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Min-Kyung Ji,1,&ast; Yaerim Chun,2,&ast; Geonwoo Jeong,3 Hyun-Seung Kim,4 Won-Jae Kim,5 Je-Hwang Ryu,6 Hoonsung Cho,3 Hyun-Pil Lim1,2 1Dental 4D Research Center, Chonnam National University, Gwangju, Republic of Korea; 2Department of Prosthodontics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea; 3Department of Materials Science and Engineering, Chonnam National University, Gwangju, Republic of Korea; 4KJ Meditech Co., Ltd, Gwangju, Republic of Korea; 5Department of Oral Physiology, School of Dentistry, Stem Cell Secretome Research Center, Chonnam National University, Gwangju, Republic of Korea; 6Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Hyun-Pil Lim, Department of Prosthodontics, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea, Tel +82-10-2645-7528, Fax +82-62-530-5577, Email mcnihil@jnu.ac.kr Hoonsung Cho, Department of Materials Science and Engineering, Chonnam National University, Gwangju, 61186, Republic of Korea, Tel/Fax +82-62-530-1717, Email cho.hoonsung@jnu.ac.krPurpose: This study aimed to confirm the synergy effect of these two materials by evaluating osteoblast and antibacterial activity by applying a double-layered hydroxyapatite(HA) zirconium oxide(ZrO2) coating to titanium.Methods: The specimens used in this study were divided into four groups: a control group (polished titanium; group T) and three experimental groups: Group TH (RF magnetron sputtered HA deposited titanium), Group Z (ZrO2 ALD deposited titanium), and Group ZH (RF magnetron sputtered HA and ZrO2 ALD deposited titanium). The adhesion of Streptococcus mutans (S.mutans) to the surface was assessed using a crystal violet assay. The adhesion, proliferation, and differentiation of MC3T3-E1 cells, a mouse osteoblastic cell line, were assessed through a WST-8 assay and ALP assay.Results: Group Z showed a decrease in the adhesion of S. mutans (p < 0.05) and an improvement in osteoblastic viability (p < 0.0083). Group TH and ZH showed a decrease in adhesion of S. mutans (p < 0.05) and an increase in osteoblastic cell proliferation and cell differentiation (p < 0.0083). Group ZH exhibited the highest antibacterial and osteoblastic differentiation.Conclusion: In conclusion double-layered HA and ZrO2 deposited on titanium were shown to be more effective in inhibiting the adhesion of S. mutans, which induced biofilm formation, and increasing osteoblastic differentiation involved in osseointegration by the synergistic effect of the two materials.Keywords: zirconium oxide, hydroxyapatite, atomic layer deposition, radio frequency magnetron sputter, osteoblast activity, antibacterial effect

Hong-Joo Kim,1 Seon-Ki Lee,2 Hyun-Seung Kim,3 Won-Jae Kim,4 Je-Hwang Ryu,5 Min-Kyung Ji,6 Hyun-Pil Lim1 1Department of Prosthodontics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea; 2Department of Prosthodontics, Daejeon Dental Hospital, Wonkwang University, Daejeon, Republic of Korea; 3KJ Meditech Co., Ltd, Gwangju, Republic of Korea; 4Department of Oral Physiology, School of Dentistry, Stem cell Secretome Research Center, Chonnam National University, Gwangju, Republic of Korea; 5Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea; 6Dental 4D Research Center, Chonnam National University, Gwangju, Republic of KoreaCorrespondence: Hyun-Pil Lim, Department of Prosthodontics, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea, Tel +82-10-2645-7528, Fax +82-62-530-5639, Email mcnihil@jnu.ac.kr Min-Kyung Ji, Dental 4D Research Center, Chonnam National University, Gwangju, 61186, Republic of Korea, Tel +82-10-8432-3639, Fax +82-62-530-5639, Email perizimin@gmail.comPurpose: Atomic layer deposition (ALD) is a method that can deposit zirconia uniformly on an atomic basis. The effect of deposited zirconia on titanium implants using ALD was evaluated in vivo.Methods: Machined titanium implants (MTIs) were used as the Control. MTIs treated by sandblasting with large grit and acid etching (SA) and MTIs deposited with zirconia using ALD are referred to as Groups S and Z, respectively. Twelve implants were prepared for each group. Six rabbits were used as experimental animals. To evaluate the osteogenesis and osteocyte aspects around the implants, radiological and histological analyses were performed. The bone-to-implant contact (BIC) ratio was measured and statistically analyzed to evaluate the osseointegration capabilities.Results: In the micro-CT analysis, more radiopaque bone tissues were observed around the implants in Groups S and Z. Histological observation found that Groups S and Z had more and denser mature bone tissues around the implants in the cortical bone area. Many new and mature bone tissues were also observed in the medullary cavity area. For the BIC ratio, Groups S and Z were significantly higher than the Control in the cortical bone area (P < 0.017), but there was no significant difference between Groups S and Z.Conclusion: MTIs deposited with zirconia using ALD (Group Z) radiologically and histologically showed more mature bone formation and activated osteocytes compared with MTIs (Control). Group Z also had a significantly higher BIC ratio than the Control. Within the limitations of this study, depositing zirconia on the surface of MTIs using ALD can improve osseointegration in vivo.Keywords: atomic layer deposition, ALD, zirconia, machined titanium implant, bone-to-implant contact ratio, BIC, osseointegration

Eun Chong Yoon,1 So-My Koo,1 Hye Yun Park,2 Ho Cheol Kim,3 Woo Jin Kim,4 Ki Uk Kim,5 Ki-Suck Jung,6 Kwang Ha Yoo,7 Hyoung Kyu Yoon,8 Hee-Young Yoon1 1Division of Allergy and Respiratory Diseases, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea; 2Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 3Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Republic of Korea; 4Department of Internal Medicine and Environmental Health Center, Kangwon National University, Chuncheon, Republic of Korea; 5Department of Internal Medicine, Pusan National University Hospital, Busan, Republic of Korea; 6Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea; 7Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 8Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaCorrespondence: Hee-Young Yoon, Soonchunhyang University Seoul Hospital, 59, Daesagwan-ro, Yongsan-gu, Seoul, 04401, Republic of Korea, Tel +82-10-8728-6950, Fax +82-2-709-9554, Email yhyoung85@schmc.ac.krPurpose: Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic inflammation. Acute exacerbation of COPD (AECOPD) manifests as acute worsening of respiratory symptoms and is associated with high morbidity and mortality. The aim of the present study was to evaluate the predictive value of white blood count (WBC) and its derived inflammatory biomarkers for AECOPD.Methods: From the Korean COPD Subgroup Study cohort, a prospective and multicenter observational study, 826 patients who had baseline complete blood count (CBC) and 3-year AECOPD data were included. Follow-up CBC data at 1 (n = 385), 2 (n = 294), and 3 (n = 231) years were collected for available patients. The primary outcome was the occurrence of AECOPD at 3 years. The risk of AECOPD was evaluated using a binary logistic analysis.Results: The cumulative incidences of 12-, 24-, and 36-month AECOPD were 47.6%, 60.5%, and 67.6%, respectively. Patients with AECOPD at 3 years had higher baseline WBC counts, neutrophil counts, neutrophil/lymphocyte ratio (NLR), and neutrophil/monocyte ratio than those without AECOPD. Higher WBC count, neutrophil count, and NLR were associated with the 3-year occurrence of AECOPD in the univariate analysis, but only the higher neutrophil count was a significant risk factor (odds ratio [OR] = 1.468; 95% confidence interval [CI]: 1.024– 2.104) in the covariates-adjusted analysis. In the analysis of changes in inflammatory parameters, a decrease in the platelet count (OR = 0.502; 95% CI: 0.280– 0.902) and NLR (OR = 0.535; 95% CI: 0.294– 0.974) at 2 years and an increase in the eosinophil count (OR = 2.130; 95% CI: 1.027– 4.416) at 3 years were significantly associated with AECOPD in the adjusted analysis.Conclusion: Our data suggest that a high baseline WBC count, particularly neutrophil count, was associated with a higher incidence of long-term AECOPD.Keywords: blood cell count, blood platelets, eosinophils, lymphocytes, neutrophils, pulmonary disease, chronic obstructive

The incidence of anaplastic large cell lymphoma is 0.25 cases per 100,000 people. It usually causes lymphadenopathy and B symptoms; however, diverse cutaneous manifestations can also be observed. We report a rare case of anaplastic large cell lymphoma of the scalp, which presented similarly to a ruptured epidermal cyst. A 77-year-old woman visited the outpatient clinic complaining of scalp masses that had appeared 2 months before. One week before her visit, she had undergone incision and drainage at a local clinic but showed no improvement. Before surgery, facial magnetic resonance imaging revealed two suspicious ruptured cystic masses. Surgical excision was performed with a 1-cm free margin from the soft mass. Histopathology confirmed anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. After wide excision and skin grafting for wound reconstruction, followed by consultation with a hemato-oncologist and radiation oncologist, chemotherapy was planned to prevent recurrence. Differentiating anaplastic lymphoma kinase-negative anaplastic large cell lymphoma of the scalp from a ruptured epidermal cyst-like mass proved challenging. We recommend considering the possibility of anaplastic large cell lymphoma if an epidermal cyst-like mass does not respond to antibiotics or conventional dressing, as illustrated by our rare case.

