Functional modeling of high-dimensional data: a Manifold Learning approach

This article belongs to the Special Issue Methodological and Applied Contributions on Stochastic Modelling and ForecastingThis paper introduces stringing via Manifold Learning (ML-stringing), an alternative to the original stringing based on Unidimensional Scaling (UDS). Our proposal is framed within a wider class of methods that map high-dimensional observations to the infinite space of functions,allowing the use of Functional Data Analysis (FDA). Stringing handles general high-dimensional data as scrambled realizations of an unknown stochastic process. Therefore, the essential feature of the method is a rearrangement of the observed values. Motivated by the linear nature of UDS and the increasing number of applications to biosciences (e.g., functional modeling of gene expression arrays and single nucleotide polymorphisms, or the classification of neuroimages) we aim to recover more complex relations between predictors through ML. In simulation studies, it is shown that MLstringing achieves higher-quality orderings and that, in general, this leads to improvements in the functional representation and modeling of the data. The versatility of our method is also illustrated with an application to a colon cancer study that deals with high-dimensional gene expression arrays.This paper shows that ML-stringing is a feasible alternative to the UDS-based version. Also, it opens a window to new contributions to the field of FDA and the study of high-dimensional data.This research was funded in part by Ministerio de Ciencia, Innovación y Universidades grant numbers PID2019-104901RB-I00 and MTM2017-88708-P

Cystic Fibrosis: actual treatment and future perspectives with nanotechnology

Introducción: Actualmente, los tratamientos existentes para tratar la fibrosis quística (FQ) están diseñados para controlar sus síntomas, consistentes principalmente en retención de moco e infección crónica. Se propone la vía pulmonar como alternativa para la administración de los fármacos, principalmente antimicrobianos. Sin embargo, su rápido aclaramiento, que conduce a niveles bajos de fármaco e incremento de los regímenes posológicos, así como la aparición de efectos adversos, hacen de la nanotecnología una estrategia interesante para esta enfermedad. Objetivo: estudiar y analizar los diferentes sistemas nanoparticulares existentes para su uso por vía pulmonar, concretando en el uso de sistemas lipídicos para el tratamiento de la FQ. Método: se realizó una búsqueda no sistemática de artículos en diferentes bases de datos, en los últimos 10 años principalmente, siguiendo pautas establecidas de palabras clave. Resultados: Los progresos que se han conseguido en los últimos años hacen que la FQ pase a ser una enfermedad de adultos. Los tratamientos que se están usando en la actualidad están siendo cada vez más desplazados por otras alternativas, como los sistemas nanoparticulares, siendo idóneos para la administración pulmonar debido a su pequeño tamaño, su liberación sostenida y su elevada biocompatibilidad. Entre éstos, destacan los liposomas por su similitud estructural con el surfactante pulmonar, así como por su capacidad de destruir las biopelículas bacterianas. La mayoría de las formulaciones encontradas contenían un solo fármaco. Conclusión: Existen evidencias científicas que indican que la investigación debe dirigirse hacia el desarrollo de formulaciones que sean capaces de destruir la biopelícula.Introduction: Currently, the management of treatments in cystic fibrosis (CF) is mainly focused to control symptoms, which consist of mucus retention and chronic infection. The pulmonary route is proposed as an interesting alternative for administering drugs, especially antimicrobials. However, the rapid clearance of these, which leads to low drug levels and increased dosage regimens, as well as the appearance of adverse effects, make nanotechnology an interesting strategy for this disease. Objective: to study and analyze the different nanoparticulate systems available for use via the lung, specifying the use of lipid systems for the treatment of CF. Method: a non-systematic search of articles in different databases was carried out, mainly in the last 10 years, following established guidelines for selecting keywords. Results: The progress in recent years makes CF become an adult disease. Current treatments are increasingly being displaced by other alternatives, such as nanoparticular systems, being suitable for pulmonary administration due to their small size, sustained release and high biocompatibility. Among these, liposomes stand out for their structural similarity to lung surfactant, as well as for their ability to destroy bacterial biofilms. Most of the formulations contained a single drug. Conclusion: Scientific literature evidenced that research studies should be directed towards the development of formulations that are intended to destroy the biofilm

Drug Repurposing for Cancers With Limited Survival: Protocol for a Retrospective Cohort Study

