bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of physical activity and fitness in class II and III obese individuals: a systematic review
Authors: Baillot A. , Audet M. , Baillargeon J. P. , Dionne I. J. , Valiquette L. , Rosa‐Fortin M. M. , Abou Chakra C. N. , Comeau É. , Langlois M. F. 
Published: April 2014

SummaryThe objective of this systematic review was to appraise current knowledge on the impact of physical activity (PA) and physical fitness (PF) on the health of class II and III obese subjects and bariatric surgery (BS) patients. All original studies were searched using four databases (Medline®, Scopus®, CINAHL and Sportdiscus). Two independent investigators selected studies assessing the impact of PA or PF on specific health outcomes (anthropometric parameters, body composition, cardiometabolic risk factors, PF, wellness) in adults with a body mass index ≥35 kg m−2 or in BS patients. Conclusions were drawn based on a rating system of evidence. From 3,170 papers identified, 40 papers met the inclusion criteria. The vast majority of studies were recently carried out with a predominance of women. Less than one‐third of these studies were experimental and only three of them were of high quality. Each study reported at least one beneficial effect of PA or PF. However, a lack of high‐quality studies and heterogeneity in designs prevented us from finding high levels of evidence. In conclusion, although results support the importance of PA and PF to improve the health of this population, higher‐quality trials are required to strengthen evidence‐based recommendations.
Alemtuzumab with corticosteroid minimization for pediatric deceased donor renal transplantation: A seven‐yr experience
Authors: Supe‐Markovina Katarina , Melquist Jonathan J. , Connolly Deirdre , DiCarlo Heather N. , Waltzer Wayne C. , Fine Richard N. , Darras Frank S. 
Published: April 2014

AbstractAlemtuzumab is a monoclonal antibody targeting CD52 receptors on B and T lymphocytes and is an effective induction agent in pediatric renal transplantation. We report a seven‐yr experience using alemtuzumab induction and steroid‐free protocol in the pediatric population as safe and effective. Twenty‐one pediatric deceased donor renal transplants were performed at a single academic institution. All received induction with single‐dose alemtuzumab and were maintained on a steroid‐free protocol using TAC and MMF immunosuppression. There were 15 males and six females in the study whose ages ranged from one to 19 yr. The average follow‐up was 32 months (range from 12 to 78.2 months and median 33.7 ± 23.7 months). All patients had immediate graft function. Graft survival was 95%, and patient survival was 100%. Mean 12 and 36 months eGFR were 63.33 ± 21.01 and 59.90 ± 15.27 mL/min/1.73m2, respectively. Three patients developed acute T‐cell‐mediated rejection due to non‐adherence while no recipients developed cytomegalovirus infection, PTLD, or polyoma BK viral nephropathy. Steroid avoidance with single‐dose alemtuzumab induction provides adequate and safe immunosuppression in pediatric deceased donor renal transplant recipients receiving TAC and low‐dose MMF maintenance therapy.
Extracorporeal Treatment for Tricyclic Antidepressant Poisoning: Recommendations from the EXTRIP Workgroup
Authors: Yates Christopher , Galvao Tais , Sowinski Kevin M. , Mardini Karine , Botnaru Tudor , Gosselin Sophie , Hoffman Robert S. , Nolin Thomas D. , Lavergne Valéry , Ghannoum Marc ,   the EXTRIP workgroup
Published: April 2014

AbstractThe Extracorporeal Treatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, the workgroup presents its results for tricyclic antidepressants (TCAs). After an extensive literature search, using a predefined methodology, the subgroup responsible for this poison reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two‐round modified Delphi method was chosen to reach a consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Blinded votes were compiled, returned, and discussed in person at a meeting. A second vote determined the final recommendations. Seventy‐seven articles met inclusion criteria. Only case reports, case series, and one poor‐quality observational study were identified yielding a very low quality of evidence for all recommendations. Data on 108 patients, including 12 fatalities, were abstracted. The workgroup concluded that TCAs are not dialyzable and made the following recommendation: ECTR is not recommended in severe TCA poisoning (1D). The workgroup considers that poisoned patients with TCAs are not likely to have a clinical benefit from extracorporeal removal and recommends it NOT to be used in TCA poisoning.
Diverse oxyporine rove beetles from the Early Cretaceous of China (Coleoptera: Staphylinidae)
Authors: CAI CHEN‐YANG , HUANG DI‐YING 
Published: April 2014

