bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does initial postgraduate career intention and social demographics predict perceived career behaviour? A national cross-sectional survey of UK postgraduate doctors
Authors: Scanlan Gillian Marion , Cleland Jennifer , Stirling Suzanne Anderson , Walker Kim , Johnston Peter 
Published: August 2019

ObjectiveStudies indicate that initial career intentions and personal characteristics (eg, gender) can influence medical career decision-making. However, little is known about how personal characteristics and intention interact with career decision-making. To address this gap, we examined the link between career intention at the start of the 2-year UK Foundation Programme (FP) and career intentions on its completion.MethodsData came from the 2017 UK National Career Destination Survey, a cross-sectional study completed by all second year foundation doctors. We included respondents’ demographics (gender, graduate status on entry to medical school, career intention on starting the FP) and career intention as an outcome measure (eg, specialty (residency) training (UK), NHS non-training posts/further study, career break, working abroad). Multinomial regression was used to assess the independent relationship between background characteristics and career intention.ResultsThere were 6890 participants and 5570 usable responses. 55.9% of respondents were female and 43.1% were male, 77.1% were non-graduates and 22.9% were graduate entrants to medical school. Approximately two-thirds (62.3%, n=2170) of doctors who had an original intention to pursue specialty training after F2, still intended to do so on completion. Most of those who stated at the start of F2 that they did not want to pursue specialty indicated at the end of F2 they would be undertaking other employment opportunities outwith formal training. However, 37.7% of respondents who originally intended to pursue specialty training on FP completion did something different. Graduate entrants to medicine were more likely to immediately progress into specialty training compared with their peers who did medicine as a primary first degree.ConclusionOriginal intention is a strong predictor of career intentions at the end of the FP. However, a considerable proportion of doctors changed their mind during the FP. Further research is needed to understand this behaviour.
Is an obesity simulation suit in an undergraduate medical communication class a valuable teaching tool? A cross-sectional proof of concept study
Authors: Herrmann-Werner Anne , Loda Teresa , Wiesner Lisa M , Erschens Rebecca Sarah , Junne Florian , Zipfel Stephan 
Published: August 2019

ObjectiveWith the growing prevalence of overweight and obesity, medical students should be prepared to engage in weight management and obesity-related communications in order to prevent patients from having stigmatising experiences. In addition, medical students should have training to reduce anti-fat prejudices.DesignCross-sectional proof of concept study.SettingUniversity Hospital Tuebingen, Germany.Participants246 participants (207 second-year medical students, 13 standardised patients (SPs) and 22 teachers) took part in the study.Primary and secondary outcome measuresThe primary outcome was the assessment of degree of reality of the encounter with the SP wearing an obesity simulation suit (OSS). The secondary outcome was the evaluation of students’ awareness and prejudice against patients with obesity in a simulated role play. Additionally, a description of the advantages and disadvantages when using such a teaching tool is delivered.ResultsThe OSS contributed to a realistic perception of the patient group depicted in a role play according to students, teachers and SPs. OSS body mass index estimation by students, teachers and SPs correctly was over 30 kg/m2—thus in the range of obesity. In a selected subscale of the Anti-Fat Attitudes Test, students showed significantly stronger anti-fat stigmatisation compared with teachers and SPs.ConclusionsAn OSS worn by an SP is a valuable teaching tool to raise awareness about patients with obesity. It gives a realistic picture of the encounter. Stigmatisation was low in general but was especially present in the students. Further research should include intervention studies to address this issue.
Effects of high-intensity interval training and nutrition advice on cardiometabolic markers and aerobic fitness in adolescent girls with obesity
Authors: Plavsic Ljiljana , Knezevic Olivera M. , Sovtic Aleksandar , Minic Predrag , Vukovic Rade , Mazibrada Ilijana , Stanojlovic Olivera , Hrncic Dragan , Rasic-Markovic Aleksandra , Macut Djuro 
Published: August 2019

