bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barriers and facilitators of access to first-trimester abortion services for women in the developed world: a systematic review
Authors: Doran Frances , Nancarrow Susan 
Published: June 2015

ObjectivesTo identify the barriers and facilitators to accessing first-trimester abortion services for women in the developed world.MethodsSystematic review of published literature. CINAHL, PubMed, Proquest, MEDLINE, InformIT, Scopus, PsycINFO and Academic Search Premier were searched for papers written in the English language, from the developed world, including quantitative and qualitative articles published between 1993 and 2014.ResultsThe search initially yielded 2511 articles. After screening of title, abstract and removing duplicates, 38 articles were reviewed. From the provider perspective, barriers included moral opposition to abortion, lack of training, too few physicians, staff harassment, and insufficient hospital resources, particularly in rural areas. From the women's perspective, barriers included lack of access to services (including distance and lack of service availability), negative attitudes of staff, and the associated costs of the abortion procedure. Service access could be enhanced by increasing training, particularly for mid-level practitioners; by increasing the range of service options, including the use of telehealth; and by creating clear guidelines and referral procedures to alternative providers when staff have a moral opposition to abortion.ConclusionDespite fewer legal barriers to accessing abortion services, the evidence from this review suggests that women in developed countries still face significant inequities in terms of the level of quality and access to services as recommended by the World Health Organization.
Detection of clinically manifest and silent synovitis in the hands and wrists by fluorescence optical imaging
Authors: Kisten Yogan , Györi Noémi , af Klint Erik , Rezaei Hamed , Levitsky Adrian , Karlsson Anna , van Vollenhoven Ronald 
Published: June 2015

ObjectivesThe correct identification of synovitis is critical for achieving optimal therapy results. Fluorescence optical imaging (FOI) is a novel modality based on the use of an intravenous fluorophore, which enables fluorescent imaging of the hands and wrists with increased focal optical signal intensities in areas of high perfusion and/or capillary leakage. The study objective was to determine the diagnostic utility of FOI in detecting apparent and clinically non-apparent active synovitis.MethodsBilateral hand and wrist joints (n=872) of 26 patients with inflammatory arthritis assessed by standard clinical examination, musculoskeletal ultrasound (MSUS) and FOI were studied. Synovitis was defined as tender and swollen joints on clinical examination, presence of synovial thickening and intra-articular Doppler signals on MSUS, and abnormal focal optical signal intensities on FOI, respectively. Subclinical synovitis was defined as being clinically non-apparent, but positively inflamed on MSUS.ResultsDepending on the standard used to define inflammation, FOI ranged from 73–83% sensitive and 83–95% specific for detecting manifest synovitis. For detecting clinically silent synovitis, the sensitivity, specificity and positive and negative predictive values of FOI were 80%, 96%, 77% and 97%, respectively.ConclusionsThe high degree of agreement between MSUS and FOI suggest its use in clinical practice, especially when MSUS is not available, in order to identify synovitis earlier and with greater confidence. FOI may be particularly useful in identifying patients with clinically non-apparent joint inflammation of the hands and/or wrists.
On the L2-Poincaré duality for incomplete Riemannian manifolds: A general construction with applications
Authors: Bei Francesco 
Published: June 2015

Let [Formula: see text] be an open, oriented and incomplete Riemannian manifold of dimension [Formula: see text]. Under some general conditions we show the existence of a Hilbert complex [Formula: see text] such that its cohomology groups, labeled with [Formula: see text], satisfy the following properties: [Formula: see text] [Formula: see text] (Poincaré duality holds) There exists a well-defined and nondegenerate pairing: [Formula: see text] If [Formula: see text] is a Fredholm complex, then every closed extension of the de Rham complex [Formula: see text] is a Fredholm complex and, for each [Formula: see text], the quotient [Formula: see text] is a finite dimensional vector space.
Novel Cancer Therapeutics with Allosteric Modulation of the Mitochondrial C-Raf–DAPK Complex by Raf Inhibitor Combination Therapy
Authors: Tsai Yi-Ta , Chuang Mei-Jen , Tang Shou-Hung , Wu Sheng-Tang , Chen Yu-Chi , Sun Guang-Huan , Hsiao Pei-Wen , Huang Shih-Ming , Lee Hwei-Jen , Yu Cheng-Ping , Ho Jar-Yi , Lin Hui-Kuan , Chen Ming-Rong , Lin Chung-Chih , Chang Sun-Yran , Lin Victor C. , Yu Dah-Shyong , Cha Tai-Lung 
Published: June 2015

