bluuebunny/crossref_metadata_2025_split huggingface dataset:
P55 Immunosuppression in the first six weeks following paediatric cardiac transplant
Authors: Thomson Karen , Reinhardt Zdenka 
Published: August 2020

AimThe aim of this audit was to establish whether immunosuppression was being prescribed correctly and whether target levels were being reached during the first six weeks post-transplant.1 2MethodThe standards were discussed and agreed, due to an absence of standardised local or national written protocols, with the lead paediatric cardiothoracic transplant consultant and a specialist transplant liaison nurse. The paediatric transplant database provided a list of patients between October 2016 and July 2018, from which paediatric cardiac transplant patients were included in this audit. All data were collected retrospectively, for the first six weeks post-transplant, from patient’s electronic records.ResultsTwenty-three patients were included in the audit; fifteen males and eight females and the mean age was 6 years old. The standards for the timing and dosing of the first ciclosporin dose were met for 87% and 78% of patients respectively. Six patients (26%) had a ciclosporin level within the target range by day 4 post-transplant, for the remaining seventeen patients the average was day 9 post-transplant. The mean levels remained within this range or slightly above after day 9. Azathioprine or mycophenolate was started within 7 days of transplant in 6 patients (23%). Four patients (17%) had documented episodes of rejection; in one patient all other standards were met and in the other three only one additional standard was not met. Nineteen patients (83%) did not have a documented episode of rejection.ConclusionsPost-transplant management is individualised based on multiple factors such as clinical conditions e.g. renal/liver impairment and whether other agents such as ATG or steroids are being used.1 The lack of documentation around the treatment decisions made it difficult to explain deviations from standards in this audit. Ciclosporin standards were not met completely but were most likely unfeasible due to a narrow target range and the time between first dose and level monitoring. There did not appear to be a clear association between standards not being met and episodes of rejection. It would be beneficial to repeat this as a larger, prospective audit using revised standards.ReferencesCostanzo MR, Costanzo MR, Dipchand A, et al. The international society of heart and lung transplantation guidelines for the care of heart transplant recipients. J Heart Lung Transplant 2010;29:914–56.Sandimmun Concentrate for Solution for Infusion 50 mg/ml - Summary of Product Characteristics (SmPC) - (eMC) [Internet]. [cited 2018 Sep 2]. Available from: https://www.medicines.org.uk/emc/product/1036
P57 Continuous drug delivery is significantly affected by relative height changes between patient and syringe driver
Authors: Zahid Aisha , Wignell Andrew , Raffaj Dusan , Davies Patrick 
Published: August 2020

AimsSyringe drivers are the principle method of giving continuous infusions of important drugs to patients. Many of these drugs are critical for the maintenance of normal physiology. Anecdotal evidence abounds of severe patient instability on movement of syringe drivers during infusion. Our objective was to define the variation in drug delivery seen in three different syringe drivers, with changes in relative height between the syringe driver and the end of the giving set.MethodsThree syringe drivers (Alaris CC (Becton Dickinson), Perfusor Space (B Braun), and Synamed μSP6000 (Arcomed)) were analysed for reliability of flow at 0.5, 1, 2, and 5 ml/hr. A small air bubble was introduced into the giving set, and the progression of this was documented before and after a vertical movement of the syringe driver by 25 or 50 cm upwards or downwards relative to the delivery port.ResultsFor all pumps, delivery was interrupted on movement of the pumps downwards, and a bolus was given with movement of the pump upwards. Delivery halted at lower pump speeds for longer than higher pump speeds. The maximum delivery interruption was 11.8 minutes. Boluses given on moving the pump up were calculated as the equivalent number of minutes needed to deliver the bolus volume at steady state. The maximum bolus given was equivalent to 15.8 minutes of delivery. We were unable to eliminate the effects seen by very slow, steady movement of the pumps up or down. Static height differences made no difference to delivery.ConclusionsSyringe drivers should not be moved vertically in relation to the patient. Critical drug delivery is interrupted for up to 12 minutes with relative downward movements, and significant boluses of drugs are given with relative upward movements. As far as possible, elimination of relative height movements is advised, and extreme caution is necessary if any movements are unavoidable.
Retinal ultra-wide-field colour imaging versus dilated fundus examination to screen for sickle cell retinopathy
Authors: Alabduljalil Talal , Cheung Crystal SY , VandenHoven Cynthia , Mackeen Leslie D , Kirby-Allen Melanie , Kertes Peter J , Lam Wai-Ching 
Published: August 2020

