Extensive Process Research Articles

Somatic genome architecture and molecular evolution are decoupled in "young" linage-specific gene families in ciliates.

The evolution of lineage-specific gene families remains poorly studied across the eukaryotic tree of life, with most analyses focusing on the recent evolution of de novo genes in model species. Here we explore the origins of lineage-specific genes in ciliates, a ~1 billion year old clade of microeukaryotes that are defined by their division of somatic and germline functions into distinct nuclei. Previous analyses on conserved gene families have shown the effect of ciliates' unusual genome architecture on gene family evolution: extensive genome processing-the generation of thousands of gene-sized somatic chromosomes from canonical germline chromosomes-is associated with larger and more diverse gene families. To further study the relationship between ciliate genome architecture and gene family evolution, we analyzed lineage specific gene families from a set of 46 transcriptomes and 12 genomes representing x species from eight ciliate classes. We assess how the evolution lineage-specific gene families occurs among four groups of ciliates: extensive fragmenters with gene-size somatic chromosomes, non-extensive fragmenters with "large'' multi-gene somatic chromosomes, Heterotrichea with highly polyploid somatic genomes and Karyorelictea with 'paradiploid' somatic genomes. Our analyses demonstrate that: 1) most lineage-specific gene families are found at shallow taxonomic scales; 2) extensive genome processing (i.e., gene unscrambling) during development likely influences the size and number of young lineage-specific gene families; and 3) the influence of somatic genome architecture on molecular evolution is increasingly apparent in older gene families. Altogether, these data highlight the influences of genome architecture on the evolution of lineage-specific gene families in eukaryotes.

Endogenously Gated DNA Walking Machine for Prescreened MicroRNA Detection in Extracellular Vesicles.

Tumor-derived extracellular vesicle (T-EV) microRNAs have been investigated as promising biomarkers in clinical diagnosis as well as disease progression monitoring. However, the expression profiles of microRNA in different tissues vary widely, the precise monitoring of microRNA levels in EVs originating from diseased tissues is susceptible to background interference, thus remains a challenge. Conventional assays require extensive processing, such as EV isolation and even sample lysis, which is both slow and laborious, and the cumbersome pretreatment could spoil the downstream analysis. To address this issue, we developed a generalizable strategy for T-EVs-selective activation and therefore specific amplified microRNA imaging. The conditional signal amplification is established by integrating a traditional DNA walker system with endogenously activated motif to achieve sensitized microRNA imaging in T-EVs. The preorganized endogenous activation with additional sensing criteria narrowed the scope against the complex specimens, and the amplified sensing with reduced off-target signals was supposed to be sensitive to monitor the tiny changes of microRNA expression during the disease course, which holds great potential for accurate diagnosis and prognosis.

Controlling aggregation of diketopyrrolopyrroles in water

Charge repulsion can be used to control and fine tune the supramolecular aggregation of amino acid substituted diketopyrrolopyrroles in water. This is a simple method to access a number of different aggregation states with distinct photophysical properties without the need for extensive synthetic tuning, process engineering, or solvent optimisation. Most importantly, these different aggregates show different optical gaps, HOMO-LUMO gaps, electroactivity, and exciton binding energies. These systems expand the absorbance range achieved from one chromophore unit and also create systems with large Stokes shifts. This work therefore answers the demand for tailoring aggregate structures by manipulating charge repulsion in an aqueous environment.

Standardized Iterative Genome Editing Method for Escherichia coli Based on CRISPR-Cas9.

The introduction of complex biosynthetic pathways into the hosts' chromosomes is gaining attention with the development of synthetic biology. While CRISPR-Cas9 has been widely employed for gene knock-in, the process of multigene insertion remains cumbersome due to laborious and empirical gene cloning procedures. To address this, we devised a standardized iterative genome editing system for Escherichia coli, harnessing the power of CRISPR-Cas9 and MetClo assembly. This comprehensive toolkit comprises two fundamental elements based on the Golden Gate standard for modular assembly of sgRNA or CRISPR arrays and donor DNAs. We achieved a gene insertion efficiency of up to 100%, targeting a single locus. Expression of tracrRNA using a strong promoter enhances multiplex genomic insertion efficiency to 7.3%, compared with 0.76% when a native promoter is used. To demonstrate the robust capabilities of this genome editing toolbox, we successfully integrated 5-10 genes from the coenzyme B12 biosynthetic pathway ranging from 5.3 to 8 Kb in length into the chromosome of E. coli chassis cells, resulting in 14 antibiotic-free, plasmid-free producers. Following an extensive screening process involving genes from diverse sources, cistronic design modifications, and chromosome repositioning, we obtained a recombinant strain yielding 1.49 mg L-1 coenzyme B12, the highest known titer achieved by using E. coli as the producer. Illuminating its user-friendliness, this genome editing system is an exceedingly versatile tool for expediently integrating complex biosynthetic pathway genes into hosts' genomes, thus facilitating pathway optimization for chemical production.

