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With advances in materials science and medical technology, wearable sensors have become crucial tools for the early diagnosis and continuous monitoring of numerous cardiovascular diseases, including arrhythmias, hypertension and coronary artery disease. These devices employ various sensing mechanisms, such as mechanoelectric, optoelectronic, ultrasonic and electrophysiological methods, to measure vital biosignals, including pulse rate, blood pressure and changes in heart rhythm. In this Review, we provide a comprehensive overview of the current state of wearable cardiovascular sensors, focusing particularly on those that measure blood pressure. We explore biosignal sensing principles, discuss blood pressure estimation methods (including machine learning algorithms) and summarize the latest advances in cuffless wearable blood pressure sensors. Finally, we highlight the challenges of and offer insights into potential pathways for the practical application of cuffless wearable blood pressure sensors in the medical field from both technical and clinical perspectives., Competing Interests: Competing interests: The authors declare no competing interest., (© 2025. Springer Nature Limited.)

Phototherapy based on micro light-emitting diodes (µLEDs) has gained enormous attention in the medical field as a patient-friendly therapeutic method due to its advantages of minimal invasiveness, fewer side effects, and versatile device form factors with high stability in biological environment. Effective cosmetic and medical phototherapy depends on deep light penetration, precise irradiation, and simultaneous multi-site stimulation, facilitated by three-dimensional (3D) optoelectronics specifically designed for complex human matters, defined here as 3D µLEDs. This perspective article aims to present the functionalities and strategies of 3D µLEDs for human-centric phototherapy. This study investigates the effectiveness of phototherapy enabled by three key functionalities such as shape morphing, self-adaptation, and multilayered spatiotemporal mapping of 3D µLEDs. Finally, this article provides future insights of 3D µLEDs for human-centric phototherapy applications., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Proline is a major substrate in collagen biosynthesis and is required for collagen molecule formations. However, detailed explanations of the molecular basis through which proline functions in collagen biosynthesis have yet to be provided. Thus, genome-wide screening was employed to elucidate these in the pre-osteoblastic MC3T3-E1 and human periodontal ligament fibroblast (hPDLF) cell lines. Indeed, both cell lines represent important sources for collagen biosynthesis and tissue regeneration in the dental region, specifically treating extracellular proline during cultivations. The altered gene expression patterns were identified, and the precise expression patterns were confirmed by microarray. Cell viability and osteogenic differentiation patterns were examined using a range of experimental methods, such as the MTS assay, ALP staining, ARS staining, and collagen (COL)-type1A ELISA. Overall, we revealed a cell line-specific function of exogenous proline in collagen biosynthesis during osteogenic differentiation conditions with the candidate signaling pathways. These putative signaling networks could represent plausible answers to understanding collagen biosynthesis for regenerating connective tissues such as skin, muscle, and bone., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: Not applicable. Informed consent: Not applicable., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Controlled photooxidation-mediated disruption of collagens in the tumor microenvironment can reduce desmoplasia and enhance immune responsiveness. However, achieving effective light delivery to solid tumors, particularly those with dynamic volumetric changes like pancreatic ductal adenocarcinoma (PDAC), remains challenging and limits the repeated and sustained photoactivation of drugs. Here, 3D, shape-morphing, implantable photonic devices (IPDs) are introduced that enable tumor-specific and continuous light irradiation for effective metronomic photodynamic therapy (mPDT). This IPD adheres seamlessly to the surface of orthotopic PDAC tumors, mitigating issues related to mechanical mismatch, delamination, and internal lesions. In freely moving mouse models, mPDT using the IPD with close adhesion significantly reduces desmoplastic tumor volume without causing cytotoxic effects in healthy tissues. These promising in vivo results underscore the potential of an adaptable and unidirectional IPD design in precisely targeting cancerous organs, suggesting a meaningful advance in light-based therapeutic technologies., (© 2024 Wiley‐VCH GmbH.)

A novel water-soluble root canal filling material based on sodium iodide (NaI) has been developed to overcome the limitations of existing iodine-based formulations. However, the biological stability of this approach in animal studies remains unverified. This study evaluated the biocompatibility of NaI compared to commercial root canal filling materials (Calcipex II and Vitapex ® ) in pulpectomized canine teeth to assess its clinical applicability. Following a four-week observation period, none of the experimental groups exhibited tooth mobility or fistula formation. Radiographic and micro-CT analyses revealed no radiolucency in periapical lesions. Histopathologic evaluation demonstrated the absence of inflammatory responses in periapical regions across all material groups, with histological inflammation scoring 0. High-magnification histological examination of periapical areas showed well-preserved periodontal ligament tissue in all groups. Despite certain limitations of NaI-based fillings in the pulp cavity, including loss of radiopacity and tooth discoloration, NaI demonstrates potential as a safe and effective alternative for pulp filling material, particularly due to its minimal risk of root resorption and inflammatory response.

Photobiomodulation therapy based on micro light-emitting diodes (µLEDs) holds remarkable potential for the beauty industry. Here, a cosmetically effective face-fit surface-lighting µLED mask for skin anti-aging is introduced. The face-conformable mask enables deep tissue treatment through proximal light irradiation, with a 3D origami structure capable of adapting to complex facial contours with closed adherence. A blister-assisted laser transfer achieves rapid and accurate µLEDs transfer at a high throughput of 50 chips per second, facilitating a mass-producible and large-area process. Finally, clinical trials demonstrate significant improvements in elasticity, sagging, and wrinkles across six facial areas, with a maximum enhancement of 340% in deep skin elasticity of the perioral area compared to the conventional LED mask group., (© 2024 Wiley‐VCH GmbH.)

Background: The incidence of monoclonal gammopathy of undetermined significance (MGUS) in the population of over 50-year-olds is approximately 3% and increases with age. The association between MG and neuropathy has been of interest for several years, but the causal relationship has not yet been clarified., Methods: For 682 patients who visited the Department of Neurology and requested tests for MG work-up, we retrospectively collected demographic and clinical information, such as age, gender, diagnosis, and neurologic and laboratory test results, from their medical records., Results: Out of a total of 682 patients who were suspected of neuropathy and tested for monoclonal gammopathy (MG), twelve (1.76%) showed MG on their serum protein electrophoresis. The most common form was IgM-κ with five patients, followed by IgG-κ, IgG-λ, and biclonal IgG-λ and IgA-κ. The results of the immunoglobulin quantitation test and free light chain assay showed that involved M-protein values in these patients were increased. Some patients were positive for anti-myelin-associated glycoprotein (MAG) antibody, anti-GD1b IgM antibody, anti-GM1 IgG & IgM antibody, and anti-cardiolipin IgM antibody. Also, some had antinuclear antibody (ANA) or antineutrophil cytoplasmic antibody (ANCA)., Conclusions: In the future, it is necessary to investigate the pathogenic relationship between M-protein and autoantibodies in patients with neuropathies.

Background and Objectives: Frequency-lowering (FL) algorithms improve the audibility of high-frequency sounds by shifting inaudible high-frequency components to audible low-frequency regions. However, the FL algorithm has yielded mixed findings. This study involved two experiments. The first experiment investigated whether objective and subjective auditory outcomes would be enhanced by activating frequency composition (Fcomp), which is a type of FL technique. The second experiment determined whether auditory training with Fcomp activation would provide perceptual benefits to older hearing aid users., Subjects and Methods: Twelve older hearing aid users with moderate to profound high-frequency sensorineural hearing loss participated in this study. In Experiment I, all participants received a 4-week adaptation period to Fcomp before the measurement, and then the influence of Fcomp was evaluated. In Experiment II, among the 12 participants in Experiment I, five received 8-week phoneme-based auditory training while activating Fcomp, whereas the remaining seven did not receive training but continued to use Fcomp as non-trained controls., Results: In Experiment I, 4-week passive accli-matization period to Fcomp did not improve speech-in-quiet recognition or self-perceived sound quality. In Experiment II, active pho-neme-based training enhanced recognition of consonants and words as well as better speech-quality ratings for trained participants. The consecutive use of Fcomp did not lead to any differences for non-trained participants., Conclusions: Overall, phoneme-based auditory training would allow older hearing aid users to relearn frequency-lowered speech sounds and reduce phonetic confusion. However, the analytical training approach did not lead to transfer to sentence recognition or overall satisfaction with the hearing aids.

