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We investigated plasma phosphorylated tau217 (p-tau217) and p-tau181 efficacy in predicting positive amyloid positron emission tomography (PET) results and cognitive stage transitions. Plasma p-tau217 and p-tau181 were measured in participants who were cognitively unimpaired (CU, n = 121), had mild cognitive impairment (n = 102), or dementia (n = 75) from two independent cohorts (Cohort 1: KBASE-V and Cohort 2: Asan) who underwent amyloid PET. In Cohort 1, plasma p-tau217 (area under the curve [AUC] = 0.938, P < 0.001) outperformed p-tau181 (AUC = 0.857, P < 0.001) in predicting amyloid PET positivity (P difference  < 0.001). In Cohort 2, p-tau217 (AUC = 0.893, P < 0.001) and p-tau181 (AUC = 0.856, P < 0.001) showed comparably good discrimination for predicting amyloid PET positivity (P = 0.377). P-tau217 (AUC = 0.852, P < 0.001) and p-tau181 (AUC = 0.828, P < 0.001) demonstrated similarly good discriminations for predicting cognitive stage transition (P difference  = 0.093). Plasma p-tau217 and p-tau181 predicted amyloid PET positivity and cognitive stage transitions well. Plasma p-tau217 might perform better, especially in the early stages., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Consent for publication: Not applicable. Consent statement: This study was performed in accordance with the Good Clinical Practice guidelines and the Declaration of Helsinki and was approved by the Institutional Review Boards of the Asan Medical Center (Approval #2018-0614), Inha University Hospital (INHAUH 2015-03-021), and each participating center. All participants or their proxies provided written informed consent., (© 2025. The Author(s).)

Background: Cytomegalovirus (CMV) infection is a frequent complication after kidney transplantation (KT) and has various effects on recipient and graft survival. Although guidelines recommend anti-viral prophylaxis with ganciclovir or valganciclovir, there is a demand for alternative regimen for CMV prevention. We investigated the effects of a 3-month valacyclovir-based prophylaxis on CMV infection and clinical outcomes in KT recipients using a nationwide cohort., Methods: Overall, 2,584 KT recipients from 20 transplant centers registered with the Korean Organ Transplantation Registry between May 2014 and December 2019 were analyzed in this study. The recipients were divided into valacyclovir prophylaxis and non-prophylaxis groups, a 1:3 propensity score matching was performed, and 1,036 recipients (291 and 745 in the prophylaxis and non-prophylaxis groups, respectively) were analyzed. The impact of valacyclovir-based prophylaxis on CMV after KT, other clinical outcomes, and the risk factors for CMV infection development were investigated., Results: The prophylaxis group showed a lower incidence of CMV infection and rejection compared to the non-prophylaxis group (3.64 vs. 10.25 events/100 person-years and 1.85 vs. 7.27 events/100 person-years, respectively). Valacyclovir prophylaxis, donor age, deceased donor, length of hospitalization after KT, anti-thymocyte globulin use, and CMV serological mismatch between the donor and recipient were independent risk factors for CMV infection after KT., Conclusions: Valacyclovir prophylaxis after KT significantly reduced CMV infection and rejection. We suggest that valacyclovir could be considered as an alternative strategy for CMV prophylaxis after KT. However, our study has limitations, including its retrospective design, variability in valacyclovir dosing and CMV monitoring, and unassessed confounding factors. Further prospective studies with standardized protocols and larger cohorts are needed to validate our findings., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was reviewed and approved by the Institutional Review Board of each center and the National Evidence-based Healthcare Collaborating Agency (NECA-IRB number: NECAIRB21-002). The need for informed consent was waived by the Institutional Review Board of each center (Kyung Hee University Hospital, Kyung Hee University Hospital at Gangdong, Seoul St. Mary's Hospital, Korea University Anam Hospital, Kyungpook National University Hospital, Keimyung University Dongsan Hospital, Pusan National University Hospital, Seoul National University Bundang Hospital, Seoul National University Hospital, Severance Hospital, CHA Bundang Medical Center, Samsung Medical Center, Soonchunhyang University Seoul Hospital, Inje University Busan Paik Hospital, Chonnam National University Hospital, Kangdong Sacred Heart Hospital, Incheon St. Mary's Hospital, Wonju Severance Christian Hospital, Kosin University Gospel Hospital, Eunpyeong St. Mary's Hospital) and the National Evidence-based Healthcare Collaborating Agency. Consent for publication: Not application. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Livestock, particularly cattle, are crucial for biotechnology fields, such as genetic breeding, infectious diseases, bioreactors, and specific disease models. However, genetic engineering in cattle has lagged due to long gestation periods, single embryo pregnancies, and high rearing costs. Additionally, the slow validation of germline transmission and the absence of germline-competent embryonic stem cells hinder progress. With the development of genome editing technologies like ZFN, TALEN, and CRISPR-Cas9, recent advancements have shown that Cas9-expressing pigs and chickens have been successfully produced. We hypothesize that generating CRISPR/Cas9-expressing cattle and their resources will provide a powerful resource for bovine genome editing, advancing our understanding of bovine genetics and disease resistance., Results: In this study, two types of Cas9-expressing cattle were successfully produced: Cas9-RFP-fatty acid dehydrogenase I (FatI), Cas9-GFP-sgRNA for the prion protein (sgPRNP). Somatic cells from these cattle were induced to mutate multiple target genes when single-guide RNAs (sgRNAs) were transfected into the somatic cells. Additionally, semen from Cas9 expressing male cattle was frozen and used to fertilize wild-type oocytes, successfully transmitting the transgene (Cas9, reporter genes, FatI), and sgPRNP) to the next generation. Furthermore, the gene editing capabilities of Cas9, including knockout and high-efficiency knock-in, were confirmed in embryos derived from F1 semen through in vitro production., Conclusion: These data demonstrate, for the first time, that Cas9-expressing cattle were successfully born, and this transgene was transmitted to the next-generation calves (F1) and F2 embryos. In addition, somatic and germ cells derived from F0 and F1generations were used to evaluate the potential for gene editing (knockout and knock-in) in multiple genes. PRNP-mutated F1 cattle are currently being raised as a resistance model for bovine spongiform encephalopathy. These transgenic bovine models and their derivatives will serve as a valuable resource for both in vitro and in vivo genome editing, advancing our genetic understanding of bovine genomics and diseases., Competing Interests: Declarations. Ethics approval and consent to participate: This study was carried out in accordance with the guidelines for Institutional Animal Care and Use Committee of Seoul National University (IACUC # SNU-180403–1-2). Additionally, approval for the animal experiments was obtained from the Institutional Animal Care and Use Committee (IACUC #106) of the Gyeongsangbuk-do Livestock Research Institute, and all relevant national laws and policies regarding animal care and use were followed throughout. All procedures, including embryo transfer for animal production, animal care and rearing, genotyping through tissue sampling, blood collection, and sperm collection, were conducted with approval from the IACUC #106. The heifers were housed in a stanchion barn with adequate space and were fed according to the Korean feeding standard program. Rice straw, mineral blocks, and water were provided without restriction. All animal procedures, including blood collection and embryo transfer, were performed by a veterinarian. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: Although HER2 positivity is prevalent in microinvasive breast cancer (MIBC), data focused on HER2-positive MIBC are limited. We investigated the clinical course and long-term outcomes of HER2-positive MIBC and evaluated the role of adjuvant chemotherapy., Materials and Methods: The study included patients with curatively resected pT1mi pN0 HER2-positive breast cancer between January 2000 and January 2020. Treatments and survival outcomes, including invasive breast cancer-free survival (IBCFS), distant recurrence-free survival (DRFS), and overall survival (OS) were analyzed., Results: The analysis included 799 female patients. The median age was 51 years (range, 23-79), and 51.6% (n=412) were premenopausal. Multifocality was confirmed in 17.3% (n=138), and estrogen receptor (ER) positivity in 29.8% (n = 238). Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab. With a median follow-up of 119.0 months (95% CI, 114.0-127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1-93.3), 97.5% (95% CI, 96.4-98.7), and 98.8% (95% CI, 98.0-99.6), respectively. No significant differences were observed between patients with and without adjuvant chemotherapy. The lack of differences in IBCFS by chemotherapy was consistent across subgroups, including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative disease., Conclusion: A clinically meaningful proportion of HER2-positive MIBC patients experience IBCFS events with long-term follow-up. Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration.

