Artificial Neural Networks Manipulation Server: Research on the Integration of Databases and Artificial Neural Networks

The final publication is available at Springer via http://dx.doi.org/10.1007/s005210200011This paper proposes a new whole and distributed integration approach between Artificial Neural Networks (ANNs) and Databases (DBs) taking into account the different stages of the former’s lifecycle (training, test and running). The integration architecture which has been developed consists of an ANN Manipulation Server (AMS) based on a client-server approach, which improves the ANNs’ manipulation and experimentation capabilities considerably, and also those of their training and test sets, together with their modular reuse among possibly remote applications. Moreover, the chances of integrating ANNs and DBs are analysed, proposing a new level of integration which improves the integration features considerably. This level has not been contemplated yet at full reach in any of the commercial or experimental tools analysed up to the present date. Finally, the application of the integration architecture which has been developed to the specific domain of Environmental Impact Assessments (EIAs) is studied. Thus, the versatility and efficacy of that architecture for developing ANNs is tested. The enormous complexity of the functioning of the patterns which rule the environment’s behaviour, and the great number of variables involved, make it the ideal domain for experimenting on the application of ANNs together with DBs

Recombinant human leptin treatment in genetic lipodystrophic syndromes: the long-term Spanish experience

Lipodystrophies are a group of diseases mainly characterized by a loss of adipose tissue and frequently associated with insulin resistance, hypertriglyceridemia, and hepatic steatosis. In uncommon lipodystrophies, these complications frequently are difficult to control with conventional therapeutic approaches. This retrospective study addressed the effectiveness of recombinant methionyl leptin (metreleptin) for improving glucose metabolism, lipid profile, and hepatic steatosis in patients with genetic lipodystrophic syndromes. We studied nine patients (five females and four males) with genetic lipodystrophies [seven with Berardinelli-Seip syndrome, one with atypical progeroid syndrome, and one with type 2 familial partial lipodystrophy (FPLD)]. Six patients were children under age 9 years, and all patients had baseline triglycerides levels >2.26 mmol/L and hepatic steatosis; six had poorly controlled diabetes mellitus. Metreleptin was self-administered subcutaneously daily at a final dose that ranged between 0.05 and 0.24 mg/(kg day) [median: 0.08 mg/(kg day)] according to the body weight. The duration of treatment ranged from 9 months to 5 years, 9 months (median: 3 years). Plasma glucose, hemoglobin A1c (Hb A1c), lipid profile, plasma insulin and leptin, and hepatic enzymes were evaluated at baseline and at least every 6 months. Except for the patient with FPLD, metreleptin replacement significantly improved metabolic control (Hb A1c: from 10.4 to 7.1 %, p < 0.05). Plasma triglycerides were reduced 76 % on average, and hepatic enzymes decreased more than 65 %. This study extends knowledge about metreleptin replacement in genetic lipodystrophies, bearing out its effectiveness for long periods of time

Multiple Local and Recent Founder Effects of TGM1 in Spanish Families

<div><h3>Background</h3><p>Mutations in the <em>TGM1</em> gene encoding transglutaminase 1 are a major cause of autosomal recessive congenital ichthyosis. In the Galician (NW Spain) population, three mutations, c.2278C>T, c.1223_1227delACAC and c.984+1G>A, were observed at high frequency, representing ∼46%, ∼21% and ∼13% of all <em>TGM1</em> gene mutations, respectively. Moreover, these mutations were reported only once outside of Galicia, pointing to the existence of historical episodes of local severe genetic drift in this region.</p> <h3>Methodology/Principal Findings</h3><p>In order to determine whether these mutations were inherited from a common ancestor in the Galician population, and to estimate the number of generations since their initial appearance, we carried out a haplotype-based analysis by way of genotyping 21 SNPs within and flanking the <em>TGM1</em> gene and 10 flanking polymorphic microsatellite markers spanning a region of 12 Mb. Two linkage disequilibrium based methods were used to estimate the time to the most recent common ancestor (TMRCA), while a Bayesian-based procedure was used to estimate the age of the two mutations. Haplotype reconstruction from unphased genotypes of all members of the affected pedigrees indicated that all carriers for each of the two mutations harbored the same haplotypes, indicating common ancestry.</p> <h3>Conclusions/Significance</h3><p>In good agreement with the documentation record and the census, both mutations arose between 2,800–2,900 years ago (y.a.), but their TMRCA was in the range 600–1,290 y.a., pointing to the existence of historical bottlenecks in the region followed by population growth. This demographic scenario finds further support on a Bayesian Coalescent Analysis based on <em>TGM1</em> haplotypes that allowed estimating the occurrence of a dramatic reduction of effective population size around 900–4,500 y.a. (95% highest posterior density) followed by exponential growth.</p> </div

