An artificial intelligence system for comprehensive pathologic outcome prediction in early gastric cancer through endoscopic image analysis (with video).

BACKGROUND: Accurate prediction of pathologic results for early gastric cancer (EGC) based on endoscopic findings is essential in deciding between endoscopic and surgical resection. This study aimed to develop an artificial intelligence (AI) model to assess comprehensive pathologic characteristics of EGC using white-light endoscopic images and videos. METHODS: To train the model, we retrospectively collected 4,336 images and prospectively included 153 videos from patients with EGC who underwent endoscopic or surgical resection. The performance of the model was tested and compared to that of 16 endoscopists (nine experts and seven novices) using a mutually exclusive set of 260 images and 10 videos. Finally, we conducted external validation using 436 images and 89 videos from another institution. RESULTS: After training, the model achieved predictive accuracies of 89.7% for undifferentiated histology, 88.0% for submucosal invasion, 87.9% for lymphovascular invasion (LVI), and 92.7% for lymph node metastasis (LNM), using endoscopic videos. The area under the curve values of the model were 0.992 for undifferentiated histology, 0.902 for submucosal invasion, 0.706 for LVI, and 0.680 for LNM in the test. In addition, the model showed significantly higher accuracy than the experts in predicting undifferentiated histology (92.7% vs. 71.6%), submucosal invasion (87.3% vs. 72.6%), and LNM (87.7% vs. 72.3%). The external validation showed accuracies of 75.6% and 71.9% for undifferentiated histology and submucosal invasion, respectively. CONCLUSIONS: AI may assist endoscopists with high predictive performance for differentiation status and invasion depth of EGC. Further research is needed to improve the detection of LVI and LNM.

Impact of malnutrition and nutritional support after gastrectomy in patients with gastric cancer.

Malnutrition, characterized by altered body composition and impaired function, is particularly prevalent among gastric cancer patients, affecting up to 60% of them. Malnutrition in these patients can manifest both before and after surgery, due to factors such as gastric outlet obstruction, cancer cachexia, and anatomical changes. Notably, total gastrectomy (TG) presents the most significant nutritional challenges. However, function-preserving gastrectomy, such as pylorus-preserving gastrectomy (PPG) and proximal gastrectomy (PG), have shown promise in improving nutritional outcomes. Effective nutritional risk screening and assessment are vital for identifying patients at risk. Nutritional support not only improves nutritional parameters but also reduces complications, enhances quality of life (QoL) and survival rates. Those unable to maintain more than 50% of the recommended intake for over 7 days are recommended for nutritional support. Common methods of nutritional support include oral nutrition supplements (ONS), enteral nutrition (EN), or parenteral nutrition (PN) depending on the patient's status. Effect of perioperative nutritional support remains controversial. Preoperative interventions including ONS and PN have shown mixed results, with selective benefits in patients with sarcopenia or hypoalbuminaemia, while impact of EN in gastric outlet obstruction patients have been positive. In contrast postoperative support appears to be consistent. Tube feeding after TG has shown improvements, and ONS have been effective in reducing weight loss and improving nutritional biomarkers. PN was also associated with benefits such as weight maintenance and QoL. This review explores the mechanisms, assessment, and clinical impact of malnutrition, emphasizing the importance of nutritional support in gastric cancer patients undergoing gastrectomy.

Distinguishing Affective Temperament Profiles in Major Depressive Disorder and Bipolar Disorder Through the Short Version of TEMPS-A: Cross-Sectional Study Using Latent Profile Analysis.

OBJECTIVE: This study aimed to elucidate the distinct response patterns exhibited by patients diagnosed with bipolar disorder (BD) and those with major depressive disorder (MDD) through the application of the short version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A-SV). METHODS: A total of 2,458 participants consisting of patients with MDD (n=288), BD (BD I, n=111; BD II, n=427), and control group (n=1,632) completed the TEMPS-A-SV. The response patterns of the participants were classified into distinct profiles using latent profile analysis. The study further examined the impact of covariates such as age, sex, and diagnostic group on derived latent profile memberships. RESULTS: The following three latent profiles were identified: High Affective Temperament Group (17.86%), Low Affective Temperament Group (41.25%), and Middle Affective Temperament Group (40.89%). Compared with the patient group with MDD and BD, the control group was more likely to belong in the Low Affective Temperament Group, which showed a higher score on hyperthymic temperament than the Middle Affective Temperament Group. Furthermore, compared with the patients with BD, the MDD patients were more likely to be in the Low Affective Temperament Group rather than the Middle Affective Temperament Group. CONCLUSION: These results indicate that different affective temperaments exist between patients with MDD and BD. Attempting to classify response patterns using the TEMPS-A-SV can help diagnose MDD and BD correctly.

