bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of tumor immune microenvironment via microRNA‐1 after epidermal growth factor receptor‐tyrosine kinase inhibitor resistance acquirement in lung adenocarcinoma
Authors: Kawana Sachiko , Saito Ryoko , Miki Yasuhiro , Kimura Yuichiro , Abe Jiro , Sato Ikuro , Endo Mareyuki , Sugawara Shunichi , Sasano Hironobu 
Published: December 2020

AbstractImmunotherapy is considered one of the most important therapeutic strategies for patients with lung adenocarcinoma after the development of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) resistance. However, useful predictors of immunotherapy for these patients has not been examined well, although the status of the tumor immune microenvironment (TIME), including programmed death‐ligand 1 expression and lymphocyte infiltration, has been generally known to provide predictive markers for the efficacy of immunotherapy. This study aimed to clarify novel predictors of immunotherapy following EGFR‐TKI resistance in lung adenocarcinoma, especially regarding micro RNA (miRNA). We evaluated the correlation between EGFR‐TKI resistance and lymphocyte infiltration, before and after acquiring EGFR‐TKI resistance, in 21 cases of lung adenocarcinoma, and further explored this by in vitro studies, using miRNA PCR arrays. Subsequently, we transfected miRNA‐1 (miR‐1), the most variable miRNA in this array, into three kinds of lung cancer cells, and examined the effects of miR‐1 on EGFR‐TKI sensitivity, cytokine expression and lymphocyte migration. Histopathological examination demonstrated that infiltration levels of CD8‐positive T cells were significantly decreased after development of EGFR‐TKI resistance. In vitro studies revealed that miR‐1 significantly inhibited EGFR‐TKI effect and induction of cytokines, such as C‐C motif chemokine ligand 5 and C‐X‐C motif chemokine ligand 10, causing inhibition of monocyte migration. These results indicate that the upregulated miR‐1 might suppress the TIME, following development of EGFR‐TKI resistance. Therefore, miR‐1 could be a clinically useful marker to predict therapeutic efficacy of immunotherapy in lung adenocarcinoma patients with EGFR‐TKI resistance.
Evaluation of a framework for safe and appropriate prescribing of psychoactive medications in a UK prison
Authors: Bebbington Emily , Lawson Justin , Nafees Sadia , Robinson Catherine , Poole Rob 
Published: December 2020

AbstractBackgroundThe widespread use of drugs in prisons leads to avoidable deaths, poorer health and a poor living environment. The contribution of psychoactive prescription drugs to this problem has received little attention in prison policy or at individual prescriber level.AimsTo determine the extent of unsafe and inappropriate prescribing of psychoactive medications in one UK prison using a newly developed medicines optimisation framework.MethodA medicines optimisation framework was developed based on principles of good prescribing. It was initiated on the opening of a new prison—HMP Berwyn—in February 2017. During the study period, all prisoners at HMP Berwyn were transferred from other prisons. The safety and appropriateness of psychoactive medications were evaluated de novo on reception at HMP Berwyn and during follow up, using the medicines optimisation framework.ResultsAbout 1941 sentenced men arrived at HMP Berwyn between February 2017 and November 2018. Nearly one‐third (634, 33%) were on a prescribed psychoactive medication. Seventy‐five percent of these (474/634) required a prescription change due to appropriateness or safety concerns. Nearly half (295, 46.5%) received changes at reception despite having already undergone medicines reconciliation at their previous prison. Forty‐three percent (275/634) received changes at follow up, most commonly those who had no prior risks identified at reception.ConclusionsInappropriate and unsafe prescribing of psychoactive medications is occurring in prisons despite mandatory medication reviews. Ongoing monitoring is required to reduce the risk from these medications. A medicines optimisation framework such as this could be adopted across other prisons, worldwide, to help contribute to risk reduction from drug use in prisons. Appropriately modified, a similar framework might help reduce inappropriate and harmful prescribing in hospitals and in the community.
The improvement of the functional properties of a chickpea protein isolate through proteolysis with three proteases
Authors: Goertzen Alexandre D. , Nickerson Michael T. , Tanaka Takuji 
Published: December 2020

