bluuebunny/crossref_metadata_2025_split huggingface dataset:
HPV vaccine status and sexual behavior among young sexually-active women in the US: evidence from the National Health and Nutrition Examination Survey, 2007–2014
Authors: Leidner Andrew J. , Chesson Harrell W. , Talih Makram 
Published: May 2019

AbstractConcern has been expressed that human papillomavirus (HPV) vaccination programs might promote risky sexual behavior through mechanisms such as risk compensation, behavioral disinhibition, or perceived endorsement of sexual activity. This study assesses whether HPV vaccination status is associated with any differences in selected sexual behaviors among young sexually-active women in the US. Our dataset includes young, adult female respondents from questionnaire data collected in the National Center for Health Statistics' National Health and Nutrition Examination Survey from 2007 to 2014. The empirical approach implements a doubly robust estimation procedure, based on inverse probability of treatment weighting. For robustness, we implement several specifications for the propensity model and the outcomes model. We find no consistent association between HPV vaccination and condom usage or frequency of sex. Specifically, we find no evidence that HPV vaccination is associated with condom usage or with whether a person had sex more than 52 or more than 104 times per year. We find inconsistent evidence that HPV vaccination is associated with a person having sex more than 12 times per year. As in previous research, HPV vaccination does not appear to have a substantive effect on sexual behavior among young sexually-active women in the US.
Transdiagnostic CBT for adult emotional disorders: A feasibility open trial from Saudi Arabia
Authors: Alatiq Yousra , Al Modayfer Omar 
Published: May 2019

AbstractTransdiagnostic cognitive behavioural therapy (T-CBT) provides potential for improving psychotherapy services in countries with limited resources. The primary aim of this study was to assess the feasibility and potential benefits of using T-CBT in Saudi Arabia to treat adult emotional disorders in a naturalistic open trial. A secondary aim was to measure the effect of this approach when delivered by junior psychologists as a low-intensity intervention. The overall sample consisted of 198 patients (160 in the low-intensity group). Only 33 (16.7%) patients had completed the treatment plan, 55 (27.3%) were still active in treatment, and 109 (55%) had disengaged from the treatment. The pre- and post-assessments for the clients who completed the treatment showed a significant decrease in all outcome measures. This result held true for the whole sample and the low-intensity group. This study provides initial evidence that T-CBT is suitable for clients with emotional disorders in Saudi Arabia. The study also provides support for the effect of T-CBT as a low-intensity intervention delivered by junior psychologists. However, one of the study limitations was the sample size for the group who completed the treatment and was properly discharged from service. Implications and recommendations are discussed.Key learning aims(1)To examine the feasibility and potential benefits of using T-CBT in Saudi Arabia.(2)To measure the effect of T-CBT as low-intensity interventions delivered by junior psychologists.(3)To establish evidence-based practice for T-CBT in Saudi Arabia.
Global Governance, Sustainability and the Earth System: Critical Reflections on the Role of Global Law
Authors: Cardesa-Salzmann Antonio , Cocciolo Endrius 
Published: May 2019

AbstractThis article begins by questioning the capacity of the concept of sustainable development to stabilize social reproduction and foster global justice. Based on interdisciplinary perspectives on global governance, it discusses the way in which global law fails to cope with the resonance of advanced capitalism in the world society and ecological systems. Our analysis focuses on the regulatory and institutional features of three interwoven functional regulatory regimes (global finance, energy, and environmental protection), which demonstrate structural governance dysfunction at the expense of ecological integrity and justice in the global realm. The article further examines the capacity of global law to foster a ‘compositive’ and ‘compensatory’ contribution to global justice and the stability of the Earth system through global constitutionalism. In this context, it concludes that Neil Walker's global law approach provides a fertile analytical framework for describing the patterns of interaction between different species of global law but proves to be particularly ‘slippery’ in its normative propositions regarding the gap between global law and justice. Drawing from the Earth system approach, we argue in favour of a global material constitutionalism, recognizant of ecosystemic boundaries and socio-environmental impacts of the global socio-economic metabolism. We consider that the gap between global law and global justice is best addressed by devising more deliberative patterns of transnational governance, as well as ecosystem and human rights approaches, in order to accommodate the fair and equitable internalization of material limits across global regulatory regimes that act as functionally differentiated economic constitutions of advanced capitalism.
North Atlantic Sub‐Polar Gyre Climate Index: A New Approach
Authors: Biri Stavroula , Klein Birgit 
Published: May 2019

