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Abstract 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.

Abstract To investigate long-term outcomes and develop a risk model for pathological multi–station N2 (pN2b) in patients who underwent upfront surgery for clinical single–station N2 (cN2a) non–small cell lung cancer (NSCLC). From 2006 to 2018, 547 patients who had upfront surgery for suspected cN2a NSCLC underwent analysis. A risk model for predicting pN2b metastasis was developed using preoperative clinical variables via multivariable logistic analysis. Among 547 clinical cN2a NSCLC patients, 118 (21.6%), 58 (10.6%), and 371 (67.8%) had pN0, pN1, and pN2. Among 371 pN2 NSCLC patients, 77 (20.8%), 165 (44.5%), and 129 (34.7%) had pN2a1, pN2a2, and pN2b. The 5-year overall survival rates for pN2a1 and pN2a2 were significantly higher than for pN2b (p = 0.041). Histologic type (p

Abstract Backgrounds Limited data are available on racial differences in the clinical features of chronic bronchitis (CB) patients with chronic obstructive pulmonary disease (COPD). In this study, we aimed to compare clinical features among CB patients of different races. We also analyzed the clinical significance of CB, defined classically and based on the COPD Assessment Test (CAT), to validate the CAT-based definition. Methods We analyzed patient data extracted from the Korean COPD Subgroup Study (KOCOSS) cohort (2012–2021) and US Genetic Epidemiology of COPD (COPDGene) study (2008–2011). We compared clinical characteristics among CB and non-CB patients of three different races using two CB definitions. Results In this study, 3,462 patients were non-Hispanic white (NHW), 1,018 were African American (AA), and 1,793 were Asian. The proportions of NHW, AA, and Asian patients with CB according to the classic definition were 27.4%, 20.9%, and 10.7%, compared with 25.2%, 30.9%, and 23.0% according to the CAT-based definition, respectively. The risk of CB prevalence was highest in NHW and lowest in Asian COPD patients. Among all races, CB patients were more likely to be current smokers, have worse respiratory symptoms and poorer health-related quality of life (HrQoL), and to have decreased lung function and exercise capacity. Most of these characteristics showed similar associations with the outcomes between the two definitions of CB. A binominal regression model revealed that CB patients of all races had an increased risk of future exacerbations according to both CB definitions, except for Asian patients with classically defined CB. Conclusions The presence of CB was associated with worse respiratory symptoms, HrQoL, exercise capacity and lung function, and more exacerbations, regardless of race or CB definition. The CAT-based definition may be more useful for assessing the risk of future exacerbations in Asian COPD patients.

Abstract Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

Abstract Ferroelectric (FE) field-effect transistors are interesting for their non-destructive readout characteristic and energy efficiency but are difficult to integrate on silicon platforms. Here, FE ZrXAl1−XOY (ZAO) is demonstrated by compressive strain in contact with ZnO. The metal-ferroelectric-semiconductor-metal capacitor exhibits a substantial remnant polarization of 15.2 µC cm−2, along with a bowknot-like anti-clockwise hysteresis in the capacitance curves. The FE-ZAO gated ZnO thin-film transistor presents a large memory window (3.84 V), low subthreshold swing (55 mV dec−1), high ION/IOFF ratio (≈108), and low off-state current (≈1 pA). The grazing incidence X-ray diffraction and scanning transmission electron microscopy analyses reveal the ferroelectric rhombohedral phase (space group R3m) in the nanocrystal ZAO, containing an angle of ≈71.7° between the [111] and [11-1] directions with d 111 -spacing of 3.037 Å and d 11-1 -spacing of 2.927 Å. Finally, the memory and neuromorphic applications are analyzed by demonstrating multi-level memory and synaptic weight performance with a high learning accuracy of 91.82%.

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.

Abstract Electrochemical nitrogen reduction reaction (NRR) is a sustainable alternative to the Haber‒Bosch process for ammonia (NH3) production. However, the significant uphill energy in the multistep NRR pathway is a bottleneck for favorable serial reactions. To overcome this challenge, we designed a vanadium oxide/nitride (V2O3/VN) hybrid electrocatalyst in which V2O3 and VN coexist coherently at the heterogeneous interface. Since single‐phase V2O3 and VN exhibit different surface catalytic kinetics for NRR, the V2O3/VN hybrid electrocatalyst can provide alternating reaction pathways, selecting a lower energy pathway for each material in the serial NRR pathway. As a result, the ammonia yield of the V2O3/VN hybrid electrocatalyst was 219.6 µg h−1 cm−2, and the Faradaic efficiency was 18.9%, which is much higher than that of single‐phase VN, V2O3, and VNxOy solid solution catalysts without heterointerfaces. Density functional theory calculations confirmed that the composition of these hybrid electrocatalysts allows NRR to proceed from a multistep reduction reaction to a low‐energy reaction pathway through the migration and adsorption of intermediate species. Therefore, the design of metal oxide/nitride hybrids with coherent heterointerfaces provides a novel strategy for synthesizing highly efficient electrochemical catalysts that induce steps favorable for the efficient low‐energy progression of NRR.

