bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel advances in monitoring and therapeutic approaches in idiopathic intracranial hypertension
Authors: Mitchell James L. , Mollan Susan P. , Vijay Vivek , Sinclair Alexandra J. 
Published: March 2019

Purpose of review
The current article appraises the recent developments in idiopathic intracranial hypertension (IIH), with particular attention to novel therapeutic avenues and advanced clinical assessment and monitoring with optical coherence tomography and telemetric intracranial pressure devices.

Recent findings
The incidence of IIH is increasing. The first consensus guidelines for IIH have been published detailing investigation and management algorithms for adult IIH. Improved understanding, clinical assessment and monitoring are emerging with the use of optical coherence tomography. Intracranial pressure telemetry is providing unique insights into the physiology of raised intracranial pressure in IIH. There are now an increasing number of ongoing clinical trials evaluating weight loss methods and novel targeted therapies, such as 11ß-HSD1 inhibition and Glucagon-like peptide 1 (GLP-1) receptor agonists.

Summary
Several studies are evaluating new therapies for IIH. Monitoring techniques are advancing, aiding diagnosis and allowing the clinician to accurately evaluate changes in papilloedema and intracranial pressure.
The unique role of the trigeminal autonomic reflex and its modulation in primary headache disorders
Authors: Möller Maike , May Arne 
Published: March 2019

Purpose of review
The trigeminal autonomic reflex is a physiological reflex with an important protective function which also plays a role in pathophysiological conditions, such as primary headache. It is not understood whether the autonomic symptoms in trigeminal autonomic cephalalgias and migraine are the consequence of severe trigeminal discharge or indeed directly driven by central generators as part of the pathophysiology, underlying these syndromes.

Recent findings
Modulating this reflex, and particularly the parasympathetic reflex arc, has been shown to be effective in treating headache. Among these modulators, left noninvasive vagal nerve stimulation has been shown to bilaterally inhibit the parasympathetic output of the reflex. Furthermore, the peripheral activation of the reflex, resulting in parasympathetic discharge, is not sufficient to provoke headache attacks in cluster headache patients, suggesting a central modulation.

Summary
Here, we review the anatomy and physiology of the trigeminal autonomic reflex and its involvement in primary headache. Possible candidates who have a modulating effect, including neurostimulation and pharmacological approaches, are described.
On the existence of elastic minimizers for initially stressed materials
Authors: Riccobelli D. , Agosti A. , Ciarletta P. 
Published: March 2019

A soft solid is said to be initially stressed if it is subjected to a state of internal stress in its unloaded reference configuration. In physical terms, its stored elastic energy may not vanish in the absence of an elastic deformation, being also dependent on the spatial distribution of the underlying material inhomogeneities. Developing a sound mathematical framework to model initially stressed solids in nonlinear elasticity is key for many applications in engineering and biology. This work investigates the links between the existence of elastic minimizers and the constitutive restrictions for initially stressed materials subjected to finite deformations. In particular, we consider a subclass of constitutive responses in which the strain energy density is taken as a scalar-valued function of both the deformation gradient and the initial stress tensor. The main advantage of this approach is that the initial stress tensor belongs to the group of divergence-free symmetric tensors satisfying the boundary conditions in any given reference configuration. However, it is still unclear which physical restrictions must be imposed for the well-posedness of this elastic problem. Assuming that the constitutive response depends on the choice of the reference configuration only through the initial stress tensor, under given conditions we prove the local existence of a relaxed state given by an implicit tensor function of the initial stress distribution. This tensor function is generally not unique, and can be transformed according to the symmetry group of the material at fixed initial stresses. These results allow one to extend Ball's existence theorem of elastic minimizers for the proposed constitutive choice of initially stressed materials.
This article is part of the theme issue ‘Rivlin's legacy in continuum mechanics and applied mathematics’.
The lncRNA NEAT1_1 is dispensable for normal tissue homeostasis and cancer cell growth
Authors: Adriaens Carmen , Rambow Florian , Bervoets Greet , Silla Toomas , Mito Mari , Chiba Tomoki , Hiroshi Asahara , Hirose Tetsuro , Nakagawa Shinichi , Jensen Torben Heick , Marine Jean-Christophe 
Published: March 2019

