Inferring cancer progression from Single-Cell Sequencing while allowing mutation losses.

MOTIVATION: In recent years, the well-known Infinite Sites Assumption has been a fundamental feature of computational methods devised for reconstructing tumor phylogenies and inferring cancer progressions. However, recent studies leveraging single-cell sequencing (SCS) techniques have shown evidence of the widespread recurrence and, especially, loss of mutations in several tumor samples. While there exist established computational methods that infer phylogenies with mutation losses, there remain some advancements to be made. RESULTS: We present Simulated Annealing Single-Cell inference (SASC): a new and robust approach based on simulated annealing for the inference of cancer progression from SCS datasets. In particular, we introduce an extension of the model of evolution where mutations are only accumulated, by allowing also a limited amount of mutation loss in the evolutionary history of the tumor: the Dollo-k model. We demonstrate that SASC achieves high levels of accuracy when tested on both simulated and real datasets and in comparison with some other available methods. AVAILABILITY AND IMPLEMENTATION: The SASC tool is open source and available at https://github.com/sciccolella/sasc. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[Mental Health Global Action Programme (mhGAP) in Chile: Lessons Learned and Challenges for Latin America and the CaribbeanPrograma de ação mundial para reduzir as lacunas em saúde mental (mhGAP) no Chile: aprendizados e desafios para América Latina e Caribe]. / Programa de Acción Mundial para Superar las Brechas en Salud Mental (mhGAP) en Chile: aprendizajes y desafíos para América Latina y el Caribe.

OBJECTIVES: Present the methodology for comprehensive evaluation of the implementation of the Mental Health Global Action Programme (mhGAP) in Chile and describe the program's results. METHODS: Cross-sectional evaluative study based on a survey of key program informants deployed in 29 public health services in the country, as well as individual interviews and focus groups with key actors and experts. The evaluation was focused on the relevance and impact of mhGAP on the provision of mental health services and on the implementation of the program. RESULTS: The participants gave a positive evaluation of the progressive implementation of mhGAP in Chile. In particular: 1) They reported having better tools for detecting, diagnosing, and treating common disorders, and efficient referral strategies; (2) They rated all modules as important, the most relevant being self-harm/suicide (x¯ = 4.77) and mental and behavioral disorders in children and adolescents (x¯ = 4.58); (3) They favorably assessed the National Mental Health Day training courses and the subsequent courses repeated at the local level, indicating that these courses contributed to successful implementation of mhGAP; (4) They agreed on the need to incorporate new actors, strengthen certain aspects, and expand information on the program. CONCLUSIONS: The implementation of mhGAP in Chile is an emblematic example of learning supported by the development of community mental health and family health, among other factors. These accomplishments offer a unique opportunity to continue advancing the implementation of this program in the country and to implement this experience in other contexts in Latin America and the Caribbean.

OBJETIVOS: Apresentar a metodologia de avaliação completa da implementação do Programa de ação mundial para reduzir as lacunas em saúde mental (Mental Health GAP, mhGAP) no Chile e descrever seus resultados. MÉTODOS: Estudo avaliativo transversal baseado em levantamento realizado com profissionais de referência do programa, distribuídos em 29 serviços de saúde da rede pública do país, e entrevistas individuais e grupos focais com as principais partes interessadas e especialistas. O enfoque da avaliação foi a relevância e o impacto do mhGAP na prestação de serviços de saúde mental e a implementação do programa. RESULTADOS: Os participantes do estudo avaliaram positivamente a implementação progressiva do mhGAP no Chile. Em particular, 1) eles afirmaram possuir recursos melhores para detecção, diagnóstico e tratamento de transtornos frequentes e estratégias de encaminhamento eficientes; 2) classificaram todos os módulos como importantes, com destaque a autoagressão/suicídio (x¯ = 4,77) e transtornos mentais e de comportamento em crianças e adolescentes (x¯ = 4,58); 3) avaliaram de forma favorável a realização das Jornadas Nacionais de Saúde Mental e suas iterações em nível local contribuindo ao sucesso da implementação do mhGAP e 4) concordaram com a necessidade de atrair mais interessados, reforçar alguns aspectos e ampliar a divulgação do programa. CONCLUSÕES: A implementação do mhGAP no Chile é um caso emblemático de aprendizado apoiado no avanço da saúde mental comunitária e saúde da família, entre outros fatores. Esta conquista cria uma oportunidade única para continuar a expandir a implementação do programa no país e disseminar esta experiência a outros contextos na América Latina e Caribe.

gpps: an ILP-based approach for inferring cancer progression with mutation losses from single cell data.

