bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of drugs affecting hypertension in bevacizumab‐treated patients and examination of the impact on the therapeutic effect
Authors: Yagi Kenta , Mitstui Marin , Zamami Yoshito , Niimura Takahiro , Izawa‐Ishizawa Yuki , Goda Mitsuhiro , Chuma Masayuki , Fukunaga Kimiko , Shibata Takahiro , Ishida Shunsuke , Sakurada Takumi , Okada Naoto , Hamano Hirofumi , Horinouchi Yuya , Ikeda Yasumasa , Yanagawa Hiroaki , Ishizawa Keisuke 
Published: November 2020

AbstractBackgroundIn patients treated with bevacizumab, hypertension may be a biomarker of therapeutic efficacy. However, it is not clear whether drugs that control blood pressure influence bevacizumab's efficacy. In this study, we investigated drugs that may affect hypertension in bevacizumab‐treated patients and examined the impact on the therapeutic effect.Patients and methodsWe analyzed 3,724,555 reports from the third quarter of 2010 to the second quarter of 2015. All data were obtained from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) analysis. In this retrospective cohort study, we investigated a total of 58 patients diagnosed with colorectal cancer and treated for the first time with bevacizumab containing XELOX or mFOLFOX6 at The University of Tokushima Hospital between January 2010 and December 2015. The effect of the treatment was evaluated according to Response Evaluation Criteria in Solid Tumors version 1.0. Thereafter, the effect was confirmed using Gene Expression Omnibus (GEO) and cultured cells.ResultsThere are few reports in FAERS of hypertension in patients treated with omeprazole on bevacizumab. Based on the chart review, patients who used proton pump inhibitors (PPI) had a lower response to treatment than those who did not (response rate: 25% vs 50%). Furthermore, experiments on GEO and cell lines suggested that induction of vascular endothelial growth factor (VEGF) gene expression by PPIs is the cause of the reduced therapeutic effect.ConclusionPPIs prevent hypertension in bevacizumab‐treated patients but may reduce bevacizumab's anti‐tumoral effects by inducing VEGF expression.
Design and in Vitro Characterization of Tricyclic Benzodiazepine Derivatives as Potent and Selective Antileukemic Agents
Authors: Mieczkowski Adam , Frączyk Tomasz , Psurski Mateusz , Wińska Patrycja , Siedlecki Paweł , Dziełak Monika , Trzybiński Damian , Wilczek Marcin , Bagiński Maciej , Bieszczad Bartosz , Woźniak Krzysztof 
Published: November 2020

AbstractCurrently available chemotherapeutic treatments for blood cancers (leukemia) usually have strong side effects. More selective, efficient, and less toxic anticancer agents are needed. We synthesized seven, new, optically pure (12aS)‐1,3,4,12a‐tetrahydropyrazino[2,1‐c][1,4],12(2H,11H)‐dione derivatives and examined their cytotoxicity towards eight cancer cell lines, including urinary bladder (TCC‐SUP, UM‐UC‐3, KU‐19‐9), colon (LoVo), and breast (MCF‐7, MDA‐MB‐231) cancer representatives, as well as two leukemic cell lines (MV‐4‐11, CCRF‐CEM) and normal murine fibroblasts (Balb/3T3) as reference cell line. Three of the seven newly‐obtained compounds ((12aS)‐8‐bromo‐2‐(3‐phenylbenzoyl)‐1,3,4,12a‐tetrahydropyrazino[2,1‐c][1,4],12(2H,11H)‐dione, (12aS)‐8,9‐dimethoxy‐2‐(4‐phenylbenzoyl)‐1,3,4,12a‐tetrahydropyrazino[2,1‐c][1,4],12(2H,11H)‐dione and (12aS)‐8‐nitro‐2‐(4‐phenylbenzoyl)‐1,3,4,12a‐tetrahydropyrazino[2,1‐c][1,4],12(2H,11H)‐dione, showed enhanced activity and selectivity toward the leukemic MV‐4‐11 cell lines when compared to our previously reported compounds, with IC50 values in the range of 2.9–5.6 μM. Additionally, (12aS)‐9‐nitro‐2‐(4‐phenylbenzoyl)‐1,3,4,12a‐tetrahydropyrazino[2,1‐c][1,4],12(2H,11H)‐dione exhibited a strong cytotoxic effect against the leukemic CCRF‐CEM (IC50=6.1 μM) and MV‐4‐11 (IC50=11.0 μM) cell lines, a moderate cytotoxic effect toward other tumor lines (IC50=31.8–55.0 μM) and very weak cytotoxic effect toward the Balb/3T3 reference cell lines. Selected compounds were further evaluated for their potential to induce apoptotic cell death in MV‐4‐11 cells by measuring caspase‐3 activity. We also established the crystal structure of three products and investigated the effect of 22 derivatives of 1,3,4,12a‐tetrahydropyrazino[2,1‐c][1,4],12(2H,11H)‐dione on the activity of the cancer‐associated enzyme autotaxin. All compounds proved to be weak inhibitors of autotaxin, although some (R) and (S) enantiomers had Ki values of 10–19 μM. The obtained results showed that the tested compounds exhibited a selective antileukemic effect, which appeared not to be related directly to autotaxin. Molecular targets responsible for this effect remain to be identified. The newly obtained compounds can be used in the search for new, selective anticancer therapies.
A systematic review and meta‐analysis of impact of baseline thrombocytopenia on cardiovascular outcomes and mortality in patients undergoing percutaneous coronary intervention
Authors: Ahsan Muhammad J. , Lateef Noman , Latif Azka , Malik Saad U. , Batool Syeda S. , Fazeel Hafiz M. , Ahsan Mohammad Z. , Faizi Zaheer , Thandra Abhishek , Mirza Mohsin , Kabach Amjad , Core Michael Del 
Published: November 2020

