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We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, –0.02 mL/min/1.73 m2 [95% confidence interval (CI), –3.87 to 3.83 mL/min/1.73 m2] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m2 [95% CI, 3.16 to 10.46 mL/min/1.73 m2]; P

The chief goal of the Blood Profiling Atlas in Cancer (BloodPAC) consortium is to promote collaborative efforts that support the development and implementation of liquid biopsy tests. Here, we report the results of a pilot study conducted by three BloodPAC members that aimed to demonstrate a multisite liquid biopsy testing framework using longitudinal blood specimens from 38 patients with metastatic breast cancer. Three laboratories receiving identical samples from two clinical sites each applied a different targeted sequencing platform to analyze mutations in cell-free DNA (cfDNA). The resulting mutational profiles reflected common breast cancer alterations, including clinically actionable mutations for 40% of hormone- receptor-positive patients. In 12 genes with shared target regions across sequencing panels, perfect inter-assay concordance was also observed for mutations detected above the lowest common assay limit of detection. Whole-genome copy number profiling of cfDNA and circulating tumor cells (CTCs) further revealed marked heterogeneity in copy number alterations and cfDNA tumor fractions across patients. Additionally, comparison of tumor fraction and CTC abundance demonstrated the complementary nature of cfDNA and CTC analyses. Overall, the framework described in this study may serve as a resource for future trials aiming to identify multimodal liquid biopsy biomarkers to guide clinical care.

Abstract Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10–15 and 4.84 × 10–10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10–4, and 7.15 × 10–4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10–8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351–1.700), 1.43 × 10–12 and MD-MAFLD: 1.300 (1.191–1.416), 2.90 × 10–9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10–8 and 1.225 (1.122, 1.340), 7.06 × 10–6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.

Purpose To develop models to predict programmed death ligand 1 (PD-L1) expression in pulmonary squamous cell carcinoma (SCC) using CT. Materials and Methods A total of 97 patients diagnosed with SCC who underwent PD-L1 expression assay were included in this study. We performed a CT analysis of the tumors using pretreatment CT images. Multiple logistic regression models were constructed to predict PD-L1 positivity in the total patient group and in the 40 advanced-stage (≥ stage IIIB) patients. The area under the receiver operating characteristic curve (AUC) was calculated for each model. Results For the total patient group, the AUC of the ‘total significant features model’ (tumor stage, tumor size, pleural nodularity, and lung metastasis) was 0.652, and that of the ‘selected feature model’ (pleural nodularity) was 0.556. For advanced-stage patients, the AUC of the ‘selected feature model’ (tumor size, pleural nodularity, pulmonary oligometastases, and absence of interstitial lung disease) was 0.897. Among these factors, pleural nodularity and pulmonary oligometastases had the highest odds ratios (8.78 and 16.35, respectively). Conclusion Our model could predict PD-L1 expression in patients with lung SCC, and pleural nodularity and pulmonary oligometastases were notable predictive CT features of PD-L1.

Conflicting findings have been reported regarding the association between Agent Orange (AO) exposure and type 2 diabetes. This study aimed to examine whether AO exposure is associated with the development of type 2 diabetes and to verify the causal relationship between AO exposure and type 2 diabetes by combining DNA methylation with DNA genotype analyses. An epigenome-wide association study and DNA genotype analyses of the blood of AO-exposed and AO-unexposed individuals with type 2 diabetes and that of healthy controls were performed. Methylation quantitative trait locus and Mendelian randomisation analyses were performed to evaluate the causal effect of AO-exposure-identified CpGs on type 2 diabetes. AO-exposed individuals with type 2 diabetes were associated with six hypermethylated CpG sites (cg20075319, cg21757266, cg05203217, cg20102280, cg26081717, and cg21878650) and one hypo-methylated CpG site (cg07553761). Methylation quantitative trait locus analysis showed the methylation levels of some CpG sites (cg20075319, cg20102280, and cg26081717) to be significantly different. Mendelian randomisation analysis showed that CpG sites that were differentially methylated in AO-exposed individuals were causally associated with type 2 diabetes; the reverse causal effect was not significant. These findings reflect the need for further epigenetic studies on the causal relationship between AO exposure and type 2 diabetes.

This study aims to address a research gap concerning valid and reliable analytic rubrics for assessing students’ performance on Model-Eliciting Activities (MEAs), an extensively researched category of well-structured modeling activities, with a specific focus on evaluating creativity–a fundamental element in engineering–in a consistent and transparent manner. In this empirical study, we present the design and validation process for an analytic rubric intended to assess the cybersecurity problem-solving skills and creativity of engineering students in computer science courses. To gauge the reliability of the rubric, a statistical method was used to measure consistency and agreement among four raters when evaluating the performance of 28 undergraduates on the Cipher Algorithm MEA by using the analytic rubric, specifically in terms of cybersecurity problem-solving and creativity. The results demonstrate a good overall level of inter-rater agreement across the evaluation criteria and illustrate how the analytic rubric with the MEA can be used consistently and transparently to assess the cybersecurity problem-solving skills and creativity of engineering students. Our analytic rubric, designed to address challenges in assessing and grading modeling problems, is expected to contribute by providing a demonstration for instructors interested in incorporating MEAs into their toolkit, aiming to enhance conceptual understanding, problem-solving skills, and creativity in students and facilitate formative assessments that offer precise feedback for improvement across various performance areas.

Background: Fluoroscopy-guided PTNB for fluoroscopy-identifiable lung lesions has been suggested as a useful method for the pathological diagnosis of lung lesions; however, it is lacking in accuracy and safety compared to CT-guided PTNB. Thus, we aimed to investigate the diagnostic accuracy and complications of fluoroscopy-guided percutaneous transthoracic needle biopsy (PTNB) with the aid of pre-procedural planning cone-beam computed tomography (CBCT) in order to take advantage of their respective strengths. Methods: A total of 255 fluoroscopy-guided PTNBs with the aid of planning CBCT were performed. Pre-procedural planning CBCT was conducted to calculate the shortest length from the skin puncture site to the margin of the target lesion for the needle trajectory. No intra-procedural CBCT was performed. The diagnostic performance of fluoroscopy-guided PTNB with the aid of planning CBCT was calculated. The prognostic factors for diagnostic failures and complications were evaluated using logistic regression analysis. Results: The accuracy, sensitivity, specificity, PPV, and NPV were 97.3%, 88.0%, 90.9%, 100%, and 62.5%, respectively. There were 29 diagnostic failures (11.8%), and the multivariable analysis showed that a longer lesion depth on CBCT and a shorter specimen length were each associated with diagnostic failure (p = 0.010 and 0.012, respectively). Complications occurred in 34 PTNBs (13.3%). The multivariable analysis showed that an increased total number of biopsies per lesion, a longer length of lung aeration via needle insertion, a smaller lesion size on CT imaging (≤20 mm), and the presence of an air bronchogram were associated with the occurrence of complications (p = 0.027, Conclusions: Excellent diagnostic accuracy was obtained by fluoroscopy-guided PTNB with the aid of planning CBCT. Compared to that of CT- or CBCT-guided PTNB, the procedure-related complication rate was acceptably low, but the radiation dose to patients could be potentially reduced.

