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It is undeniable that computing has settled in the modern world. Many elements have enabled global digitization and products are being developed faster, largely through the use of third-party services. However, the systems developed, whether a proprietary or third party, can have degradation or service outages. Having an automatic system for the generation of incidents would allow acting as soon as possible on specific problems in the services and the development of a system that allows this automation is the main objective of this work.

High Grade B Cell Lymphoma, NOS, and High Grade B Cell Lymphoma with Dual Hit or Triple Hit have been recently recategorized in the 2016 revision of the WHO classification of lymphoid neoplasms. In this study we have characterized the genetic, histopathological, and clinical features of a series of this type of lymphoid neoplasia (17 HGBCL NOS and 53 HGBCL DH/TH).HGBCL NOS showed better response to first line treatment than HGBCL with DH/TH but no significant differences in PFS or OS were found between the two categories. Survival analysis in the whole cohort of cases found that only the presence of BCL2 translocation was significantly associated with PFS. Other clinical features such as IPI, LDH or stage were equivalent in both categories. Furthermore, both high grade and DLBCL morphological patterns showed equivalent PFS and OS in this set of High grade BCL NOS/DH/TH.Key pointsBCL2 translocation in High Grade B Cell Lymphoma NOS and High Grade B Cell Lymphoma with DH/TH is associated with reduced progression free survival.Both high grade and DLBCL morphological patterns showed equivalent outcome regarding PFS and OS in HGBCL.

Au-Kline syndrome (AKS) is a neurodevelopmental disorder associated with multiple malformations and a characteristic facial gestalt. The first individuals ascertained carried de novo loss-of-function (LoF) variants in HNRNPK. Here, we report 32 individuals with AKS (26 previously unpublished), including 13 with de novo missense variants. We propose new clinical diagnostic criteria for AKS that differentiate it from the clinically overlapping Kabuki syndrome and describe a significant phenotypic expansion to include individuals with missense variants who present with subtle facial features and few or no malformations. Many gene-specific DNA methylation (DNAm) signatures have been identified for neurodevelopmental syndromes. Because HNRNPK has roles in chromatin and epigenetic regulation, we hypothesized that pathogenic variants in HNRNPK may be associated with a specific DNAm signature. Here, we report a unique DNAm signature for AKS due to LoF HNRNPK variants, distinct from controls and Kabuki syndrome. This DNAm signature is also identified in some individuals with de novo HNRNPK missense variants, confirming their pathogenicity and the phenotypic expansion of AKS to include more subtle phenotypes. Furthermore, we report that some individuals with missense variants have an "intermediate" DNAm signature that parallels their milder clinical presentation, suggesting the presence of an epi-genotype phenotype correlation. In summary, the AKS DNAm signature may help elucidate the underlying pathophysiology of AKS. This DNAm signature also effectively supported clinical syndrome delineation and is a valuable aid for variant interpretation in individuals where a clinical diagnosis of AKS is unclear, particularly for mild presentations. ispartof: AMERICAN JOURNAL OF HUMAN GENETICS vol:109 issue:10 pages:1867-1884 ispartof: location:United States status: published

