Search

Context Pituitary apoplexy (PA) has been traditionally considered a neurosurgical emergency, yet retrospective single-institution studies suggest similar outcomes among patients managed medically. Objective We established a multicenter, international prospective registry to compare presentation and outcomes in PA patients treated with surgery or medical management alone. Methods A centralized database captured demographics, comorbidities, clinical presentation, visual findings, hormonal status, and imaging features at admission. Treatment was determined independently by each site. Key outcomes included visual, oculomotor, and hormonal recovery, complications, and hospital length of stay. Outcomes were also compared based on time from symptom onset to surgery, and from admission or transfer to the treating center. Statistical testing compared treatment groups based on 2-sided hypotheses and P less than.05. Results A total of 100 consecutive PA patients from 12 hospitals were enrolled, and 97 (67 surgical and 30 medical) were evaluable. Demographics, clinical features, presenting symptoms, hormonal deficits, and imaging findings were similar between groups. Severe temporal visual field deficit was more common in surgical patients. At 3 and 6 months, hormonal, visual, and oculomotor outcomes were similar. Stratifying based on severity of visual fields demonstrated no difference in any outcome at 3 months. Timing of surgery did not affect outcomes. Conclusion We found that medical and surgical management of PA yield similar 3-month outcomes. Although patients undergoing surgery had more severe visual field deficits, we could not clearly demonstrate that surgery led to better outcomes. Even without surgery, apoplectic tumor volumes regress substantially within 2 to 3 months, indicating that surgery is not always needed to reduce mass effect. [ABSTRACT FROM AUTHOR]

Importance: Benchmarks aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery (TS) are not available. Objective: We aimed to establish standardized outcome benchmarks for TS of pituitary adenomas. Design: A total of 2685 transsphenoidal tumor resections from 9 expert centers in 3 continents were analyzed. Setting: Patients were risk stratified, and the median values of each center's outcomes were established. The benchmark was defined as the 75th percentile of all median values for a particular outcome. The postoperative benchmark outcomes included surgical factors, endocrinologyspecific values, and neurology-specific values. Results: Of 2685 patients, 1149 (42.8%) defined the low-risk benchmark cohort. Within these benchmark cases, 831 (72.3%) patients underwent microscopic TS, and 308 (26.8%) patients underwent endoscopic endonasal resection. Of all tumors, 799 (29.8%) cases invaded the cavernous sinus. The postoperative complication rate was 19.6% with mortality between 0.0% and 0.8%. Benchmark cutoffs were ≤2.9% for reoperation rate, ≤1.9% for cerebrospinal fluid leak requiring intervention, and ≤15.5% for transient diabetes insipidus. At 6 months, benchmark cutoffs were calculated as follows: readmission rate: ≤6.9%, new hypopituitarism ≤6.0%, and tumor remnant ≤19.2%. Conclusions: This analysis defines benchmark values for TS targeting morbidity and mortality and represents the best outcomes in the best patients in expert centers. These cutoffs can be used to assess different centers, patient populations, and novel surgical techniques. It should be noted that the benchmark values may influence each other and must be evaluated in their own context. [ABSTRACT FROM AUTHOR]