AbstractNEAT1 is one of the most studied lncRNAs, in part because its silencing in mice causes defects in mammary gland development and corpus luteum formation, and protects them from skin cancer development. Moreover, depleting NEAT1 in established cancer cell lines reduces growth and sensitizes cells to DNA damaging agents. However, NEAT1 produces two isoforms and because the short isoform, NEAT1_1, completely overlaps the 5’ part of the long NEAT1_2 isoform, the respective contributions of each of the isoforms to these phenotypes has remained unclear. Whereas NEAT1_1 is highly expressed in most tissues, NEAT1_2 is the central architectural component of paraspeckles, which are nuclear bodies that assemble in specific tissues and cells exposed to various forms of stress. Using dual RNA-FISH to detect both NEAT1_1 outside of paraspeckles and NEAT1_2/NEAT1 inside this nuclear body, we report herein that NEAT1_1 levels are dynamically regulated during the cell cycle and targeted for degradation by the nuclear RNA exosome. Unexpectedly, however, cancer cells engineered to lack NEAT1_1, but not NEAT1_2, do not exhibit cell cycle defects. Moreover, Neat1_1-specific knockout mice do not exhibit the phenotypes observed in Neat1-deficient mice. We propose that NEAT1 functions are mainly, if not exclusively, attributable to NEAT1_2 and, by extension, to paraspeckles.
Graphical abstract
Studying ecosystems with DNA metabarcoding: lessons from aquatic biomonitoring
Authors: Bush Alex , Compson Zacchaeus , Monk Wendy , Porter Teresita M. , Steeves Royce , Emilson Erik , Gagne Nellie , Hajibabaei Mehrdad , Roy Mélanie , Baird Donald J. 
Published: March 2019

AbstractAn ongoing challenge for ecological studies has been the collection of data with high precision and accuracy at a sufficient scale to detect effects relevant to management of critical global change processes. A major hurdle for many workflows has been the time-consuming and challenging process of sorting and identification of organisms, but the rapid development of DNA metabarcoding as a biodiversity observation tool provides a potential solution. As high-throughput sequencing becomes more rapid and cost-effective, a ‘big data’ revolution is anticipated, based on higher and more accurate taxonomic resolution, more efficient detection, and greater sample processing capacity. These advances have the potential to amplify the power of ecological studies to detect change and diagnose its cause, through a methodology termed ‘Biomonitoring 2.0’.Despite its promise, the unfamiliar terminology and pace of development in high-throughput sequencing technologies has contributed to a growing concern that an unproven technology is supplanting tried and tested approaches, lowering trust among potential users, and reducing uptake by ecologists and environmental management practitioners. While it is reasonable to exercise caution, we argue that any criticism of new methods must also acknowledge the shortcomings and lower capacity of current observation methods. Broader understanding of the statistical properties of metabarcoding data will help ecologists to design, test and review evidence for new hypotheses.We highlight the uncertainties and challenges underlying DNA metabarcoding and traditional methods for compositional analysis, focusing on issues of taxonomic resolution, sample similarity, taxon misidentification, sample contamination, and taxon abundance. Using the example of freshwater benthic ecosystems, one of the most widely-applied non-microbial applications of DNA metabarcoding to date, we explore the ability of this new technology to improve the quality and utility of ecological data, recognising that the issues raised have widespread applicability across all ecosystem types.
Rational use of Episodic and Working Memory: A Normative Account of Prospective Memory
Authors: Momennejad Ida , Lewis-Peacock Jarrod , Norman Kennneth A. , Cohen Jonathan , Singh Satinder , Lewis Richard L. 
Published: March 2019

