bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients
Authors: Rydbirk Rasmus , Folke Jonas , Busato Florence , Roché Elodie , Chauhan Alisha Shahzad , Løkkegaard Annemette , Hejl Anne-Mette , Bode Matthias , Blaabjerg Morten , Møller Mette , Danielsen Erik Hvid , Brudek Tomasz , Pakkenberg Bente , Tost Jorg , Aznar Susana 
Published: March 2020

AbstractMultiple system atrophy (MSA) is a rare disease with a fatal outcome. To date, little is known about the molecular processes underlying disease development. Its clinical overlap with related neurodegenerative movement disorders underlines the importance for expanding the knowledge of pathological brain processes in MSA patients to improve distinction from similar diseases. In the current study, we investigated DNA methylation changes in brain samples from 41 MSA patients and 37 healthy controls. We focused on the prefrontal cortex, a moderately affected area in MSA. Using Illumina MethylationEPIC arrays, we investigated 5-methylcytosine (5mC) as well as 5-hydroxymethylcytosine (5hmC) changes throughout the genome. We identified five significantly different 5mC probes (adj.P < 0.05), of which one probe mapping to theAREL1gene involved in antigen presentation was decreased in MSA patients. This decrease correlated with increased 5hmC levels. Further, we identified functional DNA methylation modules involved in inflammatory processes. As expected, the decreased 5mC levels onAREL1was concordant with increased gene expression levels of bothAREL1as well as MHC Class IHLAgenes in MSA brains. We also investigated whether these changes in antigen-related processes in the brain associated with changes in peripheral mononuclear cells. Using flow cytometry on an independent cohort of MSA patients, we identified a decrease in circulating non-classical CD14+CD16++blood monocytes, whereas T and NK cell populations were unchanged. Taken together, our results support the view of an active neuroimmune response in brains of MSA patients.
Family related variables effect on later educational outcome: a further geospatial analysis on TIMSS 2015 Finland
Authors: Harju-Luukkainen H. , Vettenranta J. , Wang J. , Garvis S. 
Published: March 2020

AbstractFamily-related factors, like parent’s educational level, their values and expectations have a significant impact on child’s early skills and later educational outcomes. Further, parents provide their child, alongside with other learning environments, a broad mathematical and early literacy input. This study investigates the relationship between family-related socio-economic and other factors like, parental education, amount of books at home, parental attitudes towards mathematics and science, parental perception of child’s early skills and student’s later academic achievement. This is studied in the light of the Finnish data collected for Trends in International Mathematics and Science Study (TIMSS) 2015. The results are presented with the help of a geospatial method called Kriging that reveals regional variance. The results indicate that family-related background variables have different effects on child’s later achievement in mathematics across Finland. The results suggest, that some areas in Finland are better in ‘levelling the playing field’ for children and minimising the effect of family related variables on educational outcomes than others.
Modelling shares choice to enter in a portfolio using artificial neural networks (ANN)
Authors: Manurung Adler Haymans , Natasha Christina , Budiharto Widodo 
Published: March 2020

AbstractShares choice to enter a portfolio is a good topic in finance and management, as it affects the portfolio performance which is managed by a Fund Manager. In this research, we aim to create an artificial neural network model to choose a share to enter a portfolio based on its financial factors and big data about the financial condition of companies. The artificial neural network model has 15 input nodes of attributes associated with a company’s financial situation, 8 hidden layer nodes, and 1 output node. The accuracy of the model is 85.71%, with a learning rate of 0.05 trained over 2000 iterations.
Sleep disturbances and predictors of nondeployability among active-duty Army soldiers: an odds ratio analysis of medical healthcare data from fiscal year 2018
Authors: Devine Jaime K. , Collen Jacob , Choynowski Jake J. , Capaldi Vincent 
Published: March 2020

Abstract
Background
The impact of sleep disorders on active-duty soldiers’ medical readiness is not currently quantified. Patient data generated at military treatment facilities can be accessed to create research reports and thus can be used to estimate the prevalence of sleep disturbances and the role of sleep on overall health in service members. The current study aimed to quantify sleep-related health issues and their impact on health and nondeployability through the analysis of U.S. military healthcare records from fiscal year 2018 (FY2018).

Methods
Medical diagnosis information and deployability profiles (e-Profiles) were queried for all active-duty U.S. Army patients with a concurrent sleep disorder diagnosis receiving medical care within FY2018. Nondeployability was predicted from medical reasons for having an e-Profile (categorized as sleep, behavioral health, musculoskeletal, cardiometabolic, injury, or accident) using binomial logistic regression. Sleep e-Profiles were investigated as a moderator between other e-Profile categories and nondeployability.

