bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myelination of parvalbumin interneurons shapes the function of cortical sensory inhibitory circuits
Authors: Benamer Najate , Vidal Marie , Balia Maddalena , Angulo María Cecilia 
Published: October 2020

AbstractMyelination of projection neurons by oligodendrocytes is key to optimize action potential conduction over long distances. However, a large fraction of myelin enwraps the axons of parvalbumin-positive fast-spiking interneurons (FSI), exclusively involved in local cortical circuits. Whether FSI myelination contributes to the fine‐tuning of intracortical networks is unknown. Here we demonstrate that FSI myelination is required for the establishment and maintenance of the powerful FSI-mediated feedforward inhibition of cortical sensory circuits. The disruption of GABAergic synaptic signaling of oligodendrocyte precursor cells prior to myelination onset resulted in severe FSI myelination defects characterized by longer internodes and nodes, aberrant myelination of branch points and proximal axon malformation. Consequently, high-frequency FSI discharges as well as FSI-dependent postsynaptic latencies and strengths of excitatory neurons were reduced. These dysfunctions generated a strong excitation-inhibition imbalance that correlated with whisker-dependent texture discrimination impairments. FSI myelination is therefore critical for the function of mature cortical inhibitory circuits.
Gap between pediatric and adult approvals of molecular targeted drugs
Authors: Nishiwaki Satoshi , Ando Yuichi 
Published: October 2020

AbstractTo clarify the approval status of molecular targeted antineoplastic drugs in the United States (U.S.), the European Union (E.U.), and Japan (JP), we checked the status of pediatric indications according to the package insert of each drug. A total of 103 drugs were approved for adult patients in at least one of the three regions whereas only 19 drugs were approved for pediatric patients. Sixty-six of 103 drugs (64.1%) had adult indications in the U.S., the E.U., and JP, whereas only three drugs had pediatric indications in all three regions. Abnormalities in six genes (NRAS, ABL1, JAK2, KIT, ALK and BRAF) were common in childhood cancers as well as adult cancers, for which at least one approved drug could be a potentially actionable drug. Although there were 16 candidate drugs that had adult indications for these abnormalities, only three drugs (18.8%) had pediatric indications. We confirmed that there were few molecular targeted antineoplastic drugs with pediatric indications in the U.S., the E.U., and JP compared with the number of approved drugs for adults. Drugs targeting genomic abnormalities which were common in both adult and pediatric cancers were considered to be good candidates for expansion of their indication for pediatric patients.
Lead (Pb) bioaccumulation and antioxidative responses in Tetraena qataranse
Authors: Usman Kamal , Abu-Dieyeh Mohammed H. , Zouari Nabil , Al-Ghouti Mohammad A. 
Published: October 2020

AbstractLead (Pb) is the second most toxic metal on Earth and is toxic to humans and other living things. In plants, Pb commonly inhibits growth when it is at a concentration in the soil of 30 mg/kg or more but several Pb tolerant plants have been reported. However, few studies have focused on plant response to Pb exposure, particularly at concentrations higher than 30 mg/kg. The assessment and evaluation of metal dose-dependent plant responses will assist in future phytoremediation studies. Therefore, this work documents the Pb concentration-dependent antioxidative response in Tetraena qataranse. Young seedlings were irrigated with 0, 25, 50, and 100 mg/L Pb every 48 h for seven weeks under greenhouse conditions. A phytotoxicity test showed that at the lowest treatment concentration, Pb stimulates growth. However, at 100 mg/L (1600 mg/kg Pb in the growth medium at harvest), the metal disrupted healthy growth in T. qataranse, particularly root development. Metal accumulation in the root was higher (up to 2784 mg/kg) than that of the shoot (1141.6 mg/kg). Activity assays of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), and glutathione reductase (GR) showed a progressive increase in enzymatic activities due to Pb treatment. Together, the results of this study suggest that T. qataranse is a Pb hyperaccumulator. Increased antioxidant enzyme activity was essential to maintaining cellular homeostasis and assisted in the arid plant’s tolerance to Pb stress.
The metabolic footprint of compromised insulin sensitivity under fasting and hyperinsulinemic-euglycemic clamp conditions in an Arab population
Authors: Halama Anna , Suleiman Noor N. , Kulinski Michal , Bettahi Ilham , Hassoun Shaimaa , Alkasem Meis , Abdalhakam Ibrahem , Iskandarani Ahmad , Samra Tareq A. , Atkin Stephen L. , Suhre Karsten , Abou-Samra Abdul Badi 
Published: October 2020

