Microarray technology is a high-throughput method for measuring the expression levels of thousand of genes simultaneously. The observed intensities combine a non-specific binding, which is a major disadvantage with microarray data. The Affymetrix GeneChip assigned a mismatch (MM) probe with the intention of measuring non-specific binding, but various opinions exist regarding usefulness of MM measures. It should be noted that not all observed intensities are associated with expressed genes and many of those are associated with unexpressed genes, of which measured values express mere noise due to non-specific binding, cross-hybridization, or stray signals. The implicit assumption that all genes are expressed leads to poor performance of microarray data analyses. We assume two functional states of a gene - expressed or unexpressed - and propose a robust method to estimate gene expression states using an order relationship between PM and MM measures. An indicator 'probability of a gene being expressed' was obtained using the number of probe pairs within a probe set where the PM measure exceeds the MM measure. We examined the validity of the proposed indicator using Human Genome U95 data sets provided by Affymetrix. The usefulness of 'probability of a gene being expressed' is illustrated through an exploration of candidate genes involved in neuroblastoma prognosis. We identified the candidate genes for which expression states differed (un-expressed or expressed) when compared between two outcomes. The validity of this result was subsequently confirmed by quantitative RT-PCR. The proposed qualitative evaluation, 'probability of a gene being expressed', is a useful indicator for improving microarray data analysis. It is useful to reduce the number of false discoveries. Expression states - expressed or unexpressed - correspond to the most fundamental gene function 'On' and 'Off', which can lead to biologically meaningful results.

Cohort studies using large-scale databases have become increasingly important in recent years. The Tokushukai Medical Group is a leading medical group in Japan that includes 71 general hospitals nationwide from Hokkaido to Okinawa, with a total of 18,000 beds, and a unified electronic medical record system. This retrospective cohort study aims to evaluate the real-world outcomes of systemic therapy for Japanese patients with cancer using this merit of scale. All adult patients with cancer who received systemic therapy using a centrally registered chemotherapy protocol system at 46 hospitals from April 2010 to March 2020 will be identified (~48,850 patients). Key exclusion criteria include active double cancer and inadequate data extraction. Data will be obtained through electronic medical records, diagnosis procedure combination data, medical prescription data, and the national cancer registration system that includes sociodemographic variables, diagnostic and laboratory tests, concomitant drug prescriptions, cost, and overall survival. Kaplan–Meier estimates will be calculated for time-to-event analyses. Stratified/conventional Cox proportional hazards regression analyses will be conducted to examine the relationships between overall survival and related factors. Our findings provide important insights for future research directions, policy initiatives, medical guidelines, and clinical decision-making.

There are two types of exposure to atomic bomb (A-bomb) radiation: exposure to initial radiation released at the time of the detonation of the bomb, and exposure to residual radiation, which remains afterwards. Health hazards caused by exposure from residual radiation have not yet been clarified. The purpose of our study was to reveal the relationships between mortality risk from solid cancer and residual radiation based on data from the early entrants to Hiroshima. It is hard to identify the individual residual radiation doses. However, these are assumed to depend on the date of entry and the entrants’ behavior. Individual behavior is thought to be closely related to gender and age at exposure. We investigated a cohort of 45 809 individuals who were living in Hiroshima Prefecture on 1 January 1970 and were registered on the Database of Atomic Bomb Survivors as entrants after the bombing. Poisson regression methods were used to estimate excess relative risks (ERR) with data cross-classified by sex, age at entry, and date of entry. In males in their 20s, 30s, and 40s at entry and in females less than 10 years old and in their 40s at entry, solid cancer mortality risks were significantly higher among persons who entered the city on the day of the bombing than those who entered three or more days later. With adjustments for the age-dependent sensitivities to radiation exposure, it was extrapolated that middle-aged people who entered the city on the day of the bombing were exposed to higher levels of residual radiation than younger people.

