bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maximising information on smell, quantitative motor impairment and probable REM-sleep behaviour disorder in the prediction of Parkinson’s disease
Authors: Bestwick Jonathan P. , Auger Stephen D. , Schrag Anette E. , Grosset Donald G , Kanavou Sofia , Giovannoni Gavin , Lees Andrew J. , Cuzick Jack , Noyce Alastair J. 
Published: March 2020

ABSTRACTBackgroundHyposmia, motor impairment and probable REM-sleep behaviour disorder (RBD) are markers for Parkinson’s disease (PD). Proposed PD risk prediction models have dichotomised test results and applied likelihood ratios (LRs) to scores above and below cut-offs. We investigate whether LRs for specific test values could enhance prediction models.MethodsSmell and probable RBD data for PD patients were taken from the Tracking Parkinson’s study (n=1046). For motor impairment previously published data were supplemented (n=87). PREDICT-PD pilot study participants were the controls. Smell, motor impairment and RBD were assessed using the University of Pennsylvania Smell Identification Test (UPSIT), the Bradykinesia-Akinesia Incoordination (BRAIN) test and the REM sleep behaviour disorder Screening Questionnaire (RBDSQ). UPSIT and RBDSQ data were analysed using logistic regression to determine which items were predictive of PD, or using total scores. Gaussian distributions were fitted to BRAIN test scores. LRs were calculated from logistic regression models or from score distributions. False-positive rates (FPRs) for specified detection rates (DRs) were calculated.ResultsLogistic regression modelling yielded a greater range of LRs. 16 odours were associated with PD; LRs ranged from 0.005-5511. 6 RBDSQ questions were associated with PD; LRs ranged from from 0.34-69. BRAIN test LRs ranged from 0.16-1311. For a 70% DR the FPR for the 16 odours was 2.4%, for 50% DRs, the BRAIN test FPR was 6.6% and 12.2% for the RBDSQ.ConclusionsMaximising information on PD markers can potentially improve the ability of algorithms to detect PD by generating LRs with a larger range of values than using dichotomised results.
Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside-Wuhan patients, China
Authors: Qiu Chengfeng , Xiao Qian , Liao Xin , Deng Ziwei , Liu Huiwen , Shu Yuanlu , Zhou Dinghui , Deng Ye , Wang Hongqiang , Zhao Xiang , Zhou Jianliang , Wang Jin , Shi Zhihua , Long Da 
Published: March 2020

AbstractBackgroundCases with coronavirus disease 2019 (COVID-19) emigrated from Wuhan escalated the risk of spreading in other cities. This report focused on the outside-Wuhan patients to assess the transmission and clinical characteristics of this illness.MethodsContact investigation was conducted on each patient who admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from Jan 22, 2020 to Feb 12, 2020. Demographic, clinical, laboratory and radiological characteristics, medication therapy and outcomes were collected and analyzed. Patients were confirmed by PCR test.ResultsOf the 104 patients, 48 (46.15%) were imported cases and 56 (53.85%) were indigenous cases; 93 (89.42%) had a definite contact history with infections. Family clusters were the major body of patients. Transmission along the chain of 3 “generations” was observed. Mean age was 43 (rang, 8-84) years (including 3 children) and 49 (47.12%) were male. Most patients had typical symptoms, 5 asymptomatic infections were found and 2 of them infected their relatives. The median incubation period was 6 (rang, 1-32) days, of 8 patients ranged from 18 to 32 days. Just 9 of 16 severe patients required ICU care. Until Feb 12, 2020, 40 (38.46%) discharged and 1 (0.96%) died. For the antiviral treatment, 80 (76.92%) patients received traditional Chinese medicine therapy.ConclusionsFamily but not community transmission occupied the main body of infections in the two centers. Asymptomatic transmission demonstrated here warned us that it may bring more risk to the spread of COVID-19. The incubation period of 8 patients exceeded 14 days.
Nanopore target sequencing for accurate and comprehensive detection of SARS-CoV-2 and other respiratory viruses
Authors: Wang Ming , Fu Aisi , Hu Ben , Tong Yongqing , Liu Ran , Gu Jiashuang , Liu Jianghao , Jiang Wen , Shen Gaigai , Zhao Wanxu , Men Dong , Deng Zixin , Yu Lilei , Li Yan , Liu Tiangang 
Published: March 2020

