bluuebunny/crossref_metadata_2025 huggingface dataset:
Intergenerational associations of the approximate number system in toddlers and their parents
Authors: Navarro Monica G. , Braham Emily J. , Libertus Melissa E.
Published: January 2018

From birth, humans are able to discriminate quantities using the approximate number system (ANS). However, previous methods have only been suitable to examine ANS functioning in infancy and older children. The goals of this study were twofold: first, to modify an existing method of assessing ANS functioning for toddlerhood; and second, to investigate individual differences in toddlers’ ANS performance by examining correlations with their parents’ ANS acuity. Using a preferential looking paradigm, we found that 1‐ to 3‐year‐olds (N = 46) looked significantly longer to numerically changing images compared to numerically constant ones suggesting that the paradigm is a suitable measure of ANS functioning in toddlerhood. Furthermore, we found a positive relation between toddlers’ ANS performance and that of their parents (assessed using a non‐symbolic number comparison task) independent of children's vocabulary or parents’ perceived math ability or preference for math. These findings are consistent with a specific intergenerational transmission of the ANS.

Statement of contribution

What is already known on this subject?

Past methods used to examine ANS functioning were only suitable for infants and older children.

Little research has examined sources underlying individual difference in ANS acuity.

What does this study add?

We developed a preferential looking task to assess ANS functioning in toddlerhood.

Individual differences in toddlers’ ANS functioning are correlated with their parents’ ANS acuity.
Megakaryocytes harbour the del(5q) abnormality despite complete clinical and cytogenetic remission induced by lenalidomide treatment
Authors: Scharenberg Christian , Jansson Monika , Saft Leonie , Hellström‐Lindberg Eva
Published: January 2018

The mechanisms underlying lenalidomide‐resistance of del(5q) MDS stem cells remain to be elucidated and may include cell‐intrinsic as well as microenvironmental causes. Abnormal hypolobated megakaryocytes constitute one of the hallmarks of del(5q) MDS. We hypothesized that these cells have potential implications for the regulation of haematopoietic stem cells (HSC) similarly to what has recently been described for megakaryocytes in the murine system. Therefore, we conducted a study to determine the response of abnormal hypolobated megakaryocytes to lenalidomide therapy. We studied lenalidomide‐treated patients in the MDS‐004 trial as well as a cohort seen at our institution. Morphological evaluation at time of complete cytogenetic remission (CCyR) demonstrated the persistence of hypolobated megakaryocytes in all evaluable patients (n = 9). Furthermore, we provide evidence that the abnormal hypolobated morphology is restricted to del(5q) megakaryocytes, both at diagnosis and during CCyR. Using fluorescence in situ hybridisation analysis on flow‐sorted stem‐ and progenitor populations, we observed a similar degree of clonal involvement in megakaryocyte‐erythroid‐progenitors as in HSC. Taken together, our findings suggest that megakaryocyte morphology might aid in the evaluation of patients where discontinuation of lenalidomide is considered and offers interesting hypotheses for further investigation of lenalidomide resistance.
How I manage red cell transfusions in patients with sickle cell disease
Authors: Rees David C. , Robinson Susan , Howard Jo
Published: January 2018

Sickle cell disease is one of the commonest serious inherited diseases in the world, and red cell transfusion is still one of the few effective treatments for acute and chronic complications. Transfusion corrects anaemia and dilutes out the number of red cells able to cause vaso‐occlusion and vascular damage. Urgent red cell transfusions are used to correct acute anaemia, treat acute chest syndrome and patients with acute neurological symptoms. We use elective transfusions preoperatively for moderate risk surgery, and in some pregnant women. There is good evidence for the use of long‐term regular transfusions in primary stroke prevention, with the aim of keeping the percentage of sickle haemoglobin below 30%. Long‐term transfusions are also used in secondary stroke prevention, and the management of progressive organ damage, including renal impairment and pulmonary hypertension. Blood needs to be matched for ABO, RH and Kell, although alloantibodies may still develop and require more careful, extended cross‐matching. Delayed haemolytic transfusion reactions are relatively common, difficult to diagnose and manage, and potentially fatal.
Sink‐to‐source: Influence of offshore dynamics on upstream processes
Authors: Abeyta Antoinette , Foreman Brady Z. , Swenson John B. , Paola Chris , Mohr Jeré
Published: January 2018

When we model fluvial sedimentation and the resultant alluvial stratigraphy, we typically focus on the effects of local parameters (e.g., sediment flux, water discharge, grain size) and the effects of regional changes in boundary conditions applied in the source region (i.e., climate, tectonics) and at the shoreline (i.e., sea level). In recent years this viewpoint has been codified into the “source‐to‐sink” paradigm, wherein major shifts in sediment flux, grain‐size fining trends, channel‐stacking patterns, floodplain deposition and larger stratigraphic systems tracts are interpreted in terms of (1) tectonic and climatic signals originating in the hinterland that propagate downstream; and (2) eustatic fluctuation, which affects the position of the shoreline and dictates the generation of accommodation. Within this paradigm, eustasy represents the sole means by which downstream processes may affect terrestrial depositional systems. Here, we detail three experimental cases in which coastal rivers are strongly influenced by offshore and slope transport systems via the clinoform geometries typical of prograding sedimentary bodies. These examples illustrate an underdeveloped, but potentially important “sink‐to‐source” influence on the evolution of fluvial‐deltaic systems. The experiments illustrate the effects of (1) submarine hyperpycnal flows, (2) submarine delta front failure events, and (3) deformable substrates within prodelta and offshore settings. These submarine processes generate (1) erosional knickpoints in coastal rivers, (2) increased river channel occupancy times, (3) rapid rates of shoreline movement, and (4) localized zones of significant offshore sediment accumulation. Ramifications for coastal plain and deltaic stratigraphic patterns include changes in the hierarchy of scour surfaces, fluvial sand‐body geometries, reconstruction of sea‐level variability and large‐scale stratal geometries, all of which are linked to the identification and interpretation of sequences and systems tracts.
Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma through suppression of CD44s and the ERK1/2 pathway
Authors: Hou Helei , Ge Chao , Sun Hefen , Li Hong , Li Jinjun , Tian Hua
Published: January 2018

