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Background: Next-generation sequencing (NGS) has become widely available but molecular profiling-guided therapy (MGT) had not been well established in the real world due to lack of available therapies and expertise to match treatment. Our study was designed to test the feasibility of a nationwide platform of NGS-guided MGT recommended by a central molecular tumor board (cMTB) for metastatic solid tumors., Patients and Methods: Patients with advanced or metastatic solid tumors with available NGS results and without standard treatment were enrolled. The cMTB interpreted the patients' NGS reports and recommended the following: (i) investigational medicinal products (IMPs) approved in other indications; (ii) alternative treatments; (iii) clinical trials. The primary variables were the proportion of patients with actionable genomic alterations and those receiving MGT as per cMTB recommendations. Others included treatment duration (TD), overall response rate (ORR), disease control rate (DCR), and safety., Results: From February 2021 to February 2022, 193 cases [99 (51.3%) men; median age 58 years (range 24-88 years); median line of previous treatment 3 (range 0-9)] from 29 sites were enrolled for 60 cMTB sessions. The median time from case submission to cMTB discussion was 7 days (range 2-20 days), and to IMP treatment initiation was 28 days (range 14-90 days). Actionable genetic alterations were found in 145 patients (75.1%). A total of 89 (46.1%) patients received actual dosing of IMPs, and 10 (5.2%) were enrolled in cMTB-recommended clinical trials, achieving an MGT rate of 51.3%. ORR and DCR of IMPs were 10.1% and 72.5%, respectively. The median TD was 3.5 months [95% confidence interval (CI) 2.8-5.5 months], and the 4-month TD rate was 44.9%. The median overall survival of patients who received IMPs was 6.9 months (95% CI 5.2-10.0 months)., Conclusion: KOSMOS confirmed the feasibility of MGT recommended by the cMTB, achieving a high MGT match rate and promising effectiveness in heavily pretreated advanced cancer patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Monitoring health status at home has garnered increasing interest. Therefore, this study investigated the potential feasibility of using noncontact sensors in actual home settings. We searched PubMed for relevant studies published until February 19, 2024, using the keywords "home-based," "home," "monitoring," "sensor," and "noncontact." The studies included in this review involved the installation of noncontact sensors in actual home settings and the evaluation of their performance for health status monitoring. Among the 3 included studies, 2 monitored respiratory status during sleep and 1 monitored body weight and cardiopulmonary physiology. Measurements such as heart rate, respiratory rate, and body weight obtained with noncontact sensors were compared with the results obtained from polysomnography, polygraphy, and commercial scales. All included studies demonstrated that noncontact sensors produced results comparable to those of standard measurement tools, confirming their excellent capability for biometric measurements. Overall, noncontact sensors have sufficient potential for monitoring health status at home., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Molecular and transcription factor subtyping were recently introduced to identify patients with unique clinical features in small cell lung cancer (SCLC). However, its prognostic relevance is yet to be established. This study aims to investigate the clinical implications and prognostic significance of transcription factor subtyping in SCLC using immunohistochemistry., Methods: One hundred and ninety consecutive SCLC patients treated with platinum-based chemotherapy at a single institution were retrospectively reviewed. Expression of ASCL1, NeuroD1, POU2F3, and YAP1 was assessed by immunohistochemical staining and applied to determine the transcription factor subtype of each case., Results: The association among transcription factors was not entirely mutually exclusive. YAP1 expression was the most significant prognostic indicator compared with other transcription factors or their related subtypes. Among patients with limited-stage disease (LD), complete response (CR) rates were 46.2% and 22.4% in the YAP1-positive and YAP1-negative groups, respectively. The median duration of response among patients who achieved CR was 64.8 and 36.4 months in the YAP1-positive and YAP1-negative groups, respectively (P=0.06). Median overall survival (OS) in LD was 35.6 and 16.9 months in the YAP1-positive and YAP1-negative groups, respectively (P=0.03). In extensive-stage disease (ED), the median OS was 11.3 months for the YAP1-positive group and 11 months for the YAP1-negative group (P=0.03)., Conclusions: Positive expression of YAP1 can be associated with durable CR and favorable survival outcomes in patients with SCLC, especially in LD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-317/coif). The authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

This study focuses on enhancing the thermal properties and shape recovery performance of shape memory polymers (SMPs) through the application of carbon-based fillers. Single and mixed fillers were used to investigate their effects on the glass transition temperature (T g ), thermal conductivity, and shape recovery performance. The interaction among the three-dimensional (3D) structures of mixed fillers played a crucial role in enhancing the properties of the SMP. These interactions facilitated efficient heat transfer pathways and conserved strain energy. The application of mixed fillers resulted in substantial improvements, demonstrating a remarkable 290.37% increase in thermal conductivity for SMPCs containing 60 μm carbon fiber (CF) 10 wt% + graphite 20 wt% and a 60.99% reduction in shape recovery time for SMPCs containing CF 2.5 wt% + graphite 2.5 wt%. At a content of 15 wt%, a higher graphite content compared to CF improved the thermal conductivity by 37.42% and reduced the shape recovery time by 6.98%. The findings demonstrate that the application of mixed fillers, especially those with high graphite content, is effective in improving the thermal properties and shape recovery performance of SMPs. By using mixed fillers with high graphite content, the performance of the SMP showed significant improvement in situations where fast response times were required.

Background: Periprosthetic osteolysis is a prevalent complication following total ankle arthroplasty (TAA), implicating various cytokines in osteoclastogenesis as pivotal in this process. This study aimed to evaluate the relationship between osteolysis and the concentrations of osteoclastogenesis-related cytokines in synovial fluid and investigate its clinical value following TAA., Methods: Synovial fluid samples from 23 ankles that underwent revision surgery for osteolysis following TAA were analyzed as the osteolysis group. As a control group, we included synovial fluid samples obtained from 23 ankles during primary TAA for osteoarthritis. The receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in these samples was quantified using sandwich enzyme-linked immunosorbent assay techniques, and a bead-based multiplex immunoassay facilitated the detection of specific osteoclastogenesis-related cytokines., Results: RANKL levels averaged 487.9 pg/mL in 14 of 23 patients in the osteolysis group, with no detection in the control group's synovial fluid. Conversely, a significant reduction in OPG levels was observed in the osteolysis group ( p = 0.002), resulting in a markedly higher mean RANKL/OPG ratio (0.23) relative to controls ( p = 0.020). Moreover, the osteolysis group had increased concentrations of various osteoclastogenesis-related cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-8, IP-10, and monocyte chemotactic protein-1) in the synovial fluid relative to the control group., Conclusions: Our results demonstrated that periprosthetic osteolysis was associated with osteoclastogenesis activation through an elevated RANKL/OPG ratio following TAA. We assume that RANKL and other osteoclastogenesis-related cytokines in the synovial fluid have clinical value as a potential marker for the development and progression of osteolysis following TAA., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Researchers are increasingly interested in cell therapy using mesenchymal stem cells (MSCs) as an alternative remedy for osteoporosis, with fewer side effects. Thus, we isolated and characterized extracellular vesicles (EVs) from human adipose tissue-derived MSCs (hMSCs) and investigated their inhibitory effects on RANKL-induced osteoclast differentiation. Purified EVs were collected from the supernatant of hMSCs by tangential flow filtration. Characterization of EVs included typical evaluation of the size and concentration of EVs by nanoparticle tracking analysis and morphology analysis using transmission electron microscopy. hMSC-EVs inhibited RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by EV treatment of osteoclasts. In addition, EVs decreased RANKL-induced phosphorylation of p38 and JNK and expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. To elucidate which part of the hMSC-EVs plays a role in the inhibition of osteoclast differentiation, we analyzed miRNA profiles in hMSC-EVs. The results showed that has-miR122-5p was present at significantly high read counts. Overexpression of miR122-5p in BMDMs significantly inhibited RANKL-induced osteoclast differentiation and induced defects in F-actin ring formation and bone resorption. Our results also revealed that RANKL-induced phosphorylation of p38 and JNK and osteoclast-specific gene expression was decreased by miR122-5p transfection, which was consistent with the results of hMSC-EVs. These findings suggest that hMSC-EVs containing miR122-5p inhibit RANKL-induced osteoclast differentiation via the downregulation of molecular mechanisms and could be a preventive candidate for destructive bone diseases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: We evaluated changes in the smartphone use rate and time among Korean adolescents and their awareness of associated health problems., Methods: This study was a secondary analysis of the Korea Youth Risk Behavior Survey (2020-2023) conducted by the Korean Disease Control and Prevention Agency. The total number of enrolled adolescents aged 12-18 years was 214,526., Results: The weekly smartphone usage rate increased from 96.4% to 97.1% ( p = 0.03), with no significant changes observed in weekend usage. The average smartphone use time was 4.7 h on weekdays ( p = 0.17) and 6.6 h on weekends ( p = 0.37). Middle school adolescents had a higher weekday use rate than high school adolescents, but the average smartphone use time was significantly less. By 2023, the proportion of adolescents with overdependence was 28% ( n = 14,672). Additionally, 11.8% ( n = 6255) responded that they had experienced health problems due to smartphone use., Conclusions: The longer they used their smartphones for on the weekends, the more likely they considered their health to be worse. In conclusion, our youth population needs to be educated on the proper use of smartphones.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea., Patients and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response., Results: Thirteen (44.8%) of the 29 patients achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression., Conclusion: This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

