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Ji Young Yoon,1 Keum-Jin Yang,2 Shi-Nae Park,3 Dong-Kee Kim,3 Jong-Duk Kim1 1Department of Chemical and Biomolecular Engineering, BK 21 Plus Program, Korea Advanced Institute of Science and Technology, Guseong-Dong, Yuseong-Gu, Daejeon, 2Clinical Research Institute, St Mary’s Hospital, Daejeon, 3Department of Otolaryngology – Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Abstract: Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells. This potential carrier co-delivering Dex and the gene into inner ear cells has a diameter of 120–140 nm and a zeta potential of 20–25 mV. Different types of genes were complexed with the Dex-loaded PCA nanoparticle (PCA/Dex/gene) for gene expression to induce additional anti-inflammatory effects. PCA/Dex showed mildly increased expression of GFP and lower mRNA expression of inflammatory cytokines (IL1b, IL12, and INFr) than did Dex-free PCA nanoparticles and Lipofectamine® reagent in HEI-OC1 cells. In addition, after loading Cx26 siRNA onto the surface of PCA/Dex, Cx26 gene expression was downregulated according to real-time polymerase chain reaction for 24 h, compared with that using Lipofectamine reagent. After loading BDNF DNA into PCA/Dex, increased expression of BDNF was observed for 30 h, and its signaling pathway resulted in an increase in phosphorylation of Akt, observed by Western blotting. Thus, Dex within PCA/Dex/gene nanoparticles created an anti-inflammatory effect and enhanced gene expression. Keywords: cell-penetrating peptide, nanoparticle, dexamethasone, gene delivery, brain-derived neurotrophic factor

Background: Percutaneous injection of bone cement (acrylic cement) during percutaneous kyphoplasty and vertebroplasty can cause symptomatic or asymptomatic complications due to leakage, extravasation or vascular migration of cement. Purpose: To investigate and to compare the incidence and site of local leakage or complications of bone cement after percutaneous kyphoplasty and vertebroplasty using bone cement. Material and Methods: We retrospectively reviewed 473 cases of percutaneous kyphoplasty or vertebroplasty performed under fluoroscopic guidance. Of the 473 cases, follow-up CT scans that covered the treated bones were available for 83 cases (59 kyphoplasty and 24 vertebroplasty). Results: The rate of local leakage of bone cement was 87.5% (21/24) for percutaneous vertebroplasty and 49.2% (29/59) for kyphoplasty. The most common site of local leakage was perivertebral soft tissue (n=8, 38.1%) for vertebroplasty. The most common site of local leakage was a perivertebral vein (n=7, 24.1%) for kyphoplasty. Two cases of pulmonary cement embolism developed: one case after kyphoplasty and one case after vertebroplasty. Conclusion: Local leakage of bone cement was more common for percutaneous vertebroplasty compared with kyphoplasty (P<0.005). The most common sites of local leakage were perivertebral soft tissue and perivertebral vein. [ABSTRACT FROM AUTHOR]

Study Design: A prospective cohort study.Objective: To demonstrate the changes in vitamin D status after surgery in female patients with lumbar spinal stenosis (LSS), and its correlation with surgical outcomes.Summary Of Background Data: In patients with LSS, general health including walking ability and nutritional status can be markedly improved by decompressive surgery. It can be hypothesized that such improvement may have a positive effect on their vitamin D status.Methods: In total, 31 female patients who underwent decompression and instrumented posterolateral fusion for LSS were enrolled. Serum 25-hydroxyvitamin D (25-OHD) level was measured before the surgery and at 1 year postoperative visit. According to serum 25-OHD level, patients were classified into 3 groups: (1) deficient group, when 25-OHD level was less than 20 ng/mL (< 50 nmol/L); (2) insufficient group, when 25-OHD level was between 20 to 30 ng/mL (50 nmol/L ≤ 25-OHD < 75 nmol/L); (3) and normal group, when 25-OHD level was 30 ng/mL or more (≥ 75 nmol/L). The Oswestry Disability Index (ODI) score and health-related quality of life (EQ-5D) were compared according to the level of 25-OHD at 1 year postoperatively.Results: Preoperatively, there were 20 patients in the deficient group, 11 patients in the insufficient group and no patient in the normal group. There were no differences in age, body mass index, preoperative ODI scores, preoperative EQ-5D index scores, and EQ-5D visual analogue scale scores between the 2 groups. Mean preoperative 25-OHD level was 15.8 ng/mL (range, 5.2-29.4 ng/mL) and increased to 19.5 ng/mL (range, 6.3-47.7 ng/mL) 1 year after surgery (P = 0.075). Significant increase of 25-OHD was noted only in the deficient group (P = 0.017). Postoperatively, there were 18 patients in the deficient group, 8 patients in the insufficient group, and 5 patients in the normal group. In the postoperative deficient group, postoperative ODI scores and EQ-5D index scores showed significantly worse outcomes than those in the other groups. The changes in serum 25-OHD level were significantly correlated with the changes in ODI scores (r = -0.580; P = 0.001) and with the changes in EQ-5D index scores (r = 0.379; P = 0.035). In all the groups, postoperative ODI scores (r = -0.665; P < 0.001) and EQ-5D index scores (r = 0.601; P < 0.001) were significantly correlated with postoperative 25-OHD level.Conclusion: Vitamin D deficiency was common in patients with LSS. However, vitamin D status was improved after decompressive surgery, and postoperative 25-OHD level was significantly correlated with surgical outcomes. [ABSTRACT FROM AUTHOR]

