bluuebunny/crossref_metadata_2025_split huggingface dataset:
The strength of cytomorphology and efficacy of immuno‐cytochemistry in distinguishing hepatocellular carcinoma from its mimics on fine‐needle aspiration cytology
Authors: Chikhale Mangesh , Toi Pampa Ch , Siddaraju Neelaiah , Ananthakrishnan Ramesh 
Published: April 2021

AbstractBackgroundCytomorphologic distinction of hepatocellular carcinoma (HCC) from its mimics on fine‐needle aspiration cytology (FNAC) is often problematic. The present study evaluates the strength of cytomorphology and the utility of an immuno‐panel of arginase‐1, glypican‐3, HepPar‐1, thyroid transcription factor (TTF‐1) and CK‐19 in resolving this diagnostic issue.MethodsFNAC features of 71 nodular hepatic lesions were studied with an immunocyto/ histochemical (ICC/IHC) panel of arginase‐1, glypican‐3, HepPar‐1, TTF‐1 taking 10% positivity as “cut‐off.” Cytomorpholologic diagnoses were compared with diagnoses made on combined cytomorphologic and ICC/IHC approach.ResultsOf 71 cases, 32, 10 and 29 had histopathologic, cell block and clinico‐radiologic correlation respectively with 55 metastatic adenocarcinomas (MAC), 13 HCCs and one case each of hepatic adenoma (HA), cirrhotic nodule (CN) and intrahepatic cholangiocarcinoma (CC). Cytoplasmic positivity of HepPar‐1 and glypican‐3 were noted in 11/13 and 8/13 HCCs respectively; while only 3/13 and 1/13 HCCs revealed cytoplasmic positivity for arginase‐1 and TTF‐1 respectively. Benign hepatic lesions were negative for glypican‐3 and TTF‐1, but expressed both arginase‐1and HepPar‐1. Twenty‐one of 55 MACs and the lone case of CC were positive for CK‐19; however, all MACs and CC cases were negative for HepPar‐1, arginase‐1, glypican‐3 and TTF‐1. The immune‐panel had sensitivity, specificity and diagnostic accuracy of 100%, 88.9% and 90.6%, respectively, for differentiating HCC from its morphologic mimics.ConclusionThough a meticulous cytologic evaluation in conjunction with clinicoradiologic profile helps in distinguishing HCC from its benign and malignant mimics; an immunopanel of arginase‐1, glypican‐3, HepPar‐1, TTF‐1 and CK‐19 drastically improves the diagnostic accuracy.
Repurposing of FDA‐approved drugs as inhibitors of sterol C‐24 methyltransferase of Leishmania donovani to fight against leishmaniasis
Authors: Tabrez Shams , Rahman Fazlur , Ali Rahat , Muhammad Fida , Alshehri Bader Mohammed , Alaidarous Mohammed A. , Banawas Saeed , Dukhyil Abdul Aziz Bin , Rub Abdur 
Published: April 2021

AbstractLeishmaniasis is a vector‐borne disease caused by around 20 species of Leishmania. The main clinical forms of leishmaniasis are cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). VL is caused by Leishmania infantum in Central and South America, Mediterranean Basin, Middle East, and by L. donovani in Asia and Africa. Sterol C‐24 methyltransferase (LdSMT) of L. donovani is a transferase enzyme of the sterol biosynthesis pathway. This pathway is one of the major targets for drug developments in Leishmania. Due to insufficient evidence about the exact function of SMT inside the cell and the uniqueness of the SMT enzyme in the Leishmania parasites made it a significant target for an effective drug development approach. We performed virtual screening of the Food and Drug Administration (FDA)‐approved drug library against LdSMT and found simeprevir, an antiviral drug on top in the binding score. It showed a significant binding affinity with LdSMT. The binding was supported by hydrogen bonds and several other interactions. Simeprevir inhibited L. donovani growth of promastigotes with 50% inhibitory concentration (IC50) of 51.49 ± 5.87 μM. Further studies showed that simeprevir induced ROS generation in 44.7% of parasites at 125‐μM concentration. Here, we for the first time reported simeprevir as an antileishmanial lead molecule using a drug repurposing approach.
Left atrial structure and function of the amyloidogenic V122I transthyretin variant in elderly African Americans
Authors: Minamisawa Masatoshi , Inciardi Riccardo M. , Claggett Brian , Cuddy Sarah A.M. , Quarta Candida C. , Shah Amil M. , Dorbala Sharmila , Falk Rodney H. , Matsushita Kunihiro , Kitzman Dalane W. , Chen Lin Y. , Solomon Scott D. 
Published: April 2021

