bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined effect of a farnesoid X receptor agonist and dipeptidyl peptidase‐4 inhibitor on hepatic fibrosis
Authors: Shimozato Naotaka , Namisaki Tadashi , Kaji Kosuke , Kitade Mitsuteru , Okura Yasushi , Sato Shinya , Moriya Kei , Seki Kenichiro , Kawaratani Hideto , Takaya Hiroaki , Sawada Yasuhiko , Saikawa Soichiro , Nakanishi Keisuke , Furukawa Masanori , Fujinaga Yukihisa , Kubo Takuya , Asada Kiyoshi , Kitagawa Koh , Tsuji Yuki , Kaya Daisuke , Ozutsumi Takahiro , Akahane Takemi , Mitoro Akira , Yoshiji Hitoshi
Published: June 2019

Aim

Non‐alcoholic steatohepatitis (NASH) has a broad clinicopathological spectrum (inflammation to severe fibrosis). The farnesoid X receptor agonist obeticholic acid (OCA) ameliorates the histological features of NASH; satisfactory antifibrotic effects have not yet been reported. Here, we investigated the combined effects of OCA + a dipeptidyl peptidase‐4 inhibitor (sitagliptin) on hepatic fibrogenesis in a rat model of NASH.

Methods

Fifty Fischer 344 rats were fed a choline‐deficient L‐amino‐acid‐defined (CDAA) diet for 12 weeks. The in vitro and in vivo effects of OCA + sitagliptin were assessed along with hepatic fibrogenesis, lipopolysaccharide–Toll‐like receptor 4 (TLR4) regulatory cascade and intestinal barrier function. Direct inhibitory effects of OCA + sitagliptin on activated hepatic stellate cells (Ac‐HSCs) were assessed in vitro.

Results

Treatment with OCA + sitagliptin potentially inhibited hepatic fibrogenesis along with Ac‐HSC proliferation and hepatic transforming growth factor (TGF)‐β1, α1(I)‐procollagen, and tissue inhibitor of metalloproteinase‐1 (TIMP‐1) mRNA expression and hydroxyproline levels. Obeticholic acid inhibited hepatic TLR4 expression and increased hepatic matrix metalloproteinase‐2 expression. Obeticholic acid decreased intestinal permeability by ameliorating CDAA diet‐induced zonula occludens‐1 disruption, whereas sitagliptin directly inhibited Ac‐HSC proliferation. The in vitro suppressive effects of OCA + sitagliptin on TGF‐β1 and α1(I)‐procollagen mRNA expression and p38 phosphorylation in Ac‐HSCs were almost consistent. Sitagliptin directly inhibited the regulation of Ac‐HSC.

Conclusions

Treatment with OCA + sitagliptin synergistically affected hepatic fibrogenesis by counteracting endotoxemia induced by intestinal barrier dysfunction and suppressing Ac‐HSC proliferation. Thus, OCA + sitagliptin could be a promising therapeutic strategy for NASH.
Weighted gene coexpression network analysis reveals hub genes involved in cholangiocarcinoma progression and prognosis
Authors: Tian Aiping , Pu Ke , Li Boxuan , Li Min , Liu Xiaoguang , Gao Liping , Mao Xiaorong
Published: June 2019

Aim

Cholangiocarcinoma (CCA) is a highly malignant tumor found in the bile duct epithelial cells, and the second most common primary tumor of the liver. However, the pivotal roles of molecular biomarkers in oncogenesis of CCA are unclear. Therefore, we aim to explore the underlying mechanisms of progression and screen for novel prognostic biomarkers and treatment targets.

Method

The data of mRNA sequencing and clinical information of CCA patients in The Cancer Genome Atlas was analyzed by weighted gene coexpression network analysis (WGCNA). Modules and clinical traits were constructed according to Pearson's correlation analysis, and Gene Ontology and pathway enrichment analysis were applied. Hub genes of these modules were screened by intramodule analysis; Cytoscape with Search Tool for the Retrieval of Interacting Genes was utilized to visualize protein–protein interaction of these modules; hub genes of these modules were validated afterwards. Furthermore, the significance of these genes was confirmed by survival analysis.

Results

Genes MRPS18A, CST1, and SCP2 were identified as candidate genes in the module, which was associated with clinical traits including pathological stage, histological grade, and liver function and which also affected overall survival of CCA patients. Nineteen hub genes were analyzed together and were associated with progression and prognosis of CCA. Survival analyses found that several of the multiple genes could serve as biomarkers to stratify CCA patients into low‐ and high‐risk groups.

Conclusion

These candidate genes could be involved in progression of CCA, which could serve as novel prognostic markers and treatment targets. Moreover, most of them were first reported in CCA and deserve further research.
Interventions to improve participation in health‐care decisions in non‐Western countries: A systematic review and narrative synthesis
Authors: Dolan Hankiz , Li Mu , Trevena Lyndal
Published: June 2019

Background

Patients' participation in medical decision making is an important aspect of patient‐centred care. However, there is often uncertainty about its applicability and feasibility in non‐Western countries.

Objective

To provide an overview and assessment of interventions that aimed to improve patients' participation in decision making in non‐Western countries.