Background/Objectives : We aimed to investigate the relationship between deformational plagiocephaly (DP) severity and anterior fontanelle size and to explore the connection between fontanelle size and developmental delay. Methods : We enrolled 189 (122 boys and 67 girls; mean corrected age, 119.79 days) of the 256 infants who visited our clinic for plagiocephaly between March 2022 and June 2023. This study analyzed the correlation between cranial vault asymmetry (CVA) and anterior fontanelle size as measured using skull anteroposterior (AP) radiography and ultrasonography. The severity of DP was graded from minimal to severe based on the Argenta classification. Infants were grouped according to CVA severity as follows: Group 1 (CVA ≤ 5 mm), Group 2 (5 mm < CVA < 10 mm), and Group 3 (CVA ≥ 10 mm). Additionally, 40 infants underwent the Denver Developmental Screening Test II (DDST-II) for neurodevelopmental delays and were divided into groups based on the presence or absence of developmental delays for fontanelle size comparison. Results : Age showed a significant negative correlation with fontanelle size (correlation coefficient -0.234, p < 0.05), indicating that fontanelle size decreases as infants age. No significant differences in fontanelle size were observed among the three CVA groups ( p = 0.074) or between the developmentally delayed and non-delayed groups ( p = 0.09). This study found no correlation between CVA and fontanelle size or between fontanelle size and developmental delay. Conclusions : The findings show that, while anterior fontanelle size decreased with age, there was no significant correlation between the fontanelle size and the severity of deformational plagiocephaly or developmental delays.

The liver has a unique ability to regenerate in response to injury or disease with hepatocytes and biliary epithelial cells (BECs) driving the regenerative response. Liver progenitor cells (LPCs) also play role in regeneration with the ability to differentiate into either hepatocytes or BECs. However, during chronic liver disease, the regenerative capacity of the liver is impaired. The use of LPCs is a promising therapeutic strategy for patients with chronic liver diseases. LPCs can be expanded in vitro as self-renewing organoids, however, most approaches to LPC organoids do not include critical cells from the LPC niche in 3D organoid cultures. In this study, we highlight the role of liver endothelial cells (LiECs), as a part of LPC niche, in supporting the hepatobiliary organoids in long-term culture even in the absence of defined growth supplements, such as Wnt agonists. Furthermore, LiECs alter the gene expression profile of hepatobiliary organoids involved in inflammation, migration, extracellular matrix organization, and receptor signaling pathway through paracrine manner. Our findings expand the role of LiECs for regulating stemness of LPCs and elucidate a role for niche cells in a LPC organoid co-culture model with a reduction in growth supplements., 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 The Authors.)

Background: To investigate the clinical treatment status, such as treatment regimen, bleeding events, and drug dose, in patients with hemophilia B in South Korea., Methods: In this retrospective chart review, data of patients with hemophilia B from eight university hospitals were collected. Demographic and clinical data, treatment data, such as regimen and number of injections, dose of factor IX concentrate, and bleeding data were reviewed. Descriptive analyses were performed with annual data for 2019, 2020, and 2021, as well as the three years consecutively., Results: The medical records of 150 patients with hemophilia B between January 1, 2019, and December 31, 2021, were collected. Among these, 72 (48.0%) were severe, 47 (31.3%) were moderate, and 28 (18.7%) were mild. The results showed approximately two times more patients receiving prophylaxis as those receiving on-demand therapy, with 66.1% of patients receiving prophylaxis in 2019, 64.9% in 2020, and 72.1% in 2021. Annualized bleeding rates were 2.2% (± 3.1) in 2019, 1.8% (± 3.0) in 2020, and 1.8% (± 2.9) in 2021 among patients receiving prophylaxis. For the doses of factor IX concentrate, patients receiving prophylaxis received an average of 41.6 (± 11.9) IU/Kg/Injection in 2019, 45.7 (± 12.9) IU/Kg/Injection in 2020, and 60.1 (± 24.0) IU/Kg/Injection in 2021., Conclusions: Clinically, prophylaxis is more prevalent than reported. Based on insights gained from current clinical evidence, it is expected that the unmet medical needs of patients can be identified, and physicians can evaluate the status of patients and actively manage hemophilia B using more effective treatment strategies., (© 2024. The Author(s).)

Background: Teenagers with epilepsy require special attention to ensure a successful treatment journey. Our objective was to delineate the clinical characteristics of adolescent-onset epilepsy (AOE) and investigate the predictive factors influencing first-year seizure freedom., Methods: We retrospectively analyzed the medical records of patients whose first seizure occurred between the ages of 10 and 19 years and who received antiseizure medication (ASM) treatment for at least 12 months., Results: A total of 67 patients were included, with an average age of 13.5 ± 2.3 years at the onset of their first seizure. The average follow-up period was 45.2 ± 16.9 months, and comorbid conditions were present in 23 patients (34.3%). The majority of the patient population (83.6%) was affected by generalized epilepsy. The most common epilepsy syndrome was epilepsy with generalized tonic-clonic seizures alone at 70.1% (juvenile myoclonic epilepsy 11.9%, juvenile absence epilepsy 1.5%). Regarding ASM treatment, 31 patients (46.3%) received monotherapy, and 28 (41.8%) received dual therapy. Five patients (7.5%) encountered issues related to medication adherence. First-year seizure freedom was observed in 42 patients (62.7%). In multivariate analysis, a negative family history of epilepsy (odds ratio 12.1, 95% confidence interval 1.27-115.44, p  = 0.030) was identified as a strong predictive factor of first-year seizure freedom, along with ASM monotherapy (odds ratio 3.99, 95% confidence interval 1.05-15.21, p  = 0.043)., Conclusion: These findings suggest that AOE typically exhibits effective control of seizures. A negative family history of epilepsy and ASM monotherapy emerges as robust predictor of achieving favorable outcomes within the early stage of treatment., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and Objectives: Localization of a sound source in the horizontal plane depends on the listener's interaural comparison of arrival time and level. Hearing loss (HL) can reduce access to these binaural cues, possibly disrupting the localization and memory of spatial information. Thus, this study aimed to investigate the horizontal sound localization performance and the spatial short-term memory in listeners with actual and simulated HL., Subjects and Methods: Seventeen listeners with bilateral symmetric HL and 17 listeners with normal hearing (NH) participated in the study. The hearing thresholds of NH listeners were elevated by a spectrally shaped masking noise for the simulations of unilateral hearing loss (UHL) and bilateral hearing loss (BHL). The localization accuracy and errors as well as the spatial short-term memory span were measured in the free field using a set of 11 loudspeakers arrayed over a 150° arc., Results: The localization abilities and spatial short-term memory span did not significantly differ between actual BHL listeners and BHL-simulated NH listeners. Overall, the localization performance with the UHL simulation was approximately twofold worse than that with the BHL simulation, and the hearing asymmetry led to a detrimental effect on spatial memory. The mean localization score as a function of stimulus location in the UHL simulation was less than 30% even for the front (0° azimuth) stimuli and much worse on the side closer to the simulated ear. In the UHL simulation, the localization responses were biased toward the side of the intact ear even when sounds were coming from the front., Conclusions: Hearing asymmetry induced by the UHL simulation substantially disrupted the localization performance and recall abilities of spatial positions encoded and stored in the memory, due to fewer chances to learn strategies to improve localization. The marked effect of hearing asymmetry on sound localization highlights the need for clinical assessments of spatial hearing in addition to conventional hearing tests.

