bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different prognostic value of circulating and disseminated tumor cells in primary breast cancer: Influence of bisphosphonate intake?
Authors: Kasimir-Bauer Sabine , Reiter Katharina , Aktas Bahriye , Bittner Ann-Kathrin , Weber Stephan , Keller Thomas , Kimmig Rainer , Hoffmann Oliver 
Published: May 2016

AbstractDisseminated tumor cells (DTCs) in the bone marrow (BM) and circulating tumor cells (CTCs) in blood of breast cancer patients (pts) are known to correlate with worse outcome. Here we demonstrate a different prognostic value of DTCs and CTCs and explain these findings by early clodronate intake. CTCs (n = 376 pts) were determined using the AdnaTest BreastCancer (Qiagen Hannover GmbH, Germany) and DTCs (n = 525 pts) were analyzed by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Clodronate intake was recommended in case of DTC-positivity. CTCs were detected in 22% and DTCs in 40% of the pts, respectively. DTCs were significantly associated with nodal status (p = 0.03), grading (p = 0.01), lymphangiosis (p = 0.03), PR status (p = 0.02) and clodronate intake (p < 0.0001), no significant associations were demonstrated for CTCs. CTCs significantly correlated with reduced PFS (p = 0.0227) and negative prognostic relevance was predominantly related to G2 tumors (p = 0.044), the lobular (p = 0.024) and the triple-negative subtype (p = 0.005), HR-negative pts (p = 0.001), postmenopausal women (p = 0.013) and patients who had received radiation therapy (p = 0.018). No prognostic significance was found for DTCs. Therefore early clodronate intake can improve prognosis of breast cancer patients and CTCs might be a high risk indicator for the onset of metastasis not limited to bone metastasis.
Causes and consequences of intra-specific variation in vertebral number
Authors: Tibblin Petter , Berggren Hanna , Nordahl Oscar , Larsson Per , Forsman Anders 
Published: May 2016

AbstractIntraspecific variation in vertebral number is taxonomically widespread. Much scientific attention has been directed towards understanding patterns of variation in vertebral number among individuals and between populations, particularly across large spatial scales and in structured environments. However, the relative role of genes, plasticity, selection, and drift as drivers of individual variation and population differentiation remains unknown for most systems. Here, we report on patterns, causes and consequences of variation in vertebral number among and within sympatric subpopulations of pike (Esox lucius). Vertebral number differed among subpopulations, and common garden experiments indicated that this reflected genetic differences. A QST-FST comparison suggested that population differences represented local adaptations driven by divergent selection. Associations with fitness traits further indicated that vertebral counts were influenced both by stabilizing and directional selection within populations. Overall, our study enhances the understanding of adaptive variation, which is critical for the maintenance of intraspecific diversity and species conservation.
Correlating the Energetics and Atomic Motions of the Metal-Insulator Transition of M1 Vanadium Dioxide
Authors: Booth Jamie M. , Drumm Daniel W. , Casey Phil S. , Smith Jackson S. , Seeber Aaron J. , Bhargava Suresh K. , Russo Salvy P. 
Published: May 2016

AbstractMaterials that undergo reversible metal-insulator transitions are obvious candidates for new generations of devices. For such potential to be realised, the underlying microscopic mechanisms of such transitions must be fully determined. In this work we probe the correlation between the energy landscape and electronic structure of the metal-insulator transition of vanadium dioxide and the atomic motions occurring using first principles calculations and high resolution X-ray diffraction. Calculations find an energy barrier between the high and low temperature phases corresponding to contraction followed by expansion of the distances between vanadium atoms on neighbouring sub-lattices. X-ray diffraction reveals anisotropic strain broadening in the low temperature structure’s crystal planes, however only for those with spacings affected by this compression/expansion. GW calculations reveal that traversing this barrier destabilises the bonding/anti-bonding splitting of the low temperature phase. This precise atomic description of the origin of the energy barrier separating the two structures will facilitate more precise control over the transition characteristics for new applications and devices.
Polarization induced two dimensional confinement of carriers in wedge shaped polar semiconductors
Authors: Deb S. , Bhasker H. P. , Thakur Varun , Shivaprasad S. M. , Dhar S. 
Published: May 2016