Background: Removal of intratracheal tumors is challenging due to the difficulty in securing a patent airway before surgery. We report a case of successful removal using jet ventilation with an injection-time-controllable manual jet ventilator., Case: A 3.3 cm long intratracheal mass was located 5 cm below the vocal cords and obstructing 70-80% of the trachea. Following induction, a rigid telescope under suspension laryngoscopy was used to guide the careful insertion of a hard and long catheter (inner diameter: 1.8 mm; outer diameter: 3 mm; length: 50 cm) beyond the tumor, enabling jet ventilation. The soft, lobulated mass was gradually excised using long forceps under endoscopic visualization. Anesthesia was maintained using total intravenous anesthesia. The operation lasted for 1 h and 45 min., Conclusions: This device ensured oxygenation and ventilation during the endoscopic removal of a large intratracheal tumor. This approach highlights its utility in managing challenging airway obstructions.

Adult spinal deformity (ASD) surgery aims to correct abnormal spinal alignment in both the sagittal and coronal planes to alleviate pain and improve functional activities of daily living. Despite the advancements in surgical techniques that have led to better clinical outcomes, postoperative mechanical complications remain. These complications include instrumentation failure, with proximal junctional kyphosis (PJK), proximal junctional failure (PJF), and rod fractures (RFs) being the most common. Such complications deteriorate clinical outcomes and often require revision surgery, which can be more burdensome for surgeons and patients, than index surgery. Thus, the risk factors for mechanical complications must be identified, and effective preventive strategies established. Therefore, this study aimed to review the risk factors for mechanical complications, focusing on PJK, PJF, and RF, and explore prevention strategies for these complications in ASD surgery, drawing upon recent literature.

High expression of externally injected in vitro transcribed (IVT) mRNA in natural killer (NK) cells is a prerequisite for NK cell-mediated cell therapy. To enhance the transfection efficacy of IVT mRNA-loaded polyplexes, we exposed NK cells to a hypertonic condition during transfection, which facilitated endo/exocytosis to maintain the isotonic state of the cells. The transfection efficacy of IVT mRNA was significantly enhanced after 24 h, which was mainly due to the facilitated cellular uptake and endosomal escape of the polyplexes. Interestingly, osmotic alterations in NK cells significantly affect the expression levels of endosome-escape-related genes in ion channels. Treatment with a mild hypertonic condition exhibited negligible toxicity to NK cells, without disturbing the integrity of the cellular membranes or the innate cytotoxic abilities of NK cells against cancer cells. These results demonstrate that the hypertonic treatment of NK cells enhances the transfection efficacy of IVT mRNA to produce genetically engineered NK cells.

Purpose: This study aimed to identify prognostic factors for retinal detachment (RD) and final best corrected visual acuity (BCVA) in acute retinal necrosis (ARN) patients using ultrawide-field (UWF) fundus imaging., Methods: This retrospective study included 29 eyes of 25 patients diagnosed with ARN. Clinical data, including symptom duration before presentation, initial and final BCVA, anterior chamber (AC) cell grade, and vitreous opacity grade, were collected. Based on the UWF fundus imaging, the presence of arterial obliteration and the extent of retinal necrosis were analyzed to identify risk factors for RD by categorizing patients into the RD and no RD groups., Results: The mean final BCVA was 0.72 ± 0.77 logarithm of the minimum angle of resolution (logMAR), and RD occurred in 20 eyes (70.0%). Final BCVA showed a significant difference between the RD and no RD groups. AC cell grade was significantly associated with both RD development and final BCVA (p = 0.035, p = 0.015, respectively). Arterial obliteration, fan-shaped necrotic lesions, and greater clock hours of retinitis were significantly related to RD development (p = 0.016, p = 0.001, p = 0.018, respectively). The retinitis zone was significantly correlated with final BCVA (p = 0.007). Additionally, BCVA before and at RD diagnosis showed a significant association with final BCVA., Conclusions: UWF imaging is useful for the prognosis prediction in ARN patients. Identifying characteristic UWF findings, such as arterial obliteration and extent of necrosis, can aid in predicting RD risk and visual outcomes, improving clinical management of ARN., Key Messages: WHAT IS KNOWN : Acute retinal necrosis (ARN) is a rapidly progressing inflammatory condition characterized by necrotizing retinitis and vasculitis. Retinal detachment (RD) is a common late complication of ARN, often leading to poor visual prognosis., What Is New: Ultrawide-field (UWF) imaging is useful for the prognosis prediction of ARN. UWF image analysis identified arterial obliteration, fan-shaped necrotic lesions, and an increased number of clock hours affected by retinitis as significant risk factors for the development of RD in ARN. Additionally, the zone of necrotic retinitis was strongly associated with the final best corrected visual acuity (BCVA) in ARN patients., Competing Interests: Declarations. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of Chonnam National University Hospital (IRB number: CNUH-2023–179). Informed consent: The Institutional Review Board of the Chonnam National University Hospital waived the need for informed consent, considering the use of de-identified patient data. Conflict of Interest: The authors have no proprietary or commercial interest in any materials discussed in this article., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Load-bearing fibrous tissues, like tendons, have remarkable strength with high water content (∼60%) due to the anisotropic network of collagen fibers. However, the scalability of biomimetic anisotropic hydrogels is limited by time-intensive fabrication processes involving cross-linking and stretching, often spanning several hours to days. Here, we present a rapid, scalable approach for fabricating tendon-mimetic hydrogel fibers within 1 min using the synergistic engineering of cyano- p -aramid nanofibers (CY-ANFs) and poly(vinyl alcohol) (PVA). Through continuous air-gap spinning, the formation of the anisotropic CY-ANF network drives instant gelation, producing hundreds of meters of hydrogel fibers without additional gelation treatment. From the perspective of properties, the hydrophilic PVA matrix affords flexibility, while the hydrophobic CY-ANF network provides a nonswelling feature and load-bearing ability, resulting in ultrastrong, water-rich hydrogel fibers. These hydrogel fibers exhibit a water content exceeding 80 wt %, along with exceptional strength (∼17.9 MPa), surpassing the mechanical properties of natural tendons (strength and modulus of approximately 10 and 100 MPa, respectively). Lengthy hydrogel fibers are integrated into larger-sized fabrics by knitting or weaving while also possessing strain-sensing capabilities. With excellent biocompatibility, these hydrogel fibers are promising candidates for artificial fibrous tissues and various biotechnological applications.

Importance: Physical activity (PA) is a nonpharmacological intervention for dementia prevention. The association between PA and Alzheimer disease (AD) plasma biomarkers remains underexplored., Objective: To investigate the associations among PA; plasma biomarkers, including β-amyloid 42/40 (Aβ42/40), phosphorylated-tau217 (ptau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL); and cognition., Design, Setting, and Participants: This cross-sectional study included participants with and without cognitive impairment recruited from multiple memory clinics in South Korea between May 2019 and May 2022. Data were analyzed from June to December 2024., Exposures: PA was assessed as metabolic equivalent task minutes per week using the International Physical Activity Questionnaire and categorized into quartiles from the lowest (Q1) to the highest (Q4)., Main Outcomes and Measures: Plasma Aβ42/40, ptau217, GFAP, and NfL were measured. Cognition was assessed using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB)., Results: Among 1144 participants (mean [SD] age 70.9 [8.7] years; 744 [65.0%] female), the highest PA quartile showed significantly lower ptau217 (estimate [SE], -0.14 [0.06]; P = .01) and NfL (estimate [SE], -0.12 [0.05]; P = .01) compared with the lowest quartile. Higher PA quartiles were associated with higher MMSE scores (estimate [SE]: Q2, 0.93 [0.31]; P = .003; Q3, 0.82 [0.32]; P = .009; Q4, 0.94 [0.32]; P = .004) and lower CDR-SB scores (estimate [SE]: Q2, -0.33 [0.16]; P = .04; Q3, -0.37 [0.16]; P = .02; Q4, -0.55 [0.16]; P = .001) after adjusting for age, sex, education years, and β-amyloid uptake. In subgroup analyses according to age and cognitive status, the associations of PA and plasma biomarkers with cognition were more pronounced in the older (age ≥65 years) and cognitively impaired groups compared with the younger and cognitively unimpaired groups., Conclusions and Relevance: These findings suggest that PA may help delay cognitive decline by modulating neurodegeneration and AD-specific tau pathologies. However, the cross-sectional design limits causal inference, and longitudinal studies are needed to confirm and clarify these associations.

