bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of Grapiprant and Its Stability Testing under Changing Environmental Conditions
Authors: Gumułka Paweł , Tarsa Monika , Dąbrowska Monika , Starek Małgorzata
Published: November 2022

Grapiprant is a new analgesic and anti-inflammatory drug belonging to the piprant class, approved in 2016 by the FDA Veterinary Medicine Center for the treatment of pain and inflammation associated with osteoarthritis in dogs. It acts as a highly selective antagonist of the EP4 receptor, one of the four prostaglandin E2 (PGE2) receptor subtypes. It has been shown to have anti-inflammatory effects in rat models of acute and chronic inflammation and clinical studies in people with osteoarthritis. The current state of knowledge suggests the possibility of using it in oncological therapy. The manuscript presents the development of conditions for the identification and quantitative determination of grapiprant by thin-layer chromatography with densitometric detection. The optimal separation of the substance occurs using silica gel 60F254 chromatographic plates and the mobile phase containing ethyl acetate-toluene-butylamine. Validation (according to ICH requirements) showed that the developed method is characterized by straightness of results in a wide concentration range with the limit of detection of 146.65 µg/mL. The %RSD values of the precision and accuracy confirm the sensitivity and reliability of the developed procedure. Next, the method was used for quantification of grapiprant in a pharmaceutical preparation, and for stability studies under various environmental conditions. Additionally, the mass studies were carried out on the stressed samples using the UPLC-MS/MS method. The degradation products were primarily characterized by comparing their mass fragmentation profiles with those of the drug. The results indicated a potential degradation pathway for grapiprant.
Adenosine Receptors Profile in Fibromuscular Dysplasia
Authors: Guiol Claire , El Harake Sarah , Fromonot Julien , Chefrour Mohamed , Gastaldi Marguerite , Alibouch Yassine , Doublier Maxime , Deharo Pierre , Sarlon Gabrielle , Marlinge Marion , Lalevee Nathalie , Guieu Régis , Silhol François
Published: November 2022

Fibromuscular dysplasia (FMD) is a non-inflammatory vascular disease that is characterized by unexplained systemic hypertension occurring in young people, associated with arterial stenosis, aneurysm rupture, intracranial/renal infarction, and stroke. Although the gold standard for the diagnosis remains catheter-angiography, biological markers would be helpful due to the delay from first symptom to diagnosis. Adenosine is an ATP derivative, that may be implicated in FMD pathophysiology. We hypothesized that changes in adenosine blood level (ABL) and production of adenosine receptors may be associated with FMD. Using peripheral blood mononuclear cells, we evaluated A1, A2A, and A2B receptor production by Western blot, in 67 patients (17 men and 50 women, mean (range) age 55 (29–77) years and 40 controls, 10 men and 30 women, mean (range) age 56 (37–70)). ABL was evaluated by liquid chromatography, mass spectrometry. ABL was significantly higher in patients vs. controls, mean (range): 1.7 (0.7–3) µmol/L vs. controls 0.6 (0.4–0.8) µmol/L (+180%) p < 0.001. While A1R and A2AR production did not differ in patients and controls, we found an over-production of A2BR in patients: 1.70 (0.90–2.40; arbitrary units) vs. controls = 1.03 (0.70–1.40), mean + 65% (p < 0.001). A2BR production with a cut off of 1.3 arbitrary units, gives a good sensitivity and specificity for the diagnosis. Production measurement of A2BR on monocytes and ABL could help in the diagnosis, especially in atypical or with poor symptoms.
Effective Microorganisms and Glass Nanopowders from Waste Bottle Inclusion on Early Strength and Microstructure Properties of High-Volume Fly-Ash-Based Concrete
Authors: Onaizi Ali M. , Huseien Ghasan Fahim , Shukor Lim Nor Hasanah A. , Tang W. C. , Alhassan Mohammad , Samadi Mostafa
Published: November 2022

In concrete production, the use of high-volume fly ash (FA) as the cement substitute became interesting to achieve more sustainable and eco-friendly construction materials. However, concrete produced using high volumes of FA as cement substitute suffers from various limitations such as low strength at early ages. Considering the engineering solutions and economy of FA-included concrete, it has become vital to address such issues. In this perception, some concrete mixes were designed using more abundant and low-cost local waste materials such as waste glass bottle nanopowders (WGBNPs) and effective microorganisms (EMs) to determine the feasibility of compensating for the strength loss at early ages due to FA inclusion. The proposed mixes contained 10% of EMs as water replacement, 50% of FA, and various percentages of WGBNPs as cement replacement. The effects of EMs and WGBNPs inclusion on the early strength and microstructure properties of the produced FA-based concrete mixes were determined. The results show that the strength indexes of the concrete at all test ages were improved due to WGBNP and EM incorporation. At almost all curing ages, the mechanical performance of the concrete made with 10% EMs and 4% WGBNPs was comparable to that of normal concrete (control mix), wherein the mix containing 6% WGBNPs outperformed the control mix. The microstructure analysis of the studied mixes revealed an increase in the hydration products, structural compactness, and homogeneity due to the synergy of WGBNPs and EMs, especially the specimen made using 10% EMs and 6% WGBNPs. It is established that the proper utilization of EMs and WGBNPs in FA-based concrete can be beneficial for waste recycling and landfill problems, thus lowering environment pollution.
Molecularly Designed Ion-Imprinted Nanoparticles for Real-Time Sensing of Cu(II) Ions Using Quartz Crystal Microbalance
Authors: Aydoğan Nihan , Aylaz Gülgün , Bakhshpour Monireh , Tugsuz Tugba , Andaç Müge
Published: November 2022

