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Abstract In four dimensions, ’t Hooft symbols offer a compact and powerful framework for describing the self-dual structures fundamental to instanton physics. Extending this to six dimensions, the six-dimensional ’t Hooft symbols can be constructed using the isomorphism between the Lorentz group Spin(6) and the unitary group SU(4). We demonstrate that the six-dimensional self-dual structures governed by the Hermitian Yang-Mills equations can be elegantly organized using these generalized ’t Hooft symbols. We also present a systematic method for constructing Hermitian Yang-Mills instantons from spin connections on six-dimensional manifolds using the generalized ’t Hooft symbols. We provide a thorough analysis of the topological invariants such as instanton and Euler numbers.

Abstract Background Tongue necrosis is a rare and relatively uncommon condition, usually caused by vasculitis, thrombosis, severe hypotension due to septic or cardiogenic shock, vasopressor use, or intubation. Following damage such as necrosis, dystrophic calcification, a type of soft tissue calcification, can occur. Case presentation: Herein, we present a unique case of bilateral tongue necrosis in a patient with nonintubated septic shock. A 70-year-old East Asian man with no significant medical history presented to the emergency department with postprandial epigastric pain. The patient was admitted to the intensive care unit with hypotension due to septic shock and disseminated intravascular coagulation. After a short course of vasopressors, the patient developed tongue discoloration and swelling without limb ischemia. Computed tomography was performed to observe the tongue necrosis, and calcification of the tongue was found. The patient was successfully treated by wiping the area with a hexamidine-soaked gauze. Conclusion Tongue necrosis remains a rare finding, and its occurrence as a complication of vasopressor use is even rarer. Therefore, even with relatively short courses of vasopressors in the intensive care unit, daily visualization of the tongue to check for discoloration, along with daily inspection and pulse checks of the limbs, can help identify vasospasms. These measures allow for prompt intervention, minimizing permanent damage and shortening the recovery time.

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic condition characterized by relapsing and remitting inflammation of the gastrointestinal tract. The pathogenesis involves a complex interplay of genetic, environmental, and immune factors. Treatment paradigms have evolved significantly over the past few decades, with the introduction of biologics, particularly anti-TNF (tumor necrosis factor) agents, marking a significant advancement. Anti-TNF therapies, including infliximab, adalimumab, golimumab, and certolizumab pegol, have efficacy in inducing and maintaining remission, promoting mucosal healing, and improving the quality of life in moderate to severe IBD patients. The early and appropriate use of these agents can mitigate disease progression and reduce the dependency on corticosteroids, enhancing long-term patient outcomes. Nevertheless, these therapies are expensive and are associated with potential adverse effects, including increased risk of infections and malignancies. This review discusses the mechanisms, clinical efficacy, safety profiles, and therapeutic positioning of anti-TNF agents in IBD management, integrating current Korean treatment guidelines.

Abstract Auxetic metamaterials are a unique class of materials or structures with a negative Poisson’s ratio and a wide array of functionalities. However, their inherent porosity presents challenges in practical applications. Filling the inherent perforations while preserving their unique auxeticity is difficult because it demands the seamless integration of components that have highly distinct mechanical characteristics. Here we introduce a seamless auxetic substrate film capable of achieving a negative Poisson’s ratio of −1, the theoretical limit of isotropic materials. This breakthrough is realized by incorporating a highly rigid auxetic structure reinforced by glass-fabric, with surface-flattening soft elastomers. We effectively optimize the mechanical properties of these components by systematic experimental and theoretical investigations into the effects of relative differences in the moduli of the constituents. Using the developed auxetic film we demonstrate an image distortion-free display having 25 PPI resolution of micro-LEDs that is capable of 25% stretching without performance degradation.

Purpose We aimed to evaluate whether pediatric emergency practice has improved since the introduction of pediatric specialist care (PSC). Methods Retrospective observational study was conducted using the data retrieved from the emergency department (ED) of a tertiary university hospital in Cheongju, Korea. Patients younger than 19 years who visited the ED from January 2019 through December 2023 were enrolled in this study. Hospitalization (overall and intensive care unit [ICU]), in-hospital mortality, and return visit within 24 hours were compared between the periods before (January 2019-January 2021) and after (June 2021-December 2023) the introduction of PSC. Adjusted odds ratios with 95% confidence intervals were calculated for the outcomes using multivariable logistic regression. Results During the study period, a total of 36,162 patients visited the ED. The visits increased from 12,196 before to 22,387 after the introduction of PSC (increase by 83.6%). Annual numbers of the visits have increased since 2020 and reached 10,942 in 2023. After the introduction of PSC, decreases were noted in the hospitalization (adjusted odds ratio, 0.67; 95% confidence interval, 0.62-0.72) and return visit within 24 hours (0.73; 0.61-0.88). Hospitalization to the ICU increased (2.90; 2.29-3.69), while there was no significant difference in the in-hospital mortality (1.31; 0.77-2.25). Conclusion After the introduction of PSC, overall hospitalization and return visit decreased, while hospitalization to the ICU increased without a difference in the in-hospital mortality. Multidisciplinary efforts are needed to continue providing the pediatric specialist-centered emergency practice.

Inverse design of metamaterial structures with customized strain-dependent Poisson’s ratio has significant potential across various applications. However, achieving precise control over these mechanical properties presents a challenge due to the complex relationship between geometry and mechanical performance. Here, we present a novel data-driven approach utilizing a constrained generative inverse design network (CGIDN) to address this challenge. The CGIDN uses backpropagation to efficiently navigate the design space and achieve target mechanical properties with high accuracy. Our method starts by generating a comprehensive dataset of Poisson’s ratio-strain curves for various geometries incorporating cuts. These curves are then compressed using principal component analysis (PCA) to reduce dimensionality while preserving essential features. A deep neural network (DNN) is then trained to map input geometric parameters to these principal components, with the architecture optimized using grid search. The CGIDN facilitates the inverse design process by recommending geometric parameters for unit cell designs that match specified target Poisson’s ratio-strain curves. We validated the effectiveness of our approach through Finite Element Analysis (FEA) and experimental verification. The FEA results for the designed unit cells showed high agreement with the target and predicted curves, demonstrating the accuracy of the CGIDN model. Further, tensile tests on specimens confirmed that the inverse-designed structures reproduced the desired mechanical behavior upon scale-up. Our method, which enables efficient and accurate design of metamaterials with tailored mechanical properties, holds promise for applications in wearable devices, soft robotics, and advanced sensor systems.