Tunicamycin (TM) is an N‐linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated. In our previous studies, we found that TM reversed drug resistance and improved the efficacy of combination treatments for hepatocellular carcinomas (HCC). Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects. Our results showed that TM inhibited cell proliferation and migration as well as induced apoptosis of hepatocellular carcinoma cells. TM inhibited proliferation of HCC cells by inducing cell apoptosis and cell cycle arrest at the G2/M phase. Meanwhile, TM inhibited migration of HCC cells by suppressing CD44s‐mediated epithelial‐mesenchymal transition (EMT). TM inhibited migration and invasion of HCC cells by decreasing CD44 expression and altering its glycosylation. In addition, CD44s is involved in promoting EMT and is associated with a poor prognosis in HCC patients. Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression‐associated cell migration. The ability of TM to inhibit cell migration and invasion was enhanced or reversed in CD44s knockdown cells and cells overexpressing CD44s, respectively. The MEK/ERK inhibitor U0126 and TM inhibited hyaluronic acid‐induced cell migration in HCC cells. Furthermore, TM inhibited exogenous transforming growth factor beta (TGF‐β)‐mediated EMT by an ERK1/2‐dependent mechanism and restored the TGF‐β‐mediated loss of E‐cadherin. In summary, our study provides evidence that TM inhibits proliferation and migration of HCC cells through inhibition of CD44s and the ERK1/2 signaling pathway.
Does public transportation improve the accessibility of primary dental care in São Paulo, Brazil?
Authors: Yuen Aidan , Martins Rocha Carla , Kruger Estie , Tennant Marc
Published: January 2018

Objective

Advances in geospatial technologies have recognized the role of geographic distance as a barrier to healthcare accessibility. Frequent transportation is supposed to buffer issues with distance, while infrequent services impede the uptake of care. The role of public transportation on the accessibility of health care—including oral health care—is not well elucidated in the context of megacities, such as the municipality of São Paulo, Brazil. This study aimed to compare the supply of public transportation to primary dental clinics and the population between advantaged and disadvantaged areas in São Paulo city.

Methods

A total of 4101 primary dental clinics in São Paulo city were identified and geocoded. Geographic coordinates were also retrieved for the 19 242 bus stops, 56 commuter rail stations and 64 rapid transit stations. Clinic locations and transport points were integrated with the city's 19 128 constituent census tracts—each containing sociodemographic data on the 11 252 204 residents—using Geographic Information Systems (GIS).

Results

Almost all clinics were located within 0.5 km of public transportation. Half of all clinics were within 0.5 km of high‐frequency transport points, and three‐quarters were within 1 km. Likewise, 99% of the population resided within 0.5 km of any public transportation. However, only 22% were within 0.5 km of high‐frequency options, and half were within 1 km. Those within 0.5 km of high‐frequency points had higher average monthly household incomes and lower illiteracy rates, with lower proportions of children and ethnic minorities, and higher proportions of older people.

Conclusion

Clinics and populations in sociodemographically disadvantaged tracts have poorer public transportation links in São Paulo city.
Dissection of a circulating CD3+CD20+ T cell subpopulation in patients with psoriasis
Authors: Niu J , Zhai Z , Hao F , Zhang Y , Song Z , Zhong H
Published: January 2018

CD3+CD20+ T cells are a population of CD3+ T cells that express CD20 and identified in healthy donors and autoimmune diseases. However, the nature and role of these cells in patients with psoriasis remain unclear. In this study, we aimed to investigate the level, phenotype, functional and clinical relevance of CD3+CD20+ T cells in the peripheral blood of patients with psoriasis. We found that a small subset of CD3+ T cells expressed CD20 molecule in the peripheral blood of patients with psoriasis, and their levels were similar to those in healthy donors. Circulating CD3+CD20+ T cells in patients with psoriasis were enriched in CD4+ cells and displayed an activated effector phenotype, as these cells contained fewer CD45RA+-naive and CCR7+ cells with increased activity than those of CD3+ T cells lacking CD20. In addition, compared with healthy donors, circulating CD3+CD20+ T cells in patients with psoriasis produced more cytokines, interleukin (IL)-17A, tumour necrosis factor (TNF)-α and IL-21, but not IL-4 and IFN-γ. Furthermore, a significantly positive correlation was found between the levels of IL-17A, TNF-α and IL-21-production CD3+CD20+ T cells with Psoriasis Area and Severity Index scores. Our findings suggest that CD3+CD20+ T cells may play a role in the pathogenesis of psoriasis.
The CDK inhibitor purvalanol A induces neutrophil apoptosis and increases the turnover rate of Mcl-1: potential role of p38-MAPK in regulation of Mcl-1 turnover
Authors: Phoomvuthisarn P , Cross A , Glennon-Alty L , Wright H L , Edwards S W
Published: January 2018

