bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning techniques for detecting topological avatars of new physics
Authors: Bevan A. J. 
Published: November 2019

The search for highly ionizing particles in nuclear track detectors (NTDs) traditionally requires experts to manually search through samples in order to identify regions of interest that could be a hint of physics beyond the standard model of particle physics. The advent of automated image acquisition and modern data science, including machine learning-based processing of data presents an opportunity to accelerate the process of searching for anomalies in NTDs that could be a hint of a new physics avatar. The potential for modern data science applied to this topic in the context of the MoEDAL experiment at the large Hadron collider at the European Centre for Nuclear Research, CERN, is discussed.
This article is part of a discussion meeting issue ‘Topological avatars of new physics’.
Transcranial random noise stimulation for the acute treatment of depression: a randomized controlled trial
Authors: Nikolin Stevan , Alonzo Angelo , Martin Donel , Gálvez Veronica , Buten Sara , Taylor Rohan , Goldstein James , Oxley Cristal , Hadzi-Pavlovic Dusan , Loo Colleen K. 
Published: November 2019

AbstractBackgroundTranscranial electrical stimulation has broad potential as a treatment for depression. Transcranial random noise stimulation (tRNS), which delivers randomly fluctuating current intensities, may have greater cortical excitatory effects compared to other forms of transcranial electrical stimulation. We therefore aimed to investigate the antidepressant efficacy of tRNS.MethodsDepressed participants were randomly assigned by computer number generator to receive 20 sessions of either active or sham tRNS over four weeks in a double-blinded, parallel group randomized-controlled trial. tRNS was delivered for 30mins with a direct current offset of 2mA and a random noise range of 2mA. Primary analyses assessed changes in depression severity using the Montgomery-Asperg Depression Rating Scale (MADRS). Neuroplasticity, neuropsychological, and safety outcomes were analysed as secondary measures.Results69 participants were randomised, of which three discontinued treatment early leaving 66 (sham n = 34, active n = 32) for per-protocol analysis. Depression severity scores reduced in both groups (MADRS reduction in sham = 7.0 [95%CI 5.0-8.9]; and active = 5.2 [95%CI 3.2-7.3]). However, there were no differences between active and sham groups in the reduction of depressive symptoms, or the number of participants meeting response (sham = 14.7%; active = 3.1%) and remission criteria (sham = 5.9%; active = 0%). Erythema, paraesthesia, fatigue, and dizziness/light-headedness occurred more frequently in the active tRNS group. Neuroplasticity, neuropsychological and acute cognitive effects were comparable between groups.ConclusionOur results do not support the use of tRNS with the current stimulation parameters as a therapeutic intervention for the treatment of depression.Clinical trial registration at clinicaltrials.gov/NCT01792414.Significance StatementThis is the first randomized sham-controlled clinical trial of a four-week course of transcranial random noise stimulation (tRNS) for the treatment of depression. tRNS is a relatively novel form of non-invasive electrical stimulation that uses mild, randomly fluctuating currents to constrain homeostatic mechanisms and increase brain excitability. We investigated effects across multiple validated mood outcomes and comprehensively assessed cognitive, neurophysiological, and physical side effects to examine the safety of tRNS. We found no differences between active and sham conditions for all mood outcomes, and are thus unable to lend support for tRNS as an effective treatment for depression. We found tRNS to be well-tolerated with no adverse acute cognitive, neuropsychological or severe phyisical side effects, suggesting a course of 20 repeated sessions can be delivered safely.
Somatic evolution in non-neoplastic IBD-affected colon
Authors: Olafsson Sigurgeir , McIntyre Rebecca E. , Coorens Tim , Butler Timothy , Jung Hyunchul , Robinson Philip , Lee-Six Henry , Sanders Mathijs A. , Arestang Kenneth , Dawson Claire , Tripathi Monika , Strongili Konstantina , Hooks Yvette , Stratton Michael R. , Parkes Miles , Martincorena Inigo , Raine Tim , Campbell Peter J. , Anderson Carl A. 
Published: November 2019

