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Sunghwa You, 1, 2 Woojae Han, 1–3 Saea Kim, 1, 2 Sanga Maeng, 4 Young Joon Seo 4 1Laboratory of Hearing and Technology; 2Division of Speech Pathology and Audiology; 3Research Institute of Audiology and Speech Pathology, College of Natural Sciences, Hallym University, Chuncheon, Korea; 4Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, Wonju, KoreaCorrespondence: Woojae Han #8603 Natural Sciences Bd., 1 Hallymdaehak-Gil, Chuncheon 24252, Republic of KoreaTel +82-33-248-2216Fax +82-33-256-3420Email woojaehan@hallym.ac.krObjective: The present study aimed to identify the reliability and validity of a screening tool for the elderly who wish to check their level of hearing loss by themselves.Design: A total of 170 older adults with different hearing levels participated. The Self-Assessment for Hearing Screening of the Elderly-Revised (SHSE-R) consisted of 20 questions measured on a 5-point scale and developed in terms of characteristics of age-related hearing loss. For reliability, the subjects responded to SHSE-R twice with a three-week interval. They also took various subjective and objective hearing tests and a working memory test and filled out two other questionnaires for validation.Results: SHSE-R showed a high internal consistency and a high reliability when comparing test–retest scores. Its content validity was as high as 0.88– 1. Convergent validity supported SHSE-R and its subcategories while showing either a positive or negative correlation with pure-tone average, word recognition scores, and otoacoustic emission tests. Construct validity was proved by a moderate negative correlation with the tests of speech in noise, speech with fast speed, and working memory. In criterion validity, a strong positive correlation existed between SHSE-R and the other questionnaires, except for a group with severe hearing loss. The factor analysis showed similar results to the original version of SHSE having three factors, although some items were interchanged.Conclusion: We confirmed that SHSE-R was well developed with both excellent internal consistency and test–retest reliability and valuable convergent, construct, and criterion validities, consequently making SHSE-R useful for self-checking hearing loss in the elderly.Keywords: hearing screening, self-assessment, questionnaire, age-related hearing loss, older adults

Ye Ji Ahn1,2 Tae Hoon Kong1,2 Jin Sil Choi1,2 Wan Su Yun,3 Jaehong Key,3 Young Joon Seo1,21Research Institute of Hearing Enhancement, Yonsei University Wonju College of Medicine, Wonju, South Korea; 2Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, Wonju, South Korea; 3Department of Biomedical Engineering, Yonsei University, Wonju, South KoreaAbstract: Stem cells possess a promising potential in the clinical field. The application and effective delivery of stem cells to the desired target organ or site of injury plays an important role. This review describes strategies on understanding the effective delivery of stem cells labeled with superparamagnetic iron oxide nanoparticles (SPION) using an external magnet to enhance stem cell migration in vivo and in vitro. Fourteen total publications among 174 articles were selected. Stem cell type, SPION characteristics, labeling time, and magnetic force in vivo are considered important factors affecting the effective delivery of stem cells to the homing site. Most papers reported that the efficiency was increased when magnet is applied compared to those without. Ten studies analyzed the homing competency of SPION-labeled MSCs in vitro by observing the migration of the cell toward the external magnet. In cell-based experiments, the mechanism of magnetic attraction, the kind of nanoparticles, and various stem cells were studied well. Meta-analysis has shown the mean size of nanoparticles and degree of recovery or regeneration of damaged target organs upon in vivo studies. This strategy may provide a guideline for designing studies involving stem cell homing and further expand stem cell.Keywords: stem cells, homing, SPION, magnetic attraction, stem cell therapy, systematic review

Background: It is important to differentiate sinonasal fungus ball from non-fungal sinusitis and other forms of fungal sinusitis in order to determine the optimal treatment. In particular, a sinonasal fungus ball, a non-invasive fungal sinusitis, can be characterized by radiologic findings before surgery. Purpose: To differentiate a sinonasal fungus ball from other types of sinusitis and determine optimal treatment on the basis of radiologic findings before surgery. Material and Methods: We studied 119 patients with clinically and pathologically proven sinonasal fungus balls. Their condition was evaluated radiologically with contrast-enhanced CT (99 patients), non-contrast CT (18 patients) and/or MRI (17 patients) prior to sinonasal surgery. Results: Calcifications were found in 78 of 116 (67.2%) patients who underwent CT scans for fungus ball. As opposed to non-contrast CT scans, contrast CT scans revealed hyperattenuating fungal ball in 82.8% and enhanced inflamed mucosa in 65.5% of the patients, respectively. On MRI, most sinonasal fungal balls showed iso- or hypointensity on T1-weighted images and marked hypointensity on T2-weighted images. Inflamed mucosal membranes were noted and appeared as hypointense on T1-weighted images (64.7%) and hyperintense on T2-weighted images (88.2%). Conclusion: When there are no calcifications visible on the CT scan, a hyperattenuating fungal ball located in the central area of the sinus with mucosal thickening on enhanced CT scans is an important feature of a non-invasive sinonasal fungus ball. On MRI, a sinonasal fungus ball has typical features of a marked hypointense fungus ball with a hyperintense mucosal membrane in T2-weighted images. A contrast-enhanced CT scan or MRI provides sufficient information for the preoperative differentiation of a sinonasal fungus ball from other forms of sinusitis. [ABSTRACT FROM AUTHOR]

Epithelial cell adhesion molecule (EpCAM) fused to IgG, IgA and IgM Fc domains was expressed to create IgG, IgA and IgM-like structures as anti-cancer vaccines in Nicotiana tabacum. High-mannose glycan structures were generated by adding a C-terminal endoplasmic reticulum (ER) retention motif (KDEL) to the Fc domain (FcK) to produce EpCAM-Fc and EpCAM-FcK proteins in transgenic plants via Agrobacterium-mediated transformation. Cross-fertilization of EpCAM-Fc (FcK) transgenic plants with Joining chain (J-chain, J and JK) transgenic plants led to stable expression of large quaternary EpCAM-IgA Fc (EpCAM-A) and IgM-like (EpCAM-M) proteins. Immunoblotting, SDS-PAGE and ELISA analyses demonstrated that proteins with KDEL had higher expression levels and binding activity to anti-EpCAM IgGs. IgM showed the strongest binding among the fusion proteins, followed by IgA and IgG. Sera from BALB/c mice immunized with these vaccines produced anti-EpCAM IgGs. Flow cytometry indicated that the EpCAM-Fc fusion proteins significantly activated CD8 + cytotoxic T cells, CD4 + helper T cells and B cells, particularly with EpCAM-FcK P and EpCAM-Fc P (FcK P ) × J P (JK P ). The induced anti-EpCAM IgGs captured human prostate cancer PC-3 and colorectal cancer SW620 cells. Sera from immunized mice inhibited cancer cell proliferation, migration and invasion; down-regulated proliferation markers (PCNA, Ki-67) and epithelial-mesenchymal transition markers (Vimentin); and up-regulated E-cadherin. These findings suggest that N. tabacum can produce effective vaccine candidates to induce anti-cancer immune responses., (© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Background / Objective : The rise in sports participation among children and adolescents has led to an increase in ACL injuries in skeletally immature individuals. This study analyzed nationwide trends in the anterior cruciate ligament (ACL) reconstruction surgeries in pediatric and adolescent populations, addressing concerns about growth plate disturbances with surgery and risks of secondary injuries with nonoperative treatment. Methods : We conducted a retrospective population-based cohort study using the National Health Insurance Corporation database in South Korea, analyzing ACL reconstruction trends from 2011 to 2018. Patients were categorized into four age groups (≤12 years, 13-15 years, 16-17 years, and ≥18 years). The Chi-square linear-by-linear association test was used to analyze trends in procedural volumes, age groups, and regions. Poisson regression was used to examine whether differences over time were statistically significant by modeling count data and estimating incidence rate ratios (IRRs) with 95% confidence intervals (CIs). It also evaluates the statistical differences by age, gender, and hospital location. Results : A total of 83,132 patients underwent ACL reconstruction during the study period. The ≤12-year-old group accounted for a stable, low percentage of surgeries (16.6% in 2011 to 23.7% in 2018) with no significant trends observed (IRR = 0.99, p = 0.683). Conversely, significant increases were noted in patients aged 13-15 years (IRR = 1.04, p < 0.001), 16-17 years (IRR = 1.03, p < 0.001), and aged ≥18 years (IRR = 1.03, p < 0.001). Male patients and urban hospital locations were associated with higher surgical rates. Conclusions : During the study period, ACL reconstruction is rare in children ≤12 years old due to concerns about growth disturbances, while adolescents 13-17 years old show increased surgical rates due to evolving practices supporting early intervention. These findings emphasize the need for individualized treatment balancing early benefits and growth plate risks.