PurposeTo compare ultra-wide-field colour fundus imaging (UWFI) to dilated fundus examination (DFE) for the screening of sickle cell retinopathy (SCR).DesignThis study is a prospective, blinded, multicentre case series.ParticipantsThis study included two groups: an adult group (n=268 eyes) and a paediatric group (n=168 eyes). Sickle cell disease (SCD) types included haemoglobin S homozygous (HbSS), haemoglobin S and C (HbSC) and Hb S with β-thalassaemia (HbSß-Thal).MethodsParticipants underwent DFE and UWFI. Each eye received three independent grades (1–4), documented by three graders: clinical grader, image grader 1 and image grader 2. Three clinically relevant diagnostic thresholds were determined. Based on these thresholds, the sensitivity, specificity, positive predictive value and negative predictive value for all three graders were calculated relative to each other as reference tests.ResultsHbSC was associated with the most advanced SCR grades. When compared to the clinical grader, image grader 1 and image grader 2 consistently detected more SCR and higher SCR grades in both adult and paediatric groups. In both groups, image grader 1 and image grader 2 identified twice as many cases of capillary occlusion/anastomosis than clinical grader. To detect the presence of any proliferative SCR, image grader 1 and image grader 2 had a sensitivity of 82%, 71% in the paediatrics group and 90% and 72% in the adult group. The clinical grader sensitivity was 52% in the paediatrics group and 53% in the adult group.ConclusionThe UWFI is a sensitive tool to screen for SCR. It is superior to DFE in detecting capillary occlusion or anastomosis.
Effectiveness of honey for symptomatic relief in upper respiratory tract infections: a systematic review and meta-analysis
Authors: Abuelgasim Hibatullah , Albury Charlotte , Lee Joseph 
Published: August 2020

BackgroundAntibiotic over prescription for upper respiratory tract infections (URTIs) in primary care exacerbates antimicrobial resistance. There is a need for effective alternatives to antibiotic prescribing. Honey is a lay remedy for URTIs, and has an emerging evidence base for its use. Honey has antimicrobial properties, and guidelines recommended honey for acute cough in children.ObjectivesTo evaluate the effectiveness of honey for symptomatic relief in URTIs.MethodsA systematic review and meta-analysis. We searched Pubmed, Embase, Web of Science, AMED, Cab abstracts, Cochrane Library, LILACS, and CINAHL with a combination of keywords and MeSH terms.ResultsWe identified 1345 unique records, and 14 studies were included. Overall risk of bias was moderate. Compared with usual care, honey improved combined symptom score (three studies, mean difference −3.96, 95% CI −5.42 to −2.51, I2=0%), cough frequency (eight studies, standardised mean difference (SMD) −0.36, 95% CI −0.50 to −0.21, I2=0%) and cough severity (five studies, SMD −0.44, 95% CI −0.64 to −0.25, I2=20%). We combined two studies comparing honey with placebo for relieving combined symptoms (SMD −0.63, 95% CI −1.44 to 0.18, I2=91%).ConclusionsHoney was superior to usual care for the improvement of symptoms of upper respiratory tract infections. It provides a widely available and cheap alternative to antibiotics. Honey could help efforts to slow the spread of antimicrobial resistance, but further high quality, placebo controlled trials are needed.PROSPERO registration NoStudy ID, CRD42017067582 on PROSPERO: International prospective register of systematic reviews (https://www.crd.york.ac.uk/prospero/).
Analysis of reports of unintended pregnancies associated with the combined use of non-enzyme-inducing antibiotics and hormonal contraceptives
Authors: Aronson Jeffrey K , Ferner Robin E 
Published: August 2020

