bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for a randomised controlled trial to study cryoprevention of chemotherapy-induced oral mucositis after autologous stem cell transplantation
Authors: Walladbegi Java , Svanberg Anncarin , Gellerstedt Martin 
Published: October 2018

IntroductionA majority of patients who receive myeloablative therapy prior to hematopoetic stem cell transplantation develop oral mucositis (OM). This adverse cytotoxic effect manifests as oral mucosal erythema and ulcerations and frequently necessitates high doses of morphine for pain alleviation. OM may also interfere with food intake and result in parenteral nutrition, weight loss and impaired quality of life. To date, there have been a few studies of evidence-based interventions for prevention of OM. Cooling the oral mucosa using ice chips in conjunction with chemotherapy is known to reduce the severity of OM although clinical application is still limited due to several disadvantages. The primary endpoint of this study is therefore to evaluate the efficacy of an innovative intraoral cooling device (Cooral) compared with ice cooling in reducing the degree of OM, in patients with myeloma or lymphoma.Method and analysisA total of 180 patients from four different university hospitals in Sweden will be randomised to ice or Cooral in a proportion of 1:1. The degree of OM will be assessed at eight intraoral locations, in accordance with the Oral Mucositis Assessment Scale and WHO scale. Patients will be registered beginning at admission and will continue until discharge or until day +28. The primary variable is analysed in a multiple linear regression model. The significance level used is 5%.Ethics and disseminationThe study protocol, questionnaire, diaries and letter of invitation to participants have been reviewed by the local ethical board in Göteborg. The trial results will be published in a peer-reviewed journal and disseminated to participants.Trial registration numberNCT03203733; Pre-results.Protocol versionVersion 4, 2017-06-05
Caesarean section in Palestine using the Robson Ten Group Classification System: a population-based birth cohort study
Authors: Zimmo Mohammed Walid , Laine Katariina , Hassan Sahar , Bottcher Bettina , Fosse Erik , Ali-Masri Hadil , Zimmo Kaled , Sørum Falk Ragnhild , Lieng Marit , Vikanes Åse 
Published: October 2018

ObjectiveTo analyse the current situation of caesarean section in Palestine using the Robson Ten Group Classification System (TGCS).DesignA population-based birth cohort study.SettingObstetrical departments in three governmental hospitals in Gaza.ParticipantsAll women (18 908) who gave birth between 1 January 2016 and 30 April 2017.MethodsThe contributions of each group to the study population and to the overall rate of caesarean section were calculated, as well as the rate of caesarean section in each TGCS group. Differences in proportions between study hospitals were assessed by χ2 test.Main outcome measuresThe main outcome was the contributions of each group to the overall caesarean section rate.ResultsThe overall rate of caesarean section was 22.9% (4337 of 18 908), ranging from 20.6% in hospital 1 to 24.6% in hospital 3. The largest contributors to the overall caesarean section rate were multiparous women with single cephalic full-term pregnancy who had undergone at least one caesarean section (group 5, 42.6%), women with multiple pregnancies (group 8, 11.6%) and those with single cephalic preterm labour (group 10, 8.1%). Statistically significant differences in caesarean section rates between the study hospitals were observed in group 1 (nulliparous women with single cephalic full-term pregnancy and spontaneous labour), group 4 (multiparous with single cephalic full-term pregnancy with induced labour or prelabour caesarean section), group 5 (multiparous with single cephalic full-term pregnancy with previous caesarean section) and in group 7 (multiparous with breech presentation).ConclusionWomen in groups 5, 8 and 10 were the largest contributors to the overall caesarean section rate in the study hospitals. Efforts to reduce the differences in obstetrical care between hospitals need to be directed towards increasing the proportion of vaginal births after caesarean section and by reducing primary caesarean section in multiple pregnancies and preterm labour.
Qualitative study to explore the views of general practice staff on the use of point-of-care C reactive protein testing for the management of lower respiratory tract infections in routine general practice in England
Authors: Eley Charlotte Victoria , Sharma Anita , Lecky Donna Marie , Lee Hazel , McNulty Cliodna Ann Miriam 
Published: October 2018

