bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Insights into the Impact of Ecological Factor on Bioactivities and Phytochemical Composition of Paeonia veitchii
Authors: Yuan Meng , Yan Zhen‐Guo , Sun Dao‐Yang , Luo Xiao‐Ning , Xie Li‐Hang , Li Meng‐Chen , Wang Shu , Shi Qian‐Qian , Zhang Yan‐Long 
Published: November 2020

AbstractPaeonia veitchii has been widely distributed in China under different ecological types. Its roots contain diverse phytochemical constituents, which possess very high bioactivities. However, the influence of ecological factors on activities and ingredients of P. veitchii roots still remains unknown. The purpose of this research was to analyze the variation in bioactivities and phytochemical composition of P. veitchii roots upon exposure to various ecological factors. Seven P. veitchii populations collected from different regions in China were evaluated. The results of correlation analysis suggested that four major ecological factors, including average annual temperature, elevation, total potassium, and organic matter, had a strong correlation with the bioactivities of P. veitchii roots. Further, the major ecological factors were also highly correlated with the contents of naringin, gallic acid, benzoylpaeoniflorin, and paeoniflorin. The principal component analysis results supported four major metabolites as the main contributing ingredients. All populations were classified into three groups, G1, G2, and G3, through hierarchical cluster analysis. G1 showed more significant advantages in the above‐mentioned four ecological factors, four active ingredients, and bioactivities compared to the other two groups. P. veitchii roots growing at lower average annual temperature, high elevation, rich total potassium and organic matter in the soils were presumed to have relatively higher bioactivities. These data expand the study on the bioactivities and phytochemical composition of P. veitchii roots and have a guiding significance for the ecological factor selection during the cultivation process of this herbaceous peony species.
Osteogenic differentiation potential of human bone marrow‐derived mesenchymal stem cells enhanced by bacoside‐A
Authors: Ramesh Thiyagarajan 
Published: November 2020

Stem cell therapy is growing rapidly to treat numerous diseases including bone‐associated diseases. Mesenchymal stem cells (MSCs) are most commonly preferred to treat bone diseases because it possesses high osteogenic potency. Though, to obtain maximum osteogenic efficiency of MSCs is challenging. Therefore, this study was planned to evaluate the osteogenic efficiency of human bone marrow derived mesenchymal stem cells (hBMSCs) by bacoside‐A. This study was investigated the activity of alkaline phosphatase (ALP) and expressions of the genes specific to osteogenic regulation mainly runt‐related transcription factor 2 (Runx2), osterix (Osx), osteocalcin (OCN) and collagen type Iα1 (Col I α1) in hBMSCs cultured under osteogenic conditions at different concentrations of bacoside‐A for 14 days. The results of this study depicted significant upregulation in the activity of ALP and expressions of osteogenic regulator genes in bacoside‐A treated cells when compared with control cells. Besides, expressions of glycogen synthase kinase‐3β (GSK‐3β) and Wnt/β‐catenin were evaluated; these expressions were also significantly increased in bacoside‐A treated cells when compared with control cells. This result provides a further supporting evidence of bacoside‐A role on osteogenesis in hBMSCs. The present study suggest that bacoside‐A will be applied to ameliorate the process of osteogenesis in hBMSCs to repair damaged bone structure during MSC‐based therapy; this will be an excellent and auspicious treatment for bone‐associated disorders including osteoporosis.Significance of the studyOsteoporosis is a bone metabolic disorder characterized by an imbalance between the activity of osteoblastic bone formation and osteoclastic bone resorption that disrupts the bone microarchitecture. Current anti‐osteoporotic drugs are inhibiting bone resorption, but they are unable to restore the bone structure due to extreme bone remodelling process and causes numerous side effects. The finding of natural bioactive compounds with osteogenic property is very essential for osteoporosis treatment. This study was reported that bacoside‐A ameliorated osteogenic differentiation of hBMSCs through upregulation of osteogenic differentiation genes and Wnt/β‐catenin signalling pathway. This result is indicating that bacoside‐A may be useful for osteoporosis treatments.
Millisecond Allosteric Dynamics of Activated Ras Reproduced with a Slowly Hydrolyzable GTP Analogue
Authors: Chen Xiaomin , Gao Hexuan , Long Dong 
Published: November 2020