Background: No established biomarker exists for specific myeloid cell populations or in gastric cancer. This study aimed to explore the prognostic and immunological relevance of plasma translationally controlled tumor protein (TCTP) in patients with advanced gastric cancer treated with an immune checkpoint inhibitor and/or cytotoxic chemotherapy., Methods: Plasma samples were prospectively collected from the cohorts of patients with gastric cancer treated with first-line fluoropyrimidine plus platinum chemotherapy (n=143, cohort 1) and third-line nivolumab (n=165, cohort 2). Plasma TCTP levels were quantified using ELISA, and multiplex proteomic analysis (Olink) was conducted to assess expression levels of immune-related proteins. External single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics datasets were employed to validate the findings., Results: Patients with high plasma TCTP levels (TCTP-high group) exhibited poor progression-free survival (PFS) and overall survival (OS) with first-line chemotherapy compared with those with low levels (TCTP-low group) in cohort 1 (HR: 1.73 for PFS; 1.77 for OS). In the TCTP-high group, proteins associated with immunosuppressive myeloid cells, angiogenesis, and immune exclusion of T/natural killer (NK) cell function were upregulated, whereas proteins involved in T-cell activation/exhaustion were significantly upregulated in the TCTP-low group. scRNA-seq analyses identified a myeloid subset with high TPT1 (encoding TCTP) expression and TCTP-related molecules, enriched with inhibitory myeloid inflammation gene signatures and providing inhibitory signals to T/NK cells (Macrophage-chemokine). Spatial transcriptomics analyses revealed a tumor-cell-enriched cluster co-localized with the Macrophage-chemokine subset, which exhibited the highest TPT1 expression and a positive correlation between its abundance and average TPT1 levels. In nivolumab-treated patients (cohort 2), the high TCTP group was associated with poor survival outcomes (HR: 1.39 for PFS; 1.47 for OS)., Conclusions: Plasma TCTP is a prognostic biomarker, reflecting clinically relevant immunosuppressive myeloid signals in patients with gastric cancer., Competing Interests: Competing interests: Nothing directly related to this work. Out of this work, M-HR received honoraria from DAEHWA Pharmaceutical, Bristol Myers Squibb, Lilly, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Novartis, Daiichi Sankyo, and AstraZeneca, and served as a consultant for DAEHWA Pharmaceutical, Bristol Myers Squibb, Lilly and Ono Pharmaceutical. H-DK received research grants from Roche/Genentech, Amgen, and AstraZeneca and honoraria from AstraZeneca, Bristol Myers Squibb, Ono Pharmaceuticals, Boryung Pharmaceuticals, MSD, Daiichi Sankyo, Astellas, Boostimmune, DAEHWA Pharmaceutical, LG Chem, and MustBio., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Lipid-based nanoparticles have emerged as promising drug delivery systems for a wide range of therapeutic agents, including plasmids, mRNA, and proteins. However, these nanoparticles still encounter various challenges in drug delivery, including drug leakage, poor solubility, and inadequate target specificity. In this comprehensive review, we present an in-depth investigation of four distinct drug delivery methods: liposomes, lipid nanoparticle formulations, solid lipid nanoparticles, and nanoemulsions. Moreover, we explore recent advances in lipid-based nanomedicines (LBNs) for organ-specific delivery, employing ligand-functionalized particles that specifically target receptors in desired organs. Through this strategy, LBNs enable direct and efficient drug delivery to the intended organs, leading to superior DNA or mRNA expression outcomes compared to conventional approaches. Importantly, the development of novel ligands and their judicious combination holds promise for minimizing the side effects associated with nonspecific drug delivery. By leveraging the unique properties of lipid-based nanoparticles and optimizing their design, researchers can overcome the limitations associated with current drug delivery systems. In this review, we aim to provide valuable insights into the advancements, challenges, and future directions of lipid-based nanoparticles in the field of drug delivery, paving the way for enhanced therapeutic strategies with improved efficacy and reduced adverse effects.

Purpose of the Report: This study investigated the prevalence and clinical characteristics of suspected non-Alzheimer disease pathophysiology (SNAP) across varying cognitive statuses and cerebral small vessel disease (CSVD) burden., Patients and Methods: We included 1992 participants with cognitive status categorized as cognitively unimpaired, mild cognitive impairment, or dementia. β-amyloid (Aβ, A) positivity was assessed by Aβ PET, and neurodegeneration (N) positivity was determined through hippocampal volume. Participants were further divided by the presence or absence of severe CSVD. The clinical and imaging characteristics of A-N+ (SNAP) group were compared with those of the A-N- and A+N+ groups., Results: SNAP participants were older and had more vascular risk factors compared with A-N- and A+N+ in the CSVD(-) cohort. SNAP and A+N+ showed similar cortical thinning. At the dementia stage, SNAP had a cognitive trajectory similar to A+N+ in the CSVD(-) cohort. However, SNAP exhibited less cognitive decline than A+N+ in the CSVD(+) cohort., Conclusions: SNAP is characterized by distinct clinical and imaging characteristics; however, it does not necessarily indicate a benign prognosis, particularly at the dementia stage. These findings highlight the need to assess SNAP in relation to the cognitive stage and CSVD presence to better understand its progression and guide interventions., Competing Interests: Conflicts of interest and sources of funding: This research was supported by a grant of the Korea Dementia Research Project through the Korea Dementia Research Center (KDRC), funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (grant number: RS-2020-KH106434 and RS-2020-KH107436); a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (grant number: RS-2022-KH127756 and RS-2022-KH125667); Future Medicine 2030 Project of the Samsung Medical Center [#SMX1250081]; the "Korea National Institute of Health" research project (2024-ER1003-01); partly supported by Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Korea government (MSIT) (No. RS-2021-II212068, Artificial Intelligence Innovation Hub); and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2019R1A5A2027340 and NRF-2020R1A2C1009778)., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

Several studies have revealed a possible association between antibiotic use and breast cancer in the Western population of women. However, its association with the Asian population remains unclear. Data utilized in this nationwide population-based retrospective cohort study were obtained from the Korean National Health Insurance Service database. The study population consisted of 4,097,812 women who were followed up from January 1, 2007, to December 31, 2019. Cox proportional hazards regression was utilized to calculate adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the risk of breast cancer according to cumulative days of antibiotic use and the number of antibiotic classes used. It was discovered that women who used antibiotics for more than 365 days had a higher risk of breast cancer (aHR, 1.15; 95% CI, 1.09-1.21) in comparison with those who did not use antibiotics. In addition, an association was found among women who used five or more classes of antibiotics, showing a higher risk of breast cancer (aHR, 1.11; 95% CI, 1.05-1.17) compared with nonusers. Furthermore, compared with antibiotic nonusers, only users of cephalosporins (aHR, 1.09; 95% CI, 1.02-1.17) and lincosamides (aHR, 1.70; 95% CI, 1.20-2.42) had a higher risk of breast cancer. These findings support epidemiologic evidence that long-term use of antibiotics may be associated with a higher risk of breast cancer. This underscores the need for further studies to address the potential for residual confounding, confirm causation, and elucidate the underlying mechanisms. Prevention Relevance: This study found a probable duration-dependent association between antibiotic prescriptions and breast cancer risk. The findings indicate that long-term antibiotic use could be associated with an increased risk of breast cancer and highlight the need for further research to confirm causality and mechanisms., (©2024 American Association for Cancer Research.)

