Search

Hong-Hua Li,1 Zhi-Da Xu,1,2 Bing Wang,1 Jun-Yan Feng,1 Han-Yu Dong,1 Fei-Yong Jia1,31Department of Developmental and Behavioral Pediatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of China; 2Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands; 3Neurological Research Center of the First Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Fei-Yong JiaDepartment of Developmental and Behavioral Pediatrics, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of ChinaTel +86 04 318 878 3846Email erkekangfujia@163.comPurpose: Vitamin D deficiency has been found in children with chronic tic disorders (CTDs). Our previous data showed that serum 25-hydroxyvitamin D [25(OH)D] level in children with CTDs was lower than that of the healthy controls and lower serum 25(OH)D level was associated with increased severity of the tic disorder. Thus, we intend to further verify this phenomenon and examine the effect of vitamin D3 on CTDs.Patients and methods: In total, 120 children with CTDs and 140 normal controls were enrolled in this study, with 36/120 of those in the CTD group receiving vitamin D3 treatment for 3 months. The Yale Global Tic Severity Scale (YGTSS) and Clinical Global Impression of Severity of Illness (CGI-SI) were, respectively, used to evaluate the tic severity. High-performance liquid chromatography and tandem mass spectrometry were used to measure serum 25(OH)D level.Results: Those children with CTDs exhibited significantly lower 25(OH)D levels than did healthy controls, and these reduced 25(OH)D levels were linked to increasing severity of tic symptoms. After treatment with supplemental vitamin D3, serum 25(OH)D level and scores of YGTSS total, motor tics, phonic tics, total tic, impairment, and CGI-SI improved significantly in children with CTDs without any adverse reactions.Conclusion: Supplementation vitamin D3, given its low cost and excellent safety, may be an effective means of improving symptoms in certain children with CTDs.Keywords: vitamin D, chronic tic disorders, 25(OH)D, dopamine, child

Purpose: To evaluate the feasibility of a three-point flanged optic piercing intrascleral fixation technique for replacing a dislocated multifocal intraocular lens (IOL). Design: Retrospective cross-sectional study. Methods: In total, 13 eyes from 13 patients with a dislocated single-piece C-loop or double C-loop diffractive multifocal IOL were enrolled to undergo dislocated multifocal IOL replacement through three-point flanged optic piercing 120 degrees apart intrascleral fixation using 7-0 polypropylene sutures at 2.5 mm posterior to the limbus. Preoperative and postoperative uncorrected distance visual acuity (UDVA), postoperative uncorrected intermediate visual acuity (UIVA) at 66 cm, uncorrected near visual acuity (UNVA) at 40 cm, residual refractive errors, and the amount of IOL decentration were evaluated. Results: There were six multifocal IOLs and seven multifocal toric IOLs. There was a notable improvement in visual acuity, with the mean UDVA improving from 0.79 ± 0.72 logMAR preoperatively to 0.06 ± 0.08 logMAR postoperatively (P = 0.004). The mean postoperative UIVA and UNVA were 0.04 ± 0.05 and 0.10 ± 0.12 logMAR, respectively. The mean residual refractive sphere, cylinder, and spherical equivalent were −0.04 ± 0.48 D, −0.29 ± 0.25 CD, and −0.18 ± 0.47 D, respectively. The mean residual cylinder was −0.25 ± 0.25 CD in eyes with multifocal toric IOL fixation. The mean amount of IOL decentration was 0.22 ± 0.05 mm. Conclusion: The three-point flanged optic piercing intrascleral fixation technique for dislocated multifocal IOLs could provide good distance, intermediate, and near vision alongside excellent IOL centration.

Abstract Interplay between charge density wave (CDW) order and superconductivity (SC) in quasi-two-dimensional materials remains poorly understood due to their diverse experimental varieties. Here, we investigate the pressure-dependent electrical transport and Raman scattering spectra of 2H-Pd0.05TaSe2, which exhibits a CDW transition at T CDW = 115 K and a superconducting transition at T c = 2.6 K at ambient pressure conditions. As pressure increases, T CDW, identified by the resistivity anomaly, shifts towards lower temperatures and approaches zero at a critical pressure of P c ~ 21.5 GPa. At this critical pressure, both T c and upper critical field H c2 reach their maximum values of ~ 8.5 K and ~ 6.4 T, respectively. Analysis of the Raman scattering spectra demonstrates that increasing pressure systematically suppresses both the two-phonon spectral weight above T CDW and the CDW amplitudon energies below T CDW, leading to their simultaneous disappearance at P c. These observations provide direct evidence for the formation of a CDW quantum critical point (QCP) at P c, indicating that charge and lattice fluctuations associated with the QCP of strongly coupled CDW order may enhance SC in pressurized 2H-Pd0.05TaSe2.

Abstract To evaluate the effects of orthoptic training using a virtual reality (VR) head-mounted display game in patients with intermittent exotropia (IXT), a prospective, randomized, double-blind study was performed in 62 patients ≥ 13 years with IXT of ≥ 8 prism diopters (∆) and with a near ≥ distance angle, i.e., basic type and convergence insufficiency-type IXT. Patients were randomly assigned to a video-game group that induced convergence (exercise group) and a placebo-game group not inducing convergence (control group), and completed the program 15 min/day for 4 weeks. Subjective symptom scores, angle of exodeviation, near point of convergence, stereoacuity, fusional control scores using the Newcastle Control Score (NCS) and the Office Control Score (OCS) were noted. Outcome measures were assessed after 4 weeks, and re-evaluated after a washout period of 4 weeks. After using the VR game for 4 weeks, the near angle of exodeviation significantly decreased from 29.6 ± 9.5∆ to 25.3 ± 9.0∆ in the exercise group (p

Background/Aims: Studies on the clinical outcomes after detecting low-grade dysplasia (LGD) in patients with inflammatory bowel disease (IBD) are insufficient. This study evaluated the clinical features, frequency, and risk factors for advanced neoplasia in patients with IBD after an LGD diagnosis. Methods: The medical records of 166 patients with IBD from six university hospitals in Korea from 2010 to 2019 were reviewed retrospectively. LGD was diagnosed in all patients during surveillance. The frequency and risk factors for advanced neoplasia were evaluated, and the clinical features of patients with and without advanced neoplasia were compared. Results: Advanced neoplasia developed in 12 patients (six with large LGD, three with tubulovillous adenoma, and three with high-grade dysplasia), and all cases developed from UC. Patients with advanced neoplasia had significantly higher Mayo scores, and colitis-associated dysplasia was more common than sporadic lesions (83.3% vs. 29.9%; p

Hepatic tuberculosis, typically associated with miliary tuberculosis, can occasionally present as localized liver lesions. This case report describes a 77-year-old male presenting with persistent abdominal pain and fever, following an endoscopic retrograde cholangiopancreatography for bile duct sludge removal. Subsequent computed tomography revealed focal liver lesions. Despite initial treatment with antibiotics for a suspected inflammatory liver abscess, his condition did not improve. A liver biopsy was performed, revealing caseous granulomas, and the tuberculosis polymerase chain reaction result was positive. The patient was diagnosed with primary hepatic tuberculosis, which later disseminated. Oral anti-tuberculosis therapy was initiated and is currently being closely monitored. This case emphasizes the importance of considering hepatic tuberculosis in the differential diagnosis of liver lesions, particularly in cases involving cholestatic liver function tests, and persistent symptoms unresponsive to conventional antibiotics.

