Reconstructing axial progenitor field dynamics in mouse stem cell-derived embryoids.

Embryogenesis requires substantial coordination to translate genetic programs to the collective behavior of differentiating cells, but understanding how cellular decisions control tissue morphology remains conceptually and technically challenging. Here, we combine continuous Cas9-based molecular recording with a mouse embryonic stem cell-based model of the embryonic trunk to build single-cell phylogenies that describe the behavior of transient, multipotent neuro-mesodermal progenitors (NMPs) as they commit into neural and somitic cell types. We find that NMPs show subtle transcriptional signatures related to their recent differentiation and contribute to downstream lineages through a surprisingly broad distribution of individual fate outcomes. Although decision-making can be heavily influenced by environmental cues to induce morphological phenotypes, axial progenitors intrinsically mature over developmental time to favor the neural lineage. Using these data, we present an experimental and analytical framework for exploring the non-homeostatic dynamics of transient progenitor populations as they shape complex tissues during critical developmental windows.

Motivation and emotional distraction interact and affect executive functions.

Previous research on cool-hot executive function (EF) interactions has examined the effects of motivation and emotional distraction on cool EF separately, focusing on one EF component at a time. Although both incentives and emotional distractors have been shown to modulate attention, how they interact and affect cool EF processes is still unclear. Here, we used an experimental paradigm that manipulated updating, inhibition, and shifting demands to determine the interactions of motivation and emotional distraction in the context of cool EF. Forty-five young adults (16 males, 29 females) completed the go/no-go (inhibition), two-back (updating), and task-switching (shifting) tasks. Monetary incentives were implemented to manipulate motivation, and task-irrelevant threatening or neutral faces were presented before the target stimulus to manipulate emotional distraction. We found that incentives significantly improved no-go accuracy, two-back accuracy, and reaction time (RT) switch cost. While emotional distractors had no significant effects on overall task performance, they abolished the incentive effects on no-go accuracy and RT switch cost. Altogether, these findings suggest that motivation and emotional distraction interact in the context of cool EF. Specifically, transient emotional distraction disrupts the upregulation of control activated by incentives. The present investigation has advanced knowledge about the relationship between cool and hot EF and highlights the importance of considering motivation-emotion interactions for a fuller understanding of control.

Improving prime editing with an endogenous small RNA-binding protein.

Prime editing enables the precise modification of genomes through reverse transcription of template sequences appended to the 3' ends of CRISPR-Cas guide RNAs1. To identify cellular determinants of prime editing, we developed scalable prime editing reporters and performed genome-scale CRISPR-interference screens. From these screens, a single factor emerged as the strongest mediator of prime editing: the small RNA-binding exonuclease protection factor La. Further investigation revealed that La promotes prime editing across approaches (PE2, PE3, PE4 and PE5), edit types (substitutions, insertions and deletions), endogenous loci and cell types but has no consistent effect on genome-editing approaches that rely on standard, unextended guide RNAs. Previous work has shown that La binds polyuridine tracts at the 3' ends of RNA polymerase III transcripts2. We found that La functionally interacts with the 3' ends of polyuridylated prime editing guide RNAs (pegRNAs). Guided by these results, we developed a prime editor protein (PE7) fused to the RNA-binding, N-terminal domain of La. This editor improved prime editing with expressed pegRNAs and engineered pegRNAs (epegRNAs), as well as with synthetic pegRNAs optimized for La binding. Together, our results provide key insights into how prime editing components interact with the cellular environment and suggest general strategies for stabilizing exogenous small RNAs therein.

Startle: A star homoplasy approach for CRISPR-Cas9 lineage tracing.

CRISPR-Cas9-based genome editing combined with single-cell sequencing enables the tracing of the history of cell divisions, or cellular lineage, in tissues and whole organisms. Although standard phylogenetic approaches may be applied to reconstruct cellular lineage trees from this data, the unique features of the CRISPR-Cas9 editing process motivate the development of specialized models that describe the evolution of CRISPR-Cas9-induced mutations. Here, we introduce the "star homoplasy" evolutionary model that constrains a phylogenetic character to mutate at most once along a lineage, capturing the "non-modifiability" property of CRISPR-Cas9 mutations. We derive a combinatorial characterization of star homoplasy phylogenies and use this characterization to develop an algorithm, "Startle", that computes a maximum parsimony star homoplasy phylogeny. We demonstrate that Startle infers more accurate phylogenies on simulated lineage tracing data compared with existing methods and finds parsimonious phylogenies with fewer metastatic migrations on lineage tracing data from mouse metastatic lung adenocarcinoma.

