Mortality Cases of Mushroom Poisoning with Russula subnigricans.

Mushroom poisoning is increasing worldwide, as well as the incidence of fatal mushroom poisoning. Several new syndromes associated with mushroom poisoning have been described in the literature. Notably, 1 of the newly identified mushroom poisonings is Russula subnigricans poisoning. R subnigricans can be classified as causing a delayed-onset rhabdomyolytic syndrome as patients with this severe poisoning present with severe rhabdomyolysis, acute kidney injury, and cardiomyopathy. However, there are only a few reports on the toxicity of R subnigricans. We recently treated 6 patients with R subnigricans mushroom poisoning, of whom 2 died. The 2 patients showed severe rhabdomyolysis, metabolic acidosis, acute renal failure, electrolyte imbalance, and irreversible shock, which caused their deaths. Mushroom poisoning should be considered in the evaluation of rhabdomyolysis of unknown origin. In addition, in cases of mushroom poisoning with severe rhabdomyolysis, R subnigricans poisoning should be promptly identified.

Comparison of blood flow between two mechanical compression devices using ultrasound: Animal trial.

BACKGROUND: During manual chest compression, maintaining accurate compression depth and consistency is a challenge. Therefore, mechanical chest compression devices(mCCDs) have been increasingly incorporated in clinical practice. Evaluation and comparison of the efficacy of these devices is critical for extensive clinical application. Hence, this study compared the cardiopulmonary resuscitation(CPR) efficiency of two chest compression devices, LUCAS™ 3(Physio-Control, Redmond, USA) and Easy Pulse (Schiller Medizintechnik GMBH, Feldkirchen, Germany), in terms of blood flow using ultrasonography(USG) in a swine model. METHODS: A swine model was used to compare two mCCDs, LUCAS™ 3 and Easy Pulse. Cardiac arrest was induced by injecting potassium chloride(KCl) solution in eight male mongrel pigs and the animals were randomly divided into two groups. Mechanical CPR was provided to two groups using LUCAS™ 3(LUCAS™ 3 group) and Easy Pulse(Easy Pulse group). USG was used to measure hemodynamic parameters including femoral peak systolic velocity(PSV) and femoral artery diameters(diameter during systole and diastole). Blood flow rate was calculated by multiplying the PSV and cross-sectional area of the femoral artery during systole. The end-tidal carbon dioxide(EtCo2), chest compression depth was measured. Systolic blood pressure, mean blood pressure, and diastolic blood pressure were also measured using an arterial catheter. RESULTS: The chest compression depth was much deeper in LUCAS™ 3 group than Easy Pulse group(LUCAS™ 3: 6.80 cm; Easy Pulse: 3.279 cm, p < 0.001). However, EtCo2 was lower in the LUCAS™ 3 group(LUCAS™ 3: 19.8 mmHg; Easy Pulse: 33.4 mmHg, p < 0.001). The PSV was higher in the LUCAS™ 3 group(LUCAS™ 3: 67.6 cm s-1; Easy Pulse: 55.0 cm s-1, p < 0.001), while the systolic(LUCAS™ 3: 1.5 cm; Easy Pulse: 2.0 cm, p < 0.001) and diastolic diameters were larger in the Easy Pulse group(LUCAS™ 3: 0.4; Easy Pulse: 0.8 cm, p < 0.001). The femoral flood flow rate was also lower in the LUCAS™ 3 group(LUCAS™ 3: 32.55 cm3/s; Easy Pulse: 61.35 cm3/s, p < 0.001). CONCLUSION: The Easy Pulse had a shallower compression depth and slower PSV but had a wider systolic diameter in the femoral artery as compared to that in LUCAS™ 3. Blood flow and EtCo2 were higher in the easy pulse group probably because of the wider diameter. Therefore, an easy pulse may create and maintain more effective intrathoracic pressure.

Russula subnigricans Poisoning Causes Severe Rhabdomyolysis That Could be Misdiagnosed as Non-ST Segment Elevation Myocardial Infarction.