Primary cholangiocarcinoma is a rare bile duct epithelial neoplasm that can present with atypical clinical manifestations, complicating its diagnosis. A 62-year-old male showed symptoms suggestive of a complicated hepatic cyst that was later identified as intrahepatic cholangiocarcinoma. The patient presented with abdominal discomfort without fever. Imaging revealed a large cystic lesion in the liver. Despite the initial treatment for a presumed abscess, a biopsy confirmed cholangiocarcinoma. This case highlights the diagnostic challenge of distinguishing between benign complicated hepatic cysts and malignancies, particularly when typical markers of infection are absent. Early biopsy and vigilant assessments are crucial in such presentations to avoid a delayed diagnosis and initiate appropriate treatment.

Abstract Increasing the proximity of microelectrode arrays (MEA) to targeted neural tissues can establish efficient neural interfaces for both recording and stimulation applications. This has been achieved by constructing protruding three-dimensional (3D) structures on top of conventional planar microelectrodes via additional micromachining steps. However, this approach adds fabrication complexities and limits the 3D structures to certain shapes. We propose a one-step fabrication of MEAs with versatile microscopic 3D structures via “microelectrothermoforming (μETF)” of thermoplastics, by utilizing 3D-printed molds to locally deform planar MEAs into protruding and recessing shapes. Electromechanical optimization enabled a 3D MEA with 80 μm protrusions and/or recession for 100 μm diameter. Its simple and versatile shaping capabilities are demonstrated by diverse 3D structures on a single MEA. The benefits of 3D MEA are evaluated in retinal stimulation through numerical simulations and ex vivo experiments, confirming a threshold lowered by 1.7 times and spatial resolution enhanced by 2.2 times.

Background Sarcopenia is a muscle-wasting condition that affects older individuals. It can lead to changes in movement patterns, which can increase the risk of falls and other injuries. Methods Older women participants aged ≥65 years who could walk independently were recruited and classified into two groups based on knee extension strength (KES). Participants with low KES scores were assigned to the possible sarcopenia group (PSG; n=7) and an 8-week exercise intervention was implemented. Healthy seniors with high KES scores were classified as the reference group (RG; n=4), and a 3-week exercise intervention was conducted. Kinematic movement data were recorded during the intervention period. All participants' exercise repetitions were used in the data analysis (number of data points=1,128). Results The PSG showed significantly larger movement patterns in knee rotation during wide squats compared to the RG, attributed to weakened lower limb strength. The voting classifier, trained on the movement patterns from wide squats, determined that significant differences in overall movement patterns between the two groups persisted until the end of the exercise intervention. However, after the exercise intervention, significant improvements in lower limb strength in the PSG resulted in reduced knee rotation range of motion and max, thereby stabilizing movements and eliminating significant differences with the RG. Conclusion This study suggests that exercise interventions can modify the movement patterns in older individuals with possible sarcopenia. These findings provide fundamental data for developing an exercise management system that remotely tracks and monitors the movement patterns of older adults during exercise activities.

Abstract Efficient light generation from triplet states of organic molecules has been a hot yet demanding topic in academia and the display industry. Herein, we propose a strategy for developing triplet emitter by creating heterostructures of organic chromophores and transition metal dichalcogenides (TMDs). These heterostructures emit microsecond phosphorescence at room temperature, while their organic chromophores intrinsically exhibit millisecond phosphorescence under vibration dissipation-free conditions. This enhancement in phosphorescence is indicative of significantly enhanced spin-orbit coupling efficiency through coupling with TMDs. Through detailed studies on these hybrids from various perspectives, we elucidate key features of each component essential for generating microsecond triplet emission, including 2H-TMDs with heavy transition metals and aromatic carbonyl with an ortho-hydroxy group. Our intriguing findings open avenues for exploring the universal applicability of fast and stable hybrid triplet emitters.

Medical school professors take on many roles, including teaching, research, service, and practice, and are expected to evolve through their work and activities both on and off campus. At the same time, they are expected to gradually develop essential competencies as educators through faculty development (FD). However, FD does not yet cover the entire spectrum of faculty roles and does not adequately address the diverse characteristics of medical school faculty. In light of the recent interest in FD in Korean medical schools and an increasing number of articles on FD, I here review the history of and recent articles about FD in Korea. I also suggest seven short- and long-term strategies to overcome the major challenges facing FD, with the aim of helping to revitalize and advance FD in Korean medical schools and FD institutions.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by skin and internal organ fibrosis and obliterative vasculopathy. Few effective treatments are currently available for fibrosis in SSc, therefore, demand persists for novel therapies. Although use of Ginkgo biloba extract (GBE) has been reported to improve blood circulation and alleviate liver and lung fibrosis, its effect on skin fibrosis in SSc remains unclear. In this study, the effects and underlying mechanisms of GBE on skin fibrosis in bleomycin (BLM)-induced mouse model of SSc was investigated. GBE significantly reduced dermal thickness and protein levels of profibrotic factors in the BLM-induced SSc mouse model. Moreover, GBE inhibited the gene expression of profibrotic factors, such as COL1A1, α-SMA, and connective tissue growth factor (CTGF), in fibroblasts by suppressing transforming growth factor (TGF)-β signaling. Furthermore, GBE inhibited the transdifferentiation of adipocytes into myofibroblasts. Thus, our findings suggest that GBE is a promising therapeutic candidate for the treatment of SSc.

Abstract Background Staphylococcus hyicus causes porcine exudative epidermitis, predominantly affecting suckling and weaned piglets. This bacterium produces various exfoliative toxins (ExhA, ExhB, ExhC, ExhD, SHETA, and SHETB), which are responsible for the clinical manifestations of exudative epidermitis. However, treatment failure is common due to frequent antimicrobial resistance in porcine strains. Therefore, this study aimed to identify the genes encoding exfoliative toxins and assess the antimicrobial resistance profiles of S. hyicus. A total of 17 S. hyicus isolates were collected from piglets with skin lesions from 2014 to 2021. All strains were subjected to species-specific polymerase chain reaction targeting sodA to confirm the presence of S. hyicus, and polymerase chain reaction amplification of exfoliative toxin genes (exhA, exhB, exhC, exhD, sheta, and shetb) was performed to differentiate toxigenic strains. Pulsed-field gel electrophoresis analysis and minimum inhibitory concentration tests using broth microdilution were conducted to further analyze the strains. Results Exfoliative toxin genes were detected in 52.9% (n = 9) of the S. hyicus isolates, with notable detection of exhB (17.6%), exhC (17.6%), exhD (11.8%), exhA (5.9%), sheta (0%), and shetb (0%). Pulsed-field gel electrophoresis analysis categorized the isolates into 11 pulsotypes with 70% similarity. Among 18 tested antimicrobials, all isolates exhibited 100% susceptibility to ceftiofur and sulfonamides and high susceptibility rates to neomycin, tilmicosin, and tetracyclines. Whereas the susceptibility rate of spectinomycin was 0% in all isolates, multidrug resistance was observed in 82.4% of the isolates, and in all toxigenic strains. Conclusions These findings provide crucial insights for monitoring and devising effective treatment strategies for managing exudative epidermitis in pigs caused by S. hyicus.

