Search

Background: Nowadays, gene expression analysis is one of the most promising pillars for understanding and uncovering the mechanisms underlying the development and spread of cancer. In this sense, Next Generation Sequencing technologies, such as RNA-Seq, are currently leading the market due to their precision and cost. Nevertheless, there is still an enormous amount of non-analyzed data obtained from older technologies, such as Microarray, which could still be useful to extract relevant knowledge. Methods: Throughout this research, a complete machine learning methodology to cross-evaluate the compatibility between both RNA-Seq and Microarray sequencing technologies is described and implemented. In order to show a real application of the designed pipeline, a lung cancer case study is addressed by considering two detected subtypes: adenocarcinoma and squamous cell carcinoma. Transcriptomic datasets considered for our study have been obtained from the public repositories NCBI/GEO, ArrayExpress and GDC-Portal. From them, several gene experiments have been carried out with the aim of finding gene signatures for these lung cancer subtypes, linked to both transcriptomic technologies. With these DEGs selected, intelligent predictive models capable of classifying new samples belonging to these cancer subtypes have been developed. Results: The predictive models built using one technology are capable of discerning samples from a different technology. The classification results are evaluated in terms of accuracy, F1-score and ROC curves along with AUC. Finally, the biological information of the gene sets obtained and their relationship with lung cancer are reviewed, encountering strong biological evidence linking them to the disease. Conclusion: Our method has the capability of finding strong gene signatures which are also independent of the transcriptomic technology used to develop the analysis. In addition, our article highlights the potential of using heterogeneous transcriptomic data to increase the amount of samples for the studies, increasing the statistical significance of the results.

Made available in DSpace on 2022-04-28T19:46:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-09 Background and ObjectivesPeople with multiple sclerosis MS are a vulnerable group for severe coronavirus disease 2019 COVID-19, particularly those taking immunosuppressive disease-modifying therapies DMTs. We examined the characteristics of COVID-19 severity in an international sample of people with MS.MethodsData from 12 data sources in 28 countries were aggregated sources could include patients from 1-12 countries. Demographic age, sex, clinical MS phenotype, disability, and DMT untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit ICU admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale EDSS score.ResultsSix hundred fifty-seven 28.1% with suspected and 1,683 61.9% with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02 and ICU admission aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89, although only rituximab was associated with higher risk of artificial ventilation aOR 4.00, 95% CI 1.54-10.39. Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07 and ICU admission aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23, but only rituximab was associated with artificial ventilation aOR 6.15, 95% CI 3.09-12.27. Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92 and ICU admission aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91, but only rituximab was associated with ventilation aOR 5.52, 95% CI 1.71-17.84. Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity.DiscussionUsing the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19. CORe Department of Medicine and Neuroepidemiology Unit Melbourne School of Population and Global Health Menzies Institute for Medical Research University of Tasmania ESAT-STADIUS KU Leuven Department of Neurology Melbourne MS Centre Royal Melbourne Hospital MS International Federation Department of Clinical Neuroscience Swedish MS Registry Department of Neurology CHU Pontchaillou Karolinska Institutet Biomedical Research Institute-Data Science Institute Hasselt University Department of Medical Informatics University Medical Center Department of Computer Science and AI KU Leuven QMENTA Medpace Reference Laboratories Molecular Unit IConquerMS People-Powered Research Network Accelerated Cure Project for MS NeuroTransData Study Group NeuroTransData German MS-Register by the National MS Society MS Forschungs- und Projektentwicklungs-gGmbH MS Register Swansea University COViMS Division of Biostatistics Washington University in St. Louis Mellen Center for Multiple Sclerosis Cleveland Clinic Department of Neuroscience Central Clinical School Monash University Al-Amiri Hospital Kuwait City Dokuz Eylul University Neurology Department Hospital Universitario de CEMIC RELACOEM Australian MS Longitudinal Study Menzies Institute for Medical Research University of Tasmania Bulgarian SmartMS COVID-19 Dataset ABEM-Brazilian MS Patients Association Danish Multiple Sclerosis Registry Department of Neurology University Hospital Rigshospitalet Universidade Estadual Paulista Unesp Faculdade de Medicina REDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders Irmandade da Santa Casa de Misericórdia de São Paulo Multiple Sclerosis University Center Ramos Mejia Hospital-EMA Imperial College Swansea University Mental Health Area MS and Demyelinating Diseases Hospital Británico de Buenos Aires EMA Servei de Neurologia-Neuroimmunologia Centre d'Esclerosi Múltiple de Catalunya Cemcat Vall d'Hebron Institut de Recerca Vall d'Hebron Hospital Universitari Universitat Autònoma de Barcelona Institute of Experimental Neurology Ospedale San Raffaele Universidade Estadual Paulista Unesp Faculdade de Medicina

The objectives of the present study were to describe the frequency of aggressive multiple sclerosis (aMS) as well as to compare clinical and radiological characteristics in aMS and non-aMS patients included in RelevarEM (NCT03375177).The eligible study population and cohort selection included adult-onset patients (≥18 years) with definite MS. AMS were defined as those reaching confirmed EDSS ≥ 6 within 5 years from symptom onset. Confirmation was achieved when a subsequent EDSS ≥ 6 was recorded at least six months later but within 5 years of the first clinical presentation. AMS and non-aMS were compared using the χ2 test for categorical and the Mann-Whitney for continuous variables at MS onset and multivariable analysis was performed using forward stepwise logistic regression with baseline characteristics at disease onset.A total of 2158 patients with MS were included: 74 aMS and 2084 non-aMS. The prevalence of aMS in our cohort was 3.4% (95%CI 2.7-4.2). AMS were more likely to be male (p = 0.003), older at MS onset (p 0.001), have primary progressive MS (PPMS) phenotype (p = 0.03), multifocal presentation (p 0.001), and spinal cord as well as infratentorial lesions at MRI during disease onset (p = 0.004 and p = 0.002, respectively).3.4% of our patient population could be considered aMS. Men, patients older at symptom onset, multifocal presentation, PPMS phenotype, and spinal cord as well as brainstem lesions on MRI at clinical presentation all had higher odds of having aMS.

Photothermal radiometric spectroscopy was employed for characterizing an aluminum automotive piston with a steel insert. Amplitude and phase thermal property differences allowed the mapping of both metals. Thermal images were generated by using table stages x-y movement. The thermal wave penetrated more deeply in aluminum than in steel. Results demonstrated that this relatively unknown, non-intrusively, non-contact, and non-destructive technique can be used for characterizing a wide variety of metals and other materials.

