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BackgroundUnderstanding the distinct immunologic responses to SARS-CoV-2 infection among pediatric populations is pivotal in navigating the COVID-19 pandemic and informing future public health strategies. This study aimed to identify factors associated with heightened antibody responses in children and adolescents to identify potential unique immune dynamics in this population.MethodsData collected between July and December 2023 from the Texas Coronavirus Antibody REsponse Survey (Texas CARES), a statewide prospective population-based antibody survey among 1-to-19-year-old participants, were analyzed. Each participant had the following data available for analysis: (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for Nucleocapsid protein antibodies (Roche N-test), (2) qualitative and semi-quantitative detection of antibodies to the SARS CoV-2 spike protein receptor binding domain (Roche S-test), and (3) self-reported antigen/PCR COVID-19 test results, vaccination, and health status. Statistical analysis identified associations between participant characteristics and spike antibody quartile group.ResultsThe analytical sample consisted of 411 participants (mean age 12.2 years, 50.6% female). Spike antibody values ranged from a low of 6.3 U/ml in the lowest quartile to a maximum of 203,132.0 U/ml in the highest quartile in the aggregate sample. Older age at test date (OR = 1.22, 95% CI: 1.12, 1.35, p

BackgroundOlder cancer survivors likely experience physical function limitations due to cancer and its treatments, leading to disability and early mortality. Existing studies have focused on factors associated with surgical complications and mortality risk rather than factors associated with the development of poor disability status (DS), a proxy measure of poor performance status, in cancer survivors. We aimed to identify factors associated with the development of poor DS among older survivors of colorectal cancer (CRC) and compare poor DS rates to an age-sex-matched, non-cancer cohort.MethodsThis retrospective cohort study utilized administrative data from the Texas Cancer Registry Medicare-linked database. The study cohort consisted of 13,229 survivors of CRC diagnosed between 2005 and 2013 and an age-sex-matched, non-cancer cohort of 13,225 beneficiaries. The primary outcome was poor DS, determined by Davidoff’s method, using predictors from 12 months of Medicare claims after cancer diagnosis. Multivariable Cox proportional hazards regression was used to identify risk factors associated with the development of poor DS.ResultsAmong the survivors of CRC, 97% were 65 years or older. After a 9-year follow-up, 54% of survivors of CRC developed poor DS. Significant factors associated with future poor DS included: age at diagnosis (hazard ratio [HR] = 3.50 for >80 years old), female sex (HR = 1.50), race/ethnicity (HR = 1.34 for Hispanic and 1.21 for Black), stage at diagnosis (HR = 2.26 for distant metastasis), comorbidity index (HR = 2.18 for >1), and radiation therapy (HR = 1.21). Having cancer (HR = 1.07) was significantly associated with developing poor DS in the pooled cohorts; age and race/ethnicity were also significant factors.ConclusionsOur findings suggest that a CRC diagnosis is independently associated with a small increase in the risk of developing poor DS after accounting for other known factors. The study identified risk factors for developing poor DS in CRC survivors, including Hispanic and Black race/ethnicity, age, sex, histologic stage, and comorbidities. These findings underscore the importance of consistent physical function assessments, particularly among subsets of older survivors of CRC who are at higher risk of disability, to prevent developing poor DS.

