bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal smokeless tobacco use in Alaska Native women and singleton infant birth size
Authors: ENGLAND LUCINDA J. , KIM SHIN Y. , SHAPIRO‐MENDOZA CARRIE K. , WILSON HOYT G. , KENDRICK JULIETTE S. , SATTEN GLEN A. , LEWIS CLAIRE A. , WHITTERN PERSENIA , TUCKER MYRA J. , CALLAGHAN WILLIAM M. 
Published: September 2011

AbstractObjective. To examine the effects of maternal prenatal smokeless tobacco use on infant birth size. Design. A retrospective medical record review of 502 randomly selected deliveries. Population and Setting. Singleton deliveries to Alaska Native women residing in a defined geographical region in western Alaska, 1997–2005. Methods. A regional medical center's electronic records were used to identify singleton deliveries. Data on maternal tobacco exposure and pregnancy outcomes were abstracted from medical records. Logistic models were used to estimate adjusted mean birthweight, length and head circumference for deliveries to women who used no tobacco (n=121), used smokeless tobacco (n=237) or smoked cigarettes (n=59). Differences in mean birthweight, length and head circumference, 95% confidence intervals and p‐values were calculated using non‐users as the reference group. Main Outcome Measures. Infant birthweight, crown–heel length and head circumference. Results. After adjustment for gestational age and other potential confounders, the mean birthweight of infants of smokeless tobacco users was reduced by 78g compared with that of infants of non‐users (p=0.18) and by 331g in infants of smokers (p<0.01). No association was found between maternal smokeless tobacco use and infant length or infant head circumference. Conclusions. We found a modest but non‐significant reduction in the birthweight of infants of smokeless tobacco users compared with infants of tobacco non‐users. Because smokeless tobacco contains many toxic compounds that could affect other pregnancy outcomes, results of this study should not be construed to mean that smokeless tobacco use is safe during pregnancy.
Vascular Calcification in Patients With Chronic Kidney Disease
Authors: Nitta Kosaku 
Published: September 2011

AbstractVascular calcification is very prevalent in patients with chronic kidney disease (CKD). In addition to having more traditional cardiovascular (CV) risk factors, CKD patients also have a number of non‐traditional CV risk factors that may play a prominent role in the pathogenesis of vascular calcification. The transformation of vascular smooth muscle cells into osteoblast‐like cells seems to be a key element in the pathogenesis of vascular calcification in the presence of calcium (Ca) and phosphorus (P) deposition due to abnormal bone metabolism and impaired renal excretion. Vascular calcification causes increased arterial stiffness, left ventricular hypertrophy, decreased coronary artery perfusion, myocardial ischemia, and increased cardiovascular morbidity and mortality. Although current treatment strategies focus on correcting abnormal Ca, P, parathyroid hormone, or vitamin D levels in CKD, a better understanding of the mechanisms of abnormal tissue calcification may lead to the development of new therapeutic agents that are capable of reducing vascular calcification and improving the CV outcome of CKD patients. This review article summarizes the following: (i) the pathophysiological mechanism responsible for vascular calcification; (ii) the methods of detecting vascular calcification in CKD patients; and (iii) the treatment of vascular calcification in CKD patients.
Mindfulness‐ and acceptance‐based interventions for anxiety disorders: A systematic review and meta‐analysis
Authors: Vøllestad Jon , Nielsen Morten Birkeland , Nielsen Geir Høstmark 
Published: September 2011

Purpose. Mindfulness‐ and acceptance‐based interventions (MABIs) are receiving increasing attention in the treatment of mental disorders. These interventions might be beneficial for patients with anxiety disorders, but no prior reviews have comprehensively investigated the effects of this family of interventions on clinical samples. The aim of this study was to review and synthesize extant research on MABIs for patients with diagnoses of anxiety disorders.Methods. We conducted a systematic search of relevant databases according to pre‐defined criteria. Studies were eligible for inclusion if they employed MABIs for patients diagnosed with anxiety disorders.Results. Nineteen eligible studies were found. Meta‐analysis of within‐group pre‐ to post‐treatment effects yielded overall Hedges’g effect sizes of 1.08 for anxiety symptoms and 0.85 for depression symptoms. For controlled studies, overall between‐group Hedges’g was 0.83 for anxiety symptoms and 0.72 for depression symptoms. Moderator analyses examined whether intervention type, design, treatment dosage, or patient sample was associated with systematic variation in effect sizes. No significant moderating effects were found on the variables examined, apart from an observed superiority in effect size for clinical trials on samples of patients with mixed anxiety disorders. However, differential effect sizes indicated benefits of adding specific psychotherapeutic content to mindfulness training, as well as an advantage of individual over group treatment.Conclusions. MABIs are associated with robust and substantial reductions in symptoms of anxiety and comorbid depressive symptoms. More research is needed to determine the efficacy of MABIs relative to current treatments of choice, and to clarify the contribution of processes of mindfulness and acceptance to observed outcome.
Reduction in the exposure to being out-of-position among car occupants who used a sleeping device
Authors: Lopez-Valdes Francisco J , Fernandez-Bolanos Martin Marta , Alvarez Ruiz-Larrinaga Ainhoa , Segui-Gomez Maria 
Published: September 2011