Abstract The advanced patterning process is the basis of integration technology to realize the development of next-generation high-speed, low-power consumption devices. Recently, area-selective atomic layer deposition (AS-ALD), which allows the direct deposition of target materials on the desired area using a deposition barrier, has emerged as an alternative patterning process. However, the AS-ALD process remains challenging to use for the improvement of patterning resolution and selectivity. In this study, we report a superlattice-based AS-ALD (SAS-ALD) process using a two-dimensional (2D) MoS2-MoSe2 lateral superlattice as a pre-defining template. We achieved a minimum half pitch size of a sub-10 nm scale for the resulting AS-ALD on the 2D superlattice template by controlling the duration time of chemical vapor deposition (CVD) precursors. SAS-ALD introduces a mechanism that enables selectivity through the adsorption and diffusion processes of ALD precursors, distinctly different from conventional AS-ALD method. This technique facilitates selective deposition even on small pattern sizes and is compatible with the use of highly reactive precursors like trimethyl aluminum. Moreover, it allows for the selective deposition of a variety of materials, including Al2O3, HfO2, Ru, Te, and Sb2Se3.

Mitochondrial stress and the dysregulated mitochondrial unfolded protein response (UPRmt) are linked to various diseases, including metabolic disorders, neurodegenerative diseases, and cancer. Mitokines, signaling molecules released by mitochondrial stress response and UPRmt, are crucial mediators of inter-organ communication and influence systemic metabolic and physiological processes. In this review, we provide a comprehensive overview of mitokines, including their regulation by exercise and lifestyle interventions and their implications for various diseases. The endocrine actions of mitokines related to mitochondrial stress and adaptations are highlighted, specifically the broad functions of fibroblast growth factor 21 and growth differentiation factor 15, as well as their specific actions in regulating inter-tissue communication and metabolic homeostasis. Finally, we discuss the potential of physiological and genetic interventions to reduce the hazards associated with dysregulated mitokine signaling and preserve an equilibrium in mitochondrial stress-induced responses. This review provides valuable insights into the mechanisms underlying mitochondrial regulation of health and disease by exploring mitokine interactions and their regulation, which will facilitate the development of targeted therapies and personalized interventions to improve health outcomes and quality of life.

As coronavirus disease-2019 (COVID-19) becomes an endemic disease, the virus continues to evolve and become immunologically distinct from previous strains. Immune imprinting has raised concerns about bivalent mRNA vaccines containing both ancestral virus and Omicron variant. To increase efficacy against the predominant strains as of the second half of 2023, the updated vaccine formulation contained only the mRNA of XBB.1.5 sublineage. We conducted a multicenter, test-negative, case-control study to estimate XBB.1.5 monovalent vaccine effectiveness (VE) and present the results of an interim analysis with data collected in November 2023. Patients who underwent COVID-19 testing at eight university hospitals were included and matched based on age (19-49, 50-64, and ≥65 years) and sex in a 1:1 ratio. VE was calculated using the adjusted odds ratio derived from multivariable logistic regression. Of the 992 patients included, 49 (5.3%) received the XBB.1.5 monovalent vaccine at least 7 days before COVID-19 testing. Patients with COVID-19 (cases) were less likely to have received the XBB.1.5 monovalent vaccine (case 3.5% vs. control 7.2%, p=0.019) and to have a history of COVID-19 within 6 months (2.2% vs. 4.6%, p=0.068). In contrast, patients with COVID-19 were more likely to be healthcare workers (8.2% vs. 3.0%, p=0.001) and to have chronic neurological diseases (16.7% vs. 11.9%, p=0.048). The adjusted VE of the XBB.1.5 monovalent mRNA vaccine was 56.8% (95% confidence interval: 18.7-77.9%). XBB.1.5 monovalent mRNA vaccine provided significant protection against COVID-19 in the first one to two months after vaccination.

BackgroundThe assessment of long-term humoral and cellular immunity post-vaccination is crucial for establishing an optimal vaccination strategy.MethodsThis prospective cohort study evaluated adults (≥18 years) who received a BA.4/5 bivalent vaccine. We measured the anti-receptor binding domain immunoglobulin G antibody and neutralizing antibodies (NAb) against wild-type and Omicron subvariants (BA.5, BQ.1.1, BN.1, XBB.1 and EG.5) up to 9 months post-vaccination. T-cell immune responses were measured before and 4 weeks after vaccination.ResultsA total of 108 (28 SARS-CoV-2-naïve and 80 previously infected) participants were enrolled. Anti-receptor binding domain immunoglobulin G (U/mL) levels were higher at 9 months post-vaccination than baseline in SAR-CoV-2-naïve individuals (8,339 vs. 1,834, p

This study aimed to determine the correlation of the parameters that indicate the status of the ocular surface with the prognosis of corneal opacification. Fifty dogs (96 eyes) were examined using a grid-line illuminator (non-invasive tear film break-up time (NIBUT)). Thirty dogs (54 eyes) were included in the final analysis based on the criteria. The NIBUT and tear film break-up time (TFBUT) results of the eyes included in the study were divided into three groups: Group 1 (< 5 s), Group 2 (5 to 5 s in the grid-line illumination plate NIBUT test. Among NIBUT, STT-1, and TFBUT, NIBUT was the only test that showed significant associations with the changes in COS.

