bluuebunny/crossref_metadata_2025_split huggingface dataset:
Untargeted Metabolomics Screen of Mid‐pregnancy Maternal Serum and Autism in Offspring
Authors: Ritz Beate , Yan Qi , Uppal Karan , Liew Zeyan , Cui Xin , Ling Chenxiao , Inoue Kosuke , von Ehrenstein Ondine , Walker Douglas I. , Jones Dean P. 
Published: June 2020

Discovering pathophysiologic networks in a blood‐based approach may help to generate valuable tools for early treatment or preventive measures in autism. To date targeted or untargeted metabolomics approaches to identify metabolic features and pathways affecting fetal neurodevelopment have rarely been applied to pregnancy samples, that is, an early period potentially relevant for the development of autism spectrum disorders (ASD). We conducted a population‐based study relying on autism diagnoses retrieved from California Department of Developmental Services record. After linking cases to and sampling controls from birth certificates, we retrieved stored maternal mid‐pregnancy serum samples collected as part of the California Prenatal Screening Program from the California Biobank for children born 2004 to 2010 in the central valley of California. We retrieved serum for 52 mothers whose children developed autism and 62 population controls originally selected from all eligible children matched by birth year and child's sex. Also, we required that these mothers were relatively low or unexposed to air pollution and select pesticides during early pregnancy. We identified differences in metabolite levels in several metabolic pathways, including glycosphingolipid biosynthesis and metabolism, N‐glycan and pyrimidine metabolism, bile acid pathways and, importantly, C21‐steroid hormone biosynthesis and metabolism. Disturbances in these pathways have been shown to be relevant for neurodevelopment in rare genetic syndromes or implicated in previous studies of autism. This study provides new insight into maternal mid‐pregnancy metabolic features possibly related to the development of autism and an incentive to explore whether these pathways and metabolites are useful for early diagnosis, treatment, or prevention.Lay SummaryThis study found that in mid‐pregnancy the blood of mothers who give birth to a child that develops autism has some characteristic features that are different from those of blood samples taken from control mothers. These features are related to biologic mechanisms that can affect fetal brain development. In the future, these insights may help identify biomarkers for early autism diagnosis and treatment or preventive measures. Autism Res 2020, 13: 1258–1269. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.
Autonomous Discovery of Materials for Intercalation Electrodes
Authors: Bölle Felix T. , Mathiesen Nicolai R. , Nielsen Alexander J. , Vegge Tejs , Garcia‐Lastra Juan Maria , Castelli Ivano E. 
Published: June 2020

AbstractInvited for this month's cover picture is the Section for Atomic Scale Materials Modelling led by Prof. Tejs Vegge at the Department of Energy Conversion and Storage, Technical University of Denmark. The cover picture illustrates an autonomous workflow, implemented in the framework of Density Functional Theory, designed to automatically calculate crucial properties for battery intercalation electrodes, including thermodynamic and mechanical stability, open circuit voltages (OCV), as well as kinetic barriers for the ionic transport. Applied here to identify cathode materials for Mg‐ion batteries, this workflow enables an accelerated discovery of intercalation battery electrodes. Read the full text of the Article at 10.1002/batt.201900152.
Human intestinal microbiota derived metabolism signature from a North American native botanical Oplopanax horridus with UPLC/Q‐TOF–MS analysis
Authors: Wang Chong‐Zhi , Wan Jin‐Yi , Wan Jingxuan , Wang Shilei , Luo Yun , Zeng Jinxiang , Yao Haiqiang , Zhang Chun‐Feng , Zhang Qi‐Hui , Sawadogo Wamtinga Richard , Xu Ming , Du Wei , Qi Lian‐Wen , Li Ping , Yuan Chun‐Su 
Published: June 2020

AbstractOplopanax horridus, widely distributed in North America, is an herbal medicine traditionally used by Pacific indigenous peoples for various medical conditions. After oral ingestion, constituents in O. horridus extract (OhE) could be converted to their metabolites by the enteric microbiome before absorption. In this study, in order to mimic gut environment, the OhE was biotransformed using the enteric microbiome of healthy human subjects. For accurate and reliable data collection with optimized approaches in sample preparation and analytical conditions, ultra‐performance liquid chromatography and quadrupole time‐of‐flight mass spectrometry were used to characterize parent constituents and their metabolites. In the extract, 20 parent compounds were identified including polyynes, sesquiterpenes, monoterpeondids, phenylpropanoids and phenolic acids. After the biotransformation, a total of 78 metabolites were identified, of which 37 belonged to polyynes metabolites. The common biotransformation pathways are hydroxylation, acetylization, methylation and demethylation. Based on the pathway distributions, the metabolism signature of OhE has been explored. The metabolism pathways of OhE compounds are dependent on their structural classifications and hydrophilic/hydrophobic properties. In summary, with comprehensive analysis, we systematically investigated human microbiome‐derived OhE metabolites. The enteric microbial metabolism signature provides novel information for future effective use of O. horridus.
Chemical Knockdown of MicroRNA with Small‐Molecule Chimeras
Authors: Feng Yi , Li Jinbo , Zhang Yan 
Published: June 2020

