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Kuey teow is one of the delicacies of Guangdong, China and is a gluten-free noodle dish made from rice. It has a short storage period and extending the shelf life by quick freezing induces quality deterioration due to temperature fluctuations. To improve its freeze-thaw frozen storage quality, this paper examined the effects of hydroxypropyl corn starch (HCS), guar gum (GG), and compound phosphates (CP) on the quality of quick-frozen kuey teow during freeze-thaw cycles. The mechanism was investigated by identifying changes in the moisture status, aging degree of the starch, and textural and cooking characteristics. The results showed that all three additions improved the toughness, chewiness and steaming characteristics of the kuey teow, with CP significantly enhancing chewiness. XRD and FTIR results revealed that GG more significantly inhibited the decrease of starch crystallinity, while HCS inhibited starch aging. GG, HCS and CP all improved the hydration characteristics and water holding capacity of rice starch. GG enhances the ability of starch to bind more tightly with water, resulting in a more uniform water distribution and a more continuous and tight structure of the kuey teow. This study will provide a theoretical basis for compounding and optimizing the quick-freezing of kuey teow., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background and Aims: Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment. IgA contributes to inflammation and dismantling antitumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in Pil Soo Sung the tumor microenvironment of HCC., Approach and Results: CAF dynamics in HCC tumor microenvironment were analyzed through single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro. Progression-free survival of patients with advanced HCC treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels ( p <0.05). Single-cell analysis showed that subcluster proportions in the CAF-fibroblast activation protein-α matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of fibroblast activation protein in the CD68 + cells from patients with high serum IgA levels ( p <0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 expression levels than those in mock-treated CAFs ( p <0.05). Coculture with CAFs attenuated the cytotoxic function of activated CD8 + T cells. Interestingly, activated CD8 + T cells cocultured with IgA-treated CAFs exhibited increased programmed death-1 expression levels than those cocultured with mock-treated CAFs ( p <0.05)., Conclusions: Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T-cell function. Our study highlighted their potential roles in tumor progression and immune suppression., (Copyright © 2024 American Association for the Study of Liver Diseases.)

The hypothalamus plays an important role in aging, but it remains unclear regarding the underlying epigenetics and whether this hypothalamic basis can help address aging-related diseases. Here, by comparing mouse hypothalamus with two other limbic system components, we show that the hypothalamus is characterized by distinctively high-level DNA methylation during young age and by the distinct dynamics of DNA methylation and demethylation when approaching middle age. On the other hand, age-related DNA methylation in these limbic system components commonly and sensitively applies to genes in hypothalamic regulatory pathways, notably oxytocin (OXT) and gonadotropin-releasing hormone (GnRH) pathways. Middle age is associated with transcriptional declines of genes which encode OXT, GnRH and signaling components, which similarly occur in an Alzheimer's disease (AD)-like model. Therapeutically, OXT-GnRH combination is substantially more effective than individual peptides in treating AD-like disorders in male 5×FAD model. In conclusion, the hypothalamus is important for modeling age-related DNA methylation and developing hypothalamic strategies to combat AD., (© 2024. The Author(s).)