Background Little is known about alterations of the rotator cuff (RC) macroscopic vasculature associated with medical conditions and/or habits that predispose a person to diseases of the peripheral microcirculation. The high frequency of cuff tear and re-tear in patients with diabetes, hypercholesterolemia, uncontrolled arterial hypertension, or metabolic syndrome may be due to tissue hypovascularity. Methods The macroscopic vasculature of both the articular and bursal sides of the posterosuperior RC was evaluated arthroscopically in 107 patients (mean age, 58.2 years) with no RC tear. Patients were divided into three groups according to medical comorbidities and lifestyle factors (group I, none; group II, smokers and/or drinkers and one comorbidity; and group III, two or more comorbidities). Pulsating vessels originating from both the myotendinous and osteotendinous junctions were assessed as “clearly evident,” “poorly evident,” or “not evident.” Results Groups I, II, and III comprised 36, 45, and 26 patients, respectively. Within the myotendinous junction, vessels were visualized in 22 group I patients (61%), 25 group II patients (55%), and 6 group III patients (23%) (P=0.007). Pulsating arterial vessels originating from the osteotendinous junction were seen in 42%, 36%, and 0% of patients, respectively (P

Abstract Spinal cord injury (SCI) leads to motor and sensory impairment below the site of injury, thereby necessitating rehabilitation. An enriched environment (EE) increases social interaction and locomotor activity in a mouse model, similar to human rehabilitation. However, the impact of EE on presynaptic plasticity in gene expression levels remains unclear. Hence, this study aimed to investigate the therapeutic potential of EE in an SCI mouse model. Mice with spinal cord contusion were divided into two groups: those housed in standard cages (control) and those in EE conditions (EE). Each group was housed separately for either 2- or 8-weeks post-injury, after which RNA sequencing was performed and compared to a sham group (receiving only a dorsal laminectomy). The synaptic vesicle cycle (SVC) pathway and related genes showed significant downregulation after SCI at both time points. Subsequently, we investigated whether exposure to EE for 2- and 8-weeks post-SCI could modulate the SVC pathway and its related genes. Notably, exposure to EE for 8 weeks resulted in a marked reversal effect of SVC-related gene expression, along with stimulation of axon regeneration and mitigation of locomotor activity loss. Thus, prolonged exposure to EE increased presynaptic activity, fostering axon regeneration and functional improvement by modulating the SVC in the SCI mouse model. These findings suggest that EE exposure proves effective in inducing activity-dependent plasticity, offering a promising therapeutic approach akin to rehabilitation training in patients with SCI.

Background/Aims A poor prognostic factor for Crohn’s disease (CD) includes perianal fistulizing disease, including perianal fistula and/or perianal abscess. Currently, a tool to assess perianal symptoms in patients with CD remains nonexistent. This study aimed to develop a perianal fistulizing disease self-screening questionnaire for patients with CD. Methods This prospective pilot study was conducted at three tertiary referral centers between January 2019 and May 2020. We formulated questions on perianal symptoms, including tenesmus, anal discharge, bleeding, pain, and heat. A 4-point Likert scale was used to rate each question. Patients with CD completed a questionnaire and underwent pelvic magnetic resonance imaging (MRI). Results Overall, 93 patients were enrolled, with 51 (54.8%) diagnosed with perianal fistulizing disease, as determined by pelvic MRI. The Spearman correlation findings demonstrated that anal pain (p = 0.450, p < 0.001) and anal discharge (p = 0.556, p < 0.001) were the symptoms that most significantly correlated with perianal disease. For anal pain and discharge, the area under the receiver operating characteristic curve of the scores was significantly higher than that of the combined score for all five symptoms (0.855 vs. 0.794, DeLong’s test p = 0.04). For the two symptoms combined, the sensitivity, specificity, and positive predictive and negative predictive values were 88.2, 73.8, 80.4, and 83.8%, respectively, with 81.7% accuracy for detecting perianal fistulizing disease. Conclusions This study indicates that simple questions regarding anal pain and discharge can help accurately identify the presence of perianal fistulizing disease in patients with CD.

Abstract We aimed to determine whether Crohn’s disease (CD) activity patterns assessed via a web-based symptom diary can help predict clinical outcomes in patients with newly diagnosed CD. Patients diagnosed with CD within the preceding 3 months were prospectively enrolled at four tertiary centers. All patients recorded their symptoms on a website using a smartphone at least once a week. The index outcomes were disease-related admission and surgery during follow-up. The disease activity from enrollment to outcome or last follow-up was reviewed for pattern analysis. Cox regression analysis was used to identify the predictors of disease outcomes. A total of 102 patients were enrolled. During a median follow-up period of 42 months, 25 (24.5%) and 6 (5.9%) patients required admission and surgery, respectively. Poor activity pattern was an independent predictor of disease-related hospitalization (adjusted hazard ratio [aHR], 3.96; 95% confidence interval [CI] 1.5–10.45; p = 0.005). A poor activity pattern (aHR, 19.48; 95% CI 1.86–203.95; p = 0.013) and female sex (aHR, 11.28; 95% CI 1.49–85.01; p = 0.018) were found to be independent predictors of bowel resection. CD disease activity patterns monitored through the mobile monitoring system may help predict clinical outcomes, such as disease-related hospitalization and surgery, in patients with newly diagnosed CD.

Abstract Background Oral ulcers are a common side effect of chemotherapy and affect patients’ quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness. Methods Animals were divided into four experimental groups: Control, TMC hydrogel, hTMSCs, and hTMSCs loaded in TMC hydrogel (Hydrogel + hTMSCs) (each n = 8). Oral ulcers were chemically induced by anesthetizing the rats followed by injection of dilute acetic acid in the right buccal mucosa. After confirming the presence of oral ulcers in the animals, a single subcutaneous injection of 100 µL of each treatment was applied to the ulcer area. Histological analyses were performed to measure inflammatory cells, oral mucosal thickness, and fibrosis levels. The expression level of inflammatory cytokines was also measured using RT-PCR to gauge therapeutic the effect. Results The ulcer size was significantly reduced in the TMC hydrogel + hTMSCs group compared to the control group. The stem cells in the tissue were only observed until Day 3 in the hTMSCs treated group, while the injected stem cells in the TMC Hydrogel + hTMSCs group were still present until day 7. Cytokine analysis related to the inflammatory response in the tissue confirmed that the TMC Hydrogel + hTMSCs treated group demonstrated superior wound healing compared to other experimental groups. Conclusion This study has shown that the adhesion and viability of current stem cell therapies can be resolved by utilizing a hydrogel prepared with TMC and combining it with hTMSCs. The combined treatment can promote rapid healing of oral cavity wounds by enhancing anti-inflammatory effects and expediting wound healing. Therefore, hTMSC loaded in TMC hydrogel was the most effective wound-healing approach among all four treatment groups prolonging stem cell survival. However, further research is necessary to minimize the initial inflammatory response of biomaterials and assess the safety and long-term effects for potential clinical applications.

