A qualitative exploration of barriers, facilitators and best practices for implementing environmental sustainability standards and reducing food waste in veterans affairs hospitals.

BACKGROUND: To improve the healthfulness of foods offered while accelerating the use of environmental sustainability practices, it is important to engage hospital food service operators in the adoption of such practices. The purpose of this study was to explore barriers, facilitators and best practices for implementing environmental sustainability standards in food service among veterans affairs (VA) hospitals in the United States. METHODS: We conducted an online survey with 14 VA hospital food service directors and then 11 qualitative interviews. The survey assessed motivations for initiating sustainability standards and included a self-rating of implementation for each of five standards: increasing plant-forward dishes, procuring and serving sustainable foods that meet organic/fair trade and other certifications, procuring and serving locally produced foods, reducing food waste and reducing energy consumption. Interviews were transcribed verbatim. Qualitative analysis, including coding of themes and subthemes, was conducted by two coders to determine barriers, facilitators and best practices for each of these five standards. Quantitative methods (counts and frequencies) were used to analyse the survey data. RESULTS: Participants had an average of 5 years of experience implementing sustainability standards. The top three motivators cited were reducing food waste, serving healthier foods and increasing efficiency or cost savings. Barriers revolved around patient preferences, contractual difficulties and costs related to reducing waste. Facilitators included taste testing new recipes that include more sustainable food options and easy access to sustainable products from the prime vendor. Best practices included making familiar dishes plant-forward and plate waste studies to prevent overproduction. CONCLUSIONS: Although there were many barriers to implementation, food service directors had solutions for overcoming challenges and implementing food service sustainability standards, which can be tested in future sustainability initiatives.

Household Food Sourcing Patterns and Their Associations with Food Insecurity in Appalachian Ohio.

BACKGROUND: Households experiencing food insecurity may use dynamic strategies to meet food needs. Yet, the relationship between household food sourcing behaviors and food security, particularly in rural settings, is understudied. OBJECTIVE: To identify food sourcing patterns and their associations with food insecurity among households in rural Appalachian Ohio during the COVID-19 pandemic. DESIGN: Survey data were collected from a cohort of households in Athens County, Ohio in July 2020, October 2020, January 2021, and April 2021. PARTICIPANTS/SETTING: The sample included 663 households with household food sourcing and food security information for ≥1 survey wave. MAIN OUTCOME MEASURES: Household food sourcing patterns. Households reported the frequency with which they obtained food from various retailers and charitable sources, classified as supercenters, supermarkets, convenience stores, farmers' markets, or charitable sources. STATISTICAL ANALYSES: Principal component analysis was used to identify food sourcing patterns. Linear mixed models were used to assess changes in food sourcing behaviors over the study period and to determine whether food sourcing behaviors differed according to food security status. RESULTS: Two patterns were identified: 1) Convenience Stores and Charitable Food, 2) Supermarkets and Farmers' Markets, not Supercenters. Relative to July 2020, alignment of households' food sourcing behaviors with the "Supermarkets and Farmers' Markets, not Supercenters" pattern was higher in October 2020 (ß=0.07; 95% CI: 0.02, 0.12) and alignment with the "Convenience Stores and Charitable Food" pattern was lower in April 2021 (ß=-0.06; 95% CI: -0.11, -0.02). Compared to food-secure households, food sourcing behaviors of food-insecure households were more closely aligned with the "Convenience Stores and Charitable Food" pattern (ß=0.07; 95% CI: 0.00, 0.13); no statistically significant difference in scores was observed for the "Supermarkets and Farmers' Markets, not Supercenters" pattern (ß=-0.07; 95% CI: -0.15, 0.02). CONCLUSIONS: These findings support efforts to increase access to healthy, affordable options at venues where food-insecure households may be likely to obtain food, such as convenience stores and charitable sources.

Soluble immune checkpoints: implications for cancer prognosis and response to immune checkpoint therapy and conventional therapies.

