bluuebunny/crossref_metadata_2025_split huggingface dataset:
Composable Finite State Machine-based Modeling for Quality-of-Information-aware Cyber-physical Systems
Authors: Rosales Rafael , Paulitsch Michael 
Published: July 2020

Time plays a major role in the
specification of Cyber-physical Systems (CPS) behavior
with concurrency, timeliness, asynchrony, and resource limits as their main characteristics. In addition to
timeliness
, the specification of CPS needs to assess and unambiguously define its behavior with respect to the other Quality-of-Information (QoI) properties: (1) Correctness, (2) Completeness, (3) Consistency, and (4) Accuracy. Very often, CPS need to handle these QoI properties, and any combination thereof, multiple times when performing computation and communication processes. However, a model-driven and systematic approach to specify CPS behavior that jointly considers combined QoI aspects is possible but missing in existing methodologies.

As the first contribution of this work, we provide an extension to an established model of computation (MoC) based on “Functions driven by Finite State Machine” (FunState) to enable a model-driven
composition mechanism
to create CPS behavior specifications from reusable components.

Second, we present a novel set of
design patterns
to illustrate the modeling of
QoI-aware CPS specifications
that can be applied in several state-of-the-art Electronic System Level (ESL) methodologies. The time semantics of the MoC are formalized using the tagged-signal-model, and the presented model-driven approach enables the composition of multiple design patterns.

The main benefits of the presented model-driven approach and design patterns to create CPS specifications are as follows: (a) reduce modeling effort, errors, and time through the reuse of known recipes to re-incurring tasks and allow to automatically generate repetitive control flows based on extended Finite State Machines; (b) increase system robustness and facilitate the creation of holistic QoI management allowing to unambiguously define system behavior for scenarios with single/multiple QoI requirement violations in different models of computation; (c) dynamically validate timing behavior of system implementations to enable a multi-objective optimization of nonfunctional properties that influence CPS timing.
We demonstrate the aforementioned benefits through the modeling and evaluation of an infrastructure-assisted automated driving case study using Infrastructure-to-Vehicle (I2V) communications to distribute QoI critical road environment information.
Predictors of Postoperative Radiation Following Laser Resection in Early‐Stage Glottic Cancer
Authors: Silverman Dustin A. , Zhan Kevin Y. , Puram Sidharth V. , Eskander Antoine , Teknos Theodoros N. , Rocco James W. , Old Matthew O. , Kang Stephen Y. 
Published: July 2020

ObjectiveGuideline recommendations for the treatment of early‐stage glottic cancer are limited to single‐modality therapy with surgery or radiation alone. We sought to investigate the clinicopathologic and treatment factors associated with the use of postoperative radiation therapy (PORT) following laser excision for patients with T1‐T2N0 glottic squamous cell carcinoma (SCC).Study DesignRetrospective observational study of the National Cancer Database.SettingNational Cancer Database review from 2004 to 2014.Patients and MethodsA total of 1338 patients with primary cT1‐T2N0M0 glottic SCC undergoing primary laser excision were included. Hospitals were divided into quartiles based on yearly volume of laryngeal laser cases performed. Multivariate logistic regression was performed to identify independent predictors of PORT.ResultsThe overall rate of PORT was 30.0%. Predictors of PORT included treatment at lower‐volume hospitals (adjusted odds ratio [aOR] for quartiles 2‐4, 1.32‐4.84), positive margins (aOR, 3.83 [95% CI, 2.54‐5.78]), and T2 tumors (aOR, 3.58 [95% CI, 2.24‐5.74]). PORT utilization demonstrated a strong inverse correlation with hospital volume. Among top‐quartile hospitals, the rate of PORT was 11.2%, while rates of PORT at second‐, third‐, and fourth‐quartile institutions were 19.2%, 32.2%, and 37.4%, respectively.ConclusionsPredictors of PORT in multivariable analysis included treatment at lower‐volume facilities, positive margins, and T2 disease. This study highlights the importance of treating early‐stage glottic carcinoma at high‐volume institutions. In addition, there is a need to reevaluate the use of PORT and reduce the rate of dual‐modality therapy for patients with early‐stage glottic SCC.
miR-146a alleviates the apoptosis of hippocampal neurons induced by microglia activation via targeting TRAF6
Authors: Jia J , Liu C , Han Y , Han H , Zhong M , Gao Y 
Published: July 2020

