The Landscape of Care for Women Veterans with Cancer: An Evidence Map.

BACKGROUND: Women are the fastest growing veteran group in the US and the number of women veterans (WVs) with cancer is rising; however, little is known about this population. Cancer care for WVs is complex and it is essential to understand their unique needs and care coordination challenges to provide evidence-based care. The purpose of this review is to map the quantity, distribution, and characteristics of literature describing cancer and its treatment among WVs. METHODS: We searched MEDLINE (via PubMed), Embase (Elsevier), and Web of Science Core Collection (Clarivate) from inception through January, 2024. Publications were eligible that reported gender-specific data on any aspect of cancer care among WVs. Data was abstracted by a single investigator with over-reading. RESULTS: Forty-six reports were included; 44 were observational and 19 had a women-only sample. There were no interventional reports and no qualitative reports had a patient sample. Breast cancer was the most commonly addressed (n = 19). There were six additional reports on sex-specific cancers. Many reports used large VA databases or previous trial data, creating the potential for patient overlap between reports. Among VA-specific areas of interest, only three reports evaluated the potential implications of racial differences and only two included a transgender population. No reports examined the effects of toxic exposures on cancer. Within the NCI Cancer Control Continuum, crosscutting areas were more commonly represented; over half (25) of the reports addressed epidemiology. There were few reports on focus areas and little overlap between focus and crosscutting areas. DISCUSSION: Existing literature provides an inadequate understanding of the population of WVs with cancer. There is scant information regarding the population of WVs with cancer, their care preferences or experiences, or how to best identify and address unmet healthcare needs. It is imperative to expand research to provide evidence-based care for this population.

PCBS: an R package for fast and accurate analysis of bisulfite sequencing data.

Motivation: Whole-genome bisulfite sequencing is a powerful tool for analyzing chromatin methylation genome-wide, but analysis of whole-genome bisulfite data is hampered by slow, inaccurate, and inflexible pipelines. Results: We developed PCBS, a computationally efficient R package for Whole Genome Bisulfite Sequencing analysis that demonstrates remarkable accuracy and flexibility compared to current tools. PCBS identifies differentially methylated loci and differentially methylated regions and offers novel functionality that allows for more targeted methylation analyses. PCBS uses minimal computational resources; a complete pipeline in mouse can run on a local RStudio instance in a matter of minutes. Availability and Implementation: PCBS is an R package available under a GNU GPLv3 license at: https://github.com/katlande/PCBS and from CRAN: https://CRAN.R-project.org/package=PCBS. Instructions for use are available at: https://katlande.github.io/PCBS/.

Electroconvulsive therapy for the acute management of severe agitation in dementia (ECT-AD): A modified study protocol.

OBJECTIVE: This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented. METHODS: Initially, the RCT randomized participants 1:1 to either ECT plus usual care or simulated ECT plus usual care (S-ECT) groups. As patients were enrolled, data were collected from both ECT and simulated ECT (S-ECT) patients. The study now continues in an open-label study design where all patients receive actual ECT, reducing the targeted sample size from 200 to 50 participants. RESULTS: Study is ongoing and open to enrollment. CONCLUSION: The transition of the ECT-AD study design from an RCT to open-label design exemplifies adaptive research methodologies in response to real-world challenges. Data from both the RCT and open-label phases of the study will provide a unique perspective on the role of ECT in managing severe treatment-refractory agitation in dementia, potentially influencing future clinical practices and research approaches.

Morphological diversification and functional maturation of human astrocytes in glia-enriched cortical organoid transplanted in mouse brain.