Method

Ovid Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, Ovid MEDLINE(R) Epub Ahead of Print, In‐Process, Other Non‐Indexed Citations, without Revisions and Daily Update and Database of Abstracts of Reviews of Effects, were searched from respective inception to February 2018. Studies were included if they (a) were randomized controlled trials, before‐and‐after studies and interrupted time series studies; (b) were conducted in non‐Western countries; (c) aimed to improve patients' participation in dyadic decision making; and (d) reported outcomes relevant to patient participation in decision making. Studies were excluded if they included children, were about triadic decision making or solely focused on information provision without reporting outcomes related to patient participation. Narrative synthesis method was used for data analysis and presentation.

Results

A total of 17 studies, 6 RCTs and 11 non‐RCTs, were included across ten countries. Intervention strategies included patient and/or provider communication skills training, decision aids and a question prompt material. Whilst most of the studies reported increased patient participation, those interventions which had provider or patient training in communication skills were found to be more effective.

Conclusion

Interventions to improve patient participation, within the context of dyadic decision making, in non‐Western countries can be feasible and effective if communication skills training is provided for health‐care providers and/or patients.
Mechanical hysteresis and damage evolution in C/SiC composites under fatigue loading at room and elevated temperatures
Authors: Li Longbiao , Reynaud Pascal , Fantozzi Gilbert
Published: June 2019

In this paper, the mechanical hysteresis and damage evolution in C/SiC ceramic matrix composites (CMCs) under cyclic tension‐tension fatigue loading at room and elevated temperatures in air and in inert atmosphere and different loading frequencies are investigated. The fatigue hysteresis loops models considering multiple matrix cracking modes are developed to establish the relationships between fatigue hysteresis loops, fatigue hysteresis dissipated energy, and fiber/matrix interface shear stress. The evolution of fatigue hysteresis dissipated energy and interface shear stress vs applied cycles is analyzed. It was found that the interface shear stress degradation rate increases with fatigue peak stress, and loading frequency from 40 to 375 Hz.
HLA‐DQB1*02 allele in children with celiac disease: Potential usefulness for screening strategies
Authors: Poddighe Dimitri , Capittini Cristina , Gaviglio Ivan , Brambilla Ilaria , Marseglia Gian Luigi
Published: June 2019

Through a retrospective analysis of a real‐life cohort of children with celiac disease (CD), who underwent HLA‐DQ genotyping, we supported our previous findings indicating the presence of HLA‐DQB1*02 allele in at least 90%–95% of pediatric patients. In the present study, reporting the HLA‐DQ analysis from 184 children (age range: 1–16 years) diagnosed with CD in a single centre, we found that 97.29% of all these CD children (n = 179 out of 184 genotyped patients) resulted to be carriers of at least one copy of HLA‐DQB1*02 allele. If a widened screening for CD should result to be appropriate in the pediatric population after further clinical research, this observation might be potentially exploited to consider a two‐step screening strategy, starting with the HLA‐DQB1*02 targeted analysis followed by the specific serology for CD in these predisposed patients only. However, additional and larger studies are needed to support our findings.
Skin bacterial microflora of two closely related mountain newts (Salamandridae) – the Yellow‐spotted mountain newt Neurergus derjugini and the Kaiser's mountain newt Neurergus kaiseri – in the wild and in a breeding facility highlight new conservation perspectives
Authors: Vaissi S. , Sharifi M. , Hernandez A. , Nikpey S. , Taran M.
Published: June 2019

Microbiome research is important for the identification of factors that are associated with the ex situ care of amphibians, such as potential contagious and lethal pathogens. Nevertheless, it can be also used to establish whether newts can adapt to exposure to new microbial communities, which would be important for the success of future reintroductions into the natural habitat. There is no available information regarding the skin flora naturally occurring in mountain newts of the genus Neurergus, including the Yellow‐spotted mountain newt Neurergus derjugini and the Kaiser's mountain newt Neurergus kaiseri. In this study, skin bacterial microbiota of wild adults and individuals of both species from a captive‐breeding facility (CBF) were compared. Four bacteria that naturally occur on the skin of wild adult N. derjugini were identified (Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Escherichia coli). Six bacteria were positively detected on the skin of wild adult N. kaiseri [S. aureus, B. subtilis, B. cereus, E. coli, Rhodococcus equi, Klebsiella (Enterobacter) aerogenes]. Our results indicate that the skin microbiota of F1 offspring (≤ 2 months of age) from the CBF did not correspond exactly to the microbial community identified in wild adult N. derjugini. However, ≥ 75% of the bacteria found in older individuals (≥ 1 year of age) living at the CBF over the long term corresponded to those of their wild counterparts. It would appear that post‐metamorphic and adults of both species might be better able to resist and adapt to natural microbiota than larvae.
Transforming Feedback: An Application Framework for Group Feedback Videos in Design
Authors: Brown Kylie , Fridman Ilya
Published: June 2019

This article presents the development and application of group feedback videos (GFVs) in design education. A case study shows how visually‐rich GFVs were developed in a practice‐based design studio subject where learners were required to work in teams and independently calibrate an ability to form judgements on the qualities of their own work. Breaking away from traditional models of individual written feedback, students were instead provided with holistic reviews of project outcomes in a GFV format. Assessment examples were presented from across the cohort with the goal of encouraging open discussion and self‐reflection on studio practice. GFVs supported learning processes through three key characteristics: information richness, group learning and sharing, and formative engagement. What differentiated this approach from previous studies was the focus on audio‐visual group delivery to enhance feedback's richness. By replicating an in‐class group critique session, GFVs allowed commonly summative assessment stages to be seen as formative. This study contributes to existing literature through an application framework that may be used by design educators who are seeking to implement GFV methods within their own studio teaching practice.
Discovering floristic and geoecological gradients across Amazonia
Authors: Tuomisto Hanna , Van doninck Jasper , Ruokolainen Kalle , Moulatlet Gabriel M. , Figueiredo Fernando O. G. , Sirén Anders , Cárdenas Glenda , Lehtonen Samuli , Zuquim Gabriela
Published: June 2019

Aim

To map and interpret floristic and geoecological patterns across the Amazon basin by combining extensive field data with basin‐wide Landsat imagery and climatic data.