The commercialization of 3D heterogeneous integration through hybrid bonding has accelerated, and accordingly, Cu-polymer bonding has gained significant attention as a means of overcoming the limitations of conventional Cu-SiO 2 hybrid bonding, offering high compatibility with other fabrication processes. Polymers offer robust bonding strength and a low dielectric constant, enabling high-speed signal transmission with high reliability, but suffer from low thermomechanical stability. Thermomechanical stability of polymers was not achieved previously because of thermal degradation and unstable anchoring. To overcome these limitations, wafer-scale Cu-polymer bonding via N-heterocyclic carbene (NHC) nanolayers was presented for 3D heterogeneous integration, affording ultrastable packing density, crystallinity, and thermal properties. NHC nanolayers were deposited on copper electrodes via electrochemical deposition, and wafer-scale 3D heterogeneous integration was achieved by adhesive bonding at 170 °C for 1 min. Ultrastable conductivity and thermomechanical properties were observed by the spatial mapping of conductivity, work function, and force-distance curves. With regard to the characterization of NHC nanolayers, low-temperature bonding, robust corrosion inhibition, enhanced electrical conductivity, back-end-of-line process compatibility, and fabrication process reduction, NHC Cu/polymer bonding provides versatile advances in 3D heterogeneous integration, indicating that NHC Cu/polymer bonding can be utilized as a platform for future 3D vertical chip architectures.

Vital signs are crucial for monitoring changes in patient health status. This review compared the performance of noncontact sensors with traditional methods for measuring vital signs and investigated the clinical feasibility of noncontact sensors for medical use. We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) database for articles published through September 30, 2023, and used the key search terms "vital sign," "monitoring," and "sensor" to identify relevant articles. We included studies that measured vital signs using traditional methods and noncontact sensors and excluded articles not written in English, case reports, reviews, and conference presentations. In total, 129 studies were identified, and eligible articles were selected based on their titles, abstracts, and full texts. Three articles were finally included in the review, and the types of noncontact sensors used in each selected study were an impulse radio ultrawideband radar, a microbend fiber-optic sensor, and a mat-type air pressure sensor. Participants included neonates in the neonatal intensive care unit, patients with sleep apnea, and patients with coronavirus disease. Their heart rate, respiratory rate, blood pressure, body temperature, and arterial oxygen saturation were measured. Studies have demonstrated that the performance of noncontact sensors is comparable to that of traditional methods of vital signs measurement. Noncontact sensors have the potential to alleviate concerns related to skin disorders associated with traditional skin-contact vital signs measurement methods, reduce the workload for healthcare providers, and enhance patient comfort. This article reviews the medical use of noncontact sensors for measuring vital signs and aimed to determine their potential clinical applicability.

Purpose: This study was conducted to develop a convolutional neural network (CNN) algorithm that can diagnose cervical foraminal stenosis using oblique radiographs and evaluate its accuracy., Materials and Methods: A total of 997 patients who underwent cervical MRI and cervical oblique radiographs within a 3-month interval were included. Oblique radiographs were labeled as "foraminal stenosis" or "no foraminal stenosis" according to whether foraminal stenosis was present in the C2-T1 levels based on MRI evaluation as ground truth. The CNN model involved data augmentation, image preprocessing, and transfer learning using DenseNet161. Visualization of the location of the CNN model was performed using gradient-weight class activation mapping (Grad-CAM)., Results: The area under the curve (AUC) of the receiver operating characteristic curve based on DenseNet161 was 0.889 (95% confidence interval, 0.851-0.927). The F1 score, accuracy, precision, and recall were 88.5%, 84.6%, 88.1%, and 88.5%, respectively. The accuracy of the proposed CNN model was significantly higher than that of two orthopedic surgeons (64.0%, p <0.001; 58.0%, p <0.001). Grad-CAM analysis demonstrated that the CNN model most frequently focused on the foramen location for the determination of foraminal stenosis, although disc space was also frequently taken into consideration., Conclusion: A CNN algorithm that can detect neural foraminal stenosis in cervical oblique radiographs was developed. The AUC, F1 score, and accuracy were 0.889, 88.5%, and 84.6%, respectively. With the current CNN model, cervical oblique radiography could be a more effective screening tool for neural foraminal stenosis., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Background: Systemic inflammation is believed to contribute to small cell lung cancer (SCLC) progression, but the underlying relationship remains unclear. Lipocalin-2, a potential biomarker of inflammation, has been implicated in various cancers but its prognostic value in SCLC is underexplored., Methods: We retrospectively analyzed 191 patients with SCLC (72 with limited-stage [LD] and 119 with extensive-stage) treated using platinum-based chemotherapy. Lipocalin-2 expression was evaluated using immunohistochemistry. Optimal cutoff values for lipocalin-2 and neutrophil-to-lymphocyte ratio (NLR) were determined using time-dependent receiver operating characteristic curve analysis. The pectoralis muscle index was used to assess sarcopenia., Results: In LD-SCLC, high lipocalin-2 expression was associated with worse progression-free survival (PFS; median: 7.0 vs. 15.9 months, p = 0.015) and overall survival (OS; median: 12.9 vs. 30.3 months, p = 0.035) compared with low lipocalin-2 expression. Patients were stratified into three prognostic groups by combining lipocalin-2 with NLR: low lipocalin-2/low NLR, high lipocalin-2/low NLR or low lipocalin-2/high NLR, and high lipocalin-2/high NLR (median PFS: 17.3 vs. 11.0 vs. 6.3 months, p = 0.004; median OS: 30.5 vs. 17.3 vs. 8.6 months, p = 0.002). Similar trends were observed when combining lipocalin-2 with the pectoralis muscle index. High lipocalin-2 expression was also associated with lower complete response rates (18.9% vs. 34.3%, p = 0.035). No significant prognostic implications were found for lipocalin-2 in extensive-stage SCLC., Conclusions: High lipocalin-2 expression is potentially associated with poorer survival in LD-SCLC. Combining lipocalin-2 with other inflammation-related markers could improve prognostic stratification., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

