bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabarcoding for the parallel identification of several hundred predators and their prey: Application to bat species diet analysis
Authors: Galan Maxime , Pons Jean‐Baptiste , Tournayre Orianne , Pierre Éric , Leuchtmann Maxime , Pontier Dominique , Charbonnel Nathalie
Published: December 2017

Assessing diet variability is of main importance to better understand the biology of bats and design conservation strategies. Although the advent of metabarcoding has facilitated such analyses, this approach does not come without challenges. Biases may occur throughout the whole experiment, from fieldwork to biostatistics, resulting in the detection of false negatives, false positives or low taxonomic resolution. We detail a rigorous metabarcoding approach based on a short COI minibarcode and two‐step PCR protocol enabling the “all at once” taxonomic identification of bats and their arthropod prey for several hundreds of samples. Our study includes faecal pellets collected in France from 357 bats representing 16 species, as well as insect mock communities that mimic bat meals of known composition, negative and positive controls. All samples were analysed using three replicates. We compare the efficiency of DNA extraction methods, and we evaluate the effectiveness of our protocol using identification success, taxonomic resolution, sensitivity and amplification biases. Our parallel identification strategy of predators and prey reduces the risk of mis‐assigning prey to wrong predators and decreases the number of molecular steps. Controls and replicates enable to filter the data and limit the risk of false positives, hence guaranteeing high confidence results for both prey occurrence and bat species identification. We validate 551 COI variants from arthropod including 18 orders, 117 family, 282 genus and 290 species. Our method therefore provides a rapid, resolutive and cost‐effective screening tool for addressing evolutionary ecological issues or developing “chirosurveillance” and conservation strategies.
Overexpression of miR‐22 attenuates oxidative stress injury in diabetic cardiomyopathy via Sirt 1
Authors: Tang Qinghui , Len Qiang , Liu Zheng , Wang WeiDong
Published: December 2017

Background/Aims

Oxidative stress injury is believed to be important in diabetic cardiomyopathy. Recent evidence indicates that miR‐22 plays an important role in various cardiovascular diseases, but the protective role of miR‐22 in diabetic cardiomyopathy remains undetermined.

Methods

Diabetes was induced in male C57BL/6 mice by intraperitoneal injection with streptozotocin combined with a high‐fat diet, and miR‐22 was overexpressed following transfection with adeno‐associated virus. Cardiac function was assessed by echocardiography and a cardiac catheter system. In vitro study, H9c2 cells were treated with normal or high glucose (HG), and cell viability or apoptosis was detected using the Cell Counting Kit‐8 (CCK‐8) assay and flow cytometry, respectively. Reactive oxygen species, malondialdehyde, and superoxide dismutase were also detected in diabetic mice and H9c2 cells. The expression level of miR‐22 was detected by real‐time PCR. The protein expression of Sirt 1, oxidative stress injury‐related proteins (GRP78, CHOP, ATF 3), and apoptosis‐related proteins Bax/Bcl‐2, cl‐casp‐9/casp‐9, and cl‐casp‐3/casp‐3 were determined by Western blotting analysis.

Results

HG‐induced oxidative stress injury and apoptosis were observed in H9c2 cells, which were ameliorated by miR‐22. Cardiac dysfunction and severely altered heart structure were also observed in diabetic mice and were dramatically reversed by overexpression of miR‐22. The expression of Sirt 1 decreased significantly in diabetic mice and HG‐treated H9c2 cells. Overexpression of miR‐22 restored the level of Sirt 1. Bioinformatics analysis predicted that Sirt 1 was a potential target gene of miR‐22. Luciferase reporter assay verified that miR‐22 promoted Sirt 1 expression by direct binding to the Sirt 1 3′untranslated repeats. Upregulation of Sirt 1 could improve cell viability and attenuate oxidative stress injury and apoptosis in the HG‐treated H9c2 cells, similar to the effect of miR‐22. However, the protective effects of miR‐22 against HG‐induced oxidative stress injury and apoptosis were abrogated by knockdown of Sirt 1.

Conclusions

Overexpression of miR‐22 can attenuate oxidative stress injury in diabetic cardiomyopathy by upregulation of Sirt 1 in vivo and in vitro.
The Effects of Multitasking on Auditors’ Judgment Quality
Authors: Mullis Curtis E. , Hatfield Richard C.
Published: December 2017

Auditors must frequently multitask in order to complete their work efficiently. However, the potential impact of multitasking on auditors’ judgment quality is poorly understood. Using Ego Depletion Theory and a laboratory experiment, we predict and find that auditors become less able to identify seeded errors after multitasking, and that this effect is most prominent in the identification of conceptual, rather than mechanical, errors. These negative consequences of multitasking are mitigated when auditors are exposed to an intervention based on a theoretical countermeasure of replenishing depleted self‐control resources, in that multitasking auditors identify more seeded errors with the intervention than without. Given that multitasking is a pervasive feature of the current audit environment, these findings have direct implications for audit practice. Beyond identifying multitasking as a cause of impaired performance in auditing, this study's results provide initial evidence that such negative effects can be mitigated, resulting in improved audit quality and, by extension, improved financial statement quality.
Risk factors and peripheral biomarkers for schizophrenia spectrum disorders: an umbrella review of meta‐analyses
Authors: Belbasis L. , Köhler C. A. , Stefanis N. , Stubbs B. , van Os J. , Vieta E. , Seeman M. V. , Arango C. , Carvalho A. F. , Evangelou E.
Published: December 2017

Objective

This study aimed to systematically appraise the meta‐analyses of observational studies on risk factors and peripheral biomarkers for schizophrenia spectrum disorders.

