[Trauma Injuries Associated with Rope Bullfights in the Azores: A Cross-Sectional Study]. / Trauma Associado às Touradas à Corda nos Açores: Um Estudo Transversal.

INTRODUCTION: The aim of the study was to describe trauma injuries associated with rope bullfights in the Azores, Portugal, regarding the cause of the incident, trauma mechanism, most affected anatomical areas, and injury severity. METHODS: Two-year cross-sectional study in the local hospital with prospective data collection. Patients who were consecutively admitted to the local hospital's emergency department with trauma injuries from the bull's direct impact or from falls either during the bull's escape or when handling the rope, were included. Data on general demographics, lesion characteristics, treatments, need for hospitalization and mortality were collected. RESULTS: Fifty-six incidents and 80 trauma injuries were identified. The main cause of trauma was the bull's direct impact (37; 66.07%) and the mechanism of injury was blunt trauma in all patients (100%; 56). Head and neck injuries (27; 33.75%) were the most common. The median Injury Severity Score at the emergency department admission was 4. Major trauma was noted in five patients (8.92%). Ten patients (17.85%) needed hospitalization with a median hospital stay of seven days. Three of the 10 hospitalized patients (30%) were previously admitted to the intensive care unit. Surgery was performed in six patients (10.71%). CONCLUSION: The main cause of trauma was the bull's direct impact, and the mechanism of injury was blunt trauma. The most affected anatomical areas were the head and neck. These findings are a wake-up call to the impact of these events regarding the economic costs they entail, the costs for the health of the local population, the safety measures currently implemented and the availability of the necessary means to treat these patients.

Introdução: O objetivo deste estudo foi caracterizar as lesões traumáticas tauromáquicas ocorridas nas touradas à corda nos Açores no que diz respeito à causa do incidente, mecanismo de trauma, área anatómica mais afetada e gravidade das lesões. Métodos: Estudo unicêntrico, transversal, com a colheita prospetiva de dados realizada durante dois anos. Foram incluídos os doentes que consecutivamente recorreram ao serviço de urgência do hospital local por lesões traumáticas ocorridas por trauma direto com o animal ou quedas aquando da fuga ou manuseio da corda. Foram colhidos dados demográficos gerais, características da lesão, tratamentos efetuados, necessidade de internamento hospitalar e mortalidade. Foi realizada uma análise estatística descritiva com recurso ao software estatístico SPSS. Resultados: Registaram-se 56 admissões hospitalares e 80 lesões traumáticas. A principal causa de traumatismo foi o trauma direto com o animal (37; 66,07%) e o mecanismo de lesão foi o trauma fechado (56; 100%). As áreas anatómicas mais afetadas foram a cabeça e pescoço (27; 33,75%). A mediana de Injury Severity Score foi de 4 à admissão hospitalar. Cinco doentes (8,92%) apresentaram trauma major. Dez doentes (17,85%) necessitaram de internamento hospitalar com uma mediana de dias de internamento de sete (IIQ 4,5 dias). Três (30%) dos doentes internados necessitaram de internamento em unidade de cuidados intensivos. Seis doentes (10,71%) foram submetidos a cirurgia. Conclusão: A principal causa de traumatismo foi o trauma direto com o animal e o mecanismo de lesão foi o trauma fechado. As áreas anatómicas mais afetadas foram a cabeça e pescoço. Estes dados constituem um alerta para o impacto destes eventos no que diz respeito aos custos económicos que acarretam, aos custos para a saúde da população local, às medidas de segurança atualmente implementadas e à disponibilidade dos meios necessários para tratar estes doentes.

A Comparison of Cell-Cell Interaction Prediction Tools Based on scRNA-seq Data.

Computational prediction of cell-cell interactions (CCIs) is becoming increasingly important for understanding disease development and progression. We present a benchmark study of available CCI prediction tools based on single-cell RNA sequencing (scRNA-seq) data. By comparing prediction outputs with a manually curated gold standard for idiopathic pulmonary fibrosis (IPF), we evaluated prediction performance and processing time of several CCI prediction tools, including CCInx, CellChat, CellPhoneDB, iTALK, NATMI, scMLnet, SingleCellSignalR, and an ensemble of tools. According to our results, CellPhoneDB and NATMI are the best performer CCI prediction tools, among the ones analyzed, when we define a CCI as a source-target-ligand-receptor tetrad. In addition, we recommend specific tools according to different types of research projects and discuss the possible future paths in the field.

VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway.

Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.

Chatbots and messaging platforms in the classroom: An analysis from the teacher's perspective.

Messaging platforms are applications, generally mediated by an app, desktop program or the web, mainly used for synchronous communication among users. As such, they have been widely adopted officially by higher education establishments, after little or no study of their impact and perception by the teachers. We think that the introduction of these new tools and the opportunities and challenges they have needs to be studied carefully in order to adopt the model, as well as the tool, that is the most adequate for all parties involved. We already studied the perception of these tools by students, in this paper we examine the teachers' experiences and perceptions through a survey that we validated with peers, and what they think these tools should make or serve so that it enhances students learning and helps them achieve their learning objectives. The survey has been distributed among tertiary education teachers, both in universitary and other kind of tertiary establishments, based in Spain (mainly) and Spanish-speaking countries. We have focused on collecting teachers' preferences and opinions on the introduction of messaging platforms in their day-to-day work, as well as other services attached to them, such as chatbots. What we intend with this survey is to understand their needs and to gather information about the various educational use cases where these tools could be valuable. In addition, an analysis of how and when teachers' opinions towards the use of these tools varies across gender, experience, and their discipline of specialization is presented. The key findings of this study highlight the factors that can contribute to the advancement of the adoption of messaging platforms and chatbots in higher education institutions to achieve the desired learning outcomes.

Epidemiological study of vaccination against SARS-CoV-2 and its impact on COVID-19 progression in a cohort of patients in gran Canaria.

Objectives. We analyzed the impact of age, sex, vaccination against COVID-19, immunosuppressive treatment, and comorbidities on patients' risk of requiring hospital admission or of death. Methods. Population-based observational retrospective study conducted on a cohort of 19,850 patients aged 12 years or more, who were diagnosed with COVID-19 between June 1st and December 31st, 2021, in the island of Gran Canaria. Results. Hypertension (18.5%), asthma (12.8%) and diabetes (7.2%) were the most frequent comorbidities; 147 patients died (0.7%). The combination of advanced age, male sex, cancer, coronary heart disease, immunosuppressive treatment, hospital admission, admission to the intensive care unit, mechanical ventilation and lack of complete COVID-19 vaccination or booster dose was strongly predictive of mortality (p < 0.05); 831 patients required hospital admission and it was more frequent in men, older age groups, and patients with cancer, diabetes, arterial hypertension, chronic obstructive pulmonary disease, congestive heart failure or immunosuppressive treatment. The COVID-19 vaccine booster dose was associated with a lower risk of death ([OR] 0.11, 95% CI 0.06-0.21, p < 0.05) or hospital admission ([OR] 0.36, 95% CI 0.29-0.46, p < 0.05). Conclusions. Cancer, coronary heart disease, and immunosuppressive treatment were associated with increased COVID-19 mortality. More complete vaccination was associated with lower risk of hospital admission or death. Three doses of the SARS-CoV-2 vaccine were highly associated with the prevention of death and hospital admission in all age groups. These findings suggest that COVID-19 vaccination can help bring the pandemic under control.

Objetivos. Analizamos el impacto de la edad, el sexo, la vacunación frente a la COVID-19, el tratamiento inmunosupresor y las comorbilidades en el riesgo de los pacientes de precisar ingreso hospitalario o de fallecer.Métodos. Estudio retrospectivo observacional de base poblacional realizado sobre una cohorte de 19.850 pacientes de 12 años o más, que fueron diagnosticados de COVID-19 entre el 1 de junio y el 31 de diciembre de 2021, en la isla de Gran Canaria.Resultados. La hipertensión arterial (18,5%), el asma (12,8%) y la diabetes (7,2%) fueron las comorbilidades más frecuentes; Fallecieron 147 pacientes (0,7%). La combinación de edad avanzada, sexo masculino, cáncer, cardiopatía coronaria, tratamiento inmunosupresor, ingreso hospitalario, ingreso en unidad de cuidados intensivos, ventilación mecánica y la falta de vacunación completa contra el COVID-19 o dosis de refuerzo fue fuertemente predictiva de mortalidad (p < 0,05); 831 pacientes requirieron ingreso hospitalario y fue más frecuente en hombres, grupos de mayor edad y pacientes con cáncer, diabetes, hipertensión arterial, enfermedad pulmonar obstructiva crónica, insuficiencia cardiaca congestiva o tratamiento inmunosupresor. La dosis de refuerzo contra la vacuna del COVID-19 se asoció con un menor riesgo de muerte ([OR] 0.11, IC 95% 0.06­0.21, p < 0,05) o ingreso hospitalario ([OR] 0.36, IC 95% 0.29­0.46; p < 0,05).Conclusiones. El cáncer, la enfermedad coronaria y el tratamiento inmunosupresor se asociaron con una mayor mortalidad por COVID-19. Una vacunación más completa se asoció con un menor riesgo de hospitalización o muerte. Tres dosis de la vacuna contra el SARS-CoV-2 se asociaron a una mayor prevención de la muerte y el ingreso hospitalario relacionados con la COVID-19 en todos los grupos de edad. Estos hallazgos sugieren que la vacunación contra el COVID-19 puede ayudar a controlar la pandemia.