Objective: To identify the role of miR-146a and tumor necrosis factor receptor-associated factor 6 (TRAF6) for improving the apoptosis of hippocampal neurons induced by microglia activation. Methods: Mouse microglial cell line (BV2 cell) was employed and treated with lipopolysaccharide. Mouse hippocampal nerve cell line (HT22 cell) was then grown in BV2 conditioned medium, and miR-146a overexpression and silencing cell lines were constructed. CCK8 and clone formation test were utilized to evaluate the proliferation ability of the transfected cells, and the level of inflammatory factors was measured by ELISA. Apoptosis was determined extensively by flow cytometry. The apoptosis-related protein and TRAF6 protein expressions were verified by Western blot. TRAF6 was identified to be the target gene of miR-146a based on double Luciferase Report. Finally, both TRAF6 and miR-146a were used to treat HT22 cells and the above indexes were detected repeatedly. Results: Interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 expressions in BV2 cells increased significantly. miR-146a overexpression distinctly increased the cell proliferation ability and B-cell lymphoma-2 expression ((Bcl-2, p < 0.05); meanwhile, the apoptosis rate of cells, apoptosis-related proteins (Bcl-2 associated X and cleaved caspase-3), and TRAF6 gene and protein expressions were significantly decreased ( p < 0.05). However, these above results were reversed for miR-146a silence. There is a targeting relationship between miR-146a and TRAF6. Silencing TRAF6 gene can promote HT22 cells’ proliferation and inhibit apoptosis. The effect of miR-146a on HT22 cells was reversed by adding TRAF6 mimics to miR-146a overexpression cells. Conclusion: miR-146a can inhibit the apoptosis of hippocampal neurons caused by microglia activation via targeting TRAF6 and down-regulating its expression.
Myocardial injury in systemic lupus erythematosus according to cardiac magnetic resonance tissue characterization: clinical and echocardiographic features
Authors: du Toit Riëtte , Herbst Phillip G , Ackerman Christelle , Pecoraro Alfonso JK , du Toit Rudolf HR , Hassan Karim , Joubert LLoyd H , Reuter Helmuth , Doubell Anton F 
Published: July 2020

Objectives To determine the prevalence of myocardial injury (MInj) in systemic lupus erythematosus (SLE) according to cardiac magnetic resonance (CMR) criteria. To compare clinical and echocardiographic features of patients with and without MInj and identify predictors of myocardial tissue characteristics according to CMR. Methods SLE inpatients underwent CMR screening for MInj based on the Lake Louise Criteria (LLC). Tissue characteristics included inflammation (increased T2-weighted signal or early gadolinium enhancement ratio (EGEr)) and necrosis or fibrosis (late gadolinium enhancement (LGE)). Echocardiographic parameters included left (left ventricular ejection fraction (LVEF)) and right ventricular function (tricuspid annular plane systolic excursion (TAPSE)), global longitudinal strain (GLS), wall motion score (WMSi) and left ventricular internal diameter index (LVIDi). Variables were compared with regards to the presence/absence of CMR criteria. Logistic regression identified variables predictive of CMR tissue characteristics. Results A hundred and six SLE patients were screened of whom 49 patients were included. Fifty-seven patients were excluded due to intolerance of or contraindication to CMR (27/57 due to renal impairment). Twenty-three patients had CMR evidence of MInj, of which 60.9% was subclinical. Inflammation occurred in 16/23 and necrosis/fibrosis in 12/23 patients. Patients with any evidence of MInj were more frequently anti-dsDNA positive ( p = 0.026) and patients fulfilling LLC for myocarditis had higher SLE disease activity ( p = 0.022). The LVIDi ( p = 0.005), LVEF ( p = 0.005) and TAPSE ( p = 0.011) were more abnormal in patients with an increased EGEr, whereas WMSi ( p = 0.002) and GLS (0.020) were more impaired in patients with LGE. On multivariable logistic regression analyses, TAPSE predicted inflammation (OR: 0.045, p = 0.006, CI: 0.005–0.415) and GLS predicted necrosis/fibrosis (OR: 1.329, p = 0.031, CI: 1.026–1.722). A model including lymphocyte count, TAPSE and LVIDi predicted an increased EGEr on CMR (receiver operating characteristic-curve analyses: area under the curve: 0.901, p < 0.001, sensitivity: 88.9%, specificity: 76.3%). Conclusions CMR evidence of MInj frequently occurs in SLE and is often subclinical. The utility of CMR in SLE is limited by a high exclusion rate, mainly due to renal involvement. Models including echocardiographic parameters (TAPSE, LVIDi and GLS) are predictive of CMR myocardial injury. Echocardiography can be used as a cost-effective screening tool with a high negative predictive value, in particular when CMR is contraindicated or unavailable.
Characterization and analysis of exhaust pipe (muffler) contact burns: An unsuspecting culprit
Authors: Hansen Trevor C , Patel Alap U , Pencek Megan E , Bell Derek E 
Published: July 2020