Objectives: Although obesity is typically correlated with adverse outcomes in various diseases, certain acute critical illnesses exhibit a phenomenon known as the obesity paradox. This study evaluated sex-specific differences in the prognostic implications of the body mass index (BMI) of patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT)., Design: A multicenter retrospective cohort study., Setting: Data from eight tertiary hospitals in Korea., Patients: A total of 3805 critically ill patients receiving CRRT. Patients were categorized into four BMI groups: underweight, normal weight, overweight, and obese., Interventions: None., Measurements and Main Results: There were 2308 male and 1497 female patients. The 90-day mortality risk significantly differed among BMI groups in the overall patient population and the male subpopulation but not the female subpopulation. Following adjustment for confounding variables, the 90-day mortality risk was higher in the underweight group than in the obese group (hazard ratio [HR], 1.20; 95% CI, 1.05-1.36; p = 0.006). Among male patients, the 90-day mortality risk was higher in both the underweight and normal weight groups than in the obese group (underweight: HR, 1.30; 95% CI, 1.10-1.53; p = 0.002 and normal weight: HR, 1.18; 95% CI, 1.04-1.35; p = 0.010); however, no such association was observed among female patients. Subgroup analysis demonstrated the obesity paradox in male patients of old age, with septic AKI, or with low albumin levels., Conclusions: There were sex differences in the association between BMI and mortality in critically ill patients with severe AKI. Although the precise distribution of fat mass and muscle mass was not identified, obese male patients had a more favorable prognosis, which was not evident among female patients. These findings highlight the importance of considering sex-specific factors in understanding the complex relationship between obesity and mortality in critically ill patients with AKI., Competing Interests: The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

By employing Data Envelopment Analysis (DEA) with Slacks-Based Measure (SBM) and DEA-Undesirable Output models, this study aims to investigate the operational and environmental efficiency of 26 major ports across China's Special Economic Zones (SEZs). Focusing on the interplay between operation performance and environmental sustainability, this research evaluates how well these ports manage their operational activities while minimizing their environmental impact. The results indicate that the ports in the Yangtze River Delta, Pearl River Delta, and Southwest Coast significantly outperform others. These ports benefit from advanced infrastructural setups and operational capabilities that enhance throughput while adhering to environmental standards. This study underscores the importance of integrating sustainable practices and green technologies into port operations, suggesting that such integration not only reduces ecological footprints but also bolsters efficiency. It highlights areas where ports lag in efficiency and proposes targeted interventions to enhance environmental and operational outcomes. By identifying the correlation between high efficiency scores and low CO2 emissions, this paper presents a compelling argument for adopting more stringent environmental measures in port management practices, thereby aligning port operations with global sustainability goals., 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.)

The sphingolipid network is sustained principally by the balance of bioactive sphingolipid molecules and their regulation by sphingolipid-metabolizing enzymes. The components in the lipid system display key functions in numerous cellular and disease conditions including virus infections. During the COVID-19 pandemic, there was a fruitful effort to use an inhibitor that blocks the activity of sphingosine kinase (SphK) 2 to cure the devastating disease. Support for the inhibitor came from pre-clinical research on influenza where the inhibitor demonstrated effective protection of mice from influenza-induced morbidity and mortality. This highlights the importance of basic and translational research on the sphingolipid system for improving human health. Multiple sphingolipid-metabolizing enzymes have been reported to regulate influenza virus replication and propagation. In this review, the emphasis is placed on the roles of these enzymes that impact influenza virus life cycle and the conceivable mechanisms for the interplay between influenza virus and the sphingolipid pathway., 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 Inc. All rights reserved.)

Background: In 2006, the Korean Atopic Dermatitis Association (KADA) working group released the diagnostic criteria for Korean atopic dermatitis (AD). Recently, more simplified, and practical AD diagnostic criteria have been proposed., Objective: Based on updated criteria and experience, we studied to develop and share a consensus on diagnostic criteria for AD in Koreans., Materials and Methods: For the diagnostic criteria, a questionnaire was constructed by searching the English-language literature in MEDLINE and the Cochrane Database of Systematic Reviews. A modified Delphi method composed of 3 rounds of email questionnaires was adopted for the consensus process. Fifty-four KADA council members participated in the 3 rounds of votes and expert consensus recommendations were established., Results: Diagnostic criteria for AD include pruritus, eczema with age-specific pattern, and chronic or relapsing history. Diagnostic aids for AD encompass xerosis, immunoglobulin E reactivity, hand-foot eczema, periorbital changes, periauricular changes, perioral changes, nipple eczema, perifollicular accentuation, and personal or family history of atopy., Conclusion: This study streamlined and updated the diagnostic criteria for AD in Korea, making them more practicable for use in real-world clinical field., Competing Interests: The authors have nothing to disclose., (© 2025 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Introduction: Conventional vestibular rehabilitation therapy (VRT) requires significant time and resources, especially for patients with low compliance, limiting its effectiveness and accurate assessment. Studies have shown VRT using virtual reality (VR) to be effective, with meta-analyses confirming its superiority over conventional methods. However, methodological variations in VR remain a limitation. This study aimed to assess the effects of VRT using head-mounted display (HMD) VR technology in patients with acute unilateral vestibulopathy (AUVP) and compare the outcomes with conventional VRT., Methods: We conducted a single-blinded randomized controlled trial with 60 AUVP patients randomly assigned to VR or control groups. The VR group received VRT via VR, while the control group underwent conventional VRT. Both groups followed individual home-based programs for 8 weeks and visited the clinic every 2 weeks. Subjective dizziness symptoms were evaluated using the visual analog scale (VAS), dizziness handicap inventory (DHI), and Activities-specific Balance Confidence (ABC) scale. Compliance with home-based programs was assessed on a 0-2-point scale based on responses in a booklet guide., Results: Seven patients were lost to follow-up, leaving 26 and 27 patients in the VR and control groups, respectively. The mean patient age was 56.91 ± 12.11 years; 22 men and 33 women were included. Two-way repeated measures analysis of variance showed significant improvement in both groups for DHI and ABC scores. However, changes in DHI, VAS, and compliance scores did not differ between groups. Improvement in the physical domain of the DHI and ABC scores was significantly faster in the VR group ( p  = 0.019 for DHI, p  = 0.0020 for ABC)., Discussion: VRT using VR technology showed comparable efficacy to conventional VRT in AUVP patients. The VR group demonstrated greater improvement in the physical domain of the DHI and ABC scales, indicating enhanced confidence in movement and reduced perception of physical handicap due to dizziness., Competing Interests: The 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 © 2025 Lee, Yoon, Kim, Seo and Kong.)