Cardiac rupture is a rare but fatal complication among patients undergoing cardiopulmonary resuscitation (CPR). Myocardial rupture can manifest as a discontinuity in the myocardial wall, communication between the ventricle or atrium and the pericardium, hemopericardium, or active extravasation of contrast into the pericardium. It can also occur alongside pericardial rupture or hemothorax. Diagnosing myocardial rupture via imaging is uncommon due to its clinical urgency and high mortality rate. We present a rare case of a 50-yearold man who developed a right atrial rupture, as seen on CT angiography, following CPR and venoarterial extracorporeal membrane oxygenation (VA-ECMO) for sudden cardiac arrest.

Abstract Malnutrition is a significant risk factor for postoperative outcomes in patients undergoing cardiac surgery. The Seoul National University Hospital-Nutrition Screening Index (SNUH-NSI) is an automated screening tool designed to comprehensively assess malnutrition risk. However, its predictive value in patients undergoing cardiac surgery remains unvalidated. This study included adult patients who underwent cardiac surgery at a tertiary teaching hospital between May 2008 and December 2019. Patients were classified as low-, intermediate-, or high-risk for malnutrition based on the SNUH-NSI. The association between malnutrition risk and postoperative cumulative all-cause mortality was evaluated using multivariable Cox regression analysis. The predictive ability of the SNUH-NSI was compared with conventional nutritional indices. Compared to the low-risk group, both the high-risk (adjusted hazard ratio [HR], 2.64; 95% confidence interval [CI], 2.19–3.19; P

Abstract Little is known about changes in the abundance of tumor-infiltrating lymphocytes (TILs) and immune phenotype (IP) in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). We aimed to compare the TILs and IP between initial and recurrent HNSCCs using paired analysis. Thirty-seven patients who experienced recurrence after surgical resection and received treatment with immune checkpoint inhibitors (ICIs) between June 2014 and June 2023 were included. Changes in intratumoral TIL (iTILs), stromal TIL (sTILs), and IPs were subjected to paired analysis between the initial and recurrent tumors. We investigated their relationship with the outcomes of ICIs. The density of iTIL and sTIL in the recurrent tumors was significantly lower compared to initial tumors. IP was significantly different; the proportion of desert IP was higher in recurrent tumors (83.8% vs. 35.1%, P

Abstract Chimeric antigen receptor T (CAR-T) cells show remarkable efficacy for some hematological malignancies. However, CAR targets that are expressed at high level and selective to tumors are scarce. Several strategies have been proposed to tackle the on-target off-tumor toxicity of CAR-T cells that arise from suboptimal selectivity, but these are complicated, with many involving dual gene expression for specificity. In this study, we show that switchable CAR-T cells with a tumor targeting adaptor can mitigate on-target off-tumor toxicity against a low selectivity tumor antigen that cannot be targeted by conventional CAR-T cells, such as CD40. Our system is composed of anti-cotinine murine CAR-T cells and cotinine-labeled anti-CD40 single chain variable fragments (scFv), with which we show selective tumor killing while sparing CD40-expressing normal cells including macrophages in a mouse model of lymphoma. Simple replacement of the tumor-targeting adaptor with a suicidal drug-conjugated tag may further enhance safety by enabling permanent in vivo depletion of the switchable CAR-T cells when necessary. In summary, our switchable CAR system can control CAR-T cell toxicity while maintaining therapeutic efficacy, thereby expanding the range of CAR targets.

Abstract Low-frequency noise (LFN) characteristics of semiconductor devices pose a significant importance for understanding their working principle, particularly concerning material imperfections. Accordingly, substantial research endeavors have focused on characterizing the LFN of devices. However, the LFN characteristics of the ambipolar transistors have been rarely demonstrated. Herein, we investigate the effects of ambipolar carrier transport and CYTOP-induced p-type doping on low-frequency noise characteristics of MoTe2 transistors. The source of the 1/f noise differs between the n-type (electron transport) and p-type (hole transport) modes. Notably, the influence of contact resistance is more pronounced in the n-type mode. CYTOP doping suppresses the n-type mode by introducing hole doping effects. Furthermore, CYTOP doping mitigates the impact of contact resistance on excess noise.

Abstract The present study was designed to identify the preoperative clinical and imaging findings influencing adverse clinical outcomes in patients with chronic constrictive pericarditis after pericardiectomy. Patients with constrictive pericarditis who underwent pericardiectomy between January 2009 and September 2023 were retrospectively analyzed. Preoperative evaluations included assessments of clinical symptoms, comorbidities, laboratory tests, cardiac computed tomography (CT), and transthoracic echocardiography. The volume of pericardial calcifications was quantified on calcium scoring CT. Adverse clinical events were defined as cardiovascular death or hospitalization due to cardiac causes, and all-cause mortality was assessed. Univariable and multivariable Cox proportional hazard model analysis were performed to find factors associated with adverse clinical events. Among the 91 patients with available preoperative CT scans, 26 (28.6%) experienced adverse clinical events after pericardiectomy, with 19 (20.9%) experiencing cardiovascular deaths. On multivariable Cox analysis, larger pericardial calcium volume hazard ratio [HR], 1.004 (95% confidence interval [CI], 1.001–1.006) per 1cm3 increase; p = 0.005), higher E/E’ ratio (HR, 1.059, 95% CI, 1.015–1.105, p = 0.008), and lower albumin level (HR, 0.476, 95% CI, 0.229–0.986, p = 0.046) were significant factors associated with the adverse clinical events after pericardiectomy. The amount of pericardial calcification could be associated with the efficacy of pericardiectomy and potentially have implications for postoperative outcomes. Additionally, a high E/E ratio on echocardiography is indicative of unfavorable postoperative prognosis.

Background/Aims: Combi-elastography is a B-mode ultrasound-based method in which two elastography modalities are utilized simultaneously to assess metabolic dysfunction-associated steatotic liver disease (MASLD). However, the performance of combi-elastography for diagnosing metabolic dysfunction-associated steatohepatitis (MASH) and determining fibrosis severity is unclear. This study compared the diagnostic performances of combi-elastography and vibration-controlled transient elastography (VCTE) for identifying hepatic steatosis, fibrosis, and high-risk MASH.Methods: Participants who underwent combi-elastography, VCTE, and liver biopsy were selected from a prospective cohort of patients with clinically suspected MASLD. Combi-elastography-related parameters were acquired, and their performances were evaluated using area under the receiver-operating characteristic curve (AUROC) analysis.Results: A total of 212 participants were included. The diagnostic performance for hepatic steatosis of the attenuation coefficient adjusted by covariates from combi-elastography was comparable to that of the controlled attenuation parameter measured by VCTE (AUROC, 0.85 vs 0.85; p=0.925). The performance of the combi-elastography-derived fibrosis index adjusted by covariates for diagnosing significant fibrosis was comparable to that of liver stiffness measured by VCTE (AUROC, 0.77 vs 0.80; p=0.573). The activity index from combi-elastography adjusted by covariates was equivalent to the FibroScan-aspartate aminotransferase score in diagnosing high-risk MASH among participants with MASLD (AUROC, 0.72 vs 0.74; p=0.792).Conclusions: The performance of combi-elastography is similar to that of VCTE when evaluating histology of MASLD.