Culture-based susceptibility-guided tailored versus empirical concomitant therapy as first-line Helicobacter pylori treatment: A randomized clinical trial.

BACKGROUND: With the increasing resistance to antimicrobial agents, susceptibility-guided tailored therapy has been emerging as an ideal strategy for Helicobacter pylori treatment. However, susceptibility-guided tailored therapy requires additional cost, time consumption, and invasive procedure (endoscopy) and its superiority over empirical quadruple therapy as the first-line H. pylori treatment remains unclear. AIMS: To compare the efficacy of culture-based susceptibility-guided tailored versus empirical concomitant therapy as the first-line Helicobacter pylori treatment. METHODS: This open-label, randomized trial was performed in four Korean institutions. A total of 312 Patients with H. pylori-positive culture test and naïve to treatment were randomly assigned in a 3:1 ratio to either culture-based susceptibility-guided tailored therapy (clarithromycin-based or metronidazole-based triple therapy for susceptible strains or bismuth quadruple therapy for dual-resistant strains, n = 234) or empirical concomitant therapy (n = 78) for 10 days. Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment. RESULTS: Prevalence of dual resistance to both clarithromycin and metronidazole was 8%. H. pylori eradication rates for tailored and concomitant groups were 84.2% and 83.3% by intention-to-treat analysis (p = 0.859), respectively, and 92.9% and 91.5% by per-protocol analysis, respectively (p = 0.702), which were comparable between the two groups. However, eradication rates for dual-resistant strains were significantly higher in the tailored group than in the concomitant group. All adverse events were grade 1 or 2 based on the Common Terminology Criteria for Adverse Events and the incidence was significantly lower in the tailored group. The proportion of patients discontinuing treatment for adverse events was comparable between the two groups (2.1% vs. 2.6%). CONCLUSIONS: The culture-based susceptibility-guided tailored therapy failed to show superiority over the empirical concomitant therapy in terms of eradication rate. Based on these findings, the treatment choice in clinical practice would depend on the background rate of antimicrobial resistance, availability of resources and costs associated with culture and susceptibility testing.

The Effects of Microbial Additive Supplementation on Growth Performance, Blood Metabolites, Fecal Microflora, and Carcass Characteristics of Growing-Finishing Pigs.

This study aimed to assess the effects of microbial additives that produce antimicrobial and digestive enzymes on the growth performance, blood metabolites, fecal microflora, and carcass characteristics of growing-finishing pigs. A total of 180 growing-finishing pigs (Landrace × Yorkshire × Duroc; mixed sex; 14 weeks of age; 58.0 ± 1.00 kg) were then assigned to one of three groups with three repetitions (20 pigs) per treatment for 60 days of adaptation and 7 days of collection. Dietary treatments included 0, 0.5, and 1.0% microbial additives in the basal diet. For growth performance, no significant differences in the initial and final weights were observed among the dietary microbial additive treatments, except for the average daily feed intake, average daily gain, and feed efficiency. In terms of blood metabolites and fecal microflora, immunoglobulin G (IgG), blood urea nitrogen, blood glucose, and fecal lactic acid bacteria count increased linearly, and fecal E. coli counts decreased linearly with increasing levels of microbial additives but not growth hormones and Salmonella. Carcass quality grade was improved by the microbial additive. In addition, carcass characteristics were not influenced by dietary microbial additives. In conclusion, dietary supplementation with 1.0% microbial additive improved average daily gain, feed efficiency, IgG content, and fecal microflora in growing-finishing pigs.

The Association of Body Mass Index on Falls Risk and Mortality in Hospitalized Patients of Different Old-Age Categories Requiring Nutritional Support.

