bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host Range of the Conjugative Transfer System of IncP-9 Naphthalene-Catabolic Plasmid NAH7 and Characterization of Its
oriT
Region and Relaxase
Authors: Kishida Kouhei , Inoue Kei , Ohtsubo Yoshiyuki , Nagata Yuji , Tsuda Masataka 
Published: October 2016

ABSTRACT

NAH7 and pWW0 from gammaproteobacterial
Pseudomonas putida
strains are IncP-9 conjugative plasmids that carry the genes for degradation of naphthalene and toluene, respectively. Although such genes on these plasmids are well-characterized, experimental investigation of their conjugation systems remains at a primitive level. To clarify these conjugation systems, in this study, we investigated the NAH7-encoded conjugation system by (i) analyzing the origin of its conjugative transfer (
oriT
)-containing region and its relaxase, which specifically nicks within the
oriT
region for initiation of transfer, and (ii) comparing the conjugation systems between NAH7 and pWW0. The NAH7
oriT
(
oriT
N
) region was located within a 430-bp fragment, and the strand-specific nicking (
nic
) site and its upstream sequences that were important for efficient conjugation in the
oriT
N
region were identified. Unlike many other relaxases, the NAH7 relaxase exhibited unique features in its ability to catalyze, in a conjugation-independent manner, the site-specific intramolecular recombination between two copies of the
oriT
N
region, between two copies of the pWW0
oriT
(
oriT
W
) region (which is clearly different from the
oriT
N
region), and between the
oriT
N
and
oriT
W
regions. The pWW0 relaxase, which is also clearly different from the NAH7 relaxase, was strongly suggested to have the ability to conjugatively and efficiently mobilize the
oriT
N
-containing plasmid. Such a plasmid was, in the presence of the NAH7Δ
nic
derivative, conjugatively transferable to alphaproteobacterial and betaproteobacterial strains in which the NAH7 replication machinery is nonfunctional, indicating that the NAH7 conjugation system has a broader host range than its replication system.

IMPORTANCE
Various studies have strongly suggested an important contribution of conjugative transfer of catabolic plasmids to the rapid and wide dissemination of the plasmid-loaded degradation genes to microbial populations. Degradation genes on such plasmids are often loaded on transposons, which can be inserted into the genomes of the recipient bacterial strains where the transferred plasmids cannot replicate. The aim was to advance detailed molecular knowledge of the determinants of host range for plasmids. This aim is expected to be easily and comprehensively achieved using an experimental strategy in which the
oriT
region is connected with a plasmid that has a broad host range of replication. Using such a strategy in this study, we showed that (i) the NAH7
oriT
-relaxase system has unique properties that are significantly different from other well-studied systems and (ii) the host range of the NAH7 conjugation system is broader than previously thought.
Requirements and access needs of patients with chronic disease to their hospital electronic health record: results of a cross-sectional questionnaire survey
Authors: White H , Gillgrass L , Wood A , Peckham D G 
Published: October 2016

ObjectivesTo identify patient's views on the functionality required for personalised access to the secondary care electronic health record (EHR) and their priorities for development.DesignQuantitative analysis of a cross-sectional self-complete survey of patient views on required EHR functionality from a secondary care EHR, including a patient ranking of functionality.SettingSecondary care patients attending a regional cystic fibrosis unit in the north of England.Participants201 adults (106 (52.7%) males), median age 29 years (range 17–58 years), entered and completed the study. Inclusion criteria are as follows: a confirmed diagnosis of cystic fibrosis, aged 16 years and over, at the time of clinical stability.Outcome measuresQuantitative responses within 4 themes; (1) value placed on aspects of the EHR; (2) access requirements to functions of the EHR; (3) views on information sent to the EHR and (4) patient feedback entered into the EHR. A ranked score for 15 functions of the EHR was obtained.ResultsHighest ratings (% reporting item as very important/important) were reported for access to clinical measures (lung function (94%), C reactive protein (84%), sputum microbiology (81%) and blood results (80%)), medication changes (82%) and lists (83%) and sending repeat prescription (83%) and treatment requests (80%), while sending symptom diaries was less so (62%). Email contact with clinicians was the most valuable communication element of the EHR (84% very important/important). Of 15 features of the EHR (1=most desirable to 15=least desirable), patients identified ‘clinical measures’ (2.62 (CI 2.07 to 3.06)), and ‘access to medication lists’ (4.91 (CI 4.47 to 5.44)), as highest priority for development and the ability to comment on errors/omissions (11.0 (CI 10.6 to 11.5)) or experience of care (11.8 (CI 11.4 to 12.2)) as lowest.ConclusionsPatients want extensive personal access to their hospital EHR, placing high importance on the viewing of practical clinical measures and medication management. These influence routine day-to-day care and are priorities for development.
Focused ultrasound examination of the chest on patients admitted with acute signs of respiratory problems: a study protocol for a pragmatic randomised controlled multicentre trial
Authors: Riishede M , Laursen C B , Teglbjærg L S , Lassen A T , Baatrup G 
Published: October 2016

