'Acceleration' of the food delivery marketplace: Perspectives of local authority professionals in the North-East of England on temporary COVID regulations.

In January 2021, we assessed the implications of temporary regulations in the United Kingdom allowing pubs and restaurants to operate on a takeaway basis without instigating a change of use. Local authorities (LAs) across the North-East of England were unaware of any data regarding the take-up of these regulations, partially due to ongoing capacity issues; participants also raised health concerns around takeaway use increasing significantly. One year on, we repeated the study aiming to understand the impact of these regulations on the policy and practice of key professional groups. Specifically, we wanted to understand if LAs were still struggling with staff capacity to address the regulations, whether professionals still had public health trepidations, and if any unexpected changes had occurred across the local food environment because of the pandemic. We conversed with 16 public health professionals, planners and environmental health officers across seven LAs throughout the North-East of England via focus groups and interviews. Data collated were analysed via an inductive and semantic, reflexive-thematic approach. Through analysis of the data, three themes were generated and are discussed throughout: popular online delivery services as a mediator to increased takeaway usage; potential long-term health implications and challenges; continued uncertainty regarding the temporary regulations. This paper highlights important changes to local food environments, which public health professionals should be aware of, so they are better equipped to tackle health inequalities across urban and sub-urban areas.

Identification of tax options for high fat, sugar, salt foods for the HEALTHEI Project: a mixed-methods study.

BACKGROUND: The health economic analysis incorporating effects on labour outcomes, households, environment, and inequalities (HEALTHEI) explores which food taxes would have greatest benefits to health, labour, and work outcomes; household expenditure; environmental sustainability; and inequalities within the UK food system. Work package 1 includes a rapid review and workshops, aiming to explore the effects of price increases in food and non-alcoholic beverages to facilitate the specification of food taxes and research design. METHODS: In this mixed-methods study, we first did a rapid review to examine relevant published evidence. A preplanned framework ensured a systematic approach, in which we searched PubMed, HMIC, Scopus, Google, Mintel/Mintel Food and Drink, and Business Source Ultimate for papers published in English from Jan 1, 2010, to Nov 2, 2022. This review was followed by three online workshops (in March, 2023), which used interactive padlets to explore food systems, food taxation policy, tax rationales, and a rapid review infographic. 14 stakeholders from non-governmental organisations (n=10), academia (n=2), the Civil Service (n=1), and a local authority (n=1) took part (gender or ethnicity were not recorded). A stakeholder recruitment grid was developed to ensure representation across public sectors and disciplines of public health, nutrition, environment, and economics. FINDINGS: The rapid review identified six tax options with a broadly positive impact on consumption and health (high fat, high sugar, high salt, "junk food", sugar-sweetened-beverages, and meats plus sugar-sweetened beverages). It generated five core rationales for a food tax: change consumption, reduce or prevent harm, change product affordability, raise revenue, and industry impact. Using the workshop feedback, health inequalities, economics, ease of implementation and animal welfare were additional key areas for a so-called real-world application of tax. Stakeholders questioned the taxes in the current economic and political climate. INTERPRETATION: The work highlights the need to develop an impactful food tax option that encompasses the five core rationales identified in the findings. The workshops identified key areas to explore further to understand the feasibility, impact, and logistics of implementing future food taxes. Being unable to deliver workshops in person due to difficulties of participants travelling to London was a limitation. However, switching online allowed for varied and well attended workshops. FUNDING: National Institute of Health Research (Ref: NIHR133927).

Which workplace health initiatives work, for whom, in what contexts, and how? A rapid realist review.

