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This design-based study explored the digital and linguistic practices of South Korean adolescents from a rural area within the Write4Change global online community, emphasizing their use of image-driven tools. Framed within the cosmopolitan literacies perspective, these adolescents adeptly merge local and global dimensions, integrating their multilingual identities, and compelling visual narratives into their work. They navigate English, the dominant language of the online community, while incorporating multilingual elements to enrich community dialogues. These practices reflect their linguistic adaptability and digital literacies and underscore the significant role of cosmopolitan literacies in transforming literacy studies. The study highlights the impactful digital practices of South Korean adolescents, contributing to a broader understanding of inclusivity and diversity in global literacies.

Abstract In esophageal adenocarcinoma, the presence of lymph node metastases predicts patients' survival even after curative resection. Currently, there is no highly accurate marker for detecting the presence of lymph node metastasis. The SEMA3F/NRP2 axis was initially characterized in axon guidance and recent evidence has revealed its significant involvement in lymphangiogenesis, angiogenesis, and carcinogenesis. Hence, the objective of this study was to elucidate the roles of SEMA3F and its receptor NRP2 in esophageal adenocarcinoma. We conducted an immunohistochemical evaluation of SEMA3F and NRP2 protein expression in 776 patients with esophageal adenocarcinoma who underwent Ivor-Lewis esophagectomy at the University Hospital of Cologne. Total and positive cancer cell counts were digitally analyzed using QuPath and verified by experienced pathologists to ensure accuracy. Positive expression was determined as a cell percentage exceeding the 50th percentile threshold. In our cohort, patients exhibiting SEMA3F positive expression experience significantly lower pT- and pN-stages. In contrast, positive NRP2 expression is associated with the presence of lymph node metastases. Survival analyses showed that the expression status of NRP2 had no impact on patient survival. However, SEMA3F positivity was associated with a favorable patient survival outcome (median OS: 38.9 vs. 26.5 months). Furthermore, SEMA3F could be confirmed as an independent factor for better patient survival in patients with early tumor stage (pT1N0-3: HR = 0.505, p = 0.014, pT1-4N0: HR = 0.664, p = 0.024, pT1N0: HR = 0.483, p = 0.040). In summary, SEMA3F emerges as an independent predictor for a favorable prognosis in patients with early-stage esophageal adenocarcinoma. Additionally, NRP2 expression is linked to a higher risk of lymph node metastases occurrence. We hypothesize that low SEMA3F expression could identify patients with early-stage tumors who might benefit from more aggressive treatment options or intensified follow-up. Furthermore, SEMA3F and its associated pathways should be explored as potential tumor-suppressing agents.

Abstract Background To examine the association between glycemic status and all-cause mortality risk among individuals with dementia. Methods We enrolled 146,832 individuals aged 40 and older with dementia as identified through the Korean National Health Insurance Service health screening test between 2008 and 2016. Mortality status was evaluated at the end of 2019. Participants were classified into normoglycemia, prediabetes, or diabetes mellitus (DM) categories. The duration of diabetes was noted in those with DM. This study focused on the association between glycemic status and all-cause mortality. Results The cohort, which was predominantly elderly (average age 75.1 years; 35.5% male), had a 35.2% mortality rate over an average 3.7-year follow-up. DM was linked with increased all-cause mortality risk (hazard ratio [HR] 1.34; 95% confidence interval [CI]: 1.32–1.37) compared to non-DM counterparts. The highest mortality risk was observed in long-term DM patients (≥ 5 years) (HR 1.43; 95% CI: 1.40–1.47), followed by newly diagnosed DM (HR 1.35; 95% CI: 1.30–1.40), shorter-term DM (

Abstract Although paediatric patients with gastrointestinal (GI) foreign bodies require multiple resources, they often present with few or no discernible symptoms and are typically assigned a low acuity level during triage. We compared the predictive accuracy of the revised Korean Triage and Acuity Scale (rKTAS), which elevates acuity by one step in relation to anticipated resource utilization, with that of the conventional KTAS for clinical outcomes. This was a retrospective study of National Emergency Department Information System data. Data on patient and ED characteristics, resources used, and clinical outcomes were collected from January 2018 to December 2021 for patients with GI foreign bodies aged under 19. The primary outcome was rKTAS accuracy in predicting hospitalization, ICU admission, operating room (OR) use, and ED length of stay (EDLOS). The AUROC was used to evaluate the performance via of the KTAS and rKTAS. In total, 25,324 paediatric patients visited the ED for GI tract foreign bodies. The mean age was 3.8 years, and 51% (12,923) were between 1 and 4 year old. Although most (23,658; 93.4%) were discharged, 4.9% required hospitalization. Two or more resources were utilized in 2514 (9.9%) cases, and 3,514 individuals had their triage levels increased by one step. Compared with those of the KTAS, the AUROCs of the rKTAS for predicting overall hospitalization (p

Objective This research investigated the effect of administering chromium (Cr) and meloxicam (MEL) on growth performance, cortisol and blood metabolite, and behaviors in young, regrouped heifers. Methods Fifty Holstein dairy heifers (body weight [BW] 198±32.7 kg and 6.5±0.82 months of age) were randomly assigned to non-regrouped group or four regrouped groups. Non-regrouped animals were held in the same pen throughout the entire experimental period (NL: non-regrouping and administration of lactose monohydrate [LM; placebo]). For regrouping groups, two or three heifers maintained in four different pens for 2 weeks were regrouped into a new pen and assigned to one of four groups: regrouping and LM administration (RL); regrouping and Cr administration (RC); regrouping and MEL administration (RM), and regrouping and Cr and MEL administration (RCM). LM (1 mg/kg BW), Cr (0.5 mg Cr picolinate/kg dry matter intake), and MEL (1 mg/kg BW) were orally administered immediately before regrouping. Blood was collected before regrouping (0 h) and at 3, 9, and 24 h and 7 and 14 d thereafter. Behaviors were recorded for 7 consecutive days after regrouping. Results Average daily gain was lower (p

The purpose of this study was to investigate the effect of the reflector, surface treatment, and length of scintillation crystals on the performance of a time-of-flight and depth-of-interaction (TOF-DOI) PET detector with a dual-ended readout and to determine the best reflector and surface treatment. Various types of crystal arrays with three different reflectors (ESR, BaSO4, and Toray), three different lateral surface treatments (all-polished (AP), all-roughened (AR), and partially roughened (PR, three sides polished, and one side roughened)), and two different lengths (20 and 15 mm) were fabricated. The highest light collection efficiency and best energy resolution were achieved using a crystal with a diffuse reflector (BaSO4 for AP and Toray for AR). In contrast, the best coincidence timing resolution (CTR) was achieved using an AR crystal with a specular reflector (ESR). The best DOI resolution was achieved using an AR crystal with BaSO4. Moreover, the results measured with the 20 mm long crystals were similar to those measured with the 15 mm long crystals. Therefore, we concluded that the dual-ended readout PET detector employing the crystal with AR lateral surface treatment and ESR was a good candidate for TOF-DOI PET because it provided excellent CTR and adequate DOI resolution.

