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Purpose: This study aimed to investigate the clinical significance of E-cadherin expression levels in colorectal cancer tissues and explore the relationship between E-cadherin expression and tumor node metastasis (TNM) stage. The goal was to establish a more accurate prognostic prediction for colorectal cancer patients by analyzing E-cadherin expression levels alongside TNM staging., Methods: The study examined colorectal cancer patients by dividing them into groups based on E-cadherin expression levels. It then assessed their 5-year event-free survival (EFS) and disease-specific survival (DSS) hazard ratios (HRs). Additionally, the prognosis of patients was analyzed by combining E-cadherin expression levels with TNM staging, particularly focusing on patients in stages III and IV., Results: The E-cadherin Low group had significantly worse outcomes, with HRs of 2.30 for EFS and 2.76 for DSS compared to the E-cadherin High group. When combined with TNM stage III/IV, patients with E-cadherin Low expression showed a poor prognosis, with HRs of 1.93 for EFS and 2.35 for DSS compared to those with E-cadherin High expression at the same TNM stage., Conclusions: Low levels of E-cadherin expression are associated with a poor prognosis and decreased survival in colorectal cancer patients. Combining E-cadherin expression levels with TNM staging provides a more precise prediction of patient prognosis and survival, potentially guiding personalized treatment strategies., Competing Interests: Declarations. Ethical approval: All methods were carried out in accordance with relevant guidelines and regulations. Ethical approval for study was obtained from Institutional Review Board of Gachon University Gil Medical Center (GBIRB2023-224). Informed consent was obtained from all the participants. Consent for publication: All participants involved in the study have provided written informed consent for the publication of anonymized data and findings derived from the research. The authors affirm that no identifiable personal information or sensitive data has been included in this publication. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: As the roles of chemotherapy (Chemo) and radiation therapy (Radio) in the definitive treatment of breast cancer have expanded, a broader understanding of the factors associated with breast cancer-related lymphedema (BCRL) has become increasingly essential. Therefore, we investigated the association between multimodality treatment and the risk of BCRL., Methods: In this retrospective study conducted using National Health Insurance data and the Korea National Cancer Incidence Database (2006-2017), 114,638 participants who underwent Surgery (Surg) or Chemo within 6 months after breast cancer diagnosis were enrolled, and the effect of multimodality treatment on the risk of BCRL was analyzed using the Cox proportional-hazards model. Multimodality treatment administered through six months of treatment was grouped as only Surg; Surg/Chemo; Surg/ Chemo/Radio; Surg/Radio; only Chemo; and Chemo/Radio., Results: The risk of BCRL was higher in the Surg/Chemo group (hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.43-1.65), Surg/Chemo/Radio group (HR: 1.51, 95% CI: 1.43-1.65), only Chemo group (HR: 1.58, 95% CI: 1.45-1.71), and Chemo/Radio group (HR: 1.13, 95% CI: 1.00-1.29) in comparison with the only Surg group., Conclusion: BCRL occurrence is an after-effect of complex breast cancer treatments, and the risk may vary depending on the treatment method, including Surg, chemo, and radio. Our findings suggest that multidisciplinary strategies are required to minimize the risk of BCRL development in patients with breast cancer., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures contributing to this work complied with the ethical standards of the relevant national and institutional committees on human experimentation and the Helsinki Declaration of 1975, as revised in 2008. As the NHIS data did not contain any identifying information, the study was approved by the Institutional Review Board of Seoul National University Hospital (E-2206–076-1332). Because we used de-identified data, the need for informed consent was waived by the Institutional Review Board of Seoul National University Hospital (E-2206–076-1332). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objectives: The data were collected to obtain the complete genome sequence of Pseudarthrobacter sp. NIBRBAC000502770, isolated from the rhizosphere of Sasamorpha in a heavy metal-contaminated coal mine in Hongcheon, Republic of Korea. The objective was to explore the strain's genetic potential for plant growth promotion and heavy metal resistance, particularly arsenate and copper. The aim focused on identifying microbes that enhance plant growth in metal-tolerant environments and evaluating the strain's bioremediation and agricultural uses. This study sought key genes for bioremediation and agricultural applications in contaminated soils, aiding sustainable management and biotechnology., Data Description: We report the complete genome sequence of Pseudarthrobacter sp. NIBRBAC000502770, isolated from a coal mine in Hongcheon, Republic of Korea. The genome contains a chromosome (4,403,796 bp) and a plasmid (74,326 bp, named pMK-1) with 286-fold coverage. Genome annotation identified 4,209 genes, including 3,926 protein-coding genes, 51 tRNA genes, and 15 rRNA genes, with a G + C content of 66.1%. Functional analysis revealed genes related to plant growth promotion and heavy metal resistance, such as arsenate (arsR, arsC) and copper (copC, copD) resistance genes. Genes involved in auxin biosynthesis suggest potential agricultural applications. The genome and plasmid are available in GenBank (CP041198.1, CP014497.1), offering insights into bioremediation and plant growth in metal-contaminated environments., Competing Interests: Declarations. Ethics approval and consent to participate: The bacterial strain was obtained from a National Institute of Biological Resources (NIBR) with permission. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Brain-computer interface (BCI) technology can enhance neural plasticity and motor recovery in persons with stroke. However, the effects of BCI training with motor imagery (MI)-contingent feedback versus MI-independent feedback remain unclear. This study aimed to investigate whether the contingent connection between MI-induced brain activity and feedback influences functional and neural plasticity outcomes. We hypothesized that BCI training, with MI-contingent feedback, would result in greater improvements in upper limb function and neural plasticity compared to BCI training, with MI-independent feedback., Methods: This randomized controlled trial included persons with chronic stroke who underwent BCI training involving functional electrical stimulation feedback on the affected wrist extensor. Primary outcomes included the Medical Research Council (MRC) scale score for muscle strength in the wrist extensor (MRC-WE) and active range of motion in wrist extension (AROM-WE). Resting-state electroencephalogram recordings were used to assess neural plasticity., Results: Compared to the MI-independent feedback BCI group, the MI-contingent feedback BCI group showed significantly greater improvements in MRC-WE scores (mean difference = 0.52, 95% CI = 0.03-1.00, p = 0.036) and demonstrated increased AROM-WE at 4 weeks post-intervention (p = 0.019). Enhanced functional connectivity in the affected hemisphere was observed in the MI-contingent feedback BCI group, correlating with MRC-WE and Fugl-Meyer assessment-distal scores. Improvements were also observed in the unaffected hemisphere's functional connectivity., Conclusions: BCI training with MI-contingent feedback is more effective than MI-independent feedback in improving AROM-WE, MRC, and neural plasticity in individuals with chronic stroke. BCI technology could be a valuable addition to conventional rehabilitation for stroke survivors, enhancing recovery outcomes., Trial Registration: CRIS (KCT0009013)., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board of the Rehabilitation Hospital (NRC-2020-01-007) and registered at CRIS (KCT0009013). Participants provided informed consent before enrolment in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Paclitaxel resistance and recurrence are major obstacles in ovarian cancer, which is the leading cause of death among gynecologic cancers. During cancer cell progression, cyclin-dependent kinase 1 (CDK1) drives cells through the G2 phase and into mitosis. In this study, we demonstrated that CDK1 played a crucial role in switching paclitaxel-resistant ovarian cancer cells from mitotic arrest to apoptosis following combined treatment with paclitaxel and duloxetine, an antidepressant known as a serotonin-norepinephrine reuptake inhibitor (SNRI)., Methods: Cell viability was assessed by MTT assay. Apoptotic cell death and mitochondrial membrane potential (MMP) were detected by flow cytometry. Protein expression levels were explored using western blotting. Mitochondrial and cytosolic fractionation were performed to determine the mitochondrial localization of proteins. Immunofluorescence was used to detect protein expression levels and localization., Results: Combined treatment with paclitaxel and duloxetine induced apoptotic cell death in paclitaxel-resistant ovarian cancer cells. We suggested that combined treatment of these drugs induced CDK1 activation and increased mitochondrial localization of activated CDK1, which caused phosphorylation of the antiapoptotic Bcl-2 and Bcl-xL proteins. Selective CDK1 inhibitors blocked Bcl-2 and Bcl-xL phosphorylation induced by paclitaxel and duloxetine, and strongly suppressed apoptotic cell death. Furthermore, we demonstrated that S6K is a potential upstream mediator of the proapoptotic activation of CDK1., Conclusion: Taken together, switching CDK1 to a proapoptotic role through the combination of paclitaxel and duloxetine could overcome paclitaxel resistance in ovarian cancer cells, providing promising therapeutic strategies for treating paclitaxel-resistant ovarian cancer., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The posterior maxilla and skull base is a region with a complex anatomy. Accurate resection of the pterygoid plate is critical during a maxillectomy procedure. However, there is a paucity of functional and anatomical studies on the pterygoid plate and skull base. This study aimed to investigate functional anatomy of the pterygoid plate and its surrounding structures in the posterior maxilla to provide a better understanding of surgical procedures in this region., Methods: 3D software was used to measure 3D distances, angles, and areas of key anatomical landmarks on CT images of 100 hemifaces. Morphological classification of pterygoid plates was then performed., Results: Results of comparing right and left pterygoid plates revealed no significant differences in dimensions or angles. Comparisons between sexes revealed that a few parameters were significantly different (P < 0.01), including pterygoid height on the left side, distance from the zygomatico-maxillary buttress to the infraorbital fissure (Zy-IOF), and area of the left lateral pterygoid plate. The morphology of the lateral pterygoid plate was classified into four types based on the shape of the middle region: middle convex (42%), double concave (36%), flattened (10%), and middle concave (12%). The morphology of pterygoid plates was classified based on the divergence of medial and lateral pterygoid plates, with the narrow type (56%) being more common than the wide type in this study cohort., Conclusions: This 3D digital anatomical study measured key landmarks for maxillary resection. Such measurement has never been reported. This anatomical study provides surgeons with information on the anatomy of the posterior maxilla and allows for safer and more accurate resection of the difficult-to-resect posterior maxilla., Competing Interests: Declarations. Ethics approval and consent to participate: This retrospective study was exempted from approval by the Institutional Review Board (IRB) of Seoul National University Dental Hospital (SNUDH) (IRB number: ERI22002). The requirement for informed consent was waived due to the retrospective nature of the study. All methods were performed in accordance with the relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: We aimed to assess the incidence of infective endocarditis (IE) and evaluate the impact of hypertension (HTN) with underweight on the risk of IE among patients with diabetic mellitus (DM) using a nationwide population-based cohort in Korea., Methods: We identified 2,603,012 participants (57.4 ± 12.3 years) in the national health insurance database. Of these, 374,586 were normotensive, 750,006 were at pre-HTN status, and the remainder had HTN. The risk of IE was compared between the groups, and the impact of being underweight (body mass index < 18.5) was also evaluated., Results: During follow-up (7.14 years; interquartile range 6.01-8.08 years), 1,703 cases of IE occurred; 168 (0.0647 person per 1000 person-years [PY]), 303 (0.05836 per 1000 PY), and 1,232 (0.12235 per 1000 PY) in normotensive, pre-HTN and HTN group, respectively. Hypertensive participants presented a higher risk of IE (subdistribution hazard ratio, 1.360; 95% confidence interval, 1.152-1.607) than normotensive participants. Being underweight increased the risk of IE by 90% among subjects with HTN. In subgroup analysis, age, duration of DM, insulin use, and habitual factors were not associated with the incidence of IE., Conclusions: Diabetic patients may require rigorous blood pressure control and simultaneous avoidance of excessive weight loss to prevent IE., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the institutional review board of Soongsil University (Approval no. SSU-202003-HR-201-01). The requirement for written informed consent was waived in the present study because data in the K-NHIS database are anonymized in adherence to strict confidentiality guidelines. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Lymph node (LN) metastasis is an important prognostic factor in the ampulla of Vater (AoV) adenocarcinoma. Various LN parameters have been proposed, but their prognostic efficacy has not been compared in the same population. We aimed to evaluate the prognostic values of LN parameters in AoV adenocarcinoma patients who underwent surgical resection and adjuvant treatment based on the long-term follow-up data., Methods: A total of 86 patients with surgically resected AoV adenocarcinoma followed by adjuvant treatment were analyzed. We evaluated the prognostic values of various LN parameters such as pathologic N stage, number of metastatic regional LN (LNN), LN ratio (LNR), and log odds of positive LNs (LODDS). Each LN parameter was separately analyzed using Cox regression models with the same confounders., Results: The median follow-up period was 69.4 months, and the median overall survival (OS) was 114 months. The median number of dissected LNs is 15, with an interquartile range of 8 to 25. In the univariable analyses, all LN parameters showed significant prognostic efficacy for OS, disease-free survival (DFS), and distant metastasis-free survival (DMFS). In the multivariable Cox regression analyses, LNN ≥ 2 was a statistically significant prognostic factor for OS (hazard ratio (HR) 2.10, 95% confidence interval (CI), 1.11-3.97; p = 0.022), DFS (HR 2.51, 95% CI 1.28-4.93; p = 0.007), and DMFS (HR 2.74, 95% CI 1.39-5.41; p = 0.004). LNR showed significant prognostic performance for DFS (HR 2.35, 95% CI 1.23-4.50; p = 0.010), and DMFS (HR 2.26, 95% CI 1.17-4.35; p = 0.015). N stage showed significant prognostic performance in DFS (HR 1.55 for pN1; p = 0.243 and HR 4.31 for pN2; p = 0.003), DMFS (HR 1.46 for pN1; p = 0.323 and 4.59 for pN2; p = 0.002). LODDS and the presence of LN metastasis, did not demonstrate significant prognostic value across survival outcomes., Conclusions: LN parameters showed good long-term predictive performance in AoV adenocarcinoma patients treated with curative resection and adjuvant treatments. Among LN parameters, LNN ≥ 2 showed better prognostic value than others. Further large-scale studies are needed to validate the clinical usefulness of various LN parameters., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the institutional review board of Seoul National University Hospital, and written informed consent was waived due to its retrospective nature. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Accurate measurement of the hip-knee-ankle (HKA) angle is essential for informed clinical decision-making in the management of knee osteoarthritis (OA). Knee OA is commonly associated with varus deformity, where the alignment of the knee shifts medially, leading to increased stress and deterioration of the medial compartment. The HKA angle, which quantifies this alignment, is a critical indicator of the severity of varus deformity and helps guide treatment strategies, including corrective surgeries. Current manual methods are labor-intensive, time-consuming, and prone to inter-observer variability. Developing an automated model for HKA angle measurement is challenging due to the elaborate process of generating handcrafted anatomical landmarks, which is more labor-intensive than the actual measurement. This study aims to develop a ResNet-based deep learning model that predicts the HKA angle without requiring explicit anatomical landmark annotations and to assess its accuracy and efficiency compared to conventional manual methods., Methods: We developed a deep learning model based on the variants of the ResNet architecture to process lower limb radiographs and predict HKA angles without explicit landmark annotations. The classification performance for the four stages of varus deformity (stage I: 0°-10°, stage II: 10°-20°, stage III: > 20°, others: genu valgum or normal alignment) was also evaluated. The model was trained and validated using a retrospective cohort of 300 knee OA patients (Kellgren-Lawrence grade 3 or higher), with horizontal flip augmentation applied to double the dataset to 600 samples, followed by fivefold cross-validation. An extended temporal validation was conducted on a separate cohort of 50 knee OA patients. The model's accuracy was assessed by calculating the mean absolute error between predicted and actual HKA angles. Additionally, the classification of varus deformity stages was conducted to evaluate the model's ability to provide clinically relevant categorizations. Time efficiency was compared between the automated model and manual measurements performed by an experienced orthopedic surgeon., Results: The ResNet-50 model achieved a bias of - 0.025° with a standard deviation of 1.422° in the retrospective cohort and a bias of - 0.008° with a standard deviation of 1.677° in the temporal validation cohort. Using the ResNet-152 model, it accurately classified the four stages of varus deformity with weighted F1-score of 0.878 and 0.859 in the retrospective and temporal validation cohorts, respectively. The automated model was 126.7 times faster than manual measurements, reducing the total time from 49.8 min to 23.6 sec for the temporal validation cohort., Conclusions: The proposed ResNet-based model provides an efficient and accurate method for measuring HKA angles and classifying varus deformity stages without the need for extensive landmark annotations. Its high accuracy and significant improvement in time efficiency make it a valuable tool for clinical practice, potentially enhancing decision-making and workflow efficiency in the management of knee OA., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was obtained from the Institutional Research and Ethics Board of Seoul Medical Center (SEOUL 2023-12-002-001), Republic of Korea. The study was conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki. No patient-identifiable information was included in the manuscript, and all data were anonymized to ensure confidentiality. As this was a retrospective study, informed consent was waived. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: The adoption of tethered mobile personal health records provides not only medical information to patients but also various convenience functions related to hospital use, thereby increasing accessibility to healthcare services and promoting patient engagement. We analyse the tethered mobile personal health records app's usage logs to determine how it can contribute to improving medical service accessibility and patient engagement., Methods: Log data, that comprised menu type, log time, and date, were collected from the mobile personal health records app of a tertiary referral hospital. Clinical information, including patients' demographics and visit type, was collected from the clinical research warehouse system. The usage log was analysed in terms of the type of visit, service function, and time period., Results: Outpatients accounted for 34% of the total app usage and was the most app-accessed visit type. The most utilized menu functions were lab test and visit schedule for visits or non-visits. For Inpatient and Health check-ups, menu usage patterns showed a focus on lab test results. While investigations and other menu usage showed double peaks in the morning and afternoon, peak usage of lab test results correlated with inpatient blood sampling times, which was around 9 am., Discussion: App menus to access health information, particularly blood tests, emerged as the most accessed menu. Hence, when compared with blood sampling times and hospital information system usage patterns, encounters occurring in the hospital majorly impacted patient app use. For improved patient engagement, improving lab test function should be the priority., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Institutional Review Board (IRB) of the Asan Medical Center, South Korea (approval No. 2022 − 0603). MCMH is a service designed to assist in medical treatment. The notice and consent for the use of personal information are disclosed in the terms and conditions of the application. The data analyzed in this study were collected retrospectively and processed under pseudonymization. Consequently, explicit consent from the participants was not obtained. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study aimed to compare clinical and radiographic outcomes for a new tibial component (Attune S +) and the previous design (Attune S) in total knee arthroplasty (TKA) patients using ATTUNE® posterior stabilized (PS) prosthesis and also assessed related factors for the development of tibial radiolucent line(RLL)., Methods: This retrospective study included 362 knees (179 Attune S, 183 Attune S +) with an average 4 years (range, 2-8) follow-up. Clinical outcomes, radiologic parameters and the incidence of RLL around the tibial component were compared through the serial assessment. For the subgroup analysis, radiologic parameters were compared between patients with and without RLL., Results: There was no significant difference in terms of clinical outcomes and radiologic parameters between two designs. The incidence of RLL was not different through the serial follow-up (P > 0.05). In the subgroup analysis, the preoperative medial proximal tibial angle (83.7° versus 85.0°, P = 0.01) was smaller and preoperative hip-knee-ankle angle (169.1° versus 171.8°, P = 0.01) has more varus in the group with RLL than those without., Conclusions: The clinical and radiologic outcomes including the incidence of tibial RLL between new design and predecessor were not significantly different at average 4 years follow-up. The development of tibial RLL was associated with preoperative varus deformity of tibia and lower limb alignment., Competing Interests: Declarations Ethics approval and consent to participate This study had been approved from IRB (KHNMC 2023–10-012). Consent for publication Agreed. Competing interests None., (© 2024. The Author(s).)

