bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Fusion Burden as a Hallmark of Immune Infiltration in Prostate Cancer
Authors: Wagle Marie-Claire , Castillo Joseph , Srinivasan Shrividhya , Holcomb Thomas , Yuen Kobe C. , Kadel Edward E. , Mariathasan Sanjeev , Halligan Daniel L. , Carr Adrian R. , Bylesjo Max , McAdam Paul R. , Lynagh Sarah , Marien Koen M. , Kockx Mark , Waumans Yannick , Huang Shih-Min A. , Lackner Mark R. , Mounir Zineb 
Published: April 2020

AbstractProstate cancer is the second leading cause of cancer-related death in men. Despite having a relatively lower tumor mutational burden than most tumor types, multiple gene fusions such as TMPRSS2:ERG have been characterized and linked to more aggressive disease. Individual tumor samples have been found to contain multiple fusions, and it remains unknown whether these fusions increase tumor immunogenicity. Here, we investigated the role of fusion burden on the prevalence and expression of key molecular and immune effectors in prostate cancer tissue specimens that represented the different stages of disease progression and androgen sensitivity, including hormone-sensitive and castration-resistant prostate cancer. We found that tumor fusion burden was inversely correlated with tumor mutational burden and not associated with disease stage. High fusion burden correlated with high immune infiltration, PD-L1 expression on immune cells, and immune signatures, representing activation of T cells and M1 macrophages. High fusion burden inversely correlated with immune-suppressive signatures. Our findings suggest that high tumor fusion burden may be a more appropriate biomarker than tumor mutational burden in prostate cancer, as it more closely associates with immunogenicity, and suggests that tumors with high fusion burden could be potential candidates for immunotherapeutic agents.
Recovery of Absolute Coronary Blood Flow and Microvascular Resistance After Chronic Total Occlusion Percutaneous Coronary Intervention: An Exploratory Study
Authors: Keulards Daniëlle C. J. , Karamasis Grigoris V. , Alsanjari Osama , Demandt Jesse P. A. , van't Veer Marcel , Zelis Jo M. , Dello Simon A. , El Farissi Mohamed , Konstantinou Klio , Tang Kare H. , Kelly Paul A. , Keeble Thomas R. , Pijls Nico H. J. , Davies John R. , Teeuwen Koen 
Published: April 2020

Background

This study aimed to investigate longitudinal physiological changes in the recanalized coronary chronic total occlusion (CTO) vessel and its dependent myocardium after successful percutaneous coronary intervention (
PCI
).

Methods and Results

In this pilot study, 25 patients scheduled for elective
CTO PCI
with viable myocardium and angiographically visible collaterals were included. Absolute coronary blood flow and absolute microvascular resistance were measured invasively using continuous thermodilution. Measurements were performed immediately after successful
CTO PCI
and at short‐term follow‐up. In a subgroup of patients, physiological measurements were performed at the predominant donor vessel before
CTO PCI
, immediately afterwards, and at follow‐up. Absolute coronary blood flow in the recanalized
CTO
artery increased from 148±53
mL
/min immediately after
PCI
to 221±77
mL
/min at follow‐up (
P
<0.001). In agreement, absolute resistance in the myocardial territory perfused by the
CTO
artery, decreased from 545±255 Wood units immediately after the procedure to 387±128 Wood units at follow‐up (
P
=0.014). There were no significant changes in the absolute coronary blood flow and resistance in the predominant donor between baseline and follow‐up. Positive remodeling of the distal
CTO
vessel with an increase in lumen diameter was observed.

Conclusions

After successful
CTO PCI
, blood flow in the recanalized artery and microvascular function of the dependent myocardium are not immediately normal but recover over time.
Gaps in Dyslipidemia Care Among Working‐Aged Individuals With Employer‐Sponsored Health Care
Authors: Shiffman Dov , Louie Judy Z. , Devlin James J. , Knowles Joshua W. , McPhaul Michael J. 
Published: April 2020

Background
The American Heart Association and American College of Cardiology guidelines defined patient‐management groups that would benefit from lowering of low‐density lipoprotein cholesterol (LDL‐C). We assessed gaps in dyslipidemia care among employees and spouses with health benefits.

