bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of colony‐forming tissue stem cells in the macula flava of the human vocal fold in vivo
Authors: Sato Kiminori , Chitose Shun‐ichi , Sato Kiminobu , Sato Fumihiko , Ono Takeharu , Umeno Hirohito 
Published: March 2021

AbstractObjectivesOur previous investigations showed that tissue stem cells in the maculae flavae (a stem cell niche) form colonies in vivo like stem cells in vitro. However, the roles of colony‐forming cells in the maculae flavae in vivo have not yet been determined.This study investigated the metabolism of the colony‐forming tissue stem cells in the maculae flavae of the human adult vocal fold.Study designHistologic analysis of the human vocal folds.MethodsThree normal human adult vocal folds were investigated under transmission electron microscopy and light microscopy including immunohistochemistry.ResultsMitochondrial cristae of the colony‐forming cells in the maculae flavae were sparse. Hence, the microstructural features of the mitochondria suggested that their metabolic activity and oxidative phosphorylation were low. Colony‐forming cells strongly expressed glucose transporter‐1 and glycolytic enzymes (hexokinase II, glyceraldehyde‐3‐phosphate dehydrogenase and lactate dehydrogenase A). The colony‐forming cells did not express phosphofructokinase‐1 but did express glucose‐6‐phosphate dehydrogenase indicating the cells relied more on the pentose phosphate pathway. Since the colony‐forming cells expressed lactate dehydrogenase A, cells seemed to rely more on anaerobic glycolysis in an anaerobic microenvironment.ConclusionsThe present study is consistent with the hypothesis that the colony‐forming tissue stem cells in the maculae flavae of the human adult vocal fold seemed to rely more on anaerobic glycolysis using the pentose phosphate pathway for energy supply in vivo. Microstructural features of the mitochondria and expressed glycolytic enzymes of the colony‐forming cells in the maculae flavae suggested that the oxidative phosphorylation activity was low.In an anaerobic microenvironment in vivo, there is likely a complex cross‐talk regarding the metabolism between the colony‐forming aggregated cells along the adhesion machinery and chemical signaling pathways, which reduces toxic oxygen species and is favorable to maintaining the stemness and undifferentiated states of the tissue stem cells.Level of EvidenceNA.
On the matter of phytoplankton: A novel method using 3D computer models to calculate biovolume of microorganisms
Authors: Mohan Joseph , Saros Jasmine , Stone Jeffery R. 
Published: March 2021

AbstractWe develop a new method that allows for more accurate biovolume calculations of microorganisms. This method also allows the volume of individual skeletal features of microorganisms to be analyzed separately so that estimates of the resource cost per evolutionary adaptations may be assessed. We also provide a means to link community changes to alterations in nutrient cycles, ecosystem function, and rock‐forming processes by plankton. This method integrates computer‐aided design software from engineering and architecture into biological applications. Our method substantially improves the accuracy of biovolume estimates for species which currently rely upon simple geometric models that preclude the presence of ultrastructure in microorganism skeletons. In addition, using simple shapes to represent the skeletal form of microorganisms prohibits the exploration of resource cost that various adaptations, for example, spines for protection from grazers, have imposed upon plankton. Thus, integrating architectural and engineering approaches more broadly into biovolume estimations produces new insight into the physiology of microorganisms that can turn speculations into quantitative analyses.
Novel frameshift mutation in PURA gene causes severe encephalopathy of unclear cause
Authors: Spangenberg Lucía , Guecaimburú Rosario , Tapié Alejandra , Vivas Susana , Rodríguez Soledad , Graña Martín , Naya Hugo , Raggio Víctor 
Published: March 2021

