bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in Targeting Human Epidermal Growth Factor Receptor-2 Signaling for Cancer Therapy
Authors: Meric-Bernstam Funda , Hung Mien-Chie 
Published: November 2006

Abstract
Human epidermal growth factor receptor (HER)-2 is a member of the HER tyrosine kinase family, which regulates cell growth and proliferation. HER-2 is overexpressed in 20% to 30% of breast cancers and has been associated with an aggressive phenotype and a poorer prognosis, making it an appealing therapeutic target. Since 1998, the anti-HER-2 antibody trastuzumab has been used for the treatment of women with HER-2-positive metastatic breast cancer. Results from large trials have established a role for trastuzumab in the adjuvant setting for the treatment of high-risk primary breast cancer as well. Tyrosine kinase inhibitors that target HER-2 are also very promising therapies and are likely to be incorporated into clinical practice in the near future. HER-2-targeted therapies represent a major step forward in achieving our goal of delivering individualized targeted therapy for breast cancer. However, there are many unanswered questions about the optimal use of these agents. Ongoing research will better elucidate the best combination therapies to overcome resistance to HER-2-targeted agents and will help identify patients at high enough risk to warrant their toxicity.
A Central Role for Nicotinic Cholinergic Regulation of Growth Factor–Induced Endothelial Cell Migration
Authors: Ng Martin K.C. , Wu Jenny , Chang Edwin , Wang Bing-yin , Katzenberg-Clark Regina , Ishii-Watabe Akiko , Cooke John P. 
Published: November 2006

Objective—An endothelial nicotinic acetylcholine receptor (nAChR) participates in atherogenesis and tumorigenesis by promoting neovascularization. To date, the mechanisms of nAChR-mediated angiogenesis and their relationship to angiogenic factors, eg, VEGF and bFGF, are unknown.Methods and Results—Nicotine induced dose-dependent human microvascular endothelial cell (HMVEC) migration, a key angiogenesis event, to an extent which was equivalent in magnitude to bFGF (10 ng/mL) but less than for VEGF (10 ng/mL). Unexpectedly, nAChR antagonism not only abolished nicotine-induced HMVEC migration but also abolished migration induced by bFGF and attenuated migration induced by VEGF. Transcriptional profiling identified gene expression programs which were concordantly regulated by all 3 angiogens (nicotine, VEGF, and bFGF), a notable feature of which includes corepression of thioredoxin-interacting protein (TXNIP), endogenous inhibitor of the redox regulator thioredoxin. Furthermore, TXNIP repression by all 3 angiogens induced thioredoxin activity. Silencing thioredoxin by small interference RNA abrogated all angiogen-induced migration while silencing TXNIP strongly induced HMVEC migration. Interestingly, nAChR antagonism abrogates growth factor (VEGF and bFGF)–mediated induction of thioredoxin activity.Conclusions—Nicotine promotes angiogenesis via stimulation of nAChR-dependent endothelial cell migration. Furthermore, growth factor–induced HMVEC migration, a key angiogenesis event, requires nAChR activation—an effect mediated in part by nAChR-dependent regulation of thioredoxin activity.
Disciples of the Deep Desert: Windesheim Biographers and the Imitation of the Desert Fathers
Authors: van Dijk Mathilde 
Published: November 2006

AbstractThis article examines how biographers from the Chapter of Windesheim construed their brothers and sisters as the new desert fathers. In the Devotio Moderna, these first hermits, monks, and nuns were regarded as the epitomes of what true piety was about. Windesheim biographers like John Busch put their subjects forward as the new practitioners of true piety, as it had been coined by the desert fathers. But what did this mean to them? How did they interpret the desert father material? How did they use it to create new examples for religious practice?
The Hydrologic Feedback Pathway for Land–Climate Coupling
Authors: Dirmeyer Paul A. 
Published: November 2006

