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Abstract The IL-23-Th17 axis is responsible for neutrophilic inflammation in various inflammatory diseases. Here, we discover a potential pathway to inhibit neutrophilic asthma. In our neutrophil-dominant asthma (NDA) model, single-cell RNA-seq analysis identifies a subpopulation of CD39+CD9+ interstitial macrophages (IMs) suppressed by IL-23 in NDA conditions but increased by an IL-23 inhibitor αIL-23p19. Adoptively transferred CD39+CD9+ IMs suppress neutrophil extracellular trap formation (NETosis), a representative phenotype of NDA, and also Th17 cell activation and neutrophilic inflammation. CD39+CD9+ IMs first attach to neutrophils in a CD9-dependent manner, and then remove ATP near neutrophils that contribute to NETosis in a CD39-dependent manner. Transcriptomic data from asthmatic patients finally show decreased CD39+CD9+ IMs in severe asthma than mild/moderate asthma. Our results suggest that CD39+CD9+ IMs function as a potent negative regulator of neutrophilic inflammation by suppressing NETosis in the IL-23-Th17 axis and can thus serve as a potential therapeutic target for IL-23-Th17-mediated neutrophilic asthma.

Background/Aims The association between inflammatory bowel disease (IBD) and gallstone and renal stone formation has been established. However, few studies have investigated this association in patients with intestinal Behçet’s disease (BD). We aimed to examine the prevalence of gallstones and renal stones in patients with intestinal BD and identify potential risk factors. Methods We analyzed gallstone and renal stone occurrences in 553 patients diagnosed with intestinal BD who had undergone cross-sectional imaging examinations between March 2005 and April 2021 at the IBD Center, Severance Hospital, Seoul, South Korea. Logistic regression models were used to identify risk factors for gallstone and renal stone formation. Results Of 553 patients over a mean 12.1-year duration, 141 (25.4%) patients had gallstones and 35 (6.3%) had renal stones. In multivariate logistic regression analysis, disease duration > 19 years (OR 2.91, 95% CI 1.56–5.44, p < 0.001), prior intestinal BD-related surgery (OR 2.29, 95% CI 1.42–3.68, p < 0.001), and disease activity index for intestinal BD scores ≥ 75 (OR 2.23, 95% CI 1.12–4.45, p = 0.022) were associated with increased gallstone occurrence. A positive correlation was observed between renal stones, disease duration > 19 years (OR 5.61, 95% CI 1.98–15.90, p = 0.001) and frequent hospitalization (> 3 times) (OR 3.29, 95% CI 1.52–7.13, p = 0.002). No significant correlation was observed between gallstone and renal stone occurrence. Conclusions These findings contribute to greater understanding concerning gallstone and renal stone prevalence and associated risk factors in patients with intestinal BD.

Background/Aims The impact of vaccination on inflammatory bowel disease (IBD) patients is still unknown, and no studies have assessed the changes in patient-reported outcomes (PROs) after vaccination in patients with IBD. Therefore, in this study, we investigated the impact of vaccines on the PROs of patients with IBD. Methods We conducted a questionnaire survey of patients with IBD who visited outpatient clinics at 4 specialized IBD clinics of referral university hospitals from April 2022 to June 2022. A total of 309 IBD patients were included in the study. Patient information was collected from a questionnaire and their medical records, including laboratory findings, were reviewed retrospectively. Risk factors associated with an increase in PROs after COVID-19 vaccination were analyzed using logistic regression analyses. In addition, we assessed whether there were differences in variables by vaccine order using the linear mixed model. Results In multivariate analysis, young age ( < 40 years) and ulcerative colitis (UC) were found to be independent risk factors for aggravation of PROs in patients with IBD. In all patients, platelet count significantly increased with continued vaccination in multiple pairwise comparisons. In UC patients, PROs such as the short health scale, UC-abdominal signs and symptoms, and UC-bowel signs and symptoms were aggravated significantly with continued vaccination. There was no significant increase in the variables of patients with Crohn’s disease. Conclusions Therefore, there may be a need to counsel patients with IBD younger than 40 years of age, and patients with UC before they receive COVID-19 vaccinations.

Background/Aims: Despite advances in imaging and endoscopic technology, diagnostic modalities for small bowel tumors are simultaneously performed. We investigated the discrepancy rate between each modality and predictive factors of discrepancy in patients with definite small bowel tumors. Methods: Data of patients with definite small bowel tumors who underwent both device-assisted enteroscopy (DAE) and computed tomography (CT) were retrieved from web-based enteroscopy registry database in Korea. Predictive risk factors associated with discrepancy were analyzed using logistic regression analysis. Results: Among 998 patients, 210 (21.0%) were diagnosed with small bowel tumor using DAE, in 193 patients with definite small bowel tumor, DAE and CT were performed. Of these patients, 12 (6.2%) showed discrepancy between examinations. Among 49 patients who underwent DAE and video capsule endoscopy (VCE) examination, 13 (26.5%) showed discrepancy between examinations. No significant independent risk factors were associated with concordance between DAE and CT in multivariate logistic regression analysis among the patients. In a multivariate logistic regression analysis, red blood cell transfusion was negatively associated with concordance between DAE and VCE in patients with small bowel tumor (odds ratio, 0.163; 95% confidence interval, 0.026 to 1.004; p=0.050). Conclusion : s: For small bowel tumors, the discrepancy rate between DAE and CT was 6.2%, and 26.5% between DAE and VCE. Despite developments in cross-sectional imaging (VCE and DAE modalities), discrepancies still exist. For small bowel bleeding that require significant transfusion while showing insignificant VCE findings, DAE should be considered as the next diagnostic approach, considering the possibility of missed small bowel tumor.