Main Conclusion: The microbial terpene synthase-like of the moss Sanionia uncinata displays the convergent evolution of a rare plant metabolite amorpha-4,11-diene synthesis. Despite increasing demand for the exploration of biological resources, the diversity of natural compounds synthesized by organisms inhabiting various climates remains largely unexplored. This study focuses on the moss Sanionia uncinata, known as a predominant species within the polar climates of the Antarctic Peninsula, to systematically explore its metabolic profile both in-field and in controlled environments. We here report a diverse array of moss-derived terpene volatiles, including the identification of amorpha-4,11-diene, a rare sesquiterpene compound that is a precursor for antimalarial drugs. Phylogenetic reconstruction and functional validation in planta and in vitro identified a moss terpene synthase, S. uncinata microbial terpene synthase-like 2 (SuMTPSL2), which is associated with amorpha-4,11-diene production. We demonstrate that expressing SuMTPSL2 in various heterologous systems is sufficient to produce amorpha-4,11-diene. These results highlight the metabolic diversity in Antarctica, but also provide insights into the convergent evolution leading to the synthesis of a rare plant metabolite., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest., (© 2024. The Author(s).)

Extracellular vesicles (EVs) are promising therapeutic biomaterials capable of transferring their cargo molecules and external drugs to other cells in vivo and contain various biomarkers that can be used in liquid biopsies. The clinical application of EVs requires an efficient EV enrichment system for the large-scale production or high-throughput isolation of EVs from liquid samples, such as culture media, plant juices, and body fluids. However, current EV enrichment methods, such as ultrafiltration and ultracentrifugation, have limited applicability owing to their associated costs, inefficiency, scalability, and centrifugation time. Herein, we describe the development of a nanosieve based on a superabsorbent polymer for selective EV enrichment. The nanosieve absorbs small molecules while expelling large molecules, such as EVs, through the nanosized channels. We successfully concentrated EVs from clinical samples, such as serum and plasma, with superior cost and time efficiencies. The nanosieves did not interact with the EVs during enrichment, allowing the retention of their therapeutic functions. In addition, the nanosieve surface was specifically engineered to provide multifunctionality to effectively promote EV capture from bulk solutions. Overall, our nanosieve-based EV enrichment method is effective, time- and cost-saving, versatile, scalable, and modulable, and is an excellent option for EV production.

Background: Placement of interradicular orthodontic miniscrews poses a potential risk of root damage, including superficial root contact and root fracture. This case report describes the iatrogenic root-injured tooth movement of a 27-year-old male with skeletal Class III malocclusion as nonsurgical orthodontic treatment., Case Presentation: An orthodontic miniscrew between the mandibular right first and second molars perforated the distal root of the mandibular first molar. A root fracture was discovered 4 months after miniscrew placement. Owing to the potential risk of ankylosis related to surgical intervention, a direct orthodontic distalizing force was applied towards the fractured distal root segment without additional treatment, resulting in considerable movement of the fractured tooth with maintaining tooth vitality. However, gradual root resorption of a fractured tooth with a separate root segment was observed. The mandibular arch distalization of skeletal Class III malocclusion was successfully performed and retained for 3 years 8 months with stable occlusion., Conclusions: This case reveals a clinical remedy when root movement of a tooth with root fracture is indicated. The use of extra-alveolar miniscrews or miniplates can be considered for mandibular arch distalization to prevent potential root injuries caused by miniscrew placement., Clinical Trial Number: Not applicable., Competing Interests: Declarations Ethics approval and consent to participate The patient provided the written informed consent for clinical management and publication of this case report. Consent for publication The patient provided the written informed consent for the publication of this case report. All authors transfer all copyright ownership of the manuscript to BMC Oral Health in the event the work is published. The author warrants that the article is original, is not under consideration for publication by another journal and has not been previously published. All authors accept responsibility for releasing this material. Clinical trial number Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Recently, cough reflex hypersensitivity has been proposed as a common underlying feature of chronic cough in adults. However, symptoms and clinical characteristics of cough hypersensitivity have not been studied amongst phenotypes of chronic cough. This study aimed to compare symptom features, such as cough triggers and associated throat sensations, of cough hypersensitivity in patients with asthmatic chronic cough and those with refractory chronic cough (RCC)., Methods: Patients with chronic cough from the Korean Chronic Cough Registry were prospectively evaluated over 6 months. Physicians determined the aetiological diagnosis based on clinical evaluations and responses to treatment at the 6-month follow-up visit. Symptoms of cough hypersensitivity and cough-specific quality of life were assessed using the Cough Hypersensitivity Questionnaire (CHQ) and the Leicester Cough Questionnaire (LCQ), respectively., Results: The analysis included 280 patients who completed the follow-up: 79 with asthmatic cough (cough variant asthma or eosinophilic bronchitis) and 201 with RCC. Baseline CHQ scores were similar between the groups (8.3±3.7 in asthmatic cough versus 8.9±3.9 in RCC; p=0.215, adjusted for age, sex and LCQ score). There were no significant between-group differences in the LCQ and cough severity Visual Analog Scale scores. Both groups showed a similar negative correlation with LCQ scores (asthmatic cough: r=-0.427, p<0.001; RCC: r=-0.306, p<0.001)., Conclusions: The symptoms of cough hypersensitivity may not distinguish between asthmatic cough and RCC. This suggests that chronic cough is the primary diagnosis in both phenotypes. It indicates a shared mechanism in their cough pathogenesis, despite having potentially different treatable traits., Competing Interests: Conflict of interest: S.S. Birring declares grants from Merck Sharp & Dohme Corp. and consulting fees from Merck, Shionogi, Bayer, Nerre, Genentech/Roche and Bellus. Conflict of interest: W-J. Song declares grants from Merck Sharp & Dohme Corp. and AstraZeneca; consulting fees from Merck, Bellus, AstraZeneca, Shionogi and GSK; and lecture fees from Merck, AstraZeneca, GSK, Sanofi and Novartis; and is deputy chief editor of this journal. Conflict of interest: The other authors declare that they have no competing interests., (Copyright ©The authors 2024.)

