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Abstract The rate of soil-transmitted helminth (STH) infection is estimated to be around 20% in Indonesia. Health promotion and health education are cost-effective strategies to supplement STH prevention and control programs. Existing studies suggest that quantitative tools for knowledge, attitudes and practices (KAP) are important to monitor effective community-based STH interventions. However, evidence is limited regarding the applicability of such tools. This study aims to identify the socio-demographic predictors for STH-related knowledge and practices and validate the quantitative tools in population use. A cross-sectional study design was conducted among residents of 16 villages in Central Java, Indonesia. Adult and child respondents were interviewed to assess general knowledge and practices in relation to STH. Two mixed effects models identified the significant factors in predicting knowledge and practice scores. The model predicted knowledge and practice scores were compared with the observed scores to validate the quantitative measurements developed in this study. Participants’ socio-demographic variables were significant in predicting an individual’s STH-related knowledge level and their hand washing and hygiene practices, taking into account household-level variability. Model validation results confirmed that the quantitative measurement tools were suitable for assessing STH associated knowledge and behaviour. The questionnaire developed in this study can be used to support school- and community-based health education interventions to maximize the effect of STH prevention and control programs.

The SUVmax is a measure of FDG uptake and is related with tumor aggressiveness in thyroid cancer, however, its association with molecular pathways is unclear. Here, we investigated the relationship between SUVmax and gene expression profiles in 80 papillary thyroid cancer (PTC) patients. We conducted an analysis of DEGs and enriched pathways in relation to SUVmax and tumor size. SUVmax showed a positive correlation with tumor size and correlated with glucose metabolic process. The genes that indicate thyroid differentiation, such as SLC5A5 and TPO, were negatively correlated with SUVmax. Unsupervised analysis revealed that SUVmax positively correlated with DNA replication(r = 0.29, p = 0.009), pyrimidine metabolism(r = 0.50, p

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality worldwide. Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that binds to programmed cell death-1 (PD-1), which is expressed in activated T cells and other immune cells and has been employed in cancer therapy, including HCC. Recently, PD-L1 overexpression has been documented in treatment-resistant cancer cells. Sorafenib is a multikinase inhibitor and the only FDA-approved treatment for advanced HCC. However, several patients exhibit resistance to sorafenib during treatment. This study aimed to assess the effect of glucose deprivation on PD-L1 expression in HCC cells. We used PD-L1-overexpressing HepG2 cells and IFN-γ-treated SK-Hep1 cells to explore the impact of glycolysis on PD-L1 expression. To validate the correlation between PD-L1 expression and glycolysis, we analyzed data from The Cancer Genome Atlas (TCGA) and used immunostaining for HCC tissue analysis. Furthermore, to modulate PD-L1 expression, we treated HepG2, SK-Hep1, and sorafenib-resistant SK-Hep1R cells with rapamycin. Here, we found that glucose deprivation reduced PD-L1 expression in HCC cells. Additionally, TCGA data and immunostaining analyses confirmed a positive correlation between the expression of hexokinase II (HK2), which plays a key role in glucose metabolism, and PD-L1. Notably, rapamycin treatment  decreased the expression of PD-L1 and HK2 in both high PD-L1-expressing HCC cells and sorafenib-resistant cells. Our results suggest that the modulation of PD-L1 expression by glucose deprivation may represent a strategy to overcome PD-L1 upregulation in patients with sorafenib-resistant HCC.

Despite advancements in cancer immunotherapy, solid tumors remain formidable challenges. In glioma, profound inter- and intra-tumoral heterogeneity of antigen landscape hampers therapeutic development. Therefore, it is critical to consider alternative sources to expand the repertoire of targetable (neo-)antigens and improve therapeutic outcomes. Accumulating evidence suggests that tumor-specific alternative splicing (AS) could be an untapped reservoir of antigens. In this study, we investigated tumor-specific AS events in glioma, focusing on those predicted to generate major histocompatibility complex (MHC)-presentation-independent, cell-surface antigens that could be targeted by antibodies and chimeric antigen receptor-T cells. We systematically analyzed bulk RNA-sequencing datasets comparing 429 tumor samples (from The Cancer Genome Atlas) and 9166 normal tissue samples (from the Genotype-Tissue Expression project), and identified 13 AS events in 7 genes predicted to be expressed in more than 10% of the patients, including PTPRZ1 and BCAN, which were corroborated by an external RNA-sequencing dataset. Subsequently, we validated our predictions and elucidated the complexity of the isoforms using full-length transcript amplicon sequencing on patient-derived glioblastoma cells. However, analyses of the RNA-sequencing datasets of spatially mapped and longitudinally collected clinical tumor samples unveiled remarkable spatiotemporal heterogeneity of the candidate AS events. Furthermore, proteomics analysis did not reveal any peptide spectra matching the putative antigens. Our investigation illustrated the diverse characteristics of the tumor-specific AS events and the challenges of antigen exploration due to their notable spatiotemporal heterogeneity and elusive nature at the protein levels. Redirecting future efforts toward intracellular, MHC-presented antigens could offer a more viable avenue.

The objective of this study was to evaluate the impact of dietary zinc supplementation in pre-weaned dairy calves on the phenotypic antimicrobial resistance (AMR) of fecal commensal bacteria. A repository of fecal specimens from a random sample of calves block-randomized into placebo (n = 39) and zinc sulfate (n = 28) groups collected over a zinc supplementation clinical trial at the onset of calf diarrhea, calf diarrheal cure, and the last day of 14 cumulative days of zinc or placebo treatment were analyzed. Antimicrobial susceptibility testing was conducted for Enterococcus spp. (n = 167) and E. coli (n = 44), with one representative isolate of each commensal bacteria tested per sample. Parametric survival interval regression models were constructed to evaluate the association between zinc treatment and phenotypic AMR, with exponentiated accelerated failure time (AFT) coefficients adapted for MIC instead of time representing the degree of change in AMR (MIC Ratio, MR). Findings from our study indicated that zinc supplementation did not significantly alter the MIC in Enterococcus spp. for 13 drugs: gentamicin, vancomycin, ciprofloxacin, erythromycin, penicillin, nitrofurantoin, linezolid, quinupristin/dalfopristin, tylosin tartrate, streptomycin, daptomycin, chloramphenicol, and tigecycline (MR = 0.96-2.94, p > 0.05). In E. coli, zinc supplementation was not associated with resistance to azithromycin (MR = 0.80, p > 0.05) and ceftriaxone (MR = 0.95, p > 0.05). However, a significant reduction in E. coli MIC values was observed for ciprofloxacin (MR = 0.17, 95% CI 0.03-0.97) and nalidixic acid (MR = 0.28, 95% CI 0.15-0.53) for zinc-treated compared to placebo-treated calves. Alongside predictions of MIC values generated from these 17 AFT models, findings from this study corroborate the influence of age and antimicrobial exposure on phenotypic AMR.

Abstract The neuropathology of mood disorders, including the diagnostic transition from major depressive disorder (MDD) to bipolar disorder (BD), is poorly understood. This study investigated resting-state electroencephalography (EEG) activity in patients with MDD and those whose diagnosis changed from MDD to BD. Among sixty-eight enrolled patients with MDD, the diagnosis of 17 patients converted to BD during the study period. We applied machine learning techniques to differentiate the two groups using sensor- and source-level EEG features. At the sensor level, patients with BD showed higher theta band power at the AF3 channel and low-alpha band power at the FC5 channel compared to patients with MDD. At the source level, patients with BD showed higher theta band activity in the right anterior cingulate and low-alpha band activity in the left parahippocampal gyrus. These four EEG features were selected for discriminating between BD and MDD with the best classification performance showing an accuracy of 80.88%, a sensitivity of 76.47%, and a specificity of 82.35%. Our findings revealed distinct theta and low-alpha band activities in patients with BD and MDD. These differences could potentially serve as candidate neuromarkers for the diagnosis and diagnostic transition between the two distinct mood disorders.

