Assessing venous invasion in stage II colon cancer: optimal elastin stains and survival analysis.

AIMS: Venous invasion (VI) in colorectal carcinoma influences treatment strategies, especially in early stages. Despite elastin staining effectiveness in detecting VI, guidelines for its routine application, including the optimal number of slides for staining, are limited. METHODS: Elastin staining was performed for VI assessment in patients with colorectal adenocarcinoma. Patients were categorised into two groups: single elastin stain group (SEG, n=248) and multiple elastin stain group (MEG, n=204). RESULTS: The average number of elastin-stained blocks was 2±1.7, increasing to 3.3±1.9 in MEG. VI detection was significantly higher in patients in MEG (50.5%) compared with SEG (37.0%) (p=0.004). VI detection rate was higher in MEG (63.7%) than in SEG (46.0%) among patients with stage III-IV disease (p=0.011), but did not significantly differ among patients with stage I-II disease. Staining two blocks improved VI detection without additional gains from more stains. Compared with elastin performed on a single block, VI detected by elastin stain on two or more blocks did not significantly impact progression-free or disease-free survival with stage II patients. CONCLUSIONS: Employing two elastin stains on separate blocks significantly enhances VI detection in colorectal carcinoma without additional benefits from more extensive staining. This study suggests that while increasing sensitivity for VI detection, staining beyond two blocks may not benefit prognostication and could be counterproductive, warranting further research. We emphasise the need for strategic use of the elastin stain and cautious interpretation of the increased detection sensitivity of multiple elastin stains.

ß2-microglobulin expression is associated with aggressive histology, activated tumor immune milieu, and outcome in colon carcinoma.

OBJECTIVES: We sought to assess the expression of human leukocyte antigen (HLA) proteins and ß2-microglobulin (B2M) in tumor cells and the relationship with immune microenvironment and outcome in colorectal cancer (CRC). METHODS: A total of 953 CRC cases were evaluated by immunohistochemistry for HLA class I, HLA class II, and B2M. The expression level of these biomarkers was correlated with clinicopathologic information, BRAF V600E and mismatch repair (MMR) proteins, and the quantitated expression levels of immune cells (CD8 and CD163) and immune regulatory proteins (FoxP3, programmed cell death 1 ligand 1 [PD-L1], and LAG3). RESULTS: We found that B2M-low tumors were statistically correlated with aggressive histologic features, including higher stage, higher grade, extramural venous invasion, perineural invasion, and distant metastasis. Expression of B2M was positively correlated (R2 = 0.3) and significantly associated with MMR-deficient tumors (P < .001); B2M-low tumors were also associated with an "immune cold"' microenvironment, including a reduced number of immune cells (CD8 and CD163), reduced expression of immune regulatory proteins by immune cells (PD-L1, FoxP3, and LAG3), and reduced tumor cell expression of PD-L1. These B2M-low tumors correlated with lower disease-specific survival (P = .018), a finding that maintained significance only for the proficient MMR cohort (P = .037). CONCLUSIONS: Our findings suggest that B2M expression may support predictive models for both outcome and checkpoint inhibitor therapy treatment response for colorectal adenocarcinoma.

Epithelial-mesenchymal transition induced by tumor cell-intrinsic PD-L1 signaling predicts a poor response to immune checkpoint inhibitors in PD-L1-high lung cancer.