Background: In understanding the pathophysiology of pulmonary fibrosis (PF), macrophage plasticity has been implicated with a crucial role in the fibrogenic process. Growing evidence indicates that accumulation of M2 macrophages correlates with the progression of PF, suggesting that targeted modulation of molecules that influence M2 macrophage polarization could be a promising therapeutic approach for PF. Here, we demonstrated a decisive role of C-X-C motif chemokine ligand 11 (CXCL11) in driving M1 macrophage polarization to alleviate PF in the bleomycin-induced murine model., Results: We intravenously administered secretome derived from naïve (M0) and polarized macrophages (M1 and M2) into PF mice and found that lung fibrosis was effectively reversed in only the M1-treated group, with modulation of the M1/M2 ratio toward the ratio of the control group. These findings suggest that the factors secreted from M1 macrophages contribute to alleviating PF by targeting macrophages and reshaping the immunofibrotic environment in a paracrine manner. Secretome analysis of macrophages identified CXCL11 as an M1-specific chemokine, and administration of recombinant CXCL11 effectively improved fibrosis with the reduction of M2 macrophages in vivo. Furthermore, a mechanistic in vitro study revealed that CXCL11 reprogrammed macrophages from M2 to M1 through the activation of pERK, pAKT, and p65 signaling., Conclusions: Collectively, we demonstrate an unprecedented role for M1 macrophage-derived CXCL11 as an inducer of M1 macrophage polarization to revert the fibrogenic process in mice with PF, which may provide a clinically meaningful benefit., Competing Interests: Declarations Ethics approval and consent to participate The experiment was approved by the Institutional Animal Care and Use Committee (IACUC), Kangwon National University (IACUC No. KW-220509-1). Consent for publication Not applicable. Competing interests The authors have declared that no competing interest exists., (© 2024. The Author(s).)

Background: The choice of the deep inferior epigastric perforator (DIEP) flap for breast reconstruction has increased. Three-dimensional (3D) models of DIEP flaps have been introduced with advances in 3D technology to assist the tedious intramuscular dissection of the pedicle. This study presents the process of creating an ideal 3D model for a DIEP flap., Methods: Collaboration among various professionals, including surgeons, radiologists, and 3D-printing model makers, is essential for manufacturing suitable 3D-printing DIEP models. Our team facilitated the collaboration process by sharing the virtual 3D model via a uniform resource locator (URL) using an online platform accessible on mobile devices., Results: During collaboration in 3D DIEP model-making, we continuously upgraded the model to a better version. The model was modified according to the surgeon's preference from a 1:1 ratio size to a handheld size. Additionally, we achieved significant advancements over conventional methods, including improved visualization of detailed vessel pathways with separation of arteries and veins, tissue transparency, and superficial inferior epigastric vein (SIEV)., Conclusions: Through 3D model-making collaborations, our team successfully developed a 3D DIEP model with translucency and visualized arteries and veins separately with accentuation of the perforators, including SIEV tracing, which is more accurate. This ideal 3D model for the DIEP flap enables the selection of a perforator vessel that is safe and easy to dissect to lower complications and procedure time and will be of great help to less experienced surgeons., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The aberrant activation of fibroblast growth factor (FGF) and FGF receptor (FGFR)-mediated signaling pathways are associated with cancer development, including hepatocellular carcinoma (HCC). A novel series of imidazo[1',2':1,6]pyrido[2,3-d]pyrimidine, containing an acrylamide covalent warhead, were synthesized as selective FGFR 1-4 inhibitors. Compound 7n was identified as the most potent inhibitor against FGFR1, 2, and 4, with IC 50 values of 8/4 nM (FGFR1/2) and 3.8 nM (FGFR4), and the covalent docking analyses suggested that 7n form a covalent adduct with cysteine residue on the hinge or p-loop of FGFR. Compound 7n exhibited a favorable pharmacokinetic profile and significant in vivo antitumor efficacy in human liver cancer xenograft mouse models (xenograft, FGF/FGFR-dependent HCC cells)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The clearwing moth, Synanthedon bicingulata Staudinger, 1887 (Lepidoptera: Sesiidae), is a serious pest that infests cherry trees. This species, which is distributed in South Korea, was once regarded as S. hector found in Japan, but renamed as S. bicingulata based on morphology. Molecular data for this species are not available. Hence, we sequenced the 16,255-bp long complete mitochondrial genome (mitogenome) of S. bicingulata . Phylogenetic analyses in the Cossoidea superfamily supported monophyly of the Synanthedon genus and Synanthedonini tribe. This newly sequenced mitogenome of S. bicingulata will be useful for studies in a diverse field of evolutionary study., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

