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Abstract When faced with difficult choices, the possible outcomes are considered through a process known as deliberation. In rats, deliberation is thought to be reflected by pause-and-reorienting behaviors, better known as vicarious trial and errors (VTEs). While VTEs are thought to require medial prefrontal cortex (mPFC) and dorsal hippocampal (dHPC) interactions, no empirical evidence has yet demonstrated such a dual requirement. The nucleus reuniens (Re) of the ventral midline thalamus is anatomically connected with both the mPFC and dHPC, is required for HPC-dependent spatial memory tasks, and is critical for mPFC-dHPC neural synchronization. Currently, it is unclear if, or how, the Re is involved in deliberation. Therefore, by examining the role of the Re on VTE behaviors, we can better understand the anatomical and physiological mechanisms supporting deliberation. Here, we examined the impact of Re suppression on VTE behaviors and mPFC-dHPC theta synchrony during asymptotic performance of a HPC-dependent delayed alternation (DA) task. Pharmacological suppression of the Re increased VTE behaviors that occurred with repetitive choice errors. These errors were best characterized as perseverative behaviors, in which some rats repeatedly selected a goal arm that previously yielded no reward. We then examined the impact of Re suppression on mPFC-dHPC theta synchrony during VTEs. We found that during VTEs, Re inactivation was associated with a reduction in mPFC-dHPC theta coherence and mPFC-to-dHPC theta directionality. Our findings suggest that the Re contributes to deliberation by coordinating mPFC-dHPC neural interactions.

Abstract Post-traumatic stress disorder (PTSD), which frequently occurs in the aftermath of a psychologically traumatic event is characterized by heightened inflammation. People with PTSD also suffer from a number of comorbid clinical and behavioral disorders that are related to chronic inflammation. Thus, understanding the mechanisms of enhanced inflammation in PTSD can provide insights into the relationship between PTSD and associated comorbid disorders. In the current study, we investigated the role of large intervening non-coding RNAs (lincRNAs) in the regulation of inflammation in people diagnosed with PTSD. We observed that WNT ligand, WNT10B, was upregulated in the peripheral blood mononuclear cells (PBMCs) of PTSD patients. This observation was associated with higher H3K4me3 signals around WNT10B promotor in PTSD patients compared to those without PTSD. Increased H3K4me3 resulted from LINC00926, which we found to be upregulated in the PTSD sample, bringing in histone methyltransferase, MLL1, onto WNT10B promotor leading to the introduction of H3K4 trimethylation. The addition of recombinant human WNT10B to pre-activated peripheral blood mononuclear cells (PBMCs) led to increased expression of inflammatory genes such as IFNG and IL17A, suggesting that WNT10B is involved in their upregulation. Together, our data suggested that LINC00926 interacts physically with MLL1 and thereby controls the expression of IFNG and IL17A. This is the first time a long non-coding RNA is shown to regulate the expression of WNT10B and consequently inflammation. This observation has high relevance to our understanding of disease mechanisms of PTSD and comorbidities associated with PTSD.

This article describes recent efforts by Wake Forest University to develop a campus-wide mentoring culture to support holistic student development, to assist with the critical transition from high school to college to life after college, and to develop skills and practices that will be valued by employers and graduate schools. The article describes how the University's Mentoring Resource Center has been developed and uses a decentralized model of mentoring to support mentor and mentee skill development with online and in-person tools and strategies. The article in particular describes several key peer mentoring programs as examples of diverse program goals and participants that are supporting student transition and development. Finally, the article looks at measures of success and lessons learned that can be applied in the future.

Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in stress regulation and in the etiologic basis of stress related disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the purpose and methods of an international consortium that was developed to study the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric Genomics Consortium, we brought together investigators representing seven cohorts with a collective sample size of N = 1147 that included detailed information on trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The objective of this consortium is to increase the analytical sample size by pooling data and combining expertise so that DNA methylation patterns associated with PTSD can be identified. Several quality control and analytical pipelines were evaluated for their control of genomic inflation and technical artifacts with a joint analysis procedure established to derive comparable data over the cohorts for meta-analysis. We propose methods to deal with ancestry population stratification and type I error inflation and discuss the advantages and disadvantages of applying robust error estimates. To evaluate our pipeline, we report results from an epigenome-wide association study (EWAS) of age, which is a well-characterized phenotype with known epigenetic associations. Overall, while EWAS are highly complex and subject to similar challenges as genome-wide association studies (GWAS), we demonstrate that an epigenetic meta-analysis with a relatively modest sample size can be well-powered to identify epigenetic associations. Our pipeline can be used as a framework for consortium efforts for EWAS.

Introduction: Military sexual trauma (MST) is more common among post-9/11 Veterans and women versus older Veterans and men. Despite mandatory screening, the concordance of electronic health record (EHR) documentation and survey-reported MST, and associations with health care utilization and mental health diagnoses, are unknown for this younger group. Materials and Methods: Veterans' Health Administration (VHA) EHR (2001–2021) were merged with data from the observational, nationwide WomenVeterans Cohort Study (collected 2016–2020, n = 1058; 51% women). Experiencing MST was defined as positive endorsement of sexual harassment and/or assault. From the EHR, we derived Veterans' number of primary care and mental health visits in the initial two years of VHA care and diagnoses of posttraumatic stress disorder (PTSD), depression, and anxiety. First, the concordance of EHR MST screening and survey-reported MST was compared. Next, multivariate analyses tested the cross-sectional associations of EHR screening and survey-reported MST with Veterans' health care utilization, and compared the likelihood of PTSD, depression, and anxiety diagnoses by MST group, while covarying demographics and service-related characteristics. With few MST cases among men, multivariate analyses were only pursued for women. Results: Overall, 29% of women and 2% of men screened positive for MST in the EHR, but 64% of women and 9% of men had survey-reported MST. Primary care utilization was similar between women with concordant, positive MST reports in the EHR and survey versus those with survey-reported MST only. Women with survey-reported MST only were less likely to have a PTSD or depression diagnosis than those with concordant, positive MST reports. There was no group difference in women's likelihood of anxiety. Conclusions: EHR MST documentation is discordant for many post-9/11 Veterans—both for men and women. Improving MST screening and better supporting MST disclosure are each critical to provide appropriate and timely care for younger Veterans, particularly women. [ABSTRACT FROM AUTHOR]

We examined potential biases in decisions to use force in a unique way using the shooter task (shoot/don't shoot a Black or White target as quickly as possible) while tracking eye movements. Results showed that participants shot an unarmed White target faster and more often than an unarmed Black target. When examining participants' eye movements, the results showed that when a target was armed, participants may have utilized the stereotype that Blacks are dangerous. On the other hand, when unarmed, the data suggests a story that goes against the stereotype that Whites are safe. This data suggests that biased eye movements may be important in decision-making, which helps us identify what may need to be taught to eliminate shooter biases. This information could assist in police training exercises to reduce bias or "unlearn" stereotypical responses and, thus, have beneficial consequences on the decision to shoot. [ABSTRACT FROM AUTHOR]