Longitudinal sampling of tumor tissue from patients with solid cancers, aside from melanoma and a few other cases, is often unfeasible, and thus may not capture the plasticity of interactions between the tumor and immune system under selective pressure of a given therapy. Peripheral blood analyses provide salient information about the human peripheral immunome while offering technical and practical advantages over traditional tumor biopsies, and should be utilized where possible alongside interrogation of the tumor. Some common blood-based biomarkers used to study the immune response include immune cell subsets, circulating tumor DNA, and protein analytes such as cytokines. With the recent explosion of immune checkpoint inhibitors (ICI) as a modality of treatment in multiple cancer types, soluble immune checkpoints have become a relevant area of investigation for peripheral immune-based biomarkers. However, the exact functions of soluble immune checkpoints and their roles in cancer for the most part remain unclear. This review discusses current literature on the production, function, and expression of nine soluble immune checkpoints - sPD-L1, sPD-1, sCTLA4, sCD80, sTIM3, sLAG3, sB7-H3, sBTLA, and sHVEM - in patients with solid tumors, and explores their role as biomarkers of response to ICI as well as to conventional therapies (chemotherapy, radiotherapy, targeted therapy, and surgery) in cancer patients.

Evidence for Criterion-Related Validity of Pressure-Mediated Reflection Spectroscopy for Approximating Fruit and Vegetable Consumption among Preschool Children.

BACKGROUND: Skin carotenoids are a valid biomarker for approximating fruit and vegetable consumption (FVC). Veggie Meter® (VM®, Longevity Link Corp.) is a pressure-mediated reflection spectroscopy (RS)-based device that allows for noninvasive and rapid assessment of skin-carotenoid score (SCS) in adults and children. Although VM® is established as a valid tool to measure FVC in adults, there is limited research supporting the validity evidence of the VM® to approximate FVC among preschool children. OBJECTIVE: The current study aims to assess evidence supporting the criterion-related validity of RS-based SCS for approximating FVC among preschool children (3-5-y old). METHODS: We collected cross-sectional data from typically developing preschool children (n = 136) attending the Child and Adult Care Food Program-participating family child care home settings (FCCHs) (n = 46) in Nebraska. Research team members collected children's height and weight to calculate body mass index; and measured children's SCS using the VM®. Children's FVC in FCCHs were collected using dietary observation. In addition, parents (n = 89) completed a shortened food frequency questionnaire to report children's FVC at home. Kendall's Tau (τ) correlation tests were conducted to measure the association between children's SCS with FVC in FCCHs and with parent-reported total fruit and vegetable (FV) frequency scores. RESULTS: Children's SCS were significantly correlated with their mean FVC in FCCHs, τ = 0.14 (P = 0.02), total provitamin A carotenoids intake in FCCHs, τ = 0.19 (P < 0.001), and with parent-reported total FV frequency score, τ = 0.16 (P = 0.04). CONCLUSION: The correlation coefficients in this study are comparable with results from a meta-analysis examining associations between FVC and SCS in 7-10-y-old children (r = 0.20). Thus, evidence suggests that RS offers a potentially valid, objective, and feasible method to assess preschool children's total FVC in multiple settings, especially in conjunction with other dietary assessment tools.

Examining Potential Modifiers of Human Skin and Plasma Carotenoid Responses in a Randomized Trial of a Carotenoid-Containing Juice Intervention.

