KEGG: biological systems database as a model of the real world.

KEGG (https://www.kegg.jp/) is a database resource for representation and analysis of biological systems. Pathway maps are the primary dataset in KEGG representing systemic functions of the cell and the organism in terms of molecular interaction and reaction networks. The KEGG Orthology (KO) system is a mechanism for linking genes and proteins to pathway maps and other molecular networks. Each KO is a generic gene identifier and each pathway map is created as a network of KO nodes. This architecture enables KEGG pathway mapping to uncover systemic features from KO assigned genomes and metagenomes. Additional roles of KOs include characterization of conserved genes and conserved units of genes in organism groups, which can be done by taxonomy mapping. A new tool has been developed for identifying conserved gene orders in chromosomes, in which gene orders are treated as sequences of KOs. Furthermore, a new dataset called VOG (virus ortholog group) is computationally generated from virus proteins and expanded to proteins of cellular organisms, allowing gene orders to be compared as VOG sequences as well. Together with these datasets and analysis tools, new types of pathway maps are being developed to present a global view of biological processes involving multiple organism groups.

Performance Evaluation of Commonly Used Portable Hemoglobin Sensors in Comparison to Clinical Test Results.

Telehealth systems in underserved countries leverage various low-cost portable medical sensors to transmit patients' vital information to remote doctors, facilitating timely diagnoses and interventions. However, the potential risks associated with inaccurate data pose considerable threats to the health of individuals. This study focuses on identifying high-quality portable hemoglobin sensors, employing the Japanese clinical pathology laboratory as a gold standard. Out of the eight sensors evaluated in this study, four were found to be highly erroneous.

Heat Shock Related Protein Expression in Abdominal Testes of Asian Elephant (Elephas maximus).

The abdominal testes of Asian elephants show normal spermatogenesis. Heat shock in cryptorchid testes elevates heat shock factor (HSF) expression, leading to germ cell apoptosis, while increased heat shock proteins (HSPs) levels provide protection. To investigate how heat shock affects elephant spermatogenic cells, focusing on heat shock-related molecules and the cell death mechanism, immunohistochemistry and TUNEL staining were employed to assess the immunoexpression of several heat shock-related molecules and the status of apoptosis in elephant fibroblasts (EF) induced by heat shock stimulus. Additionally, the immunoexpression of heat shock-related molecules and cell proliferation status in the elephant spermatogenic cells. Our finding indicated that heat shock-induced HSF1 immunoexpression in EF leads to apoptosis mediated by T-cell death-associated gene 51 (TDAG51) while also upregulating HSP70 to protect damaged cells. In elephant spermatogenic cells, immunostaining revealed a predominance of proliferating cell nuclear antigen (PCNA)-positive cells with minimal TDAG51- and TUNEL-positive cells, suggesting active proliferation and apoptosis suppression during normal spermatogenesis in the abdominal testis. Interestingly, spermatogonia co-immunoexpressed HSF1 and HSP90, potentially reducing apoptosis through protective mechanisms different from those observed in other mammals. Spermatogenic cells did not show immunolocalisation of HSP70, and hence, it may not contribute to protecting the spermatogonia from heat shock because the transcriptional activity of HSF1 is suppressed by HSP90A binding. This study provides insight into the specific heat shock response and defence mechanisms in elephant spermatogenic cells and may contribute to our understanding of species-specific adaptation to environmental stresses of the testis.

Comparison between the sodium chloride content and labeled salt value of industrially prepared Japanese single dishes.

Salt intake reduction is a global concern. In particular, Japanese consume higher amounts of salt than those of other ethnicities. The sodium content is mentioned on the label of industrially prepared dishes with an intention of reducing salt intake. This study aimed to evaluate the difference between the actual sodium content and labeled salt value of industrially prepared Japanese single dishes. Samples labeled "estimated" were collected and classified as Japanese, Western, and Chinese cuisines. The sodium content ranged from 180 to 1011 mg/100 g. The sodium content was higher than their reported values in other countries. Specifically, Chinese dishes contained high amounts of sodium, although the chloride content was similar across cuisine styles. Further, the molar ratio (i.e., sodium/chloride) had no significant effect on the difference between the actual content and labeled value. The measured salt contents were 20% higher than the labeled values. The results of decision tree analysis indicated that if the labeled salt value of stir-fried foods is determined by calculation, the actual sodium content is much higher than the labeled salt value. These findings are crucial for customers, dietitian, and researchers as they refer to the labeled salt value to determine the sodium content of industrially prepared foods.

Effect of an Internet-based mental health promotion intervention among immigrant Chinese women: A quasi-experimental study.

