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Abstract Objective This study used real-world observational data to compare profiles of patients receiving different first-line treatment for hormone receptor positive (ER+), HER2 negative, metastatic breast cancer (MBC): CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) versus ET alone. Method From a nationwide electronic health record-derived Flatiron Health de-identified database including 280 US cancer clinics, we identified patients with hormone receptor positive, HER2 negative, metastatic breast cancer receiving 1st -line therapy with ET alone or CDK4/6i plus ET between February 2015 and November 2021. Patient sociodemographic status, MBC treatment regimen and outcomes were the focus of this analysis. Patient characteristics were compared using t-tests and chi-square tests. Logistic regression analysis was performed to examine the association of patient characteristics with the likelihood of receiving 1st -line CDK4/6i plus ET vs. ET alone. Kaplan-Meier method and Cox proportional hazards were used to test the impact of 1st -line treatment regimen on real-world progression-free survival (PFS) and overall survival (OS). Baseline characteristics were balanced using inverse probability weighting (IPW). Results The study population included 3,917 patients receiving CDK4/6i plus ET (n = 2170) and ET alone (n = 1747) for their MBC. Compared to patients receiving ET alone, those receiving CDK4/6i plus ET were younger (mean age 66.8 vs. 68.6, p

Abstract Background High consumption of sugar-sweetened beverages (SSB) is a global health concern. Additionally, sugar-sweetened beverage (SSB) consumption is disproportionately high among adolescents and adults in rural Appalachia. The primary study objective is to determine the intervention effects of Kids SIPsmartER on students’ SSB consumption. Secondary objectives focus on caregivers’ SSB consumption and secondary student and caregiver outcomes [e.g, body mass index (BMI), quality of life (QOL)]. Methods This Type 1 hybrid, cluster randomized controlled trial includes 12 Appalachian middle schools (6 randomized to Kids SIPsmartER and 6 to control). Kids SIPsmartER is a 6-month, 12 lesson, multi-level, school-based, behavior and health literacy program aimed at reducing SSB among 7th grade middle school students. The program also incorporates a two-way text message strategy for caregivers. In this primary prevention intervention, all 7th grade students and their caregivers from participating schools were eligible to participate, regardless of baseline SSB consumption. Validated instruments were used to assess SSB behaviors and QOL. Height and weight were objectively measured in students and self-reported by caregivers. Analyses included modified two-part models with time fixed effects that controlled for relevant demographics and included school cluster robust standard errors. Results Of the 526 students and 220 caregivers, mean (SD) ages were 12.7 (0.5) and 40.6 (6.7) years, respectively. Students were 55% female. Caregivers were mostly female (95%) and White (93%); 25% had a high school education or less and 33% had an annual household income less than $50,000. Regardless of SSB intake at baseline and relative to control participants, SSB significantly decreased among students [-7.2 ounces/day (95% CI = -10.7, -3.7); p 24 SSB ounces/day at baseline (i.e., high consumers), the ES increased to 0.45 and 0.95, respectively. There were no significant effects for student or caregiver QOL indicators or objectively measured student BMI; however, caregiver self-reported BMI significantly decreased in the intervention versus control schools (p = 0.001). Conclusions Kids SIPsmartER was effective at reducing SSB consumption among students and their caregivers in the rural, medically underserved Appalachian region. Importantly, SSB effects were even stronger among students and caregivers who were high consumers at baseline. Trial registration Clincialtrials.gov: NCT03740113. Registered 14 November 2018– Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03740113 .

Abstract Background Adult smoking rates in the USA are highest in economically depressed rural Appalachia. Pharmacist-delivered tobacco cessation support that incorporates medication therapy management (such as the QuitAid intervention) is a promising approach to address this need. Methods Twenty-four adult smokers recruited between September and November 2021 through an independent pharmacy in rural Appalachia were randomized in a non-blinded 2 × 2 × 2 factorial design to (1) pharmacist delivered QuitAid intervention (yes vs. no); (2) combination nicotine replacement therapy (NRT) gum + NRT patch (vs. NRT patch); and/or (3) 8 weeks of NRT (vs. standard 4 weeks). Participants received 4 weeks of NRT patch in addition to the components to which they were assigned. Participants completed baseline and 3-month follow-up assessments. Primary outcomes were feasibility of recruitment and randomization, retention, treatment adherence, and fidelity. Results Participants were recruited in 7 weeks primarily through a referral process, commonly referred to as ask-advise-connect (61%). Participants were on average 52.4 years old, 29.2% were male and the majority were white (91.6%) and Non-Hispanic (91.7%). There was a high level of adherence to the interventions, with 85% of QuitAid sessions completed, 83.3% of the patch used, and 54.5% of gum used. Participants reported a high level of satisfaction with the program, and there was a high level of retention (92%). Conclusions This demonstration pilot randomized controlled study indicates that an ask-advise-connect model for connecting rural smokers to smoking cessation support and providing QuitAid for smoking cessation is feasible and acceptable among rural Appalachian smokers and independent pharmacists. Further investigation into the efficacy of a pharmacist-delivered approach for smoking cessation is needed. Trial registration The trial was retrospectively registered at ClinicalTrials.gov. Trial #: NCT05649241.