Results
Out of 582,031 soldiers, 48.4% (n = 281,738) had a sleep-related diagnosis in their healthcare records, 9.7% (n = 56,247) of soldiers had e-Profiles, and 1.9% (n = 10,885) had a sleep e-Profile. Soldiers with sleep e-Profiles were more likely to have had a motor vehicle accident (pOR (prevalence odds ratio) =4.7, 95% CI 2.63–8.39, P ≤ 0.001) or work/duty-related injury (pOR = 1.6, 95% CI 1.32–1.94, P ≤ 0.001). The likelihood of nondeployability was greater in soldiers with a sleep e-Profile and a musculoskeletal e-Profile (pOR = 4.25, 95% CI 3.75–4.81, P ≤ 0.001) or work/duty-related injury (pOR = 2.62, 95% CI 1.63–4.21, P ≤ 0.001).

Conclusion
Nearly half of soldiers had a sleep disorder or sleep-related medical diagnosis in 2018, but their sleep problems are largely not profiled as limitations to medical readiness. Musculoskeletal issues and physical injury predict nondeployability, and nondeployability is more likely to occur in soldiers who have sleep e-Profiles in addition to these issues. Addressing sleep problems may prevent accidents and injuries that could render a soldier nondeployable.
The novel coronavirus outbreak: what can be learned from China in public reporting?
Authors: Li Hao , Chen Xinguang , Huang Hao 
Published: March 2020

AbstractThe new coronavirus outbreak gets everyone’s attention. China’s national actions against the outbreak have contributed great contributions to the world. China has been learning from practice for better reporting and is fast to adapt itself. In this article we discuss China’s practice in public reporting and its implications to global health. Confirmed cases, dynamic suspected cases, recovered cases, and deaths have been reported both in accumulative numbers and their daily updates. Some ratio indictors reporting (fatality rate, recovery rate, etc.), trend reporting, and global surveillance have been applied as well. Some improvements can still be made. It is necessary to further explore the influential factors behind the indicators for interventions. Recommendations are made to the World Health Organization and other countries for better public reporting and surveillance.
Arterial CO2 pressure changes during hypercapnia are associated with changes in brain parenchymal volume
Authors: van der Kleij Lisa A. , De Vis Jill B. , de Bresser Jeroen , Hendrikse Jeroen , Siero Jeroen C. W. 
Published: March 2020

AbstractThe Monro-Kellie hypothesis (MKH) states that volume changes in any intracranial component (blood, brain tissue, cerebrospinal fluid) should be counterbalanced by a co-occurring opposite change to maintain intracranial pressure within the fixed volume of the cranium. In this feasibility study, we investigate the MKH application to structural magnetic resonance imaging (MRI) in observing compensating intracranial volume changes during hypercapnia, which causes an increase in cerebral blood volume. Seven healthy subjects aged from 24 to 64 years (median 32), 4 males and 3 females, underwent a 3-T three-dimensional T1-weighted MRI under normocapnia and under hypercapnia. Intracranial tissue volumes were computed. According to the MKH, the significant increase in measured brain parenchymal volume (median 6.0 mL; interquartile range 4.5, 8.5; p = 0.016) during hypercapnia co-occurred with a decrease in intracranial cerebrospinal fluid (median -10.0 mL; interquartile range -13.5, -6.5; p = 0.034). These results convey several implications: (i) blood volume changes either caused by disorders, anaesthesia, or medication can affect outcome of brain volumetric studies; (ii) besides probing tissue displacement, this approach may assess the brain cerebrovascular reactivity. Future studies should explore the use of alternative sequences, such as three-dimensional T2-weighted imaging, for improved quantification of hypercapnia-induced volume changes.
Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, 5-fluorouracil and leucovorin in stage III colon cancer
Authors: Bertagnolli M. M. , Compton C. C. , Niedzwiecki D. , Warren R. S. , Jewell S. , Bailey G. P. , Mayer R. J. , Goldberg R. , Saltz L. , Redston M. 
Published: March 2020