Background: Owing to a lack of social support, child-rearing Chinese women in Japan experience mental health disorders, such as depression and parenting stress. Effective interventions to improve the mental health of these women are lacking. This study aimed to develop an Internet-based mental health promotion intervention for this subsection of the population and evaluate the effectiveness of the intervention. Methods: We used a quasi-experimental pre- and post-test design whereby the results of the intervention group were compared with those of a control group. Seventy-three child-rearing women were recruited from online groups of Chinese residents in Japan. In the Internet-based intervention, participants utilised an information provision application and attended online parenting workshops. The intervention group participated in the online workshops once a week for six weeks and accessed the application, whereas the control group did not. The outcome measures included the levels of mental health distress, depression, social support, and parenting stress. Data were collected from February to April 2022. Data analysis was performed using repeated-measures analysis of variance. Results: Mental health distress (F = 16.478, p < 0.001, η2 = 0.210) and depression (F = 13.078, p = 0.001, η2 = 0.174) were significantly affected in the intervention group compared with the control group. There were no significant differences in social support and parenting stress between the groups. The Internet-based mental health promotion intervention was highly appraised by the participants. Conclusions: This study developed an Internet-based mental health promotion intervention that involved an information provision application and parenting workshops. The intervention significantly reduced the mental health distress and depression of Chinese women in Japan but did not affect social support and parenting stress. The findings suggest that this intervention could be applied to foreign women with multicultural backgrounds in diverse settings to improve their psychological well-being.

Association Between Gestational Weeks, Initial Maternal Perception of Fetal Movement, and Individual Interoceptive Differences in Pregnant Women: Cross-Sectional Study.

BACKGROUND: Interoception encompasses the conscious awareness of homeostasis in the body. Given that fetal movement awareness is a component of interoception in pregnant women, the timing of initial detection of fetal movement may indicate individual differences in interoceptive sensitivity. OBJECTIVE: The aim of this study is to determine whether the association between the gestational week of initial movement awareness and interoception can be a convenient evaluation index for interoception in pregnant women. METHODS: A cross-sectional study was conducted among 32 pregnant women aged 20 years or older at 22-29 weeks of gestation with stable hemodynamics in the Obstetric Outpatient Department. Interoception was assessed using the heartbeat-counting task, with gestational weeks at the first awareness of fetal movement recorded via a questionnaire. Spearman rank correlation was used to compare the gestational weeks at the first awareness of fetal movement and heartbeat-counting task scores. RESULTS: A significant negative correlation was found between the gestational weeks at the first fetal movement awareness and heartbeat-counting task performance among all participants (r=-0.43, P=.01) and among primiparous women (r=-0.53, P=.03) but not among multiparous women. CONCLUSIONS: Individual differences in interoception appear to correlate with the differences observed in the timing of the first awareness of fetal movement.

Metabolically healthy obesity and risks of cardiovascular disease and all-cause mortality, a matched cohort study: the Shizuoka study.

BACKGROUND: Metabolically healthy obesity is not always a benign condition. It is associated with an increased incidence of cardiovascular disease and all-cause mortality. We investigated the prognostic significance of metabolically healthy obesity by comparing clinical profile-matched metabolically healthy obesity and non-obesity groups. METHODS: We analyzed a health insurance dataset with annual health checkup data from Japan. The analyzed data included 168,699 individuals aged <65 years. Obesity was defined as ≥25 kg/m2 body mass index. Metabolically healthy was defined as ≤1 metabolic risk factor (high blood pressure, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, or high hemoglobin A1c). Incidence rates of stroke, myocardial infarction, and all-cause mortality identified from the insurance data were compared between metabolically healthy obesity and non-obesity groups (n = 8644 each) using a log-rank test. RESULTS: The stroke (obesity: 9.2 per 10,000 person-years; non-obesity: 10.5; log-rank test p = 0.595), myocardial infarction (obesity: 3.7; non-obesity: 3.1; p = 0.613), and all-cause mortality (obesity: 26.6; non-obesity: 23.2; p = 0.304) incidence rates did not differ significantly between the metabolically healthy obesity and non-obesity groups, even when the abdominal obesity was considered in the analysis. The lack of association was also observed in the comparison between the metabolically unhealthy obesity and non-obesity groups (n = 10,965 each). The population with metabolically healthy obesity reported negligibly worse metabolic profiles than the population with non-obesity at the 5.6-year follow-up. CONCLUSION: Obesity, when accompanied by a healthy metabolic profile, did not increase the risk of cardiovascular outcomes and all-cause mortality.

