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Background: Examining lung cancer (LC) cases in Virginia (VA) is essential due to its significant public health implications. By studying demographic, environmental, and socioeconomic variables, this paper aims to provide insights into the underlying drivers of LC prevalence in the state adjusted for spatial associations at the zipcode level. Methods: We model the available VA zipcode-level LC counts via (spatial) Poisson and negative binomial regression models, taking into account missing covariate data, zipcode-level spatial association and allow for overdispersion. Under latent Gaussian Markov Random Field (GMRF) assumptions, our Bayesian hierarchical model powered by Integrated Nested Laplace Approximation (INLA) considers simultaneous (spatial) imputation of all missing covariates through elegant prediction. The spatial random effect across zip codes follows a Conditional Autoregressive (CAR) prior. Results: Zip codes with elevated smoking indices demonstrated a corresponding increase in LC counts, underscoring the well-established connection between smoking and LC. Additionally, we observed a notable correlation between higher Social Deprivation Index (SDI) scores and increased LC counts, aligning with the prevalent pattern of heightened LC prevalence in regions characterized by lower income and education levels. On the demographic level, our findings indicated higher LC counts in zip codes with larger White and Black populations (with Whites having higher prevalence than Blacks), lower counts in zip codes with higher Hispanic populations (compared to non-Hispanics), and higher prevalence among women compared to men. Furthermore, zip codes with a larger population of elderly people (age ≥ 65 years) exhibited higher LC prevalence, consistent with established national patterns. Conclusions: This comprehensive analysis contributes to our understanding of the complex interplay of demographic and socioeconomic factors influencing LC disparities in VA at the zip code level, providing valuable information for targeted public health interventions and resource allocation. Implementation code is available at GitHub.

Abstract Tumor budding (TB) is a small tumor cell cluster with highly aggressive behavior located ahead of the invasive tumor front. However, the molecular and biological characteristics of TB and the regulatory mechanisms governing TB phenotypes remain unclear. This study reveals that TB exhibits a particular dynamic gene signature with stemness and partial epithelial‐mesenchymal transition (p‐EMT). Importantly, nuclear expression of CYTOR is identified to be the key regulator governing stemness and the p‐EMT phenotype of TB cells, and targeting CYTOR significantly inhibits TB formation, tumor growth and lymph node metastasis in head and neck squamous cell carcinoma (HNSCC). Mechanistically, CYTOR promotes tumorigenicity and metastasis of TB cells by facilitating the formation of FOSL1 phase‐separated condensates to establish FOSL1‐dependent super enhancers (SEs). Depletion of CYTOR leads to the disruption of FOSL1‐dependent SEs, which results in the inactivation of cancer stemness and pro‐metastatic genes. In turn, activation of FOSL1 promotes the transcription of CYTOR. These findings indicate that CYTOR is a super‐lncRNA that controls the stemness and metastasis of TB cells through facilitating the formation of FOSL1 phase separation and SEs, which may be an attractive target for therapeutic interventions in HNSCC.

Abstract We report co-electrolysis of seawater and carbon dioxide (CO2) gas in a solar cell-integrated membraneless microfluidic reactor for continuous synthesis of organic products. The microfluidic reactor was fabricated using polydimethylsiloxane substrate comprising of a central microchannel with a pair of inlets for injection of CO2 gas and seawater and an outlet for removal of organic products. A pair of copper electrodes were inserted into microchannel to ensure its direct interaction with incoming CO2 gas and seawater as they pass into the microchannel. The coupling of solar cell panels with electrodes generated a high-intensity electrical field across the electrodes at low voltage, which facilitated the co-electrolysis of CO2 and seawater. The paired electrolysis of CO2 gas and seawater produced a range of industrially important organics under influence of solar cell-mediated external electric field. The, as synthesized, organic compounds were collected downstream and identified using characterization techniques. Furthermore, the probable underlying electrochemical reaction mechanisms near the electrodes were proposed for synthesis of organic products. The inclusion of greenhouse CO2 gas as reactant, seawater as electrolyte, and solar energy as an inexpensive electric source for co-electrolysis initiation makes the microreactor a low-cost and sustainable alternative for CO2 sequestration and synthesis of organic compounds.