Purpose of Review: Significant inequities persist in hypertension detection and control, with minoritized populations disproportionately experiencing organ damage and premature death due to uncontrolled hypertension. Remote blood pressure monitoring combined with telehealth visits (RBPM) is proving to be an effective strategy for controlling hypertension. Yet there are challenges related to technology adoption, patient engagement and social determinants of health (SDoH), contributing to disparities in patient outcomes. This review summarizes the evidence to date for RBPM, focusing on the potential to advance health equity in blood pressure control and the existing levers for largescale implementation. Recent Findings: Several studies demonstrate the promise of RBPM programs to address health disparities through: (1) the use of cellular-enabled blood pressure machines that do not require internet access or smart devices to connect readings into the medical record; (2) emphasis on home blood pressure monitoring to illuminate the daily factors that influence blood pressure control, thereby increasing patient empowerment; (3) adoption of standardized algorithms for hypertension management; and (4) integration of services to address SDoH. Multidisciplinary, non-physician care teams that include nurses, pharmacists, and community health workers are integral to this model. However, most studies have not embraced all aspects of RBPM, and implementation is challenging as current payment models do not support the digital components of RBPM or a diverse workforce of hypertension providers. Conclusion: To address hypertension disparities, RBPM programs need to integrate digital technology that is accessible to all users as well as multidisciplinary care teams that attend to the medical and social needs of populations experiencing health inequities. [ABSTRACT FROM AUTHOR]

Healthcare professionals recommending dietary changes to patients often find that institutional settings—businesses, universities, long-term care facilities, correctional institutions, among others—may not provide the healthful foods that healthcare professionals recommend. Moreover, such institutions encounter an increasing diversity of dietary restrictions, based on allergies, intolerances, religious mandates, or other reasons, that may be challenging to satisfy. To address these issues, experts in health, dietetics, culinary arts, religion, and ethics developed a simple set of guidelines that aim to meet the widest possible range of dietary needs. Three culinary teams then used these guidelines to create "Universal Meals"—simple recipes that were then adapted to larger production sizes for institutional use. The healthfulness of representative sets of meals drawn from these recipes was assessed using the Alternative Healthy Eating Index-2010 and found to be superior to that of a meal pattern based on National Health and Nutrition Examination Survey data. [ABSTRACT FROM AUTHOR]

Introduction: The Faroe Islands are a small archipelago located in the North Atlantic likely colonized by a small group of founders sometime between 50 and 300 CE. Post colonization, the Faroese people have been largely isolated from admixture with mainland and other island populations in the region. As such, the initial founder effect and subsequent genetic drift are likely major contributors to the modern genetic diversity found among the Faroese. Methods: In this study, we assess the utility of Y-chromosomal microsatellites to detect founder effect in the Faroe Islands through the construction of haplotype networks and a novel empirical method, mutational distance from modal haplotype histograms (MDM), for the visualization and evaluation of population bottlenecks. Results: We compared samples from the Faroe Islands and Iceland to possible regional source populations and documented a loss of diversity associated with founder events. Additionally, within-haplogroup diversity statistics reveal lower haplotype diversity and richness within both the Faroe Islands and Iceland, consistent with a small founder population colonizing both regions. However, in the within haplogroup networks, the Faroe Islands are found within the larger set of potential source populations while Iceland is consistently found on isolated branches. Moreover, comparisons of within-haplogroup MDM histograms document a clear founder signal in the Faroes and Iceland, but the strength of this signal is haplogroup-dependent which may be indicative of more recent admixture or other demographic processes. Discussion: The results of the current study and lack of conformity between Icelandic and Faroese haplotypes implies that the two populations were founded by different paternal gene pools and there is no detectable post-founder admixture between the two groups. [ABSTRACT FROM AUTHOR]

Introduction: Suicide is a major public health concern within the United States, and prevention efforts are essential for decreasing the suicide rate. Researchers and clinicians have knowledge and effective treatments for preventing suicide; however, their impact is limited to those with access to services. Science Communication (SciComm) is an effective tool that can be integrated into the field of suicide prevention and can bridge the gap between scientific findings and the general population. SciComm can help disseminate evidence‐based strategies for suicide prevention, dispel misinformation on suicide, and normalize help‐seeking. Purpose: In this article, we propose specific, tangible ways that SciComm can be integrated into graduate school programs, mentorship, career advancement requirements and can help enact systemic change within the field of suicide prevention. Additionally, we discuss why it is important that the field of suicide prevention, specifically, adopts a SciComm framework. Embracing SciComm can help the field of suicide prevention to have a broader impact and can help to reduce rates of suicide. [ABSTRACT FROM AUTHOR]