AbstractBackground and objectivesEnzymatic hydrolysis has previously been shown to have beneficial influences on the protein functionality of pulse protein isolates. To apply and optimize these benefits in chickpeas, a chickpea protein isolate (CPI) was hydrolyzed with three different proteases (trypsin, pepsin, and papain), to three different degrees of hydrolysis (DH): 5%, 10%, and 15%. Changes to zeta potential, hydrophobicity, water and oil holding capacity (WHC and OHC), as well as solubility, emulsifying, and foaming properties at pH 4.0, 7.0, and 10.0 of the various hydrolysates were then quantified and compared with one another in order to determine optimal hydrolytic conditions.FindingsIncreasing length of enzymatic treatments led to a gradual increase in zeta potential, and a rise in protein hydrophobicity. The solubility of trypsin and papain hydrolyzed CPI proteins increased at pH 10.0, while minor decreases in solubility were noted at pH 7.0. Increasing length of pepsin and papain treatment was noted to improve the water holding capacity (WHC), whereas hydrolysis with all three enzymes led to decreases in oil holding capacity (OHC). The emulsifying activity index (EAI) of the CPI increased following hydrolysis with all enzymes at pH 4.0 and 10.0, while at pH 7.0 no changes were observed. The emulsifying stability index (ESI) of the CPI increased following trypsin treatment at pH 4.0; at pH 10.0 emulsions appeared stable, exhibiting no separation over a 30‐min period. Foaming capacity (FC) increased following enzyme treatments at pH 4.0, pH 7.0, and more dramatically at pH 10.0. Foaming stability (FS) worsened at pH 10.0 following higher levels of trypsin hydrolysis (DH > 10%).ConclusionsApproximately 15% hydrolysis with papain was shown as the best conditions to augment the emulsifying, foaming and water holding properties of a CPI material, potentially allowing for the generation of specialized chickpea protein ingredients.Significance and noveltyA total of nine distinct CPI hydrolysates were generated and compared with one another to determine optimal hydrolytic conditions with respect to the functional properties of the CPI.
Severe Graves' disease‐associated orbitopathy: A rare case of frontal bone hemangioma
Authors: Alamri Ahmad , Pauchet Daphné , Balaton André , Oriez Constance , Dupuy Olivier , Ben Hamou Adrien 
Published: December 2020

AbstractGraves' orbitopathy might be severe, requiring treatment with high‐dose glucocorticoids. A lytic bone lesion, malignant lesions, and diseases resulting from bone remodeling processes (eg, Paget's disease) must be excluded by markers and imagery. Outcomes of high‐dose glucocorticoids and thyrotoxicosis must be screened and prevented.
XAD Resins for Increased Rebeccamycin Productivity in Cultivations of Lentzea aerocolonigenes
Authors: Schrinner Kathrin , Althof Kristina , Ebersbach Anna Theresia , Grosch Jan‐Hendrik , Krull Rainer 
Published: December 2020

AbstractLentzea aerocolonigenes produces the antitumor antibiotic rebeccamycin. For a medical application maximized titers and appropriate downstream processing are necessary. The addition of the adsorbents XAD 4, XAD 17 HP, and XAD 16 N was investigated for increased productivity and in situ product recovery. An increase in product titer was observed for XAD 7 HP and XAD 16 N. A combination of these particles with glass beads led to a further increase. Moreover, rebeccamycin can be adsorbed to these particles which facilitate the extraction since the liquid phase can be dispensed with.
The reaction between iodide and iodate ions – a long lasting kinetic problem
Authors: Heinzerling Peter , Schrader Frank 
Published: December 2020

