bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of a Novel Inhibitor of Human Purine Nucleoside Phosphorylase by a Simple Hydrophilic Interaction Liquid Chromatography Enzymatic Assay
Authors: Rabuffetti Marco , Rinaldi Francesca , Lo Bianco Alessandra , Speranza Giovanna , Ubiali Daniela , de Moraes Marcela Cristina , Rodrigues Pereira da Silva Luiz Claudio , Massolini Gabriella , Calleri Enrica , Lavecchia Antonio 
Published: January 2021

AbstractHuman purine nucleoside phosphorylase (HsPNP) belongs to the purine salvage pathway of nucleic acids. Genetic deficiency of this enzyme triggers apoptosis of activated T‐cells due to the accumulation of deoxyguanosine triphosphate (dGTP). Therefore, potential chemotherapeutic applications of human PNP inhibitors include the treatment of T‐cell leukemia, autoimmune diseases and transplant tissue rejection. In this report, we present the discovery of novel HsPNP inhibitors by coupling experimental and computational tools. A simple, inexpensive, direct and non‐radioactive enzymatic assay coupled to hydrophilic interaction liquid chromatography and UV detection (LC‐UV using HILIC as elution mode) was developed for screening HsPNP inhibitors. Enzymatic activity was assessed by monitoring the phosphorolysis of inosine (Ino) to hypoxanthine (Hpx) by LC‐UV. A small library of 6‐ and 8‐substituted nucleosides was synthesized and screened. The inhibition potency of the most promising compound, 8‐aminoinosine (4), was quantified through Ki and IC50 determinations. The effect of HsPNP inhibition was also evaluated in vitro through the study of cytotoxicity on human T‐cell leukemia cells (CCRF‐CEM). Docking studies were also carried out for the most potent compound, allowing further insights into the inhibitor interaction at the HsPNP active site. This study provides both new tools and a new lead for developing novel HsPNP inhibitors.
Extraction of nucleic acid in Escherichia coli and Saccharomyces cerevisiae using high electric field pulse application
Authors: Murakami Yuichi , Yamashita Ryo , Sato Takunao , Muramoto Yuji 
Published: January 2021

AbstractAn electroporation that formed the pores on cell membrane after application of high electric field pulses has been used the transformation and the sterilization of cell. In this paper, we reported the extraction method of nucleic acid in Escherichia coli and Saccharomyces cerevisiae using high electric field pulse application. The sample was 1.0 × 10–3 mol/L NaCl aqueous solution contained E. coli and S. cerevisiae. High voltage pulse is applied to the sample at room temperature. These results were shown as the following: (1) When a pulsed electric field of 4 ∼ 13 kV/mm is applied to E. coli and S. cerevisiae, the estimated amount of nucleic acid increases with the increases of strength of applied pulsed electric field. (2) In the case of E. coli, the 2–3 kbp band was confirmed at an electric field of 5 kV/mm or more, and the 10 kbp band was confirmed at an electric field of 8 kV/mm or more. (3) In the case of S. cerevisiae, the 2–3 kbp band was confirmed at an electric field of 9 kV/mm or more. the 10 kbp band could not be confirmed at 13 kV/mm or less.
Synergistic effects of processing parameters on the biochemical and physical properties of tofu made from yellow field pea (Pisum sativum), as determined by response surface methodology
Authors: DePalma Kevin , Smith Brennan , McDonald Armando G. 
Published: January 2021

AbstractPeas are an underutilized crop that do not require allergen labeling and are rarely genetically modified. Peas contain less protein than soy and vary in protein composition. Because peas contain more starch than soy and less lipids, an alternative procedure for pea tofu production needs to be developed to prevent excessive starch gelatinization while promoting curd development. To accomplish this, a response surface model design was utilized to determine optimal oil addition, cook time, and salt concentration. Treatment ranges were from 0.0% to 4.2% for oil addition, 60–134 min for cook time, and 5.0%–9.2% for MgCl2 addition. Treatments had varying effects on tofu texture. Cook time was directly proportional to the hardness and could be used to match the soft, firm, and extra firm texture targets of conventional soy tofu. Protein secondary structure was not related to gel strength, indicating a system with synergies between multiple components other than protein. This research will help satisfy the growing demand for alternatives to soy‐based foods.
Serotonin depletion during the postnatal developmental period causes behavioral and cognitive alterations and decreases BDNF level in the brain of rats
Authors: Saadati Hakimeh , Sadegzadeh Farshid , Sakhaie Nona , Panahpour Hamdollah , Sagha Mohsen 
Published: January 2021

