bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host-Based Virtual Machine Workload Characterization Using Hypervisor Trace Mining
Authors: Nemati Hani , Azhari Seyed Vahid , Shakeri Mahsa , Dagenais Michel 
Published: June 2021

Cloud computing is a fast-growing technology that provides on-demand access to a pool of shared resources. This type of distributed and complex environment requires advanced resource management solutions that could model virtual machine (VM) behavior. Different workload measurements, such as CPU, memory, disk, and network usage, are usually derived from each VM to model resource utilization and group similar VMs. However, these course workload metrics require internal access to each VM with the available performance analysis toolkit, which is not feasible with many cloud environments privacy policies.
In this article, we propose a non-intrusive host-based virtual machine workload characterization using hypervisor tracing. VM blockings duration, along with virtual interrupt injection rates, are derived as features to reveal multiple levels of resource intensiveness. In addition, the VM exit reason is considered, as well as the resource contention rate due to the host and other VMs. Moreover, the processes and threads preemption rates in each VM are extracted using the collected tracing logs. Our proposed approach further improves the selected features by exploiting a page ranking based algorithm to filter non-important processes running on each VM. Once the metric features are defined, a two-stage VM clustering technique is employed to perform both coarse- and fine-grain workload characterization. The inter-cluster and intra-cluster similarity metrics of the silhouette score is used to reveal distinct VM workload groups, as well as the ones with significant overlap. The proposed framework can provide a detailed vision of the underlying behavior of the running VMs. This can assist infrastructure administrators in efficient resource management, as well as root cause analysis.
Recurrent Mutations in Cyclin D3 Confer Clinical Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia
Authors: Smith Catherine C. , Viny Aaron D. , Massi Evan , Kandoth Cyriac , Socci Nicholas D. , Rapaport Franck , Najm Matthieu , Medina-Martinez Juan S. , Papaemmanuil Elli , Tarver Theodore C. , Hsu Henry H. , Le Mai H. , West Brian , Bollag Gideon , Taylor Barry S. , Levine Ross L. , Shah Neil P. 
Published: June 2021

Abstract

Purpose:
Biomarkers of response and resistance to FLT3 tyrosine kinase inhibitors (TKI) are still emerging, and optimal clinical combinations remain unclear. The purpose of this study is to identify co-occurring mutations that influence clinical response to the novel FLT3 inhibitor pexidartinib (PLX3397).

Experimental Design:
We performed targeted sequencing of pretreatment blasts from 29 patients with FLT3 internal tandem duplication (ITD) mutations treated on the phase I/II trial of pexidartinib in relapsed/refractory FLT3-ITD+ acute myeloid leukemia (AML). We sequenced 37 samples from 29 patients with available material, including 8 responders and 21 non-responders treated at or above the recommended phase II dose of 3,000 mg.

Results:
Consistent with other studies, we identified mutations in NRAS, TP53, IDH2, and a variety of epigenetic and transcriptional regulators only in non-responders. Among the most frequently mutated genes in non-responders was Cyclin D3 (CCND3). A total of 3 individual mutations in CCND3 (Q276*, S264R, and T283A) were identified in 2 of 21 non-responders (one patient had both Q276* and S264R). No CCND3 mutations were found in pexidartinib responders. Expression of the Q276* and T283A mutations in FLT3-ITD MV4;11 cells conferred resistance to apoptosis, decreased cell-cycle arrest, and increased proliferation in the presence of pexidartinib and other FLT3 inhibitors. Inhibition of CDK4/6 activity in CCND3 mutant MV4;11 cells restored pexidartinib-induced cell-cycle arrest but not apoptosis.

