Transcranial direct current stimulation in neglect rehabilitation after stroke: a systematic review.

Hemispatial neglect is one of the most frequent attention disorders after stroke. The presence of neglect is associated with longer hospital stays, extended rehabilitation periods, and poorer functional recovery. Transcranial direct current stimulation (tDCS) is a new technique with promising results in neglect rehabilitation; therefore, the objective of this systematic review, performed following the PRISMA guidelines, is to evaluate the effectiveness of tDCS on neglect recovery after stroke. The search was done in MEDLINE (PubMed), Web of Science, Scopus, Cochrane Library, and BioMed Central databases. A total of 311 articles were found; only 11 met the inclusion criteria, including 152 post-stroke patients in total. Methodological quality and risk of bias were assessed for all the studies, and methodological characteristics of the studies, sample sizes, methods, main results, and other relevant data were extracted. tDCS intervention ranged from one to twenty sessions distributed in 1 day to 4 weeks, with intensity ranged from 1 to 2 mA. We found moderate evidence for the efficacy of tDCS in the rehabilitation of hemispatial neglect after a stroke, being more effective in combination with other interventions. Nonetheless, the limited number of studies and some studies' design characteristics makes it risky to draw categorical conclusions. Since scientific evidence is still scarce, further research is needed to determine the advantage of this treatment in acute, sub-acute and chronic stroke patients. Future studies should include larger samples, longer follow-ups, and broader neurophysiological assessments, with the final aim of establishing the appropriate use of tDCS as an adjuvant intervention in neurorehabilitation settings.pre-print964 K

Longitudinal association of inflammatory markers with markers of glycaemia and insulin resistance in European children

Purpose: Subclinical systemic inflammation may lead to development of type 2 diabetes, but there has been no investigation into its relationship with early progression of glycaemic deterioration and insulin resistance, especially in younger population. In this study we assessed longitudinal associations of pro- and anti-inflammatory markers with markers that evaluate glycaemia and insulin resistance. Methods: This study includes 6537 initially nondiabetic children (mean age at baseline = 6.2 years) with repeated measurements from the IDEFICS/I.Family cohort study (mean follow-up = 5.3 years) from eight European countries. Markers of inflammation were used as independent variables and markers of glycaemia/insulin resistance as dependent variables. Associations were examined using two-level growth model. Models were adjusted for sex, age, major lifestyle, metabolic risk factors, early life markers, and other inflammatory markers in final model. Results: Children with 6 years of follow-up showed that a one-unit increase in z-score of leptin level was associated with 0.38 (95% CI = 0.32 to 0.44) unit increase in HOMA-IR z-scores. Leptin continued to be associated with HOMA-IR even when analysis was limited to children with no overall obesity, no abdominal obesity, and low to normal triglyceride levels. An inverse association was observed between IL-15 and HOMA-IR (ß = -0.11, 95% CI = -0.15 to -0.07). Conclusions: IL-15 should be evaluated further in the prevention or treatment of prediabetes whereas leptin may prove to be useful in early detection of prediabetes via their association with markers of insulin resistance in European children

BlackOPs: Increasing confidence in variant detection through mappability filtering

Identifying variants using high-throughput sequen-cing data is currently a challenge because true biological variants can be indistinguishable from technical artifacts. One source of technical arti-fact results from incorrectly aligning experimen-tally observed sequences to their true genomic origin (‘mismapping’) and inferring differences in mismapped sequences to be true variants. We de-veloped BlackOPs, an open-source tool that simu-lates experimental RNA-seq and DNA whole exome sequences derived from the reference genome, aligns these sequences by custom parameters, detects variants and outputs a blacklist of positions and alleles caused by mismapping. Blacklist

SigFuge: Single gene clustering of RNA-seq reveals differential isoform usage among cancer samples

High-throughput sequencing technologies, including RNA-seq, have made it possible to move beyond gene expression analysis to study transcriptional events including alternative splicing and gene fusions. Furthermore, recent studies in cancer have suggested the importance of identifying transcriptionally altered loci as biomarkers for improved prognosis and therapy. While many statistical methods have been proposed for identifying novel transcriptional events with RNA-seq, nearly all rely on contrasting known classes of samples, such as tumor and normal. Few tools exist for the unsupervised discovery of such events without class labels. In this paper, we present SigFuge for identifying genomic loci exhibiting differential transcription patterns across many RNA-seq samples. SigFuge combines clustering with hypothesis testing to identify genes exhibiting alternative splicing, or differences in isoform expression. We apply SigFuge to RNA-seq cohorts of 177 lung and 279 head and neck squamous cell carcinoma samples from the Cancer Genome Atlas, and identify several cases of differential isoform usage including CDKN2A, a tumor suppressor gene known to be inactivated in a majority of lung squamous cell tumors. By not restricting attention to known sample stratifications, SigFuge offers a novel approach to unsupervised screening of genetic loci across RNA-seq cohorts. SigFuge is available as an R package through Bioconductor

