bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversing the tide of sport globalization from west to east? Examining consumer demand for table tennis clubs in the U.S.
Authors: Zhang Yi , Kim Minkil , Wang Jerred Junqi , Pitts Brenda
Published: March 2018

Purpose

By using table tennis as an example and conducting an in-depth investigation into the impact of market demand factors on membership consumption of table tennis club members in the USA, the purpose of this paper is to illustrate the opportunities and marketing efforts needed for Asian sports to survive and thrive in North America, in which consumer demand factors assessing core program features of table tennis clubs were found to be very influential of cognitive, affective, and behavioral consumptions of table tennis club members.

Design/methodology/approach

Through conducting a review of literature, observations of club operations, and interviews of club administrators and club members representing various table tennis clubs, a preliminary questionnaire was formulated for this study. The initial questionnaire was submitted to a panel of five experts, for a test of content validity. By incorporating their suggestions, editing was made to improve a number of the items in the questionnaire. Data collection took place in two national table tennis tournaments, two local tournaments, and six table tennis clubs. Procedures in SPSS 19.0 (SPSS, 2009) and Mplus 5.21 were carried out for data analyses.

Findings

The findings of this study are that market demand factors would be significantly related to consumer perceived benefits and perceived value, and in turn related to consumer satisfaction of table tennis club membership. The market demand factors had a positive impact on perceived value and benefits confirmed the theoretical framework and previous research findings, which also made a practical sense that a table tennis club needs to offer product features and meet expectations of its current and potential members in order to enhance program value and benefits perceived by its members.

Originality/value

The past two decades have marked the speediest rise of a globalized sport production and consumption trend. In an era of globalized sport marketplace, sports have become a business commodity to meet the needs of commerce. For an Asian sport to penetrate into the North American marketplace as table tennis has done, it would be wise to develop regional network, strategies, product, and promotions. It is expected that table tennis as a popular Asian sport will continue being spread to other parts of the world; thus, the findings of this study have potential relevance to promoting table tennis globally.
A model of fans’ reaction to resurrected brands of sport organizations
Authors: Florea Dorian-Laurentiu , Barbu Catalin Mihail , Barbu Mihai Constantin Razvan
Published: March 2018

Purpose

The purpose of this paper is to reveal the conditions that facilitate or hinder a favorable reaction of fans to the resurrection of sport club brands.

Design/methodology/approach

The proposed model was empirically tested by applying partial least squares-SEM to a sample of 462 fans of five Romanian football and handball clubs that were resurrected in the last five years.

Findings

The study showed that a positive relationship between the new and the old club owners, the keeping of the brand name, and the involvement of the club’s historic figures are favorable conditions for a successful resurrection. The faded brands that enjoy salient heritage and numerous loyal fans are more likely to be successfully resurrected. Moreover, when the resurrection is undertaken immediately after the old club’s bankruptcy, fans tend to alienate from the brand, as they consider the new club to be trying to counterfeit the meaning of the faded brand.

Research limitations/implications

The cross-sectional nature of the study and the narrow scope of the empirical data are the major limitations of the study.

Practical implications

Based on the empirical findings, the authors made recommendations to sport entrepreneurs who consider reviving faded clubs, and highlighted the difficulties of the resurrection process.

Originality/value

To the best of the authors’ knowledge, this is the first study of brand resurrection in the sports industry.
Examining the architecture of leadership coaching
Authors: Cosner Shelby , Walker Lisa , Swanson Jason , Hebert Martha , Whalen Samuel P.
Published: March 2018

Purpose

The purpose of this paper is to identify the coaching structures that aspiring principals associate with developmentally consequential coaching interactions; identify structural features/functions/attributes that shape a structure’s developmental utility and use; and consider how a multifarious coaching structure might advantage the learning experiences of aspiring principals.

Design/methodology/approach

This qualitative study included multiple interviews with two cohorts of aspiring principals (n=20) from one preparation program and with their leadership coaches (n=5) and was framed using the theories of social capital and networks, situated learning, and distributed cognition.

Findings

The authors identified eight coaching structures that aspirants identified as consequential to their learning and development. The authors identified four structural features/functions/attributes that shape a structure’s developmental utility. The authors identified three factors that contribute to the developmental utility of this multifarious coaching model.

Research limitations/implications

This study includes a relatively small participant sample –70 percent of the aspiring principals from two cohorts within one preparation program. Data do not include direct observations of coaching interactions within the context of individual coaching structures.

Practical implications

The findings suggest that the structuring of leadership coaching is a critical consideration for those designing leadership coaching programs. This multifarious structuring of leadership coaching created three developmental affordances.

Originality/value

This paper generates new knowledge for the field of principal preparation related to the structuring of leadership coaching and ways in which structuring can shape aspirant learning experiences. These findings are likely to also be instructive to those interested in coaching more generally.
Assisted living technologies and the consumer market: how is it developing?
Authors: Ward Gillian , Winchcombe Maggie , Teah Grace
Published: March 2018

Purpose

A three-year research study, funded by Innovate UK, Consumer Models for Assisted Living (COMODAL) aimed to support the development of the consumer market for electronic assisted living technology (eALT) products and services, particularly for people aged 50-70, approaching older age and retirement themselves or with caring responsibilities for family or friends. The purpose of the COMODAL study was to gain a greater understanding of their needs and behaviours relating to the acquisition of eALT and develop sustainable consumer-led business models that might address these needs and support business development within a consumer market (Ward et al., 2016). The purpose of this paper is to present a follow up study to explore how the market may have changed since the publication of the research findings.

