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The demand for fish protein continues to increase and currently accounts for 17% of total animal protein consumption by humans. About 90% of marine fish stocks are fished at or above maximum sustainable levels, with aquaculture propagating as one of the fastest growing food sectors to address some of this demand. Cell-cultivated seafood production is an alternative approach to produce nutritionally-complete seafood products to meet the growing demand. This cellular aquaculture approach offers a sustainable, climate resilient and ethical biotechnological approach as an alternative to conventional fishing and fish farming. Additional benefits include reduced antibiotic use and the absence of mercury. Cell-cultivated seafood also provides options for the fortification of fish meat with healthier compositions, such as omega-3 fatty acids and other beneficial nutrients through scaffold, media or cell approaches. This review addresses the biomaterials, production processes, tissue engineering approaches, processing, quality, safety, regulatory, and social aspects of cell-cultivated seafood, encompassing where we are today, as well as the road ahead. The goal is to provide a roadmap for the science and technology required to bring cellular aquaculture forward as a mainstream food source.

Given the expanding global population and finite resources, it is imperative to explore alternative technologies for food production. These technologies play a crucial role in ensuring the provision of safe, nutritious, and sustainable food options to meet the growing demand. Cellular agriculture plays an important in developing an alternative method for developing food products. While, cellular agriculture is emerging rapidly, food safety aspects and regulatory frameworks stayed behind. Despite developing several regulatory framework papers on cellular agriculture, there is no systematic approach for developing a comprehensive food safety plan (FSP), particularly for cultivated seafood. Thus, the overall goal of this article is to develop a FSP for cultivated seafood. The main differences between the food safety plan for cultivated seafood and the conventional seafood industries were the number of allergens in cultivated seafood products, including soy, wheat, and fish cells, compared to only fish for the conventional seafood industry. In addition, there are several hazards associated with mycoplasma in cultivated seafood, which should be considered. This guidance intends to help regulatory agencies, food safety experts, startup companies, and the cultivated seafood industry by providing a valuable platform to develop regulations, guidance, and food safety plans applicable to most cultivated seafood companies. This article will also help the industry to identify the hazards in their processing line and develop preventive controls, and as a comprehensive food safety plan, it could be easily adapted for other cultivated seafood products. This guidance applied systematic approaches to developing food safety plans using cell culture, pharmaceuticals, fermentation, seafood, meat, and aquaponics safety plans, collaborating with experts with different backgrounds, and working closely with the conventional and cultivated meat and seafood industries.

BACKGROUND: Fibrosis-4 (FIB4) is a recommended noninvasive test to assess hepatic fibrosis among patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we used FIB4 trajectory over time (ie, slope of FIB4) as a surrogate marker of liver fibrosis progression and examined if FIB4 slope is associated with clinical and genetic factors among individuals with clinically defined MASLD within the Million Veteran Program Cohort. METHODS: In this retrospective cohort study, FIB4 slopes were estimated through linear regression for participants with clinically defined MASLD and FIB4

We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism. One of these, PNPLA3 p.Ile148Met, interacts with alcohol intake, obesity and diabetes on the risk of cirrhosis and hepatocellular carcinoma (HCC). We develop a polygenic risk score that associates with the progression from cirrhosis to HCC. By focusing on prioritized genes from common variant analyses, we find that rare coding variants in GPAM associate with lower ALT, supporting GPAM as a potential target for therapeutic inhibition. In conclusion, this study provides insights into the genetic underpinnings of cirrhosis.