IntroductionPatients with acute respiratory problems poses a diagnostic challenge because similar symptoms can be caused by various pathological conditions. Focused ultrasound examination (f-US) of the heart and lungs has proven to increase the diagnostic accuracy in these patients. In this protocol of a randomised multicentre trial, we study the effect of f-US of the heart and lungs in patients with respiratory problems performed by emergency physicians (EP) as soon as the patient arrives to the emergency department (ED). The primary outcome is the number of patients with a correct presumptive diagnosis at 4 hours from admission.Methods and analysisThis is a semiblinded randomised prospective study. 288 patients will be included and randomised into the control or intervention group. All patients receive a standard diagnostic evaluation by the EP to assess the primary presumptive diagnosis. Investigators are EP, with varying degrees of experience in f-US, who perform an f-US of the heart and lungs in patients in both treatment arms. f-US results in the intervention group are non-blinded to the treating EP to be included in the assessment of the 4-hour presumptive diagnosis. As standard for correct diagnosis, we perform a blinded journal audit after discharge. As primary analysis, we use the intention-to-treat analysis.ConclusionsThis study is the first multicentre trial in EDs to investigate whether f-US, in the hands of the EP, increases the proportion of correct diagnosis at 4 hours after arrival when performed on patients with respiratory problems.Ethics and disseminationThis trial is conducted in accordance with the Helsinki II Declaration and approved by the Danish Data Protection Agency and the Committee on Biomedical Research Ethics for the Region of Southern Denmark. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal regardless of the outcome.Trial registration numberNCT02550184; Pre-results.
New transfer of care initiative of electronic referral from hospital to community pharmacy in England: a formative service evaluation
Authors: Nazar Hamde , Brice Steven , Akhter Nasima , Kasim Adetayo , Gunning Ann , Slight Sarah P , Watson Neil W 
Published: October 2016

ObjectivesTo evaluate an electronic patient referral system from one UK hospital Trust to community pharmacies across the North East of England.SettingTwo hospital sites in Newcastle-upon-Tyne and 207 community pharmacies.ParticipantsInpatients who were considered to benefit from on-going support and continuity of care after leaving hospital.InterventionElectronic transmission of an information related to patient's medicines to their nominated community pharmacy. Community pharmacists to provide a follow-up consultation tailored to the individual patient needs.Primary and secondary outcomesNumber of referrals made to and received by different types of pharmacies; reasons for referrals; accepted/completed and rejected referred rates; reasons for rejections by community pharmacists; time to action referrals; details of the follow-up consultations; readmission rates at 30, 60 and 90 days post referral and number of hospital bed days.Results2029 inpatients were referred over a 13-month period (1 July 2014–31 July 2015). Only 31% (n=619) of these patients participated in a follow-up consultation; 47% (n=955) of referrals were rejected by community pharmacies with the most common reason being ‘patient was uncontactable’ (35%, n=138). Most referrals were accepted/completed within 7 days of receipt and most rejections were made >2 weeks after referral receipt. Most referred patients were over 60 years of age and referred for a Medicines Use Review (MUR) or enrolment for the New Medicines Service (NMS). Those patients who received a community pharmacist follow-up consultation had statistically significant lower rates of readmissions and shorter hospital stays than those patients without a follow-up consultation.ConclusionsHospital pharmacy staff were able to use an information technology (IT) platform to improve the coordination of care for patients transitioning back home from hospital. Community pharmacists were able to contact the majority of patients and results indicate that patients receiving a follow-up consultation may have lower rates of readmission and shorter hospital stays.
Respiratory health screening for opiate misusers in a specialist community clinic: a mixed-methods pilot study, with integrated staff and service user feedback
Authors: Mitchell Caroline Anne , Pitt Alice , Hulin Joe , Lawson Rod , Ashby Fleur , Appelqvist Ivan , Delaney Brigitte 
Published: October 2016