Abstract Background We examined whether there are racial disparities in pain management, opioid medicine prescriptions, symptom severity, and quality of life constructs in breast cancer survivors. Methods We conducted a secondary analysis of longitudinal data from the Women's Hormonal Therapy Initiation and Persistence (WHIP) study (n = 595), a longitudinal study of hormonal receptor‐positive breast cancer survivors. Upon study enrollment, patients completed a survey assessing an array of psychological, behavioral, and treatment outcomes, including adjuvant endocrine therapy (AET)‐induced symptoms, and provided a saliva biospecimen. Opioid prescription records were extracted from the health maintenance organizations (HMOs) pharmacy database. The final analytic sample included women with complete HMO pharmacy records for 1 year. Results There were 251 eligible patients, of which 169 (67.3%) were White. The average age was 61.09 years old (SD = 11.07). One hundred seventy‐two patients (68.5%) had received at least one opioid medication and 37.1% were prescribed opioids longer than 90 days (n = 93). Sixty‐four Black patients (78%) had a record of being prescribed with opioids compared to 64% of White patients (n = 108, p = 0.03). Black patients reported worse vasomotor, neuropsychological, and gastrointestinal symptoms, as well as lower quality of life and greater healthcare discrimination than White patients (p's

Background: Advances in sequencing technologies have allowed collection of massive genome-wide information that substantially advances lung cancer diagnosis and prognosis. Identifying influential markers for clinical endpoints of interest has been an indispensable and critical component of the statistical analysis pipeline. However, classical variable selection methods are not feasible or reliable for high-throughput genetic data. Our objective is to propose a model-free gene screening procedure for high-throughput right-censored data, and to develop a predictive gene signature for lung squamous cell carcinoma (LUSC) with the proposed procedure. Methods: A gene screening procedure was developed based on a recently proposed independence measure. The Cancer Genome Atlas (TCGA) data on LUSC was then studied. The screening procedure was conducted to narrow down the set of influential genes to 378 candidates. A penalized Cox model was then fitted to the reduced set, which further identified a 6-gene signature for LUSC prognosis. The 6-gene signature was validated on datasets from the Gene Expression Omnibus. Results: Both model-fitting and validation results reveal that our method selected influential genes that lead to biologically sensible findings as well as better predictive performance, compared to existing alternatives. According to our multivariable Cox regression analysis, the 6-gene signature was indeed a significant prognostic factor (p-value < 0.001) while controlling for clinical covariates. Conclusions: Gene screening as a fast dimension reduction technique plays an important role in analyzing high-throughput data. The main contribution of this paper is to introduce a fundamental yet pragmatic model-free gene screening approach that aids statistical analysis of right-censored cancer data, and provide a lateral comparison with other available methods in the context of LUSC.

Objective:Breast cancer is the most commonly diagnosed malignancy in US women. Risk assessment tools such as the Gail and Tyrer-Cuzick (TC) models calculate risk for breast cancer based on modifiable and non-modifiable factors in order to guide screening and prevention for high-risk patients. Screening with magnetic resonance imaging (MRI) in addition to mammography is recommended in high-risk patients (>20% lifetime risk on TC or other familial based models). Currently, no published data indicate these recommendations improve cancer detection.Materials and Methods:With the aim to determine what percentage lifetime risk (LR%) is associated with a statistically significant increase in cancer detection, the Virginia Commonwealth University (VCU) breast imaging database was reviewed to identify patients who received screening MRI.Results:The receiver operating characteristics (ROC) curves for the Gail and TC models and the rate of cancer detection correlated to 20% LR% were calculated. The Gail model was considered the control model as it is NOT considered a validated screening tool for MRI. TC is not more accurate than Gail when predicting benefit of breast MRI screening. (area under the curve (AUC): 0.6841, 0.6543 respectively, p = 0.828). Univariate analysis failed to demonstrate a statistically significant relationship between the Gail or TC LR % and diagnosis of breast cancer when using 20% as the cutoff for high-risk classification (p = 1.0, 0.369 respectively). Neither the TC nor the Gail risk calculators demonstrated a significant correlation between risk and the likelihood of diagnosis of breast cancer when screened with MRI.Conclusion:Larger cohort studies are necessary to determine the risk percentage most predictive of a breast cancer diagnosis using MRI as screening.

