bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological inhibition of the MEK5/ERK5 and PI3K/Akt signaling pathways synergistically reduces viability in triple‐negative breast cancer
Authors: Wright Thomas D. , Raybuck Christopher , Bhatt Akshita , Monlish Darlene , Chakrabarty Suravi , Wendekier Katy , Gartland Nathan , Gupta Mohit , Burow Matthew E. , Flaherty Patrick T. , Cavanaugh Jane E. 
Published: August 2019

AbstractTriple‐negative breast cancers (TNBCs) represent 15% to 20% of all breast cancers and are often associated with poor prognosis. The lack of targeted therapies for TNBCs contributes to higher mortality rates. Aberrations in the phosphoinositide‐3‐kinase (PI3K) and mitogen‐activated protein kinase pathways have been linked to increased breast cancer proliferation and survival. It has been proposed that these survival characteristics are enhanced through compensatory signaling and crosstalk mechanisms. While the crosstalk between PI3K and extracellular signal‐regulated kinase 1/2 (ERK1/2) pathways has been characterized in several systems, new evidence suggests that MEK5/ERK5 signaling is a key component in the proliferation and survival of several aggressive cancers. In this study, we examined the effects of dual inhibition of PI3K/protein kinase B (Akt) and MEK5/ERK5 in the MDA‐MB‐231, BT‐549, and MDA‐MB‐468 TNBC cell lines. We used the Akt inhibitor ipatasertib, ERK5 inhibitors XMD8‐92 and AX15836, and the novel MEK5 inhibitor SC‐1‐181 to investigate the effects of dual inhibition. Our results indicated that dual inhibition of PI3K/Akt and MEK5/ERK5 signaling was more effective at reducing the proliferation and survival of TNBCs than single inhibition of either pathway alone. In particular, a loss of Bad phosphorylation at two distinct sites was observed with dual inhibition. Furthermore, the inhibition of both pathways led to p21 restoration, decreased cell proliferation, and induced apoptosis. In addition, the dual inhibition strategy was determined to be synergistic in MDA‐MB‐231 and BT‐549 cells and was relatively nontoxic in the nonneoplastic MCF‐10 cell line. In summary, the results from this study provide a unique prospective into the utility of a novel dual inhibition strategy for targeting TNBCs.
Results From a First‐in‐Human Study of BNZ‐1, a Selective Multicytokine Inhibitor Targeting Members of the Common Gamma (γc) Family of Cytokines
Authors: Frohna Paul A. , Ratnayake Anoshie , Doerr Nick , Basheer Asjad , Al‐Mawsawi Laith Q. , Kim Woo Jae , Zapata Juan C. , Wu Xiaorong , Waldmann Thomas A. , Azimi Nazli , Tagaya Yutaka 
Published: August 2019

AbstractPathologic roles of interleukin (IL)‐2, IL‐9, and IL‐15, have been implicated in multiple T‐cell malignancies and autoimmune diseases. BNZ‐1 is a selective and simultaneous inhibitor of IL‐2, IL‐9, and IL‐15, which targets the common gamma chain signaling receptor subunit. In this first‐in‐human study, 18 healthy adults (n = 3/cohort) received an intravenous dose of 0.2, 0.4, 0.8, 1.6, 3.2, or 6.4 mg/kg infused over ≤5 minutes on day 1 and were followed for 30 days for safety and pharmacokinetic/pharmacodynamic sample collection. No dose‐limiting toxicities, infusion reactions, or serious or severe treatment‐emergent adverse events were observed. Headache was the only treatment‐emergent adverse event in >1 subject (n = 3). Peak and total BNZ‐1 exposure was generally dose proportional, with a terminal elimination half‐life of ∼5 days. Pharmacodynamic effects of BNZ‐1 on regulatory T cells (Tregs, IL‐2), natural killer (NK) cells (IL‐15) and CD8 central memory T cells (Tcm, IL‐15) were measured by flow cytometry and used to demonstrate target engagement. For Tregs, 0.2 mg/kg was an inactive dose, while a maximum ∼50% to 60% decrease from baseline was observed on day 4 after doses of 0.4 to 1.6 mg/kg, and higher doses produced an 80% to 93% decrease from baseline on day 15. Similar pharmacodynamic trends were observed for natural killer cells and CD8 Tcm, although decreases in CD8 Tcm were more prolonged. These subpopulations returned to/toward baseline by day 31. T cells (total, CD4, and CD8), B cells, and monocytes were unchanged throughout. These preliminary results suggest that BNZ‐1 safely and selectively inhibits IL‐2 and IL‐15, which results in robust, reversible immunomodulation.
Impact assessment and investigation of factors associated with herpesviruses viremia in the first year of renal transplantation
Authors: Savassi‐Ribas Flavia , Gomes dos Santos de Almeida Stéphanie , Baez Camila Freze , Magalhães de Souza Leandro , Wagner Tereza Cristina Simão , Matuck Tereza Azevedo , Monteiro de Carvalho Deise De Boni , Marandino Guimarães Maria Angelica Arpon , Varella Rafael Brandão 
Published: August 2019