Malnutrition affect clinical outcomes in hospitalized old age patients, but the data on the related outcomes on the basis of different age categories are still limited. We aimed to investigate the interplay of associations among body mass index (BMI), falls risk, and mortality rate in different older adult patient age categories. This retrospective study included hospitalized patients aged ≥ 65 years who received artificial nutrition. Demographic, biochemical, and survival data were collected. BMI was evaluated using the World Health Organization BMI cutoffs for Asians, and patients were classified into high (≥ 23.0 kg/m2), normal (18.5-22.9 kg/m2), and low (< 18.5 kg/m2) BMI groups. The Morse Fall Scale was used to assess falls risk. By age categories, all patients (n = 4,642) were divided into the 65-74 (n = 2,649) and ≥ 75 (n = 1,993) years age groups. We found that the proportion of low-BMI and high risk of falls increased with age. Further, low-BMI was associated with increased falls risk in both age groups. Overall survival rate tended to be lower in the low-BMI and ≥ 75 years group than that in other patient groups, but did not differ significantly compared with the low-BMI and 65-74 years group. Low-BMI was associated with increased falls risk and mortality; however, the association depended on specific patient age groups.

The Impact of Morningness-Eveningness on Depression through a Serial Mediation Model of Resilience and Anxiety.

OBJECTIVE: Resilience has been recently considered one of the possible mechanisms for the association between morningness-eveningness and depression. Meanwhile, anxiety is closely associated with mood disorder, but its association with morningness-eveningness is unclear. Therefore, this study aimed to explore the mediating effects of resilience and anxiety on morningness-eveningness and depression as the possible mechanisms. METHODS: This study included patient group and nonpatient group. Patient group consists of 743 patients with mood disorders [Major Depressive Disorder (MDD), 233; Bipolar Disorder Ⅰ (BDⅠ), 113; Bipolar Disorder Ⅱ (BDⅡ), 397] whereas nonpatient group consists of 818 individuals without mood disorder. The Composite Scale of Morningness, Connor-Davidson Resilience Scale, Self-Rating Depression Scale, and Beck Anxiety Inventory were used to evaluate morningness-eveningness, resilience, anxiety, and depression, respectively. RESULTS: Our model provided a good fit for the data. The association between morningness-eveningness and depression symptoms was partially serially mediated by resilience and anxiety in both the patient and nonpatient groups. The patient group exhibited significantly stronger morningness-eveningness toward resilience and anxiety than the nonpatient group. In the indirect effect of morningness-eveningness on depression, group differences exist only through each mediation of resilience and anxiety, not through serial mediation. CONCLUSION: Our results expand on the mechanism underlying the association between morningness-eveningness and depression. They highlight the importance of morningness-eveningness modification to increase resilience and the need to consider anxiety jointly in this process.

Carbapenem-resistant Acinetobacter baumannii Outbreak in a COVID-19 Isolation Ward and Successful Outbreak Control with Infection Control Measures.

BACKGROUND: Even amid the coronavirus disease-19 (COVID-19) pandemic, the spread of multidrug-resistant bacteria and infection control are still important tasks. After recognizing the carbapenem-resistant Acinetobacter baumannii (CRAB) outbreak that occurred in the isolation room for COVID-19, we would like to introduce what infection control measures were implemented to eradicate it. MATERIALS AND METHODS: All COVID-19 patients with CRAB in any specimen admitted to the COVID-19 isolation ward of the tertiary hospital in Korea from October to November 2021 were analyzed. RESULTS: During the outbreak, 23 patients with COVID-19 and CRAB infections were identified. The index case was an 85-year-old female referred from a long-term care facility. CRAB was identified in sputum culture in most patients (91.3%). The CRAB outbreak occurred mainly in the rooms around the index case. Environmental cultures on the floor, air inlet, air outlet, and window frame of the rooms were performed. The antimicrobial resistance patterns of CRAB from patients and the environment were identical; whole-genome sequencing analyses revealed isolated clonality. Infection control measures with enhanced environmental cleaning using 1,000 ppm sodium hypochlorite and phenolic compounds, enhanced hand hygiene, additional education, and mandatory additional gowning and gloving of COVID-19 personal protective equipment (PPE) were applied on 29 October. No CRAB infection cases occurred from 2 November for two weeks. CONCLUSION: In addition to applying PPE and COVID-19 precautions in COVID-19 isolation wards, adhering to strict contact precautions along with environmental control can help prevent the spread of multidrug-resistant bacteria.

A Modified eCura System to Stratify the Risk of Lymph Node Metastasis in Undifferentiated-Type Early Gastric Cancer After Endoscopic Resection.

