Abstract Objectives To develop and validate a new risk-of-bias tool for nonrandomized studies (NRSs). Study Design and Setting We developed the Risk of Bias Assessment Tool for Nonrandomized Studies ...(RoBANS). A validation process with 39 NRSs examined the reliability (interrater agreement), validity (the degree of correlation between the overall assessments of RoBANS and Methodological Index for Nonrandomized Studies MINORS, obtained by plotting the overall risk of bias relative to effect size and funding source), face validity with eight experts, and completion time for the RoBANS approach. Results RoBANS contains six domains: the selection of participants, confounding variables, the measurement of exposure, the blinding of the outcome assessments, incomplete outcome data, and selective outcome reporting. The interrater agreement of the RoBANS tool except the measurement of exposure and selective outcome reporting domains ranged from fair to substantial. There was a moderate correlation between the overall risks of bias determined using RoBANS and MINORS. The observed differences in effect sizes and funding sources among the assessed studies were not correlated with the overall risk of bias in these studies. The mean time required to complete RoBANS was approximately 10 min. The external experts who were interviewed evaluated RoBANS as a “fair” assessment tool. Conclusions RoBANS shows moderate reliability, promising feasibility, and validity. The further refinement of this tool and larger validation studies are required.
To develop a practical thyroid imaging reporting and data system (TIRADS) with which to categorize thyroid nodules and stratify their malignant risk.
The institutional review board approved this ...retrospective study, and the requirement to obtain informed consent for the review of images and records was waived. From May to December 2008, ultrasonographically (US)-guided fine-needle aspiration biopsy (FNAB) was performed in 3674 focal thyroid nodules in 3414 consecutive patients. The study included the 1658 thyroid nodules (≥1 cm in maximum diameter at US) in 1638 patients (1373 women, 265 men) for which pathologic diagnosis or follow-up findings were available. Univariate and multivariate analyses with generalized estimating equations were performed to investigate the relationship between suspicious US features and thyroid cancer. A score for each significant factor was assigned and multiplied by the β coefficient obtained for each significant factor from multivariate logistic regression analysis. Scores for each significant factor were then added, resulting in an equation that fitted the probability of malignancy in thyroid nodules. The authors evaluated the fitted probability by using a regression equation; the risk of malignancy was determined according to the number of suspicious US features.
The following US features showed a significant association with malignancy: solid component, hypoechogenicity, marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape. As the number of suspicious US features increased, the fitted probability and risk of malignancy also increased. Positive predictive values according to the number of suspicious US features were significantly different (P < .001).
Risk stratification of thyroid malignancy by using the number of suspicious US features allows for a practical and convenient TIRADS.
This study aimed to investigate the efficacy of different COVID-19 booster vaccines by measuring the serum antibody titer. SARS-CoV-2 anti-nucleocapsid protein antibody (N-Ab), anti-spike protein ...antibody (S-Ab), and neutralizing antibody (Neut.Ab) were measured before and 4–6 weeks after booster vaccinations in healthcare personnel with a previous vaccination within 3–6 months. Personnel who previously received two doses of ChAdOx1 vaccine or two doses of BNT162b2 vaccine received the BNT162b2 vaccine (AAP and PPP groups, respectively). Personnel who previously received two doses of mRNA-1273 received the same vaccine as a booster dose (MMM group). Of the 917 participants, the AAP, MMM, and PPP groups comprised 837 (91.3%), 27 (2.9%), and 53 (5.8%) participants, respectively. The pre-booster S-Ab and Neut.Ab titer were significantly lower in the AAP group. After the booster vaccination, all participants were positive for S-Ab and Neut.Ab; furthermore, the S-Ab and Neut.Ab titer significantly increased in all three groups, although the post-booster S-Ab was lower in the AAP group than in the other groups. The post-booster Neut.Ab titer showed no significant difference among the groups. Our study’s results suggest that booster vaccination, after two prior vaccinations, shows a significant effect regardless of the type of vaccine administered.
A biopsy of first recurrence or metastatic disease is recommended to re-evaluate oestrogen receptor status in patients with breast cancer and to select appropriate treatment. However, retesting for ...oestrogen receptor status with rebiopsy is not always feasible, depending on lesion location and the risk associated with biopsy, and in these cases clinicians continue to treat patients according to the oestrogen receptor status of the primary tumour. Consequently suboptimal therapy might be offered to these patients. We assessed the diagnostic accuracy and safety of 16α-18Ffluoro-17β-oestradiol (18F-FES) PET-CT to assess oestrogen receptor status in patients with recurrent or metastatic breast cancer.