Motivation Recombinant protein production is a widely used technique in the biotechnology and biomedical industries, yet only a quarter of target proteins are soluble and can therefore be purified. Results We have discovered that global structural flexibility, which can be modeled by normalized B -factors, accurately predicts the solubility of 12 216 recombinant proteins expressed in Escherichia coli. We have optimized these B -factors, and derived a new set of values for solubility scoring that further improves prediction accuracy. We call this new predictor the 'Solubility-Weighted Index' (SWI). Importantly, SWI outperforms many existing protein solubility prediction tools. Furthermore, we have developed 'SoDoPE' (Soluble Domain for Protein Expression), a web interface that allows users to choose a protein region of interest for predicting and maximizing both protein expression and solubility. Availability and implementation The SoDoPE web server and source code are freely available at https://tisigner.com/sodope and https://github.com/Gardner-BinfLab/TISIGNER-ReactJS , respectively. The code and data for reproducing our analysis can be found at https://github.com/Gardner-BinfLab/SoDoPE%5fpaper%5f2020. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Variants within the non-coding genome are frequently associated with phenotypes in genome-wide association studies. These non-coding regions may be involved in the regulation of gene expression, encode functional non-coding RNAs, or influence splicing and other cellular functions. We have curated a list of characterized non-coding human genome variants based on the published evidence that indicates phenotypic consequences of the variation. In order to minimize annotation errors, two curators have independently verified the supporting evidence for pathogenicity of each non-coding variant in the published literature. The database consists of 721 non-coding variants linked to the published literature describing the evidence of functional consequences. We have also sampled 7228 covariate-matched benign controls, that have a population frequency of over 5%, from the single nucleotide polymorphism database (dbSNP151) database. These were sampled controlling for potential confounding factors such as linkage with pathogenic variants, annotation type (untranslated region, intron, intergenic, etc.) and variant type (substitution or indel). The dataset presented here represents a curated repository, with a potential use for the training or evaluation of algorithms used in the prediction of non-coding variant functionality. Database URL : https://github.com/Gardner-BinfLab/ncVarDB. [ABSTRACT FROM AUTHOR]

Mammalian diversification has coincided with a rapid proliferation of various types of noncoding RNAs, including members of both snRNAs and snoRNAs. The significance of this expansion however remains obscure. While some ncRNA copy-number expansions have been linked to functionally tractable effects, such events may equally likely be neutral, perhaps as a result of random retrotransposition. Hindering progress in our understanding of such observations is the difficulty in establishing function for the diverse features that have been identified in our own genome. Projects such as ENCODE and FANTOM have revealed a hidden world of genomic expression patterns, as well as a host of other potential indicators of biological function. However, such projects have been criticized, particularly from practitioners in the field of molecular evolution, where many suspect these data provide limited insight into biological function. The molecular evolution community has largely taken a skeptical view, thus it is important to establish tests of function. We use a range of data, including data drawn from ENCODE and FANTOM, to examine the case for function for the recent copy number expansion inmammals of six evolutionarily ancient RNA families involved in splicing and rRNA maturation. We use several criteria to assess evidence for function: conservation of sequence and structure, genomic synteny, evidence for transposition, and evidence for species-specific expression. Applying these criteria, we find that only aminority of loci show strong evidence for function and that, for the majority, we cannot reject the null hypothesis of no function. [ABSTRACT FROM AUTHOR]

Motivation: The aim of this study is to assess the performance of RNA-RNA interaction prediction tools for all domains of life. Results: Minimum free energy (MFE) and alignment methods constitute most of the current RNA interaction prediction algorithms. The MFE tools that include accessibility (i.e. RNAup, IntaRNA and RNAplex) to the final predicted binding energy have better true positive rates (TPRs) with a high positive predictive values (PPVs) in all datasets than other methods. They can also differentiate almost half of the native interactions from background. The algorithms that include effects of internal binding energies to their model and alignment methods seem to have high TPR but relatively low associated PPV compared to accessibility based methods. Availability and Implementation: We shared our wrapper scripts and datasets at Github (github.- com/UCanCompBio/RNA_Interactions_Benchmark). All parameters are documented for personal use. [ABSTRACT FROM AUTHOR]