AbstractHumans often simultaneously pursue multiple plans at different time scales. The successful realization of non-immediate plans (e.g., post package after work) requires keeping track of a future plan while accomplishing other intermediate tasks (e.g., write a paper), a capacity known as prospective memory. This capacity requires the integration of noisy evidence from perceptual input with evidence from short-term working memory (WM) and longer-term or episodic memory (LTM/EM). Here we formulate a set of dual-task problems in empirical studies of prospective memory as problems of computational rationality, and ask how a rational model should exploit noisy perception and memory to maximize payoffs. The model combines reinforcement learning (optimal action selection) with evidence accumulation (optimal inference) in order to derive good decision parameters for optimal task performance (i.e., performing an ongoing task while monitoring for a cue that triggers executing a second prospective task). We compare model behavior to key accuracy and reaction time phenomena in human performance. Thus, we offer a normative approach to theorizing and modeling these phenomena without assumptions about mechanisms of attention or retrieval. This approach can be extended to study meta-parameters governing the boundedly rational use of memory in planned action in health, as well as compensatory mnemonic strategies that may be rational responses to disturbances of these mechanisms in neuropsychiatric disorders.
Variation in phosphorus and sulfur content shapes the genetic architecture and phenotypic associations within wheat grain ionome
Authors: Fatiukha Andrii , Klymiuk Valentina , Peleg Zvi , Saranga Yehoshua , Cakmak Ismail , Krugman Tamar , Korol Abraham B. , Fahima Tzion 
Published: March 2019

SummaryDissection of the genetic basis of ionome is crucial for the understanding of the physiological and biochemical processes underlying mineral accumulation in seeds, as well as for efficient crop breeding. Most of the elements essential for plants are metals stored in seeds as chelate complexes with phytic acid or sulfur-containing compounds. We assume that the involvement of phosphorus and sulfur in metal chelation is the reason for strong phenotypic associations within ionome. Thus, we adjusted element concentrations for the effect of variation in phosphorus and sulfur seed content. The genetic architecture of wheat grain ionome was characterize by QTL analysis using a cross between durum and wild emmer wheat. Adjustment for variation in P and S drastically changed phenotypic associations within ionome and considerably improved QTL detection power and accuracy, resulting in identification of 105 QTLs and 437 QTL effects for 11 elements. A search for candidate genes revealed some strong functional associations of genes involved in transport and metabolism of ions and elements. Thus, we have shown that accounting for variation in P and S is crucial for understanding of the physiological and genetic regulation of mineral composition of wheat grain ionome and can be implemented for other plants.
Enhancing DNA metabarcoding performance and applicability with bait capture enrichment and DNA from conservative ethanol
Authors: Gauthier M. , Konecny-Dupré L. , Nguyen A. , Elbrecht V. , Datry T. , Douady C.J. , Lefébure T. 
Published: March 2019

ABSTRACTMetabarcoding is often presented as an alternative identification tool to compensate for coarse taxonomic resolution and misidentification encountered with traditional morphological approaches. However, metabarcoding comes with two major impediments which slow down its adoption. First, the picking and destruction of organisms for DNA extraction are time and cost consuming and do not allow organism conservation for further evaluations. Second, current metabarcoding protocols include a PCR enrichment step which induces errors in the estimation of species diversity and relative biomasses. In this study, we first evaluated the capacity of capture enrichment to replace PCR enrichment using controlled freshwater macrozoobenthos mock communities. Then, we tested if DNA extracted from the fixative ethanol (etDNA) of the same mock communities can be used as an alternative to DNA extracted from pools of whole organisms (bulk DNA). We show that capture enrichment provides more reliable and accurate representation of species occurrences and relative biomasses in comparison with PCR enrichment for bulk DNA. While etDNA does not permit to estimate relative biomasses, etDNA and bulk DNA provide equivalent species detection rates. Thanks to its robustness to mismatches, capture enrichment is already an efficient alternative to PCR enrichment for metabarcoding and, if coupled to etDNA, is a time-saver option in studies where presence information only is sufficient.
Metabolic activity affects response of single cells to a nutrient switch in structured populations
Authors: Dal Co Alma , Ackermann Martin , van Vliet Simon 
Published: March 2019