Mushroom poisoning and subsequently the number of patients visiting emergency rooms are increasing, as well as the proportion of fatal mushroom poisonings. Myocytic mushroom poisoning is one of the new clinical classifications. This report documents the course of a family with Russula subnigricans poisoning complicated by severe rhabdomyolysis, including a case that was misdiagnosed as myocardial infarction. A 64-y-old man visited our hospital with symptoms including substernal chest discomfort, nausea, vomiting, and myalgia, lasting for 12 h. His laboratory tests showed elevated serum high-sensitive troponin I. He was diagnosed with non-ST segment elevation myocardial infarction. After that, 2 family members who ate mushrooms together were transferred from a local emergency room with the diagnosis of rhabdomyolysis. Consequently, rhabdomyolysis due to mushroom poisoning was diagnosed. They were hospitalized in the intensive care unit. After admission, conservative management, including primary fluid resuscitation, was performed, and the patients were discharged without complications. R subnigricans poisoning was revealed after investigation and should be considered in mushroom poisoning with rhabdomyolysis. Early recognition and intensive supportive care are important for mushroom poisoning patients.

The Comparison of Emergency Medical Service Responses to and Outcomes of Out-of-hospital Cardiac Arrest before and during the COVID-19 Pandemic in an Area of Korea.

BACKGROUND: Since the declaration of the coronavirus disease 2019 (COVID-19) pandemic, COVID-19 has affected the responses of emergency medical service (EMS) systems to cases of out-of-hospital cardiac arrest (OHCA). The purpose of this study was to identify the impact of the COVID-19 pandemic on EMS responses to and outcomes of adult OHCA in an area of South Korea. METHODS: This was a retrospective observational study of adult OHCA patients attended by EMS providers comparing the EMS responses to and outcomes of adult OHCA during the COVID-19 pandemic to those during the pre-COVID-19 period. Propensity score matching was used to compare the survival rates, and logistic regression analysis was used to assess the impact of the COVID-19 pandemic on the survival of OHCA patients. RESULTS: A total of 891 patients in the pre-COVID-19 group and 1,063 patients in the COVID-19 group were included in the final analysis. During the COVID-19 period, the EMS call time was shifted to a later time period (16:00-24:00, P < 0.001), and the presence of an initial shockable rhythm was increased (pre-COVID-19 vs. COVID-19, 7.97% vs. 11.95%, P = 0.004). The number of tracheal intubations decreased (5.27% vs. 1.22%, P < 0.001), and the use of mechanical chest compression devices (30.53% vs. 44.59%, P < 0.001) and EMS response time (median [quartile 1-quartile 3], 7 [5-10] vs. 8 [6-11], P < 0.001) increased. After propensity score matching, the survival at admission rate (22.52% vs. 18.24%, P = 0.025), survival to discharge rate (7.77% vs. 5.52%, P = 0.056), and favorable neurological outcome (5.97% vs. 3.49%, P < 0.001) decreased. In the propensity score matching analysis of the impact of COVID-19, odds ratios of 0.768 (95% confidence interval [CI], 0.592-0.995) for survival at admission and 0.693 (95% CI, 0.446-1.077) for survival to discharge were found. CONCLUSION: During the COVID-19 period, there were significant changes in the EMS responses to OHCA. These changes are considered to be partly due to social distancing measures. As a result, the proportion of patients with an initial shockable rhythm in the COVID-19 period was greater than that in the pre-COVID-19 period, but the final survival rate and favorable neurological outcome were lower.

Pre-hospital modified shock index for prediction of massive transfusion and mortality in trauma patients.

BACKGROUND: Modified shock index (MSI) is a useful predictor in trauma patients. However, the value of prehospital MSI (preMSI) in trauma patients is unknown. The aim of this study was to investigate the accuracy of preMSI in predicting massive transfusion (MT) and hospital mortality among trauma patients. METHODS: This was a retrospective, observational, single-center study. Patients presenting consecutively to the trauma center between January 2016 and December 2017, were included. The predictive ability of both prehospital shock index (preSI) and preMSI for MT and hospital mortality was assessed by calculating the areas under the receiver operating characteristic curves (AUROCs). RESULTS: A total of 1007 patients were included. Seventy-eight (7.7%) patients received MT, and 30 (3.0%) patients died within 24 h of admission to the trauma center. The AUROCs for predicting MT with preSI and preMSI were 0.773 (95% confidence interval [CI], 0.746-0.798) and 0.765 (95% CI, 0.738-0.791), respectively. The AUROCs for predicting 24-hour mortality with preSI and preMSI were 0.584 (95% CI, 0.553-0.615) and 0.581 (95% CI, 0.550-0.612), respectively. CONCLUSIONS: PreSI and preMSI showed moderate accuracy in predicting MT. PreMSI did not have higher predictive power than preSI. Additionally, in predicting hospital mortality, preMSI was not superior to preSI.