Background Inconsistent results have been reported regarding the association between the use of antidiabetic drugs and the clinical outcomes of coronavirus disease 2019 (COVID-19). This study aimed to investigate the effect of antidiabetic drugs on COVID-19 outcomes in patients with diabetes using data from the National Health Insurance Service (NHIS) in South Korea. Methods We analyzed the NHIS data of patients aged ≥20 years who tested positive for COVID-19 and were taking antidiabetic drugs between December 2019 and June 2020. Multiple logistic regression analysis was performed to analyze the clinical outcomes of COVID-19 based on the use of antidiabetic drugs. Results A total of 556 patients taking antidiabetic drugs tested positive for COVID-19, including 271 male (48.7%), most of whom were in their sixties. Of all patients, 433 (77.9%) were hospitalized, 119 (21.4%) received oxygen treatment, 87 (15.6%) were admitted to the intensive care unit, 31 (5.6%) required mechanical ventilation, and 61 (11.0%) died. Metformin was significantly associated with the lower risks of mechanical ventilation (odds ratio [OR], 0.281; 95% confidence interval [CI], 0.109 to 0.720; P=0.008), and death (OR, 0.395; 95% CI, 0.182 to 0.854; P=0.018). Dipeptidylpeptidase-4 inhibitor (DPP-4i) were significantly associated with the lower risks of oxygen treatment (OR, 0.565; 95% CI, 0.356 to 0.895; P=0.015) and death (OR, 0.454; 95% CI, 0.217 to 0.949; P=0.036). Sulfonylurea was significantly associated with the higher risk of mechanical ventilation (OR, 2.579; 95% CI, 1.004 to 6.626; P=0.049). Conclusion In patients with diabetes and COVID-19, metformin exhibited reduced risks of mechanical ventilation and death, DPP-4i was linked with lower risks of oxygen treatment and death, while sulfonylurea was related to the increased risk of mechanical ventilation.

Abstract 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

Abstract Tobacco smoking (TS) is implicated in lung cancer (LC) progression through the development of metabolic syndrome. However, direct evidence linking metabolic syndrome to TS-mediated LC progression remains to be established. Our findings demonstrate that 4-(methylnitrosamino)−1-(3-pyridyl)−1-butanone and benzo[a]pyrene (NNK and BaP; NB), components of tobacco smoke, induce metabolic syndrome characteristics, particularly hyperglycemia, promoting lung cancer progression in male C57BL/6 J mice. NB enhances glucose uptake in tumor-associated macrophages by increasing the expression and surface localization of glucose transporter (GLUT) 1 and 3, thereby leading to transcriptional upregulation of insulin-like growth factor 2 (IGF2), which subsequently activates insulin receptor (IR) in LC cells in a paracrine manner, promoting its nuclear import. Nuclear IR binds to nucleophosmin (NPM1), resulting in IR/NPM1-mediated activation of the CD274 promoter and expression of programmed death ligand-1 (PD-L1). Restricting glycolysis, depleting macrophages, or blocking PD-L1 inhibits NB-mediated LC progression. Analysis of patient tissues and public databases reveals elevated levels of IGF2 and GLUT1 in tumor-associated macrophages, as well as tumoral PD-L1 and phosphorylated insulin-like growth factor 1 receptor/insulin receptor (pIGF-1R/IR) expression, suggesting potential poor prognostic biomarkers for LC patients. Our data indicate that paracrine IGF2/IR/NPM1/PD-L1 signaling, facilitated by NB-induced dysregulation of glucose levels and metabolic reprogramming of macrophages, contributes to TS-mediated LC progression.

Background and Purpose The accurate prediction of functional outcomes in patients with acute ischemic stroke (AIS) is crucial for informed clinical decision-making and optimal resource utilization. As such, this study aimed to construct an ensemble deep learning model that integrates multimodal imaging and clinical data to predict the 90-day functional outcomes after AIS. Methods We used data from the Korean Stroke Neuroimaging Initiative database, a prospective multicenter stroke registry to construct an ensemble model integrated individual 3D convolutional neural networks for diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), along with a deep neural network for clinical data, to predict 90-day functional independence after AIS using a modified Rankin Scale (mRS) of 3–6. To evaluate the performance of the ensemble model, we compared the area under the curve (AUC) of the proposed method with that of individual models trained on each modality to identify patients with AIS with an mRS score of 3–6. Results Of the 2,606 patients with AIS, 993 (38.1%) achieved an mRS score of 3–6 at 90 days post-stroke. Our model achieved AUC values of 0.830 (standard cross-validation [CV]) and 0.779 (time-based CV), which significantly outperformed the other models relying on single modalities: b-value of 1,000 s/mm2 (P

Assessing recurrent laryngeal nerve invasion is crucial for the accurate staging of thyroid cancer. This, in turn, determines the extent of surgery or whether active surveillance is appropriate. Ultrasonography is useful in diagnosing extrathyroidal extension to adjacent structures. However, preoperative ultrasound cannot definitely exclude recurrent laryngeal nerve invasion or identify the entire course of the recurrent laryngeal nerve to the thyroid gland. Therefore, it is important to understand the ultrasound features that are most likely to be associated with the gross involvement of the recurrent laryngeal nerve.

Background To investigate the prevalence, incidence, comorbidities, and management status of diabetic kidney disease (DKD) and diabetes-related end-stage kidney disease (ESKD) in South Korea. Methods We used the Korea National Health and Nutrition Examination Survey data (2019 to 2021, n=2,665) for the evaluation of prevalence, comorbidities, control rate of glycemia and comorbidities in DKD, and the Korean Health Insurance Service-customized database (2008 to 2019, n=3,950,857) for the evaluation of trends in the incidence and prevalence rate of diabetes-related ESKD, renin-angiotensin system (RAS) blockers and sodium glucose cotransporter 2 (SGLT2) inhibitors use for DKD, and the risk of atherosclerotic cardiovascular disease (ASCVD) and mortality according to DKD stages. DKD was defined as albuminuria or low estimated glomerular filtration rate (eGFR)

Abstract The effect of arterial tortuosity on intracranial atherosclerosis (ICAS) is not well understood. This study aimed to evaluate the effect of global intracranial arterial tortuosity on intracranial atherosclerotic burden in patients with ischemic stroke. We included patients with acute ischemic stroke who underwent magnetic resonance angiography (MRA) and classified them into three groups according to the ICAS burden. Global tortuosity index (GTI) was defined as the standardized mean curvature of the entire intracranial arteries, measured by in-house vessel analysis software. Of the 516 patients included, 274 patients had no ICAS, 140 patients had a low ICAS burden, and 102 patients had a high ICAS burden. GTI increased with higher ICAS burden. After adjustment for age, sex, vascular risk factors, and standardized mean arterial area, GTI was independently associated with ICAS burden (adjusted odds ratio [adjusted OR] 1.33; 95% confidence interval [CI] 1.09–1.62). The degree of association increased when the arterial tortuosity was analyzed limited to the basal arteries (adjusted OR 1.48; 95% CI 1.22–1.81). We demonstrated that GTI is associated with ICAS burden in patients with ischemic stroke, suggesting a role for global arterial tortuosity in ICAS.