ObjectivesIncreased rates of illicit drug inhalation are thought to expose opiate misusers (OMUs) to an enhanced risk of respiratory health problems. This pilot study aimed to determine the feasibility of undertaking respiratory screening of OMUs in a community clinic.SettingSingle-centre UK community substance misuse clinic.ParticipantsAll clinic attendees receiving treatment for opiate misuse were eligible to participate. 36 participants (mean age=37) were recruited over a 5-week period. The sample included 26 males and 10 females.Outcome measuresSpirometry without bronchodilation; health related quality of life EQ-5D-3L; Asthma Control Test; Mini Asthma Quality of Life; Clinical COPD Questionnaire and the Treatment Outcome Profile were used to assess the respiratory health of participants. Findings were discussed with staff and service users in 2 patient and public involvement events and feedback was analysed thematically.Results34 participants reported that they had smoked heroin. 8 participants diagnosed with asthma, scored under 13 on the Asthma Control Test, suggesting poorly controlled asthma. Participants (n=28), without a diagnosis of asthma completed the Lung Function Questionnaire. Of these, 79% produced scores under 18, indicating symptoms associated with the development of chronic obstructive pulmonary disease. Spirometry showed 14% of all participants had forced expiratory volume in 1 s/forced vital capacity <0.7 (without bronchodilator), indicating potential obstructive lung disease. Feedback from service users and staff suggested a willingness and capacity to deliver respiratory health screening programmes. Insight towards the difficulties service users have in accessing services and the burden of respiratory health was also provided.ConclusionsIt is feasible to undertake respiratory health screening of OMUs in a community clinic. Larger screening studies are warranted to determine the prevalence of respiratory health problems in this population. Research regarding asthma medicines adherence and access to healthcare among OMUs is also required.
Conceptual model for early health technology assessment of current and novel heart valve interventions
Authors: Huygens Simone A , Rutten-van Mölken Maureen P M H , Bekkers Jos A , Bogers Ad J J C , Bouten Carlijn V C , Chamuleau Steven A J , de Jaegere Peter P T , Kappetein Arie Pieter , Kluin Jolanda , van Mieghem Nicolas M D A , Versteegh Michel I M , Witsenburg Maarten , Takkenberg Johanna J M 
Published: October 2016

ObjectiveThe future promises many technological advances in the field of heart valve interventions, like tissue-engineered heart valves (TEHV). Prior to introduction in clinical practice, it is essential to perform early health technology assessment. We aim to develop a conceptual model (CM) that can be used to investigate the performance and costs requirements for TEHV to become cost-effective.MethodsAfter scoping the decision problem, a workgroup developed the draft CM based on clinical guidelines. This model was compared with existing models for cost-effectiveness of heart valve interventions, identified by systematic literature search. Next, it was discussed with a Delphi panel of cardiothoracic surgeons, cardiologists and a biomedical scientist (n=10).ResultsThe CM starts with the valve implantation. If patients survive the intervention, they can remain alive without complications, die from non-valve-related causes or experience a valve-related event. The events are separated in early and late events. After surviving an event, patients can experience another event or die due to non-valve-related causes. Predictors will include age, gender, NYHA class, left ventricular function and diabetes. Costs and quality adjusted life years are to be attached to health conditions to estimate long-term costs and health outcomes.ConclusionsWe developed a CM that will serve as foundation of a decision-analytic model that can estimate the potential cost-effectiveness of TEHV in early development stages. This supports developers in deciding about further development of TEHV and identifies promising interventions that may result in faster take-up in clinical practice by clinicians and reimbursement by payers.
3D T1-weighted black blood sequence at 3.0 Tesla for the diagnosis of cervical artery dissection
Authors: Luo Yun , Guo Zhen-Ni , Niu Peng-Peng , Liu Yang , Zhou Hong-Wei , Jin Hang , Yang Yi 
Published: October 2016

