bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Strategy for the Renovation of a Clinical Pathways Program
Authors: Pugh-Bernard Aimee , Nickels Sarah , Melendez Jessieca , Shawkat Jehan , Rolison Elise , Swanson Angela , Bajaj Lalit , Hyman Daniel , Bakel Leigh Anne 
Published: June 2019

Introduction:
Clinical pathways (CPs) translate best available evidence to the local care context and intend to inform clinical decision-making, optimize care, and decrease variation. This article describes a CPs program improvement process at a free-standing academic children’s hospital. Aims: (1) improve the pathway development process; (2) identify and address gaps; (3) strengthen measurement; (4) increase efficiency in cycle time to build a pathway; (5) increase multidisciplinary participation; (6) integrate into the electronic health record ; and (7) and increase pathway utilization.

Methods:
We renovated the CP program using a structured, improvement process. A series of internal stakeholder and external colleague interviews informed the process. To improve the program, we developed and implemented different interventions.

Results:
The streamlined process reduced the overall time for completion from a median of 15 to 5 months (measured from the date of first meeting with the clinical improvement team to approval), a 70% increase in efficiency. Between 1994 and 2015, the hospital had 33 CPs. There was a 78% increase in the total number of pathways after the renovation with 26 additional pathways.

Conclusions:
Renovation of the CP program led to early success through an improved development process, alleviation of programmatic gaps, inclusion of measures within each pathway, increased timely completion, multidisciplinary involvement, integration into the electronic health record, and improved utilization. Initial results are encouraging, and the lessons learned should be helpful to other programs. Further program development is ongoing, focusing on continued improvements in implementation and overall program measures.
Development and Validation of HIV-ASSIST, an Online, Educational, Clinical Decision Support Tool to Guide Patient-Centered ARV Regimen Selection
Authors: Maddali Manoj V. , Mehtani Nicky J. , Converse Caro , Kapoor Sunaina , Pham Paul , Li Jonathan Z. , Shah Maunank 
Published: June 2019

Background:
Multiple antiretroviral (ARV) regimens are effective at achieving HIV viral suppression, but differ in pill burden, side effects, barriers to resistance, and impact on comorbidities. Current guidelines advocate for an individualized approach to ARV regimen selection, but synthesizing these modifying factors is complex and time-consuming.

Methods:
We describe the development of HIV-ASSIST (https://www.hivassist.com), a free, online decision support tool for ARV selection and HIV education. HIV-ASSIST ranks potential ARV options for any given patient scenario using a composite objective of achieving viral suppression while maximizing tolerability and adherence. We used a multiple-criteria decision analysis framework to construct mathematical algorithms and synthesize various patient-specific (eg, comorbidities and treatment history) and virus-specific (eg, HIV mutations) attributes. We then conducted a validation study to evaluate HIV-ASSIST with prescribing practices of experienced HIV providers at 4 large academic centers. We report on concordance of provider ARV selections with the 5 top-ranked HIV-ASSIST regimens for 10 diverse hypothetical patient-case scenarios.

Results:
In the validation cohort of 17 experienced HIV providers, we found 99% concordance between HIV-ASSIST recommendations and provider ARV selections for 4 case-scenarios of ARV-naive patients. Among 6 cases of ARV-experienced patients (3 with and 3 without viremia), there was 84% and 88% concordance, respectively. Among 3 cases of ARV-experienced patients with viremia, providers reported 20 different ARV selections, suggesting substantial heterogeneity in ARV preferences in clinical practice.

Conclusions:
HIV-ASSIST is a novel patient-centric educational decision support tool that provides ARV recommendations concordant with experienced HIV providers for a diverse set of patient scenarios.
Asymptomatic Bone Marrow Edema Detected by 67Ga Scintigraphy
Authors: Miwa Shinji , Otsuka Takanobu , Yamada Satoshi , Aiba Hisaki , Tsuchiya Hiroyuki 
Published: June 2019

Abstract
A 46-year-old woman presented with a complaint of fever. CRP was 2.1 mL/L in blood, white blood cell count was 20–29/hpf, and bacterial count was 3418/μL in a urinalysis. 67Ga scan revealed accumulation of 67Ga in the left distal femur, although she had no symptoms around the site. MRI demonstrated diffuse high signal intensity on T2-weighted STIR images. Osteomyelitis was suspected, and biopsy was performed. Bacterial culture of the bone marrow was negative, and histological examination showed no infiltration of inflammatory cells. Two months after the biopsy, disappearance of altered signal intensity of MRI was observed.
Using background noise to improve sound localization following simulated hearing loss
Authors: Ryan-Warden Lindsey , Ng Eva , Keating Peter 
Published: June 2019