AbstractAimsAfrican‐American carriers of the transthyretin (TTR) valine‐to‐isoleucine substitution (V122I) are at increased risk of heart failure, yet many have relatively subtle abnormalities of left ventricular (LV) function. We sought to explore the influence of this mutation on left atrial (LA) structure and function in this population.Methods and resultsWe assessed 1225 genotyped African‐Americans (age range, 67–89 years) participating in the Atherosclerosis Risk in Communities study who underwent echocardiography and were in sinus rhythm at study Visit 5 (2011 to 2013). Six LA parameters [LA maximum/minimum volume index, ejection fraction, and LA reservoir, conduit, and contractile longitudinal strains (LS)] were compared between V122I TTR variant carriers (n = 46) and non‐carriers (n = 1179). LA minimum volume index was significantly greater and LA contractile LS was worse in carriers than non‐carriers (19.5 ± 10.6 mL/m2 vs. 16.3 ± 8.4 mL/m2; 15.0 ± 5.8% vs. 16.8 ± 5.7%, respectively, both P < 0.05). Carriers had a significantly higher number of LA abnormalities than non‐carriers (1.8 ± 2.2 vs. 1.1 ± 1.6, P = 0.009). The number of subjects with at least four LA abnormalities was significantly increased among carriers compared with non‐carriers (27% vs. 12%; odds ratio 2.43; 95% confidence interval 1.06–5.58 after adjusting for age, sex, body mass index, and LV wall thickness and global LS).ConclusionsLeft atrial enlargement and dysfunction were common in V122I TTR carriers with sinus rhythm than non‐carriers, suggesting that abnormalities of LA function may represent early markers of subclinical disease in these individuals.
JAK inhibitors: Ten years after
Authors: Spinelli Francesca Romana , Meylan Françoise , O'Shea John J. , Gadina Massimo 
Published: April 2021

AbstractThe European Journal of Immunology was launched 50 years ago, coinciding with the discovery of many cytokines and growth factors and the emergence of an entirely new field of research. Ultimately, our knowledge about the biological activity of these factors allowed us to better understand how the immune system functions in the context of inflammatory and autoimmune diseases leading to the development of targeted biologic therapies. The study of cytokine signal transduction led to the discovery of Janus kinases (JAK), and the consideration of therapeutically targeting JAKs to treat immune and inflammatory diseases. This year also marks the tenth anniversary of the approval of the first JAK inhibitor (jakinib) and now there are a total of nine approved jakinibs for treatment of rheumatologic, dermatologic, gastrointestinal, and neoplastic indications and most recently COVID‐19. Here, we summarized the discoveries that led to development of first‐generation jakinibs, discussed some of the newer, possibly more selective jakinibs, as well as jakinibs that also target other kinases. We also illustrated the rationale behind the application of these drugs in the treatment of COVID‐19 cytokine storm. In this review, we will discuss the clinical success of jakinibs, the gaps in our understanding of their biological activities as well as challenges in regard to their clinical application.
New Silver(I)‐P4 Coordination Polymers Strongly Adsorb Congo Red to Yield Composites with Enhanced Photocurrent Responses
Authors: Zhang Min , Feng Meng‐Yao , Yan Jia‐Jun , Li Hai‐Yan , Young David James , Li Hong‐Xi , Ren Zhi‐Gang 
Published: April 2021

