bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring chromatin conformation and gene co-expression through graph embedding
Authors: Varrone Marco , Nanni Luca , Ciriello Giovanni , Ceri Stefano 
Published: October 2020

Abstract

Motivation
The relationship between gene co-expression and chromatin conformation is of great biological interest. Thanks to high-throughput chromosome conformation capture technologies (Hi-C), researchers are gaining insights on the tri-dimensional organization of the genome. Given the high complexity of Hi-C data and the difficult definition of gene co-expression networks, the development of proper computational tools to investigate such relationship is rapidly gaining the interest of researchers. One of the most fascinating questions in this context is how chromatin topology correlates with gene co-expression and which physical interaction patterns are most predictive of co-expression relationships.

Results
To address these questions, we developed a computational framework for the prediction of co-expression networks from chromatin conformation data. We first define a gene chromatin interaction network where each gene is associated to its physical interaction profile; then, we apply two graph embedding techniques to extract a low-dimensional vector representation of each gene from the interaction network; finally, we train a classifier on gene embedding pairs to predict if they are co-expressed. Both graph embedding techniques outperform previous methods based on manually designed topological features, highlighting the need for more advanced strategies to encode chromatin information. We also establish that the most recent technique, based on random walks, is superior. Overall, our results demonstrate that chromatin conformation and gene regulation share a non-linear relationship and that gene topological embeddings encode relevant information, which could be used also for downstream analysis.

Availability and implementation
The source code for the analysis is available at: https://github.com/marcovarrone/gene-expression-chromatin.

Supplementary information
Supplementary data are available at Bioinformatics online.
amPEPpy 1.0: a portable and accurate antimicrobial peptide prediction tool
Authors: Lawrence Travis J , Carper Dana L , Spangler Margaret K , Carrell Alyssa A , Rush Tomás A , Minter Stephen J , Weston David J , Labbé Jessy L 
Published: October 2020

Abstract

Summary
Antimicrobial peptides (AMPs) are promising alternative antimicrobial agents. Currently, however, portable, user-friendly and efficient methods for predicting AMP sequences from genome-scale data are not readily available. Here we present amPEPpy, an open-source, multi-threaded command-line application for predicting AMP sequences using a random forest classifier.

Availability and implementation
amPEPpy is implemented in Python 3 and is freely available through GitHub (https://github.com/tlawrence3/amPEPpy).

Supplementary information
Supplementary data are available at Bioinformatics online.
Finding the fixed points of a Boolean network from a positive feedback vertex set
Authors: Aracena Julio , Cabrera-Crot Luis , Salinas Lilian 
Published: October 2020

AbstractMotivationIn the modeling of biological systems by Boolean networks, a key problem is finding the set of fixed points of a given network. Some constructed algorithms consider certain structural properties of the regulatory graph like those proposed by Akutsu et al. and Zhang et al., which consider a feedback vertex set of the graph. However, these methods do not take into account the type of action (activation and inhibition) between its components.ResultsIn this article, we propose a new algorithm for finding the set of fixed points of a Boolean network, based on a positive feedback vertex set P of its regulatory graph and which works, by applying a sequential update schedule, in time O(2|P|·n2+k), where n is the number of components and the regulatory functions of the network can be evaluated in time O(nk), k≥0. The theoretical foundation of this algorithm is due a nice characterization, that we give, of the dynamical behavior of the Boolean networks without positive cycles and with a fixed point.Availability and implementationAn executable file of FixedPoint algorithm made in Java and some examples of input files are available at: www.inf.udec.cl/˜lilian/FPCollector/.Supplementary informationSupplementary material is available at Bioinformatics online.
Machine phenotyping of cluster headache and its response to verapamil
Authors: Tso Amy R , Brudfors Mikael , Danno Daisuke , Grangeon Lou , Cheema Sanjay , Matharu Manjit , Nachev Parashkev 
Published: October 2020