At the detonation of the atomic bombing in Hiroshima and Nagasaki, a significant amount of radionuclides was produced by the neutron induced activation. The residual radiation from the explosion is crucial to the health risk of the people who entered these cities after the bombing and might have inhaled these radioactive materials. Because ⁵⁶Mn is one of the major radionuclides produced in soil and have not been studied until now, we had conducted a series of experiments using rats to investigate the biological impacts of exposure of ⁵⁶MnO₂ particles. In these experiments, the rats’ spontaneous locomotor activity was also assessed to examine the possible effects of ⁵⁶Mn on their behavior. However, the locomotor activity data obtained from an individual experiment failed to identify radiation effects due to the large variation among animals and the small sample size. In the present study, all available data from our previous studies on ⁵⁶MnO₂ exposure (0.02–0.15 Gy of whole-body doses) as well as ⁶⁰Co-γ exposure (at 2–5 Gy of whole-body doses) were pooled. Our statistical method, which takes into account individual differences and daily fluctuations, successfully identified a decrease in locomotor activity caused by ⁵⁶MnO₂ exposure, where the changes were gradual and reached the maximum reduction around 2 weeks after exposure. In contrast, exposure to ⁶⁰Co-γ rays produced the highest decline of activity within one day. These results suggest that internal exposure to ⁵⁶Mn at whole-body doses of even less than 0.15 Gy may have a long-lasting impact on locomotor activity.

Investigating initial behavioral changes caused by irradiation of animals might provide important information to aid understanding of early health effects of radiation exposure and clinical features of radiation injury. Although previous studies in rodents suggested that radiation exposure leads to reduced activity, detailed properties of the effects were unrevealed due to a lack of proper statistical analysis, which is needed to better elucidate details of changes in locomotor activity. Ten-week-old male Wistar rats were subjected to single point external whole-body irradiation with ⁶⁰Co gamma rays at 0, 2.0, 3.5, and 5.0 Gy (four rats per group). Infrared sensors were used to continuously record the locomotor activity of each rat. The cumulative number of movements during the night was defined as “activity” for each day. A non-linear mixed effects model accounting for individual differences and daily fluctuation of activity was applied to analyze the rats’ longitudinal locomotor data. Our statistical method revealed characteristics of the changes in locomotor activity after radiation exposure, showing that (1) reduction in activity occurred immediately—and in a dose-dependent manner—after irradiation and (2) recovery to pre-irradiation levels required almost one week, with the same recovery rate in each dose group.

Background/Objective: The Empty Spiracles Homeobox 2 (EMX2) gene is a homeobox transcription factor that is critical for the development of the central nervous system and genitourinary system during embryogenesis. EMX2 has been shown to regulate cellular differentiation, migration, and proliferation through its involvement in transcriptional control. Dysregulation of EMX2 expression has been implicated in various pathological conditions, including cancer, but the precise molecular mechanisms underlying EMX2 functions in cancer remain incompletely understood. In this study, we focus on the expression profile and the prognostic significance of EMX2 in esophageal squamous cell carcinoma (ESCC). Methods/Results: The expression levels of EMX2 in clinical ESCC samples varied and appeared to be lower than those in adjacent normal tissues. In addition, EMX2 expression was detected in some of the 20 ESCC cell lines but not in others and was correlated with 5-FU sensitivity. EMX2 expression in ESCC cell lines was strongly associated with colony formation capacity in soft agar, and EMX2 knockdown decreased colony formation. Enforced expression of EMX2 decreased the side population (SP) ratio in FACS analysis but increased colony formation in SP fractions. Although it is a preliminary experiment, xenograft in immunodeficient (NOD) scid mice suggested that the forced expression of EMX2 increased tumorigenic capacity in vivo. A Kaplan–Meyer analysis of patients from whom 20 ESCC cell lines or 18 ESCC tissue samples were obtained indicated that EMX2 expression was a poor prognostic marker. Conclusion: EMX2 has a unique function in ESCC stemness and its expression is the stamped marker of poor prognosis in ESCC patients.