Associations between information and communication technology use and frailty in community-dwelling old-old adults: results from the ILSA-J.

OBJECTIVES: Frailty is a significant cause of adverse health events including long-term care and hospitalization. Although information and communication technology (ICT) has become an integral part of modern life, it remains unclear whether ICT use is associated with frailty. DESIGN: A cross-sectional study (Integrated Longitudinal Studies on Aging in Japan, ILSA-J). SETTING AND PARTICIPANTS: Aged 75 and older data from the ILSA-J in 2017 (n = 2893). METHODS: ICT use was measured using the technology usage sub-items of the Japan Science and Technology Agency Index of Competence. Specifically, the use of mobile phones, ATMs, DVD players, and sending e-mails were rated as "yes" (able to do) or "no" (unable to do), with the first quintile (≤1 point) defined as ICT non-users. Frailty was assessed using the Japanese version of the Cardiovascular Health Study criteria based on the phenotype model (e.g., weight loss, slowness, weakness, exhaustion, and low activity). Further, multivariate logistic regression analysis analyzed its association with ICT use. Subgroup analyses were stratified according to gender, years of education, and living arrangements. RESULTS: Higher ICT use was not associated with frailty after adjusting for covariates (odds ratio [OR]: 0.53; 95%CI 0.39-0.73). Similar associations were found in the sub-groups of women (OR 0.45, 95%CI 0.30-0.66), <13 years of education (OR 0.48, 95%CI 0.34-0.67), living alone (OR 0.46, 95%CI 0.27-0.79), and living together (OR 0.57, 95%CI 0.38-0.85). No association existed between using ICT and frailty in the sub-groups of men and ≥13 years of education. CONCLUSIONS AND IMPLICATIONS: Higher ICT use is associated with the absence of frailty in individuals 75 years and older. Such benefits may be particularly pronounced in women, those with lower levels of education, and older adults living alone or with others.

Ubiquitin-specific protease 7 inhibitors reveal a differentiated mechanism of p53-driven anti-cancer activity.

The USP7 deubiquitinase regulates proteins involved in the cell cycle, DNA repair, and epigenetics and has been implicated in cancer progression. USP7 inhibition has been pursued for the development of anti-cancer therapies. Here, we describe the discovery of potent and specific USP7 inhibitors exemplified by FX1-5303. FX1-5303 was used as a chemical probe to study the USP7-mediated regulation of p53 signaling in cells. It demonstrates mechanistic differences compared to MDM2 antagonists, a related class of anti-tumor agents that act along the same pathway. FX1-5303 synergizes with the clinically approved BCL2 inhibitor venetoclax in acute myeloid leukemia (AML) cell lines and ex vivo patient samples and leads to strong tumor growth inhibition in in vivo mouse xenograft models of multiple myeloma and AML. This work introduces new USP7 inhibitors, differentiates their mechanism of action from MDM2 inhibition, and identifies specific opportunities for their use in the treatment of AML.

Development and Validation of the Meiji Nutritional Profiling System (Meiji NPS) to Address Dietary Needs of Adults and Older Adults in Japan.

This study introduces the Meiji Nutritional Profiling System (Meiji NPS), which was specifically designed to respond to age-related shifts in nutrient requirements among Japanese adults (<65 years old) and older adults (≥65 years old). Japan has one of the most aged societies in the world. The health issues of interest are malnutrition and lifestyle-related diseases among adults and frailty among older adults. Two versions of the NPS were developed based on nutrients to encourage (protein, dietary fibers, calcium, iron, and vitamin D), food groups to encourage (fruits, vegetables, nuts, legumes, and dairy), and nutrients to limit (energy, saturated fatty acids, sugars, and salt equivalents). The Meiji NPS for older adults did not include iron or saturated fatty acids. The algorithms were based on the Nutrient-Rich Foods Index (NRF). The convergent validity between the Meiji NPS and the existing NPSs for the same foods was confirmed using Spearman's correlation coefficients (NRF: r = 0.67 for adults and r = 0.60 for older adults; Health Star Rating: r = 0.64 for adults and r = 0.61 for older adults). The Meiji NPS may be useful for nutritional evaluation and reformulation of food products, tailored to adults and older adults to ameliorate health issues in Japan.