Human neutrophils are terminally differentiated cells that do not replicate and yet express a number of enzymes, notably cell cycle-dependent kinases (CDKs), that are associated normally with control of DNA synthesis and cell cycle progression. In neutrophils, CDKs appear to function mainly to regulate apoptosis, although the mechanisms by which they regulate this process are largely unknown. Here we show that the CDK2 inhibitor, purvalanol A, induces a rapid decrease in myeloid cell leukaemia factor-1 (Mcl-1) levels in human neutrophils and peripheral blood mononuclear cells (PBMCs), but only induces apoptosis in neutrophils which are dependent upon expression on this protein for survival. This rapid decrease in cellular Mcl-1 protein levels was due to a purvalanol A-induced decrease in stability, with the half-life of the protein decreasing from approximately 2 h in control cells to just over 1 h after addition of the CDK2 inhibitor: it also blocked the granulocyte–macrophage colony-stimulating factor (GM-CSF)-dependent stabilization of Mcl-1. Purvanalol A blocked GM-CSF-stimulated activation of extracellular-regulated kinase (Erk) and signal transducer and activator of transcription (STAT)-3, and stimulated an additive activation of protein kinase B (Akt) with GM-CSF. Purvalanol A alone stimulated a rapid and sustained activation of p38-mitogen-activated protein kinase (MAPK) and the pan p38-MAPK inhibitor, BIRB796, partly blocked the purvalanol A-induced apoptosis and Mcl-1 loss. These novel effects of purvalanol A may result, at least in part, from blocking GM-CSF-mediated Erk activation. In addition, we propose that purvalanol A-induced activation of p38-MAPK is, at least in part, responsible for its rapid effects on Mcl-1 turnover and acceleration of neutrophil apoptosis.
Clinical value of 18FDG PET/CT in screening for distant metastases in head and neck squamous cell carcinoma
Authors: Deurvorst S.E. , Hoekstra O.S. , Castelijns J.A. , Witte B.I. , Leemans C.R. , de Bree R.
Published: January 2018

Objectives

The detection of distant metastases is of major importance in management of head and neck squamous cell carcinoma patients.

Design

All patients underwent 18FDG PET/CT for the detection of distant metastases.

Setting

Retrospective single‐centre study.

Participants

Head and neck squamous cell carcinoma patients with high‐risk factors for distant metastases.

Main outcome measures

Accuracy of 18FDG PET/CT for the detection of distant metastases using clinical development of distant metastases and a minimal follow‐up of twelve months as reference standard. Comparison of overall survival between patients diagnosed with distant metastases during initial screening and patients diagnosed with distant metastases during follow‐up.

Results

In 23 (12%) of the 190 patients, 18FDG PET/CT detected distant metastases at screening. Sensitivity and negative predictive value were 46.2% (95% CI 32.6‐59.7) and 82.6% (95% CI 76.8‐88.5). No difference in median overall survival from the time of distant metastases detection was found between patients diagnosed with DM during work‐up or during follow‐up.

Conclusions

In head and neck squamous cell carcinoma patients with high‐risk factors, 18FDG PET/CT has a high negative predictive value for the detection of distant metastases and should be used in daily clinical practice, although the sensitivity is limited when long‐term follow‐up is used as reference standard.
The Display of Baroque Ivories in the Bayerisches Nationalmuseum from the Foundation of the Museum in 1855 to the Present (2018)
Authors: Burk Jens Ludwig
Published: January 2018

This article reviews the display of Baroque ivories in the Bayerisches Nationalmuseum in Munich (hereafter BNM), drawing on the history of the museum in general and a festschrift that documented the museum's history from the 1870s to 2005 (Eikelmann 2006) ‐ to explore the place of Baroque ivories in various generations of display. Starting with a comprehensive historical overview on the formation of the different collections of ivories that were to be united in the BNM, the survey will primarily focus on the differences in conception, presentation, aesthetic decisions and didactic aims. The different exhibition rooms are partially documented through historical photographs, surviving object lists for the permanent exhibition rooms and the published visitors’ guides to the collection, starting with the first volume in 1868. Somewhat exceptionally, the exhibition display was also the subject of an article published in 1924 by Rudolf Berliner (–1967), at the time the BNM′s curator responsible for the ivory collection. That article introduced his ideas about the display of the ivories. Together all these sources bear witness to the metamorphoses of the presentation of the Baroque ivories from the first building of the BNM in Maximilianstrasse (Figure 1) originally founded by King Maximilian II. Joseph of Bavaria in 1855 and opened to the public in 1867, to the second building of the museum in Prinzregentenstrasse (Figure 2), opened to the public in 1900. Finally, this article tracks the fundamental changes of display in the second and present building of the BNM that can be followed throughout the course of the 20th up to the beginning of the 21st century. In the wake of the installation of a new permanent exhibition for the Baroque ivories on the upper level of the BNM, opening summer of 2018, the survey also aims to justify the decisions made in the planning of these galleries: retaining traditions and aiming to suggest new ideas for the display of the Baroque ivories.
Walking with Elephants: Stories of Ivories in a Museum of Ancient Art
Authors: Castronovo Simonetta , Ferla Anna La
Published: January 2018