BackgroundThis study assesses the impact on safety of a system designed to enhance sleep in car passengers. The system holds the head posteriorly and limits its rotation in the sagittal and frontal planes, modifying the occupant's head position. This device may have an influence on the interaction between the occupant and the vehicle restraint systems.MethodsIt was a randomised, prospective, single-blind, cross-over controlled study in which 41 volunteers were exposed to using the system while riding as car passengers. Whether the device influenced the posture of the occupants and prevented them from adopting out-of-position (OOP) configurations was also analysed. Occupants were videotaped while they were using both the innovative system (cases) and their normal sleeping device (controls), if any.ResultsControls were exposed to OOP situations in 825 occasions (18.4%; 95% CI 17.3% to 19.6%), while cases were exposed in 416 occasions (9.3%; 95% CI 8.4% to 10.2%). The paper also analysed how many cases and controls were exposed at least once to a particular event and how frequent a single participant incurred in an OOP situation. In both cases, the innovative device showed a reduction in exposition. When OOP situations were grouped into severe, moderate and minor events, the innovative device produced a statistically significant reduction in the occurrence of severe and moderate events.ConclusionsA device originally designed to improve comfort and rest in car passengers has been found to reduce the exposure of the occupants to being OOP while resting in the car.Trial registration numberhttp://www.ClinicalTrials.gov,NCT01062295.
Herpes simplex virus type 2 serological testing and psychosocial harm: a systematic review
Authors: Ross Kaile , Johnston Christine , Wald Anna 
Published: September 2011

BackgroundSerological testing for herpes simplex virus (HSV) type 2 in persons without a history of genital herpes is not recommended, partly because of concerns that an HSV-2 diagnosis would lead to negative psychosocial sequelae. This review aimed to examine the evidence regarding the psychosocial effects of HSV-2 serological testing.MethodsEight electronic databases were searched for empirical studies indexed before March 2010. Abstracts from relevant conferences were reviewed and senior authors contacted to find unpublished materials. Eligible studies examined participants without a history of genital herpes who underwent HSV-2 serological testing and reported data from at least one quantitative or qualitative psychosocial assessment conducted after receiving HSV results.ResultsOf nine studies that satisfied the inclusion criteria, seven reported that HSV-2 diagnosis by serological test did not have a persistent negative impact on 309 participants' mental health or sexual attitude and satisfaction. Two studies reported a negative impact of testing; one found that five HSV-2-seropositive college students had increased distress 3 months post-testing compared with HSV-2-negative individuals, and the other found self-reports of sexual undesirability up to 1 year after diagnosis in some people. The perceived severity of a genital herpes diagnosis was moderately severe for participants before testing; however, post-testing, the reported severity of a herpes diagnosis was lower among those testing HSV-2 positive.ConclusionsHSV-2 diagnosis by type-specific serological testing did not result in long-term psychosocial harm in most persons without an identified history of genital herpes. Concerns about sustained emotional impact should not deter clinicians from offering HSV-2 serological testing to appropriate patients.
Long-lived Inflammatory Signaling in Irradiated Bone Marrow Is Genome Dependent
Authors: Lorimore Sally A. , Mukherjee Debayan , Robinson Joanne I. , Chrystal Jennifer A. , Wright Eric G. 
Published: September 2011

