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Abstract Background Fragile X syndrome, the major cause of inherited intellectual disability among men, is due to deficiency of the synaptic functional regulator FMR1 protein (FMRP), encoded by the FMRP translational regulator 1 (FMR1) gene. FMR1 alternative splicing produces distinct transcripts that may consequently impact FMRP functional roles. In transcripts without exon 14 the translational reading frame is shifted. For deepening current knowledge of the differential expression of Fmr1 exon 14 along the rat nervous system development, we conducted a descriptive study employing quantitative RT-PCR and BLAST of RNA-Seq datasets. Results We observed in the rat forebrain progressive decline of total Fmr1 mRNA from E11 to P112 albeit an elevation on P3; and exon-14 skipping in E17–E20 with downregulation of the resulting mRNA. We tested if the reduced detection of messages without exon 14 could be explained by nonsense-mediated mRNA decay (NMD) vulnerability, but knocking down UPF1, a major component of this pathway, did not increase their quantities. Conversely, it significantly decreased FMR1 mRNA having exon 13 joined with either exon 14 or exon 15 site A. Conclusions The forebrain in the third embryonic week of the rat development is a period with significant skipping of Fmr1 exon 14. This alternative splicing event chronologically precedes a reduction of total Fmr1 mRNA, suggesting that it may be part of combinatorial mechanisms downregulating the gene’s expression in the late embryonic period. The decay of FMR1 mRNA without exon 14 should be mediated by a pathway different from NMD. Finally, we provide evidence of FMR1 mRNA stabilization by UPF1, likely depending on FMRP.

Large-scale transcriptome and methylome data analyses obtained by high-throughput technologies have been enabling the identification of novel imprinted genes. We investigated genome-wide DNA methylation patterns in multiple human tissues, using a high-resolution microarray to uncover hemimethylated CpGs located in promoters overlapping CpG islands, aiming to identify novel candidate imprinted genes. Using our approach, we recovered ~30% of the known human imprinted genes, and a further 168 candidates were identified, 61 of which with at least three hemimethylated CpGs shared by more than two tissue types. Thirty-four of these candidate genes are members of the protocadherin cluster on 5q31.3; in mice, protocadherin genes have non-imprinted random monoallelic expression, which might also be the case in humans. Among the remaining 27 genes, ZNF331 was recently validated as an imprinted gene, and six of them have been reported as candidates, supporting our prediction. Five candidates (CCDC166, ARC, PLEC, TONSL, and VPS28) map to 8q24.3, and might constitute a novel imprinted cluster. Additionally, we performed a comprehensive compilation of known human and mice imprinted genes from literature and databases, and a comparison among high-throughput imprinting studies in humans. The screening for hemimethylated CpGs shared by multiple human tissues, together with the extensive review, appears to be a useful approach to reveal candidate imprinted genes.

Introduction: Phyllodes tumors are rare fibroepithelial neoplasms. They represent less than 0.5–1% of all primary breast tumors and their presentation is even rarer in children. Case description: A 15-year-old female with Autism Spectrum Disorder (ASD) was seen in the outpatient surgery clinic due to bilateral breast masses. She underwent core-needle aspiration. biopsy of both masses and the results were suspicious of fibroadenomas. Two days later the patient presented to the emergency room with ulceration and bleeding from the left breast mass. She was scheduled for an urgent nipple-sparing mastectomy, which was uneventful. The pathology revealed a multifocal, aggressive type tumor with moderate stromal cellularity, moderate stromal atypia and high mitotic index, corresponding to a borderline phyllodes tumor. Based on this result, she underwent an elective right nipple-sparing mastectomy. The pathology of the right breast mass was similar to the left breast mass. Conclusion: Core-needle aspiration biopsy is not reliable for the diagnosis of phyllodes tumor. If a phyllodes tumor is diagnoses in one breast, a contralateral breast mass should be considered a phyllodes tumor until proven otherwise.

Two different hybrid nanosystems are prepared by loading highly crystalline, monodisperse magnetite nanocubes (MNCs) with phosphorescent Pt(II) complexes (PtCxs). One involves the encapsulation of the hydrophobic PtCx1 within an amphiphilic comb polymer (MNC@poly(maleic anhydride‐alt‐1‐octadecene) [PMAO]–PtCx1), whereas the other involves the direct binding of the hydrophilic PtCx2 to the surface of the MNC mediated by a ligand‐exchange procedure (MNC@OH–PtCx2). Both systems are evaluated as potential candidates for multimodal imaging in magnetic resonance imaging (MRI) and photoluminescence lifetime imaging micro(spectro)scopy (PLIM). PLIM measurements on agarose phantoms demonstrate significantly longer excited‐state lifetimes compared to the short‐lived autofluorescence of biological background. Additionally, both nanosystems perform as effective MRI contrast agents (CAs): the r2* values are 3–4 times higher than for the commercial CA ferucarbotran. MNC@PMAO–PtCx1 particles also cause significant increases in r2. While the ligand exchange procedure efficiently anchors PtCxs to the MNC surface, the polymeric encapsulation ensures higher colloidal stability, contributing to differences in PLIM and MRI outcomes. In these results, the successful integration of two complementary noninvasive imaging modalities within a single nanosystem is confirmed, serving as the impetus for further investigation of such systems as advanced multimodal–multiscale imaging agents with dual orthogonal readouts.

