Speech Analysis by Natural Language Processing Techniques: A Possible Tool for Very Early Detection of Cognitive Decline?

Background: The discovery of early, non-invasive biomarkers for the identification of “preclinical” or “pre-symptomatic” Alzheimer's disease and other dementias is a key issue in the field, especially for research purposes, the design of preventive clinical trials, and drafting population-based health care policies. Complex behaviors are natural candidates for this. In particular, recent studies have suggested that speech alterations might be one of the earliest signs of cognitive decline, frequently noticeable years before other cognitive deficits become apparent. Traditional neuropsychological language tests provide ambiguous results in this context. In contrast, the analysis of spoken language productions by Natural Language Processing (NLP) techniques can pinpoint language modifications in potential patients. This interdisciplinary study aimed at using NLP to identify early linguistic signs of cognitive decline in a population of elderly individuals.Methods: We enrolled 96 participants (age range 50–75): 48 healthy controls (CG) and 48 cognitively impaired participants: 16 participants with single domain amnestic Mild Cognitive Impairment (aMCI), 16 with multiple domain MCI (mdMCI) and 16 with early Dementia (eD). Each subject underwent a brief neuropsychological screening composed by MMSE, MoCA, GPCog, CDT, and verbal fluency (phonemic and semantic). The spontaneous speech during three tasks (describing a complex picture, a typical working day and recalling a last remembered dream) was then recorded, transcribed and annotated at various linguistic levels. A multidimensional parameter computation was performed by a quantitative analysis of spoken texts, computing rhythmic, acoustic, lexical, morpho-syntactic, and syntactic features.Results: Neuropsychological tests showed significant differences between controls and mdMCI, and between controls and eD participants; GPCog, MoCA, PF, and SF also discriminated between controls and aMCI. In the linguistic experiments, a number of features regarding lexical, acoustic and syntactic aspects were significant in differentiating between mdMCI, eD, and CG (non-parametric statistical analysis). Some features, mainly in the acoustic domain also discriminated between CG and aMCI.Conclusions: Linguistic features of spontaneous speech transcribed and analyzed by NLP techniques show significant differences between controls and pathological states (not only eD but also MCI) and seems to be a promising approach for the identification of preclinical stages of dementia. Long duration follow-up studies are needed to confirm this assumption

Abnormal Circadian Modification of A\u3b4-Fiber Pathway Excitability in Idiopathic Restless Legs Syndrome

Restless legs syndrome (RLS) is characterized by unpleasant sensations generally localized to legs, associated with an urge to move. A likely pathogenetic mechanism is a central dopaminergic dysfunction. The exact role of pain system is unclear. The purpose of the study was to investigate the nociceptive pathways in idiopathic RLS patients. We enrolled 11 patients (mean age 53.2\u2009\ub1\u200919.7 years; 7 men) suffering from severe, primary RLS. We recorded scalp laser-evoked potentials (LEPs) to stimulation of different sites (hands and feet) and during two different time conditions (daytime and nighttime). Finally, we compared the results with a matched control group of healthy subjects. The A\u3b4 responses obtained from patients did not differ from those recorded from control subjects. However, the N1 and the N2-P2 amplitudes' night/day ratios after foot stimulation were increased in patients, as compared to controls (N1: patients: 133.91\u2009\ub1\u200950.42%; controls: 83.74\u2009\ub1\u200934.45%; p = 0.016; A\u3b4-N2-P2: patients: 119.15\u2009\ub1\u200915.56%; controls: 88.42\u2009\ub1\u200923.41%; p = 0.003). These results suggest that RLS patients present circadian modifications in the pain system, which are not present in healthy controls. Both sensory-discriminative and affective-emotional components of pain experience show parallel changes. This study confirms the structural integrity of A\u3b4 nociceptive system in idiopathic RLS, but it also suggests that RLS patients present circadian modifications in the pain system. These findings could potentially help clinicians and contribute to identify new therapeutic approaches

Preclinical Evidence of Progesterone as a New Pharmacological Strategy in Human Adrenocortical Carcinoma Cell Lines

