bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters—a randomized, double‐blind, placebo‐controlled trial
Authors: Detyniecki Kamil , Van Ess Peter J. , Sequeira David J. , Wheless James W. , Meng Tze‐Chiang , Pullman William E. 
Published: May 2019

AbstractObjectiveTo evaluate the safety and efficacy of a novel formulation of midazolam administered as a single‐dose nasal spray (MDZ–NS) in the outpatient treatment of patients experiencing seizure clusters (SCs).MethodsThis was a phase III, randomized, double‐blind, placebo‐controlled trial (ClinicalTrials.gov NCT01390220) with patients age ≥12 years on a stable regimen of antiepileptic drugs. Following an in‐clinic test dose phase (TDP), patients entered an outpatient comparative phase (CP) and were randomized (2:1) to receive double‐blind MDZ–NS 5 mg or placebo nasal spray, administered by caregivers when they experienced an SC. The primary efficacy end point was treatment success (seizure termination within 10 minutes and no recurrence 10 minutes to 6 hours after trial drug administration). Secondary efficacy end points were proportion of patients with seizure recurrence 10 minutes to 4 hours, and time‐to‐next seizure >10 minutes after double‐blind drug administration. Safety was monitored throughout.ResultsOf 292 patients administered a test dose, 262 patients were randomized, and 201 received double‐blind treatment for an SC (n = 134 MDZ–NS, n = 67 placebo, modified intent‐to‐treat population). A significantly greater proportion of MDZ–NS‐ than placebo‐treated patients achieved treatment success (53.7% vs 34.4%; P = 0.0109). Significantly, fewer MDZ–NS‐ than placebo‐treated patients experienced seizure recurrence (38.1% vs 59.7%; P = 0.0043). Time‐to‐next seizure analysis showed early separation (within 30 minutes) between MDZ–NS and placebo that was maintained throughout the 24‐hour observation period (21% difference at 24 hours; P = 0.0124). Sixteen patients (5.5%) discontinued because of a treatment‐emergent adverse event (TEAE) during the TDP and none during the CP. During the CP, 27.6% and 22.4% of patients in the MDZ–NS and placebo groups, respectively, experienced ≥1 TEAE.SignificanceMDZ–NS was superior to placebo in providing rapid, sustained seizure control when administered to patients experiencing an SC in the outpatient setting and was associated with a favorable safety profile.
Similar efficacy and safety of dolutegravir between age groups of HIV‐1‐infected paediatric and young adult patients aged 5 years and older
Authors: Frange P , Avettand‐Fenoel V , Veber F , Blanche S 
Published: May 2019

ObjectivesThe aim of the study was to carry out a comparison of the safety and efficacy of dolutegravir‐based regimens among age groups of HIV‐1‐infected paediatric and young adult patients.Patients and methodsThis retrospective monocentric study included 109 patients infected since childhood who began receiving dolutegravir between January 2014 and December 2017. The patients were divided into three groups according to age at the time of dolutegravir initiation: 5–11, 12–17 and 18–25 years old. The primary endpoint was the proportion of patients achieving a plasma viral load (PVL) < 50 HIV‐1 RNA copies/mL within 3 months of dolutegravir initiation (for patients with detectable viraemia at baseline), and maintaining virological suppression (PVL < 50 copies/mL) until the last follow‐up visit (for all patients).ResultsMost of the subjects were antiretroviral‐experienced (91.7%) and virologically suppressed at baseline (66.7%, 54.9% and 56.0% in the 5–11, 12–17 and 18–25 year age groups, respectively). Median follow‐up was 24 months (range 6–54 months). Sustained virological success throughout follow‐up was observed in 79.8% of patients, with similar rates among age groups (87.9%, 72.5% and 84.0%, respectively; P = 0.22). With reinforced measures to improve adherence, undetectable PVL was obtained at the last visit in 88.1% of patients, with similar proportions among age groups (93.9%, 84.3% and 88.0%, respectively; P = 0.51). No emergence of resistance mutations was observed in the 22 patients with virological failure. Dolutegravir was well tolerated; only one patient stopped treatment for severe drug‐related side effects.ConclusionsThe virological efficacy and safety of dolutegravir were similar among the three age groups. Because of its high genetic barrier to resistance, dolutegravir could be especially useful in the paediatric population, in which the risk of poor treatment adherence is high.
Impact of fluorodeoxyglucose uptake on positron emission tomography/computed tomography on chemosensitivity and survival in patients with metastatic urothelial carcinoma
Authors: Kobayashi Masaki , Tanaka Hajime , Tateishi Ukihide , Numao Noboru , Yonese Junji , Ito Masaya , Koga Fumitaka , Fukushima Hiroshi , Uehara Sho , Yoshida Soichiro , Yokoyama Minato , Ishioka Junichiro , Matsuoka Yoh , Saito Kazutaka , Kihara Kazunori , Fujii Yasuhisa 
Published: May 2019

