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Lung cancer remains a major global health problem because of its high cancer-related mortality rate despite advances in therapeutic approaches. Non-small cell lung cancer (NSCLC), a major subtype of lung cancer, is more amenable to surgical intervention in its early stages. However, the prognosis for advanced NSCLC remains poor, owing to limited treatment options. This underscores the growing need for novel therapeutic strategies to complement existing treatments and improve patient outcomes. In recent years, pentacyclic triterpenoids, a group of natural compounds, have emerged as promising candidates for cancer therapy due to their anticancer properties. Pentacyclic triterpenoids, such as lupeol, betulinic acid, betulin, oleanolic acid, ursolic acid, glycyrrhetinic acid, glycyrrhizin, and asiatic acid, have demonstrated the ability to inhibit cell proliferation and angiogenesis, induce apoptosis, suppress metastasis, and modulate inflammatory and immune pathways in NSCLC cell line models. These compounds exert their effects by modulating important signaling pathways such as NF-κB, PI3K/Akt, and MAPK. Furthermore, advances in drug delivery technologies such as nanocarriers and targeted delivery systems have improved the bioavailability and therapeutic efficacy of triterpenoids. However, despite promising preclinical data, rigorous clinical trials are needed to verify their safety and efficacy. This review explores the role of triterpenoids in NSCLC and therapeutic potential in preclinical models, focusing on their molecular mechanisms of action. [ABSTRACT FROM AUTHOR]

Introduction: Microcystis aeruginosa (M. aeruginosa), one of the most prevalent blue-green algae in aquatic environments, produces microcystin by causing harmful algal blooms (HAB). This study investigated the combined effects of nutrients and cyanobacterial subpopulation competition on synthesizing microcystin-LR. Method: In varied nitrogen and phosphorus concentrations, cyanobacterial coculture, and algicidal DCMU presence, the growth was monitored by optical density analysis or microscopic counting, and the microcystin production was analyzed using high-performance liquid chromatography-UV. Furthermore, growth and toxin production were predicted using MATLAB. Results and discussion: First, coculturing with a fast-growing cyanobacterium Synechococcus elongatus UTEX 2973 (S. elongatus) reduced M. aeruginosa biomass and microcystin production at 30oC. Under high nitrogen and low phosphorus conditions, S. elongatus is mostly effective, with up to 94.7% and 92.4% limitation of M. aeruginosa growth and toxin synthesis, respectively. Second, this biological strategy became less effective at 23oC, where S. elongatus grew slower. Third, photosynthesis inhibitor DCMU (3-(3,4-dichlorophenyl)-1,1-dimethylurea) hindered M. aeruginosa growth (at 0.1 mg/L) and microcystin production (at 0.02 mg/L). DCMU was also effective for controlling microcystin production in S. elongatus – M. aeruginosa cocultures. Based on experimental results, a multi-substrate, multi-species kinetic model was built to describe coculture growth and population interactions. Conclusion: Future research should examine more complex models to further develop and refine to facilitate the derivation of more effective recommendations for health prevention programs, particularly for mothers and girls. [ABSTRACT FROM AUTHOR]

This paper proposes a DEVS (Discrete Event System Specification) formalism-based approach to analyze Clock Domain Crossing (CDC) issues in digital circuit design. As modern System on Chip (SoC) designs increasingly integrate multiple clock domains, the verification of CDC-related metastability becomes more challenging and costly. While conventional EDA tools offer solutions for CDC analysis, they often involve substantial computational resources and licensing costs. We present a DEVS-based simulation framework that leverages its inherent advantages in time management and modular structuring to model and analyze CDC scenarios. The framework includes a CDC synchronizer model implemented within the HDL partially compatible DEVS environment, enabling precise analysis of metastability violations based on setup time and hold time requirements. Circuit designers or related engineers can potentially solve timing issues such as CDC by incorporating DEVS-based analysis tools into the design pipeline. [ABSTRACT FROM AUTHOR]

This study evaluates the cooling effects of small-scale water features and fog systems in Sangju Namsan Park, South Korea, focusing on their impact on thermal comfort. While previous studies have demonstrated the potential of urban parks in reducing temperatures, studies on small-scale interventions that examine their effects on thermal comfort and analyze microclimate data collected in specific areas are limited. This study collected and analyzed microclimate data using the Universal Thermal Climate Index (UTCI) and physiological equivalent temperature (PET) to assess the effectiveness of a small water path and a cooling fog system. The results indicate that surface temperature reductions reached up to 1.1 °C, with the pergola area showing the most significant cooling effect, lowering PET values to an average of 36.2 °C. In contrast, the small water path recorded the highest PET values, peaking at nearly 50.2 °C, likely due to radiant heat from the surrounding surfaces. While these interventions provided localized cooling, their overall effect on urban temperature reduction remained modest. This study suggests that small-scale water features are effective in enhancing thermal comfort in neighborhood parks but must be integrated into broader urban cooling strategies to maximize their impact. [ABSTRACT FROM AUTHOR]

This study employs a sophisticated ecosystem modeling approach, specifically the European Regional Seas Ecosystem Model (ERSEM) coupled with the General Ocean Turbulence Model (GOTM), to conduct a comparative analysis of the pelagic ecosystem dynamics in the Yellow Sea and the waters surrounding Dokdo in the East Sea. Our research focuses on the complexities of carbon flux mechanisms within these ecosystems, emphasizing lower trophic levels and their roles in carbon export dynamics. Key findings reveal substantial differences in primary productivity, particulate organic carbon (POC) fluxes, and the timing of biological events between these two distinct marine environments. The Yellow Sea is characterized by significant stratification and lower light penetration, resulting in a condensed period of primary productivity, while the Dokdo waters benefit from clearer conditions that facilitate earlier and more sustained phytoplankton blooms. These disparities are critical for understanding the foundation of higher trophic levels and the efficiency of carbon export mechanisms. Our study underscores the profound impact of benthic-pelagic coupling, particularly in the Yellow Sea, highlighting the need for an integrated approach in marine ecosystem research. Through this comparative analysis, we advocate for enhanced monitoring and predictive modeling of shelf sea ecosystems to better understand their responses to environmental changes and to accurately forecast future dynamics. [ABSTRACT FROM AUTHOR]

