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Background To validate the treatment target of low-density lipoprotein cholesterol (LDL-C) level according to the cardiovascular disease (CVD) risk which was recommended by Korean dyslipidemia guideline. Methods We used the Korean National Health Insurance Service database which included 3,958,048 people aged 20 to 89 years who underwent regular health screening. The primary outcome was incident CVD, defined as a composite of myocardial infarction and stroke during the follow-up period from 2009 to 2018. Results The risk of CVD increased from LDL-C level of 70 mg/dL in very high-risk and high-risk groups and from 130 mg/dL in moderate-risk and low-risk groups. Adjusted hazard ratios (HRs) of LDL-C ranges 70–99, 100–129, 130–159, 160–189, and ≥190 mg/dL were 1.20 (95% confidence interval [CI], 1.08–1.33), 1.27 (1.15–1.42), 1.39 (1.23–1.56), 1.69 (1.45–1.96), and 1.84 (1.49– 2.27) in very high-risk group, and 1.07 (1.02–1.13), 1.16 (1.10–1.21), 1.29 (1.22–1.36), 1.45 (1.36–1.55), and 1.73 (1.58–1.90) in high-risk group. Adjusted HRs (95% CI) of LDL-C ranges 130–159, 160–189, and ≥190 mg/dL were 1.15 (1.11–1.20), 1.28 (1.22– 1.34), and 1.45 (1.36–1.54) in moderate-risk group and 1.07 (1.02–1.13), 1.20 (1.13–1.26), and 1.47 (1.37–1.57) in low-risk group. Conclusion We confirmed the incidence of CVD was increased in higher LDL-C range. The risk of CVD increased from ≥70 mg/dL of LDL-C in very high-risk and high-risk groups, and from ≥130 mg/dL of LDL-C in moderate-risk and low-risk groups in Korean adults.

Abstract Emerging evidence reveals a close association between gut microbiota and human neurological disorders. The present study aimed to assess whether the composition of gut microbiota in participants with episodic migraine (EM) and chronic migraine (CM) was altered in comparison to that of the controls. This study was a cross-sectional, case–control study. The gut microbiota were evaluated by the partial, targeted sequencing of the 16S rRNA V3–V4 region. This study enrolled 42 and 45 participants with EM and CM, respectively, and 43 controls. Alpha and beta diversities revealed no significant difference among the three groups; however, the microbiota composition at the class, order, family, and genus levels differed significantly between EM and the control, CM and the control, and the EM and CM groups. Moreover, higher composition of PAC000195_g was significantly associated with a lower headache frequency among the five genera that exhibited significantly different microbiota composition in EM and CM. Agathobacter revealed a significant negative association with severe headache intensity. The findings of the present study provide evidence of altered gut microbiota in EM and CM. These findings will help in understanding the course and treatment of migraine.

Abstract The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. We obtained a total of 208 metabolites from the gutMgene database and retrieved 1256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD and therefore to understanding its processes and possible therapeutic approaches. The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights on which to base further research.

In this paper, we present a digital processing in memory (DPIM) configured as a stride edge-detection search frequency neural network (SE-SFNN) which is trained through spike location dependent plasticity (SLDP), a learning mechanism reminiscent of spike timing dependent plasticity (STDP). This mechanism allows for rapid online learning as well as a simple memory-based implementation. In particular, we employ a ternary data scheme to take advantage of ternary content addressable memory (TCAM). The scheme utilizes a ternary representation of the image pixels, and the TCAMs are used in a two-layer format to significantly reduce the computation time. The first layer applies several filtering kernels, followed by the second layer, which reorders the pattern dictionaries of TCAMs to place the most frequent patterns at the top of each supervised TCAM dictionary. Numerous TCAM blocks in both layers operate in a massively parallel fashion using digital ternary values. There are no complicated multiply operations performed, and learning is performed in a feedforward scheme. This allows rapid and robust learning as a trade-off with the parallel memory block size. Furthermore, we propose a method to reduce the TCAM memory size using a two-tiered minor to major promotion (M2MP) of frequently occurring patterns. This reduction scheme is performed concurrently during the learning operation without incurring a preconditioning overhead. We show that with minimal circuit overhead, the required memory size is reduced by 84.4%, and the total clock cycles required for learning also decrease by 97.31 % while the accuracy decreases only by 1.12%. We classified images with 94.58% accuracy on the MNIST dataset. Using a 100 MHz clock, our simulation results show that the MNIST training takes about 6.3 ms dissipating less than 4 mW of average power. In terms of inference speed, the trained hardware is capable of processing 5,882,352 images per second.

Abstract The aim of this study is to characterize the microRNA (miRNA) expression signatures in patients with thyroid eye disease (TED) and identify miRNA biomarkers of disease activity. Total RNA was isolated from the sera of patients with TED (n = 10) and healthy controls (HCs, n = 5) using the miRNeasy Serum/Plasma Kit. The NanoString assay was used for the comprehensive analysis of 798 miRNA expression profiles. Analysis of specific miRNA signatures, mRNA target pathway analysis, and network analysis were performed. Patients with TED were divided into two groups according to disease activity: active and inactive TED groups. Differentially expressed circulating miRNAs were identified and tested using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) tests in the validation cohort. Among the 798 miRNAs analyzed, 173 differentially downregulated miRNAs were identified in TED patients compared to those in the HCs. Ten circulating miRNAs were differentially expressed between the active and inactive TED groups and regarded as candidate biomarkers for TED activity (one upregulated miRNA: miR-29c-3p; nine downregulated miRNAs: miR-4286, miR-941, miR-571, miR-129-2-3p, miR-484, miR-192-5p, miR-502-3p, miR-597-5p, and miR-296-3p). In the validation cohort, miR-484 and miR-192-5p showed significantly lower expression in the active TED group than in the inactive TED group. In conclusion, the expression levels of miR-484 and miR-192-5p differed significantly between the active and inactive TED groups, suggesting that these miRNAs could serve as circulating biomarkers of TED activity, however, these findings need to be validated in further studies.

Although numerous studies have used systemic approaches to identify prognostic predictors in oral squamous cell carcinoma (OSCC), the effectiveness of these approaches has not been assessed clinically. Further, the mechanism underlying malignant behaviors in OSCC is poorly characterized. This study aimed to develop and verify accurate prognostic predictors for OSCC patients and assess the associated biology. We identified an OSCC‐recurrence‐related gene signature (ORGS) using a Cox regression analysis. Functional enrichment analysis was used to identify enriched pathways and biological processes to reveal the underlying mechanism of OSCC malignant behavior. The ORGS successfully divided OSCC patients into low‐ and high‐risk groups with significantly different overall survivals. Pathway analysis revealed oxidative phosphorylation (OXPHOS) as a signaling pathway associated with the ORGS in OSCC. Interestingly, high OXPHOS status was strongly associated with poor overall survival in OSCC patients. Mediator complex subunit 30 (MED30) was a predicted upstream regulator of OXPHOS, and knockdown of MED30 reduced histone acetylation. We identified that the ORGS was strongly correlated with OXPHOS regulatory processes, suggesting OXPHOS as a key mechanism leading to poor prognosis in OSCC.

