bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression
Authors: Maiso Patricia , Mogollón Pedro , Ocio Enrique M. , Garayoa Mercedes
Published: May 2021

Multiple myeloma (MM) is a hematological malignancy of plasma cells that proliferate and accumulate within the bone marrow (BM). Work from many groups has made evident that the complex microenvironment of the BM plays a crucial role in myeloma progression and response to therapeutic agents. Within the cellular components of the BM, we will specifically focus on mesenchymal stromal cells (MSCs), which are known to interact with myeloma cells and the other components of the BM through cell to cell, soluble factors and, as more recently evidenced, through extracellular vesicles. Multiple structural and functional abnormalities have been found when characterizing MSCs derived from myeloma patients (MM-MSCs) and comparing them to those from healthy donors (HD-MSCs). Other studies have identified differences in genomic, mRNA, microRNA, histone modification, and DNA methylation profiles. We discuss these distinctive features shaping MM-MSCs and propose a model for the transition from HD-MSCs to MM-MSCs as a consequence of the interaction with myeloma cells. Finally, we review the contribution of MM-MSCs to several aspects of myeloma pathology, specifically to myeloma growth and survival, drug resistance, dissemination and homing, myeloma bone disease, and the induction of a pro-inflammatory and immunosuppressive microenvironment.
Characterization of Renal Cell Carcinoma Heterotypic 3D Co-Cultures with Immune Cell Subsets
Authors: Rausch Magdalena , Blanc Léa , De Souza Silva Olga , Dormond Olivier , Griffioen Arjan W. , Nowak-Sliwinska Patrycja
Published: May 2021

Two-dimensional cell culture-based platforms are easy and reproducible, however, they do not resemble the heterotypic cell-cell interactions or the complex tumor microenvironment. These parameters influence the treatment response and the cancer cell fate. Platforms to study the efficacy of anti-cancer treatments and their impact on the tumor microenvironment are currently being developed. In this study, we established robust, reproducible, and easy-to-use short-term spheroid cultures to mimic clear cell renal cell carcinoma (ccRCC). These 3D co-cultures included human endothelial cells, fibroblasts, immune cell subsets, and ccRCC cell lines, both parental and sunitinib-resistant. During spheroid formation, cells induce the production and secretion of the extracellular matrix. We monitored immune cell infiltration, surface protein expression, and the response to a treatment showing that the immune cells infiltrated the spheroid co-cultures within 6 h. Treatment with an optimized drug combination or the small molecule-based targeted drug sunitinib increased immune cell infiltration significantly. Assessing the therapeutic potential of this drug combination in this platform, we revealed that the expression of PD-L1 increased in 3D co-cultures. The cost- and time-effective establishment of our 3D co-culture model and its application as a pre-clinical drug screening platform can facilitate the treatment validation and clinical translation.
Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma
Authors: Napoli Francesca , Listì Angela , Zambelli Vanessa , Witel Gianluca , Bironzo Paolo , Papotti Mauro , Volante Marco , Scagliotti Giorgio , Righi Luisella
Published: May 2021

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13–15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients’ genetic predisposition and tumor genomic profile. The chronic inflammatory response to asbestos fibers leads to a unique tumor immune microenvironment (TIME) composed of a heterogeneous mixture of stromal, endothelial, and immune cells, and relative composition and interaction among them is suggested to bear prognostic and therapeutic implications. TIME in MPM is known to be constituted by immunosuppressive cells, such as type 2 tumor-associated macrophages and T regulatory lymphocytes, plus the expression of several immunosuppressive factors, such as tumor-associated PD-L1. Several studies in recent years have contributed to achieve a greater understanding of the pathogenetic mechanisms in tumor development and pathobiology of TIME, that opens the way to new therapeutic strategies. The study of TIME is fundamental in identifying appropriate prognostic and predictive tissue biomarkers. In the present review, we summarize the current knowledge about the pathological characterization of TIME in MPM.
Radiomic Based Machine Learning Performance for a Three Class Problem in Neuro-Oncology: Time to Test the Waters?
Authors: Priya Sarv , Liu Yanan , Ward Caitlin , Le Nam H. , Soni Neetu , Pillenahalli Maheshwarappa Ravishankar , Monga Varun , Zhang Honghai , Sonka Milan , Bathla Girish
Published: May 2021

Prior radiomics studies have focused on two-class brain tumor classification, which limits generalizability. The performance of radiomics in differentiating the three most common malignant brain tumors (glioblastoma (GBM), primary central nervous system lymphoma (PCNSL), and metastatic disease) is assessed; factors affecting the model performance and usefulness of a single sequence versus multiparametric MRI (MP-MRI) remain largely unaddressed. This retrospective study included 253 patients (120 metastatic (lung and brain), 40 PCNSL, and 93 GBM). Radiomic features were extracted for whole a tumor mask (enhancing plus necrotic) and an edema mask (first pipeline), as well as for separate enhancing and necrotic and edema masks (second pipeline). Model performance was evaluated using MP-MRI, individual sequences, and the T1 contrast enhanced (T1-CE) sequence without the edema mask across 45 model/feature selection combinations. The second pipeline showed significantly high performance across all combinations (Brier score: 0.311–0.325). GBRM fit using the full feature set from the T1-CE sequence was the best model. The majority of the top models were built using a full feature set and inbuilt feature selection. No significant difference was seen between the top-performing models for MP-MRI (AUC 0.910) and T1-CE sequence with (AUC 0.908) and without edema masks (AUC 0.894). T1-CE is the single best sequence with comparable performance to that of multiparametric MRI (MP-MRI). Model performance varies based on tumor subregion and the combination of model/feature selection methods.
CO2 Self-Poisoning and Its Mitigation in CuO Catalyzed CO Oxidation: Determining and Speeding up the Rate-Determining Step
Authors: Cheng Kai , Zhao Songjian , Ren Jiazheng , Li Haoran , Chen Yongsheng
Published: May 2021

