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Abstract Background Pancreatic cancer is anatomically divided into pancreatic head and body/tail cancers, and some studies have reported differences in prognosis. However, whether this discrepancy is induced from the difference of tumor biology is hotly debated. Therefore, we aimed to evaluate the differences in clinical outcomes and tumor biology depending on the tumor location. Methods In this retrospective cohort study, we identified 800 patients with pancreatic ductal adenocarcinoma who had undergone upfront curative-intent surgery. Cox regression analysis was performed to explore the prognostic impact of the tumor location. Among them, 153 patients with sufficient tumor tissue and blood samples who provided informed consent for next-generation sequencing were selected as the cohort for genomic analysis. Results Out of the 800 patients, 500 (62.5%) had pancreatic head cancer, and 300 (37.5%) had body/tail cancer. Tumor location in the body/tail of the pancreas was not identified as a significant predictor of survival outcomes compared to that in the head in multivariate analysis (hazard ratio, 0.94; 95% confidence interval, 0.77–1.14; P = 0.511). Additionally, in the genomic analyses of 153 patients, there were no significant differences in mutational landscapes, distribution of subtypes based on transcriptomic profiling, and estimated infiltration levels of various immune cells between pancreatic head and body/tail cancers. Conclusions We could not find differences in prognosis and tumor biology depending on tumor location in pancreatic ductal adenocarcinoma. Discrepancies in prognosis may represent a combination of lead time, selection bias, and clinical differences, including the surgical burden between tumor sites.

Background Administration of pancreatic endoplasmic reticulum kinase inhibitor (PERKi) improved insulin secretion and hyperglycemia in obese diabetic mice. In this study, autophagic balance was studied whether to mediate it. Methods Human islets were isolated from living patients without diabetes. PERKi GSK2606414 effects were evaluated in the islets under glucolipotoxicity by palmitate. Islet insulin contents and secretion were measured. Autophagic flux was assessed by microtubule associated protein 1 light chain 3 (LC3) conversion, a red fluorescent protein (RFP)-green fluorescent protein (GFP)- LC3 tandem assay, and P62 levels. For mechanical analyses, autophagy was suppressed using 3-methyladenine in mouse islets. Small interfering RNA for an autophagy-related gene autophagy related 7 (Atg7) was transfected to interfere autophagy. Results PERKi administration to mice decreased diabetes-induced P62 levels in the islets. Glucolipotoxicity significantly increased PERK phosphorylation by 70% and decreased insulin contents by 50% in human islets, and addition of PERKi (40 to 80 nM) recovered both. PERKi also enhanced glucose-stimulated insulin secretion (6-fold). PERKi up-regulated LC3 conversion suppressed by glucolipotoxicity, and down-regulated P62 contents without changes in P62 transcription, indicating enhanced autophagic flux. Increased autophagosome-lysosome fusion by PERKi was visualized in mouse islets, where PERKi enhanced Atg7 bound to LC3. Suppression of Atg7 eliminated PERKi-induced insulin contents and secretion. Conclusion This study provided functional changes of human islets with regard to autophagy under glucolipotoxicity, and suggested modulation of autophagy as an anti-diabetic mechanism of PERKi.

Abstract For enhanced security in hardware‐based security devices, it is essential to extract various independent characteristics from a single device to generate multiple keys based on specific values. Additionally, the secure destruction of authentication information is crucial for the integrity of the data. Doped amorphous indium gallium zinc oxide (a‐IGZO) thin‐film transistors (TFTs) using poly(vinylidene fluoride‐co‐hexafluoropropylene) (PVDF‐HFP) induce a dipole doping effect through a phase‐transition process, creating physically unclonable function (PUF) devices for secure user information protection. The PUF security key, generated at VGS = 20 V in a 20 × 10 grid, demonstrates uniformity of 42% and inter‐Hamming distance (inter‐HD) of 49.79% in the β‐phase of PVDF‐HFP. However, in the γ‐phase, the uniformity drops to 22.5%, and inter‐HD decreases to 35.74%, indicating potential security key destruction during the phase transition. To enhance security, a multi‐factor authentication (MFA) system is integrated, utilizing five security keys extracted from various TFT parameters. The security keys from turn‐on voltage (VON), VGS = 20 V, VGS = 30 V, mobility, and threshold voltage (Vth) exhibit near‐ideal uniformities and inter‐HDs, with the highest values of 58% and 51.68%, respectively. The dual security system, combining phase transition and MFA, establishes a robust protection mechanism for privacy‐sensitive user information.