Background/Aims The Korean Diabetes Association (KDA) guidelines recommend adults aged ≥ 40 years and adults aged ≥ 30 years with diabetes risk factors for diabetes screening. This study aimed to determine the age threshold for diabetes screening in Korean adults. Methods This study was based on the analyses of Korean adults aged ≥ 20 years using the Korea National Health and Nutrition Examination Survey (KNHANES) and the National Health Insurance Service-National Sample Cohort (NHIS-NSC). To evaluate screening effectiveness, we calculated the number needed to screen (NNS). Results NNS to detect diabetes decreased from 63 to 34 in the KNHANES and from 71 to 42 in the NHIS-NSC between the ages of 30–34 and 35–39. When universal screening was applied to adults aged ≥ 35, the NNS was similar to that of adults aged ≥ 40. Compared to the KDA guidelines, the rate of missed screening positive in adults aged ≥ 20 decreased from 4.0% to 0.2% when the newly suggested screening criteria were applied. Conclusions Universal screening for adults aged ≥ 35 and selective screening for adults aged 20 to 34, considering diabetes risk factors, may be appropriate for detecting prediabetes and diabetes in South Korea.

Background/Aims Women with rheumatoid arthritis (RA) are often diagnosed with the disease during their reproductive years; however, its incidence and prevalence among women of childbearing age have not been studied. The objective of this study was to estimate the incidence and prevalence of seropositive rheumatoid arthritis (SPRA) among Korean women of childbearing age. Methods Women aged 20 to 44 years with SPRA were identified from National Health Insurance Service-National Health Information Database (2009 to 2016). SPRA was defined by International Classification of Diseases, 10th revision code, M05. Incidence and prevalence were calculated per 100,000 person-years and stratified by year and age. Results The average incidence and prevalence of SPRA from 2011 to 2016 among women of childbearing age was 24.1/100,000 person-years (95% confidence interval [CI], 23.7 to 24.5) and 105.2/100,000 person-years (95% CI, 100.9 to 109.5), respectively. The incidence increased annually from 21.0/100,000 person-years (95% CI, 20.1 to 21.9) in 2009 to 28.4 person-years (95% CI, 27.3 to 29.5) in 2016. Similarly, the prevalence increased annually from 95.7/100,000 person-years (95% CI, 93.7 to 97.6) in 2009 to 111.0 person-years (95% CI, 108.9 to 113.2) in 2015, with a slight decrease in 2016 (110.4 person-years; 95% CI, 108.2 to 112.6). The incidence and prevalence of SPRA increased with advancing age. The peak age for both incidence and prevalence of SPRA among women of childbearing age was 40 to 44 years. Conclusions The risk of SPRA is high in women during their childbearing years; this population bears a significant disease burden. This calls for special attention to this particular population group to reduce the risk and burden of this disease.

West Nile Virus (WNV) is an arbovirus endemic to many countries and has caused over 56,000 cases, with 2776 deaths in the U.S. from 1999 to 2022. WNV occurs most often in the fall, typically affecting elderly populations in states like Nebraska and Arizona. Currently, supportive care is the only management for WNV. Our case is a female patient in her mid-70s in an intermountain state who presented in the fall with WNV meningoencephalitis and experienced a delay in care due to the unique clinical presentation. This demonstrates the importance of early inclusion of WNV in the differential for altered mental status, especially with WNV risk factors, and expedition of supportive care. Doing so could potentially reduce antibiotic duration and hospital costs.

Long-term changes in caregiver burden should be clarified considering that extended post-stroke disability can increase caregiver stress. We assessed long-term changes in caregiver burden severity and its predictors. This study was a retrospective analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Patients with an acute first-ever stroke were enrolled from August 2012 to May 2015. Data were collected at 6 months and 6 years after stroke onset. The caregiver burden was measured with a subjective caregiver burden questionnaire based on the Korean version of the Caregiver Burden Inventory. The caregivers’ characteristics and patients’ clinical and functional status were also examined at each follow-up. A high caregiver burden, which suggests a risk of burnout, was reported by 37.9% and 51.7% of caregivers at 6 months and 6 years post-stroke, respectively. Both the caregiver burden total score and proportion of caregivers at risk of burnout did not decrease between 6 months and 6 years. The patients’ disability (OR = 11.60; 95% CI 1.58–85.08; p = 0.016), caregivers’ self-rated stress (OR = 0.03; 95% CI 0.00–0.47; p = 0.013), and caregivers’ quality of life (OR = 0.76; 95% CI 0.59–0.99; p = 0.042) were burden predictors at 6 months. At 6 years, only the patients’ disability (OR = 5.88; 95% CI 2.19–15.82; p < 0.001) and caregivers’ psychosocial stress (OR = 1.26; 95% CI 1.10–1.44; p = 0.001) showed significance. Nearly half of the caregivers were at risk of burnout, which lasted for 6 years after stroke onset. The patients’ disability and caregivers’ stress were burden predictors in both subacute and chronic phases of stroke. The findings suggest that consistent interventions, such as emotional support or counseling on stress relief strategies for caregivers of stroke survivors, may reduce caregiver burden. Further research is needed to establish specific strategies appropriate for Korean caregivers to alleviate their burden in caring for stroke patients.

Background: The aim of this study was to evaluate the association of oral health status and habits with the occurrence of ankylosing spondylitis (AS) in a nationwide population-based cohort in a longitudinal setting. Methods: A total of 2,415,963 individuals aged 40–79 years who underwent oral health examinations were included from the National Health Insurance Service-National Health Screening (NHIS-HEALS) cohort of Korea between 2003 and 2004. The occurrence of AS was analyzed according to the oral health status and oral hygiene habits. Results: Among 2,271,221 of the participants, AS occurred in 6366 (0.3%) participants over 16.7 years. The likelihood of AS was higher in participants who had periodontitis (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.20–1.46, p < 0.0001) and more missing teeth (HR: 1.68, 95% CI: 1.42–1.99, p < 0.0001). However, better oral hygiene habits such as frequent tooth brushing (HR: 0.77, 95% CI: 0.71–0.83, p < 0.0001) and a history of dental scaling within the last year (HR 0.88, 95% CI 0.82–0.95, p = 0.001) were associated with a lower occurrence of AS. Conclusions: Periodontitis and an increased number of missing teeth could be related to the occurrence of late-onset AS. Improved oral hygiene care may attenuate the likelihood of late-onset AS.

