Pathogenic Variants Associated with Epigenetic Control and the NOTCH Pathway Are Frequent in Classic Hodgkin Lymphoma.

Classic Hodgkin lymphoma (cHL) constitutes a B-cell neoplasm derived from germinal center lymphocytes. Despite high cure rates (80-90%) obtained with the current multiagent protocols, a significant proportion of cHL patients experience recurrences, characterized by a lower sensitivity to second-line treatments. The genomic background of chemorefractory cHL is still poorly understood, limiting personalized treatment strategies based on molecular features. In this study, using a targeted next-generation sequencing (NGS) panel specifically designed for cHL research, we compared chemosensitive and chemorefractory diagnostic tissue samples of cHL patients. Furthermore, we longitudinally examined paired diagnosis-relapsesamples of chemorefractory cHL in order to define patterns of dynamic evolution and clonal selection. Pathogenic variants in NOTCH1 and NOTCH2 genes frequently arise in cHL. Mutations in genes associated with epigenetic regulation (CREBBP and EP300) are particularly frequent in relapsed/refractory cHL. The appearance of novel clones characterized by mutations previously not identified at diagnosis is a common feature in cHL cases showing chemoresistance to frontline treatments. Our results expand current molecular and pathogenic knowledge of cHL and support the performance of molecular studies in cHL prior to the initiation of first-line therapies.

Tissue engineering in otorhinolaryngology: A knowledge-based analysis.

Objective: To analyze the impact, performance, degree of specialization, and collaboration patterns of the worldwide scientific production on tissue engineering in otorhinolaryngology at the level of countries and institutions. Methods: Two different techniques were used, performance and science mapping analyses, using as samples all the available documents regarding tissue engineering focused on otorhinolaryngology applications. The dataset was retrieved from the Core Collection of the Web of Science database from 1900 to 2020. Social structure was analyzed using science mapping analysis with VOSviewer software. Results: The United States was the main producer, followed by Germany, and Japan. Malaysia and Germany had the highest Relative Specialization Index, indicating their greater relative interest in this area compared to other countries. The social structure analysis showed that the United States and Germany had significant co-authorship relationships with other countries. The University of California System, Kyoto University, and Harvard University were the leading institutions producing literature in this field. These latter two institutions showed the largest number of collaborations, although most of them were with institutions within their own country. There was a lack of connections between different communities of research. Conclusion: The United States is the main country driving progress in this research area, housing the most notable institutions. However, significant collaborations between these research centers are currently lacking. Encouraging greater cooperation among these institutions and their researchers would promote the exchange of knowledge, ultimately facilitating and accelerating advancements in this field.

Estudio de variantes genéticas en 169 pacientes de cáncer de pulmón no microcítico / Study of genetic variants in 169 non-small cell lung cancer patients

Introducción: El cáncer de pulmón es la principal causa de muerte por cáncer en nuestro país. El cáncer de pulmón de células no pequeñas (CPCNP) representa el paradigma de la medicina personalizada. El objetivo principal de este trabajo es estudiar la frecuencia en nuestro medio de las variantes clínicamente significativas más frecuentemente descritas en CPCNP. Material y métodos: Se estudia la expresión inmunohistoquímica de TTF1, p40 y PD-L1 y la frecuencia de variantes genéticas mediante secuenciación masiva (NGS) con un panel de 52 genes, en 174 muestras incluidas en parafina de CPNCP en 169 pacientes (111 hombres y 52 mujeres) de la provincia de Cádiz. Resultados: La expresión inmunohistoquímica de TTF1, p40 y PD-L1 fue positiva en el 87%, el 0% y el 46% de los adenocarcinomas y en el 0%, el 100% y el 41% de los carcinomas escamosos. En NGS, las variantes de un solo nucleótido (SNV) más frecuentes fueron KRAS (36%), EGFR (14%), BRAF (10%), PIK3CA (8%) y MET (3%). Las variantes en el número de copias (CNV) más frecuentes fueron las amplificaciones en NF1 (30%), EGFR (18%), CCND1 (9%), MYC (9%) y KRAS (7%). En mujeres, las SNV en EGFR fueron más frecuentes que en hombres (p<0,0001). El adenocarcinoma es el tipo histológico más frecuente con SNV en KRAS (p=0,007361) o en EGFR (p<0,0001). En 16 pacientes (9,47%) se detectaron fusiones génicas, 9 casos en el gen MET. Conclusiones: Detectamos nuevas asociaciones entre expresión inmunohistoquímica y algunas variantes génicas, que podrían tener impacto en el tratamiento de pacientes de CPNCP.(AU)