Abstract Background Cronkhite-Canada syndrome (CCS) is a rare, nonhereditary disease characterized by diffuse gastrointestinal polyposis and ectodermal abnormalities. Although it has been proposed to be a chronic inflammatory condition, direct evidence of its pathogenesis is lacking. This study aims to investigate the pathophysiology of CCS by analyzing transcriptomic changes in the colonic microenvironment. Methods Next-generation sequencing-based genome-wide transcriptional profiling was performed on colonic hamartomatous polyps from four CCS patients and normal colonic mucosa from four healthy volunteers. Analyses of differential expression and multiple enrichment analyses were conducted from the molecular level to the cellular level. Quantitative real-time PCR (qRT-PCR) was carried out to validate the sequencing accuracy in samples from six CCS patients and six healthy volunteers. Results A total of 543 differentially expressed genes were identified, including an abundance of CC- and CXC-chemokines. Innate immune response-related pathways and processes, such as leukocyte chemotaxis, cytokine production, IL-17, TNF, IL-1 and NF-kB signaling pathways, were prominently enhanced in CCS colonic polyps. Upregulation of wound healing, epithelial-mesenchymal transition, Wnt, and PI3K-Akt signaling pathways were also observed. Enrichment analyses at different levels identified extracellular structure disorganization, dysfunction of the gut mucosal barrier, and increased angiogenesis. Validation by qRT-PCR confirmed increased expression of the LCN2, IL1B, CXCL1, and CXCL3 genes in CCS colonic polyps. Conclusions This case-control whole transcriptome analysis of active CCS colonic hamartomatous polyps revealed intricate molecular pathways, emphasizing the role of the innate immune response, extracellular matrix disorganization, inflammatory cell infiltration, increased angiogenesis, and potential epithelial to mesenchymal transition. These findings supports CCS as a chronic inflammatory condition and sheds light on potential therapeutic targets, paving the way for more effective and personalized management of CCS in the future.

Abstract Background Existing financial hardship screening does not capture the multifaceted and dynamic nature of the problem. The use of existing health system data is a promising way to enable scalable and sustainable financial hardship screening. Methods We used existing data from 303 adult patients with cancer at the University of Virginia Comprehensive Cancer Center (2016–2018). All received distress screening and had a valid financial assistance screening based solely on household size‐adjusted income. We constructed a composite index that integrates multiple existing health system data (Epic, distress screening, and cancer registry) to assess comprehensive financial hardship (e.g., material conditions, psychological responses, and coping behaviors). We examined differences of at‐risk patients identified by our composite index and by existing single‐dimension criterion. Dynamics of financial hardship over time, by age, and cancer type, were examined by fractional probit models. Results At‐risk patients identified by the composite index were generally younger, better educated, and had a higher annual household income, though they had lower health insurance coverage. Identified periods to intervene for most patients are before formal diagnosis, 2 years, and 6 years after diagnosis. Within 2 years of diagnosis and more than 4 years after diagnosis appear critical for subgroups of patients who may suffer from financial hardship disparities. Conclusion Existing health system data provides opportunities to systematically measure and track financial hardship in a systematic, scalable and sustainable way. We find that the dimensions of financial hardship can exhibit different patterns over time and across patient subgroups, which can guide targeted interventions. The scalability of the algorithm is limited by existing data availability.

Abstract Background Fruit and vegetable (FV) consumption in children in the United States (US) is very low. Adequate FV consumption is required for proper development during childhood, and dietary habits are established during preschool-age and tend to persist into adulthood. As most U.S. preschool-aged children attend childcare or preschool, this may be an opportune time and setting to conduct interventions to improve FV intake. These interventions should be based in theory and use behavior change techniques (BCTs) to explain mechanisms for expected change. To date, no published reviews have examined the effectiveness of childcare- or preschool-based FV interventions in preschoolers and their use of theoretical frameworks and BCTs. Methods This systematic review was completed adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were randomized controlled trials (RCTs) published between 2012 and 2022 of interventions to improve diet or FV intake in preschoolers (aged 2–5 years) in childcare or preschool-settings. A search of four databases was conducted between in September 2022 using search terms pertaining to the study’s primary aim (FV consumption), age group (preschool-aged), settings (US childcare or preschool settings), and study design (RCT). Additional criteria were objective measures of FV consumption or skin carotenoids, as a proxy for FV intake. Included studies were narratively synthesized based on intervention type, measured effect, and use of theory and BCTs. Results The search resulted in six studies that reported on nine interventions. Overall, six interventions increased FV intake, of which five used nutrition education and one manipulated the feeding environment. Among the three interventions with no measured effect, two manipulated the feeding environment and one used peer modeling. Effective studies used at least three BCTs, though no pattern was observed between use of theory or BCTs and intervention effect. Conclusions While several studies have shown promising results, the limited number of studies identified in this review highlights key gaps in this field: there is a need for studies to test FV interventions in US childcare settings that use objective measures of FV intake, directly compare intervention components and BCTs, are theory-based, and assess long-term behavior change.

ObjectivesWe conducted a comprehensive meta-analysis to compare the effectiveness and safety of fluoroscopy-guided air enema reduction (FGAR) and ultrasound-guided hydrostatic enema reduction (UGHR) for the treatment of intussusception in pediatric patients.MethodsA systematic review and meta-analysis were conducted on retrospective studies obtained from various databases, including PUBMED, MEDLINE, Cochrane, Google Scholar, China National Knowledge Infrastructure (CNKI), WanFang, and VIP Database. The search included publications from January 1, 2003, to March 31, 2023, with the last search done on Jan 15, 2023.ResultsWe included 49 randomized controlled studies and retrospective cohort studies involving a total of 9,391 patients, with 4,841 in the UGHR and 4,550 in the FGAR. Specifically, UGHR exhibited a significantly shorter time to reduction (WMD = -4.183, 95% CI = (-5.402, -2.964), P < 0.001), a higher rate of successful reduction (RR = 1.128, 95% CI = (1.099, 1.157), P < 0.001), and a reduced length of hospital stay (WMD = -1.215, 95% CI = (-1.58, -0.85), P < 0.001). Furthermore, UGHR repositioning was associated with a diminished overall complication rate (RR = 0.296, 95% CI = (0.225, 0.389), P < 0.001) and a lowered incidence of perforation (RR = 0.405, 95% CI = (0.244, 0.670), P < 0.001).ConclusionUGHR offers the benefits of being non-radioactive, achieving a shorter reduction time, demonstrating a higher success rate in repositioning in particular, resulting in a reduced length of postoperative hospital stay, and yielding a lower overall incidence of postoperative complications, including a reduced risk of associated perforations.