This study investigates the feasibility of accurately predicting adverse health events without relying on costly data acquisition methods, such as laboratory tests, in the era of shifting healthcare paradigms towards community-based health promotion and personalized preventive healthcare through individual health risk assessments (HRAs). We assessed the incremental predictive value of four categories of predictor variables—demographic, lifestyle and family history, personal health device, and laboratory data—organized by data acquisition costs in the prediction of the risks of mortality and five chronic diseases. Machine learning methodologies were employed to develop risk prediction models, assess their predictive performance, and determine feature importance. Using data from the National Sample Cohort of the Korean National Health Insurance Service (NHIS), which includes eligibility, medical check-up, healthcare utilization, and mortality data from 2002 to 2019, our study involved 425,148 NHIS members who underwent medical check-ups between 2009 and 2012. Models using demographic, lifestyle, family history, and personal health device data, with or without laboratory data, showed comparable performance. A feature importance analysis in models excluding laboratory data highlighted modifiable lifestyle factors, which are a superior set of variables for developing health guidelines. Our findings support the practicality of precise HRAs using demographic, lifestyle, family history, and personal health device data. This approach addresses HRA barriers, particularly for healthy individuals, by eliminating the need for costly and inconvenient laboratory data collection, advancing accessible preventive health management strategies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is caused by lipid accumulation within the liver. The pathogenesis underlying its development is poorly understood. Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and a group 1 carcinogen. The aryl hydrocarbon receptor activation by B[a]P induces cytochrome P450 (CYP) enzymes, contributing to hepatic lipid accumulation. However, the molecular mechanism through which the B[a]P-mediated induction of CYP enzymes causes hepatic lipid accumulation is unknown. This research was conducted to elucidate the role of CYP1B1 in regulating B[a]P-induced lipid accumulation within hepatocytes. B[a]P increased hepatic lipid accumulation, which was mitigated by CYP1B1 knockdown. An increase in the mammalian target of rapamycin (mTOR) by B[a]P was specifically reduced by CYP1B1 knockdown. The reduction of mTOR increased the expression of autophagic flux-related genes and promoted phagolysosome formation. Both the expression and translocation of TFE3, a central regulator of lipophagy, were induced, along with the expression of lipophagy-related genes. Conversely, enhanced mTOR activity reduced TFE3 expression and translocation, which reduced the expression of lipophagy-related genes, diminished phagolysosome production, and increased lipid accumulation. Our results indicate that B[a]P-induced hepatic lipid accumulation is caused by CYP1B1-induced mTOR and the reduction of lipophagy, thereby introducing novel targets and mechanisms to provide insights for understanding B[a]P-induced MASLD.

The role of body composition parameters in sorafenib-treated hepatocellular carcinoma (HCC) patients is still not fully elucidated. Here, we aimed to evaluate the impact of computed tomography (CT)-based body composition parameters on the survival of such patients. In this multicenter study, we analyzed the data of 245 sorafenib-treated HCC patients from January 2008 to December 2019. Sarcopenia, visceral obesity, and myosteatosis were defined by using cross-sectional CT images at the third lumbar vertebra level. The effects of these parameters on overall survival (OS) and progression-free survival (PFS) were evaluated. The median age was 67.0 years (interquartile range: 61.0–78.0 year), and 211 patients (86.1%) were male. The median OS and PFS were 7.9 months and 4.8 months, respectively. Vascular invasion (hazard ratio (HR), 1.727; 95% confidence interval (CI), 1.258–2.371; p = 0.001), extrahepatic metastasis (HR, 1.401; 95% CI, 1.028–1.908; p = 0.033), alpha-fetoprotein level > 200 ng/mL (HR, 1.559; 95% CI, 1.105–2.201; p = 0.012), and myosteatosis (HR, 1.814; 95% CI, 1.112–2.960; p = 0.017) were associated with OS. Patient mortality was significantly higher in the group with two or more risk factors than in the group with fewer risk factors. In conclusion, myosteatosis may be a novel prognostic CT-based radiological biomarker in sorafenib-treated HCC patients.

IntroductionThe incidence of stroke is increasing steadily due to factors such as population aging. Approximately 80% of stroke survivors have motor disorders affecting their daily lives. Repetitive transcranial magnetic stimulation (rTMS) has been reported to maximize functional recovery after stroke along with exercise intervention in upper limb rehabilitation treatment. However, whether rTMS affects the recovery of upper limb function in patients with stroke remains unclear. Therefore, in this trial, we will investigate the efficacy of low-frequency rTMS in patients with subcortical and brainstem ischemic stroke.MethodsThis study has been designed as a multi-center, double-blind, randomized controlled trial to compare the efficacy of low-frequency rTMS over the contralesional M1 with sham stimulation. Overall, 88 participants will be allocated to the intervention or control group in a 1:1 ratio, with stratification according to their initial upper extremity Fugl-Meyer assessment (UE-FMA) score. The participants will receive either 30 min of real rTMS (intervention group) or sham rTMS (control group), followed by 30 min of occupational therapy for 10 consecutive workdays. All the participants will receive the same amount of rehabilitation therapy throughout the intervention period. Evaluations will be performed at baseline (T0), at the end of treatment (T1), and 4 weeks after the end of treatment (T2), including the box and block test (BBT), UE-FMA, Korean version of the Modified Barthel Index, and NIH Stroke Scale scores, Finger tapping test, Brunnstrom stage, modified Ashworth scale, and grip strength. The primary outcome will be the change in the BBT score between T0 and T2.ConclusionThis study will provide evidence on the efficacy of low-frequency rTMS in motor function recovery of the upper limb in patients with subacute, subcortical, and brainstem ischemic stroke.Clinical trial registrationClinicalTrials.gov, identifier [NCT05535504].

The analysis of sedimentary deposits influenced by bottom currents in glaciated continental margins provides crucial insights into paleo-depositional and oceanographic conditions. These reconstructions enable the assessment of interactions between advance and retreat of grounded ice sheets and past ocean circulation patterns. However, questions regarding these interactions and their specific mechanisms remain largely unanswered due to a lack of data in this remote area. In this study, we conducted a comprehensive analysis by integrating marine geophysical data, surficial sediment cores, oceanographic measurements, and ocean circulation models. Our aim was to understand spatial and temporal variations in sedimentary and oceanographic conditions during the past glacial and interglacial periods in combination with the long-term stratigraphic evolution. By integrating and cross-referencing diverse datasets, we were able to infer how bottom-current-controlled deposits (i.e., contourites) developed along the western bathymetric high of the Central Basin in the northwestern Ross Sea margin, Antarctica. Contouritic deposits lying over and along the flanks of bathymetric highs were identified through their mound-shaped external geometry and acoustically stratified facies, characterized by reflectors pinching toward the moat. Acoustic facies and multi-beam backscatter results, in conjunction with sedimentary core data, revealed contrasting patterns. Bathymetric highs exhibited thin (10 m thick), finer-grained stratified sediments with lower backscatter. These findings indicate that seabed winnowing occurred by strong bottom current during past glacial periods as supported by sedimentological analysis. The pathways of the westward-deflected dense shelf water outflow and the westward-flowing along-slope current, as simulated by oceanographic models, explain the distinctive development of contourites influenced by bottom-current processes. Moreover, the large accumulations of sediment in the contourites, resulting from bathymetric barriers in the north of the Central Basin, may contribute to submarine slope failures.