Abstract The relationship between obstructive sleep apnea (OSA) and chronic rhinosinusitis (CRS) has not yet been fully elucidated. Therefore, the objective of this study was to evaluate the connection between OSA risk and CRS by investigating associations between the STOP-Bang questionnaire and presence of CRS in a nationwide, population-based study. This is a cross-sectional study based on the Korean National Health and Nutrition Examination Survey (KNHANES). We evaluated 10,081 subjects who completed both the STOP-Bang and CRS-related questionnaires. Among the total subjects, 390 (3.9%) were CRS patients. The median STOP-Bang score was 3.0 [2.0; 4.0] in CRS patients, compared to 2.0 [1.0; 3.0] in subjects without CRS. In a low-risk group according to the STOP-Bang questionnaire, 3.1% of subjects were CRS patients. However, a gradual increase was observed among different risk groups. In the higher risk group, CRS patients accounted for 5.3% (P

Abstract Advances in next-generation sequencing technologies have led to elucidation of sensorineural hearing loss genetics and associated clinical impacts. However, studies on the functional pathogenicity of variants of uncertain significance (VUS), despite their close association with clinical phenotypes, are lacking. Here we identified compound heterozygous variants in ESRRB transcription factor gene linked to DFNB35, specifically a novel splicing variant (NM_004452.4(ESRRB): c.397 + 2T>G) in trans with a missense variant (NM_004452.4(ESRRB): c.1144C>T p.(Arg382Cys)) whose pathogenicity remains unclear. The splicing variant (c.397 + 2T>G) caused exon 4 skipping, leading to premature stop codon formation and nonsense-mediated decay. The p.(Arg382Cys) variant was classified as a VUS due to its particularly higher allele frequency among East Asian population despite disease-causing in-silico predictions. However, functional assays showed that p.(Arg382Cys) variant disrupted key intramolecular interactions, leading to protein instability. This variant also reduced transcriptional activity and altered expression of downstream target genes essential for inner ear function, suggesting genetic contribution to disease phenotype. This study expanded the phenotypic and genotypic spectrum of ESRRB in DFNB35 and revealed molecular mechanisms underlying ESRRB-associated DFNB35. These findings suggest that variants with high allele frequencies can also possess functional pathogenicity, providing a breakthrough for cases where VUS, previously unexplored, could be reinterpreted by elucidating their functional roles and disease-causing characteristics.

Abstract Because there is a lack of comparative studies assessing drug-coated balloon (DCB) and drug-eluting stent (DES) outcomes with respect to intraluminal (IL) and subintimal (SI) approaches in femoropopliteal (FP) total occlusive lesions, we compared the outcomes between DCB (including bailout stenting) and DES treatments for this lesion. A total of 487 limbs (434 patients) were divided into the IL (n = 344, DCB: n = 268, DES: n = 76) and SI (n = 143, DCB: n = 83, DES: n = 60) approach groups. The primary outcome was a major adverse limb event (MALE), defined as above-ankle amputation or repeat revascularization of the index limb. Secondary outcomes included clinically driven target lesion revascularization (TLR), loss of clinical patency, and all-cause death. After adjustment, in each IL and SI approach, the 2-year rates of MALE (p = 0.180 and p = 0.236, respectively), TLR, loss of clinical patency, and all-cause death were similar between the DCB and DES groups. In the DCB and DES groups, both primary and secondary outcomes were similar between the IL and SI approaches. DCB and DES strategies for patients presenting with FP total occlusive lesions demonstrated similar outcomes regardless of the IL or SI approach. Clinical Trial Registration: NCT02748226.

Abstract Cavities are characteristic radiological features related to increased mycobacterial burden and poor prognosis in Mycobacterium avium complex pulmonary disease (MAC-PD). However, cavity changes following treatment and their clinical implications remain unknown. We aimed to elucidate whether cavity obliteration or reduction in cavity size or wall thickness correlates with microbiological cure. In total, 136 adult patients with cavitary MAC-PD treated for ≥ 6 months between January 1st, 2009, and December 31st, 2021, in a tertiary referral centre in South Korea were enrolled. The cavity with the largest diameter at treatment initiation was tracked for size and thickness changes. Following median treatment of 20.0 months, 74 (54.4%) patients achieved microbiological cure. Cavity obliteration, achieved in 58 (42.6%) patients at treatment completion, was independently associated with microbiological cure. In patients with persistent cavities, size reduction of ≥ 10% was significantly associated with microbiological cure, whereas thickness reduction was not. Five-year mortality rates in patients with cavity obliteration, persistent but reduced cavity, and persistent cavity without shrinkage were 95.6%, 72.1%, and 65.3%, respectively (P

Abstract A structural adhesive series of biomass-based polyurethane (Biomass-PU) is synthesized using polypropylene glycol (PPG2000), isosorbide-based polyol (RPO300) as polyols, isophorone diisocyanate (IPDI) as an isocyanate and 4-tert-butylphenol (BP) as a capping agent. Three different equivalent ratios of PPG2000/RPO300, 9/1 (Biomass-PU1), 7/3 (Biomass-PU2), and 1/1 (Biomass-PU3), are evaluated to determine the effect of isosorbide-based polyol content on the properties and the optimizing formulation of biomass-PU structure adhesive. The 9/1 ratio of PPG2000/RPO300 substantially leads to the improvement of impact strength by up to 35 MPa, and the PPG2000/RPO300 = 9/1 ratio exhibits better thermal properties and impact strength than those of other ratios. To achieve more compatibility between biomass-PU structure adhesive and core–shell rubber (CSR) toughener, novel CSRs are successfully synthesized using acryl-PU as a shell and biomass-based PU as a core. The chemical structure of biomass-PU structure adhesives is analyzed through FT-IR Spectroscopy and NCO% titration. Thermal properties are evaluated using TGA and DSC analysis. Their molecular weights are measured by GPC. Also, the core–shell rubber (CSR) with a polyurethane shell is prepared to reinforce the impact strength of Biomass-PU structure adhesive.

Abstract Both the ε4 variant of the apolipoprotein E (APOE) gene and hearing loss are well-known risk factors for Alzheimer's disease. However, previous studies have produced inconsistent findings regarding the association between APOE genotypes and hearing levels, necessitating further investigation. The aim of this study was to investigate the relationship between APOE genotypes and hearing levels. This retrospective study analyzed clinical data from a clinical data warehouse of seven affiliated Catholic Medical Center hospitals. The study included 1,162 participants with records of APOE genotypes, audiometric tests, and cognitive function tests. In Generalized linear mixed model analysis, ε4 carriers exhibited lower pure tone audiometry thresholds with an estimate of -0.353 (SE = 0.126, p = 0.005). However, the interaction term for age and APOE ε4 had a coefficient of 0.577 (SE = 0.214 p = 0.006), suggesting that the APOE ε4 gene may accelerate hearing deterioration with age. Subgroup analysis based on an age cut-off of 75 revealed that ε4 carriers had better hearing at younger ages, but showed no significant difference at older ages. These results indicate that the ε4 allele may have a biphasic effect on hearing levels depending on age.