Abstract The pursuit of advanced brain‐inspired electronic devices and memory technologies has led to explore novel materials by processing multimodal and multilevel tailored conductive properties as the next generation of semiconductor platforms, due to von Neumann architecture limits. Among such materials, antimony sulfide (Sb2S3) thin films exhibit outstanding optical and electronic properties, and therefore, they are ideal for applications such as thin‐film solar cells and nonvolatile memory systems. This study investigates the conduction modulation and memory functionalities of Sb2S3 thin films deposited via the vapor transport deposition technique. Experimental results indicate that the Ag/Sb2S3/Pt device possesses properties suitable for memory applications, including low operational voltages, robust endurance, and reliable switching behavior. Further, the reproducibility and stability of these properties across different device batches validate the reliability of these devices for practical implementation. Moreover, Sb2S3‐based memristors exhibit artificial neuroplasticity with prolonged stability, promising considerable advancements in neuromorphic computing. Leveraging the photosensitivity of Sb2S3 enables the Ag/Sb2S3/Pt device to exhibit significant low operating potential and conductivity modulation under optical stimulation for memory applications. This research highlights the potential applications of Sb2S3 in future memory devices and optoelectronics and in shaping electronics with versatility.

Background and objective: Previous germline studies on renal cell carcinoma (RCC) have usually pooled clear and non–clear cell RCCs and have not adequately accounted for population stratification, which might have led to an inaccurate estimation of genetic risk. Here, we aim to analyze the major germline drivers of RCC risk and clinically relevant but underexplored germline variant types. Methods: We first characterized germline pathogenic variants (PVs), cryptic splice variants, and copy number variants (CNVs) in 1436 unselected RCC patients. To evaluate the enrichment of PVs in RCC, we conducted a case-control study of 1356 RCC patients ancestry matched with 16 512 cancer-free controls using approaches accounting for population stratification and histological subtypes, followed by characterization of secondary somatic events. Key findings and limitations: Clear cell RCC patients (n = 976) exhibited a significant burden of PVs in VHL compared with controls (odds ratio [OR]: 39.1, p = 4.95e-05). Non–clear cell RCC patients (n = 380) carried enrichment of PVs in FH (OR: 77.9, p = 1.55e-08) and MET (OR: 1.98e11, p = 2.07e-05). In a CHEK2-focused analysis with European participants, clear cell RCC (n = 906) harbored nominal enrichment of low-penetrance CHEK2 variants—p.Ile157Thr (OR: 1.84, p = 0.049) and p.Ser428Phe (OR: 5.20, p = 0.045), while non–clear cell RCC (n = 295) exhibited nominal enrichment of CHEK2 loss of function PVs (OR: 3.51, p = 0.033). Patients with germline PVs in FH, MET, and VHL exhibited significantly earlier age of cancer onset than patients without germline PVs (mean: 46.0 vs 60.2 yr, p

Background/Aims: Increased prevalence of nonalcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) has been reported. However, the effects of NAFLD on the outcome of IBD remains unclear. We investigated whether the presence of NAFLD could influence the outcomes of patients with IBD. Methods : We recruited 3,356 eligible patients with IBD into our study between November 2005 and November 2020. Hepatic steatosis and fibrosis were diagnosed using hepatic steatosis index of ≥30 and fibrosis-4 of ≥1.45, respectively. The primary outcome was clinical relapse, defined based on the following: IBD-related admission, surgery, or first use of corticosteroids, immunomodulators, or biologic agents for IBD. Results : The prevalence of NAFLD in patients with IBD was 16.7%. Patients with hepatic steatosis and advanced fibrosis were older, had a higher body mass index, and were more likely to have diabetes (all p

Abstract Background Environmental exposure, medical diagnostic and therapeutic applications, and industrial utilization of radionuclides have prompted a growing focus on the risks associated with low-dose radiation (

Long Short-Term Memory (LSTM) networks, coupled with attention mechanisms, have demonstrated their proficiency in handling time-series data, particularly in the architectural energy prediction industry. However, their high computational complexity and resource-intensive nature pose significant challenges for real-time applications and on edge devices. Traditional methods of mitigating these issues, such as quantization, often lead to a compromise on model performance due to approximation errors introduced during the process. In this paper, we propose Q-LAtte, a novel, quantization-friendly attention-based LSTM model, as a solution to these challenges. Q-LAtte incorporates an innovative approach to quantization that preserves the efficiency benefits while significantly reducing the performance degradation typically associated with standard quantization techniques. The key to its superior performance lies in its distribution-aware quantization process. By effectively conserving the output distribution of the model parameters before and after quantization, Q-LAtte ensures the retention of subtle but significant variations integral to decision-making processes like prediction or classification. Compared to traditional quantized models, Q-LAtte exhibits a notable improvement in performance. Specifically, our method reduces the Mean Average Percentage Error (MAPE) from 17.56 to 8.48 and the Mean Absolute Scaled Error (MASE) by 48%, while minimizing the time cost. These results highlight the efficacy of Q-LAtte in striking a balance between efficiency and accuracy, significantly enhancing the feasibility of deploying attention-LSTM networks on resource-constrained devices for real-time, on-site data analysis and decision-making.

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents, including n-hexane (EHex), chloroform (ECHCl3), ethyl acetate (EEA), n-butyl alcohol (EBuOH), and water (EDW). Ethyl acetate fraction (EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines (IL-6 and TNF-α) in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-and di-glycoside of each aglycone. The main flavonol form of EEA is the mono-glycoside of each aglycone detected, and the most abundant flavonol mono-glycoside is kaempferol 3-glucoside 7.4%, followed by quercetin-3-glucoside 2.3% and isorhamnetin 3-glucoside 1.4%. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that the flavonol composition of E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

Abstract Background Brain metastasis is a common complication among patients with lung cancer, yet the underlying mechanisms remain unclear. In this study, we aimed to investigate the pathogenesis of brain metastasis in lung cancer. Methods We established highly colonizing metastatic lung cancer cells, A549-M2, through multiple implantations of A549 human lung cancer cells in the carotid artery of athymic nude mice. Results Compared to parental cells (M0), M2 cells demonstrated slower growth in culture plates and soft agar, as well as lower motility and higher adhesion, key characteristics of mesenchymal–epithelial transition (MET). Further analysis revealed that M2 cells exhibited decreased expression of epithelial–mesenchymal transition markers, including ZEB1 and Vimentin. M2 cells also demonstrated reduced invasiveness in co-culture systems. RNA sequencing and gene set enrichment analysis confirmed that M2 cells underwent MET. Intriguingly, depletion of Noggin, a BMP antagonist, was observed in M2 cells, and replenishment of Noggin restored suppressed migration and invasion of M2 cells. In addition, Noggin knockdown in control M0 cells promoted cell attachment and suppressed cell migration, suggesting that Noggin reduction during brain colonization causes inhibition of migration and invasion of metastatic lung cancer cells. Conclusions Our results suggest that lung cancer cells undergo MET and lose their motility and invasiveness during brain metastatic colonization, which is dependent on Noggin.

