DOT: a flexible multi-objective optimization framework for transferring features across single-cell and spatial omics.

Single-cell transcriptomics and spatially-resolved imaging/sequencing technologies have revolutionized biomedical research. However, they suffer from lack of spatial information and a trade-off of resolution and gene coverage, respectively. We propose DOT, a multi-objective optimization framework for transferring cellular features across these data modalities, thus integrating their complementary information. DOT uses genes beyond those common to the data modalities, exploits the local spatial context, transfers spatial features beyond cell-type information, and infers absolute/relative abundance of cell populations at tissue locations. Thus, DOT bridges single-cell transcriptomics data with both high- and low-resolution spatially-resolved data. Moreover, DOT combines practical aspects related to cell composition, heterogeneity, technical effects, and integration of prior knowledge. Our fast implementation based on the Frank-Wolfe algorithm achieves state-of-the-art or improved performance in localizing cell features in high- and low-resolution spatial data and estimating the expression of unmeasured genes in low-coverage spatial data.

Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function.

We designed and synthesized synI, which is ∼21.6% shorter than native chrI, the smallest chromosome in Saccharomyces cerevisiae. SynI was designed for attachment to another synthetic chromosome due to concerns surrounding potential instability and karyotype imbalance and is now attached to synIII, yielding the first synthetic yeast fusion chromosome. Additional fusion chromosomes were constructed to study nuclear function. ChrIII-I and chrIX-III-I fusion chromosomes have twisted structures, which depend on silencing protein Sir3. As a smaller chromosome, chrI also faces special challenges in assuring meiotic crossovers required for efficient homolog disjunction. Centromere deletions into fusion chromosomes revealed opposing effects of core centromeres and pericentromeres in modulating deposition of the crossover-promoting protein Red1. These effects extend over 100 kb and promote disproportionate Red1 enrichment, and thus crossover potential, on small chromosomes like chrI. These findings reveal the power of synthetic genomics to uncover new biology and deconvolute complex biological systems.

Rapid and sustainable HPLC method for the determination of uremic toxins in human plasma samples.

Protein-bound uremic toxins, mainly indoxyl sulfate (3-INDS), p-cresol sulfate (pCS), and indole-3-acetic acid (3-IAA) but also phenol (Pol) and p-cresol (pC), are progressively accumulated during chronic kidney disease (CKD). Their accurate measurement in biomatrices is demanded for timely diagnosis and adoption of appropriate therapeutic measures. Multianalyte methods allowing the establishment of a uremic metabolite profile are still missing. Hence, the aim of this work was to develop a rapid and sensitive method based on high-performance liquid chromatography with fluorescence detection for the simultaneous quantification of Pol, 3-IAA, pC, 3-INDS, and pCS in human plasma. Separation was attained in 12 min, using a monolithic C18 column and isocratic elution with acetonitrile and phosphate buffer containing an ion-pairing reagent, at a flow rate of 2 mL min-1. Standards were prepared in plasma and quantification was performed using the background subtraction approach. LOQ values were ≤ 0.2 µg mL-1 for all analytes except for pCS (LOQ of 2 µg mL-1). The method proved to be accurate (93.5-112%) and precise (CV ≤ 14.3%). The multianalyte application of the method, associated to a reduced sample volume (50 µL), a less toxic internal standard (eugenol) in comparison to the previously applied 2,6-dimethylphenol and 4-ethylphenol, and a green extraction solvent (ethanol), resulted in the AGREE score of 0.62 which is in line with the recent trend of green and sustainable analytical chemistry. The validated method was successfully applied to the analysis of plasma samples from control subjects exhibiting normal levels of uremic toxins and CKD patients presenting significantly higher levels of 3-IAA, pC, 3-INDS, and pCS that can be further investigated as biomarkers of disease progression.

Improvement in Solubility-Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-ß-cyclodextrin.

Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-ß-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-ß-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-ß-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-ß-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-ß-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.

Two pathways drive meiotic chromosome axis assembly in Saccharomyces cerevisiae.