The study of moral judgements often centres on moral dilemmas in which options consistent with deontological perspectives (that is, emphasizing rules, individual rights and duties) are in conflict with options consistent with utilitarian judgements (that is, following the greater good based on consequences). Greene et al. (2009) showed that psychological and situational factors (for example, the intent of the agent or the presence of physical contact between the agent and the victim) can play an important role in moral dilemma judgements (for example, the trolley problem). Our knowledge is limited concerning both the universality of these effects outside the United States and the impact of culture on the situational and psychological factors affecting moral judgements. Thus, we empirically tested the universality of the effects of intent and personal force on moral dilemma judgements by replicating the experiments of Greene et al. in 45 countries from all inhabited continents. We found that personal force and its interaction with intention exert influence on moral judgements in the US and Western cultural clusters, replicating and expanding the original findings. Moreover, the personal force effect was present in all cultural clusters, suggesting it is culturally universal. The evidence for the cultural universality of the interaction effect was inconclusive in the Eastern and Southern cultural clusters (depending on exclusion criteria). We found no strong association between collectivism/individualism and moral dilemma judgements. Including participants from 45 countries, Bago et al. find that the situational factors that affect moral reasoning are shared across countries, with diminished observed cultural variation., Comunidad de Madrid [2016-T1/SOC-1395, 2020-5A/SOC-19723]; AEI [PSI2017-85159-P]; UE/FEDER; National Science Centre, Poland [2017/01/X/HS6/01332, 2015/19/D/HS6/00641, 2019/35/B/HS6/00528]; Aarhus University Research Foundation (AUFF) [AUFF-E-2019-9-4]; ANR [ANR-17-EURE-0010]; ANR Labex IAST; Australian Research Council [DP180102384]; CAPES [88887.364180/2019-00]; Carlsberg Foundation [CF16-0444]; Independent Research Fund Denmark [7024-00057B]; Germany's Excellence Strategy [EXC 2126/1-390838866]; FONDECYT, CONICYT [11190980]; German Research Foundation [FOR-2150, LA 3566/1-2]; JSPS [18K03010]; JSPS KAKENHI [16H03079, 17H00875, 18K12015, 20H04581, 17H06342, 20K03479, 20KK0054, 20J21976]; Natural Science Foundation of China (NSFC) [31530032]; Key Technological Projects of Guangdong Province [2018B030335001]; National Science Foundation Graduate Research Fellowship [DGE-1839285]; Polish National Science Center; DFG Beethoven [2016/23/G/HS6/01775]; Portuguese National Foundation for Science and Technology [SFRH/BD/126304/2016, UID/PSI/03125/2019]; PRIN 2017 (Italian Ministry of Education and Research) [20178293XT]; PSA 006 BRA 008 Data Collection in Support of PSADM 001 Measurement Invariance Project; Foundation for Polish Science (START); National Science Centre [2020/36/T/HS6/00256, 2019/33/N/HS6/00054]; Slovak Research and Development Agency [APVV-18-0140, APVV-17-0418, PRIMUS/20/HUM/009, APVV-17-0596]; Social Sciences and Humanities Research Council of Canada [950-224884]; Swedish Research Council [2016-06793]; Project of Philosophy and Social Science Research in Colleges and Universities in Jiangsu Province [2020SJA0017], M.A. Vadillo was supported by 2016-T1/SOC-1395 and 2020-5A/SOC-19723 from Comunidad de Madrid, PSI2017-85159-P from AEI and UE/FEDER. M.P.-C. was supported by 2017/01/X/HS6/01332 from the National Science Centre, Poland. P.M. was supported by Aarhus University Research Foundation (AUFF), starting grant: AUFF-E-2019-9-4. B. Bago was supported by ANR grant ANR-17-EURE-0010 (Investissements d'Avenir programme) and ANR Labex IAST. R.M.R. was supported by the Australian Research Council (DP180102384). N.B.D. was supported by CAPES grant no. 88887.364180/2019-00. C.S., K.A.. and I. Zettler were supported by the Carlsberg Foundation (CF16-0444) and the Independent Research Fund Denmark (7024-00057B). J.L. was supported by EXC 2126/1-390838866 under Germany's Excellence Strategy. K.B. was supported by the following grants from the National Science Centre, Poland: (1) while working on the data collection, no. 2015/19/D/HS6/00641, (2) while working on the final version of the paper, no. 2019/35/B/HS6/00528. A.W. was supported by FONDECYT 11190980, CONICYT. A. Fleischmann was supported by the German Research Foundation (research unit grant FOR-2150, LA 3566/1-2). H.Y. was supported by JSPS grant 18K03010. Y.Y. was supported by JSPS KAKENHI (16H03079, 17H00875, 18K12015 and 20H04581). K.Q. was supported by JSPS KAKENHI (17H06342, 20K03479 and 20KK0054). A. Ikeda was supported by JSPS KAKENHI (20J21976). K.M.K. was supported by National Natural Science Foundation of China (NSFC) grant no. 31530032 and Key Technological Projects of Guangdong Province grant no. 2018B030335001. J.B.C. was supported by National Science Foundation Graduate Research Fellowship grant no. DGE-1839285. M. Parzuchowski, K. Rybus and N.M.S. were supported by Polish National Science Center and DFG Beethoven grant 2016/23/G/HS6/01775. A.C.S. was supported by Portuguese National Foundation for Science and Technology grant no. SFRH/BD/126304/2016. L. Boncinelli was supported by PRIN 2017 grant no. 20178293XT (Italian Ministry of Education and Research). M.F.F.R. was supported by PSA 006 BRA 008 Data Collection in Support of PSADM 001 Measurement Invariance Project. M. Misiak was supported by a scholarship from the Foundation for Polish Science (START) and by a scholarship from the National Science Centre (2020/36/T/HS6/00256). P.B. was supported by Slovak Research and Development Agency project no. APVV-18-0140. M.A. was supported by Slovak Research and Development Agency project no. APVV-17-0418 and project PRIMUS/20/HUM/009. A. Findor and M.H. were supported by the Slovak Research and Development Agency under contract no. APVV-17-0596. T.G. was supported by the Social Sciences and Humanities Research Council of Canada (no. 950-224884). P.P. was supported by the Swedish Research Council (2016-06793). Y.L. was supported by The Project of Philosophy and Social Science Research in Colleges and Universities in Jiangsu Province (grant no. 2020SJA0017). M. Kowal was supported by a scholarship from the National Science Centre (2019/33/N/HS6/00054). P.A. was supported by UID/PSI/03125/2019 from the Portuguese National Foundation for Science and Technology. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