Changes in Relative Importance of the 5-Level Triage System, Korean Triage and Acuity Scale, for the Disposition of Emergency Patients Induced by Forced Reduction in Its Level Number: a Multi-Center Registry-based Retrospective Cohort Study.

BACKGROUND: The 5-level triage tool, the Korean Triage and Acuity Scale (KTAS), was developed based on the Canadian Triage and Acuity Scale and has been used for triage in all emergency medical institutions in Korea since 2016. This study evaluated the association between the decrease in level number and the change in its relative importance for disposition in the emergency department (ED). METHODS: Using the registry of the National Emergency Department Information System (NEDIS) ver. 3.1, data regarding consecutive emergency patients from March 2017 to October 2017 were reviewed retrospectively. Reconfiguring KTAS levels, a total of 15 multinomial logistic regression models (KTAS_0 to KTAS_14), including the KTAS, its variants, and covariates were constructed to determine significant factors affecting ED disposition. The relative importance of each model was obtained using a dominance analysis. RESULTS: A total of 79,771 patients were included in the analysis. In the model KTAS_0, the KTAS and 8 covariates were found to be significantly related to ED disposition. The KTAS and the decision maker of each ED visit, whether it was the physician or others, had the largest relative importance, 34.8% and 31.4%, respectively (P < 0.001). In other models of KTAS variants, including 4-level, 3-level and 2-level, the rates of the KTAS decreased to 31.8% (interquartile range [IQR], 28.9-34.2), 26.4% (IQR, 23.2-31.0), and 18.7% (IQR, 7.5-24.9), respectively (P = 0.016). On the other hand, the rates for covariates tended to be larger for smaller triage levels and so there was a significant interaction effect between the KTAS and the covariates according to the triage level (P < 0.001). CONCLUSION: The 5-level triage tool, the KTAS, had the largest relative importance among the predictors affecting ED disposition only at its original level. Therefore, it is recommended that no attempt should be made to reduce the number of levels in the triage tool.

Multiple cerebral infarct with cerebral vasculitis in a young patient with ulcerative colitis.

Ulcerative colitis (UC) is a chronic and debilitating disorder, characterized by inflammation of the colonic mucosa. UC can be considered a systemic disorder but UC-related manifestations in the central nervous system (CNS) are quite rare. A 29-year-old man was admitted to the emergency department with repeated generalized tonic-clonic (GTC) type seizures. Based on brain CT, brain metastasis or hemorrhagic infarct was suspected. Diffusion-weighted image of brain MRI showed high signal in the left thalamus and heterogenous enhancement in the right parietal and left frontal lobes. This image indicated a cerebral infarct, but could not completely rule out cerebral metastasis and vasculitis, or any other pathology. However, the brain biopsy revealed multiple thromboemboli with acute inflammation and necrosis. Thus, the patient was diagnosed with multiple cerebral infarcts with cerebral vasculitis, occurring as a complication of UC. In conclusion, CNS manifestations of UC are rare. However, clinicians should consider uncommon diagnoses like vasculitis and thromboembolism in patients with UC presenting with seizures.

The effect of hydraulic bed movement on the quality of chest compressions.

