Preface

Cancer and Metastasis Reviews -     

Electrophysiology of statistical learning: Exploring the online learning process and offline learning product

A continuous stream of syllables is segmented into discrete constituents based on the transitional probabilities (TPs) between adjacent syllables by means of statistical learning. However, we still do not know whether people attend to high TPs between frequently co‐occurring syllables and cluster them together as parts of the discrete constituents or attend to low TPs aligned with the edges between the constituents and extract them as whole units. Earlier studies on TP‐based segmentation also have not distinguished between the segmentation process (how people segment continuous speech) and the learning product (what is learnt by means of statistical learning mechanisms). In the current study, we explored the learning outcome separately from the learning process, focusing on three possible learning products: holistic constituents that are retrieved from memory during the recognition test, clusters of frequently co‐occurring syllables, or a set of statistical regularities which can be used to reconstruct legitimate candidates for discrete constituents during the recognition test. Our data suggest that people employ boundary‐finding mechanisms during online segmentation by attending to low inter‐syllabic TPs during familiarization and also identify potential candidates for discrete constituents based on their statistical congruency with rules extracted during the learning process. Memory representations of recurrent constituents embedded in the continuous speech stream during familiarization facilitate subsequent recognition of these discrete constituents.     

Determining the utility of a smartphone-based gait evaluation for possible use in concussion management

ABSTRACT

Objectives: Our was objectives were to (1) assess the validity of a smartphone-based application to obtain spatiotemporal gait variables relative to an established movement monitoring system used previously to evaluate post-concussion gait, and (2) determine the test-retest reliability of gait variables obtained with a smartphone.

Methods: Twenty healthy participants (n = 14 females, mean age = 22.2, SD = 2.1 years) were assessed at two time points, approximately two weeks apart. Two measurement systems (inertial sensor system, smartphone application) acquired and analyzed single-task and dual-task spatio-temporal gait variables simultaneously. Our primary outcome measures were average walking speed (m/s), cadence (steps/min), and stride length (m) measured by the inertial sensor system and smartphone application.

Results: Correlations between the systems were high to very high (Pearson r = 0.77–0.98) at both time points, with the exception of dual-task stride length at time 2 (Pearson r = 0.55). Bland-Altman analysis for average gait speed and cadence indicated the average disagreement between systems was close to zero, suggesting little evidence for systematic bias between acquisition systems. Test-retest consistency measures using the smartphone revealed high to very high reliability for all measurements (ICC = 0.81–0.95).

Conclusions: Our results indicate that sensors within a smartphone are capable of measuring spatio-temporal gait variables similar to a validated three-sensor inertial sensor system in single-task and dual-task conditions, and that data are reliable across a two-week time interval. A smartphone-based application might allow clinicians to objectively evaluate gait in the management of concussion with high ease-of-use and a relatively low financial burden.     

The role of polo-like kinase 3 in the response of BRAF-mutant cells to targeted anticancer therapies

The activation of oncogenic mitogen-activated protein kinase cascade via mutations in BRAF is often observed in human melanomas. Targeted inhibitors of BRAF (BRAFi), alone or as a part of a combination therapy, offer a significant benefit to such patients. Unfortunately, some cases are initially nonresponsive to these drugs, while others become refractory in the course of treatment, underscoring the need to understand and mitigate the underlying resistance mechanisms. We report that interference with polo-like kinase 3 (PLK3) reduces the tolerance of BRAF-mutant melanoma cells to BRAFi, while increased PLK3 expression has the opposite effect. Accordingly, PLK3 expression correlates with tolerance to BRAFi in a panel of BRAF-mutant cell lines and is elevated in a subset of recurring BRAFi-resistant melanomas. In PLK3-expressing cells, R406, a kinase inhibitor whose targets include PLK3, recapitulates the sensitizing effects of genetic PLK3 inhibitors. The findings support a role for PLK3 as a predictor of BRAFi efficacy and suggest suppression of PLK3 as a way to improve the efficacy of targeted therapy.     

Noncompaction cardiomyopathy is caused by a novel in‐frame desmin (DES) deletion mutation within the 1A coiled‐coil rod segment leading to a severe filament assembly defect

Mutations in DES, encoding desmin protein, are associated with different kinds of skeletal and/or cardiac myopathies. However, it is unknown, whether DES mutations are associated with left ventricular hypertrabeculation (LVHT). Here, we performed a clinical examination and subsequent genetic analysis in a family, with two individuals presenting LVHT with conduction disease and skeletal myopathy. The genetic analysis revealed a novel small in‐frame deletion within the DES gene, p.Q113_L115del, affecting the α‐helical rod domain. Immunohistochemistry analysis of explanted myocardial tissue from the index patient revealed an abnormal cytoplasmic accumulation of desmin and a degraded sarcomeric structure. Cell transfection experiments with wild‐type and mutant desmin verified the cytoplasmic aggregation and accumulation of mutant desmin. Cotransfection experiments were performed to model the heterozygous state of the patients and revealed a dominant negative effect of the mutant desmin on filament assembly. DES:p.Q113_L115del is classified as a pathogenic mutation associated with dilated cardiomyopathy with prominent LVHT.     

A Novel Prefabricated Grid for Guided Endodontic Microsurgery

Introduction

This study aimed to introduce a novel method using cone-beam computed tomographic (CBCT) imaging and prefabricated grids to guide apical access during endodontic microsurgery and to compare its accuracy with that of the nonguided method.

Genetic polymorphisms in NQO1 and SOD2: Interactions with smoking,schistosoma infection,and bladder cancer risk in Egypt

BackgroundBladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms in NAD(P)H:quinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individual's susceptibility to these carcinogenic exposures and hence the risk of bladder cancer.MethodsWe assessed the effects of potential interactions between functional polymorphisms in the NQO1 and SOD2 genes and exposure to smoking and SH infection on bladder cancer risk among 902 cases and 804 population-based controls in Egypt. We used unconditional logistic regression to estimate the odds ratios (OR) and confidence intervals (CI) 95%.ResultsWater pipe and cigarette smoking were more strongly associated with cancer risk among individuals with the TT genotype for SOD2 (OR [CI 95%] = 4.41 [1.86–10.42]) as compared with those with the CC genotype (OR [CI 95%] = 2.26 [0.97–6.74]). Conversely, the risk associated with SH infection was higher among the latter (OR [CI 95%] = 3.59 [2.21–5.84]) than among the former (OR [CI 95%] = 1.86 [1.33–2.60]). Polymorphisms in NQO1 genotype showed a similar pattern, but to a much lesser extent. The highest odds for having bladder cancer following SH infection were observed among individuals with the CC genotypes for both NQO1 and SOD2 (OR [CI 95%] = 4.41 [2.32–8.38]).ConclusionOur findings suggest that genetic polymorphisms in NQO1 and SOD2 play important roles in the etiology of bladder cancer by modulating the effects of known contributing factors such as smoking and SH infection.