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Abstract Recent information regarding the characteristics of people living with human immunodeficiency virus (HIV) (PLWH) is lacking. Therefore, we examined the incidence of HIV infection and epidemiologic characteristics of PLWH in South Korea using recent National Health Insurance Service database data. The HIV infection rate was 4.13 per 100,000 in 2017, 4.19 per 100,000 in 2018, 6.61 per 100,000 in 2019, 5.98 per 100,000 in 2020, 8.81 per 100,000 in 2021, and 4.14 per 100,000 in 2022. In 2016, the mean age of PLWH was 45.7 years (SD: 13.8 years), and it gradually increased to 49.0 years (standard deviation: 13.7 years) in 2022 over 7 years in South Korea. The proportion of male individuals among PLWH was 90.7% (19,970/22,026) in 2016, and it gradually increased to 92.3% (22,943/24,857) in 2022 over 7 years in South Korea. The proportion of anti-retroviral therapy (ART) users among PLWH in South Korea was 92.6% (20,388/22,026) in 2016, and it gradually increased to 97.9% (24,328/24,857) in 2022 over 7 years. In this population-based cohort analysis, we presented the HIV infection incidence and epidemiologic features of PLWH in South Korea. This study’s results may influence future infection prevention strategies and policies for PLWH.

This study was to investigate effects of different phytogenic feed additives (PFA) in grower finishing pigs with stressed by high stocking density. A total of 84 growing pigs ([Landrace × Yorkshire] × Duroc) with initial body weight (BW) of 28.23 ± 0.21 kg were used for 10 weeks (4 replicate pens with 3 pigs per pen). The dietary treatment consisted of basal diets in animal welfare density (positive control [PC]), basal diet in high stocking density (negative control [NC]), NC + 0.04% bitter citrus extract (PT1), NC + 0.01% microencapsulated blend of thymol & carvacrol (PT2), NC + 0.10% mixture of 40% bitter citrus extract and 10% microencapsulated blend of thymol and carvacrol (PT3), NC + 0.04% premixture of grape seed and grape marc extract, green tea and hops (PT4), and NC + 0.10% fenugreek seed powder (PT5). The reduction of space allowance significantly decreased (p < 0.05) growth performance (average daily gain, average daily feed intake, feed efficiency) and nutrient digestibility (dry matter, crude protein). Also, the fecal score of NC group increased (p < 0.05) compared with other groups. In blood profiles, lymphocyte decreased (p < 0.05), and neutrophil, cortisol, TNF-α increased (p < 0.05) when pigs were in high stocking density. Basic behaviors (feed intake, standing, lying) were inactive (p < 0.05) and singularity behavior (biting) were increased (p < 0.05) under high stocking density. However, PFA groups alleviated the negative effects such as reducing growth performance, nutrient digestibility, increasing stress indicators in blood and animal behavior. In conclusion, PFA groups improved the health of pigs with stressed by high stocking density and PT3 is the most effective.

Abstract Limited evidence exists regarding the link between coronavirus disease 2019 (COVID-19) and pneumothorax. Therefore, we aimed to evaluate the occurrence rate of pneumothorax in hospitalized patients with COVID-19 and compare the risk of pneumothorax between patients with COVID-19 and influenza. This retrospective cohort study used patient data from the National Health Insurance Service of South Korea. Patients diagnosed with COVID-19 (December 2019 to December 2021) and influenza (January 2019 to December 2021) who required hospitalization and respiratory support were included. We identified 46,460 patients with COVID-19 and 6,117 with influenza. The occurrence rate of pneumothorax was 0.74% in patients with COVID-19. In an inverse probability of treatment weighting matched cohort, the Cox proportional hazards regression model showed that COVID-19 was not associated with an increased risk of pneumothorax compared to influenza (hazard ratio, 1.22; 95% confidence interval, 0.75–1.99). However, the risk of pneumothorax associated with COVID-19 compared to influenza was significantly higher in patients without chronic lung disease than in those with (P for heterogeneity = 0.037). In conclusion, COVID-19, compared with influenza, is not associated with an increased risk of pneumothorax; however, it is associated with an increased risk in patients without chronic lung disease.

Peucedanum L. (Apiaceae) is broadly distributed in the Old World, and 11 taxa, including five endemic species, have been reported in Korea. In this study, we used scanning electron microscopy to describe petal epidermal cell patterns and evaluated their systematic implications for all Korean Peucedanum species except for one. This included two recently reported endemic species, P. miroense and P. tongkangense, which are closely associated with Heracleum moellendorffii. The epidermal characteristics of the petals, including cell type (papillose conical, papillose knobby rugose, tabular conical, or tabular rugose), anticlinal wall shape (straight, sinuous, or curved), cuticle sculpture (striate or wrinkled), and stomata (presence or absence) were observed. The petal epidermis could be categorized into three types and two subtypes. We concluded that petal epidermal characteristics provide evidence supporting the recent robust phylogeny that suggests the non-monophyly of the genus Peucedanum. In particular, P. japonicum and P. praeruptorum, which are positioned in different clades to the other species in the recent phylogeny, had different types of petal epidermis among the studied species. These petal epidermal micro-characteristics were evaluated as possible consistent parameters for the taxonomic delimitation of species of the genus Peucedanum.