ObjectiveWe aimed to investigate the value of three-dimensional (3D) T1 volumetric isotropic turbo spin echo acquisition (VISTA) in the diagnosis of cervical artery dissection (CAD).MethodsWe prospectively included patients who were suspected as having a CAD within 1 month of onset. For T1 VISTA, the diagnosis of the dissection was based on the presence of intramural high-signal, intimal flap, double lumen and aneurysmal dilation. The final diagnosis of dissection was based on the clinical history, physical examination, and all of the imaging tests.ResultsA total of 46 patients were included in this study. The final diagnosis of CAD was made for 21 patients. Diagnosis of dissection was made for 20 of the 21 patients after assessing T1 VISTA. A definitive diagnosis of dissection was not made for 5 patients (including 3 patients with digital subtraction angiography) before the T1 VISTA examination. The sensitivity and specificity for T1 VISTA were 95.2% (95% CI, 76.2% to 99.9%) and 100% (95% CI, 86.3% to 100%), respectively. The agreement between the two researchers for T1 VISTA for diagnosis of CAD was very good (k=0.91). For patients without acute artery occlusion, all of them had a definite conclusion with or without dissection by T1 VISTA (n=29). However, for 17 patients with acute artery occlusion, the possibility of dissection could not be excluded for 6 of them by T1 VISTA (p=0.001).Conclusions3D T1 VISTA at 3.0 Tesla was useful in the diagnosis of acute CAD. However, for some patients with total occlusion of the artery without typical imaging features of dissection, the unequivocal distinction between intramural haematoma and intraluminal thrombus may be not adequate by T1 VISTA alone. Future studies should investigate whether a follow-up scan, a contrast-enhanced imaging or an optimal VISTA technique could be useful.
Ubiquitous Release of Exosomal Tumor Suppressor miR-6126 from Ovarian Cancer Cells
Authors: Kanlikilicer Pinar , Rashed Mohammed H. , Bayraktar Recep , Mitra Rahul , Ivan Cristina , Aslan Burcu , Zhang Xinna , Filant Justyna , Silva Andreia M. , Rodriguez-Aguayo Cristian , Bayraktar Emine , Pichler Martin , Ozpolat Bulent , Calin George A. , Sood Anil K. , Lopez-Berestein Gabriel 
Published: October 2016

Abstract
Cancer cells actively promote their tumorigenic behavior by reprogramming gene expression. Loading intraluminal vesicles with specific miRNAs and releasing them into the tumor microenvironment as exosomes is one mechanism of reprogramming whose regulation remains to be elucidated. Here, we report that miR-6126 is ubiquitously released in high abundance from both chemosensitive and chemoresistant ovarian cancer cells via exosomes. Overexpression of miR-6126 was confirmed in healthy ovarian tissue compared with ovarian cancer patient samples and correlated with better overall survival in patients with high-grade serous ovarian cancer. miR-6126 acted as a tumor suppressor by directly targeting integrin-β1, a key regulator of cancer cell metastasis. miR-6126 mimic treatment of cancer cells resulted in increased miR-6126 and decreased integrin-β1 mRNA levels in the exosome. Functional analysis showed that treatment of endothelial cells with miR-6126 mimic significantly reduced tube formation as well as invasion and migration capacities of ovarian cancer cells in vitro. Administration of miR-6126 mimic in an orthotopic mouse model of ovarian cancer elicited a relative reduction in tumor growth, proliferating cells, and microvessel density. miR-6126 inhibition promoted oncogenic behavior by leading ovarian cancer cells to release more exosomes. Our findings provide new insights into the role of exosomal miRNA-mediated tumor progression and suggest a new therapeutic approach to disrupt oncogenic phenotypes in tumors. Cancer Res; 76(24); 7194–207. ©2016 AACR.
Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors
Authors: Ireland Lucy , Santos Almudena , Ahmed Muhammad S. , Rainer Carolyn , Nielsen Sebastian R. , Quaranta Valeria , Weyer-Czernilofsky Ulrike , Engle Danielle D. , Perez-Mancera Pedro A. , Coupland Sarah E. , Taktak Azzam , Bogenrieder Thomas , Tuveson David A. , Campbell Fiona , Schmid Michael C. , Mielgo Ainhoa 
Published: October 2016