Astrocytes, the most abundant glial cell type in the brain, are underrepresented in traditional cortical organoid models due to the delayed onset of cortical gliogenesis. Here we introduce a new glia-enriched cortical organoid model that exhibits accelerated astrogliogenesis. We demonstrated that induction of a gliogenic switch in a subset of progenitors enabled the rapid derivation of astroglial cells, which account for 25-31% of the cell population within 8-10 weeks of differentiation. Intracerebral transplantation of these organoids reliably generated a diverse repertoire of cortical neurons and anatomical subclasses of human astrocytes. Spatial transcriptome profiling identified layer-specific expression patterns among distinct subclasses of astrocytes within organoid transplants. Using an in vivo acute neuroinflammation model, we identified a subpopulation of astrocytes that rapidly activates pro-inflammatory pathways upon cytokine stimulation. Additionally, we demonstrated that CD38 signaling has a crucial role in mediating metabolic and mitochondrial stress in reactive astrocytes. This model provides a robust platform for investigating human astrocyte function.

NGLY1 mutations cause protein aggregation in human neurons.

Biallelic mutations in the gene that encodes the enzyme N-glycanase 1 (NGLY1) cause a rare disease with multi-symptomatic features including developmental delay, intellectual disability, neuropathy, and seizures. NGLY1's activity in human neural cells is currently not well understood. To understand how NGLY1 gene loss leads to the specific phenotypes of NGLY1 deficiency, we employed direct conversion of NGLY1 patient-derived induced pluripotent stem cells (iPSCs) to functional cortical neurons. Transcriptomic, proteomic, and functional studies of iPSC-derived neurons lacking NGLY1 function revealed several major cellular processes that were altered, including protein aggregate-clearing functionality, mitochondrial homeostasis, and synaptic dysfunctions. These phenotypes were rescued by introduction of a functional NGLY1 gene and were observed in iPSC-derived mature neurons but not astrocytes. Finally, laser capture microscopy followed by mass spectrometry provided detailed characterization of the composition of protein aggregates specific to NGLY1-deficient neurons. Future studies will harness this knowledge for therapeutic development.

Associations between blood pressure control and clinical events suggestive of nutrition care documented in electronic health records of patients with hypertension.

BACKGROUND: Clinical events suggestive of nutrition care found in electronic health records (EHRs) are rarely explored for their associations with hypertension outcomes. METHODS: Longitudinal analysis using structured EHR data from primary care visits at a health system in the US from December 2017-December 2020 of adult patients with hypertension (n = 4,237) tested for associations between last visit blood pressure (BP) control (≤ 140 Systolic BP and ≤ 90 Diastolic BP) and ≥ 1 nutrition care clinical event operationalized as (overweight or obesity (BMI > 25 or 30, respectively) diagnoses, preventive care visits, or provision of patient education materials (PEM)). Descriptive statistics and longitudinal targeted maximum likelihood estimation (LTMLE) models were conducted to explore average treatment effects (ATE) of timing and dose response from these clinical events on blood pressure control overall and by race. RESULTS: The median age was 62 years, 29% were male, 52% were Black, 25% were from rural areas and 50% had controlled BP at baseline. Annual documentation of overweight/obesity diagnoses ranged 3.0-7.8%, preventive care visits ranged 6.2-15.7%, and PEM with dietary and hypertension content were distributed to 8.5-28.8% patients. LTMLE models stratified by race showed differences in timing, dose, and type of nutrition care. Black patients who had nutrition care in Year 3 only compared to none had lower odds for BP control (ATE -0.23, 95% CI: -0.38,-0.08, p = 0.003), preventive visits in the last 2 years high higher odds for BP control (ATE 0.31, 95% CI: 0.07,0.54, p = 0.01), and early or late PEMs had lower odds for BP control (ATE -0.08, 95% CI: -0.15,-0.01, p = 0.03 and ATE -0.23, 95% CI: -0.41,-0.05, p = 0.01, respectively). CONCLUSIONS: In this study, clinical events suggestive of nutrition care are significantly associated with BP control, but are infrequent and effects differ by type, timing, and patient race. Preventive visits appear to have the most effect; additional research should include examining clinical notes for evidence of nutrition care among different populations, which may uncover areas for improving nutrition care for patients with chronic disease.

