bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive Cyber Defense Against Multi-Stage Attacks Using Learning-Based POMDP
Authors: Hu Zhisheng , Zhu Minghui , Liu Peng
Published: November 2020

Growing multi-stage attacks in computer networks impose significant security risks and necessitate the development of effective defense schemes that are able to autonomously respond to intrusions during vulnerability windows. However, the defender faces several real-world challenges, e.g., unknown likelihoods and unknown impacts of successful exploits. In this article, we leverage reinforcement learning to develop an innovative adaptive cyber defense to maximize the cost-effectiveness subject to the aforementioned challenges. In particular, we use Bayesian attack graphs to model the interactions between the attacker and networks. Then we formulate the defense problem of interest as a partially observable Markov decision process problem where the defender maintains belief states to estimate system states, leverages Thompson sampling to estimate transition probabilities, and utilizes reinforcement learning to choose optimal defense actions using measured utility values. The algorithm performance is verified via numerical simulations based on real-world attacks.
Gqα/G11α deficiency in dorsomedial hypothalamus leads to obesity resulting from decreased energy expenditure and impaired sympathetic nerve activity
Authors: Wilson Eric A. , Sun Hui , Cui Zhenzhong , Jahnke Marshal T. , Pandey Mritunjay , Metzger Peter , Gavrilova Oksana , Chen Min , Weinstein Lee S.
Published: November 2020

This paper demonstrates that signaling within the dorsomedial hypothalamus via the G proteins Gqα and G11α, which couple cell surface receptors to the stimulation of phospholipase C, is critical for regulation of energy expenditure, thermoregulation by brown adipose tissue and the induction of white adipose tissue browning.
A Blockchain Prediction Model on Time, Value, and Purchase Based on Markov Chain and Queuing Theory in Stock Trade
Authors: Lian Wenjuan , Fan Qi , Jia Bin , Liang Yongquan
Published: November 2020

With the continuous development of the blockchain, it has brought a subversive impact on the blossom of all fields with its characteristics of decentralization, trust-free, and tampering, especially in the financial field. It is of great significance to research the application of blockchain technology in the financial field. As an important part of the financial market, stock has the crucial influence, and the combination of stock and blockchain is becoming a growing trend. In recent years, many studies have focused on the prediction of the stock value, but they have not fully considered the combination of time, value, and purchase. To solve the above problem, we propose a preemption queuing model for multipriority service objects in the blockchain financial architecture according to different service priority. Meanwhile, a queuing-based resource scheduling model is established by using the Markov chain to find the optimal solution. The method in this paper can greatly improve the efficiency of the system and provide a basis for future scientific research in the healthy and sustainable development of the securities industry.
Experimental and Numerical Investigation on an Integrated Thermal Management System for the Li-Ion Battery Module with Phase Change Material
Authors: Huang Qiqiu , Zhong Zhaoda , Li Xinxi , Zhang Guoqing , Wei Dongyang , Yuan Weizhong , Zhang Jiangyun , Zhou Dequan
Published: November 2020

Lightweight power battery modules with outstanding thermal performance are urgently required given the rapid development of electric vehicles. This study proposes a composite phase change material coupled with forced convection as an integrated thermal management system (ITMS) with the aim to control the temperature’s rising tendency and maintain the temperature distribution uniformly within an appropriate range among the battery modules. The thermal behavior effects of airflow rates on the thermal management system were investigated in detail by combining experiments and numerical simulations. Comparisons were conducted between an air cooling system with an optimum flow rate and the ITMS. Experimental results revealed that the cooling effect of the ITMS was better than that of the forced cooling system at a 3 m/s airflow rate. The maximum temperature in the designed battery module was limited to 63.2°C. The maximum temperature difference was limited to 4.8°C at a 4 C discharge rate. This research indicates that the ITMS is an effective and optimized approach to control and balance the temperature among battery modules, thereby providing engineers with design optimization strategies for similar systems.
Grand Challenges as Educational Innovations in Higher Education: A Scoping Review of the Literature
Authors: Nowell Lorelli , Dhingra Swati , Andrews Kimberley , Gospodinov Julia , Liu Cathy , Alix Hayden K.
Published: November 2020

Grand challenges are complex problems that are common to much of society, affect large populations, and may have several possible solutions. Incorporation of grand challenges into higher education courses can facilitate the development of collaborative problem-solving skills while providing relevant and practical opportunities to experience the dynamics involved in real-world work. Although grand challenges are becoming more commonly used in higher education, to date, there has been no synthesis of how grand challenges are incorporated and the learning outcomes of engaging in grand challenge work. In this scoping review, we examined and mapped the state of evidence for the use of grand challenges in higher education. We conducted the review according to the Johanna Briggs Institute methodology for scoping reviews and considered quantitative, qualitative, and mixed-methods studies as well as literature reviews, program descriptions, and opinion papers published in English without limitations on year of publication. We used a data extraction tool to synthesize and present our findings in a tabular form with accompanying narrative summaries. The results reveal a growing global interest in the use of grand challenges in higher education while highlighting a lack of rigorous empirical evidence on the impact on student learning.
Acceleration Level Control of Redundant Manipulators with Physical Constraints Compliance and Disturbance Rejection under Complex Environment
Authors: Liang Jinglun , Rong Yisheng , Ye Guoliang , Li Xiaoxiao , Guo Jianwen , He Zhenzhen
Published: November 2020