Successful meiotic recombination, and thus fertility, depends on conserved axis proteins that organize chromosomes into arrays of anchored chromatin loops and provide a protected environment for DNA exchange. Here, we show that the stereotypic chromosomal distribution of axis proteins in Saccharomyces cerevisiae is the additive result of two independent pathways: a cohesin-dependent pathway, which was previously identified and mediates focal enrichment of axis proteins at gene ends, and a parallel cohesin-independent pathway that recruits axis proteins to broad genomic islands with high gene density. These islands exhibit elevated markers of crossover recombination as well as increased nucleosome density, which we show is a direct consequence of the underlying DNA sequence. A predicted PHD domain in the center of the axis factor Hop1 specifically mediates cohesin-independent axis recruitment. Intriguingly, other chromosome organizers, including cohesin, condensin, and topoisomerases, are differentially depleted from the same regions even in non-meiotic cells, indicating that these DNA sequence-defined chromatin islands exert a general influence on the patterning of chromosome structure.

Consequences and implications of the coronavirus disease (COVID-19) on pregnancy and newborns: A comprehensive systematic review and meta-analysis.

BACKGROUND: Pregnant patients are potentially vulnerable to COVID-19. OBJECTIVES: To clarify the clinical features of COVID-19 and analyze maternal/fetal morbidity and mortality and the obstetric and neonatal outcomes of pregnant patients. SEARCH STRATEGY: Embase, PubMed, Web of Science, CINAHAL, LILACS, Google Scholar, and Scopus. SELECTION CRITERIA: Articles published from December 2019 to February 2021. DATA COLLECTION AND ANALYSIS: The reviewers extracted relevant data from the full-text. Data synthesis was performed using the R-4.1.0 Project for Statistical Computing for Windows. The meta-analysis of the included studies was carried out using the random-effects model (DerSimonian and Laird). Heterogeneity was measured using I2 analysis. RESULTS: A total of 70 studies included 10 047 pregnant women with COVID-19, of whom 71.6% were in their third trimester. The most common symptoms were fever, cough, chest pain, dyspnea, and fatigue. Most newborns were delivered preterm (24%, 95% confidence interval [CI] 0.17-0.34, I2  = 93%) and via cesarean delivery (42%, 95% CI 0.38-0.47, I2  = 92%). There were 108 maternal mortalities (2%, 95% CI 0.01-0.03, I2  = 54%) and 50 abortions (5%, 95% CI 0.03-0.09, I2  = 73%). The neonatal outcomes included fetal distress (11%, 95% CI 0.06-0.19, I2  = 91%), birth weight (15%, 95% CI 0.10-0.21, I2  = 76%), APGAR <7 (19%, 95% CI 0.12-0.28, I2  = 43%), admission to the neonatal intensive care unit (28%, 95% CI 0.17-0.43, I2  = 90%), and fetal mortality (2%, 95% CI 0.01-0.03, I2  = 46%). CONCLUSION:  There was no evidence of severe acute respiratory syndrome coronavirus-2 in the placenta, breast milk, umbilical cord, and amniotic fluid of pregnant patients. PROSPERO registration number: CRD42020181519.

Long-term cancer survival prediction using multimodal deep learning.

The age of precision medicine demands powerful computational techniques to handle high-dimensional patient data. We present MultiSurv, a multimodal deep learning method for long-term pan-cancer survival prediction. MultiSurv uses dedicated submodels to establish feature representations of clinical, imaging, and different high-dimensional omics data modalities. A data fusion layer aggregates the multimodal representations, and a prediction submodel generates conditional survival probabilities for follow-up time intervals spanning several decades. MultiSurv is the first non-linear and non-proportional survival prediction method that leverages multimodal data. In addition, MultiSurv can handle missing data, including single values and complete data modalities. MultiSurv was applied to data from 33 different cancer types and yields accurate pan-cancer patient survival curves. A quantitative comparison with previous methods showed that Multisurv achieves the best results according to different time-dependent metrics. We also generated visualizations of the learned multimodal representation of MultiSurv, which revealed insights on cancer characteristics and heterogeneity.

Topoisomerases Modulate the Timing of Meiotic DNA Breakage and Chromosome Morphogenesis in Saccharomyces cerevisiae.

