Among the more than 170 known RNA modifications, methylation modification is the most frequent and well‐studied. Depending on where the methylation occurs, RNA methylation can be classified as ...N6‐methyladenosine, N1‐methyladenosine, 5‐methylcytosine, N7‐methylguanosine, and others. The methylation of RNA is constantly and dynamically modified in the complex microenvironment by methyltransferases, demethylases, and methylation reading proteins. These changes affect the proliferation and differentiation of immune cells as well as their effector activities by affecting RNA location, activity, stability, and translation efficiency. This review outlines how diverse RNA methylation alterations affect immune cell development and biological activity, as well as the role of RNA methylation in health and disease, to provide a molecular basis for future immunotherapies.
Background: Few cohort studies have used multiple surveys of screening attendance to simultaneously evaluate the effectiveness of fecal occult blood test (FOBT) and colonoscopy.Methods: We analyzed ...data of 30,381 middle-aged Japanese adults from a population-based prospective cohort study. Information on FOBT and colonoscopy was obtained from three questionnaire surveys (every 5 years). We classified the subjects into three groups: the FOBT (15,649 subjects), screening colonoscopy (2,407 subjects), and unscreened (12,325 subjects) groups. We used the unscreened group as the reference group to compare the mortality and incidence of colorectal cancer (CRC).Results: During the 14-year follow-up, 64, 12, and 104 CRC deaths were identified in the FOBT, screening colonoscopy, and unscreened groups, respectively. The risk of CRC death reduced with increasing the number of FOBTs (P for trend = 0.02) and was reduced by 44% in the subjects screened twice or thrice using FOBT (hazard ratio HR 0.56; 95% confidence interval CI, 0.33–0.94). Significant decreases were seen for the incidence of CRC but not seen for the incidence of non-advanced CRC in the FOBT group. Concerning the screening colonoscopy, subjects screened at the start of follow-up showed a 69% reduced risk of CRC death (HR 0.31; 95% CI, 0.10–0.9996). Significant decreases were also seen for the incidence of CRC and non-advanced CRC in the subjects screened at the start of follow-up.Conclusion: FOBT, depending on the number of FOBTs, and colonoscopy, depending on recency, reduced the risk of death due to CRC and the incidence of CRC.
Nucleocapsid protein (N protein) is the most abundant protein in SARS-CoV2 and is highly conserved, and there are no homologous proteins in the human body, making it an ideal biomarker for the early ...diagnosis of SARS-CoV2. However, early detection of clinical specimens for SARS-CoV2 remains a challenge due to false-negative results with viral RNA and host antibodies based testing. In this manuscript, a microfluidic chip with femtoliter-sized wells was fabricated for the sensitive digital detection of N protein. Briefly, β-galactosidase (β-Gal)-linked antibody/N protein/aptamer immunocomplexes were formed on magnetic beads (MBs). Afterwards, the MBs and β-Gal substrate fluorescein-di-β-d-galactopyranoside (FDG) were injected into the chip together. Each well of the chip would only hold one MB as confined by the diameter of the wells. The MBs in the wells were sealed by fluorocarbon oil, which confines the fluorescent (FL) product generated from the reaction between β-Gal and FDG in the individual femtoliter-sized well and creates a locally high concentration of the FL product. The FL images of the wells were acquired using a conventional inverted FL microscope. The number of FL wells with MBs (FL wells number) and the number of wells with MBs (MBs wells number) were counted, respectively. The percentage of FL wells was calculated by dividing (FL wells number) by (MBs wells number). The higher the percentage of FL wells, the higher the N protein concentration. The detection limit of this digital method for N protein was 33.28 pg/mL, which was 300 times lower than traditional double-antibody sandwich based enzyme-linked immunosorbent assay (ELISA).
An aptamer/antibody sandwich method for digital detection of SARS-CoV2 nucleocapsid protein based on microfluidic chip with femtoliter-sized wells was proposed for the first time. Display omitted
•A microfluidic chip was fabricated for the digital detection of SARS-CoV2 N protein.•An aptamer/antibody sandwich assay was used for the digital detection of N protein.•The digital detection limit for N protein was 300 times lower than traditional ELISA.•The usage of aptamer reduces the complexity and cost of the digital detection system.•The reusability of the PDMS-based chip reduces the experimental time.
Acrylamide forms during cooking and is classified as a probable carcinogen in humans, mandating the need for epidemiological studies of dietary acrylamide and cancers. However, the risk of dietary ...acrylamide exposure to breast cancer in Japanese women has not been assessed. We investigated the association between dietary acrylamide intake and risk of breast cancer in the Japan Public Health Center‐based Prospective Study. The present study included 48 910 women aged 45‐74 years who responded to a 5‐year follow‐up survey questionnaire. Dietary acrylamide intake was assessed using a validated food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. During an average of 15.4 years of follow up, 792 breast cancers were diagnosed. Energy‐adjusted dietary acrylamide intake was not associated with the risk of breast cancer (adjusted hazard ratio for highest versus lowest tertile = .95, 95% confidence intervals: 0.79‐1.14, P‐trend = .58). Further, no significant associations were observed when stratified analyses were conducted by smoking status, coffee consumption, alcohol consumption, body mass index, menopausal status, estrogen receptor status, and progesterone receptor status. In conclusion, dietary acrylamide intake was not associated with the risk of breast cancer in this population‐based prospective cohort study of Japanese women.