Palazzo Madama – Museo Civico d'Arte Antica in Turin (Italy) owns nearly 300 ivories from the XII to the XVIIIth century, mostly coming from the Royal Treasure of the Savoy Palace in Turin. In March 2016 the museum completely renovated the ivories’ showcases. In parallel the curators went through a deep art historical research on the museum's ivories which converged in a systematic catalogue of the collection. Even being a “traditional” museum of ancient art, Palazzo Madama works on its collections with a wider and transversal approach, drawing in disciplines such as antropology, history of culture and chemistry and experiencing projects of storytelling. The museum has carried out in the last five years series of conferences, exhibitions and public education activities dedicated to the ritual and symbolic use of ivory over the centuries: with an overview from the past to the present and across the three continents of Europe, Asia and Africa, anthropologists, historians and representatives of the local communities have driven the dialogue to raise awareness on a medium which “walks” with humanity from its origin. The Museum believes that, in order to introduce policies to save elephants and to combat poaching, it is necessary for citizens to see and understand ivory artefacts duly explained.
Species–area curve and distance–decay relationships indicate habitat thresholds of ectomycorrhizal fungi in an old‐growth Pseudotsuga menziesii landscape
Authors: Kranabetter J. M. , Berch S. M. , MacKinnon J. A. , Ceska O. , Dunn D. E. , Ott P. K.
Published: January 2018

Aim

Ectomycorrhizal fungi (EMF) are a diverse and essential biota of forests that are vulnerable to species loss through reductions in late‐seral habitat. We examined how the spatial ecology of this biota, particularly distance–decay and species–area relationships, could better inform habitat thresholds for EMF conservation planning.

Location

Southeast Vancouver Island near Victoria, British Columbia, Canada.

Methods

Using a stratified sampling design, 11 plots (0.15 ha in size) were established at 0.05–17.5 km apart across 2,800 ha of mesic old‐growth Pseudotsuga menziesii var. menziesii and Tsuga heterophylla forests. EMF communities were compiled through molecular analysis of root tips and sporocarps.

Results

The EMF community was comprised of many Cortinarius, Piloderma, Russula and Tricholoma species typical of mesotrophic habitat. A total of 238 EMF species were observed, of which 86 species were detected only once. The ratio of average species richness per plot (84 taxa) to total richness was low at 0.35, and inherent stochasticity of the EMF community was estimated to be 31% community dissimilarity for species incidence. Distance decay of EMF communities was nonlinear, with an estimated slope break at 2.6 km, followed by a largely unchanging trend in β‐diversity. Accumulated species–area curves were fitted best by the cumulative Weibull sigmoid model, and the asymptote (367 species) at approx. 50 ha was consistent with nonparametric estimates of γ‐diversity (342–362 spp.).

Main conclusions

Old‐growth forests host an impressive amount of EMF diversity, and many of the Ramaria, Inocybe and Russula species are likely to be endemic to the Pacific Northwest. Both niche‐ and neutral‐based processes influenced EMF community composition, resulting in a minimum threshold of 50 ha (1.8% of the sample area) for capturing γ‐diversity. These spatial patterns will help design and evaluate conservation efforts, such as retention forestry, to sustain fully diverse EMF communities over managed landscapes.
Effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies on new‐onset diabetes mellitus and glucose metabolism: A systematic review and meta‐analysis
Authors: Cao Ye‐Xuan , Liu Hui‐Hui , Dong Qiu‐Ting , Li Sha , Li Jian‐Jun
Published: January 2018

Aims

To investigate the effect of two clinically applied proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9‐mAbs) on glycaemia and new‐onset diabetes mellitus (NODM).

Materials and Methods

PubMed, MEDLINE, Embase, Cochrane databases and ClinicalTrials.gov websites were systematically searched for randomized controlled trials that reported data on fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) or NODM incidence. Risk ratios (RRs) for NODM and mean difference (MD) for FPG and HbA1c with 95% confidence intervals (CIs) were calculated using a fixed‐effect model. Heterogeneity was examined using the I2 statistic and potential publication bias was assessed using funnel plots and Egger’s test.

Results

A total of 18 studies including 26 123 participants without diabetes were identified. No significant difference was observed in the PCSK9‐mAb treatment groups in terms of NODM (RR 1.05, 95% CI 0.95‐1.16), FPG (MD 0.00 mmol/L, 95% CI −0.02 to 0.02) or HbA1c (MD 0.00% [0 mmol/L], 95% CI −0.01 to 0.01) compared with control groups. Subgroup (PCSK9‐mAb type, participant characteristics, treatment duration, treatment method and differences in control treatment) and sensitivity analyses did not significantly alter the results. Meta‐regression analyses showed that risk of NODM was not associated with baseline age, baseline body mass index (BMI), proportion of men, treatment duration or percent LDL cholesterol reduction.

Conclusions

Alirocumab and evolocumab, two types of PCSK9‐mAb approved by the US Food and Drug Administration and the European Medicines Agency, had no significant impact on NODM and glucose homeostasis, regardless of PCSK9‐mAb type, participant characteristics, treatment duration, treatment method and differences in control treatment. Baseline age, BMI, proportion of men, treatment duration, and percent change of LDL cholesterol did not influence diabetes risk.
Dulaglutide treatment results in effective glycaemic control in latent autoimmune diabetes in adults (LADA): A post‐hoc analysis of the AWARD‐2, ‐4 and ‐5 Trials
Authors: Pozzilli Paolo , Leslie Richard D. , Peters Anne L. , Buzzetti Raffaella , Shankar Sudha S. , Milicevic Zvonko , Pavo Imre , Lebrec Jeremie , Martin Sherry , Schloot Nanette C.
Published: January 2018

Aims

Patients with a type‐2‐diabetes (T2D) phenotype positive for glutamic acid decarboxylase antibodies (GADA) represent the majority of cases of latent autoimmune diabetes of the adult (LADA). The GLP‐1 receptor agonist dulaglutide, recently introduced for treatment of T2D, has yet to be evaluated in LADA patients. Our primary objective was to evaluate the effect of dulaglutide on glycaemic control (HbA1c) in GADA‐positive LADA vs GADA‐negative T2D patients.

