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Opportunistic fish pathogen Vibrio scophthalmi frequently infects olive flounder and turbot, which are primary marine species cultured for seafood production in Far East Asia. These infections cause substantial yield reductions and significant economic losses. Although quorum sensing (QS) genes were previously reported in V. scophthalmi, the impacts of QS on genome-wide gene expression and consequent behaviors and physiological traits have remained largely unexplored. In this study, we conducted genomic and transcriptomic analyses to uncover the global regulatory network governed by LuxR Vs , a QS master regulator in V. scophthalmi. By comparing the wild-type strain and a luxR Vs deletion mutant strain, we found that LuxR Vs positively regulates biosynthetic genes for poly-hydroxyalkanoate (PHA) while negatively controlling genes for biofilm formation. Quantification of intracellular PHAs and biofilm biomass on borosilicate tubes confirmed these results. Gene set enrichment analyses further demonstrated that LuxR Vs also governs genes related to osmoprotection and defense against reactive oxygen species. Overall, these findings indicate that LuxR Vs acts as a global transcriptional regulator, controlling a wide range of physiological processes in V. scophthalmi. Targeting LuxR Vs could therefore be a promising strategy for improving seafood production by disrupting diverse physiological and pathogenic traits in this fish pathogen., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Metabolic syndrome is a significant risk factor for poor graft outcomes in kidney transplant (KT) patients. However, the effects of variability in metabolic parameters on graft outcomes in KT patients have not been completely elucidated. A total of 852 KT patients were included from the Korean Organ Transplantation Registry. The study exposure was variability in body mass index (BMI) or other metabolic parameters measured at 6 months, 1 year, and 2 years after KT. Patients were classified into tertiles according to the degree of variability. The primary outcome was a composite of adverse kidney outcomes, such as death-censored graft loss or ≥ 30% decline in estimated glomerular filtration rate. The adverse kidney outcomes occurred in 73 (8.6%) participants. The high-BMI variability group had a higher risk for adverse kidney outcomes compared to the low-variability group. High variabilities in triglyceride, fasting blood glucose, and systolic blood pressure were also associated with adverse kidney outcomes. Furthermore, high variability in metabolic syndrome-related composite indices, such as the triglyceride and glucose index and metabolic variability scores, showed a higher risk for adverse kidney outcomes. In conclusion, high variability in metabolic parameters could be associated with an increased risk of adverse kidney outcome in KT patients., (© 2024. The Author(s).)

This paper presents experimental results of combined cyclic load testing on a reinforced concrete (RC) column that was retrofitted with newly designed steel rods. The steel rods were installed around the column longitudinally and then anchored. The proposed steel rods utilize simple components and installation to enhance both the strength and ductility of RC columns. Cyclic lateral load tests were conducted on three specimens: one unreinforced specimen as reference, one specimen with the entire length of the column retrofitted, and one specimen with only the plastic hinge region of the column retrofitted. All specimens were tested under eccentric constant axial load and incrementally increasing lateral loading cycles with eccentricity. The implementation of steel rods resulted in significant improvement in ductility and an up to 60% increase in ultimate loading capacity., (© 2024. The Author(s).)

Glioblastoma (GBM) is a highly aggressive and deadly brain cancer. Temozolomide (TMZ) is the standard chemotherapeutic agent for GBM, but the majority of patients experience recurrence and invasion of tumor cells. We investigated whether TMZ treatment of GBM cells regulates matrix metalloproteinases (MMPs), which have the main function to promote tumor cell invasion. TMZ effectively killed GL261, U343, and U87MG cells at a concentration of 500 µM, and surviving cells upregulated MMP9 expression and its activity but not those of MMP2. TMZ also elevated levels of MMP9 mRNA and MMP9 promoter activity. Subcutaneous graft tumors survived from TMZ treatment also exhibited increased expression of MMP9 and enhanced gelatinolytic activity. TMZ-mediated MMP9 upregulation was specifically mediated through the phosphorylation of p38 and JNK. This then stimulates AP-1 activity through the upregulation of c-Fos and c-Jun. Inhibition of the p38, JNK, or both pathways counteracted the TMZ-induced upregulation of MMP9 and AP-1. This study proposes a potential adverse effect of TMZ treatment for GBM: upregulation of MMP9 expression potentially associated with increased invasion and poor prognosis. This study also provides valuable insights into the molecular mechanisms by which TMZ treatment leads to increased MMP9 expression in GBM cells., (© 2024. The Author(s).)

Human space exploration poses inherent risks to astronauts' health, leading to molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these changes bear similarities to those observed during the aging process on Earth. However, our understanding of the connection between these molecular shifts and disease development in space remains limited. Frailty syndrome, a clinical syndrome associated with biological aging, has not been comprehensively investigated during spaceflight. To bridge this knowledge gap, we leveraged murine data obtained from NASA's GeneLab, along with astronaut data gathered from the JAXA and Inspiration4 missions. Our objective was to assess the presence of biological markers and pathways related to frailty, aging, and sarcopenia within the spaceflight context. Through our analysis, we identified notable changes in gene expression patterns that may be indicative of the development of a frailty-like condition during space missions. These findings suggest that the parallels between spaceflight and the aging process may extend to encompass frailty as well. Consequently, further investigations exploring the utility of a frailty index in monitoring astronaut health appear to be warranted., (© 2024. The Author(s).)

Previous studies have examined the prevalence of allergic diseases in adolescents 1-2 years after the emergence of the COVID-19 pandemic. However, more data is needed to understand the long-term impact of COVID-19 on allergic diseases. Thus, we aimed to examine the trend of the atopic dermatitis prevalence in Korean adolescents before and during the COVID-19 pandemic across 14 years. Additionally, we analyze the risk factors of atopic dermatitis (AD) based on the results. The Korean Disease Control and Prevention Agency conducted the Korea Youth Risk Behavior Web-based Survey from 2009 to 2022, from which the data for this study were obtained. Prevalence trends were compared across subgroups, and the β difference (β diff ) was calculated. We computed odds ratios to examine changes in the disease prevalence before and during the pandemic. This study included a total of 917,461 participants from 2009 to 2022. The prevalence of atopic dermatitis increased from 6.79% (95% CI 6.66-6.91) in 2009-2011 to 6.89% (95% CI 6.72-7.05) in 2018-2019, then decreased slightly to 5.82% (95% CI 5.60-6.04) in 2022. Across the 14 years, middle school student status, low parent's highest education level, low household income, non-alcohol consumption, non-smoker smoking status, no suicidal thoughts, and no suicide attempts were associated with increased risk of atopic dermatitis, while female sex, rural residence, high BMI, low school performance, low household income, and no feelings of sadness and despair was associated with a small increase. This study examined the prevalence of atopic dermatitis across an 18-year, and found that the prevalence increased in the pre-pandemic then decreased during the start of the pandemic and remained constant throughout the pandemic. This trend could be explained mainly by the large scale social and political changes that occurred during the COVID-19 pandemic., (© 2024. The Author(s).)