Location

Amazonia.

Taxon

Ground truth data on ferns and lycophytes; remote sensing results reflect forest canopy properties.

Methods

We used field plot data to assess main ecological gradients across Amazonia and to relate floristic ordination axes to soil base cation concentration, Climatologies at High Resolution for the Earth's Land Surface Areas (CHELSA) climatic variables and reflectance values from a basin‐wide Landsat image composite with generalized linear models. Ordination axes were then predicted across all Amazonia using Landsat and CHELSA, and a regional subdivision was obtained using k‐medoid classification.

Results

The primary floristic gradient was strongly related to base cation concentration in the soil, and the secondary gradient to climatic variables. The Landsat image composite revealed a tapestry of broad‐scale variation in canopy reflectance characteristics across Amazonia. Ordination axis scores predicted using Landsat and CHELSA variables produced spatial patterns consistent with existing knowledge on soils, geology and vegetation, but also suggested new floristic patterns. The clearest dichotomy was between central Amazonia and the peripheral areas, and the available data supported a classification into at least eight subregions.

Main conclusions

Landsat data are capable of predicting soil‐related species compositional patterns of understorey ferns and lycophytes across the Amazon basin with surprisingly high accuracy. Although the exact floristic relationships may differ among plant groups, the observed ecological gradients must be relevant for other plants as well, since surface reflectance recorded by satellites is mostly influenced by the tree canopy. This opens exciting prospects for species distribution modelling, conservation planning, and biogeographical and ecological studies on Amazonian biota. Our maps provide a preliminary geoecological subdivision of Amazonia that can now be tested and refined using field data of other plant groups and from hitherto unsampled areas.
Latitudinal effects of anthropogenic factors driving raptor species richness across the American continent
Authors: Chapa‐Vargas Leonardo , Ceballos Gerardo , Tinajero Romeo , Torres‐Romero Erik Joaquín
Published: June 2019

Aim

Geographic gradients in species richness have been traditionally attributed to variation in environmental conditions. However, untangling the importance of human activities in explaining spatial patterns in raptor species richness, still remains a challenge. We evaluated the relative importance of how human impacts and ecogeographical conditions shape the latitudinal patterns of resident (n = 140) and migratory (n = 35) raptor species richness in the American continent, and analysed whether these factors differ between the Nearctic and the Neotropical regions.

Location

American Continent.

Taxon

Raptor species.

Methods

We processed BirdLife distributional data for 175 raptor species distributed in America, and a set of three ecogeographical and three human impact variables at a spatial resolution of 96.5 × 96.5 km. We applied simple, multiple, simultaneous auto‐regressive models and partial regression analyses to explore the associations between ecogeographical conditions and human impacts on raptor richness.

Results

At the continental scale and the Neotropical region, global forest structure is the main driver of richness patterns for all raptors combined, and for resident and migratory species alone. In the Nearctic region, human accessibility was the best explanatory variable to understand the spatial patterns of richness regardless of the raptor group analysed.

Main conclusions

Environmental features play a leading role in determining raptor species richness. However, the independent contribution of human activities emerges as an important factor in explaining richness patterns of migratory species at the continental scale and within the Neotropical region, whereas humans become particularly important in the Nearctic region for all raptors, residents and migratory species. We show for the first time how human‐related factors influence raptor species richness.
Knockdown of STIL suppresses the progression of gastric cancer by down‐regulating the IGF‐1/PI3K/AKT pathway
Authors: Wang Ju , Zhang Yong , Dou Zhongxia , Jiang Hongwei , Wang Yongqiang , Gao Xiaoping , Xin Xiangyang
Published: June 2019

SCL/TAL1 interrupting locus (STIL) regulates the mitotic centrosome to promote the centriolar replication and cell cycling, and is associated with malignancies. However, the role and mechanism of STIL in gastric cancer (GC) remain elusive. STIL expression in GC tissue microarray was detected by immunohistochemistry (IHC). GC cells were transduced with control lentivirus or lentivirus for expression STIL‐specific shRNA and the effect of STIL silencing on the malignant behaviors of GC cells was measured in vitro and in vivo. The potential mechanisms underlying the action of STIL were analyzed by transcriptome microarray and bioinformatics. STIL expression was up‐regulated in GC tissues both in our cohort and the data from the cancer genome atlas, and positively associated with T stage and poor overall survival of GC patients. Knockdown of STIL significantly inhibited the proliferation and clonogenicity of human GC cells and attenuated the growth of implanted GC in vivo. Furthermore, STIL silencing induced cell cycle arrest in G2/M phase and apoptosis of GC cells. Transcriptome analysis indicated that STIL silencing modulated many gene expression, particularly for down‐regulating the IGF‐1/PI3K/AKT pathway. In addition, treatment with SC79, an AKT activator, significantly mitigated the effect of STIL‐silencing in GC cells. In conclusion, STIL promotes gastric carcinogenesis and progression by enhancing the IGF‐1/PI3K/AKT signaling, and STIL may be a novel target for intervention of GC.
For Whom the Bell Trolls: Shifting Troll Behaviour in the Twitter Brexit Debate
Authors: Llewellyn Clare , Cram Laura , Hill Robin L. , Favero Adrian
Published: June 2019