Abstract The Ames test is used worldwide to initially screen the mutagenic potential of new chemicals. In the standard Ames test, S. typhimurium strains (TA100, TA98, TA1535, and TA1537) and Escherichia coli (WP2uvrA) are treated with substances with/without cytochrome P450s (CYPs)-induced rat S9 fractions for identifying mutagens and pro-mutagens. However, many substances show completely different toxicity patterns depending on whether the liver S9 fraction belongs to rats or humans. The natural product Polygoni Multiflori Radix (PMR) can also show bacterial reverse mutation, followed by the rat or human liver S9 fraction. While PMR elicits reverse mutations in the TA1537 strain in rat liver S9 but not in human liver S9, this mechanism has not been verified yet. To explain this, the differences in metabolic enzymes compositions commonly observed between rats and humans have been implicated. This study aimed to explore the key factors that cause differences in the genotoxicity of PMR between rat and human liver S9 metabolic enzymes. The results of next-generation sequencing (NGS) analysis showed that both rat and human metabolic enzymes caused similar mutations in TA1537. However, when the metabolic enzymes in each S9 fraction were analyzed using ion mobility tandem mass spectrometry (IM-MS), rat- and human-specific enzymes were identified among the cytochrome (CYP) family, especially aryl hydrocarbon receptor (AHR)-related CYPs. These findings suggest that CYP1A1 isoforms contribute to the mechanism of PMR in the Ames test. Therefore, an in vitro Ames test might be more reliable in predicting genotoxicity for both rodents and humans. This will also help overcome the limitations of laboratory animal-based toxicity evaluations, which provide unreliable results due to interspecies differences between humans and rodents.

Abstract Immune checkpoint blockades are actively adopted in diverse cancer types including metastatic melanoma and lung cancer. Despite of durable response in 20–30% of patients, we still lack molecular markers that could predict the patient responses reliably before treatment. Here we present a composite model for predicting anti-PD-1 response based on tumor mutation burden (TMB) and transcriptome sequencing data of 85 lung adenocarcinoma (LUAD) patients who received anti-PD-(L)1 treatment. We found that TMB was a good predictor (AUC = 0.81) for PD-L1 negative patients (n = 20). For PD-L1 positive patients (n = 65), we built an ensemble model of 100 XGBoost learning machines where gene expression, gene set activities and cell type composition were used as input features. The transcriptome-based models showed excellent accuracy (AUC > 0.9) and highlighted the contribution of T cell activities. Importantly, nonresponder patients with high prediction score turned out to have high CTLA4 expression, which suggested that neoadjuvant CTLA4 combination therapy might be effective for these patients. Our data and analysis results provide valuable insights into developing biomarkers and strategies for treating LUAD patients using immune checkpoint inhibitors.

Abstract This study investigated whether hospital factors, including patient volume, unit level, and neonatologist staffing, were associated with variations in standardized mortality ratios (SMR) adjusted for patient factors in very-low-birth-weight infants (VLBWIs). A total of 15,766 VLBWIs born in 63 hospitals between 2013 and 2020 were analyzed using data from the Korean Neonatal Network cohort. SMRs were evaluated after adjusting for patient factors. High and low SMR groups were defined as hospitals outside the 95% confidence limits on the SMR funnel plot. The mortality rate of VLBWIs was 12.7%. The average case-mix SMR was 1.1; calculated by adjusting for six significant patient factors: antenatal steroid, gestational age, birth weight, sex, 5-min Apgar score, and congenital anomalies. Hospital factors of the low SMR group (N = 10) had higher unit levels, more annual volumes of VLBWIs, more number of neonatologists, and fewer neonatal intensive care beds per neonatologist than the high SMR group (N = 13). Multi-level risk adjustment revealed that only the number of neonatologists showed a significant fixed-effect on mortality besides fixed patient risk effect and a random hospital effect. Adjusting for the number of neonatologists decreased the variance partition coefficient and random-effects variance between hospitals by 11.36%. The number of neonatologists was independently associated with center-to-center differences in VLBWI mortality in Korea after adjustment for patient risks and hospital factors.

Abstract The E-Health Big Data Evidence Innovation Network (FeederNet) in Korea, based on the observational medical outcomes partnership (OMOP) common data model (CDM), had 72.3% participation from tertiary hospitals handling severe diseases as of October 2022. While this contributes to the activation of multi-institutional research, concerns about the comprehensiveness of device data persist due to the adoption of national health insurance corporation (NHIC) claim codes as device identifiers in the medical device field. This study critically evaluated the effectiveness and compatibility of NHIC claim codes and unique device identifier (UDI) within FeederNet to identify the optimal identifier for efficient Post-market surveillance (PMS). Specifically, this study addressed three main questions: (1) the number of UDIs classified as NHIC-covered items, (2) the number of UDIs included in each NHIC claim code, and (3) the number of NHIC claim codes each UDI covers. Among the 1,979,655 UDIs registered domestically, only 36.02% (712,983) were classified as covered by National Health Insurance. NHIC-covered medical devices were limited to categories (A) medical devices, (B) medical supplies, and (C) dental materials, excluding most software and in vitro diagnostics (IVD). Multiple UDIs could be registered under a single NHIC claim code, and a single UDI could be registered under multiple NHIC claim codes. Only 32.62% (13,756/42,171) of NHIC claim codes had registered UDIs, with an average of 53 UDIs per claim code. Of the UDIs listed as NHIC covered, 92.39% (659,046/713,341) had one claim code, while 7.25% (51,652) had multiple claim codes. Additionally, 2643 UDIs were listed as NHIC covered but had no registered claim codes. Due to this complex relationship, NHIC claim code-based PMS may pool safe and unsafe models or disperse problematic models across multiple claim codes, leading to a lower problem rate or insignificant differences between claim codes, thus reducing signal detection sensitivity compared to UDI-based PMS. In conclusion, NHIC claim code-based PMS has limitations in granularity and signal detection sensitivity, necessitating the adoption of UDI-based PMS to address these issues. The UDI system can enhance the accuracy of medical device identification and tracking, playing a crucial role in generating real-world evidence (RWE) by integrating data from various sources. Future research should explore specific strategies for integrating and utilizing UDI with NHIC claim codes, contributing to the implementation of a more reliable and comprehensive PMS in Korea’s healthcare system.

Abstract Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne illness with a notable morality risk that is becoming increasingly prevalent in East Asia (14–36%). Increasing evidence indicates a more direct role of the SFTS virus in renal impairment. However, few studies have explored the risk factors for and clinical outcomes of AKI in patients with SFTS. Therefore, in this study, we aimed to investigate risk factors and outcomes associated with AKI in patients with SFTS. In this retrospective cohort study, we included the data of 53 patients who were diagnosed with SFTS virus infection at Kangwon National University Hospital between 2016 and 2020. We incorporated laboratory data and medical information including comorbidities, complications, and mortality. Baseline characteristics, clinical features, laboratory parameters, and mortality rates of the non-AKI and AKI groups were compared. Patient survival of non-AKI and AKI groups were compared using the Kaplan–Meier method. To identify the population with poor prognosis, Cox regression analysis was used to identify the independent risk factors for in-hospital mortality in patients with SFTS. Of the 53 individuals, 29 (54.7%) were male, with an average age of 66.5 years. Nine patients (15.1%) died of SFTS. Twenty-seven (50.9%) patients exhibited AKI; the average time interval from fever onset to AKI occurrence was 3.6 days. Notably, 24 (88.9%) patients developed AKI within the first week of fever onset. Patients in the AKI group exhibited a significantly higher prevalence of diabetes and were older than those in the non-AKI group. The mortality rate was notably higher (29.6%) in the AKI group than in the non-AKI group (3.8%). Within the AKI cohort, advanced stages (stages 2 and 3) showed a 50% mortality rate, which was significantly higher than the 17.6% mortality rate in patients with stage 1 AKI. Additionally, Kaplan–Meier curves revealed lower survival rates among patients with AKI than among those without AKI (P = 0.017). Cox regression analysis identified leukopenia and elevated serum creatinine levels as significant risk factors for mortality. AKI is a common complication associated with SFTS. Moreover, the mortality rate was significantly higher in the patients who developed AKI than in those who did not. Our findings underscore the pivotal role of AKI as a prognostic marker of disease severity in patients with SFTS.