Abstract The Coronavirus disease 2019 (COVID-19) pandemic has led to a global health crisis, including ocular symptoms, primarily targeting the Angiotensin-Converting Enzyme 2 (ACE2) receptor. PM2.5 air pollution may increase infection risk by altering ACE2 expression. Silicon Dioxide (SiO2) and carbon black (CB), major components of PM2.5 from sands and vehicle emissions, were studied for their effects on ACE2 and Transmembrane Protease Serine 2 (TMPRSS2) expression in corneal and conjunctival cells, and ocular tissues. Human corneal epithelial cells (HCECs) and conjunctival epithelial cells (HCjECs) were exposed to nanoparticles (NPs) for 24 hours, assessing viability via WST-8 assay. TNF-α, IL-6, and IL-1β levels in the medium were measured. An in vivo rat study administered NPs via eye drops, with Rose Bengal staining to evaluate damage. ACE2, TMPRSS2, and Angiotensin II (AngII) protein expressions were quantified by Western blot. ACE2 expression in HCjECs increased with NP exposure, while it decreased in HCECs. CB exposure increased TNF-α, IL-6, and IL-1β levels in HCECs. In vivo, corneal exposure to CB decreased ACE2 expression, whereas conjunctival exposure to SiO2 increased ACE2 expression. These changes suggest that SiO2 exposure may increase the risk of COVID-19 through the ocular surface, while CB exposure may decrease it.

Abstract This study aimed to investigate the short-term variability of ocular biometric measurements and to analyze the factors associated with high variability of biometric values in patients with cataract. This retrospective study included 60 eyes of 60 patients who underwent ocular biometry twice with the IOLMaster 700 (March to November 2023). Ocular surface parameters included tear film break-up time (TBUT), corneal and conjunctival staining scores (CSS/ConSS). Refractive surprise was defined as a mean absolute error exceeding 0.5 diopter (D). Participants included 22 men and 38 women with a mean age of 70.6 ± 8.4 years. The variability of mean keratometric (K) values and astigmatism showed notable variability compared to axial length (mean K: 0.18 ± 0.17D, astigmatism: 0.21 ± 0.26D, axial length: 0.01 ± 0.01 mm). A decreased TBUT and increased CSS were significantly associated with high variability (≥ 0.25D) of mean K (p = 0.040/0.008). The high K variability group (≥ 0.25D) revealed a significantly higher incidence of refractive surprise (> 0.5D) compared with the low K variability group (

Abstract Background Resistance acquired after radiotherapy is directly related to the failure of various cancer treatments, including GBM. Because the mechanism for overcoming radioresistance has not yet been clearly identified, the development of diagnostic and therapeutic markers to treat radioresistance is necessary. Since increased expression of stemness- and EMT-related markers are reported to be closely correlated with radioresistance, research is underway to develop new drugs targeting these factors. Methods To develop an anticancer drug that overcomes radioresistance, a library of drugs already approved by the FDA was used. After treating radioresistant GBM cells with each drug, the expression of stemness- and EMT-related markers was confirmed by qRT-PCR, and as a result, Atomoxetine (ATX) was selected. It was confirmed that radioresistance-induced cell migratory, invasive, sphere formation abilities, and tumor growth using a xenograft mouse model were suppressed upon ATX treatment. Using a miRNA prediction tool, we discovered miR-520d-5p, which targets Notch2 and Hey1, key factors in radioresistance, and discovered circATIC targeting this miRNA, revealing its relationship with ATX. We demonstrated the expression regulation mechanism and signaling mechanism between circATIC, miR-520d-5p, Notch2, and Hey1 factors using a luciferase reporter assay. In addition, the results at the cellular level were clinically verified by confirming the correlation between radiation, miR-520d-5p, and circATIC using patient plasma by qRT-PCR. Results ATX showed potential as a treatment for radioresistance by suppressing the malignant phenotype by regulating the circATIC/miR-520d-5p/Notch2-Hey1 signaling mechanism in vitro and in vivo using radioresistant GBM cells. Conclusions This study revealed that ATX suppresses radioresistance through the circATIC/miR-520d-5p/Notch2-Hey1 signaling pathway. These results showed the potential of ATX as a new drug that can overcome radioresistance, a major challenge in cancer treatment, and the signaling factors identified in this mechanism suggest the possibility of use as potential targets for the diagnosis and treatment of radioresistance.

Background/Aims Non-alcoholic fatty liver disease (NAFLD), now the most common chronic liver worldwide, has become a significant public health concern. This study aims to analyze the evolving epidemiology of NAFLD in South Korea. Methods We utilized claim data from the Korean National Health Insurance Service from 2010 to 2022 to analyze NAFLD’s incidence, prevalence, and progression. Results From 2010 to 2022, the incidence and prevalence rates of NAFLD each increased from 1.87% to 4.47% and from 10.49% to 17.13%, respectively. The differences in prevalence rates between urban and rural areas were minimal in 2012 and 2022, yet both areas showed significant increases in the prevalence of NAFLD over the decade. The NAFLD group had a higher prevalence of comorbidities compared to the control group, and the most common comorbid condition was hypertension. Moreover, the ten-year incidence rates of malignancy, heart disease, and stroke in the NAFLD group were 13.42%, 15.72%, and 8.36%, respectively, which were significantly higher than those in the control group. The incidence rates of cirrhosis and hepatocellular carcinoma in NAFLD over 10 years were 2.22% and 0.77%, respectively. The total medical costs of NAFLD patients more than doubled over ten years and were all significantly higher than those of the control group. Conclusions A significant increase in NAFLD prevalence and its impact on healthcare utilization was observed in South Korea. With NAFLD leading to serious liver diseases and increased healthcare costs, integrated care strategies that include both medical treatment and lifestyle modifications are essential.

Purpose: This study evaluated the effectiveness of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) treatments using multiple pharmaceutical agents that could simultaneously preserve or enhance fertility capability. Materials and Methods: This was a single-center-based, randomized controlled study, whereas the final analysis evaluated a total 350 CP/CPPS patients (age range, 28–40 years) and 50 patients were randomly allocated to each therapeutic group, with a 1:1 ratio. The therapeutic groups consist of tadalafil (group 1, 5 mg daily), L-carnitine (group 2, 2 g daily), Serenoa repens extract (group 3, 320 mg daily), group 4 (tadalafil+L-carnitine), group 5 (tadalafil+S. repens), group 6 (L-carnitine+S. repens), and group 7 (tadalafil+L-carnitine+S. repens). The treatment outcomes at 3 months post-therapy were analyzed. Results: At 3 months post-therapy, the mean total sperm motility was significantly improved in all groups. A normal morphology improvement was observed in L-carnitine receiving groups. The mean total score on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the mean International Prostate Symptom Score (IPSS) showed the greatest reduction in intensity in group 7. Logistic regression analyses showed that group 5 and group 7 were significantly associated with improvements in total IPSS and total NIH-CPSI scores at 3 months post-therapy. Group 7 was a significant predictor for improving total sperm motility, leukocytospermia and normal form of sperm. Conclusions: Tadalafil, carnitine, and S. repens combination therapy could be considered a feasible treatment option for CP/CPPS males with subfertility.