Abstract
Mitochondria are the powerhouses of cells. Mitochondrial C-Raf is a potential cancer therapeutic target, as it regulates mitochondrial function and is localized to the mitochondria by its N-terminal domain. However, Raf inhibitor monotherapy can induce S338 phosphorylation of C-Raf (pC-RafS338) and impede therapy. This study identified the interaction of C-Raf with S308 phosphorylated DAPK (pDAPKS308), which together became colocalized in the mitochondria to facilitate mitochondrial remodeling. Combined use of the Raf inhibitors sorafenib and GW5074 had synergistic anticancer effects in vitro and in vivo, but targeted mitochondrial function, rather than the canonical Raf signaling pathway. C-Raf depletion in knockout MEFC-Raf−/− or siRNA knockdown ACHN renal cancer cells abrogated the cytotoxicity of combination therapy. Crystal structure simulation showed that GW5074 bound to C-Raf and induced a C-Raf conformational change that enhanced sorafenib-binding affinity. In the presence of pDAPKS308, this drug–target interaction compromised the mitochondrial targeting effect of the N-terminal domain of C-Raf, which induced two-hit damages to cancer cells. First, combination therapy facilitated pC-RafS338 and pDAPKS308 translocation from mitochondria to cytoplasm, leading to mitochondrial dysfunction and reactive oxygen species (ROS) generation. Second, ROS facilitated PP2A-mediated dephosphorylation of pDAPKS308 to DAPK. PP2A then dissociated from the C-Raf–DAPK complex and induced profound cancer cell death. Increased pDAPKS308 modification was also observed in renal cancer tissues, which correlated with poor disease-free survival and poor overall survival in renal cancer patients. Besides mediating the anticancer effect, pDAPKS308 may serve as a predictive biomarker for Raf inhibitors combination therapy, suggesting an ideal preclinical model that is worthy of clinical translation. Cancer Res; 75(17); 3568–82. ©2015 AACR.
Tumor-Specific Effector CD8+ T Cells That Can Establish Immunological Memory in Humans after Adoptive Transfer Are Marked by Expression of IL7 Receptor and c-myc
Authors: Chandran Smita S. , Paria Biman C. , Srivastava Abhishek K. , Rothermel Luke D. , Stephens Daniel J. , Kammula Udai S. 
Published: June 2015

Abstract
The optimal T-cell attributes for adoptive cancer immunotherapy are unclear. Recent clinical trials of ex vivo–expanded tumor-infiltrating lymphocytes indicated that differentiated T effector cells can elicit durable antitumor responses in some patients with cancer, with their antitumor activity tightly correlated with their persistence in the host. Thus, there is great interest in the definition of intrinsic biomarkers that can predict the conversion of short-lived tumor antigen–specific T effector cells into long-lived T memory cells. Long-term persistence of ex vivo–expanded tumor-specific CD8+ T effector clones has been reported in refractory metastatic melanoma patients after adoptive T-cell transfer. By using highly homogeneous clone populations from these preparations, we performed a comparative transcriptional profiling to define preinfusion molecular attributes that can be ascribed to an effector-to-memory transition. Through this route, we discovered that preinfusion T-cell clones that expressed the IL7 receptor (IL7R) and c-myc were more likely to persist longer after adoptive transfer to patients. The predictive value of these two biomarkers was strengthened by using IL7R protein, IL7-induced pSTAT5, and c-myc mRNA expression to prospectively identify human tumor-specific T effector clones capable of engraftment into immunodeficient mice. Overall, our findings reveal IL7R and c-myc expression as intrinsic biomarkers that can predict the fate of CD8+ T effector cells after adoptive transfer. Cancer Res; 75(16); 3216–26. ©2015 AACR.
Impact of Short-term 1,25-Dihydroxyvitamin D3 on the Chemopreventive Efficacy of Erlotinib against Oral Cancer
Authors: Bothwell Katelyn D. , Shaurova Tatiana , Merzianu Mihai , Suresh Amritha , Kuriakose Moni A. , Johnson Candace S. , Hershberger Pamela A. , Seshadri Mukund 
Published: June 2015

