bluuebunny/crossref_metadata_2025_split huggingface dataset:
An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between cats
Authors: Langereis Martijn A. , Albulescu Irina C. , Stammen-Vogelzangs Judith , Lambregts Morindy , Stachura Ken , Miller Suzan , Bosco-Lauth Angela M. , Hartwig Airn E. , Porter Stephanie M. , Allen Michelle , Mogler Mark , van Kuppeveld Frank J. M. , Bosch Berend-Jan , Vermeij Paul , de Groof Ad , Bowen Richard A. , Davis Randy , Xu Zach , Tarpey Ian 
Published: October 2021

AbstractEarly in the SARS-CoV-2 pandemic concerns were raised regarding infection of new animal hosts and the effect on viral epidemiology. Infection of other animals could be detrimental by causing clinical disease, allowing further mutations, and bares the risk for the establishment of a non-human reservoir. Cats were the first reported animals susceptible to natural and experimental infection with SARS-CoV-2. Given the concerns these findings raised, and the close contact between humans and cats, we aimed to develop a vaccine candidate that could reduce SARS-CoV-2 infection and in addition to prevent spread among cats. Here we report that a Replicon Particle (RP) vaccine based on Venezuelan equine encephalitis virus, known to be safe and efficacious in a variety of animal species, could induce neutralizing antibody responses in guinea pigs and cats. The design of the SARS-CoV-2 spike immunogen was critical in developing a strong neutralizing antibody response. Vaccination of cats was able to induce high neutralizing antibody responses, effective also against the SARS-CoV-2 B.1.1.7 variant. Interestingly, in contrast to control animals, the infectious virus could not be detected in oropharyngeal or nasal swabs of vaccinated cats after SARS-CoV-2 challenge. Correspondingly, the challenged control cats spread the virus to in-contact cats whereas the vaccinated cats did not transmit the virus. The results show that the RP vaccine induces protective immunity preventing SARS-CoV-2 infection and transmission. These data suggest that this RP vaccine could be a multi-species vaccine useful to prevent infection and spread to and between animals should that approach be required.
Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens
Authors: Castaño-Bonilla Tamara , Alonso-Dominguez Juan M. , Barragán Eva , Rodríguez-Veiga Rebeca , Sargas Claudia , Gil Cristina , Chillón Carmen , Vidriales María B. , García Raimundo , Martínez-López Joaquín , Ayala Rosa , Larrayoz María J. , Anguita Eduardo , Cuello Rebeca , Cantalapiedra Alberto , Carrillo Estrella , Soria-Saldise Elena , Labrador Jorge , Recio Isabel , Algarra Lorenzo , Rodríguez-Medina Carlos , Bilbao-Syeiro Cristina , López-López Juan A. , Serrano Josefina , De Cabo Erik , Sayas María J. , Olave María T. , Sánchez-García Joaquín , Mateos Mamen , Blas Carlos , López-Lorenzo Jose L. , Lainez-Gonzalez Daniel , Serrano Juana , Martínez-Cuadrón David , Sanz Miguel A. , Montesinos Pau 
Published: October 2021

AbstractFLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability.
Dynamic FRET-FLIM based screening of signal transduction pathways
Authors: Harkes Rolf , Kukk Olga , Mukherjee Sravasti , Klarenbeek Jeffrey , van den Broek Bram , Jalink Kees 
Published: October 2021

