bluuebunny/crossref_metadata_2025_split huggingface dataset:
The discovery potential of RNA processing profiles
Authors: Pagès Amadís , Dotu Ivan , Pallarès-Albanell Joan , Martí Eulàlia , Guigó Roderic , Eyras Eduardo 
Published: April 2016

AbstractSmall non-coding RNAs are highly abundant molecules that regulate essential cellular processes and are classified according to sequence and structure. Here we argue that read profiles from size-selected RNA sequencing capture the post-transcriptional processing specific to each RNA family, thereby providing functional information independently of sequence and structure. We developed SeRPeNT, the first unsupervised computational method that exploits reproducibility across replicates and uses dynamic time-warping and density-based clustering algorithms to identify, characterize and compare small non-coding RNAs (sncRNAs) by harnessing the power of read profiles. We applied SeRPeNT to: a) generate an extended human annotation with 671 new sncRNAs from known classes and 131 from new potential classes, b) show pervasive differential processing between cell compartments and c) predict new molecules with miRNA-like behaviour from snoRNA, tRNA and long non-coding RNA precursors, potentially dependent on the miRNA biogenesis pathway. Furthermore, we validated experimentally four predicted novel non-coding RNAs: a miRNA, a snoRNA-derived miRNA, a processed tRNA and a new uncharacterized sncRNA. SeRPeNT facilitates fast and accurate discovery and characterization of small non-coding RNAs at unprecedented scale. SeRPeNT code is available under the MIT license athttps://github.com/comprna/SeRPeNT.
Using Ordinary Differential Equations to Explore Cancer-Immune Dynamics and Tumor Dormancy
Authors: Wilkie Kathleen P. , Hahnfeldt Philip , Hlatky Lynn 
Published: April 2016

AbstractCancer is not solely a disease of the genome, but is a systemic disease that affects the host on many functional levels, including, and perhaps most notably, the function of the immune response, resulting in both tumor-promoting inflammation and tumor-inhibiting cytotoxic action. The dichotomous actions of the immune response induce significant variations in tumor growth dynamics that mathematical modeling can help to understand. Here we present a general method using ordinary differential equations (ODEs) to model and analyze cancer-immune interactions, and in particular, immune-induced tumor dormancy.
Toxicity Management in CAR T cell therapy for B-ALL: Mathematical modelling as a new avenue for improvement
Authors: Hanson Shalla , Grimes David Robert , Taylor-King Jake P. , Bauer Benedikt , Warman Pravnam I. , Frankenstein Ziv , Kaznatcheev Artem , Bonassar Michael J. , Cannataro Vincent L. , Motawe Zeinab Y. , Lima Ernesto A. B. F. , Kim Sungjune , Davila Marco L. , Araujo Arturo 
Published: April 2016

AbstractAdvances in genetic engineering have made it possible to reprogram individual immune cells to express receptors that recognise markers on tumour cell surfaces. The process of re-engineering T cell lymphocytes to expressChimeric Antigen Receptors(CARs), and then re-infusing the CAR-modified T cells into patients to treat various cancers is referred to as CAR T cell therapy. This therapy is being explored in clinical trials - most prominently for B Cell Acute Lymphoblastic Leukaemia (B-ALL), a common B cell malignancy, for which CAR T cell therapy has led to remission in up to 90% of patients. Despite this extraordinary response rate, however, potentially fatal inflammatory side effects occur in up to 10% of patients who have positive responses. Further, approximately 50% of patients who initially respond to the therapy relapse. Significant improvement is thus necessary before the therapy can be made widely available for use in the clinic.To inform future development, we develop a mathematical model to explore interactions between CAR T cells, inflammatory toxicity, and individual patients’ tumour burdensin silico. This paper outlines the underlying system of coupled ordinary differential equations designed based on well-known immunological principles and widely accepted views on the mechanism of toxicity development in CAR T cell therapy for B-ALL - and reportsin silicooutcomes in relationship to standard and recently conjectured predictors of toxicity in a heterogeneous, randomly generated patient population. Our initial results and analyses are consistent with and connect immunological mechanisms to the clinically observed, counterintuitive hypothesis that initial tumour burden is a stronger predictor of toxicity than is the dose of CAR T cells administered to patients.We outline how the mechanism of action in CAR T cell therapy can give rise to such non-standard trends in toxicity development, and demonstrate the utility of mathematical modelling in understanding the relationship between predictors of toxicity, mechanism of action, and patient outcomes.
The hippocampus generalizes across memories that share item and context information
Authors: Libby Laura A. , Ragland J. Daniel , Ranganath Charan 
Published: April 2016