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the global swine industry due to its high genetic diversity and different virulence levels, which complicate disease management and vaccine development. This study evaluated longitudinal changes in the immune cell composition of bronchoalveolar lavage fluid and the clinical outcomes across PRRSV strains with varying virulence, using techniques including single-cell transcriptomics. In highly virulent infection, faster viral replication results in an earlier peak lung-damage time point, marked by significant interstitial pneumonia, a significant decrease in macrophages, and an influx of lymphocytes. Viral tracking reveals less than 5% of macrophages are directly infected, and further analysis indicates bystander cell death, likely regulated by exosomal microRNAs as a significant factor. In contrast, the peak intermediate infection shows a delayed lung-damage time point with fewer cell population modifications. Furthermore, anti-inflammatory M2-like macrophages (SPP1-CXCL14 high ) are identified and their counts increase during the peak lung-damage time point, likely contributing to local defense and lung recovery, which is not observed in high virulent infection. These findings provide a comprehensive description of the immune cellular landscape and differential PRRSV virulence mechanisms, which will help build new hypotheses to understand PRRSV pathogenesis and other respiratory infections., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Human mesenchymal stromal cells (MSCs) possess regenerative potential due to pluripotency and paracrine functions. However, their stemness and immunomodulatory capabilities are sub-optimal in conventional two-dimensional (2D) culture., Aim: To enhance the efficiency and therapeutic efficacy of MSCs, an in vivo -like 3D culture condition was applied., Methods: MSCs were cultured on polystyrene (2D) or in a gellan gum-based 3D system. In vitro , prostaglandin-endoperoxide synthase 2, indoleamine-2,3-dioxygenase, heme oxygenase 1, and prostaglandin E synthase gene expression was quantified by quantitative real-time polymerase chain reaction. MSCs were incubated with lipopolysaccharide (LPS)-treated mouse splenocytes, and prostaglandin E2 and tumor necrosis factor-alpha levels were measured by enzyme linked immunosorbent assay. In vivo , LPS was injected into the lateral ventricle of mouse brain, and MSCs were administered intravenously the next day. Animals were sacrificed and analyzed on days 2 and 6., Results: Gellan gum polymer-based 3D culture significantly increased expression of octamer-binding transcription factor 4 and Nanog homeobox stemness markers in human MSCs compared to 2D culture. This 3D environment also heightened expression of cyclooxygenase-2 and heme-oxygenase 1, enzymes known for immunomodulatory functions, including production of prostaglandins and heme degradation, respectively. MSCs in 3D culture secreted more prostaglandin E2 and effectively suppressed tumor necrosis factor-alpha release from LPS-stimulated splenocytes and surpassed the efficiency of MSCs cultured in 2D. In a murine neuroinflammation model, intravenous injection of 3D-cultured MSCs significantly reduced ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein expression, mitigating chronic inflammation more effectively than 2D-cultured MSCs., Conclusion: The microenvironment established in 3D culture serves as an in vivo mimetic, enhancing the immunomodulatory function of MSCs. This suggests that engineered MSCs hold significant promise a potent tool for cell therapy., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Neck ultrasound (US) and serum thyroglobulin (Tg) measurements are mainstays of long-term differentiated thyroid cancer (DTC) surveillance. Given the high sensitivity of serum Tg, we aimed to assess the utility of neck US in DTC patients who underwent total thyroidectomy and have undetectable serum Tg., Methods: We performed a retrospective cohort analysis of DTC patients who underwent a total thyroidectomy at our institution (2010-2023) and received US-guided fine needle aspiration (FNA) during their surveillance. Patients were categorised into three lab categories based on serum Tg and Tg antibody (Tg Ab) status before the biopsy: (1) 'Negative Tg' if undetectable Tg ( < 0.2 ng/dL) and Tg Ab, (2) 'Positive Tg' if detectable Tg and undetectable Tg Ab, and (3) 'Positive Tg Ab' if detectable Tg Ab. To calculate the positive predictive value (PPV) of neck US, we defined the 'true positive' of US as findings that prompted an FNA biopsy resulting with DTC, and 'false positive' findings prompting an FNA biopsy that did not result as DTC., Results: A total of 118 patients were included, encompassing 146 FNA biopsies: 33 (23%) had Negative Tg, 84 (57%) had Positive Tg, and 29 (20%) had Positive Tg Ab lab results before their biopsies. The PPV of neck US in the setting of Negative Tg was 3% (one true positive, 32 false positives), while the PPV was 50% (42 true positives, 42 false positives) for Positive Tg, and 52% (15 true positives, 14 false positives) for Positive Tg Ab cohorts. Sub-analysis of the Positive Tg cohort using different serum Tg level cutoffs revealed a PPV of 29% at just detectable serum Tg of 0.2 ng/dL, and PPV of 38% for Tg < 1.0 ng/dL. The PPV stabilised at 58% for Tg levels ≥ 1 ng/dL., Conclusion: With the low PPV of neck US, high cost of surveillance, and the advent of ultra-sensitive serum Tg measurements, future guidelines should consider reducing routine neck US surveillance in patients with undetectable serum Tg and only performing it when there is a rise in serum Tg levels., (© 2025 John Wiley & Sons Ltd.)

Porcine reproductive and respiratory syndrome (PRRS) causes significant economic losses in the swine industry. However, the molecular mechanisms behind the common and cell type-specific systemic responses during PRRS virus (PRRSV) infection are not well understood. In this study, we collected viremia data, antibody levels, and whole-blood RNA-seq data obtained from eight PRRSV-infected piglets. We utilised a cell deconvolution approach to calculate cell type enrichment, constructed a time-serial gene co-expression network with differentially expressed genes, and conducted functional annotations. Three significant modules were identified within the network. The changes associated with viremia revealed an upregulated expression of genes related to antiviral activity. In the T-cell- and NK-cell-specific modules, infection led to an increased T-cell population and upregulation of genes related to T-cell defence responses. Conversely, in the monocyte- and neutrophil-specific module, genes involved in inflammatory responses were downregulated due to a decrease in monocyte proportion. This study highlights the time-series antiviral activities associated with viremia and the transcriptomic changes associated with immune responses in specific cell types. The findings provide comprehensive insights into host responses to PRRSV infection, including diagnostic biomarkers., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Objectives: This study evaluated the cost-effectiveness of using hearing aids among individuals aged 50 and older with varying levels of hearing loss in South Korea., Methods: A state-transition Markov model was employed to assess the cost-effectiveness of hearing aid utilization from a societal perspective. We simulated a cohort of patients aged 50, tracking their progression through normal, mild, moderate, and severe stages of hearing loss until death or age 80. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year gained was determined using both published and calculated data on the costs and effectiveness of hearing aids., Results: The respective ICERs were $8,571 for men and $10,635 for women. These figures are significantly below the willingness-to-pay (WTP) threshold of $31,721, which corresponds to the per capita gross domestic product in 2020. The probabilities of cost-effectiveness were 83.6% for men and 73.4% for women at this WTP threshold. The lower ICERs observed in men can likely be attributed to the earlier onset of hearing loss and the rapid progression from normal, mild, moderate, and severe stages of hearing loss to death., Conclusion: Hearing aids represent a highly cost-effective intervention for adults aged 50 and older in Korea, regardless of the degree of hearing loss, even in mild cases. In light of the rapidly aging population, it would be prudent for government policymakers to consider the costeffectiveness of hearing aids in their decision-making processes.

