Elucidating the Functional Roles of Helper and Cytotoxic T Cells in the Cell-Mediated Immune Responses of Olive Flounder (Paralichthys olivaceus).

In higher vertebrates, helper and cytotoxic T cells, referred to as CD4 and CD8 T lymphocytes, respectively, are mainly associated with adaptive immunity. The adaptive immune system in teleosts involves T cells equivalent to those found in mammals. We previously generated monoclonal antibodies (mAbs) against olive flounder (Paralichthys olivaceus) CD4 T cells, CD4-1 and CD4-2, and used these to describe the olive flounder's CD4 Tcell response during a viral infection. In the present study, we successfully produced mAbs against CD8 T lymphocytes and their specificities were confirmed using immuno-blotting, immunofluorescence staining, flow cytometry analysis andreverse transcription polymerase chain reaction (RT-PCR). The results showed that these mAbs are specific for CD8 T lymphocytes. We also investigated variations in CD4 and CD8 T cells populations, and analyzed the expression of immune-related genes expressed by these cells in fish infected with nervous necrosis virus or immunized with thymus dependent and independent antigens. We found that both CD4 and CD8 T lymphocyte populations significantly increased in these fish and Th1-related genes were up-regulated compared to the control group. Collectively, these findings suggest that the CD4 and CD8 T lymphocytes in olive flounder are similar to the helper and cytotoxic T cells found in mammals, and Th1 and cytotoxic immune responses are primarily involved in the early adaptive immune response against extracellular antigens.

Complex interaction of fasting glucose, body mass index, age and sex on all-cause mortality: a cohort study in 15 million Korean adults.

AIMS/HYPOTHESIS: The aim of this work was to examine whether synergistic associations with mortality exist for BMI and fasting blood glucose (FBG) and to identify FBG-BMI combined subgroups with higher mortality according to sex and age. METHODS: A total of 15,149,275 Korean adults participated in health examinations during 2003-2006 and were followed up until December 2018. Mortality HRs of 40 FBG-BMI combined groups were assessed by Cox proportional hazards models. RESULTS: During a mean 13.7 years of follow-up, 1,213,401 individuals died. A J-shaped association was seen between FBG and all-cause mortality for all BMI categories. Those with BMI <20 kg/m2 had the highest mortality for any given FBG level, followed by those with BMI 20-22.4 kg/m2. The detrimental effect of elevated FBG was greater among leaner individuals than more corpulent individuals. Moreover, the synergistic adverse effects of hyperglycaemia and leanness was stronger in younger adults than in older adults. Compared with the reference group (overweight with normoglycaemia), age- and sex-adjusted HRs of the leanest with normoglycaemia (BMI <20 kg/m2 and FBG 4.4-5.2 mmol/l), overweight with diabetes (BMI 25-27.4 kg/m2 and FBG ≥10.0 mmol/l) and leanest with diabetes (BMI <20 kg/m2 and FBG ≥10.0 mmol/l) were 1.29, 2.59 and 11.18, respectively, in those aged 18-44 years and 1.56, 1.72 and 2.87, respectively, in those aged 75-99 years. The identification of BMI-FBG subgroups associated with higher mortality was not straightforward, illustrated by the group with FBG 6.1-6.9 mmol/l and BMI 20-22.4 kg/m2 having a similar or higher mortality compared with the group with FBG 7.0-9.9 mmol/l and BMI ≥22.5 kg/m2. In women aged <45 years with FBG <6.9 mmol/l, those with BMI ≥27.5 kg/m2 had the highest mortality, whereas individuals with BMI <20 kg/m2 had the highest mortality for each given FBG level in other age and sex groups. CONCLUSIONS/INTERPRETATION: Leanness and hyperglycaemia interact together to increase mortality in a supra-multiplicative manner, especially in younger adults; the interactions of BMI, FBG, sex and age with mortality are complex. Graphical abstract.

Comparison of urologic complications between laparoscopic radical hysterectomy and abdominal radical hysterectomy: A nationwide study from the National Health Insurance.

