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Abstract Background Diffuse‐type gastric cancer (GC) is known to be more aggressive and relatively resistant to conventional chemotherapy. Hence, more optimized treatment strategy is urgently needed in diffuse‐type GC. Methods Using a panel of 10 GC cell lines and 3 GC patient‐derived cells (PDCs), we identified cell lines with high EMTness which is a distinct feature for diffuse‐type GC. We treated GC cells with high EMTness with ramucirumab alone, TGF‐β receptor kinase inhibitor (TEW‐7197) alone, or in combination to investigate the drug's effects on invasiveness, spheroid formation, EMT marker expression, and tumor‐induced angiogenesis using a spheroid‐on‐a‐chip model. Results Both TEW‐7197 and ramucirumab treatments profoundly decreased invasiveness of EMT‐high cell lines and PDCs. With a 3D tumor spheroid‐on‐a‐chip, we identified versatile influence of co‐treatment on cancer cell‐induced blood vessel formation as well as on EMT progression in tumor spheroids. The 3D tumor spheroid‐on‐a‐chip demonstrated that TEW‐7197 + ramucirumab combination significantly decreased PDC‐induced vessel formation. Conclusions In this study, we showed TEW‐7197 and ramucirumab considerably decreased invasiveness, thus EMTness in a panel of diffuse‐type GC cell lines including GC PDCs. Taken together, we confirmed that combination of TEW‐7197 and ramucirumab reduced tumor spheroid and GC PDC‐induced blood vessel formation concomitantly in the spheroid‐on‐a‐chip model.

In our ongoing search for new secondary metabolites from fungi, a basidiomycete fungus Irpex consors was selected for mycochemical investigation, and three new zwitterionic alkaloids (1-3) and five known compounds (4-8) were isolated from the culture broth (16 l) of I. consors. The culture filtrate was fractionated by a series of column chromatography including Diaion HP-20, silica gel, and Sephadex LH-20, Sep-Pak C18 cartridge, medium pressure liquid chromatography (MPLC), and high pressure liquid chromatography (HPLC) to yield eight compounds (1-8). The structures of the isolated compounds were elucidated by the interpretation of nuclear magnetic resonance (NMR) spectra and high-resolution mass spectrometry (HR-MS). Their antioxidant and antibacterial activities were examined. The zwitterionic structures of three new sesquiterpene alkaloids (1-3) were determined together with five known compounds identified as stereumamide E (4), stereumamide G (5), stereumamide H (6), stereumamide D (7), and sterostrein H (8). This is the first report of the zwitterionic alkaloids in the culture broth of I. consors. Three new zwitterionic alkaloids were named as consoramides A–C (1-3).

In our ongoing search for new secondary metabolites from fungal strains, one novel compound (1) and nine known compounds (2-10) were isolated from the EtOAc-soluble layer of the culture broth of Panus rudis. The culture broth of P. rudis was extracted in acetone and fractionated by solvent partition; column chromatography using silica gel, Sephadex LH-20, and Sephadex G-10; MPLC; and HPLC. The structures of isolated compounds were elucidated by one- and two-dimensional NMR and LC-ESI-mass measurements. One new compound, panepoxydiol (1), and nine known compounds, (E)-3-(3-hydroxy-3-methylbut-1-en-1-yl)-7-oxabicyclo[4.1.0]hept-3-ene-2,5-diol (2), isopanepoxydone (3), neopanepoxydone (4), panepoxydone (5), panepophenanthrin (6), 4-hydroxy-2,2-dimethyl-6-methoxychromane (7), 6-hydroxy-2,2-dimethyl-3-chromen (8), 2,2-dimethyl-6-methoxychroman-4-one (9), 3,4-dihydroxy-2,2-dimethyl-6-methoxychromane (10), were isolated from the culture broth of P. rudis. This is the first report of isolation of a new compound panepoxydiol (1) and nine other chemical constituents (2-5, 7-10) from the culture broth of P. rudis.

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.

