bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ixodes persulcatus Ticks as Vectors for the Babesia microti U.S. Lineage in Japan
Authors: Zamoto-Niikura Aya , Morikawa Shigeru , Hanaki Ken-Ichi , Holman Patricia J. , Ishihara Chiaki 
Published: September 2016

ABSTRACTThe U.S. lineage, one of the major clades in theBabesia microtigroup, is known as a causal agent of human babesiosis mostly in the northeastern and upper midwestern United States. This lineage, however, also is distributed throughout the temperate zone of Eurasia with several reported human cases, although convincing evidence of the identity of the specific vector(s) in this area is lacking. Here, the goal was to demonstrate the presence of infectious parasites directly in salivary glands ofIxodes persulcatus, from which U.S. lineage genetic sequences have been detected in Asia, and to molecularly characterize the isolates. Five PCR-positive specimens were individually inoculated into hamsters, resulting in infections in four; consequently, four strains were newly established. Molecular characterization, including 18S rRNA, β-tubulin, andCCT7gene sequences, as well as Western blot analysis and indirect fluorescent antibody assay, revealed that all four strains were identical to each other and to the U.S. lineage strains isolated from rodents captured in Japan. The 18S rRNA gene sequence from the isolates was identical to those fromI. persulcatusin Russia and China, but the genetic and antigenic profiles of the Japanese parasites differ from those in the United States and Europe. Together with previous epidemiological and transmission studies, we conclude thatI. persulcatusis likely the principal vector for theB. microtiU.S. lineage in Japan and presumably in northeastern Eurasia.IMPORTANCEThe major cause of human babesiosis, the tick-borne blood parasiteBabesia microti, U.S. lineage, is widely distributed in the temperate Northern Hemisphere. However, the specific tick vector(s) remains unidentified in Eurasia, where there are people with antibodies to theB. microtiU.S. lineage and cases of human babesiosis. In this study, the first isolation ofB. microtiU.S. lineage fromIxodes persulcatusticks, a principal vector for many tick-borne diseases, is described in Japan. Limited antigenic cross-reaction was found between the Japan and United States isolates. Thus, current serological tests based on U.S. isolates may underestimateB. microtioccurrence outside the United States. This study and previous studies indicate thatI. persulcatusis part of theB. microtiU.S. lineage life cycle in Japan and, presumably, northeastern Eurasia. This report will be important for public health, especially since infection may occur through transfusion, and also to researchers in the field of parasitology.
Long-term effects of adenotonsillectomy in children with obstructive sleep apnoea: protocol for a systematic review
Authors: Damiani Felipe , Rada Gabriel , Gana Juan Cristóbal , Brockmann Pablo E , Alberti Gigliola 
Published: September 2016

IntroductionAdenotonsillar hypertrophy is the most important anatomical factor associated with obstructive sleep apnoea syndrome in children. The American Academy of Pediatrics recommends adenotonsillectomy as the first line of treatment. AT can reduce the apnoea hypopnoea index; however, its effect on long-term outcomes remains unclear.Methods and analysisWe will conduct an electronic search for randomised controlled trials in MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE. We will also identify literature by reviewing the references included in the selected studies and relevant reviews, screening through important scientific conferences, and searching for ongoing trials in the WHO International Clinical Trials Registry Platform. Two researchers will independently undertake selection of studies, data extraction and assessment of the risk of bias of included studies. We will estimate pooled risk ratios for dichotomous data, and mean difference or standardised mean difference for continuous outcomes. A random-effects model will be used for meta-analyses. Data synthesis and other analyses will be conducted using RevMan V.5.3 software.Ethics and disseminationNo ethics approval is considered necessary. The results of this study will be disseminated via peer-reviewed publications and social networks.Trial registration numberCRD42015022102.
Influence of habitual dietary fibre intake on the responsiveness of the gut microbiota to a prebiotic: protocol for a randomised, double-blind, placebo-controlled, cross-over, single-centre study
Authors: Lunken Genelle , Brough Louise , Butts Chrissie , Murphy Rinki , Whelan Kevin , Coad Jane 
Published: September 2016