Design/methodology/approach

An online survey was used to collect both qualitative and quantitative data from individuals working in the supply and distribution of assisted living technologies in the UK regarding how their businesses had developed in the past two years.

Findings

The results showed that since the publication of the COMODAL research there have been changes in the way that the consumer market for eALT is being approached, not only with more direct marketing focused on consumer’s needs but also in direct partnerships with local authorities that offer greater choice with an improved range of products.

Originality/value

This is the first paper in the UK to follow up the impact of the original COMODAL research and explore its influence on the development of the consumer market for eALT.
Telephone consultation in primary care
Authors: Gonzalez Francisco , Cimadevila Blanca , Garcia-Comesaña Julio , Cerqueiro Susana , Andion Eladio , Prado Jorge , Bermudez Jorge , Rubial Felix
Published: March 2018

Purpose

The purpose of this paper is to describe and analyze a teleconsultation modality based on a simple telephone call, using either landline or mobile phone, made available to more than two million people. Telecommunication systems are an increasingly common feature in modern healthcare. However, making teleconsultations available to the entire population covered by a public health system is a challenging goal.

Design/methodology/approach

This retrospective longitudinal observational study analyzed how this modality was used at the primary care level in Galicia, a region in the Northwest of Spain, in 2014 and 2015, focusing on demand, gender and age preferences, rural vs urban population and efficiency.

Findings

Of 28,472,852 consultations requested in this period, 9.0 percent were telephone consultations. Women requested more telephone consultations (9.9 percent of total consultations) than men (7.7 percent of total consultations). The highest demand occurred for the over 85 age group for both men and women. In both years, 2014 and 2015, the number of telephone consultations per inhabitant was higher in urban (0.53 and 0.69) than in rural areas (0.34 and 0.47). In 10.9 percent of cases, the telephone consultations required further face-to-face consultation.

Originality/value

Conventional voice telephone calls can efficiently replace conventional face-to-face consultations in primary healthcare in roughly 10 percent of cases. Women are more likely than men to use primary care services in both face-to-face and telephone consultation modalities. Public healthcare systems should consider implementing telephone consultations to deliver their services.
Does the business model canvas drive venture success?
Authors: Ladd Ted
Published: March 2018

Purpose

The purpose of this paper is to explore the efficacy of Osterwalder and Pigneur’s Business Model Canvas for 271 teams competing in a venture pitch competition during a cleantech accelerator program.

Design/methodology/approach

It uses competition results and data from a website used by participants to track their hypothesis construction and testing.

Findings

Teams that used the elements of customer segment, value proposition, key activities or key partnerships performed significantly better in the competition. Yet of all nine elements in the Canvas, only customer segmentation showed a significant linear bivariate correlation between the number of validated hypotheses and performance. Finally, teams that heavily used a triumvirate of elements composed of customer segmentation, value proposition and channel performed two times better than teams that barely used these elements.

Research limitations/implications

The findings of this exploratory analysis imply that the components of a business model that explain and predict early success might be different than those for a more mature firm.

Practical implications

These results suggest that practitioners could improve early performance by narrowing their scrutiny to just the triumvirate, because the Canvas may contain components that are unhelpful for entrepreneurs as they form a business model for their nascent venture.

Originality/value

This paper fills a gap by empirically testing the prediction that application of the Business Model Canvas drives venture success and providing a revise definition for a business model that is more appropriate for start-up ventures.
Towards new coopetition-based business models? The case of Netflix on the French market
Authors: Daidj Nabyla , Egert Charles
Published: March 2018

Purpose

The purpose of this research paper is to discuss the evolution in business models (BM) of one key player (Netflix) in the French online streaming video services market.

Design/methodology/approach

The paper is based on a qualitative approach (Netflix case study based on secondary data) to reduce the gap between theory and business practice.

Findings

Through technological convergence, the movie and video industry has seen dramatic changes in the means of consumption, forcing the traditional media players to evolve and adapt their strategy and BM to face new entrants (mainly IT companies). Coopetitive practices have been developed in spite of a fierce competition in the French market with impact on BM. Netflix is representative of this evolution.

Research limitations/implications

This qualitative research is based on a case study. The results of a single case study cannot be used to make generalizations. Certainly, this paper represents only a first step. Further research is required in this field.

Originality/value

The originality of this paper is to expand the understanding of BMs by including various strategic and marketing perspectives and analyze the impact of coopetitive practices on the BM of one key player: Netflix.
Holistic performance management of virtual teams in third-party logistics environments
Authors: Eaidgah Youness , Abdekhodaee Amir , Najmi Manoochehr , Arab Maki Alireza
Published: March 2018

Purpose

The purpose of this paper is to investigate the use of an integrated approach for performance improvement of virtual teams (VTs) in third-party logistics (3PL) through the integration of performance management (PM), visual management (VM) and continuous improvement (CI) initiatives into one coherent system. The paper will also propose a methodological framework to establish such a system. The intended integrated system is called as integrated visual management (IVM) throughout this paper.