Conclusions:
Mutations in CCND3, a gene not commonly mutated in AML, are a novel cause of clinical primary resistance to FLT3 inhibitors in AML and may have sensitivity to CDK4/6 inhibition.
AXL Inhibition in Macrophages Stimulates Host-versus-Leukemia Immunity and Eradicates Naïve and Treatment-Resistant Leukemia
Authors: Tirado-Gonzalez Irene , Descot Arnaud , Soetopo Devona , Nevmerzhitskaya Aleksandra , Schäffer Alexander , Kur Ivan-Maximilano , Czlonka Ewelina , Wachtel Carolin , Tsoukala Ioanna , Müller Luise , Schäfer Anna-Lena , Weitmann Maresa , Dinse Petra , Alberto Emily , Buck Michèle C. , Landry Jonathan JM. , Baying Bianka , Slotta-Huspenina Julia , Roesler Jenny , Harter Patrick N. , Kubasch Anne-Sophie , Meinel Jörn , Elwakeel Eiman , Strack Elisabeth , Quang Christine Tran , Abdel-Wahab Omar , Schmitz Marc , Weigert Andreas , Schmid Tobias , Platzbecker Uwe , Benes Vladimir , Ghysdael Jacques , Bonig Halvard , Götze Katharina S. , Rothlin Carla V. , Ghosh Sourav , Medyouf Hind 
Published: June 2021

Abstract

Acute leukemias are systemic malignancies associated with a dire outcome. Because of low immunogenicity, leukemias display a remarkable ability to evade immune control and are often resistant to checkpoint blockade. Here, we discover that leukemia cells actively establish a suppressive environment to prevent immune attacks by co-opting a signaling axis that skews macrophages toward a tumor-promoting tissue repair phenotype, namely the GAS6/AXL axis. Using aggressive leukemia models, we demonstrate that ablation of the AXL receptor specifically in macrophages, or its ligand GAS6 in the environment, stimulates antileukemic immunity and elicits effective and lasting natural killer cell– and T cell–dependent immune response against naïve and treatment-resistant leukemia. Remarkably, AXL deficiency in macrophages also enables PD-1 checkpoint blockade in PD-1–refractory leukemias. Finally, we provide proof-of-concept that a clinical-grade AXL inhibitor can be used in combination with standard-of-care therapy to cure established leukemia, regardless of AXL expression in malignant cells.

Significance:
Alternatively primed myeloid cells predict negative outcome in leukemia. By demonstrating that leukemia cells actively evade immune control by engaging AXL receptor tyrosine kinase in macrophages and promoting their alternative priming, we identified a target which blockade, using a clinical-grade inhibitor, is vital to unleashing the therapeutic potential of myeloid-centered immunotherapy.
This article is highlighted in the In This Issue feature, p. 2659
Does Local Coherence Lead to Targeted Regressions and Illusions of Grammaticality?
Authors: Paape Dario , Vasishth Shravan , Engbert Ralf 
Published: June 2021

Abstract
Local coherence effects arise when the human sentence processor is temporarily misled by a locally grammatical but globally ungrammatical analysis (The coach smiled at the player tossed a frisbee by the opposing team). It has been suggested that such effects occur either because sentence processing occurs in a bottom-up, self-organized manner rather than under constant grammatical supervision, or because local coherence can disrupt processing due to readers maintaining uncertainty about previous input. We report the results of an eye-tracking study in which subjects read German grammatical and ungrammatical sentences that either contained a locally coherent substring or not and gave binary grammaticality judgments. In our data, local coherence affected on-line processing immediately at the point of the manipulation. There was, however, no indication that local coherence led to illusions of grammaticality (a prediction of self-organization), and only weak, inconclusive support for local coherence leading to targeted regressions to critical context words (a prediction of the uncertain-input approach). We discuss implications for self-organized and noisy-channel models of local coherence.
A tipping point for open citation data
Authors: Hutchins B. Ian 
Published: June 2021

Abstract
Open citation data can improve the transparency and robustness of scientific portfolio analysis, improve science policy decision-making, stimulate downstream commercial activity, and increase the discoverability of scientific articles. Once sparsely populated, public-domain citation databases crossed a threshold of one billion citations in February 2021. Shortly thereafter, the threshold of one billion public domain citations from the Crossref database alone was crossed. As the relative advantage of withholding data in closed databases has diminished with the flood of public domain data, this likely constitutes an irreversible change in the citation data ecosystem. The successes of this movement can guide future open data efforts.
“Spoiling” in the Public Sphere: Political Opposition to Peace Negotiations and the Referendum Campaign in Colombia
Authors: Amaral Joana 
Published: June 2021

