Current Applications and Challenges of Next-Generation Sequencing in Plasma Circulating Tumour DNA of Ovarian Cancer.

Circulating tumour DNA (ctDNA) facilitates longitudinal study of the tumour genome, which, unlike tumour tissue biopsies, globally reflects intratumor and intermetastatis heterogeneity. Despite its costs, next-generation sequencing (NGS) has revolutionised the study of ctDNA, ensuring a more comprehensive and multimodal approach, increasing data collection, and introducing new variables that can be correlated with clinical outcomes. Current NGS strategies can comprise a tumour-informed set of genes or the entire genome and detect a tumour fraction as low as 10-5. Despite some conflicting studies, there is evidence that ctDNA levels can predict the worse outcomes of ovarian cancer (OC) in both early and advanced disease. Changes in those levels can also be informative regarding treatment efficacy and tumour recurrence, capable of outperforming CA-125, currently the only universally utilised plasma biomarker in high-grade serous OC (HGSOC). Qualitative evaluation of sequencing shows that increasing copy number alterations and gene variants during treatment may correlate with a worse prognosis in HGSOC. However, following tumour clonality and emerging variants during treatment poses a more unique opportunity to define treatment response, select patients based on their emerging resistance mechanisms, like BRCA secondary mutations, and discover potential targetable variants. Sequencing of tumour biopsies and ctDNA is not always concordant, likely as a result of clonal heterogeneity, which is better captured in the plasma samples than it is in a large number of biopsies. These incoherences may reflect tumour clonality and reveal the acquired alterations that cause treatment resistance. Cell-free DNA methylation profiles can be used to distinguish OC from healthy individuals, and NGS methylation panels have been shown to have excellent diagnostic capabilities. Also, methylation signatures showed promise in explaining treatment responses, including BRCA dysfunction. ctDNA is evolving as a promising new biomarker to track tumour evolution and clonality through the treatment of early and advanced ovarian cancer, with potential applicability in prognostic prediction and treatment selection. While its role in HGSOC paves the way to clinical applicability, its potential interest in other histological subtypes of OC remains unknown.

The accuracy of magnetic resonance imaging in predicting the size of pure ductal carcinoma in situ: a systematic review and meta-analysis.

Ductal carcinoma in situ (DCIS) is a putative precursor of invasive breast cancer and MRI is considered the most sensitive imaging technique for its detection. This study aims to evaluate the accuracy of MRI measuring the pure DCIS size, against pathology, to better understand the role of MRI in the management of this intraductal neoplasm.Potentially eligible studies in MEDLINE, Embase and Google Scholar, up to January 2021 were considered, and a systematic review and meta-analysis according to the published protocol (Prospero-CRD42021232228) was performed. Outcomes of mean differences and accuracy rates were analysed using IBM® SPSS® v26 and random-effect models in platform R v3.3.Twenty-two cross-sectional studies were selected and 15 proceeded to meta-analysis. MRI accurately predicted 55% of the tumours' sizes and, according to Bland-Altman plots, concordance between MRI and pathology was greater for smaller tumours. In the meta-analysis, difference of the means between MRI and pathology was 3.85 mm (CI 95% [-0.92;8.60]) with considerable heterogeneity (I2 = 96.7%). Subgroup analysis showed similar results for sizes between different MRI fields, temporal resolution, slice thickness and acquisition times, but lower heterogeneity in studies using 3-T MRI (I2 = 57.2%). Results were concordant with low risk of bias studies (2.46, CI 95% [0.57-4.36]), without heterogeneity (I2 = 0%).Therefore, MRI is shown to be an accurate method in pure DCIS size assessment. Once the best MRI protocol is established, evaluation of the impact of pure DCIS size in predicting treatment outcomes will contribute to clarifying current issues related to intraductal breast carcinoma.

The Latin stranger-science, or l'anthropologie among the Lusitanians.

This essay traces the connected histories of Portuguese and French anthropology in the late nineteenth century. By looking at a Portuguese scientific institution, the Carlos Ribeiro Society, it considers how French race science, known as anthropologie, was adopted and adapted across the European Latin world as a type of "stranger-science." That is: as an authoritative outsider scientific formation, installed into national terrain in accordance with insider strategies for turning foreign elements into native forms of scientific sovereignty and modernity. French anthropology's international diffusion becomes meaningful in the light of the Portuguese incorporating what was foreign and modern as a means to generate vitality, and authority endogenously in their own national context. Hence, addressing the circulation of stranger-sciences can pave the way for an original conceptualizing of the transnational life of race science across and even beyond the Latin world.