Introduction: Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) improves bystander CPR rates and survival outcomes. This study aimed to identify barriers to successful DA-CPR in patients with out-of-hospital cardiac arrest (OHCA). Methods: This retrospective observational study used data from a nationwide OHCA database from 2017 to 2021. Adult emergency medical services (EMS)-treated patients with OHCA with a presumed cardiac etiology were enrolled. The main exposure variable was compliance with DA-CPR. The primary outcome was good neurological recovery at hospital discharge. Multivariable logistic regression analysis was conducted to identify the major factors associated with unsuccessful DA-CPR with and without multiple imputations. Causal mediation analysis was conducted using witnessed status as a mediator. Results: In the final analysis, 49,165 patients with OHCA were included. A total of 36,865 (75.0%) patients successfully underwent DA-CPR. A higher proportion of good neurological recovery was observed in the successful DA-CPR group than in the non-successful DA-CPR group (P 65 years, male sex, OHCA occurring in a non-metropolitan area or private place, unwitnessed status, whether the bystander was a non-family member or non-cohabitant, female sex or had not received CPR training, and primary call dispatchers not receiving any first-aid training. Additional analyses after multiple imputations showed similar results. Mediation effect was significant for most risk factors for unsuccessful DA-CPR. Conclusions: Bystander characteristics (non-family member or non-cohabitant, female, and uneducated status for CPR) and primary call dispatchers not receiving first-aid training were identified as risk factors for unsuccessful DA-CPR.

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

Abstract CRISPR/Cas9 technology has effectively targeted cancer-specific oncogenic hotspot mutations or insertion–deletions. However, their limited prevalence in tumors restricts their application. We propose a novel approach targeting passenger single nucleotide variants (SNVs) in haploinsufficient or essential genes to broaden therapeutic options. By disrupting haploinsufficient or essential genes through the cleavage of DNA in the SNV region using CRISPR/Cas9, we achieved the selective elimination of cancer cells without affecting normal cells. We found that, on average, 44.8% of solid cancer patients are eligible for our approach, a substantial increase compared to the 14.4% of patients with CRISPR/Cas9-applicable oncogenic hotspot mutations. Through in vitro and in vivo experiments, we validated our strategy by targeting a passenger mutation in the essential ribosomal gene RRP9 and haploinsufficient gene SMG6. This demonstrates the potential of our strategy to selectively eliminate cancer cells and expand therapeutic opportunities.

Abstract Multisensory integration is necessary for the animal to survive in the real world. While conventional methods have been extensively used to investigate the multisensory integration process in various brain areas, its long-range interactions remain less explored. In this study, our goal was to investigate interactions between visual and somatosensory networks on a whole-brain scale using 15.2-T BOLD fMRI. We compared unimodal to bimodal BOLD fMRI responses and dissected potential cross-modal pathways with silencing of primary visual cortex (V1) by optogenetic stimulation of local GABAergic neurons. Our data showed that the influence of visual stimulus on whisker activity is higher than the influence of whisker stimulus on visual activity. Optogenetic silencing of V1 revealed that visual information is conveyed to whisker processing via both V1 and non-V1 pathways. The first-order ventral posteromedial thalamic nucleus (VPM) was functionally affected by non-V1 sources, while the higher-order posterior medial thalamic nucleus (POm) was predominantly modulated by V1 but not non-V1 inputs. The primary somatosensory barrel field (S1BF) was influenced by both V1 and non-V1 inputs. These observations provide valuable insights for into the integration of whisker and visual sensory information.

Background/Aims Mucoprotective agents, such as eupatilin, are often prescribed to prevent gastrointestinal (GI) bleeding in addition to an acid suppressant despite the absence of a large-scale study. We evaluated the additional effect of eupatilin on the prevention of GI bleeding in both the upper and lower GI tract in concomitant aspirin and acid suppressant users using the nationwide database of national claims data from the Korean National Health Insurance Service (NHIS). Methods An aspirin cohort was constructed using the NHIS claims data from 2013 to 2020. Patients who manifested with hematemesis, melena, or hematochezia were considered to have GI bleeding. A Cox proportional hazards regression model was used to determine the risk factors for GI bleeding associated with the concomitant use of GI drugs and other covariates among aspirin users. Results Overall, a total of 432,208 aspirin users were included. The concurrent use of an acid suppressant and eupatilin (hazard ratio [HR] = 0.85, p = 0.016, vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Moreover, a more than 3-month duration (HR = 0.88, p = 0.030) of acid suppressant and eupatilin prescription (vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Conclusions Eupatilin administration for ≥ 3 months showed additional preventive effect on GI bleeding in concomitant aspirin and acid suppressant users. Thus, cotreatment with eupatilin with a duration of 3 months or longer is recommended for reducing GI bleeding among aspirin plus acid suppressant users.

Background/Aims Long-term use of acid suppressants such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonist (H2RA) has been associated with the risk of osteoporotic fracture. Acid suppressants and muco-protective agents (MPAs) are often used together as anti-ulcer agents. We evaluated the association between the risk of osteoporotic fracture and the combined use of these anti-peptic agents. Methods A population-based case-control study was conducted by analyzing the Korean National Health Insurance Data from 2014 to 2020. Patients who had been prescribed anti-peptic agents, such as PPI, H2RA, or MPA, were included. Considering the incidence of osteoporotic fractures, the case group (n = 14,704) and control group (n = 58,816) were classified by 1:4 matching based on age and sex. Results The use of all types of anti-peptic agents was associated with an increased risk of osteoporotic fractures (PPI: hazard ratio [HR], 1.31; H2RA: HR, 1.44; and MPA: HR, 1.33; all p < 0.001). Compared to PPI alone, the combined use of “PPI and H2RA” (HR, 1.58; p = 0.010) as well as “PPI, H2RA, and MPA” (HR, 1.71; p = 0.001) was associated with an increased risk of osteoporotic fracture. However, compared with PPI alone, “MPA and PPI or H2RA” was not associated with an increased risk of osteoporotic fracture. Conclusions This study found that the combined use of “PPI and H2RA” was associated with a higher risk of osteoporotic fractures. In cases where deemed necessary, the physicians may initially consider prescribing the combination use of MPA.

Abstract Background and purpose The ANNEXA‐4 trial measured hemostatic efficacy of andexanet alfa in patients with major bleeding taking factor Xa inhibitors. A proportion of this was traumatic and nontraumatic intracranial bleeding. Different measurements were applied in the trial including volumetrics to assess for intracranial bleeding depending on the compartment involved. We aimed to determine the most reliable way to measure intracranial hemorrhage (ICrH) volume by comparing individual brain compartment and total ICrH volume. Methods Thirty patients were randomly selected from the ANNEXA‐4 database to assess measurement of ICrH volume by compartment and in total. Total and compartmental hemorrhage volumes were measured by five readers using Quantomo software. Each reader measured baseline hemorrhage volumes twice separated by 1 week. Twenty‐eight different ANNEXA‐4 subjects were also randomly selected to assess intra‐rater reliability of total ICrH volume measurement change at baseline and 12‐h follow up, performed by three readers twice to assess hemostatic efficacy categories used in ANNEXA‐4. Results Compartmental minimal detectable change percentages (MDC%) ranged between 9.72 and 224.13, with the greatest measurement error occurring in patients with a subdural hemorrhage. Total ICrH volume measurements had the lowest MDC%, which ranged between 6.57 and 33.52 depending on the reader. Conclusion Measurement of total ICrH volumes is more accurate than volume by compartment with less measurement error. Determination of hemostatic efficacy was consistent across readers, and within the same reader, as well as when compared to consensus read. Volumetric analysis of intracranial hemostatic efficacy is feasible and reliable when using total ICrH volumes.