Objective Upadacitinib improved the signs and symptoms of non‐radiographic axial spondyloarthritis (nr‐axSpA) versus placebo over 14 weeks in the primary analysis of the SELECT‐AXIS 2 nr‐axSpA study. Here, we evaluated the efficacy and safety of upadacitinib through 1 year in patients with nr‐axSpA in SELECT‐AXIS 2. Methods Patients aged at least 18 years diagnosed with nr‐axSpA who fulfilled the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria and were receiving stable background therapy were randomized to upadacitinib 15 mg once daily or placebo for the 52‐week double‐blind period. Efficacy was assessed using non‐responder imputation incorporating multiple imputation (NRI‐MI) and as‐observed analyses for binary endpoints, and mixed‐effects model repeated measures for continuous endpoints. Results Of 314 randomized patients, 259 (upadacitinib, n = 129; placebo, n = 130) completed 52 weeks of treatment. More patients receiving upadacitinib versus placebo achieved ≥40% improvement in ASAS at week 52 (63% vs 43%, NRI‐MI; nominal P < 0.001). Similar treatment effects were observed for the achievement of axSpA Disease Activity Score inactive disease (33% v 11%, NRI‐MI; nominal P < 0.001). Overall, patients receiving upadacitinib versus placebo showed greater improvement in disease activity, inflammation, pain, function, enthesitis, and quality of life through 52 weeks. Adverse events were generally comparable between the treatment groups. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, inflammatory bowel disease, or deaths were reported in those receiving upadacitinib. Conclusion Treatment with upadacitinib showed sustained efficacy versus placebo with no new safety findings identified through 1 year. These results support the continued favorable benefit–risk profile of upadacitinib treatment for nr‐axSpA.

Abstract Background Despite the frequent diagnostic delays of rare neurologic diseases (RND), it remains difficult to study RNDs and their comorbidities due to their rarity and hence the statistical underpowering. Affecting one to two in a million annually, stiff person syndrome (SPS) is an RND characterized by painful muscle spasms and rigidity. Leveraging underutilized electronic health records (EHR), this study showcased a machine-learning-based framework to identify clinical features that optimally characterize the diagnosis of SPS. Methods A machine-learning-based feature selection approach was employed on 319 items from the past medical histories of 48 individuals (23 with a diagnosis of SPS and 25 controls) with elevated serum autoantibodies against glutamic-acid-decarboxylase-65 (anti-GAD65) in Dartmouth Health’s EHR to determine features with the highest discriminatory power. Each iteration of the algorithm implemented a Support Vector Machine (SVM) model, generating importance scores—SHapley Additive exPlanation (SHAP) values—for each feature and removing one with the least salient. Evaluation metrics were calculated through repeated stratified cross-validation. Results Depression, hypothyroidism, GERD, and joint pain were the most characteristic features of SPS. Utilizing these features, the SVM model attained precision of 0.817 (95% CI 0.795–0.840), sensitivity of 0.766 (95% CI 0.743–0.790), F-score of 0.761 (95% CI 0.744–0.778), AUC of 0.808 (95% CI 0.791–0.825), and accuracy of 0.775 (95% CI 0.759–0.790). Conclusions This framework discerned features that, with further research, may help fully characterize the pathologic mechanism of SPS: depression, hypothyroidism, and GERD may respectively represent comorbidities through common inflammatory, genetic, and dysautonomic links. This methodology could address diagnostic challenges in neurology by uncovering latent associations and generating hypotheses for RNDs.

Background It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and 100 and

Abstract Background Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. Methods This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. Results We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21–63). There was a significant inverse correlation between age and Sab levels after the second dose (slope − 14.96, P = 0.032), and this was more pronounced after the third dose (slope − 208.9, P

Abstract Microbubbles (MBs) combined with focused ultrasound (FUS) has emerged as a promising noninvasive technique to permeabilize the blood–brain barrier (BBB) for drug delivery into the brain. However, the safety and biological consequences of BBB opening (BBBO) remain incompletely understood. This study aims to investigate the effects of two parameters mediating BBBO: microbubble volume dose (MVD) and mechanical index (MI). High-resolution MRI-guided FUS was employed in mouse brains to assess BBBO by manipulating these two parameters. Afterward, the sterile inflammatory response (SIR) was studied 6 h post-FUS treatment. Results demonstrated that both MVD and MI significantly influenced the extent of BBBO, with higher MVD and MI leading to increased permeability. Moreover, RNA sequencing revealed upregulation of major inflammatory pathways and immune cell infiltration after BBBO, indicating the presence and extent of SIR. Gene set enrichment analysis identified 12 gene sets associated with inflammatory responses that were significantly upregulated at higher MVD or MI. A therapeutic window was established between therapeutically relevant BBBO and the onset of SIR, providing operating regimes to avoid damage from stimulation of the NFκB pathway via TNFɑ signaling to apoptosis. These results contribute to the optimization and standardization of BBB opening parameters for safe and effective drug delivery to the brain and further elucidate the underlying molecular mechanisms driving sterile inflammation.

Abstract Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients’ blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients’ clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

Abstract Age-related macular degeneration (AMD) is one of the major causes of blindness in the elderly worldwide. Anti-vascular endothelial growth factor (VEGF) drugs have been widely used to treat the neovascular type of AMD (nAMD). However, VEGF acts not only as a pro-angiogenic factor but also as an anti-apoptotic factor in the eyes. In this study, we found that anti-VEGF drugs, including bevacizumab (Bev), ranibizumab (Ran), and aflibercept (Afl), induced epithelial-mesenchymal transition (EMT) in ARPE-19 cells in vitro, accompanied by the induction of CCN2, a potent pro-fibrotic factor. Similarly, intravitreal injection of Afl into mouse eyes resulted in EMT in the retinal pigmented epithelium (RPE). Co-treatment with CCN5, an anti-fibrotic factor that down-regulates CCN2 expression, significantly attenuated the adverse effects of the anti-VEGF drugs both in vitro and in vivo. Inhibition of the VEGF signaling pathway with antagonists of VEGF receptors, SU5416 and ZM323881, induced EMT and up-regulated CCN2 in ARPE-19 cells. Additionally, knock-down of CCN2 with siRNA abolished the adverse effects of the anti-VEGF drugs in ARPE-19 cells. Collectively, these results suggest that anti-VEGF drugs induce EMT in RPE through the induction of CCN2 and that co-treatment with CCN5 attenuates the adverse effects of anti-VEGF drugs in mouse eyes.