The importance of hazard-consistency when estimating seismic residual drifts in steel moment frames

Residual drifts are routinely used to assess the post-earthquake safety of buildings. Despite their importance, studies on the probabilistic assessment of residual drifts in multi-storey buildings with Steel Moment Resisting Frames (SMRF) are far less common than those dealing with their transient peak drift counterpart. More seriously, although residual drift prediction models have been developed with a particular broad ground-motion type or soil condition in mind, all models proposed to date remain oblivious to the central issue of hazard consistency. Hence, missing the causal connection between the seismic hazard level and the ground-motion suite used and potentially compromising the meaningfulness of their results. This oversight is expected to introduce a bias in the estimation of residual drifts but its magnitude has not yet been properly evaluated. In this paper, we evaluate and quantify the significance of these effects. To this end, we use the Conditional Scenario Spectra framework, which provides a set of realistic earthquake spectra with assigned rates of occurrences based on their spectral shape and intensity, thus preserving the critical relationship of hazard consistency. Nonlinear Response History Analyses (NRHA) of 24 deteriorating SMRFs under 816 ground-motion records are performed to construct a database of residual drift demands. These NRHA results are used to examine the residual drift trends and to construct benchmark residual drift hazard curves. An extensive feature selection process employing several Machine Learning (ML) algorithms precedes the development of hybrid data-driven predictive models. Finally, we compare our hazard-consistent predictions with currently available models and quantify the massive under- and over-estimations associated with previously proposed non-hazard-consistent assumptions.

A Containerized Service-Based Integration Framework for Heterogeneous-Geospatial-Analysis Models

The integration of geospatial-analysis models is crucial for simulating complex geographic processes and phenomena. However, compared to non-geospatial models and traditional geospatial models, geospatial-analysis models face more challenges owing to extensive geographic data processing and complex computations involved. One core issue is how to eliminate model heterogeneity to facilitate model combination and capability integration. In this study, we propose a containerized service-based integration framework named GeoCSIF, specifically designed for heterogeneous-geospatial-analysis models. Firstly, by designing the model-servicized structure, we shield the heterogeneity of model structures so that different types of geospatial-analysis models can be effectively described and integrated based on standardized constraints. Then, to tackle the heterogeneity in model dependencies, we devise a prioritization-based orchestration method, facilitating optimized combinations of large-scale geospatial-analysis models. Lastly, considering the heterogeneity in execution modes, we design a heuristic scheduling method that establishes optimal mappings between models and underlying computational resources, enhancing both model stability and service performance. To validate the effectiveness and progressiveness of GeoCSIF, a prototype system was developed, and its integration process for flood disaster models was compared with mainstream methods. Experimental results indicate that GeoCSIF possesses superior performance in model management and service efficiency.

Influence of co-deposition modification on mode I and II interlaminar toughness of epoxy laminates interleaved with waste textiles using experimental measurement and finite element technique

Interlaminar delamination has been a persistent problem that restricts the ability of fiber reinforced laminated composites under applied load. The influence of polyethyleneimine-catechol (PEI-CCh) co-deposition modification on the mode I (GIC) and II interlaminar fracture toughness (GIIC) of plain glass fiber fabric reinforced epoxy composites (PGFRECs) were discussed using double cantilever beam (DCB) and end notch flexural (ENF) tests. It was found that interfacial properties of PET/epoxy and PET/cotton/epoxy interfaces were substantially improved after co-deposited modification, which laid a solid foundation for enhancing the resistance to interlaminar delamination. GIC and GIIC in platform of crack propagation greatly increased with the introduction of co-deposition layer. The fracture surfaces of delaminated failure specimens were observed by scanning electron microscope. The higher propagation fracture toughness for co-deposition modified PGFRECs is due to the anchoring effect of functional layer combining waste fabrics with epoxy matrix to provide favorable stress transfer channel prior to macroscopic crack formation. In regard to the delamination crack, new crack generation and bridge fiber failure mainly dominated the mode I crack extension process, while zigzag sections were particularly common for mode II fracture specimens.