This review presents current knowledge on applying bioelectrochemical sensors to monitor soil fertility through microbial activity and discusses future perspectives. Soil microbial activity is considered an indicator of soil fertility due to the interconnected relationship between soil nutrient composition, microbiome, and plant productivity. Similarities between soils and bioelectrochemical reactors provide the foundation for the design of bioelectrochemical sensors driven by microorganisms enriched as electrochemically active biofilms on polarized electrodes. The biofilm can exchange electrons with electrodes and metabolites with the nearby microbiome to generate electrochemical signals that inform of microbiome functions and nutrient bioavailability. Such mechanisms can be harnessed as a bioelectrochemical sensor for proxy monitoring of soil fertility to address the need for real-time monitoring of soils., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Male-male social interactions exert a substantial impact on the transcriptional regulation of genes associated with aggression and mating behavior in male Drosophila melanogaster. Throughout our comprehensive genetic screening of aggression-related genes, we identified that the majority of mutants for these genes are associated with rival-induced and visually-oriented mating behavior, longer-mating-duration (LMD). The majority of mutants with upregulated genes in single-housed males significantly altered LMD behavior but not copulation latency, suggesting a primary regulation of mating duration. Single-cell RNA sequencing revealed that LMD-related genes are predominantly co-expressed with male-specific genes like dsx and Cyp6a20 in specific cell populations, especially in cone cells. Functional validation confirmed the roles of these genes in mediating LMD. Expression of LMD genes like Cyp6a20, Cyp4d21, and CrzR was enriched in cone cells, with disruptions in cone cell-specific expression of CrzR and Cyp4d21 leading to disrupted LMD. We also identified a novel gene, CG10026/Macewindu, that reversed LMD when overexpressed in cone cells. These findings underscore the critical role of cone cells as a pivotal site for the expression of genes involved in the regulation of LMD behavior. This study provides valuable insights into the intricate mechanisms underlying complex sexual behaviors in Drosophila., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Objectives: Atrial fibrillation (AF) is one of the notorious risk factors in acute ischemic stroke (AIS), and the use of anticoagulants has been shown to be effective in preventing ischemic stroke in AF patients. Therefore, identifying AF in AIS patients has become increasingly important. However, the impact of brain imaging and cardiac indices on the development of new AF after stroke remains unclear., Methods: A consecutive series of AIS patients who were admitted to the Ulsan University Hospital between January 2013 and December 2019 were identified. Patients with relevant ischemic brain lesions on MRI were included, and those without echocardiography data were excluded. We included and classified the AF patients who had the disease prior to or during hospitalization or met the criteria for cryptogenic stroke (CS). Differences in baseline characteristics, stroke risk factors, stroke severity, insular lesion, and echocardiographic data were investigated among each group., Results: A total of 850 patients were enrolled in the study, comprising 231 patients with AF detected after stroke (AFDAS), 287 patients with known AF (KAF), and 350 patients with CS. Compared with KAF, patients with AFDAS had a lower prevalence of underlying coronary heart disease and stroke history. They had greater right insular cortex lesions and lesser left atrial enlargement in unadjusted analysis. Following adjusted analysis, the involvement of the right insular cortex was found to be associated with the AFDAS patient group (odds ratio, 1.57). When compared to the CS group, AFDAS patients were older, experienced more severe initial strokes, and had similar rates of pre-stroke anticoagulation prescription. Additionally, they demonstrated a higher prevalence of both insular lesions, increased left atrium volume index, reduced ejection fraction, and elevated e/e' ratio. After adjustment, age, initial stroke severity, insular involvement, left atrium volume index, ejection fraction, and e/e' ratio were found to be significant., Conclusions: These results suggest that the right insular cortex lesion on acute stroke may be a cause of AFDAS., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Status epilepticus (SE), a continuous and self-sustaining epileptic seizure lasting more than 30 min, is a neurological emergency that can cause severe brain injuries and increase the risk for the development of epilepsy. Over the past few decades, accumulating evidence has suggested the importance of brain inflammation in the pathogenesis of epilepsy. Honokiol (HNK), a pharmacological activator of sirtuin 3 (SIRT3), is a bioactive compound extracted from the bark or leaves of Magnolia plants that possesses therapeutic benefits for preventing the development of inflammatory injury. However, the therapeutic effects of HNK against epileptic brain injury via regulating molecular mechanisms related to neuroinflammation remains elusive. Therefore, the present study investigated the effects of HNK on pilocarpine-induced status epilepticus (PCSE) and the therapeutic benefits of HNK in regulating inflammatory processes in the hippocampus. Treatment with HNK before PCSE induction attenuated the initiation of behavioral seizures. Post-treatment with HNK after SE onset increased SIRT3 expression, which mitigated glial activation, including reactive astrocytes and activated microglia, in the hippocampus following PCSE. Moreover, HNK treatment reduced the activation of the nuclear factor-κB/nucleotide-binding domain leucine-rich repeat with a pyrin-domain containing 3 inflammasome pathway, thereby inhibiting the production of interleukin-1β pro-inflammatory cytokine, subsequently alleviating PCSE-triggered apoptotic neuronal death in the hippocampus. These results indicate that HNK-induced SIRT3 upregulation has the potential to prevent the progression of epileptic neuropathology through its anti-inflammatory properties. Therefore, the present study suggests that HNK is a natural therapeutic agent for epileptic brain injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Objective: The incidence of facial fractures is on the rise globally, yet limited studies are addressing the diverse forms of facial fractures present in 3D images. In particular, due to the nature of the facial fracture, the direction in which the bone fractures vary, and there is no clear outline, it is difficult to determine the exact location of the fracture in 2D images. Thus, 3D image analysis is required to find the exact fracture area, but it needs heavy computational complexity and expensive pixel-wise labeling for supervised learning. In this study, we tackle the problem of reducing the computational burden and increasing the accuracy of fracture localization by using a weakly-supervised object localization without pixel-wise labeling in a 3D image space., Methods: We propose a Very Fast, High-Resolution Aggregation 3D Detection CAM (VFHA-CAM) model, which can detect various facial fractures. To better detect tiny fractures, our model uses high-resolution feature maps and employs Ablation CAM to find an exact fracture location without pixel-wise labeling, where we use a rough fracture image detected with 3D box-wise labeling. To this end, we extract important features and use only essential features to reduce the computational complexity in 3D image space., Results: Experimental findings demonstrate that VFHA-CAM surpasses state-of-the-art 2D detection methods by up to 20% in sensitivity/person and specificity/person, achieving sensitivity/person and specificity/person scores of 87% and 85%, respectively. In addition, Our VFHA-CAM reduces location analysis time to 76 s without performance degradation compared to a simple Ablation CAM method that takes more than 20 min., Conclusion: This study introduces a novel weakly-supervised object localization approach for bone fracture detection in 3D facial images. The proposed method employs a 3D detection model, which helps detect various forms of facial bone fractures accurately. The CAM algorithm adopted for fracture area segmentation within a 3D fracture detection box is key in quickly informing medical staff of the exact location of a facial bone fracture in a weakly-supervised object localization. In addition, we provide 3D visualization so that even non-experts unfamiliar with 3D CT images can identify the fracture status and location., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 ZIOVISION co. ltd. Published by Elsevier B.V. All rights reserved.)

Background: Recent advancements in cervical interlaminar epidural steroid injections have given rise to the modified paramedian interlaminar (mPIL) approach. The objective of this study was to perform an analysis of the contrast spread pattern within the cervical epidural space, taking into account different needle tip positions in the mPIL approach., Methods: A total of 48 patients were included in the study and randomly assigned to either the medial or lateral group based on the needle tip's position in the anterior-posterior view. The primary outcome measured was the contrast flow under fluoroscopic visualization. As a secondary outcome, we analyzed the location of the needle tip position in both lateral and contralateral oblique views. Clinical effectiveness was assessed by measuring pain intensity and functional disability post-procedure., Results: Significant disparities were noted in the ventral distribution of contrast between the medial and lateral groups. In the lateral images, needle tips in the lateral group were positioned more ventrally compared to those in the medial group. Both groups exhibited statistically significant improvements in neck and radicular pain, as well as functional status, 4 weeks after treatment, with no significant differences between them., Conclusions: Our results suggest that the ventral dispersion of contrast material during cervical interlaminar epidural steroid injections using the mPIL approach may vary depending on the needle tip location., (© 2024 The Author(s). Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

CD45 is a cell surface phosphatase that shapes the T cell receptor signaling threshold but does not have a known ligand. A family of adenovirus proteins, including E3/49K, exploits CD45 to evade immunity by binding to the extracellular domain of CD45, resulting in the suppression of T cell signaling. We determined the cryo-EM structure of this complex and found that the E3/49K protein is composed of three immunoglobulin domains assembled as "beads on a string" that compel CD45 into a closely abutted dimer by cross-linking the CD45 D3 domain, leading to steric inhibition of its intracellular phosphatase activity. Inspired by the E3/49K mechanism, we engineered CD45 surrogate ligands that can fine-tune T cell activation by dimerizing CD45 into different orientations and proximities. The adenovirus E3/49K protein has taught us that, despite a lack of a known ligand, CD45 activity can be modulated by extracellular dimerizing ligands that perturb its phosphatase activity and alter T cell responses.

