bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlated flickering of erythrocytes membrane observed with dual time resolved membrane fluctuation spectroscopy under different d-glucose concentrations
Authors: Tapia J. , Vera N. , Aguilar Joao , González M. , Sánchez S. A. , Coelho P. , Saavedra C. , Staforelli J. 
Published: January 2021

AbstractA correlated human red blood cell membrane fluctuation dependent on d-glucose concentration was found with dual time resolved membrane fluctuation spectroscopy (D-TRMFS). This new technique is a modified version of the dual optical tweezers method that has been adapted to measure the mechanical properties of red blood cells (RBCs) at distant membrane points simultaneously, enabling correlation analysis. Mechanical parameters under different d-glucose concentrations were obtained from direct membrane flickering measurements, complemented with membrane fluidity measurements using Laurdan Generalized Polarization (GP) Microscopy. Our results show an increase in the fluctuation amplitude of the lipid bilayer, and a decline in tension value, bending modulus and fluidity as d-glucose concentration increases. Metabolic mechanisms are proposed as explanations for the results.
A translation enhancer element from black beetle virus engages yeast eIF4G1 to drive cap-independent translation initiation
Authors: Trainor Brandon M. , Ghosh Arnab , Pestov Dimitri G. , Hellen Christopher U. T. , Shcherbik Natalia 
Published: January 2021

AbstractCap-independent translation initiation plays crucial roles in fine-tuning gene expression under global translation shutdown conditions. Translation of uncapped or de-capped transcripts can be stimulated by Cap-independent translation enhancer (CITE) elements, but the mechanisms of CITE-mediated translation initiation remain understudied. Here, we characterized a short 5ʹ-UTR RNA sequence from black beetle virus, BBV-seq. Mutational analysis indicates that the entire BBV-seq is required for efficient translation initiation, but this sequence does not operate as an IRES-type module. In yeast cell-free translation extracts, BBV-seq promoted efficient initiation on cap-free mRNA using a scanning mechanism. Moreover, BBV-seq can increase translation efficiency resulting from conventional cap-dependent translation initiation. Using genetic approaches, we found that BBV-seq exploits RNA-binding properties of eIF4G1 to promote initiation. Thus, BBV-seq constitutes a previously uncharacterized short, linear CITE that influences eIF4G1 to initiate 5′ end-dependent, cap-independent translation. These findings bring new insights into CITE-mediated translational control of gene expression.
Influence of levels of automation on the sense of agency during continuous action
Authors: Ueda Sayako , Nakashima Ryoichi , Kumada Takatsune 
Published: January 2021

AbstractRecent advances in automation technology can lead to unsafe situations where operators lose their sense of agency over the automated equipment. On the other hand, increasing evidence has shown that providing operators with opportunities of continuous operation and helping them improve their performance on tasks through automation can boost their sense of agency. However, it is challenging to ensure that the operator maintains a sense of agency when working with a fully automated tool that removes him/her from the control loop. By demonstrating a tracking task in which participants continuously tracked a moving target through a cursor controlled by a joystick under different levels of automation, we illustrate how the participants’ sense of agency and tracking performance were altered in accordance with the level of automation. The results showed that their sense of agency was enhanced by increasing automation but began to decline when the level of automation exceeded 90%. More generally, this suggests that allowing operators a little contribution to control over the continuous operation of an automated tool may be sufficient to maintain their sense of agency while yielding the maximum improvement in performance.
Abundancy of polymorphic CGG repeats in the human genome suggest a broad involvement in neurological disease
Authors: Annear Dale J. , Vandeweyer Geert , Elinck Ellen , Sanchis-Juan Alba , French Courtney E. , Raymond Lucy , Kooy R. Frank 
Published: January 2021