High-dimensional Metaverse Platforms and the Virtually Extended Self.

The study of cognition has traditionally used low-dimensional measures and stimulus presentations that emphasize laboratory control over high-dimensional (i.e., ecologically valid) tools that reflect the activities and interactions in everyday living. Although controlled experimental presentations in laboratories have enhanced our understanding of cognition for both healthy and clinical cohorts, high dimensionality may extend reality and cognition. High-dimensional Metaverse approaches use extended reality (XR) platforms with dynamic stimulus presentations that couple humans and simulation technologies to extend cognition. The plan for this paper is as follows: The "Extending from low to high-dimensional studies of cognition" section discusses current needs for high-dimensional stimulus presentations that reflect everyday cognitive activities. In the "Algorithmic devices and digital extension of cognition" section, technologies of the extended mind are introduced with the Metaverse as a candidate cognitive process for extension. Next, in the "A neurocognitive framework for understanding technologies of the extended mind" section, a framework and model are proposed for understanding the neural correlates of human technology couplings in terms of automatic algorithmic processes (limbic-ventral striatal loop); reflective cognition (prefrontal-dorsal striatal loop); and algorithmic processing (insular cortex). The algorithmic processes of human-technology interactions can, over time, become an automated and algorithmic coupling of brain and technology. The manuscript ends with a brief summary and discussion of the ways in which the Metaverse can be used for studying how persons respond to high-dimensional stimuli in simulations that approximate real-world activities and interactions.

Communication Model in Agricultural Zakat Counseling in Nagari Sungai Tarab

Basically, extension is a communication activity. Zakat extension communication is a form of process of conveying information to the relevant community, systematically, planned and directed in order to change behavior and opinions of the relevant community. The communication process carried out by zakat counselors to the relevant communities is not solely due to the transfer of information from communicator to communicant but how the message conveyed by the communicator reaches the communicant properly. So that awareness arises from the communicants to try and apply the information they get. In accordance with the aim of counseling itself, namely to help the community to have knowledge about everything related to zakat and to provide a modern view and new paradigm about zakat which is a need for the community. The formulation of the problem in this research is What is the Communication Model used by the instructor? zakat in Nagari Sungai Tarab? Meanwhile, the aim of this research is to determine the mode of communism carried out by agricultural zakat instructors in Nagari Sungai Tarab. This research uses field research with qualitative descriptive methods. The data collection techniques that researchers used were field observations, interviews and documentation. The reason researchers use qualitative descriptive research is to obtain data and understand the phenomena experienced by informants. The results of this research state that there are two communication models that have been used by researchers in the agricultural zakat extension process in Nagari Sungai Tarab. Namely the Linear communication model and the Interactional communication model, each communication used is very influential in this research where these two communications function to convey information to the relevant community in a systematic, planned and directed manner for the sake of sustainably changing the behavior and opinions of the relevant community. The related community is muzaki. Meanwhile, the communication model in agricultural zakat counseling consists of an individual approach, a group approach and a mass approach

Chromosomal rearrangements played an important role in the speciation of rice rats of genus Cerradomys (Rodentia, Sigmodontinae, Oryzomyini)