Abstract. Background:. Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents. Methods:. We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study. Results:. Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44–0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43–0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43–0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13–1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo. Conclusions:. Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence. Registration:. PROSPERO, No. CRD42022296376

Background Behavioral weight loss programs often prescribe physical activity (PA) goals in terms of minutes/week of moderate-to-vigorous PA (MVPA) and steps/day. However, the impact of meeting each type of goal prescription on weight loss is unclear, particularly in digitally-based (eHealth/mHealth) programs. This secondary analysis of a randomized trial examined the effects of meeting steps-based and minutes-based goals on weight loss in an eHealth behavioral weight control program.Methods Adults in the control arm received a 6-month online behavioral weight loss intervention with prescribed weekly goals for daily steps and minutes of MVPA. The number of weeks steps-based and minutes-based goals were met (≥100% and ≥75% thresholds) based on self-reported PA were examined as predictors of 6-month weight loss among those providing weight outcomes (n = 172; 81% of control arm) using a systems regression approach.Results Participants (BMI 35.6 kg/m2; 90.1% female; 48.7 years of age) met weekly goals for MVPA (7.1 ± 6.4 weeks) more often than steps (3.5 ± 5.5 weeks, P

BackgroundThe psychosocial needs and risks of children with cancer and their families are well-documented including increased risk of parental distress, posttraumatic stress, and anxiety. There is a critical need to provide evidence-based psychosocial care to parents and caregivers of children with cancer. Digital health interventions are important to address many barriers to in-person intervention delivery but are not widely used in pediatric psychosocial cancer care. The COVID-19 pandemic has reinforced the need for flexible, acceptable, and accessible psychosocial digital health interventions. The Electronic Surviving Cancer Competently Intervention Program (eSCCIP) is an innovative digital health intervention for parents and caregivers of children with cancer, delivered through a combination of self-guided web-based content and supplemented by 3 telehealth follow-up sessions with a trained telehealth guide. A Spanish language adaptation of eSCCIP, El Programa Electronico de Intervencion para Superar Cancer Competentemente (eSCCIP-SP), has been developed. The self-guided web-based cores of eSCCIP/eSCCIP-SP are a mix of didactic video content, multifamily video discussion groups featuring parents of children with cancer, and hands-on web-based activities. ObjectiveThe objective of this study is to test eSCCIP/eSCCIP-SP in a multisite randomized controlled trial, compared to an internet-based education control condition consisting of information specifically focused on concerns relevant to parents and caregivers of children with cancer. MethodsUsing a randomized controlled clinical trial design, 350 eligible parents and caregivers of children with cancer will be randomly assigned to the intervention (eSCCIP/eSCCIP-SP) or an education control condition. Data will be collected at 3 time points: preintervention (prior to randomization), immediately post intervention (after 6 weeks), and at a 3-month follow-up (from baseline). Participants randomized to either condition will receive study material (eSCCIP/eSCCIP-SP intervention or education control website) in English or Spanish, based on the primary language spoken in the home and participant preference. ResultsThe primary study end point is a reduction in acute distress from baseline to postintervention, with secondary end points focused on reductions in symptoms of posttraumatic stress and anxiety, and improvements in coping self-efficacy and cognitive coping. An additional exploratory aim will be focused on implementation strategies and potential costs and cost-savings of eSCCIP/eSCCIP-SP, laying the groundwork for future trials focused on dissemination and implementation, stepped-care models, and intervention refinement. ConclusionsThis trial will provide necessary data to evaluate the efficacy of eSCCIP/eSCCIP-SP. This intervention has the potential to be an easily scalable and highly impactful psychosocial treatment option for parents and caregivers of children with cancer. Trial RegistrationClinicalTrials.gov NCT05294302; https://clinicaltrials.gov/ct2/show/NCT05294302 International Registered Report Identifier (IRRID)PRR1-10.2196/46339

OBJECTIVE: Few studies have reported the cost and cost-effectiveness of workplace interventions to reduce sedentary time. The purpose of this study was to complete an economic evaluation of a multilevel intervention to reduce sitting time and increase light-intensity physical activity (LPA) among employees. METHODS: We conducted a retrospective within-trial cost and cost-effectiveness analysis (CEA) to compare a 12-month multilevel intervention with (STAND+) and without (MOVE+) a sit-stand workstation, across 24 worksites (N=630 employee participants) enrolled in a cluster randomized clinical trial. We estimated the intervention costs using activity-based costing strategy. The intervention costs were further expressed as per person and per worksite. CEA was conducted using an incremental cost-effectiveness ratio (ICER) metric, expressed as costs for additional unit of sitting time (minute/day), LPA (minutes/day), cardiometabolic risk score, and quality-adjusted life years (QALY) increased/decreased at 12 months. We assessed the cost analysis and CEA from the organizational (ie, employer) perspective with a one-year time horizon. RESULTS: Total intervention costs were $134 and $72 per person, and $3939 and $1650 per worksite for the STAND+ (N worksites = 12; N employees = 354) and MOVE+ (N worksites = 12; N employees = 276) interventions, respectively. The ICER was $1 (95% CI $0.8–1.4) for each additional minute reduction of workplace sitting time (standardized to 8-hour workday); and $4656 per QALY gained at 12 months. There was a modest and non-significant change of loss of work productivity improvement (-0.03 hours, 95% CI -4.16–4.09 hours), which was associated with a $0.34 return for every $1 invested. CONCLUSIONS: The multi-level intervention with sit-stand workstations has the potential to be widely implemented to reduce workplace sitting time. Future research into work productivity outcomes in terms of cost-benefits for employers is warranted.

To enhance the rate of argon–oxygen refining of ferroalloys, this article is based on the physical and chemical reactions of the smelting process as well as the actual smelting data. A mechanistic model of the rate of change of oxygen supply and carbon content in the smelting process and the temperature of the reaction fluid in the furnace is established. An expert internal model control framework with furnace temperature and carbon content as output and oxygen supply rate as input is constructed. An adaptive parameter adjustment mechanism is added to the control framework by combining data on the maximum gas supply rate and temperature threshold of the stage in the actual production process. The method improves smelting speed and smelting accuracy compared to the general method. It is also able to adjust the furnace temperature according to the actual smelting situation. The actual smelting was carried out according to this method, the improved method reduced the smelting time by 12.79% compared to the general method, and the furnace temperature was controlled below 1950 K.