AimWhile the relationship between impaired kidney function and atrial fibrillation (AF) is well established, there is limited research exploring the association between elevated estimated glomerular filtration rate (eGFR) and AF development. This study aimed to examine the association between higher-than-normal eGFR and AF risk using a nationwide longitudinal study of the general population in Korea.Materials and methodsThis study utilized the National Health Insurance Service cohort database of Korea, analyzing data from 2,645,042 participants aged 20–79 years who underwent health examinations between 2010 and 2011. Participants with a history of end-stage renal disease, renal transplantation, and AF prior to the index date were excluded. Renal function was assessed using eGFR levels, calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Baseline characteristics were gathered through questionnaires, while comorbidities and AF occurrence outcomes were identified and validated using diagnostic codes and medication histories. The study employed Kaplan–Meier survival curves and Cox proportional hazard models to evaluate the association between eGFR and AF occurrence.ResultsThe mean age of subjects was 48.82 ± 10.08 years. Over a median follow-up of 9.58 years, 27,469 (1.04%) AF cases were identified. The risk for AF increased in the higher-than-normal decile, as demonstrated by Kaplan–Meier survival curves (p 120 mL/min/1.73 m2 group was associated with a decreased risk of AF [HR: 0.88, 95% CI (0.78, 0.98), p = 0.045]. Compared to the 5th decile, the 1st [HR: 1.08, 95% CI (1.03, 1.13), p = 0.010] eGFR decile was significantly associated with an increased risk of AF, while the 10th [HR: 0.77, 95% CI (0.70, 0.85), p 120 mL/min/1.73 m2 or those falling within eGFR 10th decile (>113.41 mL/min/1.73 m2) demonstrated an inverse association linked to a reduced risk of AF. Our study suggests that general population with higher-than-normal eGFR levels may have a lower risk of developing AF.

IntroductionThe influence of dietary patterns measured using Recommended Food Score (RFS) with foods with high amounts of antioxidant nutrients for Type 2 diabetes (T2D) was analyzed. Our analysis aims to find associations between dietary patterns and T2D and conduct a gene-diet interaction analysis related to T2D.MethodsData analyzed in the current study were obtained from the Korean Genome and Epidemiology Study Cohort. The dietary patterns of 46 food items were assessed using a validated food frequency questionnaire. To maximize the predictive power of the RFS, we propose two weighted food scores, namely HisCoM-RFS calculated using the novel Hierarchical Structural Component model (HisCoM) and PLSDA-RFS calculated using Partial Least Squares-Discriminant Analysis (PLS-DA) method.ResultsBoth RFS (OR: 1.11; 95% CI: 1.03- 1.20; P = 0.009) and PLSDA-RFS (OR: 1.10; 95% CI: 1.02-1.19, P = 0.011) were positively associated with T2D. Mapping of SNPs (P < 0.05) from the interaction analysis between SNPs and the food scores to genes and pathways yielded some 12 genes (CACNA2D3, RELN, DOCK2, SLIT3, CTNNA2, etc.) and pathways associated with T2D. The strongest association was observed with the adipocytokine signalling pathway, highlighting 32 genes (STAT3, MAPK10, MAPK8, IRS1, AKT1-3, ADIPOR2, etc.) most likely associated with T2D. Finally, the group of the subjects in low, intermediate and high using both the food scores and a polygenic risk score found an association between diet quality groups with issues at high genetic risk of T2D.ConclusionA dietary pattern of poor amounts of antioxidant nutrients is associated with the risk of T2D, and diet affects pathway mechanisms involved in developing T2D.

IntroductionUpfront autologous stem cell transplantation (ASCT) has been recommended for patients who are newly diagnosed with peripheral T-cell lymphoma (PTCL), and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), an anthracycline-based chemotherapy has been the frontline chemotherapy for PTCL. However, it is not clear whether anthracycline-based chemotherapies such as CHOP could be standard induction therapy for PTCL.MethodsWe conducted a randomized phase II study to compare CHOP with fractionated ifosfamide, carboplatin, etoposide, and dexamethasone (ICED) for patients eligible for ASCT. The primary endpoint was progression-free survival (PFS) and secondary endpoints included objective response rate, overall survival (OS), and safety profiles.ResultsPatients were randomized into either CHOP (n = 69) or ICED (n = 66), and the characteristics of both arms were not different. PTCL-not otherwise specified (NOS, n = 60) and angioimmunoblastic T-cell lymphoma (AITL, n = 53) were dominant. The objective response rate was not different between CHOP (59.4%) and ICED (56.1%), and the 3-year PFS was not different between CHOP (36.7%) and ICED (33.1%). In AITL patients, CHOP was favored over ICED whereas ICED was associated with more cytopenia and reduced dose intensity. Patients who received upfront ASCT after achieving complete response to CHOP or ICED showed 80% of 3-year OS.DiscussionIn summary, our study showed no therapeutic difference between CHOP and ICED in terms of response and PFS. Thus, CHOP might remain the reference regimen especially for AITL based on its better outcome in AITL, and upfront ASCT could be recommended as a consolidation of complete response in patients with PTCL.

Abstract The immense increase of unstructured data require novel computing systems that can process the input data with low power and parallel processing. This functionality is similar to that of human brains that are composed of numerous neurons, synapses, and their complex connections. To mimic the functionality of the human brain with an electronic device, the resistive switching device and crossbar array has attracted considerable attention for artificial synaptic devices and integrated systems, respectively. For this purpose, the self‐rectifying resistive switching cell based on the Si:ZrOx thin film is developed and its reliability characteristics are tested. Four achievements are highlighted in this study. 1) The retention characteristic is improved by the adoption of TaOx thin film as an oxygen reservoir layer. 2) The asymmetric electrodes can make the self‐rectifying resistive cell (SRC) have sufficient rectifying characteristic. 3) The linearity of conductance update has a dominant effect on the inference performance compared to that of the conductance range variation. 4) The device of the interface‐type resistive switching shows a high enough device yield in the crossbar array device and exhibits reliable multiply‐and‐accumulate operations in the crossbar array to mimic the human brain‐inspired computing system.