AbstractAs decadal predictions become operational, the need to use, understand, and extract information from them becomes essential. A climate index is a simple diagnostic quantity that can be used to characterize integral aspects of a geophysical system such as circulation patterns, and thus can be used to evaluate decadal forecasts. One of the most studied and well documented regions of the World Ocean is the North Atlantic. The North Atlantic subpolar gyre is an important region for the modulation of European climate and where skillful predictions of up to a decade can be obtained. Ocean re‐analysis (ORA‐S4) data from 1959 to 2017 are used to introduce a new methodology to compute a climate index of the North Atlantic subpolar gyre that captures both the variability in its strength and shape, the latter was to our knowledge never investigated previously as part of the variability of the gyre on interannual to decadal time scales. The methodology reveals two states of the gyre (before and after 2000), the former is mainly driven by temperature and the latter by a combination of mechanisms that interact to sustain a relatively stable subpolar gyre in terms of strength.
Vapor‐Deposited Minerals Contributed to the Martian Surface During Magmatic Degassing
Authors: Nekvasil H. , DiFrancesco N. J. , Rogers A. D. , Coraor A. E. , King P. L. 
Published: May 2019

AbstractMartian magmas were likely enriched in S and Cl with respect to H2O. Exsolution of a vapor phase from these magmas and ascent of the gas bubbles through the magma plumbing system would have given rise to shallow magmas that were gas‐charged. Release and cooling of this gas from lava flows during eruption may have resulted in the addition of a significant amount of vapor‐deposited phases to the fines of the surface. Experiments were conducted to simulate degassing of gas‐charged lava flows and shallow intrusions in order to determine the nature of vapor‐deposited phases that may form through this process. The results indicate that magmatic gas may have contributed a large amount of Fe, S, and Cl to the Martian surface through the deposition of iron oxides (magnetite, maghemite, and hematite), chlorides (molysite, halite, and sylvite), sulfur, and sulfides (pyrrhotite and pyrite). Primary magmatic vapor‐deposited minerals may react during cooling to form a variety of secondary products, including iron oxychloride (FeOCl), akaganéite (Fe3+O (OH,Cl)), and jarosite (KFe3+3(OH)6(SO4)2). Vapor‐deposition does not transport significant amounts of Ca, Al, or Mg from the magma and hence, this process does not directly deposit Ca‐ or Mg‐sulfates.
Climate Change Feedbacks in Aquaplanet Experiments With Explicit and Parametrized Convection for Horizontal Resolutions of 2,525 Up to 5 km
Authors: Retsch M. H. , Mauritsen T. , Hohenegger C. 
Published: May 2019

AbstractEarth's equilibrium climate sensitivity (ECS) is the long‐term response to doubled atmospheric CO2 and likely between 1.5 and 4.5 K. Conventional general circulation models do not convincingly narrow down this range, and newly developed nonhydrostatic models with relatively fine horizontal resolutions of a few kilometers have thus far delivered diverse results. Here we use the nonhydrostatic ICON model with the physics package normally used for climate simulations at resolutions as fine as 5 km to study the response to a uniform surface warming in an aquaplanet configuration. We apply the model in two setups: one with convection parametrization employed and one with explicit convection. ICON exhibits a negative total feedback independent of convective representation, thus providing a stable climate with an ECS comparable to other general circulation models, though three interesting new results are found. First, ECS varies little across resolution for both setups but runs with explicit convection have systematically lower ECS than the parametrized case, mainly due to more negative tropical clear‐sky longwave feedbacks. These are a consequence of a drier mean state of about 6% relative humidity for explicit convection and less midtropospheric moistening with global warming. Second, shortwave feedbacks switch from positive to negative with increasing resolution, originating foremost in the tropics and high latitudes. Third, the model shows no discernible high cloud area feedback (iris effect) in any configuration. It is possible that ICON's climate model parametrizations applied here are less appropriate for cloud resolving scales, and therefore, ongoing developments aim at implementing a more advanced prognostic cloud microphysics scheme.
ABCB1 SNP predicts outcome in patients with acute myeloid leukemia treated with Gemtuzumab ozogamicin: a report from Children’s Oncology Group AAML0531 Trial
Authors: Rafiee Roya , Chauhan Lata , Alonzo Todd A. , Wang Yi-Cheng , Elmasry Ahlam , Loken Michael R. , Pollard Jessica , Aplenc Richard , Raimondi Susana , Hirsch Betsy A. , Bernstein Irwin D. , Gamis Alan S. , Meshinchi Soheil , Lamba Jatinder K. 
Published: May 2019

