bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation of a 16π‐Electrons 1,4‐Diphosphinine‐1,4‐diide with a Planar C4P2Ring
Authors: Rottschäfer Dennis , Neumann Beate , Stammler Hans‐Georg , Sergeieva Tetiana , Andrada Diego M. , Ghadwal Rajendra S. 
Published: October 2020

AbstractHerein, we report the first 1,4‐diphosphinine‐1,4‐diide compound [(ADCPh)P]2(5‐Ph) (ADCPh=PhC{(NDipp)C}2; Dipp=2,6‐iPr2C6H3) derived from an anionic dicarbene (ADCPh) as a red crystalline solid. Compound5‐Phcontaining a 16π‐electron planar fused‐tricyclic ring system was obtained by the 4e reduction of [(ADCPh)PCl2]2(4‐Ph) with Mg (or KC8) in a quantitative yield. Experimental and computational results imply that the central 8π‐electrons C4P2ring of5‐Ph, which is fused between two 6π‐electrons C3N2aromatic rings, is antiaromatic. Thus, each of the phosphorus atoms of5‐Phhas two electron‐lone‐pairs, one in a p‐type orbital is in conjugation with the C=C bonds of the C4P2ring, while the second resides in a σ‐symmetric orbital. This can be shown with the gold complex [(ADCPh)P(AuCl)2]2(6‐Ph) obtained by reacting5‐Phwith (Me2S)AuCl. A mixture of5‐Phand4‐Phundergoes comproportionation in the presence of MgCl2to form the intermediate oxidation state compound [(ADCAr)P]2(MgCl4) (7‐Ph), which is an aromatic species.
Synthesis of Morpholine‐Based Analogues of (−)‐Zampanolide and Their Biological Activity
Authors: Bold Christian Paul , Gut Melanie , Schürmann Jasmine , Lucena‐Agell Daniel , Gertsch Jürg , Díaz José Fernando , Altmann Karl‐Heinz 
Published: October 2020

AbstractWe describe the convergent synthesis of three prototypical examples of a new class of analogues of the complex, cytotoxic marine macrolide (−)‐zampanolide that incorporate an embedded N‐substituted morpholine moiety in place of the natural tetrahydropyran ring. The final construction of the macrolactone core was based on a high‐yielding intramolecular HWE olefination, while the hemiaminal‐linked side chain was elaborated through a stereoselective, BINAL‐H‐mediated addition of (Z,E)‐sorbamide to a macrocyclic aldehyde precursor. The synthesis of the common functionalized morpholine building block involved two consecutive epoxide openings with tosylamide and the product of the first opening reaction, respectively, as nucleophiles. Of the three morpholino‐zampanolides investigated, the N‐acetyl and the N‐benzoyl derivatives both exhibited nanomolar antiproliferative activity, thus being essentially equipotent with the natural product. In contrast, the activity of the N‐tosyl derivative was significantly reduced.
Strain Release Chemistry of Photogenerated Small‐Ring Intermediates
Authors: Luque Adriana , Paternoga Jan , Opatz Till 
Published: October 2020

AbstractPhotochemical processes, such as isomerizations and cycloadditions, have proven to be very useful in the construction of highly strained molecular frameworks. Photoinduced ring strain enables subsequent exergonic reactions which do not require the input of additional chemical energy and provides a variety of attractive synthetic options leading to complex structures. This review covers the progress achieved in the application of sequences combining excitation by ultraviolet light to form strained intermediates, which are further transformed to lower energy products in strain‐release reactions. As ring strain is considerable in small ring systems, photogenerated three‐ and four‐membered rings will be covered, mainly focusing on examples from 2000 to May 2020.
Efficacy and safety of dronedarone by atrial fibrillation history duration: Insights from theATHENAstudy
Authors: Blomström‐Lundqvist Carina , Marrouche Nassir , Connolly Stuart , Corp dit Genti Valérie , Wieloch Mattias , Koren Andrew , Hohnloser Stefan H. 
Published: October 2020

