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Abstract Background Therapeutic resistance is the main cause of death in metastatic colorectal cancer. To investigate genomic plasticity, most specifically of metastatic lesions, associated with response to first‐line systemic therapy, we collected longitudinal liver metastatic samples and characterized the copy number aberration (CNA) landscape and its effect on the transcriptome. Methods Liver metastatic biopsies were collected prior to treatment (pre, n = 97) and when clinical imaging demonstrated therapeutic resistance (post, n = 43). CNAs were inferred from whole exome sequencing and were correlated with both the status of the lesion and overall patient progression‐free survival (PFS). We used RNA sequencing data from the same sample set to validate aberrations as well as independent datasets to prioritize candidate genes. Results We identified a significantly increased frequency gain of a unique CN, in liver metastatic lesions after first‐line treatment, on chr18p11.32 harboring 10 genes, including TYMS, which has not been reported in primary tumors (GISTIC method and test of equal proportions, FDR‐adjusted p = 0.0023). CNA lesion profiles exhibiting different treatment responses were compared and we detected focal genomic divergences in post‐treatment resistant lesions but not in responder lesions (two‐tailed Fisher's Exact test, unadjusted p ≤ 0.005). The importance of examining metastatic lesions is highlighted by the fact that 15 out of 18 independently validated CNA regions found to be associated with PFS in this study were only identified in the metastatic lesions and not in the primary tumors. Conclusion This investigation of genomic‐phenotype associations in a large colorectal cancer liver metastases cohort identified novel molecular features associated with treatment response, supporting the clinical importance of collecting metastatic samples in a defined clinical setting.

Intitulado de “A desmilitarização da cultura”, o texto cuja tradução apresentamos é uma conferência realizada por Jean-Paul Sartre no Congresso Mundial para o Desarmamento Geral e a Paz, ocorrido em Moscou, na então URSS, em 1962. Nela, o filósofo francês discute o impacto da Guerra Fria sobre a cultura em geral, considerando que não apenas a tecnologia e a ciência tornaram-se militarizadas, mas também a literatura. Daí seu apelo por uma “desmilitarização da cultura”, denunciando a submissão da arte e da crítica especializada a uma lógica de guerra que consiste em tomar como estáticas as características contraditórias (em sentido dialético) de toda manifestação cultural possível: seu particularismo nacional e sua universalidade latente.

O presente artigo pretende revisitar as bases “fenomenológicas” da trajetória de Jean-Paul Sartre desde sua recepção das filosofias de Edmund Husserl e Martin Heidegger até o momento de composição da principal síntese filosófica de seu existencialismo, intitulada O Ser e o Nada (1943). Neste sentido, o artigo situa o estatuto das fenomenologias de Husserl e Heidegger para o pensamento sartriano, bem como a originalidade de O Ser e o Nada, para a qual concorre, ainda, uma leitura bastante particular da negatividade hegeliana.

Background To provide insight into bone turnover, quantitative measurements of bone remodeling are required. Radionuclide studies are widely used in clinical care, but have been rarely used in the exploration of the bone in preclinical studies. We describe a bone planar scintigraphy method for frequent assessment of bone activity in mice across the growing period. Since repeated venous radiotracer injections are hardly feasible in mice, we investigated the subcutaneous route. Methods Repeated 99mTc-hydroxymethylene diphosphonate (HMDP) tracer bone planar scintigraphy studies of the knee region and µCT to measure femur growth rate were performed in eight mice between week 6 and week 27 of life, i.e., during their growth period. Three independent investigators assessed the regions of interest (ROI). An index was calculated based on the counts in knees ROI (normalized by pixels and seconds), corrected for the activity administered, the decay between administration and imaging, and individual weights. Results A total of 93 scintigraphy studies and 85 µCT were performed. Repeated subcutaneous tracer injections were well tolerated and allowed for adequate radionuclide studies. Mean scintigraphic indexes in the knees ROI decreased from 87.4 ± 2.6 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 6 to 15.0 ± 3.3 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 27. The time constant of the fitted exponential decay was equal to 23.5 days. As control mean femur length assessed by µCT increased from 12.2 ± 0.8 mm at week 6 to 15.8 ± 0.2 mm at week 22. The time constant of the fitted Gompertz law was equal to 26.7 days. A correlation index of −0.97 was found between femur growth and decrease of bone tracer activity count between week 6 and 24. Conclusion This methodological study demonstrates the potential of repeated bone planar scintigraphy in growing mice, with subcutaneous route for tracer administration, for quantitative assessment of bone remodeling.

Partindo da disjuntiva neoliberal entre a vida e o lucro (ou a vida ou o lucro), o propósito deste artigo é o de discutir, no contexto da crise provocada pelo coronavírus, o conceito central de biopolítica em termos de uma gestão da morte ou, mais exatamente, de uma necropolítica.