OBJECTIVES: The hydraulic height control systems of hospital beds provide convenience and shock absorption. However, movements in a hydraulic bed may reduce the effectiveness of chest compressions. This study investigated the effects of hydraulic bed movement on chest compressions. MATERIALS AND METHODS: Twenty-eight participants were recruited for this study. All participants performed chest compressions for 2min on a manikin and three surfaces: the floor (Day 1), a firm plywood bed (Day 2), and a hydraulic bed (Day 3). We considered 28 participants of Day 1 as control and each 28 participants of Day 2 and Day 3 as study subjects. The compression rates, depths, and good compression ratios (>5-cm compressions/all compressions) were compared between the three surfaces. RESULTS: When we compared the three surfaces, we did not detect a significant difference in the speed of chest compressions (p=0.582). However, significantly lower values were observed on the hydraulic bed in terms of compression depth (p=0.001) and the good compression ratio (p=0.003) compared to floor compressions. When we compared the plywood and hydraulic beds, we did not detect significant differences in compression depth (p=0.351) and the good compression ratio (p=0.391). CONCLUSIONS: These results indicate that the movements in our hydraulic bed were associated with a non-statistically significant trend towards lower-quality chest compressions.

Does cardiac catheterization laboratory activation by electrocardiography machine auto-interpretation reduce door-to-balloon time?

OBJECTIVES: In an attempt to begin ST-segment elevation myocardial infarction (STEMI) treatment more quickly (referred to as door-to-balloon [DTB] time) by minimizing preventable delays in electrocardiogram (ECG) interpretation, cardiac catheterization laboratory (CCL) activation was changed from activation by the emergency physician (code heart I) to activation by a single page if the ECG is interpreted as STEMI by the ECG machine (ECG machine auto-interpretation) (code heart II). We sought to determine the impact of ECG machine auto-interpretation on CCL activation. METHODS: The study period was from June 2010 to May 2012 (from June to November 2011, code heart I; from December 2011 to May 2012, code heart II). All patients aged 18 years or older who were diagnosed with STEMI were evaluated for enrollment. Patients who experienced the code heart system were also included. Door-to-balloon time before and after code heart system were compared with a retrospective chart review. In addition, to determine the appropriateness of the activation, we compared coronary angiography performance rate and percentage of STEMI between code heart I and II. RESULTS: After the code heart system, the mean DTB time was significantly decreased (before, 96.51 ± 65.60 minutes; after, 65.40 ± 26.40 minutes; P = .043). The STEMI diagnosis and the coronary angiography performance rates were significantly lower in the code heart II group than in the code heart I group without difference in DTB time. CONCLUSION: Cardiac catheterization laboratory activation by ECG machine auto-interpretation does not reduce DTB time and often unnecessarily activates the code heart system compared with emergency physician-initiated activation. This system therefore decreases the appropriateness of CCL activation.

Modification of termination of resuscitation rule with compression time interval in South Korea.

This study aimed to validate the predictive performance of the termination of resuscitation (TOR) rule and examine the compression time interval (CTI) as a criterion for modifying the rule. This retrospective observational study analyzed adult out-of-hospital cardiac arrest (OHCA) patients attended by emergency medical service (EMS) providers in mixed urban-rural areas in Korea in 2020 and 2021. We evaluated the predictive performance of basic life support (BLS) and the Korean Cardiac Arrest Research Consortium (KoCARC) TOR rule using the false-positive rate (FPR) and positive predictive value (PPV). We modified the age cutoff criterion and examined the CTI as a new criterion. According to the TOR rule, 1827 OHCA patients were classified into two groups. The predictive performance of the BLS TOR rule had an FPR of 11.7% (95% confidence interval (CI): 5.9-17.5) and PPV of 98.4% (97.6-99.2) for mortality, and an FPR of 3.6% (0.0-7.8) and PPV of 78.6% (75.9-81.3) for poor neurological outcomes at hospital discharge. The predictive performance of the KoCARC TOR rule had an FPR of 5.0% (1.1-8.9) and PPV of 98.9% (98.0-99.8) for mortality, and an FPR of 3.7% (0.0-7.8) and PPV of 50.0% (45.7-54.3) for poor neurological outcomes at hospital discharge. The modified cutoff value for age was 68 years, with an area under the receiver operating characteristic curve over 0.7. In the group that met the BLS TOR rule, the cutoff of the CTI for death was not determined and was 21 min for poor neurological outcomes. In the group that met the KoCARC TOR rule, the cutoff of the CTI for death and poor neurological outcomes at the time of hospital discharge was 25 min and 21 min, respectively. The BLS TOR and KoCARC TOR rules showed inappropriate predictive performance for mortality and poor neurological outcomes. However, the predictive performance of the TOR rule could be supplemented by modifying the age criterion and adding the CTI criterion of the KoCARC.