AbstractFluorescence Lifetime Imaging (FLIM) is an intrinsically quantitative method to screen for protein–protein interactions and is frequently used to record the outcome of signal transduction events. With new highly sensitive and photon efficient FLIM instrumentation, the technique also becomes attractive to screen, with high temporal resolution, for fast changes in Förster Resonance Energy Transfer (FRET), such as those occurring upon activation of cell signaling. The second messenger cyclic adenosine monophosphate (cAMP) is rapidly formed following activation of certain cell surface receptors. cAMP is subsequently degraded by a set of phosphodiesterases (PDEs) which display cell-type specific expression and may also affect baseline levels of the messenger. To study which specific PDEs contribute most to cAMP regulation, we knocked down individual PDEs and recorded breakdown rates of cAMP levels following transient stimulation in HeLa cells stably expressing the FRET/FLIM sensor, Epac-SH189. Many hundreds of cells were recorded at 5 s intervals for each condition. FLIM time traces were calculated for every cell, and decay kinetics were obtained. cAMP clearance was significantly slower when PDE3A and, to a lesser amount, PDE10A were knocked down, identifying these isoforms as dominant in HeLa cells. However, taking advantage of the quantitative FLIM data, we found that knockdown of individual PDEs has a very limited effect on baseline cAMP levels. By combining photon-efficient FLIM instrumentation with optimized sensors, systematic gene knockdown and an automated open-source analysis pipeline, our study demonstrates that dynamic screening of transient cell signals has become feasible. The quantitative platform described here provides detailed kinetic analysis of cellular signals in individual cells with unprecedented throughput.
Azimuthal modulation of electromagnetically induced grating using structured light
Authors: Asadpour Seyyed Hossein , Kirova Teodora , Qian Jing , Hamedi Hamid R. , Juzeliūnas Gediminas , Paspalakis Emmanuel 
Published: October 2021

AbstractWe propose a theoretical scheme for creating a two-dimensional Electromagnetically Induced Grating in a three-level $$\Lambda $$
Λ
-type atomic system interacting with a weak probe field and two simultaneous position-dependent coupling fields—a two dimensional standing wave and an optical vortex beam. Upon derivation of the Maxwell wave equation, describing the dynamic response of the probe light in the atomic medium, we perform numerical calculations of the amplitude, phase modulations and Fraunhofer diffraction pattern of the probe field under different system parameters. We show that due to the azimuthal modulation of the Laguerre–Gaussian field, a two-dimensional asymmetric grating is observed, giving an increase of the zeroth and high orders of diffraction, thus transferring the probe energy to the high orders of direction. The asymmetry is especially seen in the case of combining a resonant probe with an off-resonant standing wave coupling and optical vortex fields. Unlike in previously reported asymmetric diffraction gratings for PT symmetric structures, the parity time symmetric structure is not necessary for the asymmetric diffraction grating presented here. The asymmetry is due to the constructive and destructive interference between the amplitude and phase modulations of the grating system, resulting in complete blocking of the diffracted photons at negative or positive angles, due to the coupling of the vortex beam. A detailed analysis of the probe field energy transfer to different orders of diffraction in the case of off-resonant standing wave coupling field proves the possibility of direct control over the performance of the grating.
Comparative evaluation of Nanopore polishing tools for microbial genome assembly and polishing strategies for downstream analysis
Authors: Lee Jin Young , Kong Minyoung , Oh Jinjoo , Lim JinSoo , Chung Sung Hee , Kim Jung-Min , Kim Jae-Seok , Kim Ki-Hwan , Yoo Jae-Chan , Kwak Woori 
Published: October 2021

AbstractAssembling high-quality microbial genomes using only cost-effective Nanopore long-read systems such as Flongle is important to accelerate research on the microbial genome and the most critical point for this is the polishing process. In this study, we performed an evaluation based on BUSCO and Prokka gene prediction in terms of microbial genome assembly for eight state-of-the-art Nanopore polishing tools and combinations available. In the evaluation of individual tools, Homopolish, PEPPER, and Medaka demonstrated better results than others. In combination polishing, the second round Homopolish, and the PEPPER × medaka combination also showed better results than others. However, individual tools and combinations have specific limitations on usage and results. Depending on the target organism and the purpose of the downstream research, it is confirmed that there remain some difficulties in perfectly replacing the hybrid polishing carried out by the addition of a short-read. Nevertheless, through continuous improvement of the protein pores, related base-calling algorithms, and polishing tools based on improved error models, a high-quality microbial genome can be achieved using only Nanopore reads without the production of additional short-read data. The polishing strategy proposed in this study is expected to provide useful information for assembling the microbial genome using only Nanopore reads depending on the target microorganism and the purpose of the research.
Alkyl-Quinolones derivatives as potential biomarkers for Pseudomonas aeruginosa infection chronicity in Cystic Fibrosis
Authors: Michalet Serge , Allard Pierre-Marie , Commun Carine , Ngoc Van Thanh Nguyen , Nouwade Kodjo , Gioia Bruna , Dijoux-Franca Marie-Geneviève , Wolfender Jean-Luc , Doléans-Jordheim Anne 
Published: October 2021