Introduction Thermal injury due to contact with engine exhaust systems represents a distinct subgroup of acute contact burns. Temperatures generated by motor vehicle, radiator, and lawn mower engines can exceed 250℃, at which point relatively deep tissue loss occurs with less than 0.06 seconds of cutaneous exposure. While prior studies have helped elucidate the demographic characteristics of exhaust pipe contact burns, our analysis was aimed at both demographics and burn severity, as indicated by rate of full-thickness injury and requirement for tangential excision and skin grafting. Methods Data were obtained from a retrospective review of admissions at a regional burn center between 1 July 2012 and 30 August 2016. Patients of all ages with muffler, exhaust, motorcycle, lawn mower, and radiator burn injuries were included. Extensive demographic information, percent total body surface area burned (TBSA), burn etiology and location, third-degree and fourth-degree burn percentage, and subsequent operative information were analyzed for patients who sustained exhaust pipe contact burns. These data were then compared with all contact burn injuries from the same time period, matched for %TBSA range, using Fisher exact and unpaired t-tests. Results A total of 110 patients suffered exhaust pipe contact burns during the study period; 65 (59%) were males, and mean age was 30. Nearly two thirds of the muffler burns were sustained from motorcycles with TBSA ranging from 0.05% to 3.14%; at least 61% had some third-degree burn. The average number of operating room visits per patient was 0.54, though this varied significantly, with 38 patients (35%) requiring 59 total surgeries (range 1–6). Muffler burn patients were older than the matched control group. The most common location of burn injury was the lower leg with no difference between adults and children. Pediatric patients understandably had smaller burn surface area but similar TBSA compared to adults. The majority of injuries occurred in May, June, and July. Conclusions Exhaust pipe contact burns comprise a specific subset of low %TBSA contact burns with relatively high morbidity, evidenced by a significantly higher proportion of full-thickness tissue loss and eventual need for skin grafting when compared with nonexhaust burn controls. Awareness of the increased severity of exhaust pipe contact burns may lead to more expedient surgical intervention as well as further education regarding preventative measures.
Reclassifying severity after 48 hours could better predict mortality in acute respiratory distress syndrome
Authors: Chiu Li-Chung , Lin Shih-Wei , Liu Pi-Hua , Chuang Li-Pang , Chang Chih-Hao , Hung Chen-Yiu , Li Shih-Hong , Lee Chung-Shu , Wu Huang-Pin , Huang Chung-Chi , Li Hsin-Hsien , Kao Kuo-Chin , Hu Han-Chung 
Published: July 2020

Background: Disease severity may change in the first week after acute respiratory distress syndrome (ARDS) onset. The aim of this study was to evaluate whether the reclassification of disease severity after 48 h (i.e. day 3) of ARDS onset could help in predicting mortality and determine factors associated with ARDS persistence and mortality. Methods: We performed a secondary analysis of a 3-year prospective, observational cohort study of ARDS in a tertiary care referral center. Disease severity was reclassified after 48 h of enrollment, and cases that still fulfilled the Berlin criteria were regarded as nonresolving ARDS. Results: A total of 1034 ARDS patients were analyzed. Overall hospital mortality was 57.7% (56.7%, 57.5%, and 58.6% for patients with initial mild, moderate, and severe ARDS, respectively, p = 0.189). On day 3 reclassification, the hospital mortality rates were as follows: resolved (42.1%), mild (47.9%), moderate (62.4%), and severe ARDS (76.1%) ( p < 0.001). Patients with improving severity on day 3 had lower mortality (48.8%), whereas patients with the same or worsening severity on day 3 had higher mortality (62.7% and 76.3%, respectively). Patients who were older, had lower PaO2/FiO2, or higher positive end-expiratory pressure on day 1 were significantly associated with nonresolving ARDS on day 3. A Cox regression model with ARDS severity as a time-dependent covariate and competing risk analysis demonstrated that ARDS severity was independently associated with hospital mortality, and nonresolving ARDS had significantly increased hazard of death than resolved ARDS ( p < 0.0001). Cumulative mortality curve for ARDS severity comparisons demonstrated significantly different (overall comparison, p < 0.001). Conclusions: Reclassification of disease severity after 48 h of ARDS onset could help to divide patients into subgroups with greater separation in terms of mortality. The reviews of this paper are available via the supplemental material section.
Randomized Pilot Trial of Acute Normovolemic Hemodilution in Pediatric Cardiac Surgery Patients
Authors: Harris Weronika M. , Treggiari Miriam M. , LeBlanc Ashleigh , Giacomuzzi Carmen , You Jayme J. , Muralidaran Ashok , Shen Irving 
Published: July 2020

