We know that we don't know: Children's understanding of common ignorance in a coordination game.

Common ground is the knowledge, beliefs, and suppositions shared between partners in an interaction. Previous research has focused extensively on what partners know they know together, that is, "common knowledge." However, another important aspect of common ground is what partners know they do not know together, that is, "common ignorance." A new coordination game was designed to investigate children's use of common ignorance. Without communicating or seeing each other's decisions, 4- to 8-year-olds needed to make the same decision as their partner about whether to try to retrieve a reward. To retrieve it, at least one of them needed to know a secret code. The knowledge/ignorance of both partners was ostensively manipulated by showing one partner, both partners, or neither partner the secret code in four conditions: common knowledge (both knew the code), common ignorance (neither partner knew the code), common privileged self knowledge (only children knew the code), and common privileged other knowledge (only their partner knew the code). Children's decisions, latency, and uncertainty were coded. Results showed that the common ignorance states were generally more difficult than the common knowledge states. Unexpectedly, children at all ages had difficulty with coordinating when their partner knew the code but they themselves did not (common privileged other knowledge). This study shows that, along with common knowledge, common ignorance and common privileged self knowledge and other knowledge also play important roles in coordinating with others but may develop differently.

A predator-prey fractional model with disease in the prey species.

In this paper, we study a generalized eco-epidemiological model of fractional order for the predator-prey type in the presence of an infectious disease in the prey. The proposed model considers that the disease infects the prey, causing them to be divided into two classes, susceptible prey and infected prey, with different density-dependent predation rates between the two classes. We propose logistic growth in both the prey and predator populations, and we also propose that the predators have alternative food sources (i.e., they do not feed exclusively on these prey). The model is evaluated from the perspective of the global and local generalized derivatives by using the generalized Caputo derivative and the generalized conformable derivative. The existence, uniqueness, non-negativity, and boundedness of the solutions of fractional order systems are demonstrated for the classical Caputo derivative. In addition, we study the stability of the equilibrium points of the model and the asymptotic behavior of its solution by using the Routh-Hurwitz stability criteria and the Matignon condition. Numerical simulations of the system are presented for both approaches (the classical Caputo derivative and the conformable Khalil derivative), and the results are compared with those obtained from the model with integro-differential equations. Finally, it is shown numerically that the introduction of a predator population in a susceptible-infectious system can help to control the spread of an infectious disease in the susceptible and infected prey population.

Systematic computational hunting for small RNAs derived from ncRNAs during dengue virus infection in endothelial HMEC-1 cells.

In recent years, a population of small RNA fragments derived from non-coding RNAs (sfd-RNAs) has gained significant interest due to its functional and structural resemblance to miRNAs, adding another level of complexity to our comprehension of small-RNA-mediated gene regulation. Despite this, scientists need more tools to test the differential expression of sfd-RNAs since the current methods to detect miRNAs may not be directly applied to them. The primary reasons are the lack of accurate small RNA and ncRNA annotation, the multi-mapping read (MMR) placement, and the multicopy nature of ncRNAs in the human genome. To solve these issues, a methodology that allows the detection of differentially expressed sfd-RNAs, including canonical miRNAs, by using an integrated copy-number-corrected ncRNA annotation was implemented. This approach was coupled with sixteen different computational strategies composed of combinations of four aligners and four normalization methods to provide a rank-order of prediction for each differentially expressed sfd-RNA. By systematically addressing the three main problems, we could detect differentially expressed miRNAs and sfd-RNAs in dengue virus-infected human dermal microvascular endothelial cells. Although more biological evaluations are required, two molecular targets of the hsa-mir-103a and hsa-mir-494 (CDK5 and PI3/AKT) appear relevant for dengue virus (DENV) infections. Here, we performed a comprehensive annotation and differential expression analysis, which can be applied in other studies addressing the role of small fragment RNA populations derived from ncRNAs in virus infection.

Selection of software agile practices using Analytic hierarchy process.