AbstractIn Cystic Fibrosis (CF), a rapid and standardized definition of chronic infection would allow a better management of Pseudomonas aeruginosa (Pa) infections, as well as a quick grouping of patients during clinical trials allowing better comparisons between studies. With this purpose, we compared the metabolic profiles of 44 in vitro cultures of Pa strains isolated from CF patients at different stages of infection in order to identify metabolites differentially synthetized according to these clinical stages. Compounds produced and secreted by each strain in the supernatant of a liquid culture were analysed by metabolomic approaches (UHPLC-DAD-ESI/QTOF, UV and UPLC-Orbitrap, MS). Multivariate analyses showed that first colonization strains could be differentiated from chronic colonization ones, by producing notably more Alkyl-Quinolones (AQs) derivatives. Especially, five AQs were discriminant: HQC5, HQNOC7, HQNOC7:1, db-PQS C9 and HQNOC9:1. However, the production of HHQ was equivalent between strain types. The HHQ/HQNOC9:1 ratio was then found to be significantly different between chronic and primo-colonising strains by using both UV (p = 0.003) and HRMS data (p = 1.5 × 10–5). Our study suggests that some AQ derivatives can be used as biomarkers for an improved management of CF patients as well as a better definition of the clinical stages of Pa infection.
A numerical study on the effect of CO2 addition for methane explosion reaction kinetics in confined space
Authors: Wang Jingyan , Liang Yuntao , Tian Fuchao , Chen Chengfeng 
Published: October 2021

AbstractTo explore the influence of the CO2 volume fraction on methane explosion in confined space over wide equivalent ratios, the explosion temperature, the explosion pressure, the concentration of the important free radicals, and the concentration of the catastrophic gas generated after the explosion in confined space were studied. Meanwhile, the elementary reaction steps dominating the gas explosion were identified through the sensitivity analysis. With the increase of the CO2 volume fraction, the explosion time prolongs, and the explosion pressure and temperature decrease monotonously. Moreover, the concentrations of the investigated free radicals also decrease as the increase of the CO2 volume fraction. For the catastrophic gas, the concentration of the gas product CO increases and the concentrations of CO2, NO, and NO2 decrease as the volume fraction of CO2 increases. When 7% methane is added with 10% CO2, the increase rate of CO is 76%, and the decrease rates of CO2, NO, and NO2 are 27%, 37%, and 39%, respectively. If the volume fraction of CO2 is constant, the larger the volume fraction of methane in the blend gas, the greater the mole fraction of radical H and the lower the mole fraction of radical O. For radical OH, its mole fraction first increases, and then decreases with the location of peak value of 9.5%, while the CO concentration increases with the increase of the methane concentration. For all the investigated volume fraction of methane, the addition of CO2 reduces the sensitivity coefficients of each key elementary reaction step, and the sensitivity coefficient of reaction promoting methane consumption decreases faster than that of the reaction inhibit methane consumption, which indicates that the addition of CO2 effectively suppresses the methane explosion.
Mice lacking DYRK2 exhibit congenital malformations with lung hypoplasia and altered Foxf1 expression gradient
Authors: Yogosawa Satomi , Ohkido Makiko , Horii Takuro , Okazaki Yasumasa , Nakayama Jun , Yoshida Saishu , Toyokuni Shinya , Hatada Izuho , Morimoto Mitsuru , Yoshida Kiyotsugu 
Published: October 2021

AbstractCongenital malformations cause life-threatening diseases in pediatrics, yet the molecular mechanism of organogenesis is poorly understood. Here we show that Dyrk2-deficient mice display congenital malformations in multiple organs. Transcriptome analysis reveals molecular pathology of Dyrk2-deficient mice, particularly with respect to Foxf1 reduction. Mutant pups exhibit sudden death soon after birth due to respiratory failure. Detailed analyses of primordial lungs at the early developmental stage demonstrate that Dyrk2 deficiency leads to altered airway branching and insufficient alveolar development. Furthermore, the Foxf1 expression gradient in mutant lung mesenchyme is disrupted, reducing Foxf1 target genes, which are necessary for proper airway and alveolar development. In ex vivo lung culture system, we rescue the expression of Foxf1 and its target genes in Dyrk2-deficient lung by restoring Shh signaling activity. Taken together, we demonstrate that Dyrk2 is essential for embryogenesis and its disruption results in congenital malformation.
Diffusive skin effect and topological heat funneling
Authors: Cao Pei-Chao , Li Ying , Peng Yu-Gui , Qi Minghong , Huang Wen-Xi , Li Peng-Qi , Zhu Xue-Feng 
Published: October 2021