Evolutionary dependence of host type and chasmothecial appendage morphology in obligate plant parasites belonging to Erysipheae (powdery mildew, Erysiphaceae).

Evolutionary relationships between the morphological and ecological traits of fungi are poorly understood. The appendages of chasmothecia, which are sexual reproductive organs of Erysiphaceae, are considered to play a crucial role in the overwintering strategies of these fungi on host plants. Previous studies suggested that both the host type and appendage morphology evolved at the same nodes and transitioned from complex appendages on deciduous hosts to simple appendages on herb/evergreen hosts. However, the evolutionary dependence between host type and appendage morphology remains unproven owing to the limited species data used in analyses. To elucidate the evolutionary relationship between host type and appendage morphology, we used phylogenetic comparative methods (PCMs) to investigate the state transition, ancestral state, evolutionary dependence, and contingent evolution within Erysipheae, the largest and most diverse tribe in Erysiphaceae. Our PCMs, based on a comprehensive data set of Erysipheae, revealed that the most ancestral states were deciduous host types and complex appendages. From these ancestral states, convergent evolution toward the herb/evergreen host types and simple appendages occurred multiple times at the same nodes. For the first time in Erysiphaceae, we detected an evolutionary dependence between host type and appendage morphology. This is one of the few examples in which evolutionary dependence between host phenology and morphological traits in plant-parasitic fungi was demonstrated using PCMs. Appendage simplification on herb/evergreen hosts and complications on deciduous hosts can be reasonably explained by the functional advantages of each appendage type in different overwintering strategies. These expected appendage functions can explain approximately 90% of host type and appendage morphology combinations observed in the analyzed taxa. However, our results also highlighted the occurrence of evolutionary shifts that deviate from the expected advantages of each appendage morphology. These seemingly irrational shifts might be interpretable from the flexibility of overwintering strategies and quantification of appendage functions.

Higher-level competence: Results from the Integrated Longitudinal Studies on Aging in Japan (ILSA-J) on the shape of associations with impaired physical and cognitive functions.

AIM: This study aimed to examine the relationships between levels of competence and impaired physical and cognitive functions in older adults. METHODS: We used a data set of the Integrated Longitudinal Studies on Aging in Japan for 2017 including 5475 community-dwelling older adults. Levels of competence were assessed using the Japan Science and Technology Agency Index of Competence (JST-IC). Grip strength (low grip strength: <28 kg for men and <18 kg for women) and gait speed (slow gait speed: <1.0 m/s for both sexes) were evaluated as physical function measurements, and the Mini-Mental State Examination (cognitive decline: <24 on the Mini-Mental State Examination) was used to assess cognitive function. RESULTS: The JST-IC had areas under the curve estimated from receiver operating characteristic analysis ranging from 0.65 to 0.73 for detecting low function as assessed by these tests. Restricted cubic spline curves showed that the shape of the association between the JST-IC and impaired function depended on sex and the test used. The comparison between perfect and imperfect JST-IC scores showed significant differences in the prevalence of low grip strength in both sexes, slow gait speed in women, and cognitive decline in men. CONCLUSIONS: It may be insufficient to identify those with impaired physical or cognitive function using the JST-IC. The shape of the association with the JST-IC varies across their measurements. Our findings can help interpret JST-IC scores in the context of low physical and cognitive functions. Geriatr Gerontol Int 2024; 24: 352-358.

Inverse Association between Cheese Consumption and Lower Cognitive Function in Japanese Community-Dwelling Older Adults Based on a Cross-Sectional Study.