Abstract
The impact of improvements in land surface initialization and specification of observed rainfall in global climate model simulations of boreal summer are examined to determine how the changes propagate around the hydrologic cycle in the coupled land–atmosphere system. On the global scale, about 70% of any imparted signal in the hydrologic cycle is lost in the transition from atmosphere to land, and 70% of the remaining signal is lost from land to atmosphere. This means that globally, less than 10% of the signal of any change survives the complete circuit of the hydrologic cycle in this model. Regionally, there is a great deal of variability. Specification of observed precipitation to the land component of the climate model strongly communicates its signal to soil wetness in rainy regions, but predictive skill in evapotranspiration arises primarily in dry regions. A maximum in signal transmission to model precipitation exists in between, peaking where mean rainfall rates are 1.5–2 mm day−1. It appears that the nature of the climate system inherently limits to these regions the potential impact on prediction of improvements in the ability of models to simulate the water cycle. Land initial conditions impart a weaker signal on the system than replacement of precipitation, so a weaker response is realized in the system, focused mainly in dry regions.
Simulation of Global Land Surface Conditions from 1948 to 2004. Part I: Forcing Data and Evaluations
Authors: Qian Taotao , Dai Aiguo , Trenberth Kevin E. , Oleson Keith W. 
Published: November 2006

Abstract
Because of a lack of observations, historical simulations of land surface conditions using land surface models are needed for studying variability and changes in the continental water cycle and for providing initial conditions for seasonal climate predictions. Atmospheric forcing datasets are also needed for land surface model development. The quality of atmospheric forcing data greatly affects the ability of land surface models to realistically simulate land surface conditions. Here a carefully constructed global forcing dataset for 1948–2004 with 3-hourly and T62 (∼1.875°) resolution is described, and historical simulations using the latest version of the Community Land Model version 3.0 (CLM3) are evaluated using available observations of streamflow, continental freshwater discharge, surface runoff, and soil moisture. The forcing dataset was derived by combining observation-based analyses of monthly precipitation and surface air temperature with intramonthly variations from the National Centers for Environmental Prediction–National Center for Atmospheric Research (NCEP–NCAR) reanalysis, which is shown to have spurious trends and biases in surface temperature and precipitation. Surface downward solar radiation from the reanalysis was first adjusted for variations and trends using monthly station records of cloud cover anomaly and then for mean biases using satellite observations during recent decades. Surface specific humidity from the reanalysis was adjusted using the adjusted surface air temperature and reanalysis relative humidity. Surface wind speed and air pressure were interpolated directly from the 6-hourly reanalysis data. Sensitivity experiments show that the precipitation adjustment (to the reanalysis data) leads to the largest improvement, while the temperature and radiation adjustments have only small effects.
When forced by this dataset, the CLM3 reproduces many aspects of the long-term mean, annual cycle, interannual and decadal variations, and trends of streamflow for many large rivers (e.g., the Orinoco, Changjiang, Mississippi, etc.), although substantial biases exist. The simulated long-term-mean freshwater discharge into the global and individual oceans is comparable to 921 river-based observational estimates. Observed soil moisture variations over Illinois and parts of Eurasia are generally simulated well, with the dominant influence coming from precipitation. The results suggest that the CLM3 simulations are useful for climate change analysis. It is also shown that unrealistically low intensity and high frequency of precipitation, as in most model-simulated precipitation or observed time-averaged fields, result in too much evaporation and too little runoff, which leads to lower than observed river flows. This problem can be reduced by adjusting the precipitation rates using observed-precipitation frequency maps.
Mapping “At Risk” Snow in the Pacific Northwest
Authors: Nolin Anne W. , Daly Christopher 
Published: November 2006

Abstract
One of the most visible and widely felt impacts of climate warming is the change (mostly loss) of low-elevation snow cover in the midlatitudes. Snow cover that accumulates at temperatures close to the ice-water phase transition is at greater risk to climate warming than cold climate snowpacks because it affects both precipitation phase and ablation rates. This study maps areas in the Pacific Northwest region of the United States that are potentially at risk of converting from a snow-dominated to a rain-dominated winter precipitation regime, under a climate-warming scenario. A data-driven, climatological approach of snow cover classification is used to reveal these “at risk” snow zones and also to examine the relative frequency of warm winters for the region. For a rain versus snow temperature threshold of 0°C the at-risk snow class covers an area of about 9200 km2 in the Pacific Northwest region and represents approximately 6.5 km3 of water. Many areas of the Pacific Northwest would see an increase in the number of warm winters, but the impacts would likely be concentrated in the Cascade and Olympic Ranges. A number of lower-elevation ski areas could experience negative impacts because of the shift from winter snows to winter rains. The results of this study point to the potential for using existing datasets to better understand the potential impacts of climate warming.
Increased cervical dysplasia in intravenous cyclophosphamidetreated patients with SLE: a preliminary study
Authors: Bateman H , Yazici Y , Leff L , Peterson M , Paget S A 
Published: November 2006

