bluuebunny/crossref_metadata_2025 huggingface dataset:
Service creativity reinforcement and firm performance
Authors: Tsai Kuen-Hung , Huang Stephen Chi-Tsun
Published: January 2020

Purpose

Many service firms have adopted creativity reinforcement mechanisms to manage employee-based service creativity so as to pursue their performance growth. However, its impact on firm performance has rarely been investigated in the extant research. The purpose of this paper is to satisfy this knowledge gap through an examination of how service creativity reinforcement (SCR) affects a firm’s performance.

Design/methodology/approach

Two samples were used to test the hypotheses. The first sample included a total of 4,381 service firms and was analyzed by using a traditional moderated regression method in relation to sales growth as the outcome variable. Due to a number of missing values, the second sample was reduced to 1,481 service firms. This sample was analyzed by using a moderated fractional regression method and the outcome variable was innovation performance. Furthermore, a multi-valued treatment approach with the augmented inverse-propensity weighted estimator was adopted to assess the performance effect that was associated with each of the SCR mechanisms.

Findings

Statistical analyses suggested that SCR positively affected both the firm’s performance and its innovation performance. Specifically, the stronger performance effects of SCR were associated with firms that had high innovation intensity, were small service firms and were part of the knowledge-intensive business service (KIBS) sector. The results also found that brainstorming sessions, a multi-disciplinary team approach, task rotation and non-financial incentives had greater performance effects than other mechanisms, especially for firms in the KIBS sector that had high innovation intensity. In addition, the results indicated that team-level mechanisms were more effective in developing highly innovative services than were individual-level mechanisms.

Originality/value

This study has contributed to the service literature by developing a contingency framework for SCR. This study has also advanced service research through the presentation of contextual effects associated with each mechanism of SCR.
The mediating role of relative communicative behavior on the relationship between ethical leadership and organizational identification
Authors: Abu Bakar Hassan , Omillion-Hodges Leah
Published: January 2020

Purpose

The purpose of this paper is to examine the underlying process of a relative leader–member dyadic communication behavior linking association between ethical leadership and organizational identification in Malaysia’s diverse workplace.

Design/methodology/approach

Based on relational dyadic communication, social comparison and social identity theories, the authors develop a mediation model. The model illustrates the link between the relative leader–member dyadic communication behavior processes, ethical leadership and organizational identification. The model was tested on a sample of 273 group members from 58 groups working in large government link corporations in Malaysia.

Findings

Results of hierarchical regression analysis provide support for the model. The authors found that ethical leadership was positively related to relative leader–member dyadic communication behavior based on the norms and values ofbudicontext.Budiis a social norm in the Malaysian context that helps employees to know how they should interact with others.Budiis manifested through the use of language and should be used or present in the interactions or conversations with others.

Originality/value

The relative shared norms and values ofbudimediate the relationship between ethical leadership and organizational identification after controlling for the perception of individual leader–member dyadic communication behavior on norms and values ofbudi.
Markov-switching impacts of housing-market expectations on credit markets
Authors: Huang MeiChi
Published: January 2020

Purpose

The purpose of this paper is to investigate linkages between households’ expectations and credit markets in the housing crisis.

Design/methodology/approach

In the Markov-switching framework, the sample period is classified into high- and low-impact regimes based on impacts of expectations on default rates, and the good-time-to-buy (GTTB) index is chosen to proxy for expectations toward the housing-market dynamics.

Findings

The results suggest that in high-impact regimes, optimistic expectations are substantially associated with lower defaults for all default rates analyzed, and second mortgage defaults are more sensitive to households’ expectations than first mortgage defaults. In low-impact regimes, the GTTB index significantly influences composite and first-mortgage default rates, but its impact is insignificant for second mortgage and bankcard default rates.

Originality/value

The results provide compelling evidence that households’ expectations play more important roles in credit markets in turmoil periods.
Adequacy of energy and protein intake among hospitalized patients on therapeutic diet in government hospitals
Authors: Kong Jian Pei , Baharom Basmawati , Jamhuri Norshariza , Jamli Khalizah , Mohd Yazid Siti Farah Zaidah , Ashiquin Norafidza , Isnin Lina , Leow Chooi Wah , Lim Siew Mee
Published: January 2020

Purpose

The provision of meals has long been regarded as an essential part of treatment of hospitalized patients complementing medical procedures and nursing management. Today, despite changes in the health-care landscape, which focused on improving the quality and efficiency of hospital care, malnutrition among inpatient was still a common worldwide concern.

Design/methodology/approach

This was a multi-centre, randomized study conducted in 21 study sites comprising 21 state and specialist government hospitals under the Ministry of Health, Malaysia. The sample size for this study was calculated with purposive sampling method, followed by proportionate sampling to determine the random sample size of each of the study sites. The total sample size required for this study was 2,759 subjects. A validated data collection form was used in the study.

Findings

Only 32.2 % and 37.6 % of subjects achieved adequate energy and protein intake, respectively, during their admission to medical ward. The study result showed that the overall mean energy and protein intake was 794.6 ± 487.8 kcal and 35.2 ± 24.3 g, respectively. The estimated energy (p = 0.001) and protein (p = 0.001) intake of all study sites was significantly lower compared to the adequacy value.