Only 5% of the molecules tested in oncology phase 1 trials reach the market after an average of 7.5 years of waiting and at a cost of tens of millions of dollars. To reduce the cost and shorten the time of discovery of new treatments, drug repurposing (research with molecules already approved for another indication) and the use of secondary data (not collected for the purpose of research) have been proposed. Due to advances in informatics in clinical care, secondary data can, in some cases, be of equal quality to primary data generated through prospective studies.Objective: The objective of this study is to identify drugs currently marketed for other indications that may have an effect on the prognosis of patients with cancer.Methods: We plan to monitor a cohort of patients with high-lethality cancers treated in the public health system of Catalonia between 2006 and 2012, retrospectively, for survival for 5 years after diagnosis or until death. A control cohort, comprising people without cancer, will also be retrospectively monitored for 5 years. The following study variables will be extracted from different population databases: type of cancer (patients with cancer cohort), date and cause of death, pharmacological treatment, sex, age, and place of residence. During the first stage of statistical analysis of the patients with cancer cohort, the drugs consumed by the long-term survivors (alive at 5 years) will be compared with those consumed by nonsurvivors. In the second stage, the survival associated with the consumption of each relevant drug will be analyzed. For the analyses, groups will be matched for potentially confounding variables, and multivariate analyses will be performed to adjust for residual confounding variables if necessary. The control cohort will be used to verify whether the associations found are exclusive to patients with cancer or whether they also occur in patients without cancer.Results: We anticipate discovering multiple significant associations between commonly used drugs and the survival outcomes of patients with cancer. We expect to publish the initial results in the first half of 2024.Conclusions: This retrospective study may identify several commonly used drugs as candidates for repurposing in the treatment of various cancers. All analyses are considered exploratory; therefore, the results will have to be confirmed in subsequent clinical trials. However, the results of this study may accelerate drug discovery in oncology

Estudio fenológico y caracterización morfológica de variedades tradicionales de manzano y melocotonero

Las variedades locales de frutales seleccionadas a lo largo de los años por los agricultores, son muy interesantes para preservar la biodiversidad y los recursos fitogenéticos, ya que presentan unas características organolépticas peculiares y un valor cultural irremplazable. En 2007 se inició un trabajo de recuperación de variedades tradicionales de frutales en Andalucía (Proyecto INIA, RF2007-00027- C06-05) que contempla su prospección, localización, recogida de material vegetal, caracterización morfológica y molecular, multiplicación, documentación y mantenimiento en colección. En este trabajo se han caracterizado morfológicamente mediante caracteres UPOV las flores, hojas y ramos de un año, de cinco variedades tradicionales de manzano (Malus x domestica Borkh.) y dos de melocotonero [Prunus persica (L) Batsch], no estudiadas con anterioridad. Se ha evaluado la floración en la campaña 2011 y se han realizado los fenogramas correspondientesMICINN, INIA y Fondos FEDE

Twitter como herramienta de apoyo a la docencia

Memoria ID-0062. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2017-2018

Tisosa: A suburban site in the surroundings of Segisamo (Sasamón, Burgos)

RESUMEN: Los trabajos de prospección y de fotointerpretación han permitido localizar un nuevo yacimiento en el entorno de Sasamón, que pudo estar relacionado con la fundación de la ciudad y perduró en el tiempo como indica la presencia de terra sigillata hispánica altoimperial y terra sigillata hispánica tardía. El yacimiento representa un elemento novedoso dentro del proceso de ocupación del espacio en la región, según una estrategia claramente romana. En este trabajo, además de aspectos metodológicos, se aborda el estudio de los materiales, planteando algunas hipótesis sobre su finalidad y cronología.ABSTRACT: Pedological surveys and oblique aerial image interpretation have led us to the location of a new site in the suburban area of Sasamon. Its original function may have been related with to the foundation of the city of Segisamo and afterwards lasted throughout several centuries according to the presence of Late Hispanic sigillata. The site represents new findings on the Roman settlement pattern in the area. In addition to methodological issues, this paper addresses the study of the material culture in order to propose hypothesis about function and chronology

