bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal stromal cells loaded with paclitaxel induce cytotoxic damage in glioblastoma brain xenografts
Authors: Pacioni Simone , D’Alessandris Quintino Giorgio , Giannetti Stefano , Morgante Liliana , De Pascalis Ivana , Coccè Valentina , Bonomi Arianna , Pascucci Luisa , Alessandri Giulio , Pessina Augusto , Falchetti Maria Laura , Pallini Roberto 
Published: October 2015

Abstract
Introduction
The goal of cancer chemotherapy is targeting tumor cells and/or tumor-associated microvessels with the lowest systemic toxicity. Mesenchymal stromal cells (MSCs) are promising vehicles for selective drug delivery due to their peculiar ability to home to pathological tissues. We previously showed that MSCs are able to uptake and subsequently to release the chemotherapeutic compound Paclitaxel (PTX) and to impair the growth of subcutaneous glioblastoma multiforme (GBM) xenografts. Here we used an orthotopic GBM model 1) to assess whether PTX-loaded MSCs (PTX-MSCs) retain a tropism towards the tumor cells in the brain context, and 2) to characterize the cytotoxic damage induced by MSCs-driven PTX release in the tumor microenvironment.

Methods
U87MG GBM cells were fluorescently labeled with the mCherry protein and grafted onto the brain of immunosuppressed rats. In adjacent brain regions, we injected green fluorescent protein-expressing murine MSCs, either loaded with PTX or unloaded. After 1 week survival, the xenografted brain was assessed by confocal microscopy for PTX-induced cell damage.

Results
Overall, MSCs showed remarkable tropism towards the tumor. In rats grafted with PTX-MSCs, the nuclei of U87MG cells showed changes that are typically induced by PTX, including multi-spindle mitoses, centrosome number alterations, and nuclear fragmentation. Multi-spindle mitoses resulted in multinucleated cells that were significantly higher in tumors co-grafted with PTX-MSCs than in controls. Nuclear changes did not occur in astrocytes and neurons surrounding the tumor.

Conclusions
MSCs appear particularly suited for anti-neoplastic drug delivery in the brain since PTX-specific damage of GBM cells can be achieved avoiding side effects to the normal tissue.
On fixed point theory in topological posets, extended quasi-metric spaces and an application to asymptotic complexity of algorithms
Authors: Shahzad Naseer , Valero Oscar , Alghamdi Mohammed A , Alghamdi Maryam A 
Published: October 2015

AbstractIn this paper we present a few fixed point results in the framework of topological posets. To this end, we introduce an appropriate notion of completeness and order-continuity. Special attention is paid to the case that the topology of the topological poset is induced by an extended quasi-metric. Finally, the applicability of the exposed results is illustrated providing a methodology to determine the asymptotic upper bound of the complexity of those algorithms whose running time of computing is the solution to a special type of recurrence equation.
Projective contractions, generalized metrics, and fixed points
Authors: Alghamdi Maryam A , Shahzad Naseer , Valero Oscar 
Published: October 2015

AbstractIn 1981, Borsík and Doboš studied the aggregation problem for metric spaces. Thus, they characterized those functions that allow one to merge a collection of metrics providing a single metric as a result (Borsík and Doboš in Math. Slovaca 31:193-205, 1981).Later on, in 1994, the notion of partial metric space was introduced by Matthews with the aim of providing an appropriate mathematical tool for program verification (Matthews in Ann. N.Y. Acad. Sci. 728:183-197, 1994). In the aforesaid reference, an extension of the well-known Banach fixed point theorem to the partial metric framework was given and, in addition, an application of such a result to denotational semantics and program verification was provided.Inspired by the applicability of partial metric spaces to computer science and by the fact that there are partial metrics useful in such a field which can be induced through aggregation, in 2012 Massanet and Valero analyzed the aggregation problem in the partial metric framework (Massanet and Valero in Proc. of the 17th Spanish Conference on Fuzzy Technology and Fuzzy Logic (Estylf 2012), pp.558-563, 2012).In this paper, motivated by the fact that fixed point techniques are essential in order to apply partial metric spaces to computer science and that, as we have pointed out above, some of such partial metrics can be induced by aggregation, we introduce a new notion of contraction between partial metric spaces which involves aggregation functions. Besides, since fixed point theory in partial metric spaces from an aggregation viewpoint still is without exploring, we provide a fixed point theorem in the spirit of Matthews for the new type of contractions and, in addition, we give examples which illustrate that the assumptions in such a result cannot be weakened. Furthermore, we provide conditions that vouch the existence and uniqueness of fixed point for this new class of contractions. Finally, we discuss the well-posedness for this kind of fixed point problem and the limit shadowing property for the new sort of contractions.
Hybrid iterative algorithms for two families of finite maximal monotone mappings
Authors: Qiu Yang-Qing , Ceng Lu-Chuan , Chen Jin-Zuo , Hu Hui-Ying 
Published: October 2015