BackgroundEnzyme-inducing antibacterial drugs can impair the efficacy of hormonal contraceptives. Suspicion that other antibiotics might do likewise led to advice that extra contraceptive precautions should be taken during a course of antibiotics. However, current advice is that the purported interaction does not occur, based on small studies observing few pregnancies, assuming that all women are susceptible, and without measuring unbound hormone concentrations.ObjectiveTo test the null hypothesis that antibiotics do not impair the effectiveness of oral contraceptives.DesignA database review of Yellow Card reports to the UK’s Medicines and Healthcare products Regulatory Agency.DataSpontaneous reports of suspected adverse drug reactions in people taking antibacterial drugs (n=74 623), enzyme-inducing medicines (n=32 872), or control medicines (n=65 578).Main outcome measuresReports of the primary outcome—unintended pregnancies; reports of cardiac arrhythmias and headaches (control events); reports of congenital abnormalities (positive control events); and reports of diarrhoea (a possible confounding factor).ResultsCompared with control medicines, unintended pregnancies were seven times more commonly reported with antibiotics and 13 times more commonly reported with enzyme inducers (the positive controls). Congenital abnormalities were reported seven times more often with enzyme inducers but were not more common with antibiotics. Diarrhoea was not a confounding factor.ConclusionThis study provides a signal that antibacterial drugs may reduce the efficacy of hormonal contraceptives. Women taking hormonal contraceptives should be warned that antibiotics may impair their effectiveness. Extra precautions can be taken during a course of antibiotics; an unintended pregnancy is a life-changing event.
Heterogeneity of outcomes for intraoperative music interventions: a scoping review and evidence map
Authors: Ambler Melanie , Springs Stacey , Garcia Dioscaris , Born Christopher 
Published: August 2020

BackgroundOver the past 30 years, numerous studies have been performed that assess the efficacy of intraoperative music as an adjunctive means to regional and local anaesthesia to improve clinical outcomes. Despite an emerging body of evidence and growing adoption of music in surgical settings, the variety of interventions studied, and the heterogeneity of outcomes and outcome measurement tools applied makes difficult the task of aggregating evidence.ObjectiveThis study assesses the state of the field of intraoperative musical interventions by documenting and visualising the breadth of outcomes measured in studies.DesignScoping review and evidence map.MethodsThree electronic databases (PubMed, Embase and a music-focussed research database, RILM (International Music Literature Repository)) were searched for full-text articles published between January 1991 and July 2019. Results from these searches were screened and relevant data was extracted from full-text articles on type of music intervention and type of anaesthesia; outcomes measured were recorded in an evidence map in order to identify the current state of the field and assess for trends in outcome measurements.InterventionsMusic administered to adult patients via headphones or speakers under regional or local sedation in during the intraoperative period.ResultsTwenty-one studies with a total of 2283 patients were included. A total of 42 unique outcomes were measured across the 21 studies, with each measuring an average of 6.41±2.63 outcomes. Systolic blood pressure, diastolic blood pressure, heart rate, anxiety, pain, patient satisfaction, respiratory rate and sedation requirements were the most prevalent outcomes reported. Only 15 outcome measures (36%) were used in more than one study, while the remaining 27 outcome measures (64%) were identified in only one study in our review.ConclusionsOur scoping review identifies that almost two-thirds of studies in this field used>1 outcome measure unique to that study (not also used in other studies), which hinders opportunities to aggregate data across studies and meta-analyse evidence. Future studies should provide clear documentation regarding the intervention and consider using valid and reliable outcome tools. Researchers should consider standardisation when appropriate and adopting the use of core outcome sets for conditions where these sets have been developed.
Two concurrent embryonal rhabdomyosarcomas of the oesophageal and perilaryngeal tissue in an adult dog: imaging, cytological and histological features
Authors: Gombert Alexis , Culang Deborah , Lanthier Isabelle , Martin Edouard , Finck Cyrielle 
Published: August 2020