Associations between Blood Pressure Control and Documented Nutrition Care Using Structured Data from Electronic Health Records of Patients with Hypertension.

Background: Documentation in Electronic Health Records (EHRs) of nutrition care events (overweight or obesity (BMI > 25 or 30, respectively) diagnoses, preventive care visits, or provision of patient education materials (PEM)) for chronic diseases is unclear. Methods: Cross-sectional analysis using structured EHR data from primary care visits at a health system in the US from January 2018 - December 2020 of adult patients with hypertension (n = 6,419) tested for associations between last visit blood pressure (BP) control (≤ 140 Systolic BP and ≤ 90 Diastolic BP) and aggregate nutrition care events. Descriptive statistics and multiple logistic regression models were constructed to examine the predictive power of nutrition care events for blood pressure control. Results: The median age was 62 years, 32% were male, 48% were Black, 26% were from rural areas and 35.9% had controlled BP at last visit. For the 62% of patients with documented nutrition care, 14.6% had an overweight/obesity diagnosis, 26.2% had a preventive care visit, and 42% received PEM with dietary and hypertension content. The models showed patients who had more preventive care visits (aOR 1.12; CL 1.06, 1.18) had higher odds for BP control. Whereas Black patients compared with white patients (aOR 0.84; CL 0.74, 0.95), those with more hypertension medications (aOR 0.97; CL 0.96, 0.99) and more primary care visits over the study period (aOR 0.98; CL 0.97, 0.99) had lower odds for BP control. Conclusions: In this study, documented nutrition care in preventive care visits is significantly associated with BP control, but documentation is infrequent. Additional research should include examining clinical notes for evidence of nutrition care, which may uncover areas that show promise for improving nutrition care for patients with chronic disease.

Age-dependent roles of cardiac remodeling in sepsis defense and pathogenesis.

Disease tolerance is a defense strategy essential for survival of infections, limiting physiological damage without killing the pathogen. The disease course and pathology a pathogen may cause can change over the lifespan of a host due to the structural and functional physiological changes that accumulate with age. Since successful disease tolerance responses require the host to engage mechanisms that are compatible with the disease course and pathology caused by an infection, we predicted that this defense strategy would change with age. Animals infected with a lethal dose 50 (LD50) of a pathogen often display distinct health and sickness trajectories due to differences in disease tolerance, and thus can be used to delineate tolerance mechanisms. Using a polymicrobial sepsis model, we found that despite having the same LD50, old and young susceptible mice exhibited distinct disease courses. Young survivors employed a cardioprotective mechanism via FoxO1-mediated regulation of the ubiquitin-proteosome system that was necessary for survival and protection from cardiomegaly. This same mechanism was a driver of sepsis pathogenesis in aged hosts, causing catabolic remodeling of the heart and death. Our findings have implications for the tailoring of therapy to the age of an infected individual and suggest that disease tolerance alleles may exhibit antagonistic pleiotropy.

Transgenerational inheritance of acquired epigenetic signatures at CpG islands in mice.

Transgenerational epigenetic inheritance in mammals remains a debated subject. Here, we demonstrate that DNA methylation of promoter-associated CpG islands (CGIs) can be transmitted from parents to their offspring in mice. We generated DNA methylation-edited mouse embryonic stem cells (ESCs), in which CGIs of two metabolism-related genes, the Ankyrin repeat domain 26 and the low-density lipoprotein receptor, were specifically methylated and silenced. DNA methylation-edited mice generated by microinjection of the methylated ESCs exhibited abnormal metabolic phenotypes. Acquired methylation of the targeted CGI and the phenotypic traits were maintained and transmitted across multiple generations. The heritable CGI methylation was subjected to reprogramming in parental PGCs and subsequently reestablished in the next generation at post-implantation stages. These observations provide a concrete step toward demonstrating transgenerational epigenetic inheritance in mammals, which may have implications in our understanding of evolutionary biology as well as the etiology, diagnosis, and prevention of non-genetically inherited human diseases.

Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis.

Cancers arise through the accumulation of genetic and epigenetic alterations that enable cells to evade telomere-based proliferative barriers and achieve immortality. One such barrier is replicative crisis-an autophagy-dependent program that eliminates checkpoint-deficient cells with unstable telomeres and other cancer-relevant chromosomal aberrations1,2. However, little is known about the molecular events that regulate the onset of this important tumour-suppressive barrier. Here we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as a regulator of the crisis program. A crisis-associated isoform of ZBP1 is induced by the cGAS-STING DNA-sensing pathway, but reaches full activation only when associated with telomeric-repeat-containing RNA (TERRA) transcripts that are synthesized from dysfunctional telomeres. TERRA-bound ZBP1 oligomerizes into filaments on the outer mitochondrial membrane of a subset of mitochondria, where it activates the innate immune adapter protein mitochondrial antiviral-signalling protein (MAVS). We propose that these oligomerization properties of ZBP1 serve as a signal amplification mechanism, where few TERRA-ZBP1 interactions are sufficient to launch a detrimental MAVS-dependent interferon response. Our study reveals a mechanism for telomere-mediated tumour suppression, whereby dysfunctional telomeres activate innate immune responses through mitochondrial TERRA-ZBP1 complexes to eliminate cells destined for neoplastic transformation.

Multiomics atlas-assisted discovery of transcription factors enables specific cell state programming.

The same types of cells can assume diverse states with varying functionalities. Effective cell therapy can be achieved by specifically driving a desirable cell state, which requires the elucidation of key transcription factors (TFs). Here, we integrated epigenomic and transcriptomic data at the systems level to identify TFs that define different CD8 + T cell states in an unbiased manner. These TF profiles can be used for cell state programming that aims to maximize the therapeutic potential of T cells. For example, T cells can be programmed to avoid a terminal exhaustion state (Tex Term ), a dysfunctional T cell state that is often found in tumors or chronic infections. However, Tex Term exhibits high similarity with the beneficial tissue-resident memory T states (T RM ) in terms of their locations and transcription profiles. Our bioinformatic analysis predicted Zscan20 , a novel TF, to be uniquely active in Tex Term . Consistently, Zscan20 knock-out thwarted the differentiation of Tex Term in vivo , but not that of T RM . Furthermore, perturbation of Zscan20 programs T cells into an effector-like state that confers superior tumor and virus control and synergizes with immune checkpoint therapy. We also identified Jdp2 and Nfil3 as powerful Tex Term drivers. In short, our multiomics-based approach discovered novel TFs that enhance anti-tumor immunity, and enable highly effective cell state programming. One sentence summary: Multiomics atlas enables the systematic identification of cell-state specifying transcription factors for therapeutic cell state programming.

Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals.

Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention that involves a daily cycle of feeding and fasting. In both animals and humans, TRF has pleiotropic health benefits that arise from multiple organ systems, yet the molecular basis of TRF-mediated benefits is not well understood. Here, we subjected mice to isocaloric ad libitum feeding (ALF) or TRF of a western diet and examined gene expression changes in samples taken from 22 organs and brain regions collected every 2 h over a 24-h period. We discovered that TRF profoundly impacts gene expression. Nearly 80% of all genes show differential expression or rhythmicity under TRF in at least one tissue. Functional annotation of these changes revealed tissue- and pathway-specific impacts of TRF. These findings and resources provide a critical foundation for future mechanistic studies and will help to guide human time-restricted eating (TRE) interventions to treat various disease conditions with or without pharmacotherapies.

Comparison of Inpatient Standard-of-Care to Outpatient Oritavancin Therapy for Patients With Acute Uncomplicated Cellulitis.