Cu-based catalysts are promising for CO oxidation applications with catalyst deactivation being a major barrier. We start with a CuO/Al2O3 catalyst and find that while the CO conversion decreases, CO2 accumulates and the average Cu chemical state stays the same. It suggests CO2 self-poisoning, i.e., CO2 desorption is the rate-determining step. Subsequently, experiments are performed to prove this hypothesis by showing (1) CO2 adsorption inhibits O2 adsorption, (2) complete desorption of CO2 regenerate the catalyst, (3) pre-adsorbed CO2 quenches catalyst activity which recovers during the reaction and (4) the apparent activation energy is consistent with CO2 desorption. It is further evidenced by using a stronger CO2 adsorbing support CeO2 to speed up CO2 desorption from the CuO sites resulting in a superior CuO/CeO2 catalyst. It provides an example for experimentally deciding and speeding up the rate-determining step in a catalytic reaction.
Integrated Utilization of Dairy Whey in Probiotic β-Galactosidase Production and Enzymatic Synthesis of Galacto-Oligosaccharides
Authors: Duan Feiyu , Zhao Renfei , Yang Jingyi , Xiao Min , Lu Lili
Published: May 2021

This work established an integrated utilization of dairy whey in β-galactosidase production from Lactobacillus bulgaricus and prebiotics synthesis by the probiotic enzyme. A cost-effective whey-based medium was newly developed for culturing Lactobacillus bulgaricus to produce β-galactosidase. The medium was optimized through response surface methodology (RSM) involving a series of statistical designs, such as the Plackett–Burman design, steepest ascent experiment, and central composite design. Under the optimized medium, the β-galactosidase activity of L. bulgaricus reached 2034 U/L, which was twice that produced from the traditional MRS medium. The cells of L. bulgaricus harvested from the whey-based medium were subsequently treated with lysozyme. The resulting crude enzyme was used as an efficient catalyst, which catalyzed the synthesis of the prebiotic galacto-oligosaccharides (GOS) in a high yield of 44.7% by using whey (200 g/L) as the substrate. The sugar mixture was further purified by activated charcoal adsorption, thereby yielding a high-purity level of 77.6% GOS.
Preparation of TiO2/Ag[BMIM]Cl Composites and Their Visible Light Photocatalytic Properties for the Degradation of Rhodamine B
Authors: Lin Xi , Li Yanxia
Published: May 2021

In order to degrade toxic pollutants such as dyes during the process of sewage treatment, considerable attention has been paid to photocatalytic technologies. In this paper, TiO2/Ag[BMIM]Cl (1-butyl-3-methyl imidazolium chloride ([BMIM]Cl)) nanocomposites were prepared with TiO2 as the carrier, silver ions as dopants and ionic liquids (IL) as modifiers. The morphologies, microstructures, crystalline structure and optical properties of the TiO2/Ag[BMIM]Cl nanospheres are investigated by transmission electron microscopy (TEM), X-ray diffraction (XRD), total organic carbon (TOC), and UV-vis diffuse reflectance spectrum (UV-vis DRS) techniques. The TiO2/Ag[BMIM]Cl nanocomposites can selectively degrade rhodamine B (Rh B) under visible light because of the unstable quaternary ammonium salt. The as-obtained nanocomposites exhibit better photocatalytic activity performance than pure TiO2, TiO2/IL, and TiO2/Ag+. The experimental results show that the Rh B degradation rate can reach 98.87% under optimized producing conditions by using the TiO2/Ag[BMIM]Cl composites as the catalyzer. It shows that simultaneous doping with silver ions and ionic liquids can significantly improve the photocatalytic activity of TiO2 in Rh B degradation, indicating the formation of photosensitive AgCl in the process of TiO2/Ag[BMIM]Cl preparation. Ag+ and IL addition exchange the band gap of TiO2 and lengthen the visible wavelength range of the composite. The material has the advantages of low cost, facile preparation and reusability with the excellent degradation effect of Rh B.
A Novel and Efficient Method for the Synthesis of Methyl (R)-10-Hydroxystearate and FAMEs from Sewage Scum
Authors: di Bitonto Luigi , D’Ambrosio Valeria , Pastore Carlo
Published: May 2021

In this work, the transesterification of methyl estolides (ME) extracted from the lipid component present in the sewage scum was investigated. Methyl 10-(R)-hydroxystearate (Me-10-HSA) and Fatty Acid Methyl Esters (FAMEs) were obtained in a single step. A three-level and four factorial Box–Behnken experimental design were used to study the effects of methanol amounts, catalyst, temperature, and reaction time on the transesterification reaction using aluminum chloride hexahydrate (AlCl3·6H2O) or hydrochloric acid (HCl) as catalysts. AlCl3·6H2O was found quite active as well as conventional homogeneous acid catalysts as HCl. In both cases, a complete conversion of ME into Me-10-HSA and FAMEs was observed. The products were isolated, quantified, and fully characterized. At the end of the process, Me-10-HSA (32.3%wt) was purified through a chromatographic separation and analyzed by NMR. The high enantiomeric excess (ee > 92%) of the R-enantiomer isomer opens a new scenario for the valorization of sewage scum.
Impact of the Cathode Layer Printing Process on the Performance of MEA Integrating PGM Free Catalyst
Authors: Toudret Pierre , Blachot Jean-François , Heitzmann Marie , Jacques Pierre-André
Published: May 2021