A molecularly designed imprinting method was combined with a gravimetric nanosensor for the real-time detection Cu(II) ions in aqueous solutions without using expensive laboratory devices. Thus, 1:1 and 2:1 mol-ratio-dependent coordination modes between Cu(II), N-methacyloly-L histidine methyl ester (MAH) functional monomer complexes, and their four-fold and six-fold coordinations were calculated by means of density functional theory molecular modeling. Cu(II)-MIP1 and Cu(II)-MIP2 nanoparticles were synthesized in the size range of 80–100 nm and characterized by SEM, AFM and FTIR. Cu(II)-MIP nanoparticles were then conducted to a quartz crystal microbalance sensor for the real-time detection of Cu(II) ions in aqueous solutions. The effects of initial Cu(II) concentration, selectivity, and imprinting efficiency were investigated for the optimization of the nanosensor. Linearity of 99% was obtained in the Cu(II) ion linear concentration range of 0.15–1.57 µM with high sensitivity. The LOD was obtained as 40.7 nM for Cu(II)-MIP2 nanoparticles. The selectivity and the imprinting efficiency of the QCM nanosensor were obtained significantly in the presence of competitive ion samples (Co(II), Ni(II), Zn(II), and Fe(II)). The results are promising for sensing Cu(II) ions as environmental toxicants in water by combining molecularly designed ion-imprinted nanoparticles and a gravimetric sensor.
Synthesis and Characterization of TiO2 Thick Films for Glucose Sensing
Authors: Silva-Galindo G. , Zapata-Torres M.
Published: November 2022

In this paper, we present the results of a non-enzymatic electrochemical glucose biosensor based on TiO2. An anatase working electrode was synthesized using the spin coating technique with the polymeric precursor method and dispersed TiO2 nanoparticles. Through scanning electron microscopy, it was observed that the electrode presented an irregular surface with clusters of nanoparticles. Electrochemical characterization indicated that the response was directly related to the morphology of the electrode. In the presence of glucose, the electrode exhibited adsorption behavior toward the molecules, enabling their recognition. The electrode was tested by employing PBS (phosphate buffer solutions) with varying pH values (from 4 to 9), demonstrating its electrochemical stability, even in the presence of glucose. Amperometric characterization was used to determine that the working region appeared from 0.2 mM to 2 mM, with a sensitivity of 4.46 μAcm−2mM−1 in PBS pH 7. The obtained results suggest that TiO2-based electrodes could be used for the detection of glucose concentration in sweat (0.277–1 mM) and saliva (0.23–1.77 mM).
Hand and Foot Selection in Mental Body Rotations Involves Motor-Cognitive Interactions
Authors: Dahm Stephan Frederic , Muraki Emiko J. , Pexman Penny M.
Published: November 2022

Action imagery involves the mental representation of an action without overt execution, and can contribute to perspective taking, such as that required for left-right judgments in mental body rotation tasks. It has been shown that perspective (back view, front view), rotational angle (head-up, head-down), and abstractness (abstract, realistic) of the stimulus material influences speed and correctness of the judgement. The present studies investigated whether left-right judgements are more difficult on legs than on arms and whether the type of limb interacts with the other factors. Furthermore, a combined score for speed and accuracy was explored to eliminate possible tradeoffs and to obtain the best possible measure of subjects’ individual ability. Study 1 revealed that the front view is more difficult than the back view because it involves a vertical rotation in perspective taking. Head-down rotations are more difficult than head-up rotations because they involve a horizontal rotation in perspective taking. Furthermore, leg stimuli are more difficult than hand stimuli, particularly in head-down rotations. In Study 2, these findings were replicated in abstract stimuli as well as in realistic stimuli. In addition, perspective taking for realistic stimuli in the back view is easier than realistic stimuli in the front view or abstract stimuli (in both perspectives). We conclude that realistic stimulus material facilitates task comprehension and amplifies the effects of perspective. By replicating previous findings, the linear speed-accuracy score was shown to be a valid measure to capture performance in mental body rotations.
Development of a C6 Glioma Cell Model System to Assess Effects of Cathodic Passively Balanced Electrical Stimulation on Responses to Neurotransmitters: Implications for Modulation of Intracellular Nitric Oxide, Chloride, and Calcium Ions
Authors: Platt David C. , Apuzzo C. Fiore , Jones Marjorie A. , Cedeno David L. , Vallejo Ricardo
Published: November 2022

This research focused on the development of an astrocyte cell model system (C6 glioma) for the assessment of molecular changes in response to cathodic passively balanced pulsed electrical stimulation at a rate of 50 Hz (60 µs duration, 0.15 mA intensity). Cells treated with selected neurotransmitters (glutamate, adenosine, D-serine, and γ-aminobutyric acid) were monitored (using specific fluorescent probes) for changes in levels of intracellular nitric oxide, calcium ions, and/or chloride. ES exerted an inhibitory effect on NO, increased calcium and had no effect on chloride. Using this model, cells can be assessed qualitatively and quantitatively for changes and these changes can be correlated with the putative molecular effects that electrical stimulation has on astrocytes and their role in glia-mediated diseases. This model system allows for faster and cheaper experiments than those involving animal models due to the potential to easily vary the conditions, reduce the number of variables (especially problematic in animal models), and closely monitor the cellular effects.
Elevated Level of Cerebrospinal Fluid Pyruvate Dehydrogenase Kinase 4 Is a Predictive Biomarker of Clinical Outcome after Subarachnoid Hemorrhage
Authors: Gao Xuan , Zhang Huasheng , Peng Zheng , Zhuang Zong , Li Wei
Published: November 2022