Diet modification may contribute to the prevention of age-related cognitive decline. The association between dairy product consumption and cognitive function in older people remains unknown. We investigated whether cheese intake is associated with lower cognitive function (LCF) in community-dwelling older adults. This cross-sectional study included 1503 adults aged over 65 years. The analyzed data were obtained through face-to-face interviews and functional ability measurement. Cognitive function was assessed using the mini-mental state examination (MMSE), and a score ≤23 was defined as LCF. The prevalence of LCF was 4.6%, and this group had smaller calf circumference, slower usual walking speed, and a more frequent history of anemia than subjects with MMSE scores >23. After adjusting for confounding factors, logistic regression analysis revealed cheese intake (odds ratio (OR) = 0.404, 95% confidence interval (CI) = 0.198-0.824), age (OR = 1.170, 95% CI = 1.089-1.256), usual walking speed (OR = 0.171, 95% CI = 0.062-0.472) and calf circumference (OR = 0.823, 95% CI = 0.747-0.908) to be significant factors associated with LCF. Although the present study was an analysis of cross-sectional data of Japanese community-dwelling older adults, the results suggest that cheese intake is inversely associated with LCF.

Effects of Daily Consumption of Soy Products on Basic/Instrumental Activities of Daily Living in Community-Dwelling Japanese Women Aged 75 Years and Older: A 4-Year Cohort Study.

Introduction: Since soy isoflavones compensate for age-related estrogen reduction, adequate intake of soy products may prevent the decline in activities of daily living (ADL) due to estrogen reduction in women. However, it is unclear whether regular soy product intake prevents ADL decline. This study examined the effects of soy product consumption on basic/instrumental ADL (BADL/IADL) in Japanese women 75 years or older for 4 years. Materials and Methods: The subject population consisted of 1289 women aged 75 years or older living in Tokyo who underwent private health examinations in 2008. For 1114 (or 1042) participants without baseline BADL (or IADL) disability, we examined the association between baseline soy product consumption frequency and the BADL (or IADL) disabilities 4 years later using logistic regression analyses. The models were adjusted for baseline age, or further for dietary variety for food groups other than soy products, exercise and sport participation, smoking, pre-existing disease number, and body mass index. Results: Regardless of adjustment for potential confounding factors, less frequent soy product consumption was associated with higher BADL or IADL disability incidence. In the fully adjusted models, the trend toward a higher incidence of disabilities with less frequent soy product consumption was statistically significant for both BADL (p = 0.001) and IADL (p = 0.007). Conclusions: Those who consumed soy products more frequently at baseline were less likely to develop BADL and IADL disabilities after 4 years than those who did not. The results show that daily soy product consumption may prevent functional ADL decline in older Japanese women.

Sensitive and specific quantification of antisense oligonucleotides using probe alteration-linked self-assembly reaction technology.

Quantitative bioanalysis is essential when establishing pharmacokinetic properties during the drug development process. To overcome challenges of sensitivity, specificity and process complexity associated with the conventional analysis of antisense oligonucleotides (ASOs), a new approach to nonenzymatic hybridization assays using probe alteration-linked self-assembly reaction (PALSAR) technology as a signal amplifier was evaluated. PALSAR quantification of ASOs in mouse tissue and plasma was able to achieve a high sensitivity ranging from 1.5 to 6 pg/ml, intra-/interday accuracies in the range of 86.8-119.1% and 88.1-113.1%, respectively, and precision of ≤17.2%. Furthermore, crossreactivity of 3'n-1, a metabolite with a single base difference, was <1%. Our approach provides an auspicious method for distinguishing metabolites and detecting ASOs with high sensitivity and specificity.

Prognosis of home-cared or hospital-treated acute fever in older adults: A prospective multicenter case-control study.