Background There is an increasing awareness that aging of the immune system, or immunosenescence, is a key biological process underlying many of the hallmark diseases of aging and age-related decline broadly. While immunosenescence can be in part due to normal age-related changes in the immune system, emerging evidence posits that viral infections may be biological stressors of the immune system that accelerate the pace of immunosenescence Methods We used a convenience sample of 42 individuals aged 65 years and older to examine correlations between antiviral immunoglobulin G (IgG) levels for 4 human herpesviruses (cytomegalovirus [CMV], herpes simplex virus [types 1 and 2], and Epstein-Barr virus) and multiple indicators of T-cell immunosenescence. Results We found that most of the sample (n = 33) was antiviral IgG positive for 2 or more of the 4 herpesvirus infections. We also examined correlations between both the total number of viruses for which an individual had antiviral IgG and each individual virus and multiple indicators of T-cell immunosenescence, particularly p16 expression. The strongest correlations were observed between the total number of viruses for which an individual had detectable antiviral IgG and p16 mean fluorescent intensity (MFI) among CD27-CD28-CD57+ CD4+ cells (r = 0.60; P <.001) and between anti-CMV IgG and p16 MFI of CD27-CD57+ CD4+ cells (r = 0.59; P <.001). Conclusions Broadly, our findings offer compelling preliminary evidence for future investigations to incorporate multiple indicators of persistent viral infections and a more comprehensive set of markers of T-cell immunosenescence in population-based studies of aging. [ABSTRACT FROM AUTHOR]

In humans and in mice, maternal allergy predisposes offspring to development of allergy. In murine models, increased levels of maternal β-glucosylceramides are both necessary and sufficient for the development of allergic predisposition in offspring. Furthermore, increased numbers of CD11b+ dendritic cell subsets in the offspring of allergic mothers are associated with allergic predisposition. In vitro, β-glucosylceramides increase CD11b+ dendritic cell subset numbers through increased PKCδ signaling, but it is not known if enhanced PKCδ signaling in dendritic cells is required in vivo. We demonstrate that dendritic cell–specific deletion of PKCδ prevents the β-glucosylceramide–induced increase in CD11b+ dendritic cell subset numbers both in vitro as well as in vivo in the fetal liver of offspring of mothers injected with β-glucosylceramides. Furthermore, dendritic cell–specific deletion of PKCδ in offspring prevents the maternal allergy–induced increase in CD11b+ dendritic cell subsets and decreases allergen-induced interleukin-5 and eosinophilia in lungs of offspring. However, loss of PKCδ in dendritic cells did not prevent development of allergen-specific IgE. Our study provides mechanistic insight into the function of PKCδ in the origins of allergic disease beginning in utero as well as in the development of postnatal allergic lung inflammation. [ABSTRACT FROM AUTHOR]

Objective To assess the health disparities across social determinants of health (SDoH) domains for the risk of severe acidosis independent of demographical and clinical factors. Materials and Methods A retrospective case-control study (n  = 13 310, 1:4 matching) is performed using electronic health records (EHRs), SDoH surveys, and genomics data from the All of Us participants. The propensity score matching controls confounding effects due to EHR data availability. Conditional logistic regressions are used to estimate odds ratios describing associations between SDoHs and the risk of acidosis events, adjusted for demographic features, and clinical conditions. Results Those with employer-provided insurance and those with Medicaid plans show dramatically different risks [adjusted odds ratio (AOR): 0.761 vs 1.41]. Low-income groups demonstrate higher risk (household income less than $25k, AOR: 1.3-1.57) than high-income groups ($100-$200k, AOR: 0.597-0.867). Other high-risk factors include impaired mobility (AOR: 1.32), unemployment (AOR: 1.32), renters (AOR: 1.41), other non-house-owners (AOR: 1.7), and house instability (AOR: 1.25). Education was negatively associated with acidosis risk. Discussion Our work provides real-world evidence of the comprehensive health disparities due to socioeconomic and behavioral contributors in a cohort enriched in minority groups or underrepresented populations. Conclusions SDoHs are strongly associated with systematic health disparities in the risk of severe metabolic acidosis. Types of health insurance, household income levels, housing status and stability, employment status, educational level, and mobility disability play significant roles after being adjusted for demographic features and clinical conditions. Comprehensive solutions are needed to improve equity in healthcare and reduce the risk of severe acidosis. [ABSTRACT FROM AUTHOR]