Subarachnoid hemorrhage (SAH) is a central nervous system disease with high mortality and morbidity. Some independent factors valuable for prognosis prediction in patients with SAH are still lacking. In our earlier study, we found that PDK4 exerts a protective effect after SAH, primarily by reducing oxidative stress and neuronal death via the ROS/ASK1/p38 signaling pathway. Therefore, we investigated the changes in the level of pyruvate dehydrogenase kinase 4 (PDK4) in patients after subarachnoid hemorrhage (SAH) and analyzed the value of the cerebrospinal fluid (CSF) PDK4 level in predicting the prognoses of patients with SAH after interventional embolization surgery. Some knee arthritis subjects who needed surgery were recruited as a control group. The results showed that PDK4 expression was elevated in the CSF of SAH patients compared with that of controls. PDK4 levels in CSF (OR = 4.525; 95% CI: 1.135–18.038; p = 0.032), time to surgery (OR = 0.795; 95% CI: 0.646–0.977; p = 0.029), and initial GCS scores (OR = 2.758; 95% CI: 0.177–43.106; p = 0.469) were independent prognostic risk factors for SAH patients after surgery. The receiver operating characteristic (ROC) curve showed PDK4 levels in CSF had a higher predictive value. Thus, PDK4 in CSF could be an independent prognostic risk factor for SAH patients after surgery. PDK4 has the potential to serve as a new therapeutic target and biomarker for use in the diagnosis of SAH severity and the prediction of recovery.
Recycling of Waste Stone Powder in High Fluidity Grouting Materials for Geotechnical Engineering Reinforcement
Authors: Liu Xingquan , Rong Yangyang , Chen Xinming , Chen Xi , Zhang Wenxiang
Published: November 2022

Clay cement grout is frequently employed in geotechnical reinforcement projects. However, laboratory test revealed that clay cement slurry does not consolidate in a closed environment for an extended period of time, with cracks forming during the consolidation process under natural conditions, indicating that the geotechnical reinforcement poses dangers. Stone powder is a powdery solid waste similar to clay materials. Stone powder particle surfaces provide an attachment point for cement reaction, which can speed up cement hydration, with the ability to substitute clay cement slurry. According to our findings, the bleeding rate of clay cement slurry is 14.80% at 290 mm fluidity, and that of the same mass ratio (1:3) as stone powder cement slurry is 11.09%. The bleeding rate is minimal, which promotes the creation of an integral structure after setting between the slurry and lose rock and soil. Mechanical test results show that the strength of the stone powder cement slurry hardened body is 1458 kPa, whereas the strength of the clay cement slurry hardened body is 436 kPa. Microstructural analysis shows that the stone powder cement hardened body has more hydration products and is porous than the clay cement hardened body. The hardened body of stone powder cement slurry has high strength and resistance to external loads, which can increase the bearing capacity and improve the geotechnical reinforcement effect.
Fatigue Damage Mitigation for Welded Beam-to-Column Connections in Steel High-Rise Buildings Using Passive Vibration Control
Authors: Fang Zhao , Zhang Jianshao , Yang Fan , Li Aiqun
Published: November 2022

To investigate the use of vibration control systems in fatigue damage mitigation for welded beam-to-column connections in steel high-rise buildings, cases of both a single connection under constant amplitude cyclic loading and multi-connections in a high-rise building under the stochastic wind, with and without the fluid viscous damper (VFD) and the tuned mass damper (TMD), are discussed respectively. The finite element analysis and the fatigue assessment are conducted so that the mitigation effect, the effect of technical parameters and the conditions of both high-cycle fatigue and low-cycle fatigue are all discussed. The results show that the VFD and the TMD systems are both effective in the mitigation of local fatigue damage along with the structural displacement for both cases. The VFD generally has a better mitigation effect than the TMD and it starts to take effect instantly with the external loading, but it causes a phase difference in structural responses, while the situation of the TMD is quite the opposite. The displacement and the local stress show similar and synchronous mitigation trends so that the damping systems can be designed based on either of them. The VFD should be designed with a smaller damping exponent and a larger damping coefficient in a braced installation form, while the TMD can be designed using the optimal parameters. The optimized VFD layout plan is that VFDs are placed between the two connections with large relative displacement and relative velocity on higher floors and these two connections with VFDs should be near to the targeted connection. The negative fatigue damage mitigation mainly stems from insufficient lateral support force so that the direct installation of VFDs may result in a negative fatigue damage mitigation effect in the connections with limited lateral support.
Improving the Performance of Piled Raft Foundations Using Deformation Adjustors: A Case Study
Authors: Zhu Rui , Zhou Feng , Wan Zhihui , Deng Shengjun , Dong Xin , Zhou Zekun , Xing Wei
Published: November 2022

