bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apixaban Interacts with Haemoglobin: Effects on Its Plasma Levels
Authors: Sacco Monica , Lancellotti Stefano , Berruti Federico , Arcovito Alessandro , Bellelli Andrea , Ricciardelli Tiziana , Autiero Ida , Cavallo Luigi , Oliva Romina , De Cristofaro Raimondo 
Published: September 2018

AbstractThe direct oral anticoagulant apixaban (APX), a strong factor Xa inhibitor, binds also to plasma proteins, especially albumin, and minimally to α1-acid glycoprotein. Although APX can cross the red cell membrane, due to its chemical structure, and could bind to haemoglobin (Hb), no investigation was performed on this possible phenomenon that could affect the APX plasma concentration and thus its pharmacokinetics and pharmacodynamics. We addressed this issue by (1) measuring the levels of APX and haematological/biochemical parameters in 90 patients on APX therapy; (2) assessing the effect of APX on oxygen saturation curves of Hb; (3) testing the direct APX binding to Hb by fluorescence spectroscopy and a zinc-induced precipitation of Hb coupled to a reversed-phase high-performance liquid chromatography (HPLC)-based method; and (4) simulating in silico by molecular docking the APX interaction with human Hb. In a multivariable analysis, Hb was the only independent variable significantly and inversely associated in 90 patients with APX peak plasma level, at variance with patients treated with rivaroxaban (n = 86) and dabigatran (n = 34) therapy. APX causes a progressive left-shift of the oxygen dissociation curve of purified Hb solution, with a Kd ≅300 µM. Fluorescence- and HPLC-based assays concordantly showed that APX binds to Hb with a Kd ≅350 µM. Finally, docking simulations showed that APX can fit into in the central cavity of Hb. These findings support the hypothesis that APX does bind to Hb, which, due to its millimolar concentration in blood, can act as ‘buffer’ for the drug and consequently affect its free plasma level.
Long Term Follow-up after Endoscopic Endonasal Approach for the Treatment of Cushing's Disease
Authors: Todeschini Alexandre Bossi , Santos Américo Rubens Leite dos , Dolci Ricardo Landini Lutaif , Lima Junior José Viana , Scalissi Nilza Maria , Lazarini Paulo Roberto 
Published: September 2018

Introduction Surgery has been the standard treatment for Cushing's disease. Currently, the endoscopic endonasal approach (EEA) is the most widely used technique. However, among some endocrinologists and neurosurgeons used to the microscope assisted technique, there are still questions about the effectiveness and safety of transitioning to the EEA. We aim to show our initial experience with such transition.
Method Retrospective review of medical records of patients, who underwent EEA in our center as a first treatment for Cushing's disease, and with a minimum 18 months of follow-up, from March 2004 to March 2014
Results Our cohort had 16 patients (14 females and 2 males), with a mean age of 33.7 years. The mean follow-up was 52.0 months. Magnetic resonance imaging (MRI) identified an adenoma in 93.8% of the patients (56.2% microadenomas and 37.5% macroadenomas). Postoperative cerebrospinal fluid (CSF) leak was observed in two patients (12.5%). No new neurological deficits were present after surgery. The early remission and sustained remission rates after a single procedure were 87.5 and 68.75%, respectively. Weight reduction, improved control of blood pressure, and lower serum glucose levels were documented in 68.75, 60, and 55.5% of patients, respectively, after remission.
Conclusion Despite the need for specialized training, equipment and team building by ENT (Ear, Nose and Throat) and neurosurgery, the transition from microscope assisted pituitary surgery to endoscopic endonasal approach is possible and safe. The clinical outcomes, even in the early years, are similar to the previous microscope assisted treatment, and over time, with greater experience and knowledge, there is a tendency for improvement.
Docking of Meprin α to Heparan Sulphate Protects the Endothelium from Inflammatory Cell Extravasation
Authors: Biasin Valentina , Wygrecka Malgorzata , Bärnthaler Thomas , Jandl Katharina , Jain Pritesh , Bálint Zoltán , Kovacs Gabor , Leitinger Gerd , Kolb-Lenz Dagmar , Kornmueller Karin , Peters Florian , Sinn Katharina , Klepetko Walter , Heinemann Akos , Olschewski Andrea , Becker-Pauly Christoph , Kwapiszewska Grazyna 
Published: September 2018

