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There are several needs of society, bringing some questions regarding the possibilities of projects that bring improvement of the community. Projects when implemented and that can bring individual and collective training and develop activities that meet the needs of interprofessional training of the social, economic and environmental sphere.

Metabolic programs contribute to hematopoietic stem and progenitor cell (HSPC) fate, but it is not known whether the metabolic regulation of protein synthesis controls HSPC differentiation. Here, we show that SLC7A1/CAT1-dependent arginine uptake and its catabolism to the polyamine spermidine control human erythroid specification of HSPCs via activation of the eukaryotic translation initiation factor 5A (eIF5A). eIF5A activity is dependent on its hypusination, a post-translational modification resulting from the conjugation of the aminobutyl moiety of spermidine to lysine. Notably, attenuation of hypusine synthesis in erythroid progenitors--by inhibition of deoxyhypusine synthase--abrogates erythropoiesis but not myeloid cell differentiation. Proteomic profiling reveals mitochondrial translation to be a critical target of hypusinated eIF5A and accordingly, progenitors with decreased hypusine activity exhibit diminished oxidative phosphorylation. This impacted pathway is critical for eIF5A-regulated erythropoiesis as interventions augmenting mitochondrial function partially rescue human erythropoiesis under conditions of attenuated hypusination. Levels of mitochondrial ribosomal proteins were especially sensitive to the loss of hypusine and we find that the ineffective erythropoiesis linked to haploinsufficiency of RPS14 in del(5q) myelodysplastic syndrome is associated with a diminished pool of hypusinated eIF5A. Moreover, patients with RPL11-haploinsufficient Diamond-Blackfan anemia as well as CD34+ progenitors with downregulated RPL11 exhibit a markedly decreased hypusination in erythroid progenitors, concomitant with a loss of mitochondrial metabolism. Thus, eIF5A-dependent protein synthesis regulates human erythropoiesis and our data reveal a novel role for RPs in controlling eIF5A hypusination in HSPC, synchronizing mitochondrial metabolism with erythroid differentiation.

Existe a influência da espiritualidade nas organizações, sendo este assunto mais amplamente abordado em países desenvolvidos, O presente artigo pretende analisar através de estudo bibliométrico o que já foi escrito até o presente momento em língua portuguesa sobre espiritualidade nas organizações, mapeando as publicações devido ao crescente interesse por os positivos resultados alcançados em produtividade e satisfação no ambiente de trabalho. Foram realizadas buscas em quinze dos principais sites de buscas de artigos acadêmicos utilizados no Brasil com as palavras chave “Espiritualidade nas organizações” dos quais foram encontrados conteúdo útil para a pesquisa atual em apenas cinco deles, que são: BDTD, EDUCATIONAL ADMINISTRATION ABSTRATIC, GOOGLE ACADEMIC, SPELL e SCIELO. Extraindo sessenta e nove (69) artigos analisados no período de 10 anos (2005-2015). Para tanto foi utilizado o estudo bibliométrico para as referidas analises quantitativas. Ao mesmo tempo em que se vê a importância do assunto nas mais diversas esferas organizacionais ainda há pouco estudo sobre o assunto em língua portuguesa, menos ainda pesquisas empíricas sobre o assunto. Fica claro que o devido tema está nos holofotes de pesquisadores do Brasil, e é fundamental que se produza artigos nesta perspectiva teórico-metológico.

In Lima, Peru, men who have sex with men (MSM) and transgender women (TW) are disproportionately affected by HIV. Patterns of sexual behavior vary by type of sexual partner, which has implications for the design of interventions to reduce HIV transmission within these groups. Among this population, we examine correlates of sex with each of four types of partners (main, casual, one-time, client) and condomless anal intercourse (CAI) with those partners. HIV-negative MSM and TW in Lima completed monthly questionnaires to indicate whether they had any of the four types of partners and whether they had CAI with those partners. Odds ratios were calculated using generalized estimating equations to identify correlates of being in different types of partnerships and CAI within those partnerships. In multivariate analysis of data from 1,831 MSM and TW over 14,792 study visits, CAI was most commonly reported with main partners, followed by casual partners, one-time partners, and clients. Presence of an alcohol use disorder (AUD) significantly increased the odds of CAI with all types of partners (main: OR 1.36 (95% CI 1.17–1.57); casual: 1.49 (1.27–1.75); one-time: 1.45 (1.22–1.72); client 1.52 (1.12–2.08)), while alcohol use in the last 30 days only increased the odds of CAI with main partners. Having one main partner decreased the odds of being in casual and one-time partnerships and of CAI in all types of partnerships. Interventions targeting AUDs and individuals with multiple sexual contacts could reduce CAI and HIV risk in this population.