Abstract Among patients with epilepsy, 30–40% experience recurrent seizures even after adequate antiseizure medications therapies, making them refractory. The early identification of refractory epilepsy is important to provide timely surgical treatment for these patients. In this study, we analyze interictal electroencephalography (EEG) data to predict drug refractoriness in patients with temporal lobe epilepsy (TLE) who were treated with monotherapy at the time of the first EEG acquisition. Various EEG features were extracted, including statistical measurements and interchannel coherence. Feature selection was performed to identify the optimal features, and classification was conducted using different classifiers. Functional connectivity and graph theory measurements were calculated to identify characteristics of refractory TLE. Among the 48 participants, 34 (70.8%) were responsive, while 14 (29.2%) were refractory over a mean follow-up duration of 38.5 months. Coherence feature within the gamma frequency band exhibited the most favorable performance. The light gradient boosting model, employing the mutual information filter-based feature selection method, demonstrated the highest performance (AUROC = 0.821). Compared to the responsive group, interchannel coherence displayed higher values in the refractory group. Interestingly, graph theory measurements using EEG coherence exhibited higher values in the refractory group than in the responsive group. Our study has demonstrated a promising method for the early identification of refractory TLE utilizing machine learning algorithms.

Abstract Failure rate after chronic rotator cuff repair is considerably high. Moreover, diabetes mellitus is known as a compromising factor of rotator cuff tear. The effect of Polydeoxyribonucleotide (PDRN) and polynucleotide (PN) on tendon healing and fatty infiltration is unclear as tissue regeneration activator in diabetic state. Therefore, a diabetic rat model with chronic rotator cuff tear was made for mechanical, histologic and blood tests. In the animal study using a diabetic rat cuff repair model, the administration of PDRN and PN increased the load to failure of repaired cuffs and improved tendon healing and decreased fatty infiltration. Also, the plasma levels of vascular endothelial growth factor and fibroblast growth factor were elevated in PDRN and PN administrated groups. We concluded that PDRN and PN appear to boost tendon recovery and reduce the presence of fatty infiltration following cuff repair in diabetic state. Also, PN showed a later onset and a longer duration than PDRN associated with the mean plasma growth factors.

Abstract A germinal disc located on the egg yolk surface drives genetic modification. Windowed and surrogate eggshell incubation methods have been developed, but these exhibit limited abilities to generate transgenic chickens. In the present study, we investigated the frequency of observing the germinal disc according to the preincubation positioning direction and time and found that it depended on those conditions, but only a few chicks (2.8–5.6%) hatched using the windowed method. Then, we attempted to improve surrogate method via one- or two-step procedures. All eggs, including surrogates that were 10 g heavier than the donor eggs, were obtained from a poultry flock of the same age. With the one-step surrogate method, where the donor egg was transferred only once through a 3.5 cm hole on the point end, at the first day of preincubation, into the surrogate egg, the survival rate at day 4 was 30.8%, and the hatching rate was 11.8%. With the two-step surrogate method (transfer was on the 1st and 4th day of incubation), the survival rate at day 4 was improved to 90.7%, and a hatching rate of 70.0% was achieved. Therefore, this method can be effective for in ovo artificial incubation.

Abstract High-energy impacts, like vehicle crashes or falls, can lead to pelvic ring injuries. Rapid diagnosis and treatment are crucial due to the risks of severe bleeding and organ damage. Pelvic radiography promptly assesses fracture extent and location, but struggles to diagnose bleeding. The AO/OTA classification system grades pelvic instability, but its complexity limits its use in emergency settings. This study develops and evaluates a deep learning algorithm to classify pelvic fractures on radiographs per the AO/OTA system. Pelvic radiographs of 773 patients with pelvic fractures and 167 patients without pelvic fractures were retrospectively analyzed at a single center. Pelvic fractures were classified into types A, B, and C using medical records categorized by an orthopedic surgeon according to the AO/OTA classification system. Accuracy, Dice Similarity Coefficient (DSC), and F1 score were measured to evaluate the diagnostic performance of the deep learning algorithms. The segmentation model showed high performance with 0.98 accuracy and 0.96–0.97 DSC. The AO/OTA classification model demonstrated effective performance with a 0.47–0.80 F1 score and 0.69–0.88 accuracy. Additionally, the classification model had a macro average of 0.77–0.94. Performance evaluation of the models showed relatively favorable results, which can aid in early classification of pelvic fractures.

Abstract Non-small cell lung cancer (NSCLC) remains a significant challenge, as it is one of the leading causes of cancer-related deaths, and the development of resistance to anticancer therapy makes it difficult to treat. In this study, we investigated the anticancer mechanism of deoxybouvardin (DB), a cyclic hexapeptide, in gefitinib (GEF)-sensitive and -resistant NSCLC HCC827 cells. DB inhibited the viability and growth of HCC827 cells in a concentration- and time-dependent manner. In vitro kinase assay showed DB inhibited epidermal growth factor receptor (EGFR), mesenchymal–epithelial transition (MET), and AKT, and their phosphorylation was suppressed in HCC827 cells treated with DB. A molecular docking model suggested that DB interacts with these kinases in the ATP-binding pockets. DB induces ROS generation and cell cycle arrest. DB treatment of HCC827 cells leads to mitochondrial membrane depolarization. The induction of apoptosis through caspase activation was confirmed by Z-VAD-FMK treatment. Taken together, DB inhibited the growth of both GEF-sensitive and GEF-resistant NSCLC cells by targeting EGFR, MET, and AKT and inducing ROS generation and caspase activation. Further studies on DB can improve the treatment of chemotherapy-resistant NSCLC through the development of effective DB-based anticancer agents.

Abstract Subjects who have ischemia with non-obstructive coronary arteries (INOCA) experience angina pectoris with evidence of myocardial ischemia but without coronary stenosis. Few studies have investigated factors associated with its survival, especially insulin resistance. In this study, subjects with angina pectoris, without known diabetes mellites (DM), and with non-invasive tests showing myocardial ischemia were admitted for coronary angiography (CAG). Those whose CAG did not reveal stenosis and agreed to receive an oral glucose tolerance test (OGTT) 2 weeks after hospital discharge were enrolled for analysis. All-cause mortality was recorded, which served as the outcome of the study. A total of 587 subjects with INOCA, without known DM, and with OGTT data were analyzed. After OGTT and HbA1c tests, 86 subjects (14.7%) were newly diagnosed with DM and 59.8% had pre-DM. The median duration of follow-up was 7.03 years. Thirty-nine subjects died during the follow-up period. The incidence rate of mortality was 9.9 /1000 person-year. Those who died had a higher fasting glucose (101 ± 17 vs. 94 ± 13 mg/dl, p = 0.003) but a lower estimated glomerular filtration rate (eGFR) (54 ± 22 vs. 87 ± 30 ml/min, p

Abstract Glioblastoma multiforme (GBM) is the most aggressive type of cancer in the brain and has an inferior prognosis because of the lack of suitable medicine, largely due to its tremendous invasion. GBM has selfish metabolic pathways to promote migration, invasion, and proliferation compared to normal cells. Among various metabolic pathways, NAD (nicotinamide adenine dinucleotide) is essential in generating ATP and is used as a resource for cancer cells. LbNOX (Lactobacillus brevis NADH oxidase) is an enzyme that can directly manipulate the NAD+/NADH ratio. In this study, we found that an increased NAD+/NADH ratio by LbNOX or mitoLbNOX reduced intracellular glutamate and calcium responses and reduced invasion capacity in GBM. However, the invasion was not affected in GBM by rotenone, an ETC (Electron Transport Chain) complex I inhibitor, or nicotinamide riboside, a NAD+ precursor, suggesting that the crucial factor is the NAD+/NADH ratio rather than the absolute quantity of ATP or NAD+ for the invasion of GBM. To develop a more accurate and effective GBM treatment, our findings highlight the importance of developing a new medicine that targets the regulation of the NAD+/NADH ratio, given the current lack of effective treatment options for this brain cancer.