Summary: Background: Squamous cell carcinoma of the anus (SCCA) annual incidence among sexual minority men with and without HIV is 85/100,000 and 19/100,000 persons, respectively, which is significantly higher than the overall incidence (2/100,000). Incidence may also be higher in transgender women. Since SCCA tumours average ≥30 mm at diagnosis, we assessed the accuracy of individuals to self-detect smaller anal abnormalities. Methods: Using convenience sampling, the study enrolled sexual minority men and transgender women, aged 25–81 years, in Chicago, Illinois and Houston, Texas, USA, during 2020–2022. Individuals were taught the anal self-examination and anal companion examination (ASE/ACE). Then, a clinician performed a digital anal rectal examination (DARE) before participants conducted the ASE or ACE. The sensitivity, specificity and concordance of the ASE/ACE to detect an abnormality were measured along with factors associated with ASE/ACE and DARE concordance. Findings: Among 714 enrolled individuals, the median age was 40 years (interquartile range, 32–54), 36.8% (259/703) were living with HIV, and 47.0% (334/710), 23.4% (166/710), and 23.0% (163/710) were non-Hispanic white, non-Hispanic Black, and Hispanic, respectively. A total of 94.1% (671/713) identified as cisgendered men, and 5.9% (42/713) as gender minorities. A total of 658 participants completed an ASE and 28 couples (56 partners) completed an ACE. Clinicians detected abnormalities in 34.3% (245/714) of individuals. The abnormalities were a median of 3 mm in diameter. Sensitivity and specificity of the ASE/ACE was 59.6% (95% CI 53.5–65.7%) and 80.2% (95% CI 76.6–83.8%), respectively. Overall concordance was 0.73 (95% CI 0.70–0.76) between ASE/ACE and DARE and increased with increasing anal canal lesion size (p = 0.02). Concordance was lower when participants were older and received ASE/ACE training from a lay person rather than a clinician. Interpretation: Sexual minority men/transgender women may self-detect SCCA when malignant lesions are much smaller than the current mean dimension at presentation of ≥30 mm. Funding: National Cancer Institute.

Evidence suggests that individuals diagnosed with Parkinson’s Disease (PD) spend less time in moderate-to-vigorous intensity physical activity (MVPA) compared to those without PD. However, prior studies primarily included men and did not consider movement across the entire intensity spectrum. To address these gaps, the association of PD status with total volume physical activity and time spent in sedentary, low light-intensity physical activity (LLPA), high light-intensity physical activity (HLPA), and MVPA among older women was examined. This is a cross-sectional analysis of 17,466 ambulatory women enrolled in the Women’s Health Study (WHS) with a median (IQR) age of 70 (67–75) years who were asked to wear an accelerometer for 7 days from 2011 to 2015 for the ancillary study. Reported PD status was assessed via annual mail-in questionnaires prior to device wear. Compared to those without PD (n = 16,661), PD (n = 80) was associated with 98,400 fewer vector magnitude (VM) counts per day and with spending an average of 23.2 more minutes per day sedentary and 10.5 more minutes per day in LLPA. Further, PD was associated with spending 6.4 and 27.3 fewer minutes per day in HLPA and MVPA, respectively, compared to women without PD. PD in women is associated with more daily sedentary time and less time spent in health-enhancing physical activity. Prevention strategies to promote physical activity should be emphasized to enhance health and limit progression of disability in women living with PD.

Objective: To describe COVID-19 illness characteristics, risk factors, and SARS-CoV-2 serostatus by variant time period in a large community-based pediatric sample. Design: Data were collected prospectively over four timepoints between October 2020 and November 2022 from a population-based cohort ages 5 to 19 years old. Setting: State of Texas, USA. Participants: Participants ages 5 to 19 years were recruited from large pediatric healthcare systems, Federally Qualified Healthcare Centers, urban and rural clinical practices, health insurance providers, and a social media campaign. Exposure: SARS-CoV-2 infection. Main Outcome(s) and Measure(s): SARS-CoV-2 antibody status was assessed by the Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test). Self-reported antigen or PCR COVID-19 test results and symptom status were also collected. Results: Over half (57.2%) of the sample (N = 3911) was antibody positive. Symptomatic infection increased over time from 47.09% during the pre-Delta variant time period, to 76.95% during Delta, to 84.73% during Omicron, and to 94.79% during the Omicron BA.2. Those who were not vaccinated were more likely (OR 1.71, 95% CI 1.47, 2.00) to be infected versus those fully vaccinated. Conclusions: Results show an increase in symptomatic COVID-19 infection among non-hospitalized children with each progressive variant over the past two years. Findings here support the public health guidance that eligible children should remain up to date with COVID-19 vaccinations.