AbstractBackgroundThe etiology of many genetic diseases is challenging. This is especially true for developmental disorders of the central nervous system, since several genes can be involved. Many of such pathologies are considered rare diseases, since they affect less than 1 in 2000 people. Due to their low frequency, they present several difficulties for patients, from the delay in the diagnosis to the lack of treatments. Next‐generation sequencing techniques have improved the search for diagnosis in several pathologies. Many studies have shown that the use of whole‐exome/genome sequencing in rare Mendelian diseases has a diagnostic yield between 30% and 50% depending on the disease.MethodsHere, we present the case of an undiagnosed 6‐year‐old boy with severe encephalopathy of unclear cause, whose etiological diagnosis was achieved by whole‐genome sequencing.ResultsWe found a novel variant that has not been previously reported in patients nor it has been described in GnomAD. Segregation analysis supports a de novo mutation, since it is not present in healthy parents. The change is predicted to be harmful to protein function, since it falls in the first quarter of the protein producing an altered reading frame and generating a premature stop codon. Additionally, the variant is classified as pathogenic according to ACMG criteria (PVS1, PM2, and PP3). Furthermore, there are several reported frameshift mutations in nearby codons as well as nonsense mutations that are predicted as pathogenic in other studies.ConclusionWe found a novel de novo frameshift mutation in the PURA gene (MIM number 600473), c.151_161del, with sufficient evidence of its pathogenicity.
Calibration‐free regional RF shims for MRS
Authors: Berrington Adam , Považan Michal , Mirfin Christopher , Bawden Stephen , Park Young Woo , Marsh Daniel C. , Bowtell Richard , Gowland Penny A. 
Published: March 2021

PurposeAchieving a desired RF transmit field () in small regions of interest is critical for single‐voxel MRS at ultrahigh field. Radio‐frequency (RF) shimming, using parallel transmission, requires mapping and optimization, which limits its ease of use. This work aimed to generate calibration‐free RF shims for predefined target regions of interest, which can be applied to any participant, to produce a desired absolute magnitude (||).MethodsThe RF shims were found offline by joint optimization on a database comprising maps from 11 subjects, considering regions of interest in occipital cortex, hippocampus and posterior cingulate, as well as whole brain. The || achieved was compared with a tailored shimming approach, and MR spectra were acquired using tailored and calibration‐free shims in 4 participants. Global and local 10g specific‐absorption‐rate deposition were estimated using Duke and Ella dielectric models.ResultsThere was no difference in the mean || produced using calibration‐free versus tailored RF shimming in the occipital cortex (p = .15), hippocampus (p = .5), or posterior cingulate (p = .98), although differences were observed in the RMS error ||. Spectra acquired using calibration‐free shims had similar SNR and low residual water signal. Under identical power settings, specific‐absorption‐rate deposition was lower compared with operating in quadrature mode. For example, the total head specific absorption rate was around 35% less for the occipital cortex.ConclusionThis work demonstrates that static RF shims, optimized offline for small regions, avoid the need for mapping and optimization for each region of interest and participant. Furthermore, power settings may be increased when using calibration‐free shims, to better take advantage of RF shimming.
Dynamic MRI of the abdomen using parallel non‐Cartesian convolutional recurrent neural networks
Authors: Zhang Yufei , She Huajun , Du Yiping P. 
Published: March 2021

PurposeTo improve the image quality and reduce computational time for the reconstruction of undersampled non‐Cartesian abdominal dynamic parallel MR data using the deep learning approach.MethodsAn algorithm of parallel non‐Cartesian convolutional recurrent neural networks (PNCRNNs) was developed to enable the use of the redundant information in both spatial and temporal domains, and achieve data fidelity for the reconstruction of non‐Cartesian parallel MR data. The performance of PNCRNNs was evaluated for various acceleration rates, motion patterns, and imaging applications in comparison with that of the state‐of‐the‐art algorithms of dynamic imaging, including extra‐dimensional golden‐angle radial sparse parallel MRI (XD‐GRASP), low‐rank plus sparse matrix decomposition (L+S), blind compressive sensing (BCS), and 3D convolutional neural networks (3D CNNs).ResultsPNCRNNs increased the peak SNR of 9.07 dB compared with XD‐GRASP, 9.26 dB compared with L+S, 3.48 dB compared with BCS, and 3.14 dB compared with 3D CNN at R = 16. The reconstruction time was 18 ms for each bin, which was two orders faster than that of XD‐GRASP, L+S, and BCS. PNCRNNs provided good reconstruction for various motion patterns, k‐space trajectories, and imaging applications.ConclusionThe proposed PNCRNN provides substantial improvement of the image quality for dynamic golden‐angle radial imaging of the abdomen in comparison with XD‐GRASP, L+S, BCS, and 3D CNN. The reconstruction time of PNCRNN can be as fast as 50 bins per second, due to the use of the highly computational efficient Toeplitz approach.
Accelerated long‐term forgetting is a BACE1 inhibitor‐reversible incipient cognitive phenotype in Alzheimer’s disease model mice
Authors: Ohno Masuo 
Published: March 2021