Background/Objectives: We aimed to investigate the genetic loci related to disc hemorrhage (DH) and the relationship of causation between DH and primary open-angle glaucoma (POAG) using a genome-wide association study (GWAS) in East Asian individuals. Methods: The GWAS included 8488 Koreans who underwent ocular examination including fundus photography to determine the presence of DH and POAG. We performed a GWAS to identify significant single-nucleotide polymorphisms (SNPs) associated with DH and analyzed the heritability of DH and genetic correlation between DH and POAG. The identified SNPs were utilized as instrumental variables (IVs) for two-sample Mendelian randomization (MR) analysis. The POAG outcome dataset was adopted from Biobank Japan data (n = 179,351). Results: We found that the rs62463744 (TMEM270;ELN), rs11658281 (CCDC42), and rs77127203 (PDE10A;LINC00473) SNPs were associated with DH. The SNP heritability of DH was estimated to be 6.7%, with an absence of a genetic correlation with POAG. MR analysis did not reveal a causal association between DH and POAG for East Asian individuals. Conclusions: The novel loci underlying DH in the Korean cohort revealed SNPs in the ELN, CCDC41, and LINC00473 genes. The absence of a causal association between DH and POAG implies that DH is a shared risk factor, rather than an independent culprit factor, and warrants further investigation.

In current software applications, numerous vulnerabilities may be present. Attackers attempt to exploit these vulnerabilities, leading to security breaches, unauthorized entry, data theft, or the incapacitation of computer systems. Instead of addressing software or hardware vulnerabilities at a later stage, it is better to address them immediately or during the development phase. Tools such as AIBugHunter provide solutions designed to tackle software issues by predicting, categorizing, and fixing coding vulnerabilities. Essentially, developers can see where their code is susceptible to attacks and obtain details about the nature and severity of these vulnerabilities. AIBugHunter incorporates VulRepair to detect and repair vulnerabilities. VulRepair currently predicts patches for vulnerable functions at 44%. To be truly effective, this number needs to be increased. This study examines VulRepair to see whether the 44% perfect prediction can be increased. VulRepair is based on T5 and uses both natural language and programming languages during its pretraining phase, along with byte pair encoding. T5 is a text-to-text transfer transformer model with an encoder and decoder as part of its neural network. It outperforms other models such as VRepair and CodeBERT. However, the hyperparameters may not be optimized due to the development of new optimizers. We reviewed a deep neural network (DNN) optimizer developed by Google in 2023. This optimizer, the Evolved Sign Momentum (LION), is available in PyTorch. We applied LION to VulRepair and tested its influence on the hyperparameters. After adjusting the hyperparameters, we obtained a 56% perfect prediction, which exceeds the value of the VulRepair report of 44%. This means that VulRepair can repair more vulnerabilities and avoid more attacks. As far as we know, our approach utilizing an alternative to AdamW, the standard optimizer, has not been previously applied to enhance VulRepair and similar models.

Abstract Background Sarcopenia is characterized by a progressive decrease in skeletal muscle mass and function with age. Given that sarcopenia is associated with various metabolic disorders, effective metabolic biomarkers for its early detection are required. We aimed to investigate the metabolic biomarkers related to sarcopenia in elderly men and perform experimental studies using metabolomics. Methods Plasma metabolites from 142 elderly men, comprising a sarcopenia group and an age‐matched control group, were measured using global metabolome profiling. Muscle and plasma samples from an aging mouse model of sarcopenia, as well as cell media and cell lysates during myoblast differentiation, were analysed based on targeted metabolome profiling. Based on these experimental results, fatty acid amides were quantified from human plasma as well as human muscle tissues. The association of fatty acid amide levels with sarcopenia parameters was evaluated. Results Global metabolome profiling showed that fatty acid amide levels were significantly different in the plasma of elderly men with sarcopenia (all Ps

Background: Monopolar radiofrequency (RF) has emerged as a promising modality for tightening the skin of aged faces. Although many studies have assessed the efficacy of monopolar RF via the clinical evaluation of photographs, few have examined the long-term effectiveness and safety of this therapy using various skin testing devices. Methods: Twenty women with aged faces participated in this study. After a single monopolar RF treatment, three blinded dermatologists who were not involved in the treatment evaluated its clinical efficacy and safety after 4, 12, and 24 weeks. Skin firmness, fine wrinkles, skin pores, and skin tone were also measured using an indentometer (Courage+Khazaka Electronic GmbH, Köln, Germany) and a facial aging measurement device (Mark-Vu; PSI Plus, Suwon-si, Republic of Korea). Results: Skin laxity in the jowls and nasolabial folds showed significant improvement 12 weeks after the single monopolar RF treatment when evaluated by dermatologists, and this improvement lasted 24 weeks (p < 0.05). Moreover, the participants reported improvement at 4 weeks compared to baseline which lasted 24 weeks (p < 0.05). Skin firmness measured in the cheek increased 4 weeks after treatment and continued to improve during 24 weeks of follow-up (p < 0.01). Although there was a gradual increase in improvement in skin pores, fine wrinkles, and skin tones, there were no statistical differences compared to the baseline. No patients experienced pain during the treatment, and no burns, skin breakdown, or scarring occurred after treatment. Conclusions: A single monopolar RF treatment is effective for females with aged face. A significant improvement in the jowls and nasolabial folds and facial skin firmness was observed between the 4- and 24-week follow-ups without adverse effects.

Researchers have proposed a possible correlation between age-related macular degeneration (AMD) and inflammation or C-reactive protein (CRP) levels. We investigated the potential causal relationship between CRP levels and AMD. Single-nucleotide polymorphisms (SNPs) associated with CRP exposure were selected as the instrumental variables (IVs) with significance (p < 5 × 10−8) from the genome-wide association study (GWAS) meta-analysis data of Biobank Japan and the UK Biobank. GWAS data for AMD were obtained from 11 International AMD Genomics Consortium studies. An evaluation of causal estimates, utilizing the inverse-variance-weighted (IVW), weighted-median, MR-Egger, MR-Pleiotropy-Residual-Sum, and Outlier tests, was conducted in a two-sample Mendelian randomization (MR) study. We observed significant causal associations between CRP levels and AMD (odds ratio [OR] = 1.13, 95% CI = [1.02–1.24], and p = 0.014 in IVW; OR = 1.18, 95% CI = [1.00–1.38], and p = 0.044 in weight median; OR = 1.31, 95% CI = [1.13–1.52], and p < 0.001 in MR–Egger). The causal relationship between CRP and AMD warrants further research to address the significance of inflammation as a risk factor for AMD.

