bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of spontaneous miscarriage in euthyroid women with thyroid autoimmunity undergoing IVF: a meta-analysis
Authors: Toulis Konstantinos A , Goulis Dimitrios G , Venetis Christos A , Kolibianakis Efstratios M , Negro Roberto , Tarlatzis Basil C , Papadimas Ioannis 
Published: December 2009

ObjectiveTo investigate whether thyroid autoimmunity (TAI) is associated with increased risk for spontaneous miscarriage in subfertile, euthyroid women undergoing IVF.DesignMeta-analysis of observational studies.Patient(s)Four prospective studies that reported data on 1098 subfertile women undergoing IVF (141 with TAI and 957 controls) were included in the meta-analysis.Main outcome measureMiscarriage risk ratio (RR).Secondary outcome measuresClinical pregnancy rate and delivery rate.Result(s)Euthyroid, subfertile women with TAI undergoing IVF demonstrated significantly higher risk for miscarriage compared with controls (four studies–fixed effects RR: 1.99, 95% confidence interval: 1.42– 2.79, P<0.001). No significant difference in clinical pregnancy and delivery rates was detected between groups.ConclusionBased on the currently available evidence, it appears that the presence of TAI is associated with an increased risk for spontaneous miscarriage in subfertile women achieving a pregnancy through an IVF procedure.
Transient Cooling of Ultrathin Epitaxial Bi(111)-Films on Si(111) Upon Femtosecond Laser Excitation Studied by Ultrafast Reflection High Energy Electron Diffraction
Authors: Hanisch-Blicharski Anja , Krenzer Boris , Möllenbeck Simone , Ligges Manuel , Zhou Ping , Kammler Martin , Horn-von Hoegen Michael 
Published: December 2009

AbstractWith time resolved ultrafast electron diffraction the cooling process across the interface between a thin film and the underlying substrate was studied after excitation with short laser pulses. From the exponential decay of the surface temperature evolution a thermal boundary conductance of 1430 W/(cm2K) is determined for a 9.7 nm thin Bi(111) film on Si(111). A linear dependence between laser fluence and initial temperature rise was measured for film-thicknesses between 2.5 nm and 34.5 nm. The ratio of initial temperature rise and laser fluence for different film-thicknesses is compared to a model taking multilayer optics into account. The data agree well with this model.
Development of Multiple Myeloma in a Patient with Chronic Myeloid Leukemia While on Treatment with Imatinib Mesylate for 65 Months
Authors: Michael Michalis , Antoniades Marios , Lemesiou Elena , Papaminas Nicandros , Melanthiou Freiderikh 
Published: December 2009

Abstract
The simultaneous occurrence of multiple myeloma (MM) and chronic myeloid leukemia (CML) is an extremely rare event that has been reported in only eight cases in the literature. We report here on only the third case of the development of MM in a patient with CML on treatment with imatinib mesylate, and to our knowledge, this is the first case in a patient who received imatinib as first-line treatment.
Combined environmental risk assessment for 5-fluorouracil and capecitabine in Europe
Authors: Straub Jürg Oliver 
Published: December 2009

Abstract
An environmental risk assessment (ERA) was made for the old cytostatic active pharmaceutical ingredient 5-fluorouracil (5-FU) and for capecitabine (CAP), which is a prodrug of 5-FU. This ERA is based on published and company internal data as well as new test results for physicochemical, human metabolism, biodegradability, environmental partitioning and fate, and acute and chronic ecotoxicity properties of the active substance 5-FU as well as on use sales data for 5-FU and CAP in Europe. Predicted environmental concentrations (PECs) were extrapolated following the EMEA 2006 Guideline on ERA for human pharmaceuticals and the European Union 2003 Technical Guidance Document (TGD) for risk assessment as well as the TGD-based application EUSES v2.0. Actual amounts sold were taken from IMS Health Databases, in order to refine the default use and EMEA penetration factor as well as the PECs. Moreover, available measured environmental concentrations (MECs) were used to supplement PECs. A predicted no-effect concentration (PNEC) for 5-FU was derived from chronic ecotoxicity data. Except for the simplistic EMEA Phase I default PEC, the risk characterization by PEC:PNEC and MEC:PNEC ratios for various environmental compartments resulted in no significant risk. As the EMEA Phase I PEC does not integrate documented human metabolism and environmental degradation, in contrast to refined PEC derivations, it is inferred that the current use of CAP and 5-FU does not present any evident risk to the environment. An additional evaluation of persistence, bioaccumulation, and toxicity (PBT) properties supports the conclusion of no significant environmental risk for 5-FU and CAP. Integr Environ Assess Manag 2010;6:540–566. © 2009 SETAC
A new process for organizing assessments of social, economic, and environmental outcomes: Case study of wildland fire management in the USA
Authors: Bruins Randall JF , Munns Wayne R , Botti Stephen J , Brink Steve , Cleland David , Kapustka Larry , Lee Danny , Luzadis Valerie , Falk McCarthy Laura , Rana Naureen , Rideout Douglas B , Rollins Matt , Woodbury Peter , Zupko Mike 
Published: December 2009