Background Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early mortality, we hypothesized that patients with SCD are experiencing accelerated biological aging compared with individuals without SCD. Methods We utilized the DunedinPACE measure to compare the epigenetic pace of aging in 131 Black Americans with SCD to 1391 Black American veterans without SCD. Results SCD patients displayed a significantly accelerated pace of aging (DunedinPACE mean difference of 0.057 points) compared with the veterans without SCD, whereby SCD patients were aging ≈0.7 months more per year than those without SCD (p  = 4.49 × 10−8). This was true, even though the SCD patients were significantly younger according to chronological age than the individuals without SCD, making the epigenetic aging discrepancy even more apparent. This association became stronger when we removed individuals with posttraumatic stress disorder from the non-SCD group (p  = 2.18 × 10−9), and stronger still when we restricted the SCD patients to those with hemoglobin SS and Sβ0 thalassemia genotypes (p  = 1.61 × 10−10). Conclusions These data support our hypothesis that individuals with SCD experience accelerated biological aging as measured by global epigenetic variation. The assessment of epigenetic measures of biological aging may prove useful to identify which SCD patients would most benefit from clinical interventions to reduce mortality. [ABSTRACT FROM AUTHOR]

Objective: Although child safety seats are highly effective in preventing injuries, they are frequently misused. Experts have identified two leading "critical misuses": (1) loose harness straps and (2) loose vehicle attachment at the base. We designed an innovative child safety seat system that educates, instructs, and alarms participants of safety seat errors. The system includes both the Cellular Car Seat (CCS) smartphone app and a network of car seat sensors. Our objective was to determine if CCS system users had fewer child safety seat misuses than users with a child safety seat manual alone. Methods: During the study visit, 92 participants completed three safety seat scenarios using a mock vehicle setup, test doll, and a convertible child safety seat: A) fully install a convertible safety seat, B) recognizing/correcting loose harness straps in a seat with intentionally loose straps, and C) recognizing/correcting loose attachment to the vehicle seat at the base in a seat with intentionally loose attachment. Intervention participants (n = 46) were asked to use the CCS app during each scenario and control participants (n = 46) were given only the paper child safety seat manual. For each scenario, researchers determined errors/misuses present at the end of the scenario, time to complete scenario, and tension achieved on the harness straps (collected via load cell). Results: Compared with controls, intervention participants had significantly fewer errors and higher average harness tensions for all three scenarios; furthermore, a greater portion achieved a harness tension of 4 newtons. During Scenario A, the rate of loose harness strap errors was more than three times higher for controls and loose base attachment errors almost six times higher. We observed similar trends in Scenario B, with harness strap errors more than double for controls. In Scenario C, the rates of both critical misuse errors were four times higher for controls compared to the intervention group. Conclusions: The innovative CCS system was highly effective at reducing child safety seat use errors, especially critical misuses. Reducing critical misuses will decrease injuries and fatalities among crash-involved children. The CCS system can alert families to everyday harnessing and installation errors and provide families and caregivers with ongoing, accessible support. [ABSTRACT FROM AUTHOR]

