bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deliberately Losing Control of C−H Activation Processes in the Design of Small‐Molecule‐Fragment Arrays Targeting Peroxisomal Metabolism
Authors: Khan Tareque Raysa , Hassell‐Hart Storm , Krojer Tobias , Bradley Anthony , Velupillai Srikannathasan , Talon Romain , Fairhead Michael , Day Iain J. , Bala Kamlesh , Felix Robert , Kemmitt Paul D. , Brennan Paul , von Delft Frank , Díaz Sáez Laura , Huber Kilian , Spencer John 
Published: August 2020

AbstractCombined photochemical arylation, “nuisance effect” (SNAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium‐throughput X‐ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho‐arylation of 2‐phenylpyridine gave five products resulting from mono‐ and bisarylations combined with SNAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.
First‐in‐human phase 1 study of MK‐1248, an anti–glucocorticoid‐induced tumor necrosis factor receptor agonist monoclonal antibody, as monotherapy or with pembrolizumab in patients with advanced solid tumors
Authors: Geva Ravit , Voskoboynik Mark , Dobrenkov Konstantin , Mayawala Kapil , Gwo Jennifer , Wnek Richard , Chartash Elliot , Long Georgina V. 
Published: August 2020

BackgroundLigation of glucocorticoid‐induced tumor necrosis factor receptor (GITR) decreases regulatory T cell–mediated suppression and enhances T‐cell proliferation, effector function, and survival. MK‐1248 is a humanized immunoglobulin G4 anti‐GITR monoclonal antibody agonist.MethodsIn patients with advanced solid tumors, MK‐1248 (starting dose, 0.12 mg) was tested alone and with pembrolizumab (200 mg) according to a 3 + 3 dose escalation design (ClinicalTrials.gov identifier NCT02553499); both treatments were administered intravenously every 3 weeks for ≤4 and ≤35 cycles, respectively. The safety and tolerability, maximum tolerated dose, and pharmacokinetics/pharmacodynamics were explored.ResultsTwenty patients received MK‐1248 monotherapy; 17 received combination therapy. The most frequent tumor types were colorectal cancer (n = 8), melanoma (n = 6), and renal cell carcinoma (n = 4). MK‐1248 was generally well tolerated at the maximum tested doses of 170 (monotherapy) and 60 mg (combination). No dose‐limiting toxicities (DLTs) or treatment‐related deaths occurred. Adverse events (AEs) occurred in 36 of the 37 patients (97%); the most common were vomiting (n = 13 [35%]), anemia (n = 10 [27%]), and decreased appetite (n = 10 [27%]). Grade 3 to 5 AEs occurred in 19 of the 37 patients (51%). Treatment‐related AEs occurred in 18 of the 37 patients (49%): 9 of the 20 patients (45%) on monotherapy and 9 of the 17 patients (53%) on combination therapy. Among the 17 patients receiving combination therapy, 1 achieved a complete response and 2 achieved a partial response, for an objective response rate of 18%; no patients achieved an objective response with monotherapy. The disease control rate (stable disease or better) was 15% with monotherapy and 41% with combination therapy.ConclusionsMK‐1248 was generally well tolerated at doses up to 170 (monotherapy) and 60 mg (combination), with no DLTs or treatment‐related deaths. Combination therapy provided limited antitumor responses.
Cytomorphology of primary pulmonary NUT carcinoma in different cytology preparations
Authors: Dutta Rimlee , Nambirajan Aruna , Mittal Saurabh , Roy‐Chowdhuri Sinchita , Jain Deepali 
Published: August 2020

