bluuebunny/crossref_metadata_2025 huggingface dataset:
Coexistence of JAK2 or CALR mutation is a rare but clinically important event in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors
Authors: Lewandowski K. , Gniot M. , Wojtaszewska M. , Kanduła Z. , Becht R. , Paczkowska E. , Mędraś E. , Wasilewska E. , Iwoła M.
Published: March 2018

Introduction

There are 7 designated conditions under the category of myeloproliferative neoplasms (MPN), including chronic myelogenous leukemia (CML) and classical MPN, that is, polycythemia vera (PV), essential thrombocythaemia (ET), and primary myelofibrosis (PMF). Recently, reports about Philadelphia and JAK2 V617F‐positive MPN cases have been described in literature. The coexistence of different molecular defects may change the clinical and laboratory manifestation of MPN and may result in an inappropriate interpretation of the response to treatment with tyrosine kinase inhibitors in CML patients.

Methods

The morphological, cytogenetic, and molecular genetic data from a retrospective analysis of 592 adult patients aged 18‐86 years diagnosed with CML were analyzed.

Results

In 5 CML patients, the presence of JAK2 V617F or CALR mutation was confirmed. Three of 4 TKI‐treated patients did not reach complete hematologic response due to the persistence of thrombocytosis and/or splenomegaly. In all of them (in 3 with JAK2 V617F mutation and 1 with CALR mutation), thrombocytosis was present at the time when complete cytogenetic response was documented. In 3 out of 4 reported CML patients, thrombocytosis and/or splenomegaly were still present even at the time when deep molecular response was reached.

Conclusion

In our opinion, a detailed evaluation and appropriate interpretation of clinical and laboratory data in such a category of patients seem to be extremely important, especially when a decision about the TKI change due to therapy failure is considered.
Des relations professionnelles transnationales à la négociation collective transfrontière
Authors: LUTERBACHER Urs , PROSSER Andrew , PAPADAKIS Konstantinos
Published: March 2018

Face à la mondialisation, les fédérations syndicales internationales et les entreprises multinationales ont cherché à protéger leurs intérêts par des «accords‐cadres internationaux», ou ACI. En modélisant les processus de négociation sous‐jacents, les auteurs montrent que ces accords n'aboutissent que si les deux partenaires présentent une aversion pour le risque et qu'ils tendent à favoriser celle des parties chez qui cette aversion est moins prononcée, les multinationales en l'occurrence, aux dépens des travailleurs. Les choses pourraient évoluer cependant si les syndicats parviennent, par une action transnationale, à déstabiliser les multinationales en menaçant leur réputation, rapprochant le niveau d'aversion pour le risque des deux interlocuteurs.
Normes, théorie des jeux et pratiques participatives: le poids réel des travailleurs dans les économies libérales
Authors: DOBBINS Tony , DUNDON Tony , CULLINANE Niall , HICKLAND Eugene , DONAGHEY Jimmy
Published: March 2018

Les auteurs analysent l'effet de la directive européenne relative à l'information et à la consultation des travailleurs sur les pratiques participatives en entreprise au Royaume‐Uni et en Irlande. Dans une analyse conceptuelle et empirique, qui fait appel à la théorie des jeux, ils formulent trois hypothèses explicatives, qu'ils cherchent à vérifier avec des données qualitatives recueillies auprès de seize entreprises. La démonstration permet de comprendre pourquoi la coopération, gage de gains mutuels, n'est pas la solution qui l'emporte dans les pays examinés, et elle nous en dit un peu plus sur l'effet des normes sur la gestion participative dans les économies de marché libérales.
Relation entre l'emploi des jeunes et l'emploi des seniors dans vingt pays de l'OCDE
Authors: JI Eun Jeong
Published: March 2018

S'appuyant sur la thèse selon laquelle il existerait un volume fixe d'emplois dans l'économie, beaucoup de pays de l'OCDE ont cherché à lutter contre le chômage, en augmentation depuis les années 1970, par des dispositifs favorisant les cessations d'activité anticipées. Or les études à l'échelle de l'OCDE font apparaître en réalité une corrélation positive entre l'emploi des jeunes et celui des travailleurs âgés. Cependant, comme la plupart des auteurs estiment des effets moyens, on dispose de relativement peu d'informations sur l'hétérogénéité de ce lien. L'auteure tente de combler cette lacune en étudiant cette hétérogénéité dans vingt pays de l'OCDE.
Maternal Mentalization and Behavior Under Stressful Contexts: The Moderating Roles of Prematurity and Household Chaos
Authors: Yatziv Tal , Gueron‐Sela Noa , Meiri Gal , Marks Kayla , Atzaba‐Poria Naama
Published: March 2018

This study examines the links between online maternal mentalization during mother–infant interaction, maternal sensitivity, and family triadic interaction while considering the cumulative role of two stressful contexts (cumulative stressful contexts): premature birth (a child‐driven stressful context) and household chaos (an environment‐driven stressful context). Two moderation models were tested on a sample of 134 families with 6‐month‐old infants (77 low‐risk preterm, 57 full‐term). Cumulative stressful contexts mitigated the relations between maternal mentalization and behavior, such that online maternal mentalization during mother–infant interaction was related to both maternal sensitivity and the quality of family triadic interaction under low cumulative stressful contexts, but not under high cumulative stressful contexts. Implications for understanding the influence of online maternal mentalization on maternal sensitivity and the family triad are discussed.
Impact of resilience and job involvement on turnover intention of new graduate nurses using structural equation modeling
Authors: Yu Mi , Lee Haeyoung
Published: March 2018

Aims

Nurses' turnover intention is not just a result of their maladjustment to the field; it is an organizational issue. This study aimed to construct a structural model to verify the effects of new graduate nurses' work environment satisfaction, emotional labor, and burnout on their turnover intention, with consideration of resilience and job involvement, and to test the adequacy of the developed model.

