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Abstract The relationship between obstructive sleep apnea (OSA) and chronic rhinosinusitis (CRS) has not yet been fully elucidated. Therefore, the objective of this study was to evaluate the connection between OSA risk and CRS by investigating associations between the STOP-Bang questionnaire and presence of CRS in a nationwide, population-based study. This is a cross-sectional study based on the Korean National Health and Nutrition Examination Survey (KNHANES). We evaluated 10,081 subjects who completed both the STOP-Bang and CRS-related questionnaires. Among the total subjects, 390 (3.9%) were CRS patients. The median STOP-Bang score was 3.0 [2.0; 4.0] in CRS patients, compared to 2.0 [1.0; 3.0] in subjects without CRS. In a low-risk group according to the STOP-Bang questionnaire, 3.1% of subjects were CRS patients. However, a gradual increase was observed among different risk groups. In the higher risk group, CRS patients accounted for 5.3% (P

Abstract The SARS-CoV-2 pandemic has had an unprecedented impact on global public health and the economy. Although vaccines and antivirals have provided effective protection and treatment, the development of new small molecule-based antiviral candidates is imperative to improve clinical outcomes against SARS-CoV-2. In this study, we identified UNI418, a dual PIKfyve and PIP5K1C inhibitor, as a new chemical agent that inhibits SARS-CoV-2 entry into host cells. UNI418 inhibited the proteolytic activation of cathepsins, which is regulated by PIKfyve, resulting in the inhibition of cathepsin L-dependent proteolytic cleavage of the SARS-CoV-2 spike protein into its mature form, a critical step for viral endosomal escape. We also demonstrated that UNI418 prevented ACE2-mediated endocytosis of the virus via PIP5K1C inhibition. Our results identified PIKfyve and PIP5K1C as potential antiviral targets and UNI418 as a putative therapeutic compound against SARS-CoV-2.

Abstract Background Obesity has been suggested to be associated with the coronavirus disease 2019 (COVID-19); however, it is unclear whether obesity or metabolic abnormalities accompanied by obesity have a stronger association with COVID-19 risk. Methods This study used the Korea Disease Control and Prevention Agency database, which includes information about the COVID-19 diagnosis and mortality dates of the entire Korean population between October 2020 and December 2021 (for diagnosis) or March 2022 (for mortality). A total of 24,310,283 adults were included and classified into four metabolic obesity phenotypes: (1) metabolically healthy and normal weight (MHNW), (2) metabolically unhealthy and normal weight (MUNW), (3) metabolically healthy and obese (MHO), and (4) metabolically unhealthy and obese (MUO). COVID-19 mortality and severity were compared according to metabolic obesity phenotypes in the total population and in each age group (20–

Abstract The mass production of high-quality graphene is required for industrial application as a future electronic material. However, the chemical vapor deposition (CVD) systems previously studied for graphene production face bottlenecks in terms of quality, speed, and reproducibility. Herein, we report a novel conveyor CVD system that enables rapid graphene synthesis using liquid precursors. Pristine and nitrogen-doped graphene samples of a size comparable to a smartphone (15 cm × 5 cm) are successfully synthesized at temperatures of 900, 950, and 1000 °C using butane and pyridine, respectively. Raman spectroscopy allows optimization of the rapid-synthesis conditions to achieve uniformity and high quality. By conducting compositional analysis via X-ray photoelectron spectroscopy as well as electrical characterization, it is confirmed that graphene synthesis and nitrogen doping degree can be adjusted by varying the synthesis conditions. Testing the corresponding graphene samples as gas-sensor channels for NH3 and NO2 and evaluating their response characteristics show that the gas sensors exhibit polar characteristics in terms of gas adsorption and desorption depending on the type of gas, with contrasting characteristics depending on the presence or absence of nitrogen doping; nitrogen-doped graphene exhibits superior gas-sensing sensitivity and response speed compared with pristine graphene.

Abstract Patients with mental illnesses, particularly psychosis and obsessive‒compulsive disorder (OCD), frequently exhibit deficits in executive function and visuospatial memory. Traditional assessments, such as the Rey‒Osterrieth Complex Figure Test (RCFT), performed in clinical settings require time and effort. This study aimed to develop a deep learning model using the RCFT and based on eye tracking to detect impaired executive function during visuospatial memory encoding in patients with mental illnesses. In 96 patients with first-episode psychosis, 49 with clinical high risk for psychosis, 104 with OCD, and 159 healthy controls, eye movements were recorded during a 3-min RCFT figure memorization task, and organization and immediate recall scores were obtained. These scores, along with the fixation points indicating eye-focused locations in the figure, were used to train a Long Short-Term Memory + Attention model for detecting impaired executive function and visuospatial memory. The model distinguished between normal and impaired executive function, with an F 1 score of 83.5%, and identified visuospatial memory deficits, with an F 1 score of 80.7%, regardless of psychiatric diagnosis. These findings suggest that this eye tracking-based deep learning model can directly and rapidly identify impaired executive function during visuospatial memory encoding, with potential applications in various psychiatric and neurological disorders.