Abstract Background The Center for Personalized Precision Medicine of Tuberculosis (cPMTb) was constructed to develop personalized pharmacotherapeutic systems for tuberculosis (TB). This study aimed to introduce the cPMTb cohort and compare the distinct characteristics of patients with TB, non-tuberculosis mycobacterium (NTM) infection, or latent TB infection (LTBI). We also determined the prevalence and specific traits of polymorphisms in N-acetyltransferase-2 (NAT2) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) phenotypes using this prospective multinational cohort. Methods Until August 2021, 964, 167, and 95 patients with TB, NTM infection, and LTBI, respectively, were included. Clinical, laboratory, and radiographic data were collected. NAT2 and SLCO1B1 phenotypes were classified by genomic DNA analysis. Results Patients with TB were older, had lower body mass index (BMI), higher diabetes rate, and higher male proportion than patients with LTBI. Patients with NTM infection were older, had lower BMI, lower diabetes rate, higher previous TB history, and higher female proportion than patients with TB. Patients with TB had the lowest albumin levels, and the prevalence of the rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 39.2%, 48.1%, and 12.7%, respectively. The prevalence of rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 42.0%, 44.6%, and 13.3% for NTM infection, and 42.5%, 48.3%, and 9.1% for LTBI, respectively, which did not differ significantly from TB. The prevalence of the normal, intermediate, and lower transporter SLCO1B1 phenotypes in TB, NTM, and LTBI did not differ significantly; 74.9%, 22.7%, and 2.4% in TB; 72.0%, 26.1%, and 1.9% in NTM; and 80.7%, 19.3%, and 0% in LTBI, respectively. Conclusions Understanding disease characteristics and identifying pharmacokinetic traits are fundamental steps in optimizing treatment. Further longitudinal data are required for personalized precision medicine. Trial registration This study registered ClinicalTrials.gov NO. NCT05280886.

Abstract Background Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient‘s groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test. Methods On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides. Results The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response. Conclusions Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.

Background: The optimal choice of valve substitute for aortic valve replacement (AVR) in pediatric patients remains a matter of debate. This study investigated the outcomes following AVR using mechanical prostheses in children. Methods: Forty-four patients younger than 15 years who underwent mechanical AVR from March 1990 through March 2023 were included. The outcomes of interest were death or transplantation, hemorrhagic or thromboembolic events, and reoperation after mechanical AVR. Adverse events included any death, transplant, aortic valve reoperation, and major thromboembolic or hemorrhagic event. Results: The median age and weight at AVR were 139 months and 32 kg, respectively. The median follow-up duration was 56 months. The most commonly used valve size was 21 mm (14 [31.8%]). There were 2 in-hospital deaths, 1 in-hospital transplant, and 1 late death. The overall survival rates at 1 and 10 years post-AVR were 92.9% and 90.0%, respectively. Aortic valve reoperation was required in 4 patients at a median of 70 months post-AVR. No major hemorrhagic or thromboembolic events occurred. The 5- and 10-year adverse event-free survival rates were 81.8% and 72.2%, respectively. In univariable analysis, younger age, longer cardiopulmonary bypass time, and smaller valve size were associated with adverse events. The cut-off values for age and prosthetic valve size to minimize the risk of adverse events were 71 months and 20 mm, respectively. Conclusion: Mechanical AVR could be performed safely in children. Younger age, longer cardiopulmonary bypass time and smaller valve size were associated with adverse events. Thromboembolic or hemorrhagic complications might rarely occur.

Abstract In radiomics research, the issue of different instruments being used is significant. In this study, we compared three correction methods to reduce the batch effects in radiogenomic data from fluorodeoxyglucose (FDG) PET/CT images of lung cancer patients. Texture features of the FDG PET/CT images and genomic data were retrospectively obtained. The features were corrected with different methods: phantom correction, ComBat method, and Limma method. Batch effects were estimated using three analytic tools: principal component analysis (PCA), the k-nearest neighbor batch effect test (kBET), and the silhouette score. Finally, the associations of features and gene mutations were compared between each correction method. Although the kBET rejection rate and silhouette score were lower in the phantom-corrected data than in the uncorrected data, a PCA plot showed a similar variance. ComBat and Limma methods provided correction with low batch effects, and there was no significant difference in the results of the two methods. In ComBat- and Limma-corrected data, more texture features exhibited a significant association with the TP53 mutation than in those in the phantom-corrected data. This study suggests that correction with ComBat or Limma methods can be more effective or equally as effective as the phantom method in reducing batch effects.

Abstract Background F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is useful in multiple myeloma (MM) for initial workup and treatment response evaluation. Herein, we evaluated the prognostic value of semi-quantitative FDG parameters for predicting the overall survival (OS) of MM patients with or without autologous stem cell transplantation (ASCT). Methods Study subjects comprised 227 MM patients who underwent baseline FDG PET/CT. Therein, 123 underwent ASCT while 104 did not. Volumes of interest (VOIs) of bones were drawn on CT images using a threshold of 150 Hounsfield units. FDG parameters of maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and number of focal lesions (FLs) were measured. Kaplan-Meier survival analysis with log-rank tests and Cox proportional hazards regression analyses were performed for overall survival (OS). Results In the ASCT cohort, R-ISS stage, MTV, and TLG were associated with survival. In the non-ASCT cohort, however, R-ISS stage was not associated with patient outcomes. In contrast, high SUVmax, SUVmean, MTV, TLG, and FL could predict worse OS (hazard ratio [HR] = 2.569, 2.649, 2.506, 2.839, and 1.988, respectively). Importantly, combining FDG parameters with R-ISS stage provided a new risk classification system that discriminated worse OS in the non-ASCT cohort significantly better than did R-ISS stage alone. Conclusions In the non-ASCT cohort, semi-quantitative FDG parameters were significant predictors of worse OS. Furthermore, combining FDG parameters with R-ISS stage may provide a new risk staging system that can better stratify the survival of MM patients without ASCT.