Methods

A cross‐sectional study and a structural equation modelling approach were used. A nationwide survey was conducted of 371 new nurses who were working in hospitals for ≤18 months between July and October, 2014.

Results

The final model accounted for 40% of the variance in turnover intention. Emotional labor and burnout had a significant positive direct effect and an indirect effect on nurses' turnover intention. Resilience had a positive direct effect on job involvement. Job involvement had a negative direct effect on turnover intention. Resilience and job involvement mediated the effect of work environment satisfaction, emotional labor, and burnout on turnover intention.

Conclusion

It is important to strengthen new graduate nurses' resilience in order to increase their job involvement and to reduce their turnover intention.
Longitudinal Improvement in Periodontal Parameters between RPD Abutment Teeth with Direct and Indirect Retainers, after Periodontal Therapy
Authors: Almeida Mariana Linhares , Tôrres Ana Clara Soares de Paiva , de Oliveira Kleiton Clécio , Calderon Patrícia dos Santos , Carreiro Adriana da Fonte Porto , Gurgel Bruno César de Vasconcelos
Published: March 2018

Purpose

To evaluate the effect of basic periodontal treatment on clinical periodontal parameters associated with abutment teeth of patients with mandibular Kennedy class I removable partial dentures (RPD) 18 months after treatment.

Materials and Methods

Thirty patients with periodontal disease were treated and evaluated according to the following periodontal parameters: visible plaque index (VPI), bleeding on probing (BOP), probing depth (PD), gingival recession (GR), clinical attachment loss (CAL), and keratinized mucosa (KM). These parameters were compared between abutment teeth with direct and indirect retainers at baseline, and after 6 and 18 months. Data were analyzed by Friedman Test and Wilcoxon Test for all variables.

Results

Most patients (n = 26; 86.7%) included in the study were female and had a mean age of 61 years (±7.54). Results showed that VPI and BOP decreased over time, and that VPI values were higher in abutment teeth with direct retainers (p = 0.001). There was a reduction in PD after 6 months, which was maintained up to 18 months. In general, abutment teeth with direct retainers had significantly higher values for PD, GR, and CAL (p = 0.029). Data also indicated that the parameters for VPI, BOP, and PD improved; however, abutment teeth with direct retainers presented smaller improvements, compared with abutment teeth with indirect retainers, which presented significant improvements for almost all variables.

Conclusion

Periodontal treatment and oral hygiene care of patients were adequate for maintenance of adequate periodontal conditions, regardless of the use of prostheses.
Auricular Retentive Prosthetic Conformer Post Brent's Stage III Surgery in Microtia Repair: A Clinical Report
Authors: Lingeshwar D. , Appadurai R. , Challa Padmaja , Sswedheni S. U.
Published: March 2018

Auricular reconstruction is an interdisciplinary approach where multiple specialties play a vital role in the treatment provided to the patient. This article provides a comprehensive interpretation of the process carried out for the fabrication of a custom‐made prosthetic conformer for the management of postoperative contraction of a skin graft after ear reconstruction surgery—Brent stage III. The prosthesis is used as a precautionary measure and is simple, effective, and economical.
The Development of Nonanatomic Denture Occlusion: Part III
Authors: Engelmeier Robert L.
Published: March 2018

Part III of this four‐part series about nonanatomic denture tooth development traces the evolution of this movement from the mid‐1930s through the World War II era up to the early 1950s. By this time, the general preference for posterior denture occlusion had shifted from anatomic to nonanatomic teeth, and all the major denture tooth manufacturing companies listed at least one nonanatomic design in their inventories.
Multisensory Representation of Gender in Infants: An Eye‐Tracking Study
Authors: Méary David , Jaggie Carole , Pascalis Olivier
Published: March 2018

Visual and auditory information jointly contribute to face categorization processes in humans, and gender is a socially relevant multisensory category specified by faces and voices that is detected early in infancy. We used an eye tracker to study how gender coherence in audio and visual modalities influence face scanning in 9‐ to 12‐month‐old infants and in adults. While viewing dynamic faces, infants attended to a speaker's mouth region to a greater extent than adults, regardless of speech, which was mostly due to an increase in mean fixation durations. However, the time course of attending to eye and mouth regions showed similarities in adults and infants. Face–voice congruence for gender appeared to have little effect on measures of face scanning. Overall, results suggested that 9‐ to 12‐month‐old infants give more weight to the processing of a speaker's mouth compared to adults but that infants already have an adult‐like face‐scanning strategy.
Mammals and meaningful taxonomic units: the debate about species concepts and conservation
Authors: Zachos Frank E.
Published: March 2018

