bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CpG Methylation Classifier to Predict Relapse in Adults with T-Cell Lymphoblastic Lymphoma
Authors: Tian Xiao-Peng , Su Ning , Wang Liang , Huang Wei-Juan , Liu Yan-Hui , Zhang Xi , Huang Hui-Qiang , Lin Tong-Yu , Ma Shu-Yun , Rao Hui-Lan , Li Mei , Liu Fang , Zhang Fen , Zhong Li-Ye , Liang Li , Lan Xiao-Liang , Li Juan , Liao Bing , Li Zhi-Hua , Tang Qiong-Lan , Liang Qiong , Shao Chun-Kui , Zhai Qiong-Li , Cheng Run-Fen , Sun Qi , Ru Kun , Gu Xia , Lin Xi-Na , Yi Kun , Shuang Yue-Rong , Chen Xiao-Dong , Dong Wei , Sun Cai , Sang Wei , Liu Hui , Zhu Zhi-Gang , Rao Jun , Guo Qiao-Nan , Zhou Ying , Meng Xiang-Ling , Zhu Yong , Hu Chang-Lu , Jiang Yi-Rong , Zhang Ying , Gao Hong-Yi , He Wen-Jun , Xia Zhong-Jun , Pan Xue-Yi , Hai Lan , Li Guo-Wei , Song Li-Yan , Kang Tie-Bang , Xie Dan , Cai Qing-Qing 
Published: March 2020

AbstractPurpose:Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens.Experimental Design:A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine–recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321).Results:The four-CpG–based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P &lt; 0.001). This classifier also showed good predictive value in the internal testing cohort (P &lt; 0.001) and the independent validation cohort (P &lt; 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation.Conclusions:Our four-CpG–based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.
Honing in on PARPi Response in Prostate Cancer: from HR Pathway to Gene-by-Gene Granularity
Authors: Sokolova Alexandra O. , Yu Evan Y. , Cheng Heather H. 
Published: March 2020

Abstract
PARP inhibitors (PARPi) are promising in BRCA2-altered prostate cancer. Data were presented on PARPi efficacy in prostate cancers with alterations in other DNA damage repair genes which suggest low response rates in ATM-, CHEK2-, CDK12-altered tumors and promising results in PALB2-, RAD51B-, FANCA-, and BRIP1-altered tumors.
See related article by Abida et al., p. 2487
Growth-Inhibitory Activity of Bone Morphogenetic Protein 4 in Human Glioblastoma Cell Lines Is Heterogeneous and Dependent on Reduced SOX2 Expression
Authors: Dalmo Erika , Johansson Patrik , Niklasson Mia , Gustavsson Ida , Nelander Sven , Westermark Bengt 
Published: March 2020

Abstract

Glioblastoma multiforme continues to have a dismal prognosis. Even though detailed information on the genetic aberrations in cell signaling and cell-cycle checkpoint control is available, no effective targeted treatment has been developed. Despite the advanced molecular defects, glioblastoma cells may have remnants of normal growth-inhibitory pathways, such as the bone morphogenetic protein (BMP) signaling pathway. We have evaluated the growth-inhibitory effect of BMP4 across a broad spectrum of patient samples, using a panel of 40 human glioblastoma initiating cell (GIC) cultures. A wide range of responsiveness was observed. BMP4 sensitivity was positively correlated with a proneural mRNA expression profile, high SOX2 activity, and BMP4-dependent upregulation of genes associated with inhibition of the MAPK pathway, as demonstrated by gene set enrichment analysis. BMP4 response in sensitive cells was mediated by the canonical BMP receptor pathway involving SMAD1/5/9 phosphorylation and SMAD4 expression. SOX2 was consistently downregulated in BMP4-treated cells. Forced expression of SOX2 attenuated the BMP4 sensitivity including a reduced upregulation of MAPK-inhibitory genes, implying a functional relationship between SOX2 downregulation and sensitivity. The results show an extensive heterogeneity in BMP4 responsiveness among GICs and identify a BMP4-sensitive subgroup, in which SOX2 is a mediator of the response.