We analyze the differential brain volume changes in highly active multiple sclerosis (HAMS) vs. non-HAMS patients during the disease onset.HAMS was defined as: a) patients with 1 relapse in the previous year and at least 1 T1 gadolinium-enhancing lesion or 9 or more T2 lesions while on therapy with other disease modifying treatment (DMD); or b) patients with 2 or more relapses in the previous year, whether on DMD or not. High-resolution T1 weighted MRI scans were acquired at onset and every 12 months for 2 years. Lesion load and brain volume measurements were determined. At onset, gray matter volume (GMV) and white matter volume (WMV) tissue volumes were calculated using the SIENAX. Longitudinal changes were estimated by using SIENA to calculate the percentage of brain volume loss. Differences between volumes per group at onset and at the end of the follow up were established.64 patients, mean age 38.4 years, 35 (57%) women were included. A total of 14 (21%) were classified as HAMS. At onset, HAMS patients showed lower GMV and WMV volume compared with non-HAMS patients (p = 0.003 and p = 0.01, respectively). During the follow up, HAMS patients showed a higher decrease in GM volume compared with non-HAMS patients (-0.61 vs. - 0.77, p 0.001) independent from new lesion as well as relapse rate activity during follow up.HAMS increased rates of GMV atrophy over 24 months compared to non-HAMS patients independent from relapse rate and new T2 lesions.

Objective: The objective of this study was to assess if the presence of new lesions and their topography on the reference MRI have a prognostic value regarding disease activity during the follow up in relapsing remitting multiple sclerosis (RRMS) patients.Methods: Retrospective cohort study that included patients with RRMS who had a reference MRI (performed at 6 months from the onset of a DMT) and radiological and clinical follow up for at least two years. We identified the number of new MRI lesions and their topography at reference MRI and during the follow up. Cox proportional hazards model analysis was used to evaluate the association between new lesions on reference MRI and the appearance of new lesions and/or clinical relapses at 24-month follow-up.Results: 56 patients were included, 13 (23.2%) showed new lesions in the reference MRI. The presence of new lesions at reference MRI predicted the occurrence of new lesions at month 24 (HR 3.1, CI 95% 2.5-5.8). The number of lesions and the infratentorial topography at reference MRI were associated with an increased risk of new radiological activity during follow up (HR 3.5, IC95% 3.1-6.1 and HR 2.4, IC95% 1.9-2.7 respectively).Conclusion: New lesions at the reference MRI in terms of number and topography increase the risk of radiological disease activity during the follow up.

The objective of this study was to describe and compare the baseline epidemiological data of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients included in RelevarEM (Clinical Trials registry number NCT03375177). RelevarEM is a longitudinal, strictly observational MS and NMOSD registry in Argentina. Epidemiological and comorbidity data from MS and NMOSD patients were described and compared. For comorbidities, the Charlson comorbidity index (CCI) was used to calculate the burden at entry. CCI was stratified in 0 and ≥ 1 and described for the entire cohort. A total of 1588 and 75 MS and NMOSD patients (respectively) were included. For MS patients, the mean age was 42 ± 7 years, female sex 65.3%, mean EDSS 2, and mean disease duration 8 ± 6 years. In NMOSD, the mean age was 40 ± 7 years, female sex 78.7%, mean disease duration 5 ± 3.5 years, and mean EDSS 2.5. The most frequent MS phenotype was RRMS in 82.4%. In MS, the CCI was 0 in 85.8.2% while ≥ 1 was in 14.2% of patients. Regarding phenotype stratification, CCI ≥ 1 was 3.9% in CIS, 13.5% in RRMS, 28.7% in SPMS, and 17.4% in PPMS (p

This article shows an approach to the three-dimensional modelling of a sugarcane mill and its associated steam engine, designed by the Robey and Co. engineering company in 1869. In order to obtain the 3D CAD model of said invention, CATIA V5 R20 software has been employed. Various sources of starting material, from the basis of this research and found in the process of searching for relevant information, provide information on the main elements, operating conditions, and mechanism of the machine. Thanks to the three-dimensional geometric modelling carried out, it has been possible to explain, in detail, both its operation and the final assembly of the invention through the assemblies of its different subsets, thereby obtaining a virtual recreation that shows its operation. Likewise, a study has been carried out, from a mechanical engineering viewpoint, of the gear train that transmitted the movement, in order to ascertain the compression force exerted on the sugar cane. This research, related to industrial archaeology, therefore, enables the reader to understand a machine that constituted a milestone in the sugarcane industry, while paying tribute to the English engineer, Robert Robey

BACKGROUND AND PURPOSE Optic neuritis (ON) is often the initial symptom of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD). We aimed to compare the frequency and pattern of chiasmatic lesions in MOGAD-related ON (MOGAD-ON) and NMOSD-related ON (NMOSD-ON) using conventional brain imaging (magnetic resonance imaging [MRI]) in Latin America (LATAM). METHODS We reviewed the medical records and brain MRI (≤30 days from ON onset) of patients with a first event of MOGAD-ON and NMOSD-ON. Patients from Argentina (n = 72), Chile (n = 21), Ecuador (n = 31), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 82) were included. Antibody status was tested using a cell-based assay. Demographic, clinical, imaging and prognostic (as measured by the Visual Functional System Score [VFSS] of the Expanded Disability Status Scale) data were compared. RESULTS A total of 246 patients (208 NMOSD and 38 MOGAD) were included. No differences were found in gender and ethnicity between the groups. We observed chiasmatic lesions in 66/208 (31.7%) NMOSD-ON and in 5/38 (13.1%) MOGAD-ON patients (p = 0.01). Of these patients with chiasmatic lesions, 54/66 (81.8%) and 4/5 had associated longitudinally extensive optic nerve lesions, 45/66 (68%) and 4/5 had bilateral lesions, and 31/66 (47%) and 4/5 showed gadolinium-enhancing chiasmatic lesions, respectively. A positive correlation was observed between VFSS and presence of bilateral (r = 0,28, p

This work was funded by the Spanish Ministry of Sciences, Innovation and Universities under Grant RTI2018-101674B-I00 as part of project "Computer Architectures and Machine Learning-based solutions for complex challenges in Bioinformatics, Biotechnology and Biomedicine" and by the Government of Andalusia under the grant CV20-64934 as part of the project "Development of an intelligence platform for the integration of heterogenous sources of information (images, genetic information and proteomics) for the characterization and prediction of COVID-19 patients' virulence and pathogenicity". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript., Background: Adenocarcinoma and squamous cell carcinoma are the two most prevalent lung cancer types, and their distinction requires different screenings, such as the visual inspection of histology slides by an expert pathologist, the analysis of gene expression or computer tomography scans, among others. In recent years, there has been an increasing gathering of biological data for decision support systems in the diagnosis (e.g. histology imaging, next-generation sequencing technologies data, clinical information, etc.). Using all these sources to design integrative classification approaches may improve the final diagnosis of a patient, in the same way that doctors can use multiple types of screenings to reach a final decision on the diagnosis. In this work, we present a late fusion classification model using histology and RNA-Seq data for adenocarcinoma, squamous-cell carcinoma and healthy lung tissue. Results: The classification model improves results over using each source of information separately, being able to reduce the diagnosis error rate up to a 64% over the isolate histology classifier and a 24% over the isolate gene expression classifier, reaching a mean F1-Score of 95.19% and a mean AUC of 0.991. Conclusions: These findings suggest that a classification model using a late fusion methodology can considerably help clinicians in the diagnosis between the aforementioned lung cancer cancer subtypes over using each source of information separately. This approach can also be applied to any cancer type or disease with heterogeneous sources of information., Spanish Ministry of Sciences, Innovation and Universities RTI2018-101674B-I00, Government of Andalusia CV20-64934