Live fuel moisture content (LFMC) influences many fire-related aspects, including flammability, ignition, and combustion. In addition, fire spread models are highly sensitive to LFMC values. Despite its importance, LFMC estimation is still elusive due to its dependence on plant species traits, local conditions, and weather patterns. Although LFMC mapping from active synthetic aperture radar has increased over the past years, their utility for LFMC estimation needs further analysis to include additional areas characterized by different vegetation species and fire regimes. This study extended the current knowledge using medium spatial resolution (20 m) time series acquired by active (Sentinel-1) and passive (Sentinel-2) sensors. Our results show that optical-based LFMC estimation may achieve acceptable accuracy (R2 = 0.55, MAE = 15.1%, RMSE = 19.7%) at moderate (20 m) spatial resolution. When ancillary information (e.g., vegetation cover) was added, LFMC estimation improved (R2 = 0.63, MAE = 13.4%). Contrary to other studies, incorporating Sentinel-1 radar data did not provide for improved LFMC estimates, while the use of SAR data alone resulted in increased estimation errors (R2 = 0.28, MAE = 19%, RMSE = 25%). For increased fire risk scenarios (LFMC < 120%), estimation errors improved (MAE = 9.1%, RMSE = 11.8%), suggesting that direct LFMC retrieval from satellite data may be achieved with high temporal and spatial detail.

Background The ability to provide performance insights of various United States Medical Licensing Examination (USMLE) Step 1 assessments is of great importance to medical educators. Two custom pre-clerkship assessments used at the Kirk Kerkorian School of Medicine at the University of Nevada, Las Vegas (KSOM) are National Board of Medical Examiners (NBME)-derived end-of-semester final examinations and subject examinations. The authors sought to determine if performance on these custom assessments can provide feedback on a medical student's readiness to undertake the USMLE Step 1 examination. Methodology Deidentified student performance data were provided by institutional databases for the KSOM graduating class of 2023 (N = 60). Pearson correlation analyses were utilized to evaluate the strength of the correlation between USMLE Step 1 performance and NBME subject examinations versus NBME end-of-semester final examinations. Results The results indicated that the NBME end-of-semester final examinations have a statistically higher correlation to the USMLE Step 1 score than the majority of the individual NBME subject examinations. However, the mean NBME subject examination score (Semester 1: r = 0.53, p0.05; Semester 2: r = 0.58, p0.05) demonstrated significantly higher correlation to the USMLE Step 1 performance than the NBME end-of-semester final examination score for both Semesters 1 and 2 (Semester 1: r = 0.50, p0.05; Semester 2: r = 0.48, p0.05). Conclusions These results showed that the mean of the NBME subject examination score was a better metric to assess readiness for the USMLE Step 1 than the NBME end-of-semester final examinations. However, each NBME end-of-semester final examination score showed a better correlation than the majority of the NBME subject examinations.

Background X-linked dystonia parkinsonism is a generalized, progressive dystonia followed by parkinsonism with onset in adulthood and accompanied by striatal neurodegeneration. Causative mutations are located in a noncoding region of the TATA-box binding protein-associated factor 1 (TAF1) gene and result in aberrant splicing. There are 2 major TAF1 isoforms that may be decreased in symptomatic patients, including the ubiquitously expressed canonical cTAF1 and the neuronal-specific nTAF1. Objective The objective of this study was to determine the behavioral and transcriptomic effects of decreased cTAF1 and/or nTAF1 in vivo. Methods We generated adeno-associated viral (AAV) vectors encoding microRNAs targeting Taf1 in a splice-isoform selective manner. We performed intracerebroventricular viral injections in newborn mice and rats and intrastriatal infusions in 3-week-old rats. The effects of Taf1 knockdown were assayed at 4 months of age with evaluation of motor function, histology, and RNA sequencing of the striatum, followed by its validation. Results We report motor deficits in all cohorts, more pronounced in animals injected at P0, in which we also identified transcriptomic alterations in multiple neuronal pathways, including the cholinergic synapse. In both species, we show a reduced number of striatal cholinergic interneurons and their marker mRNAs after Taf1 knockdown in the newborn. Conclusion This study provides novel information regarding the requirement for TAF1 in the postnatal maintenance of striatal cholinergic neurons, the dysfunction of which is involved in other inherited forms of dystonia. © 2021 International Parkinson and Movement Disorder Society.