Objective: Men with non-alcoholic fatty liver disease (NAFLD) are more likely to progress to non-alcoholic steatohepatitis (NASH) and liver fibrosis than women. However, the underlying molecular mechanisms of this dimorphism is unclear. We have previously shown that mice with global deletion of SphK1, the enzyme that produces the bioactive sphingolipid metabolite sphingosine 1-phosphate (S1P), were protected from development of NASH. The aim of this study was to elucidate the role of hepatocyte-specific SphK1 in development of NASH and to compare its contribution to hepatosteatosis in male and female mice. Methods: We assessed mouse livers in early-stage fibrosis induced by high fat feeding, using single harmonic generation microscopy, LC-MS/MS analysis of hydroxyproline levels, and expression of fibrosis markers. We identified an antifibrotic intercellular signaling mechanism by culturing primary mouse hepatocytes alongside, and in co-culture with, LX2 hepatic stellate cells. Results: We generated hepatocyte-specific SphK1 knockout mice (SphK1-hKO). Unlike the global knockout, SphK1-hKO male mice were not protected from diet-induced steatosis, inflammation, or fibrogenesis. In contrast, female SphK1-hKO mice were protected from inflammation. Surprisingly, however, in these female mice, there was a ∼10-fold increase in the fibrosis markers Col1α1 and 2–3 fold induction of alpha smooth muscle actin and the pro-fibrotic chemokine CCL5. Because increased fibrosis in female SphK1-hKO mice occurred despite an attenuated inflammatory response, we investigated the crosstalk between hepatocytes and hepatic stellate cells, central players in fibrosis. We found that estrogen stimulated release of S1P from female hepatocytes preventing TGFβ-induced expression of Col1α1 in HSCs via S1PR3. Conclusions: The results revealed a novel pathway of estrogen-mediated cross-talk between hepatocytes and HSCs that may contribute to sex differences in NAFLD through an anti-fibrogenic function of the S1P/S1PR3 axis. This pathway is susceptible to pharmacologic manipulation, which may lead to novel therapeutic strategies.

Purpose: The aim of this study was to examine the pathology of retinoblastoma (RB) seeds with supportive evidence by field emission scanning electron microscopy and Raman spectroscopy. Methods: This study was a laboratory-based observational study. Enucleated eyeballs received in the ocular pathology department of a tertiary eye care center in northeast India were included in the cohort after obtaining written informed consent during the surgery. The study was carried out for 6 years (2015–2020). Most of the eyeballs were Group-E RBs. Standard eyeballs sectioning were done by bread loaf techniques. Gross documentations included RB seeds seen in the smallest calotte done with utmost care. Seeds were documented also in permanent sections. Scanning electron microscopy and Raman spectroscopy were carried out in an index case. Results: Out of the total 59 cases, 35 RB cases had different seedings. The mean age at enucleation was 2.9 years. RB seeds were seen in vitreous (n = 19), subretinal plus vitreous (n = 7), anterior chamber (n = 1), over crystalline lens (n = 3), retinal surface (n = 1), retinal pigment epithelium (RPE; n = 2), subretinal (n = 1), calcified seeds (n = 2). Other characteristics were dusts (n = 7), clouds (n = 11), spheres (n = 4), and unspecified type (n = 13). Histopathological high-risk factors showed significant choroidal (n = 22) and optic nerve (n = 15) involvement. Few cases had extraocular spread. Undifferentiated tumor (n = 24) was seen with higher evidence of necrosis (n = 23). Raman spectra differentiated the seeds from the normal tissue on the basis of lipid and protein content. Conclusion: This study highlights the different types of RB seeds with high-risk factors. The morphology of those seeds showed the difference between vitreous and subretinal seeds under advanced microscopic observations.

BackgroundAdvanced cancer states perpetuate health-related disparities. Peritoneal-based cancers are clinically advanced cancers that present a significant clinical dilemma. Peritoneal cancers are managed aggressively with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). While racial and ethnic disparities are prevalent in cancer, there are no studies investigating if racial disparities exist in patients with peritoneal carcinomatosis managed with CRS and HIPEC. We hypothesized that this advanced disease state further delineates racial disparities.MethodsA retrospective chart review was conducted on patients with peritoneal carcinomatosis receiving CRS and HIPEC at a single institution from January 1, 2017-October 4, 2021. Descriptive statistics were used to compare racial groups. The Cox Proportional Hazards Model and Log Rank Test were used for multivariate and overall survival analysis.ResultsIn total, 67 patients underwent CRS and HIPEC, of which 41 (61.2%) were White, 20 (29.8%) were Black, 3 (4.5%) were Asian, and 3 (4.5%) were Other race. When compared to White patients, Black patients had lower income (p=0.0011), higher incidence of hypertension (p=0.0231), and lower performance status (p=0.0441). Cancer type, including colorectal, appendiceal, ovarian, etc., was similar between groups (p=0.8703). Despite these differences in sociodemographic and morbidity factors, when comparing Black patients to White patients, there were no differences in peritoneal cancer index score (13.2 vs. 12.3, p=0.6932), estimated blood loss (748 vs. 655 mL, p=0.6332), minor/major complication rates (1.1 vs. 1.2, p=0.7281; 0.4 vs. 0.7, p=0.3470, respectively), 30-day readmission rates (25.0% vs. 17.1%, p=0.6210), disease recurrence (40.0% vs. 51.2%, p=0.3667), or 30-day mortality (0.0% vs. 2.4%, p=1.0000). Overall survival was similar for Black and White patients (p=0.2693). The occurrence of a major complication was the only factor associated with overall survival (HR 2.188 [1.502, 3.188], p< 0.0001).ConclusionsDespite differences in patient socioeconomic factors and comorbid conditions, outcomes were similar between Black and White patients receiving CRS and HIPEC at our institution. While larger studies with more diverse patient populations are needed to confirm these findings, our data provide evidence that aggressive surgical management across diverse patient populations allows for equitable outcomes.