Abstract This study investigated the potential associations between allergic diseases (asthma, allergic rhinitis, and atopic dermatitis) and the development of primary open-angle glaucoma. We utilized authorized data from the Korean National Health Information Database (KNHID), which provides comprehensive medical claims data and information from the National Health Screening Program. We compared the baseline characteristics of subjects with and without allergic diseases and calculated the incidence and risk of glaucoma development. Cox proportional hazard regression analysis was used to determine the risk of glaucoma development in subjects with allergic diseases. A total of 171,129 subjects aged 20–39 with or without allergic diseases who underwent a general health examination between 2009 and 2015 were included. Subjects with allergic diseases exhibited a higher incidence of glaucoma compared to the control group. The hazard ratio (HR) of glaucoma onset was 1.49 and 1.39 in subjects with at least one allergic disease before and after adjusting for potential confounding factors, respectively. Among allergic diseases, atopic dermatitis showed the highest risk for glaucoma development (aHR 1.73) after adjusting for confounders. Allergic rhinitis showed an increased risk for incident glaucoma after adjustment (aHR 1.38). Asthma showed the lowest but still increased risk for glaucoma (aHR 1.22). The associations were consistent in all subgroup analyses stratified by sex, smoking, drinking, exercise, diabetes, hypertension, dyslipidemia, or history of steroid. In conclusion, allergic diseases are associated with increased risk of glaucoma development. Among allergic diseases, atopic dermatitis showed the highest risk for glaucoma development followed by allergic rhinitis and asthma.

Abstract Purpose Satisfaction should be prioritized to maximize the value of education for trainees. This study was conducted with professors, fellows, and surgical residents in the Department of general surgery (GS) to evaluate the importance of various educational modules to surgical residents. Methods A questionnaire was administered to professors (n = 28), fellows (n = 8), and surgical residents (n = 14), and the responses of the three groups were compared. Four different categories of educational curricula were considered: instructor-led training, clinical education, self-paced learning, and hands-on training. Results The majority of surgeons regarded attending scrubs as the most important educational module in the training of surgical residents. However, while professors identified assisting operators by participating in surgery as the most important, residents assessed the laparoscopic training module with animal models as the most beneficial. Conclusions The best educational training course for surgical residents was hands-on training, which would provide them with several opportunities to operate and perform surgical procedures themselves.

Abstract Objectives We primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors. Methods We retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs. Results A total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p

Abstract Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (TAMR) breast cancer and its potential interplay with the tumor microenvironment (TME). TAMR breast cancer cell lines TAMR-V and TAMR-H were compared with the luminal type A cell line (MCF-7). LncRNA expression was assessed via next-generation sequencing, RNA extraction, lncRNA profiling, and quantitative RT-qPCR. SOX2OT overexpression effects on cell proliferation, migration, and invasion were evaluated using various assays. SOX2OT was consistently downregulated in TAMR cell lines and TAMR breast cancer tissue. Overexpression of SOX2OT in TAMR cells increased cell proliferation and cell invasion. However, SOX2OT overexpression did not significantly alter SOX2 levels, suggesting an independent interaction within TAMR cells. Kaplan–Meier plot analysis revealed an inverse relationship between SOX2OT expression and prognosis in luminal A and B breast cancers. Our findings highlight the potential role of SOX2OT in TAMR breast cancer progression. The downregulation of SOX2OT in TAMR breast cancer indicates its involvement in resistance mechanisms. Further studies should explore the intricate interactions between SOX2OT, SOX2, and TME in breast cancer subtypes.

Time-of-flight (TOF) PET detectors with fast-rise-time scintillators and fast-single photon time resolution silicon photomultiplier (SiPM) have been developed to improve the coincidence timing resolution (CTR) to sub-100 ps. The CTR can be further improved with an optimal bandwidth and minimized electronic noise in the readout circuit and this helps reduce the distortion of the fast signals generated from the TOF-PET detector. The purpose of this study was to develop an ultra-high frequency and fully-differential (UF-FD) readout circuit that minimizes distortion in the fast signals produced using TOF-PET detectors, and suppresses the impact of the electronic noise generated from the detector and front-end readout circuits. The proposed UF-FD readout circuit is composed of two differential amplifiers (time) and a current feedback operational amplifier (energy). The ultra-high frequency differential (7 GHz) amplifiers can reduce the common ground noise in the fully-differential mode and minimize the distortion in the fast signal. The CTR and energy resolution were measured to evaluate the performance of the UF-FD readout circuit. These results were compared with those obtained from a high-frequency and single ended readout circuit. The experiment results indicated that the UF-FD readout circuit proposed in this study could substantially improve the best achievable CTR of TOF-PET detectors.

Abstract is missing (Short communication)

Background Atrial fibrillation detected after stroke (AFDAS) refers to the identification of newly diagnosed atrial fibrillation (AF) following an ischemic stroke in patients without known AF (KAF). The objective of this study was to compare the functional outcomes of patients diagnosed with AFDAS and those with KAF who underwent mechanical thrombectomy. Methods and Results We conducted a retrospective analysis of patients who underwent mechanical thrombectomy and with either new AF diagnosed during hospitalization or KAF. We compared the baseline characteristics, clinical, and procedure‐related variables between those with AFDAS and KAF. The primary outcome was the achievement of functional independence, defined as a modified Rankin Scale score of 0 to 2, at 3 months after stroke. Of the 252 patients, 101 (40.1%) were classified into the AFDAS group. The KAF group exhibited a higher rate of stroke history compared with the AFDAS group (32.5% versus 13.9%; P=0.001). Tandem occlusion was more common in the KAF group (13.2% versus 5.9%), while M2 occlusion was more common in the AFDAS group (11.3% versus 20.8%). The proportion of patients who achieved functional independence was higher in the AFDAS group (37.7% versus 52.5%; P=0.029). Multivariable analysis showed that AFDAS was associated with a favorable functional outcome (odds ratio, 2.67 [95% CI, 1.39–5.14]; P=0.003). Conclusions AFDAS demonstrated a positive association with functional independence in patients with stroke who underwent mechanical thrombectomy and were finally diagnosed to have AF during hospitalization. The observed disparities in occlusion site, intractable thrombus, and history of previous stroke may have contributed to these findings.

