The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has provided insights for updating current coronavirus disease 2019 (COVID-19) vaccines. We examined ...the neutralizing activity of Abs induced by a BA.4/5-containing bivalent mRNA vaccine against Omicron subvariants BN.1 and XBB.1.5. We recruited 40 individuals who had received a monovalent COVID-19 booster dose after a primary series of COVID-19 vaccinations and will be vaccinated with a BA.4/5-containing bivalent vaccine. Sera were collected before vaccination, one month after, and three months after a bivalent booster. Neutralizing Ab (nAb) titers were measured against ancestral SARS-CoV-2 and Omicron subvariants BA.5, BN.1, and XBB.1.5. BA.4/5-containing bivalent vaccination significantly boosted nAb levels against both ancestral SARS-CoV-2 and Omicron subvariants. Participants with a history of SARS-CoV-2 infection had higher nAb titers against all examined strains than the infection-naïve group. NAb titers against BN.1 and XBB.1.5 were lower than those against the ancestral SARS-CoV-2 and BA.5 strains. These results suggest that COVID-19 vaccinations specifically targeting emerging Omicron subvariants, such as XBB.1.5, may be required to ensure better protection against SARS-CoV-2 infection, especially in high-risk groups.
This study examined the effects of the incorporation of carbon fiber (CF) and silicon carbide powder (SCP) into a high temperature vulcanized (HTV) silicone rubber, poly(dimethylsiloxane) (PDMS) ...containing vinyl groups on the ablation properties using an oxy-acetylene torch test. The ablation test results showed that CF enhanced the hardness of the char formed on the composite surface during the oxy-acetylene torch test and was an important factor determining the ablation properties. SCP was also beneficial in enhancing the surface char hardness of the HTV/CF composite. A new method was devised to evaluate the ablation properties more objectively by measuring the time elapsed for a rectangular-shaped silicone rubber composite with specimens loaded with a constant weight to burn and fail off during the oxy-acetylene torch test. The mechanical properties of the silicone rubber composites were also examined as a function of the additive content using a universal test machine (UTM).
To investigate the correlation between dyspeptic symptoms and gastric motility parameters measured by magnetic resonance imaging (MRI) using volumetry and motility indices in patients with ...Parkinson's disease (PD).
In this IRB-approved study, MRI datasets obtained from August 2014 to May 2016 in 38 PD patients were retrospectively analyzed. Patients underwent a 120-minute-long MRI study using a liquid test meal and 8 sets of scans. Gastric content volume (GCV) and total volume (TGV), gastric half emptying time (T1/2), motility index (GMI), accommodation (GA), and emptying (GE) values were acquired. These measurements were compared between patients according to the presence of gastric symptoms: early satiety (n = 25), epigastric pain (n = 13), and dyspepsia (n = 28).
Patients with early satiety showed significantly decreased GE of GCV and TGV (p < 0.001 and p = 0.017). Dyspeptic patients had significantly decreased GE of GCV and GMI (p = 0.001 and p = 0.029). GE of GCV at 90 and 120 minutes were significantly lower in patients with early satiety (p = 0.001 and p = 0.002). GE of GCV and GMI at 90 minutes were significantly decreased in patients with dyspepsia (p = 0.004 and p = 0.002). T1/2 of GCV was prolonged in patients with early satiety, epigastric pain, and dyspepsia (p = 0.004, p = 0.041, and p = 0.023). T1/2 of TGV also delayed in patients with early satiety (p = 0.023). GMI at 90 minutes was significantly correlated with dyspepsia on multivariable analysis (p = 0.028).
Gastric motility can be quantitatively assessed by MRI, showing decreased GMI, delayed GE, and prolonged T1/2 in PD patients with early satiety or dyspepsia.
Purpose
Salvage treatment including surgery and radiotherapy (RT) for recurrent or progressive meningioma is not an easy task, especially for the skull base location. And yet, criteria for adjuvant ...radiotherapy after initial surgery are not clearly defined for WHO grade I/II meningioma. We determined prognostic factors for recurrence and evaluated the benefit of risk group-adapted adjuvant RT for WHO grade I/II meningioma in the skull base.
Methods
We reviewed 272 patients who underwent surgery and were pathologically confirmed with WHO grade I or II skull base meningioma between January 2000 and July 2017. Subgroup analyses were performed for WHO grade I (259 patients) and WHO grade II (13 patients) meningiomas to evaluate the benefit of RT in each subgroup.
Results
Patients with WHO grade II meningiomas tended to present more neurologic symptoms and to receive RT more frequently. In prognostic factor analysis, tumor size (
p
= 0.039), surgical extent (
p
< 0.001), and RT (
p
= 0.005) were associated with recurrence-free survival (RFS). In subgroup analysis of WHO grade I, RFS was significantly better in RT group after matching other variables. The risk stratification was performed using three risk factors (petroclival location, tumor size, Simpson grade) in WHO grade I patients, and significantly different RFS was observed according to the risk group in non-RT patients.
