Inferences on the evolution of the ascorbic acid synthesis pathway in insects using Phylogenetic Tree Collapser (PTC), a tool for the automated collapsing of phylogenetic trees using taxonomic information.

When inferring the evolution of a gene/gene family, it is advisable to use all available coding sequences (CDS) from as many species genomes as possible in order to infer and date all gene duplications and losses. Nowadays, this means using hundreds or even thousands of CDSs, which makes the inferred phylogenetic trees difficult to visualize and interpret. Therefore, it is useful to have an automated way of collapsing large phylogenetic trees according to a taxonomic term decided by the user (family, class, or order, for instance), in order to highlight the minimal set of sequences that should be used to recapitulate the full history of the gene/gene family being studied at that taxonomic level, that can be refined using additional software. Here we present the Phylogenetic Tree Collapser (PTC) program (https://github.com/pegi3s/phylogenetic-tree-collapser), a flexible tool for automated tree collapsing using taxonomic information, that can be easily used by researchers without a background in informatics, since it only requires the installation of Docker, Podman or Singularity. The utility of PTC is demonstrated by addressing the evolution of the ascorbic acid synthesis pathway in insects. A Docker image is available at Docker Hub (https://hub.docker.com/r/pegi3s/phylogenetic-tree-collapser) with PTC installed and ready-to-run.

Optical diagnosis in still images of colorectal polyps: comparison between expert endoscopists and PolyDeep, a Computer-Aided Diagnosis system.

Background: PolyDeep is a computer-aided detection and classification (CADe/x) system trained to detect and classify polyps. During colonoscopy, CADe/x systems help endoscopists to predict the histology of colonic lesions. Objective: To compare the diagnostic performance of PolyDeep and expert endoscopists for the optical diagnosis of colorectal polyps on still images. Methods: PolyDeep Image Classification (PIC) is an in vitro diagnostic test study. The PIC database contains NBI images of 491 colorectal polyps with histological diagnosis. We evaluated the diagnostic performance of PolyDeep and four expert endoscopists for neoplasia (adenoma, sessile serrated lesion, traditional serrated adenoma) and adenoma characterization and compared them with the McNemar test. Receiver operating characteristic curves were constructed to assess the overall discriminatory ability, comparing the area under the curve of endoscopists and PolyDeep with the chi- square homogeneity areas test. Results: The diagnostic performance of the endoscopists and PolyDeep in the characterization of neoplasia is similar in terms of sensitivity (PolyDeep: 89.05%; E1: 91.23%, p=0.5; E2: 96.11%, p<0.001; E3: 86.65%, p=0.3; E4: 91.26% p=0.3) and specificity (PolyDeep: 35.53%; E1: 33.80%, p=0.8; E2: 34.72%, p=1; E3: 39.24%, p=0.8; E4: 46.84%, p=0.2). The overall discriminative ability also showed no statistically significant differences (PolyDeep: 0.623; E1: 0.625, p=0.8; E2: 0.654, p=0.2; E3: 0.629, p=0.9; E4: 0.690, p=0.09). In the optical diagnosis of adenomatous polyps, we found that PolyDeep had a significantly higher sensitivity and a significantly lower specificity. The overall discriminative ability of adenomatous lesions by expert endoscopists is significantly higher than PolyDeep (PolyDeep: 0.582; E1: 0.685, p < 0.001; E2: 0.677, p < 0.0001; E3: 0.658, p < 0.01; E4: 0.694, p < 0.0001). Conclusion: PolyDeep and endoscopists have similar diagnostic performance in the optical diagnosis of neoplastic lesions. However, endoscopists have a better global discriminatory ability than PolyDeep in the optical diagnosis of adenomatous polyps.

Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron-BA.1 variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the United States became increasingly significant. The number of detected introductions varied from 96 and 101 for Alpha and Delta to 39 for Omicron-BA.1. Most of these introductions left a low number of descendants (<10), suggesting a limited impact on the evolution of the pandemic in Galicia. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of SARS-CoV-2 transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the USA became increasingly significant. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

PanDrugs2: prioritizing cancer therapies using integrated individual multi-omics data.