Abstract
Ecological risk assessments typically are organized using the processes of planning (a discussion among managers, stakeholders, and analysts to clarify ecosystem management goals and assessment scope) and problem formulation (evaluation of existing information to generate hypotheses about adverse ecological effects, select assessment endpoints, and develop an analysis plan). These processes require modification to be applicable for integrated assessments that evaluate ecosystem management alternatives in terms of their ecological, economic, and social consequences. We present 8 questions that define the steps of a new process we term integrated problem formulation (IPF), and we illustrate the use of IPF through a retrospective case study comparing 2 recent phases of development of the Fire Program Analysis (FPA) system, a planning and budgeting system for the management of wildland fire throughout publicly managed lands in the United States. IPF extends traditional planning and problem formulation by including the explicit comparison of management alternatives, the valuation of ecological, economic and social endpoints, and the combination or integration of those endpoints. The phase 1, limited-prototype FPA system used a set of assessment endpoints of common form (i.e., probabilities of given flame heights over acres of selected land-resource types), which were specified and assigned relative weights at the local level in relation to a uniform national standard. This approach was chosen to permit system-wide optimization of fire management budget allocations according to a cost-effectiveness criterion. Before full development, however, the agencies abandoned this approach in favor of a phase 2 system that examined locally specified (rather than system-optimized) allocation alternatives and was more permissive as to endpoint form. We demonstrate how the IPF process illuminates the nature, rationale, and consequences of these differences, and argue that its early use for the FPA system may have enabled a smoother development path. Integr Environ Assess Manag 2010;6:469–483. © 2009 SETAC
CD14+ Monocytes Are Vulnerable and Functionally Impaired Under Endoplasmic Reticulum Stress in Patients With Type 2 Diabetes
Authors: Komura Takuya , Sakai Yoshio , Honda Masao , Takamura Toshinari , Matsushima Kouji , Kaneko Shuichi 
Published: December 2009

OBJECTIVE
Although patients with diabetes suffer from increased infections and a higher incidence of cancer due to impaired immune function, details on diabetes-induced decrease in immunity are lacking. We assessed how immune-mediating peripheral blood mononuclear cells (PBMCs) are affected in diabetes.

RESEARCH DESIGN AND METHODS
From 33 patients with type 2 diabetes and 28 healthy volunteers, we obtained PBMCs and investigated their susceptibility to apoptosis and functional alteration.

RESULTS
In a subpopulation of PBMCs, monocytes derived from patients with diabetes were more susceptible to apoptosis than monocytes from healthy volunteers. Monocytes from patients with diabetes had decreased phagocytotic activity and were less responsive to Toll-like receptor (TLR) ligands, although the expression of TLRs did not differ significantly between the two groups. Furthermore, monocytes from patients with diabetes had a distinctly different gene expression profile compared with monocytes from normal volunteers as assessed with DNA microarray analysis. Specifically, quantitative real-time detection PCR measurements showed an elevated expression of the markers of endoplasmic reticulum (ER) stress in diabetic monocytes, and electron microscopic examination of monocytes revealed morphologic alterations in the ER of cells derived from patients with diabetes. Consistently, the ER stress inducer tunicamycin increased apoptosis of otherwise healthy monocytes and attenuated the proinflammatory responses to TLR ligands.