BackgroundNUT carcinoma (NC) is an aggressive neoplasm that often presents with alarge tumor burden and metastases; cytology is frequently one of the primary diagnostic modalities. Primary pulmonary NCs are very rare and cytology descriptions are limited. The current study was performed to analyze the cytomorphological features of primary pulmonary NCs in different cytology samples and preparations.MethodsA total of 15 cytology specimens from 10 patients with primary pulmonary NCs diagnosed primarily on histology were retrieved and reviewed.ResultsFifteen cytology samples, including aspirates from primary (5 samples) and metastatic (5 samples) sites, sputum (1 sample), and effusions (4 samples), that were prepared as direct smears, centrifuged smears, and cell blocks were reviewed. Aspirate smears from all cases were cellular and demonstrated fragments and cohesive clusters of primitive tumor cells with scant cytoplasm, ovoid nuclei with coarse granular chromatin, and consistently conspicuous single nucleoli in a frequently neutrophil‐rich necrotic background with dispersed bare tumor nuclei. In fluid cytology, tight, 3‐dimensional tumor clusters and singly lying tumor cells were observed. Squamous differentiation in the form of sheets and singly lying polygonal tumor cells with abundant dense cytoplasm was noted focally in rare cases. The diagnoses during original sign‐outs were poorly differentiated carcinoma, poorly differentiated squamous cell carcinoma, and malignant small round cell tumor. NUT‐1 (NUT family member 1 protein) immunocytochemistry performed on cell blocks demonstrated characteristic speckled nuclear staining in tumor cells.ConclusionsPulmonary NC presents as a poorly differentiated carcinoma with focal to absent squamous differentiation on cytology. Cellular fragments of primitive tumor cells with conspicuous nucleoli should raise suspicion of NUT carcinoma and prompt ancillary testing.
A Self‐Assembling Tripeptide‐Based Fluorescence Bio‐Nanosensor
Authors: Miao Pandeng , Liu Zhongdong , Liang Man , Guo Jun , Wang Tegexibaiyin , Wang Liping , Zhang Feng 
Published: August 2020

AbstractA de novo tripeptide, YFF, can self‐assemble into fluorescent nanostructures under ultraviolet irradiation, and their fluorescence can be selectively quenched by copper ions. Copper ions can co‐assemble with YFF NPs into hierarchical nanostructures, and the quenched fluorescence can recover again with the addition of pyrophosphate (diphosphate, PPi), which is due to the robust interaction between copper ions and PPi. Based on this principle, a simple and cost‐effective alkaline phosphatase (ALP) biosensor has been built up by making use of the specific dephosphorylation of ALP to PPi, in which the coordinated copper ions can reversibly bind to PPi, thus quench and recover the fluorescence of tripeptide nanostructures. The fluorescence intensity correlated well to the concentration of Cu2+ (2–100 μM), PPi (0–500 μM) and ALP (0–500 U/L) i, respectively, and the corresponding limits of detection (LOD) are 1.29 μM, 0.77 μM and 1.84 U/L, respectively. The designed tripeptide‐based nanosensor also exhibits biocompatible, robust sensing performance in serum, indicating its great potential application for clinical diagnosis.
Evolutionary game analysis between businesses and consumers under the background of Internet rumors
Authors: Li Bowen , Li Hua , Sun Qiubai , Chen Xuebo 
Published: August 2020

SummaryIn order to analyze the behavior of businesses and consumers under the impact of Internet rumors, this study constructs an evolutionary game model between consumers and businesses based on the Evolutionary Game Model proposed by Smith and with the introduction of a new parameter, that is, the degree of psychological identity consumers have on businesses. By analyzing the equilibrium point and the Evolution Stability Strategy, it is concluded that: (i) When the cost of investigating rumors is greater than the additional income obtained after the investigation, businesses will choose negative response, while consumers' purchase will is decided by the relationship between the cost of investigation paid by consumers and the cost of searching for a substitute. (ii) When the cost for investigating rumors is less than the additional income obtained later, both the probability of positive response by businesses and the probability of purchasing by consumers are in direct proportion to the degree of psychological identity consumers have on businesses. Conclusions of this article will provide theories and references of decision‐making for businesses influenced by Internet rumors.
GPUAnimats—Simulating animats, an agent‐based, artificial life model on graphical processing units
Authors: Quach Dara Q. , Playne Daniel P. , Scogings Chris J. 
Published: August 2020

SummaryA parallel implementation of an agent‐based, artificial life model for graphical processing units (GPUs) is presented. The model represents predator‐prey populations as a collection of agents (animats) who act independently and interact with their environment and each other. Individual animat interactions include avoidance, mating, and hunting which contribute to emergent behavior in the system as a whole such as herd formation and defensive spirals. Computational simulations of the model exploring the behavior of the model are limited in size due to the large populations that may result from certain environments and rule combinations. Parallel methods for computing the model on GPUs and a CUDA implementation are presented and are shown to provide a significant performance improvement over existing sequential implementations without simplifying the model behavior. The reduced simulation run‐time can allow both larger systems to be computed and a wider range of rule combinations that may produce larger populations to be investigated in a feasible amount of time.
Self‐Assembly of Hollow Organic Nanotubes Driven by Arene Regioisomerism
Authors: Alegre‐Requena Juan V. , Herrera Raquel P. , Díaz Díaz David 
Published: August 2020

