M6A modification in cardiovascular disease: With a focus on programmed cell death.

N6-methyladenosine (m6A) methylation is one of the most predominant internal RNA modifications in eukaryotes and has become a hot spot in the field of epigenetics in recent years. Cardiovascular diseases (CVDs) are a leading cause of death globally. Emerging evidence demonstrates that RNA modifications, such as the m6A modification, are associated with the development and progression of many diseases, including CVDs. An increasing body of studies has indicated that programmed cell death (PCD) plays a vital role in CVDs. However, the molecular mechanisms underlying m6A modification and PCD in CVDs remain poorly understood. Herein, elaborating on the highly complex connections between the m6A mechanisms and different PCD signaling pathways and clarifying the exact molecular mechanism of m6A modification mediating PCD have significant meaning in developing new strategies for the prevention and therapy of CVDs. There is great potential for clinical application.

Disparities in end-of-life care for minoritized racial and ethnic patients during terminal hospitalizations in New York State.

BACKGROUND: Racial and ethnic minorities often receive care at different hospitals than non-Hispanic white patients, but how hospital characteristics influence the occurrence of disparities at the end of life is unknown. The aim of this study was to determine if disparities in end-of-life care were present among minoritized patients during terminal hospitalizations, and if these disparities varied with hospital characteristics. METHODS: We identified hospitalizations where a patient died in New York State, 2016-2018. Using multilevel logistic regression, we examined whether documented end-of-life care (do-not-resuscitate status (DNR), palliative care (PC) encounter) differed by race and ethnicity, and whether these disparities differed based on receiving care in hospitals with varying characteristics (Black or Hispanic-serving hospital; teaching status; bed size; and availability of specialty palliative care). RESULTS: We identified 143,713 terminal hospitalizations in 188 hospitals. Across all hospitals, only Black patients were less likely to have a PC encounter (adjusted odds ratio (aOR) 0.83 [0.80-0.87]) or DNR status (aOR 0.91 [0.87-0.95]) when compared with non-Hispanic White patients, while Hispanic patients were more likely to have DNR status (aOR 1.07 [1.01-1.13]). In non-teaching hospitals, all minoritized groups had decreased odds of PC (aOR 0.80 [0.76-0.85] for Black, aOR 0.91 [0.85-0.98] for Hispanic, aOR 0.93 [0.88-0.98] for Others), while in teaching hospitals, only Black patients had a decreased likelihood of a PC encounter (aOR 0.88 [0.82-0.93]). Also, Black patients in a Black-serving hospitals were less likely to have DNR status (aOR 0.80 [0.73-0.87]). Disparities did not differ based on whether specialty PC was available (p = 0.27 for PC encounter, p = 0.59 for DNR status). CONCLUSION: During terminal hospitalizations, Black patients were less likely than non-Hispanic White patients to have documented end-of-life care. This disparity appears to be more pronounced in non-teaching hospitals than in teaching hospitals.

[Humoral Immunity Abnormalities in Advanced Maternal-Age Women With Recurrent Spontaneous Abortion: A Single Center Study]. / é«˜é¾„å¤å‘æ€§æµäº§æ‚£è€ ä½“æ¶²å ç–«å¼‚å¸¸çš„å•ä¸­å¿ƒç ”ç©¶.