AbstractA survey of the literature indicates that the developmental disruptions in serotonin (5‐HT) levels can influence the brain development and the function. To the best of our knowledge, so far, there are a few studies about the effects of developmental period 5‐HT depletion on cognition and behavior of adult male and female rats. Therefore, in the present study, we examined the effects of postnatal days (PND 10–20) administration of para‐chlorophenylalanine (PCPA, 100 mg/kg, s.c) a 5‐HT synthesis inhibitor, on anxiety‐related behaviors, pain sensitivity, short‐term recognition memory, and hippocampal and prefrontal cortex (PFC) brain‐derived neurotrophic factor (BDNF) mRNA expression in adult male and female rats. Novel object recognition memory (NORM) and behavioral parameters (anxiety‐like behaviors and pain sensitivity) were evaluated in early adulthood and after that, the hippocampi and PFC of the rat's brain were removed for the determination of BDNF mRNA expression. Our results indicated that the postnatal period administration of PCPA impaired short‐term NORM. The postnatal developmental period treatment with PCPA also increased anxiety‐like behaviors in the open field and elevated plus maze (EPM) tests. Postnatal PCPA treatment increased pain sensitivity in the hot plate test in both male and female rats, especially in female animals. In addition, postnatal days serotonin depletion decreased BDNF level in the hippocampus and PFC of both male and female rats. These findings demonstrate that serotonin plays the main role in neurodevelopment, cognitive functions, and behavior. Therefore, serotonergic system dysregulation during the developmental periods may have more adverse influences on the brain development of rats.
Morph‐anatomic and histochemical study of ileum of goose (Alopochen egyptiacus) with special references to immune cells, mucous and serous goblet cells, telocytes, and dark and light smooth muscle fibers
Authors: Anwar Shimaa M. , Abd‐Elhafeez Hanan H. , Abdel‐maksoud Fatma M. , Abdalla Kamal E. H. 
Published: January 2021

AbstractThe morphological characteristics of the ileum of 20 adult male Egyptian geese were determined using LM, SEM, and TEM. The mean length of the ileum in the male goose was approximately 158.71 mm, representing nearly 10.19% of the total length of the small intestine. The ileum is composed of four layers: mucosa, submucosa, muscular layer, and serosa. The mucosal layer comprises the epithelium, lamina propria, and muscularis mucosa. The mucosa forms finger‐like villi and is invaginated at the bases, forming the crypts of Lieberkühn. The ileum is lined by simple columnar epithelium that contains absorptive dark and light enterocytes with two types of goblet cells (mucous and serous varieties) microfold like cells, dendritic reticulum cells, Paneth cells, and a closed type of enteroendocrine cells. The lamina propria has diffuse lymphoid tissue containing lymphocytes, macrophages, mast cells, plasma cells, and heterophils as well as telocytes. The muscularis mucosa comprises circular smooth muscle fibers extending into the core of the villi. The submucosa is a thin layer of elastic‐rich connective tissue. The muscular level consists of four layers, with light and dark smooth muscle fibers. We described in detail the structure of all cellular components and histomorphometric measurements.
High serum ferritin alone as a predictor of mortality and hemophagocytic lymphohistiocytosis
Authors: Kohli Shruti , Chadha Ritu , Rastogi Neha , Yadav Satya Prakash 
Published: January 2021