Investigation of joint torque constraint compliance is of significance for robot manipulators especially working in complex environments. A lot of which is attributed to that, on the one hand, it is beneficial to the improvement of both safety and reliability of the mission execution. On the other hand, the energy consumption required by the robot to complete the desired mission can be reduced. Most existing schemes do not take the joint torque limit and other inherent physical structure limits in a manipulator into account at the same time. In addition, many unavoidable uncertainties such as the external environmental disturbance and/or electromagnetism interferences in the circuit system may influence the accuracy and effectiveness of the task execution for a robot. In this study, we cast light on the acceleration level control of redundant robot manipulators considering both four physical constraint limits and interference rejection. A robust unified quadratic-programming-based hybrid control scheme is proposed, where the joint torque constraints are converted as two inequality constraints based on the robots’ dynamics equation. A recurrent-neural-network-based controller is designed for solving the control variable. Numerical experiments performing in PUMA 560 manipulator and planer manipulator illustrate that a rational torque distribution is obtained among the joints and the considered physical structural vectors are all restricted to the respective constraint range. In addition, even disturbed by the noise, the manipulator still successfully tracks the desired trajectory under the proposed control scheme.
Identification and Characterization of a Newly Isolated Chitinase-Producing Strain Bacillus licheniformis SSCL-10 for Chitin Degradation
Authors: Sasi Abirami , Duraipandiyan Nagarajan , Marikani Kannan , Dhanasekaran Sugapriya , Al-Dayan Noura , Venugopal Divya
Published: November 2020

Chitinases or chitinolytic enzymes have different applications in the field of medicine, agriculture, and industry. The present study is aimed at developing an effective hyperchitinase-producing mutant strain of novel Bacillus licheniformis. A simple and rapid methodology was used for screening potential chitinolytic microbiota by chemical mutagenesis with ethylmethane sulfonate and irradiation with UV. There were 16 mutant strains exhibiting chitinase activity. Out of the chitinase-producing strains, the strain with maximum chitinase activity was selected, the protein was partially purified by SDS-PAGE, and the strain was identified as Bacillus licheniformis (SSCL-10) with the highest specific activity of 3.4 U/mL. The induced mutation model has been successfully implemented in the mutant EMS-13 (20.2 U/mL) that produces 5-6-fold higher yield of chitinase, whereas the mutant UV-11 (13.3 U/mL) has 3-4-fold greater chitinase activity compared to the wild strain. The partially purified chitinase has a molecular weight of 66 kDa. The wild strain (SSCL-10) was identified as Bacillus licheniformis using 16S rRNA sequence analysis. This study explores the potential applications of hyperchitinase-producing bacteria in recycling and processing chitin wastes from crustaceans and shrimp, thereby adding value to the crustacean industry.
Macular Microvasculature Density Changes in Anisometropic Amblyopic Eyes after Successful Treatment
Authors: Chen Wuhe , Thorn Frank , Deng Ruzhi , Li Xiaoman , Lou Jiangtao , Wang Yingjie , Yu Xinping
Published: November 2020

Purpose. To determine if the abnormal macular microvasculature in hyperopic anisometropic amblyopia changes after occlusion therapy, and to discover if the macular microvasculature influences the efficacy of amblyopic treatment. Materials and Methods. Twenty-two children with hyperopic anisometropic amblyopia (median, 8 years old) were enrolled along with 66 healthy controls of similar age and gender distribution. Best-corrected visual acuity (BCVA) was determined, and macular vessel density in the superficial and deep capillary plexuses (SCPs and DCPs, respectively) was measured by optical coherence tomography angiography before and after refractive correction and occlusion therapy. Changes in BCVA and macular SCP and DCP vessel density were measured after amblyopia treatment of 7.5 ± 4.4 months. Results. The amblyopic baseline BCVA, logMAR 0.42 ± 0.27, improved to logMAR 0.18 ± 0.18 in 14 patients (64%) after amblyopia treatment (

P
<
0.001

). In 8 patients (36%), there was no improvement in the BCVA. In amblyopic eyes with improved BCVA, the SCP density tended to increase in each parafoveal quadrant, while it tended to decrease in all quadrants of the fellow eyes. For patients in whom BCVA did not improve, the macular SCP vessel density tended to decrease in all quadrants of the amblyopic and fellow eyes. The posttreatment difference in SCP vessel density between amblyopic and fellow eyes was not significant. Multiple linear regression analysis showed that older age and greater foveal SCP vessel density were negatively correlated with BCVA improvement (

P
<
0.018

and

P
<
0.036

, respectively). Conclusions. Macular vessel density tends to increase in anisometropic amblyopic eyes after successful treatment. Younger age and lower SCP macular density are predictive of a greater therapeutic effect of occlusion therapy.
Finite-Time Tracking Control for Nonstrict-Feedback State-Delayed Nonlinear Systems with Full-State Constraints and Unmodeled Dynamics
Authors: Yao Yangang , Tan Jieqing , Wu Jian
Published: November 2020

The problem of finite-time tracking control is discussed for a class of uncertain nonstrict-feedback time-varying state delay nonlinear systems with full-state constraints and unmodeled dynamics. Different from traditional finite-control methods, a

C

1

smooth finite-time adaptive control framework is introduced by employing a smooth switch between the fractional and cubic form state feedback, so that the desired fast finite-time control performance can be guaranteed. By constructing appropriate Lyapunov-Krasovskii functionals, the uncertain terms produced by time-varying state delays are compensated for and unmodeled dynamics is coped with by introducing a dynamical signal. In order to avoid the inherent problem of “complexity of explosion” in the backstepping-design process, the DSC technology with a novel nonlinear filter is introduced to simplify the structure of the controller. Furthermore, the results show that all the internal error signals are driven to converge into small regions in a finite time, and the full-state constraints are not violated. Simulation results verify the effectiveness of the proposed method.
Oncolytic Reovirus (pelareorep) Induces Autophagy in KRAS-mutated Colorectal Cancer
Authors: Jiffry Jeeshan , Thavornwatanayong Thongthai , Rao Devika , Fogel Elisha J. , Saytoo Durvanand , Nahata Rishika , Guzik Hillary , Chaudhary Imran , Augustine Titto , Goel Sanjay , Maitra Radhashree
Published: November 2020

Purpose:

To explore the effects of pelareorep on autophagy in multiple models of colorectal cancer, including patient-derived peripheral blood mononuclear cells (PBMCs).