OBJECTIVE: This study aimed to assess the risks of intraoperative and postoperative urologic complications between laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH). METHODS: Using the database of the National Health Insurance Service (NHIS) and Health Insurance Review & Assessment (HIRA), we identified all Korean women who underwent radical hysterectomy between 2006 and 2018. Intraoperative and postoperative urologic complications were compared between the ARH and LRH groups. RESULTS: A total of 11,399 patients were identified to ARH and 8435 patients to LRH. Urologic complications occurred in 292 of 19,774 patients (1.48%) who underwent radical hysterectomy. LRH was associated with higher complication rates than ARH, although with a borderline significance (OR: 1.23; 90% CI: 1.02-1.51, p = 0.066). There was no difference in intraoperative urologic complications between the ARH and the LRH groups (OR: 1.1 95% CI: 0.86-1.43, p < 0.435). The incidence of postoperative urologic complications was significantly higher in the LRH group (OR: 2.01; 95% CI: 1.18-3.47, p = 0.009). In terms of postoperative urologic complications, the risk of ureterovaginal fistula was not significant between the two groups (OR: 1.53; 95% CI: 0.54-4.24, p = 0.403), whereas the risk of vesicovaginal fistula was significantly higher in the LRH group (OR: 2.24; 95% CI: 1.09-4.58, p = 0.028). There were no significant differences in the overall and urinary tract-specific complications between ARH and LRH in groups under 40 years of age and during the second half (2013-2018), with 2012 as the boundary. CONCLUSION: Among specific urologic complications, the incidence of vesicovaginal fistula was significantly higher in the LRH group than in the ARH group.

The relationship between metabolic syndrome and the incidence of colorectal cancer.

OBJECTIVES: This study evaluated the incidence of colorectal cancer (CRC) according to the number of metabolic syndrome (MetS) components. METHODS: Using health checkup and insurance claims data of 6,365,409 subjects, the occurrence of CRC according to stage of MetS by sex was determined from the date of the health checkup in 2009 until December 31, 2018. RESULTS: Cumulative incidence rates (CIR) of CRC in men and women was 3.9 and 2.8 per 1000 (p < 0.001), respectively. CIR of CRC for the normal, pre-MetS, and MetS groups in men was 2.6, 3.9, and 5.5 per 1000 (p < 0.001) and CIR in women was 2.1, 2.9, and 4.5 per 1000 (p < 0.001), respectively. Compared with the normal group, the hazard ratio (HR) of CRC for the pre-MetS group was 1.25 (95% CI 1.17-1.33) in men and 1.09 (95% CI 1.02-1.17) in women, and the HR of CRC for the MetS group was 1.54 (95% CI 1.43-1.65) in men and 1.39 (95% CI 1.26-1.53) in women after adjustment. CONCLUSIONS: We found that MetS is a risk factor for CRC in this study. Therefore, the prevention and active management of MetS would contribute to the prevention of CRC.

Long-term impact of dialysis-requiring AKI during the perioperative period of liver transplantation on postdischarge outcomes.

BACKGROUND: Patients undergoing liver transplantation (LT) are prone to dialysis-requiring acute kidney injury (AKI-D). However, long-term prognoses among them need further investigation, as overall survival after LT is improving. METHODS: A nationwide, population-based cohort study was conducted using the data of Korean National Health Insurance System between 2006 and 2015. The patients who received dialysis during the perioperative period of LT were in the AKI-D group, and the control group included those who did not undergo dialysis. RESULTS: Among the 6879 patients who underwent LT, 968 were in the AKI-D group. All-cause mortality [adjusted hazard ratio (HR): 1.52 (1.26-1.83), P < 0.001], end-stage renal disease (ESRD) progression [adjusted HR: 2.93 (2.34-3.66), P < 0.001], and ICU readmission [adjusted HR: 1.70 (1.44-2.01), P < 0.001] within and after 90 days from discharge were increased in the AKI-D group. When analyzed among those who recovered from dialysis at discharge, overall outcomes were similar to those of the AKI-D group, except the long-term mortality. CONCLUSIONS: AKI-D during the perioperative period of LT was associated with worse mortality, ESRD progression, and ICU readmission risk. The results of renal-recovered patients could indicate clinicians that achievement of dialysis independence is important to gain favorable long-term postdischarge survival.

Emerging memory technologies for neuromorphic computing.