CONCLUSIONS
These data suggest that monocytes comprise a substantially impaired subpopulation of PBMCs in patients with diabetes and that ER stress is involved in these pathologic changes mechanistically. This implies that the affected monocytes should be investigated further to better understand diabetic immunity.
Association Between Raised Inflammatory Markers and Cognitive Decline in Elderly People With Type 2 Diabetes
Authors: Marioni Riccardo E. , Strachan Mark W.J. , Reynolds Rebecca M. , Lowe Gordon D.O. , Mitchell Rory J. , Fowkes F. Gerry R. , Frier Brian M. , Lee Amanda J. , Butcher Isabella , Rumley Ann , Murray Gordon D. , Deary Ian J. , Price Jackie F. 
Published: December 2009

OBJECTIVETo determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes.RESEARCH DESIGN AND METHODSA cross-sectional study of 1,066 men and women aged 60–75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary–based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood sample at the time of cognitive testing.RESULTSHigher IL-6 and TNF-α levels were associated with poorer age- and sex-adjusted scores on the majority of the individual cognitive tests. They were also associated with g using standardized regression coefficients −0.074 to −0.173 (P &lt; 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, IL-6 remained associated with three of the cognitive tests and with g.CONCLUSIONSIn this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline.
Leptin and Soluble Leptin Receptor Levels in Plasma and Risk of Type 2 Diabetes in U.S. Women
Authors: Sun Qi , van Dam Rob M. , Meigs James B. , Franco Oscar H. , Mantzoros Christos S. , Hu Frank B. 
Published: December 2009

OBJECTIVE
We prospectively examined plasma levels of leptin and soluble leptin receptor (sOB-R), as well as their interactions with other diabetes risk factors, in relation to type 2 diabetes to elucidate the complex relation between these two biomarkers and diabetes risk.

RESEARCH DESIGN AND METHODS
Of 32,826 Nurses' Health Study participants who provided blood samples during 1989–1990, 1,054 incident case subjects of type 2 diabetes were identified and confirmed during 1990–2004 and 1,254 matched control subjects were selected. Plasma leptin and sOB-R levels were measured among these participants.

RESULTS
After multivariate adjustment for BMI, lifestyle practices, and dietary factors, sOB-R levels were significantly associated with a lower risk of type 2 diabetes. In comparison with women in the lowest quintile, the ORs (95% CI) of developing type 2 diabetes were 0.73 (0.55–0.96), 0.51 (0.38–0.68), 0.42 (0.31–0.57), and 0.39 (0.28–0.54; P for trend &lt; 0.0001) for women in the second to fifth quintiles of sOB-R levels, respectively. In contrast, plasma leptin levels were not significantly associated with the risk of type 2 diabetes: The OR (95% CI) was 0.82 (0.62–1.10; P for trend = 0.46) comparing the highest with the lowest quintile of leptin levels. sOB-R levels were consistently associated with a decreased risk of type 2 diabetes at various levels of leptin or high-molecular-weight adiponectin.

CONCLUSIONS
These data suggest a strong inverse association between plasma sOB-R levels and risk of type 2 diabetes, independent of BMI, leptin, and adiponectin levels.
Some Factors Predict Successful Short-Term Outcomes in Individuals With Shoulder Pain Receiving Cervicothoracic Manipulation: A Single-Arm Trial
Authors: Mintken Paul E. , Cleland Joshua A. , Carpenter Kristin J. , Bieniek Melanie L. , Keirns Mike , Whitman Julie M. 
Published: December 2009

BackgroundIt has been reported that manipulative therapy directed at the cervical and thoracic spine may improve outcomes in patients with shoulder pain. To date, limited data are available to help physical therapists determine which patients with shoulder pain may experience changes in pain and disability following the application of these interventions.ObjectiveThe purpose of this study was to identify prognostic factors from the history and physical examination in individuals with shoulder pain who are likely to experience rapid improvement in pain and disability following cervical and thoracic spine manipulation.DesignThis was a prospective single-arm trial.SettingThis study was conducted in outpatient physical therapy clinics.ParticipantsThe participants were individuals who were seen by physical therapists for a primary complaint of shoulder pain.Intervention and MeasurementsParticipants underwent a standardized examination and then a series of thrust and nonthrust manipulations directed toward the cervicothoracic spine. Individuals were classified as having achieved a successful outcome at the second and third sessions based on their perceived recovery. Potential prognostic variables were entered into a stepwise logistic regression model to determine the most accurate set of variables for prediction of treatment success.ResultsData for 80 individuals were included in the data analysis, of which 49 had a successful outcome. Five prognostic variables were retained in the final regression model. If 3 of the 5 variables were present, the chance of achieving a successful outcome improved from 61% to 89% (positive likelihood ratio=5.3).LimitationsA prospective single-arm trial lacking a control group does not allow for inferences to be made regarding cause and effect. The statistical procedures used may result in “overfitting” of the model, which can result in low precision of the prediction accuracy, and the bivariate analysis may have resulted in the rejection of some important variables.ConclusionsThe identified prognostic variables will allow clinicians to make an a priori identification of individuals with shoulder pain who are likely to experience short-term improvement with cervical and thoracic spine manipulation. Future studies are necessary to validate these findings.
Ablation of Tumor Progression Locus 2 Promotes a Type 2 Th Cell Response in Ovalbumin-Immunized Mice
Authors: Watford Wendy T. , Wang Chun-Chi , Tsatsanis Christos , Mielke Lisa A. , Eliopoulos Aristides G. , Daskalakis Constantine , Charles Nicolas , Odom Sandra , Rivera Juan , O’Shea John , Tsichlis Philip N. 
Published: December 2009

