bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic significance of BRAF mutation alone and in combination with microsatellite instability in stage III colon cancer
Authors: Chouhan Hanumant , Sammour Tarik , L. Thomas Michelle , W. Moore James
Published: November 2018

Purpose

The prognostic significance of biomarkers in colorectal cancer is still being defined. This study aimed to determine the prognostic significance of BRAF mutation alone and in combination with microsatellite instability (MSI), in stage III colon cancer.

Methods

Curatively resected stage III colon cancers were studied from a 33‐year period. Clinicopathological data were collated (adjuvant chemotherapy, age, gender, obstruction, perforation, tumour location, grade, presence of mucin, nodal stage, extramural vascular, and perineural invasion). MSI status was established and molecular testing for BRAF (V600E) was performed. Four mutation categories were examined: “traditional” (microsatellite stable [MSS]/BRAF −ve), “presumed Lynch” (MSI/BRAF −ve), “sporadic MSI” (MSI/BRAF +ve), and “other BRAF” (MSS/BRAF +ve). These factors were correlated with cancer‐specific survival.

Results

In total, 686 unselected cases met our inclusion criteria, of which 15.7% had a BRAF mutation and 13.8% showed MSI. In the adjusted analysis, neither BRAF mutation nor MSI mutation were independently prognostic. On univariate analysis, survival in presumed Lynch cancers was similar to traditional cancers (5‐year survival: 62% and 61%, respectively). While there was no difference in cancer‐specific survival between sporadic MSI and other BRAF, both these tumour group had poorer outcome when compared to traditional or presumed Lynch cancers. Adjusted analysis of the four groups, however, showed that none of the subgroups were independently prognostic.

Conclusion

BRAF‐mutated cancers demonstrated a trend toward poorer outcomes, however, when adjusted for clinicopathological factors and chemotherapy, BRAF mutation was not found to be an independent prognostic biomarker in stage III colon cancer, even when combined with MSI.
Biomechanical efficacy of contact lens‐assisted collagen cross‐linking in porcine eyes
Authors: Wollensak Gregor , Spörl Eberhard , Herbst Hermann
Published: November 2018

Purpose

Contact lens‐assisted corneal cross‐linking (CACXL) has been proposed for the cross‐linking treatment in thin corneas. The aim of this study was to assess the biomechanical efficacy of this treatment.

Methods

Post‐mortem porcine eyes were treated with standard cross‐linking and with cross‐linking placing a contact lens soaked with isoosmolar riboflavin solution on the debrided cornea with or without an adherent precorneal riboflavin film of up to 100 μm thickness. Three soft contact lenses (Air Optix Aqua, SofLens and Galifa) with different degrees of hydrophilic properties were tested. After cross‐linking with a surface UVA irradiance of 3 mW/cm² for 30 min (fluence 5.4 J/cm²), a 400 μm deep anterior corneal flap was created using a lamellar rotating microkeratome. Biomechanical stress–strain measurements and thermal shrinkage tests were performed.

Results

In the Air Optix Aqua group (30% hydration) without riboflavin film, Young′s modulus and stress at 8% strain were increased significantly versus untreated controls and the effect was 92.4% respectively 86.35% of the standard CXL value. In the SofLens group (59% hydration) without riboflavin film, Young′s modulus and stress at 8% strain were increased significantly versus untreated controls and the effect was 67.04% respectively 65.28% of the standard CXL value. In the Galifa group (72% hydration) without riboflavin film, Young′s modulus and stress at 8% strain were increased significantly versus untreated controls and the effect was about 68.48% respectively 75.52% of the standard CXL value. In all samples with a precorneal riboflavin film under the contact lens, there was no significant biomechanical effect compared to the untreated controls. Similarly, in the hydrothermal experiments at 70°C, there was a typical mushroom pattern with increased resistance to thermal shrinkage in the anterior stroma after standard CXL, a markedly reduced mushroom effect using a riboflavin‐soaked contact lens only and no effect with the use of a riboflavin‐soaked contact lens plus a precorneal riboflavin film.

Conclusion

The biomechanical effect of CACXL in porcine corneas is about one‐third less than after standard CXL. The efficacy of CACXL might be improved by reducing or omitting the riboflavin film on the contact lens. Further risk assessment studies are necessary.
Three years of vegetation development worth 30 years of secondary succession in urban‐industrial grassland restoration
Authors: Kövendi‐Jakó Anna , Halassy Melinda , Csecserits Anikó , Hülber Karl , Szitár Katalin , Wrbka Thomas , Török Katalin
Published: November 2018

Questions

The restoration of unused urban‐industrial areas has largely been neglected despite their great potential for nature conservation purposes. We applied three plant introduction treatments at a highly degraded industrial area to test whether plant material introduced onto industrial areas initiates plant assemblages similar in composition to those of reference grasslands. We specifically asked (a) Does restoration differ between primary and secondary reference sites in terms of overall species richness and cover three years after the introduction of plant material? (b) What is the sociability of species of the vegetation resulting from different treatments?

Location

Restoration and reference grassland sites with acidic sandy soil in the temperate region of the EU, NE Hungary, Nyírség.

Methods

As restoration techniques, we (a) directly seeded a single dominant species, (b) applied a commercial seed mixture, and (c) transferred hay. We compared species composition, cover, species richness and sociability of species in restoration treatments to reference grasslands. Inventories of vascular plant species were made at five randomly placed 2 m × 2 m sampling units per plot.