Background: Due to the substantial improvement in survival among pediatric patients undergoing congenital heart surgery, reducing early and long-term morbidity is becoming the major focus of care. Blood transfusion is associated with worse postoperative outcomes after cardiac surgery. Acute normovolemic hemodilution (ANH) is a blood conservation strategy that aims to reduce allogenic blood transfusion during cardiac surgery. However, there are scant data regarding its efficacy for pediatric cardiac surgery patients. Methods: We designed a single-center, controlled, randomized, pilot trial in patients between 6 and 36 months old undergoing pediatric heart surgery. Patients were equally assigned to undergo ANH prior to initiation of cardiopulmonary bypass or to be managed per usual care. The primary end point was the amount of blood product transfused perioperatively. Secondary end points were markers of morbidity: postoperative bleeding, hematocrit, inotropic agents use, intensive care unit, and hospital stay. The analysis was by intention-to-treat. Estimates of differences between groups are presented with 95% CIs. Results: Twelve pediatric heart surgery patients were randomized to each group, ANH and usual care. Baseline characteristics were similar between groups. Acute normovolemic hemodilution implementation did not result in a reduction in the administration of blood product transfused (difference between ANH and usual care among patients transfused = −1.4 mL [−29.4 to 26.6], P = .92). Secondary end points were not different between groups. Conclusions: In this small trial of pediatric cardiac surgery patients, ANH as a strategy to reduce blood component therapy was safe; however, the study failed to show a reduction in perioperative transfusion or other postoperative outcomes.
Does Intramedullary Nailing for Distal Fibular Fractures Restore Anatomic Parameters and Syndesmotic Relationship?
Authors: Mikenberg Natalio R. Cuchacovich , Gallardo Francisco J. Bravo , Giannini Esteban , Astudillo Claudia , Pellegrini Manuel J. , Muñoz Gerardo , Melo Rodrigo , Cortes Aaron , Bastias Gonzalo F. 
Published: July 2020

Category: Trauma; Ankle Introduction/Purpose: Fibular nailing (FN) is a method of fixation that has proven to be useful for the treatment of distal fibular fractures (DF). FN minimizes soft tissue complications, provides similar stability compared to plating with less hardware related symptoms. Nevertheless, FN has been associated with syndesmotic malreduction and incapacity of restoring length and rotation of the fibula. We aimed to evaluate the fibular and syndesmotic reduction after fixation with FN compared to the uninjured ankle. Methods: Prospective cohort, cross-sectional study with a paired control group. Patients with DF fractures treated with FN between January 2017 and July 2019 were included. Immediate postoperative bilateral Ankle CT was obtained in all cases. Two independent radiologists performed all the measurements on both ankles (fibular rotation, length, translation, and syndesmotic diastasis. Statistical analysis was made using the Wilcoxon Test and Intraclass correlation coefficient (ICC). Considering a medium size sample effect, 95% confidence with .05 alpha error, a total sample of 26 subjects were needed to achieve a .80 of statistical power (G-Power 3.1). All analyses were performed using SPSS V20. Results: Twenty-six patients were included (14 Women). The mean age was 47 years (18-91). No statistically significant differences were identified considering fibular rotation (p:0,694), fibular length (p:0,585) and syndesmotic diastasis (p:0,078) between the injured and uninjured ankle. Fibular translation has statistical differences (p:0,043). The ICC shows an excellent concordance between radiologists except for Fibular translation (ICC 0,47) Conclusion: In this cohort, fixation of DF fractures with FN allows restoration of anatomical parameters of the ankle in terms of fibular rotation, length, and syndesmotic diastasis. However, Fibular translation had significant differences compared with the uninjured ankle.
Hindfoot Alignment after Total Ankle Replacement
Authors: Gross Christopher E. , Usuelli Federico Guiseppe , Indino Christian 
Published: July 2020