Mammalian taxonomy based on the diagnosability version of the Phylogenetic Species Concept has recently been declared the only sound approach to mammalian classification. In this article, based on the underlying evolutionary ontology of species taxa, I explain the fallacy of these arguments and hold that in a ‘grey area’ after lineage sundering, completely objective species delimitation is impossible, making both lumping and splitting equally correct or incorrect. As a consequence, we may have to get used to the idea that described species are often a poor guide to the delineation of meaningful taxonomic units for conservation.
Standardized training for AVT pacing in paediatric patients with postoperative junctional ectopic tachycardia
Authors: Entenmann Andreas , Dittrich Susann , Hessling Vera , Niederwanger Christian , Cortina Gerard , Michel Miriam
Published: March 2018

Background

Junctional ectopic tachycardia is a serious complication of surgery for paediatric congenital heart disease. R‐wave synchronized atrial (AVT) pacing, an innovative temporary pacing technique, restores atrioventricular synchrony in these patients. The method is highly effective but technically complex. A standardized training model exists for doctors but not for paediatric intensive care nurses.

Aims

This study seeks to evaluate whether a standardized programme involving simulation and vignettes increases knowledge of AVT pacing and accuracy of its documentation, as well as recognition and management of specific complications.

Study design

This study was an experimental simulation test with before and after descriptive evaluation.

Methods

A custom‐made simulation model was used in combination with standardized training. Before and after training, 10 paediatric nurse specialists were asked to document pacing, to identify complications and to intervene as necessary. Four clinical scenarios were presented: effective AVT pacing, ineffective AVT pacing, pacing with narrow interval between atrial pacing and ventricular sensing and pacemaker‐induced tachycardia. Identification and management of complications were evaluated using a 3‐point scale.

Results

Training improved the quality of documentation and complication management. At outset, documentation by 1 of 10 participants was completely correct, and after training, documentation by 8 of 10 participants was completely correct.

Before training, 30% of interpretations of the four presented clinical scenarios were correct (12/40) versus 83% (33/40) after training. The decision to notify a doctor of a complication was correct in 83% (33/40) before versus 95% (38/40) after the training.

Conclusion

Standardized simulation training improves quality and safety in AVT pacing, with more accurate documentation of the pacing mode and better recognition and management of specific complications during pacing.

Relevance to clinical practice

AVT pacing should be performed in conjunction with standardized simulation training in paediatric cardiac intensive care units.
Music training and child development: a review of recent findings from a longitudinal study
Authors: Habibi Assal , Damasio Antonio , Ilari Beatriz , Elliott Sachs Matthew , Damasio Hanna
Published: March 2018

Evidence suggests that learning to play music enhances musical processing skills and benefits other cognitive abilities. Furthermore, studies of children and adults indicate that the brains of musicians and nonmusicians are different. It has not been determined, however, whether such differences result from pre‐existing traits, musical training, or an interaction between the two. As part of an ongoing longitudinal study, we investigated the effects of music training on children's brain and cognitive development. The target group of children was compared with two groups of children, one involved in sports and another not enrolled in any systematic afterschool training. Two years after training, we observed that children in the music group had better performance than comparison groups in musically relevant auditory skills and showed related brain changes. For nonmusical skills, children with music training, compared with children without music or with sports training, showed stronger neural activation during a cognitive inhibition task in regions involved in response inhibition despite no differences in performance on behavioral measures of executive function. No such differences were found between music and sports groups. We conclude that music training induces brain and behavioral changes in children, and those changes are not attributable to pre‐existing biological traits.
Up‐regulation of GhTT2‐3A in cotton fibres during secondary wall thickening results in brown fibres with improved quality
Authors: Yan Qian , Wang Yi , Li Qian , Zhang Zhengsheng , Ding Hui , Zhang Yue , Liu Housheng , Luo Ming , Liu Dexin , Song Wu , Liu Haifeng , Yao Dan , Ouyang Xufen , Li Yaohua , Li Xin , Pei Yan , Xiao Yuehua
Published: March 2018

Brown cotton fibres are the most widely used naturally coloured raw materials for the eco‐friendly textile industry. Previous studies have indicated that brown fibre pigments belong to proanthocyanidins (PAs) or their derivatives, and fibre coloration is negatively associated with cotton productivity and fibre quality. To date, the molecular basis controlling the biosynthesis and accumulation of brown pigments in cotton fibres is largely unknown. In this study, based on expressional and transgenic analyses of cotton homologs of ArabidopsisPA regulator TRANSPARENT TESTA 2 (TT2) and fine‐mapping of the cotton dark‐brown fibre gene (Lc1), we show that a TT2 homolog, GhTT2‐3A, controls PA biosynthesis and brown pigmentation in cotton fibres. We observed that GhTT2‐3A activated GhbHLH130D, a homolog of ArabidopsisTT8, which in turn synergistically acted with GhTT2‐3A to activate downstream PA structural genes and PA synthesis and accumulation in cotton fibres. Furthermore, the up‐regulation of GhTT2‐3A in fibres at the secondary wall‐thickening stage resulted in brown mature fibres, and fibre quality and lint percentage were comparable to that of the white‐fibre control. The findings of this study reveal the regulatory mechanism controlling brown pigmentation in cotton fibres and demonstrate a promising biotechnological strategy to break the negative linkage between coloration and fibre quality and/or productivity.
The rice terpene synthase gene OsTPS19 functions as an (S)‐limonene synthase in planta, and its overexpression leads to enhanced resistance to the blast fungus Magnaporthe oryzae
Authors: Chen Xujun , Chen Hao , Yuan Joshua S. , Köllner Tobias G. , Chen Yuying , Guo Yufen , Zhuang Xiaofeng , Chen Xinlu , Zhang Yong‐jun , Fu Jianyu , Nebenführ Andreas , Guo Zejian , Chen Feng
Published: March 2018