AbstractBackgroundThrombocytopenia (TP) is associated with higher incidence of bleeding in the setting of percutaneous coronary intervention (PCI) leading to increased morbidity and mortality. Herein, we report a meta‐analysis evaluating the effects of baseline thrombocytopenia (bTP) on cardiovascular outcomes in patients undergoing PCI.MethodsLiterature search was performed using PubMed, Embase, Cochrane library and clinicaltrials.gov from inception till October 2019. Patients were divided into two groups: Patients with (a) no Thrombocytopenia (nTP) (b) bTP before PCI. Primary endpoints were in‐hospital, and all‐cause mortality rates at the longest follow‐up. The main summary estimate was random effects risk ratio (RR) with 95% confidence intervals (CIs).ResultsA total of 6,51,543 patients from 10 retrospective studies were included. There was increased in‐hospital all‐cause mortality (RR 2.58 [1.7–3.8], p < .001) and bleeding (RR 2.37 [1.41–3.98], p < .005), in the bTP group compared to the nTP group. There was no difference for in‐hopsital major adverse cardiovascular outcomes (MACE) (RR 1.38 [0.94–2.0], p < .10), post‐PCI MI (RR 1.17 [0.9–1.5], p = .19) and TVR (RR 1.65 [0.8–3.6], p = .21), respectively. Outcomes at longest follow‐up showed increased incidence of all‐cause mortality (RR 1.86 [1.2–2.9], p < .006) and bleeding (RR 1.72 [1.1–2.9], p = .04) in bTP group, while there was no significant difference for post‐PCI MI (RR 1.07 [0.91–1.3], p = .42), MACE (RR 1.86 [0.69–1.8], p = .68) and TVR (RR 1.1 [0.9–1.2], p = .93) between both groups.ConclusionsbTP in patients undergoing PCI is associated with increased mortality and predicts risk of bleeding.
Adsorption of Iodide and Bromide on Au(111) Electrodes from Aprotic Electrolytes: Role of the Solvent
Authors: Shatla Ahmed S. , Bawol Pawel P. , Baltruschat Helmut 
Published: November 2020

AbstractThe adsorption of iodide and bromide ions on Au(111) single‐crystal electrodes in three organic solvents [propylene carbonate (PC), diglyme (DG), and dimethyl sulfoxide (DMSO)] was studied by differential capacity measurements, cyclic voltammetry (CV), X‐ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). The anion adsorption charge in DMSO is approximately half as large as in propylene carbonate and that in water. Quantification of the adsorbed iodide amount from XPS spectra confirms the coverage estimated from the adsorption charge in CVs. As expected, the rate of anion adsorption on Au(111) is higher for I− than for Br− due to better solvation of the latter. The extent of anion adsorption on Au(111) electrode decreases and the corresponding adsorption rate decreases in the solvent order H2O>PC>DG>DMSO. Since the donor number (DN) of the solvent increases in the same order (PC<DG<DMSO), we assume that it plays a decisive role since it determines the chemical interaction of the solvent with the metal surface. Moreover, the adsorption rate of iodide and the extent of its adsorption is increased with increasing water content in PC and DMSO. This effect, and the much higher adsorption rate in water is explained by the closer approach of the solvated halogen ion to the surface and the resulting stronger interaction of the transition state with the electrode.
A Domino Fusion of an Organic Ligand Depended on Metal‐Induced and Oxygen Insertion, Unraveled by Crystallography, Mass Spectrometry, and DFT Calculations
Authors: Chen Jin‐Ming , Peng Liang , Zhou Fu‐Fang , Liu Bin , Hou Cheng , Li Jia‐Wei , Huang Zhou , Kurmoo Mohamedally , Zeng Ming‐Hua 
Published: November 2020