Electronic skins endow robots with sensory functions but often lack the multifunctionality of natural skin, such as switchable adhesion. Current smart adhesives based on elastomers have limited adhesion tunability, which hinders their effective use for both carrying heavy loads and performing dexterous manipulations. Here, we report a versatile, one-size-fits-all robotic adhesive skin using shape memory polymers with tunable rubber-to-glass phase transitions. The adhesion strength of our adhesive skin can be changed from minimal (~1 kilopascal) for sensing and handling ultralightweight objects to ultrastrong (>1 megapascal) for picking up and lifting heavy objects. Our versatile adhesive skin is expected to greatly enhance the ability of intelligent robots to interact with their environment.

Background: The present study aimed to compare outcomes between cholecystectomy on index versus delayed admission for acute cholangitis., Methods: The 2011-2020 Nationwide Readmissions Database was used to identify adult patients admitted for acute cholangitis who underwent cholecystectomy. Study cohorts were defined based on timing of surgery. Multivariable regressions and Royston-Parmar time-adjusted analysis were used to evaluate the association of cholecystectomy timing and outcomes., Results: Of 65,753 patients, 82.0 ​% received surgery on Index and 18.0 ​% on Delayed admissions. Following adjustment, Delayed operation was associated with significantly increased odds of mortality (AOR 1.67 [95 ​% CI 1.10-2.54]), complications (1.25 [1.13-1.40]), repair of bile duct injury (1.66 [1.15-2.41]), conversion to open (1.69 [1.48-1.93]), and 30-day readmission (3.52 [3.21-3.86]). The Delayed cohort experienced a +$14,200 increment in hospitalization costs relative to Index., Conclusions: Delayed cholecystectomy for acute cholangitis is significantly associated with adverse postoperative outcomes, suggesting that index cholecystectomy may be safe to perform., 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. Published by Elsevier Inc.)

Background: Mycophenolate mofetil (MMF) is usually prescribed with a reduced fixed dose in Asian kidney transplant recipients (KTRs). However, the clinical efficacy and safety of the fixed dose have not yet been investigated via therapeutic drug monitoring. We evaluated whether reduced fixed-dose MMF is an optimal dosing strategy to achieve the therapeutic target of mycophenolic acid (MPA) exposure in Korean KTRs., Methods: This open-label, prospective study enrolled 50 de novo KTRs prescribed with tacrolimus, corticosteroid, and fixed-dose MMF (1.0-1.5 g/day). The trough level (C0) and area under the curve (AUC0-12 hr) of MPA were measured at 1 and 24 weeks after kidney transplantation (KT). The relationship of body weight (BW)-adjusted MMF dose with MPA C0 and MPA AUC0-12 hr was assessed using linear regression analysis., Results: The initial fixed dose of MMF of 1.44 ± 0.16 g/day was adjusted in 24 patients (48.0%) and then reduced to a mean dose of 1.19 ± 0.31 g/day at 24 weeks after KT. Most patients (≥84.0%) attained the minimum required MPA C0 of 1.0 μg/mL and MPA AUC0-12 hr of 30 μg × hr/mL at 1 and 24 weeks. The BW-adjusted MMF dose demonstrated significant positive correlations with MPA C0 and MPA AUC0- 12 hr at 1 and 24 weeks after KT. Moreover, 14 patients (28.0%) reported MPA-related adverse events that were predictable based on MPA AUC0-12 hr (cutoff level, 46.4 μg × hr/mL)., Conclusion: The current reduced fixed-dose MMF strategy can help achieve the therapeutic target of MPA exposure in tacrolimus- treated Korean KTRs during the early posttransplant period.

Cervical cancer, which is mainly caused by oncogenic human papillomavirus subtypes, remains a significant global health challenge. Recent studies have indicated a connection between cervical cancer and the uterine microbiome, underscoring its importance. This study explored the potential of liquid-based cytology (LBC) samples, which are typically used for cytological analysis, in investigating the cervical microbiome. Thirty women participated in the study and provided clinical information. Three samples were obtained from each participant: one for clinical purposes using LBC, another for microbiome sampling using LBC, and a third using the SWAB Microbiome kit. The LBC and traditional swab (SWAB) samples were subjected to high-throughput 16S rRNA gene sequencing for microbiome analysis. The results revealed a consistent dominance of key taxa, particularly Lactobacillus spp. The analysis of differential abundance highlighted variations in microbial abundance among individuals, which were more prominent than those resulting from the sampling methods. Functional analysis identified arachidonic acid and alpha-linolenic acid metabolism, along with a cautionary note regarding the low mean proportion values. The network analysis revealed positive correlations between indicators of structure among the networks, highlighting the robustness of microbiome similarities despite the diversity of sampling methods. Supervised machine learning has revealed challenges in distinguishing LBC and SWAB samples based on their microbiome features. Weighted co-expression network analysis revealed that the correlation between microbial clusters and the sampling method with clinical data was not significant. This study emphasizes the similarity in microbial communities observed using the LBC and SWAB methods, highlighting the potential of using dual diagnostic approaches. Additionally, the use of residual LBC samples in large-scale microbiological studies can provide comprehensive insights into cervical health and disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Although thyroid tumors possessing isolated RAS mutations are generally considered to be indolent, the oncologic outcomes of tumors evaluated with comprehensive molecular testing have not been well characterized., Methods: We performed a retrospective cohort study of 368 consecutive patients with Bethesda III-VI thyroid nodules at a single institution (2016-2021) who underwent molecular testing with ThyroSeq v3. Patients with isolated RAS mutations were identified, and those with isolated BRAF V600E-mutated cancers were used as comparators. Outcomes of interest included rate of malignancy, high-risk histopathologic features, and structural disease recurrence., Results: A total of 50 patients (14%) had an isolated RAS-mutated nodule, of whom 41 underwent surgery (median age, 43 years; female, 83%). The malignancy rate on final pathology was 46%, whereas 32% of patients had noninvasive follicular thyroid neoplasm with papillary-like nuclear features and 22% had benign histopathology. In comparison, the isolated BRAF-mutated cohort (86 [24%] patients; median age, 45 years; female, 68%) had a 100% rate of malignancy. Only 2 (11%) of the isolated RAS patients with malignant histopathology had lymph node metastasis, compared with 34 (39%) of the BRAF cohort (P = .016). Over a median follow-up of 5 years, no patients with isolated RAS mutations had a structural recurrence compared with 5 patients (6%) in the isolated BRAF cohort., Conclusion: Bethesda III-VI thyroid nodules with isolated RAS mutations have a low rate of aggressive histopathologic features and are unlikely to recur. Thyroid lobectomy may be sufficient treatment for these tumors., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Background: Alopecia areata (AA) is characterized by an autoimmune inflammatory response to hair follicles. Several studies have suggested that infection and vaccination can trigger an autoimmune process around hair follicles. Moreover, reports of AA and various other autoimmune diseases have increased since the coronavirus disease 2019 (COVID-19) pandemic became established., Objective: We assessed the clinical characteristics and treatment response in patients who developed AA following COVID-19 infection or vaccination., Methods: This retrospective study involved patients who had developed COVID-19 or received a COVID-19 vaccination within 3 months before the onset or aggravation of AA from January 2020 to December 2022., Results: Fifty patients met the inclusion criteria. Eighteen patients had a history of COVID-19 infection, and 32 had a history of COVID-19 vaccination. The mean onset of AA after COVID-19 infection and vaccination was 5.22±3.35 and 4.13±2.73 weeks, respectively. The most common COVID-19-associated symptoms before AA were fever (88.9%) in the infection group and myalgia (50.0%) in the vaccination group. In the vaccination group, AA most commonly occurred after receiving the Pfizer-BioNTech vaccine (BNT162b2, 46.9%) or Moderna vaccine (mRNA-1273, 34.4%). The vaccination group showed more rapid improvement than the infection group; however, both showed significant improvement after 6 months of treatment of AA., Conclusion: We examined the clinical characteristics and treatment responses of patients who developed AA after COVID-19 infection or vaccination. Further research is needed to evaluate the detailed pathogenesis and association between COVID-19 and AA., Competing Interests: The authors have nothing to disclose., (© 2024 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Gastritis and gastric ulcers are common gastric diseases that are caused by infection, drugs, alcohol consumption, or stress. These conditions lead to increased inflammatory cytokines and recruitment of leukocytes, which damage the stomach mucosa and exacerbate disease severity. Sicyos angulatus (SA), an annual vine in the Cucurbitaceae family, is known to have an anti-inflammatory effect, but its efficacy for preventing gastritis and gastric ulcers has not yet been evaluated. In the present study, we investigated the gastroprotective effect of SA using a hydrochloric acid/ethanol-induced gastric mucosal injury mouse model and lipopolysaccharide (LPS)-stimulated KATO III cells. Macroscopic analysis revealed a reduction in gastric ulcer area. Similarly, histopathological analysis showed a dose-dependent decrease in gastric mucosal injury, with significant improvement at 750 mg/kg of SA treatment. Gene expressions of inflammatory cytokines, chemokines, and adhesion molecule were reduced in the SA-administered group. Immunohistochemical staining indicated that SA significantly decreased neutrophil infiltration in the lamina propria and epithelium of the stomach. Kaempferol, a major bioactive flavonoid of SA, also improved gastric injury by reducing macroscopic and microscopic lesions, inflammatory mediator gene expression, and neutrophil infiltration. Furthermore, both SA and kaempferol downregulated LPS-mediated increases in inflammatory cytokines and chemokines following inhibition of p38 and c-Jun N-terminal kinase (JNK) phosphorylation in KATO III cells. These results suggest that SA can ameliorate gastric mucosal injury by inhibiting the recruitment of inflammatory cells, particularly neutrophils, and by suppressing p38 and JNK phosphorylation.