High dose-intensive or infusional intermediate-dose immunochemotherapy is highly effective treatment for Burkitt lymphoma irrespective of human immunodeficiency virus (HIV) infection. However, toxicities of these regimens are relevant, especially in older adults and elderly patients. The prospective multicenter BURKIMAB14 trial included four to six blocks of immunochemotherapy according to stage (localized: 1 and 2 non-bulky; advanced: 2 bulky, 3, 4) and age, with dose reduction in patients >55 years old. Dose-intensity of chemotherapy was reduced in patients ≤55 years old after achieving complete metabolic response (CMR). Their outcomes were compared with those of similar patients included in the former BURKIMAB08 trial, in which there was no dose reduction. CMR was attained in 86 of 107 (80%) patients (17/19 in localized stages and 69/88 in advanced stages). Patients from the BURKIMAB14 trial ≤55 years old showed similar overall survival (OS), fewer infections and cytopenias than patients from the BURKIMAB08 trial. Patients >55 years old had a significantly higher treatment- related mortality despite dose reduction of chemotherapy. With a median follow-up of 3.61 years the 4-year OS probability was 73% (range, 63-81%). Age (≤55 vs. >55 years) and stage (localized vs. advanced) had prognostic significance. No significant differences in OS were observed in HIV-positive versus HIV-negative patients. The results of BURKIMAB14 are similar to those of other dose-intensive immunochemotherapy trials. Age >55 years and advanced stage, but not HIV infection, were associated with poor survival. Dose reduction of chemotherapy in young adults in CMR is safe and does not impact outcomes (clinicaltrials gov. Identifier: NCT05049473).

In the last few years, Satellite Precipitation Estimates (SPE) have been increasingly used for rainfall estimation applications. Their validity and accuracy are influenced by several factors related to the location where the SPEs are applied. The objective of this study is to evaluate the performance of the Integrated Multisatellite Retrievals for Global Precipitation Measurement Version 06 Half-Hour Temporal Resolution (IMERG-FR V06 HH) for rainfall estimation, as well as to determine its relationships with the hourly and daily rain gauge network data in a semiarid region during 2019–2021. The methodology contemplates the temporality, elevation, rainfall intensity, and rain gauge density variables, carrying out a point-to-pixel analysis using continuous, (Bias, r, ME, and RMSE), categorical (POD, FAR, and CSI), and volumetric (VHI, VFAR, and VCSI) statistical metrics to understand the different behaviors between the rain gauge and IMERG-FR V06 HH data. IMERG-FR greatly underestimated the heavy rainfall events in values of −63.54 to −23.58 mm/day and −25.29 to −11.74 mm/30 min; however, it overestimates the frequency of moderate rain events (1 to 25 mm/day). At making the correlation (r) between the temporal scales, the monthly temporal resolution was the one that better relates the measured and estimated data, as well as reported r values of 0.83 and 0.85, where records at shorter durations in IMERG-FR do not detect them. The weakness of this system, according to the literature and confirmed by the research findings, in the case of hydrological phenomena, is that recording or estimating short durations is essential for the water project, and therefore, the placement of rain gauges. The 1902–2101 m.a.s.l. range elevation has the best behavior between the data with the lowest error and best detection ability, of which IMERG-FR tended to overestimate the rain at higher altitudes. Considering that the r for two automated rain gauges per IMERG-FR pixel density was 0.74, this indicates that the automated rain gauges versus IMERG-FR have a better data fit than the rain gauges versus IMERG-FR. The distance to centroid and climatic evaluations did not show distinctive differences in the performance of IMERG. These findings are useful to improve the IMERG-FR algorithms, guide users about its performance at semiarid plateau regions, and assist in the recording of data for hydrological projects.