We did a prospective cohort study at the Asan Medical Center, Seoul, South Korea. Eligible patients had breast cancer, with first recurrence or metastatic disease at presentation, were 19 years or older, and had an Eastern Cooperative Oncology Group performance status of 0–2. The primary objective was to show the agreement between qualitative 18F-FES PET-CT interpretation and the results of oestrogen receptor expression by immunohistochemical assay, a non-reference standard test. Whole-body 18F-FES PET-CT imaging was done after intravenous injection of 111–222 MBq of 18F-FES, with dosing primarily determined by radiation dosimetry analysis. 18F-FES uptake above background intensity was interpreted as positive. Efficacy was assessed in all patients with histologically confirmed recurrent or metastatic breast cancer who received 18F-FES and had PET-CT images available (intention-to-diagnose analysis), and safety was assessed in all patients who received 18F-FES. This study is registered with ClinicalTrials.gov, number NCT01986569.
Between Nov 27, 2013, and Nov 10, 2016, 93 patients were enrolled. Of the 85 patients included in the efficacy analysis, 47 (55%) were oestrogen receptor-positive and 38 (45%) were oestrogen receptor-negative. Positive status percent agreement between the 18F-FES PET-CT results and oestrogen receptor status by immunohistochemical assay was 76·6% (95% CI 62·0–87·7) and the negative status percent agreement was 100·0% (90·8–100·0). Patients who were oestrogen receptor-positive and had a positive 18F-FES PET-CT result had a significantly higher progesterone receptor expression than those who were oestrogen receptor-positive and had a negative 18F-FES PET-CT result (23 68% of 34 patients vs 0 of 11 patients; p<0·0001). The most common adverse event was procedural pain in nine (10%) of 90 patients injected with 18F-FES. No adverse events were related to the study drug except injection site pain in one (1%) patient. No serious adverse events were recorded.
The high negative percent agreement between 18F-FES PET-CT and oestrogen receptor status by immunohistochemical assay in this cohort suggests that positive 18F-FES uptake by recurrent or metastatic oestrogen receptor-positive breast cancer lesions could be an alternative to oestrogen receptor assays in this setting. Staging assessment should include 18F-FES PET-CT when retesting oestrogen receptor status is not feasible.
Asan Institute for Life Sciences, Ministry of Health and Welfare, South Korea.
We aimed to identify the presence of the measles IgG antibody (mIgG-Ab) in healthcare personnel and finding out who needs the measles vaccination. The history of measles vaccination was obtained from ...the national vaccine registry. A baseline mIgG-Ab test was performed, and the measles vaccine was administered to participants who tested negative or equivocal for mIgG-Abs. During the study, 2885 (87.3%) of the 3303 employees were tested for measles serostatus. The baseline seropositivity rate for mIgG-Abs was 91.9%. Among the 234 seronegative cases, 82.9% were born after 1985. The seroprevalence rate was lower in those who received the measles–mumps–rubella (MMR) vaccine >10 years before the testing time, especially if they were born after 1985 and if there was only one previous record of vaccination. Among the 234 seronegative cases, MMR vaccination was administered in 174 cases, of which serostatus was evaluated in 146 cases. After the first dose, positive seroconversion was achieved in 126 participants (86.3%). After a second dose, 15 achieved (75.0%) positive seroconversion. In healthcare personnel born after the period when measles incidence significantly decreased, it may be necessary to reassess their immune status for measles if more than 10 years have elapsed since the last vaccination.
Tumor vessels are leaky and immature, which causes poor oxygen and nutrient supply to tumor vessels and results in cancer cell metastasis to distant organs. This instability of tumor blood vessels ...also makes it difficult for anticancer drugs to penetrate and reach tumors. Numerous tumor vessel normalization approaches have been investigated for improving drug delivery into tumors. In this study, we investigated whether phosphoinositide 3-kinase (PI3K) inhibitors are able to improve vascular structure and function over the prolonged period necessary to achieve effective vessel normalization. The PI3K inhibitors, HS-173 and BEZ235 potently suppressed tumor growth and hypoxia, and increased tumor apoptosis in animal models. PI3K inhibitors also induced a regular, flat monolayer of endothelial cells (ECs) in vessels, improving stability of vessel structure, and normalized tumor vessels by increasing vascular maturity, pericyte coverage, basement membrane thickness, and tight-junctions. These effects resulted in a decrease in tumor vessel tortuosity and vessel thinning, and improved vessel function and blood flow. The tumor vessel stabilization effect of the PI3K inhibitor HS-173 also decreased the number of metastatic lung nodules in vivo metastasis model. Furthermore, HS-173 improved the delivery of doxorubicin into the tumor region, enhancing its anticancer effects. Mechanistic studies suggested that PI3K inhibitor HS-173-induced vessel normalization reflected changes in endothelial Notch signaling. Taken together, our findings indicate that vessel normalization by PI3K inhibitors restrained tumor growth and metastasis while improving chemotherapy by enhancing drug delivery into the tumor, suggesting that HS-173 may have a therapeutic value as an enhancer or an anticancer drug.
•Tumor vessels are leaky and immature, which causes poor oxygen and nutrient supply, resulting in cancer cell metastasis.•HS-173 caused vessel normalization in tumors, inhibiting vascular leakage and neoangiogenesis.•In combination therapy, HS-173 increased blood perfusion and led to delayed tumor growth.•Vessel normalization by HS-173 could be a novel therapeutic strategy for inhibiting tumor growth by improving drug delivery.