AbstractTwo new genera and species, Protoxyporus grandis gen. et sp.n. and Cretoxyporus extraneus gen. et sp.n., are described and figured on the basis of two well‐preserved impression fossils from the Lower Cretaceous Yixian Formation of China. The two genera display a combination of traits that are diagnostic of the extant staphylinid subfamily Oxyporinae: large and prominent mandibles, distinctly separated mesocoxae, abdominal tergites III–VII each with a pair of basolateral ridges, and abdominal intersegmental membranes with ‘brick‐wall’ pattern. Protoxyporus differs from extant Oxyporus in retaining the following plesiomorphic features: an elongate intercoxal process (or longitudinal carina) between metacoxae, relatively narrowly separated mesocoxae, less developed metaventral anterior process, and long infraorbital ridges. Cretoxyporus is morphologically very similar to Oxyporus, but retains distinct elongate infraorbital ridges. The discovery of two new oxyporine genera suggests that the early oxyporines were more diverse and their evolutionary history more complicated than previously documented.This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:pub:11503976‐D577‐45D2‐ACCB‐8226782EF817.
On the Nature of Null Clausal Complements in Japanese
Authors: Kasai Hironobu 
Published: April 2014

AbstractThis paper argues that the null clausal complement in Japanese is not derived via CP ellipsis but is rather an instance of pro. The availability of sloppy interpretation in the construction under investigation apparently argues that ellipsis is involved there, but it is revealed under close scrutiny of the sloppy interpretation in question that the null clausal complement behaves like deep anaphora, not like surface anaphora.
Submicroscopic Infections with Plasmodium falciparum during Pregnancy and Their Association with Circulating Cytokine, Chemokine, and Cellular Profiles
Authors: Ibitokou Samad A. , Boström Stéphanie , Brutus Laurent , Tuikue Ndam Nicaise , Vianou Bertin , Agbowaï Carine , Amadoudji Zin Martin , Huynh Bich Tram , Massougbodji Achille , Deloron Philippe , Troye-Blomberg Marita , Fievet Nadine , Luty Adrian J. F. 
Published: April 2014

ABSTRACTThe immunological consequences of pregnancy-associated malaria (PAM) due toPlasmodium falciparumhave been extensively investigated in cross-sectional studies conducted at delivery, but there have been very few longitudinal studies of changes due to PAM during pregnancy. We conducted a prospective study in Benin to investigate the changes associated with PAM in groups of 131 and 111 women at inclusion in the second trimester and at delivery, respectively. Infected women were identified by standard microscopic examinations of blood smears and by quantitative PCR (qPCR) assays and were matched to uninfected control women by age, gestational age, and gravidity. We quantified plasma levels of a panel of soluble immunological mediators and other mediators, as well as the frequencies of peripheral blood mononuclear cell types. Comparisons of these variables in infected and uninfected women used multivariate analyses, and we also assessed the predictive value of variables measured at inclusion for pregnancy outcomes at delivery. In multivariate analyses, peripheral plasma interleukin 10 (IL-10) and gamma interferon-inducible protein 10 (IP-10) levels were associated with PAM at inclusion and at delivery, while higher IL-10 levels distinguished qPCR-detectable submicroscopic infections at inclusion but not at delivery. Maternal anemia at delivery was associated with markers of proinflammatory (increased frequency of monocytes) and anti-inflammatory (increased IL-10 levels and increased activation of regulatory T cells) activity measured at inclusion. Elevated concentrations of IL-10 are associated with the majority ofP. falciparuminfections during pregnancy, but this marker alone does not identify all submicroscopic infections. Reliably identifying such occult infections will require more sensitive and specific methods.
Clinical Evaluation of the Cartridge-Based GeneXpert Human Papillomavirus Assay in Women Referred for Colposcopy
Authors: Einstein Mark H. , Smith Katherine M. , Davis Thomas E. , Schmeler Kathleen M. , Ferris Daron G. , Savage Ashlyn H. , Gray Jermaine E. , Stoler Mark H. , Wright Thomas C. , Ferenczy Alex , Castle Philip E. 
Published: April 2014