Accurate estimates of natural and/or vaccine-induced antibodies to SARS-CoV-2 are difficult to obtain. Although model-based estimates of seroprevalence have been proposed, they require inputting unknown parameters including viral reproduction number, longevity of immune response, and other dynamic factors. In contrast to a model-based approach, the current study presents a data-driven detailed statistical procedure for estimating total seroprevalence (defined as antibodies from natural infection or from full vaccination) in a region using prospectively collected serological data and state-level vaccination data. Specifically, we conducted a longitudinal statewide serological survey with 88,605 participants 5 years or older with 3 prospective blood draws beginning September 30, 2020. Along with state vaccination data, as of October 31, 2021, the estimated percentage of those 5 years or older with naturally occurring antibodies to SARS-CoV-2 in Texas is 35.0% (95% CI = (33.1%, 36.9%)). This is 3× higher than, state-confirmed COVID-19 cases (11.83%) for all ages. The percentage with naturally occurring or vaccine-induced antibodies (total seroprevalence) is 77.42%. This methodology is integral to pandemic preparedness as accurate estimates of seroprevalence can inform policy-making decisions relevant to SARS-CoV-2.

The COVID-19 pandemic impacted the conduct of in-person physical activity (PA) interventions among older survivors of BC, who need such interventions to stay active and prevent functional decline. We tested the feasibility of virtually delivering an exergame-based PA intervention to older BC survivors. We enrolled 20 female BC survivors ≥55 years and randomly assigned them to two groups. The intervention group (Pink Warrior 2) received 12 weekly virtual exergame sessions with behavioral coaching, survivorship navigation support, and a Fitbit for self-monitoring. The control group received 12 weekly phone-based survivorship discussion sessions and wore a Mi Band 3. Feasibility was evaluated by rates of recruitment (≥0.92 participants/center/month), retention (≥80%), and group attendance (≥10 sessions), percentage of completed virtual assessments, and number of technology-related issues and adverse events. Intervention acceptability was measured by participants’ ratings on a scale of 1 (strongly disagree) to 5 (strongly agree). The recruitment rate was 1.93. The retention and attendance rates were 90% and 88% (≥10 sessions), respectively. Ninety-six percent completed virtual assessments without an adverse event. Acceptability was high (≥4). The intervention met benchmarks for feasibility. Additional research is needed to further understand the impact of virtually delivered PA interventions on older BC survivors.

Abstract Background CpG Island Methylator Phenotype (CIMP) is an epigenetic phenotype in CRC characterized by hypermethylation of CpG islands in promoter regions of tumor suppressor genes, leading to their transcriptional silencing and loss of function. While the prevalence of CRC differs across geographical regions, no studies have compared prevalence of CIMP-High phenotype across regions. The purpose of this project was to compare the prevalence of CIMP across geographical regions after adjusting for variations in methodologies to measure CIMP in a meta-analysis. Methods We searched PubMed, Medline, and Embase for articles focusing on CIMP published from 2000 to 2018. Two reviewers independently identified 111 articles to be included in final meta-analysis. We classified methods used to quantify CIMP into 4 categories: a) Classical (MINT marker) Panel group b) Weisenberg-Ogino (W-O) group c) Human Methylation Arrays group and d) Miscellaneous group. We compared the prevalence of CIMP across geographical regions after correcting for methodological variations using meta-regression techniques. Results The pooled prevalence of CIMP-High across all studies was 22% (95% confidence interval:21–24%; I2 = 94.75%). Pooled prevalence of CIMP-H across Asia, Australia, Europe, North America and South America was 22, 21, 21, 27 and 25%, respectively. Meta-regression analysis identified no significant differences in the prevalence of CIMP-H across geographical regions after correction for methodological variations. In exploratory analysis, we observed variations in CIMP-H prevalence across countries. Conclusion Although no differences were found for CIMP-H prevalence across countries, further studies are needed to compare the influence of demographic, lifestyle and environmental factors in relation to the prevalence of CIMP across geographical regions.