AIMS: This study aimed to investigate the differences in the prognosis of older patients who received home care or hospitalized care to treat acute fever in Japan. METHODS: This prospective case-control study screened 192 registered acutely pyrexic older patients who received home care at 10 medical institutions in Japan, and enrolled 15 and 30 patients who were treated in the hospital (hospitalized group) and at home (home-care group), respectively, matched for fever and the physical conditions before fever onset. Intergroup differences in the 90-day mortality from fever onset and changes in patients' disability and dementia from the pre-fever to 90 days post-fever onset were determined. RESULTS: No significant intergroup difference in the 90-day mortality rate was detected (26.7% vs 13.3% for hospitalized and home-care groups, respectively, P = 0.41). Disability tended to worsen in the hospitalized group compared with the home-care group (54.5% vs 23.1%, respectively, P = 0.06), whereas dementia significantly worsened in the hospitalized group compared with the home-care group (45.5% vs 3.8%, respectively, P = 0.02). CONCLUSIONS: Home care confers a better prognosis for treating acute fever in older people whose daily functions have deteriorated enough to necessitate regular home care. This study assists those people in making informed choices about where to receive treatment for acute fever. Geriatr Gerontol Int 2023; 23: 355-361.

Impact of osteosarcopenia on disability and mortality among Japanese older adults.

BACKGROUND: In clinical settings, muscle mass and bone mineral density assessments are usually performed using dual-energy X-ray absorptiometry (DXA), the clinical standard technique. However, DXA is often unavailable in community settings. This study aimed to determine whether osteoporosis, osteopenia (OP) and sarcopenia (SP) identified by simplified instruments are associated with the future incidence of disability and mortality and evaluate the validity of these instruments as community screening tools. We also examined osteosarcopenia (OS), defined as the coexistence of OP and SP, as a new indicator of geriatric syndromes to determine whether it has an additive effect on adverse outcome incidence compared with OP and SP alone. METHODS: In total, 8995 older adults participated in the study (women: 51.7%, average age: 73.5 ± 5.4 years). Data were extracted from the Japanese national cohort study, National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. We determined OP based on T-scores generated based on the speed of sound, which is the time taken for ultrasound waves to go through a determined distance in the calcaneus bone. Skeletal muscle mass was evaluated using a bioimpedance analysis device. Handgrip strength and walking speed were measured as physical performance indicators. Incidences of disability and mortality were prospectively determined for 5 years. RESULTS: The prevalence of OP, SP and OS was 45.5%, 3.9% and 7.4%, respectively. The incidence of disability in the nonOP/nonSP, OP, SP and OS groups was 6.5%, 14.9%, 20.5% and 33.5%, respectively. The incidence of mortality in the nonOP/nonSP, OP, SP and OS groups was 4.0%, 4.9%, 10.3% and 10.2%, respectively. Participants with OP (hazard ratio [HR]: 1.45, 95% confidence interval [CI]: 1.25-1.68), SP (HR: 1.38, 95% CI: 1.08-1.76) and OS (HR: 1.73, 95% CI: 1.43-2.09) had a higher risk of disability than nonOP/nonSP participants. Participants with OP (HR: 1.31, 95% CI: 1.04-1.64) and OS (HR: 1.45, 95% CI: 1.05-2.00) had a higher risk of mortality than nonOP/nonSP participants. SP was not significantly related to mortality (HR: 1.14, 95% CI: 0.90-1.45). There was no statistical interaction between OP and SP in incident disability and mortality. CONCLUSIONS: Among older adults, OS identified by bioimpedance and quantitative ultrasound assessments was associated with an increased risk of disability and mortality. Further research is needed to implement these findings in community health activities, such as setting precise cut-off values and constructing accurate disability and mortality prediction models.

A non-pharmacological multidomain intervention of dual-task exercise and social activity affects the cognitive function in community-dwelling older adults with mild to moderate cognitive decline: A randomized controlled trial.