Methods

A post‐hoc analysis was performed using data from 3 randomized phase 3 trials (AWARD‐2,‐4,‐5; patients with GADA assessment) which were part of the dulaglutide clinical development programme in T2D. LADA patients were identified by GADA ≥5 IU/mL (ELISA). Changes in HbA1c during 12 months of treatment with dulaglutide or comparator were analysed using mixed‐effect model repeated measures.

Results

Of 2466 adults tested for GADA (dulaglutide, 1710; glargine, 298; sitagliptin, 294; placebo, 164), 2278 (92.4%) were GADA‐negative and 188 (7.6%) were GADA‐positive, including 58 GADA‐high patients (> 200 IU/mL) and 130 GADA‐low patients (≤200 and ≥5 IU/mL). Overall, baseline parameters were comparable between the groups.

Dulaglutide resulted in comparable HbA1c reductions in GADA‐negative (LS mean change [95%CI], −1.09% [−1.15, −1.03]) and GADA‐positive patients (−0.94% [−1.15, −0.72]) at 12 months. HbA1c reductions were numerically, but not statistically, significantly larger in GADA‐low patients (−1.02% [−1.26, −0.78]) vs GADA‐high patients (−0.72% [−1.21,−0.24]) at 12 months. Similar outcomes were observed at 3 and 6 months.

Conclusions

These data are the first to indicate that dulaglutide was effective in reducing HbA1c in LADA patients.
A Western dietary pattern is associated with elevated level of high sensitive C‐reactive protein among adolescent girls
Authors: Khayyatzadeh Sayyed Saeid , Bagherniya Mohammad , Fazeli Mostafa , Khorasanchi Zahra , Bidokhti Mina Safari , Ahmadinejad Malihe , Khoshmohabbat Somaieh , Arabpour Mahla , Afkhamizadeh Mozhgan , Ferns Gordon A. , Masoudifar Maryam , Ghayour‐Mobarhan Majid
Published: January 2018

Background

Serum high sensitive C‐reactive protein (hs‐CRP), is an indicator of low‐grade inflammation, and is associated with several non‐communicable diseases. The effects of diet on inflammation have not been extensively investigated, particularly among adolescents. We aimed to examine the association between major dietary patterns and elevated serum level of hs‐CRP among Iranian adolescent girls.

Materials and methods

In this cross‐sectional study, a total of 670 adolescent girls were recruited from several schools in different areas of Mashhad and Sabzevar cities, Iran. The dietary intakes of study participants were collected using a 147‐item food frequency questionnaire. To identify major dietary patterns based on the 40 food groups, we used principal component analysis. Serum concentration of hs‐CRP was measured using commercial kits and the BT‐3000 auto‐analyser. To investigate the association between dietary patterns and elevated serum level of hs‐CRP, we used logistic regression analysis.

Results

Three specific dietary patterns were identified: (i) healthy, (ii) traditional and (iii) western dietary patterns. A significant association was found between more adherence to Western dietary pattern and elevated serum level of hs‐CRP (OR: 1.58; 95% CI: 1.02‐2.42, P‐trend = .03); these association remained significant after adjustment for potential confounders. However, there was no significant relationship between healthy and traditional dietary patterns and elevated serum level of hs‐CRP.

Conclusion

Our results indicate that there is a significant positive association between more adherence to Western dietary pattern and higher serum levels of hs‐CRP among Iranian adolescent girls. Further studies, particularly longitudinal intervention studies may be required to clarify these relationships.
Expression pattern of PD‐L1 and PD‐L2 in classical Hodgkin lymphoma, primary mediastinal large B‐cell lymphoma, and gray zone lymphoma
Authors: Tanaka Yosuke , Maeshima Akiko Miyagi , Nomoto Junko , Makita Shinichi , Fukuhara Suguru , Munakata Wataru , Maruyama Dai , Tobinai Kensei , Kobayashi Yukio
Published: January 2018

Objectives

We aimed at investigating the relationship between classical Hodgkin lymphoma (cHL), primary mediastinal large B‐cell lymphoma (PMBL), and gray zone lymphoma (GZL) with intermediate characteristics between cHL and PMBL, from the perspective of the aberration in programed cell death 1 and the programed death ligands (PDLs) network.

Methods

We explored the expression levels of PDLs and chromosomal anomalies in 67 cases: 34 cases with cHL, 20 with PMBL, and 13 with GZL, using immunohistochemical analyses and Fluorescence In Situ Hybridization (FISH).

Results

Twenty‐one cHL (62%), 3 PMBL (15%), and 6 GZL (46%) cases showed staining to PD‐L1 antibodies in more than 70% of tumor cells. Two cHL (6%), 10 PMBL (50%), and 3 GZL (23%) cases were not stained by PD‐L1 antibodies. Patients over 40 years old manifest more frequent expression of PD‐L1 in cHL. Proportion of tumors stained by PD‐L2 antibody was increased in PMBL. FISH analyses with a PD‐L1/PD‐L2 probe detected 5 amplification, 1 gain, and 7 polysomy cases in cHL, 1 amplification and 1 polysomy case in GZL, and amplification in 1 PMBL case.

Conclusion

We identified increased staining of PD‐L1 in cHL and that of PD‐L2 in PMBL. GZL had a pattern similar to that of cHL.
Zebrafish larvae as a model to demonstrate secondary iron overload
Authors: Nasrallah Gheyath K. , Younes Nadin N. , Baji Missbah H. , Shraim Amjad M. , Mustafa Ibrahim
Published: January 2018

Objectives

Thalassemia is the most common genetically inherited blood disorder arising from a defect in hemoglobin production, resulting in ineffective erythropoiesis and severe hemolytic anemia. While transfusion therapy corrects the anemia, it gives rise to secondary iron overload. Current iron chelation therapy performed using deferoxamine, and the efficiency of this drug was demonstrated here using the zebrafish animal model.