In this work, platinum group metal (PGM) free-based cathode active layers were prepared using different printing techniques. The membrane electrode assemblies (MEAs) integrate a PGM free catalyst based on Fe, N and C atoms at the cathode side. Scanning electron microscopy (SEM) images of MEA cross sections showed the strong impact of the fabrication process on the cathode structure, the porosity and the ionomer repartition. The MEAs were characterized in a 25 cm2 single cell using cyclic voltammetry under H2/N2. The performance of the MEAs and the double layer capacity of the cathodes were also shown to be linked to the process used. The comparison of the electrochemical accessible surface of the catalyst and of its surface area (SBET) led to the determination of a utilization factor. The coated membrane (CCM) made using the decal transfer process gives the best performances.
Stable Performance of Supported PdOx Catalyst on Mesoporous Silica-Alumina of Water Tolerance for Methane Combustion under Wet Conditions
Authors: Kim Minseok , Lim Suhyun , Kim Chansong , Shin Chae-Ho , Baik Joon Hyun , Suh Young-Woong
Published: May 2021

In methane combustion, water tolerance of Pd-based catalysts is quite critical for stable performance, because water is produced in situ and a water-containing feed is used under real conditions. Herein, water-tolerant mesoporous silica-alumina (H-MSA) was prepared by solvent deficient precipitation (SDP) using triethoxy(octyl)silane (TEOOS) and aluminum isopropoxide (AIP). The H-MSA was more tolerant to water than γ-alumina, mesoporous alumina (MA), and mesoporous silica-alumina (MSA) synthesized by using tetraethyl orthosilicate (TEOS), because of the silica present on the external particle surface. Moreover, it exhibited better textural properties, leading to higher dispersion of PdOx. The PdOx catalyst supported on H-MSA was quite durable in repeated temperature-programmed cycles and isothermal tests in the presence of water vapor, compared to the reference PdOx catalysts. The measured stability was attributed to the water tolerance, weak Lewis acidity, and penta-coordinated Al species of the H-MSA support, which was preferentially imparted when TEOOS was added for substitution of 5 mol% AIP for the synthesis of H-MSA. Therefore, the SDP method employed herein is useful in endowing supported PdOx catalysts with the water tolerance necessary for stable methane combustion performance under wet conditions.
EphA2 Interacts with Tim-4 through Association between Its FN3 Domain and the IgV Domain of Tim-4
Authors: Moon Byeongjin , Yang Susumin , Kim Kwangwoo , Lee Juyeon , Jeong Dongtak , Park Daeho
Published: May 2021

Tim-4 promotes the engulfment of apoptotic cells or exogenous particles by securing them on phagocytes. It is unable to transduce signals by itself but helps other engulfment receptors sense and internalize them. However, the identity of the engulfment receptors collaborating with Tim-4 is still incompletely understood. In this study, we searched for a candidate transmembrane protein with a FN3 domain, important for interaction with Tim-4, in silico and investigated whether it indeed interacts with Tim-4 and is involved in Tim-4-mediated phagocytosis. We found that EphA2 containing a FN3 domain in the extracellular region interacted with Tim-4, which was mediated by the IgV domain of Tim-4 and the FN3 domain of EphA2. Nevertheless, we found that EphA2 expression failed to alter Tim-4-mediated phagocytosis of apoptotic cells or polystyrene beads. Taken together, our findings suggest that EphA2, a new Tim-4 interacting protein, may intervene in a Tim-4-mediated cellular event even if it is not phagocytosis of endogenous or exogenous particles and vice versa.
Innate and Adaptive Immune Genes Associated with MERS-CoV Infection in Dromedaries
Authors: Lado Sara , Elbers Jean P. , Plasil Martin , Loney Tom , Weidinger Pia , Camp Jeremy V. , Kolodziejek Jolanta , Futas Jan , Kannan Dafalla A. , Orozco-terWengel Pablo , Horin Petr , Nowotny Norbert , Burger Pamela A.
Published: May 2021

The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.
Lack of Relationship between Fibrosis-Related Biomarkers and Cardiac Magnetic Resonance-Assessed Replacement and Interstitial Fibrosis in Dilated Cardiomyopathy
Authors: Rubiś Paweł , Dziewięcka Ewa , Szymańska Magdalena , Banyś Robert , Urbańczyk-Zawadzka Małgorzata , Krupiński Maciej , Mielnik Małgorzata , Wiśniowska-Śmiałek Sylwia , Karabinowska Aleksandra , Podolec Piotr , Winiarczyk Mateusz , Gliniak Matylda , Kaciczak Monika , Robak Jan , Karapetyan Arman , Wypasek Ewa
Published: May 2021

