Surface-Based tools for Characterizing the Human Brain Cortical Morphology

Tesis por compendio de publicacionesThe cortex of the human brain is highly convoluted. These characteristic convolutions present advantages over lissencephalic brains. For instance, gyrification allows an expansion of cortical surface area without significantly increasing the cranial volume, thus facilitating the pass of the head through the birth channel. Studying the human brain’s cortical morphology and the processes leading to the cortical folds has been critical for an increased understanding of the pathological processes driving psychiatric disorders such as schizophrenia, bipolar disorders, autism, or major depression. Furthermore, charting the normal developmental changes in cortical morphology during adolescence or aging can be of great importance for detecting deviances that may be precursors for pathology. However, the exact mechanisms that push cortical folding remain largely unknown. The accurate characterization of the neurodevelopment processes is challenging. Multiple mechanisms co-occur at a molecular or cellular level and can only be studied through the analysis of ex-vivo samples, usually of animal models. Magnetic Resonance Imaging can partially fill the breach, allowing the portrayal of the macroscopic processes surfacing on in-vivo samples. Different metrics have been defined to measure cortical structure to describe the brain’s morphological changes and infer the associated microstructural events. Metrics such as cortical thickness, surface area, or cortical volume help establish a relation between the measured voxels on a magnetic resonance image and the underlying biological processes. However, the existing methods present limitations or room for improvement. Methods extracting the lines representing the gyral and sulcal morphology tend to over- or underestimate the total length. These lines can provide important information about how sulcal and gyral regions function differently due to their distinctive ontogenesis. Nevertheless, some methods label every small fold on the cortical surface as a sulcal fundus, thus losing the perspective of lines that travel through the deeper zones of a sulcal basin. On the other hand, some methods are too restrictive, labeling sulcal fundi only for a bunch of primary folds. To overcome this issue, we have proposed a Laplacian-collapse-based algorithm that can delineate the lines traversing the top regions of the gyri and the fundi of the sulci avoiding anastomotic sulci. For this, the cortex, represented as a 3D surface, is segmented into gyral and sulcal surfaces attending to the curvature and depth at every point of the mesh. Each resulting surface is spatially filtered, smoothing the boundaries. Then, a Laplacian-collapse-based algorithm is applied to obtain a thinned representation of the morphology of each structure. These thin curves are processed to detect where the extremities or endpoints lie. Finally, sulcal fundi and gyral crown lines are obtained by eroding the surfaces while preserving the structure topology and connectivity between the endpoints. The assessment of the presented algorithm showed that the labeled sulcal lines were close to the proposed ground truth length values while crossing through the deeper (and more curved) regions. The tool also obtained reproducibility scores better or similar to those of previous algorithms. A second limitation of the existing metrics concerns the measurement of sulcal width. This metric, understood as the physical distance between the points on opposite sulcal banks, can come in handy in detecting cortical flattening or complementing the information provided by cortical thickness, gyrification index, or such features. Nevertheless, existing methods only provided averaged measurements for different predefined sulcal regions, greatly restricting the possibilities of sulcal width and ignoring the intra-region variability. Regarding this, we developed a method that estimates the distance from each sulcal point in the cortex to its corresponding opposite, thus providing a per-vertex map of the physical sulcal distances. For this, the cortical surface is sampled at different depth levels, detecting the points where the sulcal banks change. The points corresponding to each sulcal wall are matched with the closest point on a different one. The distance between those points is the sulcal width. The algorithm was validated against a simulated sulcus that resembles a simple fold. Then the tool was used on a real dataset and compared against two widely-used sulcal width estimation methods, averaging the proposed algorithm’s values into the same region definition those reference tools use. The resulting values were similar for the proposed and the reference methods, thus demonstrating the algorithm’s accuracy. Finally, both algorithms were tested on a real aging population dataset to prove the methods’ potential in a use-case scenario. The main idea was to elucidate fine-grained morphological changes in the human cortex with aging by conducting three analyses: a comparison of the age-dependencies of cortical thickness in gyral and sulcal lines, an analysis of how the sulcal and gyral length changes with age, and a vertex-wise study of sulcal width and cortical thickness. These analyses showed a general flattening of the cortex with aging, with interesting findings such as a differential age-dependency of thickness thinning in the sulcal and gyral regions. By demonstrating that our method can detect this difference, our results can pave the way for future in vivo studies focusing on macro- and microscopic changes specific to gyri or sulci. Our method can generate new brain-based biomarkers specific to sulci and gyri, and these can be used on large samples to establish normative models to which patients can be compared. In parallel, the vertex-wise analyses show that sulcal width is very sensitive to changes during aging, independent of cortical thickness. This corroborates the concept of sulcal width as a metric that explains, in the least, the unique variance of morphology not fully captured by existing metrics. Our method allows for sulcal width vertex-wise analyses that were not possible previously, potentially changing our understanding of how changes in sulcal width shape cortical morphology. In conclusion, this thesis presents two new tools, open source and publicly available, for estimating cortical surface-based morphometrics. The methods have been validated and assessed against existing algorithms. They have also been tested on a real dataset, providing new, exciting insights into cortical morphology and showing their potential for defining innovative biomarkers.Programa de Doctorado en Ciencia y Tecnología Biomédica por la Universidad Carlos III de MadridPresidente: Juan Domingo Gispert López.- Secretario: Norberto Malpica González de Vega.- Vocal: Gemma Cristina Monté Rubi