Research limitations/implications

The adequacy intake in this study was only carried out in medical wards, thus reproducible result among other wards in different study sites could not be confirmed. Besides, this study assumed that the portion eaten by subjects during lunch and dinner was the same, and therefore, either one was recorded together with breakfast and either lunch or dinner to represent a subject’s daily intake.

Originality/value

This was the first nationwide study to report the adequacy of energy and protein intake of patients receiving therapeutic diets in the government hospital setting in Malaysia.
Teasing out fieldwork challenges with e-mail methods in cross-border research
Authors: Ingley Coral , Singh Smita , Malkani Alanah
Published: January 2020

Purpose

The purpose of this paper is twofold: first, to reflect on the value of e-mails for recruiting and interviewing in a specific context in qualitative research, and second, to reflect on the benefits of the reflexive practice in sharing the research experience for gaining a deeper understanding of the field. The purpose is to raise points for consideration in research design for the e-mail method in this type of study.

Design/methodology/approach

The paper draws on reflexivity and integrates fieldwork experiences to present the shared reflections and insights into the enabling and constraining aspects of using e-mail interviews with hard-to-access participants such as senior executives of international businesses.

Findings

Closer consideration needs to be given to the use of e-mail interviewing in the research design for such studies, especially regarding culturally held preconceptions about the research environment and how the inevitable challenges in engaging in cross-border research may be resolved.

Originality/value

The paper yields unanticipated insights into the potential of e-mail interviewing for studies that require responses from key informants who are otherwise unlikely to participate in the research. The paper brings greater transparency to researchers regarding the realities of using the method in this context, and thus, it expands the hitherto small repertoire of such studies in qualitative international business research. The contribution also lies in the value of deliberately creating a space for reflexive conversations that open the possibility of more profound understandings in qualitative research.
The quest for genuine business agility
Authors: Denning Stephen
Published: January 2020

Purpose

The article warns that genuine business agility is not easily achieved despite the many consultants offering their services as specialists. It lays out the elements of the best practice approach – the methodology of Agile management.

Design/methodology/approach

Using Toyota as an example, the article show how one company is taking an innovative approach to agile team work and decision making.

Findings

The concept of Agile management includes both operational agility – making the existing business more focused on customer value – and strategic agility – generating new products and services to bring in new customers.

Practical implications

The shadow of Agile management done too hastily or badly has fostered widespread cynicism.

Originality/value

The article is a clarion call to wake up bureaucratic organizations that pass decisions down a lengthy chain of command. The need now is to have decisions made as close as possible to those who have the best information to make the best decision, which often requires the teams themselves to be the deciders. 10;Leadership becomes a function shared by all the people participating in the team. The team itself becomes the leadership.
Tourism statistics, indicators and big data: a perspective article
Authors: Volo Serena
Published: January 2020

Purpose

This paper aims to discuss the evolution of tourism data and critically debates future perspective for producers and users of tourism data.

Design/methodology/approach

This paper provides a perspective on tourism data based on selected literature.

Findings

Industry developments, technological changes and novel methodologies have influenced tourism data sources. Closer attention to new data collection methods and novel analytics is required.

Research limitations/implications

A considerate and integrated system of tourism data (statistics, indicators, and big data) shall remain a priority for scholars and practitioners alike.

Practical implications

The thoughtful merging of tourists’ digital traces with industry data, the competences of data analysts and the theoretical strengths of tourism scholars will result in a redesign of the tourism data landscape.

Social implications

This perspective article provides a brief overview of the development and challenges related to the future use of tourism statistics, indicators and big data.

Originality/value

The paper offers a novel vision of tourism data by combining three different but complementary aspects of tourism data.
Guidelines for the treatment of skin and mucosal lesions in Behçet's disease: A secondary publication
Authors: Nakamura Koichiro , Iwata Yohei , Asai Jun , Kawakami Tamihiro , Tsunemi Yuichiro , Takeuchi Masaki , Mizuki Nobuhisa , Kaneko Fumio ,   Members of the Consensus Conference on Treatment of Skin and Mucosal Lesions (Committee of Guideline for the Diagnosis and Treatment of Mucocutaneous Lesions of Behçet's disease)
Published: January 2020

In the current study, we present guidelines for the diagnosis and treatment of the mucocutaneous lesions of Behçet's disease, which is a chronic inflammatory disease characterized by the involvement of various organs, including mucocutaneous, ocular, vascular, intestinal and central nervous system lesions. It is often identified in the Middle East Mediterranean to East Asia region. Skin manifestations include erythema nodosum, papulopustular lesions and thrombophlebitis, and mucosal manifestations include oral and genital ulcers. These mucocutaneous lesions are characteristically the first signs of Behçet's disease and are important to be recognized for the early diagnosis of the disease. Moreover, these manifestations also recur and persist over the long‐term course of the disease. The management of mucocutaneous lesions is important to prevent recurrence. We developed consensus guidelines that provide recommendations for general practitioners and dermatologists and physicians on the management of the mucocutaneous lesions of Behçet's disease.
Skin and hair abnormalities of Cantu syndrome: A congenital hypertrichosis due to a genetic alteration mimicking the pharmacological effect of minoxidil
Authors: Ohko Kentaro , Nakajima Kimiko , Nakajima Hideki , Hiraki Yoko , Kubota Kazuo , Fukao Toshiyuki , Miyatake Satoko , Matsumoto Naomichi , Sano Shigetoshi
Published: January 2020