Abstract Background Bladder cancer (BLCA) research in Koreans is still lacking, especially in focusing on the prediction of BLCA. The current study aimed to discover metabolic signatures related to BLCA onset and confirm its potential as a biomarker. Methods We designed two nested case-control studies using Korean Cancer Prevention Study (KCPS)-II. Only males aged 35–69 were randomly selected and divided into two sets by recruitment organizations [set 1, BLCA (n = 35) vs. control (n = 35); set 2, BLCA (n = 31) vs. control (n = 31)]. Baseline serum samples were analyzed by non-targeted metabolomics profiling, and OPLS-DA and network analysis were performed. Calculated genetic risk score (GRS) for BLCA from all KCPS participants was utilized for interpreting metabolomics data. Results Critical metabolic signatures shown in the BLCA group were dysregulation of lysine metabolism and tryptophan-indole metabolism. Furthermore, the prediction model consisting of metabolites (lysine, tryptophan, indole, indoleacrylic acid, and indoleacetaldehyde) reflecting these metabolic signatures showed mighty BLCA predictive power (AUC: 0.959 [0.929–0.989]). The results of metabolic differences between GRS-high and GRS-low groups in BLCA indicated that the pathogenesis of BLCA is associated with a genetic predisposition. Besides, the predictive ability for BLCA on the model using GRS and five significant metabolites was powerful (AUC: 0.990 [0.980–1.000]). Conclusion Metabolic signatures shown in the present research may be closely associated with BLCA pathogenesis. Metabolites involved in these could be predictive biomarkers for BLCA. It could be utilized for early diagnosis, prognostic diagnosis, and therapeutic targets for BLCA.

Abstract Background Pancreatic cancer is a lethal disease with a high mortality rate. The difficulty of early diagnosis is one of its primary causes. Therefore, we aimed to discover non-invasive biomarkers that facilitate the early diagnosis of pancreatic cancer risk. Methods The study subjects were randomly selected from the Korean Cancer Prevention Study-II and matched by age, sex, and blood collection point [pancreatic cancer incidence (n = 128) vs. control (n = 256)]. The baseline serum samples were analyzed by non-targeted metabolomics, and XGBoost was used to select significant metabolites related to pancreatic cancer incidence. Genomewide association study for the selected metabolites discovered valuable single nucleotide polymorphisms (SNPs). Moderation and mediation analysis were conducted to explore the variables related to pancreatic cancer risk. Results Eleven discriminant metabolites were selected by applying a cut-off of 4.0 in XGBoost. Five SNP presented significance in metabolite-GWAS (p ≤ 5 × 10–6) and logistic regression analysis. Among them, the pair metabolite of rs2370981, rs55870181, and rs72805402 displayed a different network pattern with clinical/biochemical indicators on comparison with allelic carrier and non-carrier. In addition, we demonstrated the indirect effect of rs59519100 on pancreatic cancer risk mediated by γ-glutamyl tyrosine, which affects the smoking status. The predictive ability for pancreatic cancer on the model using five SNPs and four pair metabolites with the conventional risk factors was the highest (AUC: 0.738 [0.661–0.815]). Conclusions Signatures involving metabolites and SNPs discovered in the present research may be closely associated with the pathogenesis of pancreatic cancer and for use as predictive biomarkers allowing early pancreatic cancer diagnosis and therapy.

