Human volitional actions are preceded by preparatory processes, a critical mental process of cognitive control for future behavior. Volitional action preparation is regulated by large-scale neural circuits including the cerebral cortex and the basal ganglia. Because volitional action preparation is a covert process, the network dynamics of such neural circuits have been examined by neuroimaging and recording event-related potentials. Here, we examined whether such covert processes can be measured by the overt responses of fixational saccades (including microsaccades), the largest miniature eye movements that occur during eye fixation. We analyzed fixational saccades while adult humans maintained fixation on a central visual stimulus as they prepared to generate a volitional saccade in response to peripheral stimulus appearance. We used the antisaccade paradigm, in which subjects generate a saccade toward the opposite direction of a peripheral stimulus. Appropriate antisaccade performance requires the following two aspects of volitional control: 1) facilitation of saccades away from the stimulus and 2) suppression of inappropriate saccades toward the stimulus. We found that fixational saccades that occurred before stimulus appearance reflected the dual preparatory states of saccade facilitation and suppression and correlated with behavioral outcome (i.e., whether subjects succeeded or failed to cancel inappropriate saccades toward the stimulus). Moreover, fixational saccades explained a large proportion of individual differences in behavioral performance (poor/excellent) across subjects. These results suggest that fixational saccades predict the outcome of future volitional actions and may be used as a potential biomarker to detect people with difficulties in volitional action preparation.
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.
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.
Background: Acrylamide has been classified as a probable human carcinogen based chiefly on laboratory evidence. However, the influence of dietary acrylamide intake on risk of esophageal, gastric, and colorectal cancer has not been extensively studied. We aimed to evaluate the association between dietary acrylamide intake and esophageal, gastric, and colorectal cancer using data from the Japan Public Health Center-based Prospective Study. Methods: Our study included 87,628 participants who completed a food-frequency questionnaire at enrollment in 1990 and 1993. We used Cox proportional hazards regression models to estimate hazards ratios and 95% confidence intervals (CI) after adjusting for confounding factors. Results: After 15.5, 15.3, and 15.3 mean years of follow-up for esophageal, gastric, and colorectal cancer, we identified and analyzed 391 esophageal, 2,218 gastric, and 2,470 colo-rectal cancer cases, respectively. Compared with the lowest quintile of acrylamide intake, the multivariate HR for the highest quintile was 0.86 (95% CI, 0.53-1.39; P trend ¼ 0.814), 0.84 (95% CI, 0.69-1.01; P trend ¼ 0.301), and 0.93 (95% CI, 0.79-1.08; P trend ¼ 0.165) for esophageal, gastric, and colorectal cancer, respectively, in the multivariableadjusted model. Furthermore, no significant associations were observed when the participants were stratified by cancer subsites. Conclusions: In conclusion, this study demonstrated that dietary acrylamide intake was not associated with increased risk of esophageal, gastric, or colorectal cancer among the Japanese population. Impact: It is the first time to assess the effect of dietary acrylamide intake on risk of digestive system cancer in Asian populations.
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).
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