Families are key in the healthy development of Latinx sexual minority youth (Latinx SMY), a group that experiences behavioral, mental, and sexual health disparities. Despite this, there are no family-based interventions for Latinx SMY and their families to prevent drug use, sexual risk behaviors, and depressive symptoms. The purpose of this pilot study was to evaluate the preliminary impact (i.e., estimated effect sizes) of "Familias con Orgullo" (FcO) and examine its feasibility and acceptability among 30 Latinx SMY and their parents. Parents and adolescents were randomized to FcO or a control condition and assessed pre/post-intervention. Feasibility was measured based on session completion and effect sizes. Focus groups were conducted to evaluate intervention acceptability. Findings showed promising effects favoring FcO on parent-adolescent communication (d = 0.46) and parental involvement (d = 0.34). There were also promising effects favoring FcO on suicidal thoughts (OR = 0.75) and depression symptoms (OR = 0.69). Finally, 100% of the adolescents in FcO either continued to remain drug-free or transitioned from current use to no use (from baseline to post-intervention) compared to 74% in the control. Effect sizes for condomless sex, parental monitoring, and positive parenting were small. Session completion (above 80%) and focus group findings indicated strong feasibility and acceptability. FcO holds promise for reducing drug use and depressive symptoms and improving family functioning among Latinx SMY.

Neuraminidase (NA) cleaves the glycosidic bond linkages of sialic acids to release the mature virions from infected cells and has been an attractive therapeutic target for anti-influenza agents. In our ongoing investigation of NA inhibitors in mushroom extracts, we found that the extract the fruiting body of Glaziella splendens potently inhibited neuraminidase. The fruiting bodies of G. splendens were extracted and partitioned successively with hexane, ethyl acetate, and butanol. The ethyl acetate soluble-layer was subjected to silica gel and Sephadex LH-20 column chromatographies, and MPLC to obtain five compounds (1–5). Their structures were determined by spectroscopic methods. NA inhibitory activity of these compounds was evaluated using NAs from recombinant rvH1N1, H3N2, and H5N1 influenza A viruses. One compound (1) was elucidated as a new azaphilone derivative, and four compounds (2–5) were identified as entonaemin A, comazaphilone D, rubiginosin A, and entonaemin B, respectively. Compounds 3 and 4 showed considerable inhibitory activity against three types of neuraminidases with the IC50 values of 30.9, 41.8, and 35.7 µM for 3 and 46.5, 50.4, and 29.9 µM for 4, respectively. This study reveals that the fruiting bodies of G. splendens possess azaphilone derivatives with the NA inhibitory activity. This is the first report on the isolation of neuraminidase inhibitors from the fruiting bodies of G. splendens.

Ulva lactuca (U. lactuca) is a green alga distributed worldwide and used as a food and cosmetic material. In our previous study, we determined the effects of U. lactuca methanol extracts on the UVB-induced DNA repair. In the present study, we fractionated U. lactuca methanol extracts to identify the effective compound for the DNA repair. MTT assay demonstrated that (+)-epiloliolide showed no cytotoxicity up to 100 μM in BJ-5ta human dermal fibroblast. Upon no treatment, exposure to UVB 400 J/m2 decreased cell viability by 45%, whereas (+)-epiloliolide treatment for 24 h after UVB exposure significantly increased the cell viability. In GO and GESA analysis, a number of differentially expressed genes were uniquely expressed in (+)-epiloliolide treated cells, which were enriched in the p53 signaling pathway and excision repair. Immunofluorescence demonstrated that (+)-epiloliolide increased the nuclear localization of p53. Comet assay demonstrated that (+)-epiloliolide decreased tail moment increased by UVB. Western blot analysis demonstrated that (+)-epiloliolide decreased the levels of p-p53, p21, Bax, and Bim, but increased that of Bcl-2. Reverse transcription PCR (RT-PCR) demonstrated that (+)-epiloliolide decreased the levels of MMP 1, 9, and 13, but increased that of COL1A1. These results suggest that (+)-epiloliolide regulates p53 activity and has protective effects against UVB.

Previous studies have suggested the impact of intervention fidelity on the management and prevention of chronic diseases; however, little is known about the effect of the contributing determinants (at multiple levels of influence) that can impact health-related interventions intending to improve the health status of Hispanic adolescents with overweight or obesity. The current study aimed to assess whether fidelity (i.e., dosage and quality of the program delivery), acculturation (i.e., orientation to the American culture, retention of Hispanic cultural values), and individual-level socio-demographic characteristics (i.e., income, education) predict changes in family processes (e.g., parent control), which in turn may affect adolescent health-related outcomes including body mass index (BMI), physical activity, dietary intake, and adolescents' health-related quality of life. A pathway analysis model was utilized to explore the study variables among 140 Hispanic parent-adolescent dyads randomized to Familias Unidas Health and Wellness (FUHW) intervention. Results indicated that fidelity was significantly associated with changes in parent-adolescent communication, parent monitoring, limit-setting, and control. Parents' education was associated with changes in parent limit-setting, and parent Hispanicism was associated with changes in parent limit-setting and discipline. The examination between family processes and adolescent health outcomes revealed that parents' higher discipline and improved communication with their adolescents were significantly associated with improved adolescents' quality of life, and parent control was positively associated with physical activity and negatively associated with BMI in adolescents. Our findings demonstrated the significant contribution of intervention fidelity and participants' characteristics in parenting strategies leading to adolescents' health outcomes to prevent obesity-related chronic diseases. Future research is needed to investigate the effect of environmental and organizational factors on the delivery of the intervention materials.