Abstract
Activation of the epidermal growth factor receptor (EGFR) pathway is an early event in head and neck carcinogenesis. As a result, targeting EGFR for chemoprevention of head and neck squamous cell carcinomas (HNSCC) has received considerable attention. In the present study, we examined the impact of 1,25(OH)2D3, the active metabolite of the nutritional supplement vitamin D on the chemopreventive efficacy of the EGFR inhibitor, erlotinib, against HNSCC. Experimental studies were conducted in patient-derived xenografts (PDX) and the 4-nitroquinoline-1-oxide (4NQO) carcinogen-induced model of HNSCC. Short-term treatment (4 weeks) of PDX-bearing mice with 1,25(OH)2D3 and erlotinib resulted in significant inhibition of tumor growth. Noninvasive MRI enabled longitudinal monitoring of disease progression in the 4NQO model with 100% of control animals showing evidence of neoplastic lesions by 24 weeks. Among the experimental groups, animals treated with the combination regimen showed the greatest reduction in tumor incidence and volume (P &lt; 0.05). Combination treatment was well tolerated and was not associated with any significant change in body weight. Histopathologic assessment revealed a significant reduction in the degree of dysplasia with combination treatment. Immunoblot analysis of whole tongue extracts showed downregulation of phospho-EGFR and phospho-Akt with the combination regimen. These results highlight the potential of 1,25(OH)2D3 to augment the efficacy of erlotinib against HNSCC. Further optimization of schedule and sequence of this combination regimen along with investigation into the activity of less calcemic analogues or dietary vitamin D is essential to fully realize the potential of this approach. Cancer Prev Res; 8(9); 765–76. ©2015 AACR.
Pregnancy in Women With a Mechanical Heart Valve
Authors: van Hagen Iris M. , Roos-Hesselink Jolien W. , Ruys Titia P.E. , Merz Waltraut M. , Goland Sorel , Gabriel Harald , Lelonek Malgorzata , Trojnarska Olga , Al Mahmeed Wael Abdulrahman , Balint Hajnalka Olga , Ashour Zeinab , Baumgartner Helmut , Boersma Eric , Johnson Mark R. , Hall Roger 
Published: June 2015

Background—
Pregnant women with a mechanical heart valve (MHV) are at a heightened risk of a thrombotic event, and their absolute need for adequate anticoagulation puts them at considerable risk of bleeding and, with some anticoagulants, fetotoxicity.

Methods and Results—

Within the prospective, observational, contemporary, worldwide Registry of Pregnancy and Cardiac disease (ROPAC), we describe the pregnancy outcome of 212 patients with an MHV. We compare them with 134 patients with a tissue heart valve and 2620 other patients without a prosthetic valve. Maternal mortality occurred in 1.4% of the patients with an MHV, in 1.5% of patients with a tissue heart valve (
P
=1.000), and in 0.2% of patients without a prosthetic valve (
P
=0.025). Mechanical valve thrombosis complicated pregnancy in 10 patients with an MHV (4.7%). In 5 of these patients, the valve thrombosis occurred in the first trimester, and all 5 patients had been switched to some form of heparin. Hemorrhagic events occurred in 23.1% of patients with an MHV, in 5.1% of patients with a tissue heart valve (
P
<0.001), and in 4.9% of patients without a prosthetic valve (
P
<0.001). Only 58% of the patients with an MHV had a pregnancy free of serious adverse events compared with 79% of patients with a tissue heart valve (
P
<0.001) and 78% of patients without a prosthetic valve (
P
<0.001). Vitamin K antagonist use in the first trimester compared with heparin was associated with a higher rate of miscarriage (28.6% versus 9.2%;
P
<0.001) and late fetal death (7.1% versus 0.7%;
P
=0.016).

Conclusions—
Women with an MHV have only a 58% chance of experiencing an uncomplicated pregnancy with a live birth. The markedly increased mortality and morbidity warrant extensive prepregnancy counseling and centralization of care.
Dopamine and Consolidation of Episodic Memory: Timing Is Everything
Authors: Grogan John , Bogacz Rafal , Tsivos Demitra , Whone Alan , Coulthard Elizabeth 
Published: June 2015