Background A precontoured plate rarely fits properly within the patient’s clavicle and must be bent intraoperatively. This study aimed to determine whether anatomical reduction could be achieved using a plate bent before surgery. Methods This study included 87 consecutive patients with displaced mid-shaft clavicle fractures who underwent plate fixation and were followed-up for a minimum of 1 year. After exclusions, 39 consecutive patients underwent fixation with a precontoured plate bent intraoperatively (intraoperative bending group), and 28 underwent fixation with the plate bent preoperatively (preoperative bending group). Using free software and a three-dimensional (3D) printer, ipsilateral clavicle 3D-printed models were constructed. Using plain radiographs, the distance between the edge of the lateral inferior cortex and the medial inferior cortex was measured. The angle between the line connecting the inferior cortex edge and the line passing through the flat portion of the superior cortex of the distal clavicle was measured. Results Mean length differences between the ipsilateral and contralateral clavicle were smaller on both anteroposterior (AP; P=0.032) and axial images (P=0.029) in the preoperative bending group. The mean angular differences on both AP (P=0.045) and axial images (P=0.008) were smaller in the preoperative bending group. No significant differences were observed between the two groups in functional scores at the last follow-up. Conclusions Smaller differences in length and angle between the ipsilateral and contralateral clavicle, indicative of reduction, were observed in the preoperative bending group. Using the prebending technique with low expense, the operation was performed more effectively as reflected by a shorter operation time. Level of evidenceIII.

Abstract It was shown that Yang-Mills instantons on an internal space can trigger the expansion of our four-dimensional universe as well as the dynamical compactification of the internal space. We generalize the instanton-induced inflation and dynamical compactification to general Einstein manifolds with positive curvature and also to the FLRW metric with spatial curvature. We explicitly construct Yang-Mills instantons on all Einstein manifolds under consideration and find that the homogeneous and isotropic universe is allowed only if the internal space is homogeneous. We then consider the FLRW metric with spatial curvature as a solution of the eight-dimensional Einstein-Yang-Mills theory. We find that open universe (k = −1) admits bouncing solutions unlike the other cases (k = 0, +1).

Adrenal gland trauma is uncommon and is diagnosed at an increasing frequency using CT scans. However, owing to the rarity of this injury and its diverse clinical presentations and prognoses, there is no consensus on its management. In this case report, a 73-year-old male patient experienced recurrent bleeding in the right adrenal gland due to an in-car traffic accident, which was treated with repeated transcatheter arterial embolization.

Abstract The Pacific abalone (Haliotis discus hannai) is the most economically valuable shellfish species in Northeast Asia, accounting for most of the shellfish production in South Korea. Despite the continuous improvement in the productivity of domestic abalone aquaculture, rapid seawater temperature changes caused by global warming have led to mass mortality in coastal abalone farms. Therefore, research on environmental stressors is urgently needed to prevent abalone production losses. This study analyzed the expression of heat shock protein (HSP) genes in foot muscles of H. discus hannai and metabolic parameters including glucose, lysozyme, catalase, D‐lactate, and trehalose levels in the hemolymph under acute high temperature, low temperature, low salinity, and air exposure. Quantitative reverse‐transcription polymerase chain reaction analysis showed that HSP20 expression was downregulated in all experimental groups, whereas HSP70 expression increased immediately in all experimental groups except for the low‐temperature stress group. Hemolymph analysis showed that glucose and lysozyme levels increased significantly immediately after treatment in all groups, and decreased during the recovery period. Together, the results indicate that low water temperature stress had the smallest effect on abalone among the treatments. We conclude that the other treatments acted as stressors of abalone and that HSP genes, glucose, and lysozyme can be used as stress indicators in H. discus hannai.

The effects of aging on the healing capacity of maxillofacial bone defects have not been studied. The aim of this study was to evaluate the effects of aging on the regeneration of round bony defects in the mandible. We created a round-shaped bony defect in the mandibular angle area in rats of different ages (2-[2 M], 10-[10 M], and 20-month-old [20 M]) and evaluated new bone regeneration in these groups. Changes in bone turnover markers such as alkaline phosphatase, procollagen type I N-terminal propeptide (PINP), cross-linked C-telopeptide of type I collagen, and tartrate-resistant acid phosphatase 5B (TRAP5b) were investigated. The bone volume/total volume and bone mineral density of the 20 M group were significantly higher than those of the 2 M group (p = 0.029, 0.019). A low level of the bone formation marker PINP was observed in the 20 M group, and a high level of the bone resorption marker TRAP5b was observed in the 10 M and 20 M groups. Micro-computed tomography (µ-CT) results showed that older rats had significantly higher bone formation than younger rats, with lower serum levels of PINP and higher levels of TRAP5b. The local environment of the old rat bone defects, surrounded by thickened bone, may have affected the results of our study. In conclusion, old rats showed greater new bone regeneration and healing capacity for round mandibular bone defects. This result was related to the fact that the bone defects in the 20 M rat group provided more favorable conditions for new bone regeneration.

The human clavicle’s unique S-shaped, three-dimensional structure complicates fracture management. This study evaluated the anatomical conformity of pre-contoured anatomical plates using 3D-printed clavicle models. CT scans from 30 patients (15 males and 15 females) were used to create these models. Three brands of distal clavicle plate systems (Acumed, Synthes, and Arthrex) were tested for fit. Measurements included the distance from the distal end of the clavicle to the plate’s lateral end, the gap between the clavicle and the plate, and the overhang distance. Results showed significant differences in clavicle length between sexes, with men having a mean length of 156.1 ± 7.6 mm and women 138.4 ± 4.3 mm, both with normal distribution (p > 0.05). The mean lateral distance was 7.9 ± 1.7 mm, and the mean medial gap was 3.6 ± 3.0 mm, showing no significant differences between products or sexes. The mean overhang distance was 5.8 ± 4.6 mm, with larger values in women for the Acumed (p = 0.037) and Arthrex (p = 0.000) plates. Overall, pre-contoured plates exhibited notable discrepancies, especially in shorter clavicles.