Abstract
Cluster headache is characterized by recurrent, unilateral attacks of excruciating pain associated with ipsilateral cranial autonomic symptoms. Although a wide array of clinical, anatomical, physiological, and genetic data have informed multiple theories about the underlying pathophysiology, the lack of a comprehensive mechanistic understanding has inhibited, on the one hand, the development of new treatments and, on the other, the identification of features predictive of response to established ones. The first-line drug, verapamil, is found to be effective in only half of all patients, and after several weeks of dose escalation, rendering therapeutic selection both uncertain and slow. Here we use high-dimensional modelling of routinely acquired phenotypic and MRI data to quantify the predictability of verapamil responsiveness and to illuminate its neural dependants, across a cohort of 708 patients evaluated for cluster headache at the National Hospital for Neurology and Neurosurgery between 2007 and 2017. We derive a succinct latent representation of cluster headache from non-linear dimensionality reduction of structured clinical features, revealing novel phenotypic clusters. In a subset of patients, we show that individually predictive models based on gradient boosting machines can predict verapamil responsiveness from clinical (410 patients) and imaging (194 patients) features. Models combining clinical and imaging data establish the first benchmark for predicting verapamil responsiveness, with an area under the receiver operating characteristic curve of 0.689 on cross-validation (95% confidence interval: 0.651 to 0.710) and 0.621 on held-out data. In the imaged patients, voxel-based morphometry revealed a grey matter cluster in lobule VI of the cerebellum (−4, −66, −20) exhibiting enhanced grey matter concentrations in verapamil non-responders compared with responders (familywise error-corrected P = 0.008, 29 voxels). We propose a mechanism for the therapeutic effect of verapamil that draws on the neuroanatomy and neurochemistry of the identified region. Our results reveal previously unrecognized high-dimensional structure within the phenotypic landscape of cluster headache that enables prediction of treatment response with modest fidelity. An analogous approach applied to larger, globally representative datasets could facilitate data-driven redefinition of diagnostic criteria and stronger, more generalizable predictive models of treatment responsiveness.
Establishing two principal dimensions of cognitive variation in logopenic progressive aphasia
Authors: Ramanan Siddharth , Roquet Daniel , Goldberg Zoë-lee , Hodges John R , Piguet Olivier , Irish Muireann , Lambon Ralph Matthew A 
Published: October 2020

Abstract
Logopenic progressive aphasia (LPA) is a neurodegenerative syndrome characterised by sentence repetition and naming difficulties arising from left-lateralised temporoparietal atrophy. Clinical descriptions of LPA largely concentrate on profiling language deficits, however, accumulating evidence points to the presence of cognitive deficits even on tasks with minimal language demands. Although non-linguistic cognitive deficits in LPA are thought to scale with disease severity, patients at discrete stages of language dysfunction display overlapping cognitive profiles, suggesting individual-level variation in cognitive performance, independent of primary language dysfunction. To address this issue, we used principal component analysis to decompose individual-level variation in cognitive performance in 43 well-characterised LPA patients who underwent multi-domain neuropsychological assessments and structural neuroimaging. The principal component analysis solution revealed the presence of two, statistically independent factors, providing stable and clinically intuitive explanations for the majority of variance in cognitive performance in the syndrome. Factor 1 reflected ‘speech production and verbal memory’ deficits which typify LPA. Systematic variations were also confirmed on a second, orthogonal factor mainly comprising visuospatial and executive processes. Adopting a case-comparison approach, we further demonstrate that pairs of patients with comparable Factor 1 scores, regardless of their severity, diverge considerably on visuo-executive test performance, underscoring the inter-individual variability in cognitive profiles in comparably ‘logopenic’ patients. Whole-brain voxel-based morphometry analyses revealed that speech production and verbal memory factor scores correlated with left middle frontal gyrus, while visuospatial and executive factor scores were associated with grey matter intensity of right-lateralised temporoparietal, middle frontal regions and their underlying white matter connectivity. Importantly, LPA patients with poorer visuospatial and executive factor scores demonstrated greater right-lateralised temporoparietal and frontal atrophy. Our findings demonstrate the inherent variation in cognitive performance at an individual- and group-level in LPA, suggesting the presence of a genuine co-occurring cognitive impairment that is statistically independent of language function and disease severity.
Isolation and culture of functional adult human neurons from neurosurgical brain specimens
Authors: Park Thomas I-H , Schweder Patrick , Lee Kevin , Dieriks Birger V , Jung Yewon , Smyth Leon , Rustenhoven Justin , Mee Edward , Heppner Peter , Turner Clinton , Curtis Maurice A , Faull Richard L M , Montgomery Johanna M , Dragunow Michael 
Published: October 2020