Abstract We propose a minimal extension of the Standard Model with the Peccei-Quinn (PQ) scalar field and explain the relic density of the QCD axion through the kinetic misalignment with a relatively small axion decay constant. To this purpose, we consider a slow-roll inflation from the radial component of the PQ field with the PQ conserving potential near the pole of its kinetic term and investigate the post-inflationary dynamics of the PQ field for reheating. The angular mode of the PQ field, identified with the QCD axion, receives a nonzero velocity during inflation due to the PQ violating potential, evolving with an approximately conserved Noether PQ charge. We determine the reheating temperature from the perturbative decays and scattering processes of the inflaton and obtain dark radiation from the axions produced from the inflaton scattering at a testable level in the future Cosmic Microwave Background experiments. We show the correlation between the reheating temperature, the initial velocity of the axion and the axion decay constant, realizing the axion kinetic misalignment for the correct relic density.

Purpose The Korean Society of Coloproctology has been conducting Colorectal Cancer Awareness Campaign, also known as the Gold Ribbon Campaign, every September since 2007. The 2022 campaign was held through a metaverse platform targeting the younger age group under the slogan of raising awareness of early-onset colorectal cancer (CRC). This study aimed to analyze the impact of the 2022 campaign on a metaverse platform. Methods Anonymized survey data were collected from participants in the metaverse campaign from September 1 to 15, 2022. The satisfaction score of the participants was evaluated by sex, age group, and previous campaign participation status. Results During the campaign, 2,770 people visited the metaverse. Among them, 455 people participated in the survey (response rate, 16.4%). Approximately 95% of the participants reported being satisfied with the information provided by the campaign, understood the necessity of undergoing screening for and prevention of early-onset CRC, and were familiar with the structure of the metaverse. The satisfaction score for campaign information tended to decrease as the participants’ age increased. When the participants’ overall level of satisfaction with the metaverse platform was assessed, teenagers scored particularly lower than the other age groups. The satisfaction scores for CRC information provided in the metaverse, as well as the scores for recognizing the seriousness and necessity of screening for early-onset CRC, indicated a high positive tendency (P

In a survey conducted in March 2023, Euphorbia hypogaea plants cultivated within greenhouses in Yongin, Korea exhibited water-soaked areas near the stem base, close to the soil. Subsequent isolation from diseased E. hypogaea led to the identification of a bacterial strain, designated as CBNUMPBL-103. The isolate was identified as Dickeya dadantii through sequencing of the 16s rRNA and phylogenetic analysis. The pathogenicity of the isolate was confirmed by inoculating it into healthy E. hypogaea, resulting in the manifestation of similar symptoms observed during the survey. The re-isolated strain recovered from inoculated plants showed a similar morphology with the inoculated strain. This is the first documentation of D. dadantii causing soft rot of E. hypogaea in Korea.

Abstract Constipation is a highly prevalent gastrointestinal disorder in patients with chronic kidney disease (CKD). However, our understanding of its epidemiology and management in CKD is limited. We aimed to explore real-world data on constipation and laxative use in patients with CKD in a nationwide population-based cohort from the Korean Health Insurance Review and Assessment-National Patient Sample database. This study analyzed retrospective health claims data in Korea from 2012 to 2017 that were transformed into the Observational Medical Outcomes Partnership Common Data Model. The pooled proportion of constipation diagnoses was 30.5% in all patients with CKD and 15.9%, 16.5%, 17.4%, 29.9%, and 43.3% in patients with CKD stages 1–5, respectively, suggesting a higher prevalence in advanced CKD. Patients receiving peritoneal dialysis or hemodialysis had the highest prevalence of constipation, while transplant recipients showed a prevalence comparable to that of patients with early CKD. Patients with CKD had a significantly higher risk of constipation than age- and sex-matched non-CKD individuals (range of odds ratio [OR]:1.66–1.90). Laxative prescribing patterns differed by CKD severity. Osmotic agents were prescribed in more than half of patients with advanced CKD, while magnesium salts and bulking agents were prescribed less frequently. The CKD patients with constipation were more likely to be prescribed constipation-inducing medications, including antipsychotic and neurological medications. Our findings provide real-world constipation and laxative prescription status in the Korean CKD population, revealing a significantly higher risk of constipation and different laxative prescribing patterns in patients with CKD.

In this article, compensation algorithms for zero padding are suggested to enhance the performance of deep convolutional neural networks. By considering the characteristics of convolving filters, the proposed methods efficiently compensate convolutional output errors due to zero padded inputs in a convolutional neural network. Primarily the algorithms are developed for patch based SRResNet for Single Image Super Resolution and the performance comparison is carried out using the SRResNet model but due to generalized nature of the padding algorithms its efficacy is tested in U-Net for Lung CT Image Segmentation. The proposed algorithms show better performance than the existing algorithm called partial convolution based padding (PCP), developed recently.