Oxygen vacancies are a major factor that controls the electrical characteristics of the amorphous indium-gallium-zinc oxide transistor (a-IGZO TFT). Oxygen vacancies are affected by the composition ratio of the a-IGZO target and the injected oxygen flow rate. In this study, we fabricated three types of a-IGZO TFTs with different oxygen flow rates and then investigated changes in electrical characteristics. Atomic force microscopy (AFM) was performed to analyze the surface morphology of the a-IGZO films according to the oxygen gas rate. Furthermore, X-ray photoelectron spectroscopy (XPS) analysis was performed to confirm changes in oxygen vacancies of a-IGZO films. The optimized a-IGZO TFT has enhanced electrical characteristics such as carrier mobility (μ) of 12.3 cm2/V·s, on/off ratio of 1.25 × 1010 A/A, subthreshold swing (S.S.) of 3.7 V/dec, and turn-on voltage (Vto) of −3 V. As a result, the optimized a-IGZO TFT has improved electrical characteristics with oxygen vacancies having the highest conductivity.

Abstract Introduction We aimed to find a novel candidate gene related to the white blood cell (WBC) count in a Korean population. Since WBC count has been reported to have a relation to the risk of chronic diseases according to previous literature, WBC level prediction can be helpful for managing future risk of chronic disease development. In this aspect, a gene newly found in the present study is expected to be utilized as a tool for judging an individual's WBC level. Methods Based on the 153 study participants' genotype data produced by the Korean Chip. The mono‐adenosine diphosphate ribosylhydrolase 2 (MACROD2) rs6110695 A>G polymorphism had a significant strong association with WBC count, thus, the MACROD2 gene emerged as a novel candidate gene for WBC count. To verify the effects of the single‐nucleotide polymorphisms on WBC count, the participants were grouped according to the rs6110695 AA and AG genotypes. Results WBC to apolipoprotein A‐I ratio, WBC count, granulocyte to lymphocyte ratio, monocyte to platelet ratio, and interferon‐γ level were significantly higher in the AG genotype group than in the AA genotype group. Through the receiver operating characteristic curve analysis, the rs6110695 AA and AG genotypes were discriminated by the optimal WBC count cutoff value of 5.450. As expected, the results in the participants having a WBC count over 5.450 were similar to the AG genotype group. Conclusions We revealed that the MACROD2 rs6110695 AG genotype has an association with increasing WBC count. Since, as previous literature described, WBC count is one of the main risk factors for chronic diseases, WBC count measurement in individuals with the rs6110695 AG genotype that was found in the present study may help manage future chronic disease risk.

Abstract Background Research elucidating the metabolic mechanisms that differentiate subtypes of obesity has been increasing. We aimed to investigate the effects of a 12-week dietary intervention on the metabolomic profiles of obese subjects. Methods Subjects followed a 12-week dietary restriction protocol consisting of a 300 kcal/day reduction in their usual caloric intake. Twenty-nine obese subjects were included and divided into two groups: the metabolic status maintenance group (n = 17, controls) and the metabolic status improvement group (n = 12, tests). We analyzed the somatometric and biochemical parameters and performed ultra-performance liquid chromatography-mass spectrometry analysis of the plasma metabolites. Results At 12 weeks, the fat percentage, whole fat area (WFA), subcutaneous fat area (SFA) at the L1 vertebra, and the levels of triglycerides, gamma-glutamyltransferase (gamma-GT), and leptin were markedly decreased in the metabolic status improvement group, while the level of high-density lipoprotein cholesterol increased compared with that in the metabolic status maintenance group. Metabolomic profiling at 12 weeks showed substantial differences in 4-aminobutyraldehyde (p = 0.005) and 4’-apo-β-carotenal (p = 0.024) between the two groups. Furthermore, an AUC value of 0.89 was obtained for the following seven featured biomarkers: triglycerides, gamma-GT, leptin, fat percentage, WFA, and SFA at the L1 vertebra, and 4-aminobutyraldehyde. Conclusions We demonstrated that 4-aminobutyraldehyde and related regional fat distribution parameters were strongly associated with obesity according to metabolic status. Thus, these biomarkers are potentially valuable in confirming the efficacy of short-term interventions and predicting metabolic status in obese individuals. Trials registration: This study was registered at ClinicalTrials.gov under NCT03135132 (registered 1 May 2017—retrospectively registered).

Background/Aims: Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of first-line chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC. Methods: In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment. Results: For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOLFIRINOX (p

Gallbladder cancer incidence shows characteristic geographic patterns. Here the authors perform a genomic analysis of gallbladder cancers in patients from countries with high incidence (South Korea, India and Chile) and identify ELF3 and other significantly mutated genes not previously associated with gallbladder cancer.

