bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing the results of manual and automated quantitative corneal neuroanalysing modules for beginners
Authors: Wu Po-Ying , Wu Jo-Hsuan , Hsieh Yi-Ting , Chen Lin Chih-Chieh , Cheng Ting , Wu Po-Yi , Hsieh Bing-Jun , Huang Wei-Lun , Huang Sheng-Lung , Chen Wei-Li 
Published: September 2021

AbstractThis study aimed to evaluate the reliability of in vivo confocal microscopic neuroanalysis by beginners using manual and automated modules. Images of sub-basal corneal nerve plexus (SCNP) from 108 images of 18 healthy participants were analyzed by 7 beginner observers using manual (CCMetrics, [CCM]) and automated (ACCMetrics, [ACCM]) module. SCNP parameters analyzed included corneal nerve fiber density (NFD), corneal nerve branch density (NBD), corneal nerve fiber length (NFL), and tortuosity coefficient (TC). The intra-observer repeatability, inter-observer reliability, inter-module agreement, and left–right eye symmetry level of SCNP parameters were examined. All observers showed good intra-observer repeatability using CCM (intraclass correlation coefficient [ICC] > 0.60 for all), except when measuring TC. Two observers demonstrated especially excellent repeatability in analyzing NFD, NBD, and NFL using manual mode, indicating the quality of interpretation may still be observer-dependent. Among all SCNP parameters, NFL had the best inter-observer reliability (Spearman’s rank-sum correlation coefficient [SpCC] and ICC > 0.85 for the 3 original observers) and left–right symmetry level (SpCC and ICC > 0.60). In the additional analysis of inter-observer reliability using results by all 7 observers, only NFL showed good inter-observer reliability (ICC = 0.79). Compared with CCM measurements, values of ACCM measurements were significantly lower, implying a poor inter-module agreement. Our result suggested that performance of quantitative corneal neuroanalysis by beginners maybe acceptable, with NFL being the most reliable parameter, and automated method cannot fully replace manual work.
Factors associating with disability of non-specific low back pain in different subgroups: A hierarchical linear regression analysis
Authors: Miki Takahiro , Higuchi Daisuke , Takebayashi Tsuneo , Samukawa Mina 
Published: September 2021

AbstractThis study aimed to explore factors associating with disability, which means physical impairment affecting a person’s mobility, capacity, stamina, or agility, of non-specific low back pain (NSLBP) of the acute and non-acute groups. Two hundred thirty-five patients with NSLBP of less than 8 weeks’ duration as acute groups (n = 124) and more than 8 weeks’ duration as non-acute group (n = 111) were recruited. It was collected data on pain intensity, disability and psychosocial factors, including pain catastrophising, fear of movement and pain self-efficacy. Disability was measured Roland Morris Disability Questionnaire. A hierarchical multiple regression analysis was performed to analyse factors associating with disability of the acute and non-acute groups. The Result was that explanatory power increased with each additional variable of the order of demographic characteristics, pain intensity and psychosocial factors for both groups. Pain intensity, pain catastrophising and pain self-efficacy had significant explanatory power, with pain self-efficacy having the most significant association on the acute group. Only pain self-efficacy having the most significant association on disability of the non-acute group. In conclusion, the factors associating with disability differed depending on the duration of the disease, and pain self-efficacy might be one of the factors associating with disability of patients with NSLBP.
Verification and dissection of one quantitative trait locus for grain size and weight on chromosome 1 in rice
Authors: Cheng Yi-chen , Li Guan , Yin Man , Adegoke Tosin Victor , Wang Yi-feng , Tong Xiao-hong , Zhang Jian , Ying Jie-zheng 
Published: September 2021