Introduction: Lung cancer is the leading cause of cancer death in our country. Non-small cell lung cancer (NSCLC) represents the paradigm of personalized medicine. The main objective of this study is analysing the distribution of the most frequently described clinically significant variants in NSCLC, in our environment. Material and methods: We studied the immunohistochemical expression of TTF1, p40 and PD-L1 and the genetic variants frequency using Next-Generation Sequencing (NGS) with a panel of 52 genes, in 174 NSCLC paraffin-embedded samples in 169 patients (111 men and 52 women) from the province of Cádiz. Results: The immunohistochemical expression of TTF1, p40 and PD-L1 was positive in 87%, 0% and 46% in adenocarcinoma, and 0%, 100% and 41% in squamous cell carcinoma. In NGS, the most common single nucleotide variants (SNVs) were KRAS (36%), EGFR (14%), BRAF (10%), PIK3CA (8%), and MET (3%). The most frequent copy number variants (CNVs) were amplifications in NF1 (30%), EGFR (18%), CCND1 (9%), MYC (9%) and KRAS (7%). In women, SNV in EGFR are more frequent than in men (P<.0001). Adenocarcinoma is the most frequent histological type with SNV in KRAS (P=.007361) or in EGFR (P<.0001). Gene fusions were detected in 16 patients (9.47%), in 9 cases in the MET gene. Conclusions: We detected associations, not described so far, between immunohistochemical expression and specific gene variants, which could have an impact on the treatment of NSCLC patients.(AU)

Whole slide imaging of tumour microenvironment in classical Hodgkin's lymphoma: development of a clinical prediction model based on programmed death-ligand 1 and tumorous Reed-Sternberg cells.

AIMS: The prognostic impact of programmed death-ligand 1 (PD-L1) cells in classic Hodgkin lymphoma (cHL) tumour microenvironment remains undefined. METHODS: Model development via Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines were followed. PD-L1+ and CD30+ tumoral Reed-Sternberg cells were quantified through whole slide imaging and digital image analysis in 155 digital histopathological slides of cHL. Univariate and multivariate survival analyses were performed. The analyses were reproduced for patients with advanced stages (IIB, III and IV) using the Advanced-stage cHL International Prognostic Index. RESULTS: The PD-L1/CD30 ratio was statistically significantly associated with survival outcomes. Patients with a PD-L1/CD30 ratio above 47.1 presented a shorter overall survival (mean OS: 53.7 months; 95% CI: 28.7 to 78.7) in comparison with patients below this threshold (mean OS: 105.4 months; 95% CI: 89.6 to 121.3) (p=0.04). When adjusted for covariates, the PD-L1/CD30 ratio retained prognostic impact, both for the OS (HR: 1.005; 95% CI: 1.002 to 1.008; p=0.000) and the progression-free survival (HR: 3.442; 95% CI: 1.045 to 11.340; p=0.04) in a clinical and histopathological multivariate model including the male sex (HR: 3.551; 95% CI: 0.986 to 12.786; p=0.05), a percentage of tumoral cells ≥10.1% (HR: 1.044; 95% CI: 1.003 to 1.087; p=0.03) and high risk International Prognostic Score (≥3 points) (HR: 6.453; 95% CI: 1.970 to 21.134; p=0.002). CONCLUSIONS: The PD-L1/CD30 ratio identifies a group of cHL patients with an increased risk of treatment failure. Its clinical application can be performed as it constitutes an easy to implement pathological information in the diagnostic work-up of patients with cHL.

[Study of genetic variants in 169 non-small cell lung cancer patients]. / Estudio de variantes genéticas en 169 pacientes de cáncer de pulmón no microcítico.

