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Stimulus Specificity of Brain-Computer Interfaces Based on Code Modulation Visual Evoked Potentials

by Qingguo Wei, Siwei Feng, Zongwu Lu

A brain-computer interface (BCI) based on code modulated visual evoked potentials (c-VEP) is among the fastest BCIs that have ever been reported, but it has not yet been given a thorough study. In this study, a pseudorandom binary M sequence and its time lag sequences are utilized for modulation of different stimuli and template matching is adopted as the method for target recognition. Five experiments were devised to investigate the effect of stimulus specificity on target recognition and we made an effort to find the optimal stimulus parameters for size, color and proximity of the stimuli, length of modulation sequence and its lag between two adjacent stimuli. By changing the values of these parameters and measuring classification accuracy of the c-VEP BCI, an optimal value of each parameter can be attained. Experimental results of ten subjects showed that stimulus size of visual angle 3.8°, white, spatial proximity of visual angle 4.8° center to center apart, modulation sequence of length 63 bits and the lag of 4 bits between adjacent stimuli yield individually superior performance. These findings provide a basis for determining stimulus presentation of a high-performance c-VEP based BCI system.

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The Course of Pain Intensity in Patients Undergoing Herniated Disc Surgery: A 5-Year Longitudinal Observational Study

by Marie Dorow, Margrit Löbner, Janine Stein, Alexander Pabst, Alexander Konnopka, Hans J. Meisel, Lutz Günther, Jürgen Meixensberger, Katarina Stengler, Hans-Helmut König, Steffi G. Riedel-Heller

Objectives

The aims of this study are to answer the following questions (1) How does the pain intensity of lumbar and cervical disc surgery patients change within a postoperative time frame of 5 years? (2) Which sociodemographic, medical, work-related, and psychological factors are associated with postoperative pain in lumbar and cervical disc surgery patients?

Methods

The baseline survey (T0; n = 534) was conducted 3.6 days (SD 2.48) post-surgery in the form of face-to-face interviews. The follow-up interviews were conducted 3 months (T1; n = 486 patients), 9 months (T2; n = 457), 15 months (T3; n = 438), and 5 years (T4; n = 404) post-surgery. Pain intensity was measured on a numeric rating-scale (NRS 0–100). Estimated changes to and influences on postoperative pain by random effects were accounted by regression models.

Results

Average pain decreased continuously over time in patients with lumbar herniated disc (Wald Chi² = 25.97, p Conclusion

In the majority of disc surgery patients, a long-term reduction of pain was observed. Cervical surgery patients seemed to benefit less from surgery than the lumbar surgery patients. A negative subjective prognosis of gainful employment and stronger depressive symptoms were associated with postoperative pain. The findings may promote multimodal rehabilitation concepts including psychological and work-related support.

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Targeted Next Generation Sequencing in Patients with Inborn Errors of Metabolism

by Dèlia Yubero, Núria Brandi, Aida Ormazabal, Àngels Garcia-Cazorla, Belén Pérez-Dueñas, Jaime Campistol, Antonia Ribes, Francesc Palau, Rafael Artuch, Judith Armstrong, Working Group

Background

Next-generation sequencing (NGS) technology has allowed the promotion of genetic diagnosis and are becoming increasingly inexpensive and faster. To evaluate the utility of NGS in the clinical field, a targeted genetic panel approach was designed for the diagnosis of a set of inborn errors of metabolism (IEM). The final aim of the study was to compare the findings for the diagnostic yield of NGS in patients who presented with consistent clinical and biochemical suspicion of IEM with those obtained for patients who did not have specific biomarkers.

Methods

The subjects studied (n = 146) were classified into two categories: Group 1 (n = 81), which consisted of patients with clinical and biochemical suspicion of IEM, and Group 2 (n = 65), which consisted of IEM cases with clinical suspicion and unspecific biomarkers. A total of 171 genes were analyzed using a custom targeted panel of genes followed by Sanger validation.

Results

Genetic diagnosis was achieved in 50% of patients (73/146). In addition, the diagnostic yield obtained for Group 1 was 78% (63/81), and this rate decreased to 15.4% (10/65) in Group 2 (X2 = 76.171; p Conclusions

A rapid and effective genetic diagnosis was achieved in our cohort, particularly the group that had both clinical and biochemical indications for the diagnosis.