AbstractGrain size and weight are the key traits determining rice quality and yield and are mainly controlled by quantitative trait loci (QTL). In this study, one minor QTL that was previously mapped in the marker interval of JD1009-JD1019 using the Huanghuazhan/Jizi1560 (HHZ/JZ1560) recombinant inbred line (RIL) population, qTGW1-2, was validated to regulate grain size and weight across four rice-growing seasons using twenty-one near isogenic line (NIL)-F2 populations. The twenty-one populations were in two types of genetic background that were derived from the same parents HHZ and JZ1560. Twelve F9, F10 or F11 NIL-F2 populations with the sequential residual heterozygous regions covering JD1009-RM6840 were developed from one residual heterozygote (RH) in the HHZ/JZ1560 RIL population, and the remaining nine BC3F3, BC3F4 or BC3F5 NIL-F2 populations with the sequential residual heterozygous regions covering JD1009-RM6840 were constructed through consecutive backcrosses to the recurrent parent HHZ followed with marker assistant selection in each generation. Based on the QTL analysis of these genetic populations, qTGW1-2 was successfully confirmed to control grain length, width and weight and further dissected into two QTLs, qTGW1-2a and qTGW1-2b, which were respectively narrowed down to the marker intervals of JD1139-JD1127 (~ 978.2-kb) and JD1121-JD1102 (~ 54.8-kb). Furthermore, the two types of NIL-F2 populations were proved to be able to decrease the genetic background noise and increase the detection power of minor QTL. These results provided an important basis for further map-based cloning and molecular design breeding with the two QTLs in rice.
Terrestrial mesopredators did not increase after top-predator removal in a large-scale experimental test of mesopredator release theory
Authors: Castle Geoff , Smith Deane , Allen Lee R. , Allen Benjamin L. 
Published: September 2021

AbstractRemoval or loss of top-predators has been predicted to cause cascading negative effects for ecosystems, including mesopredator release. However, reliable evidence for these processes in terrestrial systems has been mixed and equivocal due, in large part, to the systemic and continued use of low-inference study designs to investigate this issue. Even previous large-scale manipulative experiments of strong inferential value have been limited by experimental design features (i.e. failure to prevent migration between treatments) that constrain possible inferences about the presence or absence of mesopredator release effects. Here, we build on these previous strong-inference experiments and report the outcomes of additional large-scale manipulative experiments to eradicate Australian dingoes from two fenced areas where dingo migration was restricted and where theory would predict an increase in extant European red foxes, feral cats and goannas. We demonstrate the removal and suppression of dingoes to undetectable levels over 4–5 years with no corresponding increases in mesopredator relative abundances, which remained low and stable throughout the experiment at both sites. We further demonstrate widespread absence of negative relationships between predators, indicating that the mechanism underpinning predicted mesopredator releases was not present. Our results are consistent with all previous large-scale manipulative experiments and long-term mensurative studies which collectively demonstrate that (1) dingoes do not suppress red foxes, feral cats or goannas at the population level, (2) repeated, temporary suppression of dingoes in open systems does not create mesopredator release effects, and (3) removal and sustained suppression of dingoes to undetectable levels in closed systems does not create mesopredator release effects either. Our experiments add to similar reports from North America, Asia, Europe and southern Africa which indicate that not only is there a widespread absence of reliable evidence for these processes, but there is also a large and continually growing body of experimental evidence of absence for these processes in many terrestrial systems. We conclude that although sympatric predators may interact negatively with each other on smaller spatiotemporal scales, that these negative interactions do not always scale-up to the population level, nor are they always strong enough to create mesopredator suppression or release effects.
Embryotoxic activity of 3C protease of human hepatitis A virus in developing Danio rerio embryos
Authors: Selina Polina I. , Karaseva Maria A. , Komissarov Alexey A. , Safina Dina R. , Lunina Nataliya A. , Roschina Marina P. , Sverdlov Eugene D. , Demidyuk Ilya V. , Kostrov Sergey V. 
Published: September 2021

AbstractThe 3C protease is a key factor in picornavirus-induced pathologies with a comprehensive action on cell targets. However, the effects induced by the enzyme have not been described at the organismic level. Here, the model of developing Danio rerio embryos was used to analyze possible toxic effects of the 3C protease of human hepatitis A virus (3Cpro) at the whole-body level. The transient 3Cpro expression had a notable lethal effect and induced a number of specific abnormalities in Danio rerio embryos within 24 h. These effects are due to the proteolytic activity of the enzyme. At the same time, the 3Cpro variant with reduced catalytic activity (3Cmut) increased the incidence of embryonic abnormalities; however, this effect was smaller compared to the native enzyme form. While the expression of 3Cmut increased the overall rate of abnormalities, no predominance of specific ones was observed. The data obtained point to a presence significant impact of picornavirus 3Cprotease at the whole-organism level and make contribution to the study of the infectious process caused by human hepatitis A virus.
Risk assessment of thromboembolic events in hospitalized cancer patients
Authors: Nichetti Federico , Ligorio Francesca , Montelatici Giulia , Porcu Luca , Zattarin Emma , Provenzano Leonardo , Franza Andrea , Lalli Luca , de Braud Filippo , Platania Marco 
Published: September 2021