AbstractMicrobes live in ever-changing environments where they need to adapt their metabolism to different nutrient conditions. Many studies have characterized the response of genetically identical cells to nutrient switches in homogenous cultures, however in nature microbes often live in spatially structured groups such as biofilms where cells can create metabolic gradients by consuming and releasing nutrients. Consequently, cells experience different local microenvironments and vary in their phenotype. How does this phenotypic variation affect the ability of cells to cope with nutrient switches? Here we address this question by growing dense populations of Escherichia coli in microfluidic chambers and studying a switch from glucose to acetate at the single cell level. Before the switch, cells vary in their metabolic activity: some grow on glucose while others cross-feed on acetate. After the switch, only few cells can resume growth after a period of lag. The probability to resume growth depends on a cells’ phenotype prior to the switch: it is highest for cells crossfeeding on acetate, while it depends in a non-monotonic way on growth rate for cells growing on glucose. Our results suggest that the strong phenotypic variation in spatially structured populations might enhance their ability to cope with fluctuating environments.
BigBrain 3D atlas of cortical layers: cortical and laminar thickness gradients diverge in sensory and motor cortices
Authors: Wagstyl Konrad , Larocque Stéphanie , Cucurull Guillem , Lepage Claude , Cohen Joseph Paul , Bludau Sebastian , Palomero-Gallagher Nicola , Lewis Lindsay B. , Funck Thomas , Spitzer Hannah , Dicksheid Timo , Fletcher Paul C , Romero Adriana , Zilles Karl , Amunts Katrin , Bengio Yoshua , Evans Alan C. 
Published: March 2019

AbstractHistological atlases of the cerebral cortex, such as those made famous by Brodmann and von Economo, are invaluable for understanding human brain microstructure and its relationship with functional organization in the brain. However, these existing atlases are limited to small numbers of manually annotated samples from a single cerebral hemisphere, measured from 2D histological sections. We present the first whole-brain quantitative 3D laminar atlas of the human cerebral cortex. This atlas was derived from a 3D histological model of the human brain at 20 micron isotropic resolution (BigBrain), using a convolutional neural network to segment, automatically, the cortical layers in both hemispheres. Our approach overcomes many of the historical challenges with measurement of histological thickness in 2D and the resultant laminar atlas provides an unprecedented level of precision and detail.We utilized this BigBrain cortical atlas to test whether previously reported thickness gradients, as measured by MRI in sensory and motor processing cortices, were present in a histological atlas of cortical thickness, and which cortical layers were contributing to these gradients. Cortical thickness increased across sensory processing hierarchies, primarily driven by layers III, V and VI. In contrast, fronto-motor cortices showed the opposite pattern, with decreases in total and pyramidal layer thickness. These findings illustrate how this laminar atlas will provide a link between single-neuron morphology, mesoscale cortical layering, macroscopic cortical thickness and, ultimately, functional neuroanatomy.
A deep learning framework for nucleus segmentation using image style transfer
Authors: Hollandi Reka , Szkalisity Abel , Toth Timea , Tasnadi Ervin , Molnar Csaba , Mathe Botond , Grexa Istvan , Molnar Jozsef , Balind Arpad , Gorbe Mate , Kovacs Maria , Migh Ede , Goodman Allen , Balassa Tamas , Koos Krisztian , Wang Wenyu , Bara Norbert , Kovacs Ferenc , Paavolainen Lassi , Danka Tivadar , Kriston Andras , Carpenter Anne E. , Smith Kevin , Horvath Peter 
Published: March 2019

AbstractSingle cell segmentation is typically one of the first and most crucial tasks of image-based cellular analysis. We present a deep learning approach aiming towards a truly general method for localizing nuclei across a diverse range of assays and light microscopy modalities. We outperform the 739 methods submitted to the 2018 Data Science Bowl on images representing a variety of realistic conditions, some of which were not represented in the training data. The key to our approach is to adapt our model to unseen and unlabeled data using image style transfer to generate augmented training samples. This allows the model to recognize nuclei in new and different experiments without requiring expert annotations.
Evaluation of Gene Expression and Phenotypic Profiling Data as Quantitative Descriptors for Predicting Drug Targets and Mechanisms of Action
Authors: Lapins Maris , Spjuth Ola 
Published: March 2019

