bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of PARP Inhibitor Rucaparib in Orthotopic Glioblastoma Xenografts Is Limited by Ineffective Drug Penetration into the Central Nervous System
Authors: Parrish Karen E. , Cen Ling , Murray James , Calligaris David , Kizilbash Sani , Mittapalli Rajendar K. , Carlson Brett L. , Schroeder Mark A. , Sludden Julieann , Boddy Alan V. , Agar Nathalie Y.R. , Curtin Nicola J. , Elmquist William F. , Sarkaria Jann N. 
Published: October 2015

Abstract
PARP inhibition can enhance the efficacy of temozolomide and prolong survival in orthotopic glioblastoma (GBM) xenografts. The aim of this study was to evaluate the combination of the PARP inhibitor rucaparib with temozolomide and to correlate pharmacokinetic and pharmacodynamic studies with efficacy in patient-derived GBM xenograft models. The combination of rucaparib with temozolomide was highly effective in vitro in short-term explant cultures derived from GBM12, and, similarly, the combination of rucaparib and temozolomide (dosed for 5 days every 28 days for 3 cycles) significantly prolonged the time to tumor regrowth by 40% in heterotopic xenografts. In contrast, the addition of rucaparib had no impact on the efficacy of temozolomide in GBM12 or GBM39 orthotopic models. Using Madin-Darby canine kidney (MDCK) II cells stably expressing murine BCRP1 or human MDR1, cell accumulation studies demonstrated that rucaparib is transported by both transporters. Consistent with the influence of these efflux pumps on central nervous system drug distribution, Mdr1a/b−/−Bcrp1−/− knockout mice had a significantly higher brain to plasma ratio for rucaparib (1.61 ± 0.25) than wild-type mice (0.11 ± 0.08). A pharmacokinetic and pharmacodynamic evaluation after a single dose confirmed limited accumulation of rucaparib in the brain is associated with substantial residual PARP enzymatic activity. Similarly, matrix-assisted laser desorption/ionization mass spectrometric imaging demonstrated significantly enhanced accumulation of drug in flank tumor compared with normal brain or orthotopic tumors. Collectively, these results suggest that limited drug delivery into brain tumors may significantly limit the efficacy of rucaparib combined with temozolomide in GBM. Mol Cancer Ther; 14(12); 2735–43. ©2015 AACR.
PARP Inhibitors Sensitize Ewing Sarcoma Cells to Temozolomide-Induced Apoptosis via the Mitochondrial Pathway
Authors: Engert Florian , Schneider Cornelius , Weiβ Lilly Magdalena , Probst Marie , Fulda Simone 
Published: October 2015

AbstractEwing sarcoma has recently been reported to be sensitive to poly(ADP)-ribose polymerase (PARP) inhibitors. Searching for synergistic drug combinations, we tested several PARP inhibitors (talazoparib, niraparib, olaparib, veliparib) together with chemotherapeutics. Here, we report that PARP inhibitors synergize with temozolomide (TMZ) or SN-38 to induce apoptosis and also somewhat enhance the cytotoxicity of doxorubicin, etoposide, or ifosfamide, whereas actinomycin D and vincristine show little synergism. Furthermore, triple therapy of olaparib, TMZ, and SN-38 is significantly more effective compared with double or monotherapy. Mechanistic studies revealed that the mitochondrial pathway of apoptosis plays a critical role in mediating the synergy of PARP inhibition and TMZ. We show that subsequent to DNA damage-imposed checkpoint activation and G2 cell-cycle arrest, olaparib/TMZ cotreatment causes downregulation of the antiapoptotic protein MCL-1, followed by activation of the proapoptotic proteins BAX and BAK, mitochondrial outer membrane permeabilization (MOMP), activation of caspases, and caspase-dependent cell death. Overexpression of a nondegradable MCL-1 mutant or BCL-2, knockdown of NOXA or BAX and BAK, or the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) all significantly reduce olaparib/TMZ-mediated apoptosis. These findings emphasize the role of PARP inhibitors for chemosensitization of Ewing sarcoma with important implications for further (pre)clinical studies. Mol Cancer Ther; 14(12); 2818–30. ©2015 AACR.
Frequent Dilatation of the Descending Aorta in Children With Hypoplastic Left Heart Syndrome Relates to Decreased Aortic Arch Elasticity
Authors: Voges Inga , Jerosch‐Herold Michael , Wegner Philip , Hart Christopher , Gabbert Dominik , Al Bulushi Abdullah , Fischer Gunther , Andrade Ana Cristina , Pham Hoang Minh , Kristo Ines , Kramer Hans‐Heiner , Rickers Carsten 
Published: October 2015

Background

Patients with hypoplastic left heart syndrome after a Norwood operation show dilatation and reduced distensibility of the reconstructed proximal aorta. Cardiac magnetic resonance imaging (
CMR
) and angiographic examinations indicate that the native descending aorta (
DA
o) is also dilated, but this has not been studied in detail.