Urban heat islands (UHI), which are exacerbated by climate change, significantly increase heat stress, particularly affecting vulnerable populations, such as the elderly and children. This study evaluates the effectiveness of various urban heat mitigation technologies, including cooling fog systems, cool roofs (reflective paint), shading structures, and small water paths, in reducing temperatures and enhancing thermal comfort. Field tests were conducted from 2021 to 2023 across Gimhae-si, Yechun-gun, Geyang-gu, and Sangju-si, with support from the Korean Ministry of Environment. The results demonstrated that cooling fog systems provided immediate temperature reductions, lowering ambient temperatures by up to 3.1 °C, while cool roofs reduced surface temperatures by 2–3 °C. Shading structures reduced surface temperatures by up to 10 °C, and small water paths cooled air temperatures by up to 1.5 °C, also increasing humidity and improving thermal comfort. The findings suggest that a combination of these technologies can effectively mitigate urban heat stress, especially in areas with vulnerable populations. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC) is a highly aggressive malignancy accounting for the majority of kidney cancers. Despite recent advancements in therapeutic options, the prognosis for advanced-stage RCC remains poor. Niemann–Pick C1-Like 1 (NPC1L1) plays a crucial role in cholesterol absorption and has been implicated in cancer progression across various cancers. However, its expression patterns and prognostic significance in RCC remain unclear. Methods: In this study, NPC1L1 expression in normal and RCC tissues, including subtypes, was compared using TCGA, GEPIA2, and The Human Protein Atlas. Clinical correlations were assessed, and the impact of NPC1L1 on overall survival (OS) and progression-free survival (PFS) was evaluated. Gene effect scores were analyzed using the DepMap tool to determine the involvement of NPC1L1 in RCC progression. Results: NPC1L1 expression was significantly lower in RCC tissues compared to normal tissues, particularly in the clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC) subtypes, but increased in advanced tumor stages. Higher NPC1L1 expression was associated with worse OS and PFS in RCC patients. Multivariable Cox regression confirmed NPC1L1 as an independent prognostic marker. Additionally, gene effect scores showed that NPC1L1 is essential for the survival of specific RCC cell lines. Conclusions: This study determines NPC1L1 as an independent prognostic indicator in RCC, with higher expression associated with poor survival outcomes. These findings suggest that NPC1L1 could serve as a valuable marker for identifying high-risk RCC patients. Further research is required to investigate the molecular mechanisms underlying the role of NPC1L1 in RCC progression. [ABSTRACT FROM AUTHOR]

We conducted a self-controlled case series study to investigate the association between COVID-19 vaccination and facial palsy (FP) in South Korea. We used a large immunization registry linked with the national health information database. We included 44,564,345 patients >18 years of age who received >1 dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad.26.COV2.S) and had an FP diagnosis and corticosteroid prescription within 240 days postvaccination. We compared FP incidence in a risk window (days 1-28) with a control window (the remainder of the 240-day observation period, excluding any risk windows). We found 5,211 patients experienced FP within the risk window and 10,531 experienced FP within the control window. FP risk increased within 28 days postvaccination, primarily after first and second doses and was observed for both mRNA and viral vaccines. Clinicians should carefully assess the FP risk-benefit profile associated with the COVID-19 vaccines and monitor neurologic signs after vaccination. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial dysfunction in the thyroid due to defective mitophagy has been observed in lymphocytic thyroiditis (LT). However, the effect of impaired mitophagy on the pathogenesis of LT is not well understood. The aim of this study is to investigate the role of mitophagy dysregulation in the thyroid gland. Methods: We analyzed RNA sequencing data of human thyroid glands with/without LT from Genotype-Tissue Expression (GTEx; n = 653) and performed RNA sequencing in thyroid glands of phosphatase and tensin homolog-induced putative protein kinase 1 (Pink1) knock-out and wild-type mice. We evaluated the phenotypic and histopathologic characteristics of the human (n = 16) and mouse thyroids. Additionally, we assessed cell proliferation, reactive oxygen species (ROS) production, and cytokine secretion of human thyroid epithelial cells (HTori-3) treated with PINK1 siRNA or a mitophagy inhibitor. Results: We found that expression of PINK1, a key regulator of mitophagy, was compromised in human thyroids with LT. Thyroid glands of Pink1-deficient mice exhibited increased inflammatory responses and nodular hyperplasia. Furthermore, mitophagy defects led to the production of pro-inflammatory cytokines and ROS in thyroid cells, resulting in immune cell recruitment. Notably, these mitophagy defects upregulated both the RNA expression and protein secretion of amphiregulin (AREG), an epidermal growth factor receptor (EGFR) ligand, in thyroid cells, while decreasing the protein expression of cAMP response element-binding protein (CREB), a transcription factor that suppresses AREG transcription. Finally, we demonstrated that aberrant cell proliferation in thyroid cells, driven by mitophagy defects, was mitigated after treatment with cetuximab, an EGFR inhibitor. Conclusions: In this study, we observed that mitophagy defects in the thyroid not only intensify inflammation through the accumulation of ROS, cytokine production, and immune cell recruitment but also contribute to hyperplasia via the EGFR pathway, facilitated by increased secretion of AREG from thyroid cells. [ABSTRACT FROM AUTHOR]

This paper proposes analytic forms of portfolio conditional value at risk (CoVaR) and the mean of the portfolio loss conditional on it being in financial distress (CoCVaR) on the normal tempered stable market model. Since CoCVaR captures the relative risk of the portfolio with respect to a benchmark return, we apply it to relative portfolio optimization. Moreover, we derive analytic forms for the marginal contribution to CoVaR and the marginal contribution to CoCVaR. We discuss the Monte-Carlo simulation method for calculating CoCVaR and the marginal contributions of CoVaR and CoCVaR. We provide an empirical illustration to show relative portfolio optimization with 30 stocks included in the Dow Jones Industrial Average under distressed conditions. Finally, we apply the risk budgeting method to reduce the CoVaR and CoCVaR of the portfolio based on the marginal contributions to CoVaR and CoCVaR. [ABSTRACT FROM AUTHOR]

