ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline.

H3K9 trimethylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2). We show that in male meiosis, ATF7IP2 amasses on autosomal and X-pericentric heterochromatin, spreads through the entirety of the sex chromosomes, and accumulates on thousands of autosomal promoters and retrotransposon loci. On the sex chromosomes, which undergo meiotic sex chromosome inactivation (MSCI), the DNA damage response pathway recruits ATF7IP2 to X-pericentric heterochromatin, where it facilitates the recruitment of SETDB1, a histone methyltransferase that catalyzes H3K9me3. In the absence of ATF7IP2, male germ cells are arrested in meiotic prophase I. Analyses of ATF7IP2-deficient meiosis reveal the protein's essential roles in the maintenance of MSCI, suppression of retrotransposons, and global up-regulation of autosomal genes. We propose that ATF7IP2 is a downstream effector of the DDR pathway in meiosis that coordinates the organization of heterochromatin and gene regulation through the spatial regulation of SETDB1-mediated H3K9me3 deposition.

A wireless, implantable bioelectronic system for monitoring urinary bladder function following surgical recovery.

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.

Transcript Profiles of Microglia/Macrophage Cells at the Borders of Chronic Active and Subpial Gray Matter Lesions in Multiple Sclerosis.

OBJECTIVE: Microglia/macrophages line the border of demyelinated lesions in both cerebral white matter and the cortex in the brains of multiple sclerosis patients. Microglia/macrophages associated with chronic white matter lesions are thought to be responsible for slow lesion expansion and disability progression in progressive multiple sclerosis, whereas those lining gray matter lesions are less studied. Profiling these microglia/macrophages could help to focus therapies on genes or pathways specific to lesion expansion and disease progression. METHODS: We compared the morphology and transcript profiles of microglia/macrophages associated with borders of white matter (WM line) and subpial gray matter lesions (GM line) using laser capture microscopy. We performed RNA sequencing on isolated cells followed by immunocytochemistry to determine the distribution of translational products of transcripts increased in WM line microglia. RESULTS: Cells in the WM line appear activated, with shorter processes and larger cell bodies, whereas those in the GM line appear more homeostatic, with smaller cell bodies and multiple thin processes. Transcript profiling revealed 176 genes in WM lines and 111 genes in GM lines as differentially expressed. Transcripts associated with immune activation and iron homeostasis were increased in WM line microglia, whereas genes belonging to the canonical Wnt signaling pathway were increased in GM line microglia. INTERPRETATION: We propose that the mechanisms of demyelination and dynamics of lesion expansion are responsible for differential transcript expression in WM lines and GM lines, and posit that increased expression of the Fc epsilon receptor, spleen tyrosine kinase, and Bruton's tyrosine kinase, play a key role in regulating microglia/macrophage function at the border of chronic active white matter lesions. ANN NEUROL 2024;95:907-916.

Liebig's law of the minimum in the TGF-ß/SMAD pathway.

Cells use signaling pathways to sense and respond to their environments. The transforming growth factor-ß (TGF-ß) pathway produces context-specific responses. Here, we combined modeling and experimental analysis to study the dependence of the output of the TGF-ß pathway on the abundance of signaling molecules in the pathway. We showed that the TGF-ß pathway processes the variation of TGF-ß receptor abundance using Liebig's law of the minimum, meaning that the output-modifying factor is the signaling protein that is most limited, to determine signaling responses across cell types and in single cells. We found that the abundance of either the type I (TGFBR1) or type II (TGFBR2) TGF-ß receptor determined the responses of cancer cell lines, such that the receptor with relatively low abundance dictates the response. Furthermore, nuclear SMAD2 signaling correlated with the abundance of TGF-ß receptor in single cells depending on the relative expression levels of TGFBR1 and TGFBR2. A similar control principle could govern the heterogeneity of signaling responses in other signaling pathways.

iRhom2 deficiency reduces sepsis-induced mortality associated with the attenuation of lung macrophages in mice.