To determine if intravenous cyclophosphamide (IV-C) causes an excess of cervical dysplasia and/or cancer in systemic lupus erythematosus (SLE) patients, a retrospective review was conducted. Patients with SLE who received IV-C between 1988–98 (study group) were compared with a group of SLE patients who had not received IV-C (control group). Of the 79 IV-C-treated SLE patients identified, we excluded 18 because of absence of pertinent data. We found 10 cases of cervical dysplasia in the remaining 61 patients, compared to 2 in 49 non-exposed patients (P < 0.04). Comparison of the two groups revealed no difference in: mean years of disease duration, months of follow-up and age. The non-exposed patients were more likely to be on estrogen and hydroxychloroquine but less often on steroids and azathioprine. The study group with and without dysplasia were assessed; we found no difference in the mean, or total IV-C dose, smoking and estrogen use. There was a significant decrease in time to dysplasia in those, given IV-C, with previous dysplasia compared to those without. These preliminary data suggests that IV-C causes an increased number of abnormal Papanicolaou (Pap) smears in SLE patients, particularly those with previous dysplasia.
Gender and nitric oxide-mediated vasodilation in humans
Authors: Dietz N M 
Published: November 2006

Background: We compared forearm vasodilator responses between females and males after administration of compounds that stimulate nitric oxide (NO) release, act as NO donors, or are NO independent. Methods and results: We studied nine premenopausal females and nine age-matched males. Forearm blood flow (FBF) was measured with plethysmography. Graded doses of the endothelial dependent vasodilators acetylcholine and bradykinin and the endothelial-independent vasodilator sodium nitroprusside were given via a brachial artery catheter to the non-dominant arm. Reactive hyperemia was measured as an index of NO-independent vasodilation. In females estradiol levels were greater, and serum triglycerides were lower, but cholesterol was similar to that of males. FBF responses to all doses of the three drugs were ' 30% less in females. Females had smaller forearms and lower peak FBF during reactive hyperemia. Blood flow responses to the drugs as a fraction of the peak reactive hyperemia values were similar in females and males. In the females, but not in the males, FBF responses to all three drugs and reactive hyperemia correlated with estradiol levels. Conclusions: The smaller FBF responses in females were likely due to smaller forearm volume and muscle mass. Estradiol levels are associated with both NO-mediated and non-NO-mediated dilator responses in females.
Anti-endothelial cell IgG fractions from systemic lupus erythematosus patients bind to human endothelial cells and induce a pro-adhesive and a pro-infiammatory phenotype in vitro
Authors: Papa N Del , Raschi E , Moroni G , Panzeri P , Borghi M O , Ponticelli C , Tincani A , Balestrieri G , Meroni P L 
Published: November 2006

Affinity purified immunoglobulin G (IgG) fractions from systemic lupus erythematosus (SLE) patients positive for anti-endothelial cell antibodies (AECA) bind human umbilical vein endothelial cell (HUVEC) monolayers. In vitro incubation of serial protein concentrations of SLE AECA IgG induces a dose-dependent endothelial activation: i) increase of functional adhesion of the monocytic cell line U937; ii) upregulation of E-Selectin, ICAM-1, VCAM-1 expression evaluated by a cell solid-phase enzyme linked immunoassay; and iii) increased secretion of interleukin (IL)-6 in the culture supernatants. Control experiments carried out with HUVEC monolayers incubated with IgG fractions from normal healthy controls or from AECA negative SLE sera do not affect at all endothelial adhesion molecule expression or pro-inflammatory cytokine secretion. The AECA IgG effects are not related to both anti-phospholipid or anti-DNA activities. Taken together the findings suggest that these autoantibodies might be important in recruiting and in activating mononuclear leukocytes responsible for vessel wall infiltration and raise the possibility that AECA might display a pathogenic role in SLE vessel damage.
A Combined Treatment Approach for Adults With ADHD—Results of an Open Study of 43 Patients
Authors: Rostain Anthony L. , Ramsay J. Russell 
Published: November 2006