The central nervous system (CNS), despite the presence of strategically positioned anatomical barriers designed to protect it, is not entirely isolated from the immune system 1,2 . In fact, it remains physically connected to and can be influenced by the peripheral immune system 1 . How the CNS retains such responsiveness while maintaining an immunologically unique status remains an outstanding conundrum. In searching for molecular cues that derive from the CNS and allow its direct communication with the immune system, we discovered an endogenous repertoire of CNS-derived regulatory self-peptides presented on major histocompatibility complex (MHC) II molecules at the CNS borders. During homeostasis, these regulatory self-peptides were found to be bound to MHC II molecules throughout the path of lymphatic drainage from the brain to its surrounding meninges and its draining cervical lymph nodes. With neuroinflammatory disease, however, the presentation of regulatory self-peptides diminished. Upon boosting the presentation of these regulatory self-peptides, a population of suppressor CD4 + T cells was expanded, controlling CNS autoimmunity in a CTLA-4 and TGFβ dependent manner. This unexpected discovery of CNS-derived autoimmune self-peptides may be the molecular key adapting the CNS to maintain continuous dialogue with the immune system while balancing overt autoreactivity. This sheds new light on how we conceptually think about and therapeutically target neuroinflammatory and neurodegenerative diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

We present a method that uses viscosity-lowering materials to fabricate flexible polydimethylsiloxane-based quantum dot (QD) films with high quantum yield (QY) and improved uniformity. We found that the aggregation of individual QDs was prevented, and the QY improved simultaneously in films that contained surfactants. These films showed an improved absorption of approximately 27% in the near-UV and blue light regions, along with an improved photoluminescence of approximately 18%, indicating improved light conversion from the UV to the visible frequency region., (Creative Commons Attribution license.)

This study aimed to develop a machine learning (ML) model for predicting pulmonary embolism (PE) in patients with gastrointestinal cancers, a group at increased risk for PE. We conducted a retrospective, multicenter study analyzing patients who underwent computed tomographic pulmonary angiography (CTPA) between 2010 and 2020. The study utilized demographic and clinical data, including the Wells score and D-dimer levels, to train a random forest ML model. The model's effectiveness was assessed using the area under the receiver operating curve (AUROC). In total, 446 patients from hospital A and 139 from hospital B were included. The training set consisted of 356 patients from hospital A, with internal validation on 90 and external validation on 139 patients from hospital B. The model achieved an AUROC of 0.736 in hospital A and 0.669 in hospital B. The ML model significantly reduced the number of patients recommended for CTPA compared to the conventional diagnostic strategy (hospital A; 100.0% vs. 91.1%, P < 0.001, hospital B; 100.0% vs. 93.5%, P = 0.003). The results indicate that an ML-based prediction model can reduce unnecessary CTPA procedures in gastrointestinal cancer patients, highlighting its potential to enhance diagnostic efficiency and reduce patient burden., (© 2024. The Author(s).)

Objectives: We aim to assess the pooled incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) in clinical trials and real-world studies of chimeric antigen receptor (CAR) T-cell therapy for hematologic malignancy and compare the incidences among different agents., Methods: The PubMed, Embase, and Web of Science databases were searched for clinical trials and real-world studies. An inverse-variance weighting model was used to calculate pooled incidences and subgroup analyses. Multivariable analysis was conducted using binomial-normal modeling., Results: Seventy-five trials comprising 3,184 patients were included. The overall pooled incidence was 26.9% (95% CI, 21.7-32.7%) for all-grade and 10.5% (95% CI, 8.1-13.6%) for high-grade ICANS. In subgroup analysis, cohorts with anti-CD19 drugs had significantly higher ICANS incidences than cohorts with other agents. The multivariable analysis demonstrated higher odds of ICANS in anti-CD19 drug studies for high-grade (OR, 4.6) compared to anti-BCMA drug studies. In 12 real-world studies, studies used axicabtagene ciloleucel with CD28 (54.0% all-grade, 26.4% high-grade) exhibited significantly higher rates of all-grade and high-grade ICANS than studies using tisagenlecleucel with 4-1BB (17.2% all-grade, 6.1% high-grade)., Conclusions: The overall incidences of ICANS with CAR T-cell therapy were 26.9% for all-grade and 10.5% for high-grade. Compared with other agents, patients with anti-CD19 drugs had a significantly increased risk of developing high-grade ICANS. Therefore, careful monitoring of ICANS should be considered for patients undergoing CAR T-cell therapy., Competing Interests: RH received research support from Agios Pharmaceuticals/Bristol-Myers Squibb and consultation fees from Nuvation Bio and served on the advisory board of Vysioneer. DY received consultation fees from Abclone and GI cell and served on the advisory board of Abclone, GC cell, and GI cell. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Jeong, Suh, Park, Guenette, Huang, Kim and Yoon.)