AbstractReaction of tetraphosphine (P4) ligand dppbpda with Ag(I) oxylates yielded new coordination polymers (CPs) of formula [(dppbpda)Ag4(Ox)4]n (Ox=Bz (1), Sal (2), LA (3), Bz=benzoate, Sal=salicylate, LA=lactate). The solid‐state structures of 1–3 consist of one dimensional (1D) chains constructed from tetranuclear μ‐η2,η2‐ connected Ag4(Ox)4 cluster cores and dppbpda bridging ligands. Compounds 1–3 absorbed Congo Red in two distinct steps, with maximum uptake quantities of 1438 (1), 1417 (2) and 1656 (3) mg/g, inversely correlating with the size of the anions in the CPs. These CPs had band gaps in the semiconducting region (Eg) 3.05–3.15 eV and all three showed enhanced two‐peak photocurrent responses during the stepwise adsorption of CR, with maximum photocurrent densities of 227 (1), 163 (2) and 386 (3) μA cm−2 for composites with optimized dye coverage.
Location of Cu Atom in Au‐Based Nanocluster and Its Optical Properties
Authors: Ren Xiuqing , Fu Xuemei , Lin Xinzhang , Tang Jie , Wang He , Liu Chao , Huang Jiahui 
Published: April 2021

AbstractAtomically precise alloy nanoclusters are one of the important nanomaterials, benefiting to investigate the structure‐property correlations at atomic level. Herein, we reported Au19Cu2(SR)15(SR: adamantanethiol) alloy nanocluster. The crystal structure of Cu−Au nanoclusters was determined by X‐ray crystallography and the molecular mass was further characterized via Fourier transform ion cyclotron resonance mass spectrometer (FT‐ICR‐MS). The crystal structure shows the kernel of bi‐octahedrons Au10capped by a Au6Cu2(SR)9motif, a Au2(SR)3motif, a Au(SR)2motif and one S atom. It was observed that two Au atoms in the longest Au6Cu2(SR)9motif were replaced with two Cu atoms. Moreover, we explored optical properties of Au19Cu2(SR)15by UV‐vis absorption spectroscopy and fluorescence spectroscopy. Alloy nanocluster exhibits a strong emission at 700 nm. This work provides insights into the synthesis and the enhanced properties of Au−Cu alloy nanoclusters.
Determinants of Legacy Persistent Organic Pollutant Levels in the European Pond Turtle (Emys orbicularis) in the Camargue Wetland, France
Authors: Burkart Louisiane , Olivier Anthony , Lourdais Olivier , Vittecoq Marion , Blouin-Demers Gabriel , Alliot Fabrice , Le Gac Clément , Martin Nicolas , Goutte Aurélie 
Published: April 2021

Abstract
Many banned persistent organic pollutants (POPs) remain for decades in the aquatic environment and can have harmful effects on long-lived predators because of their high bioaccumulation and biomagnification potentials. We investigated the occurrence and levels of 18 polychlorinated biphenyls (PCBs) and 16 organochlorine pesticides in European pond turtles (n = 174) from April to July 2018 in the Camargue wetland, France. Although the Camargue was highly contaminated in previous decades, plasma occurrence and levels of POPs were very low: we were able to quantify only 3 of the 34 compounds we analyzed in &gt;10% of the turtles. The burdens from POPs did not differ between males and females and were uncorrelated with sampling date and body mass. We observed differences in POP burdens between turtles from the 2 sampling sites. One possible explanation is that the sampling sites were in different agricultural hydraulic systems: plasma occurrence and levels were higher for PCB-52 and hexachlorobenzene in turtles captured in drainage channels and for PCB-153 at the site that receives irrigation. Finally, the occurrence and levels of PCB-153 in turtles increased with age, likely because of bioaccumulation and much higher exposure 20 to 30 yr ago than now. Environ Toxicol Chem 2021;40:2261–2268. © 2021 SETAC
Deconvoluting Thermodynamics from Biology in the Aquatic Food Web Model
Authors: Ghosh Upal , Bokare Mandar , Gobas Frank A.P.C. 
Published: April 2021