In 2017 Twitter released a list of 2,752 accounts believed to be connected to state‐sponsored Russian operative manipulation of the 2016 American Election. We investigate the behaviour of these accounts in the UK–EU referendum using our own unique longitudinal Twitter dataset. We identify Brexit‐related content from 419 of these accounts, totalling 3,485 tweets between 29 August 2015 and 3 October 2017. While these accounts were primarily designed to resemble American citizens, accounts created in 2016 contained German and Italian locations and terms in user profiles, suggesting targeting of wider international electoral processes. Brexit was one of many targets, likely indicating coordinated repurposing of ‘troll’ activity over time. We analyze behavioural shifts in account behaviour in relation to external events, introducing a temporal dimension not typical of political Twitter studies. The ‘troll’ account behaviour altered radically on UK–EU referendum day, shifting from generalized disruptive tweeting to retweeting other troll accounts to amplify their effect.
Female patients are less satisfied with biological treatment for psoriasis and experience more side‐effects than male patients: results from the prospective BioCAPTURE registry
Authors: van der Schoot L.S. , van den Reek J.M.P.A. , Groenewoud J.M.M. , Otero M.E. , Njoo M.D. , Ossenkoppele P.M. , Mommers J.M. , Koetsier M.I.A. , Berends M.A.M. , Arnold W.P. , Peters B. , Andriessen M.P.M. , Den Hengst C.W. , Kuijpers A.L.A. , de Jong E.M.G.J.
Published: June 2019

Background

Female sex has been reported as a predictor for treatment discontinuation with biological therapies for psoriasis, although reasons remain unclear. It can be hypothesized that lower satisfaction with biological treatment in women might add to the lower drug survival rates.

Objectives

To identify possible differences in satisfaction with biological treatment between female and male patients using the Treatment Satisfaction Questionnaire for Medication (TSQM).

Methods

Data of psoriasis patients treated with biologics were obtained from the prospective, multicentre, daily‐practice BioCAPTURE registry. Longitudinal TSQM data were analysed by linear mixed models. Relevant patient characteristics were incorporated as possible confounding factors. Post hoc analysis of adverse events was performed in order to investigate differences between sexes.

Results

We included 315 patients with 396 corresponding treatment episodes (137 adalimumab, 90 etanercept, 137 ustekinumab, 24 secukinumab and 8 infliximab). Almost forty per cent of the patients were female. Women had significantly lower baseline PASI scores (P = 0.01). Longitudinal analyses demonstrated lower TSQM scores for ‘side‐effects’ (P = 0.05) and ‘global satisfaction’ (P = 0.01) in female patients compared with male patients over 1 year of treatment. Women reported more relevant adverse events in the context of biologic treatment compared to men (rate ratio 1.79; P < 0.001), with more fungal (rate ratio 2.20; P = 0.001) and herpes simplex infections (rate ratio 3.25; P = 0.005).

Conclusions

This study provides a prospective, longitudinal analysis of treatment satisfaction with biologics in female and male patients with psoriasis. Women were slightly less satisfied with treatment regarding side‐effects and global satisfaction. Differences in treatment satisfaction and side‐effects might add to the fact that women discontinue biological treatments more often.
Behavioural changes during the parr–smolt transformation in coho salmon Oncorhynchus kisutch: is it better to be cool?
Authors: Elsner Rick A. , Shrimpton J. Mark
Published: June 2019

Behavioural changes that occur during the parr–smolt transformation were investigated in juvenile coho salmon Oncorhynchus kisutch. Fish from two populations were examined from the Fraser River catchment in British Columbia, Canada; a short and a long‐distance migrating population. Fish showed a significant decrease in condition factor and significant increase in gill Na+K+‐ATPase activity during the spring indicating that they became competent smolts, but no difference between populations. Temperature preference trials were conducted using a shuttlebox system throughout the spring. Mean temperature preference did not differ between the two populations, but preferred temperature decreased with development from 16.5 ± 0.3°C for parr to 15.5 ± 0.4°C for smolts. Mean swimming velocity was also greater in smolts than parr, but there was no difference between the two populations. The preference for warmer water temperature observed for parr in early spring may be advantageous for stimulating smolt development. Preference for slightly cooler temperatures observed for smolts would sustain elevated seawater tolerance during the smolt window by a short time and may ensure successful transition to the marine environment.
Hyaluronan synthesis supports glutamate transporter activity
Authors: Hayashi Mariko Kato , Nishioka Tomoki , Shimizu Hideo , Takahashi Kanako , Kakegawa Wataru , Mikami Tetsuri , Hirayama Yuri , Koizumi Schuichi , Yoshida Sachiko , Yuzaki Michisuke , Tammi Markku , Sekino Yuko , Kaibuchi Kozo , Shigemoto‐Mogami Yukari , Yasui Masato , Sato Kaoru
Published: June 2019