Background/Aims: We investigated chromosomal aberrations in patients with pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) by fluorescence in situ hybridization (FISH) to identify cytogenetic changes and molecular markers that may be useful for preoperative diagnosis. Methods: Tissue samples from 48 PDAC and 17 IPMN patients were investigated by FISH analysis using probes targeting chromosomes 7q, 17p, 18q, 20q, and 21q and the pericentromeric region of chromosome 18 (CEP18). Results: The PDAC samples harbored 17p deletion (95.8%), 18q deletion (83.3%), CEP18 deletion (81.2%), 20q gain (81.2%), 21q deletion (77.1%), and 7q gain (70.8%). The IPMN samples had 17p deletion (94.1%), CEP18 deletion (94.1%), 21q deletion (70.6%), 18q deletion (58.8%), 20q gain (58.8%), and 7q gain (58.8%). A significant difference in CEP18 gain was identified between the PDAC and IPMN groups (p=0.029). Detection of 17p or 18q deletion had the highest diagnostic accuracy (80.0%) for PDAC. Conclusions: Chromosomal alterations were frequently identified in both PDAC and IPMN with similar patterns. CEP18 gain and 17p and 18q deletions might be involved in the later stages of PDAC tumorigenesis. Chromosome 17p and 18q deletions might be excellent diagnostic markers.

Large-scale product inspection is an important aspect in thin film industry to identify defects with a high precision. Although vision line scan camera (VLSC)-based inspection has been frequently implemented, it is limited to surface inspections. Therefore, to overcome the conventional drawbacks, there is a need to extend inspection capabilities to internal structures. Considering that VLSC systems have access to rich information, such as color and texture, high-resolution real-time multimodal optical synchronization between VLSC and dual spectral domain optical coherence tomography (SD-OCT) systems was developed with a laboratory customized in-built automated defect-tracking algorithm for optical thin films (OTFs). Distinguishable differences in the color and texture of the bezel area were precisely determined by the VLSC. Detailed OCT assessments were conducted to verify the detection of previously unobtainable border regions and micrometer-range sub-surface defects. To enhance the accuracy of the method, VLSC images were aided for the precise surface defect identification using OCT and the image acquisition, signal processing, image analysis, and classification of both techniques were simultaneously processed in real-time for industrial applicability. The results demonstrate that the proposed method is capable of detecting and enumerating total number of defects in OTF samples with exceptional resolution and in a cost-effective manner facilitating wide area inspection for OTF samples.

Abstract Certain tumors such as pancreatic ductal adenocarcinoma (PDAC) are known to contain a variety of hydrolytic enzymes including RNases and proteases that may lead to degradation of RNA and proteins during sample processing. For such tumor tissues with RNA instability, RNAlater containing a high concentration of quaternary ammonium sulfates that denature RNA-hydrolyzing enzymes is often used to protect RNAs from hydrolysis. Although a few studies have been carried out to determine the effect of RNAlater on DNA and RNA, whether RNAlater influences the proteome and phosphoproteome is largely unknown. In this study we carried out a systematic and comprehensive analysis of the effect of RNAlater on the proteome and phosphoproteome using high-resolution mass spectrometry. PDAC tissues from three patients were individually pulverized and the tissue powders of each patient were divided into two portions, one of which was incubated in RNAlater at 4 °C for 24 h (RNAlater tissue) while the other was kept at – 80 °C (frozen tissue). Comprehensive quantitative profiling experiments on the RNAlater tissues and the frozen tissues resulted in the identification of 99,136 distinct peptides of 8803 protein groups and 17,345 phosphopeptides of 16,436 phosphosites. The data exhibited no significant quantitative changes in both proteins and phosphorylation between the RNAlater tissues and the frozen tissue. In addition, the phosphoproteome data showed heterogeneously activated pathways among the three patients that were not altered by RNAlater. These results indicate that the tissue preservation method using RNAlater can be effectively used on PDAC tissues for proteogenomic studies where preservation of intact DNA, RNA and proteins is prerequisite. Data from this study are available via ProteomeXchange with the identifier PXD010710.