BACKGROUND: Skin carotenoid measurements are emerging as a valid and reliable indicator of fruit and vegetable intake and carotenoid intake. However, little is known about the extent to which skin carotenoid responsivity to dietary changes differs based on demographic and physiologic characteristics. OBJECTIVES: This study examined potential effect modifiers of skin carotenoid and plasma carotenoid responses to a carotenoid-rich juice intervention. METHODS: We leveraged data from 2 arms of a 3-site randomized controlled trial of a carotenoid-containing juice intervention (moderate dose = 6 ounces juice, 4 mg total carotenoids/d, high dose = 12 ounces juice, 8 mg total carotenoids/d) (n = 106) to examine effect modification by age, self-categorized race/ethnicity, biological sex, baseline body fat, body mass index, skin melanin, skin hemoglobin, skin hemoglobin saturation, skin coloration, sun exposure, and baseline intake of carotenoids from foods. Skin carotenoid concentrations were assessed using pressure-mediated reflection spectroscopy (Veggie Meter), and plasma carotenoid concentrations were measured using high-performance liquid chromatography. RESULTS: In bivariate analyses, among the high-dose group (8 mg/d), those of older age had lower skin carotenoid responsiveness than their younger counterparts, and those with greater hemoglobin saturation and lighter skin had higher skin carotenoid score responsiveness. In the moderate-dose group (4 mg/d), participants from one site had greater plasma carotenoid responsiveness than those from other sites. In multivariate analyses, participants with higher baseline skin carotenoids had smaller skin carotenoid responses to both moderate and high doses. CONCLUSIONS: Changes in skin carotenoid scores in response to interventions to increase fruit and vegetable intake should be interpreted in the context of baseline skin carotenoid scores, but other variables (e.g., self-categorized race/ethnicity, biological sex, baseline body fat, body mass index, skin melanin, and sun exposure) do not significantly modify the effect of carotenoid intake on changes in skin carotenoid scores. This trial was registered at clinicaltrials.gov as NCT04056624.

A Mixed-Methods Study to Evaluate the Feasibility and Acceptability of Implementing an Electronic Health Record Social Determinants of Health Screening Instrument into Routine Clinical Oncology Practice.

BACKGROUND: Routine screening for social determinants of health (SDOH) in the outpatient oncology setting is uncommon. The primary goal of this study was to prospectively evaluate the feasibility and acceptability of implementing an electronic health record (EHR) SDOH screening instrument into routine, clinical, oncology practice. METHODS: Adult patients with newly diagnosed gastrointestinal cancer presenting to a regional cancer center (November 2020 to July 2021) were eligible. Based on the consolidated framework for implementation research, feasibility measures included screening completion, median clinic visit time, and acceptability by the inter-professional care team and patients as measured by semistructured, qualitative interviews and surveys. Secondary outcomes included SDOH needs identified. RESULTS: Of 137 eligible patients, 112 (81.8%) were screened for SDOH. Demographics of the cohort included: 41.1% black (n = 46), 48.2% rural (n = 54), 4.5% uninsured (n = 5), and 6.3% Medicaid-insured (n = 7) patients. Median visit time was 97 min (95% CI 70-107 min) before and 100 min after implementation (95% CI 75-119 min; p = 0.95). In total, 95.5% (n = 107) reported at least one SDOH need. Clinicians (7/10) reported that SDOH screening was not disruptive and were supportive of ongoing use. Patients (10/10) found the screening acceptable. Screening staff (5/5) reported workflow barriers. Patients and staff also recommended revision of specific instrument questions. CONCLUSIONS: Routine collection of SDOH in an outpatient oncology setting using an EHR instrument is feasible and does not result in increased visit time for patients or clinicians. However, staff perceptions of clinic workflow disruption were reported. Further investigation to determine whether standardized SDOH assessment can improve cancer care delivery and outcomes is ongoing.

A Systematic Literature Review of Nutrition Interventions Implemented to Address Food Insecurity as a Social Determinant of Health.