Introduction: Pathogenic variants of annexin A11 (ANXA11) have been identified in patients with amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD). We explored ANXA11 pathogenic variants in a Korean FTD cohort to investigate the prevalence and the role of ANXA11 variation in FTD., Methods: We used next-generation sequencing (NGS) to search for pathogenic variants in ANXA11 in two nationwide FTD cohorts in Korea., Results: We identified a pathogenic variant in ANXA11, c.119A > G (p.D40G), in six patients with semantic variant primary progressive aphasia (svPPA), representing 5.5% of the svPPA cohort (6/109), and representing 2.3% of the FTD cohort overall (6/259). Only one patient later developed features suggestive of ALS., Discussion: This study links a rare variant in ANXA11 to a sporadic clinical syndrome in which specific TAR DNA-binding protein-43 (TDP-43) forms an obligate co-fibril with annexin A11. The variant, p.D40G, lies within the N-terminal portion of annexin A11's TDP-43 type C interacting domain, suggesting that genetic variation in that region may promote co-fibrillization., Highlights: The pathogenic variant of annexin A11 (ANXA11I) is linked to frontotemporal dementia (FTD) syndrome. ANXA11 (p.D40G) may be one of the possible genetic causes of semantic variant primary progressive aphasia (svPPA). ANXA11 (p.D40G) may enhance heteromeric amyloid filaments of annexin A11 and TDP-43, promoting frontotemporal lobar degeneration with TAR DNA-binding protein-43 (TDP-43) inclusions (FTLD-TDP) type C., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: We investigated the presence of impaired endothelial function in individuals with post-acute sequelae of coronavirus disease-2019 (PASC) compared to healthy individuals and explored the efficacy of combined exercise training in restoring or improving endothelial function in those with PASC., Methods: Study I was a cross-sectional study which compared endothelial function between individuals with PASC (n = 29, mean age 22.9 ± 3.9 year) and healthy individuals (n = 42, mean age 21.7 ± 2.0 year). Study II, an intervention design, explored if combined exercise training (n = 14) could reverse the decline in endothelial function associated with PASC compared to controls (n = 14). The combined exercise program included aerobic, resistance, and inspiratory muscle training administered for 8 weeks. We measured endothelial function using flow-mediated dilation of the brachial artery and assessed peak oxygen uptake (VO2peak), dyspnea, and fatigue before and after the intervention., Results: Individuals with PASC exhibited significantly lower endothelial function compared to healthy controls (4.95 ± 2.0% vs 8.00 ± 2.4%, P < .001). The exercise group showed a significant increase in endothelial function (4.73 ± 1.5% to 7.98 ± 2.4%) as opposed to the control group (5.31 ± 2.5% to 6.30 ± 2.5%) (interaction effect: P = .008), reaching levels similar to those in healthy individuals. Additionally, the exercise group demonstrated improvement in VO2peak (38.3 ± 6.4 ml/min/kg to 42.8 ± 7.3 ml/min/kg, P < .001) and a reduction in dyspnea and fatigue compared to the control group (P < .001)., Conclusions: Having PASC is associated with impaired endothelial function, but combined exercise training effectively restores it, making it a promising lifestyle intervention for vascular function in PASC., Competing Interests: All authors declare no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Hemoglobin (Hb) and heme, which are typically confined within red blood cells (RBCs), are essential for intravascular transport of gases and nutrients. However, these molecules acquire secondary functions upon exposure to the extracellular environment. Hb and heme generate reactive oxygen species (ROS), which are potent pro-inflammatory agents that contribute to oxidative stress and cellular damage. These events are relevant to neurodegenerative processes, where oxidative stress, irregular deposition of protein aggregates, and chronic inflammation are key pathological features. Extracellular Hb, heme, and oxidative stress derived from hemorrhagic events or RBC lysis may contribute to increased blood-brain barrier (BBB) permeability. These events allow Hb and heme to interact with neuroimmune cells and pathological protein aggregates, further amplifying pro-inflammatory signaling and the progression of Alzheimer's disease (AD) and Parkinson disease (PD). Chronic neuroinflammation, oxidative stress, and mitochondrial dysfunction lead to neuronal degeneration. Here, we sought to elucidate the pro-oxidative and inflammatory actions of extracellular Hb and heme, emphasizing their potential impact on AD and PD development.

Background: Allergen-specific immunotherapy (ASIT) is a highly effective treatment for atopic dermatitis. In humans, it has been reported to be significantly more effective than medication alone for the treatment of otitis media. ASIT can also be used in dogs, but it is not typically the first-line treatment for otitis externa and media., Objectives: This case report describes the successful management of refractory otitis media in a dog with frequent abscess recurrence following total ear canal ablation (TECA) using ASIT., Methods: A 9-year-old spayed female American Cocker Spaniel presented with a head tilt and a recurrent abscess adjacent to the left TECA site. A dermatological examination revealed secondary pyoderma. In open-mouth view radiography and CT, fluid in the tympanic bullae and lysis of the tympanic bullae wall were observed. The TECA was repeated twice and anti-inflammatory medication was administered, but the lesions reappeared. As a fundamental treatment, ASIT was included in the therapy., Results: After ASIT, the symptoms did not reoccur, even though the use of prednisolone was gradually reduced and discontinued over a period of two months. Currently, only ASIT has demonstrated progress in managing the patient's condition, even a year after discontinuing other medications. The patient's symptoms have not recurred and are well managed., Conclusions: A case of refractory otitis media, induced by atopic dermatitis, was effectively managed with ASIT over a prolonged period in a dog., (© 2025 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Measurable residual disease (MRD) is critical in guiding therapeutic strategies for B-cell acute lymphoblastic leukemia (B-ALL). This study evaluated the performance of a novel next-generation sequencing-based Celemics IGH assay (CM-IGH; Celemics, Seoul, Korea) compared with the LymphoTrack ® IGH FR1 assay (LT-IGH; Invivoscribe Technologies, USA) and multiparameter flow cytometry (MFC). A total of 31 diagnostic and 60 follow-up bone marrow aspirate samples, all from the same 31 pediatric patients with B-ALL, were analyzed using the CM-IGH and LT-IGH assays on the MiSeq platform, as well as MFC according to EuroFlow guidelines. Initial IGH clonality was detected in 83.9% of CM-IGH samples and 90.3% of LT-IGH samples ( p  = 0.060). MRD positivity rates in follow-up samples were 74.5% for CM-IGH, 61.1% for LT-IGH, and 56.7% for MFC. CM-IGH showed concordance rates of 78.3% with LT-IGH and 68.1% with MFC, while LT-IGH demonstrated an 81.5% concordance rate with MFC. The correlation coefficients ( r ) of MRD levels were 0.831 between CM-IGH and LT-IGH, 0.702 between CM-IGH and MFC, and 0.776 between LT-IGH and MFC. The CM-IGH assay demonstrates substantial concordance with LT-IGH and MFC in detecting MRD in pediatric patients with B-ALL, highlighting the complementary value of IGH clonality assays and MFC.

Oral lichen planus (OLP) is a chronic T cell-mediated inflammatory mucosal disease of unknown etiology. The lack of suitable animal models has hampered understanding of its etiopathogenesis. This study aimed to clarify the contribution of bacterial infection and zinc deficiency (ZD) in OLP pathogenesis by developing a murine model. Infection of human oral keratinocytes with OLP-isolated Escherichia coli 7.2 in the presence of a zinc chelator increased the intracellular survival of E. coli , likely due to the mitigation of zinc poisoning. C57BL/6 female mice were subjected to either a standard diet or a zinc-deficient diet for 1 mo. Their labial mucosa was then microdamaged through scratching, followed by oral administration of E. coli 7.2. Scratching alone triggered bacterial translocation to the epithelium and lamina propria, upregulated Mmp9 , increased immune responses in the cervical lymph nodes, and amplified CD4 + T-cell recruitment to labial mucosae. All these responses were intensified by E. coli infection, showing a strong synergism with ZD that shifted the Th cells infiltrating the labial mucosa in response to E. coli infection from Th1 to Th17 dominance. Repeated scratching plus E. coli infection amplified T-cell recruitment, even without ZD, leading to patchy lymphocytic infiltration, characterized by the presence of colloid bodies and disrupted basement membranes. Interestingly, Th1 blockade with anti-IFNγ and anti-IL-12 antibodies during E. coli infection hindered bacterial clearance in the epithelium and caused intense T-cell infiltration, epithelial degeneration and necrosis with colloid bodies, basement membrane destruction, and epithelial detachment, similar to erosive OLP lesions. This suggests that the Th1/IFNγ pathway may not be a suitable therapeutic target for OLP. In conclusion, OLP-like histopathology in the oral mucosa was induced through E. coli infection when combined with ZD, repeated epithelial microdamage, or Th1 blockade. This animal model provides a valuable platform for exploring specific hypotheses related to OLP pathogenesis and potential therapeutic targets., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: Retrospective review., Objectives: The International Spine Study Group-AO (ISSG-AO) Adult Spinal Deformity (ASD) Complication Classification System was developed to improve classification, reporting, and study of complications among patients undergoing ASD surgery. The ISSG-AO system classifies interventions to address complications by level of invasiveness: grade zero (none); grade 1, mild (e.g., medication change); grade 2, moderate (e.g., ICU admission); grade 3, severe (e.g., reoperation related to surgery of interest). To evaluate the efficacy of the ISSG-AO ASD Complication Classification System, we aimed to compare correlations between postoperative length of stay (LOS) and complication severity as classified by the ISSG-AO ASD and traditional major/minor complication classification systems., Methods: Patients age ≥18 in a multicenter ASD database who sustained in-hospital complications were identified. Complications were classified with the major/minor and ISSG-AO systems and correlated with LOS using an ensemble-based machine learning algorithm (conditional random forest) and a generalized linear mixed model., Results: 490 patients at 19 sites were included. 64.9% of complications were major, and 35.1% were minor. By ISSG-AO classification, 20.4%, 66.1%, 6.7%, and 6.7% were grades 0-3, respectively. ISSG-AO complication grading demonstrated significant correlation with LOS, whereas major/minor complication classification demonstrated inverse correlation with LOS. In conditional random forest analysis, ISSG-AO classification had the greatest relative importance when assessing correlations across multiple variables with LOS., Conclusions: The ISSG-AO system may help identify specific complications associated with prolonged LOS. Targeted interventions to avoid or reduce these complications may improve ASD surgical quality and resource utilization., 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.