AbstractNon-Hermitian wave system has attracted intense attentions in the past decade since it reveals interesting physics and generates various counterintuitive effects. However, in the diffusive system that is inherently non-Hermitian with natural dissipation, the robust control of heat flow is hitherto still a challenge. Here we introduce the skin effect into diffusive systems. Different from the skin effect in wave systems, where asymmetric couplings were enabled by dynamic modulations or judicious gain/loss engineering, asymmetric couplings of the temperature fields in diffusive systems can be realized by directly contacted metamaterial channels. Topological heat funneling is further presented, where the temperature field automatically concentrates towards a designated position and shows a strong immunity against the defects. Our work indicates that the diffusive system can provide a distinctive platform for exploring non-Hermitian physics as well as thermal topology.
Updates in deep learning research in ophthalmology
Authors: Ng Wei Yan , Zhang Shihao , Wang Zhaoran , Ong Charles Jit Teng , Gunasekeran Dinesh V. , Lim Gilbert Yong San , Zheng Feihui , Tan Shaun Chern Yuan , Tan Gavin Siew Wei , Rim Tyler Hyungtaek , Schmetterer Leopold , Ting Daniel Shu Wei 
Published: October 2021

Abstract
Ophthalmology has been one of the early adopters of artificial intelligence (AI) within the medical field. Deep learning (DL), in particular, has garnered significant attention due to the availability of large amounts of data and digitized ocular images. Currently, AI in Ophthalmology is mainly focused on improving disease classification and supporting decision-making when treating ophthalmic diseases such as diabetic retinopathy, age-related macular degeneration (AMD), glaucoma and retinopathy of prematurity (ROP). However, most of the DL systems (DLSs) developed thus far remain in the research stage and only a handful are able to achieve clinical translation. This phenomenon is due to a combination of factors including concerns over security and privacy, poor generalizability, trust and explainability issues, unfavorable end-user perceptions and uncertain economic value. Overcoming this challenge would require a combination approach. Firstly, emerging techniques such as federated learning (FL), generative adversarial networks (GANs), autonomous AI and blockchain will be playing an increasingly critical role to enhance privacy, collaboration and DLS performance. Next, compliance to reporting and regulatory guidelines, such as CONSORT-AI and STARD-AI, will be required to in order to improve transparency, minimize abuse and ensure reproducibility. Thirdly, frameworks will be required to obtain patient consent, perform ethical assessment and evaluate end-user perception. Lastly, proper health economic assessment (HEA) must be performed to provide financial visibility during the early phases of DLS development. This is necessary to manage resources prudently and guide the development of DLS.
Spectral Modulation Detection Performance and Speech Perception in Pediatric Cochlear Implant Recipients
Authors: Davidson Lisa S. , Geers Ann E. , Uchanski Rosalie M. 
Published: October 2021

Purpose:
The aims of this study were, for pediatric cochlear implant (CI) recipients, (a) to determine the effect of age on their spectral modulation detection (SMD) ability and compare their age effect to that of their typically hearing (TH) peers; (b) to identify demographic, cognitive, and audiological factors associated with SMD ability; and (c) to determine the unique contribution of SMD ability to segmental and suprasegmental speech perception performance.

Method:
A total of 104 pediatric CI recipients and 38 TH peers (ages 6–11 years) completed a test of SMD. CI recipients completed tests of segmental (e.g., word recognition in noise and vowels and consonants in quiet) and suprasegmental (e.g., talker discrimination, stress discrimination, and emotion identification) perception, nonverbal intelligence, and working memory. Regressions analyses were used to examine the effects of group and age on percent-correct SMD scores. For the CI group, the effects of demographic, audiological, and cognitive variables on SMD performance and the effects of SMD on speech perception were examined.