During meiotic prophase, concurrent transcription, recombination, and chromosome synapsis place substantial topological strain on chromosomal DNA, but the role of topoisomerases in this context remains poorly defined. Here, we analyzed the roles of topoisomerases I and II (Top1 and Top2) during meiotic prophase in Saccharomyces cerevisiae We show that both topoisomerases accumulate primarily in promoter-containing intergenic regions of actively transcribing genes, including many meiotic double-strand break (DSB) hotspots. Despite the comparable binding patterns, top1 and top2 mutations have different effects on meiotic recombination. TOP1 disruption delays DSB induction and shortens the window of DSB accumulation by an unknown mechanism. By contrast, temperature-sensitive top2-1 mutants exhibit a marked delay in meiotic chromosome remodeling and elevated DSB signals on synapsed chromosomes. The problems in chromosome remodeling were linked to altered Top2 binding patterns rather than a loss of Top2 catalytic activity, and stemmed from a defect in recruiting the chromosome remodeler Pch2/TRIP13 to synapsed chromosomes. No chromosomal defects were observed in the absence of TOP1 Our results imply independent roles for Top1 and Top2 in modulating meiotic chromosome structure and recombination.

EMIF Catalogue: A collaborative platform for sharing and reusing biomedical data.

OBJECTIVE: The collaboration and knowledge exchange between researchers are often hindered by the nonexistence of accurate information about which databases may support research studies. Even though a considerable amount of patient health information does exist, it is usually distributed and hidden in many institutions. The goal of this project is to provide, for any research community, a holistic view of biomedical datasets of interests, from which researchers can explore several distinct levels of granularity. METHODS: We developed a community-centered approach to facilitate data sharing while ensuring privacy. A dynamic schema allows exposing any metadata model about existing repositories. The framework was developed following a modular plugin-based architecture that facilitates the integration of internal and external tools. RESULTS: The EMIF Catalogue, a web platform for sharing and reusing biomedical data. Through this system, data custodians can publish and share different levels of information, while the researchers can search for databases that fulfill research requirements. CONCLUSIONS: The EMIF Catalogue currently fosters several distinct research communities, with different levels of data governance, combining, for instance, data available in pan-European EHR and Alzheimer cohorts. This portal is publicly available at https://emif-catalogue.eu.

Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on short chromosomes.

Faithful meiotic chromosome inheritance and fertility rely on the stimulation of meiotic crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs, likely in response to initiation of crossover repair. In Saccharomyces cerevisiae, this regulation requires the removal of the conserved DSB-promoting protein Hop1/HORMAD during chromosome synapsis. Here, we identify privileged end-adjacent regions (EARs) spanning roughly 100 kb near all telomeres that escape DSB down-regulation. These regions retain Hop1 and continue to break in pachynema despite normal synaptonemal complex deposition. Differential retention of Hop1 requires the disassemblase Pch2/TRIP13, which preferentially removes Hop1 from telomere-distant sequences, and is modulated by the histone deacetylase Sir2 and the nucleoporin Nup2. Importantly, the uniform size of EARs among chromosomes contributes to disproportionately high DSB and repair signals on short chromosomes in pachynema, suggesting that EARs partially underlie the curiously high recombination rate of short chromosomes.

SNP-ChIP: a versatile and tag-free method to quantify changes in protein binding across the genome.

BACKGROUND: Chromatin-immunoprecipitation followed by sequencing (ChIP-seq) is the method of choice for mapping genome-wide binding of chromatin-associated factors. However, broadly applicable methods for between-sample comparisons are lacking. RESULTS: Here, we introduce SNP-ChIP, a method that leverages small-scale intra-species polymorphisms, mainly SNPs, for quantitative spike-in normalization of ChIP-seq results. Sourcing spike-in material from the same species ensures antibody cross-reactivity and physiological coherence, thereby eliminating two central limitations of traditional spike-in approaches. We show that SNP-ChIP is robust to changes in sequencing depth and spike-in proportions, and reliably identifies changes in overall protein levels, irrespective of changes in binding distribution. Application of SNP-ChIP to test cases from budding yeast meiosis allowed discovery of novel regulators of the chromosomal protein Red1 and quantitative analysis of the DNA-damage associated histone modification γ-H2AX. CONCLUSION: SNP-ChIP is fully compatible with the intra-species diversity of humans and most model organisms and thus offers a general method for normalizing ChIP-seq results.