BackgroundData-driven digital learning could improve the diagnostic performance of novice students for thyroid nodules.ObjectiveTo evaluate the efficacy of digital self-learning and artificial intelligence-based computer-assisted diagnosis (AI-CAD) for inexperienced readers to diagnose thyroid nodules.MethodsBetween February and August 2023, a total of 26 readers (less than 1 year of experience in thyroid US from various departments) from 6 hospitals participated in this study. Readers completed an online learning session comprising 3,000 thyroid nodules annotated as benign or malignant independently. They were asked to assess a test set consisting of 120 thyroid nodules with known surgical pathology before and after a learning session. Then, they referred to AI-CAD and made their final decisions on the thyroid nodules. Diagnostic performances before and after self-training and with AI-CAD assistance were evaluated and compared between radiology residents and readers from different specialties.ResultsAUC (area under the receiver operating characteristic curve) improved after the self-learning session, and it improved further after radiologists referred to AI-CAD (0.679 vs 0.713 vs 0.758, p

Hikikomori syndrome (HS), a phenomenon characterized by social withdrawal and isolation, has attracted significant attention in both academic and clinical settings. However, understanding the diverse nature of HS remains a challenge due to its multifaceted etiology and presentation. This paper aims to shed light on this phenomenon by examining three representative typologies of HS in clinical settings. Through detailed case analyses, we categorize HS into three main types: HS associated with neurodevelopmental disorders; HS triggered by the onset of mental illness; and HS emerging gradually with age-related challenges. By elucidating these typologies, we provide insights into the complex interplay of psychological, social, and developmental factors contributing to HS, thereby facilitating more tailored approaches for the evaluation of and intervention into this syndrome in clinical practice.

Background : The 2023 Obesity Fact Sheet aims to present an updated overview of obesity prevalence across all age groups, including children and adolescents. Methods : This study included individuals aged ≥20 years (n=16,941,423 in 2021) who underwent health checkups provided by the Korean National Health Insurance Service between 2012 and 2021. The prevalence of obesity and abdominal obesity was standardized by age and sex using data from the 2010 population and housing census. For children and adolescents (6 to 18 years) (n=884 in 2021), we used the Korea National Health and Nutrition Examination Survey (2012 to 2021), and obesity was defined by the corresponding sex- and age-specific body mass index percentile of 95th or greater based on the 2017 Korean National Growth Chart for Children and Adolescents. Results : The overall prevalence of obesity in 2021 is 38.4% (49.2% in men and 27.8% in women), which is a 1.27-fold increase from 30.2% in 2012. The prevalence of obesity has increased across all age groups, particularly among those aged 20, 30, and 80 years. The prevalence of class III obesity substantially increased from 0.35% (men) and 0.42% (women) in 2012 to 1.21% and 0.97% in 2021, with 3.46- and 2.31-fold increases, respectively. This increase was particularly pronounced in young adults. The prevalence of obesity in children and adolescents has surged from 9.7% in 2012 to 19.3% in 2021, with a greater increase among boys. Conclusion : Our study provides information on the current status of obesity prevalence based on the 2023 Obesity Fact Sheet, emphasizing the urgency of implementing timely strategies to reverse this increasing trend.

AIM: In this study, we use Artificial Intelligence (AI), including Machine (ML) and Deep Learning (DL), to predict the long-term survival of resectable esophageal cancer (EC) patients in a high-volume surgical center. Our objective is to evaluate the predictive efficacy of AI methods for survival prognosis across different time points of oncological treatment. This involves comparing models trained with clinical data, integrating either Tumor, Node, Metastasis (TNM) classification or tumor biomarker analysis, for long-term survival predictions. METHODS: In this retrospective study, 1002 patients diagnosed with EC between 1996 and 2021 were analyzed. The original dataset comprised 55 pre- and postoperative patient characteristics and 55 immunohistochemically evaluated biomarkers following surgical intervention. To predict the five-year survival status, four AI methods (Random Forest RF, XG Boost XG, Artificial Neural Network ANN, TabNet TN) and Logistic Regression (LR) were employed. The models were trained using three predefined subsets of the training dataset as follows: (I) the baseline dataset (BL) consisting of pre-, intra-, and postoperative data, including the TNM but excluding tumor biomarkers, (II) clinical data accessible at the time of the initial diagnostic workup (primary staging dataset, PS), and (III) the PS dataset including tumor biomarkers from tissue microarrays (PS + biomarkers), excluding TNM status. We used permutation feature importance for feature selection to identify only important variables for AI-driven reduced datasets and subsequent model retraining. RESULTS: Model training on the BL dataset demonstrated similar predictive performances for all models (Accuracy, ACC: 0.73/0.74/0.76/0.75/0.73; AUC: 0.78/0.82/0.83/0.80/0.79 RF/XG/ANN/TN/LR, respectively). The predictive performance and generalizability declined when the models were trained with the PS dataset. Surprisingly, the inclusion of biomarkers in the PS dataset for model training led to improved predictions (PS dataset vs. PS dataset + biomarkers; ACC: 0.70 vs. 0.77/0.73 vs. 0.79/0.71 vs. 0.75/0.69 vs. 0.72/0.63 vs. 0.66; AUC: 0.77 vs. 0.83/0.80 vs. 0.85/0.76 vs. 0.86/0.70 vs. 0.76/0.70 vs. 0.69 RF/XG/ANN/TN/LR, respectively). The AI models outperformed LR when trained with the PS datasets. The important features shared after AI-driven feature selection in all models trained with the BL dataset included histopathological lymph node status (pN), histopathological tumor size (pT), clinical tumor size (cT), age at the time of surgery, and postoperative tracheostomy. Following training with the PS dataset with biomarkers, the important predictive features included patient age at the time of surgery, TP-53 gene mutation, Mesothelin expression, thymidine phosphorylase (TYMP) expression, NANOG homebox protein expression, and indoleamine 2,3-dioxygenase (IDO) expressed on tumor-infiltrating lymphocytes, as well as tumor-infiltrating Mast- and Natural killer cells. CONCLUSION: Different AI methods similarly predict the long-term survival status of patients with EC and outperform LR, the state-of-the-art classification model. Survival status can be predicted with similar predictive performance with patient data at an early stage of treatment when utilizing additional biomarker analysis. This suggests that individual survival predictions can be made early in cancer treatment by utilizing biomarkers, reducing the necessity for the pathological TNM status post-surgery. This study identifies important features for survival predictions that vary depending on the timing of oncological treatment.

Abstract This study aimed to investigate the association between nonarteritic anterior ischemic optic neuropathy (NAION) and Parkinson's disease (PD) using a retrospective, nationwide, population-based cohort in South Korea. This study utilized data from the Korean National Health Insurance database, including 43,960 NAION patients and 219,800 age- and sex-matched controls. Cox proportional hazards regression models were used to assess the risk of developing PD in the NAION group compared to the control group after adjusting for various confounding factors. Subgroup analyses were conducted based on sex, age, and comorbidities. The incidence rate of PD was higher in the NAION group (1.326 per 1000 person-years) than in the control group (0.859 per 1000 person-years). After adjusting for confounding factors, the risk of developing PD was significantly higher in the NAION group (adjusted hazard ratio [aHR] 1.516, 95% confidence interval [CI] 1.300–1.769). Subgroup analyses did not reveal a significant difference in the risk of PD development based on sex, age, or comorbidities. This retrospective, nationwide, population-based cohort study revealed a significant association between NAION and an increased risk of developing PD in a South Korean population. The incidence rate of PD was observed to be higher in individuals diagnosed with NAION than in age- and sex-matched controls even after adjusting for potential confounding variables, with the risk being approximately 51.6% higher in the NAION group. Further research is necessary to elucidate the underlying pathophysiological mechanisms linking NAION to PD and to determine whether similar associations exist in other ethnic and geographical populations.