Additive association of blood pressure and short stature with stroke incidence in 450,000 Japanese adults: the Shizuoka study.

Short stature was suggested to be a risk factor for cardiovascular events. Because short stature increases central blood pressure, this study aimed to investigate a longitudinal association between short stature, blood pressure, and incidence of cardiovascular disease by the analysis of insurance-based real-world dataset. We analyzed data from 463,844 adults aged 40 or older with a mean age of 66.7 enrolled in National Health Insurance, excluding individuals who experienced a stroke or myocardial infarction, or required long-term care. Data from annual health checkups were used to obtain baseline clinical information. Comorbidities and incidences of stroke and myocardial infarction were obtained from the insurance data. During a 5.5-year follow-up period, we observed 11,027 cases of stroke. Adults of a short stature exhibited a higher incidence rate in both men (≤155 cm: 99.7, >175 cm: 24.4) and women (≤140 cm: 85.9, >160 cm: 13.7). Although those in the short stature group had higher blood pressure, and often took antihypertensive drugs, the inverse association between height and stroke incidence was independent of these factors (hazard ratio for 5 cm shorter in height; men: 1.06 [1.03-1.09], women: 1.11 [1.06-1.13]). Short stature and blood pressure showed additive association with stoke incidence (log-rank p < 0.001). No significant association was observed with myocardial infarction (men: 1.01 [0.95-1.06], women: 1.06 [0.98-1.14]). In a longitudinal analysis of a large general Japanese population, short stature was linked to an increased risk of stroke in both genders in any blood pressure range.

[Optimal search conditions for identification of patients with chronic myeloid leukemia from Japanese National Health Insurance data].

This study investigated which conditions could be used to identify patients with chronic myeloid leukemia (CML) from a National Health Insurance claims dataset. During April 2012 and September 2018, 1,789,462 employees were enrolled in the dataset for Shizuoka Prefecture residents. The number of patients with the ICD-10 code for CML was 761. Among them, 246 who had been prescribed a tyrosine kinase inhibitor were considered as having true CML. The positive predictive value was calculated as 32.3% when CML was identified by ICD-10 code alone. Combination of ICD-10 code with prescribed drugs was required to accurately identify patients with CML from the insurance database.

Exploring nurses' clinical judgment concerning the relative importance of fall risk factors: A mixed method approach using the Q Methodology.

BACKGROUND: Nurses are pivotal in averting patient falls through their assessment of cues presented by patients and their environments, rendering clinical judgments regarding the risk of falling, and implementing tailored interventions. Despite the intricate cognitive processes entailed in nurses' judgment, no prior studies have explored their approach to assessing the risk of falling. OBJECTIVE: This study aimed to examine how nurses judge the risk of falling among patients with different conditions, whether there are differences in the importance of risk factors as judged by nurses, how they justify their judgments, and what attributes of the nurses influence their judgments. DESIGN: A mixed method approach using the Q Methodology was employed. SETTING(S): Three public and private hospitals in Japan. PARTICIPANTS: Eighteen nurses participated in the study. METHODS: Participants were tasked with ranking 36 patient scenarios, each featuring a distinct set of fall risk factors. Subsequently, post-sorting interviews were conducted to gather insights into their typical approach to assessing fall risk and the rationale behind their ranking decisions. A by-person principal component factor extraction was employed to examine differences in the rankings of the scenarios. The interview data were analyzed descriptively to elucidate the reasons behind these discrepancies. RESULTS: Nurses engage in complex cognitive manipulations when evaluating the risk of patient falls, drawing extensively from their wealth of experience while utilizing assessment tools to support their judgments. In essence, nurses identify patients' tendency to act alone without calling a nurse, impaired gait and cognition, sedative use, drains, and limited information sharing among healthcare professionals as key fall risks. In addition, nurses vary in the importance they attribute to certain risk factors, leading to the discrimination of three distinct judgment profiles. One group of nurses judges patients with cognitive impairment and acting alone as high risk. Another group of nurses considers patients with unstable gait and acting alone as high risk. The last group of nurses sees patients wearing slippers as high risk. The post-sorting interviews revealed that their judgments are closely related to the healthcare context and patient population. CONCLUSIONS: Nurses operate within diverse contexts, wherein they interact with patients of varying characteristics, collaborate with professionals from diverse disciplines, and have access to varying levels of human and physical resources. This nuanced understanding empowers the formulation of judgments that are finely attuned to the specific context at hand. STUDY REGISTRATION: Not registered.

Performance Evaluation of the Commonly-Used Portable Cholesterol Sensors for Telehealth Services in the Unreached Communities.