This paper presents a computational framework for drop time assessment of a control element assembly (CEA) under fuel assembly (FA) deformations. The proposed framework consists of three key components: 1) finite element modeling of CEA, 2) fluid-structure interaction to compute drag force, and 3) modeling of frictional contact between CEA and FA. Specially, to accommodate the large motion of CEA, beam elements based on absolute nodal coordinate formulation (ANCF) are adopted. The continuity equation is utilized to calculate the drag force, considering flow changes in the cross-sectional area during the CEA drop. Lastly, beam-inside-beam frictional contact model is employed to capture practical contact conditions between CEA and FA. The proposed framework is validated through experiments under two scenarios: free falls of CEA within FA, encompassing undeformed and deformed scenarios. The experimental validation of the framework demonstrated that the drop time of CEA can be accurately predicted under the complex coupling effects of fluid and frictional contact. The drop times of the S-shaped deformation case is longer than those of the C-shaped deformation case, affirming the time delay due to frictional force. The validation confirms the potential applicability to access the safety and reliability of nuclear power plants under extreme conditions.

Background/purpose: The retrograde filling material, particularly mineral trioxide aggregate (MTA) employed in apicoectomy, should possess high antibacterial efficacy and osteogenic potential. We evaluated the antibacterial efficacy, biocompatibility, and osteogenic potential following the addition of silver nanoparticles (AgNPs) and calcium fluoride (CaF2) in retrograde filling material of MTA. Materials and methods: MTA was mixed with four different solvents. Group 1 (G1): distilled water, Group 2 (G2): 50 ppm AgNPs, Group 3 (G3): 1 wt% CaF2, and Group 4 (G4): 50 ppm AgNPs and 1 wt% CaF2. The pH variation of each group was monitored, while the surface roughness was measured. The antibacterial efficacy against Enterococcus faecalis (E. faecalis) and the viability of murine pre-osteoblast (MC3T3) were evaluated for each group using colorimetric assays. The gene expression levels of osteogenic potential marker (OCN, ALPL, and RUNX2) in MC3T3 cells for each group were quantified using real-time-qPCR. Statistical analysis was performed at α = 0.05 level of significance. Results: When comparing the levels of antibacterial efficacy, the order of effectiveness was G4>G2>G3>G1 (P

Background/purpose: In the field of conservative dentistry and endodontics, mineral trioxide aggregate (MTA), commonly used, possesses advantages such as biocompatibility, antimicrobial properties and osteogenic potential. This study investigated the feasibility of utilizing membrane form mineral trioxide aggregate (MTA) as a barrier membrane in guided bone regeneration (GBR) procedures. Materials and methods: Membranes were electrospun from three different formulations: 15 w/v% Polycaprolactone (PCL), 13 w/v% PCL + 2 w/v% MTA (2MTA), and 11 w/v% PCL + 4 w/v% MTA (4MTA). Physicochemical and mechanical properties of the electrospun membrane were compared, encompassing parameters such as surface morphology, fiber diameter distribution, chemical composition, phase identification, tensile stress, pH variation, and water contact angle. Moreover, the antimicrobial properties against of the electrospun membranes were assessed through direct exposure to streptococcus aureus (S. aureus) and candida albicans (C. albicans). Additionally, on the 7th day, biocompatibility and cell attachment were investigated with respect to L929 (fibroblast) and MC3T3 (pre-osteoblast) cells. Inhibition of L929 cell infiltration and the expression of osteogenic related genes including osteocalcin (OCN), alkaline phosphatase (ALP), and runt related transcription factor 2 (RUNX2) in MC3T3 cells on 7th and 14th days were also investigated. Results: PCL, 2MTA, and 4MTA exhibited no statistically differences in fiber diameter distribution and tensile stress. However, as the MTA content increased, wettability and pH also increased. Due to the elevated pH, 4MTA demonstrated the lowest viability S.aureus and C.albicans. All membranes were highly biocompatibility and promoted cell attachment, while effectively preventing L929 cell infiltration. Lastly 4MTA showed increase in OCN, ALP, and RUNX2 expression on both 7th and 14th day. Conclusion: The membrane form MTA possessed characteristics essential for a novel barrier membrane.

Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disease that may be associated with hypertension, autoregulatory failure, and the use of calcineurin inhibitors following heart transplantation (HT). In this article, we present a case series of PRES, discussing its potential causes and management strategies. Among the 126 HT recipients at our hospital, four were diagnosed with PRES. Three of these patients developed PRES within 7 days after HT. Prior to the onset of PRES, all patients experienced sustained hypertension, and strict blood pressure (BP) control was maintained. Three of the four patients recovered without PRES recurrence, while one patient died of sepsis after an episode of altered consciousness. Hypertension was observed in all patients prior to the onset of PRES, and the majority experienced symptom improvement with BP control. While most cases of PRES were reversible with conservative treatment, including the administration of antiepileptics, one irreversible case resulted in in-hospital mortality. Thus, PRES can have serious outcomes and is not invariably benign.

Abstract MraY (phospho-N-acetylmuramoyl-pentapeptide-transferase) inhibitory natural products are attractive molecules as candidates for a new class of antibacterial agents to combat antimicrobial-resistant bacteria. Structural optimization of these natural products is required to improve their drug-like properties for therapeutic use. However, chemical modifications of these natural products are painstaking tasks due to complex synthetic processes, which is a bottleneck in advancing natural products to the clinic. Here, we develop a strategy for a comprehensive in situ evaluation of the build-up library, which enables us to streamline the preparation of the analogue library and directly assess its biological activities. We apply this approach to a series of MraY inhibitory natural products. Through construction and evaluation of the 686-compound library, we identify promising analogues that exhibit potent and broad-spectrum antibacterial activity against highly drug-resistant strains in vitro as well as in vivo in an acute thigh infection model. Structures of the MraY-analogue complexes reveal distinct interaction patterns, suggesting that these analogues represent MraY inhibitors with unique binding modes. We further demonstrate the generality of our strategy by applying it to tubulin-binding natural products to modulate their tubulin polymerization activities.