Prior research has predominantly focused on the overall effects of the tobacco tax increase and the COVID-19 pandemic on adolescent smoking behavior. However, there is a need to examine both the immediate and sustained associations of these two factors on subgroups of adolescents, employing an interrupted time-series model. We aimed to investigate the immediate and sustained association of tobacco tax increase and the COVID-19 pandemic on adolescent smoking prevalence. This study utilized data from the Korea Youth Risk Behavior Web-Based Survey to analyze the prevalence of current smoking among all participants (CSP) and the prevalence of daily smoking among current smokers (DSP) of Korean adolescents (n = 1,159,995; mean, age 14.99; male 51.5%) over 18 years from 2005 to 2022. The study examined 18-year trends in CSP and DSP among Korean adolescents, emphasizing the influences of the 2015 tobacco tax increase and the COVID-19 pandemic, using β coefficients and their differences (β diff ) from an interrupted time-series ARIMA model. While CSP exhibited a decreasing trend, DSP exhibited an increasing trend. Tobacco tax increase was associated with both the short and long terms in smoking prevalence, however, the short-term association on prevalence (CSP, - 3.076 [95% CI, - 3.707 to - 2.445]; DSP, - 4.112 [95% CI, - 6.488 to - 1.735]) was stronger. The pandemic was associated with an immediate increase in DSP (9.345 [95% CI, 5.285-13.406]). These effects were strongest among adolescents from low economic status and those exposed to familial secondhand smoking. Supportive programs for adolescents in low-income families will help overcome the effects associated with the pandemic. As a tobacco tax increase was associated with a reduction in smoking prevalence, this could be one method to overcome the effects of the pandemic., (© 2024. The Author(s).)

This study investigated the impact of target template variation or consistency on attentional bias in location probability learning. Participants conducted a visual search task to find a heterogeneous shape among a homogeneous set of distractors. The target and distractor shapes were either fixed throughout the experiment (target-consistent group) or unpredictably varied on each trial (target-variant group). The target was often presented in one possible search region, unbeknownst to the participants. When the target template was consistent throughout the biased visual search, spatial attention was persistently biased toward the frequent target location. However, when the target template was inconsistent and varied during the biased search, the spatial bias was attenuated so that attention was less prioritized to a frequent target location. The results suggest that the alternative use of target templates may interfere with the emergence of a persistent spatial bias. The regularity-based spatial bias depends on the number of attentional shifts to the frequent target location, but also on search-relevant contexts., (© 2024. The Author(s).)

In this multi-center, assessor-blinded pilot study, the diagnostic efficacy of cCeLL-Ex vivo, a second-generation confocal laser endomicroscopy (CLE), was compared against the gold standard frozen section analysis for intraoperative brain tumor diagnosis. The study was conducted across three tertiary medical institutions in the Republic of Korea. Biopsy samples from newly diagnosed brain tumor patients were categorized based on location and divided for permanent section analysis, frozen section analysis, and cCeLL-Ex vivo imaging. Of the 74 samples from 55 patients, the majority were from the tumor core (74.3%). cCeLL-Ex vivo exhibited a relatively higher diagnostic accuracy (89.2%) than frozen section analysis (86.5%), with both methods showing a sensitivity of 92.2%. cCeLL-Ex vivo also demonstrated higher specificity (70% vs. 50%), positive predictive value (PPV) (95.2% vs. 92.2%), and negative predictive value (NPV) (58.3% vs. 50%). Furthermore, the time from sample preparation to diagnosis was notably shorter with cCeLL-Ex vivo (13 min 17 s) compared to frozen section analysis (28 min 28 s) (p-value < 0.005). These findings underscore cCeLL-Ex vivo's potential as a supplementary tool for intraoperative brain tumor diagnosis, with future studies anticipated to further validate its clinical utility., (© 2024. The Author(s).)

To compare the efficacy of scleral buckling with adjuvant pneumatic retinopexy (SB with PR) and scleral buckling (SB) alone for primary rhegmatogenous retinal detachment (RRD). This retrospective and comparative study included patients who underwent SB with PR (n = 88) or SB alone (n = 161) for primary RRD. The primary anatomical success rate for SB with PR was 81.8%, whereas that for SB alone was 80.7% (P = 0.836). Among patients who achieved primary anatomical success, those in the SB with PR group showed postoperative epiretinal membrane (ERM) formation more frequently than those in the SB alone group (11 of 72 [15.3%] vs. 6 of 130 [4.6%]) (P = 0.009). The mean time to subretinal fluid absorption was not significantly different between the SB with PR and SB alone groups (11.2 ± 6.2 vs. 11.4 ± 5.8 months, P = 0.881). In the SB with PR group, retinal detachment involving ≥ three quadrants was a significant risk factor for surgical failure (hazard ratio, 3.04; P = 0.041). Adjuvant pneumatic retinopexy does not provide additional benefit in improving the surgical outcomes of SB for primary RRD repair., (© 2024. The Author(s).)

Inflammation is implicated as a cause in many diseases. Most of the anti-inflammatory agents in use are synthetic and there is an unmet need for natural substance-derived anti-inflammatory agents with minimal side effects. Aiouea padiformis belongs to the Lauraceae family and is primarily found in tropical regions. While some members of the Aiouea genus are known to possess anti-inflammatory properties, the anti-inflammatory properties of Aiouea padiformis extract (AP) have not been investigated. In this study, we aimed to examine the anti-inflammatory function of AP through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and elucidate the underlying mechanisms. Treatment with AP inhibited the secretion of interleukin-1 beta (IL-1β) mediated by NLRP3 inflammasome in J774A.1 and THP-1 cells without affecting the viability. In addition, AP treatment did not influence NF-κB signaling, potassium efflux, or intracellular reactive oxygen species (ROS) production-all of which are associated with NLRP3 inflammasome activation. However, intriguingly, AP treatment significantly reduced the ATPase activity of NLRP3, leading to the inhibition of ASC oligomerization and speck formation. Consistent with cellular experiments, the anti-inflammatory property of AP in vivo was also evaluated using an LPS-induced inflammation model in zebrafish, demonstrating that AP hinders NLRP3 inflammasome activation., (© 2024. The Author(s).)

Although food labeling on food packages is crucial for promoting a healthy diet, limited research has been conducted on how the COVID-19 pandemic (hereinafter "the pandemic") has affected food labeling awareness. Therefore, this study aims to analyze the changes in trends in food labeling awareness, comprehension, and usage in South Korea during the pandemic. We utilized a nationwide, large-scale, and long-term dataset provided by the Korea Community Health Survey (KCHS) from 2014 to 2022 (total = 1,756,847 participants). This allowed the researchers to assess the long-term trends in the prevalence of food labeling awareness, comprehension, and usage. Furthermore, we investigated the factors associated with awareness specifically related to the pandemic. In total, 1,756,847 adults (54.19% women) participated in this study. The upward slope in overall food labeling awareness became less pronounced and even exhibited a downward slope during the pandemic (βdiff - 1.759; 95% CI - 1.874 to - 1.644). The upward slope in food labeling comprehension and usage became more pronounced during the pandemic (comprehension: βdiff 0.535; 95% CI 0.436-0.634; usage: βdiff 0.693; 95% CI 0.601-0.785). The vulnerability factors associated with lower food labeling awareness during the pandemic included older age, male, obesity, residing in rural areas, lower household income, lower educational level, smoking, and increased alcohol consumption. This study analyzed the 9-year trend in the prevalence of food labeling awareness, comprehension, and usage based on nationally representative data of adults in South Korea from 2014 to 2022. Our findings suggest that personalized nutrition strategies are needed to recognize vulnerable groups with risk factors and improve food labeling awareness among Korean adults during the pandemic., (© 2024. The Author(s).)