ObjectiveTo evaluate the effectiveness of two technology-enhanced interventions for diabetes prevention among adults at risk for developing diabetes in a primary care setting.MethodsThe DiaBEAT-it study employed a hybrid 2-group preference (Choice) and 3-group randomized controlled (RCT) design. This paper presents weight related primary outcomes of the RCT arm. Patients from Southwest Virginia were identified through the Carilion Clinic electronic health records. Eligible participants (18 and older, BMI ≥ 25, no Type 2 Diabetes) were randomized to either Choice (n = 264) or RCT (n = 334). RCT individuals were further randomized to one of three groups: (1) a 2-h small group class to help patients develop a personal action plan to prevent diabetes (SC, n = 117); (2) a 2-h small group class plus automated telephone calls using an interactive voice response system (IVR) to help participants initiate weight loss through a healthful diet and regular physical activity (Class/IVR, n = 110); or (3) a DVD with same content as the class plus the same IVR calls over a period of 12 months (DVD/IVR, n = 107).ResultsOf the 334 participants that were randomized, 232 (69%) had study measured weights at 6 months, 221 (66%) at 12 months, and 208 (62%) at 18 months. Class/IVR participants were less likely to complete weight measures than SC or DVD/IVR. Intention to treat analyses, controlling for gender, race, age and baseline BMI, showed that DVD/IVR and Class/IVR led to reductions in BMI at 6 (DVD/IVR −0.94, p < 0.001; Class/IVR −0.70, p < 0.01), 12 (DVD/IVR −0.88, p < 0.001; Class/IVR-0.82, p < 0.001) and 18 (DVD/IVR −0.78, p < 0.001; Class/IVR −0.58, p < 0.01) months. All three groups showed a significant number of participants losing at least 5% of their body weight at 12 months (DVD/IVR 26.87%; Class/IVR 21.62%; SC 16.85%). When comparing groups, DVD/IVR were significantly more likely to decrease BMI at 6 months (p < 0.05) and maintain the reduction at 18 months (p < 0.05) when compared to SC. There were no differences between the other groups.ConclusionsThe DiaBEAT-it interventions show promise in responding to the need for scalable, effective methods to manage obesity and prevent diabetes in primary care settings that do not over burden primary care clinics and providers.Registrationhttps://clinicaltrials.gov/ct2/show/NCT02162901, identifier: NCT02162901.

Abstract This research measures the epidemiological and economic impact of COVID-19 spread in the US under different mitigation scenarios, comprising of non-pharmaceutical interventions. A detailed disease model of COVID-19 is combined with a model of the US economy to estimate the direct impact of labor supply shock to each sector arising from morbidity, mortality, and lockdown, as well as the indirect impact caused by the interdependencies between sectors. During a lockdown, estimates of jobs that are workable from home in each sector are used to modify the shock to labor supply. Results show trade-offs between economic losses, and lives saved and infections averted are non-linear in compliance to social distancing and the duration of the lockdown. Sectors that are worst hit are not the labor-intensive sectors such as the Agriculture sector and the Construction sector, but the ones with high valued jobs such as the Professional Services, even after the teleworkability of jobs is accounted for. Additionally, the findings show that a low compliance to interventions can be overcome by a longer shutdown period and vice versa to arrive at similar epidemiological impact but their net effect on economic loss depends on the interplay between the marginal gains from averting infections and deaths, versus the marginal loss from having healthy workers stay at home during the shutdown.

Improved health-related quality of life (HRQoL) is one benefit of physical activity. Yet, there is limited intervention research exploring (1) whether changes in physical activity influence changes in HRQoL among community-based populations and (2) if baseline obesity status influences the relationships. This exploratory analysis used secondary data from rural Appalachian adults who completed the MoveMore arm of a larger randomized control trial (n = 105, Mage = 41.8, 82 % female, 96 % White, Mincome= $25,911). Specifically, this study examined associations among changes in physical activity and HRQOL and whether baseline obesity status moderated changes. Three HRQoL variables (self-rated health status, total unhealthy days, days poor health impacted activities) and two physical activity variables [weekly moderate-vigorous physical activity (MVPA) minutes, weekly strength training minutes] were collected at baseline and 6-months. Regression models, adjusted for age, gender, race, income, education, assessed associations between physical activity and HRQoL change variables. Moderation analyses explored the influence of baseline obesity status on these relationships. Participants reported significant improvements in self-rated health status (P = 0.001), weekly MVPA minutes (P = 0.008), and weekly strength training minutes (P

Abstract Background Abnormal activation of the coagulation system has been reported in patients with malignancies, but its prognostic significance in biliary tract cancer (BTC) remains unclear. This study aims to analyze and compare the prognostic value of coagulation indices in patients with BTC. Methods The medical records of 450 patients with BTC who underwent surgical resection at our hospital between 2003 and 2017 were retrospectively analyzed. Time-dependent receiver operating characteristic curves were plotted to compare the predictive accuracy of coagulation indices. A predictive nomogram for overall survival (OS) was established based on the Cox regression analysis and validated in both the training and validation cohorts. A novel stratification model was created according to the total points of the nomogram. Results Fibrinogen and international normalized ratio (INR) had the best predictive accuracy among the coagulation indices considered and were also the independent prognostic factors for OS. The nomogram and the novel stratification model had satisfactory performance and outperformed TNM staging. Conclusions The study demonstrated that coagulation indices are valuable in predicting OS in BTC, with fibrinogen and INR having the best predictive ability. The nomogram and the novel stratification model could be applied to predict survival for patients with BTC.