Methods and Results

Seventy‐nine children with hypoplastic left heart syndrome in Fontan circulation (aged 6.3±3.2 years) and 18 control participants (aged 6.8±2.4 years) underwent 3.0‐tesla
CMR
. Gradient‐echo cine and phase‐contrast imaging was applied to measure cross‐sectional areas (
CSA
s), distensibility, pulse wave velocity, and the incremental elastic modulus of the thoracic aorta.
CSA
of the
DA
o in patients was also compared with published percentiles for aortic
CSA
. Patients had significantly larger
CSA
of the
DA
o at the level of pulmonary artery bifurcation (229.1±97.2 versus 175.7±24.3 mm/m
2
,
P
=0.04) and the diaphragm (196.2±66.0 versus 142.6±16.7 mm/m
2
,
P
<0.01). In 41 patients (52%),
CSA
of the
DA
o was >95th percentile level for control participants, and the incremental elastic modulus of the aortic arch and the
DA
o was higher than in patients with normal
CSA
s (arch: 90.1±64.3 versus 45.6±38.9 m/s;
DA
o: 86.3±53.7 versus 47.1±47.6 m/s;
P
<0.01). Incremental elastic modulus of the aortic arch and the
DA
o correlated with the
CSA
of the
DA
o (arch:
r
=0.5;
DA
o:
r
=0.49;
P
<0.01).

Conclusions

Children with hypoplastic left heart syndrome frequently show dilatation of their
DA
o associated with increased stiffness of the aortic arch. Higher aortic impedance increases the afterload of the systemic circulation and likely contributes to the burden of the systemic right ventricle.
Liposarcoma of the cord treated with surgery alone: Our experience of five patients
Authors: Chan Dedrick Kok Hong , Durai Pradeep , Parameswaran Rajeev 
Published: October 2015

Background: Liposarcoma of the spermatic cord is a rare condition presenting as an inguinal or scrotal mass. We describe our experience in the management of five patients diagnosed with this disease. Methods: We conducted a retrospective analysis of patients who underwent treatment for the condition between 2011 and 2014. Demographic data collected included the patient’s age, presentation, site of tumour, tumour size and grade and World Health Organisation (WHO) histotypes. Adequacy of tumour resection and the use of adjuvant chemotherapy or radiotherapy were also recorded. The study end points included duration of disease-free survival (DFS) as well as overall survival (OS). Results: During the study period we identified five patients with a diagnosis of liposarcoma of the cord with a median age of 67 (range 33–72) years. Three patients presented with primary disease and two were diagnosed post-resection and required re-excision to obtain R0 resection margins. Three patients had well-differentiated and two patients had dedifferentiated liposarcoma. None of the patients required adjuvant chemotherapy or radiotherapy following achievement of R0 resection margins and developed loco-regional recurrence or distant metastases. Median DFS was 30 (range 10–45) months. Conclusion: Liposarcomas of the cord are rare soft-tissue sarcomas with a high incidence of recurrence. Treatment of choice is radical orchidectomy, wide excision of the tumour and high ligation of the spermatic cord. Long-term follow-up is necessary.
Remotely-delivered cognitive remediation in multiple sclerosis (MS): protocol and results from a pilot study
Authors: Charvet LE , Shaw MT , Haider L , Melville P , Krupp LB 
Published: October 2015