INTRODUCTION: The oral route of vaccination is pain- and needle-free and can induce systemic and mucosal immunity. However, gastrointestinal barriers and antigen degradation impose significant hurdles in the development of oral vaccines. Live attenuated viruses and bacteria can overcome these barriers but at the risk of introducing safety concerns. As an alternative, particles have been investigated for antigen protection and delivery, yet there are no FDA-approved oral vaccines based on particle-based delivery systems. Our objective was to discover underlying determinants that can explain the current inadequacies and identify paradigms that can be implemented in future for successful development of oral vaccines relying on particle-based delivery systems. AREAS COVERED: We reviewed literature related to the use of particles for oral vaccination and placed special emphasis on formulation characteristics and administration schedules to gain an insight into how these parameters impact production of antigen-specific antibodies in systemic and mucosal compartments. EXPERT OPINION: Despite the long history of vaccines, particle-based oral vaccination is a relative new field with the first study published in 1989. Substantial variability exists between different studies with respect to dosing schedules, number of doses, and the amount of vaccine per dose. Most studies have not used adjuvants in the formulations. Better standardization in vaccination parameters is required to improve comparison between experiments, and adjuvants should be used to enhance the systemic and mucosal immune responses and to reduce the number of doses, which will make oral vaccines more attractive.

While genetics evaluation is increasingly utilized in adult neurology patients, its usage and efficacy are not well characterized. Here, we report our experience with 1461 consecutive patients evaluated in an adult neurogenetics clinic at a large academic medical center between January 2015 and March 2020. Of the 1461 patients evaluated, 1215 patients were referred for the purposes of identifying a genetic diagnosis for an undiagnosed condition, 90.5% of whom underwent genetic testing. The modalities of genetic testing utilized varied across referral diagnostic categories, including a range of utilization of whole exome sequencing (WES) as an initial test in 13.9% of neuromuscular patients to 52.9% in white matter disorder patients. The usage of WES increased over time, from 7.7% of initial testing in 2015 to a peak of 27.3% in 2019. Overall, genetic testing yielded a causal genetic diagnosis in 30.7% of patients. This yield was higher in certain referring diagnosis categories, such as neuromuscular (39.0%) and epilepsy (29.8%). Our study demonstrates that evaluation at an adult neurogenetics referral center can yield diagnoses in a substantial fraction of patients. Additional research will be needed to determine optimal genetic testing strategies and cost effectiveness of adult neurogenetics evaluation.

Background: Observational studies in Parkinson’s disease (PD) have focused on relatively small numbers of research participants who are studied extensively. The Molecular Integration in Neurological Diagnosis Initiative at the University of Pennsylvania aims to characterize molecular and clinical features of PD in every patient in a large academic center. Objective: To determine the feasibility and interest in a global-capture biomarker research protocol. Additionally, to describe the clinical characteristics and GBA and LRRK2 variant carrier status among participants. Methods: All patients at UPenn with a clinical diagnosis of PD were eligible. Informed consent included options for access to the medical record, future recontact, and use of biosamples for additional studies. A blood sample and a completed questionnaire were obtained from participants. Targeted genotyping for four GBA and eight LRRK2 variants was performed, with plasma and DNA banked for future research. Results: Between September 2018 and December 2019, 704 PD patients were approached for enrollment; 652 (92.6%) enrolled, 28 (3.97%) declined, and 24 (3.41%) did not meet eligibility criteria. Median age was 69 (IQR 63_75) years, disease duration was 5.41 (IQR 2.49_9.95) years, and 11.10%of the cohort was non-white. Disease risk-associated variants in GBA were identified in 39 participants (5.98%) and in LRRK2 in 16 participants (2.45%). Conclusions: We report the clinical and genetic characteristics of PD patients in an all-comers, global capture protocol from an academic center. Patient interest in participation and yield for identification of GBA and LRRK2 mutation carriers is high, demonstrating feasibility of PD clinic-wide molecular characterization.