The relationship between circulating fibrosis-related molecules and magnetic resonance-assessed cardiac fibrosis in dilated cardiomyopathy (DCM) is poorly understood. To compare circulating biomarkers between DCM patients with high and low fibrosis burdens, we performed a prospective, single-center, observational study. The study population was composed of 100 DCM patients (87 male, mean age 45.2 ± 11.8 years, mean ejection fraction 29.7% ± 10.1%). Replacement fibrosis was quantified by means of late gadolinium enhancement (LGE), whereas interstitial fibrosis was assessed via extracellular volume (ECV). Plasma concentrations of cardiotrophin-1, growth differentiation factor-15, platelet-derived growth factor, procollagen I C-terminal propeptide, procollagen III N-terminal propeptide, and C-terminal telopeptide of type I collagen were measured. There were 44% patients with LGE and the median ECV was 27.7%. None of analyzed fibrosis serum biomarkers were associated with the LGE or ECV, whereas NT-proBNP was independently associated with both LGE and ECV, and troponin T was associated with ECV. None of the circulating fibrosis markers differentiated between DCM patients with and without replacement fibrosis, or patients stratified according to median ECV. However, cardiac-specific markers, such as NT-proBNP and hs-TnT, were associated with fibrosis. Levels of circulating markers of fibrosis seem to have no utility in the diagnosis and monitoring of cardiac fibrosis in DCM.
Crosstalk of Multi-Omics Platforms with Plants of Therapeutic Importance
Authors: Pandita Deepu , Pandita Anu , Wani Shabir Hussain , Abdelmohsen Shaimaa A. M. , Alyousef Haifa A. , Abdelbacki Ashraf M. M. , Al-Yafrasi Mohamed A. , Al-Mana Fahed A. , Elansary Hosam O.
Published: May 2021

From time immemorial, humans have exploited plants as a source of food and medicines. The World Health Organization (WHO) has recorded 21,000 plants with medicinal value out of 300,000 species available worldwide. The promising modern “multi-omics” platforms and tools have been proven as functional platforms able to endow us with comprehensive knowledge of the proteome, genome, transcriptome, and metabolome of medicinal plant systems so as to reveal the novel connected genetic (gene) pathways, proteins, regulator sequences and secondary metabolite (molecule) biosynthetic pathways of various drug and protein molecules from a variety of plants with therapeutic significance. This review paper endeavors to abridge the contemporary advancements in research areas of multi-omics and the information involved in decoding its prospective relevance to the utilization of plants with medicinal value in the present global scenario. The crosstalk of medicinal plants with genomics, transcriptomics, proteomics, and metabolomics approaches will be discussed.
Identification of a New Transcriptional Co-Regulator of STEAP1 in Ewing’s Sarcoma
Authors: Markey Fatu Badiane , Romero Brigette , Parashar Vijay , Batish Mona
Published: May 2021

Ewing’s sarcoma (ES) is caused by a chromosomal translocation leading to the formation of the fused EWSFLI1 gene, which codes for an aberrant transcription factor EWSFLI1. The transcriptional targets of EWSFLI1 have been viewed as promising and novel drug targets in the treatment of ES. One such target is six transmembrane epithelial antigen of the prostate 1 (STEAP1), a transmembrane protein that is upregulated by EWSFLI1 in ES. STEAP1 is a hallmark of tumor invasiveness and an indicator of tumor responsiveness to therapy. EWSFLI1 binds to the STEAP1 promoter region, but the mechanism of action by which it upregulates STEAP1 expression in ES is not entirely understood. Upon analysis of the STEAP1 promoter, we predicted two binding sites for NKX2.2, another crucial transcription factor involved in ES pathogenesis. We confirmed the interaction of NKX2.2 with the STEAP1 promoter using chromatin immunoprecipitation (ChIP) analysis. We used single-molecule RNA imaging, biochemical, and genetic studies to identify the novel role of NKX2.2 in regulating STEAP1 expression in ES. Our results show that NKX2.2 is a co-regulator of STEAP1 expression and functions by interacting with the STEAP1 promoter at sites proximal to the reported EWSFLI1 sites. The co-operative interaction of NKX2.2 with EWSFLI1 in regulating STEAP1 holds potential as a new target for therapeutic interventions for ES.
Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2
Authors: Ali Rizwan , Al Zahrani Hajar , Barhoumi Tlili , Alhallaj Alshaimaa , Mashhour Abdullah , Alshammari Musaad A. , Alshawakir Yasser A. , Baz Omar , Alanazi Abdullah H. , Khan Abdul Latif , Al Nikhli Hassan , Al Balwi Mohammed A. , Al Riyees Lolwah , Boudjelal Mohamed
Published: May 2021

In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2. This cell line is derived from a Saudi Arabian female breast cancer patient with invasive ductal carcinoma. Immunocytochemistry showed a significant ratio of the KAIMRC2 cells’ expressing key breast epithelial and cancer stem cells (CSCs) markers, including CD47, CD133, CD49f, CD44, and ALDH-1A1. Gene and protein expression analysis showed overexpression of ABC transporter and AKT-PI3Kinase as well as JAK/STAT signaling pathways. In contrast, the absence of the tumor suppressor genes p53 and p73 may explain their high proliferative index. The mice model also confirmed the tumorigenic potential of the KAIMRC2 cell line, and drug tolerance studies revealed few very potent candidates. Our results confirmed an aggressive phenotype with metastatic potential and cancer stem cell-like characteristics of the KAIMR2 cell line. Furthermore, we have also presented potent small molecule inhibitors, especially Ryuvidine, that can be further developed, alone or in synergy with other potent inhibitors, to target multiple cancer-related pathways.
Extracellularly Released Calreticulin Induced by Endoplasmic Reticulum Stress Impairs Syncytialization of Cytotrophoblast Model BeWo Cells
Authors: Iwahashi Naoyuki , Ikezaki Midori , Nishitsuji Kazuchika , Yamamoto Madoka , Matsuzaki Ibu , Kato Naoki , Takaoka Naoyuki , Taniguchi Mana , Murata Shin-ichi , Ino Kazuhiko , Ihara Yoshito
Published: May 2021