SWISS MADE: Standardized WithIn Class Sum of Squares to Evaluate Methodologies and Dataset Elements

Contemporary high dimensional biological assays, such as mRNA expression microarrays, regularly involve multiple data processing steps, such as experimental processing, computational processing, sample selection, or feature selection (i.e. gene selection), prior to deriving any biological conclusions. These steps can dramatically change the interpretation of an experiment. Evaluation of processing steps has received limited attention in the literature. It is not straightforward to evaluate different processing methods and investigators are often unsure of the best method. We present a simple statistical tool, Standardized WithIn class Sum of Squares (SWISS), that allows investigators to compare alternate data processing methods, such as different experimental methods, normalizations, or technologies, on a dataset in terms of how well they cluster a priori biological classes. SWISS uses Euclidean distance to determine which method does a better job of clustering the data elements based on a priori classifications. We apply SWISS to three different gene expression applications. The first application uses four different datasets to compare different experimental methods, normalizations, and gene sets. The second application, using data from the MicroArray Quality Control (MAQC) project, compares different microarray platforms. The third application compares different technologies: a single Agilent two-color microarray versus one lane of RNA-Seq. These applications give an indication of the variety of problems that SWISS can be helpful in solving. The SWISS analysis of one-color versus two-color microarrays provides investigators who use two-color arrays the opportunity to review their results in light of a single-channel analysis, with all of the associated benefits offered by this design. Analysis of the MACQ data shows differential intersite reproducibility by array platform. SWISS also shows that one lane of RNA-Seq clusters data by biological phenotypes as well as a single Agilent two-color microarray

Rapid clearance profile of plasma circulating tumor HPV type 16 DNA during chemoradiotherapy correlates with disease control in HPV-associated oropharyngeal cancer

Purpose: To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Experimental Design: A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16- positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits. Optimized multianalyte digital PCR assays were used to quantify ctHPVDNA (types 16/18/31/33/35) in plasma. A control cohort of 55 healthy volunteers and 60 patients with non-HPV-associated malignancy was also analyzed. Results: Baseline plasma ctHPVDNA had high specificity (97%) and high sensitivity (89%) for detecting newly diagnosed HPV-associated OPSCC. Pretreatment ctHPV16DNA copy number correlated with disease burden, tumor HPV copy number, and HPV integration status. We define a ctHPV16DNA favorable clearance profile as having high baseline copy number (>200 copies/mL) and >95% clearance of ctHPV16DNA by day 28 of CRT. Nineteen of 67 evaluable patients had a ctHPV16DNA favorable clearance profile, and none had persistent or recurrent regional disease after CRT. In contrast, patients with adverse clinical risk factors (T4 or >10 pack years) and an unfavorable ctHPV16DNA clearance profile had a 35% actuarial rate of persistent or recurrent regional disease after CRT (P = 0.0049). Conclusions: A rapid clearance profile of ctHPVDNA may predict likelihood of disease control in patients with HPVassociated OPSCC patients treated with definitive CRT and may be useful in selecting patients for deintensified therapy

Patient reported outcomes (PROS) in psoriasis patients

P20 Introduction: Psoriasis is a chronic skin disease with negative physical, mental and social manifestations. Method: We carried out a longitudinal and prospective study under routine clinical practice conditions. The objective of the study was to measure quality of life with the Short Form-36 Survey (SF-36) and correlate the results with clinical variables using the PASI and BSA in a group of 17 patients with moderate to severe psoriasis treated with Ustekinumab. Results: In the baseline evaluation we observed the following results: 35.3% reported physical malfunction, 64.7% debilitating pain, 82.3% poor health in general, 76.4% bad vitality, 88.2% social malfunction, 100% emotional malfunction and 82.3% poor mental health. At week 78 we observed the following results: 41.15% reported very good physical functioning, 76.1% no pain, 58.8% good general health, 58.8% very good vitality, 70%, 5% good social functioning, 70.5% good emotional functioning and 52.9% good mental health. Conclusion: We observed that the perception of patients with moderate-severe psoriasis regarding their health at the beginning of treatment with Ustekinumab was poor and that they experienced a significant improvement throughout the successive weeks of treatment