Nanofiber (NF) membrane systems that can provide cascade catalytic reaction and ferroptosis induction were developed for oral cancer therapy. Glucose oxidase (GOx) and aminoferrocene (AF) were introduced into the NF system for glucose deprivation/H2O2 generation and OH radical generation, respectively. GOx offers starvation therapy and AF (including iron) provides chemodynamic therapy/ferroptosis for combating oral cancer. GOx (water-soluble) and AF (poorly water-soluble) molecules were successfully entrapped in the NF membrane via an electrospinning process. GOx and AF were incorporated into the polyvinyl alcohol (PVA)-based NF, resulting in PVA/GOx/AF NF with fast disintegration and immediate drug-release properties. In oral squamous cell carcinoma (YD-9 cells), the PVA/GOx/AF NF group exhibited higher cytotoxicity, antiproliferation potential, cellular ROS level, apoptosis induction, lipid ROS level, and malondialdehyde level compared to the other NF groups. The electrospun PVA/GOx/AF NF can be directly applied to oral cancer without causing pain, offering starvation/chemodynamic therapy and ferroptosis induction.

Background/Aims Patients with more than 10 cumulative polyps might involve a greater genetic risk of colorectal neoplasia development. However, few studies have investigated the risk factors of polyposis recurrence and development of advanced neoplasms among patients with non-hereditary colorectal polyposis. Methods This study included patients (n=855) with 10 or more cumulative polyps diagnosed at Severance Hospital from January 2012 to September 2021. Patients with known genetic mutations related to polyposis, known hereditary polyposis syndromes, insufficient information, total colectomy, and less than 3 years of follow-up were excluded. Finally, 169 patients were included for analysis. We collected clinical data, including colonoscopy surveillance results, and performed Cox regression analyses of risk factors for polyposis recurrence and advanced neoplasm development. Results The 169 patients were predominantly male (84.02%), with a mean age of 64.19±9.92 years. The mean number of adenomas on index colonoscopy was 15.33±8.47. Multivariable analysis revealed history of cancer except colon cancer (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.23–4.01), current smoking (HR, 2.39; 95% CI, 1.17–4.87), and detection of many polyps (≥15) on index colonoscopy (HR, 2.05; 95% CI, 1.21–3.50) were significant risk factors for recurrence of polyposis. We found no statistically significant risk factors for advanced neoplasm development during surveillance among our cohort. Conclusions The presence of many polyps (≥15) on index colonoscopy, history of cancer except colon cancer, and current smoking state were significant risk factors for polyposis recurrence among patients with non-hereditary colorectal polyposis.

Abstract Pathological markers that can monitor the progression of gastric cancer (GC) may facilitate the diagnosis and treatment of patients with diffuse GC (DGC). To identify microRNAs (miRNAs) that can differentiate between early and advanced DGC in the gastric mucosa, miRNA expression profiling was performed using the NanoString nCounter method in human DGC tumors. Ectopic expression of miR-199a and miR-199b (miR-199a/b) in SNU601 human GC cells accelerated the growth rate, viability, and motility of cancer cells and increased the tumor volume and weight in a mouse xenograft model. To study their clinicopathological roles in patients with GC, miR-199a/b levels were measured in human GC tumor samples using in situ hybridization. High miR-199a/b expression level was associated with enhanced lymphovascular invasion, advanced T stage, and lymph-node metastasis. Using the 3′-untranslated region (UTR) luciferase assay, Frizzled-6 (FZD6) was confirmed to be a direct target of miR-199a/b in GC cells. siRNA-mediated depletion of FZD6 enhanced the motility of SNU601 cells, and addback of FZD6 restored cancer cell motility stimulated by miR-199a/b. In conclusion, miR-199a/b promotes DGC progression by targeting FZD6, implying that miR-199a/b can be used as prognostic and diagnostic biomarkers for the disease.

Abstract Despite recent advancements in mechanochemical polymerization, understanding the unique mechanochemical reactivity during the ball milling polymerization process still requires extensive investigations. Herein, solid-state anionic ring-opening polymerization is used to synthesize polyethers from various functional epoxide monomers. The critical parameters of the monomers are investigated to elucidate the unique reactivity of ball milling polymerization. The controllable syntheses of the desired polyethers are characterized via NMR, GPC, and MALDI-ToF analyses. Interestingly, bulky monomers exhibit faster conversions in the solid-state in clear contrast to that observed for solution polymerization. Particularly, a close linear correlation is observed between the conversion of the ball milling polymerization and melting point of the functional epoxide monomers, indicating melting point as a critical predictor of mechanochemical polymerization reactivity. This study provides insights into the efficient design and understanding of mechanochemical polymerization.

Background/Aims: The clinical efficacy and safety of CT-P13 are comparable to originator infliximab for Crohn’s disease in CT-P13 3.4 study (NCT02096861). We performed a multivariate logistic analysis to demonstrate the association between early infliximab trough levels and treatment outcomes of CT-P13 and originator infliximab. Methods: Early serum infliximab trough levels and anti-drug antibody (ADA) levels were compared between CT-P13 (n=100) and originator infliximab (n=98) groups. Receiver operating characteristic (ROC) analysis and multivariate logistic analysis were conducted to identify optimal cutoffs of serum infliximab trough levels and predictive factors for clinical outcomes. Results: The median infliximab trough levels were not different between CT-P13 and originator infliximab groups at week 6, week 14, and in median ADA levels at week 14, respectively. ROC analysis found an infliximab concentration threshold of 4.5 μg/mL at week 6 and 4.0 μg/mL at week 14 as the cutoff value with the highest accuracy for the prediction of clinical outcomes. Serum infliximab trough levels at weeks 6 and 14 predicted clinical remission at weeks 30 and 54, and endoscopic remission at week 54. The combinations of clinical remission or C-reactive protein normalization with an early infliximab trough level improved the prediction of long-term clinical or endoscopic remission. Conclusions: A threshold in serum infliximab trough level at week 6 and week 14 was highly predictive for long-term clinical outcomes. There were no statistical differences in serum infliximab trough levels and ADA levels between CT-P13 and originator infliximab.