Summary paragraphInflammatory bowel disease (IBD) is a chronic inflammatory disease associated with increased risk of gastrointestinal cancers. Here, we whole-genome sequenced 447 colonic crypts from 46 IBD patients, and compared these to 412 crypts from 41 non-IBD controls. The average mutation rate of affected colonic epithelial cells is 2.4-fold that of healthy colon and this increase is mostly driven by acceleration of mutational processes ubiquitously observed in normal colon. In contrast to the normal colon, where clonal expansions outside the confines of the crypt are rare, we observed widespread millimeter-scale clonal expansions. We discovered non-synonymous mutations inARID1A, FBXW7, PIGR and ZC3H12A,and genes in the interleukin 17 and Toll-like receptor pathways, under positive selection in IBD. These results suggest distinct selection mechanisms in the colitis-affected colon and that somatic mutations potentially play a causal role in IBD pathogenesis.
Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy inBRCA1/2-mutant metastatic breast cancer
Authors: Waks Adrienne G. , Cohen Ofir , Kochupurakkal Bose , Kim Dewey , Dunn Connor E. , Buendia Buendia Jorge , Wander Seth , Helvie Karla , Lloyd Maxwell R. , Marini Lori , Hughes Melissa E. , Freeman Samuel S. , Percy Ivy S. , Geradts Joseph , Isakoff Steve , LoRusso Patricia , Adalsteinsson Viktor A. , Tolaney Sara M. , Matulonis Ursula , Krop Ian E. , D’Andrea Alan D. , Winer Eric P. , Lin Nancy U. , Shapiro Geoffrey I. , Wagle Nikhil 
Published: November 2019

AbstractBackgroundLittle is known about mechanisms of resistance to PARP inhibitors and platinum chemotherapy in patients with metastatic breast cancer andBRCA1/2 mutations. Further investigation of resistance in clinical cohorts may point to strategies to prevent or overcome treatment failure.Patients and MethodsWe obtained tumor biopsies from metastatic breast cancer patients withBRCA1/2deficiency before and after acquired resistance to PARP inhibitor or platinum chemotherapy. Whole exome sequencing was performed on each tumor, germline DNA, and circulating tumor DNA. Tumors underwent RNA sequencing, and immunohistochemical staining for RAD51 foci on tumor sections was performed for functional assessment of intact homologous recombination.ResultsPre- and post-resistance tumor samples were sequenced from 8 patients (4 withBRCA1and 4 withBRCA2mutation; 4 treated with PARP inhibitor and 4 with platinum). Following disease progression on DNA-damaging therapy, four patients (50%) acquired at least one somatic reversion alteration likely to result in functional BRCA1/2 protein detected by tumor or circulating tumor DNA sequencing. Two patients with germlineBRCA1deficiency acquired genomic alterations anticipated to restore homologous recombination through increased DNA end resection: loss ofTP53BP1in one patient and amplification ofMRE11Ain another. RAD51 foci were acquired post-resistance in all patients with genomic reversion, consistent with reconstitution of homologous recombination. All patients whose tumors demonstrated RAD51 foci post-resistance were intrinsically resistant to subsequent lines of DNA-damaging therapy.ConclusionsGenomic reversion inBRCA1/2was the most commonly observed mechanism of resistance, occurring in 4 of 8 patients. Novel sequence alterations leading to increased DNA end resection were seen in two patients, and may be targetable for therapeutic benefit. The presence of RAD51 foci by immunohistochemistry was consistent with BRCA1/2 protein functional status from genomic data and predicted response to later DNA-damaging therapy, supporting RAD51 focus formation as a clinically useful biomarker.
A framework for closed-loop neurofeedback for real-time EEG decoding
Authors: Tuckute Greta , Hansen Sofie Therese , Kjaer Troels Wesenberg , Hansen Lars Kai 
Published: November 2019