Methods and Results

We studied 17 889 employees and spouses who were covered by an employer‐sponsored health plan and participated in an annual health assessment. Using medical claims, laboratory tests, and risk assessment questionnaires, we found that 43% of participants were in one of 4 patient‐management groups: secondary prevention, severe hypercholesterolemia (
LDL
‐C ≥190 mg/dL at least once in the preceding 5 years), diabetes mellitus, or elevated 10‐year risk of cardiovascular disease. To assess gaps in dyslipidemia care, we used
LDL
‐C ≤70 mg/dL as the goal for both the secondary prevention group and those in the elevated 10‐year risk group with >20% risk; LDL‐C ≤100 mg/dL was used for the other groups. Among those in patient‐management groups, 27.3% were in the secondary prevention group, 7.4% were in the severe hypercholesterolemia group, 29.9% were in the diabetes mellitus group, and 35.4% were in the elevated 10‐year risk group. About 74% of those in patient‐management groups had above‐goal
LDL
‐C levels, whereas only 31% had evidence of a lipid‐lowering therapy in the past 6 months: 45% in the secondary prevention group, 31% in the severe hypercholesterolemia group, 36% in the diabetes mellitus group, and 17% in the elevated 10‐year risk group.

Conclusions

The substantial gaps in
LDL
‐C treatment and goal attainment among members of an employer‐sponsored medical plan who were mostly aware of their
LDL
‐C levels indicate the need for gap‐closure initiatives.
Spatial Attention and Temporal Expectation Exert Differential Effects on Visual and Auditory Discrimination
Authors: Wilsch Anna , Mercier Manuel R. , Obleser Jonas , Schroeder Charles E. , Haegens Saskia 
Published: April 2020

Abstract
Anticipation of an impending stimulus shapes the state of the sensory systems, optimizing neural and behavioral responses. Here, we studied the role of brain oscillations in mediating spatial and temporal anticipations. Because spatial attention and temporal expectation are often associated with visual and auditory processing, respectively, we directly contrasted the visual and auditory modalities and asked whether these anticipatory mechanisms are similar in both domains. We recorded the magnetoencephalogram in healthy human participants performing an auditory and visual target discrimination task, in which cross-modal cues provided both temporal and spatial information with regard to upcoming stimulus presentation. Motivated by prior findings, we were specifically interested in delta (1–3 Hz) and alpha (8–13 Hz) band oscillatory state in anticipation of target presentation and their impact on task performance. Our findings support the view that spatial attention has a stronger effect in the visual domain, whereas temporal expectation effects are more prominent in the auditory domain. For the spatial attention manipulation, we found a typical pattern of alpha lateralization in the visual system, which correlated with response speed. Providing a rhythmic temporal cue led to increased postcue synchronization of low-frequency rhythms, although this effect was more broadband in nature, suggesting a general phase reset rather than frequency-specific neural entrainment. In addition, we observed delta-band synchronization with a frontal topography, which correlated with performance, especially in the auditory task. Combined, these findings suggest that spatial and temporal anticipations operate via a top–down modulation of the power and phase of low-frequency oscillations, respectively.
Disintegration as an Integrative Process: Revisiting Palestinian Cohesiveness from the Late Ottoman Era through the End of the British Mandate
Authors: Chorev Harel 
Published: April 2020

Abstract
The common narrative regarding the Palestinian Arabs during the British Mandate period highlights the disastrous effects of social and political disintegration on their integration as a national community, as well as on their ability to deal with the British and the Jewish Yishuv. The analysis offered here examines integration and disintegration processes in Palestinian society through diverse local, regional and national networks. The main argument is that disintegration and integration processes were not exclusively contradictory, as is commonly perceived, but rather dialectical developments that often ultimately served Palestinian integration, although this process did not mature until the fateful War of 1948.
Turkmen Literacy and Turkmen Identity before the Soviets: the Ravnaq al-Islām in Its Literary and Social Context
Authors: Frank Allen J. 
Published: April 2020