Background and Objectives: The immersive virtual reality (VR) simulator is advantageous because it is cost-effective, realistic, can be controlled directly by the user, and can be integrated into education and training in otorhinolaryngology. The present study explored the feasibility of incorporating VR pure-tone audiometry (PTA) into an audiologist training curriculum, and assessed audiology experts' willingness to use a VR PTA., Materials and Methods: A total of 31 audiologists (16 skilled audiologists and 15 undergraduate students) participated in the study, using a developed VR PTA application with a Meta Quest 2 device. A digital twin technique was applied for a realistic environment. The study measured key components of the VR system and behavioral intention to use VR PTA and traditional PTA using a modified version of the Technology Acceptance Model survey. The survey outcomes for VR PTA and the traditional PTA were compared, using a paired t -test and W test., Results: The general characteristics of the participants were homogeneous. In the homogeneity test, no statistically significant differences were found between the ratings of VR PTA and traditional PTA. The comparison between VR PTA and traditional PTA revealed no significant differences between skilled audiologists and undergraduate students for all variables., Conclusions: The VR PTA and traditional PTA had no differences in of VR system characteristics and behavioral intention to use. The efficacy of the VR PTA was validated, and previous experience with traditional PTA was not affected by adopting VR PTA. Further studies are needed to assess performance enhancements in audiological testing through VR simulation., Competing Interests: 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., (© 2024 Published by Elsevier Ltd.)

Due to the higher risk of medical complications posed by influenza infection, patients with type 1 diabetes (T1D) are strongly recommended to receive the influenza vaccine. However, it remains unclear if hyperglycemia in patients with T1D affects vaccine-induced immune responses. In this study, we investigated the humoral and cellular immune responses of prediabetic and diabetic, nonobese diabetic (NOD) mice following influenza vaccination to determine the effects of hyperglycemia on influenza vaccine-induced responses. In diabetic NOD mice, vaccine-specific IgG and IgM levels, as well as IgG-producing cells, were comparable to those in prediabetic NOD mice. However, the diabetic NOD mice exhibited reduced percentages of memory T cells and activated T cells in the spleen, along with reduced number of vaccine-specific interferon (IFN)-γ-secreting cells. Thus, these findings suggest that in patients with T1D, hyperglycemia could lead to impaired cell-mediated immune responses following influenza 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.)

Despite the significant threat of heat stress to livestock animals, only a few studies have considered the potential relationship between broiler chickens and their microbiota. Therefore, this study examined microbial modifications, transcriptional changes and host-microbiome interactions using a predicted metabolome data-based approach to understand the impact of heat stress on poultry. After the analysis, the host functional enrichment analysis revealed that pathways related to lipid and protein metabolism were elevated under heat stress conditions. In contrast, pathways related to the cell cycle were suppressed under normal environmental temperatures. In line with the transcriptome analysis, the microbial analysis results indicate that taxonomic changes affect lipid degradation. Heat stress engendered statistically significant difference in the abundance of 11 microorganisms, including Bacteroides and Peptostreptococcacea . Together, integrative approach analysis suggests that microbiota-induced metabolites affect host fatty acid peroxidation metabolism, which is correlated with the gene families of Acyl-CoA dehydrogenase long chain ( ACADL ), Acyl-CoA Oxidase ( ACOX ) and Acetyl-CoA Acyltransferase ( ACAA ). This integrated approach provides novel insights into heat stress problems and identifies potential biomarkers associated with heat stress.

