bluuebunny/crossref_metadata_2025_split huggingface dataset:
An extreme-phenotype genome‐wide association study identifies candidate cannabinoid pathway genes in Cannabis
Authors: Welling Matthew T. , Liu Lei , Kretzschmar Tobias , Mauleon Ramil , Ansari Omid , King Graham J. 
Published: October 2020

AbstractCannabis produces a class of isoprenylated resorcinyl polyketides known as cannabinoids, a subset of which are medically important and exclusive to this plant. The cannabinoid alkyl group is a critical structural feature that governs therapeutic activity. Genetic enhancement of the alkyl side-chain could lead to the development of novel chemical phenotypes (chemotypes) for pharmaceutical end-use. However, the genetic determinants underlying in planta variation of cannabinoid alkyl side-chain length remain uncharacterised. Using a diversity panel derived from the Ecofibre Cannabis germplasm collection, an extreme-phenotype genome-wide association study (XP-GWAS) was used to enrich for alkyl cannabinoid polymorphic regions. Resequencing of chemotypically extreme pools revealed a known cannabinoid synthesis pathway locus as well as a series of chemotype-associated genomic regions. One of these regions contained a candidate gene encoding a β-keto acyl carrier protein (ACP) reductase (BKR) putatively associated with polyketide fatty acid starter unit synthesis and alkyl side-chain length. Association analysis revealed twenty-two polymorphic variants spanning the length of this gene, including two nonsynonymous substitutions. The success of this first reported application of XP-GWAS for an obligate outcrossing and highly heterozygote plant genus suggests that this approach may have generic application for other plant species.
Decompressive craniectomy of post-traumatic brain injury: an in silico modelling approach for intracranial hypertension management
Authors: Lambride Chryso , Christodoulou Nicolas , Michail Anna , Vavourakis Vasileios , Stylianopoulos Triantafyllos 
Published: October 2020

AbstractTraumatic brain injury (TBI) causes brain edema that induces increased intracranial pressure and decreased cerebral perfusion. Decompressive craniectomy has been recommended as a surgical procedure for the management of swollen brain and intracranial hypertension. Proper location and size of a decompressive craniectomy, however, remain controversial and no clinical guidelines are available. Mathematical and computational (in silico) models can predict the optimum geometric conditions and provide insights for the brain mechanical response following a decompressive craniectomy. In this work, we present a finite element model of post-traumatic brain injury and decompressive craniectomy that incorporates a biphasic, nonlinear biomechanical model of the brain. A homogenous pressure is applied in the brain to represent the intracranial pressure loading caused by the tissue swelling and the models calculate the deformations and stresses in the brain as well as the herniated volume of the brain tissue that exits the skull following craniectomy. Simulations for different craniectomy geometries (unilateral, bifrontal and bifrontal with midline bar) and sizes are employed to identify optimal clinical conditions of decompressive craniectomy. The reported results for the herniated volume of the brain tissue as a function of the intracranial pressure loading under a specific geometry and size of craniectomy are exceptionally relevant for decompressive craniectomy planning.
A rigorous assessment and comparison of enumeration methods for environmental viruses
Authors: Kaletta Judith , Pickl Carolin , Griebler Christian , Klingl Andreas , Kurmayer Rainer , Deng Li 
Published: October 2020

AbstractDetermining exact viral titers in a given sample is essential for many environmental and clinical applications, e.g., for studying viral ecology or application of bacteriophages for food safety. However, virus quantification is not a simple task, especially for complex environmental samples. While clonal viral isolates can be quantified with relative high accuracy using virus-specific methods, i.e., plaque assay or quantitative real-time PCR, these methods are not valid for complex and diverse environmental samples. Moreover, it is not yet known how precisely laser-based methods, i.e., epifluorescence microscopy, flow cytometry, and nanoparticle tracking analysis, quantify environmental viruses. In the present study, we compared five state-of-the-art viral quantification methods by enumerating four model viral isolates of different genome and size characteristics as well as four different environmental water samples. Although Nanoparticle tracking analysis combined with gentle staining at 30 °C could be confirmed by this study to be a reliable quantification technique for tested environmental samples, environmental samples still lack an universally applicable and accurate quantification method. Special attention has to be put on optimal sample concentrations as well as optimized sample preparations, which are specific for each method. As our results show the inefficiency when enumerating small, or single-stranded DNA or RNA viruses, the global population of viruses is presumably higher than expected.
Microglial response to experimental periodontitis in a murine model of Alzheimer’s disease
Authors: Kantarci Alpdogan , Tognoni Christina M. , Yaghmoor Wael , Marghalani Amin , Stephens Danielle , Ahn Jae-Yong , Carreras Isabel , Dedeoglu Alpaslan 
Published: October 2020