AbstractThis concept article introduces the emerging area of small‐molecule chimeras (SMCs) for knocking down microRNAs (miRNAs), which are endogenous gene silencers involved in diverse pathological processes. Compared with agents for genetic knockdown, small‐molecules hold significant promise in this field due to their ideal pharmacokinetic and pharmacodynamic properties. The SMCs introduced here are hetero‐bifunctional molecules comprising small‐molecule binders (SMBs) of miRNAs and chemical functionalities that either directly cleave RNAs or recruit ribonucleases to destroy RNAs. Binding of SMBs to miRNAs brings SMCs’ chemical functionalities close to the miRNA, eventually causing miRNA degradation. Compared with parent SMBs, SMCs exhibit remarkably enhanced potency and specificity in miRNA inhibition. The development and application of SMCs for miRNAs will be discussed.
Mechanisms of programmed cell death in the midgut and salivary glands fromBradysia hygida(Diptera: Sciaridae) during pupal–adult metamorphosis
Authors: de Cassia Santos Przepiura Thaylise , Navarro Aryelle M. , da Rosa Ribeiro Rafaela , Gomes José R. , Pitthan Karina V. , de Miranda Soares Maria A. 
Published: June 2020

AbstractProgrammed cell death is involved with the degeneration/remodeling of larval tissues and organs during holometabolous development. The midgut is a model to study the types of programmed cell death associated with metamorphosis because its structure while degenerating is a substrate for the formation of the adult organ. Another model is the salivary glands from dipteran because their elimination involves different cell death modes. This study aimed to investigate the models of programmed cell death operating during midgut replacement and salivary gland histolysis inBradysia hygida. We carried out experiments of real‐time observations, morphological analysis, glycogen detection, filamentous‐actin localization, and nuclear acridine orange staining. Our findings allow us to establish that an intact actin cytoskeleton is required for midgut replacement inB. hygidaand nuclear condensation and acridine orange staining precede the death of the larval cells. Salivary glands in histolysis present cytoplasmic blebbing, nuclear retraction, and acridine orange staining. This process can be partially reproduced in vitro. We propose that the larval midgut death involves autophagic and apoptotic features and apoptosis is a mechanism involved with salivary gland histolysis.
Simple and fast spectrophotometric method based on chemometrics for the measurement of multicomponent adsorption kinetics
Authors: Yang Xiaoxia , Muhammad Turghun , Bakri Mahinur , Muhammad Imran , Yang Jingjing , Zhai Honglin , Abdurahman Abdujelil , Wu Hailong 
Published: June 2020

AbstractUV–Vis spectrophotometry has been widely applied in the quantitative analysis of different analytes in many fields, but it still faces challenges in the analysis of multicomponent solutions due to strong spectral overlap and low selectivity. In this paper, UV–Vis spectrophotometric method combined with chemometrics algorithms was established for the simultaneous determination of liquid‐phase adsorption kinetics of multicomponent for the first time. Partial least squares (PLS), stepwise regression, and multiway PLS (N‐PLS) models were established by using the original spectrum and processed spectrum pretreated by two different methods. The prediction results were validated by high‐performance liquid chromatography (HPLC). N‐PLS model showed the best prediction ability and the prediction relative error was within 9%. Adsorption kinetics studies indicated that the pseudo‐second‐order model can describe the adsorption behavior of rutin and quercetin on AB‐8 resin more accurately. This method was fast, low cost, accurate and reliable, simple, and efficient for the determination of multicomponent liquid‐phase adsorption kinetics.
Ratiometric Detection of ATP by Fluorescent Cyclophanes with Bellows‐Type Sensing Mechanism
Authors: Agafontsev Aleksandr M. , Shumilova Tatiana A. , Oshchepkov Aleksandr S. , Hampel Frank , Kataev Evgeny A. 
Published: June 2020