Methods

Zebrafish larvae were exposed for 3 days to iron [100 μmol L−1ferric ammonium citrate; 3‐6 days post fertilization (dpf)]. Then, iron treated larvae were exposed to 100 μmol L−1deferoxamine for 3 days (6‐9 dpf). Total tissue iron concentration in the whole larvae, assessed by three different assays; inductively coupled plasma mass spectrometry, colorimetry (spectrophotometry), and microscopy using iron staining followed by imaging and quantification.

Results

The three assays showed that iron treatment alone resulted in a significant increase in total iron. Deferoxamine treatment of the iron‐loaded zebrafish larvae showed a significant decrease in total iron concentration.

Conclusion

This study presented a clear evidence of the effectiveness of zebrafish larvae to use as a tool to study iron overload and open the door for studying the efficiency of potential new iron chelating compounds other than commercially available ones.
Agmatine co‐treatment attenuates allodynia and structural abnormalities in cisplatin‐induced neuropathy in rats
Authors: Donertas Basak , Cengelli Unel Cigdem , Aydin Sule , Ulupinar Emel , Ozatik Orhan , Kaygisiz Bilgin , Yildirim Engin , Erol Kevser
Published: January 2018

Cisplatin is a widely used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well‐known side effect of cisplatin and has potential to result in limiting and/or reducing the dose, decreasing the quality of life. Thus, effective treatments are needed. Agmatine is an endogenous neuromodulator that has been shown to exert antiallodynic effects in various animal studies. The first aim of this study was to investigate the in vitro effects of agmatine on cisplatin‐induced neurotoxicity. Primary cultures of dorsal root ganglia (DRG) which are the primary target of drug injury were prepared. DRG cells were incubated with cisplatin (100, 200, 500 μm). Then, agmatine (10, 100, 500 μm) was administered with the submaximal concentration of cisplatin. Cisplatin caused concentration‐dependent neurotoxicity, and agmatine did not alter this effect. The second aim was to investigate the effects of agmatine on cisplatin‐induced peripheral neuropathy in rats and the influence of nitric oxide synthase (NOS) inhibitor, L‐NAME, in this effect. Female Sprague Dawley rats received intraperitoneal saline (control), cisplatin (3 mg/kg), cisplatin+agmatine (100 mg/kg), or cisplatin+agmatine+L‐NAME (10 mg/kg) once a week for 5 weeks. The mechanical allodynia, hot plate, and tail clip tests were performed, and DRG cells and sciatic nerves were analyzed. Agmatine and agmatine+L‐NAME combination attenuated CIS‐induced mechanical allodynia and degeneration in DRG cells and sciatic nerves. However, L‐NAME did not potentiate the antiallodynic or neuroprotective effect of agmatine. These findings indicate that agmatine co‐administration ameliorates cisplatin‐induced neuropathy and may be a therapeutic alternative.
Domperidone upregulates dopamine receptor expression and stimulates locomotor activity in larval zebrafish (Danio rerio)
Authors: Shontz E. C. , Souders C. L. , Schmidt J. T. , Martyniuk C. J.
Published: January 2018

Dopamine (DA) plays a significant role in cognition, motor function and social behavior. The objectives of this study were to (1) quantify the temporal expression of transcripts (DA receptors, transporters and tyrosine hydroxylase) associated with DA signaling during early stages of zebrafish development and (2) determine their expression profiles following treatment with a D2 receptor antagonist domperidone (DMP). We also assessed locomotor behavior following treatment with DMP using alternating periods of light and dark (ie, dark photokinesis), as DA plays a key role in behavior. Relative expression levels of transcripts that were investigated and related to the DA system were detected after the first 24 hours postfertilization (hpf). Some DA receptor transcripts (eg, drd4c) increased in abundance earlier in the embryo compared with other receptors (eg, drd3), suggesting that DA receptor paralogs may have unique roles in development. Treatment of larvae with DMP resulted in the upregulation of DA receptor transcripts (ie, drd1, drd7, drd4b, drd4c) and DA transporter 1 (ie, slc6a3), and it is hypothesized that upregulation of genes related to the DA system is a compensatory neurophysiological response to DA receptor antagonism. Larval activity during dark photokinesis (measured by distance traveled) was also elevated by DMP. We hypothesize that behavioral responses observed with DMP may be related to the regulation of deep brain photoreception in zebrafish (Danio rerio) (ZF) larvae by DA.
Interactive effects of LPS and dentine matrix proteins on human dental pulp stem cells
Authors: Widbiller M. , Eidt A. , Wölflick M. , Lindner S. R. , Schweikl H. , Hiller K.‐A. , Buchalla W. , Galler K. M.
Published: January 2018

Aim

To investigate the combinatorial effects of lipopolysaccharide (LPS) and extracted dentine matrix proteins (eDMP) on regenerative and inflammatory responses in human dental pulp stem cells (DPSCs).

Methodology

Culture media were supplemented with several concentrations of LPS, eDMP and combinations of both. Cell viability was assessed over 1 week by MTT assay; cell survival was evaluated after 24 h and 7 days by flow cytometry. The expression of mineralization‐associated marker genes was determined by real‐time quantitative polymerase chain reaction (RT‐qPCR). To analyse the inflammatory response, secretion of interleukin 6 (IL‐6) was quantified in the initial and the late phase of cell culture by enzyme‐linked immunosorbent assay (ELISA). Data were treated nonparametrically and Mann–Whitney U‐tests were performed to compare all experimental groups (α = 0.05).