AbstractThe millisecond timescale dynamics of activated Ras transiently sample a low‐populated conformational state that has distinct surface property from the major state and represents a promising target for binding of small‐molecule compounds. To avoid the complications of hydrolysis, dynamics and other properties of active Ras have so far been routinely investigated by using non‐hydrolyzable GTP analogues, which, however, were previously reported to alter both the kinetics and distribution of the conformational exchange. In this study, we quantitatively measured and validated the internal dynamics of Ras complexed with a slowly hydrolyzable GTP analogue, GTPγS, which increases the lifetime of active Ras by 23 times relative to that of native GTP. It was found that GTPγS, in addition to its better mimicking of the exchange kinetics than the commonly used non‐hydrolyzable analogues GppNHp and GppCH2p, can rigorously reproduce the natural dynamics network in active Ras, thus indicating its fitness for use in the development of allosteric inhibitors.
The novel function of miR‐3195 for mutant PROK2 (c.223‐4C>A) degradation
Authors: Zhou Shasha , Li Pin 
Published: November 2020

AbstractKallmann syndrome (KS) is a rare human genetic disorder characterized by hypogonadotropic hypogonadism with the reduction or absence of olfactory sense. Mutations in multiple genes, including chemokine prokineticin‐2 (PROK2), are considered to contribute to the abnormal migration of gonadotropin‐releasing hormone neurons in the embryonic stage. However, the mechanisms of the different inheritance modes of KS have not been comprehensively determined. In this article, we present the case of one KS patient with the same mutation in PROK2 (c.223‐4C>A) as his mother. RNA sequencing analysis of his leukocytes showed a new transcript of PROK2, which contained a partial intron (192 bp) compared to those of his parents. Furthermore, we observed that hsa‐miR‐3195 was expressed at low levels in his and his father's sera compared to his mother's. Unexpectedly, hsa‐miR‐3195 was also identified to specifically target the 192 bp intron of the aberrant PROK2 transcript of this patient. We determined that high expression of hsa‐miR‐3195 could efficiently target aberrant PROK2 and stabilize the normal function of PROK2 in vitro, which provided a probable explanation for the different phenotypes of the patient and his mother with the same genotype.
Ectophosphatase activity in the triple‐negative breast cancer cell line MDA‐MB‐231
Authors: Lacerda‐Abreu Marco A. , Russo‐Abrahão Thais , Leite Tenório Aguiar Raíssa , Monteiro Robson de Queiroz , Rumjanek Franklin D. , Meyer‐Fernandes José R. 
Published: November 2020

AbstractBreast cancer is one of the most common cancers in the female population worldwide, and its development is thought to be associated with genetic mutations that lead to uncontrolled and accelerated growth of breast cells. This abnormal behavior requires extra energy, and indeed, tumor cells display a rewired energy metabolism compared to normal breast cells. Inorganic phosphate (Pi) is a glycolytic substrate of glyceraldehyde‐3‐phosphate dehydrogenase and has an important role in cancer cell proliferation. For cells to obtain Pi, ectoenzymes in the plasma membrane with their catalytic site facing the extracellular environment can hydrolyze phosphorylated molecules, and this is an initial and possibly limiting step for the uptake of Pi by carriers that behave as adjuvants in the process of energy harvesting and thus partially contributes to tumor energy requirements. In this study, the activity of an ectophosphatase in MDA‐MB‐231 cells was biochemically characterized, and the results showed that the activity of this enzyme was higher in the acidic pH range and that the enzyme had a Km = 4.5 ± 0.5 mM para‐nitrophenylphosphate and a Vmax = 2280 ± 158 nM × h−1 × mg protein−1. In addition, classical acid phosphatase inhibitors, including sodium orthovanadate, decreased enzymatic activity. Sodium orthovanadate was able to inhibit ectophosphatase activity while also inhibiting cell proliferation, adhesion, and migration, which are important processes in tumor progression, especially in metastatic breast cancer MDA‐MB‐231 cells that have higher ectophosphatase activity than MCF‐7 and MCF‐10 breast cells.
Angioimmunoblastic T‐cell lymphoma after acute myeloid leukemia: Alleged common pathogenesis. A case report and literature review
Authors: Iturrate Isabel , Loscertales Javier , Fernández‐Ruiz Elena , Muñoz Patricia , López Consuelo , del Campo Luciana , Muñoz Cecilia , Alegre Adrián 
Published: November 2020

AbstractThe genomic landscape of AITL is characterized by mutation of epigenetic modifiers. This gene expression pattern resembles myeloid diseases and shows a potential role for hypomethylating agents as possible therapy for AITL.
A 7‐week‐old male Golden Retriever with extreme leukocytosis: A case report
Authors: Bingham Emily , Conner Bobbi , Stern Jere , Vitalo Amber , Schaer Michael 
Published: November 2020