Objective: To determine the humoral immunity in advanced maternal-age women with recurrent spontaneous abortion (RSA). Methods: A retrospective study was performed between January 2022 and October 2023 in the Department of Reproductive Immunity of Shanghai First Maternity and Infant Hospital. Women with RSA were recruited and multiple autoantibodies were tested. Multivariate logistic regression was performed to compare the associations between different age groups (20 to 34 years old in the low maternal-age group and 35 to 45 years in the advanced maternal-age group) and multiple autoantibodies, while controlling for three confounding factors, including body mass index (BMI), previous history of live birth, and the number of spontaneous abortions. Then, we investigated the differences in the humoral immunity of advanced maternal-age RSA women and low maternal-age RSA women. Result: A total of 4009 women with RSA were covered in the study. Among them, 1158 women were in the advanced maternal-age group and 2851 women were in the low maternal-age group. The prevalence of antiphospholipid syndrome, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease was 15.6% and 14.1%, 0.0% and 0.1%, 0.9% and 0.9%, 0.3% and 0.0%, and 23.7% and 22.6% in the advanced maternal-age group and low maternal-age group, respectively, showing no statistical difference between the two groups. The positive rates of antiphospholipid antibodies (aPLs), antinuclear antibody (ANA), extractable nuclear antigen (ENA) antibody, anti-double stranded DNA (dsDNA) antibody, anti single-stranded DNA (ssDAN) antibody, antibodies against alpha-fodrin (AAA), and thyroid autoimmunity (TAI) were 19.1% and 19.5%, 6.6% and 6.6%, 9.2% and 10.5%, 2.0% and 2.0%, 2.2% and 1.2%, 5.1% and 4.9%, and 17.8% and 16.8%, respectively. No differences were observed between the two groups. 1.6% of the women in the advanced maternal-age group tested positive for lupus anticoagulant (LA), while 2.7% of the women in the low maternal-age group were LA positive, with the differences being statistically significant (odds ratio=0.36, 95% confidence interval: 0.17-0.78). In the 4008 RSA patients, the cumulative cases tested positive for the three antibodies of the aPLs spectrum were 778, of which 520 cases were positive for anti-ß2 glycoprotein Ⅰ antibodies (ß2GPⅠ Ab)-IgG/IgM, 58 were positive for aCL-IgG/IgM, 73 were positive for LA, 105 were positive for both ß2GPⅠ Ab-IgG/IgM and aCL-IgG/IgM, 17 were positive for both ß2GPⅠ Ab-IgG/IgM and LA, 2 were positive for both aCL-IgG/IgM and LA, and 3 were positive for all three antibodies. Conclusion: Our study did not find a difference in humoral immunity between RSA women of advanced maternal age and those of low maternal age.

New information about the cyclable capacity fading process of a pouch cell with Li-rich layered oxide cathodes.

Most studies investigate the cyclable capacity fading mechanism of Li-rich layered oxides (LLOs) from the microscopic structure level, lacking discussions about how the structure degradation influences the performance of the pouch cell precisely and quantitatively. Based on the analysis of the evolution of key parameters during the whole cycling period, a new transition-type fading mechanism is proposed. From the early-to-middle stage of the cycling period, polarization increases, most of which is interface-related, causing about 67% of the whole capacity loss. From the middle-to-late stage of the cycling period, active material losses turn out to be the dominating factor, inducing about 61% of the total capacity loss. Diffusion-related polarization, replacing the interface type, is responsible for most of the increased overpotential. Relative analysis confirms that during the early stage, the increase of the charge transfer resistance, induced by CEI (cathode electrolyte interface) growth and initial surface layered-structure degradation, is the main source of interface polarization. As the cycling evolves to the late stage, severe bulky structure degradation, including lattice-oxygen release, Li/Ni mixture and generation of a new spinel phase, turns out to be the major factor, causing further capacity fading.

Diabetes mellitus and hard braking events in older adult drivers.

BACKGROUND: Diabetes mellitus (DM) can impair driving safety due to hypoglycemia, hyperglycemia, diabetic peripheral neuropathy, and diabetic eye diseases. However, few studies have examined the association between DM and driving safety in older adults based on naturalistic driving data. METHODS: Data for this study came from a multisite naturalistic driving study of drivers aged 65-79 years at baseline. Driving data for the study participants were recorded by in-vehicle recording devices for up to 44 months. We used multivariable negative binomial modeling to estimate adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) of hard braking events (HBEs, defined as maneuvers with deceleration rates ≥ 0.4 g) associated with DM. RESULTS: Of the 2856 study participants eligible for this analysis, 482 (16.9%) reported having DM at baseline, including 354 (12.4%) insulin non-users and 128 (4.5%) insulin users. The incidence rates of HBEs per 1000 miles were 1.13 for drivers without DM, 1.15 for drivers with DM not using insulin, and 1.77 for drivers with DM using insulin. Compared to drivers without DM, the risk of HBEs was 48% higher for drivers with DM using insulin (aIRR 1.48; 95% CI: 1.43, 1.53). CONCLUSION: Older adult drivers with DM using insulin appear to be at increased proneness to vehicular crashes. Driving safety should be taken into consideration in DM care and management.

Posterior scleritis following a single infusion of zoledronate for osteoporosis: A case report and literature review.