The present study aimed to determine the impact of a 10-month multidomain program using dual-task exercise and social activity conducted at a community-based facility on improved cognitive function in older adults with mild to moderate cognitive decline. The participants included 280 community-dwelling older adults (age 71-91 years) with mild to moderate cognitive decline. The intervention group exercised for 90 min/day, once a week. Their routine included aerobic exercise and dual-task training which cognitive tasks were performed in combination with exercise. The control group attended health education classes thrice. Before and after the intervention, we measured their cognitive function, physical function, daily conversation, and physical activity. The mean adherence rate of the intervention class was 83.0%. According to a repeated-measures multivariate analysis of covariance in an intent-to-treat analysis, logical memory and 6-min walking distance demonstrated a significant time and group interaction effect. Regarding daily physical activities, we observed significant differences in the daily step count and moderate-to-vigorous physical activity in the intervention group. Our non-pharmacological multidomain intervention resulted in a modest improvement in the cognitive or physical function and building health behavior. It may be a helpful program with a potential role in preventing dementia. Clinical Trial Registration: http://clinicaltrials.gov Identifier ID: UMIN000013097.

Lifestyle Evolution Analysis by Binary-State Speciation and Extinction (BiSSE) Model.

Phylogenetic comparative methods (PCMs) combine statistics and evolutionary models to infer the dynamics of trait evolution and diversification that underlie the observed phylogeny. While PCMs have been used to study macro-evolutionary processes and evolutionary transitions of macroorganisms, their application to microbes is still limited. With the abundance of publicly available genomic and trait character data for diverse microbes nowadays, applications of PCMs on these data can provide insights into the fundamental principles that govern microbial evolution. Here, we introduce the Binary-State Speciation and Extinction (BiSSE) model, which is a relatively simple yet powerful approach for analyzing trait evolution. We begin by explaining the theoretical background and intuition behind the BiSSE model. Then, R commands for running the BiSSE model are presented. Finally, we introduce a case study that successfully applied the BiSSE model to investigate generalist and specialist microbial lifestyle evolution.

Association between Neutrophil-to-Lymphocyte Ratio and Physical Function in Older Adults: A Community-Based Cross-Sectional Study in Japan.

Inflammatory responses contribute to physical decline in older adults. Clinical studies have shown that the neutrophil-to-lymphocyte ratio (NLR), a marker of inflammation, is associated with physical decline. However, its association with physical function in community-dwelling older people is still unclear. Hence, we used cross-sectional data to investigate the relationship between NLR and physical function in community-dwelling older adults. Specifically, we analyzed data corresponding to 818 individuals (336 men and 482 women) aged ≥ 75 years, all of whom participated in comprehensive health examinations, including face-to-face interviews, biochemical analyses, and physical function tests. Using these data, we performed multivariable logistic regression analysis to assess the relationship between NLR and physical function, adjusting for sex, age, education, alcohol consumption, smoking, instrumental activity of daily living, body mass index, chronic disease, physical activity, serum albumin level, and depressive mood. The results showed that a higher NLR was associated with a lower grip strength, lower knee extension strength, and slower walking speed. Importantly, the relationship between NLR and physical function was maintained after adjusting for the confounding factors. Thus, we showed a significant association between NLR and physical function, supporting the use of NLR as a marker of physical function in community-dwelling older adults.

Phenotypic systems biology for organisms: Concepts, methods and case studies.

Design principles of phenotypes in organisms are fundamental issues in physical biology. So far, understanding "systems" of living organisms have been chiefly promoted by understanding the underlying biomolecules such as genes and proteins, and their intra- and inter-relationships and regulations. After a long period of sophistication, biophysics and molecular biology have established a general framework for understanding 'molecular systems' in organisms without regard to species, so that the findings of fly studies can be applied to mouse studies. However, little attention has been paid to exploring "phenotypic systems" in organisms, and thus its general framework remains poorly understood. Here I review concepts, methods, and case studies using butterfly and moth wing patterns to explore phenotypes as systems. First, I present a unifying framework for phenotypic traits as systems, termed multi-component systems. Second, I describe how to define components of phenotypic systems, and also show how to quantify interactions among phenotypic parts. Subsequently, I introduce the concept of the macro-evolutionary process, which illustrates how to generate complex traits. In this point, I also introduce mathematical methods, "phylogenetic comparative methods", which provide stochastic processes along molecular phylogeny as bifurcated paths to quantify trait evolution. Finally, I would like to propose two key concepts, macro-evolutionary pathways and genotype-phenotype loop (GP loop), which must be needed for the next directions. I hope these efforts on phenotypic biology will become one major target in biophysics and create the next generations of textbooks. This review article is an extended version of the Japanese article, Biological Physics in Phenotypic Systems of Living Organisms, published in SEIBUTSU-BUTSURI Vol. 61, p. 31-35 (2021).