The aim of the study was to compare the effects of high-intensity interval training (HIIT) and nutrition advice on cardiometabolic biomarkers, hormonal parameters, and cardiorespiratory fitness in adolescent girls with obesity. Adolescent girls with obesity (n = 44, aged 13–19 years) were randomized into a 12-week intervention as follows: (i) dietary advice and HIIT (n = 22), and (ii) dietary advice only (n = 22). The concentration of biomarkers of inflammation, biochemical and hormonal testing, oral glucose tolerance test, cardiorespiratory fitness, physical activity levels, and nutrition were assessed. After a 3-month intervention, the diet+HIIT group significantly increased insulin sensitivity index (–0.34 ± 1.52 vs. 1.05 ± 3.21; p = 0.001) and work load (0.6 ± 11.3 W vs. 14.6 ± 20.2 W; p = 0.024) and decreased glucose area under the curve (–0.29 ± 4.69 vs. −0.98 ± 4.06; p = 0.040), insulin area under the curve (−9.65 ± 117.9 vs. −98.7 ± 201.8; p = 0.003), and high-sensitivity C-reactive protein (hs-CRP) (0.12 ± 1.92 mg/L vs. −1.47 ± 3.67 mg/L; p = 0.039) in comparison with the diet group. Regarding within-group changes, both groups had significant improvements in body mass index (BMI), BMI-standard deviation score, body fat percentage, and systolic blood pressure. Positive impact on waist circumference, waist circumference/height ratio, diastolic blood pressure, hs-CRP, work load, maximal heart rate, and resting heart rate was observed only after the diet+HIIT intervention. No significant change was noted in peak oxygen uptake, lipid profile, and hormonal parameters between groups after intervention. Novelty HIIT and nutrition advice increased insulin sensitivity and decreased BMI, body fat, systolic blood pressure, and diastolic blood pressure. Nutrition advice decreased BMI, body fat, and systolic blood pressure in adolescent girls with obesity.
Identification of Coding and Long Noncoding RNAs Differentially Expressed in Tumors and Preferentially Expressed in Healthy Tissues
Authors: Unfried Juan P. , Serrano Guillermo , Suárez Beatriz , Sangro Paloma , Ferretti Valeria , Prior Celia , Boix Loreto , Bruix Jordi , Sangro Bruno , Segura Víctor , Fortes Puri 
Published: August 2019

AbstractThe Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets allow unprecedented gene expression analyses. Here, using these datasets, we performed pan-cancer and pan-tissue identification of coding and long noncoding RNA (lncRNA) transcripts differentially expressed in tumors and preferentially expressed in healthy tissues and/or tumors. Pan-cancer comparison of mRNAs and lncRNAs showed that lncRNAs were deregulated in a more tumor-specific manner. Given that lncRNAs are more tissue-specific than mRNAs, we identified healthy tissues that preferentially express lncRNAs upregulated in tumors and found that testis, brain, the digestive tract, and blood/spleen were the most prevalent. In addition, specific tumors also upregulate lncRNAs preferentially expressed in other tissues, generating a unique signature for each tumor type. Most tumors studied downregulated lncRNAs preferentially expressed in their tissue of origin, probably as a result of dedifferentiation. However, the same lncRNAs could be upregulated in other tumors, resulting in "bimorphic" transcripts. In hepatocellular carcinoma (HCC), the upregulated genes identified were expressed at higher levels in patients with worse prognosis. Some lncRNAs upregulated in HCC and preferentially expressed in healthy testis or brain were predicted to function as oncogenes and were significantly associated with higher tumor burden, and poor prognosis, suggesting their relevance in hepatocarcinogenesis and/or tumor evolution. Taken together, therapies targeting oncogenic lncRNAs should take into consideration the healthy tissue, where the lncRNAs are preferentially expressed, to predict and decrease unwanted secondary effects and increase potency.Significance:Comprehensive analysis of coding and noncoding genes expressed in different tumors and normal tissues, which should be taken into account to predict side effects from potential coding and noncoding gene-targeting therapies.
Cellular and Genetic Determinants of the Sensitivity of Cancer to α-Particle Irradiation
Authors: Yard Brian D. , Gopal Priyanka , Bannik Kristina , Siemeister Gerhard , Hagemann Urs B. , Abazeed Mohamed E. 
Published: August 2019