Microplastics (MPs) pollution has recently become a major concern for agroecosystems. The interplay between MPs, and heavy metal(loid)s in the soil can intensify the risks to plant growth and human health. The current study investigated the interactive effects of arsenic (As) and biodegradable and petroleum-based conventional MPs on rice growth, As bioavailability, soil bacterial communities, and soil enzyme activities. As-contaminated soil (5 mg kg -1 ) was treated with conventional MPs i.e., polystyrene (PS) and polyethylene (PE) and biodegradable MPs i.e., polylactic acid (PLA) and polybutylene adipate terephthalate (PBAT) at 0.1 % and 1 % rates. In a pot experiment, rice plants were cultivated in soil co-contaminated with As and MPs. PLA-MPs exhibited significant interactions with As, increasing its bioavailability and impairing rice plant growth by enhancing plant oxidative stress. The results illustrated that T2 treatment (PLA-MPs @ 1 % + As 5 mg kg -1 ) significantly decreased the root and shoot lengths, root and shoot dry weights as well as the rates of photosynthesis, transpiration, intercellular CO 2 , and stomatal conductance in rice plants. Biodegradable PLA-MPs @ 1 % resulted in increased uptake of As in rice roots, stems, and leaves by 13.4 %, 38.9 %, and 20.6 %, respectively. In contrast, conventional PE-MPs @ 1 % showed contradictory results with As uptake declined by 2.2 %, 5.1 %, and 9.9 % in rice roots, stem and leaves. Soil enzyme kinetics showed that biodegradable MPs increased the activities of soil catalase, dehydrogenase, and phytase enzymes, whereas both conventional PS and PE-MPs decreased their activities. Moreover, As and PLA-MPs combined stress altered soil bacterial communities by increasing the relative abundance of Protobacteria, Acidobacteria, Chloroflexi, and Firmicutes phyla by 49 %, 29 %, 82 %, and 57 %, respectively. This study provides new insights into MPs-As interactions in soil-plant system and ecological risks associated with their coexistence., Competing Interests: Declaration of competing interest We declare that we do not have any conflicts of financial or non-financial interests, and we have all agreed to submit the article for publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: With the rising global incidence and mortality rates of breast cancer, early diagnosis is becoming increasingly crucial. The World Health Organization (WHO) recommends mammography as a primary screening tool. However, despite its clinical benefits, mammography has potential risks including radiation exposure, unnecessary follow-up, and overdiagnosis due to false positives, particularly in cases of early cancer or dense breast tissue. In this study, we aimed to address these concerns by introducing an innovative diagnostic method that employs circulating biomarkers to enhance the existing screening techniques Methods: Breast cancer-derived extracellular vesicles (BEVs) were isolated from the bloodstream using advanced immunoaffinity capture techniques. Subsequently, we analyzed the microRNA (miRNA) profiles of BEVs in plasma samples from 120 patients with breast cancer, 46 with benign tumors, and 45 healthy controls. Results: This retrospective study identified a distinct signature of five EV miRNAs (miR-21, miR-106b, miR-181a, miR-484, and miR-1260b) that effectively differentiated patients with breast cancer from healthy controls. This signature provides essential insights into tumor progression, metastasis, and the risk of recurrence. Notably, overexpression of this signature correlated with poorer survival outcomes. Conclusions: Our novel gene signature-based approach not only complements existing diagnostic methods with high accuracy but also provides a deeper understanding of the molecular aspects of breast cancer, heralding a significant advancement in precision medicine and personalized cancer care., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Human epithelial growth factor receptor 2 (HER2)-targeted therapies are effective in patients with HER2-positive breast cancer. Recent advances have shown that HER2-targeted therapies can also be of benefit when treating tumors expressing low levels of HER2, highlighting the importance of identifying the HER2-low subgroup. This clinical trend has opened new therapeutic avenues for patients who were previously ineligible for HER2-targeted therapies. Thus, the development