INTRODUCTION: Lung cancer is the leading cause of cancer death in our country. Non-small cell lung cancer (NSCLC) represents the paradigm of personalized medicine. The main objective of this study is analysing the distribution of the most frequently described clinically significant variants in NSCLC, in our environment. MATERIAL AND METHODS: We studied the immunohistochemical expression of TTF1, p40 and PD-L1 and the genetic variants frequency using Next-Generation Sequencing (NGS) with a panel of 52 genes, in 174 NSCLC paraffin-embedded samples in 169 patients (111 men and 52 women) from the province of Cádiz. RESULTS: The immunohistochemical expression of TTF1, p40 and PD-L1 was positive in 87%, 0% and 46% in adenocarcinoma, and 0%, 100% and 41% in squamous cell carcinoma. In NGS, the most common single nucleotide variants (SNVs) were KRAS (36%), EGFR (14%), BRAF (10%), PIK3CA (8%), and MET (3%). The most frequent copy number variants (CNVs) were amplifications in NF1 (30%), EGFR (18%), CCND1 (9%), MYC (9%) and KRAS (7%). In women, SNV in EGFR are more frequent than in men (P<.0001). Adenocarcinoma is the most frequent histological type with SNV in KRAS (P=.007361) or in EGFR (P<.0001). Gene fusions were detected in 16 patients (9.47%), in 9 cases in the MET gene. CONCLUSIONS: We detected associations, not described so far, between immunohistochemical expression and specific gene variants, which could have an impact on the treatment of NSCLC patients.

Analysis of cognitive framework and biomedical translation of tissue engineering in otolaryngology.

Tissue engineering is a relatively recent research area aimed at developing artificial tissues that can restore, maintain, or even improve the anatomical and/or functional integrity of injured tissues. Otolaryngology, as a leading surgical specialty in head and neck surgery, is a candidate for the use of these advanced therapies and medicinal products developed. Nevertheless, a knowledge-based analysis of both areas together is still needed. The dataset was retrieved from the Web of Science database from 1900 to 2020. SciMAT software was used to perform the science mapping analysis and the data for the biomedical translation identification was obtained from the iCite platform. Regarding the analysis of the cognitive structure, we find consolidated research lines, such as the generation of cartilage for use as a graft in reconstructive surgery, reconstruction of microtia, or the closure of perforations of the tympanic membrane. This last research area occupies the most relevant clinical translation with the rest of the areas presenting a lower translational level. In conclusion, Tissue engineering is still in an early translational stage in otolaryngology, otology being the field where most advances have been achieved. Therefore, although otolaryngologists should play an active role in translational research in tissue engineering, greater multidisciplinary efforts are required to promote and encourage the translation of potential clinical applications of tissue engineering for routine clinical use.

Identification of histological threshold concepts in health sciences curricula: Students' perception.

Students' metacognitive skills and perceptions are considered important variables for high-quality learning. In this study, students' perceptions were used to identify histological threshold concepts (integrative, irreversible, transformative, and troublesome) in three health sciences curricula. A specific questionnaire was developed and validated to characterize students' perceptions of histological threshold concepts. A sample of 410 undergraduate students enrolled in the dentistry, medicine, and pharmacy degree programs participated in the study. Concepts assessed in the study were clustered to ten categories (factors) by exploratory and confirmatory factor analysis. Concepts linked to tissue organization and tissue functional states received the highest scores from students in all degree programs, suggesting that the process of learning histology requires the integration of both static concepts related to the constituent elements of tissues and dynamic concepts such as stem cells as a tissue renewal substrate, or the euplasic, proplasic and retroplasic states of tissues. The complexity of integrating static and dynamic concepts may pose a challenging barrier to the comprehension of histology. In addition, several differences were detected among the students in different degree programs. Dentistry students more often perceived morphostructural concepts as threshold concepts, whereas medical students highlighted concepts related to two-dimensional microscopic identification. Lastly, pharmacy students identified concepts related to tissue general activity as critical for the comprehension and learning of histology. The identification of threshold concepts through students' perceptions is potentially useful to improve the teaching and learning process in health sciences curricula.

Identification of prognostic factors in classic Hodgkin lymphoma by integrating whole slide imaging and next generation sequencing.