AbstractWe report here utility of high serum ferritin alone as a predictor of mortality and diagnosis of hemophagocytic lymphohistiocytosis (HLH). We compared mortality in patients with high serum ferritin >5000 ng/mL versus <5000 ng/mL and looked for presence of HLH. Mortality was significantly higher (P‐value .0048) in patients with serum ferritin levels >5000 ug/dL. Of 21 patients with high serum ferritin, a median of three criteria were fulfilled to diagnose HLH. All patients had features of immune‐activation, and 76.2% patients had features of immune‐pathology favoring diagnosis of HLH. Serum ferritin can aid in prediction of mortality and help in the early diagnosis of HLH.
Identification of a novel SUOX pathogenic variants as the cause of isolated sulfite oxidase deficiency in a Chinese pedigree
Authors: Du Peng , Hassan Reem N. , Luo Hualei , Xie Jie , Zhu Yue , Hu Qiuyue , Yan Jin , Jiang Weiying 
Published: January 2021

AbstractBackgroundIsolated sulfite oxidase deficiency (ISOD) is a life‐threatening rare autosomal recessive disorder caused by pathogenic variants in SUOX (OMIM 606887) gene. The aim of our study was to establish a comprehensive genetic diagnosis strategy for the pathogenicity analysis of the SUOX gene within a limited time and to lay the foundation for precise genetic counseling, prenatal diagnosis, and preimplantation genetic diagnosis.MethodsTwo offspring from one set of parents were studied. Next‐generation sequencing (NGS) was used to screen for disease‐causing gene variants in a family with ISOD. Then, Sanger sequencing was performed to verify the presence of candidate variants. Sulfite, homocysteine and uric acid levels were detected in the patients. According to the ACMG/AMP guidelines, the pathogenicity level of novel variants was annotated.ResultsThe nonsense pathogenic variant (c.1200C > G (p.Y400*)) and a duplication (c.1549_1574dup (p.I525 Mfs*102)) were found in the SUOX gene in the proband. The nonsense mutation (c.1200C > G (p.Y400*), pathogenic, isolated sulfite oxidase deficiency, autosomal recessive) has been reported as pathogenic and the duplication (c.1549_1574dup (p.I525 Mfs*102), pathogenic, isolated sulfite oxidase deficiency, autosomal recessive) was novel, which was classified as pathogenic according to the ACMG/AMP Standards and Guidelines.ConclusionWe established the pathogenicity assessment in ISOD patients based on ACMG/AMP Standards and Guidelines and this is the first ISOD patient reported in mainland China. We also discovered that ISOD is caused by SUOX gene duplication mutation, which enriches the spectrum of SUOX pathogenic variants.
Synthesis of brain tumor multicontrast MR images for improved data augmentation
Authors: Kim Sunho , Kim Byungjai , Park HyunWook 
Published: January 2021

PurposeMedical image analysis using deep neural networks has been actively studied. For accurate training of deep neural networks, the learning data should be sufficient and have good quality and generalized characteristics. However, in medical images, it is difficult to acquire sufficient patient data because of the difficulty of patient recruitment, the burden of annotation of lesions by experts, and the invasion of patients’ privacy. In comparison, the medical images of healthy volunteers can be easily acquired. To resolve this data bias problem, the proposed method synthesizes brain tumor images from normal brain images.MethodsOur method can synthesize a huge number of brain tumor multicontrast MR images from numerous healthy brain multicontrast MR images and various concentric circles. Because tumors have complex characteristics, the proposed method simplifies them into concentric circles that are easily controllable. Then, it converts the concentric circles into various realistic tumor masks through deep neural networks. The tumor masks are used to synthesize realistic brain tumor images from normal brain images.ResultsWe performed a qualitative and quantitative analysis to assess the usefulness of augmented data from the proposed method. Data augmentation by the proposed method provided significant improvements to tumor segmentation compared with other GAN‐based methods. Intuitive experimental results are available online at https://github.com/KSH0660/BrainTumor.ConclusionsThe proposed method can control the grade tumor masks by the concentric circles, and synthesize realistic brain tumor multicontrast MR images. In terms of data augmentation, the proposed method can successfully synthesize brain tumor images that can be used to train tumor segmentation networks or other deep neural networks.
Content analysis of identity challenges in patients with haemophilia: A qualitative study
Authors: Dolatkhah Roya , Shabanloei Reza , Ebrahimi Hossein , Ghasempour Mostafa 
Published: January 2021