Complicated soil conditions are direct difficulties for high-rise building projects. A new device called a deformation adjustor, which is used to optimize the stiffness distribution in the piled raft system, has achieved good results for this challenge. This paper presents a case study on the application of deformation adjustors to improve the performance of a piled raft foundation. This case study describes the preliminary design of pile-raft foundations with deformation adjustors, followed by numerical analysis. Based on the numerical study, the potential savings are demonstrated due to the good performance of soil bearing capacity. Comparing the numerical results with the monitoring results in raft settlements, earth pressures, deformation amount of deformation adjustors, pile top reactions, and load-sharing ratios between soils and piles, the accuracy of the design schemes with an aided numerical analysis is verified. Through a long-term monitoring, soils below the raft carried 63% of the total applied loads, while the piles bear 37% of the loads. This case study proved that a piled raft foundation with deformation adjustors was an effective and economical design scheme, which can make full use of the soil bearing capacity. It is of great significance to facilitate the design and construction of piled raft foundations in complicated soil conditions.
Nanoparticle Enhancement of Natural Killer (NK) Cell-Based Immunotherapy
Authors: Murugan Dhanashree , Murugesan Vasanth , Panchapakesan Balaji , Rangasamy Loganathan
Published: November 2022

Natural killer (NK) cells are one of the first lines of defense against infections and malignancies. NK cell-based immunotherapies are emerging as an alternative to T cell-based immunotherapies. Preclinical and clinical studies of NK cell-based immunotherapies have given promising results in the past few decades for hematologic malignancies. Despite these achievements, NK cell-based immunotherapies have limitations, such as limited performance/low therapeutic efficiency in solid tumors, the short lifespan of NK cells, limited specificity of adoptive transfer and genetic modification, NK cell rejection by the patient’s immune system, insignificant infiltration of NK cells into the tumor microenvironment (TME), and the expensive nature of the treatment. Nanotechnology could potentially assist with the activation, proliferation, near-real time imaging, and enhancement of NK cell cytotoxic activity by guiding their function, analyzing their performance in near-real time, and improving immunotherapeutic efficiency. This paper reviews the role of NK cells, their mechanism of action in killing tumor cells, and the receptors which could serve as potential targets for signaling. Specifically, we have reviewed five different areas of nanotechnology that could enhance immunotherapy efficiency: nanoparticle-assisted immunomodulation to enhance NK cell activity, nanoparticles enhancing homing of NK cells, nanoparticle delivery of RNAi to enhance NK cell activity, genetic modulation of NK cells based on nanoparticles, and nanoparticle activation of NKG2D, which is the master regulator of all NK cell responses.
Protein Arginine Methyltransferases as Therapeutic Targets in Hematological Malignancies
Authors: Sauter Camille , Simonet John , Guidez Fabien , Dumétier Baptiste , Pernon Baptiste , Callanan Mary , Bastie Jean-Noël , Aucagne Romain , Delva Laurent
Published: November 2022

Arginine methylation is a common post-translational modification affecting protein activity and the transcription of target genes when methylation occurs on histone tails. There are nine protein arginine methyltransferases (PRMTs) in mammals, divided into subgroups depending on the methylation they form on a molecule of arginine. During the formation and maturation of the different types of blood cells, PRMTs play a central role by controlling cell differentiation at the transcriptional level. PRMT enzymatic activity is necessary for many cellular processes in hematological malignancies, such as the activation of cell cycle and proliferation, inhibition of apoptosis, DNA repair processes, RNA splicing, and transcription by methylating histone tails’ arginine. Chemical tools have been developed to inhibit the activity of PRMTs and have been tested in several models of hematological malignancies, including primary samples from patients, xenografts into immunodeficient mice, mouse models, and human cell lines. They show a significant effect by reducing cell viability and increasing the overall survival of mice. PRMT5 inhibitors have a strong therapeutic potential, as phase I clinical trials in hematological malignancies that use these molecules show promising results, thus, underlining PRMT inhibitors as useful therapeutic tools for cancer treatment in the future.
Intravascular NK/T-Cell Lymphoma: What We Know about This Diagnostically Challenging, Aggressive Disease
Authors: Zanelli Magda , Parente Paola , Sanguedolce Francesca , Zizzo Maurizio , Palicelli Andrea , Bisagni Alessandra , Carosi Illuminato , Trombetta Domenico , Mastracci Luca , Ricci Linda , Pancetti Saverio , Martino Giovanni , Broggi Giuseppe , Caltabiano Rosario , Cavazza Alberto , Ascani Stefano
Published: November 2022

Intravascular lymphoma is a form of lymphoid malignancy characterized by neoplastic cells growing almost exclusively within the lumina of small- to medium-sized blood vessels. Most cases are of B-cell origin with rare cases of natural killer or T-cell lineage. Extranodal sites are affected, mainly the skin and central nervous system, although any organ may be involved. Intravascular NK/T-cell lymphoma deserves special attention because of its clinicopathologic features and the need for adequate immunophenotyping combined with clonality test for a proper diagnosis. Moreover, intravascular NK/T-cell lymphoma is strongly linked to Epstein–Barr virus (EBV), which is considered to play a role in tumorigenesis and to be responsible for the aggressive behavior of the disease. In this paper, we review the current knowledge on this rare lymphoma and, in particular, the most recent advances about its molecular landscape. The main distinguishing features with other EBV-related entities, such as extranodal NK/T-cell lymphoma, EBV-positive primary nodal T/NK-cell lymphoma, and aggressive NK-cell leukemia, are discussed to help pathologists obtain the correct diagnosis and consequently develop an adequate and prompt therapy response.
N-Iodosuccinimide as a Precatalyst for C–N Bond-Forming Reactions from Alcohols under Mild Reaction Conditions
Authors: Ajvazi Njomza , Stavber Stojan
Published: November 2022