This study compared the impact of spectral and temporal degradation on vocoded speech recognition between early-blind and sighted subjects. The participants included 25 early-blind subjects (30.32 ± 4.88 years; male:female, 14:11) and 25 age- and sex-matched sighted subjects. Tests included monosyllable recognition in noise at various signal-to-noise ratios (-18 to -4 dB), matrix sentence-in-noise recognition, and vocoded speech recognition with different numbers of channels (4, 8, 16, and 32) and temporal envelope cutoff frequencies (50 vs 500 Hz). Cortical-evoked potentials (N2 and P3b) were measured in response to spectrally and temporally degraded stimuli. The early-blind subjects displayed superior monosyllable and sentence recognition than sighted subjects (all p  < 0.01). In the vocoded speech recognition test, a three-way repeated-measure analysis of variance (two groups × four channels × two cutoff frequencies) revealed significant main effects of group, channel, and cutoff frequency (all p  < 0.001). Early-blind subjects showed increased sensitivity to spectral degradation for speech recognition, evident in the significant interaction between group and channel ( p  = 0.007). N2 responses in early-blind subjects exhibited shorter latency and greater amplitude in the 8-channel ( p  = 0.022 and 0.034, respectively) and shorter latency in the 16-channel ( p  = 0.049) compared with sighted subjects. In conclusion, early-blind subjects demonstrated speech recognition advantages over sighted subjects, even in the presence of spectral and temporal degradation. Spectral degradation had a greater impact on speech recognition in early-blind subjects, while the effect of temporal degradation was similar in both groups., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Choi et al.)

Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level is primarily used as a biomarker for left ventricular (LV) dysfunction. It is influenced by various conditions, such as myocardial strain and situations affecting the clearance of NT-proBNP, including sepsis and shock. In this study, we investigated the appropriateness of NT-proBNP as a prognostic factor for septic shock. Patients with septic shock who visited the emergency department of the Ewha Womans' University Mokdong Hospital between January 1, 2018, and December 31, 2020, were classified into the survival group (those who survived in the hospital and were discharged) and the death group (those who died in the hospital). The effectiveness of NT-proBNP, lactate, and blood urea nitrogen as predictive factors of in-hospital mortality was evaluated using the area under the receiver operating characteristic (AUROC) curve. The AUROC curve was 0.678 and 0.648 for lactate and NT-proBNP, respectively, with lactate showing the highest value. However, there was no significant difference between lactate and NT-proBNP levels in the comparison of their AUROC curve (p = 0.6278). NT-proBNP could be a useful predictor of in-hospital mortality in patients with septic shock who present to the emergency department., (© 2024. The Author(s).)

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring., Competing Interests: Competing interests statement:The authors declare no competing interest.

Intracranial arterial dolichoectasia (IADE) is associated with the interaction of hypertension and inflammation, and microcurrent can be effective in hypertension. Therefore, this study aimed to investigate the therapeutic effect of microcurrent electrical stimulation in a mouse IADE model. This study randomly categorized 20 mice into five groups: group 1-C (healthy control), group 2-D (IADE model), group 3-M + D (microcurrent administration before nephrectomy and until brain surgery), group 4-D + M (microcurrent administration for 4 weeks following brain surgery), and group 5-M (microcurrent administration for 4 weeks). Cerebral artery diameter and thickness and cerebral arterial wall extracellular matrix components were assessed. Among the five groups, group 2-D showed significantly higher cerebral arterial wall diameter (117.79 ± 17.05 µm) and proportion of collagen (42.46 ± 14.12%) and significantly lower arterial wall thickness (9.31 ± 2.26 µm) and proportion of smooth muscle cell (SMC) and elastin in the cerebral arterial wall (SMC: 38.05 ± 10.32%, elastin: 11.11 ± 6.97%). Additionally, group 4-D + M exhibited a non-significantly lower diameter (100.28 ± 25.99 µm) and higher thickness (12.82 ± 5.17 µm). Group 5-M demonstrated no evidence of toxicity in the liver and brain. The pilot study revealed that microcurrent is effective in preventing IADE development, although these beneficial effects warrant further investigation., (© 2024. The Author(s).)

In a recent stereotactic body radiation therapy animal model, radiation pneumonitis and radiation pulmonary fibrosis were observed at around 2 and 6 weeks, respectively. However, the molecular signature of this model remains unclear. This study aimed to examine the molecular characteristics at these two stages using RNA-seq analysis. Transcriptomic profiling revealed distinct transcriptional patterns for each stage. Inflammatory response and immune cell activation were involved in both stages. Cell cycle processes and response to type II interferons were observed during the inflammation stage. Extracellular matrix organization and immunoglobulin production were noted during the fibrosis stage. To investigate the impact of a 10 Gy difference on fibrosis progression, doses of 45, 55, and 65 Gy were tested. A dose of 65 Gy was selected and compared with 75 Gy. The 65 Gy dose induced inflammation and fibrosis as well as the 75 Gy dose, but with reduced lung damage, fewer inflammatory cells, and decreased collagen deposition, particularly during the inflammation stage. Transcriptomic analysis revealed significant overlap, but differences were observed and clarified in Gene Ontology and KEGG pathway analysis, potentially influenced by changes in interferon-gamma-mediated lipid metabolism. This suggests the suitability of 65 Gy for future preclinical basic and pharmaceutical research connected with radiation-induced lung injury.

Multiple myeloma (MM) is a hematological malignancy caused by malignant proliferation of plasma cells in bone marrow. Over the last decade, the survival outcome of patients with multiple myeloma (MM) has been substantially improved with the emergence of novel therapeutic agents. However, MM remains an incurable neoplastic plasma cell disorder. In addition, almost all MM patients inevitably relapse due to drug resistance. Chimeric antigen receptor (CAR)-modified NK cells represent a promising immunotherapeutic modality for cancer treatment. In this study, NK92 cells were engineered to express the third generation of BCMA CAR. In vitro, BCMA CAR-engineered NK92 cells displayed higher cytotoxicity and produced more cytokines such as IFN-γ and granzyme B than NK92 cells when they were co-cultured with MM cell lines. Furthermore, BCMA CAR-engineered NK92 cells released significantly higher amounts of cytokines and showed higher cytotoxicity when they were exposed to primary cells isolated from MM patients. The cytotoxicity of BCMA CAR NK92 cells was enhanced after MM cells were treated with bortezomib. Additionally, BCMA CAR NK92 cells exhibited potent antitumor activities in subcutaneous tumor models of MM. These results demonstrate that regional administration of BCMA CAR NK92 cells is a potentially promising strategy for treating MM.

Introduction: Alzheimer's disease (AD) poses an increasing global health challenge and is marked by gradual cognitive deterioration, memory impairment, and neuroinflammation. Innovative therapeutic approaches as non-pharmacological protocol are urgently needed with side effect risk of drugs. Microcurrent therapy, a non-invasive modality involving low-level electrical currents, has emerged as a potential solution to address AD's complex pathogenesis. This study investigates the optimal application of microcurrent therapy as a clinical protocol for AD, utilizing a comprehensive approach that integrates behavioral assessments and neuroinflammation evaluation in a mouse model of dementia., Methods and Results: The results reveal that microcurrent therapy holds promise in ameliorating memory impairment and reducing neuroinflammation in AD. Behavioral assessments, including the Novel Object Recognition Test (NOR) and Radial Arm Maze Test (RAM), demonstrated improved cognitive function following microcurrent therapy. Furthermore, microcurrent therapy inhibited expression of neuroinflammatory proteins, including ionized calcium binding adaptor molecule 1 (Iba1), and glial fibrillary acidic protein (GFAP) in current-treated group. Mechanistic insights suggest that microcurrent therapy may modulate neuroinflammation through the regulation of MAPK signaling pathways., Conclusion: This study emphasizes the prospect of microcurrent therapy as a safe and efficacious non-pharmacological strategy for Alzheimer's disease (AD), providing optimism to the countless individuals impacted by this debilitating ailment. These results contribute to the developments of an innovative clinical protocol for AD and recovery from neurological injury, underscoring the significance of investigating unconventional therapeutic approaches for addressing this complex condition., 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 © 2024 Kim, Lee, Lee and Kwon.)

