bluuebunny/crossref_metadata_2025_split huggingface dataset:
Same-Day Patient Consultation and Cochlear Implantation: Innovations in Patient-Centered Health Care Delivery
Authors: Nassiri Ashley M. , Yawn Robert J. , Gifford René H. , Holder Jourdan T. , Stimson C. J. , Eavey Roland D. , Haynes David S. 
Published: October 2019

Objective:
To develop and implement a streamlined, patient-centered service delivery model for patients referred for cochlear implantation (CI) at a high-volume academic center.

Patients:
CI candidate adults.

Interventions:
CI, implementation of new CI delivery model.

Main Outcome Measures:
Referral-to-surgery time, patient travel burden.

Results:
Data from 206 adults that underwent CI were used to develop a process map of the initial operational state from referral date to day of surgery (referral-to-surgery time). The initial referral-to-surgery time was 136 days on average, yet the average total work time by all involved providers was 17.6 hours. Prolonged wait times were associated with the following preoperative tasks: appointment scheduling, insurance approval, device ordering and shipment, and surgical scheduling. Patients traveled to the institution on at least two occasions for appointments. A new bundled, patient-centered CI delivery model was developed to address prolonged wait times, travel burden, and process inefficiencies. The new model implemented an interactive electronic medical record, coordinated appointments with same-day surgery, and stocked device inventory to reduce the referral-to-surgery time to 24 days—an improvement of 112 days. In the new model, new patient consultation and surgery were completed in one day, reducing the patient travel burden to the institution.

Conclusions:
The new CI program demonstrates that delivery innovations can have a substantial impact on measures of patient convenience and experience, and that these results are achievable without new technologies or changes in medical management. With a focus on patient-centered design, health care delivery models can be augmented to increase value for patients.
Metastatic Nasopharyngeal Carcinoma Treated With Intraarterial Combined With Intravenous Peptide Receptor Radionuclide Therapy
Authors: Zhu Wenjia , Zhang Jingjing , Singh Aviral , Kulkarni Harshad R. , Baum Richard P. 
Published: October 2019

Abstract
Nasopharyngeal carcinoma may express somatostatin receptors (SSTR). We present a case with metastatic nasopharyngeal carcinoma in the liver, bone, and lymph nodes. The patient was in progression after chemotherapy, external beam radiation therapy (ERBT), atezolizumab, and cetuximab. Due to strong SSTR expression of the metastases, PRRT was applied. After 3 cycles of intravenous 177Lu-DOTATOC and 1 cycle of intraarterial 90Y-DOTATOC therapy, the hepatic and bone metastases showed excellent response after PRRT. No nephrotoxicity or myelotoxicity was observed.
Population genomic evidence that human and animal infections in Africa come from the same populations ofDracunculus medinensis
Authors: Durrant Caroline , Thiele Elizabeth A. , Holroyd Nancy , Doyle Stephen R , Sallé Guillaume , Tracey Alan , Sankaranaranayan Geetha , Lotkowska Magda E. , Bennett Hayley M. , Huckvale Thomas , Abdellah Zahra , Tchindebet Ouakou , Wossen Mesfin , Yibi Logora Makoy Samuel , Coulibaly Cheick Oumar , Weiss Adam , Schulte-Hostedde Albrecht I , Foster Jeremy , Cleveland Christopher A. , Yabsley Michael J. , Ruiz-Tiben Ernesto , Berriman Matthew , Eberhard Mark L. , Cotton James A. 
Published: October 2019