AbstractZu den bekanntesten kinetisch untersuchten Reaktionen zählt die Reaktion zwischen Bromid und Bromat in saurer Lösung. Aufgrund der CMR‐Eigenschaften von Kaliumbromat gilt ein weitgehendes Verwendungsverbot in Schulen, so dass diese Reaktion im Unterricht nicht mehr experimentell untersucht werden darf. Hier wird als Alternative die Reaktion zwischen Iodid und Iodat in saurer Lösung vorgestellt. Es ergibt sich unter bestimmten Reaktionsbedingungen ein pentamolekulares Geschwindigkeitsgesetz.
Identification of Novel Fragments Binding to the PDZ1‐2 Domain of PSD‐95
Authors: Zang Jie , Ye Fei , Solbak Sara M. Ø. , Høj Lars J. , Zhang Mingjie , Bach Anders 
Published: December 2020

AbstractInhibition of PSD‐95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide‐based compounds that target the PDZ domains of PSD‐95. In contrast, developing potent and drug‐like small molecules against the PSD‐95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD‐95 PDZ1‐2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter‐test, and found four promising fragments. Three ligand efficient fragments were shown by 1H,15N HSQC NMR to bind in the small hydrophobic P0 pockets of PDZ1‐2, and one of them underwent structure‐activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1‐2 of PSD‐95 and disclose novel fragments that can serve as starting points for optimization towards small‐molecule PDZ domain inhibitors.
Design and Synthesis of Mucin‐Inspired Glycopolymers
Authors: Kwan Chak‐Shing , Cerullo Antonio R. , Braunschweig Adam B. 
Published: December 2020

AbstractMucins are bottlebrush biopolymers that are glycoproteins on the surfaces of cells and as hydrogels secreted inside and outside the body. Mucin function in biology includes cell‐cell recognition, signaling, protection, adhesion, and lubrication. Because of their attractive and diverse properties, mucins have recently become the focus of synthetic efforts by researchers who hope to understand and emulate these biomaterials. This review is focused on the development of methodologies for preparing mucin‐inspired synthetic oligomers and glycopolymers, including solid‐phase synthesis, polymerization of glycosylated monomers, and post‐polymerization grafting of glycans to polymer chains. How these synthetic mucins have been used in health applications is discussed. Natural mucins are formed from a conserved set of monomers that are combined into chains of different sequences and lengths to achieve materials with widely diverse properties. Adopting this design paradigm from natural mucins could lead to next‐generation bioinspired synthetic materials.
Enzyme‐free Recycling Amplification‐based Sensitive Electrochemical Thrombin Aptasensor
Authors: Zhang Xiuxiu , Liao Fusheng , Wang Mei , Zhang Jie , Xu Binxiang , Zhang Ling , Xiong Jun , Xiong Wei 
Published: December 2020

AbstractIn this work, an enzyme‐free recycling amplification‐based sensitive electrochemical thrombin aptasensor using catalytic hairpin assembly (CHA) and bisferrocene was proposed for electrochemical beacon. Thrombin triggered the CHA reaction that in turn formed a number of double‐stranded complexes,which are fixed on the surface of the gold electrode through potential‐assisted Au−S deposition, and a large number of labeled bisferrocene are placed close to the gold electrode to generate electrochemical signal. The linear range of the electrochemical sensor was 0.25 pM‐2.5 nM for thrombin with detection limit of 0.18 pM. This sensor can be employed to monitor the thrombin in human serum samples.
Modified class of explicit and enhanced stability region schemes: Application to mixed convection flow in a square cavity with a convective wall
Authors: Nawaz Yasir , Arif Muhammad Shoaib 
Published: December 2020

AbstractA modification of Adams–Bashforth methods is given to construct time discretization schemes for partial differential equations. The second‐order modified method is shown to have a larger stability region than second‐order standard Adams–Bashforth for the two‐dimensional heat equation. Later the scheme is applied on considered flow problem in a square cavity. The flow problem is a modified mathematical model of the heat and mass transfer of mixed convection flow in a square cavity with effects of the inclined magnetic field and thermal radiations. In addition to this, another feature of the present contribution is to apply the coupling approach for employing a mixture of stable and unstable schemes. This coupling approach is based upon the difference quotient that has been used in the literature to construct flux limiters for reducing oscillations in the discontinuous solutions of hyperbolic conservation laws. Since proposed scheme produces oscillation in the beginning and then diverges for the chosen diffusion number that falls in the unstable region, so these oscillations, due to instability, is reduced by coupling it with the scheme that can produce the convergent solution. The convergence of the proposed scheme for the considered modified nondimensional mathematical model of mixed convection flow is also given. The improvement is shown in graphs when proposed second order in time scheme is compared with the standard second order in time Adams–Bashforth method. Also, the mixture of first‐order and unconditionally unstable Richardson's schemes is applied, and the solution is obtained, and some plots are provided.
Characterization of TERT and BRAF copy number variation in papillary thyroid carcinoma: An analysis of the cancer genome atlas study
Authors: McKelvey Brittany A. , Zeiger Martha A. , Umbricht Christopher B. 
Published: December 2020

