The function of serine/threonine-specific protein kinases in B cells.

The serine/threonine-specific protein kinases (STKs) are important for cell survival, proliferation, differentiation, and apoptosis. In B cells, these kinases play indispensable roles in regulating important cellular functions. Multiple studies on human and other animal cells have shown that multiple STKs are involved in different stages of B cell development and antibody production. However, how STKs affect B cell development and function is still not completely understood. Considering that B cells are clinically important in immunity and diseases, our understanding of STKs' roles in B cells is in great need of investigation with current technologies. Investigating serine/threonine kinases will not only deepen our insight into B cell-related disorders but also facilitate the identification of more effective drug targets for conditions like lymphoma and systemic lupus erythematosus.

Diet Quality and Eating Frequency Were Associated with Insulin-Taking Status among Adults.

OBJECTIVE: This pilot cross-sectional study explored differences in dietary intake and eating behaviors between healthy adults and a group of adults taking insulin to manage diabetes. METHODS: A characteristic questionnaire and up to four Automated Self-Administered 24-Hour dietary recalls were collected from 152 adults aged 18-65 years (96 healthy and 56 adults taking insulin) from Indiana and across the U.S. from 2022 to 2023. The macronutrient intake, diet quality via the Healthy Eating Index (HEI)-2015, eating frequency, and consistency of timing of eating were calculated and compared between the two groups using adjusted linear or logistic regression models. RESULTS: The total mean HEI scores were very low, at 56 out of 100 and 49 out of 100 for the healthy and insulin-taking groups, respectively. Insulin-taking adults had significantly lower HEI total (p = 0.003) and component scores compared to the healthy group for greens and beans (2.0 vs. 3.0, p = 0.02), whole fruit (2.1 vs. 2.9, p = 0.05), seafood and plant proteins (2.1 vs. 3.3, p = 0.004), and saturated fats (3.7 vs. 5.4, p = 0.05). Eating frequency was significantly lower in the insulin-taking group than in the healthy group (3.0 vs. 3.4 eating occasions/day, p = 0.05). CONCLUSION: Evidence of the low diet quality and eating frequency of insulin takers may help inform and justify nutrition education to control and manage diabetes.

Impact of incident rheumatoid arthritis on earnings: a nationwide sibling comparison study.

OBJECTIVES: RA is known to impact work ability but much of this knowledge comes from historical comparisons vs the general population that neither reflects current RA management, nor distinguishes between effects of RA and pre-existing socio-economic conditions of patients. We therefore aimed to examine earnings of patients before and after RA diagnosis, using recent data and sibling comparisons. METHODS: Swedish register data were used including demographic information and healthcare utilization. Participants were patients with RA (aged 30-60 years, diagnosed with RA 2006-2017) identified in the Swedish National Patient Register, and their same-sex siblings (n = 2433:2433; mean 48 y; 72% women). Earnings data for 2001-2019 were retrieved from Statistics Sweden and analysed from 5 years before to 5 years after RA diagnosis. RESULTS: No differences in average earnings were observed between siblings during the 5 years before diagnosis, but during the 5 years after diagnosis, patients with RA earned on average 5.4% less annually (-1430€[95%CI -2130, -720]) than same-sexed siblings. The change in earnings for the subgroup diagnosed 2006-2010 was -8.2% (-2020€[95%CI -2930, -1120]) but for patients diagnosed 2011-2017 there was no statistically significant change in earnings compared with siblings (-1.5%; -420€[95%CI -1490, 640]). Subgroup analyses demonstrated a more negative impact on earnings for older individuals and those with lower education level. CONCLUSION: RA diagnosis was associated with lower earnings in comparison with same-sex siblings, particularly for older individuals and those with lower education level. The negative impact of RA on earnings declined or disappeared over the study period.

Novel anti-virulence compounds disrupt exotoxin expression in MRSA.