BACKGROUND Adrenocortical cancer (ACC) is a rare malignancy with a dismal prognosis. The treatment includes mitotane and EDP chemotherapy (etoposide, doxorubicin, and cisplatin). However, new therapeutic approaches for advanced ACC are needed, particularly targeting the metastatic process. Here, we deepen the role of progesterone as a new potential drug for ACC, in line with its antitumoral effect in other cancers. METHODS NCI-H295R, MUC-1, and TVBF-7 cell lines were used and xenografted in zebrafish embryos. Migration and invasion were studied using transwell assays, and MMP2 activity was studied using zymography. Apoptosis and cell cycle were analyzed by flow cytometry. RESULTS Progesterone significantly reduced xenograft tumor area and metastases formation in embryos injected with metastatic lines, MUC-1 and TVBF-7. These results were confirmed in vitro, where the reduction of invasion was mediated, at least in part, by the decrease in MMP2 levels. Progesterone exerted a long-lasting effect in metastatic cells. Progesterone caused apoptosis in NCI-H295R and MUC-1, inducing changes in the cell-cycle distribution, while autophagy was predominantly activated in TVBF-7 cells. CONCLUSION Our results give support to the role of progesterone in ACC. The involvement of its analog (megestrol acetate) in reducing ACC progression in ACC patients undergoing EDP-M therapy is now under investigation in the PESETA phase II clinical study

The moderator effect of perceived risk in other consumer perception (OCP)

Este artigo analisa a percepção dos indivíduos em relação aos outros consumidores presentes no ambiente de compras (OCP) e a sua influência no processo decisório desses consumidores. Além disso, examina o efeito moderador do Risco Percebido nas relações entre a OCP e a Evitação e a Aproximação. Oito hipóteses foram desenvolvidas com base na literatura e testadas por meio da análise dos dados oriundos de um survey, no qual participaram 456 estudantes universitários. A técnica de análise realizada foi a modelagem de equações estruturais com estimação pelos mínimos quadrados parciais. Como resultados, foi comprovada a relação positiva da OCP com o comportamento de Aproximação e a relação negativa com o comportamento de Evitação. Os resultados identificaram também o efeito moderador do risco percebido positivo entre a OCP e a Aproximação e negativo entre a OCP e a Evitação.Palavras-chave: OCP, risco percebido, varejo.This article analyzes individual perception in relation to other consumers present in shopping environment (OCP) and its influence in the decision-making process of these consumers. In addition, it examines the moderator effect of Perceived Risk in relations among OCP, Avoidance and Approximation. Eight hypotheses were developed based on literature and tested by analysis of data from a survey, in which 456 college students participated. The analysis technique used was structural equations modeling with estimations for the partial least square. As a result, a positive relation between OCP and Approximation behavior and a negative relation between OCP and Avoidance behavior were proven. The results also identified a positive moderator effect of perceived risk between OCP and Approximation and a negative effect between OCP and Avoidance.Keywords: OCP, perceived risk, retail

Multiple large osteolytic lesions in a patient with systemic mastocytosis: a challenging diagnosis

Patients with advanced variants of Systemic Mastocytosis may develop destructive bone lesions when massive mast cell (MC) infiltrates are present. Finding of large osteolyses in indolent systemic mastocytosis, typically characterized by low MC burden, should prompt investigations for an alternative explanation

O efeito moderador do risco percebido na percepção dos outros consumidores (OCP – other consumer perception)

This article analyzes individual perception in relation to other consumers present in shopping environment (OCP) and its influence in the decision-making process of these consumers. In addition, it examines the moderator effect of Perceived Risk in relations among OCP, Avoidance and Approximation. Eight hypotheses were developed based on literature and tested by analysis of data from a survey, in which 456 college students participated. The analysis technique used was structural equations modeling with estimations for the partial least square. As a result, a positive relation between OCP and Approximation behavior and a negative relation between OCP and Avoidance behavior were proven. The results also identified a positive moderator effect of perceived risk between OCP and Approximation and a negative effect between OCP and Avoidance.Keywords: OCP, perceived risk, retail.Este artigo analisa a percepção dos indivíduos em relação aos outros consumidores presentes no ambiente de compras (OCP) e a sua influência no processo decisório desses consumidores. Além disso, examina o efeito moderador do Risco Percebido nas relações entre a OCP e a Evitação e a Aproximação. Oito hipóteses foram desenvolvidas com base na literatura e testadas por meio da análise dos dados oriundos de um survey, no qual participaram 456 estudantes universitários. A técnica de análise realizada foi a modelagem de equações estruturais com estimação pelos mínimos quadrados parciais. Como resultados, foi comprovada a relação positiva da OCP com o comportamento de Aproximação e a relação negativa com o comportamento de Evitação. Os resultados identificaram também o efeito moderador do risco percebido positivo entre a OCP e a Aproximação e negativo entre a OCP e a Evitação.Palavras-chave: OCP, risco percebido, varejo