Abstract Background Extramammary Paget’s disease (EMPD) is a rare cancer that occurs within the epithelium of the skin, arising predominantly in areas with high apocrine gland concentration such as the vulva, scrotum, penis and perianal regions. Here, we aim to integrate clinicopathological data with genomic analysis of aggressive, rapidly-progressing de novo metastatic EMPD responding to HER2-directed treatment in combination with other agents, to attain a more comprehensive understanding of the disease landscape. Methods Immunohistochemical staining on the scrotal wall tumor and bone marrow metastasis demonstrated HER2 overexpression. Whole genome sequencing of the tumor and matched blood was performed. Results Notable copy number gains (log2FC > 0.9) on chromosomes 7 and 8 were detected (n = 81), with 92.6% of these unique genes specifically located on chromosome 8. Prominent cancer-associated genes include ZNF703, HOOK3, DDHD2, LSM1, NSD3, ADAM9, BRF2, KAT6A and FGFR1. Interestingly, ERBB2 gene did not exhibit high copy number gain (log2FC = 0.4) although 90% of tumor cells stained HER2-positive. Enrichment in pathways associated with transforming growth factor-beta (TGFβ) (FDR = 0.0376, Enrichment Ratio = 8.12) and fibroblast growth factor receptor (FGFR1) signaling (FDR = 0.0082, Enrichment Ratio = 2.3) was detected. Amplicon structure analysis revealed that this was a simple-linear amplification event. Conclusion Whole genome sequencing revealed the underlying copy number variation landscape in HER2-positive metastatic EMPD. The presence of alternative signalling pathways and genetic variants suggests potential interactions with HER2 signalling, which possibly contributed to the HER2 overexpression and observed response to HER2-directed therapy combined with other agents in a comprehensive treatment regimen.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Abstract Although bevacizumab (BVZ), a representative drug for anti-angiogenesis therapy (AAT), is used as a first-line treatment for patients with glioblastoma (GBM), its efficacy is notably limited. Whereas several mechanisms have been proposed to explain the acquisition of AAT resistance, the specific underlying mechanisms have yet to be sufficiently ascertained. Here, we established that inhibitor of differentiation 1 (ID1)high/activin Ahigh glioblastoma cell confers resistance to BVZ. The bipotent effect of activin A during its active phase was demonstrated to reduce vasculature dependence in tumorigenesis. In response to a temporary exposure to activin A, this cytokine was found to induce endothelial-to-mesenchymal transition via the Smad3/Slug axis, whereas prolonged exposure led to endothelial apoptosis. ID1 tumors showing resistance to BVZ were established to be characterized by a hypovascular structure, hyperpermeability, and scattered hypoxic regions. Using a GBM mouse model, we demonstrated that AAT resistance can be overcome by administering therapy based on a combination of BVZ and SB431542, a Smad2/3 inhibitor, which contributed to enhancing survival. These findings offer valuable insights that could contribute to the development of new strategies for treating AAT-resistant GBM.

Background The prognostic implication of mildly reduced ejection fraction (mrEF) after acute myocardial infarction has not been clearly demonstrated. We investigated the long‐term risk of cardiovascular death and its predictors in patients with mrEF following acute myocardial infarction. Methods and Results A total of 18 668 patients who presented with acute myocardial infarction were included in 2 prospective, multicenter registries. The incidence of adverse cardiovascular events according to the left ventricular ejection fraction (EF) strata at index admission were evaluated. A score system consisting of clinical variables were developed to predict long‐term cardiovascular death in the mrEF group. There were 2548 patients with reduced EF (EF ≤40%), 4266 patients with mrEF (EF 41%–49%), and 11 854 patients with preserved EF (EF ≥50%). During a median follow‐up period of 37.9 months, the cardiovascular death rate was 22.3% in the reduced EF group, 10.3% in the mrEF group, and 7.3% in the preserved EF group (P65 years, hypertension, stroke, severe renal insufficiency, and Killip class ≥3 were independent predictors for cardiovascular death. Presence of >2 predictors best discriminated the high‐risk patients for cardiovascular death with an area under the curve of 0.746. Incidence of cardiovascular death in the high‐risk mrEF group was comparable with the rEF group, while it was lower in the low‐risk mrEF group than in the pEF group. Conclusions Patients with mrEF after acute myocardial infarction had a modest risk of cardiovascular death. Clinical predictors could help discriminate a high‐risk subpopulation with cardiovascular death risks comparable with those in the reduced EF group.