Objective: Increasing numbers of adults are seeking treatment for ADHD. Pharmacotherapy is well established as the first line treatment for adult ADHD, although medications alone may be insufficient treatment for the myriad problems experienced by these patients. Few studies have examined the clinical outcomes of a combination of pharmacotherapy and psychotherapy for this clinical population. The purpose of the present study is to examine the potential effectiveness of the combination of pharmacotherapy and cognitive-behavior therapy modified to treat adult patients diagnosed with ADHD. Method: Forty-three adults who underwent a structured diagnostic assessment for ADHD complete 6 months of combined treatment. Treatment outcome is assessed by comparing pre- and posttreatment measures of ADHD symptoms, comorbid symptoms, and ratings of overall functioning. Results/Conclusion: Results indicate that combined treatment is associated with significant improvements on all clinical measures. Limitations of the study design and directions for future research are discussed.
Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling
Authors: Sin Sang-Hoon , Roy Debasmita , Wang Ling , Staudt Michelle R. , Fakhari Farnaz D. , Patel Dhavalkumar D. , Henry David , Harrington William J. , Damania Blossom A. , Dittmer Dirk P. 
Published: November 2006

AbstractThe antitumor potency of the mTOR inhibitor rapamycin (sirolimus) is the subject of intense investigations. Primary effusion lymphoma (PEL) appears as an AIDS-defining lymphoma and like Kaposi sarcoma has been linked to Kaposi sarcoma–associated herpesvirus (KSHV). We find that (1) rapamycin is efficacious against PEL in culture and in a murine xenograft model; (2) mTOR, its activator Akt, and its target p70S6 kinase are phosphorylated in PEL; (3) rapamycin inhibits mTOR signaling as determined by S6 phosphorylation; (4) KSHV transcription is unaffected; (5) inhibition of IL-10 signaling correlates with drug sensitivity; and (6) addition of exogenous IL-10 or IL-6 can reverse the rapamycin growth arrest. This validates sirolimus as a new treatment option for PEL.
Pathologic consequences of STAT3 hyperactivation by IL-6 and IL-11 during hematopoiesis and lymphopoiesis
Authors: Jenkins Brendan J. , Roberts Andrew W. , Greenhill Claire J. , Najdovska Meri , Lundgren-May Therese , Robb Lorraine , Grail Dianne , Ernst Matthias 
Published: November 2006

AbstractWe have previously demonstrated that STAT3 hyperactivation via the interleukin 6 (IL-6) cytokine family receptor gp130 in gp130Y757F/Y757F mice leads to numerous hematopoietic and lymphoid pathologies, including neutrophilia, thrombocytosis, splenomegaly, and lymphadenopathy. Because IL-6 and IL-11 both signal via a gp130 homodimer, we report here a genetic approach to dissect their individual roles in these pathologies. Neutrophilia and thrombocytosis were absent in gp130Y757F/Y757F mice lacking either IL-6 (gp130Y757F/Y757F: IL-6−/−) or the IL-11 receptor α subunit (gp130Y757F/Y757F: IL-11Rα1−/−), and this was associated with a normalized bone marrow compartment. The elevated myelopoiesis and megakaryopoiesis in bone marrow of gp130Y757F/Y757F mice was attributable to an increase by either IL-6 or IL-11 in the STAT3-driven impairment of transforming growth factor β (TGF-β) signaling, which is a suppressor of these lineages. In contrast, the absence of IL-6, but not IL-11 signaling, prevented the splenomegaly, abnormal lymphopoiesis, and STAT3 hyperactivation in lymphoid organs of gp130Y757F/Y757F mice. Furthermore, hyperactivation of STAT3 in lymphoid organs was associated with increased expression of IL-6Rα, and IL-6Rα expression was reduced in gp130Y757F/Y757F: Stat3+/− mice displaying normal levels of STAT3 activity. Collectively, these data genetically define distinct roles of IL-6 and IL-11 in driving pathologic hematopoietic and lymphoid responses mediated by STAT3 hyperactivation.
Is FKBP5 a genetic marker of affective psychosis? A case control study and analysis of disease related traits
Authors: Gawlik Micha , Moller-Ehrlich Kerstin , Mende Meinhard , Jovnerovski Michael , Jung Sven , Jabs Burkhard , Knapp Michael , Stoeber Gerald 
Published: November 2006

