Search

Background/Aims: Lymphoepithelioma-like carcinoma (LELC) is a rare subtype of gastric cancer. We aimed to identify the clinicopathological features and rate of lymph node metastasis (LNM) to investigate the feasibility of endoscopic submucosal dissection for early gastric LELC confined to the mucosa or submucosa.Methods: We compared the clinicopathological characteristics of 116 early gastric LELC patients and 5,753 early gastric well- or moderately differentiated (WD or MD) tubular adenocarcinoma patients treated by gastrectomy.Results: Compared to WD or MD early gastric cancer (EGC) patients, early LELC patients were younger and had a higher prevalence of proximally located tumors. Despite more frequent deep submucosal invasion (86.2% vs 29.8%), lymphatic invasion was less frequent (6.0% vs 16.2%) in early LELC patients than in WD or MD EGC patients. Among tumors with deep submucosal invasion, the tumor size was smaller, lymphatic invasion was less frequent (6.0% vs 40.2%) and the rate of LNM was lower (10.0% vs 19.4%) in patients with LELC than in those with WD or MD EGC. The overall rate of LNM in early LELC patients was 8.6% (10/116). The risk of LNM in patients with mucosal, shallow submucosal invasive, or deep submucosal invasive LELC was 0% (0/6), 0% (0/10), and 10% (10/100), respectively.Conclusions: Early LELC is a distinct subtype of EGC with more frequent deep submucosal invasion but less lymphatic invasion and LNM than WD or MD EGCs. Endoscopic submucosal dissection may be considered curative for patients with early LELC confined to the mucosa or shallow submucosa, given its negligible rate of LNM.

Abstract Purpose By analyzing sentinel basin dissection (SBD) data from the SEntinel Node ORIented Tailored Approach (SENORITA) trial, we sought to determine the precise extent of the sentinel basin (SB) without a tracer. Materials and methods This study investigated SB length in patients (n = 25) who underwent laparoscopic SBD for early gastric cancer (EGC) in the SENORITA trial. SB length along the greater curvature (GC) and lesser curvature (LC) was measured intraoperatively before performing SBD. Results In all 25 cases, along the LC of the stomach, the lengths of the SB were 3.7 cm [2.0–5.0] (median [min–max]) proximally and 3.0 cm [2.3–5.5] distally; along the GC side, the lengths of the SB were 6.8 cm [3.5–11.0] proximally and 7.0 cm [3.8–9.5] distally from the tumors. The SB length at the GC or LC side was not significantly different between subgroups categorized by tumor depth, size, and longitudinal location. When tumors were located at the anterior wall of the stomach, the length of the proximal SB (10.0 cm [9.0–11.0]) at the GC side was the longest. In cases with several sentinel lymph nodes (SLNs), the lengths of the SB at the GC side were significantly longer than those with fewer SLNs. However, the lengths of the SB were similar on the LC side regardless of the number of SLNs. Conclusions This pilot study had some limitations of a small number of enrolled patients, the lack of research on the specific station of SLNs, and the inaccurate indication for sentinel node navigation surgery (SNNS) without tracer. Nevertheless, the present study which reported the extents of SBs might be the first step towards simplifying procedures in laparoscopic SNNS for stomach preservation in EGC.

Purpose Splenectomy for patients with remnant gastric cancer has been controversial. The purpose of this study is to identify the impact of splenectomy in the treatment of remnant gastric cancer. Methods We retrospectively analyzed 285 patients with remnant gastric cancer who underwent completion total gastrectomy with or without splenectomy in Samsung Medical Center, between September 1996 and December 2017. We used a 1:1 propensity score matching method for the analysis. The matching factors were age, sex, and pathologic stage. After the matching process, we compared the 5-year overall survival (OS) and the disease-free survival (DFS) between patients with and without splenectomy during completion total gastrectomy. Results The median duration of follow-up was 58.0 months (range, 0–132 months). After propensity score matching, there were no statistically significant differences between the splenectomy group (n=77) and no splenectomy group (n=77) in terms of clinicopathological features. The 5-year OS rate between the no splenectomy and splenectomy group were not significantly different. There was no significant difference between 5-year DFS of the matched groups. Multivariate analysis revealed that splenectomy is not a significant prognostic factor in terms of 5-year OS (no splenectomy vs. splenectomy; 61.5% vs. 60.2%, P=0.884) or DFS (74.9% vs. 69.8%, P=0.880). Conclusion Splenectomy has no impact on the OS and DFS in patients with remnant gastric cancer. Splenectomy during completion total gastrectomy may not be necessary.

BackgroundClinical benefits of the meso-jejunal lymph node (MJLN) dissection in remnant gastric cancer (RGC) patients have not been fully established. Hence, in this retrospective study, we evaluated the survival benefit of MJLN dissection and prognostic significance of MJLN metastasis in RGC patients who underwent gastrojejunostomy reconstruction after their initial gastrectomy.MethodsWe retrospectively reviewed 391 patients who underwent surgery for RGC at our institution between 1996 and 2019. Among them, 60 patients had MJLN dissection. The index value of the survival benefit gained by dissection of the MJLN was calculated by multiplying the frequency of metastasis at the MJLN station and the 5-year overall survival rate (5YOS) of patients with metastasis at that station. When the metastatic rate or 5YOS exceeded 10%, dissection was recommended. An index value of dissection greater than 1.0 was considered significant.ResultsTotal metastatic rate of MJLN was 35% (n = 21/60). Patients with MJLN metastasis had advanced pathologic stage compared to patients in the no-metastasis group (p < 0.001). In T2-T4 RGC patients, the metastatic rate of MJLN was 48.6% (n = 17/35), and their 5YOS was 28.4%. The calculated index value was 13.8. Also, patients with MJLN metastasis had a poorer overall survival than those without metastasis. MJLN metastasis was an independent prognostic factor of overall survival in multivariate analysis (HR 6.77, 95%CI 2.21-20.79, p = 0.001).ConclusionMJLN dissection should be considered for advanced RGC patients who underwent gastrojejunostomy after distal gastrectomy during their initial surgery according to the index value.

PurposeThe discrepancy between preoperative and final pathological staging has been a long-standing challenge for the application of clinical trials or appropriate treatment options. This study aimed to demonstrate the accuracy of preoperative staging of locally advanced gastric cancer using data from a large-scale randomized clinical trial.Materials and methodsOf the 1050 patients enrolled in the clinical trial, 26 were excluded due to withdrawal of consent (n = 20) or non-surgery (n = 6). The clinical and pathological staging was compared. Risk factor analysis for underestimation was performed using univariate and multivariate analyses.ResultsRegarding T staging by computed tomography, accuracy rates were 74.48, 61.62, 58.56, and 85.16% for T1, T2, T3 and T4a, respectively. Multivariate analysis for underestimation of T staging revealed that younger age, ulcerative gross type, circular location, larger tumor size, and undifferentiated histology were independent risk factors. Regarding nodal status estimation, 54.9% of patients with clinical N0 disease were pathologic N0, and 36.4% of patients were revealed to have pathologic N0 among clinical node-positive patients. The percentage of metastasis involvement at the D1, D1+, and D2 lymph node stations significantly increased with the advanced clinical N stage. Among all patients, 29 (2.8%), including 26 with peritoneal seeding, exhibited distant metastases.ConclusionsEstimating the exact pathologic staging remains challenging. A thorough evaluation is mandatory before treatment selection or trial enrollment. Moreover, we need to set a sufficient case number when we design the clinical trial considering the stage migration.

