bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower objectively and subjectively assessed numeracy are both associated with poorer self-rated health
Authors: Benda Natalie C. , Yang Zihan , Li Haojia , Zhang Tianran , Ancker Jessica S. 
Published: August 2021

Abstract
Objective
To compare an objective with a subjective numeracy assessment for association with self-reported health status, where numeracy refers to “the degree to which individuals have the capacity to access, process, interpret, communicate, and act on numerical, quantitative, graphical, biostatistical, and probabilistic health information needed to make effective health decisions”

Results
We completed a secondary analysis of two population-based surveys, the Empire State Poll (n = 763) and the Program for the International Assessment of Adult Competencies (PIAAC; n = 2609). The first survey assessed numeracy with a 3-item subjective instrument. The second assessed numeracy with more than 20 math problems. Both used the same measure for self-reported health status. Lower numeracy, whether subjectively or objectively assessed, was associated with worse self-reported health, even after controlling for education and other sociodemographic confounders. The odds ratios for the association were very similar (0.91 and 0.90 respectively). A lengthy objective numeracy assessment and a brief self-report assessment had similar associations with health status. A brief self-report measure of numeracy has similar properties to a lengthy objective assessment and is likely to be more feasible to use to screen patients in practice.
Identifying causal models between genetically regulated methylation patterns and gene expression in healthy colon tissue
Authors: Díez-Villanueva Anna , Jordà Mireia , Carreras-Torres Robert , Alonso Henar , Cordero David , Guinó Elisabet , Sanjuan Xavier , Santos Cristina , Salazar Ramón , Sanz-Pamplona Rebeca , Moreno Victor 
Published: August 2021

AbstractBackgroundDNA methylation is involved in the regulation of gene expression and phenotypic variation, but the inter-relationship between genetic variation, DNA methylation and gene expression remains poorly understood. Here we combine the analysis of genetic variants related to methylation markers (methylation quantitative trait loci: mQTLs) and gene expression (expression quantitative trait loci: eQTLs) with methylation markers related to gene expression (expression quantitative trait methylation: eQTMs), to provide novel insights into the genetic/epigenetic architecture of colocalizing molecular markers.ResultsNormal mucosa from 100 patients with colon cancer and 50 healthy donors included in the Colonomics project have been analyzed. Linear models have been used to find mQTLs and eQTMs within 1 Mb of the target gene. From 32,446 eQTLs previously detected, we found a total of 6850 SNPs, 114 CpGs and 52 genes interrelated, generating 13,987 significant combinations of co-occurring associations (meQTLs) after Bonferromi correction. Non-redundant meQTLs were 54, enriched in genes involved in metabolism of glucose and xenobiotics and immune system. SNPs in meQTLs were enriched in regulatory elements (enhancers and promoters) compared to random SNPs within 1 Mb of genes. Three colorectal cancer GWAS SNPs were related to methylation changes, and four SNPs were related to chemerin levels. Bayesian networks have been used to identify putative causal relationships among associated SNPs, CpG and gene expression triads. We identified that most of these combinations showed the canonical pathway of methylation markers causes gene expression variation (60.1%) or non-causal relationship between methylation and gene expression (33.9%); however, in up to 6% of these combinations, gene expression was causing variation in methylation markers.ConclusionsIn this study we provided a characterization of the regulation between genetic variants and inter-dependent methylation markers and gene expression in a set of 150 healthy colon tissue samples. This is an important finding for the understanding of molecular susceptibility on colon-related complex diseases.
DNA methylome profiling reveals epigenetic regulation of lipoprotein-associated phospholipase A2 in human vulnerable atherosclerotic plaque
Authors: Li Jingjin , Zhang Xiaoping , Yang Mengxi , Yang Hang , Xu Ning , Fan Xueqiang , Liu Gang , Jiang Xintong , Fan Jiasai , Zhang Lifang , Zhang Hu , Zhou Ying , Li Rui , Gao Si , Jin Jiangli , Jin Zening , Zheng Jingang , Tu Qiang , Ren Jingyi 
Published: August 2021

Abstract
Background
Atherosclerotic plaque vulnerability is a key feature of atheroprogression and precipitating acute cardiovascular events. Although the pivotal role of epigenetic regulation in atherosclerotic plaque destabilization is being recognized, the DNA methylation profile and its potential role in driving the progression and destabilization of atherosclerotic cardiovascular disease remains largely unknown. We conducted a genome-wide analysis to identify differentially methylated genes in vulnerable and non-vulnerable atherosclerotic lesions to understand more about pathogenesis.