AbstractAimAfter the continued failure of β‐secretase (BACE1) inhibitor clinical trials in prodromal as well as mild‐to‐moderate Alzheimer's disease (AD), they are shifting to further earlier or asymptomatic stages. The aim of this study is to explore a cognitive paradigm that allows us to more sensitively detect beneficial effects of BACE1 inhibitors in presymptomatic AD.MethodsGRL‐8234 (33.4 mg/kg, ip), a small‐molecule BACE1 inhibitor, was administered once daily for 28 days to the 5XAFD transgenic mouse model of AD. The contextual fear conditioning was used to evaluate the effects of GRL‐8234 on memory deficits in 5XFAD mice at different ages.ResultsChronic administration of GRL‐8234 to 5XFAD mice rescued their contextual memory deficits, when tested 1 day after training at 6‐8 months but not at 12 months of age. Importantly, 4‐month‐old 5XFAD mice retain the ability to form contextual memory equivalent to wild‐type controls, demonstrating that the standard method of 1‐day memory assessment is not suitable for evaluating BACE1 inhibitor efficacy in ameliorating cognitive declines during earlier disease stages. Despite normal contextual memory formation, young 5XFAD mice showed faster forgetting when a longer delay (28 days) intervened between training and memory testing. Notably, GRL‐8234 administered to 4‐month‐old 5XFAD mice during the 28‐day delay reversed accelerated long‐term forgetting almost completely back to wild‐type control levels.ConclusionThe results provide experimental evidence that accelerated long‐term forgetting represents more sensitive memory testing that can help evaluate BACE1 inhibitor therapy in presymptomatic AD populations.
Public administration, context and innovation: A framework of analysis
Authors: Ongaro Edoardo , Gong Ting , Jing Yijia 
Published: March 2021

AbstractInnovation in public administration (PA) has played a pivotal role in building good governance and has attracted significant attention in the academia. The literature on PA innovation is burgeoning; however, this article argues that there is ‘a missing link’ in the extant literature in that the impacts of variation in context on PA innovation have not been sufficiently investigated. This article elaborates the analytical perspectives on the influences of various contexts over PA innovation and the mechanisms through which impacts may take place. Both theoretical and methodological complexities and challenges are apparent in disentangling contextual influences from other factors. The article proposes a research agenda for a context‐orientated comparative analysis of PA innovation and offers a brief illustration regarding contextual differences between China and the European Union in existing studies. The article calls for further studies in this direction.
Advancing drug discovery using the power of the human genome
Authors: Heilbron Karl , Mozaffari Sahar V , Vacic Vladimir , Yue Peng , Wang Wei , Shi Jingchunzi , Jubb Adrian M , Pitts Steven J , Wang Xin 
Published: March 2021

AbstractHuman genetics plays an increasingly important role in drug development and population health. Here we review the history of human genetics in the context of accelerating the discovery of therapies, present examples of how human genetics evidence supports successful drug targets, and discuss how polygenic risk scores could be beneficial in various clinical settings. We highlight the value of direct‐to‐consumer platforms in the era of fast‐paced big data biotechnology, and how diverse genetic and health data can benefit society. © 2021 23andMe, Inc. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Origins and mechanisms leading to aneuploidy in human eggs
Authors: Wartosch Lena , Schindler Karen , Schuh Melina , Gruhn Jennifer R. , Hoffmann Eva R. , McCoy Rajiv C. , Xing Jinchuan 
Published: March 2021

AbstractThe gain or loss of a chromosome—or aneuploidy—acts as one of the major triggers for infertility and pregnancy loss in humans. These chromosomal abnormalities affect more than 40% of eggs in women at both ends of the age spectrum, that is, young girls as well as women of advancing maternal age. Recent studies in human oocytes and embryos using genomics, cytogenetics, and in silico modeling all provide new insight into the rates and potential genetic and cellular factors associated with aneuploidy at varying stages of development. Here, we review recent studies that are shedding light on potential molecular mechanisms of chromosome missegregation in oocytes and embryos across the entire female reproductive life span.
Intranasal glial heterotopia in an infant boy
Authors: Zhang Wei , Tang Lixing , Ge Wentong 
Published: March 2021