Background People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods Data from 12 data-sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl-fumarate, glatiramer-acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other) covariates were queried, alongside COVID-19 hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression, adjusted for age, sex, MS phenotype, and EDSS. Results 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Among suspected+confirmed/confirmed-only COVID-19, 20.9%/26.9% were hospitalised, 5.4%/7.2% were admitted to ICU, 4.1%/5.4% required artificial ventilation, and 3.2%/3.9% died. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl-fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Conclusions Despite the cross-sectional design of this study, the internal and external consistency of these results with prior studies suggests their use may be a risk factor for more severe COVID-19. Key messages Anti-CD20 DMTs may be associated with worse COVID-19 severity amongst people with multiple sclerosis.

Background The objective of our study was to describe the availability of diagnostic tests and treatment for MS and NMOSD in Latin America (LATAM). Methods A survey instrument was used in a sample of physicians from LATAM countries. The goal of the survey was to understand availability of: 1) imaging tests for diagnosing MS and NMOSD and its barriers; 2) diagnostic laboratory tests for diagnosing MS and NMOSD and its barriers; and 3) treatments for MS and NMOSD in the acute and chronic phases of the disease. Results Responses were received from 80 physicians. AQP4-ab test was available in 54% of the countries and MOG-ab test in 42%. All of countries had available use of high doses of intravenous methylprednisolone, oral steroids, plasmapheresis, and intravenous immunoglobulins for relapses. For NMOSD, 93% of the countries were able to use azathioprine and mycophenolate mofetil, and 87% rituximab. In MS, 93% of countries had available to them IFN beta, 69% glatiramer acetate, 75% teriflunomide, 93% fingolimod, 69% dimethyl-fumarate, 75% cladribine, 69% natalizumab, 93% ocrelizumab and 81% alemtuzumab. The most common challenge and barrier identified was the cost of medications. Conclusion The present study allows an understanding of the delivery of care for MS and NMOSD in the region.

We aimed to analyze the accumulative risk of MRI and OB factors for evolution from RIS to MS in subjects included in the Argentinean MS registry (NCT03375177). RIS subjects were identified according to RIS diagnosis criteria. Subjects were longitudinally followed with clinical and MRI at intervals of 6 months. Time from RIS identification to the first clinical event was estimated using Kaplan–Meier. Multivariable Cox regression models were created to assess the independent predictive value of demographic characteristics, as well as clinical, OB and MRI data on time to the first clinical event. The single and increased risk factor of evolution of RIS was quantified. A total of 88 RIS subjects, mean follow-up time 42 ± 4 months were included. 39 (44.3%) and 23 (26.1%) had a new MRI lesion or a clinical event, respectively, during the follow-up. OB (HR 5.9, 95% CI 1.29–10.1, p = 0.004), infratentorial lesions (HR 3.7, 95% CI 1.09–7.5) and spinal cord lesions (HR 5.3, 95% CI 1.4–8.2, p = 0.01) at RIS identification were independent predictors associated with a subsequent clinical event. The accumulative risk showed that when two of the three factors (OB, infratentorial or spinal cord lesions) were present the HR was 10.4, 95% CI 4.4–22, p

Recent years have witnessed a widespread in the use of interval type-2 fuzzy logic systems (IT2 FLSs) in real-world applications. It has been shown recently that interval type-2 fuzzy sets (IT2 FSs) are more general than interval-valued fuzzy sets (IV FSs) [1] . Hence, there is a need to explore the capabilities of the more general forms of IT2 FSs (beyond IV FSs) and the applications areas they will be more suitable for. In addition, there is a need to develop the theory of the general forms of IT2 FLSs (gfIT2 FLSs), which employ IT2 FSs that are not equivalent to IV FSs and can have nonconvex secondary membership functions (MFs). Although these systems could be considered within the scope of general type-2 FLSs (GT2 FLSs), the practical implementation of GT2 FLSs has traditionally required the secondary MFs to be convex and normal type-1 fuzzy sets (T1 FSs). In addition, the type-reduction operation still presents a challenge for GT2 FLSs because of its computational complexity. In this paper, we present a complete framework for a type-2 FLS that uses the most recent perception of IT2 FSs (the so called general forms of interval type-2 fuzzy sets, gfIT2 FSs), whose secondary grades can be nonconvex T1 FSs. This framework includes new equations for the meet and join operations of gfIT2 FSs, as well as a new type reduction procedure for the type-2 FLS involving gfIT2 FSs. In addition, we present the type-2 FLS operation for singleton and nonsingleton fuzzification. We will introduce the various operations employed within a gfIT2 FLSs, from fuzzification (including singleton and nonsingleton) to inference, type-reduction, and defuzzification. We will also present two examples in which these gfIT2 FSs arise naturally when modeling sonar sensors input noise and the antecedents/consequents from a survey including different users.

The present article will analyze the voice of the narrator from the rhizomatic figure (Deleuze and Guattari) to determine its non-place in the construction of narrative scenes in the new performative forms of literary expression. Therefore, this condition will be reviewed from two Benjaminian notions, the allegory and the quotation to determine that the idea of the body is -centrally concentrated in L. Illuminated- a correlation between language and subject: the disappearance of the subject is the disappearance of his / her language, epistemological symmetry that gives rise in Chilean narrative to a performative writing.

Despite that different registries already exist in various countries in Europe and North America, no ongoing nationwide registry exists in Latin America (LATAM), a region where the disease behaves differently than in other regions. The objective of this document is to describe the methodology behind RelevarEM, the first nationwide MS registry in Argentina and LATAM. METHODS: In this article, we described the creation, implementation and data management of the nationwide MS registry in Argentina. The registry contains information on the structure, ethical aspects, implementation and variables of the registry (Clinical Trials registry number NCT NCT03375177). CONCLUSION: RelevarEM is the first MS nationwide registry in Argentina, as well as in LATAM, with the objective of providing reliable real-world data of MS in the country.