Results
We compared genome-wide DNA methylation profiling between carotid artery plaques of patients with clinically symptomatic (recent stroke or transient ischemic attack) and asymptomatic disease (no recent stroke) using Infinium Methylation BeadChip arrays, which revealed 90,368 differentially methylated sites (FDR < 0.05, |delta beta|> 0.03) corresponding to 14,657 annotated genes. Among these genomic sites, 30% were located at the promoter regions and 14% in the CpG islands, according to genomic loci and genomic proximity to the CpG islands, respectively. Moreover, 67% displayed hypomethylation in symptomatic plaques, and the differentially hypomethylated genes were found to be involved in various aspects of inflammation. Subsequently, we focus on CpG islands and revealed 14,596 differentially methylated sites (|delta beta|> 0.1) located at the promoter regions of 7048 genes. Integrated analysis of methylation and gene expression profiles identified that 107 genes were hypomethylated in symptomatic plaques and showed elevated expression levels in both advanced plaques and ruptured plaques. The imprinted gene PLA2G7, which encodes lipoprotein-associated phospholipase A2 (Lp-PLA2), was one of the top hypomethylated genes with an increased expression upon inflammation. Further, the hypomethylated CpG site at the promoter region of PLA2G7 was identified as cg11874627, demethylation of which led to increased binding of Sp3 and expression of Lp-PLA2 through bisulfate sequencing, chromatin immunoprecipitation assay and enzyme-linked immunosorbent assay. These effects were further enhanced by deacetylase.

Conclusion
Extensive DNA methylation modifications serve as a new and critical layer of biological regulation that contributes to atheroprogression and destabilization via inflammatory processes. Revelation of this hitherto unknown epigenetic regulatory mechanism could rejuvenate the prospects of Lp-PLA2 as a therapeutic target to stabilize the atherosclerotic plaque and reduce clinical sequelae.
A preliminary study of synthetic magnetic resonance imaging in rectal cancer: imaging quality and preoperative assessment
Authors: Zhao Li , Liang Meng , Wu Pu-yeh , Yang Yang , Zhang Hongmei , Zhao Xinming 
Published: August 2021

Abstract
Purpose
To compare the imaging quality, T stage and extramural venous invasion (EMVI) evaluation between the conventional and synthetic T2-weighted imaging (T2WI), and to investigate the role of quantitative values obtained from synthetic magnetic resonance imaging (MRI) for assessing nodal staging in rectal cancer (RC).

Methods
Ninety-four patients with pathologically proven RC who underwent rectal MRI examinations including synthetic MRI were retrospectively recruited. The image quality of conventional and synthetic T2WI was compared regarding signal-to-noise ratio (SNR), contrast-to-noise (CNR), sharpness of the lesion edge, lesion conspicuity, absence of motion artifacts, and overall image quality. The accuracy of T stage and EMVI evaluation on conventional and synthetic T2WI were compared using the Mc-Nemar test. The quantitative T1, T2, and PD values were used to predict the nodal staging of MRI-evaluated node-negative RC.

Results
There were no statistically significant differences between conventional and synthetic T2WI in SNR, CNR, overall image quality, lesion conspicuity, and absence of motion artifacts (p = 0.058–0.978). There were no significant differences in the diagnostic accuracy of T stage and EMVI between conventional and synthetic T2WI from two observers (p = 0.375 and 0.625 for T stage; p = 0.625 and 0.219 for EMVI). The T2 value showed good diagnostic performance for predicting the nodal staging of RC with the area under the receiver operating characteristic, sensitivity, specificity, and accuracy of 0.854, 90.0%, 71.4%, and 80.3%, respectively.

Conclusions
Synthetic MRI may facilitate preoperative staging and EMVI evaluation of RC by providing synthetic T2WI and quantitative maps in one acquisition.
Preselection of robust radiomic features does not improve outcome modelling in non-small cell lung cancer based on clinical routine FDG-PET imaging
Authors: Oliveira Carol , Amstutz Florian , Vuong Diem , Bogowicz Marta , Hüllner Martin , Foerster Robert , Basler Lucas , Schröder Christina , Eboulet Eric I. , Pless Miklos , Thierstein Sandra , Peters Solange , Hillinger Sven , Tanadini-Lang Stephanie , Guckenberger Matthias 
Published: August 2021

Abstract
Background
Radiomics is a promising tool for identifying imaging-based biomarkers. Radiomics-based models are often trained on single-institution datasets; however, multi-centre imaging datasets are preferred for external generalizability owing to the influence of inter-institutional scanning differences and acquisition settings. The study aim was to determine the value of preselection of robust radiomic features in routine clinical positron emission tomography (PET) images to predict clinical outcomes in locally advanced non-small cell lung cancer (NSCLC).