Methods

We conducted an umbrella review to capture all meta‐analyses and Mendelian randomization studies that examined associations between non‐genetic risk factors and schizophrenia spectrum disorders. For each eligible meta‐analysis, we estimated the summary effect size estimate, its 95% confidence and prediction intervals and the I2 metric. Additionally, evidence for small‐study effects and excess significance bias was assessed.

Results

Overall, we found 41 eligible papers including 98 associations. Sixty‐two associations had a nominally significant (P‐value <0.05) effect. Seventy‐two of the associations exhibited large or very large between‐study heterogeneity, while 13 associations had evidence for small‐study effects. Excess significance bias was found in 18 associations. Only five factors (childhood adversities, cannabis use, history of obstetric complications, stressful events during adulthood, and serum folate level) showed robust evidence.

Conclusion

Despite identifying 98 associations, there is only robust evidence to suggest that cannabis use, exposure to stressful events during childhood and adulthood, history of obstetric complications, and low serum folate level confer a higher risk for developing schizophrenia spectrum disorders. The evidence on peripheral biomarkers for schizophrenia spectrum disorders remains limited.
Cancer immunotherapy: A need for peripheral immunodynamic monitoring
Authors: Wang Wenjun , Xia Xiaojun , Wu Sipei , Guo Minzhang , Lie Puyi , He Jianxing
Published: December 2017

Immunotherapy has become an important approach for treating different tumours which has shown significant efficacy in numerous clinical trials, especially those using new checkpoint inhibitors and adoptive cell therapy, which have rapidly become widespread after being approved. However, analysis of peripheral immune biomarkers before and after immunotherapy and their relationship to clinical responses and disease prognosis have rarely been performed in clinical trials. In this review, we examine dynamic changes in the immune system before and after therapy by analyzing recent clinical trials of immunotherapy in patients with cancer that focused on checkpoint inhibitors and adoptive cell therapy. Our aim was to identify circulating biomarkers which can specifically predict clinical response and prognosis, as well as toxicities of immunotherapy. Through this approach, we hope to advance our understanding of the mechanisms of immunotherapy with the goal of developing individualized treatment for cancer patients.
Effects of intrauterine perfusion of human chorionic gonadotropin in women with different implantation failure numbers
Authors: Huang Pinxiu , Wei Lihong , Li Xinlin , Qin Aiping
Published: December 2017

Problem

The aim of this research was to investigate the effects of the intrauterine perfusion of hCG before a frozen‐thawed embryo transfer (FET) in women with different implantation failure numbers.

Method of Study

This was a retrospective analysis of patients undergoing FET who received an intrauterine injection hCG 1000 IU before embryo transfer. The groups included women with their first implantation failure (A group, n = 26), second implantation failure (B group, n = 122), and three or more failures (C group, n = 77). Corresponding control groups (no infusion) were also included. The pregnancy rates were compared among these groups.

Results

After intrauterine injection hCG, the biochemical pregnancy rates were 92.30%, 63.11%, 49.02%, and the clinical pregnancy rates were 76.92%, 54.91%, 48.05%, in the A, B, and C groups, respectively. The biochemical and clinical pregnancy rates were significantly higher in the A group than in the other groups (P < .05). The clinical pregnancy rates of the A and C groups were significantly higher than in the corresponding (no infusion) control groups (76.92% vs 56.81% and 48.05% vs 33.33%, P < .05).

Conclusion

Pregnancy rates decreased with the number of transplant failures. The intrauterine administration of hCG before FET significantly improved the pregnancy rates, especially after one and three or more implantation failures.
Waterbirth in Sweden – a comparative study
Authors: Ulfsdottir Hanna , Saltvedt Sissel , Georgsson Susanne
Published: December 2017

Introduction

The literature describes advantages for mothers giving birth in water, but waterbirth is controversial in Sweden and has not been offered at hospitals until recently. This study aimed to describe and compare the characteristics and outcome of waterbirths with those of spontaneous vaginal births at the same clinics.

Material and methods

A retrospective cohort study was conducted on all waterbirths at two maternity units in Sweden from March 2014 to November 2015 (n = 306), and a consecutively selected comparison group of 306 women having conventional spontaneous vaginal births. Logistic regression was used to analyze the primary outcome; second‐degree perineal tears.

Results

Women giving birth in water had a lower risk of second‐degree perineal tears [adjusted odds ratio (aOR) 0.6, 95% confidence interval (CI) 0.4–0.9]). Their labor was shorter (6 h 3 min vs. 7 h 52 min) and there were significantly fewer interventions than in the comparison group; amniotomy (13.7 vs. 35.3%), internal cardiotocography (11.1 vs. 56.8%), and augmentation with oxytocin (5.2 vs. 31.3%). There were no differences in Apgar scores or admissions to neonatal intensive care unit. The experience of childbirth, measured with a numeric rating scale, was higher in the waterbirth group indicating a more positive birth experience. Three newborns born in water had an umbilical cord avulsion.