The pregnancy-specific syndrome preeclampsia is a major cause of maternal mortality throughout the world. The initial insult resulting in the development of preeclampsia is inadequate trophoblast invasion, which may lead to reduced maternal perfusion of the placenta and placental dysfunction, such as insufficient trophoblast syncytialization. Endoplasmic reticulum (ER) stress has been implicated in the pathology of preeclampsia and serves as the major risk factor. Our previous studies suggested critical roles of calreticulin (CRT), which is an ER-resident stress response protein, in extravillous trophoblast invasion and cytotrophoblast syncytialization. Here, we studied the mechanism by which ER stress exposes the placenta to the risk of preeclampsia. We found that CRT was upregulated in the serum samples, but not in the placental specimens, from preeclamptic women. By using BeWo cells, an established model of cytotrophoblasts that syncytialize in the presence of forskolin, we demonstrated that thapsigargin-induced ER stress caused extracellular release of CRT from BeWo cells and that the extracellular CRT suppressed forskolin-induced release of β-human chorionic gonadotropin and altered subcellular localization of E-cadherin, which is a key adhesion molecule associated with syncytialization. Our results together provide evidence that induction of ER stress leads to extracellular CRT release, which may contribute to placental dysfunction by suppressing cytotrophoblast syncytialization.
Immobilized Fluorescent Probes for Simultaneous Multiple Protease Detection
Authors: Milićević David , Hlaváč Jan
Published: May 2021

A new concept for simultaneous detection of two model proteases based on immobilized fluorescently labelled peptides was developed and evaluated. Each probe was composed of a carrier modified by poly(ethylene glycol) (PEG) chains, a specifically cleavable linker, and a fluorescent dye incorporated in the peptide tail. Based on a single excitation–double emission fluorescence response of liberated fluorophores caused by enzymatic cleavage, the presence of a single or both proteases in a mixture was unambiguously determined in an experimentally established concentration range. Among the tested solid supports, Rink Amide PEGA resin was recognized as the most suitable choice from the perspective of on-resin enzyme assays.
Colorimetric Aptasensor for Detecting Bacillus carboniphilus Using Aptamer Isolated with a Non-SELEX-Based Method
Authors: Kim Ho-Kyeong , Kim Hye-Ri , Yoon Su-Jin , Lee Kang-Bong , Kim Jungbae , Kim Byoung-Chan
Published: May 2021

B. carboniphilus is a naphtha-degradative strain (NDS) that uses hydrocarbons for its growth and causes microbiologically influenced corrosion (MIC) in naphtha pipelines. To date, there have been no studies on receptors or sensors for the detection of B. carboniphilus. We isolate B. carboniphilus-specific aptamers with a non-SELEX-based method, which employs repetitive cycles of centrifugation-based partitioning. The binding affinities of three aptamers are evaluated by obtaining their dissociation constants (Kd), which range from 13.2 to 26.3 nM. The BCA-05 aptamer with the lowest Kd value is employed for a two-stage label-free aptasensing platform to verify the aptamer selectivity using colorimetric detection of B. carboniphilus. This platform starts with the aptamer-bacteria binding step, and the concentration of residual aptamer after binding depends on the amount of the target bacteria. Then, the amount of separated residual aptamer determines the degree of salt-induced aggregation of gold nanoparticles (AuNPs), which results in a color change from red to blue. The AuNP color change is expressed as the ratio of absorbances at 630 and 520 nm (A630/A520). Under optimized conditions, this aptasensor shows reliable performance with a linear correlation in the range 104–107 CFU mL−1 and a limit of detection of 5 × 103 CFU mL−1.
Pyelonephritis in Pediatric Uropathic Patients: Differences from Community-Acquired Ones and Therapeutic Protocol Considerations. A 10-Year Single-Center Retrospective Study
Authors: Parente Giovanni , Gargano Tommaso , Pavia Stefania , Cordola Chiara , Vastano Marzia , Baccelli Francesco , Gallotta Giulia , Bruni Laura , Corvaglia Adelaide , Lima Mario
Published: May 2021