AbstractProfiling drug leads by means of in silico and in vitro assays as well as omics is widely used in drug discovery for safety and efficacy predictions. In this study, we evaluate the performance of machine learning models trained on data from gene expression and phenotypic profiling assays, with models trained on chemical structure descriptors, for prediction of various drug mechanisms of action and target proteins. Models for several hundred mechanisms of actions and targets were trained using data on 1484 compounds characterized in both gene expression using L1000 profiles, and phenotypic profiling with cell painting assay. The results indicate that the accuracy of the three profiling technologies varies for different endpoints, and indicate a clear potential synergistic effect if these methods are combined. We also study the effect of predictive accuracy of data from different cell lines for L1000 profiles, showing that the choice of cell line has a non-negligible effect on the predictive accuracy. The results strengthen the idea of integrated approaches for predicting drug targets and mechanisms of action in preclinical drug discovery.
Regulation of hippocampal memory by mTORC1 in somatostatin interneuron: Hippocampal SOM interneurons, mTORC1 and memory
Authors: Artinian J. , Jordan A. , Khlaifia A. , Honoré E. , La Fontaine A. , Racine A-S. , Laplante I. , Lacaille J-C. 
Published: March 2019

AbstractTranslational control of long-term synaptic plasticity via Mechanistic Target Of Rapamycin Complex 1 (mTORC1) is crucial for hippocampal learning and memory. The role of mTORC1 is well-characterized in excitatory principal cells but remains largely unaddressed in inhibitory interneurons. Here we used cell type-specific conditional knockout strategies to alter mTORC1 function selectively in somatostatin (SOM) inhibitory interneurons (SOM-INs). We found that up- and down-regulation of SOM-IN mTORC1 activity bi-directionally regulates contextual fear and spatial memory consolidation. Moreover, contextual fear learning induced a metabotropic glutamate receptor type 1 (mGluR1) mediated long-term potentiation (LTP) of excitatory input synapses onto hippocampal SOM-INs, that was dependent on mTORC1. Finally, the induction protocol for mTORC1-mediated late-LTP in SOM-INs regulated Schaffer collateral pathway LTP in pyramidal neurons. Thus, mTORC1 activity in somatostatin interneurons contributes to learning-induced persistent plasticity of their excitatory synaptic inputs and hippocampal memory consolidation, uncovering a role of mTORC1 in inhibitory circuits for memory.
Very severe anemia and one year mortality outcome after hospitalization in Tanzanian children: A prospective cohort study
Authors: Chami Neema , Hau Duncan K. , Masoza Tulla S. , Smart Luke R. , Kayange Neema M. , Hokororo Adolfine , Ambrose Emmanuela E. , Moschovis Peter P. , Wiens Matthew O. , Peck Robert N. 
Published: March 2019

AbstractBackgroundAfrica has the highest rates of child mortality. Little is known about outcomes after hospitalization for children with very severe anemia.ObjectiveTo determine one year mortality and predictors of mortality in Tanzanian children hospitalized with very severe anemia.MethodsWe conducted a prospective cohort study enrolling children 2-12 years hospitalized from August 2014 to November 2014 at two public hospitals in northwestern Tanzania. Children were screened for anemia and followed until 12 months after discharge. The primary outcome measured was mortality. Predictors of mortality were determined using Cox regression analysis.ResultsOf the 505 children, 90 (17.8%) had very severe anemia and 415 (82.1%) did not. Mortality was higher for children with very severe anemia compared to children without over a one year period from admission, 27/90 (30.0%) vs. 59/415 (14.2%) respectively (Hazard Ratio (HR) 2.42, 95% Cl 1.53–3.83). In-hospital mortality was 11/90 (12.2%) and post-hospital mortality was 16/79 (20.2%) for children with very severe anemia. The strongest predictors of mortality were age (HR 1.01, 95% Cl 1.00–1.03) and decreased urine output (HR 4.30, 95% Cl 1.04 – 17.7).ConclusionsChildren up to 12 years of age with very severe anemia have nearly a 30% chance of mortality following admission over a one year period, with over 50% of mortality occurring after discharge. Post-hospital interventions are urgently needed to reduce mortality in children with very severe anemia, and should include older children.