ObjectivesTo evaluate the impact of fluorodeoxyglucose uptake on positron emission tomography/computed tomography on chemosensitivity and survival in patients with metastatic urothelial carcinoma.MethodsThe present study assessed 51 metastatic urothelial carcinoma patients undergoing fluorodeoxyglucose positron emission tomography/computed tomography before first‐line systemic chemotherapy. Fluorodeoxyglucose uptake in metastases was evaluated using the maximum standardized uptake value, which was measured for all eligible lesions, and the highest value among the maximum standardized uptake value measurements in each case was defined as the highest maximum standardized uptake value. The associations between the highest maximum standardized uptake value and objective response rate to chemotherapy, progression‐free survival or cancer‐specific survival were analyzed. For cancer‐specific survival, the C‐index was compared between multivariate models that incorporated predictors in the Bajorin model including the Karnofsky performance status and the presence of visceral metastasis, and the Apolo model additionally including hemoglobin and albumin levels, with/without the highest maximum standardized uptake value.ResultsThe median age was 69 years. The Karnofsky performance status was ≥80% for all patients. Visceral metastasis was observed in 12 patients (24%). The objective response rate, median progression‐free survival and median cancer‐specific survival were 61%, 9 and 26 months in the entire cohort, respectively. The higher highest maximum standardized uptake value was significantly associated with a lower objective response rate, shorter progression‐free survival and shorter cancer‐specific survival (P = 0.01, <0.001 and 0.004, respectively). On multivariate analyses, the highest maximum standardized uptake value was an independent predictor for all end‐points. In the multivariate models for cancer‐specific survival, the C‐index improved from 0.559 to 0.601 and from 0.604 to 0.652 by adding the highest maximum standardized uptake value to the parameter set of the Bajorin model and Apolo model, respectively.ConclusionsHigher fluorodeoxyglucose uptake in metastases was significantly and independently associated with poor chemosensitivity and worse survival outcomes. Fluorodeoxyglucose positron emission tomography/computed tomography might aid in patient counseling and treatment decisions for metastatic urothelial carcinoma patients.
Beyond memory T cells: mechanisms of protective immunity to tuberculosis infection
Authors: Steigler Pia , Verrall Ayesha J , Kirman Joanna R 
Published: May 2019

AbstractTuberculosis (TB) is a serious infectious disease caused by infection with Mycobacterium tuberculosis, and kills more people annually than any other single infectious agent. Although a vaccine is available, it is only moderately effective and an improved vaccine is urgently needed. The ability to develop a more effective vaccine has been thwarted by a lack of understanding of the mechanism of vaccine‐induced immune protection. Over recent decades, many novel TB vaccines have been developed and almost all have aimed to generate memory CD4 T cells. In this review, we critically evaluate evidence in the literature that supports the contention that memory CD4 T cells are the prime mediators of vaccine‐induced protection against TB. Because of the lack of robust evidence supporting memory CD4 T cells in this role, the potential for B‐cell antibody and “trained” innate cells as alternative mediators of protective immunity is explored.
Barriers to recovery‐focused care within therapeutic relationships in nursing: Attitudes and perceptions
Authors: Harris Barbara , Panozzo Gina 
Published: May 2019