In this paper, we reviewed the recent trends on neuromorphic computing using emerging memory technologies. Two representative learning algorithms used to implement a hardware-based neural network are described as a bio-inspired learning algorithm and software-based learning algorithm, in particular back-propagation. The requirements of the synaptic device to apply each algorithm were analyzed. Then, we reviewed the research trends of synaptic devices to implement an artificial neural network.

Gated Schottky Diode-Type Synaptic Device with a Field-Plate Structure to Reduce the Forward Current.

A gated Schottky diode with a field-plate structure is proposed and investigated as a new low-power synaptic device to suppress the forward current of the Schottky diode. In a hardware-based neural network, unwanted forward current can flow through gated Schottky diode-type synaptic devices during integration operations, possibly causing a malfunction of the neural network and increasing the power consumption. By adopting a field-plate structure, a virtual pn junction to suppress the forward current of the Schottky diode is formed in the poly-Si active layer. As a result, the unwanted forward current of the gated Schottky diode is successfully reduced to less than 1 pA/µm.

Postdischarge Major Adverse Cardiovascular Events of ICU Survivors Who Received Acute Renal Replacement Therapy.

OBJECTIVES: Long-term risk of a major adverse cardiovascular events in ICU survivors who underwent acute renal replacement therapy requires further investigation. DESIGN: Nationwide population-based study using the claims database of Korea. SETTING: Index admission cases of ICU survivors in government-designated tertiary hospitals PATIENTS:: The study group consisted of ICU survivors who underwent acute renal replacement therapy, and the control group consisted of those without acute renal replacement therapy. Patients were excluded if they 1) were under age 20, 2) expired within 30 days after discharge, 3) received ICU care for less than 24 hours, 4) had a previous ICU admission, 5) had a history of major adverse cardiovascular event, or 6) had a major adverse cardiovascular event-related cardio/cerebrovascular diseases. The outcomes of the patients who received continuous renal replacement therapy were compared with those of patients who received only intermittent renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Information regarding patient characteristics and treatment modalities was collected and adjusted. The main outcome was major adverse cardiovascular event, including acute myocardial infarction, revascularization, and acute ischemic stroke. Patient mortality and progression to end-stage renal disease were also evaluated. We included 12,380 acute renal replacement therapy patients and 382,018 patients in the control group. Among the study group, 6,891 patients were included in the continuous renal replacement therapy group, and 5,034 in the intermittent renal replacement therapy group. The risks of major adverse cardiovascular event (adjusted hazard ratio, 1.463 [1.323-1.619]; p < 0.001), all-cause mortality (adjusted hazard ratio, 1.323 [1.256-1.393]; p < 0.001), and end-stage renal disease (adjusted hazard ratio, 18.110 [15.779-20.786]; p < 0.001) were higher in the acute renal replacement therapy patients than the control group. When we compared the continuous renal replacement therapy patients with the intermittent renal replacement therapy patients, the risk of major adverse cardiovascular event was comparable (adjusted hazard ratio, 1.049 [0.888-1.239]; p = 0.575). CONCLUSIONS: Clinicians should note the increased risk of a long-term major adverse cardiovascular event in acute renal replacement therapy patients and consider appropriate risk factor management. Significant difference in the risk of postdischarge major adverse cardiovascular event was not identified between continuous renal replacement therapy and intermittent renal replacement therapy.

DM-MQTT: An Efficient MQTT Based on SDN Multicast for Massive IoT Communications.

Edge computing is proposed to solve the problem of centralized cloud computing caused by a large number of IoT (Internet of Things) devices. The IoT protocols need to be modified according to the edge computing paradigm, where the edge computing devices for analyzing IoT data are distributed to the edge networks. The MQTT (Message Queuing Telemetry Transport) protocol, as a data distribution protocol widely adopted in many international IoT standards, is suitable for cloud computing because it uses a centralized broker to effectively collect and transmit data. However, the standard MQTT may suffer from serious traffic congestion problem on the broker, causing long transfer delays if there are massive IoT devices connected to the broker. In addition, the big data exchange between the IoT devices and the broker decreases network capability of the edge networks. The authors in this paper propose a novel MQTT with a multicast mechanism to minimize data transfer delay and network usage for the massive IoT communications. The proposed MQTT reduces data transfer delays by establishing bidirectional SDN (Software Defined Networking) multicast trees between the publishers and the subscribers by means of bypassing the centralized broker. As a result, it can reduce transmission delay by 65% and network usage by 58% compared with the standard MQTT.