Hemolysins are lytic exotoxins expressed in most strains of S. aureus, but hemolytic activity varies between strains. We have previously reported several novel anti-virulence compounds that disrupt the S. aureus transcriptome, including hemolysin gene expression. This report delves further into our two lead compounds, loratadine and a structurally related brominated carbazole, and their effects on hemolysin production in methicillin-resistant S. aureus (MRSA). To gain understanding into how these compounds affect hemolysis, we analyzed these exotoxins at the DNA, RNA, and protein level after in vitro treatment. While lysis of red blood cells varied between strains, DNA sequence variation did not account for it. We hypothesized that our compounds would modulate gene expression of multiple hemolysins in two hospital-acquired strains of MRSA, both with staphylococcal cassette chromosome mec (SCCmec) type II. RNA-seq analysis of differential gene expression in untreated and compound-treated cultures revealed hundreds of differentially expressed genes, with a significant enrichment in genes involved in hemolysis. The brominated carbazole and loratadine both displayed the ability to reduce hemolysis in strain 43300 but displayed differential activity in strain USA100. These results corroborate gene expression studies as well as western blots of alpha hemolysin. Together, this work suggests that small molecules may alter exotoxin production in MRSA but that the directionality and/or magnitude of the difference are likely strain dependent.IMPORTANCEMethicillin-resistant S. aureus (MRSA) is a deadly human pathogen. In addition to evading antibiotics, these bacteria produce a wide range of toxins that negatively affect the host. Our work aims to identify and characterize novel compounds that can decrease the pathogenic effects of MRSA. Two lead compounds investigated in this study triggered changes in the production of multiple toxins. These changes were specific to the strain of MRSA investigated. Specifically, this work sheds light on novel compounds that decrease MRSA's ability to lyse host red blood cells. Importantly, it also highlights the importance of examining strain-specific differences in response to therapeutic interventions that could ultimately affect clinical outcomes.

Dedicator of cytokinesis 8 (DOCK8) mutation impairs the differentiation of helper T cells by regulating the glycolytic pathway of CD4+ T cells.

Dedicator of cytokinesis 8 (DOCK8) deficiency is a primary immunodeficiency disease caused by mutations in exon 45 of the DOCK8 gene. The clinical signs primarily consist of increased serum IgE levels, eczema, repeated skin infections, allergies, and upper respiratory tract infections. Using CRISPR/Cas9 technology, we generated a DOCK8 exon 45 mutation in mice, mirroring the mutation found in patients. The results indicated that DOCK8 mutation impairs peripheral T cell homeostasis, disrupts regulatory T cells (Tregs) development, increases ICOS expression in Tregs within peripheral lymph nodes (pLn), and promotes Th17 cell differentiation within the spleen and pLn. Upon virus infection, DOCK8 mutation CD4+ T cells have a Th2 effector fate. RNA-bulk sequencing data revealed alternations in the mTOR pathway of DOCK8 mutant CD4+ T cells. We observed that DOCK8 mutation upregulates the glycolysis levels in CD4+ T cells, which is related to the Akt/mTOR/S6/HIF-1α pathway. In summary, our research elucidates that DOCK8 regulates the differentiation of helper T cells by modulating the glycolytic pathway in CD4+ T cells, thereby advancing the comprehension and offering potential treatment of diseases in DOCK8-deficient patients.

The interaction of innate immune and adaptive immune system.

The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll-like receptors to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific and sustained killing of pathogens via B cells, T cells, and antibodies. Traditionally, it has been assumed that innate immunity activates adaptive immunity; however, recent studies have revealed more complex interactions. This review provides a detailed dissection of the composition and function of the innate and adaptive immune systems, emphasizing their synergistic roles in physiological and pathological contexts, providing new insights into the link between these two forms of immunity. Precise regulation of both immune systems at the same time is more beneficial in the fight against immune-related diseases, for example, the cGAS-STING pathway has been found to play an important role in infections and cancers. In addition, this paper summarizes the challenges and future directions in the field of immunity, including the latest single-cell sequencing technologies, CAR-T cell therapy, and immune checkpoint inhibitors. By summarizing these developments, this review aims to enhance our understanding of the complexity interactions between innate and adaptive immunity and provides new perspectives in understanding the immune system.