Background: Microalgae have emerged as sustainable alternatives to fossil fuels and high-value petrochemicals. Despite the commercial potential of microalgae, their low biomass productivity is a significant limiting factor for large-scale production. In the photoautotrophic cultivation of microalgae, achievable cell density levels depend on the light transmittance of the production system, which can significantly decrease the photosynthetic rate and biomass production. In contrast, the mixotrophic cultivation of microalgae using heterotrophic carbon sources enables high-density cultivation, which significantly enhances biomass productivity. The identification of optimal production conditions is crucial for improving biomass productivity; however, it is typically time- and resource-consuming. To overcome this problem, high-throughput screening (HTS) system presents a practical approach to maximize biomass and lipid production and enhance the industrial applicability of microalgae., Results: In this study, we proposed a two-step HTS assay that allows effective screening of heterotrophic conditions compatible with new microalgal isolates. To confirm the effectiveness of the HTS assay, three microalgal isolates with distinctive morphological and genetic traits were selected. Suitable cultivation conditions, including various heterotrophic carbon sources, substrate concentrations, and temperatures, were investigated using a two-step HTS assay. The optimized conditions were validated at the flask scale, which confirmed a significant enhancement in the biomass and lipid productivity of each isolate. Moreover, the two-step HTS assay notably enhanced economic and temporal efficiency compared to conventional flask-based optimization., Conclusions: These results suggest that our two-step HTS assay is an efficient strategy for investigating and optimizing microalgal culture conditions to maximize biomass and lipid productivity. This approach has the potential to enhance the industrial applicability of microalgae and facilitate the seamless transition from laboratory to field applications., (© 2024. The Author(s).)