AbstractBackgroundGuinea worm –Dracunculus medinensis– was historically one of the major parasites of humans and has been known since antiquity. Now, Guinea worm is on the brink of eradication, as efforts to interrupt transmission have reduced the annual burden of disease from millions of infections per year in the 1980s to only 30 human cases reported globally last year. Despite the enormous success of eradication efforts to date, one complication has arisen. Over the last few years, hundreds of dogs have been found infected with this previously apparently anthroponotic parasite, almost all in Chad. Moreover, the relative numbers of infections in humans and dogs suggests that dogs may be key in maintaining transmission in that country.ResultsIn an effort to shed light on this peculiar epidemiology of Guinea worm in Chad, we have sequenced and compared the genomes of worms from dog, human and other animal infections. Confirming previous work with other molecular markers, we show that all of these worms areD. medinensis, and that the same population of worms are causing both infections, can confirm the suspected transmission between host species and detect signs of a population bottleneck due to the eradication efforts. The diversity of worms in Chad appears to exclude the possibility that there were no, or very few, worms present in the country during a 10-year absence of reported cases.ConclusionsThis work reinforces the importance of adequate surveillance of both human and dog populations in the Guinea worm eradication campaign and suggests that control programs should stay aware of the possible emergence of unusual epidemiology as they approach elimination.
Mechanics of snake biting: Experiments and modelling
Authors: Kundanati Lakshminath , Guarino Roberto , Menegon Michele , Pugno Nicola M. 
Published: October 2019

AbstractAmong all the vertebrates, snakes possess the most sophisticated venom delivering system using their fangs. Fangs of many animals are well adapted to the mechanical loads experienced during the functions such as breaking the diet and puncturing the skin of the prey. Thus, investigation and modelling of puncturing mechanics of snakes is of importance to understand the form-function relationship of the fangs and tissue-fang interactions in detail. We have thus chosen fangs of two snake species i.e. viper (Bitis arietans) and burrowing snake (Atractaspis aterrima), with different shape and size and performed insertion experiments using tissue phantoms. Our results showed that both the species have similar mechanical properties but there was a difference in the insertion forces owing to the difference in shape of the fang. Also, our modelling of the fang-tissue interactions predicted some parameters close to the experimental values. Thus, our study can help in the development of bioinspired needles that can potentially have reduced insertion forces and less damage to the tissue.
Intercellular transmission of a bacterial cytotoxic prion-like protein in mammalian cells
Authors: Revilla-García Aida , Fernández Cristina , Álamo María Moreno-del , de los Ríos Vivian , Vorberg Ina M. , Giraldo Rafael 
Published: October 2019

AbstractRepA is a bacterial protein that builds intracellular amyloid oligomers acting as inhibitory complexes of plasmid DNA replication. When carrying a mutation enhancing its amyloidogenesis (A31V), the N-terminal domain (WH1) generates cytosolic amyloid particles that are inheritable within a bacterial lineage. Such amyloids trigger in bacteria a lethal cascade reminiscent to mitochondria impairment in human cells affected by neurodegeneration. To fulfil all the features of a prion-like protein, horizontal (intercellular) transmissibility remains to be demonstrated for RepA-WH1. Since this is experimentally intractable in bacteria, here we transiently expressed in a murine neuroblastoma cell line the soluble, barely cytotoxic RepA-WH1(WT) and assayed its response to co-incubation with in vitro assembled RepA-WH1(A31V) amyloid fibres. In parallel, cells releasing RepA-WH1(A31V) aggregates were co-cultured with human neuroblastoma cells expressing RepA-WH1(WT). Both the assembled fibres and the extracellular RepA-WH1(A31V) aggregates induce, in the cytosol of recipient cells, the formation of cytotoxic amyloid particles. Mass spectrometry analyses of the proteomes of both types of injured cells point to alterations in mitochondria, protein quality triage, signalling and intracellular traffic.Summary blurbThe horizontal, cell-to-cell spread of a bacterial prion-like protein is shown for the first time in mammalian cells. Amyloid cross-aggregation of distinct variants, and their associated toxicities, follow the same trend found in bacteria, underlining the universality of prion biology.
Validation of a high-performance liquid chromatography-tandem mass spectrometry immunopeptidomics assay for the identification of HLA class I ligands suitable for pharmaceutical therapies
Authors: Ghosh Michael , Gauger Marion , Marcu Ana , Nelde Annika , Denk Monika , Schuster Heiko , Rammensee Hans-Georg , Stevanović Stefan 
Published: October 2019