We aimed to use a genetic risk score (GRS) constructed with prediabetes and type 2 diabetes-related single nucleotide polymorphisms (SNPs) and an oxidative stress score (OSS) to construct an early-prediction model for prediabetes and type 2 diabetes (T2DM) incidence in a Korean population. The study population included 549 prediabetes and T2DM patients and 1036 normal subjects. The GRS was constructed using six prediabetes and T2DM-related SNPs, and the OSS was composed of three recognized oxidative stress biomarkers. Among the nine SNPs, six showed significant associations with the incidence of prediabetes and T2DM. The GRS was profoundly associated with increased prediabetes and T2DM (OR = 1.946) compared with individual SNPs after adjusting for age, sex, and BMI. Each of the three oxidative stress biomarkers was markedly higher in the prediabetes and T2DM group than in the normal group, and the OSS was significantly associated with increased prediabetes and T2DM (OR = 2.270). When BMI was introduced to the model with the OSS and GRS, the area under the ROC curve improved (from 69.3% to 70.5%). We found that the prediction model composed of the OSS, GRS, and BMI showed a significant prediction ability for the incidence of prediabetes and T2DM.

Background: Non-randomized studies have investigated multi-agent gemcitabine-based neo-adjuvant therapies (GEM-NAT) in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC). Treatment sequencing and specific elements of neoadjuvant treatment are still under investigation. The present meta-analysis aims to assess the effectiveness of GEM-NAT on overall survival (OS) in BR-PDAC.Patients and Methods: A meta-analysis of individual participant data (IPD) on GEM-NAT for BR-PDAC were performed. The primary outcome was OS after treatment with GEM-based chemotherapy. In the Individual Patient Data analysis data were reappraised and confirmed as BR-PDAC on provided radiological data.Results: Six studies investigating GEM-NAT were included in the IPD metanalysis. The IPD metanalysis was conducted on 271 patients who received GEM-NAT. Pooled median patient-level OS was 22.2 months (95%CI 19.1–25.2). R0 rates ranged between 81 and 95% (I2 = 0%, p = 0.64), respectively. Median OS was 27.8 months (95%CI 23.9–31.6) in the patients who received NAT-GEM followed by resection compared to 15.4 months (95%CI 12.3–18.4) for NAT-GEM without resection and 13.0 months (95%CI 7.4–18.5) in the group of patients who received upfront surgery (p < 0.0001). R0 rates ranged between 81 and 95% (I2 = 0%, p = 0.64), respectively. Overall survival in the R0 group was 29.3 months (95% CI 24.3–34.2) vs. 16.2 months (95% CI 7·9–24.5) in the R1 group (p = 0·001).Conclusions: The present study is the first meta-analysis combining IPD from a number of international centers with BR-PDAC in a cohort that underwent multi-agent gemcitabine neoadjuvant therapy (GEM-NAT) before surgery. GEM-NAT followed by surgical resection improve survival and R0 resection in BR-PDAC. Also, GEM-NAT may result in a good palliative option in non-resected patients because of progressive disease after neoadjuvant treatment. Results from randomized controlled trials (RCTs) are awaited to validate these findings.

Abstract Background The application of advanced imaging technologies for identifying pancreatic cysts has become widespread. However, accurately differentiating between low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive intraductal papillary mucinous neoplasms (IPMNs) remains a diagnostic challenge with current biomarkers, necessitating the development of novel biomarkers that can distinguish IPMN malignancy. Methods Cyst fluid samples were collected from nine IPMN patients (3 LGD, 3 HGD, and 3 invasive IPMN) during their pancreatectomies. An integrated proteomics approach that combines filter-aided sample preparation, stage tip-based high-pH fractionation, and high-resolution MS was applied to acquire in-depth proteomic data of pancreatic cyst fluid and discover marker candidates for IPMN malignancy. Biological processes of differentially expressed proteins that are related to pancreatic cysts and aggressive malignancy were analyzed using bioinformatics tools such as gene ontology analysis and Ingenuity pathway analysis. In order to confirm the validity of the marker candidates, 19 cyst fluid samples were analyzed by western blot. Results A dataset of 2992 proteins was constructed from pancreatic cyst fluid samples. A subsequent analysis found 2963 identified proteins in individual samples, 2837 of which were quantifiable. Differentially expressed proteins between histological grades of IPMN were associated with pancreatic diseases and malignancy according to ingenuity pathway analysis. Eighteen biomarker candidates that were differentially expressed across IPMN histological grades were discovered—7 DEPs that were upregulated and 11 that were downregulated in more malignant grades. HOOK1 and PTPN6 were validated by western blot in an independent cohort, the results of which were consistent with our proteomic data. Conclusions This study demonstrates that novel biomarker candidates for IPMN malignancy can be discovered through proteomic analysis of pancreatic cyst fluid.