AbstractThe increased risk for opportunistic infections after a renal transplant requires monitoring of viral infections to avoid future complications. Our goal was to investigate the impact and factors associated with Epstein‐Barr virus (EBV), human cytomegalovirus (HCMV) and human herpesvirus type 6 (HHV‐6) viremia in renal transplant recipients. Whole blood samples were collected monthly from 82 patients during the first semester and then quarterly up to 1 year after transplantation. EBV, HCMV, and HHV‐6 were detected and quantified by TaqMan real‐time polymerase chain reaction. The results showed that EBV and HCMV viremia were detected in 32 patients (39% each), while HHV‐6 viremia in only 3 patients (3.7%). EBV was significantly associated with age (P = .050), thymoglobuline induction (P = .019), mTOR inhibitor‐based therapy (P = .003), and female gender (P = .044). HCMV was significantly associated with basiliximab induction (P = .015), mycophenolate mofetil (MMF)‐based therapy (P = .003) and allograft acute rejection (P = .033). Moreover, HCMV‐disease was correlated with MMF‐based therapy (P = .021) and female gender (P = .003). In conclusion, EBV and HCMV viremia were associated with different immunosuppressive induction and maintenance strategies. Additionally, higher HCMV viremia (> 10
4 copies/mL) was related to acute allograft rejection.
The decision‐making process in viral marketing—A review and suggestions for further research
Authors: Reichstein Thomas , Brusch Ines 
Published: August 2019

AbstractViral marketing is used to widely distribute content. To achieve this goal, the basic decision‐making process from content reception to interaction must be clarified. This paper examines the decision‐making process of individuals in viral marketing using a new dynamic model. In addition, this work reviews the existing literature on viral marketing and structures to identify existing issues for further research. The decision‐making process is basically divided into two stages. In the first decision stage, individuals decide whether content should be considered. When individuals agree to view the content, they decide in the second stage whether they want to interact with it. These two decisions are influenced by three factors: the framework conditions, content, and interaction aims. With the help of the decision model, this paper summarizes the most important findings from viral marketing research over the last 20 years. In addition, this work provides new opportunities for further research in the field of viral marketing.
Side differences in the degree of mosaicism of the buccal mucosa in Turner syndrome
Authors: Thunström Sofia , Landin‐Wilhelmsen Kerstin , Bryman Inger , Hanson Charles 
Published: August 2019

AbstractBackgroundThe aim was to investigate if there were any differences in the degree of mosaicism between the left‐ and right‐hand sides of the buccal mucosa in women with Turner syndrome.MethodsBuccal smears were taken on the left‐ and right‐hand sides at the same time for genetic analyses with fluorescence in situ hybridization in women with Turner syndrome, n = 20; 10 with and 10 without mosaicism based on the blood karyotype, and one control. A difference in the degree of mosaicism ≥5% between the sides was considered as an actual difference and <5% as equivalent.ResultsOf 20, 10 (50%) had ≥ 5% difference in the degree of mosaicism between the left‐ and right‐hand sides of the buccal mucosa. The mean difference was 9.1% and the median was 4.5%, range 1%–38%. The control with ordinary female karyotype had no side difference.ConclusionThere was an intraorganic mosaicism of the buccal mucosa with a side difference in the degree of mosaicism of up to 38% in women with Turner syndrome. When mosaicism is strongly suspected, but not confirmed by the blood karyotype, it is recommended that buccal smears from both sides of the oral cavity should be analyzed.
A novel LAMP2 p.G93R mutation associated with mild Danon disease presenting with familial hypertrophic cardiomyopathy
Authors: Xu Jing , Wang Lu , Liu Xiangdong , Dai Qiming 
Published: August 2019