BACKGROUND: Cancer progression reconstruction is an important development stemming from the phylogenetics field. In this context, the reconstruction of the phylogeny representing the evolutionary history presents some peculiar aspects that depend on the technology used to obtain the data to analyze: Single Cell DNA Sequencing data have great specificity, but are affected by moderate false negative and missing value rates. Moreover, there has been some recent evidence of back mutations in cancer: this phenomenon is currently widely ignored. RESULTS: We present a new tool, gpps, that reconstructs a tumor phylogeny from Single Cell Sequencing data, allowing each mutation to be lost at most a fixed number of times. The General Parsimony Phylogeny from Single cell (gpps) tool is open source and available at https://github.com/AlgoLab/gpps . CONCLUSIONS: gpps provides new insights to the analysis of intra-tumor heterogeneity by proposing a new progression model to the field of cancer phylogeny reconstruction on Single Cell data.

Quantifying the non-equilibrium activity of an active colloid.

Active matter systems exhibit rich emergent behavior due to constant injection and dissipation of energy at the level of individual agents. Since these systems are far from equilibrium, their dynamics and energetics cannot be understood using the framework of equilibrium statistical mechanics. Recent developments in stochastic thermodynamics extend classical concepts of work, heat, and energy dissipation to fluctuating non-equilibrium systems. We use recent advances in experiment and theory to study the non-thermal dissipation of individual light-activated self-propelled colloidal particles. We focus on characterizing the transition from thermal to non-thermal fluctuations and show that energy dissipation rates on the order of ∼kBT s-1 are measurable from finite time series data.

[Analysis of Governance in the Implementation of the Chilean Community Mental Health ModelAnálise da governança na implementação do modelo comunitário de saúde mental no Chile]. / Análisis de la gobernanza en la implementación del modelo comunitario de salud mental en Chile.

This article describes and analyzes the role of governance in the development of the Chilean community mental health model. It describes and analyzes five dimensions of governance: 1) the implementation of a series of strategies to encourage the participation of users of mental health services has yielded limited results; 2) the implementation of three national mental health plans with the same strategic vision over the course of three decades has helped increase access to community care for people with mental illness and diminish the role of psychiatric hospitals; 3) the lack of a mental health law remains a challenge, although a series of laws and decrees has partially compensated for this; 4) financial resource allocation regulations, human resources education, and technical guidelines have helped improve access and the quality of care; and 5) the gradual development of a mental health information system has provided knowledge, primarily on access rates, treatment gaps, and geographical inequities. The Chilean experience confirms the importance of implementing a set of governance strategies and mechanisms to promote the development and operation of mental health services. The type of governance strategies and mechanisms can vary from country to country, depending on the context and windows of opportunity.

O presente artigo descreve e analisa o papel da governança no desenvolvimento do modelo de saúde mental comunitária no Chile. São descritas e analisadas cinco dimensões da governança: 1) o desenvolvimento de uma série de estratégias para favorecer a participação dos usuários de serviços de saúde mental não tem obtido resultados satisfatórios; 2) a implementação de três planos nacionais de saúde mental, com a mesma visão estratégica ao longo de três décadas, tem contribuído para melhorar a acessibilidade à atenção comunitária de indivíduos com doenças mentais e restringir o papel dos hospitais psiquiátricos; 3) a inexistência de uma legislação sobre saúde mental continua sendo um desafio, embora tenha sido em parte compensada por distintas leis e decretos; 4) as regulamentações para designação dos recursos financeiros, a capacitação de recursos humanos e as diretrizes técnicas têm servido para melhorar o acesso e a qualidade da atenção e 5) a construção progressiva de um sistema de informação em saúde mental tem possibilitado conhecer sobretudo o nível de acesso, as lacunas de tratamento e as desigualdades geográficas. A experiência chilena confirma a importância do uso de um conjunto de estratégias e mecanismos de governança para favorecer o desenvolvimento e o funcionamento dos serviços de saúde mental. Várias estratégias e os mecanismos de governança podem ser usados em cada país de acordo com o contexto e a janela de oportunidades.

Catecholaminergic Regulation of Learning Rate in a Dynamic Environment.