AbstractNeurofeedback based on real-time brain imaging allows for targeted training of brain activity with demonstrated clinical applications. A rapid technical development of electroen-cephalography (EEG)-based systems and an increasing interest in cognitive training has lead to a call for accessible and adaptable software frameworks. Here, we present and outline the core components of a novel open-source neurofeedback framework based on scalp EEG signals for real-time neuroimaging, state classification and closed-loop feedback.The software framework includes real-time signal preprocessing, adaptive artifact rejection, and cognitive state classification from scalp EEG. The framework is implemented using exclusively Python source code to allow for diverse functionality, high modularity, and easy extendibility of software development depending on the experimenter’s needs.As a proof of concept, we demonstrate the functionality of our new software framework by implementing an attention training paradigm using a consumer-grade, dry-electrode EEG system. Twenty-two participants were trained on a single neurofeedback session with behavioral pre- and post-training sessions within three consecutive days. We demonstrate a mean decoding error rate of 34.3% (chance=50%) of subjective attentional states. Hence, cognitive states were decoded in real-time by continuously updating classification models on recently recorded EEG data without the need for any EEG recordings prior to the neurofeedback session.The proposed software framework allows a wide range of users to actively engage in the development of novel neurofeedback tools to accelerate improvements in neurofeedback as a translational and therapeutic tool.
Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages
Authors: Dupont Maeva , Souriant Shanti , Balboa Luciana , Vu Manh Thien-Phong , Pingris Karine , Rousset Stella , Cougoule Céline , Rombouts Yoann , Poincloux Renaud , Ben Neji Myriam , Allers Carolina , Kaushal Deepak , Kuroda Marcelo J. , Benet Susana , Martinez-Picado Javier , Izquierdo-Useros Nuria , del Carmen Sasiain Maria , Maridonneau-Parini Isabelle , Neyrolles Olivier , Vérollet Christel , Lugo-Villarino Geanncarlo 
Published: November 2019

AbstractWhile tuberculosis (TB) is a risk factor in HIV-1-infected individuals, the mechanisms by whichMycobacterium tuberculosisworsens HIV-1 pathogenesis remain poorly understood. Recently, we showed that HIV-1 infection and spread are exacerbated in macrophages exposed to TB-associated microenvironments due to tunneling nanotube (TNT) formation. To identify molecular factors associated with TNT function, we performed a transcriptomic analysis in these macrophages, and revealed the up-regulation of the lectin receptor Siglec-1. We demonstrate Siglec-1 expression depends on TB-mediated production of type I interferon. In co-infected non-human primates, Siglec-1 is highly expressed by alveolar macrophages, whose abundance correlates with pathology and activation of the type I interferon/STAT1 pathway. Intriguingly, Siglec-1 expression localizes exclusively on microtubule-containing TNT that are long and carry HIV-1 cargo. Siglec-1 depletion in macrophages decreases TNT length, diminishes HIV-1 capture and cell-to-cell transfer, and abrogates TB-driven exacerbation of HIV-1 infection. Altogether, we uncover a deleterious role for Siglec-1 in TB-HIV-1 co-infection, and its localization on TNT opens new avenues to understand cell-to-cell viral spread.
A systematic evaluation of Mycobacterium tuberculosis Genome-Scale Metabolic Networks
Authors: López-Agudelo Víctor A , Laing Emma , Mendum Tom A , Baena Andres , Barrera Luis F , Beste Dany JV , Rios-Estepa Rigoberto 
Published: November 2019

AbstractThe metabolism of the causative agent of TB, Mycobacterium tuberculosis (Mtb) has recently re-emerged as an attractive drug target. A powerful approach to study Mtb metabolism is to use a systems biology framework, such as a Genome-Scale Metabolic Network (GSMN) that allows the dynamic interactions of the many individual components of metabolism to be interrogated together. Several GSMNs networks have been constructed for Mtb and used to study the complex relationship between Mtb genotype and phenotype. However, their utility is hampered by the existence of multiple models of varying properties and performances. Here we systematically evaluate eight recently published metabolic models of Mtb-H37Rv to facilitate model choice. The best performing models, sMtb2018 and iEK1011, were refined and improved for use in future studies by the TB research community.
Invasive in the North: New latitudinal record for Argentine ants in Europe
Authors: Charrier N. Pierre , Hervet Caroline , Bonsergent Claire , Charrier Matthieu , Malandrin Laurence , Kaufmann Bernard , Gippet Jérôme M. W. 
Published: November 2019