Abstract It has been reported that a scenario-based cognitive behavioral therapy mobile app including Todac Todac was effective in improving depression in the general public. However, no study has been conducted on whether Todac Todac is effective in dialysis patients. Therefore, this study was intended to determine whether the use of this app was effective in improving depression in dialysis patients. Sixty-five end-stage kidney disease patients receiving dialysis at Soonchunhyang University Cheonan Hospital were randomly assigned to the Todac Todac app program (experimental group) or an E-moods daily mood chart app program (control group) for 3 weeks. The degree of depression was measured before and after using the app.After the end of the 3-week program, a small but significant improvement was observed in the Trait anxiety (p

Abstract The relative frequency of primary cutaneous lymphoma (PCL) subtypes shows wide variation across different geographical regions. This retrospective study was conducted in a tertiary referral center located in Korea to describe the relative frequency, demographics, survival outcomes, and temporal trend in PCL. A total of 627 PCL cases diagnosed between January 1994 and December 2022 were included. The majority of PCL cases (87.2%) were of T-/NK-cell lineage (CTCL), while the remaining cases (12.8%) were B-cell lineage lymphomas (CBCL). The prevalence of mycosis fungoides (MF) in CTCL increased significantly over time, while other CTCL subtypes, including primary cutaneous extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), decreased in frequency. Notably, the prevalence of CD4-positive small/medium T-cell lymphoproliferative disorder showed a substantial increase over time. Primary cutaneous marginal zone lymphoma was consistently the commonest CBCL subtype. Survival analysis demonstrated that CTCL had a more favorable 5-year overall survival (OS) than CBCL. OS rate of MF, SPTCL, and primary cutaneous peripheral T-cell lymphoma, NOS improved significantly over time. This study provides comprehensive insights into the dynamic change in the relative frequency and overall survival of PCL subtypes over time.

Abstract No study has analysed the temporal trends of the long-term results and clinical characteristics of patients with hepatocellular carcinoma (HCC) treated using radiofrequency ablation (RFA). Therefore, we examined temporal trends of characteristics of patients and treatment-naïve HCCs within the Milan criteria treated by RFA over 20 years. We retrospectively analysed 1099 patients with HCC within the Milan criteria treated with percutaneous RFA from January 2000 to December 2019. The overall survival (OS), recurrence-free survival (RFS), and factors affecting survival and local tumor progression were analysed using the Kaplan‒Meier method and Cox proportional hazards model. A trend test was performed to analyse the changing trends in participants and treatment outcomes. The overall and RFS of patients improved during the later period. In addition, viral hepatitis-related HCC incidence decreased, whereas that of alcohol- or non-alcoholic fatty liver disease-related HCC increased from the earlier to the later period (P for trend

Abstract Titrating tacrolimus concentration in liver transplantation recipients remains a challenge in the early post-transplant period. This multicenter retrospective cohort study aimed to develop and validate a machine-learning algorithm to predict tacrolimus concentration. Data from 443 patients undergoing liver transplantation between 2017 and 2020 at an academic hospital in South Korea were collected to train machine-learning models. Long short-term memory (LSTM) and gradient-boosted regression tree (GBRT) models were developed using time-series doses and concentrations of tacrolimus with covariates of age, sex, weight, height, liver enzymes, total bilirubin, international normalized ratio, albumin, serum creatinine, and hematocrit. We conducted performance comparisons with linear regression and populational pharmacokinetic models, followed by external validation using the eICU Collaborative Research Database collected in the United States between 2014 and 2015. In the external validation, the LSTM outperformed the GBRT, linear regression, and populational pharmacokinetic models with median performance error (8.8%, 25.3%, 13.9%, and − 11.4%, respectively; P

Abstract The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient’s primary and/or metastatic tumor. An in-house developed assay (UHS assay) was employed for a tumor-informed ctDNA assay during treatment and follow-up. A median of three (range 1–5) anchor mutations per case were applied for ctDNA detection. ctDNA was detected in 14 (63.6%, 14/22) cases at the time of enrollment and 18 (78.5%, 18/23) cases during follow-up. More anchor mutations and higher tumor burden were significantly related to higher ctDNA positive rates (p-value 0.036, 0.043, respectively). The mean enriched variant allele frequency (eVAF) at each time point was significantly higher for stable or progressive disease responses (ANOVA test p-value

Abstract This study aimed to establish a deep learning-based predictive model for the prognosis of idiopathic sudden sensorineural hearing loss (SSNHL). Data from 1108 patients with SSNHL between January 2015 and May 2023 were retrospectively analyzed. Patients underwent standardized treatment protocols including high-dose steroid therapy and hearing outcomes were assessed after three months using Siegel’s criteria and the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) classification. For predicting patient recovery, a two-layered classification process was implemented. Initially, a set of 22 Multilayer Perceptrons (MLP) networks was employed to categorize the patients. The outcomes from this initial categorization were subsequently relayed to a second-layer meta-classifier for final prognosis determination. The validity of this methodology was ascertained through a K-fold cross-validation procedure executed with 10 distinct splits. The prediction model for complete recovery, based on Siegel’s criteria, demonstrated an accuracy of 0.892 and area under the curve (AUC) of 0.922. For the class A prediction, according to AAO-HNS classification, the model showed an accuracy of 0.847 and AUC of 0.918. These results suggest that the model may have the potential to contribute to the establishment of tailored patient management strategies by predicting hearing recovery in patients with SSNHL.

Abstract This study evaluated the positive predictive value (PPV) of artificial intelligence (AI) in detecting pneumothorax on chest radiographs (CXRs) and its affecting factors. Patients determined to have pneumothorax on CXR by a commercial AI software from March to December 2021 were included retrospectively. The PPV was evaluated according to the true-positive (TP) and false-positive (FP) diagnosis determined by radiologists. To know the factors that might influence the results, logistic regression with generalized estimating equation was used. Among a total of 87,658 CXRs, 308 CXRs with 331 pneumothoraces from 283 patients were finally included. The overall PPV of AI about pneumothorax was 41.1% (TF:FP = 136:195). The PA view (odds ratio [OR], 29.837; 95% confidence interval [CI], 15.062–59.107), high abnormality score (OR, 1.081; 95% CI, 1.066–1.097), large amount of pneumothorax (OR, 1.005; 95% CI, 1.003–1.007), presence of ipsilateral atelectasis (OR, 3.508; 95% CI, 1.509–8.156) and a small amount of ipsilateral pleural effusion (OR, 5.277; 95% CI, 2.55–10.919) had significant effects on the increasing PPV. Therefore, PPV for pneumothorax diagnosis using AI can vary based on patients’ factors, image-acquisition protocols, and the presence of concurrent lesions on CXR.

Abstract Cuticle quality can affect food safety by protecting poultry eggs from bacterial infection in the modern poultry industry. However, genetic factors related to cuticle nanostructure are not much reported due to limited bird models. In the current study, the genome-edited quail targeting myostatin (MSTN) gene was used to investigate the effect of MSTN mutation on the cuticle nanostructure and quality. To analyze nanostructure of the cuticle layer of the MSTN mutant and wild-type (WT) quail eggs, scanning electron microscope (SEM) images was taken. Thickness of the cuticle layer did not differ between the MSTN mutant and WT groups, but the size of the nanospheres in the surface of the cuticle layer was increased by MSTN mutation. In addition, increased size of the nanospheres in the MSTN mutant group was also shown in the upper region of the cross-sectional cuticle layer. Notably, both groups showed similar small-sized nanospheres in the lower region of the cuticle layer and the size was increased as they ascended to the upper region. The data suggested that MSTN mutation increased the size of the nanosphere in the upper region of the cuticle layer at a late phase rather than increasing the size of nanospheres in the lower region of the cuticle layer at an early phase of cuticle formation. However, the number of Escherichia coli attached to the surface did not differ between the two groups indicating no association between nanosphere size and bacterial attachment in quail eggs. The current study demonstrated a new function of the MSTN gene on regulation of cuticle nanostructure, for the first time. These results advanced our knowledge on the association between genetic factors and cuticle nanostructure and can be served as a reference to study the mechanism of cuticle formation in the future study.