Hyaluronan is synthesized, secreted, and anchored by hyaluronan synthases (HAS) at the plasma membrane and comprises the backbone of perineuronal nets around neuronal soma and dendrites. However, the molecular targets of hyaluronan to regulate synaptic transmission in the central nervous system have not been fully identified. Here, we report that hyaluronan is a negative regulator of excitatory signals. At excitatory synapses, glutamate is removed by glutamate transporters to turn off the signal and prevent excitotoxicity. Hyaluronan synthesized by HAS supports the activity of glial glutamate transporter 1 (GLT1). GLT1 also retracted from cellular processes of cultured astrocytes after hyaluronidase treatment and hyaluronan synthesis inhibition. A serial knockout study showed that all three HAS subtypes recruit GLT1 to cellular processes. Furthermore, hyaluronidase treatment activated neurons in a dissociated rat hippocampal culture and caused neuronal damage due to excitotoxicity. Our findings reveal that hyaluronan helps to turn off excitatory signals by supporting glutamate clearance.

image

Cover Image for this issue: doi: 10.1111/jnc.14516.
Co‐inhibition of BET proteins and PD‐L1 as a potential therapy for OSCC through synergistic inhibition of FOXM1 and PD‐L1 expressions
Authors: Wang Wei , Tan Junyan
Published: June 2019

Background

Bromodomain and extra‐terminal domain (BET) proteins are important epigenetic regulators that facilitate the transcription of genes in chromatin areas linked to acetylated histones. JQ1, a BET inhibitor (BETi), has anti‐proliferative and apoptosis activity against many cancers including oral squamous cell carcinoma (OSCC). In this research, we investigated the mechanism underlying the effects of JQ1 in OSCC and investigated strategies to increase its therapeutic potential.

Methods

The OSCC Cal27 and SCC25 cell lines were used for in vitro experiments. Cells were treated with JQ1 and/or siRNA targeting PD‐L1 (siPD‐L1), and cell viability, apoptosis, and cell cycle were evaluated by cell proliferation assay, colony formation assay, apoptosis, and cell cycle analysis. Levels of cleaved caspase‐3, p53, BRD4, PD‐L1, and FOXM1 were determined by quantitative real‐time PCR and Western blot. The effects of single inhibitor or combination inhibitor treatment on tumors derived from Cal27 cells in mice were monitored.

Results

FOXM1 and PD‐L1 were downregulated by JQ‐1 in a dose‐dependent manner. Combined JQ1 and siPD‐L1 treatment synergistically inhibited cell growth and induced apoptosis and cell cycle arrest in vitro and synergistically inhibited tumor growth in vivo compared with single treatments. The combination treatment also synergistically suppressed FOXM1 and PD‐L1 signaling pathways in OSCC cells.

Conclusion

Our research suggests that FOXM1 and PD‐L1 are targets of BETi in OSCC cells and indicate that combining PD‐L1 blockade with BETi may be a useful therapeutic approach in OSCC through further suppressing FOXM1 and PD‐L1.
The economic burden of oral squamous cell carcinoma in Australia
Authors: Pollaers Katherine , Massingham Ian , Friedland Peter L. , Farah Camile S.
Published: June 2019

Objectives

The financial burden of treatment for oral squamous cell carcinoma in Australia has never been reported, and there is a paucity of international data. Here, we report the direct costs of treatment of surgically resectable oral cancer in a tertiary public hospital in Australia over a 15‐year period.

Materials and Methods

Pathology department records, records of hospital attendance and hospital finance department records were interrogated to determine the direct costs of inpatient and outpatient treatment. Costs were adjusted using the total health price index so that all costs were equivalent to costings for the 2016/2017 financial year.

Results

A total of 113 cases were identified as suitable for inclusion. Complete inpatient and outpatient hospital attendance and costing data for treatment and subsequent 2‐year follow‐up was available for 29 cases. The average total cost over the 2‐year period was $92 958AUD (median $102 722, range $11 662‐$181 512). On average, 92.8% of costs were incurred in the first year post‐diagnosis. Inpatient costs, outpatient costs and total costs increased with increasing pathological cancer stage. Both 1‐ and 2‐year post‐diagnosis overall cost for patients with Stage 4 oral cavity cancer were more than two times greater than for patients with Stage 1 oral cancer.

Conclusion

It is well documented that patients diagnosed at an earlier stage will have better survival outcomes, and it is assumed that the economic burden of their treatment will be less. We have shown that there is a direct correlation between cancer stage and cancer treatment cost. The findings provide clear economic support for oral cancer screening initiatives to detect earlier stage cancers, and the need to investigate novel techniques and technologies to detect oral squamous cell carcinoma early and reduce recurrence and mortality rates.
The Role of Curiosity in the Sociopolitical Development of Black and Latinx Adolescents
Authors: Clark Shelby , Seider Scott
Published: June 2019

Sociopolitical development, the process of coming to understand and take action against systems of oppression, is associated with key outcomes for youth. Although rooted in Paulo Freire's work on critical consciousness, sociopolitical development models overlook a motivational attribute—curiosity—that Freire characterized as a catalyst of such development. This longitudinal study investigated the relationship between curiosity and two aspects of sociopolitical development (social analysis, societal involvement) in a sample of Black and Latinx adolescents (N = 659). Longitudinal growth models demonstrated positive growth in all constructs over 4‐years of high school. Multivariate growth models revealed a positive correlation at baseline between curiosity and both constructs; growth in curiosity was also positively correlated with growth in social analysis and societal involvement.
Efficacy and safety of telbivudine and tenofovir disoproxil fumarate in preventing hepatitis B vertical transmission: A real‐life practice
Authors: Liu Jinfeng , Wang Jing , Yan Taotao , Du Dan , Qi Caijing , Cao Furong , Yao Naijuan , Yang Yuan , He Yingli , Tian Zhen , Ren Danfeng , Zhu Li , Chen Tianyan , Zhao Yingren
Published: June 2019