Objectives: Cutibacterium acnes is a Gram-positive bacterium commonly found on human skin, particularly in sebaceous areas. While it is typically considered a commensal, specific strain types based on single locus sequence typing (SLST) have been associated with pathogenic conditions or healthy skin. Recently, SLST D1 strains, part of phylotype IA1, have received attention for their potential benefits related to skin health. However, their genetic characteristics remain underexplored. Therefore, the whole genome of C. acnes CN6, an SLST D1 strain isolated from the facial skin of a healthy individual, was sequenced to expand the understanding of SLST D1 strains and identify genomic features that may support skin health., Data Description: The whole genome sequencing of C. acnes CN6 was conducted using MinION reads based on de novo assembly, revealing a single circular complete chromosome. With the length of 2,550,458 bp and G + C content of 60.04%, the genome contains 2,492 genes, including 2,433 CDSs, 9 rRNAs, 46 tRNAs, 4 ncRNAs, and 134 pseudo genes. Previously predicted virulence proteins of C. ances were detected in the genome. Genome comparation with 200 C. acnes strains isolated from healthy facial skin revealed SLST D1 strain-specific genes and a unique variant of the znuC gene in D1 strains., (© 2024. The Author(s).)

Recently, methane has been considered a next-generation carbon feedstock due to its abundance and it is main component of shale gas and biogas. Methylomonas sp. DH-1 has been evaluated as a promising industrial bio-catalyst candidate. Succinate is considered one of the top building block chemicals in the agricultural, food, and pharmaceutical industries. In this study, succinate production by Methylomonas sp. DH-1 was improved by combining adaptive laboratory evolution (ALE) technology with genetic engineering in the chromosome of Methylomonas sp. DH-1, such as deletion of bypass pathway genes (succinate dehydrogenase and succinate semialdehyde dehydrogenase) or overexpression of genes related with succinate production (citrate synthase, pyruvate carboxylase and phosphoenolpyruvate carboxylase). Through ALE, the maximum consumption rate of substrate gases (methane and oxygen) and the duration maintaining high substrate gas consumption rates was enhanced compared to those of the parental strain. Based on the improved methane consumption, cell growth (OD 600 ) increased more than twice, and the succinate titer increased by ~ 48% from 218 to 323 mg/L. To prevent unwanted succinate consumption, the succinate semialdehyde dehydrogenase gene was deleted from the genome. The first enzyme of TCA cycle (citrate synthase) was overexpressed. Pyruvate carboxylase and phosphoenolpyruvate carboxylase, which produce oxaloacetate, a substrate for citrate synthase, were also overproduced by a newly identified strong promoter. The new strong promoter was screened from RNA sequencing data. When these modifications were combined in one strain, the maximum titer (702 mg/L) was successfully improved by more than three times. This study demonstrates that successful enhancement of succinic acid production can be achieved in methanotrophs through additional genetic engineering following adaptive laboratory evolution., (© 2024. The Author(s).)

Background: Pressure sores significantly affect elderly patients, with the sacrum being especially vulnerable, often due to its proximity to the anus and potential for fecal contamination. Despite preventive measures such as frequent repositioning and specialized cushions, some sores still necessitate surgical intervention. Postoperative care focuses on monitoring, hygiene, and pressure alleviation. This study assessed the efficacy of Closed-Incision Negative Pressure Wound Therapy (CI-NPWT) for postoperative wound management in patients with sacral pressure sores treated with local flaps., Methods: A retrospective analysis was performed on sacral sore patients who underwent reconstructive surgery from March 2019 through April 2023. Surgical procedures involved debridement and wound coverage using gluteal artery perforator-based fasciocutaneous flaps, followed by postoperative monitoring. Patients were grouped into conventional monitoring or NPWT management, with the latter utilizing the INFOV.A.C. The therapy unit was calibrated to 125 mmHg. Data on patient demographics, flap metrics, fluid drainage amounts, and six-month postoperative outcomes were collected, and then analyzed with SPSS Statistics., Results: In this study of 52 patients with sacral pressure sores, the NPWT group (n = 25) showed significantly fewer flap complications and a lower drainage volume on the seventh postoperative day (mean 17.2 cc) compared to the conventional dressing group (mean 27.8 cc, P < 0.05). No postoperative complications were observed in the NPWT group, whereas the conventional group (n = 27) experienced one infection and three cases of dehiscence. Both groups achieved a 100% flap survival rate., Conclusion: Closed-incision negative pressure wound therapy (CI-NPWT) shows promise in reducing wound dehiscence and infection rates in elderly patients undergoing sacral pressure sore reconstruction with local flaps. However, further research with larger, randomized studies is needed to confirm its effectiveness as an alternative to conventional postoperative care., Trial Registration: The study was retrospectively registered by the Institutional Review Board of Seoul Metropolitan Government-Seoul National University Boramae Medical Center (No. 20-2023-25, Date: Mar. 24 2023)., (© 2024. The Author(s).)