Abstract
Memory consolidation underpins adaptive behavior and dopaminergic networks may be critical for prolonged, selective information storage. To understand the time course of the dopaminergic contribution to memory consolidation in humans, here we investigate the effect of dopaminergic medication on recall and recognition in the short and longer term in Parkinson disease (PD). Fifteen people with PD were each tested on or off dopaminergic medication during learning/early consolidation (Day 1) and/or late consolidation (Day 2). Fifteen age-matched healthy participants were tested only once. On Day 1 participants learned new information, and early episodic memory was tested after 30 min. Then on Day 2, recall and recognition were retested after a 24-hr delay. Participants on medication on Day 1 recalled less information at 30 min and 24 hr. In contrast, patients on medication on Day 2 (8–24 hr after learning) recalled more information at 24 hr than those off medication. Although recognition sensitivity was unaffected by medication, response bias was dependent on dopaminergic state: Medication during learning induced a more liberal bias 24 hr later, whereas patients off medication during learning were more conservative responders 24 hr later. We use computational modeling to propose possible mechanisms for this change in response bias. In summary, dopaminergic medication in PD patients during learning impairs early consolidation of episodic memory and makes delayed responses more liberal, but enhances late memory consolidation presumably through a dopamine-dependent consolidation pathway that may be active during sleep.
Stakeholder Perspectives on the Attribution of Extreme Weather Events: An Explorative Enquiry
Authors: Sippel Sebastian , Walton Peter , Otto Friederike E. L. 
Published: June 2015

Abstract
Recent extreme weather events and their impacts on societies have highlighted the need for timely adaptation to the changing odds of their occurrence. Such measures require appropriate information about likely changes in event frequency and magnitude on relevant spatiotemporal scales. However, to support robust climate information for decision-making, an effective communication between scientists and stakeholders is crucial. In this context, weather event attribution studies are increasingly raising attention beyond academic circles, although the understanding of how to take it beyond academia is still evolving. This paper presents the results of a study that involved in-depth interviews with stakeholders from a range of sectors about potential applications and the general usefulness of event attribution studies. A case study of the hot and dry summer 2012 in southeast Europe is used as a concrete example, with a focus on the applicability of attribution results across sectors. An analysis of the interviews reveals an abundant interest among the interviewed stakeholders and highlights the need for information on the causes and odds of extreme events, in particular on regional scales. From this data key aspects of stakeholder engagement are emerging, which could productively feed back into how probabilistic event attribution studies are designed and communicated to ensure practical relevance and usefulness for the stakeholder community.
Predictors of success following endovascular retreatment of intracranial aneurysms
Authors: Mascitelli Justin R , Oermann Eric K , Mocco J , Fifi Johanna T , Paramasivam Srinivasan , Stapleton Christopher J , Patel Aman B 
Published: June 2015

Introduction Although approximately one in every 10 patients undergoing coil embolization of intracranial aneurysms requires retreatment, the factors that are associated with outcome following retreatment remain to be fully elucidated. Methods This is a single-center, retrospective review of 43 patients with 58 intracranial aneurysms that were retreated from 2004 to 2014. Aneurysms undergoing first time or microsurgical retreatment were excluded. Retreatment types were grouped into those without permanent parent vessel support (stand-alone and balloon-assisted coiling) versus those with permanent parent vessel support (stent-assisted coiling, stand-alone stenting, and flow diversion). The Modified Raymond Roy Classification was used to group aneurysms at all angiographic follow-up points either in the successful outcome group (Class I or II) or the unsuccessful outcome group (Class IIIa or IIIb). Results Of aneurysms with follow-up, 50% were in the successful group and 50% in the unsuccessful group. In univariate analysis, small aneurysm size ( p < 0.001), previous treatment type ( p = 0.022), retreatment type ( p = 0.001), and initial occlusion class ( p = 0.005) were all associated with angiographic outcome. In multivariate analysis, small aneurysm size ( p = 0.005, odds ratio (OR) 24.56, confidence interval (CI) 2.68–225.4) and retreatment type with permanent parent vessel support, namely stent-assisted coiling ( p = 0.017, OR 31.1, CI 1.89–517.7), were associated with retreatment success. Conclusions Small aneurysm size and retreatment with permanent parent vessel support, namely stent-assisted coiling, are predictors of success following endovascular retreatment of intracranial aneurysms. These findings could be useful in the effort to both prevent and predict treatment failure following endovascular retreatment.
Permanent endovascular balloon occlusion of the vertebral artery as an adjunct to the surgical resection of selected cervical spine tumors: A single center experience
Authors: Ogungbemi Ayokunle , Elwell Vivien , Choi David , Robertson Fergus 
Published: June 2015