The most frequently reported adverse reaction to zoledronic acid is an acute phase reaction resembling influenza. While rarer adverse events such as osteonecrosis of the jaw and atypical femoral fractures have gained significant recognition, the ocular adverse effects, particularly scleritis, are not yet fully comprehended. Here, we present the case of a 75-year-old female patient with osteoporosis who developed bilateral redness and intense eye pain 48 h after receiving a 5 mg intravenous dose of zoledronic acid. Clinical presentation suggested bilateral conjunctivitis, but treatment with levofloxacin eye drops and acyclovir ophthalmic gel exacerbated the symptoms over 2 days, predominantly affecting the left eye. Ocular ultrasonography revealed thickening of the left eyeball wall with a "T" sign, while an orbital CT scan showed increased thickness of the left sclera. Treatment with methylprednisolone 80 mg intravenous infusion twice daily led to gradual symptom improvement and eventual resolution of inflammation. This report, based on a review of relevant literature, investigates the treatment and outcomes of zoledronic acid-induced scleritis, emphasizing the importance for clinicians to promptly identify and manage this rare and serious ocular adverse reaction.

Disease Occurrence and Climatic Factors Jointly Structure Pomelo Leaf Fungal Succession in Disturbed Agricultural Ecosystem.

For perennial plants, newly emerged organs are fresh hot spots for environmental microbes to occupy and assemble to form mature microbial communities. In the microbial community, some commensal fungi can play important roles in microbial succession, thus significantly improving host plant growth and disease resistance. However, their participating patterns in microbial assembly and succession remain largely unknown. In this study, we profiled the fungal community and found a similar fungal succession pattern of spring-emerged leaves from March to October in two pomelo orchards. Specifically, the fungal species, tracked on the old leaves, dominated the spring leaves after emergence and then decreased in relative abundance. This reduction in priority effects on the spring leaves was then followed by an increase in the number of observed species, Shannon and phylogenetic diversity indices, and the pathogen-associated fungal groups. In addition, we found that the temporal fungal succession on the spring leaves highly correlated with the disease occurrence in the orchards and with the temperature and precipitation variation from spring to summer. Of the pathogen-associated fungal groups, an increase in the relative abundance of Mycosphaerellaceae, hosting the causal agent of citrus greasy spot, correlated with the occurrence of the disease, while the relative abundance of Diaporthaceae, hosting the causal agent of melanose, was extremely low during the fungal succession. These results confirm that the two kinds of pathogen-associated fungal groups share different lifestyles on citrus, and also suggest that the study of temporal fungal succession in microbial communities can add to our understanding of the epidemiology of potential plant pathogens.

Frailty and poor physical functioning as risk factors for driving cessation.

Introduction: Frailty and low physical performance are modifiable factors and, therefore, targets for interventions aimed at delaying driving cessation (DC). The objective was to determine the impact of frailty and physical performance on DC. Methods: Multisite prospective cohort of older drivers. The key inclusion criteria are as follows: active driver age 65-79 years, possessing a valid driver's license, without significant cognitive impairment, and driving a 1996 car or a newer model car. Of the 2,990 enrolled participants, 2,986 (99.9%) had at least one frailty or Short Physical Performance Battery (SPPB) measure and were included in this study. In total, 42% of participants were aged 65-69 years, 86% were non-Hispanic white, 53% were female, 63% were married, and 41% had a high degree of education. The Fried Frailty Phenotype and the Expanded Short Physical Performance Battery (SPPB) from the National Health and Aging Trends Study were utilized. At each annual visit, DC was assessed by the participant notifying the study team or self-reporting after no driving activity for at least 30 days, verified via GPS. Cox proportional hazard models, including time-varying covariates, were used to examine the impact of the SPPB and frailty scores on time to DC. This assessment included examining interactions by sex. Results: Seventy-three participants (2.4%) stopped driving by the end of year 5. Among women with a fair SPPB score, the adjusted hazard ratio (HR) of DC was 0.26 (95% confidence interval (CI) 0.10-0.65) compared to those with a poor SPPB score. For those with a good SPPB score, the adjusted HR of DC had a p-value of <0.001. Among men with a fair SPPB score, the adjusted hazard ratio (HR) of DC was 0.45 (95% CI 0.25-0.81) compared to those with a poor SPPB score. For men with a good SPPB score, the adjusted HR of DC was 0.19 (95% CI 0.10-0.36). Sex was not an effect modifier between frailty and DC. For those who were categorized into pre-frail or frail, the adjusted ratio of HR to DC was 6.1 (95% CI 2.7-13.8) compared to those who were not frail. Conclusion and relevance: Frailty and poor physical functioning are major risk factors for driving cessation. Staying physically active may help older adults to extend their driving life expectancy and mobility.

miR-652-3p Suppressed the Protective Effects of Isoflurane Against Myocardial Injury in Hypoxia/Reoxygenation by Targeting ISL1.