Summary: The extracellular RNA communication consortium (ERCC) is an NIH-funded program aiming to promote the development of new technologies, resources, and knowledge about exRNAs and their carriers. After Phase 1 (2013–2018), Phase 2 of the program (ERCC2, 2019–2023) aims to fill critical gaps in knowledge and technology to enable rigorous and reproducible methods for separation and characterization of both bulk populations of exRNA carriers and single EVs. ERCC2 investigators are also developing new bioinformatic pipelines to promote data integration through the exRNA atlas database. ERCC2 has established several Working Groups (Resource Sharing, Reagent Development, Data Analysis and Coordination, Technology Development, nomenclature, and Scientific Outreach) to promote collaboration between ERCC2 members and the broader scientific community. We expect that ERCC2’s current and future achievements will significantly improve our understanding of exRNA biology and the development of accurate and efficient exRNA-based diagnostic, prognostic, and theranostic biomarker assays.

Abstract This phase II clinical trial was performed to determine whether reduced-port laparoscopic surgery with complete D2 lymph node (LN) dissection for gastric cancer is a safe and feasible surgical technique. The prospectively enrolled 65 gastric cancer patients underwent reduced-port surgery (i.e., triple-incision totally laparoscopic distal gastrectomy [Duet TLDG] with D2 lymphadenectomy). Compliance rate was the primary outcome, which was defined as cases in which there was no more than one missing LN station during D2 LN dissection. The secondary outcomes were the numbers of dissected and retrieved LNs in each station and other short-term surgical outcomes and postoperative course. The compliance rate was 58.5%. The total number of retrieved LNs was 41 (range: 14–83 LNs). The most common station missing from LN retrieval was station no. 5 (35/65; 53.8%), followed by station no. 1 (24/65; 36.9%). The overall postoperative complication rate was 20.0% (13/65). One patient underwent surgical treatment for postoperative complications. There was no instances of mortality. Duet TLDG is an oncologically and technically safe surgical method of gastrectomy and D2 lymphadenectomy.

Abstract Background Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments. Methods To address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers. Results We identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors in ALK-mutant tumors, a significant association between PIK3CA-E542K mutation and AZD5363 response, and transcriptome expression of RNF11 as a potential predictor of response to gefitinib. Conclusions Collectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.

Introduction Patients who underwent curative gastrectomy for gastric cancer are regularly followed-up for the early detection of recurrence and postoperative symptom management. However, there is a lack of evidence with regard to proper surveillance intervals and diagnostic tools. This study aims to evaluate whether frequent surveillance tests have a survival benefit or improve the quality of life in patients who underwent curative resection for advanced gastric cancer.Methods and analysis The STOFOLUP trial is an investigator-initiated, parallel-assigned, multicentre randomised controlled trial involving 16 hospitals in the Republic of Korea. Patients (n=886) diagnosed with pathological stage II or III gastric adenocarcinoma will be randomised to either the 3-month or the 6-month group at a 1:1 ratio, stratified by trial site and tumour stage. Patients allocated to the 3-month group will undergo an abdominal CT scan every 3 months postoperatively and those allocated to the 6-month group will undergo CT every 6 months. The primary endpoint is 3-year overall survival and the secondary endpoints are quality of life, as assessed using KOrean QUality of life in Stomach cancer patients Study group-40, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the stomach cancer-specific module (STO22), and nutritional outcomes. Other survival data including data concerning 3-year disease-free survival, recurrence-free survival, gastric cancer-specific survival and postrecurrence survival will also be estimated. The first patient was enrolled on July 2021 and active patient enrolment is currently underway.Ethics and dissemination This study has been approved by the Institutional Review Board of eight of the participating hospitals (NCC 2021-0085, KBSMC2021-01-059, SMC 2021-01-140, KC21OEDE0082, 4-2021-0281, AJIRB-MED-INT-20-608, 2021-0515 and H-2102-093-1198). This study will be disseminated through peer-reviewed publications, national or international conferences.Trial registration number NCT04740346.

Purpose Preoperative endoscopic clipping is a popular method in identifying the location of tumors during total laparoscopic or robotic gastrectomy. We investigated the usefulness of additional intraoperative abdominal radiographs to identify the location of clips. Methods We retrospectively analyzed 331 patients with early gastric cancer who underwent endoscopic clipping before total laparoscopic or robotic gastrectomy between September 2012 and September 2018. Endoscopists applied two clips 1 cm from the proximal aspect of the upper margin of the tumor which was located above the angle of the stomach. We compared outcomes of patients who underwent preoperative abdominal radiographs only (group A) and those who underwent additional abdominal radiographs (group B). Results Of the total patients, 80 (24.2%) underwent additional intraoperative abdominal radiographs. The rates of positive frozen biopsy in the two groups were not significantly different (group A vs. group B: 2.8% vs. 3.8%, P=0.456). The additional resection rate was significantly higher in group B compared to group A (8.8% vs. 2.8%, P=0.048). The mean distance from the tumor was 3.3 cm (±2.4) in group A and 2.4 cm (±1.3) in group B (P

Purpose The Adjuvant chemoRadioTherapy In Stomach Tumors 2 (ARTIST 2) trial was conducted to compare the efficacy between adjuvant chemotherapy regimens and chemoradiotherapy in D2-resected, node-positive, stage 2 or 3 gastric cancer. Methods In this prospective, multicenter, phase IIItrial, we randomly assigned patients to three treatment arms: patients who receive adjuvant S-1 for 1 year, S-1 plus oxaliplatin (SOX) for 6 months, or SOX plus chemoradiotherapy (SOXRT). Herein, we report the safety outcomes of patients who received adjuvant chemotherapy or chemoradiotherapy. Results Among a total of 514 patients registered between February 2013 and December 2017, 499 patients who either completed or discontinued the assigned study treatments were included in the present analysis. Allthe three treatment arms were generally well-tolerated, with the overall treatment completion rate of 94% (96% in S-1, 93% in SOX, and 92% in SOXRT). The median delivered dose of radiotherapy in the SOXRT arm was 4,500 cGy (range, 0 to 4,500 cGy). The most frequently observed adverse events were fatigue (29%) in S-1 arm and peripheral neuropathy in the SOX and SOXRT arms (59% and 50%,respectively). Conclusion Our preliminary data confirm that there are no significant safety concerns in ARTIST 2 trial (ClinicalTrials.gov, NCT0176146). According to the Independent Data Monitoring Committee, patient accrual is underway.

The purpose of the present study was to investigate the clinical significance of preoperative hematological parameters in patients with advanced stomach cancer, and to explore who might benefit from adjuvant concurrent chemoradiotherapy (CCRT) compared to chemotherapy alone. Among 1032 patients with node-positive stomach cancer who had a confirmed diagnosis after complete D2 resection, and who received adjuvant chemotherapy alone or CCRT, a total of 692 patients was selected using propensity score matching. Among absolute neutrophil count, absolute lymphocyte count (ALC), absolute monocyte count (AMC), platelet count, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio, AMC was the most relevant prognostic factor for overall survival and recurrence-free survival (hazard ratio (HR) 1.674, 95% confidence interval (CI) 1.180–2.376; HR 1.908, 95% CI 1.650–2.695, respectively). In a subgroup with a high ALC, patients treated with adjuvant CCRT had a favorable recurrence-free survival (HR 0.620, 95% CI 0.393–0.980) compared to those treated with chemotherapy alone. Further study is needed to confirm our findings and to develop tailored adjuvant treatment.

Dietary education is regarded as an important and useful tool for influencing nutritional status. Since long, dietary education has been performed to improve the nutritional status of patients after a gastrectomy. This study aimed to investigate the effect of simplified dietary education on the nutritional status of patients after a gastrectomy. A total of 1,150 patients with gastric cancer underwent surgery between March 2014 and October 2015 at the Samsung Medical Center (SMC). Of these, we used the case-control matching method (1:1 match) by stratifying the factors of age and sex and included 100 patients in each group. The clinicopathologic data of the patients for two years after the gastrectomy were prospectively collected and retrospectively analyzed. The educated group (ED, N = 100) was provided with a simplified, ordinary dietary education at regular outpatient clinic visits that occurred at 1, 3, 6, and 12 months after gastrectomy and at 1-year intervals thereafter. The clinicopathologic characteristics and nutritional parameters of the educated group (ED) (N = 100) and the non-educated group (NED) (n = 100) were compared. There were no significant differences between the two groups in terms of clinical characteristics and serological parameters. Nutritional parameters, which included body weight loss, body mass index (BMI) change, and prognostic nutritional index (PNI), were also not significantly different between the two groups. Simplified dietary education at regular outpatient clinic visits was ineffective in reducing weight loss after a subtotal gastrectomy. Further research or other methods may be needed to reduce weight loss after a gastrectomy.