Genomics studies routinely confront researchers with long lists of tumor alterations detected in patients. Such lists are difficult to interpret since only a minority of the alterations are relevant biomarkers for diagnosis and for designing therapeutic strategies. PanDrugs is a methodology that facilitates the interpretation of tumor molecular alterations and guides the selection of personalized treatments. To do so, PanDrugs scores gene actionability and drug feasibility to provide a prioritized evidence-based list of drugs. Here, we introduce PanDrugs2, a major upgrade of PanDrugs that, in addition to somatic variant analysis, supports a new integrated multi-omics analysis which simultaneously combines somatic and germline variants, copy number variation and gene expression data. Moreover, PanDrugs2 now considers cancer genetic dependencies to extend tumor vulnerabilities providing therapeutic options for untargetable genes. Importantly, a novel intuitive report to support clinical decision-making is generated. PanDrugs database has been updated, integrating 23 primary sources that support >74K drug-gene associations obtained from 4642 genes and 14 659 unique compounds. The database has also been reimplemented to allow semi-automatic updates to facilitate maintenance and release of future versions. PanDrugs2 does not require login and is freely available at https://www.pandrugs.org/.

Negative Samples for Improving Object Detection-A Case Study in AI-Assisted Colonoscopy for Polyp Detection.

Deep learning object-detection models are being successfully applied to develop computer-aided diagnosis systems for aiding polyp detection during colonoscopies. Here, we evidence the need to include negative samples for both (i) reducing false positives during the polyp-finding phase, by including images with artifacts that may confuse the detection models (e.g., medical instruments, water jets, feces, blood, excessive proximity of the camera to the colon wall, blurred images, etc.) that are usually not included in model development datasets, and (ii) correctly estimating a more realistic performance of the models. By retraining our previously developed YOLOv3-based detection model with a dataset that includes 15% of additional not-polyp images with a variety of artifacts, we were able to generally improve its F1 performance in our internal test datasets (from an average F1 of 0.869 to 0.893), which now include such type of images, as well as in four public datasets that include not-polyp images (from an average F1 of 0.695 to 0.722).

Effect of TiO2 Nanoparticles and Extrusion Process on the Physicochemical Properties of Biodegradable and Active Cassava Starch Nanocomposites.

Biodegradable polymers have been strongly recognized as an alternative to replace traditional petrochemical plastics, which have become a global problem due to their long persistence in the environment. In this work, the effect of the addition of titanium dioxide nanoparticles (TiO2NP) on the morphology, physicochemical properties and biodegradation under industrial composting conditions of cassava starch-based nanocomposites obtained by extrusion at different screw speeds (80 and 120 rpm) were investigated. Films performed at 120 rpm (S120 and S120-TiO2NP) showed completely processed starch and homogeneously distributed nanoparticles, leading to much more flexible nanocomposites than those obtained at 80 rpm. The incorporation of TiO2NP led to an increase in storage modulus of all films and, in the case of S120-TiO2NP, to higher strain at break values. From the Kohlrausch-Williams-Watts theoretical model (KWW), an increase in the relaxation time of the nanocomposites was observed due to a decrease in the number of polymer chains involved in the relaxation process. Additionally, S120-TiO2NP showed effective protection against UV light, greater hydrophobicity and faster biodegradation in compost, resulting in a promising material for food packaging applications.

Performance of Convolutional Neural Networks for Polyp Localization on Public Colonoscopy Image Datasets.

Colorectal cancer is one of the most frequent malignancies. Colonoscopy is the de facto standard for precancerous lesion detection in the colon, i.e., polyps, during screening studies or after facultative recommendation. In recent years, artificial intelligence, and especially deep learning techniques such as convolutional neural networks, have been applied to polyp detection and localization in order to develop real-time CADe systems. However, the performance of machine learning models is very sensitive to changes in the nature of the testing instances, especially when trying to reproduce results for totally different datasets to those used for model development, i.e., inter-dataset testing. Here, we report the results of testing of our previously published polyp detection model using ten public colonoscopy image datasets and analyze them in the context of the results of other 20 state-of-the-art publications using the same datasets. The F1-score of our recently published model was 0.88 when evaluated on a private test partition, i.e., intra-dataset testing, but it decayed, on average, by 13.65% when tested on ten public datasets. In the published research, the average intra-dataset F1-score is 0.91, and we observed that it also decays in the inter-dataset setting to an average F1-score of 0.83.

Evaluation of neurotrophic factors and education level as predictors of cognitive decline in alcohol use disorder.