Experimental Design:

HCT116 [KRAS mutant (mut)] and Hke3 [KRAS wild-type (WT)] cells were treated with pelareorep (multiplicity of infection, 5) and harvested at 6 and 9 hours. LC3 A/B expression was determined by immunofluorescence and flow cytometry; five autophagic proteins were analyzed by Western blotting. The expression of 88 autophagy genes was determined by qRT-PCR. Syngeneic mouse models, CT26/Balb-C (KRAS mut) and MC38/C57B6 (KRAS WT), were developed and treated with pelareorep (10 × 106 plaque-forming unit/day) intraperitoneally. Protein and RNA were extracted from harvested tumor tissues. PBMCs from five experimental and three control patients were sampled at 0 (pre) and 48 hours, and on days 8 and 15. The gene expression normalized to “pre” was determined using 2−ΔΔCt method.

Results:

Pelareorep induced significant upregulation of LC3 A/B in HCT116 as compared with Hke3 cells by immunofluorescence (3.24 × and 8.67 ×), flow cytometry (2.37 × and 2.58 ×), and autophagosome formation (2.02 × and 1.57 ×), at 6 and 9 hours, respectively; all P < 0.05. Western blot analysis showed an increase in LC3 A/B (2.38 × and 6.82 ×) and Beclin1 (1.17 × and 1.24 ×) at 6 and 9 hours, ATG5 (2.4 ×) and P-62 (1.52 ×) at 6 hours, and VPS-34 (1.39 ×) at 9 hours (all P < 0.05). Induction of 13 transcripts in cell lines (>4 ×; 6 and 9 hours; P < 0.05), 12 transcripts in CT26 (qRT-PCR), and 14 transcripts in human PBMCs (P < 0.05) was observed. LC3 A/B, RICTOR, and RASD1 expression was upregulated in all three model systems.

Conclusions:

Pelareorep hijacks host autophagic machinery in KRAS-mut conditions to augment its propagation and preferential oncolysis of the cancer cells.
So-Called Butcher’s Warts Appeared on the Hands of a Meat Handler
Authors: Miyata Kazunori , Go Usho , Mitsuishi Tsuyoshi
Published: November 2020

We present a case of so-called butcher’s warts in a meat handler with atopic dermatitis. PCR with direct sequence analysis confirmed the presence of HPV 7 in the hand warts of the patient. Histopathologically, the lesion contained vacuolated cells with centered nuclei, and there were no abundant keratohyalin granules in the granular layer. Clinically, HPV 7-induced warts tend to appear on the hands of meat/fish handlers or cutters in the world. Therefore, meat/fish had been thought to act as a vector for the transmission of HPV 7. In our case, the Japanese patient’s occupation required the handling of meat/fish products, and HPV 7 was found from his hand warts. This evidence indicated that HPV 7 was widely distributed in the world. However, this patient worked in a Japanese restaurant, which required the handling of meat/fish products with tools such as knives and chopping boards. Therefore, we suggested that HPV 7 might be correlated with specific reservoirs.
Physical Manipulation-Induced Femoral Neck Fracture: A Case Report
Authors: Ayoubi Rami A. , Nassour Nour S. , Saidy Elias G. , Aouad Dany K. , Maalouly Joseph S. , Daou Elie B.
Published: November 2020

Manipulative treatments for pain are very widely used nowadays by a variety of physicians. These treatment modalities are generally safe, but various studies have reported serious complications. This report presents the case of a 78-year-old male patient with a history of Parkinson’s disease, who was diagnosed with a right hip fracture that occurred as a result of physical manipulative treatment. He underwent a cemented hemi-arthroplasty as appropriate surgical treatment of his condition. Manipulative treatments can result in minor and major complications ranging from simple sprains and rib fractures to cerebrovascular accidents and death. The frequency of these events seems to be rare; however, no robust studies are present and further investigations are urgently needed. Hip fractures as a result of this treatment have not been previously mentioned. This is the first reported case in the literature of a hip fracture resulting from manipulative treatment. Primary care physicians and orthopedists should be aware of the possibility of this outcome and rule it out whenever necessary.
Central Nervous System Vasculitis as a Rare Presentation of Mycoplasma pneumoniae: A Case Report
Authors: Ahmed Ashraf Omer Elamin , Babikir Mona Mohammad Ibraheem , Khojali Amir Elssoni Mahjoup , Arachchige Suresh Nalaka Menik , Abdirahman Abdirahman Mohamud , Mohamed Mouhand Faisal Hamad
Published: November 2020

Mycobacteria pneumoniae (MP) commonly causes upper and lower respiratory tract infections. The clinical manifestation is classified as pulmonary and extrapulmonary. These manifestations vary according to the involved system. MP may affect one system or more at a time. Commonly prodromal respiratory symptoms precede systemic involvement. Central nervous system involvement in uncommon. This report is presenting a rare case of central nervous system vasculitis secondary to MP, highlighting the diagnosis and management with a succinct literature review.
Impact of a Stay-at-Home Order on Stroke Admission, Subtype, and Metrics during the COVID-19 Pandemic
Authors: Rameez Fnu , McCarthy Philip , Cheng Yao , Packard Laurel M. , Davis Alan T. , Wees Nabil , Khan Nadeem , Singer Justin , Khan Muhib , Min Jiangyong
Published: November 2020