ABSTRACTEpisodic memory is known to rely on the hippocampus, but how the hippocampus organizes different episodes to permit their subsequent retrieval remains controversial. According to one view, hippocampal coding differentiates between similar events to reduce interference, whereas an alternative view is that the hippocampus assigns similar representations to events that share item and context information. Here, we used multivariate analyses of activity patterns measured with functional magnetic resonance imaging (fMRI) to characterize how the hippocampus distinguishes between memories based on similarity of their item and/or context information. Hippocampal activity patterns discriminated between events that shared either item or context information, but generalized across events that shared similar item-context associations. The current findings provide novel evidence that, whereas the hippocampus can resist mnemonic interference by separating events that generalize along a single attribute dimension, overlapping hippocampal codes may support memory for events with overlapping item-context relations.
Diverticulitis: does age matter?
Authors: Horesh Nir , Shwaartz Chaya , Amiel Imri , Nevler Avinoam , Shabtai Esther , Lebedeyev Alexander , Nadler Roi , Rosin Danny , Gutman Mordechai , Zmora Oded 
Published: April 2016

AbstractObjectiveAcute diverticulitis has been traditionally associated with worse outcome in young patients, indicating a more aggressive surgical approach is required for them. The aim of this study was to assess whether acute diverticulitis was more virulent in young patients.MethodsA retrospective, cross‐sectional study included all patients who were admitted for a first episode of acute diverticulitis between January 2004 and December 2013. The patients were divided into two groups (≤50 years and >50 years) based on their age. Patients' characteristics, clinical and surgical data were recorded and analyzed.ResultsOverall, 636 patients were included in the database, including 177 (27.8%) in the younger group and 459 in the elder group. There were no significant differences between the groups in disease complexity, peritonitis, laboratory work‐up, vital signs on presentation, bowel obstruction or the presence of fistula and abscess in need of drainage. Younger patients had more free extra‐luminal air on computed tomography (CT) scan (P = 0.03). Surgical data, including the intra‐operative modified Hinchey score and the need for emergency and additional surgery did not significantly differ between the two groups. Young patients had more readmissions (P = 0.01) due to acute diverticulitis, diverticular complications and elective surgery. Length of hospital stay (P = 0.0001) was longer and postoperative complications were more common in the elder patients.ConclusionsThe clinical presentation of acute diverticulitis does not seem to be worse in the young population. Younger patients tend to have a more severe presentation on CT scan and more readmissions, but this did not translate to a more severe disease course.
Cyanoacrylate therapy for the treatment of gastric varices: a new method
Authors: Singh Virendra , Singh Ranjan , Bhalla Ashish , Sharma Navneet 
Published: April 2016

ObjectiveCyanoacrylate (CYA) injection is recommended for bleeding gastric varices (GV) but with significant adverse effects. Transesophageal endoscopic ultrasound‐guided therapy of large GV with a combined coil and CYA injection has shown promising results. However, it is expensive and requires technical expertise. In this study, we aimed to compare the safety and efficacy of a new method with UCYA [undiluated CYA (UCYA) followed by lipiodol‐diluated CYA (DCYA)] in the management of large bleeding GV.MethodsFifteen consecutive patients with bleeding from large GV (>1 cm) were prospectively treated with DCYA and another 15 patients treated with UCYA retrospectively. All patients in the DCYA group underwent thoracic computed tomography scan to identify glue embolism.ResultsBaseline characteristics were similar between the two groups. Rates of GV obliteration and rebleeding were 100% vs 93.3% (P = 0.309) and 6.7% vs 33.3% (P = 0.06) in the DCYA and UCYA groups, respectively. One patient in the UCYA group had needle fixation which led to fatal bleeding after forceful needle extraction. In DCYA group none had glue embolism.ConclusionsBoth UCYA and DCYA are effective in treating bleeding from large GV. DCYA has lower rebleeding rates and tends to have fewer adverse events than UCYA injection, although the differences are not statistically significant. Large‐sample‐sized prospective randomized trials are required.
A new integrative framework for large‐scale assessments of biodiversity and community dynamics, using littoral gastropods and crabs of British Columbia, Canada
Authors: Castelin M. , Van Steenkiste N. , Pante E. , Harbo R. , Lowe G. , Gilmore S. R. , Therriault T. W. , Abbott C. L. 
Published: April 2016