20 años de logros y nuevos retos en el Programa Cirugía Extramuros del Instituto Jalisciense de Cirugía Reconstructiva Dr. José Guerrerosantos / 20 years of achievements and new challenges in the Extramural Surgery Program Jalisco. Institute of Reconstructive Surgery Dr. José Guerrerosantos

Entre las múltiples estrategias del Instituto Jalisciense de Cirugía Reconstructiva Dr. José Guerrerosantos de Guadalajara (Jalisco, México) está la cobertura de servicios de salud y el brindar atención quirúrgica altruista y especializada a la población marginada del estado de Jalisco. Recogemos en el presente trabajo los resultados de más de 20 años de esfuerzo en conjunto con el Programa de Cirugía Extramuros, que se traducen en más de 10.000 pacientes consultados y más de 6.000 cirugías realizadas en más de 100 jornadas quirúrgicas fuera del Instituto, sin importar las condiciones sociales de pobreza y las condiciones geográficas de aislamiento de las zonas donde se trabajó. A través de este tiempo vemos como los resultados logrados implican ahora evolucionar hacia nuevas estrategias en la atención y control de calidad de los servicios quirúrgicos prestados, como gran reto a futuro para lograr soluciones quirúrgicas modernas con calidad humana y profesional

Among the many strategies of the Jalisco Institute of Reconstructive Surgery Dr. Jose Guerrerosantos in Guadalajara (Jalisco, México) is the coverage of health services and provide selfless and specialized surgical care to the underserved population of the state of Jalisco. The results of more than 20 years of effort with Extramural Surgery Program, results that translate to more than 10.000 patients visited and over 6.000 surgeries performed in more than 100 surgical workshops outside the Institute, without regardless of the social conditions of poverty and geographic isolation conditions. Through this time involving the results achieved now evolve new strategies in the care and quality control as a major challenge for the future to achieve modern surgical solutions to human and professional qualities

Intrinsic Immunity Shapes Viral Resistance of Stem Cells.

Stem cells are highly resistant to viral infection compared to their differentiated progeny; however, the mechanism is mysterious. Here, we analyzed gene expression in mammalian stem cells and cells at various stages of differentiation. We find that, conserved across species, stem cells express a subset of genes previously classified as interferon (IFN) stimulated genes (ISGs) but that expression is intrinsic, as stem cells are refractory to interferon. This intrinsic ISG expression varies in a cell-type-specific manner, and many ISGs decrease upon differentiation, at which time cells become IFN responsive, allowing induction of a broad spectrum of ISGs by IFN signaling. Importantly, we show that intrinsically expressed ISGs protect stem cells against viral infection. We demonstrate the in vivo importance of intrinsic ISG expression for protecting stem cells and their differentiation potential during viral infection. These findings have intriguing implications for understanding stem cell biology and the evolution of pathogen resistance.

A Dynamic Approach to Support Interoperability for Medical Reports Using DICOM SR.

The standardization of data structures for clinical observations in medical imaging environments is a relatively recent effort. DICOM standard defines a set of supplements for different medical reports denominated as Structured Reports (SR). In 2013, Integrating the Healthcare Enterprise (IHE) also followed this trend by publishing the profile Management of Radiology Report Templates (MRRT). However, the generalized adoption of these normalized reports has been delayed due to several factors. In fact, numerous medical institutions still use proprietary formats that do not promote sharing and remote access. New strategies to incentivise the adoption of normalized report templates are needed to make them interoperable between distinct applications. This article proposes a new method to automatically generate DICOM SR from distinct data sources. It encompasses a flexible mapping schema that can be used with distinct medical imaging modalities. Our ultimate goal is to encourage the usage of DICOM SR by providing an effortless method to convert proprietary formats into standard ones. Moreover, the developed methods can be also used for supporting IHE MRRT profiles, making the reports accessible across different information systems and institutions.

Upregulation of the Adhesin Gene EPA1 Mediated by PDR1 in Candida glabrata Leads to Enhanced Host Colonization.