Cantu syndrome is an autosomal dominant disorder, first described by Cantu in 1982, that is characterized by congenital hypertrichosis, characteristic facial anomalies and cardiomegaly. Recent investigations have revealed that this syndrome is caused by mutations of ABCC9, which encodes a regulatory subunit of SUR2, an adenosine triphosphate‐mediated potassium channel opener, expressed not only in smooth muscle but also in hair follicles. However, the abnormalities of skin and hair in patients with Cantu syndrome have not been well explored. We herein report three Japanese patients with Cantu syndrome and describe their specific skin manifestations and alterations in the histopathology of their hair follicles and sebaceous glands. Similar alterations were shared among those three patients and may be related to the function of SUR2, namely the regulation of hair follicle growth, because SUR2 is a known pharmacological target of minoxidil.
Intracellular proliferation of Anaplasma phagocytophilum is promoted via modulation of endoplasmic reticulum stress signaling in host cells
Authors: Yoshikawa Yuko , Sugimoto Kei , Ochiai Yoshitsugu , Ohashi Norio
Published: January 2020

Anaplasma phagocytophilum, an obligate intracellular bacterium that propagates within host granulocytes, is considered to modify the host intracellular environment for pathogenesis. However, the mechanism(s) underlying such host modifications remain unclear. Here, we aimed to investigate the relation between A. phagocytophilum and endoplasmic reticulum (ER) stress in THP‐1 cells. A. phagocytophilum activated the three ER stress sensors: inositol‐requiring enzyme‐1 (IRE1), protein kinase RNA‐like endoplasmic reticulum kinase (PERK), and activating transcription factor‐6 (ATF6). IRE1 activation occurred immediately after host cell invasion by A. phagocytophilum; however, the activated IRE1‐induced splicing of X‐box‐binding protein 1 was not promoted during A. phagocytophilum infection. This suppression was sustained even after the doxycycline‐mediated elimination of intracellular A. phagocytophilum. IRE1 knockdown accelerated A. phagocytophilum‐induced apoptosis and decreased intracellular A. phagocytophilum. These data suggest that A. phagocytophilum utilizes IRE1 activation to promote its own intracellular proliferation. Moreover, PERK and ATF6 partially mediated A. phagocytophilum‐induced apoptosis by promoting the expression of CCAAT/enhancer‐binding protein homologous protein, which induces the transcription of several proapoptotic genes. Thus, A. phagocytophilum possibly manipulates the host ER stress signals to facilitate intracellular proliferation and infection of surrounding cells before/after host cell apoptosis.
Antibacterial effects of chitosan coating containing Mentha aquatica L. essence against Escherichia coli, Staphylococcus aureus and Listeria monocytogenes in Iranian white cheese
Authors: Hani Tabaie Zavareh Seyed Ahmad , Ardestani Fatemeh
Published: January 2020

The effect of a chitosan coating and Mentha aquatica L. essence on Iranian white cheese was investigated. Results showed 100% inhibition of Escherichia coli growth using 1.5% essence after 10 days. After 15 days of incubation, the Staphylococcus aureus population was reduced by 44.2%, 70.0%, and 88.5% using 0.5, 1.0 and 1.5% essence, respectively. After 15 days, Listeria monocytogenes growth was inhibited by 63.84%, 70.12%, and 85.9% using 0.5, 1.0, and 1.5% essence, respectively. Inhibition zone diameter studies also confirmed the antibacterial effects of applied coating against all the above‐mentioned bacteria in Iranian white cheese.
The Irish dairy industry – Recent history and strategy, current state and future challenges
Authors: Kelly Paidi , Shalloo Laurence , Wallace Michael , Dillon Pat
Published: January 2020

This study explores drivers and resulting changes in the structure and technical efficiency of Irish dairy farms from 2005 to 2018 (covering pre‐ and post‐milk quotas) during which milk production increased by 54%. Over this period, farm structure changed dramatically (fourfold increase in farmers milking >100 cows) and farmers improved technical efficiency and profitability and reduced the greenhouse gas emission intensity of milk produced. The impact of the adoption of key technologies at farm level and the contribution of strategic direction nationally (the Irish Government's Food Harvest 2020 Strategy) influencing this development are explored as are future sector challenges.
Local labour market competition and radical right voting: Evidence from France
Authors: BOLET DIANE
Published: January 2020

How do the economic effects of immigration affect radical right support? The evidence in support of the labour market competition theory — which posits that the economic threat posed by immigration to jobs and wages leads to radical right voting — has been mixed. On the one hand, individual‐level surveys underreport economic drivers because of social desirability bias. On the other hand, contextual studies show contradictory findings due to an over‐reliance on units of analysis that are too aggregated to meaningfully capture the competitive threat posed by immigrants. This paper identifies the influence of labour market competition on radical right voting at a local level in contexts where native workers are directly affected by the arrival of immigrants who have similar or higher skillsets. Using an original longitudinal dataset of fine‐grained municipal electoral, demographic and economic data from France over the 2002–2017 period, the paper provides empirical evidence of local contextual influences of economic competition between natives and immigrants of any skillset. Under local conditions of material deprivation, measured by the local unemployment rate, the effect of labour market competition on municipalities’ radical right vote share is amplified. Moreover, higher radical right support is observed in municipalities with a higher share of any one of the following groups: low‐skilled natives, medium‐skilled immigrants or high‐skilled immigrants. This supports the hypothesis that immigrants with higher qualifications are compelled to accept lower‐skilled jobs, and are thus perceived as a competitive threat to low‐skilled natives. By reconciling radical right contextual studies and research on the political economy of immigration policies, this paper highlights the importance of a local analysis in detecting the effect of labour market competition on radical right support. This paper also explains why some local areas are more prone to radical right support than others over time.
Genome‐wide association study for growth and fatness traits in Chinese Sujiang pigs
Authors: Xu P. , Ni L. , Tao Y. , Ma Z. , Hu T. , Zhao X. , Yu Z. , Lu C. , Zhao X. , Ren J.
Published: January 2020