A 5-year-old neutered female Korean domestic shorthair cat diagnosed with oral squamous cell carcinoma (SCC) presented to the hospital with severe oral purulent discharge, anorexia, and lethargy. Owing to extensive lesions, surgical excision and radiation therapy were not feasible. Instead, prior to metronomic therapy with toceranib, the patient received an intravenous injection of feline umbilical cord-derived mesenchymal stem cells (fUC-MSCs) (1 × 106 cells/10 mL of saline) to reduce inflammation. No acute side effects (such as fever, increased respiratory rate, diarrhea, and vomiting) were observed following stem cell therapy. For 6 days, purulent discharge, bleeding, swelling, a bad odor, and crust exfoliation in the tumor area on the face were dramatically reduced. However, the patient exhibited difficulty in voluntarily receiving foods, and weight loss persisted. Starting from the 7th day, purulent discharge, bleeding, and odor at the SCC area worsened again. Toceranib, low-dose NSAIDs (meloxicam, every other day), antibiotics (cefazoline), and gabapentin were administered; however, they were not effective in reducing the pus, bleeding, foul odor, and crust exfoliation at the SCC area. Symptoms of pain, weakness, and weight loss progressed, leading to the choice of euthanasia with the owner’s consent approximately 1 month later. This case report reveals that allogeneic fUC-MSCs have a slight short-term effect on purulent discharge, bleeding, odor, and crust exfoliation and may be additional therapy for feline oral SCC.

BackgroundThe liver fluke Clonorchis sinensis imports large amounts of glucose to generate energy and metabolic intermediates through glycolysis. We hypothesized that C. sinensis absorbs glucose through glucose transporters and identified four subtypes of glucose transporter (CsGTP) and one sodium glucose co-transporter (CsSGLT) in C. sinensis.Methodology/principal findingsExpressed sequence tags encoding CsGTPs were retrieved from the C. sinensis transcriptome database, and their full-length cDNA sequences were obtained by rapid amplification of cDNA ends (RACE). The tissue distribution of glucose transporters in C. sinensis adults was determined using immunohistochemical staining. Developmental expression was measured using RT-qPCR. The transport and distribution of glucose into living C. sinensis were monitored using confocal microscopy. Membrane topology and key functional residues of CsGTPs were homologous to their counterparts in animals and humans. CsGTP1, 2, and 4 were transcribed 2.4-5.5 times higher in the adults than metacercariae, while CsGTP3 was transcribed 2.1 times higher in the metacercariae than adults. CsSGLT transcription was 163.6 times higher in adults than in metacercariae. In adults, CsSGLT was most abundant in the tegument; CsGTP3 and CsSGLT were localized in the vitelline gland, uterine wall, eggs, mesenchymal tissue, and testes; CsGTP4 was found in sperm and mesenchymal tissue; and CsGTP1 was mainly in the sperm and testes. In C. sinensis adults, exogenous glucose is imported in a short time and is present mainly in the middle and posterior body, in which the somatic and reproductive organs are located. Of the exogenous glucose, 53.6% was imported through CsSGLT and 46.4% through CsGTPs. Exogenous glucose import was effectively inhibited by cytochalasin B and phlorizin.Conclusions/significanceWe propose that CsSGLT cooperates with CsGTPs to import exogenous glucose from the environmental bile, transport glucose across mesenchymal tissue cells, and finally supply energy-demanding organs in C. sinensis adults. Studies on glucose transporters may pave the way for the development of new anthelmintic drugs.

Introduction: Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of regional chemotherapy using paclitaxel, albumin-paclitaxel, and liposome-encapsulated albumin-paclitaxel via subserosal injection in rat models employing nuclear medicine and molecular imaging technology.Method: Nine Sprague Dawley rats were divided into three groups: paclitaxel (n = 3), albumin-paclitaxel nano-particles (APNs; n = 3), and liposome-encapsulated APNs (n = 3). [123I]Iodo-paclitaxel ([123I]I-paclitaxel) was synthesized by conventional electrophilic radioiodination using tert-butylstannyl substituted paclitaxel as the precursor. Albumin-[123I]iodo-paclitaxel nanoparticles ([123I]APNs) were prepared using a desolvation technique. Liposome-encapsulated APNs (L-[123I]APNs) were prepared by thin-film hydration using DSPE-PEG2000, HSPC, and cholesterol. The rats in each group were injected with each test drug into the subserosa of the stomach antrum. After predetermined times (30 min, 2, 4, 8 h, and 24 h), molecular images of nuclear medicine were acquired using single-photon emission computed tomography/computed tomography.Results: Paclitaxel, APNs, and L-APNs showed a high cumulative distribution in the stomach, with L-APNs showing the largest area under the curve. Most drugs administered via the gastric subserosal route are distributed in the stomach and intestines, with a low uptake of less than 1% in other major organs. The time to reach the maximum concentration in the intestine for L-APNs, paclitaxel, and APNs was 6.67, 5.33, and 4.00 h, respectively.Conclusion: These preliminary results imply that L-APNs have the potential to serve as a novel paclitaxel preparation method for the regional treatment of gastric cancer.

Recent studies actively researching user identification utilizing physiological information to verify identity. However, there is a problem with biometric information exposed to the outside of the body being susceptible to forgery and falsification. Therefore, studies on user identification systems based on biometric signals generated as electrical signals inside the body are necessary to strengthen security with high security and continuous authentication. Among the time-frequency (TF) features applied to existing nonlinear biosignals, short-time fourier transform (STFT) cannot simultaneously improve time-frequency resolution, so there is a limit to improving user identification accuracy. Therefore, this paper introduces a customized constant q transform (CQT) for time-frequency resolution adjustment applied to multiple biosignals. Additionally, a multi-stream conformer combining a convolutional neural network (CNN) and transformer is employed to improve user identification accuracy. Test results confirmed that when using CQT features and a multi-stream conformer for electrocardiogram (ECG) and electroencephalogram (EEG) signals, the accuracy of user identification using both ECG and EEG signals was 97.6%, an improvement of 0.8% or more compared to the accuracy of ECG and EEG single biosignals and CNN-based user identification.