There is no comprehensive umbrella review exploring the connection between schizophrenia and various health outcomes. Therefore, we aimed to systematically review existing meta-analyses about schizophrenia-associated comorbid health outcomes and validate the evidence levels. We performed an umbrella review of meta-analyses of observational studies to explore comorbid health outcomes in individuals with schizophrenia. Searches were conducted across PubMed/MEDLINE, EMBASE, ClinicalKey, and Google Scholar up to September 5, 2023, targeting meta-analyses of observational studies related to comorbid health outcomes in individuals with schizophrenia. We applied AMSTAR2 for data extraction and quality assessment, adhering to PRISMA guidelines. Evidence credibility was evaluated and categorized by evidence quality. Our protocol was registered with PROSPERO (CRD42024498833). Risk and protective factors were analyzed and presented through equivalent odds ratios (eRR). In this umbrella review, we analyzed 9 meta-analyses, including 88 original articles, covering 21 comorbid health outcomes with over 66 million participants across 19 countries. Patients with schizophrenia showed significant associations with multiple health outcomes, including asthma (eRR, 1.71 [95% CI, 1.05-2.78], class and quality of evidence [CE] = non-significant), chronic obstructive pulmonary disease (1.73 [1.25-2.37], CE = weak), pneumonia (2.63 [1.11-6.23], CE = weak), breast cancer of female patients (1.31 [1.04-1.65], CE = weak), cardiovascular disease (1.53 [1.12-2.11], CE = weak), stroke (1.71 [1.30-2.25], CE = weak), congestive heart failure (1.81 [1.21-2.69], CE = weak), sexual dysfunction (2.30 [1.75-3.04], CE = weak), fracture (1.63 [1.10-2.40], CE = weak), dementia (2.29 [1.19-4.39], CE = weak), and psoriasis (1.83 [1.18-2.83] CE = weak). Our study underscores the imperative for an integrated treatment approach to schizophrenia, highlighting its broad impact across respiratory, cardiovascular, sexual, neurological, and dermatological health domains. Given the predominantly non-significant to weak evidence levels, further studies are needed to reinforce our understanding., Competing Interests: Competing interests: The authors declare no competing interests. Ethics: An ethics statement is not applicable because this study is based exclusively on published literature. In its reporting, this manuscript follows PRISMA 2020 guideline., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Biodegradable polyesters provide an attractive alternative to non-degradable plastics but often encounter a tradeoff between biodegradability and mechanical properties because esters are rotational and lack hydrogen bonds. Conversely, natural polyamides, i.e., silk exhibit excellent mechanical strength because amides are non-rotational and form hydrogen bonds. Unlike esters, the nitrogen in amides can enhance microbial biodegradation. However, protein engineering exhibits limited productivity, and artificial polyamides, i.e., nylon remain non-degradable due to their hydrophobic nature. Herein, a method is proposed for developing poly(ester amide)s (PEA)s, a polyester and polyamide hybrid, to address prevailing production challenges. These materials are synthesized from upcycled monomers in a 10 L reactor and converted into films and yarns. They achieve a tensile strength of 109 MPa and tenacity of 5.0 g de -1 , while withstanding ironing temperatures. They achieve a remarkable 92% marine biodegradability in 12 months, which is rarely attained by current bioplastics, and exhibit low environmental impact in terms of greenhouse gas emissions. While biodegradable polyesters have remained within the performance range of commodity plastics, PEAs fall into the high-performance category, potentially reaching markets that existing biodegradable plastics have not, such as fishing lines and clothing., (© 2024 Wiley‐VCH GmbH.)

Background: North Korean refugees (NKRs) exhibit alarmingly high levels of depression prior to or immediately after entering South Korean society, which is likely attributable to their pre-migration traumatic experiences. However, prior research on NKRs has simply examined the cumulative effect of trauma on depression. Despite calls for research identifying trauma exposure patterns that co-occur among refugees, to date, no study has investigated distinct profiles of NKRs' pre-migration trauma exposure and their associations with depression in this high-risk population. To better understand the unique mental health needs of NKRs and provide them with tailored care, it is imperative to identify meaningful subgroups of NKRs with distinct profiles of trauma exposure., Aims: Using latent class analysis (LCA), which is a person-centered approach, this study aimed to identify subgroups of NKRs based on trauma exposure and their associations with sociodemographic characteristics and depression levels., Methods: A sample of NKRs ( N  = 405) in South Korea were assessed for depression, pre-migration trauma, and sociodemographic covariates through a self-administered survey. LCA was conducted to identify trauma exposure classes and multivariate ordinary least squares regression analysis was performed to examine associations between trauma exposure classes and depression., Results: The prevalence of clinically significant depression was 47.2% for our study sample. Three classes of trauma were identified: deprivation trauma and witnessing death (59.3%), complex and pervasive trauma (23.7%), and low exposure (17.0%). Members in the complex and pervasive trauma class demonstrated very high probabilities of exposure to all traumatic events and had the strongest association with elevated depression., Conclusions: Our findings underscore the importance of identifying subgroups of NKRs to unravel heterogeneity in trauma exposure and provide more nuanced explanations for different risk profiles regarding depression. These findings also provide evidence for a framework for clinicians to provide individualized resources and trauma-informed services to NKRs., Competing Interests: Conflict of interestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Recent studies suggest that ambient air pollution may contribute to osteoporosis; however, research focusing on populations with greater susceptibility is lacking. This study seeks to explore the association between air pollution and osteoporosis focusing on cancer survivors., Materials and Methods: We analyzed data from 8977 individuals (2245 cancer survivors, 6732 cancer-free population) obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) during 2007-2009 and 2015-2021. Air pollution exposures to PM 10 , PM 2.5 , SO₂, NO₂, and CO were estimated using air quality models and satellite data. Moving average concentrations over 1-3 years prior to the survey were calculated. Logistic regression models adjusting for demographic and lifestyle factors were used to assess the association between air pollution and osteoporosis status. Analyses were stratified by cancer survivorship status and sex., Results: Among cancer survivors, particularly female cancer survivors, higher long-term exposure to air pollutants was associated with greater odds of osteoporosis. Cancer survivors exposed to higher PM 10 over 1-, 2-, and 3-year periods had greater odds of osteoporosis (all p < 0.05). In female cancer survivors, 1-year exposure to PM 2.5 was associated with 25 % higher odds of osteoporosis (OR = 1.25, 95 % CI = 1.02-1.54), and NO₂ exposure showed a similar association (OR = 1.42; 95 % CI = 1.06-1.90). These associations were not observed in the individuals without cancer history., Conclusion: The association between air pollution and osteoporosis was observed in cancer survivors, especially among female cancer survivors. Our findings emphasize the need for targeted interventions for at-risk populations such as cancer survivors., 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 © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Urinalysis, an essential diagnostic tool, faces challenges in terms of standardization and accuracy. The use of artificial intelligence (AI) with mobile technology can potentially solve these challenges. Therefore, we investigated the effectiveness and accuracy of an AI-based program in automatically interpreting urine test strips using mobile phone cameras, an approach that may revolutionize point-of-care testing., Methods: We developed novel urine test strips and an AI algorithm for image capture. Sample images from the Chungnam National University Sejong Hospital were collected to train a k-nearest neighbor classification algorithm to read the strips. A mobile application was developed for image capturing and processing. We assessed the accuracy, sensitivity, specificity, and ROC area under the curve for 10 parameters., Results: In total, 2,612 urine test strip images were collected. The AI algorithm demonstrated 98.7% accuracy in detecting urinary nitrite and 97.3% accuracy in detecting urinary glucose. The sensitivity and specificity were high for most parameters. However, this system could not reliably determine the specific gravity. The optimal time for capturing the test strip results was 75 secs after dipping., Conclusions: The AI-based program accurately interpreted urine test strips using smartphone cameras, offering an accessible and efficient method for urinalysis. This system can be used for immediate analysis and remote testing. Further research is warranted to refine test parameters such as specific gravity to enhance accuracy and reliability.

Excessive adipocyte differentiation and accumulation contribute to the development of metabolic disorders. Growth differentiation factor 15 (GDF15) plays an essential role in energy homeostasis and is considered an anti-obesity factor; however, elevated serum levels of endogenous GDF15 have been reported in certain individuals with obesity. In this study, to gain a better understanding of this complex relationship between GDF15 levels and obesity, we investigated GDF15 expression and function during adipogenesis. Compared with mice fed a normal diet, those fed a short-term high-fat diet exhibited a reduction in epididymal white adipose tissue and serum GDF15 expression. These results were confirmed in human adipose-derived stem cells that showed reduced GDF15 expression during adipogenesis differentiation. During adipogenesis, GDF15 was primarily degraded via the autophagy lysosomal pathway, and GDF15 overexpression in pre-adipocytes inhibited adipogenesis by suppressing CCAAT enhancer binding protein alpha (C/EBPα). Furthermore, whereas we detected a reduction in homologous-pairing protein 2 (HOP2) expression during adipogenesis, expression increased in response to an overexpression of GDF15. Furthermore, following knockdown of HOP2 during GDF15 overexpression, there was no suppression of C/EBPα expression. These findings indicate that GDF15 undergoes lysosomal degradation via an autophagic pathway and suppresses adipocyte differentiation via the HOP2-mediated inhibition of C/EBPα expression. Collectively, our findings indicate that GDF15 could serve as a potential therapeutic target for the treatment of metabolic disorders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interestsKim Chul Ho reports financial support was provided by Korea Health Industry Development Institute. Kim Chul Ho reports financial support was provided by National Research Foundation of Korea. If there are other authors, they 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 © 2025. Published by Elsevier B.V.)