Acute phlegmonous esophagitis presenting as chest pain: A case report.

RATIONALE: Acute phlegmonous esophagitis (APE) is bacterial infection of the submucosal and muscularis layers of the esophagus. APE is a rare but life-threatening disease, and few studies have reported it. PATIENT CONCERNS: A 63-year-old Korean woman was admitted to the emergency department complaining of chest pain. Contrast-enhanced computed tomography revealed diffuse esophageal wall thickening with low attenuation and paraesophageal fluid collection in the mediastinum. Esophagomyotomy, mediastinal abscess drainage with a right thoracotomy, and left 3-port video-assisted thoracoscopy were performed in the operating room. DIAGNOSES: Contrast-enhanced computed tomography revealed diffuse esophageal wall thickening with low attenuation and paraesophageal fluid collection in the mediastinum. INTERVENTIONS: Esophagomyotomy, mediastinal abscess drainage with a right thoracotomy, and left 3-port video-assisted thoracoscopy were performed in the operating room. OUTCOMES: The patient followed up through an outpatient visit 4 days later discharged. The patient progress was good, and she decided to visit the patient if she had pain afterwards. LESSONS: As APE is rare but deadly, strategies to identify APE in patients with chest pain or dysphagia are needed in emergency department.

Predicting in-hospital cardiac arrest outcomes: CASPRI and GO-FAR scores.

It is important to predict the neurological prognoses of in-hospital cardiac arrest (IHCA) patients immediately after recovery of spontaneous circulation (ROSC) to make further critical management. The aim of this study was to confirm the usefulness of the Cardiac Arrest Survival Post-Resuscitation In-hospital (CASPRI) and Good Outcome Following Attempted Resuscitation (GO-FAR) scores for predicting the IHCA immediately after the ROSC. This is a retrospective analysis of patient data from a tertiary general hospital located in South Korea. A total of 488 adult patients who had IHCA and achieved sustained ROSC from September 2016 to August 2021 were analyzed to compare effectiveness of the CASPRI and GO-FAR scores related to neurologic prognosis. The primary outcome was Cerebral Performance Category (CPC) score at discharge, defined as a CPC score of 1 or 2. The secondary outcomes were survival-to-discharge and normal neurological status or minimal neurological damage at discharge. Of the 488 included patients, 85 (20.8%) were discharged with good prognoses (CPC score of 1 or 2). The area under the receiver operating characteristic curve of CASPRI score for the prediction of a good neurological outcome was 0.75 (95% CI 0.69-0.81), whereas that of GO-FAR score was 0.67 (95% CI 0.60-0.73). The results of this study show that these scoring systems can be used for timely and satisfactory prediction of the neurological prognoses of IHCA patients after ROSC.

Acceptability of the 8-case objective structured clinical examination of medical students in Korea using generalizability theory: a reliability study

PURPOSE: This study investigated whether the reliability was acceptable when the number of cases in the objective structured clinical examination (OSCE) decreased from 12 to 8 using generalizability theory (GT). METHODS: This psychometric study analyzed the OSCE data of 439 fourth-year medical students conducted in the Busan and Gyeongnam areas of South Korea from July 12 to 15, 2021. The generalizability study (G-study) considered 3 facets­students (p), cases (c), and items (i)­and designed the analysis as p×(i:c) due to items being nested in a case. The acceptable generalizability (G) coefficient was set to 0.70. The G-study and decision study (D-study) were performed using G String IV ver. 6.3.8 (Papawork, Hamilton, ON, Canada). RESULTS: All G coefficients except for July 14 (0.69) were above 0.70. The major sources of variance components (VCs) were items nested in cases (i:c), from 51.34% to 57.70%, and residual error (pi:c), from 39.55% to 43.26%. The proportion of VCs in cases was negligible, ranging from 0% to 2.03%. CONCLUSION: The case numbers decreased in the 2021 Busan and Gyeongnam OSCE. However, the reliability was acceptable. In the D-study, reliability was maintained at 0.70 or higher if there were more than 21 items/case in 8 cases and more than 18 items/case in 9 cases. However, according to the G-study, increasing the number of items nested in cases rather than the number of cases could further improve reliability. The consortium needs to maintain a case bank with various items to implement a reliable blueprinting combination for the OSCE.