Sepsis has a high mortality rate and leads to multi-organ failure, including lung injury. Inactive rhomboid protease family protein (iRhom2) has been identified as accountable for the release of TNF-α, a crucial mediator in the development of sepsis. This study aimed to evaluate the role of iRhom2 in sepsis and sepsis-induced acute lung injury (ALI). TNF-α and IL-6 secretion in vitro by peritoneal macrophages from wild-type (WT) and iRhom2 knoukout (KO) mice was assessed by enzyme-linked immunosorbent assay. Cecal ligation and puncture (CLP)-induced murine sepsis model was used for in vivo experiments. To evaluate the role of iRhom2 deficiency on survival during sepsis, both WT and iRhom2 KO mice were monitored for 8 consecutive days following the CLP. For histologic and biochemical examination, the mice were killed 18 h after CLP. iRhom2 deficiency improved the survival of mice after CLP. iRhom2 deficiency decreased CD68+ macrophage infiltration in lung tissues. Multiplex immunohistochemistry revealed that the proportion of Ki-67+ CD68+ macrophages was significantly lower in iRhom2 KO mice than that in WT mice after CLP. Moreover, CLP-induced release of TNF-α and IL-6 in the serum were significantly inhibited by iRhom2 deficiency. iRhom2 deficiency reduced NF-kB p65 and IκBα phosphorylation after CLP. iRhom2 deficiency reduces sepsis-related mortality associated with attenuated macrophage infiltration and proliferation in early lung injury. iRhom2 may play a pivotal role in the pathogenesis of sepsis and early stage of sepsis-induced ALI. Thus, iRhom2 may be a potential therapeutic target for the management of sepsis and sepsis-induced ALI.

TEK gene-related primary congenital glaucoma: Phenotypic features and mutational spectrum in a Mexican cohort of 10 unrelated families.

Primary congenital glaucoma (PCG) is one of the leading causes of visual damage and blindness, severely affecting the quality of life of affected children. It is characterized by cupping of the optic disc and loss of ganglion cells due to elevated intraocular pressure. While most PCG patients exhibit epiphora, photophobia, and buphthalmos with corneal opacity, variability in phenotypic manifestations is not uncommon. Prompt diagnosis and treatment of PCG affected individuals becomes relevant to preserve visual function throughout their lives. Most PCG cases are sporadic or autosomal recessive; however, an incompletely dominant autosomal dominant form arising from mutations in the TEK gene has recently been demonstrated. Here, we describe the clinical and mutational features of a cohort of Mexican patients with TEK-related PCG. Our results support the involvement of the TEK gene as an important cause of the disease in our ethnic group and expand the mutational spectrum causing PCG by reporting 10 novel disease-causing variants.

Six-year trend of subsequent allergic diseases following Kawasaki disease and its clinical implications: A population-based matched cohort study of 34,712 patients.

BACKGROUND: It has been suggested that allergic diseases may increase after Kawasaki disease (KD). We aimed to analyze the temporal patterns of allergic disease incidence after KD. METHODS: A nationwide population-based matched cohort study was conducted using data from the Korean National Health Insurance claims database. Patients aged <5 years diagnosed with KD and their 1:3 propensity score-matched controls were included. Three cohorts were established: Cohort A, patients with allergies; Cohort B, patients without allergies; and Cohort C, patients without allergies, but excluding patients with birth history and underlying medical conditions. Cumulative incidence rates (%) and associated hospital visits for allergic rhinitis, atopic dermatitis, urticaria, and asthma were compared between the cases and controls during the 6-year follow-up period. RESULTS: The study population comprised 8678 patients diagnosed with KD and 26,034 controls. In Cohort A, although initially, there were intergroup differences in the number of hospital visits for certain allergic diseases, these differences were inconsistent and varied depending on the type of allergic disease. Over time, the differences narrowed, and by the sixth year, the gap had decreased significantly. In Cohorts B and C, the initial incidence rates of the four allergic diseases and associated hospital visits were lower in patients with KD as compared to controls. However, with a faster rate of increase, the incidence rates and number of hospital visits eventually surpassed those of the controls. CONCLUSIONS: The pattern of delayed increase in cumulative incidence rates and hospital visits for allergic diseases after KD suggests the possibility of a shared genetic or immunologic susceptibility between KD and allergic diseases, which becomes evident over time, rather than a direct influence of KD resulting in allergic diseases.

Establishing Conditions for Blood Smear Drying and Staining on Sysmex SP-50 for Leukocyte Differential Count.