Abstract Background To discuss the first case of mitomycin C (MMC) toxicity after XEN® gel stent implantation in a glaucoma patient, conducted using the XEN “air” technique with an ophthalmic viscosurgical device (OVD). Case presentation A 44-year-old Asian male presented with increased intraocular pressure (IOP; 52 mmHg) accompanied by keratic precipitates and an edematous cornea. He was diagnosed with uveitic glaucoma in the left eye, and the IOP was controlled with a topical anti-glaucoma agent. However, glaucoma progression was revealed by Humphrey visual field (HVF) and optical coherence tomography (OCT) examinations. The patient underwent uneventful XEN gel stent implantation using the XEN air technique and an MMC (0.02%, 0.1 mL) injection, with subconjunctival air and OVD injection provided prior to XEN implantation in the left eye. The patient exhibited a decreased IOP (11 mmHg), elevated bleb, and extensive subconjunctival hemorrhage on postoperative day 1. On postoperative day 18, diffuse conjunctival injection and a large avascular bleb was noticed around the XEN gel stent. The patient complained of severe eye pain and discomfort, suggestive of MMC toxicity, and the IOP was 12 mmHg. The patient was treated with a topical steroid and antibiotics tapered over a 6-month period. Finally, the toxicity was successfully controlled, with the IOP stabilizing at around 15 mmHg. Conclusions Although significantly greater lowering of the IOP can be expected with the use of subconjunctival OVD injection and MMC during XEN gel stent implantation, a cautious approach and a longer monitoring period are required.

Abstract Background Efforts have been made to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations using a variety of measures. Broncho-Vaxom (BV) is an immunomodulating agent that has shown potential benefit by balancing between immune stimulation and regulation in patients with COPD. In this study, we evaluated the clinical efficacy of BV for reducing the risk of COPD exacerbations. Methods This study was based on the Korean National Health Insurance database, which contains reimbursement information for almost the entire population of South Korea. We extracted data from 2016 to 2019 for patients started on BV during 2017–2018. We collected baseline data on demographics, comorbidities, inhaler use, hospital type, and insurance type 1 year before starting BV. We also analyzed exacerbation history, starting from the year before BV initiation. Results In total, 238 patients were enrolled in this study. Their mean age was 69.2 ± 9.14 years, 79.8% were male, and 45% experienced at least one exacerbation. BV reduced the risk of moderate (odds ratio [OR] = 0.59, 95% confidence interval [CI]: 0.38–0.91) and moderate-to-severe exacerbations compared to pre- and post-BV (OR = 0.571, 95% CI: 0.37–0.89). BV use also reduced the incidence of moderate and moderate-to-severe exacerbations (incidence rate ratio [IRR] = 0.75, p = 0.03; and IRR = 0.77, p = 0.03, respectively). The use of BV was significantly delayed moderate exacerbations (hazard ratio = 0.68, p = 0.02), but not with moderate-to-severe or severe exacerbations. Conclusion The use of BV was associated with fewer moderate and moderate-to-severe exacerbations. Additionally, BV was associated with a delay in moderate COPD exacerbations.

The aim of our retrospective study is to develop and assess an imaging-based model utilizing 18F-FDG PET parameters for predicting the five-year survival in non-small-cell lung cancer (NSCLC) patients after curative surgery. A total of 361 NSCLC patients who underwent curative surgery were assigned to the training set (n = 253) and the test set (n = 108). The LASSO regression model was used to construct a PET-based risk score for predicting five-year survival. A hybrid model that combined the PET-based risk score and clinical variables was developed using multivariate logistic regression analysis. The predictive performance was determined by the area under the curve (AUC). The individual features with the best predictive performances were co-occurrence_contrast (AUC = 0.675) and SUL peak (AUC = 0.671). The PET-based risk score was identified as an independent predictor after adjusting for clinical variables (OR 5.231, 95% CI 1.987–6.932; p = 0.009). The hybrid model, which integrated clinical variables, significantly outperformed the PET-based risk score alone in predictive accuracy (AUC = 0.771 vs. 0.696, p = 0.022), a finding that was consistent in the test set. The PET-based risk score, especially when integrated with clinical variables, demonstrates good predictive ability for five-year survival in NSCLC patients following curative surgery.

Abstract Background Cold ischemia‐reperfusion injury (IRI) is an unavoidable complication of kidney transplantation. We investigated the role of regulatory T cells (Treg) in cold IRI and whether the interleukin (IL)‐2/anti‐IL‐2 antibody complex (IL‐2C) can ameliorate cold IRI. Methods We developed a cold IRI mouse model using kidney transplantation and analyzed the IL‐2C impact on cold IRI in acute, subacute and chronic phases. Results Treg transfer attenuated cold IRI, while Treg depletion aggravated cold IRI. Next, IL‐2C administration prior to IRI mitigated acute renal function decline, renal tissue damage and apoptosis and inhibited infiltration of effector cells into kidneys and pro‐inflammatory cytokine expression on day 1 after IRI. On day 7 after IRI, IL‐2C promoted renal regeneration and reduced subacute renal damage. Furthermore, on day 28 following IRI, IL‐2C inhibited chronic fibrosis. IL‐2C decreased reactive oxygen species‐mediated injury and improved antioxidant function. When IL‐2C was administered following IRI, it also increased renal regeneration with Treg infiltration and suppressed renal fibrosis. In contrast, Treg depletion in the presence of IL‐2C eliminated the positive effects of IL‐2C on IRI. Conclusion Tregs protect kidneys from cold IRI and IL‐2C inhibited cold IRI by increasing the renal Tregs, suggesting a potential of IL‐2C in treating cold IRI. Key Points Interleukin (IL)‐2/anti‐IL‐2 antibody complex attenuated acute renal injury, facilitated subacute renal regeneration and suppressed chronic renal fibrosis after cold ischemia‐reperfusion injury (IRI) by increasing the renal Tregs. IL‐2/anti‐IL‐2 antibody complex decreased reactive oxygen species‐mediated injury and improved antioxidant function. This study suggests the therapeutic potential of the IL‐2/anti‐IL‐2 antibody complex in kidney transplantation‐associated cold IR.