10003 Background: Colon cancers exhibiting a high level of microsatellite instability (MSI-H) show distinct clinicopathological features, including both better prognosis and reduced response to 5-fluorouracil (5-FU)-based chemotherapy. We investigated the impact of adjuvant chemotherapy containing irinotecan in patients with MSI-H colon cancers. Methods: CALGB protocol 89803 randomized 1264 patients with resected stage III colon cancer to receive post-operative 5-FU and leucovorin (LV) with or without irinotecan. Paraffin blocks containing primary tumor and normal tissue were collected. Microsatellite instablility was assessed using a panel of mono- and di-nucleotide markers. Disease free survival (DFS) was measured from trial entry until documented disease progression or death from any cause. A statistical significance level of 0.2 was used in screening to generate hypotheses regarding MSI status and outcome. Median follow-up at analysis was 3.8 years. Overall C89803 showed no advantage for addition of irinotecan to 5-FU/LV. Results: Patients with and without tumor samples analyzed did not differ by treatment, age, gender, primary site, T-stage, differentiation, # positive nodes, or mucinous type. Of 482 tumors analyzed, 75 (16%) demonstrated MSI-H. MSI-H cancers were more likely to be located in the proximal colon (p<0.0001), of high histologic grade (p<0.0001) and mucinous histology (p<0.0001), and also had increased numbers of tumor-containing lymph nodes (mean # positive nodes/case = 3.5 for MSI Low/Stable vs. 4.7 for MSI-H; p = 0.04). At the time of analysis 143 of 482 patients (36%) analyzed experienced tumor recurrence and/or death due to any cause. For patients with MSI-H tumors, DFS was better in those treated with irinotecan in addition to 5-FU/LV (logrank p=0.18). Among patients with MSI Low/Stable tumors there was no difference in DFS between those treated with and without irinotecan (logrank p =0.39). Conclusions: Early results from CALGB protocol 89803 indicate that addition of postoperative irinotecan to 5-FU/LV may improve DFS in patients with stage III colon cancers that exhibit MSI-H. Longer follow-up is required to confirm this finding. [Table: see text]
Is mammography adequate for screening BRCA mutation carriers with low breast density?
Authors: Bigenwald R. , Warner E. , Gunasekara A. , Hill K. , Causer P. , Messner S. , Eisen A. , Plewes D. , Narod S. , Yaffe M. 
Published: March 2020

10014 Background: Several large observational studies have demonstrated that magnetic resonance imaging (MRI) is much more sensitive than M (sensitivity 71–96% vs. 28–43%) for screening women > age 25 at high risk for hereditary breast cancer. However, MRI is much more costly and less specific than M. The extent to which the low sensitivity of M in these studies is due to the greater average breast density of younger women is unknown. Accordingly, we sought to determine the sensitivity of M and MRI according to breast density for the detection of breast cancer in a screening study of BRCA mutation carriers. Methods: Breast density was measured on the screening mammogram of the contralateral breast for all women who developed in-situ or invasive breast cancer on study. Density was measured in 2 ways: qualitatively according to the four categories characterized by the BIRADS system: 1) mostly fatty, 2) scattered fibroglandular tissue, 3) heterogeneously dense, 4) extremely dense; and semi-quantitatively using computer-aided techniques with subsequent classification as: A) ≤10%, B) 11–25%, C) 26%-50%, or D) >50% density. Results: Between 11/97 and 06/05 a total of 39 cases (12 in-situ and 27 invasive) were found in 36 mutation carriers (19 BRCA1 and 17 BRCA2). Mean age of the women with cancer was 48 (range 34 to 64). Average semi-quantitative breast density for BRCA1 mutation carriers was 28% and for BRCA2 was 27%. Sensitivity of M vs. MRI for in-situ cases was 25% vs. 83%, and for invasive cases was 30% vs. 93%. Sensitivities for BRCA1 and BRCA2 mutation carriers were similar. For BIRADS 1 to 4 respectively M detected 1/3 (33%), 5/11 (45%), 4/22 (18%), and 1/3 (33%) of cases; and for density groups A to D respectively detected 2/6 (33%), 7/15 (47%), 1/11 (9%) and, 1/7 (14%). Conclusion: Although there was a trend towards decreasing mammographic sensitivity with increasing density, even among BRCA mutation carriers with low breast density mammography is an inadequate screening tool. No significant financial relationships to disclose.
Phase I study of CNF1010 (lipid formulation of 17-(allylamino)-17-demethoxygeldanamycin: 17-AAG) in patients with advanced solid tumors
Authors: Saif M. W. , Erlichman C. , Dragovich T. , Mendelson D. , Toft D. , Timony G. , Burrows F. , Padgett C. , De Jager R. , Von Hoff D. 
Published: March 2020