Rice blast disease, caused by the fungus Magnaporthe oryzae, is the most devastating disease of rice. In our ongoing characterization of the defence mechanisms of rice plants against M. oryzae, a terpene synthase gene OsTPS19 was identified as a candidate defence gene. Here, we report the functional characterization of OsTPS19, which is up‐regulated by M. oryzae infection. Overexpression of OsTPS19 in rice plants enhanced resistance against M. oryzae, while OsTPS19 RNAi lines were more susceptible to the pathogen. Metabolic analysis revealed that the production of a monoterpene (S)‐limonene was increased and decreased in OsTPS19 overexpression and RNAi lines, respectively, suggesting that OsTPS19 functions as a limonene synthase in planta. This notion was further supported by in vitro enzyme assays with recombinant OsTPS19, in which OsTPS19 had both sesquiterpene activity and monoterpene synthase activity, with limonene as a major product. Furthermore, in a subcellular localization experiment, OsTPS19 was localized in plastids. OsTPS19 has a highly homologous paralog, OsTPS20, which likely resulted from a recent gene duplication event. We found that the variation in OsTPS19 and OsTPS20 enzyme activities was determined by a single amino acid in the active site cavity. The expression of OsTPS20 was not affected by M. oryzae infection. This indicates functional divergence of OsTPS19 and OsTPS20. Lastly, (S)‐limonene inhibited the germination of M. oryzae spores in vitro. OsTPS19 was determined to function as an (S)‐limonene synthase in rice and plays a role in defence against M. oryzae, at least partly, by inhibiting spore germination.
It's not you, it's them: Social influences on trust propensity and trust dynamics
Authors: Baer Michael D. , Matta Fadel K. , Kim Ji Koung , Welsh David T. , Garud Niharika
Published: March 2018

Scholars agree that trust primarily has two bases: trustworthiness—the extent to which a trustee is competent, honest, and has goodwill toward the trustor—and trust propensity—a stable trait reflecting the trustor's generalized belief that others can be trusted. Due to this trait characterization, the literature has largely reached a consensus that trust propensity is only an important base of trust in the earliest stage of a relationship—before information on trustworthiness has been gathered. Additionally, the trait conceptualization of trust propensity inhibits it from being modeled as an explanatory mechanism. Drawing on accessibility theory, a theory of trait activation, we argue that trust propensity has state‐like characteristics that are “activated” by the daily treatment an employee receives from coworkers. Our model highlights that the social context—predominantly ignored in prior trust research because of its lack of relevance to dyadic perceptions of trustworthiness—can have a substantial impact on dyadic trust. Across two multisource experience sampling methodology studies, we provide evidence that state trust propensity transmits the effects of citizenship and deviance received to trust in a focal coworker, whether that focal coworker is a source of that treatment or not. We also address how general levels of workplace unfairness—a between‐person construct—influence these dynamics. We discuss the theoretical and practical implications of these within‐person dynamics for fostering trust within organizations.
Quantitative Uncertainty Analysis for a Weed Risk Assessment System
Authors: Caton Barney P. , Koop Anthony L. , Fowler Larry , Newton Leslie , Kohl Lisa
Published: March 2018

Weed risk assessments (WRA) are used to identify plant invaders before introduction. Unfortunately, very few incorporate uncertainty ratings or evaluate the effects of uncertainty, a fundamental risk component. We developed a probabilistic model to quantitatively evaluate the effects of uncertainty on the outcomes of a question‐based WRA tool for the United States. In our tool, the uncertainty of each response is rated as Negligible, Low, Moderate, or High. We developed the model by specifying the likelihood of a response changing for each uncertainty rating. The simulations determine if responses change, select new responses, and sum the scores to determine the risk rating. The simulated scores reveal potential variation in WRA risk ratings. In testing with 204 species assessments, the ranges of simulated risk scores increased with greater uncertainty, and analyses for most species produced simulated risk ratings that differed from the baseline WRA rating. Still, the most frequent simulated rating matched the baseline rating for every High Risk species, and for 87% of all tested species. The remaining 13% primarily involved ambiguous Low Risk results. Changing final ratings based on the uncertainty analysis results was not justified here because accuracy (match between WRA tool and known risk rating) did not improve. Detailed analyses of three species assessments indicate that assessment uncertainty may be best reduced by obtaining evidence for unanswered questions, rather than obtaining additional evidence for questions with responses. This analysis represents an advance in interpreting WRA results, and has enhanced our regulation and management of potential weed species.
A generalized Okun's Law: Uncovering the myth of China's labor market resilience
Authors: Liu Xiaoguang , Lam Raphael , Schipke Alfred , Shen Guangjun
Published: March 2018