This study aimed to investigate the association between gait profile and spinal alignment in adolescent idiopathic scoliosis (AIS). The study group consisted of 80 AIS and 80 healthy controls. All participants underwent radiographic imaging and measured gait analysis. The gait profile included gait speed, step length, stance phase, cadence, single leg support, double legs support, gait asymmetry (GA), and phase coordination index (PCI). The spinal alignment parameters included pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), and coronal balance (CB). The mean age of the AIS group was 15.1 years, while the control group was 14.6 years. Significant differences were observed between the AIS patients and controls in gait speed, step length, stance phase, cadence, single leg support, double legs support, GA, PT, TK, SVA, and CB. However, no significant differences were found in PCI, SS, PI, and LL (p > 0.05). Additionally, correlation analysis revealed a close relationship between gait profile and spinal alignment parameters. Step length was significantly related to PT, SS, and LL, while GA was correlated with TK in AIS patients. Multiple regression analysis for predictors of step length found that PT and SS accurately predicted step length. First, the AIS group showed significant differences in gait kinematics and spinal alignment compared to the control group. Second, statistically significant correlations were found between gait profile and spinal alignment parameters. Specifically, PT and SS accurately predicted step length, and TK was correlated with GA in AIS patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: This study aimed to compare the outcomes and complications of active young adults undergoing open reduction and plate fixation (ORPF) and intramedullary nailing (IMN) for displaced midshaft clavicle fractures (MCFs)., Methods: A retrospective review was performed on all patients undergoing ORPF and IMN of complete MCFs at a single center between 2018 and 2022. Patients who were younger than 60 years with radiographic follow-up until union were included in the study. The mean age of the patients was 33.1 years. Outcome measures were achievement of union, time to healing, residual deformity, complications, and need for additional procedures., Results: Of 39 patients, 29 underwent ORPF and 10 underwent IMN. Plate fixation provided faster functional recovery in the first 6 months, but no difference was observed after 1 year. All fractures in the IMN group healed (100%), compared to 90% in the ORPF group (P=0.08). Mean time to union was 21±8.9 weeks and was significantly different between the two groups (P<0.01), with the ORPF group averaging 23.1 weeks and the IMN group 20.8 weeks. Nonunion rates were higher in the ORPF group (10.3%) than in the IMN group (0.0%), but the difference was not significant (P=0.10)., Conclusions: Both methods restored patients to their pre-injury functional levels. However, IMN, with its higher healing rate, fewer required revision surgeries, and lower incisional numbness, appears to be the preferred method for treating MSFs without comminution in young adults. Level of evidence: III.

Background: Phragmites australis is a common foundation species found in inland and brackish estuarine ecosystems. P. australis stands provide a wide range of habitats for wetland organisms and perform essential functions, such as nutrient cycling, pollutant filtration, wave energy reduction, and soil stabilization. However, excessive growth of P. australis can degrade the quality of wetland habitats, thereby reducing the functions of restored wetlands., Methods: In this study, we investigated the effectiveness of vegetation management techniques, such as aboveground cutting and temporal inundation with varying depth and periodicity, in controlling the growth performance of P. australis and adjacent vegetation, Bolboschoenus planiculmis . Differences in growth responses to manipulated inundation stress between P. australis and B. planiculmis were measured., Results: Inundation stress of 10-50 cm caused significantly greater inhibition of growth performance in B. planiculmis compared to P. australis . The combination of aboveground-cutting and inundation treatments resulted in a significant inhibitory effect on the growth performance and survival rate of P. australis . The growth performance of P. australis , including stem volume and biomass, decreased and its mortality rate increased. Our manipulated experiment suggests a combined treatment approach of moderate inundation, such as 5-10 cm for 20-30 days, and aboveground cutting to manage the overgrowth of P. australis in restored brackish wetlands., Competing Interests: The authors declare that they have no competing interests., (© 2024 Park et al.)