AbstractBackgroundAtrial fibrillation/atrial flutter (AF/AFL) burden increases with increasing duration of AF/AFL history.HypothesisOutcomes with dronedarone may also be impacted by duration of AF/AFL history.MethodsIn this post hoc analysis of ATHENA, efficacy and safety of dronedarone vs placebo were assessed in groups categorized by time from first known AF/AFL episode to randomization (ie, duration of AF/AFL history): <3 months (short), 3 to <24 months (intermediate), and ≥ 24 months (long).ResultsOf 2859 patients with data on duration of AF/AFL history, 45.3%, 29.6%, and 25.1% had short, intermediate, and long histories, respectively. Patients in the long history group had the highest prevalence of structural heart disease and were more likely to be in AF/AFL at baseline. Placebo‐treated patients in the long history group also had the highest incidence of AF/AFL recurrence and cardiovascular (CV) hospitalization during the study. The risk of first CV hospitalization/death from any cause was lower with dronedarone vs placebo in patients with short (hazard ratio, 0.79 [95% confidence interval: 0.65‐0.96]) and intermediate (0.72 [0.56‐0.92]) histories; a trend favoring dronedarone was also observed in patients with long history (0.84 [0.66‐1.07]). A similar pattern was observed for first AF/AFL recurrence. No new drug‐related safety issues were identified.ConclusionsPatients with long AF/AFL history had the highest burden of AF/AFL at baseline and during the study. Dronedarone significantly improved efficacy vs placebo in patients with short and intermediate AF/AFL histories. While exploratory, these results support the potential value in initiating rhythm control treatment early in patients with AF/AFL.
Chlorhexidine gluconate bathing in children with cancer or those undergoing hematopoietic stem cell transplantation: A double‐blinded randomized controlled trial from the Children's Oncology Group
Authors: Zerr Danielle M. , Milstone Aaron M. , Dvorak Christopher C. , Adler Amanda L. , Chen Lu , Villaluna Doojduen , Dang Ha , Qin Xuan , Addetia Amin , Yu Lolie C. , Conway Keller Mary , Esbenshade Adam J. , August Keith J. , Fisher Brian T. , Sung Lillian 
Published: October 2020

BackgroundTo the authors' knowledge, information regarding whether daily bathing with chlorhexidine gluconate (CHG) reduces central line–associated bloodstream infection (CLABSI) in pediatric oncology patients and those undergoing hematopoietic stem cell transplantation (HCT) is limited.MethodsIn the current multicenter, randomized, double‐blind, placebo‐controlled trial, patients aged ≥2 months and <22 years with cancer or those undergoing allogeneic HCT were randomized 1:1 to once‐daily bathing with 2% CHG‐impregnated cloths or control cloths for 90 days. The primary outcome was CLABSI. Secondary endpoints included total positive blood cultures, acquisition of resistant organisms, and acquisition of cutaneous staphylococcal isolates with an elevated CHG mean inhibitory concentration.ResultsThe study was stopped early because of poor accrual. Among the 177 enrolled patients, 174 were considered as evaluable (88 were randomized to the CHG group and 86 were randomized to the control group). The rate of CLABSI per 1000 central line days in the CHG group was 5.44 versus 3.10 in the control group (risk difference, 2.37; 95% confidence interval, 0.05‐4.69 [P = .049]). Post hoc conditional power analysis demonstrated a 0.2% chance that the results would have favored CHG had the study fully enrolled. The rate of total positive blood cultures did not differ between groups (risk difference, 2.37; 95% confidence interval, −0.41 to 5.14 [P = .078]). The number of patients demonstrating the new acquisition of resistant organisms did not differ between groups (P = .54). Patients in the CHG group were found to be more likely to acquire cutaneous staphylococcal isolates with an elevated CHG mean inhibitory concentration (P = .032).ConclusionsThe data from the current study do not support the use of routine CHG bathing in children with cancer or those undergoing allogeneic HCT.
Cell‐mediated and humoral adaptive immune responses to SARS‐CoV‐2 are lower in asymptomatic than symptomatic COVID‐19 patients
Authors: Mazzoni Alessio , Maggi Laura , Capone Manuela , Spinicci Michele , Salvati Lorenzo , Colao Maria Grazia , Vanni Anna , Kiros Seble Tekle , Mencarini Jessica , Zammarchi Lorenzo , Mantengoli Elisabetta , Menicacci Lorenzo , Caldini Eleonora , Romagnani Sergio , Liotta Francesco , Morettini Alessandro , Rossolini Gian Maria , Bartoloni Alessandro , Cosmi Lorenzo , Annunziato Francesco 
Published: October 2020