AbstractGemtuzumab-ozogamicin (GO), a humanized-anti-CD33 antibody linked with the toxin-calicheamicin-γ is a reemerging and promising drug for AML. Calicheamicin a key element of GO, induces DNA-damage and cell-death once the linked CD33-antibody facilitates its uptake. Calicheamicin efflux by the drug-transporter PgP-1 have been implicated in GO response thus in this study, we evaluated impact of ABCB1-SNPs on GO response. Genomic-DNA samples from 942 patients randomized to receive standard therapy with or without addition of GO (COG-AAML0531) were genotyped for ABCB1-SNPs. Our most interesting results show that for rs1045642, patients with minor-T-allele (CT/TT) had better outcome as compared to patients with CC genotype in GO-arm (Event-free survival-EFS: p = 0.022; and risk of relapse-RR, p = 0.007). In contrast, no difference between genotypes was observed for any of the clinical endpoints within No-GO arm (all p > 0.05). Consistent results were obtained when genotype groups were compared by GO and No-GO arms. The in vitro evaluation using HL60-cells further demonstrated consistent impact of rs1045642-T-allele on calicheamicin induced DNA-damage and cell-viability. Our results show the significance of ABCB1 SNPs on GO response in AML and warrants the need to investigate this in other cohorts. Once validated, ABCB1-SNPs in conjunction with CD33-SNPs can open up opportunities to personalize GO-therapy.
Dendritic cell-associated B7-H3 suppresses the production of autoantibodies and renal inflammation in a mouse model of systemic lupus erythematosus
Authors: Zheng Xu , Xiao Ze Xiu , Hu Li , Fang Xuan , Luo Liqun , Chen Lieping 
Published: May 2019

AbstractB7-H3 immune modulatory molecule has been implicated in the generation and pathogenesis of autoimmune diseases, the mechanism of action is less known. We explored the role of B7-H3 in the induction of autoantibodies and organ-directed inflammation in a murine systemic lupus erythematosus (SLE) model in which the immunization with DNA extracted from activated T cells induced the production of anti-DNA autoantibodies and subsequent glomerulonephritis, two hallmarks of human SLE. Mice deficient of B7-H3 or treated with a B7-H3 specific antibody produced significantly higher levels of anti-DNA autoantibodies and more severe glomerulonephritis than wild-type mice, indicating an inhibitory function of B7-H3 in this model. Interestingly, immunization of mice with DNA-pulsed dendritic cells induced severe SLE symptoms while B7-H3 on dendritic cells is required in this process. Importantly, treatment of mice with recombinant B7-H3Ig fusion protein effectively ameliorated progression of murine SLE, accompanied with decreased level of anti-DNA autoantibodies and alleviated glomerulonephritis, decreased autoantibody deposition and complement deposition in kidney. Our findings implicate a potential role of B7-H3 on dendritic cells in the induction of SLE and as a potential target for the treatment of autoimmune diseases.
A novel UCHL3 inhibitor, perifosine, enhances PARP inhibitor cytotoxicity through inhibition of homologous recombination-mediated DNA double strand break repair
Authors: Song Zhiwang , Tu Xinyi , Zhou Qin , Huang Jinzhou , Chen Yuping , Liu Jiaqi , Lee SeungBaek , Kim Wootae , Nowsheen Somaira , Luo Kuntian , Yuan Jian , Lou Zhenkun 
Published: May 2019