Abstract
Peace referendums can be exploited by political actors who may gain politically from opposing a peace process. This article explores how political opposition affects peace negotiations, particularly when a referendum is used to ratify an agreement, through the study of the Colombian peace negotiations between the government of President Santos and the Revolutionary Armed Forces of Colombia (FARC). It finds that the exclusive character of the negotiations, coupled with their confidentiality, contributed to the political opposition’s capacity to influence public opinion against the peace process and to reject the peace agreement in the 2016 referendum. This qualitative study is based on the content analysis of reports, memoirs and interviews with key negotiation delegates, journalists and representatives of the referendum campaigns. It argues that political inclusion in peace negotiations can help prevent referendum spoiling, while public information and education during the negotiations can reduce the impact of disinformation and manipulation campaigns.
Vascularity Outcomes of Lingual Artery Ligation in Transoral Robotic Base of Tongue Resections
Authors: Dunlap Quinn , Mitchell William M. , Gardner James Reed , King Deanne , Samant Rohan , Moreno Mauricio , Vural Emre 
Published: June 2021

To explore the effect of lingual artery ligation on tongue vascularity, we performed an analysis of 25 patients who underwent transoral robotic surgery for base of tongue cancers (May 2011 to December 2019). Hounsfield units of the intrinsic muscles (IMs) and genioglossus muscles (GGs) were measured in postoperative imaging (mean 4 months) as a surrogate for vascularity. In ligated patients (n = 15), the values from the ligated/resected side of the tongue were compared with the contralateral side and the nonligated side of resection. Individually, IMs and GGs on the ligated side demonstrated no significant difference to the contralateral side (P =. 662 and. 618, respectively). Ligation produced a significant decrease in IM measurements but no difference between GG values vs nonligated patients (P =. 050 and. 818, respectively). No difference was appreciated in mean values for combined IMs and GGs between cohorts (P =. 212). No gross tongue atrophy or complications were incurred. Future studies are warranted to delineate long‐term effects.
Examining fruit and vegetable intake in low-income older adults using the Veggie Meter®
Authors: Fultz Amanda Kopetsky , Rex Samantha M. , Mazelin Audrey , McGarry Charlotte , Brewer Ben , Patterson Freda , Robson Shannon 
Published: June 2021

Background: Older adults report low fruit and vegetable (FV) intake. The lack of objective, field-based assessments of FV intake is a limitation when assessing the effectiveness of interventions. Aim: To examine if self-reported FV intake was correlated with Veggie Meter® scores among low-income older adults. The Veggie Meter® is a portable tool that uses pressure-mediated reflection spectroscopy to estimate skin carotenoid measurements. Methods: A cross-sectional assessment of FV intake, food security, and Veggie Meter® score in low-income older adults was conducted. Bivariate analyses quantified the association between FV intake and Veggie Meter® score. Results: Participants ( n = 154) were mostly female (69.3%), non-white (66.2%) and at risk for food insecurity (65.6%). Mean Veggie Meter® score was 172.3 ± 77.2 and had a small significant positive correlation with FV intake (r= 0.192, p = 0.018). Conclusion: The Veggie Meter® may objectively indicate FV intake. Research to validate the Veggie Meter® in older, diverse populations is needed.
Use of Intravenous Vitamin C in Critically Ill Patients With COVID-19 Infection
Authors: Li Matthew , Ching Tsung Han , Hipple Christopher , Lopez Ricardo , Sahibzada Asad , Rahman Habibur 
Published: June 2021

Introduction The pathophysiology for Coronavirus Disease 2019 (COVID-19) infection is characterized by cytokine oxidative stress and endothelial dysfunction. Intravenous (IV) vitamin C has been utilized as adjuvant therapy in critically ill patients with sepsis for its protective effects against reactive oxygen species and immunomodulatory effects. The primary objective of this study was to evaluate the effects of IV vitamin C in critically ill patients with COVID-19 infection. Methods Retrospective observational cohort study with propensity score matching of intensive care unit (ICU) patients who received 1.5 grams IV vitamin C every 6 hours for up to 4 days for COVID-19 infection. The primary study outcome was in-hospital mortality. Secondary outcomes included vasopressor requirements in norepinephrine equivalents, ICU length of stay, and change in Sequential Organ Failure Assessment (SOFA) score. Results Eight patients received IV vitamin C and were matched to 24 patients. Patients in the IV vitamin C group had higher rates of hospital mortality [7 (88%) vs. 19 (79%), P = 0.049]. There was no difference in the daily vasopressor requirement in the treatment group or between the 2 groups. The mean SOFA scores post-treatment was higher in the IV vitamin C group (12.4 ± 2.8 vs. 8.1 ± 3.5, P < 0.005). There was no difference in ICU length of stay between the treatment and control groups. Conclusion Adjunctive IV vitamin C for the management of COVID-19 infection in critically ill patients may not decrease the incidence of mortality, vasopressor requirements, SOFA scores, or ventilator settings.
Long-time dynamics of a class of nonlocal extensible beams with time delay
Authors: Meng Fengjuan , Liu Cuncai , Zhang Chang 
Published: June 2021