BACKGROUND: We investigated the role of tumor cell-intrinsic PD-L1 signaling in the epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC) and the role of EMT as a predictive biomarker for immune checkpoint inhibitor (ICI) therapy. METHODS: PD-L1-overexpressing or PD-L1-knockdown NSCLC cells underwent RNA-seq and EMT phenotype assessment. Mouse lung cancer LLC cells were injected into nude mice. Two cohorts of patients with NSCLC undergoing ICI therapy were analyzed. RESULTS: RNA-seq showed that EMT pathways were enriched in PD-L1-high NSCLC cells. EMT was enhanced by PD-L1 in NSCLC cells, which was mediated by transforming growth factor-ß (TGFß). PD-L1 promoted the activation of p38-MAPK by binding to and inhibiting the protein phosphatase PPM1B, thereby increasing the TGFß production. Tumor growth and metastasis increased in nude mice injected with PD-L1-overexpressing LLC cells. In the ICI cohort, EMT signature was higher in patients with progressive disease than in those with responses, and EMT was significantly associated with poor survival in PD-L1-high NSCLC. In PD-L1-high NSCLC, EMT was associated with increased M2-macrophage and regulatory T-cell infiltrations and decreased cytotoxic T-cell infiltration. CONCLUSIONS: Tumor cell-intrinsic PD-L1 function contributes to NSCLC progression by promoting EMT. EMT may predict an unfavorable outcome after ICI therapy in PD-L1-high NSCLC.

Changes in the choice motive and emotional perception of chocolates in response to stress.

Although chocolates are often chosen for sensory pleasure, they are also selected to enhance mood and relieve emotional stress, or potentially chosen for its perceived health benefits if stress adversely affects physical well-being. This study aimed to investigate whether emotional stress influenced the motivations behind chocolate selection, subsequent liking, and emotional response. Participants were divided into a control group (n = 76) and a group with induced acute stress (n = 74). Stimuli were presented as dark chocolate packaging, each evoking sensory appeal, health, and emotional stress relief. Participants chose one stimulus from three options that they were most inclined to consume and evaluated the overall liking and emotional attributes of the stimuli. They also rated the overall liking and emotional attributes of three types of chocolates, each identical but paired with distinct stimuli. Their food attitudes were also assessed. Stress did not change the choice of stimuli, indicating that stress did not influence the motivation for chocolate selection. Instead, the choice of stimuli aligned with participants' food attitudes; those favoring sensory appeal and emotional stress relief prioritized pleasure in their usual food choices. Stress tended to increase liking and chocolate-associated positive emotions with sensory appeal, as opposed to others, to immediately alleviate negative emotions. The most robust motivation to consume chocolates was sensory pleasure, irrespective of stress, because of a preestablished association between sensory pleasure and mood enhancement.

Assessment of zinc, manganese, copper, and magnesium intake levels in Koreans using the Korean Total Diet Study.

This study evaluated zinc, manganese, copper, and magnesium intake levels in Koreans using the Korean Total Diet Study, targeting 92-93% of the Korean diet. Representative foods were collected from 9 cities, resulting in 1344-1368 samples. Results showed adequate intake for most minerals, but high proportions of adults and adolescents didn't meet recommended levels. Infants had high levels of zinc and manganese intake, posing possible health concerns. This is the first comprehensive assessment of these nutrients in Korea and is significant for considering all age groups, including infants, by analyzing nutrient content for table-ready (cooked) samples of foods. It is hoped that the Korean Total Diet Survey will be expanded to assess a wider range of nutrients for better nutrient intake assessment in Korea. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01394-y.

Metal-enhanced fluorescence biosensor integrated in capillary flow-driven microfluidic cartridge for highly sensitive immunoassays.

Point-of-care testing (POCT) for low-concentration protein biomarkers remains challenging due to limitations in biosensor sensitivity and platform integration. This study addresses this gap by presenting a novel approach that integrates a metal-enhanced fluorescence (MEF) biosensor within a capillary flow-driven microfluidic cartridge (CFMC) for the ultrasensitive detection of the Parkinson's disease biomarker, aminoacyl-tRNA synthetase complex interacting multi-functional protein 2 (AIMP-2). Crucial point to this approach is the orientation-controlled immobilization of capture antibody on a nanodimple-structured MEF substrate within the CFMC. This strategy significantly enhances fluorescence signals without quenching, enabling accurate quantification of low-concentration AIMP-2 using a simple digital fluorescence microscope with a light-emitting diode excitation source and a digital camera. The resulting platform exhibits exceptional sensitivity, achieving a limit of detection in the pg/mL range for AIMP-2 in human serum. Additionally, the CFMC design incorporates a capillary-driven passive sample transport mechanism, eliminating the need for external pumps and further simplifying the detection process. Overall, this work demonstrates the successful integration of MEF biosensing with capillary microfluidics for point-of-care applications.