BACKGROUND: Policy initiatives have provided funding for non-acute nutrition interventions to address food insecurity as a social determinant of health, but more research is needed to understand the outcomes of these initiatives in order to determine the areas of highest impact. Therefore, the purpose of this systematic review was to evaluate the outcomes that were assessed in three nutrition interventions (produce prescription programs, medically tailored meals, and community supported agriculture) that aim to address food insecurity as a social determinant of health, and this was undertaken in order to identify future areas of study that can heighten impact. METHODS: This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria. A list of search terms and keywords were compiled by the research team. A Boolean search was conducted from 1 January 2000 to 1 January 2023 in the PubMed advanced search database. RESULTS: A total of 1015 articles were initially pulled from the PubMed database, and, after a screening process, 21 articles were included in our review. Nineteen of the articles focused on adult populations or families and two focused on children. The main outcomes assessed were changes in self-reported dietary intake, while a few of the articles addressed feasibility and cost-related outcomes. CONCLUSIONS: More research is needed to assess whether nutritional interventions to address food insecurity as a social determinant of health are feasible and more cost effective in the long term. Additionally, more work should be conducted in pediatric populations, which could have a robust return on investment in terms of both healthcare utilization and healthcare expenditure.

Associations between food and beverage purchases and skin carotenoids among diverse small food retail store customers.

OBJECTIVE: To determine if customer purchases at small food stores are associated with healthfulness of the diet as approximated by skin carotenoids. DESIGN: This is a cross-sectional survey of customers in small food stores regarding demographics and food purchases. Food and beverage purchases were classified as 'healthy' or 'non-healthy' and 'carotenoid' v. 'non-carotenoid' using a systematic classification scheme. Fruit and vegetable intake was objectively assessed using a non-invasive device to measure skin carotenoids. Associations between variables of interest were examined using Pearson's correlation coefficients, t tests and multiple linear regression analyses. SETTING: Twenty-two small food retail stores in rural (n 7 stores) and urban (n 15) areas of North Carolina. PARTICIPANTS: Customers of small food stores. RESULTS: Of study participants (n 1086), 55·1 % were male, 60·0 % were African American/Black and 4·2 % were Hispanic, with a mean age of 43·5 years. Overall, 36 % purchased at least one healthy item, and 7·6 % of participants purchased a carotenoid-containing food/beverage. Healthy foods and beverages purchased included produce, lean meats, 100 % juices, plain popcorn, plain nuts, milk and yogurt. Unhealthy items included non-100 % juices, crackers, chips, candy, cakes and donuts. Purchase of a healthy or carotenoid-containing item was positively associated with skin carotenoid scores (P = 0·002 and 0·006, respectively). CONCLUSIONS: A relatively small proportion of customers purchased any healthy or carotenoid-containing foods and beverages, and those who did purchase healthy options had higher skin carotenoid scores. Future research should confirm these findings in different populations.

Cost analysis and cost effectiveness of a subsidized community supported agriculture intervention for low-income families.

BACKGROUND: The food system has a dynamic influence on disparities in food security and diet-related chronic disease. Community supported agriculture (CSA) programs, in which households receive weekly shares of produce from a local farmer during the growing season, have been examined as a possible food systems-based approach for improving diet and health outcomes. The purpose of this study was to estimate the cost of implementing and participating in a multi-component subsidized community supported agriculture intervention and calculate cost-effectiveness based on diet and food security impacts. METHODS: Using data from the Farm Fresh Foods for Healthy Kids (F3HK) randomized controlled trial in New York, North Carolina, Vermont, and Washington (n = 305; 2016-2018), we estimated programmatic and participant costs and calculated incremental cost-effectiveness ratios (ICERs) for caregivers' daily fruit and vegetable (FV) intake, skin carotenoids, and household food security from program and societal perspectives. RESULTS: F3HK cost $2,439 per household annually ($1,884 in implementation-related expenses and $555 in participant-incurred costs). ICERs ranged from $1,507 to $2,439 per cup increase in caregiver's FV intake (depending on perspective, setting, and inclusion of juice); from $502 to $739 per one thousand unit increase in skin carotenoid score; and from $2,271 to $3,137 per household shifted out of food insecurity. CONCLUSIONS: Given the known public health, healthcare, and economic consequences of insufficient FV intake and living in a food insecure household, the costs incurred to support these positive shifts in individual- and household-level outcomes via a F3HK-like intervention may be deemed by stakeholders as a reasonable investment. This work helps to advance a critical body of literature on the cost-effectiveness of subsidized CSAs and other economic and food system interventions for the sake of evidence-based allocation of public health resources. TRIAL REGISTRATION: ClinicalTrials.gov. NCT02770196. Registered 5 April 2016. Retrospectively registered. https://www. CLINICALTRIALS: gov/ct2/show/NCT02770196 .