Results

Whereas LPS had no impact on viability, eDMP led to a concentration‐dependent decrease, which was significant after 7 days (P ≤ 0.024). A moderate decline of cell survival induced by LPS was detected after 48 h (P ≤ 0.026), whereas eDMP was able to reverse this effect. eDMP alone caused increased expression of tested marker genes, LPS had no regulatory effect. Combined eDMP and LPS induced an upregulation of collagen type I and osteocalcin, whereas expression levels of dentine matrix acidic phosphoprotein and dentine sialophosphoprotein were similar to the control. IL‐6‐secretion was increased by LPS over time. eDMP markedly elevated initial production of IL‐6 (P ≤ 0.002), but suppressed LPS‐induced cytokine production in the later phase.

Conclusions

Lipopolysaccharide did not affect cell viability but interfered with odontoblast‐like cell differentiation of DPSCs. Proteins from the dentine matrix may have a protective effect, attenuate the detrimental impact of LPS and thus play an important role during pulp repair.
Systemic bone marker expression induced by grey and white mineral trioxide aggregate in normal and diabetic conditions
Authors: de Azevedo Queiroz I. O. , Mello W. G. , Martins C. M. , Dal Fabbro R. , Narciso L. G. , Massunari L. , Cintra L. T. A. , Ervolino E. , Gomes‐Filho J. E.
Published: January 2018

Aim

To investigate the relationship between diabetes mellitus and local/systemic effects of both grey and white mineral trioxide aggregate (MTA) Angelus on bone marker expression.

Methodology

Wistar rats were divided into two groups: healthy and diabetic (Alloxan induced), which were further divided into three subgroups (control, GMTA Angelus and WMTA Angelus). Polyethylene tubes filled with MTA materials or empty tubes were implanted in dorsal connective tissue. On days 7 and 30, blood samples were collected for calcium, phosphorus and ALP measurement. The animals were euthanized; implanted tubes were removed and processed for immunohistochemical analysis of osteocalcin (OCN) and osteopontin (OPN). Kruskal–Wallis followed by Dunn's multiple comparison test was performed for nonparametric data, and anova followed by Tukey's test for parametric data.

Results

No difference in systemic serum calcium levels between both groups was observed. On day 7, serum phosphorus levels within the WMTA healthy group were higher than that of the diabetic group. On day 30, healthy rats exhibited lower phosphorus levels than diabetic ones. At both time points, the diabetic group was associated with more ALP activity than the healthy group. Immunohistochemical analyses of the healthy group revealed OCN‐ and OPN‐positive cells in the presence of both MTA materials. However, under diabetic conditions, both OCN and OPN were absent.

Conclusion

Both MTA materials were associated with an increase in serum calcium, phosphorus and ALP, suggesting a potential systemic effect, along with triggered differentiation of OCN‐ and OPN‐positive cells. Moreover, in diabetic conditions, an inhibitory effect on MTA‐induced differentiation of OCN‐ and OPN‐positive cells was detected.
Pathogenesis and treatment options for chemotherapy‐induced alopecia: a systematic review
Authors: Rubio‐Gonzalez Belen , Juhász Margit , Fortman Jamie , Mesinkovska Natasha Atanaskova
Published: January 2018

Chemotherapy‐induced alopecia (CIA) is one of the most troubling long‐lasting side effects of cancer treatment. An estimated 65% of patients undergoing classic chemotherapy will experience hair loss, which is an extremely upsetting adverse event for many. CIA has been traditionally considered to be a diffuse, nonscarring alopecia; however, there are increasing reports of permanent hair loss post chemotherapy. Despite its large impact on patients, there are few proven treatments for CIA. Recent advancements in understanding the pathogenesis of hair loss are promising novel preventative and therapeutic strategies. Currently, scalp cooling during chemotherapy is the most effective preventive intervention with response rates ranging from 50 to 80%. To avoid patient morbidity, clinicians should be aware of the pathogenesis of CIA, characteristic patterns of hair loss associated with specific drug regimens, preventive measures that may be taken, and therapeutic options post chemotherapy. The following represents an updated systematic review of CIA, including characteristic clinical patterns, pathophysiology of the disease, therapeutic approaches, as well as a cost‐effective analysis to assess the significance of this toxicity.
Clinical features and management of schwannoma affecting the upper and lower lips
Authors: Sitenga Jenna , Aird Gregory , Vaudreuil Adam , Huerter Christopher J.
Published: January 2018

Head and neck schwannomas comprise 25–40% of all schwannomas, with presentation on the lips as the rarest and most surgically complicated site for perioral tumors. A systematic literature review was conducted to include 21 cases of patients with schwannoma of the upper or lower lips. The majority of patients presented with a single, painless, well‐encapsulated nodule on the upper or lower lips. The nodules were consistently slow‐growing, with an average 29.3 months from symptom onset to clinical presentation. Most cases were complicated by profound cosmetic disfigurement as well as dysphagia, dysarthria, snoring, and/or sleep apnea. Overall, histological analysis was consistent with classic schwannoma, and all cases were treated via complete surgical excision, and for malignant tumors, additional therapy was utilized. All but four cases achieved full remission by final follow‐up. Recurrence rate for benign lip schwannomas was 5.3%, which is remarkably different from the standard recurrence rate of 8–24% for benign peripheral schwannomas. Additionally, the proportion of malignant tumors was greater for lip schwannomas than other schwannomas. Lip schwannomas demonstrate different characteristics than schwannomas from other locations on the body, and these remarkable differences highlight significant implications for clinical practice. Complete excision is the primary mode of treatment with overall excellent postoperative prognosis and rare instances of recurrence. Given the rarity of this tumor, this review of available cases serves to comprehensively describe clinical presentation and surgical treatment approaches to upper and lower lip schwannomas.
Monomeric phenolics in different parts of high‐acid apple (Malus sieversii f. niedzwetzkyana (Dieck) Langenf): a promising source of antioxidants for application in nutraceuticals
Authors: Lin Lianzhu , Peng An , Yang Kun , Zou Ying
Published: January 2018