In myelodysplastic syndromes (MDS), the 20q deletion [del(20q)] may cause deletion of the ASXL1 gene. We studied 153 patients with MDS and del(20q) to assess the incidence, prognostic value and impact on response to azacitidine (AZA) of ASXL1 chromosomal alterations and genetic mutations. Additionally, in vitro assay of the response to AZA in HAP1 (HAP1(WT)) and HAP1 ASXL1 knockout (HAP1(KN)) cells was performed. ASXL1 chromosomal alterations were detected in 44 patients (28 center dot 5%): 34 patients (22%) with a gene deletion (ASXL1(DEL)) and 10 patients (6 center dot 5%) with additional gene copies. ASXL1(DEL) was associated with a lower platelet count. The most frequently mutated genes were U2AF1 (16%), ASXL1 (14%), SF3B1 (11%), TP53 (7%) and SRSF2 (6%). ASXL1 alteration due to chromosomal deletion or genetic mutation (ASXL1(DEL)/ASXL1(MUT)) was linked by multivariable analysis with shorter overall survival [hazard ratio, (HR) 1 center dot 84; 95% confidence interval, (CI): 1 center dot 11-3 center dot 04; P = 0 center dot 018] and a higher rate for acute myeloid leukaemia progression (HR 2 center dot 47; 95% CI: 1 center dot 07-5 center dot 70, P = 0 center dot 034). ASXL1(DEL)/ASXL1(MUT) patients were correlated by univariable analysis with a worse response to AZA. HAP1(KN) cells showed more resistance to AZA compared to HAP1(WT) cells. In conclusion, ASXL1 alteration exerts a negative impact on MDS with del(20q) and could become useful for prognostic risk stratification and treatment decisions.

