bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ticagrelor versus clopidogrel in stent-assisted coil embolization of unruptured intracranial aneurysms
Authors: Chien Shuo-Chi , Chen Ching-Chang , Chen Chun-Ting , Wang Alvin Yi-Chou , Hsieh Po-Chuan , Yeap Mun-Chun , Liu Zhuo-Hao , Wang Yu-Chi , Liu Yu-Tse 
Published: November 2021

Background Dual antiplatelet therapy is widely used for stent-assisted coil embolization (SACE) for unruptured intracranial aneurysms (UIAs) to prevent thromboembolic events (TEs). Compared to clopidogrel associated with aspirin, knowledge of the safety and efficacy of ticagrelor is lacking in large studies to date. Methods A retrospective cohort study was conducted from January 2016 to December 2018 with at least one year of follow-up in a single institution and systemic review. Results Altogether, 153 patients with UIA receiving SACE were separated into two groups: 113 patients receiving clopidogrel plus aspirin and 40 patients receiving ticagrelor plus aspirin. Acute in-stent thrombotic events were noted in two patients in the clopidogrel group (1.77%) and none in the ticagrelor group (0%). Additionally, one patient (0.88%) in the clopidogrel group had an early ischemic stroke (<3 months). Delayed ischemic stroke was noted in 6 patients (5.31%) in the clopidogrel group and 3 patients (7.50%) in the ticagrelor group. There were no major hemorrhagic events in either group. The two groups showed no significant differences with regard to ischemic stroke or hemorrhagic stroke. Conclusion Compared to the clopidogrel based regimen, ticagrelor can also reduce TEs without increasing bleeding tendency for SACE of UIAs. Ticagrelor combined with low-dose aspirin is a safe and effective alternative option for SACE.
Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy
Authors: Sharma Mukul , Smith Eric E , Pearce Lesly A , Perera Kanjana S , Kasner Scott E , Yoon Byung-Woo , Ameriso Sebastian F , Puig Josep , Damgaard Dorte , Fiebach Jochen B , Muir Keith W , Veltkamp Roland C , Toni Danilo S , Shamalov Nikolay , Gagliardi Rubens J , Mikulik Robert , Engelter Stefan T , Bereczki Daniel , O’Donnell Martin J , Saad Feryal , Shoamanesh Ashkan , Berkowitz Scott D , Mundl Hardi , Hart Robert G ,   On behalf of the NAVIGATE ESUS MRI Substudy Investigators
Published: November 2021

Background Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. Aims To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. Methods At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. Results Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52–1.7). Conclusions Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide. Registration: https://www.clinicaltrials.gov . Unique identifier: NCT 02313909
Estimating nocturnal stroke onset times by magnetic resonance imaging in the WAKE-UP trial
Authors: Cheng Bastian , Pinnschmidt Hans , Königsberg Alina , Schlemm Eckhard , Boutitie Florent , Ebinger Martin , Endres Matthias , Fiebach Jochen B , Fiehler Jens , Galinovic Ivana , Lemmens Robin , Muir Keith W , Pedraza Salvador , Puig Josep , Simonsen Claus Z , Thijs Vincent , Wouters Anke , Gerloff Christian , Thomalla Götz 
Published: November 2021