Lymphoglandular Complex-Like Colorectal Carcinoma-A Series of 20 Colorectal Cases, Including Newly Reported Features of Malignant Behavior.

Distinguishing colon carcinoma that is surrounded by well-circumscribed lymphoid tissue from adenomas involving lymphoglandular complexes can be difficult. We assessed a multi-institutional international cohort of 20 colorectal carcinomas with associated prominent lymphoid infiltrates, which we referred to as lymphoglandular complex-like carcinoma (LGCC). We collected clinical and endoscopic features, including lesion size, endoscopic appearance, location, procedure, follow-up, AJCC stage, and mismatch repair status. We recorded the presence of the following histologic features: haphazard gland distribution, gland angulation, gland fusion, solid nest formation, single-cell formation, stromal desmoplasia, presence of lymphovascular invasion and perineural invasion, presence of lamina propria, cytologic atypia as low- or high-grade, presence of goblet cells in the invasive component, and the presence of a surface lesion. Most cases (9 of 13) were described endoscopically as sessile polyps with an average size of 1.56 cm. Most cases (90%) were associated with a surface lesion, of which the majority were tubular adenomas, though a subset was associated with sessile serrated lesions with dysplasia (3 of 18). All cases of LGCC demonstrated haphazard gland distribution and either gland angulation, fusion, or solid nest formation. A portion of cases demonstrated single-cell infiltration (35%) and desmoplasia (50%), and rarely lymphovascular invasion was present (5%). A subset (10%) of cases invaded beyond the submucosa. Deficient mismatch repair was present in 22% (2 of 9) of cases for which it was performed. In cases of colectomy or completion colectomy, nodal metastasis was present in 38% (3 of 8). No cases demonstrated disease recurrence or disease-specific mortality. Overall, LGCC represents an enigmatic subset of carcinomas that is important to distinguish from adenomas involving lymphoglandular complexes due to its varying prognostic outcomes.

Electrodeposited reduced graphene oxide-PEDOT:PSS/Nafion hybrid interface for the simultaneous determination of dopamine and serotonin.

The electrochemically deposited reduced graphene oxide-PEDOT:PSS/Nafion (rGO-PP/NF) hybrid material has provided a favorable interface for the simultaneous detection of dopamine (DA) and serotonin (5-HT). The rGO-PP/NF onto the Au seed layer of the flexible substrate was simple, and it was followed by the sequential electrophoretic deposition of GO, reduction at the optimal pH buffer media, electropolymerization of EDOT:PSS, and Nafion coating. The strong electron-transport capacity between rGO-PEDOT:PSS and the negatively charged Nafion matrix might allow the highly sensitive, simultaneous, and selective detection of DA and 5-HT due to its high affinity for cations. In the results of the electrochemical response, well-separated oxidation peaks were observed in a mixture that contained various concentrations of DA and 5-HT. It showed the dynamic sensing of DA and 5-HT in the ranges of 0.5-75 µM and 0.05-50 µM, respectively, and the detection limits of 0.17 and 0.16 µM, respectively. In the mixture of DA and 5-HT, the sensor had a detection limit of 0.1 µM for 5-HT and DA, and its sensitivities of DA and 5-HT were 99.3 and 86 µA/µMcm2. Furthermore, it demonstrated high selectivity, reproducibility, stability, and a recovery property in the human serum spike test that was good enough for the practical use.

Identification of Missense Variants Affecting Carcass Traits for Hanwoo Precision Breeding.