Mother‐to‐child transmission (MTCT) is a major obstacle in the elimination of hepatitis B virus (HBV) infection. Telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) are the two most common antiviral medicines for preventing MTCT. However, the efficacy and safety of LdT and TDF in preventing HBV vertical transmission during the second to third trimester have not been compared rigorously. Therefore, we carried out a prospective multicentre cohort study of chronic hepatitis B in mothers with HBV DNA > 106 IU/mL, receiving LdT or TDF during the second to third trimester. Among the 893 mothers enrolled, 857 (LdT/TDF/untreated group (NTx) = 396/325/136) completed consecutive follow‐up with 854 infants (LdT/TDF/NTx = 395/323/136). LdT and TDF treatment resulted in a similar decrease of HBV DNA in mothers at delivery. Multivariate analysis indicated that only HBsAg titre at the baseline correlated with viral DNA decrease (P = 0.015). With intention‐to‐treat analysis, MTCT rates in the LdT, TDF and NTx group were 4.41%, 2.42% and 22.08%, respectively. An increasing vertical transmission rate was found to be closely associated with higher HBsAg titre, 5.32% and 17.65% infection rate was estimated in infants born to mothers with HBsAg > 4 and >5 log10 IU/mL, respectively. No serious side effects were reported in either mothers or infants. LdT and TDF treatments were well tolerated and showed comparable efficacy in reducing MTCT. Higher risk of MTCT was shown in pregnant women with HBsAg > 4 log10IU/mL.
SLC10A1 S267F variant influences susceptibility to HBV infection and reduces cholesterol level by impairing bile acid uptake
Authors: Cheng Xiang , Wang Ying , Tian Jianbo , Zhou Li , Chen Xueqin , Guo Hui , Zeng Junchao , Shen Na , Li Jiaoyuan , Ke Juntao , Zhu Ying , Gong Jing , Chang Jiang , Liu Li , Zhong Rong
Published: June 2019

The SLC10A1 Ser267Phe (S267F) variant has been reported to severely inhibit hepatitis B virus (HBV) infection and taurocholate transport activity. This study aimed to clarify the effects of this variant on HBV infection and bile acid metabolism. SLC10A1 S267F was genotyped in 2907 HBV‐exposed subjects (including HBV persistent carriers and spontaneously recovered subjects) and 1364 unexposed subjects (HBV marker‐negative subjects), followed by replication I, comprising 914 exposed subjects and 1123 unexposed subjects, and replication II, comprising 355 children born to HBsAg‐positive mothers (226 HBV‐infected children and 129 controls). Intriguingly, SLC10A1 AA was observed only in the unexposed group, but not in the exposed group. The SLC10A1 A allele consistently decreased HBV infection risk compared with the G allele (OR = 0.76, 95% CI: 0.64‐0.90 in combined samples). In addition, children with the SLC10A1 GA genotype had a reduced risk of perinatal transmission (OR = 0.31, 95% CI: 0.14‐0.71). Moreover, unexposed subjects with the SLC10A1 AA genotype exhibited decreased serum total cholesterol and low‐density lipoprotein cholesterol compared to those with the GG or GA genotypes (P = 2.975 × 10−4 and 0.004, respectively). The study highlighted the role of the SLC10A1 S267F variant in the loss of the ability to support HBV infection and taurocholate transport activity. Subjects with the AA genotype may escape from HBV infection and present decreased cholesterol levels as a consequence of impaired bile acid uptake.
M‐SAKHI—Mobile health solutions to help community providers promote maternal and infant nutrition and health using a community‐based cluster randomized controlled trial in rural India: A study protocol
Authors: Patel Archana B. , Kuhite Priyanka N. , Alam Ashraful , Pusdekar Yamini , Puranik Amrita , Khan Samreen Sadaf , Kelly Patrick , Muthayya Sumithra , Laba Tracey‐Lea , Almeida Michelle D' , Dibley Michael J.
Published: June 2019

Reduction of childhood stunting is difficult to achieve by interventions that focus only on improving nutrition during infancy. Comprehensive interventions that extend through the continuum of care from pregnancy to infancy are needed. Mobile phones are now successfully being used for behaviour change communication to improve health. We present the methodology of an mHealth intervention “Mobile Solutions Aiding Knowledge for Health Improvement” (M‐SAKHI) to be delivered by rural community health workers or Accredited Social Health Activists (ASHAs) for rural women, below or up to 20 weeks of pregnancy through delivery until their infant is 12 months of age. This protocol paper describes the cluster randomized controlled trial to evaluate the effectiveness of M‐SAKHI. The primary objective of the trial is to reduce the prevalence of stunting (height‐for‐age < −2z‐score) in children at 18 months of age by 8% in the intervention as compared with control. The secondary objectives include evaluating the impact on maternal dietary diversity, birth weight, infant and young child feeding practices, infant development, and child morbidity, along with a range of intermediate outcomes for maternal, neonatal, and infant health. A total of 297 ASHAs, five trained counsellors, and 2,501 participants from 244 villages are participating in this study. The outcome data are being collected by 51 field research officers. This study will provide evidence regarding the efficacy of M‐SAKHI to reduce stunting in young children in rural India, and if effective, the cost‐effectiveness of M‐SAKHI.
Tropical rainforest flies carrying pathogens form stable associations with social nonhuman primates
Authors: Gogarten Jan F. , Düx Ariane , Mubemba Benjamin , Pléh Kamilla , Hoffmann Constanze , Mielke Alexander , Müller‐Tiburtius Jonathan , Sachse Andreas , Wittig Roman M. , Calvignac‐Spencer Sébastien , Leendertz Fabian H.
Published: June 2019