Abstract
Bioaccumulation of hydrophobic pollutants in an aquatic food web is governed by exposure concentrations in sediment and water phases and by complex trophic interactions among the various species. We demonstrate that biological interactions and exposure from the chemical environment can be deconvoluted for aquatic food webs to allow clearer assessments of the role of thermodynamic drivers from the sediment and surface water phases. We first demonstrate the feasibility of this deconvolution mathematically for hypothetical food webs with 3 and 4 interacting species and for more realistic real-world food webs with &gt;10 species of aquatic organisms (i.e., the freshwater lake food web in Western Lake Erie [ON, Canada] and the marine food web in New Bedford Harbor [MA, USA]). Our results show both mathematically (for the simple food webs) and computationally (for the more complex food webs) that a deconvoluted food web model parameterized for site-specific conditions can predict the bioaccumulation of polychlorinated biphenyls in aquatic organisms same as existing complex food web models. The merit of this approach is that once the thermodynamic and biological contributions to food web bioaccumulation are computed for an ecosystem, the deconvoluted model provides a relatively simple approach for calculating concentrations of chemicals in organisms for a range of possible surface water and sedimentary concentrations. This approach is especially useful for calculating bioaccumulation of pollutants from freely dissolved concentrations measured using passive sampling devices or predicted by fate and transport models. The deconvoluted approach makes it possible to develop regulatory guidelines for a set of surface water and sediment (or porewater) concentration combinations for a water body that is able to achieve a risk-based target for fish concentration. Environ Toxicol Chem 2021;40:2145–2155. © 2021 SETAC.
Abstract
Thermodynamic influences of surface water and porewater separated mathematically from complex food web interactions. Csw and Cpw = dissolved concentrations of the hydrophobic organic contaminants in surface water and sediment porewater, respectively; fsw and fpw = fractional influence of surface water and porewater, respectively; BAFfish,A = bioaccumulation factor for Fish A.
Effect of temperature on mechanical properties of ultra‐high performance concrete
Authors: Banerji Srishti , Kodur Venkatesh 
Published: April 2021

SummaryHigh temperature mechanical property data are needed for evaluating fire resistance of structural members. Being a relatively new construction material, there is a lack of temperature‐dependent mechanical property data on ultra‐high performance concrete (UHPC). To address this knowledge gap, this paper presents results from an experimental study on the effect of temperature on mechanical properties of UHPC. Specimens made of two UHPC mixes: one with only steel fibers (UHPC‐S) and the other with hybrid fibers, that is, both steel and polypropylene (UHPC‐H), were tested under different heating conditions in 20 to 750°C temperature range. Compressive strength, tensile strength, stress‐strain response, and elastic modulus of UHPC were evaluated at various temperatures. Results generated from these property tests on UHPC were compared with property relations specified in design codes for conventional normal strength concrete (NSC) and high strength concrete (HSC). The comparisons show that UHPC experiences faster degradation in compressive strength and elastic modulus as compared to conventional concrete. However, UHPC exhibits slower degradation in tensile strength and ductility at elevated temperatures due to the presence of steel fibers. Data generated from these property tests were utilized to propose relations for expressing the mechanical properties of UHPC as a function of temperature and these relations can be used as input to numerical models for evaluating fire resistance of structures made of UHPC.
Chemical composition and biological activities of essential oils from Calendula officinalis L. flowers and leaves
Authors: Ak Gunes , Zengin Gokhan , Ceylan Ramazan , Fawzi Mahomoodally Mohamad , Jugreet Sharmeen , Mollica Adriano , Stefanucci Azzurra 
Published: April 2021