Study Design: Multicenter comparative cohort., Objective: Studies have shown markedly higher rates of complications and all-cause mortality following surgery for adult cervical deformity (ACD) compared with adult thoracolumbar deformity (ATLD), though the reasons for these differences remain unclear. Our objectives were to compare baseline frailty, disability, and comorbidities between ACD and complex ATLD patients undergoing surgery., Methods: Two multicenter prospective adult spinal deformity registries were queried, one ATLD and one ACD. Baseline clinical and frailty measures were compared between the cohorts., Results: 616 patients were identified (107 ACD and 509 ATLD). These groups had similar mean age (64.6 vs 60.8 years, respectively, P = .07). ACD patients were less likely to be women (51.9% vs 69.5%, P < .001) and had greater Charlson Comorbidity Index (1.5 vs .9, P < .001) and ASA grade (2.7 vs 2.4, P < .001). ACD patients had worse VR-12 Physical Component Score (PCS, 25.7 vs 29.9, P < .001) and PROMIS Physical Function Score (33.3 vs 35.3, P = .031). All frailty measures were significantly worse for ACD patients, including hand dynamometer (44.6 vs 55.6 lbs, P < .001), CSHA Clinical Frailty Score (CFS, 4.0 vs 3.2, P < .001), and Edmonton Frailty Scale (EFS, 5.15 vs 3.21, P < .001). Greater proportions of ACD patients were frail (22.9% vs 5.7%) or vulnerable (15.6% vs 10.9%) based on EFS ( P < .001)., Conclusions: Compared with ATLD patients, ACD patients had worse baseline characteristics on all measures assessed (comorbidities/disability/frailty). These differences may help account for greater risk of complications and all-cause mortality previously observed in ACD patients and facilitate strategies for better preoperative optimization., 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: Lower functioning and higher symptom severity are observed when panic disorder (PD) co-occurs with generalized anxiety disorder (PD + GAD). No research on cortical gyrification patterns in the PD + GAD group has been conducted to date, which could show the alterations in brain connectivity in the extended fear network (EFN). This study aimed to investigate the characteristics of cortical gyrification in the PD + GAD group, compared to that in the PD without comorbid GAD (PD-GAD) group., Methods: This study included 90 patients with PD, with propensity score matching between the PD + GAD (n = 30) and PD-GAD groups (n = 60), and 65 healthy controls (HC). For clinical evaluation, we assessed the anxiety symptomatology, suicidality, and harm avoidance. The local gyrification index (LGI) was obtained from T1-weighted brain MRI data using FreeSurfer., Results: In the PD group compared to the HC, the hypergyrification involved the EFN. In the PD + GAD group compared to the PD-GAD group, hypergyrification was shown in the pathological worry-related brain regions. Within the PD + GAD group, significant positive correlations were observed between the superior frontal gyrus LGI values and suicidality scores, as well as between the superior parietal gyrus LGI values and harm avoidance levels., Limitations: Given the variability in cortical gyrification patterns, longitudinal studies are needed to assess the occurrence of hypergyrification in specific brain regions., Conclusions: This study is the first to demonstrate cortical gyrification patterns in the PD + GAD group compared to those in the PD-GAD group. Notably, the EFN and pathological worry-related brain regions have been implicated in the pathology of PD + GAD., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Study Design: Cross-sectional survey., Objective: Although literature does not recommend routine wound drain utilization, there is a disconnect between the evidence and clinical practice. This study aims to explore into this controversy and analyze the surgeon preferences related to drain utilization, and the factors influencing drain use and criterion for removal., Methods: A survey was distributed to AO Spine members worldwide. Surgeon demographics and factors related to peri-operative drain use in 1 or 2-level open fusion surgery for lumbar degenerative pathologies were collected. Multivariate analyses by drain utilization, and criterion of removal were conducted., Results: 231 surgeons participated, including 220 males (95.2%), orthopedics (178, 77.1%), and academic/university-affiliated (114, 49.4%). Most surgeons preferred drain use (186, 80.5%) and subfascial drains (169, 73.2%). Drains were removed based on duration by 52.87% of the surgeons, but 27.7% removed drains based on outputs. On multivariable analysis, significant predictors of drain use were surgeon's aged 35-44 (OR = 11.9, 95% CI = 1.2-117.2, P = .034), 45-54 (29.1, 3.1-269.6, P = .003), 55-64 (8.9, 1.4-56.5, .019), and wound closure using coaptive films (6.0, 1.2-29.0, P = .025). Additionally, surgeons from Asia Pacific (OR = 5.19, 95% CI = 1.65-16.38, P = .005), Europe (3.55, 1.22-10.31, P = .020), and Latin America (4.40, 1.09-17.83, .038) were more likely to remove drain based on time duration, but surgeons <5 years of experience (10.23, 1.75-59.71, P = .010) were more likely to remove drains based on outputs., Conclusions: Most spine surgeons worldwide prefer to place a subfascial wound drain for degenerative open lumbar surgery. The choice for drain placement is associated with the surgeon's age and use of coaptive films for wound closure, while the criterion for drain removal is associated with the surgeons' region of practice and experience., 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.

This study discovered the first Asian population of Sphaeroforma nootkatensis (SphX), a member of Mesomycetozoea, in the southern coastal region of South Korea. Although investigating parasites in Pacific oysters (Crassostrea gigas), a single-cell microorganism was isolated from gill tissues. Comprehensive phylogenetic analysis of its 18S rDNA revealed its placement within the order Ichthyophonida, class Mesomycetozoea. SphX formed a distinct cluster within Sphaeroforma spp., separate from Pseudoperkinsus tapetis. Morphological examinations of in vitro cultured cells revealed two distinctive life stages characterized by multilobe and granular sporangium, accompanied by corresponding non-motile larger and motile smaller endospores, respectively. Scanning electron microscope analysis depicted lobular and smooth surfaces on vegetative cells, indicative of differing life cycle stages. Transmission electron microscope observations revealed intriguing features consistent with previous reports on Mesomycetozoea. A prominent fibrillar structure was noted in a vegetative cell. In contrast, smaller endospores were observed with cilia-like structures surrounding the cell wall, indicating their mode of movement. The Ray's fluid thioglycollate medium assay showed that SphX cells were digested, whereas some small endospores remained resistant. This discovery provides novel insights into the life stages of Mesomycetozoans and geographical distribution and underscores the importance of monitoring oyster health for effective aquaculture management., Competing Interests: Declaration of competing interest The author declares 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 GmbH. All rights reserved.)

Objectives: To determine the difference of body composition change measured by bioelectrical impedance analysis (BIA) between singleton and twin pregnancy., Study Design: A prospective study was performed in pregnant women admitted to maternal-fetal intensive care unit in Seoul National University Bundang Hospital from June to August 2023. Twenty one patients were enrolled (9 singleton and 12 twin pregnancies) and underwent BIA at the admission. Maternal obstetric baseline characteristics were reviewed., Results: There was no statistical difference between singleton and twin pregnancies in terms of maternal age and gestational ages at the tests and other obstetric complications. The phase angle was significantly lower in twin pregnancies than in singleton pregnancies (5.1° vs. 6.2°, p = 0.007) and the difference was more distinct in the lower extremities (right; left; both; p < 0.05). The mean values of total body water (TBW), intracellular water (ICW), and extracellular water (ECW) measured in the whole body, trunk, and extremities were not statistically different between the twin and singleton pregnancy groups; however, the ratio of ECW to TBW was significantly higher in twin pregnancies than in singleton pregnancies (0.40 vs. 0.39, p = 0.001). All ECW/TBW ratios measured in the trunk and extremities presented with the same results as ECW/TBW ratios measured in the whole body (all: p < 0.05). The T-score was significantly higher in the twin group than in the singleton group (4.4 vs. 1.2, p = 0.001)., Conclusions: Twin pregnancies had a lower phase angle and higher ECW/TBW ratio compared to singleton pregnancies., 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 © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Triboelectric nanogenerators (TENGs) have gained significant attention for ability to convert mechanical energy into electrical energy. As the applications of TENG devices expand, their safety and reliability becomes priority, particularly where there is risk of fire or spontaneous combustion. Flame-retardant materials can be employed to address these safety concerns without compromising the performance and efficiency of TENGs. The primary focus of this review is on flame-retardant materials, including polymers, biomaterials, liquid polymers, aerogels, and carbon-based materials. The fundamental properties of these materials for TENG applications are elucidated. The characteristics of each material type are described, along with their potential to boost the safety and performance of TENGs. The importance of flame retardancy in advancing TENG technology can be projected from its usage in wearable electronics, self-powered sensors, and smart textiles. Current challenges such as material compatibility, fabrication complexity, and environmental concerns are addressed, along with proposed strategies for overcoming them. This review underscores the significance of flame-retardant materials in strengthening the functionality and safety of TENG devices, paving the way for their widespread adoption across various industries., (© 2025 Wiley‐VCH GmbH.)