Abstract

Targeted α-particle–emitting radionuclides have great potential for the treatment of a broad range of cancers at different stages of progression. A platform that accurately measures cancer cellular sensitivity to α-particle irradiation could guide and accelerate clinical translation. Here, we performed high-content profiling of cellular survival following exposure to α-particles emitted from radium-223 (223Ra) using 28 genetically diverse human tumor cell lines. Significant variation in cellular sensitivity across tumor cells was observed. 223Ra was significantly more potent than sparsely ionizing irradiation, with a median relative biological effectiveness of 10.4 (IQR: 8.4–14.3). Cells that are the most resistant to γ radiation, such as Nrf2 gain-of-function mutant cells, were sensitive to α-particles. Combining these profiling results with genetic features, we identified several somatic copy-number alterations, gene mutations, and the basal expression of gene sets that correlated with radiation survival. Activating mutations in PIK3CA, a frequent event in cancer, decreased sensitivity to 223Ra. The identification of cellular and genetic determinants of sensitivity to 223Ra may guide the clinical incorporation of targeted α-particle emitters in the treatment of several cancer types.

Significance:
These findings address limitations in the preclinical guidance and prediction of radionuclide tumor sensitivity by identifying intrinsic cellular and genetic determinants of cancer cell survival following exposure to α-particle irradiation.
See related commentary by Sgouros, p. 5479
Synthetic Lethal Interactions for Kinase Deficiencies to DNA Damage Chemotherapeutics
Authors: Robinson-Garcia Lydia , Ferreira da Silva Joana , Loizou Joanna I. 
Published: August 2019

Abstract
Kinases are signaling enzymes that regulate diverse cellular processes. As such, they are frequently mutated in cancer and therefore represent important targets for drug discovery. However, until recently, systematic approaches to identify vulnerabilities and resistances of kinases to DNA-damaging chemotherapeutics have not been possible, partially due to the lack of appropriate technologies. With the advent of CRISPR-Cas9, a comprehensive study has investigated the cellular survival of more than 300 kinase-deficient isogenic cell lines to a diverse panel of DNA-damaging agents, enriched for chemotherapeutics. Here, we discuss how this approach has allowed for the rational development of combination therapies that are aimed at using synthetic lethal interactions between kinase deficiencies and DNA-damaging agents that are used as chemotherapeutics.
Financial Incentives to Promote Colorectal Cancer Screening: A Longitudinal Randomized Control Trial
Authors: Lieberman Alicea , Gneezy Ayelet , Berry Emily , Miller Stacie , Koch Mark , Ahn Chul , Balasubramanian Bijal A. , Argenbright Keith E. , Gupta Samir 
Published: August 2019

Abstract

Background:
Financial incentives may improve health behaviors. We tested the impact of offering financial incentives for mailed fecal immunochemical test (FIT) completion annually for 3 years.

Methods:
Patients, ages 50 to 64 years, not up-to-date with screening were randomized to receive either a mailed FIT outreach (n = 6,565), outreach plus $5 (n = 1,000), or $10 (n = 1,000) incentive for completion. Patients who completed the test were reinvited using the same incentive the following year, for 3 years. In year 4, patients who returned the kit in all preceding 3 years were reinvited without incentives. Primary outcome was FIT completion among patients offered any incentive versus outreach alone each year. Secondary outcomes were FIT completion for groups offered $5 versus outreach alone, $10 versus outreach alone, and $5 versus $10.

Results:
Year 1 FIT completion was 36.9% with incentives versus 36.2% outreach alone (P = 0.59) and was not statistically different for $10 (34.6%; P = 0.31) or $5 (39.2%; P = 0.070) versus outreach alone. Year 2 completion was 61.6% with incentives versus 60.8% outreach alone (P = 0.75) and not statistically different for $10 or $5 versus outreach alone. Year 3 completion was 79.4% with incentives versus 74.8% outreach alone (P = 0.080), and was higher for $10 (82.4%) versus outreach alone (P = 0.033), but not for $5 versus outreach alone. Completion was similar across conditions in year 4 (no incentives).

Conclusions:
Offering small incentives did not increase FIT completion relative to standard outreach.

Impact:
This was the first longitudinal study testing the impact of repeated financial incentives, and their withdrawal, on FIT completion.
Urinary PGE-M Levels and Risk of Ovarian Cancer
Authors: Barnard Mollie E. , Beeghly-Fadiel Alicia , Milne Ginger L. , Akam Eftitan Y. , Chan Andrew T. , Eliassen A. Heather , Rosner Bernard A. , Shu Xiao-Ou , Terry Kathryn L. , Xiang Yong-Bing , Zheng Wei , Tworoger Shelley S. 
Published: August 2019

Abstract

Background:
Regular aspirin use may lower ovarian cancer risk by blocking the cyclooxygenase enzymes, resulting in lower expression of prostaglandins, including prostaglandin E2 (PGE2). We evaluated whether higher prediagnosis PGE-M (a urinary biomarker of PGE2) was associated with increased ovarian cancer risk in three prospective cohorts.