ObjectivesTo explore the knowledge, skills, attitudes and beliefs of general practice staff about C reactive protein (CRP) point-of-care tests (POCTs) in routine general practice and associated barriers and facilitators to implementing it to improve the management of acute cough.DesignA qualitative methodology including interviews and focus groups using the Com-B framework to understand individuals’ behaviour to implement CRP POCT in routine general practice. Data were analysed inductively and then aligned to the Com-B framework.SettingA service evaluation of CRP POCT over a 6-month period was previously conducted in randomly selected GP practices from a high prescribing National Health Service Clinicial Commissioning Groups in England. All 11 intervention practices (eight accepting CRPs; three declining CRPs) and the eight control practices, which were not offered CRP POCT, were also invited to interview. A further randomly selected practice not allocated to intervention or control was also invited to participate.ParticipantsSeven of eight accepting CRP, one of three declining CRP and four of nine control practices consented to participate. 12 practices and 26 general practice staff participated; 11 interviews, 3 focus groups and 1 hand-written response.ResultsParticipants reported that CRP POCT can increase diagnostic certainty for acute cough, inform appropriate management, manage patient expectations for antibiotics, support patient education and improve appropriate antibiotic prescribing. Reported barriers to implementing CRP POCT included: CRP cost, time, easy access to the POCT machine and effects on clinical workflow. Participants with greater CRP use usually had a dedicated staff member with the machine located in their consultation room.ConclusionsCRP POCT can help general practice staff improve patient care and education if incorporated into routine care, but this will need enthusiasts with dedicated POCT instruments or smaller, cheaper, more portable machines. In addition, funding will be needed to support test costs and staff time.
Out-of-hospital initiation of hypothermia in ST-segment elevation myocardial infarction: a randomised trial
Authors: Testori Christoph , Beitzke Dietrich , Mangold Andreas , Sterz Fritz , Loewe Christian , Weiser Christoph , Scherz Thomas , Herkner Harald , Lang Irene 
Published: October 2018

ObjectiveTo evaluate the effect of prereperfusion hypothermia initiated in the out-of-hospital setting in awake patients with ST-segment elevation myocardial infarction (STEMI) on myocardial salvage measured by cardiac MRI (CMR).MethodsHypothermia was initiated within 6 hours of symptom onset by the emergency medical service with surface cooling pads and cold saline, and continued in the cath lab with endovascular cooling (target temperature: ≤35°C at time of reperfusion). Myocardial salvage index (using CMR) was compared in a randomised, controlled, open-label, endpoint blinded trial to a not-cooled group of patients at day 4±2 after the event.ResultsAfter postrandomisation exclusion of 19 patients a total of 101 patients were included in the intention-to-treat analysis (control group: n=54; hypothermia group: n=47). Target temperature was reached in 38/47 patients (81%) in the intervention group. Study-related interventions resulted in a delay in time from first medical contact to reperfusion of 14 min (control group 89±24 min; hypothermia group 103±21 min; p<0.01). Myocardial salvage index was 0.37 (±0.26) in the control group and 0.43 (±0.27) in the hypothermia group (p=0.27). No differences in cardiac biomarkers or clinical outcomes were found. In a CMR follow-up 6 months after the initial event no significant differences were detected.ConclusionOut-of-hospital induced therapeutic hypothermia as an adjunct to primary percutaneous coronary intervention did not improve myocardial salvage in patients with STEMI.Trial registration numberNCT01777750
Cadherin-11 as a regulator of valve myofibroblast mechanobiology
Authors: Bowler Meghan A. , Bersi Matthew R. , Ryzhova Larisa M. , Jerrell Rachel J. , Parekh Aron , Merryman W. David 
Published: October 2018