Implications:
Development of agonists targeting the BMP signaling pathway in glioblastoma is an attractive avenue toward a better treatment. Our study may help find biomarkers that predict the outcome of such treatment and enable stratification of patients.
Urothelial Carcinoma of the Bladder Induces Endothelial Cell Activation and Hypercoagulation
Authors: John Axel , Robador José R. , Vidal-y-Sy Sabine , Houdek Pia , Wladykowski Ewa , Günes Cagatay , Bolenz Christian , Schneider Stefan W. , Bauer Alexander T. , Gorzelanny Christian 
Published: March 2020

Abstract

Cancer-related venous thromboembolisms (VTE) are associated with metastasis and reduced survival in patients with urothelial cancer of the bladder. Although previous reports suggest the contribution of tissue factor and podoplanin, the mechanistic linkage between VTE and bladder cancer cell–derived molecules is unknown. Therefore, we compared distinct procoagulant pathways in four different cell lines. In vitro findings were further confirmed by microfluidic experiments mimicking the pathophysiology of tumor blood vessels and in tissue samples of patients with bladder cancer by transcriptome analysis and immunohistology. In vitro and microfluidic experiments identified bladder cancer–derived VEGF-A as highly procoagulant because it promoted the release of von Willebrand factor (VWF) from endothelial cells and thus platelet aggregation. In tissue sections from patients with bladder cancer, we found that VWF-mediated blood vessel occlusions were associated with a poor outcome. Transcriptome data further indicate that elevated expression levels of enzymes modulating VEGF-A availability were significantly connected to a decreased survival in patients with bladder cancer. In comparison with previously postulated molecular players, we identified tumor cell–derived VEGF-A and endothelial VWF as procoagulant mediators in bladder cancer. Therapeutic strategies that prevent the VEGF-A–mediated release of VWF may reduce tumor-associated hypercoagulation and metastasis in patients with bladder cancer.

Implications:
We identified the VEGF-A–mediated release of VWF from endothelial cells to be associated with bladder cancer progression.
Hayr ed-Dîn Barberousse : Un pacha qui n’était pas du sérail
Authors: Vatin Nicolas 
Published: March 2020

Résumé
La promotion de Hayr ed-Dîn Barberousse alimenta des polémiques. Pouvait-on se fier à ce pirate au passé douteux qui n’avait pas suivi le cursus honorum normal ? Les Ġazavât-ı
H

ayr ed-Dîn Paşa répondent à ces accusations : corsaire et non pirate, roi d’Alger qui s’était mis au service de la Porte, Hayr ed-Dîn avait une compétence exceptionnelle de marin et de spécialiste de l’Occident. Pourtant, ni les pachas, ni le sultan ne semblent lui avoir fait entièrement confiance. Directeur de l’Arsenal et non amiral de la flotte, il commanda celle-ci à l’occasion, mais apparemment sous contrôle.
Albert Camus, Metaphysical Revolt, Gnosticism and Modern Cinema
Authors: Roig Lanzillotta Lautaro 
Published: March 2020

Abstract
In The Rebel (1951) Albert Camus assigns ancient Gnosticism an important place in the history of human revolt. In his interpretation, Gnostics incarnate the spirit of proud rebellion and protest against a God deemed responsible for human suffering and death. For Camus these are the roots of metaphysical rebellion in Western history that, beginning in the eighteenth century, culminated in the fascist and socialist utopian experiments in the twentieth century. After assessing Camus’s view of Gnosticism, this article claims that modern cinema shows the impact of The Rebel on the way several recent films conceive of their rebellious protagonists. The controlled character of the revolts they promote shows that modern cinema follows Gnosticism in their analysis both the modern sentiments of alienation in contemporary society and the ways to break free in order to attain a life worthy of its name.
Covariate Extreme Value Analysis Using Wave Spectral Partitioning
Authors: Portilla-Yandún Jesús , Jácome Edwin 
Published: March 2020