Study Design: This is a retrospective case-control study., Objectives: The objectives of this study are to identify (1) risk factors for delayed ambulation following adult spinal deformity (ASD) surgery and (2) complications associated with delayed ambulation., Methods: One-hundred and ninety-one patients with ASD who underwent posterior-only fusion (≥5 levels, LIV pelvis) were reviewed. Patients who ambulated with physical therapy (PT) on POD2 or later (LateAmb, n = 49) were propensity matched 1:1 to patients who ambulated on POD0-1 (NmlAmb, n = 49) based on the extent of fusion and surgical invasiveness score (ASD-S). Risk factors, as well as inpatient medical complications were compared. Logistic regressions were used to identify risk factors for late ambulation., Results: Of the patients who did not ambulate on POD0-1, 32% declined participation secondary to pain or dizziness/fatigue, while 68% were restricted from participation by PT/nursing due to fatigue, inability to follow commands, nausea/dizziness, pain, or hypotension. Logistic regression showed that intraoperative estimated blood loss (EBL) >2L (OR = 5.57 [1.51-20.55], P = .010) was independently associated with an increased risk of delayed ambulation, with a 1.25 times higher risk for every 250 mL increase in EBL ( P = .014). Modified 5-Item Frailty Index (mFI-5) was also independently associated with delayed ambulation (OR = 2.53 [1.14-5.63], P = .023). LateAmb demonstrated a higher hospital LOS (8.4 ± 4.0 vs 6.2 ± 2.6, P < .001). The LateAmb group trended toward an increase in medical complications on POD3+ (14.3% vs 26.5%, P = .210)., Conclusions: EBL demonstrates a dose-response relationship with risk for delayed ambulation. Delayed ambulation increases LOS and may impact medical complications., 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: TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53 -mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53 -mutated MDS and AML, focusing on diagnostic aspects based on updated classifications., Methods: This study included patients aged ≥ 18 yrs who were diagnosed as having MDS (N=1,244) or AML (N=2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53 , were collected and analyzed., Results: TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF >50% for the 5th WHO classification and the presence of a complex karyotype for the ICC., Conclusions: Collectively, we elucidated the molecular genetic characteristics of patients with TP53 -mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.

Background: Previous studies have used machine learning to identify clinically relevant atrophic regions in progressive supranuclear palsy (PSP). This study applied Elastic Net (EN) in PSP to uncover key atrophic patterns, offering a novel approach to understanding its pathology., Methods: This study included baseline data from 74 patients with PSP enrolled in the Study of Comprehensive ANd multimodal marker-based cohort of PSP (SCAN-PSP, NCT05579301) in Seoul between January 2022 and August 2023. Participants were evaluated with PSP-rating scale (PSPRS) and Schwab & England Activity of daily living (SEADL). EN regression was used to identify regions with high explanatory power for clinical outcomes, which were combined with clinical parameters to build prediction models. Features selected from EN classification were applied to discriminate between the two groups., Results: EN identified the third ventricle, right anterior cingulate cortex, and left lateral orbitofrontal cortex as significant features, and multivariate linear regression models incorporating these regions with clinical variables showed high explainability for PSPRS (adjusted R 2  = 0.62) and SEADL (adjusted R 2  = 0.74). The EN-predicted values demonstrated strong correlation with actual scores of PSPRS (r = 0.75, p = 2·10 -14 ) and SEADL (r = 0.82, p = 2·10 -19 ). The combined EN-selected features and clinical parameters model robustly distinguished PSP-Richardson from the subcortical types (AUC = 0.94) and those with severe downgaze palsy from without (AUC = 0.90)., Conclusion: This study demonstrated that EN effectively identified significant regional atrophies in PSP, with a modest sample size. Future studies could incorporate multimodal analysis to identify markers for monitoring disease progression., 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 © 2025 Elsevier Ltd. All rights reserved.)

Schizophrenia and attention deficit hyperactivity disorder (ADHD) have many contradicting features, but both these disorders share inattention as a core symptom. This study explored how the characteristics of inattention differ between the two disorders. 20 patients with schizophrenia, 20 patients with adult ADHD and 20 healthy controls participated in this study. Comprehensive attention test, Korean Wechsler adult intelligence scale-IV and resting-state functional magnetic resonance imaging (fMRI) were collected, among other things. The schizophrenia and ADHD groups showed low and high levels of functional connectivity in the default mode network (DMN), respectively. Functional connectivity level within the DMN was also positively correlated with processing speed index in the schizophrenia group and positively correlated with the number of divided-attention commission errors in the ADHD group. These results show that schizophrenia and adult ADHD have similarities in the characteristics of attention deficit, in that both may arise from dysregulation within the DMN. However, the differences in the levels of functional connectivity in the DMN between these groups affect how inattention manifests in each group., Competing Interests: Declaration of competing interest There is no conflict of interest to declare., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Precise and predictable genetic elements are required to address various issues, such as suboptimal metabolic flux or imbalanced protein assembly caused by the inadequate control of polycistronic gene expression in bacteria. Here, we devised a synthetic biopart based on the translational coupling to control polycistronic gene expression. This module links the translation of genes within a polycistronic mRNA, maintaining their expression ratios regardless of coding sequences, transcription rate, and upstream gene translation rate. By engineering the Shine-Dalgarno sequences within these synthetic bioparts, we adjusted the expression ratios of polycistronic genes. We created 41 bioparts with varied relative expression ratios, ranging from 0.03 to 0.92, enabling precise control of pathway enzyme gene expression in a polycistronic manner. This led to up to a 7.6-fold increase in the production of valuable biochemicals such as 3-hydroxypropionic acid, poly(3-hydroxybutyrate), and lycopene. Our work provides genetic regulatory modules for precise and predictable polycistronic gene expression, facilitating efficient protein assembly, biosynthetic gene cluster expression, and pathway optimization., Competing Interests: Declaration of competing interest All other authors declare they have no competing interests., (Copyright © 2024 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