AbstractThere are numerous barriers to the therapeutic relationship between nurses and persons with schizophrenia, such as time constraints, communication issues and the requirements of practice policies. The main point of this paper is that the nature of these barriers is such that the nurse may not conceptualize these as barriers or be aware of how his or her responses to these can further entrench existing barriers to relationship or create new ones. If the nurse is not aware of how he or she responds to time pressure, frustration or lack of clarity of practice policy and address this, there is a risk that the patient may perceive the nurse's actions as lacking in care, presence or involvement. As consumers increasingly embrace recovery approaches to mental health that prioritize therapeutic activities within the context of collaborative relationship, psychiatric nurses, with a long tradition of therapeutic relationship, can rise to meet them. It is suggested here that this can only occur if nurses are fully aware of barriers to relationship, their responses to these and the impact of these on relationship with patients. Suggestions for educational and empirical work to further raise awareness and promote understanding of this process are provided.
Computational comparisons of different formulations for the Stackelberg minimum spanning tree game
Authors: Labbé Martine , Pozo Miguel A. , Puerto Justo 
Published: May 2019

AbstractLet be a given graph whose edge set is partitioned into a set R of red edges and a set B of blue edges, and assume that red edges are weighted and contain a spanning tree of G. Then, the Stackelberg minimum spanning tree game (StackMST) is that of pricing (i.e., weighting) the blue edges in such a way that the total weight of the blue edges selected in a minimum spanning tree of the resulting graph is maximized. In this paper, we present different new mathematical programming formulations for the StackMST based on the properties of the minimum spanning tree problem and the bilevel optimization. We establish a theoretical and empirical comparison between these new formulations that are able to solve random instances of 20–70 nodes. We also test our models on instances in the literature, outperforming previous results.
Friends and Allies: LGBT+ Inclusion in Statistics and Data Science
Authors: Thornton Suzanne , Green Brittany , Benn Emma 
Published: May 2019

Abstract
At a conference last year, Suzanne Thornton, Brittany Green and Emma Benn organised a panel session to share advice and recommendations for making the statistics and data science community more inclusive and supportive of gender non-conforming and LGBTQ persons. Here they summarise their discussion in the hope of continuing the conversation
Memory retention of appetitive and aversive conditioning in the damselfish Stegastes fuscus
Authors: Silveira Mayara M. , Ferreira de Souza Jéssica , Pires Moreira Ana L. , Silva Priscila F. , Luchiari Ana C. 
Published: May 2019

AbstractWe compared the memory of damselfish Stegastes fuscus in an aversive and appetitive conditioning task. Fish were trained to associate the sides of the tank that corresponded to the presence of a positive (conspecific presence) or negative (electroshock) stimulus. After two conditioning sessions, they were tested for learning. The fish conditioned to the stimulus were then re‐tested for memory retention after 5, 10 or 15 days. Both the positive and negative rewards were associated with a specific side of the tank, indicating learning ability. Additionally, in both contexts, S. fuscus stored the information learned and showed similar behavioural patterns after 5, 10 and 15 days, suggesting long‐lasting memory. For the ecological context, long lasting memories of social encounters outcomes and negative experiences of threatening situations may confer advantages that ultimately affect fishes’ fitness.
Presence and genetic variability of Piscine orthoreovirus genotype 1 (PRV‐1) in wild salmonids in Northern Europe and North Atlantic Ocean
Authors: Vendramin Niccoló , Cuenca Argelia , Sørensen Juliane , Alencar Anna L. F. , Christiansen Debes H. , Jacobsen Jan A. , Axen Charlotte , Lieffrig François , Ruane Neil M. , Martin Patrick , Sheehan Timothy , Iburg Tine M. , Rimstad Espen , Olesen Niels J. 
Published: May 2019