Abstract
Ionizing radiation is carcinogenic, but genotype is a key determinant of susceptibility. Mutational DNA damage is generally attributed to cause disease, but irradiation also affects multicellular interactions as a result of poorly understood bystander effects that may influence carcinogenic susceptibility. In this study, we show that the bone marrow of irradiated mice will retain the ability to kill hemopoietic clonogenic stem cells and to induce chromosomal instability for up to 3 months after irradiation. Chromosomal instability was induced in bone marrow cells derived from CBA/Ca mice, a strain that is susceptible to radiation-induced acute myeloid leukemia (r-AML), but not in C57BL6 mice that are resistant to r-AML. Similarly, clonogenic cell lethality was exhibited in C57BL/6 mice but not CBA/Ca mice. Mechanistic investigations revealed that these genotype-dependent effects involved cytokine-mediated signaling and were mediated by a cyclooxygenase-2–dependent mechanism. Thus, our results suggested that inflammatory processes were responsible for mediating and sustaining the durable effects of ionizing radiation observed on bone marrow cells. Because most exposures to ionizing radiation are directed to only part of the body, our findings imply that genotype-directed tissue responses may be important determinants of understanding the specific consequence of radiation exposure in different individuals. Cancer Res; 71(20); 6485–91. ©2011 AACR.
Antitumor Activity of the Investigational Proteasome Inhibitor MLN9708 in Mouse Models of B-cell and Plasma Cell Malignancies
Authors: Lee Edmund C. , Fitzgerald Michael , Bannerman Bret , Donelan Jill , Bano Kristen , Terkelsen Jennifer , Bradley Daniel P. , Subakan Ozlem , Silva Matthew D. , Liu Ray , Pickard Michael , Li Zhi , Tayber Olga , Li Ping , Hales Paul , Carsillo Mary , Neppalli Vishala T. , Berger Allison J. , Kupperman Erik , Manfredi Mark , Bolen Joseph B. , Van Ness Brian , Janz Siegfried 
Published: September 2011

Abstract
Purpose: The clinical success of the first-in-class proteasome inhibitor bortezomib (VELCADE) has validated the proteasome as a therapeutic target for treating human cancers. MLN9708 is an investigational proteasome inhibitor that, compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and antitumor activity in preclinical studies. Here, we focused on evaluating the in vivo activity of MLN2238 (the biologically active form of MLN9708) in a variety of mouse models of hematologic malignancies, including tumor xenograft models derived from a human lymphoma cell line and primary human lymphoma tissue, and genetically engineered mouse (GEM) models of plasma cell malignancies (PCM).
Experimental Design: Both cell line–derived OCI-Ly10 and primary human lymphoma–derived PHTX22L xenograft models of diffuse large B-cell lymphoma were used to evaluate the pharmacodynamics and antitumor effects of MLN2238 and bortezomib. The iMycCα/Bcl-XL GEM model was used to assess their effects on de novo PCM and overall survival. The newly developed DP54-Luc–disseminated model of iMycCα/Bcl-XL was used to determine antitumor activity and effects on osteolytic bone disease.
Results: MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with bortezomib in both OCI-Ly10 and PHTX22L models. Although both MLN2238 and bortezomib prolonged overall survival, reduced splenomegaly, and attenuated IgG2a levels in the iMycCα/Bcl-XL GEM model, only MLN2238 alleviated osteolytic bone disease in the DP54-Luc model.
Conclusions: Our results clearly showed the antitumor activity of MLN2238 in a variety of mouse models of B-cell lymphoma and PCM, supporting its clinical development. MLN9708 is being evaluated in multiple phase I and I/II trials. Clin Cancer Res; 17(23); 7313–23. ©2011 AACR.
Inhibition of Focal Adhesion Kinase by PF-562,271 Inhibits the Growth and Metastasis of Pancreatic Cancer Concomitant with Altering the Tumor Microenvironment
Authors: Stokes Jayme B. , Adair Sara J. , Slack-Davis Jill K. , Walters Dustin M. , Tilghman Robert W. , Hershey E. Dan , Lowrey Bryce , Thomas Keena S. , Bouton Amy H. , Hwang Rosa F. , Stelow Edward B. , Parsons J. Thomas , Bauer Todd W. 
Published: September 2011