Existing literature suggests a controversial relationship between type 2 diabetes mellitus (T2D) and glaucoma. This study aimed to examine the potential causal connection between T2D and glycaemic traits (fasting glucose [FG] and glycated haemoglobin [HbA1c] levels) as exposures to primary open-angle glaucoma (POAG) in multi-ethnic populations. Single-nucleotide polymorphisms associated with exposure to T2D, FG, and HbA1c were selected as instrumental variables with significance (p < 5.0 × 10−8) from the genome-wide association study (GWAS)-based meta-analysis data available from the BioBank Japan and the UK Biobank (UKB). The GWAS for POAG was obtained from the meta-analyses of Genetic Epidemiology Research in Adult Health and Aging and the UKB. A two-sample Mendelian randomisation (MR) study was performed to assess the causal estimates using the inverse-variance weighted (IVW) method, and MR-Pleiotropy Residual Sum and Outlier test (MR–PRESSO). Significant causal associations of T2D (odds ratio [OR] = 1.05, 95% confidence interval [CI] = [1.00–1.10], p = 0.031 in IVW; OR = 1.06, 95% CI = [1.01–1.11], p = 0.017 in MR–PRESSO) and FG levels (OR = 1.19, 95% CI = [1.02–1.38], p = 0.026 in IVW; OR = 1.17, 95% CI = [1.01–1.35], p = 0.041 in MR–PRESSO) with POAG were observed, but not in HbA1c (all p > 0.05). The potential causal relationship between T2D or FG and POAG highlights its role in the prevention of POAG. Further investigation is necessary to authenticate these findings.

Abstract Background The pathogenesis of diabetic kidney disease (DKD) is complex, involving metabolic and hemodynamic factors. Although DKD has been established as a heritable disorder and several genetic studies have been conducted, the identification of unique genetic variants for DKD is limited by its multiplex classification based on the phenotypes of diabetes mellitus (DM) and chronic kidney disease (CKD). Thus, we aimed to identify the genetic variants related to DKD that differentiate it from type 2 DM and CKD. Methods We conducted a large-scale genome-wide association study mega-analysis, combining Korean multi-cohorts using multinomial logistic regression. A total of 33,879 patients were classified into four groups—normal, DM without CKD, CKD without DM, and DKD—and were further analyzed to identify novel single-nucleotide polymorphisms (SNPs) associated with DKD. Additionally, fine-mapping analysis was conducted to investigate whether the variants of interest contribute to a trait. Conditional analyses adjusting for the effect of type 1 DM (T1D)-associated HLA variants were also performed to remove confounding factors of genetic association with T1D. Moreover, analysis of expression quantitative trait loci (eQTL) was performed using the Genotype-Tissue Expression project. Differentially expressed genes (DEGs) were analyzed using the Gene Expression Omnibus database (GSE30529). The significant eQTL DEGs were used to explore the predicted interaction networks using search tools for the retrieval of interacting genes and proteins. Results We identified three novel SNPs [rs3128852 (P = 8.21×10−25), rs117744700 (P = 8.28×10−10), and rs28366355 (P = 2.04×10−8)] associated with DKD. Moreover, the fine-mapping study validated the causal relationship between rs3128852 and DKD. rs3128852 is an eQTL for TRIM27 in whole blood tissues and HLA-A in adipose-subcutaneous tissues. rs28366355 is an eQTL for HLA-group genes present in most tissues. Conclusions We successfully identified SNPs (rs3128852, rs117744700, and rs28366355) associated with DKD and verified the causal association between rs3128852 and DKD. According to the in silico analysis, TRIM27 and HLA-A can define DKD pathophysiology and are associated with immune response and autophagy. However, further research is necessary to understand the mechanism of immunity and autophagy in the pathophysiology of DKD and to prevent and treat DKD.

Objective To investigate the effect of low frequency cerebellar repetitive transcranial magnetic stimulation (rTMS) on balance impairment in patients with cerebral infarction. Methods Thirty-two patients were randomly divided into two groups: rTMS group (n=16) and control (n=16). In the rTMS group, treatment was performed five times per week for 2 weeks (10 sessions), and in the control group, a sham coil was used with the sound and sensation of scalp similar to the rTMS coil. Patients in both groups underwent a conventional rehabilitation program. Berg Balance Scale (BBS) was used as the primary outcome measurement. Timed Up and Go test (TUG), 10-m walk test (10mWT), and Activity-specific Balance Confidence scale (ABC) were used as the secondary outcome measurement. All scales were measured at baseline (T0), after 10 sessions of rTMS (T1), and at 4 weeks after treatment completion (T2) by therapists with over 5 years of clinical experience. Results There were significant improvements between T0 and T1, and between T0 and T2, for all assessed items in the rTMS group. Whereas there were significant improvements between T0 and T1, and between T0 and T2, for the BBS and 10mWT in the control group. TUG (-4.87±5.05 vs. -0.50±2.97 seconds) and ABC score (8.10±8.33 vs. 0.16±0.97) were observed significant differences in comparison of the changes from T0 to T1 between the two group. BBS score (4.40±3.66 vs. 1.88±3.14), TUG (-4.87±4.56 vs. -0.62±2.96 seconds) and ABC score (8.22±7.70 vs. -0.09±0.86) differed significantly from T0 to T2 between the two groups. Conclusion Our findings suggest that low-frequency cerebellar rTMS is helpful for improving balance in patients with cerebral infarction, and maybe a beneficial treatment for these patients.

Objective The Korean Knee Society (KKS) score is used for functional evaluation during follow‐up after total knee arthroplasty (TKA), but it is time‐consuming to measure and is limited by its subjective nature. We investigated whether the global gait asymmetry index (GGA) that can be obtained using the Kinect‐V2 system could overcome the KKS limitations. Methods Forty‐three patients who underwent TKA from January 2019 to December 2019 were included. Postoperatively, regular follow‐up was performed at 2, 4, 6, 8, and 12 weeks, and at 4, 6, and 12 months. At each follow‐up visit, the KKS was measured, and the walking path was followed with six Kinect‐V2 systems. After allowing the participants to walk naturally, the range of motion of each joint of the lower extremity and GGA were obtained. Changes in the KKS and GGA scores and measurement times were investigated until the final follow‐up. A statistical model was made to predict the KKS from the GGA score using data at all observed time points, and analysis of variance (ANOVA) with Turkey's post‐hoc tests and Pearson correlation tests were used for evaluation. Results Both the KKS and GGA scores improved significantly from 4 weeks postoperatively until the final follow‐up. The measurement time was significantly shorter for the GGA (9.3 ± 1.4 min) than for the KKS (32.4 ± 9.2 min; P

Abstract Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with an increased risk of other gynecological disorders, such as endometrial hyperplasia (EH). However, substantial factors in the comorbidity of EH and PCOS remain to be investigated. We analyzed trend changes in PCOS and factors related to the comorbidity of PCOS and EH using data from the Korea National Health Insurance (KNHI) claims database. Methods The data for this population-based study of people diagnosed with PCOS or EH in Korea from 2009 to 2016 were collected from the KNHI claims database between 2007 and 2017. We conducted a trend analysis of the prevalence and incidence of PCOS and EH. In addition, we performed a logistic regression analysis to identify risk factors associated with EH incidence in people with PCOS using the matched case-control methodology. Results The average annual growth rate of the incidence of PCOS was 14.1% from 2009 to 2016, whereas the EH rate increased by only 3.4% annually. Comorbidities, type 2 diabetes, obesity, hypertension, hyperlipidemia, and infertility, increased the risk of EH in PCOS patients. Additionally, the cumulative duration of oral contraceptive & progestin treatment for PCOS correlated highly with the comorbidity of EH and PCOS. Conclusions We confirmed the relationship between PCOS and EH using big data suitable for time series analyses of the diagnosis and treatment of diseases. Endometrial evaluation should be done with more caution if oral contraceptives & progestins have been used for a long time.