As the global population ages, concerns regarding aesthetic appearance have increased. Wearable light-emitting diode (LED) devices have received significant attention in the cosmetic fields due to their non-invasive, non-thermal, home-use characteristics. However, conventional bulk LED chips have limitations in flexibility and uniform irradiation, hindering efficient light penetration into the skin. Here, we introduce a flexible, surface-lighting microLED (FSLED) patch with uniform light-emission for various skincare applications. The FSLED was fabricated using a pick-and-place transfer technique, which allows for high-density irradiation over the large area, while maintaining outstanding mechanical flexibility. In addition, the FSLED was designed to deliver light efficiently and emit light evenly by conforming to the skin. Finally, we prove the effect of the FSLED for pore tightening and skin rejuvenation through clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to determine whether the repair of a medial meniscus posterior root tear (MMPRT) is effective for MMPRT healing, cartilage regeneration, and clinical outcomes in opening wedge high tibial osteotomy (OWHTO)., Methods: This retrospective study included 80 patients who underwent OWHTO and subsequent second-look arthroscopy. The patients were divided into OWHTO-with-MMPRT-repair (n = 40) and OWHTO alone (n = 40) groups, and the healing rates (complete/partial/failure) were compared. Each group was further divided into over- and under-corrected subgroups to compare healing rates. The International Cartilage Repair Society (ICRS) grade, cartilage defect size, Koshino stage, ICRS cartilage repair assessment score of the medial femoral condyle (MFC), and International Knee Documentation Committee (IKDC) scores between the OWHTO-with-MMPRT-repair and OWHTO alone groups were compared according to whether microfracture was performed on the MFC., Results: The overall healing rate of the MMPRT was higher in the OWHTO-with-MMPRT-repair group than that in the OWHTO alone group (P < 0.001). In addition, in the subgroup analysis, no difference in the MMPRT healing rate between the over-correction and under-correction groups when MMPRT repair was performed (n.s). In contrast, without MMPRT repair, the healing rate was lower in the under-correction group than that in the over-correction group (P = 0.03). Cartilage regeneration of the OWHTO-with-MMPRT-repair group was superior to that of the OWHTO alone group (P < 0.05). The IKDC subjective scores of the OWHTO-with-MMPRT-repair and OWHTO alone groups were 34.5 and 33.1 before surgery (n.s) and 50 and 47.2 at one year after surgery, respectively (n.s). These differences between the two groups for cartilage regeneration and IKDC subjective scores showed the same pattern regardless of microfractures., Conclusions: MMPRT repair during OWHTO might improve MMPRT healing, even with under-correction, and cartilage regeneration of MFC, regardless of microfracture. However, OWHTO with MMPRT repair might not improve short-term clinical outcomes compared to OWHTO alone. Further randomized clinical trials are necessary., Level of Evidence: III, Retrospective cohort study., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Transfer printing of inorganic thin-film semiconductors has attracted considerable attention to realize high-performance soft electronics on unusual substrates. However, conventional transfer technologies including elastomeric transfer printing, laser-assisted transfer, and electrostatic transfer still have challenging issues such as stamp reusability, additional adhesives, and device damage. Here, a micro-vacuum assisted selective transfer is reported to assemble micro-sized inorganic semiconductors onto unconventional substrates. 20 μm-sized micro-hole arrays are formed via laser-induced etching technology on a glass substrate. The vacuum controllable module, consisting of a laser-drilled glass and hard-polydimethylsiloxane micro-channels, enables selective modulation of micro-vacuum suction force on microchip arrays. Ultrahigh adhesion switchability of 3.364 × 10 6 , accomplished by pressure control during the micro-vacuum transfer procedure, facilitates the pick-up and release of thin-film semiconductors without additional adhesives and chip damage. Heterogeneous integration of III-V materials and silicon is demonstrated by assembling microchips with diverse shapes and sizes from different mother wafers on the same plane. Multiple selective transfers are implemented by independent pressure control of two separate vacuum channels with a high transfer yield of 98.06%. Finally, flexible micro light-emitting diodes and transistors with uniform electrical/optical properties are fabricated via micro-vacuum assisted selective transfer., (© 2023. The Author(s).)

Radiation-induced lung fibrosis (RILF) is a common complication of radiotherapy in lung cancer. However, to date no effective treatment has been developed for this condition. NXC736 is a novel small-molecule compound that inhibits NLRP3, but its effect on RILF is unknown. NLRP3 activation is an important trigger for the development of RILF. Thus, we aimed to evaluate the therapeutic effect of NXC736 on lung fibrosis inhibition using a RILF animal model and to elucidate its molecular signaling pathway. The left lungs of mice were irradiated with a single dose of 75 Gy. We observed that NXC736 treatment inhibited collagen deposition and inflammatory cell infiltration in irradiated mouse lung tissues. The damaged lung volume, evaluated by magnetic resonance imaging, was lower in NXC736-treated mice than in irradiated mice. NXC736-treated mice exhibited significant changes in lung function parameters. NXC736 inhibited inflammasome activation by interfering with the NLRP3-ASC-cleaved caspase-1 interaction, thereby reducing the expression of IL-1β and blocking the fibrotic pathway. In addition, NXC736 treatment reduced the expression of epithelial-mesenchymal transition markers such as α-SMA, vimentin, and twist by blocking the Smad 2,3,4 signaling pathway. These data suggested that NXC736 is a potent therapeutic agent against RILF.

Among the various thermal stress indices, apparent temperature (AT) is closely related to public health indicators, and consequently is widely used by weather agencies around the world. Therefore, in this paper we estimate the changes in AT and contributing components in Korea as a whole and in five major cities (Seoul, Gwanju, Daegu, Daejeon, and Busan) using national standard climate scenarios based on the coupled model inter-comparison project (CMIP6). In the present day, high AT occurs in major cities due to high temperature (TAS) and relative humidity (RH). Our findings reveal that even when TAS is relatively low, large AT occurs with higher humidity. Notably, in future warmer climate conditions, high AT may first appear in the five major cities and then extend to the surrounding areas. An increase in TAS and RH during the pre-hot season (March to June) may lead to earlier occurrence of thermal risks in future warmer climate conditions and more frequent occurrence of high thermal stress events. Our study can serve as a reference for future information on thermal risk changes in Korea. Considering those who have not adapted to high temperature environments, our findings imply that thermal risks will become more serious and that heat adaptation strategies will be needed during the pre-hot season under future warmer climate conditions.

Porous 2D materials with high conductivity and large surface area have been proposed for potential electromagnetic interference (EMI) shielding materials in future mobility and wearable applications to prevent signal noise, transmission inaccuracy, system malfunction, and health hazards. Here, we report on the synthesis of lightweight and flexible flash-induced porous graphene (FPG) with excellent EMI shielding performance. The broad spectrum of pulsed flashlight induces photo-chemical and photo-thermal reactions in polyimide films, forming 5 × 10 cm 2 -size porous graphene with a hollow pillar structure in a few milliseconds. The resulting material demonstrated low density (0.0354 g cm -3 ) and outstanding absolute EMI shielding effectiveness of 1.12 × 10 5  dB cm 2  g -1 . The FPG was characterized via thorough material analyses, and its mechanical durability and flexibility were confirmed by a bending cycle test. Finally, the FPG was utilized in drone and wearable applications, showing effective EMI shielding performance for internal/external EMI in a drone radar system and reducing the specific absorption rate in the human body., (© 2023. The Author(s).)