Abstract Background Modifying a household’s food environment by targeting a single retailer type, like supermarkets, has a limited impact on dietary outcomes. This may be because the food environment has a limited impact on shopping behaviors, or because households are not as reliant on supermarkets as we assume. However, our understanding of how households shop for food, especially when considering the use of both food at home (FAH) retailers, such as supermarkets, and away from home retailers (FAFH), such as restaurants, is limited. Thus, understanding how households shop for food is a necessary first step when developing programs to modify food purchasing behavior. Methods K-means cluster analysis was used to identify weekly food shopping trip patterns based on the percentage of trips to FAH and FAFH retailers in the 2013 Food Acquisition and Purchase Survey (FoodAPS) dataset (n = 4665 households). Multinomial logistic regression was used to examine the relationship between shopping trip patterns, household and food environment characteristics. Results Three patterns emerged: primarily supermarket, primarily supercenter, or mix (i.e. no dominant retailer type, but high FAFH use). Households with incomes below 185% of the federal poverty line were evenly divided between patterns that rely primarily on FAH retailers, and the mix pattern. While nearly 70% of households with incomes above 185% of the federal poverty line are in the mix cluster. Supermarket and superstore availability significantly influenced the likelihood of belonging to those clusters respectively, while having a child, higher income, and attitudes towards healthy meal preparation time or taste significantly influenced the likelihood of belonging to the mix cluster. Conclusion Although lower-income households are more likely to rely primarily on FAH retailers, household’s, regardless of income, that primarily utilize FAH retailers show a strong preference for either superstores or supermarkets suggesting a need for interventions to reach both retailer types. However, altering the food environment alone may not be sufficient to discourage use of FAFH retailers as households relying on FAFH retailers are significantly influenced by meal preparation time and healthy food taste.

BackgroundFamily caregivers are more likely to experience insomnia relative to noncaregivers but have significant barriers to accessing gold standard cognitive behavioral therapy for insomnia treatment. Delivering interventions to caregivers through the internet may help increase access to care, particularly among higher-intensity caregivers who provide assistance with multiple care tasks over many hours per week. Although there are existing internet interventions that have been thoroughly studied and demonstrated as effective in the general population, the extent to which these interventions may be effective for caregivers without tailoring to address this population’s unique psychosocial needs has not been studied. ObjectiveThe goal of this trial is to determine what tailoring may be necessary for which caregivers to ensure they receive optimal benefit from an existing evidence-based, internet-delivered cognitive behavioral therapy for insomnia program named Sleep Healthy Using the Internet (SHUTi). Specifically, we will test the association between caregivers’ engagement with SHUTi and their caregiving context characteristics (ie, caregiving strain, self-efficacy, and guilt) and environment (ie, proximity to care recipient; functional status, cognitive status, and problem behavior of care recipient; and type of care provided). Among caregivers using the program, we will also test the associations between change in known treatment mechanisms (sleep beliefs and sleep locus of control) and caregiving context factors. MethodsA total of 100 higher-intensity caregivers with significant insomnia symptoms will be recruited from across the United States to receive access to SHUTi in an open-label trial with mixed methods preassessments and postassessments. At postassessment (9 weeks following preassessment completion), participants will be categorized according to their engagement with the program (nonusers, incomplete users, or complete users). Study analyses will address 3 specific aims: to examine the association between caregivers’ engagement with SHUTi and their caregiving context (aim 1a); to describe caregivers’ barriers to and motivations for SHUTi engagement from open-ended survey responses (aim 1b); and among caregivers using SHUTi, to determine whether cognitive mechanisms of change targeted by SHUTi are associated with differences in caregiving context (aim 2). ResultsInstitutional review board approvals have been received. Data collection is anticipated to begin in December 2021 and is expected to be completed in 2023. ConclusionsFindings will inform the next research steps for tailoring and testing SHUTi for optimal impact and reach among caregivers. Beyond implication to the SHUTi program, the findings will be translatable across intervention programs and will hold significant promise to reduce inefficiencies in developing digital health interventions for caregivers while also increasing their impact and reach for this underserved population. Trial RegistrationClinicalTrials.gov; NCT04986904; https://clinicaltrials.gov/ct2/show/NCT04986904?term=NCT04986904 International Registered Report Identifier (IRRID)PRR1-10.2196/34792

Background The systemic inflammation response index (SIRI), a novel and cost-effective serum biomarker, is associated with prognosis in patients with cancer. However, the prognostic value of the SIRI in cancer remains unclear. This study aimed to evaluate the potential role of the SIRI as a prognostic indicator in cancer. Methods Reports in which the prognostic value of the SIRI in cancer was evaluated were retrieved from electronic databases. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to evaluate the prognostic significance of the SIRI. The odds ratio (OR) was also calculated to explore the association between the SIRI and clinicopathological features. Results This study included 30 retrospective studies with 38 cohorts and 10 754 cases. The meta-analysis indicated that a high SIRI was associated with short overall survival (OS) (HR = 2.04, 95% CI = 1.82–2.29, P < .001) and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS) (HR = 2.08, 95% CI = 1.84–2.34, P < .001). Subgroup analysis showed that the prognostic value of the SIRI was significant in all kinds of cancer included. Moreover, the SIRI was significantly correlated with sex, tumor size, T stage, N stage, TNM stage, and lymphovascular invasion. Conclusion The pretreatment SIRI could be a promising universal prognostic indicator in cancer.