Conclusions

In this low‐risk population, waterbirth is associated with positive effects on perineal tears, the frequency of interventions, the duration of labor and women's birth experience. Midwives handling waterbirth should be aware of the risk of umbilical cord avulsion.
Impaired cognitive ability at 2.5 years predicts later visual and ophthalmological problems in children born very preterm
Authors: Hreinsdottir Jonina , Fredriksson Kaul Ylva , Hellström‐Westas Lena , Rosander Kerstin , von Hofsten Claes , Holmström Gerd
Published: December 2017

Aim

To identify possible predictive factors for visual problems at 6.5 years in children born very preterm.

Methods

During 2004–2007, all very preterm infants (gestational age [GA] <32 weeks) in Uppsala County, Sweden were screened for retinopathy of prematurity (ROP) neonatally; at four months, visual tracking was tested; at 2.5 years, visuospatial and cognitive tests were carried out. At 6.5 years, 84 preterm children and a reference group of 64 full‐term children underwent ophthalmological testing.

Results

Mean visual acuity (VA) did not differ between the groups, but subnormal VA (≤0.8) was more common in the preterm group (31% vs 14%; p < 0.05). More often than full‐term children, preterm children had impaired contrast sensitivity (<0.5) (36% vs 19%; p < 0.05) and strabismus (8% vs 0%; p < 0.05). Low GA, ROP, intraventricular haemorrhage 3‐4/periventricular leukomalacia and cognitive disability at 2.5 years predicted ophthalmological and visual problems at 6.5 years. Visual tracking ability at four months was not predictive of ophthalmological outcome.

Conclusion

Children born preterm had more ophthalmological problems at 6.5 years of age, including subtle dysfunctions. ROP, early brain injury and impaired cognitive function around 2.5 years predicted later ophthalmological dysfunctions.
Advances in specification testing
Authors: Davidson Russell , Zinde‐Walsh Victoria
Published: December 2017

Testing the specification of econometric models has come a long way from thettests andFtests of the classical normal linear model. In this paper, we trace the broad outlines of the development of specification testing, along the way discussing the role of structural versus purely statistical models. Inferential procedures have had to advance in tandem with techniques of estimation, and so we discuss the generalized method of moments, non parametric inference, empirical likelihood and estimating functions. Mention is made of some recent literature, in particular, of weak instruments, non parametric identification and the bootstrap.
Expansion of human γδ T cells for adoptive immunotherapy using a bisphosphonate prodrug
Authors: Tanaka Yoshimasa , Murata‐Hirai Kaoru , Iwasaki Masashi , Matsumoto Kenji , Hayashi Kosuke , Kumagai Asuka , Nada Mohanad H. , Wang Hong , Kobayashi Hirohito , Kamitakahara Hiroshi , Okamura Haruki , Sugie Tomoharu , Minato Nagahiro , Toi Masakazu , Morita Craig T.
Published: December 2017

Cancer immunotherapy with human γδ T cells expressing Vγ2Vδ2 T cell receptor (also termed Vγ9Vδ2) has shown promise because of their ability to recognize and kill most types of tumors in a major histocombatibility complex (MHC) ‐unrestricted fashion that is independent of the number of tumor mutations. In clinical trials, adoptive transfer of Vγ2Vδ2 T cells has been shown to be safe and does not require preconditioning. In this report, we describe a method for preparing highly enriched human Vγ2Vδ2 T cells using the bisphosphonate prodrug, tetrakis‐pivaloyloxymethyl 2‐(thiazole‐2‐ylamino)ethylidene‐1,1‐bisphosphonate (PTA). PTA stimulated the expansion of Vγ2Vδ2 cells to purities up to 99%. These levels were consistently higher than those observed after expansion with zoledronic acid, the most commonly used stimulator for clinical trials. Cell numbers also averaged more than those obtained with zoledronic acid and the expanded Vγ2Vδ2 cells exhibited high cytotoxicity against tumor cells. The high purity of Vγ2Vδ2 cells expanded by PTA increased engraftment success in immunodeficient NOG mice. Even low levels of contaminating αβ T cells resulted in some mice with circulating human αβ T cells rather than Vγ2Vδ2 cells. Vγ2Vδ2 cells from engrafted NOG mice upregulated CD25 and secreted tumor necrosis factor‐α and interferon‐γ in response to PTA‐treated tumor cells. Thus, PTA expands Vγ2Vδ2 T cells to higher purity than zoledronic acid. The high purities allow the successful engraftment of immunodeficient mice without further purification and may speed up the development of allogeneic Vγ2Vδ2 T cell therapies derived from HLA‐matched normal donors for patients with poor autologous Vγ2Vδ2 T cell responses.
Third‐generation oncolytic herpes simplex virus inhibits the growth of liver tumors in mice
Authors: Nakatake Richi , Kaibori Masaki , Nakamura Yusuke , Tanaka Yoshito , Matushima Hideyuki , Okumura Tadayoshi , Murakami Takashi , Ino Yasushi , Todo Tomoki , Kon Masanori
Published: December 2017