This research is concentrated on investigating the role and mechanism of miR-652-3p in the protective effects of isoflurane (ISO) against myocardial ischemia-reperfusion (I/R) injury. H9c2 cells underwent pretreatment with varying concentrations of ISO, and subsequently, a hypoxia/reoxygenation (H/R) model was constructed. The levels of miR-652-3p, ISL LIM homeobox 1 (ISL1), and inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) were evaluated through reverse transcription polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay was employed to investigate concentrations of myocardial injury markers, such as creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI). Cell counting kit-8 was used to evaluate cell viability, while flow cytometry was utilized to measure apoptosis. Additionally, a dual luciferase reporter assay was conducted to validate the targeting relationship between ISL1 and miR-652-3p. Herein, we confirmed that the level of miR-652-3p was gradually increased with prolonged hypoxia; nevertheless, this increase was suppressed by ISO pretreatment (P < 0.05). Additionally, ISO pretreatment prevented the decrease in cell viability, increase in apoptosis, and overproduction of IL-6, TNF-α, CK-MB, and cTnI induced by H/R (P < 0.05). However, the inhibitory effects of ISO were counteracted by the increased levels of miR-652-3p (P < 0.05). ISL1 is a potential target of miR-652-3p. H/R induction suppressed ISL1 levels compared to the control, but ISO treatment increased its expression (P < 0.05). Overexpression of ISL1 inhibited the elimination of the protective effect of ISO on myocardial damage induced by the elevation of miR-652-3p (P < 0.05). The findings of this research confirm that miR-652-3p attenuated the protective effect of ISO on cardiomyocytes in myocardial ischemia by targeting ISL1.

Behavioural and neuropsychological outcomes in children exposed in utero to maternal labour epidural analgesia.

BACKGROUND: Recent studies report conflicting results regarding the relationship between labour epidural analgesia (LEA) in mothers and neurodevelopmental disorders in their offspring. We evaluated behavioural and neuropsychological test scores in children of mothers who used LEA. METHODS: Children enrolled in the Raine Study from Western Australia and delivered vaginally from a singleton pregnancy between 1989 and 1992 were evaluated. Children exposed to LEA were compared with unexposed children. The primary outcome was the parent-reported Child Behaviour Checklist (CBCL) reporting total, internalising, and externalising behavioural problem scores at age 10 yr. Score differences, an increased risk of clinical deficit, and a dose-response based on the duration of LEA exposure were assessed. Secondary outcomes included language, motor function, cognition, and autistic traits. RESULTS: Of 2180 children, 850 (39.0%) were exposed to LEA. After adjustment for covariates, exposed children had minimally increased CBCL total scores (+1.41 points; 95% confidence interval [CI] 0.09 to 2.73; P=0.037), but not internalising (+1.13 points; 95% CI -0.08 to 2.34; P=0.066) or externalising (+1.08 points; 95% CI -0.08 to 2.24; P=0.068) subscale subscores. Increased risk of clinical deficit was not observed for any CBCL score. For secondary outcomes, score differences were inconsistently observed in motor function and cognition. Increased exposure duration was not associated with worse scores in any outcomes. CONCLUSIONS: Although LEA exposure was associated with slightly higher total behavioural scores, there was no difference in subscores, increased risk of clinical deficits, or dose-response relationship. These results argue against LEA exposure being associated with consistent, clinically significant neurodevelopmental deficits in children.

Evaluation of ERCP-related perforation: a single-center retrospective study.