We report an efficient and selective methodology for the direct cross-coupling of alcohols with N-nucleophiles mediated by N-iodosuccinimide (NIS) as the non-metal, commercially available, low-cost, and most effective precatalyst among the N-halosuccinimides (NXSs) under mild reaction conditions enhancing the green chemical profiles of these reactions. The scale-up procedure was accomplished with almost quantitative yield, verifying the presented method’s synthetic applicability and potential for industrial application.
Perspective on CO2 Hydrogenation for Dimethyl Ether Economy
Authors: Liu Chang , Liu Zhongwen
Published: November 2022

The CO2 hydrogenation to dimethyl ether (DME) is a potentially promising process for efficiently utilizing CO2 as a renewable and cheap carbon resource. Currently, the one-step heterogeneous catalytic conversion of CO2 to value-added chemicals exhibits higher efficiency than photocatalytic or electrocatalytic routes. However, typical catalysts for the one-step CO2 hydrogenation to DME still suffer from the deficient space–time yield and stability in industrial demonstrations/applications. In this perspective, the recent development of the one-step CO2 hydrogenation to DME is focused on different catalytic systems by examining the reported experimental results and the reaction mechanism including the catalytic nature of active sites, activation modes and of CO2 molecules under relevant conditions; surface intermediates are comparatively analyzed and discussed. In addition to the more traditional Cu-based, Pd-based, and oxide-derived bifunctional catalysts, a further emphasis is given to the characteristics of the recently emerged In2O3-based bifunctional catalysts for the one-step conversion of CO2 to DME. Moreover, GaN itself, as a bifunctional catalyst, shows over 90% DME selectivity and a reasonably high activity for one-step CO2 hydrogenation, and the direct hydrogenation of CO2 via the unique non-methanol intermediate mechanism is highlighted as an important illustration for exploring new catalytic systems. With these analyses and current understandings, the research directions in the aspects of catalysis and DME economy are suggested for the further development of one-step DME synthesis from CO2 hydrogenation.
Src Family Kinases Facilitate the Crosstalk between CGRP and Cytokines in Sensitizing Trigeminal Ganglion via Transmitting CGRP Receptor/PKA Pathway
Authors: Nie Lingdi , Sun Kai , Gong Ziyang , Li Haoyang , Quinn John P. , Wang Minyan
Published: November 2022

The communication between calcitonin gene-related peptide (CGRP) and cytokines plays a prominent role in maintaining trigeminal ganglion (TG) and trigeminovascular sensitization. However, the underlying regulatory mechanism is elusive. In this study, we explored the hypothesis that Src family kinases (SFKs) activity facilitates the crosstalk between CGRP and cytokines in sensitizing TG. Mouse TG tissue culture was performed to study CGRP release by enzyme-linked immunosorbent assay, cytokine release by multiplex assay, cytokine gene expression by quantitative polymerase chain reaction, and phosphorylated SFKs level by western blot. The results demonstrated that a SFKs activator, pYEEI (YGRKKRRQRRREPQY(PO3H2)EEIPIYL) alone, did not alter CGRP release or the inflammatory cytokine interleukin-1β (IL-1β) gene expression in the mouse TG. In contrast, a SFKs inhibitor, saracatinib, restored CGRP release, the inflammatory cytokines IL-1β, C-X-C motif ligand 1, C-C motif ligand 2 (CCL2) release, and IL-1β, CCL2 gene expression when the mouse TG was pre-sensitized with hydrogen peroxide and CGRP respectively. Consistently with this, the phosphorylated SFKs level was increased by both hydrogen peroxide and CGRP in the mouse TG, which was reduced by a CGRP receptor inhibitor BIBN4096 and a protein kinase A (PKA) inhibitor PKI (14–22) Amide. The present study demonstrates that SFKs activity plays a pivotal role in facilitating the crosstalk between CGRP and cytokines by transmitting CGRP receptor/PKA signaling to potentiate TG sensitization and ultimately trigeminovascular sensitization.
Integration of O-GlcNAc into Stress Response Pathways
Authors: Fahie Kamau M. M. , Papanicolaou Kyriakos N. , Zachara Natasha E.
Published: November 2022

The modification of nuclear, mitochondrial, and cytosolic proteins by O-linked βN-acetylglucosamine (O-GlcNAc) has emerged as a dynamic and essential post-translational modification of mammalian proteins. O-GlcNAc is cycled on and off over 5000 proteins in response to diverse stimuli impacting protein function and, in turn, epigenetics and transcription, translation and proteostasis, metabolism, cell structure, and signal transduction. Environmental and physiological injury lead to complex changes in O-GlcNAcylation that impact cell and tissue survival in models of heat shock, osmotic stress, oxidative stress, and hypoxia/reoxygenation injury, as well as ischemic reperfusion injury. Numerous mechanisms that appear to underpin O-GlcNAc-mediated survival include changes in chaperone levels, impacts on the unfolded protein response and integrated stress response, improvements in mitochondrial function, and reduced protein aggregation. Here, we discuss the points at which O-GlcNAc is integrated into the cellular stress response, focusing on the roles it plays in the cardiovascular system and in neurodegeneration.
A Balance between Transmembrane-Mediated ER/Golgi Retention and Forward Trafficking Signals in Glycophorin-Anion Exchanger-1 Interaction
Authors: Hsu Kate , Lee Ting-Ying , Lin Jian-Yi , Chen Pin-Lung
Published: November 2022