10062 Background: 17-AAG is a benzoquinone ansamycin that binds to and inhibits the HSP90 family of molecular chaperones leading to the proteasomal degradation of client proteins critical in malignant cell proliferation and survival. We have undertaken a Phase 1 trial of CNF1010, an oil-in-water nanoemulsion of 17-AAG. Methods: Patients (pts) with advanced solid tumors, ECOG PS 0–2, and adequate hematologic, hepatic, renal and cardiac functions received CNF1010 by 1 h intravenous infusion, twice-a-week, three weeks out of four, starting at 6 mg/m2 per dose. Doses were escalated sequentially in single pts (6 and 12 mg/m2) and 3–6 pts (≥ 25 mg/m2) cohorts according to a modified Fibonacci’s schema. Plasma pharmacokinetic (PK) profiles were obtained on days 1 and 18. Biomarkers were measured in PBMC’s (HSP70) and plasma (HER-2 ectodomain (HER-2 ECD)). Results: 30 pts (M/F: 14/16; median age 63, range 48–78) with colorectal cancer (11), pancreatic cancer (5), melanoma (5), ovarian (2), others (7) were treated with a median of 2 courses (range: 1–10). There was no dose-limiting toxicity up to 175 mg/m2. One pt at 175 mg/m2 died on study, but drug relation was unclear. Grade 1–2 gastrointestinal toxicities (nausea, vomiting, diarrhea) and serum creatinine elevation were observed. Severe toxicities (grade 3 but no grade 4) consisted of reversible hepatic enzyme elevation, hyperbilirubinemia, fatigue, anemia and hyperglycemia. There were no hematological toxicities. Plasma 17-AAG PK appeared dose-proportional (AUC, Cmax); CL (17 L/h/m2) and t1/2 (5.2 h) were dose independent and unchanged after repeated dosing (day 18). Post-treatment increases in HSP70 were observed in PBMCs and decreases in plasma HER-2 ECD were observed at doses ≥ 83 mg/m2. Minor tumor regressions were seen in 1 pt with duodenal cancer (83 mg/m2), 1 pt with gastric carcinoid (175 mg/m2) and 1 pt with melanoma (175 mg/m2). Conclusion: The threshold of biologic activity for CNF1010 administered by a twice a week schedule appears to be 83 mg/m2. This dosing regimen appears to be optimal and supported by the pharmacokinetic and pharmacodynamic data. The MTD has not yet been determined. Dose escalation of CNF1010 continues at 225 mg/m2. [Table: see text]
The mutation status of the epidermal growth factor receptor (EGFR) as a selection criterion for therapy with EGFR tyrosine kinase inhibitors (TKI’s) in non-small cell lung cancer (NSCLC)
Authors: Mathy A. , Nederlof P. , Boerrigter L. , Van ’t Veer L. , De Jong D. , Baas P. , Burgers S. , Van Zandwijk N. 
Published: March 2020

10073 Background: Somatic mutations in the EGFR gene have been shown to be closely associated with a favorable response to small-molecule TKI’s, while K-ras mutations seem to be associated with primary resistance. We present an exploratory study confirming the importance of mutation status for response on anti EGFR therapy. Methods: Mutations in the EGFR TK domain were looked for in tumor material extracted from two series of patients with advanced NSCLC. In the first series, mutations were determined in patients with an objective response or clearly progressive under gefitinib therapy. In the second series, EGFR mutations were determined prospectively in an enriched population (two of three characteristics: female gender, non-smoking status, bronchoalveolar -or adenocarcinoma pathology). The presence of a mutation was the criterion for treatment with TKI’s. Response assessment was done according to RECIST. K-Ras mutations were determined retrospectively. Results: In the retrospective series, 15 biopsies were analyzed, belonging to 3 complete responders and 12 non-responders (gefitinib). All three responders harbored an EGFR mutation, none had a K-ras mutation. None of the non-responders had an EGFR mutation. Three of them had a K-ras mutation. In the prospective (enriched) series, 13 out of 41 patients (tumors) possessed an EGFR mutation. Eleven of them swiftly responded on erlotinib or gefitinib, 1 had stable disease, 1 stopped treatment due to severe toxicity. K-ras mutations were not found in this set. In a single EGFR mutation positive patient survival has extended over 40 months since start of therapy. Conclusions: Our findings corroborate other groups’ conclusions that EGFR mutations are a powerful indicator of response to TKI’s and that K-ras mutations are associated with resistance. [Table: see text]
Assessment of circulating tumor cells in breast cancer patients undergoing neoadjuvant chemotherapy
Authors: Smerage J. B. , Hayes D. F. , Doyle G. V. , Terstappen L. W. , Brown M. E. , Schott A. F. 
Published: March 2020