AbstractPeriodontal disease (PD) has been suggested to be a risk factor for Alzheimer’s disease (AD). We tested the impact of ligature-induced PD on 5xFAD mice and WT littermates. At baseline, 5xFAD mice presented significant alveolar bone loss compared to WT mice. After the induction of PD, both WT and 5xFAD mice experienced alveolar bone loss. PD increased the level of Iba1-immunostained microglia in WT mice. In 5xFAD mice, PD increased the level of insoluble Aβ42. The increased level in Iba1 immunostaining that parallels the accumulation of Aβ in 5xFAD mice was not affected by PD except for a decrease in the dentate gyrus. Analysis of double-label fluorescent images showed a decline in Iba1 in the proximity of Aβ plaques in 5xFAD mice with PD compared to those without PD suggesting a PD-induced decrease in plaque-associated microglia (PAM). PD reduced IL-6, MCP-1, GM-CSF, and IFN-γ in brains of WT mice and reduced IL-10 in 5xFAD mice. The data demonstrated that PD increases neuroinflammation in WT mice and disrupts the neuroinflammatory response in 5xFAD mice and suggest that microglia is central to the association between PD and AD.
Optimal treatment strategy of fremanezumab in migraine prevention: a systematic review with network meta-analysis of randomized clinical trials
Authors: Huang I-Hsin , Wu Po-Chien , Lee Ya-Han , Kang Yi-No 
Published: October 2020

AbstractIdentifying the optimal fremanezumab treatment strategy is crucial in treating patients with migraines. The optimal strategy was investigated by assessing the cumulative 50% reduction rate (50%CRR), cumulative 75% reduction rate (75%CRR), reduction in the number of migraine days, treatment-related adverse events, and serious adverse events in patients treated with fremanezumab 225 mg monthly (225 mg), 675 mg monthly (675 mg), 900 mg monthly (900 mg), a single high dose of 675 mg (S675mg), 675 mg at baseline with 225 mg monthly (675/225 mg), and placebo. Biomedical databases were searched for randomized controlled trials on this topic, and data were individually extracted. Risk ratios and mean differences were used to present the pooled results. The surface under the cumulative ranking curve (SUCRA) was used to determine the effects of the medication strategies of fremanezumab. Five trials (n = 3404) were used to form a six-node network meta-analysis. All fremanezumab medication strategies displayed significantly higher cumulative 50% reduction rates than the placebo. The SUCRA revealed that treatment with 675 mg yielded the highest 50%CRR value (mean rank = 2.5). S675 mg was the only treatment with significantly higher 75%CRR reduction rate than placebo, whereas the SUCRA for 225 mg displayed the highest mean rank (2.2). Moreover, 225 mg (mean rank = 2.2) and S675 mg (mean rank = 2.2) presented lower probabilities of serious adverse events. Collectively, S675mg and 225 mg exhibited the optimal balance between efficacy and safety within three months. Long-term efficacy and safety remain unclear, and future studies should further evaluate the long-term outcomes.
The influence of afferent input on somatosensory suppression during grasping
Authors: Broda Maximilian Davide , Fiehler Katja , Voudouris Dimitris 
Published: October 2020