Impact of COVID-19 Pandemic on In-Hospital Mortality in Patients Without SARS-CoV-2 Infection in an Internal Medicine Ward of a Tertiary Care Hospital in Portugal.

INTRODUCTION: Despite the emergence of a new worldwide cause of death related to COVID-19, several studies have hypothesized that the international mortality rate attributed to non-COVID-19 causes was significantly higher during the COVID pandemic, questioning whether this excess in mortality is related only to COVID-19 or to the difficulties that the healthcare systems faced during the pandemic. Therefore, understanding the impact of the COVID-19 pandemic on the prognosis of patients without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major unmet need as this was overshadowed by the overwhelming number of patients with SARS-CoV-2. METHODS: This is a retrospective, cross-sectional, observational study in the internal medicine non-COVID-19 wards of a tertiary care hospital in Portugal. A total of 2021 patients without SARS-CoV-2 infection admitted between March and May of 2019 and 2020 were included. For each patient, we collected information regarding demographic characteristics, emergency department admission information, hospitalization information, date of discharge or death, health comorbidities, and current medication. RESULTS: Data from 1013 patients in 2019 and 1008 patients in 2020 was analyzed. The patients' demographic characteristics, health comorbidities, and current medications were distributed in similar patterns in the two studied periods. There was a statistically significant difference in the in-hospital mortality in patients without SARS-CoV-2 infection between 2019 and 2020 (12% vs 17%, p-value < 0.001) and in admission severity in hospitalized patients without SARS-CoV-2 infection between 2019 and 2020 (0.9 vs 0.6, p-value < 0.001). CONCLUSION: Our work showed a statistically significant increase in in-hospital mortality during the COVID-19 pandemic in patients without SARS-CoV-2 infection, which was not apparently explained by differences in the characteristics of hospitalized patients. As this is one of the first works describing the silent impact of the COVID-19 pandemic in Portugal, we believe it holds an important value in the provision of bases for building up future health policies in case of new COVID-19 outbreaks or other medical emergencies.

Oligosecretory multiple myeloma: a devastating presentation of a difficult diagnosis.

A 57-year-old man with lumbar pain and fever was diagnosed with spondylodiscitis. Afterward, he acquired full paraplegia. Image studies showed a mass extending from D9 to the vertebral canal, plus numerous adjacent osteolytic lesions. Serum immunoelectrophoresis was normal, bone marrow had 0.5% of monoclonal plasmocytes, but D9's biopsy found a plasmacytoma. Despite bone marrow aspiration results, skeleton osteolytic lesions made multiple myeloma (MM) a more plausible diagnosis, later confirmed by the biopsy. The absence of classical MM findings, alongside a medullary compression syndrome, suggested an oligosecretory MM, which was proved by an altered FLC essay. This delayed diagnosis, with multiple diagnostic misguiding leads, also presents rare IgA and lambda chains production and normal levels of uninvolved immunoglobulins. Oligosecretory MM can lead to an inaccurate and delayed diagnosis, with devastating consequences to patient's morbidity and mortality. Therefore, FLC essay is essential in early assessment of potential MM patients.

Epithelial-mesenchymal interconversions in ovarian cancer: The levels and functions of E-cadherin in intraabdominal dissemination.

The metastatic process of ovarian cancer (OC) is almost exclusively defined by direct shedding of tumor cells into the abdominal cavity, followed by clustering into multicellular aggregates and posterior peritoneal anchorage. This process relies on dynamic intercellular interactions which are modified by epithelial- mesenchymal interconversions and, therefore, E-cadherin expression variability. Although widely accepted as a tumor suppressor in many types of cancer, E-cadherin is currently known to have a dynamic expression and a much more complex role in OC. First, high E-cadherin expression is considered a sign of metaplasia in the normal ovarian epithelium, due to its association with epithelial growth factor receptor (EGFR) mediated cell proliferation. Subsequently, it is the decreased expression of E-cadherin that allows the acquisition of a more invasive phenotype, leading to the spread of primary tumor cells into the peritoneal fluid. This downregulation seems to depend on complex regulatory mechanisms, from molecular proteolysis to microenvironment interference and epigenetic regulation. E-cadherin cleavage and its resulting fragments appear to be essential to the process of dissemination and even to the formation of multicellular aggregates. Paradoxically, the maintenance of some E-cadherin expression seems to promote intercellular adhesion, resistance, and survival while decreasing cancer response to chemotherapy. Multiple studies have shown that reversing epithelial-mesenchymal transaction (EMT) and increasing E-cadherin expression prevents OC intraperitoneal dissemination, but findings that simultaneously correlate E-cadherin downregulation to higher chemotherapy sensitivity should not be ignored. Nevertheless, EMT and E-cadherin seem to have a potential interest as therapeutic targets in novel approaches to OC treatment.