PDGF-D-induced immunoproteasome activation and cell-cell interactions.

Platelet-derived growth factor-D (PDGF-D) is abundantly expressed in ocular diseases. Yet, it remains unknown whether and how PDGF-D affects ocular cells or cell-cell interactions in the eye. In this study, using single-cell RNA sequencing (scRNA-seq) and a mouse model of PDGF-D overexpression in retinal pigment epithelial (RPE) cells, we found that PDGF-D overexpression markedly upregulated the key immunoproteasome genes, leading to increased antigen processing/presentation capacity of RPE cells. Also, more than 6.5-fold ligand-receptor pairs were found in the PDGF-D overexpressing RPE-choroid tissues, suggesting markedly increased cell-cell interactions. Moreover, in the PDGF-D-overexpressing tissues, a unique cell population with a transcriptomic profile of both stromal cells and antigen-presenting RPE cells was detected, suggesting PDGF-D-induced epithelial-mesenchymal transition of RPE cells. Importantly, administration of ONX-0914, an immunoproteasome inhibitor, suppressed choroidal neovascularization (CNV) in a mouse CNV model in vivo. Together, we show that overexpression of PDGF-D increased pro-angiogenic immunoproteasome activities, and inhibiting immunoproteasome pathway may have therapeutic value for the treatment of neovascular diseases.

Estudio epidemiológico sobre el impacto de la vacunación antigripal en la evolución clínica de pacientes con COVID-19 y la coinfección por ambos virus en Gran Canaria, España / Epidemiological study on the impact of influenza vaccination on the clinical course of patients with COVID-19 and co-infection by both viruses in Gran Canaria, Spain

Objetivo: Analizar la frecuencia de coinfecciones entre los virus gripales y el SARS-CoV-2, además de las diferencias en la evolución (riesgo de mortalidad, ingreso hospitalario o en intensivos) de los pacientes infectados por el virus del SARS-CoV-2 según vacunación o no vacunación de la gripe en la temporada 2021-2022. Método: Estudio retrospectivo observacional de base poblacional en una cohorte de 19.850 pacientes diagnosticados de COVID-19 entre el 1 de junio de 2021 y 28 de febrero de 2022 en la isla de Gran Canaria. Resultados. Fueron vacunados de la gripe 1.789 personas, el 9% del total de pacientes diagnosticados de COVID-19. 13.676 personas (68,9%) contaban con pauta completa de vacunación del COVID-19. En el periodo comprendido entre el 1 de junio de 2021 y 28 de febrero de 2022 se registraron 8 casos de coinfección gripe y COVID-19. Hipertensión (18,5%), asma (12,8%) y diabetes (7,2%) fueron las comorbilidades más frecuentes. Hubo 147 defunciones (0,7%). Las personas de mayor edad ([OR] 1,11 IC 95% 1,09-1,13) y con cáncer ([OR] 4,21 IC 95% 2,58-6,89) tuvieron mayor riesgo de fallecer por COVID-19 (p<0,05). El sexo femenino fue considerado un factor protector ([OR] 0,61 IC 95% 0,40-0,92). Conclusiones: La edad avanzada, el sexo masculino y el cáncer fueron factores pronósticos independientes de mortalidad. Tres dosis de la vacuna del SARS-CoV-2 y la vacuna de la gripe fueron altamente efectivas para prevenir muertes e ingresos relacionados con COVID-19. Estos hallazgos sugieren que la vacunación contra la gripe puede ayudar a controlar la pandemia. (AU)