Abstract
The protein kinase encoded by the Tpl2 proto-oncogene regulates ERK activation and cytokine gene expression in macrophages in response to LPS and TNF-α. In this study we show that OVA-immunized Tpl2−/− mice express high levels of IgE and develop more severe bronchoalveolar eosinophilic inflammation than Tpl2+/+ controls, when challenged with OVA intranasally. Bronchoalveolar exudates and supernatants of OVA-stimulated splenocytes from immunized Tpl2−/− mice express elevated levels of IL-4 and IL-5, suggesting that Tpl2 ablation promotes the Th2 polarization of the T cell response. Anti-CD3 stimulation of CD4+ T cells of wild-type and Tpl2 knockout mice revealed that Tpl2 ablation gives rise to a cell autonomous T cell defect that is primarily responsible for the Th2 polarization of the T cell response to Ag. This observation was further supported by experiments addressing the expression of Th1 and Th2 cytokines in OVA-stimulated mixed cultures of CD4+ T cells from Tpl2+/+/OT2 or Tpl2−/−/OT2 mice and dendritic cells from Tpl2+/+ or Tpl2−/− mice. Further studies revealed that Th1 cells express significantly higher levels of Tpl2 than Th2 cells. As a result, Tpl2−/− Th1 cells exhibit a stronger defect in ERK activation by anti-CD3 than Th2 cells and express low levels of T-bet. Given that the development of Th1 and Th2 cells depends on positive feedback signals from the T cells, themselves, the functional defect of the Tpl2−/− Th1 cells provides a mechanistic explanation for the T cell autonomous Th2 polarization in Tpl2−/− mice.
A High-Affinity Inhibitor of Human CD59 Enhances Complement-Mediated Virolysis of HIV-1: Implications for Treatment of HIV-1/AIDS
Authors: Hu Weiguo , Yu Qigui , Hu Ningjie , Byrd Daniel , Amet Tohti , Shikuma Cecilia , Shiramizu Bruce , Halperin Jose A. , Qin Xuebin 
Published: December 2009

Abstract
Many pathogenic enveloped viruses, including HIV-1, escape complement-mediated virolysis by incorporating host cell regulators of complement activation into their own viral envelope. The presence of complement regulators including CD59 on the external surface of the viral envelope confers resistance to complement-mediated virolysis, which may explain why human pathogenic viruses such as HIV-1 are not neutralized by complement in human fluids, even in the presence of high Ab titers against the viral surface proteins. In this study, we report the development of a recombinant form of the fourth domain of the bacterial toxin intermedilysin (the recombinant domain 4 of intermedilysin [rILYd4]), a 114 aa protein that inhibits human CD59 function with high affinity and specificity. In the presence of rILYd4, HIV-1 virions derived from either cell lines or peripheral blood mononuclear cells of HIV-1–infected patients became highly sensitive to complement-mediated lysis activated by either anti–HIV-1 gp120 Abs or by viral infection-induced Abs present in the plasma of HIV-1–infected individuals. We also demonstrated that rILYd4 together with serum or plasma from HIV-1–infected patients as a source of anti–HIV-1 Abs and complement did not mediate complement-mediated lysis of either erythrocytes or peripheral blood mononuclear cells. These results indicate that rILYd4 may represent a novel therapeutic agent against HIV-1/AIDS
Overview of Mouse Models of Inflammatory Bowel Disease and Their Use in Drug Discovery
Authors: Maxwell Joseph R. , Viney Joanne L. 
Published: December 2009