Growth and fatness traits are complex and economically important traits in the pig industry. The molecular basis underlying porcine growth and fatness traits remains largely unknown. To uncover genetic loci and candidate genes for these traits, we explored the GeneSeek GGP Porcine 80K SNP chip to perform a GWAS for seven growth and fatness traits in 365 individuals from the Sujiang pig, a recently developed breed in China. We identified two, 17, one and 11 SNPs surpassing the suggestively significant threshold (P < 1.86 × 10−5) for body weight, chest circumference, chest width and backfat thickness respectively. Of these SNPs, 20 represent novel genetic loci, and five and four SNPs were respectively associated with chest circumference and backfat thickness at a genome‐wide significant threshold (P < 9.31 × 10−7). Eight SNPs had a pleiotropic effect on both chest circumference and backfat thickness. The most remarkable locus resided in a region between 72.95 and 76.27 Mb on pig chromosome 4, harboring a number of previously reported quantitative trait loci related to backfat deposition. In addition to two reported genes (PLAG1 and TAS2R38), we identified four genes including GABRB3, ZNF106, XKR4 and MGAM as novel candidates for body weight and backfat thickness at the mapped loci. Our findings provide insights into the genetic architecture of porcine growth and fatness traits and potential markers for selective breeding of Chinese Sujiang pigs.
Methamphetamine Use and Sexual Risk Behaviors among Men Who Have Sex With Men in a Mexico‐US Border City
Authors: Loza Oralia , Curiel Zuleika V. , Beltran Oscar , Ramos Rebeca
Published: January 2020

Background and Objectives

Methamphetamine (meth) use and its related risk behaviors for HIV among men who have sex with men (MSM) are a public health concern across the Mexico‐US border. This study aims to contribute to the limited literature of meth use and sexual risk behaviors among Latino MSM on the Mexico‐US border.

Methods

Data were drawn from the Meth Pilot Study (2014‐2015) among men who use meth (n = 100). Descriptive statistics and bivariate analysis comparing MSM to non‐MSM were conducted using Pearson’sχ2test, Fisher’s exact tests, and Mann‐WhitneyUtest; all tests were conducted using SPSS v.25.

Results

Most participants obtained meth in El Paso, Texas (87.2%), used meth orally (65.2%) or smoked (78.3%), and the most common reason for initiation was curiosity. Significant differences (P < .05) in meth use behaviors and sexual risk behaviors between MSM and non‐MSM who used meth included: median number of sex partners (7 vs 3), being penetrated anally by last sexual partner (31.6% vs 1.4%), and engaging in transactional sex ever (63.2% vs 9.6%) and past 12 months (52.6% vs 6.8%). Finally, rates of HIV positivity were higher among MSM than non‐MSM (10.5% vs 1.4%).

Discussion and Conclusions

Among men who use meth, MSM are engaging in higher HIV risk behaviors compared with non‐MSM. Understanding these risks could help identify candidates for pre‐exposure prophylaxis (PrEP) and evidence‐based substance use disorder treatment options.

Scientific Significance

This study reveals that Latino MSM who use meth is a high‐risk group for HIV and a need for tailored interventions. (Am J Addict 2020;29:111–119)
Systematic review with meta‐analysis: the risks of proton pump inhibitors during pregnancy
Authors: Li Cheng Mei , Zhernakova Alexandra , Engstrand Lars , Wijmenga Cisca , Brusselaers Nele
Published: January 2020

Background

There have been safety concerns considering long‐term proton pump inhibitor (PPI) use, also during pregnancy.

Aims

To assess the risk of adverse neonatal outcomes associated with maternal intake of PPIs by means of systematic review and meta‐analysis.

Methods

The systematic search included PubMed, Web of Science, Cochrane Database and Embase (inception until June 2019). All studies reporting ≥1 adverse pregnancy outcome comparing PPI users to non‐users. Histamine‐2 receptor antagonists (H2RA) were also compared to both non‐users and PPI users. Outcomes included congenital malformations, abortion, stillbirth, neonatal death, preterm birth, small for gestational age and low birth weight. Pooled odds ratios (OR) and 95% confidence intervals (CI) were obtained by random‐effects modelling. PROSPERO study‐protocol: CRD42018103320.