ABSTRACT

High-risk human papillomavirus (hrHPV) testing is now being introduced as a potential primary screening test for improved detection of cervical precancer and cancer. Current U.S. Food and Drug Administration-approved tests are batch tests that take several hours to complete. A rapid, non-batch test might permit point-of-care (POC) testing, which can facilitate same-day screen and management strategies. For a non-batch, random-access platform (GeneXpert; Cepheid, Sunnyvale, CA), a prototype hrHPV assay (Xpert) has been developed where testing for 14 hrHPV types can be completed in 1 h. In the first clinical evaluation, Xpert was compared to two validated hrHPV tests, the cobas HPV test (cobas, Roche Molecular Systems) and Hybrid Capture 2 (hc2, Qiagen), and to histologic outcomes using specimens from colposcopy referral populations at 7 clinical sites in the United States (
n
= 697). The sensitivity of Xpert for cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2+) (
n
= 141) was equal to that of cobas (90.8% versus 90.8%,
P
= 1) and greater than that of hc2 (90.8% versus 81.6%,
P
= 0.004). Xpert was more specific than cobas (42.6% versus 39.6%,
P
= 0.02) and less specific than hc2 (42.6% versus 47.7%,
P
< 0.001). Similar results were observed for cervical intraepithelial neoplasia grade 3 or higher (CIN3+) (
n
= 91). HPV16 detection by Xpert identified 41.8% of the CIN2+ specimens with a positive predictive value (PPV) of 54.6%. By comparison, HPV16 detection by cobas identified 42.6% of the CIN2+ specimens with a PPV of 55.0%. hrHPV detection by the Xpert demonstrated excellent clinical performance for identifying women with CIN2+ and CIN3+ that was comparable to that of currently available clinically validated tests.
Viral and Cellular FLICE-Inhibitory Proteins: a Comparison of Their Roles in Regulating Intrinsic Immune Responses
Authors: Shisler Joanna L. 
Published: April 2014

ABSTRACT
FLICE-inhibitory proteins (FLIPs) are a family of viral (poxvirus and herpesvirus) and cellular proteins. The hallmark of this family is the presence of tandem death-effector domains (DEDs). Despite this shared motif, each protein possesses different abilities to modulate apoptosis, NF-κB, and interferon regulatory factor 3 (IRF3). These similarities and differences are discussed and highlighted here. The comparative study of FLIPs provides a unique basis to understand virus-host interactions, viral pathogenesis, and cellular regulation of immune system signal transduction pathways.
Conserved Neutralizing Epitope at Globular Head of Hemagglutinin in H3N2 Influenza Viruses
Authors: Iba Yoshitaka , Fujii Yoshifumi , Ohshima Nobuko , Sumida Tomomi , Kubota-Koketsu Ritsuko , Ikeda Mariko , Wakiyama Motoaki , Shirouzu Mikako , Okada Jun , Okuno Yoshinobu , Kurosawa Yoshikazu , Yokoyama Shigeyuki 
Published: April 2014

ABSTRACT
Neutralizing antibodies that target the hemagglutinin of influenza virus either inhibit binding of hemagglutinin to cellular receptors or prevent the low-pH-induced conformational change in hemagglutinin required for membrane fusion. In general, the former type of antibody binds to the globular head formed by HA1 and has narrow strain specificity, while the latter type binds to the stem mainly formed by HA2 and has broad strain specificity. In the present study, we analyzed the epitope and function of a broadly neutralizing human antibody against H3N2 viruses, F005-126. The crystal structure of F005-126 Fab in complex with hemagglutinin revealed that the antibody binds to the globular head, spans a cleft formed by two hemagglutinin monomers in a hemagglutinin trimer, and cross-links them. It recognizes two peptide portions (sites L and R) and a glycan linked to asparagine at residue 285 using three complementarity-determining regions and framework 3 in the heavy chain. Binding of the antibody to sites L (residues 171 to 173, 239, and 240) and R (residues 91, 92, 270 to 273, 284, and 285) is mediated mainly by van der Waals contacts with the main chains of the peptides in these sites and secondarily by hydrogen bonds with a few side chains of conserved sequences in HA1. Furthermore, the glycan recognized by F005-126 is conserved among H3N2 viruses. F005-126 has the ability to prevent low-pH-induced conformational changes in hemagglutinin. The newly identified conserved epitope, including the glycan, should be immunogenic in humans and may induce production of broadly neutralizing antibodies against H3 viruses.