Design/methodology/approach

This research is based on a case study that took place in a 3PL context with 19 VTs of different sizes spread across Australia. Many major 3PL companies provide their services either internationally or nationwide and therefore use VTs on a regular basis. The selected company does the same. This case was picked as representative of the many complexities which VTs face in 3PL settings, e.g. geographical and temporal separations; different skill levels within the team and between different team bases; multi-teaming system; high staff turnover; recurring performance problems and firefighting approach to problem-solving; and highly demanding performance requirements from clients. Further, this case study, being of a newly established contract and team, enabled the observation of the team dynamic and complexities from the earliest stages. In addition, as the main author of the paper was part of the managerial layer of the studied VT, this provided it a unique opportunity to escape the usual bureaucracy and rather focus on the research. This study also includes a literature review on VTs along with PM, VM and CI, which comprises IVM.

Findings

It was found that an integrated approach to PM, VM and CI was effective in systematically improving the VT performance. The framework for implementing IVM was productive and enabled to successfully plan and deploy the improvement intentions. Even though the team was highly virtual and encompassed a range of situational challenges, including different skill levels, a multi-teaming system and a high staff turnover, nevertheless, through IVM, the results met and exceeded performance targets on a sustainable base. Inventory record accuracy, dispatch on time, delivery in full on time and dock to stock were improved by 45, 62, 22 and 25 per cent on average, respectively.

Originality/value

The originality of the paper comes from its methodological approach to performance improvement for VTs in 3PL contexts through integrating PM, VM and CI systems into one coherent system, IVM.
Validation of a QuEChERS‐Based Gas Chromatography‐Mass Spectrometry (GC‐MS) Method for Analysis of Phthalate Esters in Grain Sorghum
Authors: Sun Xiaotao , Dong Wei , Liu Miao , Shen Caihong , Zhang Yuyu , Sun Jinyuan , Sun Baoguo , Li Hehe , Chen Feng
Published: March 2018

A modified QuEChERS method coupled with gas chromatography‐mass spectrometry (GC‐MS) was developed for analysis of 14 phthalate esters (PAEs) in grain sorghum (GS). Chemical extraction was done with acetonitrile followed by dispersive‐solid phase extraction technique with a mixture of sorbents including primary secondary amine and octadecyl silica. Under the optimized condition, the matrix‐matched calibration curves for all PAEs showed good linear relationship in the concentration range between 5 and 500 μg/L with correlation coefficients (R2) better than 0.99. Mean recoveries were between 82.0% and 120.2% at spiking levels of 0.06, 0.6, and 2.0 mg/kg with RSD of 0.3% to 7.8% (n = 5) for intra‐day precision and 1.2% to 7.6% (n = 5) for inter‐day precision. The LODGS and LOQGS for 14 PAEs were between 0.4 and 10.0 μg/kg and 0.5 and 20.0 μg/kg, respectively. Analysis of 32 commercial GS samples revealed that dimethyl‐, diethyl‐, diisobutyl‐, dibutyl‐, and di‐ (2‐ethylhexyl) phthalate esters were detected in all of the analytes. In addition, content‐color scale model was applied to visualize the concentration differences of PAEs in real GS samples. Principal component analysis of PAEs revealed that the GS samples did not have a distinctive cluster based on their geographic origins. The established method was proven to be simple, accurate, and effective for analysis of PAEs in GS, which might also be applied for analysis of PAEs in other matrices.

Practical Application

A modified QuEChERS‐based GC‐MS method was developed for the determination of phthalate esters (PAEs) in grain sorghum (GS). The ubiquitous presence of PAEs can migrate into GS. Therefore, evaluation of the total content of PAEs in GS is helpful to understand its impact of overall pollution level on other foods. This study has provided some basic information in terms of the content and contamination of PAEs in GS, which is helpful to establish relevant standards and risk assessment of GS for the government.
Yeast culture dietary supplementation modulates gut microbiota, growth and biochemical parameters of grass carp
Authors: Liu Han , Li Juntao , Guo Xianwu , Liang Yunxiang , Wang Weimin
Published: March 2018

Gut microbiota contributes positively to the physiology of their host. Some feed additives have been suggested to improve livestock health and stimulate growth performance by modulating gut bacteria species. Here, we fed grass carp with 0 (control), 8% (Treat1), 10% (Treat2), 12% (Treat3) and 16% (Treat4) of yeast culture (YC) for 10 weeks. The gut microbiota was analysed by 16S rRNA gene V3‐4 region via an Illumina MiSeq platform. PCoA test showed that gut bacterial communities in the control and Treat3 formed distinctly separate clusters. Although all the groups shared a large size of OTUs as a core microbiota community, a strong distinction existed at genus level. Treat3 contained the highest proportion of the beneficial bacteria and obviously enhanced the capacity of amino acid, lipid metabolism and digestive system. In addition, Treat3 significantly improved the fish growth and increased the liver and serum T‐SOD activities while dramatically decreased the liver GPT and GOT. Collectively, these findings demonstrate the beneficial effects of YC feeding on gut microbiota, growth and biochemical parameters and Treat3 might be the optimal supplementation amount for grass carp, which opens up the possibility that a new feed additive can be developed for healthy aquaculture.
Impact of salvage treatment modalities in patients with positive FDG‐PET/CT after R‐CHOP chemotherapy for aggressive B‐cell non‐Hodgkin lymphoma
Authors: Chin Vicky , Fulham Michael , Hertzberg Mark , Jackson Michael , Lindeman Robert , Brighton Timothy , Kidson‐Gerber Giselle , Wegner Eva A , Cheung Carol , MacCallum Susan , Williams Janet , Thompson Stephen R
Published: March 2018