Genetically engineered fusion polypeptides have been investigated to introduce unique bio-functionality and improve some therapeutic activity for anti-angiogenesis. We report herein that stimuli-responsive, vascular endothelial growth factor receptor 1 (VEGFR1) targeting fusion polypeptides composed of a VEGFR1 (fms-like tyrosine kinase-1 (Flt1)) antagonist, an anti-Flt1 peptide, and a thermally responsive elastin-based polypeptide (EBP) were rationally designed at the genetic level, biosynthesized, and purified by inverse transition cycling to develop potential anti-angiogenic fusion polypeptides to treat neovascular diseases. A series of hydrophilic EBPs with different block lengths were fused with an anti-Flt1 peptide, forming anti-Flt1-EBPs, and the effect of EBP block length on their physicochemical properties was examined. While the anti-Flt1 peptide decreased phase-transition temperatures of anti-Flt1-EBPs, compared with EBP blocks, anti-Flt1-EBPs were soluble under physiological conditions. The anti-Flt1-EBPs dose dependently inhibited the binding of VEGFR1 against vascular endothelial growth factor (VEGF) as well as tube-like network formation of human umbilical vein endothelial cells under VEGF-triggered angiogenesis in vitro because of the specific binding between anti-Flt1-EBPs and VEGFR1. Furthermore, the anti-Flt1-EBPs suppressed laser-induced choroidal neovascularization in a wet age-related macular degeneration mouse model in vivo. Our results indicate that anti-Flt1-EBPs as VEGFR1-targeting fusion polypeptides have great potential for efficacious anti-angiogenesis to treat retinal-, corneal-, and choroidal neovascularization.

Background: Since the onset of the coronavirus disease 2019 pandemic, virtual simulation has emerged as an alternative to traditional teaching methods as it can be employed within the recently established contact-minimizing guidelines. This prospective education study aimed to develop a virtual reality simulator for a lumbar transforaminal epidural block (LTFEB) and demonstrate its efficacy., Methods: We developed a virtual reality simulator using patient image data processing, virtual X-ray generation, spatial registration, and virtual reality technology. For a realistic virtual environment, a procedure room, surgical table, C-arm, and monitor were created. Using the virtual C-arm, the X-ray images of the patient's anatomy, the needle, and indicator were obtained in real-time. After the simulation, the trainees could receive feedback by adjusting the visibility of structures such as skin and bones. The training of LTFEB using the simulator was evaluated using 20 inexperienced trainees. The trainees' procedural time, rating score, number of C-arm taken, and overall satisfaction were recorded as primary outcomes., Results: The group using the simulator showed a higher global rating score (P = 0.014), reduced procedural time (P = 0.025), reduced number of C-arm uses (P = 0.001), and higher overall satisfaction score (P = 0.007)., Conclusions: We created an accessible and effective virtual reality simulator that can be used to teach inexperienced trainees LTFEB without radiation exposure. The results of this study indicate that the proposed simulator will prove to be a useful aid for teaching LTFEB.

Wearable blood-pressure sensors have recently attracted attention as healthcare devices for continuous non-invasive arterial pressure (CNAP) monitoring. However, the accuracy of wearable blood-pressure (BP) monitoring devices has been controversial due to the low signal quality of sensors, the absence of an accurate transfer function to convert the sensor signals into BP values, and the lack of clinical validation regarding measurement precision. Here, a wearable piezoelectric blood-pressure sensor (WPBPS) is reported, which achieves a high normalized sensitivity (0.062 kPa -1 ), and fast response time (23 ms) for CNAP monitoring. The transfer function of a linear regression model is designed, offering a simple solution to convert the flexible piezoelectric sensor signals into BP values. In order to verify the measurement accuracy of WPBPS, clinical trials are performed on 35 subjects aged from 20 to 80 s after screening. The mean difference between the WPBPS and a commercial sphygmomanometer of 175 BP data pairs is -0.89 ± 6.19 and -0.32 ± 5.28 mmHg for systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively. By building a WPBPS-embedded wristwatch, the potentially promising use of a convenient, portable, continuous BP monitoring system for cardiovascular disease diagnosis is demonstrated., (© 2023 Wiley-VCH GmbH.)

Purpose: Multiple studies have attempted to demonstrate the benefits of augmented reality (AR)-assisted navigation systems in surgery. Lumbosacral transforaminal epidural injection is an effective treatment commonly used in patients with radiculopathy due to spinal degenerative pathologies. However, few studies have applied AR-assisted navigation systems to this procedure. The study aimed to investigate the safety and effectiveness of an AR-assisted navigation system for transforaminal epidural injection., Patients and Methods: Through a real-time tracking system and a wireless network to the head-mounted display, computed tomography images of the spine and the path of a spinal needle to the target were visualized on a torso phantom with respiration movements installed. From L1/L2 to L5/S1, needle insertions were performed using an AR-assisted system on the left side of the phantom, and the conventional method was performed on the right side., Results: The procedure duration was approximately three times shorter, and the number of radiographs required was reduced in the experimental group compared to the control group. The distance from the needle tips to the target areas in the plan showed no significant difference between the two groups. (AR group 1.7 ± 2.3mm, control group 3.2 ± 2.8mm, P value 0.067)., Conclusion: An AR-assisted navigation system may be used to reduce the time required for spinal interventions and ensure the safety of patients and physicians in view of radiation exposure. Further studies are essential to apply AR-assisted navigation systems to spine interventions., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Jun et al.)

Incorporating stimuli-responsive block copolymers to hierarchical metallic nanoparticles (MNPs) is of particular interest due to their tunable plasmonic properties responding to environmental stimuli. We herein report thermo-responsive plasmonic core-satellite hybrid nanostructures with tunable nanogaps as surface-enhanced Raman scattering (SERS) nanotags. Two different diblock copolymers with opposite charges, poly(acrylic acid- b-N -isopropylacrylamide) (p(AAc- b -NIPAM)) and poly( N , N -dimethylaminoethyl methacrylate- b-N -isopropylacrylamide) (p(DMAEMA- b -NIPAM)), were synthesized. The negatively charged p(AAc- b -NIPAM)s were bound to gold nanospheres (GNSs), while the positively charged p(DMAEMA- b -NIPAM)s were conjugated to gold nanorods (GNRs) via gold-sulfur bonds. When p(AAc- b -NIPAM)-GNSs and p(DMAEMA- b -NIPAM)-GNRs were electrostatically complexed, plasmonic hybrid nanostructures consisting of both GNS satellites and a GNR core were formed. Dynamic tuning of electromagnetic coupling of their nanogaps was achieved via a temperature-triggered conformational change of p(NIPAM) blocks. Furthermore, a sandwich-type immunoassay for the detection of immunoglobulin G was performed to demonstrate these core-satellites as potential SERS nanotags. Our results showed that these plasmonic core-satellites with stimuli-responsiveness are promising for SERS-based biosensing applications.

Metastatic colorectal cancer (CRC) remains a substantial problem for mortality and requires screening and early detection efforts to increase survival. Epithelial-mesenchymal transition (EMT) and circulation of tumor cells in the blood play important roles in metastasis. To identify a novel target for metastasis of CRC, we conducted a gene microarray analysis using extracted RNA from the blood of preclinical models. We found that NCK-associated protein 1 (NCKAP1) was significantly increased in the blood RNA of patient-derived xenograft (PDX) models of colon cancer. In the NCKAP1 gene knockdown-induced human colon cancer cell lines HCT116 and HT29, there was a reduced wound healing area and significant inhibition of migration and invasion. As the result of marker screening for cytoskeleton and cellular interactions, CRC treated with siRNA of NCKAP1 exhibited significant induction of CDH1 and phalloidin expression, which indicates enhanced adherent cell junctions and cytoskeleton. In HCT116 cells with a mesenchymal state induced by TGFβ1, metastasis was inhibited by NCKAP1 gene knockdown through the inhibition of migration, and there was increased CTNNB1 expression and decreased FN expression. We established metastasis models for colon cancer to liver transition by intrasplenic injection shRNA of NCKAP1-transfected HCT116 cells or by implanting tumor tissue generated with the cells on cecal pouch. In metastasis xenograft models, tumor growth and liver metastasis were markedly reduced. Taken together, these data demonstrate that NCKAP1 is a novel gene regulating EMT that can contribute to developing a diagnostic marker for the progression of metastasis and new therapeutics for metastatic CRC treatment., (© 2023. The Author(s).)