Background Fluid-attenuated inversion recovery (FLAIR) sequences have gained a role to guide treatment of patients with unknown time of stroke symptom onset. Evolution of signal intensities in FLAIR is associated with time since stroke onset with continuous linear increases. Aims Estimating symptom onset during night-sleep in patients from the WAKE-UP trial based on relative signal intensities FLAIR (FLAIR-rSI) from acute stroke lesions an independent dataset (PRE-FLAIR study). Methods FLAIR-rSI was quantified in stroke lesions in PRE-FLAIR and WAKE-UP. The PRE-FLAIR study was a multicenter observational trial establishing FLAIR as a surrogate parameter for time since stroke onset. WAKE-UP was a randomized controlled trial that revealed a benefit for alteplase in patients selected based on a DWI-FLAIR mismatch. Stroke onset times were recorded in PRE-FLAIR and used to fit a linear regression model with FLAIR-rSI, adjusted for patient age and lesion volume. The model was applied to FLAIR-rSI of stroke lesions to estimate onset times in those patients enrolled in WAKE-UP who had symptom onset during night-sleep. Results FLAIR-rSI was quantified in 399 patients from PRE-FLAIR. Linear regression indicated a significant association of age ( p = 0.001), lesion volume ( p = 0.005) and FLAIR-rSI ( p < 0.001) with time since symptom onset (adjusted R2 = 0.179). In 813 patients from WAKE-UP, distribution of times of last seen well, symptom recognition and MRI examination were recorded. Median times of last seen well were 1 h before midnight (IQR 2.4 h) and symptom recognition 7 h after midnight (IRQ 2.2 h). Based on the FLAIR-rSI profiles, we estimated median stroke onset 6.1 h after midnight (IQR 2.7 h). Conclusion Nocturnal strokes during night-sleep may predominantly occur during the early morning hours. Our results are in line with evidence of characteristic diurnal patterns of cardiovascular events.
Iterative reconstruction improves image quality and reduces radiation dose in trauma protocols; A human cadaver study
Authors: Godt Johannes Clemens , Johansen Cathrine K , Martinsen Anne Catrine T , Schulz Anselm , Brøgger Helga M , Jensen Kristin , Stray-Pedersen Arne , Dormagen Johann Baptist 
Published: November 2021

Background Radiation-related cancer risk is an object of concern in CT of trauma patients, as these represent a young population. Different radiation reducing methods, including iterative reconstruction (IR), and spilt bolus techniques have been introduced in the recent years in different large scale trauma centers. Purpose To compare image quality in human cadaver exposed to thoracoabdominal computed tomography using IR and standard filtered back-projection (FBP) at different dose levels. Material and methods Ten cadavers were scanned at full dose and a dose reduction in CTDIvol of 5 mGy (low dose 1) and 7.5 mGy (low dose 2) on a Siemens Definition Flash 128-slice computed tomography scanner. Low dose images were reconstructed with FBP and Sinogram affirmed iterative reconstruction (SAFIRE) level 2 and 4. Quantitative image quality was analyzed by comparison of contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR). Qualitative image quality was evaluated by use of visual grading regression (VGR) by four radiologists. Results Readers preferred SAFIRE reconstructed images over FBP at a dose reduction of 40% (low dose 1) and 56% (low dose 2), with significant difference in overall impression of image quality. CNR and SNR showed significant improvement for images reconstructed with SAFIRE 2 and 4 compared to FBP at both low dose levels. Conclusions Iterative image reconstruction, SAFIRE 2 and 4, resulted in equal or improved image quality at a dose reduction of up to 56% compared to full dose FBP and may be used a strong radiation reduction tool in the young trauma population.
One year follow-up and exploratory analysis of a patient-centered interdisciplinary care intervention for multimorbidity
Authors: Fortin Martin , Stewart Moira , Almirall José , Berbiche Djamal , Bélanger Mathieu , Katz Alan , Ryan Bridget L , Wong Sabrina T , Zwarenstein Merrick 
Published: November 2021