Candida glabrata is the second most common Candida species causing disseminated infection, after C. albicans. C. glabrata is intrinsically less susceptible to the widely used azole antifungal drugs and quickly develops secondary resistance. Resistance typically relies on drug efflux with transporters regulated by the transcription factor Pdr1. Gain-of-function (GOF) mutations in PDR1 lead to a hyperactive state and thus efflux transporter upregulation. Our laboratory has characterized a collection of C. glabrata clinical isolates in which azole resistance was found to correlate with increased virulence in vivo. Contributing phenotypes were the evasion of adhesion and phagocytosis by macrophages and an increased adhesion to epithelial cells. These phenotypes were found to be dependent on PDR1 GOF mutation and/or C. glabrata strain background. In the search for the molecular effectors, we found that PDR1 hyperactivity leads to overexpression of specific cell wall adhesins of C. glabrata. Further study revealed that EPA1 regulation, in particular, explained the increase in adherence to epithelial cells. Deleting EPA1 eliminates the increase in adherence in an in vitro model of interaction with epithelial cells. In a murine model of urinary tract infection, PDR1 hyperactivity conferred increased ability to colonize the bladder and kidneys in an EPA1-dependent way. In conclusion, this study establishes a relationship between PDR1 and the regulation of cell wall adhesins, an important virulence attribute of C. glabrata. Furthermore, our data show that PDR1 hyperactivity mediates increased adherence to host epithelial tissues both in vitro and in vivo through upregulation of the adhesin gene EPA1. IMPORTANCE Candida glabrata is an important fungal pathogen in human diseases and is also rapidly acquiring drug resistance. Drug resistance can be mediated by the transcriptional activator PDR1, and this results in the upregulation of multidrug transporters. Intriguingly, this resistance mechanism is associated in C. glabrata with increased virulence in animal models and also with increased adherence to specific host cell types. The C. glabrata adhesin gene EPA1 is a major contributor of virulence and adherence to host cells. Here, we show that EPA1 expression is controlled by PDR1 independently of subtelomeric silencing, a known EPA1 regulation mechanism. Thus, a relationship exists between PDR1, EPA1 expression, and adherence to host cells, which is critical for efficient virulence. Our results demonstrate that acquisition of drug resistance is beneficial for C. glabrata in fungus-host relationships. These findings further highlight the challenges of the therapeutic management of C. glabrata infections in human patients.

Inhibiting fungal multidrug resistance by disrupting an activator-Mediator interaction.

Eukaryotic transcription activators stimulate the expression of specific sets of target genes through recruitment of co-activators such as the RNA polymerase II-interacting Mediator complex. Aberrant function of transcription activators has been implicated in several diseases. However, therapeutic targeting efforts have been hampered by a lack of detailed molecular knowledge of the mechanisms of gene activation by disease-associated transcription activators. We previously identified an activator-targeted three-helix bundle KIX domain in the human MED15 Mediator subunit that is structurally conserved in Gal11/Med15 Mediator subunits in fungi. The Gal11/Med15 KIX domain engages pleiotropic drug resistance transcription factor (Pdr1) orthologues, which are key regulators of the multidrug resistance pathway in Saccharomyces cerevisiae and in the clinically important human pathogen Candida glabrata. The prevalence of C. glabrata is rising, partly owing to its low intrinsic susceptibility to azoles, the most widely used antifungal agent. Drug-resistant clinical isolates of C. glabrata most commonly contain point mutations in Pdr1 that render it constitutively active, suggesting that this transcriptional activation pathway represents a linchpin in C. glabrata multidrug resistance. Here we perform sequential biochemical and in vivo high-throughput screens to identify small-molecule inhibitors of the interaction of the C. glabrata Pdr1 activation domain with the C. glabrata Gal11A KIX domain. The lead compound (iKIX1) inhibits Pdr1-dependent gene activation and re-sensitizes drug-resistant C. glabrata to azole antifungals in vitro and in animal models for disseminated and urinary tract C. glabrata infection. Determining the NMR structure of the C. glabrata Gal11A KIX domain provides a detailed understanding of the molecular mechanism of Pdr1 gene activation and multidrug resistance inhibition by iKIX1. We have demonstrated the feasibility of small-molecule targeting of a transcription factor-binding site in Mediator as a novel therapeutic strategy in fungal infectious disease.