This study aimed to identify causal variants associated with important carcass traits such as weight and meat quality in Hanwoo cattle. We analyzed missense mutations extracted from imputed sequence data (ARS-UCD1.2) and performed an exon-specific association test on the carcass traits of 16,970 commercial Hanwoo. We found 33, 2, 1, and 3 significant SNPs associated with carcass weight (CW), backfat thickness (BFT), eye muscle area (EMA), and marbling score (MS), respectively. In CW and EMA, the most significant missense SNP was identified at 19,524,263 on BTA14 and involved the PRKDC. A missense SNP in the ZFAND2B, located at 107,160,304 on BTA2 was identified as being involved in BFT. For MS, missense SNP in the ACVR2B gene, located at 11,849,704 in BTA22 was identified as the most significant marker. The contribution of the most significant missense SNPs to genetic variance was confirmed to be 8.47%, 2.08%, 1.73%, and 1.19% in CW, BFT, EMA, and MS, respectively. We generated favorable and unfavorable haplotype combinations based on the significant SNPs for CW. Significant differences in GEBV (Genomic Estimated Breeding Values) were observed between groups with each favorable and unfavorable haplotype combination. In particular, the missense SNPs in PRKDC, MRPL9, and ANKFN1 appear to significantly affect the protein's function and structure, making them strong candidates as causal mutations. These missense SNPs have the potential to serve as valuable markers for improving carcass traits in Hanwoo commercial farms.

Real-time morphological detection of label-free submicron-sized plastics using flow-channeled differential interference contrast microscopy.

Owing to the surge in plastic waste generated during the COVID-19 pandemic, concerns regarding microplastic pollution in aqueous environments are increasing. Since microplastics (MPs) are broken down into submicron (< 1 µm) and nanoscale plastics, their real-time morphological detection in water is necessary. However, the decrease in the scattering cross-section of MPs in aqueous media precludes morphological detection by bright-field microscopy. To address this problem, we propose and demonstrate a differential interference contrast (DIC) system that incorporates a magnification-enhancing system to detect MPs in aqueous samples. To detect MPs in both the stationary and mobile phases, a microfluidic chip was designed, taking into consideration the imaging depth of focus and flow resistance. MPs of various sizes flowing in deionized, tap, and pond water at varying speeds were observed under Static and Flow conditions. Successful real-time morphological detection and quantification of polystyrene beads down to 200 nm at a constant flow rate in water were achieved. Thus, the proposed novel method can significantly reduce analysis time and improve the size-detection limit. The proposed DIC microscopy system can be coupled with Raman or infrared spectroscopy in future studies for chemical composition analysis. ENVIRONMENTAL IMPLICATION: Microplastics (MPs), particularly submicron plastics < 1-µm, can pose a risk to human health and aquatic ecosystems. Existing methods for detecting MPs in the aqueous phase have several limitations, including the use of expensive instruments and prolonged and labor-intensive procedures. Our results clearly demonstrated that a new low-cost flow-channeled differential interference contrast microscopy enables the real-time morphological detection and quantification of MPs down to 200 nm under flowing conditions without sample labeling. Consequently, our proposed rapid method for accurate quantitative measurements can serve as a valuable reference for detecting submicron plastics in water samples.

Immune microenvironment and lymph node yield in colorectal cancer.

BACKGROUND: Lymph node (LN) harvesting is associated with outcomes in colonic cancer. We sought to interrogate whether a distinctive immune milieu of the primary tumour is associated with LN yield. METHODS: A total of 926 treatment-naive patients with colorectal adenocarcinoma with more than 12 LNs (LN-high) were compared with patients with 12 or fewer LNs (LN-low). We performed immunohistochemistry and quantification on tissue microarrays for HLA class I/II proteins, beta-2-microglobulin (B2MG), CD8, CD163, LAG3, PD-L1, FoxP3, and BRAF V600E. RESULTS: The LN-high group was comprised of younger patients, longer resections, larger tumours, right-sided location, and tumours with deficient mismatch repair (dMMR). The tumour microenvironment showed higher CD8+ cells infiltration and B2MG expression on tumour cells in the LN-high group compared to the LN-low group. The estimated mean disease-specific survival was higher in the LN-high group than LN-low group. On multivariate analysis for prognosis, LN yield, CD8+ cells, extramural venous invasion, perineural invasion, and AJCC stage were independent prognostic factors. CONCLUSION: Our findings corroborate that higher LN yield is associated with a survival benefit. LN yield is associated with an immune high microenvironment, suggesting that tumour immune milieu influences the LN yield.