Purpose To investigate whether CT-based tumor regression grade (ctTRG) can be used to predict the response to neoadjuvant chemotherapy (NAC) in colon cancer. Materials and Methods A total of 53 patients were enrolled. Two radiologists independently assessed the ctTRG using the length, thickness, layer pattern, and luminal and extraluminal appearance of the tumor. Changes in tumor volume were also analyzed using the 3D Slicer software. We evaluated the association between pathologic TRG (pTRG) and ctTRG. Patients with Rödel’s TRG of 2, 3, or 4 were classified as responders. In terms of predicting responder and pathologic complete remission (pCR), receiver operating characteristic was compared between ctTRG and tumor volume change. Results There was a moderate correlation between ctTRG and pTRG (ρ = -0.540, p < 0.001), and the interobserver agreement was substantial (weighted к = 0.672). In the prediction of responder, there was no significant difference between ctTRG and volumetry (Az = 0.749, criterion: ctTRG ≤ 3 for ct- TRG, Az = 0.794, criterion: ≤ -27.1% for volume, p = 0.53). Moreover, there was no significant difference between the two methods in predicting pCR (p = 0.447). Conclusion ctTRG might predict the response to NAC in colon cancer. The diagnostic performance of ctTRG was comparable to that of CT volumetry.

Common carotid artery occlusion (CCAO) is a very rare disorder that has rarely been studied. CCAO causes several neurological symptoms but can sometimes be asymptomatic due to the development of various anastomoses. Herein, we report the case of a 70-year-old male patient diagnosed with asymptomatic CCAO due to anastomotic flow. The patient underwent transfemoral cerebral angiography (TFCA) and was found to have CCAO with two collateral pathways, including an occipital arteryvertebral artery anastomosis. We emphasize the importance of TFCA when CCAO is suspected and review the types and anastomotic pathways of CCAO.

Rotator cuff tear is a common shoulder injury that compromises both function and quality of life. Despite the prevalence of the injury and advancements in repair techniques, a significant percentage of these repairs fail. This review aims to explore the multifactorial reasons behind this failure, including the degenerative nature of the rotator cuff tendon, inherent and extrinsic factors, and the role of hypoxia in tissue degeneration. Additionally, it elucidates potential strategies for improving healing outcomes.

Background/Aims: Low-volume preparations for colonoscopy are gaining attention for their higher acceptability. However, the efficacy and safety of oral sulfate solution (OSS) preparations in patients with ulcerative colitis (UC) has not been well known. Therefore, we aimed to compare OSS and 2-L polyethylene glycol with ascorbic acid (PEG+Asc) for bowel preparation in inactive UC. Methods: A multicenter, randomized, single-blind study was conducted at six tertiary referral hospitals in Korea. Outpatients with UC who had stable disease activity were randomly allocated to the OSS group or the 2-L PEG+Asc group for bowel preparation before colonoscopy. The study outcomes included treatment efficacy, safety, tolerability, and acceptability. Bowel cleansing was assessed using the Boston Bowel Preparation Scale and rated as successful cleansing if the score was ≥6. Patient acceptance and tolerability were assessed using a 4-point ordinal scale. Additionally, disease activity and laboratory data before and after colonoscopy were evaluated to check for safety. Results: The OSS and 2-L PEG+Asc groups included 92 and 93 participants, respectively. No significant between-group difference was noted in successful cleansing (OSS [96.7%] vs 2-L PEG+Asc [97.8%], p=0.64). Moreover, the safety, acceptance, and tolerability were not significantly different (all p>0.05). Furthermore, no significant changes were found in serum electrolytes or disease activity in either group. Conclusions: OSS is effective for colonoscopy cleansing, has acceptable tolerability, and does not affect disease activity; thus, it can be used safely for bowel preparation in patients with inactive UC.

Interventional management is commonly used for traumatic injuries to the abdominal solid organs. The American Association for the Surgery of Trauma (AAST) and the World Society of Emergency Surgery (WSES) recently published guidelines for the management and treatment of liver, spleen, and kidney injuries, emphasizing the importance of interventions. Here, we discuss the characteristics of each organ and the procedure method for each organ that interventional radiologists need to know when treating trauma patients.

Abstract Planted forests are critical to climate change mitigation and constitute a major supplier of timber/non-timber products and other ecosystem services. Globally, approximately 36% of planted forest area is located in East Asia. However, reliable records of the geographic distribution and tree species composition of these planted forests remain very limited. Here, based on extensive in situ and remote sensing data, as well as an ensemble modeling approach, we present the first spatial database of planted forests for East Asia, which consists of maps of the geographic distribution of planted forests and associated dominant tree genera. Of the predicted planted forest areas in East Asia (948,863 km2), China contributed 87%, most of which is located in the lowland tropical/subtropical regions, and Sichuan Basin. With 95% accuracy and an F1 score of 0.77, our spatially-continuous maps of planted forests enable accurate quantification of the role of planted forests in climate change mitigation. Our findings inform effective decision-making in forest conservation, management, and global restoration projects.

Background/Aims Capsule endoscopy (CE) has shown that low-dose aspirin occasionally causes small bowel (SB) bleeding. We herein evaluated the protective effects of mucoprotective agents (MPAs) on SB bleeding in aspirin users using the nationwide database of claims data from the National Health Insurance Service (NHIS). Methods As CE is an insured procedure, we constructed an aspirin-SB cohort using NHIS claims data, with a maximum follow-up period of 24 months. Patients with anemia, melena, or hematochezia that occurred within 4 weeks before and after performing CE were suspected to have SB bleeding. A Cox proportional hazards regression model was used to determine the risk factors for SB bleeding. Subgroup analyses were conducted among patients who used acid suppressants, such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists. Results A total of 15,542 aspirin users were included. Anticoagulant use (hazard ratio [HR], 3.22), high Charlson comorbidity index score (≥ 2) (HR, 3.54), and PPI use (HR, 2.85) were significantly associated with SB bleeding, whereas eupatilin use (HR, 0.35) was a preventive factor. SB bleeding occurred more frequently in concurrent users of acid suppressants than in nonusers (1.3% vs. 0.5%). Subgroup analysis revealed that eupatilin significantly reduced the risk of SB bleeding in aspirin users with concurrent use of acid suppressants (HR, 0.23 vs. 2.55). Conclusions Eupatilin was associated with a reduced risk of SB bleeding in both aspirin users and those with concomitant use of acid suppressants. Eupatilin use should be considered for aspirin users, especially for those concomitantly taking acid suppressants.

AbstractThe photochemical process of photosynthesis is significantly influenced by the availability of nutrients. The purpose of this research is to ascertain how photosynthetic pigment function is affected by nutrient elemental changes caused by severe drought stress. Using elemental analysis, we looked at the changes in mineral nutrient composition in eastern white pine (Pinus strobus L) seedlings 32 days after drought treatment. According to our findings, severe drought resulted in a significant and non-significant decrease in the contents of Chl “b and a”, respectively. The elemental composition of iron (Fe), zinc (Zn), magnesium (Mg), potassium (K), phosphorus (P) and nitrogen (N) was measured. After severe drought treatment, leaf nutrient status showed a significant decline in total N (control-1.57 ± 0.1; drought-0.65 ± 0.07), P (control-959.4 ± 17; drought-645 ± 46), Mg (control-1030.4 ± 33; drought-750.7 ± 76), and K (control-3062.5 ± 32; drought-1853.3 ± 198), with a non-significant decrease in leaf Fe (control-120.3 ± 20; drought-98.9 ± 28) and increase in leaf Zn (control-33.49 ± 2; drought-39.05 ± 4). A positive correlation was found between the content of Fe, P, Mg, K, and N in leaf Chl “b”, but only a positive correlation was found between the content of Zn in leaf Chl “a” during severe drought. During severe drought, nutrient reallocation has a significant impact on leaf chlorophyll levels, as evidenced by this correlation.