Despite the success of immune checkpoint blockade (ICB) therapy in various cancers, its efficacy faces challenges in glioblastoma (GBM) due to the immunosuppressive cold-tumor microenvironment. The scarcity of tumor-infiltrating T cells and the suppression of T cell activity significantly limit therapeutic outcomes in GBM. Nitric oxide (NO) and reactive oxygen species (ROS) from tumor-associated myeloid cells (TAMCs) are key contributors to T cell suppression, reducing ICB therapy effectiveness. In this study, we developed NO-ROS scavenging micelles that effectively scavenge both NO and ROS, protecting T cells from their exhausting effects. This leads to a significant increase in T cell infiltration and activation. Moreover, when combined with αPD-1, the survival rate increases to 40 % up to 120 days, enhancing therapeutic efficacy compared to αPD-1 alone. This approach not only protects T cells from the inhibitory effects of NO and ROS but also has the potential to reshape the tumor microenvironment, overcoming T cell suppression in cold tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Adequate postoperative pain management after cesarean section is important for the prognosis of both mother and infant. However, excessive prescription of opioid analgesics has become a concern. This study evaluated the efficacy of local continuous subfascial infusion of ropivacaine in relieving postoperative pain and reducing opioid requirements in postpartum women with cesarean section., Methods: Seventy eligible women undergoing cesarean section were randomly allocated to the ropivacaine and the normal saline group for continuous subfascial wound infiltration. All patients received additional fentanyl through an intravenous patient-controlled analgesia pump. Pain score using the visual analog scale, opioid consumption through pump, and requirements for other analgesics were postoperatively measured within 8 h, 1 day, and 2 days after surgery. Statistical analysis was performed with independent t-tests for continuous variables and Chi-square tests for categorical variables. Paired Wilcoxon and student's t-tests were used for paired samples., Results: Sixty-nine patients (35 in the study and 34 in the control group) were analyzed. The mean VAS scores were lower in the study group all three periods, with significance achieved at day 2 (2.74 ± 0.95 versus 3.41 ± 1.33, p  = 0.028). The intravenous fentanyl consumptions were significantly lower in the study group at all three periods. Total administration of additional non-opioid analgesics including ketorolac, propacetamol, and pethidine was higher in the control group., Conclusions: Continuous subfascial ropivacaine infusion is effective in relieving pain and reducing opioid-based analgesia and other analgesics requirements., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yeon-Hee Kim reports financial support was provided by B. Braun Korea. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: The optimal diameter for endoscopic dilatation of anastomotic strictures after esophagectomy has not been elucidated. This study aimed to determine the optimal target diameter for endoscopic dilatation for anastomotic stricture after esophagectomy., Methods: The medical records of patients who underwent endoscopic dilatation for anastomotic stricture after esophagectomy between January 2009 and June 2024 at Pusan National University Yangsan Hospital were reviewed. The stricture recurrence rate, dilatation-free period, and complications according to the dilatation diameter were collected and included in the analysis., Results: We analyzed 149 endoscopic dilatations (diameters from 10 to 18 mm) in 43 patients. The median follow-up period was 47 months (range, 5-157). The stricture recurrence rate was 72.5%, and the median dilatation-free period was 60 days. The stricture recurrence rate was the lowest (41.7%, p = 0.022), and the overall dilatation-free period was the longest (median 490 days, p = 0.171) in dilations up to 16.5 mm. The stricture recurrence rate was higher in dilations up to 18 mm than in those up to 16.5 mm (54.5% vs. 41.7%, p = 0.331). Moreover, the bleeding rate was higher in patients with dilations up to 18 mm (18.2% vs. 4.2%, p = 0.205)., Conclusion: In patients with anastomotic strictures after esophagectomy, dilation up to 16.5 mm showed a lower stricture recurrence rate, longer dilation-free period, and less postprocedural bleeding than those of dilation up to 18 mm., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Particulate matter (PM) air pollution is associated with an increased incidence of lung diseases, but the underlying mechanisms have not been fully elucidated. In this study, a mouse model of subacute lung inflammation was employed to investigate the cellular responses and gene expression changes induced by exposure to natural ambient air pollution., Methods: C57BL/6J mice were exposed to road dust (primarily PM10) at 150 µg/m³ for 21 days (8 h/day) through a nose-only inhalation exposure system. Lung tissues were analyzed for the expression of proinflammatory signaling, oxidative stress, and fibrosis markers. RNA-sequencing analysis was conducted to identify differentially expressed genes (DEGs). A gene ontology over-representation analysis was performed to identify the altered genetic pathways., Results: Elevated levels of proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, and an increase in phosphorylated MAPK were determined in the road dust exposure group compared to the control group. Histopathological examinations revealed more severe lung inflammation and damage in the exposed mice, including fibrosis and bronchiolar hyperplasia. Gene expression profiling identified 108 DEGs, with decreases in most except genes such as Krt15 and Reg3g. The protein-protein interaction network analysis together with text-mining identified 18 key hub genes, associated with fatty acid oxidation, lipid metabolism, and peroxisomes., Conclusion: This study identified key genes, signaling pathways, and cellular responses in mouse lung affected by road dust exposure. These findings contribute to a deeper understanding of the transcriptional and cellular responses induced by subacute exposure to the PM in road dust.

Sucrose is a desirable component of processed soybean foods and animal feed, and thus, its content is used as an important characteristic for assessing the quality of soybean seeds. However, few studies have focused on the quantitative trait loci (QTLs) associated with sucrose regulation in soybean seeds. This study aims to measure the sucrose content of 1014 soybean accessions and identify genes related to high sucrose levels using QTL analysis. Colorimetric analysis based on the enzymatic reaction of invertase (INV) and glucose oxidase (GOD) was employed to test the germplasms. A total of six high-sucrose genetic resources (IT186230, IT195321, IT263138, IT263276, IT263286, and IT276521) and two low-sucrose genetic resources (IT025668 and IT274054) were identified. Two F 2:3 populations, IT186230 × IT025668 and Ilmi × IT186230, were then established from these germplasms. QTL analysis identified four QTLs ( qSUC6.1 , qSUC11.1 , qSUC15.1 , and qSUC17.1 ), explaining 7.3-27.6% of the phenotypic variation in the sugar content. Twenty candidate genes were found at the four QTLs. Notably, Glyma.17G152300 , located in the qSUC17.1 QTL region, exhibited a 17-fold higher gene expression in the high-sucrose germplasm IT186230 compared to the control germplasm Ilmi, confirming its role as a major gene regulating the sucrose content in soybean. These results may assist in marker-assisted selection for breeding programs that aim to develop soybean lines with a higher sucrose content.

Background: Influenza imposes a significant healthcare burden in Korea, leading the government to initiate a national immunization program. Previous studies on vaccine effectiveness (VE) were limited to single-season estimation in Korea., Methods: This multicenter prospective cohort study enrolled patients with influenza-like illnesses at 10 medical centers in Korea from 2011 to 2021. The demographic and clinical data were collected from questionnaire surveys and electronic medical records. Using a test-negative design, we aimed to investigate the effectiveness of a seasonal influenza vaccine for antigenic matching of the vaccine and circulating viral strains over 10 seasons., Results: Overall, 5322 adults aged ≥65 years were enrolled. Only three (33.3 %) of nine seasons showed >70 % antigenic match between vaccine and circulating strains. Influenza VE was significantly variable by season, ranging from -46.9 % (95 %confidence interval [CI]: -127.6-5.2) in the 2011/12 season to 47.7 % (95 %CI: 22.6-64.7) in the 2016/17 season. A significant difference was observed in the VE depending on whether the vaccine strains matched with epidemic strains: 28.8 % (95 %CI: 8.8-44.8) in matched seasons versus -12.0 % (95 %CI: -30.0-3.7) in mismatched seasons. Across the study period, influenza-related hospitalizations were reduced by 13.6 % (95 %CI: 0.7-24.8) with vaccination. In a subgroup analysis, the VE against influenza-related hospitalization was 48.4 % (95 %CI 29.6-62.2) in A/H3N2 dominant seasons and 53.8 % (95 %CI: -73.4-87.7) in A/H1N1 dominant seasons, respectively., Conclusion: Influenza vaccine mismatch was frequent over the study period, leading to negligibly low VE in mismatched seasons. Influenza vaccination reduces the risk of influenza-related hospitalizations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hee Jin Cheong reports financial support was provided by Korea University College of Medicine. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This study aimed to investigate the association between non-traditional lipid profiles and the risk of 1-year vascular events in patients who were already using statins before stroke and had admission LDL-C < 100 mg/dL. This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with acute ischemic stroke patients who treated with statin before index stroke and LDL-C < 100 mg/dL on admission. Non-traditional lipid profiles including non-HDL, TC/HDL ratio, LDL/HDL ratio, and TG/HDL ratio were analyzed as a continuous or categorical variable. The primary vascular outcome within one year was a composite of recurrent stroke (either hemorrhagic or ischemic), myocardial infarction (MI) and all-cause mortality. Hazard ratios (95% Cis) for 1-year vascular outcomes were analyzed using the Cox PH model for each non-traditional lipid profiles groups. A total of 7028 patients (age 70.3 ± 10.8years, male 59.8%) were finally analyzed for the study. In unadjusted analysis, no significant associations were observed in the quartiles of LDL/HDL ratio and 1-year primary outcome. However, after adjustment of relevant variables, compared with Q1 of the LDL/HDL ratio, Q4 was significantly associated with increasing the risk of 1-year primary outcome (HR 1.48 [1.19-1.83]). For the LDL/HDL ratio, a linear relationship was observed (P for linearity < 0.001). Higher quartiles of the LDL/HDL ratio were significantly and linearly associated with increasing the risk of 1-year primary vascular outcomes. These findings suggest that even during statin therapy with LDL-C < 100 mg/dl on admission, there should be consideration for residual risk based on the LDL/HDL ratio, following stroke., (© 2024. The Author(s).)

