Predicting Cardiovascular Disease Mortality: Leveraging Machine Learning for Comprehensive Assessment of Health and Nutrition Variables.

Cardiovascular disease (CVD) is one of the primary causes of death around the world. This study aimed to identify risk factors associated with CVD mortality using data from the National Health and Nutrition Examination Survey (NHANES). We created three models focusing on dietary data, non-diet-related health data, and a combination of both. Machine learning (ML) models, particularly the random forest algorithm, demonstrated robust consistency across health, nutrition, and mixed categories in predicting death from CVD. Shapley additive explanation (SHAP) values showed age, systolic blood pressure, and several other health factors as crucial variables, while fiber, calcium, and vitamin E, among others, were significant nutritional variables. Our research emphasizes the importance of comprehensive health evaluation and dietary intake in predicting CVD mortality. The inclusion of nutrition variables improved the performance of our models, underscoring the utility of dietary intake in ML-based data analysis. Further investigation using large datasets with recurring dietary recalls is necessary to enhance the effectiveness and interpretability of such models.

Knowledge extraction from literature and enzyme sequences complements FBA analysis in metabolic engineering.

Flux balance analysis (FBA) using genome-scale metabolic model (GSM) is a useful method for improving the bio-production of useful compounds. However, FBA often does not impose important constraints such as nutrients uptakes, by-products excretions and gases (oxygen and carbon dioxide) transfers. Furthermore, important information on metabolic engineering such as enzyme amounts, activities, and characteristics caused by gene expression and enzyme sequences is basically not included in GSM. Therefore, simple FBA is often not sufficient to search for metabolic manipulation strategies that are useful for improving the production of target compounds. In this study, we proposed a method using literature and enzyme search to complement the FBA-based metabolic manipulation strategies. As a case study, this method was applied to shikimic acid production by Corynebacterium glutamicum to verify its usefulness. As unique strategies in literature-mining, overexpression of the transcriptional regulator SugR and gene disruption related to by-products productions were complemented. In the search for alternative enzyme sequences, it was suggested that those candidates are searched for from various species based on features captured by deep learning, which are not simply homologous to amino acid sequences of the base enzymes.

Identifying causes of death of companion dogs in Japan using data from pet cemeteries.

This study aimed to identify the causes of death in dogs that were buried at pet cemeteries. Using data obtained from a questionnaire completed by 5,118 dog owners from 1 April 2016 to 31 March 2017, we estimated the life expectancy and the odds ratio for principal causes of death using multiple logistic regression analysis with potential risk factors as independent variables. The life expectancy determined at birth was 13.98 years. The commonest cause of death was senility. The odds ratios of dying of senility being significantly higher in Labrador Retrievers and Shiba breeds and aged dogs, and significantly lower in Chihuahuas, dogs living indoors and neutered dogs.

Physical signs of canine cognitive dysfunction.

Physical disturbances are common in dogs with canine cognitive dysfunction (CCD). However, the relation between these physical disturbances and CCD has not been clarified. The aim of this study was to clarify the physical disturbances in CCD by questionnaire survey. The questionnaire consisted of items of general information, physical disturbances (gait and posture abnormalities, and deteriorating perception) and a CCD assessment scale named the CCD rating scale (CCDR). The survey was conducted toward owners of dogs aged 10 years or older in two ways: A web-based (Web survey) and a paper-based (Paper survey) survey. To determine which physical disturbances were associated with CCD, ordinal logistic regression analyzes were performed. Through the Web survey, 726 valid responses were obtained, and the test results revealed that vision impairment, smell disturbance, tremor, swaying or falling and head ptosis were significantly associated with CCD. These items, except for head ptosis, were also significantly associated with, or tended to be associated with, CCD in 103 valid responses to the Paper survey. The prevalence of CCD was increased in the elderly dog population, especially in dogs aged 16 years or older. In contrast, physical signs gradually increased from 10 years of age. These results suggest that physical disturbances may appear in the early stages of CCD. In conclusion, the present study revealed new clinical signs of CCD linked to physical disturbances and suggested that these signs could be useful for detecting early stage of CCD.

Evaluating the contact rate between companion dogs during dog walking and the practices towards potential cases of rabies among dog owners in Japan.