ABSTRACTIntroductionNasal glial heterotopia is a rare congenital developmental disorder characterized by meningeal epithelium and/or glial components.Case presentationA 2‐month‐old boy presented for treatment of a congenital mass in the right nasal cavity near the pharynx. The preoperative diagnosis was congenital intranasal neoplasm. Nasal endoscopic resection of the nasopharyngeal mass was performed under general anesthesia. Histological findings in the resected tissue supported a diagnosis of intranasal glial heterotopia. The surgical outcome was good and no surgical site infection occurred. During 1 year of follow‐up, the patient did not exhibit recurrence of heterotopia or related symptoms.ConclusionTransnasal endoscopic surgery is recommended for patients with intranasal glial heterotopia. Thorough preoperative imaging should be performed before glioma resection. The mass should be differentiated from encephalocele to prevent cerebrospinal fluid leakage and meningitis.
Neurodevelopmental outcomes of infants with bronchopulmonary dysplasia
Authors: DeMauro Sara B. 
Published: March 2021

AbstractPreterm infants with bronchopulmonary dysplasia (BPD), and particularly those who develop the most severe forms of chronic lung disease during the neonatal period, are at high risk for poor developmental outcomes throughout childhood. Infants who require mechanical ventilation at 36 weeks post‐menstrual age have significantly increased odds for cerebral palsy, developmental delay at 2 years, and poor academic achievement and low intelligence quotient in adolescence. Over the past several decades, many therapies and care strategies, including steroids, continuous positive airway pressure, surfactant, and other medications have been introduced into clinical practice. These approaches have changed the epidemiology of BPD in very preterm infants. However, BPD remains common and strongly associated with poor development throughout childhood. Only caffeine has been proven to reduce BPD and improve childhood developmental outcomes. In future research, it will be essential to better understand the developmental sequelae of BPD beyond school age and to test interventions to improve developmental trajectories in this population. As new management strategies for BPD are developed, it will be essential to rigorously evaluate both short‐term and long‐term effects before they are introduced into routine neonatal practice.
Catalyst Free Single Step Specific Determination of Hydrazine in UH 25 blend and Determination of Propellant Grade UH 25 blend Using Thiophenes with Active Carbonyl Groups
Authors: Selvakumar S. , Reddy K. Audisesha , Munirathinam B. 
Published: March 2021

AbstractHydrazine and its derivatives such as monomethyl hydrazine (MMH), unsymmetrical dimethyl hydrazine (UDMH), and UH25 (a blend of 75 % UDMH and 25 % hydrazine hydrate by w/w) namely hydrazines are used as fuels (in liquid form) for rocket stages and satellites. They are hypergolic and well‐known toxic compounds. Workplace atmospheres involving vapours / liquid forms of these hydrazines need to be routinely monitored and screened. Simple, economical, and rapid kinetic spectrophotometric techniques are developed to meet the requirements by using thiophene‐3‐carboxaldehyde and 3‐butenone (E)‐1,1,1‐trifluoro‐4‐(3‐thienyl) (CF3enone) and compared. Classical −CHO based technique is applied for UH25 blend (in aqueous medium) in the presence of an acid catalyst. CF3enone based technique is used to determine hydrazine (Hz) in UH25 (in organic medium) selectively at levels as low as 0.05 mM without any catalyst. Variables such as temperature and concentration are optimized to determine UH25 in the concentration range of 0.5 mM to 0.1 M for thiophene‐3‐carboxaldehyde and to determine Hz of UH25 blend in the concentration range of 0.1 mM to 0.6 mM for CF3enone. Minimum detectable limits are found for UH25 and Hz of UH25 blend in the respective studies. GC‐MS study is also carried out to meet the unequivocal identification requirement. Initial rate and fixed time methods are adopted as calibration procedures. Orders of the reactions are found in both studies. Both techniques are simple and rapid after the chemisorption process with derivatizing agents in which pre‐treatment, pre‐concentration, and extraction steps are not involved. Advantages of CF3enone based technique over aldehyde‐based classical technique are 1) requirement of the minimum concentration of derivatizing agent 2) no catalyst 3) selectivity and specificity towards hydrazine in UH25 blend 4) shortened analysis time 5) linear dynamic range at very low concentrations of UH25.
Experimental Investigation and Modeling the Compressive Behavior of NEPE Propellant under Confining Pressure
Authors: Li Hui , Xu Jin‐sheng , Chen Xiong , Hou Yu‐fei , Fan Xing‐gui , Li Meng , Li Hong‐wen 
Published: March 2021