Abstract Non-alcoholic fatty liver disease (NAFLD) is a relatively common disease, and preventing its occurrence is important for both individual health and reducing social costs. Shift work is reported to have several negative effects on health. An association has been observed between NAFLD and both sleep time and quality; however, this association remains unclear in night shift workers. We aimed to evaluate the relationship between shift work and the incidence of NAFLD. Overall, 45,149 Korean workers without NAFLD were included at baseline. NAFLD was defined as the presence of a fatty liver observed on ultrasonography without excessive alcohol use. incidence rate ratios for incident NAFLD were estimated using negative binomial regression according to age groups (20s, 30s, 40s, and 50s). In the 20s age group, shift work showed a significant incidence rate ratio (IRR) for NAFLD in all models. After adjusting for all variables, the IRR (95% confidence interval) was 1.24 (1.08–1.43) in the 20s age group. In their 20s, a significant association between shift work and incident NAFLD was consistently observed among women and workers with poor sleep quality. In this large-scale cohort study, shift work was significantly associated with the development of NAFLD among young workers in their 20s.

Abstract Inflammatory bowel disease is defined by inflammation and immune dysregulation. This study investigated the effects of Gα13 liver-specific knockout (LKO) on proximal and distal colons of dextran sodium sulfate (DSS)-induced mice in conjunction with a high-fat diet (HFD). HFD improved body weight gain and disease activity index scores. Gα13LKO exerted no improvement. In the proximal colon, HFD augmented the DSS effect on Il6, which was not observed in Gα13LKO mice. In the distal colon, HFD plus DSS oppositely fortified an increase in Tnfa and Cxcl10 mRNA in Gα13LKO but not WT. Il6 levels remained unchanged. Bioinformatic approaches using Gα13LKO livers displayed bile acid and cholesterol metabolism-related gene sets. Cholic acid and chenodeoxycholic acid levels were increased in the liver of mice treated with DSS, which was reversed by Gα13LKO. Notably, mice treated with DSS showed a reduction in hepatic ABCB11, CYP7B1, CYP7A1, and CYP8B1, which was reversed by Gα13LKO. Overall, feeding HFD augments the effect of DSS on Il6 in the proximal colon of WT, but not Gα13LKO mice, and enhances DSS effect on Tnfa and Cxcl10 in the distal colon of Gα13LKO mice, suggesting site-specific changes in the inflammatory cytokines, potentially resulting from changes in BA synthesis and excretion.

Abstract REBa $$_2$$ 2 Cu $$_3$$ 3 O $$_{7-\text {x}}$$ 7 - x (REBCO, RE = rare earth)-coated conductor is a competitive option in terms of current-carrying capacity and high-stress durability in developing high-field magnets for nuclear magnetic resonance (NMR) research. Meanwhile, a technical challenge in utilizing a stand-alone REBCO NMR magnet is an unexpected difference in the field uniformity between the designed and measured values after being constructed and charged, i.e., harmonic errors. Bortot et al., and Li et al., reported analytic evidence of the related issue. However, sufficient research has not yet been conducted, so evidence should be supplemented further. Here we report harmonic errors due to screening current and inconsistent conductor thickness, confirmed by a 400 MHz 1H NMR magnet development project. The magnet was first charged up to its operating current, and then multiple overcharge-discharge cycles were applied, which was an empirically optimized operation protocol. A field mapping device obtained magnetic fields at designated locations in the room-temperature bore. The result showed over 100 ppm field uniformity difference between designed and measured values. A simulation model was developed considering screening current and inconsistent conductor thickness for reproducing the field distribution. Comparison of voltages and fields between simulation and measurement validated the model. Further analysis of the overcharge-discharge effect on harmonic errors demonstrated that even and odd-order harmonics are mainly attributed to screening current and geometric inconsistency while confirming the limitation of the screening current mitigation effect. Hence, we concluded that the desirable requirement of the sub-ppm level field uniformity generation might be barely possible with the current REBCO NMR magnet design approach.

Abstract In recent years, finite element analysis (FEA) has been instrumental in comparing the biomechanical stability of various implants for femur fracture treatment and in studying the advantages and disadvantages of different surgical techniques. This analysis has proven helpful for enhancing clinical treatment outcomes. Therefore, this study aimed to numerically analyze fixed stability according to location using FEA. In this study, a virtual finite element model was created based on a clinically anatomically reduced patient. It incorporated positive and negative support derived from intramedullary and extramedullary reduction from the anteroposterior (AP) view and neutral support from the lateral view. The generated model was analyzed to understand the biomechanical behavior occurring in each region under applied physiological loads. The simulation results of this study showed that the average von Mises stress (AVMS) of the nail when performing intramedullary reduction for femoral fixation was 187% of the anatomical reduction and 171% of the extramedullary reduction, and individually up to 2.5 times higher. In other words, intramedullary reduction had a very high possibility of fixation failure compared to other reduction methods. This risk is amplified significantly, especially in situations where bone strength is compromised due to factors such as old age or osteoporosis, which substantially affects the stability of fixation. Extramedullary reduction, when appropriately positioned, demonstrates greater stability than anatomical reduction. It exhibits stable fixation even in scenarios with diminished bone strength. In instances in which the bone density was low in the support position, as observed in the lateral view, the AVMS on the nail appeared to be relatively low, particularly in cases of positive support. Additionally, the femur experienced lower equivalent stress only in the extramedullary reduction-negative position. Moreover, by comparing different reduction methods and bone stiffness values using the same femoral shape, this study offers insights into the selection of appropriate reduction methods. These insights could significantly inform decision making regarding surgical strategies for intertrochanteric fractures.

Abstract The prognostic value of central pathology review in upper urinary tract cancer (UTUC) remains inadequately addressed in existing literature. In this study, we conducted an extensive central pathology review and presented its influence on multi-center UTUC studies. We conducted a retrospective review of patients who underwent radical nephroureterectomy or segmental resection for UTUC to determine eligibility for central pathology review. In the Taiwan UTUC Collaboration cohort, 377 cases met the criteria for pathology review. We assessed agreement between pathologists using both the total percentage of agreement and simple kappa statistics. The prognostic implications of original and review pathology for various parameters were examined using the Cox regression model. This study included 209 female and 168 male participants. Pathology review revealed substantial interobserver variability in pT staging, with a particularly high rate of pT2 cases being upgraded to pT3 upon central review (17/70 pT2 stage made by local pathologists were finally confirmed as pT3 disease by the review pathologist). The local pathologist cohort identified fewer significant histological predictors in survival models compared to the review pathology cohort. Advanced pT stage, perineural invasion (PNI), and positive surgical margin were independent predictors of poorer overall survival and cancer-specific survival. PNI, lymphatic vascular invasion, and positive surgical margin were independent predictors of disease recurrence. Substantial interobserver variability in histological assessment underscores the importance of centralized pathology review for both multi-center studies and accurate post-operative management of UTUC patients. Advanced stage, perineural invasion, and margin status were significant histological predictors of oncological outcomes.