AbstractHerein, the reaction of (1‐methyl‐1 H‐benzo[d]imidazol‐2‐yl)methanamine (L1) with Co(H2O)6Cl2, in CH3CN at 120 °C, leading to the 2,3,5,6‐tetrakis(1‐methyl‐1 H‐benzo[d]imidazol‐2‐yl)pyrazine (3), isolated as a dimeric cluster {[CoII2(3)Cl4]⋅2 CH3CN} (2), is reported. When O2 and H2O are present, (1‐methyl‐1 H‐benzo[d]imidazole‐2‐carbonyl)amide (HL1′) is first formed and crystallized as [CoIII(L1)2(L1′)]Cl2⋅2 H2O (4) before fusion of HL1′ with L1, giving 1‐methyl‐N‐(1‐methyl‐1 H‐benzo[d]imidazol‐2‐carbonyl)‐1 H‐benzo[d]imidazol‐2‐carboxamide (HL2′′) forming a one‐dimensional (1D) chain of [CoII3(L2′′)2Cl4]n (5). The combination of crystallography and mass spectrometry (ESI‐MS) of isolated crystals and the solutions taken from the reaction as a function time reveal seven intermediate steps leading to 2, but six steps for 5, for which a different sequence takes place. Control and isotope labeling experiments confirm the two carbonyl oxygen atoms in 5 originate from both air and water. The dependence on the metals, compared with FeCl3⋅6 H2O leading to a stable triheteroarylmethyl radical, is quite astounding, which could be attributed to the different oxidation states of the metals and coordination modes confirmed by DFT calculations. This metal and valence dependent process is a very useful way for selectively obtaining these large molecules, which are unachievable by common organic synthesis.
Replacing the Rhamnose‐Xylose Moiety of QS‐21 with Simpler Terminal Disaccharide Units Attenuates Adjuvant Activity in Truncated Saponin Variants
Authors: Fuentes Roberto , Ruiz‐de‐Angulo Ane , Sacristán Nagore , Navo Claudio Daniel , Jiménez‐Osés Gonzalo , Anguita Juan , Fernández‐Tejada Alberto 
Published: November 2020

AbstractAdjuvants are key immunostimulatory components in vaccine formulations, which improve the immune response to the co‐administered antigen. The saponin natural product QS‐21 is one of the most promising immunoadjuvants in the development of vaccines against cancer and infectious diseases but suffers from limitations that have hampered its widespread human use. Previous structure–activity relationship studies have identified simplified saponin variants with truncated carbohydrate chains, but have not focused on the influence of the linear oligosaccharide domain of QS‐21 in adjuvant activity. Herein, an expeditious 15‐step synthesis of new linear trisaccharide variants of simplified QS‐21‐derived adjuvants is reported, in which the complex terminal xylose‐rhamnose moiety has been replaced with commercially available, simpler lactose and cellobiose disaccharides in a β‐anomeric configuration. In vivo immunological evaluation of the synthetic saponins showed attenuated antibody responses, highlighting the negative impact of such carbohydrate modifications on adjuvant activity, which could be associated with higher saponin conformational flexibility.
Understanding the C−F Bond Activation Mediated by Frustrated Lewis Pairs: Crucial Role of Non‐covalent Interactions
Authors: Cabrera‐Trujillo Jorge Juan , Fernández Israel 
Published: November 2020

AbstractThe activation of a single C−F bond in di‐ and trifluoromethyl groups by frustrated Lewis pairs (FLPs) has been computationally explored by means of Density Functional Theory calculations. It is found that in this activation reaction the FLP partners exhibit a peculiar cooperative action, which is markedly different from related FLP‐mediated processes, and where non‐covalent interactions established between the Lewis base and the substrate play a decisive role. In addition, the process proceeds through the intermediacy of a hypervalent species featuring a pentacoordinate carbon atom, which is rare in the chemistry of FLPs. The physical factors controlling this process as well as the bonding situation of these hypervalent intermediates have been quantitatively analyzed in detail by using state‐of‐the‐art computational methods to not only rationalize the mechanism of the transformation but also to guide experimentalists towards the realization of these so far elusive hypervalent systems.
Interdisciplinary care of pediatric oncology patients in Central America and the Caribbean
Authors: Graetz Dylan E. , Chen Yichen , Devidas Meenakshi , Antillon‐Klussmann Federico , Fu Ligia , Quintero Karina , Fuentes‐Alabi Soad L. , Gassant Pascale Y. , Kaye Erica C. , Baker Justin N. , Rodriguez Galindo Carlos , Mack Jennifer W. 
Published: November 2020