16 páginas, 7 figuras, 1 tabla. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (Perez-Riverolet al, 2019) partner repository with the dataset identifier PXD028959 and PXD028959. All data generated or analyzed during this study are included in the manuscript and supporting files., Dysfunction of RNA-binding proteins is often linked to a wide range of human disease, particularly with neurological conditions. Gemin5 is a member of the survival of the motor neurons (SMN) complex, a ribosome-binding protein and a translation reprogramming factor. Recently, pathogenic mutations in Gemin5 have been reported, but the functional consequences of these variants remain elusive. Here, we report functional and structural deficiencies associated with compound heterozygosity variants within the Gemin5 gene found in patients with neurodevelopmental disorders. These clinical variants are located in key domains of Gemin5, the tetratricopeptide repeat (TPR)-like dimerization module and the noncanonical RNA-binding site 1 (RBS1). We show that the TPR-like variants disrupt protein dimerization, whereas the RBS1 variant confers protein instability. All mutants are defective in the interaction with protein networks involved in translation and RNA-driven pathways. Importantly, the TPR-like variants fail to associate with native ribosomes, hampering its involvement in translation control and establishing a functional difference with the wild-type protein. Our study provides insights into the molecular basis of disease associated with malfunction of the Gemin5 protein., This work was supported by the Spanish Ministerio de Ciencia e Innovación (MICIN) and Fondo Europeo de Desarrollo Regional (AEI/FEDERUE) grants BFU2017-84492-R, PID2020-115096RB-I00 (to E Martinez-Salas), and RTI2018-098084-B-100 (to S Ramón-Maiques), Comunidad de Madrid (B2017/BMD-3770 to E Martinez-Salas), and an Institutional grant from Fundación Ramón Areces (to E Martinez-Salas).

The high incidence of Zika virus (ZIKV) infection in the period of 2015–2016 in Brazil may have affected linear height growth velocity (GV) in children exposed in utero to ZIKV. This study describes the growth velocity and nutritional status based on the World Organization (WHO) standards of children exposed to ZIKV during pregnancy and followed up in a tertiary unit, a reference for tropical and infectious diseases in the Amazon. Seventy-one children born between March 2016 and June 2018 were monitored for anthropometric indices: z-score for body mass index (BMI/A); weight (W/A); height (H/A) and head circumference (HC/A); and growth velocity. The mean age at the last assessment was 21.1 months (SD ± 8.93). Four children had congenital microcephaly and severe neurological impairment. The other 67 were non-microcephalic children (60 normocephalic and 7 macrocephalic); of these; 24.2% (16 children) had neurological alterations, and 28.8% (19 children) had altered neuropsychomotor development. Seventeen (24.2%) children had inadequate GV (low growth velocity). The frequencies of low growth among microcephalic and non-microcephalic patients are 25% (1 of 4 children) and 23.9% (16 of 67 children); respectively. Most children had normal BMI/A values during follow-up. Microcephalic patients showed low H/A and HC/A throughout the follow-up, with a significant reduction in the HC/A z-score. Non-microcephalic individuals are within the regular ranges for H/A; HC/A; and W/A, except for the H/A score for boys. This study showed low growth velocity in children with and without microcephaly, highlighting the need for continuous evaluation of all children born to mothers exposed to ZIKV during pregnancy.

SUMMARYBackgroundKBG syndrome is a highly variable neurodevelopmental disorder and clinical diagnostic criteria have changed as new patients have been published. Both loss-of-function sequence variants and large deletions (CNVs) involving ANKRD11 have been involved in KBG, but no genotype-phenotype correlation has been reported to date. This study presents the clinical and molecular characteristics of 67 new patients with KBG syndrome and the results of the first genotype-phenotype correlation leveraging data on 273 patients previously published.Methods67 patients with KBG syndrome were recruited through a Spanish collaborative effort and were assessed using a custom phenotypic questionnaire. The frequency of all features was calculated. Manifestations present in >50% of the patients and a “severity score” were used to perform a genotype-phenotype correlation in the 340 KBG patients.ResultsNeurodevelopmental delay (95%), comorbidites (82.8%), macrodontia (80.9%), triangular face (71%), characteristic ears (76%), nose (75.9%) and eyebrows (67.3%) were the most prevalent features in the 67 patients. The genotype-phenotype correlation yielded significant associations with the triangular face (71.1% in patients with sequence variants vs 45.2% in CNVs, p=0.015), short stature (62.5% variants in exon 9 vs. 27.8% outside; p=0.009) and macrodontia (with larger deletions, p=0.028), ID/ADHD/ASD (70.4% in c.1903_1907del vs. 89.4%; p=0.012) and a higher phenotypic score in patients with sequence variants compared with CNVs (p=0.005).ConclusionsWe present a detailed phenotypic description of KBG syndrome in the largest series of patients reported to date, provide evidence of a genotype-phenotype correlation between some KBG features and specific ANKRD11 aberrations, and propose updated clinical diagnostic criteria based on our findings.