IntroductionThe commensal gut microbiota have been shown to have an impact on human health as aberrant gut microbiota have been linked to disease. Dietary constituents are influential in shaping the gut microbiota. Diet-specific therapeutic strategies may therefore play a role in optimising human health via beneficial manipulation of the gut microbiota. Research has suggested that an individual's baseline gut microbiota composition may influence how the gut microbiota respond to a dietary intervention and individuals with differing habitual dietary intakes appear to have distinct baseline gut microbiota compositions. The responsiveness of the gut microbiota may therefore be influenced by habitual dietary intakes. This study aims to investigate what influence differing habitual dietary fibre intakes have on the responsiveness of the gut microbiota to a prebiotic intervention.Methods and analysisIn this randomised, double-blind, placebo-controlled, cross-over, single-centre study, 20 low dietary fibre (dietary fibre intake <18 g/day for females and <22 g/day for males) and 20 high dietary fibre (dietary fibre intake ≥25 g/day for females and ≥30 g/day for males) consumers will be recruited. Participants will be randomised to a placebo (Glucidex 29 Premium) or a prebiotic (Synergy 1) intervention for 3 weeks with a 3-week washout followed by 3 weeks of the alternative intervention. Outcome measures of gut microbiota composition (using 16S rRNA gene sequencing) and functional capacity (faecal short chain fatty acid concentrations and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt)) as well as appetite (visual analogue scale appetite questionnaire) will be assessed at the beginning and end of each intervention phase.Ethics and disseminationThe Massey University Human Ethics Committee approved this study (Massey University HEC: Southern A application—15/34). Results will be disseminated through peer-review journal publications, conference presentations and a summary of findings will be distributed to participants.Trial registration numberACTRN12615000922572; Pre-results.
Association between progression-free survival and health-related quality of life in oncology: a systematic review protocol
Authors: Kovic Bruno , Guyatt Gordon , Brundage Michael , Thabane Lehana , Bhatnagar Neera , Xie Feng 
Published: September 2016

IntroductionThere is an increasing number of new oncology drugs being studied, approved and put into clinical practice based on improvement in progression-free survival, when no overall survival benefits exist. In oncology, the association between progression-free survival and health-related quality of life is currently unknown, despite its importance for patients with cancer, and the unverified assumption that longer progression-free survival indicates improved health-related quality of life. Thus far, only 1 study has investigated this association, providing insufficient evidence and inconclusive results. The objective of this study protocol is to provide increased transparency in supporting a systematic summary of the evidence bearing on this association in oncology.Methods and analysisUsing the OVID platform in MEDLINE, Embase and Cochrane databases, we will conduct a systematic review of randomised controlled human trials addressing oncology issues published starting in 2000. A team of reviewers will, in pairs, independently screen and abstract data using standardised, pilot-tested forms. We will employ numerical integration to calculate mean incremental area under the curve between treatment groups in studies for health-related quality of life, along with total related error estimates, and a 95% CI around incremental area. To describe the progression-free survival to health-related quality of life association, we will construct a scatterplot for incremental health-related quality of life versus incremental progression-free survival. To estimate the association, we will use a weighted simple regression approach, comparing mean incremental health-related quality of life with either median incremental progression-free survival time or the progression-free survival HR, in the absence of overall survival benefit.DiscussionIdentifying direction and magnitude of association between progression-free survival and health-related quality of life is critically important in interpreting results of oncology trials. Systematic evidence produced from our study will contribute to improvement of patient care and practice of evidence-based medicine in oncology.
Discrepancies between patient-reported outcomes, and endoscopic and histological appearance in UC
Authors: Colombel Jean-Frédéric , Keir Mary E , Scherl Alexis , Zhao Rui , de Hertogh Gert , Faubion William A , Lu Timothy T 
Published: September 2016