Capturing Emerging Experiential Knowledge for Vaccination Guidelines Through Natural Language Processing: Proof-of-Concept Study.

BACKGROUND: Experience-based knowledge and value considerations of health professionals, citizens, and patients are essential to formulate public health and clinical guidelines that are relevant and applicable to medical practice. Conventional methods for incorporating such knowledge into guideline development often involve a limited number of representatives and are considered to be time-consuming. Including experiential knowledge can be crucial during rapid guidance production in response to a pandemic but it is difficult to accomplish. OBJECTIVE: This proof-of-concept study explored the potential of artificial intelligence (AI)-based methods to capture experiential knowledge and value considerations from existing data channels to make these insights available for public health guideline development. METHODS: We developed and examined AI-based methods in relation to the COVID-19 vaccination guideline development in the Netherlands. We analyzed Dutch messages shared between December 2020 and June 2021 on social media and on 2 databases from the Dutch National Institute for Public Health and the Environment (RIVM), where experiences and questions regarding COVID-19 vaccination are reported. First, natural language processing (NLP) filtering techniques and an initial supervised machine learning model were developed to identify this type of knowledge in a large data set. Subsequently, structural topic modeling was performed to discern thematic patterns related to experiences with COVID-19 vaccination. RESULTS: NLP methods proved to be able to identify and analyze experience-based knowledge and value considerations in large data sets. They provide insights into a variety of experiential knowledge that is difficult to obtain otherwise for rapid guideline development. Some topics addressed by citizens, patients, and professionals can serve as direct feedback to recommendations in the guideline. For example, a topic pointed out that although travel was not considered as a reason warranting prioritization for vaccination in the national vaccination campaign, there was a considerable need for vaccines for indispensable travel, such as cross-border informal caregiving, work or study, or accessing specialized care abroad. Another example is the ambiguity regarding the definition of medical risk groups prioritized for vaccination, with many citizens not meeting the formal priority criteria while being equally at risk. Such experiential knowledge may help the early identification of problems with the guideline's application and point to frequently occurring exceptions that might initiate a revision of the guideline text. CONCLUSIONS: This proof-of-concept study presents NLP methods as viable tools to access and use experience-based knowledge and value considerations, possibly contributing to robust, equitable, and applicable guidelines. They offer a way for guideline developers to gain insights into health professionals, citizens, and patients' experience-based knowledge, especially when conventional methods are difficult to implement. AI-based methods can thus broaden the evidence and knowledge base available for rapid guideline development and may therefore be considered as an important addition to the toolbox of pandemic preparedness.

Pharmacy Deserts and Pharmacies' Roles Post-Extreme Weather and Climate Events in the United States: A Scoping Review.

BACKGROUND: The effects of climate change are seen with a rise of extreme weather and climate events (EWCEs) which lead to the closures of many healthcare facilities, such as community pharmacies. Pharmacists in community pharmacies are seen as the most accessible healthcare professional to the public and are responsible for the continued delivery of care to patients. However, amid closures due to EWCEs and the emergence of pharmacy deserts, there is decreased access to pharmacies and a disruption of care. OBJECTIVE: It is important to address the preparedness and accessibility of pharmacies post-EWCEs to guide future research and policy. Additionally, to tackle health disparities that arise due to pharmacy deserts, the populations most affected by a decreased access to pharmacies should be identified. We conducted a scoping review to assess the preparedness and accessibility of pharmacies post-EWCEs and to identify populations most affected by pharmacy deserts. METHODS: We searched PubMed, Embase, and Web of Science from January 1, 2012 to September 30, 2022 and included all English-language, peer-reviewed primary literature that examined the preparedness and accessibility of community pharmacies in the United States post-EWCEs and addressed disparities within pharmacy deserts. Studies meeting these criteria were screened of their titles and abstracts by the first author and discrepancies were resolved with co-authors. We used Covidence for data extraction. RESULTS: A total of 472 studies were identified (196 duplicates removed) and after screening, 53 studies were assessed for eligibility. The results of included publications (N = 26) showed that pharmacists and pharmacies are not equipped with the necessary emergency protocols which could lead to decreased access of pharmacies in the wake of EWCEs. Pharmacy deserts disproportionately affect residents living in rural, lower income, and Black/African American and Hispanic/Latino neighborhoods. The lack of preparedness of pharmacies post-EWCEs could worsen medication access. CONCLUSION: This scoping review addresses challenges impacting pharmacies and patients post-EWCEs and within pharmacy deserts. In times of increased need, these challenges implicate the well-being of communities affected by EWCEs by breaking the continuum of care and access to medications. Here we offer suggestions for future research and directions for policy change.