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, aberrant differentiation of keratinocytes, and dysregulated immune responses. WW domain-containing oxidoreductase (WWOX) is a non-classical tumor suppressor gene that regulates multiple cellular processes, including proliferation, apoptosis, and migration. This study aimed to explore the possible role of WWOX in the pathogenesis of psoriasis. Immunohistochemical analysis showed that the expression of WWOX was increased in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model. Immortalized human epidermal keratinocytes were transduced with a recombinant adenovirus expressing microRNA specific for WWOX to downregulate its expression. Inflammatory responses were detected using Western blotting, real-time quantitative reverse transcription polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay. In human epidermal keratinocytes, WWOX knockdown reduced nuclear factor-kappa B signaling and levels of proinflammatory cytokines induced by polyinosinic: polycytidylic acid [(poly(I:C)] in vitro. Furthermore, calcium chelator and protein kinase C (PKC) inhibitors significantly reduced poly(I:C)-induced inflammatory reactions. WWOX plays a role in the inflammatory reaction of epidermal keratinocytes by regulating calcium and PKC signaling. Targeting WWOX could be a novel therapeutic approach for psoriasis in the future.

Abstract The nitric oxide pathway plays a critical role in vascular homeostasis. Increased levels of systemic nitric oxide (NO) are observed in preclinical models of sepsis and endotoxemia. This has led to the postulation that vasodilation by inducible nitric oxide synthase (iNOS) generated NO may be a mechanism of hypotension in sepsis. However, contrary to the expected pharmacological action of a nitric oxide synthase (NOS) inhibitor, clinical studies with L-NAME produced adverse cardiac and pulmonary events, and higher mortality in sepsis patients. Thus, the potential adverse effects of NO in human sepsis and shock have not been fully established. In recent years, the emerging new understanding of the NO pathway has shown that an endogenously produced inhibitor of NOS, asymmetric dimethylarginine (ADMA), a host response to infection, may play an important role in the pathophysiology of sepsis as well as organ damage during ischemia–reperfusion. ADMA induces microvascular dysfunction, proinflammatory and prothrombotic state in endothelium, release of inflammatory cytokines, oxidative stress and mitochondrial dysfunction. High levels of ADMA exist in sepsis patients, which may produce adverse effects like those observed with L-NAME. Several studies have demonstrated the association of plasma ADMA levels with mortality in sepsis patients. Preclinical studies in sepsis and ischemia–reperfusion animal models have shown that lowering of ADMA reduced organ damage and improved survival. The clinical finding with L-NAME and the preclinical research on ADMA “bed to bench” suggest that ADMA lowering could be a potential therapeutic approach to attenuate progressive organ damage and mortality in sepsis. Testing of this approach is now feasible by using the pharmacological molecules that specifically lower ADMA.

Objective To investigate the effect of antigravity treadmill gait training (AGT) on gait function, balance, and fall risk in stroke patients. Methods This study included 30 patients with stroke (mean age, 73 years). All subjects were randomly divided into two groups. The intervention group (n=15) performed AGT for 20 minutes, five times per week for 4 weeks. The control group (n=15) received conventional gait training for the same duration. To assess fall risk, the Tinetti Performance-Oriented Mobility Assessment (POMA) was measured. The Berg Balance Scale (BBS), Timed Up and Go test (TUG), and 10-m walk test (10mWT) were measured to assess dynamic balance. All scales were measured before intervention (T0) and at 4 weeks (T1) and 12 weeks (T2) after intervention. Results Results showed that the total POMA score, BBS, and 10mWT scores improved significantly (p

Objectives: Medical facilities have been required to effectively utilize insufficient human resources in many countries. Therefore, we qualitatively and quantitively compared physicians’ working burden, and assessed advantages and disadvantages of the single- and the multiple-attending physicians systems in inpatient care. Methods: In this cross-sectional study, we extracted electronic health record of patients from a hospital in Japan from April 2017 to October 2018 to compare anonymous statistical data between the single-attending and multiple-attending-physicians system. Then, we conducted a questionnaire survey for all physicians of single and multiple-attending systems, asking about their physical and psychiatric workload, and their reasons and comments on their working styles. Results: The average length of hospital stay was significantly shorter in the multiple-attending system than in the single-attending system, while patients’ age, gender, and diagnoses were similar. From the questionnaire survey, no significant difference was found in all categories although physical burden in multiple-attending system tended to be lower than that in single-attending system. Advantages of multiple-attending system extracted from qualitative analysis are (1) improvement of physicians’ quality of life (QOL), (2) lifelong-learning effect, and (3) improving the quality of medical care, while disadvantages were (1) risk of miscommunications, (2) conflicting treatment policies among physicians, and (3) patients’ concern. Conclusions: The multiple-attending physician system in the inpatient setting can reduce the average length of stay for patients and also reduce the physical burden on physicians without compromising their clinical performance.

Abstract Background The microbiome could trigger inflammation leading to epigenetic changes and is involved in the pathophysiology of eye diseases; however, its effect on uveitic glaucoma (UG) has not been fully investigated. This study analysed the differences in eyelid and buccal microbiomes in patients with UG using next-generation sequencing. Methods The eyelid and buccal specimens of 34 UG and 25 control patients were collected. The taxonomic composition of the microbiome was obtained via 16S ribosomal DNA sequencing. Diversity and differential gene expression analyses (DEG) determined taxon differences between the microbiomes of UG and control groups. Results In both the eyelid and buccal microbiomes, alpha-diversity was lower in UG patients than controls, while beta-diversity in patients with UG was higher than in controls. DEG analysis of the eyelid microbiome revealed various taxa differences, including enrichment of Paenibacillus and Dermacoccus (p-value, 1.31e−6 and 1.55e−7, respectively) and depletion of Morganella and Lactococcus (p-value, 6.26e−12 and 2.55e−6, respectively) in patients with UG. In the buccal microbiome, taxa such as Lactococcus was significantly depleted (p-value, 1.31e−17), whereas Faecalibacterium was enriched in patients with UG (p-value, 6.12e−8). Conclusions The eyelid and buccal microbiomes in patients with UG differ from controls, which raises concerns surrounding environmental influences on the pathogenesis of UG. The reduced Lactococcus in the eyelid and buccal area suggest that microbiota dysbiosis is associated with UG.

The Programmed death-1 (PD-1) and its ligand PD-L1 are critical checkpoints in the regulation of immune responses. Here the authors implicate PD-L1 signalling at lymphatic endothelium in the regulation of transendothelial migration of T cells.