AbstractCalendula officinalis L., commonly known as pot marigold, is a popular ornamental and highly medicinal plant. In fact, it is well recognized for its wide‐ranging therapeutic effects conducive to wound healing and for treating various illnesses. In this study, the essential oils from flowers and leaves of C. officinalis were analysed for their chemical constituents and screened for their in vitro antioxidant and enzyme inhibitory properties. Thirty compounds were found in common in both essential oils, with the sesquiterpene alcohol, α‐cadinol as the most abundant compound (leaf: 32.3% and flower: 31.3%, respectively). Besides, the essential oils were found to possess antioxidant capacity through free radical scavenging and reducing mechanisms (DPPH: 2.94, 1.52 mg trolox equivalent (TE)/g of oil; ABTS: 20.72, 2.86 mg TE/g; CUPRAC: 31.16, 47.98 mg TE/g; FRAP: 24.84, 23.42 mg TE/g; phosphomolybdenum: 4.01, 4.68 mmol TE/g for leaves and flowers essential oils, respectively). Moreover, the essential oils (leaves and flowers, respectively) were found to inhibit all the tested enzymes, namely amylase (0.46, 0.42 mmol acarbose equivalent (ACAE)/g), glucosidase (1.35, 1.31 mmol ACAE/g), acetylcholinesterase (2.48, 2.36 mg galantamine (GALAE)/g) and butyrylcholinesterase (8.13, 8.20 mg GALAE/g) and tyrosinase (47.73, 54.36 mg kojic acid equivalent/g). Molecular docking was also performed revealing the compounds neophytadiene and α‐humulene to show the highest binding affinity with tyrosinase. Therefore, the obtained results demonstrated some appealing activities of C officinalis essential oils as natural pharmacological agents that could be valuable for the potential development of phyto‐formulations against the herein targeted diseases and especially for cosmeceutical applications.
Genomic and transcriptomic characterization of desmoplastic small round cell tumors
Authors: Sydow Saskia , Versleijen‐Jonkers Yvonne M. H. , Hansson Magnus , van Erp Anke E. M. , Hillebrandt‐Roeffen Melissa H. S. , van der Graaf Winette T. A. , Piccinelli Paul , Rissler Pehr , Flucke Uta E. , Mertens Fredrik 
Published: April 2021

AbstractDesmoplastic small round cell tumor (DSRCT) is a highly aggressive soft tissue tumor primarily affecting children and young adults. Most cases display a pathognomonic EWSR1‐WT1 gene fusion, presumably constituting the primary driver event. Little is, however, known about secondary genetic changes that may affect tumor progression. We here studied 25 samples from 19 DSRCT patients using single nucleotide polymorphism arrays and found that all samples had copy number alterations. The most common imbalances were gain of chromosomes/chromosome arms 1/1q and 5/5p and loss of 6/6q and 16/16q, all occurring in at least eight of the patients. Five cases showed homozygous deletions, affecting a variety of known tumor suppressor genes, for example, CDKN2A and NF1. As almost all patients died of their disease, the impact of individual imbalances on survival could not be evaluated. Global gene expression analysis using mRNA sequencing on fresh‐frozen samples from seven patients revealed a distinct transcriptomic profile, with enrichment of genes involved in neural differentiation. Two genes ‐ GJB2 and GAL ‐ that showed higher expression in DSRCT compared to control tumors could be further investigated for their potential as diagnostic markers at the protein level.
Asymmetric Hydrogenation: Design of Chiral Ligands and Transition Metal Complexes. Synthetic and Industrial Applications.
Authors: Genêt Jean‐Pierre , Phansavath Phannarath , Ratovelomanana‐Vidal Virginie 
Published: April 2021

AbstractThis personal account focuses on the development of atropisomeric ligands and chiral transition metal complexes and their applications to the asymmetric hydrogenation of alkenes, ketones and heteroaromatics using Ru(II) and Ir(III) catalysts in‐house developed. Particularly, effective scaled‐up development syntheses of SYNPHOS and DIFLUORPHOS have been successfully achieved and their steric and electronic profiling established. Going further, we demonstrated the utility of such homogeneous catalytic process highlighted with examples of industrial applications and total syntheses of biorelevant targets. Asymmetric hydrogenation provides a powerful tool for performing precise stereocontrolled transformations on valuable complex molecules.
Maternal death related to COVID‐19: A systematic review and meta‐analysis focused on maternal co‐morbidities and clinical characteristics
Authors: La Verde Marco , Riemma Gaetano , Torella Marco , Cianci Stefano , Savoia Fabiana , Licciardi Federico , Scida Serena , Morlando Maddalena , Colacurci Nicola , De Franciscis Pasquale 
Published: April 2021