Background: Endoscopic retrograde cholangiopancreatography (ERCP)-related perforation is a rare and serious adverse event. The aim of our study was to evaluate the risk factors and management of ERCP-related perforation, and to further determine the predictive factors associated with perforation outcome. Methods: A total of 27,018 ERCP procedures performed at the First Affiliated Hospital of Nanchang University (Nanchang, China) between January 2007 and March 2022 were included in the investigation of ERCP-related perforation. Medical records and endoscopic data were extracted to analyse the risk factors, management, and clinical outcome of ERCP-related perforation. Results: Seventy-six patients (0.28%) were identified as having experienced perforation following ERCP. Advanced age, Billroth II anatomy, precut sphincterotomy, and papillary balloon dilatation were significantly associated with ERCP-related perforation. Most patients with perforation (n = 65) were recognized immediately during ERCP whereas 11 were recognized later on. The delay in recognition primarily resulted from stent migration (n = 9). In addition, 12 patients experienced poor clinical outcome including death or hospice discharge (n = 3), ICU admission for >3 days (n = 6), and prolonged hospital stay for >1 month due to perforation (n = 3). Cancer and systemic inflammatory response syndrome (SIRS) are associated with a higher risk of poor outcome. Conclusions: Advanced age, Billroth II anatomy, precut sphincterotomy, and balloon dilation increase the risk of ERCP-related perforation whereas cancer and SIRS independently predicted poor clinical outcome.

Unveiling convergent and divergent intrinsic brain network alternations in depressed adolescents engaged in non-suicidal self-injurious behaviors with and without suicide attempts.

AIMS: Limited understanding exists regarding the neurobiological mechanisms underlying non-suicidal self-injury (NSSI) and suicide attempts (SA) in depressed adolescents. The maturation of brain network is crucial during adolescence, yet the abnormal alternations in depressed adolescents with NSSI or NSSI+SA remain poorly understood. METHODS: Resting-state functional magnetic resonance imaging data were collected from 114 depressed adolescents, classified into three groups: clinical control (non-self-harm), NSSI only, and NSSI+SA based on self-harm history. The alternations of resting-state functional connectivity (RSFC) were identified through support vector machine-based classification. RESULTS: Convergent alterations in NSSI and NSSI+SA predominantly centered on the inter-network RSFC between the Limbic network and the three core neurocognitive networks (SalVAttn, Control, and Default networks). Divergent alterations in the NSSI+SA group primarily focused on the Visual, Limbic, and Subcortical networks. Additionally, the severity of depressive symptoms only showed a significant correlation with altered RSFCs between Limbic and DorsAttn or Visual networks, strengthening the fact that increased depression severity alone does not fully explain observed FC alternations in the NSSI+SA group. CONCLUSION: Convergent alterations suggest a shared neurobiological mechanism along the self-destructiveness continuum. Divergent alterations may indicate biomarkers differentiating risk for SA, informing neurobiologically guided interventions.

Association between polypharmacy and hard braking events in older adult drivers.

BACKGROUND: Polypharmacy (i.e., simultaneous use of two or more medications) poses a serious safety concern for older drivers. This study assesses the association between polypharmacy and hard braking events in older adult drivers. METHODS: Data for this study came from a naturalistic driving study of 2990 older adults. Information about medications was collected through the "brown-bag review" method. Primary vehicles of the study participants were instrumented with data recording devices for up to 44 months. Multivariable negative binomial model was used to estimate the adjusted incidence rate ratios (aIRRs) and 95 % confidence intervals (CIs) of hard-braking events (i.e., maneuvers with linear deceleration rates ≥0.4 g) associated with polypharmacy. RESULTS: Of the 2990 participants, 2872 (96.1 %) were eligible for this analysis. At the time of enrollment, 157 (5.5 %) drivers were taking fewer than two medications, 904 (31.5 %) were taking 2-5 medications, 895 (31.2 %) were taking 6-9 medications, 571 (19.9 %) were taking 10-13 medications, and 345 (12.0 %) were taking 14 or more medications. Compared to drivers using fewer than two medications, the risk of hard-braking events increased 8 % (aIRR 1.08, 95 % CI 1.04, 1.13) for users of 2-5 medications, 12 % (aIRR 1.12, 95 % CI 1.08, 1.16) for users of 6-9 medications, 19 % (aIRR 1.19, 95 % CI 1.15, 1.24) for users of 10-13 medications, and 34 % (aIRR 1.34, 95 % CI 1.29, 1.40) for users of 14 or more medications. CONCLUSIONS: Polypharmacy in older adult drivers is associated with significantly increased incidence of hard-braking events in a dose-response fashion. Effective interventions to reduce polypharmacy use may help improve driving safety in older adults.