AbstractFor more than two decades naturally presented, human leukocyte antigen (HLA)-restricted peptides (immunopeptidome) have been eluted and sequenced using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Since, identified disease-associated HLA ligands have been characterized and evaluated as potential active substances. Treatments based on HLA-presented peptides have shown promising results in clinical application as personalized T cell-based immunotherapy. Peptide vaccination cocktails are produced as investigational medicinal products under GMP conditions. In order to support clinical trials based on HLA-presented tumor-associated antigens, in this study the sensitive LC-MS/MS HLA class I antigen identification pipeline was fully validated for our technical equipment according to the current US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines.The immunopeptidomes of JY cells with or without spiked-in, isotope labeled peptides, of peripheral blood mononuclear cells of healthy volunteers as well as a chronic lymphocytic leukemia and a bladder cancer sample were reliably identified using a data-dependent acquisition method. As the LC-MS/MS pipeline is used for identification purposes, the validation parameters include accuracy, precision, specificity, limit of detection and robustness.
RNA-spray-mediated silencing ofFusarium graminearum AGOandDCLgenes improve barley disease resistance
Authors: Werner B , Gaffar FY , Schuemann J , Biedenkopf D , Koch A 
Published: October 2019

AbstractOver the last decade, several studies have revealed the enormous potential of RNA-silencing strategies as a potential alternative to conventional pesticides for plant protection. We have previously shown that targeted gene silencing mediated by anin plantaexpression of non-coding inhibitory double-stranded RNAs (dsRNAs) can protect host plants against various diseases with unprecedented efficiency. In addition to the generation of RNA-silencing (RNAi) signalsin planta, plants can be protected from pathogens and pests by spray-applied RNA-based biopesticides. Despite the striking efficiency of RNA-silencing-based technologies holds for agriculture, the molecular mechanisms underlying spray-induced gene silencing (SIGS) strategies are virtually unresolved, a requirement for successful future application in the field. Based on our previous work, we predict that the molecular mechanism of SIGS is controlled by the fungal-silencing machinery. In this study, we used SIGS to compare the silencing efficiencies of computationally-designed versus manually-designed dsRNA constructs targetingARGONAUTEandDICERgenes ofFusarium graminearum(Fg). We found that targeting key components of the fungal RNAi machinery via SIGS could protect barley leaves fromFginfection and that the manual design of dsRNAs resulted in higher gene-silencing efficiencies than the tool-based design. Moreover, our results indicate the possibility of cross-kingdom RNA silencing in theFg-barley interaction, a phenomenon in which sRNAs operate as effector molecules to induce gene silencing between species from different kingdoms, such as a plant host and their interacting pathogens.
Broadband Dynamics Rather than Frequency-Specific Rhythms Underlie Prediction Error in the Primate Auditory Cortex
Authors: Canales-Johnson Andrés , Teixeira Borges Ana Filipa , Komatsu Misako , Fujii Naotaka , Fahrenfort Johannes J. , Miller Kai J. , Noreika Valdas 
Published: October 2019

AbstractDetection of statistical irregularities, measured as a prediction error response, is fundamental to the perceptual monitoring of the environment. We studied whether prediction error response is associated with neural oscillations or asynchronous broadband activity. Electrocorticography (ECoG) was carried out in three male monkeys, who passively listened to the auditory roving oddball stimuli. Local field potentials (LFP) recorded over the auditory cortex underwent spectral principal component analysis, which decoupled broadband and rhythmic components of the LFP signal. We found that the broadband component captured the prediction error response, whereas none of the rhythmic components were associated with statistical irregularities of sounds. The broadband component displayed more stochastic, asymmetrical multifractal properties than the rhythmic components, which revealed more self-similar dynamics. We thus conclude that the prediction error response is captured by neuronal populations generating asynchronous broadband activity, defined by irregular dynamical states which, unlike oscillatory rhythms, appear to enable the neural representation of auditory prediction error response.Significance StatementThis study aimed to examine the contribution of oscillatory and asynchronous components of auditory local field potentials in the generation of prediction error responses to sensory irregularities, as this has not been directly addressed in the previous studies. Here, we show that mismatch negativity – an auditory prediction error response – is driven by the asynchronous broadband component of potentials recorded in the auditory cortex. This finding highlights the importance of non-oscillatory neural processes in the predictive monitoring of the environment. At a more general level, the study demonstrates that stochastic neural processes, which are often disregarded as neural noise, do have a functional role in the processing of sensory information.
Intrinsic dynamics enhance temporal stability of stimulus representation along rodent visual cortical hierarchies
Authors: Piasini Eugenio , Soltuzu Liviu , Muratore Paolo , Caramellino Riccardo , Vinken Kasper , de Beeck Hans Op , Balasubramanian Vijay , Zoccolan Davide 
Published: October 2019