Docetaxel (DTX), a semi-synthetic analogue of paclitaxel (taxol), is known to exert potent anticancer activity in various cancer cells by suppressing normal microtubule dynamics. In this study, we examined how the anticancer effect of DTX is regulated by polyphenols extracted from Korean Artemisia annua L. (pKAL) in DU145 prostate cancer cells (mutant p53) and HCT116 colorectal cancer cells (wild-type p53). Here, we show that the anticancer effect of DTX was enhanced more significantly by pKAL in HCT116 cells than in DU145 cells via phase-contrast microscopy, CCK-8 assay, Western blot, and flow cytometric analysis of annexin V/propidium iodide-stained cells. Notably, mutant p53 was slightly downregulated by single treatment of pKAL or DTX in DU145 cells, whereas wild-type p53 was significantly upregulated by pKAL or DTX in HCT116 cells. Moreover, the enhanced anticancer effect of DTX by pKAL in HCT116 cells was significantly associated with the suppression of DTX-induced p53 upregulation, increase of DTX-induced phospho-p38, and decrease of DTX-regulated cyclin A, cyclin B1, AKT, caspase-8, PARP1, GM130, NF-κB p65, and LDHA, leading to the increased apoptotic cell death and plasma membrane permeability. Our results suggest that pKAL could effectively improve the anticancer effect of DTX-containing chemotherapy used to treat various cancers expressing wild-type p53.

Background: Concern has been growing regarding post-tuberculosis (TB) morbidities, including neurologic and vascular comorbidities. However, the association between post-TB status and the risk of dementia has been evaluated in only few studies. Therefore, in the present study, the risk of dementia was investigated in a nationwide population-based cohort. Methods: Using the Korean National Health Insurance Service (KNHIS) database, this study included TB survivors (n = 50,182) and matched controls (n = 50,182) for age, sex, and year of index date. The risk of dementia was estimated using Cox proportional hazards regression, and stratified analyses for related factors were performed. Results: During a mean 3.5 years of follow-up, the incidence of dementia was 9.32 for Alzheimer disease and 1.17 for vascular dementia per 1000 person-years for TB survivors and 7.21 and 0.67, respectively, for matched controls. The overall risk of Alzheimer disease was 1.11 (95% confidence interval (CI) 1.03–1.20)-fold higher in TB survivors than in matched controls. For vascular dementia, 1.48 (95% CI 1.16–1.89)-fold higher risk was found in TB survivors than in matched controls. The strength of the association between TB and dementia was higher in CNS TB (aHR 1.76, 95% CI 1.18 –2.64) than non-CNS TB (aHR 1.11, 95% CI 1.05–1.19) compared to controls, especially for patients with vascular dementia (3.33, 95% CI 1.06–10.49). Conclusion: TB survivors had a significantly higher risk of dementia than the general population.

Abstract Patients with dementia with Lewy bodies (DLB) show widespread brain metabolic changes. This study investigated whether brain hypo- and hypermetabolism in DLB have differential effects on cognition. We enrolled 55 patients with DLB (15 prodromal DLB [MCI-LB] and 40 probable DLB) and 13 healthy controls who underwent 18F-fluorodeoxyglucose positron emission tomography and detailed neuropsychological tests. Metabolic indices reflecting associated changes in regional cerebral glucose metabolism were calculated as follows: index(-) for hypometabolism [DLB-hypo] and index(+) for hypermetabolism [DLB-hyper]. The effects of DLB-hypo or DLB-hyper on cognitive function were assessed using a multivariate linear regression model. Additionally, a linear mixed model was used to investigate the association between each index and the longitudinal cognitive decline. There was no correlation between DLB-hypo and DLB-hyper in the disease group. The multivariate linear regression model showed that DLB-hypo was associated with language, visuospatial, visual memory, and frontal/executive functions; whereas DLB-hyper was responsible for attention and verbal memory. There was significant interaction between DLB-hypo and DLB-hyper for verbal and visual memory, which was substantially affected by DLB-hyper in relatively preserved DLB-hypo status. A linear mixed model showed that DLB-hypo was associated with longitudinal cognitive outcomes, regardless of cognitive status, and DLB-hyper contributed to cognitive decline only in the MCI-LB group. The present study suggests that DLB-hypo and DLB-hyper may be independent of each other and differentially affect the baseline and longitudinal cognitive function in patients with DLB.

Abstract Background The increased expression of the nicotinic acetylcholine receptor (nAChR) in muscle denervation is thought to be associated with electrophysiological acetylcholine supersensitivity after nerve injury. Hence, we investigated the utility of the 18F-ASEM alpha7-nAChR targeting radiotracer as a new diagnostic method by visualizing skeletal muscle denervation in mouse models of sciatic nerve injury. Methods Ten-week-old C57BL/6 male mice were utilized. The mice were anesthetized, and the left sciatic nerve was resected after splitting the gluteal muscle. One week (n = 11) and three weeks (n = 6) after the denervation, 18F-ASEM positron emission tomography/magnetic resonance imaging (PET/MRI) was acquired. Maximum standardized uptake values (SUVmax) of the tibialis anterior muscle were measured for the denervated side and the control side. Autoradiographic evaluation was performed to measure the mean counts of the denervated and control tibialis anterior muscles at one week. In addition, immunohistochemistry was used to identify alpha7-nAChR-positive areas in denervated and control tibialis anterior muscles at one week (n = 6). Furthermore, a blocking study was conducted with methyllycaconitine (MLA, n = 5). Results 18F-ASEM PET/MRI showed significantly increased 18F-ASEM uptake in the denervated tibialis anterior muscle relative to the control side one week and three weeks post-denervation. SUVmax of the denervated muscles at one week and three weeks showed significantly higher uptake than the control (P = 0.0033 and 0.0277, respectively). The relative uptake by autoradiography for the denervated muscle was significantly higher than in the control, and immunohistochemistry revealed significantly greater alpha7-nAChR expression in the denervated muscle (P = 0.0277). In addition, the blocking study showed no significant 18F-ASEM uptake in the denervated side when compared to the control (P = 0.0796). Conclusions Our results suggest that nAChR imaging with 18F-ASEM has potential as a noninvasive diagnostic method for peripheral nervous system disorders.

Abstract Background Cholesterol is an essential component of the neuronal cell membrane and is crucial for neuronal function; however, the role of cholesterol levels in Parkinson’s disease (PD) is debatable. This study investigated the complex relationship between total cholesterol (TC) levels, body mass index (BMI), and cognition in patients with PD. Methods This study included 321 drug-naïve patients with PD who underwent dopamine transporter (DAT) imaging and baseline neuropsychological tests. Multivariate linear regression and Cox regression models were used to investigate the effect of TC levels on the composite score of each cognitive domain and dementia conversion after adjusting for covariates, respectively. Interaction analyses were performed to examine the interaction effect between TC levels and BMI on baseline cognition and dementia conversion. Results TC levels and cognition showed no significant relationship after adjusting for potential confounders. A significant interaction effect between TC levels and BMI was observed in frontal/executive function and dementia conversion. Further analyses showed that TC levels were positively associated with frontal/executive function in the under-/normal weight group (β = 0.205, p = 0.013), whereas a negative relationship existed between TC levels and frontal/executive function in the obese group (β = − 0.213, p = 0.017). Cox regression analyses also showed the differential effects of TC levels on dementia conversion according to BMI (under-/normal weight group: hazard ratio [HR] = 0.550, p = 0.013; obese group: HR = 2.085, p = 0.014). Conclusions This study suggests a cross-over interaction between TC levels and BMI on cognitive symptoms in PD.