Objectives: To analyze the frequency of influenza and SARS-CoV-2 co-infections, as well as the differences in the course of disease (risk of mortality, hospital and intensive care admissions) in patients infected with the SARS-CoV-2 virus in relation to flu vaccination status in the 2021-2022 season.Methodology. Population-based observational retrospective study in a cohort of 19,850 patients diagnosed with COVID-19 between June 1, 2021 and February 28, 2022 on the island of Gran Canaria. Results: A total of 1,789 patients (9%) diagnosed with COVID-19 had received flu vaccinations. 13,676 people (68.9%) had a full course of COVID-19 vaccinations. In the period between June 1, 2021 and February 28, 2022, 8 cases of flu and COVID-19 coinfection were recorded. Hypertension (18.5%), asthma (12.8%) and diabetes (7.2%) were the most frequent comorbidities. There were 147 deaths (0.7%). Older patients ([OR] 1.11 95% CI 1.09-1.13) and people with cancer ([OR] 4.21 95% CI 2.58-6.89) had a higher risk of dying from COVID-19 (p<0.05). Female sex was noted as a protective factor ([OR] 0.61 95% CI 0.40-0.92). Conclusions: Old age, male sex and cancer were independent prognostic factors for mortality. Three doses of SARS-CoV-2 vaccines and influenza vaccines were highly effective in preventing COVID-19-related deaths and hospital admissions. These findings suggest that flu vaccination can help control the pandemic. (AU)

Nursing Diagnoses, Planned Outcomes and Associated Interventions with Highly Complex Chronic Patients in Primary Care Settings: An Observational Study.

The information logged by nurses on electronic health records (EHRs) using standardised nursing languages can help us identify the characteristics of highly complex chronic patients (HCCP) by focusing on care in terms of patients' health needs. The aim of this study was to describe the profile of HCCPs using EHRs from primary care (PC) facilities, presenting patients' characteristics, functional status based on health patterns, NANDA-I nursing diagnoses, health goals based on Nursing Outcomes Classification (NOC), and care interventions using Nursing Interventions Classification (NIC). With an observational, descriptive, cross-sectional, epidemiological study design, this study was carried out with a sample of 51,374 individuals. The variables were grouped into sociodemographic variables, clinical variables, resources, functional status (health patterns), nursing diagnoses, outcomes, and interventions. A total of 57.4% of the participants were women, with a mean age of 73.3 (12.2), and 51% were frail or dependent. Prevalent conditions included high blood pressure (87.2%), hyperlipidaemia (80%), osteoarthritis (67.8%), and diabetes (56.1%). The participants were frequent users of healthcare services, with 12.1% admitted to hospital in the past year. Some 49.2% had one to four health patterns assessed, with more information on biological and functional aspects than on psychosocial aspects. The mean number of nursing diagnoses was 7.3 (5.2), NOC outcomes 5.1 (4.1), and NIC interventions 8.1 (6.9). Moderately and highly significant differences were observed between dysfunction in physical activity/exercise health pattern and age group, and between dysfunction in other health patterns and classification as a frail or dependent elderly person. Regarding the presence of certain nursing diagnoses, significant differences were observed by age group, classification of elderly person status, and presence of diseases. A total of 20 NIC interventions showed moderately or relatively strong associations for older age groups, higher levels of dependency, and chronic health conditions.

Situation of the Elderly Living Alone: Morbidity and Services Provided from the Field of Primary Health Care of Gran Canaria.

The elderly suffer a greater number of health problems and have greater need for assistance and care. (1) Background: to determine the profile of the elderly who live alone, identified according to the Primary Care Health Record of Gran Canaria, and to analyze the sociodemographic data of the target population and determine the characteristics related to morbidity. (2) Methods: descriptive, prospective, cross-sectional study carried out in the Primary Health Care Management of Gran Canaria. The study population was all adults over 65 years of age living alone. The instrument used was the Drago-Electronic Health Record. Data analysis was carried out using RStudio version 1.1.447 software, and descriptive analysis and inferential analysis were carried out using the Chi-square values, T-test for independent samples, and ANOVA. (3) Results: The sample amounted to 8679 subjects, predominantly female sex (86.14%) and with a mean age of 79.4 years. Of the sample, 6.4% lived alone. Based on the classification by Adjusted Morbidity Groups (AMG), subjects with "moderate complications" predominated at 45.5%. (4) Conclusions: It is necessary to implement this type of stratification tool, which allows interventions to be carried out in elderly people at risk.