Results

The species composition of seeded restoration plots (with a single dominant species and a commercial seed mixture) became similar to that of reference grasslands. Both types of seeding resulted in a similar cover, whereas seeding a commercial seed mixture and hay transfer resulted in a species richness similar to that of reference grasslands. The cover of the natural constituents (NC) of seeded plots also reached that of reference grasslands, while hay addition resulted in a lower cover and a higher number of NC than other methods.

Conclusions

The introduction of propagules in degraded industrial areas can provide communities similar, after three years, to those of secondary reference grasslands that are 30 years of age. We conclude that investing in the restoration of native grasslands at unused urban‐industrial sites can be a great opportunity to enhance biodiversity.
Self‐poisoning with 60 tablets of Apixaban, a pharmacokinetics case report
Authors: Franck Bénédicte , Dulaurent Sylvain , El Balkhi Souleiman , Monchaud Caroline , Picard Nicolas , Couderc Sylvain , Marquet Pierre , Saint‐Marcoux Franck , Woillard Jean‐Baptiste
Published: November 2018

A 67‐year‐old man was admitted to the emergency department about 5 h after deliberate self‐poisoning with 300 mg of Apixaban. The clinical examination did not show any organ dysfunctions or haemorrhagic signs, and the patient's life was not in danger. The first analysis, upon admission, showed a concentration of 2655 μg l−1 of Apixaban. The Cmax was observed 17 h after the intake (3654 μg l−1), about four times the classical Tmax value (median [range]: 4 h [2–4]). The Apixaban was then eliminated following a first order elimination with a calculated half‐life of 10.8 h. The anti‐Xa activity seems to be linearly related to concentration up to 4000 μg l−1. This report suggests that the use of activated charcoal should be effective up to 17 h after a massive intake.
Effectiveness and safety of 110 or 150 mg dabigatran vs. vitamin K antagonists in nonvalvular atrial fibrillation
Authors: Blin Patrick , Dureau‐Pournin Caroline , Cottin Yves , Bénichou Jacques , Mismetti Patrick , Abouelfath Abdelilah , Lassalle Regis , Droz Cécile , Moore Nicholas
Published: November 2018

Aims

We compared the 1‐year safety and effectiveness of dabigatran 110 mg (D110) or 150 mg (D150) twice daily to vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation.

Methods

New user cohort study of patients dispensed D110 or D150 vs. VKA in 2013 for nonvalvular atrial fibrillation, followed 1 year in the French Système National des Données de Santé (66 million persons). D110 and D150 users were matched 1:1 with VKA users on sex, age, date of first drug dispensing and high‐dimensional propensity score. Hazard ratios [HR (95% confidence intervals)] for stroke and systemic embolism (SSE), major bleeding (MB) and death were computed using Cox proportional hazards or Fine and Gray models during exposure.

Results

In 14 442 matched D110 and VKA patients, mean age 79, 49% male, 91% with CHA2DS2‐VASc ≥2 and 8% with HAS‐BLED score >3, incidence rates of SSE were 1.9% and 2.6% person‐years [HR 0.69 (0.56–0.84)], MB 1.8% and 2.9% [0.62 (0.51–0.76)], death 7.2% and 8.6% [0.84 (0.76–0.94)]. In 8389 matched D150 and VKA patients, mean age 67, 67% male, 65% with CHA2DS2‐VASC ≥2; < 5% HAS‐BLED >3, incidence rates were for SSE 1.4% and 1.9% [0.76 (0.56–1.04)], MB 0.6% and 1.9% [0.30 (0.20–0.46)], death 1.6% and 3.6% [0.46 (0.35–0.59)]. Numbers needed to treat to observe one fewer death were 78 for D110, 88 for D150.

Conclusion

In real life D110 and D150 were at least as effective, and safer than VKA.
Weight gain as a predictor of frontal and temporal lobe volume loss in bipolar disorder: A prospectiveMRIstudy
Authors: Bond David J , Su Wayne , Honer William G , Dhanoa Taj , Batres‐y‐Carr Tegan , Lee Susanne S , Torres Ivan J , Lam Raymond W , Yatham Lakshmi N
Published: November 2018

Objectives

A sizable fraction of people with bipolar I disorder (BDI) experience a deteriorating clinical course with increasingly frequent mood episodes and chronic disability. This is believed to result from neurobiological illness progression, or neuroprogression. Excessive weight gain predicts neuroprogression across multiple brain illnesses, but no prospective studies have investigated this inBDI. The objective of this study was to determine whetherBDIpatients who experienced clinically significant weight gain (CSWG; gaining ≥7% of baseline weight) over 12 months had greater 12‐month brain volume loss in frontal and temporal regions important toBDI.

Methods

In 55 early‐stageBDIpatients we measured (i) rates ofCSWG, (ii) the number of days with mood symptoms, usingNIMHLifeCharts, and (iii) baseline and 12‐month brain volumes, using 3TMRI. We quantified brain volumes using the longitudinal processing stream in FreeSurfer v6.0. We used general linear models for repeated measures to investigate whetherCSWGpredicted volume loss, adjusting for potentially confounding clinical and treatment variables.

Results

After correction for multiple comparisons,CSWGin patients predicted greater volume loss in the left orbitofrontal cortex (effect size [ES; Cohen'sd] = −1.01,P = 0.002), left cingulate gyrus (ES = −1.31,P < 0.001), and left middle temporal gyrus (ES = −0.96,P = 0.004). Middle temporal volume loss predicted more days with depression (β = −0.406,P = 0.010).