Adaptive behavior in a changing world requires flexibly adapting one's rate of learning to the rate of environmental change. Recent studies have examined the computational mechanisms by which various environmental factors determine the impact of new outcomes on existing beliefs (i.e., the 'learning rate'). However, the brain mechanisms, and in particular the neuromodulators, involved in this process are still largely unknown. The brain-wide neurophysiological effects of the catecholamines norepinephrine and dopamine on stimulus-evoked cortical responses suggest that the catecholamine systems are well positioned to regulate learning about environmental change, but more direct evidence for a role of this system is scant. Here, we report evidence from a study employing pharmacology, scalp electrophysiology and computational modeling (N = 32) that suggests an important role for catecholamines in learning rate regulation. We found that the P3 component of the EEG-an electrophysiological index of outcome-evoked phasic catecholamine release in the cortex-predicted learning rate, and formally mediated the effect of prediction-error magnitude on learning rate. P3 amplitude also mediated the effects of two computational variables-capturing the unexpectedness of an outcome and the uncertainty of a preexisting belief-on learning rate. Furthermore, a pharmacological manipulation of catecholamine activity affected learning rate following unanticipated task changes, in a way that depended on participants' baseline learning rate. Our findings provide converging evidence for a causal role of the human catecholamine systems in learning-rate regulation as a function of environmental change.

Mitral Valve Malignant Primary Tumor as a Surgical Emergency: Case Report.

Malignant primary tumors of the heart are among the most unusual forms of cancer. Cardiac malignancy accounts for about 20% of all primary cardiac tumors, with most arising from the atria and less frequently the ventricles; very unusual locations include the great vessels and the cardiac valves. A rare case is presented of a young female that arrived at the authors' emergency room in pulmonary edema and circulatory collapse secondary to a true tumor of the mitral leaflets that caused severe mitral valve stenosis. On pathological examination this proved to be a mitral leaflet angiosarcoma.

Mesenchymal stem cell-coated sutures enhance collagen depositions in sutured tissues.

Sutures are commonly used for surgical procedures and new sutures are being developed to improve wound healing. In the past decade, it has been extensively shown that mesenchymal stem cells (MSCs) have a wound healing potential. To benefit the overall wound healing process, we aimed to analyze the usage of pretreated sutures for improving the implantation of MSCs in the tissues. Our results firstly showed that suture pretreatments with gelatin, poly-L-lysine, and NaOH improved the adhesive strength of MSCs to sutures. These cells remained surrounding the sutured tissue and no significant phenotypic changes were found in those cells cultured onto pretreated sutures. In vivo experiments showed that the implantation of MSCs by suturing increases the collagen content in the sutured tissue. Moreover, proteomics analysis of secreted proteins showed that collagen alpha-1(I) chain was the most abundant collagen found. To our knowledge, this is the first report that aimed to improve the implantation of MSCs in tissue by suture pretreatments. Moreover, in vivo experiments suggest that MSC-coated sutures may enhance wound healing and tissue remodeling through the release of different collagen types being applicable for those patients that tend to have difficulty healing.

Replacing non-biomedical concepts improves embedding of biomedical concepts.

Objectives: Concept embeddings are low-dimensional vector representations of concepts such as MeSH:D009203 (Myocardial Infarction), whose similarity in the embedded vector space reflects their semantic similarity. Here, we test the hypothesis that non-biomedical concept synonym replacement can improve the quality of biomedical concepts embeddings. Materials and methods: We developed an approach that leverages WordNet to replace sets of synonyms with the most common representative of the synonym set. Results: We tested our approach on 1055 concept sets and found that, on average, the mean intracluster distance was reduced by 8% in the vector-space. Assuming that homophily of related concepts in the vector space is desirable, our approach tends to improve the quality of embeddings. Discussion and Conclusion: This pilot study shows that non-biomedical synonym replacement tends to improve the quality of embeddings of biomedical concepts using the Word2Vec algorithm. We have implemented our approach in a freely available Python package available at https://github.com/TheJacksonLaboratory/wn2vec .

Removal of Mo(VI), Pb(II), and Cu(II) from wastewater using electrospun cellulose acetate/chitosan biopolymer fibers.