Background: There are few studies that have examined clinical and radiological outcomes at 5 years after isolated medial patellofemoral ligament (MPFL) reconstruction. To date, midterm outcomes after isolated double-bundle (DB) MPFL reconstruction are not well known., Hypothesis: Isolated DB MPFL reconstruction using a patellar suture anchor technique would lead to improved functional scores and radiological findings, and these improvements would remain stable over the 5-year postoperative period., Study Design: Case series; Level of evidence, 4., Methods: Isolated MPFL reconstruction was performed in patients with recurrent patellar instability between March 2013 and February 2017. Clinical and functional evaluations were performed via an interview using the Kujala, Lysholm, and Tegner scores preoperatively and at 6, 12, 24, and 60 months postoperatively. Radiographs were taken preoperatively, immediately postoperatively, and at 24 and 60 months after surgery. Radiographic assessments included measuring the modified Insall-Salvati ratio, congruence angle, and lateral patellofemoral angle., Results: A total of 31 patients (31 knees) underwent isolated MPFL reconstruction; 4 patients did not complete 5-year follow-up, and thus, 27 patients (27 knees) were enrolled in the study. The mean age at the time of surgery was 22.0 ± 6.4 years (range, 14-32 years). All clinical and functional scores significantly improved in the first 2 years ( P < .001), with the mean Kujala, Lysholm, and Tegner scores improving from 52.7 to 90.7, 49.6 to 92.7, and 2.9 to 5.1, respectively. There was no significant difference in scores between 2- and 5-year follow-up. All radiographic parameters significantly improved between preoperatively and immediately postoperatively ( P < .001), with mean values for the modified Insall-Salvati ratio, congruence angle, and lateral patellofemoral angle improving from 1.7° to 1.6°, 5.7° to -6.6°, and 3.0° to 5.9°, respectively. No significant differences were observed in radiographic measurements between the postoperative time points. No patients experienced a patellar redislocation or fracture., Conclusion: The prospective analysis of isolated DB MPFL reconstruction at 5-year follow-up showed that clinical and radiological outcomes significantly improved postoperatively and were maintained to 5 years. These midterm results suggest that isolated DB MPFL reconstruction is an effective treatment option for patients with patellar instability., Competing Interests: The authors have declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Osteoporosis is a common skeletal disease, primarily associated with aging, that results from decreased bone density and bone volume. This reduction significantly increases the risk of fractures in osteoporosis patients compared to individuals with normal bone density. Additionally, the bone regeneration process in these patients is slow, making complete healing difficult. Along with the decline in bone volume and density, osteoporosis is characterized by an increase in marrow adipose tissue (MAT), which is fat within the bone. In this altered bone microenvironment, osteoblasts are influenced by various factors secreted by adipocytes. Notably, saturated fatty acids promote osteoclast activity, inhibit osteoblast differentiation, and induce apoptosis, further reducing osteoblast formation. In contrast, monounsaturated fatty acids inhibit osteoclast formation and mitigate the apoptosis caused by saturated fatty acids. Leveraging these properties, we aimed to investigate the effects of overexpressing stearoyl-CoA desaturase 1 (SCD1), an enzyme that converts saturated fatty acids into monounsaturated fatty acids, on osteogenic differentiation and bone regeneration in both in vivo and in vitro models. Through this novel approach, we seek to develop a stem cell-based therapeutic strategy that harnesses SCD1 to improve bone regeneration in the adipocyte-rich osteoporotic environment.

Background/Objectives: The optimal graft, particularly in combined anterior cruciate ligament (ACL) and medial collateral ligament (MCL) injuries, remains controversial. We evaluated the influence of graft choice between bone-patellar tendon-bone (BPTB) and hamstring autografts on clinical outcomes in combined ACL and MCL injuries. Methods: This retrospective analysis included patients with concurrent ACL and MCL injuries who underwent single-bundle ACL reconstruction with BPTB (group B) or hamstring (group H) grafts, between 2010 and 2019, with a ≥2-year follow-up. Patients were classified based on the MCL injury grade (I, II, or III). Clinical outcomes were assessed through knee stability evaluations using valgus stress radiographs and the KT-2000 arthrometer, patient-reported outcomes using the International Knee Documentation Committee (IKDC) subjective score and Lysholm score, and radiologic outcomes using the IKDC radiographic grade. Results: The study included 169 patients (group B, 92; group H, 77). No significant between-group differences in knee stability or functional outcomes were found after follow-up. Within the same MCL injury grade, particularly in high-grade MCL injuries, BPTB grafts resulted in significantly better medial stability (side-to-side difference in medial joint opening on valgus stress radiographs: grade II, p = 0.006; grade III, p = 0.039) and functional outcomes (IKDC subjective score: grade II, p = 0.045; grade III, p = 0.038) than hamstring grafts. In the hamstring group, higher-grade MCL injuries were associated with worse outcomes (Lysholm knee score, p = 0.009; IKDC subjective score, p = 0.015). Conclusions: Graft choice in ACL reconstruction with concomitant MCL injuries may affect clinical outcomes, particularly in high-grade MCL injuries. Although both graft types performed similarly overall, BPTB grafts provided superior medial stability and functional results in higher-grade MCL injuries. However, caution is needed when interpreting these results due to limitations such as the small sample size and the lack of randomization in graft selection.

Viruses have long been recognized as significant pathogens, contributing to multiple global pandemics throughout human history. Recent examples include the 2009 influenza pandemic and the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. Despite ongoing experimental and clinical efforts, the development of effective antiviral treatments and vaccines remains challenging due to the high mutation rates of many human pathogenic viruses including influenza virus and SARS-CoV-2. As an alternative approach, antiviral strategies targeting host factors shared by multiple viruses could provide a more universally applicable solution. Emerging evidence suggests that viruses exploit the host cytoskeletal network to facilitate efficient viral replication and propagation. Therefore, a comprehensive understanding of the interactions between viral components and the cytoskeletal machinery may offer valuable insights for the development of broad-spectrum antiviral therapeutics. This review compiles and discusses current knowledge on the interactions between viruses and cytoskeletal elements, including kinesin, dynein, myosin, and vimentin, and explores their potential as therapeutic targets. The potential for these cytoskeletal components to serve as targets for new antiviral interventions is discussed in the context of diverse human viruses, including influenza virus, SARS-CoV-2, herpes simplex virus, human papillomavirus, and human immunodeficiency virus., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

This study focused on the efficient post-transcriptional incorporation of a modified nucleoside at the end of the poly-A tail of mRNA. The modified mRNA was obtained in high yield and served to enhance protein expression. Utilizing poly-U polymerase, our method successfully enabled a single 2'OMeU residue to be incorporated into mRNA, which unexpectedly provided significant stabilization, even with only a single incorporation, to enhance the resistance of mRNA to degradation by cellular exonuclease. This stabilization effect allowed the mRNA to remain viable within the cell for an extended period to ultimately increase the translation efficiency at least 3-fold. This approach to mRNA modification at the 3' end with a single 2'OMeU residue, by utilizing a straightforward tailing method, surpasses other ligation methods in terms of mRNA modification efficiency. Collectively, our results highlight the potential of this method to significantly advance the development of highly effective mRNA-based therapies in the future.

The White Blood Cell (WBC) differential test ranks as the second most frequently performed diagnostic assay. It requires manual confirmation of the peripheral blood smear by experts to identify signs of abnormalities. Automated digital microscopy has emerged as a solution to reduce this labor-intensive process and improve efficiency. Several publicly available datasets provide various WBC subtypes of differing quality and resolution. These datasets have contributed to advancing WBC classification using machine learning techniques. However, digital microscopy of blood cells with high magnification often requires a wider depth of field, posing challenges for automatic digital microscopy that necessitates capturing multiple stacks of focal planes to obtain complete images of specific blood cells. Our dataset provides 25,773 image stacks from 72 patients. The image labels consist of 18 classes encompassing normal and abnormal cells, with two experts reviewing each label. Each image includes 10 z-stacks of cropped 200 by 200 pixel images, captured using a 50X microscope with 400 nm intervals. This study presents a comprehensive multi-focus dataset for WBC classification., (© 2024. The Author(s).)

Early peritoneal dialysis (PD)-related infection is a severe complication. This study investigated the relationship between patient-doctor contact (PDC) duration and early PD-related infection. In the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) Korea, incident dialysis patients receiving PD were divided into two groups based on PDC duration (< 15 min versus ≥ 15 min), which was defined as the duration a nephrologist typically spends with a patient receiving PD during each visit according to the facility practice pattern. Early risks of PD-related infections, such as peritonitis and catheter-related infection (onset within 3 and 12 months of PD), were compared to the PDC duration using Cox regression. The study included 276 patients (184 [66.7%] in the shorter PDC group [< 15 min] and 92 [33.3%] in the longer PDC group [≥ 15 min]). The average age did not differ between the groups. The incidences of 3- and 12-month PD-related infections were significantly lower in the longer PDC group than in the shorter PDC group (3 months: 1.1% versus 9.8%, P = 0.007; 12 months: 9.8% versus 23.4%, P = 0.007). Longer PDC was independently associated with a lower risk of PD-related infections at 3 and 12 months (3 months: adjusted hazard ratio [aHR], 0.11; 95% confidence interval [CI], 0.02-0.85, P = 0.034; 12 months: aHR, 0.43; 95% CI 0.19-0.99, P = 0.048). Overall, a longer PDC duration was associated with a significantly lower risk of early PD-related infection., (© 2024. The Author(s).)