The continuous monitoring of the health status of patients is essential for the effective monitoring of disease progression and the management of symptoms. Recently, health monitoring using non-contact sensors has gained interest. Therefore, this study aimed to investigate the use of non-contact sensors for health monitoring in hospital settings and evaluate their potential clinical applications. A comprehensive literature search was conducted using PubMed to identify relevant studies published up to February 26, 2024. The search terms included "hospital," "monitoring," "sensor," and "non-contact." Studies that used non-contact sensors to monitor health status in hospital settings were included in this review. Of the 38 search results, five studies met the inclusion criteria. The non-contact sensors described in the studies were radar, infrared, and microwave sensors. These non-contact sensors were used to obtain vital signs, such as respiratory rate, heart rate, and body temperature, and were then compared with the results from conventional measurement methods (polysomnography, nursing records, and electrocardiography). In all the included studies, non-contact sensors demonstrated a performance similar to that of conventional health-related parameter measurement methods. Non-contact sensors are expected to be a promising solution for health monitoring in hospital settings., 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 Choo, Lee, Moon and Chang.)

Background: Avascular necrosis (AVN) is a medical condition characterized by the destruction of bone tissue due to a diminished blood supply. When the rate of tissue destruction surpasses the rate of regeneration, effective treatment becomes challenging, leading to escalating pain, arthritis, and bone fragility as the disease advances. A timely diagnosis is imperative to prevent and initiate proactive treatment for osteonecrosis. We explored the potential of differentially expressed proteins in serum-derived extracellular vesicles (EVs) as biomarkers for AVN of the femoral head in humans. We analyzed the genetic material contained in serum-derived exosomes from patients for early diagnosis, treatment, and prognosis of avascular necrosis., Methods: EVs were isolated from the serum of both patients with AVN and a control group of healthy individuals. Proteomic analyses were conducted to compare the expression patterns of these proteins by proteomic analysis using LC-MS/MS., Results: Our results show that the levels of IGHV3-23, FN1, VWF, FGB, PRG4, FCGBP, and ZSWIM9 were upregulated in the EVs of patients with AVN compared with those of healthy controls. ELISA results showed that VWF and PRG4 were significantly upregulated in the patients with AVN., Conclusions: These findings suggest that these EV proteins could serve as promising biomarkers for the early detection and diagnosis of AVN. Early diagnosis is paramount for effective treatment, and the identification of new osteonecrosis biomarkers is essential to facilitate swift diagnosis and proactive intervention. Our study provides novel insights into the identification of AVN-related biomarkers that can enhance clinical management and treatment outcomes., (© 2024. The Author(s).)

Background: Sagittal talar translation is an important factor influencing the sagittal alignment of total ankle arthroplasty (TAA). Thus, accurate measurement of sagittal talar translation is crucial. This study proposes a simple method (tibiotalar distance [TTD]) that can quantify talar translation without being affected by the ankle and subtalar joint condition or the talar component position in patients with TAA., Methods: We enrolled 280 eligible patients (296 ankles) who underwent primary TAA between 2005 and 2019 and retrospectively reviewed them for sagittal talar translation. The TTD was measured for each patient on weight-bearing lateral ankle radiographs by 3 raters. In addition, we analyzed interrater and intrarater reliability for the TTD method., Results: We found that the TTD method could quantify the talar translation and was not affected by the preoperative condition of the ankle joint surface, subtalar joint pathologies, or the postoperative talar component position. The TTD method showed an excellent intraclass correlation coefficient (> 0.9) in all interrater and intrarater reliability analyses. In the analysis of 157 healthy, unoperated contralateral ankles, we identified that TTD showed a Gaussian distribution ( p = 0.284) and a mean of 38.91 mm (normal range, 29.63-48.20 mm)., Conclusions: The TTD method is a simple and reliable method that could be applied to patients with TAA to assess the sagittal talar translation regardless of the pre-and postoperative joint condition and implantation status., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Background: Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform., Methods: The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment., Discussion: This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers., Trial Registration: NCT05525858., (© 2024. The Author(s).)

Cellular reprogramming technologies have been developed with different physicochemical factors to improve the reprogramming efficiencies of induced pluripotent stem cells (iPSCs). Ultrasound is a clinically applied noncontact biophysical factor known for regulating various cellular behaviors but remains uninvestigated for cellular reprogramming. Here, we present a new reprogramming strategy using low-intensity ultrasound (LIUS) to improve cellular reprogramming of iPSCs in vitro and in vivo. Under 3D microenvironment conditions, increased LIUS stimulation shows enhanced cellular reprogramming of the iPSCs. The cellular reprogramming process facilitated by LIUS is accompanied by increased mesenchymal to epithelial transition and histone modification. LIUS stimulation transiently modulates the cytoskeletal rearrangement, along with increased membrane fluidity and mobility to increase HA/CD44 interactions. Furthermore, LIUS stimulation with HA hydrogel can be utilized in application of both human cells and in vivo environment, for enhanced reprogrammed cells into iPSCs. Thus, LIUS stimulation with a combinatorial 3D microenvironment system can improve cellular reprogramming in vitro and in vivo environments, which can be applied in various biomedical fields., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

Aims: The purpose of this study was to assess the success rate and functional outcomes of bone grafting for periprosthetic bone cysts following total ankle arthroplasty (TAA). Additionally, we evaluated the rate of graft incorporation and identified associated predisposing factors using CT scan., Methods: We reviewed a total of 37 ankles (34 patients) that had undergone bone grafting for periprosthetic bone cysts. A CT scan was performed one year after bone grafting to check the status of graft incorporation. For accurate analysis of cyst volumes and their postoperative changes, 3D-reconstructed CT scan processed with 3D software was used. For functional outcomes, variables such as the Ankle Osteoarthritis Scale score and the visual analogue scale for pain were measured., Results: Out of 37 ankles, graft incorporation was successful in 30 cases. Among the remaining seven cases, four (10.8%) exhibited cyst re-progression, so secondary bone grafting was needed. After secondary bone grafting, no further progression has been noted, resulting in an overall 91.9% success rate (34 of 37) at a mean follow-up period of 47.5 months (24 to 120). The remaining three cases (8.1%) showed implant loosening, so tibiotalocalcaneal arthrodesis was performed. Functional outcomes were also improved after bone grafting in all variables at the latest follow-up (p < 0.05). The mean incorporation rate of the grafts according to the location of the cysts was 84.8% (55.2% to 96.1%) at the medial malleolus, 65.1% (27.6% to 97.1%) at the tibia, and 81.2% (42.8% to 98.7%) at the talus. Smoking was identified as a significant predisposing factor adversely affecting graft incorporation (p = 0.001)., Conclusion: Bone grafting for periprosthetic bone cysts following primary TAA is a reliable procedure with a satisfactory success rate and functional outcomes. Regular follow-up, including CT scan, is important for the detection of cyst re-progression to prevent implant loosening after bone grafting., Competing Interests: All authors report a grant from the National Research Foundation of Korea (NRF) funded by the Korea government Ministry of Science and ICT (MSIT) (Grant No. NRF-2017R1A2B4007245), related to this study., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