PBAC: A pathway-based attention convolution neural network for predicting clinical drug treatment responses.

Precise and personalized drug application is crucial in the clinical treatment of complex diseases. Although neural networks offer a new approach to improving drug strategies, their internal structure is difficult to interpret. Here, we propose PBAC (Pathway-Based Attention Convolution neural network), which integrates a deep learning framework and attention mechanism to address the complex biological pathway information, thereby provide a biology function-based robust drug responsiveness prediction model. PBAC has four layers: gene-pathway layer, attention layer, convolution layer and fully connected layer. PBAC improves the performance of predicting drug responsiveness by focusing on important pathways, helping us understand the mechanism of drug action in diseases. We validated the PBAC model using data from four chemotherapy drugs (Bortezomib, Cisplatin, Docetaxel and Paclitaxel) and 11 immunotherapy datasets. In the majority of datasets, PBAC exhibits superior performance compared to traditional machine learning methods and other research approaches (area under curve = 0.81, the area under the precision-recall curve = 0.73). Using PBAC attention layer output, we identified some pathways as potential core cancer regulators, providing good interpretability for drug treatment prediction. In summary, we presented PBAC, a powerful tool to predict drug responsiveness based on the biology pathway information and explore the potential cancer-driving pathways.

State cannabis laws and cannabis positivity among fatally injured drivers.

BACKGROUND: As of November 8, 2023, 24 states and the District of Columbia have legalized cannabis for both recreational and medical use (RMCL-states), 14 states have legalized cannabis for medical use only (MCL-states) and 12 states have no comprehensive cannabis legislation (NoCL-states). As more states legalize cannabis for recreational use, it is critical to understand the impact of such policies on driving safety. METHODS: Using the 2019 and 2020 Fatality Analysis Reporting System data, we performed multivariable logistic regression modeling to explore the association between state level legalization status and cannabis positivity using toxicological testing data for 14,079 fatally injured drivers. We performed a sensitivity analysis by including multiply imputed toxicological testing data for the 14,876 eligible drivers with missing toxicological testing data. RESULTS: Overall, 4702 (33.4%) of the 14,079 fatally injured drivers tested positive for cannabis use. The prevalence of cannabis positivity was 30.7% in NoCL-states, 32.8% in MCL-states, and 38.2% in RMCL-states (p < 0.001). Compared to drivers fatally injured in NoCL-states, the adjusted odds ratios of testing positive for cannabis were 1.09 (95% confidence interval: 0.99, 1.19) for those fatally injured in MCL-states and 1.54 (95% confidence interval: 1.34, 1.77) for those fatally injured in RMCL-states. Sensitivity analysis yielded similar results. CONCLUSIONS: Over one-third of fatally injured drivers tested positive for cannabis use. Drivers fatally injured in states with laws permitting recreational use of cannabis were significantly more likely to test positive for cannabis use than those in states without such laws. State medical cannabis laws had little impact on the odds of cannabis positivity among fatally injured drivers.

Association of Disrupted Delta Wave Activity During Sleep With Long-Term Cardiovascular Disease and Mortality.

BACKGROUND: Delta wave activity is a prominent feature of deep sleep, which is significantly associated with sleep quality. OBJECTIVES: The authors hypothesized that delta wave activity disruption during sleep could predict long-term cardiovascular disease (CVD) and CVD mortality risk. METHODS: The authors used a comprehensive power spectral entropy-based method to assess delta wave activity during sleep based on overnight polysomnograms in 4,058 participants in the SHHS (Sleep Heart Health Study) and 2,193 participants in the MrOS (Osteoporotic Fractures in Men Study) Sleep study. RESULTS: During 11.0 ± 2.8 years of follow-up in SHHS, 729 participants had incident CVD and 192 participants died due to CVD. During 15.5 ± 4.4 years of follow-up in MrOS, 547 participants had incident CVD, and 391 died due to CVD. In multivariable Cox regression models, lower delta wave entropy during sleep was associated with higher risk of coronary heart disease (SHHS: HR: 1.46; 95% CI: 1.02-2.06; P = 0.03; MrOS: HR: 1.79; 95% CI: 1.17-2.73; P < 0.01), CVD (SHHS: HR: 1.60; 95% CI: 1.21-2.11; P < 0.01; MrOS: HR: 1.43; 95% CI: 1.00-2.05; P = 0.05), and CVD mortality (SHHS: HR: 1.94; 95% CI: 1.18-3.18; P < 0.01; MrOS: HR: 1.66; 95% CI: 1.12-2.47; P = 0.01) after adjusting for covariates. The Shapley Additive Explanations method indicates that low delta wave entropy was more predictive of coronary heart disease, CVD, and CVD mortality risks than conventional sleep parameters. CONCLUSIONS: The results suggest that delta wave activity disruption during sleep may be a useful metric to identify those at increased risk for CVD and CVD mortality.