AbstractAlterations in the genome, including mutations and copy number variation (CNV), can drive cancer progression. The Cancer Genome Atlas (TCGA) project studying papillary thyroid cancer (PTC) identified a number of recurrent arm‐level copy number amplifications, some spanning genes that are also commonly mutated in thyroid cancer. Herein, we focus on the role of TERT and BRAF CNV in PTC, including its relation to mutation status, gene expression, and clinicopathological characteristics. Utilizing TCGA CNV data, we identified focal amplifications and deletions involving the TERT and BRAF loci. TERT amplifications are more frequent in later stage thyroid tumors; in contrast, BRAF amplifications are not associated with stage. Furthermore, TERT amplifications are more frequently found in tumors also harboring TERT mutations, the combination further increasing TERT expression. Conversely, BRAF amplifications are more frequently found in BRAF wildtype tumors, and are more common in the follicular subtype of PTC as well as classic PTCs associated with a high follicular component and a RAS‐like expression profile (assessed by the BRAF/RAS score). This is the first study to examine the TCGA thyroid dataset for gene‐level CNV of TERT and BRAF, and their relationship with mutation status, tumor type and tumor stage. Assessing the differences in patterns of TERT and BRAF amplifications in the context of the mutation status of these genes may provide insight into the differing roles CNV can play depending on tumor type, and may lead to a better understanding of cancer drivers in thyroid cancer.
Higher order chemical process with heat transport of magnetized cross nanofluid over wedge geometry
Authors: Shah Syed Z. H. , Wahab Hafiz A. , Ayub Assad , Sabir Zulqurnain , haider Ali , Shah Syed L. 
Published: December 2020

AbstractHeat transport keeps vital impact in field of engineering like heat spacing, air conditioning, refrigeration, and in chemical processing, such as heating of base and final products, heat recovery, tempering of containers, autoclaves, and reactors. This manuscript reveals theoretical and an experimental finding related for heat transport of unsteady cross nanofluid and chemical process with inclined magnetic field over the wedge. Heat transport is scrutinized with the existence of nonuniform heat sink source and radiation. Furthermore, mass transfer is studied with higher order chemical process, thermophoresis, and Brownian motion. Mathematical system produces nonlinear partial differential equations (PDEs) of time‐dependent velocity, energy, and concentration. Moreover, these PDEs changed into the system of nonlinear ordinary differential equations (ODEs). The obtained ODEs are passed out through shooting technique to convert the boundary value problem into initial value problem and further bvp4c took them for numerical solution. Bvp4c is MATLAB procedure, which is most convergent for numerical solution of ODEs based on RK‐45 procedure. Many applicable parameters are inspected graphically and in tabular form. Numerical outcomes related to physical quantities are hashed out in tabular form. Chemical process boosts the heat and mass transport. Higher radiation responses higher temperature and inclined magnetic strength reduces the velocity of cross nanofluid.
Improved visible‐light photocatalytic activities of carboxylate functionalized polystyrene@Fe3O4 nanocomposite and its mechanism insight
Authors: Zarshad Nighat , Khan Iltaf , Rahman Anis Ur , Ali Asad , Zaman Saeed , Khan Shoaib , Yasmeen Humaira , Qadar Naveed , Qi Kezhen , Ni Henmei 
Published: December 2020