AbstractArene regioisomerism in low‐molecular‐weight gelators can be exploited as a tool to modulate the micro‐structures of the corresponding xerogel networks by using the three different possible substitution patterns ortho, meta and para. This aromatic regioisomer‐driven strategy has been used with a cholesterol‐based gelator to prepare hollow self‐assembled organic nanotubes (S‐ONTs) with inside and outside diameters of ca. 35 and 140 nm, respectively. Electron microscopy imaging and theoretical calculations were employed to rationalize the formation mechanism of these S‐ONTs. From the three possible regioisomers, only the ortho‐disubstituted cholesteryl‐based gelator showed the optimal angle and distance between substituents to afford the formation of the cyclic assemblies required for nanotube growth by assembling 30–40 units of the gelator. This study opens fascinating opportunities to expand the synthesis of controllable and unique microstructures by modulating geometrical parameters through aromatic regioisomers.
Photochemical Rearrangement of a 19‐Membered Azoxybenzocrown: Products and their Properties
Authors: Wagner‐Wysiecka Ewa , Szulc Paulina , Luboch Elżbieta , Chojnacki Jarosław , Szwarc‐Karabyka Katarzyna , Łukasik Natalia , Murawski Miłosz , Kosno Michał 
Published: August 2020

AbstractThe preparation and characterization of products of the chemical and photochemical rearrangements of a 19‐membered o,o′‐azoxybenzocrown are presented. In photochemical rearrangement, besides the expected product i. e. 19‐membered o‐hydroxy‐o,o′‐azobenzocrown (19‐o‐OH) obtained under defined conditions with 75 % yield, also other macrocyclic products were isolated and identified, namely: 19‐membered p‐hydroxy‐o,o′‐azobenzocrown (19‐p‐OH), 21‐membered o′‐hydroxy‐o,p′‐azobenzocrown (21‐o′‐OH) and 19‐membered macrocycle containing a 5‐membered ring bearing an aldehyde group (19‐al). The structures of two atypical products of the photochemical rearrangement – 21‐o′‐OH and 19‐al – were determined in the solid state by X‐ray analysis and in solution using NMR spectroscopy. Tautomeric equilibrium of the formed hydroxyazobenzocrowns and its change depending on acidity/basicity of the environment and alkali and alkaline earth metal cations complexation were studied using UV‐Vis spectrophotometry, spectrofluorimetry and 1H NMR spectroscopy.
Genomic selection of forage agronomic traits in winter wheat
Authors: Maulana Frank , Kim Ki‐Seung , Anderson Joshua D. , Sorrells Mark E. , Butler Twain J. , Liu Shuyu , Baenziger P. Stephen , Byrne Patrick F. , Ma Xue‐Feng 
Published: August 2020

AbstractGenomic selection (GS) can improve genetic gain of complex traits in plant breeding. Phenotyping agronomic traits of winter wheat (Triticum aestivum L.) for dual‐purpose use is expensive and time‐consuming. In this study, we compared the prediction accuracies of four GS models (RR‐BLUP, GBLUP, GAUSS, and BL) for forage yield (FY), plant height (PH) and heading date (HD) of the hard winter wheat diversity panel (n = 298) using random and stratified sampling methods. In addition, we determined the appropriate training population (TP) size and marker density for GS of the traits. Moderate to high prediction accuracies ranging from 0.66 to 0.69 for FY, 0.46 to 0.49 for PH, and 0.71 to 0.74 for HD were observed for the GS models. However, the sampling method had little or no impact on prediction accuracy. The RR‐BLUP, GBLUP, and GAUSS models produced slightly greater prediction accuracies than BL for all traits studied. Prediction accuracies increased with increasing TP size and marker density in all the GS models tested. However, increase of prediction accuracy started to plateau at nTP = 180 lines and 1,000; 1,500; or 3,000 SNPs suggesting that the minimum TP size and marker density were about 180 lines and 1,000 or more SNPs, depending on the model and trait. The impact of TP size on prediction accuracy was greater for RR‐BLUP, GAUSS, and GBLUP than for BL model. This study suggests that RR‐BLUP, GBLUP, and GAUSS are viable models for selecting the forage agronomic traits during dual‐purpose wheat breeding.
Impact of nitrogen source, fall fertilizers, and preventive fungicides on spring dead spot caused by Ophiosphaerella korrae and O. herpotricha
Authors: Tredway L. P. , Soika M. D. , Butler E. L. , Kerns J. P. 
Published: August 2020