AbstractPulmonary arterial hypertension (PAH) is a rare disease characterized by increased pulmonary pressure and vascular remodelling as a consequence of smooth muscle cell proliferation, endothelial cell dysfunction and inflammatory infiltrates. Meprin α is a metalloproteinase whose substrates include adhesion and cell–cell contact molecules involved in the process of immune cell extravasation. In this study, we aimed to unravel the role of meprin α in PAH-induced vascular remodelling. Our results showed that meprin α was present in the apical membrane of endothelial cells in the lungs and pulmonary arteries of donors and idiopathic PAH (IPAH) patients. Elevated circulating meprin α levels were detected in the plasma of IPAH patients. In vitro binding assays and electron microscopy confirmed binding of meprin α to the glycocalyx of human pulmonary artery endothelial cells (hPAECs). Enzymatic and genetic approaches identified heparan sulphate (HS) as an important determinant of the meprin α binding capacity to hPAEC. Meprin α treatment protected from excessive neutrophil infiltration and the protective effect observed in the presence of neutrophils was partially reversed by removal of HS from hPAEC. Importantly, HS levels in pulmonary arteries were decreased in IPAH patients and binding of meprin α to HS was impaired in IPAH hPAEC. In summary, our results suggest a role of HS in docking meprin α to the endothelium and thus in the modulation of inflammatory cell extravasation. In IPAH, the decreased endothelial HS results in the reduction of meprin α binding which might contribute to enhanced inflammatory cell extravasation and potentially to pathological vascular remodelling.
Pro-Coagulant and Pro-Thrombotic Effects of Paclitaxel Mediated by Red Blood Cells
Authors: Kim Keunyoung , Chang Youn-Kyeong , Bian Yiying , Bae Ok-Nam , Lim Kyung-Min , Chung Jin-Ho 
Published: September 2018

Background Paclitaxel is one of the most widely used anti-cancer drugs, but numerous case reports of thrombotic events in the cancer patients using paclitaxel raise concern over its pro-thrombotic risk.
Materials and Methods We investigated whether paclitaxel can elicit pro-thrombotic properties in red blood cells (RBCs) through phosphatidylserine (PS) exposure and microvesicle (MV) release.
Results In freshly isolated human RBCs, paclitaxel induced thrombin generation through PS exposure and MV release, whereas either coagulation factors or platelets were unaffected. Paclitaxel-induced PS exposure in RBC was mediated by scramblase activation which was induced by calcium-independent protein kinase C (PKC)ζ activation. Paclitaxel also increased RBC-endothelial cell adhesion and RBC aggregate formation which can also contribute to thrombosis. Indeed, intravenous administration of paclitaxel to rats induced PS exposure and PKCζ activation in RBCs in vivo which ultimately promoted venous thrombus formation.
Conclusion These results demonstrated that paclitaxel may elicit pro-thrombotic properties in RBCs through PS exposure and MV release, which can ultimately promote thrombus formation.
Patient-Reported Treatment Satisfaction with Dabigatran versus Warfarin in Patients with Non-Valvular Atrial Fibrillation in China
Authors: Geng Yan-Ping , Lan Di-Hui , Liu Nian , Du Xin , Zheng Danni , Tang Ri-Bo , Long De-Yong , Yu Rong-Hui , Sang Cai-Hua , Bai Rong , Jiang Chen-Xi , Li Song-Nan , Guo Xue-Yuan , Wang Wei , Xia Shi-Jun , Chang San-Shuai , Dong Jian-Zeng , Chen Ai-Hua , Ma Chang-Sheng 
Published: September 2018

