bluuebunny/crossref_metadata_2025_split huggingface dataset:
Working Memory and Impulsivity and Artificial Neural Networks
Authors: Tiitto Markus Ville , Lodder Robert A. 
Published: October 2020

AbstractAttention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. The treatment of ADHD could potentially be improved with the development of combination therapies targeting multiple systems. Both the number of children diagnosed with ADHD and the use of stimulant medications for its treatment have been rising in recent years, and concern about side-effects and future problems that medication may cause have been increasing. An alternative treatment strategy for ADHD attracting wide interest is the targeting of neuropsychological functioning, such as executive function impairments. Computerized training programs (including video games) have drawn interest as a tool to train improvements in executive function deficits in children with ADHD. Our lab is currently conducting a pilot study to assess the effects of the online game Minecraft as a therapeutic video game (TVG) to train executive function deficits in children with ADHD. The effect of the TVG intervention in combination with stimulants is being investigated to develop a drug-device combination therapy that can address both the dopaminergic dysfunction and executive function deficits present in ADHD. Although the results of this study will be used to guide the clinical development process, additional guidance for the optimization of the executive function training activities will be provided by a computational model of executive functions built with artificial neural networks (ANNs). This model uses ANNs to complete virtual tasks resembling the executive function training activities that the study subjects practice in the Minecraft world, and the schedule of virtual tasks that result in maximum improvements in ANN performance on these tasks will be investigated as a method to inform the selection of training regimens in future clinical studies.
Hidden genetic variation in plasticity provides the potential for rapid adaptation to novel environments
Authors: Walter Greg M. , Clark James , Terranova Delia , Cozzolino Salvatore , Cristaudo Antonia , Hiscock Simon J. , Bridle Jon 
Published: October 2020

AbstractRapid environmental change is forcing populations into novel environments where plasticity will no longer maintain fitness. When populations are exposed to novel environments, evolutionary theory predicts that genetic variation in fitness will increase and should be associated with genetic differences in plasticity. If true, then genetic variation in plasticity can increase adaptive potential in novel environments, and population persistence via rapid adaptation is more likely. To test whether genetic variation in fitness increases in novel environments and is associated with plasticity, we transplanted 8,149 clones of 314 genotypes of a Sicilian daisy (Senecio chrysanthemifolius) within and outside its native range, and quantified genetic variation in fitness, and plasticity in leaf traits and gene expression. Although mean fitness declined by 87% in the novel environment, genetic variance in fitness increased threefold and was correlated with plasticity in leaf traits. High fitness genotypes showed greater plasticity in gene expression, but lower plasticity in most leaf traits. Interestingly, genotypes with greater fitness in the novel environment had the lowest fitness at the native site. These results suggest that standing genetic variation in plasticity could help populations to persist and adapt to novel environments, despite remaining hidden in native environments.
Evidence of shared genetic influences underlying schizophrenia and alcohol use disorder, but not alcohol consumption
Authors: Johnson Emma C. , Kapoor Manav , Hatoum Alexander S. , Zhou Hang , Polimanti Renato , Wendt Frank R. , Walters Raymond K. , Lai Dongbing , Kember Rachel L. , Hartz Sarah , Meyers Jacquelyn L. , Peterson Roseann E. , Ripke Stephan , Bigdeli Tim B. , Fanous Ayman H. , Pato Carlos N. , Pato Michele T. , Goate Alison M. , Kranzler Henry R. , O’Donovan Michael C. , Walters James T.R. , Gelernter Joel , Edenberg Howard J. , Agrawal Arpana 
Published: October 2020

AbstractBackgroundAlcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and recent genome-wide association studies (GWAS) have identified significant genetic correlations between them. In parallel, mounting evidence from GWAS suggests that alcoholconsumptionis only weakly genetically correlated with SCZ, but this has not yet been systematically investigated.MethodsWe used the largest published GWAS for AUD (total cases = 77,822) and SCZ (total cases = 46,827) to systematically identify genetic variants that influence both disorders (in either the same or opposite direction of effect) as well as disorder-specific loci, and contrast our findings with GWAS data for drinks per week (DPW; N = 537,349) as a measure of alcohol consumption.ResultsWe identified 55 independent genome-wide significant SNPs with the same direction of effect on AUD and SCZ, 9 with robust opposite effects, and 99 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001). The genetic correlation between DPW and SCZ (rg= 0.102, SE = 0.022) was significantly lower than that for AUD and SCZ (rg= 0.392, SE = 0.029; p-value of the difference = 9.3e-18), and the genetic covariance between DPW and SCZ was not enriched for any meaningful tissue-specific categories.ConclusionsOur findings provide a detailed view of genetic loci that influence risk of both AUD and SCZ, suggest that biological commonalities underlying genetic variants with an effect on both disorders are manifested in brain tissues, and provide further evidence that SCZ shares meaningful genetic overlap with AUD and not merely alcohol consumption.
Predictive modeling of virus inactivation by UV
Authors: Rockey Nicole C. , Henderson James B. , Chin Kaitlyn , Raskin Lutgarde , Wigginton Krista R. 
Published: October 2020

AbstractDisinfection strategies are commonly applied to inactivate pathogenic viruses in water, food, air, and on surfaces to prevent the spread of infectious diseases. Determining how quickly viruses are inactivated to mitigate health risks is not always feasible due to biosafety restrictions or difficulties with virus culturability. Therefore, methods that would rapidly predict kinetics of virus inactivation by UV254would be valuable, particularly for emerging and difficult-to-culture viruses. We conducted a rapid systematic literature review to collect high-quality inactivation rate constants for a wide range of viruses. Using these data and basic virus information (e.g., genome sequence attributes), we developed and evaluated four different model classes, including linear and non-linear approaches, to find the top performing prediction model. For both the (+) ssRNA and dsDNA virus types, multiple linear regressions were the top performing model classes. In both cases, the cross-validated root mean squared relative prediction errors were similar to those associated with experimental rate constants. We tested the models by predicting and measuring inactivation rate constants for two viruses that were not identified in our systematic review, including a (+) ssRNA mouse coronavirus and a dsDNA marine bacteriophage; the predicted rate constants were within 7% and 71% of the experimental rate constants, respectively. Finally, we applied our models to predict the UV254rate constants of several viruses for which high-quality UV254inactivation data are not available. Our models will be valuable for predicting inactivation kinetics of emerging or difficult-to-culture viruses.
Streptococcus pneumoniae,S. mitis, andS. oralisproduce a phosphatidylglycerol-dependent,ltaS-independent glycerophosphate-linked glycolipid
Authors: Wei Yahan , Joyce Luke R. , Wall Ashley M. , Guan Ziqiang , Palmer Kelli L. 
Published: October 2020

AbstractLipoteichoic acid (LTA) is a cell surface polymer of Gram-positive bacteria. LTA participates in host-microbe interactions including modulation of host immune reactions. It was previously reported that the major human pathogenStreptococcus pneumoniaeand the closely related oral commensalsS. mitisandS. oralisproduce Type IV LTAs. Herein, using liquid chromatography/mass spectrometry (LC/MS)-based lipidomic analysis, we found that in addition to Type IV LTA biosynthetic precursors,S. mitis,S. oralis, andS. pneumoniaealso produce glycerophosphate (Gro-P)-linked dihexosyl-diacylglycerol (DAG), which is a biosynthetic precursor of Type I LTA. Mutants incdsAandpgsAproduce dihexosyl-DAG but lack (Gro-P)-dihexosyl-DAG, indicating that the Gro-P moiety is derived from phosphatidylglycerol (PG), whose biosynthesis requires these genes.S. mitis, but neitherS. pneumoniaenorS. oralis, encodes an ortholog of the PG-dependent Type I LTA synthase,ltaS. By heterologous expression analyses, we confirmed thatS. mitis ltaSconfers poly-(Gro-P) synthesis in bothEscherichia coliandStaphylococcus aureus, and thatS. mitis ltaScan rescue the severe growth defect of aS. aureus ltaSmutant. However, despite these observations, we do not detect a poly-(Gro-P) polymer inS. mitisusing an anti-Type I LTA antibody. Moreover, (Gro-P)-linked dihexosyl-DAG is still synthesized by aS. mitis ltaSmutant, demonstrating thatS. mitisLtaS does not catalyze the transfer of Gro-P from PG to dihexosyl-DAG. Finally, aS. mitis ltaSmutant has increased sensitivity to human serum, demonstrating thatltaSconfers a beneficial but currently undefined function inS. mitis. Overall, our results demonstrate thatS. mitis,S. pneumoniae, andS. oralisproduce a (Gro-P)-linked glycolipid via a PG-dependent,ltaS-independent mechanism.ImportanceLTA is an important cell wall component synthesized by Gram-positive bacteria. Disruption of LTA production can confer severe physiological defects and attenuation of virulence. We report here the detection of a biosynthetic precursor of Type I LTA, in addition to the previously characterized Type IV LTA, in the total lipid extracts ofS. pneumoniae,S. oralis, andS. mitis. Our results indicate that a novel mechanism is responsible for producing the Type I LTA intermediate. Our results are significant because they identify a novel feature ofS. pneumoniae,S. oralis, andS. mitisglycolipid biology.
Inter-species variation in number of bristles on forewings of tiny insects does not impact clap-and-fling aerodynamics
Authors: Kasoju Vishwa T. , Ford Mitchell P. , Ngo Truc T. , Santhanakrishnan Arvind 
Published: October 2020