Objetivos: identificar las características sociodemográficas; y analizar la asociación de las variables sociodemográficas a los sistemas funcionales relacionados con la cognición y el estado de ánimo/comportamiento de las personas mayores vinculadas a la Atención Domiciliaria. Método: investigación transversal, descriptiva, realizada con la participación de 108 ancianos vinculados a la Asistencia Domiciliaria en el municipio de Santa Maria- RS - Brasil. Se utilizó el cuestionario de datos sociodemográficos y el Índice de Vulnerabilidad Clínico Funcional IVCF-20. La asociación de variables se analizó mediante la prueba chi-cuadrado y la prueba de muestras independientes. Resultados: predominio de mujeres de edad avanzada; edad media 78,7 ± 9,3 años; y bajo nivel educativo e ingresos familiares entre 1 y 2 salarios mínimos. La morbilidad más frecuente fue la hipertensión arterial sistémica. No se encontraron asociaciones entre las variables sociodemográficas y los sistemas funcionales relacionados con la cognición y el estado de ánimo/comportamiento. Conclusión: se destaca la importancia de la planificación y las intervenciones en el entorno domiciliario.

Objectives: to identify the sociodemographic characteristics; and to analyze the association of sociodemographic variables with functional systems related to cognition and mood/behavior of elderly people linked to Home Care. Method: cross-sectional, descriptive research, carried out with the participation of 108 elderly people linked to Home Care in the city of Santa Maria - RS - Brazil. We used a questionnaire of sociodemographic data and the Clinical and Functional Vulnerability Index IVCF-20. The association of the variables was analyzed using the chi-square test and independent samples test. Results: predominance of elderly females; mean age 78.7 ± 9.3 years; and low education and family income between 1 and 2 minimum wages. The most frequent morbidity was systemic arterial hypertension. No associations were found between the sociodemographic variables and the functional systems regarding cognition and mood/behavior. Conclusion: the importance of planning and interventions in the home environment is highlighted.

Objetivos: identificar as características sociodemográficas; e analisar a associação das variáveis sociodemográficas aos sistemas funcionais referentes à cognição e humor/comportamento de idosos vinculados à Atenção Domiciliar. Método: pesquisa transversal, descritiva, realizada com a participação de 108 idosos vinculados à Atenção Domiciliar do município de Santa Maria- RS - Brasil. Utilizaram-se o questionário de dados sociodemográficos e o Índice de Vulnerabilidade Clínico Funcional IVCF-20. Analisou-se a associação das variáveis por meio do teste do qui-quadrado e teste de amostras independentes. Resultados: predomínio de idosos do sexo feminino; idade média de 78,7 ± 9,3 anos; e escolaridade baixa e renda familiar entre 1 e 2 salários-mínimos. A morbidade mais frequente foi a hipertensão arterial sistêmica. Não foram encontradas associações entre as variáveis sociodemográficas e os sistemas funcionais referentes à cognição e humor/comportamento. Conclusão: salienta-se a importância do planejamento e de intervenções no ambiente domiciliar.

Abstract Interferon lambda 4 (IFNλ4) has shown antiviral activity against RNA viruses, including some coronaviruses. Besides, genetic variants of IFNL4 can be predictive of the clearance of RNA viruses. However, little is known about the effect of these genetic variants on SARS-CoV-2 infection. In this study, we investigated whether there was a relationship of the rs12979860 polymorphism of IFNL4 with COVID-19. We found that the T allele of rs12979860 was overexpressed in COVID-19 patients with regard to the general population without this disease (36.16% vs. 26.40%, p = 6.4 × 10–4; OR 0.633 C vs T; 95% CI 0.487, 0.824), suggesting that this allele could be a risk factor for COVID-19. Accordingly, the CC genotype was significantly lower in COVID-19 patients compared to controls (37.85% vs. 55.51%, p = 8 × 10–5; OR 0.488; 95% CI 0.342, 0.698). These results were not affected by sex, age, and disease severity in patients with COVID-19. Our findings suggest that, like other infectious diseases caused by RNA viruses, genetic variants of IFNL4 can predispose to COVID-19. Confirmation of our results may contribute to better understanding the mechanisms of this disease.