ObjectiveBoth endoscopy and histology may be included in the definition of mucosal healing in UC. This study aimed to establish the association between patient-reported outcomes, specifically symptom measures, and the presence of inflammation as measured by endoscopy and histology in UC.DesignUsing patient data from an observational multicentre study of UC (n=103), rectal bleeding (RB) and stool frequency (SF) symptom subscores of the Mayo Clinic Score (MCS) were compared with the endoscopic subscore (MCSe) and histology. Faecal calprotectin and biopsy cytokine expression were also evaluated.ResultsWhen identifying UC patients with inactive disease, RB scores were superior to SF scores and the combination (sensitivity/specificity: MCSe=0/1, RB 77%/81%, SF 62%/95%, RB+SF 54%/95%; MCSe=0, RB 87%/66%, SF 76%/83%, RB+SF 68%/86%). Across different definitions of mucosal healing (MCSe≤1; 0; or 0 plus inactive histology), a larger subset of patients reported increased SF (39%, 25% and 27%, respectively) compared with RB (24%, 13% and 10%). Faecal calprotectin and inflammatory cytokine expression were higher in patients with active disease compared with patients with mucosal healing, but there were no differences between patients using increasingly stringent definitions of mucosal healing.ConclusionsEndoscopically inactive disease is associated with absence of RB but not with complete normalisation of SF. Achieving histological remission did not improve symptomatic relief. In addition, in these patients, higher inflammatory biomarker levels were not observed. These data suggest that non-inflammatory changes, such as bowel damage, may contribute to SF in UC.
TNF receptor signaling inhibits cardiomyogenic differentiation of cardiac stem cells and promotes a neuroadrenergic-like fate
Authors: Hamid Tariq , Xu Yuanyuan , Ismahil Mohamed Ameen , Li Qianhong , Jones Steven P. , Bhatnagar Aruni , Bolli Roberto , Prabhu Sumanth D. 
Published: September 2016

Despite expansion of resident cardiac stem cells (CSCs; c-kit+Lin−) after myocardial infarction, endogenous repair processes are insufficient to prevent adverse cardiac remodeling and heart failure (HF). This suggests that the microenvironment in post-ischemic and failing hearts compromises CSC regenerative potential. Inflammatory cytokines, such as tumor necrosis factor-α (TNF), are increased after infarction and in HF; whether they modulate CSC function is unknown. As the effects of TNF are specific to its two receptors (TNFRs), we tested the hypothesis that TNF differentially modulates CSC function in a TNFR-specific manner. CSCs were isolated from wild-type (WT), TNFR1−/−, and TNFR2−/− adult mouse hearts, expanded and evaluated for cell competence and differentiation in vitro in the absence and presence of TNF. Our results indicate that TNF signaling in murine CSCs is constitutively related primarily to TNFR1, with TNFR2 inducible after stress. TNFR1 signaling modestly diminished CSC proliferation, but, along with TNFR2, augmented CSC resistance to oxidant stress. Deficiency of either TNFR1 or TNFR2 did not impact CSC telomerase activity. Importantly, TNF, primarily via TNFR1, inhibited cardiomyogenic commitment during CSC differentiation, and instead promoted smooth muscle and endothelial fates. Moreover, TNF, via both TNFR1 and TNFR2, channeled an alternate CSC neuroadrenergic-like fate (capable of catecholamine synthesis) during differentiation. Our results suggest that elevated TNF in the heart restrains cardiomyocyte differentiation of resident CSCs and may enhance adrenergic activation, both effects that would reduce the effectiveness of endogenous cardiac repair and the response to exogenous stem cell therapy, while promoting adverse cardiac remodeling.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/tnf-and-cardiac-stem-cell-differentiation/ .
Ovarian Cancer Chemoresistance Relies on the Stem Cell Reprogramming Factor PBX1
Authors: Jung Jin-Gyoung , Shih Ie-Ming , Park Joon Tae , Gerry Emily , Kim Tae Hoen , Ayhan Ayse , Handschuh Karen , Davidson Ben , Fader Amanda N. , Selleri Licia , Wang Tian-Li 
Published: September 2016