AbstractThe ongoing novel coronavirus pneumonia COVID-19 outbreak in Wuhan, China, has engendered numerous cases of infection and death. COVID-19 diagnosis relies upon nucleic acid detection; however, current recommended methods exhibit high false-negative rates, low sensitivity, and cannot identify other respiratory virus infections, thereby resulting patient misdiagnosis and impeding epidemic containment. Combining the advantages of target amplification and long-read, real-time nanopore sequencing, we developed nanopore target sequencing (NTS) to detect SARS- CoV-2 and other respiratory viruses simultaneously within 6–10 h. Parallel testing with approved qPCR kits of SARS-CoV-2 and NTS using 61 nucleic acid samples from suspected COVID-19 cases confirmed that NTS identified more infected patients as positive, and could also monitor for mutated nucleic acid sequence or other respiratory virus infection in the test sample. NTS is thus suitable for contemporary COVID-19 diagnosis; moreover, this platform can be further extended for diagnosing other viruses or pathogens.
Pinna-Imitating Microphone Directionality Improves Sound Localization and Discrimination in Bilateral Cochlear Implant Users
Authors: Fischer Tim , Schmid Christoph , Kompis Martin , Mantokoudis Georgios , Caversaccio Marco , Wimmer Wilhelm 
Published: March 2020

AbstractObjectivesTo compare the sound-source localization, discrimination and tracking performance of bilateral cochlear implant users with omnidirectional (OMNI) and pinna-imitating (PI) microphone directionality modes.DesignTwelve experienced bilateral cochlear implant users participated in the study. Their audio processors were fitted with two different programs featuring either the OMNI or PI mode. Each subject performed static and dynamic sound field spatial hearing tests in the horizontal plane. The static tests consisted of an absolute sound localization test and a minimum audible angle (MAA) test, which was measured at 8 azimuth directions. Dynamic sound tracking ability was evaluated by the subject correctly indicating the direction of a moving stimulus along two circular paths around the subject.ResultsPI mode led to statistically significant sound localization and discrimination improvements. For static sound localization, the greatest benefit was a reduction in the number of front-back confusions. The front-back confusion rate was reduced from 47% with OMNI mode to 35% with PI mode (p = 0.03). The ability to discriminate sound sources at the sides was only possible with PI mode. The MAA value for the sides decreased from a 75.5 to a 37.7-degree angle when PI mode was used (p < 0.001). Furthermore, a non-significant trend towards an improvement in the ability to track sound sources was observed for both trajectories tested (p = 0.34 and p = 0.27).ConclusionsOur results demonstrate that PI mode can lead to improved spatial hearing performance in bilateral cochlear implant users, mainly as a consequence of improved front-back discrimination with PI mode.
AI boosted molecular MRI for apoptosis detection in oncolytic virotherapy
Authors: Perlman Or , Ito Hirotaka , Herz Kai , Shono Naoyuki , Nakashima Hiroshi , Zaiss Moritz , Chiocca E. Antonio , Cohen Ouri , Rosen Matthew S. , Farrar Christian T. 
Published: March 2020

AbstractOncolytic virotherapy is a promising treatment for high mortality cancers1. Non-invasive imaging of the underlying molecular processes is an essential tool for therapy optimization and assessment of viral spread, innate immunity, and therapeutic response2, 3. However, previous methods for imaging oncolytic viruses did not correlate with late viral activity4or had poor sensitivity and specificity5. Similarly, methods developed to image treatment response, such as apoptosis, proved to be slow, nonspecific, or require the use of radioactive or metal-based contrast agents6–8. To date, no method has been widely adopted for clinical use. We describe here a new method for fast magnetic resonance molecular imaging with quantitative proton chemical-exchange specificity to monitor oncolytic virotherapy treatment response. A deep neural network enabled the computation of quantitative biomarker maps of protein and lipid/macromolecule concentrations as well as intracellular pH in a glioblastoma multiforme mouse brain tumor model. Early detection of apoptotic response to oncolytic virotherapy, characterized by decreased cytosolic pH and protein synthesis, was observed in agreement with histology. Clinical translation was demonstrated in a normal human subject, yielding molecular parameters in good agreement with literature values9. The developed method is directly applicable to a wide range of pathologies, including stroke10, cancer11–13, and neurological disorders14, 15.
Optimization of psoriasis – like mouse models: A comparative study
Authors: Karamani Christina , Antoniadou Ivi Theodosia , Dimou Aikaterini , Andreou Evgenia , Kostakis Georgios , Sideri Asimina , Vitsos Andreas , Gkavanozi Athina , Sfiniadakis Ioannis , Skaltsa Helen , Papaioannou Georgios Theodoros , Maibach Howard , Rallis Michael 
Published: March 2020