Background: Microalgae are potential sustainable resources for the production of value-added chemicals that can be used as biofuels, pharmaceuticals, and nutritional supplements. Arachidonic acid (ARA), a omega-6 fatty acid, plays a crucial role in infant development and immune response, and can be used in cosmetics and pharmaceuticals. Demand for industrial-scale ARA production is continuously increasing because of its broad applicability. To address this demand, there has been a significant shift towards microorganism-based ARA production. To accelerate large-scale ARA production, it is crucial to select suitable strains and establish optimal culture conditions., Results: Here, we isolated a novel microalga Lobosphaera incisa CFRC-1, a valuable strain that holds promise as a feedstock for ARA production. Optimal cultivation conditions were investigated using a high-throughput screening method to enhance ARA production in this novel strain. Out of 71 candidates, four organic carbon substrates were identified that could be utilized by L. incisa CFRC-1. Through flask-scale verification, fructose was confirmed as the optimal organic carbon substrate for promoting microalgal growth, total lipid accumulation, and ARA production. Subsequently, we investigated appropriate substrate concentration and cultivation temperature, confirming that the optimal conditions were 30 g L - 1 of fructose and 27 ℃ of temperature. Under these optimized conditions, biomass and ARA production reached 13.05 ± 0.40 g L - 1 and 97.98 ± 7.33 mg L - 1 , respectively, representing 9.6-fold and 5.3-fold increases compared to the conditions before optimization conditions. These results achieved the highest biomass and ARA production in flask-scale cultivation, indicating that our approach effectively improved both production titer and productivity., Conclusions: This study presents a novel microalgae and optimized conditions for enhancing biomass and ARA production, suggesting that this approach is a practical way to accelerate the production of valuable microalgae-based chemicals. These findings provide a basis for large-scale production of ARA-utilizing microalgae for industrial applications., (© 2024. The Author(s).)

Background: The impression section integrates key findings of a radiology report but can be subjective and variable. We sought to fine-tune and evaluate an open-source Large Language Model (LLM) in automatically generating impressions from the remainder of a radiology report across different imaging modalities and hospitals., Methods: In this institutional review board-approved retrospective study, we collated a dataset of CT, US, and MRI radiology reports from the University of California San Francisco Medical Center (UCSFMC) (n = 372,716) and the Zuckerberg San Francisco General (ZSFG) Hospital and Trauma Center (n = 60,049), both under a single institution. The Recall-Oriented Understudy for Gisting Evaluation (ROUGE) score, an automatic natural language evaluation metric that measures word overlap, was used for automatic natural language evaluation. A reader study with five cardiothoracic radiologists was performed to more strictly evaluate the model's performance on a specific modality (CT chest exams) with a radiologist subspecialist baseline. We stratified the results of the reader performance study based on the diagnosis category and the original impression length to gauge case complexity., Results: The LLM achieved ROUGE-L scores of 46.51, 44.2, and 50.96 on UCSFMC and upon external validation, ROUGE-L scores of 40.74, 37.89, and 24.61 on ZSFG across the CT, US, and MRI modalities respectively, implying a substantial degree of overlap between the model-generated impressions and impressions written by the subspecialist attending radiologists, but with a degree of degradation upon external validation. In our reader study, the model-generated impressions achieved overall mean scores of 3.56/4, 3.92/4, 3.37/4, 18.29 s,12.32 words, and 84 while the original impression written by a subspecialist radiologist achieved overall mean scores of 3.75/4, 3.87/4, 3.54/4, 12.2 s, 5.74 words, and 89 for clinical accuracy, grammatical accuracy, stylistic quality, edit time, edit distance, and ROUGE-L score respectively. The LLM achieved the highest clinical accuracy ratings for acute/emergent findings and on shorter impressions., Conclusions: An open-source fine-tuned LLM can generate impressions to a satisfactory level of clinical accuracy, grammatical accuracy, and stylistic quality. Our reader performance study demonstrates the potential of large language models in drafting radiology report impressions that can aid in streamlining radiologists' workflows., (© 2024. The Author(s).)

Background: Whole-genome sequencing (WGS) analyses have found higher genetic burden in autistic females compared to males, supporting higher liability threshold in females. However, genomic evidence of sex differences has been limited to European ancestry to date and little is known about how genetic variation leads to autism-related traits within families across sex., Methods: To address this gap, we present WGS data of Korean autism families (n = 2255) and a Korean general population sample (n = 2500), the largest WGS data of East Asian ancestry. We analyzed sex differences in genetic burden and compared with cohorts of European ancestry (n = 15,839). Further, with extensively collected family-wise Korean autism phenotype data (n = 3730), we investigated sex differences in phenotypic scores and gene-phenotype associations within family., Results: We observed robust female enrichment of de novo protein-truncating variants in autistic individuals across cohorts. However, sex differences in polygenic burden varied across cohorts and we found that the differential proportion of comorbid intellectual disability and severe autism symptoms mainly drove these variations. In siblings, males of autistic females exhibited the most severe social communication deficits. Female siblings exhibited lower phenotypic severity despite the higher polygenic burden than male siblings. Mothers also showed higher tolerance for polygenic burden than fathers, supporting higher liability threshold in females., Conclusions: Our findings indicate that genetic liability in autism is both sex- and phenotype-dependent, expanding the current understanding of autism's genetic complexity. Our work further suggests that family-based assessments of sex differences can help unravel underlying sex-differential liability in autism., (© 2024. The Author(s).)

Background: Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive., Methods: In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities., Results: We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy., Conclusions: Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients., (© 2024. The Author(s).)

Background: Early neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke., Methods: This study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile., Results: Among the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06-5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19-12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups., Conclusions: As a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban., (© 2024. The Author(s).)

Background: This study aimed to investigate the radiological changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) having bronchiolitis patterns on computed tomography (CT)., Methods: We retrospectively reviewed the final diagnosis and radiologic changes of patients suspected of having NTM-PD without cavity or bronchiectasis on CT image, between January 1, 2005 and March 31, 2021. NTM-PD was diagnosed based on the American Thoracic Society and Infectious Diseases Society of America criteria. The initial and final CT findings (bronchiectasis, cellular bronchiolitis, cavity formation, nodules, and consolidation) were compared between patients diagnosed with and without NTM-PD., Results: This study included 96 patients and 515 CT images. The median CT follow-up duration was 1510.5 (interquartile range: 862.2-3005) days. NTM-PD was recognized in 43 patients. The clinical variables were not significantly different between patients with and without NTM-PD, except for underlying chronic airway disease (P < 0.001). Nodule and consolidation were more frequently observed on the initial CT scans of patients with NTM-PD compared with those without (P < 0.05). On the final follow-up CT scan, bronchiectasis (P < 0.001), cavity (P < 0.05), nodule (P < 0.05), and consolidation (P < 0.05) were more frequently observed in patients with NTM-PD. Among the 43 patients with NTM-PD, 30 showed a radiological progression on CT, with bronchiectasis (n = 22) being the most common finding. The incidence of bronchiectasis increased over time., Conclusion: The bronchiolitis pattern on CT images of patients with NTM-PD showed frequent radiological progression during the follow-up period., (© 2024. The Author(s).)

Background: The demand for organ transplants, both globally and in South Korea, substantially exceeds the supply, a situation that might have been aggravated by the enactment of the Life-Sustaining Treatment Decision Act (LSTDA) in February 2018. This legislation may influence emergency medical procedures and the availability of organs from brain-dead donors. This study aimed to assess LSTDA's impact, introduced in February 2018, on organ donation status in out-of-hospital cardiac arrest (OHCA) patients in a metropolitan city and identified related factors., Methods: We conducted a retrospective analysis of a regional cardiac arrest registry. This study included patients aged 16 or older with cardiac arrest and a cerebral performance category (CPC) score of 5 from January 2015 to December 2022. The exclusion criteria were CPC scores of 1-4, patients under 16 years, and patients declared dead or transferred from emergency departments. Logistic regression analysis was used to analyse factors affecting organ donation., Results: Of the 751 patients included in this study, 47 were organ donors, with a median age of 47 years. Before the LSTDA, there were 30 organ donations, which declined to 17 after its implementation. In the organ donation group, the causes of cardiac arrest included medical (34%), hanging (46.8%), and trauma (19.2%). The adjusted odds ratio for organ donation before the LSTDA implementation was 6.12 (95% CI 3.09-12.12), with non-medical aetiology as associated factors., Conclusion: The enactment of the LSTDA in 2018 in South Korea may be linked to reduced organ donations among patients with OHCA, underscoring the need to re-evaluate the medical and legal aspects of organ donation, especially considering end-of-life care decisions., (© 2024. The Author(s).)