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Are Worry and Rumination Specific Pathways Linking Neuroticism and Symptoms of Anxiety and Depression in Patients with Generalized Anxiety Disorder, Major Depressive Disorder and Mixed Anxiety-Depressive Disorder?

by Hipólito Merino, Carmen Senra, Fátima Ferreiro

This study examines the relationships between neuroticism (higher-order vulnerability factor), the cognitive styles of worry, brooding and reflection (second-order vulnerability factors) and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD), with Major Depressive Disorder (MDD) and with Mixed Anxiety-Depressive Disorder (MADD). One hundred and thirty four patients completed a battery of questionnaires including measures of neuroticism, worry, rumination (brooding and reflection), anxiety and depression. Multiple mediation analyses indicate that worry may act as a mediating mechanism linking neuroticism and anxiety symptoms in the three diagnostic groups, whereas brooding-rumination may play a mediating role between neuroticism and depressive symptoms in patients with MDD and MADD and, with less certainty, in patients with GAD. Overall, our findings suggest that neuroticism may increase the risk of anxious and depressive symptoms via specific links involving either worry or brooding, respectively, and that both worry and brooding may operate in the three groups examined, irrespectively of whether anxiety or depression are the main emotions or whether they coexist without any clear predominance; consequently, we hypothesize the existence of “specific transdiagnostic” mechanisms.

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Identification and Validation of Reference Genes for RT-qPCR Studies of Hypoxia in Squamous Cervical Cancer Patients

by Christina S. Fjeldbo, Eva-Katrine Aarnes, Eirik Malinen, Gunnar B. Kristensen, Heidi Lyng

Hypoxia is an adverse factor in cervical cancer, and hypoxia-related gene expression could be a powerful biomarker for identifying the aggressive hypoxic tumors. Reverse transcription quantitative PCR (RT-qPCR) is a valuable method for gene expression studies, but suitable reference genes for data normalization that are independent of hypoxia status and clinical parameters of cervical tumors are lacking. In the present work, we aimed to identify reference genes for RT-qPCR studies of hypoxia in squamous cervical cancer. From 422 candidate reference genes selected from the literature, we used Illumina array-based expression profiles to identify 182 genes not affected by hypoxia in cervical cancer, i.e. genes regulated by hypoxia in eight cervical cancer cell lines or correlating with the hypoxia-associated dynamic contrast-enhanced magnetic resonance imaging parameter ABrix in 42 patients, were excluded. Among the 182 genes, nine candidates (CHCHD1, GNB2L1, IPO8, LASP1, RPL27A, RPS12, SOD1, SRSF9, TMBIM6) that were not associated with tumor volume, stage, lymph node involvement or disease progression in array data of 150 patients, were selected for further testing by RT-qPCR. geNorm and NormFinder analyses of RT-qPCR data of 74 patients identified CHCHD1, SRSF9 and TMBIM6 as the optimal set of reference genes, with stable expression both overall and across patient subgroups with different hypoxia status (ABrix) and clinical parameters. The suitability of the three reference genes were validated in studies of the hypoxia-induced genes DDIT3, ERO1A, and STC2. After normalization, the RT-qPCR data of these genes showed a significant correlation with Illumina expression (PBrix (PSTC2 data were associated with clinical outcome, in accordance with the Illumina data. Thus, CHCHD1, SRSF9 and TMBIM6 seem to be suitable reference genes for studying hypoxia-related gene expression in squamous cervical cancer samples by RT-qPCR. Moreover, STC2 is a promising prognostic hypoxia biomarker in cervical cancer.

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Dasatinib promotes paclitaxel-induced necroptosis in lung adenocarcinoma with phosphorylated caspase-8 by c-Src

Publication date: 28 August 2016
Source:Cancer Letters, Volume 379, Issue 1
Author(s): Yan Diao, Xiaobin Ma, WeiLi Min, Shuai Lin, HuaFeng Kang, ZhiJun Dai, Xijing Wang, Yang Zhao
Cisplatin and paclitaxel are considered to be the backbone of chemotherapy in lung adenocarcinoma. These agents show pleiotropic effects on cell death. However, the precise mechanisms remain unclear. The present study reported that phosphorylated caspase-8 at tyrosine 380 (p-Casp8) was characterized as a biomarker of chemoresistance to TP regimen (cisplatin and paclitaxel) in patients with resectable lung adenocarcinoma with significantly poorer 5-year disease-free survival (DFS) and overall survival (OS). Cisplatin killed lung adenocarcinoma cells regardless of c-Src-induced caspase-8 phosphorylation at tyrosine 380. Subsequently, we identified a novel mechanism by which paclitaxel induced necroptosis in lung adenocarcinoma cells that was dependent upon p-Casp8, receptor-interacting protein kinase 1 (RIPK1), and RIPK3. Moreover, dasatinib, a c-Src inhibitor, dephosphorylated caspase-8 to facilitate necroptosis, rather than apoptosis, in paclitaxel-treated p-Casp8-expressing lung adenocarcinoma cells. The data from our study revealed previously unrecognized roles of p-Casp8 as a positive effector in the initiation of necroptosis and as a negative effector in the repression of the interaction between RIPK1 and RIPK3. Moreover, these outcomes supported the need for further clinical studies with the goal of evaluating the efficacy of dasatinib plus paclitaxel in the treatment of lung adenocarcinoma.

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