Context: The increasing use of software and information technology in modern society requires that the deployment of IT solutions should be more efficient and controlled. In this sense, agile methodologies are essential to achieve this goal, but a relevant question arises: Which is the right methodology for reaching that goal? Objective: The purpose of the research was to study the prioritization of agile practices and improvement objectives in the context of software development, using the Analytic Hierarchy Process (AHP) method. For this purpose, 42 agile practices, 16 improvement objectives, 4 organizations dedicated to software development in Colombia and 40 professionals in the area of information and communication technologies in the same country were considered. Method: ology: The methodological approach used was mixed. On the one hand, we applied a quantitative approach for the treatment of data with the AHP method and, on the other hand, a qualitative analysis by consulting experts through a digital survey to validate the prioritization of the improvement objectives. Questionpro was used as a support tool for multicriteria comparison. Results: The main results show that applying AHP allowed us to prioritize 6 improvement objectives and 5 agile practices, where it is highlighted that the prioritization does not discard the other objects of comparison but allows us to put into practice the prioritized elements to favor their progressive implementation. The non-prioritized elements could be part of future iterations of multicriteria comparison that go hand in hand with capacity development and organizational maturity models in the context of global software development. Conclusion: It is highlighted that, although there is evidence of the application of multi-criteria comparison methods in the software development industry, this work applies such methods in the context of four different agile methodologies, which translates into a precedent for the conformation of hybrid methodological approaches.

Correction: Escudero-Flórez et al. Dengue Virus Infection Alters Inter-Endothelial Junctions and Promotes Endothelial-Mesenchymal-Transition-like Changes in Human Microvascular Endothelial Cells. Viruses 2023, 15, 1437.

Ryan L [...].

Telepsychiatry: The future is already present.

This review paper analyzes the state of knowledge on Telepsychiatry (TP) after the crisis caused by COVID and the resulting need to use new modalities of care. Six essential aspects of TP are addressed: patient's and mental health staff satisfaction, diagnostic reliability, effectiveness of TP interventions, cost-effectiveness in terms of opportunity cost (or efficiency), legal aspects inherent to confidentiality and privacy in particular and the attitude of professionals toward TP. Satisfaction with TP is acceptable among both patients and professionals, the latter being the most reluctant. Diagnostic reliability has been demonstrated, but requires further studies to confirm this reliability in different diagnoses and healthcare settings. The efficacy of TP treatments is not inferior to face-to-face care, as has been proven in specific psychotherapies. Finally, it should be noted that the attitude of the psychiatrist is the most decisive element that limits or facilitates the implementation of TP.

Dengue Virus Infection Alters Inter-Endothelial Junctions and Promotes Endothelial-Mesenchymal-Transition-Like Changes in Human Microvascular Endothelial Cells.

Dengue virus (DENV) is a pathogenic arbovirus that causes human disease. The most severe stage of the disease (severe dengue) is characterized by vascular leakage, hypovolemic shock, and organ failure. Endothelial dysfunction underlies these phenomena, but the causal mechanisms of endothelial dysfunction are poorly characterized. This study investigated the role of c-ABL kinase in DENV-induced endothelial dysfunction. Silencing c-ABL with artificial miRNA or targeting its catalytic activity with imatinib revealed that c-ABL is required for the early steps of DENV infection. DENV-2 infection and conditioned media from DENV-infected cells increased endothelial expression of c-ABL and CRKII phosphorylation, promoted expression of mesenchymal markers, e.g., vimentin and N-cadherin, and decreased the levels of endothelial-specific proteins, e.g., VE-cadherin and ZO-1. These effects were reverted by silencing or inhibiting c-ABL. As part of the acquisition of a mesenchymal phenotype, DENV infection and treatment with conditioned media from DENV-infected cells increased endothelial cell motility in a c-ABL-dependent manner. In conclusion, DENV infection promotes a c-ABL-dependent endothelial phenotypic change that leads to the loss of intercellular junctions and acquisition of motility.

Evaluating the Effect of a Telepsychiatry Educational Program on the Awareness, Knowledge, Attitude, and Skills of Telepsychiatry Among Spanish Psychiatrists during COVID-19 Pandemic.