AbstractThe ability to characterize and study primary neurons isolated directly from the adult human brain would greatly advance neuroscience research. However, significant challenges such as accessibility of human brain tissue and the lack of a robust neuronal cell culture protocol have hampered its progress. Here, we describe a simple and reproducible method for the isolation and culture of functional adult human neurons from neurosurgical brain specimens. In vitro, adult human neurons form a dense network and express a plethora of mature neuronal and synaptic markers. Most importantly, for the first time, we demonstrate the re-establishment of mature neurophysiological properties in vitro, such as repetitive fast-spiking action potentials, and spontaneous and evoked synaptic activity. Together, our dissociated and slice culture systems enable studies of adult human neurophysiology and gene expression under normal and pathological conditions and provide a high-throughput platform for drug testing on brain cells directly isolated from the adult human brain.
Understanding the biological basis of dyslexia at a neural systems level
Authors: Al Dahhan Noor Z , Kirby John R , Brien Donald C , Gupta Rina , Harrison Allyson , Munoz Douglas P 
Published: October 2020

Abstract
We examined the naming speed performance of 18 typically achieving and 16 dyslexic adults while simultaneously recording eye movements, articulations and fMRI data. Naming speed tasks, which require participants to name a list of letters or objects, have been proposed as a proxy for reading and are thought to recruit similar reading networks in the left hemisphere of the brain as more complex reading tasks. We employed letter and object naming speed tasks, with task manipulations to make the stimuli more or less phonologically and/or visually similar. Compared to typically achieving readers, readers with dyslexia had a poorer behavioural naming speed task performance, longer fixation durations, more regressions and increased activation in areas of the reading network in the left-hemisphere. Whereas increased network activation was positively associated with performance in dyslexics, it was negatively related to performance in typically achieving readers. Readers with dyslexia had greater bilateral activation and recruited additional regions involved with memory, namely the amygdala and hippocampus; in contrast, the typically achieving readers additionally activated the dorsolateral prefrontal cortex. Areas within the reading network were differentially activated by stimulus manipulations to the naming speed tasks. There was less efficient naming speed behavioural performance, longer fixation durations, more regressions and increased neural activity when letter stimuli were both phonologically and visually similar. Discussion focuses on the differences in activation within the reading network, how they are related to behavioural task differences, and how progress in furthering the understanding of the relationship between behavioural performance and brain activity can change the overall trajectories of children with reading difficulties by contributing to both early identification and remediation processes.
Severe Acute Respiratory Syndrome Coronavirus 2 Surveillance and Exposure in the Perioperative Setting With Universal Testing and Personal Protective Equipment Policies
Authors: Aslam Anoshe , Singh Jessica , Robilotti Elizabeth , Chow Karin , Bist Tarun , Reidy-Lagunes Diane , Shah Monika , Korenstein Deborah , Babady N Esther , Kamboj Mini 
Published: October 2020

Abstract

Background
New York City (NYC) experienced a surge of coronavirus disease 2019 (COVID-19) cases in March and April 2020. Since then, universal polymerase chain reaction (PCR)–based surveillance testing and personal protective equipment (PPE) measures are in wide use in procedural settings. There is limited published experience on the utility and sustainability of PCR-based surveillance testing in areas with receding and consistently low community COVID-19 rates.

Methods
The study was conducted at a tertiary care cancer center in NYC from 22 March to 22 August 2020. Asymptomatic patients underwent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing before surgeries, interventional radiology procedures, and endoscopy. Contact tracing in procedural areas was done if a patient with an initial negative screen retested positive within 48 hours of the procedure.

Results
From March 22 until August 22, 2020, 11 540 unique patients underwent 14 233 tests before surgeries or procedures at Memorial Sloan Kettering Cancer Center. Overall, 65 patients were positive, with a peak rate of 4.3% that fell below 0.3% after April 2020. Among the 65 positive cases, 3 were presymptomatic and 38 were asymptomatic. Among asymptomatic test-positive patients, 76% had PCR cycle threshold &gt;30 at first detection. Five patients tested newly positive in the immediate postoperative period, exposing 82 employees with 1 case of probable transmission (1.2%).