Abstract
Tumor-associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors (IGF) 1 and 2, which activate insulin/IGF receptors on pancreatic cancer cells. Immunohistochemical analysis of biopsies from patients with pancreatic cancer revealed that 72% of the patients expressed activated insulin/IGF receptors on tumor cells, and this positively correlates with increased CD163+ TAM infiltration. In vivo, we found that TAM and myofibroblasts were the main sources of IGF production, and pharmacologic blockade of IGF sensitized pancreatic tumors to gemcitabine. These findings suggest that inhibition of IGF in combination with chemotherapy could benefit patients with PDAC, and that insulin/IGF1R activation may be used as a biomarker to identify patients for such therapeutic intervention. Cancer Res; 76(23); 6851–63. ©2016 AACR.
Effects of Exercise on Insulin, IGF Axis, Adipocytokines, and Inflammatory Markers in Breast Cancer Survivors: A Systematic Review and Meta-analysis
Authors: Kang Dong-Woo , Lee Junga , Suh Sang-Hoon , Ligibel Jennifer , Courneya Kerry S. , Jeon Justin Y. 
Published: October 2016

AbstractBackground: Insulin, IGF axis, adiponectin, and inflammatory markers are associated with breast cancer. Given that physical activity improves prognosis of breast cancer survivors, we investigated the effects of exercise on these markers as potential mediators between physical activity and breast cancer.Methods: PubMed, EMBASE, CENTRAL, CINAHL, and SportDiscus were searched up to December 3, 2015, to identify randomized controlled trials (RCT) that investigated the effect of exercise on insulin, IGF axis, and cytokines in breast cancer survivors. Weighted mean difference (WMD) was calculated using either fixed- or random-effects models on the basis of the heterogeneity of the studies.Results: A total of 18 studies involving 681 breast cancer survivors were included, and these numbers were reduced for individual biomarker analyses. We found that exercise significantly reduced fasting insulin levels [WMD, −3.46 μU/mL; 95% confidence interval (CI), −5.97 to −0.95; P = 0.007]. Furthermore, potentially meaningful but statistically nonsignificant changes were observed in insulin resistance (WMD, −0.73; 95% CI, −0.54 to 0.13; P = 0.23), adiponectin (WMD, 1.17 μg/mL; 95% CI, −0.87 to 3.20; P = 0.26), and C-reactive protein (WMD, −1.10 mg/L; 95% CI, −2.39 to 0.20; P = 0.10). Subgroup analyses showed that fasting insulin levels were significantly more impacted in studies in which intervention participants experienced a weight reduction (WMD, −7.10 μU/mL; 95% CI, −10.31 to −3.90; P &lt; 0.001).Conclusions: Exercise reduces fasting insulin levels in breast cancer survivors. This may be due to exercise-induced reductions in body weight.Impact: Practitioners and clinicians may better help breast cancer prognosis be improved through exercise, anticipating physiological effects on cancer. Cancer Epidemiol Biomarkers Prev; 26(3); 355–65. ©2016 AACR.
The Accentual Phrase in Singapore English
Authors: Chong Adam J. , Sneed German James 
Published: October 2016

Abstract
This paper reports on a speech production experiment that explores whether the accentual phrase (AP) represents an abstract level of prosodic phrasing in Singapore English. Specifically, it tests whether the right edge of the AP is associated with phrase-final lengthening, the degree of which can be distinguished from lengthening associated with the intonational phrase (IP). Target words were produced in matched sentence contexts in 3 phrasal positions: AP-medial (wordfinal), AP-final, and IP-final. As predicted, target words in AP-final position were longer than those in AP-medial position and shorter than those in IP-final position. Analysis of target duration and f0 together shows that AP boundaries are well discriminated from medial positions. Together, these results strongly support an AP level of phrasing for Singapore English and highlight its role in predicting timing variability.