Results

In total, 26 observational studies (20 cohort, 6 case‐control studies) were identified, of which 19 assessed PPIs and 12 H2RA. PPI use was associated with an increased risk of congenital malformations (OR 1.28, 95% CI 1.09‐1.52), especially in case‐control studies (OR 2.04, 1.46‐2.86). No associations were found between H2RA and congenital malformations. No significant associations were found between PPI use and abortions, stillbirth, neonatal death, preterm birth and low‐birth weight, although H2RA use may be associated with an increased risk of preterm birth (OR 1.25, 95% CI 1.02‐1.56). Although statistical heterogeneity and the risk of bias were overall low, clinical heterogeneity, information and selection bias may be present in the individual studies.

Conclusions

This meta‐analysis suggests an association between maternal PPI use and congenital malformations in humans, yet power was insufficient to assess specific malformations and drugs.
Off‐clamp tumor excision using soft coagulation in laparoscopic and robotic partial nephrectomy
Authors: Yoshida Tetsuya , Okinaka Yuki , Tomita Keiji , Tsuru Teruhiko , Kageyama Susumu , Narita Mitsuhiro , Kawauchi Akihiro
Published: January 2020

Introduction

The aim of this study was to assess the perioperative outcomes of off‐clamp tumor excision using soft coagulation in laparoscopic and robotic partial nephrectomy.

Methods

We retrospectively analyzed the data from 78 patients who underwent minimally invasive partial nephrectomy, using soft coagulation, at the Shiga University of Medical Science, between September 2013 and April 2017. Tumor excision and hemostasis without renal arterial clamping was performed using soft coagulation. Collecting system repair and renorrhaphy with arterial clamping were carried out only if the collecting system had been opened.

Results

Forty‐three of the 78 patients underwent laparoscopic partial nephrectomy using soft coagulation and the other 35 patients underwent robotic partial nephrectomy using soft coagulation. The median estimated total blood loss was 73 (0‐1140) mL and no patient needed a blood transfusion. No cases featured postoperative hemorrhagic events. Six patients with urinary fistula needed prolonged ureteral stenting. The median percentage change of the estimated glomerular filtration rate was −7.2 at one to 3 months after surgery.

Conclusion

The off‐clamp soft coagulation technique in laparoscopic partial nephrectomy and robotic partial nephrectomy is a safe and feasible approach to excise kidney tumors. This procedure may reduce the incidence of perioperative hemorrhagic complications.
The potential function of endometrial‐secreted factors for endometrium remodeling during the estrous cycle
Authors: Billhaq Dody Houston , Lee Sang‐Hee , Lee Seunghyung
Published: January 2020

Uterine has a pivotal role in implantation and conceptus development. To prepare a conducive uterine condition for possibly new gestation during the estrous cycle, uterine endometrium undergoes dramatic remodeling. In addition, angiogenesis is an indispensable biological process of endometrium remodeling. Furthermore, essential protein expressions related to important biological processes of endometrium remodeling, which are vascular endothelial growth factor (VEGF), myoglobin (MYG), collagen type IV (COL4), fucosyltransferase IV (FUT4), and cysteine‐rich protein 2 (CRP2), were detected in the endometrial tissue reported in many previous studies and recently discovered in histotroph substrates during the estrous cycle. Those proteins, which are liable for provoking new vessel development, cell proliferation, cell adhesion, and cell migration, were expressed higher in the histotroph during the luteal phase than follicular phase. Histotroph proteins considerably contribute to endometrium remodeling during the estrous cycle. To that end, the following review will discuss and highlight the relevant information and evidence of the uterine fluid proteins as endometrial‐secreted factors that adequately indicate the potential role of the uterine secretions to be involved in the endometrial remodeling process.
Efficient recruitment of c‐FLIPL to the death‐inducing signaling complex leads to Fas resistance in natural killer‐cell lymphoma
Authors: Masuda Azuchi , Isobe Yasushi , Sugimoto Koichi , Yoshimori Mayumi , Arai Ayako , Komatsu Norio
Published: January 2020

Activation‐induced cell death (AICD) mediated by the Fas/Fas ligand (FasL) system plays a key role in regulating immune response. Although normal natural killer (NK) cells use this system for their homeostasis, malignant NK cells seem to disrupt the process. Extranodal NK/T‐cell lymphoma, nasal type (ENKL) is a rare but fatal disease, for which novel therapeutic targets need to be identified. We confirmed that ENKL‐derived NK cell lines NK‐YS and Hank1, and primary lymphoma cells expressed procaspase‐8/FADD‐like interleukin‐1β‐converting enzyme (FLICE) modulator and cellular FLICE‐inhibitory protein (c‐FLIP), along with Fas and FasL. Compared with Fas‐sensitive Jurkat cells, NK‐YS and Hank1 showed resistance to Fas‐mediated apoptosis in spite of the same expression levels of c‐FLIP and the death‐inducing signaling complex (DISC) formation. Unexpectedly, the long isoform of c‐FLIP (c‐FLIPL) was coimmunoprecipitated with Fas predominantly in both ENKL‐derived NK cell lines after Fas ligation. Indeed, c‐FLIPL was more sufficiently recruited to the DISC in both ENKL‐derived NK cell lines than in Jurkat cells after Fas ligation. Knockdown of c‐FLIPL per se enhanced autonomous cell death and restored the sensitivity to Fas in both NK‐YS and Hank1 cells. Although ENKL cells are primed for AICD, they constitutively express and efficiently utilize c‐FLIPL, which prevents their Fas‐mediated apoptosis. Our results show that c‐FLIPL could be a promising therapeutic target against ENKL.
Phenotypic shift of small intestinal intra-epithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential
Authors: Uhde M , Yu X , Bunin A , Brauner C , Lewis S K , Lebwohl B , Krishnareddy S , Alaedini A , Reizis B , Ghosh S , Green P H , Bhagat G
Published: January 2020