Abstract Background Studies suggest that right ventricular (RV) fibrosis is associated with RV remodeling and long-term outcomes in patients with tetralogy of Fallot (TOF). Pre-operative hypoxia may increase expression of hypoxia inducible factor-1-alpha (HIF1α) and promote transforming growth factor β1 (TGFβ1)-mediated fibrosis. We hypothesized that there would be associations between: (1) RV fibrosis and RV function, (2) HIF1α variants and RV fibrosis, and (3) HIF1α variants and RV function among post-surgical TOF cases. Methods We retrospectively measured post-surgical fibrotic load (indexed volume and fibrotic score) from 237 TOF cases who had existing cardiovascular magnetic resonance imaging using late gadolinium enhancement (LGE), and indicators of RV remodeling (i.e., ejection fraction [RVEF] and end-diastolic volume indexed [RVEDVI]). Genetic data were available in 125 cases. Analyses were conducted using multivariable linear mixed-effects regression with a random intercept and multivariable generalized Poisson regression with a random intercept. Results Indexed fibrotic volume and fibrotic score significantly decreased RVEF by 1.6% (p = 0.04) and 0.9% (p = 0.03), respectively. Indexed fibrotic volume and score were not associated with RVEDVI. After adjusting for multiple comparisons, 6 of the 48 HIF1α polymorphisms (representing two unique signals) were associated with fibrotic score. None of the HIF1α polymorphisms were associated with indexed fibrotic volume, RVEDVI, or RVEF. Conclusion The association of some HIF1α polymorphisms and fibrotic score suggests that HIF1α may modulate the fibrotic response in TOF.

The sudden onset of the coronavirus (SARS-CoV-2) pandemic has resulted in tremendous loss of human life and economy in more than 210 countries and territories around the world. While self-protections such as wearing masks, sheltering in place, and quarantine policies and strategies are necessary for containing virus transmission, tens of millions of people in the U.S. have lost their jobs due to the shutdown of businesses. Therefore, how to reopen the economy safely while the virus is still circulating in population has become a problem of significant concern and importance to elected leaders and business executives. In this study, mathematical modeling is employed to quantify the profit generation and the infection risk simultaneously from a business entity's perspective. Specifically, an ordinary differential equation model was developed to characterize disease transmission and infection risk. An algebraic equation is proposed to determine the net profit that a business entity can generate after reopening and take into account the costs associated of several protection/quarantine guidelines. All model parameters were calibrated based on various data and information sources. Sensitivity analyses and case studies were performed to illustrate the use of the model in practice. The results show that with a combination of necessary infection protection measures implemented, a business entity may stand a good opportunity to generate a positive net profit while successfully controlling the within-business infection prevalence under that in the general population. The use of personal protective equipment (PPE) is also found of significant importance, especially at the early stage of business reopening.

BACKGROUND: CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations. However, other factors potentially associated with CIMP have not been robustly examined. This meta-analysis provides a comprehensive assessment of the clinical, pathologic, and molecular characteristics that define CIMP tumors. METHODS: We conducted a comprehensive search of the literature from January 1999 through April 2018 and identified 122 articles, on which comprehensive data abstraction was performed on the clinical, pathologic, molecular, and mutational characteristics of CIMP subgroups, classified based on the extent of DNA methylation of tumor suppressor genes assessed using a variety of laboratory methods. Associations of CIMP with outcome parameters were estimated using pooled odds ratio or standardized mean differences using random-effects model. RESULTS: We confirmed prior associations including female sex, older age, right-sided tumor location, poor differentiation, and microsatellite instability. In addition to the recognized association with BRAF mutations, CIMP was also associated with PIK3CA mutations and lack of mutations in KRAS and TP53. Evidence of an activated immune response was seen with high rates of tumor-infiltrating lymphocytes (but not peritumoral lymphocytes), Crohn-like infiltrates, and infiltration with Fusobacterium nucleatum bacteria. Additionally, CIMP tumors were associated with advance T-stage and presence of perineural and lymphovascular invasion. CONCLUSION: The meta-analysis highlights key features distinguishing CIMP in colorectal cancer, including molecular characteristics of an active immune response. Improved understanding of this unique molecular subtype of colorectal cancer may provide insights into prevention and treatment.

