bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary Care Quality Improvement Metrics and National Committee on Quality Assurance Medical Home Recognition for Children With Medical Complexity
Authors: Lail Jennifer , Fields Elise , Paolella Alyssa , Schoettker Pamela J. 
Published: December 2019

Introduction:
The Complex Care Center at Cincinnati Children’s Hospital Medical Center developed and implemented a set of evidence-based clinical process measures of immunization delivery, preventive and chronic condition laboratory screening, and behavioral health medication surveillance for use in the primary care setting.

Methods:
Improvement activities focused on 4 measures across 4 domains mandated by the National Committee on Quality Assurance for patient-centered medical home recognition. Interventions were implemented in phases from January 2017 to October 2018. The goal was the improvement in immunizations, preventive lead screening, vitamin D testing in chronic conditions, and behavioral health medication surveillance. Preventative lipid screening in the entire population and thyroid-stimulating hormone levels in patients with Down syndrome were also measured.

Results:
The offering and the completion of an immunization bundle increased from a mean of 61.0% to a mean of 83.7% of patients. Eligible patients with documented lead surveillance increased from 61.2% to 96.5%. Patients with documented 25-hydroxy vitamin D levels increased from 72.2% to 87.8%. The percentage of patients metabolically monitored while taking an atypical antipsychotic continued at 92.0%.

Conclusions:
Using quality improvement education, data measurement/feedback, electronic medical record optimization/decision support, and care gap identification with planned care, the Complex Care Center demonstrated improved reliability in needed immunization delivery and laboratory screenings for a heterogeneous primary care population of children with medical complexity. As the numbers of children with medical complexity rise, so does the importance of reliable processes and relevant measures for quality in their unique care delivery systems.
Epidemiological Analysis of Venous Malformation of the Orbit
Authors: Bonavolontà Paola , Fossataro Federica , Attanasi Federica , Clemente Lidia , Iuliano Adriana , Bonavolontà Giulio 
Published: December 2019

Abstract
Orbital venous malformation (OVM) is one of the most common orbital mass of adults, accounting for approximately 5% to 15% of all vascular abnormalities in the central nervous system and representing 9% of orbital lesions. Clinical presentation is variable from asymptomatic cases to symptomatic ones. The purpose of the authors’ work is to analyze OVM incidence and prevalence in a cohort of patients referred over the last 40 years to the Orbital Unit, tertiary center for orbital diseases.
Records of 224 patients diagnosed with CVM in a 40-year period were retrospectively reviewed extracting prevalence/year and incidence/year based on data obtained from Eurostat population statistics. Data were aggregate and analyzed with a Microsoft Excel (Microsoft Corporation, Redmond, WA) spread sheet.
The incidence rate was measured as the number of new cases of OVM observed in Orbital Unit, a tertiary center. Incidence was about 1 case out (0.94) every 10 million people. The incidence rate was measured also as the number of new cases of OVM observed in Campania, considering in the latter case patients residents in this region (112 patients). Incidence was less than 1 case out (0.58) every 10 million people.
The prevalence rate was measured as the proportion of individuals with OVM observed in our Orbital Unit and is equal to 5%. This indicator resulted to increase from 1977 to 2017.
The management of OVM is still under discussion, but in agreement with data present in the literature the authors still believe that the surgical indication is only for symptomatic lesions.
Toxic Optic Neuropathy From Quinine Overdose
Authors: Freund Paul R. , Wright Tom , Margolin Edward A. 
Published: December 2019

Abstract:
A 45-year-old man presented with longstanding poor vision in both eyes. His medical history was significant for a remote overdose of quinine. After the ingestion, he fell into a coma and on awakening was not able to see light out of both eyes. Several days later, his central vision began to gradually recover and continued to improve over the span of several months. Presently, he had 20/20 visual acuity in both eyes with severely constricted peripheral visual fields. There were bilateral iris transillumination defects, and both optic nerves were diffusely pale with attenuated vasculature and inner retinal thinning on ocular coherence tomography. We present a patient with the stereotypical findings and natural history of quinine toxicity, a rare and not widely known cause of toxic optic neuropathy and retinopathy.
Studying language in context using the temporal generalization method
Authors: Fyshe Alona 
Published: December 2019