Tuning the color of Au has been a longstanding problem in the luxury industry. Conventional approaches, involving Au alloying, compromise purity and demand distinct alloy compositions for each hue. This study demonstrates a lithography‐free method for generating structural colors on a gold surface by adjusting the thickness of titanium dioxide, a high‐index dielectric. While color tuneability is limited if TiO2 is coated directly on the Au surface, a range of vivid colors can be generated if a 50−100 nm thick AuAl2 underlayer is used. AuAl2, an accepted alloy for purple gold, broadens the color gamut, providing a protective coating without diminishing gold purity. The reflectance dip of the bilayer structure exhibits a significant red shift with increasing thickness of the TiO2 layer, allowing diverse colors by TiO2 insulator tuning. Simulation studies corroborate experimental results, affirming that coating a TiO2 layer on the AuAl2 underlayer yields a wide range of colors. This method, based on thin‐film interference, shows promise for widespread use, offering a broad spectrum of structural colors in an industry striving for diverse Au color representation.

As genomic selection emerges as a promising breeding method for both plants and animals, numerous methods have been introduced and applied to various real and simulated data sets. Research suggests that no single method is universally better than others; rather, performance is highly dependent on the characteristics of the data and the nature of the prediction task. This implies that each method has its strengths and weaknesses. In this study, we exploit this notion and propose a different approach. Rather than comparing multiple methods to determine the best one for a particular study, we advocate combining multiple methods to achieve better performance than each method in isolation. In pursuit of this goal, we introduce and develop a computational method of the stacked generalization within ensemble methods. In this method, the meta-model merges predictions from multiple base models to achieve improved performance. We applied this method to plant and animal data and compared its performance with currently available methods using standard performance metrics. We found that the proposed method yielded a lower or comparable mean squared error in predicting phenotypes compared to the current methods. In addition, the proposed method showed greater resistance to overfitting compared to the current methods. Further analysis included statistical hypothesis testing, which showed that the proposed method outperformed or matched the current methods. In summary, the proposed stacked generalization integrates currently available methods to achieve stable and better performance. In this context, our study provides general recommendations for effective practices in genomic selection.

Summary: The ability to sense and respond to osmotic fluctuations is critical for the maintenance of cellular integrity. We used gene co-essentiality analysis to identify an unappreciated relationship between TSC22D2, WNK1, and NRBP1 in regulating cell volume homeostasis. All of these genes have paralogs and are functionally buffered for osmo-sensing and cell volume control. Within seconds of hyperosmotic stress, TSC22D, WNK, and NRBP family members physically associate into biomolecular condensates, a process that is dependent on intrinsically disordered regions (IDRs). A close examination of these protein families across metazoans revealed that TSC22D genes evolved alongside a domain in NRBPs that specifically binds to TSC22D proteins, which we have termed NbrT (NRBP binding region with TSC22D), and this co-evolution is accompanied by rapid IDR length expansion in WNK-family kinases. Our study reveals that TSC22D, WNK, and NRBP genes evolved in metazoans to co-regulate rapid cell volume changes in response to osmolarity.

BackgroundThe alpha-protein kinase 3 (ALPK3) gene (OMIM: 617608) is associated with autosomal recessive familial hypertrophic cardiomyopathy-27 (CMH27, OMIM: 618052). Recently, several studies have shown that monoallelic premature terminating variants (PTVs) in ALPK3 are associated with adult-onset autosomal dominant hypertrophic cardiomyopathy (HCMP). However, these studies were performed on patient cohorts mainly from European Caucasian backgrounds.MethodsTo determine if this finding is replicated in the Korean HCMP cohort, we evaluated 2,366 Korean patients with non-syndromic HCMP using exome sequencing and compared the cohort dataset with three independent population databases.ResultsWe observed that monoallelic PTVs in ALPK3 were also significantly enriched in Korean patients with HCMP with an odds ratio score of 10–21.ConclusionsWe suggest that ALPK3 PTV carriers be considered a risk group for developing HCMP and be monitored for cardiomyopathies.

Many countries are actively promoting a community solar program, which is a community energy program centered on solar photovoltaic power generation, as a public participation-type energy policy. In this study, we analyze the preferences of potential participants in community solar programs from the perspective of policymakers to identify public acceptance and draw policy implications. As a methodology, the choice experiment with a stated preference method is used to analyze the preferences on the individual attributes of community solar energy in terms of business model targeting Korean who are the potential participants. Furthermore, we observed the homogeneity of preferences within each group and the heterogeneity of preferences between groups by dividing the groups based on the latent class model estimation. The results of this study show that the attributes of the community solar program, such as the operating agent, contract period, expected return, and participatory management, have a significant impact on the acceptance of potential consumers, and that there are clear differences between potential classes. The results can be used as basic data for the community energy projects and can contribute to designing succecesful energy policies not only for Korea but also for governments of other countries pursuing carbon neutrality.