Abstract Sarcopenia is an age-related disorder characterised by a progressive decrease in skeletal muscle mass. As the genetic biomarkers for sarcopenia are not yet well characterised, this study aimed to investigate the genetic variations related to sarcopenia in a relatively aged cohort, using genome-wide association study (GWAS) meta-analyses of lean body mass (LBM) in 6961 subjects. Two Korean cohorts were analysed, and subgroup GWAS was conducted for appendicular skeletal muscle mass (ASM) and skeletal muscle index. The effects of significant single nucleotide polymorphisms (SNPs) on gene expression were also investigated using multiple expression quantitative trait loci datasets, differentially expressed gene analysis, and gene ontology analyses. Novel genetic biomarkers were identified for LBM (rs1187118; rs3768582) and ASM (rs6772958). Their related genes, including RPS10, NUDT3, NCF2, SMG7, and ARPC5, were differently expressed in skeletal muscle tissue, while GPD1L was not. Furthermore, the ‘mRNA destabilisation’ biological process was enriched for sarcopenia. Our study identified RPS10, NUDT3, and GPD1L as significant genetic biomarkers for sarcopenia. These genetic loci were related to lipid and energy metabolism, suggesting that genes involved in metabolic dysregulation may lead to the pathogenesis of age-related sarcopenia.

Abstract Background Adequate physical activity (PA) is essential for preventing sarcopenia in older adults. However, there are insufficient epidemiological data on the intensity of PA needed to prevent age-related sarcopenia. The purpose of this study was to investigate the association of PA intensity with skeletal muscle mass and muscle strength. Methods This was a population-based study with a cross-sectional design that was conducted using data from the 2008 − 2011 and 2014 − 2018 Korea National Health and Nutrition Examination Surveys, which included a total of 11,162 participants aged ≥ 60 years. PA was assessed using the results of a questionnaire and organized by intensity, frequency, and duration. The study population was divided into the following groups based on PA intensity: no exercise, walking only, moderate PA, and vigorous PA. To assess sarcopenia, skeletal muscle index (SMI) and hand grip strength (HGS) were measured as indicators of muscle mass and strength, respectively. Logistic regression analysis was used to explore the relationship between PA intensity and sarcopenia. Results SMI and HGS were significantly higher in men and women engaged in moderate to vigorous PA than in those who did not exercise. The odds ratios (ORs) for sarcopenia defined based on SMI and HGS were lowest in men engaged in vigorous PA (0.444, 95% confidence interval [CI]: 0.242 − 0.818 and 0.450, 95% CI: 0.228 − 0.890, respectively). In women, the OR for sarcopenia defined based on HGS was the lowest in the group engaged in vigorous PA (0.441, 95% CI: 0.199 − 0.975), while there was no risk reduction for sarcopenia defined based on SMI. Conclusions Moderate to vigorous PA was highly correlated with SMI and HGS in men and women. Intensive PA was positively correlated with sarcopenia prevention, which can be monitored using HGS.

Researchers have suggested a potential relationship between gamma-glutamyl transferase (GGT) level and stroke. We investigated a potential causal relationship between GGT level as exposures and stroke and stroke subtypes (cardioembolic, small vessel, and large artery) in a European population. We performed a two-sample Mendelian randomization (MR) study using the genome-wide association study (GWAS) data from the UK Biobank as the exposure set. For the outcome set, we used stroke in the GWAS data from the GIGASTROKE Consortium. We considered alcohol consumption, atrial fibrillation, and body mass index as confounders. We used PhenoScanner searches for removal of SNPs and multivariable MR analysis for assessing confounders. We observed significant causal associations between GGT level and stroke (odds ratio [OR] = 1.23, 95% CI = [1.05–1.44], and p = 0.012 with IVW; OR = 1.19, 95% CI= [1.02–1.39], and p = 0.031 with MR-PRESSO). These results were consistent after removing SNPs related to confounding factors. Similarly, in multivariable MR, GGT was associated with stroke after adjusting for confounding factors (OR = 1.30, 95% CI 1.07–1.60), p = 0.010). Because GGT level has a causal relationship with stroke, researchers should test its significance as a potential risk factor for stroke. Additional research is required to validate these results.

Abstract Background A complication associated with the distal locking screw used in the proximal femoral nail (PFN) system is the formation of accidental additional holes. We hypothesized that an increase in stress around additional holes is a relevant factor contributing to fractures. This study aimed to evaluate stress changes in the cortical bone around additional screw holes using finite element analysis. Methods Proximal femoral nail antirotation (PFNA)-II (Synthes, Solothurn, Switzerland) was inserted into a femur model. An additional 4.9-mm transcortical hole was made either anteriorly (anterior hole model) or posteriorly (posterior hole model) to the distal locking screw. Finite element analysis was used to calculate compression, tension, and load limits to investigate stress around additional holes with respect to the direction of screw penetration and degree of osteoporosis. The results were then compared with those of mechanical testing. A 31A-21 type intertrochanteric fracture was applied. As a control group, a model without additional holes (no-hole model) was developed. Repeated load-loading tests were performed on 10 model bones per model group. Results Tensile stress was significantly greater in the no-hole model when additional screw holes were present, and the anterior hole showed a higher maximum stress value than the posterior hole, suggesting that the anterior hole was more susceptible to fracture. The change in tensile stress first appeared in the hole around the lateral cortical bone and proceeded to the medial side. Biomechanical testing showed that fractures around the distal locking screw occurred in 0 cases of the no-hole, 10 of the anterior hole, and 9 of the posterior hole models. Conclusions During PFN surgery for intertrochanteric fracture, holes with distal locking screws fixed and removed at the anterior and posterior of the nail can be a risk factor for fractures in the surrounding area.

Objective. Social media (SM) has gained almost ubiquitous use in society and especially among adolescents; however, there has been rising concern over its negative consequences, including the effects on child behavioral health, such as sleep and internalizing symptoms. Research elucidating the impacts of SM use on young people should be conducted to inform healthier SM usage. This study seeks to understand how SM use and use of phones around bedtime associates with worse sleep quality, depression, and anxiety among youth during the peak of the COVID-19 pandemic and social distancing. Methods. This project uses archival data collected in fall 2020 through school-based surveys to adolescents in a rural school district in Michigan. There were a total of 200 participants (91.7% response rate) of which 180 adolescents (12-15 years old, 40.0% male, 55.6% female, 3.9% nonbinary) were included in the analysis based on their SM use, the majority of whom identified as white (91.7%). Results. Linear regression analyses indicated that higher self-reported SM use was associated with poorer sleep quality and greater depression (p

Background Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS). Methods We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed. Results rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles. Conclusion The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

Abstract Objective When a hip screw needs to be changed, choosing between the conventional (C-type) and helical blade (H-type) types is difficult. In this biomechanical study, we compared these two screw types relative to the type of the initial screw used. Methods C- or H-type screws were inserted (leading screw) in three types of polyurethane bone models (Sawbone, Pacific Research Laboratories, Inc., Washington, USA: 130 × 180 × 40 mm) of different bone mineral densities (pounds per cubic feet [PCF] 5, 80 kg/m3; PCF 10, 160 kg/m3; and PCF 15, 240 kg/m3), and then successively or alternately inserted (following screw) after the leading screw removal. An original model (original C and H) of a leading screw without removal was created as a control. The strengths of resistance to pullout (PO) and rotational stress were measured. For each experimental condition, there were 30 experimental models. Results The original C screw was superior in PO strength, and the original H-type screw was superior in rotational strength. When the C- or H-type screw was the leading screw, using the C-type screw again as the following screw (C1-C2, H1-C2) showed the greatest resistance to PO, and using the H-type screw as the following screw (C1-H2, H1-H2) showed superior resistance to rotational strength. However, the rotational strength of the C2 screw decreased by more than 50% compared with that of the original C screw. Moreover, the PO and rotational strengths of the H2 screw decreased to less than 30% overall compared with those of the original H screw. Conclusion The H-type screw should be used for second-time screw insertion procedures in cases where it is difficult to choose between PO and rotational strengths.