[Abstract] Automatic prediction of the aesthetic value of images has received increasing attention in recent years. This is due, on the one hand, to the potential impact that predicting the aesthetic value has on practical applications. Even so, it remains a difficult task given the subjectivity and complexity of the problem. An image aesthetics assessment system was developed in recent years by our research group. In this work, its potential to be applied in commercial tasks is tested. With this objective, a set of three portals and three real estate agencies in Spain were taken as case studies. Images of their websites were taken to build the experimental dataset and a validation method was developed to test their original order with another proposed one according to their aesthetic value. So, in this new order, the images that have the high aesthetic score by the AI system will occupy the first positions of the portal. Relevant results were obtained, with an average increase of 52.54% in the number of clicks on the ads, in the experiment with Real Estate portals. A statistical analysis prove that there is a significant difference in the number of clicks after selecting the images with the AI system. This work is supported by the General Directorate of Culture, Education and University Management of Xunta de Galicia (Ref. ED431D 201716), Competitive Reference Groups (Ref. ED431C 201849) and Ministry of Science and Innovation project Society challenges (Ref. PID2020-118362RB-I00). We also wish to acknowledge the support received from the Centro de Investigación de Galicia “CITIC”, funded by Xunta de Galicia and the European Union (European Regional Development Fund- Galicia 2014-2020 Program), by grant ED431G 2019/01 Xunta de Galicia; ED431D 201716 Xunta de Galicia; ED431C 201849 Xunta de Galicia; ED431G 2019/01

The complete sequencing of the human genome has led to a major change in the way cancer diagnosis and treatment is understood, researched, and approached. In this context, the development of the omic sciences, bioinformatics, and molecular techniques has triggered a revolution in cancer research, having important consequences for the diagnosis, prognosis, and treatment of patients. This chapter provides an overview of the different bioinformatics technologies and applications currently applied in cancer research, focusing on their application to colorectal cancer and including from a molecular and genetic point of view to risk assessment and prevention.

Background: The use of corticosteroids may help control the cytokine storm occurring in acute respiratory failure due to the severe form of COVID-19. We evaluated the postacute effect of corticosteroids used during the acute phase, such as impairment in pulmonary function parameters, on day 120 (D120)-follow-up, in participants who survived over 28 days.Methods: This is a parallel, double-blind, randomized, placebo-controlled phase IIb clinical trial carried out between April 18 and October 9, 2020, conducted in hospitalized patients with clinical–radiological suspicion of COVID-19, aged 18 years or older, with SpO2 ≤ 94% on room air or requiring supplementary oxygen, or under invasive mechanical ventilation (IMV) in a referral center in Manaus, Western Brazilian Amazon. Intravenous methylprednisolone (MP) (0.5 mg/kg) was given two times daily for 5 days to these patients. The primary outcome used for this study was pulmonary function testing at day 120 follow-up visit.Results: Out of the total of surviving patients at day 28 (n = 246) from the Metcovid study, a total of 118 underwent satisfactory pulmonary function testing (62 in the placebo arm and 56 in the MP arm). The supportive treatment was similar between the placebo and MP groups (seven [11%] vs. four [7%]; P = 0.45). At hospital admission, IL-6 levels were higher in the MP group (P < 0.01). Also, the need for ICU (P = 0.06), need for IMV (P = 0.07), and creatine kinase (P = 0.05) on admission also tended to be higher in this group. In the univariate analysis, forced expiratory volume on 1st second of exhalation (FEV1) and forced vital capacity (FVC) at D120 follow-up were significantly higher in patients in the MP arm, being this last parameter also significantly higher in the multivariate analysis independently of IMV and IL-6 levels on admission.Conclusion: The use of steroids for at least 5 days in severe COVID-19 was associated with a higher FVC, which suggests that hospitalized COVID-19 patients might benefit from the use of MP in its use in the long-term, with less pulmonary restrictive functions, attributed to fibrosis.Trial Registration:ClinicalTrials.gov, Identifier: NCT04343729.