Fruit and Vegetable Preparation Changes During and After Cost-Offset Community-Supported Agriculture Plus Nutrition Education.

OBJECTIVE: Inadequate consumption of fruits and vegetables (FV) can negatively impact health. Cost-offset, or subsidized, community-supported agriculture (CO-CSA) may change FV preparation behaviors among caregivers in low-income households. We assessed changes in FV preparation frequency and methods during and after participation in a CO-CSA plus tailored nutrition education intervention. DESIGN: Longitudinal comparison of outcomes at baseline, end of CO-CSA season, and 1 year later. PARTICIPANTS: Caregivers of children aged 2-12 years from households with low income in rural areas of 4 US states (n = 148). INTERVENTION: Summer season, half-price CO-CSA share plus tailored nutrition education classes. Comparison to a control group not included in this analysis. VARIABLES MEASURED: Monthly frequency of preparing 9 FV for children's snacks and 5 vegetables for dinner; use of healthy preparation methods for dinner. ANALYSIS: Repeated measures ANCOVA including state with Bonferroni correction and 95% confidence. RESULTS: At baseline, caregivers prepared fruit for children's snacks and vegetables for dinner almost daily and vegetables for children's snacks every other day. The frequency of total FV preparation and most vegetable varieties increased during the intervention. Increases in total vegetables for snacks, dinner, and leafy greens were maintained 1 year later (n = 107). CONCLUSIONS AND IMPLICATIONS: Community-supported agriculture plus education is a promising approach to sustained increases in vegetable preparation for children's snacks and dinner meals.

Hypercalcemia of malignancy caused by parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumors (PTHrP-PNETs): Case Report.

Parathyroid hormone-related protein (PTHrP) secretion is occasionally detected in various solid tumors such as renal cell carcinoma and lung cancers. It is considered quite rare for neuroendocrine tumors with only few published case reports. We reviewed the current literature and summarized a case report of a patient with metastatic pancreatic neuroendocrine tumor (PNET) presenting with hypercalcemia due to elevation of PTHrP. The patient had histological confirmation of well-differentiated PNET and developed hypercalcemia years after his initial diagnosis. In our case report, evaluation showed intact parathyroid hormone (PTH) in the setting of concomitant elevation of PTHrP. The patient's hypercalcemia and PTHrP levels were improved by using a long-acting somatostatin analogue. In addition, we reviewed the current literature regarding the optimal management of malignant hypercalcemia due to PTHrP-producing PNETs.

Expression of RNA polymerase I catalytic core is influenced by RPA12.

RNA Polymerase I (Pol I) has recently been recognized as a cancer therapeutic target. The activity of this enzyme is essential for ribosome biogenesis and is universally activated in cancers. The enzymatic activity of this multi-subunit complex resides in its catalytic core composed of RPA194, RPA135, and RPA12, a subunit with functions in RNA cleavage, transcription initiation and elongation. Here we explore whether RPA12 influences the regulation of RPA194 in human cancer cells. We use a specific small-molecule Pol I inhibitor BMH-21 that inhibits transcription initiation, elongation and ultimately activates the degradation of Pol I catalytic subunit RPA194. We show that silencing RPA12 causes alterations in the expression and localization of Pol I subunits RPA194 and RPA135. Furthermore, we find that despite these alterations not only does the Pol I core complex between RPA194 and RPA135 remain intact upon RPA12 knockdown, but the transcription of Pol I and its engagement with chromatin remain unaffected. The BMH-21-mediated degradation of RPA194 was independent of RPA12 suggesting that RPA12 affects the basal expression, but not the drug-inducible turnover of RPA194. These studies add to knowledge defining regulatory factors for the expression of this Pol I catalytic subunit.