Population genomics has great potential to inform applied conservation management and associated policy. However, the bioinformatic analyses and interpretation of population genomic datasets can be daunting and difficult to convey to nonspecialists, including on-the-ground conservationists that work with many state, federal and international agencies. We think that individual population genomic metrics of interest can be interpolated and ultimately distilled into thematic GIS layers that represent spatiotemporal genomic potential (or conversely, susceptibility) in conservation monitoring. As examples relevant to ongoing conservation efforts, we use introgressive hybridisation and individual heterozygosity to illustrate a conceptual approach for mapping population genomic susceptibility. The general framework of thematic layers could be extended to integrate key genomic metrics (e.g., runs of homozygosity and genomic load) that are relevant to many conservation efforts., (© 2024 The Author(s). Molecular Ecology published by John Wiley & Sons Ltd.)

Metabolic syndrome is a significant risk factor for poor graft outcomes in kidney transplant (KT) patients. However, the effects of variability in metabolic parameters on graft outcomes in KT patients have not been completely elucidated. A total of 852 KT patients were included from the Korean Organ Transplantation Registry. The study exposure was variability in body mass index (BMI) or other metabolic parameters measured at 6 months, 1 year, and 2 years after KT. Patients were classified into tertiles according to the degree of variability. The primary outcome was a composite of adverse kidney outcomes, such as death-censored graft loss or ≥ 30% decline in estimated glomerular filtration rate. The adverse kidney outcomes occurred in 73 (8.6%) participants. The high-BMI variability group had a higher risk for adverse kidney outcomes compared to the low-variability group. High variabilities in triglyceride, fasting blood glucose, and systolic blood pressure were also associated with adverse kidney outcomes. Furthermore, high variability in metabolic syndrome-related composite indices, such as the triglyceride and glucose index and metabolic variability scores, showed a higher risk for adverse kidney outcomes. In conclusion, high variability in metabolic parameters could be associated with an increased risk of adverse kidney outcome in KT patients., (© 2024. The Author(s).)

Background and Study Aims: We aimed to evaluate the association between colonoscopy (CS) and colorectal cancer (CRC) occurrence and related mortality in an older population., Patients and Methods: This retrospective, nationwide, population-based cohort study used data of adults aged ≥40 years from the Health Insurance Review and Assessment Service database. After excluding CS within 6 months of CRC diagnosis during enrollment, CRC occurrence and related mortality were compared between CS and non-CS groups using a time-dependent Cox proportional hazard model. Sub-group analysis was conducted among four age groups: young, middle age, old, and very old. Results Among 748,989 individuals followed for 9.64±0.99 years, the CS group had a 65% lower CRC occurrence (adjusted hazard ratio [HRa]: 0.35, 95% confidence interval [95%CI]: 0.32-0.38) and 76% lower CRC-related mortality (HRa: 0.24, 95%CI: 0.18-0.31) after 5 years than the non-CS group. CS was associated with the most significant reduction in CRC occurrence in the middle age group (HRa: 0.32, 95%CI: 0.29-0.35) and CRC-related mortality in the young age group (HRa: 0.04, 95%CI: 0.01-0.33); the very old age group had the least reduction in both CRC occurrence and CRC-related mortality (HRa: 0.44, 95%CI: 0.33-0.59 and HRa: 0.28, 95%CI: 0.15-0.53, respectively). Conclusion We found a significant association between colonoscopy and reduction in CRC occurrence and CRC-related mortality in adults aged ≥ 40 years after 5 years of follow-up; however, these associations were weaker in the very old group. Research is needed on the association between colonoscopy and older age., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Importance: Previous studies have indicated an inverse association between income and mortality. However, differences in health outcomes according to the income level of young adults with type 2 diabetes (T2D) compared with older adults with T2D have not been elucidated., Objective: To estimate the overall and cause-specific mortality risks among patients with T2D according to income and age., Design, Setting, and Participants: This retrospective nationwide cohort study in South Korea included adults aged 20 to 79 years who were diagnosed with T2D between January 1, 2008, and December 31, 2013, and followed up until December 31, 2019, and age- and sex-matched controls without diabetes. Data were analyzed between January 1, 2023, and August 27, 2024., Main Outcomes and Measures: Risks of all-cause, cardiovascular, and cancer mortality were estimated according to participants' income, which was categorized into 3 levels (low, middle, and high) based on the health insurance premium. Logistic regression analyses and Cox proportional hazard regression analyses were performed according to age groups (20-39, 40-59, and 60-79 years)., Results: A total of 1 240 780 adults (604 975 patients with T2D and 635 805 age- and sex-matched controls without diabetes) were included in the analyses. Their mean (SD) age was 56.9 (11.8) years, and 626 176 (50.5%) were men. Overall, the risk of mortality increased with lower income among patients with T2D, as well as in comparison with controls without diabetes. There was an inverse association between income and mortality risk in younger individuals (adjusted hazard ratios of all-cause mortality in the low income vs high income subgroups with T2D were 2.88 [95% CI, 2.25-3.69] in those aged 20 to 39 years, 1.90 [95% CI, 1.81-2.00] in those aged 40 to 59 years, and 1.26 [95% CI, 1.23-1.29] in those aged 60 to 79 years; P < .001 for comparing risk ratios between age groups). The pattern of income-related disparities in younger individuals was observed in cardiovascular mortality but less in cancer mortality., Conclusions and Relevance: In this cohort study of 1 240 780 individuals aged 20 to 79 years, the risk of mortality with low income was most prominent among individuals with T2D aged 20 to 39 years. These findings highlight the need for socioeconomic support to reduce income-related health disparities in younger individuals.