Conclusions

These are the first prospective data on weight gain and neuroprogression inBDI.CSWGpredicted neuroprogression, and neuroprogression predicted a worse clinical illness course. Trials of weight loss interventions are needed to confirm the causal direction of the weight gain‐neuroprogression relationship, and to determine whether weight loss is a disease‐modifying treatment.
Should I trust you? Autistic traits predict reduced appearance‐based trust decisions
Authors: Hooper Jasmine J. , Sutherland Clare A. M. , Ewing Louise , Langdon Robyn , Caruana Nathan , Connaughton Emily , Williams Nikolas , Greenwell‐Barnden Jayden , Rhodes Gillian
Published: November 2018

Facial impressions of trustworthiness guide social decisions in the general population, as shown by financial lending in economic Trust Games. As an exception, autistic boys fail to use facial impressions to guide trust decisions, despite forming typical facial trustworthiness impressions (Autism, 19, 2015a, 1002). Here, we tested whether this dissociation between forming and using facial impressions of trustworthiness extends to neurotypical men with high levels of autistic traits. Forty‐six Caucasian men completed a multi‐turn Trust Game, a facial trustworthiness impressions task, the Autism‐Spectrum Quotient, and two Theory of Mind tasks. As hypothesized, participants’ levels of autistic traits had no observed effect on the impressions formed, but negatively predicted the use of those impressions in trust decisions. Thus, the dissociation between forming and using facial impressions of trustworthiness extends to the broader autism phenotype. More broadly, our results identify autistic traits as an important source of individual variation in the use of facial impressions to guide behaviour. Interestingly, failure to use these impressions could potentially represent rational behaviour, given their limited validity.
Autoantibodies to killer cell immunoglobulin-like receptor 3DL1 in patients with systemic lupus erythematosus
Authors: Doi A , Kano S , Asano M , Takahashi Y , Mimori T , Mimori A , Kaneko H
Published: November 2018

A genetic variant of the killer immunoglobulin-like receptor 3DL1 (KIR3DL1) has been found in patients with systemic lupus erythematosus (SLE). Herein, we investigated the presence of autoantibodies to KIR3DL1 in a cohort of patients with SLE. We tested sera from 28 patients with SLE, 11 patients with rheumatoid arthritis (RA) and 17 healthy control subjects for anti-KIR3DL1 activity by an enzyme-linked immunosorbent assay (ELISA) using recombinant KIR3DL1-enhanced green fluorescent protein (EGFP) and EGFP proteins. Anti-KIR3DL1 antibodies were detected in 22 (79%) of the 28 patients with SLE, whereas they were present in only three (27%) of the 11 patients with RA examined. Notably, 10 (91%) of the 11 samples from patients with SLE prior to therapy had anti-KIR3DL1 antibodies. None of the samples from healthy donors were positive for the antibodies. Here, we report the presence of anti-KIR3DL1 antibodies in the sera of patients with SLE for the first time. Anti-KIR3DL1 autoantibodies may be involved in the pathogenesis of autoimmune diseases.
Inflammation in osteoarthritis: is it time to dampen the alarm(in) in this debilitating disease?
Authors: van den Bosch M H J
Published: November 2018

Osteoarthritis (OA) is the most common joint disease that strongly reduces the quality of life in patients; However, no disease-modifying therapy is available. For a long time, OA was considered a non-inflammatory disease that was the result of ‘wear-and-tear’ and abnormal mechanics, and therefore many considered the term ‘osteoarthritis’ a misnomer. However, during the last decades the notion arose that inflammation is not only present in the majority of OA patients but, rather, actively involved in the progression of the disease. Influx of immune cells is observed in the synovium and a plethora of inflammatory mediators is present in tissues and fluids from OA patients. These mediators cause the production of degrading enzymes that break down the cartilage matrix, which is the main hallmark of OA. Alarmins, which belong to the group of danger signals, have been implicated in many inflammatory diseases. They are among the first factors to be released upon cell stress due to, for example, infection, damage and inflammation. They attract and activate cells of the immune system and therefore lie at the base of the inflammatory reaction. In this narrative review, an overview of the history of OA, the evolving concept of inflammation as important factor in the OA pathogenesis, and particularly the central role that alarmins play in the initiation and maintenance of the low-grade inflammatory response in OA, is provided. Moreover, the targeting of alarmins as a promising approach to dampen the inflammation in OA is highlighted.
HOW DO MINIMUM WAGE ADJUSTMENTS AFFECT WAGES IN CHINA: EVIDENCE BASED ON ADMINISTRATIVE PERSONAL INCOME TAX DATA
Authors: Peng Langchuan , Wang Xiaxin , He Daixin
Published: November 2018

By using unique administrative personal income tax data covering the population of a middle‐sized Chinese city from 2009 to 2013, we explore how minimum wage adjustments affect wages of low‐wage workers. The empirical evidence documented in this paper suggests a unique pattern of minimum wage regulation: while it permits wages to stay below the prevailing minimum wage threshold temporarily, it does encourage a higher growth rate for wages below the threshold. Overall, such a pattern might help lessen any downward pressures on employment, while ensuring that low‐wage earners gradually get better off over time. (JEL J3, J6, P5)
Intramural schwannoma involving a vein
Authors: Fernandez‐Flores Angel , Saeb‐Lima Marcela , Cassarino David S.
Published: November 2018