AbstractMetabolic pathways that are corrupted at early stages of insulin resistance (IR) remain elusive. This study investigates changes in body metabolism in clinically healthy and otherwise asymptomatic subjects that may become apparent already under compromised insulin sensitivity (IS) and prior to IR. 47 clinically healthy Arab male subjects with a broad range of IS, determined by hyperinsulinemic-euglycemic clamp (HIEC), were investigated. Untargeted metabolomics and complex lipidomics were conducted on serum samples collected under fasting and HIEC conditions. Linear models were used to identify associations between metabolites concentrations and IS levels. Among 1896 identified metabolites, 551 showed significant differences between fasting and HIEC, reflecting the metabolic switch in energy utilization. At fasting, 336 metabolites, predominantly di- and tri-acylglycerols, showed significant differences between subjects with low and high levels of IS. Changes in amino acid, carbohydrate and fatty acid metabolism in response to insulin were impaired in subjects with low IS. Association of altered mannose and amino acids with IS was also replicated in an independent cohort of T2D patients. We identified metabolic phenotypes that characterize clinically healthy Arab subjects with low levels of IS at their fasting state. Our study is providing further insights into the metabolic pathways that precede IR.
Perceiving amputee gait from biological motion: kinematics cues and effect of experience level
Authors: Lee I.-Chieh , Pacheco Matheus M. , Lewek Michael D. , Huang He 
Published: October 2020

AbstractPhysical therapists (PT) and clinicians must be skilled in identifying gait features through observation to assess motor deficits in patients and intervene appropriately. Inconsistent results in the literature have led researchers to question how clinical experience influences PT’s gait perception and to seek the key kinematic features that should be trained to enhance PT’s skill. Thus, this study investigated (1) what are the informative kinematic features that allow gait-deviation perception in amputee gait and (2) whether there are differences in observational gait skills between PT and individuals with less clinical experience (PT students [PTS] and Novices). We introduced a new method that combines biological motion and principal component analysis to gradually mesh amputee and typical walking patterns. Our analysis showed that on average the accuracy rate in identifying gait deviations between PT and PTS was similar and better than Novices. Also, we found that PT’s experience was demonstrated by their better perception of gait asymmetry. The extracted principal components demonstrated that the major gait deviation of amputees was the medial–lateral body sway and spatial gait asymmetry.
Ectothermy and cardiac shunts profoundly slow the equilibration of inhaled anaesthetics in a multi-compartment model
Authors: Williams Catherine J. A. , Malte Christian Lind , Malte Hans , Bertelsen Mads F. , Wang Tobias 
Published: October 2020

AbstractThe use of inhalational anaesthesia is ubiquitous in terrestrial vertebrates. Given the dependence of these agents on delivery by the cardiorespiratory system, we developed a new computational model predicting equilibration of inhaled anaesthetics in mammalian and ectotherm conditions including the ability of reptiles to maintain vascular shunts. A multi-compartment model was constructed from simultaneously-solved equations, verified by comparison to the literature for endo and ectotherm physiology. The time to 90% equilibration of anaesthetic in arterial blood (t90) is predicted and used to compare anaesthetics and physiologies. The five to tenfold lower cardiac output and minute ventilation of ectothermic vertebrates is predicted to slow equilibration times by five to ten times leading to 90% equilibration in ectotherm arterial blood of over 200 min, compounded by reduction in body temperature, and the extent of right-to-left vascular shunts. The impact of these findings is also influenced by the solubility coefficient of the anaesthetic, such that at net right-to-left shunt fractions of over 0.8, sevoflurane loses the advantage of faster equilibration, in comparison with isoflurane. We explore clinical strategies to regulate anaesthetic uptake in ectotherms by managing convectional flow especially by supportive ventilation and reduction of the right-to-left shunt.
Spirochetes isolated from arthropods constitute a novel genus Entomospira genus novum within the order Spirochaetales
Authors: Graña-Miraglia Lucía , Sikutova Silvie , Vancová Marie , Bílý Tomáš , Fingerle Volker , Sing Andreas , Castillo-Ramírez Santiago , Margos Gabriele , Rudolf Ivo 
Published: October 2020