Eating Egg-Rich Diets and Modeling the Addition of One Daily Egg Reduced Risk of Nutrient Inadequacy among United States Adolescents with and without Food Insecurity.

BACKGROUND: Adolescents have the poorest dietary intake throughout their lifespan. Food insecurity worsens these nutritional risks. Eggs are a nutrient-dense strategy to increase nutrient quality. OBJECTIVES: 1) compare usual nutrient intakes, Dietary Reference Intake and protein compliance with recommendations and scores of micronutrient quality; and 2) analyze how adding 1 egg affects adolescents' nutrient profiles, by food security status and egg-rich diets. METHODS: Dietary data of United States adolescents in the 2007-2018 National Health and Nutrition Examination Survey were analyzed (14-17 y; n = 3633). Egg-rich diet levels were categorized as 1) no eggs, 2) eggs as ingredients in dishes, or 3) primarily egg dishes. Food security status was classified using the United States Household Food Security Survey Module. The National Cancer Institute method was used to estimate usual nutrient intake and nutrient exposure scores [i.e., Food Nutrient Index (FNI) and Total Nutrient Index (TNI)]. Nutrient amounts from 1 medium egg were modeled on existing intakes. Pairwise t-tests determined significant differences. RESULTS: Over 60% of adolescents risked inadequate intake of calcium, choline, magnesium, vitamin D, and vitamin E regardless of food security status. Food-secure adolescents consuming primarily egg dishes had higher mean usual intakes of lutein + zeaxanthin (1544.1 µg), choline (408.4 mg), vitamin B2 (2.3 mg), selenium (128.6 µg), vitamin D (6 µg), docosahexaenoic acid (70 mg), and protein (89.1 g) than other groups (P < 0.0002). Those who were food secure and consuming eggs as ingredients in dishes demonstrated higher nutrient adequacy for magnesium (scored ∼66 out of 100), potassium (scored 81), and total scores (scored 72 and 69, respectively) for the TNI and FNI; and folate only (scored 92) for the TNI, than those who were food insecure and not consuming eggs (P < 0.0002). Adding 1 egg increased choline and vitamin D usual intakes for some groups and nutrient index scores for all groups (P < 0.0005). CONCLUSIONS: Adolescents are at substantial nutritional risk that was exacerbated by food insecurity and less egg consumption.

Diet Quality of Community Café Meals Among Guests With Food Insecurity.

OBJECTIVE: Compare the diet quality of a meal consumed at a community café (café meals), a pay-what-you-can restaurant, to a meal consumed for an equivalent eating occasion on the day before (comparison meal) by guests with food insecurity. METHODS: Dietary recalls were collected from café guests with food insecurity to determine the Healthy Eating Index-2020 (HEI-2020) total and component scores. Healthy Eating Index-2020 scores were compared between meals using paired-sample t tests and Wilcoxon signed-rank tests. RESULTS: Most participants (n = 40; 80% male; 42.5% Black) had very low food security (70.0%). Café meal had a higher HEI-2020 total score (46.7 ± 10.5 vs 34.4 ± 11.6; P < 0.001) and total vegetables (2.6 ± 2.0 vs 1.2 ± 1.7; P = 0.004), total fruits (2.1 ± 2.2 vs 0.6 ± 1.5; P < 0.001), whole fruits (1.6 ± 2.0 vs 0.3 ± 0.9; P < 0.001), and refined grains (7.8 ± 3.5 vs 3.9 ± 3.9; P < 0.001) scores than comparison meals. CONCLUSIONS AND IMPLICATIONS: The café meal had better diet quality than the comparison meal, suggesting its potential for improving diet quality among guests with food insecurity.

Analytic Methods for Understanding the Temporal Patterning of Dietary and 24-H Movement Behaviors: A Scoping Review.