The objective of the present study was to identify the frequency of MS patients in Latin America (LATAM) that received the influenza vaccine during the most recent season and the reasons related to non-vaccination. Cross-sectional study between November and December 2020 in a large cohort of MS patients from LATAM. Patients responded about recommendation of receiving influenza vaccine and the use of it as well as reasons for not using the vaccine. Four hundred twelve MS patients were included in the analysis. 47.3% of patients were recommended to receive the vaccine from the treating physician. Nearly 54% of patients did not receive the influenza vaccine, and the most frequent cause was that it was neither recommended nor mentioned by the treating physician (27.4%). Female gender (OR = 2.3, 95%CI 1.4–3.8, p = 0.001) was associated with an increased risk of recommendation, while a progressive form of MS and higher EDSS decreased the risk (OR = 0.49, 95%CI 0.27–0.90, p = 0.023; OR = 0.65, 95%CI 0.55–0.97, p = 0.02, respectively). Despite the evidence to recommend the influenza vaccine in MS patients, a limited number of patients in clinical practice received such recommendation. Supplementary information The online version contains supplementary material available at 10.1007/s13365-021-01011-w.

We report COVID-19 presentation, course and outcomes in teriflunomide-treated MS patients in Argentina. Methods: descriptive, retrospective, multicentre, study that included MS patients receiving teriflunomide who developed COVID-19, with clinical follow-up at reference MS centres, also listed in a nationwide registry. Results: Eighteen MS patients on teriflunomide treatment, from eight MS centres developed COVID-19. The mean age was 41,2 years and 72% of them were female; 94% had diagnosis of relapsing-remitting MS and 6% presented a radiologically isolated syndrome. Median EDSS was 2 (range 0-5.5). The average time on teriflunomide therapy was 3 years. COVID-19 diagnosis was confirmed with nasal swab in 61%. None required hospitalization and they completely recovered from the acute-phase within 7-14 days. All the patients continued their teriflunomide therapy during COVID-19 course. No MS relapses occurred during or after COVID-19 course. Conclusion: Our report adds to the evidence that COVID-19 is mild in patients receiving teriflunomide therapy and that continuing with teriflunomide therapy during Sars-CoV-2 infection is safe and advisable for MS patients.

BACKGROUND Neuromyelitis optica spectrum disorders (NMOSD) is an increasing diagnostic and therapeutic challenge in Latin America (LATAM). Despite the heterogeneity of this population, ethnic and socioeconomic commonalities exist, and epidemiologic studies from the region have had a limited geographic and population outreach. Identification of some aspects from the entire region are lacking. OBJECTIVES To determine ethnic, clinical characteristics, and utilization of diagnostic tools and types of therapy for patients with NMOSD in the entire Latin American region. METHODS The Latin American Committee for Treatment and Research in MS (LACTRIMS) created an exploratory investigational survey addressed by Invitation to NMOSD Latin American experts identified through diverse sources. Data input closed after 30 days from the initial invitation. The questionnaire allowed use of absolute numbers or percentages. Multiple option responses covering 25 themes included definition of type of practice; number of NMOSD cases; ethnicity; utilization of the 2015 International Panel criteria for the diagnosis of Neuromyelitis optica (IPDN); clinical phenotypes; methodology utilized for determination of anti-Aquaporin-4 (anti- AQP4) antibodies serological testing, and if this was performed locally or processed abroad; treatment of relapses, and long-term management were surveyed. RESULTS We identified 62 investigators from 21 countries reporting information from 2154 patients (utilizing the IPDN criteria in 93.9% of cases), which were categorized in two geographical regions: North-Central, including the Caribbean (NCC), and South America (SA). Ethnic identification disclosed Mestizos 61.4% as the main group. The most common presenting symptoms were concomitant presence of optic neuritis and transverse myelitis in 31.8% (p=0.95); only optic neuritis in 31.4% (more common in SA), p

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) has been investigated in many autoimmune conditions as a biomarker of inflammation and/or disease activity. The role of NLR in AQP4-IgG-positive neuromyelitis optica spectrum disorders (NMOSD) is far from clear. In this study, NLR was evaluated in patients with AQP4-IgG-positive NMOSD at disease onset and its prognostic impact was subsequently assessed.MethodsIn this multicenter study, we retrospectively included all recent/newly diagnosed treatment-naïve patients with AQP4-IgG-positive NMOSD (n=90) from three different countries in Latin America (LATAM): Argentina, Ecuador, and Mexico. NLR was compared between AQP4-IgG-positive NMOSD and healthy controls (HC, n = 365). Demographic, clinical, paraclinical (including imaging), and prognostic data at 12 and 24 months were also evaluated. Multivariate regression analysis was used to describe and identify independent associations between the log-transformed NLR and clinical (relapses and EDSS) and imaging (new/enlarging and/or contrast-enhancing MRI lesions) outcomes.ResultsNLR was higher in NMOSD patients during the first attack compared with HC (2.9 ± 1.6 vs 1.8 ± 0.6; pConclusionsIn this cohort of LATAM patients with AQP4-IgG-positive NMOSD, NLR was abnormally high in attacks but also during follow-up. However, a high NLR was not an independent predictor of clinical or imaging outcomes in our models.

BackgroundPeople with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS.MethodsData from 12 data-sources in 28 countries were aggregated. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression.Results657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29-2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36; aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death.ConclusionsUsing the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission, suggesting their use may be a risk factor for more severe COVID-19.

Background The objective of the study was to compare the interval from first symptom of MS to diagnosis, and the interval between date of diagnosis and DMD initiation with the introduction of upgraded MS diagnosis criteria. Methods retrospective cohort study. To be included, data concerning date of disease onset (first relapse), date of diagnosis (confirmed disease) and date of DMD initiation had to be available. Kaplan-Meier estimator and plots were applied. Survival probabilities were evaluated for the 2 diagnosis epoch groups according to the diagnostic criteria advised at the time: group 1, for diagnosis performed between 2005-2009 (2005 revised McDonald criteria) and group 2, for diagnosis performed between 2010-2017 (2010 revised McDonald criteria). Results 654 patients were included (278 in group 1 and 308 in group 2). The mean time from disease onset to diagnosis in group 1 was 11 ± 4 vs. 7 ± 3 months (p = 0.001). Mean time from disease diagnosis to first DMD was 2.9 ± 1.1 months in group 1 vs. 6.8 ± 1.5 months in group 2 (p = 0.002). Conclusion although a shortening in time of diagnosis was described, a trend to increase the time to initiate a DMD was noted in group 2.