BACKGROUND: The work environment is an important determinant of health and health inequalities. Workplaces have a key role in preventing ill health. The WHO and Office for Health Improvement and Disparities encourage implementing employer-led workplace health award schemes tailored to specific contexts. Therefore, when designing and developing workplace initiatives it becomes imperative to know what works, for whom, and in what circumstances. This research aims to facilitate understanding of the various contexts and mechanisms through which workplace health initiatives are implemented while considering how these might affect employee health outcomes. METHODS: We did a rapid realist review to explore the different contexts (C) in which workplace initiatives are implemented that may fire a mechanism (M), leading to a change in employee health-related and business outcomes (O). We searched 12 databases for peer-reviewed papers published from June 1, 2019, to March 31, 2022 that referred to a workplace health and or wellbeing programme or intervention. There were no restrictions placed on study design. We recorded the impact of context and mechanisms on any health and business-related outcomes. The review was carried out in accordance with RAMESES publication standards. FINDINGS: 26 articles were included. Most studies were conducted in North America (n=13) and Europe (n=9), with four conducted in Australia and Oceania and one in Asia. We developed eight realist CMO programme theories. For example, when leaders are committed to employee health and wellbeing (C) (identified in 16 studies), demonstrated by role modelling healthy behaviours and actively promoting workers to engage in initiatives, employees feel valued and "permitted" to engage in healthy and wellbeing initiatives (M) which might lead to greater participation in health promotion activities (O). This review is registered with PROSPERO, CRD42022303262. INTERPRETATION: Findings contribute towards raising employers' awareness of what interventions might work for their employees. For instance, those interventions that encompass engagement of leadership at all levels to promote health and wellbeing are likely to leave employees feeling valued, motivated, and permitted to engage in interventions. Limitations of this study include potential biases arising from using rapid review processes and the inability to produce standardised recommendations. However, knowledge gained, which considers complexity and flexibility, might help inform, tailor, and support the implementation of future workplace health initiatives. FUNDING: National Institute for Health and Care Research (NIHR).

Opportunities to improve population health: possibilities for healthier food environments.

The recent Covid-19 pandemic highlighted stark social inequalities, notably around access to food, nutrition and to green or blue space (i.e. outdoor spaces with vegetation and water). Consequently, obesity is socio-economically patterned by this inequality; and while the environmental drivers of obesity are widely acknowledged, there is currently little upstream intervention. We know that living with obesity contributes to increasing health inequalities, and places healthcare systems under huge strain. Our environment could broadly be described obesogenic, in the sense of supporting unhealthful eating patterns and sedentary behaviour. Evidence points to the existence of nearly 700 UK obesity policies, all of which have had little success. Obesity prevention and treatment has focused on educational and behavioural interventions targeted at individual consumers. A more sustainable approach would be to try and change the environments that promote less healthy eating and high energy intake as well as sedentary behaviour. Approaches which modify the environment have the potential to assist in the prevention of this complex condition. This review paper focuses on the role of wider food environments or foodscapes. While there is an imperfect evidence base relating to the role of the foodscape in terms of the obesity crisis, policy, practice, civic society and industry must work together and take action now, in areas where current evidence suggests change is required. Despite the current cost-of-living crisis, shaping the foodscape to better support healthful eating decisions has the potential to be a key aspect of a successful obesity prevention intervention.

A mixed-method systematic review and meta-analysis of the influences of food environments and food insecurity on obesity in high-income countries.

Obesity remains a serious public health concern in rich countries and the current obesogenic food environments and food insecurity are predictors of this disease. The impact of these variables on rising obesity trends is, however, mixed and inconsistent, due to measurement issues and cross-sectional study designs. To further the work in this area, this review aimed to summarize quantitative and qualitative data on the relationship between these variables, among adults and children across high-income countries. A mixed-method systematic review was conducted using 13 electronic databases, up to August 2021. Two authors independently extracted data and evaluated quality of publications. Random-effects meta-analysis was used to estimate the odds ratio (OR) for the association between food insecurity and obesity. Where statistical pooling for extracted statistics related to food environments was not possible due to heterogeneity, a narrative synthesis was performed. Meta-analysis of 36,113 adults and children showed statistically significant associations between food insecurity and obesity (OR: 1.503, 95% confidence interval: 1.432-1.577, p < .05). Narrative synthesis showed association between different types of food environments and obesity. Findings from qualitative studies regarding a reliance on energy-dense, nutrient-poor foods owing to their affordability and accessibility aligned with findings from quantitative studies. Results from both qualitative and quantitative studies regarding the potential links between increased body weight and participation in food assistance programs such as food banks were supportive of weight gain. To address obesity among individuals experiencing food insecurity, wide-reaching approaches are required, especially among those surrounded by unhealthy food environments which could potentially influence food choice.

[Diagnostic and prognostic utility of cardiac magnetic resonance imaging in myocarditis]. / Apports diagnostique et pronostique de l'imagerie par résonance magnétique cardiaque dans la myocardite.