Medical visits, antihypertensive prescriptions and medication adherence among newly diagnosed hypertensive patients in Korea.

OBJECTIVES: The objective of this study was to assess the antihypertensive medication adherence in patients who were newly diagnosed with hypertension in Korea. METHODS: Study subjects were diagnosed with hypertension for the first time by the General Health Screening in 2012 and were 65,919. As indices, visiting rate to medical institution, the antihypertensive prescription rate, medication possession ratio and the rate of appropriate medication adherence were used. The qualification data, the General Health Screening data and the health insurance claims data were used. RESUTLS: Visiting rate to medical institution within one-year was 42.3%. Gender, age, family history of hypertension, smoking status, drinking frequency, insurance type, BMI, hypertension status, blood glucose level and LDL-cholesterol level were significant variables for visiting a medical institution. Of the study subjects who visited a medical institution, the antihypertensive prescription rate was 89.1%. Medication possession ratio was 70.9% and the rate of appropriate medication adherence was 60.6%. Age, family history of hypertension, smoking status, BMI level, hypertension level, blood glucose level, status, and LDL-cholesterol level were significant variables for the antihypertensive prescription and gender, age, family history of hypertension, smoking status, BMI, hypertension status, and the time of the first visit to a medical institution were significant variables for appropriate medication adherence. CONCLUSIONS: This study showed that the antihypertensive medication adherence in patients who were newly diagnosed with hypertension was not relatively high in Korea. National Health Insurance Service should support an environment in which medical institutions and those diagnosed with hypertension can fulfill their roles.

Retrospective observation on contribution and limitations of screening for breast cancer with mammography in Korea: detection rate of breast cancer and incidence rate of interval cancer of the breast.

BACKGROUND: The purpose of this study was to determine the benefits and limitations of screening for breast cancer using mammography. METHODS: Descriptive design with follow-up was used in the study. Data from breast cancer screening and health insurance claim data were used. The study population consisted of all participants in breast cancer screening from 2009 to 2014. Crude detection rate, positive predictive value and sensitivity and specificity of breast cancer screening and, incidence rate of interval cancer of the breast were calculated. RESULTS: The crude detection rate of breast cancer screening per 100,000 participants increased from 126.3 in 2009 to 182.1 in 2014. The positive predictive value of breast cancer screening per 100,000 positives increased from 741.2 in 2009 to 1,367.9 in 2014. The incidence rate of interval cancer of the breast per 100,000 negatives increased from 51.7 in 2009 to 76.3 in 2014. The sensitivities of screening for breast cancer were 74.6% in 2009 and 75.1% in 2014 and the specificities were 83.1% in 2009 and 85.7% in 2014. CONCLUSIONS: To increase the detection rate of breast cancer by breast cancer screening using mammography, the participation rate should be higher and an environment where accurate mammography and reading can be performed and reinforcement of quality control are required. To reduce the incidence rate of interval cancer of the breast, it will be necessary to educate women after their 20s to perform self-examination of the breast once a month regardless of participation in screening for breast cancer.

Effect of diabetic case management intervention on health service utilization in Korea.

This study is to estimate the effectiveness of a diabetic case management programme on health-care service utilization. The study population included 6007 as the intervention group and 956,766 as the control group. As the indicators of health-care service utilization, numbers of medical ambulatory consultations, days of medication prescribed and medical expenses for one year were used, and we analysed the claim data of the health insurance from 2005 to 2007. The study population was classified into three subgroups based on the number of medical ambulatory consultations per year before this intervention. In the under-serviced subgroup, the intervention group showed a significant increase in the number of consultations (3.2), days of prescribed medication (66.4) and medical expenses (287,900 KRW) compared with the control group. Conversely, in the over-serviced subgroup, the intervention group showed a less decrease days of prescribed medication (1.6) compared with the control group. This showed that the case management programme led the intervention group to optimize their utilization of health-care services by subgroups. It is necessary to evaluate the appropriateness of health-care usage and clinical outcome to show the direct effectiveness of the case management programme by subgroups.