Recording morphogen signals reveals origins of gastruloid symmetry breaking.

When cultured in three dimensional spheroids, mammalian stem cells can reproducibly self-organize a single anterior-posterior axis and sequentially differentiate into structures resembling the primitive streak and tailbud. Whereas the embryo's body axes are instructed by spatially patterned extra-embryonic cues, it is unknown how these stem cell gastruloids break symmetry to reproducibly define a single anterior-posterior (A-P) axis. Here, we use synthetic gene circuits to trace how early intracellular signals predict cells' future anterior-posterior position in the gastruloid. We show that Wnt signaling evolves from a homogeneous state to a polarized state, and identify a critical 6-hour time period when single-cell Wnt activity predicts future cellular position, prior to the appearance of polarized signaling patterns or morphology. Single-cell RNA sequencing and live-imaging reveal that early Wnt-high and Wnt-low cells contribute to distinct cell types and suggest that axial symmetry breaking is driven by sorting rearrangements involving differential cell adhesion. We further extend our approach to other canonical embryonic signaling pathways, revealing that even earlier heterogeneity in TGFß signaling predicts A-P position and modulates Wnt signaling during the critical time period. Our study reveals a sequence of dynamic cellular processes that transform a uniform cell aggregate into a polarized structure and demonstrates that a morphological axis can emerge out of signaling heterogeneity and cell movements even in the absence of exogenous patterning cues.

Population-size history inferences from the coho salmon (Oncorhynchus kisutch) genome.

Coho salmon (Oncorhynchus kisutch) are a culturally and economically important species that return from multiyear ocean migrations to spawn in rivers that flow to the Northern Pacific Ocean. Southern stocks of coho salmon in Canada and the United States have significantly declined over the past quarter century, and unfortunately, conservation efforts have not reversed this trend. To assist in stock management and conservation efforts, we generated a chromosome-level genome assembly. We also resequenced the genomes of 83 coho salmon across the North American range to identify nucleotide variants and understand the demographic histories of these salmon by modeling effective population size from genome-wide data. From demographic history modeling, we observed reductions in effective population sizes between 3,750 and 8,000 years ago for several northern sampling sites, which may correspond to bottleneck events during recolonization after glacial retreat.

PPARγ (Peroxisome Proliferator-Activated Receptor γ) Deacetylation Suppresses Aging-Associated Atherosclerosis and Hypercholesterolemia.

BACKGROUND: Atherosclerosis is a medical urgency manifesting at the onset of hypercholesterolemia and is associated with aging. Activation of PPARγ (peroxisome proliferator-activated receptor γ) counteracts metabolic dysfunction influenced by aging, and its deacetylation displays an atheroprotective property. Despite the marked increase of PPARγ acetylation during aging, it is unknown whether PPARγ acetylation is a pathogenic contributor to aging-associated atherosclerosis. METHODS: Mice with constitutive deacetylation-mimetic PPARγ mutations on lysine residues K268 and K293 (2KR) in an LDL (low-density lipoprotein)-receptor knockout (Ldlr-/-) background (2KR:Ldlr-/-) were aged for 18 months on a standard laboratory diet to examine the cardiometabolic phenotype, which was confirmed in Western-type diet-fed 2KR:Ldlr+/- mice. Whole-liver RNA-sequencing and in vitro studies in bone marrow-derived macrophages were conducted to decipher the mechanism. RESULTS: In contrast to severe atherosclerosis in WT:Ldlr-/- mice, aged 2KR:Ldlr-/- mice developed little to no plaque, which was underlain by a significantly improved plasma lipid profile, with particular reductions in circulating LDL. The protection from hypercholesterolemia was recapitulated in Western-type diet-fed 2KR:Ldlr+/- mice. Liver RNA-sequencing analysis revealed suppression of liver inflammation rather than changes in cholesterol metabolism. This anti-inflammatory effect of 2KR was attributed to polarized M2 activation of macrophages. Additionally, the upregulation of core circadian component Bmal1 (brain and muscle ARNT-like 1), perceived to be involved in anti-inflammatory immunity, was observed in the liver and bone marrow-derived macrophages. CONCLUSIONS: PPARγ deacetylation in mice prevents the development of aging-associated atherosclerosis and hypercholesterolemia, in association with the anti-inflammatory phenotype of 2KR macrophages.