In this study, a directional electrode separator (DES) was designed and incorporated into a single-chamber bioelectrochemical system (BES) to reduce migration and reoxidation of hydrogen. This issue arises when H 2 , generated at the cathode, travels to the anode where anodic biofilms use H 2 . To test the feasibility of our design, a 3D-printed BES reactor equipped with a DES was inoculated with anaerobic digestor granules and operated under fed-batch conditions using fermented corn stover effluent. The DES equipped reactor achieved significantly higher current densities (∼53 A/m²) compared to a conventional single-chamber BES without a separator (∼16 A/m²), showing a 3.3 times improvement. Control abiotic electrochemical experiments revealed that the DES exhibited significantly higher proton conductivity (456±127 µS/mm) compared to a proton exchange membrane (67±21 µS/mm) with a statistical significance of P=0.03. The DES also effectively reduced H 2 migration to the anode by 21-fold relative to the control. Overall, incorporating a DES in a single-chamber BES enhanced anodic current density by reducing H 2 migration to the anode., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to investigate the efficacy of ethanol extracts of Cornus alba (ECA) against benign prostatic hyperplasia (BPH) in vitro and in vivo ., Materials and Methods: The prostate stromal cells (WPMY-1) and epithelial cells (RWPE-1) were used to examine the action mechanism of ECA in BPH in vitro . ECA efficacy was evaluated in vivo using a testosterone propionate (TP)-induced BPH rat model., Results: Treatment with ECA inhibited the proliferation of prostate cells by inducing G1-phase cell cycle arrest through the regulation of positive and negative proteins. Treatment of prostate cells with ECA resulted in alterations in the mitogen-activated protein kinases and protein kinase B signaling pathways. The transcriptional binding activity of the NF-κB motif was suppressed in both ECA-treated prostate cells. In addition, treatment with ECA altered the level of BPH-associated axis markers (5α-reductase, fibroblast growth factor-2, androgen receptor, epidermal growth factor, Bcl-2, and Bax) in both cell lines. Finally, the administration of ECA attenuated the enlargement of prostatic tissues in the TP-induced BPH rat model, accompanied by histology, immunoblot, and serum dihydrotestosterone levels., Conclusions: These results demonstrated that ECA exerted beneficial effects on BPH both in vitro and in vivo and might provide valuable information in the development of preventive or therapeutic agents for improving BPH., Competing Interests: The authors have no conflicts to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Anatomical airway labeling is crucial for precisely identifying airways displaying symptoms such as constriction, increased wall thickness, and modified branching patterns, facilitating the diagnosis and treatment of pulmonary ailments. This study introduces an innovative airway labeling methodology, BranchLabelNet, which accounts for the fractal nature of airways and inherent hierarchical branch nomenclature. In developing this methodology, branch-related parameters, including position vectors, generation levels, branch lengths, areas, perimeters, and more, are extracted from a dataset of 1000 chest computed tomography (CT) images. To effectively manage this intricate branch data, we employ an n-ary tree structure that captures the complicated relationships within the airway tree. Subsequently, we employ a divide-and-group deep learning approach for multi-label classification, streamlining the anatomical airway branch labeling process. Additionally, we address the challenge of class imbalance in the dataset by incorporating the Tomek Links algorithm to maintain model reliability and accuracy. Our proposed airway labeling method provides robust branch designations and achieves an impressive average classification accuracy of 95.94% across fivefold cross-validation. This approach is adaptable for addressing similar complexities in general multi-label classification problems within biomedical systems., (© 2024. International Federation for Medical and Biological Engineering.)

Hand hygiene among anesthesia personnel is important to prevent hospital-acquired infections in operating rooms; however, an efficient monitoring system remains elusive. In this study, we leverage a deep learning approach based on operating room videos to detect alcohol-based hand hygiene actions of anesthesia providers. Videos were collected over a period of four months from November, 2018 to February, 2019, at a single operating room. Additional data was simulated and added to it. The proposed algorithm utilized a two-dimensional (2D) and three-dimensional (3D) convolutional neural networks (CNNs), sequentially. First, multi-person of the anesthesia personnel appearing in the target OR video were detected per image frame using the pre-trained 2D CNNs. Following this, each image frame detection of multi-person was linked and transmitted to a 3D CNNs to classify hand hygiene action. Optical flow was calculated and utilized as an additional input modality. Accuracy, sensitivity and specificity were evaluated hand hygiene detection. Evaluations of the binary classification of hand-hygiene actions revealed an accuracy of 0.88, a sensitivity of 0.78, a specificity of 0.93, and an area under the operating curve (AUC) of 0.91. A 3D CNN-based algorithm was developed for the detection of hand hygiene action. The deep learning approach has the potential to be applied in practical clinical scenarios providing continuous surveillance in a cost-effective way., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain., Objective: To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA)., Design: Target trial emulation study., Setting: Nationwide health care data of South Korea obtained from the National Health Insurance Service between 2010 and 2022., Patients: Patients aged 60 years or older who have T2D and are initiating treatment with SGLT2 inhibitors or dulaglutide., Measurements: The primary outcome was the presumed clinical onset of dementia. The date of onset was defined as the year before the date of dementia diagnosis, assuming that the time between the onset of dementia and diagnosis was 1 year. The 5-year risk ratios and risk differences comparing SGLT2 inhibitors with dulaglutide were estimated in a 1:2 propensity score-matched cohort adjusted for confounders., Results: Overall, 12 489 patients initiating SGLT2 inhibitor treatment (51.9% dapagliflozin and 48.1% empagliflozin) and 1075 patients initiating dulaglutide treatment were included. In the matched cohort, over a median follow-up of 4.4 years, the primary outcome event occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group. The estimated risk difference was -0.91 percentage point (95% CI, -2.45 to 0.63 percentage point), and the estimated risk ratio was 0.81 (CI, 0.56 to 1.16)., Limitation: Residual confounding is possible; there was no adjustment for hemoglobin A 1c levels or duration of diabetes; the study is not representative of newer drugs, including more effective GLP-1 RAs; and the onset of dementia was not measured directly., Conclusion: Under conventional statistical criteria, a risk for dementia between 2.5 percentage points lower and 0.6 percentage point greater for SGLT2 inhibitors than for dulaglutide was estimated to be highly compatible with the data from this study. However, whether these findings generalize to newer GLP-1 RAs is uncertain. Thus, further studies incorporating newer drugs within these drug classes and better addressing residual confounding are required., Primary Funding Source: Ministry of Food and Drug Safety of South Korea., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-3220.

Backgruound: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined., Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months., Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background: Minimalist transcatheter aortic valve replacement (TAVR) under monitored anesthesia care (MAC) emphasizes early recovery. Remimazolam is a novel benzodiazepine with a short recovery time. This study hypothesized that remimazolam is non-inferior to dexmedetomidine in terms of recovery after TAVR., Methods: In this retrospective observational study, remimazolam was compared to dexmedetomidine in patients who underwent TAVR under MAC at a tertiary academic hospital between July 2020 and July 2022. The primary outcome was timely recovery after TAVR, defined as discharge from the intensive care unit within the first day following the procedure. Propensity score matching was used to compare timely recovery between remimazolam and dexmedetomidine, applying a non-inferiority margin of -10%., Results: The study included 464 patients, of whom 218 received remimazolam and 246 received dexmedetomidine. After propensity score matching, 164 patients in each group were included in the analysis. Regarding timely recovery after TAVR, remimazolam was non-inferior to dexmedetomidine (152 of 164 [92.7%] in the remimazolam group versus 153 of 164 [93.3%] in the dexmedetomidine group, risk difference [95% CI]: -0.6% [-6.7%, 5.5%]). The use of remimazolam was associated with fewer postoperative vasopressors/inotropes (21 of 164 [12.8%] vs. 39 of 164 [23.8%]) and temporary pacemakers (TPMs) (76 of 164 [46.3%] vs. 108 of 164 [65.9%]) compared to dexmedetomidine., Conclusions: In patients undergoing TAVR under MAC, remimazolam was non-inferior to dexmedetomidine in terms of timely recovery. Remimazolam may be associated with better postoperative recovery profiles, including a lesser need for vasopressors/inotropes and TPMs.