Dietary and movement behaviors [physical activity (PA), sedentary behavior (SED), and sleep] occur throughout a 24-h day and involve multiple contexts. Understanding the temporal patterning of these 24-h behaviors and their contextual determinants is key to determining their combined effect on health. A scoping review was conducted to identify novel analytic methods for determining temporal behavior patterns and their contextual correlates. We searched Embase, ProQuest, and EBSCOhost databases in July 2022 to identify studies published between 1997 and 2022 on temporal patterns and their contextual correlates (e.g., locational, social, environmental, personal). We included 14 studies after title and abstract (n = 33,292) and full-text (n = 135) screening, of which 11 were published after 2018. Most studies (n = 4 in adults; n = 5 in children and adolescents), examined waking behavior patterns (i.e., both PA and SED) of which 3 also included sleep and 6 included contextual correlates. PA and diet were examined together in only 1 study of adults. Contextual correlates of dietary, PA, and sleep temporal behavior patterns were also examined. Machine learning with various clustering algorithms and model-based clustering techniques were most used to determine 24-h temporal behavior patterns. Although the included studies used a diverse range of methods, behavioral variables, and assessment periods, results showed that temporal patterns characterized by high SED and low PA were linked to poorer health outcomes, than those with low SED and high PA. This review identified temporal behavior patterns, and their contextual correlates, which were associated with adiposity and cardiometabolic disease risk, suggesting these methods hold promise for the discovery of holistic lifestyle exposures important to health. Standardized reporting of methods and patterns and multidisciplinary collaboration among nutrition, PA, and sleep researchers; statisticians; and computer scientists were identified as key pathways to advance future research on temporal behavior patterns in relation to health.

Bullying Victimization and Adverse Childhood Experiences: Retrospective Reports of Relative Impact on Emotional Distress.

The literature suggests that there is a significant overlap in definition, measurement, and outcomes between trauma and bullying victimization, but the relative impact on current emotional distress of these events has not been explored. The goal of the current study was to explore whether traditional and cyber bullying victimization has a similar negative impact on current emotional disrtresss as other adverse childhood experiences which may also lead to a traumatic response. In addition, this study examined whether the association between bullying victimization and emotional distress is exacerbated when individuals also experience additional ACEs. Retrospective reports from a diverse sample of 576 adults were collected via an online survey. When ranked against other ACEs such as viewing family mental health problems or substance abuse, or verbal, physical, emotional, and sexual victimization not from peers, nearly 30% of participants ranked bullying victimization as having the most negative impact on their levels of emotional distress. Multi-group path analyses indicated that experiencing additional ACEs seems to exacerbate distress caused by bullying and cyber bullying victimization. The current study suggests that bullying victimization may be just as detrimental as other types of ACEs that occur in childhood.

Novel Anti-virulence Compounds Disrupt Exotoxin Expression in MRSA.

Hemolysins are lytic exotoxins expressed in most strains of S. aureus , but hemolytic activity varies between strains. We have previously reported several novel anti-virulence compounds that disrupt the S. aureus transcriptome, including hemolysin gene expression. This report delves further into our two lead compounds, loratadine and a structurally related brominated carbazole, and their effects on hemolysin production in MRSA. To gain understanding into how these compounds affect hemolysis, we analyzed these exotoxins at the DNA, RNA, and protein level after in vitro treatment. While lysis of red blood cells varied between strains, DNA sequence variation did not account for it. We hypothesized that our compounds would modulate gene expression of multiple hemolysins in a laboratory strain and a clinically relevant hospital-acquired strain of MRSA, both with SCC mec type II. RNA-seq analysis of differential gene expression in untreated and compound-treated cultures revealed hundreds of differentially expressed genes, with a significant enrichment in genes involved in hemolysis. The brominated carbazole and loratadine both displayed the ability to reduce hemolysis in the laboratory strain, but displayed differential activity in a hospital-acquired strain. These results corroborate gene expression studies as well as western blots of alpha hemolysin. Together, this work suggests that small molecules may alter exotoxin production in MRSA, but that the directionality and/or magnitude of the difference is likely strain-dependent.

Corrigendum: A community focused approach toward making healthy and affordable daily diet recommendations.