Schwannoma involving the blood vessels is a rare phenomenon. So far, only three cases of intravascular schwannoma have been described (all of which were intraluminal), and the origin of the schwannoma in such cases is not yet completely understood. Here, we describe a very rare intramural venous schwannoma in the subcutaneous right prepatellar area of a 31‐year‐old man. The schwannoma grew by enlarging and thickening the blood vessel wall, between two preserved layers of the vein. In some areas, there was erosion of the luminal layer, with fibrin apposed to the tumor. The tumor expressed S100 and was negative for CD31, CD34, desmin, and smooth muscle actin. The expression of p16 was preserved. Endothelial markers such as CD31 and Factor VIII showed the endothelial lining (which was D2‐40‐negative) above the tumor. Although degenerative atypia was present, there were no mitotic figures or necrosis identified.
Implementation of HPV‐based cervical cancer screening in an organised regional screening programme: 3 years of experience
Authors: Veijalainen Olga , Kares Saara , Kujala Paula , Vuento Risto , Osuala Veronika , Tirkkonen Mika , Luukkaala Tiina , Kholová Ivana , Mäenpää Johanna
Published: November 2018

Objective

The aim of this study was to evaluate the performance of human papillomavirus (HPV)‐based screening in the framework of an organised cervical cancer screening programme.

Methods

A total of 46 708 women aged 35‐60 years invited to the regional cervical cancer screening programme from 1 January 2012, to 31 December 2014, were enrolled. Overall, 17 770 women were screened by the Abbot RealTime hrHPV test with cytology triage and 15 605 were screened by conventional (Papanicolaou, Pap) cytology. In both groups, women with at least low‐grade squamous intraepithelial lesions were referred directly for colposcopy, whereas HPV‐positive women with borderline or normal cytology were invited to intensified screening in the following year. In the Pap group, the indication for intensified follow‐up was borderline cytology.

Results

The attendance rate was similar in the HPV and Pap groups (72% and 71%, respectively). Overall, 6.0% of women in the HPV group vs 6.4% in the Pap group were referred to intensified follow‐up (relative risk 0.94, 95% confidence interval [CI]: 0.87‐1.03). At the index screening years, the relative sensitivity of the HPV test with cytology triage vs conventional screening was 1.64 (95% CI: 1.05‐2.55) for CIN2+ and 2.06 (95% CI: 1.17‐3.41) for CIN3+. The specificity of the hrHPV test with cytology triage for CIN2+ and CIN3+ was equal to that of the Pap screening (99.2% vs 99.2% for CIN2+ and 99.1% vs 99.1% for CIN3+).

Conclusions

Due to its high sensitivity and specificity, primary hrHPV testing with cytology triage seems to be acceptable for cervical cancer screening in an organised setting.
Promoting sustainable development through civil society: A case study of the EU’s NSA/LA thematic programme in Kyrgyzstan
Authors: Pierobon Chiara
Published: November 2018

The article focuses on the contribution of the European Union (EU) in promoting sustainable development through the involvement of civil society in partner countries. More specifically, it analyses the main features and outcomes of the projects implemented by civil society organizations (CSOs) in Kyrgyzstan under the EU thematic programme Non‐State Actors and Local Authorities in Development (NSA/LA). Despite its importance—this is the only EU programme providing direct support to non‐state actors and local authorities engaged in poverty reduction—to date, there has been very little research on the functioning of this instrument on the ground. This article seeks to fill this gap in the literature by examining the EU’s contribution to sustainable development through a case study on Kyrgyzstan. The study is based on primary data: 10 semi‐structured interviews conducted with the EU‐funded organizations implementing the NSA/LA programme. The NSA/LA projects were analysed by considering two major fields of engagement of non‐state actors in the development process: as service providers and as advocates (Banks & Hulme, 2012). Overall, the organizations awarded EU support were not only focused on fulfilling short‐term needs but also sought to introduce new ways of dealing with poverty and inequality, positioning themselves between the “Big‐D” and the “little‐d” approaches to development (Bebbington, Hickey, & Mitlin, 2008). Nonetheless, the EU‐funded projects were too limited and fragmented to be able to sustain long‐term structural change. Therefore, the EU should place new emphasis on creating synergies between new and old structures at the grassroots level and establishing mechanisms and bodies that could merge and co‐ordinate their efforts. In addition, the calls for proposals could highlight the need to share the lessons learnt by “obliging” the beneficiaries to act as multipliers and to pass on their positive experience to neighbouring communities. Finally, the EU could stimulate the funded organizations to experiment with innovative mechanisms of involvement in the policy‐making process, by making this aspect a mandatory requirement of the projects implemented with its support.
Increasing therapy‐related myeloid neoplasms in multiple myeloma
Authors: Fernández‐Caballero Mariana , Salmerón Diego , Dolores Chirlaque María , Chen‐Liang Tzu H. , Hurtado Ana M. , García Malo María D. , Ortuño Francisco J. , Roldán Vanessa , Vicente Vicente , Jerez Andrés , De Arriba Felipe
Published: November 2018

Background

Despite the longer survival achieved in multiple myeloma (MM) patients due to new therapy strategies, a concern is emerging regarding an increased risk of secondary primary malignancies (SPMs) and how to characterize those patients at risk. We performed a retrospective study covering a 28‐year follow‐up period (1991‐2018) in a tertiary single institution.

Material and Methods

Data of 403 MM patients were recorded and compared with the epidemiologic register of the population area covered by our centre, calculating the standardize incidence ratio (SIR) for the different types of SPMs diagnosed in the MM cohort. Fine and Gray regression models were used to identify risk factors for SPMs.