Methods:
We conducted a case–control study nested in the Nurses' Health Study (NHS), NHSII, and Shanghai Women's Health Study. Our analyses included 304 cases of epithelial ovarian cancer diagnosed from 1996 to 2015 and 600 matched controls. We measured urinary PGE-M using LC/MS with normalization to creatinine. Measures from each study were recalibrated to a common standard. We estimated ORs and 95% confidence intervals (CI) using conditional logistic regression, with PGE-M levels modeled in quartiles. Multivariable models were adjusted for ovarian cancer risk factors.

Results:
There was no evidence of an association between urinary PGE-M levels and ovarian cancer risk for women with PGE-M levels in the top versus bottom quartile (OR = 0.80; 95% CI, 0.51–1.27; Ptrend = 0.37). We did not observe heterogeneity by histotype (P = 0.53), and there was no evidence of effect modification by body mass index (Pinteraction = 0.82), aspirin use (Pinteraction = 0.59), or smoking (Pinteraction = 0.14).

Conclusions:
Prediagnosis urinary PGE-M levels were not significantly associated with ovarian cancer risk. Larger sample sizes are needed to consider a more modest association and to evaluate associations for specific tumor subtypes.

Impact:
Systemic prostaglandin levels do not appear strongly associated with ovarian cancer risk. Future research into aspirin use and ovarian cancer risk should consider local prostaglandins and prostaglandin-independent mechanisms.
Assessing Metabolic Intervention with a Glutaminase Inhibitor in Real-Time by Hyperpolarized Magnetic Resonance in Acute Myeloid Leukemia
Authors: Zacharias Niki M. , Baran Natalia , Shanmugavelandy Sriram S. , Lee Jaehyuk , Lujan Juliana Velez , Dutta Prasanta , Millward Steven W. , Cai Tianyu , Wood Christopher G. , Piwnica-Worms David , Konopleva Marina , Bhattacharya Pratip K. 
Published: August 2019

Abstract
Acute myeloid leukemia (AML) is an aggressive hematopoietic disease characterized by glutamine-dependent metabolism. A novel glutaminase (GLS) inhibitor, CB-839, is currently under evaluation for treatment of hematopoietic malignancies and solid tumors. Our purpose was to measure cellular changes in AML associated with CB-839 treatment and to test the ability of hyperpolarized pyruvate for interrogating these changes to OCI-AML3 cells. Our results show that treatment with CB-839 interfered with the citric acid cycle, reduced the NADH/NAD+ ratio and ATP levels, reduced cell proliferation and viability, and reduced the basal and maximal respiratory capacities [oxygen consumption rate (OCR)]. We observed a reduction of the conversion of hyperpolarized pyruvate to lactate in cell lines and in a mouse AML model after CB-839 treatment. Our in vitro and in vivo results support the hypothesis that, in AML, glutamine is utilized to generate reducing equivalents (NADH, FADH2) through the citric acid cycle and that reduction in redox state by GLS inhibition decreases the rate of pyruvate to lactate conversion catalyzed by lactate dehydrogenase. We propose hyperpolarized pyruvate/lactate measurement as a method for direct monitoring of metabolic changes occurring in AML patients receiving CB-839. With further optimization, this method may provide a noninvasive imaging tool to assess the early efficacy of therapeutic intervention with GLS inhibitors.
Eclipse across America: Citizen Science Observations of the 21 August 2017 Total Solar Eclipse
Authors: Dodson J. Brant , Robles Marilé Colón , Taylor Jessica E. , DeFontes Cayley C. , Weaver Kristen L. 
Published: August 2019