Background: Low caregiver health literacy (HL) is related to increased obesity risk for their children. Teach-Back and Teach-to-Goal (TB/TTG) are strategies that may improve comprehension of key concepts for people who have low HL but have yet to be examined in the context of childhood obesity treatment. Objective: This study evaluated TB/TTG strategies integrated within support calls delivered to caregivers as part of a 3-month childhood obesity intervention. Methods: Ninety-four caregivers (60% Black, 42% high school education or less, 53% with income ≤$29,999, and 34% low HL) with overweight/obese children age 8 to 12 years enrolled in a childhood obesity intervention. Caregiver HL was assessed at baseline using the Newest Vital Sign and caregivers were dichotomized to low and adequate HL groups for analyses. Caregivers received 6 bi-weekly support calls that alternated with in-person, family sessions. Call completion rates, comprehension of key content (correct responses on TB/TTG questions), and satisfaction with support calls were evaluated. Qualitative information on call satisfaction was gathered at the 3-month time point. Key Results: Average completion rate across all calls was 62% with a mean call time of 26 minutes (no significant difference between HL groups). Caregivers had an average score of 0.90 out of 1 when evaluating overall call comprehension by scoring TB/TTG performance. Content comprehension in calls 1, 3, and 4 was significantly higher among caregivers with adequate HL relative to low HL (p < .1). Caregivers from both HL groups felt satisfied with calls [9.1 (2.0)/10-point scale] and agreed that calls helped them learn class material better [8.1 (2.7)]. Qualitatively, caregivers provided 81 (75%) positive responses (e.g., good content) and 27 (25%) negative responses (e.g., too lengthy) regarding the support calls. Conclusions: Support calls using TB/TTG strategies were feasible, well received, and should be considered for incorporation into childhood obesity interventions. [HLRP: Health Literacy Research and Practice. 2021;5(3):e208–e217.] Plain Language Summary: This study evaluated support calls that used Teach-Back and Teach-to-Goal health literacy strategies as part of a childhood obesity treatment trial. Support calls were well accepted and facilitated comprehension of the key learning objectives in caregivers, regardless of health literacy level. These strategies should be considered for incorporation into childhood obesity treatment interventions to increase uptake of main concepts.

Abstract Background Previous studies have associated elevated mortality risk in central Appalachia with coal-mining activities, but few have explored how different non-coal factors influence the association within each county. Consequently, there is a knowledge gap in identifying effective ways to address health disparities in coal-mining counties. To specifically address this knowledge gap, this study estimated the effect of living in a coal-mining county on non-malignant respiratory diseases (NMRD) mortality, and defined this as “coal-county effect.” We also investigated what factors may accentuate or attenuate the coal-county effect. Methods An ecological epidemiology protocol was designed to observe the characteristics of three populations and to identify the effects of coal-mining on community health. Records for seven coal-mining counties (n = 19,692) were obtained with approvals from the Virginia Department of Health Office of Vital Statistics for the years 2005 to 2012. Also requested were records from three adjacent coal counties (n = 10,425) to provide a geographic comparison. For a baseline comparison, records were requested for eleven tobacco-producing counties (n = 27,800). We analyzed the association of 57,917 individual mortality records in Virginia with coal-mining county residency, county-level socioeconomic status, health access, behavioral risk factors, and coal production. The development of a two-level hierarchical model allowed the coal-county effect to vary by county-level characteristics. Wald tests detected sets of significant factors explaining the variation of impacts across counties. Furthermore, to illustrate how the model estimations help explain health disparities, two coal-mining county case studies were presented. Results The main result revealed that coal-mining county residency increased the probability of dying from NMRD. The coal-county effect was accentuated by surface coal mining, high smoking rates, decreasing health insurance coverage, and a shortage of doctors. In Virginia coal-mining regions, the average coal-county effect increased by 147% (p-value

Abstract Background To describe the identification, adaptation, and testing of an evidence-based pediatric weight management program for a health disparate community. Methods A community advisory board (CAB) of decision-makers and staff from local health care, public health, and recreation organizations engaged with academic partners to select an evidence-based program (EBP) for local implementation. Three EBPs were identified (Traffic Light, Bright Bodies, Golan and colleagues Home Environmental Model) and each EBP was rated on program characteristics, implementation and adaptation, and adoptability. Following selection of the EBP that was rated highest, the POPS-CAB made adaptations based on the program principles described in peer-reviewed publications. The adapted intervention, iChoose, was then pilot tested in 3 iterative phases delivered initially by research partners, then co-delivered by research and community partners, then delivered by community partners. The RE-AIM framework was used to plan and evaluate the iChoose intervention across all waves with assessments at baseline, post program (3 months), and follow-up (6 months). Results Bright Bodies rated highest on program characteristics and adoptability (p’s

Under the background of modern industrial processing and production, the sintering furnace's temperature control system is researched to achieve intelligent smelting and reduce energy consumption. First, the specific application and implementation of edge computing in industrial processing and production are analyzed. The industrial processing and production intelligent equipment based on edge computing includes the equipment layer, the edge layer, and the cloud platform layer. This architecture improves the operating efficiency of the intelligent control system. Then, the sintering furnace in the metallurgical industry is taken as an example. The sintering furnace connects powder material particles at high temperatures; thus, the core temperature control system is investigated. Under the actual sintering furnace engineering design, the Distributed Control System (DCS) is used as the basis of sintering furnace temperature control, and the Programmable Logic Controller (PLC) is adopted to reduce the electrical wiring and switch contacts. The hardware circuit of DCS is designed; on this basis, an embedded operating system with excellent performance is transplanted according to functional requirements. The final DCS-based temperature control system is applied to actual monitoring. The real-time temperature of the upper, middle, and lower currents of 1# sintering furnace at a particular point is measured to be 56.95°C, 56.58°C, and 57.2°C, respectively. The real-time temperature of the upper, middle, and lower currents of 2# sintering furnaces at a particular point is measured to be 144.7°C, 143.8°C, and 144.0°C, respectively. Overall, the temperature control deviation of the three currents of the two sintering furnaces stays in the controllable range. An expert system based on fuzzy logic in the fault diagnosis system can comprehensively predict the situation of the sintering furnaces. The prediction results of the sintering furnace's faults are closer to the actual situation compared with the fault diagnosis method based on the Backpropagation (BP) neural network. The designed system makes up for the shortcomings of the sintering furnace's traditional temperature control systems and can control the temperature of the sintering furnace intelligently and scientifically. Besides, it can diagnose equipment faults timely and efficiently, thereby improving the sintering efficiency.