BackgroundInterdisciplinary teamwork supports high‐quality cancer care and effective utilization of limited resources. This study purposed to examine the value, structure, process, and effectiveness of interdisciplinary care (IDC) among pediatric oncology providers in low‐income and middle‐income countries in Central America and the Caribbean.MethodsA cross‐sectional survey was disseminated to pediatric oncology providers at 5 centers participating in the Pediatric Hematology‐Oncology Association of Central America. The survey included previously validated items and novel questions assessing the value (importance), structure (multidisciplinary meeting attendance), process (team climate), and effectiveness (job satisfaction, quality of care and communication) of IDC.ResultsThe survey was completed by 174 providers, including 22 oncologists, 9 pathologists, 9 radiologists, 5 radiation oncologists, 12 surgeons, 35 subspecialists, 60 nurses, 20 psychosocial providers, and 2 other staff. Participants agreed that IDC benefits team members (95%) and patients (96%). IDC structure and processes varied across the region. Multidisciplinary meeting attendance differed by center (P = .005) and discipline (P < .0001). Participants who frequently attended multidisciplinary meetings reported a more positive team climate (P = .0003). Team climate was positively associated with job satisfaction (P < .001). In multivariable analyses, team climate was predictive of an improved perception of communication between professionals (P < .0001), with families (P < .0001), and with patients (P = .0005), as well as with quality of the care environment (P = .006) and overall care quality (P < .0001).ConclusionsNearly all surveyed participants valued IDC, and the structure and processes supporting IDC varied by center. Associations between a collaborative professional climate, job satisfaction, and the perception of quality care encourage continued investigation and prioritization of IDC in these settings.
Gait speed, survival, and recommended treatment intensity in older adults with blood cancer requiring treatment
Authors: Hantel Andrew , DuMontier Clark , Odejide Oreofe O. , Luskin Marlise R. , Sperling Adam S. , Hshieh Tammy , Chen Richard , Soiffer Robert , Driver Jane A. , Abel Gregory A. 
Published: November 2020

BackgroundBrief measures of physical function such as gait speed may be useful to optimize treatment intensity for older adults who have blood cancer; however, little is known about whether such assessments are already captured within oncologists' “gestalt” assessments.MethodsGait speed was assessed in 782 patients ≥75 years of age who had blood cancer, with results reported to providers after treatment decisions were made; 408 patients required treatment when different intensities were available per National Comprehensive Cancer Network (NCCN) guidelines. We performed structured abstractions of treatment intensity recommendations into standard intensity, reduced intensity, or supportive care, based on NCCN guidelines. We modeled gait speed and survival using Cox regression and performed ordinal logistic regression to assess predictors of NCCN‐based categorizations of oncologists' treatment intensity recommendations, including gait speed.ResultsThe median survival by gait speed category was 10.8 months (<0.4 m/s), 18.6 months (0.4‐0.6 m/s), 34.0 months (0.6‐0.8 m/s), and unreached (>0.8 m/s). Univariable hazard ratios (HRs) for death increased for each lower category compared with ≥0.8 m/s (0.6‐0.8 m/s: HR, 1.76; 0.4‐0.6 m/s: HR, 2.30; <0.4 m/s: HR, 3.31). Gait speed predicted survival in multivariable Cox regression (all P < .05). In multivariable models including age, sex, and Eastern Cooperative Oncology Group performance status, gait speed did not predict oncologists' recommended treatment intensity (all P > .05) and did not add to a base model predicting recommended treatment intensity.ConclusionIn older adults with blood cancer who presented for treatment, gait speed predicted survival but not treatment intensity recommendation. Incorporating gait speed into decision making may improve optimal treatment selection.
Enhancement of 1T‐MoS2 Superambient Temperature Stability and Hydrogen Evolution Performance by Intercalating a Phenanthroline Monolayer
Authors: Goloveshkin Alexander S. , Lenenko Natalia D. , Naumkin Alexander V. , Pereyaslavtsev Alexander Yu. , Grigorieva Anastasia V. , Shapovalov Aleksei V. , Talanova Valeria N. , Polezhaev Alexander V. , Zaikovskii Vladimir I. , Novikov Valentin V. , Korlyukov Alexander A. , Golub Alexandre S. 
Published: November 2020