AbstractThe characterization of cell‐mediated and humoral adaptive immune responses to SARS‐CoV‐2 is fundamental to understand COVID‐19 progression and the development of immunological memory to the virus. In this study, we detected T‐cells reactive to SARS‐CoV‐2 proteins M, S, and N, as well as serum virus‐specific IgM, IgA, IgG, in nearly all SARS‐CoV‐2 infected individuals, but not in healthy donors. Virus‐reactive T cells exhibited signs of in vivo activation, as suggested by the surface expression of immune‐checkpoint molecules PD1 and TIGIT. Of note, we detected antigen‐specific adaptive immune response both in asymptomatic and symptomatic SARS‐CoV‐2 infected subjects. More importantly, symptomatic patients displayed a significantly higher magnitude of both cell‐mediated and humoral adaptive immune response to the virus, as compared to asymptomatic individuals. These findings suggest that an uncontrolled adaptive immune response contribute to the development of the life‐threatening inflammatory phase of the disease. Finally, this study might open the way to develop effective vaccination strategies.
Ionic Liquid and f‐MWCNTs Fabricated Glassy Carbon Electrode for Determination of Amygdalin in Apple Seeds
Authors: Chokkareddy Rajasekhar , Redhi Gan G 
Published: October 2020

AbstractThis work proposes a novel electrochemical sensor based on functionalised multiwalled carbon nanotubes (f‐MWCNTs), zinc oxide nanoparticles (ZnONPs), and (methyltrioctylammonium chloride ionic liquid (IL)) fabricated glassy carbon electrode (GCE), for the determination of amygdalin (AMY) in apple seeds. X‐ray diffraction (XRD), Brunauer‐Emmett‐Teller (BET), Fourier‐transform infrared spectroscopy (FT‐IR), Transmission electron microscopy (TEM), Thermogravimetric analysis (TGA) as well as electrochemical impedance spectroscopy (EIS) techniques were used to characterize the synthesized ZnONPs and its nanocomposite. EIS and differential Pulse Voltammetry (DPV) was utilized to investigate the electrochemical behavior of AMY on the IL‐ZnONPs‐f‐MWCNTs nanocomposite modified GCE. The linear range response is obtained from 0.012–6 μM for AMY determination under optimized experimental conditions, and the limit of detection (LOD) values were found to be 0.012 μM. The novel method developed was successfully used to determine AMY in spiked apple seed samples with satisfactory results.
Bifunctional Behavior of Pd/Ni Nanocatalysts on MOF‐Derived Carbons for Alkaline Water‐splitting
Authors: Ipadeola Adewale K. , Mwonga Patrick V. , Ray Sekar C. , Maphanga Rapela R. , Ozoemena Kenneth I. 
Published: October 2020

