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Bisphenol A-glycidyl methacrylate (BisGMA) is a methacrylate monomer that is mainly used in three-dimensional structures to reconstruct dental and bony defects. BisGMA has toxic and proinflammatory effects on macrophages. Rutin is a natural flavonol glycoside that is present in various plants and has useful biological effects, such as anti-inflammatory, anticancer, and antioxidative effects. The aim of this study was to investigate the anti-inflammation of rutin in macrophages after exposure to BisGMA. Pretreatment of the RAW264.7 macrophage with rutin at 0, 10, 30, and 100 μM for 30 min before being incubated with BisGMA at 0 or 3 μM. Proinflammatory cytokines and prostaglandin (PG) E2 were detected by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was detected by the Griess assay. Expression and phosphorylation of proteins were measured by Western blot assay. Pretreatment with rutin inhibited the BisGMA-induced generation of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and PGE2, in macrophages. Rutin also suppressed the BisGMA-induced secretion of NO and expression of inducible nitric oxide synthase (iNOS) in a concentration-dependent manner. Furthermore, rutin suppressed the mitogen-activated protein kinase (MAPK) phosphorylation in a concentration-dependent manner. Finally, rutin suppressed the BisGMA-induced phosphorylation of nuclear factor (NF)-κB p65 and degradation of inhibitor of κB (IκB). These results indicate that the concentration of rutin has an inhibitory effect on proinflammatory mediator generation, MAPK phosphorylation, NF-κB p65 phosphorylation, and IκB degradation. In conclusion, rutin is a potential anti-inflammatory agent for BisGMA-stimulated macrophages through NF-κB p65 phosphorylation and IκB degradation resulting from MAPK phosphorylation.

LMB-100 is a novel immune-conjugate (immunotoxin) that targets mesothelin. A phase 1/2 clinical trial was conducted (NCT02810418) with primary objectives assessing the safety and efficacy of LMB-100 ± nab-paclitaxel. Participant blood samples were analyzed for changes in serum cytokines and circulating immune cell subsets associated with response or toxicity. On Arm A, participants (n = 20) received standard 30-minute LMB-100 infusion with nab-paclitaxel. Although clinical efficacy was observed, the combination caused intolerable capillary leak syndrome (CLS), a major toxicity of unclear etiology that affects many immunotoxin drugs. Participants developing CLS experienced rapid elevations in IFNγ and IL-8 compared to those without significant CLS, along with midcycle increases in Ki-67- CD4 T cells that were CD38, HLA-DR, or TIM3 positive. Additionally, a strong increase in activated CD4 and CD8 T cells and a concurrent decrease in Tregs were seen in the single Arm A patient achieving a partial response. In Arm B, administration of single agent LMB-100 to participants (n = 20) as a long infusion given over 24-48 h was investigated based on pre-clinical data that this format could reduce CLS. An optimal dose and schedule of long infusion LMB-100 were identified, but no clinical efficacy was observed even in patients receiving LMB-100 in combination with nab-paclitaxel. Despite this, both Arm A and B participants experienced increases in specific subsets of proliferating CD4 and CD8 T cells following Cycle 1 treatment. In summary, LMB-100 treatment causes systemic immune activation. Inflammatory and immune changes that accompany drug associated CLS were characterized for the first time.

Understanding the factors that influence trust in public health information is critical for designing successful public health campaigns during pandemics such as COVID-19. We present findings from a cross-sectional survey of 454 US adults-243 older (65+) and 211 younger (18-64) adults-who responded to questionnaires on human values, trust in COVID-19 information sources, attention to information quality, self-efficacy, and factual knowledge about COVID-19. Path analysis showed that trust in direct personal contacts (

Saeu-jeot, or shrimp paste, is a traditional Korean high-salt fermented seafood. This study elucidated the effects of saeu-jeot extract (SJE) on NLRP3 inflammasome activation and radiation-induced micronucleus formation.We treated lipopolysaccharide-primed mouse bone marrow-derived macrophages with the NLRP3 inflammasome activators ATP and nigericin. We also analyzed the acute effects of ionizing radiation on micronucleated polychromatic erythrocytes (MnPCEs) in whole-body gamma-irradiated male BALB/c and C57BL/6 mice after oral administration of SJE.SJE significantly inhibited NLRP3 inflammasome activation, reducing IL-1β secretion in vitro. In addition, the frequency of MnPCEs was significantly lower in SJE-treated mice.SJE has anti-inflammatory effects and reduces radiation-induced chromosome damage.