Context Interventions for people with multimorbidity have obtained mixed results. We aimed to document the long-term effect of an intervention for people with multimorbidity. Methods 284 patients (18–80 years) presenting three or more chronic conditions were recruited from seven family medicine groups in the Saguenay-Lac St-Jean region, Quebec, Canada. The patient-centered intervention was based on motivational approach and self-management support. Outcomes were evaluated in a one-year pre-post study design with questionnaires that included the Health Education Questionnaire (heiQ), the Self-Efficacy for Managing Chronic Diseases, the Veteran RAND-12 Health Survey (VR-12), the EuroQoL 5-Domains questionnaire, the Kessler six item Psychological Stress Scale, and measures of smoking habit, physical activity, healthy eating and alcohol consumption. Subgroup analyses by age, number of conditions, sex, and income were also conducted. Results The heiQ domain of emotional wellbeing improved significantly. Improvement was also observed for the VR-12 and the K6. Among the health behaviours, only healthy eating was improved. Subgroup analyses in this exploratory study suggest that younger patients, those with lower number of chronic conditions or higher incomes may respond better in relation to self-management, health status and health behaviours. Conclusion One year after the intervention, participants significantly improved a variety of outcomes. Subgroup analyses suggest that younger patients, those with lower number of chronic conditions or higher incomes may respond better in relation to self-management, health status and health behaviours. This suggests that future interventions should be tailored to patients’ characteristics including age, sex, income and number of conditions.
Differential impact of IDH1/2 mutational subclasses on outcome in adult AML: results from a large multicenter study
Authors: Middeke Jan M. , Metzeler Klaus H. , Röllig Christoph , Krämer Michael , Eckardt Jan-Niklas , Stasik Sebastian , Greif Philipp A. , Spiekermann Karsten , Rothenberg-Thurley Maja , Krug Utz , Braess Jan , Krämer Alwin , Hochhaus Andreas , Brümmendorf Tim H. , Naumann Ralph , Steffen Björn , Einsele Hermann , Schaich Markus , Burchert Andreas , Neubauer Andreas , Görlich Dennis , Sauerland Cristina , Schäfer-Eckart Kerstin , Schliemann Christoph , Krause Stefan W. , Hänel Mathias , Frickhofen Norbert , Noppeney Richard , Kaiser Ulrich , Kaufmann Martin , Kunadt Desiree , Wörmann Bernhard , Sockel Katja , von Bonin Malte , Herold Tobias , Müller-Tidow Carsten , Platzbecker Uwe , Berdel Wolfgang E. , Serve Hubert , Baldus Claudia D. , Ehninger Gerhard , Schetelig Johannes , Hiddemann Wolfgang , Bornhäuser Martin , Stölzel Friedrich , Thiede Christian 
Published: November 2021

Abstract
Mutations of the isocitrate dehydrogenase-1 (IDH1) and IDH2 genes are among the most frequent alterations in acute myeloid leukemia (AML) and can be found in ∼20% of patients at diagnosis. Among 4930 patients (median age, 56 years; interquartile range, 45-66) with newly diagnosed, intensively treated AML, we identified IDH1 mutations in 423 (8.6%) and IDH2 mutations in 575 (11.7%). Overall, there were no differences in response rates or survival for patients with mutations in IDH1 or IDH2 compared with patients without mutated IDH1/2. However, distinct clinical and comutational phenotypes of the most common subtypes of IDH1/2 mutations could be associated with differences in outcome. IDH1-R132C was associated with increased age, lower white blood cell (WBC) count, less frequent comutation of NPM1 and FLT3 internal tandem mutation (ITD) as well as with lower rate of complete remission and a trend toward reduced overall survival (OS) compared with other IDH1 mutation variants and wild-type (WT) IDH1/2. In our analysis, IDH2-R172K was associated with significantly lower WBC count, more karyotype abnormalities, and less frequent comutations of NPM1 and/or FLT3-ITD. Among patients within the European LeukemiaNet 2017 intermediate- and adverse-risk groups, relapse-free survival and OS were significantly better for those with IDH2-R172K compared with WT IDH, providing evidence that AML with IDH2-R172K could be a distinct entity with a specific comutation pattern and favorable outcome. In summary, the presented data from a large cohort of patients with IDH1/2 mutated AML indicate novel and clinically relevant findings for the most common IDH mutation subtypes.
Using chest CT scan and unsupervised machine learning for predicting and evaluating response to lumacaftor-ivacaftor in people with cystic fibrosis
Authors: Campredon Alienor , Battistella Enzo , Martin Clémence , Durieu Isabelle , Mely Laurent , Marguet Christophe , Belleguic Chantal , Murris-Espin Marlène , Chiron Raphaël , Fanton Annlyse , Bui Stéphanie , Reynaud-Gaubert Martine , Reix Philippe , Hoang-Thi Trieu-Nghi , Vakalopoulou Maria , Revel Marie-Pierre , Da Silva Jennifer , Burgel Pierre-Régis , Chassagnon Guillaume 
Published: November 2021

ObjectivesLumacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator known to improve clinical status in people with cystic fibrosis (CF). This study aimed to assess lung structural changes after one year of lumacaftor-ivacaftor treatment, and to use unsupervised machine learning to identify morphological phenotypes of lung disease that are associated with response to lumacaftor-ivacaftor.MethodsAdolescents and adults with CF from the French multicenter real-world prospective observational study evaluating the first year of treatment with lumacaftor-ivacaftor were included if they had pretherapeutic and follow-up chest computed tomography (CT)-scans available. CT scans were visually scored using a modified Bhalla score. A k-mean clustering method was performed based on 120 radiomics features extracted from unenhanced pretherapeutic chest CT scans.ResultsA total of 283 patients were included. The Bhalla score significantly decreased after 1 year of lumacaftor-ivacaftor (−1.40±1.53 points compared with pretherapeutic CT; p<0.001). This finding was related to a significant decrease in mucus plugging (−0.35±0.62 points; p<0.001), bronchial wall thickening (−0.24±0.52 points; p<0.001) and parenchymal consolidations (−0.23±0.51 points; p<0.001). Cluster analysis identified 3 morphological clusters. Patients from cluster C were more likely to experience an increase in percent predicted forced expiratory volume in 1 sec (ppFEV1) ≥5 under lumacaftor–ivacaftor than those in the other clusters (54% of responders versus 32% and 33%; p=0.01).ConclusionOne year treatment with lumacaftor-ivacaftor was associated with a significant visual improvement of bronchial disease on chest CT. Radiomics features on pretherapeutic CT scan may help in predicting lung function response under lumacaftor-ivacaftor.
Asc-Seurat: analytical single-cell Seurat-based web application
Authors: Pereira W. J. , Almeida F. M. , Conde D. , Balmant K. M. , Triozzi P. M. , Schmidt H. W. , Dervinis C. , Pappas G. J. , Kirst M. 
Published: November 2021

Abstract
Background
Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of transcriptomes, arising as a powerful tool for discovering and characterizing cell types and their developmental trajectories. However, scRNA-seq analysis is complex, requiring a continuous, iterative process to refine the data and uncover relevant biological information. A diversity of tools has been developed to address the multiple aspects of scRNA-seq data analysis. However, an easy-to-use web application capable of conducting all critical steps of scRNA-seq data analysis is still lacking.

Summary
We present Asc-Seurat, a feature-rich workbench, providing an user-friendly and easy-to-install web application encapsulating tools for an all-encompassing and fluid scRNA-seq data analysis. Asc-Seurat implements functions from the Seurat package for quality control, clustering, and genes differential expression. In addition, Asc-Seurat provides a pseudotime module containing dozens of models for the trajectory inference and a functional annotation module that allows recovering gene annotation and detecting gene ontology enriched terms. We showcase Asc-Seurat’s capabilities by analyzing a peripheral blood mononuclear cell dataset.

Conclusions
Asc-Seurat is a comprehensive workbench providing an accessible graphical interface for scRNA-seq analysis by biologists. Asc-Seurat significantly reduces the time and effort required to analyze and interpret the information in scRNA-seq datasets.
Genome-wide characterization and analysis of WRKY transcription factors in Panax ginseng
Authors: Di Peng , Wang Ping , Yan Min , Han Peng , Huang Xinyi , Yin Le , Yan Yan , Xu Yonghua , Wang Yingping 
Published: November 2021

Abstract
Background
Panax ginseng is a well-known medicinal plant worldwide. As an herbal medicine, ginseng is also known for its long lifecycle, which can reach several decades. WRKY proteins play regulatory roles in many aspects of biological processes in plants, such as responses to biotic or abiotic stress, plant development, and adaptation to environmental challenges. Genome-wide analyses of WRKY genes in P. ginseng have not been reported.

Results
In this study, 137 PgWRKY genes were identified from the ginseng genome. Phylogenetic analysis showed that the PgWRKYs could be clustered into three primary groups and five subgroups. Most of the PgWRKY gene promoters contained several kinds of hormone- and stress-related cis-regulatory elements. The expression patterns of PgWRKY genes in 14 different tissues were analyzed based on the available public RNA-seq data. The responses of the PgWRKY genes to heat, cold, salt and drought treatment were also investigated. Most of the PgWRKY genes were expressed differently after heat treatment, and expression trends changed significantly under drought and cold treatment but only slightly under salt treatment. The coexpression analysis of PgWRKY genes with the ginsenoside biosynthesis pathway genes identified 11 PgWRKYs that may have a potential regulatory role in the biosynthesis process of ginsenoside.