Background/Aims Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction–associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD. Methods Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction–associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing. Results Methylome and transcriptome analyses of liver biopsies revealed significant (P

Background/Objective: The rapid aging of Korea's population underscores the urgent need for effective programs to enhance the well-being and longevity of the elderly. This study presents preliminary results from the Korean project, examining the impact of cost-effective and accessible exercise programs on functional performance of older people and to determine the long-term maintenance of intervention. Methods: We randomized 90 older adults aged ≥65 years to the walking group (WG), resistance + walking (RWG), or active control (CG) group. We designed a 12-week main intervention (supervised resistance training 2 d/week and individual walking exercise) and a 12-week follow-up through self-directed exercise (same protocol but unsupervised). The participants’ mini mental state examination, color-word Stroop test and 5-time sit to stand, timed up & go, handgrip strength, and knee extensor strength tests were assessed at pre, post, as well as follow-up. Results: For the RWG group, significant improvements were found in timed up & go (P

Background The selection of statistical analysis methods in research is a critical and nuanced task that requires a scientific and rational approach. Aligning the chosen method with the specifics of the research design and hypothesis is paramount, as it can significantly impact the reliability and quality of the research outcomes. Methods This study explores a comprehensive guideline for systematically choosing appropriate statistical analysis methods, with a particular focus on the statistical hypothesis testing stage and categorization of variables. By providing a detailed examination of these aspects, this study aims to provide researchers with a solid foundation for informed methodological decision making. Moving beyond theoretical considerations, this study delves into the practical realm by examining the null and alternative hypotheses tailored to specific statistical methods of analysis. The dynamic relationship between these hypotheses and statistical methods is thoroughly explored, and a carefully crafted flowchart for selecting the statistical analysis method is proposed. Results Based on the flowchart, we examined whether exemplary research papers appropriately used statistical methods that align with the variables chosen and hypotheses built for the research. This iterative process ensures the adaptability and relevance of this flowchart across diverse research contexts, contributing to both theoretical insights and tangible tools for methodological decision-making. Conclusions This study emphasizes the importance of a scientific and rational approach for the selection of statistical analysis methods. By providing comprehensive guidelines, insights into the null and alternative hypotheses, and a practical flowchart, this study aims to empower researchers and enhance the overall quality and reliability of scientific studies.

Abstract On-scene resuscitation time is associated with out-of-hospital cardiac arrest (OHCA) outcomes. We developed and validated reinforcement learning models for individualized on-scene resuscitation times, leveraging nationwide Korean data. Adult OHCA patients with a medical cause of arrest were included (N = 73,905). The optimal policy was derived from conservative Q-learning to maximize survival. The on-scene return of spontaneous circulation hazard rates estimated from the Random Survival Forest were used as intermediate rewards to handle sparse rewards, while patients’ historical survival was reflected in the terminal rewards. The optimal policy increased the survival to hospital discharge rate from 9.6% to 12.5% (95% CI: 12.2–12.8) and the good neurological recovery rate from 5.4% to 7.5% (95% CI: 7.3–7.7). The recommended maximum on-scene resuscitation times for patients demonstrated a bimodal distribution, varying with patient, emergency medical services, and OHCA characteristics. Our survival analysis-based approach generates explainable rewards, reducing subjectivity in reinforcement learning.

Abstract Background Shock is a life‐threatening condition that is associated with high mortality and morbidity. Therefore, the timely identification and management of this condition are important. We aimed to develop a prediction model for vasopressor use based on concise serial arterial blood pressure data. Methods We collected continuous arterial blood pressure from patients admitted to the emergency department (ED) resuscitation room. Patients with an initial systolic blood pressure lower than 90 mmHg were included in the study. We developed prediction models using convolutional neural networks (CNNs) and long short‐term memory (LSTM) networks. Discrimination performance was assessed using the area under the receiver operating characteristic curve (AUROC) and the area under the precision–recall curve (AUPRC). Results A total of 120 patients were enrolled in the study. The CNN and LSTM models yielded AUROCs ranging from 0.731 to 0.834 for predicting the need for vasopressor infusion within different time frames (30 min, 1 h, and 6 h). LSTM outperformed the CNN in terms of predicting vasopressor infusion within 30 min and 1 h (p value

Abstract Background This study aimed to determine the proportion of organ donors suitable for donation after circulatory death and investigate the current process followed by critical care physicians for declaring circulatory death to establish organ donation. Methods This observational study involved potential organ donors who had recently died after discontinuation of life support. We conducted an online survey of intensivists to determine how these deaths were confirmed. Results Among the 177 patients who died after withdrawal of life-sustaining treatment across 19 intensive care units in 11 institutions, 49 (27.7%) were considered potential donors. According to general medical criteria for organ donation, 20 (11.3%) patients were identified as medically suitable donors. Notably, 116 (73.9%) patients exhibited a flat electrocardiogram within 5 min after the loss of pulse. In the survey, 90 physicians (59.2%) agreed to implement the concept of the 5-min no-touch period for the declaration of circulatory death. Conclusions This study found that 11.3% of the patients who died following the withdrawal of life-sustaining treatment in the intensive care units were identified as suitable donors after circulatory death. Most of critical care physicians agree with the concept of a 5-min no-touch period for the declaration of circulatory death.

Abstract Coronary artery calcium (CAC) scoring CT is a useful tool for screening coronary artery disease and for cardiovascular risk stratification. However, its efficacy in patients with coronary stents, who had pre-existing coronary artery disease, remains uncertain. Historically, CAC CT scans of these patients have been manually excluded from the CAC scoring process, even though most of the CAC scoring process is now fully automated. Therefore, we hypothesized that automating the filtering of patients with coronary stents using artificial intelligence could streamline the entire CAC workflow, eliminating the need for manual intervention. Consequently, we aimed to develop and evaluate a deep learning-based coronary stent filtering algorithm (StentFilter) in CAC scoring CT scans using a multicenter CAC dataset. We developed StentFilter comprising two main processes: stent identification and false-positive reduction. Development utilized 108 non-enhanced echocardiography-gated CAC scans (including 74 with manually labeled stents), and for false positive reduction, 2063 CAC scans with significant coronary calcium (average Agatston score: 523.8) but no stents were utilized. StentFilter’s performance was evaluated on two independent internal test sets (Asan cohort- and 2; n = 355 and 396; one without coronary stents) and two external test sets from different institutions (n = 105 and 62), each with manually labeled stents. We calculated the per-patient sensitivity, specificity, and false-positive rate of StentFilter. StentFilter demonstrated a high overall per-patient sensitivity of 98.8% (511/517 cases with stents) and a false-positive rate of 0.022 (20/918). Notably, the false-positive ratio was significantly lower in the dataset containing stents (Asan cohort-1; 0.008 [3/355]) compared with the dataset without stents (Asan cohort-2; 0.043 [17/396], p = 0.008). All false-positive identifications were attributed to dense coronary calcifications, with no false positives identified in extracoronary locations. The automated StentFilter accurately distinguished coronary stents from pre-existing coronary calcifications. This approach holds potential as a filter within a fully automated CAC scoring workflow, streamlining the process efficiently.