We aimed to investigate whether retinal and retinoic acid (RA), which are newly discovered biomarkers from our previous research, reliably predict type 2 diabetes mellitus (T2DM) development in subjects with impaired fasting glucose (IFG). Among the Korean Cancer Prevention Study (KCPS)-II cohort, subjects were selected and matched by age and sex (IFG-IFG group, n = 100 vs. IFG-DM group, n = 100) for study 1. For real-world validation of two biomarkers (study 2), other participants in the KCPS-II cohort who had IFG at baseline (n = 500) were selected. Targeted LC/MS was used to analyze the baseline serum samples; retinal and RA levels were quantified. In study 1, we revealed that both biomarkers were significantly decreased in the IFG-DM group (retinal, p = 0.017; RA, p < 0.001). The obese subjects in the IFG-DM group showed markedly lower retinal (p = 0.030) and RA (p = 0.003) levels than those in the IFG-IFG group. In study 2, the results for the two metabolites tended to be similar to those of study 1, but no significant difference was observed. Notably, the predictive ability for T2DM was enhanced when the metabolites were added to conventional risk factors for T2DM in both studies (study 1, AUC 0.682 → 0.775; study 2, AUC 0.734 → 0.786). The results suggest that retinal- and RA-related metabolic pathways are altered before the onset of T2DM.

Tumor-infiltrating lymphocytes (TILs), found in patients with advanced pancreatic ductal adenocarcinoma (PDAC), are shown to correlate with overall survival (OS) rate. Although majority of TILs consist of CD8+/CD4+ T cells, the presence of NK cells and their role in the pathogenesis of PDAC remains elusive. We performed comprehensive analyses of TIL, PBMC, and autologous tumor cells from 80 enrolled resectable PDAC patients to comprehend the NK cell defects within PDAC. Extremely low frequencies of NK cells (

Novel biomarkers for early diagnosis of pancreatic cancer (PC) are necessary to improve prognosis. We aimed to discover candidate biomarkers by identifying compositional differences of microbiome between patients with PC (n = 38) and healthy controls (n = 52), using microbial extracellular vesicles (EVs) acquired from blood samples. Composition analysis was performed using 16S rRNA gene analysis and bacteria-derived EVs. Statistically significant differences in microbial compositions were used to construct PC prediction models after propensity score matching analysis to reduce other possible biases. Between-group differences in microbial compositions were identified at the phylum and genus levels. At the phylum level, three species (Verrucomicrobia, Deferribacteres, and Bacteroidetes) were more abundant and one species (Actinobacteria) was less abundant in PC patients. At the genus level, four species (Stenotrophomonas, Sphingomonas, Propionibacterium, and Corynebacterium) were less abundant and six species (Ruminococcaceae UCG-014, Lachnospiraceae NK4A136 group, Akkermansia, Turicibacter, Ruminiclostridium, and Lachnospiraceae UCG-001) were more abundant in PC patients. Using the best combination of these microbiome markers, we constructed a PC prediction model that yielded a high area under the receiver operating characteristic curve (0.966 and 1.000, at the phylum and genus level, respectively). These microbiome markers, which altered microbial compositions, are therefore candidate biomarkers for early diagnosis of PC.