AbstractAlthough neoplasia should be a top concern for extreme leukocytosis in dogs, infectious causes must also be considered to avoid delays in treatment or undue recommendations for humane euthanasia. Blood film review is of paramount importance.
Confined Ru‐catalysts in a Two‐phase Heptane/Ionic Liquid Solution: Modeling Aspects
Authors: Kobayashi Takeshi , Kraus Hamzeh , Hansen Niels , Fyta Maria 
Published: November 2020

AbstractA modeling approach for atomic‐resolution studies of sup‐ ported ionic liquid phase (SILP) catalytic systems in silica mesoporous confinement with surface hydroxyl and functional groups is proposed. First, a force field for the Ru‐based catalyst is developed. Second, its solvation behavior within a bulk two‐phase system of heptane and an IL is studied. Third, static and dynamic properties of the confined system are investigated. Using classical molecular dynamics simulations, experimentally inaccessible properties can thus be studied that are important for an optimization of a SILP system for performing a ring‐closing metathesis reaction.
Understanding the Deactivation Pathways of Iridium(III) Pyridine‐Carboxiamide Catalysts for Formic Acid Dehydrogenation
Authors: Menendez Rodriguez Gabriel , Zaccaria Francesco , Tensi Leonardo , Zuccaccia Cristiano , Belanzoni Paola , Macchioni Alceo 
Published: November 2020

AbstractThe degradation pathways of highly active [Cp*Ir(κ2‐N,N‐R‐pica)Cl] catalysts (pica=picolinamidate; 1 R=H, 2 R=Me) for formic acid (FA) dehydrogenation were investigated by NMR spectroscopy and DFT calculations. Under acidic conditions (1 equiv. of HNO3), 2 undergoes partial protonation of the amide moiety, inducing rapid κ2‐N,N to κ2‐N,O ligand isomerization. Consistently, DFT modeling on the simpler complex 1 showed that the κ2‐N,N key intermediate of FA dehydrogenation (INH), bearing a N‐protonated pica, can easily transform into the κ2‐N,O analogue (INH2; ΔG≠≈11 kcal mol−1, ΔG ≈−5 kcal mol−1). Intramolecular hydrogen liberation from INH2 is predicted to be rather prohibitive (ΔG≠≈26 kcal mol−1, ΔG≈23 kcal mol−1), indicating that FA dehydrogenation should involve mostly κ2‐N,N intermediates, at least at relatively high pH. Under FA dehydrogenation conditions, 2 was progressively consumed, and the vast majority of the Ir centers (58 %) were eventually found in the form of Cp*‐complexes with a pyridine‐amine ligand. This likely derived from hydrogenation of the pyridine‐carboxiamide via a hemiaminal intermediate, which could also be detected. Clear evidence for ligand hydrogenation being the main degradation pathway also for 1 was obtained, as further confirmed by spectroscopic and catalytic tests on the independently synthesized degradation product 1 c. DFT calculations confirmed that this side reaction is kinetically and thermodynamically accessible.
Visible‐Light‐Promoted Formation of C—C and C—P Bonds Derived from Evolution of Bromoalkynes under Additive‐Free Conditions: Synthesis of 1,1‐Dibromo‐1‐en‐3‐ynes and Alkynylphosphine Oxides
Authors: Xu Hailong , Chen Rui , Ruan Hongjie , Ye Ruyi , Meng Ling‐Guo 
Published: November 2020

Main observation and conclusionThe controllable achievement of C—C and C—P bond formations is developed via visible‐light‐promoted bromoalkyne dimerization or its further transformation with secondary phosphine oxides. The 1,1‐dibromo‐1‐en‐3‐ynes are formed when bromoalkyne is exposed to visible‐light. While alkynylphosphine oxides are generated when bromoalkynes are mixed with secondary phosphine oxides.
The impact of serum concentration‐guided digoxin therapy on mortality of heart failure patients: A long‐term follow‐up, propensity‐matched cohort study
Authors: Muk Balázs , Vámos Máté , Bógyi Péter , Szabó Barna , Dékány Miklós , Vágány Dénes , Majoros Zsuzsanna , Borsányi Tünde , Duray Gábor Zoltán , Kiss Róbert Gábor , Nyolczas Noémi 
Published: November 2020