Cadherin-11 (CDH11) is upregulated in a variety of fibrotic diseases, including arthritis and calcific aortic valve disease. Our recent work has identified CDH11 as a potential therapeutic target and shown that treatment with a CDH11 functional blocking antibody can prevent hallmarks of calcific aortic valve disease in mice. The present study investigated the role of CDH11 in regulating the mechanobiological behavior of valvular interstitial cells believed to cause calcification. Aortic valve interstitial cells were harvested from Cdh11+/+, Cdh11+/−, and Cdh11−/− immortomice. Cells were subjected to inflammatory cytokines transforming growth factor (TGF)-β1 and IL-6 to characterize the molecular mechanisms by which CDH11 regulates their mechanobiological changes. Histology was performed on aortic valves from Cdh11+/+, Cdh11+/−, and Cdh11−/− mice to identify key responses to CDH11 deletion in vivo. We showed that CDH11 influences cell behavior through its regulation of contractility and its ability to bind substrates via focal adhesions. We also show that transforming growth factor-β1 overrides the normal relationship between CDH11 and smooth muscle α-actin to exacerbate the myofibroblast disease phenotype. This phenotypic switch is potentiated through the IL-6 signaling axis and could act as a paracrine mechanism of myofibroblast activation in neighboring aortic valve interstitial cells in a positive feedback loop. These data suggest CDH11 is an important mediator of the myofibroblast phenotype and identify several mechanisms by which it modulates cell behavior. NEW & NOTEWORTHY Cadherin-11 influences valvular interstitial cell contractility by regulating focal adhesions and inflammatory cytokine secretion. Transforming growth factor-β1 overrides the normal balance between cadherin-11 and smooth muscle α-actin expression to promote a myofibroblast phenotype. Cadherin-11 is necessary for IL-6 and chitinase-3-like protein 1 secretion, and IL-6 promotes contractility. Targeting cadherin-11 could therapeutically influence valvular interstitial cell phenotypes in a multifaceted manner.
BMI1 promotes cardiac fibrosis in ischemia-induced heart failure via the PTEN-PI3K/Akt-mTOR signaling pathway
Authors: Yang Wenbo , Wu Zhijun , Yang Ke , Han Yanxin , Chen Yanjia , Zhao Weilin , Huang Fanyi , Jin Yao , Jin Wei 
Published: October 2018

Cardiac fibrosis has been known to play an important role in the etiology of heart failure after myocardial infarction (MI). B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a transcriptional repressor, is important for fibrogenesis in the kidneys. However, the effect of BMI1 on ischemia-induced cardiac fibrosis remains unclear. BMI1 was strongly expressed in the infarct region 1 wk post-MI in mice and was detected by Western blot and histological analyses. Lentivirus-mediated overexpression of BMI1 significantly promoted cardiac fibrosis, worsened cardiac function 4 wk after the intervention in vivo, and enhanced the proliferation and migration capabilities of fibroblasts in vitro , whereas downregulation of BMI1 decreased cardiac fibrosis and prevented cardiac dysfunction in mice 4 wk post-MI in vivo. Furthermore, upregulated BMI1 inhibited phosphatase and tensin homolog (PTEN) expression, enhanced phosphatidylinositol 3-kinase (PI3K) expression, and increased the phosphorylation level of Akt and mammalian target of rapamycin (mTOR) in mice 4 wk after lentiviral infection, which was in accordance with the changes seen in their infarcted myocardial tissues. At the same time, the effects of BMI1 on cardiac fibroblasts were reversed in vitro when these cells were exposed to NVP-BEZ235, a dual-kinase (PI3K/mTOR) inhibitor. In conclusion, BMI1 is associated with cardiac fibrosis and dysfunction after MI by regulating cardiac fibroblast proliferation and migration, and these effects could be partially explained by the regulation of the PTEN-PI3K/Akt-mTOR pathway. NEW & NOTEWORTHY Ischemia-induced B lymphoma Mo-MLV insertion region 1 homolog (BMI1) significantly promoted cardiac fibrosis and worsened cardiac function in vivo, whereas downregulation of BMI1 decreased cardiac fibrosis and prevented cardiac dysfunction in myocardial infarcted mice. BMI1 also enhanced proliferation and migration capabilities of fibroblasts in vitro; these effects were reversed by NVP-BEZ235. Effects of BMI1 on cardiac fibrosis could be partially explained by regulation of the phosphatase and tensin homolog-phosphatidylinositol 3-kinase/Akt-mammalian target of rapamycin pathway.
Comparative Pharmacokinetic Study of Mangiferin in Normal and Alloxan-Induced Diabetic Rats after Oral and Intravenous Administration by UPLC-MS/MS
Authors: Gu Peng-Cheng , Wang Lan , Han Mei-Na , Peng Jun , Shang Jing-Chuan , Pan Yong-Quan , Han Wen-Li 
Published: October 2018