Abstract
The evolution of chemoresistance is a fundamental characteristic of cancer that ultimately hampers its clinical management. However, it may be possible to improve patient outcomes significantly by a better understanding of resistance mechanisms, which cancers rely upon during the evolution to an untreatable state. Here we report an essential role of the stem cell reprogramming factor, PBX1, in mediating chemoresistance in ovarian carcinomas. In the clinical setting, high levels of PBX1 expression correlated with shorter survival in post-chemotherapy ovarian cancer patients. In tumor cells with low endogenous levels of PBX1, its enforced expression promoted cancer stem cell-like phenotypes, including most notably an increase in resistance to platinum-based therapy used most commonly for treating this disease. Conversely, silencing PBX1 in platinum-resistant cells that overexpressed PBX1 sensitized them to platinum treatment and reduced their stem-like properties. An analysis of published genome-wide chromatin immunoprecipitation data indicated that PBX1 binds directly to promoters of genes involved in stem cell maintenance and the response to tissue injury. We confirmed direct regulation of one of these genes, STAT3, demonstrating that the PBX1 binding motif at its promoter acted to positively regulate STAT3 transcription. We further demonstrated that a STAT3/JAK2 inhibitor could potently sensitize platinum-resistant cells to carboplatin and suppress their growth in vivo. Our findings offer a mechanistic rationale to target the PBX1/STAT3 axis to antagonize a key mechanism of chemoresistance in ovarian cancers and possibly other human cancers. Cancer Res; 76(21); 6351–61. ©2016 AACR.
Neddylation E2 UBE2F Promotes the Survival of Lung Cancer Cells by Activating CRL5 to Degrade NOXA via the K11 Linkage
Authors: Zhou Weihua , Xu Jie , Li Haomin , Xu Ming , Chen Zhijian J. , Wei Wenyi , Pan Zhenqiang , Sun Yi 
Published: September 2016

Abstract
Purpose: Recent studies have shown that the process of protein neddylation was abnormally activated in several human cancers. However, it is unknown whether and how UBE2F, a less characterized neddylation E2, regulates lung cancer cell survival, and whether and how NOXA, a proapoptotic protein, is ubiquitylated and degraded by which E3 and via which ubiquitin linkage.
Experimental Design: Methods of immunohistochemistry and immunoblotting were utilized to examine UBE2F protein expression. The biological functions of UBE2F were evaluated by in vitro cell culture and in vivo xenograft models. The in vivo complex formation among UBE2F-SAG-CUL5-NOXA was measured by a pulldown assay. Polyubiquitylation of NOXA was evaluated by in vivo and in vitro ubiquitylation assays.
Results: UBE2F is overexpressed in non–small cell lung cancer (NSCLC) and predicts poor patient survival. While UBE2F overexpression promotes lung cancer growth both in vitro and in vivo, UBE2F knockdown selectively inhibits tumor growth. By promoting CUL5 neddylation, UBE2F/SAG/CUL5 tri-complex activates CRL5 (Cullin-RING-ligase-5) to ubiquitylate NOXA via a novel K11, but not K48, linkage for targeted proteasomal degradation. CRL5 inactivation or forced expression of K11R ubiquitin mutant caused NOXA accumulation to induce apoptosis, which is rescued by NOXA knockdown. Notably, NOXA knockdown rescues the UBE2F silencing effect, indicating a causal role of NOXA in this process. In lung cancer tissues, high levels of UBE2F and CUL5 correlate with a low level of NOXA and poor patient survival.
Conclusions: By ubiquitylating and degrading NOXA through activating CRL5, UBE2F selectively promotes lung cancer cell survival and could, therefore, serve as a novel cancer target. Clin Cancer Res; 23(4); 1104–16. ©2016 AACR.
HPI reactivity does not reflect changes in personality among trout introduced to bold or shy social groups
Authors: Thomson Jack S. , Watts Phillip C. , Pottinger Tom G. , Sneddon Lynne U. 
Published: September 2016

Physiological stress responses often correlate with personalities (e.g., boldness). However, this relationship can become decoupled, although the mechanisms underlying changes in this relationship are poorly understood. Here we quantify (1) how an individual’s boldness (response to novel objects) in rainbow trout,Oncorhynchus mykiss, changes in response to interactions with a population of either bold or shy conspecifics and we (2) measured associated post-stress cortisol levels. Initially-bold trout became shyer regardless of group composition, whereas shy trout remained shy demonstrating that bold individuals are more plastic. Stress-induced plasma cortisol reflected the original personality of fish but not the personality induced by the treatment, irrespective of population personality. Change in boldness of bold trout may indicate preference towards initially subordinate behaviour when joining a new population. However, here we provide further evidence that behavioural and physiological parameters of coping styles may become uncoupled whereby behavioural changes are not correlated with stress responsiveness.
Children’s after-school physical activity participation in Hong Kong: Does family socioeconomic status matter?
Authors: Cheung Peggy PY 
Published: September 2016