Background: Previous studies have consistently reported a decrease in hospital admissions for respiratory diseases during the coronavirus disease 2019 (COVID-19) pandemic. However, the impact of the pandemic on idiopathic pulmonary fibrosis (IPF) admissions remains unknown., Methods: This study used data from the Korean National Health Insurance Service database. IPF was defined based on the International Classification of Diseases 10th Revision (ICD-10) and rare intractable disease (RID) codes. The rate of IPF admissions was calculated by dividing the number of IPF admissions by the prevalence of IPF. The rate of IPF admissions during the COVID-19 pandemic (2020-2021) was compared with the mean rate of admissions during the prepandemic period (2017-2019) and presented as the rate ratio (RR). A sensitivity analysis was conducted on patients treated with systemic corticosteroids during IPF admission., Results: In patients with IPF defined based on the ICD-10 (analysis 1), the RRs significantly decreased from March in 2020 to December 2021, except for June and September in 2020. Similarly, in patients with IPF defined based on the ICD-10 and RID (analysis 2), the RRs significantly decreased from March 2020 to December 2021, except for June and September 2020. In the sensitivity analysis of analysis 1, the RR significantly decreased in 2020 (0.93; 95%CI: 0.88-0.99; P = 0.029), whereas the RR in 2021 was not significantly different. The RRs in the sensitivity analysis of analysis 2 significantly decreased to 0.85 (0.79-0.92; P < 0.001) in 2020 and 0.82 (0.76-0.88; P < 0.001) in 2021. In the subgroup analysis, the rates of IPF admissions significantly decreased in 2020 and 2021 across both sexes, patients aged ≥ 60 years, and all household income groups., Conclusions: The rate of IPF admissions significantly decreased during the COVID-19 pandemic. This result indicates that preventive measures against COVID-19 may effectively mitigate IPF exacerbation. Therefore, it is assumed that there is a close relationship between respiratory viral infections and IPF exacerbations., (© 2024. The Author(s).)

Background: This study aimed to evaluate the femoral tunnel position and fiber length of the anterolateral ligament (ALL) reconstruction compared with the natural anatomy of the ALL. We also evaluated whether the femoral tunnel position would affect residual pivot shift., Methods: This study was a retrospective review of 55 knees that underwent ALL reconstruction considering the anatomical and functional aspects, during primary anterior cruciate ligament (ACL) reconstruction in the presence of a high-grade pivot shift or revisional ACL reconstruction. We determined the position of the femoral tunnel and the length of graft using a three-dimensional (3D)-computed tomography (CT) model after ALL reconstruction. We also measured graft excursion during surgery and examined pivot shift 2 years after surgery. We conducted a subgroup analysis of femoral tunnel position, fiber length, isometricity, and residual pivot shift depending on whether the tunnel was anterior or posterior to the lateral epicondyle (LE). We also performed a subgroup analysis depending on whether the ACL reconstruction was primary or revisional., Results: The mean femoral tunnel position was 2.04 mm posterior and 14.5 mm proximal from the center of the LE. The mean lengths of the anterior and posterior fibers were 66.6 and 63.4 mm, respectively. The femoral tunnel was positioned more proximally than the anatomical position, and both anterior and posterior ALL fibers were longer than the natural anatomy. The anteroposterior femoral tunnel position was significantly correlated with anterior (p = 0.045) and posterior (p = 0.037) fiber excursion. In the subgroup analysis, there was no significant difference in the residual pivot shift between the posterior and anterior tunnel positions. However, there were significant differences for proximal position (p < 0.001) and fiber length (p = 0.006). There was no significant difference between primary and revisional ACL regarding femoral tunnel position and fiber lengths., Conclusion: It is challenging to reproduce both anatomical and functional aspects of ALL reconstruction in both primary and revision ACL reconstruction. Especially for functional reconstruction, the femoral tunnel tended to be positioned more proximally than the anatomical position. However, the femoral tunnel position did not affect functional clinical outcomes at the 2-year follow-up., Level of Evidence: Level IV Case series., (© 2024. The Author(s).)

Background: Despite the well-known health benefits of exercise, women's participation in exercise is low worldwide. As women are at risk of developing various chronic diseases as they age, suggesting effective exercise methods that can maximize energy consumption is needed to prevent such conditions. Excess post-exercise oxygen consumption (EPOC) can maximize energy consumption. In this crossover, randomized controlled trial, we aimed to compare the EPOC for different exercise modalities including continuous exercise (CE), interval exercise (IE), and accumulated exercise (AE) that spent the homogenized energy expenditure during exercise in healthy women., Methods: Forty-four participants (age, 36.09 ± 11.73 years) were recruited and randomly allocated to three groups. The intensity of each modality was set as follows: CE was performed for 30 min at 60% peak oxygen uptake (VO 2 peak). IE was performed once for 2 min at 80% VO 2 peak, followed by 3 min at 80% VO 2 peak, and 1 min at 40% VO 2 peak, for a total of six times over 26 min. AE was performed for 10 min with a 60% VO 2 peak and was measured thrice a day., Results: During exercise, energy metabolism was higher for IE and CE than that for AE. However, this was reversed for AE during EPOC. Consequently, the greatest energy metabolism was shown for AE during total time (exercise and EPOC)., Conclusions: By encouraging regular exercises, AE can help maintain and improve body composition by increasing compliance with exercise participation, given its short exercise times, and by efficiently increasing energy consumption through the accumulation of EPOC., Trial Registration: Clinical number (KCT0007298), 18/05/2022, Institutional Review Board of Konkuk University (7001355-202201-E-160)., (© 2024. The Author(s).)

Background: This study aimed to determine the 50% effective dose of remimazolam co-administered with remifentanil for loss of consciousness in men and women as well as to investigate whether there are between-sex differences., Methods: Using a modified Dixon's up-and-down allocation approach, we sequentially enrolled male and female patients aged 19-60 years with American Society of Anesthesiologists class I or II who were scheduled for robotic surgery. For both sexes, the starting remimazolam dose was 0.15 mg/kg, with a step size of 0.05 mg/kg. After achievement of a target effect-site concentration 2.0 ng/ml of remifentanil, and administration of a bolus dose of remimazolam, we assessed whether adequate loss of consciousness (defined as a Modified Observer's Assessment of Alertness/Sedation scale score < 2 within 2 min) was achieved., Results: We included 22 male and 22 female patients. Based on Dixon's up-and-down method, the 50% effective dose of remimazolam (mean ± standard error) was 0.13 ± 0.01 mg/kg and 0.17 ± 0.01 mg/kg in the male and female groups, respectively (P = 0.34). Isotonic regression analysis revealed that the 95% effective dose (95% confidence interval) was 0.19 (0.18-0.20) mg/kg in the male group and 0.29 (0.29-0.30) mg/kg in the female group., Conclusions: There was no between-sex difference in the 50% effective dose of remimazolam for loss of consciousness; however, the 95% effective dose was significantly higher in female patients than in male patients., Trial Registration: This study protocol was registered at Clinical Research Information Service (CRIS No. KCT0007951, 02/12/2022)., (© 2024. The Author(s).)

Background: Mixed reality (MR) is helpful in hand training for patients with stroke, allowing them to fully submerge in a virtual space while interacting with real objects. The recognition of individual finger movements is required for MR rehabilitation. This study aimed to assess the effectiveness of updated MR-board 2, adding finger training for patients with stroke., Methods: Twenty-one participants with hemiplegic stroke (10 with left hemiplegia and 11 with right hemiplegia; nine female patients; 56.7 ± 14.2 years of age; and onset of stroke 32.7 ± 34.8 months) participated in this study. MR-board 2 comprised a board plate, a depth camera, plastic-shaped objects, a monitor, a palm-worn camera, and seven gamified training programs. All participants performed 20 self-training sessions involving 30-min training using MR-board 2. The outcome measurements for upper extremity function were the Fugl-Meyer assessment (FMA) upper extremity score, repeated number of finger flexion and extension (Repeat-FE), the thumb opposition test (TOT), Box and Block Test score (BBT), Wolf Motor Function Test score (WMFT), and Stroke Impact Scale (SIS). One-way repeated measures analysis of variance and the post hoc test were applied for the measurements. MR-board 2 recorded the fingers' active range of motion (AROM) and Dunnett's test was used for pairwise comparisons., Results: Except for the FMA-proximal score (p = 0.617) and TOT (p = 0.005), other FMA scores, BBT score, Repeat-FE, WMFT score, and SIS stroke recovery improved significantly (p < 0.001) during MR-board 2 training and were maintained until follow-up. All AROM values of the finger joints changed significantly during training (p < 0.001)., Conclusions: MR-board 2 self-training, which includes natural interactions between humans and computers using a tangible user interface and real-time tracking of the fingers, improved upper limb function across impairment, activity, and participation. MR-board 2 could be used as a self-training tool for patients with stroke, improving their quality of life., Trial Registration Number: This study was registered with the Clinical Research Information Service (CRIS: KCT0004167)., (© 2024. The Author(s).)

Background: To identify longitudinal changes in each retinal layer thickness in central retinal vein occlusion (CRVO) patients with resolved macular edema (ME)., Methods: In this retrospective observational study, CRVO patients without a recurrence of ME for more than 3 years and normal controls were enrolled. Each retinal layer thickness of the parafoveal area, including ganglion cell complex (GCC), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor layer (PRL), and retinal pigment epithelium (RPE) was measured. After the resolution of ME, three more examinations with a 1-year interval were analyzed., Results: A total of 98 eyes were enrolled, 50 eyes for the control group and 48 eyes for the CRVO group. The baseline GCC thickness was 114.2 ± 15.6 μm and 104.2 ± 25.4 μm in the control and CRVO groups, respectively, which was significantly different (P = 0.022). The thicknesses of other layers including INL, OPL, ONL, PRL, and RPE were not significantly different at baseline. The reduction rate of GCC, INL, OPL, and ONL was - 3.92, - 1.33, - 0.91, and - 2.31 μm/year in the CRVO group, whereas no significant reductions were observed in the control group. Best-corrected visual acuity was significantly associated with changes in the GCC, OPL, and ONL in the CRVO group., Conclusions: In patients with CRVO, even in the absence of recurrent ME, retinal damage progresses over time, evidenced by thinning of the inner retina and outer retina including OPL and ONL. These changes may be associated with alterations in visual function., (© 2024. The Author(s).)