FSCN1 as a new druggable target in adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a high risk of relapse and metastatic spread. The actin-bundling protein fascin (FSCN1) is overexpressed in aggressive ACC and represents a reliable prognostic indicator. FSCN1 has been shown to synergize with VAV2, a guanine nucleotide exchange factor for the Rho/Rac GTPase family, to enhance the invasion properties of ACC cancer cells. Based on those results, we investigated the effects of FSCN1 inactivation by CRISPR/Cas9 or pharmacological blockade on the invasive properties of ACC cells, both in vitro and in an in vivo metastatic ACC zebrafish model. Here, we showed that FSCN1 is a transcriptional target for β-catenin in H295R ACC cells and that its inactivation resulted in defects in cell attachment and proliferation. FSCN1 knock-out modulated the expression of genes involved in cytoskeleton dynamics and cell adhesion. When Steroidogenic Factor-1 (SF-1) dosage was upregulated in H295R cells, activating their invasive capacities, FSCN1 knock-out reduced the number of filopodia, lamellipodia/ruffles and focal adhesions, while decreasing cell invasion in Matrigel. Similar effects were produced by the FSCN1 inhibitor G2-044, which also diminished the invasion of other ACC cell lines expressing lower levels of FSCN1 than H295R. In the zebrafish model, metastases formation was significantly reduced in FSCN1 knock-out cells and G2-044 significantly reduced the number of metastases formed by ACC cells. Our results indicate that FSCN1 is a new druggable target for ACC and provide the rationale for future clinical trials with FSCN1 inhibitors in patients with ACC

Utilização da técnica de repetição espaçada na aprendizagem da anatomia humana / Use of spaced repetition technique in learning human anatomy

A disciplina de Anatomia é uma ciência com conteúdo difícil de memorizar, principalmente pela quantidade e complexidade de sua terminologia. Dentre as técnicas que auxiliam a manter a informação aprendida por mais tempo ou evocá-la com facilidade, o sistema de repetição espaçada (SRE) tem se mostrado eficaz como método de revisão de conteúdo que potencializa a retenção da memória. Assim, o objetivo deste trabalho foi avaliar a utilização do SRE e compará-lo com a metodologia tradicional de ensino em Anatomia Humana sem revisão sistematizada. Participaram da pesquisa 28 alunos do curso de Enfermagem da Universidade Federal de Uberlândia. Durante 16 semanas, os estudantes tiveram aulas teóricas e práticas expositivas de Anatomia e fizeram revisões extraclasse individuais utilizando a técnica SRE com o apoio do programa Anki, empregando cartões de repetição espaçada. Para avaliar o método, foram analisados os cartões aprendidos, reaprendidos, revisados e estudados, e foram comparadas as notas parciais e final com uma turma que não utilizou o método. Os resultados demostraram que a média dos cartões aprendidos foi 39,41% dos cartões disponibilizados; 50% dos estudantes não reaprendeu nenhum cartão; 67,85% dos estudantes revisaram uma quantidade de cartões abaixo da média da turma; a média dos cartões estudados foi 41,07% dos cartões disponibilizados; a turma que utilizou o método SRE apresentou nota significativamente maior apenas em uma das notas parciais. Assim, pode-se concluir que a adesão ao método SRE foi insatisfatória e não forneceu evidências da sua eficiência na maximização da aprendizagem. Contudo, comparado a metodologia tradicional sem revisão sistematizada, se mostrou eficaz apenas a longo prazo