Introduction

To compare outcomes of different salvage treatment modalities in patients with aggressive B‐cell non‐Hodgkin lymphoma (NHL) who remain FDG‐PET positive after R‐CHOP chemotherapy. Existing data on these patients with FDG‐PET primary refractory disease are limited.

Methods

Patients with diffuse large B‐cell lymphoma or grade 3 follicular lymphoma were retrospectively reviewed from the Prince of Wales Hospital databases. Eligibility criteria were: age≥18 years, treated with R‐CHOP, with positive post‐chemotherapy FDG‐PET. Salvage treatment modalities were: radical radiotherapy (RT, dose≥30 Gy), high dose chemotherapy and autologous stem cell transplant (ASCT), or non‐radical management. Survival was calculated from date of post‐chemotherapy FDG‐PET to last follow‐up.

Results

Twenty‐six patients from 2003–2015 met the inclusion criteria. Median age was 60 (range 19–84). Most had adverse baseline features: 21 (81%) stage III‐IV, 24 (92%) bulky disease and nine (35%) skeletal involvement. Characteristics of PET‐positivity post‐chemotherapy were single site in 16 (62%), sites of prior bulk in 24 of 24, skeletal sites in five of nine, and able to be encompassed by RT in 21 (81%). Salvage treatment was: radical RT in 17 (65%), ASCT in four (15%) and non‐radical in five (20%). Median follow‐up of surviving patients was 31 months. Kaplan–Meier estimates of 3‐year PFS and OS were 41% and 52%, respectively. By salvage modality, 3‐year PFS was 51% for RT, 25% for ASCT and 20% for non‐radical treatment, (P = 0.453); 3‐year OS was respectively 65%, 25% and 40% (P = 0.173).

Conclusion

Patients with FDG‐PET positive disease after R‐CHOP for aggressive B‐cell NHL are salvageable with radiotherapy.
Diagnostic accuracy of diffusion‐weighted imaging‐ magnetic resonance imaging compared to positron emission tomography/computed tomography in evaluating and assessing pathological response to treatment in adult patients with lymphoma: A systematic review
Authors: Fitzpatrick John J , Ryan Miriam A , Bruzzi John F
Published: March 2018

The use of Positron emission tomography/computerised tomography (PET/CT) is well established in the staging and assessment of treatment response of lymphoma. Recent studies have suggested that whole body diffusion‐weighted imaging –magnetic resonance imaging (WB‐DW‐MRI) may be an alternative to PET/CT in both staging and assessment of treatment response. A systematic review was performed to assess the ability of DW‐MRI in the assessment of treatment response in lymphoma. Pubmed, Medline, Web of Science and Embase databases were queried for studies examining whole body DW‐MRI compared to PET/CT in adult patients using a protocol of search terms. We carried out an extensive assessment of titles, abstracts and full texts of relevant paper as well as quality assessment with the Quality Assessment of Diagnostic Accuracy (QUADAS‐2) tool. Eight studies were found to meet the criteria and were included in our review and analysis. Overall, the quality of studies was found to be moderate, with good inter‐rater agreement (K = 0.74). Data analysis showed that lesion‐based assessment in 5 studies with pooled results had a sensitivity and specificity of 94.7% and 99.3%. Assessment with Cohen's Kappa coefficient showed agreement to be excellent (K = 0.88). Three studies were included for qualitative analysis, two of which showed good equivalence between PET/CT and DW‐MRI. WB‐DWI‐MRI can be considered a sensitive and specific method for assessing treatment response in Lymphoma without the use of ionising radiation or administration of F‐18 Flurodeoxyglucose. Further studies are needed to evaluate the optimum b‐values in assessing treatment response.
Group‐specific environmental sequencing reveals high levels of ecological heterogeneity across the microsporidian radiation
Authors: Williams Bryony A. P. , Hamilton Kristina M. , Jones Meredith D. , Bass David
Published: March 2018

The description of diversity is a key imperative in current biological studies and has been revolutionised by the molecular era that allows easy access to microbial diversity not visible to the naked eye. Broadly targeted SSU rRNA gene amplicon studies of diverse environmental habitats continue to reveal new microbial eukaryotic diversity. However, some eukaryotic lineages, particularly parasites, have divergent SSU sequences, and are therefore undersampled or excluded by the methodologies used for SSU studies. One such group is the Microsporidia, which have particularly divergent SSU sequences and are rarely detected in even large‐scale amplicon studies. This is a serious omission as microsporidia are diverse and important parasites of humans and other animals of socio‐economic importance. Whilst estimates of other microbial diversity are expanding, our knowledge of true microsporidian diversity has remained largely static. In this work, we have combined high throughput sequencing, broad environmental sampling and microsporidian‐specific primers to broaden our understanding of the evolutionary diversity of the Microsporidia. Mapping our new sequences onto a tree of known microsporidian diversity we uncover new diversity across all areas of the microsporidian tree and uncover clades dominated by novel sequences, with no close described relatives.
The effect of Psephodiplosis rubi (Diptera: Cecidomyiidae) leaf galls on the secondary metabolite profiles of two congeneric host plants
Authors: Hall Casey R , Robertson Luke P , Carroll Anthony R , Kitching Roger L
Published: March 2018