AbstractPiscine orthoreovirus genotype 1 (PRV‐1) is widespread in farmed Atlantic salmon (Salmo salar L.) populations in northern Europe, Canada and Chile. PRV‐1 occurs in wild fish in Norway and Canada; however, little information of its geographical distribution in wild populations is currently available, and the effect of PRV‐1 infection in wild populations is currently unknown. In this study, we present the findings of a survey conducted on 1,130 wild salmonids sampled in Denmark, Sweden, Ireland, Faroe Islands, France, Belgium and Greenland between 2008 and 2017. PRV‐1 is reported for the first time in wild salmonids in Denmark, Sweden, Faroe Island and Ireland. The annual PRV‐1 prevalence ranged from 0% in France, Belgium and Greenland to 43% in Faroe Islands. In total, 66 samples tested positive for PRV‐1, including Atlantic salmon broodfish returning to spawn and Atlantic salmon collected at the feeding ground north of Faroe Islands. The phylogenetic analysis of S1 sequences of the PRV‐1 isolates obtained in this survey did not show systematic geographical distribution. This study sheds light on the spread and genetic diversity of the virus identified in populations of free‐living fish and provides rationale for screening wild broodfish used in restocking programmes.
Landscape genomics of an obligate mutualism: Concordant and discordant population structures between the leafcutter antAtta texanaand its two main fungal symbiont types
Authors: Smith Chad C. , Weber Jesse N. , Mikheyev Alexander S. , Roces Flavio , Bollazzi Martin , Kellner Katrin , Seal Jon N. , Mueller Ulrich G. 
Published: May 2019

AbstractTo explore landscape genomics at the range limit of an obligate mutualism, we use genotyping‐by‐sequencing (ddRADseq) to quantify population structure and the effect of host–symbiont interactions between the northernmost fungus‐farming leafcutter antAtta texanaand its two main types of cultivated fungus. Genome‐wide differentiation between ants associated with either of the two fungal types is of the same order of magnitude as differentiation associated with temperature and precipitation across the ant's entire range, suggesting that specific ant–fungus genome–genome combinations may have been favoured by selection. For the ant hosts, we found a broad cline of genetic structure across the range, and a reduction of genetic diversity along the axis of range expansion towards the range margin. This population‐genetic structure was concordant between the ants and one cultivar type (M‐fungi, concordant clines) but discordant for the other cultivar type (T‐fungi). Discordance in population‐genetic structures between ant hosts and a fungal symbiont is surprising because the ant farmers codisperse with their vertically transmitted fungal symbionts. Discordance implies that (a) the fungi disperse also through between‐nest horizontal transfer or other unknown mechanisms, and (b) genetic drift and gene flow can differ in magnitude between each partner and between different ant–fungus combinations. Together, these findings imply that variation in the strength of drift and gene flow experienced by each mutualistic partner affects adaptation to environmental stress at the range margin, and genome–genome interactions between host and symbiont influence adaptive genetic differentiation of the host during range evolution in this obligate mutualism.
Seed and pollen dispersal distances in two African legume timber trees and their reproductive potential under selective logging
Authors: Hardy Olivier J. , Delaide Boris , Hainaut Hélène , Gillet Jean‐François , Gillet Pauline , Kaymak Esra , Vankerckhove Nina , Duminil Jérôme , Doucet Jean‐Louis 
Published: May 2019

AbstractThe natural regeneration of tree species depends on seed and pollen dispersal. To assess whether limited dispersal could be critical for the sustainability of selective logging practices, we performed parentage analyses in two Central African legume canopy species displaying contrasted floral and fruit traits: Distemonanthus benthamianus and Erythrophleum suaveolens. We also developed new tools linking forward dispersal kernels with backward migration rates to better characterize long‐distance dispersal. Much longer pollen dispersal in D. benthamianus (mean distance dp = 700 m, mp = 52% immigration rate in 6 km2 plot, s = 7% selfing rate) than in E. suaveolens (dp = 294 m, mp = 22% in 2 km2 plot, s = 20%) might reflect different insect pollinators. At a local scale, secondary seed dispersal by vertebrates led to larger seed dispersal distances in the barochorous E. suaveolens (ds = 175 m) than in the wind‐dispersed D. benthamianus (ds = 71 m). Yet, seed dispersal appeared much more fat‐tailed in the latter species (15%–25% seeds dispersing >500 m), putatively due to storm winds (papery pods). The reproductive success was correlated to trunk diameter in E. suaveolens and crown dominance in D. benthamianus. Contrary to D. benthamianus, E. suaveolens underwent significant assortative mating, increasing further the already high inbreeding of its juveniles due to selfing, which seems offset by strong inbreeding depression. To achieve sustainable exploitation, seed and pollen dispersal distances did not appear limiting, but the natural regeneration of E. suaveolens might become insufficient if all trees above the minimum legal cutting diameter were exploited. This highlights the importance of assessing the diameter structure of reproductive trees for logged species.
World Workshop on Oral Medicine VII: Immunobiologics for salivary gland disease in Sjögren's syndrome: A systematic review
Authors: Gueiros Luiz A. , France Katherine , Posey Rachael , Mays Jacqueline W. , Carey Barbara , Sollecito Thomas P. , Setterfield Jane , Woo Sook Bin , Culton Donna , Payne Aimee S. , Lodi Giovanni , Greenberg Martin S. , De Rossi Scott 
Published: May 2019