Cardiovascular disease remains a leading cause of morbidity and mortality after kidney transplantation (KT). Although statins reduce cardiovascular risk and have renal benefits in the general population, their effects on KT recipients are not well-established. We studied the effects of early statin use (within 1-year post-transplantation) on long-term outcomes in 714 KT recipients from the Korean cohort study for outcome in patients with KT. Compared with the control group, statin group recipients were significantly older, had a higher body mass index, and had a higher prevalence of diabetes mellitus. During a median follow-up of 85 months, 74 graft losses occurred (54 death-censored graft losses and 20 deaths). Early statin use was independently associated with lower mortality (hazard ratio, 0.280; 95% confidence interval 0.111-0.703) and lower death-censored graft loss (hazard ratio, 0.350; 95% confidence interval 0.198-0.616). Statin therapy significantly reduced low-density lipoprotein cholesterol levels but did not decrease the risk of major adverse cardiovascular events. Biopsy-proven rejection and graft renal function were not significantly different between statin and control groups. Our findings suggest that early statin use is an effective strategy for reducing low-density lipoprotein cholesterol and improving patient and graft survival after KT., (© 2024. The Author(s).)

Death with a functioning graft is important cause of graft loss after kidney transplantation. However, little is known about factors predicting death with a functioning graft among kidney transplant recipients. In this study, we evaluated the association between post-transplant creatinine-cystatin C ratio and death with a functioning graft in 1592 kidney transplant recipients. We divided the patients into tertiles based on sex-specific creatinine-cystatin C ratio. Among the 1592 recipients, 39.5% were female, and 86.1% underwent living-donor kidney transplantation. The cut-off value for the lowest creatinine-cystatin C ratio tertile was 0.86 in males and 0.73 in females. The lowest tertile had a significantly lower 5-year patient survival rate and was independently associated with death with a functioning graft (adjusted hazard ratio 2.574, 95% confidence interval 1.339-4.950, P < 0.001). Infection was the most common cause of death in the lowest tertile group, accounting for 62% of deaths. A low creatinine-cystatin C ratio was significantly associated with an increased risk of death with a functioning graft after kidney transplantation., (© 2024. The Author(s).)

A wind-driven triboelectric nanogenerator (W-TENG) is a promising energy harvesting device due to its clean, ubiquitous and unexhausted properties. In addition, a W-TENG induces unpredictable chaotic outputs from wind flow that can serve as an entropy source for cryptography. This can be applied to a true random number generator (TRNG) for a secured system due to its inherent turbulent nature; thus, a W-TENG with a two-in-one structure can simultaneously generate both power and true random numbers. However, a previously reported W-TENG had one major drawback: a wind velocity of 10 m/s is required for stable energy harvesting by wind force. Thus, it is timely to demonstrate a W-TENG-based RNG whose operating condition is below 3 m/s, which is a gentle breeze similar to natural wind. In this study, we demonstrate a wind-driven cryptographic triboelectric random number generator (WCT-RNG) by using a W-TENG whose operating condition for wind speed is below 3 m/s by adopting a rear-fixed film structure instead of a conventional structure. The rear-fixed film refers to the fluttering film being freestanding on the front-side and fixed on the rear-side, where the front- and rear-sides are the wind inlet and outlet, respectively. The WCT-RNG enables the W-TENG to operate below a 3 m/s wind velocity. Because of this, the working time of the WCT-RNG is dramatically enhanced from only 8-42% at an average altitude above sea level. As the capability of operating at low wind speeds is significantly improved, a WCT-RNG becomes more useful and practical for generating both power and true random numbers in a single device. The device can thereby lead to the construction of a self-powered TRNG and secure communication for Internet of Things (IoT) devices in various environments, even under a gentle breeze. In this study, we explain the design of a WCT-RNG structure and also evaluate its randomness by using an NIST SP 800-22 B test suite with a reliability test., (© 2024. The Author(s).)

To investigate the relationship between polycystic ovary syndrome (PCOS) and risk of cardiocerebrovascular disease in Korean women. This longitudinal cohort study using data from the Korean National Health Insurance Service included the women aged 15-44 years diagnosed with PCOS between 2002 and 2019, and the controls were matched 1:3 by age group, income, and region of residence. The endpoint outcomes of this study were the occurrence of ischemic heart disease, cerebrovascular diseases, and combined cardiocerebrovascular diseases in the PCOS and control groups. A stratified Cox proportional hazards regression analysis for matched data was performed to evaluate the relative hazard of events in the PCOS group compared to that in the control group. Among a total of 549,400 participants in the cohort, 137,416 women had a diagnosis of PCOS and 412,118 women did not have it. During a median follow-up of 54 months (interquartile range, 30-78 months), the incidence rates of all cardiovascular, ischemic heart, and cerebrovascular diseases were 6.6, 4.0, and 2.9, respectively, per 1000 person-years for women with PCOS, and 4.8, 2.8, and 2.3, respectively, per 1000 person-years for healthy control women. Women with PCOS had a higher hazard ratio of 1.224 (95% confidence interval, 1.18-1.27) of the composite cardiocerebrovascular diseases than those in the controls after propensity score matching for confounding variables, including body mass index, diabetes mellitus, hypertension, dyslipidemia, physical exercise level, alcohol consumption, current smoking, systolic and diastolic blood pressures, total cholesterol, and triglyceride levels. Hazard ratio for ischemic heart and cerebrovascular diseases was higher in women with PCOS than in the control group (hazard ratio, 1.254; 95% confidence interval, 1.20-1.31 and hazard ratio, 1.201; 95% confidence interval, 1.14-1.27, respectively). PCOS is associated with an increased risk of cardiocerebrovascular diseases in Korean women irrespective of their obesity. Counselling on the management of long-term risk of cardiovascular diseases should be offered to women with PCOS in East Asian countries where PCOS is characterized by a relatively low BMI., (© 2024. The Author(s).)

The correlation between tonsil microbiome and tonsillar hypertrophy has not been well established. Given that oral dysbiosis is related to several metabolic diseases and that tonsillar hypertrophy leads to disordered breathing during sleep and obesity in children, it is necessary to investigate the relationship between the oral microbiome and tonsillar hypertrophy. After 16S rRNA amplicon sequencing of tonsillectomy samples, we evaluated the correlation between the tonsil microbiome and biochemical blood indices in pediatric patients who underwent tonsillectomy. Groups are classified into two categories: based on BMI, and grades 2, 3, and 4 based on tonsil size. Children with obesity and tonsillar hypertrophy have similar microbiome compositions and induce comparable changes in microbiome abundance and composition, confirming the association from a metagenomic perspective. In addition, obesity and tonsillar hypertrophy demonstrated a strong correlation with the Proteobacteria to Firmicutes (P/F) ratio, and among various biochemical indicators, alanine aminotransferase (ALT) levels increase with obesity and tonsillar hypertrophy, indicating a possible association of tonsil microbiome and liver metabolism. These novel findings demonstrate the significance of the tonsil microbiome and suggest the need for tonsil regulation, particularly during childhood., (© 2023. The Author(s).)

The impact of the pandemic on hypertension management is unknown, particularly regarding changes in demographic risk factors. We conducted a comprehensive study between 1998 and 2021 on the long-term trends in hypertension prevalence in South Korea, including a comparison of the pre-pandemic and pandemic eras. Data from 1998 to 2021 of 108,687 Korean adults were obtained through a nationwide, large-scale, and serial study. We conducted a weighted complex sampling analysis on the estimates of national prevalence and compared the slope of hypertension prevalence before and during the pandemic to determine the trend dynamics. We included 108,687 participants over 24 years, 1998-2021. While the prevalence of patients with hypertension consistently increased before the pandemic from 25.51% [95% CI: 24.27-26.75] in 1998-2005 to 27.81% [95% CI: 26.97-28.66] in 2016-2019, the increasing slope in hypertension prevalence slowed during the pandemic period (28.07% [95% CI: 26.16-29.98] for 2021; β diff , -0.012 [-0.023 to 0.000]). Hypertension awareness, treatment, control, and control rates among patients receiving treatment followed similar trends. Compared to the pre-pandemic era, individuals aged 19-59 years or male had significantly increased control rates among the treated patients during the pandemic. This study investigated long-term trends in hypertension prevalence, awareness, treatment, and control among Korean adults. The absence of a reduction in the health indicators associated with hypertension during the pandemic implies that medical services for individuals with hypertension remain unaffected., (© 2023. The Author(s).)