Metallic glasses (MGs) have garnered significant attention for the possibility to use as advanced structural materials in recent decades. However, their high processing costs remain a major obstacle to their commercialization. This research offers a practical guideline to significantly reduce production costs through tailored alloy design and precise control of thermoplastic forming (TPF) process parameters. Specifically, we discovered commercially available MGs with a low glass transition temperature (Tg) can be developed in the Zr-rich alloy systems. Moreover, we addressed the challenge of maintaining a wide TPF window in Be-free Zr-based MGs while keeping Tg low. Our research has yielded the development of Be-free Zr-rich multicomponent MGs with a low Tg below 350 °C (623 K) and a wide TPF window of over 70 K, resulting in excellent thermoplastic formability (TPFA). Notably, the MGs we developed exhibit a lower Tg than advanced engineering plastics like Polyimide and Polybenzimidazole, which suggests that the TPF process of plastics could be extended to MGs. In addition, we employed Flash-DSC to accurately identify the TPF window and TPFA according to the heating rate in a wide range from 10-1 to 104 K/s, and proposed novel TPFA parameters that are based on continuous heating transformation diagram with iso-viscosity contours. Our findings demonstrate that even marginal MGs have a significant advantage in manufacturing micro-to-nano scale products that can be molded at ultra-fast heating rates, similar to advanced engineering plastics. Indeed, this work will undoubtedly inspire us to further explore the potential of MGs as a practical material for industrial applications.

Summary: Background: Early diagnosis and appropriate treatment are essential in meningitis and encephalitis management. We aimed to implement and verify an artificial intelligence (AI) model for early aetiological determination of patients with encephalitis and meningitis, and identify important variables in the classification process. Methods: In this retrospective observational study, patients older than 18 years old with meningitis or encephalitis at two centres in South Korea were enrolled for development (n = 283) and external validation (n = 220) of AI models, respectively. Their clinical variables within 24 h after admission were used for the multi-classification of four aetiologies including autoimmunity, bacteria, virus, and tuberculosis. The aetiology was determined based on the laboratory test results of cerebrospinal fluid conducted during hospitalization. Model performance was assessed using classification metrics, including the area under the receiver operating characteristic curve (AUROC), recall, precision, accuracy, and F1 score. Comparisons were performed between the AI model and three clinicians with varying neurology experience. Several techniques (eg, Shapley values, F score, permutation feature importance, and local interpretable model-agnostic explanations weights) were used for the explainability of the AI model. Findings: Between January 1, 2006, and June 30, 2021, 283 patients were enrolled in the training/test dataset. An ensemble model with extreme gradient boosting and TabNet showed the best performance among the eight AI models with various settings in the external validation dataset (n = 220); accuracy, 0.8909; precision, 0.8987; recall, 0.8909; F1 score, 0.8948; AUROC, 0.9163. The AI model outperformed all clinicians who achieved a maximum F1 score of 0.7582, by demonstrating a performance of F1 score greater than 0.9264. Interpretation: This is the first multiclass classification study for the early determination of the aetiology of meningitis and encephalitis based on the initial 24-h data using an AI model, which showed high performance metrics. Future studies can improve upon this model by securing and inputting time-series variables and setting various features about patients, and including a survival analysis for prognosis prediction. Funding: MD-PhD/Medical Scientist Training Program through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea.

BackgroundHighly personalized care is substantially improved by technology platforms that assess and track patient outcomes. However, evidence regarding how to successfully implement technology in real-world mental health settings is limited. ObjectiveThis study aimed to naturalistically monitor how a health information technology (HIT) platform was used within 2 real-world mental health service settings to gain practical insights into how HIT can be implemented and sustained to improve mental health service delivery. MethodsAn HIT (The Innowell Platform) was naturally implemented in 2 youth mental health services in Sydney, Australia. Web-based surveys (n=19) and implementation logs were used to investigate staff attitudes toward technology before and after implementation. Descriptive statistics were used to track staff attitudes over time, whereas qualitative thematic analysis was used to explore implementation log data to gain practical insights into useful implementation strategies in real-world settings. ResultsAfter the implementation, the staff were nearly 3 times more likely to agree that the HIT would improve care for their clients (3/12, 25% agreed before the implementation compared with 7/10, 70% after the implementation). Despite this, there was also an increase in the number of staff who disagreed that the HIT would improve care (from 1/12, 8% to 2/10, 20%). There was also decreased uncertainty (from 6/12, 50% to 3/10, 30%) about the willingness of the service to implement the technology for its intended purpose, with similar increases in the number of staff who agreed and disagreed with this statement. Staff were more likely to be uncertain about whether colleagues in my service are receptive to changes in clinical processes (not sure rose from 5/12, 42% to 7/10, 70%). They were also more likely to report that their service already provides the best mental health care (agreement rose from 7/12, 58% to 8/10, 80%). After the implementation, a greater proportion of participants reported that the HIT enabled shared or collaborative decision-making with young people (2/10, 20%, compared with 1/12, 8%), enabled clients to proactively work on their mental health care through digital technologies (3/10, 30%, compared with 2/12, 16%), and improved their response to suicidal risk (4/10, 40% compared with 3/12, 25%). ConclusionsThis study raises important questions about why clinicians, who have the same training and support in using technology, develop more polarized opinions on its usefulness after implementation. It seems that the uptake of HIT is heavily influenced by a clinician’s underlying beliefs and attitudes toward clinical practice in general as well as the role of technology, rather than their knowledge or the ease of use of the HIT in question.

As the emergence and prevalence of antibiotic-resistant strains have resulted in a global crisis, there is an urgent need for new antimicrobial agents. Antimicrobial peptides (AMPs) exhibit inhibitory activity against a wide spectrum of pathogens and can be utilized as an alternative to conventional antibiotics. In this study, two novel AMPs were identified from the venom transcriptome of the spider Argiope bruennichi (Scopoli, 1772) using in silico methods, and their antimicrobial activity was experimentally validated. Aranetoxin-Ab2a (AATX-Ab2a) and Aranetoxin-Ab3a (AATX-Ab3a) were identified by homology analysis and were predicted to have high levels of antimicrobial activity based on in silico analysis. Both peptides were found to have antibacterial effect against Gram-positive and -negative strains, and, in particular, showed significant inhibitory activity against multidrug-resistant Pseudomonas aeruginosa isolates. In addition, AATX-Ab2a and AATX-Ab3a inhibited animal and vegetable fungal strains, while showing low toxicity to normal human cells. The antimicrobial activity of the peptides was attributed to the increased permeability of microbial membranes. The study described the discovery of novel antibiotic candidates, AATX-Ab2a and AATX-Ab3a, using the spider venom gland transcriptome, and validated an in silico-based method for identifying functional substances from biological resources.