Acrylamide is classified as a probable carcinogen to humans, and diet is a considerable source of acrylamide exposure because it forms during cooking. However, there are no studies to assess the risk of dietary acrylamide not only in Japan but also in Asia. We investigated an association between dietary acrylamide intake and risk of breast cancer in a large prospective cohort study in Japan, but we did not identify any associations in Japanese women.
Upper gastrointestinal endoscopy for gastric cancer screening has been implemented in Japan. However, its effectiveness for gastric cancer prevention has not been fully studied. We aimed to ...investigate the effectiveness of endoscopic screening to reduce mortality from gastric cancer. In a large prospective population‐based cohort study including 80,272 participants, we compared the risk of mortality and incidence of gastric cancer among participants who underwent endoscopic or radiographic screening compared with those who did not undergo any screening using multivariable Cox proportional hazards models. In the 1,023,364 person‐year observation period (median; 13.0 years), 1977 cases of gastric cancer were diagnosed, and 783 patients with gastric cancer died. In the endoscopic screening group, the mortality from gastric cancer and incidence of advanced gastric cancer were reduced by 61% (hazard ratio HR = 0.39 95% CI: 0.30–0.51) and 22% (HR = 0.78 95% CI: 0.67–0.90), respectively. The radiographic screening reduced the mortality from gastric cancer (HR = 0.63 95% CI: 0.54–0.73), but its effectiveness was lower than that of endoscopic screening. In conclusion, endoscopic screening reduced the incidence of advanced gastric cancer and mortality from gastric cancer in the Japanese population.
In this Japanese prospective population‐based cohort study, endoscopic screening reduced the incidence of advanced gastric cancer by 22% and mortality from gastric cancer by 61% compared with no screening. The effectiveness of endoscopic screening on reducing gastric cancer mortality was greater than that of radiographic screening. The results provide a rationale for promoting endoscopic screening for gastric cancer, which has a high mortality rate and significant public health impact in Japan.
The 2011 Great East Japan Earthquake (within Fukushima, Iwate, and Miyagi prefectures) was a complex disaster; it caused a tsunami and the Fukushima Daiichi Nuclear Power Plant accident, resulting in ...radiation exposure. This study investigated the earthquake’s effects on the migration patterns of pregnant women and their concerns regarding radiation exposure. We also considered the following large-scale earthquakes without radiation exposure: Great Hanshin-Awaji (Hyogo prefecture), Niigata-Chuetsu, and Kumamoto. Pregnant women were categorized as outflow and inflow pregnant women. Data on the annual number of births three years before and after the earthquake were used as a denominator to calculate the outflow and inflow rates per 100 births. The odds ratios of annual outflow and inflow rates after the earthquake, using three years before the earthquake as the baseline, were calculated. The odds-ratio for outflow significantly increased for Hyogo, Fukushima, Miyagi, and Kumamoto prefectures after the earthquake, particularly for Fukushima, showing a significant increase until three years post the Great East Japan Earthquake (disaster year: odds-ratio: 2.66 95% confidence interval: 2.44–2.90, 1 year post: 1.37 1.23–1.52, 2 years post: 1.13 1.00–1.26, 3 years post: 1.18 1.05–1.31), while the remaining three prefectures reported limited increases post one year. The inflow decreased after the earthquake, particularly in Fukushima, showing a significant decrease until 2 years post the Great East Japan Earthquake (disaster year: 0.58 0.53–0.63, 1 year post: 0.76 0.71–0.82, 2 years post: 0.83 0.77–0.89). Thus, pregnant women’s migration patterns changed after large-scale earthquakes, suggesting radiation exposure concerns possibly have a significant effects. These results suggested that plans for receiving assistance and support that considers the peculiarities of disaster related damage and pregnant women’s migration patterns are needed in both the affected and non-affected areas.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A meta‐analysis published in 2015 noted a marginally increased risk of endometrial and ovarian cancers in non‐smoking women with dietary acrylamide intake, but only a few studies were included, and ...they were limited to Western countries. The aim of this study was to investigate the association between dietary acrylamide intake and endometrial or ovarian cancer risk in the Japan Public Health Center‐based Prospective Study (JPHC Study). In this prospective cohort study, 47 185 participants aged 45‐74 years at the follow‐up starting point in the JPHC Study were enrolled. Dietary acrylamide intake was assessed using a validated food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). In participants with endometrial and ovarian cancer, the average follow‐up periods were 15.5 and 15.6 years, respectively, and 161 and 122 cases of endometrial and ovarian cancer were diagnosed, respectively. Energy‐adjusted dietary acrylamide intake was negatively associated with endometrial cancer, but the association disappeared after adjusting for coffee consumption with an adjusted HR for the highest vs lowest tertile of 0.85 (95%CI: 0.54‐1.33). No association was observed, however, for ovarian cancer (adjusted HR, 0.77; 95%CI: 0.49‐1.23). Furthermore, after stratifying by smoking status, coffee consumption, alcohol consumption, body mass index, and menopause status, no association was observed. Dietary acrylamide intake was not associated with the risk of endometrial or ovarian cancer in Japanese women with a relatively lower dietary intake of acrylamide compared with Western populations.