AbstractMany listening abilities become more difficult in noisy environments, particularly following hearing loss. Sound localization can be disrupted even if target sounds are clearly audible and distinct from background noise. Since subjects locate sounds by comparing the input to the two ears, sound localization is also considerably impaired by unilateral hearing loss. Currently, however, it is unclear whether the effects of unilateral hearing loss are worsened by background noise. To address this, we measured sound localization abilities in the presence or absence of broadband background noise. Adult human subjects of either sex were tested with normal hearing or with a simulated hearing loss in one ear (earplug). To isolate the role of binaural processing, we tested subjects with narrowband target sounds. Surprisingly, we found that continuous background noise improved narrowband sound localization following simulated unilateral hearing loss. By contrast, we found the opposite effect under normal hearing conditions, with background noise producing illusory shifts in sound localization. Previous attempts to model these shifts are inconsistent with behavioural and neurophysiological data. However, here we found that a simple hemispheric model of sound localization provides an explanation for our results, and provides key hypotheses for future neurophysiological studies. Overall, our results suggest that continuous background noise may be used to improve sound localization under the right circumstances. This has important implications for real-world hearing, both in normal-hearing subjects and the hearing-impaired.Significance StatementIn noisy environments, many listening abilities become more difficult, even if target sounds are clearly audible. For example, background noise can produce illusory shifts in the perceived direction of target sounds. Because sound localization relies on the two ears working together, it is also distorted by a hearing loss in one ear. We might therefore expect background noise to worsen the effects of unilateral hearing loss. Surprisingly, we found the opposite, with background noise improving sound localization when we simulated a hearing loss in one ear. A simple hemispheric model of sound localization also helped explain the negative effects of background noise under normal hearing conditions. Overall, our results highlight the potential for using background noise to improve sound localization.
Molecular determinants of the Ska-Ndc80 interaction and their influence on microtubule tracking and force-coupling
Authors: Huis in ’t Veld Pim J. , Volkov Vladimir A. , Stender Isabelle , Musacchio Andrea , Dogterom Marileen 
Published: June 2019

AbstractErrorless chromosome segregation requires load-bearing attachments of the plus ends of spindle microtubules to chromosome structures named kinetochores. How these end-on kinetochore attachments are established following initial lateral contacts with the microtubule lattice is poorly understood. Two microtubule-binding complexes, the Ndc80 and Ska complexes, are important for efficient end-on coupling and may function as a unit in this process, but precise conditions for their interaction are unknown. Here, we report that the Ska-Ndc80 interaction is phosphorylation-dependent and does not require microtubules, applied force, or several previously identified functional determinants including the Ndc80-loop and the Ndc80-tail. Under force, Ska stabilizes end-on microtubule attachments in parallel with the Ndc80-tail, which we reveal to be essential for end-tracking by Ndc80 multimers. Modulation of force-coupling efficiency demonstrates that the duration of stalled microtubule disassembly predicts whether a microtubule is stabilized and rescued by the kinetochore, likely reflecting a structural transition of the microtubule end.Abstract Figure
Category-Selective Visual Regions Have Distinctive Signatures of Connectivity in Neonates
Authors: Cabral Laura , Zubiaurre Leire , Wild Conor , Linke Annika , Cusack Rhodri 
Published: June 2019

AbstractThe development of the ventral visual stream is shaped both by an innate proto-organization and by experience. The fusiform face area (FFA), for example, has stronger connectivity to early visual regions representing the fovea and lower spatial frequencies. In adults, category-selective regions in the ventral stream (e.g. the FFA) also have distinct signatures of connectivity to widely distributed brain regions, which are thought to encode rich cross-modal, motoric, and affective associations (e.g., tool regions to the motor cortex). It is unclear whether this long-range connectivity is also innate, or if it develops with experience. We used MRI diffusion-weighted imaging with tractography to characterize the connectivity of face, place, and tool category-selective regions in neonates (N=445), 1-9 month old infants (N=11), and adults (N=14). Using a set of linear-discriminant classifiers, category-selective connectivity was found to be both innate and shaped by experience. Connectivity for faces was the most developed, with no evidence of significant change in the time period studied. Place and tool networks were present at birth but also demonstrated evidence of development with experience, with tool connectivity developing over a more protracted period (9 months). Taken together, the results support an extended proto-organizon to include long-range connectivity that could provide additional constraints on experience dependent development.
Host mucin is subverted by Pseudomonas aeruginosa during infection to provide free glycans required for successful colonization
Authors: Hoffman Casandra L , Aballay Alejandro 
Published: June 2019