Purpose We assessed the effectiveness and safety of using intravesical onabotulinumtoxinA (onabotA; BOTOX) injection with a low dose (75 units) for treating urinary storage symptoms in patients with detrusor overactivity with detrusor underactivity (DODU) compared to using the standard 100 units of onabotA in patients with overactive bladder (OAB). Methods This ambidirectional study included 121 female patients who received intravesical onabotA injections at our hospitals. A total of 87 patients with OAB and 34 patients with DODU were reviewed using a 3-day voiding diary, uroflowmetry, and questionnaires including the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score, and Patient Perception of Bladder Condition. Patients were evaluated at baseline, within 2 weeks of treatment, and beyond 3 months after treatment. Results Questionnaire scores of the DODU group demonstrated significant improvement in the short term, with a subsequent decline, but an overall improvement compared to baseline in the long term. Notably, the DODU group exhibited enhanced IPSS voiding scores after the treatment. In the OAB group, most questionnaire scores, excluding the IPSS voiding score, showed significant posttreatment improvement, which was sustained to some extent in the long term. Voiding diary parameters related to storage symptoms were enhanced in both groups. The maximum and mean flow rates decreased in the OAB group but increased in the DODU group, particularly in the short term (P=0.000). The postvoid residual volume increased in both groups after posttreatment, with a mitigated change in the long term. Safety assessments revealed manageable adverse events in both groups with comparable frequencies. Conclusions Low-dose intravesical onabotA for DODU demonstrated a relatively shorter duration of efficacy than OAB. Nonetheless, the treatment improved both storage and voiding symptoms in patients with DODU without significant adverse effects.

Abstract This study develops a solution to sports match-fixing using various machine-learning models to detect match-fixing anomalies, based on betting odds. We use five models to distinguish between normal and abnormal matches: logistic regression (LR), random forest (RF), support vector machine (SVM), the k-nearest neighbor (KNN) classification, and the ensemble model—a model optimized from the previous four. The models classify normal and abnormal matches by learning their patterns using sports betting odds data. The database was developed based on the world football league match betting data of 12 betting companies, which offered a vast collection of data on players, teams, game schedules, and league rankings for football matches. We develop an abnormal match detection model based on the data analysis results of each model, using the match result dividend data. We then use data from real-time matches and apply the five models to construct a system capable of detecting match-fixing in real time. The RF, KNN, and ensemble models recorded a high accuracy, over 92%, whereas the LR and SVM models were approximately 80% accurate. In comparison, previous studies have used a single model to examine football match betting odds data, with an accuracy of 70–80%.

Non-gonococcal sexually transmitted infections (STIs) include chlamydia, syphilis, and chancroids. Chlamydia is the most common STI caused by Chlamydia trachomatis and is mainly transmitted through sexual intercourse or vertical transmission at birth. Although symptoms are mostly absent or mild, untreated chlamydial infections in females can lead to pelvic inflammatory disease, chronic pelvic pain, and infertility due to the narrowing of fallopian tubes. Syphilis is caused by Treponema pallidum and is divided into phase I, phase II, latent syphilis, and phase III. The incidence of syphilis, including congenital syphilis, has significantly increased in the United States in recent years. The chronic status of this disease can significantly increase morbidity and potentially affect almost all body organs, which, in rare cases, can lead to death. Additionally, untreated maternal syphilis can lead to fetal death and fatal congenital infections in newborns. Chancroid is an STI caused by Haemophilus ducreyi, and its prevalence is gradually decreasing in Korea and worldwide. The symptoms include shallow genital ulcers with suppurative granulomatous inflammation and tender inguinal lymphadenopathy. Chancroids can be differentiated from syphilitic chancres based on their appearance. In contrast to painless chancres, chancroids are painful. Ureaplasma urealyticum, Ureaplasma parvum, and Mycoplasma hominis are considered symbiotic bacteria. Infections caused by these bacteria are usually not considered STIs and do not require treatment unless they are suspected of being associated with infertility. This article presents the 2023 Korean STI guidelines for non-gonococcal bacterial infections.

Background/Aims The prognosis of patients with idiopathic pulmonary fibrosis (IPF) and respiratory failure requiring mechanical ventilation is poor. Therefore, mechanical ventilation is not recommended. Recently, outcomes of mechanical ventilation, including those for patients with IPF, have improved. The aim of this study was to investigate changes in the use of mechanical ventilation in patients with IPF and their outcomes over time. Methods This retrospective, observational cohort study used data from the National Health Insurance Service database. Patients diagnosed with IPF between January 2011 and December 2019 who were placed on mechanical ventilation were included. We analyzed changes in the use of mechanical ventilation in patients with IPF and their mortality using the Cochran-Armitage trend test. Results Between 2011 and 2019, 1,227 patients with IPF were placed on mechanical ventilation. The annual number of patients with IPF with and without mechanical ventilation increased over time. However, the ratio was relatively stable at approximately 3.5%. The overall hospital mortality rate was 69.4%. There was no improvement in annual hospital mortality rate. The overall 30-day mortality rate was 68.7%, which did not change significantly. The overall 90-day mortality rate was 85.3%. The annual 90-day mortality rate was decreased from 90.9% in 2011 to 83.1% in 2019 (p = 0.028). Conclusions Despite improvements in intensive care and ventilator management, the prognosis of patients with IPF receiving mechanical ventilation has not improved significantly.

Abstract Osteoarthritis (OA) is a progressive and irreversible degenerative joint disease that is characterized by cartilage destruction, osteophyte formation, subchondral bone remodeling, and synovitis. Despite affecting millions of patients, effective and safe disease-modifying osteoarthritis drugs are lacking. Here we reveal an unexpected role for the small molecule 5-aminosalicylic acid (5-ASA), which is used as an anti-inflammatory drug in ulcerative colitis. We show that 5-ASA competes with extracellular-matrix collagen-II to bind to osteoclast-associated receptor (OSCAR) on chondrocytes. Intra-articular 5-ASA injections ameliorate OA generated by surgery-induced medial-meniscus destabilization in male mice. Significantly, this effect is also observed when 5-ASA was administered well after OA onset. Moreover, mice with DMM-induced OA that are treated with 5-ASA at weeks 8–11 and sacrificed at week 12 have thicker cartilage than untreated mice that were sacrificed at week 8. Mechanistically, 5-ASA reverses OSCAR-mediated transcriptional repression of PPARγ in articular chondrocytes, thereby suppressing COX-2-related inflammation. It also improves chondrogenesis, strongly downregulates ECM catabolism, and promotes ECM anabolism. Our results suggest that 5-ASA could serve as a DMOAD.