Background: Notably, 5-aminosalicylates (5-ASA) are vital in treating inflammatory bowel diseases (IBD). The adverse events of 5-ASA rarely occur but they could be fatal. Objectives: We aimed to discover new genetic biomarkers predicting 5-ASA-induced adverse events in patients with IBD. Design: This was a retrospective observational study. Methods: We performed a genome-wide association study on patients with IBD in South Korea. We defined subset 1 as 39 all adverse events and 272 controls; subset 2 as 20 severe adverse events and 291 controls (mild adverse events and control); subset 3 as 20 severe adverse events and 272 controls; and subset 4 as 19 mild adverse events and 272 controls. Logistic regression analysis was performed and commonly found associated genes were determined as candidate single-nucleotide polymorphisms predicting 5-ASA adverse events. Results: Patients with Crohn’s disease (CD) were significantly negatively associated with the development of adverse events compared to patients with ulcerative colitis (UC) (5.3% versus 22.9%). However, sex and age at diagnosis were unassociated with the adverse events of 5-ASA. rs13898676 [odds ratio (OR), 20.33; 95% confidence interval (CI), 5.69–72.67; p = 3.57 × e −6 ], rs12681590 (OR, 7.35; 95% CI, 2.85–19.00; p = 3.78 × e −5 ), rs10967320 (OR, 4.51; 95% CI, 2.18–9.31; p = 4.72 × e −5 ), and rs78726924 (OR, 3.54; 95% CI, 1.69–7.40; p = 7.96 × e −5 ) were genetic biomarkers predicting 5-ASA-induced severe adverse events in patients with IBD. Conclusion: The adverse events of 5-ASA were more common in patients with UC than those with CD in our study. We found that novel rs13898676 nearby WSB2 was the most significant genetic locus contributing to 5-ASA’s adverse event risk.

Recently, temporal muscle thickness (TMT) has been investigated as a novel surrogate marker for muscle mass and function in neurologic patients. This study aimed to assess the correlation of TMT with grip strength to establish a new parameter for predicting pre-stroke sarcopenia. A total of 358 patients who were newly diagnosed with acute ischemic stroke at our institution between November 2021 and August 2022 were enrolled. Eighty-four patients met the eligibility criteria. The mean TMT was measured within initial brain MRI using previously described methods. Pearson's correlation analyses assessed the relationship between grip strength and TMT. Multiple logistic regression analyses were performed to identify associations between TMT and other associated factors including grip strength, sarcopenia risk, body mass index, age, Charlson Comorbidity Index and Geriatric nutrition risk index. Mean TMT values indicated a strong correlation with the grip strength of the non-hemiplegic hand in both male and female patients. Multiple logistic regression analyses showed that TMT was associated with grip strength and sarcopenia risk in hemiplegic patients. Measuring TMT using cranial MR images during the initial stages of stroke could help predict a patient's pre-stroke muscle strength status. Further studies are required to apply TMT in pre-stroke sarcopenia diagnosis.

Abstract Background Clonal haematopoiesis of indeterminate potential (CHIP) is a predisposition to haematological malignancy whose relationship with chronic inflammatory diseases, such as cardiovascular diseases, has been highlighted. Here, we aimed to investigate the CHIP emergence rate and its association with inflammatory markers in Behçet’s disease (BD). Methods We performed targeted next-generation sequencing to detect the presence of CHIP using peripheral blood cells from 117 BD patients and 5004 healthy controls between March 2009 and September 2021 and analysed the association between CHIP and inflammatory markers. Results CHIP was detected in 13.9% of patients in the control group and 11.1% of patients in the BD group, indicating no significant intergroup difference. Among the BD patients of our cohort, five variants (DNMT3A, TET2, ASXL1, STAG2, and IDH2) were detected. DNMT3A mutations were the most common, followed by TET2 mutations. CHIP carriers with BD had a higher serum platelet count, erythrocyte sedimentation rate, and C-reactive protein level; older age; and lower serum albumin level at diagnosis than non-CHIP carriers with BD. However, the significant association between inflammatory markers and CHIP disappeared after the adjustment for various variables, including age. Moreover, CHIP was not an independent risk factor for poor clinical outcomes in patients with BD. Conclusions Although BD patients did not have higher CHIP emergence rates than the general population, older age and degree of inflammation in BD were associated with CHIP emergence.

Abstract Treatment of paroxysmal nocturnal haemoglobinuria (PNH) includes the monoclonal antibody eculizumab. This randomised, double‐blind, multi‐national cross‐over Phase III study in PNH patients aimed to demonstrate the equivalence of the proposed eculizumab biosimilar SB12 and reference eculizumab (Soliris, ECU). PNH patients with lactate dehydrogenase (LDH) ≥1·5× upper limit of normal were randomised into treatment sequences SB12‐ECU or ECU‐SB12. Four weekly infusions of 600 mg eculizumab were followed by fortnightly infusions of 900 mg until week 50 (ECU/SB12 cross‐over at week 26). Primary endpoints were LDH at week 26 and the time‐adjusted area under the effect curve (AUEC) of LDH over weeks 14‒26 and 40‒52. Among 46 patients (92%) who completed the study, the least squares mean (LSM) difference in LDH at week 26 (34·48; 95% confidence interval [CI] −47·66‒116·62 U/l) and geometric LSM ratio of time‐adjusted AUEC of LDH (1·08; 90% CI 0·95‒1·23) were within pre‐defined equivalence margins. Mean numbers of transfused red blood cell units, other secondary endpoints, pharmacokinetics, and pharmacodynamics were comparable. No patients developed anti‐drug antibodies. Treatment‐emergent adverse events were reported in 72% and 68% of patients in the SB12 and ECU treatment groups, respectively. The results demonstrate equivalence of SB12 to ECU and support SB12‐use in PNH patients.