Este artigo pretende revisitar o já célebre debate entre Michel Foucault e Jacques Derrida a propósito de História da loucura (1961), tese doutoral de Foucault. Neste sentido, queremos explorar a interpretação de História da loucura por Derrida destacando os principais pontos da controvertida polêmica desencadeada a respeito dos temas da razão, da loucura e da história na primeira das obras arqueológicas de Foucault. The purpose of this article is to revisit the famous debate between Michel Foucault and Jacques Derrida concerning Madness and Civilization (1961), Foucault’s doctoral thesis. In this sense, we would like to explore Derrida’s interpretation of Madness and Civilization to outline the main points of the polemical triggered about the themes of reason, madness and history in Foucault’s first archaeological work.

O presente trabalho examina as relações entre as noções de poder soberano, biopoder e governamentalidade liberal no pensamento de Michel Foucault a fim de explorar alguns de seus nexos e de seus possíveis usos em nossa atualidade. Nesse sentido, ao passo que a primeira e a segunda parte deste artigo procuram mapear a temática da soberania e do biopoder no pensamento do próprio Foucault, a última parte dedica-se a assinalar, pontualmente, as interlocuções que Giorgio Agamben, Roberto Esposito e Achille Mbembe estabelecem com o tema em foco.

O presente trabalho tem por objetivo examinar a leitura do estoicismo por Michel Foucault, em particular o tratamento dispensado à filosofia de Epicteto, a fim de explorar sua abordagem temática da noção de “cuidado de si” na Antiguidade greco-romana. Neste sentido, o artigo pretende analisar o que Foucault entende por “cuidado de si” no contexto geral de sua genealogia ética e o deslocamento da questão do poder de um paradigma de subjugação para um outro, relacionado à auto constituição de si. Deste modo, o lugar privilegiado destinado à filosofia estóica nos trabalhos tardios de Foucault deve ser compreendido como um esforço para relacionar o sujeito da ação com o princípio da imanência ética que fundamenta a crítica foucaultiana ao sujeito.

O artigo pretende explorar as relações cambiantes entre loucura e razão, linguagem e sentido, saber e poder, psicanálise e psiquiatria em História da loucura (1961) para delinear os principais lugares destinados a Sigmund Freud em algumas das obras arqueológicas e genealógicas de Michel Foucault.

O artigo pretende explorar as relações cambiantes entre loucura e razão, linguagem e sentido, saber e poder, psicanálise e psiquiatria em História da loucura (1961) para delinear os principais lugares destinados a Sigmund Freud em algumas das obras arqueológicas e genealógicas de Michel Foucault.

Mobile devices, such as tablets and smartphones, are increasingly present in the everyday life of young people. Despite such insertion, the use of those devices in scenarios such as m-learning is still a missed opportunity. In a previous work we verified that an editor that aggregates various kinds of media can help students in their studies. With that motivation in mind, we realized the Multimodal Editor – a useful tool to leverage the multimedia authorship. In this paper we describe our trajectory toward the Editor – requirements gathering, implementation, challenges, usage scenario and evaluation.

A partir da correlação, postulada pelo pensamento de Michel Foucault, entre o exercício do poder e a manifestação da verdade, o presente artigo pretende retraçar as exigências políticas de sua filosofia, relacionando-as com a figura de um tipo intelectual que tem por função não mais a defesa da universalidade, mas sim sua transgressão política e teórica - quer dizer: "política" porque "teórica".From the correlation, postulated by the thought of Michel Foucault, between the exercise of the power and manifestation of the truth, this paper aims to retrace the political demands of his philosophy, linking them to the figure of an intellectual type who has no more basis for the defense of universality, but its political and theoretical transgression - it means: "political" because "theoretical".

Il s’agit, dans cet article, de mettre en rapport quatre textes ou passages fondamentaux de l’oeuvre foucaultienne; passages qui, dans l’ensembe et compte tenu de l’analyse de la littérature ou des arts figuratifs chez Foucault, constituent trois étapes de son parcours: 1) les pages renvoyant à l’analyse du tableau Las meninas, de Velázquez, dans Les mots et les choses (1966); 2) une conférence s’intitulant La peinture de Manet qu’il a donnée en Tunisie (1971); 3) un texte dont le titre est La peinture photogénique, qu’il a écrit pour le catalogue d’une exposition consacrée au peintre Fromanger (1975); 4) son texte célèbre, Qu’est-ce que les Lumières? (1984), où le philosophe aborde la question de l’Aufklärung chez Kant en déplaçant le centre de la réflexion sur les Lumières du plan relatif à une “école” ou à un “mouvement philosophique” au plan concernant essentiellement la question d’un “diagnostic du présent”.