AbstractPyrene‐based cyclophanes have been synthesized with the aim to realize a bellows‐type sensing mechanism for the ratiometric detection of nucleotide concentrations in a buffered aqueous solution. The sensing mechanism involves the encapsulation of a nucleobase between two pyrene rings, which affects the monomer‐excimer equilibrium of the receptor in the excited state. The nature of the spacer and its connection pattern to pyrene rings have been varied to achieve high selectivity for ATP. The 1,8‐substituted pyrene‐based cyclophane with the 2,2’‐diaminodiethylamine spacer demonstrates the best selectivity for ATP showing a 50‐fold increase in the monomer‐excimer emission ratio upon saturation with the nucleotide. The receptor can detect ATP within the biological concentrations range over a wide pH range. NMR and spectroscopic studies have revealed the importance of hydrogen bonding and stacking interactions for achieving a required receptor selectivity. The probe has been successfully applied for the real‐time monitoring of creatine kinase activity.
O‐GlcNAcase: Emerging Mechanism, Substrate Recognition and Small‐Molecule Inhibitors
Authors: Elbatrawy Ahmed A. , Kim Eun Ju , Nam Ghilsoo 
Published: June 2020

AbstractO‐GlcNAcylation is the dynamic and ubiquitous post‐translational glycosylation of nucleocytoplasmic proteins on serine/threonine residues; it is implicated in regulation of the cell cycle. This protein modification is mainly governed by a pair of enzymes: O‐GlcNAc transferase (OGT) adds the N‐acetylglucosamine moiety to acceptor proteins, and O‐GlcNAcase (OGA) hydrolyses the sugar moiety from protein acceptors. Irregular O‐GlcNAcylation is linked to several diseases including cancer, diabetes and neurodegeneration. Recently, the discovery of small‐molecule OGA inhibitors has enabled the physiological function of O‐GlcNAcylation to be investigated. However, the design of highly potent and selective inhibitors faces several challenges as no full structural data of human OGA has been discovered to date. Moreover, there are a number of mechanistically similar related enzymes such as β‐hexosaminidases (Hex), and the concomitant inhibition of these enzymes leads to undesirable lysosomal‐storage disorders. This review highlights recent insights into the structure of human O‐GlcNAcase and its isoforms. We focus on the catalytic mechanism and substrate recognition by OGA. In addition, it presents an updated overview of small‐molecule OGA inhibitors, with either carbohydrate or noncarbohydrate scaffolds. We discuss inhibitor structures, binding modes, and selectivity towards the enzyme, and potential outcomes in probing O‐GlcNAcylation at cellular levels.
Synthesis of Tetramic Acid Fragments Derived from Vancoresmycin Showing Inhibitory Effects towards S. aureus
Authors: Wingen Lukas Martin , Rausch Marvin , Schneider Tanja , Menche Dirk 
Published: June 2020

AbstractAn efficient route to various vancoresmycin‐type tetramic acids has been developed. The modular route is based on an effective Fries‐type rearrangement to introduce various appending acetyl residues. The minimum inhibitory concentration (MIC) values of the new tetramic acids against Staphylococcus aureus and Escherichia coli were determined, revealing that three of the new compounds exhibit antimicrobial activity against S. aureus. These bioactive compounds were structurally most closely related to the authentic vancoresmycin building block. Additionally, the compounds induced a lial‐lux bioreporter, which responds to cell wall stress induced by antibiotics that interfere with the lipid II biosynthesis cycle. These data suggest the tetramic acid moiety to be a part of the vancoresmycin pharmacophore.
Financial conflicts of interest among National Comprehensive Cancer Network clinical practice guideline panelists in 2019
Authors: Desai Aakash P. , Chengappa Madhuri , Go Ronald S. , Poonacha Thejaswi K. 
Published: June 2020