Pyelonephritis (PN) represents an important cause of morbidity in the pediatric population, especially in uropathic patients. The aim of the study is to demonstrate differences between PNs of uropathic patients and PNs acquired in community in terms of uropathogens involved and antibiotic sensitivity; moreover, to identify a proper empiric therapeutic strategy. A retrospective study was conducted on antibiograms on urine cultures from PNs in vesicoureteral reflux (VUR) patients admitted to pediatric surgery department and from PNs in not VUR patients admitted to Pediatric Emergency Unit between 2010 and 2020. We recorded 58 PNs in 33 patients affected by VUR and 112 PNs in the not VUR group. The mean age of not VUR patients at the PN episode was 1.3 ± 2.6 years (range: 20 days of life–3 years), and almost all the urine cultures, 111 (99.1%), isolated Gram-negative bacteria and rarely, 1 (0.9%), Gram-positive bacteria. The Gram-negative uropathogens isolated were Escherichia coli (97%), Proteus mirabilis (2%), and Klebsiella spp. (1%). The only Gram-positive bacteria isolated was an Enterococcus faecalis. As regards the antibiograms, 96% of not VUR PNs responded to beta-lactams, 99% to aminoglycosides, and 80% to sulfonamides. For the VUR group, mean age was 3.0 years ± 3.0 years (range: 9 days of life–11 years) and mean number of episodes per patient was 2.0 ± 1.0 (range: 1–5); 83% of PNs were by Gram-negatives bacteria vs. 17% by Gram-positive: the most important Gram-negative bacteria were Pseudomonas aeruginosa (44%), Escherichia coli (27%), and Klebsiella spp. (12%), while Enterococcus spp. determined 90% of Gram-positive UTIs. Regimen ampicillin/ceftazidime (success rate: 72.0%) was compared to ampicillin/amikacin (success rate of 83.0%): no statistically significant difference was found (p = 0.09). The pathogens of PNs in uropathic patients are different from those of community-acquired PNs, and clinicians should be aware of their peculiar antibiotic susceptibility. An empiric therapy based on the association ampicillin + ceftazidime is therefore suggested.
Feasibility of Race by Sex Intersectionality Research on Suicidality in the Adolescent Brain Cognitive Development (ABCD) Study
Authors: Assari Shervin , Boyce Shanika , Bazargan Mohsen
Published: May 2021

Intersectional research on childhood suicidality requires studies with a reliable and valid measure of suicidality, as well as a large sample size that shows some variability of suicidality across sex by race intersectional groups. Objectives: We aimed to investigate the feasibility of intersectionality research on childhood suicidality in the Adolescent Brain Cognitive Development (ABCD) study. We specifically explored the reliability and validity of the measure, sample size, and variability of suicidality across sex by race intersectional groups. Methods: We used cross-sectional data (wave 1) from the ABCD study, which sampled 9013 non-Hispanic white (NHW) or non-Hispanic black (NHB) children between the ages of 9 and 10 between years 2016 and 2018. Four intersectional groups were built based on race and sex: NHW males (n = 3554), NHW females (n = 3158), NHB males (n = 1164), and NHB females (n = 1137). Outcome measure was the count of suicidality symptoms, reflecting all positive history and symptoms of suicidal ideas, plans, and attempts. To validate our measure, we tested the correlation between our suicidality measure and depression and Child Behavior Checklist (CBCL) sub-scores. Cronbach alpha was calculated for reliability across each intersectional group. We also compared groups for suicidality. Results: We observed some suicidality history in observed 3.2% (n = 101) of NHW females, 4.9% (n = 175) of NHW males, 5.4% (n = 61) of NHB females, and 5.8% (n = 68) of NHB males. Our measure’s reliability was acceptable in all race by sex groups (Cronbach alpha higher than 0.70+ in all intersectional groups). Our measure was valid in all intersectional groups, documented by a positive correlation with depression and CBCL sub-scores. We could successfully model suicidality across sex by race groups, using multivariable models. Conclusion: Given the high sample size, reliability, and validity of the suicidality measure, variability of suicidality, it is feasible to investigate correlates of suicidality across race by sex intersections in the ABCD study. We also found evidence of higher suicidality in NHB than NHW children in the ABCD study. The ABCD rich data in domains of social context, self-report, schools, parenting, psychopathology, personality, and brain imaging provides a unique opportunity to study intersectional differences in neural circuits associated with youth suicidality.
Different Effects of the COVID-19 Pandemic on Exercise Indexes and Mood States Based on Sport Types, Exercise Dependency and Individual Characteristics
Authors: Aghababa Alireza , Badicu Georgian , Fathirezaie Zahra , Rohani Hadi , Nabilpour Maghsoud , Zamani Sani Seyed Hojjat , Khodadadeh Elham
Published: May 2021

Exercise indexes have been affected by the coronavirus disease 2019 (COVID-19) pandemic and its related restrictions among athletes. In the present study, we investigated the exercise frequency and intensity before and during the COVID-19 pandemic, and also current exercise dependency and mood state among non-contact individual, contact individual, and team sports athletes. A total of 1353 athletes from non-contact individual sports athletes (NCISA), contact individual sports athletes (CISA) and team sport athletes (TSA) participated; 45.4% of them were females that completed a series of self-rating questionnaires covering sociodemographic information, former and current exercise patterns, exercise dependency and mood states. NCISA had less exercise frequency than CISA, both before and during the COVID-19 pandemic, and NCISA had less exercise frequency than TSA during the COVID-19 pandemic. Regarding exercise intensity, CISA had higher scores than NCISA and TSA before the COVID-19 pandemic, and CISA had more exercise intensity than TSA during the COVID-19 pandemic. Frequency and intensity were reduced from before to during the COVID-19 pandemic in the three groups, except for TSA intensity. In addition, positive and negative mood states were correlated with exercise dependency. CISA were more discouraged and vigorous than NCISA and TSA, respectively. For NCISA, CISA, and TSA, ordinal regressions separately showed that adherence to quarantine and exercise dependency were better predictors of exercise indexes. Finally, exercise dependency subscales were different among sports, but it was not in exercise dependency itself. Although the decrease in exercise indexes was noticeable, there was no consistent pattern of change in exercise behavior in all sports. Additionally, during the COVID-19 pandemic, negative moods were predominant among all athletes. The results discussed are based on exercise nonparticipating, sport type, and affect regulation hypothesis.
The Effect of a 10-Week Physical Activity Programme on Fundamental Movement Skills in 3–4-Year-Old Children within Early Childhood Education Centres
Authors: Ali Ajmol , McLachlan Claire , Mugridge Owen , McLaughlin Tara , Conlon Cathryn , Clarke Linda
Published: May 2021