AbstractIn this paper, we introduce and analyze a new general hybrid iterative algorithm for finding a common element of the set of common zeros of two families of finite maximal monotone mappings, the set of fixed points of a nonexpansive mapping and the set of solutions of the variational inequality problem for a monotone, Lipschitz-continuous mapping in a real Hilbert space. Our algorithm is based on four well-known methods: Mann’s iteration method, composite method, outer-approximation method and extragradient method. We prove the strong convergence theorem for the proposed algorithm. The results presented in this paper extend and improve the corresponding results of Wei and Tan (Fixed Point Theory Appl. 2014:77, 2014). Some special cases are also discussed.
A fixed point iterative approach to integer programming and its distributed computation
Authors: Dang Chuangyin , Ye Yinyu 
Published: October 2015

AbstractInteger programming is concerned with the determination of an integer or mixed-integer point in a polytope. It is an NP-hard problem and has many applications in economics and management. Although several popular methods have been developed for integer programming in the literature and extensively utilized in practices, it remains a challenging problem and appeals for more endeavors. By constructing an increasing mapping satisfying certain properties, we develop in this paper an alternative method for integer programming, which is called a fixed point iterative method. Given a polytope, the method, within a finite number of iterations, either yields an integer or mixed-integer point in the polytope or proves no such point exists. As a very appealing feature, the method can easily be implemented in a distributed way. Furthermore, the construction implies that determining the uniqueness of Tarski’s fixed point is an NP-hard problem, and the method can be applied to compute all integer or mixed-integer points in a polytope and directly extended to convex nonlinear integer programming. Preliminary numerical results show that the method seems promising.
Incidence, diagnosis and management of tubal and nontubal ectopic pregnancies: a review
Authors: Panelli Danielle M. , Phillips Catherine H. , Brady Paula C. 
Published: October 2015

AbstractBackgroundEctopic pregnancy is a potentially life-threatening condition occurring in 1-2 % of all pregnancies. The most common ectopic implantation site is the fallopian tube, though 10 % of ectopic pregnancies implant in the cervix, ovary, myometrium, interstitial portion of the fallopian tube, abdominal cavity or within a cesarean section scar.FindingsDiagnosis involves a combination of clinical symptoms, serology, and ultrasound. Medical management is a safe and effective option in most clinically stable patients. Patients who have failed medical management, are ineligible, or present with ruptured ectopic pregnancy or heterotopic pregnancy are most often managed with excision by laparoscopy or, less commonly, laparotomy. Management of nontubal ectopic pregnancies may involve medical or surgical treatment, or a combination, as dictated by ectopic pregnancy location and the patient's clinical stability. Following tubal ectopic pregnancy, the rate of subsequent intrauterine pregnancy is high and independent of treatment modality.ConclusionThis review describes the incidence, risk factors, diagnosis, and management of tubal and non-tubal ectopic and heterotopic pregnancies, and reviews the existing data regarding recurrence and future fertility.
Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding, Distress, and Relationship With Physician Among Patients With Advanced Cancer
Authors: Enzinger Andrea C. , Zhang Baohui , Schrag Deborah , Prigerson Holly G. 
Published: October 2015

Purpose To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer. Patients and Methods This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after ≥ one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences. Results Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses. Conclusion Prognostic disclosures are associated with more realistic patient expectations of LE, without decrements to their emotional well-being or the patient-physician relationship.
Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastasis
Authors: Johung Kimberly L. , Yeh Norman , Desai Neil B. , Williams Terence M. , Lautenschlaeger Tim , Arvold Nils D. , Ning Matthew S. , Attia Albert , Lovly Christine M. , Goldberg Sarah , Beal Kathryn , Yu James B. , Kavanagh Brian D. , Chiang Veronica L. , Camidge D. Ross , Contessa Joseph N. 
Published: October 2015