GSA Central-A web platform to perform, learn, and discuss gene set analysis.

Gene Set Analysis (GSA) is one of the most commonly used strategies to analyze omics data. Hundreds of GSA-related papers have been published, giving birth to a GSA field in Bioinformatics studies. However, as the field grows, it is becoming more difficult to obtain a clear view of all available methods, resources, and their quality. In this paper, we introduce a web platform called "GSA Central" which, as its name indicates, acts as a focal point to centralize GSA information and tools useful to beginners, average users, and experts in the GSA field. "GSA Central" contains five different resources: A Galaxy instance containing GSA tools ("Galaxy-GSA"), a portal to educational material ("GSA Classroom"), a comprehensive database of articles ("GSARefDB"), a set of benchmarking tools ("GSA BenchmarKING"), and a blog ("GSA Blog"). We expect that "GSA Central" will become a useful resource for users looking for introductory learning, state-of-the-art updates, method/tool selection guidelines and insights, tool usage, tool integration under a Galaxy environment, tool design, and tool validation/benchmarking. Moreover, we expect this kind of platform to become an example of a "thematic platform" containing all the resources that people in the field might need, an approach that could be extended to other bioinformatics topics or scientific fields.

Chromatin Hubs: A biological and computational outlook.

This review discusses our current understanding of chromatin biology and bioinformatics under the unifying concept of "chromatin hubs." The first part reviews the biology of chromatin hubs, including chromatin-chromatin interaction hubs, chromatin hubs at the nuclear periphery, hubs around macromolecules such as RNA polymerase or lncRNAs, and hubs around nuclear bodies such as the nucleolus or nuclear speckles. The second part reviews existing computational methods, including enhancer-promoter interaction prediction, network analysis, chromatin domain callers, transcription factory predictors, and multi-way interaction analysis. We introduce an integrated model that makes sense of the existing evidence. Understanding chromatin hubs may allow us (i) to explain long-unsolved biological questions such as interaction specificity and redundancy of mechanisms, (ii) to develop more realistic kinetic and functional predictions, and (iii) to explain the etiology of genomic disease.

Assessment of SARS-CoV-2 Infection According to Previous Metabolic Status and Its Association with Mortality and Post-Acute COVID-19.

Background. SARS-CoV-2 infection was analyzed according to previous metabolic status and its association with mortality and post-acute COVID-19. Methods. A population-based observational retrospective study was conducted on a cohort of 110,726 patients aged 12 years or more who were diagnosed with COVID-19 infection between June 1st, 2021, and 28 February 2022 on the island of Gran Canaria, Spain. Results. In the 347 patients who died, the combination of advanced age, male sex, cancer, immunosuppressive therapy, coronary heart disease, elevated total cholesterol and reduced high-density lipoprotein cholesterol (HDL-C) was strongly predictive of mortality (p < 0.05). In the 555 patients who developed post-acute COVID-19, the persistence of symptoms was most frequent in women, older subjects and patients with obstructive sleep apnea syndrome, asthma, elevated fasting glucose levels or elevated total cholesterol (p < 0.05). A complete vaccination schedule was associated with lower mortality (incidence rate ratio (IRR) 0.5, 95%CI 0.39−0.64; p < 0.05) and post-acute COVID-19 (IRR 0.37, 95%CI 0.31−0.44; p < 0.05). Conclusions. Elevated HDL-C and elevated total cholesterol were significantly associated with COVID-19 mortality. Elevated fasting glucose levels and elevated total cholesterol were risk factors for the development of post-acute COVID-19.

PDGFD switches on stem cell endothelial commitment.