AbstractThe mucosal barrier, found lining epithelial cells, serves multiple functions in a range of animals. The major structural components of mucus are mucins, which are heavily glycosylated proteins that are either membrane bound or secreted by the epithelial cells. Mucins are key components of the innate immune system, as they are involved in the clearance of pathogens from the airways and intestines, and their expression is typically upregulated upon epithelial cell exposure to a variety of pathogens. In this study, we identified the mucin MUL-1 as an innate immune factor that appears to be utilized by P. aeruginosa to colonize hosts. We found that while the expression of several mucins, including MUL-1, increased upon P. aeruginosa infection of the nematode Caenorhabditis elegans, silencing of or deletion of mul-1 resulted in enhanced survival and reduced bacterial accumulation. P. aeruginosa required host sialidase CTSA-1.1 to use mucin-derived glycans to colonize the host, while sialidase-encoding bacteria required host MUL-1 but not CTSA-1.1 to cause a lethal infection. This role of mucins and free glycans in host-pathogen interaction appears to be conserved from C. elegans to humans, as P. aeruginosa binding to human lung epithelial cells was also enhanced in the presence of free glycans, and free glycans reversed the binding defect of P. aeruginosa to human lung cells lacking the mucin MUC1.Author SummaryThe gastrointestinal, respiratory, reproductive, and urinary tracts, are large surfaces exposed to the exterior environment and thus, these mucosal epithelial tissues serve as primary routes of infection. One of the first lines of defense present at these barriers is mucus, which is a highly viscous material formed by mucin glycoproteins. Mucins serve various functions, but importantly they aid in the clearance of pathogens and debris from epithelial barriers and serve as innate immune effectors. In this study, we describe the ability of Pseudomonas aeruginosa to utilize mucin-derived glycans to colonize the intestine and ultimately cause death in Caenorhabditis elegans. We also show conserved mechanisms of P. aeruginosa virulence traits, by demonstrating that free glycans alter the ability of the bacteria to bind to human lung alveolar epithelial cells. Over the course of host-pathogen evolution, pathogens seem to have evolved to use mucins for their own advantage, and thus one of the biggest questions is which party benefits from pathogen-mucin binding. By gaining a better understanding of pathogen-mucin interactions, we can better protect against pathogen infection.
Astrocyte subdomains respond independently in vivo
Authors: López-Hidalgo Mónica , Kellner Vered , Schummers James 
Published: June 2019

AbstractAstrocytes contact thousands of synapses throughout the territory covered by its fine bushy processes. Astrocytes respond to neuronal activity with an increase in calcium concentration that is in turn linked to their capacity to modulate neuronal activity. It remains unclear whether astrocytes behave as a single functional unit that integrates all of these inputs, or if multiple functional subdomains reside within an individual astrocyte. We utilized the topographic organization of ferret visual cortex to test whether local neuronal activity can elicit spatially restricted events within an individual astrocyte. We monitored calcium activity throughout the extent of astrocytes in ferret visual cortex while presenting visual stimuli that elicit coordinated neuronal activity spatially restricted to functional columns. We found visually-driven calcium responses throughout the entire astrocyte that was largely independent in individual subdomains, often responding to different visual stimulus orientations. A model of the spatial interaction of astrocytes and neuronal orientation maps recapitulated these measurements, consistent with the hypothesis that astrocyte subdomains integrate local neuronal activity. Together, these results suggest that astrocyte responses to neural circuit activity are dominated by functional subdomains that respond locally and independently to neuronal activity.
Multiple steps mediate ventricular layer attrition to form the adult mouse spinal cord central canal
Authors: Cañizares Marco A. , Albors Aida Rodrigo , Singer Gail , Suttie Nicolle , Gorkic Metka , Felts Paul , Storey Kate G. 
Published: June 2019

AbstractThe ventricular layer of the spinal cord is remodelled during embryonic development and ultimately forms the adult central canal, which retains neural stem cell potential. This anatomical transformation involves the process of dorsal collapse, however, accompanying changes in tissue organization and cell behaviour as well as the origin of cells contributing to the adult central canal are not well understood. Here we describe sequential localised cell rearrangements which contribute to the gradual attrition of the spinal cord ventricular layer during development. This includes local breakdown of the pseudostratified organisation of the dorsal ventricular layer prefiguring dorsal collapse and evidence for a new phenomenon, ventral dissociation, during which the ventral-most floor plate cells separate from a subset that are retained in the central canal. Using cell proliferation markers and cell-cycle reporter mice, we further show that following dorsal collapse, ventricular layer attrition involves an overall reduction in cell proliferation, characterised by an intriguing increase in the percentage of cells in G1/S. In contrast, programmed cell death does not contribute to ventricular layer remodelling. By analysing transcript and protein expression patterns associated with key signalling pathways, we provide evidence for a gradual decline in ventral sonic hedgehog activity and an accompanying ventral expansion of initial dorsal bone morphogenetic protein signalling, which comes to dominate the forming central canal. This study identifies multiple steps that contribute to spinal cord ventricular layer attrition and adds to increasing evidence for the heterogenous origin of the adult spinal cord central canal, which includes cells from the floor plate and the roof plate as well as ventral progenitor domain.
Evaluating Protein Transfer Learning with TAPE
Authors: Rao Roshan , Bhattacharya Nicholas , Thomas Neil , Duan Yan , Chen Xi , Canny John , Abbeel Pieter , Song Yun S. 
Published: June 2019