Background This cohort study aims to examine the relationship between the occurrence of cranial nerve palsy (CNP) affecting the third, fourth, or sixth cranial nerve and the subsequent risk of stroke, with a particular focus on the modulating effect of age on this association. Methods and Results We established a cohort of individuals diagnosed with third, fourth, or sixth CNP who underwent national health screening within 2 years of diagnosis from 2010 to 2017. A control group was matched by sex and age at a ratio of 1:5. Participants were followed until December 31, 2019. We use multivariable Cox proportional hazards regression analyses to assess the association between ocular motor CNP and subsequent stroke stratified by age. Covariates including lifestyle, health behavior, underlying comorbidities, and Charlson comorbidity index score were also adjusted. Compared with the control group, the ocular motor CNP group had a higher risk of stroke after adjusting for potential confounders (hazard ratio [HR], 1.23 [95% CI,, 1.08–1.39]). The risk of stroke increased by 8.91 times in individuals with ocular motor CNP who were in their 30s (HR, 8.91 [95% CI, 1.63–48.66]). The risk increased by 2.49 times in those who were in their 40s, 1.78 times in those who were in their 50s, and 1.32 times in those who were in their 60s (HRs, 2.49, 1.78, and 1.32 [95% CI, 1.39–4.45, 1.31–2.42, and 1.08–1.62], respectively). However, for those who were in their 20s, 70s, or 80s, the incidence of stroke did not significantly increase. Conclusions Our study establishes an association between ocular motor CNP and an increased risk of stroke, particularly in young adults.

Abstract Hexagonal boron nitride (h‐BN) is a key ingredient for various 2D van der Waals heterostructure devices, but the exact role of h‐BN encapsulation in relation to the internal defects of 2D semiconductors remains unclear. Here, it is reported that h‐BN encapsulation greatly removes the defect‐related gap states by stabilizing the chemisorbed oxygen molecules onto the defects of monolayer WS2 crystals. Electron energy loss spectroscopy (EELS) combined with theoretical analysis clearly confirms that the oxygen molecules are chemisorbed onto the defects of WS2 crystals and are fixated by h‐BN encapsulation, with excluding a possibility of oxygen molecules trapped in bubbles or wrinkles formed at the interface between WS2 and h‐BN. Optical spectroscopic studies show that h‐BN encapsulation prevents the desorption of oxygen molecules over various excitation and ambient conditions, resulting in a greatly lowered and stabilized free electron density in monolayer WS2 crystals. This suppresses the exciton annihilation processes by two orders of magnitude compared to that of bare WS2. Furthermore, the valley polarization becomes robust against the various excitation and ambient conditions in the h‐BN encapsulated WS2 crystals.

PurposeTuberculosis (TB) is linked to sustained inflammation even after treatment, and fracture risk is higher in TB survivors than in the general population. However, no individualized fracture risk prediction model exists for TB survivors. We aimed to estimate fracture risk, identify fracture-related factors, and develop an individualized risk prediction model for TB survivors.MethodsTB survivors (n = 44,453) between 2010 and 2017 and 1:1 age- and sex-matched controls were enrolled. One year after TB diagnosis, the participants were followed-up until the date of fracture, death, or end of the study period (December 2018). Cox proportional hazard regression analyses were performed to compare the fracture risk between TB survivors and controls and to identify fracture-related factors among TB survivors.ResultsDuring median 3.4 (interquartile range, 1.6–5.3) follow-up years, the incident fracture rate was significantly higher in TB survivors than in the matched controls (19.3 vs. 14.6 per 1,000 person-years, p

Abstract Background Despite multiple therapeutic modalities, the overall survival of patients with gastric adenocarcinoma remains poor, especially for advanced tumor stages. Although the tyrosine kinase MerTK has shown therapeutic relevance in several tumor entities, its potential effects in gastric adenocarcinoma have not yet been sufficiently characterized. Methods MerTK expression and its influence on patient survival were evaluated by immunohistochemistry in a cohort of 140 patients with gastric adenocarcinoma. CRISPR/Cas9 knockout and siRNA knockdown of MerTK in the gastric cancer cell lines SNU1, SNU5, and MKN45 was used to analyze protein expression, growth, migration, and invasion properties in vitro and in a murine xenograft model. MerTK was pharmacologically targeted with the small molecule inhibitor UNC2025 in vitro and in vivo. Results In patients, high MerTK expression was associated with decreased overall survival (OS) and lymph node metastasis especially in patients without neoadjuvant therapy (p

Stroke is a leading cause of disability and death. The condition requires prompt diagnosis and treatment. The quality of care provided to patients with stroke can vary depending on the availability of medical resources, which in turn, can affect prognosis. Recently, there has been growing interest in using machine learning (ML) to support stroke diagnosis and treatment decisions based on large medical data sets. Current ML applications in stroke care can be divided into two categories: analysis of neuroimaging data and clinical informationbased predictive models. Using ML to analyze neuroimaging data can increase the efficiency and accuracy of diagnoses. Commercial software that uses ML algorithms is already being used in the medical field. Additionally, the accuracy of predictive ML models is improving with the integration of radiomics and clinical data. is expected to be important for improving the quality of care for patients with stroke.

Objective Although several studies have reported successful fusion rates after oblique lumbar interbody fusion (OLIF) using allografts or dimerized bone matrix (DBM) instead of autografts, whether OLIF can achieve satisfactory solid fusion without the use of autografts remains unclear. This study investigated the real fusion rates after OLIF using allografts and DBM, which were evaluated using both dynamic radiographs and computed tomography scans. Methods We enrolled 79 consecutive patients who underwent minimally invasive OLIF followed by percutaneous pedicle screw fixation. All patients were treated with OLIF between L2 and L5 and underwent radiographic and clinical follow-ups at 12, 18, and 24 months after surgery. Radiographic assessment of fusion was performed using the modified BrantigaSteffee-Fraser (mBSF) scale, which was categorized as follows: grades I (radiographic pseudoarthrosis), II (indeterminate fusion), and III (solid radiographic fusion). Other radiologic and clinical outcomes were evaluated using the following parameters: vertebral slippage distance, disc height, subsidence, Oswestry Disability Index (ODI), and visual analogue scale (VAS). Results Clinical outcomes demonstrated significant improvements in the VAS scores for back pain, leg pain, and ODI after surgery. Subsidence was present in 34 cases (35.4%) at 12 months postoperatively, which increased to 47.9% and reached 50.0% at 1.5 years and 2 years after surgery, respectively. The solid fusion rate after OLIF was 32.3% at 1 year, increased to 58.3% at 1.5 years, and reached 72.9% at 2 years. Radiographic pseudoarthrosis was 24.0% at 1 year, which decreased to 6.3% at 1.5 years and 3.1% at 2 years. Conclusion OLIF is a safe and effective surgical procedure for the treatment of degenerative lumbar diseases. The mBSF scale, which simultaneously evaluates both dynamic angles and bone bridge formation, offers great reliability for the radiological assessment of fusion. Moreover, OLIF using allografts and DBM, which is performed on one or 2 levels at L2–5, can achieve satisfactory fusion rates within 2 years after surgery.

