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Existing theories of democratic reversals emphasize that elites mount actions like coups when democracy is particularly threatening to their interests. However, existing theory has been largely silent on the role of elite social networks, which interact with economic incentives and may facilitate antidemocratic collective action. We develop a model where coups generate rents for elites and show that the effort an elite puts into a coup is increasing in their network centrality. We empirically explore the model using an original dataset of Haitian elite networks that we linked to firm-level data. We show that central families were more likely to be accused of participating in the 1991 coup against the democratic Aristide government. We then find that the retail prices of staple goods that are imported by such elites differentially increase during subsequent periods of nondemocracy. Our results suggest that elite social structure is an important factor in democratic reversals.

Large numbers of people living under authoritarian governments participate in pro-opposition politics despite sometimes significant risks. Increasing amounts of this political participation are taking place and being organized online. Do emotions play a causal role in inducing pro-opposition participation in authoritarian regimes? Can emotions that mobilize participation be spread via social media? Through an experiment carried out by an opposition party in Zimbabwe, I test whether campaign appeals to opposition supporters’ emotions affect their level of political participation in online pro-opposition discussions. I find that across two different issue areas, randomly assigned anger appeals increase participation on average by 0.4 standard deviations more than enthusiasm appeals with the same informational content. In real terms, this represents between 30% and 170% more participation in the groups assigned to the anger appeals across four different measures of participation. There is little evidence that these effects are stronger in areas with less poverty or that have historically been affected by more violence, or when coupled with messages emphasizing personal power. These results suggest that anger appeals that highlight economic grievances can be an important force for mobilizing online political participation in repressive environments.

Abstract Corneal endothelial cells, situated on the innermost layer of the cornea, are vital for maintaining its clarity and thickness by regulating fluid. In this study, we investigated the differences in the transcriptome between young and old corneal endothelial cells using next-generation sequencing (NGS). Cultured endothelial cells from both young and elderly donors were subjected to NGS to unravel the transcriptomic landscape. Subsequent analyses, facilitated by Metascape, allowed for the dissection of gene expression variances, unearthing pivotal biological pathways. A total of 568 genes showed differences, and were related to Endomembrane system organization, nuclear receptors meta pathway, efferocytosis, etc. Notably, a reduction in the expression of 260 genes was observed in the aged cells form old donors, and in the related analysis, eukaryotic translation initiation, integrator complex, and Hippo YAP signaling were significant. Conversely, 308 genes exhibited elevated expression levels in the elderly, correlating with processes including transition metal ion transport and glycoprotein biosynthesis. In conclusion, our investigation has revealed critical genes involved in the aging process of corneal endothelial cells and elucidated their underlying biological pathways. These insights are instrumental in selecting targets for therapeutic intervention, thereby facilitating the advancement of novel therapeutic approaches for the restoration and preservation of corneal endothelial cell function.

Abstract Regulatory T cells (Tregs) with multifaceted functions suppress anti-tumor immunity by signaling surrounding cells. Here we report Tregs use the surface lymphotoxin (LT)α1β2 to preferentially stimulate LT beta receptor (LTβR) nonclassical NFκB signaling on both tumor cells and lymphatic endothelial cells (LECs) to accelerate tumor growth and metastasis. Selectively targeting LTβR nonclassical NFκB pathway inhibits tumor growth and migration in vitro. Leveraging in vivo Treg LTα1β2 interactions with LTβR on tumor cells and LECs, transfer of wild type but not LTα-/- Tregs promotes B16F10 melanoma growth and tumor cell-derived chemokines in LTβR-/- mice; and increases SOX18 and FLRT2 in lymphatic vessels of LTβR-/- melanoma. Blocking the nonclassical pathway suppresses tumor growth and lymphatic metastasis by reducing chemokine production, restricting Treg recruitment to tumors, and retaining intratumoral IFNγ+ CD8 T cells. Our data reveals that Treg LTα1β2 promotes LTβR nonclassical NFκB signaling in tumor cells and LECs providing a rational strategy to prevent Treg promoted tumor growth and metastasis.

Abstract Poxviruses are implicated in a variety of infectious diseases; however, little is known about the molecular mechanisms that underlie the immune response during poxvirus infection. We investigated the function and mechanisms of the monkeypox virus envelope protein (A30L) and its core peptide (IAMP29) during the activation of innate immune responses. The A30L protein and its core peptide, IAMP29 (a 29-amino-acid inflammasome-activating peptide encompassing His40 to Asp69 of A30L), strongly activated the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome by inducing the production of mitochondrial reactive oxygen species in human monocytes. Specifically, IAMP29 triggered metabolic reprogramming toward glycolysis and interacted with pyruvate kinase M isoforms (PKM1 and PKM2), thus activating the NLRP3 inflammasome and interleukin (IL)-1β production in human monocytes and murine macrophages. In human primary monocyte-derived macrophages, IAMP29-induced inflammasome activation promoted an antimicrobial response to rapidly growing non-tuberculous mycobacteria. Furthermore, IAMP29 exhibited cytotoxic activity against leukemia cells, which was mediated by pyroptosis and apoptosis. These findings provide insights into the immunological function of the poxvirus envelope peptide and suggest its therapeutic potential.

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.

Background/Objectives: Research has suggested a potential relationship between apolipoproteins A (ApoA) and B (ApoB) and age-related macular degeneration (AMD). This study explored the potential causal relationship between ApoA/ApoB levels and AMD/AMD subtypes using two-sample Mendelian randomisation (MR). Methods: We selected 308 single nucleotide polymorphisms (SNPs) for ApoA and 198 SNPs for ApoB from the UK Biobank data. Summary statistics for AMD were collected from the genome-wide association study of the FinnGen project. We performed two-sample MR to assess the causal effects of ApoA/ApoB on AMD and its subtypes. Potential confounders, including body mass index, C-reactive protein level, and smoking status, were assessed using a multivariable MR analysis. Results: ApoA showed a significant causal association with AMD (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.05–1.25, p = 0.003) and was linked to both dry (p = 0.004) and wet (p = 0.025) AMD. ApoB showed a decreasing trend in dry AMD risk (p = 0.074), though not significant, and was not associated with overall or wet AMD. The multivariable MR analysis showed no significant association of ApoA with any AMD subtype (p > 0.05). ApoB decreased dry AMD risk (OR = 0.89, 95% CI = 0.80–0.99, p = 0.039), with trends for overall and wet AMD that were not significant (p = 0.070 and p = 0.091, respectively). Conclusions: These findings suggest that ApoB is associated with lower AMD risk, particularly for dry AMD. Further research is needed to clarify lipid biomarker’s role as AMD risk factors.

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.

Hibernoma is a rare benign tumor of brown adipose tissue. Herein, we report a case of axillary hibernoma in a 53-year-old female and discuss the various radiologic findings. The US revealed a 4.5-cm well-defined oval heterogenous hyperechoic mass in the right axilla with anterior displacement of the axillary vessels. Non-enhanced chest CT showed a 5.0-cm well defined, oval, and low-attenuated mass. MRI demonstrated a 5.5-cm mass with heterogeneous intermediateto-high signal intensity on T1-and T2-weighted images and irregular enhancement at the peripheral portion. The patient underwent an US-guided core needle biopsy and the final diagnosis was hibernoma. [ABSTRACT FROM AUTHOR]

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.

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.

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

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 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 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

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.

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 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.

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

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 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.

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.

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 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.

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.

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

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 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.

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