Purpose We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non–small-cell lung cancer (NSCLC) and brain metastasis. Patients and Methods A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling. Results Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P = .633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P < .001). Conclusion Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease.
Routine Imaging for Diffuse Large B-Cell Lymphoma in First Complete Remission Does Not Improve Post-Treatment Survival: A Danish–Swedish Population-Based Study
Authors: El-Galaly Tarec Christoffer , Jakobsen Lasse Hjort , Hutchings Martin , de Nully Brown Peter , Nilsson-Ehle Herman , Székely Elisabeth , Mylam Karen Juul , Hjalmar Viktoria , Johnsen Hans Erik , Bøgsted Martin , Jerkeman Mats 
Published: October 2015

Purpose Routine imaging for diffuse large B-cell lymphoma (DLBCL) in first complete remission (CR) is controversial and plays a limited role in detecting relapse. This population-based study compared the survival of Danish and Swedish patients with DLBCL for whom traditions for routine imaging have been different. Patients and Methods Patients from the Danish and Swedish lymphoma registries were included according to the following criteria: newly diagnosed DLBCL from 2007 to 2012, age 18 to 65 years, and CR after R-CHOP/CHOEP. Follow-up for Swedish patients included symptom assessment, clinical examinations, and blood tests at 3- to 4-month intervals for 2 years, with longer intervals later in follow-up. Imaging was only recommended when relapse was clinically suspected. Follow-up for Danish patients was similar but included routine imaging (usually computed tomography every 6 months for 2 years). Results Danish (n = 525) and Swedish (n = 696) patients with DLBCL had comparable baseline characteristics. Cumulative 2-year progression rate after CR was 6% (95% CI, 4 to 9) for International Prognostic Index (IPI) ≤ 2 versus 21% (95% CI, 13 to 28) for IPI > 2. Age > 60 years (hazard ratio [HR], 2.3; 95% CI, 1.6 to 3.4), elevated lactate dehydrogenase (HR, 2.3; 95% CI, 1.4 to 3.8), B symptoms (HR, 1.7; 95% CI, 1.1 to 2.5), and Eastern Cooperative Oncology Group performance status ≥ 2 (HR, 1.8; 95% CI, 1.0 to 3.0) were associated with worse post-CR survival. Imaging-based follow-up strategy had no impact on survival, neither for all patients nor for IPI-specific subgroups. Conclusion DLBCL relapse after first CR is infrequent, and the widespread use of routine imaging in Denmark did not translate into better survival. This favors follow-up without routine imaging and, more generally, a shift of focus from relapse detection to improved survivorship.
Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti–Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015
Authors: Allegra Carmen J. , Rumble R. Bryan , Hamilton Stanley R. , Mangu Pamela B. , Roach Nancy , Hantel Alexander , Schilsky Richard L. 
Published: October 2015

Purpose An American Society of Clinical Oncology Provisional Clinical Opinion (PCO) offers timely clinical direction after publication or presentation of potentially practice-changing data from major studies. This PCO update addresses the utility of extended RAS gene mutation testing in patients with metastatic colorectal cancer (mCRC) to detect resistance to anti–epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy. Clinical Context Recent results from phase II and III clinical trials in mCRC demonstrate that patients whose tumors harbor RAS mutations in exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146) are unlikely to benefit from therapy with MoAbs directed against EGFR, when used as monotherapy or combined with chemotherapy. Recent Data In addition to the evidence reviewed in the original PCO, 11 systematic reviews with meta-analyses, two retrospective analyses, and two health technology assessments based on a systematic review were obtained. These evaluated the outcomes for patients with mCRC with no mutation detected or presence of mutation in additional exons in KRAS and NRAS. PCO All patients with mCRC who are candidates for anti-EGFR antibody therapy should have their tumor tested in a Clinical Laboratory Improvement Amendments–certified laboratory for mutations in both KRAS and NRAS exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146). The weight of current evidence indicates that anti-EGFR MoAb therapy should only be considered for treatment of patients whose tumor is determined to not have mutations detected after such extended RAS testing.
Structural and Functional Evidence for Testosterone Activation of GPRC6A in Peripheral Tissues
Authors: Pi Min , Kapoor Karan , Wu Yunpeng , Ye Ruisong , Senogles Susan E. , Nishimoto Satoru K. , Hwang Dong-Jin , Miller Duane D. , Narayanan Ramesh , Smith Jeremy C. , Baudry Jerome , Quarles L. Darryl 
Published: October 2015