Abstract Background Although the representative treatment for colorectal cancer (CRC) is radiotherapy, cancer cells survive due to inherent radioresistance or resistance acquired after radiation treatment, accelerating tumor malignancy and causing local recurrence and metastasis. However, the detailed mechanisms of malignancy induced after radiotherapy are not well understood. To develop more effective and improved radiotherapy and diagnostic methods, it is necessary to clearly identify the mechanisms of radioresistance and discover related biomarkers. Methods To analyze the expression pattern of miRNAs in radioresistant CRC, sequence analysis was performed in radioresistant HCT116 cells using Gene Expression Omnibus, and then miR-1226-5p, which had the highest expression in resistant cells compared to parental cells, was selected. To confirm the effect of miR-1226-5 on tumorigenicity, Western blot, qRT-PCR, transwell migration, and invasion assays were performed to confirm the expression of EMT factors, cell mobility and invasiveness. Additionally, the tumorigenic ability of miR-1226-5p was confirmed in organoids derived from colorectal cancer patients. In CRC cells, IRF1, a target gene of miR-1226-5p, and circSLC43A1, which acts as a sponge for miR-1226-5p, were discovered and the mechanism was analyzed by confirming the tumorigenic phenotype. To analyze the effect of tumor-derived miR-1226-5p on macrophages, the expression of M2 marker in co-cultured cells and CRC patient tissues were confirmed by qRT-PCR and immunohistochemical (IHC) staining analyses. Results This study found that overexpressed miR-1226-5p in radioresistant CRC dramatically promoted epithelial-mesenchymal transition (EMT), migration, invasion, and tumor growth by suppressing the expression of its target gene, IRF1. Additionally, we discovered circSLC43A1, a factor that acts as a sponge for miR-1226-5p and suppresses its expression, and verified that EMT, migration, invasion, and tumor growth are suppressed by circSLC43A1 in radioresistant CRC cells. Resistant CRC cells-derived miR-1226-5p was transferred to macrophages and contributed to tumorigenicity by inducing M2 polarization and secretion of TGF-β. Conclusions This study showed that the circSLC43A1/miR-1226-5p/IRF1 axis is involved in radioresistance and cancer aggressiveness in CRC. It was suggested that the discovered signaling factors could be used as potential biomarkers for diagnosis and treatment of radioresistant CRC.

Gene editing by CRISPR-Cas9 via homology-directed repair (HDR) offers precise and desirable modifications, but its low efficiency remains a challenge due to the dominance of the non-homologous end joining (NHEJ) pathway in DNA repair. To identify compounds that improve HDR-associated gene editing efficiency, we established a high-throughput screening system capable of detecting HDR events and assessing cell viability simultaneously, excluding drugs with severe cytotoxicity. We screened 2485 compounds from a clinical collection library and identified several histone deacetylase inhibitors that significantly enhance HDR efficiency. Tacedinaline and entinostat exhibited the high efficiency in promoting HDR-associated gene editing among them. Notably, entinostat treatment led to a significant increase in HDR-associated gene editing in vivo. Our study provides optimized HDAC inhibitor conditions for high-efficiency HDR-associated gene editing both in vivo and in vitro.

Background & Aims: Deletion of 15–21 nucleotides covering the preS1 start codon frequently occurs in patients with chronic HBV (CHB) with HBV genotype C and has been reported to be related to progression to hepatocellular carcinoma (HCC). However, the underlying mechanism causing the distinct phenotype of this HBV variant remains largely unknown. We investigated the mechanism by which preS1Del is related to liver disease progression and enhanced HBV replication, focusing on endoplasmic reticulum (ER) stress. Methods: The effects of HBV replicative capacity, ER stress signaling, inflammation, cell death, and tumorigenesis resulting from PreS1 deletions were investigated through in vitro and in vivo experiments. Inhibitors of the IRE1-JNK pathway and IL6 blockade were used to examine HCC tumor load induced by preS1 deletions. Results: The PreS1Del variant selectively activates the IRE1 pathway, mainly via enhanced colocalization between the ER and HBsAg in infected hepatocytes. This leads to enhanced HBV replication and production of tumor-promoting inflammatory cytokines and IL6 and COX2 via the IRE1-JNK signaling pathway. Furthermore, in vivo data showed that the activation of IRE1-JNK signaling consequently leads to lipid accumulation and apoptosis within 21Del-HBV-infected hepatocytes, collectively driving severe tumorigenesis in the liver. Notably, several inhibitors of the IRE1-JNK pathway dramatically inhibited HBV replication and inflammation induced by 21Del-HBV but not by the wild-type HBV in infected hepatocytes. Furthermore, IL6 blockade significantly reduced HCC tumor load induced by 21Del-HBV. Conclusions: PreS1Del leads to enhanced HBV replication and HCC development through IRE1-JNK-IL6/COX2-mediated hepatocyte proliferation and liver inflammation. Inhibitors interfering with the IRE1-JNK-IL6 pathway could selectively inhibit HBV replication and inflammation in preS1Dels, suggesting their potential for the treatment of patients with CHB with preS1-deleted HBV variants. Impact and implications:: Deletion of 15–21 nucleotides at the preS1 start codon is common in patients with CHB with HBV genotype C and is linked to HCC progression. However, the mechanisms underlying the distinct phenotype of this variant remain largely unknown. We found that the preS1Del variant selectively activates the IRE1 pathway, primarily through enhanced IRE1-JNK-IL6 signaling. Inhibition of either the IRE1-JNK pathway or IL6 reduced HBV replication and tumor load in in vivo HCC models. This study enhances our understanding of the mechanisms of liver disease progression caused by 5ʹ preS1Del variants and provides new insights into treatment strategies for patients with these variants. We believe our findings will resonate with a diverse audience, including patients and their physicians, the medical community, academia, the life sciences sector, and the general public.

Purpose: To study the treatment and outcomes of children with retinoblastoma (RB) with extraocular tumor extension (RB-EOE) and compare them with RB without extraocular tumor extension (RB-w/o-EOE). Design: Multicenter intercontinental collaborative prospective study from 2017 to 2020. RB-EOE cases included those with overt orbital tumor extension in treatment-naive patients. Cases with microscopic orbital extension detected postenucleation were excluded from the study. Participants: A total of 319 children with RB-EOE and 3116 children with RB-w/o-EOE. Intervention: Chemotherapy, enucleation, exenteration, radiotherapy. Main Outcome Measures: Systemic metastasis and death. Results: Of the 3435 RB patients included in this study, 309 (9%) were from low-income countries (LIC), 1448 (42%) from lower-middle income, 1012 (29%) from upper-middle income, and 666 (19%) patients from high-income countries. There was an inverse relationship between the percentage of RB-EOE and national income level, with 96 (31%) patients from LIC, 197 (6%) lower-middle income, 20 (2%) upper-middle income, and 6 (1%) patients from high-income countries (P = 0.0001). The outcomes were statistically significant for RB-EOE compared with RB-w/o-EOE: systemic metastasis (32% vs. 4% respectively; P = 0.0001) and metastasis-related death (63% vs. 6% respectively; P = 0.0001). Multimodal treatment was the most common form of treatment (n = 177; 54%) for RB-EOE, with most cases undergoing a combination of intravenous chemotherapy and enucleation (n = 97; 30%). Adjuvant external beam radiotherapy (EBRT) after surgery (enucleation/orbital exenteration) was given in only 68 (21%) cases. Kaplan–Meier analysis for systemic metastasis and metastasis-related death in RB-EOE was 28% and 57% at 1 year, 29% and 60% at 2 years, and 29% and 61% at 3 years, respectively. Cox regression analysis revealed that the risk of death from RB-EOE was greater in patients aged >4 years than