AbstractBackgroundDanon disease (DD) is an X‐linked dominant multisystem disorder that is associated with cardiomyopathy, skeletal myopathy, and varying degrees of intellectual disability. It results from mutations in the lysosome‐associated membrane protein 2 (LAMP2) gene.MethodsHerein, a proband with a mild DD case presenting with a familial hypertrophic cardiomyopathy (HCM) phenotype and additional family members were evaluated. Exome sequencing and Sanger sequencing were performed to explore the genetic basis of DD in the proband. Segregation, in silico, and functional analyses were carried out to explore potential pathogenicity in the candidate mutation.ResultsExome sequencing and Sanger sequencing identified one novel missense mutation (p.G93R) in the LAMP2 gene in the proband, and this mutation was also identified in three other family members. In silico analysis of LAMP2 predicted that the mutation causes a conformational change and subsequent protein destabilization. Furthermore, functional examination showed that mutation carriers have a significant reduction in LAMP2 expression, which supports that the mutation is pathogenic. Moreover, skewed X chromosome inactivation (XCI) was identified in one female mutation carrier, thus suggesting that skewed XCI may be the reason why this individual escaped the pathogenic influence of the mutation.ConclusionThese findings will aid in diagnosing DD patients carrying this LAMP2 mutation that presents with a HCM phenotype. Furthermore, this study illustrates the importance of utilizing a molecular diagnostic approach in HCM patients and is the first study to report a LAMP2 p.G93R mutation associated with mild DD and identify that XCI serves a protective role in DD etiology.
Compact dual‐band implantable planar inverted‐F antenna with bandwidth enhancement
Authors: Shang Jiangli , Yu Ying , Xu Li‐Jie 
Published: August 2019

AbstractIn this paper, a miniaturized planar inverted‐F antenna (PIFA) with a volume of 49.5 mm3 is proposed for biomedical implantable devices, operating in Medical Implant Communications Service (MICS, 402‐405 MHz) band and Industrial, Scientific, and Medical (ISM, 2.40‐2.48 GHz) band. It has a wide operating bandwidth in MICS band. The initial PIFA is designed with dual‐band performance, where the lower band is formed by quarter‐guided‐wavelength resonance and the higher band is formed by two‐guided‐wavelength resonance. Furthermore, by etching open‐slots between short and feed on the ground, a new resonance is introduced and moved towards the fundamental one, expanding the bandwidth in MICS band. Also, the introduction of slots lowers the initial resonant frequency in higher band, meeting the frequency demands of ISM band. Finally, the proposed antenna is measured in pork as well as skin‐mimicking gels, showing a bandwidth of 50.7% and 38% in MICS band, and 13.9% and 6.9% in ISM band.
A polarization reconfigurable discontinuous ring dipole antenna
Authors: Saraswat Kapil , Harish Ayyangar R. 
Published: August 2019

AbstractA circularly polarized antenna is realized using a discontinuous ring dipole. With the introduction of p‐i‐n diodes, it has been possible to achieve polarization reconfigurability in the antenna. The antenna is fed by a tapered feed line, which also acts as a balun and biasing structure. The sense of rotation of the electric field vector (left‐hand or right‐hand) can be controlled by switching the states of the diodes. An equivalent circuit of the antenna is proposed, which has been used to compute the input reflection coefficient of the antenna. The performance of the antenna is verified by comparing the simulated results with the measured results. It has been observed that the antenna has 8.56% overlapping CP bandwidth (a common bandwidth for |S11| ≤ −10 dB and axial ratio, AR ≤3 dB) from 5.03to 5.48 GHz. A measured gain of 3.61 dBic is obtained for all polarization states. The proposed antenna can be used for the 5.2 GHz Wi‐Fi application.
Microarray Profiling and Coexpression Network Analysis of Long Noncoding RNAs in Adipose Tissue of Obesity‐T2DM Mouse
Authors: Yao Zhenyu , Liu Chang , Yu Xiangfang , Meng Jun , Teng Bin , Sun Yutao , Kerem Goher , Ismayil Aynur , Fang Peng , Zhang Jian V. , Ren Pei‐Gen 
Published: August 2019

ObjectiveThe aim of this study was to understand more about long noncoding RNAs (lncRNAs) as potential prediction biomarkers or therapeutic targets for obesity and type 2 diabetes mellitus (T2DM). This study aimed to find more lncRNA candidates related to obesity and T2DM.MethodsIn this study, a high‐fat diet (HFD)‐induced obesity‐T2DM mouse model was used, and a mRNA and lncRNA expression map was drawn up in adipose tissue by microarray technology. Then Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed and revealed that the most associated genes and pathways were metabolism‐related ones. The candidate lncRNA expression was further validated in adipose tissue from HFD‐induced mice by quantitative real‐time polymerase chain reaction analysis.ResultsTranscriptome analyses were performed to show expression profiles of mRNAs and lncRNAs in epididymal adipose tissue in the obesity‐T2DM mice. A total of 124 lncRNAs and 1,606 mRNAs were differentially expressed between the chow and HFD groups. Then, an mRNA‐lncRNA coexpression network was constructed. Based on a series of analyses, 15 candidate lncRNAs were screened, and their expression was further validated by quantitative real‐time polymerase chain reaction analysis.ConclusionsThe results reveal significant differences between the transcriptomes of the HFD and control groups in adipose tissue that provide clues to the molecular mechanisms of diet‐induced metabolic disorders as well as biomarkers of risk for these disorders.
Induced α,γ‐cyclic peptide rotodimer recognition by nucleobase scaffolds
Authors: Panciera Michele , González‐Freire Eva , Calvelo Martín , Amorín Manuel , Granja Juan R. 
Published: August 2019