Environmentally friendly polymers such as cellulose acetate (CA) and chitosan (CS) were used to obtain electrospun fibers for Cu2+, Pb2+, and Mo6+ capture. The solvents dichloromethane (DCM) and dimethylformamide (DMF) allowed the development of a surface area of 148 m2 g-1 for CA fibers and 113 m2 g-1 for cellulose acetate/chitosan (CA/CS) fibers. The fibers were characterized by IR-DRIFT, SEM, TEM, CO2 sorption isotherms at 273 K, Hg porosimetry, TGA, stress-strain tests, and XPS. The CA/CS fibers had a higher adsorption capacity than CA fibers without affecting their physicochemical properties. The capture capacity reached 102 mg g-1 for Cu2+, 49.3 mg g-1 for Pb2+, and 13.1 mg g-1 for Mo6+. Furthermore, optimal pH, adsorption times qt, and C0 were studied for the evaluation of kinetic models and adsorption isotherms. Finally, a proposal for adsorbate-adsorbent interactions is presented as a possible capture mechanism where, in the case of Mo6+, a computational study is presented. The results demonstrate the potential to evaluate the fibers in tailings wastewater from copper mining.

"We Followed their Lead": Exploring Relational Change and Support among Caregivers of Transgender and Gender Diverse Youth.

Transgender and gender diverse youth and young adults (TGDY) experience higher mental health morbidity, including self-harm, suicide ideation, and suicide attempts, as compared to cisgender peers. Support from family members is associated with improved mental health outcomes for TGDY. However, little is known about the process that caregivers who consider themselves supportive undergo and how caregiver-youth relationships evolve through a TGDY's gender journey. Through a reflexive thematic analysis of 14 interviews conducted with caregivers of TGDY from April-July 2022, we sought to understand how caregivers who considered themselves supportive of TGDY navigated shifting relationships with themselves, their children, and their communities. Applying theories of Ambiguous Loss and Thriving Through Relationships, findings coalesced around several themes including reflecting on change, re-negotiating interpersonal relationships, and educating through relationships. The gender journeys of TGDY required caregivers to navigate relationships with self (feeling loss and wrestling with worry for their child), negotiate relationships with others (disclosing to extended family and social networks), and educate themselves and others through relationships (connecting through personal narratives from other families, parents supporting parents, learning to advocate for their child). The process of caregivers learning to support their children was facilitated through profound intrapersonal and interpersonal reflection, connection, and community. Understanding this process is important to inform educational interventions and programs that help caregivers learn to support and advocate effectively for TGDY.

The promises of large language models for protein design and modeling.

The recent breakthroughs of Large Language Models (LLMs) in the context of natural language processing have opened the way to significant advances in protein research. Indeed, the relationships between human natural language and the "language of proteins" invite the application and adaptation of LLMs to protein modelling and design. Considering the impressive results of GPT-4 and other recently developed LLMs in processing, generating and translating human languages, we anticipate analogous results with the language of proteins. Indeed, protein language models have been already trained to accurately predict protein properties, generate novel functionally characterized proteins, achieving state-of-the-art results. In this paper we discuss the promises and the open challenges raised by this novel and exciting research area, and we propose our perspective on how LLMs will affect protein modeling and design.

Global health reciprocal innovation to address mental health and well-being: strategies used and lessons learnt.

Over the past two decades there have been major advances in the development of interventions promoting mental health and well-being in low- and middle-income countries (LMIC), including delivery of care by non-specialist providers, incorporation of mobile technologies and development of multilevel community-based interventions. Growing inequities in mental health have led to calls to adopt similar strategies in high-income countries (HIC), learning from LMIC. To overcome shared challenges, it is crucial for projects implementing these strategies in different global settings to learn from one another. Our objective was to examine cases in which mental health and well-being interventions originating in or conceived for LMIC were implemented in the USA. The cases included delivery of psychological interventions by non-specialists, HIV-related stigma reduction programmes, substance use mitigation strategies and interventions to promote parenting skills and family functioning. We summarise commonly used strategies, barriers, benefits and lessons learnt for the transfer of these innovative practices among LMIC and HIC. Common strategies included intervention delivery by non-specialists and use of digital modalities to facilitate training and increase reach. Common barriers included lack of reimbursement mechanisms for care delivered by non-specialists and resistance from professional societies. Despite US investigators' involvement in most of the original research in LMIC, only a few cases directly involved LMIC researchers in US implementation. In order to achieve greater equity in global mental health and well-being, more efforts and targeted funding are needed to develop best practices for global health reciprocal innovation and iterative learning in HIC and LMIC.