Multimodality therapies are used to manage patients with hepatocellular carcinoma (HCC), although advanced HCC is incurable. Oncolytic virus therapy is probably the next major breakthrough in cancer treatment. The third‐generation oncolytic herpes simplex virus type 1 (HSV‐1) T‐01 kills tumor cells without damaging the surrounding normal tissues. Here we investigated the antitumor effects of T‐01 on HCC and the host's immune response to HCC cells. The cytopathic activities of T‐01 were tested in 14 human and 1 murine hepatoma cell line in vitro. In various mouse xenograft models, HuH‐7, KYN‐2, PLC/PRF/5 and HepG2 human cells and Hepa1‐6 murine cells were used to investigate the in vivo efficacy of T‐01. T‐01 was cytotoxic to 13 cell lines (in vitro). In mouse xenograft models of subcutaneous, orthotopic and peritoneal tumor metastasis in athymic mice (BALB/c nu/nu), the growth of tumors formed by the human HCC cell lines and hepatoblastoma cell line was inhibited by T‐01 compared with that of mock‐inoculated tumors. In a bilateral Hepa1‐6 subcutaneous tumor model in C57BL/6 mice, the growth of tumors inoculated with T‐01 was inhibited, as was the case for contralateral tumors. T‐01 also significantly reduced tumor growth. T‐01 infection significantly enhanced antitumor efficacy via T cell‐mediated immune responses. Results demonstrate that a third‐generation oncolytic HSV‐1 may serve as a novel treatment for patients with HCC.
C‐C motif ligand 5 promotes migration of prostate cancer cells in the prostate cancer bone metastasis microenvironment
Authors: Urata Satoko , Izumi Kouji , Hiratsuka Kaoru , Maolake Aerken , Natsagdorj Ariunbold , Shigehara Kazuyoshi , Iwamoto Hiroaki , Kadomoto Suguru , Makino Tomoyuki , Naito Renato , Kadono Yoshifumi , Lin Wen‐Jye , Wufuer Guzailinuer , Narimoto Kazutaka , Mizokami Atsushi
Published: December 2017

Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co‐cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration‐dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C‐C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling.
Cdc37 facilitates cell survival of colorectal carcinoma via activating the CDK4 signaling pathway
Authors: Zhu Jianjun , Yan Fang , Tao Jia , Zhu Xiaohua , Liu Jiayou , Deng Shishan , Zhang Xiaoming
Published: December 2017

Cell division cycle 37 (Cdc37) is an important partner for heat shock protein 90 (HSP90), assisting in molecular chaperone activities, particularly with regard to the regulation of protein kinases. Given its influence on cell growth pathways, Cdc37 has been discussed as a potential intermediate in carcinogenesis. However, to date, the potential functional roles and molecular mechanisms by which Cdc37 regulates cell survival in colorectal carcinoma (CRC) remain unclear. Here, we investigated the expression of Cdc37 and its clinical significance in CRC, and systematically explored the role and the underlying mechanism of Cdc37 in CRC cell survival both in vitro and in vivo. Our results showed that Cdc37 was remarkably up‐regulated in CRC, which facilitated cell survival mainly by promoting cell proliferation, G1‐S transition, and inhibiting cell apoptosis. Our data further indicated that Cdc37 increased the stability of cyclin‐dependent kinase 4 (CDK4) to activate the retinoblastoma 1 (RB1) signaling pathway, followed by increased expression of Bcl‐2 and Bcl‐xL, which ultimately promoted cell survival in CRC. Moreover, knockdown of CDK4 reversed the Cdc37‐mediated effect in promoting the progression of CRC. Our findings showed that Cdc37 played a critical role in promoting CRC cell survival by increasing CDK4 stability to activate the RB1 signaling pathway. Thereby, Cdc37 might serve as a potential therapeutic target in CRC patients.
Dietary acrylamide intake and risk of breast cancer: The Japan Public Health Center‐based Prospective Study
Authors: Kotemori Ayaka , Ishihara Junko , Zha Ling , Liu Rong , Sawada Norie , Iwasaki Motoki , Sobue Tomotaka , Tsugane Shoichiro ,   the JPHC Study Group
Published: December 2017

Acrylamide forms during cooking and is classified as a probable carcinogen in humans, mandating the need for epidemiological studies of dietary acrylamide and cancers. However, the risk of dietary acrylamide exposure to breast cancer in Japanese women has not been assessed. We investigated the association between dietary acrylamide intake and risk of breast cancer in the Japan Public Health Center‐based Prospective Study. The present study included 48 910 women aged 45‐74 years who responded to a 5‐year follow‐up survey questionnaire. Dietary acrylamide intake was assessed using a validated food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. During an average of 15.4 years of follow up, 792 breast cancers were diagnosed. Energy‐adjusted dietary acrylamide intake was not associated with the risk of breast cancer (adjusted hazard ratio for highest versus lowest tertile = .95, 95% confidence intervals: 0.79‐1.14, P‐trend = .58). Further, no significant associations were observed when stratified analyses were conducted by smoking status, coffee consumption, alcohol consumption, body mass index, menopausal status, estrogen receptor status, and progesterone receptor status. In conclusion, dietary acrylamide intake was not associated with the risk of breast cancer in this population‐based prospective cohort study of Japanese women.
Pretreatment with probiotic Bifico ameliorates colitis‐associated cancer in mice: Transcriptome and gut flora profiling
Authors: Song Huan , Wang Weiyi , Shen Bo , Jia Hao , Hou Zhaoyuan , Chen Ping , Sun Yunwei
Published: December 2017