The phase reconstruction process in digital holographic microscopy involves a trade-off between the phase error and the high-spatial-frequency components. In this reconstruction process, if the narrow region of the sideband is windowed in the Fourier domain, the phase error from the DC component will be reduced, but the high-spatial-frequency components will be lost. However, if the wide region is windowed, the 3D profile will include the high-spatial-frequency components, but the phase error will increase. To solve this trade-off, we propose the high-variance pixel averaging method, which uses the variance map of the reconstructed depth profiles of the windowed sidebands of different sizes in the Fourier domain to classify the phase error and the high-spatial-frequency components. Our proposed method calculates the average of the high-variance pixels because they include the noise from the DC component. In addition, for the nonaveraged pixels, the reconstructed phase data created by the spatial frequency components of the widest window are used to include the high-spatial-frequency components. We explain the mathematical algorithm of our proposed method and compare it with conventional methods to verify its advantages.

To overcome the limitations in the use of protein as an emulsifier, soy lecithin, a natural surfactant, was used along with whey protein isolate (WPI) to produce o/w emulsions containing cholecalciferol and α-tocopherol. The physical stability of the emulsions prepared with WPI and varying concentrations of lecithin (0, 1, 2, and 3% w/w) was measured in different heat, pH, and ionic-strength food environmental conditions.All emulsions were shown to be less than 250 nm in size and less than 0.3 in polydispersity index (PDI). The morphology of the emulsions was spherical, and the droplets of the emulsion containing lecithin were thicker and larger than those of the emulsion without lecithin (WPI_L0). After autoclaving, WPI_L0 increased in size from 197.8 ± 1.7 nm to 528.5 ± 28.4 nm, and the retention of cholecalciferol and α-tocopherol decreased to 40.83 ± 0.63% and 49.68 ± 1.84%, respectively. At pH 5.5, near the isoelectric point of WPI, WPI_L0 increased in size due to aggregation, but emulsions containing lecithin remained stable at a PDI under 0.3. Turbiscan stability index of the emulsion prepared with WPI and 3% lecithin was the lowest, indicating good storage stability. In addition, it was confirmed that the higher the lecithin content, the higher the viscosity, and the higher the amount of free fatty acids released in the in vitro digestion model.This study can provide theoretical evidence for enhancing the physical stability of protein emulsions by co-stabilization with lecithin, promoting their application in various foods. © 2022 Society of Chemical Industry.

MicroRNAs are reported as promising biomarkers for the diagnosis and treatment of breast cancer. miR-1260b is identified as a tumor-associated noncoding microRNA in other cancers, although the role of miR-1260b and its clinical relevance in breast cancer remain unclear. In this study, miR-1260b as a potential prognostic biomarker was observed by univariate and multivariate Cox regression analyses in 102 breast tumor tissues. The tumorigenic role of miR-1260b in terms of proliferation, apoptosis, and migration of breast cancer cells was investigated using gain- and loss-of-function assays in vitro. Additionally, the potential early diagnosis and treatment monitoring marker of miR-1260b was validated in 129 plasma samples. We found that high miR-1260b expression was markedly associated with bulky tumor size, advanced stage, and lymph node invasion. Particularly, the high-miR-1260b-expression group showed shorter overall survival than the low-miR-1260b-expression group. The inhibition of oncogenic miR-1260b induced apoptosis and decreased migration and invasion of MDA-MB-231 cells. CASP8 was revealed as a direct target gene of miR-1260b, which is closely related to apoptosis. Furthermore, miR-1260b expression levels in plasma were significantly higher in patients with breast cancer than in healthy controls. The patients who tested positive for miR-1260b showed 16.3- and 18.2-fold higher risks in the early stage and locally advanced stage, respectively, compared with healthy controls, and the risk was decreased 6.2-fold after neoadjuvant chemotherapy. Taken together, miR-1260b may be a potential novel diagnostic, prognostic, and therapeutic target in breast cancer.