Wearable light-emitting diode (LED)-based phototherapeutic devices have recently attracted attention as skin care tools for wrinkles, acne, and hyperpigmentation. However, the therapeutic effectiveness and safety of LED stimulators are still controversial due to their inefficient light transfer, high heat generation, and non-uniform spot irradiation. Here, a wearable surface-lighting micro-LED (SµLED) photostimulator is reported for skin care and cosmetic applications. The SµLEDs, consisting of a light diffusion layer (LDL), 900 thin film µLEDs, and polydimethylsiloxane (PDMS), achieve uniform surface-lighting in 2 × 2 cm 2 -sized area with 100% emission yields. The SµLEDs maximize photostimulation effectiveness on the skin surface by uniform irradiation, high flexibility, and thermal stability. The SµLED's effect on melanogenesis inhibition is evaluated via in vitro and in vivo experiments to human skin equivalents (HSEs) and mouse dorsal skin, respectively. The anti-melanogenic effect of SµLEDs is confirmed by significantly reduced levels of melanin contents, melan-A, tyrosinase, and microphthalmia-associated transcription factor (MITF), compared to a conventional LED (CLED) stimulator., (© 2022 Wiley-VCH GmbH.)

A cognitive agent performing in the real world needs to learn relevant concepts about its environment (e.g., objects, color, and shapes) and react accordingly. In addition to learning the concepts, it needs to learn relations between the concepts, in particular spatial relations between objects. In this paper, we propose three approaches that allow a cognitive agent to learn spatial relations. First, using an embodied model, the agent learns to reach toward an object based on simple instructions involving left-right relations. Since the level of realism and its complexity does not permit large-scale and diverse experiences in this approach, we devise as a second approach a simple visual dataset for geometric feature learning and show that recent reasoning models can learn directional relations in different frames of reference. Yet, embodied and simple simulation approaches together still do not provide sufficient experiences. To close this gap, we thirdly propose utilizing knowledge bases for disembodied spatial relation reasoning. Since the three approaches (i.e., embodied learning, learning from simple visual data, and use of knowledge bases) are complementary, we conceptualize a cognitive architecture that combines these approaches in the context of spatial relation learning., 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 © 2022 Lee, Yao, Özdemir, Li, Weber, Liu and Wermter.)

The East Asian summer monsoon (EASM) is an influential monsoon system that provides two-thirds of the annual precipitation in the Asian region. Therefore, considerable attention has been paid to the changes in future climate. Thus far, studies on EASM characteristics have not been conducted considering specific global warming level (GWL) using Coupled Model Inter-comparison Project 6 (CMIP6) simulations. We analyze the EASM characteristics in present-day (PD) and the changes in EASM corresponding to the projections at 1.5, 2.0, and 3.0°C GWLs. The newly released 30 CMIP6 models effectively captured the migration of the monsoon in PD with a pattern correlation coefficient of 0.91, which is an improvement over that reported in previous studies. As a result of the separate analysis of the P1 (first primary peak; 33-41 pentad) and P2 (from P1 to the withdrawal; 42-50 pentad) periods, a higher frequency of weak to moderate precipitation in P2 and a smaller amount of moderate to extreme precipitation in P1 are mainly occurred. The CMIP6 models project increasing precipitation of approximately 5.7%°C-1, 4.0%°C-1, and 3.9%°C-1 for the three GWLs, respectively, with longer durations (earlier onset and delayed termination). Under the three GWLs, the projected precipitation frequency decreases below 6 mm d-1 (76th percentile) and significant increases above 29 mm d-1 (97th percentile). These changes in precipitation frequency are associated with an increasing distribution of precipitation amount above 97th percentile. Additionally, these tendencies in P1 and P2 are similar to that of the total period, while the maximum changes occur in 3.0°C GWL. In particular, future changes in EASM accelerate with continuous warming and are mainly affected by enhanced extreme precipitation (above 97th percentile). Our findings are expected to provide information for the implementation of sustainable water management programs as a part of national climate policy., Competing Interests: The authors have declared that no competing interests exist.

A variety of block copolypeptides with stimuli responsiveness have been of growing interest for dynamic self-assembly. Here, multistimuli-responsive triblock copolypeptides composed of thermosensitive elastin-based polypeptides (EBP) and ligand-responsive calmodulin (CalM) were genetically engineered, over-expressed, and nonchromatographically purified by inverse transition cycling. Diluted EBP-CalM-EBP (ECE) triblock copolypeptides under physiological conditions self-assembled into vesicles at the nanoscale by temperature-triggered aggregation of the EBP block with lower critical solution temperature behaviors. Furthermore, concentrated ECE triblock copolypeptides under identical conditions exhibited thermally induced gelation, resulting in physically crosslinked hydrogels. They showed controlled rheological and mechanical properties depending on the conformational change of the CalM middle block induced by binding either Ca 2+ or Ca 2+ and trifluoperazines (TFPs) as ligands. In addition, both Ca 2+ -free and Ca 2+ -bound ECE triblock copolypeptide hydrogels exhibited biocompatibility, while those bound to both Ca 2+ and TFPs showed severe cytotoxicity because of controlled TFP release of the CalM blocks. The ECE triblock hydrogels with stimuli responsiveness would be useful as injectable drug delivery depots for biomedical applications.

Lung inflammation and fibrosis are common side effects of radiotherapy that can lead to serious reduction in the quality of life of patients. However, no effective treatment is available, and the mechanisms underlying its pathophysiology are poorly understood. Irradiation increases formyl peptide receptor 2 (FPR2) expression in lung tissue, and FPR2 agonists are known to promote the uptake of apoptosis cells, referred to as efferocytosis that is a hallmark of the resolution of inflammation. Herein, in a mouse model of radiation-induced lung injury (RILI), efferocytosis was induced by injecting apoptotic cells into the lung through the trachea, and its correlation with FPR expression and the effect of efferocytosis and FPR expression on RILI were assessed. Interestingly, when apoptotic cells were injected into the lung, the radiation-induced increase in FPR2 expression was further amplified. In the mouse model of RILI, apoptotic cell instillation reduced the volume of the damaged lung and prevented the decrease in lung function. Additionally, the expression of inflammatory cytokines, fibrosis-related markers, and oxidative stress-related markers was reduced by apoptotic cell instillation. Co-administration of apoptotic Jurkat cells and WRW4, the FPR2 antagonist, reversed these effects. These findings suggest that efferocytosis induced by apoptotic cell instillation and enhanced FPR2 expression attenuate RILI, thereby alleviating lung inflammation and fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Backgrounds: South Korea, a nation with rapidly aging population, has the highest suicide rates in the world, and the elderly have a suicide rate three times higher than the national average. We classified the drugs ingested for suicide attempts by age groups and compare the clinical outcomes between non-elderly and elderly patients who attempted suicide by ingesting drugs., Materials and Methods: Data were obtained from the nationwide Emergency Department-Based Injury Surveillance of the Korea Centers for Disease Control and Prevention, South Korea between January 2011 and December 2016., Results: There were 12,104 patients who attempted suicide by ingesting drugs, of whom the elderly (73.5%) ingested more sedatives and hypnotics than the non-elderly (53.9%); of these drugs, zolpidem ingestion was higher in the elderly than the non-elderly. Conversely, the non-elderly ingested more antipsychotics and antidepressants (15.9%) and analgesics (10.8%) than the elderly (7.4% and 2.8%, respectively). The elderly had longer hospital stay, higher intensive care unit (ICU) admission rate, and higher mortality rate than the non-elderly: more elderly patients (30.2%) were admitted to the ICU than the non-elderly (15.7%); the duration of hospital stays was 6.27 ± 11.35 days in the elderly and 8.94 ± 14.85 days in the non-elderly; and the mortality rate was 0.4% in the non-elderly and 3.0% in the elderly., Conclusion: Findings suggest that zolpidem has become the greatest risk factor for the elderly Koreans in suicide attempts. Further prevention efforts are needed to prevent suicide among the elderly.