AbstractHospitalized cancer patients are at increased risk for Thromboembolic Events (TEs). As untailored thromboprophylaxis is associated with hemorrhagic complications, the definition of a risk-assessment model (RAM) in this population is needed. INDICATE was a prospective observational study enrolling hospitalized cancer patients, with the primary objective of assessing the Negative Predictive Value (NPV) for TEs during hospitalization and within 45 days from discharge of low-grade Khorana Score (KS = 0). Secondary objectives were to assess KS Positive Predictive Value (PPV), the impact of TEs on survival and the development of a new RAM. Assuming 7% of TEs in KS = 0 patients as unsatisfactory percentage and 3% of as satisfactory, 149 patients were needed to detect the favorable NPV with one-sided α = 0.10 and power = 0.80. Stepwise logistic regression was adopted to identify variables included in a new RAM. Among 535 enrolled patients, 153 (28.6%) had a KS = 0. The primary study objective was met: 29 (5.4%) TEs were diagnosed, with 7 (4.6%) cases in the KS = 0 group (NPV = 95.4%, 95% CI 90.8–98.1%; one-sided p = 0.084). However, the PPV was low (5.7%, 95% CI 1.9–12.8%); a new RAM based on albumin (OR 0.34, p = 0.003), log(LDH) (OR 1.89, p = 0.023) and presence of vascular compression (OR 5.32, p < 0.001) was developed and internally validated. Also, TEs were associated with poorer OS (median, 5.7 vs 24.8 months, p < 0.001). INDICATE showed that the KS has a good NPV but poor PPV for TEs in hospitalized cancer patients. A new RAM was developed, and deserves further assessment in external cohorts.
Uncertainty-induced instantaneous speed and acceleration of a levitated particle
Authors: Ornigotti Luca , Filip Radim 
Published: September 2021

AbstractLevitating nanoparticles trapped in optical potentials at low pressure open the experimental investigation of nonlinear ballistic phenomena. With engineered non-linear potentials and fast optical detection, the observation of autonomous transient mechanical effects, such as instantaneous speed and acceleration stimulated purely by initial position uncertainty, are now achievable. By using parameters of current low pressure experiments, we simulate and analyse such uncertainty-induced particle ballistics in a cubic optical potential demonstrating their evolution, faster than their standard deviations, justifying the feasibility of the experimental verification. We predict, the maxima of instantaneous speed and acceleration distributions shift alongside the potential force, while the maximum of position distribution moves opposite to it. We report that cryogenic cooling is not necessary in order to observe the transient effects, while a low uncertainty in initial particle speed is required, via cooling or post-selection, to not mask the effects. These results stimulate the discussion for both attractive stochastic thermodynamics, and extension of recently explored quantum regime.
Deep neural network for detecting arbitrary precision peptide features through attention based segmentation
Authors: Zohora Fatema Tuz , Rahman M. Ziaur , Tran Ngoc Hieu , Xin Lei , Shan Baozhen , Li Ming 
Published: September 2021

AbstractA promising technique of discovering disease biomarkers is to measure the relative protein abundance in multiple biofluid samples through liquid chromatography with tandem mass spectrometry (LC-MS/MS) based quantitative proteomics. The key step involves peptide feature detection in the LC-MS map, along with its charge and intensity. Existing heuristic algorithms suffer from inaccurate parameters and human errors. As a solution, we propose PointIso, the first point cloud based arbitrary-precision deep learning network to address this problem. It consists of attention based scanning step for segmenting the multi-isotopic pattern of 3D peptide features along with the charge, and a sequence classification step for grouping those isotopes into potential peptide features. PointIso achieves 98% detection of high-quality MS/MS identified peptide features in a benchmark dataset. Next, the model is adapted for handling the additional ‘ion mobility’ dimension and achieves 4% higher detection than existing algorithms on the human proteome dataset. Besides contributing to the proteomics study, our novel segmentation technique should serve the general object detection domain as well.
An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank
Authors: Li Xue , van Geffen Jos , van Weele Michiel , Zhang Xiaomeng , He Yazhou , Meng Xiangrui , Timofeeva Maria , Campbell Harry , Dunlop Malcolm , Zgaga Lina , Theodoratou Evropi 
Published: September 2021