Galling insects have the unique ability to control the secondary chemistry of their host plants. Galled plant tissue often has higher concentrations of these secondary compounds compared with surrounding plant material. In this study, we used nuclear magnetic resonance (NMR) spectroscopy metabolomics techniques to investigate the effect of galls induced by Psephodiplosis rubi Kolesik, on the profiles of secondary metabolites in its two Rubus host plants in subtropical rainforest. We isolated four triterpenoid compounds from both Rubus species. Concentrations of individual triterpenes were not significantly different in galled and non‐galled leaves; however, the concentration of 2‐oxopolomic acid was significantly negatively correlated with gall abundance. At the interspecific level, non‐galled leaves from both Rubus species were chemically indistinguishable in principal component analysis analyses, while galled leaves showed slight chemical differences. Surprisingly, there was very little difference in metabolic profiles of galled and non‐galled leaves at the intraspecific level. Using NMR, we were able to detect slightly different chemical responses in two congeneric host plant species induced by P. rubi galls. We demonstrate how NMR can be used to detect interspecific chemical differences of plants in ecological studies.
Maternal‐fetal cross talk through cell‐free fetal DNA, telomere shortening, microchimerism, and inflammation
Authors: Cheng Shi‐Bin , Davis Sarah , Sharma Surendra
Published: March 2018

There exists a strong correlation between unscheduled inflammation at the maternal‐fetal interface and the continuum of pregnancy complications. In normal pregnancy, immunological tolerance is established to protect the semi‐allogeneic fetus. There has been extensive research on how the immunity, endovascular trophoblast migration, and hormonal nexus are orchestrated during pregnancy at the maternal‐fetal interface to program a normal pregnancy outcome. It is not clear what contributes to the plasticity of uterine immune tolerance, fetal survial, and long‐term post‐partum health of the mother and the offspring. Old and new concepts have reemerged and emerged that include cell‐free fetal DNA (cffDNA), telomere shortening, microchimerism involving bidirectional migration of maternal and fetal cells, and pregnancy as a stress factor. The question is how these pathways converge in a gestational age‐dependent manner to contribute to the health of the mother and the offspring later in life and respond to an array of inflammatory challenges. In this Review, we provide pertinent discussion on maternal‐fetal cross talk through cffDNA, telomere shortening, and microchimerism in the context of inflammatory and anti‐inflammatory settings, particularly how these pathways lead to normal and adverse pregnancy outcomes.
Should I Stay or Should I Go? Leaders, Exile, and the Dilemmas of International Justice
Authors: Krcmaric Daniel
Published: March 2018

In recent years, several oppressive leaders have been arrested and extradited to international courts. What are the consequences of this global justice cascade? I address this question by examining patterns of exile. I show that the justice cascade has a differential effect on leaders based on their culpability (whether they presided over atrocity crimes). In the past, culpable and nonculpable leaders went into exile at virtually identical rates. Today, however, culpable leaders are about six times less likely to flee abroad because exile no longer guarantees a safe retirement. These findings raise stark implications for existing research that debates whether international justice deters atrocities or prolongs conflicts. My results about exiled leaders, I explain, imply that the justice cascade should deter atrocities and prolong conflicts. Thus, instead of debating whether international justice is helpful or harmful, future scholarship should carefully consider the trade‐offs it creates.
Preliminary study of the homologous recombination repair pathway in mouse spermatogonial stem cells
Authors: Le W. , Qi L. , Xu C. , Xiang Z. , Mao Z. , Zhang J. , Xu J. , Wu D.
Published: March 2018

The present study was designed to detect DNA repair response through the homologous recombination pathway in mouse spermatogonial stem cells. Mouse spermatogonial stem cells (mSSCs) were obtained from the adult DBA/2 mouse testes by MACS sorting. mSSCs and mice animals were divided into four groups (30 min, 2, 24 h, control) and treated with ionizing irradiation while the control group received pseudo‐irradiation. Proteins involved in the homologous recombination pathway (γH2AX, ATM, RAD51, CtIP, and RPA2) were assessed in mSSCs both in vitro and in vivo. Moreover, the non‐homologous end‐joining or homologous recombination (NHEJ/HR) reporter plasmids were transfected into mSSCs to assess NHEJ/HR pathway activity after DNA double‐strand break (DSB). γH2AX, a classical DNA DSB marker, was absent in mSSCs both in vivo and in vitro after DSB repair, but was highly expressed in other tissue stem cells. In addition, ATM and phosphorylated ATM (p‐ATM) were involved in DNA damage response (DDR) in mSSCs. p‐ATM foci were overexpressed immediately after irradiation (30 min and 2 h), but gradually decreased over the repair time. The HR pathway‐related proteins, CtIP and RPA2 were negatively regulated after treatment in Western blot (WB). NHEJ/HR reporter plasmid transfection indicated that the HR pathway played a minor role in mSSCs during DDR, consistent with the WB findings. This study demonstrates that mSSCs may have a unique response to DNA damage since crucial proteins involved in HR pathway were negatively regulated after DSB. In addition, the expression level of p‐ATM, but not γH2AX, was increased after DSB, suggesting that DNA damage repair in mSSCs might be a γH2AX‐independent response. Furthermore, the HR pathway may play a minor role during DDR in mSSCs.
Efficacy and safety of intravitreal anti‐tumour necrosis factor drugs in adults with non‐infectious uveitis – a systematic review
Authors: Leal Inês , Rodrigues Filipe B , Sousa David Cordeiro , Romão Vasco C , Duarte Gonçalo S , Carreño Ester , Dick Andrew D , Marques‐Neves Carlos , Costa João , Fonseca João Eurico
Published: March 2018