[Description of a telehealth mental health programme in the framework of the COVID-19 pandemic in Colombia]. / Descripción de un programa de telesalud mental en el marco de la pandemia de COVID-19 en Colombia.

Background: A telehealth mental health programme was designed at the LivingLab of the Faculty of Medicine of the Universidad de Antioquia [University of Antioquia].Objectives: To describe the development and operation of the programme and evaluate the satisfaction of the patients treated during the COVID-19 pandemic in 2020 and 2021.Methods: Descriptive study that details the development of the programme. Data were extracted from medical records to describe the patients who were treated. A satisfaction scale was applied to a random sample and the data were summarised with descriptive statistics.Results: In March 2020 and August 2021, 10,229 patients were treated, with 20,276 treated by telepsychology and 4,164 by psychiatry, 1,808 by telepsychiatry and 2,356 by tele-expertise, with a total of 6,312 visits. The most frequent diagnoses were depressive (36.8%), anxiety (12.0%), and psychotic (10.7%) disorders. Respondents were satisfied to the point that more than 93% would recommend it to another person.Conclusions: The LivingLab telehealth mental health programme allowed for the care of patients with mental health problems and disorders in Antioquia during the first two years of the COVID-19 pandemic, and there was a high degree of satisfaction among the beneficiaries. Therefore it could be adopted in mental health care.

Serving young children with communication disabilities from Latinx backgrounds and their families with equity: Provider perspectives.

INTRODUCTION: Latinx children with communication disorders from birth to age 5 and their families are increasingly served in United States (US) educational and medical settings where longstanding structural barriers threaten their access to equitable assessment and intervention. However, little is known about providers' perceptions serving this highly diverse population as they relate to reducing disparities in care for communication disorders. METHODS: This exploratory qualitative study interviewed 24 speech-language pathologists (SLPs) and early intervention (EI)/early childhood special education (ECSE) developmental specialists serving young Latinx children with communication disorders to offer targeted recommendations toward improving equity. The semi-structured interview included questions regarding communication assessment, diagnostics/eligibility, intervention, interpretation, translation, and solutions to enhance EI/ECSE. Interviews were coded with content analysis using elements of grounded theory, and responses from SLPs in medical versus education settings and from EI/ECSE developmental specialists were compared. Data triangulation was used to validate themes. RESULTS: Analysis revealed the following themes related to provider challenges and resources: family factors, provider factors, cultural and linguistic differences, assessment approaches, eligibility determinations, translation and interpretation, and institutional factors. Few variations in themes between provider types (SLPs vs. EI/ECSE developmental specialists) and settings (medical vs. educational) were found. Providers also offered several policy and practice solutions. CONCLUSIONS: Findings suggest minimal advances in improving equity for young Latinx children with communication disorders over prior decades. Results also indicate that providers may benefit from reflecting on their cultures and biases as well as systemic racism within EI/ECSE.

OnTrack Chile for people with early psychosis: a study protocol for a Hybrid Type 1 trial.

BACKGROUND: Substantial data from high-income countries support early interventions in the form of evidence-based Coordinated Specialty Care (CSC) for people experiencing First Episode Psychosis (FEP) to ameliorate symptoms and minimize disability. Chile is unique among Latin American countries in providing universal access to FEP services through a national FEP policy that mandates the identification of FEP individuals in primary care and guarantees delivery of community-based FEP treatments within a public health care system. Nonetheless, previous research has documented that FEP services currently provided at mental health clinics do not provide evidence-based approaches. This proposal aims to address this shortfall by first adapting OnTrackNY (OTNY), a CSC program currently being implemented across the USA, into OnTrackChile (OTCH), and then examine its effectiveness and implementation in Chile. METHODS: The Dynamic Adaptation Process will be used first to inform the adaptation and implementation of OTCH to the Chilean context. Then, a Hybrid Type 1 trial design will test its effectiveness and cost and evaluate its implementation using a cluster-randomized controlled trial (RCT) (N = 300 from 21 outpatient clinics). The OTCH program will be offered in half of these outpatient clinics to individuals ages 15-35. Usual care services will continue to be offered at the other clinics. Given the current COVID-19 pandemic, most research and intervention procedures will be conducted remotely. The study will engage participants over the course of 2 years, with assessments administered at enrollment, 12 months, and 24 months. Primary outcomes include implementation (fidelity, acceptability, and uptake) and service outcomes (person-centeredness, adherence, and retention). Secondary outcomes comprise participant-level outcomes such as symptoms, functioning, and recovery orientation. Over the course of the study, interviews and focus groups with stakeholders will be conducted to better understand the implementation of OTCH. DISCUSSION: Findings from this study will help determine the feasibility, effectiveness, and cost for delivering CSC services in Chile. Lessons learned about facilitators and barriers related to the implementation of the model could help inform the approach needed for these services to be further expanded throughout Latin America. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT04247711 . Registered 30 January 2020. TRIAL STATUS: The OTCH trial is currently recruiting participants. Recruitment started on March 1, 2021, and is expected to be completed by December 1, 2022. This is the first version of this protocol (5/12/2021).