Results

Out of the 403 MM patients, 23 (5.7%) developed SPMs: 13 therapy‐related myeloid (TRM) malignancies (10 of them (77%) myelodysplastic syndrome (MDS), 1 acute lymphoid leukaemia and 9 solid neoplasms. In the MM cohort, the relative risk of MDS was significantly higher than in the general population. Survival of patients with TRM malignancies was poor with a median of 4 months from the diagnosis, and most of them showed complex karyotype. Within the MM subset, multivariable analysis showed a higher risk of TRM malignancies in patients that previously received prolonged treatment with lenalidomide (>18 months).

Conclusions

Though the improvement in MM outcome during the last decades is an unprecedented achievement, it has been accompanied by the rise in TRM malignancies with complex cytogenetic profile and poor prognosis that are in the need of an improved biologic and therapeutic approach.
Standing low‐field magnetic resonance imaging as a diagnostic modality for solar keratoma in a horse
Authors: Mageed M. , Elfadl A. , Blum N. , Wegert J. , Kremer F. , Swagemakers J.
Published: November 2018

A 22‐year‐old Friesian gelding was presented with a history of chronic, nonresolving lameness localised to the right front foot. Radiographs showed a smoothly marginated circular lucent area with a rim of increased opacity adjacent to the solar canal of the distal phalanx. The magnetic resonance imaging (MRI) revealed a reversed V‐shaped smoothly demarcated space‐occupying mass causing invagination of the solar laminae towards the solar canal arch and deformity of the adjacent surface of the distal phalanx. The mass was removed surgically and submitted for histopathology, which revealed a keratoma and periosteal fibrosis. Six weeks post‐surgery the horse returned to the previous work level and 8 months follow‐up showed no recurrence of keratoma. This report highlights the usefulness of MRI as a diagnostic modality for solar keratoma.
Melasma: Updates and perspectives
Authors: Kwon Soon‐Hyo , Na Jung‐Im , Choi Ji‐Young , Park Kyoung‐Chan
Published: November 2018

Management of melasma is highly challenging due to inconsistent treatment results and frequent relapses. However, recent studies revealed that melasma may not only be a disease of melanocytes, but also a photoaging skin disorder. Herein, we attempt to validate that melasma is indeed a photoaging disorder by presenting the histopathologic findings of melasma: solar elastosis, altered basement membrane, increased vascularization and increased mast cell count. We also provide some therapeutic implications based on these findings and a discussion on the latest updates and perspectives regarding treatment.
Upregulation of Helicoverpa armigera core RNA interference genes by bacterial infections and its effect on the insect–bacteria interaction
Authors: Baradaran E. , Moharramipour S. , Asgari S. , Mehrabadi M.
Published: November 2018

RNA interference (RNAi) is an extremely conserved defence mechanism. The antiviral role of the RNAi pathway in insects is well documented; however, the relevance of this pathway in other aspects of insect immunity is largely unknown. In this study, we questioned whether RNAi has any function during insect–bacteria interactions. For this, we assessed induction of the RNAi pathway in response to bacterial infections by monitoring the expression of dicer1/argonaute1 and dicer2/argonaute2, which are important genes in the microRNA and short interfering RNA sub‐pathways respectively. Bacterial cells of Bacillus thuringiensis and Serratia marcescens were injected into the haemocoel of fifth‐instar larvae of Helicoverpa armigera, whereas double‐distilled water was injected into control insects. Expression levels of the RNAi‐related genes increased in the bacteria‐injected larvae compared with controls. Transcript knockdown of dicer1 reduced the replication of B. thuringiensis; as a consequence, larval mortality decreased compared with the control. However, replication of S. marcescens increased following dicer1 silencing, which led to higher rates of larval mortality when compared with the control. RNAi of dicer2 promoted replication of both bacteria in the larvae and also enhanced larval mortality. Therefore, dicer1 and dicer2 affected larval survival and the replication rates of the pathogenic bacteria, suggesting their roles in the interactions.
Designing User‐Centered Humanitarian Technologies with Displaced People in Iraq: Lessons from Refunite's Mobile Family Tracing Platform
Authors: Robehmed Sacha
Published: November 2018

As almost all adults in Iraq own a mobile phone, there is great scope to reach and engage with internally displaced persons (IDPs) in Iraq through mobile technologies. This article argues for the importance of a user‐centered design approach when using mobile technologies in humanitarian response. A user‐centered approach considers context and places IDPs’ lived experiences as active technology users at the forefront of project design and implementation. The argument is supported by a case study of Refunite, a family tracing platform that uses mobile technologies to help people find their missing loved ones. This article seeks to address the gap in the literature on user‐centered humanitarian mobile technology projects, particularly in relation to the Middle East. Given the current lack of guidelines on mobile technologies in humanitarian response, the article concludes by recommending that humanitarian practitioners draw on an existing framework, the Principles for Digital Development (2016).
CD147 promotes progression of head and neck squamous cell carcinoma via NF‐kappa B signaling
Authors: Yu Binbin , Zhang Yan , Wu Kailiu , Wang Lizhen , Jiang Yingying , Chen Wantao , Yan Ming
Published: November 2018