Orthopaedic surgeons need to correctly identify bone fragments using 2D/3D CT images before trauma surgery. Advances in deep learning technology provide good insights into trauma surgery over manual diagnosis. This study demonstrates the application of the DeepLab v3+ -based deep learning model for the automatic segmentation of fragments of the fractured tibia and fibula from CT images and the results of the evaluation of the performance of the automatic segmentation. The deep learning model, which was trained using over 11 million images, showed good performance with a global accuracy of 98.92%, a weighted intersection over the union of 0.9841, and a mean boundary F1 score of 0.8921. Moreover, deep learning performed 5-8 times faster than the experts' recognition performed manually, which is comparatively inefficient, with almost the same significance. This study will play an important role in preoperative surgical planning for trauma surgery with convenience and speed., (© 2023. The Author(s).)

The clinical effects of tacrolimus (TAC) exposure on hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) remain unclear. In this retrospective single centric study, 512 patients who underwent LT for HCC were divided into four groups according to cumulative exposure to tacrolimus (CET) during 3 months after LT: conventional (n = 218), aggressive minimization (n = 32), minimization (n = 161), and high exposure (n = 101). Impact of CET on HCC recurrence and death were analyzed. Compared with the conventional group, the other three CET groups showed a similar risk of HCC recurrence. The aggressive minimization group showed a higher risk [hazard ratio (HR) 5.64, P < 0.001] and the high exposure group showed a marginal risk (HR 1.67, P = 0.081) of overall death compared to the conventional group. CET during 3 months was not associated with HCC recurrence in the matched cohort and various subgroups. TAC minimization is not effective to prevent HCC recurrence but could result in higher mortality in LT recipients., (© 2023. The Author(s).)

The dosage-dependent recruitment of RNA polymerase II (Pol II) at the promoters of genes related to neurodevelopment and stem cell maintenance is required for transcription by the fine-tuned expression of SET-domain-containing protein 5 (SETD5). Pol II O-GlcNAcylation by O-GlcNAc transferase (OGT) is critical for preinitiation complex formation and transcription cycling. SETD5 dysregulation has been linked to stem cell-like properties in some cancer types; however, the role of SETD5 in cancer cell stemness has not yet been determined. We here show that aberrant SETD5 overexpression induces stemness in colorectal cancer (CRC) cells. SETD5 overexpression causes the upregulation of PI3K-AKT pathway-related genes and cancer stem cell (CSC) markers such as CD133, Kruppel-like factor 4 (KLF4), and estrogen-related receptor beta (ESRRB), leading to the gain of stem cell-like phenotypes. Our findings also revealed a functional relationship between SETD5, OGT, and Pol II. OGT-catalyzed Pol II glycosylation depends on SETD5, and the SETD5-Pol II interaction weakens in OGT-depleted cells, suggesting a SETD5-OGT-Pol II interdependence. SETD5 deficiency reduces Pol II occupancy at PI3K-AKT pathway-related genes and CD133 promoters, suggesting a role for SETD5-mediated Pol II recruitment in gene regulation. Moreover, the SETD5 depletion nullified the SETD5-induced stemness of CRC cells and Pol II O-GlcNAcylation. These findings support the hypothesis that SETD5 mediates OGT-catalyzed O-GlcNAcylation of RNA Pol II, which is involved in cancer cell stemness gain via CSC marker gene upregulation., (© 2023. The Author(s).)

Studies on the trends in the prevalence of rheumatoid arthritis (RA) and osteoarthritis (OA) are limited, particularly during the COVID-19 pandemic. This study aimed to analyze the temporal trend of RA and OA in South Korean adults from 1998 to 2021, including the COVID-19 pandemic period. The Korea National Health and Nutrition Examination Survey (KNHANES) data on adults aged ≥ 19 years were analyzed to investigate the prevalence of RA and OA from 1998 to 2021. The prevalence trends were compared by the years, and β diff (β difference) was calculated. Odds ratios (ORs) were computed for each disease to examine changes in disease prevalence before and during the pandemic in order to determine the impact of the pandemic on disease prevalence. Among 163,221 Korean adults, the prevalence of RA and OA showed a steady decrease from 2005 (RA: from 1.91% in 2005-2007 to 1.55% in 2016-2019 and OA: from 9.75% in 2005-2007 to 8.27% in 2016-2019), but there was a slight increased after the onset of the COVID-19 pandemic (RA: from 1.23% in 2020 to 1.36% in 2021 and OA: from 8.04% in 2020 to 8.27% in 2021). Vulnerable groups, including participants aged ≥ 60 years (versus 19-60 years, ratio of ORs: 1.222; 95% CI 1.011-1.477), urban residents (ratio of ORs: 1.289; 95% CI 1.007-1.650), and participants with higher education level (ratio of ORs: 1.360; 95% CI 1.119-1.653) showed higher ORs of OA, whereas no particularly vulnerable population was observed for RA. Our findings provide an insight into the long-term trends of RA and OA among adult population and highlight a novel perspective on the impact of COVID-19 on disease prevalence., (© 2023. The Author(s).)

Disproportionate impact of COVID-19 on socioeconomic and behavioral variables may have impacted the prevalence of diabetes. We utilized nationwide long-term serial study from the 2009 to 2021 Korea Community Health Survey (KCHS). We explored national and regional prevalence and trends of diabetes according to the socioeconomic and behavioral factors before and during the pandemic. Also, we interpreted which groups became more vulnerable to the prevalence of diagnosed diabetes during the pandemic. A total of 2,971,349 adults aged (19 to 39, 40 to 59, and ≥ 60 years) were included in the analysis. The prevalence of diagnosed diabetes increased slowly during the pandemic (11.6% [95% CI 11.5-11.7] in 2020 and 12.4% [95% CI 12.3-12.6] in 2021), compared to the pre-pandemic era (7.9% [95% CI 7.8-7.9] in 2009-2011 and 11.3% [95% CI 11.3-11.4] in 2018-2019). Also, women, low-income group, low-educational group, and infrequent walking group showed less prevalence of diagnosed diabetes than the others. The diabetic population increased slowly than expected during the pandemic. The pandemic seems to contribute to an unanticipated increase in under-diagnosis of diabetes among the already minority. This study may suggest reinforcing access to healthcare services among the minority during the pandemic., (© 2023. Springer Nature Limited.)

Wind-driven triboelectric nanogenerators (W-TENGs) are a promising candidate for an energy harvester because wind itself possesses unexhausted, ubiquitous, and clean properties. W-TENG has also been used as a random number generator (RNG) due to the inherent chaotic properties of wind that is also an entropy source. Thus, a W-TENG which simultaneously generates both power and true random numbers with a two-in-one structure, is a wind-driven RNG (W-RNG) like the Janus. However, a root cause of W-RNG unpredictability has not been elucidated. In this work, the unpredictability, which is essential and critical for an RNG, is statistically and mathematically analyzed by auto-correlation, cross-correlation, joint entropy, and mutual information. Even though the overall shape of the total output analog signals from the W-RNG looks like a sinusoidal wave that is not obviously unpredictable, discretized digital signals from the continuous analog output become unpredictable. Furthermore, partial adoption of 4-bit data from 8-bit raw data, with the aid of analog-to-digital converter hardware, further boosts the unpredictability. The W-RNG, which functions as a W-TENG, can contribute to self-powering and self-securing outdoor electrical systems, such as drones, by harvesting energy and generating true random numbers., (© 2023. Springer Nature Limited.)