AbstractAimsInherited bleeding diseases greatly affect education, working, job, social activities and quality of life. We aimed to discover the sources of identity challenges among patients with Haemophilia.DesignThe present study has been designed and performed as a qualitative content analysis research.MethodsParticipants were purposively selected from haemophilia patients referred to our clinic during one year, from March 2018 to April 2019. Data collection was done through semi‐structured, in‐depth interviews using purposeful sampling. Data were analysed based on Granheme and Landman method. The main categories were fear of rejection, losing social roles, discrimination and stigma and marriage breakdown.ResultsPatients with haemophilia encounter several challenges due to physical and social constraints caused by the disease. Such challenges result in disturbances in the self‐identity of the patients.ConclusionAccording to the results of this study, the nurses should plan to have attention to the patients with haemophilia, based on more protection and better supports.
A protocol for cell therapy infusion in neonates
Authors: Baker Elizabeth K. , Wallace Euan M. , Davis Peter G. , Malhotra Atul , Jacobs Susan E. , Hooper Stuart B. , Lim Rebecca 
Published: January 2021

Abstract
Cell therapies for neonatal morbidities are progressing to early phase clinical trials. However, protocols for intravenous (IV) delivery of cell therapies to infants have not been evaluated. It has been assumed the cell dose prescribed is the dose delivered. Early in our clinical trial of human amnion epithelial cells (hAECs), we observed cells settling in the syringe and IV tubing used to deliver the suspension. The effect on dose delivery was unknown. We aimed to quantify this observation and determine an optimal protocol for IV delivery of hAECs to extremely preterm infants. A standard pediatric infusion protocol was modeled in the laboratory. A syringe pump delivered the hAEC suspension over 60 minutes via a pediatric blood transfusion set (200-μm filter and 2.2 mL IV line). The infusion protocol was varied by agitation methods, IV-line volumes (0.2-2.2 mL), albumin concentrations (2% vs 4%), and syringe orientations (horizontal vs vertical) to assess whether these variables influenced the dose delivered. The influence of flow rate (3-15 mL/h) was assessed after other variables were optimized. The standard infusion protocol delivered 17.6% ± 9% of the intended hAEC dose. Increasing albumin concentration to 4%, positioning the syringe and IV line vertically, and decreasing IV-line volume to 0.6 mL delivered 99.7% ± 13% of the intended hAEC dose. Flow rate did not affect dose delivery. Cell therapy infusion protocols must be considered. We describe the refinement of a cell infusion protocol that delivers intended cell doses and could form the basis of future neonatal cell delivery protocols.
Dichloroacetate attenuates the stemness of hepatocellular carcinoma cells via promoting nucleus‐cytoplasm translocation of YAP
Authors: Su Duanyu , Lin Zhian 
Published: January 2021

AbstractThe antitumor effects of dichloroacetate (DCA) have been widely explored, however, its roles in hepatocellular carcinoma (HCC) progression are still unclear. In the current work, we found that DCA had little effects on HCC cell viability, but could attenuate the stemness of HCC cells, which is evident by decreasing the tumor sphere‐formation ability, ALDH activity and the expression of stemness critical regulators. Mechanistic studies based on RNA‐sequencing data showed that DCA activated the Hippo pathway. Furthermore, we indicated that DCA promoted the nucleus‐cytoplasm translocation of YAP, but not TAZ, another critical executor of Hippo pathway. Moreover, suppressing of Hippo pathway using XMU‐MP‐1, an inhibitor of Hippo pathway, partially abrogated DCA‐induced inhibitory effects on HCC cell stemness. This work suggests that DCA might be a potential inhibitor for HCC progression.
Military Operations
Authors: Høiback Harald 
Published: January 2021