Digital pathology and genomics are increasingly used to improve our understanding of lymphoid neoplasms. Algorithms for quantifying cell populations in the lymph node and genetics can be integrated to identify new biomarkers with prognostic impact in classic Hodgkin lymphoma (cHL). In 16 cHL patients, we have performed whole slide imaging (WSI) analysis and quantification of CD30+, CD20+, CD3+ and MUM1+ cells in whole tissue slides, and Next Generation Sequencing (NGS) in formalin fixed paraffin-embedded (FFPE) tissue, using a widely used NSG panel (Oncomine® Focus Assay) to define genetic variants underlying tumor development. The different cell populations could be successfully identified in scanned slides of cHL, supporting the inclusion of WSI in the histopathological evaluation of cHL as an adequate method for the quantification of different cell populations. We also performed genetic profiling in FFPE samples of cHL leading to the identification of copy number variations in the Neurofibromin 1 gene (17q11.2) and the Androgen Receptor gene (Xq12) accompanied by chromosomal gains and losses in CDK4, KRAS and FGFR2 genes. Progression-free survival (PFS) was statistically significantly higher in cHL patients with amplification in the NF1 gene combined with CD3+ cells above 28.6% (p = 0.006) and MUM1+ cells above 21.8% (p < 0.001). Moreover, patients with MUM1+ cells above 21.8% showed a statistically significantly higher PFS when combined with amplification of the AR gene (p < 0.001) and wild-type KRAS (p < 0.001). The integration of WSI analysis and DNA sequencing could be useful to improve our understanding of the biology of cHL and define risk subgroups.

Whole-slide image analysis identifies a high content of Hodgkin Reed-Sternberg cells and a low content of T lymphocytes in tumor microenvironment as predictors of adverse outcome in patients with classic Hodgkin lymphoma treated with ABVD.

Classic Hodgkin lymphoma (cHL) constitutes the most frequent lymphoma in young adults. Its histopathology is unique as a scattered tumor population, termed Hodgkin Reed-Sternberg (HRS) cells is diluted in a prominent tumor microenvironment (TME) composed of T lymphocytes, B lymphocytes, macrophages, neutrophils, eosinophils and histiocytes. Traditionally, the identification of prognostic biomarkers in the cHL TME has required visual inspection and manual counting by pathologists. The advent of whole-slide imaging (WSI) and digital image analysis methods could significantly contribute to improve this essential objective in cHL research, as a 10-20% of patients are still refractory or relapsed after conventional chemotherapy. In this work, we have digitized a total of 255 diagnostic cHL slides and quantified the proportion of HRS cells (CD30), B cells (CD20) and T cells (CD3) by digital image analysis. Data obtained where then correlated with the overall survival (OS) and progression free survival (PFS) of cHL patients. Quantification of HRS cells, B cells and T cells reflects the biological heterogeneity of the different cHL histological subtypes analyzed. A percentage of 2.00% of HRS cells statistically significantly discriminated between patients achieving a complete metabolic response (CMR) and refractory or relapsed (R/R) patients both for the OS (P=0.001) and PFS (P=0.005). Furthermore, patients with a percentage of T cells below the 26.70% in the TME showed a statistically significantly shorter OS (P=0.019) and PFS (P=0.041) in comparison with patients above this threshold. A subgroup of patients with a low content of T cells and high content of HRS cells exhibited a special aggressive clinical course. Currently, there is the need to implement quantitative and easy scalable methods to enhance clinical translation, as the cHL TME plays a central role in the clinical course of the disease. The results of this study could contribute to the identification of prognostic biomarkers specifically looking at the cHL TME and their inclusion in future clinical trials.

Methods for identifying biomedical translation: a systematic review.

Translational medicine is an important area of biomedicine, and has significantly facilitated the development of biomedical research. Despite its relevance, there is no consensus on how to evaluate its progress and impact. A systematic review was carried out to identify all the methods to evaluate translational research. Seven methods were found according to the established criteria to analyze their characteristics, advantages, and limitations. They allow us to perform this type of evaluation in different ways. No relevant advantages were found between them; each one presented its specific limitations that need to be considered. Nevertheless, the Triangle of Biomedicine could be considered the most relevant method, concerning the time since its publication and usefulness. In conclusion, there is still a lack of a gold-standard method for evaluating biomedical translational research.