<b><i>Backgrounds:</i></b> Diabetes mellitus (DM)-induced morphological and/or functional complications may alter the pharmacokinetic profiles of mangiferin. This study aims to compare pharmacokinetic profiles of mangiferin in normal and alloxan-induced diabetic rats after oral and intravenous administration. <b><i>Methods:</i></b> Mangiferin was administered orally (10 mg/kg) and intravenously (2 mg/kg) to normal and alloxan-induced diabetic Sprague-Dawley (SD) rats (<i>n</i> = 8). Blood samples were collected at different time points post-dose. Mangiferin and esculentoside (internal standard) were analyzed by Waters Acquity ultra-performance liquid chromatography system and TSQ Quantum Ultra triple quadrupole mass spectrometer (UPLC-MS/MS). <b><i>Results:</i></b> Mangiferin in normal and alloxan-induced diabetic rats experienced serious first-pass effect, which resulted in 1.71 and 0.80% of oral bioavailability respectively. Meanwhile, mangiferin was predominantly restricted to blood but not extensively distributed to organ tissues after intravenous administration. Compared with normal rats, the diabetic condition induced 53.26 and 50.90% decreases in C<sub>max</sub> and AUC<sub>0–t</sub>, respectively, for mangiferin after oral administration, and 63.08% decreases in C<sub>max</sub> after intravenous administration. <b><i>Conclusions:</i></b> Compared to normal rats, pharmacokinetic parameters of mangiferin were altered in diabetic condition induced by alloxan. The findings might help to provide useful evidence for modeling of diabetic rats and the clinical applications of mangiferin.
Faster Hypothermia Induced by Esophageal Cooling Improves Early Markers of Cardiac and Neurological Injury After Cardiac Arrest in Swine
Authors: Xu Jiefeng , Jin Xiaohong , Chen Qijiang , Wu Chunshuang , Li Zilong , Zhou Guangju , Xu Yongan , Qian Anyu , Li Yulin , Zhang Mao 
Published: October 2018

Background

After cardiopulmonary resuscitation, the protective effects of therapeutic hypothermia induced by conventional cooling are limited. Recently, esophageal cooling (
EC
) has been shown to be an effective, easily performed approach to induce therapeutic hypothermia. In this study we investigated the efficacy of
EC
and its effects on early markers of postresuscitation cardiac and neurological injury in a porcine model of cardiac arrest.

Methods and Results

Thirty‐two male domestic swine were randomized into 4 groups: sham control, normothermia, surface cooling, and
EC
. Sham animals underwent the surgical preparation only. Ventricular fibrillation was induced and untreated for 8 minutes while defibrillation was attempted after 5 minutes of cardiopulmonary resuscitation. At 5 minutes after resuscitation, therapeutic hypothermia was induced by either
EC
or surface cooling to reach a target temperature of 33°C until 24 hours postresuscitation, followed by a rewarming rate of 1°C/h for 5 hours. The temperature was normally maintained in the control and normothermia groups. After resuscitation, a significantly faster decrease in blood temperature was observed in the
EC
group than in the surface cooling group (2.8±0.7°C/h versus 1.5±0.4°C/h;
P
<0.05). During the maintenance and rewarming phases the temperature was maintained at an even level between the 2 groups. Postresuscitation cardiac and neurological damage was significantly improved in the 2 hypothermic groups compared with the normothermia group; however, the protective effects were significantly greater in the
EC
group.

Conclusions

In a porcine model of cardiac arrest, faster hypothermia successfully induced by
EC
was significantly better than conventional cooling in improving early markers of postresuscitation cardiac and neurological injury.
Individual variation in the dear enemy phenomenon via territorial vocalizations in red squirrels
Authors: Robertson Jack G. , Boutin Stan , Humphries Murray M. , Dantzer Ben , Lane Jeffrey E. , McAdam Andrew G. 
Published: October 2018