[This corrects the article DOI: 10.3389/fdata.2023.1086212.].

Expression of USP25 associates with fibrosis, inflammation and metabolism changes in IgG4-related disease.

IgG4-related disease (IgG4-RD) has complex clinical manifestations ranging from fibrosis and inflammation to deregulated metabolism. The molecular mechanisms underpinning these phenotypes are unclear. In this study, by using IgG4-RD patient peripheral blood mononuclear cells (PBMCs), IgG4-RD cell lines and Usp25 knockout mice, we show that ubiquitin-specific protease 25 (USP25) engages in multiple pathways to regulate fibrotic and inflammatory pathways that are characteristic to IgG4-RD. Reduced USP25 expression in IgG4-RD leads to increased SMAD3 activation, which contributes to fibrosis and induces inflammation through the IL-1ß inflammatory axis. Mechanistically, USP25 prevents ubiquitination of RAC1, thus, downregulation of USP25 leads to ubiquitination and degradation of RAC1. Decreased RAC1 levels result in reduced aldolase A release from the actin cytoskeleton, which then lowers glycolysis. The expression of LYN, a component of the B cell receptor signalosome is also reduced in USP25-deficient B cells, which might result in B cell activation deficiency. Altogether, our results indicate a potential anti-inflammatory and anti-fibrotic role for USP25 and make USP25 a promising diagnostic marker and potential therapeutic target in IgG4-RD.

The role of the community café in addressing food security: Perceptions of managers and directors.

In the United States, the pay-what-you-can restaurant model (community cafes) is an increasingly popular approach to addressing food insecurity in local communities. We conducted semi-structured interviews (n = 13) with community café executive managers and directors to assess their perceptions of the role that their cafes play in addressing food security (FS). Analysis of interviews revealed two major areas of emphasis by participants. Filling an unoccupied space in the food security landscape. Interviewees regularly cited the goal of making meals available through a dependable schedule, convenient location, and welcoming atmosphere for guests to promote regular visits to the café, and they did so with an awareness of how their practices were shaped by perceived shortcomings in comparable services. In addition, guest agency and social aspects of the café as components of utilization, was another major area. Interviewees often regarded the opportunity of the food insecure guest to choose healthy options (i.e., nutritionally dense) over less healthful ones (i.e., calorically dense) from the menu as a critical component of their service. The social component of the café (e.g., community atmosphere, 'dining-out' experience) was another aspect of the café's function that promoted dignity for the guest which can lead to greater likelihood of return visits. Perceptions shared by participants of the café's role in addressing food security suggest that rather than simply adding to the available options of hunger relief services, the café model attempts to address many areas of concern, such as structural and cultural barriers, found in the traditional forms of charitable food provision.

Workshop summary: building an NHANES for the future.

The American Society for Nutrition's (ASN) Committee on Advocacy and Science Policy (CASP) organized a workshop, "Building a National Health and Nutrition Examination Survey (NHANES) for the Future," held during NUTRITION 2023, which took place in Boston, MA in July 2023. CASP had already identified an urgent need for increased support and modernization to ensure that a secure future for NHANES is achievable. The survey faces challenges associated with data collection, stagnant funding, and a need for more granular data for subpopulations and groups at risk. The workshop provided an overview of NHANES, including the nutrition component, and the many other uses for the survey's data, which extend beyond nutrition. Speakers highlighted NHANES's current and emerging challenges, as well as possible solutions to address these challenges, especially with regard to response rates of underrepresented groups, linkage of survey data to other resources, incorporation of new survey methodologies, and emerging data needs. The workshop also included a "Town Hall" component to gather additional feedback on NHANES' challenges and proposed solutions from audience members. The workshop provided many possible action items that ASN will explore and use to inform effective continued advocacy in support of NHANES and to find possible opportunities for ASN and others to partner with the Centers for Disease Control and Prevention National Center for Health Statistics to strengthen this vital survey and maintain its robust and relevant data moving forward.

The characterization of CD8+ T-cell responses in COVID-19.