AbstractAn important requirement in extreme value analysis (EVA) is for the working variable to be identically distributed. However, this is typically not the case in wind waves, because energy components with different origins belong to separate data populations, with different statistical properties. Although this information is available in the wave spectrum, the working variable in EVA is typically the total significant wave heightHs, a parameter that does not contain information of the spectral energy distribution, and therefore does not fulfill this requirement. To gain insight in this aspect, we develop here a covariate EVA application based on spectral partitioning. We observe that in general the totalHsis inappropriate for EVA, leading to potential over- or underestimation of the projected extremes. This is illustrated with three representative cases under significantly different wave climate conditions. It is shown that the covariate analysis provides a meaningful understanding of the individual behavior of the wave components, in regard to the consequences for projecting extreme values.
Cost‐effectiveness of School Hearing Screening Programs: A Scoping Review
Authors: Yong Michael , Liang Jiahe , Ballreich Jeromie , Lea Jane , Westerberg Brian D. , Emmett Susan D. 
Published: March 2020

ObjectiveSchool hearing screening is a public health intervention that can improve care for children who experience hearing loss that is not detected on or develops after newborn screening. However, implementation of school hearing screening is sporadic and supported by mixed evidence to its economic benefit. This scoping review provides a summary of all published cost‐effectiveness studies regarding school hearing screening programs globally. At the time of this review, there were no previously published reviews of a similar nature.Data SourcesA structured search was applied to 4 databases: PubMed (Medline), Embase, CINAHL, and Cochrane Library.Review MethodsThe database search was carried out by 2 independent researchers, and results were reported in accordance with the PRISMA‐ScR checklist and the JBI methodology for scoping reviews. Studies that included a cost analysis of screening programs for school‐aged children in the school environment were eligible for inclusion. Studies that involved evaluations of only neonatal or preschool programs were excluded.ResultsFour of the 5 studies that conducted a cost‐effectiveness analysis reported that school hearing screening was cost‐effective through the calculation of incremental cost‐effectiveness ratios (ICERs) via either quality‐ or disability‐adjusted life years. One study reported that a new school hearing screening program dominated the existing program; 2 studies reported ICERs ranging from 1079 to 4304 international dollars; and 1 study reported an ICER of £2445. One study reported that school‐entry hearing screening was not cost‐effective versus no screening.ConclusionThe majority of studies concluded that school hearing screening was cost‐effective. However, significant differences in methodology and region‐specific estimates of model inputs limit the generalizability of these findings.
Direct Anticoagulants Versus Vitamin K Antagonists in Patients Aged 80 Years or Older With Atrial Fibrillation in a “Real-world” Nationwide Registry: Insights From the FANTASIIA Study
Authors: Ortiz Martín Ruiz , Muñiz Javier , Esteve-Pastor María Asunción , Marín Francisco , Roldán Inmaculada , Cequier Angel , Martínez-Sellés Manuel , Saldivar Hugo González , Bertomeu Vicente , Anguita Manuel 
Published: March 2020

Objective: To describe major events at follow up in octogenarian patients with atrial fibrillation (AF) according to anticoagulant treatment: direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs). Methods: A total of 578 anticoagulated patients aged ≥80 years with AF were included in a prospective, observational, multicenter study. Basal features, embolic events (stroke and systemic embolism), severe bleedings, and all-cause mortality at follow up were investigated according to the anticoagulant treatment received. Results: Mean age was 84.0 ± 3.4 years, 56% were women. Direct oral anticoagulants were prescribed to 123 (21.3%) patients. Compared with 455 (78.7%) patients treated with VKAs, those treated with DOACs presented a lower frequency of permanent AF (52.9% vs 61.6%, P = .01), cancer history (4.9% vs 10.9%, P = .046), renal failure (21.1% vs 32.2%, P = .02), and left ventricular dysfunction (2.4% vs 8.0%, P = .03); and higher frequency of previous stroke (26.0% vs 16.6%, P = .02) and previous major bleeding (8.1% vs 3.6%, P = .03). There were no significant differences in Charlson, CHA2DS2VASc, nor HAS-BLED scores. At 3-year follow up, rates of embolic events, severe bleedings, and all-cause death (per 100 patients-year) were similar in both groups (DOACs vs VKAs): 0.34 vs 1.35 ( P = .15), 3.45 vs 4.41 ( P = .48), and 8.2 vs 11.0 ( P = .18), respectively, without significant differences after multivariate analysis (hazard ratio [HR]: 0.25, 95% confidence interval [CI]: 0.03-1.93, P = .19; HR: 0.88, 95% CI: 0.44-1.76, P = .72 and HR: 0.84, 95% CI: 0.53-1.33, P = .46, respectively). Conclusion: In this “real-world” registry, the differences in major events rates in octogenarians with AF were not statistically significant in those treated with DOACs versus VKAs.
Functional dyspepsia is associated with lower exercise levels: A population‐based study
Authors: Koloski Natasha A , Jones Michael , Walker Marjorie M , Holtmann Gerald , Talley Nicholas J 
Published: March 2020