Background: Next-generation sequencing (NGS) has been implemented as a rapid and cost-effective BRCA1/2 test strategy. The Oncomine™ BRCA Research Assay is an NGS-based tool for simultaneous detection of small-scale mutations and large genomic rearrangements (LGRs). We evaluated this NGS assay using different versions of Ion Reporter™ (IR) software., Methods: A total of 258 patients with breast, ovarian, primary peritoneal, and fallopian tube cancer, or a family history thereof, were enrolled in the study. The NGS assay was implemented for all samples, and the results were compared with those of Sanger sequencing and MLPA., Results: All small-scale variations in Sanger sequencing were successfully detected by NGS assay. For the detection of LGRs, this assay showed 100% sensitivity from IR v5.10, and the latest version of the software (v5.16) showed the highest sensitivity and specificity., Conclusions: NGS with an appropriately updated workflow proved reliable for comprehensive BRCA1/2 gene testing, including LGR screening, which could facilitate efficient and accurate decision-making regarding treatment.

Background: Early and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to prevent spread of the infection. Understanding of the antibody response to SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19) is insufficient, particularly in relation to those whose responses persist for more than 1 month after the onset of symptoms. We conducted a SARS-CoV-2 antibody test to identify factors affecting the serological response and to evaluate its diagnostic utility in patients with COVID-19., Methods and Finding: We collected 1,048 residual serum samples from 396 patients with COVID-19 confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2. The samples had been used for routine admission tests in six healthcare institutions in Daegu. Antibody to SARS-CoV-2 was analyzed and the cutoff index (COI) was calculated for quantitative analysis. The patients' information was reviewed to evaluate the relationship between antibody positivity and clinical characteristics. The anti-SARS-CoV-2 antibody positivity rate was 85% and the average COI was 24·3. The positivity rate and COI increased with time elapsed since symptom onset. Anti-SARS-CoV-2 antibody persisted for at least 13 weeks after symptom onset at a high COI. There was a significant difference in anti-SARS-CoV-2 antibody positivity rate between patients with and without symptoms, but not according to sex or disease course. The descending COI pattern at weeks 1 to 5 after symptom onset was significantly more frequent in patients who died than in those who recovered., Conclusions: Anti-SARS-CoV-2 antibody persisted for at least 13 weeks at a high COI in patients with COVID-19. A decreasing COI pattern up to fifth week may be associated with a poor prognosis of COVID-19. As new treatments and vaccines are introduced, it is important to monitor continuously the usefulness of anti-SARS-CoV-2 antibody assays., Competing Interests: The authors have declared that no competing interests exist.

Background: Laboratory parameter abnormalities are commonly observed in COVID-19 patients; however, their clinical significance remains controversial. We assessed the prevalence, characteristics, and clinical impact of laboratory parameters in COVID-19 patients hospitalized in Daegu, Korea., Methods: We investigated the clinical and laboratory parameters of 1,952 COVID-19 patients on admission in nine hospitals in Daegu, Korea. The average patient age was 58.1 years, and 700 (35.9%) patients were men. The patients were classified into mild (N=1,612), moderate (N=294), and severe (N=46) disease groups based on clinical severity scores. We used chi-square test, multiple comparison analysis, and multinomial logistic regression to evaluate the correlation between laboratory parameters and disease severity., Results: Laboratory parameters on admission in the three disease groups were significantly different in terms of hematologic (Hb, Hct, white blood cell count, lymphocyte%, and platelet count), coagulation (prothrombin time and activated partial thromboplastin time), biochemical (albumin, aspartate aminotransferase, alanine aminotransferase, lactate, blood urea nitrogen, creatinine, and electrolytes), inflammatory (C-reactive protein and procalcitonin), cardiac (creatinine kinase MB isoenzyme and troponin I), and molecular virologic (Ct value of SARS-CoV-2 RdRP gene) parameters. Relative lymphopenia, prothrombin time prolongation, and hypoalbuminemia were significant indicators of COVID-19 severity. Patients with both hypoalbuminemia and lymphopenia had a higher risk of severe COVID-19., Conclusions: Laboratory parameter abnormalities on admission are common, are significantly associated with clinical severity, and can serve as independent predictors of COVID-19 severity. Monitoring the laboratory parameters, including albumin and lymphocyte count, is crucial for timely treatment of COVID-19.

Background: The Alcohol Use Disorder Identification Test (AUDIT) is widely used and validated in primary care settings for alcohol screening, yet practical challenges in conducting it in crowded clinics exist. Recently, a new abbreviated version of the AUDIT, was presented: the Screening Test for At-risk Drinking (STAD). This study aimed to evaluate the performance of STAD compared to other abbreviated versions of AUDIT for patients visiting the emergency department (ED)., Methods: This cross-sectional survey was conducted with 543 patients in the urban tertiary academic hospital ED in South Korea We diagnosed at-risk drinking using the entire AUDIT score. The optimal cut-off values, sensitivity, specificity, and the area under the receiver operating characteristics (AUROC) of the STAD were analyzed. We compared the AUROC with AUDIT-C and AUDIT-QF, which are previously abbreviated versions of AUDIT., Results: For males, the optimal cut-off value in the STAD test was 3 points with 83.1% sensitivity (95% CI: 75.3-89.2) and 95.9% specificity (95% CI: 91.2-98.5). For females, the optimal cut-off value was 2 points with 95.9% sensitivity (95% CI: 88.5-99.1) and 89.1% specificity (95% CI: 83.9-93.0). The AUROC curves for STAD were 0.964 (95% CI: 0.934-0.983) for males and 0.980 (95% CI: 0.965-0.993) for females., Conclusions: The STAD is a simple and useful test to screen at-risk drinking in the ED, and its assisted applications will enable faster and more efficient screening and management of at-risk drinking., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Auditory selective attention is a crucial top-down cognitive mechanism for understanding speech in noise. Cochlear implant (CI) users display great variability in speech-in-noise performance that is not easily explained by peripheral auditory profile or demographic factors. Thus, it is imperative to understand if auditory cognitive processes such as selective attention explain such variability. The presented study directly addressed this question by quantifying attentional modulation of cortical auditory responses during an attention task and comparing its individual differences with speech-in-noise performance. In our attention experiment, participants with CI were given a pre-stimulus visual cue that directed their attention to either of two speech streams and were asked to select a deviant syllable in the target stream. The two speech streams consisted of the female voice saying "Up" five times every 800 ms and the male voice saying "Down" four times every 1 s. The onset of each syllable elicited distinct event-related potentials (ERPs). At each syllable onset, the difference in the amplitudes of ERPs between the two attentional conditions (attended - ignored) was computed. This ERP amplitude difference served as a proxy for attentional modulation strength. Our group-level analysis showed that the amplitude of ERPs was greater when the syllable was attended than ignored, exhibiting that attention modulated cortical auditory responses. Moreover, the strength of attentional modulation showed a significant correlation with speech-in-noise performance. These results suggest that the attentional modulation of cortical auditory responses may provide a neural marker for predicting CI users' success in clinical tests of speech-in-noise listening.