The use of non-thermal plasma (NTP) generators in air processing systems and their duct networks to improve indoor air quality (IAQ) has grown considerably in recent years. This paper reviews the advantages and disadvantages of NTP generators for IAQ improvement in biological, chemical and particulate pollutant terms. Also, it assesses and compares the ability of a multipin corona discharge (MPCD) and a dielectric barrier discharge (DBD) generator to reduce the concentration of fine particulate matter (PM2.5) in recycled, unfiltered air in a refrigeration chamber. The MPCD generator was found to have a higher PM2.5 removal efficiency; also, it was faster in removing pollutants, used less energy, and produced much less ozone. The fact that the MPCD generator performed better was seemingly the result of its increased ion production mainly. NTP generators, however, cannot match air filtration media purifiers in this respect as the latter are much more effective in removing particles. Besides, NTP-based air purifying technology continues to be subject to a major drawback, namely: the formation of ozone as a by-product. In any case, the ozone generation was uncorrelated to ion emission when using different technologies.

Due to the high spread of the COVID-19 virus, several diagnosis support systems are being developed in order to detect the disease in a faster and accurate way. In this paper, a stacking method for Computed Tomography (CT) scans has been implemented for the pre-processing step. The method combines both slice normalization and lung segmentation in a single output image using RGB color channels, providing more information from the input slices to the CNN models. The binary classification step starts with a slice-level prediction, which applies fine-tuning to the whole model and dense layers are changed by a custom scheme to improve the performance. Then, a patient-level prediction is performed by fixing a threshold percentage of COVID positive slices that allows to make the final prediction, classifying patients as COVID or NORMAL. The accuracy and metrics obtained show the robustness of the presented method in comparison to using the normalised slices or the masks independently. Given the results obtained, the proposed method can accurately detect the COVID-19 disease and the fusion of information improves the results obtained.

State of the art classifiers split Alzheimer’s disease progression into a limited number of stages and use a comparatively small database. For the best treatment, it is desirable to have the highest resolution from the progression of the disease. This paper proposes a reliable deep convolutional neural network for the classification of six different Alzheimer’s disease stages based on Magnetic Resonance Imaging (MRI). The peculiarity of this paper is the introduction of a new, sixth, disease stage, and the large amount of data that has been taken into account. Additionally, not only the testing accuracy is analyzed, but also the robustness of the classifier to have feedback on how certain the neural network makes its predictions.

Lung cancer is one of the most frequent cancer types, and one among those causing more deceases worldwide. Nowadays, in order to improve the diagnosis of cancer more screenings are performed to the same patient and various biological sources are being gathered. Fusing the information provided by these sources can lead to a more robust diagnosis, which can improve the prognosis of the patient. In this work, a comparison of fusion methodologies (early and intermediate) using RNA-Seq and Copy Number Variation data for Non-Small-Cell Lung Cancer classification is performed. We found that great results can be attained using both fusion methodologies, with an AUC of 0.984 for the early fusion and 0.989 for the intermediate fusion, improving those obtained by each source of information independently (0.978 RNA-Seq and 0.910 Copy Number Variation). This work shows that fusion methodologies can enhance the classification of non-small-cell lung cancer, and that these methodologies can be promising for the diagnosis of other cancer types.

Background: methodological challenges limit the use of brain atrophy and lesion burden measures in the followup of multiple sclerosis (MS) patients on clinical routine datasets. Objective: to determine the feasibility of T2-FLAIR-only measures of lateral ventricular volume (LVV) and salient central lesion volume (SCLV), as markers of disability progression (DP) in MS. Methods: a total of 3,228 MS patients from 9 MSBase centers in 5 countries were enrolled. Of those, 2,875 (218 with clinically isolated syndrome, 2,231 with relapsing-remitting and 426 with progressive disease subtype) fulfilled inclusion and exclusion criteria. Patients were scanned on either 1.5 T or 3 T MRI scanners, and 5,750 brain scans were collected at index and on average after 42.3 months at post-index. Demographic and clinical data were collected from the MSBase registry. LVV and SCLV were measured on clinical routine T2-FLAIR images. Results: longitudinal LVV and SCLV analyses were successful in 96% of the scans. 57% of patients had scanner related changes over the follow-up. After correcting for age, sex, disease duration, disability, disease-modifying therapy and LVV at index, and follow-up time, MS patients with DP (n = 671) had significantly greater absolute LVV change compared to stable (n = 1,501) or disability improved (DI, n = 248) MS patients (2.0 mL vs. 1.4 mL vs. 1.1 mL, respectively, ANCOVA p < 0.001, post-hoc pair-wise DP vs. Stable p = 0.003; and DP vs. DI, p = 0.002). Similar ANCOVA model was also significant for SCLV (p = 0.03). Conclusions: LVV-based atrophy and SCLV-based lesion outcomes are feasible on clinically acquired T2-FLAIR scans in a multicenter fashion and are associated with DP over mid-term., Novartis; Genzyme-Sanofi; Biogen; Merck; Genentech; Abbvie; Bayer AG; Celgene/ BMS; Mallinckrodt Pharmaceuticals, Inc.; WebMD Global; Teva; BioCSL; Almirall; Roche; Generica; Deva; Nerve Research Foundation; Multiple Sclerosis Research Australia; Keystone Heart; Bristol Myers Squibb; EMD Serono; V-WAVE Medical; Mapi Pharma; Protembis

This work was funded by the Spanish Ministry of Sciences, Innovation and Universities under Project RTI2018-101674-B-I00 titled "Computer Architectures and Machine Learningbased solutions for complex challenges in Bioinformatics, Biotechnology and Biomedicine", in collaboration with the Government of Andalusia under Postdoctoral Grant P12TIC2082. The funders had no role in study design, datacollection and analysis, decision to publish, or preparation of this manuscript. The results published here are in whole or part based upon data generated by the TCGA Research Network: https:// www.cancer. gov/tcga., KnowSeq R/Bioc package is designed as a powerful, scalable and modular software focused on automatizing and assembling renowned bioinformatic tools with new features and functionalities. It comprises a unified environment to perform complex gene expression analyses, covering all the needed processing steps to identify a gene signature for a specific disease to gather understandable knowledge. This process may be initiated from raw files either available at well-known platforms or provided by the users themselves, and in either case coming from different information sources and different Transcriptomic technologies. The pipeline makes use of a set of advanced algorithms, including the adaptation of a novel procedure for the selection of the most representative genes in a given multiclass problem. Similarly, an intelligent system able to classify new patients, providing the user the opportunity to choose one among a number of well-known and widespread classification and feature selection methods in Bioinformatics, is embedded. Furthermore, KnowSeq is engineered to automatically develop a complete and detailed HTML report of the whole process which is also modular and scalable. Biclass breast cancer and multiclass lung cancer study cases were addressed to rigorously assess the usability and efficiency of KnowSeq. The models built by using the Differential Expressed Genes achieved from both experiments reach high classification rates. Furthermore, biological knowledge was extracted in terms of Gene Ontologies, Pathways and related diseases with the aim of helping the expert in the decision-making process. KnowSeq is available at Bioconductor (https://bioconductor.org/packages/KnowSeq), GitHub (https://github.com/CasedUgr/KnowSeq) and Docker (https://hub.docker.com/r/casedugr/knowseq)., Spanish Ministry of Sciences, Innovation and Universities RTI2018-101674-B-I00, Government of Andalusia P12TIC2082