AbstractOn 21 August 2017, North America witnessed a total solar eclipse, with the path of totality passing across the United States from coast to coast. The major public interest in the event inspired the Global Learning and Observations to Benefit the Environment (GLOBE) Observer to organize a citizen science observing campaign to record the meteorological effects of the eclipse. Participants at 17 585 observing sites collected 68 620 temperature observations and 15 978 cloud observations. With 7194 sites positioned in the path of totality, participants provide a nearly unbroken record of the cloud and temperature effects of the eclipse across the contiguous United States. The collection of both temperature and cloud observations provides an opportunity to quantify the cloud–temperature relationship. The unique character of citizen science, which provides data from a large number of observations with limited quality control, requires a method that leverages the large number of observations. By grouping observing sites along the path of totality by 1° longitude bins, the errors from individual sites are averaged out and the meteorological effects of the eclipse can be determined robustly. The data reveal a distinct relationship between prevailing cloud cover and the eclipse-induced temperature depression, in which overcast conditions reduces the temperature depression by about one-half of the value from clear conditions. A comparison of the GLOBE results with mesonet data allows a test of the robustness of the citizen science results. The results also show the great benefit that research using citizen science data receives from increased numbers of participants and observations.
Precessional Forced Zonal Triple-Pole Anomalies in the Tropical Pacific Annual Cycle
Authors: Wang Yue , Jian ZhiMin , Zhao Ping , Xu Kang , Dang Haowen , Liu ZhongFang , Xiao Dong , Chen JunMing 
Published: August 2019

Abstract
Based on a transient simulation of the Community Earth System Model, we identified two anomalous “zonal triple-pole type” annual cycles in the equatorial Pacific sea surface temperature (SST), which were induced by precessional evolution of the summer-minus-winter insolation difference and the autumn-minus-spring insolation difference, respectively. For example, due to the increased summer–winter insolation contrast, a zonal positive–negative–positive pattern of equatorial SST anomalies was detected after subtracting basin-scale summer SST warming. The positive SST anomalies were associated with anomalous upward air flows over the western Pacific and eastern Pacific, whereas the negative SST anomalies in the central Pacific were coupled with anomalous downward air flows, oceanic upwelling, and thermocline cooling. These central Pacific anomalies were due to multiple air–sea interactions, particularly zonal advection feedback and Bjerknes feedback. This anomalous annual cycle also included winter equatorial air–sea coupled anomalies with similar spatial patterns but opposite signs. The annual mean equatorial rainfall was significantly increased west of 135°E but decreased between 135°E and 160°W in response to the moderately intensified Walker circulation west of 160°W. The autumn–spring insolation contrast induced similar seasonal reversed anomalies during autumn and spring, but the annual means were only weakly enhanced for the Walker circulation and the rainfall anomalies had smaller magnitudes east of 160°E. These distinct responses of the annual mean climate indicated different seasonal biases in terms of the equatorial SST and associated Walker circulation anomalies due to forcing by the two seasonal insolation contrasts, and these findings had meaningful implications for paleoceanographic studies.
A Method for Assessing Relative Skill in Retrieving Cloud and Precipitation Properties in Next-Generation Cloud Radar and Radiometer Orbiting Observatories
Authors: Xu Zhuocan , Mace Gerald G. , Posselt Derek J. 
Published: August 2019

AbstractA Bayesian Markov chain Monte Carlo (MCMC) algorithm is utilized to compare the skill of an A-Train-like observing system with a cloud, convection, and precipitation (CCP) observing system like that contemplated for the 2020s by the 2017 National Academy of Sciences Decadal Survey. The main objective is to demonstrate a framework for observational trade space studies. This initial work focuses on weakly precipitating warm shallow cumulus constructed from in situ data. Radiative computations are based on Mie theory with spherical assumptions. Simulated measurements in the CCP configuration consist of W- and Ka-band radar reflectivity and path-integrated attenuation, 31 and 94 GHz brightness temperatures (Tb), and visible and near-infrared reflectances. The collection of measurements in the CloudSat configuration is identical, but includes a single 94 GHz radar frequency, and the uncertainty in the 94 GHz microwave brightness temperature is increased to mimic the CloudSat Tb product. The experiments demonstrate that it remains a challenge to diagnose cloud properties in the presence of light rain because of the tendency of microwave remote sensing to respond to the higher moments of the hydrometeor populations. Rain properties are significantly better constrained than cloud properties, even in the optimal CCP configuration. The addition of Ka-band measurements places substantial constraints on the precipitation rain effective radius and rain rates. The Tb offers important information regarding the column-integrated condensate mass, the measurement accuracy of which appears more likely to affect the retrievals of clouds with low liquid water path. The constraints provided by reflectances are largely restricted to regions near the cloud top, particularly in the raining cases.