Background and purpose Complete surgical resection of cervical spine tumors is often challenging when there is tumor encasement of major neck vessels. Pre-operative endovascular sacrifice of the major vessels can facilitate safe tumor resection. The use of transarterial detachable coils has been described in this setting, but it can be time-consuming and costly to occlude a patent parent vessel using this method. Our aim was to evaluate the safety and effectiveness of our endovascular detachable balloon occlusion technique, performed without prior balloon test occlusion in the pre-operative management of these tumors. Methods We retrospectively reviewed 18 consecutive patients undergoing pre-operative unilateral permanent endovascular balloon occlusion of tumor-encased vertebral arteries in our institution. Procedure-related ischemic or thromboembolic complication was defined as focal neurologic deficit attributable to the endovascular occlusion which occurs before subsequent surgical resection. Results Successful pre-operative endovascular vertebral artery sacrifice using detachable balloons was achieved in 100% ( n = 18) of cases without prior balloon test occlusion. Procedural complication rate was 5.6% as one patient developed transient focal neurology secondary to a delayed cerebellar infarct at home on day 11 and subsequently made a full recovery. There were no cases of distal balloon migration. Complete macroscopic resection of tumor as reported by the operating surgeon was achieved in 89% of cases. Conclusion Pre-operative endovascular sacrifice of the vertebral artery using detachable balloons and without prior balloon test occlusion is a safe procedure with low complication rates and good surgeon reported rates of total resection.
Exosomes released by chronic lymphocytic leukemia cells induce the transition of stromal cells into cancer-associated fibroblasts
Authors: Paggetti Jerome , Haderk Franziska , Seiffert Martina , Janji Bassam , Distler Ute , Ammerlaan Wim , Kim Yeoun Jin , Adam Julien , Lichter Peter , Solary Eric , Berchem Guy , Moussay Etienne 
Published: June 2015

Key PointsCLL-derived exosomes are internalized by stromal cells, deliver functional microRNA and proteins, and activate key signaling pathways. Stromal cells exposed to CLL-derived exosomes demonstrate a CAF-like phenotype and secrete factors promoting CLL cell survival.
Reactivity of rat bone marrow-derived macrophages to neurotransmitter stimulation in the context of collagen II-induced arthritis
Authors: Muschter Dominique , Göttl Claudia , Vogel Mandy , Grifka Joachim , Straub Rainer H. , Grässel Susanne 
Published: June 2015

Abstract
Introduction
Numerous observations indicate that rheumatoid arthritis (RA) has a bone marrow component. In parallel, local synovial changes depend on neuronal components of the peripheral sympathetic nervous system. Here, we wanted to analyze whether collagen II-induced arthritis (CIA) has an impact on number, adhesion, apoptosis, and proliferation of the macrophage subset of bone marrow cells and how alterations in neurotransmitter microenvironment affect these properties.

Methods
Bone marrow-derived macrophages (BMMs) were isolated from Dark Agouti rats at different stages of CIA, and number, adhesion, caspase 3/7 activity, and proliferation were analyzed in the presence of acetylcholine (ACh), noradrenaline (NA), and vasoactive intestinal peptide (VIP).

Results
Opposed to enhanced CD11b+ (cluster of differentiation 11b-positive) and EMR1+ (epidermal growth factor-like module-containing mucin-like hormone receptor-like 1-positive) cells, characterizing the macrophage subset, in native bone marrow of rats with acute inflammatory arthritis, we found decreased numbers of CIA macrophages after enrichment and culture in comparison with healthy (control) animals. Adhesion studies revealed significantly reduced attachment to plastic in acute arthritis and collagen type I and fibronectin in chronic arthritis. Additionally, we found a strong reduction in proliferation of BMMs at CIA onset and in the chronic phase of CIA. Apoptosis remained unaffected. Neurotransmitter stimulation profoundly affected proliferation, adhesion, and apoptosis of BMMs from CIA and control rats, depending on disease time point. Cultured BMMs from CIA and control animals expressed neurotransmitter receptors for ACh, VIP and NA, but the expression profile seemed not to be affected by CIA.

Conclusions
Induction of CIA distinctly inhibits proliferation of BMMs in low- and non-inflammatory phases and reduces attachment to plastic at the acute inflammatory arthritis stage and adhesion to collagen I and fibronectin at the chronic stage. Influence of neurotransmitter stimulation on adhesion, apoptosis, and proliferation is altered by CIA depending on disease stage. We suggest an altered reactivity of BMMs to neurotransmitter stimulation caused by CIA and maybe also by aging.