of new diagnostic methods for real-time HER2 profiling is crucial for accurately tailoring the treatment for these patients. We hypothesized that tumor-derived extracellular vesicles (TEVs) could reflect the HER2 profiles of primary tumors and potentially serve as diagnostic tools for HER2 status. This approach was validated using six breast cancer cell lines, which confirmed that the TEVs accurately reflected the HER2 profiles of the tumor cells. TEVs were isolated using an immunoaffinity method, and copy number variation (CNV) in the ERBB2/EIF2C ratio was assessed using droplet digital PCR of DNA from these vesicles. Clinical validation using plasma samples from 33 breast cancer patients further reinforced the diagnostic potential of our method. Pearson's correlation coefficient analysis of the flow cytometry results demonstrated that TEVs reflected HER2 expression in primary cells. To distinguish between HER2-negative and HER2-low patients, the area under the curve (AUC) of the ROC curve in our method was 0.796, with a sensitivity of 53.8% and a specificity of 100%. These findings suggest the clinical utility of extracellular vesicles derived from plasma and emphasize the need for further research to distinguish HER2-negative from HER2-low patients., (© 2024 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)

Traumatic injuries to the central nervous system (CNS) afflict millions of individuals worldwide 1 , yet an effective treatment remains elusive. Following such injuries, the site is populated by a multitude of peripheral immune cells, including T cells, but a comprehensive understanding of the roles and antigen specificity of these endogenous T cells at the injury site has been lacking. This gap has impeded the development of immune-mediated cellular therapies for CNS injuries. Here, using single-cell RNA sequencing, we demonstrated the clonal expansion of mouse and human spinal cord injury-associated T cells and identified that CD4 + T cell clones in mice exhibit antigen specificity towards self-peptides of myelin and neuronal proteins. Leveraging mRNA-based T cell receptor (TCR) reconstitution, a strategy aimed to minimize potential adverse effects from prolonged activation of self-reactive T cells, we generated engineered transiently autoimmune T cells. These cells demonstrated notable neuroprotective efficacy in CNS injury models, in part by modulating myeloid cells via IFNγ. Our findings elucidate mechanistic insight underlying the neuroprotective function of injury-responsive T cells and pave the way for the future development of T cell therapies for CNS injuries., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: To identify damage to the inner retinal layer and microvasculature in the peripapillary area according to the severity of diabetic retinopathy (DR)., Methods: Patients were divided into four groups: control (group 1), type 2 diabetes (T2DM) without DR (group 2), mild to moderate nonproliferative DR (NPDR) (group 3), and severe NPDR (group 4). The peripapillary retinal nerve fiber layer (pRNFL) thickness and peripapillary vessel density (VD) were compared. Linear regression analysis was performed to identify factors associated with the DR severity., Results: The average pRNFL thicknesses were 96.2 ± 7.1, 94.1 ± 9.6, 92.0 ± 9.9, and 90.3 ± 12.4 μm in groups 1, 2, 3, and 4, respectively (P = 0.003) (post hoc analyses: group 1 vs. group 2, P = 0.529; group 2 vs. group 3, P = 0.627; group 2 vs. group 4, P = 0.172; group 3 vs. group 4, P = 0.823). The VDs of the outer ring were 18.9 ± 0.6, 18.4 ± 0.8, 17.9 ± 1.1, and 17.3 ± 1.6 mm -1 in groups 1, 2, 3 and 4, respectively (P < 0.001) (all pairwise comparisons, P < 0.050). In multivariate analysis, the VD of the outer ring (B = - 0.35, P < 0.001) was significantly associated with the DR severity., Conclusions: The peripapillary microvasculature reflects retinal damage following DR progression better than the structure of the pRNFL., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Background: We aimed to identify the prognostic factors for late intrahepatic recurrence (IHR), defined as recurrence more than two years after curative treatment of newly diagnosed hepatocellular carcinoma (HCC)., Methods: This retrospective cohort study included patients with newly diagnosed, previously untreated, very early, or early HCC treated with initial curative treatment and followed