A novel representation of genomic sequences for taxonomic clustering and visualization by means of self-organizing maps.

MOTIVATION: Self-organizing maps (SOMs) are readily available bioinformatics methods for clustering and visualizing high-dimensional data, provided that such biological information is previously transformed to fixed-size, metric-based vectors. To increase the usefulness of SOM-based approaches for the analysis of genomic sequence data, novel representation methods are required that automatically and objectively transform aligned nucleotide sequences into numeric vectors, dealing with both nucleotide ambiguity and gaps derived from sequence alignment. RESULTS: Six different codification variants based on Euclidean space, just like SOM processing, have been tested using two SOM models: the classical Kohonen's SOM and growing cell structures. They have been applied to two different sets of sequences: 32 sequences of small sub-unit ribosomal RNA from organisms belonging to the three domains of life, and 44 sequences of the reverse transcriptase region of the pol gene of human immunodeficiency virus type 1 belonging to different groups and sub-types. Our results show that the most important factor affecting the accuracy of sequence clustering is the assignment of an extra weight to the presence of alignment-derived gaps. Although each of the codification variants shows a different level of taxonomic consistency, the results are in agreement with sequence-based phylogenetic reconstructions and anticipate a broad applicability of this codification method.

Inflammatory, procoagulant markers and HIV residual viremia in patients receiving protease inhibitor monotherapy or triple drug therapy: a cross-sectional study.

BACKGROUND: Protease inhibitor monotherapy is associated with more frequent episodes of viral rebounds above 50 copies/mL than triple therapy. OBJECTIVE: To evaluate if, compared to triple-drug therapy, protease inhibitor monotherapy is associated with increased levels of inflammatory/procoagulant markers and more frequent plasma residual viremia detection. METHODS: In this cross-sectional study, we included patients treated for ≥ 1 year with darunavir/ritonavir or lopinavir/ritonavir as monotherapy (n=72) or with two nucleos(t)ides (n=74). All samples were tested for CRP, IL-6, fibrinogen and D-dimer. Residual viremia was determined using an ultrasensitive qualitative nested-PCR of the HIV pol gene with a limit of detection of 1 copy of HIV-RNA. RESULTS: We found no differences in levels of inflammatory/procoagulant markers or in the proportion of patients with plasma residual viremia detection by treatment group. CONCLUSION: The long-term treatment with protease inhibitor monotherapy in the setting of routine clinical practice is not associated with a higher prevalence of plasma residual viremia or more elevated inflammatory/procoagulant markers levels than triple drug therapy.

Catheter directed therapy in high-risk pulmonary embolism: Analysis of 9 cases. / Terapia dirigida por catéter en embolia pulmonar de alto riesgo: análisis de 9 casos.

BACKGROUND: Mechanical thrombectomy is a useful technique in patients with high-risk pulmonary embolism. It is indicated as an alternative to systemic fibrinolysis when it is contraindicated or as an adjuvant therapy when it fails. OBJECTIVE: To describe clinical characteristics, evolution and survival of patients with high-risk pulmonary embolism who have undergone mechanical thrombectomy. METHOD: Single-center retrospective descriptive study of consecutive patients who underwent mechanical thrombectomy. Demographic, clinical and survival variables were analyzed. RESULTS: 9 patients were included (56% men, 44% women). All patients had pulmonary artery pressure assessed using a Swan-Ganz catheter before thrombectomy. The median pulmonary artery pressure before the procedure was 46mmHg (51-38mmHg). Systemic fibrinolysis was also performed in 5 cases, in 2 of them in the setting of cardiorespiratory arrest, without hemorrhagic complications. No patient died during hospitalization. Survival one month after the procedure was 100%. CONCLUSIONS: In our series, mechanical thrombectomy is a useful technique as an alternative to systemic fibrinolysis or as an adjuvant therapy to it.

Cholinergic neurodegeneration and cholesterol metabolism dysregulation by constitutive p75NTR signaling in the p75exonIII-KO mice.