BACKGROUND: The purpose of this study was to determine the staining conditions and appropriate fan1 start time (FAN1ST) for Sysmex SP-50 to produce blood smears (BS) that reflect the true lymphocyte morphology of patient samples. METHODS: Using different start times of fan1, we obtained a set of 84 blood smear slides from 21 blood samples and measured 10,920 lymphocyte areas, which were then converted to compare lymphocyte sizes. We also performed a leukocyte differential count using Sysmex DI-60 on 202 blood smear slides prepared before and after the change in staining conditions and compared the results. RESULTS: The mean lymphocyte sizes at FAN1ST 0 second, 5 seconds, 10 seconds, and 30 seconds were 12.55 µm, 12.14 µm, 11.27 µm, and 10.50 µm, respectively. The mean differences in the preclassification of neutrophils, lymphocytes, monocytes, eosinophils, and basophils in DI-60, according to the SP-50 staining conditions, were 0.88, -1.58, -0.24, 0.37, and 0.07, respectively. CONCLUSIONS: Wright-Giemsa staining of blood smears prepared on the SP-50 showed that changing the pH of the concentrated phosphate buffer to 6.6 and adjusting the staining time did not affect the results of the leukocyte differential count. However, since fan1 was used to dry the blood smear on the SP-50 and the lymphocyte size gradually decreased as the start time was delayed, it was necessary to set a start time for fan1 that did not affect the lymphocyte size.

Spousal support, parent-nurse partnership and caregiver burden among parents of children with chronic diseases: A cross-sectional study.

AIM: To examine the effects of spousal support and parent-nurse partnership on caregiver burden of parents of children with chronic disease. BACKGROUND: With the trend of increasing the global number of children with chronic diseases, the parental caregiver burden has become increasingly prevalent. DESIGN: Cross-sectional study. METHODS: The study participants included 115 parents of children diagnosed with chronic disease at a general hospital in South Korea. The study duration was 4 June 2021-30 April 2022. Self-reported measures included the parent-nurse partnership scale, the Korean version of the Parenting Alliance Inventory and the family caregiver burden scale. T-tests, ANOVA, Pearson's correlation coefficients and hierarchical linear multiple regression were conducted using IBM SPSS version 26.0. This study followed STROBE guideline. RESULTS: Parental caregiver burden was significantly negatively associated with spousal support and parent-nurse partnership. Factors significantly influencing caregiver burden were parental alcohol consumption; child's inherited metabolic disease, cardiovascular disease, disease relating to haematological tumours or kidney disease diagnosis; child's health perceived as poor by parents; child's dependency perceived as high by parents; hospitalization recency; and low spousal support. These factors accounted for 65% of caregiver burden. CONCLUSION: Parental caregiver burden was related to spousal support and parent-nurse partnership, but the primary factor affecting caregiver burden was spousal support. RELEVANCE TO CLINICAL PRACTICE: The results highlighted the role of healthcare professionals in educating parents of children with chronic diseases to facilitate spousal support and have implications for nursing and community-based interventions to reduce parental caregiver burden. Furthermore, they underlined that policymakers and other stakeholders should pay attention to the parental caregiver burden through government-based, family-centered strategies. PATIENT OR PUBLIC CONTRIBUTION: Parents of children with chronic disease were recruited to perform the self-administered survey in the phase of data collection.

Cross-Sectional and Descriptive Study on the Challenges and Awareness of Hispanic Parents Regarding Their Adolescents' Mental Health during the COVID-19 Pandemic.

Research has shown that during the COVID-19 pandemic, approximately 20% of children and adolescents in the United States experienced mental health issues that became a significant social concern. However, recent studies have demonstrated that the majority of adolescents maintain positive emotions despite the crisis. This cross-sectional and descriptive study delves into the emotional states of adolescents during the pandemic, considering the viewpoints of both adolescents and their parents, with a specific focus on Hispanic adolescents. Survey results revealed that most adolescents reported positive and happy moods. However, a percentage of adolescents experienced worry, significant changes in feelings, and loneliness as a result of the physical and social isolation associated with virtual learning. Unfortunately, most surveyed Hispanic parents did not adequately recognize their adolescents' mood changes well. This lack of awareness, caused by factors such as an insufficient understanding about the importance of adolescent mental health, cultural reasons, language barriers, low education, unstable jobs, and more, could lead to missed opportunities for timely mental health interventions. This study seeks to provide a comprehensive discussion on the mental health of adolescents, while also advocating for the emotional wellbeing of Hispanic adolescents.

Basic knowledge for counseling patients undergoing risk-reducing salpingo-oophorectomy.