Individuals with inflammatory bowel disease are at high risk of developing colitis‐associated cancer (CAC). Strategies to block the process from inflammatory bowel disease to CAC should be considered. In the experiment, we aim to explore the chemopreventive efficacy of the probiotic cocktail Bifico and its potential mechanism in azoxymethane and dextran sodium sulphate‐induced CAC in mice. Oral pretreatment of Bifico was adopted to evaluate its protective effect. The colorectums of 35 C57BL/6 mice were collected and examined for the degree of inflammation and tumorigenesis. Comparative 16S rRNA sequencing was carried out to observe Bifico‐target alterations in gene expression and microbiota structure. We found that pretreatment of Bifico alleviated intestinal inflammation and reduced tumor formation. Furthermore, we identified a subset of genes as potential targets of Bifico treatment, including CXCL1, CXCL2, CXCL3, and CXCL5, which are all ligands of C‐X‐C motif receptor 2 (CXCR2). The 16S rRNA sequencing showed that Bifico decreased the abundance of genera Desulfovibrio, Mucispirillum, and Odoribacter, and a bloom of genus Lactobacillus was detected. Notably, we found that an abundance of these Bifico‐target taxa was significantly associated with the expression of CXCR2 ligand genes. Our studies indicate that Bifico, given orally, can ameliorate CAC in mice through intervening with the possible link between Desulfovibrio, Mucispirillum, Odoribacter, Lactobacillus, and CXCR2 signaling.
Immunopharmacogenomics towards personalized cancer immunotherapy targeting neoantigens
Authors: Kiyotani Kazuma , Chan Hiu Ting , Nakamura Yusuke
Published: December 2017

Utilizing the host immune system to eradicate cancer cells has been the most investigated subject in the cancer research field in recent years. However, most of the studies have focused on highly variable responses from immunotherapies such as immune checkpoint inhibitors, from which the majority of patients experienced no or minimum clinical benefit. Advances in genomic sequencing technologies have improved our understanding of immunopharmacogenomics and allowed us to identify novel cancer‐specific immune targets. Highly tumor‐specific antigens, neoantigens, are generated by somatic mutations that are not present in normal cells. It is plausible that by targeting antigens with high tumor‐specificity, such as neoantigens, the likelihood of toxic effects is very limited. However, understanding the interaction between neoantigens and the host immune system remains a significant challenge. This review focuses on the potential use of neoantigen‐targeted immunotherapies in cancer treatment and the recent progress of different strategies in predicting, identifying, and validating neoantigens. Successful identification of highly tumor‐specific antigens accelerates the development of personalized immunotherapy with no or minimum adverse effects and with a broader coverage of patients.
Type III interferons are critical host factors that determine susceptibility to Influenza A viral infection in allergic nasal mucosa
Authors: Jeon Y. J. , Lim J. H. , An S. , Jo A. , Han D. H. , Won T.‐B. , Kim D.‐Y. , Rhee C.‐S. , Kim H. J.
Published: December 2017

Background

Allergic respiratory conditions have been associated with increased susceptibility to viral infection due to impaired interferon (IFN)‐related immune responses, but the mechanisms for reinforcement of mucosal immunity against viral infection in allergic diseases are largely unknown.

Objectives

To determine whether IFN induction would be impaired in allergic nasal mucosa and to identify whether higher loads of influenza A virus (IAV) in allergic nasal mucosa could be controlled with IFN treatment.

Methods

Influenza A virus mRNA, viral titres and IFN expression were compared in IAV‐infected normal human nasal epithelial (NHNE, N = 10) and allergic rhinitis nasal epithelial (ARNE, N = 10) cells. We used in vivo model of allergic rhinitis (BALB/c mice, N = 10) and human nasal mucosa from healthy volunteers (N = 72) and allergic rhinitis patients (N = 29) to assess the induction of IFNs after IAV infection.

Results

Influenza A virus mRNA levels and viral titres were significantly higher in ARNE compared with NHNE cells. IFN‐β and IFN‐λs were induced in NHNE and ARNE cells up to 3 days after IAV infection. Interestingly, induction of IFN‐λs mRNA levels and the amount of secreted proteins were considerably lower in ARNE cells. The mean IFN‐λs mRNA level was also significantly lower in the nasal mucosa of AR patients, and we found that recombinant IFN‐λ treatment attenuated viral mRNA levels and viral titres in IAV‐infected ARNE cells. In vivoAR mouse exhibited higher viral load after IAV infection, but intranasal inoculation of IFN‐λ completely decreased IAV protein expression and viral titre in nasal mucosa of IAV‐infected AR mouse.

Conclusion

Higher susceptibility of the allergic nasal mucosa to IAV may depend on impairment of type III IFN induction, and type III IFN is a key mechanistic link between higher viral loads and control of IAV infection in allergic nasal mucosa.
Optimal iodine supplementation during antithyroid drug therapy for Graves’ disease is associated with lower recurrence rates than iodine restriction
Authors: Huang Huibin , Shi Yaxiong , Liang Bo , Cai Huiyao , Cai Qingyan , Lin Ruhai
Published: December 2017

Objective

A relationship between iodine intake and the effectiveness of antithyroid drug (ATD) therapy for Graves’ disease (GD) has been suggested, and strict restriction of iodine intake has been tried in the treatment of GD in some studies. However, it is unclear whether dietary iodine supplementation improves the prognosis of ATD therapy for GD. This study aimed to clarify whether optimal iodine supplementation during antithyroid drug therapy for GD is associated with lower recurrence rates than iodine restriction.