Acrylamide is classified as a probable carcinogen to humans, and diet is a considerable source of acrylamide exposure because it forms during cooking. Given that no studies to assess the risk of dietary acrylamide on endometrial or ovarian cancers had been done in Japan, we investigated the association between dietary acrylamide intake and risk of endometrial or ovarian cancers in a large prospective cohort study in Japan, but did not identify any associations in Japanese women.
Background: Many epidemiological studies have investigated dietary intake of antioxidant vitamins in relation to prostate cancer risk in Western countries, but the results are inconsistent. However, ...few studies have reported this relationship in Asian countries.Methods: We investigated the association between intake of vitamins, including lycopene, α-carotene, β-carotene, vitamin C, vitamin E, with prostate cancer risk in the Japan Public Health Center-based Prospective (JPHC) study. 40,720 men without history of cancer finished the food frequency questionnaire (FFQ) and were included in the study. Hazard ratios (HRs) and 95% confidence intervals (CIs) of prostate cancer risk were calculated according to the quintiles of energy-adjusted intake of vitamins using Cox models.Results: After an average of 15.2 years (617,599 person-years in total) of follow-up, 1,386 cases of prostate cancer were identified, including 944 localized cases and 340 advanced cases. No associations were observed in consumption of antioxidant vitamins, including α-carotene, β-carotene, vitamin C, and vitamin E, and prostate cancer risk. Although higher lycopene intake was associated with increased risk of prostate cancer (highest vs lowest quintile, HR 1.24; 95% CI, 1.04–1.47; P for trend = 0.01), there was a null association of lycopene intake with risk of prostate cancer detected by subjective symptoms (HR 1.12; 95% CI, 0.79–1.58; P for trend = 0.11).Conclusion: Our study suggested no association between antioxidant intake of vitamins and prostate cancer risk.
•Radscore could be a significant predictor of SLN metastasis in invasive breast cancer.•Good performance of MSKCC nomogram for predicting SLN metastasis in invasive breast cancer.•The combination of ...radscore and MSKCC nomogram was significantly better than the MSKCC nomogram alone.
To develop a combined nomogram by incorporating the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram and ultrasound (US)-based radiomics score (Radscore) for predicting sentinel lymph node (SLN) metastasis in invasive breast cancer.
This retrospective study was approved by the ethics committee of our institution, and written informed consent was waived. A total of 452 patients with invasive breast cancer who received SLN Biopsy in a single center were included between January 2016 and December 2019. The patients were divided into a training set (n = 318) and a validation set (n = 134). A total of 1216 features were extracted from the regions of interest (ROIs) of the tumors on conventional ultrasound. The maximum relevance minimum redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) algorithm were used to build the Radscore. Afterward, the diagnostic performance was assessed and validated. Comparison of receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were performed to evaluate the incremental value of the combined model.
Obtained from 18 features, the Radscore indicated a favorable discriminatory capability in the training set with an area under the curve (AUC) of 0.834, whereas a value of 0.770 was observed in the validation set. The AUC of the combined model was 0.901 (95 % confidence interval (95 % CI): 0.865−0.938) in the training set and 0.833 (95 % CI: 0.788−0.878) in the validation set. Both of them were superior to MSKCC or imaging Radscore alone (P < 0.05). DCA demonstrated that the combined model was superior to the others in terms of clinical practicability.
Preoperative US-based Radscore can improve the accuracy of clinical MSKCC nomogram for SLN metastasis prediction in breast cancer.
Several studies have investigated the association between alcohol consumption and pancreatic cancer risk. However, these studies reported inconsistent results.
This study included 95,812 participants ...from the Japan Public Health Center-Based Prospective Study, whose alcohol drinking habit was collected through the questionnaire of the baseline survey in 1990 to 1994 for Cohort I and in 1993 to 1995 for Cohort II, and followed-up until December 2013. The hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable-adjusted Cox proportional hazard regression models.
During 1,969,101 person-years of follow-up, 598 patients (315 men and 283 women) were newly diagnosed with pancreatic cancer. No association was observed between alcohol consumption at baseline and pancreatic cancer risk in either men or women, even in the analyses conducted among men stratified by facial flushing responses or smoking status. When the population was limited to men whose alcohol drinking habit remained unchanged from the baseline survey to the 5-year follow-up survey, a significant association was observed in drinkers with alcohol consumption of 1 to 299 g/week compared with non/occasional drinkers (multivariable-adjusted HR, 1.73; 95% CI, 1.15-2.60).
A significant association between alcohol consumption and pancreatic cancer risk was observed when the population was limited to men with a 5-year unchanged alcohol drinking habit and was particularly strong in never smokers.
This study suggested an association between continuous alcohol consumption and pancreatic cancer risk in the Japanese population. However, further investigations using other cohort studies are required.
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