Disparities in Survival Outcomes of Out-of-Hospital Cardiac Arrest Patients between Urban and Rural Areas and the Identification of Modifiable Factors in an Area of South Korea.

This retrospective study aimed to compare the survival outcomes of adult out-of-hospital cardiac arrest (OHCA) patients between urban (Busan, Ulsan, Changwon) and rural (Gyeongnam) areas in South Korea and identify modifiable factors in the chain of survival. The primary and secondary outcomes were survival to discharge and modifiable factors in the chain of survival were identified using logistic regression analysis. In total, 1954 patients were analyzed. The survival to discharge rates in the whole region and in urban and rural areas were 6.9%, 8.7% (Busan 8.7%, Ulsan 10.3%, Changwon 7.2%), and 3.4%, respectively. In the urban group, modifiable factors associated with survival to discharge were no advanced airway management (adjusted odds ratio (aOR) 2.065, 95% confidence interval (CI): 1.138-3.747), no mechanical chest compression (aOR 3.932, 95% CI: 2.015-7.674), and an emergency medical service (EMS) transport time of more than 8 min (aOR 3.521, 95% CI: 2.075-5.975). In the rural group, modifiable factors included an EMS scene time of more than 15 min (aOR 0.076, 95% CI: 0.006-0.883) and an EMS transport time of more than 8 min (aOR 4.741, 95% CI: 1.035-21.706). To improve survival outcomes, dedicated resources and attention to EMS practices and transport time in urban areas and EMS scene and transport times in rural areas are needed.

Comparing the cut score for the borderline group method and borderline regression method with norm-referenced standard setting in an objective structured clinical examination in medical school in Korea.

PURPOSE: Setting standards is critical in health professions. However, appropriate standard setting methods do not always apply to the set cut score in performance assessment. The aim of this study was to compare the cut score when the standard setting is changed from the norm-referenced method to the borderline group method (BGM) and borderline regression method (BRM) in an objective structured clinical examination (OSCE) in medical school. METHODS: This was an explorative study to model of the BGM and BRM. A total of 107 fourth-year medical students attended the OSCE at seven stations with encountering standardized patients (SPs) and one station with performing skills on a manikin on 15 July 2021. Thirty-two physician examiners evaluated the performance by completing a checklist and global rating scales. RESULTS: The cut score of the norm-referenced method was lower than that of the BGM (p<0.01) and BRM (p<0.02). There was no significant difference in the cut score between the BGM and BRM (p=0.40). The station with the highest standard deviation and the highest proportion of the borderline group showed the largest cut score difference in standard setting methods. CONCLUSION: Prefixed cut scores by the norm-referenced method without considering station contents or examinee performance can vary due to station difficulty and content, affecting the appropriateness of standard setting decisions. If there is an adequate consensus on the criteria for the borderline group, standard setting with the BRM could be applied as a practical and defensible method to determine the cut score for OSCE.

Effect of Prehospital Epinephrine Use on Survival from Out-of-Hospital Cardiac Arrest and on Emergency Medical Services.

This study was to identify the effect of epinephrine on the survival of out-of-hospital cardiac arrest (OHCA) patients and changes in prehospital emergency medical services (EMSs) after the introduction of prehospital epinephrine use by EMS providers. This was a retrospective observational study comparing two groups (epinephrine group and norepinephrine group). We used propensity score matching of the two groups and identified the association between outcome variables regarding survival and epinephrine use, controlling for confounding factors. The epinephrine group was 339 patients of a total 1943 study population. The survival-to-discharge rate and OR (95% CI) of the epinephrine group were 5.0% (p = 0.215) and 0.72 (0.43-1.21) in the total patient population and 4.7% (p = 0.699) and 1.15 (0.55-2.43) in the 1:1 propensity-matched population. The epinephrine group received more mechanical chest compression and had longer EMS response times and scene times than the norepinephrine group. Mechanical chest compression was a negative prognostic factor for survival to discharge and favorable neurological outcomes in the epinephrine group. The introduction of prehospital epinephrine use in OHCA patients yielded no evidence of improvement in survival to discharge and favorable neurological outcomes and adversely affected the practice of EMS providers, exacerbating the factors negatively associated with survival from OHCA.