Objective: Our study aims to evaluate the impact of a stay-at-home order on stroke metrics during the 2019-novel coronavirus (COVID-19) pandemic. Methods: Data on baseline characteristics, stroke subtype, initial National Institutes of Health Stroke Scale (NIHSS) score, the time between last known well (LKW) to emergency department (ED) arrival, tissue plasminogen activator (tPA) administration, the involvement of large vessel occlusion (LVO), and whether mechanical thrombectomy (MT) was pursued in patients with acute stroke were extracted from 24 March to 23 April 2020 (the time period of a stay-at-home order was placed due to the COVID-19 pandemic as the study group) at a tertiary care hospital in West Michigan, USA, compared with data from 24 March to 23 April 2019 (control group). Results: Our study demonstrated a reduction in cases of acute ischemic stroke (AIS), although this did not reach statistical significance. However, there was an increase in hemorrhagic stroke (7.5% controls vs. 19.2% study group). The age of stroke patients was significantly younger during the period of the stay-at-home order compared to the control group. We identified a significant overall delay of ED arrivals from LKW in the study group. Additionally, an increased number of AIS patients with LVO in the study group (34.8%) was found compared to the control group (17.5%). A significantly increased number of patients received MT in the study group. Additionally, 11 patients were COVID-19 PCR-positive in the study group, 10 with AIS and only 1 with hemorrhagic stroke. Patients with COVID-19 had a high incidence of atrial fibrillation and hyperlipidemia. One AIS patient with COVID-19 rapidly developed cytotoxic edema with corresponding elevated inflammatory biomarkers. No statistical significance was noted when stroke subtype, LVO, and MT groups were compared. Conclusions: There was a trend of decreasing AIS admissions during the COVID-19 pandemic. There was also a significantly increased number of AIS patients with LVO who received MT, especially those with COVID-19. We conclude that cytokine storm resulting from SARS-CoV-2 infection might play a role in AIS patients with COVID-19.
Abstract 106: Covid-19 Pandemic Impact on Ems Runs and Resuscitation Attempts
Authors: Asmar Timothy , Snider John , Dunne Robert B , Feld Michael , Miller Joseph B , Klausner Howard
Published: November 2020

Background:
The frequency of EMS runs, resuscitation attempts, & out of hospital cardiac arrest survival within a pandemic period has not been studied within the Detroit and metro Detroit region in Michigan. To analyze and study the consequences associated with the spread of COVID-19 within two Michigan counties, a retrospective review from two different medical control authorities (MCA) was completed. We hypothesized the number of out of hospital cardiac arrests and EMS runs to increase during the COVID-19 pandemic, while resuscitation attempts to decrease.

Methods:
This is a retrospective review study. Records from two MCAs, the Detroit East Medical Control Authority (DEMCA) and the Macomb County Medical Control Authority (MCMCA), were utilized and data was extracted and extrapolated. Each of these MCAs oversee Emergency Medical Services (EMS) within their respective counties. DEMCA provides coverage for the eastern region of Wayne County and MCMCA serves all of Macomb County. Runs, dead-on-scene numbers, & resuscitation attempts were each assessed from March through May of 2019 & 2020.

Results:
There were nearly double the number of EMS runs for out of hospital cardiac arrest during the 3 main months of the pandemic. In March through May 2020 there were 1756 runs with a mean age of 62.7 years vs. 988 runs during the same period in 2020 with a higher mean age of 65.1 years (p<0.01). This difference was most pronounced in April, which was the height of the pandemic in Michigan (782 vs. 312). The higher number of EMS runs was also more pronounced in Wayne county (1.86 times 2019 numbers) compared to Macomb County (1.65 times 2019 numbers). Resuscitation was attempted on 566 (32.2%) during the pandemic compared to 222 (22.5%) during the same period in the prior year (OR 0.61, 95% CI 0.51 - 0.73, p<0.01). The proportion of patients transferred from the field to an ED did not change significantly (2.6% in the control period vs. 2.1% during the pandemic, p=0.325).

Conclusion:
There was a 1.78 fold rise in out of hospital cardiac arrest EMS runs during the peak months of the pandemic in metro Detroit compared to the same period in 2019. Despite national concerns on the safety of resuscitation with Covid-19, a higher proportion of patients had resuscitation attempted during the pandemic.
Abstract 110: Introduction of a Mechanical Chest Compression Device for In-hospital Cardiac Arrest During the Covid-19 Pandemic
Authors: Bhatnagar Anish , Lee Jennifer , Khraishah Haitham , Hsu Douglas , Hayes Margaret , Moskowitz Ari
Published: November 2020

Introduction:
Cardiopulmonary resuscitation (CPR) for hospitalized patients during the COVID-19 pandemic presents unique challenges to resuscitation teams, including a potentially increased risk from virus aerosolization. As such, the American Heart Association has published guidance, which includes a suggested use of mechanical chest compression devices if available. We herein describe the experience at a tertiary care hospital with a high COVID-19 case load, where mechanical compression devices were rapidly deployed early in the pandemic.

Methods:
In April 2020, two LUCAS® chest compression systems were deployed and staff trained in their use. In June 2020, an electronic survey was developed that explored experiences of resuscitation providers who responded to in-hospital cardiac arrests (IHCA) during the pandemic. The survey was sent to the physician code leaders, anesthesiologists, and intensive care nurses who had responded to IHCAs.