The small intestinal (SI) epithelium harbors a heterogeneous population of lymphocytes that mediate mucosal damage and repair in celiac disease (CD). The composition and roles of human proximal SI intra-epithelial innate lymphoid cells (ILCs), and their alterations in CD, are not well understood. We report that duodenal intra-epithelial ILCs predominantly consist of natural killer (NK)p44+CD127− cytotoxic ILC1s and NKp44−CD127+ helper ILC1s, while ILC3s only represent a minor population. In patients with newly diagnosed or active CD (ACD) and refractory CD type 1 (RCD I), the frequency of SI NKp44+ ILCs is decreased, with restoration of NKp44+ ILC frequency observed in patients adhering to a gluten-free diet who show evidence of mucosal healing. Moreover, the frequency of SI NKp44− ILCs is increased in ACD and RCD I patients and correlates with the severity of villous atrophy and epithelial damage, as assessed by serum levels of fatty acid binding protein 2 (FABP2). We show that the ILC alterations in CD represent a phenotypic shift of cytotoxic ILC1s rather than an increase in helper ILC1s or transdifferentiation of ILC1s to ILC3s, and activation-induced loss of NKp44 by cytotoxic ILC1s is associated with increased interferon (IFN)-γ expression and release of lytic granules. These findings suggest that intra-epithelial NKp44−CD127− cytotoxic ILC1s may contribute to mucosal damage in CD.
Further insights into the treatment of perineal hernia based on a the experience of a single tertiary centre
Authors: Blok R. D. , Brouwer T. P. A. , Sharabiany S. , Musters G. D. , Hompes R. , Bemelman W. A. , Tanis P. J.
Published: January 2020

Aim

There is little evidence concerning the optimal surgical technique for the repair of perineal hernia. This study aimed to report on the evolution of a technique for repair of perineal hernia by analysing the experience in a tertiary referral centre.

Method

This was a retrospective review of consecutive patients who underwent perineal hernia repair after abdominoperineal excision in a tertiary referral centre. The main study end‐points were rate of recurrent perineal hernia, perineal wound complications and related re‐intervention.

Results

Thirty‐four patients were included: in 18 patients a biological mesh was used followed by 16 patients who underwent synthetic mesh repair. Postoperative perineal wound infection occurred in two patients (11%) after biological mesh repair compared with four (25%) after synthetic mesh repair (P = 0.387). None of the meshes were explanted. Recurrent perineal hernia following biological mesh was found in 7 of 18 patients (39%) after a median of 33 months. The recurrence rate with a synthetic mesh was 5 of 16 patients (31%) after a median of 17 months (P = 0.642). Re‐repair was performed in four (22%) and two patients (13%), respectively (P = 0.660). Eight patients required a transposition flap reconstruction to close the perineum over the mesh, and no recurrent hernias were observed in this subgroup (P = 0.030). No mesh‐related small bowel complications occurred.

Conclusion

Recurrence rates after perineal hernia repair following abdominoperineal excision were high, and did not seem to be related to the type of mesh. If a transposition flap was added to the mesh repair no recurrences were observed, but this finding needs confirmation in larger studies.
Regulatory Affairs 101: Introduction to Expedited Regulatory Pathways
Authors: Cox Erica M. , Edmund Anita V. , Kratz Erica , Lockwood Sarah H. , Shankar Aishwarya
Published: January 2020

Developing a novel drug, including discovery, nonclinical toxicology studies, initial clinical trials, and thorough pivotal studies, may take many years. Once an applicant has generated this comprehensive body of data, the final step prior to regulatory approval is Health Authority review of the marketing authorization application. Review by regulatory authorities to evaluate whether the data support a positive benefit/risk profile takes many months, adding additional time before patients may access therapy. In this paper, we discuss the various opportunities the US Food and Drug Administration and the European Medicines Agency offer to expedite the drug development and regulatory approval timelines for drugs intended to treat serious diseases and unmet medical needs.
Extracorporeal photopheresis for graft‐vs‐host disease: A literature review and treatment guidelines proposed by the Nordic ECP Quality Group
Authors: Nygaard Marietta , Wichert Stina , Berlin Gösta , Toss Fredrik
Published: January 2020

Extracorporeal photopheresis (ECP) is one of the most used and established therapies for steroid‐refractory graft‐vs‐host disease (GvHD), with a good effect to side effect profile. In this review, we present a summary of present literature and provide evidence‐based treatment guidelines for ECP in GvHD. The guidelines constitute a consensus statement formed by the Nordic ECP Quality Group representing all ECP centres in the Nordic countries, and aims to facilitate harmonisation and evidence‐based practice. In developing the guidelines, we firstly conducted a thorough literature search of original articles and existing guidelines. In total, we identified 26 studies for ECP use in acute GvHD and 36 in chronic GvHD. The studies were generally small, retrospective and heterogeneous regarding patient characteristics, treatment schedule and outcome assessment. In general, a majority of patients achieved partial response or better, but response rates varied by the organs affected. Head‐to‐head comparisons to other treatment modalities were lacking. Overall, we consider the quality of evidence to be low–moderate (GRADE) and encourage future prospective multi‐armed trials to strengthen the present recommendations. However, despite limitations in evidence strength, standardised treatment schedules and regular follow‐up are imperative to ensure the best possible patient outcome.
Investigating cortical features of Sotos syndrome using mice heterozygous for Nsd1
Authors: Oishi Sabrina , Zalucki Oressia , Vega Michelle S. , Harkins Danyon , Harvey Tracey J. , Kasherman Maria , Davila Raul A. , Hale Lauren , White Melissa , Piltz Sandra , Thomas Paul , Burne Thomas H. J. , Harris Lachlan , Piper Michael
Published: January 2020