Targeted suicide gene therapy for liver cancer based on ribozyme-mediated RNA replacement through post-transcriptional regulation.

Hepatocellular carcinoma (HCC) has high fatality rate and limited therapeutic options. Here, we propose a new anti-HCC approach with high cancer-selectivity and efficient anticancer effects, based on adenovirus-mediated Tetrahymena group I trans-splicing ribozymes specifically inducing targeted suicide gene activity through HCC-specific replacement of telomerase reverse transcriptase (TERT) RNA. To confer potent anti-HCC effects and minimize hepatotoxicity, we constructed post-transcriptionally enhanced ribozyme constructs coupled with splicing donor and acceptor site and woodchuck hepatitis virus post-transcriptional regulatory element under the control of microRNA-122a (miR-122a). Adenovirus encoding post-transcriptionally enhanced ribozyme improved trans-splicing reaction and decreased human TERT (hTERT) RNA level, efficiently and selectively retarding hTERT-positive liver cancers. Adenovirus encoding miR-122a-regulated ribozyme caused selective liver cancer cytotoxicity, the efficiency of which depended on ribozyme expression level relative to miR-122a level. Systemic administration of adenovirus encoding the post-transcriptionally enhanced and miR-regulated ribozyme caused efficient anti-cancer effects at a single dose of low titers and least hepatotoxicity in intrahepatic multifocal HCC mouse xenografts. Minimal liver toxicity, tissue distribution, and clearance pattern of the recombinant adenovirus were observed in normal animals administered either systemically or via the hepatic artery. Post-transcriptionally regulated RNA replacement strategy mediated by a cancer-specific ribozyme provides a clinically relevant, safe, and efficient strategy for HCC treatment.

Improved Intrinsic Nonlinear Characteristics of Ta2O5/Al2O3-Based Resistive Random-Access Memory for High-Density Memory Applications.

The major hindrance for high-density application of two-terminal resistive random-access memory (RRAM) array design is unintentional sneak path leakage through adjacent cells. Herein, we propose a bilayer structure of Ta2O5/Al2O3-based bipolar type RRAM by evaluating the intrinsic nonlinear characteristics without integration with an additional transistor and selector device. We conducted X-ray photoelectron spectroscopy (XPS) analysis with different etching times to verify Ta2O5/Al2O3 layers deposited on the TiN bottom electrode. The optimized nonlinear properties with current suppression are obtained by varying Al2O3 thickness. The maximum nonlinearity (~71) is achieved in a Ta2O5/Al2O3 (3 nm) sample. Furthermore, we estimated the comparative read margin based on the I-V characteristics with different thicknesses of Al2O3 film for the crossbar array applications. We expect that this study about the effect of the Al2O3 tunnel barrier thickness on Ta2O5-based memristors could provide a guideline for developing a selector-less RRAM application.

Synaptic Characteristics of Amorphous Boron Nitride-Based Memristors on a Highly Doped Silicon Substrate for Neuromorphic Engineering.

In this study, the resistive switching and synaptic properties of a complementary metal-oxide semiconductor-compatible Ti/a-BN/Si device are investigated for neuromorphic systems. A gradual change in resistance is observed in a positive SET operation in which Ti diffusion is involved in the conducting path. This operation is extremely suitable for synaptic devices in hardware-based neuromorphic systems. The isosurface charge density plots and experimental results confirm that boron vacancies can help generate a conducting path, whereas the conducting path generated by a Ti cation from interdiffusion forms is limited. A negative SET operation causes a considerable decrease in the formation energy of only boron vacancies, thereby increasing the conductivity in the low-resistance state, which may be related to RESET failure and poor endurance. The pulse transient characteristics, potentiation and depression characteristics, and good retention property of eight multilevel cells also indicate that the positive SET operation is more suitable for a synaptic device owing to the gradual modulation of conductance. Moreover, pattern recognition accuracy is examined by considering the conductance values of the measured data in the Ti/a-BN/Si device as the synaptic part of a neural network. The linear and symmetric synaptic weight update in a positive SET operation with an incremental voltage pulse scheme ensures higher pattern recognition accuracy.