Background and Objectives: Few comparative studies have evaluated wearable single-lead electrocardiogram (ECG) devices and standard multi-lead ECG devices during exercise testing. This study aimed to validate the accuracy of a wearable single-lead ECG monitor for recording heart rate (HR) metrics during graded exercise tests (GXTs). Methods: A cohort of 50 patients at a tertiary hospital underwent GXT while simultaneously being equipped with wearable single- and conventional multi-lead ECGs. The concordance between these modalities was quantified using the intraclass correlation coefficient and Bland–Altman plot analysis. Results: The minimum and average HR readings between the devices were generally consistent. Parameters such as ventricular ectopic beats and supraventricular ectopic beats showed strong agreement. However, the agreement for the Total QRS and Maximum RR was not sufficient. HR measurements across different stages of the exercise test showed sufficient agreement. Although not statistically significant, the standard multi-lead ECG devices exhibited higher noise levels compared to the wearable single-lead ECG devices. Conclusions: Wearable single-lead ECG devices can reliably monitor HR and detect abnormal beats across a spectrum of exercise intensities, offering a viable alternative to traditional multi-lead systems. [ABSTRACT FROM AUTHOR]

Rotavirus considerably threatens global health, particularly for children <5 years. Current, licensed oral attenuated vaccine formulations have limitations including insufficient efficacy in children in low- and middle-income countries, warranting urgent development of novel vaccines with improved efficacy and safety profiles. Herein, we present a novel approach utilizing an encapsulin (ENC) nanoparticle (NP)-based non-replicating rotavirus vaccine. ENC, originating from bacteria, offers a self-assembling scaffold that displays rotavirus VP8* antigens on its surface. To enhance the correct folding and soluble expression of monomeric antigens and their subsequent assembly into NP, we adopted an RNA-interacting domain (RID) of mammalian transfer RNA synthetase as an expression tag fused to the N-terminus of the ENC-VP8* fusion protein. Using the RID-ENC-VP8* tripartite modular design, insertion of linkers of appropriate length and sequence and the universal T cell epitope P2 remarkably improved the production yield and immunogenicity. Cleavage of the RID rendered a homogenous assembly of ENC-P2-VP8* into protein NPs. Immunization with ENC-P2-VP8* induced markedly higher levels of VP8*-specific antibodies and virus neutralization titers in mice than those induced by P2-VP8* without ENC. Altogether, these results highlight the potential of the designed ENC NP-based rotavirus vaccine as an effective strategy against rotavirus disease to address global health challenges. [ABSTRACT FROM AUTHOR]

There have been a growing number of corpus studies exploring the role of linguistic experience or input in sentence processing. Previous studies have used frequencies in first language (L1) corpora to represent the input of second language (L2) learners, but it has been claimed that L2 output as well as L1 output contribute to L2 acquisition and processing (Ellis 2002; Ellis and Collins 2009; Ellis and Wulff 2020). By analyzing an L2 corpus produced by Korean adult learners of English, this paper aims to establish more accurate input for L2 learners and investigate why Korean adult learners of English are sensitive to noun animacy and topicality in processing English relative clauses, as native speakers of English are. The results of the L2 corpus analysis reveal that object and subject relative clauses display different distributional patterns with respect to head noun animacy, embedded noun animacy, and the topicality of the embedded NP due to their strong tendency to have unmarked subjects and objects in terms of animacy and topicality. This paper proposes that the experience of subjecthood and objecthood, which are crosslinguistically associated with noun animacy and topicality, plays a role in producing and processing relative clauses in L2 which is syntactically different from the native language of L2 speakers. In addition, I discuss that some processing differences between L1 and L2 can arise due to L2 learners’ experience with their native language. [ABSTRACT FROM AUTHOR]

Various data types generated in the semiconductor manufacturing process can be used to increase product yield and reduce manufacturing costs. On the other hand, the data generated during the process are collected from various sensors, resulting in diverse units and an imbalanced dataset with a bias towards the majority class. This study evaluated analysis and preprocessing methods for predicting good and defective products using machine learning to increase yield and reduce costs in semiconductor manufacturing processes. The SECOM dataset is used to achieve this, and preprocessing steps are performed, such as missing value handling, dimensionality reduction, resampling to address class imbalances, and scaling. Finally, six machine learning models were evaluated and compared using the geometric mean (GM) and other metrics to assess the combinations of preprocessing methods on imbalanced data. Unlike previous studies, this research proposes methods to reduce the number of features used in machine learning to shorten the training and prediction times. Furthermore, this study prevents data leakage during preprocessing by separating the training and test datasets before analysis and preprocessing. The results showed that applying oversampling methods, excluding KM SMOTE, achieves a more balanced class classification. The combination of SVM, ADASYN, and MaxAbs scaling showed the best performance with an accuracy and GM of 85.14% and 72.95%, respectively, outperforming all other combinations. [ABSTRACT FROM AUTHOR]

Semiconductor nanocrystals with an anisotropic morphology exhibit unique properties, most notably their linear polarization. The colloidal growth of semiconductor nanorods with core dots inside, also referred to as dot-in-rod (DIR) structure, has enabled the synthesis of anisotropic nanocrystals with better stability and controllable fluorescence polarization. In this study, we synthesize CdSe/CdS DIR nanocrystals, in which the position of the CdSe core particle can be controlled by using different ligand compositions during the CdS growth. Varying the core position within the DIR structure, e.g., from the center to the end of the DIR particles, results in a change in the degree of linear polarization. When the core is positioned at the center of the nanorod, the linear polarization turns out to be higher compared with tip-core DIRs. Time-resolved photoluminescence analysis reveals that the center-core DIRs have higher electron–hole interaction than tip-core DIRs because of weak uniaxial strain in center-core DIR that arises from lattice dislocations at the interface to relieve accumulated strain. [ABSTRACT FROM AUTHOR]

We present the Group Cohesion and Emotion (GCE) dataset, which comprises 1029 segmented films sourced from YouTube. These videos encompass a range of interactions, including interviews, meetings, informal discussions, and other similar contexts. In the annotation process, graduate psychology students were tasked with assigning coherence levels, ranging from 1 to 7, and affective states as negative, neutral, or positive for each 30 s film. We introduce a foundational model that utilizes advanced visual and audio embedding techniques to investigate the concepts of group cohesion and group emotion prediction. The application of Multi-Head Attention (MHA) fusion is utilized to enhance the process of cross-representation learning. The scope of our investigation includes both unimodal and multimodal techniques, which provide insights into the prediction of group cohesion and the detection of group emotion. The results emphasize the effectiveness of the GCE dataset in examining the level of group unity and emotional conditions. [ABSTRACT FROM AUTHOR]