Background and Aims: The association between metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) is unclear. This study aimed to investigate the impact of spectrum of SLD on the risk of heart failure and cardiovascular (CV) mortality in patients with T2DM., Methods: In a nationwide cohort study, 2,745,689 adults with T2DM were followed from 2009 to 2012 until 2018. Participants were categorized into no steatotic liver disease (no SLD) and SLD groups. The SLD group was stratified based on metabolic risk factors, alcohol consumption and viral hepatitis. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for heart failure (HF) and CV mortality risk., Results: The prevalence of MASLD, metabolic alcohol-associated liver disease (MetALD), alcohol-associated liver disease with metabolic dysfunction (ALD with MD) and MASLD with viral hepatitis (VH) was 49.6%, 7.2%, 2.3%, and 2.0%. Individuals with MASLD (adjusted HR [aHR], 1.11), MetALD (aHR, 1.14), ALD with MD (aHR, 1.32) and MASLD with VH (aHR, 1.12) had a higher risk of developing HF compared with the no SLD group. The risk of CV mortality was also increased in those with SLD groups compared to those with no SLD. The risk of new-onset HF and CV mortality showed a J-shaped association with alcohol consumption regardless of SLD status., Conclusion: SLD is independent risk factor of new-onset HF and CV mortality in persons with T2DM, and alcohol consumption has a J-shaped association with risk of HF and CV mortality, regardless of SLD status., (© 2024. The Author(s).)