IntroductionLong-term care hospitals are known to be vulnerable to SARS-CoV-2 infection and death given their numerous older chronic disease patients. However, the actual effect of long-term care hospital admission is not well known in Korea; hence, this study sought to analyze the effect of long-term care hospitalization on SARS-CoV-2 infection and COVID-19 death by correcting for patients’ characteristics.MethodsThis cross-sectional study used the data from K-COV-N cohort, which is linked to the National Health Insurance Service and the Korea Disease Control and Prevention Agency; it analyzed 70,373 individuals aged ≥60 years, who had been tested for COVID-19 between January 1 and May 30, 2020 (KDCA-NHIS-2020-1-601). Patients admitted to a long-term care hospital were defined as those with a confirmed history of hospitalization within 30 days of the COVID-19 testing date. The final data analysis was performed in December 2022. Logistic regression analysis of the national data was employed to determine the association between long-term care hospital admission, the risk of SARS-CoV-2 infection, and death from COVID-19. The odds ratios for SARS-CoV-2 infection and death from COVID-19 were calculated by adjusting for sex, age, residential area, health insurance premium, disability, and the Charlson Comorbidity Index.ResultsOlder patients at long-term care hospitals had a high risk of SARS-CoV-2 infection (OR:2.91, 95% CI:2.33–3.64) and death from COVID-19 (OR:3.58, 95% CI:2.13–6.02). A difference in SARS-CoV-2 infection risk was observed based on residential area, health insurance premium (economic level), and disability; no difference was observed for COVID-19 mortality risk.DiscussionAdmission to a long-term care hospital itself could be a risk factor for SARS-CoV-2 infection and the consequent high mortality risk after adjusting for sex, age, disability, and comorbidities. Patients are at high risk of infection through contact with workers, leading to death; therefore, quarantine policies for workers must be strengthened.

Abstract In the upcoming ubiquitous era, wearable/flexible electronics are spotlighted to get various types of numerous information in real time. Several researchers have investigated flexible materials, and developed diverse thin‐film transfer methods. However, there are some limitations of the intrinsic material unstabilities, and low production yield. Here, light‐induced thin‐film transfer methods are reported by using new transfer mechanism of phase transition in sacrificial materials. Lift‐off conditions with high‐energy laser are delicately optimized by theoretical calculations and experiments to minimize mechanical/thermal damages of the upper thin‐film devices. The selected sacrificial materials of GeSbTe (GST) and indium tin oxide (ITO) with the 300 nm thickness are delaminated from a transparent and rigid glass substrate by irradiating the excimer laser to the surface of the sacrificial layer. The laser‐based exfoliation mechanism of GST and ITO films are comprehended by various material surface analyses. Eventually, flexible oxide thin‐film transistors (TFTs) are successfully demonstrated through light‐induced exfoliation process, showing the usability of the developed transfer technique to future practical applications.

IntroductionWhile accessing the posterior fossa, the anterior transpetrosal approach (ATPA) and endoscopic transorbital approach (ETOA) use the same bony landmarks during petrous apex drilling. However, owing to their contrasting surgical axes, they are expected to show differences in surgical view, maneuverability, and clinical implications. This study aimed to investigate the feasibility of ETOA in accessing the brainstem and to compare the surgical view and maneuverability of each approach.MethodsATPA and ETOA were performed in four human cadaveric heads (eight sides and four sides in each procedure). The angle of attack (AOA) and surgical depth were measured at the target of interest (root exit zone [REZ] of cranial nerve [CN] V, VI, and VII). When measuring the area of exposure, the brainstem was divided into two areas (anterior and lateral brainstem) based on the longitudinal line crossing the entry zone of the trigeminal root, and the area of each was measured.ResultsATPA showed significantly greater value at the trigeminal REZ in both vertical (31.8 ± 6.7° vs. 14.3 ± 5.3°, p=0.006) and horizontal AOA (48.5 ± 2.9° vs. 15.0 ± 5.2°, p

Abstract The clinical progression of neurodegenerative diseases correlates with the spread of proteinopathy in the brain. The current understanding of the mechanism of proteinopathy spread is far from complete. Here, we propose that inflammation is fundamental to proteinopathy spread. A sequence variant of α-synuclein (V40G) was much less capable of fibril formation than wild-type α-synuclein (WT-syn) and, when mixed with WT-syn, interfered with its fibrillation. However, when V40G was injected intracerebrally into mice, it induced aggregate spreading even more effectively than WT-syn. Aggregate spreading was preceded by sustained microgliosis and inflammatory responses, which were more robust with V40G than with WT-syn. Oral administration of an anti-inflammatory agent suppressed aggregate spreading, inflammation, and behavioral deficits in mice. Furthermore, exposure of cells to inflammatory cytokines increased the cell-to-cell propagation of α-synuclein. These results suggest that the inflammatory microenvironment is the major driver of the spread of synucleinopathy in the brain.

Abstract This study was conducted to identify fall injury patterns, the transition from the baseline to follow-up, and the factors associated with the identified fall injury patterns using data obtained from the Korean Frailty and Aging Cohort Study. The participants were 566 community-dwelling older adults with fall experience. Three fall injury patterns were identified as the baseline and follow-up periods. The probability that the participant in the “fracture injury” pattern at Time 1 transitioned to the “fracture injury” pattern at Time 2 was 0.098. The factors associated with the “bruising and/or sprain injury” pattern were education level (relative risk ratio [RRR] = 0.55, p = 0.012), alcohol consumption (RRR = 0.50, p = 0.034), and balancing in tandem position (RRR = 2.77, p

Abstract This study aimed to assess the performance of deep learning (DL) algorithms in the diagnosis of nasal bone fractures on radiographs and compare it with that of experienced radiologists. In this retrospective study, 6713 patients whose nasal radiographs were examined for suspected nasal bone fractures between January 2009 and October 2020 were assessed. Our dataset was randomly split into training (n = 4325), validation (n = 481), and internal test (n = 1250) sets; a separate external dataset (n = 102) was used. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of the DL algorithm and the two radiologists were compared. The AUCs of the DL algorithm for the internal and external test sets were 0.85 (95% CI, 0.83–0.86) and 0.86 (95% CI, 0.78–0.93), respectively, and those of the two radiologists for the external test set were 0.80 (95% CI, 0.73–0.87) and 0.75 (95% CI, 0.68–0.82). The DL algorithm therefore significantly exceeded radiologist 2 (P = 0.021) but did not significantly differ from radiologist 1 (P = 0.142). The sensitivity and specificity of the DL algorithm were 83.1% (95% CI, 71.2–93.2%) and 83.7% (95% CI, 69.8–93.0%), respectively. Our DL algorithm performs comparably to experienced radiologists in diagnosing nasal bone fractures on radiographs.

Multiple sclerosis is a debilitating autoimmune disease, for which therapy is not curative, only slowing down progression at the expense of general immune suppression. Here authors show that in a mouse model of multiple sclerosis, disease progression could be halted or even reversed by a nanovaccine, composed of reactive oxygen species scavenging cerium oxide nanoparticles, which establishes immune tolerance against the relevant autoantigen.