Gene set based phenotype enrichment analysis (detecting phenotypic terms that emerge as significant in a set of genes) can improve the rate of genetic diagnoses amongst other research purposes. To facilitate diverse phenotype analysis, we developed PhenoExam, a freely available R package for tool developers and a web interface for users, which performs: (1) phenotype and disease enrichment analysis on a gene set; (2) measures statistically significant phenotype similarities between gene sets and (3) detects significant differential phenotypes or disease terms across different databases. PhenoExam achieves these tasks by integrating databases or resources such as the HPO, MGD, CRISPRbrain, CTD, ClinGen, CGI, OrphaNET, UniProt, PsyGeNET, and Genomics England Panel App. PhenoExam accepts both human and mouse genes as input. We developed PhenoExam to assist a variety of users, including clinicians, computational biologists and geneticists. It can be used to support the validation of new gene-to-disease discoveries, and in the detection of differential phenotypes between two gene sets (a phenotype linked to one of the gene set but no to the other) that are useful for differential diagnosis and to improve genetic panels. We validated PhenoExam performance through simulations and its application to real cases. We demonstrate that PhenoExam is effective in distinguishing gene sets or Mendelian diseases with very similar phenotypes through projecting the disease-causing genes into their annotation-based phenotypic spaces. We also tested the tool with early onset Parkinson’s disease and dystonia genes, to show phenotype-level similarities but also potentially interesting differences. More specifically, we used PhenoExam to validate computationally predicted new genes potentially associated with epilepsy. Therefore, PhenoExam effectively discovers links between phenotypic terms across annotation databases through effective integration. The R package is available at https://github.com/alexcis95/PhenoExam and the Web tool is accessible at https://snca.atica.um.es/PhenoExamWeb/.

Correction to: Nature Human Behaviour https://doi.org/10.1038/s41562-022-01319-5, published online 14 April 2022.

Tatton-Brown-Rahman (TBRS) syndrome is a recently described overgrowth syndrome caused by loss of function variants in the DNMT3A gene. This gene encodes for a DNA methyltransferase 3 alpha, which is involved in epigenetic regulation, especially during embryonic development. Somatic variants in DNMT3A have been widely studied in different types of tumors, including acute myeloid leukemia, hematopoietic, and lymphoid cancers. Germline gain-of-function variants in this gene have been recently implicated in microcephalic dwarfism. Common clinical features of patients with TBRS include tall stature, macrocephaly, intellectual disability (ID), and a distinctive facial appearance. Differential diagnosis of TBRS comprises Sotos, Weaver, and Malan Syndromes. The majority of these disorders present other clinical features with a high clinical overlap, making necessary a molecular confirmation of the clinical diagnosis. We here describe seven new patients with variants in DNMT3A, four of them with neuropsychiatric disorders, including schizophrenia and psychotic behavior. In addition, one of the patients has developed a brain tumor in adulthood. This patient has also cerebral atrophy, aggressive behavior, ID, and abnormal facial features. Clinical evaluation of this group of patients should include a complete neuropsychiatric assessment together with psychological support in order to detect and manage abnormal behaviors such as aggressiveness, impulsivity, and attention deficit-hyperactivity disorder. TBRS should be suspected in patients with overgrowth, ID, tall stature, and macrocephaly, who also have some neuropsychiatric disorders without any genetic defects in the commonest overgrowth disorders. Molecular confirmation in these patients is mandatory., This project was supported by ISCII, FEDER funds grant: FIS-PI15/01481.