This review gives an overview of the protective role of CD8+ T cells in SARS-CoV-2 infection. The cross-reactive responses intermediated by CD8+ T cells in unexposed cohorts are described. Additionally, the relevance of resident CD8+ T cells in the upper and lower airway during infection and CD8+ T-cell responses following vaccination are discussed, including recent worrisome breakthrough infections and variants of concerns (VOCs). Lastly, we explain the correlation between CD8+ T cells and COVID-19 severity. This review aids in a deeper comprehension of the association between CD8+ T cells and SARS-CoV-2 and broadens a vision for future exploration.

Loratadine Combats Methicillin-Resistant Staphylococcus aureus by Modulating Virulence, Antibiotic Resistance, and Biofilm Genes.

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved to become resistant to multiple classes of antibiotics. New antibiotics are costly to develop and deploy, and they have a limited effective lifespan. Antibiotic adjuvants are molecules that potentiate existing antibiotics through nontoxic mechanisms. We previously reported that loratadine, the active ingredient in Claritin, potentiates multiple cell-wall active antibiotics in vitro and disrupts biofilm formation through a hypothesized inhibition of the master regulatory kinase Stk1. Loratadine and oxacillin combined repressed the expression of key antibiotic resistance genes in the bla and mec operons. We hypothesized that additional genes involved in antibiotic resistance, biofilm formation, and other cellular pathways would be modulated when looking transcriptome-wide. To test this, we used RNA-seq to quantify transcript levels and found significant effects in gene expression, including genes controlling virulence, antibiotic resistance, metabolism, transcription (core RNA polymerase subunits and sigma factors), and translation (a plethora of genes encoding ribosomal proteins and elongation factor Tu). We further demonstrated the impacts of these transcriptional effects by investigating loratadine treatment on intracellular ATP levels, persister formation, and biofilm formation and morphology. Loratadine minimized biofilm formation in vitro and enhanced the survival of infected Caenorhabditis elegans. These pleiotropic effects and their demonstrated outcomes on MRSA virulence and survival phenotypes position loratadine as an attractive anti-infective against MRSA.

Dietary Intakes of Community-Dwelling Adults in the United States across Older Adulthood: National Health and Nutrition Examination Survey 2015-March 2020.

BACKGROUND: Dietary guidance is set on the basis of age and life stage and defines older adults as ≥60 y. Yet, little is known about if and/or how diet quality differs beyond the age of 60. OBJECTIVE: The objective of this study was to compare the dietary intakes of 60-69 (n = 2079), 70-79 (n = 1181), and 80+ y old (n = 644) noninstitutionalized men and women in the United States using the Healthy Eating Index 2015 (HEI) and the What We Eat in America food categories. METHODS: Data were obtained from National Health and Nutrition Examination Survey 2015-2016 and 2017-March 2020. HEI and component scores were calculated using the population ratio method. Population estimates for dietary intake were calculated as the average reported over 2 separate nonconsecutive 24-h dietary recalls. RESULTS: In men and women, the reported energy intake was lower among the 80+ y olds (kcal/d men-80+: 1884 ± 30, 70-79: 2022 ± 33, 60-69: 2142 ± 39; women-80+: 1523 ± 36; 70-79: 1525 ± 33, 60-69: 1650 ± 25; P-trend < 0.001). Total HEI scores did not differ significantly across the 3 age categories, but the 80+ y olds had significantly lower scores for the green vegetables and beans component than the 60-69 y olds [men-mean (95% confidence interval): 2.0 (1.5, 2.5) compared with 3.4 (2.6, 4.1); women-2.3 (1.8, 2.8) compared with 4.4 (3.7, 5.0)]. In women, the percentage of daily calories from protein was significantly lower in the 80+ y olds than in the 60-69 and 70-79 y olds (12.9% ± 0.6%, compared with 17.0% ± 0.9% and 15.6% ± 0.6%, respectively). Protein intake did not differ significantly among the 3 age groups in men. The 80+ y old men and women reported consuming a significantly higher percentage of calories from snacks and sweets compared with the 60-69 y olds (men-80+: 18.1% ± 0.8%, 60-69: 15.4% ± 0.7%; women-80+: 19.6% ± 0.8%, 60-69: 15.5% ± 0.7%). CONCLUSION: The diet of 80+ y olds differed from that of 60-69 y olds in some key components, including energy, snacks and sweets, protein, and green vegetables. Future research is needed to determine if there are health-related consequences to these differences.