Background: Low muscle mass, or sarcopenia, predicts poorer treatment outcomes in breast cancer. Neoadjuvant chemotherapy is the main treatment to improve surgical outcomes for breast cancer, yet few studies have assessed the relationships between different chemotherapy regimens and sarcopenia. This study compared body composition change between two neoadjuvant chemotherapy regimens: AC-T (anthracyclines and cyclophosphamide followed by a taxane) and TCHP (docetaxel, carboplatin, trastuzumab, and pertuzumab). Methods: This study included 298 patients with breast cancer who received neoadjuvant chemotherapy between 2017 and 2020 at one university hospital. Body composition was assessed by computed tomography. Multiple linear regression was performed to examine predictors of SMI change. Results: Patients receiving TCHP showed a significant mean skeletal muscle index (SMI) decrease of 1.6 cm2/m2 (SD = 3.5, p

Diabetes screening serves to identify individuals at high-risk for diabetes who have not yet developed symptoms and to diagnose diabetes at an early stage. Globally, the prevalence of diabetes is rapidly increasing. Furthermore, obesity and/or abdominal obesity, which are major risk factors for type 2 diabetes mellitus (T2DM), are progressively increasing, particularly among young adults. Many patients with T2DM are asymptomatic and can accompany various complications at the time of diagnosis, as well as chronic complications develop as the duration of diabetes increases. Thus, proper screening and early diagnosis are essential for diabetes care. Based on reports on the changing epidemiology of diabetes and obesity in Korea, as well as growing evidence from new national cohort studies on diabetes screening, the Korean Diabetes Association has updated its clinical practice recommendations regarding T2DM screening. Diabetes screening is now recommended in adults aged ≥35 years regardless of the presence of risk factors, and in all adults (aged ≥19) with any of the risk factors. Abdominal obesity based on waist circumference (men ≥90 cm, women ≥85 cm) was added to the list of risk factors.

Abstract The International Myeloma Working Group has recently revised the diagnostic criteria for primary plasma cell leukemia (PCL) to circulating plasma cells (CPCs) ≥ 5% in a peripheral blood smear. The present study validated new criteria in patients with multiple myeloma or PCL diagnosed using the previous diagnostic criteria, who were administered immunomodulatory drugs or proteasome inhibitors as induction therapy. We analyzed the medical records of 1357 patients from eight hospitals in South Korea. The median age of the all patients was 64 years, and 187 (13.8%) had CPCs at diagnosis. Only 79 (5.8%) of the patients had ≥ 5% CPCs. The median overall survival (OS) of patients with CPCs ≥ 5% and ≥ 20% was similar, but had significantly inferior median progression-free survival (PFS) and median OS than those with CPCs < 5% (13.1 vs. 21.5 months, P

Background/Aims We aimed to estimate the prevalence of comorbidities and medication use in Korean women with rheumatic diseases (RDs) during their childbearing years. Methods We included women aged 20 to 44 years with seropositive rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) (n = 41,547) and age-matched women without seropositive RA, SLE, and AS (n = 208,941) from the National Health Insurance Service-National Health Information Database (2009 to 2016). The prevalence of hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), and cancer and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids (CSs), and disease-modifying anti-rheumatic drugs (DMARDs) were estimated. Results Women of childbearing age with RDs were more likely to have at least one of the measured comorbidities than the controls (odds ratio [OR], 3.0; 95% confidence interval [CI], 2.9 to 3.1). The OR (95% CI) was 2.9 (2.8 to 3.0) for HTN, 2.8 (2.7 to 2.9) for HLD, 1.4 (1.4 to 1.5) for DM, and 1.3 (1.3 to 1.4) for cancer. The SLE group had the highest prevalence and odds of all four measured comorbidities. Almost all (97.9%) women of childbearing age with RDs were taking RD-related medications (NSAIDs, 81.6%; CSs, 77.8%; DMARDs, 87.3%). The RD group was 13.8 times more likely to take NSAIDs and 68.2 times more likely to take CSs than the controls. Use of NSAIDs was more prevalent in RA and AS than SLE, whereas use of CSs and DMARDs was more prevalent in RA and SLE than AS. Conclusions Korean women with RDs have a greater burden of comorbidities and medication use during their childbearing years than women without RDs of the same age.

Abstract Association between exposure to periodontal bacteria and development of autoantibodies related to rheumatoid arthritis (RA) has been widely accepted; however, direct causal relationship between periodontal bacteria and rheumatoid factor (RF) is currently not fully understood. We investigated whether periodontal bacteria could affect RF status. Patients with preclinical, new-onset, or chronic RA underwent periodontal examination, and investigation of subgingival microbiome via 16S rRNA sequencing. Degree of arthritis and RF induction was examined in collagen-induced arthritis (CIA) mice that were orally inoculated with different periodontal bacteria species. Subsequently, single-cell RNA sequencing analysis of the mouse spleen cells was performed. Patients with preclinical RA showed an increased abundance of the Porphyromonadacae family in the subgingival microbiome compared to those with new-onset or chronic RA, despite comparable periodontitis severity among them. Notably, a distinct subgingival microbial community was found between patients with high-positive RF and those with negative or low-positive RF (p=0.022). Oral infections with the periodontal pathogens P. gingivalis and Treponema denticola in CIA mice similarly enhanced arthritis score, but resulted in different levels of RF induction. Genes related to B cell receptor signaling, B cell proliferation, activation, and differentiation, and CD4+ T cell costimulation and cytokine production were involved in the differential induction of RF in mice exposed to different bacteria. In summary, periodontal microbiome might shape RF status by affecting the humoral immune response during RA pathogenesis.

Abstract Biliary strictures can have several benign or malignant causes. We attempted to determine the usefulness of establishing a diagnosis using self-expandable metal stents (SEMS) in a prospective series of patients with suspected malignant biliary obstruction. Data of patients who underwent SEMS removal from August 2016 to December 2019 were collected. During this period, 55 patients underwent endobiliary biopsy and SEMS insertion and removal. Fifty-five consecutive patients (mean age, 69 years; range 53–90 years) were enrolled, and of these, 37 were male and 18 were female. A final diagnosis was established using biopsy specimens in 37 cases (67.3%) and surgical specimens in 6 cases (10.9%), with 12 cases (21.8%) diagnosed on radiological follow-up. The final diagnoses included malignancy in 34 cases (61.8%) and benign stricture in 21 cases (38.2%). Endobiliary biopsy had a sensitivity and specificity of 44.1% and 95.2%, whereas SEMS cytology had a sensitivity and specificity of 52.9% and 100%, respectively. Combining endobiliary biopsy and/or SEMS cytology yielded a sensitivity and specificity of 73.5% and 95.2%, respectively. (1) The use of biopsy results alone as a diagnostic tool yielded an area under the receiver operating characteristic curve (AUC) of 0.70 (0.60–0.79). (2) The addition of SEMS to the biopsy results yielded an AUC of 0.86 (0.78–0.94). (3) The addition of CA 19–9 levels to the biopsy results yielded an AUC of 0.81 (0.71–0.94). (4) Combining the endobiliary biopsy results, SEMS tissues, and CA 19–9 levels yielded the best diagnostic accuracy, with an AUC of 0.90 (0.83–0.98). Detection of biliary obstruction using the combination strategy was better than the diagnostic results based on biopsy alone according to recent 3-year data. Our study suggested that SEMS removal could help establish a diagnosis of suspected malignant biliary obstruction.

