bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Cochlear Length Using Cone Beam Computed Tomography in Adults With Cochlear Implants
Authors: Alnafjan Fadwa F. , Allan Stuart M. , McMahon Catherine M. , da Cruz Melville J. 
Published: August 2018

Developing a clinically viable technique for measuring cochlear length could enhance future electrode design of cochlear implants and surgical skills to improve clinical outcomes. While computed tomography (CT) has been used, metal artifact and the exposure to higher levels of radiation limits its use. More recently, cone beam CT (CBCT) has been used to assess the integrity of the implant array in situ, exposing implantees to lower levels of radiation while retaining image quality. The current study aims to develop a technique for measuring cochlear length in implanted adults, using CBCT images combined with known dimensions of implant arrays and lengths of cochlear structures from cadaveric human temporal bones.

Study Design:
One hundred CBCT temporal bone images of ears implanted with Cochlear straight or perimodiolar arrays were reviewed by two independent examiners.

Results:
Outer-wall length, based on the position of the straight array within the cochlea and the reported average length of the organ of Corti, was 27.44 to 35.91 mm (mean = 32.24 mm). Inner-wall length, based on the position of the perimodiolar array and the reported average length of the spiral ganglion, ranged from 17.8 to 22.24 mm (mean = 19.43 mm).

Conclusion:
A novel method for calculating outer- and inner-wall cochlear length using CBCT images has been developed which is feasible in clinical settings.
Death and Dying in the ICU: Personal Reflection of 30 Years’ Experience
Authors: Butt Warwick W. 
Published: August 2018

Objective:
To describe individual perspective over ~30 years in a mixed Cardiac and General ICU, which includes the State Trauma Center, National Cardiac Transplant and Complex Cardiac Center, Extracorporeal Membrane Oxygenation Center, Home Ventilation Program, and the major PICU for 6 million people.

Data Sources:
Personal experience and reflection, complemented by published local data.

Study Selection:
Illustrative publications of local other data.

Data Synthesis:
Narrative, experiential reflection.

Conclusions:
I have agreed to palliative care in many patients of diverse religious, social, and cultural beliefs while providing long-term ICU care to other patients with similar illnesses and prognosis. This can occur when family meetings allow honest and direct conversation with respect for differences; as a clinician, I listen to a family and understand their perspectives and together develop a clear and agreed plan.
Investigations After Death in Children
Authors: Bohn Desmond , Chiasson David , Huyer Dirk 
Published: August 2018

Objectives:
To discuss the role of investigations after death in children as part of a supplement on “Death and Dying in the PICU.”

Data Sources:
Literature review, personal experience, and expert opinion.

Data Selection:
Not applicable.

Data Extraction:
Moderated by three experts on investigations after death in children.

Data Synthesis:
Not relevant.

Conclusions:
A multidisciplinary cliniciopathologic conference is important after the death of a child in order to help bring closure to the family and to attempt to address any concerns they may have about the care. It is also an important part of the quality of care process for a tertiary care institution and provides an unique opportunity for ongoing medical education. The model of a multidisciplinary cliniciopathologic conference used by the Ontario Coroner’s Office to investigate sudden and unexpected deaths in children under 5 years old, which has been functioning for over 30 years, is described. Reports from this Pediatric Death Review Committee have been influential in improving the care of children in the province of Ontario.
Nerve and skin biopsy in neuropathies
Authors: Sommer Claudia 
Published: August 2018

Purpose of review
To give an overview of recent data on the use of nerve and skin biopsy as a diagnostic tool in neuropathies.

Recent findings
Axonal damage in a biopsy from a patient with chronic inflammatory demyelinating polyradiculoneuropathy may point to the presence of autoantibodies to paranodal proteins. In nonsystemic vasculitis of the peripheral nervous system, nerve biopsy is still the only means to make a definite diagnosis. Increased autophagy has been found in idiopathic neuropathy and may also be a common final pathway in various types of neuropathy. Nerve biopsy has unexpectedly revealed familial amyloid neuropathy in a number of cases that were taken for idiopathic, for Charcot-Marie-Tooth disease, or for chronic inflammatory demyelinating polyradiculoneuropathy. Skin biopsy can differentiate between length-dependent and non-length-dependent small fiber neuropathy, which aids in the etiological differential diagnosis. It can also be used to identify small fiber involvement in mixed neuropathies and for follow-up studies.