The Need for Standardization in Next-Generation Sequencing Studies for Classic Hodgkin Lymphoma: A Systematic Review.

Classic Hodgkin lymphoma (cHL) constitutes a B cell-derived neoplasm defined by a scarce tumoral population, termed Hodgkin and Reed-Sternberg (HRS) cells, submerged into a histologically heterogeneous microenvironment. The paucity of HRS cells has historically hampered genetic studies, rendering the identification of the recurrent genetic lesions and molecular pathways deregulated in this lymphoma difficult. The advent of high-throughput sequencing methods such as next-generation sequencing (NGS) could sensibly optimize the identification of the mutational landscape of cHL. However, there is no current consensus either in the design of panels for targeted NGS or in its most relevant clinical applications. In this work, we systematically review the current state of NGS studies of cHL, stressing the need for standardization both in the candidate genes to be analyzed and the bioinformatic pipelines. As different institutions have developed and implemented their own customized NGS-based protocols, to compare and systematically review the major findings of this ongoing research area could be of added value for centers that routinely perform diagnostic, monitoring and genotyping strategies in cHL samples. The results of this systematic review should contribute to the interdepartmental harmonization and achievement of a consensus in the current clinical applications of NGS studies of cHL.

Prognostic Role of the Expression of Latent-Membrane Protein 1 of Epstein-Barr Virus in Classical Hodgkin Lymphoma.

The prognostic impact of the presence of Epstein-Barr virus (EBV) in classical Hodgkin lymphoma (cHL) is controversial. Previous studies reported heterogeneous results, rendering difficult the clinical validation of EBV as a prognostic biomarker in this lymphoma. The objective of this study was to evaluate the survival impact of the expression of EBV Latent-Membrane Protein 1 (EBV-LMP1) in tumoral Hodgkin-Reed-Sternberg (HRS) cells of primary diagnostic samples of cHL. Formalin-Fixed Paraffin-Embedded (FFPE) lymph node samples from 88 patients with cHL were analyzed. Patients were treated with the standard first-line chemotherapy (CT) with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) followed by radiotherapy. The Kaplan-Meier method and the Cox proportional hazards model were used for carrying out the survival analysis. In order to investigate whether the influence of EBV was age-dependent, analyses were performed both for patients of all ages and for age-stratified subgroups. In bivariate analysis, the expression of EBV was associated with older age (p = 0.011), mixed cellularity subtype cHL (p < 0.001) and high risk International Prognostic Score (IPS) (p = 0.023). Overall survival (OS) and progression-free survival (PFS) were associated with the presence of bulky disease (p = 0.009) and advanced disease at diagnosis (p = 0.016). EBV-positive cases did not present a significantly lower OS and PFS in comparison with EBV-negative cases, for all ages and when stratifying for age. When adjusted for covariates, absence of bulky disease at diagnosis (HR: 0.102, 95% CI: 0.02-0.48, p = 0.004) and limited disease stages (I-II) (HR: 0.074, 95% CI: 0.01-0.47, p = 0.006) were associated with a significant better OS. For PFS, limited-disease stages also retained prognostic impact in the multivariate Cox regression (HR: 0.145, 95% CI: 0.04-0.57, p = 0.006). These results are of importance as the early identification of prognostic biomarkers in cHL is critical for guiding and personalizing therapeutic decisions. The prognostic role of EBV in cHL could be modulated by the type of CT protocol employed and interact with the rest of presenting features.

Information and Scientific Impact of Advanced Therapies in the Age of Mass Media: Altmetrics-Based Analysis of Tissue Engineering.