AbstractImproving our understanding of species responses to environmental changes is an important contribution ecologists can make to facilitate effective management decisions. Novel synthetic approaches to assessing biodiversity and ecosystem integrity are needed, ideally including all species living in a community and the dynamics defining their ecological relationships. Here, we present and apply an integrative approach that links high‐throughput, multicharacter taxonomy with community ecology. The overall purpose is to enable the coupling of biodiversity assessments with investigations into the nature of ecological interactions in a community‐level data set. We collected 1195 gastropods and crabs in British Columbia. First, the General mixed Yule‐coalescent (GMYC) and the Poisson Tree Processes (PTP) methods for proposing primary species‐hypotheses based on cox1 sequences were evaluated against an integrative taxonomic framework. We then used data on the geographic distribution of delineated species to test species co‐occurrence patterns for nonrandomness using community‐wide and pairwise approaches. Results showed that PTP generally outperformed GMYC and thus constitutes a more effective option for producing species‐hypotheses in community‐level data sets. Nonrandom species co‐occurrence patterns indicative of ecological relationships or habitat preferences were observed for grazer gastropods, whereas assemblages of carnivorous gastropods and crabs appeared influenced by random processes. Species‐pair associations were consistent with current ecological knowledge, thus suggesting that applying community assembly within a large taxonomical framework constitutes a valuable tool for assessing ecological interactions. Combining phylogenetic, morphological and co‐occurrence data enabled an integrated view of communities, providing both a conceptual and pragmatic framework for biodiversity assessments and investigations into community dynamics.
TEMPLE: analysing population genetic variation at transcription factor binding sites
Authors: Litovchenko Maria , Laurent Stefan 
Published: April 2016

AbstractGenetic variation occurring at the level of regulatory sequences can affect phenotypes and fitness in natural populations. This variation can be analysed in a population genetic framework to study how genetic drift and selection affect the evolution of these functional elements. However, doing this requires a good understanding of the location and nature of regulatory regions and has long been a major hurdle. The current proliferation of genomewide profiling experiments of transcription factor occupancies greatly improves our ability to identify genomic regions involved in specific DNA–protein interactions. Although software exists for predicting transcription factor binding sites (TFBS), and the effects of genetic variants on TFBS specificity, there are no tools currently available for inferring this information jointly with the genetic variation at TFBS in natural populations. We developed the software Transcription Elements Mapping at the Population LEvel (TEMPLE), which predicts TFBS, evaluates the effects of genetic variants on TFBS specificity and summarizes the genetic variation occurring at TFBS in intraspecific sequence alignments. We demonstrate that TEMPLE's TFBS prediction algorithms gives identical results to PATSER, a software distribution commonly used in the field. We also illustrate the unique features of TEMPLE by analysing TFBS diversity for the TF Senseless (SENS) in one ancestral and one cosmopolitan population of the fruit fly Drosophila melanogaster. TEMPLE can be used to localize TFBS that are characterized by strong genetic differentiation across natural populations. This will be particularly useful for studies aiming to identify adaptive mutations. TEMPLE is a java‐based cross‐platform software that easily maps the genetic diversity at predicted TFBSs using a graphical interface, or from the Unix command line.
The Immunogenicity of CRISP1 Plasmid‐Based Contraceptive Vaccine can be Improved When Using Chitosan Nanoparticles as the Carrier
Authors: Luo Jin , Liu Xue‐li , Zhang Yi , Wang Ya‐qin , Xu Wang‐ming , Yang Jing 
Published: April 2016