Summary
Nerve biopsy is still the gold standard for the diagnosis of peripheral nerve vasculitis. In other indications, sural or superficial peroneal nerve biopsies are less frequently done, because less invasive methods have become available. Modern imaging methods allow localization of nerve damage, such that targeted fascicular biopsies can be done. Immunofluorescence staining of teased nerve fibers has contributed to the understanding of the pathophysiology of inflammatory neuropathies. Skin biopsy has become a routine method to diagnose small fiber neuropathy.
Machine learning and genomics: precision medicine versus patient privacy
Authors: Azencott C.-A. 
Published: August 2018

Machine learning can have a major societal impact in computational biology applications. In particular, it plays a central role in the development of precision medicine, whereby treatment is tailored to the clinical or genetic features of the patient. However, these advances require collecting and sharing among researchers large amounts of genomic data, which generates much concern about privacy. Researchers, study participants and governing bodies should be aware of the ways in which the privacy of participants might be compromised, as well as of the large body of research on technical solutions to these issues. We review how breaches in patient privacy can occur, present recent developments in computational data protection and discuss how they can be combined with legal and ethical perspectives to provide secure frameworks for genomic data sharing.This article is part of a discussion meeting issue ‘The growing ubiquity of algorithms in society: implications, impacts and innovations’.
NHX-type Na+(K+)/H+ antiporter activity is required for endomembrane trafficking and ion homeostasis in Arabidopsis thaliana
Authors: Dragwidge Jonathan Michael , Scholl Stefan , Schumacher Karin , Gendall Anthony Richard 
Published: August 2018

AbstractThe regulation of ion and pH homeostasis of endomembrane organelles is critical for functional protein trafficking, sorting and modification in eukaryotic cells. pH homeostasis is maintained through the activity of vacuolar H+-ATPases (V-ATPases) pumping protons (H+) into the endomembrane lumen, and counter-action by cation/proton exchangers such as the NHX family of Na+(K+)/H+ exchangers. In plants, disturbing V-ATPase activity at the trans-Golgi network/early endosome (TGN/EE) impairs secretory and endocytic trafficking. However, it is unclear if the endosomal NHX-type antiporters NHX5 and NHX6 play functionally similar roles in endomembrane trafficking through maintaining ion and pH homeostasis. Here we show through genetic, pharmacological, and live-cell imaging approaches that double knockout of endosomal isoforms NHX5 and NHX6 results in impairment of endosome motility, protein recycling at the TGN/EE, but not in the secretion of integral membrane proteins. Furthermore, we report that nhx5 nhx6 mutants are partially insensitive to osmotic swelling of TGN/EE induced by the monovalent cation ionophore monensin. Similarly, nhx5 nhx6 cells are unresponsive to late endosomal swelling by the phosphatidylinositol 3/4-kinase inhibitor wortmannin, demonstrating that NHX5 and NHX6 are required for maintaining endosomal cation balance. Lastly, we report that the distal region of the cytosolic tail of NHX6 is required for mediating NHX6 localisation to late endosomes, but does not appear to be essential for NHX6 function.
A strain of an emerging Indian pathotype of Xanthomonas oryzae pv. oryzae defeats the rice bacterial blight resistance gene xa13 without inducing a clade III SWEET gene and is nearly identical to a recent Thai isolate
Authors: Carpenter Sara C. D. , Mishra Prashant , Ghoshal Chandrika , Dash Prasanta , Wang Li , Midha Samriti , Laha Gouri S. , Lore Jagjeet S , Kositratana Wichai , Singh Nagendra K. , Singh Kuldeep , Patil Prabhu B. , Oliva Ricardo , Patarapuwadol Sujin , Bogdanove Adam J , Rai Rhitu 
Published: August 2018