IMPORTANCE
Antibodies play an important role in protection against influenza virus, and hemagglutinin is the major target for virus neutralizing antibodies. It has long been believed that all effective neutralizing antibodies bind to the surrounding regions of the sialic acid-binding pocket and inhibit the binding of hemagglutinin to the cellular receptor. Since mutations are readily introduced into such epitopes, this type of antibody shows narrow strain specificity. Recently, however, broadly neutralizing antibodies have been isolated. Most of these bind either to conserved sites in the stem region or to the sialic acid-binding pocket itself. In the present study, we identified a new neutralizing epitope in the head region recognized by a broadly neutralizing human antibody against H3N2. This epitope may be useful for design of vaccines.
Reconstruction of the evolution of the Niger River and implications for sediment supply to the Equatorial Atlantic margin of Africa during the Cretaceous and the Cenozoic
Authors: Bonne Kathelijne P. M. 
Published: April 2014

Abstract

This paper presents a reconstruction of the palaeodrainage evolution of the Niger River in West Africa in order to contribute to the understanding of sediment supply to the Niger Delta. It has been covered extensively in literature that the Niger River has undergone changes along its course in the Holocene, as implied by the large bend it makes in Mali. However, other enigmatic bends further downstream are indicative of an older and more complicated history that has yet to be understood, and is the focus of this paper. Until now, sediment supply from the Niger River has been considered as being negligible compared to that of the Benue River. The results of this study imply that the contribution from the Niger River was more important than previously thought. The Niger River obtained its present-day geometry in three phases: a Bida Basin phase (Maastrichtian–Miocene); a Iullemmeden Basin phase (Miocene–Pleistocene); and a present-day Niger River phase (Holocene). In the Miocene, an important capture event occurred, increasing the incipient drainage basin by 10
6
km
2
, thereby changing the provenance of the sediment supplied to the Niger Delta from mainly crystalline basement to mixed lithologies including sandstone, shale, limestone and volcanic outcrops.
Impaired JNK Signaling Cooperates with KrasG12D Expression to Accelerate Pancreatic Ductal Adenocarcinoma
Authors: Davies Clare C. , Harvey Emma , McMahon Raymond F.T. , Finegan Katherine G. , Connor Frances , Davis Roger J. , Tuveson David A. , Tournier Cathy 
Published: April 2014

Abstract
The c-Jun N-terminal protein kinase (JNK) and its two direct activators, namely the mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) and MKK7, constitute a signaling node frequently mutated in human pancreatic ductal adenocarcinoma (PDAC). Here we demonstrate the cooperative interaction of endogenous expression of KrasG12D with loss-of-function mutations in mkk4 or both, mkk4 and mkk7 genes in the pancreas. More specifically, impaired JNK signaling in a subpopulation of Pdx1-expressing cells dramatically accelerated the appearance of KrasG12D-induced acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasias, which rapidly progressed to invasive PDAC within 10 weeks of age. Furthermore, inactivation of mkk4/mkk7 compromised acinar regeneration following acute inflammatory stress by locking damaged exocrine cells in a permanently de-differentiated state. Therefore, we propose that JNK signaling exerts its tumor suppressive function in the pancreas by antagonizing the metaplastic conversion of acinar cells toward a ductal fate capable of responding to oncogenic stimulation. Cancer Res; 74(12); 3344–56. ©2014 AACR.
Cancer Cell Lines for Drug Discovery and Development
Authors: Wilding Jennifer L. , Bodmer Walter F. 
Published: April 2014

Abstract
Despite the millions of dollars spent on target validation and drug optimization in preclinical models, most therapies still fail in phase III clinical trials. Our current model systems, or the way we interpret data from them, clearly do not have sufficient clinical predictive power. Current opinion suggests that this is because the cell lines and xenografts that are commonly used are inadequate models that do not effectively mimic and predict human responses. This has become such a widespread belief that it approaches dogma in the field of drug discovery and optimization and has spurred a surge in studies devoted to the development of more sophisticated animal models such as orthotopic patient-derived xenografts in an attempt to obtain more accurate estimates of whether particular cancers will respond to given treatments. Here, we explore the evidence that has led to the move away from the use of in vitro cell lines and toward various forms of xenograft models for drug screening and development. We review some of the pros and cons of each model and give an overview of ways in which the use of cell lines could be modified to improve the predictive capacity of this well-defined model. Cancer Res; 74(9); 2377–84. ©2014 AACR.
Expression Signature Defined byFOXM1–CCNB1Activation Predicts Disease Recurrence in Non–Muscle-Invasive Bladder Cancer
Authors: Kim Seon-Kyu , Roh Yun-Gil , Park Kiejung , Kang Tae-Hong , Kim Wun-Jae , Lee Ju-Seog , Leem Sun-Hee , Chu In-Sun 
Published: April 2014