Structural deformation modifies the bandgap, exciton fine structure and phonon energy of semiconductors, providing an additional knob to control their optical properties. The impact can be exploited in colloidal semiconductor quantum dots (QDs), wherein structural stresses can be imposed in three dimensions while defect formation is suppressed by controlling surface growth kinetics. Yet, the control over the structural deformation of QDs free from optically active defects has not been reached. Here, we demonstrate strain-graded CdSe-ZnSe core-shell QDs with compositionally abrupt interface by the coherent pseudomorphic heteroepitaxy. Resulting QDs tolerate mutual elastic deformation of varying magnitudes at the interface with high structural fidelity, allowing for spectrally stable and pure emission of photons at accelerated rates with near unity luminescence efficiency. We capitalize on the asymmetric strain effect together with the quantum confinement effect to expand emission envelope of QDs spanning the entire visible region and exemplify their use in photonic applications. Structural deformation can modify the optical properties of quantum dots. Here, the author report strain-graded CdSe-ZnSe quantum dots, allowing for spectrally stable and pure emission of photons at accelerated rates with near unity luminescence efficiency. [ABSTRACT FROM AUTHOR]

Purpose: Rare diseases necessitate consistent access to specialized health services. In Korea, despite the growing socioeconomic burden, insufficient comprehensive research is available on patients with rare diseases and their families, particularly concerning factors influencing the length of time to diagnosis. The aim of this study was to thoroughly characterize rare pediatric diseases and explore factors impacting the diagnostic odyssey. Methods: The study enrolled patients under 15 years old seeking medical care at the Seoul National University Children’s Hospital Rare Disease Center between January 2022 and December 2023. Participating patients were required to have been diagnosed with one of the 1,248 rare diseases recognized in Korea. A 33-question survey was developed to assess clinical features of the patients, characteristics of their primary caregivers, and their perceptions of ongoing medical care. Results: The study included 101 patients and their families. Regarding perceived cognitive and motor functions, most families indicated moderate or severe limitations (cognitive, 62.4%; motor, 57.4%). Over half of the families (53.5%) reported discontinuing employment to provide patient care. Neurological symptoms represented the most common initial chief concern, with dermatologic symptoms and laboratory test abnormalities also noted. Three factors were associated with time to diagnosis: the number of hospitals visited, whether the districts of residence and diagnosis aligned, and the age at symptom onset. Conclusion: The comprehensive characterization of patients with rare diseases and their families in Korea, along with the identification of factors impacting the diagnostic odyssey, provides key insights for the development of a tailored support system. [ABSTRACT FROM AUTHOR]

Solid–water interfaces are crucial for clean water, conventional and renewable energy, and effective nuclear waste management. However, reflecting the complexity of reactive interfaces in continuum-scale models is a challenge, leading to oversimplified representations that often fail to predict real-world behavior. This is because these models use fixed parameters derived by averaging across a wide physicochemical range observed at the molecular scale. Recent studies have revealed the stochastic nature of molecular-level surface sites that define a variety of reaction mechanisms, rates, and products even across a single surface. To bridge the molecular knowledge and predictive continuum-scale models, we propose to represent surface properties with probability distributions rather than with discrete constant values derived by averaging across a heterogeneous surface. This conceptual shift in continuum-scale modeling requires exponentially rising computational power. By incorporating our molecular-scale understanding of solid–water interfaces into continuum-scale models we can pave the way for next generation critical technologies and novel environmental solutions. Chemistry at solid-water interfaces is crucial for all aspects of human life. Here, authors propose to use a probability-based paradigm for formalizing chemical reactions at solid-water interfaces in continuum scale models. [ABSTRACT FROM AUTHOR]

Solid–water interfaces are crucial for clean water, conventional and renewable energy, and effective nuclear waste management. However, reflecting the complexity of reactive interfaces in continuum-scale models is a challenge, leading to oversimplified representations that often fail to predict real-world behavior. This is because these models use fixed parameters derived by averaging across a wide physicochemical range observed at the molecular scale. Recent studies have revealed the stochastic nature of molecular-level surface sites that define a variety of reaction mechanisms, rates, and products even across a single surface. To bridge the molecular knowledge and predictive continuum-scale models, we propose to represent surface properties with probability distributions rather than with discrete constant values derived by averaging across a heterogeneous surface. This conceptual shift in continuum-scale modeling requires exponentially rising computational power. By incorporating our molecular-scale understanding of solid–water interfaces into continuum-scale models we can pave the way for next generation critical technologies and novel environmental solutions. Chemistry at solid-water interfaces is crucial for all aspects of human life. Here, authors propose to use a probability-based paradigm for formalizing chemical reactions at solid-water interfaces in continuum scale models. [ABSTRACT FROM AUTHOR]

Background: We investigated the association between exercise habits before or after thyroidectomy and incident type 2 diabetes mellitus (T2DM) in patients with thyroid cancer. Methods: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy for the treatment of thyroid cancer between 2010 and 2016 was performed using the Korean National Health Information Database. Regular exercise was defined as mid-term or vigorous exercise at least 1 day in a week based on a self-reported questionnaire. Patients were divided into four groups according to exercise habits before and after thyroidectomy: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. Results: During a median follow-up of 4.5 years, 2,720 (3.91%) patients developed T2DM. The incidence of T2DM per 1,000 person years was lower in patients who performed regular exercise before or after thyroidectomy than in persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the new exerciser group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78–0.97), the exercise dropout group (HR 0.81, 95% CI 0.72–0.91), and the exercise maintainer group (HR 0.84, 95% CI 0.76–0.93) had lower risks of incident T2DM. Exercising < 1,500 MET-minutes/week in the exercise maintainer group was associated with a lower risk of incident T2DM compared with persistent non-exercisers (< 500: HR 0.80, 95% CI 0.67–0.96, P = 0.002; 500 to < 1,000: HR 0.81, 95% CI 0.71–0.93, P < 0.001; 1,000 to < 1,500: HR 0.81, 95% CI 0.69–0.94, P < 0.001). Conclusions: Regular exercise before or after thyroidectomy was associated with a lower risk of incident T2DM in patients with thyroid cancer. [ABSTRACT FROM AUTHOR]