Characterizing zebra crossing zones using LiDAR data

Light detection and ranging (LiDAR) scanning in urban environments leads to accurate and dense three-dimensional point clouds where the different elements in the scene can be precisely characterized. In this paper, two LiDAR-based algorithms that complement each other are proposed. The first one is a novel profiling method robust to noise and obstacles. It accurately characterizes the curvature, the slope, the height of the sidewalks, obstacles, and defects such as potholes. It was effective for 48 of 49 detected zebra crossings, even in the presence of pedestrians or vehicles in the crossing zone. The second one is a detailed quantitative summary of the state of the zebra crossing. It contains information about the location, the geometry, and the road marking. Coarse grain statistics are more prone to obstacle-related errors and are only fully reliable for 18 zebra crossings free from significant obstacles. However, all the anomalous statistics can be analyzed by looking at the associated profiles. The results can help in the maintenance of urban roads. More specifically, they can be used to improve the quality and safety of pedestrian routesConsellería de Cultura, Educación e Ordenación Universitaria, Grant/Award Numbers: accreditation 2019-2022 ED431G-2019/04, 2022-2024, ED431C2022/16, ED481A-2020/231; European Regional Development Fund (ERDF); CiTIUS-Research Center in Intelligent Technologies of the University of Santiago de Compostela as a Research Center of the Galician University System; Ministry of Economy and Competitiveness, Government of Spain, Grant/Award Number: PID2019-104834GB-I00; National Department of Traffic (DGT) through the project Analysis of Indicators Big-Geodata on Urban Roads for the Dynamic Design of Safe School Roads, Grant/Award Number: SPIP2017-02340S

Multi-parameter flow cytometry immunophenotyping distinguishes different stages of tuberculosis infection

Objectives: To identify new potential host biomarkers in blood to discriminate between active TB patients, uninfected (NoTBI) and latently infected contacts (LTBI). Methods: A blood cell count was performed to study parent leukocyte populations. Peripheral blood mononuclear cells (PBMCs) were isolated and a multi-parameter flow cytometry assay was conducted to study the distribution of basal and Mycobacterium tuberculosis (Mtb)-stimulated lymphocytes. Differences between groups and the area under the ROC curve (AUC) were investigated to assess the diagnostic accuracy. Results: Active TB patients presented higher Monocyte-to-lymphocyte and Neutrophil-to-lymphocyte ratios than LTBI and NoTBI contacts (p0.8). Lymphocyte subsets with differences (p >0.05; AUC >0.7) between active TB and both contact groups include the basal distribution of Th1/Th2 ratio, Th1-Th17, CD4+ Central Memory (TCM) or MAIT cells. Expression of CD154 is increased in Mtb-activated CD4+ TCM and Effector Memory T cells in active TB and LTBI compared to NoTBI. In CD4+T cells, expression of CD154 showed a higher accuracy than IFNγ to discriminate Mtb-specific activation. Conclusions: We identified different cell subsets with potential use in tuberculosis diagnosis. Among them, distribution of CD4 TCM cells and their expression of CD154 after Mtb-activation are the most promising candidates.Xunta de Galicia | Ref. ED431C 2016/04