PURPOSE: The original eCura system was designed to stratify the risk of lymph node metastasis (LNM) after endoscopic resection (ER) in patients with early gastric cancer (EGC). We assessed the effectiveness of a modified eCura system for reflecting the characteristics of undifferentiated-type (UD)-EGC. MATERIALS AND METHODS: Six hundred thirty-four patients who underwent non-curative ER for UD-EGC and received either additional surgery (radical surgery group; n=270) or no further treatment (no additional treatment group; n=364) from 18 institutions between 2005 and 2015 were retrospectively included in this study. The eCuraU system assigned 1 point each for tumors >20 mm in size, ulceration, positive vertical margin, and submucosal invasion <500 µm; 2 points for submucosal invasion ≥500 µm; and 3 points for lymphovascular invasion. RESULTS: LNM rates in the radical surgery group were 1.1%, 5.4%, and 13.3% for the low- (0-1 point), intermediate- (2-3 points), and high-risk (4-8 points), respectively (P-for-trend<0.001). The eCuraU system showed a significantly higher probability of identifying patients with LNM as high-risk than the eCura system (66.7% vs. 22.2%; McNemar P<0.001). In the no additional treatment group, overall survival (93.4%, 87.2%, and 67.6% at 5 years) and cancer-specific survival (99.6%, 98.9%, and 92.9% at 5 years) differed significantly among the low-, intermediate-, and high-risk categories, respectively (both P<0.001). In the high-risk category, surgery outperformed no treatment in terms of overall mortality (hazard ratio, 3.26; P=0.015). CONCLUSIONS: The eCuraU system stratified the risk of LNM in patients with UD-EGC after ER. It is strongly recommended that high-risk patients undergo additional surgery.

Identification of New Pathogenic Variants of Hereditary Diffuse Gastric Cancer.

Purpose: Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression. Materials and Methods: Among 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing (WES) on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation and enrichment analysis were performed. Results: As a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the RhoaR129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked RhoAR129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families. Conclusion: The RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.

Effector Function Characteristics of Exhausted CD8+ T-cell in Microsatellite Stable and Unstable Gastric Cancer.

Purpose: Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors (ICIs), presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential. Materials and Methods: We explored the molecular characteristics of CD8+ T cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis. Results: In MSI-H gastric cancer, significantly higher proportions of effector memory T cell (Tem), exhausted T cell (Tex), proliferative exhausted T cell (pTex), and proliferative T cell were observed, while MSS gastric cancer exhibited significantly higher proportions of mucosal-associated invariant T (MAIT) cell and NKT cell. In MSI-H gastric cancer, Tex and pTex exhibited a significant upregulation of the exhaustion marker LAG3, as well as elevated expression of effector function markers such as IFNG, GZMB, GZMH, and GZMK, compared to those in MSS gastric cancer. The IFN-γ signaling pathway of Tex and pTex was retained compared to those of MSS gastric cancer. The spatial transcriptome analysis demonstrates the IFN-γ signaling pathway between neighboring Tex and malignant cell, showcasing a significantly elevated interaction in MSI-H gastric cancer. Conclusion: Our study reveals novel finding indicating that IFN-γ signaling pathway is retained in Tex and pTex of MSI-H gastric cancer, offering a comprehensive perspective for future investigations into immunotherapy for gastric cancer.

Stool protein mass spectrometry identifies biomarkers for the early detection of diffuse-type gastric cancer.

There is a high unmet need for early detection approaches for diffuse gastric cancer (DGC). We examined whether the stool proteome of mouse models of GC or individuals with hereditary diffuse GC (HDGC) have utility as biomarkers for early detection. Proteomic mass spectrometry of stool from a genetically engineered mouse model driven by oncogenic KrasG12D and loss of p53 and Cdh1 in gastric parietal cells (known as TCON mice) identified differentially abundant proteins compared to littermate controls. Immunoblot assays validated a panel of proteins including actinin alpha 4 (ACTN4), N-acylsphingosine amidohydrolase 2 (ASAH2), dipeptidyl peptidase 4 (DPP4), and valosin-containing protein (VCP) as enriched in TCON stool compared to littermate control stool. Immunofluorescence analysis of these proteins in TCON stomach sections revealed increased protein expression as compared to littermate controls. Proteomic mass spectrometry of stool obtained from HDGC patients with CDH1 mutations identified increased expression of ASAH2, DPP4, VCP, lactotransferrin (LTF), and tropomyosin-2 (TPM2) relative to stool from healthy sex and age-matched donors. Chemical inhibition of ASAH2 using C6-urea ceramide was toxic to GC cell lines and patient derived-GC organoids. This toxicity was reversed by adding downstream products of the S1P synthesis pathway, suggesting a dependency on ASAH2 activity in GC. An exploratory analysis of the HDGC stool microbiome identified features which correlated with patient tumors. Here we provide evidence supporting the potential of analyzing stool biomarkers for the early detection of DGC.