Background Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are found in 1% of gliomas across children and adults. TRK inhibitors are promising therapeutic agents for NTRK-fused gliomas because they are tissue agnostic and cross the blood-brain barrier (BBB). Methods We investigated twelve NGS-verified NTRK-fused gliomas from a single institute, Seoul National University Hospital. Results The patient cohort included six children (aged 1-15 years) and six adults (aged 27-72 years). NTRK2 fusions were found in ten cerebral diffuse low-grade and high-grade gliomas (DLGGs and DHGGs, respectively), and NTRK1 fusions were found in one cerebral desmoplastic infantile ganglioglioma and one spinal DHGG. In this series, the fusion partners of NTRK2 were HOOK3, KIF5A, GKAP1, LHFPL3, SLMAP, ZBTB43, SPECC1L, FKBP15, KANK1, and BCR, while the NTRK1 fusion partners were TPR and TPM3. DLGGs tended to harbour only an NTRK fusion, while DHGGs exhibited further genetic alterations, such as TERT promoter/TP53/PTEN mutation, CDKN2A/2B homozygous deletion, PDGFRA/KIT/MDM4/AKT3 amplification, or multiple chromosomal copy number aberrations. Four patients received adjuvant TRK inhibitor therapy (larotrectinib, repotrectinib, or entrectinib), among which three also received chemotherapy (n = 2) or proton therapy (n = 1). The treatment outcomes for patients receiving TRK inhibitors varied: one child who received larotrectinib for residual DLGG maintained stable disease. In contrast, another child with DHGG in the spinal cord experienced multiple instances of tumour recurrence. Despite treatment with larotrectinib, ultimately, the child died as a result of tumour progression. An adult patient with glioblastoma (GBM) treated with entrectinib also experienced tumour progression and eventually died. However, there was a successful outcome for a paediatric patient with DHGG who, after a second gross total tumour removal followed by repotrectinib treatment, showed no evidence of disease. This patient had previously experienced relapse after the initial surgery and underwent autologous peripheral blood stem cell therapy with carboplatin/thiotepa and proton therapy. Conclusions Our study clarifies the distinct differences in the pathology and TRK inhibitor response between LGG and HGG with NTRK fusions., (© 2024. The Author(s).)

Background: Follicular lymphoma (FL) is characterized by t(14;18)(q32;q21) involving the IGH and BCL2 genes. However, 10-15% of FLs lack the BCL2 rearrangement. These BCL2-rearrangement-negative FLs are clinically, pathologically, and genetically heterogeneous. The biological behavior and histological transformation of such FLs are not adequately characterized. Here, we report the first case of t(14;18)-negative FL that rapidly progressed to plasmablastic lymphoma (PBL)., Case Presentation: A previously healthy 51-year-old man presented with leg swelling. Computed tomography (CT) showed enlarged lymph nodes (LNs) throughout the body, including both inguinal areas. Needle biopsy of an inguinal LN suggested low-grade B-cell non-Hodgkin lymphoma. Excisional biopsy of a neck LN showed proliferation of centrocytic and centroblastic cells with follicular and diffuse growth patterns. Immunohistochemical analysis showed that the cells were positive for CD20, BCL6, CD10, and CD23. BCL2 staining was negative in the follicles and weak to moderately positive in the interfollicular areas. BCL2 fluorescence in situ hybridization result was negative. Targeted next-generation sequencing (NGS) revealed mutations in the TNFRSF14, CREBBP, STAT6, BCL6, CD79B, CD79A, and KLHL6 genes, without evidence of BCL2 or BCL6 rearrangement. The pathologic and genetic features were consistent with t(14;18)-negative FL. Two months after one cycle of bendamustine and rituximab chemotherapy, the patient developed left flank pain. Positron emission tomography/CT showed new development of a large hypermetabolic mass in the retroperitoneum. Needle biopsy of the retroperitoneal mass demonstrated diffuse proliferation of large plasmablastic cells, which were negative for the B-cell markers, BCL2, BCL6, and CD10; they were positive for MUM-1, CD138, CD38, and C-MYC. The pathologic findings were consistent with PBL. The clonal relationship between the initial FL and subsequent PBL was analyzed via targeted NGS. The tumors shared the same CREBBP, STAT6, BCL6, and CD79B mutations, strongly suggesting that the PBL had transformed from a FL clone. The PBL also harbored BRAF V600E mutation and IGH::MYC fusion in addition to IGH::IRF4 fusion., Conclusions: We propose that transformation or divergent clonal evolution of FL into PBL can occur when relevant genetic mutations are present. This study broadens the spectrum of histological transformation of t(14;18)-negative FL and emphasizes its biological and clinical heterogeneity., (© 2024. The Author(s).)

Aminopyrrolnitrin (APRN), a natural halogenated phenylpyrrole derivative (HPD), has strong antifungal and antiparasitic activities. Additionally, it showed 2.8-fold increased photostability compared to pyrrolnitrin, a commercially available HPD with antimicrobial activity. For microbial production of APRN, we first engineered anthranilate phosphoribosyltransferase encoded by trpD from Corynebacterium glutamicum, resulting in a TrpD A162D mutation that exhibits feedback-resistant against L-tryptophan and higher substrate affinity compared to wild-type TrpD. Plasmid-borne expression of trpD A162D in C. glutamicum TP851 strain with two copies of trpD A162D in the genome led to the production of 3.1 g/L L-tryptophan in flask culture. Subsequent step for L-tryptophan chlorination into 7-chloro-L-tryptophan was achieved by introducing diverse sources of genes encoding tryptophan 7-halogenase (PrnA or RebH) and flavin reductase (Fre, PrnF, or RebF). The combined expression of prnA from Serratia grimesii or Serratia plymuthica with flavin reductase gene from Escherichia coli, Pseudomonas fluorescens, or Lechevalieria aerocolonigenes yielded higher production of 7-chloro-L-tryptophan in comparison to other sets of two-component systems. In the next step, production of putative monodechloroaminopyrrolnitrin (MDAP) from 7-chloro-L-tryptophan was achieved through the expression of prnB encoding MDAP synthase from S. plymuthica or P. fluorescens. Finally, an artificial APRN biosynthetic pathway was constructed by simultaneously expressing genes coding for tryptophan 7-halogenase, flavin reductase, MDAP synthase, and MDAP halogenase (PrnC) from different microbial sources within the L-tryptophan-producing TP851 strain. As prnC from S. grimesii or S. plymuthica was introduced into the host strain, which carried plasmids expressing prnA from S. plymuthica, fre from E. coli, and prnB from S. plymuthica, APN3639 and APN3638 accumulated 29.5 mg/L and 28.1 mg/L of APRN in the culture broth. This study represents the first report on the fermentative APRN production by metabolically engineered C. glutamicum., (© 2024. The Author(s).)

Background: Basal cell adenoma (BCA) is a rare benign tumor within the salivary glands. Basal cell adenocarcinoma (BCAC), the malignant counterpart of BCA, is also an exceedingly rare tumor with very limited clinical studies conducted. This study aims to investigate the clinical characteristics, demographics, and surgical outcomes of patients diagnosed with BCA and BCAC within the parotid gland., Methods: A retrospective analysis from May 2003 to August 2023 was performed for all patients undergoing parotidectomy for masses. Retrospective data on gender, age, tumor characteristics, and outcomes were collected. Surgical approaches, including negative margin attainment, capsule removal, and histological diagnosis, were also detailed., Results: The study included 1268 patients who underwent parotidectomy, resulting in 81 cases of BCA and 7 cases of BCAC. BCA patients, with a mean age of 55.1 years, showed diverse age distribution and predominantly presented in the 50s. In BCAC cases, seven female patients exhibited a predominant location in the deep lobes. FNA revealed BCAC in three out of seven cases, and subsequent parotidectomy was performed, resulting in no observed recurrences or metastases., Conclusion: This study reports the largest number of BCA cases from a single institution and provides comprehensive insights into the demographics, tumor characteristics, and clinical outcomes of both BCA and BCAC. Although further research should be conducted, based on clinical follow-up results, appropriately including the capsule in the tumor excision indicates favorable outcomes, especially when the tumor size is not large., (© 2024. The Author(s).)