Late presentation of human T-lymphotropic virus type 1 infection in Spain reflects suboptimal testing strategies

Diagnosis; Myelopathy; Sexually transmitted infectionsDiagnóstico; Mielopatía; Infecciones de transmisión sexualDiagnòstic; Mielopatia; Infeccions de transmissió sexualObjectives Although only 10% of persons infected with human T-lymphotropic virus type 1 (HTLV-1) may develop virus-associated illnesses over their lifetime, missing the earlier diagnosis of asymptomatic carriers frequently leads to late presentation. Methods A nationwide HTLV-1 register was created in Spain in 1989. We examined the main demographics and clinical features at the time of the first diagnosis for more than three decades. Results A total of 428 individuals infected with HTLV-1 had been reported in Spain until the end of 2021. Up to 96 (22%) individuals presented clinically with HTLV-1-associated conditions, including subacute myelopathy (57%), T-cell lymphoma (34%), or Strongyloides stercoralis infestation (8%). Since 2008, HTLV-1 diagnosis has been made at blood banks (44%) or clinics (56%). Native Spaniards and Sub-Saharan Africans are overrepresented among patients presenting with HTLV-1-associated illnesses suggesting that poor epidemiological and/or clinical suspicion, which led to the late presentation are more frequent in them than carriers from Latin America (LATAM) (31.7% vs 20.4%, respectively; P = 0.015). Conclusion HTLV-1 infection in Spain is frequently diagnosed in patients presenting with characteristic illnesses. Although screening in blood banks mostly identifies asymptomatic carriers from LATAM, a disproportionately high number of Spaniards and Africans are diagnosed too late at the time of clinical manifestations. Expanding testing to all pregnant women and clinics for sexually transmitted infections could help to unveil HTLV-1 asymptomatic carriers.This work was supported in part by grants from FIS-ISCIII PI-21/1717 and Fundación Mutua Madrileña AP-174112020

Correlation of social networks with traditional metrics of impact on scientific journals in nursing

Q3Different bibliometric indexes allow researchers to evaluate the impact of scientific journals based on the number of citations received by their publications. However, the correlation of these indexes with alternative metrics that evaluate the presence of journals on social networks has not been evaluated in nursing journals. The objective of this study was to evaluate the correlation between the SCImago Journal Ranking Indicator (SJR) and alternative metrics of presence in four social networks (Twitter, Facebook, YouTube, Instagram) on indexed nursing journals. A correlation study was conducted in March 2019 through which the nursing journals included in the SJR were identified. Out of a total of 131 journals, 67 were excluded because they were active on social networks that were not their own. 64 were included for analysis. The most frequently used social networks were Twitter (75%) and Facebook (75%). The journals with presence on social networks had higher values for H Index (36.5 vs 12.0, p = 0.00037) and SJR (0.452 vs 0.268, p = 0.0069), and a higher number of publications (≥ 500 publications in 3 years, p = 0.03 ) than those without social networks. The correlation between the SJR and the number of followers on Twitter (r: - 0.067) and the number of followers on Facebook (- 0.18) were poor and in some cases negative. We concluded that the use of social networks as a means of dissemination and interaction by nursing journals is high, being used as a strategy of visibility and dissemination of journal contents.Revista Internacional - Indexad

ABLE: Automated Brain Lines Extraction Based on Laplacian Surface Collapse.