Cognitive reserve (CR) is the capability of an individual to cope with a brain pathology through compensatory mechanisms developed through cognitive stimulation by mental and physical activity. Recently, it has been suggested that CR has a protective role against the initiation of substance use, substance consumption patterns and cognitive decline and can improve responses to treatment. However, CR has never been linked to cognitive function and neurotrophic factors in the context of alcohol consumption. The present cross-sectional study aims to evaluate the association between CR (evaluated by educational level), cognitive impairment (assessed using a frontal and memory loss assessment battery) and circulating levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in patients with alcohol use disorder (AUD). Our results indicated that lower educational levels were accompanied by earlier onset of alcohol consumption and earlier development of alcohol dependence, as well as impaired frontal cognitive function. They also suggest that CR, NT-3 and BDNF may act as compensatory mechanisms for cognitive decline in the early stages of AUD, but not in later phases. These parameters allow the identification of patients with AUD who are at risk of cognitive deterioration and the implementation of personalized interventions to preserve cognitive function.

Compi: a framework for portable and reproducible pipelines.

Compi is an application framework to develop end-user, pipeline-based applications with a primary emphasis on: (i) user interface generation, by automatically generating a command-line interface based on the pipeline specific parameter definitions; (ii) application packaging, with compi-dk, which is a version-control-friendly tool to package the pipeline application and its dependencies into a Docker image; and (iii) application distribution provided through a public repository of Compi pipelines, named Compi Hub, which allows users to discover, browse and reuse them easily. By addressing these three aspects, Compi goes beyond traditional workflow engines, having been specially designed for researchers who want to take advantage of common workflow engine features (such as automatic job scheduling or logging, among others) while keeping the simplicity and readability of shell scripts without the need to learn a new programming language. Here we discuss the design of various pipelines developed with Compi to describe its main functionalities, as well as to highlight the similarities and differences with similar tools that are available. An open-source distribution under the Apache 2.0 License is available from GitHub (available at https://github.com/sing-group/compi). Documentation and installers are available from https://www.sing-group.org/compi. A specific repository for Compi pipelines is available from Compi Hub (available at https://www.sing-group.org/compihub.

DREIMT: a drug repositioning database and prioritization tool for immunomodulation.

MOTIVATION: Drug immunomodulation modifies the response of the immune system and can be therapeutically exploited in pathologies such as cancer and autoimmune diseases. RESULTS: DREIMT is a new hypothesis-generation web tool, which performs drug prioritization analysis for immunomodulation. DREIMT provides significant immunomodulatory drugs targeting up to 70 immune cells subtypes through a curated database that integrates 4960 drug profiles and ∼2600 immune gene expression signatures. The tool also suggests potential immunomodulatory drugs targeting user-supplied gene expression signatures. Final output includes drug-signature association scores, FDRs and downloadable plots and results tables. AVAILABILITYAND IMPLEMENTATION: http://www.dreimt.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Potential association of plasma lysophosphatidic acid (LPA) species with cognitive impairment in abstinent alcohol use disorders outpatients.

Lysophosphatidic acid (LPA) species are bioactive lipids participating in neurodevelopmental processes. The aim was to investigate whether the relevant species of LPA were associated with clinical features of alcohol addiction. A total of 55 abstinent alcohol use disorder (AUD) patients were compared with 34 age/sex/body mass index-matched controls. Concentrations of total LPA and 16:0-LPA, 18:0-LPA, 18:1-LPA, 18:2-LPA and 20:4-LPA species were quantified and correlated with neuroplasticity-associated growth factors including brain derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and IGF-2, and neurotrophin-3 (NT-3). AUD patients showed dysexecutive syndrome (22.4%) and memory impairment (32.6%). Total LPA, 16:0-LPA, 18:0-LPA and 18:1-LPA concentrations, were decreased in the AUD group compared to control group. Total LPA, 16:0-LPA, 18:2-LPA and 20:4-LPA concentrations were decreased in men compared to women. Frontal lobe functions correlated with plasma LPA species. Alcohol-cognitive impairments could be related with the deregulation of the LPA species, especially in 16:0-LPA, 18:1-LPA and 20:4-LPA. Concentrations of BDNF correlated with total LPA, 18:2-LPA and 20:4-LPA species. The relation between LPA species and BDNF is interesting in plasticity and neurogenesis functions, their involvement in AUD might serve as a biomarker of cognitive impairment.

An RNA-seq Based Machine Learning Approach Identifies Latent Tuberculosis Patients With an Active Tuberculosis Profile.