BackgroundExercise improves symptoms of irritable bowel syndrome, but few data are available about functional dyspepsia. We compared the prevalence and frequency of different types of exercise between individuals with functional dyspepsia and general population controls.MethodsA mailed survey was returned by 3160 people randomly obtained from the Australian electoral register. The survey included questions to identify the Rome III diagnosis for functional dyspepsia. Exercise was classified by the presence (yes or no) and the frequency (number of times) spent walking, and engaging in moderate and vigorous exercise, over the last 2 weeks based on the National Health Survey. Controls did not meet criteria for functional dyspepsia. Potential confounders included the presence of irritable bowel syndrome, smoking, body mass index, age and gender.ResultsA total of 14.8% (95% confidence interval (CI) 13.6%, 16.1%) subjects had functional dyspepsia. They reported significantly less walking (57% versus 63%, P = 0.04) and lower frequency of exercising, in terms of walking (P = 0.008) and engaging in moderate (P = 0.03) and vigorous activity (P = 0.02), compared with controls. The association remained significant for moderate exercise, independent of age, gender, body mass index and smoking, and excluding overlap with irritable bowel syndrome (odds ratio (OR) = 0.94 (95% CI 0.88, 0.99), P = 0.02). Postprandial distress syndrome was associated with less‐vigorous exercise adjusting for confounders (OR = 0.65 (95% CI 0.42, 1.0), P = 0.05), but not epigastric pain syndrome.ConclusionFunctional dyspepsia is associated with lower exercise levels, but the causality still needs to be determined.
10-year-long survival in a PD patient with severe calcifying encapsulating peritoneal sclerosis treated with tamoxifen: a case-report
Authors: Liakopoulos Vassilios , Georgianos Panagiotis I. , Vaios Vasilios , Roumeliotis Stefanos , Karligkiotis Apostolos , Zebekakis Pantelis E. 
Published: March 2020

Abstract
Background
Encapsulating-peritoneal-sclerosis (EPS) is a rare, but serious and life-threatening complication of peritoneal dialysis (PD). Treatment of EPS consists of discontinuation of PD and maintenance of nutritional status, whereas the role of corticosteroids, tamoxifen and other immunosuppresive agents is not yet fully elucidated.

Case-presentation
We report the case of a 28-year-old patient, who developed a severe form of calcifying EPS after a 6-year-long therapy with automated PD. The clinical presentation was severe with repeated episodes of total bowel obstruction, weight loss and malnutrition that mandated his prolonged hospitalization. Initial treatment included corticosteroids and tamoxifen (20 mg/day) with a clinically meaningful improvement in gastrointestinal function and nutritional status over the first 6–12 months. Corticosteroids were discontinued at 18 months, but owing to persistence of calcifying lesions and peritoneal thickening in repeated computed-tomography (CT) scans, tamoxifen remained unmodified at a low-dose of 20 mg/day for a 10-year-long period. During follow-up, the patient remained symptoms-free in an excellent clinical condition and the CT findings were unchanged.