Pancoast Syndrome Due to High Grade Anaplastic Tumor.

Description The Pancoast tumor is an uncommon type of lung cancer that arises from within the superior sulcus. With most clinical manifestations occurring due to mass effect, Pancoast syndrome is a known complication that includes shoulder and arm musculoskeletal pain, Horner's syndrome and neurological complications of the upper extremities, including weakness and atrophy. Even though adenocarcinoma is the most common cause of Pancoast syndrome among lung cancers, other malignancies can be responsible as well. Treatment is similar to that of other standard NSCLC treatments that include chemotherapy, radiation, immunotherapy and surgery. Here we report a patient with Pancoast syndrome secondary to a poorly differentiated malignant neoplasm composed of anaplastic cells.

Isolated contracture of the rectus femoris muscle: notification and review of the pathology regarding a case. / Contractura aislada del músculo recto femoral: notificación y revisión de la patología a propósito de un caso.

We described the case of a 12-year-old patient who presented isolated contracture of the left rectus femoris muscle with subsequent traumatic rupture of the distal myotendinous junction; for this reason she did not present contracture in extension of the knee but she presented dynamic contracture in flexion of the hip (Ely positive test), which generated great impact on walking. Surgical management with tenotomy of the anterior rectum was performed, obtaining good results. This pathology has low incidence and it has been reported little in the literature, so it is important to suspect it. We provide an updated diagnostic and therapeutic approach.

Stochastic force dynamics of the model microswimmer Chlamydomonas reinhardtii: Active forces and energetics.

We study the stochastic force dynamics of a model microswimmer (Chlamydomonas reinhardtii), using a combined experimental, theoretical, and numerical approach. While swimming dynamics have been extensively studied using hydrodynamic approaches, which infer forces from the viscous flow field, we directly measure the stochastic forces generated by the microswimmer using an optical trap via the photon momentum method. We analyze the force dynamics by modeling the microswimmer as a self-propelled particle, à la active matter, and analyze its energetics using methods from stochastic thermodynamics. We find complex oscillatory force dynamics and power dissipation on the order of 10^{6}k_{B}T/s(∼fW).

Intracoronary Delivery of Porcine Cardiac Progenitor Cells Overexpressing IGF-1 and HGF in a Pig Model of Sub-Acute Myocardial Infarction.

Human cardiac progenitor cells (hCPC) are considered a good candidate in cell therapy for ischemic heart disease, demonstrating capacity to improve functional recovery after myocardial infarction (MI), both in small and large preclinical animal models. However, improvements are required in terms of cell engraftment and efficacy. Based on previously published reports, insulin-growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) have demonstrated substantial cardioprotective, repair and regeneration activities, so they are good candidates to be evaluated in large animal model of MI. We have validated porcine cardiac progenitor cells (pCPC) and lentiviral vectors to overexpress IGF-1 (co-expressing eGFP) and HGF (co-expressing mCherry). pCPC were transduced and IGF1-eGFPpos and HGF-mCherrypos populations were purified by cell sorting and further expanded. Overexpression of IGF-1 has a limited impact on pCPC expression profile, whereas results indicated that pCPC-HGF-mCherry cultures could be counter selecting high expresser cells. In addition, pCPC-IGF1-eGFP showed a higher cardiogenic response, evaluated in co-cultures with decellularized extracellular matrix, compared with native pCPC or pCPC-HGF-mCherry. In vivo intracoronary co-administration of pCPC-IGF1-eGFP and pCPC-HFG-mCherry (1:1; 40 × 106/animal), one week after the induction of an MI model in swine, revealed no significant improvement in cardiac function.