AbstractPurpose: Although standard treatment with transurethral resection and intravesical therapy (IVT) is known to be effective to address the clinical behavior of non–muscle-invasive bladder cancer (NMIBC), many patients fail to respond to the treatment and frequently experience disease recurrence. Here, we aim to identify a prognostic molecular signature that predicts the NMIBC heterogeneity and response to IVT.Experimental Design: We analyzed the genomic profiles of 102 patients with NMIBC to identify a signature associated with disease recurrence. The validity of the signature was verified in three independent patient cohorts (n = 658). Various statistical methods, including a leave-one-out cross-validation and multivariate Cox regression analyses, were applied to identify a signature. We confirmed an association between the signature and tumor aggressiveness with experimental assays using bladder cancer cell lines.Results: Gene expression profiling in 102 patients with NMIBC identified a CCNB1 signature associated with disease recurrence, which was validated in another three independent cohorts of 658 patients. The CCNB1 signature was shown to be an independent risk factor by a multivariate analysis and subset stratification according to stage and grade [HR, 2.93; 95% confidence intervals (CI), 1.302–6.594; P = 0.009]. The subset analysis also revealed that the signature could identify patients who would benefit from IVT. Finally, gene network analyses and experimental assays indicated that NMIBC recurrence could be mediated by FOXM1–CCNB1–Fanconi anemia pathways.Conclusions: The CCNB1 signature represents a promising diagnostic tool to identify patients with NMIBC who have a high risk of recurrence and to predict response to IVT. Clin Cancer Res; 20(12); 3233–43. ©2014 AACR.
High On-Treatment Platelet Reactivity as a Risk Factor for Secondary Prevention After Coronary Stent Revascularization
Authors: Montalescot Gilles , Rangé Grégoire , Silvain Johanne , Bonnet Jean-Louis , Boueri Ziad , Barthélémy Olivier , Cayla Guillaume , Belle Loic , Van Belle Eric , Cuisset Thomas , Elhadad Simon , Pouillot Christophe , Henry Patrick , Motreff Pascal , Carrié Didier , Rousseau Hélène , Aubry Pierre , Monségu Jacques , Sabouret Pierre , O’Connor Stephen A. , Abtan Jérémie , Kerneis Mathieu , Saint-Etienne Christophe , Beygui Farzin , Vicaut Eric , Collet Jean-Philippe 
Published: April 2014

Background—
Individualizing antiplatelet therapy after platelet function testing did not improve outcome after coronary stenting in the Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting (ARCTIC) study. Whether results are different during the phase of secondary prevention starting after hospital discharge, when periprocedural events have been excluded, is unknown.

Methods and Results—

In ARCTIC, 2440 patients were randomized before coronary stenting to a strategy of platelet function monitoring (VerifyNow P2Y
12
/aspirin point-of-care assay) with drug adjustment in suboptimal responders to antiplatelet therapy or to a conventional strategy without monitoring and without drug or dose changes. We performed a landmark analysis starting at the time of hospital discharge evaluating the primary end point of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization through 1 year. After discharge, the primary end point occurred in 8.6% of patients in the monitoring arm and 7.9% in the conventional arm (hazard ratio, 1.105; 95% confidence interval, 0.835–1.461;
P
=0.48). Stent thrombosis or urgent revascularization occurred in 4.4% and 4.5% in the monitoring and conventional arms, respectively (
P
=0.99). There was no difference for any of the other ischemic end points. Major bleeding event rates were 1.8% in the monitoring arm and 2.8% in the conventional arm (
P
=0.11), whereas major or minor bleeding event rates were 2.3% and 3.4%, respectively (
P
=0.10).

Conclusions—
Detection of platelet hyper-reactivity by platelet function testing in patients undergoing coronary stenting with further therapeutic adjustment does not reduce ischemic recurrences after intervention. On-treatment platelet hyperreactivity cannot be considered as a risk factor requiring intervention for secondary prevention after percutaneous coronary revascularization.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00827411.