AbstractThe processing of somatosensory information is hampered on a moving limb. This suppression has been widely attributed to sensorimotor predictions that suppress the associated feedback, though postdictive mechanisms are also involved. Here, we investigated the extent to which suppression on a limb is influenced by backward somatosensory signals, such as afferents associated with forces that this limb applies. Participants grasped and lifted objects of symmetric and asymmetric mass distributions using a precision grip. We probed somatosensory processing at the moment of the grasp by presenting a vibrotactile stimulus either on the thumb or index finger and asked participants to report if they felt this stimulus. Participants applied greater forces with the thumb and index finger for objects loaded to the thumb’s or index finger’s endpoint, respectively. However, suppression was not influenced by the different applied forces. Suppression on the digits remained constant both when grasping heavier objects, and thus applying even greater forces, and when probing suppression on the skin over the muscle that controlled force application. These results support the idea that somatosensory suppression is predictive in nature while backward masking may only play a minor role in somatosensory processing on the moving hand, at least in this context.
The incidence and clinical features of PEGylated filgrastim-induced acute aortitis in patients with breast cancer
Authors: Lee Sang Yoon , Kim Eun Kyoung , Kim Ji-Yeon , Park Taek-kyu , Choi Seung-Hyuk , Im Young-Hyuck , Kim Min Yeong , Park Yeon Hee , Kim Duk-Kyung 
Published: October 2020

AbstractAlthough PEGylated filgrastim-induced aortitis is very rare and unknown clinically, some cases were reported and increasing, especially in breast cancer patients. The present study investigated the prevalence, clinical features and treatment of aortitis induced by PEGylated filgrastim in patients with breast cancer. A total of 2068 consecutive patients who underwent neoadjuvant/adjuvant chemotherapy with PEGylated filgrastim for breast cancer were enrolled. From the medical record, clinical, laboratory, medication, and imaging evaluation findings were collected. PEGylated filgrastim-induced aortitis was established in 0.3% of the study population. Common clinical presentations included extremely high fever and chest/back pain with high levels of inflammatory markers without any signs of infection. Contrast-enhanced computed tomography scans revealed typical enhancing wall thickening and periaortic soft tissue infiltration at various levels of aorta. All patients improved rapidly after treatment with modest doses of prednisolone (0.5 mg/kg/day) without any complications. Clinicians should be aware of aortitis as a possible complication of granulocyte-colony stimulating factor therapy, especially PEGylated filgrastim, given the frequent misdiagnoses in neutropenic patients undergoing chemotherapy.
The effects of background music on neural responses during reading comprehension
Authors: Du Meng , Jiang Jun , Li Zhemin , Man Dongrui , Jiang Cunmei 
Published: October 2020

AbstractThe effects of background speech or noise on visually based cognitive tasks has been widely investigated; however, little is known about how the brain works during such cognitive tasks when music, having a powerful function of evoking emotions, is used as the background sound. The present study used event-related potentials to examine the effects of background music on neural responses during reading comprehension and their modulation by musical arousal. Thirty-nine postgraduates judged the correctness of sentences about world knowledge without or with background music (high-arousal music and low-arousal music). The participants’ arousal levels were reported during the experiment. The results showed that the N400 effect, elicited by world knowledge violations versus correct controls, was significantly smaller for silence than those for high- and low-arousal music backgrounds, with no significant difference between the two musical backgrounds. This outcome might have occurred because the arousal levels of the participants were not affected by the high- and low-arousal music throughout the experiment. These findings suggest that background music affects neural responses during reading comprehension by increasing the difficulty of semantic integration, and thus extend the irrelevant sound effect to suggest that the neural processing of visually based cognitive tasks can also be affected by music.
Bidirectional rotation control of a carbon fiber in nematic liquid crystal using AC electric field
Authors: Lee Jun-Yong , Yu Jeong-Seon , Kim Jong-Hyun 
Published: October 2020

AbstractColloidal particles dispersed in nematic liquid crystals are aligned along the orientation that minimizes the elastic free energy. Through applying an electric field to a nematic colloidal system, the orientation of the director can change. Consequently, colloidal particles realign to minimize the total free energy, which is the sum of the elastic and electric free energies. Herein, we demonstrate that if the preferred rotation directions given by the electric and elastic free energies are different during realignment, the rotation direction of the particle can be controlled by how we apply the electric field. When the strength of the electric field gradually increases, the particles rotate in the same direction as the rotation of the director. However, when a sufficiently high electric field is suddenly applied, the particles rotate in the opposite direction. In this study, we analyzed the effect of free energy on the bidirectional rotation behavior of the particles using a theoretical model. This study provides an effective approach to control the rotational behavior of colloidal particles over a wide-angle range between two orientational local minima.
The pathogenic S688Y mutation in the ligand-binding domain of the GluN1 subunit regulates the properties of NMDA receptors
Authors: Skrenkova Kristyna , Song Jae-man , Kortus Stepan , Kolcheva Marharyta , Netolicky Jakub , Hemelikova Katarina , Kaniakova Martina , Krausova Barbora Hrcka , Kucera Tomas , Korabecny Jan , Suh Young Ho , Horak Martin 
Published: October 2020