Introduction: The COVID-19 pandemic has renewed the interest in telepsychiatry as a way to help psychiatrists care for their patients, but mental health providers' unfamiliarity and concerns may impede implementation of such services. This study aimed to determine the effect of an online educational intervention on awareness, knowledge, attitude, and skills (AKAS) of telepsychiatry among psychiatrists. Methods: The study used a pre-post-test design to compare AKAS of telepsychiatry among psychiatrists participating in an online course of practical telepsychiatry. The telemedicine AKAS questionnaire adapted to telepsychiatry was applied before and after the educational intervention, during the months of October to December 2020. Results: Responses from 213 participants were analyzed before the educational intervention and from 152 after it. The knowledge showed by Spanish psychiatrists before the educational intervention was good in 61% of participants, fair in 37%, and inadequate in 2%. With respect to attitudes toward telepsychiatry, 62% self-reported a high attitude, 33% moderate, and 5% low. With regard self-reported skills, 57% of the participating psychiatrists were highly skilled or experts, 22% moderately skilled, and 9% unskilled in handling telepsychiatry equipment. Despite the high baseline values, the educational intervention significantly improved psychiatrists' awareness, knowledge and attitudes toward telepsychiatry although not their skills. Conclusions: Online course of practical telepsychiatry was effective although future editions need to improve its focus on skills. This educational intervention represents an effort to promote the implementation of telepsychiatry as a health care alternative.

A new host-targeted antiviral cyclolignan (SAU-22.107) for Dengue Virus infection in cell cultures. Potential action mechanisms based on cell imaging.

Dengue virus (DENV) infection is the most arbovirosis in the world. However, medications have not been approved for its treatment. Drug discovery based on the host-targeted antiviral (HTA) constitutes a new promising strategy, considering their high genetic barrier to resistance and the low probability of selecting drug resistance strains. In this study, we have tested fifty-seven podophyllotoxin-related cyclolignans on DENV-2 infected cells and found the most promising compound was S.71. Using cellular and molecular biology experiments, we have discovered that the new lignan altered the distribution of microtubules, induced changes in cell morphology, and caused retraction of the rough endoplasmic reticulum. In addition, the compound alters the viral envelope protein and the double-stranded RNA, while there is a decrease in negative-strand RNA synthesis; especially when the compound was added between 6- and 12-hours post-infection. Altogether, S.71 decreases the viral yield through an HTA-related mechanism of action, possibly altering the DENV genome replication and/or polyprotein translation, through the alteration of microtubule distribution and endoplasmic reticulum deterioration. Finally, pharmacokinetic predictors show that S.71 falls within the standard ranges established for drugs.

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 2b Trial of P2X3 Receptor Antagonist Sivopixant for Refractory or Unexplained Chronic Cough.

INTRODUCTION: To determine the optimal dose of sivopixant, a highly selective P2X3 receptor antagonist, for refractory or unexplained chronic cough (RCC/UCC). METHODS: In this phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, patients received sivopixant 50, 150, or 300 mg or placebo once daily for 4 weeks. The primary endpoint was a change from baseline in 24-h cough frequency (coughs/h) with sivopixant vs placebo. RESULTS: Overall, 390/406 randomized patients completed the study. Placebo-adjusted changes in hourly cough count over 24 h were 13.17% (P = 0.3532), - 1.77% (P = 0.8935), and - 12.47% (P = 0.3241) and in cough severity (visual analog scale) were 1.75 mm (P = 0.5854), - 1.21 mm (P = 0.7056), and - 6.55 mm (P = 0.0433) with sivopixant 50, 150, and 300 mg, respectively. Placebo-adjusted changes from baseline in Leicester Cough Questionnaire total scores were - 0.37 (P = 0.4207), - 0.07 (P = 0.8806), and 0.69 (P = 0.1473) with sivopixant 50, 150, and 300 mg, respectively. Additionally, 61.3%, 78.3%, 86.8%, and 71.4% of patients receiving sivopixant 50, 150, and 300 mg and placebo, respectively, reported any improvements in Patient Global Impression of Change. The incidence of treatment-emergent adverse events (TEAEs) was 25.7%, 32.0%, 49.0%, and 20.6% in sivopixant 50, 150, and 300 mg and placebo groups, respectively; all TEAEs in the sivopixant group were mild-to-moderate. CONCLUSION: Sivopixant did not demonstrate a statistically significant difference vs placebo in change from baseline in 24-h cough frequency. The dose of 300 mg has potential for RCC/UCC, showing the greatest improvements in cough frequency and patient-reported outcomes and dose-related mild to moderate reversible taste disturbance, although further trials are needed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04110054; registered September 26, 2019.