Background Similar to some monogenic forms of dystonia, levodopa-induced dyskinesia is a hyperkinetic movement disorder with abnormal nigrostriatal dopaminergic neurotransmission. Molecularly, it is characterized by hyper-induction of phosphorylation of extracellular signal-related kinase in response to dopamine in medium spiny neurons of the direct pathway. Objectives The objective of this study was to determine if mouse models of monogenic dystonia exhibit molecular features of levodopa-induced dyskinesia. Methods Western blotting and quantitative immunofluorescence was used to assay baseline and/or dopamine-induced levels of the phosphorylated kinase in the striatum in mouse models of DYT1, DYT6, and DYT25 expressing a reporter in dopamine D1 receptor-expressing projection neurons. Cyclic adenosine monophosphate (cAMP) immunoassay and adenylyl cyclase activity assays were also performed. Results In DYT1 and DYT6 models, blocking dopamine reuptake with cocaine leads to enhanced extracellular signal-related kinase phosphorylation in dorsomedial striatal medium spiny neurons in the direct pathway, which is abolished by pretreatment with the N-methyl-d-aspartate antagonist MK-801. Phosphorylation is decreased in a model of DYT25. Levels of basal and stimulated cAMP and adenylyl cyclase activity were normal in the DYT1 and DYT6 mice and decreased in the DYT25 mice. Oxotremorine induced increased abnormal movements in the DYT1 knock-in mice. Conclusions The increased dopamine induction of extracellular signal-related kinase phosphorylation in 2 genetic types of dystonia, similar to what occurs in levodopa-induced dyskinesia, and its decrease in a third, suggests that abnormal signal transduction in response to dopamine in the postsynaptic nigrostriatal pathway might be a point of convergence for dystonia and other hyperkinetic movement disorders, potentially offering common therapeutic targets. © 2021 International Parkinson and Movement Disorder Society.

O presente artigo tem como pauta o Governo Eletrônico e suas características práticas de aproximação e democratização entre o poder público e a sociedade, por meio do uso de tecnologias da informação. Para que tais práticas possam ocorrer e continuar evoluindo, os governos têm disponibilizado canais digitais, além da criação de decretos e leis, que pressionam os órgãos públicos a se adequarem ao cenário digital. Segundo o Departamento Nacional de Trânsito no ano de 2019 havia cerca de 73.844.088 usuários habilitados dos serviços dos Departamentos Estaduais de Trânsito em todo o território brasileiro (DENATRAN, em 2020). Ciente da relevância do impacto social e econômico para toda comunidade, vale verificar como os Departamentos Estaduais de Trânsito têm utilizado tecnologias da informação para possibilitar operacionalizar o governo eletrônico. Por esse motivo, o presente estudo objetiva analisar comparativamente os sites, aplicativos e Instagram dos Departamentos Estaduais de Trânsito dos estados de Alagoas e Sergipe, através do estudo das plataformas digitais e dados secundários.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by CAG trinucleotide repeat expansions in exon-1 of

A prática interdisciplinar é o processo de conexão possibilitando a integração dos conteúdos de diferentes disciplinas tornando o conhecimento mais significativo, mais amplo e mais útil ao aluno com o objetivo de dar sentido a eles. O tema proposto tem o objetivo de analisar a importância da prática interdisciplinar no curso de administração na Faculdade Adventista da Bahia. Para este artigo foi utilizado um instrumento de pesquisa usando uma abordagem quantitativa e qualitativa na aplicação do questionário. Analisando os resultados da pesquisa com alunos do curso de administração da Faculdade Adventista da Bahia. Verificou-se que, a prática interdisciplinar é de suma importânciapara a maioria dos alunos, porém, uma pequena parte afirma não saber o que é prática interdisciplinar. É importante ressaltar que na instituição de ensino tem oferta de uma matéria, que é específica para a área em questão, o que nos faz questionar os métodos de ensino. O objetivo do trabalho foi alcançado quando os resultados indicaram que 50% dos participantes afirmaram que a interdisciplinaridade é extremamente importante, porém, ainda resta uma lacuna que necessita de uma investigação mais aprofundada da Faculdade. A pesquisa mostra que 10,3% dos participantes afirmam não saber o que é prática interdisciplinar onde, na própria instituição tem uma matéria especifica chamada “pratica interdisciplinar”. Embora 48,3% dos participantes estejam afirmando está muito satisfeito com o seu desenvolvimento acadêmico, não podemos deixar passar despercebido os 10,3% dos participantes que não sabem o que é pratica interdisciplinar e talvez, irão se formar sem ao menos entender a sua contribuição e importância. Desse modo podemos afirmar que o objetivo da interdisciplinaridade educacional não está alcançando 100% de êxito no tocante aos alunos do curso de administração na Faculdade Adventista da Bahia.