Abstract Background Due to a lack of consensus on adjuvant treatments for pT1N1 gastric cancer, surgeons face a dilemma when deciding treatments for patients with pT1N1 gastric cancer after gastrectomy. The objective of this study was to determine survival benefits of adjuvant chemotherapy and risk factors for tumor recurrence in gastric cancer patients with pT1N1. Methods Between 1996 and 2010, 510 patients who underwent curative resection for pT1N1 gastric cancer at three institutes were divided into two groups: adjuvant chemotherapy group (N = 150) and surgery-only group (N = 360). Disease-free survival rates and risk factors for tumor recurrence were analyzed. Results During the median follow-up of 78 months, 7.5% of patients experienced tumor recurrence (7.3% in adjuvant chemotherapy group and 7.5% in surgery-only group). The 5-year disease-free survival rate was 91.8% in the adjuvant chemotherapy group and 94.6% in the surgery-only group without significant difference between the two. In univariate analysis, older age (>65 years), male gender, body mass index

Tumor infiltrating lymphocytes (TIL) in Epstein-Barr virus (EBV)-associated/microsatellite-unstable (MSI) gastric carcinomas (GC) constitute immune-active principal cellular components of tumor microenvironment and contribute to better prognosis. With the remarkable success of cancer immunotherapies, there is an urgent need for a comprehensive understanding of tumor-immune interactions in patients with GC in the context of host immune response. To identify GC subtype-specific immune response gene set, we tested differentially expressed genes for MSI and EBV+ GC subtypes in randomly selected test set (n = 278) in merged ACRG-SMC microarray and TCGA RNA sequencing data set. We identified Host ImmunE Response index (HIERÏ) consisting of 29 immune genes classifying GC patients into robust 3 groups with prognostic significance. Immune-high cluster 1 was enriched with PD-L1High/EBV+/MSI/TILHigh with the best clinical outcome while immune-low cluster 3 displayed worst outcome and exemplified with PD-L1Low/EBV-/MSS. The results were validated in the same cohort (n = 279) and independent cohort (n = 181) with RNA from formalin-fixed paraffin-embedded (FFPE) tissue. Unexpectedly, nearly half of GC in cluster 1 were EBV-/MSS and 10% of cluster 3 GC were EBV+/MSI GC patients, suggesting that in addition to EBV+/MSI GC subtypes, EBV-/MSS subtype also constitutes almost half of high immune cluster and would be a good candidate for immune checkpoint inhibitor therapy. In contrary, almost 10% of EBV+/MSI GC patients may not respond to immune checkpoint inhibitor therapy. Thus, our HIERÏ gene signature demonstrates the potential to subclassify tumor immunity levels, predict prognosis and help immunotherapeutic decisions.

There is a consensus that cancer care should go beyond physical care as cancer patients and their family caregivers experience psychological burden, financial difficulty, as well as social relation issues. The current study aimed to investigate the moderating impact of social support on depression and anxiety of cancer patients and their family caregivers.Gastric cancer patients and their family caregivers who visited a university medical center in Seoul were approached for participation in the study. Fifty-two pairs of adult patients and caregivers participated in the study. Along with demographic information and the physical condition of the patients, such as pre-operation cancer stage and the type of gastrectomy, social support, depression, and anxiety were measured for patients and caregivers, respectively.In the first round of analysis, patients' depression was associated with age, while patients' anxiety was related to income. On the other hand, caregivers' depression was not associated with patients' health and living arrangement. In the second round of analysis to examine the moderating effect of social support, patients' income and social support were related to depression and anxiety, but the interaction of income and social support was only observed for anxiety. For caregivers, no interaction effects were found. Social support decreased the negative effects of low income status on the patients.While the income of the families with cancer cannot be adjusted in the short-term, their experience of social support can be managed by a proper support system. Diverse implications in medical settings are discussed.

The purpose of this study is to compare the effect of diabetes control induced by Roux-en-Y gastrojejunostomy(RY) vs Billroth-I reconstruction(BI) after distal gastrectomy in patients with early gastric cancer(EGC) and type 2 diabetes(T2DM). Forty EGC patients with T2DM, aged 20-80 years, who were expected to undergo curative distal gastrectomy were randomized 1:1 to RY(n = 20) or BI(n = 20). Diabetes medication status, biochemical and hormonal data including blood glucose, HbA1c, insulin, C-peptide, HOMA-IR, ghrelin, leptin, GLP-1, PYY, and GIP were evaluated for 12 months after surgery. Although pre- and postoperative 12-month fasting and postprandial glucose levels did not show a significant difference, HbA1c, C-peptide, and HOMA-IR levels were significantly improved at 12 months after surgery in both BI and RY groups. Sixty percent of RY patients and 20% of BI patients decreased their medication satisfying FBS

Background. We investigated the results of quality control study prior to phase III trial of sentinel lymph node navigation surgery (SNNS). Methods. Data were reviewed from 108 patients enrolled in the feasibility study of laparoscopic sentinel basin dissection (SBD) in gastric cancer. Seven steps contain tracer injection at submucosa (step 1) and at four sites (step 2) by intraoperative esophagogastroduodenoscopy (EGD), leakage of tracer (step 3), injection within 3 minutes (step 4), identification of at least one sentinel basin (SB) (step 5), evaluation of sentinel basin nodes (SBNs) by frozen biopsy (step 6), and identification of at least five SBNs at back table and frozen sections (step 7). Results. Failure in step 7 (n=23) was the most common followed by step 3 (n=15) and step 6 (n=13). We did not find any differences of clinicopathological factors between success and failure group in steps 1~6. In step 7, body mass index (BMI) was only the significant factor. The success rate was 97.1% in patients with BMI

Screening endoscopies in individuals 40 years or older in regions where gastric cancer is prevalent increase the diagnosis of gastric cancer at an early stage. However, the benefits of screening endoscopies in a young population (24 month group (23.8 mm [standard deviation, 22.2 mm] vs. 30.5 mm [standard deviation, 23.1 mm], P = 0.008). However, the proportion of patients with early gastric cancer did not differ between the two groups (≤24 months vs. >24 months group; 67.6% vs. 65.7%, P = 0.712). On multivariable analysis, periodic endoscopies did not influence the early diagnosis of gastric cancer (with >24 months as the reference group: ≤24 months, odds ratio = 0.939, 95% confidence interval = 0.583-1.513).Although periodic endoscopies aided in the detection of gastric cancer when lesions were smaller in size, they seemed not to increase the proportion of patients with early gastric cancer in young patients diagnosed with resectable gastric cancer.

Although changing a lymph node staging system from an anatomically based system to a numerically based system in gastric cancer offers better prognostic performance, several problems can arise: it does not offer information on the anatomical extent of disease and cannot represent the extent of lymph node dissection. The purpose of this study was to discover an alternative lymph node staging system for gastric cancer. Data from 6025 patients who underwent gastrectomy for primary gastric cancer between January 2000 and December 2010 were reviewed. The lymph node groups were reclassified into lesser-curvature, greater-curvature, and extra-perigastric groups. Presence of any metastatic lymph node in one group was considered positive. Lymph node groups were further stratified into four (new N0-new N3) according to the number of positive lymph node groups. Survival outcomes with this new N staging were compared with those of the current TNM system. For validation, two centers in Japan (large center, n = 3443; medium center, n = 560) were invited. Even among the same pN stages, the more advanced new N stage showed worse prognosis, indicating that the anatomical extent of metastatic lymph nodes is important. The prognostic performance of the new staging system was as good as that of the current TNM system for overall advanced gastric cancer as well as lymph node-positive gastric cancer (Harrell C-index was 0.799, 0.726, and 0.703 in current TNM and 0.799, 0.727, and 0.703 in new TNM stage). Validation sets supported these outcomes. The new N staging system demonstrated prognostic performance equal to that of the current TNM system and could thus be used as an alternative.