Trash or garbage is one of the most dangerous health and environmental problems that affect pollution. Pollution affects nature, human life, and wildlife. In this paper, we propose modern solutions for cleaning the environment of trash pollution by enforcing strict action against people who dump trash inappropriately on streets, outside the home, and in unnecessary places. Artificial Intelligence (AI), especially Deep Learning (DL), has been used to automate and solve issues in the world. We availed this as an excellent opportunity to develop a system that identifies trash using a deep convolutional neural network (CNN). This paper proposes a real-time garbage identification system based on a deep CNN architecture with eight distinct classes for the training dataset. After identifying the garbage, the CCTV camera captures a video of the individual placing the trash in the incorrect location and sends an alert notice to the relevant authority. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical impact of suspicious extra-abdominal lymph nodes (EALNs) identified preoperatively on CT and/or PET/CT images in advanced ovarian cancer. Methods: A retrospective study was conducted with 122 patients diagnosed with stage III or IV ovarian cancer with preoperative CT and/or PET/CT images from 2006 to 2022. Imaging studies were evaluated for the presence, size and location of suspicious EALNs. Suspicious lymph node enlargement was defined by a cut-off ≥5mm short-axis dimension on CT and/or lesions with maximum standardized uptake values of ≥2.5 on PET/CT. This study only included patients who did not have their EALNs surgically removed. Results: A total 109 patients met the inclusion criteria; 36 (33%) had suspicious EALNs and were categorized as "node-positive". The median overall survival (OS) was 45.73 months for the "node-positive" and 46.50 months for the "node-negative" patients (HR 1.17, 95% CI 0.68–2.00, p = 0.579). In multivariate analysis, after adjusting for other variables selected by process of backward elimination using a significance level of p<0.20, suspicious EALNs still showed no clinical significance on OS (aHR 1.20, 95% CI 0.67–2.13, p = 0.537) as well as progression-free survival (aHR 1.43, 95% CI 0.85–2.41, p = 0.174). Old age (aHR 2.23, 95% CI 1.28–3.89, p = 0.005) and platinum resistance (aHR 1.92, 95% CI 1.10–3.36, p = 0.023) affects adversely on OS. Conclusion: Suspicious EALNs did not worsen the prognosis of patients with advanced ovarian cancer. However, its impact on survival is not yet clarified. Further investigation is required to assess the clinical significance of suspicious EALNs on preoperative imaging studies. [ABSTRACT FROM AUTHOR]

B cell receptors (BCRs) denote antigen specificity, while corresponding cell subsets indicate B cell functionality. Since each B cell uniquely encodes this combination, physical isolation and subsequent processing of individual B cells become indispensable to identify both attributes. However, this approach accompanies high costs and inevitable information loss, hindering high-throughput investigation of B cell populations. Here, we present BCR-SORT, a deep learning model that predicts cell subsets from their corresponding BCR sequences by leveraging B cell activation and maturation signatures encoded within BCR sequences. Subsequently, BCR-SORT is demonstrated to improve reconstruction of BCR phylogenetic trees, and reproduce results consistent with those verified using physical isolation-based methods or prior knowledge. Notably, when applied to BCR sequences from COVID-19 vaccine recipients, it revealed inter-individual heterogeneity of evolutionary trajectories towards Omicron-binding memory B cells. Overall, BCR-SORT offers great potential to improve our understanding of B cell responses. [ABSTRACT FROM AUTHOR]

Background: Myelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases. Methods: The sera of patients with MOGAD (from during an attack and remission; N=19 and N=9, respectively) and AQP4-NMOSD (N=35 and N=17), and healthy controls (N=38) were analyzed for C1q-binding circulating immune complex (CIC-C1q), C1 inhibitor (C1-INH), factor H (FH), C3, iC3b, and soluble terminal complement complex (sC5b-9). Results: In attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all, p<0.001), while the level of sC5b-9 was increased only in the NMOSD group. In MOGAD, there were no differences in the concentrations of complement analytes based on disease status. However, within AQP4-NMOSD, remission samples indicated a higher C1-INH level than attack samples (p=0.003). Notably, AQP4-NMOSD patients on medications during attack showed lower levels of iC3b (p<0.001) and higher levels of C3 (p=0.008), C1-INH (p=0.004), and sC5b-9 (p<0.001) compared to those not on medication. Among patients not on medication at the time of attack sampling, serum MOG-IgG cell-based assay (CBA) score had a positive correlation with iC3b and C1-INH levels (rho=0.764 and p=0.010, and rho=0.629 and p=0.049, respectively), and AQP4-IgG CBA score had a positive correlation with C1-INH level (rho=0.836, p=0.003). Conclusions: This study indicates a higher prominence of complement pathway activation and subsequent C3 degradation in MOGAD compared to AQP4-NMOSD. On the other hand, the production of terminal complement complexes (TCC) was found to be more substantial in AQP4-NMOSD than in MOGAD. These findings suggest a strong regulation of the complement system, implying its potential involvement in the pathogenesis of MOGAD through mechanisms that extend beyond TCC formation. [ABSTRACT FROM AUTHOR]

The COVID-19 Vaccine Safety Research Committee (CoVaSC) was established in November 2021 to address the growing need for independent, in-depth scientific evidence on adverse events (AEs) following coronavirus disease 2019 (COVID-19) vaccination. This initiative was requested by the Korea Disease Control and Prevention Agency and led by the National Academy of Medicine of Korea. In September 2022, the COVID-19 Vaccine Safety Research Center was established, strengthening CoVaSC's initiatives. The center has conducted various studies on the safety of COVID-19 vaccines. During CoVaSC's second research year, from September 29, 2022 to July 19, 2023, the center was restructured into 4 departments: Epidemiological Research, Clinical Research, Communication & Education, and International Cooperation & Policy Research. Its main activities include (1) managing CoVaSC and the COVID-19 Vaccine Safety Research Center, (2) surveying domestic and international trends in AE causality investigation, (3) assessing AEs following COVID-19 vaccination, (4) fostering international collaboration and policy research, and (5) organizing regular fora and training sessions for the public and clinicians. Causality assessments have been conducted for 27 diseases, and independent research has been conducted after organizing ad hoc committees comprising both epidemiologists and clinical experts on each AE of interest. The research process included protocol development, data analysis, interpretation of results, and causality assessment. These research outcomes have been shared transparently with the public and healthcare experts through various fora. The COVID-19 Vaccine Safety Research Center plans to continue strengthening and expanding its research activities to provide reliable, high-quality safety information to the public. [ABSTRACT FROM AUTHOR]