Generation and age of immigration on later life cognitive performance in KHANDLE.

OBJECTIVES: We examined the association of generational status and age at immigration with later life cognitive outcomes in a diverse sample of Latinos and Asian Americans. DESIGN: Baseline data were obtained from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, and a prospective cohort is initiated in 2017. SETTING: Older adults in Northern California. PARTICIPANTS: Our cohort consisted of Asians (n = 411) and Latinos (n = 340) who were on average 76 years old (SD = 6.8). MEASUREMENTS: We used multivariable linear regression models to estimate associations between generational status and age at immigration (collapsed into one five-level variable) with measures of verbal episodic memory, semantic memory, and executive function, adjusting for age, gender, race and ethnicity, and own- and parental education. RESULTS: Generational status and age at immigration were associated with cognitive outcomes in a graded manner. Compared to third-generation or higher immigrants, first-generation immigration in adulthood was associated with lower semantic memory (ß = -0.96; 95% CI: -1.12, -0.81) than immigration in adolescence (ß = -0.68; 95% CI: -0.96, -0.41) or childhood (ß = -0.28; 95% CI: -0.49, -0.06). Moreover, immigration in adulthood was associated with lower executive function (ß = -0.63; 95% CI: -0.78, -0.48) than immigration in adolescence (ß = -0.49; 95% CI: -0.75, -0.23). Similarly, compared to third-generation individuals, first-generation immigrants had lower executive functioning scores. CONCLUSIONS: Our study supports the notion that sociocontextual influences in early life impact later life cognitive scores. Longitudinal studies are needed to further clarify how immigration characteristics affect cognitive decline.

APOE Effects on Late Life Cognitive Trajectories in Diverse Racial/Ethnic Groups.

OBJECTIVE: This study evaluated: (1) apolipoprotein E (APOE) ϵ4 prevalence among Black, Latino, and White older adults, (2) associations of APOE ϵ4 status with baseline level and change over time of cognitive outcomes across groups, and (3) combined impact of APOE ϵ4 prevalence and magnitude of effect on cognitive decline within each racial/ethnic group. METHOD: Participants included 297 White, 138 Latino, and 149 Black individuals from the longitudinal UC Davis Diversity Cohort who had APOE genotyping and ≥2 cognitive assessments. Magnitude of associations of ϵ4 with cognitive baseline and change across racial/ethnic groups was tested with multilevel parallel process longitudinal analyses and multiple group models. RESULTS: ϵ4 prevalence in Black (46%) and White participants (46%) was almost double that of Latino participants (24%). ϵ4 was associated with poorer baseline episodic memory only in White participants (p = .001), but had a moderately strong association with episodic memory change across all racial/ethnic groups (Blacks= -.061 SD/year, Latinos = -.055,Whites= -.055). ϵ4 association with semantic memory change was strongest in White participants (-.071), intermediate in Latino participants (-.041), and weakest in Black participants (-.022). CONCLUSION: Calculated cognitive trajectories across racial/ethnic groups were influenced in an additive manner by ϵ4 prevalence and strength of association with cognitive decline within the group. Group differences in ϵ4 prevalences and associations of ϵ4 with cognition may suggest different pathways from APOE to cognitive decline, and, AD possibly having less salient impact on cognitive decline in non-White participants. Differential effects of APOE on episodic memory and non-memory cognition have important implications for understanding how APOE influences late life cognitive decline.

A randomized control trial of a behavioral intervention for older adults with subjective cognitive complaints that combines cognitive rehabilitation strategies and lifestyle modifications.