Temporal trends in cognitive function among community-dwelling older adults in Japan: Findings from the ILSA-J integrated cohort study.

BACKGROUND: As the population ages, it is important to consider whether older adults tend to have healthier lives. This study examined temporal trends in cognitive function among community-dwelling Japanese older adults. METHODS: The data source for this study was Integrated Longitudinal Studies on Aging in Japan (ILSA-J). We collected representative values for the Mini-Mental State Examination (MMSE) score obtained in 2010 and 2017; mean, standard deviation, and prevalence of ≤23 as cognitive impairment and ≥28 as intact cognitive function. Six cohorts (n=8,575) in 2010 and seven cohorts (n=6,089) in 2017 were included (age range 65-89). One-group meta-analyses were conducted to calculate pooled means of MMSE scores, the pooled prevalence of MMSE scores ≤23 and ≥28, and 95% confidence intervals (CIs). RESULTS: The mean MMSE score was higher in 2017 than in 2010 for all age groups in both men and women. The prevalence of MMSE ≤23 was lower in 2017 than in 2010 for all age groups for men and was lower in 2017 than in 2010 for all age groups other than for women aged 75-79 years. The prevalence of MMSE ≥28 was higher in 2017 than in 2010 for all age groups in both men and women. In addition, the pooled means of years of education was lower in 2010 than in 2017, which might be an explanatory factor. CONCLUSIONS: This study suggests that the cognitive function of community-dwelling Japanese older adults has improved in recent years. Future studies need to identify factors associated with the improvement.

What Should Be Considered When Evaluating the Quality of Home Care? A Survey of Expert Opinions on the Evaluation of the Quality of Home Care in Japan.

Intending to obtain scientific evidence to use in developing indicators for evaluating the quality of home care, we surveyed doctors, nurses, and other home care professionals to determine the points they consider to be essential in evaluating home care. We investigated all 901 clinics registered to the National Association of Medical Institutions Supporting Home Care and a random sample of 600 Visiting Nurse Service stations registered to the National Association for Visiting Nurse Service in Japan. A total of 539 questionnaire responses were received (response rate: 35.9%). In this study, a factor analysis revealed four factors to be considered when evaluating the quality of home care: (1) patients' and family members' level of satisfaction, (2) home care process, (3) structure of home care, and (4) medical outcomes. The factor of the satisfaction of patients and family members identified in the present study was not considered in previous studies for evaluating the quality of care in Japan. Satisfaction is the point of difference in goals between hospital-based care and home care, and it requires different measurement indicators. Home care professionals expect to help relieve the physical and psychological burden felt by the patient and their family. Thus, on the evaluation indicators of quality of home care, their perspectives from the present study are valuable.

The Association of Sleep Habits and Advancing Age in Japanese Older Adults: Results from the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes.

BACKGROUND: The association of sleep habits with "advancing age among older adults" is not fully understood. OBJECTIVES: The purpose of the present study was to examine the association of sleep habits with advancing age among community-dwelling older adults in Japan. METHODS: A total of 18,005 older people (mean age: 73.2 ± 6.0 years; 8,070 men and 9,935 women) from the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes were analyzed. Participants were asked in face-to-face interviews about the times they usually go to bed, fall asleep, wake-up, and get up. The amount of time spent in bed and self-reported sleep duration were then calculated from the differences between these times. As other parameters, the subjects were also asked about sleep latency, time spent in bed after waking up, number of nocturnal awakenings, and duration of napping in a typical day. RESULTS: The results of the Jonckheere-Terpstra test showed that all sleep parameters shifted to an earlier time (going to bed, falling asleep, waking up, and getting out of bed), longer duration (sleep duration, time spent in bed, sleep latency, time spent in bed after waking up, and napping), or more nocturnal awakenings with advancing age (all p < 0.01). Among the men, the time of waking up was not significantly associated with age, while among the women, the time of getting up was not significantly associated with age. CONCLUSION: These results from a large cohort show the age-related trends of sleep habits in community-dwelling older adults in Japan. Our results revealed that a longer duration and earlier timing of sleep are associated with advancing age.