Abstract
Territoriality arises when the benefits of resources exceed the costs of defending them. The dear enemy phenomenon, where familiar territorial neighbours refrain from intruding on one another and mutually reduce their defensive efforts, allows for reduction of these costs but requires discrimination between conspecifics. We hypothesized that territorial vocalizations in red squirrels (Tamiasciurus hudsonicus) are used for this discrimination. We performed a speaker replacement experiment where red squirrels () were temporarily removed from their territories and replaced with a speaker broadcasting their own call, an unfamiliar call, or silence. Contrary to our prediction, there were no differences in overall intrusion risk among our three playbacks, but the identity of intruders did vary. Existing variation in familiarity within territorial neighbourhoods should be considered, rather than the binary classification of familiar or stranger, when studying dear enemy effects. We also discuss the variable importance of silence in acoustic territorial populations.
Estimation of lipid reserves in different life stages of Meloidogyne incognita using image analysis of Nile Red-stained nematodes
Authors: Shivakumara Tagginahalli N. , Dutta Tushar K. , Mandal Abhishek , Rao Uma 
Published: October 2018

SummaryBiochemical analyses of nematodes have revealed that neutral lipids (especially triglycerides) are the main source of energy reserves, which is depleted as the nematodes age. Several methodologies have been developed to visualise triglyceride-rich fat stores in plant-parasitic nematodes using non-fluorescent, lipophilic dyes, such as Oil Red O. Here, we propose a robust and reproducible fluorescence-based Nile Red staining method (followed by image analysis) for rapid detection of neutral lipid droplets inMeloidogyne incognita. This unique lipophilic dye selectively fluoresces in red and green spectra in a lipid-rich environment. The neutral lipid content ofM. incognitajuveniles gradually diminished during different periods of food deprivation, and this was significantly correlated with reduction in parasitic success ofM. incognitain eggplant. Additionally, variation in fat reserves in different developmental stages ofM. incognitainfecting adzuki bean was also demonstrated. This investigation may aid future metabolic research, including functional analysis of lipid regulatory genes in plant-parasitic nematodes.
Inter se Modification of the UN Drug Control Conventions
Authors: Boister Neil , Jelsma Martin 
Published: October 2018

Abstract
Legal tensions are growing as more jurisdictions move towards legal regulation of the cannabis market in contravention of the obligation under UN drug control treaties to limit cannabis exclusively to medical and scientific purposes. Reaching a global consensus to amend the conventions does not appear to be a viable political option in the foreseeable future. Amongst the limited options not requiring consensus, inter se modification – based on article 41 of the Vienna Convention on the Law of Treaties – provides a useful safety valve for collective action to adjust a treaty regime arguably frozen in time. Restrictions imposed on inter se modification require a clear commitment to the original treaty aim to promote the health and welfare of humankind and to the original treaty obligations vis-à-vis states not party to the agreement. A coordinated collective response has benefits compared to a chaotic scenario of multiple unilateral reservations and questionable re-interpretations.
Evaluation of the Quasi-Biweekly Oscillation over the South China Sea in Early and Late Summer in CAM5
Authors: Wang Xu , Zhang Guang J. 
Published: October 2018

Abstract
Low-frequency intraseasonal oscillations in the tropical atmosphere in general circulation models (GCMs) were studied extensively in many previous studies. However, the simulation of the quasi-biweekly oscillation (QBWO), which is an important component of the intraseasonal oscillations, in GCMs has not received much attention. This paper evaluates the QBWO features over the South China Sea in early [May–June (MJ)] and late [August–September (AS)] summer in the National Center for Atmospheric Research (NCAR) Community Atmosphere Model, version 5.3 (CAM5), using observations and reanalysis data. Results show that the major features of the spatial distribution of the QBWO in both MJ and AS are simulated reasonably well by the model, although the amplitude of the variation is overestimated. CAM5 captures the local oscillation in MJ and the westward propagation in AS of the QBWO. Although there are important biases in geographical location and intensity in MJ, the model represents the QBWO horizontal and vertical structure qualitatively well in AS. The diagnosis of the eddy vorticity budget is conducted to better understand the QBWO activities in the model. Both horizontal advection of relative vorticity and that of planetary vorticity (Coriolis parameter) are important for the local evolution of the QBWO in MJ in observations as well as model simulation, whereas advection of planetary vorticity contributes to the westward propagation of QBWO vorticity anomalies in AS. Since the Coriolis parameter f only changes with latitude, this suggests that the correct simulation of anomalous meridional wind is a key factor in the realistic simulation of the QBWO in the model.