Meta-GWAS identifies the heritability of acute radiation-induced toxicities in head and neck cancer

Background and purpose: We aimed to the genetic components and susceptibility variants associated with acute radiation-induced toxicities (RITs) in patients with head and neck cancer (HNC). Materials and methods: We performed the largest meta-GWAS of seven European cohorts (n = 4,042). Patients were scored weekly during radiotherapy for acute RITs including dysphagia, mucositis, and xerostomia. We analyzed the effect of variants on the average burden (measured as area under curve, AUC) per each RIT, and standardized total average acute toxicity (STATacute) score using a multivariate linear regression. We tested suggestive variants (p < 1.0x10-5) in discovery set (three cohorts; n = 2,640) in a replication set (four cohorts; n = 1,402). We meta-analysed all cohorts to calculate RITs specific SNP-based heritability, and effect of polygenic risk scores (PRSs), and genetic correlations among RITS. Results: From 393 suggestive SNPs identified in discovery set; 37 were nominally significant (preplication < 0.05) in replication set, but none reached genome-wide significance (pcombined < 5 × 10-8). In-silico functional analyses identified “3′-5'-exoribonuclease activity” (FDR = 1.6e-10) for dysphagia, “inositol phosphate-mediated signalling” for mucositis (FDR = 2.20e-09), and “drug catabolic process” for STATacute (FDR = 3.57e-12) as the most enriched pathways by the RIT specific suggestive genes. The SNP-based heritability (±standard error) was 29 ± 0.08 % for dysphagia, 9 ± 0.12 % (mucositis) and 27 ± 0.09 % (STATacute). Positive genetic correlation was rg = 0.65 (p = 0.048) between dysphagia and STATacute. PRSs explained limited variation of dysphagia (3 %), mucositis (2.5 %), and STATacute (0.4 %). Conclusion: In HNC patients, acute RITs are modestly heritable, sharing 10 % genetic susceptibility, when PRS explains < 3 % of their variance. We identified numerus suggestive SNPs, which remain to be replicated in larger studies

Large-Scale Meta-GWAS Reveals Common Genetic Factors Linked to Radiation-Induced Acute Toxicities across Cancers

BACKGROUND: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity (RIT) across four cancer types (prostate, head and neck, breast, and lung).METHODS: A GWAS meta-analysis was performed using 19 cohorts including 12,042 patients. Acute standardized total average toxicity (rSTATacute) was modelled using a generalized linear regression model for additive effect of genetic variants adjusted for demographic and clinical covariates. LD score regression estimated shared SNP-based heritability of rSTATacute in all patients and for each cancer type.RESULTS: Shared SNP-based heritability of STATacute among all cancer types was estimated at 10% (se = 0.02), and was higher for prostate (17%, se = 0.07), head and neck (27%, se = 0.09), and breast (16%, se = 0.09) cancers. We identified 130 suggestive associated SNPs with rSTATacute (5.0x10-8&lt;P-value&lt;1.0x10-5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size -0.17; P-value=1.7x10-7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified 'RNA splicing via endonucleolytic cleavage and ligation' (P = 5.1 x10-6, Pcorrected =0.079) as the top gene set associated with rSTATacute among all patients. In-silico gene expression analysis showed the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed Pcorrected=0.004; sun exposed Pcorrected=0.026).CONCLUSIONS: There is shared SNP-based heritability for acute RIT across and within individual cancer sites. Future meta-GWAS among large radiotherapy patient cohorts are worthwhile to identify the common causal variants for acute radiotoxicity across cancer types.</p

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Precariedad, exclusión social y diversidad funcional (discapacidad): lógicas y efectos subjetivos del sufrimiento social contemporáneo (II). Innovación docente en Filosofía