Objective The improvement of carcass traits is essential for the Hanwoo industry because of the Hanwoo grade determination system, and genome-wide association study (GWAS) analysis is an instrumental tool for identifying the genetic factors that impact these traits. While GWAS analysis utilizing family data offers advantages in minimizing genetic bias, research on family-based GWAS in Hanwoo is currently lacking. Methods This study classified Group A using both parental and offspring genetic information, and Group B based solely on offspring genetic information, to compare GWAS analysis results of Hanwoo carcass traits. Results A total of 16 significant single nucleotide polymorphism (SNP) markers were identified in Group A, comprising 7 for carcass weight (CWT), 3 for back fat thickness (BFT), and 6 for marbling score (MS). In Group B, 7 significant SNP markers were identified, including 3 for CWT, 1 for eye muscle area, 1 for BFT, and 2 for MS. Functional annotation analysis revealed only one common function related to carcass traits between the groups, while protein-protein interaction analysis indicated more gene interactions in Group A. The reliability of estimated values for common SNP markers identified between the groups was higher in Group A. Conclusion GWAS analysis utilizing parental genetic information holds greater potential for application, owing to its higher reliability of estimated values and the ability to explore numerous candidate genes.

Abstract Medical plastic-appliance-based healthcare services, especially in dentistry, generate tremendous amounts of plastic waste. Given the physiological features of our mouth, it is desirable to substitute dental care plastics with viscoelastic and antimicrobial bioplastics. Herein, we develop a medical-grade and sustainable bioplastic that is viscoelastic enough to align the tooth positions, resists microbial contamination, and exhibits recyclable life cycles. In particular, we devise a molecular template involving entanglement-inducing and antimicrobial groups and prepare a silk fibroin-based dental care bioplastic. The generated compactly entangled structure endows great flexibility, toughness, and viscoelasticity. Therefore, a satisfactory orthodontic outcome is accomplished, as demonstrated by the progressive alignment of male rabbit incisors within the 2.5 mm range. Moreover, the prepared bioplastic exhibits resistance to pathogenic colonization of intraoral microbes such as Streptococcaceae and Veillonellaceae. Because the disentanglement of entangled domains enables selective separation and extraction of the components, the bioplastic can be recycled into a mechanically identical one. The proposed medical-grade and sustainable bioplastic could potentially contribute to a green healthcare future.

Abstract We previously demonstrated that felodipine, an L-type calcium channel blocker, inhibits LPS-mediated neuroinflammatory responses in BV2 microglial cells and wild-type mice. However, the effects of felodipine on tau pathology, a hallmark of Alzheimer's disease (AD), have not been explored yet. Therefore, in the present study, we determined whether felodipine affects neuroinflammation and tau hyperphosphorylation in 3-month-old P301S transgenic mice (PS19), an early phase AD mice model for tauopathy. Felodipine administration decreased tauopathy-mediated microglial activation and NLRP3 expression in PS19 mice but had no effect on tauopathy-associated astrogliosis. In addition, felodipine treatment significantly reduced tau hyperphosphorylation at S202/Thr205 and Thr212/Ser214 residues via inhibiting JNK/P38 signaling in PS19 mice. Collectively, our results suggest that felodipine significantly ameliorates tau hyper-phosphorylation and tauopathy-associated neuroinflammatory responses in AD mice model for tauopathy and could be a novel therapeutic agent for AD.

Abstract Background Calf diarrhea leads to high mortality rates and decreases in growth and productivity, causing negative effects on the livestock industry. Lactate is closely associated with metabolic acidosis in diarrheic calves. However, there have been no reports on lactate concentrations in Korean indigenous (Hanwoo) calves, especially those with diarrhea. This study aimed to determine the reference range of L-lactate and D-lactate concentrations in Hanwoo calves and to better understand the utility of lactate as predictive factors for acidemia in diarrheic calves. Results L-lactate and D-lactate concentrations were measured in healthy (n = 44) and diarrheic (n = 93) calves, and blood gas analysis was performed on diarrheic calves. The reference range in healthy calves was 0.2–2.25 mmol/L for L-lactate and 0.42–1.38 mmol/L for D-lactate. Diarrheic calves had higher concentrations of L-lactate and D-lactate than healthy calves. In diarrheic calves, L-lactate and D-lactate each had weak negative correlation with pH (r = − 0.31 and r = − 0.35). In diarrheic calves with hyper-L-lactatemia, the combined concentrations of L-lactate and D-lactate had moderate correlation with pH (r = − 0.51) and anion gap (r = 0.55). Receiver operating characteristic analysis showed D-lactate had fair predictive performance (AUC = 0.74) for severe acidemia, with an optimal cut-off value of > 1.43 mmol/L. The combined concentrations of L-lactate and D-lactate showed fair predictive performance for predicting acidemia (AUC = 0.74) and severe acidemia (AUC = 0.72), with cut-off values of > 6.05 mmol/L and > 5.95 mmol/L. Conclusions The determined reference ranges for L-lactate and D-lactate in Hanwoo calves enable the identification of hyper-L-lactatemia and hyper-D-lactatemia. Diarrheic calves exhibited increased lactate concentrations correlated with acid-base parameters. While the concentrations of L-lactate and D-lactate have limitations as single diagnostic biomarkers for predicting acidemia or severe acidemia, their measurement remains important, and L-lactate has the advantage of being measurable at the point-of-care. Assessing lactate concentrations should be considered by clinicians, especially when used alongside other clinical indicators and diagnostic tests. This approach can improve calf diarrhea management, contributing positively to animal welfare and providing economic benefits to farms.

As COVID-19 has become endemic, SARS-CoV-2 variants are becoming increasingly diverse, underscoring the escalating importance of global genomic surveillance. This study analyzed 86,762 COVID-19 samples identified in the Republic of Korea from September 2022 to November 2023. The results revealed a consistent increase in the prevalence of the XBB variants following the dominance of BN.1, with various XBB sub-lineages co-circulating in the Republic of Korea. The overall nucleotide diversity (π) among the SARS-CoV-2 genomes was 0.00155. Evolutionary analysis revealed that the average time interval between the first detection and estimated date of the most recent common ancestor of Korean XBB sub-lineages was 47 d, suggesting that the novel variants were efficiently identified in the Korean surveillance system. The mutation rate was determined to be in the range of 5.6 × 10–4 to 9.1 × 10–4 substitutions/site/year. In conclusion, this study provides insights into the genetic diversity and evolutionary interpretation of the XBB sub-lineages during the XBB wave in the Republic of Korea, highlighting the importance of continued genomic surveillance for emerging variants.

Abstract Maintaining epidermal homeostasis relies on a tightly organized process of proliferation and differentiation of keratinocytes. While past studies have primarily focused on calcium regulation in keratinocyte differentiation, recent research has shed light on the crucial role of lysosome dysfunction in this process. TLR adaptor interacting with SLC15A4 on the lysosome (TASL) plays a role in regulating pH within the endo-lysosome. However, the specific role of TASL in keratinocyte differentiation and its potential impact on proliferation remains elusive. In our study, we discovered that TASL deficiency hinders the proliferation and migration of keratinocytes by inducing G1/S cell cycle arrest. Also, TASL deficiency disrupts proper differentiation process in TASL knockout human keratinocyte cell line (HaCaT) by affecting lysosomal function. Additionally, our research into calcium-induced differentiation showed that TASL deficiency affects calcium modulation, which is essential for keratinocyte regulation. These findings unveil a novel role of TASL in the proliferation and differentiation of keratinocytes, providing new insights into the intricate regulatory mechanisms of keratinocyte biology.