This paper addresses a joint training approach applied to a pipeline comprising speech enhancement (SE) and automatic speech recognition (ASR) models, where an acoustic tokenizer is included in the pipeline to leverage the linguistic information from the ASR model to the SE model. The acoustic tokenizer takes the outputs of the ASR encoder and provides a pseudo-label through K-means clustering. To transfer the linguistic information, represented by pseudo-labels, from the acoustic tokenizer to the SE model, a cluster-based pairwise contrastive (CBPC) loss function is proposed, which is a self-supervised contrastive loss function, and combined with an information noise contrastive estimation (infoNCE) loss function. This combined loss function prevents the SE model from overfitting to outlier samples and represents the pronunciation variability in samples with the same pseudo-label. The effectiveness of the proposed CBPC loss function is evaluated on a noisy LibriSpeech dataset by measuring both the speech quality scores and the word error rate (WER). The experimental results reveal that the proposed joint training approach using the described CBPC loss function achieves a lower WER than the conventional joint training approaches. In addition, it is demonstrated that the speech quality scores of the SE model trained using the proposed training approach are higher than those of the standalone-SE model and SE models trained using conventional joint training approaches. An ablation study is also conducted to investigate the effects of different combinations of loss functions on the speech quality scores and WER. Here, it is revealed that the proposed CBPC loss function combined with infoNCE contributes to a reduced WER and an increase in most of the speech quality scores.

Background: This study investigated the effects of systemic factors in response to intravitreal injections in patients with macular edema due to non-proliferative diabetic retinopathy (NPDR)., Methods: We retrospectively reviewed the medical records of patients treated with intravitreal injections for macular edema secondary to NPDR between January 2018 and January 2021. The patients were divided into three groups according to the injection response. When patients with diabetic macular edema showed 20µ or more reduction in central retinal thickness compared to baseline, they were classified as responsive group, and if not, they were classified as refractory group. The responsive group was further divided into the complete and incomplete response groups. Patients with complete disappearance of edema at seven months were classified as the complete response group, whereas those in which edema did not disappear were classified as the incomplete response group. The clinical characteristics of each group, including medical history, ophthalmic examination results, and laboratory examination results at the time of diagnosis, were analyzed., Results: Of the 112 eyes (91 patients) that satisfied the inclusion criteria, 89 (77 patients) in the responsive group and 23 (14 patients) in the refractory group were included in the analysis. The responsive group was further divided into the complete (51 eyes) and incomplete (38 eyes) response groups. The refractory group had significantly higher glycated hemoglobin levels and significantly lower estimated glomerular filtration rates than the responsive group (p = 0.026 and p = 0.012, respectively). In the multivariate logistic regression analysis, both factors were found to be significant in predicting the degree of response (all p < 0.05). No factor showed a significant difference between the incomplete and complete response groups(all p > 0.05)., Conclusions: In macular edema caused by NPDR, low glomerular filtration rates and high glycated hemoglobin levels may be used as predictors of poor response to intravitreal injection therapy. In addition to blood glucose control, education should be provided regarding the need for the continuous monitoring of renal function., (© 2024. The Author(s).)

Solute structure and its evolution in supersaturated aqueous solutions are key clues to understand Ostwald's step rule. Here, we measure the structural evolution of solute molecules in highly supersaturated solutions of KH 2 PO 4 (KDP) and NH 4 H 2 PO 4 (ADP) using a combination of electrostatic levitation and synchrotron X-ray scattering. The measurement reveals the existence of a solution-solution transition in KDP solution, caused by changing molecular symmetries and structural evolution of the solution with supersaturation. Moreover, we find that the molecular symmetry of H 2 PO 4 - impacts on phase selection. These findings manifest that molecular symmetry and its structural evolution can govern the crystallization pathways in aqueous solutions, explaining the microscopic origin of Ostwald's step rule., (© 2024. The Author(s).)

Purpose: In the treatment of non-small-cell lung cancer (NSCLC) with a driver mutation, the role of anti-PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase III study evaluates the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK -mutated NSCLC that progressed before TKI therapy., Materials and Methods: We compared the clinical efficacy of ABCP followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC) followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS)., Results: A total of 228 patients with activating EGFR mutation (n = 215) or ALK translocation (n = 13) were enrolled from 16 sites in the Republic of Korea and randomly assigned at 2:1 ratio to either ABCP (n = 154) or PC arm (n = 74). The median follow-up duration was 26.1 months (95% CI, 24.7 to 28.2). Objective response rates (69.5% v 41.9%, P < .001) and median PFS (8.48 v 5.62 months, hazard ratio [HR], 0.62 [95% CI, 0.45 to 0.86]; P = .004) were significantly better in the ABCP than PC arm. PFS benefit increased as PD-L1 expression increased, with an HR of 0.47, 0.41, and 0.24 for PD-L1 ≥1%, ≥10%, and ≥50%, respectively. Overall survival was similar between ABCP and PC arm (20.63 v 20.27 months, HR, 1.01 [95% CI, 0.69 to 1.46]; P = .975). The safety profile of the ABCP arm was comparable with that previously reported, with no additional safety signals, but higher rates of treatment-related adverse events were observed compared with the PC arm., Conclusion: To our knowledge, this study is the first randomized phase III study to demonstrate the clinical benefit of anti-PD-L1 antibody in combination with bevacizumab and chemotherapy in patients with EGFR- or ALK -mutated NSCLC who have progressed on relevant targeted therapy.

3D bioprinting has the potential for the rapid and precise engineering of hydrogel constructs that can mimic the structural and optical complexity of a healthy cornea. However, the use of existing light-activated bioinks for corneal printing is limited by their poor cytocompatibility, use of cytotoxic photoinitiators (PIs), low photo-crosslinking efficiency, and opaque/colored surface of the printed material. Herein, we report a fast-curable, non-cytotoxic, optically transparent bioprinting system using a new water-soluble benzoyl phosphinate-based PI and photocrosslinkable methacrylated hyaluronic acid (HAMA). Compared with commercially available PIs, the newly developed PI, lithium benzoyl (phenyl) phosphinate (BP), demonstrated increased photoinitiation efficiency under visible light and low cytotoxicity. Using a catalytic amount of BP, the HA-based bioinks quickly formed 3D hydrogel constructs under low-energy visible-light irradiation (405 nm, <1 J cm -2 ). The mechanical properties and printability of photocurable bioinks were further improved by blending low (10 kDa) and high (100 kDa) molecular weight (MW) HAMA by forming multilength networks. For potential applications as corneal scaffolds, stromal cell-laden dome-shaped constructs were fabricated using MW-blended HAMA/BP bioink and a digital light processing printer. The HA-based photocurable bioinks exhibited good cytocompatibility (80%-95%), fast curing kinetics (<5 s), and excellent optical transparency (>90% in the visible range), potentially making them suitable for corneal tissue engineering., (© 2024 IOP Publishing Ltd.)