AbstractSpirochetal bacteria were successfully isolated from mosquitoes (Culex pipiens, Aedes cinereus) in the Czech Republic between 1999 and 2002. Preliminary 16S rRNA phylogenetic sequence analysis showed that these strains differed significantly from other spirochetal genera within the family Spirochaetaceae and suggested a novel bacterial genus in this family. To obtain more comprehensive genomic information of these isolates, we used Illumina MiSeq and Oxford Nanopore technologies to sequence four genomes of these spirochetes (BR151, BR149, BR193, BR208). The overall size of the genomes varied between 1.68 and 1.78 Mb; the GC content ranged from 38.5 to 45.8%. Draft genomes were compared to 36 publicly available genomes encompassing eight genera from the class Spirochaetes. A phylogeny generated from orthologous genes across all taxa and the percentage of conserved proteins (POCP) confirmed the genus status of these novel spirochetes. The genus Entomospira gen. nov. is proposed with BR151 selected as type species of the genus. For this isolate and the closest related isolate, BR149, we propose the species name Entomospira culicis sp. nov. The two other isolates BR208 and BR193 are named Entomospira nematocera sp. nov. (BR208) and Entomospira entomophilus sp. nov. (BR193). Finally, we discuss their interesting phylogenetic positioning.
Investigating the effects of transcranial alternating current stimulation on primary somatosensory cortex
Authors: Manzo Nicoletta , Guerra Andrea , Giangrosso Margherita , Belvisi Daniele , Leodori Giorgio , Berardelli Alfredo , Conte Antonella 
Published: October 2020

AbstractNear-threshold tactile stimuli perception and somatosensory temporal discrimination threshold (STDT) are encoded in the primary somatosensory cortex (S1) and largely depend on alpha and beta S1 rhythm. Transcranial alternating current stimulation (tACS) is a non-invasive neurophysiological technique that allows cortical rhythm modulation. We investigated the effects of tACS delivered over S1 at alpha, beta, and gamma frequencies on near-threshold tactile stimuli perception and STDT, as well as phase-dependent tACS effects on near-threshold tactile stimuli perception in healthy subjects. In separate sessions, we tested the effects of different tACS montages, and tACS at the individualised S1 μ-alpha frequency peak, on STDT and near-threshold tactile stimuli perception. We found that tACS applied over S1 at alpha, beta, and gamma frequencies did not modify STDT or near-threshold tactile stimuli perception. Moreover, we did not detect effects of tACS phase or montage. Finally, tACS did not modify near-threshold tactile stimuli perception and STDT even when delivered at the individualised μ-alpha frequency peak. Our study showed that tACS does not alter near-threshold tactile stimuli or STDT, possibly due to the inability of tACS to activate deep S1 layers. Future investigations may clarify tACS effects over S1 in patients with focal dystonia, whose pathophysiology implicates increased STDT.
Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats
Authors: Chaccour Carlos , Abizanda Gloria , Irigoyen-Barrio Ángel , Casellas Aina , Aldaz Azucena , Martínez-Galán Fernando , Hammann Felix , Gil Ana Gloria 
Published: October 2020

AbstractIvermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80–90 mg/kg), higher dose (110–140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma and lungs was determined in all animals. There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 g/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean Cmax 86.2 ng/ml vs. 26.2 ng/ml in the lower dose group and 152 ng/ml vs. 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for low-dose females. nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.
PIK3CA mutation enrichment and quantitation from blood and tissue
Authors: Keraite Ieva , Alvarez-Garcia Virginia , Garcia-Murillas Isaac , Beaney Matthew , Turner Nicholas C. , Bartos Clare , Oikonomidou Olga , Kersaudy-Kerhoas Maïwenn , Leslie Nicholas R. 
Published: October 2020

AbstractPIK3CA is one of the two most frequently mutated genes in breast cancers, occurring in 30–40% of cases. Four frequent ‘hotspot’ PIK3CA mutations (E542K, E545K, H1047R and H1047L) account for 80–90% of all PIK3CA mutations in human malignancies and represent predictive biomarkers. Here we describe a PIK3CA mutation specific nuclease-based enrichment assay, which combined with a low-cost real-time qPCR detection method, enhances assay detection sensitivity from 5% for E542K and 10% for E545K to 0.6%, and from 5% for H1047R to 0.3%. Moreover, we present a novel flexible prediction method to calculate initial mutant allele frequency in tissue biopsy and blood samples with low mutant fraction. These advancements demonstrated a quick, accurate and simple detection and quantitation of PIK3CA mutations in two breast cancer cohorts (first cohort n = 22, second cohort n = 25). Hence this simple, versatile and informative workflow could be applicable for routine diagnostic testing where quantitative results are essential, e.g. disease monitoring subject to validation in a substantial future study.
Perinatal depression and anxiety of primipara is higher than that of multipara in Japanese women
Authors: Nakamura Yukako , Okada Takashi , Morikawa Mako , Yamauchi Aya , Sato Maya , Ando Masahiko , Ozaki Norio 
Published: October 2020

AbstractThe proportion of women who experience a depressive state after delivery differs between primiparas and multiparas, so it is important to clarify the different factors related to depression between the two groups. In this study, we confirmed the differences in depressive states, the perinatal period, and social support between primiparas and multiparas, and clarified their characteristics. Data were extracted from a prospective cohort questionnaire survey conducted on pregnant women in Japan that included sociodemographic questions, the Edinburgh Postnatal Depression Scale, and the Japanese version of the Social Support Questionnaire. We carried out the chi-square test, Student’s t-test, and analysis of covariance to compare responses between primiparas and multiparas. A total of 1138 primiparas and 380 multiparas provided valid responses. We found that primiparas had higher rates of experiencing maternity blues and postpartum depression than multiparas. We also found that primiparas had higher anxiety scores than multiparas. Primiparas with postpartum depression perceived a lower number of persons available to provide social support than primiparas without postpartum depression. These findings suggest that it is important to provide pregnant women, especially for primiparas, with information that allows them to increase the number of people who can provide them with support.
Metasurfaces for efficient digital noise absorption
Authors: Aihara Ryoya , Wakatsuchi Hiroki 
Published: October 2020

AbstractWe numerically demonstrate two types of metasurface absorbers to efficiently absorb digital signals. First, we show that the digital waveforms used in this study contain not only a fundamental wave but also nonnegligible harmonic waves, which limits the absorption performance of a conventional metasurface absorber operating in only a single, finite frequency band. The first type of the proposed absorbers is designed using two kinds of unit cells, each of which absorbs either a fundamental frequency or third harmonic of an incident digital waveform. This dual-band metasurface absorber exhibits absorption performance exceeding that of the conventional metasurface absorber and more strongly dissipates the energy of a digital waveform. In addition, the second type of absorber exploits the concept of nonlinear analogous circuits to convert an incoming wave to a different waveform, specifically, a triangular waveform that has a larger magnitude at a fundamental frequency. Therefore, the incoming waveform is more effectively absorbed by this waveform-conversion metasurface absorber as well. Although still there remain some issues to put these digital signal absorbers into practice, including experimental validation, our results contribute to mitigating electromagnetic interference issues caused by digital noise and realising physically smaller, lighter digital signal processing products for the next generation.
The influences of low protein diet on the intestinal microbiota of mice
Authors: Masuoka Hiroaki , Suda Wataru , Tomitsuka Eriko , Shindo Chie , Takayasu Lena , Horwood Paul , Greenhill Andrew R. , Hattori Masahira , Umezaki Masahiro , Hirayama Kazuhiro 
Published: October 2020