Anti‐tumour necrosis factor (TNF) drugs have been extensively used in non‐infectious uveitis (NIU), when corticosteroids or conventional immunosuppressive drugs cannot adequately control inflammation or intolerable side‐effects occur. However, systemic anti‐TNF therapies are also associated with a myriad of side‐effects. Therefore, intravitreal administration of anti‐TNF biologics has been employed to minimize patient morbidity and systemic adverse effects, while maintaining therapeutic effectivity. We undertook a systematic review to determine evidence of efficacy and safety of intravitreal administration of anti‐TNF drugs in adults with NIU. We conducted this systematic review according to the PRISMA guidelines. The protocol was registered with PROSPERO (CRD42016041946). We searched CENTRAL, MEDLINE and EMBASE, from inception to April 2017, as well as clinical trial registries and grey literature. The qualitative analysis included all studies of adult patients with a diagnosis of NIU and who received intravitreal anti‐TNF drugs with a 4‐week minimum follow‐up. A total of 4840 references were considered for title and abstract screening. Seven full texts were screened, and five studies were considered for analysis. All studies were open‐label, single‐centre, prospective, non‐randomized, interventional case series with a follow‐up between 4 and 26 weeks, employing either adalimumab in two studies and infliximab in three. Three studies showed a treatment effect of anti‐TNF intravitreal injections, while one study revealed short‐term improvement and one study revealed no efficacy of anti‐TNF intravitreal therapy. None of the studies reported ocular adverse effects but only two studies included electrophysiological assessment in the safety analysis and no study assessed systemic human anti‐drug antibodies. The available evidence is not sufficiently robust to conclude about the clinical effectivity of intravitreal anti‐TNF in NIU and so no recommendation can be made. In conclusion, intravitreal injection of anti‐TNF antibodies remains a possible treatment option to be explored through robust clinical investigation.
Safety and feasibility of laparoscopic gastrectomy accompanied by D1+ lymph node dissection for early gastric cancer in elderly patients
Authors: Yasukawa Daiki , Kadokawa Yoshio , Kato Shigeru , Aisu Yuki , Hori Tomohide
Published: March 2018

Introduction

The age of patients with gastric cancer has increased worldwide. The aim of this study was to investigate the safety and feasibility of laparoscopic gastrectomy (LG) for early gastric cancer in elderly patients.

Methods

We retrospectively investigated 221 consecutive patients who underwent LG for early gastric cancer during a 5‐year period (January 2010 to December 2014). We divided the patients into two groups: elderly patients (≥75 years old) and younger patients (<75 years old). We compared these two groups with respect to clinical characteristics, histopathological findings, intraoperative factors, and postoperative outcomes.

Results

The preoperative characteristics were similar in both groups. Except for the number of harvested lymph nodes (42.0 vs 34.9; P = 0.0016), the short‐term operative outcomes, including postoperative complications and histopathological findings, were comparable between the two groups. Although significantly fewer lymph nodes were harvested in the elderly group, the overall survival and relapse‐free survival rates did not significantly differ between the groups. Postoperative complications, such as acute cholecystitis and internal hernia, occurred during the long‐term postoperative period after LG, and these unexpected complications were more frequently observed in elderly patients. All elderly patients required additional emergent surgeries for delayed complications.

Conclusion

The outcomes of LG for early gastric cancer in elderly patients seem to be reasonable. Aggressive lymph node dissection may be omissible in elderly patients with acceptable results. LG can be a safe and feasible procedure in elderly patients. However, the higher rate of delayed but urgent complications during the long‐term postoperative period must be considered.
Carbon Monoxide‐Releasing Molecule Enhances Coagulation and Decreases Fibrinolysis in Normal Canine Plasma
Authors: Donaghy Dillon , Yoo Seung , Johnson Tyler , Nielsen Vance , Olver Christine
Published: March 2018