Fine dust and bioaerosols are significant public health concerns, showing the importance of protective measures. In this study, natural-based trimethyl chitosan, permanently burdened with a positive charge, was successfully distributed on the surface of melt-blown polypropylene sheets through a metal rod coating process. This surface modification was confirmed through scanning electron microscopy and X-ray photoelectron spectroscopy, indicating the surface adsorption of trimethyl chitosan without chemical bonding. Modifying polypropylene mask filters yielded a positive surface zeta potential for 10–20 g/m2 coat weight, increasing the filtration efficiency to 55–94 % in a standard particle filtration test using paraffin oil as a liquid aerosol. The filtration efficiency remained higher than conventional non-treated mask filters even after the humidification of sheets. In addition, the filtration test against fine dust particles, such as titanium dioxide, was performed with trimethyl chitosan-modified mask filters that captured up to 100–800 µg/m3 titanium oxide particle concentrations, showing better filtration than conventional mask filters in high fine dust events. Trimethyl chitosan-modified mask filters also exhibited potent inhibition, bactericidal, and antiviral effects against HCoV-OC43, reducing the virus infection rate by 93.69 %. Thus, trimethyl chitosan could be applied to several existing filter membranes to protect against particulate matter and dangerous airborne pathogens.

Anthropogenic changes in water temperature can pose significant risk to thermoelectric and hydroelectric generation. In this study, we developed indicators of thermal risk (ITRs) to assess risk to water-dependent electricity generating assets under future climate. We projected future changes in water temperature and quantified ITRs for plants across the conterminous US for a baseline and future period. One goal of our study was to tailor ITRs to measure climate risks mediated by aquatic biota. When using local species’ thermal tolerances as thresholds, we estimated that future conditions would expose an additional 53 GW or 30 % of once-through-cooled thermoelectric power (OTE) capacity and an additional 7.1 GW (10 %) of total hydropower capacity to slightly higher risk. Meanwhile, the future proportion of species exposed to risk increased by 25 % (OTE) and 15 % (hydropower). Because seasonal timing can be important when understanding competing demands for cold water, we developed two metrics of risk timing (median date of exceeding thermal thresholds and the duration of exceedances). Although changes were small (

Objective To determine correlations of alternation motor rate (AMR), sequential motor rate (SMR), and maximum phonation time (MPT) with the severity of dysphagia in subacute stroke patients. Methods This was a retrospective chart review study. Data of 171 subacute stroke patients were analyzed. Patient’s AMR, SMR, and MPT data were collected from their language evaluations. Video fluoroscopic swallowing study (VFSS) was done. Data of dysphagia scales including penetration-aspiration scale (PAS), American Speech-Language-Hearing Association National Outcomes Measurement System (ASHA-NOMS) scale, clinical dysphagia scale (CDS), and videofluoroscopic dysphagia scale (VDS) were obtained. AMR, SMR, and MPT were compared between a non-aspirator group and an aspirator group. Correlations of AMR, SMR, and MPT with dysphagia scales were analyzed. Results AMR ("ka"), SMR, and modified Rankin Scale were significant associated factors between non-aspirator group and aspirator group, while AMR ("pa"), AMR ("ta"), and MPT were not. AMR, SMR, and MPT showed significant correlations with PAS score, ASHA-NOMS scale, CDS, VDS oral, and VDS pharyngeal scores. The cut-off value for distinguishing non-aspirator group and aspiration group was 18.5 for AMR ("ka") (sensitivity of 74.4%, specificity of 70.8%) and 7.5 for SMR (sensitivity of 89.9%, specificity of 61.0%). AMR and SMR were significantly lower in before-swallow aspiration group. Conclusion Articulatory diadochokinetic tasks that can be easily performed at the bedside would be particularly helpful in determining the oral feeding possibility of subacute stroke patients who cannot undergo VFSS, which is the gold standard for dysphagia assessment.

Objective To investigate the relationship between Trunk Impairment Scale (TIS) and lumbar spine bone mineral density (BMD) in subacute stroke patients. Methods Twenty-three subacute male stroke patients under the age of 65 were prospectively enrolled to exclude both postmenopausal and senile effects on BMD. The TIS, Berg Balance Scale, the Korean version of the Modified Barthel Index, and manual muscle test were measured at admission and 3 months after stroke onset. BMD of the bilateral lower extremities and lumbar vertebrae was measured by dual-energy X-ray absorptiometry 3 months after stroke onset. Results TIS at baseline (TIS_B) and TIS at 3 months after stroke (TIS_3m) showed significant correlations with lumbar BMD (TIS_B, r=0.522; TIS_3m, r=0.517). Through multiple regression analysis, the TIS_B was associated with lumbar BMD (adjusted R2=0.474). However, BMD of the bilateral lower extremities was not correlated with any clinical measurements except body mass index. Conclusion We found a relationship between TIS_B and lumbar BMD in subacute young male stroke patients. Stroke patients with poor trunk control in the early subacute stage would have low BMD of vertebral bones at 3 months. The TIS can be useful for estimating bone fragility in the lumbar vertebrae of subacute stroke patients.

Background/Aims Histamine-2 receptor antagonists (H2RA) are used to treat acid-related disorders and functional dyspepsia. In contrast to other H2RAs, nizatidine promotes gastric emptying (GE). We investigated the effects of nizatidine and famotidine on intragastric pH and the GE rate in rats exposed to stress. Materials and Methods We used 8-week-old male Wistar rats. Based on administration of water or drugs after an overnight fast, the animals were categorized into the nonstress-water, stress-water, stress-nizatidine, stress-famotidine, and stress-nizatidine with mosapride groups. The rats had access to pre-weighed food for 10 minutes, and those in the stress groups were exposed to 1 hour of restraint stress. Intragastric pH was measured under isoflurane anesthesia, and the GE rate was measured after the rats were sacrificed. Results The GE rate was significantly lower in the stress-water and stress-famotidine groups than in the nonstress-water group. However, GE in the stress-nizatidine and stress-nizatidine with mosapride group did not significantly differ from that in the nonstress- water group. The GE rate was significantly higher in the stress-nizatidine with mosapride than in the stress-famotidine group. Intragastric pH was significantly higher in the stress-nizatidine and stress-famotidine groups than in the stress-water group. Nonetheless, there was no significant difference in pH between the stress-nizatidine and stress-famotidine groups. The intragastric pH was slightly but significantly higher in the stress-nizatidine with mosapride group than in the stress-nizatidine and stress-famotidine groups. Conclusions In contrast to famotidine, nizatidine prevents stress-induced GE delay, which suggests that nizatidine is superior to other H2RAs for treatment of functional dyspepsia associated with delayed GE.