The temporal generalization method (TGM) is a data analysis technique that can be used to test if the brain’s representation for particular stimuli (e.g. sounds, images) is maintained, or if it changes as a function of time (King J-R, Dehaene S. 2014 Characterizing the dynamics of mental representations: the temporal generalization method.Trends Cogn. Sci.18, 203–210. (doi:10.1016/j.tics.2014.01.002)). The TGM involves training models to predict the stimuli or condition using a time window from a recording of brain activity, and testing the resulting models at all possible time windows. This is repeated for all possible training windows to create a full matrix of accuracy for every combination of train/test window. The results of a TGM indicate when brain activity patterns are consistent (i.e. the trained model performs well even when tested on a different time window), and when they are inconsistent, allowing us to track neural representations over time. The TGM has been used to study the representation of images and sounds during a variety of tasks, but has been less readily applied to studies of language. Here, we give an overview of the method itself, discuss how the TGM has been used to analyse two studies of language in context and explore how the TGM could be applied to further our understanding of semantic composition.This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.
Modelling meaning composition from formalism to mechanism
Authors: Martin Andrea E. , Baggio Giosuè 
Published: December 2019

Human thought and language have extraordinary expressive power because meaningful parts can be assembled into more complex semantic structures. This partly underlies our ability to compose meanings into endlessly novel configurations, and sets us apart from other species and current computing devices. Crucially, human behaviour, including language use and linguistic data, indicates that composing parts into complex structures does not threaten the existence of constituent parts as independent units in the system: parts and wholes exist simultaneously yet independently from one another in the mind and brain. This independence is evident in human behaviour, but it seems at odds with what is known about the brain's exquisite sensitivity to statistical patterns: everyday language use is productive and expressive precisely because it can go beyond statistical regularities. Formal theories in philosophy and linguistics explain this fact by assuming that language and thought arecompositional: systems of representations that separate a variable (orrole) from its values (fillers), such that the meaning of a complex expression is a function of the values assigned to the variables. The debate on whether and how compositional systems could be implemented in minds, brains and machines remains vigorous. However, it has not yet resulted in mechanistic models of semantic composition: how, then, are the constituents of thoughts and sentences put and held together? We review and discuss current efforts at understanding this problem, and we chart possible routes for future research.This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.
The meaning-making mechanism(s) behind the eyes and between the ears
Authors: Hagoort Peter 
Published: December 2019

In this contribution, the following four questions are discussed: (i) where is meaning?; (ii) what is meaning?; (iii) what is the meaning of mechanism?; (iv) what are the mechanisms of meaning? I will argue that meanings are in the head. Meanings have multiple facets, but minimally one needs to make a distinction between single word meanings (lexical meaning) and the meanings of multi-word utterances. The latter ones cannot be retrieved from memory, but need to be constructed on the fly. A mechanistic account of the meaning-making mind requires an analysis at both a functional and a neural level, the reason being that these levels are causally interdependent. I will show that an analysis exclusively focusing on patterns of brain activation lacks explanatory power. Finally, I shall present an initial sketch of how the dynamic interaction between temporo-parietal areas and inferior frontal cortex might instantiate the interpretation of linguistic utterances in the context of a multimodal setting and ongoing discourse information.
This article is part of the theme issue ‘Towards mechanistic models of
meaning composition’
Sheaving—a universal construction for semantic compositionality
Authors: Phillips Steven 
Published: December 2019