The widespread use of body weight control agents might be related to liver enzyme elevation, but this potential association has only been documented in a few case reports. This study aimed to investigate the associations between weight loss agents and elevated liver enzymes at the population-level. We conducted a cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES) data from 2013 to 2019. This study included 36,259 participants over 20 years of age who completed the questionnaire and had no history of hepatitis, cancer, or renal failure. In these participants, we analyzed associations between weight loss agents and elevated liver enzymes by constructing multiple logistic regression models with adjustment for confounding factors and stratified by sex, age, and body mass index. The use of weight loss agents related to liver enzyme elevation in men (adjusted odds ratio (aOR): 1.36, 95% confidence interval (CI): 1.08-1.71) and participants aged less than 40 years (aOR: 1.44, 95% CI: 1.12-1.87). Using more types of weight loss agents was associated with liver enzyme elevation (aOR: 1.31, 95% CI: 1.03-1.67 for 1 weight loss agent, aOR: 1.93, 95% CI: 0.93-3.99 for ≥ 2 weight loss agents). Elevated liver enzymes were associated with the use of traditional medicines (aOR: 1.96, 95% CI: 1.14-3.34) and dietary supplements (aOR: 1.33, 95% CI: 1.02-1.72) in men. We observed an association between weight loss agents and liver enzyme elevation in men, particularly for traditional herbal medicines and dietary supplements. To confirm the observed associations, studies higher on the evidence hierarchy are needed., (© 2023. Springer Nature Limited.)

Psoriasis, a chronic and systemic inflammatory disorder characterized by activation of the interleukin (IL)-23/IL-17 axis, may be associated with the intestinal microbiota through the so-called "gut-skin axis." Clusterin is a glycoprotein ubiquitously distributed in mammalian tissues; however, its role in psoriasis is unclear. Therefore, we evaluated the role of clusterin in psoriatic skin inflammation, systemic inflammation, and colitis using a murine model of IMQ-induced psoriasis. In IMQ-treated clusterin-knockout (clusterin -/- ) mice, the expressions of inflammatory cytokines in clusterin-silenced human keratinocytes and intestinal microbial composition were analyzed. We also examined clusterin expression in the skin tissues of patients with psoriasis. IMQ-induced psoriatic skin inflammation is suppressed in clusterin -/- mice. Long-term administration of IMQ induced systemic inflammation and colitis; however, both were alleviated by the genetic deletion of clusterin. Genetic silencing of clusterin in human keratinocytes inhibited the production of inflammatory cytokines involved in the initiation and progression of psoriasis. The composition of the intestinal microbiota in IMQ-treated clusterin -/- and wild-type mice was different. Genetic deletion of clusterin suppressed the increase in the Firmicutes/Bacteroidetes (F/B) ratio. Skin tissues of patients with psoriasis showed high clusterin expression. In conclusion, inhibition of clusterin decreased psoriatic skin inflammation, systemic inflammation, colitis, and altered the F/B ratio in an IMQ-induced murine psoriasis model., (© 2023. Springer Nature Limited.)

A fast and straightforward fabrication process for producing a robust, flexible, and transparent conductive film was demonstrated using nanowelding of Ag nanowires through pressure-assisted microwave irradiation. This innovative process effectively reduces the sheet resistance of the Ag nanowire transparent conductive film without causing any thermal distortion to the PET substrate. The microwave irradiation induces nanowelding between Ag nanowires, leading to a decrease in sheet resistance by forming nanowelding junctions. This selective heating of Ag nanowires further enhances the reduction in sheet resistance. Additionally, the application of pressure-assisted microwave irradiation allows the Ag nanowires to be embedded into the PET substrate, resulting in the formation of a robust film capable of withstanding cycling bending stress. The pressure-assisted microwave irradiation process proves to be a strong fabrication method for creating Ag nanowire transparent conductive films, especially when dealing with thermally weak substrate materials., (© 2023. Springer Nature Limited.)

Aortic surgery is one of the most challenging types of surgeries, which is possibly related to cognitive sequelae. We aimed to investigate the changes in resting-state functional connectivity (rsFC) associated with intraoperative circulatory arrest (CA) in aortic surgery, exploring the relationship between the altered connectivity and postoperative cognitive functions. Thirty-eight patients participated in this study (14 with CA, 24 without). Functional magnetic resonance imaging was scanned on the fifth day after surgery or after the resolution of delirium if it was developed. We assessed the differences in the development of postoperative cognitive changes and rsFC between patients with and without CA. The occurrence of postoperative delirium and postoperative cognitive dysfunction was not significantly different between the patients with and without the application of CA. However, patients with CA showed increased in posterior cingulate cortex-based connectivity with the right superior temporal gyrus, right precuneus, and right hippocampus, and medial prefrontal cortex-based connectivity with the dorsolateral prefrontal cortex. The application of moderate hypothermic CA with unilateral antegrade cerebral perfusion is unlikely to affect aspects of postoperative cognitive changes, whereas it may lead to increased rsFC of the default mode network at a subclinical level following acute brain insults., (© 2023. Springer Nature Limited.)

Nephritis is common in systemic lupus erythematosus patients and is associated with hyper-activation of immune and renal cells. Although mesenchymal stem cells (MSCs) ameliorate nephritis by inhibiting T and B cells, whether MSCs directly affect renal cells is unclear. To address this issue, we examined the direct effect of MSCs on renal cells with a focus on chemokines. We found that expression of CCL2, CCL3, CCL4, CCL5, CCL8, CCL19, and CXCL10 increased 1.6-5.6-fold in the kidney of lupus-prone MRL.Fas lpr mice with advancing age from 9 to 16 weeks. Although MSCs inhibited the increase in the expression of most chemokines by 52-95%, they further increased CCL8 expression by 290%. Using renal cells, we next investigated how MSCs enhanced CCL8 expression. CCL8 was expressed by podocytes, but not by tubular cells. MSCs enhanced CCL8 expression by podocytes in a contact-dependent manner, which was proved by transwell assay and blocking with anti-VCAM-1 antibody. Finally, we showed that CCL8 itself activated MSCs to produce more immunosuppressive factors (IL-10, IDO, TGF-β1, and iNOS) and to inhibit more strongly IFN-γ production by T cells. Taken together, our data demonstrate that MSCs activate podocytes to produce CCL8 in a contact-dependent manner and conversely, podocyte-derived CCL8 might potentiate immunosuppressive activity of MSCs in a paracrine fashion. Our study documents a previously unrecognized therapeutic mechanism of MSCs in nephritis., (© 2023. Springer Nature Limited.)

Pretest probability (PTP) for assessing obstructive coronary artery disease (ObCAD) was updated to reduce overestimation. However, standard laboratory findings and electrocardiogram (ECG) raw data as first-line tests have not been evaluated for integration into the PTP estimation. Therefore, this study developed an ensemble model by adopting machine learning (ML) and deep learning (DL) algorithms with clinical, laboratory, and ECG data for the assessment of ObCAD. Data were extracted from the electronic medical records of patients with suspected ObCAD who underwent coronary angiography. With the ML algorithm, 27 clinical and laboratory data were included to identify ObCAD, whereas ECG waveform data were utilized with the DL algorithm. The ensemble method combined the clinical-laboratory and ECG models. We included 7907 patients between 2008 and 2020. The clinical and laboratory model showed an area under the curve (AUC) of 0.747; the ECG model had an AUC of 0.685. The ensemble model demonstrated the highest AUC of 0.767. The sensitivity, specificity, and F1 score of the ensemble model ObCAD were 0.761, 0.625, and 0.696, respectively. It demonstrated good performance and superior prediction over traditional PTP models. This may facilitate personalized decisions for ObCAD assessment and reduce PTP overestimation., (© 2023. Springer Nature Limited.)

