Thomsonneumann4046

BACKGROUND Many functional analysis tools have been developed to extract functional and mechanistic insight from bulk transcriptome data. With the advent of single-cell RNA sequencing (scRNA-seq), it is in principle possible to do such an analysis for single cells. However, scRNA-seq data has characteristics such as drop-out events and low library sizes. It is thus not clear if functional TF and pathway analysis tools established for bulk sequencing can be applied to scRNA-seq in a meaningful way. RESULTS To address this question, we perform benchmark studies on simulated and real scRNA-seq data. We include the bulk-RNA tools PROGENy, GO enrichment, and DoRothEA that estimate pathway and transcription factor (TF) activities, respectively, and compare them against the tools SCENIC/AUCell and metaVIPER, designed for scRNA-seq. For the in silico study, we simulate single cells from TF/pathway perturbation bulk RNA-seq experiments. We complement the simulated data with real scRNA-seq data upon CRISPR-mediated knock-out. Our benchmarks on simulated and real data reveal comparable performance to the original bulk data. Additionally, we show that the TF and pathway activities preserve cell type-specific variability by analyzing a mixture sample sequenced with 13 scRNA-seq protocols. We also provide the benchmark data for further use by the community. CONCLUSIONS Our analyses suggest that bulk-based functional analysis tools that use manually curated footprint gene sets can be applied to scRNA-seq data, partially outperforming dedicated single-cell tools. Furthermore, we find that the performance of functional analysis tools is more sensitive to the gene sets than to the statistic used.BACKGROUND Sexual concerns are distressing for breast cancer survivors and interfere with their intimate relationships. This study evaluates the efficacy of a four-session couple-based intervention delivered via telephone, called Intimacy Enhancement (IE). The IE intervention is grounded in social cognitive theory and integrates evidence-based techniques from cognitive behavioral couple therapy and sex therapy to address survivors' sexual concerns and enhance their and their partners' sexual, relationship, and psychological outcomes. METHODS This trial is designed to evaluate the efficacy of the IE intervention in improving survivors' sexual function, the primary study outcome. Secondary outcomes include survivors' sexual distress, partners' sexual function, and survivors' and partners' relationship intimacy and quality as well as psychological distress (depressive symptoms and anxiety symptoms). Additional aims are to examine whether treatment effects on patient sexual function are mediated by sexual communiel couple-based intervention delivered via telephone for breast cancer survivors experiencing sexual concerns and their intimate partners, in comparison with an attention control. Findings of this study could influence clinical care for women with breast cancer and inform theory guiding cancer-related sexual rehabilitation. TRIAL REGISTRATION ClinicalTrials.gov, NCT03930797. Registered on 24 April 2019.Synaptic proteins play an important role for the regulation of synaptic plasticity. Numerous studies have identified and revealed individual synaptic protein functions using protein overexpression or deletion. In neuropathic pain nociceptive stimuli conveyed from the periphery repetitively stimulate neurons in the central nerve system, brain and spinal cord. Neuronal activities change the turnover (synthesis and degradation) rate of synaptic proteins. Thus, the analysis of synaptic protein turnover rather than just expression level change is critical for studying the role of synaptic proteins in synaptic plasticity. Here, we analyzed synaptosomal proteome in the anterior cingulate cortex (ACC) to identify protein turnover rate changes caused by peripheral nerve injury. Whereas PKCγ levels were not altered, we found that the protein's turnover rate decreased after peripheral nerve injury. Our results suggest that postsynaptic PKCγ synthesized by neuronal activities in the ACC is translocated to the postsynaptic membrane with an extended half-life.Structural variants (SVs) remain challenging to represent and study relative to point mutations despite their demonstrated importance. We show that variation graphs, as implemented in the vg toolkit, provide an effective means for leveraging SV catalogs for short-read SV genotyping experiments. We benchmark vg against state-of-the-art SV genotypers using three sequence-resolved SV catalogs generated by recent long-read sequencing studies. selleck kinase inhibitor In addition, we use assemblies from 12 yeast strains to show that graphs constructed directly from aligned de novo assemblies improve genotyping compared to graphs built from intermediate SV catalogs in the VCF format.BACKGROUND Several surgical reconstructive options are available to treat massive rotator cuff tears (MRCTs). The rotator cable has an important function and we evaluated the clinical result after arthroscopic reconstruction of the rotator cable with an autograft tendon. METHODS A prospective pilot study was performed with inclusion of four patients, average age of 64 years, with an irreparable MRCT. The patients underwent an arthroscopic reconstruction of the rotator cable with the use of the long head of biceps tendon autograft, except for one which was reconstructed with a hamstring tendon. Pre- and postsurgically, the Constant-Murley Score (CMS), Western Ontario Rotator Cuff Index (WORC), Simple Shoulder Test (SST), visual analog scale (VAS) scores, and an MRI was performed. Clinical results of the study group were compared with clinical results