The lymphatic system provides a route for the spread of inflammation and malignancies. The identification of nodal stations and lymphatic pathways of tumor spread is important for tumor staging, choice of therapy, and the prediction of the prognosis of patients with malignant diseases. Because lymph node metastasis is common in primary intra-abdominal malignant tumors, its detection is essential for radiologists to understand the pattern of disease spread. Using schematic pictures and color-coded CT images, this pictorial essay describes the locations and nomenclature of the abdominal lymph nodes. Furthermore, the lymphatic drainage pathways of the upper and lower gastrointestinal tracts, liver, gallbladder, bile duct, and pancreas have been highlighted. In addition, lymph nodes belonging to the regional lymph nodes in malignant tumors arising from each organ are described, and certain cases are presented with images from patients.

ABSTRACTAlthough tibial nerve modulation has shown to induce positive changes in the overactive bladder (OAB), prolonged therapeutic effects using percutaneous stimulation have not yet been achieved. Intradetrusor onabotulinum toxin A injection can provide prolonged therapeutic effects; however, its delivery requires invasive measures. By applying local relief of tibial nerve neural entrapment with onabotulinum toxin A injection, this study investigated the feasibility and efficacy of combining the abovementioned two therapeutic strategies. An OAB animal model was developed using 12 adult Sprague–Dawley rats with cyclophosphamide intraperitoneal injection. A perineural injection site comparable to the tibial nerve perineural injection site and corresponding to that in humans was identified and developed in rats. The toxin was injected five days after establishing the OAB. The incision was made in the skin on the lateral surface of the thigh. The biceps femoris muscle was cut across, exposing the sciatic nerve and its three terminal branches: the sural, common peroneal, and tibial nerves, and 100 units of onabotulinum toxin A was injected into the surrounding tissue. Five days following injection, cystometry was performed. Inter-contraction time, contraction pressure, and interval of the disease state improved with statistical significance. The OAB animal model showed significant improvement with the tibial nerve perineural injection of botulinum toxin, thereby suggesting the possibility of a comparable treatment adaptation in humans.

Abstract Dissolved organic carbon (DOC) in throughfall plays a vital role in providing carbon and energy to organisms in forests. We utilized carbon isotope analysis to allocate the sources of throughfall DOC, including leaching from plant tissues, PM2.5 deposition on plant foliage, and precipitation. Rainwater, PM2.5, and throughfall samples were collected from pine and oak forests between March and November 2021. The mean concentration of throughfall DOC was 7.9 mg L−1, approximately six times higher than that of rainfall. The mean Δ14C of throughfall DOC was −38.2‰, ∼200‰ higher than that of rainwater or PM2.5. Mass balance estimates revealed that canopy leaching contributed to ∼83% of throughfall DOC, while desorption of PM2.5 and rainwater accounted for only ∼3% and ∼14% of throughfall DOC, respectively. These results clearly highlight canopy leaching as the primary source of carbon input to the forest floor, with a relatively minor contribution from PM2.5 desorption on leaves.

Abstract Background Due to sex‐specific differences in the incidence and clinical and histopathological characteristics of colorectal cancer (CRC), understanding the impact of sex on CRC may suggest sex‐targeted strategies for screening, treatment, and prevention, leading to improved prognosis of CRC. However, there have been few studies investigating the sex‐specific differences in CRC in the Republic of Korea. We aimed to assess sex differences in CRC in the Republic of Korea. Methods This was a retrospective, multicenter, cohort study of patients diagnosed with CRC between January 2012 and December 2013 at nine hospitals. Patients who had an uncertain CRC stage, were diagnosed with other cancers within 5 years, had carcinoma in situ, non‐epithelial cancer, or primary cancer other than CRC, were excluded. Factors associated with overall survival or progression‐free survival were investigated using Cox regression analysis. Cumulative probability of metachronous lesions was compared using the Kaplan–Meier estimator survival analysis and we compared the survival curves of each group using a log‐rank test. Outcomes were compared using the chi‐square, Fisher's exact, or Student's t‐test, as appropriate. Results Three thousand one hundred and forteen patients (1999 men, 1315 women) were included. There was no significant difference in the age at onset between men and women. The proportion of patients diagnosed through regular health check‐ups, and asymptomatic at time of diagnosis, was higher in men (48.9% men vs. 42.0% women, p

We present a novel background-independent framework for cosmic inflation, starting with a matrix model. In this framework, inflation is portrayed as a dynamic process responsible for the generation of both space and time. This stands in contrast to conventional inflation, which is characterized as a mere (exponential) expansion of an already existing spacetime, driven by the vacuum energy associated with an inflaton field. We observe that the cosmic inflation is triggered by the condensate of Planck energy into a vacuum and responsible for the dynamical emergence of spacetime. The emergent spacetime picture admits a background-independent formulation so that the inflation is described by a conformal Hamiltonian system which requires neither an inflaton field nor an ad hoc inflation potential. This implies that the emergent spacetime may incapacitate all the rationales to introduce the multiverse hypothesis.

Background/Aims: Golimumab has been used for patients with ulcerative colitis (UC) since 2013. However, there is limited data on the effectiveness and safety of the real-world use of golimumab in Asian patients. Methods: This was a multicenter, prospective, observational study. We enrolled patients with moderate-to-severe UC who were administered subcutaneous golimumab at 46 medical centers between May 2014 and November 2019. The primary outcome was the effectiveness and safety of golimumab at week 22. Clinical outcomes and adverse events were assessed according to partial Mayo score at weeks 0, 2, 6, 14, and 22. Results: A total of 130 patients were included (mean age: 45.7±16.0 years). The clinical response/ remission rates at weeks 2, 6, 14, and 22 were 40.4%/22.9%, 56.0%/35.8%, 70.6%/49.5%, and 67.9%/48.6%, respectively. Based on full Mayo score at week 14, clinical response and remission rates were 84.2% and 39.5%, respectively. Mucosal healing rate was 65.8%. In multivariate analysis with logistic regression, longer disease duration was significantly associated with a higher clinical response rate (adjusted odds ratio [aOR], 1.136; 95% confidence interval [CI], 1.006 to 1.282; p=0.040 at week 6; aOR, 1.256; 95% CI, 1.049 to 1.503; p=0.013 at week 22). A higher baseline Mayo endoscopic subscore was significantly associated with a lower clinical response rate at week 6 (aOR, 0.248; 95% CI, 0.089 to 0.692; p=0.008). The incidence of adverse drug reactions was 4.6% (6/130, nine events). No serious unexpected adverse drug reactions or deaths were reported. Conclusions: Golimumab was effective and safe as an induction and maintenance treatment for Korean patients with moderate-to-severe UC.