Há evidências empíricas na literatura indicando que uma pessoa com uma mente empreendedora é alguém que tende a transformar conhecimento em riqueza e que a aprendizagem organizacional, portanto, proporciona maior inclinação parao empreendedorismo. É nesse sentido que o Movimento das Empresas Juniores (MEJ) no Brasil tem se engajado com a academia, com a finalidade de promover aprendizagem prática precoce. O objetivo deste estudo foi descrever as contribuições da aprendizagem organizacional para o fomento do empreendedorismo a partir de uma Empresa Júnior no Recôncavo da Bahia. Este estudo caracteriza-se metodologicamente por ter uma abordagem qualitativa de caráter descritivo e indutivo. A coleta de dados se deu por meio de uma entrevista semiestruturada, realizada em alguns casos via Google Meet e em outros casos presencialmente, com membros que possuem pelo menos seis meses de experiência na Empresa Júnior citada. Esses participantes são indivíduos entre 18 e 30 anos de idade, sendo homens e mulheres invariavelmente. A metodologia de análise adotada para inferência sobre os dados coletados foi a Análise de Conteúdo de Laurence Bardin. Os resultados indicaram que a aprendizagem organizacional é própria à existência da Empresa Junior, assim como, seus os membros tendem a se orientar para o mercado de trabalho mediante práticas empreendedoras. Ficou evidente que a aprendizagem organizacional e o empreendedorismo são elementos indissociáveis, que andam lado a lado, logo, concluímos que a aprendizagem organizacional proporciona maior inclinação para o empreendedorismo nos membros de uma Empresa Junior.

En el siguiente articulo, me propongo reconstruir algunos aspectos del lugar que la utopia ha ocupado en la tradicion de pensamiento marxista. Centrandome en dos momentos -las formulaciones originarias de Marx y Engels, y la consecuente reapropiacion de las mismas por parte de celebres filosofos marxistas del siglo XX-, me propongo rastrear el ambivalente lugar que ha ocupado la interpretacion de la utopia en algunos de los mas celebres aportes de pensamiento marxista.

Metabolic programs contribute to hematopoietic stem and progenitor cell (HSPC) fate but it is not known whether the metabolic regulation of protein synthesis controls HSPC differentiation. We discovered that SLC7A1/CAT1-dependent arginine uptake and its catabolism to spermidine control the erythroid specification of HSPCs via activation of eukaryotic translation initiation factor 5A (eIF5A). eIF5A activity is dependent on the metabolism of spermidine to hypusine and inhibiting hypusine synthesis abrogates erythropoiesis and diverts EPO-stimulated HSPCs to a myeloid fate. Proteomic profiling reveals mitochondrial translation to be a critical target of hypusinated eIF5A and induction of mitochondrial function partially rescues erythropoiesis in the absence of hypusine. Within the hypusine network, ribosomal proteins are highly enriched and we identify defective eIF5A hypusination in erythroid pathologies caused by abnormal ribosome biogenesis. Thus, eIF5A-dependent protein synthesis is critical in the branching of erythro-myeloid differentiation and attenuated eIF5A activity characterizes ribosomal protein-linked disorders of ineffective erythropoiesis.