The differentiation of naive CD8 + T cells into effector cells is important for establishing immunity. However, the effect of heterogeneous naive CD8 + T cell populations is not fully understood. Here, we demonstrate that steady-state naive CD8 + T cells are composed of functionally heterogeneous subpopulations that differ in their ability to differentiate into type 17 cytotoxic effector cells (Tc17) in a context of murine inflammatory disease models, such as inflammatory bowel disease and graft-versus-host disease. The differential ability of Tc17 differentiation is not related to T-cell receptor (TCR) diversity and antigen specificity but is inversely correlated with self-reactivity acquired during development. Mechanistically, this phenomenon is linked to differential levels of intrinsic TCR sensitivity and basal Suppressor of Mothers Against Decapentaplegic 3 (SMAD3) expression, generating a wide spectrum of Tc17 differentiation potential within naive CD8 + T cell populations. These findings suggest that developmental self-reactivity can determine the fate of naive CD8 + T cells to generate functionally distinct effector populations and achieve immense diversity and complexity in antigen-specific T-cell immune responses., (© 2024. The Author(s).)

Ambulatory blood pressure (ABP) and home blood pressure (HBP) monitoring is currently recommended for management of hypertension. Nonetheless, traditional HBP protocols could overlook diurnal fluctuations, which could also be linked with adverse cardiovascular outcomes. In this observational study, we studied among a group of treated hypertensive patients (N = 62, age: 52.4 ± 10.4 years) by using out-of-office ABP and wearable HBP. They received one session of 24-h ABP measurement with an oscillometric upper-arm monitor, and totally three sessions of 7-day/6-time-daily wearable HBP measurement separated in each month with HeartGuide. Controlled hypertension is defined as an average BP <130/80 mmHg for both daytime ABP and HBP. There was substantial reliability (intraclass correlation coefficient, ICC 0.883-0.911) and good reproducibility (Cohen's kappa = 0.600) for wearable HBP measurement, especially before breakfast and after dinner. Among all patients, 27.4% had both uncontrolled HBP and ABP, 30.6% had uncontrolled HBP only, while 6.5% had uncontrolled ABP only. Female gender and increased numbers of anti-hypertensive agents are correlated with controlled hypertension. Patients with uncontrolled hypertension had a significantly higher maximal daytime blood pressure, which was previously signified as an imperial marker for cardiovascular risk. In conclusion, wearable HBP monitoring in accordance with a dedicated daily-living schedule results in good reliability and reproducibility. Patients with an uncontrolled wearable HBP should benefit from repeated HBP or ABP measurement for risk stratification., (© 2024. The Author(s).)

Objective: This analysis of the first-line cohort of LASER201 study evaluated the efficacy and safety of lazertinib 240 mg as a frontline therapy for epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)., Methods: A total of 43 patients, with EGFR mutation-positive (Exon19Del, n = 24; L858R, n = 18; G719X, n = 1) locally advanced or metastatic NSCLC who had not previously received EGFR tyrosine kinase inhibitor (EGFR TKI) therapy, received once-daily lazertinib 240 mg. EGFR mutation status was confirmed by local or central testing. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review. Secondary efficacy endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), tumor shrinkage, and overall survival (OS)., Results: At the primary data cut-off (DCO; January 8, 2021), the ORR was 70 % (95 % confidence interval [CI]: 56.0-83.5), DCR was 86 % (95 % CI: 75.7-96.4) and the median DoR was 23.5 (95 % CI: 12.5-not reached) months. The median PFS was 24.6 (95 % CI: 12.2-30.2) months. At the final DCO (March 30, 2023), the median OS was not estimable and the median follow-up duration for OS was 55.2 [95 % CI: 22.8-55.7] months. OS rates at 36 months and 54 months were 66 % (95 % CI: 47.5-79.3 %) and 55 % (95 % CI: 36.6-70.7 %), respectively. The most commonly reported TEAEs were rash (54 %), diarrhea (47 %), pruritus (35 %), and paresthesia (35 %). No drug-related rash or pruritus TEAEs of grade 3 or higher were reported. Diarrhea and paresthesia of grade 3 or higher were reported in 3 (7 %) and 1 (2 %) patients, respectively., Conclusion: This analysis demonstrated long-term clinical benefit with lazertinib 240 mg in patients with EGFR-mutated NSCLC who had not previously received EGFR TKIs. The safety profile for lazertinib was tolerable and consistent with that previously reported., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Byoung Chul Cho has received research funding from MOGAM Institute, LG Chem, Oscotec Inc., Interpark Bio Convergence Corp, GI Innovation, GI Cell, Abion, Abbvie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Oncology, CJ Bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Eli Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, BridgeBio Therapeutics, Yuhan Corporation, ImmuneOncia, Illumina, Kanaph Therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center and Vertical Bio AG. He has received consulting fees from Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus Therapeutics, Ono Pharmaceutical, Onegene Biotechnology, Yuhan Corporation, Pfizer, Eli Lilly, GI Cell, Guardant Health, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint Medicines, RandBio, and Hanmi. He receives royalty from Champions Oncology, Crown Bioscience, Imagen and serves on the advisory board of Kanaph Therapeutics Inc., BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health, and Oscotech Inc, J INTS BIO, Therapex, Gilead, Amgen. He was an invited speaker for ASCO, AstraZeneca, Guardant Health, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, and Pfizer. He is on the board of directors for J INTS BIO. He is an employee of Yonsei University Health System and the founder of the DAAN Biotherapeutics. He owns stocks of TheraCanVac Inc., Gencurix Inc., BridgeBio Therapeutics, Kanaph Therapeutics Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp., and J INTS BIO. Ji-Youn Han reports research funding from Pfizer, Takeda, ONO, Roche; consulting fees from AstraZeneca, Janssen, Amgen, Oncobix, Merck, Novartis, Abion, Takeda, J INTS BIO and honoraria for lectures from AstraZeneca, Janssen, Takeda, Merck, Yuhan Corporation, Novartis and Pfizer and payment for expert testimony from AstraZeneca He participated in Data Safety Monitoring Board for AstraZeneca, Janssen, J INTS BIO. Ki Hyeong Lee reports grants from Merck Serono. He has received consulting fees from MSD, Pfizer, Eli Lilly, Yuhan Corporation, AstraZeneca, BMS. Yun-Gyoo Lee reports honoraria for lectures from AstraZeneca, MSD, Lilly, Boehringer Ingelheim and Yuhan. He participated in Data Safety Monitoring Board or Advisory Board for BeiGene, Dakeda, Guardant Health, Yuhan, Ono and Novartis. Dong-Wan Kim reports research funding to his institution from Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer Ingelheim, BMS, BridgeBio Therapeutics, Chong Keun Dang, Daiichi-Sankyo, GSK, Hanmi, InnoN, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery and Yuhan Corporation, and honoraria from the Korean Association for Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology, Taiwan Lung Cancer Society, Asian Thoracic Oncology Research Group. He reports travel support for attending meetings for the International Association for the Study of Lung Cancer, Asian Thoracic Oncology Research Group, Taiwan Lung Cancer Society. He provides medical writing assistance to Amgen, AstraZeneca, Boehringer-Ingelheim, BridgeBio Therapeutics, BMS, Chong Keun Dang, Daiichi-Sankyo, GSK, Pfizer, MSD, Merck, Merus, Novartis, Roche, Takeda, Yuhan Corporation. He participated in advisory boards for Amgen, AstraZeneca, BMS/Ono Pharmaceutical, Daiichi-Sankyo, GSK, Janssen, Meck, MSD, Pfizer, SK Biopharm, Takeda. He is on the Board of Directors for Asian Thoracic Oncology Research Group, Korean Association for Lung Cancer, Korean Cancer Association, and Korean Society of Medical Oncology. He is a scientific advisor for Health Insurance Review and Assessment Service, Republic of Korea. Eun Kyung Cho reports participation in data safety monitoring meeting for Yuhan Corporation for this clinical trial and received study drugs for conducting this clinical trial from Yuhan Corporation. Young Joo Min reports research funding from AstraZeneca, MSD, Merck, Ono Pharmaceutical, Yuhan Corporation, Amgen, Roche and honoraria from AstraZeneca, MSD, Merck, and Ono Pharmaceutical. Na Mi Lee, Jangyoung Wang, and Hyejoo Park are employees of Yuhan Corporation. Myung-Ju Ahn received consulting fees and research funding from AstraZeneca, Eli Lilly, MSD, Merck, Ono Pharmaceutical, Takeda, Yuhan Corporation, Amgen, Novartis, Roche, Alpha-Pharmaceuticals, and honoraria from AstraZeneca, Eli Lilly, MSD, Merck, Ono Pharmaceutical, Takeda, Yuhan Corporation, Amgen, Novartis and Roche. All other authors have no relevant relationships to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Xanthomonas oryzae pv. oryzae ( Xoo ) causes a devastating bacterial leaf blight in rice. Here, the antimicrobial effects of D-limonene, L-limonene, and its oxidative derivative carveol against Xoo were investigated. We revealed that carveol treatment at ≥ 0.1 mM in liquid culture resulted in significant decrease in Xoo growth rate (> 40%) in a concentration-dependent manner, and over 1 mM, no growth was observed. The treatment with D-limonene and L-limonene also inhibited the Xoo growth but to a lesser extent compared to carveol. These results were further elaborated with the assays of motility, biofilm formation and xanthomonadin production. The carveol treatment over 1 mM caused no motilities, basal level of biofilm formation (< 10%), and significantly reduced xanthomonadin production. The biofilm formation after the treatment with two limonene isomers was decreased in a concentration-dependent manner, but the degree of the effect was not comparable to carveol. In addition, there was negligible effect on the xanthomonadin production mediated by the treatment of two limonene isomers. Field emission-scanning electron microscope (FE-SEM) unveiled that all three compounds used in this study cause severe ultrastructural morphological changes in Xoo cells, showing shrinking, shriveling, and holes on their surface. Moreover, quantitative real-time PCR revealed that carveol and D-limonene treatment significantly down-regulated the expression levels of genes involved in virulence and biofilm formation of Xoo , but not with L-limonene. Together, we suggest that limonenes and carveol will be the candidates of interest in the development of biological pesticides.