Background Anti-coagulant therapy satisfaction for patients with atrial fibrillation is a critical issue, which impacts on their treatment adherence and clinical outcomes. The disadvantages of long-term warfarin treatment are well-described, and novel oral anti-coagulants have become an alternative option.
Materials and Methods We compared patient-reported treatment satisfaction with dabigatran versus warfarin in non-valvular atrial fibrillation (NVAF) patients in China. Treatment satisfaction was assessed using the Anti-Clot Treatment Scale (ACTS) questionnaire, which included a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale.
Results Among 834 patients, 246 patients (29.5%) were taking dabigatran and the others were on warfarin. Propensity score matching was employed to identify 182 patient pairs with balanced baseline characteristics. The global ACTS Burdens score and the global ACTS Benefits score were comparable between the dabigatran and warfarin groups (44.86 ± 3.95 vs. 44.28 ± 3.51, p = 0.423; 11.49 ± 2.92 vs. 11.42 ± 3.03, p = 0.194, respectively). The monthly cost of dabigatran was significantly higher compared with that of warfarin due to a lack of insurance coverage (USD 176.78 ± 9.15 vs. USD 2.49 ± 0.76, p = 0.000). The discontinuation rate of dabigatran was significantly higher than warfarin at the 6-month follow-up (33.5% vs. 19.2%, p = 0.003). Adjusted logistic regression showed that dabigatran was associated with a significant greater odds of non-persistence (odds ratio: 2.13, 95% confidence interval: 1.27–3.59, p = 0.004).
Conclusion Dabigatran therapy in patients with NVAF in China associated with no improvement in satisfaction and a higher discontinuation rate compared with warfarin therapy largely due to increased economic burden.
Anaesthetic Management of a Patient with Subarachnoid Hemorrhage, Multiple Cerebral Aneurysms and Type IV Takayasu Arteritis
Authors: Agrawal Sanket , Gupta Shailesh , Bhagat Hemant , Gandhi Komal , Singla Navneet 
Published: September 2018

AbstractTakayasu's arteritis (TA), also known as pulseless disease, is a granulomatous panarteritis affecting large vessels, predominantly the aorta and its main branches. Twenty percent of TA cases present with central nervous system involvement. It typically manifests as cerebral ischemia or stroke, when central nervous system disease is present. There are rare reports of intracranial aneurysms in adults with TA. We report the anesthetic management of a 16-year old female patient with TA type IV with multiple cerebral aneurysm with subarachnoid hemorrhage.
Psychotherapy training across Europe – status quo
Authors: Weiss E. , Beezhold J. , Eraslan D. , Gerber S. , Hanon C. , Mihai A. 
Published: September 2018

SummaryPsychotherapy is an essential part of being a psychiatrist. International professional associations including the World Psychiatric Association (WPA), European Psychiatric Association (EPA), Union of European Medical Specialists (UEMS), European Federation of Psychiatric Trainees (EFPT) are involved in sustaining the role of psychotherapy training as part of psychiatric education as a matter of policy. This article presents results of a survey by trainees from different European countries concerning the postgraduate training in psychotherapy. We explore how national or international organisations have influenced and changed psychotherapy training in this region. Short descriptions of the situation in a few European countries offer an overview of different approach. There is no “one size fits all” solution concerning the training in psychotherapy like part of psychiatric training; however local resources and international exchanges could be used towards harmonising standards and quality.
Predicting polymorphism in molecular crystals using orientational entropy
Authors: Piaggi Pablo M. , Parrinello Michele 
Published: September 2018

Significance
Small organic molecules often exhibit an amazing polymorphism. Since most drugs are based on organic molecules, this has important practical consequences. Not only does the deliverability of the drugs depend on the crystal structure but also different polymorphs can be separately patented. We address this problem by appropriately designed enhanced sampling simulations that start from the liquid and let the system crystallize spontaneously at the freezing temperature. In such a way entropy effects are automatically included. We successfully apply the method to the cases of urea and naphthalene and discover that entropy plays an important role.
Small Degree of Lumbar Lordosis as an Overlooked Determinant for Orthostatic Increases in Blood Pressure in the Elderly: The Nagahama Study
Authors: Tabara Yasuharu , Masaki Mitsuhiro , Ikezoe Tome , Setoh Kazuya , Kato Takehiro , Kawaguchi Takahisa , Kosugi Shinji , Nakayama Takeo , Ichihashi Noriaki , Tsuboyama Tadao , Matsuda Fumihiko ,   Nagahama Study Group
Published: September 2018

Abstract

BACKGROUND
Orthostatic hypertension was associated with worse cardiovascular outcomes, although the factors responsible for an orthostatic rise in blood pressure (BP) are uncertain. We investigated a possible relationship between a stooping posture and orthostatic BP change.

METHODS
Study participants consisted of 1,992 older individuals. Orthostatic BP change was calculated by systolic BP measured at sitting position, and again 1 and 3 minutes after standing up. Spinal alignment and curvature was assessed by guiding the SpinalMouse device on the surface of the skin along the spine.