Living in groups provides benefits but also incurs costs such as attracting disease vectors. For example, synanthropic flies associate with human settlements, and higher fly densities increase pathogen transmission. We investigated whether such associations also exist in highly mobile nonhuman primate (NHP) Groups. We studied flies in a group of wild sooty mangabeys (Cercocebus atys atys) and three communities of wild chimpanzees (Pan troglodytes verus) in Taï National Park, Côte d'Ivoire. We observed markedly higher fly densities within both mangabey and chimpanzee groups. Using a mark–recapture experiment, we showed that flies stayed with the sooty mangabey group for up to 12 days and for up to 1.3 km. We also tested mangabey‐associated flies for pathogens infecting mangabeys in this ecosystem,Bacillus cereusbiovaranthracis(Bcbva), causing sylvatic anthrax, andTreponema pallidum pertenue, causing yaws. Flies contained treponemal (6/103) andBcbva(7/103) DNA. We culturedBcbvafrom all PCR‐positive flies, confirming bacterial viability and suggesting that this bacterium might be transmitted and disseminated by flies. Whole genome sequences ofBcbvaisolates revealed a diversity ofBcbva, probably derived from several sources. We conclude that flies actively track mangabeys and carry infectious bacterial pathogens; these associations represent an understudied cost of sociality and potentially expose many social animals to a diversity of pathogens.
A unified framework for plant life‐history strategies shaped by fire and herbivory
Authors: Archibald Sally , Hempson Gareth P. , Lehmann Caroline
Published: June 2019

Fire and herbivory both remove aboveground biomass. Environmental factors determine the type and intensity of these consumers globally, but the traits of plants can also alter their propensity to burn and the degree to which they are eaten. To understand plant life‐history strategies associated with fire and herbivory we need to describe both response and effect functional traits, and how they sort within communities, along resource gradients, and across evolutionary timescales. Fire and herbivore functional traits are generally considered separately, but there are advances made in understanding fire that relate to herbivory, and vice versa. Moreover, fire and herbivory interact: the presence of one consumer affects the type and intensity of the other. Here, we present a unifying conceptual framework to understand plant strategies that enable tolerance and persistence to fire and herbivory. Using grasses as an example, we discuss how flammability and fire tolerance, palatability, and grazing tolerance traits might organize themselves in ecosystems exposed to these consumers, and how these traits might have evolved with reference to other strong selective processes, like aridity. Our framework can be used to predict both the diversity of life‐history strategies and plant species diversity under different consumer regimes.
The auditory‐verbal hallucinations of Welsh–English bilingual people
Authors: Hadden Lowri M. , Alderson‐Day Ben , Jackson Mike , Fernyhough Charles , Bentall Richard P.
Published: June 2019

Objectives

Psychological models of voice‐hearing propose that auditory‐verbal hallucinations occur when inner speech is attributed to a source external to the self. Approximately half of the world's population is multilingual, and the extent to which they use a second language for inner speech depends on their experience and competency in it. Bilingualism therefore provides a natural window into the processes operating in auditory‐verbal hallucinations, but no systematic study of voice‐hearing in bilinguals has hitherto been conducted.

Design

A mixed‐methods observational study of psychiatric service users who hear voices and who are Welsh–English bilingual.

Methods

Thirty‐seven participants were interviewed about their history and use of Welsh and English and divided into three groups: those who learnt Welsh first (L1 Welsh), those who learnt English first (L1 English), and those who learnt the two languages simultaneously. Detailed phenomenological data were collected using The Mental Health Research Institute Unusual Perceptions Schedule.

Results

Both qualitative and quantitative data indicated very considerable variation in the extent to which voices were in Welsh, English, or both, with some voice‐hearers reporting that the predominant language of their voices had changed with time. There were modest but statistically significant associations between the predominant language of voices and age of language acquisition (late Welsh learners did not hear voices in Welsh), frequency of language use (more frequent use of Welsh was associated with more Welsh voices), and subjective language proficiency (proficiency in English was associated with a tendency to hear English voices).

Conclusions

Although this was a small study, it was the first of its kind. There is a need for more research on the implications of bilingualism for psychosis in particular and mental illness more generally. The results are broadly consistent with the hypothesis that hallucinated voices are misattributed inner speech.

Practitioner points

Assessments of people with mental health difficulties should routinely inquire whether they are multilingual and, if so, which language they prefer to use.

People with mental health difficulties may have difficulty expressing complex issues and emotions in a second language, despite apparent fluency.