Purpose Since the introduction of robotic surgery, robots for colorectal cancer have replaced laparoscopic surgery, and a single-port robot (SPR) platform has been launched and is being used to treat patients. We analyzed the learning curve and initial complications of using an SPR platform in colorectal cancer surgery. Methods We reviewed 39 patients who underwent SPR colectomy from April to October 2019. All surgeries were performed by the same surgeon using an SPR device. A learning curve was generated using the cumulative sum methodology to assess changes in total operation time, docking time, and surgeon console time. We grouped the patients into 3 groups according to the time period: the first 11 were phase 1, the next 11 were phase 2, and the last 17 were phase 3. Results The mean age of the patients was 61.28±13.03 years, and they had a mean body mass index of 23.79±2.86 kg/m2. Among the patients, 23 (59.0%) were male, and 16 (41.0%) were female. The average operation time was 186.59±51.30 minutes, the average surgeon console time was 95.49±35.33 minutes, and the average docking time (time from skin incision to robot docking) was 14.87±10.38 minutes. The surgeon console time differed significantly among the different phases (P

This review examined and analyzed clinical research trends in the treatment of compression fractures in traditional Korean medicine using case studies. Accordingly, 5 web databases were searched using relevant Korean and English terms. Based on predefined exclusion and inclusion criteria, 16 case studies were selected, analyzed, and classified according to the journal, publication year, participants, chief complaints, affected vertebrae, treatment and evaluation methods, and improvement. The case studies reported various treatment methods, including acupuncture, herbal medicine, physical therapy, cupping, moxibustion, and band training. All 16 case studies reported the use of combination therapy. All 23 cases reported in these case studies demonstrated improvement in chief complaints, and none reported any side effects.

Bumblebees (B. terrestris) play a crucial role as highly efficient biological agents in commercial pollination. Understanding the molecular mechanisms governing their adaptation to diverse seasonal environments may pave the way for effective management strategies in the future. With the burgeoning advancement in post-genetic studies focusing on B. terrestris, there is a critical need to normalize quantitative real-time PCR (qRT-PCR) data using suitable reference genes. To address this necessity, we employed RefFinder, a software-based tool, to assess the suitability of several candidate endogenous control genes, including actin (ACT), arginine kinase (AK), elongation factor 1 alpha (EF1), glyceraldehyde-3-phosphate (GAPDH), phospholipase (PLA2), and ribosomal proteins (S18, S28). These genes were evaluated for their efficacy as biological endogenous controls by examining their expression patterns across various environmental conditions corresponding to different seasons (Spring, Summer, Autumn, Winter) and tissues (ovary, fat body, thorax, head) in bumblebees. Moreover, the study investigated the significance of selecting appropriate reference genes for three key genes involved in the juvenile hormone (JH) signaling pathways: Krüppel homolog 1 (Kr-h1), methyl farnesoate epoxidase (MFE), and Vitellogenin (Vg). Our research identifies specific genes suitable for normalization in B. terrestris, thereby offering valuable insights into gene expression and functional metabolic genetics under varying seasonal conditions. This catalog of reference genes will serve as a valuable resource for future research endeavors.

Abstract Background About 3%–5% of non‐small cell lung cancer (NSCLC) presents positive anaplastic lymphoma kinase (ALK). Recently, several target agents have been approved as a treatment for ALK‐positive NSCLC. This study aimed to analyze the real‐world efficacy and outcome when administered crizotinib, the first approved target agent for ALK‐positive NSCLC, according to first‐ or late‐line treatment. Methods A total of 290 patients with ALK‐positive advanced NSCLC who were treated with crizotinib in 15 institutions in South Korea from January 2009 to December 2018 were enrolled. Results The median age of patients was 57.0 years, and 50.3% were male. The median follow‐up duration was 29.3 months. Among them, 113 patients received crizotinib as first‐line therapy. The objective response rate (ORR) was 60.1% (57.0% for first‐line recipients, 61.8% for second−/later‐line). Median (95% CI) progression‐free survival (PFS) was 13.7 (11.6–17.0) months. For first‐line recipients, overall survival (OS) was 26.3 (17.6–35.0) months. No significant difference in ORR, PFS and OS, according to the setting of crizotinib initiation, was observed. In a multivariate Cox regression analysis, old age, male gender, initially metastatic, and number of metastatic organs were associated with poor PFS and OS. The most common adverse events were nausea and vomiting, and severe adverse event leading to dose adjustment was hepatotoxicity. Conclusions ORR, PFS, OS, and adverse event profiles were comparable to previous clinical trials. Our findings could aid in the efficient management of ALK‐positive lung cancer patients.