BackgroundDementia is a clinical syndrome characterized by a progressive decline in various cognitive domains. Since there is still no treatment for dementia, early diagnosis and prevention are the best approaches. In this context, the cognitive reserve (CR) concept has received considerable attention in dementia research with regard to prognosis. It originates from discrepancies between the degree of brain pathology and clinical manifestations. Acupuncture, as a complementary intervention, has long been widely applied in neurological diseases in East Asia. At the macroscale level, how acupuncture stimulation affects neural activity concerning CR in normal aging and dementia is largely unknown. ObjectiveThe aim of this study is to investigate the acute neural mechanisms of acupuncture stimulation concerning CR in the normal aging group and the group with cognitive impairment using neuroimaging methods. MethodsThis study is a randomized, placebo-controlled trial. Participants without (n=30) and with cognitive impairment (n=30) will be randomly assigned to the verum or sham acupuncture groups. The verum acupuncture group will receive acupuncture stimulation at acupoints related to cognitive function and gain deqi sensation. The sham acupuncture group will receive superficial needling at nonacupoints not related to cognitive function. Each group will undergo cognitive function tests, functional near-infrared spectroscopy imaging before and after acupuncture stimulation, and an assessment of CR. The primary outcomes will be differences in resting brain activities according to disease status, differences in resting brain connectivity before and after acupuncture stimulation between the 2 groups, and changes in brain activity in relation to the CR index. The secondary outcomes will be brain connectivity or network metrics associated with CR and differences in neural activity between the cognitive task and resting states. ResultsThe recruitment began in August 2023; to date, there have been 50 participants, divided into 20 in the group with cognitive impairment and 30 in the unimpaired group. The recruitment process will continue until February 2025. ConclusionsCR refers to the individual susceptibility to age-related brain changes and pathologies in cognitive impairment, and it is a factor affecting the trajectories of the disease. Although acupuncture is a widely used intervention for various neurological diseases, including dementia, its mechanism associated with CR at the macroscale has not been clearly identified. This study could contribute to identifying the neural mechanisms of acupuncture stimulation associated with CR using neuroimaging methods and provide a basis for future longitudinal research. Trial RegistrationClinical Research Information Service of the Republic of Korea KCT0008719; https://tinyurl.com/ydv5537n International Registered Report Identifier (IRRID)DERR1-10.2196/66838

This study aims to explore compositional changes of oligosaccharides, amino-type nitrogen, free amino acids volatile compounds, isoflavones, total phenol, total flavonoid, and antioxidant capacities during liquid-state fermentation (LSF) of soybean embryo homogenate (SEH) by Ganoderma lucidum to improve usability as functional food material. Raffinose and stachyose were almost completely hydrolyzed into monosaccharides such as fructose, glucose and galactose after 2 days of fermentation. After 5 days of fermentation, the contents of amino-type nitrogen and total free amino acids increased 7.0-fold and 2.4-fold, respectively, compared to the control group. Most of isoflavone glycosides were almost hydrolyzed into aglycones after 2 days and thereafter some of isoflavone aglycones were transformed into ortho-hydroxyisoflavones (OHIs). Total phenol, total flavonoid and antioxidants activities were significantly increased during the fermentation period. The result indicates that LSF of soybean embryo by G. lucidum can potentially improve acceptability and usability of soybean embryo as functional food material.

Fat-free yogurt often undergoes syneresis because it lacks fat. Although casein prevents syneresis, it induces protein aggregation and lumpy texture. Surfactants are commonly employed to mitigate these quality challenges. Saponins, abundant in Panax ginseng by-products like leaves and stems, possess surfactant activity, thereby preventing protein aggregation. In this study, ginseng leaf-stem extract (GE) was assessed to prevent lumpy and grainy yogurt texture. The fermentative, bioactive, physical, and sensory properties of GE-supplemented yogurt were evaluated. GE accelerated yogurt fermentation by promoting the growth of lactic acid bacteria and demonstrated higher antioxidant activity than unsupplemented yogurt. GE stabilized the yogurt matrix, and GE-supplemented yogurt exhibited smaller protein particles and reduced aggregation. Casein-induced lumpy texture was minimized by GE without compromising the syneresis-preventing ability of casein. Sensory evaluation confirmed the soft texture and acceptable taste of the GE-supplemented yogurt. Collectively, GE is a cost-effective surfactant option for improving the texture of fat-free yogurt.

Study region: The Ara Waterway, an artificial inland brackish waterway in South Korea. Study focus: This study investigates how water residence time and stratification affect water quality in an artificial brackish water system, which has different characteristics from natural environments and is under-researched, using numerical simulations. Various hydrodynamic conditions, including freshwater discharge and travel distances, were analyzed to understand their impact on residence times and stratification, offering insights for optimizing water quality management. New hydrological insights for the region: This study demonstrates that stratification significantly impacts water quality more than residence time in artificial brackish waterways. In contrast to lakes or reservoirs, increasing freshwater discharge in artificial brackish waterways can enhance stratification, reducing vertical mixing and degrading water quality, especially in the bottom layers. In the F0 scenario, excluding freshwater inflow increased summer maximum dissolved oxygen by 1.37 times compared to the validation case. This suggests that breaking stratification, such as through underwater aeration systems, may be more effective than focusing on residence time. In the L15 scenario, with the longest travel distance, upstream total nitrogen and total phosphorus increased by 18.37 % and 26.12 %, while downstream levels decreased by 3.35 % and 10.52 %. Additionally, poorer quality freshwater can degrade overall water quality, even with shorter residence times. These findings emphasize the need for careful management of inflowing water to maintain water quality in artificial brackish waterways.

Summary: The human body reacts to tissue damage by generating damage-associated molecular patterns (DAMPs) that activate sterile immune responses. To date, little is known about how DAMPs are removed to avoid excessive immune responses. Here, we show that proteasomal dysfunction induces the release of mitochondrial DNA (mtDNA) as a DAMP that activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway and is subsequently degraded through the N-degron pathway. In the resolution phase of sterile immune responses, DNA-dependent protein kinase (DNA-PK) senses cytosolic mtDNA and activates N-terminal (Nt-) arginylation by ATE1 R-transferases. The substrates of Nt-arginylation include the molecular chaperone BiP/GRP78 retrotranslocated from the endoplasmic reticulum (ER). R-BiP, the Nt-arginylated species of BiP, is associated with cytosolic mtDNA to accelerate its targeting to autophagic membranes for lysosomal degradation. Thus, cytosolic mtDNA activates the N-degron pathway to facilitate its own degradation and form a negative feedback loop, by which the cell can turn off sterile immune responses at the right time.