[Peri-implantitis: current concepts about its etiology, clinical and imaging characteristics. A review]. / Periimplantitis: conceptos actuales sobre su etiología, características clínicas e imagenológicas. Una revisión.

Peri-implantitis (PI) is the inflammatory reaction of the peri-implant mucosa, accompanied by the progressive loss of supporting bone around the implant, which can compromise its stability, function and aesthetics. It is diagnosed by radiographic measurement of the alveolar bone level, with or without clinical symptoms of inflammation and a probing depth greater than 4 mm. The objective of this work was to review the scientific evidence on the prevalence, etiology, predisposing factors, clinical behavior and imaging characteristics of PI. An electronic search was carried out in Google Scholar, PubMed and Scielo, considering the period between 2010-2022, and a total of 40 articles were selected. It is concluded that the main etiological agent of PI is the biofilm, however, its appearance and severity may be associated with the presence of predisposing factors such as Diabetes Mellitus, smoking, pre-existing periodontal disease and absence of keratinized mucosa, among others. Clinically, PI is related to bleeding on probing, gingival recession, and suppuration. Imaging evaluation of the peri-implant defect is routinely performed with periapical radiographs; Recent use of cone-beam computed tomography has allowed three-dimensional assessment of the defect, although considerations of radiation dose to the patient and image artifacts have been made that may limit its extensive use.

The Colombian Zika Virus Isolate (COL345Si) Replicates in Prostate Adenocarcinoma Cells and Modulates the Antiviral Response.

Zika virus (ZIKV), a flavivirus that is mainly transmitted by A. aegypti and A. albopictus and sexual transmission, has been documented and described. The ZIKV RNA detection in the semen of vasectomized men indicates that accessory glands such as the prostate could be a site of virus replication. In this study, we characterized the ZIKV infection, evaluated the antiviral profile, and demonstrated the AXL and TIM-1 expression on the PC3 prostate cell line. It was also determined that PC3 cells are susceptible and permissive to ZIKV infection without altering the cell viability or causing a cytopathic effect. The antiviral profile suggests that the PC3 cells modulate the antiviral response through the suppressor molecule expression, SOCS-1, during a ZIKV infection.

Postoperative Liver Failure Secondary to Hypoxic Hepatitis in Double Lung Transplantation: A Case Report.

Hypoxic hepatitis is a diagnosis of exclusion that should be suspected in patients with systemic hypoperfusion risk factors. It has a very high mortality, close to 50%. Although respiratory failure has been described as an etiologic factor for hypoxic hepatitis, cases of liver failure secondary to hypoxic hepatitis after lung transplantation have not been reported. Here we describe the case of a 54-year-old patient who underwent double lung transplantation with intraoperative ECMO and presented postoperative liver failure with a fatal outcome, despite adequate functioning of the lung graft. We describe the clinical presentation, risk factors, intra- and postoperative course, diagnosis, and the importance of pretransplant assessment, along with a review of the literature.

RNA structure-altering mutations underlying positive selection on Spike protein reveal novel putative signatures to trace crossing host-species barriers in Betacoronavirus.