Abstract
Despite assertions of almost universal illiteracy among pre-Revolutionary Turkmens, an examination of the widely popular maktab primer, the Ravnaq al-Islām, shows that literacy among Turkmens before 1917 was substantially higher than previously thought. Additionally, the work and legends surrounding it show us Turkmen maktab texts contributed to a sense of supra-tribal Turkmen identity, which has generally been discounted or ignored in previous studies of Turkmen social history.
El Niño and the Nomads: Global Climate, Local Environment, and the Crisis of Pastoralism in Late Ottoman Kurdistan
Authors: Pehlivan Zozan 
Published: April 2020

Abstract
This article explores the impacts of environmental crises on pastoral nomads in Ottoman Kurdistan/Armenia in the late nineteenth-century. It demonstrates that the climatic fluctuations characterizing these environmental crises were synchronized with global climatic oscillations, specifically the El Niño Southern Oscillation. Recurrent episodes of severe drought and cold dramatically affected these groups, who were unable to withstand extreme changes in temperature and precipitation. Back-to-back drought episodes created a shortage of water, dried up pastures and damaged forage, while severe cold resulted in high rates of premature death among herd animals. These climatic events thus had devastating economic and social consequences.
Relating North American Indigenous History and the Study of Religion: Introducing a Review Symposium on Jennifer Graber’s The Gods of Indian Country and Pamela Klassen’s The Story of Radio Mind
Authors: Hermann Adrian 
Published: April 2020

Abstract
This article introduces a combined review symposium on Jennifer Graber’s The Gods of Indian Country: Religion and the Struggle for the American West (Oxford University Press, 2018) and Pamela Klassen’s The Story of Radio Mind: A Missionary’s Journey on Indigenous Land (University of Chicago Press, 2018). It presents the four contributions to the review symposium as well as Graber and Klassen’s response and relates the discussion of the book to broader questions of studying North American Indigenous history as a central part of the study of religion.
Introducing ‘Health Vulnerability’. Towards a Human Right Claim for Innovative Orphan Drugs?
Authors: Gennet Éloïse 
Published: April 2020

Abstract
Although several European law instruments specifically promote the development of orphan medicines, rare disease patients still suffer from an excessive lack of access to orphan drugs. In order to base a claim for equity of access to research benefits, health vulnerability is introduced as a human rights-based public health concept. It represents a potentially valuable and powerful means in European law for rare disease patients to claim for an improved public action to develop innovative orphan drugs, including through the use of novel data-driven technologies such as computer modelling and simulation, as they have the potential to palliate some of the obstacles in the current development process of orphan medicines. The human rights-based approach would be all the more valuable, as it would simultaneously draw attention on privacy aspects of vulnerability for orphan disease patients, especially regarding increased risks stemming from the processing of highly sensitive health data.
Improvement of Accuracy of Global Numerical Weather Prediction Using Refined Error Covariance Matrices
Authors: Ishibashi Toshiyuki 
Published: April 2020

Abstract
In data assimilation for NWP, accurate estimation of error covariance matrices (ECMs) and their use are essential to improve NWP accuracy. The objective of this study is to estimate ECMs of all observations and background variables using sampling statistics, and improve global NWP accuracy by using them. This study presents the first results of such all ECM refinement. ECM diagnostics combining multiple methods, and analysis and forecast cycle experiments were performed on the JMA global NWP system, where diagonal components of all ECMs and off-diagonal components of radiance observations are refined. The ECM diagnostic results are as follows: 1) the diagnosed error standard deviations (SDs) are generally much smaller than those of the JMA operational system (CNTL); 2) interchannel correlations in humidity-sensitive radiance errors are much larger than 0.2; and 3) horizontal correlation distances of AMSU-A are ~50 km, excluding channel 4. The experimental results include the following: 1) the diagnosed ECMs generally improve forecast accuracy over CNTL even without additional tunings; 2) the supplemental tuning parameter, which is the deflation factor (0.6 in SD) applied for the estimated ECMs of nonsatellite conventional data and GPS radio occultation data, statistically significantly improves forecast accuracy; 3) this value 0.6 is set as the same value as the ratio of the estimated background error SD to that in CNTL; 4) high-density assimilation (10 times) of AMSU-A is better than CNTL, not better than that with 5 times; and 5) ECMs estimated using boreal summer data can improve forecast accuracy in winter, which indicates their robustness.
The Effect of Endoscopic Sinus Surgery on Eustachian Tube Dysfunction Symptoms
Authors: Chang Michael T. , Hosseini Davood K. , Song Sun Hee , Nayak Jayakar V. , Patel Zara M. , Lee Jennifer Y. , Hwang Peter H. 
Published: April 2020