Category: Ankle Arthritis; Ankle Introduction/Purpose: End-stage ankle arthritis can involve misalignment of the ankle in both the coronal and sagittal planes as up to reported 33% to 44% of patients who present for total ankle replacement have greater than 10° of coronal plane deformity. Improvements in both the design and surgical technique for total ankle replacements (TAR) have allowed surgeons to tackle the most challenging of multiplanar ankle deformities. Normalization of the sagittal and coronal alignment is key in improving survivorship and functional outcomes in TAR. In the present study, we analyzed how both the ankle and hindfoot alignment for both a fixed-bearing and mobile bearing TAR system changes over time. Specifically, we measured coronal and sagittal alignment of both the ankle and hindfoot complex. We hypothesize that both significant differences would be seen between all time points and pre-operative radiographs, and that these differences would not change over time. Methods: A retrospective study performed by a single orthopaedic surgeon was performed on two independent groups of patients undergoing two different systems for total ankle replacement: Zimmer TAR (lateral-approach, fixed-bearing, n=89) and Hintegra (anterior approach, mobile-bearing, n=81). We noted specific demographic data and radiographic data were measured including: Hindfoot alignment view angle (HAV), Hindfoot alignment distance (HAVD), tibiotalar ratio, α angle and β angle. These were measured pre-operatively, and 6 months, 12 months, and 24 months post-operatively. Within-group comparisons were performed using one-way repeated-measures ANOVA (1-w rANOVA), analyzing temporal course of clinical data (comparisons between different time points, e.g. T0vsT6vsT12vsT24) within the Hintegra and Zimmer groups. To compare the time course of clinical measures between the two groups, 2-w rANOVAs were performed for SA, SD, TT ratio, α and β angle. Specifically, time*group interaction was tested. Results: At the ankle joint itself, as measured by the α and β angles (p>.05), the position of the components remains relatively similar in both the fixed and mobile bearing TAR over the course of 24 months. The sagittal alignment, as measured by the TT ratio, demonstrated a posterior shifting of the talus in the mobile bearing group (p=.036). Though the fixed and mobile- bearing TAR had both significant hindfoot alignment improvement between the pre-op radiographs and twenty-four months, over time, the fixed-bearing ankle had a significant increase in both the HAV and HAVD (p<.001), suggesting a dynamism of the hindfoot in the fixed-bearing ankle. Conclusion: Correcting coronal and sagittal alignment is important for the long-term survivorship of a TAR. The fixed and mobile-bearing implants had maintained coronal and sagittal alignment in the short term, the temporal course of the fixed-bearing ankle showed an increased in the valgus positioning of the hindfoot.
Specific patterns of H3K79 methylation influence genetic interaction of oncogenes in AML
Authors: Kingsley Molly C. , Xie Hongbo M. , Chen Bo-Rui , Riedel Simone S. , Pastuer Taylor , Bollig Madelyn K. , Shank Tyler , Libbrecht Clara , Stabler Sally P. , Deshpande Aniruddha J. , Intlekofer Andrew M. , Bernt Kathrin M. 
Published: July 2020

Abstract
Understanding mechanisms of cooperation between oncogenes is critical for the development of novel therapies and rational combinations. Acute myeloid leukemia (AML) cells with KMT2A-fusions and KMT2A partial tandem duplications (KMT2APTD) are known to depend on the histone methyltransferase DOT1L, which methylates histone 3 lysine 79 (H3K79). About 30% of KMT2APTD AMLs carry mutations in IDH1/2 (mIDH1/2). Previous studies showed that 2-hydroxyglutarate produced by mIDH1/2 increases H3K79 methylation, and mIDH1/2 patient samples are sensitive to DOT1L inhibition. Together, these findings suggested that stabilization or increases in H3K79 methylation associated with IDH mutations support the proliferation of leukemias dependent on this mark. However, we found that mIDH1/2 and KMT2A alterations failed to cooperate in an experimental model. Instead, mIDH1/2 and 2-hydroxyglutarate exert toxic effects, specifically on KMT2A-rearranged AML cells (fusions/partial tandem duplications). Mechanistically, we uncover an epigenetic barrier to efficient cooperation; mIDH1/2 expression is associated with high global histone 3 lysine 79 dimethylation (H3K79me2) levels, whereas global H3K79me2 is obligate low in KMT2A-rearranged AML. Increasing H3K79me2 levels, specifically in KMT2A-rearrangement leukemias, resulted in transcriptional downregulation of KMT2A target genes and impaired leukemia cell growth. Our study details a complex genetic and epigenetic interaction of 2 classes of oncogenes, IDH1/2 mutations and KMT2A rearrangements, that is unexpected based on the high percentage of IDH mutations in KMT2APTD AML. KMT2A rearrangements are associated with a trend toward lower response rates to mIDH1/2 inhibitors. The substantial adaptation that has to occur for 2 initially counteracting mutations to be tolerated within the same leukemic cell may provide at least a partial explanation for this observation.