Significant progress has been made in the molecular diagnosis of cancer. It provides personalized medicine, including cancer diagnosis, prognosis, targeted therapy, and risk detection. These advances allow physicians to identify patients at risk for cancer before it develops and offer them an opportunity to prevent its development. Mutations in breast cancer susceptibility genes 1 and 2 (BRCA1 and 2) are one of the most well-known cancer-related gene mutations since actor Angelina Jolie shared her experience with genetic mutations and risk-reducing surgery in the media. In Korea, tests for germline BRCA1/2 mutations have been covered by insurance since May 2012 and the number of women of BRCA1/2 mutations has continued to increase over the past decade. Most carriers of BRCA1/2 mutations consider risk-reducing salpingo-oophorectomy (RRSO) resulting in early menopause and want to know the lifetime risks and benefits of RRSO. However, despite the increasing number of carriers of BRCA1/2 mutations, the counseling and management of patients requiring RRSO varies among physicians. This article provides basic knowledge on RRSO to help physicians comprehensively assess its risks and benefits and manage at-risk women.

Trends in forgone medical care and unmet needs among Medicare beneficiaries with a history of depression during the COVID-19 pandemic: a national, repeated cross-sectional study.

OBJECTIVES: To investigate trends in forgone medical care, basic needs disruption, financial and mental health disruption, engagement of preventive behaviours guidelines, and perceived severity of COVID-19 among community-living Medicare beneficiaries in the USA with and without a self-reported history of depression from Summer 2020 to Winter 2021. DESIGN/SETTING: A repeated cross-sectional study using a nationally representative sample of Medicare beneficiaries of three rounds of survey data from the Medicare Current Beneficiary Survey COVID-19 Supplement Public Use Files: Summer 2020, Fall 2020 and Winter 2021. PARTICIPANTS: A total of 28 480 community-dwelling Medicare beneficiaries. MAIN OUTCOME MEASURES: Forgone medical care, basic needs disruption, financial and mental health disruption, engagement of preventive behaviours guidelines, and perceived severity of COVID-19. RESULTS: In the study sample, 7629 (27%) had a history of depression. After adjusting for potential confounders, weighted multivariable logistic regression models showed that Medicare beneficiaries with a history of depression had higher odds of foregone medical care (OR: 1.29, 95% CI 1.16 to 1.42, p<0.001), of basic need disruption (OR: 1.49, 95% CI 1.33 to 1.67, p<0.001), and of financial and mental health disruption (OR: 1.75, 95% CI 1.60 to 1.91, p<0.001) during the COVID-19 pandemic when compared with those without a history of depression. No statistically significant differences were observed in engagement of essential preventive behaviours or perception of COVID-19 severity. CONCLUSIONS: COVID-19 pandemic may exacerbate existing barriers to healthcare access and financial and social needs, possibly leading to persistent unmet needs among Medicare beneficiaries with a history of depression beyond the pandemic.

Association between drinking behaviors, sleep duration, and depressive symptoms.

Excessive alcohol consumption has been consistently linked to depression. This study, utilizing nationwide samples from the Korea National Health and Nutrition Examination Survey (n = 21,440) examined the association between drinking behaviors and depressive symptoms while also exploring the influence of sleep duration on this relationship. Demographic, socioeconomic, and health-related factors were included as covariates in the multivariable logistic regression analysis to assess their relationships with depressive symptoms. Based on their sleep duration, the participants were divided into subgroups to explore how sleep duration affects the relationship between drinking behaviors and depressive symptoms. Moderate alcohol consumption (1-4 times a month) was associated with reduced likelihood of experiencing depressive symptoms in women (p = 0.024), with a similar trend observed among men (p = 0.001). Men who started consuming alcohol before the age of 19 had a higher likelihood of experiencing depressive symptoms (p = 0.048). Only women who consumed more alcohol per occasion (≥ 7 drinks) had higher odds of depressive symptoms (p = 0.001). This study revealed complex factors that influence depressive symptoms, including alcohol consumption and sleep duration. This highlights the importance of tailored interventions based on sleep duration and sociodemographic characteristics for preventing and treating depression.

An Explainable Prediction for Dietary-Related Diseases via Language Models.