Pre-existing maternal overweight/obesity and pregnancy weight gain are associated with adverse birth outcomes such as low birth weight and prematurity, which may increase the risk of developmental tooth defects and early childhood caries. We sought to investigate the association between prepregnancy BMI, gestational weight gain (GWG) and the risk of early childhood caries. Data from 1,429 mother-offspring participants of the 1991/1992 Avon Longitudinal Study of Parents and Children were analyzed. The exposures were prepregnancy BMI (under/normal weight vs. overweight/obese), and gestational weight gain (GWG) based on the Institute of Medicine's recommended levels. The main outcome measured was offspring caries experience determined by clinical oral examinations at three time points. Log binomial regression estimated risk ratios and 95% confidence intervals. Seventy six percent (76%) of the mothers were under/normal weight prepregnancy, 39% and 26% respectively gained less and more than the recommended weight for their prepregnancy BMI during pregnancy. Being overweight/obese prepregnancy was associated with unadjusted RR (95% CI) of offspring caries of 1.16 (0.90, 1.51) at 31-months, 1.20 (0.96, 1.49) at 43-months and 1.09 (0.91, 1.30) at 61-months. GWG less than recommended was associated with higher unadjusted offspring caries experience of 1.13 (0.86, 1.48), 1.17 (0.92, 1.48) and 1.04 (0.87, 1.25) at 31-months, 43-months and 61-months respectively. There was insufficient evidence to indicate an association between prepregnancy BMI and gestational weight gain on offspring caries experience risk.

Microbiome data are becoming increasingly available in large health cohorts, yet metabolomics data are still scant. While many studies generate microbiome data, they lack matched metabolomics data or have considerable missing proportions of metabolites. Since metabolomics is key to understanding microbial and general biological activities, the possibility of imputing individual metabolites or inferring metabolomics pathways from microbial taxonomy or metagenomics is intriguing. Importantly, current metabolomics profiling methods such as the HMP Unified Metabolic Analysis Network (HUMAnN) have unknown accuracy and are limited in their ability to predict individual metabolites. To address this gap, we developed a novel metabolite prediction method, and we present its application and evaluation in an oral microbiome study. The new method for predicting metabolites using microbiome data (ENVIM) is based on the elastic net model (ENM). ENVIM introduces an extra step to ENM to consider variable importance (VI) scores, and thus, achieves better prediction power. We investigate the metabolite prediction performance of ENVIM using metagenomic and metatranscriptomic data in a supragingival biofilm multi-omics dataset of 289 children ages 3–5 who were participants of a community-based study of early childhood oral health (ZOE 2.0) in North Carolina, United States. We further validate ENVIM in two additional publicly available multi-omics datasets generated from studies of gut health. We select gene family sets based on variable importance scores and modify the existing ENM strategy used in the MelonnPan prediction software to accommodate the unique features of microbiome and metabolome data. We evaluate metagenomic and metatranscriptomic predictors and compare the prediction performance of ENVIM to the standard ENM employed in MelonnPan. The newly developed ENVIM method showed superior metabolite predictive accuracy than MelonnPan when trained with metatranscriptomics data only, metagenomics data only, or both. Better metabolite prediction is achieved in the gut microbiome compared with the oral microbiome setting. We report the best-predictable compounds in all these three datasets from two different body sites. For example, the metabolites trehalose, maltose, stachyose, and ribose are all well predicted by the supragingival microbiome.