Temporal Dietary Pattern Cluster Membership Varies on Weekdays and Weekends but Both Link to Health.

BACKGROUND: Energy and dietary quality are known to differ between weekdays and weekends. Data-driven approaches that incorporate time, amount, and duration of dietary intake have previously been used to partition participants' daily weekday dietary intake time series into clusters representing weekday temporal dietary patterns (TDPs) linked to health indicators in United States adults. Yet, neither the relationship of weekend day TDPs to health indicators nor how the TDP membership may change from weekday to weekend is known. OBJECTIVES: This study was conducted to determine the association between TDPs on weekdays and weekend days and health indicators [diet quality, waist circumference (WC), body mass index (BMI), and obesity] and their overlap among participants. METHODS: A weekday and weekend day 24-hour dietary recall of 9494 nonpregnant United States adults aged 20-65 years from the cross-sectional National Health and Nutrition Examination Survey 2007-2018 was used to determine the timing and amount of energy intake. Modified dynamic time warping and kernel k-means algorithm clustered participants into 4 TDPs on weekdays and weekend days. Multivariate regression models determined the associations between TDPs and health indicators, controlling for potential confounders and adjusting for the survey design and multiple comparisons. The percentages of overlap in cluster membership between TDPs on weekdays and weekend days were also determined. RESULTS: United States adults with a TDP of evenly spaced, energy-balanced eating occasions, representing the TDP of more than one-third of all adults on weekdays and weekends, had significantly higher diet quality, lower BMI, WC, and odds of obesity when compared to those with other TDPs. Membership of most United States adults to TDPs varied from weekdays to weekends. CONCLUSIONS: Both weekday and weekend TDPs were significantly associated with health indicators. TDP membership of most United States adults was not consistent on weekdays and weekends.

OvaPrint-A Cell-free DNA Methylation Liquid Biopsy for the Risk Assessment of High-grade Serous Ovarian Cancer.

PURPOSE: High-grade serous ovarian carcinoma (HGSOC) is the most lethal epithelial ovarian cancer (EOC) and is often diagnosed at late stage. In women with a known pelvic mass, surgery followed by pathologic assessment is the most reliable way to diagnose EOC and there are still no effective screening tools in asymptomatic women. In the current study, we developed a cell-free DNA (cfDNA) methylation liquid biopsy for the risk assessment of early-stage HGSOC. EXPERIMENTAL DESIGN: We performed reduced representation bisulfite sequencing to identify differentially methylated regions (DMR) between HGSOC and normal ovarian and fallopian tube tissue. Next, we performed hybridization probe capture for 1,677 DMRs and constructed a classifier (OvaPrint) on an independent set of cfDNA samples to discriminate HGSOC from benign masses. We also analyzed a series of non-HGSOC EOC, including low-grade and borderline samples to assess the generalizability of OvaPrint. A total of 372 samples (tissue n = 59, plasma n = 313) were analyzed in this study. RESULTS: OvaPrint achieved a positive predictive value of 95% and a negative predictive value of 88% for discriminating HGSOC from benign masses, surpassing other commercial tests. OvaPrint was less sensitive for non-HGSOC EOC, albeit it may have potential utility for identifying low-grade and borderline tumors with higher malignant potential. CONCLUSIONS: OvaPrint is a highly sensitive and specific test that can be used for the risk assessment of HGSOC in symptomatic women. Prospective studies are warranted to validate OvaPrint for HGSOC and further develop it for non-HGSOC EOC histotypes in both symptomatic and asymptomatic women with adnexal masses.