Vitamin D deficiency (VDD) is increasingly prevalent on a global scale and is connected to chronic health issues including diabetes, obesity, and inflammation. This study aimed to investigate the association between VDD and various clinical parameters including glycated hemoglobin (HbA1c), body mass index (BMI), and inflammatory markers. This cross-sectional cohort study included Korean men and women aged 50 years and older (290 men, 125 women); VDD was classified as serum 25-hydroxyvitamin D (25[OH]D) levels below 20 ng/mL. Vitamin D deficiency was more prevalent in men (64.5%) compared to that in women (35.2%). Men with VDD had higher fat mass and HbA1c levels, lower muscle strength, and worse physical performance. Among women, VDD was associated with higher BMI, HbA1c, tumor necrosis factor-alpha (TNF-α), and creatinine levels. In women, 25(OH)D levels exhibited an inverse relationship with HbA1c, BMI, and TNF-α concentrations. However, there were no differences in the levels of interleukin-6 and interleukin-1 beta according to vitamin D status in both men and women. Vitamin D deficiency is linked to higher HbA1c, BMI, and inflammatory markers in older Korean women, thus warranting the maintenance of sufficient vitamin D levels for overall health.

Abstract We report a case of pneumatosis intestinalis (PI) in a hemodialysis patient who presented with anorexia and nausea. Anorexia with postprandial nausea can be caused by gastrointestinal diseases, with one of the rare causes being PI. PI may occur in hemodialysis patients, but it is rarely reported. We experienced a case of benign PI in a hemodialysis patient, for whom the conservative treatment with antibiotics improved the patient's clinical symptoms. In patients with PI, it is important to rule out potentially life‐threatening complications, such as the presence of hepatic intraportal gas on CT scan.

Abstract Findings obtained on objective assessments to evaluate sensitive skin do not correlate well with the symptomatology. We utilized reflectance confocal microscopy (RCM) to compare transepidermal application of zinc in sensitive and non-sensitive skin. Thirty-six subjects participated in this study. They were divided into groups based on lactic acid sting test (LAST):‘stinger’ and ‘non-stinger’; transepidermal water loss (TEWL) measurements; and sensitivity self-assessments: ‘sensitive’ and ‘non-sensitive’. RCM images were taken to visualize transepidermal application of topically-applied zinc. The intensity of zinc reflectance at different depths was measured by ImageJ software. Based on LAST scores, the ‘stinger’ group showed significantly higher reflectance of zinc at 8 µm (stratum corneum) [face (P

Introduction: Despite technical developments in decompression without fusion, many studies still assert that instability could be increased in patients with spinal stenosis and lumbar degenerative spondylolisthesis after spinal decompression surgery without fusion. Thus, this study aimed to describe and assess the clinical outcomes of the semi-circumferential decompression (SCD) technique used for microsurgical en-bloc total ligamentum flavectomy with preservation of the facet joint in treating patients who have lumbar spinal stenosis with two-level degenerative spondylolisthesis. Methods: We retrospectively analyzed the clinical and radiologic outcomes of 14 patients who had spinal stenosis with two-level Meyerding grade I degenerative spondylolisthesis. We evaluated improvements in back pain and radiating pain using a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). We have also examined the occurrence of spinal instability on a radiological exam using slip percentage and slip angle. Results: The mean VAS score of back pain and radiating pain has been determined to decrease significantly from 6.7 to 3.3 and from 8.6 to 2.7, respectively. Meanwhile, the ODI score significantly improved from 27.3 preoperatively to 9.8 postoperatively. Statistically significant change was not observed in the slip percentage in both upper and lower levels. Dynamic slip percentage, which is defined as the difference in the slip percentage between flexion and extension, also did not significantly change. No statistically significant change was found in the slip angle and dynamic slip angle. Conclusions: SCD is a recommendable procedure that can improve clinical results. This procedure does not cause spinal instability when treating patients who have spinal stenosis with two-level degenerative spondylolisthesis.

Objective To compare the convenience and effectiveness of the existing lumbosacral orthoses (LSO) (classic LSO and Cybertech) and a newly developed LSO (V-LSO) by analyzing postoperative data. Methods This prospective cohort study was performed from May 2019 to November 2019 and enrolled and analyzed 88 patients with degenerative lumbar spine disease scheduled for elective lumbar surgery. Three types of LSO that were provided according to the time of patient registration were applied for 6 weeks. Patients were randomized into the classic LSO group (n=31), Cybertech group (n=26), and V-LSO group (n=31). All patients were assessed using the Oswestry Disability Index (ODI) preoperatively and underwent plain lumbar radiography (anteroposterior and lateral views) 10 days postoperatively. Lumbar lordosis (LS angle) and frontal imbalance were measured with and without LSO. At the sixth postoperative week, a follow-up assessment with the ODI and orthosis questionnaire was conducted. Results No significant differences were found among the three groups in terms of the LS angle, frontal imbalance, ODI, and orthosis questionnaire results. When the change in the LS angle and frontal imbalance toward the reference value was defined as a positive change with and without LSO, the rate of positive change was significantly different in the V-LSO group (LS angle: 41.94% vs. 61.54% vs. 83.87%; p=0.003). Conclusion The newly developed LSO showed no difference regarding its effectiveness and compliance when compared with the existing LSO, but it was more effective in correcting lumbar lordosis.