AbstractThe rice bacterial blight pathogen Xanthomonas oryzae pv. oryzae (Xoo) injects transcription activator-like effectors (TALEs) that bind and activate host ‘susceptibility’ (S) genes important for disease. Clade III SWEET genes are major S genes for bacterial blight. The resistance genes xa5, which reduces TALE activity generally, and xa13, a SWEET11 allele not recognized by the cognate TALE, have been effectively deployed. However, strains that defeat both resistance genes individually were recently reported in India and Thailand. To gain insight into the mechanism(s), we completely sequenced the genome of one such strain from each country and examined the encoded TALEs. Strikingly, the two strains are clones, sharing nearly identical TALE repertoires, including a TALE known to activate SWEET11 strongly enough to be effective even when diminished by xa5. We next investigated SWEET gene induction by the Indian strain. The Indian strain induced no clade III SWEET in plants harbouring xa13, indicating a pathogen adaptation that relieves dependence on these genes for susceptibility. The findings open a door to mechanistic understanding of the role SWEET genes play in susceptibility and illustrate the importance of complete genome sequence-based monitoring of Xoo populations in developing varieties with effective disease resistance.
An automated, high-throughput image analysis pipeline enables genetic studies of shoot and root morphology in carrot (Daucus carota L.)
Authors: Turner Sarah D. , Ellison Shelby L. , Senalik Douglas A. , Simon Philipp W. , Spalding Edgar P. , Miller Nathan D. 
Published: August 2018

AbstractCarrot is a globally important crop, yet efficient and accurate methods for quantifying its most important agronomic traits are lacking. To address this problem, we developed an automated analysis platform that extracts components of size and shape for carrot shoots and roots, which are necessary to advance carrot breeding and genetics. This method reliably measured variation in shoot size and shape, leaf number, petiole length, and petiole width as evidenced by high correlations with hundreds of manual measurements. Similarly, root length and biomass were accurately measured from the images. This platform quantified shoot and root shapes in terms of principal components, which do not have traditional, manually-measurable equivalents. We applied the pipeline in a study of a six-parent diallel population and an F2 mapping population consisting of 316 individuals. We found high levels of repeatability within a growing environment, with low to moderate repeatability across environments. We also observed co-localization of quantitative trait loci for shoot and root characteristics on chromosomes 1, 2, and 7, suggesting these traits are controlled by genetic linkage and/or pleiotropy. By increasing the number of individuals and phenotypes that can be reliably quantified, the development of a high-throughput image analysis pipeline to measure carrot shoot and root morphology will expand the scope and scale of breeding and genetic studies.
Bayesian Nonparametric Models Characterize Instantaneous Strategies in a Competitive Dynamic Game
Authors: McDonald Kelsey R. , Broderick William F. , Huettel Scott A. , Pearson John M. 
Published: August 2018

AbstractPrevious approaches to investigating strategic social interaction in game theory have predominantly used games with clearly-defined turns and limited choices. However, most real-world social behaviors involve dynamic, coevolving decisions by interacting agents, which pose challenges for creating tractable models of behavior. Here, using a competitive game in which human participants control the dynamics of an on-screen avatar against either another human or a computer opponent, we show that it is possible to quantify the dynamic coupling between agents using nonparametric models. We use Gaussian Processes to model the joint distributions of players’ actions and identities (human or computer) as a function of game state. Borrowing from a reinforcement learning framework, we successfully approximated both the policy and the value functions used by each human player in this competitive context. This approach offers a natural set of metrics for facilitating analysis at multiple timescales and suggests new classes of tractable paradigms for assessing human behavior.
Monte-Carlo Diffusion-Enhanced Photon Inference: Distance Distributions And Conformational Dynamics In Single-Molecule FRET
Authors: Ingargiola Antonino , Weiss Shimon , Lerner Eitan 
Published: August 2018