A Routing Mechanism for Cloud Outsourcing of Medical Imaging Repositories.

Web-based technologies have been increasingly used in picture archive and communication systems (PACS), in services related to storage, distribution, and visualization of medical images. Nowadays, many healthcare institutions are outsourcing their repositories to the cloud. However, managing communications between multiple geo-distributed locations is still challenging due to the complexity of dealing with huge volumes of data and bandwidth requirements. Moreover, standard methodologies still do not take full advantage of outsourced archives, namely because their integration with other in-house solutions is troublesome. In order to improve the performance of distributed medical imaging networks, a smart routing mechanism was developed. This includes an innovative cache system based on splitting and dynamic management of digital imaging and communications in medicine objects. The proposed solution was successfully deployed in a regional PACS archive. The results obtained proved that it is better than conventional approaches, as it reduces remote access latency and also the required cache storage space.

Anatomy of an Extensible Open Source PACS.

The conception and deployment of cost effective Picture Archiving and Communication Systems (PACS) is a concern for small to medium medical imaging facilities, research environments, and developing countries' healthcare institutions. Financial constraints and the specificity of these scenarios contribute to a low adoption rate of PACS in those environments. Furthermore, with the advent of ubiquitous computing and new initiatives to improve healthcare information technologies and data sharing, such as IHE and XDS-i, a PACS must adapt quickly to changes. This paper describes Dicoogle, a software framework that enables developers and researchers to quickly prototype and deploy new functionality taking advantage of the embedded Digital Imaging and Communications in Medicine (DICOM) services. This full-fledged implementation of a PACS archive is very amenable to extension due to its plugin-based architecture and out-of-the-box functionality, which enables the exploration of large DICOM datasets and associated metadata. These characteristics make the proposed solution very interesting for prototyping, experimentation, and bridging functionality with deployed applications. Besides being an advanced mechanism for data discovery and retrieval based on DICOM object indexing, it enables the detection of inconsistencies in an institution's data and processes. Several use cases have benefited from this approach such as radiation dosage monitoring, Content-Based Image Retrieval (CBIR), and the use of the framework as support for classes targeting software engineering for clinical contexts.

Architecture to Summarize Patient-Level Data Across Borders and Countries.

Translational medicine is becoming fundamental in promoting information flow between basic research and clinical practice, and in improving patients' health. The need for efficient systems to process and share information from multiple sources--including distinct areas of medicine--is a pressing need in biomedical research. Nevertheless, healthcare information systems are fragmented over different databases, medical institutions, and geographical locations. There are already several approaches to tackle this problem based on centralized or distributed solutions. Nonetheless, mainly due to privacy reasons, these models only work for specific silos. In this paper, we present a new ecosystem for connecting database owners and researchers. Our approach consists of gathering, via a common fingerprint, an extensive characterization of dispersed databases. This fingerprint typically contains high-level aggregated information addressing questions at a population level and allowing, for instance, quick identification of databases with data that may help to answer a specific research question. This work is being conducted in the context of EMIF (European Medical Information Framework), an IMI (The Innovative Medicines Initiative) joint undertaking funded project, wherein the Catalogue is being used to collect data from cohorts and Electronic Health Record systems of several European countries.

Normalizing Heterogeneous Medical Imaging Data to Measure the Impact of Radiation Dose.

The production of medical imaging is a continuing trend in healthcare institutions. Quality assurance for planned radiation exposure situations (e.g. X-ray, computer tomography) requires examination-specific set-ups according to several parameters, such as patient's age and weight, body region and clinical indication. These data are normally stored in several formats and with different nomenclatures, which hinder the continuous and automatic monitoring of these indicators and the comparison between several institutions and equipment. This article proposes a framework that aggregates, normalizes and provides different views over collected indicators. The developed tool can be used to improve the quality of radiologic procedures and also for benchmarking and auditing purposes. Finally, a case study and several experimental results related to radiation exposure and productivity are presented and discussed.