AbstractTriple-negative breast cancer (TNBC) treatment remains a great challenge for clinical practice and novel therapeutic strategies are urgently needed. UCHL3 is a deubiquitinase that is overexpressed in TNBC and correlates with poor prognosis. UCHL3 deubiquitinates RAD51 thereby promoting the recruitment of RAD51 to DNA damage sites and augmenting DNA repair. Therefore, UCHL3 overexpression can render cancer cells resistant to DNA damage inducing chemo and radiotherapy, and targeting UCHL3 can sensitize TNBC to radiation and chemotherapy. However, small molecule inhibitors of UCHL3 are yet to be identified. Here we report that perifosine, a previously reported Akt inhibitor, can inhibit UCHL3 in vitro and in vivo. We found low dose (50 nM) perifosine inhibited UCHL3 deubiquitination activity without affecting Akt activity. Furthermore, perifosine enhanced Olaparib-induced growth inhibition in TNBC cells. Mechanistically, perifosine induced RAD51 ubiquitination and blocked the RAD51-BRCA2 interaction, which in turn decreased ionizing radiation-induced foci (IRIF) of Rad51 and, thereby, homologous recombination (HR)-mediated DNA double strand break repair. In addition, combination of perifosine and Olaparib showed synergistic antitumor activity in vivo in TNBC xenograft model. Thus, our present study provides a novel therapeutic approach to optimize PARP inhibitor treatment efficiency.
Coordinated representational reinstatement in the human hippocampus and lateral temporal cortex during episodic memory retrieval
Authors: Pacheco Estefan D. , Sánchez-Fibla M. , Duff A. , Principe A. , Rocamora R. , Zhang H. , Axmacher N. , Verschure P. F. M. J. 
Published: May 2019

AbstractTheoretical models of episodic memory have proposed that retrieval depends on interactions between the hippocampus and neocortex, where hippocampal reinstatement of item-context associations drives neocortical reinstatement of item information. Here, we simultaneously recorded intracranial EEG from hippocampus and lateral temporal cortex (LTC) of epilepsy patients who performed a virtual reality spatial navigation task. We extracted stimulus-specific representations of both item and item-context associations from the time-frequency patterns of activity in hippocampus and LTC. Our results revealed a double dissociation of representational reinstatement across time and space: an early reinstatement of item-context associations in hippocampus preceded a later reinstatement of item information in LTC. Importantly, reinstatement levels in hippocampus and LTC were correlated across trials, and the quality of LTC reinstatement was predicted by the magnitude of phase synchronization between hippocampus and LTC. These findings confirm that episodic memory retrieval in humans relies on coordinated representational interactions within a hippocampal-neocortical network.
Seismic evidence for a mantle suture and implications for the origin of the Canadian Cordillera
Authors: Chen Yunfeng , Gu Yu Jeffrey , Currie Claire A. , Johnston Stephen T. , Hung Shu-Huei , Schaeffer Andrew J. , Audet Pascal 
Published: May 2019

AbstractThe origin of the North American Cordillera and its affinity with the bounding craton are subjects of contentious debate. The mechanisms of orogenesis are rooted in two competing hypotheses known as the accretionary and collisional models. The former model attributes the Cordillera to an archetypal accretionary orogen comprising a collage of exotic terranes. The latter, less popular view argues that the Cordillera is a collisional product between an allochthonous ribbon microcontinent and cratonic North America. Here we present new seismic evidence of a sharp and structurally complex Cordillera–craton boundary in the uppermost mantle beneath the southern Canadian Cordillera, which can be interpreted as either a reshaped craton margin or a Late Cretaceous collisional boundary based on the respective hypotheses. This boundary dips steeply westward underneath a proposed (cryptic) suture in the foreland, consisent with the predicted location and geometry of the mantle suture, thus favoring a collisional origin.
The extracellular gate shapes the energy profile of an ABC exporter
Authors: Hutter Cedric A. J. , Timachi M. Hadi , Hürlimann Lea M. , Zimmermann Iwan , Egloff Pascal , Göddeke Hendrik , Kucher Svetlana , Štefanić Saša , Karttunen Mikko , Schäfer Lars V. , Bordignon Enrica , Seeger Markus A. 
Published: May 2019