The auditory brainstem response (ABR) is a noninvasive test that measures neural activity in response to auditory stimuli. Racial differences in head shape have provided strong evidence for specific normative data and accurate device calibration. International standards emphasize the need for standardized procedures and references. This study aimed to outline the standard procedure and related normative ABR values. Standard procedures were performed according to International Electrotechnical Commission (IEC) standards. Five studies from two countries were included to compare the normative values of the ABR. The dataset from the National Standard Reference Data Center (NSRDC) was used as reference. Normative values were described in terms of stimuli, latency, and amplitude. For click stimuli, the latency of the ABR showed different patterns across populations, such as those from Korea and the USA. Although the latencies reported by the NSRDC and for Koreans were relatively short, those reported for USA populations were longer. Using clicks, it was shown that the USA population had the largest ABR amplitude compared to those reported for the other two datasets. For Wave V latency using tone bursts, a similar pattern was identified with click stimuli. Frequency-specific trends were also observed. Although there is a lack of ABR datasets, the information and insights of the present study could be utilized as standard guidelines in research on ABR.

Background: Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses., Objective: We investigated the safety and efficacy of allogenic human bone marrow-derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD)., Methods: The study included a phase 1 open-label trial followed by a phase 2 randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD., Results: In phase 1, intravenous administration of hcMSCs at 2 doses (1 × 10 6 and 5 × 10 5 cells/kg) was safe and well tolerated in 20 subjects. Because there was no difference between the 2 dosage groups (P = .9), it was decided to administer low-dose hcMSCs only for phase 2. In phase 2, subjects receiving 3 weekly intravenous infusions of hcMSCs at 5 × 10 5 cells/kg showed a higher proportion of an Eczema Area and Severity Index (EASI)-50 response at week 12 compared to the placebo group (P = .038). The differences between groups in the Dermatology Life Quality Index and pruritus numeric rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period., Conclusions: The hcMSC treatment resulted in a significantly higher rate of EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSC treatment was acceptable. Further larger-scale studies are necessary to confirm these preliminary findings., Competing Interests: Disclosure statement Supported in part by SCM Lifescience Inc. Disclosure of potential conflict of interest: H.-M. Seo, B.-L. Lew, Y. W. Lee, S. W. Son, C. O. Park, Y. L. Park, J.-O. Baek, M. K. Shin, D. H. Kim, D. H. Lee, Y. H. Jang, H.-C. Ko, C.-H. Na, Y.-J. Seo, and G. S. Choi are investigators in clinical trials for SCM Lifescience Inc. D.-S. Ham and D. H. Kim are employees of SCM Lifescience Inc., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Thyroid storm is a rare but potentially lethal manifestation of thyrotoxicosis. Guidelines recommend nonoperative management of thyroid storm, but thyroidectomy can be performed if patients fail medical therapy or need immediate resolution of the storm. Outcomes of thyroidectomy for management of thyroid storm remain ill-defined., Methods: Using the National Inpatient Sample from 2016 to 2020, a retrospective analysis was conducted of patients admitted with thyroid storm. Outcomes of interest included operative complications and mortality. Multivariable logistic regression was performed to assess factors associated with receiving thyroidectomy and mortality., Results: An estimated 16,175 admissions had a diagnosis of thyroid storm. The incidence of thyroid storm increased from .91 per 100,000 people in 2016 to 1.03 per 100,000 people in 2020, with a concomitant increase in mortality from 2.9% to 5.3% ( P < .001). Operative intervention was pursued in 635 (3.9%) cases with a perioperative complication rate of 30%. On multivariable regression, development of acute decompensated heart failure (adjusted odds ratio [AOR] 1.66, 95% Confidence Interval [CI] 1.03-2.68, P = .037) and acute renal failure (AOR 2.10, 95% CI 1.17-3.75, P = .013) increased odds of receiving surgery. The same multivariable model did not show a significant association between thyroidectomy and mortality., Discussion: The incidence of thyroid storm and associated mortality increased during the study period. Thyroidectomy is rarely performed during the same admission, with an overall perioperative complication rate of 30% and no effect on mortality. Patients with acute decompensated heart failure and renal failure were more likely to receive an operative intervention., 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.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that requires a complex management strategy, which often involves multiple and diverse topicals and systemic treatment regimens. While topical steroids and more recently calcineurin inhibitors have been the mainstay therapy for mild-to-moderate disease, recent advances in the understanding of AD pathogenesis have led to the development of different new targets, rapidly widening our therapeutic armamentarium. This review summarizes their efficacy and safety data. We also review topical optimization strategies, including the recently published topical volume calculator, to maximize long-term disease control, especially when using multiple agents at the same time., Competing Interests: Disclosure L.F. Eichenfield has served as a consultant, speaker, advisory board member, or investigator for AbbVie, Amgen, Apogee, Arcutis, Aslan, Attovia, Bristol-Myers Squibb, Castle Biosciences, Dermavant, Eli Lilly, Forte, Galderma, Incyte, Janssen, Johnson & Johnson, LEO Pharma, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi-Genzyme, Target RWE and UCB. M.G. Buethe, C. Kellogg, Y.J. Seo, and C. Vuong have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Alopecia areata (AA) has a poor clinical course in children. There are no reliable therapeutic options for children with severe AA, including alopecia totalis (AT) and alopecia universalis (AU)., Objectives: We evaluated the efficacy and adverse effects of a potent topical corticosteroid (TCS) under occlusion in paediatric patients with severe AA., Methods: We reviewed records of 23 patients under the age of 10 years with AT or AU treated with a potent TCS (0.05% clobetasol propionate or 0.3% diflucortolone valerate) for 8 h under occlusion with a plastic film. We used the Severity of Alopecia Tool (SALT) to measure clinical improvement. The primary endpoint was a SALT score of ≤ 20 at 6 months. We analysed the change in cortisol levels to identify the long-term safety of TCS therapy on the hypothalamus-pituitary-adrenal axis., Results: Nineteen of the 23 patients (83%) reached SALT ≤ 20 at 6 months. Six patients relapsed over the 6-month follow-up period. Four patients were suspected of having adrenal insufficiency. However, the cortisol levels of the patients recovered to normal within 1 month of lowering the TCS potency or changing to nonsteroidal treatments. Limitations include the retrospective design and small sample size., Conclusions: This study shows that a potent TCS occlusion may be a safe treatment option in paediatric patients with severe AA. Further long-term studies are required to evaluate the safety and recurrence of TCS occlusion therapy for paediatric AA., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Published by Oxford University Press on behalf of British Association of Dermatologists 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: The geriatric nutritional risk index (GNRI) can easily identify malnutrition-associated morbidity and mortality. We investigated the association between preoperative GNRI and 30-d mortality in geriatric burn patients who underwent surgery., Methods: The study involved geriatric burn patients (aged ≥ 65 y) who underwent burn surgery between 2012 and 2022. The GNRI was computed using the following formula: 1.489 × serum albumin concentration (mg/L) + 41.7 × patient body weight/ideal body weight. Patients were dichotomized into the high GNRI (≥ 82) and low GNRI (< 82) groups. GNRI was evaluated as an independent predictor of 30-d postoperative mortality. The study also evaluated the association between GNRI and sepsis, the need for continuous renal replacement therapy (CRRT), major adverse cardiac events (MACE), and pneumonia., Results: Out of 270 patients, 128 (47.4%) had low GNRI (< 82). Multivariate Cox regression analysis revealed that low GNRI was significantly associated with 30-d postoperative mortality (hazard ratio: 1.874, 95% confidence interval [CI]: 1.146-3.066, P = 0.001). Kaplan-Meier analysis revealed that the 30-day mortality rate differed significantly between the low and high GNRI groups (log-rank test, P < 0.001). The 30-d postoperative mortality (hazard ratio: 2.677, 95% CI: 1.536-4.667, P < 0.001) and the incidence of sepsis (odds ratio [OR]: 2.137, 95% CI: 1.307-3.494, P = 0.004), need for CRRT (OR: 1.919, 95% CI: 1.101-3.344, P = 0.025), MACE (OR: 1.680, 95% CI: 1.018-2.773, P = 0.043), and pneumonia (OR: 1.678, 95% CI: 1.019-2.764, P = 0.044), were significantly higher in the low GNRI group than in the high GNRI group., Conclusions: Preoperative low GNRI was associated with increased 30-d postoperative mortality, sepsis, need for CRRT, MACE, and pneumonia in geriatric burn patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Solid-organ transplant recipients (SOTRs) receiving immunosuppressive therapy are expected to have worse clinical outcomes from coronavirus disease 2019 (COVID-19). However, published studies have shown mixed results, depending on adjustment for important confounders such as age, variants, and vaccination status., Materials and Methods: We retrospectively collected the data on 7,327 patients hospitalized with COVID-19 from two tertiary hospitals with government-designated COVID-19 regional centers. We compared clinical outcomes between SOTRs and non-SOTRs by a propensity score-matched analysis (1:2) based on age, gender, and the date of COVID-19 diagnosis. We also performed a multivariate logistic regression analysis to adjust other important confounders such as vaccination status and the Charlson comorbidity index., Results: After matching, SOTRs (n=83) had a significantly higher risk of high-flow nasal cannula use, mechanical ventilation, acute kidney injury, and a composite of COVID-19 severity outcomes than non-SOTRs (n=160) (all P <0.05). The National Early Warning Score was significantly higher in SOTRs than in non-SOTRs from day 1 to 7 of hospitalization ( P for interaction=0.008 by generalized estimating equation). In multivariate logistic regression analysis, SOTRs (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.12-4.11) and male gender (OR, 2.62; 95% CI, 1.26-5.45) were associated with worse outcomes, and receiving two to three doses of COVID-19 vaccine (OR, 0.43; 95% CI, 0.24-0.79) was associated with better outcomes., Conclusion: Hospitalized SOTRs with COVID-19 had a worse prognosis than non-SOTRs. COVID-19 vaccination should be implemented appropriately to prevent severe COVID-19 progression in this population., Competing Interests: No conflict of interest., (© 2024 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, The Korean Society for AIDS, and Korean Society of Pediatric Infectious Diseases.)