Nonviral delivery of the CRISPR/Cas9 system provides great benefits for in vivo gene therapy due to the low risk of side effects. However, in vivo gene editing by delivering the Cas9 ribonucleoprotein (RNP) is challenging due to the poor delivery into target tissues and cells. Here, we introduce an effective delivery method for the CRISPR/Cas9 RNPs by finely tuning the formulation of ionizable lipid nanoparticles. The LNPs delivering CRISPR/Cas9 RNPs (CrLNPs) are demonstrated to induce gene editing with high efficiencies in various cancer cell lines in vitro. Furthermore, we show that CrLNPs can be delivered into tumor tissues with high efficiency, as well as induce significant gene editing in vivo. The current study presents an effective platform for nonviral delivery of the CRISPR/Cas9 system that can be applied as an in vivo gene editing therapeutic for treating various diseases such as cancer and genetic disorders., (© 2024. The Author(s).)

Proteus mirabilis is a commensal bacterium dwelling in the gastrointestinal (GI) tract of humans and animals. Although New Delhi metallo-β-lactamase 1 (NDM-1) producing P. mirabilis is emerging as a threat, its epidemiology in our society remains largely unknown. LHPm1, the first P. mirabilis isolate harboring NDM-1, was detected from a companion dog that resides with a human owner. The whole-genome study revealed 20 different antimicrobial resistance (AMR) genes against various classes of antimicrobial agents, which corresponded to the MIC results. Genomic regions, including MDR genes, were identified with multiple variations and visualized in a comparative manner. In the whole-genome epidemiological analysis, multiple phylogroups were identified, revealing the genetic relationship of LHPm1 with other P. mirabilis strains carrying various AMR genes. These genetic findings offer comprehensive insights into NDM-1-producing P. mirabilis, underscoring the need for urgent control measures and surveillance programs using a "one health approach"., (© 2024. The Author(s).)

ABSTRACT: BACKGROUND: Clonorchis sinensis infection is one of the risk factors that provokes chronic inflammation, epithelial hyperplasia, periductal fibrosis and even cholangiocarcinoma (CCA). Disrupted or aberrant intercellular communication among liver-constituting cells leads to pathological states that cause various hepatic diseases. This study was designed to investigate the pathological changes caused by C. sinensis excretory-secretory products (ESPs) in non-cancerous human cell lines (cholangiocytes [H69 cell line] and human hepatic stellate cells [LX2 cell line]) and their intercellular crosstalk, as well the pathological changes in infected mouse liver tissues., Methods: The cells were treated with ESPs, following which transforming growth factor beta 1 (TGF-β1) and interleukin-6 (IL-6) secretion levels and epithelial-mesenchymal transition (EMT)- and fibrosis-related protein expression were measured. The ESP-mediated cellular motility (migration/invasion) between two cells was assessed using the Transwell and three-dimensional microfluidic assay models. The livers of C. sinensis-infected mice were stained using EMT and fibrotic marker proteins., Results: Treatment of cells with ESPs increased TGF-β1 and IL-6 secretion and the expression of EMT- and fibrosis-related proteins. The ESP-mediated mutual cell interaction further affected the cytokine secretion and protein expression levels and promoted cellular motility. N-cadherin overexpression and collagen fiber deposition were observed in the livers of C. sinensis-infected mice., Conclusions: These findings suggest that EMT and biliary fibrosis occur through intercellular communication between cholangiocytes and hepatic stellate cells during C. sinensis infection, promoting malignant transformation and advanced hepatobiliary abnormalities., (© 2024. The Author(s).)

Background: Perceiving oneself as obese has been associated with weight loss attempts. However, such a perception may not sufficiently drive significant weight reduction in many individuals. Hence, relying solely on the traditionally emphasized perceived risk of behavioral changes in obesity is challenging. This study used an extended parallel process model and a risk perception attitude framework to explore the influence of perceived risk and perceived efficacy on individual obesity knowledge and obesity prevention behaviors., Methods: Data were obtained from 1,100 Korean adults aged 40-69 years through an online survey conducted in October 2022. Multinomial logistic regression and analysis of variance were employed to assess the relationships among perceived risk, perceived efficacy, obesity knowledge, and obesity prevention behaviors., Results: Sex was associated with being underweight, overweight, and obese. Moreover, perceived severity was associated with obesity, whereas perceived susceptibility was associated with overweight and obese. Response efficacy was related to being overweight alone, whereas self-efficacy was associated with being underweight, overweight, and obese. The main effects of sex and perceived risk, and their interaction effect were statistically significant for obesity knowledge. Additionally, the main effects of sex, perceived risk, and perceived efficacy on obesity prevention behaviors were statistically significant., Conclusions: The extended parallel process model and risk perception attitude framework proved effective in classifying obesity based on body mass index, obesity knowledge, and obesity prevention behaviors., (© 2024. The Author(s).)

Background: Immunotherapy is applied to breast cancer to resolve the limitations of survival gain in existing treatment modalities. With immunotherapy, a tumor can be classified into immune-inflamed, excluded and desert based on the distribution of immune cells. We assessed the clinicopathological features, each subtype's prognostic value and differentially expressed proteins between immune subtypes., Methods: Immune subtyping and proteomic analysis were performed on 56 breast cancer cases with neoadjuvant chemotherapy. The immune subtyping was based on the level of tumor-infiltrating lymphocytes (TILs) and Klintrup criteria. If the level of TILs was ≥ 10%, it was classified as immune-inflamed type without consideration of the Klintrup criteria. In cases of 1-9% TIL, Klintrup criteria 1-3 were classified as the immune-excluded subtype and Klintrup criteria not available (NA) was classified as NA. Cases of 1% TILs and Klintrup 0 were classified as the immune-desert subtype. Mass spectrometry was used to identify differentially expressed proteins in formalin-fixed paraffin-embedded biopsy tissues., Results: Of the 56 cases, 31 (55%) were immune-inflamed, 21 (38%) were immune-excluded, 2 (4%) were immune-desert and 2 (4%) were NA. Welch's t-test revealed two differentially expressed proteins between immune-inflamed and immune-excluded/desert subtypes. Coronin-1A was upregulated in immune-inflamed tumors (adjusted p = 0.008) and α-1-antitrypsin was upregulated in immune-excluded/desert tumors (adjusted p = 0.008). Titin was upregulated in pathologic complete response (pCR) than non-pCR among immune-inflamed tumors (adjusted p = 0.036)., Conclusions: Coronin-1A and α-1-antitrypsin were upregulated in immune-inflamed and immune-excluded/desert subtypes, respectively. Titin's elevated expression in pCR within the immune-inflamed subtype may indicate a favorable prognosis. Further studies involving large representative cohorts are necessary to validate these findings., (© 2024. The Author(s).)

Background: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC., Methods: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan)., Results: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy., Conclusions: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression., Trial Registration: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732)., (© 2024. The Author(s).)

Background: Ulinastatin, an anti-inflammatory and antioxidant trypsin inhibitor, has shown potential in mitigating acute kidney injury (AKI) and reducing serum creatinine levels after various surgeries. This retrospective study aimed to evaluate the effects of ulinastatin on AKI in patients undergoing off-pump coronary artery bypass (OPCAB) surgery., Methods: We hypothesized that the administration of ulinastatin could prevent AKI in OPCAB. Electrical medical records were reviewed to identify OPCAB patients between January 2015 and June 2020. The utilization of ulinastatin was randomly determined and applied during this period. Acute kidney injury was defined according to the KDIGO guideline, and its incidence was compared between the ulinastatin administration group and the control group. To investigate the effect of ulinastatin on renal function, multivariate logistic regression analysis was used to calculate propensity scores for each group., Results: A total 454 OPCAB were performed, and after following inclusion and exclusion process, 100 patients were identified in the ulinastatin group and 303 patients in the control group. Using 1:2 propensity score matching, we analyzed 100 and 200 patients in the ulinastatin and control groups. The incidence of AKI was similar between the groups (2.5% for the control group, 2.0% for the ulinastatin group, p > 0.999). However, the serum creatinine value on the first post-operative day were significantly lower in the ulinastatin group compared to the control group (0.774 ± 0.179 mg/dL vs 0.823 ± 0.216 mg/dL, P = 0.040), while no significant differences were observed for the other time points (P > 0.05). The length of ICU stay day was significantly shorter in the ulinastatin group (2.91 ± 2.81 day vs 5.22 ± 7.45 day, respectively, P < 0.001)., Conclusions: Ulinastatin did not have a significant effect on the incidence of AKI; it demonstrated the ability to reduce post-operative serum creatine levels at first post-operative day and shorten the length of ICU stay., (© 2024. Crown.)