Inflammation-related diseases are often marked by elevated levels of nitric oxide (NO) and reactive oxygen species (ROS), which play important roles in the modulation of inflammation. However, the development of organic materials effective in managing NO/ROS levels has remained a challenge. This study introduces a novel organic compound, NmeGA, engineered to scavenge both NO and ROS. NmeGA ingeniously integrates N-methyl-1,2,-phenylenediamine (Nme), a NO scavenger, with gallic acid (GA), a ROS scavenger, through an amide bond, endowing it with enhanced scavenging capabilities over its individual component. This compound exhibits reduced toxicity and increased lipophilicity value, underlining its increased biological applicability and highlighting its potential as an inflammation management tool. Through in vitro studies on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, NmeGA displayed remarkable scavenging efficiency for NO and ROS, coupled with significant anti-inflammatory effects. In an LPS-induced peritonitis model, administration of NmeGA substantially decreased mortality rates, NO and ROS levels, and inflammatory cytokine concentrations. These findings highlight NmeGA's versatility as a therapeutic agent against various inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To evaluate whether the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors which have shown potential neuroprotective effects, is associated with lower risk of dementia in patients with type 2 diabetes (T2D) and comorbid mental disorders, who are considerably more susceptible to dementia., Methods: Using the nationwide healthcare data of South Korea between 2010 and 2022, we conducted a retrospective cohort study among patients with T2D and comorbid mental disorders initiating SGLT2 inhibitors versus active comparator (Dipeptidyl Peptidase IV (DPP4) inhibitors). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years of incident dementia were estimated after weighting by propensity score fine stratification method., Results: Over a 4.8-year median follow-up, SGLT2 inhibitors were associated with a 12 % lower risk of dementia compared with DPP4 inhibitors (11.31 vs. 12.86 events per 1000 person years; HR 0.88, 95 % CI 0.84 to 0.92; RD -1.55, -2.13 to -0.97). The results were consistent when stratified by age, sex, individual component, severe mental disorders, presence of insulin, history of cardiovascular disease, or history of hypertension., Conclusions: SGLT2 inhibitors versus DPP4 inhibitors were associated with a lower risk of incident dementia in patients with T2D and comorbid mental disorders. Further randomized controlled trials are required to confirm our findings., Competing Interests: Declaration of competing interest All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: this study was funded by the Ministry of Food and Drug Safety, South Korea. JYS received grants from the Ministry of Food and Drug Safety, Ministry of Health and Welfare, National Research Foundation of Korea, and Government-wide R&D Fund for Infectious Disease Research and Pharmaceutical Companies, including Pfizer, LG Chemical, and Union Chimique Belge. BH was supported by China Scholarship Council (Grant no. #202,308,260,057). YMC received research grants from Daewoong Pharmaceuticals and Sanofi, and consultation fees from Hanmi and LG Chemical. The other authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

There is a growing need to develop artificial intelligence technologies capable of accurately predicting the properties of materials. This necessitates the expansion of material databases beyond the scope of density functional theory, and also the development of deep learning (DL) models that can be effectively trained with a limited amount of high-fidelity data. We developed a DL model utilizing a crystal structure representation based on the orbital field matrix (OFM), which was modified to incorporate information on elemental properties and valence electron configurations. This model, effectively capturing the interrelation between the elemental properties in the crystal, was coined the PRoperty-networking Orbital Field maTrix-convolutional neural Network (PROFiT-Net). Remarkably, PROFiT-Net demonstrated high accuracy in predicting the dielectric constant, experimental band gaps, and formation enthalpies compared with other leading DL models. Moreover, our model accurately identifies physical patterns, such as avoiding the prediction of unphysical negative band gaps and exhibiting a Penn-model-like trend while maintaining the scalability. We envision that PROFiT-Net will accelerate the development of functional materials.

USP11 is overexpressed in colorectal cancer (CRC) and breast cancer tissues compared to normal tissues, suggesting a role in promoting cell proliferation and inhibiting cell death. In this study, we observed that depleting USP11 inhibits cell proliferation and delays cell cycle progression. This depletion leads to increased p53 protein levels due to an extended half-life, resulting in elevated p21 mRNA levels in a p53-dependent manner. The rise in p53 protein upon USP11 depletion is linked to a reduced half-life of MDM2, a known E3 ligase for p53, via enhanced polyubiquitination of MDM2. These findings indicate that USP11 might act as a deubiquitinase for MDM2, regulating the MDM2-p53-p21 axis. Additionally, USP11 depletion promotes the induction of senescent cells in a manner dependent on its deubiquitinase activity. Our findings provide insights into the physiological significance of high USP11 expression in primary tumors and its reduction in senescent cells, highlighting its potential as a therapeutic target., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mantidis Ootheca (sangpiaoxiao), the egg case of the mantis, is a type of insect-derived traditional medicine widely used in East Asia. However, species identification based on egg morphology is challenging, leading to the distribution of counterfeit and adulterated products. The use of inauthentic ingredients can pose serious health risks to consumers. This study aimed to develop PCR markers that can rapidly and accurately differentiate between authentic and counterfeit Mantidis Ootheca. The mitochondrial cytochrome c oxidase I (COI) region was sequenced in thirteen samples from four mantis species: Tenodera angustipennis , Statilia maculata , Hierodula patellifera , and T. sinensis . Four sets of SCAR primers were designed based on species-specific nucleotide polymorphisms, and a multiplex SCAR assay was developed by combining all sets of the primers. The sequence-characterized amplified region (SCAR) primers successfully produced amplicons for each target species, even with low-DNA templates or templates containing DNA from multiple samples. No amplification was observed for nontarget species. This study presents a novel approach for identifying authentic Mantidis Ootheca species using DNA-based diagnostic marker assays, which enable rapid and precise species identification. The SCAR assays developed in this study will aid in maintaining quality control and promoting the standardization of commercial Mantidis Ootheca products.

Background/Objectives : Geriatric hip fracture patients have an increased risk of malnutrition. Proper nutritional supply in the perioperative period is very important for their recovery. Oral nutritional supplements (ONSs) are recommended in geriatric hip fracture patients to improve dietary intake and prevent complications. This study aimed to evaluate the efficacy of postoperative ONSs after total hip arthroplasty in geriatric hip fracture patients. Methods : A retrospective study of elderly patients who underwent total hip arthroplasty for hip fracture was conducted. Data from patients who received ONSs postoperatively until hospital discharge (ONS group, n = 69) were compared with patients who did not receive ONSs (control group, n = 168). Laboratory test results, including serum protein and albumin levels, length of hospital stay, and the incidence of postoperative medical complications of the two groups, were analyzed. Results : Preoperative serum protein and albumin levels were significantly higher in the control group ( p = 0.002 and p = 0.010, respectively). However, the degree of decline for both protein and albumin levels was significantly less in the ONS group ( p < 0.001 for both). Serum albumin levels were significantly higher in the ONS group at postoperative two-week follow-up ( p = 0.006). The length of hospital stay was shorter in the ONS group ( p < 0.001). The incidence of postoperative delirium was significantly higher in the control group ( p = 0.007). Conclusions : In geriatric hip fracture patients, postoperative ONSs can improve postoperative nutritional status, shorten the length of hospital stay, and reduce the incidence of postoperative delirium.

Engineering biomimetic tissue implants with human induced pluripotent stem cells (hiPSCs) holds promise for repairing volumetric tissue loss. However, these implants face challenges in regenerative capability, survival, and geometric scalability at large-scale injury sites. Here, we present scalable vessel-integrated muscle-like lattices (VMLs), containing dense and aligned hiPSC-derived myofibers alongside passively perfusable vessel-like microchannels inside an endomysium-like supporting matrix using an embedded multimaterial bioprinting technology. The contractile and millimeter-long myofibers are created in mechanically tailored and nanofibrous extracellular matrix-based hydrogels. Incorporating vessel-like lattice enhances myofiber maturation in vitro and guides host vessel invasion in vivo, improving implant integration. Consequently, we demonstrate successful de novo muscle formation and muscle function restoration through a combinatorial effect between improved graft-host integration and its increased release of paracrine factors within volumetric muscle loss injury models. The proposed modular bioprinting technology enables scaling up to centimeter-sized prevascularized hiPSC-derived muscle tissues with custom geometries for next-generation muscle regenerative therapies., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Effective interventions for overall healthy subjects with mild cognitive impairment are currently limited. Choline alphoscerate (alpha glyceryl phosphorylcholine, αGPC) is a choline-containing phospholipid used to treat cognitive function impairments in specific neurological conditions. This study aimed to investigate the efficacy and safety of αGPC in individuals diagnosed with mild cognitive impairment., Methods: In this multicenter, randomized, placebo-controlled trial, 100 study subjects with mild cognitive impairment underwent a double-blind SHCog™ soft capsule (600 mg αGPC) or placebo treatment for 12 weeks. The primary efficacy outcome included changes from baseline on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Safety assessments included regular monitoring of adverse events, and clinical laboratory tests were conducted at baseline and the end of the trial., Results: After 12 weeks of αGPC treatment, the ADAS-cog score decreased by 2.34 points, which was significantly greater than the change observed in the placebo group. No serious AEs were reported, and no study subjects discontinued the intervention because of AEs. There was no significant difference in incidence rate of AEs between the αGPC group and the placebo group., Conclusion: This study suggests that αGPC is a safe and effective intervention for improving cognitive function in study subjects with mild cognitive impairment., Trial Registration: Clinical Research Information Service; Osong (Chungcheongbuk-do): Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); KCT0008797; A 12-week, multicenter, randomized, double-blind, placebo-controlled human application study to evaluate the efficacy and safety of SH&#95;CAPK08 on cognitive function improvement in mild cognitive decline., (© 2024. The Author(s).)