AbstractA novel route to achieve two dimensional (2D) carrier confinement in a wedge shaped wall structure made of a polar semiconductor has been demonstrated theoretically. Tapering of the wall along the direction of the spontaneous polarization leads to the development of charges of equal polarity on the two inclined facades of the wall. Polarization induced negative (positive) charges on the facades can push the electrons (holes) inward for a n-type (p-type) material which results in the formation of a 2D electron (hole) gas at the central plane and ionized donors (acceptors) at the outer edges of the wall. The theory shows that this unique mode of 2D carrier confinement can indeed lead to a significant enhancement of carrier mobility. It has been found that the reduced dimensionality is not the only cause for the enhancement of mobility in this case. Ionized impurity scattering, which is one of the major contributer to carrier scattering, is significantly suppressed as the carriers are naturally separated from the ionized centers. A recent experimental finding of very high electron mobility in wedge shaped GaN nanowall networks has been analyzed in the light of this theoretical reckoning.
Magnesium inference screw supports early graft incorporation with inhibition of graft degradation in anterior cruciate ligament reconstruction
Authors: Cheng Pengfei , Han Pei , Zhao Changli , Zhang Shaoxiang , Zhang Xiaonong , Chai Yimin 
Published: May 2016

AbstractPatients after anterior cruciate ligament (ACL) reconstruction surgery commonly encounters graft failure in the initial phase of rehabilitation. The inhibition of graft degradation is crucial for the successful reconstruction of the ACL. Here, we used biodegradable high-purity magnesium (HP Mg) screws in the rabbit model of ACL reconstruction with titanium (Ti) screws as a control and analyzed the graft degradation and screw corrosion using direct pull-out tests, microCT scanning and histological and immunohistochemical staining. The most noteworthy finding was that tendon graft fixed by HP Mg screws exhibited biomechanical properties substantially superior to that by Ti screws and the relative area of collagen fiber at the tendon-bone interface was much larger in the Mg group, when severe graft degradation was identified in the histological analysis at 3 weeks. Semi-quantitative immunohistochemical results further elucidated that the MMP-13 expression significantly decreased surrounding HP Mg screws with relatively higher Collagen II expression. And HP Mg screws exhibited uniform corrosion behavior without displacement or loosening in the femoral tunnel. Therefore, our results demonstrated that Mg screw inhibited graft degradation and improved biomechanical properties of tendon graft during the early phase of graft healing and highlighted its potential in ACL reconstruction.
Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis
Authors: Wang Hao , Yu Yang , Jiang Zheng , Cao Wen-Ming , Wang Zhenyu , Dou Jun , Zhao Yanling , Cui Yunfu , Zhang Hong 
Published: May 2016

AbstractDoxorubicin (Dox), one of the most effective chemotherapy drug for cancer treatment, is limited by its severe side effects and chemoresistance. Dox induces DNA damage and leads to significant proteomic changes in the cancer cells, which makes the ubiquitin-proteasome system a potential target to enhance the efficacy of Dox therapy. The unsuccessful clinical trials of proteasome inhibitor PS-341 (bortezomib) in solid tumors led to the invention of MLN9708 (ixazomib), an orally bioavailable next-generation proteasome inhibitor with improved pharmacokinetic and pharmacodynamic features. In this preclinical study, we used eight human breast cancer cell lines, which represent the major molecular subtypes of breast cancer, to validate the cytotoxic effects of MLN9708, alone and in combination with Dox. We found that MLN9708 had cytotoxic effects, induced autophagy and MKP-1 expression, and enhanced Dox-induced apoptosis in these cell lines. MLN9708 also enhanced Dox-induced JNK and p38 phosphorylation and inhibited Dox-induced IκBα degradation. Our in vitro results suggest that MLN9708 has antitumor effects in breast cancer and can sensitize breast cancer cells to Dox treatment. This promising combination may be an effective and feasible therapeutic option for treating breast cancer and warrants clinical validation.
Cryopreserved Mesenchymal Stromal Cells Maintain Potency in a Retinal Ischemia/Reperfusion Injury Model: Toward an off-the-shelf Therapy
Authors: Gramlich Oliver W. , Burand Anthony J. , Brown Alex J. , Deutsch Riley J. , Kuehn Markus H. , Ankrum James A. 
Published: May 2016