AbstractSingle-molecule Förster Resonance Energy Transfer (smFRET) is utilized to study the structure and dynamics of many bio-molecules, such as proteins, DNA and their various complexes. The structural assessment is based on the well-known Förster relationship between the measured efficiency of energy transfer between a donor (D) and an acceptor (A) dye and the distance between them. Classical smFRET analysis methods called photon distribution analysis (PDA) take into account photon shot-noise, D-A distance distribution and, more recently, interconversion between states in order to extract accurate distance information. It is known that rapid D-A distance fluctuations on the order of the D lifetime (or shorter) can increase the measured mean FRET efficiency and thus decrease the estimated D-A distance. Nonetheless, this effect has been so far neglected in smFRET experiments, potentially leading to biases in estimated distances.Here we introduce a PDA approach dubbed Monte-Carlo-diffusion-enhanced photon inference (MC-DEPI). MC-DEPI recolor detected photons of smFRET experiments taking into account dynamics of D-A distance fluctuations, multiple interconverting states and photo-blinking. Using this approach, we show how different underlying conditions may yield identical FRET histograms and how the additional information from fluorescence decays helps distinguishing between the different conditions. We also introduce a machine learning fitting approach for retrieving the D-A distance distribution, decoupled from the above-mentioned effects. We show that distance interpretation of smFRET experiments of even the simplest dsDNA is nontrivial and requires decoupling the effects of rapid D-A distance fluctuations on FRET in order to avoid systematic biases in the estimation of the D-A distance distribution.
Why panmictic bacteria are rare
Authors: Yang Chao , Cui Yujun , Didelot Xavier , Yang Ruifu , Falush Daniel 
Published: August 2018

AbstractBackgroundBacteria typically have more structured populations than higher eukaryotes, but this difference is surprising given high recombination rates, enormous population sizes and effective geographical dispersal in many bacterial species.ResultsWe estimated the recombination scaled effective population sizeNerin 21 bacterial species and find that it does not correlate with synonymous nucleotide diversity as would be expected under neutral models of evolution. Only two species have estimates substantially over 100, consistent with approximate panmixia, namelyHelicobacter pyloriandVibrio parahaemolyticus. Both species are far from demographic equilibrium, with diversity predicted to increase more than 30 fold inV. parahaemolyticusif the current value ofNerwere maintained, to values much higher than found in any species. We propose that panmixia is unstable in bacteria, and that persistent environmental species are likely to evolve barriers to genetic exchange, which act to prevent a continuous increase in diversity by enhancing genetic drift.ConclusionsOur results highlight the dynamic nature of bacterial population structures and imply that overall diversity levels found within a species are poor indicators of its size.
Mapping the human kinome in response to DNA damage
Authors: Owusu Michel , Bannauer Peter , Mourikis Athanasios , Jones Alistair , Silva Joana Ferreira da , Caldera Michael , Wiedner Marc , Lardeau Charles-Hugues , Menche Jörg , Kubicek Stefan , Ciccarelli Francesca , Loizou Joanna I. 
Published: August 2018

SummaryWe provide a catalog for the effects of the human kinome on cell survival in response to DNA damaging agents, selected to cover all major DNA repair pathways. By treating 313 kinase-deficient cell lines with ten diverse DNA damaging agents, including seven commonly used chemotherapeutics, we were able to identify kinase specific vulnerabilities and resistances. In order to identify novel synthetic lethal interactions, we investigate the cellular response to carmustine for 25 cell lines, by establishing a phenotypic FACS assay designed to mechanistically investigate and validate gene-drug interactions. We show apoptosis, cell cycle, DNA damage and proliferation after alkylation or crosslink-induced damage for selected cell lines and rescue the cellular sensitivity of DYRK4, EPHB6, MARK3, PNCK as a proof of principle for our study. Our data suggest that some cancers with inactivated DYRK4, EPHB6, MARK3 or PNCK gene could be particularly vulnerable to treatment by alkylating chemotherapeutic agents carmustine or temozolomide.
Spatiotemporal ontogeny of brain wiring
Authors: Goulas Alexandros , Betzel Richard F. , Hilgetag Claus C. 
Published: August 2018