AbstractThe effects of N source, fall fertilization, and preventive fungicides were evaluated in bermudagrass [Cynodon dactylon (L.) Pers.] artificially inoculated with Ophiosphaerella korrae and O. herpotricha, the most common spring dead spot (SDS) pathogens in the United States. The source of N applied to bermudagrass from May to August 2006–2008 had a significant effect on SDS symptoms appearing in the spring of 2007–2009. Ammonium sulfate [(NH4)2SO4] provided excellent suppression of O. herpotricha but had no effect on O. korrae, which was suppressed instead by calcium nitrate (CaNO3). More research is needed to determine the underlying mechanisms responsible for suppression of SDS with N sources and the potential role of Mn and Ca in development of the disease. Fall applications of K, S, gypsum, or dolomitic lime had no influence on SDS development. Preventive applications of propiconazole, propiconazole + azoxystrobin, tebuconazole, or fenarimol provided effective control of O. herpotricha but failed to provide significant suppression of O. korrae. The differential response of SDS pathogens to fertilization practices and preventive fungicide applications highlight the importance of pathogen identification in development of integrated management programs.
Influence of manganese availability on switchgrass and pearl millet biomass production
Authors: Guo Ying , Fritschi Felix B. 
Published: August 2020

AbstractManganese is an essential nutrient and plays key roles in photosynthetic processes, including in NAD‐malic enzyme (NAD‐ME)‐type C4 plants as an activator of NAD‐ME. However, little is known about the Mn requirements of switchgrass (Panicum virgatum L.). To study Mn requirements for optimum growth and biomass production, a lowland (‘Alamo’) and an upland (‘Cave‐in‐Rock’) switchgrass ecotype were grown with either washed sand, vermiculite, or perlite and fertilized with nutrient solutions ranging in [Mn] from 0 to 200 μM. In the perlite experiment, pearl millet [Pennisetum glaucum (L.) R. Br. ‘KGraze’] was also grown. Shoot [Mn] was highly responsive to increasing Mn in the nutrient solution. When grown in washed sand and vermiculite, tissue [Mn] remained above those normally considered deficient, even in the 0 μM Mn treatment, and no Mn treatment effects on biomass production were found. In perlite, end‐of‐season shoot [Mn] were <5 mg kg−1 in all entries when no Mn was supplied, and a decrease in biomass production compared with 10–25 μM Mn treatments was observed for Alamo and KGraze, but not for Cave‐in‐Rock. Relative chlorophyll contents of switchgrass were lower in the 0 μM Mn treatment than in other treatments late in the season, but in KGraze, they were low early in the season and increased throughout the season, resulting in less pronounced (but still significant) differences at late stages. Overall, results indicated that switchgrass and pearl millet respond differently to low Mn availability and that even low levels of shoot tissue [Mn] allow switchgrass to maintain biomass production.
Naphthalene Structures Derived from Lignins During Phenolation
Authors: Li Suxiang , Shi Lanlan , Wang Chen , Yue Fengxia , Lu Fachuang 
Published: August 2020

AbstractPhenolation is a commonly used method to improve the reactivity of lignin for various applications. In this study, resinol lignin models (syringaresinol and pinoresinol) and eucalyptus alkali lignin were treated under acid‐catalyzed phenolation conditions to investigate the products derived from resinol (β–β) structures of lignins. The phenolation products were characterized by means of GC‐MS and NMR spectroscopy following separation using flash chromatography and thin‐layer chromatography. A series of new naphthalene products were identified from phenolation of syringaresinol, and the corresponding guaiacyl analogs were also identified by GC‐MS. The C1−Cα bond of these resinol compounds was cleaved to release syringol or guaiacol during phenolation. In addition, diphenylmethane products formed from phenol or phenol and syringol/guaiacol were found in the phenolation products. Comparatively, more naphthalene products were obtained by phenolation from syringaresinol than those obtained from pinoresinol. HSQC NMR characterization of the phenolated alkali lignin revealed that naphthalene structures formed in the phenolated lignin.
Trans‐omic profiling between clinical phenoms and lipidomes among patients with different subtypes of lung cancer
Authors: Zhu Zhenhua , Zhang Linlin , Lv Jiapei , Liu Xiaoxia , Wang Xiangdong 
Published: August 2020