The gap in knowledge and information-seeking between high and low socioeconomic status (SES) has been well documented. This study extends this knowledge gap hypothesis to narrative persuasion in the context of parents' knowledge and information-seeking intention concerning adolescents' COVID-19 vaccination. It specifically tests if the gap is moderated by a message type (narrative vs. non-narrative). An online quasi-experiment, with a 2 (participants' education level: high vs. low) × 3 (message type: narrative vs. non-narrative vs. no-message) between-subject design, showed a main effect of education level (i.e., parents with a higher [vs. lower] education level rated a higher intention to seek information and provided more correct answers on questions about adolescents' COVID-19 vaccination) and an interaction between the two factors. The interaction showed that the gap between high- and low-education groups in information-seeking intention disappeared among those who read the narrative or non-narrative, and the gap in knowledge disappeared among those who read the narrative. Study findings suggest the utility of narratives in narrowing the gap in knowledge and information-seeking to improve parents' decisions on child vaccination.

While loneliness in our real lives is increasingly recognized as having dire physical, mental, and emotional consequences, cooperative games have been shown to build empathy and provide positive social impact. In this paper, the authors present “The Woods,” a local cooperative, mixed-reality game using augmented reality and 4-channel audio spatialization panning that provides players with face-to-face interactions in pursuit of a shared goal. This paper discusses the narrative, mechanical, and sonic components of the game, as well as the game’s development process and the players’ experiences. The goal of our team is to develop a narrative-driven AR game that promotes collaborative problem-solving and engages players in an emergent physical and digital experience.

In July 2023, cases of highly pathogenic avian influenza (HPAI) were reported at 2 shelters for stray cats in Seoul, South Korea. The cause of infection was suspected to be improperly sterilized raw food made from domestic duck meat, which was manufactured in South Korea. All viruses isolated from cats at the shelters and from the raw food belonged to HPAI A(H5N1) clade 2.3.4.4b. The gene constellation of all viruses was most similar to that of viruses isolated in Korea in November 2022. Of note, the viruses isolated from infected cats harbored mutations E627K or D701N in polymerase basic 2, which are indicative of adaptation to mammals. Postmortem examination revealed systemic pathologic lesions and the presence of widespread virus in different tissues. Thus, consumption of raw duck meat contaminated with HPAI virus likely caused systemic symptoms and death in cats, indicating the introduction of mammal-adapted mutations of the virus. [ABSTRACT FROM AUTHOR]

Active surveillance (AS) has been widely adopted as an alternative to immediate surgery owing to the indolent nature and favorable outcomes of papillary thyroid microcarcinoma PTMC). AS is generally recommended for tumors measuring ≤1 cm without aggressive cytological subtypes, risk of gross extrathyroidal extension (ETE), lymph node metastasis (LNM), or distant metastasis. AS requires careful patient selection based on various patient and tumor characteristics, and ultrasound (US) findings. Moreover, during AS, regular US is performed to monitor any signs of tumor progression, including tumor growth, new US features of potential gross ETE, and LNM. Therefore, appropriate imaging-based assessment plays a crucial role in determining whether AS or surgery should be pursued. However, detailed recommendations concerning US evaluation are currently insufficient, necessitating the formulation of this guideline. The Korean Society of Thyroid Radiology has developed a consensus statement for low-risk PTMC, covering US assessment methods when considering AS as a management option and conducting follow-up imaging tests during AS. This guideline aims to provide optimal scientific evidence and expert opinion consensus regarding a standardized US-based assessment protocol for low-risk PTMC. [ABSTRACT FROM AUTHOR]