10079 Background: Circulating tumor cells (CTCs) are a valuable prognostic factor in metastatic breast cancer, suggesting that CTCs, if present, may be clinically useful in other breast cancer (BC) settings. This study prospectively evaluated CTCs before and after neoadjuvant chemotherapy (NACT) in patients with operable breast cancer. Methods: 7.5 or 30ml of blood were drawn in CellSave tubes from 26 Pts about to receive NACT (docetaxel + capecitabine followed by adriamycin + cytoxan) followed by surgery. CTC analysis is being performed at multiple time points. Data presented are from baseline (prior to first dose), post-NACT, and 3 months after surgery. CTCs were measured by immunomagnetic separation and automated fluorescent microscopy using the CellSearch System (Veridex/Immunicon Corp). Results: Baseline CTCs: For the first 11 pts CTCs were analyzed from 7.5ml of blood. 36% (4/11) had ≥1 CTC, 27% (3/11) had ≥2 CTCs. Of pts with detectable CTCs, the mean was 2.75 CTCs/7.5ml (range 1–4). To improve baseline sensitivity, 30ml blood was drawn from the subsequent 15 pts. One sample was not evaluable. 50% (7/14) had ≥1 detectable CTC and 29% (4/14) had ≥2 CTCs. Of pts with detectable CTCs, the mean was 3.0 CTCs/30ml (range 1–10). CTCs post-neoadjuvant therapy: All 26 pts had 30ml of blood drawn for CTC analysis. 27% (7/26) had ≥1 CTC, and 8% (2/26) had ≥2 CTCs. Using as threshold of ≥2 CTCs to define elevated, CTCs post-chemotherapy were compared to the pathologic complete response (pCR). Sensitivity was 10% (2 of 18 pts with residual disease had elevated CTCs). Specificity was 100% (0 of 7 pts with a pCR had elevated CTCs). This correlated to a positive predictive value of 100% and a negative predictive value (NPV) of 28%. CTCs 3 months after surgery: Of 21 pts analyzed, only one pt (5%) had a single CTC. Long-term follow-up blood collection is ongoing. Conclusions: CTCs are detectable in ∼30% locally advanced BC. All patients with CTCs after NACT had residual disease at surgery, and no CTCs were detected in patients with pCR. However, the absence of CTCs after NACT did not predict pCR. Pts will be followed to determine if CTCs correlate with recurrence and survival. [Table: see text]
Pretherapeutic circulating endostatin levels in patients with gastric cancer
Authors: Hong S. H. , Woo I. S. , Jeon H. M. , Rho S. Y. , Koh S. J. , Lee M. A. , Byun J. H. , Kang J. H. , Hong Y. S. , Lee K. S. 
Published: March 2020

10095 Background: Endostatin is an antiangiogenic fragment of collagen XVIII and is generated by tumor-derived proteases. The functional activity of circulating endostatin is currently unknown. This is the first report on serum endostatin in gastric cancer. Methods: A total of 111 patients with gastric cancer (52 metastatic patients and 59 patients undergoing gastrectomy without distant metastasis) were included in the study. Forty eight of 52 (92%) metastatic patients received systemic chemotherapy. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA and compared with the levels in 30 healthy controls. Data were analyzed using Student’s t-test and one-way ANOVA to compare means between groups, and using Spearman rank correlation to assess correlations between clinicopathologic factors and serum endostatin and VEGF levels. Survival curves were analyzed and compared using the Kaplan-Meier method and log-rank test. Results: Mean serum endostatin and VEGF levels were higher in gastric cancer patients than in healthy controls (endostatin, 69.8 ± 16.3 vs. 52.8 ± 6.0 ng/ml [P <0.001]; VEGF, 55.2 ± 7.5 vs. 31.9 ± 2.5 ng/ml [P <0.001]). Endostatin and VEGF levels were significantly higher in sera from metastatic patients than in sera from patients without distant metastasis (endostatin, 79.5 ± 17.9 vs. 61.3 ± 8.2 ng/ml [P <0.001]; VEGF, 57.4 ± 7.3 vs. 53.2 ± 7.2 ng/ml [P = 0.003]). There was a significant association between endostatin levels and the presence of distant metastases (r= 0.674; P <0.001). A correlation was also observed between serum endostatin and VEGF levels (r= 0.718; P <0.001). There was no significant difference in serum endostatin according to depth of tumor invasion, Lauren’s classification, differentiation, or regional lymph node status. A serum endostatin level higher than the median (78.14 ng/ml) was associated with a poor prognosis in metastatic gastric cancer (last follow- up at 42 months, median survival time 9 vs. 20 months [P=0.02]). Conclusions: In gastric cancer patients, serum endostatin levels are elevated and correlate with circulating VEGF levels as well as the presence of distant metastases. The endostatin level at diagnosis of metastatic gastric cancer may be useful for predicting survival time. No significant financial relationships to disclose.