Cardiac magnetic resonance imaging (CMR) became over the last 30 years an essential tool in the management of patients with myocarditis. Noninvasive diagnosis of acute myocarditis relies on a clinical picture compatible with myocarditis and fulfilling of the updated 2018 Lake Louise criteria. These criteria include highlights of myocardial edema by conventional T2-weighted sequences or by T2 mapping in one hand and evidence of myocardial injury using late gadolinium enhancement sequences, T1 mapping or extra-cellular volume measurement in the other hand. It is recommended to perform basal examination in the 2 or 3 weeks following acute episode and to repeat CMR during follow-up. The literature reports excellent diagnostic accuracy, between 80% and 90%, making CMR a robust and reliable noninvasive alternative to endomyocardial biopsy. Besides, beyond its diagnostic performance, CMR can also help to identify patients with unfavourable long-term outcome. For instance, medio-ventricular and septal location of late gadolinium enhancement, degree of late gadolinium enhancement extent or high T2 mapping values are independent predictive factors of major cardio-vascular events.

Progression of Age-Related Macular Degeneration Among Individuals Homozygous for Risk Alleles on Chromosome 1 (CFH-CFHR5) or Chromosome 10 (ARMS2/HTRA1) or Both.

IMPORTANCE: Age-related macular degeneration (AMD) is a common cause of irreversible vision loss among individuals older than 50 years. Although considerable advances have been made in our understanding of AMD genetics, the differential effects of major associated loci on disease manifestation and progression may not be well characterized. OBJECTIVE: To elucidate the specific associations of the 2 most common genetic risk loci for AMD, the CFH-CFHR5 locus on chromosome 1q32 (Chr1) and the ARMS2/HTRA1 locus on chromosome 10q26 (Chr10)-independent of one another and in combination-with time to conversion to late-stage disease and to visual acuity loss. DESIGN, SETTING, AND PARTICIPANTS: This case series study included 502 individuals who were homozygous for risk variants at both Chr1 and Chr10 (termed Chr1&10-risk) or at either Chr1 (Chr1-risk) or Chr10 (Chr10-risk) and who had enrolled in Genetic and Molecular Studies of Eye Diseases at the Sharon Eccles Steele Center for Translational Medicine between September 2009 and March 2020. Multimodal imaging data were reviewed for AMD staging, including grading of incomplete and complete retinal pigment epithelium and outer retinal atrophy. MAIN OUTCOMES AND MEASURES: Hazard ratios and survival times for conversion to any late-stage AMD, atrophic or neovascular, and associated vision loss of 2 or more lines. RESULTS: In total, 317 participants in the Chr1-risk group (median [IQR] age at first visit, 75.6 [69.5-81.7] years; 193 women [60.9%]), 93 participants in the Chr10-risk group (median [IQR] age at first visit, 77.5 [72.2-84.2] years; 62 women [66.7%]), and 92 participants in the Chr1&10-risk group (median [IQR] age at first visit, 71.7 [68.0-76.3] years; 62 women [67.4%]) were included in the analyses. After adjusting for age and AMD grade at first visit, compared with 257 participants in the Chr1-risk group, 56 participants in the Chr1&10-risk group (factor of 3.3 [95% CI, 1.6-6.8]; P < .001) and 58 participants in the Chr10-risk group (factor of 2.6 [95% CI, 1.3-5.2]; P = .007) were more likely to convert to a late-stage phenotype during follow-up. This difference was mostly associated with conversion to macular neovascularization, which occurred earlier in participants with Chr1&10-risk and Chr10-risk. Eyes in the Chr1&10-risk group (median [IQR] survival, 5.7 [2.1-11.1] years) were 2.1 (95% CI, 1.1-3.9; P = .03) times as likely and eyes in the Chr10-risk group (median [IQR] survival, 6.3 [2.7-11.3] years) were 1.8 (95% CI, 1.0-3.1; P = .05) times as likely to experience a visual acuity loss of 2 or more lines compared with eyes of the Chr1-risk group (median [IQR] survival, 9.4 [4.1-* (asterisk indicates event rate did not reach 75%)] years). CONCLUSIONS AND RELEVANCE: These findings suggest differential associations of the 2 major AMD-related risk loci with structural and functional disease progression and suggest distinct underlying biological mechanisms associated with these 2 loci. These genotype-phenotype associations may warrant consideration when designing and interpreting AMD research studies and clinical trials.

Correction to: Human Pluripotent Stem Cells for High-Throughput Drug Screening and Characterization of Small Molecules.

This chapter was inadvertently published with an error, the ninth point under 'Materials' section must read.