Sotos syndrome is a developmental disorder characterized by a suite of clinical features. In children, the three cardinal features of Sotos syndrome are a characteristic facial appearance, learning disability and overgrowth (height and/or head circumference > 2 SDs above average). These features are also evident in adults with this syndrome. Over 90% of Sotos syndrome patients are haploinsufficient for the gene encoding nuclear receptor‐binding Su(var)3‐9, Enhancer‐of‐zesteand Trithorax domain‐containing protein 1 (NSD1). NSD1 is a histone methyltransferase that catalyzes the methylation of lysine residue 36 on histone H3. However, although the symptomology of Sotos syndrome is well established, many aspects of NSD1 biology remain unknown. Here, we assessed the expression of Nsd1 within the mouse brain, and showed a predominantly neuronal pattern of expression for this histone‐modifying factor. We also generated a mouse strain lacking one allele of Nsd1 and analyzed morphological and behavioral characteristics in these mice, showing behavioral characteristics reminiscent of some of the deficits seen in Sotos syndrome patients.
The role of group dynamics in low‐achieving EFL students’ speaking development
Authors: Ben Maad Mohamed Ridha , Saadi Ibrahim
Published: January 2020

Exploring group dynamics in a foreign language classroom has not yet received ample consideration in mainstream research, notably their specified role in foreign language development. The study reported presently sought to document the particularity of this effect on an uncommonly chartered segment of the low‐achieving students in an intermediate‐level class. Following a time‐series design in which they performed watch‐and‐tell speaking tasks in a 14‐week experimental process, analysis considered audio‐recorded data from 15 participants after being transcribed and coded. While the results confirmed the positive relationship between the maturity of group processes and the participants’ willingness to communicate, they suggested slight to moderate improvement in their speaking skill development which in turn revealed a consistent use of processing patterns uncommon to group‐excepted students.
Update on the use of dapsone in dermatology
Authors: Ghaoui Nohra , Hanna Edith , Abbas Ossama , Kibbi Abdul‐Ghani , Kurban Mazen
Published: January 2020

Dapsone (4,4'‐diaminodiphenylsulfone) is the only remaining sulfone used in anthropoid therapeutics and is commercially available as an oral formulation, an inhaled preparation, and a 5% or 7.5% cream. Dapsone has antimicrobial effects stemming from its sulfonamide‐like ability to inhibit the synthesis of dihydrofolic acid. It also has anti‐inflammatory properties such as inhibiting the production of reactive oxygen species, reducing the effect of eosinophil peroxidase on mast cells and down‐regulating neutrophil‐mediated inflammatory responses. This allows for its use in the treatment of a wide variety of inflammatory and infectious skin conditions. Currently in dermatology, the US Food and Drug Administration (FDA)‐approved indications for dapsone are leprosy, dermatitis herpetiformis, and acne vulgaris. However, it proved itself as an adjunctive therapeutic agent to many other skin disorders. In this review, we discuss existing evidence on the mechanisms of action of dapsone, its FDA‐approved indications, off‐label uses, and side effects.
Krüppel homologue 1 interacts directly with Hairy and regulates ecdysis in the brown planthopper
Authors: Mao Y. , Li Y. , Gao H. , Lin X.
Published: January 2020

Juvenile hormone (JH) plays important roles in the growth and development of insects. JH and its receptor methoprene‐tolerant (Met) regulate the expression of transcription factors to control the transcription of downstream genes. The expression of Hairy (Hry) and Krüppel homologue 1 (Kr‐h1) is regulated by JH and JH receptors. Hry and Kr‐h1 are both crucial in mediating JH signalling. However, whether they interact at the gene level in regulating metamorphosis and whether they interact physically at the protein level remain unknown. We used co‐immunoprecipitation, glutathione S‐transferase pull‐down and RNA interference (RNAi) approaches to study the genetic and biochemical interactions of the two proteins Hry and Kr‐h1. The results showed that brown planthopper (Nilaparvata lugens) Hry and Kr‐h1 interact directly: Hry binds to the N‐terminal of Kr‐h1, which includes five zinc‐finger domains. The RNAi experiment showed that downregulation of Hry reduced the ratio of ecdysis failure caused by knockdown of Kr‐h1, indicating that the downregulation of Hry might mitigate ecdysis failure via the downregulation of Kr‐h1. The expression of Hry increased significantly when Kr‐h1 was downregulated, whereas it did not change significantly when both were downregulated. Our results suggest that the binding of Hry protein with Kr‐h1 prevents the N‐terminal five zinc‐finger domains from binding with DNA, which in turn inactivates the transcription activator or inhibitor function of Kr‐h1. Hry could possibly be used as a target for pesticide applications in the future.
Preventive use of non‐invasive ventilation is associated with reduced risk of extubation failure in patients on mechanical ventilation for more than 7 days: a propensity‐matched cohort study
Authors: Jiang Jinyue , Pan Jianxin
Published: January 2020

Background

Extubation failure (EF) is high in patients on mechanical ventilation for more than 7 days. However, strategies to prevent EF in this population are lacking.