ONC201 was originally discovered as TNF-Related Apoptosis Inducing Ligand (TRAIL)-inducing compound TIC10. ONC201 appears to act as a selective antagonist of the G protein coupled receptor (GPCR) dopamine receptor D2 (DRD2), and as an allosteric agonist of mitochondrial protease caseinolytic protease P (ClpP). Downstream of target engagement, ONC201 activates the ATF4/CHOP-mediated integrated stress response leading to TRAIL/Death Receptor 5 (DR5) activation, inhibits oxidative phosphorylation via c-myc, and inactivates Akt/ERK signaling in tumor cells. This typically results in DR5/TRAIL-mediated apoptosis of tumor cells; however, DR5/TRAIL-independent apoptosis, cell cycle arrest, or antiproliferative effects also occur. The effects of ONC201 extend beyond bulk tumor cells to include cancer stem cells, cancer associated fibroblasts and immune cells within the tumor microenvironment that can contribute to its efficacy. ONC201 is orally administered, crosses the intact blood brain barrier, and is under evaluation in clinical trials in patients with advanced solid tumors and hematological malignancies. ONC201 has single agent clinical activity in tumor types that are enriched for DRD2 and/or ClpP expression including specific subtypes of high-grade glioma, endometrial cancer, prostate cancer, mantle cell lymphoma, and adrenal tumors. Synergy with radiation, chemotherapy, targeted therapy and immune-checkpoint agents has been identified in preclinical models and is being evaluated in clinical trials. Structure-activity relationships based on the core pharmacophore of ONC201, termed the imipridone scaffold, revealed novel potent compounds that are being developed. Imipridones represent a novel approach to therapeutically target previously undruggable GPCRs, ClpP, and innate immune pathways in oncology.

Objectives:In this study, through the results of the high-concentration 2-MIB (2-Methyl Isoborneol) treatment by two different types of advanced treatment plants (Post Peroxone+GAC, UV/H2O2+GAC F/A) which intake raw water from the same water intake facility, the 2-MIB removal characteristics by oxidation process of each WTPs (Water Treatment Plants) were compared and analyzed, and optimal operation methods were derived. Methods:The 2-MIB removal rate was compared and analyzed according to each AOP (Advanced Oxidation Process) operating conditions (Post Peroxone+GAC of the G WTP and UV/H2O2+GAC F/A of the I WTP). The optimal equations of chemical injection were derived through the correlation between the operating conditions of the AOP for each WTPs and 2-MIB removal rate. By analyzing the operating characteristics of each WTPs, the cost and unit price for optimal operation were calculated according to the 2-MIB concentration of raw water and water production. Optimal operating conditions were derived through the performance of oxidation facilities and chemical injection equations of each WTPs, and economical operating plans were reviewed through linked operation of 2 WTPs. Results and Discussion:The 2-MIB removal rates for each WTPs were 70~100% for the G WTP and 50~96% for the I WTP. The operating conditions affecting the 2-MIB removal were [O3 injection×contact time], H2O2/O3 for Post Peroxone of the G WTP, and [UV dose×H2O2 injection] for UV/H2O2 of the I WTP. As a result of comparing the operating cost(electric power cost + chemical cost) of each WTPs, I WTP was 6.6~24.3 KRW/m3 higher than G WTP. It is considered to be because the H2O2 injection was 11~43 times for UV/H2O2 than Post Peroxone. Optimal operating conditions could be derived through the performance evaluation of each oxidation facilities and chemical injection equations of each WTPs. The G WTP and the I WTP are equipped with pipe line for linked operation in the water supply pipes, so the water production for each WTPs can be distributed. In the case of the same water production, it was confirmed that the unit price can be reduced when the water production ratio of the G WTP is increased. Because the decrease in cost of the I WTP is higher than the increase in cost of the G WTP. Conclusions:It was confirmed that both Post Peroxone+GAC of G WTP and UV/H2O2+GAC F/A of I WTP were effective in 2-MIB treatment. As for the operating cost, it was analyzed that UV/H2O2 had higher unit pice than Post Peroxone because of the large amount of H2O2 injection. Considering the 2-MIB removal rate and operating cost of each WTPs, it was possible to derive the optimal operating conditions for each WTPs and a linked operation plan.

Background Parkinson’s disease(PD) affects not only motor symptoms, but also nonmotor symptoms. This study is a clinical trial to determine whether Qigong and acupuncture affect nonmotor symptoms of PD. Methods A 2-arm parallel and randomized trial was performed with 21 participants who had received either Qigong meditation only [control group (CG)] or acupuncture and Qigong meditation [experimental group (EG)]. The participants’ levels of the discomfort in nonmotor symptoms from Parkinson’s disease were evaluated by using the Unified Parkinson’s Disease Rating Scales (UPDRS 1) and Test of Smell Identification (TSI) before and after 12 treatments at baseline and 1 month after 12 treatments. Results The both CG and EG showed improvements in the UPDRS 1 score after treatment by 5.6 ± 5.15 (p= 0.003; 74%) and 4.8 ± 3.80 (p = 0.004; 79%), respectively. The both CG and the EG did improvements in the TSI after treatment by 10.3 ± 4.37 (p < 0.001; 84%) and 12.6 ± 1.77 (p = 0.022; 100%), respectively. However, statistical differences were not observed between the CG and the EG using the UPDRS 1 and the TSI scores. Conclusion The combination of Qigong and acupuncture and Qigong alone was shown to improve the nonmotor symptoms and olfactory function of PD. In the future, large-scale clinical studies on alternative treatment for PD and studies on mechanisms affecting nonmotor symptoms of acupuncture and Qigong are needed.

Background/Aims Recent studies have shown a cumulative dose-dependent association between the use of hydrochlorothiazide (HCTZ) and skin cancer, including melanoma and non-melanoma skin cancer (NMSC) in Western Europe. However, whether this pattern is present in East Asia countries is unknown. The aim of this study was to examine the association between HCTZ use and the risk of skin cancer among a cohort of hypertensive patients in South Korea. Methods This was a retrospective, population-based cohort study using the database from the Health Insurance Review and Assessment Service between January 1, 2007 and June 30, 2017 in South Korea. We identified patients diagnosed with melanoma and NMSC in the cohorts of essential hypertensive patients who were treated with HCTZ or antihypertensive agents other than HCTZ. Using Cox proportional hazards regression models, the hazard ratios (HR) for skin cancer associated with HCTZ users were calculated. Results The risk of melanoma was significantly lower in HCTZ-users compared with non-HCTZ users (HR, 0.85; 95% confidence interval [CI], 0.75 to 0.97; p = 0.016), and the risk of NMSC was lower in the HCTZ users but no statistically significant association was seen (HR, 0.96; 95% CI, 0.91 to 1.02; p = 0.236). High cumulative doses (≥ 50,000 mg) of HCTZ were associated with decreased risk of both NMSC (HR, 0.20; 95% CI, 0.10 to 0.38; p < 0.001) and melanoma (HR, 0.18; 95% CI, 0.04 to 0.70; p = 0.001), respectively. Conclusions High cumulative use of HCTZ may have a chemopreventive effect against the development of melanoma and NMSC with clear cumulative dose-response and duration-response relationships in South Korea.

Purpose: Medical imaging is an indispensable tool in radiotherapy for dose planning, image guidance and treatment monitoring. Cone beam CT (CBCT) is a low dose imaging technique with high spatial resolution capability as a direct by-product of using flat-panel detectors. However, certain issues such as x-ray scatter, beam hardening and other artifacts limit its utility to the verification of patient positioning using image-guided radiotherapy. Methods and Materials: Dual-energy (DE)-CBCT has recently demonstrated promise as an improved tool for tumor visualization in benchtop applications. It has the potential to improve soft-tissue contrast and reduce artifacts caused by beam hardening and metal. In this review, the practical aspects of developing a DE-CBCT based clinical and technical workflow are presented based on existing DE-CBCT literature and concepts adapted from the well-established library of work in DE-CT. Furthermore, the potential applications of DE-CBCT on its future role in radiotherapy are discussed. Results and Conclusions: Based on current literature and an investigation of future applications, there is a clear potential for DE-CBCT technologies to be incorporated into radiotherapy. The applications of DE-CBCT include (but are not limited to): adaptive radiotherapy, brachytherapy, proton therapy, radiomics and theranostics.