Ras homolog family member A (RhoA) acts as a signaling hub in many cellular processes, including cytoskeletal dynamics, division, migration, and adhesion. RhoA activity is tightly spatiotemporally controlled, but whether downstream effectors share these activation dynamics is unknown. We developed a novel single-color FRET biosensor to measure Rho-associated kinase (ROCK) activity with high spatiotemporal resolution in live cells. We report the validation of the Rho-Kinase Activity Reporter (RhoKAR) biosensor. RhoKAR activation was specific to ROCK activity and was insensitive to PKA activity. We then assessed the mechanisms of ROCK activation in mouse fibroblasts. Increasing intracellular calcium with ionomycin increased RhoKAR activity and depleting intracellular calcium with EGTA decreased RhoKAR activity. We also investigated the signaling intermediates in this process. Blocking calmodulin or CaMKII prevented calcium-dependent activation of ROCK. These results indicate that ROCK activity is increased by calcium in fibroblasts and that this activation occurs downstream of CaM/CaMKII. [ABSTRACT FROM AUTHOR]

Simple Summary: Intraoperative radiation therapy (IORT) can be a useful treatment modality in patients with recurrent cervical or endometrial cancer. The existing literature on IORT use in recurrent gynecologic malignancies is limited by small sample sizes because few centers use IORT and few patients are ideal candidates. The aim of our study is to describe a modern cohort of patients who were considered for IORT and predict risk factors of morbidity and mortality. We found that appreciable survival gain can be achieved with the use of IORT, with factors such as ECOG performance status (ECOG PS), neoadjuvant chemotherapy/immunotherapy, pelvic sidewall involvement, whether exenteration was performed, and resection margin status influencing the risk of morbidity and/or mortality. Background/Objectives: Our objective was to describe the use of intraoperative radiation therapy (IORT) for the treatment of recurrent/persistent cervical or endometrial cancer and assess predictors of postoperative complications and 3-year mortality. Methods: In this multi-site retrospective study, data were abstracted for recurrent/persistent endometrial or cervical cancer patients who underwent IORT from June 2004 to May 2021. Complications were graded on the six-point Accordion scale. Variables associated with complications were analyzed with univariate logistic regression, while variables associated with death within 3 years were analyzed with Cox proportional hazards modeling. Survival was analyzed with the Kaplan–Meier method. Results: Eighty patients had planned IORT for recurrent/persistent endometrial (n = 35) or cervical cancer (n = 45). The mean age of the cohort was 56.8 years (SD = 13.7), and the median disease-free interval from primary disease to recurrence was 20.0 months (IQR 10.0–63.1). The overall survival at 3 years was 48.6% (95% CI: 38.3–61.6%) with a median survival of 2.8 years. Within 30 days postoperative, 16 patients (20.1%) had grade 3–5 complications and one death (1.3%) occurred. Factors associated with grade 3+ complication included ECOG PS 2–3 (OR 18.00, p = 0.04), neoadjuvant chemotherapy and/or immunotherapy (OR 6.98, p < 0.01), and pelvic sidewall involvement (OR 8.80, p = 0.04). Factors associated with death within 3 years of surgery included ECOG PS 2–3 (HR 8.97, p < 0.01), neoadjuvant chemotherapy and/or immunotherapy (HR 2.34, p = 0.03), whether exenteration was performed (HR 2.64, p = 0.01), and positive resection margin (HR 3.37, p < 0.01). Conclusions: In well-selected patients, IORT is a feasible and safe option for the treatment of recurrent/persistent gynecologic malignancy with an appreciable survival benefit. [ABSTRACT FROM AUTHOR]