This study assessed the performance of the Allplex TM stx1/2/2a/2d Typing (ASTXT) assay (Seegene) for diagnosis and typing Shiga toxin-producing Escherichia coli. Analytical sensitivity and specificity were evaluated using 18 spiked strains, and cross-reactivity was tested on 114 strains including E. coli without Shiga toxin. Clinical performance was evaluated using the proficiency panels and 76 stool samples. Analytical sensitivity was revealed to 4.14 log 10 CFU ml -1 for E. coli strain with stx1, 4.47 log 10 CFU ml -1 for strain with stx2, 4.03 log 10 CFU ml -1 for strain with stx2a, and 4.02 log 10 CFU ml -1 for strain with stx2d, respectively. Imprecisions were within 5 % and cross-reactivity was not observed. The ASTXT assay showed perfect agreement with the proficiency panel results and achieved 100 % positive and negative percent agreement using clinical stool samples. The ASTXT assay demonstrated reliable performance for the rapid detection and typing of Shiga toxin-producing E. coli in human stool samples., 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Glucocorticoids have been used to treat inflammatory diseases because of their potent anti-inflammatory and immunosuppressive actions. However, chronic use of high levels of glucocorticoids causes several adverse effects, limiting their clinical utility. Here, we explored the therapeutic potential of a combination treatment involving reduced concentrations of rapamycin, an autophagy activator and immunosuppressant, and glucocorticoids in an animal model of Parkinson's disease (PD). In vitro experiments with the SH-SY5Y cell line revealed that 10 μM rapamycin significantly increased the survival rate of cells treated with 6-hydroxydopamine to induce cell death, while both dexamethasone and prednisone at 50 μM exhibited an evident increase in survival rates. The combination treatment with reduced concentrations (rapamycin: 5 μM, dexamethasone: 25 μM) showed a more effective recovery in survival than singular treatments with high concentrations of rapamycin, prednisone, or dexamethasone. Propidium iodide-staining confirmed the efficacy of the combination treatment. This treatment did not significantly alter forkhead box O3a (FOXO3a)-triggered apoptosis and autophagic flux but upregulated the expression of the anti-apoptotic protein B-cell lymphoma 2, while B-cell lymphoma-extra-large showed no significant change. In vivo experiments using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD animal model revealed that the combination treatment effectively mitigated defects in motor function. The combination treatment completely blocked the loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta and partially prevented the reduction of TH-positive fibers in the striatum caused by the MPTP treatment. It also reduced the microglial levels caused by the MPTP treatment. Although not significant, it demonstrated an increase in survival rates of MPTP-induced PD model mice. In conclusion, the combination treatment with reduced concentrations of rapamycin and glucocorticoids may serve as potential therapy for PD, albeit further research and clinical trials are warranted to validate its efficacy and safety., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there are no conflicts of interest., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Nowadays, consent to use donor bodies for medical education and research is obtained from the body donors and their families before the donation. Recently, the International Federation of Associations of Anatomists (IFAA) published guidelines that could restrict the appearance of cadaveric images in commercial anatomical resources such as textbooks and other educational products. These guidelines state that the donor must expressly consent to using such images for this purpose. Cadaveric photos and drawings made from dissections of cadavers have been used in anatomy textbooks and atlases for hundreds of years. They are invaluable for anatomy students and clinical/surgical practitioners. The IFAA guidelines should not restrict the use of those older books; to do so would infringe the rights of those seeking knowledge from these resources. As the images in such textbooks and atlases are anonymized and are used for teaching and research, and the donors and their families are informed about this before the donation, we believe no additional consent is needed. It is impossible to separate educational from "commercial" usage entirely in any situation, e.g., publications from publishers and the use of cadavers in medical schools. Therefore, our best efforts to avoid unethical use of cadaveric images by following traditional consent processes are still needed so that more people will reap the benefits from them. As senior textbook/atlas authors/editors from over 10 countries, we believe that using cadaveric images in anatomy textbooks is appropriate, and no additional consent should be necessary. Such usage falls within the good faith of professionals using these invaluable gifts., (© 2025 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Study Design: Reliability analysis., Objectives: Vertebral pelvic angles (VPA) are gaining popularity given their ability to describe the shape of the spine. Understanding the reliability and minimal detectable change (MDC) is necessary to determine how these measurement tools should be used in the manual assessment of spine radiographs. Our aim is to assess intra- and interobserver intraclass correlation coefficients (ICC) and the MDC in the use of VPA for assessing alignment in adult spinal deformity (ASD)., Methods: Three independent examiners blindly measured T1, T4, T9, L1, and L4PA twice in ASD patients with a 4-week window after the initial measurements. Patients who had undergone hip or shoulder arthroplasty, fused or transitional vertebrae, or whose hip joints were not visible on radiographs were excluded. Power analysis calculated a minimum sample size of 19. Both intra- and interobserver ICC and MDC, which denotes the smallest detectable change in a true value with 95% confidence, were calculated., Results: Out of the 193 patients, 39 were ultimately included in the study, and 390 measurements were performed by 3 raters. Intraobserver ICC values ranged from .90 to .99. The interobserver ICC was .97, .97, .96, .95, and .92, and the MDC was 5.3°, 5.1°, 4.8°, 4.9°, and 4.1° for T1, T4, T9, L1, and L4PA, respectively., Conclusion: All VPAs showed excellent intra- and interobserver reliability, however, the MDC is relatively high compared to typical ranges for VPA values. Therefore, surgeons must be aware that substantial alignment changes may not be detected by a single VPA., 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.

Identifying the molecules that control neural stem cell (NSC) fate would revolutionize treatment strategies for neurodegenerative diseases. Histone lysine demethylase 1A (KDM1A) demethylates the mono- and di-methyl groups of histone 3 lysine 4 (H3K4) and H3K9 and plays an essential role in NSC proliferation. In this study, we investigated the effects of Seclidemstat (SP-2577), a reversible KDM1A inhibitor, and tranylcypromine (TCP), a monoamine oxidase inhibitor and recently known as an irreversible histone lysine demethylase 1A inhibitor, on NSCs. SP-2577 and TCP increased glial fibrillary acidic protein expression (GFAP), decreased βIII-tubulin (TUBB3) expression, and phosphorylated signal transducer and activator of transcription 3 (STAT3) in rat NSCs. SP-2577 and TCP enhanced the transcription of Gfap and reduced Tubb3 transcription. Furthermore, SP-2577 increased the transcription levels of interleukin-6 and leukemia inhibitory factor, while TCP induced the transcription level of fibroblast growth factor 2. Therefore, we show that the KDM1A inhibitors, SP-2577 and TCP, induce astrocytogenesis in rat NSCs. These findings suggest that KDM1A is a target for regulating NSCs fate and provide insights into the molecular mechanisms underlying neurodevelopmental processes and epigenetics., 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 © 2025. Published by Elsevier Inc.)

Geographical origin authentication of onions has become significant owing to origin labelling fraud in South Korea. Various analytical techniques based on stable isotope ratios, organic and inorganic constituents, or their combinations, can distinguish agricultural products geographically. However, studies on the geographical classification of South Korean and Chinese onions using stable isotopes and minerals remain scarce. This study aimed to discriminate geographically between South Korean and Chinese onions using stable isotope ratios (δ 13 C, δ 15 N, and δ 34 S) and mineral contents (K, Ca, Mg, Na, P, Fe, Zn, Mn, Cu, and Sr) combined with multivariate statistical analysis. Fifty-eight onion samples cultivated in South Korea and China were collected in 2023. The two stable isotope ratios (δ 15 N and δ 34 S) and six minerals (K, Ca, Na, Fe, Zn, and Sr) significantly differed between these onions. These variables were applied in orthogonal partial least squares discriminant analysis to classify the onion samples regionally. The predictive ability and goodness-of-fit parameters ( R 2 X and R 2 Y ) were 0.671, 0.383, and 0.677, respectively. K, Sr, δ 34 S, and Na served as potential markers contributing to the classification. Therefore, stable isotopes and mineral elements may serve as effective indicators for the geographical discrimination of South Korean and Chinese onion samples using multivariate analyses.

Study Design: Retrospective review of prospective multicenter data., Objectives: This study aimed to investigate the shape of TK before and after fusion in ASD patients treated with long fusion., Methods: ASD patients undergoing posterior spinal fusions including at least T5 to L1 without prior fusion extending to the thoracic spine were included. Patients were categorized based on the preoperative T1-T12 kyphosis into: Hypo-TK (if < 30°), Normal-TK, and Hyper-TK (if > 70°). Regional kyphosis at T10-L1 (Distal), T5-T10 (Middle), and T1-T5 (Proximal) and their relative contributions to total kyphosis were compared between groups, and the pre-to postoperative changes were investigated using paired t test., Results: In total, 329 patients were included in this analysis (mean age: 57 ± 16 years, 79.6% female). Preoperative T1-T12 TK for the entire cohort was 40.9 ± 2° (32% Hypo-TK, 11% Hyper-TK, 57% Normal-TK). The Hypo-TK group had the smallest distal TK (5.9 vs 17.1 & 26.0), and middle TK (8.0 vs 25.3 & 45.4), but the percentage of contribution to total kyphosis was not significantly different (Distal: 24.1% vs 34.1% vs 32.8%; Middle: 46.6% vs 53.9% vs 56.8%, all P > .1). Postoperatively, T1-12 TK increased significantly (40.9 ± 2.0° vs 57.8 ± 17.6°). Each group had a decrease in distal kyphosis (Hypo-TK 2.6 ± 10.4°; Normal-TK 8.9 ± 11.5°; Hyper-TK 14.9 ± 12°, all P < .05). The middle kyphosis significantly decreased for Hyper-TK (11.8 ± 12.4) and increased for both Normal-TK and Hypo-TK (3.8 ± 11° and 14.2 ± 11°). Proximal TK increased significantly for all groups by 14-18°. Deterioration from Normal-TK to Hyper-TK postoperatively was associated with lower rate of patient satisfaction (59.6% vs 77.3%, P = .032)., Conclusions: Posterior spinal fusion for ASD alters the magnitude and shape of thoracic kyphosis. While 60% of patients had a normal TK at baseline, 30% of those patients developed iatrogenic hyperkyphosis postoperatively. Patients with baseline hypokyphosis were more likely to be corrected to normal TK than hyperkyphotic patients. Future research should investigate TK restoration in ASD and its impact on clinical outcomes and complications., 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.