The objective of this study was to examine the effect of a 10-week physical activity (PA) programme, in early childhood education (ECE) settings, on 3 and 4-year-old children’s fundamental movement skills (FMS). A further aim was to examine FMS three-months post-intervention. The PA instructors delivered one 45 min session/week over 10 weeks, to 3- and 4-year-old children (n = 46), across four ECE centres. These sessions involved participation from ECE teachers. Children in the control group (CON; n = 20) received no PA classes and completed pre- and post-intervention assessments only. Locomotor (e.g., running/hopping) and object-control (e.g., kicking/throwing) skills were assessed using the Test for Gross Motor Development-2 (TGMD-2), before and after the intervention and, for the intervention group (EXP), at 3 months. Locomotor and object-control skills significantly improved in the EXP group, with typically no change in the CON group. The EXP group’s locomotor and object-control skills were maintained at 3 months. The 10-week PA intervention successfully improved 3- and 4-year-old children’s FMS.
Single Ventricle—A Comprehensive Review
Authors: Rao P. Syamasundar
Published: May 2021

In this paper, the author enumerates cardiac defects with a functionally single ventricle, summarizes single ventricle physiology, presents a summary of management strategies to address the single ventricle defects, goes over the steps of staged total cavo-pulmonary connection, cites the prevalence of inter-stage mortality, names the causes of inter-stage mortality, discusses strategies to address the inter-stage mortality, reviews post-Fontan issues, and introduces alternative approaches to Fontan circulation.
A Comparison of Doxorubicin-Resistant Colon Cancer LoVo and Leukemia HL60 Cells: Common Features, Different Underlying Mechanisms
Authors: Locatelli Laura , Cazzaniga Alessandra , Fedele Giorgia , Zocchi Monica , Scrimieri Roberta , Moscheni Claudia , Castiglioni Sara , Maier Jeanette A.
Published: May 2021

Chemoresistance causes cancer relapse and metastasis, thus remaining the major obstacle to cancer therapy. While some light has been shed on the underlying mechanisms, it is clear that chemoresistance is a multifaceted problem strictly interconnected with the high heterogeneity of neoplastic cells. We utilized two different human cell lines, i.e., LoVo colon cancer and promyelocytic leukemia HL60 cells sensitive and resistant to doxorubicin (DXR), largely used as a chemotherapeutic and frequently leading to chemoresistance. LoVo and HL60 resistant cells accumulate less reactive oxygen species by differently modulating the levels of some pro- and antioxidant proteins. Moreover, the content of intracellular magnesium, known to contribute to protect cells from oxidative stress, is increased in DXR-resistant LoVo through the upregulation of MagT1 and in DXR-resistant HL60 because of the overexpression of TRPM7. In addition, while no major differences in mitochondrial mass are observed in resistant HL60 and LoVo cells, fragmented mitochondria due to increased fission and decreased fusion are detected only in resistant LoVo cells. We conclude that DXR-resistant cells evolve adaptive mechanisms to survive DXR cytotoxicity by activating different molecular pathways.
Doubly Blinded: An Uncommon Cause of Acute Visual Loss Due to Orbital Compartment Syndrome
Authors: Sawalha Khalid , Nair Devi
Published: May 2021

A 68-year-old female patient with a past medical history of atrial fibrillation on anticoagulation regimen with Apixaban and Clopidogrel presented for her scheduled Watchman device implantation. The device was indicated as patient was high risk for falling. Successful implantation of the left atrial appendage device was carried out, and the patient was sent to the floor. One hour after the procedure, the patient started having left-sided diplopia along with severe eye pain. An immediate CT scan of the head showed left superior orbital mass, concerning for hematoma. Urgent left canthotomy with cantholysis was conducted bedside. However, despite early interventions, the patient’s vision was lost.
Consolidation and Adhesion of Pictorial Layers on a Stone Substrate. The Study Case of the Virgin with the Child from Palazzo Madama, in Turin
Authors: Negri Anita , Nervo Marco , Di Marcello Stefania , Castelli Daniele
Published: May 2021