Due to the urgency of the COVID pandemic, it is necessary to develop new and quick methods to detect the infection and stop the spread of the disease. In this work we compare a simple Deep Learning (DL) model with an ensemble model in the task of COVID detection in X-Ray images. For the simple model, we have used only frontal DX X-Ray images while, for the ensemble model, we have used frontal DX and CR X-Ray images, as well as lateral DX and CR X-Ray images. In the ensemble model, the features of the four images are combined to make a final prediction and, since not every patient possess all types of images, the model is also robust against missing information, which is crucial in these types of models. Although the dataset used is very noisy, the presented system has shown the desired robustness and offers relevant results, showing that ensemble models can generalize better over the data, which leads to a higher accuracy. Finally, we share our conclusions and discuss future work where we want to try using a similar methodology .

‘KnowSeq’ R Package includes all the essential tools to carry out transcriptomic analysis, providing intuitive functions to build efficient and robust pipelines. In this paper, its capacities are demonstrated in a practical COVID-19 biomarkers detection problem using RNA-Sequencing data. Through Machine Learning techniques such as feature selection and supervised classification models, a clinical decision system for COVID-19 was developed using four genes proposed as COVID-19 signature: OAS3, CXCL9, IFITM1 and IFIT3. These four genes are highly related to different processes that affect the immune system behaviour and its response when facing viruses such as SARS-CoV-2. The final model reaches an accuracy over 97% when predicting over unseen samples.

Nº Artículo: 33 This article introduces an innovative application of Visual Basic for Applications (VBA) (Visual Basic macro language) developed in CATIA (Computer-Aided Three-Dimensional Interactive Application), computer-aided manufacturing and engineering design software. Said application enables the three-dimensional (3D) representation and development to be obtained on a plane of the surfaces of cylindrical and conical elbows utilised to join two conduits, since CATIA lacks tools for the design of elements of metal fabrication. The application permits the geometric and dimensional parameters necessary for the creation and development of the analysed elbows to be introduced via a keyboard. Once these values have been entered and it has been verified that the design of the elbow is possible, then the application is programmed within the CATIA “Wireframe and Surface Design” module to obtain the 3D representation of said elbows, and the development of their surface is projected in the CATIA “Drafting” module. Consequently, the incorporation of this tool into CATIA software could increase technical-design productivity by eliminating certain intermediate operations, such as symmetry, and through improving the geometry training of less skilled users.

Introduction: The outbreak of the new coronavirus (COVID-19) was declaredas a pandemic by the World Health Organization in March 2020. TheArgentinian government adopted a preventive social isolation and lockdownstrategy as an exceptional measure in this critical world context. This lockdownstrategy has kept a large number of people in isolation and affectedmany aspects of people?s lives. Objective: To describe the physical and mentalhealth status and possible changes in hygienic, nutritional and, daily habitsduring quarantine in the COVID-19 pandemic. Materials and Method: Anonline anonymous survey was sent to the general population of Buenos Airescity, 434 people answered the questionnaire. Results: Fifty-one percent ofrespondents were between 40 and 70 years old. Most respondents were female(75.8%) and had higher education (62.2%). Thirty point eight percent had apre-existing disease and in 50.7% of these cases, the usual symptoms experiencedby respondents remained unchanged. The onsets of anxiety (38.2%),depression symptoms (27.9%), sleep disorders (20.5%), and irritability(27.2%) were reported during the isolation period. Also, changes in eatinghabits (55.5%) were reported. Significant improvement was reported in personalhygiene (80.2%) and home cleaning (81.3%) habits. It was also observedthat despite the isolation some people continued doing physical activity.Conclusions: Respondents did not report significant changes in the symptomsof their preexisting diseases and had a positive mindset towards personalhygiene and home cleaning. Also, reported continuity in physical activity during isolation. However, the onset of psychiatric symptoms such as anxiety, depression, irritability and sleep problems, and, changes in eating habits were observed during the quarantine. Fil: Dillon, Carol. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina. Universidad de Palermo; Argentina Fil: Pérez Leguizamón, Patricio Rosendo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina Fil: Castro, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina Fil: Guelar, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina Fil: Garcia, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina Fil: Feldman, Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina Fil: Leis, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina Fil: Romano, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina Fil: Peralta, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina Fil: Rojas, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina Fil: Maggi, Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina Fil: Viaggio, María Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina

Over the past decade, numerous disease modifying drugs (DMDs) for relapsing- remitting multiple sclerosis (RRMS) have been approved in Argentina. The use of oral DMDs (oDMDs) has increased in recent years, although real-life data in our region is limited. We aimed to describe the tendency in the use of oDMDs (as first treatment option or after switch) in relationship with their approval in Argentina.A retrospective study in a cohort of MS patients from five Argentinian MS centers was conducted. Regarding the availability of different oDMDs in Argentina, we define three periods (P1-3): P1: 2012 - 2014; P2: 2015 - 2017 and P3: 2018 - 2020. An analysis was performed comparing between these three periods to assess the tendency for oDMDs use over time.The most frequently prescribed treatment as first DMD was: interferon beta 1a (40%) in P1, fingolimod (37.3%) in P2 and also fingolimod (35%) in P3. We found an increase in the use of oDMTs as initial treatment over time (P1: 17.7%, P2: 63.9% and P3: 65.0%; Chi-square = 41.9 p0.01). We also found a tendency to increase the use of oDMTs after a first switch (P1: 45.5%, P2: 60.1% and P3 78.3%). Multivariate analysis showed that disease evolution (OR=1.06, p=0.04), and year of treatment initiation (OR=1.01 p0.01) were independently associated with choice of oDMTs.This study identified an increasing tendency for the use of oDMDs as initial treatment of RMS in relationship with their approval in Argentina.