Methods
A total of 1404 primary tumour radiomic features were extracted from pre-treatment [18F]fluorodeoxyglucose (FDG)-PET scans of stage IIIA/N2 or IIIB NSCLC patients using a training cohort (n = 79; prospective Swiss multi-centre randomized phase III trial SAKK 16/00; 16 centres) and an internal validation cohort (n = 31; single centre). Robustness studies investigating delineation variation, attenuation correction and motion were performed (intraclass correlation coefficient threshold > 0.9). Two 12-/24-month event-free survival (EFS) and overall survival (OS) logistic regression models were trained using standardized imaging: (1) with robust features alone and (2) with all available features. Models were then validated using fivefold cross-validation, and validation on a separate single-centre dataset. Model performance was assessed using area under the receiver operating characteristic curve (AUC).

Results
Robustness studies identified 179 stable features (13%), with 25% stable features for 3D versus 4D acquisition, 31% for attenuation correction and 78% for delineation. Univariable analysis found no significant robust features predicting 12-/24-month EFS and 12-month OS (p value > 0.076). Prognostic models without robust preselection performed well for 12-month EFS in training (AUC = 0.73) and validation (AUC = 0.74). Patient stratification into two risk groups based on 12-month EFS was significant for training (p value = 0.02) and validation cohorts (p value = 0.03).

Conclusions
A PET-based radiomics model using a standardized, multi-centre dataset to predict EFS in locally advanced NSCLC was successfully established and validated with good performance. Prediction models with robust feature preselection were unsuccessful, indicating the need for a standardized imaging protocol.
PSMA-ligand uptake can serve as a novel biomarker in primary prostate cancer to predict outcome after radical prostatectomy
Authors: Wang Hui , Amiel Thomas , Würnschimmel Christoph , Langbein Thomas , Steiger Katja , Rauscher Isabel , Horn Thomas , Maurer Tobias , Weber Wolfgang , Wester Hans-Juergen , Knorr Karina , Eiber Matthias 
Published: August 2021

Abstract
Background
The prostate-specific membrane antigen (PSMA) is a relevant target in prostate cancer, and immunohistochemistry studies showed associations with outcome. PSMA-ligand positron emission tomography (PET) is increasingly used for primary prostate cancer staging, and the molecular imaging TNM classification (miTNM) standardizes its reporting. We aimed to investigate the potential of PET-imaging to serve as a noninvasive imaging biomarker to predict disease outcome in primary prostate cancer after radical prostatectomy (RP).

Methods
In this retrospective analysis, 186 primary prostate cancer patients treated with RP who had undergone a 68Ga-PSMA-11 PET up to three months prior to the surgery were included. Maximum standardized uptake value (SUVmax), SUVmean, tumor volume (TV) and total lesion (TL) were collected from PET-imaging. Moreover, clinicopathological information, including age, serum prostate-specific antigen (PSA) level, and pathological characteristics, was assessed for disease outcome prediction. A stage group system for PET-imaging findings based on the miTNM framework was developed.

Results
At a median follow-up after RP of 38 months (interquartile range (IQR) 22–53), biochemical recurrence (BCR) was observed in 58 patients during the follow-up period. A significant association between a positive surgical margin and miN status (miN1 vs. miN0, odds ratio (OR): 5.428, p = 0.004) was detected. miT status (miT ≥ 3a vs. miT < 3, OR: 2.696, p = 0.003) was identified as an independent predictor for Gleason score (GS) ≥ 8. Multivariate Cox regression analysis indicated that PSA level (hazard ratio (HR): 1.024, p = 0.014), advanced GS (GS ≥ 8 vs. GS < 8, HR: 3.253, p < 0.001) and miT status (miT ≥ 3a vs. miT < 3, HR: 1.941, p = 0.035) were independent predictors for BCR. For stage I disease as determined by PET-imaging, a shorter BCR-free survival was observed in the patients with higher SUVmax (IA vs. IB stage, log-rank, p = 0.022).