Similar to other RNA viruses, the emergence of Betacoronavirus relies on cross-species viral transmission, which requires careful health surveillance monitoring of protein-coding information as well as genome-wide analysis. Although the evolutionary jump from natural reservoirs to humans may be mainly traced-back by studying the effect that hotspot mutations have on viral proteins, it is largely unexplored if other impacts might emerge on the structured RNA genome of Betacoronavirus. In this survey, the protein-coding and viral genome architecture were simultaneously studied to uncover novel insights into cross-species horizontal transmission events. We analysed 1,252,952 viral genomes of SARS-CoV, MERS-CoV, and SARS-CoV-2 distributed across the world in bats, intermediate animals, and humans to build a new landscape of changes in the RNA viral genome. Phylogenetic analyses suggest that bat viruses are the most closely related to the time of most recent common ancestor of Betacoronavirus, and missense mutations in viral proteins, mainly in the S protein S1 subunit: SARS-CoV (G > T; A577S); MERS-CoV (C > T; S746R and C > T; N762A); and SARS-CoV-2 (A > G; D614G) appear to have driven viral diversification. We also found that codon sites under positive selection on S protein overlap with non-compensatory mutations that disrupt secondary RNA structures in the RNA genome complement. These findings provide pivotal factors that might be underlying the eventual jumping the species barrier from bats to intermediate hosts. Lastly, we discovered that nearly half of the Betacoronavirus genomes carry highly conserved RNA structures, and more than 90% of these RNA structures show negative selection signals, suggesting essential functions in the biology of Betacoronavirus that have not been investigated to date. Further research is needed on negatively selected RNA structures to scan for emerging functions like the potential of coding virus-derived small RNAs and to develop new candidate antiviral therapeutic strategies.

Applicability of inter-primer binding site iPBS- retrotransposon marker system for the assessment of genetic diversity and population structure of Peruvian rosewood (Aniba rosaeodora Ducke) germplasm.

BACKGROUND: Rosewood (Aniba rosaeodora Ducke), which has a great demand due to its essential oil globally, is an evergreen tree of the Amazon forests. Rosewood natural stands have been depleted through deforestation and the destruction of habitat. Currently, rosewood is included in the ICUN red list of endangered species. METHODS AND RESULTS: The 11 highly polymorphic primers amplified total 305 bands of which 301 (98.69%) were polymorphic. The number of effective alleles (Ne), Shannon's information index (I), overall gene diversity (Ht), gene diversity (h), and polymorphism information content (PIC) were (1.562), (0.505), (0.330), (0.337) and (0.343), respectively. These diversity indices explored high genetic diversity in rosewood germplasm. Among studied germplasm, the Santa Marta population was found most diverse by reflecting higher values of diversity indices while the Zungarococha population was found least diverse. The analysis of molecular variance (AMOVA) revealed that 79% of the genetic variation was within the populations. The STRUCTURE algorithm, unweighted pair group with arithmetic mean (UPGMA), and principal coordinate's analysis (PCoA) separated all germplasms into different population groups according to their geographic locations. Santa Marta population was found more diverse by reflecting higher values of diversity indices. The maximum genetic distance (0.868) was found between the Huajoya-10 and Nanay-3. In this investigation, iPBS- retrotransposon marker system was used to explore the genetic diversity of Peruvian rosewood germplasm. CONCLUSIONS: The results in this study such as higher genetic diversity indices, AMOVA (79%) within population and PIC value (0.343) showed the utility and reproducibility of iPBS-retrotransposons in this species successfully. The STRUCTURE algorithm separated the germplasms into six population groups according to their geographic locations. These results have valuable information for the conservation, management strategies and future breeding activities of rosewood.

Hígado y SARS-CoV-2: aspectos claves de la literatura / Liver and SARS-CoV-2: Literature key aspects

Resumen El nuevo coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2), virus que se ha expandido por todo el mundo, produce una infección respiratoria aguda capaz de producir la muerte; sin embargo, el daño en otros órganos también es frecuente. Diversos estudios han evidenciado alteraciones en pruebas de lesión hepáticas, las cuales se han asociado con enfermedad grave y mayor estancia hospitalaria; así mismo, en la infección por el virus en pacientes con enfermedad hepática preexistente se observó una elevación significativa de las aminotransferasas durante el curso de la enfermedad y mayor riesgo de enfermedad grave. La explicación fisiopatológica de la afectación hepática en estos pacientes abarca el efecto citopático directo producido por la unión del virus a la enzima convertidora de la angiotensina II (ECA-II) a los hepatocitos y colangiocitos, una respuesta inmunitaria desproporcionada y, en algunos casos, la hepatotoxicidad por medicamentos.