Rodents of the genus Cerradomys belong to tribe Oryzomyini, one of the most diverse and speciose groups in Sigmodontinae (Rodentia, Cricetidae). The speciation process in Cerradomys is associated with chromosomal rearrangements and biogeographic dynamics in South America during the Pleistocene era. As the morphological, molecular and karyotypic aspects of Myomorpha rodents do not evolve at the same rate, we strategically employed karyotypic characters for the construction of chromosomal phylogeny to investigate whether phylogenetic relationships using chromosomal data corroborate the radiation of Cerradomys taxa recovered by molecular phylogeny. Comparative chromosome painting using Hylaeamys megacephalus (HME) whole chromosome probes in C. langguthi (CLA), Cerradomys scotii (CSC), C. subflavus (CSU) and C. vivoi (CVI) shows that karyotypic variability is due to 16 fusion events, 2 fission events, 10 pericentric inversions and 1 centromeric repositioning, plus amplification of constitutive heterochromatin in the short arms of the X chromosomes of CSC and CLA. The chromosomal phylogeny obtained by Maximum Parsimony analysis retrieved Cerradomys as a monophyletic group with 97% support (bootstrap), with CSC as the sister to the other species, followed by a ramification into two clades (69% of branch support), the first comprising CLA and the other branch including CVI and CSU. We integrated the chromosome painting analysis of Eumuroida rodents investigated by HME and Mus musculus (MMU) probes and identified several syntenic blocks shared among representatives of Cricetidae and Muridae. The Cerradomys genus underwent an extensive karyotypic evolutionary process, with multiple rearrangements that shaped extant karyotypes. The chromosomal phylogeny corroborates the phylogenetic relationships proposed by molecular analysis and indicates that karyotypic diversity is associated with species radiation. Three syntenic blocks were identified as part of the ancestral Eumuroida karyotype (AEK): MMU 7/19 (AEK 1), MMU 14 (AEK 10) and MMU 12 (AEK 11). Besides, MMU 5/10 (HME 18/2/24) and MMU 8/13 (HME 22/5/11) should be considered as signatures for Cricetidae, while MMU 5/9/14, 5/7/19, 5 and 8/17 for Sigmodontinae.

Prognostic and immunological role of adaptor related protein complex 3 subunit mu2 in colon cancer

The expression levels and prognostic role of AP3M2 in colorectal adenocarcinoma (CRAC) have yet to be fully unveiled. Our study comprehensively investigated the clinical significance of AP3M2 in colorectal cancer through an extensive bioinformatics data mining process (TCGA, GEO, GEPIA, Timer, Ualcan, ROCPLOT, and David), followed by experimental validation. We found AP3M2 is a cancer gene, which can be used to distinguish between colorectal cancer and colorectal adenomas, liver metastasis, lung metastasis, colorectal polyp. Higher AP3M2 expression levels were associated with longer overall survival in colon adenocarcinoma. AP3M2 might be the primary biomarker for oxaliplatin in colon cancer and an acquired resistance biomarker for oxaliplatin and 5-fu. AP3M2 was positively associated with CD274, CTLA4. AP3M2 might be associated with T-cell, NF-kappaB transcription factor activity, and response to hypoxia. AP3M2 could predict chemotherapy effectiveness and prognosis for colon cancer patients. AP3M2 might inhibit tumor growth via influencing tumor-infiltrating immune cells in the context of Tumor microenvironment. AP3M2 plays as an oncogene in CRAC and is suggested as a new potential biotarget for therapy.

Management of Intellectual Property as a Generator of Resources in Mexican Higher Education Institutions

This paper was developed to analyze the level of implementation of intellectual property management processes in Higher Education Institutions (HEI). Intellectual Property management processes in the public sector have been reduced, at least in understanding the concept, to the processes of protecting and maintaining intellectual property titles; however, it is a more extensive process than conceptualized. In this sense, Martinez et al. (2018) generated a methodology involving 19 indicators (processes) of intellectual property management implemented during the R&D&I process. These indicators were used to measure their implementation in Mexican public sector HEIs with information from the transparency portal. The research shows the importance of generating multidisciplinary groups in R&D&I processes, enhancing the financial redundancy of research investment.

Recurrence of Pulmonary Tuberculosis Associated with Comorbidities - Current Interdisciplinary Problem

Introduction. The recurrence of pulmonary tuberculosis remains a significant public health problem in many countries of the world, despite the remarkable progress in the treatment and rehabilitation of patients with new cases of tuberculosis. It is demonstrated that the high incidence of recurrence of pulmonary tuberculosis is conditioned by the influence of some factors combination. Currently, the comorbidities, which impose the risk of disease recurrence directly or indirectly, are of a major importance. Thus, it is important to study the clinical and epidemiological characteristics of pulmonary tuberculosis recurrence associated with the comorbidities. Materials and methods. There were studied 715 patients with pulmonary tuberculosis recurrence, including 503 patients with comorbidities, as well as statistical reporting data for the Right Bank region of the Dniester River and ATU (Autonomous Territorial Unit) of Gagauzia, Republic of Moldova during 2019-2021. Results. The obtained results demonstrate that in phthisiopulmonology the presence of comorbidities constitutes a significant and important medico-social problem. In the structure of relapses associated with comorbidities, it was noted the predominance of extensive infiltrative processes, high frequency of cases with destruction in the lung tissue and bacillary cases. The need to review and improve the general antituberculosis measures accepted both in the work of phthisiopneumologists and primary care specialists is argued in order to improve the prognosis of TB treatment associated with comorbidities. Conclusion. The recurrence of pulmonary tuberculosis associated with comorbidities requires an integrated multidisciplinary approach.