ObjectiveWe assessed how eustachian tube dysfunction (ETD) changed with endoscopic sinus surgery (ESS) and identified factors associated with improvement.Study DesignRetrospective chart review.SettingAcademic center.Subjects and MethodsPatients undergoing ESS for chronic rhinosinusitis with and without nasal polyposis (CRSwNP, CRSsNP) or recurrent acute rhinosinusitis (RARS) completed the Eustachian Tube Dysfunction Questionnaire 7 (ETDQ‐7) preoperatively and postoperatively at 2 weeks, 6 weeks, 3 months, and 6 months. Included in analyses were demographics, comorbidities, Sinonasal Outcome Test 22 (SNOT‐22), radiographic score, endoscopy score, procedure, and medication use. Regression analysis identified factors associated with improvement, defined as ΔETDQ‐7 >3.5.ResultsIn total, 302 patients were studied. ETD prevalence was 68% in CRSsNP, 48% in CRSwNP, and 88% in RARS. Patients with ETD had a mean baseline ETDQ‐7 of 25.8 ± 8.0 and improved postoperatively at 2 weeks (19.9 ± 8.1, P <. 001), 6 weeks (17.8 ± 9.3, P <. 001), 3 months (16.8 ± 8.5, P <. 001), and 6 months (16.4 ± 7.9, P <. 001). At 6 months, ETD improved in 89% of patients with CRSsNP, 68% with CRSwNP, and 78% with RARS. On multivariate analysis, ETD improvement was associated with higher preoperative ETDQ‐7 score (adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 1.04‐1.22; P =. 030), higher preoperative SNOT‐22 score (aOR, 1.02; 95% CI, 1.02‐1.08; P =. 001), higher preoperative SNOT‐22 ear subscore (aOR, 1.27; 95% CI, 1.02‐1.65; P =. 034), posterior ethmoidectomy (aOR, 1.59; 95% CI, 1.22‐4.92; P =. 025), and postoperative corticosteroid spray use (aOR, 1.57; 95% CI, 1.17‐1.66; P =. 008).ConclusionETD symptoms often improve following ESS. Factors associated with improvement include higher preoperative disease burden, posterior ethmoidectomy, and postoperative corticosteroid spray.Level of Evidence:4
Changes in mortality hazard of the Korean long-term dialysis population: The dependencies of time and modality switch
Authors: Jeong Jong Cheol , Kim Sejoong , Kim Ki Pyo , Yi Yongjin , Ahn Shin Young , Jin Dong-Chan , Chin Ho Jun , Chae Dong-Wan , Na Ki Young 
Published: April 2020