Methods

This was a prospective randomized trial of newly diagnosed patients with GD. Patients with newly diagnosed GD were recruited. After ATD therapy and strict dietary iodine restriction for 1 month, patients (n = 459) were randomly assigned to iodine‐supplemented and iodine‐restricted groups. After exclusion, 405 patients finally completed the study. The iodine‐supplemented group included 203 patients (61 males and 142 females) with an average age of 32.2 ± 10.5 years (17‐65 years), and the iodine‐restricted group included 202 patients (61 males and 141 females) with an average age of 31.9 ± 11.8 years (16‐64 years). Patients in the iodine‐supplemented group were given about 10 grams of iodized salt every day, while the iodine‐restricted group received noniodized salt with low‐iodine or noniodine diet. The dietary iodine intervention lasted for 24 months. Urinary iodine concentration (UIC), thyrotropin receptor antibody (TRAb), free T3 (FT3), free T4 (FT4) and thyrotropin (TSH) of 2 groups were measured every 3 months. The recurrence rates within 12 months after withdrawal of ATD were evaluated.

Results

UIC in the iodine‐supplemented group was within the recommended range for optimal iodine intake (135‐162 μg/L) and was significantly higher than that in iodine‐restricted group (30‐58 μg/L). Within 12 months of withdrawal of ATD, the total recurrence rate in the iodine‐supplemented group was 35.5%, significantly lower than in the iodine‐restricted group, which was 45.5%.

Conclusion

Optimal dietary iodine supplementation during antithyroid drug therapy for GD is associated with lower recurrence rates than iodine restriction, and therefore, diet control with strict iodine restriction might be an adverse factor in the management of GD.
Bone response to functionally loaded, two‐piece zirconia implants: A preclinical histometric study
Authors: Janner Simone F. M. , Gahlert Michael , Bosshardt Dieter D. , Roehling Stefan , Milz Stefan , Higginbottom Frank , Buser Daniel , Cochran David L.
Published: December 2017

Objective

To evaluate the bone response to a two‐piece zirconia implant in comparison with a control titanium implant in the canine mandible 4 and 16 weeks after restoration.

Material and Methods

Zirconia and titanium implants were alternately placed bilaterally in healed mandibular molar and premolar sites of five canines. Full‐ceramic single‐tooth restorations were cemented after 6 weeks of transmucosal healing, allowing for full functional loading of the implants. Histologic and histometric analyses were performed on orofacial and mesiodistal undecalcified sections of the specimens obtained upon sacrifice after 4 and 16 weeks of functional loading. Bone‐to‐implant contact (BIC), multinucleated giant cells‐to‐implant contact (MIC), crestal bone level, and peri‐implant bone density were histometrically assessed.

Results

All 60 implants and 60 restorations were still in function after 4 and 16 weeks of loading in both test and control groups. No implant loss, no implant or abutment fracture, and no chipping of the restorations could be detected. Histometric analysis showed no statistically significant differences between zirconia and titanium implants in BIC, crestal bone level, and peri‐implant bone density at both time points. Between 4 and 16 weeks, the crestal bone level around zirconia implants showed a small but statistically significant increase in its distance from the implant shoulder. MIC was very low on both implant types and both time points and decreased statistically significantly overtime.

Conclusion

The present two‐piece zirconia implant showed a similar bone integration compared to the titanium implant with similar surface morphology after 4 and 16 weeks of loading.
Multivisceral transplant is a viable treatment option for patients with non‐resectable intra‐abdominal fibromatosis
Authors: Chi Zhikai , Mangus Richard S , Kubal Chandrashekhar A. , Chen Shaoxiong , Lin Jingmei
Published: December 2017

Background

Intra‐abdominal fibromatosis often involves the mesentery root which is non‐resectable by conventional surgery. Multivisceral transplant (MVT), as a potential cure to non‐resectable fibromatosis, has rarely been reported and the prognosis is unknown.

Methods

Six patients who underwent MVT for intra‐abdominal fibromatosis were reviewed. Clinicopathological features, immunohistochemistry for β‐catenin, p53, and Ki67, and outcomes were evaluated. Appropriate data for comparative analysis were obtained from a cohort of 24 patients who underwent conventional resection for intra‐abdominal fibromatosis.

Results

Among six MVT patients, four had familial adenomatous polyposis (FAP). Two patients had an initial intestinal transplantation, three had multiple prior surgeries, and two had adjuvant therapy. One patient died of hemorrhagic stroke shortly after MVT, and five patients (83%) survived with a median follow‐up of 64 months. The 1‐year and 5‐year survival rates were 67% for all five patients. Two patients had recurrences after MVT and one of them had FAP. In comparison, six of 24 patients who underwent conventional surgery had FAP; six (25%) had recurrences and three had FAP. For FAP patients; the mean recurrence time was 13 months for MVT versus 6 months for conventional surgery. Ki67 proliferative index, β‐catenin, and p53 expression did not significantly correlate to recurrence.

Conclusions

Multivisceral transplant (MVT) is a viable option for patients who have non‐resectable intra‐abdominal fibromatosis with promising surviving rates, although recurrence still occurs. Surgical margin, Ki67 proliferative index, β‐catenin, and p53 expression are not predicative for recurrence of fibromatosis.
Usefulness of argon plasma coagulation ablation subsequent to endoscopic snare papillectomy for ampullary adenoma
Authors: Nam Kwangwoo , Song Tae Jun , Kim Raymond E. , Cho Dong Hui , Cho Min Keun , Oh Dongwook , Park Do Hyun , Lee Sang Soo , Seo Dong‐Wan , Lee Sung Koo , Kim Myung‐Hwan , Baek Seunghee
Published: December 2017

Background and Aim

Endoscopic snare papillectomy (ESP) is an effective treatment for ampullary adenoma. Argon plasma coagulation (APC) is widely used as an additional method to control bleeding or ablate the residual tumor. However, the efficacy of this procedure has not yet been fully evaluated. This study aimed to evaluate the usefulness of APC as an additional method to ESP.