BACKGROUND: Shifting inpatient antibiotic treatment to outpatient parenteral antimicrobial therapy may minimize treatment for acute bacterial skin and skin structure infections, including cellulitis. The purpose of this evaluation was to compare 30-day hospital readmission or admission due to cellulitis and economic outcomes of inpatient standard-of-care (SoC) management of acute uncomplicated cellulitis to outpatient oritavancin therapy. METHODS: This retrospective, observational cohort study was conducted at a 941-bed community teaching hospital. Adult patients 18 years and older treated for acute uncomplicated cellulitis between February 2015 to December 2018 were eligible for inclusion. Information was obtained from hospital and billing department records. Patients were assigned to either inpatient SoC or outpatient oritavancin cohorts for comparison. RESULTS: 1,549 patients were included in the study (1,348 in the inpatient SoC cohort and 201 in the outpatient oritavancin cohort). The average length of stay for patients admitted was 3.6 ± 1.5 days. The primary outcome of 30-day hospital readmission or admission due to cellulitis occurred in 49/1348 (3.6%) patients in the inpatient SoC cohort versus 1/201 (0.5%) in the outpatient oritavancin cohort (p = 0.02). The difference between costs and reimbursement was improved in the outpatient oritavancin group (p < 0.001). CONCLUSION: Outpatient oritavancin for acute uncomplicated cellulitis was associated with reduction in 30-day hospital readmissions or admissions compared to inpatient SoC. Beneficial economic outcomes for the outpatient oritavancin cohort were observed. Additional studies are required to confirm these findings.

Design and execution of sham-controlled endoscopic trials in acute pancreatitis: Lessons learned from the SHARP trial.

Using the ongoing NIDDK-funded multicenter randomized clinical trial, Sphincterotomy for Acute Recurrent Pancreatitis (SHARP) as an example, this article discusses the rationale and key aspects of study design that need to be considered when conducting a clinical trial of endoscopic therapy in acute pancreatitis. SHARP, the first trial using a sham ERCP in the placebo group, is designed to address a decades long controversy in clinical pancreatology, i.e. whether minor papilla sphincterotomy benefits patients with idiopathic acute recurrent pancreatitis who also have pancreas divisum. Although the trial has already enrolled and randomized over 5 times the number of subjects enrolled in the only randomized trial in this area published in 1992 (107 vs. 19), recruitment has been challenging and we are at ∼46% of target recruitment. The review discusses the challenges in the execution of the trial and strategies the SHARP team has used to address these, which investigators planning or considering treatment trials in pancreatitis may find helpful. It will also inform the general gastroenterologists the importance of discussing and referring potentially eligible subjects to centers participating in clinical trials. Developing evidence-based treatment will provide a solid scientific basis for physicians to recommend evidence-based treatments for pancreatitis.

Time-restricted eating alters the 24-hour profile of adipose tissue transcriptome in men with obesity.

OBJECTIVE: Time-restricted eating (TRE) restores circadian rhythms in mice, but the evidence to support this in humans is limited. The objective of this study was to investigate the effects of TRE on 24-hour profiles of plasma metabolites, glucoregulatory hormones, and the subcutaneous adipose tissue (SAT) transcriptome in humans. METHODS: Men (n = 15, age = 63 [4] years, BMI 30.5 [2.4] kg/m2 ) were recruited. A 35-hour metabolic ward stay was conducted at baseline and after 8 weeks of 10-hour TRE. Assessment included 24-hour profiles of plasma glucose, nonesterified fatty acid (NEFA), triglyceride, glucoregulatory hormones, and the SAT transcriptome. Dim light melatonin onset and cortisol area under the curve were calculated. RESULTS: TRE did not alter dim light melatonin onset but reduced morning cortisol area under the curve. TRE altered 24-hour profiles of insulin, NEFA, triglyceride, and glucose-dependent insulinotropic peptide and increased transcripts of circadian locomotor output cycles protein kaput (CLOCK) and nuclear receptor subfamily 1 group D member 2 (NR1D2) and decreased period circadian regulator 1 (PER1) and nuclear receptor subfamily 1 group D member 1 (NR1D1) at 12:00 am. The rhythmicity of 450 genes was altered by TRE, which enriched in transcripts for transcription corepressor activity, DNA-binding transcription factor binding, regulation of chromatin organization, and small GTPase binding pathways. Weighted gene coexpression network analysis revealed eigengenes that were correlated with BMI, insulin, and NEFA. CONCLUSIONS: TRE restored 24-hour profiles in hormones, metabolites, and genes controlling transcriptional regulation in SAT, which could underpin its metabolic health benefit.