Background: Idiopathic transverse myelitis (iTM) is defined as an inflammatory myelopathy of undetermined etiology, even after a comprehensive workup to identify other possible causes. Generally, the characteristics of recurrent iTM are not clearly defined. This study aimed to identify the clinical characteristics and predictive factors of recurrence in patients with iTM. Methods: We retrospectively recruited patients with transverse myelitis (TM) who visited Chungnam National University Hospital between January 2011 and December 2021. We included patients who were followed up for at least 2 years and excluded those diagnosed with multiple sclerosis or neuromyelitis optica spectrum disorder (NMOSD) during the initial episode or follow-up period. Patients with iTM were categorized into two groups: monophasic idiopathic TM (mTM) and recurrent idiopathic TM (rTM). We compared the clinical characteristics and spinal magnetic resonance imaging findings between the two groups. Results: In total, 167 patients were reviewed, of whom 112 were excluded. Finally, we included 55 patients with iTM. In 55 patients, 11 (20.0%) and 44 (80%) were classified into the rTM and mTM groups, respectively. Male predominance was observed in the iTM, rTM, and mTM groups. The percentage of patients with low vitamin D levels was significantly higher in the rTM group (100.0%) compared with the mTM group (70%) (p = 0.049). In addition, longitudinally extensive transverse myelitis (LETM) was observed more frequently in the rTM group, in 8 of 11 (72.7%) patients, compared with 15 of 44 (34.1%) patients in the mTM group, with the difference being statistically significant (p = 0.020). In multivariate regression analysis, female sex, younger age at onset, low serum vitamin D level (<30 ng/mL), and LETM were risk factors for recurrence. LETM was a significant predictor of relapse in iTM (p = 0.043, odds ratio = 13.408). Conclusion: In this study, the clinical features of mTM and rTM are nearly indistinguishable. In conclusion, >20% of the patients with iTM experience recurrence, and LETM is the most significant risk factor for recurrence. In cases of recurrence, there is a favorable response to immunotherapy, and the prognosis is generally good. Although LETM may be the initial symptom of NMOSD, it may be manifestation of iTM, and in cases of idiopathic LETM, it is important to be mindful of the elevated risk of recurrence. Based on these results, idiopathic rTM has good clinical prognosis and response to immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

The prevalence of highly pathogenic avian influenza (HPAI) A(H5N1) viruses has increased in wild birds and poultry worldwide, and concomitant outbreaks in mammals have occurred. During 2023, outbreaks of HPAI H5N1 virus infections were reported in cats in South Korea. The H5N1 clade 2.3.4.4b viruses isolated from 2 cats harbored mutations in the polymerase basic protein 2 gene encoding single amino acid substitutions E627K or D701N, which are associated with virus adaptation in mammals. Hence, we analyzed the pathogenicity and transmission of the cat-derived H5N1 viruses in other mammals. Both isolates caused fatal infections in mice and ferrets. We observed contact infections between ferrets, confirming the viruses had high pathogenicity and transmission in mammals. Most HPAI H5N1 virus infections in humans have occurred through direct contact with poultry or a contaminated environment. Therefore, One Health surveillance of mammals, wild birds, and poultry is needed to prevent potential zoonotic threats. [ABSTRACT FROM AUTHOR]

Introduction: Although the safety and effectiveness of COVID-19 vaccination during pregnancy have been proven, there is still little data explaining neonatal outcomes of maternal pre-pregnancy vaccination. Methods: Here, we investigated the impact of vaccination and SARS-CoV-2 infection on maternal-neonate immune response in a cohort study involving 141 pregnant individuals, and defined the importance of maternal COVID-19 vaccination timing for its effectiveness. Results and discussion: Our data indicate that vertically transferred maternal hybrid immunity provides significantly better antiviral protection for a neonate than either maternal post-infection or post-vaccination immunity alone. Higher neutralization potency among mothers immunized before pregnancy and their newborns highlights the promising role of pre-pregnancy vaccination in neonatal protection. A comparison of neutralizing antibody titers calculated for each dyad suggests that infection and pre-/during-pregnancy vaccination all support transplacental transfer, providing the offspring with strong passive immunity against SARS-CoV-2. Analysis of neutralizing antibody levels in maternal sera collected during pregnancy and later during delivery shows that immunization may exert a positive effect on maternal protection. [ABSTRACT FROM AUTHOR]

Latine university students represent 21.7% of the U.S. undergraduate student body, yet limited research explores their experiences with cultural stressors, self-esteem, and identity. This study examines the relationship between daily self-esteem and negative context of reception, moderated by two identity processes: normative identity style to host society and country of origin. Using multilevel models, we found that perceived negative context of reception one day predicts lower self-esteem the next day. Normative identity style to country of origin significantly moderated this relationship, exacerbating the impact, while normative style to host society showed no significant effect. These findings highlight the importance of identity processes in understanding self-esteem fluctuations among Latine students. [ABSTRACT FROM AUTHOR]