Conclusions
The prevalence of SARS-CoV-2 infection identified on preprocedural surveillance was low in our study, which was conducted in an area with limited community spread at the later stage of the study. Universal PPE is protective in procedural settings. Optimal and flexible diagnostic strategies are needed to accomplish and sustain the goals of comprehensive preprocedure surveillance testing.
Digital Wellbeing as a Dynamic Construct
Authors: Vanden Abeele Mariek M P 
Published: October 2020

AbstractMobile media support our autonomy by connecting us to persons, content and services independently of time and place constraints. At the same time, they challenge our autonomy: We face new struggles, decisions, and pressure in relation to whether, when and where we connect and disconnect. Digital wellbeing is a new concept that refers to the (lack) of balance that we may experience in relation to mobile connectivity. This article develops a theoretical model of digital wellbeing that accounts for the dynamic and complex nature of our relationship to mobile connectivity, thereby overcoming conceptual and methodological limitations associated with existing approaches. This model considers digital wellbeing an experiential state of optimal balance between connectivity and disconnectivity that is contingent upon a constellation of person-, device- and context-specific factors. I argue that these constellations represent pathways to digital wellbeing that—when repeated—affect wellbeing outcomes, and that the effectiveness of digital wellbeing interventions depends on their disruptive impact on these pathways.
Very late stent expansion with intracoronary lithotripsy: a case report
Authors: Demarchi Andrea , Ugo Fabrizio , Cavallino Chiara , Rametta Francesco 
Published: October 2020

Abstract

Background
Underexpanded stent in heavily calcified coronary lesion is common and persists over years. It is related to long-term failure and negative outcomes. Treatment of this situation after many years with intracoronary lithotripsy (ICL-Shockwave®) could be an option.

Case summary
We report a case of a man with underexpanded coronary stent implanted 11 years earlier. Optical coherence tomography highlighted the mechanism of stent underexpansion showing the presence of calcium stones under the old struts. Intracoronary lithotripsy crushed calcium under the stent struts causing its geometric change (from elliptical to round shape) and a consequent better transmission of the true radial force of the old stent.

Discussion
Heavily calcified coronary lesions lead to stent underexpansion which persists over years. Intracoronary lithotripsy could be a very late option to manage this unfavourable common result.
Is the EuroSCORE II reliable in surgical mitral valve repair? A single-centre validation study
Authors: Carino Davide , Denti Paolo , Ascione Guido , Del Forno Benedetto , Lapenna Elisabetta , Ruggeri Stefania , Agricola Eustachio , Buzzatti Nicola , Verzini Alessandro , Meneghin Roberta , Scandroglio Anna Mara , Monaco Fabrizio , Castiglioni Alessandro , Alfieri Ottavio , De Bonis Michele 
Published: October 2020

Abstract

OBJECTIVES
The EuroSCORE II is widely used to predict 30-day mortality in patients undergoing open and transcatheter cardiac surgery. The aim of this study is to evaluate the discriminatory ability of the EuroSCORE II in predicting 30-day mortality in a large cohort of patients undergoing surgical mitral valve repair in a high-volume centre.

METHODS
A retrospective review of our institutional database was carried on to find all patients who underwent mitral valve repair in our department from January 2012 to December 2019. Discrimination of the EuroSCORE II was assessed using receiver operating characteristic curves. The maximum Youden’s Index was employed to define the optimal cut-point. Calibration was assessed by generating calibration plot that visually compares the predicted mortality with the observed mortality. Calibration was also tested with the Hosmer–Lemeshow goodness-of-fit test. Finally, the accuracy of the models was tested calculating the Brier score.

RESULTS
A total of 2645 patients were identified, and the median EuroSCORE II was 1.3% (0.6–2.0%). In patients with degenerative mitral regurgitation (MR), the EuroSCORE II showed low discrimination (area under the curve 0.68), low accuracy (Brier score 0.27) and low calibration with overestimation of the 30-day mortality. In patients with secondary MR, the EuroSCORE II showed a good overall performance estimating the 30-day mortality with good discrimination (area under the curve 0.88), good accuracy (Brier score 0.003) and good calibration.