AbstractBackgroundBesides reducing the quality of obstetric care, the direct impact of COVID‐19 on pregnancy and postpartum is uncertain.ObjectiveTo evaluate the characteristics of pregnant women who died due to COVID‐19.Search strategyCochrane Library, Embase, MEDLINE, Scopus, and Google Scholar were searched from inception to February 2021.Selection criteriaStudies that compared deceased and survived pregnant women with COVID‐19.Data collection and analysisRelevant data were extracted and tabulated. The primary outcome was maternal co‐morbidity.Main resultsThirteen studies with 154 deceased patients were included. Obesity doubled the risk of death (relative risk [RR] 2.48, 95% confidence interval [CI] 1.41–4.36, I2 = 0%). No differences were found for gestational diabetes (RR 5.71; 95% CI 0.77–42.44, I2 = 94%) or asthma (RR 2.05, 95% CI 0.81–5.15, I2 = 0%). Overall, at least one severe co‐morbidity showed a twofold increased risk of death (RR 2.26, 95% CI 1.77–2.89, I2 = 76%). Admission to intensive care was related to a fivefold increased risk of death (RR 5.09, 95% CI 2.00–12.98, I2 = 56%), with no difference in need for respiratory support (RR 0.53, 95% CI 0.23–1.48, I2 = 95%) or mechanical ventilation (RR 4.34, 95% CI 0.96–19.60, I2 = 58%).ConclusionCOVID‐19 with at least one co‐morbidity increases risk of intensive care and mortality.
Regulatory role of TIGAR on endothelial metabolism and angiogenesis
Authors: He Xiaochen , Zeng Heng , Cantrell Aubrey C. , Chen Jian‐Xiong 
Published: April 2021

AbstractEndothelial glycolytic metabolism plays an important role in the process of angiogenesis. TP53‐induced glycolysis and apoptosis regulator (TIGAR) is a significant mediator of cellular energy homeostasis. However, the role of TIGAR in endothelial metabolism, angiogenesis, and coronary flow reserve (CFR) has not been studied. The present study investigated whether knockout (KO) of TIGAR improves endothelial glycolytic function and angiogenesis. In vitro, aortic endothelial cells (ECs) from TIGAR KO mice exhibited increased expression of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase isoform‐3 (PFKFB3) and increased glycolytic function. These were accompanied by increased mitochondrial basal/maximal respiration and ATP production. Furthermore, knockout of TIGAR in ECs enhanced endothelial proliferation, migration, and tube formation. Knockout of TIGAR also significantly increased aortic sprouting ex vivo. In vivo, knockout of TIGAR increased the expression of proangiogenic factor, angiopoietin‐1 (Ang‐1) in mouse hearts. Knockout of TIGAR also significantly increased coronary capillary density with enhanced CFR in these hearts. Furthermore, TIGAR KO mice subjected to pressure overload (PO), a common model to study angiogenesis and cardiac hypertrophy, exhibited elevated expression of Ang‐1, VEGF, and PFKFB3 than that of the wild‐type (WT) mice. WT mice subjected to PO exhibited a significant reduction of coronary capillary density and impaired CFR, but TIGAR KO mice did not. In addition, knockout of TIGAR blunted TAC‐induced cardiac hypertrophy and dysfunction seen in the WT mice. In conclusion, knockout of TIGAR improves endothelial angiogenetic capabilities by enhancing the endothelial glycolytic function, mitochondrial respiration, and proangiogenic signaling, which leads to increased coronary capillary density and vascular function and protects against chronic stress.