Systematic Review of Reflection Spectroscopy-Based Skin Carotenoid Assessment in Children.

Assessing children's skin carotenoid score (SCS) using reflection spectroscopy (RS) is a non-invasive, widely used method to approximate fruit and vegetable consumption (FVC). The aims for the current review were to (1) identify distributions of SCS across demographic groups, (2) identify potential non-dietary correlates for RS-based SCS, (3) summarize the validity and reliability of RS-based SCS assessment, and (4) conduct meta-analyses of studies examining the correlation between RS-based SCS with FVC. A literature search in eight databases in June 2021 resulted in 4880 citations and peer-reviewed publications written in English that investigated children's (2-10 years old) SCS using RS. We included 11 studies (intervention = 3, observational = 8). Potential covariates included weight status, ethnicity, seasonal variation, age, sex, and income. Studies reported criterion validity with children's FVC but not with plasma carotenoid. Additionally, no studies reported the reliability of RS-based SCS in children. Among the 726 children included in the meta-analysis, the correlation between RS-based SCS and FVC was r = 0.2 (p < 0.0001). RS-based SCS is a valid method to quantify skin carotenoids for children's FVC estimation with the potential for evaluating nutrition policies and interventions. However, future research should use standardized protocol for using RS and establish how RS-based SCS can translate to the amount of daily FVC in children.

Reflection Spectroscopy-Assessed Skin Carotenoids Are Sensitive to Change in Carotenoid Intake in a 6-Week Randomized Controlled Feeding Trial in a Racially/Ethnically Diverse Sample.

BACKGROUND: Reflection spectroscopy, utilized by the Veggie Meter, is a less-expensive, noninvasive method to quantify skin carotenoids and is a valid approximation of fruit and vegetable (FV) intake. However, it is unknown to what degree Veggie Meter-assessed skin carotenoid score change is responsive to changes in carotenoid intake. OBJECTIVES: This study aimed to evaluate Veggie Meter-assessed skin carotenoid score response in a 6-wk randomized controlled trial of a carotenoid-containing juice to determine whether the Veggie Meter can be used to detect nutritionally relevant changes in carotenoid intake; and to compare skin and plasma carotenoid responses with the 6-wk trial. METHODS: In this 6-wk trial, participants (n = 162) who self-identified as one of 4 US racial/ethnic groups (25% Black, 25% Asian, 27% non-Hispanic White, 23% Hispanic) were randomized to a control group, receiving negligible carotenoids (177 mL apple juice/d), moderate-dose group, receiving 4 mg total carotenoids/d (177 mL orange-carrot juice/d), or high-dose group, receiving 8 mg total carotenoids/d (355 mL orange-carrot juice/d). Skin carotenoid score and plasma total carotenoid concentrations (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, lutein, zeaxanthin) were assessed at baseline, 3 wk, and 6 wk (n = 158 completed the trial). Repeated measures linear models were used to examine skin and plasma carotenoids over time and between groups. RESULTS: At 6 wk, participants in the high-dose and moderate-dose groups had significantly higher mean skin carotenoid scores [414.0 (SD = 100.6) and 369.7 (SD = 100.3), respectively] compared with those in the control group [305.2 (100.5)]. In the high-dose group, there was a 42% change in skin carotenoids from baseline (mean = 290.4) to a 6-wk follow-up (increase of 123, 123/290 = 42.4%). There was a 61% change in the plasma carotenoids in the high-dose group. CONCLUSIONS: The Veggie Meter is sensitive to increases in daily carotenoid intake in diverse racial/ethnic groups over 6 wk. CLINICAL TRIALS REGISTRY NUMBER: This trial was registered at clinicaltrials.gov as ID: NCT04056624. Study URL: https://clinicaltrials.gov/ct2/show/NCT04056624.

Food Insecurity in the Rural United States: An Examination of Struggles and Coping Mechanisms to Feed a Family among Households with a Low-Income.