Background: Many studies have compared patient survival outcome between hemodialysis (HD) and peritoneal dialysis (PD); however, time-varying risks of dialysis modality have been rarely investigated. This study aimed to investigate dialysis modality switch and its association with the survival outcome in the Korean population. Methods: Data from the Korean Society of Nephrology were used. A total of 21,840 incident dialysis patients who started dialysis in or after 2000 were analyzed. For the survival analysis, both proportional and non-proportional hazard assumptions were applied. For the modality switch, time-varying covariate Cox regression was applied. Results: During the median follow-up of 8 years, PD group showed increased adjusted hazard ratio (HR) of 1.248 (95% CI 1.071–1.454, p = 0.004) for mortality. Interaction of PD status with female sex was significant with an HR of 1.080 (95% CI 1.000–1.165, p = 0.050). Dialysis modality switch was associated with increased HR of 1.094 (95% CI 1.015–1.180, p = 0.019), albeit switch from PD to HD did not show significant HR until 6 years. Interestingly, time-varying risk analysis showed a decreased HR of PD after 10 years in the non-switcher group, which was consistent in patients with high traditional risk factors (with diabetes, elderly). Conclusions: PD was associated with increased HR of mortality in the first 8 years, then it was associated with decreased HR of mortality after 10 years. Dialysis modality switch was associated with increased mortality risk, but switch from PD to HD within 6 years did not show significant hazard of mortality.
Dialectical Observation of Controllable Electrodeposited Ni Nanocones: the Unification of Local Disorder and Overall Order
Authors: Zou Ruiqing , Xiang Saidi , Wang Jian , Li Yuhe , Gu Lin , Wang Yanyan 
Published: April 2020

AbstractDense and ordered Ni nanocones with regular spiral textures had been successfully synthesized via a simple and inexpensive electrodeposition process in the solution containing sodium chloride (NaCl), nickel chloride hexahydrate (NiCl2·6H2O), and boric acid (H3BO3). After analyzing the microstructure, a more optimized possible growth mechanism of Ni nanocones was proposed, in which the growth process was divided into local and global aspects, named multi-dimensional growth mechanism of global order and local disorder. In an area small enough, any subtle state changes would cause disorder of Ni atom arrangement, which made the local microstructure appear disordered, but from a macro perspective, the difference between two adjacent disorders caused by different statuses was too small to be well reflected, only when the difference in state was large enough can the change be observed in the macroscopic appearance, so the global was orderly. Meanwhile, we found that the microstructure of Ni nanocones would be controlled in the electrodeposition solution by adjusting the experiment parameters such as the concentration of NaCl, NiCl2·6H2O, and H3BO3, which indirectly determined the microstructure in a large extent via controlling the generation of intermediate products and the pH.
Assessing the power of principal components and wright’s fixation index analyzes applied to reveal the genome-wide genetic differences between herds of Holstein cows
Authors: Smaragdov M. G. , Kudinov A. A. 
Published: April 2020

Abstract
Background
Due to the advent of SNP array technology, a genome-wide analysis of genetic differences between populations and breeds has become possible at a previously unattainable level. The Wright’s fixation index (Fst) and the principal component analysis (PCA) are widely used methods in animal genetics studies. In paper we compared the power of these methods, their complementing each other and which of them is the most powerful.

Results
Comparative analysis of the power Principal Components Analysis (PCA) and Fst were carried out to reveal genetic differences between herds of Holsteinized cows. Totally, 803 BovineSNP50 genotypes of cows from 13 herds were used in current study. Obtained Fst values were in the range of 0.002–0.012 (mean 0.0049) while for rare SNPs with MAF 0.0001–0.005 they were even smaller in the range of 0.001–0.01 (mean 0.0027). Genetic relatedness of the cows in the herds was the cause of such small Fst values. The contribution of rare alleles with MAF 0.0001–0.01 to the Fst values was much less than common alleles and this effect depends on linkage disequilibrium (LD). Despite of substantial change in the MAF spectrum and the number of SNPs we observed small effect size of LD - based pruning on Fst data. PCA analysis confirmed the mutual admixture and small genetic difference between herds. Moreover, PCA analysis of the herds based on the visualization the results of a single eigenvector cannot be used to significantly differentiate herds. Only summed eigenvectors should be used to realize full power of PCA to differentiate small between herds genetic difference. Finally, we presented evidences that the significance of Fst data far exceeds the significance of PCA data when these methods are used to reveal genetic differences between herds.

Conclusions
LD - based pruning had a small effect on findings of Fst and PCA analyzes. Therefore, for weakly structured populations the LD - based pruning is not effective. In addition, our results show that the significance of genetic differences between herds obtained by Fst analysis exceeds the values of PCA. Proposed, to differentiate herds or low structured populations we recommend primarily using the Fst approach and only then PCA.