Depth-visualizing sensitivity can be degraded due to imperfect optical alignment and non-equidistant distribution of optical signals in the pixel array, which requires a measurement of the re-sampling process. To enhance this depth-visualizing sensitivity, reference and sample arm-channeled spectra corresponding to different depths using mirrors were obtained to calibrate the spectrum sampling prior to Fourier transformation. During the process, eight interferogram patterns corresponding to point spread function (PSF) signals at eight optical path length differences were acquired. To calibrate the spectrum, generated intensity points of the original interferogram were re-indexed towards a maximum intensity range, and these interferogram re-indexing points were employed to generate a new lookup table. The entire software-based process consists of eight consecutive steps. Experimental results revealed that the proposed method can achieve images with a high depth-visualizing sensitivity. Furthermore, the results validate the proposed method as a rapidly performable spectral calibration technique, and the real-time images acquired using our technique confirm the simplicity and applicability of the method to existing optical coherence tomography (OCT) systems. The sensitivity roll-off prior to the spectral calibration was measured as 28 dB and it was halved after the calibration process.

This article examines the relationship between changes in liver enzymes and hepatic fat and their potential connection to cardiovascular disease (CVD). The study involved 900 healthy subjects, with 79 individuals showing slightly elevated alanine aminotransferase (ALT) levels after three years. The results indicated that elevated ALT levels were associated with higher levels of other CVD risk indicators, such as aspartate aminotransferase (AST), gamma-glutamyltransferase (¿-GT), high sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, oxidized low-density lipoprotein (ox-LDL), urinary 8-epi-prostaglandin F2¿ (8-epi-PGF2¿), and brachial-ankle pulse wave velocity (ba-PWV). The study suggests that increased Lp-PLA2 activity and other CVD risk factors may contribute to chronic low-grade inflammation. The study also found that elevated liver enzymes and increased Lp-PLA2 activity contribute to systemic inflammation in non-alcoholic fatty liver disease (NAFLD), and that both ALT levels and Lp-PLA2 activity could serve as valuable non-invasive markers for detecting the advanced status of NAFLD. However, the study had limitations in terms of sample size and correlation analysis, and further research is needed to confirm these findings. [Extracted from the article]

Background: Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers. Methods: In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test. Results: Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501). Conclusion: Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice. [ABSTRACT FROM AUTHOR]

Background: Major vessel invasion is an important factor for determining the surgical approach and long-term prognosis for patients with pancreatic head cancer. However, clinical implications of vessel invasion have seldom been reported in pancreatic body or tail cancer. This study aimed to evaluate the clinical relevance of splenic vessel invasion with pancreatic body or tail cancer compared with no invasion and investigate prognostic factors. Methods: This study enrolled patients who underwent upfront distal pancreatectomy from 2005 to 2018. The circular degree of splenic vessel invasion was investigated and categorized into three groups (group 1, no invasion; group 2, 0-180°; group 3, 180° or more). Clinicopathological variables and perioperative and survival outcomes were evaluated, and multivariable Cox proportional analysis was performed to evaluate prognostic factors. Results: Among 249 enrolled patients, tumour size was larger in patients with splenic vessel invasion (3.9 versus 2.9cm, P=0.001), but the number of metastatic lymph nodes was comparable to that in patients with no vessel invasion (1.7 versus 1.4, P=0.241). The 5-year overall survival rates differed significantly between the three groups (group 1, 38.4 per cent; group 2, 16.8 per cent; group 3, 9.7 per cent, P<0.001). Patients with both splenic artery and vein invasion had lower 5-year overall survival rates than those with one vessel (7.5 versus 20.2 per cent, P=0.021). Cox proportional analysis revealed adjuvant treatment, R0 resection and splenic artery invasion as independent prognostic factors for adverse outcomes in pancreatic body or tail cancer. Conclusion: Splenic vessel invasion was associated with higher recurrence and lower overall survival in pancreatic body or tail cancers suggesting a need for a neoadjuvant approach. [ABSTRACT FROM AUTHOR]