Tortuosidade e conectividade da rede trabecular do rádio distal a partir de imagens microtomográficas / Trabecular network tortuosity and connectivity of distal radius from microtomographic images

A osteoporose é uma doença que causa perda de massa óssea e deterioração da estrutura trabecular. A rede formada pelo osso trabecular é muito importante para estabelecer a competência mecânica do esqueleto. Estudos mostram que a microarquitetura trabecular pode elevar a predição do risco de fratura para cerca de 90 por cento , por isso a sua investigação é de grande interesse da comunidade científica. Vários parâmetros estão relacionados à competência mecânica da estrutura óssea, entretanto, a tortuosidade trabecular ainda não foi seriamente levada em consideração e sua contribuição é desconhecida. Neste trabalho, o enfoque está direcionado à estimativa da tortuosidade trabecular e sua correlação com a conectividade, através da característica de Euler-Poincaré, para amostras do osso rádio distal in  vitro, a partir de imagens de microtomografia computadorizada. Um método para estimar a tortuosidade do volume trabecular é apresentado e a tortuosidade é computada para os dois sentidos das três direções do volume. Os resultados apresentam valores distintos da tortuosidade dependendo da qualidade da rede trabecular e uma correlação positiva (r  =   0,64) com a característica de Euler-Poincaré; além disso, observa-se que a tortuosidade busca alinhar-se nas direções de maiores tensões e compressões imprimidas à rede trabecular. Tais resultados evidenciam a importância da tortuosidade como parâmetro estrutural da rede trabecular.

Osteoporosis is disease causing bone mass loss and deterioration of the trabecular structure. The trabecular network is very important to establish the mechanical competence of the skeleton. It is known that the trabecular microarchitecture can improve the fracture risk prediction up to 90 percent , for this reason the trabecular bone investigation has become of great interest for the scientific community. Several parameters provide structural details of the bone mechanical competence, however, the trabecular network tortuosity has not been seriously taken into account yet and its contribution is unknown. This paper directs attention to the trabecular tortuosity estimation and its correlation to the connectivity, through Euler-Poincaré characteristic, from in  vitro distal radius bone samples by micro-computed tomographic images. A method to estimate the trabecular bone tortuosity is presented and its value is computed for both directions of the three volume axis. The results indicate that the trabecular tortuosity depends on the trabecular network quality and a positive correlation (r  = 0.64) with the Euler-Poincaré characteristic. Inasmuch, it has been observed that the tortuosity tends to get aligned in the direction of main stress imposed on trabecular bone network. These results support the tortuosity as an important structural parameter.

Stories, skulls, and colonial collections.

The essay explores the hypothesis of colonial collecting processes involving the active addition of the colonial context and historical past to museum objects through the production of short stories. It examines the emergent historicity of collections through a focus on the "histories" that museum workers and colonial agents have been attaching to scientific collections of human skulls. Drawing on the notions of collection trajectory and historiographical work, it offers an alternative perspective from which to approach the creation of singular histories and individual archives for objects in collections.

[Seeds against smallpox: Joaquim Vás and the scientific translation of bananeira brava seeds in Goa, India (1894-1930)]. / Sementes contra a varíola: Joaquim Vás e a tradução científica das pevides de bananeira brava em Goa, lndia (1894-1930).

In 1914, in the former Portuguese colony of Goa, India, the physician António Joaquim Vás announced the discovery of a wonderful treatment for smallpox, entailing clinical application of seeds from the bananeira brava (Heliconia biabi Sw.m.), a plant remedy allegedly derived from Indian medical practices. The present article explores the circumstances surrounding the successes and failures of this discovery. The concept of scientific translation is used to interpret the transformation of bananeira brava seeds into an early twentieth-century remedy for smallpox. This transfer from indigenous use to scientific therapeutic constitutes the creation of a quasi-medicine, that is, a case of 'medium translation'. Although these seeds occupy a problematic place within the program of scientific translation, they enjoyed active circulation within science and remained a part of medical practices for combating smallpox.

Sementes contra a varíola: Joaquim Vás e a tradução científica das pevides de bananeira brava em Goa, índia (1894-1930) / Seeds against smallpox: Joaquim Vás and the scientific translation of bananeira brava seeds in Goa, India (1894-1930)

Em 1914, em Goa, antiga colônia portuguesa na índia, o médico António Joaquim Vás anunciou a descoberta de um fabuloso tratamento contra a varíola: a aplicação clínica das pevides, ou sementes, de bananeira brava, medicamento de origem vegetal extraído das práticas médicas indianas. Este artigo investiga as circunstâncias do sucesso e insucesso dessa descoberta. A constituição das pevides de bananeira brava como medicamento contra a varíola, no início do século XX, é interpretada com base no conceito de tradução científica. Argumenta-se que a tradução das pevides - de atividade indígena a terapêutica científica - constitui um caso de criação de quasi-medicamentos, uma tradução média. Embora habitando um lugar problemático no programa de tradução científica, as pevides circularam ativamente no interior da própria ciência, persistindo contra a varíola nas práticas médicas.