This work is devoted to the following nonlocal extensible beam equation with time delay: [Formula: see text] on a bounded smooth domain [Formula: see text]. The main purpose of this paper is to consider the long-time dynamics of the system. Under suitable assumptions, the quasi-stability property of the system is established, based on which the existence and regularity of a finite-dimensional compact global attractor are obtained. Moreover, the existence of exponential attractors is proved.
Open Capsulorrhaphy for Recurrent Multidirectional Instability of the Shoulder
Authors: Bolia Ioanna K. , Griffith Rebecca , Fretes Nickolas , Petrigliano Frank A. 
Published: June 2021

Background: The management of multidirectional instability (MDI) of the shoulder remains challenging, especially in athletes who participate in sports and may require multiple surgical procedures to achieve shoulder stabilization. Open or arthroscopic procedures can be performed to address shoulder MDI. Indications: Open capsulorrhaphy is preferred in patients with underlying tissue hyperlaxity and who had 1 or more, previously failed, arthroscopic shoulder stabilization procedures. Technique Description: With the patient in the beach-chair position (45°), tissue dissection is performed to the level of subscapularis tendon via the deltopectoral approach. The subscapularis tenotomy is performed in an L-shaped fashion, and the subscapularis tendon is tagged with multiple sutures and mobilized. Careful separation of the subscapularis tendon from the underlying capsular tissue is critical. Capsulotomy is performed, consisting of a vertical limb and an inferior limb that extends to the 5 o’clock position on the humeral neck (right shoulder). After evaluating the integrity of the labrum, the capsule is shifted superiorly and laterally, and repaired using 4 to 5 suture anchors. The redundant capsule is excised, and the subscapularis tendon is repaired in a side-to-side fashion, augmented by transosseous equivalent repair using the capsular sutures. Results: Adequate shoulder stabilization was achieved following open capsulorrhaphy in a young female athlete with tissue hyperlaxity and history of a previously failed arthroscopic soft tissue stabilization surgery of the shoulder. The athlete returned to sport at 6 months postoperatively and did not experience recurrent shoulder instability episodes at midterm follow-up. Discussion/Conclusion: Based on the existing literature, 82% to 97% of patients who underwent open capsulorrhaphy for MDI had no recurrent shoulder instability episodes at midterm follow-up. One study reported 64% return-to-sport rate following open capsulorrhaphy in 15 adolescent athletes with Ehlers-Danlos syndrome, but more research is necessary to better define the indications and outcomes of this procedure in physically active patients.
A Study on the Effect of the Structural Parameters and Internal Mechanism of a Bilateral Gate-Controlled S/D Symmetric and Interchangeable Bidirectional Tunnel Field Effect Transistor
Authors: Jin Xiaoshi , Wang Yicheng , Ma Kailu , Wu Meile , Liu Xi , Lee Jong-Ho 
Published: June 2021