AbstractMetal‐organic framework derived carbon (MOFDC) serves as supporting platforms for PdNi catalyst (Pd/Ni/MOFDC) and acid‐treated nickel counterpart (Pd/AT‐Ni/MOFDC). The two Pd‐based electrocatalysts are tested for alkaline water‐splitting (i. e., hydrogen evolution (HER) and oxygen evolution reactions (OER)). The results reveal better HER and OER kinetics for Pd/Ni/MOFDC than Pd/AT‐Ni/MOFDC. DFT calculations show that the high performance of the Pd/Ni/MOFDC can be associated with its high conductivity toward adsorbed OH compared to the Pd/AT‐Ni/MOFDC counterpart. The superior overall water‐splitting of Pd/Ni/MOFDC describes the synergy between Ni/Ni(OH)2 interface and nanostructured Pd for possible future application in an electrolyzer.
Tall building performance‐based seismic design using SCEC broadband platform site‐specific ground motion simulations
Authors: Zhong Kuanshi , Lin Ting , Deierlein Gregory G. , Graves Robert W. , Silva Fabio , Luco Nicolas 
Published: October 2020

AbstractThe scarcity of strong ground motion records presents a challenge for making reliable performance assessments of tall buildings whose seismic design is controlled by large‐magnitude and close‐distance earthquakes. This challenge can be addressed using broadband ground‐motion simulation methods to generate records with site‐specific characteristics of large‐magnitude events. In this paper, simulated site‐specific earthquake seismograms, developed through a related project that was organized through the Southern California Earthquake Center (SCEC) Ground Motion Simulation Validation (GMSV) Technical Activity Group, are used for nonlinear response history analyses of two archetype tall buildings for sites in San Francisco, Los Angeles, and San Bernardino. The SCEC GMSV team created the seismograms using the Broadband Platform (BBP) simulations for five site‐specific earthquake scenarios. The two buildings are evaluated using nonlinear dynamic analyses under comparable record suites selected from the simulated BBP catalog and recorded motions from the NGA‐West database. The collapse risks and structural response demands (maximum story drift ratio, peak floor acceleration, and maximum story shear) under the BBP and NGA suites are compared. In general, this study finds that use of the BBP simulations resolves concerns about estimation biases in structural response analysis which are caused by ground motion scaling, unrealistic spectral shapes, and overconservative spectral variations. While there are remaining concerns that strong coherence in some kinematic fault rupture models may lead to an overestimation of velocity pulse effects in the BBP simulations, the simulations are shown to generally yield realistic pulse‐like features of near‐fault ground motion records.
Selection on a small genomic region underpins differentiation in multiple color traits between two warbler species
Authors: Wang Silu , Rohwer Sievert , de Zwaan Devin R. , Toews David P. L. , Lovette Irby J. , Mackenzie Jacqueline , Irwin Darren 
Published: October 2020

AbstractSpeciation is one of the most important processes in biology, yet the study of the genomic changes underlying this process is in its infancy. North American warbler species Setophaga townsendi and Setophaga occidentalis hybridize in a stable hybrid zone, following a period of geographic separation. Genomic differentiation accumulated during geographic isolation can be homogenized by introgression at secondary contact, whereas genetic regions that cause low hybrid fitness can be shielded from such introgression. Here, we examined the genomic underpinning of speciation by investigating (1) the genetic basis of divergent pigmentation traits between species, (2) variation in differentiation across the genome, and (3) the evidence for selection maintaining differentiation in the pigmentation genes. Using tens of thousands of single nucleotide polymorphisms (SNPs) genotyped in hundreds of individuals within and near the hybrid zone, genome-wide association mapping revealed a single SNP associated with cheek, crown, breast coloration, and flank streaking, reflecting pleiotropy (one gene affecting multiple traits) or close physical linkage of different genes affecting different traits. This SNP is within an intron of the RALY gene, hence we refer to it as the RALY SNP. We then examined between-species genomic differentiation, using both genotyping-by-sequencing and whole genome sequencing. We found that the RALY SNP is within one of the highest peaks of differentiation, which contains three genes known to influence pigmentation: ASIP, EIF2S2, and RALY (the ASIP-RALY gene block). Heterozygotes at this gene block are likely of reduced fitness, as the geographic cline of the RALY SNP has been narrow over two decades. Together, these results reflect at least one barrier to gene flow within this narrow (∼200 kb) genomic region that modulates plumage difference between species. Despite extensive gene flow between species across the genome, this study provides evidence that selection on a phenotype-associated genomic region maintains a stable species boundary.
Consequences of Perioperative Serotonin Reuptake Inhibitor Treatment During Hepatic Surgery
Authors: Starlinger Patrick , Pereyra David , Hackl Hubert , Ortmayr Gregor , Braunwarth Eva , Santol Jonas , Najarnia Sina , Driedger Michael R. , Gregory Lindsey , Alva‐Ruiz Roberto , Glasgow Amy , Assinger Alice , Nagorney David M. , Habermann Elizabeth B. , Staetttner Stefan , Cleary Sean P. , Smoot Rory L. , Gruenberger Thomas 
Published: October 2020