This study aimed to examine the habits of dog walking in Japan using an internet survey of insured dog owners. About 96.4% of the respondents (n = 1,151) reported that they would take their dogs for a walk and they most frequently walk their dogs once or twice a day (75.9%) for 30 min to 1 hr (83.1%). The probability of a companion dog having contact with other dogs during dog walking was estimated to be 0.83 (95% confidence interval [CI]: 0.81-0.85), and the associated daily contact rate was estimated using log-normal distribution with a mean of 2.73 (95% CI: 2.42-3.11) and a standard deviation (SD) of 6.39 (95% CI: 5.18-7.84). Multiple linear regression revealed that the contact rate is mainly influenced by the social behaviour of the owner and to a lesser degree by his/her demographic characteristics including the area of residence, the breed size of dog and the age of the owner. In addition, ten Likert items measured on a 5-point scale were designed to assess the practices towards potential cases of rabies among dog owners. The respondents (n = 972) achieved a mean score of 2.99 (out of a full score of 4) with a SD of 0.90 in responding to situations related to dog bite incidents and injury from stray cat scratches during dog walking. They achieved a higher score in responding to situations related to sighting a stray or wild animal during dog walking and situations related to non-specific clinical signs of rabies and bite injuries from stray dogs or wild animals during dog walking with a mean of 3.70 (SD = 0.58) and 3.84 (SD = 0.34), respectively. The level of best practice was also proved to be significantly associated with the demographic characteristics of the dog owner.

Evidence of genetic contribution to patellar luxation in Toy Poodle puppies.

Patellar luxation (PL) is one of the most common orthopedic disorders in dogs and a genetic factor is considered to play an important role in the development of PL. Genomic analysis has attempted to identify the genetic markers associated with the development of PL but only suggestive markers have been identified. Carefully selecting breeds with higher incidence rates of congenital PL as well as affected dogs with more severe symptoms are required, but such information remains limited to date. This study aimed to assess the genetic contribution to the development of PL in puppies. Using data on PL from 2,048 puppies of the nine common breeds in Japan, the association of PL grades between the limbs, breed, and sex as well as the concordance of PL between littermates were examined. A significant correlation was found between right and left limbs in PL grades in all the puppies (Spearman rank correlation coefficient (rs)=0.91, P<0.001) and for each breed (rs=0.81-0.93, P<0.001). In total, 20.3% of the puppies were affected. The inter-breed difference in PL prevalence was 2.1-38.1%, and Toy Poodles showed the highest prevalence rates. Littermates of the affected puppies with PL grade ≥2 had a 16.2-fold higher risk (P<0.001). Thus, these results suggest that PL in puppies is primarily influenced by genetics, especially in Toy Poodles. These data highlight the necessity of using a breeding scheme to decrease the prevalence of PL.

Activation of cell proliferation in Arabidopsis root meristem by isoprothiolane.

A plant growth regulating agent "Fuji-one" has been used to control non-parasitic damping-off (Murenae disease) of rice seedlings. Its active ingredient, isoprothiolane (diisopropyl 1,3-dithiolan-2-ylidenemalonate, IPT), enhances root elongation of rice and Arabidopsis. To understand the mechanisms of IPT's effect on root development, its effect on Arabidopsis root cells was investigated histologically. IPT at a lower concentration (12.5 µg/mL) had no effect on root cell elongation, whereas it enhanced cell division in the root meristem. Histological analysis using phytohormone-related mutants indicated that jasmonic acid and ethylene were involved in the enhanced cell division. In contrast, IPT at a higher concentration (75 µg/mL) suppressed both cell elongation and cell division, in which jasmonic acid and ethylene were not involved. In addition, root hair formation was suppressed by treatment with IPT. These analyses demonstrated that IPT (12.5 µg/mL) enhanced root elongation by activating cell division in a jasmonic acid- and ethylene-dependent manner.

Involvement of phytohormones in root elongation activity of isoprothiolane in Arabidopsis.

Isoprothiolane (diisopropyl 1,3-dithiolan-2-ylidenemalonate, IPT), an active ingredient of "Fuji-one," has been used as a plant growth regulating agent to control non-parasitic damping-off (MURENAE disease) of rice seedlings. To understant plant growth regulating activity of IPT, its effect on root development was investigated in Arabidopsis. IPT enhanced root elongation at a lower concentration (12.5 µg/mL) but suppressed it at a higher concentration (75 µg/mL). Analysis using phytohormone-related mutants and chemical inhibitors revealed that the enhancement of root elongation by IPT required auxin, jasmonic acid, and ethylene signal transduction. Activation of the signal transduction mediated by these three phytohormones was confirmed by gene expression analysis. More detailed mechanisms of IPT's effect on root development were demonstrated via investigation using Arabidopsis and chemical inhibitors.