The high‐acid apple (Malus sieversii f. niedzwetzkyana (Dieck) Langenf) possessing deep red peel and light red flesh is widely distributed in China. To determine if a useful apple variety is being ignored, the monomeric phenolic profiles and antioxidant activities of peel, flesh, pomace, whole fruit and juice were evaluated. The results were compared to those of ‘Fuji’ and ‘Granny Smith’ apples. The high‐acid apple possessing the highest total phenolic and anthocyanin contents among three apple varieties contained the most chlorogenic acid, phloridzin, epicatechin, ferulic acid, catechin, vanillic acid, p‐coumaric acid and caffeic acid. The extraction yields of phenolics (64%) and anthocyanins (89%) from the high‐acid apple to juice were the highest. The high‐acid apple possessing the greatest antioxidant activity had the strongest antihaemolysis activity, indicating that it could be used to produce juice and value‐added ingredient to assist in the prevention of chronic disease.
Cholera toxin enhances interleukin‐17A production in both CD4+ and CD8+ cells via a cAMP/protein kinase A‐mediated interleukin‐17A promoter activation
Authors: Tsai Hsing‐Chuan , Velichko Sharlene , Lee Shanshan , Wu Reen
Published: January 2018

Cholera toxin (CT) is a bacterial component that increases intracellular cAMP levels in host cells and suppresses T‐cell activation. Recently, CT was reported to induce T helper type 17‐skewing dendritic cells and activate interleukin‐17A (IL‐17A) production in CD4+ T cells through a cAMP‐dependent pathway. However, the underlying mechanism by which cAMP regulates IL‐17A production in T cells is not completely defined. In this study, we took advantage of a small molecule protein kinase A (PKA) inhibitor (H89) and different cAMP analogues: a PKA‐specific activator (N6‐benzoyl‐adenosine‐cAMP), an exchange protein activated by cAMP‐specific activator (Rp‐8‐chlorophenylthio‐2′‐O‐methyl cAMP), and a PKA inhibitor (Rp‐8‐bromo‐cAMP), to elucidate the signalling cascade of cAMP in IL‐17A regulation in T cells. We found that CT induced IL‐17A production and IL‐17A promoter activity in activated CD4+ T cells through a cAMP/PKA pathway. Moreover, this regulation was via cAMP‐response element binding protein (CREB) ‐mediated transcriptional activation by using the transfection of an IL‐17A promoter–luciferase reporter construct and CREB small interfering RNA in Jurkat cells. Also, we showed that CREB bound to the CRE motif located at −183 of the IL‐17A promoter in vitro. Most interestingly, not only in CD4+ T cells, CT also enhanced cAMP/PKA‐dependent IL‐17A production and CREB phosphorylation in CD8+ T cells. In conclusion, our data suggest that CT induces an IL‐17A‐dominated immune microenvironment through the cAMP/PKA/CREB signalling pathway. Our study also highlights the potentials of CT and cAMP in modulating T helper type 17 responses in vivo.
Achievement goals influence mastery experience via two paths in digital creativity games among elementary school students
Authors: Yeh Y.‐c. , Lin C.S.
Published: January 2018

Although cultivating creativity is greatly emphasized in elementary school education and that digital games can be a promising tool for improving creativity, little research has been conducted to identify and explore how player‐related factors might influence the learning outcomes of digital creativity games. This study identifies 3 individual traits pertaining to digital creativity game playing and examines how these determinants influence self‐efficacy and mastery experiences of creativity using structural equation modelling. The participants were 275 4th through 6th graders, and the employed method was inventory investigation. The findings reveal that the participants spend a large proportion of time playing digital games after school. Moreover, the results suggest that motivation for achieving both mastery goals and performance goals is crucial to enhancing self‐efficacy and achieving mastery experience in creativity. Additionally, such motivation might enhance mastery experience via two paths: the experience of flow states and the strengthening of self‐determination and self‐efficacy. The findings of this study shed light on the design of digital games for creativity training.
The effects of computerized inquiry‐stage‐dependent argumentation assistance on elementary students' science process and argument construction skills
Authors: Lin C.‐H. , Chiu C.‐H. , Hsu C.‐C. , Wang T.‐I. , Chen C.‐H.
Published: January 2018

This study proposed a computerized inquiry‐stage‐dependent argumentation assistance and investigated whether this can help improve elementary students' performance in science processes and the construction of quality arguments. Various argumentation assistances were developed and incorporated into each stage of scientific inquiry in a computer‐supported scientific inquiry system. A nonequivalent quasi‐experimental design was adopted to evaluate the effectiveness of this approach. Two intact sixth grade classes (N = 55) participated in this study, and each student used a tablet computer to accomplish the designated inquiry activities. One class of students was arranged to use the stage‐dependent argumentation assistance, and the other used a generic text‐based interface. The findings indicate that students who used the stage‐dependent argumentation assistance could acquire significantly better science process and argument construction skills than those using the generic text‐based interface.