AbstractAlthough numerous pathogenic mutations have been identified in various subunits of N-methyl-D-aspartate receptors (NMDARs), ionotropic glutamate receptors that are central to glutamatergic neurotransmission, the functional effects of these mutations are often unknown. Here, we combined in silico modelling with microscopy, biochemistry, and electrophysiology in cultured HEK293 cells and hippocampal neurons to examine how the pathogenic missense mutation S688Y in the GluN1 NMDAR subunit affects receptor function and trafficking. We found that the S688Y mutation significantly increases the EC50 of both glycine and d-serine in GluN1/GluN2A and GluN1/GluN2B receptors, and significantly slows desensitisation of GluN1/GluN3A receptors. Moreover, the S688Y mutation reduces the surface expression of GluN3A-containing NMDARs in cultured hippocampal neurons, but does not affect the trafficking of GluN2-containing receptors. Finally, we found that the S688Y mutation reduces Ca2+ influx through NMDARs and reduces NMDA-induced excitotoxicity in cultured hippocampal neurons. These findings provide key insights into the molecular mechanisms that underlie the regulation of NMDAR subtypes containing pathogenic mutations.
Bioanalysis of doxorubicin aglycone metabolites in human plasma samples–implications for doxorubicin drug monitoring
Authors: Siebel Christian , Lanvers-Kaminsky Claudia , Würthwein Gudrun , Hempel Georg , Boos Joachim 
Published: October 2020

AbstractThe widespread clinical use of the cytostatic doxorubicin together with the induction of chronic cardiomyopathy necessitates the conduct of further pharmacokinetic trials. Novel analytical technologies suitable for point-of-care applications can facilitate drug level analyses but might be prone to interferences from structurally similar compounds. Besides the alcohol metabolite doxorubicinol, aglycone metabolites of doxorubicin might affect its determination in plasma. To evaluate their analytical relevance, a validated HPLC method for the quantification of doxorubicin, doxorubicinol and four aglycones was used. The degradation pattern of doxorubicin in plasma under long-term storage was analysed with respect to the formation of aglycone products. In addition, overall 50 clinical samples obtained within the EPOC-MS-001-Doxo trial were analysed. Substantial degradation of doxorubicin in plasma occurred within a storage period of one year, but this did not lead to the formation of aglycones. In clinical samples, 7-deoxydoxorubicinolone was the major aglycone detectable in 35/50 samples and a concentration range of 1.0–12.7 µg L−1. If at all, the other aglycones were only determined in very low concentrations. Therefore, analytical interferences from aglycones seem to be unlikely with the exception of 7-deoxydoxorubicinolone whose concentration accounted for up to 65% of the doxorubicin concentration in the clinical samples analysed.
A comparative investigation of normal and inverted exchange bias effect for magnetic fluid hyperthermia applications
Authors: Tsopoe S. P. , Borgohain C. , Fopase Rushikesh , Pandey Lalit M. , Borah J. P. 
Published: October 2020

AbstractExchange bias (EB) of magnetic nanoparticles (MNPs) in the nanoscale regime has been extensively studied by researchers, which have opened up a novel approach in tuning the magnetic anisotropy properties of magnetic nanoparticles (MNPs) in prospective application of biomedical research such as magnetic hyperthermia. In this work, we report a comparative study on the effect of magnetic EB of normal and inverted core@shell (CS) nanostructures and its influence on the heating efficiency by synthesizing Antiferromagnetic (AFM) NiO (N) and Ferrimagnetic (FiM) Fe3O4 (F). The formation of CS structures for both systems is clearly authenticated by XRD and HRTEM analyses. The magnetic properties were extensively studied by Vibrating Sample Magnetometer (VSM). We reported that the inverted CS NiO@Fe3O4 (NF) MNPs have shown a greater EB owing to higher uncompensated spins at the interface of the AFM, in comparison to the normal CS Fe3O4@NiO (FN) MNPs. Both the CS systems have shown higher SAR values in comparison to the single-phased F owing to the EB coupling at the interface. However, the higher surface anisotropy of F shell with more EB field for NF enhanced the SAR value as compared to FN system. The EB coupling is hindered at higher concentrations of NF MNPs because of the enhanced dipolar interactions (agglomeration of nanoparticles). Both the CS systems reach to the hyperthermia temperature within 10 min. The cyto-compatibility analysis resulted in the excellent cell viability (> 75%) for 3 days in the presence of the synthesized NPs upto 1 mg/ml. These observations endorsed the suitability of CS nanoassemblies for magnetic fluid hyperthermia applications.
Capabilities of multi-pinhole SPECT with two stationary detectors for in vivo rat imaging
Authors: Janssen Jan P. , Hoffmann Jan V. , Kanno Takayuki , Nose Naoko , Grunz Jan-Peter , Onoguchi Masahisa , Chen Xinyu , Lapa Constantin , Buck Andreas K. , Higuchi Takahiro 
Published: October 2020