Semantic compositionality—the way that meanings of complex entities obtain from meanings of constituent entities and their structural relations—is supposed to explain certain concomitant cognitive capacities, such as systematicity. Yet, cognitive scientists are divided on mechanisms for compositionality: e.g. a language of thought on one side versus a geometry of thought on the other. Category theory is a field of (meta)mathematics invented to bridge formal divides. We focus on sheaving—a construction at the nexus of algebra and geometry/topology, alluding to an integrative view, to sketch out a category theory perspective on the semantics of compositionality. Sheaving is a universal construction for making inferences from local knowledge, where meaning is grounded by the underlying topological space. Three examples illustrate how topology conveys meaning, in terms of the inclusion relations between the open sets that constitute the space, though the topology is not regarded as the only source of semantic information. In this sense, category (sheaf) theory provides a general framework for semantic compositionality.
This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.
Structured sequence processing and combinatorial binding: neurobiologically and computationally informed hypotheses
Authors: Calmus Ryan , Wilson Benjamin , Kikuchi Yukiko , Petkov Christopher I. 
Published: December 2019

Understanding how the brain forms representations of structured information distributed in time is a challenging endeavour for the neuroscientific community, requiring computationally and neurobiologically informed approaches. The neural mechanisms for segmenting continuous streams of sensory input and establishing representations of dependencies remain largely unknown, as do the transformations and computations occurring between the brain regions involved in these aspects of sequence processing. We propose a blueprint for a neurobiologically informed and informing computational model of sequence processing (entitled: Vector-symbolic Sequencing of Binding INstantiating Dependencies, or VS-BIND). This model is designed to support the transformation of serially ordered elements in sensory sequences into structured representations of bound dependencies, readily operates on multiple timescales, and encodes or decodes sequences with respect to chunked items wherever dependencies occur in time. The model integrates established vector symbolic additive and conjunctive binding operators with neurobiologically plausible oscillatory dynamics, and is compatible with modern spiking neural network simulation methods. We show that the model is capable of simulating previous findings from structured sequence processing tasks that engage fronto-temporal regions, specifying mechanistic roles for regions such as prefrontal areas 44/45 and the frontal operculum during interactions with sensory representations in temporal cortex. Finally, we are able to make predictions based on the configuration of the model alone that underscore the importance of serial position information, which requires input from time-sensitive cells, known to reside in the hippocampus and dorsolateral prefrontal cortex.This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.
Training neural networks to encode symbols enables combinatorial generalization
Authors: Vankov Ivan I. , Bowers Jeffrey S. 
Published: December 2019

Combinatorial generalization—the ability to understand and produce novel combinations of already familiar elements—is considered to be a core capacity of the human mind and a major challenge to neural network models. A significant body of research suggests that conventional neural networks cannot solve this problem unless they are endowed with mechanisms specifically engineered for the purpose of representing symbols. In this paper, we introduce a novel way of representing symbolic structures in connectionist terms—the vectors approach to representing symbols (VARS), which allows training standard neural architectures to encode symbolic knowledge explicitly at their output layers. In two simulations, we show that neural networks not only can learn to produce VARS representations, but in doing so they achieve combinatorial generalization in their symbolic and non-symbolic output. This adds to other recent work that has shown improved combinatorial generalization under some training conditions, and raises the question of whether specific mechanisms or training routines are needed to support symbolic processing.This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.
AlphaFamImpute: high accuracy imputation in full-sib families from genotype-by-sequencing data
Authors: Whalen Andrew , Gorjanc Gregor , Hickey John M 
Published: December 2019