SummaryAlong the ventral stream, cortical representations of brief, static stimuli become gradually more invariant to identity-preserving transformations. In the presence of long, temporally structured dynamic stimuli, higher invariance should imply temporally persistent representations at the top of this functional hierarchy. However, such stimuli could engage adaptive and predictive processes, whose impact on neural coding dynamics is unknown. By probing the rat analogue of the ventral stream with movies, we uncovered a hierarchy of temporal scales, with deeper areas encoding visual information more persistently. Furthermore, the impact of intrinsic dynamics on the stability of stimulus representations gradually grew along the hierarchy. Analysis of a large dataset of recordings from the mouse visual hierarchy yielded similar trends, revealing also their dependence on the behavioral state of the animal. Overall, these findings show that visual representations become progressively more stable along rodent visual processing hierarchies, with an important contribution provided by intrinsic processing.
ER transmembrane protein TMTC3 contributes to O-mannosylation of E-cadherin, Cellular Adherence and Embryonic Gastrulation
Authors: Graham Jill B. , Sunryd Johan C. , Mathavan Ketan , Weir Emma , Larsen Ida Signe Bohse , Halim Adnan , Clausen Henrik , Cousin Hélène , Alfandari Dominque , Hebert Daniel N. 
Published: October 2019

AbstractProtein glycosylation plays essential roles in protein structure, stability and activity such as cell adhesion. The cadherin superfamily of adhesion molecules carry O-linked mannose glycans at conserved sites and it was recently demonstrated that the TMTC1-4 genes contribute to the addition of these O-linked mannoses. Here, biochemical, cell biological and organismal analysis was used to determine that TMTC3 supports the O-mannosylation of E-cadherin, cellular adhesion and embryonic gastrulation. Using genetically engineered cells lacking all four TMTC genes, overexpression of TMTC3 rescued O-linked glycosylation of E-cadherin and cell adherence. The knockdown of the Tmtcs in Xenopus laevis embryos caused a delay in gastrulation that was rescued by the addition of human TMTC3. Mutations in TMTC3 have been linked to neuronal cell migration diseases including Cobblestone lissencephaly. Analysis of TMTC3 mutations associated with Cobblestone lissencephaly found that three of the variants exhibit reduced stability and missence mutations were unable to complement TMTC3 rescue of gastrulation in Xenopus embryo development. Our study demonstrates that TMTC3 regulates O-linked glycosylation and cadherin-mediated adherence, providing insight into its effect on cellular adherence and migration, as well the basis of TMTC3-associated Cobblestone lissencephaly.
Distinguishing Felsenstein zone from Farris zone using neural networks
Authors: Drucks Tamara , Leuchtenberger Alina F. , Burgstaller-Muehlbacher Sebastian , Crotty Stephen M. , Schmidt Heiko A. , von Haeseler Arndt 
Published: October 2019

AbstractMaximum likelihood and maximum parsimony are two key methods for phylogenetic tree reconstruction. Under certain conditions, each of these two methods can perform more or less efficiently than the other. We show that a neural network can efficiently distinguish between four-taxon alignments that were evolved under conditions conducive to long-branch attraction, or long-branch repulsion. The feedback from the neural network can be used to select the most efficient tree reconstruction method yielding increased accuracy, when compared to a rigid choice of reconstruction methods. When applied to the contentious case of Strepsiptera evolution, our method agrees with the current scientific view.
Aβ receptors specifically recognize molecular features displayed by fibril ends and neurotoxic oligomers
Authors: Amin Ladan , Harris David A. 
Published: October 2019