BackgroundPerson-centered care is critical for delivering high-quality diabetes care. Shared decision making (SDM) is central to person-centered care, and in diabetes care, it can improve decision quality, patient knowledge, and patient risk perception. Delivery of person-centered care can be facilitated with the use of patient decision aids (PtDAs). We developed MyDiabetesPlan, an interactive SDM and goal-setting PtDA designed to help individualize care priorities and support an interprofessional approach to SDM. ObjectiveThis study aims to assess the impact of MyDiabetesPlan on decisional conflict, diabetes distress, health-related quality of life, and patient assessment of chronic illness care at the individual patient level. MethodsA two-step, parallel, 10-site cluster randomized controlled trial (first step: provider-directed implementation only; second step: both provider- and patient-directed implementation 6 months later) was conducted. Participants were adults 18 years and older with diabetes and 2 other comorbidities at 10 family health teams (FHTs) in Southwestern Ontario. FHTs were randomly assigned to MyDiabetesPlan (n=5) or control (n=5) through a computer-generated algorithm. MyDiabetesPlan was integrated into intervention practices, and clinicians (first step) followed by patients (second step) were trained on its use. Control participants received static generic Diabetes Canada resources. Patients were not blinded. Participants completed validated questionnaires at baseline, 6 months, and 12 months. The primary outcome at the individual patient level was decisional conflict; secondary outcomes were diabetes distress, health-related quality of life, chronic illness care, and clinician intention to practice interprofessional SDM. Multilevel hierarchical regression models were used. ResultsAt the end of the study, the intervention group (5 clusters, n=111) had a modest reduction in total decisional conflicts compared with the control group (5 clusters, n=102; −3.5, 95% CI −7.4 to 0.42). Although there was no difference in diabetes distress or health-related quality of life, there was an increase in patient assessment of chronic illness care (0.7, 95% CI 0.4 to 1.0). ConclusionsUse of goal-setting decision aids modestly improved decision quality and chronic illness care but not quality of life. Our findings may be due to a gap between goal setting and attainment, suggesting a role for optimizing patient engagement and behavioral support. The next steps include clarifying the mechanisms by which decision aids impact outcomes and revising MyDiabetesPlan and its delivery. Trial RegistrationClinicalTrials.gov NCT02379078; https://clinicaltrials.gov/ct2/show/NCT02379078

BACKGROUND & AIMS: There is growing acceptance that principles of palliative care should be integrated into the management of serious illnesses affecting the liver, such as acute-on-chronic liver failure (ACLF). However, rates, patterns, and predictors of specialty palliative care consultation among patients with ACLF have not been well-described. METHODS: We performed a retrospective cohort study of patients hospitalized with ACLF between 1/1/2008 and 12/31/2018 using the VOCAL cohort. Patients were followed until 6/2021. We used mixed-effects regression analyses to identify significant patient and facility factors associated with palliative care consultation. We examined timing of consultation, the influence of ACLF characteristics, and facility-level variation on receipt of palliative care consultation. RESULTS: We identified 21,987 patients hospitalized with ACLF, of whom 30.5% received specialty palliative care consultation. Higher ACLF grade (ACLF-2 [odds ratio (OR) 1.82, 95% CI 1.67-1.99], ACLF-3 [OR 3.06, 95% CI 2.76-3.40]), prior specialty palliative care consultation (OR 2.62, 95% CI 2.36-2.91), and hepatocellular carcinoma (OR 2.10, 95% CI 1.89-2.33) were associated with consultation. Consultation occurred latest and closest to the time of death for patients with ACLF-3 compared to ACLF-1 and ACLF-2. Significant facility-level variation in consultation persisted among patients with ACLF-3, despite adjusting for multiple patient and facility factors. CONCLUSION: In this large cohort of hospitalized patients with ACLF, specialty palliative care consultation was rare, more common in patients with higher grade ACLF, and tended to occur closer to the time of death for the sickest patients. Greater attention should be placed on earlier integration of palliative care during acute hospitalizations in patients with ACLF. IMPACT AND IMPLICATIONS: Though palliative care consultation is recommended for patients with acute-on-chronic liver failure, there is no data demonstrating how often this occurs during hospitalizations, on a population level. We found that consultation occurs in only 30.5% of patients and occurs later for patients with grade 3 acute-on-chronic liver failure. Our data should provoke clinicians to urgently consider quality improvement efforts to integrate palliative care into the management of these seriously ill patients.

Traumatic Brain injury-induced disturbances in mitochondrial fission-and-fusion dynamics have been linked to the onset and propagation of neuroinflammation and neurodegeneration. However, cell-type-specific contributions and crosstalk between neurons, microglia, and astrocytes in mitochondria-driven neurodegeneration after brain injury remain undefined. We developed a human three-dimensional in vitro triculture tissue model of a contusion injury composed of neurons, microglia, and astrocytes and examined the contributions of mitochondrial dysregulation to neuroinflammation and progression of injury-induced neurodegeneration. Pharmacological studies presented here suggest that fragmented mitochondria released by microglia are a key contributor to secondary neuronal damage progression after contusion injury, a pathway that requires astrocyte-microglia crosstalk. Controlling mitochondrial dysfunction thus offers an exciting option for developing therapies for TBI patients.