Anti-thymocyte globulin (ATG) is currently the most widely prescribed induction regimen for preventing acute rejection after solid organ transplantation. However, the optimal dose of ATG induction regimen in Asian kidney recipients is unclear. Using the Korean Organ Transplantation Registry, we performed a retrospective cohort study of 4579 adult patients who received renal transplantation in South Korea and divided them into three groups according to the induction regimen: basiliximab group (n = 3655), low-dose ATG group (≤ 4.5 mg/kg; n = 467), and high-dose ATG group (> 4.5 mg/kg; n = 457). We applied the Toolkit for Weighting and Analysis of Nonequivalent Groups (TWANG) package to generate high-quality propensity score weights for intergroup comparisons. During four-year follow-ups, the high-dose ATG group had the highest biopsy-proven acute rejection rate (basiliximab 20.8% vs. low-dose ATG 22.4% vs. high-dose ATG 25.6%; P < 0.001). However, the rates of overall graft failure (4.0% vs. 5.0% vs. 2.6%; P < 0.001) and mortality (1.7% vs. 2.8% vs. 1.0%; P < 0.001) were the lowest in the high-dose ATG group. Our results show that high-dose ATG induction (> 4.5 mg/kg) was superior to basiliximab and low-dose ATG induction in terms of graft and patient survival in Asian patients undergoing kidney transplant., (© 2023. The Author(s).)

Neurodegenerative diseases are explained by progressive defects of cognitive function and memory. These defects of cognition and memory dysfunction can be induced by the loss of brain-derived neurotrophic factors (BDNF) signaling. Paeonia lactiflora is a traditionally used medicinal herb in Asian countries and some beneficial effects have been reported, including anti-oxidative, anti-inflammatory, anti-cancer activity, and potential neuroprotective effects recently. In this study, we found that suffruticosol A is a major compound in seeds of Paeonia lactiflora. When treated in a SH-SY5 cell line for measuring cell viability and cell survival, suffruticosol A increased cell viability (at 20 µM) and recovered scopolamine-induced neurodegenerative characteristics in the cells. To further confirm its neural amelioration effects in the animals, suffruticosol A (4 or 15 ng, twice a week) was administered into the third ventricle beside the brain of C57BL/6 mice for one month then the scopolamine was intraperitoneally injected into these mice to induce impairments of cognition and memory before conducting behavioral experiments. Central administration of suffruticosol A into the brain restored the memory and cognition behaviors in mice that received the scopolamine. Consistently, the central treatments of suffruticosol A showed rescued cholinergic deficits and BDNF signaling in the hippocampus of mice. Finally, we measured the long-term potentiation (LTP) in the hippocampal CA3-CA1 synapse to figure out the restoration of the synaptic mechanism of learning and memory. Bath application of suffruticosol A (40 µM) improved LTP impairment induced by scopolamine in hippocampal slices. In conclusion, the central administration of suffruticosol A ameliorated neuronal effects partly through elevated BDNF signaling., (© 2023. The Author(s).)

Insulin injections are stressful but necessary for people with diabetes. This study aimed to develop and validate the Distress of Self-Injection (DSI) scale for patients with diabetes aged ≥ 10 years. We created a questionnaire to evaluate DSI after examining each item following a literature review. The DSI scale with 20 questions in three domains (physical [4], psychosocial [7], and process [9]) was developed and tested at the Samsung Medical Center in Seoul, Korea, from April to September 2021. To verify structural validity, exploratory and confirmatory factor analyses (CFA) were conducted. Internal consistency was also calculated. To assess construct and criterion validity, the correlation between the DSI scale and Korean version of the Problem Areas in Diabetes (PAID-K) scale was obtained. Cronbach's alpha varied from 0.69 to 0.87, and the DSI score was 0.90, demonstrating acceptable internal consistency. CFA fit indices (CFI = 0.980; RMSEA = 0.033) were favorable. DSI and pertinent PAID-K domains correlated strongly. For measuring self-injection distress, the DSI score had good accuracy. For patients with diabetes aged ≥ 10 years who self-inject insulin, the DSI was a viable and accurate method for quantifying discomfort associated with insulin injection. Health practitioners should use the DSI to communicate with patients about their suffering., (© 2023. The Author(s).)

Conflicting studies exist on the association between menopausal hormone therapy (MHT) and skin cancers, such as melanoma and non-melanoma skin cancer (NMSC). This retrospective cohort study aimed to evaluate the risk of skin cancer from MHT using data from 2002 to 2019 from the National Health Insurance Service in South Korea. We included 192,202 patients with MHT and 494,343 healthy controls. Women > 40 years who had menopause between 2002 and 2011 were included. Patients with MHT had at least one MHT for at least 6 months and healthy controls had never been prescribed MHT agents. We measured the incidence of melanoma and NMSC. Melanoma developed in 70 (0.03%) patients with MHT and 249 (0.05%) controls, while the incidence of NMSC was 417 (0.22%) in the MHT group and 1680 (0.34%) in the controls. Tibolone (hazard ratio [HR] 0.812, 95% confidence interval [CI] 0.694-0.949) and combined oestrogen plus progestin by the manufacturer (COPM; HR 0.777, 95% CI 0.63-0.962) lowered the risk of NMSC, while other hormone groups did not change the risk. Overall, MHT was not associated with melanoma incidence in menopausal Korean women. Instead, tibolone and COPM were associated with a decrease in NMSC occurrence., (© 2023. The Author(s).)

Pelvic bone fracture is highly complex, and its anatomical reduction is difficult. Therefore, patient-specific customized plates have been developed using three-dimensional (3D) printing technology and are being increasingly used. In this study, the reduction status in five representative pelvic fracture models was compared between two groups: the 3D printing plate (3DP) group using a patient-specific 3D printed plate after virtual reduction and the conventional plate (CP) group using a conventional plate by manual bending. The 3DP and CP groups included 10 and 5 cases, respectively. The fractured models were reduced virtually and their non-locking metal plates were customized using 3D printing. The process of contouring the conventional plates to fit the contact surface of the bone with the bending tool was conducted by an experienced pelvic bone trauma surgeon. The reduction and fixation achieved using the two different plate groups was compared, and the significance of differences in the results was analyzed using paired t-tests, after verifying the normality of data distribution. The vertex distances between the surface of the bone and the contact surface of the plate were significantly lower in the 3DP group than in the CP group (0.407 ± 0.342 and 2.195 ± 1.643, respectively, P = 0.008). Length and angular variations, which are measurements of the reduction state, were also lower in the 3DP group than in the CP group (length variation: 3.211 ± 2.497 and 5.493 ± 3.609, respectively, P = 0.051; angular variation: 2.958 ± 1.977 and 4.352 ± 1.947, respectively, P = 0.037). The customized 3D printed plate in the virtual reduction model provided a highly accurate reduction of pelvic bone fractures, suggesting that the customized 3D printed plate may help ensure easy and accurate reduction., (© 2023. The Author(s).)