Hepatoblastoma (HB) is a rare embryonal tumor, although it is the most common pediatric liver cancer. The aim of this study was to provide an accurate cytogenomic profile of this type of cancer, for which information in cancer databases is lacking. We performed an extensive literature review of cytogenetic studies on HBs disclosing that the most frequent copy number alterations (CNAs) are gains of 1q, 2/2q, 8/8q, and 20; and losses at 1p and 4q. Furthermore, the CNA profile of a Brazilian cohort of 26 HBs was obtained by array-CGH; the most recurrent CNAs were the same as shown in the literature review. Importantly, HBs from female patients, high-risk stratification tumors, tumors who developed in older patients (> 3 years at diagnosis) or from patients with metastasis and/or deceased carried a higher diversity of chromosomal alterations, specifically chromosomal losses at 1p, 4, 11q and 18q. In addition, we distinguished three major CNA profiles: no detectable CNA, few CNAs and tumors with complex genomes. Tumors with simpler genomes exhibited a significant association with the epithelial fetal subtype of HBs; in contrast, the complex genome group included three cases with epithelial embryonal histology, as well as the only HB with HCC features. A significant association of complex HB genomes was observed with older patients who developed high-risk tumors, metastasis, and deceased. Moreover, two patients with HBs exhibiting complex genomes were born with congenital anomalies. Together, these findings suggest that a high load of CNAs, mainly chromosomal losses, particularly losses at 1p and 18, increases the tendency to HB aggressiveness. Additionally, we identified six hot-spot chromosome regions most frequently affected in the entire group: 1q31.3q42.3, 2q23.3q37.3, and 20p13p11.1 gains, besides a 5,3 Mb amplification at 2q24.2q24.3, and losses at 1p36.33p35.1, 4p14 and 4q21.22q25. An in-silico analysis using the genes mapped to these six regions revealed several enriched biological pathways such as ERK Signaling, MicroRNAs in Cancer, and the PI3K-Akt Signaling, in addition to the WNT Signaling pathway; further investigation is required to evaluate if disturbances of these pathways can contribute to HB tumorigenesis. The analyzed gene set was found to be associated with neoplasms, abnormalities of metabolism/homeostasis and liver morphology, as well as abnormal embryonic development and cytokine secretion. In conclusion, we have provided a comprehensive characterization of the spectrum of chromosomal alterations reported in HBs and identified specific genomic regions recurrently altered in a Brazilian HB group, pointing to new biological pathways, and relevant clinical associations.

The complexity of assessing the irrigation performance of a solid-set sprinkler irrigation system implies analyzing factors of the sprinkler features, the spacing among sprinklers, the evaluation heights, the meteorological variables and the crop. In this research, a number of solid-set experiments with impact sprinklers were evaluated with different operating conditions and a number of models of irrigation uniformity (CUC) and losses due to drift and wind (WDEL) were assessed at different catch-can heights. Statistical analysis and predictive models were performed for each variable analyzed. The results showed that ND 5035 and SEN 4023 impact sprinklers that presented the lowest variability in water distributions patterns based on the standard deviations of the irrigation depth collected in the catch can (0.85 mm/h). These sprinklers had demonstrated the best CUC values (mean of 86%) with low WDEL averages (lower than 9%). Regarding the CUC analysis, there was a statistically significant difference in measuring the irrigation uniformity from 1 to 2 m catch-can height based on the analysis of 396 solid-set experiments of different research works. Future research could be focused on more experimental conditions analyzing the effects of the irrigation on the crop agronomic development and its yield.

Hepatoblastoma is a very rare embryonal liver cancer supposed to arise from the impairment of hepatocyte differentiation during embryogenesis. In this study, we investigated by exome sequencing the burden of somatic mutations in a cohort of 10 hepatoblastomas, including a congenital case. Our data disclosed a low mutational background and pointed out to a novel set of candidate genes for hepatoblastoma biology, which were shown to impact gene expression levels. Only three recurrently mutated genes were detected: CTNNB1 and two novel candidates, CX3CL1 and CEP164. A relevant finding was the identification of a recurrent mutation (A235G) in two hepatoblastomas at the CX3CL1 gene; evaluation of RNA and protein expression revealed upregulation of CX3CL1 in tumors. The analysis was replicated in two independents cohorts, substantiating that an activation of the CX3CL1/CX3CR1 pathway occurs in hepatoblastomas. In inflammatory regions of hepatoblastomas, CX3CL1/CX3CR1 were not detected in the infiltrated lymphocytes, in which they should be expressed in normal conditions, whereas necrotic regions exhibited negative labeling in tumor cells, but strongly positive infiltrated lymphocytes. Altogether, these data suggested that CX3CL1/CX3CR1 upregulation may be a common feature of hepatoblastomas, potentially related to chemotherapy response and progression. In addition, three mutational signatures were identified in hepatoblastomas, two of them with predominance of either the COSMIC signatures 1 and 6, found in all cancer types, or the COSMIC signature 29, mostly related to tobacco chewing habit; a third novel mutational signature presented an unspecific pattern with an increase of C>A mutations. Overall, we present here novel candidate genes for hepatoblastoma, with evidence that CX3CL1/CX3CR1 chemokine signaling pathway is likely involved with progression, besides reporting specific mutational signatures.