SUMMARYA five‐year‐old neutered male Labrador Retriever was presented for recurring severe dyspnoeic episodes. Oral examination performed under sedation revealed a mass originating from the left arytenoid. CT highlighted a large perilaryngeal soft‐tissue mass abutting the oesophagus, with a small intralaryngeal component. The mass created a narrowing of the laryngeal lumen and displaced the cranial cervical oesophagus dorsally and to the right. CT also highlighted a second smaller mass rostrally at the level of an oesophageal outpouching, narrowing the caudal aspect of the nasopharynx. The perilaryngeal mass was aspirated under ultrasound guidance. Cytology was suggestive of a tumour arising from skeletal muscle and a rhabdomyosarcoma was suspected. Due to poor prognosis, the patient was euthanased. Postmortem examination confirmed two masses affecting the cranial cervical oesophagus, one of which also invaded the perilaryngeal tissue. Histology and immunohistochemistry provided a final diagnosis of two concurrent oesophageal and perilaryngeal embryonal rhabdomyosarcomas.
Cardiorespiratory demands of competitive rock climbing
Authors: Callender Nigel A. , Hayes Tara N. , Tiller Nicholas B. 
Published: August 2020

Rock climbing has become a mainstream sport, contested on the Olympic stage. The work/rest pattern of bouldering is unique among disciplines, and little is known about its physiological demands. This study characterised the cardiorespiratory responses to simulated competition. Eleven elite boulderers (7 male) volunteered to participate (age = 23.3 ± 4.5 years; mass = 68.2 ± 9.7 kg; stature = 1.73 ± 0.06 m; body fat = 10.4% ± 5%). Subjects completed incremental treadmill running to determine maximal capacities. On a separate day, they undertook a simulated Olympic-style climbing competition comprising 5 boulder problems, each separated by 5 min of rest. Pulmonary ventilation, gas exchange, and heart rate were assessed throughout. Total climbing time was 18.9 ± 2.7 min. Bouldering elicited a peak oxygen uptake of 35.8 ± 7.3 mL·kg−1·min−1 (∼75% of treadmill maximum) and a peak heart rate of 162 ± 14 beats·min−1 (∼88% of maximum). Subjects spent 22.9% ± 8.6% of climbing time above the gas exchange threshold. At exercise cessation, there was an abrupt and significant increase in tidal volume (1.4 ± 0.4 vs. 1.8 ± 0.4 L; p = 0.006, d = 0.83) despite unchanged minute ventilation. Cardiorespiratory parameters returned to baseline within 4 min of the rest period. In conclusion, competitive bouldering elicits substantial cardiorespiratory demand and evidence of tidal volume constraint. Further studies are warranted to explore the effect of cardiorespiratory training on climbing performance. Novelty: Competitive bouldering evokes a high fraction of maximal oxygen uptake and prolonged periods above the gas exchange threshold. Climbing appears to impose a constraint on tidal volume expansion. Cardiorespiratory indices in elite climbers return to baseline within 2–4 min.
National mapping and estimation of forest area by dominant tree species using Sentinel-2 data
Authors: Breidenbach Johannes , Waser Lars T. , Debella-Gilo Misganu , Schumacher Johannes , Rahlf Johannes , Hauglin Marius , Puliti Stefano , Astrup Rasmus 
Published: August 2020

Nation-wide Sentinel-2 mosaics were used with National Forest Inventory (NFI) plot data for modelling and subsequent mapping of spruce-, pine-, and deciduous-dominated forest in Norway at a 16 m × 16 m resolution. The accuracies of the best model ranged between 74% for spruce and 87% for deciduous forest. An overall accuracy of 90% was found on stand level using independent data from more than 42 000 stands. Errors mostly resulting from a forest mask reduced the model accuracies by ∼10%. The produced map was subsequently used to generate model-assisted (MA) and poststratified (PS) estimates of species-specific forest area. At the national level, efficiencies of the estimates increased by 20% to 50% for MA and up to 90% for PS. Greater minimum numbers of observations constrained the use of PS. For MA estimates of municipalities, efficiencies improved by up to a factor of 8 but were sometimes also less than 1. PS estimates were always equally as or more precise than direct and MA estimates but were applicable in fewer municipalities. The tree species prediction map is part of the Norwegian forest resource map and is used, among others, to improve maps of other variables of interest such as timber volume and biomass.
ERK1/2 Signaling Induces Upregulation of ANGPT2 and CXCR4 to Mediate Liver Metastasis in Colon Cancer
Authors: Urosevic Jelena , Blasco María Teresa , Llorente Alicia , Bellmunt Anna , Berenguer-Llergo Antoni , Guiu Marc , Cañellas Adrià , Fernandez Esther , Burkov Ivan , Clapés Maria , Cartanà Mireia , Figueras-Puig Cristina , Batlle Eduard , Nebreda Angel R. , Gomis Roger R. 
Published: August 2020