IntroductionAn effective vaccination policy must be implemented to prevent foot-and-mouth disease (FMD). However, the currently used vaccines for FMD have several limitations, including induction of humoral rather than cellular immune responses.MethodsTo overcome these shortcomings, we assessed the efficacy of levamisole, a small-molecule immunomodulator, as an adjuvant for the FMD vaccine. We conducted in vitro studies using murine peritoneal exudate cells (PECs) and porcine peripheral blood mononuclear cells (PBMCs) and in vivo studies using mice (experimental animals) and pigs (target animals). We evaluated levamisole-mediated modulation of the innate and adaptive immune responses; early, mid-term, and long-term immune-inducing effects; modes of action; and host defense against viral infection.ResultsLevamisole treatment promoted IFNγ secretion in murine PECs and porcine PBMCs. Additionally, it induced robust and long-lasting immune responses by eliciting high antibody titers and high virus-neutralizing antibody titers. By activating downstream signaling pathways of various pattern-recognition receptors, levamisole stimulated the expression of multiple cytokines and costimulatory molecules. Owing to these immunostimulatory effects, levamisole elicited host defense against viral infections in pigs. Our findings demonstrate the potential of levamisole as an immunostimulatory agent.DiscussionThe results also indicate that levamisole, as an adjuvant for animal vaccines, can elicit robust innate and adaptive immune responses, thereby enhancing host defense against viral infections. This study provides a promising approach for the development of improved FMD vaccine strategies in the future.

In this study, we examine the volatilization of oxygen in titanium under electron beam melting (EBM) conditions, correlating the beam output with oxygen content changes. The potential for titanium deoxidation through the application of electron beams remains a subject of ongoing debate. To verify this experimentally, the effects of electron beam processing on the oxygen contents of different titanium raw materials are quantified by nitrogen/oxygen analysis. Moreover, the mechanism of oxygen diffusion in titanium, which is affected by the positively charged surface layer generated by the electron beam, is evaluated by determining the corresponding activation energy using density functional theory (DFT) calculations. An average reduction of oxygen concentration by 50 % was observed following EBM. Residual gas analysis confirmed the evolution of oxygen gas over a duration of 10 min. Thermodynamic calculations indicate that deoxidation is feasible at temperatures exceeding 4,000 K in a vacuum of approximately 5 × 10−7 Torr, thereby substantiating the potential for deoxidation. Furthermore, DFT calculations demonstrated that the oxygen diffusion coefficient increases proportionally with an increase in positive surface charge, thereby facilitating the removal of oxygen in an electron beam environment.

Recent safety issues such as cladding oxidation and fuel fragmentation, relocation and dispersal (FFRD) make the loss-of-coolant accident (LOCA) acceptance criteria more difficult to be satisfied. To obtain the adequate safety margin and more economical use of the nuclear power plant, re-classification of LOCAs for Korean operating PWRs is now under consideration to exclude the large break LOCA (LBLOCA) from the design basis accidents (DBAs). Therefore, the intermediate break LOCA (IBLOCA) might become the limiting break size of concern in the LOCA analysis. To accomplish this reform of LOCA classification, an extensive understanding of IBLOCA is crucial, and the applicability of safety analysis code should be confirmed. For this purpose, IBLOCA PIRT was developed. The PIRT panel was organized and the general process of the PIRT development established by Wilson and Boyack (1998) was adopted to develop the IBLOCA PIRT. Based on IBLOCA analyses using the safety and performance analyzing code (SPACE), the PIRT panel defined the temporal phases, systems, components and possible phenomena during an IBLOCA. For all possible phenomena, the relative importance and the knowledge level were determined for each component and each phase via discussions among PIRT panel members. For phenomena having relatively high importance, a code validation matrix was also developed. The results of the IBLOCA PIRT will be used to improve the SPACE code for IBLOCA application and resolve future regulatory issues.

Medial elbow pain is a common musculoskeletal problem among individuals engaging in repetitive activities. Medial epicondylitis is the predominant cause of this pain. However, other potential causes must be considered as part of the differential diagnosis. This article discusses several etiologies of medial elbow pain, including medial epicondylitis, ulnar neuropathy, snapping triceps syndrome, ulnar collateral ligament injury, medial antebrachial cutaneous neuropathy, and diseases of the elbow joint, with an emphasis on ultrasound (US) findings. Awareness of possible diagnoses and their US features can assist radiologists in establishing a comprehensive diagnosis for medial elbow pain.

Abstract Background Physical fitness is considered an important indicator of the health of the general public. In particular, the physical fitness of the older adults is an important requirement for determining the possibility of independent living. Therefore, the purpose of this study was to examine the association between chronological age and physical fitness variables in the National Fitness Award Cohort study data and to develop multiple linear regression analyses to predict fitness age using dependent variables. Methods Data from 501,774 (359,303 adults, 142,471 older adults) individuals who participated in the Korea National Fitness Award Cohort Study from 2017 to 2021 were used. The physical fitness tests consisted of 5 candidate markers for adults and 6 candidate markers for the older adults to measure muscle strength, muscle endurance, cardiopulmonary endurance, flexibility, balance, and agility. Pearson’s correlation and stepwise regression analyses were used to analyze the data. Results We obtained a predicted individual fitness age values from physical fitness indicators for adults and older adults individuals, and the mean explanatory power of the fitness age for adults was [100.882 – (0.029 × VO2max) – (1.171 × Relative Grip Strength) – (0.032 × Sit-up) + (0.032 × Sit and reach) + (0.769 × Sex male = 1; female = 2)] was 93.6% (adjusted R2); additionally, the fitness age for older adults individuals was [79.807 – (0.017 × 2-min step test) – (0.203 × Grip Strength) – (0.031 × 30-s chair stand) – (0.052 × Sit and reach) + (0.985 × TUG) – (3.468 × Sex male = 1; female = 2) was 24.3% (adjusted R2). Conclusions We suggest the use of fitness age as a valid indicator of fitness in adults and older adults as well as a useful motivational tool for undertaking exercise prescription programs along with exercise recommendations at the national level.

Pancreatic cancer is usually detected through contrast-enhanced CT and MRI. However, pancreatic cancer is occasionally overlooked because of its small size or is misdiagnosed as other conditions due to atypical imaging features that present diagnostic challenges. Considering the rapid growth and poor prognosis associated with pancreatic cancer, the ability to accurately detect and differentiate pancreatic lesions is crucial for appropriate surgical intervention. Reviewing diverse challenging cases of pancreatic cancer at an early stage and other mimicking lesions may help us accurately interpret the imaging features of pancreatic cancer on CT and MRI scans. Therefore, we aimed to illustrate various imaging features of pancreatic cancer and its mimicking lesions and provide valuable insights for differential diagnosis.

We present a case of iatrogenic iliac vein rupture with venous thrombosis during total hip arthroplasty that was endovascularly treated with the insertion of covered and uncovered stents, aspiration, and balloon maceration of the thrombus. We describe in detail, with a schematic diagram, an endovascular treatment method that can be performed under local anesthesia alone and explain how to overcome the situation when the diameter of the covered stent is inadequate to cover the iliac vein.