AbstractLung cancer has high mortality, often accompanied with systemic metabolic disorders. The present study aimed at defining values of trans‐nodules cross‐clinical phenomic and lipidomic network layers in patients with adenocarcinoma (ADC), squamous cell carcinomas, or small cell lung cancer (SCLC). We measured plasma lipidomic profiles of lung cancer patients and found that altered lipid panels and concentrations varied among lung cancer subtypes, genders, ages, stages, metastatic status, nutritional status, and clinical phenome severity. It was shown that phosphatidylethanolamine elements (36:2, 18:0/18:2, and 18:1/18:1) were SCLC specific, whereas lysophosphatidylcholine (20:1 and 22:0 sn‐position‐1) and phosphatidylcholine (19:0/19:0 and 19:0/21:2) were ADC specific. There were statistically more lipids declined in male, <60 ages, late stage, metastasis, or body mass index < 22 . Clinical trans‐omics analyses demonstrated that one phenome in lung cancer subtypes might be generated from multiple metabolic pathways and metabolites, whereas a metabolic pathway and metabolite could contribute to different phenomes among subtypes, although those needed to be furthermore confirmed by bigger studies including larger population of patients in multicenters. Thus, our data suggested that trans‐omic profiles between clinical phenomes and lipidomes might have the value to uncover the heterogeneity of lipid metabolism among lung cancer subtypes and to screen out phenome‐based lipid panels as subtype‐specific biomarkers.
Proliferative activity is disturbed in myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS), and MDS/MPN diseases. Differences between MDS and MDS/MPN
Authors: Mestrum Stefan G. C. , de Wit Norbert C. J. , Drent Roosmarie J. M. , Hopman Anton H. N. , Ramaekers Frans C. S. , Leers Math P. G. 
Published: August 2020

AbstractThe proliferation marker Ki‐67 is widely used within the field of diagnostic histopathology as a prognostic marker for solid cancers. However, Ki‐67 is hardly used for prognostic and diagnostic purposes in flow cytometric analyses of hematologic neoplasms. In the present study, we investigated to what extent the proliferative activity, as determined by Ki‐67 expression, is disturbed in myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS), and MDS/MPN diseases. Bone marrow aspirates from 74 patients suffering from MPN, MDS, or MDS/MPN, and aspirates from 50 non‐malignant cases were analyzed by flow cytometry for Ki‐67 expression in the erythro‐, myelo‐, and monopoiesis. Ki‐67 expression was used to investigate the proliferative activity during the various maturation steps within these hematopoietic cell lineages. In the MPN patient cohort, the proliferative activity of all cell lineages is significantly higher during almost all maturation stages compared to those of the benign control cohort. In the MDS and MDS/MPN cohort, a significantly lower proliferative activity is observed in the early maturation stages. In the MDS/MPN patient cohort, increased proliferative activity is seen in the later stages of the maturation. MDS and MDS/MPN display a distinct pattern in the proliferating fraction of maturing hematopoietic cells. This could become of added value in order to classify these malignancies based on their biological background and behavior, as well as in gaining a better understanding into the pathobiology of these malignancies.
Is pain temporary and glory forever? Detection of tramadol using dried blood spot in cycling competitions
Authors: Salamin Olivier , Garcia Arnaud , González‐Ruiz Víctor , Rossi Francesca , Bigard Xavier , Déglon Julien , Daali Youssef , Faiss Raphaël , Saugy Martial , Rudaz Serge 
Published: August 2020

AbstractTramadol is a synthetic opioid drug used in the treatment of chronic and acute pain. An abnormal prevalence of its misuse in elite sport to overcome pain resulting from prolonged physical effort was recently reported. However, besides its antinociceptive effects, tramadol consumption is associated with negative effects such as numbness, confusion, and reduced alertness. This fact prompted the Union Cycliste Internationale to ban the use of tramadol in cycling competitions. Herein, we present the development of a dried blood spot (DBS) sample collection and preparation method followed by a liquid‐chromatography mass spectrometry (LC‐MS) analysis to rapidly determine the presence of tramadol and its two main metabolites in blood samples. The detection window of each analyte was evaluated and the analysis of performance on various MS platforms (HRMS and MS/MS) was assessed. Tramadol and its two main metabolites were detected up to 12 h after the intake of a single dose of 50 mg of tramadol in positive controls. In professional cycling competitions, 711 DBS samples collected from 361 different riders were analysed using the developed methodology, but all returned negative results (absence of parent and both metabolite compounds). In the context of professional cycling, we illustrate a valid method bringing together the easiness of collection and minimal sample preparation required by DBS, yet affording the performance standards of MS determination. The proposed method to detect tramadol and its metabolites was successfully implemented in cycling races with a probable strong deterrent effect.