IntroductionErlotinib is an epidermal growth factor receptor (EGFR) inhibitor that is approved by the FDA to treat non-small cell lung cancer (NSCLC). Several membrane receptors, including EGFR, interact with amyloid β (Aβ), raising the possibility that erlotinib could have therapeutic effects on Alzheimer's disease (AD). However, the effects of erlotinib on Aβ/tau-related pathology and cognitive function in mouse models of AD and its mechanisms of action have not been examined in detail.MethodsTo investigate the effects of erlotinib on cognitive function and AD pathology, 3 to 6-month-old PS19 mice and 3 to 3.5-month-old 5xFAD mice and WT mice were injected with vehicle (5% DMSO + 10% PEG + 20% Tween80 + 65% D.W.) or erlotinib (20 mg/kg, i.p.) daily for 14 or 21 days. Then, behavioral tests, Golgi staining, immunofluorescence staining, western blotting ELISA, and real-time PCR were conducted.Results and discussionWe found that erlotinib significantly enhanced short-term spatial memory and dendritic spine formation in 6-month-old P301S tau transgenic (PS19) mice. Importantly, erlotinib administration reduced tau phosphorylation at Ser202/Thr205 (AT8) and Thr231 (AT180) and further aggregation of tau into paired helical fragments (PHFs) and neurofibrillary tangles (NFTs) in 3-month-old and/or 6-month-old PS19 mice by suppressing the expression of the tau kinase DYRK1A. Moreover, erlotinib treatment decreased astrogliosis in 6-month-old PS19 mice and reduced proinflammatory responses in primary astrocytes (PACs) from PS19 mice. In 3- to 3.5-month-old 5xFAD mice, erlotinib treatment improved short-term spatial memory and hippocampal dendritic spine number and diminished Aβ plaque deposition and tau hyperphosphorylation. Furthermore, erlotinib-treated 5xFAD mice exhibited significant downregulation of astrocyte activation, and treating PACs from 5xFAD mice with erlotinib markedly reduced cxcl10 (reactive astrocyte marker) and gbp2 (A1 astrocyte marker) mRNA levels and proinflammatory cytokine mRNA and protein levels. Taken together, our results suggest that erlotinib regulates tau/Aβ-induced AD pathology, cognitive function, and Aβ/tau-evoked astrogliosis and therefore could be a potent therapeutic drug for ameliorating AD symptoms.

With outstanding therapeutic potential in the tissue regeneration and anti-inflammation, mesenchymal stem cell-derived exosomes (MSC-EXOs) have emerged as a prominent therapeutic in recent. However, poor production yield and reproducibility have remained as significant challenges of their practical applications. To surmount these challenges, various alternative materials with stem cell-like functions, have been recently investigated, however, there has been no comprehensive analysis in these alternatives so far. Here, we discuss the recent progress of alternatives of MSC-EXOs, including exosomes and exosome-like nanovesicles from various biological sources such as plants, milk, microbes, and body fluids. Moreover, we extensively compare each alternative by summarizing their unique functions and mode of actions to suggest the expected therapeutic target and future directions for developing alternatives for MSC-EXOs.

Bovine hemolytic anemia has a negative impact on animal welfare and productivity due to its associated clinical symptoms. Hemolysis is generally known to cause reticulocytosis, increased indirect bilirubin, decreased concentration of haptoglobin, and increased lactate dehydrogenase. Additionally, tissue hypoperfusion due to concomitant anemia increases blood lactate concentration. However, few studies have reported the correlation between these indicators and hemolytic anemia in cattle. We expected that alterations in hematological and biochemical parameters could identify cattle with hemolytic anemia. Therefore, in addition to reporting differences in indicators according to hemolytic anemia, this study aimed to derive indicators and set criteria for identification of bovine hemolytic anemia. In cattle with hemolytic anemia, reticulocytosis, increased indirect bilirubin, and increased L-lactate were observed, and the correlation of these indicators with hematocrit (HCT) was confirmed. And since HCT alone has limitations in identifying hemolytic anemia, we suggest additional criteria to identify hemolytic anemia in cattle.

Abstract Aim To analyse and describe the trends concerning nurse–parent partnerships in South Korean research, presenting their implications in paediatric care and guiding future directions for partnership research. Design A scoping review. Methods The scoping review was conducted according to the framework outlined by Arksey and O'Malley. This review method consists of five stages: (1) identifying a research question, (2) identifying relevant studies, (3) selecting relevant studies, (4) charting the data extraction and (5) collating, summarizing and reporting the results. The studies reviewed were searched from electronic databases. Results Thirty studies were analysed for general characteristics, type of research method and findings from quantitative and qualitative research. Among the quantitative research, factors associated with partnerships, such as self‐efficacy, quality of care and coping, were commonly associated with nurse–parent partnerships regardless of parent‐, child‐ and nurse‐related factors. The intervention methods included active parental participation and the development of educational materials. In the review of qualitative research, parents and paediatric nurses experienced that even when both groups occupied the same environment simultaneously, a disparity existed between the paediatric nurses' and parents' perceptions of their partnership experiences. Implications for the Profession Strengthening nurse‐parent partnerships is crucial in improving health outcomes and quality of life for paediatric patients in South Korea. Effective collaboration, emphasizing mutual respect, effective communication, and shared decision‐making, is essential in paediatric nursing care. This requires ongoing research, including both parents and a multidisciplinary approach to build supportive relationships across various age groups. Recognizing parents as key members of the care team, with valuable insights and contributions, enhances care quality. Additionally, enhancing paediatric nurses' self‐efficacy, empowerment, and communication skills through continuous education is vital to improving parents' perceived quality of nursing. Partnership‐centred practices not only boost care quality but also fortify the bond between healthcare providers and families, promoting better health outcomes. No Patient or Public Contribution This work did not incorporate patient or public contributions, as its methodology was centred on a scoping review approach.

Abstract To realize economically feasible electrochemical CO2 conversion, achieving a high partial current density for value-added products is particularly vital. However, acceleration of the hydrogen evolution reaction due to cathode flooding in a high-current-density region makes this challenging. Herein, we find that partially ligand-derived Ag nanoparticles (Ag-NPs) could prevent electrolyte flooding while maintaining catalytic activity for CO2 electroreduction. This results in a high Faradaic efficiency for CO (>90%) and high partial current density (298.39 mA cm‒2), even under harsh stability test conditions (3.4 V). The suppressed splitting/detachment of Ag particles, due to the lipid ligand, enhance the uniform hydrophobicity retention of the Ag-NP electrode at high cathodic overpotentials and prevent flooding and current fluctuations. The mass transfer of gaseous CO2 is maintained in the catalytic region of several hundred nanometers, with the smooth formation of a triple phase boundary, which facilitate the occurrence of CO2RR instead of HER. We analyze catalyst degradation and cathode flooding during CO2 electrolysis through identical-location transmission electron microscopy and operando synchrotron-based X-ray computed tomography. This study develops an efficient strategy for designing active and durable electrocatalysts for CO2 electrolysis.

Abstract Dopamine plays important roles in cognitive function and inflammation and therefore is involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Drugs that increase or maintain dopamine levels in the brain could be a therapeutic strategy for AD. However, the effects of dopamine and its precursor levodopa (L-DOPA) on Aβ/tau pathology in vivo and the underlying molecular mechanisms have not been studied in detail. Here, we investigated whether L-DOPA treatment alters neuroinflammation, Aβ pathology, and tau phosphorylation in 5xFAD mice, a model of AD. We found that L-DOPA administration significantly reduced microgliosis and astrogliosis in 5xFAD mice. In addition, L-DOPA treatment significantly decreased Aβ plaque number by upregulating NEP and ADAM17 levels in 5xFAD mice. However, L-DOPA-treated 5xFAD mice did not exhibit changes in tau hyperphosphorylation or tau kinase levels. These data suggest that L-DOPA alleviates neuroinflammatory responses and Aβ pathology but not tau pathology in this mouse model of AD.