Background: Data on the durability of booster dose immunity of COVID-19 vaccines are relatively limited. Methods: Immunogenicity was evaluated for up to 9–12 months after the third dose of vaccination in 94 healthy adults. Results: Following the third dose, the anti-spike immunoglobulin G (IgG) antibody response against the wild-type was boosted markedly, which decreased gradually over time. However, even 9–12 months after the booster dose, both the median and geometric mean of anti-spike IgG antibody levels were higher than those measured 4 weeks after the second dose. Breakthrough infection during the Omicron-dominant period boosted neutralizing antibody titers against Omicron sublineages (BA.1 and BA.5) and the ancestral strain. T-cell immune response was efficiently induced and maintained during the study period. Conclusions: mRNA vaccine booster dose elicited durable humoral immunity for up to 1 year after the third dose and T-cell immunity was sustained during the study period, supporting an annual COVID-19 vaccination strategy.

Summary: Background: Lung cancer diagnostic guidelines advocate for invasive mediastinal nodal staging (IMNS), but the survival benefits of this approach in patients with non-small cell lung cancer (NSCLC) without radiologic evidence of lymph node metastasis (rN0) remain uncertain. We aimed to investigate the impact of IMNS in patients with rN0 NSCLC by comparing the long-term survival between patients who underwent IMNS and those who did not (non-IMNS). Methods: In this retrospective cohort study, we included patients with NSCLC but without radiologic evidence of lymph node metastasis from the Registry for Thoracic Cancer Surgery and the clinical data warehouse at the Samsung Medical Centre, Republic of Korea between January 2, 2008 and December 31, 2016. We compared the 5-year overall survival (OS) rate as the primary outcome after propensity score matching between the IMNS and non-IMNS groups. The age, sex, performance statue, tumor size, centrality, solidity, lung function, FDG uptake in PET-CT, and histological examination of the tumor before surgery were matched. Findings: A total of 4545 patients (887 in the IMNS group and 3658 in the non-IMNS group) who received curative treatment for NSCLC were included in this study. By the mediastinal node dissection, the overall incidence of unforeseen mediastinal node metastasis (N2) was 7.2% (317/4378 patients). Despite the IMNS, 67% of pathological N2 was missed (61/91 patients with unforeseen N2). Based on propensity score matching, 866 patients each for the IMNS and non-IMNS groups were assigned. There was no significant difference in 5-year OS and recurrence-free survival (RFS) between two groups: 5-year OS was 73.9% (95% confidence interval, CI: 71%–77%) for IMNS and 71.7% (95% CI: 68.6%–74.9%; p = 0.23), for non-IMNS (hazard ratio, HR 0.90, 95% CI: 0.77–1.07), while 5-year RFS was 64.7% (95% CI: 61.5%–68.2%) and 67.5% (95% CI: 64.3%–70.9%; p = 0.35 (HR 1.08, 95% CI: 0.92–1.27), respectively. Moreover, the timing and locations of recurrence were similar in both groups. Interpretation: IMNS might not be required before surgery for patients with NSCLC without LN suspicious of metastasis. Further randomised trials are required to validate the findings of the present study. Funding: None.

IntroductionPhysical activity has significant positive effects on health. Accelerometers can be used to track daily physical activity. The Fitbit Inspire 3 is a commercially available health and fitness tracker, but its validity for tracking steps among individuals with transtibial amputation has not been examined. Therefore, the purpose of this study was to evaluate the concurrent validity of the Fitbit Inspire 3 for assessing free-living daily steps in adults with transtibial amputation.MethodsParticipants (n = 79) completed a general health survey and were provided with a Fitbit Inspire 3 and activPAL 3 accelerometer to wear concurrently for seven days in their home environment. Relationships between the activPAL and Fitbit Inspire 3 were examined using Pearson's Correlation. Paired samples t-tests, mean difference, mean absolute difference, and equivalence testing were used to compared daily step counts between Fitbit Inspire 3 and activPAL 3.ResultsAverage step counts were 5,768 ± 3,750 (mean ± SD) and 4,674 ± 3,081 by the Fitbit Inspire 3 and activPAL, respectively. A high correlation (r = 0.93) but significant mean difference was found between the activPAL 3 and Fitbit Inspire 3 (p