Aspectos ergonómicos de la actividad músculo esquelética localizada y repetitiva / Ergonomic aspects of muscle skeletal activity circumscribed and repetitive

En el presente trabajo se efectúa un análisis resumido de algunos elementos teóricos y prácticos a ser tenido en cuenta en la configuración de puestos de trabajo y el diseño de productos industriales, donde se observe la actividad músculo esquelética localizada y repetitiva

Aspectos ergonómicos de la actividad músculo esquelética localizada y repetitiva / Ergonomic aspects of muscle skeletal activity circumscribed and repetitive

En el presente trabajo se efectúa un análisis resumido de algunos elementos teóricos y prácticos a ser tenido en cuenta en la configuración de puestos de trabajo y el diseño de productos industriales, donde se observe la actividad músculo esquelética localizada y repetitiva (AU)

Consideraciones ergonómicas sobre el trabajo muscular estático / Ergonomic considerations concerning the static muscular work

Desde el punto de vista ergonómico se pretende dar algunas opiniones con respecto al trabajo muscular estático. Las mismas se basan en marcos teóricos y conocimientos empíricos de distintas disciplinas y tienen la finalidad de poder dar soluciones concretas en la configuración de las actividades laborales contemplando el incremento de la calidad de vida y una mayor productividad

Consideraciones ergonómicas sobre el trabajo muscular estático / Ergonomic considerations concerning the static muscular work

Desde el punto de vista ergonómico se pretende dar algunas opiniones con respecto al trabajo muscular estático. Las mismas se basan en marcos teóricos y conocimientos empíricos de distintas disciplinas y tienen la finalidad de poder dar soluciones concretas en la configuración de las actividades laborales contemplando el incremento de la calidad de vida y una mayor productividad (AU)

Algunos criterios ergonómicos sobre la fatiga y el descanso / Some ergonomic criteria about fatigue and rest

La asignación de la duración y la distribución de las pausas están estrechamente ligada al incremento de la calidad de vida y al de una mayor productividad. Si bien es cierto que tales asignaciones dadas principalmente en la industria pro medio de la experiencia adolecen de la falta de una base científica consistente, no por ello dejan de ser una parte importante del estudio egonómico. Desde el punto de vista del analista de trabajo, el hecho de otorgar tiempos de descanso sin un criterio que considere conocimientos acerca de la carga laboral y el esfuerzo necesario para la ejecución de una tarea, hace por lo general a una deficiente configuración del sistema productivo

Algunos criterios ergonómicos sobre la fatiga y el descanso / Some ergonomic criteria about fatigue and rest

La asignación de la duración y la distribución de las pausas están estrechamente ligada al incremento de la calidad de vida y al de una mayor productividad. Si bien es cierto que tales asignaciones dadas principalmente en la industria pro medio de la experiencia adolecen de la falta de una base científica consistente, no por ello dejan de ser una parte importante del estudio egonómico. Desde el punto de vista del analista de trabajo, el hecho de otorgar tiempos de descanso sin un criterio que considere conocimientos acerca de la carga laboral y el esfuerzo necesario para la ejecución de una tarea, hace por lo general a una deficiente configuración del sistema productivo (AU)

Ergonomía y productividad / Ergonomy and productivity

Actualmente en latinoamérica se replantean modelos de evaluación que permitan ponderar el desarrollo socioeconómico basado en el bienestar del hombre y la productividad, para poder competir con éxito en los mercados. A modo de ejemplo, en las Naciones Unidas se están realizando evaluaciones cualitativas de más de 150 países por medio de un Indice de Desarrollo Humano (1991) que considera los siguientes elementos: esperanza de vida, nivel de conocimiento e ingreso per cápita.

Ergonomía y productividad / Ergonomy and productivity

Actualmente en latinoamérica se replantean modelos de evaluación que permitan ponderar el desarrollo socioeconómico basado en el bienestar del hombre y la productividad, para poder competir con éxito en los mercados. A modo de ejemplo, en las Naciones Unidas se están realizando evaluaciones cualitativas de más de 150 países por medio de un Indice de Desarrollo Humano (1991) que considera los siguientes elementos: esperanza de vida, nivel de conocimiento e ingreso per cápita. (AU)