RESULTS
Mean lumbar lordosis at standing position was 13.4° ± 12.4°. The degree of lumbar lordosis was significantly smaller in orthostatic hypertensive individuals (systolic BP change, ≥+20 mm Hg: 3.3° ± 15.6°, ≥+10 mm Hg: 10.4° ± 14.3°) than in individuals who were orthostatic normotensive (14.2° ± 11.9°). Multiple linear regression analysis identified lumbar lordosis (β = −0.171, P &lt; 0.001) and thoracic kyphosis (β = 0.062, P = 0.007), but not sacral inclination (β = 0.033, P = 0.303), as independent determinants for orthostatic BP change. As waist circumference was another independent determinant, the frequency of orthostatic hypertensive individuals was linearly increased with the combination of abdominal obesity and small degree of lumbar lordosis (control: 9.9%, abdominal obesity: 17.4%, small degree of lordosis: 19.4%, both: 24.1%, P &lt; 0.001). Participants who sustained orthostatic hypertension for 3 minutes after standing up had the smallest degree of lumbar lordosis (5.2° ± 16.4°).

CONCLUSION
Stooped posture was an overlooked determinant for orthostatic increases in BP.
PRESM: personalized reference editor for somatic mutation discovery in cancer genomics
Authors: Cao Chen , Mak Lauren , Jin Guangxu , Gordon Paul , Ye Kai , Long Quan 
Published: September 2018

Abstract

Motivation
Accurate detection of somatic mutations is a crucial step toward understanding cancer. Various tools have been developed to detect somatic mutations from cancer genome sequencing data by mapping reads to a universal reference genome and inferring likelihoods from complex statistical models. However, read mapping is frequently obstructed by mismatches between germline and somatic mutations on a read and the reference genome. Previous attempts to develop personalized genome tools are not compatible with downstream statistical models for somatic mutation detection.

Results
We present PRESM, a tool that builds personalized reference genomes by integrating germline mutations into the reference genome. The aforementioned obstacle is circumvented by using a two-step germline substitution procedure, maintaining positional fidelity using an innovative workaround. Reads derived from tumor tissue can be positioned more accurately along a personalized reference than a universal reference due to the reduced genetic distance between the subject (tumor genome) and the target (the personalized genome). Application of PRESM’s personalized genome reduced false-positive (FP) somatic mutation calls by as much as 55.5%, and facilitated the discovery of a novel somatic point mutation on a germline insertion in PDE1A, a phosphodiesterase associated with melanoma. Moreover, all improvements in calling accuracy were achieved without parameter optimization, as PRESM itself is parameter-free. Hence, similar increases in read mapping and decreases in the FP rate will persist when PRESM-built genomes are applied to any user-provided dataset.

Availability and implementation
The software is available at https://github.com/precisionomics/PRESM.

Supplementary information
Supplementary data are available at Bioinformatics online.
MetaOmics: analysis pipeline and browser-based software suite for transcriptomic meta-analysis
Authors: Ma Tianzhou , Huo Zhiguang , Kuo Anche , Zhu Li , Fang Zhou , Zeng Xiangrui , Lin Chien-Wei , Liu Silvia , Wang Lin , Liu Peng , Rahman Tanbin , Chang Lun-Ching , Kim Sunghwan , Li Jia , Park Yongseok , Song Chi , Oesterreich Steffi , Sibille Etienne , Tseng George C 
Published: September 2018

Abstract

Summary
The rapid advances of omics technologies have generated abundant genomic data in public repositories and effective analytical approaches are critical to fully decipher biological knowledge inside these data. Meta-analysis combines multiple studies of a related hypothesis to improve statistical power, accuracy and reproducibility beyond individual study analysis. To date, many transcriptomic meta-analysis methods have been developed, yet few thoughtful guidelines exist. Here, we introduce a comprehensive analytical pipeline and browser-based software suite, called MetaOmics, to meta-analyze multiple transcriptomic studies for various biological purposes, including quality control, differential expression analysis, pathway enrichment analysis, differential co-expression network analysis, prediction, clustering and dimension reduction. The pipeline includes many public as well as &gt;10 in-house transcriptomic meta-analytic methods with data-driven and biological-aim-driven strategies, hands-on protocols, an intuitive user interface and step-by-step instructions.

Availability and implementation
MetaOmics is freely available at https://github.com/metaOmics/metaOmics.

Supplementary information
Supplementary data are available at Bioinformatics online.
Measurement Equivalence of the Subjective Well-Being Scale Among Racially/Ethnically Diverse Older Adults
Authors: Kim Giyeon , Wang Sylvia Y , Sellbom Martin 
Published: September 2018

Abstract

Objectives
The present study examined differences by race/ethnicity in the measurement equivalence of the Subjective Well-Being Scale (SWBS) among older adults in the United States.