ABSTRACTAntimicrobial resistance (AMR) in pathogenic bacteria poses a significant threat to public health, yet there is still a need for development in the tools to deeply understand AMR genes based on genetic or structural information. In this study, we present an interactive web database named Blanket Overarching Antimicrobial-Resistance gene Database with Structural information (BOARDS, sbml.unist.ac.kr), a database that comprehensively includes 3,943 reported AMR gene information for 1,997 extended spectrum beta-lactamase (ESBL) and 1,946 other genes as well as a total of 27,395 predicted protein structures. These structures, which include both wild-type AMR genes and their mutants, were derived from 80,094 publicly available whole-genome sequences. In addition, we developed the rapid analysis and detection tool of antimicrobial-resistance (RADAR), a one-stop analysis pipeline to detect AMR genes across whole-genome sequencing (WGSs). By integrating BOARDS and RADAR, the AMR prevalence landscape for eight multi-drug resistant pathogens was reconstructed, leading to unexpected findings such as the pre-existence of the MCR genes before their official reports. Enzymatic structure prediction-based analysis revealed that the occurrence of mutations found in some ESBL genes was found to be closely related to the binding affinities with their antibiotic substrates. Overall, BOARDS can play a significant role in performing in-depth analysis on AMR.IMPORTANCEWhile the increasing antibiotic resistance (AMR) in pathogen has been a burden on public health, effective tools for deep understanding of AMR based on genetic or structural information remain limited. In this study, a blanket overarching antimicrobial-resistance gene database with structure information (BOARDS)—a web-based database that comprehensively collected AMR gene data with predictive protein structural information was constructed. Additionally, we report the development of a RADAR pipeline that can analyze whole-genome sequences as well. BOARDS, which includes sequence and structural information, has shown the historical landscape and prevalence of the AMR genes and can provide insight into single-nucleotide polymorphism effects on antibiotic degrading enzymes within protein structures.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common foodborne pathogen which is frequently used as the reference strain for Salmonella. Investigating the sigma factor network and protomers is crucial to understand the genomic and transcriptomic properties of the bacterium. Its promoters were identified using various methods such as dRNA-seq, ChIP-chip, or ChIP-Seq. However, validation using ChIP-exo, which exhibits higher-resolution performance compared to conventional ChIP, has not been conducted to date. In this study, using the representative strain S. Typhimurium LT2 (LT2), the ChIP-exo experiment was conducted to accurately determine the binding sites of catalytic RNA polymerase subunit RpoB and major sigma factors (RpoD, RpoN, RpoS, and RpoE) during exponential phase. Integrated with the results of RNA-Seq, promoters and sigmulons for the sigma factors and their association with RpoB have been discovered. Notably, the overlapping regions among binding sites of each alternative sigma factor were found. Furthermore, comparative analysis with Escherichia coli str. K-12 substr. MG1655 (MG1655) revealed conserved binding sites of RpoD and RpoN across different species. In the case of small RNAs (sRNAs), 50 sRNAs observed their expression during the exponential growth of LT2. Collectively, the integration of ChIP-exo and RNA-Seq enables genome-scale promoter mapping with high resolution and facilitates the characterization of binding events of alternative sigma factors, enabling a comprehensive understanding of the bacterial sigma factor network and condition-specific active promoters.

Abstract Various memristive devices have been proposed for use in neuromorphic computing systems as artificial synapses. Analog synaptic devices with linear conductance updates during training are efficiently essential to train neural networks. Although many different analog memristors have been proposed, a more reliable approach to implement analog synaptic devices is needed. In this study, we propose the memristor of a Cu/SiOx/implanted a-SiGex/p++ c-Si structure containing an a-Si layer with properly controlled conductance through Ge implantation. The a-SiGex layer plays a multifunctional role in device operation by limiting the current overshoot, confining the heat generated during operation and preventing the silicide formation reaction between the active metal (Cu) and the Si bottom electrode. Thus, the a-SiGex interface layer enables the formation of multi-weak filaments and induces analog switching behaviors. The TEM observation shows that the insertion of the a-SiGex layer between SiOx and c-Si remarkably suppresses the formation of copper silicide, and reliable set/reset operations are secured. The origin of the analog switching behaviors is discussed by analyzing current-voltage characteristics and electron microscopy images. Finally, the memristive-neural network simulations show that our developed memristive devices provide high learning accuracy and are promising in future neuromorphic computing hardware.

Abstract We retrospectively evaluate the actual anterior–posterior (AP) corneal radius ratio in eyes with previous laser correction for myopia (M-LVC) according to axial length (AL) using biometry data exported from swept-source optical coherence tomography between January 2018 and October 2021 in a tertiary hospital (1018 eyes with a history of M-LVC and 19,841 control eyes). The AP ratio was significantly higher in the LVC group than in the control group. Further, it was significantly positively correlated with AL in the LVC group. We also investigated the impact of the AP ratio, AL and keratometry (K) on the absolute prediction error (APE) in 39 eyes that underwent cataract surgery after M-LVC. In linear regression analyses, there were significant correlations between APE and AL/TK, while APE and AP ratio had no correlation. The APE was significantly lower in the Barrett True-K with total keratometry (Barrett True-TK) than in the Haigis-L formula on eyes with AL above 26 mm and K between 38 and 40 D. In conclusion, in eyes with previous M-LVC, AP ratio increases with AL. The Barrett True-K or Barrett True-TK formulas are recommended rather than Haigis-L formula in M-LVC eyes with AL above 26 mm and K between 38 and 40D.

Abstract Background To evaluate the efficacy of 1% and 2% rebamipide clear solution in the treatment of dry eye disease (DED). Methods Two hundred twenty patients with DED were randomly assigned to one of three groups: the 1% rebamipide, 2% rebamipide, or placebo (eye drops containing the same ingredients, except for the active components). Each eye drop was instilled four times daily for 12 weeks. Changes in tear film break-up time (TBUT), corneal and conjunctival staining score, Schirmer 1 test, and the Ocular Surface Disease Index (OSDI) from baseline to 12-week visit between the study groups were compared for efficacy assessment. Results The mean age of study patients was 43.8±14.2 years. The 1% and 2% rebamipide groups showed greater improvement in TBUT (1.99±1.87 and 2.02±2.21 s) at 12 weeks from baseline than the placebo group (1.25±2.93 s). The 2% rebamipide group showed greater improvement in the corneal staining score (− 3.15±2.00) at 12 weeks from baseline than the placebo group (− 2.85±1.80). The 1% and 2% rebamipide groups showed improvement in Schirmer 1 test (1.27±3.86 and 1.50±4.14 mm) at 12 weeks of treatment, but not the placebo group (0.55±2.99 mm). Both the rebamipide groups and the placebo group showed significantly improved OSDI after treatment for 12 weeks; however, there was no significant difference among the three groups. Conclusions 1% and 2% rebamipide clear solutions are an effective therapeutic option for improving TBUT and tear volume, and stabilizing the corneal staining score in DED.