Our study harnesses the power of natural language processing (NLP) to explore the relationship between dietary patterns and metabolic health outcomes among Korean adults using data from the Seventh Korea National Health and Nutrition Examination Survey (KNHANES VII). Using Latent Dirichlet Allocation (LDA) analysis, we identified three distinct dietary patterns: "Traditional and Staple", "Communal and Festive", and "Westernized and Convenience-Oriented". These patterns reflect the diversity of dietary preferences in Korea and reveal the cultural and social dimensions influencing eating habits and their potential implications for public health, particularly concerning obesity and metabolic disorders. Integrating NLP-based indices, including sentiment scores and the identified dietary patterns, into our predictive models significantly enhanced the accuracy of obesity and dyslipidemia predictions. This improvement was consistent across various machine learning techniques-XGBoost, LightGBM, and CatBoost-demonstrating the efficacy of NLP methodologies in refining disease prediction models. Our findings underscore the critical role of dietary patterns as indicators of metabolic diseases. The successful application of NLP techniques offers a novel approach to public health and nutritional epidemiology, providing a deeper understanding of the diet-disease nexus. This study contributes to the evolving field of personalized nutrition and emphasizes the potential of leveraging advanced computational tools to inform targeted nutritional interventions and public health strategies aimed at mitigating the prevalence of metabolic disorders in the Korean population.

Sex differences of the association between handgrip strength and health-related quality of life among patients with cancer.

The purpose of this study is to investigate the association between handgrip strength (HGS) and health-related quality of life (HRQoL), demonstrating HGS as an effective indicator for evaluating HRQoL of patients with cancer. Analyzing 1657 Korean adult cancer patients (644 males, 1013 females) aged ≥ 20 years from the Korea National Health and Nutrition Examination Survey (2014-2019), HGS was standardized based on body mass index and categorized by sex. HRQoL was assessed using the Euro Quality of Life-5-Dimension 3-Level version (EQ-5D-3L) Index. Lower relative HGS was associated with decreased HRQoL in female patients, while no significant association was found in male patients. The lowest quartile of relative HGS exhibited a 2.5-fold decrease in HRQoL compared to the highest quartile (OR 2.50, 95% CI 1.59-3.95, p < 0.001). Both male and female patients with cancer were affected by age, subjective health perception, and stress recognition regarding HRQoL. This study suggests that HGS may be associated with the HRQoL of female patients with cancer, emphasizing that the HGS measurement can be effectively utilized as a pivotal tool for evaluating HRQoL in female patients with cancer.

Informal care provided in US nursing homes: Reduced from 2010 to 2021 and lower for Medicaid residents.

BACKGROUND: Little is known about the trend of informal care (unpaid care provided by family or other caregivers) provided to nursing home residents before or during the COVID-19 pandemic. This study assessed this trend during 2010-2021, for all and Medicaid versus non-Medicaid residents. METHODS: Using data from the RAND Health and Retirement Study longitudinal file, our study sample included a total of 2025 resident-years (860 for Medicaid and 1165 for non-Medicaid residents). We fit two-part regression models to determine adjusted trends in average amount of informal care over time, and difference by resident Medicaid status. RESULTS: Informal care received by residents reduced substantially over time, from an average of 39.2 h in the past month of interview in 2010-11 to 23.2 h in 2018-19, and then to 11.2 h in the COVID-19 pandemic (2020-21). The reduced hours were due to both reduced percentages of nursing home residents who received any informal care and reduced hours of care among those who did receive it over time. Multivariable analyses confirmed this trend and similar downward trends for Medicaid versus non-Medicaid residents. Medicaid residents on average received 10.02 fewer hours of informal care per month (95% confidence interval -17.16, -2.87; p = 0.006) than non-Medicaid residents after adjustment for resident characteristics and time trends. CONCLUSION: Informal care provided to nursing home residents during 2010-2021 reduced over time, especially during the COVID-19 pandemic (2020-21). Medicaid residents tended to receive less informal care than non-Medicaid residents.

The role of neurotrophic factors in novel, rapid psychiatric treatments.

Neurotrophic factors are a family of growth factors that modulate cellular growth, survival, and differentiation. For many decades, it has been generally believed that a lack of neurotrophic support led to the decreased neuronal synaptic plasticity, death, and loss of non-neuronal supportive cells seen in neuropsychiatric disorders. Traditional psychiatric medications that lead to immediate increases in neurotransmitter levels at the synapse have been shown also to elevate synaptic neurotrophic levels over weeks, correlating with the time course of the therapeutic effects of these drugs. Recent advances in psychiatric treatments, such as ketamine and psychedelics, have shown a much faster onset of therapeutic effects (within minutes to hours). They have also been shown to lead to a rapid release of neurotrophins into the synapse. This has spurred a significant shift in understanding the role of neurotrophins and how the receptor tyrosine kinases that bind neurotrophins may work in concert with other signaling systems. In this review, this renewed understanding of synaptic receptor signaling interactions and the clinical implications of this mechanistic insight will be discussed within the larger context of the well-established roles of neurotrophic factors in psychiatric disorders and treatments.