Degeneration of basal forebrain cholinergic neurons (BFCNs) is a hallmark of Alzheimer's disease (AD). However, few mouse models of AD recapitulate the neurodegeneration of the cholinergic system. The p75 neurotrophin receptor, p75NTR, has been associated with the degeneration of BFCNs in AD. The senescence-accelerated mouse prone number 8 (SAMP8) is a well-accepted model of accelerated and pathological aging. To gain a better understanding of the role of p75NTR in the basal forebrain during aging, we generated a new mouse line, the SAMP8-p75exonIII-/-. Deletion of p75NTR in the SAMP8 background induces an increase in the number of BFCNs at birth, followed by a rapid decline during aging compared to the C57/BL6 background. This decrease in the number of BFCNs correlates with a worsening in the Y-maze memory test at 6 months in the SAMP8-p75exonIII-/-. We found that SAMP8-p75exonIII-/- and C57/BL6-p75exonIII-/- mice expressed constitutively a short isoform of p75NTR that correlates with an upregulation of the protein levels of SREBP2 and its targets, HMGCR and LDLR, in the BF of both SAMP8-p75exonIII-/- and C57/BL6-p75exonIII-/- mice. As the neurodegeneration of the cholinergic system and the dysregulation of cholesterol metabolism are implicated in AD, we postulate that the generated SAMP8-p75exonIII-/- mouse strain might constitute a good model to study long-term cholinergic neurodegeneration in the CNS. In addition, our results support the role of p75NTR signaling in cholesterol biosynthesis regulation.

Charged lithium adsorption on pristine and defective silicene: a theoretical study.

We investigated by first principle calculations the adsorption of Liq(q= -1, 0 or +1) on a silicene single layer. Pristine and three different defective silicene configurations with and without Li doping were studied: single vacancy (SV), double vacancy (DV) and Stone-Wales (STW). Structural studies and the adsorption energies of various sites were obtained and compared in order to understand the stability of the Li on the surface. Moreover, electronic structure and charge density difference analysis were performed before and after adsorption at the most stables sites, which showed the presence of a magnetic moment in the undoped SV system, the displacement of the Fermi level produced by Li doping and a charge transfer from Li to the surface. Additionally, quantum capacity (QC) and charge density studies were performed on these systems. This analysis showed that the generation of defects and doping improves the QC of silicene in positive bias, because of the existence of 3p orbital in the zone of the defect. Consequently, the innovative calculations performed in this work of charged lithium doping on silicene can be used for future comparison with experimental studies of this Li-ion battery anode material candidate.

Rapid maxillary expansion versus watchful waiting in pediatric OSA: A systematic review.

Spontaneous resolution of pediatric obstructive sleep apnea (OSA) may stand behind the observed benefit of rapid maxillary expansion (RME), mainly supported by uncontrolled case series. We aimed to review the controlled, ideally randomized, evidence on the effectiveness of RME as compared to watchful waiting or alternative treatment of pediatric OSA. We only found one randomized clinical trial comparing RME with watchful waiting. The other four studies compared RME with the gold-standard treatment adenotonsillectomy, three of them in a non-randomized fashion. The results of the RCT showed no statistically significant differences in the enhancement of main (apnea hypopnea index, AHI) and secondary outcomes between RME and watchful waiting. Furthermore, reproducibility of the published studies was limited by insufficient description of their patients' inclusion criteria. We could not find convincing evidence of the benefit of RME over watchful waiting in patients with pediatric OSA. RCTs with reproducible inclusion criteria comparing RME with watchful waiting are still critically needed to support this intervention for the treatment of pediatric OSA. In the absence of solid evidence with RCT, RME should not be recommended for the treatment of pediatric OSA. PROSPERO REGISTRATION NUMBER: CRD42021249261. RUNNING SUMMARY: This systematic review explores the benefits of rapid maxillary expansion compared to spontaneous resolution of pediatric obstructive sleep apnea.

DatAC: A visual analytics platform to explore climate and air quality indicators associated with the COVID-19 pandemic in Spain.

The coronavirus disease 2019 (COVID-19) pandemic has caused an unprecedented global health crisis, with several countries imposing lockdowns to control the coronavirus spread. Important research efforts are focused on evaluating the association of environmental factors with the survival and spread of the virus and different works have been published, with contradictory results in some cases. Data with spatial and temporal information is a key factor to get reliable results and, although there are some data repositories for monitoring the disease both globally and locally, an application that integrates and aggregates data from meteorological and air quality variables with COVID-19 information has not been described so far to the best of our knowledge. Here, we present DatAC (Data Against COVID-19), a data fusion project with an interactive web frontend that integrates COVID-19 and environmental data in Spain. DatAC is provided with powerful data analysis and statistical capabilities that allow users to explore and analyze individual trends and associations among the provided data. Using the application, we have evaluated the impact of the Spanish lockdown on the air quality, observing that NO2, CO, PM2.5, PM10 and SO2 levels decreased drastically in the entire territory, while O3 levels increased. We observed similar trends in urban and rural areas, although the impact has been more important in the former. Moreover, the application allowed us to analyze correlations among climate factors, such as ambient temperature, and the incidence of COVID-19 in Spain. Our results indicate that temperature is not the driving factor and without effective control actions, outbreaks will appear and warm weather will not substantially limit the growth of the pandemic. DatAC is available at https://covid19.genyo.es.