AbstractThe ability to use mesenchymal stromal cells (MSC) directly out of cryostorage would significantly reduce the logistics of MSC therapy by allowing on-site cryostorage of therapeutic doses of MSC at hospitals and clinics. Such a paradigm would be especially advantageous for the treatment of acute conditions such as stroke and myocardial infarction, which are likely to require treatment within hours after ischemic onset. Recently, several reports have emerged that suggest MSC viability and potency are damaged by cryopreservation. Herein we examine the effect of cryopreservation on human MSC viability, immunomodulatory potency, growth factor secretion and performance in an ischemia/reperfusion injury model. Using modifications of established cryopreservation methods we developed MSC that retain >95% viability upon thawing, remain responsive to inflammatory signals and are able to suppress activated human peripheral blood mononuclear cells. Most importantly, when injected into the eyes of mice 3 hours after the onset of ischemia and 2 hours after the onset of reperfusion, cryopreserved performed as well as fresh MSC to rescue retinal ganglion cells. Thus, our data suggests when viability is maintained throughout the cryopreservation process, MSC retain their therapeutic potency in both in vitro potency assays and an in vivo ischemia/reperfusion model.
Genetic variant in CXCL13 gene is associated with susceptibility to intrauterine infection of hepatitis B virus
Authors: Wan Zhihua , Lin Xiaofang , Li Tongyang , Zhou Aifen , Yang Mei , Hu Dan , Feng Li , Peng Songxu , Fan Linlin , Tu Si , Bin Zhang  , Du Yukai 
Published: May 2016

AbstractIntrauterine infection of hepatitis B virus (HBV), which accounts for the majority of mother-to-child transmission, is one of the main reasons for the failure of combined immunoprophylaxis against the transmission. Recent studies have identified that genetic background might influence the susceptibility to intrauterine infection of HBV. We conducted this study to investigate the associations between 10 genetic variants in 9 genes (SLC10A1, HLA-DP, HLA-C, CXCR5, CXCL13, TLR3, TLR4, TLR9 and UBE2L3) of mothers and their neonates and HBV intrauterine infection. A significantly decreased risk of HBV intrauterine transmission were found among mothers who carried the rs355687 CT genotypes in CXCL13 gene compared to those with CC genotypes (OR = 0.25, 95% CI, 0.08–0.82, P = 0.022); and a marginally significantly decreased risk was also observed under the dominant model (OR = 0.34, 95% CI, 0.11–1.01, P = 0.052). Besides, neonatal rs3130542 in HLA-C gene was found to be marginally significantly associated with decreased risk of HBV intrauterine infection under the additive model (OR = 0.55, 95% CI, 0.29–1.04, P = 0.064). However, we found no evidence of associations between the remaining 8 SNPs and risk of HBV intrauterine infection among mothers and their neonates. In conclusion, this study suggested that genetic variant in CXCL13 gene was associated with susceptibility to intrauterine infection of HBV.
Proline-rich tyrosine kinase 2 via enhancing signal transducer and activator of transcription 3-dependent cJun expression mediates retinal neovascularization
Authors: Kumar Raj , Singh Nikhlesh K. , Rao Gadiparthi N. 
Published: May 2016

AbstractDespite the involvement of proline-rich tyrosine kinase 2 (Pyk2) in endothelial cell angiogenic responses, its role in pathological retinal angiogenesis is not known. In the present study, we show that vascular endothelial growth factor A (VEGFA) induces Pyk2 activation in mediating human retinal microvascular endothelial cell (HRMVEC) migration, sprouting and tube formation. Downstream to Pyk2, VEGFA induced signal transducer and activator of transcription 3 (STAT3) activation and cJun expression in the modulation of HRMVEC migration, sprouting and tube formation. Consistent with these observations, hypoxia induced activation of Pyk2-STAT3-cJun signaling axis and siRNA-mediated downregulation of Pyk2, STAT3 or cJun levels substantially inhibited hypoxia-induced retinal endothelial cell proliferation, tip cell formation and neovascularization. Together, these observations suggest that activation of Pyk2-mediated STAT3-cJun signaling is required for VEGFA-induced HRMVEC migration, sprouting and tube formation in vitro and hypoxia-induced retinal endothelial cell proliferation, tip cell formation and neovascularization in vivo.
Reducing hypoxia and inflammation during invasive pulmonary aspergillosis by targeting the Interleukin-1 receptor
Authors: Gresnigt Mark S. , Rekiki Abdessalem , Rasid Orhan , Savers Amélie , Jouvion Grégory , Dannaoui Eric , Parlato Marianna , Fitting Catherine , Brock Matthias , Cavaillon Jean-Marc , van de Veerdonk Frank L. , Ibrahim-Granet Oumaïma 
Published: May 2016