The ability to recognize and associate objects with prior experiences has been demonstrated in several avian taxa. Corvids, for example, recognize visual stimuli associated with negative previous experiences and will modify their behavioral responses according to the level of perceived threat. However, the extent to which similar memory-based behaviors exist in seabirds is poorly understood. Our study investigated object recognition by Herring Gulls ( Larus argentatus smithsonianus ) on their breeding grounds, the site of a long-term monitoring project. When handling gulls and conducting field research, researchers wear standard bicycle helmets as a protective measure against physical aggression by nesting gulls. We tested whether previously banded gulls vary their behavioral responses based on the headgear worn by human researchers. Herring Gulls were significantly more aggressive when approached by helmeted observers compared to those wearing neutral headwear or even holding a helmet, thus indicating a potential association between wearing bike helmets and the negative experience with researchers. Our study demonstrates that Herring Gulls are capable of object memory and object recognition within context, and display different behaviors toward different objects according to their levels of perceived threat. This information is key when designing studies with nesting gulls to ensure that behavioral biases are not unintentionally created due to gull prior experiences or researcher safety gear.

The effects of synthetic, free-amino acid diets, similar to those prescribed as supplements for (phenylketonuria) PKU patients, on gut microbiota and overall health are not well understood. In the current, multidisciplinary study, we examined the effects of a synthetically-derived, low-fiber, amino acid diet on behavior, cognition, gut microbiome composition, and inflammatory markers. A cohort of 20 male C57BL/6J mice were randomly assigned to either a standard or synthetic diet (n = 10) at post-natal day 21 and maintained for 13 weeks. Sequencing of the 16S rRNA gene from fecal samples revealed decreased bacterial diversity, increased abundance of bacteria associated with disease, such as Prevotella, and a downward shift in gut microbiota associated with fermentation pathways in the synthetic diet group. Furthermore, there were decreased levels of short chain fatty acids and shortening of the colon in mice consuming the synthetic diet. Finally, we measured TNF-α, IL-6, and IL-10 in serum, the hippocampus, and colon, and found that the synthetic diet significantly increased IL-6 production in the hippocampus. These results demonstrate the importance of a multidisciplinary approach to future diet and microbiome studies, as diet not only impacts the gut microbiome composition but potentially systemic health as well.

This qualitative descriptive study analyzed the role that natural mentors had in cultivating a sense of purpose and meaning among 38 diverse male and female high school students. The "types" of mentoring support provided and the students' perceived "experiences" of receiving the support were considered in the analysis. Directed content analysis revealed four initial overarching types of supportive actions that were provided by mentors: emotional, instrumental, informational, and appraisal support. The types of support offered were further categorized across three dimensions of perceived support by the mentees: (a) affirmation (e.g., the experience of emotional and appraisal support), (b) cultivation (e.g., the experience of being challenged and obtaining skills), and (c) guidance (e.g., the experience of receiving information and advice). In order for mentees to perceive and accept cultivation and guidance support, they first needed to experience an affirming relationship with their mentors. Findings may inform best practices for mentoring youth toward lives of meaning and purpose.

The Brain Trauma Foundation recommends intracranial pressure (ICP) monitor placement for patients with severe traumatic brain injury (TBI). Adherence with these guidelines in elderly patients is unknown. We hypothesized that disparities in ICP monitor placement would exist based on patient age.

Previously, a predictive model was developed to identify optimal blends of expensive high-quality and cheaper low-quality feedstocks for a given geographical location that can deliver high sugar yields. In this study, the optimal process conditions were tested for application at commercially-relevant higher biomass loadings. We observed lower sugar yields but 100% conversion to ethanol from a blend that contained only 20% high-quality feedstock. The impact of applying this predictive model simultaneously with least cost formulation model for a biorefinery location outside of the US Corn Belt in Lee County, Florida was investigated. A blend ratio of 0.30 EC, 0.45 SG, and 0.25 CS in Lee County was necessary to produce sugars at high yields and ethanol at a capacity of 50 MMGY. This work demonstrates utility in applying predictive model and LCF to reduce feedstock costs and supply chain risks while optimizing for product yields.