Results:
The TH group performed significantly better than the CI group on SMD. Both groups showed better performance with increasing age. Significant predictors of SMD performance for the CI group were age and nonverbal intelligence. SMD performance predicted significant variance in segmental and suprasegmental perception. The variance predicted by SMD performance was nearly double for suprasegmental than for segmental perception.

Conclusions:
Children in the CI group, on average, scored lower than their TH peers. The slopes of improvement in SMD with age did not differ between the groups. The significant effect of nonverbal intelligence on SMD performance in CI recipients indicates that difficulties inherent in the task affect outcomes. SMD ability predicted speech perception scores, with a more prominent role in suprasegmental than in segmental speech perception. SMD ability may provide a useful nonlinguistic tool for predicting speech perception benefit, with cautious interpretation based on age and cognitive function.
Gängige veterinärmedizinische Praxis in der Kleintieranästhesie – eine Onlineumfrage unter Kleintierpraktikern in Europa
Authors: Reiser Kathrin , Schroers Maike , Reese Sven , Meyer-Lindenberg Andrea 
Published: October 2021

Zusammenfassung
Gegenstand und Ziel Erhebung des Standes der Kleintieranästhesie in Europa und Überprüfung der Möglichkeit zur Einhaltung der Leitlinien der AVA (American Society of Anesthesiologists) und der DVG-Fachgruppe VAINS (Veterinärmedizinische Anästhesie, Intensivmedizin, Notfallmedizin und Schmerztherapie).
Material und Methoden Ein Link zu einer Onlineumfrage mit Fragen zum Narkosemanagement (Themenbereiche Demografie, Ausstattung, Monitoring, Wärmemanagement, präanästhetische Untersuchung, Narkoseprotokoll u. a.) wurde an Kleintierpraktiker in verschiedenen Ländern verschickt.
Ergebnisse Die 767 eingegangenen auswertbaren Fragebögen stammten aus Deutschland (n = 343), Österreich (n = 216), Schweiz (n = 83), Großbritannien (n = 38), Frankreich (n = 25), Ungarn (n = 25), Skandinavien (n = 23) und „sonstigen Ländern“ (n = 11). Durchschnittlich 91 % der Befragten erfüllten die Leitlinie der AVA und 58 % die Leitlinie der Fachgruppe VAINS noch vor deren Veröffentlichung. Praxen/Kliniken mit mehr Mitarbeiten hatten eine bessere Ausstattung und Praxen/Kliniken mit mehr Anästhesien pro Woche führten häufiger eine „gute Voruntersuchung“ durch.
Schlussfolgerung und klinische Relevanz Obwohl die Leitlinien z. T. erfüllt werden, ließ sich zeigen, dass in vielen Praxen/Kliniken das Narkoseregime optimiert werden kann, u. a. durch Verbesserung der Ausstattung oder deren bessere Nutzung.
Akutes Leberversagen bei einem Hund nach Aufnahme eines Pilzes, vermutlich der Gattung Amanita
Authors: Runft Sandra , Mischke Reinhard , Hoppe Sonja , Hewicker-Trautwein Marion 
Published: October 2021

ZusammenfassungEin 4 Jahre alter, männlich-kastrierter, 29,4 kg schwerer Husky-Mischling, der am Tag zuvor einen Pilz, wahrscheinlich der Gattung Amanita. gefressen hatte, wurde mit Diarrhö, Vomitus, Inappetenz und zunehmender Apathie vorgestellt. Labordiagnostisch ließen sich Hypoglykämie, Hyperbilirubinämie, erhöhte Leberenzymaktivitäten sowie verminderte Gerinnungsfaktoraktivitäten (veränderte Prothrombinzeit und aktivierte partielle Thromboplastinzeit) feststellen. Trotz stationärer symptomatischer Therapie über 3 Tage verschlechterte sich das Allgemeinbefinden des Hundes und er wurde euthanasiert. Die pathomorphologischen Befunde waren durch Blutungen in mehreren Organen, blutige Ingesta, Ikterus und hochgradige Leberzellnekrosen gekennzeichnet.