CD147/basigin (BSG) is highly upregulated in many types of cancer, our previous study has found that CD147/BSG is highly expressed in head and neck squamous cell carcinoma (HNSCC) stem cells, but its role in HNSCC and the underlying mechanism is still unknown. In this study, we investigated the role of CD147 in the progression of HNSCC. Real‐time PCR, western blot and immunohistochemistry were used to detect the expression of CD147 in total 189 HNSCC tissues in compared with normal tissues. In addition, we used proliferation, colony formation, cell cycle and apoptosis, migration and invasion as well as wound‐healing assay to determine the biological roles of CD147 in HNSCC. Then, a xenograft model was performed to evaluate tumor‐promoting and metastasis‐promoting role of CD147 in HNSCC. The results showed that upregulated CD147 expression was associated with aggressive clinicopathologic features in HNSCC. In addition, CD147 promoted proliferation, migration and reduced the apoptosis phenotype of HNSCC cells in vitro as well as tumor initiation and progression in vivo. Furthermore, we demonstrated that CD147 promoted HNSCC progression through nuclear factor kappa B signaling. Therefore, we concluded that CD147 promoted tumor progression in HNSCC and might be a potential prognostic and treatment biomarker for HNSCC.
Epidermolysis bullosa‐specific module of the Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire
Authors: Chernyshov P.V. , Suru A. , Gedeon I. , Derevyanko L.A. , Tiplica G.S. , Salavastru C.M.
Published: November 2018

Background

Epidermolysis bullosa (EB) may have severe impact on different aspects of patients’ life. Until now there was no EB‐specific quality of life (QoL) instrument for young children.

Objective

To create EB‐specific proxy module of the Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire.

Methods

Focus groups with parents of children with EB were organized. Parents of EB children were interviewed by the project staff with regard to their perception of QoL issues of the skin disease of their children.

Results

Focus groups with parents of EB children in Ukraine and Romania were organized. Parents represented eight boys and 12 girls from 3 months to 4 years old with different EB types and disease severity. Based on the analysis of focus groups’ results, two EB specific items that were not mentioned by parents of children with other skin diseases and therefore were not included to the dermatology‐specific InToDermQoL questionnaire were developed: ‘problems with defecation’ and ‘problems with shoes’. These problems were mentioned by 55% of all parents and 11.76% of parents that represented EB children older than 1 year, respectively.

Conclusion

We want to invite other centres and EB related organizations to join our project starting from the pilot test. There are many different reasons why QoL measurement is important in dermatology clinical practice and our goal is practical use of the instrument in children with EB.
HSPB8 over‐expression prevents disruption of blood–brain barrier by promoting autophagic flux after cerebral ischemia/reperfusion injury
Authors: Li Fazhao , Yang Binbin , Li Ting , Gong Xiyu , Zhou Fangfang , Hu Zhiping
Published: November 2018

Heat‐shock protein B8 (HSPB8) has been recently reported to confer neuroprotection against ischemia/reperfusion (I/R)‐induced cerebral injury in vivo and in vitro. However, the molecular mechanism is still elusive. This study focused on the effect of intracerebroventricular (i.c.v) delivery of lenti‐HSPB8 virus against neurological injury in a rat model of cerebral I/R and explored the underlying mechanism. We found that lentivirus i.c.v injection‐induced HSPB8 over‐expression strongly alleviated infarct volume, improved neurobehavioral outcomes, and reduced brain edema in rat middle cerebral artery occlusion/reperfusion (MCAO/R) model. Concomitantly, HSPB8 over‐expression noticeably prevented blood–brain barrier (BBB) disruption after cerebral I/R injury as indicated by the reduction in Evans blue leakage and IgG detection in the ipsilateral hemisphere compared with the vehicle group. Moreover, immunoblotting and immunofluorescence staining of tight junction proteins claudin‐5 and occludin showed that HSPB8 over‐expression prevented the degradation of these proteins induced by MCAO/R, which indicated the protective effect of HSPB8 on BBB. Western blotting and immunostaining techniques were also utilized to analyze the expression of the markers of autophagy. We found that HSPB8 over‐expression promoted autophagic flux, evidenced by increased ratio of LC3 I/II, accumulation of Beclin‐1 expression and enhanced p62 degradation. i.c.v injection of 15 μg autophagy inhibitor 3‐methyladenine (3‐MA) was applied at the onset of reperfusion. The results showed that 3‐MA elicited a significant loss of the protective effect of HSPB8 against MCAO/R‐induced neurological defect, Evans blue extravasation, and the loss tight junction proteins, suggesting that the BBB protective role of HSPB8 was, at least in part, mediated through autophagy. Collectively, HSPB8 may represent a potential therapeutic agent for preserving BBB integrity following cerebral I/R injury.

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Cover Image for this issue: doi: 10.1111/jnc.14488.
Impact of local endometrial injury on in vitro fertilization/intracytoplasmic sperm injection outcomes: A systematic review and meta‐analysis
Authors: Gui Juan , Xu Wangming , Yang Jing , Feng Ling , Jia Jing
Published: November 2018

Aim

Recent studies have revealed positive effects of endometrial injury on clinical pregnancy rates, but with inconsistent results. The aim of this meta‐analysis was to assess the efficacy of endometrial injury (biopsy and/or hysteroscopy) as a potential treatment measure for implantation failure in the in vitro fertilization population.

Methods

We searched in PubMed for studies comparing the efficacy of endometrial injury versus no intervention in women with at least one implantation failure. A random‐effects model was used to evaluate the clinical pregnancy rate (CPR) and the live birth rate (LBR).