AbstractInflammatory bowel disease (IBD), a condition that affects millions of individuals, encompasses two distinct conditions: Crohn's disease (CD) and ulcerative colitis (UC). CD is an inflammatory condition affecting any part of the digestive tract between the mouth and anus, but, most commonly, the ileum and colon. It is distinguished by the presence of granulomas in the mucosal tissue and patchy areas of transmural inflammation. UC is restricted to the colon and is manifest as continuous inflammation starting from the rectum and extending back towards the cecum. Inflammation in UC is primarily restricted to mucosal layers. Research is ongoing to understand the causality of these two diseases, and advances in understanding of their pathology have resulted from the variety of mouse models of IBD that have emerged since the early 1990s. Described in this unit are contemporary mouse models of these conditions and examples of their use in drug discovery.Curr. Protoc. Pharmacol. 47:5.57.1‐5.57.19. © 2009 by John Wiley & Sons, Inc.
Methods of Inducing Inflammatory Bowel Disease in Mice
Authors: Maxwell Joseph R. , Brown William A. , Smith Carole L. , Byrne Fergus R. , Viney Joanne L. 
Published: December 2009

AbstractAnimal models of experimentally induced inflammatory bowel disease (IBD) are useful for understanding more about the mechanistic basis of disease, identifying new targets for therapeutic intervention, and testing novel therapeutic agents. This unit provides detailed protocols for four of the most commonly used mouse models of experimentally induced intestinal inflammation: chemical induction of colitis by dextran sodium sulfate (DSS), hapten‐induced colitis via 2,4,6‐trinitrobenzene sulfonic acid (TNBS), Helicobacter–induced colitis in mdr1a−/− mice, and the CD4+ CD45RBhi SCID transfer colitis model. Curr. Protoc. Pharmacol. 47:5.58.1‐5.58.37. © 2009 by John Wiley & Sons, Inc.
Macromolecular Synthesis and Membrane Perturbation Assays for Mechanisms of Action Studies of Antimicrobial Agents
Authors: Cotsonas King Amy , Wu Liping 
Published: December 2009

AbstractThe definition and confirmation of the mechanism of action of an NCE is central to antimicrobial drug discovery. Most antibiotics currently in clinical use selectively target and block one or more bacterial macromolecular synthesis processes, e.g., DNA replication, RNA synthesis (transcription), protein synthesis (translation), cell wall (peptidoglycan) synthesis, and fatty acid (lipid) biosynthesis. This unit includes two protocols for determining the effect of test compounds on macromolecular synthesis, one in test tube format and the other in 96‐well plate format. A membrane potential depolarization protocol is also provided. Disruption of cell membrane integrity may be a legitimate mechanism of action for antibacterials, but it also may be the result of nonspecific cell membrane activity, an effect that must be ruled out for mammalian cells. These assays provide useful means for verifying inhibition of an intended target pathway with investigational antimicrobial compounds. They can also be used as valuable secondary assays for lead optimization to eliminate inhibitors that display nonselective toxicity. Curr. Protoc. Pharmacol. 47:13A.7.1‐13A.7.23. © 2009 by John Wiley & Sons, Inc.
The UCSC Genome Browser
Authors: Karolchik Donna , Hinrichs Angie S. , Kent W. James 
Published: December 2009

AbstractThe University of California Santa Cruz (UCSC) Genome Browser is a popular Web‐based tool for quickly displaying a requested portion of a genome at any scale, accompanied by a series of aligned annotation “tracks.” The annotations—generated by the UCSC Genome Bioinformatics Group and external collaborators—display gene predictions, mRNA and expressed sequence tag alignments, simple nucleotide polymorphisms, expression and regulatory data, phenotype and variation data, and pairwise and multiple‐species comparative genomics data. All information relevant to a region is presented in one window, facilitating biological analysis and interpretation. The database tables underlying the Genome Browser tracks can be viewed, downloaded, and manipulated using another Web‐based application, the UCSC Table Browser. Users can upload data as custom annotation tracks in both browsers for research or educational use. This unit describes how to use the Genome Browser and Table Browser for genome analysis, download the underlying database tables, and create and display custom annotation tracks. Curr. Protoc. Bioinform. 28:1.4.1‐1.4.26. © 2009 by John Wiley & Sons, Inc.