Implementation rate and related factors of confirmatory tests following an abnormal Pap smear: a nationwide study from the National Health Insurance.

OBJECTIVE: This study aims to investigate the implementation rate and influencing factors of confirmatory tests for women with abnormal cervical cytology results in the Korean nationwide cervical cancer screening program. METHODS: The National Health Insurance Service (NHIS) database was utilized to identify all Korean women who have participated in the Korean nationwide cervical cancer screening program from January 2011 and December 2021 using the NHIS database. Multiple logistic regression analysis was performed to estimate the multivariate odds ratio and evaluate the patients' characteristics. RESULTS: The rate of abnormal Papanicolaou (Pap) smears showed an initial increase from 2011 to 2015 and subsequently reached a plateau after 2016. When examining specific subcategories, cases of atypical squamous cells of undetermined significance (ASC-US) increased from 28,546 cases (1.1%) in 2011 to 62,850 cases (1.7%) in 2021. In contrast, cases of HSIL and SCC declined from 3,535 cases (0.14%) to 2,763 cases (0.07%) and from 383 cases (0.01%) to 179 cases (0.005%), respectively. Furthermore, the implementation rate of confirmatory tests for women with abnormal cytology increased from 8,865 cases (21.0%) in 2011 to 39,045 cases (51.2%) in 2021. Regarding the specific subcategory of ASC-US, the number of confirmatory tests exhibited a substantial increase from 4,101 cases (14.4%) in 2011 to 30,482 cases (48.5%) in 2021. For SCC, there was no significant change, with 216 cases (56.4%) in 2011 and 102 cases (57.0%) in 2021. The implementation rate of confirmatory tests was found to be significantly associated with results of abnormal Pap smear, age, and residence. Notably, economic status did not emerge as a significant factor affecting the likelihood of undergoing confirmatory tests. CONCLUSIONS: The severity of abnormal Pap smear results is a reliable indicator of the probability of undergoing a confirmatory test. Additional endeavors are required to improve the implementation rate among women who have received abnormal Pap smear results.

Anxiety, depression, and uncertainty appraisal and factors affecting uncertainty risk and opportunity appraisal of health care workers in Korea during the COVID-19 outbreak: Uncertainty risk and opportunity appraisal.

Background: Due to the prolonged period of COVID-19, the uncertainty related to COVID-19 is bound to increase for healthcare workers (HCWs) in tertiary medical institutions as much as for the HCWs in dedicated hospitals. Purpose: To assess anxiety, depression, and uncertainty appraisal, and to determine the factors affecting uncertainty risk and opportunity appraisal experienced by HCWs at the forefront of COVID-19 treatment. Method: This was a descriptive, cross-sectional study. The participants were HCWs at a tertiary medical center in Seoul. HCWs included medical (doctors, nurses) and non-medical (nutritionists, pathologists, radiologists, office workers, etc.) personnel. Self-reported structured questionnaires (patient health questionnaire, generalized anxiety disorder scale, and uncertainty appraisal) were obtained. Finally, responses from 1337 people were used to evaluate factors affecting uncertainty risk and opportunity appraisal using a quantile regression analysis. Results: The average ages of medical and non-medical HCWs were 31.69 ± 7.87 and 38.66 ± 11.42 years, and the proportion of females was high. The rates of moderate to severe depression (23.23%) and anxiety (6.83%) were higher in medical HCWs. The uncertainty risk score was higher than the uncertainty opportunity score for all the HCWs. Factors that increased uncertainty opportunity were a decrease in depression in medical HCWs and a decrease in anxiety in non-medical HCWs. Increase in age was directly proportional to uncertainty opportunity in both groups. Conclusion: There is a need to devise a strategy to reduce uncertainty among HCWs who inevitably face various infectious diseases that appear in the near future. In particular, since there are various types of non-medical as well as medical HCWs in medical institutions who can prepare an intervention plan that comprehensively considers the characteristics of each occupation and the distribution of risks and opportunities of uncertainty will be able to improve the quality of life of HCWs and further promote the health of the people.

Determinants of Working Practice Location for Clinicians According to High School, Medical School, and Resident Training Locations in Korea.