Results:
Forty-four (58%) of 76 surveys were returned. There were 21 IHCAs during the study period. Of the respondents, 15 (34%) were nurses and 14 (31.8%) were medical trainees. Thirty-two (73%) respondents had been involved in an IHCA where the LUCAS® was deployed. Ten (31.3%) respondents agreed/strongly agreed that transferring to the LUCAS® backboard was difficult, and that it was difficult to latch the LUCAS® to the backboard. Twelve (37.5%) respondents believed that the LUCAS resulted in delays in care. Twenty-two (68.8%) respondents thought that LUCAS® resulted in a more controlled resuscitation experience, 20 (62.5%) felt the LUCAS® improved the quality of chest compressions, and 23 (71.9%) reported that the LUCAS® allowed for fewer people in the room. Those who responded to arrests where the LUCAS® was not deployed, reported patient size and difficulty attaching the device as common obstacles.

Conclusions:
Rapid deployment of mechanical chest compression devices during the COVID-19 pandemic is feasible. Although there are substantial technical challenges, most report a more controlled resuscitation experience, better compression quality, and fewer individuals in the room. Additional staff training may be necessary to achieve optimal results.
Abstract 112: Short- and Long-term Survival of Patients Supported on Venoarterial and Veno-venous Extracorporeal Membrane Oxygenation
Authors: Florea Ioana , Kotkar Kunal , Damiano Ralph , Moon Marc R , Itoh Akinobu , Masood Muhammad
Published: November 2020

Introduction:
Use of both venoarterial (VA) and veno-venous (VV) extracorporeal membrane oxygenation (ECMO) has broadened to an expanded set of indications for supporting patients in shock, but outcome data by these indications remains limited. This study examines survival of VA and VV ECMO patients by indication.

Methods:
A retrospective review of adults supported by ECMO at a single center for cardiogenic shock between January 2010 - November 2018 was conducted. VA ECMO patients (n=449) and VV ECMO patients (n=91) were classified according to indication for ECMO support. Kaplan-Meier analysis was used to construct survival curves at 30 days and 1 year and compared using log-rank test. Post-hoc Tukey test was used to adjust for multiple comparisons.

Results:
The subgroups of indication for VA-ECMO support were Acute Pulmonary Embolism (PE, n=14), Ischemic Cardiomyopathy or Myocardial Infarction (ICM or MI, n=108), Non-Ischemic Cardiomyopathy (NICM, n=82), Post-Cardiotomy (n=129), Transplant (Tx, n=32), and Other (n=84). Kaplan-Meier estimates of survival stratified by indication at 30 days and 1 year were significant (30d: p=0.006, 1y: p=0.009, Figure 1). Multiple comparisons at 30 days and 1 year were significant for Acute PE v Post-Cardiotomy (30d: p=0.044, 1y: p=0.029), NICM v Post-Cardiotomy (30d: p=0.016, 1y: p=0.025), and Tx v Post-Cardiotomy (30d: p=0.01, 1y: p=0.022). Among VV-ECMO patients, the subgroups of indication were ARDS: Influenza (n=25), ARDS: Other Infection (n=24), and ARDS: Non-Infectious (n=42). No statistically significant difference in survival was appreciated between these indications either at 30 days (p=0.742) or 1 year (p=7.82).

Conclusions:
Patients who require Post-Cardiotomy VA-ECMO support have worse short- and long-term survival compared to patients who require support for Acute PE, NICM, or Transplant indications. Among VV-ECMO patients, however, no survival difference is appreciated by indication.
Abstract 117: Critical Care Management, Hospital Case Volume, and Survival After Extracorporeal Cardiopulmonary Resuscitation
Authors: Tonna Joseph , Selzman Craig , Bartos Jason , Presson Angela , Jo Yeonjung , Becker Lance B , Youngquist Scott T , Thiagarajan Ravi R , Johnson Austin , Rycus Peter , Keenan Heather
Published: November 2020

Introduction:
For patients who receive extracorporeal cardiopulmonary resuscitation (ECPR), the relationship between post-resuscitation management and survival is unknown. Additionally, it is not known if management varies between centers, and if this variation and hospital case volume, are associated with survival.

Hypothesis:
There is center level variability in post-resuscitation management for ECPR patients. This variability, and hospital annual case volume, are associated with survival.

Methods:
We performed an observational study of 4,296 adults who received ECPR from the Extracorporeal Life Support Organization registry from 2014 until 2019. We examined clinical variables within the first 24 hours after arrest, and hospital annual ECPR volume. The primary outcome was case-mix adjusted survival at hospital discharge, adjusting for factors previously associated with survival after cardiac arrest or extracorporeal membrane oxygenation (ECMO). Mixed effects regression models were used to account for clustering of outcomes by center. Case volume was stratified into low (<6 cases/year), medium (6-12 cases/year) and high (>12 cases/year).

Results:
Patient-level clinical variables after cardiac arrest, varied widely across individual hospitals, including the use of percutaneous coronary intervention (PCI), mechanical venting of the left ventricle, and the use of inotropic medications. Increased ECMO circuit blood flow at 4 hours was associated with survival (OR 1.14 per liter per minute of flow [95% CI 1.04 to 1.24];p=0.004). After 24 hours of ECMO, increased arterial pulsatility (OR 1.44 [95% CI 1.32 to 1.58]; p<0.001), the placement of a distal perfusion catheter (OR 1.79 [95% CI 1.19 to 2.67]; p=0.005), and the placement of a mechanical left ventricular vent (OR 1.37 [95% CI 1.07 to 1.76]; p=0.012) were all significantly associated with survival. There was a nonsignificant association of the use of PCI after ECMO cannulation with survival (OR 1.31 [95% CI 0.998 to 1.91]; p=0.051). High case volume was not associated with survival (OR 1.32 [95% CI 0.98 to 1.78];p=0.072).