Results

Seventeen studies (11 randomized and 6 non‐randomized studies) were included in this meta‐analysis, including 1864 women in the intervention group and 2193 women in the control group. Overall, the CPR and LBR were significantly higher in the intervention group than in the control group (for CPR, n = 3997, 16 studies, P < 0.00001, risk ratio (RR) = 1.47, 95% confidence interval [CI] [1.24, 1.74]; for LBR, n = 2361, 11 studies, P = 0.003, RR = 1.41, 95% CI [1.12, 1.78]). However, after excluding the non‐randomized studies, there was no significant difference in CPR (P = 0.29 for endometrial biopsy, P = 0.05 for hysteroscopy) and LBR (P = 0.23 for endometrial biopsy, P = 0.39 for hysteroscopy) between the intervention group and the control group.

Conclusion

There is still insufficient evidence to support the use of endometrial injury in women with implantation failure. Robust randomized controlled studies should be designed and performed before clinical implementation of endometrial injury.
Use of Parental Benefits by Family Income in Canada: Two Policy Changes
Authors: Margolis Rachel , Hou Feng , Haan Michael , Holm Anders
Published: November 2018

Objective: This article examines how two recent policy extensions affected the use and sharing of parental benefits in Canada and how this differed by family income.

Background: Paid parental benefits positively affect economic and health outcomes. However, not all policy changes increase leave‐taking, especially among low‐income families.

Method: Drawing on administrative data from 1998 to 2012, we estimate linear probability models to examine the likelihood of either parent using parental benefits and multinomial logit models to examine patterns in sharing benefits. We stratify models by household income to examine how the two policy changes affected families differently across the income spectrum.

Results: Both policies increased use more among low‐income families than those with higher incomes, which is likely due to widening eligibility criteria that affected low‐income families disproportionately. Second, policy design induced different patterns of sharing benefits in response to the two policy changes. In contrast to the 2001 policy that only moderately increased sharing of parental benefits, Quebec's 2006 program explicitly promoted gender equality and increased sharing of benefits across all income groups, but three times as much for middle‐ and high‐income families than low‐income families.

Conclusion: We conclude that policy design shapes socioeconomic inequality in newborns' early life parental context.
Bifactor model of effortful control and impulsivity and their prospective prediction of ego resiliency
Authors: Wang Frances L. , Eisenberg Nancy , Spinrad Tracy L.
Published: November 2018

Objective

Children’s effortful control and impulsivity are important predictors of the personality trait, ego resiliency (i.e., resiliency). Most researchers have not considered the fact that effortful control and impulsivity share substantial conceptual and empirical overlap, yet they also have been shown to be distinct. We tested a bifactor model of effortful control and impulsivity to characterize their shared and unique variance, the prospective prediction of resiliency by the factors of the bifactor model, and moderation by sex and age.

Method

In a longitudinal study of children (N = 214; 76.5% non‐Hispanic Caucasian, 12.2% Hispanic, 11.3% other race/ethnicity), parent‐ and teacher‐reported effortful control and impulsivity, as well as behavioral measures of effortful control, were assessed on two occasions (T1: 4.5–8 years; T2: 6–10 years). Parent‐reported resiliency was used as a covariate (T1) and the outcome (T3: 8–12 years).

Results

The bifactor model yielded a common effortful inhibitory control factor, pure attentional control factor, and pure impulsivity factor. Pure impulsivity and pure attentional control positively predicted resiliency, but only for girls. Effortful inhibitory control did not uniquely predict resiliency.

Conclusion

Disentangling the shared and unique aspects of effortful control and impulsivity could clarify the roles they play in important outcomes, such as resiliency.
Fine‐scale spatial genetic structure in the Minami‐daito Island population of the Ryukyu scops owl Otus elegans
Authors: Sawada A. , Iwasaki T. , Takagi M.
Published: November 2018

Multiple factors can give rise to population genetic structure. Therefore, the generating process of genetic structure should be examined from multiple aspects simultaneously. We describe the fine‐scale genetic structure of the Ryukyu scops owl Otus elegans interpositus population on Minami‐daito Island and test isolation‐by‐distance, isolation‐by‐adaptation and assortative mating as candidates for its underlying mechanisms. Spatial principal component analysis detected a spatial autocorrelation structure for males, but not for females. Discriminant analysis of principal components and STRUCTURE analysis allowed us to classify the owl population into six genetically distinct groups. These clustering results were associated with relatedness. In addition, to these descriptive analyses, analyses of mechanisms preferred isolation‐by‐distance to others. Therefore, we inferred that isolation by distance and kinship structure are the most important underlying processes leading to their genetic structure.
Molecular distribution, 13C‐isotope, and enantiomeric compositions of carbonaceous chondrite monocarboxylic acids
Authors: Aponte José C. , Woodward Hannah K. , Abreu Neyda M. , Elsila Jamie E. , Dworkin Jason P.
Published: November 2018