Abstract Galactomannan (GM) is a polysaccharide cell wall component released by Aspergillus spp., and an immunoenzymatic GM assay is used for the diagnosis of invasive pulmonary aspergillosis. We evaluated the cause of strong positivity for GM in patients with no typical signs of aspergillosis. Repeat assays were performed using different instruments and reagent lots, but there were no differences in results among the assays. Patients with strongly positive GM results were investigated. Medication histories revealed that 14 of 23 patients had been administered total parenteral nutrition solution from one manufacturer and 4 patients had been administered dextrose solution from a different manufacturer before being tested. The results of GM assays conducted on samples of dextrose solution and the glucose fraction of the total parenteral nutrition solution were strongly positive, confirming the causes of the false-positive reactions. We hypothesize that a trace amount of GM was introduced into the glucose-containing solutions because glucoamylase, which is necessary for the saccharification step of glucose synthesis, was derived from Aspergillus niger. To enhance patient care and prevent unnecessary antifungal prescriptions, healthcare providers and manufacturers of healthcare products need to be aware of the possibility of false-positive reactions for GM.

This paper proposes a 500 MS/s 4-bit flash analog-to-digital converter (ADC) featuring a differential input voltage range of 1.2 Vpp operating at a supply voltage of 1.2 V. Although the proposed circuit utilizes a conventional flash ADC structure, its track and hold circuit, driving buffer, and preamp circuits corresponding to the analog stages are designed using complementary architecture to attain a sufficient swing range even at a low supply voltage. Notably, the proposed structure satisfies the error requirements. The error source of the flash ADC, such as the comparator’s input referred offset, did not degrade its performance, while the use of a calibration circuit, characterized by power consumption and area burdens and increased complexity, could also be avoided. Therefore, the proposed flash ADC met the error requirements, such as the comparator’s input referred offset, without the need for calibration circuits. The chip, fabricated using the TSMC 65 nm process, covers an area of 1,160 × 950 μm2 and consumes 78 mW of power. Furthermore, its signal-to-noise and distortion ratio and spurious-free dynamic range were measured to be 23.36 dB and 30.26 dB, respectively, at a sampling frequency of 500 MHz.

In the information age, people are increasingly being exposed to stress as societies are experiencing sudden changes fueled by advancements in cutting-edge scientific technology and the Information Technology (IT) industry. Consequently, research has been actively conducted on stress classification to mitigate psychological and physical diseases caused by constantly feeling stressed. Specifically, the number of studies examining electrocardiograms (ECGs), which record biosignals that provide insight into the response level of the body’s autonomic nervous system, has increased. However, previous studies on stress classification based on ECG used only one-dimensional feature data, thus entailing difficulties in analyzing the data more closely and comprehensively owing to bias toward a specific aspect. Therefore, to overcome the limitations of conventional stress classification based on ECGs, this paper developed a stress classification method based on multi-dimensional feature fusion of LSTM and Xception using ECGs from which outliers have been removed. Experimental results showed that applying multi-dimensional feature fusion of the weighted average method using ECG data with outlier signals removed resulted in a stress classification of 99.51%, a 1.25% improvement from previous studies which used only one-dimensional feature data of ECGs, thus highlighting the excellent performance of the proposed stress classification method using ECGs based on multi-dimensional feature fusion of LSTM and Xception.

Allium is a complicated genus that includes approximately 1000 species. Although its morphology is well studied, the taxonomic importance of many morphological traits, including floral traits, are poorly understood. Here, we examined and measured the floral characteristics of 87 accessions of 74 Allium taxa (belonging to 30 sections and nine subgenera) from Central to Eastern Asian countries. We then examined the taxonomic relationships between select flower characteristics and a phylogenetic tree based on ITS sequences. Our results confirm that floral morphology provides key taxonomic information to assess species delimitation in Allium. We found that perianth color is an important characteristic within the subg. Melanocrommyum, Polyprason, and Reticulatobulbosa. In subg. Allium, Cepa, and Rhizirideum, significant characteristics include ovary shape, perianth shape, and inner tepal apex. For species in subg. Angunium, the key taxonomic character is ovule number (only one ovule in per locule). In the subg. Allium, Cepa, Polyprason, and Reticulatobulbosa, which belong to the third evolutionary line of Allium, hood-like appendages occur in the ovary, although these do not occur in subg. Rhizirideum. Our results also indicated that the flower morphology of several species in some sections are not clearly distinguished, e.g., sect. Sacculiferum (subg. Cepa) and sect. Tenuissima (subg. Rhizirideum). This study provides detailed photographs and descriptions of floral characteristics and information on general distributions, habitats, and phenology of the studied taxa.

Abstract Major Depressive Disorder (MDD) presents considerable challenges to diagnosis and management due to symptom variability across time. Only recent work has highlighted the clinical implications for interrogating depression symptom variability. Thus, the present work investigates how sociodemographic, comorbidity, movement, and sleep data is associated with long-term depression symptom variability. Participant information included (N = 939) baseline sociodemographic and comorbidity data, longitudinal, passively collected wearable data, and Patient Health Questionnaire-9 (PHQ-9) scores collected over 12 months. An ensemble machine learning approach was used to detect long-term depression symptom variability via: (i) a domain-driven feature selection approach and (ii) an exhaustive feature-inclusion approach. SHapley Additive exPlanations (SHAP) were used to interrogate variable importance and directionality. The composite domain-driven and exhaustive inclusion models were both capable of moderately detecting long-term depression symptom variability (r = 0.33 and r = 0.39, respectively). Our results indicate the incremental predictive validity of sociodemographic, comorbidity, and passively collected wearable movement and sleep data in detecting long-term depression symptom variability.