The archetypical folded shape of the human cortex has been a long-standing topic for neuroscientific research. Nevertheless, the accurate neuroanatomical segmentation of sulci remains a challenge. Part of the problem is the uncertainty of where a sulcus transitions into a gyrus and vice versa. This problem can be avoided by focusing on sulcal fundi and gyral crowns, which represent the topological opposites of cortical folding. We present Automated Brain Lines Extraction (ABLE), a method based on Laplacian surface collapse to reliably segment sulcal fundi and gyral crown lines. ABLE is built to work on standard FreeSurfer outputs and eludes the delineation of anastomotic sulci while maintaining sulcal fundi lines that traverse the regions with the highest depth and curvature. First, it segments the cortex into gyral and sulcal surfaces; then, each surface is spatially filtered. A Laplacian-collapse-based algorithm is applied to obtain a thinned representation of the surfaces. This surface is then used for careful detection of the endpoints of the lines. Finally, sulcal fundi and gyral crown lines are obtained by eroding the surfaces while preserving the connectivity between the endpoints. The method is validated by comparing ABLE with three other sulcal extraction methods using the Human Connectome Project (HCP) test-retest database to assess the reproducibility of the different tools. The results confirm ABLE as a reliable method for obtaining sulcal lines with an accurate representation of the sulcal topology while ignoring anastomotic branches and the overestimation of the sulcal fundi lines. ABLE is publicly available via https://github.com/HGGM-LIM/ABLE .This work was supported by the project exAScale ProgramIng models for extreme Data procEssing (ASPIDE), that has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 801091. This work has received funding from “la Caixa” Foundation under the project code LCF/PR/HR19/52160001. Susanna Carmona funded by Instituto de Salud Carlos III, co-funded by European Social Fund “Investing in your future” (Miguel Servet Type I research contract CP16/00096). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Yasser Alemán-Gómez is supported by the Swiss National Science Foundation (185897) and the National Center of Competence in Research (NCCR) SYNAPSY - The Synaptic Bases of Mental Diseases, funded as well by the Swiss National Science Foundation (51AU40-1257).S

Innovative Approaches for Organizing an Inclusive Optics and Photonics Conference in Virtual Format

The COVID pandemic is forcing the renewal of scientific conferences, offering opportunities to introduce technological and inclusive developments. Our analysis focuses on the implementation of inclusive practices for female and early-career researchers in a virtual scientific conference. This organization approach was applied in the XIII Spanish Optical Meeting (RNO2021), which was also characterized by avatars interacting in an online metaverse. The effectiveness of inclusive policies and novel technological tools was evaluated using the participation data and a post-conference survey. Our study reveals the high impact of inclusive actions and a strong interest in the scientific community to explore conference advances

Histone H1 regulates non-coding RNA turnover on chromatin in a m6A-dependent manner

Linker histones are highly abundant chromatin-associated proteins with well-established structural roles in chromatin and as general transcriptional repressors. In addition, it has been long proposed that histone H1 exerts context-specific effects on gene expression. Here, we identify a function of histone H1 in chromatin structure and transcription using a range of genomic approaches. In the absence of histone H1, there is an increase in the transcription of non-coding RNAs, together with reduced levels of m6A modification leading to their accumulation on chromatin and causing replication-transcription conflicts. This strongly suggests that histone H1 prevents non-coding RNA transcription and regulates non-coding transcript turnover on chromatin. Accordingly, altering the m6A RNA methylation pathway rescues the replicative phenotype of H1 loss. This work unveils unexpected regulatory roles of histone H1 on non-coding RNA turnover and m6A deposition, highlighting the intimate relationship between chromatin conformation, RNA metabolism, and DNA replication to maintain genome performance.Work at the M.G. lab was supported by the Spanish Ministry of Sciences and Innovation (BFU2016-78849-P and PID2019-105949GB-I00, co-financed by the European Union FEDER funds), a CSIC grant (2019AEP004), and a Salvador de Madariaga mobility grant (PRX19/00293). J.M.F.-J., C.S.-M., and J.I.-A. were supported by the Spanish Ministry of Sciences and Innovation fellowships (BES-2014-070050, BES-2017-079897, and PRE2020-095071, respectively); S.M.-V. was supported by a predoctoral fellowship from the Spanish Ministry of Education and Universities (FPU18/04794); and M.S.-P. was supported by an AGAUR-FI predoctoral fellowship co-financed by Generalitat de Catalunya and the European Social Fund. A.J. was supported by the Spanish Ministry of Sciences and Innovation (BFU2017-82805-C2-1-P and PID2020-112783GB-C21) and J.F.C. by core funding to the MRC Human Genetics Unit from the Medical Research Council (UK)

Lung cancer survival in never-smokers and exposure to residential radon: results of the LCRINS study