This study examined the effectiveness of a 10-week cognitive rehabilitation and lifestyle modifying intervention that integrated compensation strategies, engagement in brain activities, and improving everyday function. The trial was registered with ClinicalTrials.gov (NCT03549078). Older adults with subjective cognitive concerns and normal performance on a cognitive screener were randomized into the intervention (n = 28) or waitlist control (n = 29) groups. The total sample comprised 57 individuals (age, mean = 74.8, SD = 6.5), mostly female (80.4% of the total sample), and well educated (education years: mean = 15.9, SD = 2.1). Outcome measures were completed at baseline, and immediately and 3- and 6-months post-intervention. Intervention participants reported significant improvements in aspects of everyday functioning and select compensation strategies and brain health activities. Increased compensation strategy use was maintained at 6-month follow up. This intervention has benefits for improving everyday functioning and increasing engagement with compensation strategies and brain health activities.

The mechanics of implementation strategies and measures: advancing the study of implementation mechanisms.

BACKGROUND: There is a fundamental gap in understanding the causal mechanisms by which strategies for implementing evidence-based practices address local barriers to effective, appropriate service delivery. Until this gap is addressed, scientific knowledge and practical guidance about which implementation strategies to use in which contexts will remain elusive. This research project aims to identify plausible strategy-mechanism linkages, develop causal models for mechanism evaluation, produce measures needed to evaluate such linkages, and make these models, methods, and measures available in a user-friendly website. The specific aims are as follows: (1) build a database of strategy-mechanism linkages and associated causal pathway diagrams, (2) develop psychometrically strong, pragmatic measures of mechanisms, and (3) develop and disseminate a website of implementation mechanisms knowledge for use by diverse stakeholders. METHODS: For the first aim, a combination of qualitative inquiry, expert panel methods, and causal pathway diagramming will be used to identify and confirm plausible strategy-mechanism linkages and articulate moderators, preconditions, and proximal and distal outcomes associated with those linkages. For the second aim, rapid-cycle measure development and testing methods will be employed to create reliable, valid, pragmatic measures of six mechanisms of common strategies for which no high-quality measures exist. For the third aim, we will develop a user-friendly website and searchable database that incorporates user-centered design, disseminating the final product using social marketing principles. DISCUSSION: Once strategy-mechanism linkages are identified using this multi-method approach, implementation scientists can use the searchable database to develop tailored implementation strategies and generate more robust evidence about which strategies work best in which contexts. Moreover, practitioners will be better able to select implementation strategies to address their specific implementation problems. New horizons in implementation strategy development, optimization, evaluation, and deployment are expected to be more attainable as a result of this research, which will lead to enhanced implementation of evidence-based interventions for cancer control, and ultimately improvements in patient outcomes.

Lobar versus sublobar resection in clinical stage IA primary lung cancer with occult N2 disease.

OBJECTIVES: Sublobar resection is increasingly being utilized for early-stage lung cancers, but optimal management when final pathology shows unsuspected mediastinal nodal disease is unclear. This study tested the hypothesis that lobectomy has improved survival compared to sublobar resection for clinical stage IA tumours with occult N2 disease. METHODS: The use of sublobar resection and lobectomy for patients in the National Cancer Database who underwent primary surgical resection for clinical stage IA non-small-cell lung cancer with pathologic N2 disease between 2010 and 2017 was evaluated using logistic regression. Survival was assessed with Kaplan-Meier analysis, log-rank test and Cox proportional hazards model. RESULTS: A total of 2419 patients comprised the study cohort, including 320 sublobar resections (13.2%) and 2099 lobectomies (86.8%). Older age, female sex, smaller tumour size and treatment at an academic facility predicted the use of sublobar resection. Patients undergoing lobectomy had larger tumours (2.40 vs 2.05 cm, P < 0.001) and more lymph nodes examined (11 vs 5, P < 0.001). Adjuvant chemotherapy use was similar between the 2 groups (sublobar 79.4% vs lobectomy 77.4%, P = 0.434). Sublobar resection was not associated with worse survival compared to lobectomy in both univariate (5-year survival 46.6% vs 45.2%, P = 0.319) and multivariable Cox proportional hazards analysis (hazard ratio 0.97, P = 0.789). CONCLUSIONS: Clinical stage IA non-small-cell lung cancer patients with N2 disease on final pathology have similar long-term survival with either sublobar resection or lobectomy. Patients with occult N2 disease after sublobar resection may not require reoperation for completion lobectomy but should instead proceed to adjuvant chemotherapy.