Estimating the life expectancy of companion dogs in Japan using pet cemetery data.

The life expectancy provides valuable information about population health. The life expectancies were evaluated in 12,039 dogs which were buried or cremated during January 2012 to March 2015. The data of dogs were collected at the eight animal cemeteries in Tokyo. The overall life expectancy of dogs was 13.7 (95% confidence interval (CI): 13.7-13.8) years. The probability of death was high in the first year of life, lowest in the fourth year, and increased exponentially after four years of age like Gompertz curve in semilog graph. The life expectancy of companion dogs in Tokyo has increased 1.67 fold from 8.6 years to 13.7 years over the past three decades. Canine crossbreed life expectancy (15.1 years, 95% CI 14.9-15.3) was significantly greater than pure breed life expectancy (13.6 years, 95%CI 13.5-13.7, P-value <0.001). The life expectancy for male and for female dogs were 13.6 (95% CI: 13.5-13.7) and 13.5 (95% CI: 13.4-13.6) years, respectively, with no significant difference (P=0.097). In terms of the median age of death and life expectancy for major breeds, Shiba had the highest median age of death (15.7 years), life expectancy (15.5 years) and French Bulldog had the lowest median age of death (10.2 years), life expectancy (10.2 years). When considering life expectancy alone, these results suggest that the health of companion dogs in Japan has significantly improved over the past 30 years.

Toll-like receptors 2 and 3 enhance melanogenesis and melanosome transport in human melanocytes.

Because little is known about how the innate immune response influences skin pigmentation, we examined whether Toll-like receptor (TLR) agonists participate in melanogenesis and melanosome transportation. We observed that TLR2/2 agonist HKLM and TLR3 agonist Poly(I:C) increased the amount of extracellular melanin from primary human epidermal melanocytes. HKLM, but not Poly(I:C), increased the melanogenic genes such as tyrosinase and dopachrome tautomerase. Poly(I:C) increased the expression of Rab27A, a molecule that facilitates melanosome transport to perimembranous actin filament. UVB irradiation induced Rab27A and melanosome transportation in a similar manner of Poly(I:C). SiRNA for TLR3 or Rab27A suppressed the perimembranous accumulation of Gp100-positive vesicles in melanocytes and decreased melanin transfer to neighboring keratinocytes induced by both Poly(I:C) and UVB. These results suggest that the microenvironment in the epidermis and innate immune stimuli, such as microbiome and ultraviolet represented here by TLR2 and TLR3 agonists, could affect the melanogenesis in human melanocytes.

Angiographic Evaluation of Vascular Damage in Rat Liver After Administration of Epirubicin or Miriplatin.

BACKGROUND: Maintaining the function of blood vessels is important for the control of hepatocellular carcinoma (HCC) during treatment with repeated transcatheter arterial chemoembolization (TACE). This study was designed to compare the vascular damage caused by miriplatin (MPT), which has been commonly used for TACE, with the damage caused by epirubicin (EPI). MATERIALS AND METHODS: We used the portal vein of healthy rats for the administration of the drug (MPT or EPI) and/or soybean oil as vehicle. After 2 days, angiography was performed by X-ray computer tomography. RESULTS: The influence of soybean oil on blood vessel function was volume-dependent. EPI showed dose-dependent effects on angiography, and 0.5 mg EPI led to severe (grade 4) blood flow disturbance in all animals. The effect of 1 mg MPT on blood vessels was mild (grade 1) in all animals and not different from that of soybean oil alone. CONCLUSION: Less vascular damage is caused by MPT than by EPI, suggesting that MPT is a useful drug for TACE in HCC.

Association between age, breed and sex in relation to urinary disorders in insured cats in Japan during fiscal year 2012.

Data from 48,187 cats insured between April 2012 and March 2013 were analyzed using logistic regression analysis to determine the association of age, breed and sex with the occurrence of urinary disorders. The overall annual prevalence of urinary disorders was 12.2%. Using crossbreeds as the reference breed, Abyssinian cats had the highest odds of having urinary disorders with a ratio of 1.40 (95% confidence interval: 1.20-1.63), followed by Norwegian Forest Cats and Somalis. Male cats had higher odds of having urinary disorders with a ratio of 1.27 (1.20-1.35) over female cats. Older cats had higher odds of having urinary disorders than young cats.

Morbidity pattern by age, sex and breed in insured cats in Japan (2008-2013).