Dysphagia is a fatal condition after acute stroke. We established machine learning (ML) models for screening aspiration in patients with acute stroke. This retrospective study enrolled patients with acute stroke admitted to a cerebrovascular specialty hospital between January 2016 and June 2022. A videofluoroscopic swallowing study (VFSS) confirmed aspiration. We evaluated the Gugging Swallowing Screen (GUSS), an early assessment tool for dysphagia, in all patients and compared its predictive value with ML models. Following ML algorithms were applied: regularized logistic regressions (ridge, lasso, and elastic net), random forest, extreme gradient boosting, support vector machines, k-nearest neighbors, and naïve Bayes. We finally analyzed data from 3408 patients, and 448 of them had aspiration on VFSS. The GUSS showed an area under the receiver operating characteristics curve (AUROC) of 0.79 (0.77-0.81). The ridge regression model was the best model among all ML models, with an AUROC of 0.81 (0.76-0.86), an F1 measure of 0.45. Regularized logistic regression models exhibited higher sensitivity (0.66-0.72) than the GUSS (0.64). Feature importance analyses revealed that the modified Rankin scale was the most important feature of ML performance. The proposed ML prediction models are valid and practical for screening aspiration in patients with acute stroke., (© 2023. The Author(s).)

Gastric endoscopic resection (ER) is widely performed in Korea. This study aimed to investigate the overall status of gastric ER in Korea. We enrolled ESD or EMR cases performed for gastric cancer and adenoma from 2012 to 2017 by searching the NHIS database. The annual trend of gastric ER and the clinical characteristics were investigated. Institutions were classified into very high-, high-, low-, and very low volume centers (VHVC, HVC, LVC, and VLVC) by the procedure numbers, and institutional types, regional distributions, and medical resources were investigated accordingly. There were 175,370 ER cases during the study period, with an increasing trend over time. The average annual ESD procedure numbers were 3.9, 54.5, 249.5, and 540.3 cases in 131 VLVCs, 119 LVCs, 24 HVCs, and 12 VHVCs, respectively. Among ESD-performing institutions, 44.8% were located in the Seoul Capital Area. The distribution of medical resources showed a positive correlation with the procedural volume. Similar tendencies were also demonstrated in EMR, with some differences in hospital types and regional distribution. Gastric ER and ESD are increasing in Korea. There was a significant variance in the number of ER procedures and the distribution of types, regions, and medical resources according to the procedural volume., (© 2023. The Author(s).)

Pilot balloon palpation is still a commonly used method to evaluate cuff pressure of the endotracheal tube after intubation. This study determined whether the size of the tracheal tube influenced the accuracy of pilot balloon palpation. A prospective observational analysis of 208 patients intubated with an endotracheal tube of internal diameter (ID) 6.0 or 8.0 was conducted. An anesthesiologist judged the cuff pressure by manual pilot balloon palpation, and then measured the cuff pressure with a pressure gauge. Cuff pressure exceeding 20-30 cmH 2 O was defined as false recognition. The intracuff pressure was significantly higher in ID 6.0 tube than in the ID 8.0 tube (41.9 ± 18.8 cmH 2 O vs. 30.3 ± 11.9 cmH 2 O, p < 0.001). The number of patients that were mistakenly perceived to have appropriate cuff pressure by pilot balloon palpation was significantly higher in the ID 6.0 group compared to the ID 8.0 group (85 (81.7%) vs. 64 (61.5%), p = 0.001). Therefore, a smaller tube size may further increase risk of inaccurate measurement by pilot balloon palpation and although pressure gauge is recommended for all sizes to maximize accuracy, groups with increased risk factors should be targeted for standardized use of the pressure gauge., (© 2023. The Author(s).)

Acute myocardial infarction (AMI) is highly prevalent and remains the leading cause of mortality. Particularly in women, under-recognition and management of AMI have been raised. The aim of this study was to investigate the long-term trends of prevalence, treatment methodologies, and mortality of AMI by gender. The subjects of this study were patients hospitalized for AMI according to the Korean National Health Insurance Claims Database from 2002 to 2018. Total 633,097 AMI patients were hospitalized, 40% women. The incidence of AMI has been increasing since 2011, with a lower incidence in women. Overall, 53.1% of patients underwent CAG, with a lower tendency in women than in men (39.8% vs. 62.3%). Furthermore, fewer women underwent PCI than men (77.5% vs. 85.8% in 2018, p < 0.0001). Of the 336,463 AMI patients undergoing CAG, women were undertreated with a lower prescription rate of beta-blockers or statins at discharge. When adjusted for age, women showed higher 7-day mortality but lower 1-year mortality relative to men. According to the Korean National Health Insurance Claims Database, women with AMI have been under-recognized, underdiagnosed, and undertreated in terms of revascularization or medical therapy for years suggesting that efforts to close the gender gap are necessary., (© 2023. The Author(s).)

Epidermal growth factor receptor (EGFR) is an effective target for those patients with metastatic colorectal cancers that retain the wild-type RAS gene. However, its efficacy in many cancers, including bladder cancer, is unclear. Here, we studied the in vitro effects of cetuximab monoclonal antibodies (mAbs) targeting EGFR on the bladder cancer cells and role of CD46. Cetuximab was found to inhibit the growth of both colon and bladder cancer cell lines. Furthermore, cetuximab treatment inhibited AKT and ERK phosphorylation in the bladder cancer cells and reduced the expression of CD46 membrane-bound proteins. Restoration of CD46 expression protected the bladder cancer cells from cetuximab-mediated inhibition of AKT and ERK phosphorylation. We hypothesized that CD46 provides protection to the bladder cancer cells against mAb therapies. Bladder cancer cells were also susceptible to cetuximab-mediated immunologic anti-tumor effects. Further, cetuximab enhanced the cell killing by activating both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in bladder cancer cells. Restoration of CD46 expression protected the cells from both CDC and ADCC induced by cetuximab. Together, CD46 exhibited a cancer-protective effect against both direct (by involvement of PBMC or complement) and indirect cytotoxic activity by cetuximab in bladder cancer cells. Considering its clinical importance, CD46 could be an important link in the action mechanism of ADCC and CDC intercommunication and may be used for the development of novel therapeutic strategies., (© 2022. The Author(s).)

The early detection of graft failure in pediatric liver transplantation is crucial for appropriate intervention. Graft failure is associated with numerous perioperative risk factors. This study aimed to develop an individualized predictive model for 90-days graft failure in pediatric liver transplantation using machine learning methods. We conducted a single-center retrospective cohort study. A total of 87 liver transplantation cases performed in patients aged < 12 years at the Severance Hospital between January 2010 and September 2020 were included as data samples. Preoperative conditions of recipients and donors, intraoperative care, postoperative serial laboratory parameters, and events observed within seven days of surgery were collected as features. A least absolute shrinkage and selection operator (LASSO) -based method was used for feature selection to overcome the high dimensionality and collinearity of variables. Among 146 features, four variables were selected as the resultant features, namely, preoperative hepatic encephalopathy, sodium level at the end of surgery, hepatic artery thrombosis, and total bilirubin level on postoperative day 7. These features were selected from different times and represent distinct clinical aspects. The model with logistic regression demonstrated the best prediction performance among various machine learning methods tested (area under the receiver operating characteristic curve (AUROC) = 0.898 and area under the precision-recall curve (AUPR) = 0.882). The risk scoring system developed based on the logistic regression model showed an AUROC of 0.910 and an AUPR of 0.830. Together, the prediction of graft failure in pediatric liver transplantation using the proposed machine learning model exhibited superior discrimination power and, therefore, can provide valuable information to clinicians for their decision making during the postoperative management of the patients., (© 2022. The Author(s).)