Aims

To evaluate the efficacy of preventive use of noninvasive ventilation in patients on mechanical ventilation for more than 7 days.

Methods

We performed a retrospective study in an intensive care unit of a teaching hospital. We enrolled patients who received mechanical ventilation for more than 7 days and successfully completed a weaning trial. After extubation, patients who immediately received non‐invasive ventilation (NIV) were classified as the NIV group, and those who received conventional oxygenation therapy only were classified as the usual care group.

Results

We enrolled 95 patients in the NIV group and 61 patients in the usual care group. NIV is associated with reduced risk of EF compared to usual care both 72 h following extubation (11.6% vs 32.8%, P < 0.01, for the overall cohort; 8.6% vs 42.9%, P < 0.01, for the propensity‐matched cohort) and 7 days following extubation (25.3% vs 45.9%, P < 0.01, for the overall cohort; 28.6% vs 51.4%, P = 0.09, for the propensity‐matched cohort). Within 7 days of extubation, the NIV group had a lower proportion of EF than the controls (log rank test: P < 0.01 and P = 0.02 for the overall and propensity‐matched cohorts, respectively).

Conclusions

In patients on mechanical ventilation for more than 7 days, preventive use of NIV is associated with a reduction in EF.
Comparison of the quick Sepsis‐related Organ Failure Assessment and adult sepsis pathway in predicting adverse outcomes among adult patients in general wards: a retrospective observational cohort study
Authors: Li Ling , Rathnayake Kasun , Green Malcolm , Shetty Amith , Fullick Mary , Walter Scott , Middleton‐Rennie Catriona , Meller Michael , Braithwaite Jeffrey , Lander Harvey , Westbrook Johanna I.
Published: January 2020

Background

Quick Sepsis‐related Organ Failure Assessment (qSOFA) is recommended for use by the most recent international sepsis definition taskforce to identify suspected sepsis in patients outside the intensive care unit (ICU) at risk of adverse outcomes. Evidence of its comparative effectiveness with existing sepsis recognition tools is important to guide decisions about its widespread implementation.

Aim

To compare the performance of qSOFA with the adult sepsis pathway (ASP), a current sepsis recognition tool widely used in NSW hospitals and systemic inflammatory response syndrome criteria in predicting adverse outcomes in adult patients on general wards.

Methods

A retrospective observational cohort study was conducted which included all adults with suspected infections admitted to a Sydney teaching hospital between December 2014 and June 2016. The primary outcome was in‐hospital mortality with two secondary composite outcomes.

Results

Among 2940 patients with suspected infection, 217 (7.38%) died in‐hospital and 702 (23.88%) were subsequently admitted to ICU. The ASP showed the greatest ability to correctly discriminate in‐hospital mortality and secondary outcomes. The area under the receiver‐operating characteristic curve for mortality was 0.76 (95% confidence interval (CI): 0.74–0.78), compared to 0.64 for the qSOFA tool (95% CI: 0.61–0.67, P < 0.0001). Median time from the first ASP sepsis warning to death was 8.21 days (interquartile range (IQR): 2.29–16.75) while it was 0 days for qSOFA (IQR: 0–2.58).

Conclusions

The ASP demonstrated both greater prognostic accuracy and earlier warning for in‐hospital mortality for adults on hospital wards compared to qSOFA. Hospitals already using ASP may not benefit from switching to the qSOFA tool.
Transvenous management of cardiac implantable electronic device late lead perforation
Authors: Jessel Peter M. , Yadava Mrinal , Nazer Babak , Dewland Thomas A. , Miller Jared , Stecker Eric C. , Bhamidipati Castigliano M. , Song Howard K. , Henrikson Charles A.
Published: January 2020

Introduction

Late lead perforation (LLP), defined as perforation ≥30 days from cardiac implantable electronic device implant, is a rare diagnosis and little data exist regarding management practices and outcomes. The purpose of this study was to evaluate the occurrence, safety, and efficacy of transvenous management of clinically significant LLP.

Methods

The electronic medical records of a single‐center tertiary hospital were reviewed for all patients who were referred for LLP or its sequelae.

Results

Eleven consecutive patients were identified from October 2011 to December 2018 with clinically significant LLP. Patients most often presented with pericardial symptoms with the exception of one asymptomatic patient. The median time from lead implant to intervention for LLP was 246 days. Nine patients were managed with an initial transvenous approach, with one requiring sternotomy (lead 6.3 years old). Two patients had a surgical approach, one performed at an outside hospital with subsequent death and another had a mini‐thoracotomy, but the lead was removed percutaneously with no surgical repair. In this small cohort, there was no association between the lead extending beyond the parietal pericardium and surgical repair (P = .99).

Conclusion

Our single‐center experience suggests that LLP can be initially managed with a cautious transvenous approach in most patients, but intraprocedural ultrasound for pericardial monitoring and a rescue plan with immediate surgical back up is mandatory.