The dog is an important companion animal and also purpose‐bred for research studies. Coagulopathies in dogs are common, although the availability of blood products for therapy is inconsistent throughout the profession. A pro‐coagulant therapeutic that is readily available and easily stored would be useful for the treatment of coagulopathies. Tricarbonyldichlororuthenium (II) dimer [Carbon monoxide‐releasing molecule‐2 (CORM‐2)] acts as a prothrombotic agent in plasma by increasing the velocity of clot formation and clot strength, and by decreasing the clot's vulnerability to fibrinolysis. We sought to test CORM‐2's effect on coagulation and fibrinolysis in vitro in canine plasma using thromboelastography. Measures of the rate of clot formation and clot strength in plasma without CORM‐2 were highly correlated with fibrinogen concentration. We found that CORM‐2 significantly enhanced the rate of clot formation and clot strength and significantly reduced the rate of fibrinolysis and the clot lysis time. The per cent change in rate of clot formation and clot strength was not significantly correlated with fibrinogen concentration, indicating that CORM‐2's pro‐coagulant effect is not dependent on fibrinogen concentration. This study corroborates studies in other species that show that CORM‐2 is pro‐coagulant in plasma, and lays the groundwork for developing CORM‐2 as a therapeutic agent for canine coagulopathies. Future studies will evaluate the effect of CORM‐2 on whole blood both in vitro and in vivo.
Bayesian Nonparametric Generative Models for Causal Inference with Missing at Random Covariates
Authors: Roy Jason , Lum Kirsten J. , Zeldow Bret , Dworkin Jordan D. , Re Vincent Lo , Daniels Michael J.
Published: March 2018

We propose a general Bayesian nonparametric (BNP) approach to causal inference in the point treatment setting. The joint distribution of the observed data (outcome, treatment, and confounders) is modeled using an enriched Dirichlet process. The combination of the observed data model and causal assumptions allows us to identify any type of causal effect—differences, ratios, or quantile effects, either marginally or for subpopulations of interest. The proposed BNP model is well-suited for causal inference problems, as it does not require parametric assumptions about the distribution of confounders and naturally leads to a computationally efficient Gibbs sampling algorithm. By flexibly modeling the joint distribution, we are also able to impute (via data augmentation) values for missing covariates within the algorithm under an assumption of ignorable missingness, obviating the need to create separate imputed data sets. This approach for imputing the missing covariates has the additional advantage of guaranteeing congeniality between the imputation model and the analysis model, and because we use a BNP approach, parametric models are avoided for imputation. The performance of the method is assessed using simulation studies. The method is applied to data from a cohort study of human immunodeficiency virus/hepatitis C virus co-infected patients.
Identification of potent and selective small molecule inhibitors of the cation channel TRPM4
Authors: Ozhathil Lijo Cherian , Delalande Clémence , Bianchi Beatrice , Nemeth Gabor , Kappel Sven , Thomet Urs , Ross‐Kaschitza Daniela , Simonin Céline , Rubin Matthias , Gertsch Jürg , Lochner Martin , Peinelt Christine , Reymond Jean‐Louis , Abriel Hugues
Published: March 2018

Background and Purpose

TRPM4 is a calcium‐activated non‐selective cation channel expressed in many tissues and implicated in several diseases, and has not yet been validated as a therapeutic target due to the lack of potent and selective inhibitors. We sought to discover a novel series of small‐molecule inhibitors by combining in silico methods and cell‐based screening assay, with sub‐micromolar potency and improved selectivity from previously reported TRPM4 inhibitors.

Experimental Approach

Here, we developed a high throughput screening compatible assay to record TRPM4‐mediated Na+ influx in cells using a Na+‐sensitive dye and used this assay to screen a small set of compounds selected by ligand‐based virtual screening using previously known weakly active and non‐selective TRPM4 inhibitors as seed molecules. Conventional electrophysiological methods were used to validate the potency and selectivity of the hit compounds in HEK293 cells overexpressing TRPM4 and in endogenously expressing prostate cancer cell line LNCaP. Chemical chaperone property of compound 5 was studied using Western blots and electrophysiology experiments.

Key Results

A series of halogenated anthranilic amides were identified with TRPM4 inhibitory properties with sub‐micromolar potency and adequate selectivity. We also showed for the first time that a naturally occurring variant of TRPM4, which displays loss‐of‐expression and function, is rescued by the most promising compound 5 identified in this study.

Conclusions and Implications

The discovery of compound 5, a potent and selective inhibitor of TRPM4 with an additional chemical chaperone feature, revealed new opportunities for studying the role of TRPM4 in human diseases and developing clinical drug candidates.
Co‐expression of μ and δ opioid receptors by mouse colonic nociceptors
Authors: Guerrero‐Alba Raquel , Valdez‐Morales Eduardo Emmanuel , Jiménez‐Vargas Nestor Nivardo , Bron Romke , Poole Daniel , Reed David , Castro Joel , Campaniello Melissa , Hughes Patrick A , Brierley Stuart M , Bunnett Nigel , Lomax Alan E , Vanner Stephen
Published: March 2018

Background and Purpose

To better understand opioid signalling in visceral nociceptors, we examined the expression and selective activation of μ and δ opioid receptors by dorsal root ganglia (DRG) neurons innervating the mouse colon.

Experimental Approach

DRG neurons projecting to the colon were identified by retrograde tracing. δ receptor‐GFP reporter mice, in situ hybridization, single‐cell RT‐PCR and μ receptor‐specific antibodies were used to characterize expression of μ and δ receptors. Voltage‐gated Ca2+ currents and neuronal excitability were recorded in small diameter nociceptive neurons (capacitance <30 pF) by patch clamp and ex vivo single‐unit afferent recordings were obtained from the colon.