Conclusions
Tumor size, Simpson grade, and adjuvant RT were prognostic factors. The risk group-adapted approach can facilitate the selection of patients who may benefit from adjuvant RT for WHO grade I/II skull base meningiomas.
Genome-wide association studies of gastric cancer (GC) cases have revealed common gastric cancer susceptibility loci with low effect size. We investigated rare variants with high effect size via ...whole-exome sequencing (WES) of subjects with familial clustering of gastric cancer. WES of DNAs from the blood of 19 gastric cancer patients and 36 unaffected family members from 14 families with two or more gastric cancer patients were tested. Linkage analysis combined with association tests were performed using Pedigree Variant Annotation, Analysis, and Search Tool (pVAAST) software. Based on the logarithm of odds (LOD) and permutation-based composite likelihood ratio test (CLRT) from pVAAST, MUC4 was identified as a predisposing gene (LOD P-value = 1.9×10−5; permutation-based P-value of CLRT ≤ 9.9×10−9). In a larger cohort consisting of 597 GC patients and 9,759 healthy controls genotyped with SNP array, we discovered common variants in MUC4 regions (rs148735556, rs11717039, and rs547775645) significantly associated with GC supporting the association of MUC4 with gastric cancer. And the MUC4 variants were found in higher frequency in The Cancer Genome Atlas Study (TCGA) germline samples of patients with multiple cancer types. Immunohistochemistry indicated that MUC4 was downregulated in the noncancerous gastric mucosa of subjects with MUC4 germline missense variants, suggesting that loss of the protective function of MUC4 predisposes an individual to gastric cancer. Rare variants in MUC4 can be novel gastric cancer susceptibility loci in Koreans possessing the familial clustering of gastric cancer.
Background
The purpose of this nationwide age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in ankylosing spondylitis (AS).
Methods
The data ...in this study, spanning from January 1, 2010 to December 31, 2014, was obtained from a database maintained by the Korean National Health Insurance Service. A total of 12,988 patients with a diagnosis of AS were enrolled. The control group consisted of 64,940 age-sex-stratified matching subjects without AS. The 6year ischemic stroke incidence rate for each group was calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke.
Results
During the follow-up period, 73 patients (0.56%) in the AS group and 250 patients (0.38%) in the control group developed ischemic stroke (
p
= 0.0041). The hazard ratio of ischemic stroke in the AS group was 1.46 (95% confidence interval 95% CI, 1.13–1.90) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the AS group was 1.35 (95% CI, 1.04–1.75) after controlling for demographics and comorbid medical disorders. According to subgroup analysis, in female and diabetes and non-hypertension and dyslipidemia subgroups, ischemic stroke incidence rates were significantly higher in AS patients than those in control group.
Conclusion
Our nationwide longitudinal study suggests an increased risk of ischemic stroke in AS patients.
This study aimed to explore the prognostic impact of spatial distribution of tumor‐infiltrating lymphocytes (TILs) quantified by deep learning (DL) approaches based on digitalized whole‐slide images ...stained with hematoxylin and eosin in patients with colorectal cancer (CRC). The prognostic impact of spatial distributions of TILs in patients with CRC was explored in the Yonsei cohort (n = 180) and validated in The Cancer Genome Atlas (TCGA) cohort (n = 268). Two experienced pathologists manually measured TILs at the most invasive margin (IM) as 0–3 by the Klintrup–Mäkinen (KM) grading method and this was compared to DL approaches. Inter‐rater agreement for TILs was measured using Cohen's kappa coefficient. On multivariate analysis of spatial TIL features derived by DL approaches and clinicopathological variables including tumor stage, microsatellite instability, and KRAS mutation, TIL densities within 200 μm of the IM (f_im200) remained the most significant prognostic factor for progression‐free survival (PFS) (hazard ratio HR 0.004 95% confidence interval, CI, 0.0001–0.15, p = 0.0028) in the Yonsei cohort. On multivariate analysis using the TCGA dataset, f_im200 retained prognostic significance for PFS (HR 0.031 95% CI 0.001–0.645, p = 0.024). Inter‐rater agreement of manual KM grading was insignificant in the Yonsei (κ = 0.109) and the TCGA (κ = 0.121) cohorts. The survival analysis based on KM grading showed statistically significant different PFS in the TCGA cohort, but not the Yonsei cohort. Automatic quantification of TILs at the IM based on DL approaches shows prognostic utility to predict PFS, and could provide robust and reproducible TIL density measurement in patients with CRC.