SNPs, short tandem repeats, and structural variants are responsible for differential gene expression across C57BL/6 and C57BL/10 substrains.

Mouse substrains are an invaluable model for understanding disease. We compared C57BL/6J, which is the most commonly used inbred mouse strain, with eight C57BL/6 and five C57BL/10 closely related inbred substrains. Whole-genome sequencing and RNA-sequencing analysis yielded 352,631 SNPs, 109,096 indels, 150,344 short tandem repeats (STRs), 3,425 structural variants (SVs), and 2,826 differentially expressed genes (DE genes) among these 14 strains; 312,981 SNPs (89%) distinguished the B6 and B10 lineages. These SNPs were clustered into 28 short segments that are likely due to introgressed haplotypes rather than new mutations. Outside of these introgressed regions, we identified 53 SVs, protein-truncating SNPs, and frameshifting indels that were associated with DE genes. Our results can be used for both forward and reverse genetic approaches and illustrate how introgression and mutational processes give rise to differences among these widely used inbred substrains.

Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies.

Sprague Dawley (SD) rats are among the most widely used outbred laboratory rat populations. Despite this, the genetic characteristics of SD rats have not been clearly described, and SD rats are rarely used for experiments aimed at exploring genotype-phenotype relationships. In order to use SD rats to perform a genome-wide association study (GWAS), we collected behavioral data from 4,625 SD rats that were predominantly obtained from two commercial vendors, Charles River Laboratories and Harlan Sprague Dawley Inc. Using double-digest genotyping-by-sequencing (ddGBS), we obtained dense, high-quality genotypes at 291,438 SNPs across 4,061 rats. This genetic data allowed us to characterize the variation present in Charles River vs. Harlan SD rats. We found that the two populations are highly diverged (FST > 0.4). Furthermore, even for rats obtained from the same vendor, there was strong population structure across breeding facilities and even between rooms at the same facility. We performed multiple separate GWAS by fitting a linear mixed model that accounted for population structure and using meta-analysis to jointly analyze all cohorts. Our study examined Pavlovian conditioned approach (PavCA) behavior, which assesses the propensity for rats to attribute incentive salience to reward-associated cues. We identified 46 significant associations for the various metrics used to define PavCA. The surprising degree of population structure among SD rats from different sources has important implications for their use in both genetic and non-genetic studies.

Are primary care providers' nutrition care and food insecurity screening practices associated with their perceptions of team-based care?

BACKGROUND: Screening for food insecurity (FI) and providing nutrition care are important management strategies for chronic diseases, but rates are low. Aspects of team-based care and providers' nutrition competence may help inform interventions to improve these services. The objectives of this study were to describe US primary care providers' FI screening and nutrition care practices (counselling, referrals, and time spent counselling) and test for associations with scored measures of their perceptions of team-based care (care continuity, patient-centredness, coordination with external providers and resources) and nutrition competence (confidence counselling and attitudes towards nutrition). METHODS: Cross-sectional online survey data of primary care providers were described and analysed for associations using Wilcoxon rank sum tests. RESULTS: Of provider respondents (N = 92), 35% (n = 32) worked in clinics that screen for FI and had higher team perceptions (P = 0.006) versus those who do not. Those who reported counselling >30% patients about nutrition (57%, n = 52) and referring >10% patients to nutrition professionals (24%, n = 22) had significantly better attitudes towards nutrition (P = 0.013 and P = 0.04, respectively) compared with those with lower counselling and referral rates. Half (n = 46) of the providers reported spending >3-min counselling each patient about nutrition and had higher patient-centred care (P = 0.004) and nutrition competence (P < 0.001) compared with those who spent less time counselling. CONCLUSION: Providers in clinics that screen for FI had higher overall perceptions of team-based care, but their nutrition competence was not significantly different. Meanwhile, reported more time counselling was associated with a culture of patient-centredness. Promoting team-based care may be a mechanism for improving FI screening and nutrition care.