Technological advances and greater availability of magnetic resonance imaging have prompted an increment on incidental and unexpected findings within the central nervous system. The concept of radiologically isolated syndrome characterizes a group of subjects with images suggestive of demyelinating disease in the absence of a clinical episode compatible with multiple sclerosis. Since the description of this entity, many questions have arisen; some have received responses but others remain unanswered. A panel of experts met with the objective of performing a critical review of the currently available evidence. Definition, prevalence, biological bases, published evidence, and implications on patient management were reviewed. Thirty to 50% of subjects with radiologically isolated syndrome will progress to multiple sclerosis in 5 years. Male sex, age < 37 years old, and spinal lesions increase the risk. These subjects should be evaluated by a multiple sclerosis specialist, carefully excluding alternative diagnosis. An initial evaluation should include a brain and complete spine magnetic resonance, visual evoked potentials, and identification of oligoclonal bands in cerebrospinal fluid. Disease-modifying therapies could be considered when oligoclonal bands or radiological progression is present. At present time, radiologically isolated syndrome cannot be considered a part of the multiple sclerosis spectrum. However, a proportion of patients may evolve to multiple sclerosis, meaning it represents much more than just a radiological finding.

Background Few studies regarding MRI-defined acute optic nerve lesions (aONL) in patients with first-ever neuromyelitis optica spectrum disorder (NMOSD)-related optic neuritis (ON) have been reported worldwide and none of them was conducted in Latin America (LATAM). Therefore, we aimed to assess the frequency of aONL at disease onset using conventional brain MRI in LATAM. Methods We reviewed the medical records and brain MRIs (≤30 days from ON onset) of patients with ON as first lifetime NMOSD attack. Patients from Argentina (n=48), Ecuador (n=24), Brazil (n=22), Venezuela (n=10) and Mexico (n=8) were included, and further divided into two subgroups according to either presence (P-MRI) or absence (A-MRI) of aONL (T2 hyperintensity and/or contrast enhancement). Clinical, paraclinical, imaging and prognostic data were compared. Results A total of 112 patients were included and aONL were found in 86 (76.7%) at disease onset. Aquaporin-4 antibodies were detected in 69.6%. Non-Caucasian patients comprised 59.8% of the total cohort. In P-MRI, conventional brain MRI showed isolated or combined unilateral (54.4%, [8.5% of these aONL were associated with chiasmatic lesions]) and bilateral (46.6%, [35.9% of these aONL were associated with chiasmatic lesions]) lesions. Thus, 100% of chiasmatic lesions were associated with unilateral or bilateral lesions. No statistically significant differences were found in age, gender, ethnicity, clinical course, mean follow-up time, disability, and spinal cord MRI findings. However, rituximab use was higher in P-MRI than in A-MRI (p=0.006). Conclusions More than three quarters of LATAM patients with first-ever NMOSD-related ON have aONL detected by brain MRI. Unilateral lesions were the most common finding. Further studies including different ethnicities are needed to assess the generalizability of our results.

Background: Despite the abundance of information concerning ocrelizumab in phase III clinical trials, there is scarce evidence regarding real-world patient profiles. Objective: The aim of this study was to investigate patient profiles, effectiveness and persistence with treatment among patients who used ocrelizumab for treatment of multiple sclerosis in Latin America. Methods: This was a retrospective multicenter study in Argentina, Chile and Mexico. Medical record databases on patients who received ocrelizumab were analyzed. Demographic and clinical variables were described, along with effectiveness outcomes, which included the proportions of patients free from clinical relapses, from disability progression and from new or enlarging T2 or T1 gadolinium-enhancing lesions, on annual magnetic resonance imaging. Results: A total of 81 patients were included. The most frequent phenotype was relapsing-remitting MS, in 64.2% of the patients. The mean age at study entry was 41.3 ± 12.0 years and 51.8% were women. A total of 38% had had relapse activity during the 12 months before starting on ocrelizumab, with a mean relapse rate of 1.3 ± 0.6 during that period. 75% were free from clinical relapses and 91% were free from gadolinium-enhancing lesions in the relapsing-remitting course. Ocrelizumab discontinuation during the first 12 months was observed in three patients (3.7%). The mean persistence observed during the first-year follow-up was 338 ± 24 days. Conclusions: Our study is in line with previous randomized clinical trials and recent real-world studies describing patient profiles, effectiveness and persistence regarding ocrelizumab treatment in multiple sclerosis patients in Latin America. RESUMEN Introducción: A pesar de la abundante información sobre ocrelizumab proveniente de los ensayos clínicos de fase III, todavía se tiene poca evidencia sobre la efectividad y el perfil de pacientes provenientes de la vida real. Objetivo: Evaluar el perfil clínico y demográfico, la efectividad y la persistencia al tratamiento en pacientes que usaron el ocrelizumab para el tratamiento de esclerosis múltiple (EM) en Latinoamérica. Métodos: Estudio retrospectivo multicéntrico en Argentina, Chile y México. Se analizaron los datos de los pacientes que recibieron ocrelizumab. Se describieron las variables demográficas y clínicas, así como los resultados de efectividad que incluyeron la proporción de pacientes libres de recaídas clínicas, libres de progresión de la discapacidad, libres de nuevas lesiones en la secuencia T2 o T1 con gadolinio durante el seguimiento. Resultados: Se incluyeron 81 pacientes. El fenotipo más frecuente fue EM remitente recurrente (EMRR) en el 64,2% de los pacientes. La edad media fue de 41.3±12 años, y el 51,8% eran mujeres. Un total de 38% tuvo recaídas durante los 12 meses previos al inicio de ocrelizumab, con una tasa anualizada de recaídas media de 1.3±0.6 durante ese período. En el seguimiento a 12 meses, el 75% estuvo libre de recaídas clínicas y el 91%, libre de nuevas lesiones en RM. Tres pacientes interrumpieron el tratamiento durante el seguimiento (3,7%). La persistencia al tratamiento observada durante el primer año de seguimiento fue de 338±24 días. Conclusión: Nuestro estudio está en línea con los datos provenientes de ensayos clínicos aleatorizados previos y estudios recientes del mundo real que describen la efectividad de los perfiles de pacientes y la persistencia al tratamiento con ocrelizumab en pacientes con EM en Latinoamérica.

This article presents evidence of the convenience of implementing the geometric places of the plane into commercial computer-aided design (CAD) software as auxiliary tools in the computer-aided sketching process. Additionally, the research considers the possibility of adding several intuitive spatial geometric places to improve the efficiency of the three-dimensional geometric design. For demonstrative purposes, four examples are presented. A two-dimensional figure positioned on the flat face of an object shows the significant improvement over tools currently available in commercial CAD software, both vector and parametric: it is more intuitive and does not require the designer to execute as many operations. Two more complex three-dimensional examples are presented to show how the use of spatial geometric places, implemented as CAD software functions, would be an effective and highly intuitive tool. Using these functions produces auxiliary curved surfaces with points whose notable features are a significant innovation. A final example provided solves a geometric place problem using own software designed for this purpose. The proposal to incorporate geometric places into CAD software would lead to a significant improvement in the field of computational geometry. Consequently, the incorporation of geometric places into CAD software could increase technical-design productivity by eliminating some intermediate operations, such as symmetry, among others, and improving the geometry training of less skilled users.