AbstractEnvironmental niche models predict the presence of the invasive Argentine ant in north-western Europe, especially along all the French Atlantic coast. Yet, the species has never been observed North from the 45th parallel in Europe, suggesting either that current models are wrong or that Argentine ants are already spreading north inconspicuously. Here, we report a three-hectare wide colony of Argentine ants, detected in 2016 in Nantes, France, which is 300 km north of the former northern-most outdoor population of this species in Europe. COI sequencing revealed that the haplotype of this new colony is the same as the one found in the so-called Catalonian supercolony, which is distinct from the haplotype found over most of the species range in Europe. Our discovery confirms models’ predictions that Argentine ants can colonize north-western Europe and suggests that they might have already reached several other locations along the French Atlantic coast. Detection surveys should be conducted in order to assess Argentine ants’ invasion patterns in Western France, particularly in high introduction risk areas such as major cities and maritime ports.
Modulation of dopamine D1 receptors via histamine H3 receptors is a novel therapeutic target for Huntington’s disease
Authors: Moreno-Delgado David , Puigdellívol Mar , Moreno Estefanía , Rodríguez-Ruiz Mar , Botta Joaquín , Gasperini Paola , Chiarlone Anna , Howell Lesley A. , Scarselli Marco , Casadó Vicent , Cortés Antoni , Ferré Sergi , Guzmán Manuel , Lluís Carme , Alberch Jordi , Canela Enric , Ginés Sílvia , McCormick Peter J. 
Published: November 2019

AbstractEarly Huntington’s disease (HD) include over-activation of dopamine D1 receptors (D1R), producing an imbalance in dopaminergic neurotransmission and cell death. To reduce D1R over-activation, we present a strategy based on targeting complexes of D1R and histamine H3 receptors (H3R). Using an HD striatal cell model and HD organotypic brain slices we found that D1R-induced cell death signaling and neuronal degeneration, are mitigated by an H3R antagonist. We demonstrate that the D1R-H3R heteromer is expressed in HD animal models at early but not late stages of HD, correlating with HD progression. In accordance, we found this target expressed in human control subjects and low-grade HD patients. Finally, treatment of HD mice with an H3R antagonist prevented cognitive and motor learning deficits, as well as the loss of heteromer expression. Taken together, our results indicate that D1R - H3R heteromers play a pivotal role in dopamine signaling and represent novel targets for treating HD.Impact StatementProgression of Huntington’s disease can be slowed by altering dopamine signalling through the Dopamine 1 receptor - Histamine 3 receptor heteromer.
A Hierarchical Model of the Hypothalamo-Adreno-Pituitary system
Authors: La Rota Camilo , Tudor Vuza Dan , Climescu-Haulica Adriana 
Published: November 2019

AbstractWe present a model of the Hypothalamo-Adreno-Pituitary (HPA) system; our approach is hierarchical and biologically sound, reflecting the complexity of the real HPA system. The structure of the conceptual model is based on theoretical frameworks of biological complex systems and its implementation takes advantage of recent hybrid automata modelling and analysis tools, being modular and reflecting parameter and mechanisms uncertainties.
PharmOmics: A Species- and Tissue-specific Drug Signature Database and Online Tool for Drug Repurposing
Authors: Chen Yen-Wei , Diamante Graciel , Ding Jessica , Nghiem Thien Xuan , Yang Jessica , Ha Sung-min , Cohn Peter , Arneson Douglas , Blencowe Montgomery , Garcia Jennifer , Zaghari Nima , Patel Paul , Yang Xia 
Published: November 2019

AbstractDrug development has been hampered by a high failure rate in clinical trials due to efficacy or safety issues not predicted by preclinical studies in model systems. A key contributor is our incomplete understanding of drug functions across organ systems and species. Therefore, elucidating species- and tissue-specific actions of drugs can provide systems level insights into therapeutic efficacy, potential adverse effects, and interspecies differences that are necessary for more effective translational medicine. Here, we present a comprehensive drug knowledgebase and analytical tool, PharmOmics, comprised of genomic footprints of drugs in individual tissues from human, mouse, and rat transcriptome data from GEO, ArrayExpress, TG-GATEs, and DrugMatrix. Using multi-species and multi-tissue gene expression signatures as molecular indicators of drug functions, we developed gene network-based approaches for drug repositioning. We demonstrate the potential of PharmOmics to predict drugs for new disease indications and validated two predicted drugs for non-alcoholic fatty liver disease in mice. We also examined the potential of PharmOmics to identify drugs related to hepatoxicity and nephrotoxicity. By combining tissue- and species-specific in vivo drug signatures with biological networks, PharmOmics serves as a complementary tool to support drug characterization.
Revisiting use of DNA characters in taxonomy with MolD - a tree independent algorithm to retrieve diagnostic nucleotide characters from monolocus datasets
Authors: Fedosov Alexander , Achaz Guillaume , Puillandre Nicolas 
Published: November 2019