Nanocomposite engineering of biosensors, biomaterials, and flexible electronics demand a highly tunable synthesis of precursor materials to achieve enhanced or desired properties. However, this process remains limited due to the need for proper synthesis-property strategies. Herein, we report on the ability to synthesize chitosan-gold nanocomposite thin films (CS/AuNP) with tunable properties by chemically reducing HAuCl4 in chitosan solutions and different HAuCl4/sodium citrate molar relationships. The structure, electrical, and relaxation properties of nanocomposites have been investigated as a function of HAuCl4/sodium citrate molar relation. It was shown that gold particle size, conductivity, Vogel temperature (glass transition), and water content strongly depend upon HAuCl4/sodium citrate relationships. Two relaxation processes have been observed in nanocomposites; the α-relaxation process, related to a glass transition in wet CS/AuNP films, and the σ-relaxation related to the local diffusion process of ions in a disordered system. The ability to fine-tune both α- and σ-relaxations may be exploited in the proper design of functional materials for biosensors, biomaterials, and flexible electronics applications.

Abstract Molybdenum and tungsten are taken up by bacteria and archaea as their soluble oxyanions through high affinity transport systems belonging to the ATP-binding cassette (ABC) transporters. The component A (ModA/TupA) of these transporters is the first selection gate from which the cell differentiates between MoO4 2−, WO4 2− and other similar oxyanions. We report the biochemical characterization and the crystal structure of the apo-TupA from Desulfovibrio desulfuricans G20, at 1.4 Å resolution. Small Angle X-ray Scattering data suggests that the protein adopts a closed and more stable conformation upon ion binding. The role of the arginine 118 in the selectivity of the oxyanion was also investigated and three mutants were constructed: R118K, R118E and R118Q. Isothermal titration calorimetry clearly shows the relevance of this residue for metal discrimination and oxyanion binding. In this sense, the three variants lost the ability to coordinate molybdate and the R118K mutant keeps an extremely high affinity for tungstate. These results contribute to an understanding of the metal-protein interaction, making it a suitable candidate for a recognition element of a biosensor for tungsten detection.

Purpose: We report a rare case of a metastatic carcinoid tumor to the right lower lid masquerading as a chalazion. Observations: A 78-year-old Hispanic woman who presented with a 3-month history of a non-resolving chalazion on the right lower lid despite aggressive medical treatment. The patient had a history of noninfectious anterior uveitis and primary hepatic carcinoid tumor that was incidentally diagnosed during the initial uveitis work-up. The right lower eyelid lesion was biopsied and histological and immunopathological analysis revealed a well differentiated neuroendocrine tumor consistent with a carcinoid tumor. Conclusionand Importance: Neuroendocrine tumors should be considered as part of the differential diagnosis of focal, vascularized eyelid masses. To the authors best knowledge this is the first reported case of primary hepatic carcinoid tumor with metastasis to the eyelids. We also highlight the importance of pursuing a histopathologic diagnosis, in the setting of a non-resolving or recurrent chalazion. Keywords: Carcinoid tumor, Metastasis, Eyelid, Histopathology, Immunostaining, Chalazion

Hepatoblastoma is an embryonal liver tumor carrying few genetic alterations. We previously disclosed in hepatoblastomas a genome-wide methylation dysfunction, characterized by hypermethylation at specific CpG islands, in addition to a low-level hypomethylation pattern in non-repetitive intergenic sequences, in comparison to non-tumoral liver tissues, shedding light into a crucial role for epigenetic dysregulation in this type of cancer. To explore the underlying mechanisms possibly related to aberrant epigenetic modifications, we evaluated the expression profile of a set of genes engaged in the epigenetic machinery related to DNA methylation (DNMT1, DNMT3A, DNMT3B, DNMT3L, UHRF1, TET1, TET2, and TET3), as well as the 5-hydroxymethylcytosine (5hmC) global level. We observed in hepatoblastomas a general disrupted expression of these genes from the epigenetic machinery, mainly UHRF1, TET1, and TET2 upregulation, in association with an enrichment of 5hmC content. Our findings support a model of active demethylation by TETs in hepatoblastoma, probably during early stages of liver development, which in combination with UHRF1 overexpression would lead to DNA hypomethylation and an increase in overall 5hmC content. Furthermore, our data suggest that decreased 5hmC content might be associated with poor survival rate, highlighting a pivotal role of epigenetics in hepatoblastoma development and progression.

The homeobox NKX2 family of transcriptional factors has been shown to regulate fundamental developmental processes. Here, the authors show that NKX2-3 is a bona fideoncogenic driver in marginal-zone B-cell lymphoma and that it promotes lymphomagenesis by shaping lymphocyte dynamics and promoting BCR signalling.