AbstractPsoriasis, a common chronic, autoimmune, inflammatory, relapsing disease should benefit from reliable and human relevant animal models in order to pre-clinically test drugs and approach their mechanism of action. Due to ease of use, convenience and low cost, imiquimod (IMQ) induced psoriasis-like model is widely utilized; however, are all mouse strains equivalent, is the hairless mouse utilizable and can the imiquimod model be further optimized? Under similar experimental conditions, common mouse strains (BALB/c, C57BL/6J, ApoE) and a new hairless strain (ApoE/SKH-hr2) as well as several inducers (IMQ, IMQ + Acetic Acid (AcOH) topical and IMQ +AcOH systemic) were compared by clinical, histopathological, biophysical and locomotor activity assessment. Results showed that BALB/c mice yielded optimal psoriasis-like phenotype with IMQ+AcOH topical treatment, C57BL/6J moderate, ApoE mild, while the ApoE/SKH-hr2 mice due to Munro abscess absence in histopathology analysis left doubts about the psoriasis-like acquisition. The locomotor activity of BALB/c mice treated with IMQ, IMQ+AcOH topically and IMQ+AcOH systemically, showed with all treatments, a decreased covered distance and rearing and an increased immobility. In conclusion, BALB/c appears an optimal psoriasis-like model when utilizing IMQ+AcOH topical application.
An Endocytic Capture Model for Skeletal Muscle T-tubule Formation
Authors: Hall Thomas E , Martel Nick , Ariotti Nicholas , Xiong Zherui , Lo Harriet P , Ferguson Charles , Rae James , Lim Ye-Wheen , Parton Robert G 
Published: March 2020

AbstractThe skeletal muscle T-tubule is a specialized membrane domain essential for coordinated muscle contraction that shows dysmorphology in a number of genetically inherited muscle diseases. However, in the absence of genetically tractable systems the mechanisms involved in T-tubule formation are unknown. Here, we have used the optically transparent and genetically tractable zebrafish system to probe T-tubule developmentin vivo. By combining live imaging with three-dimensional electron microscopy we derived a four-dimensional quantitative model for T-tubule formation. To elucidate the mechanisms involved in T-tubule formationin vivowe developed a quantitative screen for proteins that associate with and modulate early T-tubule formation including an overexpression screen of the entire zebrafish Rab protein family. We propose a new endocytic capture model involving i) formation of dynamic endocytic tubules at transient nucleation sites on the sarcolemma ii) stabilization by myofibrils/sarcoplasmic reticulum and iii) delivery of membrane from the recycling endosome and Golgi complex.
A comprehensive proteomic SWATH-MS workflow for profiling blood extracellular vesicles: a new avenue for glioma tumour surveillance
Authors: Hallal Susannah , Azimi Ali , Wei Heng , Ho Nicholas , Lee Maggie , Sim Hao-Wen , Sy Joanne , Shivalingam Brindha , Buckland Michael E. , Kaufman Kimberley L. 
Published: March 2020

AbstractThere is a real need for biomarkers that can indicate glioma disease burden and inform clinical management, particularly in the recurrent glioblastoma (GBM; grade IV glioma) setting where treatment-associated brain changes can confound current and expensive tumour surveillance methods. In this regard, extracellular vesicles (EVs; 30-1000 nm membranous particles) hold major promise as robust tumour biomarkers. GBM-EVs encapsulate molecules that reflect the identity and molecular state of their cell-of-origin and cross the blood-brain-barrier into the periphery where they are readily accessible. Despite the suitability of circulating-EVs for GBM biomarker discovery, sample complexity has hindered comprehensive quantitative proteomic studies. Here, sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used in conjunction with a targeted data extraction strategy to comprehensively profile circulating-EVs isolated from plasma. Plasma-EVs sourced from pre-operative glioma II-IV patients (n=41) and controls (n=11) were sequenced by SWATH-MS, and the identities and absolute quantities of the proteins were extracted by aligning the SWATH-MS data against a custom glioma spectral library comprised of 8662 high confidence protein species. Overall, 4054 plasma-EV proteins were quantified across the cohorts, and putative circulating-EV biomarker proteins identified (adjustedp-value<0.05) included previously reported GBM-EV proteins identifiedin vitroand in neurosurgical aspirates. Principle component analyses showed that plasma-EV protein profiles clustered according to glioma subtype and WHO-grade, and plasma-EV proteins reflected the extent of glioma aggression. Using SWATH-MS, we describe the most comprehensive proteomic plasma-EV profiles for glioma and highlight the promise of this approach as an accurate and sensitive tumour monitoring method. Objective blood-based measurements of glioma tumour activity will support the implementation of next-generation, patient-centred therapies and are ideal surrogate endpoints for recurrent progression that would allow clinical trial protocols to be more dynamic and adapt to the individual patient and their cancer.
RPG: A low-cost, open-source, high-performance solution for displaying visual stimuli
Authors: Imbriotis Vivian , Ranson Adam , Connelly William M 
Published: March 2020