BackgroundClinical practice guidelines (CPGs) are evidence‐based guidelines that serve as a standard of care in oncology practice, reimbursements, and quality improvement initiatives. To our knowledge, the extent of financial conflicts of interest (FCOIs) in National Comprehensive Cancer Network (NCCN) guidelines have not been systemically evaluated. The current study evaluated the extent of FCOIs in the NCCN CPGs for the most common malignancies in the United States.MethodsThe authors examined the latest 2019 versions of the NCCN CPGs for the 10 most common cancers by incidence in the United States. Using disclosure lists, they catalogued the FCOIs for the panelists under various categories outlined in the CPG. The authors also tabulated the companies and institutions involved in each panel disclosure. An “episode” describes 1 instance of participation of a panelist in 1 company in 1 category of each guideline. “Affiliation” describes an industrial, commercial, or institutional affiliation reported by a panelist in each episode.ResultsOf the 491 panelists on the CPG panel, 483 (98.3%) completed FCOI disclosures. A total of 224 (46.4%) reported at least 1 FCOI episode. A total of 1103 episodes were disclosed with an average of 4.9 episodes reported per panelist with FCOIs. Acting as part of scientific advisory boards, as a consultant, or as an expert witness was the most common FCOI category (19.9%). A total of 191 companies were associated with 1103 episodes of FCOI. The top companies were Bristol‐Myers Squibb, Merck, Genentech, and AstraZeneca. Among cancers, the prevalence of FCOIs was highest for lung cancer (56%), bladder cancer (52%), pancreatic cancer (52%), non‐Hodgkin lymphoma (50%), kidney cancer (49%), colorectal cancer (43%), breast cancer (42%), melanoma (40%), prostate cancer (38%), and uterine cancer (32%). Among the panelists with FCOIs, 26%, 17%, and 57%, respectively, reported 1, 2, and >3 episodes. There were 127 episodes noted among the CPG chairs and/or vice chairs who reported FCOIs (mean, 6.4 episodes). The chairs and/or vice chairs of CPGs for uterine cancer, pancreatic cancer, melanoma, and prostate cancer were not found to have any FCOIs.ConclusionsFCOIs are very prevalent among NCCN CPG panelists. In nearly one‐half of the CPGs, the majority of the panelists had at least 1 FCOI. Greater than one‐half of the CPG chairs and/or vice chairs reported multiple FCOIs. Further research studies are necessary to determine the impact of these FCOIs.
Bis‐Selenoureas for Anion Binding: A 1H NMR and Theoretical Study
Authors: Picci Giacomo , Mocci Rita , Ciancaleoni Gianluca , Lippolis Vito , Zielińska‐Błajet Mariola , Caltagirone Claudia 
Published: June 2020

AbstractThe anion binding ability of a family of bis‐selenoureas L1‐L3 obtained by the reaction of 1,3‐bis(aminomethyl)‐benzene and phenylisoselenocyanate, p‐methoxyphenylisoselenocyanate and naphtylisoselenocyanate, for L1, L2, and L3, respectively, has been tested and compared to that of previously described bis‐urea analogues. Results suggest that the introduction of selenium leads to an increase in the acidity of the urea NH hydrogen atoms, and therefore to a stronger affinity (more than three‐fold higher) towards anion species, in particular dihydrogen phosphate, in DMSO‐d6. Theoretical calculations allowed for the optimization of the adducts receptors corroborating the experimental results.
Exome Sequencing Reveals Common and Rare Variants in F5 Associated With ACE Inhibitor and Angiotensin Receptor Blocker–Induced Angioedema
Authors: Maroteau Cyrielle , Siddiqui Moneeza Kalhan , Veluchamy Abirami , Carr Fiona , White Myra , Cassidy Andrew J. , Baranova Ekaterina V. , Rasmussen Eva R. , Eriksson Niclas , Bloch Katarzyna M. , Brown Nancy J. , Bygum Anette , Hallberg Par , Karawajczyk Malgorzata , Magnusson Patrik K. E. , Yue Qun‐Ying , Syvänen Ann‐Christine , von Buchwald Christian , Alfirevic Ana , Maitland‐van der Zee Anke H. , Wadelius Mia , Palmer Colin N. A. ,   PREDICTION‐ADR
Published: June 2020

Angioedema occurring in the head and neck region is a rare and sometimes life‐threatening adverse reaction to angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Few studies have investigated the association of common variants with this extreme reaction, but none have explored the combined influence of rare variants yet. Adjudicated cases of ACEI‐induced angioedema (ACEI‐AE) or ARB‐induced angioedema (ARB‐AE) and controls were recruited at five different centers. Sequencing of 1,066 samples (408 ACEI‐AE, ARB‐AE, and 658 controls) was performed using exome‐enriched sequence data. A common variant of the F5 gene that causes an increase in blood clotting (rs6025, p.Arg506Gln, also called factor V Leiden), was significantly associated with both ACEI‐AE and ARB‐AE (odds ratio: 2.85, 95% confidence interval (CI), 1.89–4.25). A burden test analysis of five rare missense variants in F5 was also found to be associated with ACEI‐AE or ARB‐AE, P = 2.09 × 10−3. A combined gene risk score of these variants, and the common variants rs6025 and rs6020, showed that individuals carrying at least one variant had 2.21 (95% CI, 1.49–3.27, P = 6.30 × 10−9) times the odds of having ACEI‐AE or ARB‐AE. The increased risk due to the common Leiden allele was confirmed in a genome‐wide association study from the United States. A high risk of angioedema was also observed for the rs6020 variant that is the main coagulation defect‐causing variant in black African and Asian populations. We found that deleterious missense variants in F5 are associated with an increased risk of ACEI‐AE or ARB‐AE.
Contribution of immunophenotype to the investigation and differential diagnosis of Burkitt lymphoma, double‐hit high‐grade B‐cell lymphoma, and single‐hit MYC‐rearranged diffuse large B‐cell lymphoma
Authors: Tsagarakis Nikolaos J. , Papadhimitriou Stefanos I. , Pavlidis Dimitris , Liapis Konstantinos , Gortzolidis Georgios , Kostopoulos Ioannis V. , Marinakis Theodoros , Paterakis Georgios 
Published: June 2020