Purpose: To explore factors influencing compliance with COVID-19 recommended preventive behaviours focusing on types of information sources about COVID-19, learning about disinfectant use and constructs of the Health Belief Model among adolescents at the start of the COVID-19 pandemic. Design: Cross-sectional descriptive design. Setting: A survey was distributed electronically to organisations, parents and student groups in Southern California 10 months after the declaration of the COVID-19 pandemic. Sample: A total of 217 students aged between 12 and 19 years old. Measures: Questions were adapted from a previous nationwide online survey about COVID-19. Analysis: Descriptive and logistic regression analyses were used to analyse the data. Results: The most common type of information (communication) source was an interpersonal one (parents), and the least common type was an official (federal, school) source. Statistically significant better protective behaviours aligned with COVID-19 recommendations were seen in students who received more information from official sources; less information from social media or friends; believed in the accuracy and benefits of utilising the COVID-19 pandemic information and learned about the use of disinfectants and were confident in cleaning surfaces of devices and equipped. However, those who perceived themselves at risk of COVID-19 infection and had perceived high risks in general reported lower (but not statistically significant) compliance with protective behaviour. The level of knowledge about COVID-19 was not statistically associated with compliance with protective behaviour. Conclusion: Parents' role in guiding adolescents is critical. Evidence-based information about COVID-19 should be delivered through official sources to facilitate adolescents' understanding and active participation in public health efforts. [ABSTRACT FROM AUTHOR]

The carbon monoxide (CO) in the marine boundary layer and in the surface waters and water column were measured along the western limb of the North Pacific from the Korean Peninsula to Alaska, USA, in summer 2012. The observation allows us to estimate the CO budgets in the surface mixed layer of the three distinct regimes: the East Sea (Sea of Japan) (ES), the Northwest Pacific (NP), and the Bering Sea (BS). CO photochemical production rates were 56(± 15) µ mol m -2 d -1 , 27(± 3) µ mol m -2 d -1 , and 26(± 2) µ mol m -2 d -1 , while microbial consumption rates were 30(± 8) µ mol m -2 d -1 , 24(± 5) µ mol m -2 d -1 , and 63(± 19) µ mol m -2 d -1 in the ES, NP, and BS, respectively, both of which are the dominant components of the CO budget in the ocean. The other two known components, air–sea gas exchange and downward mixing, remained negligible (less than 3 µ mol m -2 d -1) in all regimes. While the CO budget in the surface mixed layer of the NP was in balance, the CO production surpassed the consumption in the ES, and vice versa in the BS. The significant imbalances in the CO budget in the ES (25 ± 17 µ mol m -2 d -1) and the BS (40 ± 19 µ mol m -2 d -1) are suggested to be compensated by external physical transport such as lateral advection, subduction, or ventilation. Notably, the increase in the CO column burden correlated with the imbalance in the CO budget, highlighting the significant role of the physical transport in the marine CO cycles. Our observation, for the first time, underscores the potential importance of physical transport in driving CO dynamics in the marine environment. [ABSTRACT FROM AUTHOR]

Background: The predictive factors for lateral neck lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) remain undetermined. This study investigated the clinicopathological characteristics, transcriptomes, and tumor microenvironment in PTMC according to the LLNM status. We aimed to identify the biomarkers associated with LLNM development. Methods: We retrospectively reviewed the medical records of patients with PTMC from two independent institutions between 2018 and 2022 (n=597 and n=467). We compared clinicopathological features between patients without lymph node metastasis (N0) and those with LLNM (N1b). Additionally, laser capture microdissection and RNA sequencing were performed on primary tumors from both groups, including metastatic lymph nodes from the N1b group (n=30; 20 primary tumors and 10 paired LLNMs). We corroborated the findings using RNA sequencing data from 16 BRAF-like PTMCs from The Cancer Genome Atlas. Transcriptomic analyses were validated by immunohistochemical staining. Results: Clinicopathological characteristics, such as male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis showed associations with LLNM in PTMCs. Transcriptomic profiles between the N0 and N1b PTMC groups were similar. However, tumor microenvironment deconvolution from RNA sequencing and immunohistochemistry revealed an increased abundance of tumor-associated macrophages, particularly M2 macrophages, in the N1b group. Conclusion: Patients with PTMC who have a male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis exhibited an elevated risk for LLNM. Furthermore, infiltration of M2 macrophages in the tumor microenvironment potentially supports tumor progression and LLNM in PTMCs. [ABSTRACT FROM AUTHOR]

Background: Current research has not investigated the effect of thyroid-stimulating hormone suppression therapy with levothyroxine on the risk for developing subsequent primary cancers (SPCs). This study aimed to investigate the association between levothyroxine dosage and the risk for SPCs in thyroid cancer patients. Methods: We conducted a nationwide population-based retrospective cohort study form Korean National Health Insurance database. This cohort included 342,920 thyroid cancer patients between 2004 and 2018. Patients were divided into the non-levothyroxine and the levothyroxine groups, the latter consisting of four dosage subgroups according to quartiles. Cox proportional hazard models were performed to evaluate the risk for SPCs by adjusting for variables including cumulative doses of radioactive iodine (RAI) therapy. Results: A total of 17,410 SPC cases were observed over a median 7.3 years of follow-up. The high-dose levothyroxine subgroups (Q3 and Q4) had a higher risk for SPC (adjusted hazard ratio [HR], 1.14 and 1.27; 95% confidence interval [CI], 1.05-1.24 and 1.17-1.37; respectively) compared to the non-levothyroxine group. In particular, the adjusted HR of stomach (1.31), colorectal (1.60), liver and biliary tract (1.95), and pancreatic (2.48) cancers were increased in the Q4 subgroup. We consistently observed a positive association between high levothyroxine dosage per body weight and risk of SPCs, even after adjusting for various confounding variables. Moreover, similar results were identified in the stratified analyses according to thyroidectomy type and RAI therapy, as well as in a subgroup analysis of patients with good adherence. Conclusion: High-dose levothyroxine use was associated with increased risk of SPCs among thyroid cancer patients regardless of RAI therapy. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effect of adding flame‐retardant melamine and five different dispersants on the precipitation, foaming, mechanical, and thermal properties of flexible polyurethane foam (FPUF). Precipitation experiments were conducted to analyze the effect of dispersant on the separation of flame retardant and polyol, and the foaming characteristics of polyurethane (PU) foam after adding dispersant were analyzed. The effect of adding a dispersant on mechanical strength was characterized by measuring tensile strength, tearing strength, and hardness, and scanning electron microscopy analysis was performed to analyze morphological characteristics. Thermogravimetric analysis (TGA) was performed to analyze the thermal properties of PU foam. A horizontal flame test, limiting oxygen index test, and cone calorimeter tests were conducted to examine the flame retardancy of PU foam with flame retardant melamine and dispersant added. The dispersant ANTI‐TERRA‐U is a solution of a salt of unsaturated polyamine amides and low‐molecular acidic polyesters. And, the dispersant BYK‐220S is a solution of a low molecular weight, unsaturated acidic polycarboxylic acid polyester with a polysiloxane copolymer. The dispersants ANTI‐TERRA‐U and BYK‐220S improved the density, tensile strength, tear strength, and hardness of FPUF. TGA of the top and bottom portions of the foam showed less weight difference for samples containing dispersants, indicating better homogeneity due to improved dispersibility. Therefore, we conclude that dispersants are beneficial additives to improve the mechanical properties and dispersibility of PU foam. [ABSTRACT FROM AUTHOR]