Background: Delirium affects up to 50% of patients following high-risk surgeries and is associated with poor long-term prognosis. This study employed machine learning to predict delirium using polysomnography (PSG) and sleep-disorder questionnaire data, and aimed to identify key sleep-related factors for improved interventions and patient outcomes. Methods: We studied 912 adults who underwent surgery under general anesthesia at a tertiary hospital (2013-2024) and had PSG within 5 years of surgery. Delirium was assessed via clinical diagnoses, antipsychotic prescriptions, and psychiatric consultations within 14 days postoperatively. Sleep-related data were collected using PSG and questionnaires. Machine learning predictions were performed to identify postoperative delirium, focusing on model accuracy and feature importance. Results: This study divided the 912 patients into an internal training set (700) and an external test set (212). Univariate analysis identified significant delirium risk factors: midazolam use, prolonged surgery duration, and hypoalbuminemia. Sleep-related variables such as fewer rapid eye movement (REM) episodes and higher daytime sleepiness were also linked to delirium. An extreme gradient-boosting-based classification task achieved an AUC of 0.81 with clinical variables, 0.60 with PSG data alone, and 0.84 with both, demonstrating the added value of PSG data. Analysis of Shapley additive explanations values highlighted important predictors: surgery duration, age, midazolam use, PSG-derived oxygen saturation nadir, periodic limb movement index, and REM episodes, demonstrating the relationship between sleep patterns and the risk of delirium. Conclusions: The artificial intelligence model integrates clinical and sleep variables and reliably identifies postoperative delirium, demonstrating that sleep-related factors contribute to its identification. Predicting patients at high risk of developing postoperative delirium and closely monitoring them could reduce the costs and complications associated with delirium.

Background: Appropriate hospital-to-home transitional care has been recognized for its positive impact on health care usage and health outcomes in patients with COPD. However, there is limited research assessing its effects on patient-centered outcomes, focusing on patient symptoms and experiences., Methods: This single-blind randomized controlled trial included subjects diagnosed with COPD at one of 2 university hospitals in South Korea. The study included 179 subjects (transitional care group [transitional care], 87; usual care group [usual care], 92). The transitional care received transitional care comprising post-discharge care planning, personalized education, breathing exercises, telephone counseling, home visits, and referral to social services. We analyzed the effects of these interventions by comparing breathing symptoms and various patient-centered outcomes between the 2 groups., Results: The Modified Medical Research Council scores (mean [SD], transitional care 1.3 [1.06], usual care 1.82 [1.1], P = .002) and COPD Assessment Test scores (transitional care 6.32 [5.5], usual care 9.43 [7.16], P = .001) in the intervention group demonstrated more significant improvement than did those in the usual care. Following intervention, the subjects exhibited enhanced awareness of their disease, an increased frequency of inhaler use (transitional care 49.69 [1.67], usual care 46.86 [7.92], P = .002), and lower depression and anxiety scores. Additionally, the transitional care outperformed the usual care in the domain of subject experience during hospitalization (transitional care 39.34 [6.14], usual care 37.5 [5.61], P = .036), preparedness before discharge (transitional care 34.54 [4.96], usual care 32.3 [5.09], P = .003), and post-discharge management (transitional care 34.72 [4.36], usual care 30.29 [4.26], P = .003)., Conclusions: Evidence-based transitional care services can exert positive effects on patient-centered indices. Our findings can be used as evidence of the need to establish patient-centered transitional care as a form of universal care for patients with COPD., (Copyright © 2024 by Daedalus Enterprises.)

Background  Capsular contracture of breast implants is a major complication in breast surgery. Clinically, covering a breast implant with acellular dermal matrix (ADM) or autologous tissue is considered to be the most effective technique to prevent capsular contracture. This study was designed to compare the protective effects of ADM and latissimus dorsi (LD) muscle flap placement on capsular contracture by increasing the rate of capsular contracture through controlled radiation exposure in a rabbit model. Methods  Twenty New Zealand white rabbits were divided into three groups. After the implant was placed beneath the pectoralis major muscle, the lateral third of the implant was left exposed in the control group ( n  = 6). In the ADM group ( n  = 7), the exposed implant was covered with AlloDerm. In the LD flap group ( n  = 7), the exposed implant was covered with a pedicled LD muscle flap. All groups were irradiated 3 weeks after implant insertion. After 6 months, peri-implant tissues were harvested and analyzed. Results  ADM showed markedly lower myofibroblast activity than the LD flap. However, transforming growth factor-β1 levels and the activity of collagen types I and III produced in fibroblasts were significantly lower in the ADM group than in the LD flap group. Conclusion  Based on the findings of our rabbit experiments, ADM is expected to have a comparative advantage in reducing the risk of capsular contracture compared to the LD flap., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are pivotal in combating coronavirus disease 2019 (COVID-19); however, the declining antibody titers postvaccination pose challenges for sustained protection and herd immunity. Although gut microbiome is reported to affect the early antibody response after vaccination, its impact on the longevity of vaccine-induced antibodies remains unexplored., Methods: A prospective cohort study was conducted involving 44 healthy adults who received two doses of either the BNT162b2 or ChAdOx1 vaccine, followed by a BNT162b2 booster at six months. The gut microbiome was serially analyzed using 16S rRNA and shotgun sequencing, while humoral immune response was assessed using a SARS-CoV-2 spike protein immunoassay., Results: Faecalibacterium prausnitzii was associated with robust and persistent antibody responses post-BNT162b2 vaccination. In comparison, Escherichia coli was associated with a slower antibody decay following ChAdOx1 vaccination. The booster immune response was correlated with metabolic pathways involving cellular functions and aromatic amino acid synthesis., Conclusions: The findings of this study underscored the potential interaction between the gut microbiome and the longevity/boosting effect of antibodies following vaccination against SARS-CoV-2. The identification of specific microbial associations suggests the prospect of microbiome-based strategies for enhancing vaccine efficacy., (© 2024. The Author(s).)

Periodontitis, a prevalent chronic inflammatory disease caused by bacteria, poses a significant challenge to current treatments by merely slowing their progression. Herein, we propose an innovative solution in the form of hierarchical nanostructured 3D printed bilayer membranes that serve as dual-drug delivery nanoplatforms and provide scaffold function for the regeneration of periodontal tissue. Nanocomposite hydrogels were prepared by combining lipid nanoparticle-loaded grape seed extract and simvastatin, as well as chitin nanocrystals, which were then 3D printed into a bilayer membrane that possesses antimicrobial properties and multiscale porosity for periodontal tissue regeneration. The constructs exhibited excellent mechanical properties by adding chitin nanocrystals and provided a sustained release of distinct drugs over 24 days. We demonstrated that the bilayer membranes are cytocompatible and have the ability to induce bone-forming markers in human mesenchymal stem cells, while showing potent antibacterial activity against pathogens associated with periodontitis. In vivo studies further confirmed the efficacy of bilayer membranes in enhancing alveolar bone regeneration and reducing inflammation in a periodontal defect model. This approach suggests promising avenues for the development of implantable constructs that not only combat infections, but also promote the regeneration of periodontal tissue, providing valuable insights into advanced periodontitis treatment strategies.

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively. Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques. There has been a decrease in intravenous thrombolysis rates, from 12% in 2017-2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for non-cardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

WNT signaling is fundamental in development and homeostasis, but how the Frizzled receptors (FZDs) propagate signaling remains enigmatic. Here, we present the cryo-EM structure of FZD4 engaged with the DEP domain of Dishevelled 2 (DVL2), a key WNT transducer. We uncover a distinct binding mode where the DEP finger-loop inserts into the FZD4 cavity to form a hydrophobic interface. FZD4 intracellular loop 2 (ICL2) additionally anchors the complex through polar contacts. Mutagenesis validates the structural observations. The DEP interface is highly conserved in FZDs, indicating a universal mechanism by which FZDs engage with DVLs. We further reveal that DEP mimics G-protein/β-arrestin/GRK to recognize an active conformation of receptor, expanding current GPCR engagement models. Finally, we identify a distinct FZD4 dimerization interface. Our findings delineate the molecular determinants governing FZD/DVL assembly and propagation of WNT signaling, providing long-sought answers underlying WNT signal transduction., (© 2024. The Author(s).)