Conclusion
Preoperative miTNM classification from 68Ga-PSMA-11 PET correlates with postoperative GS, surgical margin status and time to BCR. The association between miTNM staging and outcome proposes 68Ga-PSMA-11 PET as a novel non-invasive imaging biomarker and potentially serves for ancillary pre-treatment stratification.
Investigation of spleen CXCR4 expression by [68Ga]Pentixafor PET in a cohort of 145 solid cancer patients
Authors: Lewis Richard , Habringer Stefan , Kircher Malte , Hefter Maike , Peuker Caroline Anna , Werner Rudolf , Ademaj-Kospiri Valëza , Gäble Alexander , Weber Wolfgang , Wester Hans-Jürgen , Buck Andreas , Herhaus Peter , Lapa Constantin , Keller Ulrich 
Published: August 2021

Abstract
Background
The chemokine receptor CXCR4 is frequently overexpressed and associated with adverse prognosis in most hematopoietic malignancies and solid cancers. Recently, CXCR4 molecular imaging using the CXCR4-specific positron emission tomography (PET) tracer Pentixafor ([68Ga]Pentixafor) has become a well-established method to non-invasively measure CXCR4 expression in vivo. In previous Pentixafor imaging studies, highly variable CXCR4 tracer uptake to the spleen was observed.

Results
We investigated the hypothesis that enhanced spleen [68Ga]Pentixafor uptake and thus CXCR4 expression in patients with solid tumors would indicate an activated spleen state and/or an association with clinical and prognostic features and survival parameters. In this retrospective study, [68Ga]Pentixafor-PET images and patient records of 145 solid tumor patients representing 27 cancer entities were investigated for an association of spleen [68Ga]Pentixafor uptake and clinical characteristics and outcome. Based on this assessment, we did not observe differences in clinical outcomes, measured by progression-free survival, overall survival and remission status neither within the entire cohort nor within subgroups of adrenal cancer, desmoplastic small round cell tumor, neuroendocrine tumors, non-small cell lung cancer, small cell lung cancer and pancreatic adenocarcinoma patients. No tumor entity showed especially high levels of spleen [68Ga]Pentixafor uptake compared to others or a control cohort. However, when investigating laboratory parameters, there was a positive correlation of high spleen [68Ga]Pentixafor uptake with leukocyte and/or platelet counts in neuroendocrine tumors, non-small cell lung cancer and small cell lung cancer.

Conclusion
Spleen [68Ga]Pentixafor uptake was not associated with stage of disease and clinical outcomes in solid tumor patients. We identified positively associated platelet and/or leukocyte counts with spleen [68Ga]Pentixafor uptake in neuroendocrine tumors, non-small cell lung cancer and small cell lung cancer, suggesting that splenic CXCR4 expression could possibly play a role in systemic immunity/inflammation in some types of solid tumors or a subgroup of patients within solid tumor entities.
[18F]FDG-PET/CT in prone compared to supine position for optimal axillary staging and treatment in clinically node-positive breast cancer patients with neoadjuvant systemic therapy
Authors: van Loevezijn Ariane A. , Stokkel Marcel P. M. , Donswijk Maarten L. , van Werkhoven Erik D. , van der Noordaa Marieke E. M. , van Duijnhoven Frederieke H. , Vrancken Peeters Marie-Jeanne T. F. D. 
Published: August 2021

Abstract
Purpose
Axillary staging before neoadjuvant systemic therapy in clinically node-positive breast cancer patients with tailored axillary treatment according to the Marking Axillary lymph nodes with radioactive iodine seeds (MARI)-protocol, a protocol developed at the Netherlands Cancer Institute, is performed with [18F] fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT). We aimed to assess the value of FDG-PET/CT in prone compared to standard supine position for axillary staging.

Methods
We selected patients with FDG-PET/CT in supine and prone position who underwent the MARI-protocol. One hour after administration of 3.5 MBq/kg, [18F]FDG-PET was performed with a low-dose prone position CT-thorax followed by a supine whole-body scan. Scans were separately reviewed by two nuclear medicine physicians and categorized by number of FDG-positive axillary lymph nodes (ALNs; cALN<4 or cALN≥4). Main outcome was axillary up- or downstaging.

