Classification and biomarker selection in lower-grade glioma using robust sparse logistic regression applied to RNA-seq data

Funding Information: This work was supported by national funds through Fundação para a Ciência e a Tecnologia (FCT) with references CEECINST/00102/2018, UIDB/00297/2020 and UIDB/00297/2020 (NOVA MATH, Center for Mathematics and Applications), UIDB/04516/2020 (NOVA LINCS), and the research project “MONET – Multi-omic networks in gliomas” (PTDC/CCI-BIO/4180/2020). The results presented are based upon data generated by the TCGA Research Network: https://www.cancer. gov/tcga. Publisher Copyright: © Brazilian Journal of Biometrics.Effective diagnosis and treatment in cancer is a barrier for the development of personalized medicine, mostly due to tumor heterogeneity. In the particular case of gliomas, highly heterogeneous brain tumors at the histological, cellular and molecular levels, and exhibiting poor prognosis, the mechanisms behind tumor heterogeneity and progression remain poorly understood. The recent advances in biomedical high-throughput technologies have allowed the generation of large amounts of molecular information from the patients that combined with statistical and machine learning techniques can be used for the definition of glioma subtypes and targeted therapies, an invaluable contribution to disease understanding and effective management. In this work sparse and robust sparse logistic regression models with the elastic net penalty were applied to glioma RNA-seq data from The Cancer Genome Atlas (TCGA), to identify relevant tran-scriptomic features in the separation between lower-grade glioma (LGG) subtypes and identify putative outlying observations. In general, all classification models yielded good accuracies, selecting different sets of genes. Among the genes selected by the models, TXNDC12, TOMM20, PKIA, CARD8 and TAF12 have been reported as genes with relevant role in glioma development and progression. This highlights the suitability of the present approach to disclose relevant genes and fosters the biological validation of non-reported genes.publishersversionpublishe

Imaging 3D seismic velocity along the seismogenic zone of Algarve region (southern Portugal)

The present seismic tomographic study is focused around Algarve region, in South of Portugal. To locate the seismic events and find the local velocity structure of epicentral area, the P and S arrival times at 38 stations are used. The data used in this study were obtained during the Algarve campaign which worked from January/2006 to July/2007. The preliminary estimate of origin times and hypocentral coordinates are determined by the Hy- poinverse program. Linearized inversion procedure was applied to comprise the following two steps: 1) finding the minimum 1D velocity model using Velest and 2) simultaneous relocation of hypocenters and determination of local velocity structure. The velocity model we have reached is a 10 layer model which gave the lowest RMS, after several runnings of eight different velocity models that we used “a priori”. The model parameterization assumes a continuous velocity field between 4.5 km/s and 7.0 km/s until 30 km depth. The earth structure is represented in 3D by velocity at discrete points, and velocity at any intervening point is determined by linear interpolation among the surrounding eight grid points. A preliminary analysis of the resolution capabilities of the dataset, based on the Derivative Weight Sum (DWS) distribution, shows that the velocity structure is better resolved in the West part of the region between the surface to15 km. The resulting tomographic image has a prominent low-velocity anomaly that shows a maximum decrease in P-wave velocity in the first 12 kms in the studied region. We also identified the occurrence of local seismic events of reduced magnitude not catalogued, in the neighbourhood of Almodôvar (low Alentejo). The spatial distribution of epicentres defines a NE-SW direction that coincides with the strike of the mapped geological faults of the region and issued from photo-interpretation. Is still expectable to refine the seismicity of the region of Almodôvar and establish more rigorously its role in the seismotectonic picture of the region. This work is expected to produce a more detailed knowledge of the structure of the crust over the region of Algarve, being able to identify seismogenic zones, potentially generators of significant seismic events and also the identification of zones of active faults

Long-term survival in a patient with brain metastases of papillary thyroid carcinoma

We present the case of a 43-year-old woman who underwent total thyroidectomy with bilateral lymphadenectomy for a papillary thyroid carcinoma (PTC), solid variant (T4bN1bMx), with V600E BRAF mutation. After ablative therapy, she presented undetectable thyroglobulin (Tg) but progressively increasing anti-Tg antibodies (TgAbs). During follow-up, nodal, lung and brain metastases were identified. She was submitted to surgical excision of lung lesions, radiosurgery of brain metastases and five radioiodine treatments. The latest brain MRI showed no lesions, pulmonary CT showed stable micronodules and there was progressive reduction in TgAbs. This is a peculiar case of a PTC with lung and brain metastatic lesions detected through TgAbs. Initial histological and molecular study suggested a more aggressive clinical behaviour, which was eventually confirmed. Although PTC brain metastases are extremely rare and present poor prognosis, our patient presented a good response to treatment and longer survival than usually reported for similar cases.info:eu-repo/semantics/publishedVersio

Nomear objetos: uma questão de idade?