Abstract Background Although reducing sugar-sweetened beverage (SSB) intake is an important behavioral strategy to improve health, no known SSB-focused behavioral trial has examined maintenance of SSB behaviors after an initial reduction. Guided by the RE-AIM framework, this study examines 6–18 month and 0–18 month individual-level maintenance outcomes from an SSB reduction trial conducted in a medically-underserved, rural Appalachia region of Virginia. Reach and implementation indicators are also reported. Methods Following completion of a 6-month, multi-component, behavioral RCT to reduce SSB intake (SIPsmartER condition vs. comparison condition), participants were further randomized to one of three 12-month maintenance conditions. Each condition included monthly telephone calls, but varied in mode and content: 1) interactive voice response (IVR) behavior support, 2) human-delivered behavior support, or 3) IVR control condition. Assessments included the Beverage Intake Questionnaire (BEVQ-15), weight, BMI, and quality of life. Call completion rates and costs were tracked. Analysis included descriptive statistics and multilevel mixed-effects linear regression models using intent-to-treat procedures. Results Of 301 subjects enrolled in the 6-month RCT, 242 (80%) were randomized into the maintenance phase and 235 (78%) included in the analyses. SIPsmartER participants maintained significant 0–18 month decreases in SSB. For SSB, weight, BMI and quality of life, there were no significant 6–18 month changes among SIPsmartER participants, indicating post-program maintenance. The IVR-behavior participants reported greater reductions in SSB kcals/day during the 6–18 month maintenance phase, compared to the IVR control participants (− 98 SSB kcals/day, 95% CI = − 196, − 0.55, p

This community-based participatory research (CBPR) project used a collaborative process to develop a culturally relevant workbook for parents of overweight children. We followed a mixed methods iterative process to assess clear communication using a CBPR approach. Materials were evaluated using readability tests, the Clear Communication Index (CCI), and the Suitability Assessment of Materials (SAM). In addition, we used surveys and focus groups to investigate parents’ perceptions and gather feedback from delivery staff using the workbook. While workbook materials maintained adequate grade reading levels, our iterative process and the use of CCI and SAM led to significant improvements in (a) clearly communicating the objectives of the program, (b) being culturally relevant, and (c) reaching a high satisfaction among users. These findings suggest that evaluative measures for written materials should move beyond readability and need to account for level of clarity and cultural appropriateness of messages. Furthermore, we found that that an iterative process to intervention’s material development using clear communication strategies while involving community members, parents, and research partners can lead to workbook materials that are culturally relevant to the target audience, and better communicate program objectives. Finally, this is a potentially generalizable process for improving clear communication of written health information materials.

The recently developed Healthy Beverage Index (HBI) was designed to evaluate overall beverage intake quality (including total fluid consumption and beverage calories), yet no known intervention studies have assessed longitudinal changes to the HBI. The objective of this investigation was to assess changes in HBI scores in response to a sugar-sweetened beverage (SSB) reduction trial as compared to a physical activity comparison group. Participants were enrolled into a six-month, community-based, controlled behavioral trial and randomized into either a SSB reduction group (SIPsmartER) or a physical activity group (MoveMore). Correlations and multilevel mixed-effects linear regression with intention-to-treat analyses are presented. Total HBI score significantly increased for SIPsmartER (n = 149) (mean increase = 7.5 points (5.4, 9.7), p ≤ 0.001) and MoveMore (n = 143) (mean increase = 3.4 points (1.6, 5.2), p ≤ 0.001) participants, with a significant between group effect (p ≤ 0.05), over the six-month intervention. Other significant changes in HBI components for SIPsmartER included increased SSB and total beverage calorie scores, and decreased low-fat milk and diet soda scores. Changes in total HBI scores were significantly correlated with changes in total Healthy Eating Index-2010 scores (r = 0.15, p ≤ 0.01). Our findings suggest that individual HBI component scores, beyond the SSB component, are influenced by intervention strategies that primarily focus on SSB reduction.

The microstructural evolution and properties of an Al-Cu-Li alloy with Mg and Zn microalloying (Al-3.5Cu-1.5Li-0.5Mg-0.4Zn-0.3Mn-0.12Zr-0.06Ti) ingot subjected to homogenization (second-step annealing at 500 °C for 24 h following first-step annealing at 400 °C for 8 h) were investigated. Mg-Zn atom clusters were enriched at the end of dendrites as well as low-melting eutectic phases such as S (Al2CuMg), T2 (Al6CuLi3), TB (Al7.5Cu4Li) and T1 (Al2CuLi) in the as-cast alloy. During homogenization, Mg-Zn atom clusters diffused from the segregation to the vacancies, leading to the dissolution of the low-melting eutectic phases. Not only Al3Zr particles were observed at 500 °C, but more fine and uniform spherical dispersoids appeared, which were assumed as Al3(ZrxTiyLi1−x−y). Mg and Zn microalloying can promoted the nucleation of Al3Zr and Al3(ZrxTiyLi1−x−y) dispersoids, as well as T (Al20Cu2Mn3) phases, which all inhibited recrystallization effectively and improve the uniformity of the grains due to the strong pinning effect. The yield ratio was decreased from 0.81 to 0.52 with the yield strength decreased from 172 MPa to 61 MPa, which showed better plastic deformation ability of the alloy subjected to homogenization. In addition, the dissolution of low-melting eutectic phases and formation of Al3(ZrxTiyLi1−x−y) dispersoids resulted in the significant improvement on thermal stability.

Previous studies have found a strong relationship between food-away-from-home expenditures and television viewing, and children's diet. This study revisits this issue by examining the impact of household fast food expenditures and children's television viewing on children's dietary quality. Results indicate that both factors have statistically significant and negative effects. However, the elasticities of children's diet quality with respect to both factors are quite inelastic. Results also suggest that the effects of these two factors differ between children younger than 11 years old and children at least 11 years old. Relevant policy implications are discussed.