Portable medical sensors play an important role in healthcare services, especially in rural communities. Many telehealth systems use these devices for providing patients' vital information from a distance to remote doctors. Erroneous data will not only mislead the remote doctor for correct diagnosis but it will cause health threats to these unreached community people. Therefore, it is very important to identify good sensors with an acceptable level of accuracy but within the affordable price of the available sensors in the market. This study aims to identify quality portable cholesterol sensors with high accuracy with the reference of the Japanese clinical pathology laboratory as a gold standard. We have considered cholesterol sensors that measure total cholesterol for this study that are commonly used in the developing countries of Asia. We found that out of four, three of them were very much erroneous and cannot be recommended even for primary healthcare.

Association of Eicosapentaenoic and Docosahexaenoic Acid Intake with Low Birth Weight in the Second Trimester: The Japan Pregnancy Eating and Activity Cohort Study.

This study examined the association of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during the second trimester with low birth weight (LBW) in pregnant Japanese women and was conducted in conjunction with the Japan Pregnancy Eating and Activity Cohort (J-PEACH) study. The study included 504 pregnant women from four Japanese sites. During the second trimester (14-27 weeks), the participants filled out a self-administered questionnaire assessing the frequency of DHA and EPA supplement intake in the past month, as well as a brief-type self-administered diet history questionnaire (BDHQ). The analysis involved data from two time points: responses to the BDHQ and infant data at birth. In total, 471 and 33 participants were classified into the normal birth weight and LBW groups, respectively. The participants were divided into high-, medium-, and low-intake groups based on their total dietary and EPA and DHA supplementary intakes. The Cochran-Armitage trend test was used to analyze the data; the prevalence of LBW was higher in the low-intake group (p = 0.04). There was no significant sex-based trend (p = 0.27 and p = 0.35). In Japanese women, low dietary and supplementary EPA and DHA intake until the second trimester were risk factors for LBW.

Selenoneine Is Methylated in the Bodies of Mice and then Excreted in Urine as Se-Methylselenoneine.

Oral intake of purified selenoneine and seafoods has been reported to result in selenoneine accumulation in erythrocytes in mice and human. In addition, Se-methylselenoneine was suggested to be produced as a metabolite of selenoneine in the urine and whole blood of humans. In order to confirm the molecular mechanism of production of Se-methylselenoneine, a stable isotope (Se-76) labeled selenoneine was biosynthesized using genetically modified fission yeast and administered to mice. The Se-76-labeled Se-methylselenoneine was detected in urine but Se-78 and Se-80-labeled Se-methylselenoneine arising from natural isotopes of Se was hardly detected. These results suggest that Se-methylselenoneine was a metabolite and the excreted form of selenoneine. The methylation of selenoneine in mice administered selenoneine continuously was evaluated by the analyses of organs using an online liquid chromatograph system with an inductively coupled plasma mass spectrometer (LC-ICP-MS). These experiments indicate that selenoneine is methylated in the liver and (or) kidneys.

Longitudinal analysis of long-term outcomes of colorectal cancer after laparotomy and laparoscopic surgery: The Shizuoka study.

BACKGROUND: Long-term cancer prognosis after initial surgical procedures is an unlikely endpoint for clinical trials. Medical claim databases may aid in addressing this issue regardless of limited information on disease and patient background. However, the long-term prognosis (especially regarding long-term care needs) following surgical procedures remains unclear. This study aimed to assess whether long-term outcomes, such as the exacerbation of long-term care needs and mortality, differ with surgical methods. METHODS: Using a longitudinal study with linkage between medical claim and long-term care database, patients with primary colorectal cancer who underwent initial colonoscopies were identified through anonymized data in Japan (Shizuoka Kokuho Database, 2012-2018). Odds ratios (ORs) for long-term outcomes (long-term care needs and all-cause mortality during a 6.5-year follow-up period) were analyzed using logistic regression to compare laparoscopy and endoscopic surgery to laparotomy. RESULTS: Overall, 3,744 primary colorectal cancer cases (822 laparotomies, 705 laparoscopies, and 2,217 endoscopic surgeries) were included. Compared to the laparotomy group, the crude OR for exacerbation of long-term care needs in the laparoscopic surgery group was 0.376 (95% confidence interval, 0.227, 0.624), while the OR for all-cause mortality was 0.22 (0.329, 0.532). CONCLUSION: This is the first study to analyze long-term prognosis after surgery for patients with colorectal cancer to combine medical and long-term needs data. As the national health insurance claim database rarely includes information on cancer stage and comorbidities, better prognosis on endoscopic surgery may need careful interpretation. Therefore, laparoscopy has superior outcomes in terms of long-term care needs and mortality compared to those of laparotomy.