AbstractIn order to study the effects of confining pressure and strain rate on the mechanical properties of the Nitrate Ester Plasticized Polyether (NEPE) propellant, compressive tests were conducted under various confining pressure conditions and strain rates using a new‐designed active gas confining pressure testing machine. The stress‐strain curves and mechanical properties of the NEPE propellant under varying confining pressure conditions and strain rates were obtained. The results show that the compressive mechanical properties of the NEPE propellant are remarkably influenced by the confining pressure and strain rate. The compressive strength under confining pressure is obviously larger than those without applied confining pressure. With the coupled effects of the confining pressure and strain rate, the compressive strength under 5.4 MPa and 6.67×10−2 s−1 is 2.17 times of its value at room condition and 6.67×10−4 s−1. Then, based on previous tensile results, the quantified comparisons of tensile and compressive mechanical properties under different experimental conditions were presented. Finally, a nonlinear constitutive model with damage was constructed to model the effect of pressure. The statistical damage model parameters were defined as ExpDec1 function of pressure P. The calibrated model can accurately predict the mechanical behaviour of the NEPE propellant under different confining pressure conditions and strain rates.
In vitro cytochrome P450‐ and transporter‐mediated drug interaction potential of 6β‐hydroxy‐21‐desacetyl deflazacort—A major human metabolite of deflazacort
Authors: Ma Jiyuan , Beers Brian , Manohar Ravi , Roe Stephen , Colacino Joseph M. , Kong Ronald 
Published: March 2021

Abstract6β‐Hydroxy‐21‐desacetyl deflazacort (6β‐OH‐21‐desDFZ) is a major circulating but not biologically active metabolite of deflazacort (DFZ). In vitro studies were performed to evaluate cytochrome P450 (CYP)‐ and transporter‐mediated drug interaction potentials of 6β‐OH‐21‐desDFZ. Up to 50 µM, the highest soluble concentration in the test system, 6β‐OH‐21‐desDFZ weakly inhibited (IC50 > 50 µM) the enzyme activity of CYPs 1A2, 2B6, 2C8, 2C9, and 2D6, while moderately inhibiting CYP2C19 and CYP3A4 with IC50 values of approximately 50 and 35 μM, respectively. The inhibition was neither time‐dependent nor metabolism‐based. Incubation of up to 50 µM 6β‐OH‐21‐desDFZ with plated cryopreserved human hepatocytes for 48 h resulted in no meaningful concentration‐dependent induction of either mRNA levels or enzyme activity of CYP1A2, CYP2B6, or CYP3A4. In transporter inhibition assays, 6β‐OH‐21‐desDFZ, up to 50 µM, did not show interaction with human OAT1, OAT3, and OCT2 transporters. It weakly inhibited (IC50 > 50 µM) human MATE1, MATE2‐K, and OCT1 transporter activity, and moderately inhibited human MDR1, OATP1B1, and OATP1B3 transporter activity with IC50 values of 19.81 μM, 37.62 μM, and 42.22 μM, respectively. 14C‐6β‐OH‐21‐desDFZ was biosynthesized using bacterial biotransformation and the subsequent study showed that 6β‐OH‐21‐desDFZ was not a substrate for human BCRP, MDR1, MATE1, MATE2‐K, OAT1, OATP1B1, OATP1B3, and OCT2 transporters, but appeared to be an in vitro substrate for the human OAT3 uptake transporter. At plasma concentrations of 6β‐OH‐21‐desDFZ seen in the clinic, CYP‐ and transporter‐mediated drug–drug interactions are not expected following administration of a therapeutic dose of DFZ in Duchenne muscular dystrophy (DMD) patients.