Background/Aims Gastrointestinal bleeding (GIB) risk for non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin is largely unknown. We aimed to determine the risk of overall and post-polypectomy GIB for NOACs and warfarin. Methods Using the Korean National Health Insurance database, we created a cohort of patients who were newly prescribed NOACs or warfarin between July 2015 and December 2017 using propensity score matching (PSM). Kaplan-Meier analysis with log-rank test was performed to compare the risk of overall and post-polypectomy GIB between NOACs (apixaban, dabigatran, and rivaroxaban) and warfarin. Post-polypectomy GIB was defined as bleeding within 1 month after gastrointestinal endoscopic polypectomy. Results Out of 234,206 patients taking anticoagulants (187,687 NOACs and 46,519 warfarin), we selected 39,764 pairs of NOACs and warfarin users after PSM. NOACs patients showed significantly lower risk of overall GIB than warfarin patients (log-rank P

Background An accurate diagnosis in patients with interstitial lung diseases (ILDs) by multidisciplinary discussion (MDD) based on histopathologic information is essential for optimal treatment. Transbronchial lung cryobiopsy (TBLC) has increasingly been used as a diagnostic alternative to surgical lung biopsy. This study aimed to evaluate the appropriate methods of TBLC in patients with ILD in Korea. Methods A total of 27 patients who underwent TBLC were included. TBLC procedure details and clinical MDD diagnosis using TBLC histopathologic information were retrospectively analyzed. Results All procedures were performed under general anesthesia with the fluoroscopic guidance in the operation room using flexible bronchoscopy and endobronchial balloon blocker. The median procedure duration was less than 30 minutes, and the median number of biopsies per participant was 2. Most of the bleeding after TBLC was not severe, and the rate of pneumothorax was 25.9%. The most common histopathologic pattern was alternative (48.2%), followed by indeterminate (33.3%) and usual interstitial pneumonia (UIP)/probable UIP (18.5%). In the MDD after TBLC, the most common diagnosis was idiopathic pulmonary fibrosis (33.3%), followed by smoking-related ILD (25.9%), nonspecific interstitial pneumonia (18.6%), unclassifiable-ILD (14.8%), and others (7.4%). Conclusion This first single-center experience showed that TBLC using a flexible bronchoscopy and endobronchial balloon blocker with the fluoroscopic guidance under general anesthesia may be a safe and adequate diagnostic method for ILD patients in Korea. The diagnostic yield of MDD was 85.2%. Further studies are needed to evaluate the diagnostic yield and confidence of TBLC.

Abstract Background Various cancer stem cell (CSC) biomarkers and the genes encoding them in head and neck squamous cell carcinoma (HNSCC) have been identified and evaluated. However, the validity of these factors in the prognosis of HNSCC has been questioned and remains unclear. In this study, we examined the clinical significance of CSC biomarker genes in HNSCC, using five publicly available HNSCC cohorts. Methods To predict the prognosis of patients with HNSCC, we developed and validated the expression signatures of CSC biomarker genes whose mRNA expression levels correlated with at least one of the four CSC genes (CD44, MET, ALDH1A1, and BMI1). Results Patients in The Cancer Genome Atlas (TCGA) HNSCC cohort were classified into CSC gene expression-associated high-risk (CSC-HR; n = 285) and CSC gene expression-associated low-risk (CSC-LR; n = 281) subgroups. The 5-year overall survival and recurrence-free survival rates were significantly lower in the CSC-HR subgroup than in the CSC-LR subgroup (p = 0.04 and 0.02, respectively). The clinical significance of the CSC gene expression signature was validated using four independent cohorts. Analysis using Cox proportional hazards models showed that the CSC gene expression signature was an independent prognostic factor of non-oropharyngeal HNSCC which mostly indicates HPV (–) status. Furthermore, the CSC gene expression signature was associated with the prognosis of HNSCC patients who received radiotherapy. Conclusion The CSC gene expression signature is associated with the prognosis of HNSCC and may help in personalized treatments for patients with HNSCC, especially in cases with HPV (–) status who were classified in more detail.

Abstract Background As the life expectancy of people living with HIV increases with the advancements in antiretroviral treatment, the continuity of long-term therapy and health care for people living with HIV has gained more importance. However, the estimated proportion of people living with HIV who have access to treatment or are virally suppressed is unsatisfactory. Therefore, it is necessary to build strategies to improve treatment continuity by identifying the barriers and facilitators that affect the HIV care continuum. To enable this, we will conduct a scoping review to explore the barriers and facilitators related to the care continuum in high-income countries for adults living with HIV. Methods The review question will be identified based on the JBI guidelines for the development of scoping review protocols. Studies exploring the barriers to and facilitators of the HIV care continuum among adults living with HIV in high-income countries will be included in this review. A literature search will be conducted on the databases (platform) of MEDLINE (Ovid), Cumulative Index to Nursing and Allied Health Literature (EBSCO), Embase (Ovid), and the Cochrane Central Register of Controlled Trials (Cochrane Library). Four researchers will screen articles for inclusion and subsequently build a charting form and collate the data to provide results. Discussion The results of this scoping review will provide comprehensive evidence for the barriers and facilitators to be considered in the care continuum of people living with HIV. Importantly, the results will provide insight for healthcare providers and researchers to develop interventions and research the continuity in caring for people living with HIV.

Abstract Boron neutron capture therapy (BNCT) has been attracting interest as a new radiation modality for cancer therapy because it can selectively destroy cancer cells while maintaining the healthy state of surrounding normal cells. Many experimental trials have demonstrated significant BNCT treatment efficacy using neutron beams from research reactors. However, nuclear reactor technology cannot be scaled to sites in hospitals delivering patient treatment. Therefore, compact accelerator-based neutron sources that could be installed in many hospitals are under development or have even been commissioned at many facilities around the world. In Korea, a radio-frequency (RF) linac-based BNCT (A-BNCT) facility is under development by DawonMedax (DM). It provides the highly efficient production of an epithermal neutron beam with an optimized neutron energy spectrum range of 0.1~10 keV. With a 2-mA 10-MeV proton beam from the accelerator, the irradiation port epithermal neutron flux is higher than 1 × 109 n/cm2⋅s. Comprehensive verification and validation of the system have been conducted with the measurement of both proton and neutron beam characteristics. Significant therapeutic effects from BNCT have been confirmed by DM in both in vitro and in vivo non-clinical trials. Further, during exposure to epithermal neutrons, all other unintended radiation is controlled to levels meeting International Atomic Energy Agency (IAEA) recommendations. Recently, the Korean FDA has accepted an investigational new drug (IND) and the first-in-human clinical trial of BNCT is now being prepared. This paper introduces the principles of BNCT and accelerator-based neutron sources for BNCT and reports the recent advances of DM A-BNCT facility which is the main part of this paper.

Byline: Jae-Hyeok. Heo, Min-Ky. Kim, Jun-Hyung. Lee, Jeong-Heon. Lee Background: The Korean version of Mini-Mental Status Examination (K-MMSE) and the Korean version of Addenbrooke Cognitive Examination (K-ACE) have been validated [...]