Anion exchanger-1 (AE1) is the main erythroid Cl−/HCO3− transporter that supports CO2 transport. Glycophorin A (GPA), a component of the AE1 complexes, facilitates AE1 expression and anion transport, but Glycophorin B (GPB) does not. Here, we dissected the structural components of GPA/GPB involved in glycophorin-AE1 trafficking by comparing them with three GPB variants—GPBhead (lacking the transmembrane domain [TMD]), GPBtail (mainly the TMD), and GP.Mur (glycophorin B-A-B hybrid). GPB-derived GP.Mur bears an O-glycopeptide that encompasses the R18 epitope, which is present in GPA but not GPB. By flow cytometry, AE1 expression in the control erythrocytes increased with the GPA-R18 expression; GYP.Mur+/+ erythrocytes bearing both GP.Mur and GPA expressed more R18 epitopes and more AE1 proteins. In contrast, heterologously expressed GPBtail and GPB were predominantly localized in the Golgi apparatus of HEK-293 cells, whereas GBhead was diffuse throughout the cytosol, suggesting that glycophorin transmembrane encoded an ER/Golgi retention signal. AE1 coexpression could reduce the ER/Golgi retention of GPB, but not of GPBtail or GPBhead. Thus, there are forward-trafficking and transmembrane-driven ER/Golgi retention signals encoded in the glycophorin sequences. How the balance between these opposite trafficking signals could affect glycophorin sorting into AE1 complexes and influence erythroid anion transport remains to be explored.
Bioinformatics Analysis and Validation of the Role of Lnc-RAB11B-AS1 in the Development and Prognosis of Hepatocellular Carcinoma
Authors: Wang Dedong , Hu Xiangzhi , Chen Jinbin , Liang Boheng , Zhang Lin , Qin Pengzhe , Wu Di
Published: November 2022

Lnc-RAB11B-AS1 is reported to be dysregulated in several types of cancers and can function as both an oncogene and tumor suppressor gene. To evaluate the potential role of lnc-RAB11B-AS1 in hepatocellular carcinoma (HCC), we investigated and evaluated its expression in HCC based on the data mining of a series of public databases, including TCGA, GEO, ICGC, HPA, DAVID, cBioPortal, GeneMIANA, TIMER, and ENCORI. The data showed downregulation of lnc-RAB11B-AS1 in HCC and was accompanied by the synchronous downregulation of the targeted RAB11B mRNA and its protein. Low expression of lnc-RAB11B-AS1 was associated with shorter overall survival (OS) and disease-free survival (DFS) of HCC patients, PD1/PD-L1 was correlated with low expression of RAB11B. Furthermore, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed a correlation between immune cell change and non-alcoholic fatty liver disease. The above findings revealed that lnc-RAB11B-AS1 was down-regulated in HCC and closely associated with the clinical stage of the HCC patients, suggesting that lnc-RAB11B-AS1 could be a possible predictor for HCC and a potential new therapeutic target for the treatment of HCC.
Prevalence and Related Risk Factors of Vitamin D Deficiency in Saudi Children with Epilepsy
Authors: Al Khalifah Reem , Hamad Muddathir H. , Hudairi Abrar , Al-Sulimani Lujain K. , Al Homyani Doua , Al Saqabi Dimah , Bashiri Fahad A.
Published: November 2022

Background: Vitamin D has a role in the pathogenesis of many medical disorders, especially those of the central nervous system. It is essential in maintaining the bone health of children. However, patients with epilepsy are at high risk of developing vitamin D deficiency due to antiseizure medications (ASMs). Therefore, we aimed to assess the prevalence of vitamin D deficiency and related risk factors in children with epilepsy. Methods: This is the baseline report of a pragmatic, randomized, controlled, open-label trial that assessed the impact of vitamin D supplementation in preventing vitamin D deficiency (NCT03536845). We included children with epilepsy aged 2–16 years who were treated with ASMs from December 2017 to March 2021. Children with preexisting vitamin D metabolism problems, vitamin-D-dependent rickets, malabsorption syndromes, renal disease, and hepatic disease were excluded. The baseline demographic data, anthropometric measurements, seizure types, epilepsy syndromes, ASMs, and seizure control measures were recorded. Blood tests for vitamin D (25-hydroxyvitamin D [25(OH)D), serum calcium, serum phosphorus, and parathyroid hormone levels were performed. Based on vitamin D concentration, patients were categorized as deficient (<50 nmol/L), insufficient (74.9–50 nmol/L), or normal (>75 nmol/L). Results: Of 159 recruited children, 108 (67.92%) had generalized seizures, 44 (27.67%) had focal seizures, and 7 (4.4%) had unknown onset seizures. The number of children receiving monotherapy was 128 (79.0%) and 31 (19.1%) children were receiving polytherapy. The mean vitamin D concentration was 60.24 ± 32.36 nmol/L; 72 patients (45.28%) had vitamin D deficiency and 45 (28.3%) had vitamin D insufficiency. No significant difference in vitamin D concentration was observed between children receiving monotherapy and those receiving polytherapy. The main risk factors of vitamin D deficiency were obesity and receiving enzyme-inducer ASMs. Conclusions: The prevalence of vitamin D deficiency was high among children with epilepsy. Obese children with epilepsy and those on enzyme-inducer ASMs were at increased risk for vitamin D deficiency. Further studies are needed to establish strategies to prevent vitamin D deficiency.
Successful Treatment of Pediatric Acute Myeloid Leukemia Presenting with Hyperbilirubinemia Secondary to Myeloid Sarcoma: A Case Report
Authors: Shash Hwazen A. , Khairy Ashraf M.
Published: November 2022