Abstract Background We examined the association between the maternal genotype for celiac disease‐associated variants and risk of neural tube defects (NTDs). Methods We conducted a case–control study, using data from the National Birth Defects Prevention Study. We evaluated 667 cases (women with an offspring with NTD) and 743 controls (women with an offspring without a birth defect). We classified women as having low, intermediate, or high risk of celiac disease based on human leukocyte antigen (HLA) variants. We used logistic regression to assess the relationship between HLA celiac risk group (low, intermediate, high) and risk of NTDs. Fifteen non‐HLA variants (identified from genome‐wide association studies of celiac disease) were individually evaluated and modeled additively. Results There was no association between HLA celiac risk group and NTDs (intermediate vs. low risk: aOR, 1.0; 95% CI, 0.8–1.3; high vs. low risk: aOR, 0.8; 95% CI, 0.5–1.3). Of the fifteen non‐HLA variants, we observed five significant associations after accounting for multiple comparisons. Three negative associations were observed with rs10903122, rs13314993, rs13151961 (aOR range: 0.69–0.81), and two positive associations were observed with rs13003464 and rs11221332 (aOR range: 1.27–1.73). Conclusion If confirmed, our results suggest that the maternal variants related to celiac disease may be involved in the risk of NTDs.

Introduction Hospitals are the primary worksite of over 5 million adults in the United States, and millions of meals are procured and consumed in this setting. Because many worksite nutrition initiatives use an ecological framework to improve the dietary habits of employees, the nutrition values of foods served in hospitals is receiving attention. Methods This study used the Hospital Nutrition Environment Scan for Cafeterias, Vending Machines, and Gift Shops to quantitatively describe the consumer nutrition environments of 39 hospitals in Southern California. Data were collected by visiting each facility once from February 2012 through May 2012. Results On average, hospitals achieved only 29%, 33%, and less than 1% of the total possible points for their cafeteria, vending machines, and gift shops sections, respectively; overall, hospitals scored 25% of the total possible points. Large facility size and contracted food service operations were associated with some healthy practices in hospital cafeterias, but we found no association between these variables and the sectional or overall nutrition composite scores. Conclusion The average consumer nutrition environment of hospitals in this sample was minimally conducive to healthful eating. Nutrition-related interventions are warranted in hospital settings.

It is commonly reported that rare variants may be more functionally related to complex diseases than common variants. However, individual rare variant association tests remain challenging due to low minor allele frequency in the available samples. This paper proposes an expectation maximization variable selection (EMVS) method to simultaneously detect common and rare variants at the individual variant level using family trio data. TRIO_RVEMVS was assessed in both large (1500 families) and small (350 families) datasets based on simulation. The performance of TRIO_RVEMVS was compared with gene-level kernel and burden association tests that use pedigree data (PedGene) and rare-variant extensions of the transmission disequilibrium test (RV-TDT). At the region level, TRIO_RVEMVS outperformed PedGene and RV-TDT when common variants were included. TRIO_RVEMVS performed competitively with PedGene and outperformed RV-TDT when the analysis was only restricted to rare variants. At the individual variants level, with 1,500 trios, the average true positive rate of individual rare variants that were polymorphic across 500 datasets was 12.20%, and the average false positive rate was 0.74%. In the datasets with 350 trios, the average true and false positive rates of individual rare variants were 13.10% and 1.30%, respectively. When applying TRIO_RVEMVS to real data from the Gabriella Miller Kids First Pediatric Research Program, it identified 3 rare variants in q24.21 and q24.22 associated with the risk of orofacial clefts in the Kids First European population.