Clinical, pathological, genetics and intratumoural immune milieu of micropapillary carcinoma of the colon.

AIM: Micropapillary carcinoma (MPC) is a recognised WHO variant of colonic carcinoma (CC), although little is known about its prognosis, immune microenvironment and molecular alterations. We investigated its clinical, pathological and immunological characteristics. METHODS: We assessed 903 consecutive CCs and used the WHO definition to identify MPC. We recorded serrated and mucinous differentiation and mismatch repair (MMR) status. We performed immunohistochemistry and quantification on tissue microarrays for HLA class I/II proteins, beta-2-microglobulin (B2MG), CD8, CD163, LAG3, PD-L1, FoxP3, PD-L1and BRAF V600E. RESULTS: We classified 8.6% (N=78) of CC as MPC. Relative to non-MPC, MPC was more often high grade (p=0.03) and showed serrated morphology (p<0.01); however, we found no association with extramural venous invasion (p=0.41) and American Joint Committee on Cancer stage (p=0.95). MPCs showed lower numbers of CD8 positive lymphocytes (p<0.01), lower tumour cell B2MG expression (p=0.04) and lower tumour cell PD-L1 expression (p<0.01). There was no difference in HLA class I/II, LAG3, FOXP3, CD163 and PD-L1 positive histiocytes. There was no association with MMR status or BRAF V600E relative to non-MPC. MPC was not associated with decreased disease-specific survival (p=0.36). CONCLUSION: MPCs are associated with high-grade differentiation and a less active immune microenvironment than non-MPC. MPC is not associated with inferior disease-specific survival.

Comparisons of treatment satisfaction and health-related quality of life in patients with rheumatoid arthritis treated with tofacitinib and adalimumab.

BACKGROUND: As significant advances in the field of treatment for rheumatoid arthritis (RA), there is a great need to identify the healthcare outcomes such as treatment satisfaction and health-related quality of life (HRQoL) of patients with various treatment options. This study aims to identify the difference in the treatment satisfaction and HRQoL of patients with RA using different treatment options, by comparing the treatment satisfaction and HRQoL in patients with RA treated with tofacitinib and adalimumab in real-world settings in Korea, using propensity score methods. METHODS: In this non-interventional, multicenter, cross-sectional study (NCT03703817), a total of 410 patients with RA diagnosis were recruited in 21 university-based hospitals throughout Korea. The treatment satisfaction and HRQoL were assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM) and EQ-5D questionnaires self-reported by the patients. This study compared outcomes between two drug groups in unweighted, greedy matching, and stabilized inverse probability of treatment weight (IPTW) samples using propensity score. RESULTS: In all three samples, tofacitinib group showed higher convenience domain of TSQM than that in the adalimumab group, but not effectiveness, side effects, and global satisfaction domains. Multivariable analysis using the covariates of demographic and clinical characteristics of the participants also showed consistent results in TSQM. No statistical difference in EQ-5D-based HRQoL was identified between two drug groups in all three samples. CONCLUSIONS: This study identified that tofacitinib shows higher treatment satisfaction in the convenience domain of TSQM rather than adalimumab, suggesting that various factors such as drug formulation, route or frequency of administration, and storage can have an impact on the treatment satisfaction, especially the convenience domain. These findings may be useful to patients and physicians when determining treatment options. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03703817.

Dynamics of disease progression during treatment with Osimertinib in patients with EGFR T790M-positive non-small cell lung cancer.