TFOS lifestyle report: Effects of environmental conditions on the ocular surface

This presentation summarizes the findings of the Environmental Conditions Subcommittee of the recent Workshop of the Tear Film & Ocular Surface Society, entitled “A Lifestyle Epidemic: Ocular Surface Disease” (www.tearfilm.org). The tear film and the ocular surface morphofunctional unit are directly exposed to the surrounding environment. Environmental factors with potential, probable or well‐established impact on the ocular surface health include: climate factors (temperature, humidity, windspeed, altitude, dew point, ultraviolet light), outdoor and indoor pollutants (gases, particulate matter, and airborne pollutants) and allergens. These factors interact each other in complex and concurrent ways, contributing to different specific ocular surface diseases, including dry eye, ocular allergies, conjunctival and corneal degenerative conditions, injuries, and neoplastic diseases. Age and sex, race/ethnicity, geographical area, and seasonality are some of the key elements playing a relevant role in environmental factors‐related ocular surface diseases.Throughout an extensive narrative review process, this report evaluated in detail the evidence about each of those environmental conditions and the associated ocular surface diseases. Distinct environmental conditions may increase risk and/or aggravate certain conditions and may contribute to specific diseases. Indeed, a systematic review, conducted to investigate the association between outdoor pollution and dry eye signs and symptoms, found evidence supporting the risk factor role of air pollution (from NO2 and CO, but not from PM10) and soil pollution (from chromium).

Meta learning addresses noisy and under-labeled data in machine learning-guided antibody engineering

Machine learning-guided protein engineering is rapidly progressing; however, collecting high-quality, large datasets remains a bottleneck. Directed evolution and protein engineering studies often require extensive experimental processes to eliminate noise and label protein sequence-function data. Meta learning has proven effective in other fields in learning from noisy data via bi-level optimization given the availability of a small dataset with trusted labels. Here, we leverage meta learning approaches to overcome noisy and under-labeled data and expedite workflows in antibody engineering. We generate yeast display antibody mutagenesis libraries and screen them for target antigen binding followed by deep sequencing. We then create representative learning tasks, including learning from noisy training data, positive and unlabeled learning, and learning out of distribution properties. We demonstrate that meta learning has the potential to reduce experimental screening time and improve the robustness of machine learning models by training with noisy and under-labeled training data.

Glycosort: A Computational Solution to Post-process Quantitative Large-Scale Intact Glycopeptide Analyses.

Protein glycosylation is a post-translational modification involving the addition of carbohydrates to proteins and plays a crucial role in protein folding and various biological processes such as cell recognition, differentiation, and immune response. The vast array of natural sugars available allows the generation of plenty of unique glycan structures in proteins, adding complexity to the regulation and biological functions of glycans. The diversity is further increased by enzymatic site preferences and stereochemical conjugation, leading to an immense amount of different glycan structures. Understanding glycosylation heterogeneity is vital for unraveling the impact of glycans on different biological functions. Evaluating site occupancies and structural heterogeneity aids in comprehending glycan-related alterations in biological processes. Several software tools are available for large-scale glycoproteomics studies; however, integrating identification and quantitative data to assess heterogeneity complexity often requires extensive manual data processing. To address this challenge, we present a python script that automates the integration of Byonic and MaxQuant outputs for glycoproteomic data analysis. The script enables the calculation of site occupancy percentages by glycans and facilitates the comparison of glycan structures and site occupancies between two groups. This automated tool offers researchers a means to organize and interpret their high-throughput quantitative glycoproteomic data effectively.