AbstractBackgroundThere are no immunophenotypic guidelines for the investigation of MYC‐rearranged lymphomas. We aimed to identify simple immunophenotypic features that would help to differentiate between MYC‐rearranged lymphomas and guide cytogenetic analysis.MethodsWe reviewed diagnostic samples from patients diagnosed with Burkitt lymphoma (BL), double‐hit lymphoma (DHL), MYC‐rearranged diffuse large B‐cell lymphoma (MYC‐DLBCL), and standard (non‐MYC‐rearranged) DLBCL over the last decade in our Institution. Using flow cytometry (with antibodies CD20, CD10, CD38, bcl‐2, Ki‐67, FMC‐7, CD43, CD27, CD79b, CD23, and CD22) we determined antigen% expression and median‐fluorescence intensity ratios (MFIR). The forward scatter (FS) and side scatter (SS) characteristics of tumor B‐cells were compared with normal T‐cells (B/T ratios) for patients with MYC‐rearranged lymphomas.ResultsWe identified 51 patients of whom 14 had BL, 10 had DHL (6 MYC+/BCL2+; 4 MYC+/BCL6+), 8 MYC‐DLBCL, and 19 standard DLBCL. The significant differences (p <.05) were: higher CD38% in BL than standard DLBCL; higher CD10% in BL and DHL versus MYC‐DLBCL and standard DLBCL; higher CD10MFIR in BL than MYC‐DLBCL and standard DLBCL; higher Ki‐67% in BL than DHL and MYC‐DLBCL; higher bcl‐2% in DHL than BL; higher FMC‐7% in BL than MYC‐DLBCL and standard DLBCL; and lower SS (B/T) ratio in DHL than MYC‐DLBCL.ConclusionsThe combination of CD38% > 90, CD10% > 80, CD10MFIR > 10, bcl‐2% < 30, and Ki‐67% > 70 was characteristic of BL. “Deviation” from these cut‐offs should raise suspicion for DHL and, therefore, BCL2 and/or BCL6 FISH is required. We also found that a diagnosis of DHL rather than of MYC‐DLBCL was significantly associated with CD10% > 60, Ki‐67% > 50, and SS (B/T) <1.5.
Moderate early life stress improves adult zebrafish (Danio rerio) working memory but does not affect social and anxiety‐like responses
Authors: Fontana Barbara D. , Gibbon Alistair J. , Cleal Madeleine , Sudwarts Ari , Pritchett David , Miletto Petrazzini Maria Elena , Brennan Caroline H. , Parker Matthew O. 
Published: June 2020

AbstractEarly life stress (ELS) is defined as a short or chronic period of trauma, environmental or social deprivation, which can affect different neurochemical and behavioral patterns during adulthood. Zebrafish (Danio rerio) have been widely used as a model system to understand human neurodevelopmental disorders and display translationally relevant behavioral and stress‐regulating systems. In this study, we aimed to investigate the effects of moderate ELS by exposing young animals (6‐weeks postfertilization), for 3 consecutive days, to three stressors, and analyzing the impact of this on adult zebrafish behavior (16‐week postfertilization). The ELS impact in adults was assessed through analysis of performance on tests of unconditioned memory (free movement pattern Y‐maze test), exploratory and anxiety‐related task (novel tank diving test), and social cohesion (shoaling test). Here, we show for the first time that moderate ELS increases the number of alternations in turn‐direction compared to repetitions in the unconditioned Y‐maze task, suggesting increased working memory, but has no effect on shoal cohesion, locomotor profile, or anxiety‐like behavior. Overall, our data suggest that moderate ELS may be linked to adaptive flexibility which contributes to build “resilience” in adult zebrafish by improving working memory performance.