The TupABC system is involved in the cellular uptake of tungsten and belongs to the ABC (ATP binding cassette)-type transporter systems. The TupA component is a periplasmic protein that binds tungstate anions, which are then transported through the membrane by the TupB component using ATP hydrolysis as the energy source (the reaction catalyzed by the ModC component). We report the heterologous expression, purification, determination of affinity binding constants and crystallization of the Desulfovibrio alaskensis G20 TupA. The tupA gene (locus tag Dde_0234) was cloned in the pET46 Enterokinase/Ligation-Independent Cloning (LIC) expression vector, and the construct was used to transform BL21 (DE3) cells. TupA expression and purification were optimized to a final yield of 10 mg of soluble pure protein per liter of culture medium. Native polyacrylamide gel electrophoresis was carried out showing that TupA binds both tungstate and molybdate ions and has no significant interaction with sulfate, phosphate or perchlorate. Quantitative analysis of metal binding by isothermal titration calorimetry was in agreement with these results, but in addition, shows that TupA has higher affinity to tungstate than molybdate. The protein crystallizes in the presence of 30% (w/v) polyethylene glycol 3350 using the hanging-drop vapor diffusion method. The crystals diffract X-rays beyond 1.4 Å resolution and belong to the P21 space group, with cell parameters a = 52.25 Å, b = 42.50 Å, c = 54.71 Å, β = 95.43°. A molecular replacement solution was found, and the structure is currently under refinement.

A relação sujeito-objeto se diferencia em cada uma das formas de transmissão de conhecimento,seja oral ou escrita, o que – para o estudo da Religião – denota uma unidade(homem religioso) expressa na diversidade (tradição oral e escrita). Tais aproximações econtrastes serão discutidos sob a ótica da Teologia com ênfase nas religiões afro-brasileiras em F. Rivas Neto considerando a Vertente Una do Sagrado, tempo mítico (circularidade),ancestralidade (primordial), senioridade, memória (inconsciente), linguagem simbólica(sentidos) e Comunidade. A Teologia aqui apresentada está em contato direto com a Ciência da Religião, Antropologia, Sociologia, História, Filosofia e essa característica multidisciplinar é chave importante para compreensão do objeto.

This paper evaluates the viability of installing photovoltaic (PV) systems in existing commercial buildings in Dublin. Data collected from previously installed photovoltaic systems at the Dublin Institute of Technology was analysed in order to determine the potential solar resource available in Ireland. A 1.1 kWp photovoltaic system installed in Dublin can produce over 900 kWh of electricity in a given year depending on the available solar resource for that year. A feasibility study was conducted in Dublin city centre in order to evaluate the technical, financial and environmental aspects of integrating a PV system into an existing building. The intention is that the results from this work will help in demonstrating the benefits and challenges associated with installing PV systems in existing commercial buildings in Ireland.

Background Treatment of central nervous system relapse in adult acute lymphoblastic leukemia is a challenge and outcome is poor. Liposomal cytarabine has a prolonged half-life and, given intrathecally, has produced high response rates in patients with central nervous system relapse of non-Hodgkin's lymphoma. The aim of this study was to evaluate the efficacy and tolerability of liposomal cytarabine in central nervous system relapse of acute lymphoblastic leukemia or Burkitt's lymphoma/leukemia.Design and Methods Liposomal cytarabine (50 mg) was given intrathecally together with systemic or intrathecal dexamethasone once every 2 weeks in a phase II European trial. The primary end-point, cytological response in the cerebrospinal fluid after one or two cycles, was evaluated at the time of next treatment.Results Nineteen heavily pretreated patients (median age, 53 years; range 24–76 years) were evaluable: 14 with acute lymphoblastic leukemia and 5 with Burkitt’s lymphoma/leukemia). Complete cytological remission as best response after two cycles of liposomal cytarabine was confirmed in 74% of the patients: 86% of those with acute lymphoblastic leukemia and 40% of those with Burkitt’s lymphoma/leukemia). Nine of the 14 patients who achieved complete remission relapsed after a median of 7 months. The median overall survival was 11 months. Adverse events were observed in 89% of the patients (57% of cycles). Grade III–IV events with potential correlation to liposomal cytarabine occurred in 32% of the patients. The most frequent adverse event was headache. One patient developed severe neurological complications with loss of vision and a conus syndrome.Conclusions Overall, liposomal cytarabine showed excellent antileukemic activity. Toxicity was acceptable but appeared to increase with the number of cycles. Future evaluation in prophylaxis is of interest