The critical factors regulating stem cell endothelial commitment and renewal remain not well understood. Here, using loss- and gain-of-function assays together with bioinformatic analysis and multiple model systems, we show that PDGFD is an essential factor that switches on endothelial commitment of embryonic stem cells (ESCs). PDGFD genetic deletion or knockdown inhibits ESC differentiation into EC lineage and increases ESC self-renewal, and PDGFD overexpression activates ESC differentiation towards ECs. RNA sequencing reveals a critical requirement of PDGFD for the expression of vascular-differentiation related genes in ESCs. Importantly, PDGFD genetic deletion or knockdown increases ESC self-renewal and decreases blood vessel densities in both embryonic and neonatal mice and in teratomas. Mechanistically, we reveal that PDGFD fulfills this function via the MAPK/ERK pathway. Our findings provide new insight of PDGFD as a novel regulator of ESC fate determination, and suggest therapeutic implications of modulating PDGFD activity in stem cell therapy.

Care Needs of Highly Complex Chronic Patients in the Canary Islands: An Observational Study.

In the last few decades, the impact of chronic health conditions on health systems, as well as on the quality of life, frailty, and dependence of those affected, has been brought to light. The objective of this study was to describe the population care needs of highly complex chronic patients (HCCPs). METHODS: An epidemiological observational study was conducted. RESULTS: A total of 13,262 patients were identified, 51% of which were elderly women. Among all patients, 84.4% had received a nursing assessment related to health patterns. Three diagnoses were established in 25% of the sample: readiness for enhanced health management, impaired skin integrity, and risk for falls. There were significant differences according to age, most importantly in terms of impaired skin integrity (39% of patients under 80 years old). Risk for falls, social isolation, situational low self-esteem, chronic low self-esteem, impaired home maintenance, anxiety, ineffective health management, ineffective coping, impaired memory, insomnia, and self-care deficits were more common in those living alone. A total of 37 diagnoses featured differences according to frailty/dependence. Approximately 23% of HCCPs suffered from frail elderly syndrome. CONCLUSIONS: This study presents the most common care needs of HCCPs, describing the sociodemographic profile of this part of the population. The planning of HCCP care varies in nature. Factors such as the dependence level and frailty of these people should be taken into consideration.

Automatic cell type identification methods for single-cell RNA sequencing.

Single-cell RNA sequencing (scRNA-seq) has become a powerful tool for scientists of many research disciplines due to its ability to elucidate the heterogeneous and complex cell-type compositions of different tissues and cell populations. Traditional cell-type identification methods for scRNA-seq data analysis are time-consuming and knowledge-dependent for manual annotation. By contrast, automatic cell-type identification methods may have the advantages of being fast, accurate, and more user friendly. Here, we discuss and evaluate thirty-two published automatic methods for scRNA-seq data analysis in terms of their prediction accuracy, F1-score, unlabeling rate and running time. We highlight the advantages and disadvantages of these methods and provide recommendations of method choice depending on the available information. The challenges and future applications of these automatic methods are further discussed. In addition, we provide a free scRNA-seq data analysis package encompassing the discussed automatic methods to help the easy usage of them in real-world applications.

Popularity and performance of bioinformatics software: the case of gene set analysis.

BACKGROUND: Gene Set Analysis (GSA) is arguably the method of choice for the functional interpretation of omics results. The following paper explores the popularity and the performance of all the GSA methodologies and software published during the 20 years since its inception. "Popularity" is estimated according to each paper's citation counts, while "performance" is based on a comprehensive evaluation of the validation strategies used by papers in the field, as well as the consolidated results from the existing benchmark studies. RESULTS: Regarding popularity, data is collected into an online open database ("GSARefDB") which allows browsing bibliographic and method-descriptive information from 503 GSA paper references; regarding performance, we introduce a repository of jupyter workflows and shiny apps for automated benchmarking of GSA methods ("GSA-BenchmarKING"). After comparing popularity versus performance, results show discrepancies between the most popular and the best performing GSA methods. CONCLUSIONS: The above-mentioned results call our attention towards the nature of the tool selection procedures followed by researchers and raise doubts regarding the quality of the functional interpretation of biological datasets in current biomedical studies. Suggestions for the future of the functional interpretation field are made, including strategies for education and discussion of GSA tools, better validation and benchmarking practices, reproducibility, and functional re-analysis of previously reported data.

Up to half of patients diagnosed with chronic lymphocytic leukemia in México may not require treatment.