A better understanding of the response against Tuberculosis (TB) infection is required to accurately identify the individuals with an active or a latent TB infection (LTBI) and also those LTBI patients at higher risk of developing active TB. In this work, we have used the information obtained from studying the gene expression profile of active TB patients and their infected -LTBI- or uninfected -NoTBI- contacts, recruited in Spain and Mozambique, to build a class-prediction model that identifies individuals with a TB infection profile. Following this approach, we have identified several genes and metabolic pathways that provide important information of the immune mechanisms triggered against TB infection. As a novelty of our work, a combination of this class-prediction model and the direct measurement of different immunological parameters, was used to identify a subset of LTBI contacts (called TB-like) whose transcriptional and immunological profiles are suggestive of infection with a higher probability of developing active TB. Validation of this novel approach to identifying LTBI individuals with the highest risk of active TB disease merits further longitudinal studies on larger cohorts in TB endemic areas.

Metatax: Metataxonomics with a Compi-Based Pipeline for Precision Medicine.

The human body immune system, metabolism and homeostasis are affected by microbes. Dysbiosis occurs when the homeostatic equilibrium is disrupted due to an alteration in the normal microbiota of the intestine. Dysbiosis can cause cancer, and also affect a patient's ability to respond to treatment. Metataxonomics seeks to identify the bacteria present in a biological sample, based on the sequencing of the 16S rRNA genetic marker. Precision medicine attempts to find relationships between the microbiota and the risk of acquiring cancer, and design new therapies targeting bacteria. Flexible and portable bioinformatic pipelines are necessary to be able to bring metataxonomics to the clinical field, which allow groups of biological samples to be classified according to their diversity in the microbiota. With this aim we implemented Metatax, a new pipeline to analyze biological samples based on 16S rRNA gene sequencing. The results obtained with our pipeline should complement those obtained by sequencing a patient's DNA and RNA, in addition to clinical data, to improve knowledge of the possible reasons for a disease or a worse response to treatment.

Cuerpo, Fenomenología y Desarrollo / Body, Phenomenology and developmental

En el contexto de la psicología del desarrollo, el tema del cuerpo ha ocupado un lugar central en las discusiones. En algunas posiciones este concepto ocupa un lugar secundario, mientras que en otros asume un papel protagónico en la explicación de la cognición. Luego de realizar un examen crítico de las suposiciones que en las teorías del desarrollo psicológico vinculan el cuerpo y la cognición, se aboga por una vía desde la cual es posible repensar las discusiones contemporáneas acerca del desarrollo psicológico y la naturaleza de la experiencia consciente. Se propone una visión del desarrollo cognitivo enraizada en la fenomenología y que retoma discusiones contemporáneas de la psicología cognitiva y la filosofía de la mente.

Specifically, in the context of developmental psychology, the body occupies a central place in explanations of cognitive structuring. In Piaget's theory, sensorimotor accomplishments in childhood constitute the cornerstone of more complex forms of cognition such as representation or abstract thinking. After a critical examination of some of the assumptions that link body and cognition, which lead to a misunderstanding of this relationship, we advocate for a phenomenological approach of the body that lets us rethink the connection with cognition, including central aspects of contemporary discussions concerning the nature of conscious experience.

Gold Standard Evaluation of an Automatic HAIs Surveillance System.

Hospital-acquired Infections (HAIs) surveillance, defined as the systematic collection of data related to a certain health event, is considered an essential dimension for a prevention HAI program to be effective. In recent years, new automated HAI surveillance methods have emerged with the wide adoption of electronic health records (EHR). Here we present the validation results against the gold standard of HAIs diagnosis of the InNoCBR system deployed in the Ourense University Hospital Complex (Spain). Acting as a totally autonomous system, InNoCBR achieves a HAI sensitivity of 70.83% and a specificity of 97.76%, with a positive predictive value of 77.24%. The kappa index for infection type classification is 0.67. Sensitivity varies depending on infection type, where bloodstream infection attains the best value (93.33%), whereas the respiratory infection could be improved the most (53.33%). Working as a semi-automatic system, InNoCBR reaches a high level of sensitivity (81.73%), specificity (99.47%), and a meritorious positive predictive value (94.33%).

Evaluation of malpractice litigation in thyroid disease in the National Health Service.