Background: Huntington’s Disease Society of America Centers of Excellence (HDSA COEs) are primary hubs for Huntington’s disease (HD) research opportunities and accessing new treatments. Data on the extent to which HDSA COEs are accessible to individuals with HD, particularly those older or disabled, are lacking. Objective: To describe persons with HD in the U.S. Medicare program and characterize this population by proximity to an HDSA COE. Methods: We conducted a cross-sectional study of Medicare beneficiaries ages ≥65 with HD in 2017. We analyzed data on benefit entitlement, demographics, and comorbidities. QGis software and Google Maps Interface were employed to estimate the distance from each patient to the nearest HDSA COE, and the proportion of individuals residing within 100 miles of these COEs at the state level. Results: Among 9,056 Medicare beneficiaries with HD, 54.5% were female, 83.0% were white; 48.5% were ≥65 years, but 64.9% originally qualified for Medicare due to disability. Common comorbidities were dementia (32.4%) and depression (35.9%), and these were more common in HD vs. non-HD patients. Overall, 5,144 (57.1%) lived within 100 miles of a COE. Race/ethnicity, sex, age, and poverty markers were not associated with below-average proximity to HDSA COEs. The proportion of patients living within 100 miles of a center varied from 90% (7 states). Most underserved states were in the Mountain and West Central divisions. Conclusion: Older Medicare beneficiaries with HD are frequently disabled and have a distinct comorbidity profile. Geographical, rather than sociodemographic factors, define the HD population with limited access to HDSA COEs.

The globally accepted surgical strategy in glioblastomas is removing the enhancing tumor. However, the peritumoral region harbors infiltration areas responsible for future tumor recurrence. This study aimed to evaluate a predictive model that identifies areas of future recurrence using a voxel-based radiomics analysis of magnetic resonance imaging (MRI) data. This multi-institutional study included a retrospective analysis of patients diagnosed with glioblastoma who underwent surgery with complete resection of the enhancing tumor. Fifty-five patients met the selection criteria. The study sample was split into training (N = 40) and testing (N = 15) datasets. Follow-up MRI was used for ground truth definition, and postoperative structural multiparametric MRI was used to extract voxel-based radiomic features. Deformable coregistration was used to register the MRI sequences for each patient, followed by segmentation of the peritumoral region in the postoperative scan and the enhancing tumor in the follow-up scan. Peritumoral voxels overlapping with enhancing tumor voxels were labeled as recurrence, while non-overlapping voxels were labeled as nonrecurrence. Voxel-based radiomic features were extracted from the peritumoral region. Four machine learning-based classifiers were trained for recurrence prediction. A region-based evaluation approach was used for model evaluation. The Categorical Boosting (CatBoost) classifier obtained the best performance on the testing dataset with an average area under the curve (AUC) of 0.81 ± 0.09 and an accuracy of 0.84 ± 0.06, using region-based evaluation. There was a clear visual correspondence between predicted and actual recurrence regions. We have developed a method that accurately predicts the region of future tumor recurrence in MRI scans of glioblastoma patients. This could enable the adaptation of surgical and radiotherapy treatment to these areas to potentially prolong the survival of these patients.

Nowadays, the study of cell metabolism is a hot topic in cancer research. Many studies have used 2D conventional cell cultures for their simplicity and the facility to infer mechanisms. However, the limitations of bidimensional cell cultures to recreate architecture, mechanics, and cell communication between tumor cells and their environment, have forced the development of other more realistic in vitro methodologies. Therefore, the explosion of 3D culture techniques and the necessity to reduce animal experimentation to a minimum has attracted the attention of researchers in the field of cancer metabolism. Here, we revise the limitations of actual culture models and discuss the utility of several 3D culture techniques to resolve those limitations.

Prostate cancer is the second leading cause of cancer in men across the globe. The prostate gland accounts for some unique glycolytic metabolic characteristics, which causes the metabolic features of prostate tumor initiation and progression to remain poorly characterized. The mitochondrial superoxide dismutase (SOD2) is one of the major redox metabolism regulators. This study points out SOD2 as one major regulator for both redox and glycolytic metabolism in prostate cancer. SOD2 overexpression increases glucose transporter GLUT-1 and glucose uptake. This is not an insulin-mediated effect and seems to be sex-dependent, being present in male mice only. This event concurs with a series of substantial metabolic rearrangements at cytoplasmic and mitochondrial level. A concomitant decrease in glycolytic and pentose phosphate activity, and an increase in electron transfer in the mitochondrial electronic chain, were observed. The Krebs Cycle is altered to produce amino-acid intermediates by decreasing succinate dehydrogenase. This in turn generates a 13-fold increase in the oncometabolite succinate. The protein energy sensor AMPK is decreased at basal and phosphorylated levels in response to glucose deprivation. Finally, preliminary results in prostate cancer patients indicate that glandular areas presenting high levels of SOD2 show a very strong correlation with GLUT-1 protein levels (R2 = 0.287 p-value < 0.0001), indicating that in patients there may exist an analogous phenomenon to those observed in cell culture and mice.