Eukaryotic cells exhibit random migration in the absence of extracellular directional cues. This random migration acts as basal motility for various migratory responses such as chemotaxis. The self-organization of random motility requires the internal signals that determine the anterior side of the migrating cell be generated spontaneously from the intrinsic activities of intracellular signaling networks. Recent studies have identified an excitable system as the mechanism of the spontaneous signal generation. Here, we discuss how the excitable system of Ras, a small G protein, regulates signaling networks in Dictyostelium discoideum as a model organism. The excitability produces a domain where an active form of Ras is enriched on the cell membrane without extracellular directional cues, such that Ras serves as the anterior signal. The typical spatiotemporal characteristics are mathematically explained by reaction-diffusion models. These models further enable a quantitative analysis of the dynamics that depends on the internal cellular states and surrounding environments. Downstream of the Ras excitable system, a phosphoinositide metabolic network composed of PI3K, PTEN, PI(3,4,5)P3 and PI(4,5)P2 exhibits bistability to discretize the anterior and posterior regions of the cell membrane. Upstream, a local excitation and global inhibition local excitation global inhibition network, which works for gradient sensing in the presence of chemoattractant gradients, spatiotemporally biases the excitability of Ras for chemotaxis. In parallel with the Ras excitable system, the cGMP signaling pathway constitutes another excitable system of its own periodicity to ensure flexible migratory dynamics. In addition to these intracellular signaling networks, an intercellular signaling network activated by secreted cAMP is coupled with the Ras excitable system for collective cell migration. Finally, we discuss how the excitable system of Ras operates as a platform of information integration by receiving multiple intrinsic and extrinsic signals to ensure spontaneous cellular activity and robust responses in eukaryotic cell migration under natural complex environments. [ABSTRACT FROM AUTHOR]

We investigated seasonal net community production (NCP) variations in the productive Amundsen Sea Polynya, integrating observational data and ecosystem modeling. NCP estimates (NCPO2/Ar) from in situ O2/Ar data during the austral summer (January‐March) from 2011 to 2018 were compared with those from a one‐dimensional ecosystem model. Early January saw the highest NCPO2/Ar values ranging from 115 to 139 mmol O2 m−2 d−1 among observations. Over the summer, NCPO2/Ar gradually decreased, reaching 40 mmol O2 m−2 d−1 by late February. Late summer values, though one‐third of early January, remained notably positive, indicating net autotrophy. This persisted despite sea surface temperature dropping from >−0.4°C in January to −1.33°C in late February. Refining NCPO2/Ar, we modified bacterial dynamics in our ecosystem model. Significantly improved model performance resulted from two key modifications. First, we introduced bacterial uptake dependency on Phaeocystis primary production. Second, we heightened temperature‐dependent bacterial respiration and production approximately fifteenfold. These changes revealed NCP's remarkable sensitivity to minor temperature fluctuations (<1°C). Furthermore, modified bacterial dynamics delayed the net primary production peak by 2 weeks, underlining the importance of phytoplankton‐bacteria interaction in the ocean carbon cycle. Model results estimated annual NCP in the Amundsen Sea Polynya at 4.04 mol C m−2, aligning with summer NCP estimates (0.2–5.9 mol C m−2) in observational study. Our study advances NCP understanding in polar regions, emphasizing comprehensive observations, including bacterial processes, for understanding intricate biotic interactions. These findings align with past observations on bacterial metabolism and Phaeocystis ecological properties in the Antarctic oceans. Plain Language Summary: Our study delved into the seasonal changes in productivity in the Amundsen Sea Polynya, a bustling region near Antarctica. We combined real‐world observations with computer modeling to unravel these patterns. In early January, this area was super productive, generating lots of oxygen. As summer progressed, productivity slowly declined, but it remained positive even in late summer, despite a significant drop in ocean temperature. This suggested that the ecosystem continued to thrive. To refine our model, we adjusted how bacteria interacted in the ecosystem. The results were fascinating. When we made bacteria more reliant on a specific algae, Phaeocystis, and more sensitive to temperature, our model better matched real‐world conditions. This revealed that even minor water temperature changes, less than 1°C, could significantly impact this ecosystem. Furthermore, altering bacterial dynamics led to a 2‐week delay in the peak period of ocean plant growth, highlighting the crucial role of the interaction between tiny plants called phytoplankton and bacteria in the ocean's carbon cycle. Our study provides valuable insights into polar regions, emphasizing the need for comprehensive observations that include bacterial activities. Understanding these intricate interactions is vital for grasping the bigger picture of life in these remote and extreme environments. Key Points: Net community production in the Amundsen Sea Polynya was investigated by integrating observational data with ecosystem modelingPhaeocystis‐driven nutrient remineralization by bacteria stimulates phytoplankton growthBacterial respiration peaks within specific temperature range, affecting carbon cycling in Antarctic polynyas [ABSTRACT FROM AUTHOR]