Background and Aims
Platelet‐stored serotonin critically affects liver regeneration in mice and humans. Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenalin reuptake inhibitors (SNRIs) reduce intraplatelet serotonin. As SSRIs/SNRIs are now one of the most commonly prescribed drugs in the United States and Europe and given serotonin’s impact on liver regeneration, we evaluated whether perioperative use of SSRIs/SNRIs affects outcome after hepatic resection.

Approach and Results
Consecutive patients undergoing hepatic resection (n = 754) were retrospectively included from prospectively maintained databases from two European institutions. Further, an independent cohort of 495 patients from the United States was assessed to validate our exploratory findings. Perioperative intake of SSRIs/SNRIs was recorded, and patients were followed up for postoperative liver dysfunction (LD), morbidity, and mortality. Perioperative intraplatelet serotonin levels were significantly decreased in patients receiving SSRI/SNRI treatment. Patients treated with SSRIs/SNRIs showed a higher incidence of morbidity, severe morbidity, LD, and LD requiring intervention. Associations were confirmed in the independent validation cohort. Combined cohorts documented a significant increase in deleterious postoperative outcome (morbidity odds ratio [OR], 1.56; 95% confidence interval [CI], 1.07‐2.31; severe morbidity OR, 1.86; 95% CI, 1.22‐2.79; LD OR, 1.96; 95% CI, 1.23‐3.06; LD requiring intervention OR, 2.22; 95% CI, 1.03‐4.36). Further, multivariable analysis confirmed the independent association of SSRIs/SNRIs with postoperative LD, which was closely associated with postoperative 90‐day mortality and 1‐year overall survival.

Conclusions
We observed a significant association of perioperative SSRI/SNRI intake with adverse postoperative outcome after hepatic resection. This indicates that SSRIs/SNRIs should be avoided perioperatively in patients undergoing hepatic resections.
Clinical trial risk in leukemia: Biomarkers and trial design
Authors: Li Alice J. , Dhanraj Jasper P. , Lopes Gilberto , Parker Jayson L. 
Published: October 2020

AbstractThis study analyzed the risk of clinical trial failure for leukemia drug development between January 1999 and January 2020. The specific leukemia subtypes of interest were acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Drug development was investigated using data obtained from https://www.clinicaltrials.gov and other publicly available databases. Drug compounds were excluded if they began phase I testing for the indication of interest before January 1999, if they were not industry sponsored, or if they treated secondary complications of the disease. Further analysis was conducted on biomarker usage, drug mechanisms of action, and line of treatment. Drugs were identified following our inclusion criteria for ALL (72), CLL (106), AML (159), and CML (47). The likelihood (cumulative pass rate), a drug would pass all phases of clinical testing and obtain Food and Drug Administration approval, was 18% (ALL), 10% (CLL), 7% (AML), and 12% (CML). Biomarker targeted therapies improved the success rates by three‐ and sevenfold, for ALL and AML, respectively. Enzyme inhibitors doubled the cumulative success rate for AML. First‐line therapy and kinase inhibitors both independently doubled the cumulative success rate for CLL. Oncologists enrolling patients in clinical trials can increase success rates by up to sevenfold by prioritizing participation in trials involving biomarker usage, while consideration of factors such as drug mechanism of action and line of therapy can further double the clinical trial success rate.
Mixed convective heat transfer enhancement in a ventilated cavity by flow modulation via rotating plate
Authors: Islam Aminul , Rony Monoranjan Debnath , Islam Mahmudul , Chowdhury Emdadul Haque , Hasan Mohammad Nasim 
Published: October 2020