When working with bilingual people who hear voices, mental health professionals should consider the language used by the voices when conducting assessments and proposing formulations.
Successful management of pediatric oral pemphigus vulgaris with topical corticosteroid monotherapy
Authors: Le Michelle , Ghazawi Feras M. , Miedzybrodzki Barbara , Chauvin Peter J. , Jafarian Fatemeh
Published: June 2019

Pemphigus vulgaris (PV) is an autoimmune intraepithelial bullous disease that affects the skin and mucous membranes. Typically, the management of PV is challenging, with systemic corticosteroids being the mainstay of treatment. We describe the case of a 14‐year‐old girl who was diagnosed with oral PV and successfully treated with topical corticosteroids alone. This case details a pediatric mucosal PV case successfully managed solely with topical corticosteroids.
Ophiostomatales associated with wounds on hardwood trees in Poland
Authors: Jankowiak R. , Bilański P. , Ostafińska A. , Linnakoski R.
Published: June 2019

Wounds on trees provide entrance for many members of the Ophiostomatales (Ascomycota), including economically damaging tree pathogens. Because very little is known regarding wound‐associated fungi on hardwoods in Europe or their potential nitidulid beetle vectors (Coleoptera), the aim of this survey was to explore the diversity of these fungi in Poland. Wound samples associated with 26 tree species were collected from 18 stands in Poland. Fungi belonging to the Ophiostomatales were isolated and identified based on morphology and DNA sequence comparisons of five gene regions, combined with phylogenetic analyses. In total, 32 taxa were identified, including 20 known and 12 currently undescribed species. In addition, Grosmannia cainii, Ophiostoma cf. ponderosae, O. sparsiannulatum and Sporothrix aurorae were reported for the first time outside of the USA. The wound‐associated members of the Ophiostomatales recovered from hardwoods showed high diversity and specificity. Among the species recovered, 16 belonged to Sporothrix, 11 represented Ophiostoma s. l., five could be assigned to Leptographium s. l., and one Graphilbum species was detected. Among the studied tree species, wounds on Quercus robur appeared to be the most vulnerable to infection by members of the Ophiostomatales. All the nitidulid beetle species were found in association with species assignable to Ophiostoma and Sporothrix. This study detected a significant association between the occurrence of species belonging to the Ophiostomatales and the health status of the wounded trees. Some of the isolated species were host specific although Ophiostoma quercus, the most frequently encountered species, had a broad host range.
Validation of a portable device (iSperm®) for the assessment of stallion sperm motility and concentration
Authors: Dini Pouya , Troch Lucas , Lemahieu Isabel , Deblende Peter , Daels Peter
Published: June 2019

The objective of this study was to evaluate the accuracy of a novel, portable device (iSperm® Equine for assessing concentration and motility of stallion semen). In the first experiment, semen concentration was determined by the iSperm® Equine (Aidmics Biotechnology), Androvision® (Minitube) and NucleoCounter® SP‐100™ (ChemoMetec). The total motility and progressive motility were determined by the iSperm® Equine and the Androvision® using the manufacturer's guidelines. Frozen/thawed semen samples (n = 33) at various dilutions were analysed for concentration and motility with the above‐mentioned devices. There was a significant correlation between the concentrations measured with iSperm® and NucleoCounter® at all the measured dilutions. Moreover, <10% difference in concentrations was observed between the iSperm® and NucleoCounter® using the Bland–Altman test. There was also a significant correlation between iSperm® and Androvision® for total and progressive motility. In the second experiment, the parameters used in the Androvision® were modified to match those of the iSperm®. Total motility and progressive motility of frozen/thawed semen samples (n = 10) were determined, and the similarity between the Androvision® and iSperm® was confirmed by correlation studies and Bland–Altman test. The results of these experiments demonstrate that the iSperm® offers a reliable and practical alternative for the semi‐automated measurement of concentration and motility of stallion semen in the field. The iSperm® enables the practitioner to obtain objective and repeatable measurements on a variety of semen types (fresh, cooled and frozen) in the field at the time of insemination and thus acquire more insight into the quantity and quality of the provided insemination doses. This mare‐side diagnostic tool may help practitioners in identifying presumed subfertility problems more rapidly and act accordingly.
Towards uniformity in the definition of acceptable mismatches for highly sensitized patients
Authors: Chen Mian , Zoet Yvonne , Roelen Dave , Martorell Jaume , Middleton Derek , Slavcev Antonij , Iniotaki Aliki , Claas Frans , Fuggle Susan
Published: June 2019

The Eurotransplant (The Eurotransplant International Foundation) acceptable mismatch programme has been shown to be a successful tool to enhance transplantation of highly sensitized patients(HSPs). However, patients with rare HLA phenotypes in relation to the Eurotransplant donor population remain on the waiting list. EUROSTAM is an European Union funded project to explore the feasibility of a Europe‐wide acceptable mismatch programme enabling transplantation of HSPs with rare HLA phenotypes within their own organ exchange organization. The present study, which forms part of the EUROSTAM project, assesses the differences in the practices of the laboratories in different countries with respect to their HLA antibody profiling and risk adverseness. In the serum exchange exercises of 18 samples, a high level of variability has been shown in both assays and interpretation of results. In the data exchange exercise when all participants were given the same Luminex raw data for analysis, a high degree of consensus was reached where the median fluorescent intensity values of beads were <500 and >2000 for standard single antigen bead assays, or <500 and >5000 for assignment of acceptable mismatches. The risk adverseness analysis has showed distinct patterns of attitudes towards the perceived risks based on HLA antibody assay results, most probably influenced by the local protocols of the clinical transplant programme of each laboratory. In order to ensure fairness and maintain consistencies of organ exchange among partner transplant centres, a centralized facility will be instrumental for a uniform definition of acceptable mismatches.