AbstractProtein modeling is an increasingly popular area of machine learning research. Semi-supervised learning has emerged as an important paradigm in protein modeling due to the high cost of acquiring supervised protein labels, but the current literature is fragmented when it comes to datasets and standardized evaluation techniques. To facilitate progress in this field, we introduce the Tasks Assessing Protein Embeddings (TAPE), a set of five biologically relevant semi-supervised learning tasks spread across different domains of protein biology. We curate tasks into specific training, validation, and test splits to ensure that each task tests biologically relevant generalization that transfers to real-life scenarios. We bench-mark a range of approaches to semi-supervised protein representation learning, which span recent work as well as canonical sequence learning techniques. We find that self-supervised pretraining is helpful for almost all models on all tasks, more than doubling performance in some cases. Despite this increase, in several cases features learned by self-supervised pretraining still lag behind features extracted by state-of-the-art non-neural techniques. This gap in performance suggests a huge opportunity for innovative architecture design and improved modeling paradigms that better capture the signal in biological sequences. TAPE will help the machine learning community focus effort on scientifically relevant problems. Toward this end, all data and code used to run these experiments are available at https://github.com/songlab-cal/tape.
Intertrial Variability in Human Corticospinal Activity during Grasp Force Planning
Authors: Rao Nishant , Parikh Pranav J. 
Published: June 2019

ABSTRACTNeuronal firing rate variability during planning has been found to contribute to trial-to-trial variability in primate behavior. However, in humans, whether planning related mechanisms contribute to trial-to-trial behavioral variability remains unknown. We investigated the time-course of trial-to-trial variability in corticospinal excitability (CSE) using transcranial magnetic stimulation (TMS) while subjects planned to perform a self-paced reach-to-grasp task. We hypothesized that CSE variability will be modulated during task planning and that such a modulation would explain trial-to-trial behavioral variability. Able-bodied individuals were visually cued to plan their grip force before exertion of either 30% or 5% of maximum force on an object. TMS was delivered at different time points following a cue that instructed the force level. We first modeled the relation between CSE magnitude and its variability at rest (n=12) to study the component of CSE variability during task planning that was not related to changes in CSE magnitude (n=12). We found an increase in CSE variability during task planning at 30% but not at 5% of force. This effect was temporally dissociated from the decrease in CSE magnitude. Importantly, the increase in CSE variability during planning explained 64% of inter-individual differences in time to peak force rate trial-to-trial variability. These results were found to be repeatable across studies and robust to different analysis methods. Our findings suggest that the planning-related mechanisms underlying modulation in CSE variability and CSE magnitude are distinct. Notably, the extent of modulation in planning-related variability in corticospinal system within individuals may explain their trial-to-trial behavioral variability.
Comparativein silicoanalysis offtsZgene from different bacteria reveals the preference for core set of codons in coding sequence structuring and secondary structural elements determination
Authors: Pal Ayon , Saha Barnan Kr , Saha Jayanti 
Published: June 2019

AbstractThe deluge of sequence information in the recent times provide us with an excellent opportunity to compare organisms on a large genomic scale. In this study we have tried to decipher the variation in the gene organization and structuring of a vital bacterial gene calledftsZwhich codes for an integral component of the bacterial cell division, the FtsZ protein. FtsZ is homologous to tubulin protein and has been found to be ubiquitous in eubacteria. FtsZ is showing increasing promise as a target for antibacterial drug discovery. Our study offtsZprotein from 143 different bacterial species spanning a wider range of morphological and physiological type demonstrates that theftsZgene of about ninety three percent of the organisms involved in our analyses show relatively biased codon usage profile and significant GC deviation from their genomic GC content. We have also detected a tendency among the different organisms to utilize a core set of codons in structuring theftsZcoding sequence. Our meticulous analysis of theftsZgene linked with the corresponding FtsZ protein show that there is a bias towards the use of specific synonymous codons particularly in the helix and strand regions of the multi-domain FtsZ protein. Overall our findings suggest that in an indispensable and vital protein such as FtsZ, there is an inherent tendency to maintain form and structure for optimized performance in spite of the extrinsic variability in coding features.