Few data assessing non-nutritive sweetener (NNS) intake are available, especially within rural, health-disparate populations, where obesity and related co-morbidities are prevalent. The objective of this study is to characterize NNS intake for this population and examine the variance in demographics, cardio-metabolic outcomes, and dietary intake between NNS consumers and non-consumers. A cross-sectional sample (n = 301) of Virginian adults from a randomized controlled trial (data collected from 2012 to 2014) targeting sugar-sweetened beverage (SSB) intake completed three 24-h dietary recalls, and demographics and cardio-metabolic measures were assessed. The frequency, types, and sources of NNS consumption were identified. Thirty-three percent of participants reported consuming NNS (n = 100). Sucralose was the largest contributor of mean daily NNS intake by weight (mg), followed by aspartame, acesulfame potassium, and saccharin. NNS in tabletop sweeteners, diet tea, and diet soda were the top contributors to absolute NNS intake. The most frequently consumed NNS sources were diet sodas, juice drinks, and tabletop sweeteners. Although mean body mass index (BMI) was greater for NNS consumers, they demonstrated significantly lower food, beverage, and SSB caloric intake and energy density, and higher overall dietary quality. It remains unclear whether NNS use plays a role in exacerbating weight gain. NNS consumers in this sample may have switched from drinking predominantly SSB to drinking some NNS beverages in an effort to cope with weight gain. Future studies should explore motivations for NNS use across a variety of weight and health categories.

Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress‐related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress. A screen of lysosome‐related genes revealed that the expression of the mucolipin 1 gene (Mcoln1; protein: mucolipin TRP channel 1) is decreased in susceptible mice and depressed patients. Astrocyte‐specific knockout of mucolipin TRP channel 1 (TRPML1) induced depressive‐like behaviors by inhibiting lysosomal exocytosis‐mediated adenosine 5′‐triphosphate (ATP) release. Furthermore, this stress response of astrocytic lysosomes is mediated by the transcription factor EB (TFEB), and overexpression of TRPML1 rescued depressive‐like behaviors induced by astrocyte‐specific knockout of TFEB. Collectively, these findings reveal a lysosomal stress‐sensing signaling pathway contributing to the development of depression and identify the lysosome as a potential target organelle for antidepressants. [ABSTRACT FROM AUTHOR]

Major depressive disorder is a common and devastating psychiatric disease, and the prevalence and burden are substantially increasing worldwide. Multiple studies of depression patients have implicated glucose metabolic dysfunction in the pathophysiology of depression. However, the molecular mechanisms by which glucose and related metabolic pathways modulate depressive-like behaviors are largely uncharacterized. Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) is a glucose metabolite with pivotal functions as a donor molecule for O-GlcNAcylation. O-GlcNAc transferase (OGT), a key enzyme in protein O-GlcNAcylation, catalyzes protein posttranslational modification by O-GlcNAc and acts as a stress sensor. Here, we show that Ogt mRNA was increased in depression patients and that astroglial OGT expression was specifically upregulated in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social-defeat stress. The selective deletion of astrocytic OGT resulted in antidepressant-like effects, and moreover, astrocytic OGT in the mPFC bidirectionally regulated vulnerability to social stress. Furthermore, OGT modulated glutamatergic synaptic transmission through O-GlcNAcylation of glutamate transporter-1 (GLT-1) in astrocytes. OGT astrocyte-specific knockout preserved the neuronal morphology atrophy and [Ca.sup.2+] activity deficits caused by chronic stress and resulted in antidepressant effects. Our study reveals that astrocytic OGT in the mPFC regulates depressive-like behaviors through the O-GlcNAcylation of GLT-1 and could be a potential target for antidepressants., Introduction The lifetime prevalence (~17%), disability (as a leading cause), and socioeconomic burden associated with major depressive disorder (MDD) render it one of the most common and devastating psychiatric illnesses [...]

Background: Cognitive function (CF) deterioration is a pressing concern in geriatric research. This study aimed to explore the relationship between physical activity (PA) and CF in older adults. Methods: This study adopted a dual approach, employing both observational and genetic approaches through data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 and Mendelian Randomization (MR) analysis. For the NHANES component, PA levels were evaluated using the Global Physical Activity Questionnaire, and CF was assessed via standardized tests. Multivariate regression, threshold effect analysis, smoothing curve fitting, and subgroup analyses were conducted to examine the association between PA and CF. In parallel, MR methods, using genetic variants as instrumental variables, assessed the causal impact of PA on CF and related conditions such as Alzheimer's disease and dementia. Results: Observational findings from NHANES demonstrated a positive correlation between PA and CF, notably among female participants. The detailed analysis identified specific thresholds of PA that correlate with cognitive enhancements. However, MR results did not support a significant causal relationship between PA and CF or dementia-related outcomes, indicating an absence of a direct genetic basis for the observational associations. Conclusion: Although observational data from NHANES suggest that PA is positively associated with CF in older adults, particularly among women, MR analysis did not confirm these findings as causally related. The discrepancy highlights the complexity of the PA-CF relationship and underscores the need for further research. These results emphasize the potential of PA as a modifiable risk factor for CF, though causal effects remain to be definitively established. [ABSTRACT FROM AUTHOR]

Introduction: Deep learning (DL) models predicting biomarker expression in images of hematoxylin and eosin (H&E)-stained tissues can improve access to multi-marker immunophenotyping, crucial for therapeutic monitoring, biomarker discovery, and personalized treatment development. Conventionally, these models are trained on ground truth cell labels derived from IHC-stained tissue sections adjacent to H&Estained ones, which might be less accurate than labels from the same section. Although many such DL models have been developed, the impact of ground truth cell label derivation methods on their performance has not been studied. Methodology: In this study, we assess the impact of cell label derivation on H&E model performance, with CD3+ T-cells in lung cancer tissues as a proof-ofconcept. We compare two Pix2Pix generative adversarial network (P2P-GAN)- based virtual staining models: one trained with cell labels obtained from the same tissue section as the H&E-stained section (the 'same-section' model) and one trained on cell labels from an adjacent tissue section (the 'serial-section' model). Results: We show that the same-section model exhibited significantly improved prediction performance compared to the 'serial-section' model. Furthermore, the same-section model outperformed the serial-section model in stratifying lung cancer patients within a public lung cancer cohort based on survival outcomes, demonstrating its potential clinical utility. Discussion: Collectively, our findings suggest that employing ground truth cell labels obtained through the same-section approach boosts immunophenotyping DL solutions. [ABSTRACT FROM AUTHOR]