An analysis of food and beverage advertising on bus shelters in a deprived area of Northern England.

OBJECTIVE: To quantify the extent of food and beverage advertising on bus shelters in a deprived area of the UK, to identify the healthfulness of advertised products, and any differences by level of deprivation. The study also sought to assess the creative strategies used and extent of appeal to young people. DESIGN: Images of bus shelter advertisements were collected via in person photography (in 2019) and Google Street View (photos recorded in 2018). Food and beverage advertisements were grouped into one of seventeen food categories and classified as healthy/less healthy using the UK Nutrient Profile Model. The deprivation level of the advertisement location was identified using the UK Index of Multiple Deprivation. SETTING: Middlesbrough and Redcar and Cleveland in South Teesside. PARTICIPANTS: N/A. RESULTS: Eight hundred and thirty-two advertisements were identified, almost half (48·9 %) of which were for foods or beverages. Of food and non-alcoholic beverage adverts, 35·1 % were less healthy. Most food advertisements (98·9 %) used at least one of the persuasive creative strategies. Food advertisements were found to be of appeal to children under 18 years of age (71·9 %). No differences in healthiness of advertised foods were found by level of deprivation. CONCLUSIONS: Food advertising is extensive on bus shelters in parts of the UK, and a substantial proportion of this advertising is classified as less healthy and would not be permitted to be advertised around television programming for children. Bus shelter advertising should be considered part of the UK policy deliberations around restricting less healthy food marketing exposure.

Human Pluripotent Stem Cells for High-Throughput Drug Screening and Characterization of Small Molecules.

Human pluripotent stem cells (hPSCs), such as induced pluripotent stem cells (iPSCs), hold great promise for drug discovery, toxicology studies, and regenerative medicine. Here, we describe standardized protocols and experimental procedures that combine automated cell culture for scalable production of hPSCs with quantitative high-throughput screening (qHTS) in miniaturized 384-well plates. As a proof of principle, we established dose-response assessments and determined optimal concentrations of 12 small molecule compounds that are commonly used in the stem cell field. Multi-parametric analysis of readouts from diverse assays including cell viability, mitochondrial membrane potential, plasma membrane integrity, and ATP production was used to distinguish normal biological responses from cellular stress induced by small molecule treatment. Collectively, the establishment of integrated workflows for cell manufacturing, qHTS, high-content imaging, and data analysis provides an end-to-end platform for industrial-scale projects and should leverage the drug discovery process using hPSC-derived cell types.

The effectiveness of e-health interventions for the treatment of overweight or obesity in children and adolescents: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to examine the effectiveness of e-health interventions for the treatment of children and adolescents with overweight or obesity. Databases were searched up to November 2020. Studies were randomized controlled trials where interventions were delivered via e-health (e.g., computers, tablets, and smartphones, but not phone calls). Studies should target the treatment of overweight or obesity in children or their agent of changes and report body mass index (BMI) or BMI z-score. A meta-analysis using a random-effects model was conducted. Nineteen studies met the inclusion criteria, and 60% were of high quality. The narrative review revealed variation in behavior change strategies and modes of delivery. The pooled mean reduction in BMI or BMI z-score showed evidence for a nonzero effect (standardized mean difference = -0.31, 95% confidence interval -0.49 to -0.13), with moderately high heterogeneity between studies (I2 = 74%, p < 0.001). Subgroup analysis revealed high heterogeneity in studies with a high or unclear risk of bias. E-health interventions can be effective in treating children and adolescents with overweight and obesity and should be considered by practitioners and policymakers. However, an understanding of the most effective and acceptable intervention components, long-term benefits, and sustainability should be further studied.

Robotic high-throughput biomanufacturing and functional differentiation of human pluripotent stem cells.

Efficient translation of human induced pluripotent stem cells (hiPSCs) requires scalable cell manufacturing strategies for optimal self-renewal and functional differentiation. Traditional manual cell culture is variable and labor intensive, posing challenges for high-throughput applications. Here, we established a robotic platform and automated all essential steps of hiPSC culture and differentiation under chemically defined conditions. This approach allowed rapid and standardized manufacturing of billions of hiPSCs that can be produced in parallel from up to 90 different patient- and disease-specific cell lines. Moreover, we established automated multi-lineage differentiation and generated functional neurons, cardiomyocytes, and hepatocytes. To validate our approach, we compared robotic and manual cell culture operations and performed comprehensive molecular and cellular characterizations (e.g., single-cell transcriptomics, mass cytometry, metabolism, electrophysiology) to benchmark industrial-scale cell culture operations toward building an integrated platform for efficient cell manufacturing for disease modeling, drug screening, and cell therapy.