AbstractExpanded CGG-repeats have been linked to neurodevelopmental and neurodegenerative disorders, including the fragile X syndrome and fragile X-associated tremor/ataxia syndrome (FXTAS). We hypothesized that as of yet uncharacterised CGG-repeat expansions within the genome contribute to human disease. To catalogue the CGG-repeats, 544 human whole genomes were analyzed. In total, 6101 unique CGG-repeats were detected of which more than 93% were highly variable in repeat length. Repeats with a median size of 12 repeat units or more were always polymorphic but shorter repeats were often polymorphic, suggesting a potential intergenerational instability of the CGG region even for repeats units with a median length of four or less. 410 of the CGG repeats were associated with known neurodevelopmental disease genes or with strong candidate genes. Based on their frequency and genomic location, CGG repeats may thus be a currently overlooked cause of human disease.
Prevalence and characteristics of cutaneous allodynia in probable migraine
Authors: Han Seung Min , Kim Kyung Min , Cho Soo-Jin , Yang Kwang Ik , Kim Daeyoung , Yun Chang-Ho , Chu Min Kyung 
Published: January 2021

AbstractCutaneous allodynia (CA) is a pain in response to non-nociceptive stimulation and a marker of central sensitisation. Probable migraine (PM) is a migraine subtype that fulfils all but one criterion of migraine. Headache intensity and the disability of individuals with PM are similar or lower than individuals with migraine. This study compared CA prevalence and characteristics of PM and migraine using a nationally representative sample in Korea. The Allodynia Symptom Checklist-12 (ASC-12) was used to assess CA (ASC-12 score ≥ 3). PM and migraine prevalence were 11.6% and 5.0%, respectively. CA prevalence did not significantly differ between PM and migraine (14.5% vs. 16.0%, p = 0.701). Participants with PM with CA reported a higher monthly headache frequency (3.3 ± 4.3 vs. 1.8 ± 3.6, p = 0.044), more severe headache intensity (Visuals Analogue Scale, 6.0 [4.0–7.0] vs. 5.0 [3.0–6.0], p = 0.002), and higher impact of headache (Headache Impact Test-6, 56.3 ± 7.2 vs. 48.3 ± 8.0, p < 0.001) than those without CA. Multiple regression analyses revealed that headache frequency and intensity, anxiety, and depression were significant factors for CA in participants with PM. In conclusion, CA prevalence among participants with PM and migraine were comparable. Anxiety, depression, and headache frequency and intensity were significant factors for CA in participants with PM.
Geometric morphometric investigation of craniofacial morphological change in domesticated silver foxes
Authors: Kistner Timothy M. , Zink Katherine D. , Worthington Steven , Lieberman Daniel E. 
Published: January 2021

AbstractTo test the effects of domestication on craniofacial skeletal morphology, we used three-dimensional geometric morphometrics (GM) along with linear and endocranial measurements to compare selected (domesticated) and unselected foxes from the Russian Farm-Fox Experiment to wild foxes from the progenitor population from which the farmed foxes are derived. Contrary to previous findings, we find that domesticated and unselected foxes show minimal differences in craniofacial shape and size compared to the more substantial differences between the wild foxes and both populations of farmed foxes. GM analyses and linear measurements demonstrate that wild foxes differ from farmed foxes largely in terms of less cranial base flexion, relatively expanded cranial vaults, and increased endocranial volumes. These results challenge the assumption that the unselected population of foxes kept as part of the Russian Farm-Fox experiment are an appropriate proxy for ‘wild’ foxes in terms of craniofacial morphology and highlight the need to include wild populations in further studies of domestication syndrome to disentangle the phenotypic effects of multiple selection pressures. These findings also suggest that marked increases in docility cannot be reliably diagnosed from shape differences in craniofacial skeletal morphology.
Transforming early pharmaceutical assessment of genotoxicity: applying statistical learning to a high throughput, multi end point in vitro micronucleus assay
Authors: Wilson Amy , Grabowski Piotr , Elloway Joanne , Ling Stephanie , Stott Jonathan , Doherty Ann 
Published: January 2021