OBJECTIVES: The aim of the study was to describe the morbidity pattern of different diagnostic categories in insured cats in Japan by age, sex and breed. METHODS: The annual incidence rates of having at least one insurance claim were calculated overall and stratified by diagnosis, age, sex and breed using data from insured cats in the period April 2008 to March 2013. RESULTS: The overall annual incidence rate of having at least one insurance claim was 4632 (95% confidence interval 4608-4656) cats per 10,000 cat-years at risk. The highest annual incidence rate was obtained for digestive system disorders, followed by urinary tract disorders and dermatological disorders. The incidence rates varied between breeds for most diagnostic categories: for cardiovascular system disorders, Scottish Fold, American Shorthair, Persian, Maine Coon, Norwegian Forest Cat, Ragdoll and Bengal had a higher annual incidence rate than crossbreeds. CONCLUSIONS AND RELEVANCE: This study provides comparative and quantitative estimates of morbidity pattern in insured Japanese cats. These estimates can be utilised by veterinary practitioners, breeders and owners in diagnostic decision-making, breeding and when selecting a new pet, respectively.

Association between breed, gender and age in relation to cardiovascular disorders in insured dogs in Japan.

The association between breed, gender and age and cardiovascular disorders in the insured dog population in Japan was investigated, using multiple logistic regression analysis and data from 299,555 dogs insured between April 2010 and March 2011. The overall annual prevalence of cardiovascular disorder diagnosis was 2.1%. Using the Miniature Dachshund as the reference breed, Cavalier King Charles Spaniel had the highest odds of cardiovascular disorder with a ratio of 16.2 (95% confidence interval: 14.4-18.2), followed by Maltese, Pomeranian, Chihuahua and Shih Tzu. Male dogs had increased odds of 1.2 (1.1-1.3). The dogs had increased odds of having cardiovascular disorder by 1.5 times as their age increased by one year.

High resolution imaging of intracellular oxygen concentration by phosphorescence lifetime.

Optical methods using phosphorescence quenching by oxygen are suitable for sequential monitoring and non-invasive measurements for oxygen concentration (OC) imaging within cells. Phosphorescence intensity measurement is widely used with phosphorescent dyes. These dyes are ubiquitously but heterogeneously distributed inside the whole cell. The distribution of phosphorescent dye is a major disadvantage in phosphorescence intensity measurement. We established OC imaging system for a single cell using phosphorescence lifetime and a laser scanning confocal microscope. This system had improved spatial resolution and reduced the measurement time with the high repetition rate of the laser. By the combination of ubiquitously distributed phosphorescent dye with this lifetime imaging microscope, we can visualize the OC inside the whole cell and spheroid. This system uses reversible phosphorescence quenching by oxygen, so it can measure successive OC changes from normoxia to anoxia. Lower regions of OC inside the cell colocalized with mitochondria. The time-dependent OC change in an insulin-producing cell line MIN6 by the glucose stimulation was successfully visualized. Assessing the detailed distribution and dynamics of OC inside cells achieved by the presented system will be useful to understanding a physiological and pathological oxygen metabolism.

Comparison of energy metabolism and nutritional status of hospitalized patients with Crohn's disease and those with ulcerative colitis.

This study aimed to compare the nutritional status and energy expenditure of hospitalized patients with Crohn's disease (CD) and those with ulcerative colitis (UC). Twenty-two hospitalized patients with CD and 18 patients with UC were enrolled in this study. We analyzed nutritional status upon admission by using nutritional screening tools including subjective global assessment, malnutrition universal screening tool, and laboratory tests. We measured resting energy expenditure (mREE) of the patients with indirect calorimetry and predicted resting energy expenditure (pREE) was calculated by using the Harris-Benedict equation. Results presented here indicate no significant difference in nutritional parameters and energy metabolism between CD and UC patients. In UC patients, a significant correlation was observed between mREE/body weight and disease activity detected by the Lichtiger and Seo indices. However, there was no correlation between mREE/body weight and Crohn's disease activity index in CD patients. Inflammatory cytokine interleukin-6 levels correlated with mREE/pREE in CD and UC patients while tumor necrosis factor-α was not. In conclusion, energy expenditure significantly correlated with disease activity in UC patients but not in CD patients. These results indicate that establishing daily energy requirements based on disease activity of UC is imperative for improving the nutritional status of patients.

Changes in energy metabolism after induction therapy in patients with severe or moderate ulcerative colitis.