Eddy covariance measurements quantify the magnitude and temporal variability of land-atmosphere exchanges of water, heat, and carbon dioxide (CO2) among others. However, they also carry information regarding the influence of spatial heterogeneity within the flux footprint, the temporally dynamic source/sink area that contributes to the measured fluxes. A 25 m tall eddy covariance flux tower in Central Illinois, USA, a region where drastic seasonal land cover changes from intensive agriculture of maize and soybean occur, provides a unique setting to explore how the organized heterogeneity of row crop agriculture contributes to observations of land-atmosphere exchange. We characterize the effects of this heterogeneity on latent heat (LE), sensible heat (H), and CO2 fluxes (Fc) using a combined flux footprint and eco-hydrological modeling approach. We estimate the relative contribution of each crop type resulting from the structured spatial organization of the land cover to the observed fluxes from April 2016 to April 2019. We present the concept of a fetch rose, which represents the frequency of the location and length of the prevalent upwind distance contributing to the observations. The combined action of hydroclimatological drivers and land cover heterogeneity within the dynamic flux footprint explain interannual flux variations. We find that smaller flux footprints associated with unstable conditions are more likely to be dominated by a single crop type, but both crops typically influence any given flux measurement. Meanwhile, our ecohydrological modeling suggests that land cover heterogeneity leads to a greater than 10% difference in flux magnitudes for most time windows relative to an assumption of equally distributed crop types. This study shows how the observed flux magnitudes and variability depend on the organized land cover heterogeneity and is extensible to other intensively managed or otherwise heterogeneous landscapes.

Suicidal ideation (SI) often precedes and predicts suicide attempt and death, is the most common suicidal phenotype and is over-represented in veterans. The genetic architecture of SI in the absence of suicide attempt (SA) is unknown, yet believed to have distinct and overlapping risk with other suicidal behaviors. We performed the first GWAS of SI without SA in the Million Veteran Program (MVP), identifying 99,814 SI cases from electronic health records without a history of SA or suicide death (SD) and 512,567 controls without SI, SA or SD. GWAS was performed separately in the four largest ancestry groups, controlling for sex, age and genetic substructure. Ancestry-specific results were combined via meta-analysis to identify pan-ancestry loci. Four genome-wide significant (GWS) loci were identified in the pan-ancestry meta-analysis with loci on chromosomes 6 and 9 associated with suicide attempt in an independent sample. Pan-ancestry gene-based analysis identified GWS associations with DRD2, DCC, FBXL19, BCL7C, CTF1, ANNK1, and EXD3. Gene-set analysis implicated synaptic and startle response pathways (q's

Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset.

Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.

To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type-specific dynamics. We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C, SATB2, SOX5, TCF4, and TSHZ3) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.

Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms. We integrated genetic and genomic data to perform a transcriptome-wide association study, prioritizing disease loci likely mediated by cis effects on brain expression. This transcriptome-wide characterization of the molecular pathology across three major psychiatric disorders provides a comprehensive resource for mechanistic insight and therapeutic development.

ObjectiveThe objective of the study is to evaluate the association of intergenerational educational attainment with cardiovascular disease (CVD) risk factors among US Latinos.MethodsWe used cross-sectional data from the Niños Lifestyle and Diabetes Study, an offspring cohort of middle-aged Mexican-Americans whose parents participated in the Sacramento Latino Study on Aging. We collected educational attainment, demographic and health behaviours and measured systolic blood pressure (SBP), fasting glucose and waist circumference. We evaluated the association of parental, offspring and a combined parent-offspring education variable with each CVD risk factor using multivariable regression.ResultsHigher parental education was associated only with smaller offspring waist circumference. In contrast, higher offspring education was associated with lower SBP, fasting glucose and smaller waist circumference. Adjustment for parental health behaviours modestly attenuated these offspring associations, whereas adjustment for offspring health behaviours and income attenuated the associations of offspring education with offspring SBP and fasting glucose but not smaller waist circumference, even among offspring with low parental education.ConclusionsHigher offspring education is associated with lower levels of CVD risk factors in adulthood, despite intergenerational exposure to low parental education.