Conclusions:
Clinical management of ECPR patients varies across hospitals. These clinical variables and therapies are associated with survival, however center volume is not.
Abstract 135: Telephone-assisted Cardiopulmonary Resuscitation May Overcome Ethnic and Age Variation Observed in Bystander CPR
Authors: Blewer Audrey L , Shahidah Binte Ahmad Nur , Leong Benjamin Sieu-Hon , Pek Pin Pin , Ng Yih Yng , Joiner Anjni , Arulanandam Shalini , Ong Marcus E
Published: November 2020

Introduction:
Ethnicity, female gender, and older age are associated with lower rates of receipt of bystander cardiopulmonary resuscitation (B-CPR). Increasing telephone-assisted CPR (T-CPR), or provision of CPR instructions when individuals call 9-1-1, may improve B-CPR rates. It is unknown whether provision of T-CPR may overcome ethnic, gender and age variation seen in B-CPR.

Objectives:
We sought to assess whether provision of T-CPR may overcome ethnic, gender, and age variation seen in B-CPR. We hypothesized that the provision of T-CPR will improve B-CPR and reduce differences associated with ethnicity.

Methods:
We conducted a retrospective study of adult, non-traumatic out-of-hospital cardiac arrests (OHCA) from the Singapore registry (4/2010-12/2016). We assessed variation in B-CPR by ethnicity, female gender, and increased older age, stratified by receipt of T-CPR. We examined the differences using descriptive statistics and multivariable logistic regression accounting for confounding.

Results:
From 2010-2016, the Singapore registry contained 12,546 OHCA events. Excluding traumatic, EMS witnessed, and healthcare facility arrests, 7,997 events were analyzed. Of these, mean age was 66±19 and 65% were male. B-CPR was administered in 53% of the events, while T-CPR was provided in 30% of the events. In a univariate analysis, female gender was associated with variation in B-CPR if T-CPR was not provided (F: 29% vs M: 35%, p<0.01) and provision of T-CPR reduced this variation (p=0.17), but this association was not observed in the multivariable logistic regression. When adjusting for confounding, ethnicity was associated with variation in B-CPR if T-CPR was not provided (p<0.01), while provision of T-CPR reduced this variation (p=0.50). Additionally, increased older age was associated with a decreased likelihood of receipt of B-CPR if T-CPR was not provided (OR: 0.99 (0.98-0.99), p<0.01), while this variation was not observed with provision of T-CPR (p=0.50).

Conclusion:
T-CPR modified the known B-CPR differences seen in ethnicity and increased older age, but did not modify differences seen in gender when controlling for other covariates. These findings may help inform public policy and methods to decrease variation and increase B-CPR.
Abstract 142: Combined Therapy with Polyethylene Glycol-20k and MCC950 Preserves Post-resuscitation Myocardial Mitochondrial Function in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation
Authors: Liang Lian , Zhang Guozhen , Li Hui , Cheng Cheng , Jin Tao , Su Chengli , xiao yan , Bradley Jennifer , Fyffe-Freil Ria , Peberdy Mary Ann A , Ornato Joseph P , Mangino Martin , Tang Wanchun
Published: November 2020

Introduction:
Mitochondrial dysfunction from global ischemic-reperfusion (I/R) injury is a major contributor to post-resuscitation myocardial dysfunction. Polyethylene Glycol-20k (PEG-20k) shortens the no-flow phenomenon and improves microcirculation while MCC950 selectively inhibits activation of the NLRP3-inflammasome ensuing pyroptosis. We evaluated the effect of combined therapy with PEG-20k and MCC950 on myocardial mitochondrial function as measured by electron transport chain complex respiration in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR).

Methods:
30 Sprague-Dawley rats weighing between 450-550 g were randomized into five groups (n=6): (1) sham (S); (2) control (C); (3) PEG-20k (P); (4) MCC950 (M); (5) combined (P&M). Ventricular fibrillation (VF) was electrically induced and untreated for 6min, followed by 8min CPR. Resuscitation was attempted with a 4J defibrillation. 2mL P was infused over 2 min at the beginning of CPR, while M (10mg/kg) was administered intraperitoneal (IP) immediately after return of spontaneous circulation (ROSC). At ROSC 6hr, 100mg of heart was harvested, transferred directly into ice-cold K medium (1mL), and homogenized to obtain a 10% homogenate. Homogenates (50μL) were transferred to calibrated Oxygraph-2 chambers. Mitochondrial function was measured using high resolution respirometry. Oxygen flux was corrected and expressed by tissue wet weight, pmol/(min*mg). Data were analyzed by one-way analysis of variance (one-way ANOVA) followed by Tukey’s post hoc test for comparisons between multiple groups.

Results:
Complex I respiration in C was compromised at ROSC 6hr compared to S (564.0±160.0 vs 2729.5±339.5, p<0.001). As expected, P and M restored complex I respiration (1224.4±328.6, p<0.001) and (1804.4±293.1, p<0.01) compared to C. P&M further consolidated Complex I respiration function recovery (2527.6±145.5).

Conclusion:
Combined Therapy with PEG-20k and MCC950 preserves post-resuscitation myocardial mitochondrial function in a rat model of CA and CPR.
Abstract 145: High Mobility Group Box 1 (HMGB1) is a Major Mediator of the Post-cardiac Arrest Syndrome
Authors: Boissady Emilie , El Hedjaj Cynthia , Kohlhauer Matthias , Lidouren Fanny , Ghaleh Bijan , Tissier Renaud
Published: November 2020

Introduction:
Profound immune disorders are triggered by cell death and subsequent release of danger signals after cardiac arrest (CA).