Abstract Ticks are blood-sucking ectoparasites that act as vectors for transmission of various pathogens. The purpose of this study was to assess tick-borne bacteria, whether pathogenic or not, in ticks distributed in Korea using 16S rRNA metabarcoding and to confirm the results by PCR. Questing ticks were collected from four provinces in Korea in 2021 using the flagging method. After pooling the DNAs from the 61 tick pools (including 372 ticks), the bacterial 16S rRNA V3–V4 hypervariable region was amplified and sequenced using the MiSeq platform. Rickettsia, Ehrlichia, and the endosymbiont Wolbachia were confirmed by conventional PCR and molecular analysis. In total, 6907 ticks (534 pools) were collected and identified as belonging to five species (Haemaphysalis spp., H. longicornis, H. flava, I. nipponensis, and A. testudinarium). Through 16S rRNA metabarcoding, 240 amplicon sequence variants were identified. The dominant taxa were Rickettsiella and Coxiella. Additionally, pathogenic bacteria such as Rickettsia and Ehrlichia, endosymbiotic bacteria such as Wolbachia and Spiroplasma were identified. Polymerase chain reaction (PCR) was performed to confirm the presence of Rickettsia, Ehrlichia, Bartonella, and Wolbachia in individual ticks. Overall, 352 (65.92%) of 534 pools tested positive for at least one of the screened tick-borne bacteria. Rickettsia was the most prevalent (61.42%), followed by Wolbachia (5.05%). Ehrlichia was detected in 4.86% of tested samples, whereas Bartonella was not detected. In this study, 16S rRNA metabarcoding revealed the presence of Rickettsia, Wolbachia, and Ehrlichia, in that order of abundance, while showing absence of Bartonella. These results were confirmed to exhibit the same trend as that of the conventional PCR. Therefore, large-scale screening studies based on pooling, as applied in this study, will be useful for examining novel or rare pathogens present in various hosts and vectors.

Abstract Parents adjust their foraging effort according to the chick and their own body condition and dual foraging strategy is one of the foraging tactics parents replenish their own reserves while feeding their chicks. During the post-breeding season, seabirds disperse to recover their own body condition and prepare for the next breeding season. Recently, we discovered Black-tailed gulls (Larus crassirostris) breeding around the Korean Peninsula occasionally foraging long trips during the late fledging, however, our understanding of the behavioral patterns of Black-tailed gulls during the late fledging and post-breeding, as well as its inter-colonial differences, remains considerably limited. Here, we employed 92 GPS trackers to adult Black-tailed gulls (Larus crassirostris) from six breeding colonies around the Korean peninsula (Yellow Sea—three colonies, South Sea—one colony, and East Sea—two colonies). To determine the foraging investment during the fledging, we suggested the flight efficiency in each trip as the ratio of maximum foraging distance (i.e., straight line distance) to total foraging distance (i.e., sum of all consecutive distance for each trip). Overall, the mean flight efficiency of the long foraging trips were lower than 57% (40.76 ± 13.07%) whereas that of the short foraging trips were over 74% (80.87 ± 4.03%). This may suggest that Black-tailed gulls may visited more than one foraging site during the long foraging trip while they flew directly between the foraging site and breeding colony during the short foraging trip to invest more in their juvenile. Moreover, longer maximum foraging distance with higher flight efficiency observed in the East Sea may indicate a balance between the costs (such as energy expended during foraging or food competition near breeding sites) and the benefits (quantity and quality of food obtained). Our findings revealed the flight behavior of Black-tailed gulls during the late fledging and post breeding, across six breeding colonies, which have different competition pressures and proximity to foraging site.

Abstract Tylosin, an antibiotic with a long history in treating respiratory bacterial infections, has unknown effects on the gut microbiota of healthy and infected pigs. The study aimed to investigate the effect of a therapeutic dose of tylosin on swine gut microbiota and explored the relationship between this effect and tylosin pharmacokinetics (PK). We also assessed whether changes in gut microbiota after tylosin administration differ between healthy animals (n = 7) and animals intranasally co-infected (n = 7) with Actinobacillus pleuropneumoniae and Pasteurella multocida. Both groups were intramuscularly administered with tylosin (20 mg/kg). The 16S rRNA gene analyses revealed a significantly lower species richness and diversity, after tylosin treatment, in the infected than the healthy pigs, with infected pigs having lower levels of Bacteroidetes and Firmicutes and higher levels of Proteobacteria. Greater tylosin exposure (greater area under curve (AUC) and maximum plasma concentration (Cmax), and slower elimination (longer terminal half-life, T1/2) were observed in healthy than infected pigs. Relative abundance of Lactobacillus, Oscillibacter, Prevotella, and Sporobacter was positively and significantly correlated with AUC and Cmax, whereas the abundance of Acinetobacter, Alishewanella, and Pseudomonas was positively and significantly correlated with T1/2 and mean residence time (MRT) of tylosin. Our findings, for the first time, demonstrated significant changes in swine gut microbiota after a single therapeutic dose of tylosin was administered, whereas the effect of these changes on tylosin PK was not evident.

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

Abstract Patients with mental illnesses, particularly psychosis and obsessive‒compulsive disorder (OCD), frequently exhibit deficits in executive function and visuospatial memory. Traditional assessments, such as the Rey‒Osterrieth Complex Figure Test (RCFT), performed in clinical settings require time and effort. This study aimed to develop a deep learning model using the RCFT and based on eye tracking to detect impaired executive function during visuospatial memory encoding in patients with mental illnesses. In 96 patients with first-episode psychosis, 49 with clinical high risk for psychosis, 104 with OCD, and 159 healthy controls, eye movements were recorded during a 3-min RCFT figure memorization task, and organization and immediate recall scores were obtained. These scores, along with the fixation points indicating eye-focused locations in the figure, were used to train a Long Short-Term Memory + Attention model for detecting impaired executive function and visuospatial memory. The model distinguished between normal and impaired executive function, with an F 1 score of 83.5%, and identified visuospatial memory deficits, with an F 1 score of 80.7%, regardless of psychiatric diagnosis. These findings suggest that this eye tracking-based deep learning model can directly and rapidly identify impaired executive function during visuospatial memory encoding, with potential applications in various psychiatric and neurological disorders.

Abstract Cone-beam computed tomography (CBCT) has proven to be a safe and effective adjunctive imaging tool for interventional radiology. Nevertheless, limited studies have examined the application of CBCT in renal artery embolization (RAE). The objective of this study is to evaluate the role of CBCT in intra-procedural decision-making for RAE. This multicenter retrospective study included 40 consecutive patients (age: 55.9 ± 16.5 years; male, 55%) who underwent CBCT during RAE from January 2019 to January 2023. The additional information provided by CBCT was classified into Category 1 (no additional information), Category 2 (more information without changing the treatment plan), and Category 3 (valuable information that led to a change in the treatment plan). CBCT did not add unique information for four patients (10%) classified as Category 1. CBCT clarified ambiguous angiographic findings and confirmed the existing treatment plan for 19 patients (47.5%) graded as Category 2; complex vascular anatomy was explained (n = 13), and a correlation between vascular territory and target lesion was established (n = 6). CBCT offered valuable information that was not visible on digital subtraction angiography and changed the treatment plan for 17 patients categorized as Category 3; a mismatch between the vascular territory and the target lesion led to the identification of alternative (n = 3) and additional feeders (n = 8); and the extent of embolization was reduced by using automatic feeder detection software (n = 6). CBCT is an efficient tool that aids in the decision-making process during the embolization procedure by providing supplementary imaging information. This additional information enables the confident identification of target vessels, facilitates superselective embolization, prevents non-target embolization, and helps locate missing feeders.

Abstract This study aimed to develop and evaluate a deep learning-based system for the automatic measurement of angles (specifically, Meary’s angle and calcaneal pitch) in weight-bearing lateral radiographs of the foot for flatfoot diagnosis. We utilized 3960 lateral radiographs, either from the left or right foot, sourced from a pool of 4000 patients to construct and evaluate a deep learning-based model. These radiographs were captured between June and November 2021, and patients who had undergone total ankle replacement surgery or ankle arthrodesis surgery were excluded. Various methods, including correlation analysis, Bland–Altman plots, and paired T-tests, were employed to assess the concordance between the angles automatically measured using the system and those assessed by clinical experts. The evaluation dataset comprised 150 weight-bearing radiographs from 150 patients. In all test cases, the angles automatically computed using the deep learning-based system were in good agreement with the reference standards (Meary’s angle: Pearson correlation coefficient (PCC) = 0.964, intraclass correlation coefficient (ICC) = 0.963, concordance correlation coefficient (CCC) = 0.963, p-value = 0.632, mean absolute error (MAE) = 1.59°; calcaneal pitch: PCC = 0.988, ICC = 0.987, CCC = 0.987, p-value = 0.055, MAE = 0.63°). The average time required for angle measurement using only the CPU to execute the deep learning-based system was 11 ± 1 s. The deep learning-based automatic angle measurement system, a tool for diagnosing flatfoot, demonstrated comparable accuracy and reliability with the results obtained by medical professionals for patients without internal fixation devices.