Conclusions
Long-term administration of tamoxifen was not accompanied by any drug-related adverse effects and potentially exerted a beneficial action on down-regulation of inflammatory and fibrotic processes and improvement of gastrointestinal function, nutritional status and overall health-related quality of life.
The renal range of the κ/λ sFLC ratio: best strategy to evaluate multiple myeloma in patients with chronic kidney disease
Authors: Molina-Andújar Alícia , Robles Pau , Cibeira Maria T. , Montagud-Marrahi Enrique , Guillen Elena , Xipell Marc , Blasco Miquel , Poch Esteban , Rosiñol Laura , Bladé Joan , Quintana Luis F. 
Published: March 2020

Abstract
Background
Monoclonal serum free light chains (sFLC) are a well-known cause of renal impairment (RI) in patients with multiple myeloma (MM). As an indicator of monoclonality, sFLC ratio has acquired a key role in the diagnosis and monitorization of the disease. However, its interpretation is altered in patients with chronic kidney disease (CKD). This study aims to evaluate the modification of the sFLC ratio reference range in patients with CKD, and propose an optimal range for patients with CKD.

Methods
Serum FLC κ/λ ratio and estimated glomerular filtration rate (eGFR) were retrospectively analyzed in 113 control patients (without hematologic disease), 63 patients with MM in complete remission and 347 patients with active MM. The three groups included patients with CKD (eGFR < 90).

Results
In the group of patients without active MM (n = 176), the sFLC ratio increased at different stages of CKD without pathological significance, with an increase in the number of false positives specially when eGFR is ≤55 ml/min. An optimal range was established for patients with eGFR ≤55 ml/min/1.73 m2: 0.82–3,6 with maximum sensitivity + specificity for that group with an improvement in the Area under the curve (AUC), 0.91 (0.84–0.97) compared with the current ranges proposed by Katzmann and Hutchinson.

Conclusions
This study confirms the influence of eGFR on the interpretation of the sFLC ratio, showing a decreasing specificity in progressive CKD stages when using the reference sFLC range (Katzmann), especially in patients with eFGR ≤55. According to our results, we suggest a modified optimal range (0.82–3,6) for eGFR ≤55 ml/min/1.73 m2. It is necessary to validate this modified range in larger and prospective studies.
Accuracy and concordance of measurement methods to assess non-adherence after renal transplantation - a prospective study
Authors: Lieb Marietta , Hepp Tobias , Schiffer Mario , Opgenoorth Mirian , Erim Yesim 
Published: March 2020

Abstract
Background
Non-adherence (NA) to immunosuppressants (IS) among renal transplant recipients (RTRs) is associated with higher risk of allograft rejection, graft loss, and mortality. A precise measurement of NA is indispensable, although its prevalence differs greatly depending on the respective measurement methods. The objective of this study was to assess the accuracy and concordance of different measurement methods of NA in patients after renal transplantation.

Design and methods
This was a single-center prospective observational study. At baseline (T0), NA was measured via physicians’ estimates (PE), self-reports (SR), and tacrolimus trough level variability (CV%) in 78 RTRs. A Visual Analogue Scale (VAS, 0–100%) was applied both for SR and PE. In addition, we used BAASIS© for SR and a 5-point Likert scale for PE. NA was measured prospectively via electronic monitoring (EM, VAICA©) during a three month period. Meanwhile, all participants received phone calls in a two week interval (T1-T6) during which SRs were given.

Results
Seventy-eight RTRs participated in our study. At t0, NA rates of 6.4%, 28.6%, and 15.4% were found for PE, SR, and CV%, respectively. No correlation was found between these methods. During the study, the percentages of self-reported and electronically monitored adherence remained high, with a minimum mean of 91.2% for the strictest adherence measure (Timing Adherence ±30 min). Our results revealed a moderate to high association between SR and EM. In contrast to PE and CV%, SR significantly predicted electronically monitored adherence. Overall, a decreasing effect of electronically monitored adherence was found for both taking and timing adherence (±2 h, ±30 min) over the course of the study.

Discussion
The moderate to high concordance of SR and EM suggests that both methods measure NA equally accurately. SR seems to be a method that can adequately depict electronically monitored NA and may represent a good and economical instrument to assess NA in clinical practice. The increased adherence at the beginning of the study and its subsequent decrease suggests an intervention effect. Surveillance of IS intake via EM with intermittent phone calls could improve adherence on a short-term basis. To establish long-term effects, further research is necessary.