BACKGROUND: Patterns of treatment failure and subsequent treatment in non-small cell lung cancer (NSCLC) patients treated with osimertinib are scarcely known. We analyzed the disease progression during osimertinib treatment to identify potential treatment strategies. METHODS: We identified advanced NSCLC patients who commenced osimertinib treatment after progression on previous epidermal growth factor receptor (EGFR)-tyrosine-kinase inhibitor (TKI) from June 2014 to November 2018 from electronic records. Patients' tumor characteristics, efficacy outcomes, affected organs from radiology studies, and treatment modalities before and after osimertinib were analyzed. RESULTS: Eighty-four patients were included. At osimertinib initiation, bone (50.0%) and brain (41.9%) were the commonest single metastatic sites, whereas thoracic involvement (73.3%) was more frequent than bone (27.4%) or brain (20.2%) metastasis during disease progression on osimertinib. Oligo-progressive disease (PD) and central nervous system (CNS)-sanctuary PD were observed in 15 (17.9%) and 3 (3.6%) patients, respectively. Most patients without brain metastasis (BM) at osimertinib initiation remained BM-free (46/49, 93.9%), and 60% of patients (21/35) with pre-existing BM showed intracranial disease control despite extracranial PD. The resistance mechanisms to osimertinib were explored in 23 patients (27.4%), and T790M-loss was observed in 14 patients (60.9%) who had worse survival outcomes than those without T790M-loss (progression-free survival, 5.4 vs. 16.5 months, p = 0.02; overall survival, not reached, p = 0.03). CONCLUSION: PD during osimertinib treatment occurred preferentially in the thorax and pre-existing sites. Extracranial PD prevailed over intracranial PD regardless of baseline BM and prior brain radiation. These results support osimertinib's intracranial efficacy and may guide treatment strategies for EGFR-mutated NSCLC with BM.

Label-free detection and discrimination of respiratory pathogens based on electrochemical synthesis of biomaterials-mediated plasmonic composites and machine learning analysis.

Seasonal outbreaks of respiratory viral infections remain a global concern, with increasing morbidity and mortality rates recorded annually. Timely and false responses contribute to the widespread of respiratory pathogenic diseases owing to similar symptoms at an early stage and subclinical infection. The prevention of emerging novel viruses and variants is also a big challenge. Reliable point-of-care diagnostic assays for early infection diagnosis play a critical role in the response to threats of epidemics or pandemics. We developed a facile method for specifically identifying different viruses based on surface-enhanced Raman spectroscopy (SERS) with pathogen-mediated composite materials on Au nanodimple electrodes and machine learning (ML) analyses. Virus particles were trapped in three-dimensional plasmonic concave spaces of the electrode via electrokinetic preconcentration, and Au films were simultaneously electrodeposited, leading to the acquisition of intense and in-situ SERS signals from the Au-virus composites for ultrasensitive SERS detection. The method was useful for rapid detection analysis (<15 min), and the ML analysis for specific identification of eight virus species, including human influenza A viruses (i.e., H1N1 and H3N2 strains), human rhinovirus, and human coronavirus, was conducted. The highly accurate classification was achieved using the principal component analysis-support vector machine (98.9%) and convolutional neural network (93.5%) models. This ML-associated SERS technique demonstrated high feasibility for direct multiplex detection of different virus species for on-site applications.

Digital Breast Tomosynthesis Plus Ultrasound Versus Digital Mammography Plus Ultrasound for Screening Breast Cancer in Women With Dense Breasts.