RNA expression of 6 genes from metastatic mucosal gastric cancer serves as the global prognostic marker for gastric cancer with functional validation.

BACKGROUND: Molecular analysis of advanced tumors can increase tumor heterogeneity and selection bias. We developed a robust prognostic signature for gastric cancer by comparing RNA expression between very rare early gastric cancers invading only mucosal layer (mEGCs) with lymph node metastasis (Npos) and those without metastasis (Nneg). METHODS: Out of 1003 mEGCs, all Npos were matched to Nneg using propensity scores. Machine learning approach comparing Npos and Nneg was used to develop prognostic signature. The function and robustness of prognostic signature was validated using cell lines and external datasets. RESULTS: Extensive machine learning with cross-validation identified the prognostic classifier consisting of four overexpressed genes (HDAC5, NPM1, DTX3, and PPP3R1) and two downregulated genes (MED12 and TP53), and enabled us to develop the risk score predicting poor prognosis. Cell lines engineered to high-risk score showed increased invasion, migration, and resistance to 5-FU and Oxaliplatin but maintained sensitivity to an HDAC inhibitor. Mouse models after tail vein injection of cell lines with high-risk score revealed increased metastasis. In three external cohorts, our risk score was identified as the independent prognostic factor for overall and recurrence-free survival. CONCLUSION: The risk score from the 6-gene classifier can successfully predict the prognosis of gastric cancer.

Nonsense-mediated mRNA decay of mRNAs encoding a signal peptide occurs primarily after mRNA targeting to the endoplasmic reticulum.

Translation of messenger ribonucleic acids (mRNAs) encoding integral membrane proteins or secreted proteins occurs on the surface of the endoplasmic reticulum (ER). When a nascent signal peptide is synthesized from the mRNAs, the ribosome-nascent chain complex (RNC) is recognized by the signal recognition particle (SRP) and then transported to the surface of the ER. The appropriate targeting of the RNC-SRP complex to the ER is monitored by a quality control pathway, a nuclear cap-binding complex (CBC)-ensured translational repression of RNC-SRP (CENTRE). In this study, using ribosome profiling of CBC-associated and eukaryotic translation initiation factor 4E-associated mRNAs, we reveal that, at the transcriptomic level, CENTRE is in charge of the translational repression of the CBC-RNC-SRP until the complex is specifically transported to the ER. We also find that CENTRE inhibits the nonsense-mediated mRNA decay (NMD) of mRNAs within the CBC-RNC-SRP. The NMD occurs only after the CBC-RNC-SRP is targeted to the ER and after eukaryotic translation initiation factor 4E replaces CBC. Our data indicate dual surveillance for properly targeting mRNAs encoding integral membrane or secretory proteins to the ER. CENTRE blocks gene expression at the translation level before the CBC-RNC-SRP delivery to the ER, and NMD monitors mRNA quality after its delivery to the ER.

Host size matters for reproduction: Evolution of spawning preference and female reproductive phenotypes in mussel-symbiotic freshwater bitterling fishes.