Objective: This study aimed to examine the association between parental socioeconomic status (SES) and children’s physical activity (PA) behaviour during after-school hours. Design: Cross-sectional study. Methods: Participants included 663 schoolchildren (aged between 10 and 13 years) and their parents from nine primary schools in Hong Kong. Parental SES status and the after-school PA levels of children were assessed using self-administered questionnaires. Analysis of variance (ANOVA) was conducted to examine the association between parents’ education and income level and the type of activities in which children participated during after-school hours. Results: Results indicated that children with mother in the higher education group engaged in fewer time blocks of sports-type activity (high = 0.72 time blocks; medium = 1.04 time blocks; low = 1.17 time blocks). Compared with their counterparts, children with mothers in the higher income group were more engaged in sedentary activity (high = 5.33 time blocks; medium = 5.02 time blocks; low = 4.73 time blocks) within the eight 30-minute time blocks during after-school hours. Conclusion: The study describes how parental SES influences children’s after-school PA participation and highlights the importance of including a family perspective when designing a PA promotion programme targeting after-school hours.
SMS for sexual health: A comparison of service types and recommendations for sexual health text message service providers
Authors: Willoughby Jessica Fitts , Muldrow Adrienne 
Published: September 2016

Objectives: Text message–based interventions may provide sexual health information to young people through a number of service types, from sending information on a regularly scheduled timeline, to providing an automated menu, to allowing young people to connect directly with health educators. While such service types exist, it is not clear which features young adults feel are most effective at allowing them to engage with sexual health information. Design: This study used a mixed-methods design (survey and focus groups) to assess perceptions of three types of sexual health text message services with young adults, a population particularly at risk of negative sexual health outcomes. Setting: College students from the US Pacific Northwest participated in the project. Method: Participants heard about three sexual health text message services, completed questionnaires and discussed each type. Focus groups were gender-separated. Results: Participants reported that services that allowed them to connect with a health educator would be highly useful, but automated services would be beneficial in bringing new topics to their attention. Participants perceived the purpose of the service types as different and felt each could be a useful resource, depending on the situation. Regardless of service type, participants wanted to personalise their experience. Participants wanted messages tailored to them and options to interact with the systems, from influencing topic selection to message timing. Conclusion: Each of the service types can be useful for young adults. Young adults perceive services that provide the opportunity to tailor information and interact with the system as beneficial.
The Automation-by-Expertise-by-Training Interaction
Authors: Strauch Barry 
Published: September 2016

Objective: I introduce the automation-by-expertise-by-training interaction in automated systems and discuss its influence on operator performance. Background: Transportation accidents that, across a 30-year interval demonstrated identical automation-related operator errors, suggest a need to reexamine traditional views of automation. Method: I review accident investigation reports, regulator studies, and literature on human computer interaction, expertise, and training and discuss how failing to attend to the interaction of automation, expertise level, and training has enabled operators to commit identical automation-related errors. Results: Automated systems continue to provide capabilities exceeding operators’ need for effective system operation and provide interfaces that can hinder, rather than enhance, operator automation-related situation awareness. Because of limitations in time and resources, training programs do not provide operators the expertise needed to effectively operate these automated systems, requiring them to obtain the expertise ad hoc during system operations. As a result, many do not acquire necessary automation-related system expertise. Conclusion: Integrating automation with expected operator expertise levels, and within training programs that provide operators the necessary automation expertise, can reduce opportunities for automation-related operator errors. Application: Research to address the automation-by-expertise-by-training interaction is needed. However, such research must meet challenges inherent to examining realistic sociotechnical system automation features with representative samples of operators, perhaps by using observational and ethnographic research. Research in this domain should improve the integration of design and training and, it is hoped, enhance operator performance.