AbstractThe β‐sheet‐type structures derived from the stacking of α,γ‐cyclic peptides to form peptides nanotubes can provide different topoisomers, nonequivalent cyclic peptide stacks generated by the relative rotation through the channel axis of one cyclic peptide with respect to the next component. This rotation generates a series of cyclic peptide dimers paired by the same type of hydrogen bond pattern but differentiated by the cross‐strand side chain‐side chain pairwise. The control of this peptide‐peptide relative orientation in stacked supramolecular aggregates is required for practical applications in material sciences, sensing, or biology. We propose the use of small oligonucleotides to control the prevalence of a particular dimer through the formation of specific hydrogen bonds between cyclic peptides bearing a nucleobase attached to a serine side chain with a complementary oligonucleotide (peptide nucleic acid).
Mindfulness‐based interventions for psychological and physical health outcomes in cancer patients and survivors: A systematic review and meta‐analysis of randomized controlled trials
Authors: Cillessen Linda , Johannsen Maja , Speckens Anne E.M. , Zachariae Robert 
Published: August 2019

AbstractObjectiveMindfulness‐based interventions (MBIs) are increasingly used within psycho‐oncology. Since the publication of the most recent comprehensive meta‐analysis on MBIs in cancer in 2012, the number of published trials has more than doubled. We therefore conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs), testing the efficacy of MBIs on measures of psychological distress (primary outcome) and other health outcomes in cancer patients and survivors.MethodsTwo authors conducted independent literature searches in electronic databases from first available date to 10 October 2018, selected eligible studies, extracted data for meta‐analysis, and evaluated risk of bias.ResultsTwenty‐nine independent RCTs (reported in 38 papers) with 3274 participants were included. Small and statistically significant pooled effects of MBIs on combined measures of psychological distress were found at post‐intervention (Hedges's g = 0.32; 95%CI: 0.22‐0.41; P < .001) and follow‐up (g = 0.19; 95%CI: 0.07‐0.30; P < .002). Statistically significant effects were also found at either post‐intervention or follow‐up for a range of self‐reported secondary outcomes, including anxiety, depression, fear of cancer recurrence, fatigue, sleep disturbances, and pain (g: 0.20 to 0.51; p: <.001 to.047). Larger effects of MBIs on psychological distress were found in studies (a) adhering to the original MBI manuals, (b) with younger patients, (c) with passive control conditions, and (d) shorter time to follow‐up. Improvements in mindfulness skills were associated with greater reductions in psychological distress at post‐intervention.ConclusionsMBIs appear efficacious in reducing psychological distress and other symptoms in cancer patients and survivors. However, many of the effects were of small magnitude, suggesting a need for intervention optimization research.
Characterisation of phenylethanoid glycosides by multiple‐stage mass spectrometry
Authors: Kite Geoffrey C. 
Published: August 2019

RationaleAlthough phenylethanoid glycosides (PhGs) occur widely in plants, their characterisation by liquid chromatography/mass spectrometry (LC/MS) is less well studied than other phenolic glycosides such as flavonoid glycosides. The multiple‐stage mass spectrometry (MSn) experiments required to improve the annotation of common verbascoside‐type PhGs are described here.MethodsDeprotonated, ammoniated and sodiated molecules of nine PhGs were subjected to low‐energy collision‐induced dissociation (CID) in a hybrid ion trap/orbitrap mass spectrometer. Most experiments were recorded at nominal mass using the linear ion trap analyser for wider applicability in the plant metabolomics community. Data interpretation was supported by high‐resolution orbitrap scanning of product ions. Comparative data was acquired on the same instrument by performing higher‐energy collisional dissociation (HCD) in the C‐trap.ResultsLow‐energy CID‐MS2 of the deprotonated and ammoniated molecules generated diagnostic product ions from which the molecular masses of the phenolic acid and phenylethanoid moieties, respectively, could be determined. The sugar at C‐3′ of the core glucose was preferentially lost from the sodiated molecule following CID‐MS2, while CID‐MSn produced a sodiated product ion from ring cleavage of the core glucose bearing the sugar at C‐6′. Evidence of a disaccharide substitution came from a sodiated disaccharide residue in CID‐MSn spectra.ConclusionsThe consistency of PhG dissociation following low‐energy CID‐MSn of various ions is sufficient to enable annotation of verbascoside‐type PhGs in LC/MS analyses of crude plant extracts. This can be achieved on a low‐resolution instrument capable of MSn.
Input/output‐to‐state stability of nonlinear impulsive delay systems based on a new impulsive inequality
Authors: Jiang Bangxin , Lu Jianquan , Li Xiaodi , Qiu Jianlong 
Published: August 2019