Conclusions
This work provides insights into the evolution, modulation and distribution of the WRKY gene family in ginseng and extends our knowledge of the molecular basis along with modulatory mechanisms of WRKY transcription factors in ginsenoside biosynthesis.
Euthanasia in advanced dementia; the view of the general practitioners in the Netherlands on a vignette case along the juridical and ethical dispute
Authors: Schuurmans Jaap , Crol Chantalle , Chabot Boudewijn , Olde Rikkert Marcel , Engels Yvonne 
Published: November 2021

Abstract
Background
In the Netherlands, euthanasia has been regulated by law since 2002. In the past decade, a growing number of persons with dementia requested for euthanasia, and more requests were granted. A euthanasia request from a patient with advanced dementia (PWAD) can have a major impact on a general practitioner (GP). We aimed to get insights in the views of Dutch GPs on euthanasia concerning this patient group.

Methods
A postal survey was sent to 894 Dutch GPs. Questions were asked about a case vignette about a PWAD who was not able to confirm previous wishes anymore. Quantitative data were analyzed with descriptive statistics.

Results
Of the 894 GPs approached, 422 (47.3%) completed the survey. One hundred seventy-eight GPs (42.2%) did not agree with the statement that an Advance Euthanasia Directive (AED) can replace an oral request if communication with the patient concerned has become impossible. About half of the respondents (209; 49.5%) did not agree that the family can initiate a euthanasia trajectory, 95 GPs (22.5%) would accept such a family initiative and 110 GPs (26.1%) would under certain conditions.

Discussion
In case of a PWAD, when confirming previous wishes is not possible anymore, about half of the Dutch GPs would not accept an AED to replace verbal or non-verbal conformation nor consider performing euthanasia; a minority would. Our study shows that, probably due to the public debate and changed professional guidelines, conflicting views have arisen among Dutch GPs about interpretation of moral, ethical values considering AED and PWADs.
Independent associations of thyroid-related hormones with hepatic steatosis and insulin resistance in euthyroid overweight/obese Chinese adults
Authors: Ma Danyan , Zeng Jinyang , Huang Bingkun , Yan Fangfang , Ye Jiawen , Chen Yun , Zeng Xiying , Zheng Xin , Xiao Fangsen , Lin Mingzhu , Liu Changqin , Li Zhibin 
Published: November 2021

Abstract
Purpose
The aim of the study is to explore the independent association of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) with hepatic steatosis and insulin resistance.

Methods
A cross-sectional study of 88 overweight/obese adults who underwent anthropometric measurements [BMI, waist circumference (WC) and waist-to-height ratio (WHtR)], hepatic steatosis assessment (FibroScan) and thyroid-related hormones tests was conducted from 2018 to 2020 in Xiamen, China.

Results
Subjects with increasing tertiles of FT3 showed significantly higher levels of controlled attenuation parameter (CAP) ((295.4 ± 44.1, 290.1 ± 68.2 and 331.7 ± 43.6 (dB/m) for tertile 1–3, respectively, p = 0.007) and fatty liver index (FLI) score (47.7 (33.9–60.8), 61.5 (45.1–88.9) and 90.5 (84.5–94.8), respectively, p < 0.001). FT3 significantly and positively correlated with obesity index (BMI, WC, and WHtR), homeostatic model assessment of insulin resistance (HOMA-IR) and hepatic steatosis (CAP and FLI). Multivariable linear regression analyses with adjustment for potential confounding factors showed FT3 was independently associated with BMI (regression coefficient (β (95%CI): 0.024 (0.004–0.043), p = 0.020), HOMA-IR (β (95%CI): 0.091 (0.007–0.174), p = 0.034), CAP (β (95%CI): 25.45 (2.59–48.31), p = 0.030) and FLI (β (95%CI): 0.121 (0.049–0.194), p = 0.001). Neither FT4 nor TSH was significantly associated with any indicators of obesity, insulin resistance or hepatic steatosis.

Conclusions
Increased FT3, but not FT4 or TSH, was independently associated with higher risks of hepatic steatosis and insulin resistance in euthyroid overweight/obese Chinese adults.
Trial registration Registration is not applicable for our study.