This study aims to investigate health behaviors and psychological burdens in adolescent children of cancer parents. We compared health behaviors and mental health outcomes between 266 adolescent children with a parent diagnosed with cancer and 3163 control adolescents aged 12-19 years using data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2018. Alcohol use of adolescents increased between 2 and 5 years after parental cancer diagnosis (adjusted odds ratio [aOR], 1.72; 95% confidence interval [CI], 1.01-2.94) but decreased after 5 years. Parental cancer was associated with increased vaccination uptake in adolescents within 1 year of diagnosis (aOR, 3.19; 95% CI, 1.55-6.54), but after 2 years, there was no difference from rates in their peers. Maternal cancer was associated with increased depression among adolescents (aOR, 1.73; 95% CI, 1.10 - 2.73). Although the risks of suicidal thoughts/plans/attempts increased within 1 year after parental cancer diagnosis (aOR, 2.96; 95% CI, 1.00 - 8.83), it reduced 2 years after diagnosis, leading to no significant difference from the frequency in peers. Within five years after the parent was diagnosed with cancer, support for their adolescent children's health behaviors and mental health is necessary in the community., (© 2022. The Author(s).)

Flash-spun nonwoven (FS-NW) is gaining attention in the PPE field due to its excellent barrier and mechanical properties resulting from its non-uniform diameter distribution and unique filament morphology. The unique network structure of flash-spun filaments (FSF) comprising the FS-NW can be controlled by phase separation behavior in the supercritical fluid (SCF) process. This study proposes a simple method to control the microstructure of FSFs by controlling the pressure-induced phase separation (PIPS) process in polymer/SCF solution. This phase separation behavior of an HDPE/SCF solution was confirmed by using a high-pressure view cell. A multistage nozzle allowing for phase-separated pressure to form different phases was also designed. HDPE-FSFs were synthesized by flash-spinning, and their morphology, crystallinity, and mechanical properties were investigated. The results demonstrated that the filaments obtained by PSP control at 220 °C and with an HDPE concentration of 8 wt% showed a network structure composed of strands, wherein the diameters ranged from 1.39 to 40.9 μm. Optimal FSF was obtained at 76 bar, with a crystallinity of 64.0% and a tenacity of 2.88 g/d. The PIPS method can thus effectively control the microstructure more feasibly than temperature- or solvent-induced techniques and can allow the effective synthesis of various products., (© 2022. The Author(s).)

The waiting time for deceased donor kidney transplants (DDKT) is increasing. We evaluated DDKT prognosis according to the pretransplant dialysis vintage. A total of 4117 first-time kidney transplant recipients were enrolled from a prospective nationwide cohort in Korea. DDKT recipients were divided into tertiles according to pretransplant dialysis duration. Graft failure, mortality, and composite were compared between DDKT and living donor kidney transplant (LDKT) recipients. Pretransplant dialysis vintage was longer annually in DDKT recipients. In the subdistribution of the hazard model for the competing risk, the first tertile did not show an increased risk of graft failure compared with LDKT recipients; however, the second and third tertile groups had an increased risk of graft failure compared to LDKT recipients (adjusted hazard ratio [aHR] 3.59; 95% confidence interval [CI] 1.69-7.63; P < 0.001; aHR 2.37; 95% CI 1.06-5.33; P = 0.037). All DDKT groups showed a significantly higher risk of patient death than LDKT, with the highest risk in the third tertile group (aHR 11.12; 95% CI 4.94-25.00; P < 0.001). A longer pretransplant dialysis period was associated with a higher risk of the composite of patient death and graft failure in DDKT recipients. DDKT after a short period of dialysis had non-inferior results on graft survival compared with LDKT., (© 2022. The Author(s).)

Spectral-domain optical coherence tomography (SD-OCT) must accurately identify and measure the peripapillary retinal nerve fiber layer (pRNFL) thickness to improve the repeatability and reproducibility, and reduce measurement errors. Because Weiss ring can be located in front of the optic disc, we hypothesized that it may affect pRNFL thickness measurements obtained using SD-OCT. We retrospectively reviewed the medical records of patients with (group W) and without (group N) Weiss ring, observed on OCT fundus image and an RNFL map devised using SD-OCT. Optic disc cube scans (200 × 200) were obtained to measure pRNFL thicknesses (superior, temporal, inferior, nasal, and average) at two consecutive visits. Pearson's correlation coefficient (r), intraclass correlation coefficient (ICC), and coefficient of variation (CV) were calculated. The r and ICC values for the pRNFL thickness measurements at the two visits were lower for group W compared to group N, but statistical significance was reached only for inferior pRNFL thickness. In addition, CV values were greater for group W compared to group N, but the differences were significant only for inferior and average pRNFL thickness measurements (p < 0.001 and p = 0.004, respectively). Weiss ring located near the optic disc can affect pRNFL thickness measurements and repeatability thereof, especially the inferior quadrant and average values. Therefore, it is important to identify the presence of Weiss ring when analyzing pRNFL thickness values., (© 2022. The Author(s).)

We aimed to investigate the predictive value of preoperative clinical factors and dopamine transporter imaging for outcomes after globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with advanced Parkinson's disease (PD). Thirty-one patients with PD who received bilateral GPi DBS were included. The patients underwent preoperative [ 18 F] FP-CIT positron emission tomography before DBS surgery. The Unified Parkinson's Disease Rating Scale (UPDRS) were used to assess outcomes 12 months after DBS. Univariate and multivariate linear regression analysis were performed to investigate the association between clinical variables including sex, age at onset of PD, disease duration, cognitive status, preoperative motor severity, levodopa responsiveness, daily dose of dopaminergic medication, and dopamine transporter availability in the striatum and outcomes after GPi DBS. Younger age at onset of PD was associated with greater DBS motor responsiveness and lower postoperative UPDRS III score. Greater levodopa responsiveness, lower preoperative UPDRS III score and lower striatal dopamine transporter availability were associated with lower postoperative UPDRS III score. Younger age at onset was also associated with greater decrease in UPDRS IV score and dyskinesia score after GPi DBS. Our results provide useful information to select DBS candidates and predict therapeutic outcomes after GPi DBS in advanced PD., (© 2022. The Author(s).)

Model Dermatology ( https://modelderm.com ; Build2021) is a publicly testable neural network that can classify 184 skin disorders. We aimed to investigate whether our algorithm can classify clinical images of an Internet community along with tertiary care center datasets. Consecutive images from an Internet skin cancer community ('RD' dataset, 1,282 images posted between 25 January 2020 to 30 July 2021; https://reddit.com/r/melanoma ) were analyzed retrospectively, along with hospital datasets (Edinburgh dataset, 1,300 images; SNU dataset, 2,101 images; TeleDerm dataset, 340 consecutive images). The algorithm's performance was equivalent to that of dermatologists in the curated clinical datasets (Edinburgh and SNU datasets). However, its performance deteriorated in the RD and TeleDerm datasets because of insufficient image quality and the presence of out-of-distribution disorders, respectively. For the RD dataset, the algorithm's Top-1/3 accuracy (39.2%/67.2%) and AUC (0.800) were equivalent to that of general physicians (36.8%/52.9%). It was more accurate than that of the laypersons using random Internet searches (19.2%/24.4%). The Top-1/3 accuracy was affected by inadequate image quality (adequate = 43.2%/71.3% versus inadequate = 32.9%/60.8%), whereas participant performance did not deteriorate (adequate = 35.8%/52.7% vs. inadequate = 38.4%/53.3%). In this report, the algorithm performance was significantly affected by the change of the intended settings, which implies that AI algorithms at dermatologist-level, in-distribution setting, may not be able to show the same level of performance in with out-of-distribution settings., (© 2022. The Author(s).)