Abstract Lead‐acid batteries (LABs) are widely used as a power source in many applications due to their affordability, safety, and recyclability. However, as the demand for better electrochemical energy storage increases in various fields, there is a growing need for more advanced battery technologies. To meet this need, the application of LABs in hybrid electric vehicles and renewable energy storage has been explored, and the development of lead–carbon batteries (LCBs) has garnered significant attention as a promising solution. LCBs incorporate carbon materials in the negative electrode, successfully addressing the negative irreversible sulfation issue that plagues traditional LABs. Composite material additives and Pb–C composite electrodes have also gained popularity as effective ways to enhance negative electrode performance. This review article focuses on the role of carbon additives in the negative electrode of LCBs and discusses potential future additives that may be incorporated into the development of LCBs. Overall, this article provides insights into the potential of LCBs to offer more efficient and reliable energy storage.

Abstract Background Technetium-99 m 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) and technetium-99 m sodium pyrophosphate (PYP) are the two most commonly used radiotracers for cardiac amyloidosis (CA), but no studies have directly compared them. Therefore, in this study, we directly compared the diagnostic and clinical utility of DPD and PYP scintigraphy in patients with CA. Methods Ten patients with CA were enrolled. Eight clinical variables and 12 scintigraphic parameters were used. Clinical variables were age, sex, estimated glomerular filtration rate (eGFR), N-terminal pro brain natriuretic peptide (NT-proBNP), and the results of electromyography (EMG), a sensory test, electrocardiogram, and echocardiography (EchoCG). Four heart retention ratios (heart/whole-body profile, heart/pelvis, heart/skull, and heart/contralateral lung) were calculated from the DPD and PYP scans and two visual scoring systems (Perugini and Dorbala systems) were used. Comparative analyses were performed between radiotracers and between visual scoring systems using clinical variables and scintigraphic parameters. Results Twenty DPD parameters and nine PYP parameters had significant associations with age, eGFR, NT-proBNP, EchoCG, and EMG. DPD parameters had more frequent significant associations with clinical variables than PYP parameters. Compared to visual scores in the DPD scan, the proportion of patients with higher visual scores in the PYP scan was relatively greater than those with lower visual scores, and there were more patients with a visual score of 2 or higher in PYP scans than DPD scans. Conclusions DPD scintigraphy may reflect the disease severity of CA better than PYP scintigraphy, whereas PYP scintigraphy may be a more sensitive imaging modality for identifying CA involvement.

Bronchiectasis, which is characterized by irreversibly damaged and dilated bronchi, causes significant symptoms, poor quality of life, and increased economic burden and mortality rates. Despite its increasing prevalence and clinical significance, bronchiectasis was previously regarded as an orphan disease, and ideal treatment of this disease has been poorly understood. The European Respiratory Society and British Thoracic Society have recently published guidelines to assist physicians in the clinical field. Guidelines and reports suggest comprehensive management that includes both non-pharmacological and pharmacological treatment. Physiotherapy and pulmonary rehabilitation are two of the most important non-pharmacologic therapies in bronchiectasis patients; long-term inhaled antibiotics and macrolide therapy have gained significant evidence in reducing exacerbation risk in frequent exacerbators. In this review, we summarize recent updates on bronchiectasis treatment to prevent exacerbation and manage clinical deterioration.

Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 μg/mL of DS-Cav1 and SC-TM showed high coefficients of determination (r > 0.90), respectively. Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r = 0.90) and SC-TM (r = 0.86). Further, both antigens showed high precision (coefficient of variation < 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM, but not with the attachment (G) protein.

Coronavirus disease 2019 (COVID-19) is a highly contagious zoonotic respiratory disease with many similarities to influenza. Effective vaccines are available for both; however, rapid viral evolution and waning immunity make them virtually impossible to eradicate with vaccines. Thus, the practical goal of vaccination is to reduce the incidence of serious illnesses and death. Three years after the introduction of COVID-19 vaccines, the optimal vaccination strategy in the endemic period remains elusive, and health authorities worldwide have begun to adopt various approaches. Herein, we propose a COVID-19 vaccination strategy based on the data available until early 2024 and discuss aspects that require further clarification for better decision making. Drawing from comparisons between COVID-19 and influenza vaccination strategies, our proposed COVID-19 vaccination strategy prioritizes high-risk groups, emphasizes seasonal administration aligned with influenza vaccination campaigns, and advocates the co-administration with influenza vaccines to increase coverage.

This is a cross-sectional serosurveillance study for RSV. Between June and September of 2021, a total of 150 sera were collected from 30 individuals in each age group (

Purpose: This study aims to evaluate the impact of South Korea’s national insurance coverage (NIC) expansion and the addition of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. Materials and Methods: A retrospective review was conducted at the Samsung Medical Center (SMC), dividing patients into three groups: pre-NIC expansion, post-NIC expansion, and post-extra genetic counselor involvement. The number of BRCA1/2 tests performed and the detection rates among newly diagnosed and follow-up patients, particularly focusing on triple-negative breast cancer (TNBC) cases, were analyzed. Results: Post-NIC expansion, there was a significant increase in BRCA1/2 testing rates, with a gradual rise in detection rates while maintaining statistical significance. TNBC patients under 60 experienced substantial increases in testing rates. The number of follow-up patients recalled for testing also rose significantly after the extra genetic counselor involvement. Additionally, NIC expansion increased insurance coverage for TNBC patients, enhancing accessibility to testing. Conclusion: The study highlights the positive impact of NIC expansion and genetic counselor involvement on BRCA1/2 mutation testing rates and subsequent patient management. Addressing financial barriers to testing and incorporating genetic counseling significantly improve patient outcomes. This model provides a potential strategy for enhancing early detection and personalized treatment for breast cancer patients with BRCA1/2 mutations, contributing to global cancer management efforts.