up without recurrence for more than two years, excluding early IHR defined as recurrence within two years in single center. Late IHR-free survival (IHRFS) was defined as the time interval from initial curative treatment to the first IHR or death without IHR, whichever occurred first., Results: Among all the enrolled 2,304 patients, 1,427 (61.9%) underwent curative intent hepatectomy and the remaining 877 (38.1%) underwent local ablative therapy (LAT). During the follow-up after curative treatment (median, 82.6 months; range, 24.1 to 195.7), late IHR was detected in 816 (35.4%) patients. In the multivariable analysis, age, male sex, cirrhotic liver at diagnosis, type of initial treatment, and modified albumin-bilirubin (mALBI) grade were significant prognostic baseline factors. Furthermore, mALBI grade at three (2a vs. 1, P = 0.02, hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.04-1.70; 2b/3 vs. 1, P = 0.03; HR, 1.42; 95% CI, 1.03-1.94) and six months (2b/3 vs. 1; P = 0.006; HR, 1.61; 95% CI, 1.13-2.30) after initial curative treatment was also a significant prognostic factor for late IHR., Conclusion: After curative treatment for newly diagnosed early HCC, the mALBI grade at three and six months after initial curative treatment, as well as at baseline, was one of the most crucial prognostic factors for late IHR., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Introduction: We aimed to describe patient awareness regarding fall prevention and education, perceived causes of falls, and changes in attitude after experiencing a fall through interviews with older Korean patients who experienced falls with resultant hip fractures., Materials and Methods: We conducted face-to-face semi-structured in-depth interviews with 11 patients who were admitted to Kangbuk Samsung Hospital for hip fractures caused by falls and were referred to the Department of Rehabilitation Medicine for postsurgical rehabilitation between June 2022 and June 2023. The data were analyzed using the phenomenological method developed by Colaizzi., Results: Before hip fracture, none of the patients had received fall prevention education or perceived its necessity; however, they recognized its necessity retrospectively. Participants described the causes of falls as carelessness, actions taken at the time of the fall, environmental factors, and decreased physical function. Most participants believed that falls could be prevented through personal caution and activity restrictions. Some mentioned fall prevention education, exercise, wearing appropriate shoes, environmental adjustments, and seeking assistance from others as methods of preventing future falls. Most patients reported adopting a safety-seeking attitude after experiencing hip fracture. Many patients had negative thoughts such as guilt or thoughts of death, whereas only a few reported increased interest in education and exercise., Conclusions: We observed a lack of fall prevention education, misunderstanding regarding the cause of falls, and negative psychological changes after experiencing hip fractures due to falls in older Korean individuals. Recognizing and managing patient perceptions is crucial for effective fall prevention, requiring both healthcare provider awareness and active participation from patients and caregivers., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

While there have been notable advancements in Si-based optical integration, achieving compact and efficient continuous-wave (CW) III-V semiconductor nanolasers on Si at room temperature remains a substantial challenge. This study presents an innovative approach: the on-demand minimal-gain-printed Si nanolaser. By using a carefully designed minimal III-V optical gain structure and a precise on-demand gain-printing technique, we achieve lasing operation with superior spectral stability under pulsed conditions and observe a strong signature of CW operation at room temperature. These achievements are attributed to addressing both fundamental and technological issues, including carrier diffusion, absorption loss, and inefficient thermal dissipation, through minimal-gain printing in the nanolaser. Moreover, our demonstration of the laser-on-waveguide structure emphasizes the integration benefits of this on-demand gain-printed Si nanolaser, highlighting its potential significance in the fields of Si photonics and photonic integrated circuits.