Abstract Indocyanine green (ICG), glucose oxidase (GOx), and copper(II) sulfate (Cu)‐installed hybrid gel based on organic nanorod (cellulose nanocrystal [CNC]) and inorganic nanodisk (Laponite [LAP]) was developed to perform a combination of starvation therapy (ST), chemodynamic therapy (CDT), and photothermal therapy (PTT) for localized cancers. A hybrid CNC/LAP network with a nematic phase was designed to enable instant gelation, controlled viscoelasticity, syringe injectability, and longer in vivo retention. Moreover, ICG was introduced into the CNC/LAP gel system to induce hyperthermia of tumor tissue, amplifying the CDT effect; GOx was used for glucose deprivation (related to the Warburg effect); and Cu was introduced for hydroxyl radical generation (based on Fenton‐like chemistry) and cellular glutathione (GSH) degradation in cancer cells. The ICG/GOx/Cu‐installed CNC/LAP gel in combination with near‐infrared (NIR) laser realized improved antiproliferation, cellular reactive oxygen species (ROS) generation, cellular GSH degradation, and apoptosis induction in colorectal cancer (CT‐26) cells. In addition, local injection of the CNC/ICG/GOx/Cu/LAP gel into the implanted CT‐26 tumor while irradiating it with NIR laser provided strong tumor growth suppression effects. In conclusion, the designed hybrid nanorod/nanodisk gel network can be efficiently applied to the local PTT/ST/CDT of cancer cells.

Background: Methotrexate monotherapy is recommended as a maintenance therapy for Crohn’s disease (CD). However, long-term follow-up data are scarce. Objectives: We aimed to examine the effectiveness and tolerability of methotrexate monotherapy in 94 CD patients from three inflammatory bowel disease Clinics in Korea. Design: This was a multicenter retrospective observational study. Methods: Patients with active CD treated with methotrexate monotherapy were included. Clinical characteristics, laboratory indicators, endoscopy indices were evaluated at baseline, 6, 12, and 24 months. Independent factors associated with long-term clinical and endoscopic outcomes were determined. Results: Methotrexate was administered orally (70.2%) or parenterally (29.8%). The mean methotrexate induction dose was 15.3 ± 0.4 mg/week, and the mean duration of therapy was 26.2 months. Of 76 patients who were treated for >6 months, the clinical remission rates were 76.3%, 74.6%, and 80.0% at 6, 12, and 24 months, respectively, by per-protocol analysis. The mean CRP levels were 7.5 ± 1.3, 5.3 ± 1.2, 3.8 ± 0.7, and 2.6 ± 0.5 mg/L at 0, 6, 12, and 24 months, respectively. Of 31 patients who underwent follow-up endoscopy after 27.5 months, the endoscopic remission rate was 38.7%. Baseline hemoglobin level

Background Pleurisy is an inflammation of the parietal pleura and is characterized by pleuritic pain. The most common cause of pleurisy is infection; other causes include rheumatoid arthritis, malignancy, rib fractures, or trauma. Possible causes of chest pain associated with golf include costochondritis, stress fractures of the ribs, intercostal muscle strain, or, rarely, Tietze’s syndrome and slipping rib syndrome. Case A 64-year-old female presented with intractable chest pain that began 4 months prior while playing golf. No specific cause was found after various examinations. There was persistent pain despite medical treatment. Ultrasonography (US) was performed over the painful areas, which revealed focal pleural effusions. A mixture of ropivacaine and triamcinolone was injected into the focal pleural effusions using US guidance, which dramatically relieved her pain. Conclusions This case demonstrates that US can be used as a diagnostic and therapeutic modality for intractable chest pain with an undetected pathology.

The introduction of device-assisted enteroscopy (DAE) in the beginning of 21st century has revolutionized the diagnosis and treatment of diseases of the small intestine. In contrast to capsule endoscopy, the other main diagnostic modality of the small bowel diseases, DAE has the unique advantages of observing the region of interest in detail and enabling tissue acquisition and therapeutic intervention. As DAE becomes an essential procedure in daily clinical practice, there is an increasing need for correct guidelines on when and how to perform it and what technical factors should be considered. In response to these needs, the Korean Association for the Study of Intestinal Diseases developed an expert consensus statement on the performance of DAE by reviewing the current evidence. This expert consensus statement particularly focuses on the indications, choice of insertion route, therapeutic intervention, complications, and relevant technical points.

Background/Aims We evaluated the gut microbiome using extracellular vesicles (EVs) in the urine of patients with colorectal cancer (CRC) to determine whether gut-microbe-derived EVs could be a potential biomarker for the diagnosis of CRC. Methods EVs were isolated from the urine of patients with CRC and healthy controls. DNA was extracted from the EVs, and the bacterial composition was analyzed using next-generation sequencing of the 16S rRNA. Results A total of 91 patients with CRC and 116 healthy controls were enrolled. We found some specific microbiomes that were more or less abundant in the CRC group than in the control group. The alpha-diversity of the gut microbiome was significantly lower in the CRC group than in the control group. A significant difference was observed in the beta-diversity between the groups. The alpha-diversity indices between patients with early- and late-stage CRC showed conflicting results; however, there was no significant difference in the beta-diversity according to the stage of CRC. There was no difference in the alpha- and beta-diversity of the gut microbiome corresponding to the location of CRC (proximal vs. distal). Conclusions A distinct gut microbiome is reflected in the urine EVs of patients with CRC compared with that in the healthy controls. Microbial signatures from EVs in urine could serve as potential biomarkers for the diagnosis of CRC.

The introduction of device-assisted enteroscopy (DAE) in the beginning of the 21st century has revolutionized the diagnosis and treatment of diseases of the small intestine. In contrast to capsule endoscopy, the other main diagnostic modality of small bowel diseases, DAE has the unique advantages of allowing the observation of the region of interest in detail and enabling tissue acquisition and therapeutic intervention. As DAE becomes an essential procedure in daily clinical practice, there is an increasing need for correct guidelines on when and how it is to be performed and what technical factors should be taken into consideration. In response to these needs, the Korean Association for the Study of Intestinal Diseases has developed an expert consensus statement on the performance of DAE by reviewing current evidence. This expert consensus statement particularly focuses on the indications, choice of insertion route, therapeutic intervention, complications, and relevant technical points.