The present article describes three difficult cases of recurrent bleeding from obscure causes, followed by a review of the pitfalls and pharmacological management of obscure gastrointestinal bleeding. All three patients underwent multiple investigations. An intervening complicating diagnosis or antiplatelet drugs may have compounded long-term bleeding in two of the cases. A bleeding angiodysplasia was confirmed in one case but was aggravated by the need for anticoagulation. After multiple transfusions and several attempts at endoscopic management in some cases, long-acting octreotide was associated with decreased transfusion requirements and increased hemoglobin levels in all three cases, although other factors may have contributed in some. In the third case, however, the addition of low-dose thalidomide stopped bleeding for a period of at least 23 months.

A partir do exame da conduta interrogativa e da descrição da ausência em L’être et le néant, obra capital de Jean-Paul Sartre, pretende-se lançar luzes sobre a questão do Nada enquanto manifestação do não-ser na realidade humana. Palavras-chave: consciência, fenômeno, Nada, não-ser, ontologia-fenomenológica.

Under the light of Being and Nothingness's theoretical body - Sartre's master piece -, it is intended to discuss the essential source of human reality as "nihilation" and ontological lack, as well as manifestations and consequences from this primordial human passion to be transformed to coagulated transcendence, to be transformed in Being In-itself-For-itself: to be consciousness and, at the same time, to be a complete and finished Being, with infinite density and without fissures.

BackgroundThe RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked dominant genetic disorder causing mental retardation, skeletal growth delays, with craniofacial and digital abnormalities typically associated with this syndrome. Craniofacial and dental anomalies encountered in this rare disease have been poorly characterized.Methodology/principal findingsWe examined, using X-Ray microtomographic analysis, the variable craniofacial dysmorphism and dental anomalies present in Rsk2 knockout mice, a model of Coffin-Lowry syndrome, as well as in triple Rsk1,2,3 knockout mutants. We report Rsk mutation produces surpernumerary teeth midline/mesial to the first molar. This highly penetrant phenotype recapitulates more ancestral tooth structures lost with evolution. Most likely this leads to a reduction of the maxillary diastema. Abnormalities of molar shape were generally restricted to the mesial part of both upper and lower first molars (M1). Expression analysis of the four Rsk genes (Rsk1, 2, 3 and 4) was performed at various stages of odontogenesis in wild-type (WT) mice. Rsk2 is expressed in the mesenchymal, neural crest-derived compartment, correlating with proliferative areas of the developing teeth. This is consistent with RSK2 functioning in cell cycle control and growth regulation, functions potentially responsible for severe dental phenotypes. To uncover molecular pathways involved in the etiology of these defects, we performed a comparative transcriptomic (DNA microarray) analysis of mandibular wild-type versus Rsk2-/Y molars. We further demonstrated a misregulation of several critical genes, using a Rsk2 shRNA knock-down strategy in molar tooth germs cultured in vitro.ConclusionsThis study reveals RSK2 regulates craniofacial development including tooth development and patterning via novel transcriptional targets.

The desmoplastic small round cell tumor (DSRCT) is an uncommon and highly aggressive cancer. The role of 18F-FDG PET in management of DSRCT is little reported. We report a case of metastasized abdominal DSRCT detected in a 43-year old patient whose diagnostic and therapeutic approaches were influenced by 18F-FDG PET-CT. The patient is still alive ten years after diagnosis. 18F-FDG PET-CT seems to be a useful method for assessing therapeutic efficiency and detecting early recurrences even in rare malignancies such as DSRCT.

This paper exploits the idea that each individual brain region has a specific connection profile to create parcellations of the cortical mantle using MR diffusion imaging. The parcellation is performed in two steps. First, the cortical mantle is split at a macroscopic level into 36 large gyri using a sulcus recognition system. Then, for each voxel of the cortex, a connection profile is computed using a probabilistic tractography framework. The tractography is performed from q-ball fields using regularized particle trajectories. Fiber ODF are inferred from the q-balls using a sharpening process focusing the weight around the q-ball local maxima. A sophisticated mask of propagation computed from a T1-weighted image perfectly aligned with the diffusion data prevents the particles from crossing the cortical folds. During propagation, the particles father child particles in order to improve the sampling of the long fascicles. For each voxel, intersection of the particle trajectories with the gyri lead to a connectivity profile made up of only 36 connection strengths. These profiles are clustered on a gyrus by gyrus basis using a K-means approach including spatial regularization. The reproducibility of the results is studied for three subjects using spatial normalization.

The use of iterative algorithms in tomographic reconstruction always leads to a frequency adapted rate of convergence in that low frequencies are accurately reconstructed after a few iterations, while high frequencies sometimes require many more computations. In this paper, we propose to build frequency adapted (FA) algorithms based on a condition of incomplete backprojection and propose an FA simultaneous algebraic reconstruction technique (FA-SART) algorithm as an example. The results obtained with the FA-SART algorithm demonstrate a very fast convergence on a highly detailed phantom when compared to the original SART algorithm. Though the use of such an FA algorithm may seem difficult, we specify in which case it is relevant and propose several ways to improve the reconstruction process with FA algorithms.