In this study, we developed an isothermal fluorometric diagnostic method for DNA virus-generating disorders such as Mpox. Our results showed that the release of a large number of protons during multiplex-LAMP markedly lowered the pH level, which transformed the retinoblastoma (Rb) linear ssDNA into i-motifs. Consequently, thiazole orange (TO; a fluorometric probe sensitive to the i-motif) boosted the signal-on fluorescence because of its ability to bind selectively to i-motifs. This multiplex-LAMP/i-motif-TO system enabled simultaneous detection aimed at numerous potential targets with remarkable sensitivity (1.47 pg per mL) and efficiency (30 minutes). Our method is expected to enable DNA-virus-related diseases to be efficiently and accurately assessed.

Transcription factors specifically bind to their consensus sequence motifs and regulate transcription efficiency. Transcription factors are also able to non-specifically contact the phosphate backbone of DNA through electrostatic interaction. The homeodomain of Meis1 TALE human transcription factor (Meis1-HD) recognizes its target DNA sequences via two DNA contact regions, the L1-α1 region and the α3 helix (specific binding mode). This study demonstrates that the non-specific binding mode of Meis1-HD is the energetically favored process during DNA binding, achieved by the interaction of the L1-α1 region with the phosphate backbone. An NMR dynamics study suggests that non-specific binding might set up an intermediate structure which can then rapidly and easily find the consensus region on a long section of genomic DNA in a facilitated binding process. Structural analysis using NMR and molecular dynamics shows that key structural distortions in the Meis1-HD-DNA complex are induced by various single nucleotide mutations in the consensus sequence, resulting in decreased DNA binding affinity. Collectively, our results elucidate the detailed molecular mechanism of how Meis1-HD recognizes single nucleotide mutations within its consensus sequence: (i) through the conformational features of the α3 helix; and (ii) by the dynamic features (rigid or flexible) of the L1 loop and the α3 helix. These findings enhance our understanding of how single nucleotide mutations in transcription factor consensus sequences lead to dysfunctional transcription and, ultimately, human disease., (© 2024. The Author(s).)

The demand-resources model of stress posits that parenting tasks and expectations of mothers that exceed their resources are likely to tax their psychological well-being. Social and instrumental support from spouse or family may help alleviate the negative effects of parenting stress on mothers' psychological well-being. However, parenting stress and its impact have been less studied among immigrant mothers. Moreover, the sources of family support (i.e., spousal and other family members) might interactively affect mothers' well-being in the face of parenting stress. Therefore, the present study aimed to examine whether support from the spouse and other family members jointly buffers against the long-term psychological effects of parenting stress on Chinese immigrant mothers' life satisfaction. Data were collected from 273 Chinese American mothers at two time points separated by 6 months. A three-way interaction was conducted to examine the complementary protective effect of perceived support mothers received from their spouses and their other family members combined. Results showed that after controlling for the covariates, parenting stress was only longitudinally associated with changes in maternal life satisfaction when support from both spouse and other family members was low. Our findings highlight the complementary protective effects of spousal support and nonspouse family members' support in alleviating parenting stress of mothers and its adverse impact on lowering mothers' life satisfaction 6 months later. Theoretical and applied implications of these findings are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background and Objectives: Neoadjuvant chemotherapy (NAC) is becoming favored for all pancreatic adenocarcinoma (PDAC). Patients with seemingly resectable disease infrequently still display vascular involvement intraoperatively. Outcomes following NAC versus upfront surgery in patients undergoing pancreaticoduodenectomy (PD) with vascular resection are unknown., Methods: We performed a retrospective cohort study of PDAC patients who underwent PD with vascular resection between January 1, 2013, to December 31, 2020, within a single academic center. Clinicopathologic characteristics and disease-free survival (DFS) were compared between NAC versus upfront surgery cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model., Results: Eighty-one patients who underwent PD with vascular resection for PDAC were included. Forty-six patients (56%) received NAC. The NAC cohort more often had pathologic N0 status (47.8% vs. 8.6%, p < 0.001), had decreased vascular invasion (11% vs. 40%, p = 0.002), and completed chemotherapy (80% vs. 40%, p < 0.01). The NAC cohort demonstrated improved DFS (40.5 vs. 14.3 months, p = 0.007). In multivariable analysis, NAC remained independently associated with increased DFS (HR = 0.48, p = 0.02)., Conclusions: NAC was associated with improved clinicopathologic outcomes and DFS in PD with vascular resection. These findings demonstrate the advantage of NAC in PDAC patients undergoing PD with vascular resection., (© 2024 Wiley Periodicals LLC.)