Background Cognitive impairment represents a critical unmet treatment need in multiple sclerosis (MS). Cognitive remediation is promising but traditionally requires multiple clinic visits to access treatment. Computer-based programs provide remote access to intensive and individually-adapted training. Objective Our goal was to develop a protocol for remotely-supervised cognitive remediation that enables individuals with MS to participate from home while maintaining the standards for clinical study. Methods MS participants ( n = 20) were randomized to either an active cognitive remediation program ( n = 11) or a control condition of ordinary computer games ( n = 9). Participants were provided study laptops to complete training for five days per week over 12 weeks, targeting a total of 30 hours. Treatment effects were measured with composite change via scores of a repeated neuropsychological battery. Results Compliance was high with an average of 25.0 hours of program use (80% of the target) and did not differ between conditions (25.7 vs. 24.2 mean hours, p = 0.80). The active vs. control participants significantly improved in both the cognitive measures (mean composite z-score change of 0.46 ± 0.59 improvement vs. −0.14 ± 0.48 decline, p = 0.02) and motor tasks (mean composite z-score change of 0.40 ± 0.71improvement vs. −0.64 ± 0.73 decline, p = 0.005). Conclusions Remotely-supervised cognitive remediation is feasible for clinical study with potential for meaningful benefit in MS.
Minimal amounts of kindlin-3 suffice for basal platelet and leukocyte functions in mice
Authors: Klapproth Sarah , Moretti Federico A. , Zeiler Marlis , Ruppert Raphael , Breithaupt Ute , Mueller Susanna , Haas Rainer , Mann Matthias , Sperandio Markus , Fässler Reinhard , Moser Markus 
Published: October 2015

Key Points
As little as 5% of kindlin-3 is sufficient to maintain basal platelet and leukocyte functions. Platelets and neutrophils contain stoichiometric quantities of kindlin-3 and talin-1.
Integration of molecular cytogenetics, dated molecular phylogeny, and model-based predictions to understand the extreme chromosome reorganization in the Neotropical genus Tonatia (Chiroptera: Phyllostomidae)
Authors: Sotero-Caio Cibele G. , Volleth Marianne , Hoffmann Federico G. , Scott LuAnn , Wichman Holly A. , Yang Fengtang , Baker Robert J. 
Published: October 2015

Abstract
Background
Defining factors that contributed to the fixation of a high number of underdominant chromosomal rearrangements is a complex task because not only molecular mechanisms must be considered, but also the uniqueness of natural history attributes of each taxon. Ideally, detailed investigation of the chromosome architecture of an organism and related groups, placed within a phylogenetic context, is required. We used multiple approaches to investigate the dynamics of chromosomal evolution in lineages of bats with considerable karyotypic variation, focusing on the different facets contributing to fixation of the exceptional chromosomal changes in Tonatia saurophila. Integration of empirical data with proposed models of chromosome evolution was performed to understand the probable conditions for Tonatia’s karyotypic evolution.

Results
The trajectory of reorganization of chromosome blocks since the common ancestor of Glossophaginae and Phyllostominae subfamilies suggests that multiple tandem fusions, as well as disruption and fusions of conserved phyllostomid chromosomes were major drivers of karyotypic reshuffling in Tonatia. Considerable variation in the rates of chromosomal evolution between phyllostomid lineages was observed. Thirty–nine unique fusions and fission events reached fixation in Tonatia over a short period of time, followed by ~12 million years of chromosomal stasis. Physical mapping of repetitive DNA revealed an unusual accumulation of LINE-1 sequences on centromeric regions, probably associated with the chromosomal dynamics of this genus.

Conclusions
Multiple rearrangements have reached fixation in a wave-like fashion in phyllostomid bats. Different biological features of Tonatia support distinct models of rearrangement fixation, and it is unlikely that the fixations were a result of solely stochastic processes in small ancient populations. Increased recombination rates were probably facilitated by expansion of repetitive DNA, reinforced by aspects of taxon reproduction and ecology.
Iterative methods for solving the multiple-sets split feasibility problem with splitting self-adaptive step size
Authors: Tang Yuchao , Zhu Chuanxi , Yu Hui 
Published: October 2015

AbstractWe introduce an iterative algorithm for solving the multiple-sets split feasibility problem with splitting self-adaptive step size. This step size is calculated directly from the iteration process without need to know the spectral norm of linear operators. We also generalize the chosen step size to a relaxed iterative algorithm. Theoretical convergence is proved in an infinite dimensional Hilbert space. Some numerical experiments are presented to verify the effectiveness of our proposed methods.
Recent results on the topological fixed point theory of multivalued mappings: a survey
Authors: Andres Jan , Górniewicz Lech 
Published: October 2015