Objective: This study was performed to determine whether neoadjuvant treatment increases survival in patients with BRPC. Summary Background Data: Despite many promising retrospective data on the effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC), no high-level evidence exists to support the role of such treatment. Methods: This phase 2/3 multicenter randomized controlled trial was designed to enroll 110 patients with BRPC who were randomly assigned to gemcitabine-based neoadjuvant chemoradiation treatment (54 Gray external beam radiation) followed by surgery or upfront surgery followed by chemoradiation treatment from four large-volume centers in Korea. The primary endpoint was the 2-year survival rate (2-YSR). Interim analysis was planned at the time of 50% case enrollment. Results: After excluding the patients who withdrew consent (n = 8) from the 58 enrolled patients, 27 patients were allocated to neoadjuvant treatment and 23 to upfront surgery groups. The overall 2-YSR was 34.0% with a median survival of 16 months. In the intention-to-treat analysis, the 2-YSR and median survival were significantly better in the neoadjuvant chemoradiation than the upfront surgery group [40.7%, 21 months vs 26.1%, 12 months, hazard ratio 1.495 (95% confidence interval 0.66-3.36), P = 0.028]. R0 resection rate was also significantly higher in the neoadjuvant chemoradiation group than upfront surgery (n = 14, 51.8% vs n = 6, 26.1%, P = 0.004). The safety monitoring committee decided on early termination of the study on the basis of the statistical significance of neoadjuvant treatment efficacy. Conclusion: This is the first prospective randomized controlled trial on the oncological benefits of neoadjuvant treatment in BRPC. Compared to upfront surgery, neoadjuvant chemoradiation provides oncological benefits in patients with BRPC. [ABSTRACT FROM AUTHOR]

Objective : Recently, regenerative therapies have been used in clinical trials (heart, cartilage, skeletal). We don't make use of these treatments to spinal cord injury (SCI) patients yet, but regenerative therapies are rising interest in recent study about SCI. Neural precursor/stem cell (NPSC) proliferation is a significant event in functional recovery of the central nervous system (CNS). However, brain NPSCs and spinal cord NPSCs (SC-NPSCs) have many differences including gene expression and proliferation. The purpose of this study was to investigate the influence of neural growth factor (NGF) on the proliferation of SC-NPSCs. Methods : NPSCs (2×104) were suspended in 100 µL of neurobasal medium containing NGF-7S (Sigma-Aldrich) and cultured in a 96-well plate for 12 days. NPSC proliferation was analyzed five times for either concentration of NGF (0.02 and 2 ng/mL). Sixteen rats after SCI were randomly allocated into two groups. In group 1 (SCI-vehicle group, n=8), animals received 1.0 mL of the saline vehicle solution. In group 2 (SCI-NGF group, n=8), the animals received single doses of NGF (Sigma-Aldrich). A dose of 0.02 ng/mL of NGF or normal saline as a vehicle control was intra-thecally injected daily at 24 hour intervals for 7 days. For Immunohistochemistry analysis, rats were sacrificed after one week and the spinal cords were obtained. Results : The elevation of cell proliferation with 0.02 ng/mL NGF was significant (p<0.05) but was not significant for 2 ng/mL NGF. The optical density was increased in the NGF 0.02 ng/mL group compared to the control group and NGF 2 ng/mL groups. The density of nestin in the SCI-NGF group was significantly increased over the SCI-vehicle group (p<0.05). High power microscopy revealed that the density of nestin in the SCI-NGF group was significantly increased over the SCI-vehicle group. Conclusion : SC-NPSC proliferation is an important pathway in the functional recovery of SCI. NGF enhances SC-NPSC proliferation in vitro and in vivo. NGF may be a useful option for treatment of SCI patients pending further studies to verify the clinical applicability. [ABSTRACT FROM AUTHOR]

We report the case of 57-year-old woman diagnosed with Charcot-Marie-Tooth (CMT) disease and lumbar disk herniation (LDH). She had left leg weakness and foot numbness, foot deformity (muscle atrophy, high arch, and clawed toes). The lumbar spine MRI showed LDH at L4-5. Additionally, electrophysiology results were consistent with chronic peripheral motor-sensory polyneuropathy (axonopathy). In genetic testing, 17p11.2- p12 duplication/deletions characteristic of CMT disease were observed. We confirmed the patient's diagnosis as CMT disease and used conservative treatment. [ABSTRACT FROM AUTHOR]