Households with a low-income in rural places experience disproportionate levels of food insecurity. Further research is needed about the nuances in strategies that households with a low-income in rural areas apply to support food security nationally. This study aimed to understand the barriers and strategies that households with a low-income in rural areas experience to obtain a meal and support food security in the United States. We conducted a qualitative study with semi-structured interviews among 153 primary grocery shoppers with a low-income residing in rural counties. A majority of family's ideal meals included animal-based protein, grains, and vegetables. Main themes included struggles to secure food and coping mechanisms. Ten categories included affordability, adequacy, accommodation, appetite, time, food source coordinating, food resource management, reduced quality, rationing for food, and exceptional desperation. These results can inform public health professionals' efforts when partnering to alleviate food insecurity in rural areas.

Regulation of RNA Polymerase I Stability and Function.

RNA polymerase I is a highly processive enzyme with fast initiation and elongation rates. The structure of Pol I, with its in-built RNA cleavage ability and incorporation of subunits homologous to transcription factors, enables it to quickly and efficiently synthesize the enormous amount of rRNA required for ribosome biogenesis. Each step of Pol I transcription is carefully controlled. However, cancers have highjacked these control points to switch the enzyme, and its transcription, on permanently. While this provides an exceptional benefit to cancer cells, it also creates a potential cancer therapeutic vulnerability. We review the current research on the regulation of Pol I transcription, and we discuss chemical biology efforts to develop new targeted agents against this process. Lastly, we highlight challenges that have arisen from the introduction of agents with promiscuous mechanisms of action and provide examples of agents with specificity and selectivity against Pol I.

Identification of an E3 ligase that targets the catalytic subunit of RNA Polymerase I upon transcription stress.

RNA Polymerase I (Pol I) synthesizes rRNA, which is the first and rate-limiting step in ribosome biogenesis. Factors governing the stability of the polymerase complex are not known. Previous studies characterizing Pol I inhibitor BMH-21 revealed a transcriptional stress-dependent pathway for degradation of the largest subunit of Pol I, RPA194. To identify the E3 ligase(s) involved, we conducted a cell-based RNAi screen for ubiquitin pathway genes. We establish Skp-Cullin-F-box protein complex F-box protein FBXL14 as an E3 ligase for RPA194. We show that FBXL14 binds to RPA194 and mediates RPA194 ubiquitination and degradation in cancer cells treated with BMH-21. Mutation analysis in yeast identified lysines 1150, 1153, and 1156 on Rpa190 relevant for the protein degradation. These results reveal the regulated turnover of Pol I, showing that the stability of the catalytic subunit is controlled by the F-box protein FBXL14 in response to transcription stress.

"Let's Use This Mess to Our Advantage": Calls to Action to Optimize School Nutrition Program beyond the Pandemic.

School nutrition programs mitigate food insecurity and promote healthy eating by offering consistent, nutritious meals to school-aged children in communities across the United States; however, stringent policy guidelines and contextual challenges often limit participation. During COVID-19 school closures, most school nutrition programs remained operational, adapting quickly and innovating to maximize reach. This study describes semi-structured interviews with 23 nutrition directors in North Carolina, which aimed to identify multi-level contextual factors that influenced implementation, as well as ways in which the innovations during COVID-19 could translate to permanent policy and practice change and improve program reach. Interviews were conducted during initial school closures (May-August 2020) and were deductively analyzed using the Social Ecological Model (SEM) and Consolidated Framework for Implementation Research (CFIR). Analysis elicited multiple relevant contextual factors: director characteristics (motivation, leadership style, experience), key implementation stakeholders (internal staff and external partners), inner setting (implementation climate, local leadership engagement, available resources, structural characteristics), and outer setting (state leadership engagement, external policies and incentives). Findings confirm the strength and resilience of program directors and staff, the importance of developing strategies to strengthen external partnerships and emergency preparedness, and strong support from directors for policies offering free meals to all children.