AbstractWhile DNA characters are increasingly used for phylogenetic inference, taxa delimitation and identification, their use for formal description of taxa (i.e. providing either a formal description or a diagnosis) remains scarce and inconsistent. The impediments are neither nomenclatural, nor conceptual, but rather methodological issues: lack of agreement of what DNA character should be provided, and lack of a suitable operational algorithm to identify such characters. Furthermore, the reluctance of using DNA data in taxonomy may also be due to the concerns of insufficient reliability of DNA characters as robustness of the DNA based diagnoses has never been thoroughly assessed. Removing these impediments will enhance integrity of systematics, and will enable efficient treatment of traditionally problematic cases, such as for example, cryptic species. We have developed a novel versatile and scalable algorithmMolDto recover diagnostic combinations of nucleotides (DNCs) for pre-defined groups of DNA sequences, corresponding to taxa. We applied MolD to four published monolocus datasets to examine 1) which type of DNA characters compilation allows for more robust diagnosis, and 2) how the robustness of DNA based diagnosis changes depending on the sampled fraction of taxons diversity. We demonstrate that the redundant DNCs, termed herein sDNCs, allow for higher robustness. Furthermore, we show that a reliable DNA-based diagnosis may be obtained when a rather small fraction of the entire data set is available. Based on our results we propose improvements to the existing practices of handling DNA data in taxonomic descriptions, and discuss a workflow of contemporary systematic study, where the integrative taxonomy part precedes the proposition of a DNA based diagnosis and the diagnosis itself can be efficiently used as a DNA barcode. Our analysis fills existing methodological gaps, thus setting stage for a wider use of the DNA data in taxa description.
Cellular and synaptic adaptations of neural circuits processing skylight polarization in the fly
Authors: Sancer Gizem , Kind Emil , Uhlhorn Juliane , Volkmann Julia , Hammacher Johannes , Pham Tuyen , Plazaola-Sasieta Haritz , Wernet Mathias F. 
Published: November 2019

AbstractSpecialized ommatidia harboring polarization-sensitive photoreceptors exist in the ‘dorsal rim area’ (DRA) of virtually all insects. Although downstream elements have been described both anatomically and physiologically throughout the optic lobes and the central brain of different species, little is known about their cellular and synaptic adaptations and how these shape their functional role in polarization vision. We have previously shown that in the DRA of Drosophila melanogaster, two distinct types of modality-specific ‘distal medulla’ cell types (Dm-DRA1 and Dm-DRA2) are post-synaptic to long visual fiber photoreceptors R7 and R8, respectively. Here we describe additional neuronal elements in the medulla neuropil that manifest modality-specific differences in the DRA region, including DRA-specific neuronal morphology, as well as differences in the structure of pre- or post-synaptic membranes. Furthermore, we show that certain cell types (medulla tangential cells and octopaminergic neuromodulatory cells) specifically avoid contacts with polarization-sensitive photoreceptors. Finally, while certain transmedullary cells are specifically absent from DRA medulla columns, other subtypes show specific wiring differences while still connecting the DRA to the lobula complex, as previously been described in larger insects. This hints towards a complex circuit architecture with more than one pathway connecting polarization-sensitive DRA photoreceptors with the central brain.
The urinary tract microbiome in older women exhibits host genetics and environmental influences
Authors: Adebayo AS , Ackermann G , Bowyer RC , Wells P , Humphreys G , Knight R , Spector TD , Steves CJ 
Published: November 2019

SummaryThe urinary microbiome is a relatively unexplored niche despite the fact that we now know that it is not sterile. Moreover urinary microbes, especially in ageing populations, are associated with morbidity even when infection is subsequently not proven. We present the first large-scale study to explore factors defining urinary microbiome composition in community-dwelling older adult women without clinically active infection. Using 1600 twins, we estimate the contribution of genetic and environmental factors to variation in microbiome using both 16S and shotgun metagenomics. We found that the urinary microbiome is distinct from nearby sites and is unrelated to stool microbiome. Core urinary microbiome taxa were defined. The first component of weighted unifrac was heritable (18%) as were key taxa (e.gEscherichia-Shigella(A>0.15)). Age, menopausal status, prior UTI and host genetics were top among factors defining the urobiome. Increased composition was associated with older age, contrary to previous findings.