Although several regulations have been implemented for medical school admission, such as a quota system, the uneven distribution of healthcare personnel across regions is an unresolved problem in Korea. This study explores the distribution and retention rate of clinicians across regions according to the degree of experience staying in the current clinical area during high school/medical school/resident training using 2016 Korean Physician Survey data. Both in metropolitan and non-metropolitan areas, clinicians who completed high school, medical school, and resident training in the current practice region (Subgroup D) accounted for the largest proportion (Metro, n = 1611, 46.1%; non-metro, n = 1917, 52.9%). The retention rate was the highest in Subgroup D both in metropolitan (84.3%) and non-metropolitan areas (Chungcheong 86.2%, Jeolla 79.9%, Daegu/Gyeongbuk 81.6%, Busan/Ulsan/Gyeongnam 93.3%) except Gangwon and Jeju. The second, third, and fourth highest retention rates were observed in cases where clinicians completed their high school and resident training, medical school and resident training, and resident training only, respectively, in all regions, although the ranking differs by region. To increase the retention rate of physicians, this study shows that it is necessary for a student to seek ways to continue training in the same region in which they graduated from medical school.

Sex-Specific Relationships between HDL-Cholesterol Levels and 10-Year Mortality in Individuals with Atherosclerotic Cardiovascular Disease: A Nationwide Cohort Study of South Koreans.

Large epidemiological studies show U-shaped relationships between high-density lipoprotein cholesterol (HDL-C) levels and all-cause mortality in individuals without atherosclerotic cardiovascular diseases (ASCVD). Association in those with ASCVD by sex is unclear. We examined the association between HDL-C levels and 10-year all-cause mortality in subjects (≥40 years of age) with ASCVD using the 2010 National Health Insurance Service and the National Death Registry of Korea. We categorized HDL-C levels into three groups (low: <40 mg/dL for males, <50 mg/dL for females; high: 40-90 mg/dL for males, 50-90 mg/dL for females; extremely high: >90 mg/dL) and 10 mg/dL intervals. We conducted a sex-stratified and adjusted Cox proportional hazards analysis. Out of 1,711,548 individuals (54% female, mean age 61.4 years), 10-year mortality was observed in 218,252 (12.8%). Males had a higher mortality rate than females (16.2% vs. 9.8%; p < 0.001). When adjusting for age, body mass index, LDL-cholesterol, triglycerides, hypertension, diabetes, smoking, and alcohol consumption, the low and extremely high HDL-C groups had significantly higher hazard ratios for 10-year mortality compared to the high HDL-C group in males [1.183 (1.166-1.199), 1.359 (1.288-1.434)] and in females [1.153 (1.138-1.169), 1.095 (1.029-1.167)]. The frequency distribution bars for the 10-year mortality rate showed sex-specific nadirs of 50-59 mg/dL in males and 70-79 mg/dL in females. In this ASCVD cohort, the extremely high HDL-C (>90 mg/dL) group had 35.9% and 9.5% higher 10-year mortality risks than the high HDL-C group for males and females, respectively. There was a slightly U-shaped relationship between baseline HDL-C levels and a 10-year mortality rate, with earlier inflection in males than in females.

Association between Prehospital Visits and Poor Health Outcomes in Korean Acute Stroke Patients: A National Health Insurance Claims Data Study.

This study aimed to determine whether prehospital visits to other medical institutions before admission are associated with prolonged hospital stay, readmission, or mortality rates in acute stroke patients. Using the claims data from the Korean Health Insurance Service, a cross-sectional study was conducted on 58,418 newly diagnosed stroke patients aged ≥ 20 years from 1 January 2019 to 31 December 2019. Extended hospital stay (≥7 days; median value) following initial admission, readmission within 180 days after discharge, and all-cause mortality within 30 days were measured as health outcomes using multiple logistic regression analysis after adjusting for age, sex, income, residential area, and medical history. Stroke patients with a prehospital visit (10,992 patients, 18.8%) had a higher risk of long hospitalization (odds ratio = 1.06; 95% confidence interval = 1.02-1.10), readmission (1.19; 1.14-1.25), and mortality (1.23; 1.13-1.33) compared with patients without a prehospital visit. Female patients and those under 65 years of age had increased unfavorable outcomes (p < 0.05). Prehospital visits were associated with unfavorable health outcomes.