AbstractBackgroundRecently published studies suggested that digoxin may increase mortality in heart failure with reduced ejection fraction (HFrEF). However, in the vast majority of former trials serum digoxin concentration (SDC) was not measured and therapy was not SDC‐guided.AimTo assess the impact of SDC‐guided digoxin therapy on mortality in HFrEF patients.MethodsData of 580 HFrEF patients were retrospectively analyzed. In patients on digoxin, SDC was measured every 3 months and digoxin dosage was SDC‐guided (target SDC: 0.5‐0.9 ng/mL). All‐cause mortality of digoxin users and nonusers was compared after propensity score matching (PSM).ResultsAfter 7.1 ± 4.7 years follow‐up period (FUP) all‐cause mortality of digoxin users (n = 180) was significantly higher than nonusers (n = 297) (propensity‐adjusted HR = 1.430; 95% CI = 1.134‐1.804; P = .003). Patients having SDC of 0.9 to 1.1 ng/mL (n = 60) or > 1.1 ng/mL (n = 44) at any time during the FUP had an increased risk of all‐cause mortality (HR = 1.750; 95% CI = 1.257‐2.436, P = .001 and HR = 1.687; 95% CI = 1.153‐2.466, P = .007), while patients having a maximal SDC < 0.9 ng/mL (n = 76) had similar mortality risk (HR = 1.139; 95% CI = 0.827‐1.570, P = .426), compared to digoxin nonusers.ConclusionsAccording to our propensity‐matched analysis, SDC‐guided digoxin therapy was associated with increased all‐cause mortality in optimally treated HFrEF patients, especially with SDC ≥0.9 ng/mL. These results reinforce the expert opinion that digoxin in HFrEF can only be used among carefully selected patients with close SDC monitoring.
Hybrid Quinazoline 1,3,5‐Triazines as Epidermal Growth Factor Receptor (EGFR) Inhibitors with Anticancer Activity: Design, Synthesis, and Computational Study
Authors: Pathak Prateek , Rimac Hrvoje , Grishina Maria , Verma Amita , Potemkin Vladimir 
Published: November 2020

AbstractWe report a series of hybrid quinazoline‐1,3,5‐triazine derivatives as EGFR inhibitors, which were synthesised and tested by using a variety of in vitro, in silico, and in vivo techniques. The derivatives were found to be active against different cancer cell lines and nontoxic against normal ones, with compounds 7 c, 7 d, 7 e, and 7 j being the most potent ones. The derivatives were also evaluated for angiogenesis inhibition potency in chicken eggs, and molecular docking and dynamics simulation studies were carried out to elucidate the fundamental substituent groups essential for their bioactivity. Additionally, a SAR study of the derivatives was performed for future compound optimisation. These studies suggested that the derivatives have a high affinity towards EGFR with favourable pharmacological properties. The most active compound (7 e) was further evaluated for in vivo anticancer activity against DMBA‐induced tumours in female Sprague‐Dawley rats as well as its effects on plasma antioxidant status, biotransformation enzymes, and lipid profile. The study suggested that 7 e has lead properties against breast cancer and can serve as a starting compound for further development of anti‐EGFR compounds.
Long‐term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab
Authors: Topp Max S. , Gökbuget Nicola , Zugmaier Gerhard , Stein Anthony S. , Dombret Hervé , Chen Yuqi , Ribera Josep‐Maria , Bargou Ralf C. , Horst Heinz‐August , Kantarjian Hagop M. 
Published: November 2020

BackgroundBlinatumomab is a CD19 BiTE (bispecific T‐cell engager) immuno‐oncology therapy that mediates the lysis of cells expressing CD19.MethodsA pooled analysis of long‐term follow‐up data from 2 phase 2 studies that evaluated blinatumomab in heavily pretreated adults with Philadelphia chromosome–negative, relapsed/refractory B‐cell precursor acute lymphoblastic leukemia was conducted.ResultsA total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5‐8.5 months); the median follow‐up time for OS was 36.0 months (range, 0.3‐60.8 months). The median relapse‐free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2‐10.0 months); the median follow‐up time for RFS was 35.0 months (range, 9.5‐59.5 months). OS and RFS plateaued with 3‐year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3‐year relapse rate of 59.3%. For patients who achieved a CR/CRh with blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3‐30.0 months) with a 3‐year survival rate of 37.2%.ConclusionsThese data suggest that long‐term survival is possible after blinatumomab therapy.Lay Summary

Immuno‐oncology therapies such as blinatumomab activate the patient's own immune system to kill cancer cells.

This study combined follow‐up data from 2 blinatumomab‐related clinical trials to evaluate long‐term survival in patients with relapsed and/or refractory B‐cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes.