Objective: This study aims to understand borderline personality disorder (BPD) features by employing the Personality Psychopathology Five (PSY-5) scales from the Minnesota Multiphasic Personality Inventory-2 (MMPI-2)., Methods: A total of 156 psychiatric patients completed PSY-5 scales of MMPI-2 and Personality Assessment Inventory-Borderline Subscale (PAI-BOR). Pearson's partial correlation analysis was conducted to control the impact of age and gender and to determine the relationship between PSY-5 scales and BOR. A hierarchical multiple regression analysis was implemented to examine whether PSY-5 scales predicted the BOR-total, and a path analysis was performed to determine whether PSY-5 scales predicted each PAI-BOR subscale., Results: The BOR-total score had a significant correlation with all PSY-5 scores, even after controlling for age and gender. However, only aggressiveness (AGGR), disconstraint (DISC), negative emotionality/neuroticism (NEGE), and introversion/low positive emotionality (INTR), excluding psychoticism (PSYC), significantly predicted BOR-total. The path analysis indicates that PSYC did not predict any BOR subscale, while NEGE predicted all BOR subscales., Conclusion: The study findings indicate that NEGE best reflects BPD features, while PSYC is far from the core domain that describes BPD. In addition, the influence of age should be considered when understanding BPD, since age predicted the BOR-total and two BOR subscales.

Purpose: There are few reports on the therapeutic effects of gonadotropin-releasing hormone agonists in boys with central precocious puberty, and studies reported in Korea are very rare. We aimed to assess the significance of clinical factors and the effects of gonadotropin-releasing hormone agonist treatment on final adult height in boys diagnosed with central precocious puberty., Methods: We retrospectively evaluated the medical records of 18 boys treated for idiopathic central precocious puberty between 2007 and 2018 at Chosun University Hospital. Gestational age, birth weight, and parental height were assessed at the initial visit. Chronological age, bone age, bone age/chronological age ratio, height and height standard deviation scores, predicted adult height, body mass index, and hormone levels were assessed during the treatment period., Results: At the time of diagnosis, the chronological age was 9.9±0.6 years, the bone age was 11.6±1.0 years, and the bone age/chronological age ratio was 1.20±0.1. The bone age/chronological age ratio decreased significantly to 1.12±0.1 at the end of treatment (P<0.05). The luteinizing hormone/follicular stimulating hormone ratios were 3.4±1.2, 0.6±0.4, and 0.6±1.0 at the start of treatment, after 1 year of treatment, and at the end of treatment, respectively. After gonadotropin-releasing hormone agonist treatment, the final adult height reached 172.0±4.8 cm compared to the target height range of 171.0±4.0 cm., Conclusion: In boys with central precocious puberty, gonadotropin-releasing hormone agonist treatment improved growth potential.

Background: Viral load and shedding duration are highly associated with the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, limited studies have reported on viral load or shedding in children and adolescents infected with sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Purpose: This study aimed to investigate the natural course of viral load in asymptomatic or mild pediatric cases., Methods: Thirty-one children (<18 years) with confirmed SARS-CoV-2 infection were hospitalized and enrolled in this study. Viral loads were evaluated in nasopharyngeal swab samples using real-time reverse transcription polymerase chain reaction (E, RdRp, N genes). cycle threshold (Ct) values were measured when patients met the clinical criteria to be released from quarantine., Results: The mean age of the patients was 9.8 years, 18 (58%) had mild disease, and 13 (42%) were asymptomatic. Most children were infected by adult family members, most commonly by their mothers. The most common symptoms were fever and sputum (26%), followed by cough and runny nose. Nine patients (29%) had a high or intermediate viral load (Ct value≤30) when they had no clinical symptoms. Viral load showed no difference between symptomatic and asymptomatic patients. Viral rebounds were found in 15 cases (48%), which contributed to prolonged viral detection. The mean duration of viral detection was 25.6 days. Viral loads were significantly lower in patients with viral rebounds than in those with no rebound (E, P=0.003; RdRp, P=0.01; N, P=0.02)., Conclusion: Our study showed that many pediatric patients with coronavirus disease 2019 (COVID-19) experienced viral rebound and showed viral detection for more than 3 weeks. Further studies are needed to investigate the relationship between viral rebound and infectiousness in COVID-19.

DNA-dependent protein kinase (DNA-PK), an essential component of the non-homologous end-joining (NHEJ) repair pathway, plays an important role in DNA damage repair (DDR). Therefore, DNA-PK inhibition is a promising approach for overcoming radiotherapy or chemotherapy resistance in cancers. In this study, we demonstrated that BR101801, a potent DNA-PK inhibitor, acted as an effective radiosensitizer in various human solid cancer cells and an in vivo xenograft model. Overall, BR101801 strongly elevated ionizing radiation (IR)-induced genomic instability via induction of cell cycle G 2 /M arrest, autophagic cell death, and impairment of DDR pathway in human solid cancer cells. Interestingly, BR101801 inhibited not only phosphorylation of DNA-PK catalytic subunit in NHEJ factors but also BRCA2 protein level in homologous recombination (HR) factors. In addition, combination BR101801 and IR suppressed tumor growth compared with IR alone by reducing phosphorylation of DNA-PK in human solid cancer xenografts. Our findings suggested that BR101801 is a selective DNA-PK inhibitor with a synergistic radiosensitizing effect in human solid cancers, providing evidence for clinical applications., Competing Interests: None., (AJCR Copyright © 2021.)

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started to spread in Daegu beginning at the end of February 2020. IgG and IgM antibodies against SARS-CoV-2 were measured in hospitalized patients with COVID-19 with moderate to severe symptoms to improve the understanding of antibody responses., Methods: We enrolled 312 patients with COVID-19 admitted to seven hospitals located in Daegu. Using serum (or plasma) samples from patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infections, both IgG and IgM antibodies were measured using commercial enzyme-linked immunosorbent assay (R-FIND CO¬VID-19 ELISA, SG medical, Seoul, Korea)., Results: The median value from the initial diagnosis, confirmed by SARS-CoV-2 PCR, to the sampling date was 24 days (day 1 to 88). The total positive rate of IgG was 93.9% and the positive IgM rate was 39.4%, without considering the elapsed period after diagnosis. Positive IgG and IgM rates were highest at 100.0% and 59.0%, respectively, at 3 weeks (15 - 21 days). IgG showed a high positive rate of 79.3% even within 7 days after the initial diag-nosis of the disease and maintained a positive rate of 97.8% until after 8 weeks., Conclusions: Among hospitalized patients with COVID-19, IgG was detected from the beginning of the diagnosis and persisted for an extended time period.

Background: Emergency departments (EDs) generally receive many casualties in disaster or mass casualty incidents (MCI). Some studies have conceptually suggested the surge capacity that ED should have; however, only few studies have investigated measurable numbers in one community. This study investigated the surge capacity of the specific number of accommodatable patients and overall preparedness at EDs in a metropolitan city., Methods: This cross-sectional study officially surveyed surge capacity and disaster preparedness for all regional and local emergency medical centers (EMC) in Seoul with the Seoul Metropolitan Government's public health division. This study developed survey items on space, staff, stuff, and systems, which are essential elements of surge capacity. The number of patients acceptable for each ED was investigated by triage level in ordinary and crisis situations. Multivariate linear regression analysis was performed on hospital resource variables related to surge capacity., Results: In the second half of 2018, a survey was conducted targeting 31 EMC directors in Seoul. It was found that all regional and local EMCs in Seoul can accommodate 848 emergency patients and 537 non-emergency patients in crisis conditions. In ordinary situations, one EMC could accommodate an average of 1.3 patients with Korean Triage and Acuity Scale (KTAS) level 1, 3.1 patients with KTAS level 2, and 5.7 patients with KTAS level 3. In situations of crisis, this number increased to 3.4, 7.8, and 16.2, respectively. There are significant differences in surge capacity between ordinary and crisis conditions. The difference in surge capacity between regional and local EMC was not significant. In both ordinary and crisis conditions, only the total number of hospital beds were significantly associated with surge capacity., Conclusion: If the hospital's emergency transport system is ideally accomplished, patients arising from average MCI can be accommodated in Seoul. However, in a huge disaster, it may be challenging to handle the current surge capacity. More detailed follow-up studies are needed to prepare a surge capacity protocol in the community., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)