AbstractRecent research suggests that protein deficiency symptoms are influenced by the intestinal microbiota. We investigated the influence of low protein diet on composition of the intestinal microbiota through animal experiments. Specific pathogen-free (SPF) mice were fed one of four diets (3, 6, 9, or 12% protein) for 4 weeks (n = 5 per diet). Mice fed the 3% protein diet showed protein deficiency symptoms such as weight loss and low level of blood urea nitrogen concentration in their serum. The intestinal microbiota of mice in the 3% and 12% protein diet groups at day 0, 7, 14, 21 and 28 were investigated by 16S rRNA gene sequencing, which revealed differences in the microbiota. In the 3% protein diet group, a greater abundance of urease producing bacterial species was detected across the duration of the study. In the 12% diet protein group, increases of abundance of Streptococcaceae and Clostridiales families was detected. These results suggest that protein deficiency may be associated with shifts in intestinal microbiota.
Extraction of single serve coffee capsules: linking properties of ground coffee to extraction dynamics and cup quality
Authors: Eiermann André , Smrke Samo , Guélat Loïc-Marco , Wellinger Marco , Rahn Anja , Yeretzian Chahan 
Published: October 2020

AbstractThe objective of this paper is to elucidate the variables that govern coffee extraction from single serve coffee capsules. The study was conducted on 43 Nespresso and Nespresso-compatible capsules of the same geometry, from all of which the coffee was extracted on the same machine. This allowed the link between a range of coffee and capsule (input) parameters with coffee brew (output) variables to be studied. It was demonstrated that the most efficient way to increase total dissolved solids in the brew is to use more coffee for extraction, and/or to grind the coffee more finely. However, grinding too finely can lead to excessive flow restriction. The most significant new insight from this study is the importance of the proportion of fines (particles smaller than 100 µm) regarding the capsule extraction dynamics. Capsules with a higher share of fines, for similar median particle size of the ground coffee, led to longer extraction times. General rules applicable for capsule coffee product development were established, although fine-tuning of parameters for successful capsule coffee extraction remains specific to production line and type of coffee.
Asynchronous c-VEP communication tools—efficiency comparison of low-target, multi-target and dictionary-assisted BCI spellers
Authors: Gembler Felix W. , Benda Mihaly , Rezeika Aya , Stawicki Piotr R. , Volosyak Ivan 
Published: October 2020

AbstractKeyboards and smartphones allow users to express their thoughts freely via manual control. Hands-free communication can be realized with brain–computer interfaces (BCIs) based on code-modulated visual evoked potentials (c-VEPs). Various variations of such spellers have been developed: Low-target systems, multi-target systems and systems with dictionary support. In general, it is not clear which kinds of systems are optimal in terms of reliability, speed, cognitive load, and visual load. The presented study investigates the feasibility of different speller variations. 58 users tested a 4-target speller and a 32-target speller with and without dictionary functionality. For classification, multiple individualized spatial filters were generated via canonical correlation analysis (CCA). We used an asynchronous implementation allowing non-control state, thus aiming for high accuracy rather than speed. All users were able to control the tested spellers. Interestingly, no significant differences in accuracy were found: 94.4%, 95.5% and 94.0% for 4-target spelling, 32-target spelling, and dictionary-assisted 32-target spelling. The mean ITRs were highest for the 32-target interface: 45.2, 96.9 and 88.9 bit/min. The output speed in characters per minute, was highest in dictionary-assisted spelling: 8.2, 19.5 and 31.6 characters/min. According to questionnaire results, 86% of the participants preferred the 32-target speller over the 4-target speller.