AbstractWe aimed to investigate the image quality of the U-SPECT5/CT E-Class a micro single-photon emission computed tomography (SPECT) system with two large stationary detectors for visualization of rat hearts and bones using clinically available 99mTc-labelled tracers. Sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR) of the small-animal SPECT scanner were investigated in phantom studies using an ultra-high-resolution rat and mouse multi-pinhole collimator (UHR-RM). Point source, hot-rod, and uniform phantoms with 99mTc-solution were scanned for high-count performance assessment and count levels equal to animal scans, respectively. Reconstruction was performed using the similarity-regulated ordered-subsets expectation maximization (SROSEM) algorithm with Gaussian smoothing. Rats were injected with ~ 100 MBq [99mTc]Tc-MIBI or ~ 150 MBq [99mTc]Tc-HMDP and received multi-frame micro-SPECT imaging after tracer distribution. Animal scans were reconstructed for three different acquisition times and post-processed with different sized Gaussian filters. Following reconstruction, CNR was calculated and image quality evaluated by three independent readers on a five-point scale from 1 = “very poor” to 5 = “very good”. Point source sensitivity was 567 cps/MBq and radioactive rods as small as 1.2 mm were resolved with the UHR-RM collimator. Collimator-dependent uniformity was 55.5%. Phantom CNR improved with increasing rod size, filter size and activity concentration. Left ventricle and bone structures were successfully visualized in rat experiments. Image quality was strongly affected by the extent of post-filtering, whereas scan time did not have substantial influence on visual assessment. Good image quality was achieved for resolution range greater than 1.8 mm in bone and 2.8 mm in heart. The recently introduced small animal SPECT system with two stationary detectors and UHR-RM collimator is capable to provide excellent image quality in heart and bone scans in a rat using standardized reconstruction parameters and appropriate post-filtering. However, there are still challenges in achieving maximum system resolution in the sub-millimeter range with in vivo settings under limited injection dose and acquisition time.
Modified aptamers as reagents to characterize recombinant human erythropoietin products
Authors: Jankowski Wojciech , Lagassé H. A. Daniel , Chang William C. , McGill Joseph , Jankowska Katarzyna I. , Gelinas Amy D. , Janjic Nebojsa , Sauna Zuben E. 
Published: October 2020

AbstractReliable and reproducible monitoring of the conformational state of therapeutic protein products remains an unmet technological need. This need is amplified by the increasing number of biosimilars entering the drug development pipeline as many branded biologics are reaching the end of their market exclusivity period. Availability of methods to better characterize protein conformation may improve detection of counterfit and unlicensed therapeutic proteins. In this study, we report the use of a set of modified DNA aptamers with enhanced chemical diversity to probe the conformational state of 12 recombinant human erythropoietin (rHuEPO) therapeutic protein products; one FDA-licensed rHuEPO originator biological product, three rHuEPO products that are approved for marketing in the US or EU as biosimilars, and eight rHuEPO products that are not approved for marketing in the US or EU. We show that several of these modified aptamers are able to distinguish rHuEPO reference products or approved biosimilars from non-licensed rHuEPO products on the basis of differences in binding kinetics and equilibrium affinity constants. These reagents exhibit sensitivity to the conformational integrity of various forms of rHuEPO and as such represent powerful, simple-to-use analytical tools to monitor the conformational integrity of therapeutic-proteins during manufacture and to screen for and identify both substandard and counterfeit products.