Abstract The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that has spread around the world, causes an acute respiratory infection and it may also cause death. The damage that can cause in other organs is frequent. Many studies had also shown alterations in liver function tests, that are then related to serious illness and with hospitalization requirements. Moreover, in patients infected with the virus that had underlying liver disease, a significant increase in the level of aminotransferases was observed in the course of the disease. A greater risk of serious illness was also detected. The pathophysiological explanation of liver injury in those patients covers the direct cytopathic effect produced by binding the virus, the angiotensin-converting enzyme (ACE2) to the hepatocytes and the cholangiocytes, excessive immune response, and in some cases, drug-induced hepatotoxicity.

Detección de la tuberculosis con algoritmos de Deep Learning en imágenes de radiografías del tórax / Tuberculosis detection with deep learning algorithms in chest X-ray images / Detecção de tuberculose com algoritmos de aprendizagem profunda em imagens de raio-X do tórax

Se estima que en 2019 murieron alrededor de 1,4 millones de personas infectadas por tuberculosis, gran parte de ellos en países en desarrollo. Si la tuberculosis se hubiera diagnosticado oportunamente se habría evitado la muerte de las personas infectadas. Uno de los métodos de detección de tuberculosis más relevante es el análisis de radiografías del tórax; sin embargo, contar con profesionales altamente capacitados para el diagnóstico de la tuberculosis en todos los centros de salud es imposible en los países emergentes, este es uno de los principales motivos de que este método no sea ampliamente usado. En las últimas décadas las redes neuronales han tenido un papel muy relevante en la solución de problemas de la sociedad y en especial en el sector salud. Se ha empleado tres algoritmos de aprendizaje profundo reconocidos en el desarrollo de visión computacional que son VGG19, MobileNet e InceptionV3, se ha logrado obtener resultados muy auspiciosos para la detección de la tuberculosis. Caso especial ha sido MobileNet que ha destacado entre las demás, dando resultados importantes en las diferentes métricas de evaluación empleadas. Además, MobileNet cuenta con una arquitectura menos compleja y los pesos obtenidos después del entrenamiento son muy menores en comparación de los otros dos algoritmos. Se concluye que MobileNet es el algoritmo de Deep Learning más eficiente a comparación de VGG19 e InceptionV3, cuenta con mejor precisión para la detección de la tuberculosis y; el costo computación y tiempo de procesamiento es significativamente menor.

It is estimated that around 1.4 million people infected with tuberculosis died in 2019, most of them in developing countries. If tuberculosis had been diagnosed in time, the death of infected people would have been prevented. One of the most relevant tuberculosis detection methods is the analysis of chest radiographs; However, having highly trained professionals for the diagnosis of tuberculosis in all health centers is impossible in emerging countries, this is one of the main reasons why this method is not widely used. In recent decades, neural networks have played a very relevant role in solving problems in society and especially in the health sector. Three recognized Deep Learning algorithms have been used in the development of computational vision that are VGG19, MobileNet and InceptionV3, it has been possible to obtain very auspicious results for the detection of tuberculosis. MobileNet has been a special case, which has stood out among the others, giving important results in the different evaluation metrics used. In addition, MobileNet has a less complex architecture and the weights obtained after training are very less compared to the other two algorithms. It is concluded that MobileNet is the most efficient Deep Learning algorithm compared to VGG19 and InceptionV3, it has better precision for the detection of tuberculosis and the computational cost and processing time is significantly lower.