AbstractA growing body of evidence suggests that vitamin D deficiency has been associated with an increased susceptibility to viral and bacterial respiratory infections. In this study, we aimed to examine the association between vitamin D and COVID-19 risk and outcomes. We used logistic regression to identify associations between vitamin D variables and COVID-19 (risk of infection, hospitalisation and death) in 417,342 participants from UK Biobank. We subsequently performed a Mendelian Randomisation (MR) study to look for evidence of a causal effect. In total, 1746 COVID-19 cases (399 deaths) were registered between March and June 2020. We found no significant associations between COVID-19 infection risk and measured 25-OHD levels after adjusted for covariates, but this finding is limited by the fact that the vitamin D levels were measured on average 11 years before the pandemic. Ambient UVB was strongly and inversely associated with COVID-19 hospitalization and death overall and consistently after stratification by BMI and ethnicity. We also observed an interaction that suggested greater protective effect of genetically-predicted vitamin D levels when ambient UVB radiation is stronger. The main MR analysis did not show that genetically-predicted vitamin D levels are causally associated with COVID-19 risk (OR = 0.77, 95% CI 0.55–1.11, P = 0.160), but MR sensitivity analyses indicated a potential causal effect (weighted mode MR: OR = 0.72, 95% CI 0.55–0.95, P = 0.021; weighted median MR: OR = 0.61, 95% CI 0.42–0.92, P = 0.016). Analysis of MR-PRESSO did not find outliers for any instrumental variables and suggested a potential causal effect (OR = 0.80, 95% CI 0.66–0.98, p-val = 0.030). In conclusion, the effect of vitamin D levels on the risk or severity of COVID-19 remains controversial, further studies are needed to validate vitamin D supplementation as a means of protecting against worsened COVID-19.
Discovering and comparing types of general practitioner practices using geolocational features and prescribing behaviours by means of K-means clustering
Authors: Booth Frederick G. , R Bond Raymond , D Mulvenna Maurice , Cleland Brian , McGlade Kieran , Rankin Debbie , Wallace Jonathan , Black Michaela 
Published: September 2021

AbstractTraditionally General Practitioner (GP) practices have been labelled as being in Rural, Urban or Semi-Rural areas with no statistical method of identifying which practices fall into each category. The main aim of this study is to investigate whether location and other characteristics can provide a tautology to identify different types of GP practice and compare the prescribing behaviours associated with the different practice types. To achieve this monthly open source prescription data were analysed by practice considering location, practice size, population density and deprivation rankings. One year’s data was subjected to k-means clustering with the results showing that only two different types of GP practice can be classified that are dependent on location characteristics in Northern Ireland. Traditional labels did not describe the two classifications fully and new classifications of Metropolitan and Non-Metropolitan were used. Whilst prescribing patterns were generally similar, it was found that Metropolitan practices generally had higher prescribing rates than Non-Metropolitan practices. Examining prescribing behaviours in accordance with British National Formulary (BNF) categories (known as chapters) showed that Chapter 4 (Central Nervous System) was responsible for most of the difference in prescribing levels. Within Chapter 4 higher prescribing levels were attributable to Analgesic and Antidepressant prescribing. The clusters were finally examined regarding the level of deprivation experienced in the area in which the practice was located. This showed that the Metropolitan cluster, having higher prescription rates, also had a higher proportion of practices located in highly deprived areas making deprivation a contributing factor.
Duchenne muscular dystrophy cell culture models created by CRISPR/Cas9 gene editing and their application in drug screening
Authors: Soblechero-Martín Patricia , Albiasu-Arteta Edurne , Anton-Martinez Aina , de la Puente-Ovejero Laura , Garcia-Jimenez Iker , González-Iglesias Gabriela , Larrañaga-Aiestaran Irene , López-Martínez Andrea , Poyatos-García Javier , Ruiz-Del-Yerro Estíbaliz , Gonzalez Federico , Arechavala-Gomeza Virginia 
Published: September 2021