'Pizza every day - why?': A survey to evaluate the impact of COVID-19 guidelines on secondary school food provision in the UK.

The nutritional requirements of adolescence and the reported poor UK eating behaviours of young people are a significant public health concern. Schools are recognised as an effective 'place' setting to enable improvement to nutrition outcomes. The COVID-19 pandemic resulted in UK school closures from March 2020. In re-opening in September 2020, schools were required to meet guidelines to ensure the minimised impact of COVID-19 on the population (DfE 2020). We aimed to evaluate the impact of COVID-19 school guidelines on secondary and post-16 (16-18 years) food provision. An online survey was posted on 8th October to 1st December 2020, targeted at young people, parents and staff of secondary/post-16 education establishments in the UK. Two hundred and fifty-two responses were received, of which 91% reported a change in their school food provision, 77% reported time for lunch was shortened and 44% indicated the provision was perceived as less healthy during September 2020 (post-lockdown school return) compared with March 2020 (pre-lockdown). Analyses demonstrated that time, limited choice and healthiness impacted negatively upon young people's school food experience. The COVID-19 pandemic has presented a huge challenge to the delivery of healthy school food to young people. Therefore, schools require more support in following national food standards and incorporating nutrition education and behaviour change strategies within current guidelines.

A versatile polypharmacology platform promotes cytoprotection and viability of human pluripotent and differentiated cells.

Human pluripotent stem cells (hPSCs) are capable of extensive self-renewal yet remain highly sensitive to environmental perturbations in vitro, posing challenges to their therapeutic use. There is an urgent need to advance strategies that ensure safe and robust long-term growth and functional differentiation of these cells. Here, we deployed high-throughput screening strategies to identify a small-molecule cocktail that improves viability of hPSCs and their differentiated progeny. The combination of chroman 1, emricasan, polyamines, and trans-ISRIB (CEPT) enhanced cell survival of genetically stable hPSCs by simultaneously blocking several stress mechanisms that otherwise compromise cell structure and function. CEPT provided strong improvements for several key applications in stem-cell research, including routine cell passaging, cryopreservation of pluripotent and differentiated cells, embryoid body (EB) and organoid formation, single-cell cloning, and genome editing. Thus, CEPT represents a unique poly-pharmacological strategy for comprehensive cytoprotection, providing a rationale for efficient and safe utilization of hPSCs.

Whole genome sequencing identifies novel genetic mutations in patients with eczema herpeticum.

BACKGROUND: Eczema herpeticum (EH) is a rare complication of atopic dermatitis (AD) caused by disseminated herpes simplex virus (HSV) infection. The role of rare and/or deleterious genetic variants in disease etiology is largely unknown. This study aimed to identify genes that harbor damaging genetic variants associated with HSV infection in AD with a history of recurrent eczema herpeticum (ADEH+). METHODS: Whole genome sequencing (WGS) was performed on 49 recurrent ADEH+ (≥3 EH episodes), 491 AD without a history of eczema herpeticum (ADEH-) and 237 non-atopic control (NA) subjects. Variants were annotated, and a gene-based approach (SKAT-O) was used to identify genes harboring damaging genetic variants associated with ADEH+. Genes identified through WGS were studied for effects on HSV responses and keratinocyte differentiation. RESULTS: Eight genes were identified in the comparison of recurrent ADEH+to ADEH-and NA subjects: SIDT2, CLEC7A, GSTZ1, TPSG1, SP110, RBBP8NL, TRIM15, and FRMD3. Silencing SIDT2 and RBBP8NL in normal human primary keratinocytes (NHPKs) led to significantly increased HSV-1 replication. SIDT2-silenced NHPKs had decreased gene expression of IFNk and IL1b in response to HSV-1 infection. RBBP8NL-silenced NHPKs had decreased gene expression of IFNk, but increased IL1b. Additionally, silencing SIDT2 and RBBP8NL also inhibited gene expression of keratinocyte differentiation markers keratin 10 (KRT10) and loricrin (LOR). CONCLUSION: SIDT2 and RBBP8NL participate in keratinocyte's response to HSV-1 infection. SIDT2 and RBBP8NL also regulate expression of keratinocyte differentiation genes of KRT10 and LOR.