We present a search for extragalactic fast blue optical transients (FBOTs) during Phase I of the Zwicky Transient Facility (ZTF). We identify 38 candidates with durations above half-maximum light 1 day < t 1/2 < 12 days, of which 28 have blue (g − r ≲ −0.2 mag) colors at peak light. Of the 38 transients (28 FBOTs), 19 (13) can be spectroscopically classified as core-collapse supernovae (SNe): 11 (8) H- or He-rich (Type II/IIb/Ib) SNe, 6 (4) interacting (Type IIn/Ibn) SNe, and 2 (1) H&He-poor (Type Ic/Ic-BL) SNe. Two FBOTs (published previously) had predominantly featureless spectra and luminous radio emission: AT2018lug (The Koala) and AT2020xnd (The Camel). Seven (five) did not have a definitive classification: AT 2020bdh showed tentative broad Hα in emission, and AT 2020bot showed unidentified broad features and was 10 kpc offset from the center of an early-type galaxy. Ten (eight) have no spectroscopic observations or redshift measurements. We present multiwavelength (radio, millimeter, and/or X-ray) observations for five FBOTs (three Type Ibn, one Type IIn/Ibn, one Type IIb). Additionally, we search radio-survey (VLA and ASKAP) data to set limits on the presence of radio emission for 24 of the transients. All X-ray and radio observations resulted in nondetections; we rule out AT2018cow-like X-ray and radio behavior for five FBOTs and more luminous emission (such as that seen in the Camel) for four additional FBOTs. We conclude that exotic transients similar to AT2018cow, the Koala, and the Camel represent a rare subset of FBOTs and use ZTF’s SN classification experiments to measure the rate to be at most 0.1% of the local core-collapse SN rate.

Quantum mechanics requires the time evolution of the wave function to be linear. While this feature has been associated with the preservation of causality, a consistent causal nonlinear theory was recently developed. Interestingly, this theory is unavoidably sensitive to the full physical spread of the wave function, rendering existing experimental tests for nonlinearities inapplicable. Here, using well-controlled motional superpositions of a trapped ion, we set a stringent limit of 5.4×10^{-12} on the magnitude of the unitless scaling factor ε[over ˜]_{γ} for the predicted causal nonlinear perturbation.

PURPOSE We offered a practice facilitation intervention to family physicians in Ontario, Canada, known to have large numbers of patients not yet vaccinated against coronavirus disease 2019 (COVID-19). METHODS We conducted a multimethod process evaluation embedded within a randomized controlled trial (clinical trial #NCT05099497). We collected descriptive statistics regarding engagement and qualitative interview data from family physicians and practice facilitators, as well as data from facilitator field notes. We analyzed and triangulated the data using thematic analysis and mapped barriers to and enablers for implementation to structural, organizational, physician, and patient factors. RESULTS Of the 300 approached, 90 family physicians (30%) accepted facilitation. Of these, 57% received technical support to identify unvaccinated patients, 29% used trained medical student volunteers to contact patients on their behalf, and 30% used automated calling to reach patients. Key factors affecting engagement with the intervention were staff shortages owing to COVID-19 (structural), clinic characteristics such as technical issues and gatekeeping by staff, which prevented facilitators from talking with physicians (organizational), burnout (physician), and specialized populations that required targeted resources (patient). The facilitator's ability to address technical issues and connect family physicians with medical students helped with engagement. CONCLUSIONS Strategies to help underresourced family physicians serving high- needs populations for issues of public health importance, such as vaccine promotion, must acknowledge the scarcity of physicians' time and provide new resources. To successfully engage family physicians, practice facilitators should seek to build trust and relationships over time, including with front-office staff. Key words: practice facilitation; vaccines; COVID-19; process evaluation, INTRODUCTION Many Canadians consider family physicians to be their most trusted source of vaccine information, (1,2) underscoring the important role family doctors play in encouraging vaccine uptake, addressing hesitancies, and [...]

Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,187 controls. Seventy-seven loci exceeded genome-wide significance, including 25 without prior NAFLD or alanine aminotransferase associations, with one additional locus identified in European American-only and two in African American-only analyses (P

The purpose of this paper is to extend and evaluate methods of "Bayesian historical borrowing" applied to longitudinal data with a focus on parameter recovery and predictive performance. Bayesian historical borrowing allows researchers to utilize information from previous data sources and to adjust the extent of borrowing based on the similarity of current data to historical data. We examine the utility of three "static" historical borrowing methods including complete pooling, Bayesian synthesis with aggregated data-dependent priors, traditional power priors, and two "dynamic" borrowing methods including Bayesian dynamic borrowing and commensurate priors. Using data from two administrations of the United States Early Childhood Longitudinal Study, we evaluate these methods in terms of in-sample simulation statistics, as well as pseudo out-of-sample measures of predictive performance. A case study examining growth in reading competency over time revealed that for one historical cycle, most methods of historical borrowing perform similarly with respect to predictive performance and parameter recovery. Pooling and power priors performed relatively poorly across the conditions in this study, particularly when the current data and the historical data were heterogeneous. Results from a comprehensive simulation study revealed that the advantages of different historical borrowing methods vary across different evaluation criteria. Overall, Bayesian dynamic borrowing and commensurate priors are no worse, and in some cases better, than other methods in terms of parameter recovery and predictive performance, and considering a previous paper by Kaplan et al. (Psychometrika, 10.1007/s11336-022-09869-3, 2022) found clear benefits of Bayesian dynamic borrowing over other methods of historical borrowing in the multilevel context using data from the Program for International Student Assessment (PISA) with five historical cycles, this paper argues that Bayesian dynamic borrowing or commensurate priors is a prudent choice for borrowing information from previous cycles of longitudinal data.

The purpose of this paper is to extend and evaluate methods of "Bayesian historical borrowing" applied to longitudinal data with a focus on parameter recovery and predictive performance. Bayesian historical borrowing allows researchers to utilize information from previous data sources and to adjust the extent of borrowing based on the similarity of current data to historical data. We examine the utility of three "static" historical borrowing methods including complete pooling, Bayesian synthesis with aggregated data-dependent priors, traditional power priors, and two "dynamic" borrowing methods including Bayesian dynamic borrowing and commensurate priors. Using data from two administrations of the United States Early Childhood Longitudinal Study, we evaluate these methods in terms of in-sample simulation statistics, as well as pseudo out-of-sample measures of predictive performance. A case study examining growth in reading competency over time revealed that for one historical cycle, most methods of historical borrowing perform similarly with respect to predictive performance and parameter recovery. Pooling and power priors performed relatively poorly across the conditions in this study, particularly when the current data and the historical data were heterogeneous. Results from a comprehensive simulation study revealed that the advantages of different historical borrowing methods vary across different evaluation criteria. Overall, Bayesian dynamic borrowing and commensurate priors are no worse, and in some cases better, than other methods in terms of parameter recovery and predictive performance, and considering a previous paper by Kaplan et al. (Psychometrika, 10.1007/s11336-022-09869-3, 2022) found clear benefits of Bayesian dynamic borrowing over other methods of historical borrowing in the multilevel context using data from the Program for International Student Assessment (PISA) with five historical cycles, this paper argues that Bayesian dynamic borrowing or commensurate priors is a prudent choice for borrowing information from previous cycles of longitudinal data. [The article was published in "Large-scale Assessments in Education" (EJ1362749).]

Bayesian latent change score modeling (LCSM) was used to compare models of triannual (fall, winter, spring) change on elementary math computation and concepts/applications curriculum-based measures. Data were collected from elementary students in Grades 2-5, approximately 700 to 850 students in each grade (47%-54% female; 78%-79% White, 10%-11% Black, 2%-4% Hispanic/Latino, 2%-4% Asian, 2-4% Native American or Pacific Islander; 13%-14% English learner; 10%-14% had special education individualized education plans). Results converged with common nonlinear growth patterns from the assessment norms and prior independent findings. However, Bayesian LCSMs captured practically relevant sources of change not observed in prior studies. Practical and methodological implications for screening and data-based decision-making in multitiered systems of support, limitations, and future directions are discussed.