Evolutionary patterns of host type and chasmothecial appendage morphology in obligate plant parasites belonging to Cystotheceae (powdery mildew, Erysiphaceae).

The chasmothecial appendages of Erysiphaceae are considered to function in the overwintering strategy and evolve morphologically in line with transitions of different host type. However, the evolutionary patterns and relationships of these traits have not yet been verified using statistical models based on phylogenetic information. We aimed to clarify the evolutionary process of host type and appendage morphology in Cystotheceae using phylogenetic comparative methods (PCMs) and to evaluate the evolutionary relationship of these traits. The ancestral state estimation of host types showed that the deciduous type is the most ancestral in Cystotheceae, and the herb or evergreen types evolved secondarily four times and twice, respectively. Branched- or circinate-type appendages were estimated to be the most ancestral, and the mycelioid and rudimentary types evolved secondarily thrice and once, respectively. The results of the random forest analysis showed that the host type was predictable from the phylogeny and appendage morphology. The ancestral state estimation suggested that simultaneous transitions of the host type and appendage morphology occurred at several ancestral nodes. These results suggest some functional relationships between host type and appendage morphology, but there was no statistical support for an overall trend in evolutionary dependence between these traits. Our results demonstrate the utility of PCMs in the study of trait evolution in Cystotheceae, which can be applied to a broader phylogeny of powdery mildews to elucidate the evolutionary relationship and functional causality of phenotypic traits.

Effect of enterally administered sleep-promoting medication on the intravenous sedative dose and its safety and cost profile in mechanically ventilated patients: A retrospective cohort study.

BACKGROUND: The clinical effect of enteral administration of sleep-promoting medication (SPM) in mechanically ventilated patients remains unclear. This study aimed to investigate the relationship between enteral SPM administration and the intravenous sedative dose and examine the safety and cost of enteral SPM administration. METHODS: This single-center retrospective cohort study was conducted in a Japanese tertiary hospital intensive care unit (ICU). The exposure was enteral SPM administration during mechanical ventilation. The outcome was the average daily propofol dose per body weight administered as a continuous sedative during mechanical ventilation. Patients were divided into three groups based on the timing of SPM administration at ICU admission: "administration within 48 hours (early administration [EA])," "administration after 48 hours (late administration [LA])," and "no administration (NA)." We used multiple linear regression models. RESULTS: Of 123 included patients, 37, 50, and 36 patients were assigned to the EA, LA, and NA groups, respectively. The average daily propofol dose per body weight was significantly lower in the EA group than in the LA and NA groups (ß -5.13 [95% confidence interval (CI) -8.93 to -1.33] and ß -4.51 [95% CI -8.59 to -0.43], respectively). Regarding safety, enteral SPM administration did not increase adverse events, including self-extubation. The total cost of neuroactive drugs tended to be lower in the EA group than in the LA and NA groups. CONCLUSIONS: Early enteral SPM administration reduced the average daily propofol dose per body weight without increasing adverse events.

A cross-population atlas of genetic associations for 220 human phenotypes.

Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (ntotal = 628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wide summary statistics, and identified latent genetic components, which pinpointed responsible variants and biological mechanisms underlying current disease classifications across populations. The decomposed components enabled genetically informed subtyping of similar diseases (for example, allergic diseases). Our study suggests a potential avenue for hypothesis-free re-investigation of human diseases through genetics.