A comparative study on eating habits and mental health of Korean middle school students according to their bedtime across regions: using data from the 2020-2022 Korea Youth Risk Behavior Survey.

BACKGROUND/OBJECTIVES: The objective of this study was to compare dietary habits and mental health among middle school students in urban and rural areas based on bedtime, and to provide evidence supporting appropriate bedtime for Korean middle school students in relation to their healthy dietary habits and mental well-being. SUBJECTS/METHODS: The study population consisted of 25,681 second-year middle school students who participated in the Korea Youth Risk Behavior Survey in 2020-2022. Participants were asked about their bedtime and wake-up time during the past 7 days and were classified into five categories. The study compared the general characteristics, academic factors, dietary habits, and mental health of urban and rural students based on their bedtime. RESULTS: Bedtime was found to be later in the following order: urban female students, rural female students, urban male students, and rural male students. As bedtime got later, the rates of smoking and alcohol consumption increased. Students who went to bed before 11 p.m. had lower academic performance, while rural male students who went to bed after 2 a.m. had lower academic performance. Later bedtime was associated with increased smartphone usage, skipping breakfast, consuming fast food, and drinking carbonated beverages. Later bedtime was also associated with higher perceived stress levels, particularly among students who went to bed after 2 a.m., higher rates of suicidal ideation, experiencing sadness and despair, as well as the prevalence of clinically significant anxiety disorders. CONCLUSION: These results suggest that middle school students who go to bed too late have higher rates of smoking and alcohol drinking, as well as unhealthy eating habits, stress, suicidal ideation, sadness, and anxiety. Therefore, it is necessary to provide educational and social institutional support to promote adequate sleep for the health of adolescents.

Trend in Respite Use by Race Among Caregivers for People Living with Dementia.

BACKGROUND: Respite care provides short-term relief for caregivers. Despite efforts to promote respite use among Black caregivers, little is known if disparities in respite use between Black and White dementia caregivers have decreased over time. We examined a trend nationally to see if more recent efforts may have helped reduce disparities in respite use. METHODS: We used a repeated cross-sectional design, with the data from 2015, 2017, and 2021 of the National Health and Aging Trends Study and National Study of Caregiving. Our study sample included 764 (in 2015), 839 (in 2017) and 521 (in 2021) non-Hispanic White and Black caregivers who provided care to older adults living with dementia, representing weighted 5,157,569 (2015), 5,877,997 (2017), and 4,712,144 (2021) dementia caregivers nationally. We conducted logistic regression models to assess the differences in respite use between White and Black caregivers over time. RESULTS: In 2015, Black dementia caregivers had a respite care use rate 11.6 percentage points (95% CI: -16.9 to -6.4) lower than that of White dementia caregivers. However, both in 2017 and 2021, the difference in the use of respite was not statistically significant, leading to a reduced or no gap in respite use between White and Black dementia caregivers. However, respite use remained low in both groups. CONCLUSIONS: Although the gap in respite use between Black and White dementia caregivers had been gradually narrowed over time, more efforts are needed to encourage more respite use among both groups through targeted efforts to address factors that hinder respite use.

Integration of the Natural Language Processing of Structural Information Simplified Molecular-Input Line-Entry System Can Improve the In Vitro Prediction of Human Skin Sensitizers.

Natural language processing (NLP) technology has recently used to predict substance properties based on their Simplified Molecular-Input Line-Entry System (SMILES). We aimed to develop a model predicting human skin sensitizers by integrating text features derived from SMILES with in vitro test outcomes. The dataset on SMILES, physicochemical properties, in vitro tests (DPRA, KeratinoSensTM, h-CLAT, and SENS-IS assays), and human potency categories for 122 substances sourced from the Cosmetics Europe database. The ChemBERTa model was employed to analyze the SMILES of substances. The last hidden layer embedding of ChemBERTa was tested with other features. Given the modest dataset size, we trained five XGBoost models using subsets of the training data, and subsequently employed bagging to create the final model. Notably, the features computed from SMILES played a pivotal role in the model for distinguishing sensitizers and non-sensitizers. The final model demonstrated a classification accuracy of 80% and an AUC-ROC of 0.82, effectively discriminating sensitizers from non-sensitizers. Furthermore, the model exhibited an accuracy of 82% and an AUC-ROC of 0.82 in classifying strong and weak sensitizers. In summary, we demonstrated that the integration of NLP of SMILES with in vitro test results can enhance the prediction of health hazard associated with chemicals.