Personalized Pancreatic Tumor Growth Prediction via Group Learning

Tumor growth prediction, a highly challenging task, has long been viewed as a mathematical modeling problem, where the tumor growth pattern is personalized based on imaging and clinical data of a target patient. Though mathematical models yield promising results, their prediction accuracy may be limited by the absence of population trend data and personalized clinical characteristics. In this paper, we propose a statistical group learning approach to predict the tumor growth pattern that incorporates both the population trend and personalized data, in order to discover high-level features from multimodal imaging data. A deep convolutional neural network approach is developed to model the voxel-wise spatio-temporal tumor progression. The deep features are combined with the time intervals and the clinical factors to feed a process of feature selection. Our predictive model is pretrained on a group data set and personalized on the target patient data to estimate the future spatio-temporal progression of the patient's tumor. Multimodal imaging data at multiple time points are used in the learning, personalization and inference stages. Our method achieves a Dice coefficient of 86.8% +- 3.6% and RVD of 7.9% +- 5.4% on a pancreatic tumor data set, outperforming the DSC of 84.4% +- 4.0% and RVD 13.9% +- 9.8% obtained by a previous state-of-the-art model-based method

SETDB1 prevents TET2-dependent activation of IAP retroelements in naïve embryonic stem cells

Background Endogenous retroviruses (ERVs), which are responsible for 10% of spontaneous mouse mutations, are kept under control via several epigenetic mechanisms. The H3K9 histone methyltransferase SETDB1 is essential for ERV repression in embryonic stem cells (ESCs), with DNA methylation also playing an important role. It has been suggested that SETDB1 protects ERVs from TET-dependent DNA demethylation, but the relevance of this mechanism for ERV expression remains unclear. Moreover, previous studies have been performed in primed ESCs, which are not epigenetically or transcriptionally representative of preimplantation embryos. Results We use naïve ESCs to investigate the role of SETDB1 in ERV regulation and its relationship with TET-mediated DNA demethylation. Naïve ESCs show an increased dependency on SETDB1 for ERV silencing when compared to primed ESCs, including at the highly mutagenic intracisternal A particles (IAPs). We find that in the absence of SETDB1, TET2 activates IAP elements in a catalytic-dependent manner. Surprisingly, TET2 does not drive changes in DNA methylation levels at IAPs, suggesting that it regulates these retrotransposons indirectly. Instead, SETDB1 depletion leads to a TET2-dependent loss of H4R3me2s, which is indispensable for IAP silencing during epigenetic reprogramming. Conclusions Our results demonstrate a novel and unexpected role for SETDB1 in protecting IAPs from TET2-dependent histone arginine demethylation

PROTOCOLO DE DESINFECÇÃO DE MOLDAGENS

Após  realizar  o  procedimento  de  confecção  de  moldagem  de prótese  é  necessário  que  haja  sua  desinfecção  com  uma  técnica  menos agressiva  que  a  esterilização.  Segue  uma  ordem  de  lavagem  com desencrostante, enxágue e desinfecção posterior. A necessidade de tal técnica tem  finalidade  de  prevenir  a  contaminação  cruzada,  causada  pela  saliva  e sangue  encontrados  na  superfície  do  molde,  que  é  considerada  de  grande potencial  de  contaminação.  Tal  procedimento  pode  ser  realizado  com  uma variedade  de  desinfectantes,  cada  um  com  uma  indicação  própria.  O  objetivo dessa mesa demonstrativa é levar ao conhecimento da comunidade acadêmica as  técnicas  de  desinfecção  de  moldagens  em  prótes

Multiple inflammatory markers and 15-year incident ADL disability in admixed older adults: The Bambui-Epigen Study

BACKGROUND: The ability of inflammatory markers to predict disability in later life has received growing attention. However, the current evidence came predominantly from Caucasians and the role of genomic ancestry has not been investigated. OBJECTIVE: We investigated the prognostic value of multiple citokynes and chemokines for incident disability in admixed older Brazilians and whether genomic African and Native American ancestry affects the association. DESIGN: Population-based longitudinal study. SETTING: The Bambui-Epigen (Brazil) Cohort Study of Aging. SUBJECTS: 1171 males and females aged ≥60 years over 15-year of follow-up. METHODS: Outcome examined was incident activity of daily living (ADL) disability assessed annually (10,039 measures were performed). Serum levels of citokynes (IL6, IL12, TNF, IL10, and IL1β) and chemokines (CCL2, CCL5, CXCL8, CXCL9 and CXCL10) were measured at baseline. We used 370,539 Single Nucleotide Polymorphisms (SNPs) to estimate each individual genomic ancestry proportions. Potential confounding variables included a wide range of socio-demographic variables and health indicators. Statistical analyses were based on competing risk framework. RESULTS: The incidence rate of disability was 57.9 per 1000 person-years. IL6 level at the highest quartile showed an independent association with ADL disability (SRH = 1.32; 95% CI: 1.03, 1.70). Other inflammatory markers showed no statistically significant associations with the outcome. Neither genomic African nor Native American ancestry had an effect modifier on the associations (P for interaction >0.05 for all). CONCLUSION: Among multi-inflammatory markers, only IL6 had the potential to identify people at increased risk of ADL disability, independently of ethno-racial background

CONSULTA DE ENFERMAGEM NO AMBULATÓRIO DE HIV/AIDS: A PERCEPÇÃO DOS USUÁRIOS

O estudo busca analisar como a consulta de enfermagem é percebida pelos usuários de um ambulatório especializado em Vírus da Imunodeficiência Humana/Síndrome da Imunodeficiência Adquirida (HIV/AIDS) no município de Fortaleza-CE. Trata-se de um estudo exploratório e descritivo, com abordagem qualitativa. Os dados foram coletados através de entrevista semiestruturada com quinze usuários da referida instituição e analisados com o suporte da análise de conteúdo. A consulta de enfermagem foi relatada pelos usuários como um momento de aprendizado, centrado no fornecimento de informações. A confiança e o apoio emocional estabelecido pelo profissional atuam como um suporte frente aos conflitos vivenciados pelo paciente, possibilitando a construção de um novo olhar frente à doença. Acreditamos que a realização da consulta de enfermagem em uma perspectiva dialogal poderá proporcionar aos sujeitos a ressignificação dos conflitos que permeiam o seu adoecimento

Skeletal Adaptation to Intramedullary Pressure-Induced Interstitial Fluid Flow Is Enhanced in Mice Subjected to Targeted Osteocyte Ablation

Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading. Collectively, these studies indicate that structural adaptation to ImP-driven IFF can proceed unimpeded following a significant depletion in osteocytes, consistent with the potential existence of a non-osteocytic bone cell population that senses ImP-driven IFF independently and potentially parallel to osteocytic sensation of poroelasticity-derived IFF