Background: Prescription medication sharing is an inappropriate medication use behavior that can lead to medication errors and adverse drug events, posing a public health threat. The reported prevalence of prescription medication lending and borrowing varies by country, ranging from 6%–23% and 5%–52%, respectively. However, research on medication sharing is scant in Asian countries. Therefore, this study aimed to describe the rate of prescription medication sharing practices and investigate the associated behavioral factors, types of shared medications, and reasons for sharing among adults in South Korea.Methods: A cross-sectional study was conducted using an online self-administered survey of 1,000 adults (aged 19–69 years; November 2020). A stratified sampling method was used to select survey participants from a nationwide consumer panel, which ensured a representative distribution of the Korean population by age, gender, and region. Descriptive and logistic regression analyses were used to evaluate the information related to sharing behavior.Results: A total of 1,000 respondents participated in this study. The mean age of the respondents was 44.7 years (standard deviation [SD], 13.4), ranging from 20 to 69 years. The rate of medication sharing was 52.4%. The most prevalently shared medications were analgesic, antipyretic, and antimigraine medications. Prescription medications were shared mostly between family and relatives. Older age was a predictive factor for sharing analgesics. Lower educational level was a predictive factor for sharing ophthalmic medications.Conclusions: Approximately one in two respondents in our study have experienced medication sharing in their lifetime. Future studies are needed to establish evidence-based strategies for patient education and improve the medication use process. Healthcare professionals should assess patients’ needs for accessing medications and be ready to educate and guide them with specific action plans. Policymakers should consider patient empowerment strategies including public education and campaigns to avoid potential adverse outcomes of medication sharing.

Lung cancer is the second most common cancer in the United States, and small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. In SCLC, more than other malignancies, the standard of care is based on clinical demonstration of efficacy, and less on a mechanistic understanding of why certain treatments work better than others. This is in large part due to the virulence of the disease, and lack of clinically or biologically relevant biomarkers beyond routine histopathology. While first line therapies work in the majority of patients with extensive stage disease, development of resistance is nearly universal. Although neuroendocrine features, Rb and p53 mutations are common, the current lack of actionable biomarkers has made it difficult to develop more effective treatments. Some progress has been made with the application of immune checkpoint inhibitors. There are new agents, such as lurbinectedin, that have completed late-phase clinical testing while other agents are still in the pre-clinical phase. ONC201/TIC10 is an imipridone with strong in vivo and in vitro antitumor properties and activity against neuroendocrine tumors in phase 1 clinical testing. ONC201 activates the cellular integrated stress response and induces the TRAIL pro-apoptotic pathway. Combination treatment of lurbinectedin with ONC201 are currently being investigated in preclinical studies that may facilitate translation into clinical trials for SCLC patients.

This exploratory study evaluated the effects of self-regulated strategy development (SRSD) on students' written expression when asked to solve a word problem and explain reasoning. A secondary question evaluated potential for differential effects based on determination of having mathematics difficulty (MD). We implemented a quasi-experimental design with 163 students with and without MD in grade 4. Results indicated that students in the treatment group (n = 83) significantly outperformed students in the comparison group (n = 80) on measures of mathematical writing involving subtraction and division word problems. For the subtraction problems, students in the treatment group improved their overall written expression of mathematics scores (g = 0.688), yielding a medium effect. The intervention differentially benefited students without MD. Our findings call for greater integration of systematic writing opportunities in mathematics and highlight the importance of explicitly teaching students how to approach the written expression of their mathematical reasoning.

Objective: The association between abortion and postmenopausal mental health has not been clearly established in Asian women. The objective of this study was to evaluate the effect of abortion experiences on suicidal ideation and mental health in Korean postmenopausal women. Materials and methods: This study included 5133 postmenopausal women registered in the Korean National Health and Nutrition Examination Survey between 2010 and 2012. Difference in suicidal ideation according to type and number of abortions was analyzed. We used survey multiple logistic regression analysis to evaluate the effect of abortion experiences on the risk for suicidal ideation expressed as adjusted odd ratios (ORs) with 95% confidence intervals (95%CIs). Results: The risk of suicidal ideation was significantly higher in women who experienced more than three abortions (27.9%). While the incidence of suicidal ideation was not significantly affected by the number of spontaneous abortions (p = 0.718), suicidal ideation was significantly more frequent in women who had undergone ≥ three abortions (p = 0.003). After adjusting for demographic confounding factors, women who underwent ≥ three induced abortions had higher risk for suicidal ideation (OR: 1.510; 95% CI: 1.189–1.919; p = 0.031). This risk remained elevated even after controlling for depression (OR: 1.391; 95% CI: 1.1086–1.871, p = 0.002). Moreover, the risk of experiencing a depressive mood in daily life was also increased with increasing number of induced abortions even after controlling for depression (OR: 1.657; 95% CI: 1.274–2.156, p = 0.002). Conclusion: Undergoing three or more induced abortions during reproductive age was associated with postmenopausal suicidal ideation, stress, and depression. However, such association was not noted in those with spontaneous abortion, even in women with more miscarriages. Thus, clinicians should evaluate depression and suicidal ideation in women with multiple induced abortions. Keywords: Abortion, Spontaneous, Menopause, Suicidal ideation

Background/Aims There have been numerous efforts to reduce mother-to-child transmission (MTCT) of hepatitis B virus (HBV) with antiviral agents during pregnancy. However, there are limited data regarding the outcomes of pregnant women after delivery. This study was performed to evaluate the efficacy of antiviral agents in preventing MTCT of HBV and maternal long-term outcomes. Methods The HBV-infected pregnant women treated with antiviral agents to prevent MTCT were retrospectively reviewed. Forty-one pregnant women who received telbivudine or tenofovir during late pregnancy (28-34 week) were analyzed. Hepatitis B virus surface antibody (HBsAb) positivity was tested in 43 infants after 7 months of birth. Eleven mothers were followed >1 year after delivery. Results The mean HBV DNA titer before antiviral therapy was 8.67 (6.60–9.49) log copies/mL, and the median age at delivery was 32 years (range, 22–40). Eleven patients were treated with tenofovir and 30 with telbivudine. The median duration was 57 days (range, 23–100), and the median HBV DNA titer at birth was 5.06 log copies/mL (range, 2.06–6.50). Antiviral treatments were associated with significant HBV DNA reduction (P12 months, and an antiviral agent was administered. Conclusions Antiviral treatment during late pregnancy effectively reduced MTCT. Long-term follow-up should be required in such cases. In addition, given that maternal biochemical flare occurred in 18% of mothers, re-administration of antiviral agents might be required.