Abstract

Background
A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as an important pathogenic factor in depression. Genetic variants of FKBP5, a protein of the HPA system modulating the glucocorticoid receptor, have been reported to be genetically associated with improved response to medical treatment and an increase of depressive episodes.

Methods
We examined three single nucleotide polymorphisms (SNPs) in FKBP5, rs4713916 in the proposed promoter region, rs1360780 in the second intron and rs3800373 in the 3'-untranslated region (3'-UTR), in a case-control study of Caucasian origin (affective psychosis: n = 248; controls: n = 188) for genetic association and association with disease related traits.

Results
Allele and genotype frequencies of rs4713916, rs1360780 and rs3800373 were not significantly different between cases and controls. Two three-locus haplotypes, G-C-T and A-T-G, accounted for 86.2% in controls. Odds ratios were not increased between cases and controls, except the rare haplotype G-C-G (OR 6.81), representing 2.1% of cases and 0.3% of controls. The frequency of rs4713916AG in patients deviated from expected Hardy-Weinberg equilibrium, the genotype AA at rs4713916 in monopolar depression (P = 0.011), and the two-locus haplotype rs1360780T – rs3800373T in the total sample (overall P = 0.045) were nominally associated with longer continuance of disease.

Conclusion
Our data do not support a significant genetic contribution of FKBP5 polymorphisms and haplotypes to affective psychosis, and the findings are inconclusive regarding their contribution to disease-related traits.
Qualitative evaluation of a form for standardized information exchange between orthopedic surgeons and occupational physicians
Authors: Faber Elske , Burdorf Alex , van Staa Anne Loes , Miedema Harald S , Verhaar Jan AN 
Published: November 2006

AbstractBackgroundBoth occupational physicians and orthopedic surgeons can be involved in the management of work relevant musculoskeletal disorders. These physicians hardly communicate with each other and this might lead to different advices to the patient. Therefore, we evaluated a standardized information exchange form for the exchange of relevant information between the orthopedic surgeon and the occupational physician. The main goals of this qualitative study are to evaluate whether the form improved information exchange, whether the form gave relevant information, and to generate ideas to further improve this information exchange.MethodsThe information exchange form was developed in two consensus meetings with five orthopedic surgeons and five occupational physicians. To evaluate the information exchange form, a qualitative evaluation was set up. Structured telephone interviews were undertaken with the patients, interviews with the physicians were face-to-face and semi-structured, based on a topic list. These interviews were recorded and literally transcribed. Each interview was analyzed separately in Atlas-Ti.ResultsThe form was used for 8 patients, 7 patients agreed to participate in the qualitative evaluation. All three orthopedic surgeons involved and three of the six involved occupational physicians agreed to be interviewed. The form was transferred to 4 occupational physicians, the other 3 patients recovered before they visited the occupational physician. The information on the form was regarded to be useful. All orthopedic surgeons agreed that the occupational physician should take the initiative. Most physicians felt that the form should not be filled out for each patient visiting an orthopedic surgeon, but only for those patients who do not recover as expected. Orthopedic surgeons suggested that a copy of the medical information provided to the general practitioner could also be provided to occupational physicians.ConclusionThe information exchange form was regarded to be useful and could be used in practice. The occupational physician should take the initiative for using this form and most physicians felt the information should only be exchanged for patients who do not recover as expected. That means that the advantage of giving information early in the treatment is lost.