AbstractGene editing methods are an attractive therapeutic option for Duchenne muscular dystrophy, and they have an immediate application in the generation of research models. To generate myoblast cultures that could be useful in in vitro drug screening, we have optimised a CRISPR/Cas9 gene edition protocol. We have successfully used it in wild type immortalised myoblasts to delete exon 52 of the dystrophin gene, modelling a common Duchenne muscular dystrophy mutation; and in patient’s immortalised cultures we have deleted an inhibitory microRNA target region of the utrophin UTR, leading to utrophin upregulation. We have characterised these cultures by demonstrating, respectively, inhibition of dystrophin expression and overexpression of utrophin, and evaluating the expression of myogenic factors (Myf5 and MyH3) and components of the dystrophin associated glycoprotein complex (α-sarcoglycan and β-dystroglycan). To demonstrate their use in the assessment of DMD treatments, we have performed exon skipping on the DMDΔ52-Model and have used the unedited DMD cultures/ DMD-UTRN-Model combo to assess utrophin overexpression after drug treatment. While the practical use of DMDΔ52-Model is limited to the validation to our gene editing protocol, DMD-UTRN-Model presents a possible therapeutic gene edition target as well as a useful positive control in the screening of utrophin overexpression drugs.
Deciphering complex genome rearrangements in C. elegans using short-read whole genome sequencing
Authors: Maroilley Tatiana , Li Xiao , Oldach Matthew , Jean Francesca , Stasiuk Susan J. , Tarailo-Graovac Maja 
Published: September 2021

AbstractGenomic rearrangements cause congenital disorders, cancer, and complex diseases in human. Yet, they are still understudied in rare diseases because their detection is challenging, despite the advent of whole genome sequencing (WGS) technologies. Short-read (srWGS) and long-read WGS approaches are regularly compared, and the latter is commonly recommended in studies focusing on genomic rearrangements. However, srWGS is currently the most economical, accurate, and widely supported technology. In Caenorhabditis elegans (C. elegans), such variants, induced by various mutagenesis processes, have been used for decades to balance large genomic regions by preventing chromosomal crossover events and allowing the maintenance of lethal mutations. Interestingly, those chromosomal rearrangements have rarely been characterized on a molecular level. To evaluate the ability of srWGS to detect various types of complex genomic rearrangements, we sequenced three balancer strains using short-read Illumina technology. As we experimentally validated the breakpoints uncovered by srWGS, we showed that, by combining several types of analyses, srWGS enables the detection of a reciprocal translocation (eT1), a free duplication (sDp3), a large deletion (sC4), and chromoanagenesis events. Thus, applying srWGS to decipher real complex genomic rearrangements in model organisms may help designing efficient bioinformatics pipelines with systematic detection of complex rearrangements in human genomes.
KCTD15 deregulation is associated with alterations of the NF-κB signaling in both pathological and physiological model systems
Authors: Smaldone Giovanni , Coppola Luigi , Pane Katia , Franzese Monica , Beneduce Giuliana , Parasole Rosanna , Menna Giuseppe , Vitagliano Luigi , Salvatore Marco , Mirabelli Peppino 
Published: September 2021

AbstractLike other KCTD proteins, KCTD15 is involved in important albeit distinct biological processes as cancer, neural crest formation, and obesity. Here, we characterized the role of KCTD15 in different physiological/pathological states to gain insights into its diversified function(s). The silencing of KCTD15 in MLL-rearranged leukemia models induced attenuation of the NF-κB pathway associated with a downregulation of pIKK-β and pIKB-α. Conversely, the activation of peripheral blood T cells upon PMA/ionomycin stimulation remarkably upregulated KCTD15 and, simultaneously, pIKK-β and pIKB-α. Moreover, a significant upregulation of KCTD15 was also observed in CD34 hematopoietic stem/progenitor cells where the NF-κB pathway is physiologically activated. The association between KCTD15 upregulation and increased NF-κB signaling was confirmed by luciferase assay as well as KCTD15 and IKK-β proximity ligation and immunoprecipitation experiments. The observed upregulation of IKK-β by KCTD15 provides a novel and intriguing interpretative key for understanding the protein function in a wide class of physiological/pathological conditions ranging from neuronal development to cancer and obesity/diabetes.