Randomized Trial Evaluating the Neurotoxicity of Dolutegravir/Abacavir/Lamivudine and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: GESIDA 9016.

BACKGROUND: Despite evidence shown of dolutegravir (DTG)-related neurotoxicity, which may be more common when combined with abacavir (ABC), its reversibility has not been explored in a clinical trial. METHODS: We conducted a randomized, multicenter, open-label, pilot trial to evaluate the reversibility of patient-reported neuropsychiatric symptoms, developed or worsened on DTG/ABC/lamivudine (DTG/ABC/3TC), in virologically suppressed patients switched to cobicistat-boosted-elvitegravir/emtricitabine/tenofovir-alafenamide (EVG/COBI/FTC/TAF). Participants were randomized to immediate switch (baseline) or to defer switch (week 4), and then all completed 24 weeks of follow up on EVG/COBI/FTC/TAF. At each visit, participants completed Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression (HAD) scales and were interviewed about 11 neuropsychiatric symptoms potentially related with DTG through a questionnaire. At baseline and at the end of follow up, they also performed neurocognitive testing. Our primary objective was to compare changes in neuropsychiatric symptoms and PSQI and HAD scales between arms at week 4. Secondary objectives were to evaluate changes in neuropsychiatric symptoms and PSQI and HAD scales at weeks 4, 12, and 24 after switching to EVG/COBI/FTC/TAF and in neurocognitive performance and magnetic resonance imaging biomarkers at end of follow up. RESULTS: Thirty-eight participants were included. Study arms were similar at baseline. At week 4, neuropsychiatric symptoms and PSQI and HAD scores remained unchanged in participants receiving DTG/ABC/3TC and improved significantly in participants receiving EVG/COBI/FTC/TAF. These significant improvements were also observed at weeks 4, 12, and 24 after all participants switched to EVG/COBI/FTC/TAF. In addition, global neurocognitive performance improved (NPZ-7) after switching to EVG/COBI/FTC/TAF. CONCLUSIONS: Neuropsychiatric symptoms in patients on DTG/ABC/3TC could resolve or improve after switching to EVG/COBI/FTC/TAF.

Steady state particle swarm.

This paper investigates the performance and scalability of a new update strategy for the particle swarm optimization (PSO) algorithm. The strategy is inspired by the Bak-Sneppen model of co-evolution between interacting species, which is basically a network of fitness values (representing species) that change over time according to a simple rule: the least fit species and its neighbors are iteratively replaced with random values. Following these guidelines, a steady state and dynamic update strategy for PSO algorithms is proposed: only the least fit particle and its neighbors are updated and evaluated in each time-step; the remaining particles maintain the same position and fitness, unless they meet the update criterion. The steady state PSO was tested on a set of unimodal, multimodal, noisy and rotated benchmark functions, significantly improving the quality of results and convergence speed of the standard PSOs and more sophisticated PSOs with dynamic parameters and neighborhood. A sensitivity analysis of the parameters confirms the performance enhancement with different parameter settings and scalability tests show that the algorithm behavior is consistent throughout a substantial range of solution vector dimensions.

Efficiency of the Bethesda System for Thyroid Cytopathology. / Rendimiento del sistema Bethesda en el diagnóstico citopatológico del nódulo tiroideo.