AbstractTo provide a comprehensive analysis of small molecule genotoxic potential we have developed and validated an automated, high-content, high throughput, image-based in vitro Micronucleus (IVM) assay. This assay simultaneously assesses micronuclei and multiple additional cellular markers associated with genotoxicity. Acoustic dosing (≤ 2 mg) of compound is followed by a 24-h treatment and a 24-h recovery period. Confocal images are captured [Cell Voyager CV7000 (Yokogawa, Japan)] and analysed using Columbus software (PerkinElmer). As standard the assay detects micronuclei (MN), cytotoxicity and cell-cycle profiles from Hoechst phenotypes. Mode of action information is primarily determined by kinetochore labelling in MN (aneugencity) and γH2AX foci analysis (a marker of DNA damage). Applying computational approaches and implementing machine learning models alongside Bayesian classifiers allows the identification of, with 95% accuracy, the aneugenic, clastogenic and negative compounds within the data set (Matthews correlation coefficient: 0.9), reducing analysis time by 80% whilst concurrently minimising human bias. Combining high throughput screening, multiparametric image analysis and machine learning approaches has provided the opportunity to revolutionise early Genetic Toxicology assessment within AstraZeneca. By multiplexing assay endpoints and minimising data generation and analysis time this assay enables complex genotoxicity safety assessments to be made sooner aiding the development of safer drug candidates.
Minor allele of GJA1 gene polymorphism is associated with higher heart rate during atrial fibrillation
Authors: Okamura Sho , Onohara Yuko , Ochi Hidenori , Tokuyama Takehito , Hironobe Naoya , Okubo Yosaku , Ikeuchi Yoshihiro , Miyauchi Shunsuke , Chayama Kazuaki , Kihara Yasuki , Nakano Yukiko 
Published: January 2021

AbstractAtrial fibrillation (AF) tachycardia causes heart failure and requires more attention. The genetic background of individual heart rate (HR) variations during AF are unclear. We hypothesized that HR-associated single nucleotide polymorphisms (SNPs) reported in Genome-Wide Association Studies (GWAS) are also associated with HR during AF. We enrolled patients with persistent AF (311 for screening and 146 for replication) who underwent AF ablation and were genotyped for the 21 h-associated SNPs reported in GWAS. The patients underwent 24-h Holter monitoring before AF ablation and electrophysiological study after AF ablation during sinus rhythm. Only the GJA1 SNP rs1015451 (T>C) was significantly associated with total HR (TT 110,643 ± 17,542 beats/day, TC 116,350 ± 19,060 beats/day, CC 122,163 ± 25,684 beats/day, P = 8.5 × 10−4). We also confirmed this significant association in the replication set. The intra-atrial conduction was faster in AF patients with the GJA1 minor allele than in those without it. Multivariate analysis revealed the presence of a GJA1 SNP rs1015451 additive model, female gender, lower left ventricular ejection fraction, and higher 1:1 atrioventricular nodal conduction were independently associated with higher HR during AF. The GJA1 SNP might be a new genetic marker for AF tachycardia.
Social media reveal ecoregional variation in how weather influences visitor behavior in U.S. National Park Service units
Authors: Wilkins Emily J. , Howe Peter D. , Smith Jordan W. 
Published: January 2021

AbstractDaily weather affects total visitation to parks and protected areas, as well as visitors’ experiences. However, it is unknown if and how visitors change their spatial behavior within a park due to daily weather conditions. We investigated the impact of daily maximum temperature and precipitation on summer visitation patterns within 110 U.S. National Park Service units. We connected 489,061 geotagged Flickr photos to daily weather, as well as visitors’ elevation and distance to amenities (i.e., roads, waterbodies, parking areas, and buildings). We compared visitor behavior on cold, average, and hot days, and on days with precipitation compared to days without precipitation, across fourteen ecoregions within the continental U.S. Our results suggest daily weather impacts where visitors go within parks, and the effect of weather differs substantially by ecoregion. In most ecoregions, visitors stayed closer to infrastructure on rainy days. Temperature also affects visitors’ spatial behavior within parks, but there was not a consistent trend across ecoregions. Importantly, parks in some ecoregions contain more microclimates than others, which may allow visitors to adapt to unfavorable conditions. These findings suggest visitors’ spatial behavior in parks may change in the future due to the increasing frequency of hot summer days.
Lower values of a novel index of Vagal-Neuroimmunomodulation are associated to higher all-cause mortality in two large general population samples with 18 year follow up
Authors: Jarczok Marc N. , Koenig Julian , Thayer Julian F. 
Published: January 2021