Cardiovascular-related proteomic changes in ECFCs exposed to the serum of COVID-19 patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection significantly affects the cardiovascular system, causing vascular damage and thromboembolic events in critical patients. Endothelial dysfunction represents one of the first steps in response to COVID-19 that might lead to cardiovascular complications and long-term sequelae. However, despite the enormous efforts in the last two years, the molecular mechanisms involved in such processes remain poorly understood. Herein, we analyzed the protein changes taking place in endothelial colony forming cells (ECFCs) after the incubation with the serum from individuals infected with COVID-19, whether asymptomatic or critical patients, by application of a label free-quantitative proteomics approach. Specifically, ECFCs from healthy individuals were incubated ex-vivo with the serum of either COVID-19 negative donors (PCR-/IgG-, n:8), COVID-19 asymptomatic donors at different infective stages (PCR+/ IgG-, n:8and PCR-/IgG+, n:8), or hospitalized critical COVID-19 patients (n:8), followed by proteomics analysis. In total, 590 proteins were differentially expressed in ECFCs in response to all infected serums. Predictive analysis highlighted several proteins like CAPN5, SURF4, LAMP2 or MT-ND1, as highly discriminating features between the groups compared. Protein changes correlated with viral infection, RNA metabolism or autophagy, among others. Remarkably, the angiogenic potential of ECFCs in response to the infected serums was impaired, and many of the protein alterations in response to the serum of critical patients were associated with cardiovascular-related pathologies.This study was supported by GLOBALCAJA-Ayuda COVID-19; and Fondo Supera COVID-19, funded by Banco Santander and CRUE universidades, Ref. IPSA-COVID-19, and the Institute of Health Carlos III, ISCIII (PI18-00427, PI20-00716), co-funded by European Regional Development “A way to make Europe”

Prosthetic shoulder joint infection by Cutibacterium acnes: does rifampin improve prognosis? a retrospective, multicenter, observational study.

This retrospective, multicenter observational study aimed to describe the outcomes of surgical and medical treatment of C. acnes-related prosthetic joint infection (PJI) and the potential benefit of rifampin-based therapies. Patients with C. acnes-related PJI who were diagnosed and treated between January 2003 and December 2016 were included. We analyzed 44 patients with C. acnes-related PJI (median age, 67.5 years (IQR, 57.3-75.8)); 75% were men. The majority (61.4%) had late chronic infection according to the Tsukayama classification. All patients received surgical treatment, and most antibiotic regimens (43.2%) included β-lactam. Thirty-four patients (87.17%) were cured; five showed relapse. The final outcome (cure vs. relapse) showed a nonsignificant trend toward higher failure frequency among patients with previous prosthesis (OR: 6.89; 95% CI: 0.80-58.90) or prior surgery and infection (OR: 10.67; 95% IC: 1.08-105.28) in the same joint. Patients treated with clindamycin alone had a higher recurrence rate (40.0% vs. 8.8%). Rifampin treatment did not decrease recurrence in patients treated with β-lactams. Prior prosthesis, surgery, or infection in the same joint might be related to recurrence, and rifampin-based combinations do not seem to improve prognosis. Debridement and implant retention appear a safe option for surgical treatment of early PJI

Integrated use of residues from olive mill and winery for lipase production by solid state fermentation with Aspergillus sp

Two phase olive mill waste (TPOMW) is presently the major waste produced by the olive mill industry. This waste has potential to be used as substrate for solid state fermentation (SSF) despite of its high concentration of phenolic compounds and low nitrogen content. In this work, it is demonstrated that mixtures of TPOMW with winery wastes support the production of lipase by Aspergillus spp. By agar plate screening, Aspergillus niger MUM 03.58, Aspergillus ibericus MUM 03.49 and Aspergillus uvarum MUM 08.01 were chosen for lipase production by SSF. Plackett-Burman experimental design was employed to evaluate the effect of substrate composition and time on lipase production. The highest amounts of lipase were produced by A. ibericus on a mixture of TPOMW, urea and exhausted grape mark (EGM). Urea was found to be the most influent factor for the lipase production. Further optimization of lipase production by A. ibericus using a full factorial design (32) conducted to optimal conditions of substrate composition (0.073 g urea/g and 25% of EGM) achieving 18.67 U/g of lipolytic activity.Jose Manuel Salgado is grateful for Postdoctoral fellowship (EX-2010-0402) of Education Ministry of Spanish Government. Luis Abrunhosa was supported by the grant SFRH/BPD/43922/2008 from Fundacao para a Ciencia e Tecnologia-FCT, Portugal. Authors thank Fundacao para a Ciencia e a Tecnologia (FCT) for financial support through the project FCT Pest-OE/EQB/LA0023/2011

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19