Abstract
Current therapies for pancreatic ductal adenocarcinoma (PDA) target individual tumor cells. Focal adhesion kinase (FAK) is activated in PDA, and levels are inversely associated with survival. We investigated the effects of PF-562,271 (a small-molecule inhibitor of FAK/PYK2) on (i) in vitro migration, invasion, and proliferation; (ii) tumor proliferation, invasion, and metastasis in a murine model; and (iii) stromal cell composition in the PDA microenvironment. Migration assays were conducted to assess tumor and stromal cell migration in response to cellular factors, collagen, and the effects of PF-562,271. An orthotopic murine model was used to assess the effects of PF-562,271 on tumor growth, invasion, and metastasis. Proliferation assays measured PF-562,271 effects on in vitro growth. Immunohistochemistry was used to examine the effects of FAK inhibition on the cellular composition of the tumor microenvironment. FAK and PYK2 were activated and expressed in patient-derived PDA tumors, stromal components, and human PDA cell lines. PF-562,271 blocked phosphorylation of FAK (phospho-FAK or Y397) in a dose-dependent manner. PF-562,271 inhibited migration of tumor cells, cancer-associated fibroblasts, and macrophages. Treatment of mice with PF-562,271 resulted in reduced tumor growth, invasion, and metastases. PF-562,271 had no effect on tumor necrosis, angiogenesis, or apoptosis, but it did decrease tumor cell proliferation and resulted in fewer tumor-associated macrophages and fibroblasts than control or gemcitabine. These data support a role for FAK in PDA and suggest that inhibitors of FAK may contribute to efficacious treatment of patients with PDA. Mol Cancer Ther; 10(11); 2135–45. ©2011 AACR.
Tasisulam Sodium, an Antitumor Agent That Inhibits Mitotic Progression and Induces Vascular Normalization
Authors: Meier Timothy , Uhlik Mark , Chintharlapalli Sudhakar , Dowless Michele , Van Horn Robert , Stewart Julie , Blosser Wayne , Cook James , Young Debra , Ye Xiang , Evans Glenn , Credille Kelly , Ballard Darryl , Huber Lysiane , Capen Andrew , Chedid Marcio , Ilaria Robert , Smith Michele C. , Stancato Louis 
Published: September 2011

AbstractLY573636-sodium (tasisulam) is a small molecule antitumor agent with a novel mechanism of action currently being investigated in a variety of human cancers. In vitro, tasisulam induced apoptosis via the intrinsic pathway, resulting in cytochrome c release and caspase-dependent cell death. Using high content cellular imaging and subpopulation analysis of a wide range of in vitro and in vivo cancer models, tasisulam increased the proportion of cells with 4N DNA content and phospho-histone H3 expression, leading to G2–M accumulation and subsequent apoptosis. Tasisulam also blocked VEGF, epidermal growth factor, and fibroblast growth factor–induced endothelial cell cord formation but did not block acute growth factor receptor signaling (unlike sunitinib, which blocks VEGF-driven angiogenesis at the receptor kinase level) or induce apoptosis in primary endothelial cells. Importantly, in vivo phenocopying of in vitro effects were observed in multiple human tumor xenografts. Tasisulam was as effective as sunitinib at inhibiting neovascularization in a Matrigel plug angiogenesis assay in vivo and also caused reversible, non G2–M–dependent growth arrest in primary endothelial cells. Tasisulam also induced vascular normalization in vivo. Interestingly, the combination of tasisulam and sunitinib significantly delayed growth of the Caki-1 renal cell carcinoma model, whereas neither agent was active alone. These data show that tasisulam has a unique, dual-faceted mechanism of action involving mitotic catastrophe and antiangiogenesis, a phenotype distinct from conventional chemotherapies and published anticancer agents. Mol Cancer Ther; 10(11); 2168–78. ©2011 AACR.
Micelle-Encapsulated Thiostrepton as an Effective Nanomedicine for Inhibiting Tumor Growth and for Suppressing FOXM1 in Human Xenografts
Authors: Wang Ming , Gartel Andrei L. 
Published: September 2011