Abstract We investigated the long-term patterns and effects of transfusion on the clinical outcome of patients undergoing percutaneous coronary intervention (PCI) using a nationwide registry. Five-year clinical outcome of all Koreans undergoing PCI using stent in year 2011 (n = 48,786) was investigated. Primary outcome was the incidence density of transfusion. The association of transfusion with major adverse clinical event (MACE) consisting all-cause death, revascularization, critically ill cardiovascular status, or stroke was assessed after adjusting the propensity of each patient for transfusion. The 5-year incidence density of transfusion was 4.74 (95% confidence interval [CI] 4.70–4.79) per 100 person-year. Patients who received transfusion were older and had higher frequency of clinical risk factors (p

Abstract The bidirectional effect of hyperuricemia on chronic kidney disease (CKD) underscores the importance of hyperuricemia as a risk factor for CKD. We evaluated the effect of hyperuricemia on the presence and development of CKD after considering genetic background by calculating polygenic risk scores (PRSs). We employed genome-wide association study summary statistics—excluding the United Kingdom Biobank (UKB) datasets among published CKD Gen Consortium papers—to calculate the PRSs for CKD in white background subjects. To validate PRS performance, we divided the UKB into two datasets to validate and test the data. We used logistic regression analysis to evaluate the association between hyperuricemia and CKD, and performed Kaplan–Meier survival analysis exclusively for subjects with available follow-up data. In total, 438,253 clinical data and 4,307,940 single nucleotide polymorphisms from 459,155 samples were included. We observed a significant positive association between PRS and CKD and the presence and development of CKD. Hyperuricemia significantly increased CKD risk (adjusted odds ratio 1.55, 95% confidence interval 1.48–1.61). The impact of hyperuricemia on CKD was maintained irrespective of PRS range. In addition, negative interaction between hyperuricemia and PRS for CKD was found. Survival analysis indicates that the presence of hyperuricemia significantly increased the risk of CKD development. The PRS for CKD thoroughly reflects the risk of CKD development. Hyperuricemia is a significant indicator of CKD risk, even after incorporating the genetic risk score for CKD. Irrespective of genetic risk, patients with a prospective risk of developing CKD require uric acid monitoring and management.

Abstract CD73 is a cell-surface ectoenzyme that hydrolyzes the conversion of extracellular adenosine monophosphate to adenosine, which in turn can promote resistance to immune checkpoint blockade therapy. Immune response may therefore be improved by targeting tumor CD73, and this possibility underlines the need to non-invasively assess tumor CD73 level. In this study, we developed a cysteine site-specific 89Zr-labeled anti-CD73 (89Zr-CD73) IgG immuno-PET technique that can image tumor CD73 expression in living bodies. Anti-CD73 IgG was reduced with tris(2-carboxyethyl)phosphine, underwent sulfohydryl moiety–specific conjugation with deferoxamine–maleimide, and was radiolabeled with 89Zr. CT26 mouse colon cancer cells, CT26/CD73 cells engineered to constitutively overexpress CD73, and 4T1.2 mouse breast cancer cells underwent cell binding assays and western blotting. Balb/c nude mice bearing tumors underwent 89Zr-CD73 IgG PET imaging and biodistribution studies. 89Zr-CD73 IgG showed 20-fold higher binding to overexpressing CT26/CD73 cells compared to low-expressing CT26 cells, and moderate expressing 4T1.2 cells showed uptake that was 38.9 ± 1.51% of CT26/CD73 cells. Uptake was dramatically suppressed by excess unlabeled antibody. CD73 content proportionately increased in CT26 and CT26/CD73 cell mixtures was associated with linear increases in 89Zr-CD73 IgG uptake. 89Zr-CD73 IgG PET/CT displayed clear accumulation in CT26/CD73 tumors with greater uptake compared to CT26 tumors (3.13 ± 1.70%ID/g vs. 1.27 ± 0.31%ID/g at 8 days; P = 0.04). Specificity was further supported by low CT26/CD73 tumor-to-blood ratio of 89Zr-isotype-IgG compared to 89Zr-CD73 IgG (0.48 ± 0.08 vs. 2.68 ± 0.52 at 4 days and 0.53 ± 0.07 vs. 4.81 ± 1.02 at 8 days; both P

Abstract Neuromorphic computing research is being actively pursued to address the challenges posed by the need for energy-efficient processing of big data. One of the promising approaches to tackle the challenges is the hardware implementation of spiking neural networks (SNNs) with bio-plausible learning rules. Numerous research works have been done to implement the SNN hardware with different synaptic plasticity rules to emulate human brain operations. While a standard spike-timing-dependent-plasticity (STDP) rule is emulated in many SNN hardware, the various STDP rules found in the biological brain have rarely been implemented in hardware. This study proposes a CMOS-memristor hybrid synapse circuit for the hardware implementation of a Ca ion-based plasticity model to emulate the various STDP curves. The memristor was adopted as a memory device in the CMOS synapse circuit because memristors have been identified as promising candidates for analog non-volatile memory devices in terms of energy efficiency and scalability. The circuit design was divided into four sub-blocks based on biological behavior, exploiting the non-volatile and analog state properties of memristors. The circuit was designed to vary weights using an H-bridge circuit structure and PWM modulation. The various STDP curves have been emulated in one CMOS-memristor hybrid circuit, and furthermore a simple neural network operation was demonstrated for associative learning such as Pavlovian conditioning. The proposed circuit is expected to facilitate large-scale operations for neuromorphic computing through its scale-up.

Abstract There is limited evidence regarding the causal inference of emphysema and functional small airway disease in the subsequent progression of chronic obstructive pulmonary disease (COPD). Patients consisting of two independent cohorts diagnosed with COPD and underwent two serial chest CT scans were included. Total percent emphysema (PRMEmph) and fSAD (PRMfSAD) was quantified via PRM. To investigate the progression of emphysema, we divided COPD patients with PRMEmph

Abstract Fever of unknown origin (FUO) remains a formidable diagnostic challenge in the field of medicine. Numerous studies suggest an association between FUO and genetic factors, including chromosomal abnormalities. Here, we report a female patient with a 4.5 Mb Xp microdeletion, who presented with recurrent FUO, bacteremia, colitis, and hematochezia. To elucidate the underlying pathogenic mechanism, we employed a comprehensive approach involving single cell RNA sequencing, T cell receptor sequencing, and flow cytometry to evaluate CD4 T cells. Analysis of peripheral blood mononuclear cells revealed augmented Th1, Th2, and Th17 cell populations, and elevated levels of proinflammatory cytokines in serum. Notably, the patient exhibited impaired Treg cell function, possibly related to deletion of genes encoding FOPX3 and WAS. Single cell analysis revealed specific expansion of cytotoxic CD4 T lymphocytes, characterized by upregulation of various signature genes associated with cytotoxicity. Moreover, interferon-stimulated genes were upregulated in the CD4 T effector memory cluster. Further genetic analysis confirmed maternal inheritance of the Xp microdeletion. The patient and her mother exhibited X chromosome-skewed inactivation, a potential protective mechanism against extensive X chromosome deletions; however, the mother exhibited complete skewing and the patient exhibited incomplete skewing (85:15), which may have contributed to emergence of immunological symptoms. In summary, this case report describes an exceptional instance of FUO stemming from an incompletely inactivated X chromosome microdeletion, thereby increasing our understanding of the genetics underpinning FUO.