AbstractThe development of new high throughput approaches for neuroscience such as high-density silicon probes and 2-photon imaging have led to a renaissance in visual neuroscience. However, generating the stimuli needed to evoke activity in the visual system still represents a non-negligible difficulty for experimentalists. While several widely used software toolkits exist to deliver such stimuli, they all suffer from some shortcomings. Primarily, the hardware needed to effectively display such stimuli comes at a significant financial cost, and secondly, triggering and/or timing the stimuli such that it can be accurately synchronized with other devices requires the use of legacy hardware, further hardware, or bespoke solutions.Here we present RPG, a Python package written for the Raspberry Pi, which overcomes these issues. Specifically, the Raspberry Pi is a low-cost, credit card sized computer with general purpose input/output pins, allowing RPG to be triggered to deliver stimuli and to provide real-time feedback on stimulus timing. RPG delivers stimuli at >60 frames per second and the feedback of frame timings is accurate to 10s of microseconds.We provide a simple to use Python interface that is capable of generating drifting sine wave gratings, Gabor patches and displaying raw images/video.
Axial Elongation of Caudalized Human Organoids Mimics Neural Tube Development
Authors: Libby ARG , Joy DA , Elder NH , Bulger EA , Krakora MZ , Gaylord EA , Mendoza-Camacho F , Butts JC , McDevitt TC 
Published: March 2020

AbstractAxial elongation of the neural tube is critical during mammalian embryogenesis to establish the anterior-posterior body axis1, but this process is difficult to interrogate directly because it occurs post-implantation2,3. Here we report an organoid model of neural tube extension by caudalized human pluripotent stem cell (hPSC) aggregates that recapitulates the morphologic and temporal gene expression patterns of neural tube development. Axially extending organoids consisting largely of longitudinally elongated neuroepithelial compartments also contained TBXT(+)SOX2(+) neuromesodermal progenitors, PAX6(+)nestin(+) neural progenitor populations, and MEOX1(+) paraxial mesoderm populations. Wnt agonism stimulated singular axial extensions in a dose-dependent manner, and elongated organoids displayed regionalized rostral-caudal HOX gene expression, with spatially distinct hindbrain (HOXB1) expression from brachial (HOXC6) and thoracic (HOXB9) regions. CRISPR-interference-mediated silencing of the TBXT, a downstream Wnt target, increased neuroepithelial compartmentalization and resulted in multiple extensions per aggregate. Further, knock-down of BMP inhibitors, Noggin and Chordin, induced elongation phenotypes that mimicked murine knockout models. These results indicate the potent morphogenic capacity of caudalized hPSC organoids to undergo axial elongation in a manner that can be used to dissect the cellular organization and patterning decisions that dictate early nervous system development in humans.
Hedgehog produced by the Drosophila wing imaginal disc induces distinct expression responses in three target tissues
Authors: Hatori Ryo , Kornberg Thomas B. 
Published: March 2020

AbstractHedgehog (Hh) is an evolutionarily conserved signaling protein that has essential roles in animal development and homeostasis. We investigated Hh signaling in the region of the Drosophila wing imaginal disc that produces Hh and is near the tracheal air sac primordium (ASP) and myoblasts. Hh distributes in concentration gradients in the wing disc anterior compartment, ASP, and myoblasts and activates different sets of genes in each tissue. Some transcriptional targets of Hh signal transduction are common to the disc, ASP, and myoblasts, whereas others are tissue-specific. Signaling in the three tissues is cytoneme-mediated and cytoneme-dependent. We conclude that a single source of Hh in the wing disc regulates cell type-specific responses in three discreet target tissues.SummaryHedgehog produced by the wing imaginal disc signals to wing disc, myoblast and tracheal cells
The combination of mitogenic stimulation and cell cycle arrest induces senescence in equine and human cartilage explants
Authors: Copp Michaela E. , Flanders Margaret C. , Gagliardi Rachel , Gilbertie Jessica M. , Sessions Garrett A. , Chubinskaya Susanna , Loeser Richard F. , Schnabel Lauren V. , Diekman Brian O. 
Published: March 2020