CONCLUSIONS
In patients with degenerative MR operated on in a high-volume centre with a high level of expertise in mitral valve repair, the EuroSCORE II significantly overestimates the 30-day mortality.
Upgrade from implantable cardioverter-defibrillator vs. de novo implantation of cardiac resynchronization therapy: long-term outcomes
Authors: Jędrzejczyk-Patej Ewa , Mazurek Michał , Kotalczyk Agnieszka , Kowalska Wiktoria , Konieczny-Kozielska Aleksandra , Kozielski Jonasz , Podolecki Tomasz , Szulik Mariola , Sokal Adam , Kowalski Oskar , Kalarus Zbigniew , Średniawa Beata , Lenarczyk Radosław 
Published: October 2020

Abstract

Aims
To assess and compare long-term mortality and predictors thereof in de novo cardiac resynchronization therapy defibrillators (CRT-D) vs. upgrade from an implantable cardioverter-defibrillator (ICD) to CRT-D.

Methods and results
Study population consisted of 595 consecutive patients with CRT-D implanted between 2002 and 2015 in a tertiary care, university hospital, in a densely inhabited, urban region of Poland [480 subjects (84.3%) with CRT-D de novo implantation; 115 patients (15.7%) upgraded from ICD to CRT-D]. In a median observation of 1692 days (range 457–3067), all-cause mortality for de novo CRT-D vs. CRT-D upgrade was 35.5% vs. 43.5%, respectively (P = 0.045). On multivariable regression analysis including all CRT recipients, the previously implanted ICD was an independent predictor for death [hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.10–2.29, P = 0.02]. For those, who were upgraded from ICD to CRT-D, the independent predictors for all-cause death were as follows: creatinine level (HR 1.01, 95% CI 1.00–1.02, P = 0.01), left ventricular end-systolic diameter (HR 1.07, 95% CI 1.02–1.11, P = 0.002), New York Heart Association (NYHA) IV class at baseline (HR 2.36, 95% CI 1.00–5.53, P = 0.049) and cardiac device-related infective endocarditis during follow-up (HR 2.42, 95% CI 1.02–5.75, P = 0.046). A new CRT scale (Creatinine ≥150 μmol/L; Remodelling, left ventricular end-systolic ≥59 mm; Threshold for NYHA, NYHA = IV) showed high prediction for mortality in CRT-D upgrades (AUC 0.70, 95% CI 0.59–0.80, P = 0.0007).

Conclusion
All-cause mortality in patients upgraded from ICD is significantly higher compared with de novo CRT-D implantations and reaches almost 45% within 4.5 years. A new CRT scale (Creatinine; Remodelling; Threshold for NYHA) has been proposed to help survival prediction following CRT upgrade.
Hepatomegaly and short stature in a 14-year-old with type 1 diabetes mellitus: case report
Authors: Fox Miriam T , Tamaroff Jaclyn , Percy Andrew G , Baker Stephanie , Altshuler Courtney , Baluyot Mariju , Stewart Rosalyn W 
Published: October 2020

Abstract

Background
Mauriac syndrome is a rare consequence of poorly controlled insulin-dependent diabetes, characterized by hepatomegaly, growth failure, delayed onset of puberty, and cushingoid features. Case reports of patients with Mauriac syndrome are found infrequently in the literature given historic improvements in diabetes management due to readily available insulin therapy.

Methods
We describe a case of a 14-year-old girl who presented with acute onset abdominal pain, distention, and orthopnea.

Results
She had a history of poorly controlled insulin-dependent diabetes as well as short stature. Abdominal imaging revealed impressive hepatomegaly. Laboratory testing showed markedly elevated triglycerides and cholesterol. Mauriac syndrome was suspected and diagnosed by liver biopsy, which demonstrated significant glycogenic hepatopathy.

Conclusions
This case provides an illustrative example of Mauriac syndrome in a child who did not experience delayed onset of puberty and continued to have regular menses unlike what has been previously described. Furthermore, this case highlights the important consideration for significant dyslipidemia in patients with Mauriac syndrome and discusses the challenges of controlling insulin-dependent diabetes in the adolescent population.