Abstract Inflammatory bowel disease (IBD) is a chronic inflammatory condition that is influenced by various factors, including environmental factors, immune responses, and genetic elements. Among the factors that influence IBD progression, macrophages play a significant role in generating inflammatory mediators, and an increase in the number of activated macrophages contributes to cellular damage, thereby exacerbating the overall inflammatory conditions. HSPA9, a member of the heat shock protein 70 family, plays a crucial role in regulating mitochondrial processes and responding to oxidative stress. HSPA9 deficiency disrupts mitochondrial dynamics, increasing mitochondrial fission and the production of reactive oxygen species. Based on the known functions of HSPA9, we considered the possibility that HSPA9 reduction may contribute to the exacerbation of colitis and investigated its relevance. In a dextran sodium sulfate-induced colitis mouse model, the downregulated HSPA9 exacerbates colitis symptoms, including increased immune cell infiltration, elevated proinflammatory cytokines, decreased tight junctions, and altered macrophage polarization. Moreover, along with the increased mitochondrial fission, we found that the reduction in HSPA9 significantly affected the superoxide dismutase 1 levels and contributed to cellular death. These findings enhance our understanding of the intricate mechanisms underlying colitis and contribute to the development of novel therapeutic approaches for this challenging condition.

Abstract Background Ulinastatin, an anti-inflammatory and antioxidant trypsin inhibitor, has shown potential in mitigating acute kidney injury (AKI) and reducing serum creatinine levels after various surgeries. This retrospective study aimed to evaluate the effects of ulinastatin on AKI in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. Methods We hypothesized that the administration of ulinastatin could prevent AKI in OPCAB. Electrical medical records were reviewed to identify OPCAB patients between January 2015 and June 2020. The utilization of ulinastatin was randomly determined and applied during this period. Acute kidney injury was defined according to the KDIGO guideline, and its incidence was compared between the ulinastatin administration group and the control group. To investigate the effect of ulinastatin on renal function, multivariate logistic regression analysis was used to calculate propensity scores for each group. Results A total 454 OPCAB were performed, and after following inclusion and exclusion process, 100 patients were identified in the ulinastatin group and 303 patients in the control group. Using 1:2 propensity score matching, we analyzed 100 and 200 patients in the ulinastatin and control groups. The incidence of AKI was similar between the groups (2.5% for the control group, 2.0% for the ulinastatin group, p > 0.999). However, the serum creatinine value on the first post-operative day were significantly lower in the ulinastatin group compared to the control group (0.774 ± 0.179 mg/dL vs 0.823 ± 0.216 mg/dL, P = 0.040), while no significant differences were observed for the other time points (P > 0.05). The length of ICU stay day was significantly shorter in the ulinastatin group (2.91 ± 2.81 day vs 5.22 ± 7.45 day, respectively, P

Abstract Guided bone regeneration aided by the application of occlusive membranes is a promising therapy for diverse inflammatory periodontal diseases. Symbiosis, homeostasis between the host microbiome and cells, occurs in the oral environment under normal, but not pathologic, conditions. Here, we develop a symbiotically integrating occlusive membrane by mimicking the tooth enamel growth or multiple nucleation biomineralization processes. We perform human saliva and in vivo canine experiments to confirm that the symbiotically integrating occlusive membrane induces a symbiotic healing environment. Moreover, we show that the membrane exhibits tractability and enzymatic stability, maintaining the healing space during the entire guided bone regeneration therapy period. We apply the symbiotically integrating occlusive membrane to treat inflammatory-challenged cases in vivo, namely, the open and closed healing of canine premolars with severe periodontitis. We find that the membrane promotes symbiosis, prevents negative inflammatory responses, and improves cellular integration. Finally, we show that guided bone regeneration therapy with the symbiotically integrating occlusive membrane achieves fast healing of gingival soft tissue and alveolar bone.

Abstract Background Despite the diverse genetic mutations in head and neck cancer, the chemotherapy outcome for this cancer has not improved for decades. It is urgent to select prognostic factors and therapeutic targets for oropharyngeal cancer to establish precision medicine. Recent studies have identified PSMD1 as a potential prognostic marker in several cancers. We aimed to assess the prognostic significance of PSMD1 expression in oropharyngeal squamous cell carcinoma (OPSCC) patients using immunohistochemistry. Methods We studied 64 individuals with OPSCC tissue from surgery at Seoul National University Bundang Hospital between April 2008 and August 2017. Immunostaining analysis was conducted on the tissue microarray (TMA) sections (4 μm) for p16 and PSMD1. H-score, which scale from 0 to 300, was calculated from each nucleus, cytoplasm, and cellular expression. Clinicopathological data were compared with Chi-squared test, Fisher’s exact test, t-test, and logistic regression. Survival data until 2021 were achieved from national statistical office of Korea. Kaplan–Meier method and cox-regression model were used for disease-specific survival (DSS) analysis. Results H-score of 90 in nucleus was appropriate cutoff value for ‘High PSMD1 expression’ in OPSCC. Tonsil was more frequent location in low PSMD1 group (42/52, 80.8%) than in high PSMD1 group (4/12, 33.3%; P = .002). Early-stage tumor was more frequent in in low PSMD1 group (45/52, 86.5%) than in high PSMD1 group (6/12, 50%; P = .005). HPV was more positive in low PSMD1 group (43/52, 82.7%) than in high PSMD1 group (5/12, 41.7%; P = .016). Patients with PSMD1 high expression showed poorer DSS than in patients with PSMD1 low expression (P = .006 in log rank test). In multivariate analysis, PSMD1 expression, pathologic T staging, and specimen age were found to be associated with DSS (P = .011, P = .025, P = .029, respectively). Conclusions In our study, we established PSMD1 as a negative prognostic factor in oropharyngeal squamous cell carcinoma, indicating its potential as a target for targeted therapy and paving the way for future in vitro studies on drug repositioning.

Honeybees play a crucial role as agricultural pollinators and are frequently exposed to various pollutants, including pesticides. In this study, we aimed to evaluate the toxicity of lambda-cyhalothrin (LCY) and spinetoram (SPI) in honey bee larvae reared in vitro through single (acute) and repeated (chronic) exposure. The acute LD50 values for LCY and SPI were 0.058 (0.051–0.066) and 0.026 (0.01–0.045) μg a.i./larva, respectively. In chronic exposure, the LD50 values of LCY and SPI were 0.040 (0.033–0.046) and 0.017 (0.014–0.019) μg a.i./larva, respectively. The chronic no-observed-effect dose of LCY and SPI was 0.0125 μg a.i./larva. Adult deformation rates exceeded 30% in all LCY treatment groups, showing statistically significant differences compared to the solvent control group (SCG). Similarly, SPI-treated bees exhibited significantly more deformities than SCG. Furthermore, we examined the activities of several enzymes, namely, acetylcholinesterase (AChE), glutathione-S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD), in larvae, pupae, and newly emerged bees after chronic exposure at the larval stage (honey bee larval chronic LD50, LD50/10 (1/10th of LD50), and LD50/20 (1/20th of LD50)). LCY and SPI induced significant changes in detoxification (GST), antioxidative (SOD and CAT), and signaling enzymes (AChE) during the developmental stages (larvae, pupae, and adults) of honey bees at sublethal and residue levels. Our results indicate that LCY and SPI may affect the development of honey bees and alter the activity of enzymes associated with oxidative stress, detoxification, and neurotransmission. These results highlight the potential risks that LCY and SPI may pose to the health and normal development of honey bees.