ProblemTo evaluate the effectiveness and security of a contraceptive vaccine using plasmid DNA encoding mouse CRISP1 as antigen and chitosan nanoparticles as the carrier.Method of studyChitosan‐pcDNA3.1‐mCRISP1 Nanoparticles (CS‐DNA NPs) were prepared and characterized in terms of morphology, zeta potential, polydispersity index, and binding capacity of pDNA. The cytotoxicity and gene transfer capability of CS‐DNA NPs were assessed in COS‐7 cells compared to Lipofectamine 2000™. Four groups of mice received three injections of 0.9% normal saline, pcDNA3.1 vector, pcDNA3.1‐CRISP1, or CS‐DNA NPs, respectively. ELISA was used to examine the immune responses. Fertility and mean litter size were analyzed by natural mating.ResultsCS‐DNA NPs have a spherical or elliptical shape with a mean diameter of 189.3 nm, positive zeta potential, and good DNA condensation. It also showed high DNAse resistance and good transfection efficiency without cell toxicity. The titers of anti‐mCRISP1 antibodies from CS‐DNA NP‐immunized mice were significantly higher than that of pcDNA3.1‐CRISP1 group. Male and female CS‐DNA NP‐immunized animals were recognized with a statistically significant reduction in their fertility compared with pcDNA3.1‐CRISP1‐immunized mice.ConclusionThis study demonstrated that using chitosan‐DNA nanoparticles as the carrier can improve the immunogenicity of mCRISP1 DNA contraceptive vaccine with good security.
The relation between executive functioning, reaction time, naming speed, and single word reading in children with typical development and language impairments
Authors: Messer David , Henry Lucy A. , Nash Gilly 
Published: April 2016

BackgroundFew investigations have examined the relationship between a comprehensive range of executive functioning (EF) abilities and reading.AimsOur investigation identified components of EF that independently predicted single word reading, and determined whether their predictive role remained when additional variables were included in the regression analyses. This provided information about the EF processes that are related to reading, and the unity and diversity of EF.SampleThis study consisted of 160 children: 88 were typically developing with no language difficulties; 72 had language impairments.MethodThe assessments involved decoding, 10 measures of EF, reaction time, naming speed, non‐verbal and verbal age‐equivalent scores.Results and conclusionsIn the first regression analysis, which only concerned the EF variables, the following verbal forms of EF had significant relationships with decoding: working memory, fluency, planning, and inhibition. Further regression analyses included additional predictor variables: reaction time, naming speed, and age‐equivalent scores. These analyses indicated that most of the EF variables continued to predict decoding even when entered with competitor variables. Furthermore, after the entry of EF variables, there were no group differences in decoding (typical vs. language difficulties). We discuss the contribution of EF and other variables to reading abilities.
Prevalence and prognosis of a low serum testosterone in men with type 2 diabetes: the Fremantle Diabetes Study Phase II
Authors: Hamilton Emma J. , Davis Wendy A. , Makepeace Ashley , Lim Ee Mun , Yeap Bu B. , Peters Kirsten E. , Davis Timothy M. E. 
Published: April 2016

SummaryBackgroundBecause published studies have usually involved imprecise assays and selected patients with limited additional data and follow‐up, the consequences of a low serum testosterone in diabetes are unclear. This study assessed the prevalence, associates and prognosis of a low testosterone in community‐dwelling men with type 2 diabetes.DesignLongitudinal observational study.Patients788 men (mean ± SD age: 65·8 ± 11·3 years) followed for 4·0 ± 1·1 years.MeasurementsSerum testosterone, SHBG, erectile dysfunction (ED; Sexual Health Inventory for Men score <22), anaemia (haemoglobin <130 g/l), all‐cause mortality.ResultsThe mean ± SD total serum testosterone by liquid chromatography/mass spectrometry was 13·1 ± 5·9 nmol/l (30·6% <10 nmol/l). Most men with a total testosterone <10 nmol/l (67·0%) had a normal/low serum LH. Serum testosterone was independently associated with anaemia (P < 0·001), but not ED (P = 0·80), in logistic regression models. The optimal cut‐point (Youden Index) for anaemia was 9·8 nmol/l (sensitivity 53·6%, specificity 75·4%). During the follow‐up, 102 men (12·9%) died. There was a U‐shaped relationship between total serum testosterone quintiles and death (P = 0·003, log rank test). The middle quintile (>11·1 to ≤13·7 nmol/l) had the lowest risk and there was a 78% increased risk for highest (>16·9 nmol/l) vs lowest (≤8·6 nmol/l) quintile in Cox proportional hazards modelling (P = 0·036). Free serum testosterone and SHBG quintiles were not associated with death.ConclusionsThese data provide some support for the general conventional serum testosterone <10 nmol/l cut‐point in identifying an increased risk of anaemia and the subsequent death in men with type 2 diabetes, but indicate that high‐normal levels are also an adverse prognostic indicator.
Thyroid lobectomy is an effective option for unilateral benign nodular disease
Authors: Lytrivi Maria , Kyrilli Aglaia , Burniat Agnès , Ruiz Patino Maria , Sokolow Youri , Corvilain Bernard 
Published: April 2016