Abstract In this paper, we propose a deep-learning-based algorithm for screening neurological diseases. We proposed various examination protocols for screening neurological diseases and collected data by video-recording persons performing these protocols. We converted video data into human landmarks that capture action information with a much smaller data dimension. We also used voice data which are also effective indicators of neurological disorders. We designed a subnetwork for each protocol to extract features from landmarks or voice and a feature aggregator that combines all the information extracted from the protocols to make a final decision. Multitask learning was applied to screen two neurological diseases. To capture meaningful information about these human landmarks and voices, we applied various pre-trained models to extract preliminary features. The spatiotemporal characteristics of landmarks are extracted using a pre-trained graph neural network, and voice features are extracted using a pre-trained time-delay neural network. These extracted high-level features are then passed onto the subnetworks and an additional feature aggregator that are simultaneously trained. We also used various data augmentation techniques to overcome the shortage of data. Using a frame-length staticizer that considers the characteristics of the data, we can capture momentary tremors without wasting information. Finally, we examine the effectiveness of different protocols and different modalities (different body parts and voice) through extensive experiments. The proposed method achieves AUC scores of 0.802 for stroke and 0.780 for Parkinson’s disease, which is effective for a screening system.

Abstract Background The association between systemic sclerosis and the development of bronchiectasis is unclear. This study aimed to compare the risk of bronchiectasis between individuals with systemic sclerosis and those without using a nationwide longitudinal dataset. Methods Using the Korean National Health Insurance Service dataset between 2010 and 2017, we identified 4845 individuals aged ≥ 20 years with systemic sclerosis and 24,225 without systemic sclerosis who were matched 1:5 by age and sex. They were followed up until the date of a bronchiectasis diagnosis, death, or December 31, 2019, whichever came first. Results During a median follow-up period of 6.0 (interquartile range, 3.2–8.7) years, 5.3% of the systemic sclerosis cohort and 1.9% of the matched cohort developed bronchiectasis, with incidence rates of 9.99 and 3.23 per 1000 person-years, respectively. Even after adjusting for potential confounders, the risk of incident bronchiectasis was significantly higher in the systemic sclerosis cohort than in the matched cohort (adjusted hazard ratio 2.63, 95% confidence interval 2.22–3.12). A subgroup analysis of individuals with systemic sclerosis revealed that the risk of incident bronchiectasis was notably higher in younger individuals aged 20–39 years (P for interaction = 0.048) and in those without other coexisting connective tissue diseases (P for interaction = 0.006) than in their counterparts. Conclusions The risk of incident bronchiectasis is higher in individuals with systemic sclerosis than those without. Bronchiectasis should be considered one of the pulmonary manifestations related to systemic sclerosis.

ROV operators often encounter challenges with orientation awareness while operating underwater, primarily due to relying solely on 2D camera feeds to manually control the ROV robot arm. This limitation in underwater visibility and orientation awareness, as observed among Malaysian ROV operators, can compromise the accuracy of arm placement, and pose a risk of tool damage if not handle with care. To address this, a 3D orientation monitoring system for ROVs has been developed, leveraging measurement sensors with nine degrees of freedom (DOF). These sensors capture crucial parameters such as roll, pitch, yaw, and heading, providing real-time data on the ROV’s position along the X, Y, and Z axes to ensure precise orientation. These data are then utilized to generate and process 3D imaging and develop a corresponding 3D model of the operational ROV underwater, accurately reflecting its orientation in a visual representation by using an open-source platform. Due to constraints set by an agreement with the working class ROV operators, only short-term tests (up to 1 min) could be performed at the dockyard. A video demonstration of a working class ROV replica moving and reflecting in a 3D simulation in real-time was also presented. Despite these limitations, our findings demonstrate the feasibility and potential of a cost-effective 3D orientation visualization system for working class ROVs. With mean absolute error (MAE) error less than 2%, the results align with the performance expectations of the actual working ROV.

Background: The aim of this study was to establish a deep learning prediction model for neoadjuvant FLOT chemotherapy response. The neural network utilized clinical data and visual information from whole-slide images (WSIs) of therapy-naïve gastroesophageal cancer biopsies. Methods: This study included 78 patients from the University Hospital of Cologne and 59 patients from the University Hospital of Heidelberg used as external validation. Results: After surgical resection, 33 patients from Cologne (42.3%) were ypN0 and 45 patients (57.7%) were ypN+, while 23 patients from Heidelberg (39.0%) were ypN0 and 36 patients (61.0%) were ypN+ (p = 0.695). The neural network had an accuracy of 92.1% to predict lymph node metastasis and the area under the curve (AUC) was 0.726. A total of 43 patients from Cologne (55.1%) had less than 50% residual vital tumor (RVT) compared to 34 patients from Heidelberg (57.6%, p = 0.955). The model was able to predict tumor regression with an error of ±14.1% and an AUC of 0.648. Conclusions: This study demonstrates that visual features extracted by deep learning from therapy-naïve biopsies of gastroesophageal adenocarcinomas correlate with positive lymph nodes and tumor regression. The results will be confirmed in prospective studies to achieve early allocation of patients to the most promising treatment.

The first seven months of the US COVID-19 pandemic saw a massive increase in COVID-19-related crowdfunding campaigns. Despite their popularity, these campaigns were rarely successful in reaching their monetary goals, with nearly 40% of them not receiving a single donation. Previous research has indicated that crowdfunding has increased inequities and disparities in wealth, and this study set out to examine the situation in Washington State, an area greatly divided socio-economically, culturally, and geographically. Using GIS-based Multi-Criteria Evaluation (MCE) models with Quantile classification, we created geospatial representations of composite independent variables representing the impacts of COVID-19 and social marginalization on Washington state counties. We then examined the relationships between these variables with the dependent variables, campaign prevalence and outcome (campaign median amount raised), and assessed for relationships through ANOVA tests. These representations allowed us to assess the possibility that both COVID-19 impact and social marginalization may be amplifying already present inequities in Washington state by influencing crowdfunding monetary outcomes and prevalence. Our research indicates that county-wide social marginalization is associated with COVID-19-related crowdfunding campaign prevalence, generally pointing towards counties with lower social marginalization producing more campaigns. We also found that COVID-19 impact is, surprisingly, not associated with campaign prevalence, and that there was no relationship between campaign outcome and marginalization or COVID-19 impact. These findings indicate that inequitable access to, and use of, technologies like crowdfunding may be further contributing to COVID-19 inequities within Washington state. Policy-makers should be advised to use crowdfunding information with extreme caution when considering it as a useful tool in assessing community needs within counties and allocating resources, because those with the highest need likely are not being represented in this data due to lack of access.