Background: Oral potentially malignant disorders (OPMDs) are associated with an increased risk of cancer of the oral cavity including the tongue. The early detection of oral cavity cancers and OPMDs is critical for reducing cancer-specific morbidity and mortality. Recently, there have been studies to apply the rapidly advancing technology of deep learning for diagnosing oral cavity cancer and OPMDs. However, several challenging issues such as class imbalance must be resolved to effectively train a deep learning model for medical imaging classification tasks. The aim of this study is to evaluate a new technique of artificial intelligence to improve the classification performance in an imbalanced tongue lesion dataset., Methods: A total of 1,810 tongue images were used for the classification. The class-imbalanced dataset consisted of 372 instances of cancer, 141 instances of OPMDs, and 1,297 instances of noncancerous lesions. The EfficientNet model was used as the feature extraction model for classification. Mosaic data augmentation, soft labeling, and curriculum learning (CL) were employed to improve the classification performance of the convolutional neural network., Results: Utilizing a mosaic-augmented dataset in conjunction with CL, the final model achieved an accuracy rate of 0.9444, surpassing conventional oversampling and weight balancing methods. The relative precision improvement rate for the minority class OPMD was 21.2%, while the relative [Formula: see text] score improvement rate of OPMD was 4.9%., Conclusions: The present study demonstrates that the integration of mosaic-based soft labeling and curriculum learning improves the classification performance of tongue lesions compared to previous methods, establishing a foundation for future research on effectively learning from imbalanced data., (© 2024. The Author(s).)

Background: Inflammation is a major pathological mechanism underlying cerebrovascular disease. Recently, a new inflammatory marker based on the ratio between monocyte count and high-density lipoprotein (HDL) cholesterol has been proposed. In this study, we evaluated the relationship between monocyte-to-HDL cholesterol ratio (MHR) and cerebral small vessel disease (cSVD) lesions in health check-up participants., Methods: This study was a retrospective cross-sectional study based on a registry that prospectively collected health check-up participants between 2006 and 2013. Three cSVD subtypes were measured on brain magnetic resonance imaging. White matter hyperintensity (WMH) volume, and lacunes and cerebral microbleeds (CMBs) were quantitatively and qualitatively measured, respectively. The MHR was calculated according to the following formula: MHR = monocyte counts (× 10 3 /μL) / HDL cholesterol (mmol/L)., Results: In total, 3,144 participants were evaluated (mean age: 56 years, male sex: 53.9%). In multivariable analyzes adjusting for confounders, MHR was significantly associated with WMH volume [β = 0.099, 95% confidence interval (CI) = 0.025 to 0.174], lacune [adjusted odds ratio (aOR) = 1.43, 95% CI = 1.07-1.91], and CMB (aOR = 1.51, 95% CI = 1.03-2.19). In addition, MHR showed a positive quantitative relationship with cSVD burden across all three subtypes: WMH (P < 0.001), lacunes (P < 0.001), and CMBs (P < 0.001)., Conclusions: High MHR was closely associated with cSVD in health check-up participants. Because these associations appear across all cSVD subtypes, inflammation appears to be a major pathological mechanism in the development of various cSVDs., (© 2024. The Author(s).)

Background: Crocin, a glycosylated apocarotenoid pigment predominantly found in saffron, has garnered significant interest in the field of biotechnology for its bioactive properties. Traditional production of crocins and their aglycone, crocetin, typically involves extraction from crocin-producing plants. This study aimed to develop an alternative biosynthetic method for these compounds by engineering the metabolic pathways of zeaxanthin, crocetin, and crocin in Escherichia coli strains., Results: Employing a series of genetic modifications and the strategic overexpression of key enzymes, we successfully established a complete microbial pathway for synthesizing crocetin and four glycosylated derivatives of crocetin, utilizing glycerol as the primary carbon source. The overexpression of zeaxanthin cleavage dioxygenase and a novel variant of crocetin dialdehyde dehydrogenase resulted in a notable yield of crocetin (34.77 ± 1.03 mg/L). Further optimization involved the overexpression of new types of crocetin and crocin-2 glycosyltransferases, facilitating the production of crocin-1 (6.29 ± 0.19 mg/L), crocin-2 (5.29 ± 0.24 mg/L), crocin-3 (1.48 ± 0.10 mg/L), and crocin-4 (2.72 ± 0.13 mg/L)., Conclusions: This investigation introduces a pioneering and integrated microbial synthesis method for generating crocin and its derivatives, employing glycerol as a sustainable carbon feedstock. The substantial yields achieved highlight the commercial potential of microbial-derived crocins as an eco-friendly alternative to plant extraction methods. The development of these microbial processes not only broadens the scope for crocin production but also suggests significant implications for the exploitation of bioengineered compounds in pharmaceutical and food industries., (© 2023. The Author(s).)

Background: Petersen's hernia, which occurs after Billroth-II (B-II) or Roux-en-Y (REY) anastomosis, can be reduced by defect closure. This study aims to compare the incidence of bowel obstruction above Clavien-Dindo classification grade III due to Petersen's hernia between the mesenteric fixation method and the conventional methods after laparoscopic or robotic gastrectomy., Methods: This study was designed as prospective, single-blind, non-inferiority randomized controlled multicenter trial in Korea. Patients with histologically diagnosed gastric cancer of clinical stages I, II, or III who underwent B-II or REY anastomosis after laparoscopic or robotic gastrectomy are enrolled in this study. Participants who meet the inclusion criteria are randomly assigned to two groups: a CLOSURE group that underwent conventional Petersen's defect closure method and a MEFIX group that underwent the mesenteric fixation method. The primary endpoint is the number of patients who underwent surgery for bowel obstruction caused by Petersen's hernia within 3 years after laparoscopic or robotic gastrectomy., Discussion: This trial is expected to provide high-level evidence showing that the MEFIX method can quickly and easily close Petersen's defect without increased postoperative complications compared to the conventional method., Trial Registration: ClinicalTrials.gov NCT05105360. Registered on November 3, 2021., (© 2023. The Author(s).)

Background: Bacterial colonization is an essential aspect of bronchiectasis. Although Haemophilus influenzae is a frequent colonizer in some regions, its clinical impacts are poorly understood. This study aimed to elucidate the impact of H. influenzae colonization in patients with bronchiectasis., Methods: This retrospective study screened adult patients diagnosed with bronchiectasis at a tertiary referral center between April 1, 2003, and May 16, 2021, in South Korea. Propensity score matching was used to match patients with and without H. influenzae colonization. We assessed the severity of bronchiectasis as per the bronchiectasis severity index, the incidence of exacerbation, differences in lung function, and all-cause mortality., Results: Out of the 4,453 patients with bronchiectasis, 79 (1.8%) were colonized by H. influenzae. After 1:2 propensity score matching, 78 and 154 patients were selected from the H. influenzae colonizer and non-colonizer groups, respectively. Although there were no significant differences between the groups regarding baseline demographics, patients colonized with H. influenzae had a higher bronchiectasis severity index (median 6 [interquartile range 4-8] vs. 4 [2-7], p = 0.002), associated with extensive radiographic involvement (52.2% vs. 37.2%, p = 0.045) and mild exacerbation without hospitalization (adjusted incidence rate ratio 0.15; 95% confidence interval 0.12-0.24). Lung function and mortality rates did not reveal significant differences, regardless of H. influenzae colonization., Conclusion: H. influenzae colonization in bronchiectasis was associated with more severe disease and greater incidence of mild exacerbation, but not lung function and mortality. Attention should be paid to patients with bronchiectasis with H. influenzae colonization., (© 2023. The Author(s).)

Background: The prevalence of anxiety among patients undergoing arthroscopic surgery and its association with postoperative function has been well documented; however, the level of anxiety and anxiety-related characteristics remain unclear. As such, the present study investigated the characteristics of state anxiety in patients undergoing arthroscopic meniscectomy., Methods: Data from 75 patients, who underwent arthroscopic partial meniscectomy under general anesthesia and completed an anxiety status questionnaire between April 2021 and March 2022, were retrospectively collected and reviewed. The State-Trait Anxiety Inventory (STAI)-X was used to measure state anxiety; a total score ≥ 52 was defined as clinically meaningful state anxiety. STAI score, main cause of preoperative anxiety, most anxious period, and most helpful factors for reducing perioperative anxiety were investigated. Patients were divided into 2 groups according to the main cause of preoperative anxiety; surgery or anesthesia (group I [n = 47]); and postoperative pain or rehabilitation (group II [n = 28]) Characteristics of state-anxiety between the two groups were compared using independent t-tests., Results: The mean STAI score of the total population was 39.1 points (range, 20-60 points). The mean STAI score was significantly higher in group I than in group II (41.9 vs. 34.4 points, respectively; P < 0.001). The proportion of patients with clinically meaningful state anxiety was significantly higher in group I than in group II (23.4% vs. 3.6%, respectively, P = 0.02). Most patients (66.0% in group I and 50.0% in group II) responded that trust in medical staff was the most helpful factor in overcoming preoperative anxiety. In group I, 63.8% reported that the surgeon's explanation was the most helpful factor in reducing postoperative anxiety, whereas in group II, 71.4% reported that the natural course after surgery was the most helpful factor., Conclusions: Surgeons should be aware that anxiety related to arthroscopic meniscectomy differs according to patient characteristics, and a preoperative explanation of the postoperative process with the surgeon is important for patients who experience preoperative anxiety regarding anesthesia or the surgery itself., (© 2023. The Author(s).)

Background: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE)., Methods: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups., Results: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups., Conclusions: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD., Trial Registration: NCT04080726 ( https://classic., Clinicaltrials: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018., (© 2023. The Author(s).)