Time-restricted eating improves glycemic control and dampens energy-consuming pathways in human adipose tissue.

OBJECTIVE: We sought to examine the effects of 8 wk of time-restricted eating (TRE) on glucose metabolism and the adipose tissue transcriptome during a metabolic ward stay in men with obesity. METHODS: In a single-arm, pre-post trial, 15 men (ages 63 ± 4 y, body mass index = 30.5 ± 2.4 kg/m2, waist circumference = 113 ± 4 cm) with obesity but no history of diabetes were enrolled and underwent 2 wk of baseline monitoring before they were instructed to eat their regular diets within a contiguous 10-h time frame each day for 8 wk. Metabolic testing was performed at baseline and week 8 during a 35-h metabolic ward stay, during which all food intake was strictly timed and controlled. Identical meal-tolerance tests were performed at breakfast and dinner. Blood glucose, glucoregulatory hormones, and subjective appetite score were measured. Subcutaneous adipose tissue biopsies were performed and the transcriptome was assessed. RESULTS: The primary outcome, plasma glucose area under the curve, was altered by TRE, being unchanged at breakfast but increased at dinner. However, TRE reduced fasting glucose, glycated hemoglobin, body weight, and body fat, and increased glucose-dependent insulinotropic peptide area under the curve at dinner. In subcutaneous adipose tissue, 117 genes were up-regulated and 202 genes down-regulated by TRE. Pathway analysis revealed down-regulation of genes involved in proteasome function and mitochondrial regulation. CONCLUSIONS: TRE had a net effect of reducing glycemia and dampening energy-consuming pathways in adipose tissue.

Engaging rural communities in cancer prevention and control research: Development and preliminary insights from a community-based research registry.

OBJECTIVE: To report on the development and preliminary findings of a community-based cancer registry, including the community-engaged approach to recruitment, participant profile, and distribution of cancer risk factors by race/ethnicity and geography. METHODS: Community outreach and engagement best practices were used to recruit a diverse convenience sample of Virginia residents (≥18 years) that oversampled residents living in rural areas, defined as Rural-Urban Continuum Codes (RUCC) 4-9 and African American (AA)/Black residents. Multiple survey administration methods included electronic (e-survey) and in-person survey by community-based staff. RESULTS: At the time of this analysis, 595 participants are enrolled; 73% are rural, 46% are AA/Black. AA/Black participants reported similar education but lower income (p < 0.01) and health literacy (p < 0.01), lower alcohol use (p < 0.001), fewer sedentary behaviors (p = 0.01), but greater BMI (p < 0.05) compared to White participants. Rural residents reported significantly lower household income (p < 0.001) and greater use of Medicaid (p = 0.01) compared to urban participants. Biennial mammography was reported by 82% of women aged 45-74 years old and colonoscopy by 77% of participants ≥50 years old. Tobacco use was reported by 17%; no differences in cancer screening or tobacco use were identified by geography or by race. CONCLUSION AND RELEVANCE: Community engagement strategies successfully enrolled diverse residents within the cancer service area. AA/Black participants reported fewer cancer risk behaviors, similar educational attainment but lower income and health literacy compared to White respondents. Nuanced examinations of interactions among multilevel factors are needed to understand how individual, community, and institutional factors converge to maintain cancer disparities among AA/Black Virginians. Additional findings indicate a need for tobacco cessation, lung cancer screening, obesity treatment, and prevention initiatives.