The management of metastatic hormone-sensitive prostate cancer (mHSPC) or castration-sensitive prostate cancer (mCSPC) has become increasingly complex with the tremendous progress that has been made in this space within the past few decades. In the early days of androgen deprivation therapy (ADT), ADT monotherapy was the mainstay for treatment of advanced prostate cancer. However, novel hormone therapies in the form of androgen receptor pathway inhibitors (ARPI) have emerged; vaccine therapy, chemotherapy with docetaxel and cabazitaxel, and radioactive ligands have shaped the treatment of metastatic prostate cancer in the last decade. Following the initial approval of several drugs for use in metastatic castration-resistant prostate cancer (mCRPC) in combination with primary ADT, these agents were studied and subsequently approved for use in mCSPC. Therefore, ADT monotherapy no longer constitutes an optimal therapeutic option for otherwise fit patients who present with mCSPC. We focus on the treatment of first-line de novo mHSPC or mCSPC and explore frontline doublet and triplet therapy and the pivotal trials that led to their United States Food and Drug Administration approval., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JBA-C serves in the Speakers’ Bureau of BMS and Astellas/Pfizer/Seattle Genetics and serves in the Advisory Board of Pfizer/EMD Serono, Merck and AstraZeneca and Immunomedics, Janssen, Pfizer/Astellas, Seagen, Dendreon, Bayer. E-MY, MWH, IP, and FP have no conflicts to declare., (© The Author(s) 2024.)

Background: Amelanotic acral melanoma (AAM) is a rare type of acral melanoma that has a poor prognosis., Objectives: To investigate the transcriptomic differences between AAM and pigmented acral melanoma (PAM)., Methods: Differences in the spatially resolved transcriptomic profiles of 9 patients with AAM with 29 regions of interest (ROIs) and 11 patients with PAM with 46 ROIs were investigated using S100b and CD3 morphology markers., Results: In S100b+ tumour cell areas, we detected 11 upregulated differentially expressed genes (DEGs; including chaperone/ubiquitin--associated DEGs) and 82 downregulated DEGs (including human leucocyte antigen) in AAMs vs. PAMs. Protein-protein interaction network and pathway analyses revealed significant enrichment of dysregulated translational and nonsense-mediated decay pathways but significant decreases in antigen processing and presentation, interferon signalling and melanin biosynthesis pathways in S100b+ ROIs of AAMs compared with PAMs. In tumour-associated immune cell areas, the numbers of CD8 T cells (P = 0.04) and M1 macrophages (P = 0.01) were significantly decreased, whereas those of monocytes (P = 0.04) and endothelial cells (P = 0.04) were increased in AAMs compared with PAMs., Conclusions: These findings could widen our understanding of the biological differences between AAMs and PAMs, which might result in a different clinical course., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Human adenovirus (HAdV) is a prevalent causative agent of acute respiratory disease (ARD) and is frequently responsible for outbreaks, particularly in military environments. Current vaccines do not effectively cover HAdV subtypes commonly found among Korean military personnel, highlighting the need for a new targeted vaccine. This study presents a cost-benefit analysis to evaluate the economic viability of developing and implementing such a vaccine within a military context., Methods: We adopted a societal perspective for this cost-benefit analysis, which included estimating costs associated with vaccine development, production, and distribution over a projected timeline. We assumed a development period of five years, after which vaccine production and administration were initiated in the sixth year. The cost associated with vaccine development, production, and dispensation was considered. The benefits were calculated based on both direct and indirect cost savings from preventing HAdV infections through vaccination. All financial figures were expressed in 2023 US dollars. A sensitivity analysis was conducted to explore the impact of varying factors such as vaccination rate, incidence of infection, vaccine efficacy, and discount rate., Results: For the base case scenario, we assumed a vaccination rate of 100 %, an incidence rate of 0.02, and a vaccine efficacy of 95 %, applying a 3 % discount rate. Initially, in the sixth year, the benefit-cost ratio stood at 0.71, suggesting a cost disadvantage at the onset of vaccination. However, this ratio improved to 1.32 in the following years, indicating a cost benefit from the seventh year onward. The cumulative benefit-cost ratio over a decade reached 2.72. The outcomes from the sensitivity analysis were consistent with these findings., Conclusion: Our cost-benefit analysis demonstrates that the introduction of an HAdV vaccine for the Korean military is economically advantageous, with