The water‐soluble organic compounds in carbonaceous chondrite meteorites constitute a record of the synthetic reactions occurring at the birth of the solar system and those taking place during parent body alteration and may have been important for the later origins and development of life on Earth. In this present work, we have developed a novel methodology for the simultaneous analysis of the molecular distribution, compound‐specific δ13C, and enantiomeric compositions of aliphatic monocarboxylic acids (MCA) extracted from the hot‐water extracts of 16 carbonaceous chondrites from CM, CR, CO, CV, and CK groups. We observed high concentrations of meteoritic MCAs, with total carbon weight percentages which in some cases approached those of carbonates and insoluble organic matter. Moreover, we found that the concentration of MCAs in CR chondrites is higher than in the other meteorite groups, with acetic acid exhibiting the highest concentration in all samples. The abundance of MCAs decreased with increasing molecular weight and with increasing aqueous and/or thermal alteration experienced by the meteorite sample. The δ13C isotopic values of MCAs ranged from −52 to +27‰, and aside from an inverse relationship between δ13C value and carbon straight‐chain length for C3–C6 MCAs in Murchison, the 13C‐isotopic values did not correlate with the number of carbon atoms per molecule. We also observed racemic compositions of 2‐methylbutanoic acid in CM and CR chondrites. We used this novel analytical protocol and collective data to shed new light on the prebiotic origins of chondritic MCAs.
Impaired microvascular reactivity in gestational diabetes is associated with altered glycemic parameters
Authors: Rahman Aisyah , Munisamy Seetha , Ghaffar Nor Aliza , Mahmood Nik Zaki , Rasool Aida H. G.
Published: November 2018

Objectives

To assess microvascular reactivity and glycemic parameters in GDM compared to age and GA matched controls.

Methods

This study involved 21 GDM patients and 31 controls. Microvascular reactivity was assessed using LDF and PORH. Microvascular parameters; PORHmax, PORHpeak, and time to peak perfusion (Tp) were recorded after the release of 3 minutes’ upper arm occlusion. HOMA‐IR was performed to evaluate insulin resistance.

Results

Average age and GA for subjects were 32.9 years and 29.2 weeks. Mean FBG and a 2‐hour postprandial for GDM and controls were 4.87 ± 0.71 vs 3.99 ± 0.59 mmol/L; P < 0.001 and 9.50 ± 1.8 vs 5.67 ± 1.0 mmol/L; P < 0.001. Fasting insulin (13.88 ± 18.9 vs 8.37 ± 11.0 μLU/mL; P = 0.031) and HOMA‐IR (3.14 ± 4.6 vs 1.52 ± 2.2; P = 0.004) were higher in GDM. Tp was prolonged in GDM (16.27 ± 4.3 vs 13.86 ± 2.1 seconds; P = 0.011). Positive correlations were seen between Tp and FBG and 2‐hour postprandial levels.

Conclusion

Tp was prolonged in GDM compared to age‐matched controls, indicating impaired microvascular reactivity.
Demography and genetics suggest reversal of dolphin source‐sink dynamics, with implications for conservation
Authors: Manlik Oliver , Chabanne Delphine , Daniel Claire , Bejder Lars , Allen Simon J. , Sherwin William B.
Published: November 2018

The forecast for the viability of populations depends upon metapopulation dynamics: the combination of reproduction and mortality within populations, as well as dispersal between populations. This study focuses on an Indo‐Pacific bottlenose dolphin (Tursiops aduncus) population in coastal waters near Bunbury, Western Australia. Demographic modeling of this population suggested that recent reproductive output was not sufficient to offset mortality. Migrants from adjacent populations might make up this deficit, so that Bunbury would act as a “sink,” or net recipient population. We investigated historical dispersal in and out of Bunbury, using microsatellites and mitochondrial DNA of 193 dolphins across five study locations along the southwestern Australian coastline. Our results indicated limited gene flow between Bunbury and adjacent populations. The data also revealed a net‐dispersal from Bunbury to neighboring populations, with microsatellites showing that more than twice as many individuals per generation dispersed out of Bunbury than into Bunbury. Therefore, in historic times, Bunbury appears to have acted as a source population, supporting nearby populations. In combination with the prior finding that Bunbury is currently not producing surplus offspring to support adjacent populations, this potential reversal of source‐sink dynamics may have serious conservation implications for Bunbury and other populations nearby.
Two venom allergen‐like proteins, HaVAP1 and HaVAP2, are involved in the parasitism of Heterodera avenae
Authors: Luo Shujie , Liu Shiming , Kong Lingan , Peng Huan , Huang Wenkun , Jian Heng , Peng Deliang
Published: November 2018

Despite the fact that venom allergen‐like proteins (VAPs) have been identified in many animal‐ and plant‐parasitic nematodes, studies on VAPs in Heterodera avenae, which is an important phytonematode, are still in their infancy. Here, we isolated, cloned and characterized two VAPs, named HaVAP1 and HaVAP2, from H. avenae. The two encoded proteins, HaVAP1 and HaVAP2, harbour an SCP‐like domain each, but share only 38% identity with each other. HaVAP1 and HaVAP2 are expressed in subventral and dorsal oesophageal glands, respectively. HaVAP1 is expressed mainly at the early stages, whereas HaVAP2 accumulates principally at the late stages. Both HaVAP1 and HaVAP2 are secreted when expressed in Nicotiana benthamiana leaves, but HaVAP1 is delivered into chloroplasts, whereas HaVAP2 is translocated to the nucleus without signal peptides. Knocking down HaVAP1 increased the virulence of H. avenae. In contrast, silencing of HaVAP2 hampered the parasitism of H. avenae. Both HaVAP1 and HaVAP2 suppressed the cell death induced by BAX in N. benthamiana leaves. Moreover, HaVAP2 physically interacted with a CYPRO4‐like protein (HvCLP) of Hordeum vulgare in the nucleus of the plant. It is reasonable to speculate that the changes in the transcript of HvCLP are associated with HaVAP2 during the parasitism of H. avenae. All results obtained in this study show that both HaVAP1 and HaVAP2 are involved in the parasitism of H. avenae, but they possess different functions, broadening our understanding of the parasitic mechanism of H. avenae.