The RING domain of MUL1 (RING

The FAT1 gene functions as a tumor suppressor or promoter and remains incompletely understood. We examined the clinical significance of FAT1 in head and neck squamous cell carcinoma (HNSCC) using four publicly available HNSCC cohorts and one HNSCC cohort enrolled at a tertiary medical center. We developed FAT1 signatures reflecting FAT1 mutations and mRNA expression using one cohort. Patients with HNSCC were classified into FAT1-associated low risk (FAT1-LR; n = 195) and FAT1-associated high risk (FAT1-HR; n = 371) subgroups. The five-year overall survival and recurrence-free survival rates were significantly lower in the FAT1-HR subgroup than in the FAT1-LR subgroup (P = 0.01 and 0.003, respectively). The clinical significance of FAT1 was validated using four independent cohorts. Cox proportional hazards models showed that the FAT1 signature was an independent prognostic factor for HNSCC patients. In addition, FAT1 signature was associated with the response to radiotherapy, advanced stage, and human papilloma virus (HPV) status in HNSCC patients. In conclusion, the FAT1 gene signature was associated with prognosis of HNSCC and may help to provide personalized treatments for HNSCC patients.

Background Studies on the application of targeted therapies for patients with non‐small cell lung cancer (NSCLC) who harbor rare genetic mutations are ongoing. In the present study, we investigated the real‐world data of NSCLC patients who harbor rare mutations. Methods We retrospectively analyzed patients with advanced or metastatic nonsquamous NSCLC aged >20 years with confirmed rare mutations (BRAF, ROS1, MET, RET, HER2, FGFR, and NTRK) from January 2015 to September 2020 at nine tertiary hospitals. In addition, we validated the lung cancer PCR panel kit in patients with confirmed mutations by NGS. Results Among 118 patients included, 88 received platinum‐based chemotherapy as first‐line chemotherapy. The progression‐free survival of patients with BRAF, ERBB2, MET, RET, and ROS1 mutations was 10.9 months (95% confidence interval [CI]: 1.3–20.5), 5.3 months (95% CI: 3.0–7.5), 7.2 months (95% CI: 3.6–10.9), 11.4 months (95% CI: 9.2–13.6), and 10.0 months (95% CI: 3.7–16.4) respectively (p = 0.041). The median overall survival (OS) was not reached in patients with ROS1 mutations; however, in BRAF, ERBB2, MET, and RET mutant patients, median OS was 14.1 months (95% CI: 10.1–14.1), 34.5 months (95% CI: 13.2–36.9), 22.7 months (95% CI: 1.7–24.0), and 29.8 months (95% CI: 28.9–61.3), respectively (p = 0.006). Of the 27 tissue samples, 26 (96.3%) showed the same PCR panel kit result with NGS. Conclusions First‐line platinum‐based chemotherapy showed durable benefit in patients with advanced or metastatic nonsquamous NSCLC harboring rare genetic mutation other than EGFR or ALK., This study shows real‐world data of NSCLC patients with rare genetic mutations, and the majority of patients were treated primarily with platinum‐based chemotherapy. First‐line platinum‐based chemotherapy showed durable benefit in patients with advanced or metastatic nonsquamous NSCLC harboring rare genetic mutations other than EGFR or ALK.

Investigation of phytochemicals in Prunus davidiana fruits led to the isolation of 13 phenolic compounds: five flavonoids ( 1 - 5 ), four phenylpropanoids ( 6-9 ), two lignans ( 10 and 11 ), one benzoic glycoside ( 12 ), and one cyanobenzyl glycoside ( 13 ). All phenolic compounds were reported for the first time from P. davidiana fruits in this study. The chemical structures of 1 - 13 were decided using various spectroscopic analyses such as MS, IR, and NMR. As well, the occurrence of the isolated ones in Prunus species was discussed. All compounds were evaluated for radical scavenging activity using ABTS and DPPH radicals. Compounds 2 , 5 , 6 , 8 , 9 , and 11 had much higher scavenging activity than ascorbic acid, a well-known antioxidant.

Background and aims Bile acid (BA) dysregulation is related to not only metabolic diseases but also nonalcoholic fatty liver disease (NAFLD). We investigated whether circulating BA levels are altered according to the histological severity of NAFLD independent of metabolic derangements. Methods Global metabolic profiling and targeted BA analysis using sera collected from biopsy-proven no-NAFLD (n = 67), nonalcoholic fatty liver (NAFL) (n = 99), and nonalcoholic steatohepatitis (NASH, n = 75) subjects were performed sequentially. Circulating metabolome analysis integrated with the hepatic transcriptome was performed to elucidate the mechanistic basis of altered circulating BA profiles after stratification by obesity (body mass index ≤ 25 kg/m2 ). Circulating BA alterations were also validated in an independent validation cohort (29 no-NAFLD, 70 NAFL and 37 NASH). Results Global profiling analysis showed that BA was the metabolite significantly altered in NASH compared to NAFL. Targeted BA analysis demonstrated that glyco-/tauro-conjugated primary BAs were commonly increased in nonobese and obese NASH, while unconjugated primary BAs increased only in nonobese NASH. These characteristic primary BA level changes were maintained even after stratification according to diabetes status and were replicated in the independent validation cohort. Compared to nonobese NAFL patients, nonobese NASH patients exhibited upregulated hepatic expression of CYP8B1. Conclusions BA metabolism is dysregulated as the histological severity of NAFLD worsens, independent of obesity and diabetes status; dysregulation is more prominent in nonobese NAFLD patients. Metabolome-driven omics approach provides new insight into our understanding of altered BA metabolism associated with individual phenotypes of NAFLD.

We compared the diagnostic accuracies of narrowband imaging and white-light endoscopy in the detection of nasopharyngeal cancer.Six databases (PubMed, Cochrane Database, Embase, Web of Science, SCOPUS, and Google Scholar).The 6 databases were thoroughly reviewed by 2 authors (working independently) from their dates of inception to December 2019. Nasopharyngeal mucosal or vascular changes detected by narrowband imaging were compared to those detected by white-light endoscopy. The authors extracted true-positive, true-negative, false-positive, and false-negative parameters for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. The extent of interrater agreement was assessed.Eighteen prospective or retrospective studies were included. The diagnostic odds ratio of narrowband imaging was 77.560 (95% confidence interval [CI], 37.424-160.739). The area under the summary receiver operating characteristic curve was 0.926. The sensitivity, specificity, and negative predictive value were 0.871 (95% CI, 0.808-0.915), 0.905 (95% CI, 0.816-0.953), and 0.955 (95% CI, 0.906-0.979), respectively. The correlation between sensitivity and the false-positive rate was 0.284, indicating that heterogeneity was absent. Narrowband imaging exhibited moderate interrater reliability (0.7037; 95% CI, 0.6558-0.746). Subgroup analysis showed that vascular patterns revealed by endoscopy in a screened subgroup were significantly more diagnostically accurate than mucosal patterns used for surveillance of a recurrent cancer subgroup.Narrowband imaging exhibits high diagnostic accuracy and should be used in the diagnostic workup of nasopharyngeal cancer. However, further studies are necessary to confirm our results.