Distribution and Effects of Selenoneine by Ingestion of Extract from Mackerel Processing Residue in Mice.

Selenoneine is an organic selenium compound contained in blood and dark muscle of fish. It has a strong antioxidative capacity and is considered useful as a new functional food material. However, the distribution and effects of selenoneine in the mammalian body have not been thoroughly examined. In this study, a selenoneine-rich mackerel extract was developed and fed to mice at 0.07% in standard rodent chow (ME diet) for 32 days to examine its distribution in the body. Selenoneine was distributed in the liver, kidney, and spleen in mice fed with mackerel extract, but it was not distributed in the plasma or erythrocytes. Moreover, concentrations of the major selenium-containing protein were not affected by the mackerel extract. The results of this study suggest that selenoneine is absorbed in the body following ingestion of low doses in crude material and preferentially accumulates in organs and later distributes in erythrocytes. Biochemical analyses of plasma in male mice showed that the glucose level was significantly increased and LDL-cholesterol level was significantly decreased by ME diet feeding. The results indicate that male mice are sensitive to ME diet.

Natto extract inhibits infection caused by the Aujeszky's disease virus in mice.

Aujeszky's disease virus (ADV), also known as Suid alphaherpesvirus 1, which mainly infects swine, causes life-threatening neurological disorders. This disease is a serious global risk factor for economic losses in the swine industry. The development of new anti-ADV drugs is highly anticipated and required. Natto, a traditional Japanese fermented food made from soybeans, is a well-known health food. In our previous study, we confirmed that natto has the potential to inhibit viral infections by severe acute respiratory syndrome coronavirus 2 and bovine alphaherpesvirus 1 through their putative serine protease(s). In this study, we found that an agent(s) in natto functionally impaired ADV infection in cell culture assays. In addition, ADV treated with natto extract lost viral infectivity in the mice. We conducted an HPLC gel-filtration analysis of natto extract and molecular weight markers and confirmed that Fraction No. 10 had ADV-inactivating ability. Furthermore, the antiviral activity of Fraction No. 10 was inhibited by the serine protease inhibitor 4-(2-Aminoethyl) benzene sulfonyl fluoride hydrochloride (AEBSF). These results also suggest that Fraction No. 10, adjacent to the 12.5 kDa peak of the marker in natto extract, may inactivate ADV by proteolysis. Our findings provide new avenues of research for the prevention of Aujeszky's disease.

Recent Advances in In Vivo Somatic Cell Gene Modification in Newborn Pups.

Germline manipulation at the zygote stage using the CRISPR/Cas9 system has been extensively employed for creating genetically modified animals and maintaining established lines. However, this approach requires a long and laborious task. Recently, many researchers have attempted to overcome these limitations by generating somatic mutations in the adult stage through tail vein injection or local administration of CRISPR reagents, as a new strategy called "in vivo somatic cell genome editing". This approach does not require manipulation of early embryos or strain maintenance, and it can test the results of genome editing in a short period. The newborn is an ideal stage to perform in vivo somatic cell genome editing because it is immune-privileged, easily accessible, and only a small amount of CRISPR reagents is required to achieve somatic cell genome editing throughout the entire body, owing to its small size. In this review, we summarize in vivo genome engineering strategies that have been successfully demonstrated in newborns. We also report successful in vivo genome editing through the neonatal introduction of genome editing reagents into various sites in newborns (as exemplified by intravenous injection via the facial vein), which will be helpful for creating models for genetic diseases or treating many genetic diseases.

KEGG tools for classification and analysis of viral proteins.

The KEGG database and analysis tools (https://www.kegg.jp) have been developed mostly for understanding genes and genomes of cellular organisms. The KO (KEGG Orthology) dataset, which is a collection of functional orthologs, plays the role of linking genes in the genome to pathways and other molecular networks, enabling KEGG mapping to uncover hidden features in the genome. Although viruses were part of KEGG for some time, they were not fully integrated in the KEGG analysis tools, because the KO assignment rate is very low for virus genes. To supplement KOs a new dataset named virus ortholog clusters (VOCs) is computationally generated, covering 90% of viral proteins in KEGG. VOCs can be used, in place of KOs, for taxonomy mapping to uncover relationships of sequence similarity groups and taxonomic groups and for identifying conserved gene orders in virus genomes. Furthermore, selected VOCs are used to define tentative KOs for characterizing protein functions. Here an overview of KEGG tools is presented focusing on these extensions for viral protein analysis.