INTRODUCTION: Fine-needle aspiration biopsies are a key tool for preoperative assessment of thyroid nodules, and the Bethesda system is the preferred method to report cytological analysis. The purpose of this study is to assess the efficiency of the Bethesda system to identify the malignancy risk of thyroid nodules. METHODS: Patients who underwent thyroid surgery between June 2010 and June 2017 were included. Samples were classified into 6categories according to rates of malignancy associated with each diagnostic category. In order to investigate the correlation between categories, a statistical analysis compared the categories with pathology reports. Diagnostic indicators were calculated as a screening test (categories IV, V, VI as true-positive) and as a method to identify malignancy (V, VI as true-positive). RESULTS: In a series of 522 patients, we found 184 (35.2%) malignant tumours, papillary carcinoma being the most prevalent with 155 cases (84.2%). Malignant rates for diagnostic categories were: I, 0%; II, 1.5%; III, 6.4%; IV, 31%; V, 86.5%; VI, 100%. A robust correlation was identified between categories on statistical analysis. For the «screening test¼ analysis, sensitivity was 98.9%, specificity 84.4%, positive predictive value 69.6%, negative predictive value 99.5%, and diagnostic accuracy 88.2%. Analysing the accuracy to detect malignancy, values were: sensitivity 98.6%, specificity 97.6%, positive predictive value 93.5%, negative predictive value 99.5%, diagnostic accuracy 97.9%. CONCLUSION: The Bethesda system is a clear and reliable approach to report thyroid cytology and therefore is an effective tool to identify malignancy risk and guide clinical management.

Análisis de la mezcla de alcoholes en motor diésel

Debido a que el futuro del petróleo es incierto, en la búsqueda de los combustibles alternativos se ha encontrado que el alcohol es un fuerte candidato como combustible; los alcoholes inferiores más representativos son el metanol y el etanol, los cuales han demostrado en general baja miscibilidad, por lo que pueden generar una separación de fases al ser mezclados después de un cierto tiempo. La única manera de emplearlos en un motor diésel es mezclándolos con biodiésel o con surfactantes. Por el contrario, los alcoholes superiores tienen características más adecuadas para ser mezclados o empleados en el motor diésel. Por su parte, los éteres son una buena opción cuando se trate de combustión piloto en que se considere emplear combustibles gaseosos como el biogás o el syngas en motor diésel dual. En esta investigación se exploran las alternativas que existen para mejorar las características del alcohol, por ejemplo, mezclarlo con biodiésel, biogás, agua o nanopartículas, y también se analizan las emisiones que se producen con las mezclas generadas. El objetivo es indagar las diferencias entre los alcoholes inferiores y los alcoholes superiores de cadena larga, así como las mezclas que se pueden generar para mejorar el rendimiento del motor. Los resultados afirman que los alcoholes de cadena larga tienen mejores propiedades físico-químicas que los alcoholes de cadena corta; el butanol es el único combustible que puede ser transportado y almacenado en las mismas redes de tuberías actuales de los productos petroleros existentes. También se cuenta con la opción de usar el alcohol como combustible piloto en un motor diésel dual; esto puede servir para aplicar una enorme variedad de combustibles tanto líquidos como gaseosos, lo cual hace que las opciones en su aplicación se incrementen. Como conclusión, se recomienda explorar nuevas mezclas analizando sus sinergias con varios combustibles alternativos. La posibilidad de realizar el diesterol-BED genera resultados muy alentadores, por lo que se recomienda seguir haciendo análisis sobre esa línea para encontrar la mezcla óptima.

As the future of oil is uncertain and in the search for alternative fuels, it has been found that alcohol is a strong candidate as a fuel. The most representative lower alcohols are methanol and ethanol, which have generally demonstrated low miscibility so that they can generate phase separation when mixed after a certain period of time. The only way to use them in a diesel engine is to mix them with biodiesel or surfactants. By contrast, higher alcohols have more suitable characteristics to be mixed or used in the diesel engine. In the case of ethers they are a good option when it comes to pilot combustion considering using gaseous fuels such as biogas or syngas in dual diesel engine. This research explores the alternatives that exist to improve the characteristics of alcohol as it can be mixed with biodiesel, biogas, water or nanoparticles and also analyzes the emissions that are generated with the mixtures. The aim of this research is to explore the differences between lower alcohols and long chain upper alcohols, as well as the mixtures that can be generated to improve engine performance. The results of this research claim that long-chain alcohols have better physico-chemical properties than short-chain alcohols, butanol being the only fuel that can be transported and stored in the same current pipeline networks of existing oil products. There is also the option to use alcohol as a pilot fuel in a dual diesel engine. The latter can be used to apply a huge variety of both liquid and gaseous fuels, this makes the options in its application increase. As a conclusion of this work, it is recommended to explore new mixtures analyzing their synergies with various alternative fuels. The possibility of performing diesterol-BED generates very encouraging results, therefore it is recommended to continue to perform analyses on that line to find the optimal mixture.