Myeloid sarcoma (MS), a tumor consisting of myeloid blasts with or without maturation, occurs at anatomical sites other than the bone marrow. MS of the gastrointestinal tract presenting with jaundice in children is rare. We report the case of a 4-year-old boy with a 6-week history of symptoms of obstructive jaundice due to a peripancreatic mass compressing the common bile duct. Six weeks later, blasts were found in a peripheral smear prior to surgical biopsy; bone marrow evaluation and flow cytometry results led to a diagnosis of acute myeloid leukemia (AML) with MS. No further invasive testing or temporary drainage was performed. He was started on induction therapy with full therapeutic doses of cytarabine, dose reductions of etoposide, and escalating doses of daunorubicin. His liver enzymes normalized, and he completed subsequent cycles of chemotherapy with full doses. The abdominal ultrasound showed resolution of the mass after the second cycle of chemotherapy. He is currently in remission three years after completing therapy. AML-directed chemotherapy in patients with obstructive jaundice secondary to MS may be beneficial without requiring invasive testing or temporary drainage procedures. Daily follow-up is crucial for chemotherapy dose modifications. Management plans should be individualized according to the patient’s clinical condition.
Personalizing Child Protection: The Clinical Value and Usability of a Needs Assessment Instrument in The Netherlands
Authors: Bijlsma Anne M. E. , Assink Mark , Van der Put Claudia E.
Published: November 2022

Studies on child maltreatment prevention programs show that the effects of these programs are rather small. Drawing on the need principle of the Risk–Need–Responsivity model, program effects may be enhanced by properly assessing all the needs of individual families involved in child protection so that programs can be adapted to those needs. Recently, a needs assessment tool (ARIJ-Needs) has been developed in the Netherlands to support child protection practitioners in not only the assessment of treatment needs in individual families, but also in selecting the program(s) and/or intervention(s) that best target those needs. This study assessed the clinical value and usability of ARIJ-Needs by interviewing Dutch child protection practitioners (N = 15). A vignette describing a child protection case was used to examine differences between needs assessments based on unstructured clinical judgment (i.e., without using the assessment tool), and structured clinical judgment in which the assessment tool was used. The results showed that significantly more treatment needs were identified when ARIJ-Needs was used relative to clinical judgment in which ARIJ-Needs was not used. Specifically, needs related to parenting, the parent(s), and the family were identified more often when the assessment tool was used. This is an important finding, as these needs comprise the (changeable) risk factors that are most predictive of child maltreatment and should be addressed with priority to prevent child maltreatment. This study shows that ARIJ-Needs supports practitioners in assessing relevant needs in families at risk for child maltreatment. Study implications and recommendations for improvement of the ARIJ-Needs are discussed.
Data-Driven Model Selection for Compacted Graphite Iron Microstructure Prediction
Authors: Gumienny Grzegorz , Kacprzyk Barbara , Mrzygłód Barbara , Regulski Krzysztof
Published: November 2022

Compacted graphite iron (CGI), having a specific graphite form with a large matrix contact surface, is a unique casting material. This type of cast iron tends to favor direct ferritization and is characterized by a complex of very interesting properties. Intelligent computing tools such as artificial neural networks (ANNs) are used as predictive modeling tools, allowing their users to forecast the microstructure of the tested cast iron at the level of computer simulation. This paper presents the process of the development of a metamodel for the selection of a neural network appropriate for a specific chemical composition. Predefined models for the specific composition have better precision, and the initial selection provides the user with automation of reasoning and prediction. Automation of the prediction is based on the rules obtained from the decision tree, which classifies the type of microstructure. In turn, the type of microstructure was obtained by clustering objects of different chemical composition. The authors propose modeling the prediction of the volume fraction of phases in the CGI microstructure in a three-step procedure. In the first phase, k-means, unsupervised segmentation techniques were used to determine the metamodel (DT), which in the second phase enables the selection of the appropriate ANN submodel (third phase).
Electrochromic and Electrochemical Properties of Co3O4 Nanosheets Prepared by Hydrothermal Method
Authors: Yue Xinrui , Wang Gang , Wang Jing , Fan Licai , Hao Jian , Wang Shen , Yang Mingli , Liu Yang
Published: November 2022

In this paper, Co3O4 nanosheets were prepared by the hydrothermal method. The structure of the material was analyzed by morphological characterization and physical phase analysis, which confirmed the preparation of the product, Co3O4, showing a nanosheet structure. By studying the electrochromic properties of the prepared products, the results show that the transmittance modulation range of the Co3O4 nanosheet is 75% at 780 nm. The coloring response time and bleaching response time is about 3.8 s and 3.4 s, respectively. Electrochemical tests show that the Co3O4 nanosheets have good capacitive properties. Their specific capacitance reaches 1850 F/g when the current density is 1 A/g. When the current density is 5 A/g, the specific capacitance can still maintain 99.6% after 5000 cycles. In addition, Co3O4//CNTs devices can provide a maximum energy density of 79.52 Wh/kg (1 A/g) and a maximum power density of 11,000 W/kg (15 A/g), showing good energy storage capacity. The above data results indicate that the prepared Co3O4 nanosheets can be used as good candidates for supercapacitors. This paper provides a new idea and method for preparing Co3O4 materials.
Investigation of Facetted Growth in Heavily Doped Silicon Crystals Grown in Mirror Furnaces
Authors: Gruner Sebastian , Kranert Christian , Jauß Thomas , Sorgenfrei Tina , Reimann Christian , Friedrich Jochen
Published: November 2022