Hypothesis:
High mobility group box-1 (HMGB1) is one of the main endogenous mediators released by ischemic cell death. Our goal was to determine whether its inhibition could provide neuroprotection and improve the outcome after experimental CA.

Methods:
After 10 min of ventricular fibrillation and resuscitation, rabbits either received an administration of saline (CT group, n=10) or glycyrrhizin (GL group, n=10), a direct inhibitor of HMGB1 (4 mg/kg, i.v.). Animals were followed during 3 days after CA to evaluate the neurological dysfunction. Additional animals were submitted to the same protocol with brain withdrawal 2 or 6 h after CA for immune cell count by cytometry.

Results:
After CA, HMGB1 blood levels was significantly reduced in CT vs GL group (30±7 vs 17±2 ng/ml at t=30 min after CA). The systemic inflammatory response was subsequently attenuated in GL vs CT, as shown by reduced interleukin-6 concentration (231±34 vs 993±331 pg/ml at 180 min, respectively). In the CT group, a rapid accumulation of neutrophils (CD11b+) and T cells (CD3+, CD4+ and CD8+) was also evidenced in the brain after cardiac arrest. GL specifically reduced the influx of T cells (e.g., 2.7±0.3 vs 7.3±2.6% of CD3+ cells in the brain at 6 h after CA in GL vs CT, respectively) without modifying neutrophils counts. This effect was neither related to differences in blood cells counts nor a modification of blood-brain-barrier permeability between groups, which then suggests a specific inhibition of cerebral chemo-attraction of T cells by glycyrrhizin. Those modifications were ultimately associated with a reduction in neuronal cell death (fluorojade C staining), as well as improved neurological recovery in GL vs CT groups (mean neurological dysfunction scores at day 3 = 58±13 vs 100±0 %, respectively).

Conclusion:
HMGB1 is a major mediator of the cerebral early infiltration by T cells following CA. Its inhibition by glycyrrhizin could be a relevant therapeutic target to prevent the propagation of neurological damages.
Abstract 150: Effect of Amplitude Spectral Area on Termination of Fibrillation and Outcomes in Pediatric Cardiac Arrest
Authors: Raymond Tia , Pandit Sandeep , Griffis Heather M , Zhang Xuemei , Hanna Richard , Niles Dana E , Silver Annemarie E , Lasa Javier J , Haskell Sarah E , Atkins Dianne L , Nadkarni Vinay M
Published: November 2020

Introduction:
Amplitude spectral area (AMSA) predicts termination of fibrillation (TOF) with return of spontaneous circulation (ROSC) and hospital survival in adults, but has not been studied during pediatric cardiac arrest (pCA).

Hypothesis:
We characterized AMSA during pCA from a pediatric resuscitation quality (pediRES-Q) collaborative and hypothesized that AMSA would be associated with TOF and ROSC.

Methods:
Children <18 years of age with pCA and VF were studied. AMSA was measured for 2 seconds prior to each shock and also averaged for each subject (AMSA-avg). TOF was defined as termination of VF 10 secs after defibrillation (DF) to any rhythm other than VF. ROSC was defined as >20 mins without chest compressions. Univariate and multivariable logistic regression analyses controlling for weight, current, and illness category (cardiac vs non-cardiac) were performed. Primary endpoints were TOF and ROSC without ECMO. Secondary endpoints were 24-hr survival and survival to hospital discharge.

Results:
Between 2015-2019, 50 children from 14 hospitals (median age 3.7 years [IQR 0.6, 13.1]; median weight 16.3 kgs [IQR 6.9, 37.2]; 46% male; 73% cardiac illness category) were identified. IHCA occurred in 47 children and OHCA in 3 children. We analyzed 111 shocks with median number of DFs 1.0 [IQR 1.0, 3.0], median DF energy dose 3.27 J/kg [IQR 2.65,5.01], median DF current 0.64 A/kg [IQR 0.38,0.96], median AMSA 12.21 [IQR 7.17,17.03], and median AMSA-avg 14.6 [IQR 8.6,19.2]. TOF was achieved in 72 DFs (65%), ROSC without ECMO in 31 (62%), ROC with ECMO in 11 (22%), 24-hr survival in 40 (80%), and survival to hospital discharge in 26 (52%). Weight (OR 0.91 [0.84, 0.99] P=0.025) and DF current (OR 1.44 [0.97, 2.2] P=0.07), but not AMSA, were significantly associated with TOF for the first shock. Controlling for DF current and illness category, there was a significant association between AMSA-avg (OR 1.11 [1.0, 1.24] P=0.044) and ROSC without ECMO. There was no significant association between AMSA-avg and 24-hr survival or survival to hospital discharge.

Conclusions:
In pediatric patients, TOF was associated with weight and DF current, but not AMSA, whereas AMSA-avg was associated with ROSC without ECMO, but not 24-hr survival or survival to hospital discharge.
Abstract 204: Association Between Presence of Advanced Airway and Hyperventilation During Pediatric Cardiopulmonary Resuscitation: A Report from the VIPER Collaborative
Authors: OConnell Karen , Myers Sage , Kerrey Benjamin , Sandler Alexis , Keane Ryan , Parrish Benjamin , Watanabe Ichiro , Donoghue Aaron
Published: November 2020

Background:
Hyperventilation is common during pediatric CPR and has known deleterious hemodynamic consequences. It is not known whether the presence of an advanced airway (AA) is independently associated with hyperventilation.

Objective:
To determine the independent association between the presence of an AA and hyperventilation during pediatric CPR in a collaborative of pediatric emergency departments using video review during resuscitations.