AbstractG protein-coupled receptor (GPCR) family C group 6 member A (GPRC6A) is a multiligand GPCR that is activated by cations, L-amino acids, and osteocalcin. GPRC6A plays an important role in the regulation of testosterone (T) production and energy metabolism in mice. T has rapid, transcription-independent (nongenomic) effects that are mediated by a putative GPCR. We previously found that T can activate GPRC6A in vitro, but the possibility that T is a ligand for GPRC6A remains controversial. Here, we demonstrate direct T binding to GPRC6A and construct computational structural models of GPRC6A that are used to identify potential binding poses of T. Mutations of the predicted binding site residues were experimentally found to block T activation of GPRC6A, in agreement with the modeling. Using Gpr6ca−/− mice, we confirmed that loss of GPRC6A resulted in loss of T rapid signaling responses and elucidated several biological functions regulated by GPRC6A-dependent T rapid signaling, including T stimulation of insulin secretion in pancreatic islets and enzyme expression involved in the biosynthesis of T in Leydig cells. Finally, we identified a stereo-specific effect of an R-isomer of a selective androgen receptor modulator that is predicted to bind to and shown to activate GPRC6A but not androgen receptor. Together, our data show that GPRC6A directly mediates the rapid signaling response to T and uncovers previously unrecognized endocrine networks.
Relationship between the Bowl-Shaped Geometry of Phosphangulene and an Axial Group on the Phosphorus Atom
Authors: Yamamura Masaki , Nabeshima Tatsuya 
Published: October 2015

Abstract
Phosphangulene derivatives having various substituents on the phosphorus atom, which featured a bowl geometry and restrained bond angle, were synthesized in order to shed light on the relationship between the bowl geometry and the substituent. X-ray analysis revealed that the bowl geometry is significantly dependent on the axial group. An NBO analysis suggested that the bowl geometries become deep as the s-orbital character of the phosphorus orbital in the P–X bonds increases. The NMR, IR, CV, and DFT showed the large s-character in the P–X bonds of the phosphangulene lone pair.
Lipids contribute to epigenetic control via chromatin structure and functions
Authors: Zhdanov Renad , Schirmer Eric C. , Venkatasubramani Anuroop V. , Kerr Alastair R. W. , Mandrou Elena , Rodriguez-Blanco Giovanny , Kagansky Alexander 
Published: October 2015

Abstract
Isolated cases of experimental evidence over the last few decades have shown that, where specifically tested, both prokaryotes and eukaryotes have specific lipid molecules bound to nucleoproteins of the genome. In vitro, some of these lipids exhibit stoichiometric association with DNA polynucleotides with differential affinities toward certain secondary and tertiary structures. Hydrophobic interactions with inner nuclear membrane could provide attractive anchor points for lipid-modified nucleoproteins in organizing the dynamic genome and accordingly there are precedents for covalent bonds between lipids and core histones and, under certain conditions, even DNA. Advances in biophysics, functional genomics, and proteomics in recent years brought about the first sparks of light that promises to uncover some coherent new level of the epigenetic code governed by certain types of lipid–lipid, DNA–lipid, and protein–lipid interactions among other biochemical lipid transactions in the nucleus. Here, we review some of the older and more recent findings and speculate on how critical nuclear lipid transactions are for individual cells, tissues, and organisms.
Time-dependent Dirichlet conditions in finite element discretizations
Authors: Benner Peter , Heiland Jan 
Published: October 2015

Abstract
For the modeling and numerical approximation of problems with time-dependent Dirichlet boundary conditions, one can call on several consistent and inconsistent approaches. We show that spatially discretized boundary control problems can be brought into a standard state space form accessible for standard optimization and model reduction techniques. We discuss several methods that base on standard finite element discretizations, propose a newly developed problem formulation, and investigate their performance in numerical examples. We illustrate that penalty schemes require a wise choice of the penalization parameters in particular for iterative solves of the algebraic equations. Incidentally, we confirm that standard finite element discretizations of higher order may not achieve the optimal order of convergence in the treatment of boundary forcing problems and that convergence estimates by the common method of manufactured solutions can be misleading.