The deployment of energy monitoring systems is well established for industrial facilities and commercial buildings, however these systems are insufficient where large variations in activity level (production variation, one-off events) are common. In such cases, accurate analysis of energy usage requires the deployment of a flexible embedded sensor network that can capture data at the required level of accuracy and granularity and can associate the energy usage data with the context and activity that has caused it. This research proposes an approach and a set of hardware and software tools for the monitoring of energy usage in technical building services and the association of that data with real-time production information in advanced manufacturing facilities. The system developed incorporates an embedded controller with sensors to monitor the physical environment, an integrated energy analyser to monitor electricity consumption and a visualisation interface that associate events in the physical world with the actual energy consumption recorded. The creation of a detailed time-stamped energy profile for the process can then be used in the identification of energy saving opportunities. A case study from a pharmaceutical facility was used to validate the operation of the system. [ABSTRACT FROM AUTHOR]

La prevención, la intervención y la reparación en el sector del juego se convierten en basamentos sobre los que se vienen trazando los bocetos de nuevas normas, que en conjunto se prevé que ofrezcan un escenario de armonía en un ámbito cada día más complejo. Nuevos modelos de juegos y apuestas, el uso de medios tecnológicos y la proliferación de establecimientos en los que se desarrollan, han llevado a que desde enero de 2019 la Junta de Extremadura comenzase un proceso intenso de adaptación de las normas sobre el sector, tarea que se fundamenta en principios de juego responsable. La delimitación de qué se entiende por juego responsable, así como de la adopción de medidas de ordenación de las políticas de juego responsable darán protagonismo a las nuevas directrices normativas. Una labor que ha comenzado y requiere un arduo esfuerzo por parte de todos los agentes del sector en la que el papel de las Administraciones públicas se dibuja esencial. Antes, durante y después de la puesta en marcha de cada juego y de las distintas modalidades de apuestas se activarán las funciones de una Administración autonómica que orientará su actuación hacia objetivos de prevención y protección de los grupos vulnerables, en definitiva, de responsabilidad.

Manilkara zapota “chicozapote” is an autochthonous evergreen tree from the Southern regions of Mexico, Belize, and Guatemala. Currently, it is widely distributed and extensively grown in Mexico and Southeast Asia. Traditionally, different structures of the plant have been used for medical purposes; seeds have diuretic and purgative properties, aiding in digestive complications and eliminating bladder and kidney stones. Tree bark has antidiarrheal, antipyretic, antibiotic, and astringent properties. Fruits and leaves have been used to treat cold, cough, diarrhea, indigestion, fever, hemorrhages, wounds, and ulcers. Chicozapote fruit is yellow and brown, with an oval shape and rough peel, it is an excellent source of nutrients, such as sugars, proteins, amino acids, and minerals, and is rich in phytochemical components, such as flavonoids, phenolic acids, and tannins. These bioactive compounds exert several biological activities, i.e., as an antioxidant, antidiabetic, antimicrobial, anti-inflammatory, cytotoxic, and anti-arthritic agents, to name a few. These beneficial properties assist in preventing chronic and degenerative diseases, such as cancer, diabetes, neurological, infectious, and cardiovascular diseases. The use of chicozapote is still limited to its fresh form, and its non-edible structures produce a lot of waste. Therefore, an alternative valorizing and preserving strategy is to use the fruit as a raw source to design functional foods and pharmacological products. Here, the nutritional and phytochemical profiles and the current view regarding methodologies and conditions, for the extraction and characterization of its bioactive compounds, are described, and focus is placed on their multiple biological effects and specific functional mechanisms.

Polyps can be found throughout the intestine, but their presence in the small intestine is unusual. Hamartomatous polyps are seen in pathologies such as Peutz-Jeghers syndrome. We present a 17 year-old male with history of an incidental sigmoid polyp diagnosed as a neuroendocrine tumor, and later found with hamartomatous polyps mimicking a jejunal malignant tumor. To our knowledge, this is the first known case of a pediatric patient with this kind of presentation.