Mesoporous metal oxides exhibit excellent physicochemical properties and are widely used in various fields, including energy storage/conversion, catalysis, and sensors. Although several soft‐template ...approaches are reported, high‐temperature calcination for both metal oxide formation and template removal is necessary, which limits direct synthesis on a plastic substrate for flexible devices. Here, a universal synthetic approach that combines thermal activation and oxygen plasma to synthesize diverse mesoporous metal oxides (V2O5, V6O13, TiO2, Nb2O5, WO3, and MoO3) at low temperatures (150–200 °C), which can be applicable to a flexible polymeric substrate is introduced. As a demonstration, a flexible micro‐supercapacitor is fabricated by directly synthesizing mesoporous V2O5 on an indium‐tin oxide‐coated colorless polyimide film. The energy storage performance is well maintained under severe bending conditions.
The synergistic effect of thermal activation and plasma enabled low‐temperature synthesis (150–200 °C) of various mesoporous metal oxide (V2O5, V6O13, TiO2, WO3, Nb2O5, and MoO3), suitable for flexible polymeric substrates. As a proof of concept, the direct synthesis of mesoporous V2O5 is demonstrated on an indium‐tin oxide‐coated polyimide film and its application as electrode materials.
MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using ...LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the loss of miR-155 hampers glucose uptake and glycolysis, via the down-regulation of glucose transporters and metabolic enzymes including HK2, PKM2, and LDHA. We showed this is due to the down-regulation of cMYC, controlled through phosphoinositide-3-kinase regulatory subunit alpha (PIK3R1)-PDK1/AKT-FOXO3a pathway. UTR analysis of the PIK3R1 and FOXO3a indicated miR-155 directly represses these genes. A stable expression of miR-155 in patient-derived cells (PDCs) showed activated glucose metabolism whereas a stable inhibition of miR-155 reduced in vivo tumor growth with retarded glucose metabolism. Furthermore, analysis of 50 triple-negative breast cancer (TNBC) specimens and specific uptake value (SUV) of PET images revealed a positive correlation between miR-155 level and glucose usage in human breast tumors via PIK3R1-PDK/AKT-FOXO3a-cMYC axis. Collectively, these data demonstrate the miR-155 is a key regulator of glucose metabolism in breast cancer.
To facilitate rapid determination of cellular viability caused by the inhibitory effect of drugs, numerical deep learning algorithms was used for unlabeled cell culture images captured by a light ...microscope as input. In this study, A549, HEK293, and NCI-H1975 cells were cultured, each of which have different molecular shapes and levels of drug responsiveness to doxorubicin (DOX). The microscopic images of these cells following exposure to various concentrations of DOX were trained with the measured value of cell viability using a colorimetric cell proliferation assay. Convolutional neural network (CNN) models for the study cells were constructed using augmented image data; the predicted cell viability using CNN models was compared to the cell viability measured by colorimetric assay. The linear relationship coefficient (r
) between measured and predicted cell viability was determined as 0.94-0.95 for the three cell types. In addition, the measured and predicted IC50 values were not statistically different. When drug responsiveness was estimated using allogenic models that were trained with a different cell type, the correlation coefficient decreased to 0.004085-0.8643. Our models could be applied to label-free cells to conduct rapid and large-scale tests while minimizing cost and labor, such as high-throughput screening for drug responsiveness.
Exacerbation of inflammatory bowel disease (IBD) is common. Identification of the exacerbating factors could facilitate interventions for forecastable environmental factors through adjustment of the ...patient's daily routine. We assessed the effect of natural environmental factors on the exacerbation of IBD.
In this systematic review and meta-analysis, studies published from January 1, 1992 to November 3th, 2022 were searched in the MEDLINE, Embase, CINAHL Complete and Cochrane Library databases. We extracted data related to the impact of environmental variations on IBD exacerbation, and performed a meta-analysis of the individual studies' correlation coefficient χ2 converted into Cramér's V (φc) with 95% confidence intervals (CI).
A total of 7,346 publications were searched, and 20 studies (sample size 248-84,000 cases) were selected. A meta-analysis with seven studies was performed, and the pooled estimate of the correlation (φc) between the seasonal variations and IBD exacerbations among 4806 cases of IBD exacerbation was 0.11 (95% CI 0.07-0.14; I2 = 39%; p = 0.13). When divided into subtypes of IBD, the pooled estimate of φc in ulcerative colitis (six studies, n = 2649) was 0.07 (95% CI 0.03-0.11; I2 = 3%; p = 0.40) and in Crohn's disease (three studies, n = 1597) was 0.12 (95% CI 0.07-0.18; I2 = 18%; p = 0.30).
There was a significant correlation between IBD exacerbation and seasonal variations, however, it was difficult to synthesize pooled results of other environmental indicators due to the small number of studies and the various types of reported outcome measures. For clinical implications, additional evidence through well-designed follow-up studies is needed.
CRD42022304916.
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