Competing Interests: None

This experimental study was designed to evaluate the effect of ulinastatin, a urinary trypsin inhibitor, on postoperative cognitive dysfunction (POCD) in rats under general anesthesia with isoflurane, on the aspect of behavior, as evaluated using a Y-maze test and focusing on microglial activity. Ulinastatin (50,000 U/mL) and normal saline (1 mL) were randomly (1:1) administered intraperitoneally to the ulinastatin and control groups, respectively, before general anesthesia. Anesthesia with isoflurane 1.5 volume% was maintained for 2 h. The Y-maze test was used to evaluate cognitive function. Neuronal damage using caspase-1 expression, the degree of inflammation through cytokine detection, and microglial activation with differentiation of the phenotypic expression were evaluated. Twelve rats were enrolled in the study and evenly allocated into the two groups, with no dropouts from the study. The Y-maze test showed similar results in the two groups before general anesthesia (63 ± 12% in the control group vs. 64 ± 12% in the ulinastatin group, p = 0.81). However, a significant difference was observed between the two groups after general anesthesia (17 ± 24% in the control group vs. 60 ± 12% in the ulinastatin group, p = 0.006). The ulinastatin group showed significantly lower expression of caspase-1. Pro-inflammatory cytokine levels were significantly lower in the ulinastatin group than in the control group. The ulinastatin group had a significantly lower microglial activation (41.74 ± 10.56% in the control group vs. 4.77 ± 0.56% in the ulinastatin, p < 0.001), with a significantly lower activation of M1 phenotypes (52.19 ± 7.83% in the control group vs. 5.58 ± 0.76% in the ulinastatin group, p < 0.001). Administering ulinastatin before general anesthesia prevented neuronal damage and cognitive decline after general anesthesia, in terms of the aspect of behavior, as evaluated by the Y-maze test. The protective effect of ulinastatin was associated with the inhibition of microglial activation, especially the M1 phenotype.

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan., (© 2024. The Author(s).)

The primary objective of this study was to investigate the factors contributing to hyperglycemic adverse events (AEs) associated with the administration of remdesivir in hospitalized patients diagnosed with coronavirus disease 2019 (COVID-19). Furthermore, the study aimed to develop a risk score model employing various machine learning approaches. A total of 1262 patients were enrolled in this investigation. The relationship between covariates and hyperglycemic AEs was assessed through logistic regression analysis. Diverse machine learning algorithms were employed for the purpose of forecasting hyperglycemia-related complications. After adjusting for covariates, individuals with a body mass index ≥23 kg/m 2 , those using proton pump inhibitors, cholinergic medications, or individuals with cardiovascular diseases exhibited approximately 2.41-, 2.73-, 2.65-, and 1.97-fold higher risks of experiencing hyperglycemic AEs (95% CI 1.271-4.577, 1.223-6.081, 1.168-5.989, and 1.119-3.472, respectively). Multivariate logistic regression, elastic net, and random forest models displayed area under the receiver operating characteristic curve values of 0.65, 0.66, and 0.60, respectively (95% CI 0.572-0.719, 0.640-0.671, and 0.583-0.611, respectively). This study comprehensively explored factors associated with hyperglycemic complications arising from remdesivir administration and, concurrently, leveraged a range of machine learning methodologies to construct a risk scoring model, thereby facilitating the tailoring of individualized remdesivir treatment regimens for patients with COVID-19., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: Deep learning is an advanced machine-learning approach that is used in several medical fields. Here, we developed a deep learning model using an object detection algorithm to identify the L5 vertebra on anteroposterior lumbar spine radiographs, and assessed its detection accuracy., Methods: We retrospectively recruited 150 participants for whom both anteroposterior whole-spine and lumbar spine radiographs were available. The anteroposterior lumbar spine radiographs of these patients were used as the input data. Of the 150 images, 105 (70%) were randomly selected as the training set, and the remaining 45 (30%) were assigned to the validation set. YOLOv5x, of the YOLOv5 family model, was used to detect the L5 vertebra area., Results: The mean average precisions 0.5 and 0.75 of the trained L5 detection model were 99.2% and 96.9%, respectively. The model's precision was 95.7% and its recall was 97.8%. Furthermore, 93.3% of the validation data were correctly detected., Conclusion: Our deep learning model showed an outstanding ability to identify L5 vertebrae.

A noncontact sensor field is an innovative device that can detect, measure, or monitor physical properties or conditions without direct physical contact with the subject or object under examination. These sensors use a variety of methods, including electromagnetic, optical, and acoustic technique, to collect information about the target without physical interaction. Noncontact sensors find wide-ranging applications in various fields such as manufacturing, robotics, automobiles, security, environmental monitoring, space industry, agriculture, and entertainment. In particular, they are used in the medical field, where they provide continuous monitoring of patient conditions and offer opportunities in rehabilitation medicine. This article introduces the potential of noncontact sensors in the field of rehabilitation medicine.

Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC)., Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS)., Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment-related AEs occurred with lazertinib than gefitinib., Conclusion: Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Purpose: Limited research has been conducted on the prevalence of non-medical opioid use (NMOU) in Korean cancer patients who have received prescription opioids (PO). This study aimed to identify the potential proportion of NMOU in cancer patients who had been prescribed opioids in Korea., Methods: A retrospective cohort analysis was conducted on 14,728 patients who underwent cancer-related treatment between January 2009 and December 2019, using electronically collected data from a tertiary hospital in Korea. Information regarding the type and duration of opioid use was gathered. A detailed review of medical charts was carried out, focusing on patients who had been prescribed opioids for over 60 days beyond a 12-month period following the completion of their cancer treatment (long-term PO users)., Results: Out of the 5,587 patients who were prescribed PO and followed up for at least 12 months, 13 cases of NMOU were identified, representing 0.23% of the patient population. Among the 204 long-term PO users, the rate was 6.37% (13/204). The most commonly misused opioids were oxycodone and fentanyl. For the group confirmed to have NMOU, the median duration of prescription was 1,327 days in total. Of the 13 patients diagnosed with NMOU, 9 reported withdrawal symptoms, 3 exhibited craving behavior for opioids, and 1 experienced both symptoms., Conclusion: This study found that 0.23% of cancer patients who had been prescribed opioids in Korea demonstrated NMOU. Despite this relatively low rate, careful monitoring is necessary to minimize the risk of NMOU in this population, especially among long-term PO users., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2023 by Korean Society for Hospice and Palliative Care.)

To determine the relationship between ocular surface temperature (OST) and 0.1% cyclosporine A in patients with dry eye syndrome and meibomian gland dysfunction (MGD). This study retrospectively analyzed 35 eyes from 18 patients with dry eye disease (DED) and MGD, who were divided into two groups. Group 1 was treated with artificial tears, and eyelid margin scrubs without anti-inflammatory eye drops, while group 2 received the same treatment as group 1 along with 0.1% cyclosporine A. The ocular surface disease index (OSDI), tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), lipid layer thickness (LLT), meibum quality score (MQS), and OST were measured at baseline and 1 month later. Nineteen and 16 eyes were included in groups 1 and 2, respectively. Both groups showed a significant decrease in OSDI and OST; however, the decrease was more significant in group 2. No other significant differences in TMH, NIBUT, and LLT were observed; however, MQS significantly differed in group 2. This study found that 0.1% CsA administration can relieve symptoms in patients with DED and MGD although there were no definite keratitis clues, such as epithelial erosion. In addition, the conjunctival temperature showed a correlation with symptom improvement., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee 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.)

Background: Although the prognostic value of the Controlling Nutritional Status (CONUT) score in diffuse large B-cell lymphoma (DLBCL) has been reported in several previous studies, its clinical relevance for the presence of sarcopenia has not been assessed., Methods: In this study, 305 DLBCL patients were reviewed. They were categorized into normal/mild (n = 219) and moderate/severe (n = 86) CONUT groups. Sarcopenia was assessed using the L3-skeletal muscle index measured by baseline computed tomography imaging. Based on CONUT score and sarcopenia, patients were grouped: A (normal/mild CONUT and no sarcopenia), B (either moderate/severe CONUT or sarcopenia, but not both), and C (both moderate/severe CONUT and sarcopenia)., Results: The moderate/severe CONUT group showed higher rates of ≥ grade 3 febrile neutropenia, thrombocytopenia, non-hematologic toxicities, and early treatment discontinuation not related to disease progression, compared to the normal/mild CONUT group. The moderate/severe CONUT group had a lower complete response rate (58.1% vs. 80.8%) and shorter median overall survival (18.5 vs. 162.6 months) than the normal/mild group. Group C had the poorest prognosis with a median survival of 8.6 months, while groups A and B showed better outcomes (not reached and 60.1 months, respectively). Combining CONUT score and sarcopenia improved the predictive accuracy of the Cox regression model (C-index: 0.763), compared to the performance of using either CONUT score (C-index: 0.754) or sarcopenia alone (C-index: 0.755)., Conclusions: In conclusion, the moderate/severe CONUT group exhibited treatment intolerance, lower response, and poor prognosis. Additionally, combining CONUT score and sarcopenia enhanced predictive accuracy for survival outcomes compared to individual variables., (© 2023. The Author(s).)

The dynamic diamond anvil cell (dDAC) technique has attracted great interest because it possibly provides a bridge between static and dynamic compression studies with fast, repeatable, and controllable compression rates. The dDAC can be a particularly useful tool to study the pathways and kinetics of phase transitions under dynamic pressurization if simultaneous measurements of physical quantities are possible as a function of time. We here report the development of a real-time event monitoring (RTEM) system with dDAC, which can simultaneously record the volume, pressure, optical image, and structure of materials during dynamic compression runs. In particular, the volume measurement using both Fabry-Pérot interferogram and optical images facilitates the construction of an equation of state (EoS) using the dDAC in a home-laboratory. We also developed an in-line ruby pressure measurement (IRPM) system to be deployed at a synchrotron x-ray facility. This system provides simultaneous measurements of pressure and x-ray diffraction in low and narrow pressure ranges. The EoSs of ice VI obtained from the RTEM and the x-ray diffraction data with the IRPM are consistent with each other. The complementarity of both RTEM and IRPM systems will provide a great opportunity to scrutinize the detailed kinetic pathways of phase transitions using dDAC., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Endometriosis, which is the presence of endometrial stroma and glands outside the uterus, is one of the most frequently diagnosed gynecologic diseases in reproductive women. Patients with endometriosis suffer from various pain symptoms such as dysmenorrhea, dyspareunia, and chronic pelvic pain. The pathophysiology for chronic pain in patients with endometriosis has not been fully understood. Altered inflammatory responses have been shown to contribute to pain symptoms. Increased secretion of cytokines, angiogenic factors, and nerve growth factors has been suggested to increase pain. Also, altered distribution of nerve fibers may also contribute to chronic pain. Aside from local contributing factors, sensitization of the nervous system is also important in understanding persistent pain in endometriosis. Peripheral sensitization as well as central sensitization have been identified in patients with endometriosis. These sensitizations of the nervous system can also explain increased incidence of comorbidities related to pain such as irritable bowel disease, bladder pain syndrome, and vulvodynia in patients with endometriosis. In conclusion, there are various possible mechanisms behind pain in patients with endometriosis, and understanding these mechanisms can help clinicians understand the nature of the pain symptoms and decide on treatments for endometriosis-related pain symptoms.