AbstractHypoxia as a result of pulmonary tissue damage due to unresolved inflammation during invasive pulmonary aspergillosis (IPA) is associated with a poor outcome. Aspergillus fumigatus can exploit the hypoxic microenvironment in the lung, but the inflammatory response required for fungal clearance can become severely disregulated as a result of hypoxia. Since severe inflammation can be detrimental to the host, we investigated whether targeting the interleukin IL-1 pathway could reduce inflammation and tissue hypoxia, improving the outcome of IPA. The interplay between hypoxia and inflammation was investigated by in vivo imaging of hypoxia and measurement of cytokines in the lungs in a model of corticosteroid immunocompromised and in Cxcr2 deficient mice. Severe hypoxia was observed following Aspergillus infection in both models and correlated with development of pulmonary inflammation and expression of hypoxia specific transcripts. Treatment with IL-1 receptor antagonist reduced hypoxia and slightly, but significantly reduced mortality in immunosuppressed mice, but was unable to reduce hypoxia in Cxcr2−/− mice. Our data provides evidence that the inflammatory response during invasive pulmonary aspergillosis and in particular the IL-1 axis, drives the development of hypoxia. Targeting the inflammatory IL-1 response could be used as a potential immunomodulatory therapy to improve the outcome of aspergillosis.
High-performance Fuel Cell with Stretched Catalyst-Coated Membrane: One-step Formation of Cracked Electrode
Authors: Kim Sang Moon , Ahn Chi-Yeong , Cho Yong-Hun , Kim Sungjun , Hwang Wonchan , Jang Segeun , Shin Sungsoo , Lee Gunhee , Sung Yung-Eun , Choi Mansoo 
Published: May 2016

AbstractWe have achieved performance enhancement of polymer electrolyte membrane fuel cell (PEMFC) though crack generation on its electrodes. It is the first attempt to enhance the performance of PEMFC by using cracks which are generally considered as defects. The pre-defined, cracked electrode was generated by stretching a catalyst-coated Nafion membrane. With the strain-stress property of the membrane that is unique in the aspect of plastic deformation, membrane electrolyte assembly (MEA) was successfully incorporated into the fuel cell. Cracked electrodes with the variation of strain were investigated and electrochemically evaluated. Remarkably, mechanical stretching of catalyst-coated Nafion membrane led to a decrease in membrane resistance and an improvement in mass transport, which resulted in enhanced device performance.
Design and Synthesis of Potent in Vitro and in Vivo Anticancer Agents Based on 1-(3′,4′,5′-Trimethoxyphenyl)-2-Aryl-1H-Imidazole
Authors: Romagnoli Romeo , Baraldi Pier Giovanni , Prencipe Filippo , Oliva Paola , Baraldi Stefania , Tabrizi Mojgan Aghazadeh , Lopez-Cara Luisa Carlota , Ferla Salvatore , Brancale Andrea , Hamel Ernest , Ronca Roberto , Bortolozzi Roberta , Mariotto Elena , Basso Giuseppe , Viola Giampietro 
Published: May 2016

AbstractA novel series of tubulin polymerization inhibitors, based on the 1-(3′,4′,5′-trimethoxyphenyl)-2-aryl-1H-imidazole scaffold and designed as cis-restricted combretastatin A-4 analogues, was synthesized with the goal of evaluating the effects of various patterns of substitution on the phenyl at the 2-position of the imidazole ring on biological activity. A chloro and ethoxy group at the meta- and para-positions, respectively, produced the most active compound in the series (4o), with IC50 values of 0.4-3.8 nM against a panel of seven cancer cell lines. Except in HL-60 cells, 4o had greater antiproliferative than CA-4, indicating that the 3′-chloro-4′-ethoxyphenyl moiety was a good surrogate for the CA-4 B-ring. Experiments carried out in a mouse syngenic model demonstrated high antitumor activity of 4o, which significantly reduced the tumor mass at a dose thirty times lower than that required for CA-4P, which was used as a reference compound. Altogether, our findings suggest that 4o is a promising anticancer drug candidate that warrants further preclinical evaluation.
Contextual sensitivity in scientific reproducibility
Authors: Van Bavel Jay J. , Mende-Siedlecki Peter , Brady William J. , Reinero Diego A. 
Published: May 2016