Results
Of 153 patients included, 24 (16%) patients were up- or downstaged at evaluation of prone images: One observer upstaged 14 patients, downstaged 3 patients and reported a higher number of ALNs (3.6 vs. 3.2, p < 0.001), while staging (4 up- and 5 downstaged) and number of ALNs (2.8 vs. 2.8) did not differ for the other. Observers agreed on up- or downstaging in only 1 (1%) patient. Irrespective of supine or prone position scanning, observers agreed on axillary staging in 124 (81%) patients and disagreed in 5 (3%). Interobserver agreement was lower with prone assessments (86%, K = 0.67) than supine (92%, K = 0.80).

Conclusions
Axillary staging with FDG-PET/CT in prone compared to supine position did not result in concordant up- or downstaging. Therefore, FDG-PET/CT in supine position only can be considered sufficient for axillary staging.
On some new midpoint inequalities for the functions of two variables via quantum calculus
Authors: You Xuexiao , Ali Muhammad Aamir , Erden Samet , Budak Hüseyin , Chu Yu-Ming 
Published: August 2021

AbstractIn this paper, first we obtain a new identity for quantum integrals, the result is then used to prove midpoint type inequalities for differentiable coordinated convex mappings. The outcomes provided in this article are an extension of the comparable consequences in the literature on the midpoint inequalities for differentiable coordinated convex mappings.
Modeling, analysis and numerical solution to malaria fractional model with temporary immunity and relapse
Authors: ul Rehman Attiq , Singh Ram , Abdeljawad Thabet , Okyere Eric , Guran Liliana 
Published: August 2021

AbstractThe present paper deals with a fractional-order mathematical epidemic model of malaria transmission accompanied by temporary immunity and relapse. The model is revised by using Caputo fractional operator for the index of memory. We also recommend the utilization of temporary immunity and the possibility of relapse. The theory of locally bounded and Lipschitz is employed to inspect the existence and uniqueness of the solution of the malaria model. It is shown that temporary immunity has a great effect on the dynamical transmission of host and vector populations. The stability analysis of these equilibrium points for fractional-order derivative α and basic reproduction number $\mathcal{R}_{0}$

R
0

is discussed. The model will exhibit a Hopf-type bifurcation. The two control variables are introduced in this model to decrease the number of populations. Mandatory conditions for the control problem are produced. Two types of numerical method via Laplace Adomian decomposition and Runge–Kutta of fourth order for simulating the proposed model with fractional-order derivative are presented. To validate the mathematical results, numerical simulations, sensitivity analysis, convergence analysis, and other important studies are given. The paper is finished with some conclusions and discussion.
Refinements of some fractional integral inequalities for refined $(\alpha ,h-m)$-convex function
Authors: Jung Chahn Yong , Farid Ghulam , Yasmeen Hafsa , Lv Yu-Pei , Pečarić Josip 
Published: August 2021

AbstractThis article investigates new inequalities for generalized Riemann–Liouville fractional integrals via the refined $(\alpha ,h-m)$
(
α
,
h
−
m
)
-convex function. The established results give refinements of fractional integral inequalities for $(h-m)$
(
h
−
m
)
-convex, $(\alpha ,m)$
(
α
,
m
)
-convex, $(s,m)$
(
s
,
m
)
-convex, and related functions. Also, the k-fractional versions of given inequalities by using a parameter substitution are provided.
Severity: a QoS-aware approach to cloud application elasticity
Authors: Tsagkaropoulos Andreas , Verginadis Yiannis , Papageorgiou Nikos , Paraskevopoulos Fotis , Apostolou Dimitris , Mentzas Gregoris 
Published: August 2021

AbstractWhile a multitude of cloud vendors exist today offering flexible application hosting services, the application adaptation capabilities provided in terms of autoscaling are rather limited. In most cases, a static adaptation action is used having a fixed scaling response. In the cases that a dynamic adaptation action is provided, this is based on a single scaling variable. We propose Severity, a novel algorithmic approach aiding the adaptation of cloud applications. Based on the input of the DevOps, our approach detects situations, calculates their Severity and proposes adaptations which can lead to better application performance. Severity can be calculated for any number of application QoS attributes and any type of such attributes, whether bounded or unbounded. Evaluation with four distinct workload types and a variety of monitoring attributes shows that QoS for particular application categories is improved. The feasibility of our approach is demonstrated with a prototype implementation of an application adaptation manager, for which the source code is provided.