A stable labor market is a policy priority for most countries, especially after the burst of the global financial crisis. Unlike most countries, the labor market in China appears to be holding up well, despite sharp slowdown in economic growth. This paper argues that there are underlying fundamental mechanisms that help explain the resilience of China's labor market. The key to understanding labor market dynamics in China is that rural‐to‐urban migrant flows are more sensitive to growth than urban workers in the process of fast urbanization, which serves as a main shock absorber to buffer employment against adverse shocks. Therefore, we propose a generalized Okun's Law (GOL) that incorporates migrant flows with unemployment rates to capture the relation between labor market dynamics and economic cycles. The original Okun's Law can be regarded as a special case of the GOL for developed countries that have already completed urbanization. Conducting empirical analysis with both China's national‐ and city‐level data and cross‐country panel data, we find strong evidence supporting the GOL theory. Findings in the paper have implications for a deeper understanding of the wisdom of Okun's Law and its application in labor market policies.
Interactive value‐based curriculum: a pilot study
Authors: Bowman Peterson Jill M , Duffy Briar , Duran Alisa , Gladding Sophia P
Published: March 2018

Background

Current health care costs are unsustainable, with a large percentage of waste attributed to doctor practices. Medical educators are developing curricula to address value‐based care (VBC) in education. There is, however, a paucity of curricula and assessments addressing levels higher than ‘knows’ at the base of Miller's pyramid of assessment. Our objective was to: (1) teach residents the principles of VBC using active learning strategies; and (2) develop and pilot a tool to assess residents’ ability to apply principles of VBC at the higher level of ‘knows how’ on Miller's pyramid.

Methods

Residents in medicine, medicine–paediatrics and medicine–dermatology participated in a 5‐week VBC morning report curriculum using active learning techniques. Early sessions targeted knowledge and later sessions emphasised the application of VBC principles.

Medical educators are developing curricula to address value‐based care in education

Results

Thirty residents attended at least one session and completed both pre‐ and post‐intervention tests, using a newly developed case‐based assessment tool featuring a ‘waste score’ balanced with ‘standard of care’. Residents, on average, reduced their waste score from pre‐intervention to post‐intervention [mean 8.8 (SD 6.3) versus mean 4.7 (SD 4.6), p = 0.001]. For those who reduced their waste score, most maintained or improved their standard of care.

Discussion

Our results suggest that residents may be able to decrease health care waste, with the majority maintaining or improving their management of care in a case‐based assessment after participation in the curriculum. We are working to further incorporate VBC principles into more morning reports, and to develop further interventions and assessments to evaluate our residents at higher levels on Miller's pyramid of assessment.
A RHAG point mutation selectively disrupts Rh antigen expression
Authors: Mu S. , Cui Y. , Wang W. , Wang L. , Xu H. , Zhu O. , Zhu D.
Published: March 2018

Objectives

The aim of this study was to characterise a novel mutation in the gene encoding RhAG in order to elucidate a molecular mechanism for Rh antigen expression and spherocytosis.

Background

Rhesus‐associated glycoprotein (RhAG) is critical for maintaining the structure and stability of erythrocytes. Single missense mutations in the gene encoding RhAG are sufficient to induce spherocytosis and deficiencies in Rh complex formation. We report a novel missense mutation that incompletely disrupts Rh antigen expression and selectively knocks out RhD antigen expression.

Methods

Blood samples were taken from a 38‐year‐old male, his brother, his wife and his daughter in Xi'an, China. To detect the proband's RhAG and D antigen expression, the RBC were stained with anti‐D and anti‐RhAG and analysed by flow cytometry. Red blood cell morphology was detected with atomic force microscopy (AFM). Genomic DNA was isolated from whole blood samples, and the RHD, RHCE and RHAG alleles were sequenced and analysed. The mutation was mapped onto a predicted crystal structure of RhAG by the I‐TASSER server and visualised using PyMOL.

Results

Morphological testing by AFM found clear evidence of spherocytosis in the proband's erythrocytes. RHAG gene sequencing identified the mutation at sequence 236G > A, resulting in a serine to asparagine substitution at residue 79 (S79N). Family survey indicated that inheriting this allele is necessary and sufficient to cause the condition. Mapping the mutation onto a predicted crystal structure of RhAG revealed the proximity of the mutation to the critical structural elements of the protein.

Conclusions

A novel RHAG mutation significantly lowers RhAG antigen expression and antigen‐mediated agglutination intensity.
Does the tumour microenvironment alter tumorigenesis and clinical response in transmissible venereal tumour in dogs?
Authors: Ballestero Fêo H. , Montoya Flórez L. , Yamatogi R. S. , Prado Duzanski A. , Araújo J. P. , Oliveira R. A. , Rocha N. S.
Published: March 2018

The canine transmissible venereal tumour (CTVT) is a transmissible cancer that is spread naturally between dogs, with the ability to develop and evade the immune system, despite strict immune surveillance of the host. Furthermore, molecular signalling between cells of the immune system and the tumour microenvironment appear to influence the behaviour and development of the tumour. Thus, this study aimed to quantify the expression of genes related to the immune system such as IL‐6, IFN‐γ, and TGF‐β, as well as angiogenic factors (VEGF, CXCR4), in CTVT cells in vivo and in vitro (primary culture), correlating with the clinical response of the animals treated with vincristine. As expected, the most prevalent subtype was plasmacytoid cells, although lymphocytic cells were also found, indicating the possibility of polyclonality. When we compared the gene expressions of IFN‐γ and IL‐6, we mostly found low expression, concluding that MHC expression was probably not occurring in tumour cells, and no activation of immune cells to eliminate the tumour. The TGF‐β gene was normal in the majority of animals but demonstrated decreased expression in vincristine resistant animals, leading to the hypothesis that the concentration of tumour‐derived TGF‐β was affecting and even suppressing the real TGF‐β expression, favouring tumour proliferation and progression in these cases. VEGF expression was extremely high, demonstrating its angiogenic role in tumour growth, while CXCR4 was decreased, possibly because of CTVT’s low metastatic potential. Thus, we concluded that the tumour microenvironment, together with the immune system of the host, influences CTVT, presumably altering its tumorigenesis and the animal’s clinical response to treatment.
How different animal models help us understand TRALI
Authors: Fung Y. L. , Tung J.P.
Published: March 2018