Background/Aims: Golimumab has been used for patients with ulcerative colitis (UC) since 2013. However, there is limited data on the effectiveness and safety of the real-world use of golimumab in Asian patients. Methods: This was a multicenter, prospective, observational study. We enrolled patients with moderate-to-severe UC who were administered subcutaneous golimumab at 46 medical centers between May 2014 and November 2019. The primary outcome was the effectiveness and safety of golimumab at week 22. Clinical outcomes and adverse events were assessed according to partial Mayo score at weeks 0, 2, 6, 14, and 22. Results: A total of 130 patients were included (mean age: 45.7±16.0 years). The clinical response/ remission rates at weeks 2, 6, 14, and 22 were 40.4%/22.9%, 56.0%/35.8%, 70.6%/49.5%, and 67.9%/48.6%, respectively. Based on full Mayo score at week 14, clinical response and remission rates were 84.2% and 39.5%, respectively. Mucosal healing rate was 65.8%. In multivariate analysis with logistic regression, longer disease duration was significantly associated with a higher clinical response rate (adjusted odds ratio [aOR], 1.136; 95% confidence interval [CI], 1.006 to 1.282; p=0.040 at week 6; aOR, 1.256; 95% CI, 1.049 to 1.503; p=0.013 at week 22). A higher baseline Mayo endoscopic subscore was significantly associated with a lower clinical response rate at week 6 (aOR, 0.248; 95% CI, 0.089 to 0.692; p=0.008). The incidence of adverse drug reactions was 4.6% (6/130, nine events). No serious unexpected adverse drug reactions or deaths were reported. Conclusions: Golimumab was effective and safe as an induction and maintenance treatment for Korean patients with moderate-to-severe UC.

The incidence and prevalence of inflammatory bowel diseases (IBDs) are rapidly increasing worldwide. IBDs are considered an emerging problem not only in Western countries but also in developing counties. The relapses and complications of active IBD mandate various medications. Nevertheless, hospitalization, emergency room visits, or surgery may be required, resulting in a socioeconomic burden. Great advances have been made in the development of new therapeutic options for IBD to achieve induction and maintenance remission. Nevertheless, conventional therapy is still the mainstay in the treatment of IBD. This review article provides an update on recent advances in conventional therapies, including 5-aminosalicylates, corticosteroids, immunomodulators, and anti-tumor necrosis factor-α agents to treat IBD.

Indoor air quality (IAQ) directly affects human health. The increase in PM and CO2 concentration indoors caused an increase in the prevalence of sick building syndrome (SBS) symptoms. Plants could contribute to reducing particulate matter (PM) and CO2. This study identifies the most efficient evergreen plant species for improving indoor air quality by assessing the ability of five different indigenous Korean evergreen plant species to reduce PM and CO2 and regulate humidity and temperature under indoor environmental conditions in acrylic chambers. The clean air delivery rates (CADR) were calculated to evaluate the efficacy of plants in reducing PM and CO2. We assessed the performance of removing the five study plants on PM1 (~0.68–3.01 m3/h/leaf area), PM2.5 (~0.73–3.08 m3/h/leaf area), PM10 (~0.67–3.04 m3/h/leaf area), and CO2 (~0.48–1.04 m3/h/leaf area). The species Ilex pedunculosa, Pittosporum tobira, and Gardenia jasminoides were the most effective at reducing PM. The CADR of CO2 also differed among the five plant species and corresponded to their photosynthetic rate. Viburnum odoratissimum var. awabuki, which had the high photosynthetic rate, was most effective at reducing CO2. By contrast, PM reduction was correlated with plant leaf structure. Plants with a high leaf density can accumulate more PM. The plants were also able to control temperature and humidity. The average temperature of the control chamber was higher, and the humidity was lower than that of the plant chambers. In this study, the five evergreen species effectively reduced air pollutants and can be used to improve IAQ.

Background/Aims: Many patients with Crohn’s disease (CD) undergo intestinal resection during the disease course. Despite surgery, postoperative recurrence (POR) commonly occurs. Although postoperative use of tumor necrosis factor α (TNF-α) inhibitors is known to be effective in preventing POR, few studies have evaluated the effectiveness of continuing the same TNF-α inhibitors postoperatively in patients who received TNF-ɑ inhibitors before surgery. Methods: This retrospective observational study was performed in a single tertiary medical center. We retrospectively reviewed patients who had undergone the first intestinal resection due to CD and divided them into two groups: TNF-α inhibitor users in both the preoperative and postoperative periods, and TNF-α inhibitor users in only the preoperative period. We compared the clinical outcomes between these two groups. Results: In total, 45 patients who used TNF-α inhibitors preoperatively were recruited. Among them, TNF-α inhibitors were used postoperatively in 20 patients (44.4%). The baseline characteristics except age at diagnosis were similar in both groups. The rates of surgical and endoscopic recurrence were not different between the two groups, but the cumulative clinical recurrence rate was significantly lower in the postoperative TNF-α inhibitors group (log-rank p=0.003). In multivariate Cox regression analysis, postoperative TNF-α inhibitors use was significantly associated with a decreased risk of clinical recurrence (adjusted hazard ratio, 0.204; 95% confidence interval, 0.060 to 0.691; p=0.011). Conclusions: Continuing TNF-α inhibitors postoperatively in patients who were receiving TNF-α inhibitors before surgery significantly reduced the rate of clinical recurrence. For patients with CD who received TNF-α inhibitors preoperatively, continuing their use after surgery could be recommended.

Background/Aims The optimal tools for monitoring Crohn’s disease (CD) are controversial. We compared radiology plus ileocolonoscopy and radiology alone in terms of prognosis prediction and evaluated the agreement between radiologic and ileocolonoscopic findings in patients with CD. Methods Patients with CD who were followed up with computed tomography enterography (CTE) or magnetic resonance enterography (MRE) alone or CTE or MRE plus ileocolonoscopy were retrospectively recruited. Time to relapse was investigated to evaluate the difference in prognosis using the log-rank and Cox regression tests, and the agreement between radiologic and ileocolonoscopic findings was determined using a kappa value. Results A total of 501 patients with CD in clinical remission who underwent CTE or MRE and/or ileocolonoscopy were analyzed. Of these, 372 (74.3%) patients underwent CTE or MRE alone and 129 (25.7%) patients underwent CTE or MRE plus ileocolonoscopy. The cumulative maintenance rate of clinical remission between the two groups was not significantly different (p = 0.526, log-rank test). In multivariate analysis, age

The corrosion mechanism and kinetics of the silver-coated conductive yarn (SCCY) used for wearable electronics were investigated under a NaCl solution, a main component of sweat. The corrosion occurs according to the mechanism in which silver reacts with chlorine ions to partly form sliver chloride on the surface of the SCCY and then the local silver chloride is detached into the electrolyte, leading to the electrical disconnect of the silver coating. Thus, the electrical conductance of the SCCY goes to zero after 2.7 h. The radial part-coating of gold, which is continuously electrodeposited in the longitudinal direction on the SCCY but is partly electrodeposited in the radial direction, extends the electrical conducting lifetime up to 192 h, despite the corrosion rate increasing from 129 to 196 mpy (mils per year). Results show that the gold partly-coating on the SCCY provides a current path for electrical conduction along the longitudinal direction until all the silver underneath the gold coating is detached from the SCCY strands, which creates the electrical disconnect. Based on the corrosion behavior, i.e., local oxidation and detachment of silver from the SCCY, the gold part-coating is more cost effective than the gold full-coating electrodeposited on the entire surface for electrically conducting SCCY.