In this study, the characteristics of ammonia and their effects on secondary particulate matter (PM) formation were analyzed by region in Korea in 2020. The NH3 concentration was high in GJ (11.4 ppb), a neighboring agricultural area, followed by DJ (9.0 ppb) and SE (8.6 ppb), which are located in urban areas. On the other hand, BI (2.6 ppb) and JI (4.5 ppb), which are background regions, demonstrated a lower concentration than other areas. Seasonally, ammonia was high in spring and summer, and it generally increased when human activities are active. Therefore, it is believed that the ammonia in the atmosphere not only changes depending on local emissions, but also based on temperature-dependent phase distribution characteristics. For SE and GJ, regions with relatively high ammonia concentrations, investigations into the effect of ammonia on secondary PM formation were conducted. In both regions, the ammonium-to-sulfate mole ratio tended to increase with increasing ammonia or PM2.5 concentration. It can be assumed that the PM2.5 concentration increases as nitrates are formed under the ammonia-sufficient condition. The adjusted gas ratio is generally greater than 4, indicating that there is a lot of free ammonia. Thus, it is estimated that a reduction in ammonia would not be effective to restrain nitrate formation.

This study investigated the effects of ascochlorin (ASC), a natural compound derived from the fungus Ascochyta viciae, on adipogenesis and obesity. We determined the effects of ASC on 3T3-L1 preadipocytes and whether it ameliorated to mitigate high-fat diet (HFD)-induced obesity in C57BL/6J mice. We found that ASC significantly inhibited the differentiation of preadipocytes by modulating the Wnt/β-catenin signaling pathway, a key regulator of adipogenic processes. Treatment with ASC not only reduced the mRNA and protein expression of key adipogenic transcription factors such as C/EBPα and PPARγ, but also reduced lipid accumulation both in vitro and in vivo. In addition, treatment HFD-fed mice with ASC significantly reduced their weight gain and adiposity vs. control mice. These results suggest that ASC has considerable potential as a therapeutic agent for obesity, owing to its dual action of inhibiting adipocyte differentiation and reducing lipid accumulation. Thus, ASC represents a promising candidate as a natural anti-obesity agent.

Mantidis Ootheca (sangpiaoxiao), the egg case of the mantis, is a type of insect-derived traditional medicine widely used in East Asia. However, species identification based on egg morphology is challenging, leading to the distribution of counterfeit and adulterated products. The use of inauthentic ingredients can pose serious health risks to consumers. This study aimed to develop PCR markers that can rapidly and accurately differentiate between authentic and counterfeit Mantidis Ootheca. The mitochondrial cytochrome c oxidase I (COI) region was sequenced in thirteen samples from four mantis species: Tenodera angustipennis, Statilia maculata, Hierodula patellifera, and T. sinensis. Four sets of SCAR primers were designed based on species-specific nucleotide polymorphisms, and a multiplex SCAR assay was developed by combining all sets of the primers. The sequence-characterized amplified region (SCAR) primers successfully produced amplicons for each target species, even with low-DNA templates or templates containing DNA from multiple samples. No amplification was observed for nontarget species. This study presents a novel approach for identifying authentic Mantidis Ootheca species using DNA-based diagnostic marker assays, which enable rapid and precise species identification. The SCAR assays developed in this study will aid in maintaining quality control and promoting the standardization of commercial Mantidis Ootheca products.

Particulate matter (PM) significantly contributes to the global health crisis of respiratory diseases. It is known to induce and exacerbate conditions such as asthma and respiratory infections. Long exposure to PM can increase the risk of combined allergic rhinitis and asthma syndrome (CARAS). Although therapeutic drugs can be used to improve symptoms of respiratory diseases caused by PM, their usage is often accompanied by side effects. Therefore, many studies are being conducted to discover functional food materials that can more effectively treat respiratory diseases while minimizing the side effects of these therapeutic drugs. This study was conducted to investigate the efficacy of Hydrangea serrata extract (HSE) in airway inflammation in a mouse model of CARAS exacerbated by PM. In the CARAS mouse model worsened by PM, the airway inflammation improvement effect of HSE was evaluated by analyzing allergic nasal symptoms, changes in inflammatory cells, OVA-specific immunoglobulin (Ig) levels, cytokines, mast cell activation, and histopathological findings of both nasal mucosa and lung tissue. HSE effectively reduced OVA-specific IgE and IgG1 and inhibited the production of T helper type 2 (Th2)-related cytokines such as IL-4 and IL-5. Importantly, HSE reduced IL-33 and ST2 expression and inhibited the activation of the NF-κB signaling pathway. In addition, HSE inhibited airway hypersensitivity, mucus production, and inflammatory cell infiltration. These results suggest that HSE may inhibit airway inflammation in CARAS/PM mice by regulating the IL-33/ST2/NF-κB signaling pathway, opening avenues for considering HSE as a potential material for treating allergic airway inflammation diseases in the future.

Abstract Background Allergic rhinitis (AR) is the most prevalent form of atopic disease. Undaria pinnatifida has potent antioxidative, antidiabetic, and anti‐inflammatory properties. Aims We investigated the immunomodulatory effect of Undaria pinnatifida extract (UPE) on allergic inflammation in an AR mouse model. Materials & Methods Mice were sensitized and intranasally challenged with ovalbumin (OVA), and the Th1/Th2 and Th17/Treg‐related cytokines and histopathology were exanimated after UPE treatments. Enzyme‐linked immunosorbent assay was performed using serum samples and NALF to detect OVA‐specific immunoglobulins and inflammatory cytokines. Mitogen‐activated protein kinases (MAPKs) were measured by western blotting analysis, and an in vitro study measured mast cell activation induced by compound 48/80. Results After UPE treatment, nasal and lung allergy symptoms, nasal mucosal swelling, and goblet cell hyperplasia were ameliorated. Oral UPE regulated the balance of Th1/Th2 and Th17/Treg cell differentiation in AR mice in a dose‐dependent manner. In addition, UPE attenuated the migration of eosinophils and mast cells to the nasal mucosa by suppressing nuclear factor kappa B (NF‐κB)/MAPKs. The levels of anti‐OVA IgE and IgG1 were also decreased. Discussion UPE inhibited inflammation by regulating the NF‐κB/MAPKs signaling pathway and supressing the activation of critical immune cells such as eosinophils and mast cells. Conclusion UPE may have therapeutic potential for AR.