Transfusion‐related acute lung injury (TRALI) is still one of the leading causes of transfusion‐associated mortality, despite increased awareness and the implementation of various mitigation strategies. TRALI may be either antibody or non‐antibody mediated. Understanding the underlying mechanism through clinical cases has been challenging because of the low and unpredictable incidence. Thus, animal models provide an important tool for investigating the mechanism of TRALI in a controlled and systematic fashion. One of the earliest animal models, an ex vivo rabbit lung model, revealed the role of anti‐5b (anti‐HNA‐3a) and granulocytes. In vivo models with mice, rats and pig models have provided further insights into the mechanisms of antibody‐mediated TRALI. There is evidence for contributions from neutrophils, neutrophil extracellular traps, platelets, lymphocytes, monocytes and endothelial cells. Elevated levels of C‐reactive proteins and cardiopulmonary bypass may predispose to TRALI, while protective roles have been identified with lymphocytes, T‐regulatory cells and dendritic cells. Mouse models have shown that IL‐10 infusion protects from TRALI if administered prophylactically and successfully treats TRALI reaction if administered therapeutically. Silliman et al. introduced the non‐immune mechanism of TRALI with rat models, and since then, there have been sheep and pig models. Non‐immune animal models have demonstrated the importance of a priming event (e.g. endotoxin administration) and a role for the protein and lipid biological response modifiers (BRMs) that accumulate during routine blood product storage. This paper focuses on how the key ex vivo and in vivo animal models have progressed our understanding of the mechanisms leading to TRALI.
Andragogi: Pendekatan untuk Meningkatkan Pengetahuan Dan Kemahiran Di Kalangan
Operator Inap Desa Malaysia
Authors: Palal Nor Hairul , Hamzah Amran
Published: March 2018

Homestay, as a community-based tourism product of Malaysia has increased in
popularity and demand among domestic and international tourists. Given that most of
these operators comprised of adults who do not possess any background in the tourism
industry, hence various forms of training should be emphasised in order to raise their
quality of skills and hospitality. In line with the above qualitative approach was
adopted to identify the extent to which a particular adult’s education (andragogy) is
capable of increasing him/her knowledge in ensuring the success in the homestay
programme. A study involving 5 homestays in Johor had produced 3 themes that discuss the
needs of knowledge and skills of homestay operators which consisted of adults aged 40
years old and above.
Doris Lessing’s Fiction as Feminist Projections
Authors: Hossain Md. Amir
Published: March 2018

Doris Lessing, an unrivaled novelist in the literary genres around the globe, portrays the fundamental problems of women as well as social system of her times. Lessing searches for new models to communicate the experiences of a blocked woman writer, who spends her early life in Africa, becomes an active and a disappointed communist, who is a politically committed writer, a mother, a wife, or a mistress sometimes a woman. With her very keen and subtle attitude, Lessing wants to present women’s psychological conflicts between marriage and love; motherhood and profession, unfairness of the double standard; alienation of a single career woman; hollowness of marriage in the traditional order and society. Lessing portrays her women in various social problems and with various perspectives of male against female. She tries to awaken women community to protest against the patriarchy through her feminist writings. For this purpose, this research paper would like to examine the psychological conflicts and traumatic experiences of powerful heroines, including- Anna Wulf of The Golden Notebook, Mary Turner of The Grass Is Singing, and Clefts of The Cleft.
Splenic leukocytes define the resolution of inflammation in heart failure
Authors: Halade Ganesh V. , Norris Paul C. , Kain Vasundhara , Serhan Charles N. , Ingle Kevin A.
Published: March 2018

Leukocytes may be the source of inflammation-resolving lipid mediators after myocardial infarction.
Pilot Study of Model-Based Dosage Individualization of Ganciclovir in Neonates and Young Infants with Congenital Cytomegalovirus Infection
Authors: Dong Qian , Leroux Stephanie , Shi Hai-Yan , Xu Hai-Yan , Kou Chen , Khan Muhammad Wasim , Jacqz-Aigrain Evelyne , Zhao Wei
Published: March 2018