Haplotype-level allelic characterization facilitates research on the functional, evolutionary and breeding-related features of extremely large and complex plant genomes. We report a 21.7-Gb chromosome-level haplotype-resolved assembly in Pinus densiflora. We found genome rearrangements involving translocations and inversions between chromosomes 1 and 3 of Pinus species and a proliferation of specific long terminal repeat (LTR) retrotransposons (LTR-RTs) in P. densiflora. Evolutionary analyses illustrated that tandem and LTR-RT-mediated duplications led to an increment of transcription factor (TF) genes in P. densiflora. The haplotype sequence comparison showed allelic imbalances, including presence-absence variations of genes (PAV genes) and their functional contributions to flowering and abiotic stress-related traits in P. densiflora. Allele-aware resequencing analysis revealed PAV gene diversity across P. densiflora accessions. Our study provides insights into key mechanisms underlying the evolution of genome structure, LTR-RTs and TFs within the Pinus lineage as well as allelic imbalances and diversity across P. densiflora., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Multiplex immunofluorescence (mIF) staining plays an important role in profiling biomarkers and allows investigation of co-relationships between multiple biomarkers in the same tissue section. The Cell DIVE mIF platform (Leica Microsystems) employs an alkaline solution of hydrogen peroxide as a fluorophore inactivation reagent in the sequential staining, imaging, and bleaching protocol for use on FFPE sections. Suboptimal bleaching efficiency, degradation of tissue structure, and loss of antigen immunogenicity occasionally are encountered with the standard bleaching process. To overcome these impediments, we adopted a modified photochemical bleaching method, which utilizes an intense LED light exposure concurrent with the application of hydrogen peroxide. Repeated stain/bleach rounds with different antibodies were performed on breast tissue and other tissue sections. Residual signal after conventional bleaching and the modified technique were compared and tissue integrity and antigen immunogenicity were assessed. The modified technique effectively eliminates fluorescence signal from previous staining rounds and produces consistent results for multiple rounds of staining and imaging. With the modified method, photochemical treatments did not destroy tissue sub-cellular contents, and the tissue antigenicity was well preserved during the entire mIF process. Overall processing time was reduced from 36 to 30 hours in an mIF procedure with 8 rounds. With the conventional method, tissue quality was highly degraded after 8 rounds. The new technique allows reduced turn-around time, provides reliable fluorophore removal in mIF with excellent maintenance of tissue integrity, facilitating studies of the co-localization of multiple biomarkers in tissues of interest., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Erastin, a ferroptosis-inducing system x c - inhibitor, faces clinical challenges due to suboptimal physicochemical and pharmacokinetic properties, as well as relatively low potency and off-target toxicity. Addressing these, we developed ECINs, a novel laser-responsive erastin-loaded nanomedicine utilizing indocyanine green (ICG)-grafted chondroitin sulfate A (CSA) derivatives. Our aim was to improve erastin's tumor targeting via CSA-CD44 interactions and enhance its antitumor efficacy through ICG's photothermal and photodynamic effects in the laser-on state while minimizing off-target effects in the laser-off state. ECINs, with their nanoscale size of 186.7 ± 1.1 nm and high erastin encapsulation efficiency of 93.0 ± 0.8%, showed excellent colloidal stability and sustained drug release up to 120 h. In vitro, ECINs demonstrated a mechanism of cancer cell inhibition via G1-phase cell cycle arrest, indicating a non-ferroptotic action. In vivo biodistribution studies in SK-HEP-1 xenograft mice revealed that ECINs significantly enhanced tumor distribution of erastin (1.9-fold greater than free erastin) while substantially reducing off-target accumulation in the lungs and spleen by 203-fold and 19.1-fold, respectively. Combined with laser irradiation, ECINs significantly decreased tumor size (2.6-fold, compared to free erastin; 2.4-fold, compared to ECINs without laser irradiation) with minimal systemic toxicity. This study highlights ECINs as a dual-modality approach for liver cancer treatment, demonstrating significant efficacy against tumors overexpressing CD44 and system x c - ., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Oropharyngeal dysphagia (dysphagia) is highly prevalent (up to 86%) in hospitalized patients with Alzheimer disease and related dementias (ADRD). This study aims to describe the management and clinical course of dysphagia in hospitalized patients with ADRD., Design: Prospective observational cohort study., Setting and Participants: The study was conducted across 10 hospitals within a large health system in New York. Participants were older adults with ADRD admitted to the medicine service and diagnosed with dysphagia to liquids on speech-language pathologist (SLP) assessment and were recruited between January and June 2023., Methods: Baseline characteristics [eg, dementia Functional Assessment Staging Tool (FAST)], dysphagia management (eg, prescribed diet), and clinical course (eg, dysphagia improvement, respiratory complications) were collected., Results: Of patients with ADRD and dysphagia (n = 62), the average age was 86.5 and 66.1% were FAST Stage 7. On admission, 48.4% had pneumonia, 79.0% had delirium, and 69.4% were made nil per os (NPO) for aspiration risk. Of those who received SLP reassessment after diet initiation (n = 25), 76% demonstrated dysphagia improvement; 75% of patients with FAST stage 7 demonstrated improvement. Respiratory complications occurred in 21.0% of patients on the following diets: NPO, nasogastric tube feeding, dysphagia diets, and comfort feeds. In univariate analyses, hospital-acquired dehydration, no dysphagia improvement, and delirium were associated with respiratory complications., Conclusions and Implications: The potential for dysphagia improvement in hospitalized patients with ADRD (even those with advanced dementia) highlights the critical need for standardizing reassessment. Further studies are needed to evaluate factors associated with respiratory complications in this population., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Objective: Spinal intramedullary hemangioblastoma is a rare and highly vascularized benign tumor. The characteristics of the tumor, its corresponding location, and surgical outcomes remain unknown. The purpose of this study was to identify risk factors and strategies for neurologic deterioration following hemangioblastoma surgery., Methods: A comprehensive retrospective analysis was undertaken to evaluate patients who underwent surgical intervention for intramedullary hemangioblastoma at our institution from 1993 to 2022. Patients with at least 1 year of follow-up data were included. The analysis covered patient demographics, pre- and post-operative modified McCormick scale (MMCS), tumor location, and tumor size., Results: This study included 25 cases. One-year after surgery, neurological deterioration was observed in five cases (20.0%), and neurological improvement was found in nine cases (36.0%). Five cases were ventrally located, and twelve cases were dorsally located. Ventrally located cases were larger in tumor axial size (p=0.029) than dorsal location tumors, resulting in poorer follow-up MMCS and a higher prevalence of von Hippel-Lindau syndrome (VHL) (p=0.042). Three of them were confirmed to be supplied by the anterior spinal artery. In the case of dorsally located cases, there was no neurologic deterioration., Conclusion: In intramedullary spinal cord hemangioblastomas, cases located ventrally had a higher incidence of neurological deterioration following surgery than those located dorsally or in intramedullary extramedullary cases. Ventrally located hemangioblastomas were larger than those in other locations. They were mainly supplied by the anterior spinal artery in VHL patients.