AbstractABC exporters harness the energy of ATP to pump substrates across membranes. Extracellular gate opening and closure are key steps of the transport cycle, but the underlying mechanism is poorly understood. Here, we generated a synthetic single domain antibody (sybody) that recognizes the heterodimeric ABC exporter TM287/288 exclusively in the presence of ATP, which was essential to solve a 3.2 Å crystal structure of the outward-facing transporter. The sybody binds to an extracellular wing and strongly inhibits ATPase activity by shifting the transporter’s conformational equilibrium towards the outward-facing state, as shown by double electron-electron resonance (DEER). Mutations that facilitate extracellular gate opening result in a comparable equilibrium shift and strongly reduce ATPase activity and drug transport. Using the sybody as conformational probe, we demonstrate that efficient extracellular gate closure is required to dissociate the NBD dimer after ATP hydrolysis to reset the transporter back to its inward-facing state.
Impaired cerebellar Purkinje cell potentiation generates unstable spatial map orientation and inaccurate navigation
Authors: Lefort Julie Marie , Vincent Jean , Tallot Lucille , Jarlier Frédéric , De Zeeuw Chris Innocentius , Rondi-Reig Laure , Rochefort Christelle 
Published: May 2019

AbstractCerebellar activity supported by PKC-dependent long-term depression in Purkinje cells (PCs) is involved in the stabilization of self-motion based hippocampal representation, but the existence of cerebellar processes underlying integration of allocentric cues remains unclear. Using mutant-mice lacking PP2B in PCs (L7-PP2B mice) we here assess the role of PP2B-dependent PC potentiation in hippocampal representation and spatial navigation. L7-PP2B mice display higher susceptibility to spatial map instability relative to the allocentric cue and impaired allocentric as well as self-motion goal-directed navigation. These results indicate that PP2B-dependent potentiation in PCs contributes to maintain a stable hippocampal representation of a familiar environment in an allocentric reference frame as well as to support optimal trajectory toward a goal during navigation.
ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes
Authors: Fang Caodi , Manes Thomas D. , Liu Lufang , Liu Kevin , Qin Lingfeng , Li Guangxin , Tobiasova Zuzana , Kirkiles-Smith Nancy C. , Patel Manal , Merola Jonathan , Fu Whitney , Liu Rebecca , Xie Catherine , Tietjen Gregory T. , Nigrovic Peter A. , Tellides George , Pober Jordan S. , Jane-wit Dan 
Published: May 2019

AbstractComplement promotes vascular inflammation in transplant organ rejection and connective tissue diseases. Here we identify ZFYVE21 as a complement-induced Rab5 effector that induces non-canonical NF-κB in endothelial cells (EC). In response to membrane attack complexes (MAC), ZFYVE21 is post-translationally stabilized on MAC+Rab5+ endosomes in a Rab5- and PI(3)P-dependent manner. ZFYVE21 promotes SMURF2-mediated polyubiquitinylation and proteasome-dependent degradation of endosome-associated PTEN to induce vesicular enrichment of PI(3,4,5)P3 and sequential recruitment of activated Akt and NF-κB-inducing kinase (NIK). Pharmacologic alteration of cellular phosphoinositide content with miltefosine reduces ZFYVE21 induction, EC activation, and allograft vasculopathy in a humanized mouse model. ZFYVE21 induction distinctly occurs in response to MAC and is detected in human renal and synovial tissues. Our data identifies ZFYVE21 as a Rab5 effector, defines a Rab5-ZFYVE21-SMURF2-pAkt axis by which it mediates EC activation, and demonstrates a role for this pathway in complement-mediated conditions.
The Kibble-Zurek mechanism at exceptional points
Authors: Dóra Balázs , Heyl Markus , Moessner Roderich 
Published: May 2019

AbstractExceptional points (EPs) are ubiquitous in non-Hermitian systems, and represent the complex counterpart of critical points. By driving a system through a critical point at finite rate induces defects, described by the Kibble-Zurek mechanism, which finds applications in diverse fields of physics. Here we generalize this to a ramp across an EP. We find that adiabatic time evolution brings the system into an eigenstate of the final non-Hermitian Hamiltonian and demonstrate that for a variety of drives through an EP, the defect density scales as τ−(d + z)ν/(zν + 1) in terms of the usual critical exponents and 1/τ the speed of the drive. Defect production is suppressed compared to the conventional Hermitian case as the defect state can decay back to the ground state close to the EP. We provide a physical picture for the studied dynamics through a mapping onto a Lindblad master equation with an additionally imposed continuous measurement.