The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression. [ABSTRACT FROM AUTHOR]

Introduction: A reliable standard model is required to evaluate the efficacy of new drugs for companion animals, especially dogs. Canine atopic dermatitis (cAD), also known as allergic inflammatory skin disease, is a common condition. Currently, the house dust mite animal model is used in the research of cAD; however, this model exhibits significant individual variation and is difficult to standardize. In this study, we used ovalbumin as an antigen to sensitize and stimulate dogs, thereby establishing a stable model mimicking the T-helper 2 (Th2) response seen in cAD. Our objective was to create a cAD model that could be employed to evaluate the efficacy of novel drugs and mimic the Th2 dominant allergic response observed in the pathogenesis of atopic dermatitis of dogs. Methods: In this study, six beagles were used. Normal saline was applied to two animals, and ovalbumin to four, on their dorsal skin. Results: The ovalbumin-treated groups exhibited clinical cAD symptoms, such as pruritus and erythema. Moreover, plasma levels of the cAD markers immunoglobulin E and CCL17 chemokine were higher in the ovalbumin-treated group than in the vehicle control group. The skin thickness of the epidermis was significantly increased in the ovalbumin-treated group, with infiltration of inflammatory cells observed in the thickened dermis region. In conclusion, treatment of canine skin with an optimal concentration of ovalbumin induced typical cAD-like symptoms, and histological and molecular analyses confirmed an enhanced Th2-related immune response. Conclusion: Therefore, we successfully established a suitable Th2-dominant response mimicking cAD, which will facilitate targeted research of atopic dermatitis in dogs. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Patients with kidney disease have been prioritized for coronavirus disease 2019 (COVID-19) vaccination due to their susceptibility to COVID-19 infection. However, little evidence exists regarding these patients' vulnerability to COVID-19 post-vaccination. Thus, we evaluated the risk of COVID-19 in patients with kidney disease compared to individuals without kidney disease according to vaccination status. METHODS: A retrospective cohort study was conducted using the Korean nationwide COVID-19 registry linked with National Health Insurance Service claims data (2018-2021). Among individuals aged 12 years or older, 2 separate cohorts were constructed: a COVID-19-vaccinated cohort and an unvaccinated cohort. Within each cohort, the risk of COVID-19 infection and all-cause mortality, hospitalization, and emergency room visits within 30 days of COVID-19 infection were compared between patients with and without kidney disease. To adjust for potential confounding, we used propensity score matching. Hazard ratios (HRs) for each outcome were estimated using a Cox proportional hazard model. RESULTS: We identified 785,390 and 836,490 individuals in the vaccinated and unvaccinated cohorts, respectively. Compared to patients without kidney disease, patients with kidney disease were at a higher risk of COVID-19 infection in both the vaccinated cohort (HR, 1.08; 95% confidence interval [CI], 1.02 to 1.16) and the unvaccinated cohort (HR, 1.09; 95% CI, 0.99 to 1.20). Likewise, patients with kidney disease generally were at higher risk for severe clinical outcomes within 30 days of COVID-19 infection. Subgroup and sensitivity analyses showed generally consistent results. CONCLUSIONS: Our study observed excess risk of COVID-19 in patients with kidney disease, highlighting the importance of ongoing attention to these patients even post-vaccination. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The purpose of this study was to assess the effectiveness of human papillomavirus (HPV) vaccination administered to adolescent girls through Korea's National Immunization Program. METHODS: This retrospective cohort study included patients who were 12-13 years old, whether vaccinated or unvaccinated, between July 2016 and December 2017. The incidence of genital warts (GWs) was monitored through 2021. Time-stratified hazard ratios (HRs) were estimated, adjusting for birth year, socioeconomic status, and the level of urbanization of the region, and were presented with 95% confidence intervals (CIs). Data were sourced from the Immunization Registry Integration System, linked with the National Health Information Database. RESULTS: The study included 332,062 adolescent girls, with an average follow-up period of approximately 4.6 years. Except for the first year, the HRs for the vaccinated group were lower than those for the unvaccinated group. The HRs for specific cut-off years were as follows: year 2, 0.62 (95% CI, 0.31 to 1.13); year 3, 0.58 (95% CI, 0.35 to 0.96); and year 4 and beyond, 0.39 (95% CI, 0.28 to 0.52). CONCLUSIONS: Our findings indicate that HPV vaccination was associated with a reduction in the risk of GWs among adolescent girls. Notably, this reduction became significant as the incidence of GWs increased with age. [ABSTRACT FROM AUTHOR]

Introduction: Atezolizumab and bevacizumab (Ate/Bev) combination has become the new first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). Although several studies reported thyroid dysfunction after treatment with immune checkpoint inhibitors, the clinical and immunological significance of thyroid dysfunction in patients treated with Ate/Bev has not been comprehensively addressed. We aimed to comprehensively evaluate the clinical and immunological implications of thyroid dysfunction in unresectable HCC patients treated with Ate/Bev. Methods: We enrolled 208 patients with unresectable HCC treated with Ate/Bev from three Korean cancer centers. Thyroid adverse events (AEs) were reviewed, and cytokines and T cells in the blood samples were analyzed at baseline. For external validation, we analyzed clinical outcomes according to thyroid AEs in patients treated with Ate/Bev in the IMbrave150 study. Results: Forty-one (19.7%) out of 208 patients experienced thyroid dysfunction (hypothyroidism [17.3%] and thyrotoxicosis [5.8%]) after Ate/Bev treatment. Median time to onset of hypothyroidism and thyrotoxicosis after Ate/Bev treatment was 3.5 and 1.3 months, respectively. Patients with thyroid AEs demonstrated significantly better progression-free survival, overall survival, and objective response rate than those without thyroid AEs. These findings were still consistent even after adjusting for confounding factors. Furthermore, favorable survival outcomes in patients with thyroid AEs were also validated in a cohort of IMbrave150 patients. While patients with thyrotoxicosis showed a significantly lower level of baseline IL-6, those with hypothyroidism did not show significant differences in circulating cytokine levels and CD8+ T-cell fractions. Conclusions: A fraction of patients with HCC treated with Ate/Bev experienced thyroid dysfunction, and the development of thyroid AEs was associated with favorable clinical outcomes. [ABSTRACT FROM AUTHOR]