Abstract Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) is widely used for management of nasopharyngeal carcinoma (NPC). Combining the radiomic features of pre- and post-treatment FDG PET images may improve tumor characterization and prognostic predication. We investigated prognostic value of radiomic features from pre- and post-radiotherapy FDG PET images in patients with NPC. Quantitative radiomic features of primary tumors were extracted from the FDG PET images of 145 NPC patients and the delta values were also calculated. The study population was divided randomly into two groups, the training and test sets (7:3). A random survival forest (RSF) model was adopted to perform analyses of progression-free survival (PFS) and overall survival (OS). There were 37 (25.5%) cases of recurrence and 16 (11.0%) cases of death during a median follow-up period of 54.5 months. Both RSF models with clinical variables and radiomic PET features for PFS and OS showed comparable predictive performance to RSF models with clinical variables and conventional PET parameters. Tumoral radiomic features of pre- and post-treatment FDG PET and the corresponding delta values may predict PFS and OS in patients with NPC.

Abstract F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a robust imaging modality used for staging multiple myeloma (MM) and assessing treatment responses. Herein, we extracted features from the FDG PET/CT images of MM patients using an artificial intelligence autoencoder algorithm that constructs a compressed representation of input data. We then evaluated the prognostic value of the image-feature clusters thus extracted. Conventional image parameters including metabolic tumor volume (MTV) were measured on volumes-of-interests (VOIs) covering only the bones. Features were extracted with the autoencoder algorithm on bone-covering VOIs. Supervised and unsupervised clustering were performed on image features. Survival analyses for progression-free survival (PFS) were performed for conventional parameters and clusters. In result, supervised and unsupervised clustering of the image features grouped the subjects into three clusters (A, B, and C). In multivariable Cox regression analysis, unsupervised cluster C, supervised cluster C, and high MTV were significant independent predictors of worse PFS. Supervised and unsupervised cluster analyses of image features extracted from FDG PET/CT scans of MM patients by an autoencoder allowed significant and independent prediction of worse PFS. Therefore, artificial intelligence algorithm–based cluster analyses of FDG PET/CT images could be useful for MM risk stratification.

Abstract The beginning of human immunodeficiency virus (HIV) infection treatment depends on various factors, which are significantly correlated with the initial CD4 cell number. However, a covariate correlation between these factors may not reflect the correct outcome variable. Thus, we evaluated the effects of a combination of fixed factors (reduced dimensions), which determine when to start treatment for the first time, on short-term outcome, long-term outcome, and survival, considering correlations between factors. Multiple correspondence analysis was performed on variables obtained from 925 patients who participated in a Korean HIV/acquired immunodeficiency syndrome cohort study (2006–2017). Five reduced dimension groups were derived according to clinical data, viral load, CD4 cell count at diagnosis, initial antiretroviral therapy, and others. The dimension group with high initial viral loads (55,000 copies/mL) and low CD4 cell counts ( 350 cells/mm3) that did not require immediate treatment according to previous guidelines had a higher failure rate for long-term relative CD4 recovery. Our results highlight the importance of early diagnosis and treatment to positively influence long-term disease outcomes, even if the initial immune status is poor, given the patient’s combination of early diagnostic symptoms.

Background: Comorbidities of chronic obstructive pulmonary disease (COPD) influence clinical characteristics and prognosis. Objectives: This study compared the clinical characteristics and exacerbation rate of COPD according to the presence of depression or anxiety. Design: This study used data from The Korea COPD Subgroup Study (KOCOSS) cohort, a nationwide prospective cohort from 54 medical centers, between April 2012 and 2019. Methods: Depression and anxiety were diagnosed with the Beck Depression Inventory and Beck Anxiety Inventory. Negative binomial regression analysis was performed to analyze the frequency of exacerbations in depressed patients and anxiety. Differences in lung function trajectory according to presence of depression/anxiety were analyzed using a linear mixed model. Results: In all, 2147 patients were enrolled. Depressed patients or anxiety had lower lung function, higher modified Medical Research Council (mMRC) grade, St. George Respiratory Questionnaire (SGRQ) score, and COPD assessment test score, and higher rates of exacerbation in the past year than those without depression/anxiety. Depressed patients had a higher frequency of moderate to severe exacerbations [Incidence Rate Ratio (IRR): 1.57, CI: 1.17–2.11, p = 0.002] and those with anxiety had higher frequencies of moderate to severe (IRR: 1.52, CI: 1.03–2.27, p = 0.038) and severe exacerbations (IRR: 2.13, CI: 1.09–4.15, p = 0.025) during 1-year follow-up compared to those without these comorbidities. The differences in the change in annual forced expiratory volume in 1 seconds (FEV 1 ) over 3 years according to the presence of depression or anxiety were not statistically significant. Conclusion: Depressed and anxious patients showed increased respiratory symptoms and exacerbation rate as well as reduced health-related quality of life, whereas there were no significant differences in changes in lung function between groups with and without depression/anxiety.