The impact of, and views on, school food intervention and policy in young people aged 11-18 years in Europe: A mixed methods systematic review.

Understanding the social and environmental influencers of eating behaviours has the potential to improve health outcomes for young people. This review aims to explore the effectiveness of school nutrition interventions and the perceptions of young people experiencing a nutrition focused intervention or change in school food policy. A comprehensive systematic search identified studies published between 1 December 2007 to 20 February 2020. Twenty-seven studies were included: 22 quantitative studies of nutrition related outcomes and five qualitative studies reporting views and perceptions of young people (combined sample of 22,138 participants, mean ages 12-18 years). The primary outcome was nutrition knowledge/dietary behaviours, with secondary outcomes exploring body mass index (BMI) and wellbeing. Due to the heterogeneity of studies, a narrative results description is presented. The findings demonstrate that school nutrition programmes can be effective in reducing sugar, sugar sweetened beverages (SSB) and saturated fat and increasing fruit and vegetable (FV) intake. The lived experiences of young people in a school context provide valuable insights that should be considered in the development of effective school food policy and interventions. This review affirms the significant role that schools can play in supporting good nutrition in all young people and provides opportunities to inform the school food agenda.

Frailty Does Not Impact Caregiver Burden in Patients with Cirrhosis.

BACKGROUND: Frailty is common and is associated with increased mortality, lower quality of life, and higher readmission rates in cirrhotic patients. Not only are these outcomes important, but further understanding the impact of frailty on a caregiver's life is crucial to better comprehend caregiver burden in cirrhotic patients and develop strategies to improve care for patients and their caregivers. METHODS: A single-center, prospective study was conducted of cirrhotic patients and their caregivers between 4/1/2019 and 11/1/2019. Frailty testing combined aspects from the Fried Frailty Instrument, Short Physical Performance Battery, and activities of daily living. Caregivers completed questionnaires to evaluate caregiver burden using the Zarit Burden Interview (ZBI-12), and perceived social support, using the Interpersonal Support Evaluation List. RESULTS: In total, 94 cirrhotic patients were included, 50% males with a median age of 63.1 years. The most common etiology of cirrhosis was nonalcoholic steatohepatitis. Frailty was prevalent (45.1%). In total, 12.8% of caregivers reported a high burden based on ZBI-12. There was no association between frailty and caregiver burden, hospitalization rates, or death. However, frailty was associated with a higher number of outpatient GI visits (p = 0.002). Lower perceived social support among caregivers was associated with a higher caregiver burden (p < 0.0001). CONCLUSION: Frailty is prevalent in cirrhotic patients but is not associated with higher rates of caregiver burden. Low perceived social support among caregivers, however, was associated with higher caregiver burden. It is important to recognize the impact of caregiver burden on caregivers of cirrhotic patients and ensure caregivers have the appropriate support to mitigate burden.

Robotic High-Throughput Biomanufacturing and Functional Differentiation of Human Pluripotent Stem Cells.

Efficient translation of human induced pluripotent stem cells (hiPSCs) depends on implementing scalable cell manufacturing strategies that ensure optimal self-renewal and functional differentiation. Currently, manual culture of hiPSCs is highly variable and labor-intensive posing significant challenges for high-throughput applications. Here, we established a robotic platform and automated all essential steps of hiPSC culture and differentiation under chemically defined conditions. This streamlined approach allowed rapid and standardized manufacturing of billions of hiPSCs that can be produced in parallel from up to 90 different patient-and disease-specific cell lines. Moreover, we established automated multi-lineage differentiation to generate primary embryonic germ layers and more mature phenotypes such as neurons, cardiomyocytes, and hepatocytes. To validate our approach, we carefully compared robotic and manual cell culture and performed molecular and functional cell characterizations (e.g. bulk culture and single-cell transcriptomics, mass cytometry, metabolism, electrophysiology, Zika virus experiments) in order to benchmark industrial-scale cell culture operations towards building an integrated platform for efficient cell manufacturing for disease modeling, drug screening, and cell therapy. Combining stem cell-based models and non-stop robotic cell culture may become a powerful strategy to increase scientific rigor and productivity, which are particularly important during public health emergencies (e.g. opioid crisis, COVID-19 pandemic).

Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program.

Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models.