This study investigated whether current state‐of‐the‐art deep reasoning network analysis on psychometry‐driven diffusion tractography connectome can accurately predict expressive and receptive language scores in a cohort of young children with persistent language concerns (n = 31, age: 4.25 ± 2.38 years). A dilated convolutional neural network combined with a relational network (dilated CNN + RN) was trained to reason the nonlinear relationship between “dilated CNN features of language network” and “clinically acquired language score”. Three‐fold cross‐validation was then used to compare the Pearson correlation and mean absolute error (MAE) between dilated CNN + RN‐predicted and actual language scores. The dilated CNN + RN outperformed other methods providing the most significant correlation between predicted and actual scores (i.e., Pearson's R/p‐value: 1.00/, This study investigated whether current state‐of‐the‐art deep reasoning network analysis on psychometry‐driven diffusion tractography connectome can accurately predict expressive and receptive language scores in a cohort of young children with persistent language concerns. A dilated convolutional neural network combined with a relational network (dilated CNN+RN) was trained to reason the nonlinear relationship between “dilated CNN features of language network” and “clinically acquired language score.” The proposed dilated CNN+RN using psychometry‐driven diffusion tractography connectome may be useful for prediction of the presence, severity, and type of language disorder, and possibly provide a better understanding of the neurological mechanisms of language deficits in young children.

Background Because of the growing number of actionable biomarkers in non-small cell lung cancer (NSCLC), sufficient tissue availability for testing is becoming a greater challenge. Liquid biopsy offers a potential solution by complementing standard tissue-based methods. In this study, the authors analyzed the concordance of actionable genomic alterations sequenced from circulating tumor DNA (ctDNA; Guardant360) and tissue (Oncomine Focus Assay). Methods From September 2015 to May 2018, 421 paired plasma and tissue samples from patients with advanced NSCLC who had previously undergone tissue testing by standard methods were collected. Both types of samples were available for 287 patients (262 in cohort 1 [treatment-naive] and 25 in cohort 2 [treatment failure]), and only 1 sample type was available for 134 patients (50 in cohort 3 [plasma only] and 84 in cohort 4 [tissue only]). Results In cohort 1, 198 samples (77.6%) showed concordance between tissue and plasma next-generation sequencing (NGS). Among the discordant cases, plasma testing detected additional genomic alterations in 11 patients (4.2%). In 50 patients without tissue-based NGS results (cohort 3), the ctDNA-based test detected genomic alterations in 20 samples (40.0%). The median allele frequency (AF) of mutations identified with ctDNA-based NGS (0.74%) was lower than that identified with the tissue-based NGS test (13.90%). Clinical responses to matched targeted therapy occurred, regardless of the ctDNA AF. Upfront ctDNA-based testing identified 60.4% of patients with genomic alterations. In addition, ctDNA-based testing uncovered 12.0% more actionable alterations when it was performed after tissue-based NGS testing. Conclusions The results indicate that a ctDNA-based test identifies additional patients with actionable genomic alterations and could, therefore, be used to complement traditional tissue-based testing for NSCLC. Lay summary Circulating tumor DNA (ctDNA)-based next-generation sequencing (NGS) testing is becoming essential as the number of actionable genomic biomarker increases for the treatment selection of non-small cell lung cancer. This study demonstrates the additive value of ctDNA-based testing in addition to tissue-based NGS and standard of care-based biomarker testing for detecting additional patients with actionable genomic alterations. Clinical responses have also been observed in patients with a low allele frequency detected by ctDNA-based NGS testing.

OBJECTIVE Data regarding the prevalence of depression and anxiety among cancer patients, especially before cancer diagnosis, remains scarce. This study investigated the prevalence of these conditions and associated drug use among cancer patients pre- and post-diagnosis. METHODS This population-based cohort study using data from Taiwan's National Health Insurance Research Database recruited patients with a registered cancer diagnosis and matched control between January 1, 2000, and December 31, 2011. We compared the prevalence of anxiety and depressive disorders between cancer patients and non-cancer participants during a 2-year period both pre- and post-diagnosis by Pearson's chi-square test. Psychiatric medication use was also examined for the associated mental condition. RESULTS We examined participants diagnosed with liver (N = 17,154), colorectal (N = 30,391), breast (N = 40,036), gynecological (N = 23,218), and lung (N = 15,671) cancer. Before the cancer diagnosis, the prevalence of depression was higher in non-cancer participants than in gynecological cancer patients (p = 0.018) but anxiety is higher in liver, colorectal, and lung cancer patients when compared to non-cancer participants (p