AbstractThe present study numerically explores the mixed convection phenomena in a differentially heated ventilated square cavity with active flow modulation via a rotating plate. Forced convection flow in the cavity is attained by maintaining external fluid flow through an opening at the bottom of the left cavity wall while leaving it through another opening at the right cavity wall. A counter‐clockwise rotating plate at the center of the cavity acts as an active flow modulator. Moving mesh approach is used for the rotation of the plate and the numerical solution is achieved using arbitrary Lagrangian‐Eulerian finite element formulation with a quadrilateral discretization scheme. Transient parametric simulations have been performed for various frequency of the rotating plate for a fixed Reynolds number (Re) of 100 based on maximum inlet flow velocity while the Richardson number (Ri) is maintained at unity. Heat transfer performance has been evaluated in terms of spatially averaged Nusselt number and time‐averaged Nusselt number along the heated wall. Power spectrum analysis in the frequency domain obtained from the fast Fourier transform analysis indicates that thermal frequency and plate frequency start to deviate from each other at higher values of velocity ratio (>4).
Role of nuclear factor of activated T cells 2 (NFATc2) in allergic asthma
Authors: Jakobi Marielena , Kiefer Alexander , Mirzakhani Hooman , Rauh Manfred , Zimmermann Theodor , Xepapadaki Paraskevi , Stanic Barbara , Akdis Mubeccel , Papadopoulos Nikolaos G. , Raby Benjamin A. , Weiss Scott T. , Finotto Susetta 
Published: October 2020

AbstractBackgroundWe recently described increased NFATc1, IRF4, and NIP45 messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMCs) of asthmatic children and adults with multiple allergies.ObjectiveNFATc2 has been described to associate with IRF4 to induce interleukin‐4, and to be inhibited by T‐bet. Here, we analyzed the role of NFATc2 in asthmatic children and adults.MethodsPBMCs were isolated from the blood of control of asthmatics subjects. Some PBMCs were analyzed untreated and some cultured with and without phytohemagglutinin. Then, RNA was extracted from the cells and cytokines were measured in the supernatants via enzyme‐linked immunosorbent assay or multiplex analysis. RNA was then reverse‐transcribed and NFATc1, NFATC2, IRF4, and T‐bet mRNA were analyzed by real‐time polymerase chain reaction. In addition, in peripheral blood cells, NFATc2 expression was analyzed, in a population of asthmatic children and adults from the Asthma BRIDGE study.ResultsIn addition to NFATc1 and NIP45, also NFATc2 was found upregulated in PBMCs and peripheral blood cells from asthmatic children and adults with allergic asthma. Moreover, NFATc1 directly correlated with lymphocytes number whereas NFATc2 correlated with peripheral eosinophilia in asthma.ConclusionsIn addition to NFATc1 and NIP45, NFATc2 was found upregulated in asthma. Moreover, NFATc1 mRNA correlated with lymphocytes both in control and asthma, and NFATC1 and NFATc2 mRNA showed a direct correlation with eosinophils in controls but not in asthma, indicating that NFATc1 is associated with lymphocytes and not eosinophils in asthma.Clinical SignificanceTargeting NFATc2 in T lymphocytes might ameliorate the allergic phenotype in asthmatic subjects.