SummaryIn this paper, input/output‐to‐state stability (IOSS) and integral IOSS (iIOSS) are investigated for nonlinear impulsive systems with delay. Based on a new impulsive inequality, we propose some sufficient criteria for IOSS and iIOSS of impulsive delay systems. It is shown that the obtained results for IOSS and iIOSS are regardless of the length of the impulsive interval and the size of time delay if the impulsive gain satisfies a given condition. In addition, based on the average impulsive interval method, some more useful sufficient conditions are derived for IOSS and iIOSS of impulsive delay systems with persistent large‐scale destabilizing impulses. Furthermore, a relationship is established among the average impulsive interval, impulses, time delay, and the decay of the system without impulses such that the impulsive delay system is input/output‐to‐state stable and integral input/output‐to‐state stable, respectively. Two examples are given to show the validity of the obtained results.
Delaminating Vanadium Carbides for Zinc‐Ion Storage: Hydrate Precipitation and H+/Zn2+ Co‐Action Mechanism
Authors: Wang Changda , Wei Shiqiang , Chen Shuangming , Cao Dengfeng , Song Li 
Published: August 2019

AbstractAqueous zinc (Zn) ion energy devices have demonstrated remarkable significance as a substitute of their lithium counterparts. Developing cheap and nontoxic electrode active materials is crucial for maximizing the storage of Zn ions. As a new star of 2D materials, MXenes can pose unique layered structure and abundant surface chemistry, largely benefiting the surface storage of ions. Herein, carbon nanotube (CNT) delaminated V2C MXene (DV2C@CNT) has been demonstrated, as a promising electrode for high‐performance Zn‐ion supercapacitor. The as‐prepared DV2C@CNT electrodes display favorable electrochemical activity with reversible proton (H+) and Zn ion (Zn2+) co‐insertion/extraction process in ZnSO4 solutions. Due to the superior conductive network formed by CNT, the delaminated MXene exhibit a high specific capacity of 190.2 F g−1 at 0.5 A g−1 with excellent rate performance and durability. More interestingly, the characterizations clearly reveal that zinc hydroxide sulfate hydrate nanoflakes can immediately precipitate onto the electrode even at the initial assembly process, which can be ascribed to the spontaneous formation of the electrostatic field in the primary battery. The operando X‐ray absorption spectroscopic measurements further confirm the dynamic hydrate precipitation during charging/discharging cycles, offering a better understanding of energy storage mechanism in Zn‐ion devices with MXene electrodes.
Fatigue behavior of prefatigued reinforced concrete beams rehabilitated with near surface mounted carbon fiber reinforced polymer reinforcement
Authors: Eljufout Tamer , Toutanji Houssam 
Published: August 2019

AbstractThis paper investigates the influence of cyclic preloading on the fatigue behavior of reinforced concrete (RC) beams rehabilitated with near surface mounted (NSM) carbon fiber reinforced polymer (CFRP) reinforcement. The study includes eight RC beams with dimensions of 152.4 × 152.4 × 1,521 mm. Strengthened and nonstrengthened specimens were tested under monotonic loading to obtain the flexural static capacity. Two strengthened specimens were tested as a reference under constant amplitude cyclic stress without prefatiguing. Four nonrehabilitated RC beams were prefatigued to simulate service loading conditions. Later, these RC beams were rehabilitated with NSM CFRP reinforcement and tested under the same cyclic stress range of the reference specimens. Mid‐span deflection, strain of tension steel rebars and CFRP rods, stiffness degradation, and energy dissipation were analyzed and evaluated. Experimental results show that the rehabilitated prefatigued RC beams had similar stiffness degradation and failure modes to the reference strengthened RC beams. The rehabilitated RC beams had an improvement in the fatigue responses when compared to the reference strengthened RC beams. Moreover, the postfatigue monotonic behavior of the rehabilitated RC beams showed an increase in the elastic modulus and a decrease in ductility.