Objective When evaluating individuals with the same parent and no phenotype by pedigree best linear unbiased prediction (BLUP), it is difficult to explain carcass grade difference and select individuals because they have the same value in pedigree BLUP (PBLUP). However, single step GBLUP (ssGBLUP), which can estimate the breeding value suitable for the individual by adding genotype, is more accurate than the existing method. Methods The breeding value and accuracy were estimated with pedigree BLUP and ssGBLUP using pedigree and genotype of 408 Hanwoo cattle from 16 families with the same parent among siblings produced by fertilized egg transplantation. A total of 14,225 Hanwoo cattle with pedigree, genotype and phenotype were used as the reference population. PBLUP obtained estimated breeding value (EBV) using the pedigree of the test and reference populations, and ssGBLUP obtained genomic EBV (GEBV) after constructing and H-matrix by integrating the pedigree and genotype of the test and reference populations. Results For all traits, the accuracy of GEBV using ssGBLUP is 0.18 to 0.20 higher than the accuracy of EBV obtained with PBLUP. Comparison of EBV and GEBV of individuals without phenotype, since the value of EBV is estimated based on expected values of alleles passed down from common ancestors. It does not take Mendelian sampling into consideration, so the EBV of all individuals within the same family is estimated to be the same value. However, GEBV makes estimating true kinship coefficient based on different genotypes of individuals possible, so GEBV that corresponds to each individual is estimated rather than a uniform GEBV for each individual. Conclusion Since Hanwoo cows bred through embryo transfer have a high possibility of having the same parent, if ssGBLUP after adding genotype is used, estimating true kinship coefficient corresponding to each individual becomes possible, allowing for more accurate estimation of breeding value.

Abstract Background REGATTA trial failed to demonstrate the survival benefit of reduction gastrectomy in patients with advanced gastric cancer with a single non‐curable factor. However, a significant interaction was found between the treatment effect and tumor location in the subset analysis. Additionally, the treatment effect appeared to be different between Japan and Korea. This supplementary analysis aimed to elucidate the effect of reduction surgery based on tumor location and country. Methods Multivariable Cox regression analyses in each subgroup were performed to estimate the hazard ratio (HRadj), including the following variables as explanatory variables: country, age, sex, incurable factor, cT, cN, primary tumor, performance status, histological type, and macroscopic type. Results Patients (95 in Japan and 80 in Korea) were randomized to chemotherapy alone (86 patients) or gastrectomy plus chemotherapy (89 patients). The subgroup analysis according to the country revealed a worse overall survival in gastrectomy plus chemotherapy arm in Japan (hazard ratio: 1.32, 95% confidence interval: 0.85–2.05), but not in Korea (hazard ratio: 0.85.95% confidence interval: 0.52–1.40). Overall survival was better in distal gastrectomy plus chemotherapy compared with chemotherapy alone (hazard ratio = 0.69, 95% confidence interval: 0.42–1.13), and worse in total gastrectomy plus chemotherapy compared with chemotherapy alone (hazard ratio = 1.34, 95% CI: 0.93–1.94), which was more remarkable in Korea than in Japan. Conclusions Primary chemotherapy is a standard of care for advanced gastric cancer; however, the survival benefits from reduction by distal gastrectomy remained controversial.

Abstract The occurrence of osteoporosis gradually increases within the aging population. As the side effects of therapeutic agents currently used for osteoporosis are increasing, the development of preventive and therapeutic agents derived from natural products without any long-term side effects is important. Here, we investigated the effect of wheat seedling extract (WSE) on the RANKL-mediated differentiation, fusion, and function of osteoclasts. WSE inhibited the differentiation of RANKL-induced bone marrow macrophages and phosphorylation of AKT and ERK. Moreover, the protein and mRNA expression levels of c-Fos and NFATc1 as well as RANKL-induced transcription of TRAP and OSCAR were suppressed by WSE treatment. DC-STAMP and cathepsin K, which are essential for cell fusion and bone degradation, were also inhibited by WSE. Furthermore, eight components constituting WSE were confirmed to decrease the osteoclast TRAP activity. Taken together, WSE may have potential implications as a useful therapeutic or preventive agent for inhibition of bone loss.

Abstract Alzheimer’s disease (AD) is a neurodegenerative disease characterized by Aβ deposition, tauopathy, neuroinflammation, and impaired cognition. The recent identification of associations between protein kinases and AD pathology has spurred interest in tyrosine kinase inhibitors (TKIs) as potential strategic therapeutic agents for AD. In the present study, we investigated whether the TKIs ibrutinib, PD180970, and cabozantinib, which have different on-targets, selectively regulate AD pathology in 3.5- to 4-month-old 5xFAD mice (a model of the early phase of AD). Ibrutinib (10 mg/kg, i.p.) effectively reduced amyloid-β (Aβ) plaque number, tau hyperphosphorylation and neuroinflammation in 5xFAD mice. Surprisingly, PD180970 (10 mg/kg, i.p.) did not alter Aβ plaque number or neuroinflammatory responses and exacerbated tau hyperphosphorylation in 5xFAD mice. Cabozantinib (10 mg/kg, i.p.) had no effect on amyloidopathy but partially relieved tau hyperphosphorylation and astrogliosis. Taken together, our results suggest that not all TKIs have therapeutic effects on AD pathology in a mouse model of AD. Consequently, optimization of drug dosage, injection periods and administration routes should be considered when repurposing TKIs as novel AD therapeutics.

Background Since the onset of the coronavirus disease 2019 pandemic, virtual simulation has emerged as an alternative to traditional teaching methods as it can be employed within the recently established contact-minimizing guidelines. This prospective education study aimed to develop a virtual reality simulator for a lumbar transforaminal epidural block (LTFEB) and demonstrate its efficacy. Methods We developed a virtual reality simulator using patient image data processing, virtual X-ray generation, spatial registration, and virtual reality technology. For a realistic virtual environment, a procedure room, surgical table, C-arm, and monitor were created. Using the virtual C-arm, the X-ray images of the patient’s anatomy, the needle, and indicator were obtained in real-time. After the simulation, the trainees could receive feedback by adjusting the visibility of structures such as skin and bones. The training of LTFEB using the simulator was evaluated using 20 inexperienced trainees. The trainees’ procedural time, rating score, number of C-arm taken, and overall satisfaction were recorded as primary outcomes. Results The group using the simulator showed a higher global rating score (P = 0.014), reduced procedural time (P = 0.025), reduced number of C-arm uses (P = 0.001), and higher overall satisfaction score (P = 0.007). Conclusions We created an accessible and effective virtual reality simulator that can be used to teach inexperienced trainees LTFEB without radiation exposure. The results of this study indicate that the proposed simulator will prove to be a useful aid for teaching LTFEB.

Cervical cancer, which is mainly caused by oncogenic human papillomavirus subtypes, remains a significant global health challenge. Recent studies have indicated a connection between cervical cancer and the uterine microbiome, underscoring its importance. This study explored the potential of liquid-based cytology (LBC) samples, which are typically used for cytological analysis, in investigating the cervical microbiome. Thirty women participated in the study and provided clinical information. Three samples were obtained from each participant: one for clinical purposes using LBC, another for microbiome sampling using LBC, and a third using the SWAB Microbiome kit. The LBC and traditional swab (SWAB) samples were subjected to high-throughput 16S rRNA gene sequencing for microbiome analysis. The results revealed a consistent dominance of key taxa, particularly Lactobacillus spp. The analysis of differential abundance highlighted variations in microbial abundance among individuals, which were more prominent than those resulting from the sampling methods. Functional analysis identified arachidonic acid and alpha-linolenic acid metabolism, along with a cautionary note regarding the low mean proportion values. The network analysis revealed positive correlations between indicators of structure among the networks, highlighting the robustness of microbiome similarities despite the diversity of sampling methods. Supervised machine learning has revealed challenges in distinguishing LBC and SWAB samples based on their microbiome features. Weighted co-expression network analysis revealed that the correlation between microbial clusters and the sampling method with clinical data was not significant. This study emphasizes the similarity in microbial communities observed using the LBC and SWAB methods, highlighting the potential of using dual diagnostic approaches. Additionally, the use of residual LBC samples in large-scale microbiological studies can provide comprehensive insights into cervical health and disease.