Methods/Design:
We present a report from the Videography in Pediatric Emergency Resuscitation (VIPER) Collaborative, a prospective review database. All events where CPR was performed and manual ventilations could be counted for at least 30 seconds were eligible for inclusion. Ventilation rates were counted and expressed in segments corresponding to individual CPR providers (‘compressor segments') and extrapolated to breaths per minute (bpm) where applicable. Hyperventilation was defined as a rate greater than 12 bpm, in accordance with American Heart Association recommendations. Ventilation rates were compared between CPR segments with a natural airway (bag-valve mask device; NA) versus an advanced airway (endotracheal tube or supraglottic airway; AA). Univariate analysis was done by two sided t-testing. Repeated measures logistic regression with random effects modeling (patient as intercept) was performed to determine the independent association of the presence of an AA with hyperventilation.

Results/Discussion:
595 compressor segments in 67 CPR events were analyzed. Twenty-six patients underwent intubation and had segments with both NA and AA analyzed. Across all patients, 402/595 (68%) of segments occurred with an AA. Ventilation rates were significantly higher in patients with an AA compared with NA (14 + 10 bpm vs. 24 + 17 bpm, p < 0.001). By multivariate analysis, the presence of an advanced airway was independently associated with hyperventilation (AOR 12.2, 95% CI 5.0 - 30.3) during pediatric CPR. Future studies should examine methods of limiting manual hyperventilation during pediatric CPR, as well as the impact of ventilation rates on patient outcomes.
Abstract 211: UAMC-3203 Reduces the Severity of Post-resuscitation Myocardial Dysfunction in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation
Authors: Jin Tao , Cheng Cheng , Li Hui , Liang Lian , Zhang Guozhen , Bradley Jennifer , Peberdy Mary Ann A , Ornato Joseph P , Tang Wanchun
Published: November 2020

Introduction:
Previous studies have demonstrated that ferroptosis, a newly defined iron-dependent cell death, mediates ischemia/reperfusion induced cardiomyopathy. However, it is unclear whether ferroptosis plays a role in post-resuscitation myocardial dysfunction (PRMD). This study investigated the effects of UAMC-3203, a novel analog of ferroptosis specific inhibitors, on myocardial function after cardiopulmonary resuscitation (CPR).

Hypothesis:
Administration of UAMC-3203 during CPR alleviates PRMD in a rat model of cardiac arrest (CA) and CPR.

Methods:
18 male Sprague-Dawley rats weighing between 450-550g were randomized into 3 groups: 1) Sham, 2) Control, and 3) UAMC-3203 (5mg/kg, IP at start of precordial compression). Ventricular fibrillation (VF) was induced and continued for 6min. CPR was then initiated for 8min, after which defibrillation was attempted. Ejection fraction (EF), cardiac output (CO) and myocardial performance index (MPI) were measured by echocardiography at baseline, 15min, 1h, 3h and 6h respectively after return of spontaneous circulation (ROSC).

Results:
A significant reduction in cardiac function was observed after resuscitation. At 15 minutes after ROSC, ultrasound showed no difference in cardiac function between UAMC and control. However, at 1, 3, and 6 h after ROSC, UAMC significantly improved myocardial function (p<0.05) (Fig. 1).

Conclusion:
A ferroptosis-specific inhibitor, UAMC-3203, alleviated PRMD significantly in a rat of model of CA and CPR. Further study is needed to determine the benefit of this agent in larger animals and potential safety in humans before it can be tested in clinical resuscitation.
Abstract 213: Disruption of Mitochondrial Cristae Integrity in Lethal Myocardial Ischemia-Reperfusion Injury: Association or Cause-and-Effect?
Authors: Kulek Andrew R , Undyala Vishnu V.R. , Raghunayakula Sarita , Sanderson Thomas H , Przyklenk Karin
Published: November 2020

Background:
Considerable attention has focused on the concept that disruption of mitochondrial structure/function is a determinant of cell death in cardiomyocytes subjected to ischemia-reperfusion (IR). However, the details of this relationship, and the precise mitochondrial event(s) that precipitate lethal IR injury, remain unresolved.

Aim:
Emerging evidence has revealed that cardiomyocytes subjected to IR display: i) degradation of optic atrophy protein-1 (OPA1), the inner mitochondrial membrane protein responsible for maintaining cristae junction integrity, followed by ii) inappropriate release of OPA1 into the cytosol. Accordingly, our goal was to establish whether degradation of OPA1 plays a causal, mechanistic role in determining cardiomyocyte fate.

Methods and Results:
In
Protocol 1
, HL-1 cardiomyocytes underwent 2.5 hrs of simulated ischemia. This was preceded by either a classic intervention known to attenuate IR injury (ischemic preconditioning: IPC) or a matched control period. Cell viability was quantified at 24 hrs post-R, and release of OPA1 into the cytosol was measured at 30 min post-R. In Controls, IR resulted in ~50% cell death and a >15-fold increase in OPA1 in the cytosol - effects that were both attenuated by IPC (Figure: top). In
Protocol 2
: to discern whether these data reflect an
association
between OPA1 degradation and cell death or
cause-and-effect
, HL-1 cells were transfected with either siRNA targeting OPA1 (resulting in near-total knockdown of OPA1 expression: data not shown) or scrambled siRNA. Cardiomyocytes then underwent IPC/no intervention and IR as in Protocol 1. If OPA1 disruption contributes to IR injury, we reasoned that OPA1 knockdown would exacerbate cell death in Controls and attenuate IPC-mediated protection. However, OPA1 knockdown had no effect on cell death in either cohort (Figure: bottom).

Conclusion:
Disruption of OPA1 and loss of cristae junction integrity does not play a causal role in lethal IR injury.