BACKGROUND: Tissue engineering (TE) constitutes a multidisciplinary field aiming to construct artificial tissues to regenerate end-stage organs. Its development has taken place since the last decade of the 20th century, entailing a clinical revolution. TE research groups have worked and shared relevant information in the mass media era. Thus, it would be interesting to study the online dimension of TE research and to compare it with traditional measures of scientific impact. OBJECTIVE: The objective of this study was to evaluate the online dimension of TE documents from 2012 to 2018 using metadata obtained from the Web of Science (WoS) and Altmetric and to develop a prediction equation for the impact of TE documents from altmetric scores. METHODS: We analyzed 10,112 TE documents through descriptive and statistical methods. First, the TE temporal evolution was exposed for WoS and 15 online platforms (news, blogs, policy, Twitter, patents, peer review, Weibo, Facebook, Wikipedia, Google, Reddit, F1000, Q&A, video, and Mendeley Readers). The 10 most cited TE original articles were ranked according to the normalized WoS citations and the normalized Altmetric Attention Score. Second, to better comprehend the TE online framework, correlation and factor analyses were performed based on the suitable results previously obtained for the Bartlett sphericity and Kaiser-Meyer-Olkin tests. Finally, the linear regression model was applied to elucidate the relation between academics and online media and to construct a prediction equation for TE from altmetrics data. RESULTS: TE dynamic shows an upward trend in WoS citations, Twitter, Mendeley Readers, and Altmetric Scores. However, WoS and Altmetric rankings for the most cited documents clearly differ. When compared, the best correlation results were obtained for Mendeley Readers and WoS (ρ=0.71). In addition, the factor analysis identified 6 factors that could explain the previously observed differences between academic institutions and the online platforms evaluated. At this point, the mathematical model constructed is able to predict and explain more than 40% of TE WoS citations from Altmetric scores. CONCLUSIONS: Scientific information related to the construction of bioartificial tissues increasingly reaches society through different online media. Because the focus of TE research importantly differs when the academic institutions and online platforms are compared, basic and clinical research groups, academic institutions, and health politicians should make a coordinated effort toward the design and implementation of adequate strategies for information diffusion and population health education.

Translational Applications of Artificial Intelligence and Machine Learning for Diagnostic Pathology in Lymphoid Neoplasms: A Comprehensive and Evolutive Analysis.

Genomic analysis and digitalization of medical records have led to a big data scenario within hematopathology. Artificial intelligence and machine learning tools are increasingly used to integrate clinical, histopathological, and genomic data in lymphoid neoplasms. In this study, we identified global trends, cognitive, and social framework of this field from 1990 to 2020. Metadata were obtained from the Clarivate Analytics Web of Science database in January 2021. A total of 525 documents were assessed by document type, research areas, source titles, organizations, and countries. SciMAT and VOSviewer package were used to perform scientific mapping analysis. Geographical distribution showed the USA and People's Republic of China as the most productive countries, reporting up to 190 (36.19%) of all documents. A third-degree polynomic equation predicts that future global production in this area will be three-fold the current number, near 2031. Thematically, current research is focused on the integration of digital image analysis and genomic sequencing in Non-Hodgkin lymphomas, prediction of chemotherapy response and validation of new prognostic models. These findings can serve pathology departments to depict future clinical and research avenues, but also, public institutions and administrations to promote synergies and optimize funding allocation.

The challenge of discovering the threshold concepts of medical research areas: A bibliometrics-based approach.

During the last XX century, several changes were applied to traditional educational methods, positioning the student as a central actor in the learning process. One of the pedagogical theories developed was the Threshold Concepts (TC) educational framework, based on education as a space of uncertainty, where the student needs to learn a certain concept or learning experiences that allow developing a new way of thinking. In medical education, written accounts about significant learning experiences, analysis of practice essays and semi-structured focus groups interviews have been applied to identify TC. In that way, our hypothesis is that the use of bibliometrics, as a tool to discover hidden relations between keywords, can overcome traditional difficulties related to TC identification. Keywords are applied to highlight the content of a digital object; they are concepts with a special meaning, similar to TC. Our challenge is to identify the bibliometric indexes that are able to show the relationship between the keywords that make them TC, especially in a medical context. In previous scientific literature, several methods were applied, mainly based on qualitative assessment. In this sense, we propose a quantitative, objective, and reproducible approach that can enrich the learning process from a scientific-based perspective.

An Evolutive and Scientometric Research on Tissue Engineering Reviews.