Motivation: Next generation sequencing technologies have provided us with a wealth of information on genetic variation, but predicting the functional significance of this variation is a difficult task. While many comparative genomics studies have focused on gene flux and large scale changes, relatively little attention has been paid to quantifying the effects of single nucleotide polymorphisms and indels on protein function, particularly in bacterial genomics. Results: We present a hidden Markov model based approach we call delta-bitscore (DBS) for identifying orthologous proteins that have diverged at the amino acid sequence level in a way that is likely to impact biological function. We benchmark this approach with several widely used datasets and apply it to a proof-of-concept study of orthologous proteomes in an investigation of host adaptation in Salmonella enterica. We highlight the value of the method in identifying functional divergence of genes, and suggest that this tool may be a better approach than the commonly used dN/dS metric for identifying functionally significant genetic changes occurring in recently diverged organisms. [ABSTRACT FROM AUTHOR]

Background Skull base tumors comprise many common benign brain tumors. Treatment has advanced, allowing many survivors to return to work. However, literature is limited about the neuropsychological status of these patients prior to treatment. Literature pertaining to the relationship between neuropsychological functioning and occupational ability prior to surgical intervention is even more limited. The purpose of this analysis was to evaluate the impact of neuropsychological function on work productivity in persons with skull base tumors prior to resection. Methods Neuropsychological function and work productivity were assessed in adults newly diagnosed with skull base tumors (n = 45) prior to surgical intervention. Univariate analyses identified potential predictors of work limitations; variables with P < .10 were analyzed using multivariate regression analyses controlled for age, sex, tumor type, and education. Results Poorer mental attention and flexibility (MF) and higher depressive symptoms (DS) were significantly associated with poor time management at work (MF: β = -0.59, P = .01; DS: β = 3.42, P < .01; R2 = 0.54). Difficulty meeting physical work demands was significantly associated with poorer visuospatial ability (VA) and higher depressive symptoms (VA: β = −3.30, P = .05; DS: β = 2.29, P < .01; R2 = 0.29). Lower learning and memory scores (LM) and higher depressive symptoms were significantly associated with difficulty meeting mental-interpersonal work demands (LM: β = −3.39, P = .04; DS: β = 3.25, P < .01; R2 = 0.47) and overall health-related loss of work productivity (LM: β = −0.72, P = .05; DS: β = 0.659, P < .001; R2 = 0.43). Conclusion Domains of neuropsychological function that predicted work productivity were identified. Future research should examine neuropsychological function, depressive symptoms, and work productivity across the care trajectory from diagnosis through long-term survivorship. [ABSTRACT FROM PUBLISHER]

Background The giant squid (Architeuthis dux ; Steenstrup, 1857) is an enigmatic giant mollusc with a circumglobal distribution in the deep ocean, except in the high Arctic and Antarctic waters. The elusiveness of the species makes it difficult to study. Thus, having a genome assembled for this deep-sea–dwelling species will allow several pending evolutionary questions to be unlocked. Findings We present a draft genome assembly that includes 200 Gb of Illumina reads, 4 Gb of Moleculo synthetic long reads, and 108 Gb of Chicago libraries, with a final size matching the estimated genome size of 2.7 Gb, and a scaffold N50 of 4.8 Mb. We also present an alternative assembly including 27 Gb raw reads generated using the Pacific Biosciences platform. In addition, we sequenced the proteome of the same individual and RNA from 3 different tissue types from 3 other species of squid (Onychoteuthis banksii, Dosidicus gigas , and Sthenoteuthis oualaniensis) to assist genome annotation. We annotated 33,406 protein-coding genes supported by evidence, and the genome completeness estimated by BUSCO reached 92%. Repetitive regions cover 49.17% of the genome. Conclusions This annotated draft genome of A. dux provides a critical resource to investigate the unique traits of this species, including its gigantism and key adaptations to deep-sea environments. [ABSTRACT FROM AUTHOR]

The article looks at a study which demonstrate superiority of robotic-assisted laparoscopic prostatectomy (RALP) when compared with conventional retropubic radical prostatectomy (RRP) in the maintaining of pre-surgery levels of sexual functioning. It mentions erectile dysfunction is a common side effect of prostatectomy in the treatment of prostate cancer. It conclude no significant effect on important sexual quality of life outcomes associated with the technique.