More than 20% of the world’s population suffers from allergic diseases, including allergic asthma, rhinitis, and atopic dermatitis that severely reduce the patient’s quality of life. The treatment of allergy has been developed, but there are still unmet needs. Ampelopsis brevipedunculata (Maxim.) Trautv. is a traditional medicinal herb with beneficial bioactivities, such as antioxidant, anti-hypertension, anti-viral, anti-mutagenic, and skin and liver (anti-hepatotoxic) protective actions. However, its anti-allergic effect has not been addressed. This study designed to investigate the pharmacological effect of an ethanol extract of A. brevipedunculata rhizomes (ABE) on mast cell and anaphylaxis models. For in vivo studies, we used ovalbumin-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models. In ASA model, oral administration of ABE (1, 10, and 100 mg/kg) attenuated the anaphylactic responses, such as hypothermia, serum histamine, and IgE productions. In PCA model, ABE also suppressed the plasma extravasation and swelling. The underlying mechanisms of action were identified in various mast cell types. In vitro, ABE (10, 30, and 60 µg/mL) inhibited the release of essential allergic mediators, such as histamine and β-hexosaminidase, in a concentration-dependent manner. ABE prevented the rapid increase in intracellular calcium levels induced by the DNP-HSA challenge. In addition, ABE downregulated the tumor necrosis factor-α and interleukin-4 by suppressing the activation of nuclear factor-κB. Collectively, this study is the first to identify the anti-allergic effect of ABE, suggesting that ABE is a promising candidate for treating allergic diseases.

Background: The utilization of herbal medicine has been noteworthy for treating cancer; however, there is not enough information regarding the characteristics of clinical trials of herbal medicine interventions. This study aimed to evaluate the characteristic of registered trials using herbal medicine interventions for cancer. Methods: A cross-sectional study was performed via the website ClinicalTrials.gov, ISRCTN registry, Chinese clinical trial registry, and international clinical trials registry platform to gather associated registered clinical trials using an advanced search with the developed keyword strategy as of March 26, 2023. All obtainable information from the trials was collected without any restrictions to conduct a comprehensive review. Results: A total of 169 registered trials were included for evaluation. Of all trials, 102 trials were eligible for this study. Countries from Asia registered the most trials (62.75%), and hospitals sponsored most of the trials (42.16%). Randomized, Phase 2, interventional trials were dominant, and approximately 64.71% of the trials anticipated recruiting less than 100 participants. More than half of the trials were from 2016 to 2023 (53.92%). While 45 trials were completed, only 16 trials had results for further analysis. According to the completed results, the types of herbal medicines from the trials mainly focused on lung, breast, and colorectal cancer. Conclusion: This study is the first to explore the characteristics of clinical trials of herbal medicine for cancer registered in large clinical databases. The acquired trials had relatively informative data; however, better-designed trials may be needed for health professionals to consider herbal medicine as an option when treating cancer patients.

The Shaan virus is a new paramyxovirus species recently isolated from an insectivorous bat. Therefore, its replication characteristics remain unclear. We used transcriptome analysis and molecular experiments to examine host cell responses in human A549, HEK293, and monkey MARC-145 cell lines infected with the Shaan virus (ShaV/B16-40). Transcriptome data showed that Shaan virus infection induced innate immune responses associated with defense mechanisms against viral infection in all infected host cells. In real-time RT-PCR, IFN-α, -β and -λ1 were significantly upregulated in response to infection with Shaan virus in A549 and HEK-293 cells. However, the expression of IFN-α and -λ1 did not change in MARC-145 infected cells, while IFN-β significantly increased compared to the control in all the infected cell lines. In DEG analysis, the viperin expression pattern by Shaan virus infection varied depending on the host cell types or their origins. Viperin was highly induced at the RNA level by Shaan virus infection, and viperin protein expression was detected by western blotting. Although viperin, an ISG, has broad inhibitory effects on a range of viral pathogens, viperin knockdown or knock-in in the infected cells indicated that this protein did not markedly affect Shaan virus replication. Interestingly, these effects were independent of CMPK2 expression, which is beneficial for the antiviral effects of viperin. Therefore, the present results suggest that Shaan virus might have a strategy to evade the antiviral effect of viperin or not be significantly affected by viperin.

This perspective article discusses the relationship between religion, spirituality and health and emphasizes their continuing importance in today’s world. The article examines the portrayal of moderation in religious texts, such as the teachings of mindful eating, the mindfulness approach, and the concept of fasting in the context of current research on intermittent fasting. This article accentuates the connection between body and soul and attempts to offer a perspective that combines medicine and religious wisdom. It discusses the modern understanding of ancient wisdom to understand the complex relationship between religion, spirituality and health and its effect on human well-being. By linking ancient wisdom with relevant contemporary trends, we seek to illuminate new dimensions of holistic health care and underline the important role of interdisciplinary research. We also look at the general history of health, spirituality and urban landscapes and highlight their relevance today. Furthermore, we aim to contribute to critical theology by highlighting perspectives that link spiritual practices to measurable physiological outcomes. The study promotes a paradigm shift in healthcare in which spirituality is recognized as an important determinant of health. Future experiments are proposed to unravel the complex mechanisms by which spiritual practices influence well-being and pave the way for evidence-based interventions. In developing cities where intergenerational health is a priority, our findings argue for sustainable societies based on the enduring wisdom of spirituality. This study serves as a guidepost for future research aimed at a deeper understanding of the relationship between spirituality, health, and the urban environment.

Abstract Biofilms induce microbial-mediated surface roughening and deterioration of cement. In this study, zwitterionic derivatives (ZD) of sulfobetaine methacrylate (SBMA) and 2-methacryloyloxyethyl phosphorylcholine, were added in concentrations of 0, 1, and 3% to three different types of commercially available resin-modified glass ionomer cement (RMGIC) (RMC-I: RelyX Luting 2, RMC-II: Nexus RMGI, and RMC-III: GC FujiCEM 2). The unmodified RMGICs served as the control group for comparison. The resistance of Streptococcus mutans to ZD-modified RMGIC was evaluated with a monoculture biofilm assay. The following physical properties of the ZD-modified RMGIC were assessed: wettability, film thickness, flexural strength, elastic modulus, shear bond strength, and failure mode. The ZD-modified RMGIC significantly inhibited biofilm formation, with at least a 30% reduction compared to the control group. The addition of ZD improved the wettability of RMGIC; however, only 3% of the SBMA group was statistically different (P 0.05). The experimental groups' flexural strength, elastic modulus, and shear bond strength showed an insignificant decrease from the control group; there was no statistical difference within the RMC-I (P > 0.05). The mode of failure differed slightly in each group, but all groups showed dominance in the adhesive and mixed failure. Thus, the addition of 1 wt.% ZD in RMGIC favorably enhanced the resistance to Streptococcus mutans without any tangible loss in flexural and shear bond strength.

Conventional OPAs incorporating a diffraction grating were mainly developed to achieve a two-dimensional spot beam-based scan, which inevitably requires a wide range of wavelength tuning, leading to unaffordable complexity and limited scanning speed. In this study, we demonstrate a hybrid OPA that capitalizes on a silicon nitride line beam emitter based on tapered waveguides array, which facilitates efficient line beam scanning exhibiting flexible vertical field-of-views (FOVs) at a wavelength of 1550 nm. The line beam is horizontally scanned by driving an array of hybrid-integrated thermo-optic polymer phase modulators. The vertical FOV can be flexibly adjusted by varying the tip widths of the tapers and thus the angular divergence of emitted beams, leading to flexible FOVs ranging from 30° × 14° to 30° × 47°. A lens module is particularly devised and tethered to the OPA, thereby further tailoring and amplifying the FOVs along vertical and horizontal directions. The proposed hybrid OPA in conjunction with a lens module was practically manufactured to efficiently substantiate desired line beam scanning, achieving FOVs ranging from 51° × 0.6° to 51° × 10.3°. The developed line-beam-based OPA is anticipated to play an integral role in embodying an advanced LiDAR system featuring fast beam scanning.