SignificanceScientific progress requires that findings can be reproduced by other scientists. However, there is widespread debate in psychology (and other fields) about how to interpret failed replications. Many have argued that contextual factors might account for several of these failed replications. We analyzed 100 replication attempts in psychology and found that the extent to which the research topic was likely to be contextually sensitive (varying in time, culture, or location) was associated with replication success. This relationship remained a significant predictor of replication success even after adjusting for characteristics of the original and replication studies that previously had been associated with replication success (e.g., effect size, statistical power). We offer recommendations for psychologists and other scientists interested in reproducibility.
Mobile phone data highlights the role of mass gatherings in the spreading of cholera outbreaks
Authors: Finger Flavio , Genolet Tina , Mari Lorenzo , de Magny Guillaume Constantin , Manga Noël Magloire , Rinaldo Andrea , Bertuzzo Enrico 
Published: May 2016

Significance
Big data and, in particular, mobile phone data are expected to revolutionize epidemiology, yet their full potential is still untapped. Here, we take a significant step forward by developing an epidemiological model that accounts for the spatiotemporal patterns of human mobility derived by directly tracking properly anonymized mobile phone users. Such data allow us to investigate, with an unprecedented level of detail, the effect that mass gatherings can have on the spreading of waterborne diseases like cholera. Identifying and understanding transmission hotspots opens the way to the implementation of novel disease control strategies.
Probabilistic population projections with migration uncertainty
Authors: Azose Jonathan J. , Ševčíková Hana , Raftery Adrian E. 
Published: May 2016

SignificanceProjected populations to the end of this century are an important factor in many policy decisions. Population forecasts become less reliable as we look farther into the future, suggesting a probabilistic approach to convey uncertainty. Migration projections have been largely deterministic until now, even in probabilistic population projections. Deterministic migration projections neglect a substantial source of population uncertainty. We incorporate a probabilistic migration model with probabilistic models of fertility and mortality to produce probabilistic population projections for all countries until 2100. The result is a substantial increase in uncertainty about the populations of Europe and Northern America, with very little change to uncertainty about the population of Africa, Asia, and the world as a whole.
A significant hardening and rising shape detected in the MeV/GeV νFν spectrum from the recently discovered very-high-energy blazar S4 0954+65 during the bright optical flare in 2015 February
Authors: Tanaka Yasuyuki T. , Becerra Gonzalez Josefa , Itoh Ryosuke , Finke Justin D. , Inoue Yoshiyuki , Ojha Roopesh , Carpenter Bryce , Lindfors Elina , Krauß Felicia , Desiante Rachele , Shiki Kensei , Fukazawa Yasushi , Longo Francesco , McEnery Julie E. , Buson Sara , Nilsson Kari , Fallah Ramazani Vandad , Reinthal Riho , Takalo Leo , Pursimo Tapio , Boschin Walter 
Published: May 2016

Abstract
We report on Fermi Large Area Telescope (LAT) and multi-wavelength results on the recently discovered very-high-energy (VHE, E &gt; 100 GeV) blazar S4 0954+65 (z = 0.368) during an exceptionally bright optical flare in 2015 February. During the time period (2015 February 13/14, or MJD 57067) when the MAGIC telescope detected VHE γ-ray emission from the source, the Fermi-LAT data indicated a significant spectral hardening at GeV energies, with a power-law photon index of 1.8 ± 0.1—compared with the 3FGL (The Fermi LAT 4-Year Point Source Catalog) value (averaged over four years of observation) of 2.34 ± 0.04. In contrast, Swift X-Ray Telescope data showed a softening of the X-ray spectrum, with a photon index of 1.72 ± 0.08 (compared with 1.38 ± 0.03 averaged during the flare from MJD 57066 to 57077), possibly indicating a modest contribution of synchrotron photons by the highest-energy electrons superposed on the inverse Compton component. Fitting of the quasi-simultaneous (&lt;1 d) broad-band spectrum with a one-zone synchrotron plus inverse-Compton model revealed that GeV/TeV emission could be produced by inverse-Compton scattering of external photons from the dust torus. We emphasize that a flaring blazar showing high flux of ≳1.0 × 10−6 photons cm−2 s−1 (E &gt; 100 MeV) and a hard spectral index of ΓGeV &lt; 2.0 detected by Fermi-LAT on daily timescales is a promising target for TeV follow-up by ground-based Cherenkov telescopes to discover high-redshift blazars, investigate their temporal variability and spectral features in the VHE band, and also constrain the intensity of the extragalactic background light.