ABSTRACTOligomeric forms of amyloid-β (Aβ) peptide are known to be the primary neurotoxic species in Alzheimer’s disease (AD), but how they interact with neurons to produce their deleterious effects is unclear. Over ten different cell-surface receptors for Aβ have been described, but their molecular interactions with Aβ assemblies and their relative contributions to mediating AD pathology have remained uncertain. In the present work, we have used super-resolution microscopy to directly visualize Aβ-receptor interactions at the nanometer scale. We report that one documented Aβ receptor, the cellular prion protein, PrPC, specifically inhibits the polymerization Aβ fibrils via a unique mechanism in which it binds specifically to the rapidly growing end of each fibril, thereby blocking polarized elongation at that end. PrPC binds neurotoxic oligomers and protofibrils in a similar fashion, suggesting that it may recognize a common, end-specific, structural motif on all of these assemblies. Finally, two other candidate Aβ receptors, FcγRIIb and LilrB2, affect Aβ fibril growth in a manner similar to PrPC. Taken together, our results suggest that neurotoxic signaling by several different receptors may be activated by common molecular interactions with both fibrillar and oligomeric Aβ ligands. Targeting such interactions with small molecules represents an attractive therapeutic strategy for treatment of AD.
A role for keratins in supporting mitochondrial organization and function in skin keratinocytes
Authors: Steen Kaylee , Chen Desu , Wang Fengrong , Chen Song , Kumar Surinder , Lombard David B. , Weigert Roberto , Zieman Abigail G. , Parent Carole A. , Coulombe Pierre A. 
Published: October 2019

AbstractMitochondria fulfill essential roles in ATP production, metabolic regulation, calcium signaling, generation of reactive oxygen species (ROS) and additional determinants of cellular health. Recent studies have highlighted a role for mitochondria during cell differentiation, including in skin epidermis. The observation of oxidative stress in keratinocytes fromKrt16null mouse skin, a model for pachyonychia congenita (PC)-associated palmoplantar keratoderma, prompted us to examine the role of Keratin (K) 16 protein and its partner K6 in regulating the structure and function of mitochondria. Electron microscopy revealed major anomalies in mitochondrial ultrastructure in late stage, E18.5,Krt6a/Krt6bnull embryonic mouse skin. Follow-up studies utilizing biochemical, metabolic, and live imaging readouts showed that, relative to controls, skin keratinocytes null forKrt6a/Krt6borKrt16exhibit elevated ROS, reduced mitochondrial respiration, intracellular distribution differences and altered movement of mitochondria within the cell. These findings highlight a novel role for K6 and K16 in regulating mitochondrial morphology, dynamics and function and shed new light on the causes of oxidative stress observed in PC and related keratin-based skin disorders.
Firing Rate-dependent Phase Responses of Purkinje Cells Support Transient Oscillations
Authors: Zang Yunliang , Hong Sungho , De Schutter Erik 
Published: October 2019

AbstractBoth spike rate and timing can transmit information in the brain. Phase response curves (PRCs) quantify how a neuron transforms input to output by spike timing. They exhibit strong firing-rate adaptation, but its mechanism and relevance for network output are poorly understood. Using our Purkinje cell (PC) model we demonstrate that the rate adaptation is caused by rate-dependent subthreshold membrane potentials efficiently regulating the activation of Na+ channels. Then we use a realistic PC network model to examine how rate-dependent responses synchronize spikes in the scenario of reciprocal inhibition-caused high-frequency oscillations. The changes in PRC cause oscillations and spike correlations only at high firing rates. The causal role of the PRC is confirmed using a simpler coupled oscillator network model. This mechanism enables transient oscillations between fast-spiking neurons that thereby form PC assemblies. Our work demonstrates that rate adaptation of PRCs can spatio-temporally organize the PC input to cerebellar nuclei.