AbstractThe wiring of the brain provides the anatomical skeleton for cognition and behavior. Connections among brain regions have a diverse and characteristic strength. This strength heterogeneity is captured by the wiring cost and homophily principles. Moreover, brains have a characteristic global network topology, including modularity and short path lengths. However, the mechanisms underlying the inter-regional wiring principles and global network topology of brains are unknown. Here, we address this issue by modeling the ontogeny of brain connectomes. We demonstrate that spatially embedded and heterochronous neurogenetic gradients, without the need of axonal-guidance molecules or activity-dependent plasticity, can reconstruct the wiring principles and shape the global network topology observed in adult brain connectomes. Thus, two fundamental dimensions, that is, space and time, are key components of a plausible neurodevelopmental mechanism with a universal scope, encompassing vertebrate and invertebrate brains.
Assessment of Functional Connectome Construction Strategies in Neurodegeneration
Authors: Vanhoecke J , McColgan P , Razi A , Gregory S , Seunarine K , Durr A , Roos R , Leavitt B , Scahill RI , Clark C , Tabrizi SJ , Rees G ,   Track On-HD Investigators
Published: August 2018

AbstractConnectomics can be used to investigate functional brain networks in neurodegenerative diseases including Huntington’s disease (HD). In this developing field, different connectome construction strategies have emerged in parallel. However, there is a need to understand the influences of different strategies on subsequent analyses when constructing a connectome. This study systematically compares connectome construction strategies based on their biological relevance to functional networks in neurodegeneration.We asked which functional connectome construction strategy was best able to discriminate HD gene carriers from healthy controls, and how such a strategy affected modular organization of the network. The major factors compared were principal component-based correction versus wavelet decomposition for physiological noise correction, the type of parcellation atlas (functional, structural and multi-modal), weighted versus binarized networks, and unthresholded versus proportionally thresholded networks. We found that principal component-based correction generated the most discriminatory connectomes, while binarization and proportional thresholding did not increase discrimination between HD gene carriers and healthy controls. When a functional parcellation atlas was used, the highest discrimination rates were obtained. We observed that the group differences in modular organization of the functional connectome were greatly affected by binarization and thresholding, showing no consistent pattern of modularity.This study suggests that functional connectome construction strategies using principal component-based correction and weighted unthresholded connectivity matrices may outperform other strategies.
Bile Acid Biosynthesis Avoiding Cholesterol
Authors: Griffiths William J. , Abdel-Khalik Jonas , Crick Peter J. , Yutuc Eylan , Ogundare Michael , Bigger Brian W. , Morris Andrew A. , Shackleton Cedric H. , Clayton Peter T. , Iida Takashi , Sircar Ria , Marschall Hanns-Ulrich , Sjövall Jan , Björkhem Ingemar , Rohatgi Rajat , Wang Yuqin 
Published: August 2018

AbstractBile acids are the end products of cholesterol metabolism secreted into bile. They are essential for the absorption of lipids and lipid soluble compounds from the intestine. Here we have investigated the bile acid content of plasma and urine from patients with a defect in cholesterol biosynthesis, i.e. Smith-Lemli-Opitz syndrome (SLOS), resulting in elevated levels of 7-dehydrocholesterol (7-DHC), an immediate precursor of cholesterol. Using liquid chromatography – mass spectrometry (LC-MS) we have identified a novel pathway of bile acid biosynthesis in SLOS avoiding cholesterol starting with 7-DHC. This pathway also proceeds to a minor extent in healthy individuals. Monitoring of the pathway products could provide a rapid diagnostic for SLOS while elevated levels of pathway intermediates could be responsible for some of the features of the disease. Importantly, intermediates in the pathway are modulators of the activity of Smoothened, an oncoprotein that mediates Hedgehog signalling during embryogenesis and regeneration of postembryonic tissue.