Highly pathogenic avian influenza H5N6 and H5N1 viruses of clade 2.3.4.4b were simultaneously introduced into South Korea at the end of 2023. An outbreak at a broiler duck farm consisted of concurrent infection by both viruses. Sharing genetic information and international surveillance of such viruses in wild birds and poultry is critical. [ABSTRACT FROM AUTHOR]

Background: This study investigated the impact of COVID-19 pandemic on the incidence and severity of myasthenia gravis (MG) using the National Health Insurance Service (NHIS) database in Korea. Methods: We analyzed data from patients with MG in the NHIS registry from 2015 to 2021. MG was defined as (1) patients aged ≥18 years with the G70.0 code, and (2) patients who visited tertiary hospitals regarldless of department in Korea (outpatient clinics at least twice or hospitalization at least once), and (3) patients who were prescribed pyridostigmine as MG medications at least once. We designated pre-COVID-19 as 2019 and post-COVID-19 as 2021 and analyzed the MG incidence and prevalence in 2019 and 2021. We compared the clinical data of patients with MG between the two years. MG exacerbation was defined as the administration of intravenous immunoglobulin or plasma exchange. Analysis of COVID-19 cases was conducted using an integrated database from the Korea Disease Control and Prevention Agency and NHIS. Patients with MG were divided into two groups according to COVID-19 status to compare their clinical characteristics. Results: A total of 6,888 and 7,439 MG cases were identified in 2019 and 2021, respectively. The standardized incidence was 1.56/100,000 in 2019, decreasing to 1.21/100,000 in 2021. Although the frequency of MG exacerbations was higher in 2019, there were no differences in the number and duration of hospitalizations, duration of ICU stays, hostalization expense, and mortality between 2019 and 2021. Patients with MG and COVID-19 had a higher frequency of MG exacerbations than patients without COVID-19, but there were no differences in the number and duration of hospitalizations, hospitalization expense, and mortality. Conclusion: This study was the first nationwide population-based epidemiological study of MG during COVID-19 pandemic in Korea. The incidence of MG decreased during COVID-19 pandemic, and the severity of MG was not affected by COVID-19. [ABSTRACT FROM AUTHOR]

The Korean Peninsula’s mountainous terrain poses challenges to effective water resource management. Notably, two significant river basins, North Han River and Imjin River basins, are essentially shared rivers originating in North Korea. After the construction of various dams in North Korea, billions of tons per year of water annually decreased from the upper reaches of these rivers of North Korea to South Korea. This study conducted an impact analysis on two major river basins affected by dam operations in North Korea. Both before and after the Imnam Dam operation, significant reduction (27.7%) in the average monthly inflow was observed, and the total release of the Hwacheon Dam in South Korea decreased by 40.2%. The analysis of instream flow indicated that the operation of dams in North Korea had a substantial impact on fulfilling instream flow requirements for dams located in North Han River and Imjin River basins. To ensure instream flow, this study pro)posed two plans. The first plan involved the utilization of existing dams in the North Han River basin, while the second plan suggested connecting the dams in North Korea, taking into account the shared rivers. [ABSTRACT FROM AUTHOR]

Purpose To compare the efficacy and safety of radiofrequency ablation (RFA) and ethanol ablation (EA) followed by RFA in treating mixed cystic and solid thyroid nodules. Materials and Methods We included 243 nodules from 243 patients who underwent RFA for mixed cystic and solid benign nodules. The nodules were divided into two groups (RFA alone and EA + RFA). We evaluated volume reduction rate (VRR), therapeutic success rate, improvement in symptomatic and cosmetic issues, complications, and adverse effects. Results The RFA group included 204 patients, and the EA + RFA group included 39 patients. The long-term success rates in the RFA only and EA + RFA groups were 90.2% and 97.4%, respectively. The mean VRR at the last follow-up in the RFA and EA + RFA groups were 81.6% and 87.2%, respectively. Therapeutic results were similar in both groups at the last followup. Cosmetic and symptomatic problems markedly improved in both groups. No major complications were observed. Conclusion Both RFA alone and EA + RA are safe and effective methods for treating mixed cystic and solid thyroid nodules, although EA + RFA is slightly more effective. [ABSTRACT FROM AUTHOR]