AbstractObjectiveThis systematic review evaluated the efficacy of immunobiologics for the management of oral disease in Sjögren's syndrome (SS).Materials and MethodsMEDLINE®, Embase, Scopus, and the Cochrane Library were searched for evidence on the use of immunobiologics for management of glandular disease in SS. Primary outcomes were xerostomia and salivary gland dysfunction, assessed via visual analogue scales, disease‐specific scales for SS, measurement of salivary flow, ultrasound data, and quality of life measures.ResultsSeventeen studies (11 randomized controlled trials and 6 observational studies) met inclusion criteria. Rituximab showed efficacy in improving salivary gland function but not xerostomia. Abatacept showed promise in improving both xerostomia and salivary flow. Belimumab exhibited long‐term improvement of salivary flow and subjective measures. The novel agent CFZ533 improved both disease activity and patient‐reported indexes.ConclusionsThere is strong evidence pointing to the efficacy of rituximab in the management of oral disease in SS. Future controlled trials may elucidate the efficacy of belimumab and abatacept. The new drug CFZ533 is a promising alternative for the management of SS and its salivary gland involvement. In considering these agents, the promise of efficacy must be balanced against the harmful effects associated with biologic agents.
World Workshop on Oral Medicine VII: Targeting the microbiome for oral medicine specialists—Part 1. A methodological guide
Authors: Varoni Elena M. , Bavarian Roxanne , Robledo‐Sierra Jairo , Porat Ben‐Amy Dalit , Wade William G. , Paster Bruce , Kerr Alexander R. , Peterson Douglas E. , Frandsen Lau Ellen 
Published: May 2019

AbstractAdvances in high‐throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven‐step “recipe” for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high‐throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients.
World Workshop on Oral Medicine VII: Clinical evidence of differential expression of lncRNAs in oral squamous cell carcinoma: A scoping review
Authors: Pentenero Monica , Bowers Leah M. , Jayasinghe Ruwan , Yap Tami , Cheong Sok Ching , Kerr Alexander R. , Farah Camile S. , Alevizos Ilias 
Published: May 2019

AbstractBackgroundLong non‐coding RNAs (lncRNAs) have important roles in regulating gene expression pertaining to cell proliferation, survival, migration and genomic stability. Dysregulated expression of lncRNAs is implicated in cancer initiation, progression and metastasis.ObjectivesTo explore, map and summarize the extent of evidence from clinical studies investigating the differential expression of lncRNAs in oral/tongue squamous cell carcinoma.MethodsPubMed, Scopus and Web of Science were used as search engines. Clinical, full‐length, English language studies were included. PRISMA‐ScR protocol was used to evaluate and present results. The present scoping review summarizes relationships of the differential expression of lncRNAs with the presence of tumour and with clinicopathological features including survival.ResultsAlmost half of the investigated transcripts have been explored in more than one study, yet not always with consistent results. The collected data were also compared to the limited studies investigating oral epithelial dysplasia. Data are not easily comparable, first because of different methods used to define what differential expression is, and second because only a limited number of studies performed multivariate analyses to identify clinicopathological features associated with the differentially expressed lncRNAs.ConclusionsStandard methods and more appropriate data analyses are needed in order to achieve reliable results from future studies.