Estima-se que cerca de 1,4 milhão de pessoas infectadas com tuberculose morreram em 2019, a maioria delas em países em desenvolvimento. Se a tuberculose tivesse sido diagnosticada a tempo, a morte de pessoas infectadas teria sido evitada. Um dos métodos de detecção de tuberculose mais relevantes é a análise de radiografias de tórax; No entanto, ter profissionais altamente capacitados para o diagnóstico da tuberculose em todos os centros de saúde é impossível nos países emergentes, esse é um dos principais motivos pelo qual esse método não é amplamente utilizado. Nas últimas décadas, as redes neurais têm desempenhado um papel muito relevante na resolução de problemas na sociedade e principalmente no setor da saúde. Três algoritmos de aprendizado profundo reconhecidos foram usados no desenvolvimento da visão computacional que são VGG19, MobileNet e InceptionV3, sendo possível obter resultados muito auspiciosos para a detecção da tuberculose. A MobileNet tem sido um caso especial, que tem se destacado entre os demais, apresentando resultados importantes nas diferentes métricas de avaliação utilizadas. Além disso, o MobileNet possui uma arquitetura menos complexa e os pesos obtidos após o treinamento são muito menores em comparação com os outros dois algoritmos. Conclui-se que o MobileNet é o algoritmo de aprendizado profundo mais eficiente em comparação ao VGG19 e ao InceptionV3, possui melhor precisão para detecção de tuberculose e; o custo de computação e o tempo de processamento são significativamente menores.

Hemodynamic outcomes after valve-in-valve transcatheter aortic valve replacement: a single-center experience.

BACKGROUND: Valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) has emerged as a safe, effective alternative to redo aortic valve surgery in high-risk patients with degenerated surgical bioprosthetic valves. However, ViV-TAVR has been associated high postprocedural valvular gradients, compared with TAVR for native-valve aortic stenosis. METHODS: We performed a retrospective study of all patients who underwent ViV-TAVR for a degenerated aortic valve bioprosthesis between January 1, 2013 and March 31, 2019 at our center. The primary outcome was postprocedural mean aortic valve gradient. Outcomes were compared across surgical valve type (stented versus stentless), surgical valve internal diameter (≤19 versus >19 mm), and transcatheter aortic valve type (self-expanding vs. balloon-expandable). RESULTS: Overall, 89 patients underwent ViV-TAVR. Mean age was 69.0±12.6 years, 61% were male, and median Society of Thoracic Surgeons Predicted Risk of Mortality score was 5.4 [interquartile range, 3.2-8.5]. Bioprosthesis mode of failure was stenotic (58% of patients), regurgitant (24%), or mixed (18%). The surgical valve was stented in 75% of patients and stentless in 25%. The surgical valve's internal diameter was ≤19 mm in 45% of cases. A balloon-expandable transcatheter valve was used in 53% of procedures. Baseline aortic valve area and mean gradients were 0.87±0.31 cm2 and 36±18 mmHg, respectively. These improved after ViV-TAVR to 1.38±0.55 cm2 and 18±11 mmHg at a median outpatient follow-up of 331 [67-394] days. Higher postprocedural mean gradients were associated with surgical valves having an internal diameter ≤19 mm (24±13 versus 16±8, P=0.002) and with stented surgical valves (22±11 versus 12±6, P<0.001). CONCLUSIONS: ViV-TAVR is an effective option for treating degenerated surgical aortic bioprostheses, with acceptable hemodynamic outcomes. Small surgical valves and stented surgical valves are associated with higher postprocedural gradients.

An Integrated View of Virus-Triggered Cellular Plasticity Using Boolean Networks.

Virus-related mortality and morbidity are due to cell/tissue damage caused by replicative pressure and resource exhaustion, e.g., HBV or HIV; exaggerated immune responses, e.g., SARS-CoV-2; and cancer, e.g., EBV or HPV. In this context, oncogenic and other types of viruses drive genetic and epigenetic changes that expand the tumorigenic program, including modifications to the ability of cancer cells to migrate. The best-characterized group of changes is collectively known as the epithelial-mesenchymal transition, or EMT. This is a complex phenomenon classically described using biochemistry, cell biology and genetics. However, these methods require enormous, often slow, efforts to identify and validate novel therapeutic targets. Systems biology can complement and accelerate discoveries in this field. One example of such an approach is Boolean networks, which make complex biological problems tractable by modeling data ("nodes") connected by logical operators. Here, we focus on virus-induced cellular plasticity and cell reprogramming in mammals, and how Boolean networks could provide novel insights into the ability of some viruses to trigger uncontrolled cell proliferation and EMT, two key hallmarks of cancer.