Introduction: Although therapeutic choices for patients with chronic lymphocytic leukemia (CLL) were once limited, treatment of this disease has vastly improved in the last decades.Patients and methods: Consecutive CLL patients diagnosed in a single institution were analyzed. Treatment was withheld in persons with CLL Rai stage 0 or 1, until progression and in persons with stages 2-4, with a negative expression of ZAP-70 until progression. Between 1983 and 1991, patients were give chlorambucil and prednisone (CP); after 1991 fludarabine and cyclophosphamide (FC) and after 1998, rituximab and FC (FCR).Results: 98 patients with CLL were identified; 49 were followed for >3 months. 21 persons (43%) did not require treatment nor progressed; 14 received CP, 6 FC, 7 FCR and one rituximab. Median overall survival (OS) has not been reached, being above 247 months; median OS for patients given CP was 115 months, for FC above 132 months and for FCR above 136 months (p > 0.5).Conclusion: CLL seems to be less aggressive in Mexican mestizos than in Caucasians; 43% of patients do not need treatment at all.

GREG-studying transcriptional regulation using integrative graph databases.

A gene regulatory process is the result of the concerted action of transcription factors, co-factors, regulatory non-coding RNAs (ncRNAs) and chromatin interactions. Therefore, the combination of protein-DNA, protein-protein, ncRNA-DNA, ncRNA-protein and DNA-DNA data in a single graph database offers new possibilities regarding generation of biological hypotheses. GREG (The Gene Regulation Graph Database) is an integrative database and web resource that allows the user to visualize and explore the network of all above-mentioned interactions for a query transcription factor, long non-coding RNA, genomic range or DNA annotation, as well as extracting node and interaction information, identifying connected nodes and performing advanced graphical queries directly on the regulatory network, in a simple and efficient way. In this article, we introduce GREG together with some application examples (including exploratory research of Nanog's regulatory landscape and the etiology of chronic obstructive pulmonary disease), which we use as a demonstration of the advantages of using graph databases in biomedical research. Database URL: https://mora-lab.github.io/projects/greg.html, www.moralab.science/GREG/.

Treatment of Persons with Multiple Myeloma in Underprivileged Circumstances: Real-World Data from a Single Institution.

BACKGROUND: The treatment of patients with multiple myeloma (MM) has evolved in recent years, and the disease-associated prognosis has improved substantially. This improvement has been driven largely by the approval of novel agents, many of which are expensive and not universally available. Less expensive but effective approaches would be of value globally. PATIENTS AND METHODS: All consecutive MM patients diagnosed in the Centro de Hematología y Medicina Interna de Puebla after 1993 were included in this study. Patients were given oral thalidomide (100 mg/day), oral dexamethasone (36-40 mg/week), and aspirin 100 mg/day. Bor-tezomib (1.75 mg s.c. every week) was administered to those who could afford it. After 4-6 weeks of treatment, patients were offered an outpatient-based hematopoietic cell transplant (HCT). After the recovery of granulocytes following HCT, patients continued indefinitely on thalidomide; those who failed to tolerate thalidomide were switched to lenalidomide (25 mg/day). RESULTS: The median overall survival (OS) for all patients has not been reached and is >157 months. Median follow-up of the patients lasted 14 months (range 1.3-157). The median OS of patients with and without HCT was similar. The response rate (complete remission or very good partial remission) was 72% for those given thalidomide plus dexamethasone versus 88% for those given bortezomib, thalidomide, and dexamethasone before HCT, but OS was not different. As post-HCT maintenance, 37 patients received thalidomide; 26 of those (70%) could be maintained indefinitely on thalidomide, whereas 11 were switched to lenalidomide after a median of 7 months; median OS of patients maintained on thalidomide or lenalidomide after HCT was not different. CONCLUSION: In this series, a regimen incorporating low-cost novel agents and outpatient HCT was associated with excellent long-term survival in the treatment of MM patients. This approach may be a model for MM treatment in underprivileged circumstances.

Gene set analysis methods for the functional interpretation of non-mRNA data-Genomic range and ncRNA data.

Gene set analysis (GSA) is one of the methods of choice for analyzing the results of current omics studies; however, it has been mainly developed to analyze mRNA (microarray, RNA-Seq) data. The following review includes an update regarding general methods and resources for GSA and then emphasizes GSA methods and tools for non-mRNA omics datasets, specifically genomic range data (ChIP-Seq, SNP and methylation) and ncRNA data (miRNAs, lncRNAs and others). In the end, the state of the GSA field for non-mRNA datasets is discussed, and some current challenges and trends are highlighted, especially the use of network approaches to face complexity issues.