The signs of separation related problems (SRP) may vary according to the inner state that triggers them - for example we found earlier that dogs with owner-reported SRP were characterized with a predominance of whining during a short isolation from the owner, meanwhile barking occurred independently of the owner-reported SRP status. Based on the theory that the owner represents a resource for the dog we hypothesise that there is an association between the permissive and inconsistent behaviour of the owner and the reduced frustration threshold in the dog, which consequently will show specific signs of SRP. In our study, personality traits of the owner and the dog were measured with a questionnaire, while the separation behaviour was observed with an outdoor test. We found that dogs that rather barked than whined in the separation test had more likely a lenient owner. Dogs with owner-reported SRP whined less frequently than non-SRP dogs if they had lenient owners. The connection between the owner's permissiveness and the type of emitted vocalisation supports the theory that the owner's attitude towards the dog can be associated with the dogs' frustration-related SRP signs as they tend to respond with similar behaviours that occur in other frustrating situations.

[Abstract] The study of the intestinal microbiota is one of the biggest challenges in the current clinical environment. In this context, probiotics have been a focus of interest to achieve the stability of the intestinal microbiota, due to probiotics’ key role in its regulation. The development of an automated system that allows practitioners to easily search for the optimal probiotic is the main objective of this study. Although it is true that there have been previous attempts of applications with this purpose, only authorized probiotics available in the countries of origin, Canada and the USA, were included. This event was a limitation when looking for those endorsed in other countries such as Spain. Thus, a system has been developed from free and multiplatform technologies that allow its use without any cost, finding, in a simple way, those probiotics that would be ideal for each pathology, either from a browser or from a cell phone. This work was supported by the “Collaborative Project in Genomic Data Integration (CICLOGEN)” PI17/01826 funded by the Carlos III Health Institute from the Spanish National plan for Scientific and Technical Research and Innovation 2013–2016, the European Regional Development Funds (ERDF)—“A way to build Europe.”, the General Directorate of Culture, Education and University Management of Xunta de Galicia (Ref. ED431D 2017/16), the “Galician Network for Colorectal Cancer Research” (Ref. ED431D 2017/23) and Competitive Reference Groups (Ref. ED431C 2018/49). The funding body did not have a role in the experimental design, data collection, analysis and interpretation, and writing of this manuscript. CITIC, as a Research Center accredited by Galician University System, is funded by “Consellería de Cultura, Educación e Universidades” of Xunta de Galicia, 80% co-financed by the ERDF Funds, ERDF Operational Programme Galicia 2014-2020, and the remaining 20% by “Secretaría Xeral de Universidades” (Grant ED431G 2019/01) Xunta de Galicia; ED431D 2017/16 Xunta de Galicia; ED431D 2017/23 Xunta de Galicia; ED431C 2018/49 Xunta de Galicia; ED431G 2019/01

Presented at the 4th XoveTIC Conference, A Coruña, Spain, 7–8 October 2021. [Abstract] Transcription Factors (TFs) are proteins that regulate the expression of genes by binding to their promoter regions. There is great interest in understanding in which regions TFs will bind to the DNA sequence of an organism and the possible genetic implications that this entails. Occasionally, the sequence patterns (motifs) that a TF binds are not well defined. In this work, machine learning (ML) models were applied to TF binding data from ChIP-seq experiments. The objective was to detect patterns in TF binding regions that involved structural (DNAShapeR) and compositional (kmers) characteristics of the DNA sequence. After the application of random forest and Glmnet ML techniques with both internal and external validation, it was observed that two types of generated descriptors (HelT and tetramers) were significantly better than the others in terms of prediction, achieving values of more than 90%. This work has received financial support from the Xunta de Galicia and the European Union (European Social Fund (ESF)). This project was also supported by the General Directorate of Culture, Education and University Management of Xunta de Galicia (Ref. ED431G/01, ED431D 2017/16). Xunta de Galicia; ED431G/01 Xunta de Galicia; ED431D 2017/16