of comparable cohort of patients with a MRCT, treated non-operatively with physiotherapy. RESULTS The CMS score increased after surgery in three of the four patients. The improvement of CMS score was comparable to the improvement of the CMS score encountered in a comparable cohort. The MRI at 12 months follow-up showed that the reconstructed rotator cable was disintegrated in all patients and the rotator cuff was detached and retracted. CONCLUSIONS In our pilot study, arthroscopic reconstruction of the rotator cable using a tendon autograft failed over time and showed no clinical benefit in comparison to the non-operative treatment with physiotherapy. TRIAL REGISTRATION The regional Medical Ethical Committee (Zwolle) gave approval at 14th of October 2016 and assigned no. 16.06100.BACKGROUND The pathophysiological etiologies related with the development of Autism Spectrum Disorders (ASD) remain controversial. Different authors have studied neurotoxins such as mercury (Hg) and their relationship with ADS. The objective of this study was to assess the levels of Hg in hair in a group of ASD children (chronic exposure) and in urinary excretion (acute exposure), in comparison to a healthy group. METHODS A case-control study was conducted in Spanish children. We compared 54 ASD children (aged 2-6) with no other associated pathology to a normally-developing control group (54 subjects). RESULTS There were no differences in urine (p0.631) and hair (p1.000) samples percentages below the limits of detection between the control and the ASD groups, and also between patients in the regression ASD subgroup (AMR) (p0.08) and the non-regression ASD subgroup (ANMR) (p0.705). When the analysis was adjusted for age and sex, the differences between Hg levels maintained not significant. There were no correlations between Hg concentrations in the ASD group as a whole (p 0.739), or when they were subdivided into ASD-AMR (p 0.739) and ASD-ANMR (p 0.363). CONCLUSIONS The present study shows no evidence in our geographical area to support an association between mercury neurotoxicity and the etiopathogenesis of ASD.BACKGROUND Neonatal acidaemia at birth can increase neonatal morbidity and mortality and it is predictive of neonatal asphyxia. The umbilical blood gas analysis is a valid tool for the evaluation of neonatal acidaemia. However, umbilical cord blood gas analysis is commonly performed in high-risk situations or in the setting of Apgar scores  6 mmol/l. The aim was to evaluate the predictive role of blood gas analysis for respiratory distress syndrome in newborns with reassuring Apgar Score. RESULTS 352 full term newborns were enrolled. Umbilical cord blood artery pH showed an association with respiratory distress syndrome (χ2(1) = 10,084, OR (95% CI) 3,9 × 10- 4(2,9 × 10- 6 - 0,048); p  less then  0,05). ROC curve revealed that the cut-off point of pH was 7.12, with a sensibility and specificity of 68 and 63%, respectively. CONCLUSIONS Umbilical cord blood artery pH  less then  7.12 at birth is associated to respiratory distress syndrome in newborns. Blood gas analysis is an important instrument to help health care providers during assistance in the delivery room, but also to early identify newborns at high risk for respiratory distress syndrome and better manage the care of these newborns after birth.BACKGROUND Food labelling is a common intervention to improve diets, where the back-of-pack Nutrition Information Panel (or Nutrition Facts table (NFt)) provides comprehensive nutrition information on food packages. However, many consumers find it difficult and time-consuming to identify healthier foods using the NFt. As a result, different interpretative nutrition rating systems (INRS) may enable healthier food choices and it is essential that consumers have the tools to allow for easily accessible nutrition information. The objective of this study was to examine consumers' perceptions of different (INRS) for delivery of nutrition information using different versions of a smartphone app, FoodFlip©. METHODS This study was part of a larger randomized controlled trial examining consumer perceptions of different INRS on food products. A nationally representative commercial sample of 2008 Canadians were randomized to one of four INRS intervention groups 1) traffic light, 2) health star rating, 3) 'high-in' warninability to compare the healthfulness of products (p  less then  0.001). CONCLUSION This study demonstrated Canadian consumers' preference for a nutrient-specific system (i.e. traffic light or 'high-in' warning labels). The app, which was liked by majority of the participants for its functionality and usability, has the potential to support healthy dietary decision making and may also encourage reformulation. TRIAL REGISTRATION NCT03290118 (Clinicaltrials.gov).OBJECTIVE The aim of this study is to establish a noninvasive preoperative model for predicting primary optimal cytoreduction in advanced epithelial ovarian cancer by HE4 and CA125 combined with clinicopathological parameters. METHODS Clinical data including preoperative serum HE4 and CA125 level of 83 patients with advanced epithelial ovarian cancer were collected. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of each clinical parameter were calculated. The Predictive Index score model and the logistic model were constructed to predict the primary optimal cytoreduction. RESULTS Optimal surgical cytoreduction was achieved in 62.65% (52/83) patients. Cutoff values of preoperative serum HE4 and CA125 were 777.10 pmol/L and 313.60 U/ml. (1) Patients with PIV ≥ 6 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing suboptimal cytoreduction were 71, 100, 68, and 100%, respectively. (2) The logistic model was logit p = 0.