Abstract Systematic optimization of the photocatalyst and investigation of the role of each component is important to maximizing catalytic activity and comprehending the photocatalytic conversion of CO2 reduction to solar fuels. A surface‐modified Ag@Ru‐P25 photocatalyst with H2O2 treatment was designed in this study to convert CO2 and H2O vapor into highly selective CH4. Ru doping followed by Ag nanoparticles (NPs) cocatalyst deposition on P25 (TiO2) enhances visible light absorption and charge separation, whereas H2O2 treatment modifies the surface of the photocatalyst with hydroxyl (–OH) groups and promotes CO2 adsorption. High‐resonance transmission electron microscopy, X‐ray photoelectron spectroscopy, X‐ray absorption near‐edge structure, and extended X‐ray absorption fine structure techniques were used to analyze the surface and chemical composition of the photocatalyst, while thermogravimetric analysis, CO2 adsorption isotherm, and temperature programmed desorption study were performed to examine the significance of H2O2 treatment in increasing CO2 reduction activity. The optimized Ag1.0@Ru1.0‐P25 photocatalyst performed excellent CO2 reduction activity into CO, CH4, and C2H6 with a ~95% selectivity of CH4, where the activity was ~135 times higher than that of pristine TiO2 (P25). For the first time, this work explored the effect of H2O2 treatment on the photocatalyst that dramatically increases CO2 reduction activity.

Purpose: This analysis aimed to characterize the exposure–response relationship of bevacizumab in non-small-cell lung cancer (NSCLC) and evaluate the efficacy of SB8, a bevacizumab biosimilar, and Avastin®, the reference bevacizumab sourced from the European Union (EU), based on the exposure reported in a comparative phase III efficacy and safety study (EudraCT, 2015-004026-34; NCT 02754882).Materials and methods: The overall survival (OS) and progression-free survival (PFS) data from 224 patients with steady-state trough concentrations (Css,trough) were analyzed. A parametric time-to-event (TTE) model was developed using NONMEM®, and the effects of treatments (SB8 and bevacizumab-EU) and patient demographic and clinical covariates on OS and PFS were evaluated. Simulations of median OS and PFS by bevacizumab Css,trough were conducted, and concentrations required to achieve 50% and 90% of the maximum median TTE were computed.Results: A log-logistics model with Css,trough best described the OS and PFS data. Treatment was not a predictor of the hazard for OS or PFS. Simulations revealed steep exposure–response curves with a phase of rapid rise before saturating to a plateau. The median Css,trough values of SB8 and bevacizumab-EU reported from the clinical study were on the plateaus of the exposure–response curves. The concentrations required to achieve 50% and 90% of the maximum effect were 82.4 and 92.2 μg/mL, respectively, for OS and 79.7 and 89.1 μg/mL, respectively, for PFS.Conclusion: Simulations based on the constructed TTE models for OS and PFS have well described the exposure–response relationship of bevacizumab in advanced NSCLC. The analysis demonstrated comparable efficacy between SB8 and bevacizumab-EU in terms of OS and PFS based on their exposure levels.

To explore the distribution and the resistance reaction of rice blast pathogens that may occur in North Korea, rice blast pathogens in the North Korean border regions of Dandong and Yeon-gil in China and the North Korean border region of Cheorwon in South Korea were analyzed. In addition, comparative analysis was con-ducted with rice blast pathogen in Suwon and Jeonju, inland regions of South Korea. Resistance reactions above average were observed in monogenic rice lines (IRBLzt-T, IRBL9-W, IRBL20-IR24, and IRBLta-CP1) in Jeonju, Suwon, and Cheorwon from 2018 to 2020. In Dandong and Yeon-gil, the monogenic lines IRBLz5-CA, IRBL12-M, and IRBL19-A consistently showed resistance reactions for three years. Notably, IRBL19-A exhibited strong resistance. Race distribution analysis in South Korea indicated a shift from KI to KJ dominance from 2018 to 2020, while in the North Korean border regions of Dandong and Yeon-gil, the KI race was dominant in 2021 and 2022. The race distribution of rice blast pathogens in China's North Korean border regions differed significantly from that in South Korea.

Abstract Background Under conditions of hypoxia, cancer cells with hypoxia inducible factor-1α (HIF-1α) from heterogeneous tumor cells show greater aggression and progression in an effort to compensate for harsh environmental conditions. Extensive study on the stability of HIF-1α under conditions of acute hypoxia in cancer progression has been conducted, however, understanding of its involvement during the chronic phase is limited. Methods In this study, we investigated the effect of SIRT1 on HIF1 stability in a typical chronic hypoxic conditon that maintains cells for 24 h under hypoxia using Western blotting, co-IP, measurement of intracellular NAD + and NADH levels, semi-quantitative RT-PCR analysis, invasion assay, gene knockdown. Results Here we demonstrated that the high concentration of pyruvate in the medium, which can be easily overlooked, has an effect on the stability of HIF-1α. We also demonstrated that NADH functions as a signal for conveyance of HIF-1α degradation via the SIRT1 and VHL signaling pathway under conditions of chronic hypoxia, which in turn leads to attenuation of hypoxically strengthened invasion and angiogenic activities. A steep increase in the level of NADH occurs during chronic hypoxia, leading to upregulation of acetylation and degradation of HIF-1α via inactivation of SIRT1. Of particular interest, p300-mediated acetylation at lysine 709 of HIF-1α is recogonized by VHL, which leads to degradation of HIF-1α via ubiquitin/proteasome machinary under conditions of chronic hypoxia. In addition, we demonstrated that NADH-elevation-induced acetylation and subsequent degradation of HIF-1α was independent of proline hydroxylation. Conclusions Our findings suggest a critical role of SIRT1 as a metabolic sensor in coordination of hypoxic status via regulation of HIF-1α stability. These results also demonstrate the involvement of VHL in degradation of HIF-1α through recognition of PHD-mediated hydroxylation in normoxia and p300-mediated HIF-1α acetylation in hypoxia.

Abstract EWS RNA binding protein 1 (EWSR1) is a multifunctional protein whose epigenetic signatures contribute to the pathogenesis of various human diseases, such as neurodegenerative disorders, skin development, and tumorigenic processes. However, the specific cellular functions and physiological characteristics of EWSR1 remain unclear. In this study, we used quantitative mass spectrometry-based proteomics with tandem mass tag labeling to investigate the global proteome changes in brain tissue in Ewsr1 knockout and wild-type mice. From 9115 identified proteins, we selected 118 differentially expressed proteins, which is common to three quantitative data processing strategies including only protein level normalizations and spectrum-protein level normalization. Bioinformatics analysis of these common differentially expressed proteins revealed that proteins up-regulated in Ewsr1 knockout mouse are mostly related to the positive regulation of bone remodeling and inflammatory response. The down-regulated proteins were associated with the regulation of neurotransmitter levels or amino acid metabolic processes. Collectively, these findings provide insight into the physiological function and pathogenesis of EWSR1 on protein level. Better understanding of EWSR1 and its protein interactions will advance the field of clinical research into neuronal disorders. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD026994.