We aimed to evaluate lung cancer survival in never-smokers, both overall and specifically by sex, exposure to residential-radon, age, histological type, and diagnostic stage. We included lung cancer cases diagnosed in a multicentre, hospital-based, case-control-study of never-smoker patients, diagnosed from January-2011 to March-2015 (Lung Cancer Research In Never Smokers study). 369 never-smokers (79% women; median age 71 years; 80% adenocarcinoma; 66% stage IV) were included. Median overall survival, and at one, 3 and 5 years of diagnosis was 18.3 months, 61%, 32% and 22%, respectively. Higher median survival rates were obtained for: younger age, adenocarcinoma, actionable mutations, and earlier-stage at diagnosis. Higher indoor radon showed a higher risk of death in multivariate analysis. Median lung cancer survival in never-smokers seems higher than that in ever-smokers. Patients with actionable mutations have a significantly higher survival. Higher indoor-radon exposure has a negative effect on survivalThis paper was funded by the following competitive research grants awarded to the individual case-control studies, which are part of this pooled study: Galician Regional Authority (Xunta de Galicia): 10CSA208057PR “Risk factors of lung cancer in never smokers: a multicentre case-control study in the Northwest of Spain.” 2010. Spain; Carlos III Institute of Health (Instituto de Salud Carlos III), Ministry of Science and Innovation of Spain, grant number PI03/1248. 2003. Spain; Carlos III Institute of Health (grant FIS 92/0176) and the Galician Regional Health Authority (grant XUGA 91010). 1992. Spain; Galician Regional Authority: grant number XUGA 208001B93. 1993; Carlos III Institute of Health, Ministry of Science and Innovation of Spain, grant number PI13/01765. 2013. Spain; ISCIII - PI15/01211 - Cofinanciado FEDER. Spain.This paper was funded by the following competitive research grants awarded to the individual case-control studies, which are part of this pooled study: • Galician Regional Authority (Xunta de Galicia): 10CSA208057PR “Risk factors of lung cancer in never smokers: a multicentre case-control study in the Northwest of Spain.” 2010. Spain. • Carlos III Institute of Health (Instituto de Salud Carlos III), Ministry of Science and Innovation of Spain, grant number PI03/1248. 2003. Spain. • Carlos III Institute of Health (grant FIS 92/0176) and the Galician Regional Health Authority (grant XUGA 91010). 1992. Spain. • Galician Regional Authority: grant number XUGA 208001B93. 1993. • Carlos III Institute of Health, Ministry of Science and Innovation of Spain, grant number PI13/01765. 2013. Spain. • ISCIII - PI15/01211 - Cofinanciado FEDER. Spain

Rationale, design and preliminary results of the GALIPEMIAS study (prevalence and lipid control of familial dyslipidemia in Galicia, northwest Spain)

[Abstract] Aims. There is little information on the familial nature of dyslipidemias in the Spanish population. This knowledge could have potential diagnostic and treatment implications. The objective of the GALIPEMIAS study was to determine the prevalence of familial dyslipidemia in Galicia, as well as determine the degree of lipid control in the participants. Prevalence of atherosclerotic cardiovascular disease (ASCVD) was also estimated. This paper presents the design, methodology and selected preliminary results. Methodology. A cross‐sectional study was performed in the population aged ≥18 years using cluster sampling and then random sampling. A sample of 1000 subjects was calculated and divided into three sequential phases with a specific methodology for each one. Phase I: selection of subjects from the general population and collection of informed consent documents; Phase II: collection of data from the digital clinical history to select subjects with dyslipidemia according to study criteria; Phase III: personal interview, blood analysis, family tree, and definitive diagnosis of dyslipidemia. Prevalence of different diseases and active medication was analysed. Corrected prevalence (to the reference population) of different risk factors and ASCVD was estimated. Results. Phase I participation was 89.5%. We extracted complete information from 93% of the participants (Phase II). According to the study′s own criteria, 56.5% (n = 527) of the participants had some form of dyslipidemia and almost 33.7% of them had familial dyslipidemia with autosomal dominant inherit pattern. The corrected prevalence of ASCVD was 5.1% (95% CI 3.1‐7.2). Conclusions. Dyslipidemia was the most prevalent cardiovascular risk factor in our population with an autosomal dominant inheritance pattern in one out of every three dyslipidemia cases. Approximately, 5.1% of the sample population aged ≥18 has suffered an episode of ACVD