Efficient Hybrid Training Method for Neuromorphic Hardware Using Analog Nonvolatile Memory.

Neuromorphic hardware using nonvolatile analog synaptic devices provides promising advantages of reducing energy and time consumption for performing large-scale vector-matrix multiplication (VMM) operations. However, the reported training methods for neuromorphic hardware have appreciably shown reduced accuracy due to the nonideal nature of analog devices, and use conductance tuning protocols that require substantial cost for training. Here, we propose a novel hybrid training method that efficiently trains the neuromorphic hardware using nonvolatile analog memory cells, and experimentally demonstrate the high performance of the method using the fabricated hardware. Our training method does not rely on the conductance tuning protocol to reflect weight updates to analog synaptic devices, which significantly reduces online training costs. When the proposed method is applied, the accuracy of the hardware-based neural network approaches to that of the software-based neural network after only one-epoch training, even if the fabricated synaptic array is trained for only the first synaptic layer. Also, the proposed hybrid training method can be efficiently applied to low-power neuromorphic hardware, including various types of synaptic devices whose weight update characteristics are extremely nonlinear. This successful demonstration of the proposed method in the fabricated hardware shows that neuromorphic hardware using nonvolatile analog memory cells becomes a more promising platform for future artificial intelligence.

Reconfigurable neuromorphic computing block through integration of flash synapse arrays and super-steep neurons.

Neuromorphic computing (NC) architecture inspired by biological nervous systems has been actively studied to overcome the limitations of conventional von Neumann architectures. In this work, we propose a reconfigurable NC block using a flash-type synapse array, emerging positive feedback (PF) neuron devices, and CMOS peripheral circuits, and integrate them on the same substrate to experimentally demonstrate the operations of the proposed NC block. Conductance modulation in the flash memory enables the NC block to be easily calibrated for output signals. In addition, the proposed NC block uses a reduced number of devices for analog-to-digital conversions due to the super-steep switching characteristics of the PF neuron device, substantially reducing the area overhead of NC block. Our NC block shows high energy efficiency (37.9 TOPS/W) with high accuracy for CIFAR-10 image classification (91.80%), outperforming prior works. This work shows the high engineering potential of integrating synapses and neurons in terms of system efficiency and high performance.

Risk of cancer, cardiovascular disease, thromboembolism, and mortality in patients with rheumatoid arthritis receiving Janus kinase inhibitors: a real-world retrospective observational study using Korean health insurance data.

OBJECTIVES: This study investigated whether Janus kinase inhibitors (JAKis) raise the risk of cardiovascular disease (CVD), venous thromboembolism (VTE), and cancer in patients with rheumatoid arthritis (RA). METHODS: We conducted a real-world retrospective observational study using data obtained from the Korean National Health Insurance Service database. Two data sets were analyzed: tumor necrosis factor inhibitor (TNFi)/JAKi-naive RA patients (set 1) and all RA patients who used TNFis or JAKis (set 2). The incidence rate ratios (IRRs) and hazard ratios (HRs) for acute myocardial infarction (AMI), stroke, cardiovascular (CV)-related mortality, major adverse cardiovascular events (MACE), VTE, arterial thromboembolism (ATE), cancer, and all-cause mortality were compared between the JAKi and TNFi groups. RESULTS: Set 1 included 1,596 RA patients (JAKi group: 645; TNFi group: 951), and set 2 included 11,765 RA patients (JAKi group: 2,498; TNFi group: 9,267). No adverse events (AEs) showed significantly higher IRRs in the JAKi groups than in the TNFi groups of sets 1 and 2. The HRs for MACE in the JAKi groups of sets 1 and 2 were 0.59 (95% confidence [CI], 0.35 to 0.99) and 0.80 (95% CI, 0.67 to 0.97), respectively. The JAKi group of set 2 showed a significantly higher risk of all-cause mortality (HR, 1.71; 95% CI, 1.32 to 2.20), but the other AEs did not demonstrate increased risks in the JAKi groups. CONCLUSIONS: In this study, JAKis did not increase the risk of AMI, stroke, CV-related mortality, MACE, VTE, ATE, or cancer in Korean RA patients relative to TNFis.