AbstractIn recent clinical practice, a biomarker of vagal neuroimmunomodulation (NIM), namely the ratio of vagally-mediated heart rate variability (vmHRV) and CRP, was proposed to index the functionality of the cholinergic anti-inflammatory pathway. This study aims to transfer and extend the previous findings to two general population-based samples to explore the hypothesis that NIM-ratio is associated with all-cause mortality. Two large population studies (MIDUS 2: N = 1255 and Whitehall II wave 5: N = 7870) with complete data from a total of N = 3860 participants (36.1% females; average age = 56.3 years; 11.1% deaths, last exit 18.1 years post inclusion) were available. NIM indices were calculated using the vagally-mediated HRV measure RMSSD divided by measures of CRP (NIMCRP) or IL-6 (NIMIL6). The NIM-ratios were quartiled and entered into age, ethnicity and body mass index adjusted Cox proportional hazards models. For NIMIL6 the lowest quartile was 45% more likely to die during the observed period (max. 18 years follow-up) compared to the highest quartile (HR = 0.55 CI 0.41–0.73; p < .0001). NIMCRP parallel these results. Here we show that an easily computable index of IL-6 inhibition is associated with all-cause mortality in two large general population samples. These results suggest that this index might be useful for risk stratification and warrant further examination.
A nationwide population-based study of incidence and mortality of lung cancer in idiopathic pulmonary fibrosis
Authors: Song Myung Jin , Kim Song Yee , Park Moo Suk , Kang Min Jin , Lee Sang Hoon , Park Seon Cheol 
Published: January 2021

AbstractIdiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer (LC) development; however, there are currently no clinical guidelines for LC surveillance in IPF. This study aimed to investigate the cumulative incidence and survival outcomes of LC in IPF. Using the National Health Insurance Service database, including medical information on people aged ≥ 40 years between 2011 and 2016, we identified IPF patients and confirmed the presence of comorbid LC. Patients diagnosed with IPF in 2011 were washed out, and mortality data were analyzed from 2012 to 2018. A total of 7277 newly diagnosed IPF patients were identified among Korean citizens aged ≥ 40 years (about 50 million people) between 2011 and 2016. Their average age was 71.5 years and 72.8% of them were male. The prevalence of LC in the IPF cases was 6.4%. The cumulative incidence rates of LC in IPF patients who did not have LC at the time of IPF diagnosis were 1.7%, 4.7%, and 7.0%, at 1, 3, and 5 years, respectively. The median time from IPF diagnosis to LC development was 16.3 (Interquartile range, 8.2–28.8) months. The survival rate was significantly lower in the IPF with LC group than the IPF without LC group (P < 0.001). We concluded that IPF increases LC risk, and LC weakens survival outcomes in IPF. Close surveillance for LC development is mandatory for patients with IPF.
Trueness of ten intraoral scanners in determining the positions of simulated implant scan bodies
Authors: Kim Ryan Jin Young , Benic Goran I. , Park Ji-Man 
Published: January 2021

AbstractFew investigations have evaluated the 3-dimensional (3D) accuracy of digital implant scans. The aim of this study was to evaluate the performance of 10 intraoral scanners (IOSs) (CEREC Omnicam, CEREC Primescan, CS 3600, DWIO, i500, iTero Element, PlanScan, Trios 2, Trios 3, and True Definition) in obtaining the accurate positions of 6 cylinders simulating implant scan bodies. Digital scans of each IOS were compared with the reference dataset obtained by means of a coordinate measuring machine. Deviation from the actual positions of the 6 cylinders along the XYZ axes and the overall 3D deviation of the digital scan were calculated. The type of IOSs and position of simulated cylindrical scan bodies affected the magnitude and direction of deviations on trueness. The lowest amount of deviation was found at the cylinder next to the reference origin, while the highest deviation was evident at the contralateral side for all IOSs (p < 0.001). Among the tested IOSs, the CEREC Primescan and Trios 3 had the highest trueness followed by i500, Trios 2, and iTero Element, albeit not statistically significant (p > 0.05), and the DWIO and PlasScan had the lowest trueness in partially edentulous mandible digital implant scans (p < 0.001).
Ultrasound mediated delivery of quantum dots from a proof of concept capsule endoscope to the gastrointestinal wall
Authors: Stewart Fraser , Cummins Gerard , Turcanu Mihnea V. , Cox Benjamin F. , Prescott Alan , Clutton Eddie , Newton Ian P. , Desmulliez Marc P. Y. , Thanou Maya , Mulvana Helen , Cochran Sandy , Näthke Inke 
Published: January 2021