El PIMCD "Precariedad, exclusión social y diversidad funcional (discapacidad): lógicas y efectos subjetivos del sufrimiento social contemporáneo (II). Innovación docente en Filosofía" se ocupa de conceptos generalmente eludidos por la tradición teórica (contando como núcleos aglutinantes los de la precariedad laboral, la exclusión social y diversidad funcional o discapacidad), cuyo análisis propicia nuevas prácticas en la enseñanza universitaria de filosofía, adoptando como meta principal el aprendizaje centrado en el estudiantado, el diseño de nuevas herramientas de enseñanza y el fomento de una universidad inclusiva. El proyecto cuenta con 26 docentes de la UCM y otros 28 docentes de otras 17 universidades españolas (UV, UNED, UGR, UNIZAR, UAH, UC3M, UCA, UNIOVI, ULL, EHU/UPV, UA, UAM, Deusto, IFS/CSIC, UCJC, URJC y Univ. Pontificia de Comillas), que permitirán dotar a las actividades programadas de un alcance idóneo para consolidar la adquisición de competencias argumentativas y dialécticas por parte de lxs estudiantes implicados en el marco de los seminarios previstos. Se integrarán en el PIMCD, aparte de PDI, al menos 26 estudiantes de máster y doctorado de la Facultad de Filosofía, a lxs que acompañarán durante el desarrollo del PIMCD 4 Alumni de la Facultad de Filosofía de la UCM, actualmente investigadores post-doc y profesorxs de IES, cuya experiencia será beneficiosa para su introducción en la investigación. Asimismo, el equipo cuenta con el apoyo de varixs profesorxs asociadxs, que en algunos casos son también profesores de IES. Varixs docentes externos a la UCM participantes en el PIMCD poseen una dilatada experiencia en la coordinación de proyectos de innovación de otras universidades, lo que redundará en beneficio de las actividades a desarrollar. La coordinadora y otrxs miembros del PIMCD pertenecen a la Red de Innovación Docente en Filosofia (RIEF), puesta en marcha desde la Universitat de València (http://rief.blogs.uv.es/encuentros-de-la-rief/), a la que mantendremos informada de las actividades realizadas en el proyecto. Asimismo, lxs 6 miembros del PAS permitirán difundir debidamente las actividades realizadas en el PIMCD entre lxs estudiantes Erasmus IN del curso 2019/20 en la Facultad de Filosofía, de la misma manera que orientar en las tareas de maquetación y edición que puedan ser necesarias de cara a la publicación de lxs resultados del PIMCD y en las tareas de pesquisa bibliográfica necesarias para el desarrollo de los objetivos propuestos. Han manifestado su interés en los resultados derivados del PIMCD editoriales especializadas en la difusión de investigaciones predoctorales como Ápeiron y CTK E-Books

Recomendaciones de uso adecuado de pruebas y suplementos de vitamina D en población general

Nos últimos anos, houbo un aumento no número de determinacións analíticas da vitamina D (VitD) e no número de suplementos de VitD prescritos. Esta situación foi causada pola suposición dunha asociación entre os niveis non óptimos de VitD e resultados adversos en varias condicións clínicas, diferentes das relacionadas coa deficiencia (raquitismo e osteomalacia). Esta publicación recolle unha revisión sistemática sobre o uso adecuado da vitD e unhas recomendacións por consenso dun grupo multidisciplinar de profesionais clínicos, que serían: Non é necesario determinar os niveis de vitamina D en adultos sans asintomáticos e sen factores de risco para o déficit de VitD. A suplementación con vitamina D, neste grupo de poboación (sans asintomáticos), non demostrou beneficios independientemente dos niveis de VitD. Porén, a suplementación poderíase considerar en mairoes de 70 anos residentes en institucións sen necesidade de determinación.En los últimos años, hubo un aumento en el número de determinaciones analíticas de la vitamina D (VitD) y en el número de suplementos de VitD prescritos. Esta situación fue causada por la suposición de una asociación entre los niveles no óptimos de VitD y resultados adversos en varias condiciones clínicas, diferentes de las relacionadas con la deficiencia (raquitismo y osteomalacia). Esta publicación recoge una revisión sistemática sobre el uso adecuado de vitD y unas recomendaciones por consenso de un grupo multidisciplinar de profesionales clínicos, que serían: No es necesario determinar los niveles de vitamina D en adultos sanos asintomáticos y sin factores de riesgo para el déficit de VitD. La suplementación con vitamina D, en este grupo de población (sanos asintomáticos), no demostró beneficios independientemente de los niveles de VitD. Por ello, la suplementación podría considerarse en mayores de 70 años residentes en instituciones sin necesidade de determinación.MInisterio de Sanida