Na busca por combustíveis alternativos porque o futuro do petróleo é incerto, verificou-se que o álcool é um forte candidato como combustível, onde os álcoois inferiores mais representativos são o metanol e o etanol, que, em geral, demonstraram baixa miscibilidade, de modo que podem gerar separação de fase quando misturadas após um determinado período de tempo, a única forma de as utilizar num motor diesel é misturá-las com biodiesel ou tensioactivos, pelo contrário, os álcoois superiores têm características mais adequadas para serem misturados ou utilizados no motor diesel, no caso dos éteres, são uma boa opção quando se trata de combustão piloto, considerando a utilização de combustíveis gasosos, como biogás ou gás de síntese em motores a diesel duplos, esta pesquisa explora as várias alternativas que existem para melhorar as características do álcool, pois pode ser misturado com biodiesel, biogás, água ou nanopartículas e também analisa as emissões que são geradas com as misturas geradas, O objetivo desta pesquisa é explorar as diferenças entre álcoois inferiores e álcoois superiores de cadeia longa, bem como as misturas que podem ser geradas para melhorar o desempenho do motor. Os resultados desta pesquisa afirmam que os álcoois de cadeia longa têm melhores propriedades físico-químicas do que os álcoois de cadeia curta, sendo o butanol o único combustível que pode ser transportado e armazenado nas mesmas redes de gasodutos atuais que os produtos petrolíferos existentes, há também a opção de usar álcool como combustível piloto em um motor diesel duplo, Este último pode ser usado para aplicar uma enorme variedade de combustíveis líquidos e gasosos, o que aumenta as opções em sua aplicação. Como conclusão deste trabalho recomenda-se explorar novas misturas analisando suas sinergias com vários combustíveis alternativos, a possibilidade de realizar diesterol-BED gera resultados muito encorajadores, portanto, recomenda-se continuar a realizar análises nessa linha para encontrar a mistura ideal.

[Prevalences of hepatitis virus coinfection and indications for chronic hepatitis C virus treatment and liver transplantation in Spanish HIV-infected patients. The GESIDA 29/02 and FIPSE 12185/01 Multicenter Study]. / Estudio multicéntrico sobre prevalencia de las coinfecciones por virus de hepatitis, indicación de tratamiento de hepatitis crónica C y necesidad de trasplante hepático en pacientes infectados por el VIH en España. Estudio GESIDA 29/02-FIPSE 12185/01.

INTRODUCTION: The aims of this study were to estimate the prevalence of HIV and hepatitis virus coinfection in the Spanish population and to determine the percentage of patients who are candidates for chronic hepatitis C virus (HCV) treatment and liver transplantation within this population. METHODS: A cross-sectional study was performed in 2002 in two Spanish populations of HIV-infected patients: 1,260 patients from 39 centers throughout Spain (P1) and 1,560 patients from three tertiary teaching hospitals in Madrid (P2). RESULTS: The following hepatitis A virus (HAV), hepatitis B virus (HBV) and HCV serological prevalence were found in the P1 and P2 groups, respectively: HAV-IgG antibodies: 74% and 78%; HBsAg1: 4.9% and 4.8%; HBsAg-, anti-HBc1, anti-HBs1: 39% and 39%; HBsAg-, anti-HBc1, anti-HBs-: 25% and 31%; HBsAg-, anti-HBc-, anti-HBs1: 7% and 8%; HBsAg-, anti-HBc-, anti-HBs-: 22% and 16%. Anti-HCV1: 61% and 65%, respectively. Of the patients with positive HCV serology, 88.8% and 84.6% of each group were positive for HCV-RNA by polymerase chain reaction. Multiple coinfections with hepatitis viruses were found in 3.2% and 2.8%, respectively; of these, 70% and 78% had coinfection with HBV, HCV and HDV. Liver cirrhosis was found in 5.8% and 9.6% of the patients coinfected with HIV and HCV, respectively. Liver transplant was indicated in approximately one out of every six coinfected patients with liver cirrhosis. The 43 and 37% of the HCV coinfected patients were good candidates for anti-HCV treatment, but only 14% and 15% of patients had initiated it. CONCLUSIONS: A high percentage of HIV-infected patients in Spain were coinfected with hepatitis viruses, especially HCV. The number of possible candidates for liver transplantation is rising and could increase in the next few years. In the future, greater efforts to treat HIV-and hepatitis virus-coinfected patients will be required.