In order to evaluate the effect of daily consumption of fruit and vegetable juice on the human intestinal microbial community, we compared changes in the gut microbiota and extracellular vesicles in ...human feces and bowel, and skin symptoms at the baseline and 3 weeks post juice consumption of 22 participants. After 3 weeks of juice consumption, a significant increase in the richness of microbiota (α-diversity,
P
< 0.05) was observed. It was accompanied by an abundance in Faecalibacterium (bacterial: from 1.62 ± 0.80% to 2.14 ± 0.72% and extra vesicle: 2.49 ± 1.49% to 6.06 ± 3.07%;
P
< 0.05 in all cases). At the end of the study period, there were reductions in body weight regardless of sex (
P
< 0.05) and improvements of the symptoms including diarrhea, constipation, fatigue, and skin problems. Eating fruits and vegetables could help modulate the profile of the fecal microbiota and alleviate bowel and skin troubles, and fatigue.
Background
This study evaluated whether an addition of bevacizumab to erlotinib improves clinical outcomes in patients with advanced EGFR‐mutated non–small cell lung cancer (NSCLC).
Methods
This is ...an open‐label, multicenter, randomized Phase 2 study in South Korea. Chemonaïve patients with Stage IIIB/IV NSCLC with EGFR 19 deletion or L858R mutation were eligible. Asymptomatic brain metastasis (BM) was enrolled without local treatment. Patients received either erlotinib plus bevacizumab or erlotinib.
Results
Between December 2016 and March 2019, 127 patients were randomly assigned to receive erlotinib plus bevacizumab (n = 64) or erlotinib (n = 63). Fifty‐nine (46.5%) patients had baseline BM. Fewer patients in the erlotinib plus bevacizumab arm received radiotherapy for BM than in the erlotinib arm (10.3% vs. 40.0%). A trend toward longer progression‐free survival (PFS) was observed in the erlotinib plus bevacizumab arm compared with the erlotinib alone arm; however, it was not statistically significant (median PFS, 17.5 months vs. 12.4 months; hazard ratio HR, 0.74; 95% CI, 0.51–1.08; p = .119). The unplanned subgroup analysis showed a longer PFS with erlotinib plus bevacizumab in patients with BM (median PFS, 18.6 months vs. 10.3 months; HR, 0.54; 95% CI, 0.31–0.95; p = .032). Grade 3 or worse adverse events occurred in 56.6% of the erlotinib plus bevacizumab arm and 20.6% of the erlotinib arm.
Conclusions
Although it was not statistically significant, a trend to improvement in PFS was observed in patients with erlotinib plus bevacizumab compared to erlotinib alone.
Plain Language Summary
A randomized Phase 2 study compared erlotinib with or without bevacizumab in previously untreated patients with advanced non–small cell lung cancer with EGFR mutation. The erlotinib plus bevacizumab failed to improve median progression‐free survival compared with the erlotinib alone. However, the progression‐free survival benefit from erlotinib plus bevacizumab was found in patients with brain metastasis with no severe hemorrhagic adverse effects.
A trend to improvement in progression‐free survival was observed in patients with advanced EGFR‐mutated non–small cell lung cancer treated with erlotinib plus bevacizumab compared with erlotinib alone. The progression‐free survival benefit from erlotinib plus bevacizumab was most significant in patients with brain metastasis with no severe hemorrhagic adverse effects.
BACKGROUNDOccupational injuries and diseases are life events that significantly impact an individuals' identity. In this study, we examined the trajectories of self-esteem among victims of ...occupational injury and disease and their relation to health. METHODSThe Panel Study of Workers' Compensation Insurance conducted annual follow-ups on workers who had experienced occupational injury or disease. A total of 2,000 participants, who had completed medical care, were followed from 2013 to 2017. Growth mixture modeling was utilized to identify latent classes in the self-esteem trajectory. Additionally, logistic regressions were conducted to explore the association between trajectory membership, baseline predictors, and outcomes. RESULTSThree distinct trajectory classes were identified. Total 65.8% of the samples (n = 1,316) followed an increasing self-esteem trajectory, while 31.1% (n = 623) exhibited a constant trajectory, and 3.1% (n = 61) showed a decreasing trajectory. Individuals with an increasing trajectory were more likely to have a higher educational attainment (odds ratio OR, 1.86; 95% confidence interval CI, 1.20-2.88), an absence of a moderate-to-severe disability rating (OR, 0.49; 95% CI, 0.25-0.96), no difficulty in daily living activities (OR, 0.81; 95% CI, 0.75-0.88), and were economically active (re-employed: OR, 2.46; 95% CI, 1.52-3.98; returned to original work: OR, 4.46; 9% CI, 2.65-7.50). Those with a decreasing self-esteem trajectory exhibited an increased risk of poor subjective health (OR, 1.89; 95% CI, 0.85-4.85 in 2013 to OR, 3.17; 95% CI, 1.04-13.81 in 2017), whereas individuals with an increasing trajectory showed a decreased risk (OR, 0.54; 95% CI, 0.43-0.68 in 2013 to OR, 0.44; 95% CI, 0.33-0.57 in 2017). CONCLUSIONOur findings emphasize the diversity of psychological responses to occupational injury or disease. Policymakers should implement interventions to enhance the self-esteem of victims.
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