ABSTRACTFlight-capable miniature insects of body length (BL) < 2 mm typically possess wings with long bristles on the fringes. Though their flight is challenged by needing to overcome significant viscous resistance at chord-based Reynolds number (Rec) on the order of 10, these insects use clap-and-fling mechanism coupled with bristled wings for lift augmentation and drag reduction. However, inter-species variation in the number of bristles (n) and inter-bristle gap (G) to bristle diameter (D) ratio (G/D) and their effects on clap-and-fling aerodynamics remain unknown. Forewing image analyses of 16 species of thrips and 21 species of fairyflies showed thatnand maximum wing span were both positively correlated with BL. We conducted aerodynamic force measurements and flow visualization on simplified physical models of bristled wing pairs that were prescribed to execute clap-and-fling kinematics atRec=10 using a dynamically scaled robotic platform. 23 bristled wing pairs were tested to examine the isolated effects of changing dimensional (G, D, span) and non-dimensional (n, G/D) geometric variables on dimensionless lift and drag. Within biologically observed ranges ofnandG/D, we found that: (a) increasingGprovided more drag reduction than decreasingD; (b) changingnhad minimal impact on lift generation; and (c) varyingG/Dproduced minimal changes in aerodynamic forces. Taken together with the broad variation inn(32-161) across the species considered here, the lack of impact of changingnon lift generation suggests that tiny insects may experience reduced biological pressure to functionally optimizenfor a given wing span.SUMMARY STATEMENTIntegrating morphological analysis of bristled wings seen in miniature insects with physical model experiments, we find that aerodynamic forces are unaffected across the broad biological variation in number of bristles.
Spatio-temporal Memory for Navigation in a Mushroom Body Model
Authors: Zhu Le , Mangan Michael , Webb Barbara 
Published: October 2020

AbstractInsects, despite relatively small brains, can perform complex navigation tasks such as memorising a visual route. The exact format of visual memory encoded by neural systems during route learning and following is still unclear. Here we propose that interconnections between Kenyon cells in the Mushroom Body (MB) could encode spatio-temporal memory of visual motion experienced when moving along a route. In our implementation, visual motion is sensed using an event-based camera mounted on a robot, and learned by a biologically constrained spiking neural network model, based on simplified MB architecture and using modified leaky integrate-and-fire neurons. In contrast to previous image-matching models where all memories are stored in parallel, the continuous visual flow is inherently sequential. Our results show that the model can distinguish learned from unlearned route segments, with some tolerance to internal and external noise, including small displacements. The neural response can also explain observed behaviour taken to support sequential memory in ant experiments. However, obtaining comparable robustness to insect navigation might require the addition of biomimetic pre-processing of the input stream, and determination of the appropriate motor strategy to exploit the memory output.
Lipidomic profiling of clinical prostate cancer reveals targetable alterations in membrane lipid composition
Authors: Butler Lisa M. , Mah Chui Yan , Machiels Jelle , Vincent Andrew D. , Irani Swati , Mutuku Shadrack , Spotbeen Xander , Bagadi Muralidhararao , Waltregny David , Moldovan Max , Dehairs Jonas , Vanderhoydonc Frank , Bloch Katarzyna , Das Rajdeep , Stahl Jurgen , Kench James , Gevaert Thomas , Derua Rita , Waelkens Etienne , Nassar Zeyad D. , Selth Luke A. , Trim Paul J. , Snel Marten F. , Lynn David J. , Tilley Wayne D. , Horvath Lisa G. , Centenera Margaret M. , Swinnen Johannes V. 
Published: October 2020

AbstractDysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Herein, we used quantitative mass spectrometry to define the “lipidome” in prostate tumors with matched benign tissues (n=21), independent tissues (n=47), and primary prostate explants cultured with a clinical AR antagonist, enzalutamide (n=43). Significant differences in lipid composition were detected and spatially visualized in tumors compared to matched benign samples. Notably, tumors featured higher proportions of monounsaturated lipids overall and elongated fatty acid chains in phosphatidylinositol and phosphatidylserine lipids. Significant associations between lipid profile and malignancy were validated in unmatched samples, and PL composition was characteristically altered in patient tissues that responded to AR inhibition. Importantly, targeting of altered tumor-related lipid features, via inhibition of acetyl CoA carboxylase 1, significantly reduced cellular proliferation in tissue explants (n=13). This first characterization of the prostate cancer lipidome in clinical tissues revealed enhanced fatty acid synthesis, elongation and desaturation as tumor-defining features, with potential for therapeutic targeting.
Experimental and mathematical modelling of magnetically labelled mesenchymal stromal cell delivery
Authors: Yeo E.F. , Markides H. , Schade A.T. , Studd A.J. , Oliver J.M. , Waters S.L. , El Haj A.J. 
Published: October 2020

AbstractA key challenge for stem cell therapies is the delivery of therapeutic cells to the repair site. Magnetic targeting has been proposed as a platform for defining clinical sites of delivery more effectively. In this paper we use a combinedin vitroexperimental and mathematical modelling approach to explore the magnetic targeting of mesenchymal stromal cells (MSCs) labelled with magnetic nanoparticles using an external magnet. This study aims to (i) demonstrate the potential of magnetic tagging for MSC delivery, (ii) examine the effect of red blood cells (RBCs) on MSC capture efficacy and (iii) highlight how mathematical models can provide both insight into mechanics of therapy and predictions about cell targetingin vivo.In vitroMSCs are cultured with magnetic nanoparticles and circulated with RBCs over an external magnet. Cell capture efficacy is measured for varying magnetic field strengths and RBC percentages. We use a 2D continuum mathematical model to represent the flow of magnetically tagged MSCs with RBCs. Numerical simulations demonstrate qualitative agreement with experimental results showing better capture with stronger magnetic fields and lower levels of RBCs. We additionally exploit the mathematical model to make hypotheses about the role of extravasation and identify futurein vitroexperiments to quantify this effect.
Abdominal pain assessment in rabbits: using the CANCRS to recognize pain and testing its internal validity over time
Authors: Banchi Penelope , Quaranta Giuseppe , Ricci Alessandro , von Degerfeld Mitzy Mauthe 
Published: October 2020