AbstractHerein, we report a unique approach to synthesize dimpled shape carboxylate functionalized polystyrene (C‐PS), which were subsequently coated with Fe3O4 nanoparticles in situ by co‐precipitation method. The magnetization of C‐PS@Fe3O4 nanocomposite has been verified through vibrating sample magnetometer (VSM) measurements. The amount optimized carboxylate functionalized magnetic polystyrene (C‐PS@Fe3O4) exhibits 5.2 and 2.2‐times enhancement in visible‐light photocatalytic activities for 2,4‐dichlorophenol degradation compared with that of pristine PS and C‐PS. Based on various electro‐analytical techniques like surface photovoltage spectroscopy, temperature‐programmed desorption, Uv‐DRS, Scanning electron microscopy, transmission electron microscopy and VSM confirming magnetic nature of C‐PS@Fe3O4. Our results suggest that the improvement in visible light activities of C‐PS@Fe3O4 are comprehensively assigned to the large and active surface area due to charge separation, catalytic functions, and magnetic nature induced by Fe3O4 nanoparticles. Finally, this work will provide new strategy to synthesize visible light active nano photocatalysts with controllable shape, which for efficient environmental remediation.
HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3‐mediated m6A modification of HIF‐1α
Authors: Yang Nanmu , Wang Tao , Li Qingjun , Han Feng , Wang Zhengzheng , Zhu Ruili , Zhou Jinxue 
Published: December 2020

AbstractCancer cells sustain high levels of glycolysis and glutaminolysis via reprogramming of intracellular metabolism, which represents a driver of hepatocellular carcinoma (HCC) progression. Understanding the mechanisms of cell metabolic reprogramming may present a new basis for liver cancer treatment. Herein, we collected HCC tissues and noncancerous liver tissues and found hepatitis B virus X‐interacting protein (HBXIP) was found to be upregulated in HCC tissues and associated with poor prognosis. The N6‐methyladenosine (m6A) level of hypoxia‐inducible factor‐1α (HIF‐1α) in HCC cells was evaluated after the intervention of METTL3. The possible m6A site of HIF‐1α was queried and the binding relationship between METTL3 and HIF‐1α was verified. The interference of HBXIP suppressed HCC malignant behaviors and inhibited the Warburg effect in HCC cells. METTL3 was upregulated in HCC tissues and positively regulated by HBXIP. Overexpression of METTL3 restored cell metabolic reprogramming in HCC cells with partial loss of HBXIP. HBXIP mediated METTL3 to promote the metabolic reprogramming and malignant biological behaviors of HCC cells. The levels of total m6A in HCC cells and m6A in HIF‐1α were increased. METTL3 had a binding relationship with HIF‐1α and mediated the m6A modification of HIF‐1α. In conclusion, HBXIP drives metabolic reprogramming in HCC cells via METTL3‐mediated m6A modification of HIF‐1α.
Temperature‐mediated trade‐off between development and performance in larval wood frogs (Rana sylvatica)
Authors: Gahm Kaija , Arietta A. Z. Andis , Skelly David K. 
Published: December 2020

AbstractCountergradient variation has been detected in diverse taxa. In a common manifestation, individuals from colder environments develop faster than conspecifics from warmer environments when placed in a common garden. Where such a pattern exists, it implies a trade‐off: Individuals from warmer environments have intrinsic rates of development lower than those demonstrated by other individuals of the same species. We explored a trade‐off between development rate and locomotor performance in the wood frog (Rana sylvatica), an amphibian for which countergradient variation has been well documented. We reared wood frogs from 10 populations under two temperature regimes, bracketing the temperatures observed in local natural ponds. Individuals reared under warmer conditions developed more rapidly but exhibited burst speeds 20% lower than individuals reared under colder conditions. The slope of the reaction norm was consistent across the 10 populations and thus, we found no evidence of countergradient variation in performance. Burst speed assays of wild‐caught tadpoles from the same populations showed a similar but nonsignificant trend, with greater variability among ponds. Overall, our findings support the existence of a development–performance trade‐off that may be of broad importance and which may help explain the widespread occurrence of countergradient variation.