The Future of Trade and Environment: A Roadmap for Reconciling Two Competing Goals

The global market has experienced an unprecedented increase in cross-border trading, culminating in substantial economic growth for numerous nations. However, this extensive process of economic integration has cast a shadow on various associated domains. Trading activities, intricately linked to the environment due to their reliance on natural resources for production, have indisputably left their mark on global environmental conditions. International trade and environmental preservation, as distinct disciplines, operate under separate sets of laws and regulations. Environmental laws encompass multilateral environmental agreements, and regional and national regulations, while trading activities are governed by the multilateral agreements of the World Trade Organization (WTO) and bilateral agreements. The integration of international trade with environmental measures has become a contentious subject. Proponents of trade argue that it facilitates global access to environment-friendly goods and technologies, thereby facilitating the maintenance of high environmental standards. In contrast, environmentalists contend that international trade laws and practices often impede the governmental efforts to implement regulatory measures aimed at pollution prevention and environmental restoration. The WTO has faced criticism for its perceived inaction in addressing environmental concerns ensuing from trade, despite acknowledging environmental protection as an objective in the preamble of the Marrakesh Agreement. The global discourse on environmental protection has intensified, seeking to accord environmental issues the same weight as trade disputes. This article endeavours to delve into the multifaceted interactions between international trade and environmental protection, scrutinizing their regulatory mechanisms while highlighting the underlying grounds for the disputes that arise between these two realms. Agreement on Fisheries subsidies, Committee on Trade and Environment, Environmental Protection, Free Trade, GATT, Multilateral Environmental Agreements, WTO

Diterpenoid honatisine overcomes temozolomide resistance in glioblastoma by inducing mitonuclear protein imbalance through disruption of TFAM-mediated mtDNA transcription

BackgroundGlioblastoma (GBM) represents as the most formidable intracranial malignancy. The systematic exploration of natural compounds for their potential applications in GBM therapy has emerged as a pivotal and fruitful avenue of research. PurposeIn the present study, a panel of 96 diterpenoids was systematically evaluated as a repository of potential antitumour agents. The primary objective was to discern their potency in overcoming resistance to temozolomide (TMZ). Through an extensive screening process, honatisine, a heptacyclic diterpenoid alkaloid, emerged as the most robust candidate. Notably, honatisine exhibited remarkable efficacy in patient-derived primary and recurrent GBM strains. Subsequently, we subjected this compound to comprehensive scrutiny, encompassing GBM cultured spheres, GBM organoids (GBOs), TMZ-resistant GBM cell lines, and orthotopic xenograft mouse models of GBM cells. ResultsOur investigative efforts delved into the mechanistic underpinnings of honatisine's impact. It was discerned that honatisine prompted mitonuclear protein imbalance and elicited the mitochondrial unfolded protein response (UPRmt). This effect was mediated through the selective depletion of mitochondrial DNA (mtDNA)-encoded subunits, with a particular emphasis on the diminution of mitochondrial transcription factor A (TFAM). The ultimate outcome was the instigation of deleterious mitochondrial dysfunction, culminating in apoptosis. Molecular docking and surface plasmon resonance (SPR) experiments validated honatisine's binding affinity to TFAM within its HMG-box B domain. This binding may promote phosphorylation of TFAM and obstruct the interaction of TFAM bound to heavy strand promoter 1 (HSP1), thereby enhancing Lon-mediated TFAM degradation. Finally, in vivo experiments confirmed honatisine's antiglioma properties. Our comprehensive toxicological assessments underscored its mild toxicity profile, emphasizing the necessity for a thorough evaluation of honatisine as a novel antiglioma agent. ConclusionIn summary, our data provide new insights into the therapeutic mechanisms underlying honatisine's selective inducetion of apoptosis and its ability to overcome chemotherapy resistance in GBM. These actions are mediated through the disruption of mitochondrial proteostasis and function, achieved by the inhibition of TFAM-mediated mtDNA transcription. This study highlights honatisine's potential as a promising agent for glioblastoma therapy, underscoring the need for further exploration and investigation.