This study examined negative life changes due to coronavirus disease of 2019 (COVID-19) and its correlates in a sample of community-dwelling older adults from a low-income urban city in Korea, focusing on gendered differences. Negative life changes due to COVID-19 were categorized into four domains: behavioral/physical, psychosocial, goal-seeking, and control/freedom. Being female, not receiving basic livelihood security, and dissatisfaction with housing situation were significantly associated with negative life changes during the pandemic. Gender-stratified analyses revealed that most within-gender social disparities associated with changes due to COVID-19 occurred in older women. The odds of experiencing negative changes were higher among working women and those receiving security income aid. In low-income urban communities, those who were previously socially and economically active perceived more negative changes owing to the pandemic. The contribution of gender to negative life changes should be considered to effectively alleviate concerns among older adults during pandemics., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Extracranial vascular malformations affect vessel inflammation, clotting, and ischemia. However, the relationship between extracranial vascular malformations and myocardial infarction (MI) or stroke has not been fully elucidated. Limited studies have investigated the association between extracranial vascular malformations and cardiovascular diseases., Methods: A total of 48,701 patients with extracranial vascular malformations and a control cohort of 487,010 age- and sex-matched participants from the Korean National Health Insurance database were included. The incidence and risk of MI, ischemic stroke (IS), and hemorrhagic stroke (HS) between participants with extracranial vascular malformations and the control cohort was compared., Results: After adjusting for other cardiovascular disease risk factors, the adjusted hazard ratios (aHRs) for venous malformations, capillary malformations (CMs), arteriovenous malformations (AVMs), and lymphatic malformations in patients with acute MI were 1.25 (CI, 1.04 to 1.50), 1.41 (CI, 1.24 to 1.61), 1.68 (CI, 1.18 to 2.37), and 1.40 (CI, 1.31 to 1.48), respectively. For IS, the aHRs were 1.55 (CI, 1.35 to 1.77), 1.92 (CI, 1.74 to 2.11), 1.13 (CI, 0.78 to 1.64), and 1.51 (CI, 1.44 to 1.58), respectively. For HS, the aHRs were 1.51 (CI, 1.12 to 2.05), 5.63 (CI, 4.97 to 6.38), 2.93 (CI, 1.82 to 4.72), and 1.34 (CI, 1.20 to 1.50), respectively., Conclusions: Independent of cardiovascular risk factors, extracranial vascular malformations were associated with an increased risk of MI, IS, and HS. For patients with CMs and AVMs, intracerebral hemorrhage risk was particularly high, accounting for 563% and 293%, respectively. Therefore, even in patients with extracranial CMs or AVMs, performing diagnostic evaluations for cerebral AVMs and using measures to prevent intracerebral hemorrhage are crucial., Clinical Question/level of Evidence: Risk, II., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)

Background: Accurate identification of eosinophilic chronic rhinosinusitis is essentialg because its treatment and prognosis substantially differ from other subtypes., Methods: This retrospective observational study included 640 patients who underwent endoscopic sinus surgery for chronic rhinosinusitis in a single tertiary center from January 2021 to December 2022. Receiver operating characteristic curves were generated to compare accuracy, sensitivity, specificity of the novel scoring system, and previous diagnostic criteria (Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis, European Forum for Research and Education in Allergy and Airway Diseases, European Position Paper on Rhinosinusitis and Nasal Polyps, and Sakuma et al.) for predicting eosinophilic chronic rhinosinusitis (ECRS) by tissue eosinophil count ≥70 per high power field., Results: Patients were randomly divided into estimation (n = 430) and validation (n = 210) groups. The area under the receiver operating characteristic curve for the novel score was 0.753 (95% confidence interval [CI], 0.670-0.835) in the estimation group, 0.729 (0.629-0.830) in the validation group, and 0.661 (0.584-0.738) in the 20-fold cross-validation with the entire dataset., Conclusions: We propose a novel scoring system that incorporates three key parameters: "novel score = blood eosinophil (%) + total Lund-Mackay score of anterior ethmoid sinuses + 2 if nasal polyp present" greater than 7 can be reliably used for diagnosing ECRS. This system can facilitate decision-making processes regarding the administration of oral steroids and biologics targeting type 2 inflammation prior to surgical intervention., (© 2024 ARS‐AAOA, LLC.)

Objective: Neutrophils produce neutrophil extracellular traps (NETs) by releasing nuclear contents into the extracellular environment. NETs are associated with systemic inflammation and cancer development and progression. We aimed to investigate whether NET markers are associated with the prognosis of endometrial cancer., Methods: Circulating levels of three NET markers (histone-DNA complex, cell-free double-stranded DNA (dsDNA), and neutrophil elastase) were measured in 98 patients with endometrial cancer who underwent surgery as primary treatment between January 2015 and June 2018 and 45 healthy women. Area under the receiver operating characteristic curve (AUC) analyses were conducted to investigate the diagnostic and prognostic utility of the markers for endometrial cancer., Results: Patients with endometrial cancer showed significantly higher levels of the three NET markers than those in healthy controls. In discriminating endometrial cancer patients from healthy controls, the three NET markers showed AUC values in the following order: cell-free dsDNA (0.832; 95 % CI, 0.760-0.889), histone-DNA complex (0.740; 95 % CI, 0.660-0.809), and neutrophil elastase (0.689; 95 % CI, 0.607-0.764), comparable to those of CA-125 (0.741; 95 % CI, 0.659-0.813). Multivariate analysis adjusting for FIGO stage, histology, and lymphovascular space invasion, and lymph node involvement revealed that cell-free dsDNA level (cutoff: 95.2 ng/mL) was an independent prognostic marker for poor progression-free (adjusted HR, 2.75; 95 % CI, 1.096.92; P = 0.032) and overall survival (adjusted HR, 11.51; 95 % CI, 2.0664.22; P = 0.005) for patients with endometrial cancer., Conclusion: High levels of circulating NET markers were observed in patients with endometrial cancer. Cell-free dsDNA levels may play a role as prognostic markers for endometrial cancer., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

The East Asian finless porpoise, Neophocaena asiaeorientalis sunameri, is an endangered species that inhabits the coastal marine environments of East Asia. In the present study, we investigated the overall infection status of anisakid nematodes in East Asian finless porpoises from three sea sectors off the Korean Peninsula. The genetic diversity and population genetic structure of the identified nematode species were evaluated. The prevalence of all stages of anisakid nematodes collected from the stomach was 57.55% (61 among the 106 porpoises examined), and 16 of the hosts were found to have adult worms. The mean number of infected adults was 211 (± 419.54, 5-1455 per host). Only one species of anisakids, Anisakis pegreffii, was identified from randomly selected worms by molecular approaches. Analysis of the mitochondrial (mt) cox2 partial gene in 50 newly generated sequences of A. pegreffii revealed 24 haplotypes, including 14 new haplotypes. We observed below-average levels of nucleotide diversity and haplotype diversity compared to other seas around the world. The mtDNA cox2 haplotypes of the species in the three Korean sea areas showed no genetic structure, suggesting well-connected gene flow within these areas. This study represents the first record of a definitive host of A. pegreffii in Korean waters, providing important information regarding anisakids genetic diversity in the cetacean species inhabiting limited regions., (© 2024. The Author(s).)