Abstract
The thiazole antiobiotic, thiostrepton, has been found to induce cell death in cancer cells through proteasome inhibition. As a proteasome inhibitor, thiostrepton has also been shown to suppress the expression of FOXM1, the oncogenic forkhead transcription factor overexpressed in cancer cells. In this study, we explored the potential in vivo anticancer properties of thiostrepton, delivered through nanoparticle encapsulation to xenograft models of breast and liver cancer. We encapsulated thiostrepton into micelles assembled from amphiphilic lipid-PEG (polyethylene glycol) molecules, where thiostrepton is solubilized within the inner lipid compartment of the micelle. Upon assembly, hydrophobic thiostrepton molecules are solubilized into the lipid component of the micelle shell, formed through the self-assembly of amphipilic lipid-PEG molecules. Maximum accumulation of micelle-thiostrepton nanoparticles (100 nm in diameter, −16 mV in zeta potential) into tumors was found at 4 hours postadministration and was retained for at least 24 hours. Upon continuous treatment, we found that nanoparticle-encapsulated thiostrepton reduced tumor growth rates of MDA-MB-231 and HepG2 cancer xenografts. Furthermore, we show for the first time the in vivo suppression of the oncogenic FOXM1 after treatment with proteasome inhibitors. Immunoblotting and immunohistochemical staining also showed increased apoptosis in the treated tumors, as indicated by cleaved caspase-3 expression. Our data suggest that the thiazole antibiotic/proteasome inhibitor thiostrepton, when formulated into nanoparticles, may be highly suited as a nanomedicine for treating human cancer. Mol Cancer Ther; 10(12); 2287–97. ©2011 AACR.
Protein Phosphatase 2A Promotes Endothelial Survival via Stabilization of Translational Inhibitor 4E-BP1 Following Exposure to Tumor Necrosis Factor-α
Authors: Janzen Carla , Sen Suvajit , Cuevas Janis , Reddy Srinivasa T. , Chaudhuri Gautam 
Published: September 2011

Objective—
Tumor necrosis factor-α (TNFα) may change from a stimulator of reversible activation of endothelial cells (ECs) to a killer when combined with cycloheximide (CHX). The means by which endothelial cells are destined to either the survival pathway or the apoptotic pathway are not fully understood. We investigated the role of p38 mitogen-activated protein kinase (MAPK) and protein phosphatase 2A (PP2A) activation and their regulation of 4E-BP1 stability in ECs to determine whether this pathway contributes to apoptosis induced by TNFα and CHX.

Methods and Results—
Apoptosis was induced in human umbilical vein ECs (HUVECs) by treating them with a combination of TNFα and CHX (TNFα/CHX). Activation of p38 MAPK was increased in HUVECs undergoing apoptosis, which was associated with degradation of eukaryotic initiation factor 4A regulator 4E-BP1 in a p38 MAPK–dependent manner. CHX attenuated a TNFα-stimulated increase in the expression and activity of PP2A. Silencing PP2A expression with small interfering RNA transfection mimicked CHX sensitization, increasing HUVEC apoptosis with TNFα stimulation and suggesting a protective role for PP2A in the apoptotic process.

Conclusion—
Our data suggest that (1) TNFα stimulates PP2A and HUVECs elude apoptosis by PP2A-dependent dephosphorylation of p38 MAPK, and (2) CHX-induced inhibition of PP2A leads to maintenance of p38 activity and degradation of 4E-BP1, resulting in enhanced TNFα-induced apoptosis.
Genome-Wide Microarray Analyses Identify the Protein C Receptor as a Novel Calcineurin/Nuclear Factor of Activated T Cells–Dependent Gene in Vascular Smooth Muscle Cell Phenotypic Modulation
Authors: Lee Monica Y. , Garvey Sean M. , Ripley Marcia L. , Wamhoff Brian R. 
Published: September 2011

Objective—
Calcineurin (Cn) and the nuclear factor of activated T cells (NFAT) family of transcription factors are critical in vascular smooth muscle cell (SMC) development and pathology. Here, we used a genomics approach to identify and validate NFAT gene targets activated during platelet-derived growth factor-BB (PDGF-BB)–induced SMC phenotypic modulation.

Methods and Results—
Genome-wide expression arrays were used to identify genes both (1) differentially activated in response to PDGF-BB and (2) whose differential expression was reduced by both the Cn inhibitor cyclosporin A and the NFAT inhibitor A-285222. The 20 most pharmacologically sensitive genes were validated by quantitative reverse transcription–polymerase chain reaction analysis of PDGF-BB-stimulated SMCs in the presence of Cn/NFAT inhibitors, including the VIVIT peptide. In all experiments, protein C receptor (PROCR) gene activation was reduced. We showed that PROCR expression was virtually absent in untreated, quiescent SMCs. PDGF-BB stimulation, however, induced significant PROCR promoter activation and downstream protein expression in a Cn/NFAT-dependent manner. Mutation of a species-conserved, NFAT binding motif significantly attenuated PDGF-BB-induced PROCR promoter activity, thereby distinguishing NFAT as the first PROCR transcriptional activator to date. Moreover, SMC PROCR expression was upregulated in the neointima as early as 7 days following acute vascular injury in rat carotid arteries.

Conclusion—
We hereby report PROCR as a novel, NFAT-dependent gene that may be implicated in vascular restenosis and consequent inward remodeling.