AbstractA composite scale for pain assessment in rabbits has been previously designed and tested (CANCRS). The present study describes the refinement of the scale and the evaluation of its ability to detect pain variations over time. Furthermore, a comparison between the CANCRS and the Visual Analogue Scale (VAS) has been performed, to underline the differences between an objective (CANCRS) and a subjective (VAS) assessment of abdominal pain. In the first part of the study, 86 rabbits (n=47 heathy patients and n=39 patients with gastrointestinal stasis syndrome) underwent pain assessments with the VAS and the CANCRS. Thirty-two patients with gastrointestinal stasis syndrome participated to the second part of the study. These patients underwent four pain assessments with the CANCRS. The first assessment took place before meloxicam administration and the others after 30, 60 and 90 minutes. The CANCRS showed differences between healthy and diseased rabbits (P= 0.0001), median scores were 5 (IQR 4 - 6) and 9 (IQR 7 - 11) respectively. The VAS showed differences between healthy and diseased rabbits (P= 0.02), the median scores were 4 (IQR 2 - 5.35) and 5.3 (IQR 2.65 - 6.45) respectively. The cut-off scores for the CANCRS and for the VAS for differentiation between healthy and diseased patients were 7 (Sp 89%, Se 79%) and 4.4 (Sp 59%, Se 69%) respectively. Sensitivity and specificity for each parameter of the CANCRS were calculated, in order to obtain weighting factors. Accordingly, the evaluation of respiratory pattern and vocalizations should be excluded from the CANCRS, since their performances in pain evaluation are poor. Internal validity of the CANCRS was tested assessing pain before and after the analgesic treatment and the results showed significancy at each time point. The CANCRS showed better performances than the VAS and its responsiveness to pain variations has been verified.
Assessment of fasting blood glucose, serum electrolyte, albumin, creatinine, urea and lipid profile among hypertensive patients and non-hypertensive participants at wolaita sodo university teaching and referral hospital, SNNPR, Ethiopia
Authors: Haile Berhanu , Wolde Mistire , Gebregziabiher Tatek 
Published: October 2020

AbstractBackgroundHypertension is a silent killer that requires long term management to avoid complications. It is one of major public health problem in developing counties like Ethiopia. Hypertension increases the risk of morbidity and mortality and has negative consequences on the cognitive and physical fitness of productivity in adults.ObjectiveTo assess fasting blood glucose, serum electrolyte, albumin, creatinine, urea, and lipid profile among hypertensive patients and non-hypertensive participants at wolaita sodo teaching and referral hospital.MethodsA comparative cross-sectional study was conducted from December 2019 to February 2020. On the study a total of 156 study participants (78 cases and 78 controls) were involved. Each study participant, after signing informed consent, interviewed about the socio-demographic and anthropometric characteristic features. Then 5ml of the blood sample was collected from each 78 patients with hypertension and each 78 samples from apparently healthy subjects from WSUTRH during the period. Fasting blood glucose, serum electrolyte, albumin, creatinine, urea, and lipid profile level were measured in each group. The Data were analyzed by using Epi data version 3.1 and SPSS version 21.0 software (IBM Corporation, USA) and results were summarized using means and percentages and presented by using figures and tables. P-value < 0.05 was considered to be significant at 95% confidence level. Any abnormal laboratory results of study subjects dispatched and communicated with physicians for better management.ResultsThe mean age of hypertensives and control study groups were 50 ± 10.0 and 51 ±11.3 years respectively. The body mass index of hypertensives and control study groups were 53.4% and 34.2% overweighed respectively. The mean ± SD of fasting blood glucose, total cholesterol, LDL-C, TG, RFT were significantly increases while serum sodium, calcium, albumin, and HDL-Cholesterol significantly decreased in hypertensives when compared with non-hypertensives and serum potassium was no statistical significance among case and control groups.ConclusionIn present study, we observed that the hypertensive group was at risk for developing biochemical alteration in creatinine, urea, fasting blood glucose, lipid profile, electrolytes, and albumin test parameters with an increased period of time.RecommendationRegular measurements of biochemical parameters strongly needed for hypertensive patients.
SVIM-asm: Structural variant detection from haploid and diploid genome assemblies
Authors: Heller David , Vingron Martin 
Published: October 2020

AbstractMotivationWith the availability of new sequencing technologies, the generation of haplotype-resolved genome assemblies up to chromosome scale has become feasible. These assemblies capture the complete genetic information of both parental haplotypes, increase structural variant (SV) calling sensitivity and enable direct genotyping and phasing of SVs. Yet, existing SV callers are designed for haploid genome assemblies only, do not support genotyping or detect only a limited set of SV classes.ResultsWe introduce our method SVIM-asm for the detection and genotyping of six common classes of SVs from haploid and diploid genome assemblies. Compared against the only other existing SV caller for diploid assemblies, DipCall, SVIM-asm detects more SV classes and reached higher F1 scores for the detection of insertions and deletions on two recently published assemblies of the HG002 individual.Availability and ImplementationSVIM-asm has been implemented in Python and can be easily installed via bioconda. Its source code is available at github.com/eldariont/svim-asm.Contactvingron@molgen.mpg.deSupplementary informationSupplementary data are available online.