AbstractObjectiveCellular senescence is a phenotypic state characterized by stable cell-cycle arrest, enhanced lysosomal activity, and the secretion of inflammatory molecules and matrix degrading enzymes. Senescence has been implicated in osteoarthritis (OA) pathophysiology; however, the mechanisms that drive senescence induction in cartilage and other joint tissues are unknown. While numerous physiological signals are capable of initiating the senescence phenotype, one emerging theme is that growth-arrested cells convert to senescence in response to sustained mitogenic stimulation. The goal of this study was to develop anin vitroarticular cartilage explant model to investigate the mechanisms of senescence induction.DesignThis study utilized healthy articular cartilage derived from cadaveric equine stifles and human ankles. Explants were irradiated or treated with palbociclib to initiate cell cycle arrest, and mitogenic stimulation was provided by serum-containing medium (horse) and the inclusion of growth factors (human). The primary readout of senescence was a quantitative flow cytometry assay to detect senescence-associated β galactosidase activity (SA-β-gal).ResultsIrradiation of equine explants caused 25.39% of cells to express high levels of SA-β-gal, as compared to 3.82% in control explants (p=0.0031). For human cartilage, explants that received both mitogenic stimulation and cell cycle arrest showed increased rates of senescence induction as compared to baseline control (7.16% vs. 2.34% SA-β-gal high, p=0.0007).ConclusionsTreatment of cartilage explants with mitogenic stimuli in the context of cell-cycle arrest reliably induces high levels of SA-β gal activity, which provides a physiologically relevant model system to investigate the mechanisms of senescence induction.
CROP: A CRISPR/Cas9 guide selection program based on mapping guide variants
Authors: Aprilyanto Victor , Aditama Redi , Tanjung Zulfikar Achmad , Utomo Condro , Liwang Tony 
Published: March 2020

AbstractThe off-target effect, in which DNA cleavage was conducted outside the targeted region, is a major problem which limits the applications of CRISPR/Cas9 genome editing system. CRISPR Off-target Predictor (CROP) is standalone program developed to address this problem by predicting off-target propensity of guide RNAs and thereby allowing the user to select the optimum guides. The approach used by CROP involves generating substitution, deletion and insertion combinations which are then mapped into the reference genome. Based on these mapped variants, scoring and alignment are conducted and then reported as a table comprising the off-target propensity of all guide RNAs from a given gene sequence. The Python script for this program is freely available from:https://github.com/vaprilyanto/crop.
GTP-dependent formation of straight oligomers leads to nucleation of microtubules
Authors: Ayukawa Rie , Iwata Seigo , Imai Hiroshi , Kamimura Shinji , Hayashi Masahito , Ngo Kien Xuan , Minoura Itsushi , Uchimura Seiichi , Makino Tsukasa , Shirouzu Mikako , Shigematsu Hideki , Sekimoto Ken , Gigant Benoît , Muto Etsuko 
Published: March 2020

AbstractMicrotubule (MT) nucleation is essential for cellular activities, but its mechanism is not known because of the difficulty involved in capturing rare stochastic events in the early stage of polymerization. In cells, MTs are nucleated at tubulin concentrations significantly lower than those required for spontaneous nucleation in vitro. The high efficiency of nucleation is due to the synergistic effects of various cellular factors, but the underlying mechanism has not been clarified yet. Here, combining negative stain electron microscopy and kinetic analysis, we demonstrate that the formation of single-stranded straight oligomers with critical size is essential for nucleation in vitro. While the single-stranded oligomers of GTP-tubulin that form prior to MT nucleation show variable curvatures including a few straight oligomers, only curved oligomers are observed among the GDP-bound counterparts. The Y222F mutation in β-tubulin increases the proportion of straight oligomers and drastically accelerates MT nucleation. Our results support a model in which GTP binding causes a small shift in the distribution of oligomer curvature, generating a minor population of straight oligomers compatible with lateral association and further growth to MTs. Our study suggests that cellular factors involved in nucleation promote it via stabilization of straight oligomers.