Background Among the various diaphragm-sparing alternatives to interscalene block, costoclavicular block (CCB) demonstrated a low hemidiaphragmatic paresis (HDP) occurrence but an inconsistent analgesic effect in arthroscopic shoulder surgery. We hypothesized that a larger volume of local anesthetic for CCB could provide sufficient analgesia by achieving sufficient supraclavicular spreading. Methods Sixty patients scheduled for arthroscopic rotator cuff repair were randomly assigned to receive CCB using one of two volumes of local anesthetic (CCB20, 0.75% ropivacaine 20 ml; CCB40, 0.375% ropivacaine 40 ml). The primary outcome was the rate of complete analgesia (0 on the numeric rating scale of pain) at 1 h postoperatively. The secondary outcomes included a sonographic assessment of local anesthetic spread, diaphragmatic function, pulmonary function, postoperative opioid use, and other pain-related experiences within 24 h postoperatively. Results The rates of complete analgesia were not significantly different (23.3% [7/30] and 33.3% [10/30] in the CCB20 and CCB40 groups, respectively; risk difference 10%, 95% CI [–13, 32], P = 0.567). There were no significant differences in other pain-related outcomes. Among the clinical factors considered, the only factor significantly associated with postoperative pain was the sonographic observation of supraclavicular spreading. There were no significant differences in the incidence of HDP and the change in pulmonary function between the two groups. Conclusions Using 40 ml of local anesthetic does not guarantee supraclavicular spread during CCB. Moreover, it does not result in a higher rate of complete analgesia compared to using 20 ml of local anesthetic in arthroscopic shoulder surgery.

Abstract Background It is unknown whether high hemoglobin A1c (HbA1c) is associated with increases in the risk of cardiovascular disease among individuals with elevated genetic susceptibility. We aimed to investigate the association between HbA1c and atrial fibrillation (AF), coronary artery disease (CAD), and ischemic stroke according to the polygenic risk score (PRS). Methods The UK Biobank cohort included 502,442 participants aged 40–70 years who were recruited from 22 assessment centers across the United Kingdom from 2006 to 2010. This study included 305,605 unrelated individuals with available PRS and assessed new-onset AF, CAD, and ischemic stroke. The participants were divided into tertiles based on the validated PRS for each outcome. Within each PRS tertiles, the risks of incident events associated with HbA1c levels were investigated and compared with HbA1c

Abstract Background Petersen’s hernia, which occurs after Billroth-II (B-II) or Roux-en-Y (REY) anastomosis, can be reduced by defect closure. This study aims to compare the incidence of bowel obstruction above Clavien–Dindo classification grade III due to Petersen’s hernia between the mesenteric fixation method and the conventional methods after laparoscopic or robotic gastrectomy. Methods This study was designed as prospective, single-blind, non-inferiority randomized controlled multicenter trial in Korea. Patients with histologically diagnosed gastric cancer of clinical stages I, II, or III who underwent B-II or REY anastomosis after laparoscopic or robotic gastrectomy are enrolled in this study. Participants who meet the inclusion criteria are randomly assigned to two groups: a CLOSURE group that underwent conventional Petersen’s defect closure method and a MEFIX group that underwent the mesenteric fixation method. The primary endpoint is the number of patients who underwent surgery for bowel obstruction caused by Petersen’s hernia within 3 years after laparoscopic or robotic gastrectomy. Discussion This trial is expected to provide high-level evidence showing that the MEFIX method can quickly and easily close Petersen’s defect without increased postoperative complications compared to the conventional method. Trial registration ClinicalTrials.gov NCT05105360. Registered on November 3, 2021.

Abstract Background Glioblastoma (GBM) is more difficult to treat than other intractable adult tumors. The main reason that GBM is so difficult to treat is that it is highly infiltrative. Migrasomes are newly discovered membrane structures observed in migrating cells. Thus, they can be generated from GBM cells that have the ability to migrate along the brain parenchyma. However, the function of migrasomes has not yet been elucidated in GBM cells. Results Here, we describe the composition and function of migrasomes generated along with GBM cell migration. Proteomic analysis revealed that LC3B-positive autophagosomes were abundant in the migrasomes of GBM cells. An increased number of migrasomes was observed following treatment with chloroquine (CQ) or inhibition of the expression of STX17 and SNAP29, which are involved in autophagosome/lysosome fusion. Furthermore, depletion of ITGA5 or TSPAN4 did not relieve endoplasmic reticulum (ER) stress in cells, resulting in cell death. Conclusions Taken together, our study suggests that increasing the number of autophagosomes, through inhibition of autophagosome/lysosome fusion, generates migrasomes that have the capacity to alleviate cellular stress.

Abstract Distributed quantum metrology has drawn intense interest as it outperforms the optimal classical counterparts in estimating multiple distributed parameters. However, most schemes so far have required entangled resources consisting of photon numbers equal to or more than the parameter numbers, which is a fairly demanding requirement as the number of nodes increases. Here, we present a distributed quantum sensing scenario in which quantum-enhanced sensitivity can be achieved with fewer photons than the number of parameters. As an experimental demonstration, using a two-photon entangled state, we estimate four phases distributed 3 km away from the central node, resulting in a 2.2 dB sensitivity enhancement from the standard quantum limit. Our results show that the Heisenberg scaling can be achieved even when using fewer photons than the number of parameters. We believe our scheme will open a pathway to perform large-scale distributed quantum sensing with currently available entangled sources.