Poster apresentado no 2º Congresso Internacional de Saúde do Instituto Politécnico de Leiria, 9-10 Maio 2014, Leiria

Spontaneous Intracranial Hypotension and Multi-Level Cervical and Lumbar Epidural Blood Patches: A Case Report

Spontaneous intracranial hypotension (SIH) is a neurologic condition where the intracranial pressure is reduced due to a loss of cerebrospinal fluid from its reservoir, the intrathecal space, to surrounding tissues. It is commonly characterized by an incapacitating headache, phono-photophobia, nausea, and vomiting, commonly refractory to medical treatment and requires further investigation. We describe the case of a healthy young man who presented to the emergency room with a postural headache, accompanied by nausea, vomiting, and phono-photophobia. Brain computed tomography (CT) imaging study was unremarkable and he was initially treated symptomatically. Because of persisting pain even on medical treatment, additional imaging studies, including a myelo-CT scan, were performed and a diagnosis of multi-level cerebrospinal fluid fistulas was made. To treat the underlying cause, a first epidural blood patch (EBP) was initially performed at C7-T1 with 20 mL of autologous blood, but failed to provide complete symptomatic relief. Months later, a second EBP was conducted at C6-C7 with higher volume (30 mL) but as in the first EBP this procedure too did not result in total resolution of the headache and accompanying symptoms. Since there was no surgical indication from Orthopedics and Neurosurgery and the symptoms persisted, a third EBP was carried out, this time at a lumbar level (L2-L3) with infusion of 60 mL of blood so the upper dorsal and cervical epidural space was reached. This resulted in a better symptom relief, allowing the patient to now carry out his normal activities with only residual pain. The need for repeat procedures is one of the pitfalls of the blood patching technique. If possible, it should be performed at the level of the documented fistula, but always with safety in mind and by experienced hands, especially when cervical levels are concerned. A consensus has not been reached regarding the blood volume to be administered; however, any discomfort or pain reported by the patient should be seen as warning sign and the procedure should be interrupted. Although not being a perfect solution, EBP can completely or partially resolve SIH symptoms, without the need for surgical intervention.info:eu-repo/semantics/publishedVersio

Carcinoma da Tiróide em Crianças e Jovens Adultos: Revisão Retrospectiva de 19 Casos

Introduction: Thyroid carcinoma is rare in children and young adults. Most of management guidelines are based in data from adult population. Several controversies remain regarding the aggressiveness of clinical presentation and therapeutic approach. Objective: To evaluate all differentiated thyroid carcinoma patients with less than 20 years-old at presentation reflecting the experience of our unit in relation to diagnosis, treatment and follow-up of this clinical entity. Material and Methods: This is a retrospective review of clinical records of all children and young adults followed at Oncology Consultation of Department of Endocrinology of Centro Hospitalar e Universitário de Coimbra between 1996 and 2012. Results: Nineteen patients with mean age of 16 years old were followed, 13 girls and 6 boys. None of the patients had previous neck irradiation. A palpable cervical mass was the presenting complaint in 84.6%. FNA was performed in 15 patients and was diagnostic or suspicious of malignancy in 71.4%. Total thyroidectomy was performed in 18 cases (94.7%). Papillary carcinoma was identified in all. Vascular invasion and multicentry occurred in 21.1%. Mean tumor size was 2.5cm. Cervical lymph node involvement was diagnosed in 31.6% and distant metastases in 5.2%. The majority of patients (18 in 19) were classified as stage I disease. All patients received thyroxine suppressive therapy and postoperative radioiodine ablation was given to 84.2% (mean dose 85.7mCi). During mean follow-up of almost 6 years, 16 patients remain disease free. Conclusion: In our series, cervical lymph node and distant metastases rates were similar to that found in adult population. Overall prognosis was very good

ShakeMap: Combinação de observações instrumentais e macrossísmicas

Since 2008, the Portuguese seismological service, has implemented the ShakeMap software package provided by U.S. Geological Survey (USGS), in order to obtain reliable maps of peak ground motion parameters and seismic intensities for mainland Portugal. These maps identify the area affected by the earthquake and estimate the severity of ground shaking, thus providing important information for emergency response planning and for the general public. The maps are produced based on regional constraints from instrumental ground motions and site amplifications. In late 2009, USGS released a new version (V3.5) of ShakeMap software with added features. The new approach introduces several changes in the existing ShakeMap methodology, allowing the combination of direct observations (observed peak ground motion and seismic intensities), observations converted parameters and estimates. Some results are presented and discussed in this work