A 6 year-old spayed female Poodle presented with a mandibular mass. Radiographic examination revealed osteolysis from the right mandibular canine to the fourth premolar, along with horizontal bone loss and dorsal displacement of the right mandibular first and second premolars. Skull cone beam computed tomography revealed osteolysis at the level of the right mandibular canine and fourth premolar. A destructive bone lesion was observed in the apical area of the right mandibular canine, with mass invasion of the interradicular bone of the right mandibular first molar near the mandibular canal. Consequently, unilateral total mandibulectomy and skin flap surgery were performed. Histopathological examination revealed poorly demarcated and infiltrative neoplastic epithelial cells that formed small islands and trabeculae. Neoplastic cells exhibited the malignant features of cytological atypia and high mitotic activity. Furthermore, the neoplastic epithelial cells frequently showed ghost cell changes and were diagnosed as ghost cell odontogenic carcinoma (GCOC). The dog was followed up for 1 year, during which no severe complications or local recurrence was observed, except for slight mandibular drift, tongue protrusion, and drooling. This case report describes the clinical features, diagnostic imaging, and histologic features of an unreported GCOC in a dog and the favorable outcome following surgical resection., 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 © 2023 Kim, Lee, Kim, Han, Han and Park.)

Improvements in long read DNA sequencing and related techniques facilitated the generation of complex eukaryotic genomes. Despite these advances, the quality of constructed plant reference genomes remains relatively poor due to the large size of genomes, high content of repetitive sequences, and wide variety of ploidy. Here, we developed the de novo sequencing and assembly of high polyploid plant genome, Hibiscus syriacus, a flowering plant species of the Malvaceae family, using the Oxford Nanopore Technologies and Pacific Biosciences Sequel sequencing platforms. We investigated an efficient combination of high-quality and high-molecular-weight DNA isolation procedure and suitable assembler to achieve optimal results using long read sequencing data. We found that abundant ultra-long reads allow for large and complex polyploid plant genome assemblies with great recovery of repetitive sequences and error correction even at relatively low depth Nanopore sequencing data and polishing compared to previous studies. Collectively, our combination provides cost effective methods to improve genome continuity and quality compared to the previously reported reference genome by accessing highly repetitive regions. The application of this combination may enable genetic research and breeding of polyploid crops, thus leading to improvements in crop production., (© 2023. Springer Nature Limited.)

Background: Cage subsidence after oblique lumbar interbody fusion (OLIF) induces restenosis and adversely affects patient outcomes. Many studies have investigated the causes of subsidence, one of which is endplate fracture (EF). This study aimed to identify predictors of EF after OLIF., Methods: This retrospective study reviewed consecutive patients who underwent OLIF at a single institute between August 2019 and February 2022. A total of 104 patients were enrolled. The patients' demographic data and surgical details were collected through chart reviews. Radiographic variables were measured. Related variables were also analyzed using binomial logistic regression, dividing each group into those with versus without EF., Results: EF occurred at 30 of 164 levels (18.3%), and the binary logistic analysis revealed that sex (odds ratio [OR], 11.07), inferior endplate concave depth (OR, 1.95), disc wedge angle (OR, 1.22), lumbar lordosis (OR, 1.09), pelvic incidence (OR, 1.07), sagittal vertical axis (OR, 1.02), sacral slope (OR, 0.9), L3-4 level (OR, 0.005), and L4-5 level (OR, 0.004) were significantly related to EF., Conclusions: OLIF in older Asian patients should be performed carefully after recognizing the high possibility of EF and confirming the factors that should be considered preoperatively., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2023 by The Korean Orthopaedic Association.)

Introduction: Lazertinib is a third-generation central nervous system-penetrant tyrosine kinase inhibitor targeting mutant EGFR in NSCLC. Lazertinib exhibited improved efficacy versus gefitinib in the LASER301 study; this subset analysis compared lazertinib with gefitinib among Asian patients., Methods: The phase 3 LASER301 study evaluated lazertinib efficacy and safety in treatment-naive patients with EGFR-mutated (exon 19 deletion or L858R) locally advanced or metastatic NSCLC. Patients were randomized one-to-one and received either lazertinib or gefitinib. The primary end point was investigator-assessed progression-free survival using Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included overall survival, objective response rate, duration of response, and safety., Results: Between February 13, 2020, and July 29, 2022, among 258 patients of Asian descent, the median progression-free survival was significantly longer with lazertinib than gefitinib (20.6 versus 9.7 mo; hazard ratio: 0.46; 95% confidence interval [CI]: 0.34-0.63, p < 0.001), and the benefit was consistent across predefined subgroups (exon 19 deletion, L858R, baseline central nervous system metastases). Objective response rate and disease control rates were similar between treatment groups. The median duration of response was 19.4 months (95% CI: 16.6-24.9) versus 9.6 months (95% CI: 6.9-12.4) in the lazertinib versus gefitinib group. Adverse event rates in Asian patients were comparable with the overall LASER301 population. Adverse events leading to discontinuation in the lazertinib and gefitinib groups were 13% and 12%, respectively., Conclusions: In LASER301, efficacy and safety results in Asian patients were consistent with the overall population. Lazertinib exhibited better efficacy than gefitinib in Asian patients with a tolerable safety profile., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background/aims: Little attention is paid to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Korea due to the rarity of the disease. With its rising incidence, we aimed to evaluate recent changes in treatment patterns and survival outcomes of patients with CLL/SLL., Methods: A total of 141 patients diagnosed with CLL/SLL between January 2010 and March 2020 who received systemic therapy were analyzed in this multicenter retrospective study., Results: The median patient age was 66 years at diagnosis, and 68.1% were male. The median interval from diagnosis to initial treatment was 0.9 months (range: 0-77.6 months), and the most common treatment indication was progressive marrow failure (50.4%). Regarding first-line therapy, 46.8% received fludarabine, cyclophosphamide, plus rituximab (FCR), followed by chlorambucil (19.9%), and obinutuzumab plus chlorambucil (GC) (12.1%). The median progression-free survival (PFS) was 49.3 months (95% confidence interval [CI], 32.7-61.4), and median overall survival was not reached (95% CI, 98.4 mo- not reached). Multivariable analysis revealed younger age (≤ 65 yr) (hazard ratio [HR], 0.46; p < 0.001) and first-line therapy with FCR (HR, 0.64; p = 0.019) were independently associated with improved PFS. TP53 aberrations were observed in 7.0% (4/57) of evaluable patients. Following reimbursement, GC became the most common therapy among patients over 65 years and second in the overall population after 2017., Conclusion: Age and reimbursement mainly influenced treatment strategies. Greater effort to apply risk stratifications into practice and clinical trials for novel agents could help improve treatment outcomes in Korean patients.

Application of Si anodes is hindered by severe capacity fading due to pulverization of Si particles during the large volume changes of Si during charge/discharge and repeated formation of the solid-electrolyte interphase. To address these issues, considerable efforts have been devoted to the development of Si composites with conductive carbons (Si/C composites). However, Si/C composites with high C content inevitably show low volumetric capacity because of low electrode density. For practical applications, the volumetric capacity of a Si/C composite electrode is more important than gravimetric capacity, but volumetric capacity in pressed electrodes is rarely reported. Herein, a novel synthesis strategy is demonstrate for a compact Si nanoparticle/graphene microspherical assembly with interfacial stability and mechanical strength achieved by consecutively formed chemical bonds using 3-aminopropyltriethoxysilane and sucrose. The unpressed electrode (density: 0.71 g cm -3 ) shows a reversible specific capacity of 1470 mAh g -1 with a high initial coulombic efficiency of 83.7% at a current density of 1 C-rate. The corresponding pressed electrode (density: 1.32 g cm -3 ) exhibits high reversible volumetric capacity of 1405 mAh cm -3 and gravimetric capacity of 1520 mAh g -1 with a high initial coulombic efficiency of 80.4% and excellent cycling stability of 83% over 100 cycles at 1 C-rate., (© 2023 Wiley-VCH GmbH.)