Bitterling fishes evolve an idiosyncratic symbiosis with freshwater mussels, in which they are obligated to spawn in the gills of mussels for reproduction. In recent years, freshwater mussel populations have been drastically diminishing, due to accelerating anthropogenic impacts, which can be large threats to the risk of bitterling's extinction cascade (i.e. 'coextinction'). The host mussel size may be an important factor driving the adaptation and evolution of bitterling's reproductive phenotypes. Here we examined the host size preference and morphological adaptation of female bitterling to the host size from 17 localities at the Han River in Korea. Using our developed molecular-based species identification for bitterling's eggs/larvae inside the mussels, we further determined the spawning patterns of seven bitterling species. Mean length of spawned mussels (N = 453) was significantly larger than that of unspawned mussels (N = 1814), suggesting that bitterling prefers to use larger hosts as a spawning ground. Spawning probability was clearly greater as mussel size increases. Results of our reciprocal transplant experiments do provide some evidence supporting the 'bitterling's larger host preference' hypothesis. Interspecific competition appeared to be intense as two fish species often spawned eggs in the same mussel individuals simultaneously. Longer ovipositor and more elongated egg may evolve in females of Tanakia signifer in response to larger host environments. The observed bitterling's spawning preference for large-sized mussels may evolve perhaps because of the fitness advantage in relation to the offspring survival. Our findings further inform on the development of effective conservation and management strategy for the endangered bitterling fishes.

The effect of glycosylated hemoglobin levels on the response to intravitreal dexamethasone implant for treating diabetic macular edema.

This study investigates the impact of glycosylated hemoglobin (HbA1c) on the efficacy of intravitreal dexamethasone (DEX) implants in patients with diabetic macular edema (DME) over a 12-month period. We retrospectively reviewed 90 DME patients treated with DEX implants, categorizing them based on baseline HbA1c levels (≤ 7% and > 7%) and 12-month changes in HbA1c ("improved", "stable", "worsened"). At the 2-month mark, the mean central subfield thickness (CST) reduction in the HbA1c ≤ 7% group was - 147.22 ± 113.79 µm compared to -130.41 ± 124.50 µm in the > 7% group (p = 0.506). Notably, 12-month outcomes between these groups showed no significant difference. The "improved" HbA1c subgroup experienced a more pronounced CST reduction at 2 months (p = 0.042), with outcomes leveling off with other groups by 12 months. Conclusively, DEX implant outcomes in DME were not influenced by either baseline HbA1c levels or their changes over time. This suggests that local alterations in the inflammation milieu may have a potentially stronger impact on DME treatment outcomes, highlighting the importance of considering local factors in DME treatment.

Detection of multiple recombinations of avian coronavirus in South Korea by whole-genome analysis.

Infectious bronchitis virus (IBV), an avian coronavirus, has caused considerable damage to the poultry industry. In Korea, indigenous KM91-like and newly introduced QX-like lineages belonging to the GI-19 lineage have been prevalent despite constant vaccination. In this study, complete genome sequences of 23 IBV isolates in Korea from 2010 to 2020 were obtained using next-generation sequencing, and their phylogenetic relationship and recombination events were analyzed. Phylogenetic analysis based on the S1 gene showed that all isolates belonged to the GI-19 lineage and were divided into five subgroups (KM91-like, K40/09-like, and QX-like II to IV). Among the 23 isolates, 14 recombinants were found, including frequent recombination between KM91-like and QX-like strains. In addition, it was observed that other lineages, such as GI-1, GI-13, and GI-16, were involved in recombination. Most recombination breakpoints were detected in the ORF1ab gene, particularly nsp3. However, when considering the size of each genome, recombination occurred more frequently in the 3a, E and 5a genes. Taken together, genetic recombination frequently occurred throughout the entire genome between various IBV strains in Korea, including live attenuated vaccine strain. Our study suggests the necessity of further research on the contribution of recombination of genomes outside the spike region to the biological characteristics of IBV.

Long-Term Outcome of Proximal Gastrectomy for Upper-Third Advanced Gastric and Siewert Type II Esophagogastric Junction Cancer Compared With Total Gastrectomy: A Propensity Score-Matched Analysis.

BACKGROUND: This study aimed to investigate the oncologic long-term safety of proximal gastrectomy for upper-third advanced gastric cancer (AGC) and Siewert type II esophagogastric junction (EGJ) cancer. METHODS: The study enrolled patients who underwent proximal gastrectomy (PG) or total gastrectomy (TG) with standard lymph node (LN) dissection for pathologically proven upper-third AGC and EGJ cancers between January 2007 and December 2018. Propensity score-matching with a 1:1 ratio was performed to reduce the influence of confounding variables such as age, sex, tumor size, T stage, N stage, and tumor-node-metastasis (TNM) stage. Kaplan-Meier survival analysis was performed to analyze oncologic outcome. The prognostic factors of recurrence-free survival (RFS) were analyzed using the Cox proportional hazard analysis. RESULTS: Of the 713 enrolled patients in this study, 60 received PG and 653 received TG. Propensity score-matching yielded 60 patients for each group. The overall survival rates were 61.7 % in the PG group and 68.3 % in the TG group (p = 0.676). The RFS was 86.7 % in the PG group and 83.3 % in the TG group (p = 0.634). The PG group showed eight recurrences (1 anastomosis site, 1 paraaortic LN, 1 liver, 1 spleen, 1 lung, 1 splenic hilar LN, and 2 remnant stomachs). In the multivariate analysis, the operation method was not identified as a prognostic factor of tumor recurrence. CONCLUSION: The patients who underwent PG had a long-term oncologic outcome similar to that for the patients who underwent TG for upper-third AGC and EGJ cancer.