AbstractA bilateral gate-controlled S/D symmetric and interchangeable bidirectional tunnel field effect transistor (B-TFET) is proposed in this paper, which shows the advantage of bidirectional switching characteristics and compatibility with CMOS integrated circuits compared to the conventional asymmetrical TFET. The effects of the structural parameters, e.g., the doping concentrations of the N+ region and P+ region, length of the N+ region and length of the intrinsic region, on the device performances, e.g., the transfer characteristics, Ion–Ioff ratio and subthreshold swing, and the internal mechanism are discussed and explained in detail.
The GEnetic Syntax Score: a genetic risk assessment implementation tool grading the complexity of coronary artery disease—rationale and design of the GESS study
Authors: Vizirianakis Ioannis S. , Chatzopoulou Fani , Papazoglou Andreas S. , Karagiannidis Efstratios , Sofidis Georgios , Stalikas Nikolaos , Stefopoulos Christos , Kyritsis Konstantinos A. , Mittas Nikolaos , Theodoroula Nikoleta F. , Lampri Aggeliki , Mezarli Eleni , Kartas Anastasios , Chatzidimitriou Dimitrios , Papa-Konidari Anna , Angelis Eleftherios , Karvounis Ηaralambos , Sianos Georgios 
Published: June 2021

Abstract
Background
Coronary artery disease (CAD) remains one of the leading causes of mortality worldwide and is associated with multiple inherited and environmental risk factors. This study is designed to identify, design, and develop a panel of genetic markers that combined with clinical and angiographic information, will facilitate the creation of a personalized risk prediction algorithm (GEnetic Syntax Score—GESS). GESS score could be a reliable tool for predicting cardiovascular risk for future adverse events and for guiding therapeutic strategies.

Methods
GESS (ClinicalTrials.gov Identifier: NCT03150680) is a prospective, non-interventional clinical study designed to enroll 1080 consecutive patients with no prior history of coronary revascularization procedure, who undergo scheduled or emergency coronary angiography in AHEPA, University General Hospital of Thessaloniki. Next generation sequencing (NGS) technology will be used to genotype specific single-nucleotide polymorphisms (SNPs) across the genome of study participants, which were identified as clinically relevant to CAD after extensive bioinformatic analysis of literature-based SNPs. Enrichment analyses of Gene Ontology-Molecular Function, Reactome Pathways and Disease Ontology terms were also performed to identify the top 15 statistically significant terms and pathways. Furthermore, the SYNTAX score will be calculated for the assessment of CAD severity of all patients based on their angiographic findings. All patients will be followed-up for one-year, in order to record any major adverse cardiovascular events.

Discussion
A group of 228 SNPs was identified through bioinformatic and pharmacogenomic analysis to be involved in CAD through a wide range of pathways and was correlated with various laboratory and clinical parameters, along with the patients' response to clopidogrel and statin therapy. The annotation of these SNPs revealed 127 genes being affected by the presence of one or more SNPs. The first patient was enrolled in the study in February 2019 and enrollment is expected to be completed until June 2021. Hence, GESS is the first trial to date aspiring to develop a novel risk prediction algorithm, the GEnetic Syntax Score, able to identify patients at high risk for complex CAD based on their molecular signature profile and ultimately promote pharmacogenomics and precision medicine in routine clinical settings.
Trial registration GESS trial registration: ClinicalTrials.gov Number: NCT03150680. Registered 12 May 2017- Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT03150680.
The application of artificial intelligence methods to gene expression data for differentiation of uncomplicated and complicated appendicitis in children and adolescents - a proof of concept study –
Authors: Reismann Josephine , Kiss Natalie , Reismann Marc 
Published: June 2021

Abstract
Background
Genome wide gene expression analysis has revealed hints for independent immunological pathways underlying the pathophysiologies of phlegmonous (PA) and gangrenous appendicitis (GA). Methods of artificial intelligence (AI) have successfully been applied to routine laboratory and sonographic parameters for differentiation of the inflammatory manifestations. In this study we aimed to apply AI methods to gene expression data to provide evidence for feasibility.

Methods
Modern algorithms from AI were applied to 56.666 gene expression data sets from 13 patients with PA and 16 with GA aged 7–17 years by using resampling methods (bootstrap). Performance with respect to sensitivities and specificities where investigated with receiver operating characteristic (ROC) analysis.

Results
Within the experimental setting a best performing discriminatory biomarker signature consisting of a set of 4 genes could be defined: ERGIC and golgi 3, regulator of G-protein signaling 2, Rho GTPase activating protein 33, and Golgi Reassembly Stacking Protein 2. ROC analysis showed a mean area under the curve of 84%.

Conclusions
Gene expression based application of AI methods is feasible and represents a promising approach for future discriminatory diagnostics in children with acute appendicitis.