AbstractMilitary operations can be a complex and cumbersome undertaking, involving millions of soldiers and tonnes of equipment. Even though war has been part of human experience for time immemorial, systematic thinking about how to prepare, conduct, and use military operations is nonetheless a rather new undertaking. This chapter explores the history of thinking about military operations, broadly defined, and narrows down on operations as the concept is used today.After the historical exploration, the chapter investigates how military operations can be studied. In principle, there are four different ways to approach operations as a field of study. The most common methods are the historical method and operations research, i.e., making heuristic models of reality. Game theory and axiomatic foundationalism are the other two but are far less used than the former two.The development of modern military thinking notwithstanding, it is still difficult to convert military power to strategic gains, and the latter part of the chapter explains why. Military commanders and planning groups do not always get the what and why from the political level, making it difficult to find the how. Military operations are also intrinsically difficult because your opponent will try to make it difficult for you. The concept of an operational level of command is also problematic, since it tends to do the opposite of what is intended. Instead of pulling tactics and strategy closer together, it tends to push them apart. And finally, the word “art” in “operational art” is perhaps also an unfortunate misnomer?
Multiscale structural optimization with concurrent coupling between scales
Authors: Murphy Ryan , Imediegwu Chikwesiri , Hewson Robert , Santer Matthew 
Published: January 2021

AbstractA robust three-dimensional multiscale structural optimization framework with concurrent coupling between scales is presented. Concurrent coupling ensures that only the microscale data required to evaluate the macroscale model during each iteration of optimization is collected and results in considerable computational savings. This represents the principal novelty of this framework and permits a previously intractable number of design variables to be used in the parametrization of the microscale geometry, which in turn enables accessibility to a greater range of extremal point properties during optimization. Additionally, the microscale data collected during optimization is stored in a reusable database, further reducing the computational expense of optimization. Application of this methodology enables structures with precise functionally graded mechanical properties over two scales to be derived, which satisfy one or multiple functional objectives. Two classical compliance minimization problems are solved within this paper and benchmarked against a Solid Isotropic Material with Penalization (SIMP)–based topology optimization. Only a small fraction of the microstructure database is required to derive the optimized multiscale solutions, which demonstrates a significant reduction in the computational expense of optimization in comparison to contemporary sequential frameworks. In addition, both cases demonstrate a significant reduction in the compliance functional in comparison to the equivalent SIMP-based optimizations.
Status of the International Gravity Reference System and Frame
Authors: Wziontek Hartmut , Bonvalot Sylvain , Falk Reinhard , Gabalda Germinal , Mäkinen Jaakko , Pálinkás̆ Vojtech , Rülke Axel , Vitushkin Leonid 
Published: January 2021

AbstractThe increasing importance of terrestrial gravimetry in monitoring global change processes, in providing a reference for satellite measurements and in applications in metrology necessitates a stable reference system reflecting the measurement accuracy achievable by modern gravimeters. Therefore, over the last decade, the International Association of Geodesy (IAG) has developed a system to achieve accurate, homogeneous, long-term global recording of Earth’s gravity, while taking advantage of the potential of today’s absolute gravity measurements. The current status of the International Gravity Reference System and Frame is presented as worked out by the IAG Joint Working Group 2.1.1 “Establishment of a global absolute gravity reference system” during the period 2015–2019. Here, the system is defined by the instantaneous acceleration of free-fall, expressed in the International System of Units (SI) and a set of conventional corrections for the time-independent components of gravity effects. The frame as the systems realization includes a set of conventional temporal gravity corrections which represent a uniform set of minimum requirements. Measurements with absolute gravimeters, the traceability of which is ensured by comparisons and monitoring at reference stations, provide the basis of the frame. A global set of such stations providing absolute gravity values at the microgal level is the backbone of the frame. Core stations with at least one available space geodetic technique will provide a link to the terrestrial reference frame. Expanded facilities enabling instrumental verification as well as repeated regional and additional comparisons will complement key comparisons at the level of the International Committee for Weights and Measures (CIPM) and ensure a common reference and the traceability to the SI. To make the gravity reference system accessible to any user and to replace the previous IGSN71 network, an infrastructure based on absolute gravity observations needs to be built up. This requires the support of national agencies, which are encouraged to establish compatible first order gravity networks and to provide information about existing absolute gravity observations.