AbstractSummaryAlphaFamImpute is an imputation package for calling, phasing, and imputing genome-wide genotypes in outbred full-sib families from single nucleotide polymorphism (SNP) array and genotype-by-sequencing (GBS) data. GBS data is increasingly being used to genotype individuals, especially when SNP arrays do not exist for a population of interest. Low-coverage GBS produces data with a large number of missing or incorrect naïve genotype calls, which can be improved by identifying shared haplotype segments between full-sib individuals. Here we present AlphaFamImpute, an algorithm specifically designed to exploit the genetic structure of full-sib families. It performs imputation using a two-step approach. In the first step it phases and imputes parental genotypes based on the segregation states of their offspring (that is, which pair of parental haplotypes the offspring inherited). In the second step it phases and imputes the offspring genotypes by detecting which haplotype segments the offspring inherited from their parents. With a series of simulations we find that AlphaFamImpute obtains high accuracy genotypes, even when the parents are not genotyped and individuals are sequenced at less than 1x coverage.Availability and implementationAlphaFamImpute is available as a Python package from the AlphaGenes website,http://www.AlphaGenes.roslin.ed.ac.uk/AlphaFamImpute.Contactawhalen@roslin.ed.ac.ukSupplementary informationA complete description of the methods is available in the supplementary information.
Compartment and cell type-specific hypoxia responses in the developingDrosophilabrain
Authors: Baccino-Calace Martin , Prieto Daniel , Cantera Rafael , Egger Boris 
Published: December 2019

ABSTRACTEnvironmental factors such as the availability of oxygen are instructive cues to regulate stem cell maintenance and differentiation. We used a genetically encoded biosensor to monitor the hypoxic state of neural cells in the larval brain ofDrosophila. The biosensor reveals brain compartment and cell type specific levels of hypoxia. The values correlate with differential tracheolation that is observed throughout development between the central brain and the optic lobe. Neural stem cells in both compartments show the strongest hypoxia response while intermediate progenitors, neurons and glial cells reveal weaker responses. We demonstrate that the distance between a cell and the next closest tracheole is a good predictor of the hypoxic state for that cell. Our model concludes that oxygen availability is the major factor controlling the hypoxia response in the developingDrosophilabrain but cell intrinsic and cell-type specific factors contribute to modulate the response in an unexpected manner.
An Extended Primer Grip of Picornavirus Polymerase Facilitates Sexual RNA Replication Mechanisms
Authors: Kempf Brian J. , Watkins Colleen L. , Peersen Olve B. , Barton David J 
Published: December 2019

ABSTRACTPicornaviruses have both asexual and sexual RNA replication mechanisms. Asexual RNA replication mechanisms involve one parental template whereas sexual RNA replication mechanisms involve two or more parental templates. Because sexual RNA replication mechanisms counteract ribavirin-induced error catastrophe, we selected for ribavirin-resistant poliovirus to identify polymerase residues that facilitate sexual RNA replication mechanisms. We used serial passage in ribavirin, beginning with a variety of ribavirin-sensitive and ribavirin-resistant parental viruses. Ribavirin-sensitive virus contained an L420A polymerase mutation while ribavirin-resistant virus contained a G64S polymerase mutation. A G64 codon mutation (G64Fix) was used to inhibit emergence of G64S-mediated ribavirin resistance. Revertants (L420) or pseudo-revertants (L420V, L420I) were selected from all independent lineages of L420A, G64FixL420A and G64S L420A parental viruses. Ribavirin-resistant G64S mutations were selected in two independent lineages and novel ribavirin-resistance mutations were selected in the polymerase in other lineages (M299I, M323I, M392V, T353I). The structural orientation of M392, immediately adjacent to L420 and the polymerase primer grip region, led us to engineer additional polymerase mutations into poliovirus (M392A, M392L & M392V and K375R & R376K). L420A revertants and pseudorevertants (L420V, L420I) restored efficient sexual RNA replication mechanisms, confirming that ribavirin-induced error catastrophe coincides with defects in sexual RNA replication mechanisms. Viruses containing M392 mutations (M392A, M392L & M392V) and primer grip mutations (K375R & R376K) exhibited divergent RNA recombination, ribavirin sensitivity and biochemical phenotypes, consistent with changes in the fidelity of RNA synthesis. We conclude that an extended primer grip of the polymerase, including L420, M392, K375 & R376, contributes to the fidelity of RNA synthesis and to efficient sexual RNA replication mechanisms.IMPORTANCEPicornaviruses have both asexual and sexual RNA replication mechanisms. Sexual RNA replication shapes picornavirus species groups, contributes to the emergence of vaccine-derived polioviruses and counteracts error catastrophe. Can viruses distinguish between homologous and non-homologous partners during sexual RNA replication? We implicate an extended primer grip of the viral polymerase in sexual RNA replication mechanisms. By sensing RNA sequence complementarity near the active site, the extended primer grip of the polymerase has the potential to distinguish between homologous and non-homologous RNA templates during sexual RNA replication.
Stretchable Composite Acoustic Transducer for Wearable Monitoring of Vital Signs
Authors: Cotur Yasin , Kasimatis Michael , Kaisti Matti , Olenik Selin , Georgiou Charis , Güder Firat 
Published: December 2019