substantial cost benefits accruing from the seventh year after the commencement of vaccination., 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: Ectodermal dysplasia (ED) is a rare genetic disorder that affects structures derived from the ectodermal germ layer., Results: In this study, we analyzed the genetic profiles of 27 Korean patients with ED. Whole exome sequencing (WES) was performed on 23 patients, and targeted panel sequencing was conducted on the remaining 4 patients. Among the patients in the cohort, 74.1% (20/27) tested positive for ED. Of these positive cases, EDA and EDAR mutations were found in 80% (16/20). Notably, 23.1% (3/13) of EDA-positive cases exhibited copy number variations. Among the 23 patients who underwent WES, we conducted a virtual panel analysis of eight well-known genes, resulting in diagnoses for 56.5% (13/23) of the cases. Additionally, further analysis of approximately 5,000 OMIM genes identified four more cases, increasing the overall positivity rate by approximately 17%. These findings underscore the potential of WES for improving the diagnostic yield of ED. Remarkably, 94.1% of the patients manifesting the complete triad of ED symptoms (hair/skin/dental) displayed detectable EDA/EDAR mutations. In contrast, none of the 7 patients without these three symptoms exhibited EDA/EDAR mutations., Conclusions: When conducting molecular diagnostics for ED, opting for targeted sequencing of EDA/EDAR mutations is advisable for cases with classical symptoms, while WES is deemed an effective strategy for cases in which these symptoms are absent., (© 2024. The Author(s).)

Prime editing (PE) is a recently developed genome-editing technique that enables versatile editing. Despite its flexibility and potential, applying PE in human induced pluripotent stem cells (hiPSCs) has not been extensively addressed. Genetic disease models using patient-derived hiPSCs have been used to study mechanisms and drug efficacy. However, genetic differences between patient and control cells have been attributed to the inaccuracy of the disease model, highlighting the significance of isogenic hiPSC models. Hereditary hemorrhagic telangiectasia 1 (HHT1) is a genetic disorder caused by an autosomal dominant mutation in endoglin ( ENG ). Although previous HHT models using mice and HUVEC have been used, these models did not sufficiently elucidate the relationship between the genotype and disease phenotype in HHT, demanding more clinically relevant models that reflect human genetics. Therefore, in this study, we used PE to propose a method for establishing an isogenic hiPSC line. Clinically reported target mutation in ENG was selected, and a strategy for PE was designed. After cloning the ENG ineered PE guide RNA, hiPSCs were nucleofected along with PEmax and hMLH1dn plasmids. As a result, hiPSC clones with the intended mutation were obtained, which showed no changes in pluripotency or genetic integrity. Furthermore, introducing the ENG mutation increased the expression of proangiogenic markers during endothelial organoid differentiation. Consequently, our results suggest the potential of PE as a toolkit for establishing isogenic lines, enabling disease modeling based on hiPSC-derived disease-related cells or organoids. This approach is expected to stimulate mechanistic and therapeutic studies on genetic diseases.a.

Purpose: To evaluate the efficacy and toxicities of skin-directed radiotherapy (RT) in primary cutaneous T-cell lymphoma (CTCL)., Materials and Methods: We retrospectively analyzed 57 CTCL lesions treated with skin-directed RT between January 2000 and December 2022. Lesions were categorized into three distinct groups: early-stage disease treated with local RT, advanced-stage disease treated with local RT, and advanced-stage disease treated with total skin electron beam therapy (TSEBT). Treatment outcomes, including response rates, recurrence patterns, and local progression probability, were assessed for each group., Results: Mycosis fungoides (MF) constituted 90.9% of the advanced-stage pathologies, while CD4+ primary cutaneous small/medium T-cell lymphoproliferative disorder was common in the early stage lesions (55%). Median RT doses were 30.6 Gy, 27 Gy, and 32 Gy for the local RT with early stage, the local RT with advanced stage, and TSEBT with advanced stage, respectively. The complete response rates were high across the groups: 95.5%, 70.8%, and 90.9%, respectively. Seven local recurrences (29.2%) occurred in the local RT group with advanced stage, while seven patients (63.6%) in the TSEBT group experienced local failure. All recurrences were observed in lesions and patients with MF. Acute toxicities were mainly grade 1 or 2, with no grade 3 or higher events. No significant association between RT dose and local progression rates in MF lesions was found., Conclusion: Skin-directed RT in CTCL is effective for local control and well-tolerated with less toxicity.