A multifaceted signal recorder of cellular experiences using Cas12a base-editing.

Technological advances have led to the emergence of lineage tracers, but signal recorders for mammalian systems have remained elusive. Kempton et al. have developed a Cas12a base-editing signal recorder capable of capturing diverse signals and operating in various experimental designs. The recorder enables new opportunities to chronicle cellular history.

Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution.

Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth and expansion to neighboring and distal tissues. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma and tracked tumor evolution from single-transformed cells to metastatic tumors at unprecedented resolution. We found that the loss of the initial, stable alveolar-type2-like state was accompanied by a transient increase in plasticity. This was followed by the adoption of distinct transcriptional programs that enable rapid expansion and, ultimately, clonal sweep of stable subclones capable of metastasizing. Finally, tumors develop through stereotypical evolutionary trajectories, and perturbing additional tumor suppressors accelerates progression by creating novel trajectories. Our study elucidates the hierarchical nature of tumor evolution and, more broadly, enables in-depth studies of tumor progression.

Evaluating the quality, safety, and functionality of commonly used smartphone apps for bipolar disorder mood and sleep self-management.

BACKGROUND: Individuals with bipolar disorder (BD) are increasingly turning to smartphone applications (apps) for health information and self-management support. While reviews have raised concerns regarding the effectiveness and safety of publicly available apps for BD, apps surveyed may not reflect what individuals with BD are using. The present study had two aims: first, to characterize the use of health apps to support mood and sleep amongst people with BD, and second, to evaluate the quality, safety and functionality of the most commonly used self-management apps. METHODS: A web-based survey was conducted to explore which apps people with BD reported using to support self-management of mood and sleep. The characteristics of the most commonly nominated apps were described using a standardized framework, including their privacy policy, clinical foundations, and functionality. RESULTS: Respondents (n = 919) were 77.9% female with a mean age of 36.9 years. 41.6% of participants (n = 382) reported using a self-management app to support mood or sleep. 110 unique apps were nominated in relation to mood, and 104 unique apps nominated in relation to sleep; however, most apps were only mentioned once. The nine most frequently nominated apps related to mood and sleep were subject to further evaluation. All reviewed apps offered a privacy policy, however user control over data was limited and the complexity of privacy policies was high. Only one app was developed for BD populations. Half of reviewed apps had published peer-reviewed evidence to support their claims of efficacy, but little research was specific to BD. CONCLUSION: Findings illustrate the potential of smartphone apps to increase the reach of psychosocial interventions amongst people with BD. Apps were largely created by commercial developers and designed for the general population, highlighting a gap in the development and dissemination of evidence-informed apps for BD. There may be risks in using generic health apps for BD self-management; clinicians should enquire about patients' app use to foster conversations about their particular benefits and limitations.

Risk stratification and assessment framework for international travel and border measures amidst the COVID-19 pandemic - A Malaysian perspective.

BACKGROUND: Guided by the best practices adapted from national and international bodies including the World Health Organization (WHO), the Centers for Disease Control (CDC), and the UK Joint Biosecurity Centre (JBC), this paper aims to develop and provide an empirical risk stratification and assessment framework for advancing the safe resumption of global travel during the COVID-19 pandemic. METHOD: Variables included in our model are categorized into four pillars: (i) incidence of cases, (ii) reliability of case data, (iii) vaccination, and (iv) variant surveillance. These measures are combined based on weights that reflect their corresponding importance in risk assessment within the context of the pandemic to calculate the risk score for each country. As a validation step, the outcome of the risk stratification from our model is compared against four countries. RESULTS: Our model is found to have good agreement with these benchmarked risk designations for 27 out of the top 30 countries with the strongest travel ties to Malaysia (90%). Each factor within this model signifies its importance and can be adapted by governing bodies to address the changing needs of border control policies for the recommencement of international travel. CONCLUSION: In practice, the proposed model provides a turnkey solution for nations to manage transmission risk by enabling stakeholders to make informed, evidence-based decisions to minimize fluctuations of imported cases and serves as a structure to support the improvement, planning, and activation of public health control measures.