RNA interference (RNAi) for spinocerebellar ataxia type 1 can prevent and reverse behavioral deficits and neuropathological readouts in mouse models, with safety and benefit lasting over many months. The RNAi trigger, expressed from adeno-associated virus vectors (AAV.miS1), also corrected misregulated microRNAs (miRNA) such as miR150. Subsequently, we showed that the delivery method was scalable, and that AAV.miS1 was safe in short-term pilot nonhuman primate (NHP) studies. To advance the technology to patients, investigational new drug (IND)-enabling studies in NHPs were initiated. After AAV.miS1 delivery to deep cerebellar nuclei, we unexpectedly observed cerebellar toxicity. Both small-RNA-seq and studies using AAVs devoid of miRNAs showed that this was not a result of saturation of the endogenous miRNA processing machinery. RNA-seq together with sequencing of the AAV product showed that, despite limited amounts of cross-packaged material, there was substantial inverted terminal repeat (ITR) promoter activity that correlated with neuropathologies. ITR promoter activity was reduced by altering the miS1 expression context. The surprising contrast between our rodent and NHP findings highlight the need for extended safety studies in multiple species when assessing new therapeutics for human application.

Smart Building is essential to advance towards more comfortable and sustainable cities. However, existing Building Management Systems (BMS) are proprietary non-interoperable solutions based on automatic operations configured by the users. These BMS can not control intelligently current and future buildings with highly heterogeneous legacy appliances and equipment including renewable energy generation, storage, e-vehicles charging points among others. In order to achieve it, this paper proposes an interoperable and intelligent architecture based on recent ICT technologies such as Internet of Things, Artificial Intelligence and Cybersecurity Protocols. This architecture provides five main innovations such as adapt-&-play hardware integration, standardised multi-systems interoperability, building/human behaviours prediction, security/privacy protection and smart services provision for increasing building energy-efficiency, occupants’ well-being and grid flexibility. To evaluate the proposed architecture, five diverse European pilots have been proposed. Specifically, this paper presents the Spanish pilot with multiple heterogeneous equipment and systems that will be employed to demonstrate the impact of the proposed architecture.

Producción Científica, Radiomics, in combination with artificial intelligence, has emerged as a powerful tool for the development of predictive models in neuro-oncology. Our study aims to find an answer to a clinically relevant question: is there a radiomic profile that can identify glioblastoma (GBM) patients with short-term survival after complete tumor resection? A retrospective study of GBM patients who underwent surgery was conducted in two institutions between January 2019 and January 2020, along with cases from public databases. Cases with gross total or near total tumor resection were included. Preoperative structural multiparametric magnetic resonance imaging (mpMRI) sequences were pre-processed, and a total of 15,720 radiomic features were extracted. After feature reduction, machine learning-based classifiers were used to predict early mortality (

Erythroblast maturation in mammals is dependent on organelle clearance throughout terminal erythropoiesis. We studied the role of the outer mitochondrial membrane protein voltage-dependent anion channel-1 (VDAC1) in human terminal erythropoiesis. We show that short hairpin (shRNA)-mediated downregulation of VDAC1 accelerates erythroblast maturation. Thereafter, erythroblasts are blocked at the orthochromatic stage, exhibiting a significant decreased level of enucleation, concomitant with an increased cell death. We demonstrate that mitochondria clearance starts at the transition from basophilic to polychromatic erythroblast, and that VDAC1 downregulation induces the mitochondrial retention. In damaged mitochondria from non-erythroid cells, VDAC1 was identified as a target for Parkin-mediated ubiquitination to recruit the phagophore. Here, we showed that VDAC1 is involved in phagophore’s membrane recruitment regulating selective mitophagy of still functional mitochondria from human erythroblasts. These findings demonstrate for the first time a crucial role for VDAC1 in human erythroblast terminal differentiation, regulating mitochondria clearance.