We investigated the changes in energy expenditure during induction therapy in patients with severe or moderate ulcerative colitis. Thirteen patients (10 men, 3 women; mean age, 36.5 years) with ulcerative colitis admitted to the Shiga University Hospital were enrolled in this study. We measured the resting energy expenditure and respiratory quotients of these patients before and after induction therapy with indirect calorimetry. We analyzed the changes of nutritional status and serum inflammatory cytokine levels and also evaluated the relationship between energy metabolism and disease activity by using the Seo index and Lichtiger index. The resting energy expenditure was 26.3 ± 3.8 kcal/kg/day in the active stage and significantly decreased to 23.5 ± 2.4 kcal/kg/day after induction therapy (p<0.01). The resting energy expenditure changed in parallel with the disease activity index and C-reactive protein and inflammatory cytokine levels. The respiratory quotient significantly increased after induction therapy. Thus, moderate to severe ulcerative colitis patients had a hyper-metabolic status, and the energy metabolism of these patients significantly changed after induction therapy. Therefore, we recommend that nutritional management with 30-34 kcal/kg/day (calculated as measured resting energy expenditure × activity factor, 1.3) may be optimal for hospitalized ulcerative colitis patients.

A current life table and causes of death for insured dogs in Japan.

The life expectancies and causes of death were evaluated in 299,555 dogs insured in Japan between 1 April 2010 and 31 March 2011, of which 4169 dogs died during this period. The overall life expectancy of dogs was 13.7 years. The probability of death was high in the first year of life, lowest in the second and third years, and increased exponentially after 3 years of age. The life expectancy was 13.8 years in the <5 kg body weight group, 14.2 years in the 5-10 kg body weight group, 13.6 years in the 10-20 kg body weight group, 12.5 years in the 20-40 kg body weight group and 10.6 years in the ≥40 kg body weight group. As body weight increases, life expectancy tended to decrease except in the <5 kg body weight group. The probability of death increased as dogs got older for most potential causes of death. Neoplasia resulted in the highest probability of death, especially in the large and giant breed groups. Cardiovascular system disorders were the second major cause of death and the toy group had a probability of death significantly higher than the other breed groups at age 12+.

Breed, gender and age pattern of diagnosis for veterinary care in insured dogs in Japan during fiscal year 2010.

We calculated the annual prevalence of diseases of 18 diagnostic categories in the insured dog population in Japan, using data from 299,555 dogs insured between April 2010 and March 2011. The prevalence was highest for dermatological disorders (22.6% for females and 23.3% for males), followed by otic diseases (16.4% for females and 17.2% for males) and digestive system disorders (15.7% for females and 16.4% for males). The prevalence of cardiovascular, urinary, neoplasia and endocrine disorders, increased with age; infectious diseases and injuries showed a high prevalence at young ages, and the prevalence of musculoskeletal and respiratory disorders showed a bimodal peak at young and old ages. A large variation in prevalence was observed between breeds for dermatological, otic, digestive, ophthalmological and cardiovascular disorders.

A revised method for determination of dialkylphosphate levels in human urine by solid-phase extraction and liquid chromatography with tandem mass spectrometry: application to human urine samples from Japanese children.

OBJECTIVES: Biological monitoring of organophosphorus insecticide (OP) metabolites, specifically dialkylphosphates (DAP) in urine, plays a key role in low-level exposure assessment of OP in individuals. The aims of this study are to develop a simple and sensitive method for determining four urinary DAPs using high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS), and to assess the concentration range of urinary DAP in Japanese children. METHODS: Deuterium-labeled DAPs were used as internal standards. Urinary dimethylphosphate (DMP) and diethylphosphate (DEP), which passed through the solid-phase extraction (SPE) column, and dimethylthiophosphate (DMTP) and diethylthiophosphate (DETP), which were extracted from a SPE column using 2.5 % NH3 water including 50 % acetonitrile, were prepared for separation analysis. The samples were then injected into LC-MS/MS. The optimized method was applied to spot urine samples from 3-year-old children (109 males and 116 females) living in Aichi Prefecture in Japan. RESULTS: Results from the validation study demonstrated good within- and between-run precisions (<10.7 %) with low detection limits (0.4 for DMP and DMTP, 0.2 for DEP and 0.1 µg/L for DETP). The geometric mean values and detection rates of the urinary DAPs in Japanese children were 14.4 µg/L and 100 % for DMP, 5.3 µg/L and 98 % for DMTP, 5.5 µg/L and 99 % for DEP, and 0.6 µg/L and 80 % for DETP, respectively. CONCLUSIONS: The present high-throughput method is simple and reliable, and can thereby further contribute to development of an exposure assessment of OP. The present study is the first to reveal the DAP concentrations in young Japanese children.