AbstractBiologic drugs, defined as therapeutic agents produced from or containing components of a living organism, are of growing importance to the pharmaceutical industry. Though oral delivery of medicine is convenient, biologics require invasive injections because of their poor bioavailability via oral routes. Delivery of biologics to the small intestine using electronic delivery with devices that are similar to capsule endoscopes is a promising means of overcoming this limitation and does not require reformulation of the therapeutic agent. The efficacy of such capsule devices for drug delivery could be further improved by increasing the permeability of the intestinal tract lining with an integrated ultrasound transducer to increase uptake. This paper describes a novel proof of concept capsule device capable of electronic application of focused ultrasound and delivery of therapeutic agents. Fluorescent markers, which were chosen as a model drug, were used to demonstrate in vivo delivery in the porcine small intestine with this capsule. We show that the fluorescent markers can penetrate the mucus layer of the small intestine at low acoustic powers when combining microbubbles with focused ultrasound during in vivo experiments using porcine models. This study illustrates how such a device could be potentially used for gastrointestinal drug delivery and the challenges to be overcome before focused ultrasound and microbubbles could be used with this device for the oral delivery of biologic therapeutics.
Concentration profiles of ions and particles under hydrodynamic focusing in Y-shaped square microchannel
Authors: Sato Norikazu , Kawashima Daisuke , Takei Masahiro 
Published: January 2021

AbstractThree-dimensional ion and particle concentrations under hydrodynamic focusing in a Y-shaped square microchannel are numerically simulated to clarify the decrease of the ion concentration along the flow direction within the focused particle stream. The simulation model is theoretically governed by the laminar flow and advection–diffusion equations. The governing equations are solved by the finite volume method. The ion and particle concentration distributions at five cross sections after the confluence of the branch channels are analyzed in 30 cases in which the sheath to sample flow rate ratio Qsh/Qsam and the Reynolds number Re are varied as parameters. The results show that the decrease of the cross-sectional average ion concentration along the flow direction within the particle stream $$\overline{c}_{i}$$

c
¯

i

is described by the diffusion length during the residence time with a characteristic velocity scale. In addition, the deformation of the particle stream due to inertial effects is described by a scaled Reynolds number that is a function of the flow rate ratio. The simulated particle stream thicknesses are validated by theory and a simple experiment. This paper reveals the relationship between the ion and particle concentrations and the dimensionless parameters for hydrodynamic focusing in the Y-shaped square microchannel under typical conditions.
Multiplexed CRISPR-Cas9 system in a single adeno-associated virus to simultaneously knock out redundant clock genes
Authors: Kim Boil , Kim Jihoon , Chun Minjeong , Park Inah , Kwak Damhyeon , Choi Mijung , Kim Kyungjin , Choe Han Kyoung 
Published: January 2021

AbstractThe mammalian molecular clock is based on a transcription-translation feedback loop (TTFL) comprising the Period1, 2 (Per1, 2), Cryptochrome1, 2 (Cry1, 2), and Brain and Muscle ARNT-Like 1 (Bmal1) genes. The robustness of the TTFL is attributed to genetic redundancy among some essential clock genes, deterring genetic studies on molecular clocks using genome editing targeting single genes. To manipulate multiple clock genes in a streamlined and efficient manner, we developed a CRISPR-Cas9-based single adeno-associated viral (AAV) system targeting the circadian clock (CSAC) for essential clock genes including Pers, Crys, or Bmal1. First, we tested several single guide RNAs (sgRNAs) targeting individual clock genes in silico and validated their efficiency in Neuro2a cells. To target multiple genes, multiplex sgRNA plasmids were constructed using Golden Gate assembly and packaged into AAVs. CSAC efficiency was evident through protein downregulation in vitro and ablated molecular oscillation ex vivo. We also measured the efficiency of CSAC in vivo by assessing circadian rhythms after injecting CSAC into the suprachiasmatic nuclei of Cas9-expressing knock-in mice. Circadian locomotor activity and body temperature rhythms were severely disrupted in these mice, indicating that our CSAC is a simple yet powerful tool for investigating the molecular clock in vivo.