Methods

Patients who underwent ESP for ampullary adenoma between September 2005 and September 2015 were retrospectively reviewed. Using propensity score matching, we compared short‐ and long‐term outcomes between the ESP‐with‐additional‐APC group (ESP + APC group) and the ESP‐only group. Primary outcome was early post‐ESP adverse events (AE), and secondary outcomes were late AE and recurrence.

Results

Among 109 patients, additional APC was carried out in 59 (54.1%) patients. After matching, 41 patients were included in both groups, respectively. Bleeding rate was significantly lower in the ESP + APC group than in the ESP‐only group (7.3% vs 31.7%, odds ratio = 0.180, P < 0.01). However, there were no significant differences in other procedure‐related early AE such as pancreatitis (12.2% vs 19.5%, P = 0.365), cholangitis (2.4% vs 9.8%, P = 0.198), and perforation (2.4% vs 2.4%, P = 1.000) between the ESP + APC group and the ESP‐only group. During the follow‐up period (mean 904 ± 868 days), papillary stricture (9.8% vs 4.9%, P = 0.405) and recurrence rates (24.4% vs 24.4%, P = 0.797) were not significantly different between the ESP + APC group and the ESP‐only group.

Conclusion

Additional APC during ESP may have a beneficial effect by decreasing bleeding rate without harmful effects.
‘Leukodystrophy‐like’ phenotype in children with myelin oligodendrocyte glycoprotein antibody‐associated disease
Authors: Hacohen Yael , Rossor Thomas , Mankad Kshitij , Chong Wk ‘Kling’ , Lux Andrew , Wassmer Evangeline , Lim Ming , Barkhof Frederik , Ciccarelli Olga , Hemingway Cheryl
Published: December 2017

Aim

To review the demographics and clinical and paraclinical parameters of children with myelin oligodendrocyte glycoprotein (MOG) antibody‐associated relapsing disease.

Method

In this UK‐based, multicentre study, 31 children with MOG antibody‐associated relapsing disease were studied retrospectively.

Results

Of the 31 children studied, 14 presented with acute disseminated encephalomyelitis (ADEM); they were younger (mean 4.1y) than the remainder (mean 8.5y) who presented with optic neuritis and/or transverse myelitis (p<0.001). Similarly, children who had an abnormal brain magnetic resonance imaging (MRI) at onset (n=20) were younger than patients with normal MRI at onset (p=0.001) or at follow‐up (p<0.001). ‘Leukodystrophy‐like’ MRI patterns of confluent largely symmetrical lesions was seen during the course of the disease in 7 out of 14 children with a diagnosis of ADEM, and was only seen in children younger than 7 years of age. Their disability after a 3‐year follow‐up was mild to moderate, and most patients continued to relapse, despite disease‐modifying treatments.

Interpretation

MOG antibody should be tested in children presenting with relapsing neurological disorders associated with confluent, bilateral white matter changes, and distinct enhancement pattern. Children with MOG antibody‐associated disease present with age‐related differences in phenotypes, with a severe leukoencephalopathy phenotype in the very young and normal intracranial MRI in the older children. This finding suggests a susceptibility of the very young and myelinating brain to MOG antibody‐mediated mechanisms of damage.

What this paper adds

Myelin oligodendrocyte glycoprotein (MOG) antibody‐associated demyelination manifest with an age‐related phenotype.

Children with MOG antibody and ‘leukodystrophy‐like’ imaging patterns tend to have poor response to second‐line immunotherapy.
The types and management of dental trauma during military service in Finland
Authors: Antikainen Atte , Patinen Pertti , Päkkilä Jari , Tjäderhane Leo , Anttonen Vuokko
Published: December 2017

Background/Aims

All Finnish males must attend compulsory military service that lasts from 6 months to 1 year. About 25 000 males (approximately 80% of each age cohort) and 400 volunteer females complete the service annually. The aim of the study was to investigate the types of dental trauma occurring among Finnish conscripts during their military service. The article also focused on how dental trauma is treated in the Finnish Defence Forces.

Material and Methods

All dental records in the Defence Forces’ patient register concerning dental trauma during the years 2011 and 2012 were analysed by tooth number, treatment procedures and number of visits.

Results

According to the patient register, 361 conscripts suffered an oral trauma during their military service; thus, the average annual incidence was 7.2 trauma per 1000 conscripts. A total of 483 teeth were traumatized in the 2‐year period. The most frequently traumatized teeth were the maxillary central incisors (61%), and the most common findings were enamel or enamel‐dentin fractures (63% of all findings). Severe trauma was not common, and the most severe ones occurred during off‐duty hours. The most common treatment was direct filling (n = 189 patients). Only 53 patients had soft tissue injuries (bruises, wounds). Among patients with dental trauma, the mean number of visits to the Defence Forces’ dental clinic was 1.9. Great variation exists in recording findings concerning dental and oral trauma.

Conclusion

Minor trauma is common. In all cases, recording trauma and treatments should be performed carefully.
Indigenous cultural competence: A dental faculty curriculum review
Authors: Forsyth C. , Irving M. , Tennant M. , Short S. , Gilroy J.
Published: December 2017

Background

Indigenous Australians have more than double the rate of poor oral health than their non‐Indigenous counterparts. Cultural competence of dental and oral health practitioners is fundamental to health care and quality of life in addressing health disparities in minority cultural groups in Australia. Higher education curricula reviews have identified the need for institutions to incorporate Indigenous culture and knowledge more widely into the curricula to improve educational outcomes for Indigenous Australians and to increase cultural competence for all students.