Objectives: Thyroid disease is managed by primary and a range of secondary care specialties. Interventions for common thyroid conditions are effective, but delays in diagnosis, ineffective or inappropriate treatment may affect outcomes and be subject to litigation. This study aimed to analyze trends in thyroid malpractice litigation in the UK over a 14-year period.Methods: This retrospective cohort study analyzed negligence claims recorded by the NHS Litigation Authority from 2002 to 2016. Data on incident details, outcomes, time to settlement, costs, and specialties involved were collected and analyzed.Results: Out of 189 cases reviewed, an outcome was decided in 134 cases; of which, 67.9% were successful for the claimant, resulting in compensation being paid. The most common reasons for successful claims were treatment complications (47 cases) and delay or failure of diagnosis (22 cases). Nerve and/or vocal cord damage and hypoparathyroidism were cited in 12 and 3 cases, respectively. Common specialties involved in successful claims were general surgery, ENT and endocrinology. The median (range) costs paid for compensation were £50,701.35 (£189.00 to £4.5 million). The median (interquartile range) time from incident to settlement was 1254 (992-1756) days. The number of claims (overall and successful) has reduced over the 14-year period, but there has been no change in the total cost per successful claim from 2002 to 2014 (p = 0.151).Conclusion: This overview demonstrates common causes and identifies trends in thyroid malpractice litigation in the UK, highlighting the significant costs incurred. The outcomes of the study will provide a basis to enable clinicians to avoid potential pitfalls and formulate guidelines to minimize risk.

Oleoylethanolamide Modulates BDNF-ERK Signaling and Neurogenesis in the Hippocampi of Rats Exposed to Δ9-THC and Ethanol Binge Drinking During Adolescence.

Oleoylethanolamide is an endogenous NAE that modulates ethanol-seeking behavior and ethanol-induced neuroinflammation. In the present study we further analyze the role of OEA in hippocampal neurogenesis, BDNF-ERK signaling, and spatial memory that are affected by alcohol. Additionally, we addressed the effects of OEA on the association of alcohol and cannabis, a frequent combination in human alcohol addicts, and whose long-term effects are far from being understood. To this end, OEA (10 mg/kg/day, i.p.) was pharmacologically administered for 5 days/week in a preclinical model of adolescent rats with binge-like consumption (1 day/week) of ethanol (3 g/kg, i.g.) combined or not with acute administrations of Δ9-THC (5 mg/kg, i.p.) for 5 weeks. OEA restored ethanol/THC-related decreases in both short-term spatial memory (spontaneous alternation by Y-maze) and circulating levels of BDNF, reduced cell proliferation (Mki67 and IdU+ cells) and maturation (Dcx, Calb1), and improved cell survival (Casp3 and BrdU+ cells) in the dorsal hippocampus. Interestingly, OEA alone or combined with THC also decreased the mRNA levels of neurotrophic factors (Bdnf, Ntf3) and the NT3 receptor TrkC, but increased the BDNF receptor TrkB in the hippocampus of ethanol-exposed rats. These effects were likely associated with a OEA-specific phosphorylation of AKT and ERK1, key signaling regulators of cell proliferation and survival. These results suggest a regulatory role of OEA in short-term spatial memory and hippocampal neurogenesis through BDNF/AKT/ERK1 signaling in response to acute THC in an alcoholic context during adolescence.

Alcohol-induced cognitive deficits are associated with decreased circulating levels of the neurotrophin BDNF in humans and rats.

Chronic alcohol consumption is associated with neurocognitive and memory deficits, dramatically affecting plasticity and connectivity, with maximal expression as dementia. Neurotrophic factors may contribute to alcohol-related cognitive decline. For further investigation, a cross-sectional study was performed to evaluate the association of cognitive impairment, by using frontal assessment battery, and memory loss, using memory failures everyday, with the circulating levels of the neurotrophin brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) in abstinent subjects with alcohol use disorders (AUDs, N = 58, average of 17.9 years of problematic use and 4.3 months of abstinence) compared with healthy control subjects (N = 22). This association was also explored in a pre-clinical model of adolescent rats chronically exposed to alcohol up to adulthood (~77 days old) in a three-bottle free-choice (5-10-20 percent), repeated abstinence and relapse paradigm. AUD subjects had low educational level and cognitive impairment associated with teenage consumption and lower circulating levels of BDNF and NT-3. Only BDNF concentration showed a positive correlation with frontal assessment battery in AUD patients. In the ethanol-exposed rats, the plasma levels of BDNF and NT-3 were also decreased, and a negative correlation between hippocampal Bdnf mRNA levels and recognition memory was found. The ethanol-exposed rat hippocampus showed a decrease in the mRNA levels of neurotrophic (Bdnf and Ntf-3) and neurogenic (Mki67, Sox2, Dcx, Ncam1 and Calb1) factors, associated to a deactivation of the neurogenic regulator mitogen-activated protein kinase extracellular signal-regulated kinase. Results suggest a relevant role of BDNF/extracellular signal-regulated kinase 2 signaling in alcohol-induced cognitive impairment and suggest that early alcohol exposure-derived effects on cognition are associated with neurotrophin signaling deficits.