The main objective of this study was to evaluate the antioxidant capacity and possible toxicological potential of the infusions prepared from Ibervillea sonorae. For this, infusions were prepared from the root of I. sonorae, using the skin or the pulp. The antioxidant capacity of the infusions was evaluated through the ABTS and DPPH tests. While, the Artemia salina model, the MTT test using Vero and MCF-7 cells, and the Ames test were used to evaluate the possible toxicological potential. The results showed that I. sonorae peels were more lethal (60-80%) than pulp (

Hepatoblastomas exhibit the lowest mutational burden among pediatric tumors. We previously showed that epigenetic disruption is crucial for hepatoblastoma carcinogenesis. Our data revealed hypermethylation of nicotinamide N-methyltransferase, a highly expressed gene in adipocytes and hepatocytes. The expression pattern and the role of nicotinamide N-methyltransferase in pediatric liver tumors have not yet been explored, and this study aimed to evaluate the effect of nicotinamide N-methyltransferase hypermethylation in hepatoblastomas. We evaluated 45 hepatoblastomas and 26 non-tumoral liver samples. We examined in hepatoblastomas if the observed nicotinamide N-methyltransferase promoter hypermethylation could lead to dysregulation of expression by measuring mRNA and protein levels by real-time quantitative polymerase chain reaction, immunohistochemistry, and Western blot assays. The potential impact of nicotinamide N-methyltransferase changes was evaluated on the metabolic profile by high-resolution magic angle spinning nuclear magnetic resonance spectroscopy. Significant nicotinamide N-methyltransferase downregulation was revealed in hepatoblastomas, with two orders of magnitude lower nicotinamide N-methyltransferase expression in tumor samples and hepatoblastoma cell lines than in hepatocellular carcinoma cell lines. A specific TSS1500 CpG site (cg02094283) of nicotinamide N-methyltransferase was hypermethylated in tumors, with an inverse correlation between its methylation level and nicotinamide N-methyltransferase expression. A marked global reduction of the nicotinamide N-methyltransferase protein was validated in tumors, with strong correlation between gene and protein expression. Of note, higher nicotinamide N-methyltransferase expression was statistically associated with late hepatoblastoma diagnosis, a known clinical variable of worse prognosis. In addition, untargeted metabolomics analysis detected aberrant lipid metabolism in hepatoblastomas. Data presented here showed the first evidence that nicotinamide N-methyltransferase reduction occurs in hepatoblastomas, providing further support that the nicotinamide N-methyltransferase downregulation is a wide phenomenon in liver cancer. Furthermore, this study unraveled the role of DNA methylation in the regulation of nicotinamide N-methyltransferase expression in hepatoblastomas, in addition to evaluate the potential effect of nicotinamide N-methyltransferase reduction in the metabolism of these tumors. These preliminary findings also suggested that nicotinamide N-methyltransferase level may be a potential prognostic biomarker for hepatoblastoma.

Objetivo: Relatar a experiência de uma ação de educação permanente em saúde para a formação de agentes comunitários de saúde no cenário do COVID-19. Método: Trata-se de um relato de experiência vivenciado por uma acadêmica do curso de enfermagem que realizou uma ação de educação permanente em saúde para agentes comunitários de saúde por meio do uso de tecnologia virtual. Resultados: A educação permanente em saúde na modalidade virtual, durante a pandemia do COVID-19, constitui uma estratégia de qualificação de saberes e práticas no cenário da atenção básica em saúde para o enfrentamento do COVID-19 e promove a melhoria da qualidade do cuidado em saúde. Conclusão: A educação permanente em saúde por meio tecnologias virtuais mostrou-se como uma possibilidade de ensino-aprendizagem significativa e facilita a atuação dos agentes comunitários de saúde junto à comunidade.

This paper explores the application of spatial models to non-life insurance data focused on the multi-risk home insurance branch. In the pricing modelling and rating process, spatial information should be considered by actuaries and insurance managers because frequencies and claim sizes may vary by region and the premium should be different considering this rating variable. In addition, it is relevant to examine the spatial dependence due to the fact that the frequency of claims in neighbouring regions is often expected to be more closely related than those in regions far from each other. In this paper, a comparison between spatial models, such as spatial autoregressive models (SAR), the spatial error model (SEM), and the spatial Durbin model (SDM), and a non-spatial model has been developed. The data used for this analysis are for a home insurance portfolio located in Spain, from which we have selected peril of water coverage.

Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease resulting from variants in the WAS gene, characterized by a triad of immunodeficiency, eczema, and thrombocytopenia. Despite the fact that WAS is traditionally differentiated from immune thrombocytopenia (ITP) by small size of WAS platelets, in practice, microthrombocytopenia may occasionally not be present, and in certain cases, WAS patients exhibit some parallelism to ITP patients. We characterized one patient presenting with the classic form of the disease but increased mean platelet volume. Molecular studies revealed a novel hemizygous 1-bp deletion in WAS gene, c.802delC, leading to a frameshift and stop codon at amino acid 308 (p.Arg268Glyfs*40). Next-generation sequencing of a total of 70 additional genes known to harbor variants implicated in inherited platelet disorders did not identify additional defects. The pathogenesis of macrothrombocytopenia in this case is not known, but probably the coexistence of a still unidentified additional genetic variant might be involved.