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Abstract The safety of laparoscopic gastrectomy compared with that of open surgery for the treatment of early gastric cancer (EGC) is unidentified on a national scale. We aimed to compare the morbidity between laparoscopic and open gastrectomies for pathological T1 gastric cancer based on nationwide survey data. Data of 14,076 patients who underwent gastric cancer surgery obtained from the 2019 Korean Gastric Cancer Association-led nationwide survey were used. For patients with pathological T1 gastric cancer, the clinical characteristics were compared between the laparoscopic and open gastrectomy groups. Propensity score matching (PSM) was performed to match the baseline characteristics of the groups. Among the 7765 patients with pathological T1 gastric cancer who underwent open or laparoscopic gastrectomy, 612 pairs were matched. After balancing the baseline characteristics, the laparoscopic gastrectomy group had a significantly longer operative time, less blood loss, greater number of harvested lymph nodes, shorter hospital stays, and comparable morbidity, compared with the open gastrectomy group (P

Background This study investigated the risk of cause-specific mortality according to glucose tolerance status in elderly South Koreans. Methods A total of 1,292,264 individuals aged ≥65 years who received health examinations in 2009 were identified from the National Health Information Database. Participants were classified as normal glucose tolerance, impaired fasting glucose, newly-diagnosed diabetes, early diabetes (oral hypoglycemic agents ≤2), or advanced diabetes (oral hypoglycemic agents ≥3 or insulin). The risk of system-specific and disease-specific deaths was estimated using multivariate Cox proportional hazards analysis. Results During a median follow-up of 8.41 years, 257,356 deaths were recorded. Diabetes was associated with significantly higher risk of all-cause mortality (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.57 to 1.60); death due to circulatory (HR, 1.49; 95% CI, 1.46 to 1.52), respiratory (HR, 1.51; 95% CI, 1.47 to 1.55), and genitourinary systems (HR, 2.22; 95% CI, 2.10 to 2.35); and neoplasms (HR, 1.30; 95% CI, 1.28 to 1.32). Diabetes was also associated with a significantly higher risk of death due to ischemic heart disease (HR, 1.70; 95% CI, 1.63 to 1.76), cerebrovascular disease (HR, 1.46; 95% CI, 1.41 to 1.50), pneumonia (HR, 1.69; 95% CI, 1.63 to 1.76), and acute or chronic kidney disease (HR, 2.23; 95% CI, 2.09 to 2.38). There was a stepwise increase in the risk of death across the glucose spectrum (P for trend

Abstract Objective Accurate correction is a prerequisite for the favorable outcomes of open-wedge high tibial osteotomy (OWHTO). However, previous studies have reported disappointing results regarding correction accuracy despite the use of intra-operative navigation, which implies that a certain factor other than bony components is involved in the inaccurate correction (mainly overcorrection). The joint-line convergence angle (JLCA) can represent soft tissue effects in OWHTO. This study tried to determine whether the postoperative change in the JLCA (∆JLCA) led to inaccurate correction. Methods Medical records of 78 OWHTO patients from 2005 to 2021 were retrospectively reviewed. The hip–knee–ankle angle (HKA) was measured with a positive value indicating varus alignment. Inaccurate correction was defined as postoperative HKA

Objective: Real-world-based population data about the optimal low-density lipoprotein cholesterol (LDL-C) level for preventing cardiovascular disease in very high-risk populations is scarce. Methods: From 2009 to 2012, 26,922 people aged ≥ 40 years with type 2 diabetes mellitus (T2DM) who had a history of percutaneous coronary intervention (PCI) were analyzed. Data from the Korean National Health Insurance System were used. They were followed up to the date of a cardiovascular event or the time to death, or until December 31, 2018. Endpoints were recurrent PCI, newly stroke or heart failure, cardiovascular death, and all-cause death. Participants were divided into the following categories according to LDL-C level:

Abstract Background Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study. Methods Patients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported. Results Of 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population. Conclusions Upadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure. Trial registration NCT02049138.

Abstract Arachidonic and adrenic acids in the membrane play key roles in ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen reveals that darapladib, an inhibitor of Lp-PLA2, synergistically induces ferroptosis in the presence of GPX4 inhibitors. We show that darapladib is able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, we find that Lp-PLA2 is located in the membrane and cytoplasm and suppresses ferroptosis, suggesting a critical role for intracellular Lp-PLA2. Lipidomic analyses show that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriches phosphatidylethanolamine species and reduces lysophosphatidylethanolamine species. Moreover, combination treatment of darapladib with the GPX4 inhibitor PACMA31 efficiently inhibits tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment.

Abstract Various prospective surgical trials have been conducted on treating patients with gastric cancer. In clinical practice, patients and surgeons may hesitate to participate in prospective surgical trials due to trial-related complications. In this study, we evaluated the effects of participation in prospective surgical trials on surgical outcomes after radical gastrectomy for gastric cancer. This study included 1689 patients who underwent curative gastrectomy for gastric cancer between 2016 and 2020. The propensity score weighting (PSW) method was used to adjust for differences in baseline clinicopathological characteristics between patients who participated and those who did not participate in prospective surgical clinical trials. Perioperative outcomes and overall survival were compared between groups. Of the 1689 patients, 309 (18.3%) participated in surgical clinical trials (SCT group). Before PSW, the SCT group had a similar operation time, intraoperative blood loss, complications, major complications, and hospital stay as the non-SCT group but had superior overall survival. After PSW, overall survival and perioperative outcomes were not significantly different between the groups. The present study suggests that participation in prospective surgical trials was not associated with surgical outcomes. Patients and surgeons may participate in prospective surgical trials without fearing adverse effects on surgical outcomes.