Key Results

In situ hybridization of oprm1 expression in Fast Blue‐labelled DRG neurons was observed in 61% of neurons. μ and δ receptors were expressed by 36–46% of colon DRG neurons, and co‐expressed by ~25% of neurons. μ and δ receptor agonists inhibited Ca2+ currents in DRG, effects blocked by opioid antagonists. One or both agonists inhibited action potential firing by colonic afferent endings. Incubation of neurons with supernatants from inflamed colon segments inhibited Ca2+ currents and neuronal excitability. Antagonists of μ, but not δ receptors, inhibited the effects of these supernatant on Ca2+ currents, whereas both antagonists inhibited their actions on neuronal excitability.

Conclusions and Implications

A significant number of small diameter colonic nociceptors co‐express μ and δ receptors and are inhibited by agonists and endogenous opioids in inflamed tissues. Thus, opioids that act at μ or δ receptors, or their heterodimers may be effective in treating visceral pain.
Upregulation of CXCR4 through promoter demethylation contributes to inflammatory hyperalgesia in rats
Authors: Li Feng , Xue Zhou‐Ya , Yuan Yuan , Huang Sai‐Sai , Fan Yi‐Hui , Zhu Xiang , Wei Lei
Published: March 2018

Aim and methods

Chronic pain associated with inflammation is a common clinical problem, and the underlying mechanisms yet are incompletely defined. DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under inflammatory pain condition remain largely unknown. Here, we investigated how chemokine receptor CXCR4 expression is regulated by DNA methylation and how it contributes to inflammatory pain induced by complete Freund's adjuvant (CFA) in rats.

Results

Intraplantar injection of CFA could not only induce significant hyperalgesia in rats, but also significantly increase the expression of CXCR4 mRNA and protein in the dorsal root ganglion (DRG). Intrathecal injection of CXCR4 antagonist AMD3100 significantly relieved hyperalgesia in inflammatory rats in a time‐ and dose‐dependent manner. Bisulfite sequencing and methylation‐specific PCR demonstrate that CFA injection led to a significant demethylation of CpG island at CXCR4 gene promoter. Consistently, the expression of DNMT3b was significantly downregulated after CFA injection. Online software prediction reveals three binding sites of p65 in the CpG island of CXCR4 gene promoter, which has confirmed by the chromatin immunoprecipitation assay, CFA treatment significantly increases the recruitment of p65 to CXCR4 gene promoter. Inhibition of NF‐kB signaling using p65 inhibitor pyrrolidine dithiocarbamate significantly prevented the increases of the CXCR4 expression.

Conclusion

Upregulation of CXCR4 expression due to promoter demethylation followed by increased recruitment of p65 to promoter of CXCR4 gene contributes to inflammatory hyperalgesia. These findings provide a theoretical basis for the treatment of chronic pain from an epigenetic perspective.
Patient‘s perspective on long‐term complications after superficial parotidectomy for benign lesions: Prospective analysis of a 2‐year follow‐up
Authors: Wolber P. , Volk G.F. , Horstmann L. , Finkensieper M. , Shabli S. , Wittekindt C. , Klussmann J.P. , Guntinas‐Lichius O. , Beutner D. , Grosheva M.
Published: March 2018

Objective

Evaluation of patients′ perspective on long‐term complications after superficial parotidectomy for benign lesions.

Design

A prospective nonrandomized controlled multicenter study.

Setting

Three university‐based tertiary referral centers (Departments of Otorhinolaryngology of Cologne, Jena and Giessen; all in Germany).

Participants

130 adult patients, who underwent a primary superficial parotidectomy for benign tumors of the parotid gland, were consecutively included from 09/2010 to 05/2012. 61 patients completed every follow‐up examination.

Main outcome measures

Complications were evaluated using the validated German‐language questionnaire Parotidectomy Outcome Inventory 8 at six, 12 and 24 months after surgery. Pain intensity was assessed on a numeric rating scale (NRS) at each follow‐up visit.

Results

At 6 months after surgery, 90% characterized hypoesthesia as the most disturbing problem, followed by fear of revision surgery (57%) and scar (56%). Facial palsy (14%) posed the minor problem. Hypoesthesia improved significantly during the follow‐up period (all P < .05), but still posed a problem for 78% of the patients after 2 years. Pain, which initially bothered 53% of the patients, significantly decreased, whereas impairment due to Frey′s syndrome significantly increased during the follow‐up (6 vs 24 months; P = .002 and P = .001, respectively). Scar, substance loss, xerostomia, facial palsy, and anxiety affected patients with unvarying severity during the 2 years (all P > .05).

Conclusions

From patients′ perspective, sensation loss posed the major subjective problem after superficial parotidectomy. Appearance of the scar, and fear of revision surgery impaired more than 50% of the patients in their daily life without significant improvement during the 2 years postoperatively. Although superficial parotidectomy is a highly standardized and safe procedure, limited parotidectomy for proven benign parotid salivary gland neoplasms is more likely to result in patients with minimal or no displeasing complications.