OBJECTIVE: To compare the outcomes of digital breast tomosynthesis (DBT) screening combined with ultrasound (US) with those of digital mammography (DM) combined with US in women with dense breasts. MATERIALS AND METHODS: A retrospective database search identified consecutive asymptomatic women with dense breasts who underwent breast cancer screening with DBT or DM and whole-breast US simultaneously between June 2016 and July 2019. Women who underwent DBT + US (DBT cohort) and DM + US (DM cohort) were matched using 1:2 ratio according to mammographic density, age, menopausal status, hormone replacement therapy, and a family history of breast cancer. The cancer detection rate (CDR) per 1000 screening examinations, abnormal interpretation rate (AIR), sensitivity, and specificity were compared. RESULTS: A total of 863 women in the DBT cohort were matched with 1726 women in the DM cohort (median age, 53 years; interquartile range, 40-78 years) and 26 breast cancers (9 in the DBT cohort and 17 in the DM cohort) were identified. The DBT and DM cohorts showed comparable CDR (10.4 [9 of 863; 95% confidence interval {CI}: 4.8-19.7] vs. 9.8 [17 of 1726; 95% CI: 5.7-15.7] per 1000 examinations, respectively; P = 0.889). DBT cohort showed a higher AIR than the DM cohort (31.6% [273 of 863; 95% CI: 28.5%-34.9%] vs. 22.4% [387 of 1726; 95% CI: 20.5%-24.5%]; P < 0.001). The sensitivity for both cohorts was 100%. In women with negative findings on DBT or DM, supplemental US yielded similar CDRs in both DBT and DM cohorts (4.0 vs. 3.3 per 1000 examinations, respectively; P = 0.803) and higher AIR in the DBT cohort (24.8% [188 of 758; 95% CI: 21.8%-28.0%] vs. 16.9% [257 of 1516; 95% CI: 15.1%-18.9%; P < 0.001). CONCLUSION: DBT screening combined with US showed comparable CDR but lower specificity than DM screening combined with US in women with dense breasts.

A Randomized Phase II Study of Irinotecan Plus Cisplatin with or without Simvastatin in Ever-Smokers with Extended Disease Small Cell Lung Cancer.

PURPOSE: This study evaluated whether an addition of simvastatin to chemotherapy improves survival in ever-smokers with extensive disease (ED)-small cell lung cancer (SCLC). Materials and Methods: This is an open-label randomized phase II study conducted in National Cancer Center (Goyang, Korea). Chemonaive patients with ED-SCLC, smoking history (≥ 100 cigarettes lifetime), and Eastern Cooperative Oncology Group performance status of ≤ 2 were eligible. Patients were randomized to receive irinotecan plus cisplatin alone or with simvastatin (40 mg once daily orally) for a maximum of six cycles. Primary endpoint was the the 1-year survival rate. RESULTS: Between September 16, 2011, and September 9, 2021, 125 patients were randomly assigned to the simvastatin (n=62) or control (n=63) groups. The median smoking pack year was 40 years. There was no significant difference in the 1-year survival rate between the simvastatin and control groups (53.2% vs. 58.7%, p=0.535). The median progression-free survival and overall survival between the simvastatin arm vs. the control groups were 6.3 months vs. 6.4 months (p=0.686), and 14.4 months vs. 15.2 months, respectively (p=0.749). The incidence of grade 3-4 adverse events was 62.9% in the simvastatin group and 61.9% in the control group. In the exploratory analysis of lipid profiles, patients with hypertriglyceridemia had significantly higher 1-year survival rates than those with normal triglyceride levels (80.0% vs. 52.7%, p=0.046). CONCLUSION: Addition of simvastatin to chemotherapy provided no survival benefit in ever-smokers with ED-SCLC. Hypertriglyceridemia may be associated with better prognosis in these patient population.

COVID-19 vaccine refusal associated with health literacy: findings from a population-based survey in Korea.