Purpose: There is increasing interest in the use of ultrasound for endoscopic and percutaneous procedures. Access can be achieved without radiation exposure under ultrasound guidance. Our aim was to develop a porcine-based training model for ultrasound-guided percutaneous renal access that could also be personalized to a specific patient. Materials and Methods: The Institutional Animal Care and Use Committee of Severance Hospital approved the study protocol. An anesthetized pig was placed in the dorsal lithotomy position. For the nephrostomy puncture, a Chiba biopsy needle with an echo tip was used under ultrasound guidance. Eight residents and three consultants in urology participated. Puncture time was defined as the nephrostomy time to confirm the flow of irrigation via the needle. After training, satisfaction survey results for clinical usability and procedural difficulty were evaluated. Results: The 5-point Likert scale satisfaction survey for clinical usability and procedural difficulty found mean results of 4.64 and 4.09 points, respectively. There were no differences between residents and consultants for either variable. For all participants combined, there was a significant difference for nephrostomy time between the first and second trials (278.8±70.6 s vs. 244.5±47.0 s; p=0.007). The between-trial difference was greater for residents (291.5±71.2 s vs. 259.1±41.9 s; p=0.039). The difference for the consultant was not significant (245.0±69.4 s vs. 205.7±42.5 s; p=0.250). Conclusions: We developed a porcine-based ultrasound-guided nephrostomy puncture training model. Satisfaction survey results indicated high clinical usability and procedural difficulty. For nephrostomy time, the model was more effective for urology residents than for consultants.

Exhausting carbon-based gases from building construction or comfortable household supplies have caused the main pollution gas species for the indoor air environment. Given the variety of indoor activities, many reports have been challenged to find room-temperature operational and harmless materials. Here, we report that the activating MoO vibration mode in Na,Sb doped-NiMoO4 micro-sized powder reveals the high response of CO and VOC, occupying multiple bonds at room temperature. We performed Na and Sb doping in the α-NiMoO4 crystal structure, such as introducing the Sb in Ni and interstitial doping of Na in around 4 Å of free space in the NiMoO4 crystal structure that manipulates the partial β-NiMoO4 phase. The Na,Sb-codoped NiMoO4 generates the higher MoO vibration mode from FT-IR measurement and enables carbon-based gas detection with 38 responses to CO and nearly 20 responses to VOC under 20 ppm of each analyte gases environment. Furthermore, the n-type gas sensing behavior of Na,Sb doped-NiMoO4 chemiresistor exhibits an immediate sensing response instead of a none-of response than intrinsic or single element doped NiMoO4. These results suggest that Na,Sb codoped-NiMoO4 is the applicable material for emergent warning against carbon-based gas exposure in the indoor environment. In addition, activating the electrochemical reaction site of MoO4–2 in NiMoO4 is tailorable by a simple doping process.

Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV) infection, continues to pose significant public health challenges worldwide despite efficient vaccines. The virus is classified into five genotypes, among which genotype V (GV) was not detected for a long period after its initial isolation in 1952, until reports emerged from China and the Republic of Korea (ROK) since 2009. The characteristics of the virus are crucial in estimating its potential epidemiological impact. However, characterization of GV JEVs has so far been limited to two strains: Muar, the original isolate, and XZ0934, isolated in China. Two additional ROK GV JEV isolates, NCCP 43279 and NCCP 43413, are currently available, but their characteristics have not been explored. Our phylogenetic analysis revealed that GV virus sequences from the ROK segregate into two clades. NCCP 43279 and NCCP 43413 belong to different clades and exhibit distinct in vitro phenotypes. NCCP 43279 forms larger plaques but demonstrates inefficient propagation in cell culture compared to NCCP 43413. In vivo, NCCP 43279 induces higher morbidity and mortality in mice than NCCP 43413. Notably, NCCP 43279 shows more severe blood–brain barrier damage, suggesting superior brain invasion capabilities. Consistent with its higher virulence, NCCP 43279 displays more pronounced histopathological and immunopathological outcomes. In conclusion, our study confirms that the two ROK isolates are not only classified into different clades but also exhibit distinct in vitro and in vivo characteristics.

Microplastic (MP) contamination has become a pervasive global issue, affecting terrestrial and aquatic environments, and its potential health hazards are of widespread concern. This review examined the intricate relationship between animal exposure to MPs and their health effects, revealing that MP contamination affects a broad spectrum of animal species across terrestrial and aquatic habitats. Crucially, interspecies differences in ingestion, accumulation, and responses to MPs emerge as central themes arising from various factors, including feeding behavior, physiology, and ecological niches. The health implications of MP exposure are multifarious; animals may suffer physical harm, endure chemical exposure to adsorbed contaminants, provoke inflammatory responses, and undergo behavioral modifications. Chronic exposure to MPs raises concerns about their long-term health consequences, and the ability of MPs to adsorb and transport chemicals has implications for the bioaccumulation of pollutants within food webs. The ecological ramifications of MP contamination are profound, impacting animal behavior, population dynamics, and ecosystem processes. The intricate interplay between animals and MPs underscores the need for interdisciplinary research that unites fields such as biology, ecology, chemistry, and toxicology. Recognizing the relationship between animal exposure to MPs and their health effects has significant implications, particularly as the potential for MPs to enter the human food chain through animals underscores the need for research on human health risks.