Newborns with congenital cytomegalovirus (CMV) infection are at high risk for developing permanent sequelae. Intravenous ganciclovir therapy is frequently used for the treatment of congenital CMV infection. A target area under the concentration-time curve from 0 to 24 h (AUC
0–24
) of 40 to 50 μg · h/ml is recommended. The standard dose has resulted in a large variability in ganciclovir exposure in newborns, indicating the unmet need of dosage individualization for this vulnerable population, but the implementation of this strategy remains challenging in clinical practice. We aim to evaluate the clinical utility of model-based dosage individualization of ganciclovir in newborns using an opportunistic sampling approach. The predictive performance of a published ganciclovir population pharmacokinetic model was evaluated using an independent patient cohort. The individual dose was adjusted based on the target AUC
0–24
to ensure its efficacy. A total of 26 newborns with congenital CMV infection were included in the present study. Only 11 (42.3%) patients achieved the target AUC
0–24
after being given the standard dose. For all the subtherapeutic patients (achieving <80% of the target AUC) (
n
= 5), a model-based dosage adjustment was performed using the Bayesian estimation method combined with the opportunistic sampling strategy. The adjusted doses were increased by 28.6% to 60.0% in these five patients, and all adapted AUC
0–24
values achieved the target (range, 48.6 to 66.1 μg · h/ml). The clinical utility of model-based dosing individualization of ganciclovir was demonstrated in newborns with congenital CMV infection. The population pharmacokinetic model combined with the opportunistic sampling strategy provides a clinically feasible method to adapt the ganciclovir dose in neonatal clinical practice. (This study has been registered at ClinicalTrials.gov under registration no. NCT03113344.)
Interleukin-18 Is Critical for Mucosa-Associated Invariant T Cell Gamma Interferon Responses to Francisella SpeciesIn Vitrobut NotIn Vivo
Authors: Jesteadt Eric , Zhang Irma , Yu Huifeng , Meierovics Anda , Chua Yankelevich Wei-Jen , Cowley Siobhan
Published: March 2018

Mucosa-associated invariant T (MAIT) cells are a subset of innate T cells that express a semi-invariant Vα chain paired with limited Vβ chains. MAIT cells are activated by riboflavin metabolite derivatives presented by the nonpolymorphic major histocompatibility complex class I (MHC-I)-like molecule MR1. The precise mechanisms required to activate MAIT cells are an area of intense interest. Here we used two closely related intracellular pathogens with distinct inflammasome activation phenotypes to probe the role of innate cytokines in MAIT cell activation. Using anin vitroassay containing transgenic murine MAIT cells, we show that macrophages infected withFrancisella novicida, a strong inflammasome activator, released high levels of interleukin-18 (IL-18) and stimulated high levels of MAIT cell gamma interferon (IFN-γ) through a partially MR1-independent pathway. In contrast, macrophages infected withFrancisella tularensislive vaccine strain (LVS), a weak inflammasome activator, generated little IL-18 and stimulated low MAIT cell IFN-γ through an MR1-dependent pathway. By manipulating the quantities of IL-18 in these cultures, we show that the IL-18 concentration is sufficient to influence the magnitude of MAIT cell IFN-γ production. Correspondingly, infected IL-18-deficient macrophages failed to induce substantial MAIT cell IFN-γ. In contrast, we found that MAIT cell IFN-γ production in the lungs of IL-18-deficient mice was not significantly different from that in WT mice duringF. tularensisLVS pulmonary infection. Overall, we demonstrate that while IL-18 is essential for the MAIT cell IFN-γ responsein vitro, it is not essential for MAIT cell IFN-γ production duringin vivoLVS pulmonary infection, suggesting that additional signals can drive MAIT cell IFN-γ productionin vivo.
Caspase-Dependent Suppression of Type I Interferon Signaling Promotes Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication
Authors: Tabtieng Tate , Degterev Alexei , Gaglia Marta M.
Published: March 2018

An important component of lytic infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is the ability of the virus to evade the innate immune response, specifically type I interferon (IFN) responses that are triggered by recognition of viral nucleic acids. Inhibition of type I IFN responses by the virus promotes viral replication. Here, we report that KSHV uses a caspase-dependent mechanism to block type I IFN, in particular IFN-β, responses during lytic infection. Inhibition of caspases during KSHV reactivation resulted in increased TBK1/IKKε-dependent phosphorylation of IRF3 as well as elevated levels of IFN-β transcription and secretion. The increased secretion of IFN-β upon caspase inhibition reduced viral gene expression, viral DNA replication, and virus production. Blocking IFN-β production or signaling restored viral replication. Overall, our results show that caspase-mediated regulation of pathogen sensing machinery is an important mechanism exploited by KSHV to evade innate immune responses.

IMPORTANCE
KSHV is the causative agent of Kaposi's sarcoma (KS), an AIDS-defining tumor that is one of the most common causes of cancer death in sub-Saharan Africa. In this study, we examined the role of a set of cellular proteases, called caspases, in the regulation of immune responses during KSHV infection. We demonstrate that caspases prevent the induction and secretion of the antiviral factor IFN-β during replicative KSHV infection. The reduced IFN-β production allows for high viral gene expression and viral replication. Therefore, caspases are important for maintaining KSHV replication. Overall, our results suggest that KSHV utilizes caspases to evade innate immune responses, and that inhibiting caspases could boost the innate immune response to this pathogen and potentially be a new antiviral strategy.
Reovirus-Induced Apoptosis in the Intestine Limits Establishment of Enteric Infection
Authors: Brown Judy J. , Short Sarah P. , Stencel-Baerenwald Jennifer , Urbanek Kelly , Pruijssers Andrea J. , McAllister Nicole , Ikizler Mine , Taylor Gwen , Aravamudhan Pavithra , Khomandiak Solomiia , Jabri Bana , Williams Christopher S. , Dermody Terence S.
Published: March 2018