Long-term impact of weight loss in people with class II obesity on the overall burden of disease: Evidence from the National Health Screening Cohort in Korea.

BACKGROUND: Obesity is known to increase overall disease burden but does obesity management actually help reduce disease burden? OBJECTIVES: To investigate the effects of weight loss on disease burden in people with obesity using the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) in Korea. SETTING: Pure longitudinal observational study using Nationwide cohort database. METHODS: Out of 514,866 NHIS-HEALS cohort, participants with class II obesity in Asia-Pacific region (30 ≤ body mass index [BMI] < 35) who underwent health check-up provided by NHIS during 2003-2004 (index date) were included. All final participants continued to receive a total of 5 biennial health check-ups over the next 10 years without missing. A group-based trajectory model (GBTM) was used to categorize subjects based on 10-year BMI change patterns. The changes of co-morbidities, healthcare resource utilization, and medical cost were analyzed. RESULTS: The final study subjects (9857) were categorized into 3 trajectory clusters based on the pattern of BMI (kg/m2) change: maintenance (57.35%) with an average change of -.02 ± .06, loss (38.65%) with -.04 ± .08, and substantial loss (4.0%) with -.10 ± .18. The annual increases in the number of co-morbidities per subject in each cluster were .18, .18, and .16 (all P < .001), respectively. The increase of healthcare resource utilization over time was lowest for the substantial loss compared to maintenance and loss. With each passing year, the average annual total healthcare cost increased by ₩21,200 ($16.48, P = .034) and ₩10,500 ($8.16, P = .498) in the maintenance and loss, respectively, but decreased by ₩62,500 ($48.59, P = .032) in the substantial loss. CONCLUSIONS: Weight loss in people with obesity was associated with a reduced burden of disease, as evidenced by lower co-morbidity, healthcare resource utilization rate, and decreased medical costs. This study highlights the potential positive long-term impact on Korean society when actively managing weight in individuals with obesity.

Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer.

Adding anti-programmed cell death protein 1 (anti-PD-1) to 5-fluorouracil (5-FU)/platinum improves survival in some advanced gastroesophageal adenocarcinomas (GEA). To understand the effects of chemotherapy and immunotherapy, we conducted a phase II first-line trial (n = 47) sequentially adding pembrolizumab to 5-FU/platinum in advanced GEA. Using serial biopsy of the primary tumor at baseline, after one cycle of 5-FU/platinum, and after the addition of pembrolizumab, we transcriptionally profiled 358,067 single cells to identify evolving multicellular tumor microenvironment (TME) networks. Chemotherapy induced early on-treatment multicellular hubs with tumor-reactive T-cell and M1-like macrophage interactions in slow progressors. Faster progression featured increased MUC5A and MSLN containing treatment resistance programs in tumor cells and M2-like macrophages with immunosuppressive stromal interactions. After pembrolizumab, we observed increased CD8 T-cell infiltration and development of an immunity hub involving tumor-reactive CXCL13 T-cell program and epithelial interferon-stimulated gene programs. Strategies to drive increases in antitumor immune hub formation could expand the portion of patients benefiting from anti-PD-1 approaches. SIGNIFICANCE: The benefit of 5-FU/platinum with anti-PD-1 in first-line advanced gastric cancer is limited to patient subgroups. Using a trial with sequential anti-PD-1, we show coordinated induction of multicellular TME hubs informs the ability of anti-PD-1 to potentiate T cell-driven responses. Differential TME hub development highlights features that underlie clinical outcomes. This article is featured in Selected Articles from This Issue, p. 695.