Herein, facets and related phenomena are studied for silicon crystals grown in the <100> and <111> directions, using the Zone Melting and Floating Zone techniques. Investigating the central facets of dislocation-free <111> crystals as a baseline allowed for the determination of the local temperature gradients. When comparing these results to dislocated <111> crystals, the presence of dislocations caused a clear reduction in the facet size, correlated with a reduction in the required local supercooling to estimated maximum values of around 0.6 K. Furthermore, for crystals grown on the rough {100} interface, attempts to provoke a morphological instability of the local phase boundary succeeded for crystallization velocities in the range of 10–16 mm/min, in good agreement with theory. Contrary to this observation, crystals grown in the <111> direction remained morphologically stable even at higher crystallization velocities due to the stabilizing effect of the atomically smooth interface. Additionally, crystals grown in the <111> direction with an oxygen skin by the Zone Melting technique reproducibly showed a non-periodic fluctuation of the central facet diameter at a certain translation velocity.
Chemical Cues Used by the Weevil Curculio chinensis in Attacking the Host Oil Plant Camellia oleifera
Authors: Qiu Hualong , Zhao Danyang , Fox Eduardo G. P. , Ling Siquan , Qin Changsheng , Xu Jinzhu
Published: November 2022

The weevil Curculio chinensis Chevrolat (Coleoptera: Curculionidae) is a major cause of economic losses to growers of Camellia oleifera in China, as females lay their eggs in developing fruits and the hatching larvae feed on their seed, aborting fruit growth. Olfactory cues play a key role in the host location of this weevil. The present study focused on identifying volatiles from different parts of the host plant Ca. oleifera, namely, the leaves, fruit peel, and seeds, and testing the antennal and behavioral responses of adult Cu. chinensis to those same volatiles. Methods relied on gas chromatography, electroantennograms, and Y-tube bioassays. The results included a total of twenty-five volatiles emitted by the three plant parts, among which eight elicited antennal responses in Cu. chinensis adults of both sexes. The behavioral bioassays indicated that 3-hexenal, trans-2-hexen-1-ol, methyl salicylate, geraniol, and phenethyl alcohol were attractive to Cu. chinensis, while trans-2-hexenal and 2-ethyl-1-hexanol were repellent. Tests with different concentrations indicated that the behavioral response could be dose-dependent. Future studies should focus on field tests with blends of the attractant compounds in order to develop novel, improved control methods for field applications.
Detection of Urinary Molecular Marker Test in Urothelial Cell Carcinoma: A Review of Methods and Accuracy
Authors: Bulai Catalin , Geavlete Petrisor , Ene Cosmin-Victor , Bulai Isabela , Popescu Razvan-Ionut , Mares Cristian , Ene Corina Daniela , Punga Ana-Maria , Geavlete Bogdan
Published: November 2022

Early detection of bladder cancer has a positive impact on prognosis. A variety of biomarkers have been developed to detect bladder tumors in urine early and reduce the need for cystoscopy. To detect bladder cancer, several methods are available, but their accuracy varies according to the sensitivity and specificity of each method. This review aims to highlight the established detection methods for bladder cancer based on the available literature. In addition, we aim to identify the combination of different effective detection methods that provides the highest degree of accuracy. In our study, a keyword retrieval method was used to search for appropriate English-language references. This bibliography has been indexed in PubMed and Scopus or has been found through systematic searches from 2015 to 2022. Based on an analysis of international guidelines, it has been revealed that there are numerous discrepancies and unresolved issues. The discovery of an ideal detection method for urothelial cell carcinoma biomarkers has been the subject of numerous efforts. In recent years, a wide range of off-label, experimental, novel, and combined approaches have been published on this topic. This review can contribute to the identification of accurate methods of detecting bladder cancer and highlight areas for future research that can be improved.
Diagnostics of Gastrointestinal Motility and Function: Update for Clinicians
Authors: Mari Amir
Published: November 2022

Disorders of gastrointestinal (GI) tract motility and function are prevalent in the general population and negatively affect quality of life [...]
Phenotypic Variation of Autosomal Recessive Leber Hereditary Optic Neuropathy (arLHON) in One Family
Authors: Pojda-Wilczek Dorota , Wójcik Justyna , Kmak Bożena , Krawczyński Maciej Robert
Published: November 2022

Leber hereditary optic neuropathy (LHON) is a rare disease with a prevalence of 1 in 25,000 births. LHON usually presents in young males, with painless loss of visual acuity in one or both eyes. Recently an autosomal recessive form of the disease (arLHON or LHONAR) has been described, which is caused by a biallelic mutation in the DNAJC30 gene (usually a missense mutation c.152A>G). The phenotypic and clinical characteristics of patients with arLHON are similar to those of mtLHON, but some differences have been described. Therapy is problematic and challenging. This paper describes clinical and electrophysiological findings in one family (three children and two parents) with arLHON and emphasizes the role of Photopic Negative Response Electroretinography, which provides objective measurement of retinal ganglion cells function. In Leber hereditary optic neuropathy, abnormal retinal ganglion cells function can be found in both eyes, even if visual acuity loss only occurs in one eye. Early clinical diagnosis, confirmed by genetic analysis, may be the key to sight-preserving treatment.