Number of publications has been widely used as a measure of research output, especially academic and university research. Number of publications in tissue engineering (TE) has increased year by year since early 1990s. However, after an exponential growth phase, recently publications increase at lower rates, suggesting a consolidation process in which reviews become a relevant and high-evidence document type. The aim of this study is to perform a scientometric evaluation of published literature reviews on TE to assess the status of scientific evolution and confirm the consolidation of TE as a research area. Published reviews on TE from 1991 to 2018 were retrieved from Web of Science core collection and this corpus of knowledge was analyzed by growth rate, research area, source title, and citation. Our results revealed that TE can be considered a consolidating area as it leaves the forefront stage of a gompertzian growth curve model. Original research/review ratio is lineally decreasing during the past decade. The emergence of reviews serves to confirm and refute hypothesis and build up a more reliable theoretical framework as well as a guide for future educational approaches. Distribution assessment of categories and journals indicates the multidisciplinary profile of this area focused on the design and development of new tissues. Biomedical sciences become relevant productors of reviews as they need to support TE innovations with high evidence leading to a safer and more efficient treatment of current injuries and diseases. Impact statement Scientometric analysis of published reviews about tissue engineering (TE) suggests that TE can be considered a consolidating area as it leaves the forefront stage of a gompertzian growth curve model. Biomedical sciences become relevant productors of reviews as they need to support TE innovations with high evidence leading to a safer and more efficient treatment of current injuries and diseases.

Identification of Cognitive and Social Framework of Tissue Engineering by Science Mapping Analysis.

IMPACT STATEMENT: This study evaluates the cognitive structure and social behavior of tissue engineering (TE) based on a science mapping analysis. Understanding the terms and topics that play a key role in the development of TE can help administrative authorities to better plan funding. Moreover, a better knowledge of collaborative networks in TE and the identification of potential new opportunities for collaboration may enhance synergies in scientific activities to implement future approaches to therapy.

Conceptions of learning factors in postgraduate health sciences master students: a comparative study with non-health science students and between genders.

BACKGROUND: The students' conceptions of learning in postgraduate health science master studies are poorly understood. The aim of this study was to compare the factors influencing conceptions of learning in health sciences and non-health sciences students enrolled in postgraduate master programs in order to obtain information that may be useful for students and for future postgraduate programs. METHODS: A modified version of the Learning Inventory Conception Questionnaire (COLI) was used to compare students' conception learning factors in 131 students at the beginning of their postgraduate studies in health sciences, experimental sciences, arts and humanities and social sciences. RESULTS: The present study demonstrates that a set of factors may influence conception of learning of health sciences postgraduate students, with learning as gaining information, remembering, using, and understanding information, awareness of duty and social commitment being the most relevant. For these students, learning as a personal change, a process not bound by time or place or even as acquisition of professional competences, are less relevant. According to our results, this profile is not affected by gender differences. CONCLUSIONS: Our results show that the overall conceptions of learning differ among students of health sciences and non-health sciences (experimental sciences, arts and humanities and social sciences) master postgraduate programs. These finding are potentially useful to foster the learning process of HS students, because if they are metacognitively aware of their own conception or learning, they will be much better equipped to self-regulate their learning behavior in a postgraduate master program in health sciences.

Global Tissue Engineering Trends: A Scientometric and Evolutive Study.

Tissue engineering (TE) is defined as a multidisciplinary scientific discipline with the main objective to develop artificial bioengineered living tissues to regenerate damaged or lost tissues. Since its appearance in 1988, TE has globally spread to improve current therapeutic approaches, entailing a revolution in clinical practice. The aim of this study is to analyze global research trends on TE publications to realize the scenario of TE research from 1991 to 2016 by using document retrieval from Web of Science database and bibliometric analysis. Document type, language, source title, authorship, countries and filiation centers, and citation count were evaluated in 31,859 documents. Obtained results suggest a great multidisciplinary role of TE due to a wide spectrum-up to 51-of scientific research areas identified in the corpus of literature, being predominant technological disciplines as Material Sciences or Engineering, followed by biological and biomedical areas, as Cell Biology, Biotechnology, or Biochemistry. Distribution of authorship, journals, and countries revealed a clear imbalance, in which a minority is responsible for a majority of documents. Such imbalance is notorious in authorship, where a 0.3% of authors are involved in half of the whole production.