When Pharmacology Meets the Microbiome: New Targets for Therapeutics? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.24/issuetoc
Setting a patient‐centered research agenda for cerebral palsy: a participatory action research initiative
Authors: Gross Paul H , Bailes Amy F , Horn Susan D , Hurvitz Edward A , Kean Jacob , Shusterman Michele ,   For the cerebral palsy research network
Published: August 2018

AimTo establish a patient‐centered research agenda for cerebral palsy (CP).MethodWe engaged a large cross‐section of the extended community of people living with CP and those providing healthcare to people with CP (‘the community’) in an educational series and collaborative survey platform to establish an initial list of prioritized research ideas. After online workshops, a facilitated Delphi process was used to select the 20 highest priorities. Select participants attended an in‐person workshop to provide comment and work toward consensus of research priorities.ResultsA research agenda for CP was developed by the community, which included consumers, clinicians, and researchers interested in advancing the established research agenda. The results included the top 16 research concepts produced by the process to shape and steward the research agenda, and an engaged cross‐section of the community.InterpretationIt has been shown that proactively engaging consumers with clinical researchers may provide more meaningful research for the community. This study suggests that future research should have more focus on interventions and outcomes across the lifespan with increased emphasis on the following outcome measures: function, quality of life, and participation.What this paper adds

A patient‐centered research agenda for cerebral palsy was established.

Comparative effectiveness of interventions, physical activity, and understanding ageing were leading themes.

Longitudinal studies across the lifespan, clinical spectrum, and ages were highly ranked.

Participants reported high value for participation outcomes.

Participants reported great appreciation for the engagement between consumers and clinician researchers.
Patient‐reported outcomes are worse for progressive‐onset multiple sclerosis than relapse‐onset multiple sclerosis, particularly early in the disease process
Authors: Zhang Y. , Taylor B. V. , Simpson S. , Blizzard L. , van der Mei I. 
Published: August 2018

Background and purposeTreatments for progressive‐onset multiple sclerosis (MS) are lacking. To improve the disease management for progressive‐onset MS, the differences between relapse‐onset MS and progressive‐onset MS in patient‐reported disability, progression and symptoms were examined.MethodsA total of 1985 participants of the Australian Multiple Sclerosis Longitudinal Study were included. Associations between onset type and outcomes were assessed with negative binomial regression.ResultsThe severity of 17 of the 19 outcomes was significantly higher for progressive‐onset MS patients than relapse‐onset MS patients, including perspectives from disability, progression over the last year, fatigue, sensory, walking difficulties, pain, balance, spasticity, sexual dysfunction, bladder, bowel, anxiety, depression and the European quality of life (EQ‐5D) (P < 0.05; adjusted mean ratio ranged from 1.11 to 1.52). The differences between the two onset types were most pronounced early in the disease process and reduced with increasing MS duration, and the interaction was significant for disability, progression over the last year, walking difficulties, bladder problems, bowel problems and spasticity.ConclusionParticipants with progressive‐onset MS were significantly worse off on nearly all patient‐reported outcomes than relapse‐onset MS participants, and the differences were most pronounced early in the disease course, highlighting the importance of early intervention for those with progressive‐onset MS.
SLC6A1variants identified in epilepsy patients reduce γ‐aminobutyric acid transport
Authors: Mattison Kari A. , Butler Kameryn M. , Inglis George Andrew S. , Dayan Oshrat , Boussidan Hanna , Bhambhani Vikas , Philbrook Bryan , da Silva Cristina , Alexander John J. , Kanner Baruch I. , Escayg Andrew 
Published: August 2018

SummaryPrevious reports have identifiedSLC6A1variants in patients with generalized epilepsies, such as myoclonic‐atonic epilepsy and childhood absence epilepsy. However, to date, none of the identifiedSLC6A1variants has been functionally tested for an effect onGAT‐1 transporter activity. The purpose of this study was to determine the incidence ofSLC6A1variants in 460 unselected epilepsy patients and to evaluate the impact of the identified variants on γ‐aminobutyric acid (GABA)transport. Targeted resequencing was used to screen 460 unselected epilepsy patients for variants inSLC6A1. Five missense variants, one in‐frame deletion, one nonsense variant, and one intronic splice‐site variant were identified, representing a 1.7% diagnostic yield. Using a [3H]‐GABAtransport assay, the seven identified exonic variants were found to reduceGABAtransport activity. A minigene splicing assay revealed that the splice‐site variant disrupted canonical splicing of exon 9 in themRNAtranscript, leading to premature protein truncation. These findings demonstrate thatSLC6A1is an important contributor to childhood epilepsy and that reducedGAT‐1 function is a common consequence of epilepsy‐causingSLC6A1variants.
Do children with Dravet syndrome continue to benefit from stiripentol for long through adulthood?
Authors: Chiron Catherine , Helias Marie , Kaminska Anna , Laroche Cecile , de Toffol Bertrand , Dulac Olivier , Nabbout Rima , An Isabelle 
Published: August 2018

SummaryObjectiveTo evaluate continuing stiripentol treatment in adulthood in Dravet syndrome (DS).MethodLongitudinal data were collected from the last visit prior to age 15 years (V15 y) to the last visit in adulthood (Vadult) in the 40 DS patients (32 typical, eight atypical) of a French historical cohort (Paris) of subjects who continued stiripentol from childhood or adolescence to adulthood.ResultsAt Vadult (18‐40 years, median = 23 years), all the patients were still receiving stiripentol (exposure = 3‐24 years, median = 18 years), associated with clobazam (40/40), valproate (39/40), and topiramate (21/40). Between V15 y and Vadult, stiripentol was interrupted in five patients (two for adverse events) but reintroduced following seizure aggravation. Loss of appetite affected 15 of 40 patients but resolved after reducing the dose of stiripentol or valproate; no other new stiripentol‐related adverse events were reported. Mean stiripentol dose was progressively decreased from 39 to 25 mg/kg/d (P = 0.0002), whereas clobazam (0.27 mg/kg/d) and valproate (14 mg/kg/d) remained stable. At Vadult, 37 of 40 patients still had generalized tonic–clonic seizures, but none still had status epilepticus (vs three at V15 y) and only one had myoclonia. During adulthood, generalized tonic–clonic seizure frequency and duration continued to decrease (P = 0.02, P = 0.008) and 10 patients experienced seizure‐free periods ≥ 1 years (up to 5 years). All patients already had intellectual disability at V15 y, but retardation was more severe at Vadult (P = 0.03). Furthermore, neurological/gait condition had declined (two patients became bedridden) and behavior had worsened (P < 0.0002). Nevertheless, the 33 patients on stiripentol from infancy/childhood (<15 years) tended to have better seizure outcome in midadulthood than the seven treated from adolescence (>15 years) and the DS patients treated from adult age or stiripentol‐naive subjects reported in the literature.SignificanceThe efficacy and safety of the stiripentol/valproate/clobazam combination started at pediatric age are maintained at very long term during adulthood. Such prolonged stiripentol therapy tends to positively impact the late prognosis of epilepsy, especially when initiated before adolescence.