Method
Drawn from the National Health and Aging Trends Study (NHATS), adults aged 65 years and older from three racial/ethnic groups (n = 1,200) were selected for the analyses from a total of 8,245: 400 non-Hispanic Whites, 400 African Americans, and 400 Hispanics/Latinos. We tested measurement equivalence of the SWBS that is categorized into three domains: positive and negative affect (four items), self-realization (four items), and self-efficacy and resilience (three items). Multiple-group confirmatory factor analyses were conducted to test measurement invariance.

Results
After adjusting for age, gender, and education, the underlying construct of the SWBS was noninvariant across three racial/ethnic elderly groups.

Discussion
Findings suggest that the comparison of latent means (especially for positive and negative affect and self-realization) across racial/ethnic groups is highly questionable. The SWBS should be used with extreme caution when it is applied to diverse racial/ethnic elderly groups for comparison purposes. Implications are discussed in cultural and methodological contexts.
Clouds in arms
Authors: Belokurov Vasily A , Erkal Denis 
Published: September 2018

ABSTRACT
We use astrometry and broad-band photometry from Data Release 2 of the ESA’s Gaia mission to map out low surface-brightness features in the stellar density distribution around the Large and Small Magellanic Clouds. The LMC appears to have grown two thin and long stellar streams in its Northern and Southern regions, highly reminiscent of spiral arms. We use computer simulations of the Magellanic Clouds’ in-fall to demonstrate that these arms were likely pulled out of the LMC’s disc due to the combined influence of the SMC’s most recent fly-by and the tidal field of the Milky Way.
Hepatitis C Within a Single Health System: Progression Along the Cascade to Cure Is Higher for Those With Substance Misuse When Linked to a Clinic With Embedded Support Services
Authors: Sherbuk J E , McManus K A , Rogawski McQuade E T , Knick T , Henry Z , Dillingham R 
Published: September 2018

Abstract

Background
Hepatitis C is now curable for most individuals, and national goals for elimination have been established. Transmission persists, however, particularly in nonurban regions affected by the opioid epidemic. To reach goals of elimination, barriers to treatment must be identified.

Methods
In this open cohort of all individuals diagnosed with active hepatitis C from 2010 to 2016 at a large medical center, we identified patient and clinic characteristics associated with our primary outcome, sustained virologic response (SVR). We performed a subgroup analysis for those with documented substance misuse.

Results
SVR was achieved in 1544 (41%) of 3790 people with active hepatitis C. In a multivariable Poisson regression model, SVR was more likely in individuals diagnosed outpatient (incident rate ratio [IRR], 1.7; 95% confidence interval [CI], 1.5–2.0), living in close proximity to the medical center (IRR, 1.2; 95% CI, 1.1–1.3), with private insurance (IRR, 1.1; 95% CI, 1.0–1.3), and with cirrhosis (IRR, 1.4; 95% CI, 1.3–1.5). Achieving SVR was less likely in those qualifying as indigent (IRR, 0.8; 95% CI, 0.8–0.9) and those with substance misuse (IRR, 0.8; 95% CI, 0.7–0.9). In the subgroup analysis of those with substance misuse, SVR rates were higher in those linked to the infectious diseases clinic, which has embedded support services, than those linked to the gastroenterology clinic, which does not (IRR, 1.4; 95% CI, 1.1–1.9).

Conclusions
Social determinants of health including proximity to care and poverty impacted achievement of SVR. Those with substance misuse, a high-priority population for treatment of hepatitis C, had better outcomes when receiving care in a clinic with embedded support services.
Matters of Method
Authors: Mastroianni George R. 
Published: September 2018

Abstract
Chapter 3 explores issues in the application of the traditional methods of psychological science to understanding the Holocaust. Three such issues are (a) What is the nature of available “data” in studying the Holocaust? (b) Can contemporary laboratory research inform our understanding of the Holocaust? (c) Can we reconcile the exculpatory implications of a deterministic analysis with our moral assessment of the Holocaust? Psychologists accustomed to exerting considerable control over the data they produce and study confront considerable challenges in the use of historical data. Laboratory research, while potentially relevant to the Holocaust, similarly presents considerable challenges in assessing the generalizability of such findings to temporally and culturally distant events. Insofar as psychological explanations are framed in the vernacular of social science, the risk of such explanations being seen as inappropriately exculpatory cannot be avoided.