Team Primary Care: Training for Transformation in Canada

To address the growing crisis in primary care access and sustainability in Canada, Team Primary Care brings together 65+ health professional organizations to enhance the capacity of interprofessional, comprehensive primary care through improved training for practitioners, supports for teams and tools for planners and employers.
 Team Primary Care targets the primary care workforce including family physicians, primary care nurse practitioners, family practice nurses, pharmacists, physician assistants, mental health practitioners, traditional Indigenous Healers, and others. The project focuses on those involved in the training of the primary care workforce, including funders, accreditors, learning organizations, health professional associations and government.
 Team Primary Care endeavours to enhance interprofessional comprehensive primary care training; improve labour market integration for Indigenous and internationally educated practitioners, maximizing their utilization; create enabling environments for diverse, healthy, and resilient team members to practice at their optimal scope and capacity; and demonstrate, spread and scale leading integrated primary care workforce planning practices, tools, and resources.
 To date, Team Primary Care has launched eight primary care practitioner specific curricular development projects in parallel with workplace integrated learning demonstration projects, offered team-based training for primary care teams using cross cutting tools and supports to enhance interprofessional, equitable and inclusive, culturally safe care aimed at improving access to care and provider well-being. By March 2023 we anticipate an additional 12 curricular projects and 20+ demonstration projects will be ready for implementation. Unique to this project is its integrative approach and intentional change strategy that has been embedded in its design. In addition, an extensive process, outcome, and meta evaluation will have been carried out throughout the length of the project. Between now and March 2023, the aim is for the project to enhance primary care capacity enabling more Canadians to have access to an integrated primary care workforce that is inclusive of a broader range of practitioners working in teams that embed the principles of interprofessionalism, equity, diversity, inclusion, accessibility, psychological health and safety, reconciliation, and social accountability through enhanced and aligned training.
 The integrative and inclusive approach taken by Team Primary Care provides a unique country-wide case study of how to rapidly use education as a vehicle to quickly catalyze practice reform in primary care. Shifting the mental model towards team-based care inclusive of a broad range of primacy care practitioners committed to the delivery of comprehensive primary care was a major focus of the communication plan used. The cross-cutting tools developed are transferable to teams included but not limited to primary care and for both the Canadian context and beyond.
 The development of a sustainable interprofessional primary care training table is envisioned with a repository of team training tools and resources for use by a prepared primary care workforce prepared to scale and spread team-based care across the healthcare system. This case study will offer learned lessons on how education can be a critical enabler for primary care system reform.

How do Employees Experience Digital Monitoring and Coaching to Better Cope with Their Pain: A Pilot Study with a Smartphone Application

Background: Pain complaints are an important problem for employees, employers, and society. Up to 60% of the working population suffers from pain and these complaints are responsible for a third of all absenteeism. Pain is a complex phenomenon influenced by physical and psychosocial factors. Digital technologies such as smartphone applications offer opportunities to empower employees and help them manage and cope with their pain. However, lack of empirical evidence and user-friendly design hinder the adoption of these technologies in practice. This one group open label pilot aimed at evaluating the impact and user experience of an innovative smartphone application that includes monitoring as well as coaching to help employees manage their pain.
 Methods: An extensive co-design process including 262 end-users and seven domain experts was used to develop an app that contains 1) a monitoring part with questionnaires and integration with an activity tracker and 2) a coaching part including online information and exercises to help improve pain-related cognitions and other pain-management skills. Afterwards, 66 employees (experiencing pain for at least six weeks) of a large Belgian hospital used the smartphone app for six months. Every six weeks, participants were asked to complete a standardized questionnaire measuring work expectations, pain-related perceptions, and pain behavior. Finally, 12 employees participated in a semi-structured interview to help understand the quantitative findings, evaluate the user experience, and formulate recommendations towards the use of pain-management apps for employees. Quantitative and qualitative analyses by means of SPSS (version 28.0.1.0) and NVivo (version 1.0) were conducted to test the hypotheses. 
 Results: Forty-eight participants had complaints, mostly located in the back (80%) and neck (74%), for at least one year. Only pain catastrophizing (χ2=15.934, p = .001) and fear avoidance (χ2=8.934, p = .030) were improved after using the app for six months. Participants experienced the app as useful and well elaborated. Based on the thematic analysis, seven recommendations emerged: 1) awareness and education about pain and pain perceptions stimulates behavior change, but make sure that the focus is on coping with pain and valued activities and not on the pain itself, 2) monitoring should be user friendly, accurate, and relevant, 3) the ability to explore and learn at your own pace is a must, 4) app functionalities should be attractive and provide maximal reward while requiring minimal effort from the user, 5) personalized and job-specific content is a must, 6) a blended approach, i.e. digital tools combined with human contact with a professional expert, is recommended, and 7) integration within a broader well-being policy at work is required.
 Conclusion: A smartphone application may help employees to monitor and cope with their pain at work. Provided that it meets some specific requirements: 1) an app is not used as a standalone but integrated within a broader wellbeing policy at work, 2) there is the possibility to interact with a professional, and 3) an app contains personal and job-specific recommendations tailored to the workplace and specific needs of the user.