AbstractIn this survey, we present current results from the topological fixed point theory of multivalued mappings which were obtained by ourselves in the last five years (see Andres and Górniewicz in Fixed Point Theory 12(2):255-264, 2011; Topol. Methods Nonlinear Anal. 40:337-358, 2012; Libertas Mathematica 33(1):69-78, 2013; Int. J. Bifurc. Chaos 24(11):1450148, 2014; J. Nonlinear Convex Anal. 16(6):1013-1023, 2015; Int. J. Bifurc. Chaos, 2015, to appear). Some abstract theorems are applied to differential inclusions and multivalued fractals. A part of the deterministic theory is randomized, including the applications to random differential inclusions.
Randomized Multicenter Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (DCF) Versus DCF Plus Growth Factor Support in Patients With Metastatic Gastric Adenocarcinoma: A Study of the US Gastric Cancer Consortium
Authors: Shah Manish A. , Janjigian Yelena Y. , Stoller Ronald , Shibata Stephen , Kemeny Margaret , Krishnamurthi Smitha , Su Yungpo Bernard , Ocean Allyson , Capanu Marinela , Mehrotra Bhoomi , Ritch Paul , Henderson Charles , Kelsen David P. 
Published: October 2015

Purpose Docetaxel, cisplatin, and fluorouracil (DCF) is a standard first-line three-drug chemotherapy regimen for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma and is associated with significant toxicity. We examined the safety and efficacy of a modified DCF (mDCF) regimen in a randomized multicenter phase II study. Patients and Methods Previously untreated patients with metastatic gastric or GEJ adenocarcinoma were randomly assigned to receive either mDCF (fluorouracil 2,000 mg/m2 intravenously [IV] over 48 hours, docetaxel 40 mg/m2 IV on day 1, cisplatin 40 mg/m2 IV on day 3, every 2 weeks) or parent DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, and fluorouracil 750 mg/m2 IV over 5 days with granulocyte colony-stimulating factor, every 3 weeks). The study had 90% power to differentiate between 6-month progression-free survival of 26% and 43%, with type I and II error rates of 10% each. An early stopping rule for toxicity was included, defined as grade 3 to 4 adverse event rate > 70% in the first 3 months. Results From November 2006 to June 2010, 85 evaluable patients were enrolled (male, n = 61; female, n = 24; median age, 58 years; Karnofsky performance status, 90%; GEJ, n = 28; gastric, 57). mDCF (n = 54) toxicity rates included 54% grade 3 to 4 toxicity (22% hospitalized) within the first 3 months and 76% grade 3 to 4 toxicity over the course of treatment. The DCF arm (n = 31) closed early because of toxicity, with rates of 71% grade 3 to 4 toxicity (52% hospitalized) within 3 months and 90% grade 3 to 4 toxicity over the course of treatment. Six-month PFS was 63% (95% CI, 48% to 75%) for mDCF and 53% (95% CI, 34% to 69%) for DCF. Median overall survival was improved for mDCF (18.8 v 12.6 months; P = .007). Conclusion mDCF is less toxic than parent DCF, even when supported with growth factors, and is associated with improved efficacy. mDCF should be considered a standard first-line option for patients with metastatic gastric or GEJ adenocarcinoma.
Gender disparities: assessment and treatment of coronary heart disease
Authors: Hamill Sarah , Ingram Nigel 
Published: October 2015

Aim:The aim of this study was to evaluate and summarise the current evidence base in relation to the gender-specific presentation and assessment of coronary heart disease.Background:Coronary heart disease (CHD) is one of the leading causes of death in both men and women worldwide. There remains a common misconception that CHD is predominantly a ‘man's disease’ and that CHD doesn't affect women until they are much older. Much of the evidence base is underpinned by male-based population studies.Design:A systematic review of current qualitative and quantitative primary research literature was used to establish if coronary heart disease patients would benefit from a gender-specific approach. Data Sources: Cochrane library (1898–2014), PubMed (1996–2014), MEDLINE (1946–2014), AMED (1985–2014), Embase (1974–2014), CINAHL (1937–2014), British Nursing Index (1994 – 2014), PsycINFO (1800–2014).Results:Selected studies were reviewed in English and critiqued in accordance with the critical review framework used by the National Institute for Health and Care Excellence.Conclusion:There are clear differences between the genders in relation to coronary heart disease. It is imperative that nursing practice acknowledges this through the greater application of gender-specific care.
Constructions of complete sets
Authors: Papini Pier Luigi , Wu Senlin 
Published: October 2015

Abstract
Constructing constant width sets or, more generally, complete sets in Banach spaces seems to be a not so easy task. A new construction working in separable Banach spaces is presented, and Bavaud’s and Lachand-Robert and Oudet’s constructions of complete sets are extended to a more general context.
On the geometrical properties of solvable Lie groups
Authors: Aghasi Mansour , Nasehi Mehri 
Published: October 2015