The study and the restoration of a polychrome limestone statue representing the Virgin with the Child, from Palazzo Madama in Turin (NW Italy) offered interesting conservation issue related to the polychromy on stone. To preserve the pictorial layers, it was necessary to re-establish the cohesion among the different polychrome layers (original and repainted) and the adhesion between polychrome film and the stone substrate. Particular attention was paid to the choice of intervention materials, selected through a preliminary survey of the scientific literature, and then verified by laboratory tests (tape test, colorimetric test, and permeability test). The most suitable product should to be able to penetrate porosity, to consolidate the layers, to make the pictorial film adhere with the stone surface, and to avoid changes in the colour and in the permeability. The material chosen also had to ensure compatibility with the cleaning method that could only take place after the consolidation of the pictorial layers due to the problematic state of preservation. A range of products, characterised by their small particle size and low viscosity, was tested, and a micro-acrylic resin was selected and successfully applied on the polychromy of the sculpture.
Aluminum Powder Preparation for Additive Manufacturing Using Electrostatic Classification
Authors: Shinkaryov Alexander S. , Cherkasova Margarita V. , Pelevin Ivan A. , Ozherelkov Dmitriy Yu. , Chernyshikhin Stanislav V. , Kharitonova Natalia A. , Gromov Alexander A. , Nalivaiko Anton Yu.
Published: May 2021

This work aims to study the possibility of using an electrostatic drum-type separator to prepare a powder with a narrow size distribution curve for usage in additive manufacturing. The size distributions of the uncoated commercial aluminum powders ASP-30, ASP-22, and ASP-5 were analyzed. It was shown that the powders ASP-30 and ASP-22 have similar asymmetric distributions with a SPAN of 1.480 and 1.756, respectively. ASP-5 powder, in turn, has a narrow distribution with a SPAN of 0.869. ASP-30 powder was chosen for further experiment because, traditionally, separators are used to classify large-sized materials with particle size more than 100 μm. The optimal mode of electrostatic classification was proposed for the selected powder. Various classification methods, including centrifugal and electrostatic, were compared. The powders before and after classification were studied by XRD, SEM, TEM, and TG–DSC analyses. The obtained results showed that electrostatic classification does not lead to the formation of coatings on the processed powders. Electrostatic separation effectively narrows the particle size distribution, making it a suitable and valuable method to classify initial powders for additive manufacturing.
Effect of Precipitated Precursor on the Catalytic Performance of Mesoporous Carbon Supported CuO-ZnO Catalysts
Authors: Li Yandong , Liang Guangfen , Wang Chengrui , Fang Yanhong , Duan Huamei
Published: May 2021

As part of concepts for chemical energy storage of excess chemical energy produced from renewable sources, we investigated the performance of CuO/ZnO catalysts supported on mesoporous carbon to convert CO2 hydrogenation to methanol. In this work, mesoporous carbon was used as the catalyst support for CuO-ZnO catalysts. Four catalysts with different precipitated precursors were synthesized and analyzed by N2-physisorption, X-ray diffraction (XRD), thermogravimetric analysis (TG-DTG), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results show that catalyst CZ-in situ had the highest turnover frequency (TOF) (2.8 × 10−3 s−1) and methanol production rate (0.8 mmol g−1·h−1). The catalysts for co-precipitation of copper and zinc on carbon precursors are more active. Cu/ZnO domains that are accessible to the reactant gas are another reason for the catalysts being active. The Cu-ZnO interface is crucial to methanol catalyst activity.
Controlling Protein Crystallization by Free Energy Guided Design of Interactions at Crystal Contacts
Authors: Hermann Johannes , Bischoff Daniel , Grob Phillip , Janowski Robert , Hekmat Dariusch , Niessing Dierk , Zacharias Martin , Weuster-Botz Dirk
Published: May 2021

Protein crystallization can function as an effective method for protein purification or formulation. Such an application requires a comprehensive understanding of the intermolecular protein–protein interactions that drive and stabilize protein crystal formation to ensure a reproducible process. Using alcohol dehydrogenase from Lactobacillus brevis (LbADH) as a model system, we probed in our combined experimental and computational study the effect of residue substitutions at the protein crystal contacts on the crystallizability and the contact stability. Increased or decreased contact stability was calculated using molecular dynamics (MD) free energy simulations and showed excellent qualitative correlation with experimentally determined increased or decreased crystallizability. The MD simulations allowed us to trace back the changes to their physical origins at the atomic level. Engineered charge–charge interactions as well as engineered hydrophobic effects could be characterized and were found to improve crystallizability. For example, the simulations revealed a redesigning of a water mediated electrostatic interaction (“wet contact”) into a water depleted hydrophobic effect (“dry contact”) and the optimization of a weak hydrogen bonding contact towards a strong one. These findings explained the experimentally found improved crystallizability. Our study emphasizes that it is difficult to derive simple rules for engineering crystallizability but that free energy simulations could be a very useful tool for understanding the contribution of crystal contacts for stability and furthermore could help guide protein engineering strategies to enhance crystallization for technical purposes.
Preparation of Gradient Materials with Molten Salts Electrodeposition
Authors: Li Hui , Liang Jinglong , Yan Hongyan , Li Yungang , Wang Le
Published: May 2021

A new way of preparing W–Cu functional gradient materials (FGM) with molten salts electrodeposition is studied. The results show that, with the conditions of current density 70 mA·cm−2, electrodeposition temperature 700 °C and bidirectional pulse electrodepositing for 30 minutes (min), the Cu–Ni gradient layer prepared under this condition is widely used dense and smooth. Fundamental to the preparation of Cu–Ni functional gradient layer, Cu–Ni is used as a cathode to deposit W. Under the current density of 50 mA·cm−2, the time of 20 min, with bidirectional pulse electrodeposition, the Cu+Ni+W gradient layer has uniform composition gradient change and larger thickness. The W–Cu gradient materials prepared in this study have good cohesiveness. The addition of Ni would promote the inter-diffusion of Cu and W, and increase the diffusion coefficient significantly.