Several viruses induce intestinal epithelial cell death during enteric infection. However, it is unclear whether proapoptotic capacity promotes or inhibits replication in this tissue. We infected mice with two reovirus strains that infect the intestine but differ in the capacity to alter immunological tolerance to new food antigen. Infection with reovirus strain T1L, which induces an inflammatory immune response to fed antigen, is prolonged in the intestine, whereas T3D-RV, which does not induce this response, is rapidly cleared from the intestine. Compared with T1L, T3D-RV infection triggered apoptosis of intestinal epithelial cells and subsequent sloughing of dead cells into the intestinal lumen. We conclude that the infection advantage of T1L derives from its capacity to subvert host restriction by epithelial cell apoptosis, providing a possible mechanism by which T1L enhances inflammatory signals during antigen feeding. Using a panel of T1L × T3D-RV reassortant viruses, we identified the viral M1 and M2 gene segments as determinants of reovirus-induced apoptosis in the intestine. Expression of the T1L M1 and M2 genes in a T3D-RV background was sufficient to limit epithelial cell apoptosis and enhance viral infection to levels displayed by T1L. These findings define additional reovirus gene segments required for enteric infection of mice and illuminate the antiviral effect of intestinal epithelial cell apoptosis in limiting enteric viral infection. Viral strain-specific differences in the capacity to infect the intestine may be useful in identifying viruses capable of ameliorating tolerance to fed antigen in autoimmune conditions like celiac disease.

IMPORTANCE
Acute viral infections are thought to be cleared by the host with few lasting consequences. However, there may be much broader and long-lasting effects of viruses on immune homeostasis. Infection with reovirus, a common, nonpathogenic virus, triggers inflammation against innocuous food antigens, implicating this virus in the development of celiac disease, an autoimmune intestinal disorder triggered by exposure to dietary gluten. Using two reovirus strains that differ in the capacity to abrogate oral tolerance, we found that strain-specific differences in the capacity to replicate in the intestine inversely correlate with the capacity to induce apoptotic death of intestinal epithelial cells, providing a host-mediated process to restrict intestinal infection. This work contributes new knowledge about virus-host interactions in the intestine and establishes a foundation for future studies to define mechanisms by which viruses break oral tolerance in celiac disease.
Human Immunoglobulin G Cannot Inhibit Fibrinogen Binding by the Genetically Diverse A Domain of Staphylococcus aureus Fibronectin-Binding Protein A
Authors: den Reijer P. Martijn , Tavakol Mehri , Lemmens-den Toom Nicole , Allouch Dikra , Thomas Sheila , Ganesh Vannakambadi K. , Ko Ya-Ping , Verbrugh Henri A. , van Wamel Willem J. B.
Published: March 2018

Despite the many
in vitro
and murine
in vivo
studies involving FnBPA, the actual presence of this virulence factor during human infection is less well established. Furthermore, it is currently unknown to what extent sequence variation in such a virulence factor affects the human antibody response and the ability of antibodies to interfere with FnBPA function. This study sheds new light on these issues. First, the uniform presence of a patient’s IgG against FnBPA indicates the presence and importance of this virulence factor during
S. aureus
pathogenesis. Second, the absence of an increase in antibody production in most patients following bacteremia indicates the complexity of
S. aureus
-host interactions, possibly involving immune evasion or lack of expression of FnBPA during invasive infection. Finally, we provide new insights into the inability of human antibodies to interfere with FnBPA-fibrinogen binding. These observations should be taken into account during the development of novel vaccination approaches.
Identification of Novel Viruses in
Amblyomma americanum
, Dermacentor variabilis, and Ixodes scapularis Ticks
Authors: Tokarz Rafal , Sameroff Stephen , Tagliafierro Teresa , Jain Komal , Williams Simon H. , Cucura D. Moses , Rochlin Ilia , Monzon Javier , Carpi Giovanna , Tufts Danielle , Diuk-Wasser Maria , Brinkerhoff Jory , Lipkin W. Ian
Published: March 2018

The incidence of tick-borne disease is increasing, driven by rapid geographical expansion of ticks and the discovery of new tick-associated pathogens. The examination of the tick microbiome is essential in order to understand the relationship between microbes and their tick hosts and to facilitate the identification of new tick-borne pathogens. Genomic analyses using unbiased high-throughput sequencing platforms have proven valuable for investigations of tick bacterial diversity, but the examination of tick viromes has historically not been well explored. By performing a comprehensive virome analysis of the three primary tick species associated with human disease in the United States, we gained substantial insight into tick virome diversity and can begin to assess a potential role of these viruses in the tick life cycle.
Abusive head trauma and the triad: a critique on behalf of RCPCH of ‘Traumatic shaking: the role of the triad in medical investigations of suspected traumatic shaking’
Authors: Debelle Geoffrey David , Maguire Sabine , Watts Patrick , Nieto Hernandez Rosa , Kemp Alison Mary
Published: March 2018

The Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU) has recently published what they purported to be a systematic review of the literature on ‘isolated traumatic shaking’ in infants, concluding that ‘there is limited evidence that the so-called triad (encephalopathy, subdural haemorrhage, retinal haemorrhage) and therefore its components can be associated with traumatic shaking’. This flawed report, from a national body, demands a robust response. The conclusions of the original report have the potential to undermine medico-legal practice. We have conducted a critique of the methodology used in the SBU review and have found it to be flawed, to the extent that children’s lives may be put at risk. Thus, we call on this review to be withdrawn or to be subjected to international scrutiny.