The genus Euconnus Thomson (Coleoptera: Staphylinidae: Scydmaeninae) includes four species in Korea. In this study, E. (s. str.) fustiger and E. (s. str.) dulcis are recorded for the first time Korea and E. (Cladoconnus) rudimentalis is redescribed. As a result, the number of the Korean species of Euconnus is increased to six. A key descriptions, habitus illustrations, diagnostic characters, and a distribution map are provided.

Owing to the massive expansion and intermittent nature of renewable power, green hydrogen production, storage, and transportation technologies with improved economic returns need to be developed. Moreover, the slowness of the dehydrogenation reaction is a primary barrier to the commercialization of liquid organic hydrogen carrier (LOHC) technology. The present study focused on increasing the speed of dehydrogenation, resulting in the proposal of a triple-loop dehydrogenation system comprising reaction, heating, and chilling loops. The reactor has a rotating cage containing a packed bed of catalyst pellets, which is designed to enhance both heat and mass transfer by helping to detach precipitated hydrogen bubbles from the catalyst surface. In addition, the centrifugal force aids in isolating the gas phase from the LOHC liquid. A dehydrogenation experiment was conducted using the reaction and chilling loops, which revealed that the average hydrogen production rate during the first hour was 52.6 LPM (liter per minute) from 26.3 L of perhydro-dibenzyl-toluene with 1.5 kg of 0.5 wt% Pt/Al2O3 catalyst. This was approximately 48% more than the value predicted with the reaction kinetics measured with a small-scale plug flow dehydrogenation reactor with less than 1.0 g of 5.0 wt% Pt/Al2O3 catalyst. The concept, construction methods, and results of the preliminary gas infiltration, flow visualization, and reactor pumping experiments are also described in this paper.

This study examined the performance of reversed Brayton cycle heat pumps to supply heat above 300 °C. The aim was to overcome the current temperature limitations faced by heat pump technology in industrial heat supply sectors by examining the viability of the reversed Brayton cycle. In particular, the effects of the operating conditions on the cycle performance, such as the waste and return heat temperatures, were analyzed through thermal performance analysis. The reversed Brayton cycle heat pumps showed improved performance over conventional vapor compression cycle heat pumps when a heat supply above 215 °C was required. Furthermore, integrating additional heat exchangers into the cycle configuration was proposed in this study as a method to enhance waste heat utilization and recover unused heat from industrial processes. By incorporating preheating and recuperated cycles, these modifications broaden the operational range under the same operating conditions. They also improve the coefficient of performance (COP) of the reference cycle by up to 23% and 27.4%, respectively. This study explored the potential of reversed Brayton cycle heat pumps to supply heat above 300 °C and provided fundamental guidelines for the efficient design and operation of reversed Brayton cycle heat pumps. The results are expected to enhance our understanding of the performance characteristics of reversed Brayton cycle heat pump technology and expand its use as an alternative to fossil-fuel-based heat supply systems.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. The success of modRNA-based COVID-19 vaccines has demonstrated that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases, including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options, and MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and mitigates cardiac dysfunction. However, it remains unclear whether early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. We hypothesized that CCN5 would alleviate the adverse effects of myocardial infarction (MI) through its anti-fibrotic properties under stress conditions. To induce the rapid expression of CCN5, ModRNA-CCN5 was synthesized and administrated directly into the myocardium in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: (1) preventive intervention and (2) therapeutic intervention. Functional analyses, including echocardiography and magnetic resonance imaging (MRI), along with molecular assays, demonstrated that modRNA-mediated CCN5 gene transfer significantly attenuated cardiac fibrosis and improved cardiac function in both preventive and therapeutic models, without causing left ventricular rupture or any adverse cardiac remodeling. In conclusion, early intervention in CF by ModRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure.

Abstract Background Whether migraine is related to the risk of cardiovascular diseases (CVDs) remains unclear. Therefore, we conducted a longitudinal follow-up study to address the association between migraine and the development of CVDs in Korea. Methods Using data from the national health screening cohort, we included 45,246 patients diagnosed with migraine between 2002 and 2019 and age-, sex-, income-, and residential region-matched nonmigraine participants at a ratio of 1:4. Participants with previous CVDs were excluded. Cox proportional hazards regression models were used to estimate the hazard ratios of three CVDs, stroke, ischemic heart disease, and heart failure, in patients with migraine after adjusting for potential cardiovascular risk factors. Results The incidence rate differences of stroke, ischemic heart disease, and heart failure among patients with migraine were 2.61, 1.69, and 0.11, respectively. The probability of developing stroke and ischemic heart disease in patients with migraine was significantly higher than that in controls after controlling for multiple confounders (adjusted hazard ratio [HR] = 1.35, 95% confidence interval [CI] = 1.31–1.39 and adjusted HR = 1.31, 95% CI = 1.26–1.35, respectively). However, when compared with the patients without migraine, patients with migraine did not have an increased HR of developing heart failure (adjusted HR = 1.01, 95% CI = 0.95–1.08). The overall migraine group, as well as groups stratified by migraine subtypes with and without aura, each showed a significantly higher probability of subsequent stroke and ischemic heart disease than the control group. Conclusions Our longitudinal follow-up study demonstrated a significant association between the presence of migraine and the development of stroke and ischemic heart disease in Korea, even after adjusting for cardiovascular risk factors.