Abstract Background Autophagy is elevated in metastatic tumors and is often associated with active epithelial‐to‐mesenchymal transition (EMT). However, the extent to which EMT is dependent on autophagy is largely unknown. This study aimed to identify the mechanisms by which autophagy facilitates EMT. Methods We employed a liquid chromatography‐based metabolomic approach with kirsten rat sarcoma viral oncogene (KRAS) and liver kinase B1 (LKB1) gene co‐mutated (KL) cells that represent an autophagy/EMT‐coactivated invasive lung cancer subtype for the identification of metabolites linked to autophagy‐driven EMT activation. Molecular mechanisms of autophagy‐driven EMT activation were further investigated by quantitative real‐time polymerase chain reaction (qRT‐PCR), Western blotting analysis, immunoprecipitation, immunofluorescence staining, and metabolite assays. The effects of chemical and genetic perturbations on autophagic flux were assessed by two orthogonal approaches: microtubule‐associated protein 1A/1B‐light chain 3 (LC3) turnover analysis by Western blotting and monomeric red fluorescent protein‐green fluorescent protein (mRFP‐GFP)‐LC3 tandem fluorescent protein quenching assay. Transcription factor EB (TFEB) activity was measured by coordinated lysosomal expression and regulation (CLEAR) motif‐driven luciferase reporter assay. Experimental metastasis (tail vein injection) mouse models were used to evaluate the impact of calcium/calmodulin‐dependent protein kinase kinase 2 (CAMKK2) or ATP citrate lyase (ACLY) inhibitors on lung metastasis using IVIS luciferase imaging system. Results We found that autophagy in KL cancer cells increased acetyl‐coenzyme A (acetyl‐CoA), which facilitated the acetylation and stabilization of the EMT‐inducing transcription factor Snail. The autophagy/acetyl‐CoA/acetyl‐Snail axis was further validated in tumor tissues and in autophagy‐activated pancreatic cancer cells. TFEB acetylation in KL cancer cells sustained pro‐metastatic autophagy in a mammalian target of rapamycin complex 1 (mTORC1)‐independent manner. Pharmacological inhibition of this axis via CAMKK2 inhibitors or ACLY inhibitors consistently reduced the metastatic capacity of KL cancer cells in vivo. Conclusions This study demonstrates that autophagy‐derived acetyl‐CoA promotes Snail acetylation and thereby facilitates invasion and metastasis of KRAS‐LKB1 co‐mutated lung cancer cells and that inhibition of the autophagy/acetyl‐CoA/acetyl‐Snail axis using CAMKK2 or ACLY inhibitors could be a potential therapeutic strategy to suppress metastasis of KL lung cancer.

Abstract We aimed to evaluate the radiographic and clinical outcomes after gamma knife radiosurgery (GKRS) for trigeminal schwannomas (TSs). A total of 87 patients who underwent GKRS for TSs between 1990 and 2020 were enrolled. The mean tumor volume was 4.3 cm3. The median prescribed dose for the margins of the tumor was 13 Gy. The median follow-up duration was 64.3 months (range 12.0–311.5 months). The overall local tumor control rate was 90%, and the symptom response rate was 93%. The response rate for each symptom was 88% for facial pain, 97% for facial sensory change, and 86% for cranial nerve deficits. Nineteen (22%) patients showed transient swelling, which had regressed at the time of the last follow-up. Cystic tumors were associated with transient swelling (p = 0.04). A tumor volume of

Determining the overall US prevalence of Inflammatory Bowel Disease (IBD) is essential to national level prevention programs and population risk assessment; however currently US IBD prevalence remains uncertain. We used US National Health and Nutrition Examination Survey (NHANES) data to estimate the population-based prevalence of a self-reported history of medically diagnosed IBD, comparing to prior reports. Lifetime IBD prevalence for adults aged 20 + years was estimated in the independently conducted NHANES II (1976–80) and NHANES 2009–10 surveys. Participants were considered to have IBD if they reported being told by a physician they had Crohn’s Disease (CD) or ulcerative colitis (UC). Clinically relevant NHANES data were analyzed to assess the self-reports. Survey design variables and sample weights were used to account for the complex survey design. The NHANES 2009–10 US IBD diagnosed prevalence was 1.2% (95% CI 0.8,1.6%), or an estimated 2.3 million persons. UC prevalence was 1.0% (95% CI 0.5,1.4%; 1.9 million persons) and CD prevalence was 0.3% (95% CI 0.1,0.4%; 578,000 persons). NHANES II UC prevalence was 1.0 (95% CI 0.8,1.2%), similar to 2009–10. UC prevalence was higher for ages ≥ 50 years in both surveys. NHANES 2009–10 data showed no UC sex differences, but women had higher UC prevalence in NHANES II. Remarkably, UC prevalence was similar between the two NHANES surveys fielded 30 years apart. The NHANES data are consistent with IBD prevalences reported in previous US nationally representative surveys, indicating that diagnosed IBD may affect approximately 1% of the US adult population.

Purpose This clinical study sought to evaluate the possible clinical effectiveness and practicality of URINO, an innovative, incisionless, and disposable intravaginal device, designed for patients suffering from stress urinary incontinence. Methods A prospective, multicenter, single-arm clinical trial was carried out, involving women diagnosed with stress urinary incontinence who used a self-inserted, disposable intravaginal pessary device. Comparisons were made between the results of the 20-minute pad-weight gain (PWG) test at baseline and visit 3, where the device was applied. After 1 week of device usage, compliance, satisfaction, the sensation of a foreign body, and adverse events were assessed. Results Out of 45 participants, 39 completed the trial and expressed satisfaction within the modified intention-to-treat group. The average 20-minute PWG of participants was 17.2±33.6 g at baseline and significantly dropped to 5.3±16.2 g at visit 3 with device application. A total of 87.2% of participants exhibited a reduction ratio of PWG by 50% or more, surpassing the clinical trial success benchmark of 76%. The mean compliance was recorded as 76.6%±26.6%, the average visual analogue scale score for patient satisfaction was 6.4±2.6, and the sensation of a foreign body, measured on a 5-point Likert scale, was 3.1±1.2 after 1 week of device use. No serious adverse events were reported; there was 1 instance of microscopic hematuria and 2 cases of pyuria, all of which recovered. Conclusions The investigated device demonstrated significant clinical effectiveness and safety for patients with stress urinary incontinence. It was easy to use, showing favorable patient compliance. We propose that these disposable intravaginal pessaries could potentially be an alternative treatment for patients with stress urinary incontinence who are seeking nonsurgical options or are unable to undergo surgery. Trial Registration The study was registered as a clinical trial (KCT0008369).