Abstract
In [3] Bozek introduced a class of solvable Lie groups M2n+1. Calvaruso, Kowalski and Marinosci in [9] have studied homogeneous geodesics on these homogeneous spaces with an arbitrary odd dimension. In [1] we have studied some other geometrical properties on these spaces with dimension five. Our aim in this paper is to extend those geometrical properties for an arbitrary odd dimension in both Riemannian and Lorentzian cases. In fact we first obtain all of the descriptions of their homogeneous Lorentzian and Riemannian structures and their types. Then we calculate the energy of an arbitrary left-invariant vector field X on these spaces and in the Lorentzian case we prove that no left-invariant unit time-like vector fields on these spaces are critical points for the space-like energy. There is also a proof of non-existence of invariant contact structures and left-invariant Ricci solitons on these homogeneous spaces.
The Log-Convex Density Conjecture and vertical surface area in warped products
Authors: Howe Sean 
Published: October 2015

Abstract
We examine the vertical component of surface area in the warped product of a Euclidean interval and a fiber manifold with product density.We determine general conditions under which vertical fibers minimize vertical surface area among regions bounding the same volume and use these results to conclude that in many such spaces vertical fibers are isoperimetric. Our main hypothesis is that the surface area of a fiber be a convex function of the volume it bounds. We apply our results in the specific case of ℝn − {0} realized as the warped product (0, ∞) ×r Sn−1, providing many new examples of densities where spheres about the origin are isoperimetric, including simple densities with finite volume, simple densities that at the origin are neither log-convex nor smooth, and non-simple densities. We also generalize the results of Kolesnikov and Zhdanov on large balls in Rn with increasing strictly log-convex simple density. We situate our work in relation to the Log-Convex Density Conjecture of Rosales et al. and the recent work by Morgan, Ritoré, and others on formulating a generalized log-convex density/stable spheres conjecture.
Locally Monge–Ampère parabolic foliations
Authors: Kalka Morris , Patrizio Giorgio 
Published: October 2015

Abstract
It is shown that codimension one parabolic foliations of complex manifolds are holomorphic. This is proved using the facts that codimension one foliations of complex manifolds are necessarily locally Monge- Ampère foliations and that parabolic leaves cannot have hyperbolic behavior. The result holds true also for locally Monge-Ampère foliations with parabolic leaves of arbitrary codimension.
Real open books and real contact structures
Authors: Öztürk Ferit , Salepci Nermin 
Published: October 2015

Abstract
A real 3-manifold is a smooth 3-manifold together with an orientation preserving smooth involution, called a real structure. In this article we study open book decompositions on smooth real 3-manifolds that are compatible with the real structure.We call them real open book decompositions.We show that each real open book carries a real contact structure and two real contact structures supported by the same real open book decomposition are equivariantly isotopic. We also show that every real contact structure on a closed 3-dimensional real manifold is supported by a real open book. Finally, we conjecture that two real open books on a real contact manifold supporting the same real contact structure are related by positive real stabilizations and equivariant isotopy, and that the Giroux correspondence applies to real manifolds as well, namely that there is a one-to-one correspondence between the real contact structures on a real 3-manifold up to equivariant contact isotopy and the real open books up to positive real stabilization. Meanwhile, we study some examples of real open books and real Heegaard decompositions in lens spaces.
Magnetorelaxometry procedures for quantitative imaging and characterization of magnetic nanoparticles in biomedical applications
Authors: Liebl Maik , Wiekhorst Frank , Eberbeck Dietmar , Radon Patricia , Gutkelch Dirk , Baumgarten Daniel , Steinhoff Uwe , Trahms Lutz 
Published: October 2015

AbstractQuantitative knowledge about the spatial distribution and local environment of magnetic nanoparticles (MNPs) inside an organism is essential for guidance and improvement of biomedical applications such as magnetic hyperthermia and magnetic drug targeting. Magnetorelaxometry (MRX) provides such quantitative information by detecting the magnetic response of MNPs following a fast change in the applied magnetic field.In this article, we review our MRX based procedures that enable both the characterization and the quantitative imaging of MNPs in a biomedical environment.MRX characterization supported the selection of an MNP system with colloidal stability and suitable cellular MNP uptake. Spatially resolved MRX, a procedure employing multi-channel MRX measurements allowed forThese MRX based measurement and analysis procedures have substantially supported the development of MNP based biomedical applications.