For most shoulder surgeons, addressing massive rotator cuff tears that have retracted ends poses a significant challenge. This study introduces a technique, termed the "sandwich augmentation technique," which incorporates the long head of the biceps tendon (LHBT) into a single-row rotator cuff repair. The procedure, performed arthroscopically with the patient in the lateral decubitus position, involves attaching the LHBT and rotator cuff tissues together to the greater tuberosity. This effectively sandwiches them within the rotator cuff footprint. The goal of this technique is to enhance the thickness of the fully interposed cuff margin, thereby providing better support for the repair. The sandwich augmentation technique, which integrates the biceps into the rotator cuff repair, has demonstrated positive clinical outcomes and moderate anatomical results. It also prevents superior migration of the humeral head in cases of large or massive rotator cuff tears. Further research is required to assess the long-term effectiveness of this procedure.

Objectives: To determine whether balanced solutions can reduce the incidence of acute kidney injury after off-pump coronary artery bypass surgery compared with saline., Design: Randomized controlled trial., Setting: Single tertiary care center., Participants: Patients who underwent off-pump coronary artery bypass surgery between June 2014 and July 2020., Interventions: Balanced solution-based chloride-restrictive intravenous fluid strategy., Measurements and Main Results: The primary outcome was acute kidney injury within 7 postoperative days, as defined by the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline. The incidence of acute kidney injury was 4.4% (8/180) in the balanced group and 7.3% (13/178) in the saline group. The difference was not statistically significant (risk difference, -2.86%; 95% confidence interval [CI], -7.72% to 2.01%; risk ratio, 0.61, 95% CI, 0.26 to 1.43; p = 0.35). Compared with the balanced group, the saline group had higher levels of intraoperative serum chloride and lower base excess, which resulted in a lower pH., Conclusions: In patients undergoing off-pump bypass surgery with a normal estimated glomerular filtration rate, the intraoperative balanced solution-based chloride-restrictive intravenous fluid administration strategy did not decrease the rate of postoperative acute kidney injury compared with the saline-based chloride-liberal intravenous fluid administration strategy., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Acute gastroenteritis (AGE) is a common cause of pediatric morbidity and mortality worldwide. AGE can cause an imbalance in the intestinal microbiota. This study aimed to investigate the diversity of the gut microbiome in Korean children hospitalized for infectious AGE at a university hospital., Methods: A total of 23 stool samples from patients aged 5 months to 11 years with AGE were analyzed. Thirteen convalescent stool samples were collected 1 month after discharge. Multiplex polymerase chain reaction (PCR) for the five viruses and 16 bacteria-specific AGE pathogens (PowerChek Multiplex Real time PCR Kit, Seoul, Korea), and 16s rRNA sequencing (Illumina MiSeq Sequencing system, Illumina, USA) were performed., Results: According to the results of multiplex PCR for causative pathogens, the microbiome taxonomic profile (MTP) of the gut microbiome in three groups of AGE, norovirus AGE (n = 11), Campylobacter AGE (n = 7) and Salmonella AGE (n = 5) was compared. The phylum Actinobacteria was significantly more abundant in the norovirus AGE (P = 0.011), whereas the phylum Proteobacteria was significantly more abundant in Salmonella AGE (P = 0.012). Alpha diversity, which indicates species richness and diversity, showed no statistical differences. However, beta diversity, representing the similarity in MTP between norovirus, Campylobacter, and Salmonella AGE, was significantly different (P = 0.007). In convalescence, compared with their corresponding AGE samples, the phylum Firmicutes; and the lower taxa Christensenellaceae (P = 0.0152) and Lachnospiraceae (P = 0.0327) were significantly increased., Conclusions: In pediatric AGE, the type of infectious agent can affect the diversity and dominance of gut microbiota in pediatric patients. Furthermore, healthy gut bacteria increased during the period of 1 month after infection, allowing a return to a healthy state without causing long-term dysbiosis., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

The roles of brain asymmetry in Drosophila are diverse, encompassing the regulation of behavior, the creation of memory, neurodevelopment, and evolution. A comprehensive examination of the Drosophila brain has the potential to enhance our understanding of the functional significance of brain asymmetry in cognitive and behavioral processes, as well as its role in evolutionary perspectives. This study explores the influence of brain asymmetry on interval timing behaviors in Drosophila, with a specific focus on the asymmetric body (AB) structure. Despite being bilaterally symmetric, the AB exhibits functional asymmetry and is located within the central complex of the fly brain. Interval timing behaviors, such as rival-induced prolonged mating duration: longer mating duration behavior (LMD) and sexual experience-mediated shorter mating duration behavior (SMD), are essential for Drosophila. We utilize genetic manipulations to selectively activate or inhibit AB neurons and evaluates their impact on LMD and SMD behaviors. The results indicate that specific populations of AB neurons play unique roles in orchestrating these interval timing behaviors. Notably, inhibiting GAL4 R38D01 -labeled AB neurons disrupts both LMD and SMD, while GAL4 R42C09 neuron inhibition affects only LMD. Moreover, hyperexcitation of GAL4 R72A10 -labeled AB neurons perturbs SMD. Our study identifies NetrinB (NetB) and Abdominal-B (Abd-B) are important genes for AB neurons in LMD and highlights the role of 5-HT1B neurons in generating LMD through peptidergic Pigment-dispersing factor (PDF) signaling. In summary, this study underscores the importance of AB neuron asymmetry in mediating interval timing behaviors and provides insights into the underlying mechanisms of memory formation and function in Drosophila., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: The appropriate follow-up surveillance strategy for patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) remains unknown., Objective: To assess clinical outcomes in patients with and without ACS who have undergone high-risk PCI according to a follow-up strategy of routine stress testing at 12 months after PCI vs standard care alone., Design, Setting, and Participants: The POST-PCI (Pragmatic Trial Comparing Symptom-Oriented vs Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention) trial was a randomized clinical trial that compared follow-up strategies of routine functional testing vs standard care alone 12 months after high-risk PCI. Patients were categorized as presenting with or without ACS. Patients were enrolled in the trial from November 2017 through September 2019, and patients were randomized from 11 sites in South Korea; data analysis was performed in 2022., Intervention: Patients categorized as presenting with or without ACS were randomized to either a routine functional testing or standard care alone follow-up strategy 12 months after high-risk PCI., Main Outcomes and Measures: The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years following randomization. Kaplan-Meier event rates through 2 years and Cox model hazard ratios (HRs) were generated, and interactions were tested., Results: Of 1706 included patients, 350 patients (20.5%) were female, and the mean (SD) patient age was 64.7 (10.3) years. In total, 526 patients (30.8%) presented with ACS. Compared with those without ACS, patients with ACS had a 55% greater risk of the primary outcome (HR, 1.55; 95% CI, 1.03-2.33; P = .03) due to higher event rates in the first year. The 2-year incidences of the primary outcome were similar between strategies of routine functional testing or standard care alone in patients with ACS (functional testing: 16 of 251 [6.6%]; standard care: 23 of 275 [8.5%]; HR, 0.76; 95% CI, 0.40-1.44; P = .39) and in patients without ACS (functional testing: 30 of 598 [5.1%]; standard care: 28 of 582 [4.9%]; HR, 1.04; 95% CI, 0.62-1.74; P = .88) (P for interaction for ACS = .45). Although a landmark analysis suggested that the rates of invasive angiography and repeat revascularization were higher after 1 year in the routine functional testing group, the formal interactions between ACS status and either invasive angiography or repeat revascularization were not significant., Conclusion and Relevance: Despite being at higher risk for adverse clinical events in the first year after PCI than patients without ACS, patients with ACS who had undergone high-risk PCI did not derive incremental benefit from routine surveillance stress testing at 12 months compared with standard care alone during follow-up., Trial Registration: ClinicalTrials.gov Identifier: NCT03217877.

Erythema nodosum (EN) is a skin manifestation of panniculitis characterized by symmetric, painful, tender nodules, and most cases are self-limiting. Few cases of EN following Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination have been reported, and they are generally self-limiting. We reported the challenging case of a 63-year-old Asian woman with EN that persisted for more than three months after a coronavirus disease-19 (COVID-19). There was no improvement despite topical steroid and NSAIDs treatment, and the patient was successfully treated with combination of high-dose steroid and NSAIDs. There were long-lasting symptoms involving various organ symptoms persisting over three months after COVID-19, which is known as Long COVID. As part of Long COVID, there are limited cases of skin manifestations. Given that immune dysregulation due to persistent coronaviruses may contribute to refractory EN, Erythema nodosum related to COVID-19 is rare, but can occur; clinicians should be aware of the occurrence of EN following COVID-19 infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)