SummaryObjectiveThe use of thyroid lobectomy in the treatment of unilateral, benign nodules is limited by the potential of nodular recurrence in the remaining lobe. This study aimed to assess the rate and clinical impact of nodular recurrence in the contralateral lobe after thyroid lobectomy and to identify predictive factors of recurrence.DesignSingle‐centre retrospective study.PatientsRecords of patients that underwent lobectomy for unilateral thyroid nodules between 1991 and 2010 were reviewed and 270 patients were included. Exclusion criteria were: presence of contralateral nodule(s) ≥5 mm on preoperative ultrasound, diagnosis of cancer necessitating completion thyroidectomy or pseudonodules. Recurrence was defined as the occurrence of nodule(s) ≥5 mm in the remaining lobe on at least one postoperative ultrasound. A set of clinical, imaging, histological and biochemical parameters was tested as predictors of recurrence using logistic regression.ResultsAfter a median follow‐up of 78 months (range, 12–277 months), the global recurrence rate was 42% and recurrence of nodules of a size ≥1 cm occurred in 19%. Reoperation rate was 1·1%. 90% of patients were treated postoperatively by levothyroxine. Median time to nodular recurrence was 4 years. Preoperative contralateral lobe volume and resected thyroid weight were identified as significant predictors of recurrence (P = 0·045 and P = 0·03 respectively).ConclusionsThyroid lobectomy is an effective therapeutic strategy for unilateral, benign nodules, resulting in a low rate of clinically relevant nodular relapse in a mildly iodine‐deficient area. Patients with uninodular disease and a contralateral lobe of normal size are particularly good candidates for lobectomy.
Neutral associations of testosterone, dihydrotestosterone and estradiol with fatal and non‐fatal cardiovascular events, and mortality in men aged 17–97 years
Authors: Chan Yi X. , Knuiman Matthew W. , Hung Joseph , Divitini Mark L. , Beilby John P. , Handelsman David J. , Beilin Jonathan , McQuillan Brendan , Yeap Bu B. 
Published: April 2016

SummaryContextLower testosterone (T) is associated with poorer health outcomes in older men, however, the relationship between T, dihydrotestosterone (DHT) and estradiol (E2) with cardiovascular disease (CVD) in younger to middle‐aged men remains unclear.ObjectivesWe assessed associations between endogenous sex hormones with mortality (all‐cause and CVD) and CVD events, in a cohort of men aged 17–97 years.Participants and methodsSex hormones were assayed using mass spectrometry in 2143 men from the 1994/5 Busselton Health Survey. Outcomes to December 2010 were analysed.ResultsOf the 1804 men included in the analysis, mean age was 50·3 ± 16·8 years and 68·9% of men were aged <60. Mean follow‐up period was 14·9 years. There were 319 deaths, 141 CVD deaths and 399 CVD events. Compared to the full cohort, men who died had lower baseline T (12·0 ± 4·4 vs 13·6 ± 4·9 nmol/l), free T (181·9 ± 52·9 vs 218·3 ± 63·8 pmol/l) and DHT (1·65 ± 0·64 vs 1·70 ± 0·72 nmol/l), but higher E2 (64·0 ± 32 vs 60·1 ± 30·2 pmol/l). After adjustment for risk factors, T was not associated with mortality (adjusted HR = 0·90, 95% CI 0·79–1·04; P = 0·164 for every increase in 1 SD of T), CVD deaths (adjusted HR = 1·04, 95% CI 0·84–1·29; P = 0·708) or CVD events (adjusted HR = 1·03, 95% CI 0·92–1·15, P = 0·661). No associations were found for free T, DHT or E2. Results were similar for men older and younger than 60 years.ConclusionsIn predominantly middle‐aged men, T, DHT and E2 do not influence mortality or CVD outcomes. This neutral association of hormones with CVD contrasts with prior studies of older men.