The Zika virus can induce a disruptive sequence in the fetal brain and is manifested mainly by microcephaly. Knowledge gaps still exist as to whether the virus can cause minor disorders that are perceived later on during the first years of life in children who are exposed but are asymptomatic at birth. In this case series, we describe the outcomes related to neurodevelopment through the neurological assessment of 26 non-microcephalic children who had intrauterine exposure to Zika virus. Children were submitted for neurological examinations and Bayley Scales-III (cognition, language, and motor performance). The majority (65.4%) obtained satisfactory performance in neurodevelopment. The most impaired domain was language, with 30.7% impairment. Severe neurological disorders occurred in five children (19.2%) and these were spastic hemiparesis, epilepsy associated with congenital macrocephaly (Zika and human immunodeficiency virus), two cases of autism (one exposed to Zika and Toxoplasma gondii) and progressive sensorineural hearing loss (GJB2 mutation). We concluded that non-microcephalic children with intrauterine exposure to Zika virus, in their majority, had achieved satisfactory performance in all neurodevelopmental domains. One third of the cases had some impairment, but the predominant group had mild alterations, with low occurrence of moderate to severe disorders, similar to other studies in Brazil.

The epidemic transmission of Zika virus (ZIKV) in Brazil has been identified as a cause of microcephaly and other neurological malformations in the babies of ZIKV-infected women. The frequency of adverse outcomes of Zika virus infection (ZIKVi) in pregnancy differs depending on the characteristics of exposure to infection, the time of recruitment of research participants, and the outcomes to be observed. This study provides a descriptive analysis&mdash, from the onset of symptoms to delivery&mdash, of a cohort registered as having maternal ZIKVi in pregnancy, from November 2015 to December 2016. Suspected cases were registered at a referral center for infectious and tropical diseases in Manaus, in the Amazonian region of Brazil. Of 834 women notified, 762 women with confirmed pregnancies were enrolled. Reverse-transcriptase polymerase chain reaction (RT-PCR) confirmed ZIKVi in 42.3% of the cohort. In 35.2% of the cohort, ZIKV was the sole infection identified. Severe adverse pregnancy outcomes (miscarriage, stillbirth, or microcephaly) were observed in both RT-PCR ZIKV-positive (5.0%) and ZIKV-negative (1.8%) cases (RR 3.1, 95% IC 1.4&ndash, 7.3, p &lt, 0.05), especially during the first trimester of pregnancy (RR 6.2, 95% IC 2.3&ndash, 16.5, 0.001). Although other infectious rash diseases were observed in the pregnant women in the study, having confirmed maternal ZIKVi was the most important risk factor for serious adverse pregnancy events.

Objective: to analyze AS before and 1 month (m) after bariatric surgery (BS), and search for pathophysiological mechanisms of changes (Δ). Methods: Forty-seven MO (72% women, 43% hypertensives, age 42.7±9.4 yr, BMI 42.2±5.4 Kg/m 2 , waist circumference 132.4±11.7 cm) were evaluated before and 1m after BS, with AS assessed by pulse-wave velocity (PWV), augmentation index at 75 beats/minute (AIx@75) and pulse pressure (PP) using a Mobile-O-Graph® device. 24h-ambulatory blood pressure (BP), RAAS components and several adipokines and inflammatory markers were also analyzed. Results: at 1m body weight (-13.6±4.32 Kg) and waist circumference (-9.2±5.3 cm) decreased (p Conclusions: there is a decrease in AS one month after BS in obese patients. These changes correlated with Δ in both BP and the renin-angiotensin aldosterone system. ( * ) Data shown as median [interquartile range]