Among patients who achieved a deep response with blinatumomab, one‐third lived 3 years or longer. These findings suggest that long‐term survival is possible after treatment with blinatumomab.
Energy Relay Enhances Switching Efficiency in a Dendrimer–Azobenzene Supramolecular Assembly with an Anion–π Motif
Authors: Rahaman Sk. Atiur , Sahid Hossain Munshi , Hatai Joydev , Bandyopadhyay Subhajit 
Published: November 2020

AbstractTransformation of light energy into chemical energy through supramolecular assemblies is a major pathway for energy harvesting in natural systems. An anionic azobenzene photoswitch assembled with a light‐absorbing dendrimer via non‐covalent interactions such as anion‐π motifs transfer the absorbed light to the bound photoswitch. The energy transfer was used fortrans→cisphotoisomerization of the photoswitchable system. The photoisomerization rate in the dendrimer−azobenzene assembly was found to be faster compared to the azobenzene itself.
Theoretical Study on Singlet Fission Dynamics in Pentacene Ring‐Shaped Aggregate Models with Different Configurations
Authors: Miyamoto Hajime , Nakano Masayoshi 
Published: November 2020

AbstractThe front cover artwork is provided by the Nakano group at the Graduate School of Engineering Science, Osaka University (Japan). The image shows the singlet fission (SF) of pentacene J‐ and H‐ring‐shaped aggregates. Their SF rates exhibit mutually different size dependences, which are explained by relative relaxation factor and point group symmetry analysis. Read the full text of the Article at 10.1002/cptc.2020000089.
Performance of Ventana SP263 PD‐L1 assay in endobronchial ultrasound guided‐fine‐needle aspiration derived non‐small‐cell lung carcinoma samples
Authors: Chauhan Aastha , Siegel Lianne , Freese Rebecca , Racila Emilian , Stewart Jimmie , Amin Khalid 
Published: November 2020

AbstractBackgroundIntroduction of programmed death‐ligand 1 (PD‐L1) inhibitors has significantly changed the treatment landscape of non‐small‐cell lung carcinomas (NSCLC). Since endobronchial ultrasound guided fine‐needle aspiration (EBUS FNA) has become the primary diagnostic and staging modality for NSCLC, this study was pursued to determine the adequacy of Ventana SP263 PD‐L1 assay in cytology cell blocks.DesignFifty NSCLC cases with cytology and corresponding histology specimens obtained between 2014 and 2018 were identified. After assessing for adequacy (100 or more tumor cells), forty cases were selected for Ventana SP263 PD‐L1 immunohistochemistry (IHC) assay and assessed for tumor proportion scores (TPS) and staining intensity scores (SIS) and analyzed for concordance.ResultsOf the 40 matched pairs 33 (82.5%) showed concordant PD‐L1 expression. On cytology, 32 cases were positive (8 high‐expressors and 24 low‐expressors) of which 27 were concordant and 5 discordant with matched histology specimens. On histology, 29 cases were positive (7 high‐expressor and 22 low‐expressors) while 11 cases were negative for PD‐L1 expression of which 6 had concordant negative cytology. The intraclass correlation coefficients (ICC) for TPS was 0.81 with 95% confidence interval (0.68, 0.9) and for the SIS, it was 0.78 with 95% CI (0.62, 0.88), both considered as having excellent agreement.ConclusionWith an overall concordance rate of 82.5% between cytology and histology specimen, this study demonstrates the feasibility of PD‐L1 IHC with SP263 clone on cytology samples of NSCLC and adds to a growing body of evidence validating the use of cytology cell blocks for PD‐L1 expression testing.
Where’s wallaby? Using public records and media reports to describe the status of red‐necked wallabies in Britain
Authors: English Holly M. , Caravaggi Anthony 
Published: November 2020

AbstractInvestigating the range and population dynamics of introduced species provides insight into species behavior, habitat preferences, and potential of becoming established. Here, we show the current population status of the red‐necked wallaby (Notamacropus rufogriseus) in Britain based on records from an eleven‐year period (2008–2018). Records were obtained from Local Environmental Records Centres (LERCs), the National Biodiversity Network (NBN), and popular media. All records were mapped and compared to a historical distribution map (1940–2007), derived from published data. A total of 95 confirmed wallaby sightings were recorded between 2008 and 2018, of which 64 came from media sources, 18 from Local Environmental Records Centres (LERCs), seven from the National Biodiversity Network (NBN), and six from the published literature (Yalden, Br. Wildl., 24, 2013, 169). The greatest density of wallaby sightings was in southern England, with the Chiltern Hills Area of Outstanding Natural Beauty a particular hot spot (n = 11). More sightings were recorded in August than in any other month. Much of the species’ ecology and responses to British biota and anthropogenic pressures are unknown, and therefore, further research is warranted. The methods used here are widely applicable to other non‐native species, particularly those that the public are more likely to report and could be an important supplement to existing studies of conservation and management relevance.