Abstract Background Therapeutic options for inflammatory bowel disease (IBD) have increased since the introduction of tumour necrosis factor (TNF) inhibitors a few decades ago. However, direct comparisons of the effectiveness of second-line biological agents in patients with ulcerative colitis (UC) and Crohn’s disease (CD) are lacking. Methods Patients with UC or CD who experienced anti-TNF treatment failure and subsequently used vedolizumab, ustekinumab, or tofacitinib as a second-line drug were retrospectively recruited. The primary outcomes were the clinical remission rate at week 16 and the cumulative relapse rate 48 weeks after receiving induction therapy. Results A total of 94 patients with UC or CD experienced anti-TNF treatment failure and received vedolizumab (UC: 37; CD: 28), ustekinumab (CD: 16), or tofacitinib (UC: 13). The clinical remission rates were not significantly different between the vedolizumab and tofacitinib groups in UC patients (56.8% vs. 46.2%, p = 0.509). In CD patients, the clinical remission rates were not significantly different between the vedolizumab and ustekinumab groups (53.6% vs. 50.0%, p = 0.820). Moreover, the cumulative rates of clinical relapse were not significantly different between the vedolizumab and tofacitinib groups in UC patients and between the vedolizumab and ustekinumab groups in CD patients (p = 0.396 and p = 0.692, respectively). Safety profiles were also similar among the treatment groups in both UC and CD patients. Conclusions After prior anti-TNF therapy failure, vedolizumab and tofacitinib in UC patients and vedolizumab and ustekinumab in CD patients were not significantly different in terms of the efficacy in inducing and maintaining a clinical response.

The Galileo High-Accuracy Service (HAS) was declared operational (initial service) in January 2023 after an intense testing phase aimed at assessing its service performance through the transmission of live HAS corrections. The HAS performance at high latitudes is evaluated by analyzing data collected at the Polish Polar Station located in Hornsund, in the Norwegian Svalbard archipelago. At such a location, the reception conditions can be affected by poor satellite geometries and ionospheric scintillation may degrade the signal quality. In this respect, data affected by scintillation events were identified and used for the performance analysis. The assessment is carried out by comparing the HAS corrections with the International GNSS Service (IGS) precise products. Moreover, the retrieved HAS corrections are used to assess the Precise Point Positioning (PPP) performance.

Cold-active bacteriophages are bacterial viruses that infect and replicate at low temperatures (≤4 °C). Understanding remains limited of how cold-active phage–host systems sustain high viral abundance despite the persistently low temperatures in pelagic sediments in polar seas. In this study, two Pseudoalteromonas phages, ACA1 and ACA2, were isolated from sediment core samples of the continental shelf in the western Arctic Ocean. These phages exhibited successful propagation at a low temperature of 1 °C and displayed typical myovirus morphology with isometric icosahedral heads and contractile tails. The complete genome sequences of phages ACA1 and ACA2 were 36,825 bp and 36,826 bp in size, respectively, sharing almost the same gene content. These are temperate phages encoding lysogeny-related proteins such as anti-repressor, immunity repressor and integrase. The absence of cross-infection between the host strains, which were genomically distinct Pseudoalteromonas species, can likely be attributed to heavy divergence in the anti-receptor apparently mediated by an associated diversity-generating retroelement. HHpred searching identified genes for all of the structural components of a P2-like phage (family Peduoviridae), although the whole of the Peduoviridae family appeared to be divided between two anciently diverged tail modules. In contrast, Blast matching and whole genome tree analysis are dominated by a nonstructural gene module sharing high similarity with Pseudoalteromonas phage C5a (founder of genus Catalunyavirus). This study expands the knowledge of diversity of P2-like phages known to inhabit Peudoalteromonas and demonstrates their presence in the Arctic niche.

PurposeMissing data is a key methodological consideration in longitudinal studies of aging. We described missing data challenges and potential methodological solutions using a case example describing five-year frailty state transitions in a cohort of older adults.MethodsWe used longitudinal data from the National Health and Aging Trends Study, a nationally-representative cohort of Medicare beneficiaries. We assessed the five components of the Fried frailty phenotype and classified frailty based on their number of components (robust: 0, prefrail: 1-2, frail: 3-5). One-, two-, and five-year frailty state transitions were defined as movements between frailty states or death. Missing frailty components were imputed using hot deck imputation. Inverse probability weights were used to account for potentially informative loss-to-follow-up. We conducted scenario analyses to test a range of assumptions related to missing data.ResultsMissing data were common for frailty components measured using physical assessments (walking speed, grip strength). At five years, 36% of individuals were lost-to-follow-up, differentially with respect to baseline frailty status. Assumptions for missing data mechanisms impacted inference regarding individuals improving or worsening in frailty.ConclusionsMissing data and loss-to-follow-up are common in longitudinal studies of aging. Robust epidemiologic methods can improve the rigor and interpretability of aging-related research.