Objectives: Lymph node (LN) metastasis and genomic profiles are important prognostic factors in endometrial cancer (EMCA). However, the prognostic significance of low volume metastasis found in sentinel lymph nodes (SLN) is unknown. We sought to determine if genomic mutations were associated with metastatic volume. Methods: Surgically staged women with EC who were enrolled in both a SLN clinical trial and tumor sequencing protocol were eligible. Relevant targets were enriched by a custom designed Agilent SureSelect hybrid capture enrichment library using standard protocols. Three specific gene mutations were evaluated, TP53, PTEN and PIK3CA in the primary tumor of patients with LN negative, LN positive and ITC disease. Results: 42 patients were eligible; of these, 7 (16.7%) had ITC only and 7 (16.7%) had micrometastatic or macrometastatic (LN positive) disease. No differences were seen in TP53, PIK3CA or PTEN between groups. All ITC patients with TP53 mutations were of non-endometrioid histology (2/7). Deeper myometrial invasion and lymph vascular space invasion were more likely to occur in the LN positive group (p

Background: Parental reports of their children’s health status is integral to pediatric medical and dental care. Therefore, understanding the accuracy of such reports is vital. Our objectives were to (1) assess the correlation between maternal reports of their children’s indicators of caries experience (subjective assessment) and actual caries status determined by oral examination (objective assessment), and (2) identify potential modifiers of this correlation. Methods: Longitudinal data from the Avon longitudinal study of parents and children (n = 1429) was used to assess the correlation between maternal reports of the number of missing and filled teeth of children aged 38 months, 54 months, and 5.5 years and clinical oral examinations of decayed, missing and filled teeth conducted when the same children were 31, 43 months, and five years of age. Homogeneity chi-square tests assessed differences in correlations according to sociodemographic factors. Results: Overall, we found a statistically significant correlation that was weak to moderate in magnitude. Maternal reports of missing teeth at 38 months was significantly correlated with decayed teeth, 0.27 (p < 0.001); missing teeth, 0.23 (p < 0.001), and the decayed, missing and filled (dmft) index, 0.35 (p < 0.001) based on oral examination at 31 months. A maternal report of filled teeth at 54 months was significantly correlated with decayed teeth, 0.30 (p < 0.001); filled teeth 0.30 (p < 0.001), and dmft 0.40 (p < 0.001) at 43 months. Mothers tended to underestimate the extent of missing and filled teeth in their children irrespective of the child’s age, but the extent of underestimation was greater among younger children. Maternal age, education level, and whether the child had ever visited a dentist were significant modifiers of subjective and objective caries assessments. Conclusions: From a clinical and dental public health perspective, our findings of a weak to moderate correlation of maternal assessments of their children’s caries experience may be concerning when reporting the burden of dental diseases in large population studies or for surveillance purposes that rely on self-reported measures and must therefore be utilized with caution because of the potential to result in underestimated disease burden.

Three-dimensional long-wave nonlinear analysis of the instabilities engendered by van der Waals forces in a thin (<100 nm) viscous bilayer resting on a rigid substrate is presented. The bilayers are classified based on the macroscopic dewetting behavior of the films, and the three-dimensional morphological evolutions of the films are studied in each case. The dewetting of the bilayers is initiated by one of the two basic modes at the interfaces: in-phase “bending” and out-of-phase “squeezing”. We show that the thicknesses, surface energies, and viscosities of the films have significant influence on the mode selection, pathway, of dewetting, and the final morphology of dewetting. Different equilibrium morphologies are obtained by tuning the nature and the strength of the intermolecular forces present at the films, which include: (i) an array of channels and ridges in the lower layer with the upper liquid embedded inside the channels, (ii) islands in the lower layer with the upper layer embedded in the interstitial spaces, and (iii) the lower layer droplets encapsulated by the upper layer. [ABSTRACT FROM AUTHOR]

A back-gate-field-effect-transistor (BG-FET) has been developed to selectively detect ammonia and urea. The BG-FET was prepared on a p-type Si substrate with an n-type channel of CdS-TiO2 nanocomposite and poly-methyl methacrylate film as dielectric layer. The reusability of the sensor was ensured by putting it as a cover to a chamber where samples were detected. The BG-FET showed an increase in drain current with the increase in ammonia release from chamber because higher numbers of charge carriers were created when ammonia adsorped on CdS-TiO2 nanostructures. Control experiments suggested that the variation in current-to-voltage response of BG-FET could also be calibrated to measure the activity of a host of other hazardous gases. The lowest concentration of ammonia detected was ∼0.85 ppm with a response time of 30 s at a gate voltage of 0.5 V or less, which were superior than available field effect transistors ammonia sensors. Addition of urease in urine liberated ammonia equivalent to urea content in urine, which could be detected by the proposed BGFET. The urea-urease enzyme catalysis reaction made the sensor specific in detecting the biomarker. The accuracy, sensitivity, and reusability of the device was found to be suitable to develop a point-of-care testing device for ammonia and urea detection. [ABSTRACT FROM AUTHOR]