AbstractWe report a highly flexible, stretchable, and mechanically robust low-cost soft composite consisting of silicone polymers and water (or hydrogels). When combined with conventional acoustic transducers, the materials reported enable high performance real-time monitoring of heart and respiratory patterns over layers of clothing (or furry skin of animals) without the need for direct contact with the skin. Our approach enables an entirely new method of fabrication that involves encapsulation of water and hydrogels with silicones and exploits the ability of sound waves to travel through the body. The system proposed outperforms commercial, metal-based stethoscopes for the auscultation of the heart when worn over clothing and is less susceptible to motion artefacts. We have tested the system both with human and furry animal subjects (i.e.dogs), primarily focusing on monitoring the heart, however, we also present initial results on monitoring breathing. Our work is especially important because it is the first demonstration of a stretchable sensor that is suitable for use with furry animals and do not require shaving of the animal for data acquisition.
Cell-specific exon methylation and CTCF binding in neurons regulates calcium ion channel splicing and function
Authors: Soto Eduardo Javier Lopez , Lipscombe Diane 
Published: December 2019

SummaryCell-specific alternative splicing modulates myriad cell functions and this process is disrupted in disease. The mechanisms governing alternative splicing are known for relatively few genes and typically focus on RNA splicing factors. In sensory neurons, cell-specific alternative splicing of the presynaptic voltage-gated calcium channelCacna1bgene modulates opioid sensitivity. How this splicing is regulated has remained unknown. We find that cell-specific exon DNA hypomethylation permits binding of CTCF, the master regulator of chromatin structure in mammals, which, in turn, controls splicing in noxious heat-sensing nociceptors.Hypomethylation of an alternative exon specifically in nociceptors allows for CTCF binding, and expression of CaV2.2 channels with increased opioid sensitivity. Following nerve injury, exon methylation is increased, and splicing is disrupted. Our studies define the molecular mechanisms of cell-specific alternative splicing of a functionally validated exon in normal and disease states – and reveal a potential target for the treatment of chronic pain.HighlightsThe molecular basis of cell-specific splicing of a synaptic calcium channel gene.Splicing controlled by cell-specific exon hypomethylation and CTCF binding.Peripheral nerve injury disrupts exon hypomethylation and splicing.Targeted demethylation of exon by dCAS9-TET modifies alternative splicing.GRAPHICAL ABSTRACTCell-specific epigenetic modifications in a synaptic calcium ion channel gene controls cell-specific splicing in normal and neuropathic pain.In naïve animals, in most neurons,Cacna1be37a locus is hipermethylated (5-mC) and CTCF does not bind this locus. During splicing, e37a is skipped andCacna1bmRNAs include e37b. In contrast, inTrpv1-lineage neurons,Cacna1be37a locus is hypomethylated and is permissive for CTCF binding. CTCF promotes e37a inclusion and bothCacna1be37a and e37b mRNAs are expressed. E37a confers strong sensitivity to the Cav2.2 channel to inhibition by μ-opioid receptors (μOR). Morphine is more effective at inhibiting e37a-containing Cav2.2 channels.After peripheral nerve injurythat results in pathological pain, methylation level ofCacna1be37a locus is increased, CTCF binding is impaired, andCacna1be37a mRNA levels are decreased. This disrupted splicing pattern is associated with reduced efficacy of morphinein vivo.