Integrated bacterial transcriptome and host metabolome analysis reveals insights into "Candidatus Liberibacter asiaticus" population dynamics in the fruit pith of three citrus cultivars with different tolerance.

"Candidatus Liberibacter asiaticus" (CLas), the causal agent of citrus Huanglongbing (HLB), is able to multiply to a high abundance in citrus fruit pith. However, little is known about the biological processes and phytochemical substances that are vital for CLas colonization and growth in fruit pith. In this study, CLas-infected fruit pith of three citrus cultivars ("Shatangju" mandarin, "Guanxi" pomelo, and "Shatian" pomelo) exhibiting different tolerance to CLas were collected and used for dual RNA-Seq and untargeted metabolome analysis. Comparative transcriptome analysis found that the activation of the CLas noncyclic TCA pathway and pathogenic-related effectors could contribute to the colonization and growth of CLas in fruit pith. The pre-established Type 2 prophage in the CLas genome and the induction of its CRISPR/cas system could enhance the phage resistance of CLas and, in turn, facilitate CLas population growth in fruit pith. CLas infection caused the accumulation of amino acids that were correlated with tolerance to CLas. The accumulation of most sugars and organic acids in CLas-infected fruit pith, which could be due to the phloem blockage caused by CLas infection, was thought to be beneficial for CLas growth in localized phloem tissue. The higher levels of flavonoids and terpenoids in the fruit pith of CLas-tolerant cultivars, particularly those known for their antimicrobial properties, could hinder the growth of CLas. This study advances our understanding of CLas multiplication in fruit pith and offers novel insight into metabolites that could be responsible for tolerance to CLas or essential to CLas population growth.IMPORTANCECitrus Huanglongbing (HLB, also called citrus greening disease) is a highly destructive disease currently threatening citrus production worldwide. HLB is caused by an unculturable bacterial pathogen, "Candidatus Liberibacter asiaticus" (CLas). However, the mechanism of CLas colonization and growth in citrus hosts is poorly understood. In this study, we utilized the fruit pith tissue, which was able to maintain the CLas at a high abundance, as the materials for dual RNA-Seq and untargeted metabolome analysis, aiming to reveal the biological processes and phytochemical substances that are vital for CLas colonization and growth. We provided a genome-wide CLas transcriptome landscape in the fruit pith of three citrus cultivars with different tolerance and identified the important genes/pathways that contribute to CLas colonization and growth in the fruit pith. Metabolome profiling identified the key metabolites, which were mainly affected by CLas infection and influenced the population dynamic of CLas in fruit pith.

Association of Depression and Antidepressant Use With Driving Behaviors in Older Adults: A LongROAD Study.

Older adults aged 70 and older who drive have higher crash death rates per mile driven compared to middle aged (35-54 years) adults who drive in the US. Prior studies have found that depression and or antidepressant medication use in older adults are associated with an increase in the vehicular crash rate. Using data from the prospective multi-site AAA Longitudinal Research on Aging Drivers Study, this analysis examined the independent and interdependent associations of self-reported depression and antidepressant use with driving behaviors that can increase motor vehicle crash risk such as hard braking, speeding, and night-time driving in adults over age 65. Of the 2951 participants, 6.4% reported having depression and 21.9% were on an antidepressant medication. Correcting for age, race, gender, and education level, participants on an antidepressant had increased hard braking events (1.22 [1.10-1.34]) but self-reported depression alone was not associated with changes in driving behaviors.