The development of catalysts that are optically transparent, electrically charge-transferable, and capable of protecting underlying photoactive semiconductors is crucial for efficient photoelectrochemical (PEC) hydrogen production. However, meeting all these requirements simultaneously poses significant challenges. In this study, the fabrication of a wafer-scale transparent bilayer MoS 2 /WS 2 catalyst is presented with a staggered heterojunction, optimized for photon absorption, extraction of photogenerated charge carriers, and surface passivation of p-Si photocathode. The MoS 2 and WS 2 monolayers are grown via metal-organic chemical vapor deposition, followed by sequential transfer and stacking onto the p-Si photocathode. The resulting type-II heterojunction film establishes a strong built-in electric field for rapid charge carrier transport and effectively protects the Si surface from oxidation and corrosion. The fabricated MoS 2 /WS 2 /p-Si photocathode demonstrates outstanding PEC performance, achieving a high photocurrent density of -25 mA cm -2 at 0 V versus reversible hydrogen electrode, along with enhanced stability compared to monolayer MoS 2 /p-Si. This work provides promising strategies for developing optically transparent, electrically active, and protective catalysts for practical PEC energy conversion systems., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Background/aims: The use of 1-L polyethylene glycol with ascorbate (PEG/Asc) and oral sulfate tablets (OST) as low-volume bowel preparation agents has gradually increased. However, these agents may induce acute gastropathy during bowel preparation, particularly in elderly populations. This study aimed to compare the incidence of acute gastropathy of 1-L PEG/Asc and OST according to age, as well as efficacy and safety., Methods: This retrospective study included patients who underwent esophagogastroduodenoscopy (EGD) and colonoscopy for screening on the same day and underwent bowel preparation using OST or 1-L PEG/Asc. We collected EGD findings related to acute gastropathy, bowel-cleansing score using the Boston Bowel Preparation Scale (BBPS), polyp or adenoma detection rate (ADR), and laboratory parameters., Results: Of 4,711 patients, 1,758, 2,241, and 712 were in the younger (18-49 years), middle-aged (50-64 years), and older (≥65 years) groups, respectively. In all age groups, the OST group had higher rates of acute gastropathy than the 1-L PEG/Asc group. The younger-, middle-, and older-aged groups had OST and 1-L PEG/Asc usage rates of 42.9% and 11.6%, 41.2% and 16.0%, and 41.5% and 16.4%, respectively. Notably, in the younger group, the total BBPS and ADR scores were significantly higher in the OST group than in the 1-L PEG/Asc group; however, these did not differ in the other age groups., Conclusions: Acute gastropathy was more strongly associated with OST than with 1-L PEG/Asc in all age groups. Therefore, physicians should consider acute gastropathy associated with low-volume agents in all age groups when performing bowel preparation.

Aims: To identify the components and characteristics of disaster risk reduction education for people with disabilities and to explore the contents and results of disaster risk reduction education., Design: A systematic review and narrative synthesis., Review Methods: The review was conducted in accordance with Tawfik's guidelines and followed the reporting standards outlined in the Preferred Reporting Items for Systematic reviews and Meta-Analysis. The quality appraisal was guided by the mixed methods appraisal tool. The contents of each type of education were narratively synthesised., Data Sources: The literature search was conducted in December 2023 using several electronic databases, including PubMed, EMBASE, CINAHL, Cochrane library and PsycINFO., Results: Eight quantitative studies were selected for this study. Disaster risk reduction education for people with disabilities has focused mainly on fires and earthquakes, and drills were the most used teaching method. Some of the education was conducted by designating a 1:1 ratio of educators and participants or modifying the ratio according to the type of disability. The staff mainly conducted the education, and after education, the effect of disaster risk reduction education was confirmed in terms of the knowledge and response of people with disabilities during drills., Conclusion: This review provides insights for developing disaster risk reduction education for people with disabilities. However, only a few randomised controlled trial (RCT) studies and quasi-experimental studies have been conducted, and several studies have bias risks. Thus, practical, continuous, quality interventions are needed for effective disaster risk reduction education for people with disabilities., Impact: This systematic review analysed the research trends of disaster risk reduction education for people with disabilities. The results provide the basis for quality evaluations of the operation, methods and achievements of educational programmes. Efforts are needed to promote collaboration between researcher and the practitioners to conduct further quality research., Patient or Public Contribution: No Patient or Public Contribution: Systematic review., (© 2024 John Wiley & Sons Ltd.)