Abstract

Carcinoma development in colorectal cancer is driven by genetic alterations in numerous signaling pathways. Alterations in the RAS-ERK1/2 pathway are associated with the shortest overall survival for patients after diagnosis of colorectal cancer metastatic disease, yet how RAS–ERK signaling regulates colorectal cancer metastasis remains unknown. In this study, we used an unbiased screening approach based on selection of highly liver metastatic colorectal cancer cells in vivo to determine genes associated with metastasis. From this, an ERK1/2-controlled metastatic gene set (EMGS) was defined. EMGS was associated with increased recurrence and reduced survival in patients with colorectal cancer tumors. Higher levels of EMGS expression were detected in the colorectal cancer subsets consensus molecular subtype (CMS)1 and CMS4. ANGPT2 and CXCR4, two genes within the EMGS, were subjected to gain-of-function and loss-of-function studies in several colorectal cancer cell lines and then tested in clinical samples. The RAS–ERK1/2 axis controlled expression of the cytokine ANGPT2 and the cytokine receptor CXCR4 in colorectal cancer cells, which facilitated development of liver but not lung metastases, suggesting that ANGPT2 and CXCR4 are important for metastatic outgrowth in the liver. CXCR4 controlled the expression of cytokines IL10 and CXCL1, providing evidence for a causal role of IL10 in supporting liver colonization. In summary, these studies demonstrate that amplification of ERK1/2 signaling in KRAS-mutated colorectal cancer cells affects the cytokine milieu of the tumors, possibly affecting tumor–stroma interactions and favoring liver metastasis formation.

Significance:
These findings identify amplified ERK1/2 signaling in KRAS-mutated colorectal cancer cells as a driver of tumor–stroma interactions that favor formation of metastases in the liver.
STAT3 and GR Cooperate to Drive Gene Expression and Growth of Basal-Like Triple-Negative Breast Cancer
Authors: Conway Megan E. , McDaniel Joy M. , Graham James M. , Guillen Katrin P. , Oliver Patsy G. , Parker Stephanie L. , Yue Peibin , Turkson James , Buchsbaum Donald J. , Welm Bryan E. , Myers Richard M. , Varley Katherine E. 
Published: August 2020

Abstract

Breast cancers are divided into subtypes with different prognoses and treatment responses based on global differences in gene expression. Luminal breast cancer gene expression and proliferation are driven by estrogen receptor alpha, and targeting this transcription factor is the most effective therapy for this subtype. By contrast, it remains unclear which transcription factors drive the gene expression signature that defines basal-like triple-negative breast cancer, and there are no targeted therapies approved to treat this aggressive subtype. In this study, we utilized integrated genomic analysis of DNA methylation, chromatin accessibility, transcription factor binding, and gene expression in large collections of breast cancer cell lines and patient tumors to identify transcription factors responsible for the basal-like gene expression program. Glucocorticoid receptor (GR) and STAT3 bind to the same genomic regulatory regions, which were specifically open and unmethylated in basal-like breast cancer. These transcription factors cooperated to regulate expression of hundreds of genes in the basal-like gene expression signature, which were associated with poor prognosis. Combination treatment with small-molecule inhibitors of both transcription factors resulted in synergistic decreases in cell growth in cell lines and patient-derived organoid models. This study demonstrates that GR and STAT3 cooperate to regulate the basal-like breast cancer gene expression program and provides the basis for improved therapy for basal-like triple-negative breast cancer through rational combination of STAT3 and GR inhibitors.

Significance:
This study demonstrates that GR and STAT3 cooperate to activate the canonical gene expression signature of basal-like triple-negative breast cancer and that combination treatment with STAT3 and GR inhibitors could provide synergistic therapeutic efficacy.