Technical historical heritage and/or industrial heritage are manifestations of heritage that acquire greater relevance every day, since their study and analysis provide a global vision of their impact on the development of the societies and, also, because they favor the understanding of the technological evolution of these societies. The fields of action are very broad, both from the point of view of engineering and its different disciplines as well as from architecture. This Special Issue shows the reader some of the tools currently available to value this heritage and promote its dissemination, such as geometric modeling, computer-aided design, computer-aided engineering, and the study of industrial heritage from a global perspective.

The main objective is to perform a quantitative and qualitative analysis from the institutional point of view of the related research on Building Information Modeling (BIM) collected in the Web of Science Core Collection during the period 2003- 2017. For this, all documents of the type ‘article’ or ‘review’ were reviewed and several bibliometric indicators analyzed. Similarly, the international dissemination of the research of the 16 most productive countries was analyzed, indicating the publication journals of each country and concluding that the main journals. USA is the most productive country although with a relative impact factor slightly higher than average due to the dispersion of its publications in journals of medium or low impact. It also shows how Curtin University (Australia) and the Georgia Institute of Technology (USA) have been the most productive and high impact institutions, although the outstanding rise of Hong Kong Polytechnic University is noted.

This article shows the geometric modeling and virtual reconstruction of the optical telegraph by Agust&iacute, n de Betancourt and Abraham Louis Breguet developed at the end of the 18th century. Autodesk Inventor Professional software has been used to obtain the three-dimensional (3D) model of this historical invention and its geometric documentation. The material for the research is available on the website of the Betancourt Project of the Canary Orotava Foundation for the History of Science. Thanks to the three-dimensional modeling performed, it has been possible to explain in detail both its operation and the assembly system of this invention in a coherent way. After carrying out its 3D modeling and functional analysis, it was discovered that the transmissions in the telegraph were not performed by hemp ropes but rather by metal chains with flat links, considerably reducing possible error. Similarly, it has also been found that the use of the gimbal joint facilitated the adaptability of the invention to geographical areas where there was a physical impediment to the alignment of telegraph stations. In addition, it was not now necessary for the telescope frames to be located parallel to the mast frame (frame of the indicator arrow) and therefore they could work in different planes.

Stroke is the second leading cause of mortality and the major cause of adult physical disability worldwide. The currently available treatment to recanalize the blood flow in acute ischemic stroke is intravenous administration of tissue plasminogen activator (t-PA) and endovascular treatment. Nevertheless, those treatments have the disadvantage that reperfusion leads to a highly harmful reactive oxygen species (ROS) production, generating oxidative stress (OS), which is responsible for most of the ischemia-reperfusion injury and thus causing brain tissue damage. In addition, OS can lead brain cells to apoptosis, autophagy and necrosis. The aims of this review are to provide an updated overview of the role of OS in brain IRI, providing some bases for therapeutic interventions based on counteracting the OS-related mechanism of injury and thus suggesting novel possible strategies in the prevention of IRI after stroke.

This article presents both the three-dimensional modelling of the isochronous pendulum clock and the simulation of its movement, as designed by the Dutch physicist, mathematician, and astronomer Christiaan Huygens, and published in 1673. This invention was chosen for this research not only due to the major technological advance that it represented as the first reliable meter of time, but also for its historical interest, since this timepiece embodied the theory of pendular movement enunciated by Huygens, which remains in force today. This 3D modelling is based on the information provided in the only plan of assembly found as an illustration in the book Horologium Oscillatorium, whereby each of its pieces has been sized and modelled, its final assembly has been carried out, and its operation has been correctly verified by means of CATIA V5 software. Likewise, the kinematic simulation of the pendulum has been carried out, following the approximation of the string by a simple chain of seven links as a composite pendulum. The results have demonstrated the exactitude of the clock.

This paper shows the geometric modeling and virtual reconstruction of the inclined plane rosary pump included in the work ‘Elements of Mathematics’ by Benito Bails of 1790, specifically in Volume X, Tome IX, Part II on Hydraulic Architecture. The software Autodesk Inventor Professional has been used, which has allowed us to obtain its geometric documentation (plan of the ensemble, isometric and exploded views and 3D digital restitution). The material used in this research has been downloaded from the Biblioteca Digital Hispanica of the National Library of Spain. However, and as a drawback, it is necessary to indicate that the only available sheet does not have a graphic scale, nor does there exist expressly in the specification any reference measure that would allow obtaining said graphic scale, which is insufficient for obtaining a reliable 3D CAD model. For this reason, a graphic scale has been adopted from an estimated dimension of a known element (yoke), as well as a series of geometric, dimensional and movement constraints (degrees of freedom) in order to obtain a coherent model.

We aimed to assess the clinical, paraclinical, imaging and prognostic features of patients with late-onset neuromyelitis optica spectrum disorder (LO-NMOSD; ≥ 50 years at disease onset) LO-NMOSD, compared with early onset-NMOSD (EO-NMOSD, ≤ 49 years at disease onset), in Latin American (LATAM). We retrospectively reviewed the medical records of patients with NMOSD, as defined using the 2015 validated diagnostic criteria. We included patients from Argentina, Brazil and Venezuela. They were divided into: LO-NMOSD and EO-NMOSD and comparison among the groups were performed. Among these 140 NMOSD patients, 24 (17.1%) were LO-NMOSD; 64% were positive for aquaporin-4 antibodies; and 41.5% of this population cohort was non-Caucasian. Severe disability [expanded disability status scale (EDSS) ≥ 6] at the last follow-up and presence of comorbidities were significantly associated with LO-NMOSD, compared with EO-NMOSD. LO-NMOSD patients had a shorter median time to EDSS ≥ 4 than EO-NMOSD patients (46 vs. 60 months; log-rank test p = 0.0006). Furthermore, we observed a positive correlation between age at onset and EDSS score at the last follow-up (Spearman r = 0.34, p

We want to thank the great work done by the reviewers of each of the papers, together with the great interest shown by the editorial of BMC Bioinformatics in IWBBIO Conference. Special thanks to D. Omar El Bakry for his interest and great help to make this Special Issue. Thank the Ministry of Spain for the economic resources within the project with reference RTI2018-101674-B-I00., In the current supplement, we are proud to present seventeen relevant contributions from the 6th International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO 2018), which was held during April 25-27, 2018 in Granada (Spain). These contributions have been chosen because of their quality and the importance of their findings., This research has been partially supported by the proyects with reference RTI2018-101674-B-I00 (Ministry of Spain) and B-TIC-414-UGR18 (FEDER, Junta Andalucia and UGR).