Objective: To determine the preventive effect of changing gadolinium-based contrast agents (GBCAs) to reduce the recurrence of GBCA-associated acute adverse drug reactions (ADRs)., Materials and Methods: This retrospective, observational, single-center study-conducted between January 2016 and December 2021-included 238743 consecutive GBCA-enhanced MRI examinations. We focused on a subgroup of patients who experienced acute GBCA-associated ADRs during any of these examinations and subsequently underwent follow-up GBCA-enhanced MRI examinations up until July 2023. The follow-up examinations involved either the same (non-change group) or different (change group) GBCAs compared to the ones that initially caused the acute ADR. Baseline participant characteristics, generic profile of the GBCAs, administration of premedication, history of prior ADR to iodinated contrast media, and symptoms of GBCA-associated acute ADRs were retrospectively analyzed. Multivariable logistic regression with generalized estimating equations and propensity score matching were used., Results: A total of 1042 instances of acute ADRs (0.44%; 95% confidence interval [CI]: 0.41%-0.46%) were reported. Three-hundred and seventy-three patients underwent GBCA-enhanced MRI examinations after experiencing GBCA-associated acute ADRs within the study period; 31.9% (119/373) reexperienced acute ADRs at any of the follow-up examinations. The ADR recurrence was significantly lower in the GBCA change group than in the non-change group according to multivariable logistic regression (adjusted odds ratio [OR]: 0.35; 95% CI: 0.13-0.90; P = 0.03) and analysis with propensity score matching (14.3% [6/42] vs. 36.9% [31/84], respectively; OR: 0.32, 95% CI: 0.11-0.94; P = 0.04). A history of an ADR to iodinated contrast media (OR: 1.14, 95% CI: 0.68-1.90; P = 0.62) and premedication (adjusted OR: 2.09, 95% CI: 0.93-4.68; P = 0.07) were not significantly associated with GBCA-associated acute ADR recurrence. A separate analysis for recurrent allergic-like hypersensitivity reactions demonstrated similar results (adjusted OR: 0.20, 95% CI: 0.06-0.65; P < 0.01)., Conclusion: Changing GBCAs may reduce the risk of GBCA-associated acute ADR recurrence., Competing Interests: Chong Hyun Suh, who holds respective positions on the Assistant to the Editor of the Korean Journal of Radiology, was not involved in the editorial evaluation or decision to publish this article. The remaining author has declared no conflicts of interest., (Copyright © 2024 The Korean Society of Radiology.)

It is self-evident that our chests expand and contract during breathing but, surprisingly, exactly how individual alveoli change shape over the respiratory cycle is still a matter of debate. Some argue that all the alveoli expand and contract rhythmically. Others claim that the lung volume change is due to groups of alveoli collapsing and reopening during ventilation. Although this question might seem to be an insignificant detail for healthy individuals, it might be a matter of life and death for patients with compromised lungs. Past analyses were based on static post-mortem preparations primarily due to technological limitations, and therefore, by definition, incapable of providing dynamic information. In contrast, this study provides the first comprehensive dynamic data on how the shape of the alveoli changes, and, further, provides valuable insights into the optimal lung volume for efficient gas exchange. It is concluded that alveolar micro-dynamics is nonlinear; and at medium lung volume, alveoli expand more than the ducts., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)