Aim

The aim of this research was to provide a baseline analysis of Indigenous cultural competence curricula practices to ascertain changes required within Faculty of Dentistry programmes at the University of Sydney to enable students to become more culturally competent upon graduation.

Methods

Staff and students of the Doctor of Dental Medicine and Bachelor of Oral Health programmes at the Faculty of Dentistry, University of Sydney participated in an online survey. Quantitative analysis of the survey data was conducted using integrated research electronic data capture survey tools, with open‐ended questions being coded to common responses for those questions.

Results

A total of 69 staff (71%) and 191 students (51%) participated in the online survey. The majority of participants perceived there was limited Indigenous content in the curriculum. Most participants reported that Indigenous curriculum was integrated into several units of study. The main pedagogical method for curriculum delivery was lectures, followed by case studies and group discussions.

Conclusion

Although some Indigenous content exists in dental faculty curriculum, in‐depth investigation is required to develop a comprehensive, evidenced‐based Indigenous cultural competence teaching framework, for integration into Doctor of Dental Medicine and Bachelor of Oral Health curricula.
Evaluation of an animation tool developed to supplement dental student study of the cranial nerves
Authors: Lone M. , McKenna J. P. , Cryan J. F. , Vagg T. , Toulouse A. , Downer E. J.
Published: December 2017

Introduction

The structure/function of the cranial nerves is a core topic for dental students. However, due to the perceived complexity of the subject, it is often difficult for students to develop a comprehensive understanding of key concepts using textbooks and models. It is accepted that the acquisition of anatomical knowledge can be facilitated by visualisation of structures. This study aimed to develop and assess a novel cranial nerve animation as a supplemental learning aid for dental students.

Materials and Methods

A multidisciplinary team of anatomists, neuroscientists and a computer scientist developed a novel animation depicting the cranial nerves. The animation was viewed by newly enrolled first‐year dental students, graduate entry dental students (year 1) and dental hygiene students (year 1). A simple life scenario employing the use of the cranial nerves was developed using a cartoon‐type animation with a viewing time of 3.58 minutes. The animation was developed with emphasis on a life scenario. The animation was placed online for 2 weeks with open access or viewed once in a controlled laboratory setting. Questionnaires were designed to assess the participants’ attitude towards the animation and their knowledge of the cranial nerves before and after visualisation. This study was performed before the delivery of core lectures on the cranial nerves.

Results

Our findings indicate that the use of the animation can act as a supplemental tool to improve student knowledge of the cranial nerves. Indeed, data indicate that a single viewing of the animation, in addition to 2‐week access to the animation, can act as a supplemental learning tool to assist student understanding of the structure and function of cranial nerves. The animation significantly enhanced the student's opinion that their cranial nerve knowledge had improved. From a qualitative point of view, the students described the animation as an enjoyable and useful supplement to reading material/lectures and indicated that the animation was a useful tool in understanding the cranial nerves.

Conclusion

Overall, these findings indicate that an animation demonstrating the cranial nerves in a simple, everyday functional scenario may act as a learning aid in the study of cranial nerves.
Omitting cytogenetic assessment from routine treatment response monitoring in chronic myeloid leukemia is safe
Authors: Geelen Inge G.P. , Thielen Noortje , Janssen Jeroen J.W.M. , Hoogendoorn Mels , Roosma Tanja J.A. , Valk Peter J.M. , Visser Otto , Cornelissen Jan J. , Westerweel Peter E.
Published: December 2017

Objectives

The monitoring of response in chronic myeloid leukemia (CML) is of great importance to identify patients failing their treatment in order to adjust TKI choice and thereby prevent progression to advanced stage disease. Cytogenetic monitoring has a lower sensitivity, is expensive, and requires invasive bone marrow sampling. Nevertheless, chronic myeloid leukemia guidelines continue to recommend performing routine cytogenetic response assessments, even when adequate molecular diagnostics are available.

Methods

In a population‐based registry of newly diagnosed CML patients in the Netherlands, all simultaneous cytogenetic and molecular assessments performed at 3, 6, and 12 months were identified and response of these matched assessments was classified according to European Leukemia Net (ELN) recommendations. The impact of discrepant cytogenetic and molecular response classifications and course of patients with additional chromosomal abnormalities were evaluated.

Results

The overall agreement of 200 matched assessments was 78%. In case of discordant responses, response at 24 months was consistently better predicted by the molecular outcome. Cytogenetic response assessments provided relevant additional clinical information only in some cases of molecular “warning.” The development of additional cytogenetic abnormalities was always accompanied with molecular failure.

Conclusion

We conclude that it is safe to omit routine cytogenetics for response assessment during treatment and to only use molecular monitoring, in order to prevent ambiguous classifications, reduce costs, and reduce the need for invasive bone marrow sampling. Cytogenetic re‐assessment should still be performed when molecular response is suboptimal.
Insular damage, death and newly diagnosed atrial fibrillation in intracerebral hemorrhage: stroke‐induced heart injury as the potential missing link
Authors: Mai L. M. , Sposato L. A.
Published: December 2017

Click here to view the accompanying paper in this volume.