Background/Aims: Few studies have investigated terminal ileal lesions and their prognostic value in patients with ulcerative colitis (UC). We evaluated the clinical significance of these lesions as a prognostic factor in patients with UC who were in clinical remission. Methods: We retrospectively selected 567 of 4,066 colonoscopy reports that included positive findings from orificial observations of the terminal ileum (TI) and appendix in patients with UC. We finally recruited patients who were in clinical remission (n=204). We compared the clinical courses, including relapse and other prognostic parameters associated with UC, between the groups. Results: The baseline patient characteristics were not significantly different between patients with (n=69, TI+ group) and without TI lesions (n=135, TI– group), although there were more never-smokers in the TI+ group (n=57 [82.6%] in the TI+ group; n=86 [63.7%] in the TI– group; p=0.005). Of note, appendiceal orifice inflammation (AOI) was less frequently found in the TI+ group (14.5%) than in the TI– group (71.9%, p

The incidence and prevalence rates of inflammatory bowel disease (IBD) have been increasing in East Asian countries over the past few decades. Accordingly, the general understanding and awareness of IBD among healthcare professionals has increased considerably in this region. This increase is ultimately associated with the evolving focus of IBD clinicians devoted to comprehensive patient care, especially in establishing IBD clinics/centers capable of providing multidisciplinary counseling. Comprehensive IBD care at IBD clinics/centers usually includes surgical and medication decision-making, transition from pediatric to adult clinics, care of extraintestinal manifestations, care of infectious diseases in patients undergoing immunomodulatory or biologic therapies, and nutritional, psychosocial, socioeconomic, and pharmacological care. Team members comprise specialists from various departments related to IBD and can be divided into core and ad hoc members. Usually, the scope of work in IBD clinics/centers involves patient care, patient outreach, and system management. Considering the environmental changes in IBD treatment, it is necessary to perform comprehensive IBD patient care in the form of a program based on competencies, rather than simply following the organization of previous IBD centers. The present review summarizes recent trends in IBD patient care and offers perspectives regarding IBD center management.

A randomized phase 2 clinical trial has recently shown no benefit of the combination eribulin and pembrolizumab over pembrolizumab alone in HR + metastatic breast cancer patients (NCT03051659). Here, the authors are reporting the final OS data and biomarker analyses on a subset of samples to analyze molecular correlates

MicroRNA transcriptomes from fresh tumors and the adjacent normal tissues were profiled in 10 Korean patients diagnosed with lung adenocarcinoma using a next-generation sequencing (NGS) technique called miRNA-seq. The sequencing quality was assessed using FastQC, and low-quality or adapter-contaminated portions of the reads were removed using Trim Galore. Quality-assured reads were analyzed using miRDeep2 and Bowtie. The abundance of known miRNAs was estimated using the reads per million (RPM) normalization method. Subsequently, using DESeq2 and Wx, we identified differentially expressed miRNAs and potential miRNA biomarkers for lung adenocarcinoma tissues compared to adjacent normal tissues, respectively. We defined reliable miRNA biomarkers for lung adenocarcinoma as those detected by both methods. The miRNA-seq data are available in the Gene Expression Omnibus (GEO) database under accession number GSE196633, and all processed data can be accessed via the Mendeley data website.

Particulate matter (PM) is the most dangerous air pollutant that adversely affects health. Increasing PM in urban areas is a big problem that must be solved. This study analyzed the amount of PM that accumulated on plant leaves, as well as the leaf traits that contribute to PM accumulation, to determine the plant’s ability to accumulate PM and the impact of PM on the plants. Scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) analysis were used to quantitatively assess metal concentrations in the particles that had accumulated on the leaf samples. Eight common plant species that grow on the roadside were used to analyze leaf traits using leaf samples. Specific leaf areas (SLA), leaf extract pH (pH), relative leaf water content (RWC), chlorophyll (Chl), and carotenoids were analyzed. PM accumulation and leaf traits varied among plant species, and Parthenocissus tricuspidata showed the highest PM accumulation on its leaf surface. The leaf’s elemental composition included C, O, Ca, K, Mg, S, P, Al, Si, Na, Cl, and Fe. Among these elements, Ca, K, and Cl made up a relatively large percentage. Fe was only detected in the leaves of Pachysandra terminalis and P. tricuspidata, while C and O were excluded as they are not relevant in determining PM metal content. Plants not only accumulate PM but also heavy metals from the atmosphere. This study found that plants with highly effective PM accumulation, such as P. tricuspidate, should be considered for optimizing the benefits of plants in improving air quality.

Low-dose radiation refers to exposure to ionizing radiation at levels that are generally considered safe and not expected to cause immediate health effects. However, the effects of low-dose radiation are still not fully understood, and research in this area is ongoing. In this study, we investigated the alterations in gene expression profiles of human aortic endothelial cells (HAECs) and diabetic human aortic endothelial cells (T2D-HAECs) derived from patients with type 2 diabetes. To this end, we used RNA-seq to profile the transcriptomes of cells exposed to varying doses of low-dose radiation (0.1 Gy, 0.5 Gy, and 2.0 Gy) and compared them to a control group with no radiation exposure. Differentially expressed genes and enriched pathways were identified using the DESeq2 and gene set enrichment analysis (GSEA) methods, respectively. The data generated in this study are publicly available through the gene expression omnibus (GEO) database with the accession number GSE228572. This study provides a valuable resource for examining the effects of low-dose radiation on HAECs and T2D-HAECs, thereby contributing to a better understanding of the potential human health risks associated with low-dose radiation exposure.

Abstract Intestinal Behçet’s disease (BD) and Crohn’s disease (CD) present similar manifestations, but there are no specific diagnostic tests to differentiate them. We used a proteomic approach to discover novel diagnostic biomarkers specific to intestinal BD. Colon mucosa tissue samples were obtained from patients with intestinal BD or CD using colonoscopy-guided biopsy of the affected bowel. Peptides from seven intestinal BD and seven CD patients were extracted and labeled using tandem mass tag (TMT) reagents. The labeled peptides were identified and quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS). The proteins were further validated using immunohistochemical (IHC) analysis with tissue samples and an ELISA test with serum samples from 20 intestinal BD and 20 CD patients. Using TMT/LC–MS/MS-based proteomic quantification, we identified 39 proteins differentially expressed between intestinal BD and CD. Beta-2 glycoprotein 1 (APOH) and maltase-glucoamylase (MGAM) showed higher intensity in the IHC staining of intestinal BD tissues than in CD tissues. The serum MGAM level was higher in intestinal BD patients. Proteomic analysis revealed that some proteins were differentially expressed in patients with intestinal BD compared with those with CD. Differential MGAM expression in intestinal BD suggests its role as a potential novel diagnostic biomarker.