BACKGROUND: Poor health literacy is associated with lower utilization of preventable services. However, the relationship between health literacy and COVID-19 vaccine hesitancy remains controvertible. METHODS: This study used data from 229,242 individuals who completed the Community Health Survey in Korea from August 16 to October 31 in 2021. To operationalize COVID-19 vaccine hesitancy, we measured vaccine refusal, which is defined as not having been vaccinated and not intending to get vaccinated against COVID-19. Health literacy is operationalized in two dimensions; the ability to understand spoken directions from health professionals and the ability to understand written information regarding health. Covariates include sex, age, educational level, marital status, employment status, basic living security pension status, and subjective health status. Two multivariable logistic regression models were run to determine factors associated with COVID-19 vaccine refusal. Model 1 included sociodemographic characteristics and subjective health status. Model 2 added two health literacy variables. Odds ratio (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Only 3.9% of the Korean adult population were estimated to refuse COVID-19 vaccine. The most commonly cited reasons for COVID-19 vaccine refusal were concerns about vaccine adverse events (47.6%), followed by the assessment of one's own health status (29.5%). Individuals who found spoken directions very difficult to understand were more likely to refuse COVID-19 vaccine than those who found spoken directions very easy (OR = 1.55, 95% CI: 1.28-1.87, p < 0.001). People who did not pay attention to written information were more likely to refuse COVID-19 vaccine than those who reported it to be very easy to understand (OR = 1.28, 95% CI: 1.13-1.45, p < 0.001). People in all other categories of the literacy spectrum for either spoken or written information did not have an increased risk of COVID-19 vaccine refusal. CONCLUSION: Health literacy was significantly associated with COVID-19 vaccine refusal. Health literacy programs could be beneficial to reduce vaccine refusal, particularly for the people who find spoken directions from health professionals very difficult to understand and those who do not pay attention to written information.

Mechanobiological Adaptation to Hyperosmolarity Enhances Barrier Function in Human Vascular Microphysiological System.

In infectious disease such as sepsis and COVID-19, blood vessel leakage treatment is critical to prevent fatal progression into multi-organ failure and ultimately death, but the existing effective therapeutic modalities that improve vascular barrier function are limited. Here, this study reports that osmolarity modulation can significantly improve vascular barrier function, even in an inflammatory condition. 3D human vascular microphysiological systems and automated permeability quantification processes for high-throughput analysis of vascular barrier function are utilized. Vascular barrier function is enhanced by >7-folds with 24-48 h hyperosmotic exposure (time window of emergency care; >500 mOsm L-1 ) but is disrupted after hypo-osmotic exposure (<200 mOsm L-1 ). By integrating genetic and protein level analysis, it is shown that hyperosmolarity upregulates vascular endothelial-cadherin, cortical F-actin, and cell-cell junction tension, indicating that hyperosmotic adaptation mechanically stabilizes the vascular barrier. Importantly, improved vascular barrier function following hyperosmotic exposure is maintained even after chronic exposure to proinflammatory cytokines and iso-osmotic recovery via Yes-associated protein signaling pathways. This study suggests that osmolarity modulation may be a unique therapeutic strategy to proactively prevent infectious disease progression into severe stages via vascular barrier function protection.

Vibroacoustic Characteristics of a Specific Patterned Polymer with Graphene for an Electrostatic Speaker.

Graphene/polymer actuators were developed using bilayer graphene and various polymer substrates for use as transparent, flexible, and robust electrostatic speaker units. Additionally, a resonant frequency shift was induced using a polymer substrate on which various micropatterns were transferred to boost bass. The total sound pressure level (SPL) in the graphene/polymer actuator was measured by a sweep, and the frequency of the spectrum was confirmed to be one-third that of the octave band frequency. The change in the vibroacoustic characteristic with changes in Young's modulus and density was studied for the polymers of the same size and thickness. Particularly, the possibility of boosting bass was confirmed by inducing a resonant frequency shift and increasing the total SPL by adding micropatterns on a polymer substrate under the same conditions. The resonance frequency of 523 Hz and the SPL of 54 dBA in flat polymer film became 296 Hz and 69 dBA in a specific pattern, which produced a sound of >15 dB based on the same flat polymer. We expect that the design and information provided herein can provide the key parameters required to change the resonant frequency in small-size devices for the application of graphene/polymer thin-film actuators.