AbstractMetastable modification of MoS2 (1T) is widely recognized as a hopeful non‐precious electrocatalyst in hydrogen production. This paper describes an approach to impart a superambient temperature stability to 1T‐MoS2 by incorporating it in 2D hybrid architecture with cationic monomolecular phenanthrolinium (PhenH+) hydrate layers. The atomic structure and bonding interactions of the assembled architecture revealed by PXRD, TEM, XPS, Raman and UV‐Vis spectroscopy data coupled with DFT calculations and quantum theory of atoms in molecules (QTAIM) analysis suggest that the 1T‐MoS2 sheets are involved in strong bonding with the PhenH‐H2O layers. This results in a highly stable layered system, which is kept intact in 0.5 M sulfuric acid electrolyte and tolerates superambient temperature heating. As compared with pure 1T‐MoS2, the compound with a phenanthroline interlayer provides greater activity and better current‐voltage efficiency in electrocatalytic hydrogen evolution after heating treatment owing to stabilization of the 1T phase. The obtained results could be useful for the design of novel electrocatalytic devices exploiting 1T‐MoS2 modification.
A Guide to Fluorescence Lifetime Microscopy and Förster's Resonance Energy Transfer in Neuroscience
Authors: Liput Daniel J. , Nguyen Tuan A. , Augustin Shana M. , Lee Jeong Oen , Vogel Steven S. 
Published: November 2020

AbstractFluorescence lifetime microscopy (FLIM) and Förster's resonance energy transfer (FRET) are advanced optical tools that neuroscientists can employ to interrogate the structure and function of complex biological systems in vitro and in vivo using light. In neurobiology they are primarily used to study protein‐protein interactions, to study conformational changes in protein complexes, and to monitor genetically encoded FRET‐based biosensors. These methods are ideally suited to optically monitor changes in neurons that are triggered optogenetically. Utilization of this technique by neuroscientists has been limited, since a broad understanding of FLIM and FRET requires familiarity with the interactions of light and matter on a quantum mechanical level, and because the ultra‐fast instrumentation used to measure fluorescent lifetimes and resonance energy transfer are more at home in a physics lab than in a biology lab. In this overview, we aim to help neuroscientists overcome these obstacles and thus feel more comfortable with the FLIM‐FRET method. Our goal is to aid researchers in the neuroscience community to achieve a better understanding of the fundamentals of FLIM‐FRET and encourage them to fully leverage its powerful ability as a research tool. Published 2020. U.S. Government.
Grass Gazers: Using citizen science as a tool to facilitate practical and online science learning for secondary school students during the COVID‐19 lockdown
Authors: Van Haeften Shanice , Milic Andelija , Addison‐Smith Beth , Butcher Christopher , Davies Janet Mary 
Published: November 2020

AbstractThe coronavirus disease of 2019 (COVID‐19) pandemic has impacted educational systems worldwide during 2020, including primary and secondary schooling. To enable students of a local secondary school in Brisbane, Queensland, to continue with their practical agricultural science learning and facilitate online learning, a “Grass Gazers” citizen science scoping project was designed and rapidly implemented as a collaboration between the school and a multidisciplinary university research group focused on pollen allergy. Here, we reflect on the process of developing and implementing this project from the perspective of the school and the university. A learning package including modules on pollen identification, tracking grass species, measuring field greenness, using a citizen science data entry platform, forensic palynology, as well as video guides, risk assessment and feedback forms were generated. Junior agriculture science students participated in the learning via online lessons and independent data collection in their own local neighborhood and/or school grounds situated within urban environments. The university research group and school coordinator, operating in their own distributed work environments, had to develop, source, adopt, and/or adapt material rapidly to meet the unique requirements of the project. The experience allowed two‐way knowledge exchange between the secondary and tertiary education sectors. Participating students were introduced to real‐world research and were able to engage in outdoor learning during a time when online, indoor, desk‐based learning dominated their studies. The unique context of restrictions imposed by the social isolation policies, as well as government Public Health and Department of Education directives, allowed the team to respond by adapting teaching and research activity to develop and trial learning modules and citizen science tools. The project provided a focus to motivate and connect teachers, academic staff, and school students during a difficult circumstance. Extension of this citizen project for the purposes of research and secondary school learning has the potential to offer ongoing benefits for grassland ecology data acquisition and student exposure to real‐world science.