bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disparities in medical care among commercially insured patients with newly diagnosed breast cancer
Authors: Short Louise J. , Fisher Maxine D. , Wahl Peter M. , Kelly Monique B. , Lawless Grant D. , White Sandra , Rodriguez Nancy A. , Willey Vincent J. , Brawley Otis W. 
Published: October 2009

AbstractBACKGROUND:African‐American women have increased breast cancer mortality compared with white women. Diagnostic and treatment gaps may contribute to this disparity.METHODS:In this retrospective, longitudinal cohort study, Southern US health plan claims data and linked medical charts were used to identify racial disparities in the diagnoses, treatment, and mortality of commercially insured women with newly diagnosed breast cancer. White women (n = 476) and African‐American women (n = 99) with newly diagnosed breast cancer were identified by breast cancer claims codes (International Classification of Diseases, Ninth Revision, Clinical Modification codes 174, 233.0, 238.3, and 239.3) between January 2000 and December 2004. Race, diagnoses (breast cancer stage, estrogen/progesterone receptor [ER/PR]‐positive status), treatment (breast‐conserving surgery, antiestrogen therapy, and chemotherapy interruption or reduction), and all‐cause mortality were assessed from medical charts. Multivariate regression analyses were adjusted for age, geography, and socioeconomic status to test the association of race with diagnoses/treatment.RESULTS:White women were older (P < .001) and had higher rates of diagnosis at stage 0/I (55.2% vs 38.4%; P < .05) than African‐American women. More white women had positive ER/PR status (75% vs 56% African‐American; P = .001) and received antiestrogen therapy if they were positive (37.2% vs 27.3% African‐American; P < .001). White women received slightly more breast‐conserving surgery and chemotherapy dose modification than African‐American women (P value nonsignificant). African‐American women had a higher mortality rate (8.1%) than white women (3.6%; P = .06). In adjusted analyses, African‐American women were diagnosed at later stages (odds ratio, 1.71; P = .02), and white women received more antiestrogen therapy (odds ratio, 2.1; P = .03).CONCLUSIONS:Disparities in medical care among patients with newly diagnosed breast cancer were evident between African‐American women and white women despite health plan insurance coverage. Interventions that address the gaps identified are needed. Cancer 2010. © 2010 American Cancer Society.
Racial differences in treatment and outcomes among patients with early stage bladder cancer
Authors: Hollenbeck Brent K. , Dunn Rodney L. , Ye Zaojun , Hollingsworth John M. , Lee Cheryl T. , Birkmeyer John D. 
Published: October 2009

AbstractBACKGROUND:Black patients are at greater of risk of death from bladder cancer than white patients. Potential explanations for this disparity include a more aggressive phenotype and delays in diagnosis resulting in higher stage disease. Alternatively, black patients may receive a lower quality of care, which may explain this difference.METHODS:Using Surveillance, Epidemiology, and End Results (SEER)‐Medicare data for the years from 1992 through 2002, the authors identified patients with early stage bladder cancer. Multivariate models were fitted to measure relations between race and mortality, adjusting for differences in patients and treatment intensity. Next, shared‐frailty proportional hazards models were fitted to evaluate whether the disparity was explained by differences in the quality of care provided.RESULTS:Compared with white patients (n = 14,271), black patients (n = 342) were more likely to undergo restaging resection (12% vs 6.5%; P < .01) and urine cytologic evaluation (36.8% vs 29.7%; P < .01), yet they received fewer endoscopic evaluations (4 vs 5; P < .01). The use of aggressive therapies (cystectomy, systemic chemotherapy, radiation) was found to be similar among black patients and white patients (12% vs 10.2%, respectively; P = .31). Although black patients had a greater risk of death compared with white patients (hazards ratio [HR], 1.23; 95% confidence interval [95% CI], 1.07‐1.42), this risk was attenuated only modestly after adjusting for differences in treatment intensity and provider effects (HR, 1.22; 95% CI, 1.06‐1.42).CONCLUSIONS:Although differences in initial treatment were evident, they did not appear to be systematic and had unclear clinical significance. Whereas black patients are at greater risk of death, this disparity did not appear to be caused by differences in the intensity or quality of care provided. Cancer 2010. © 2010 American Cancer Society.
A phase 2 clinical trial of nab‐paclitaxel in previously treated and chemotherapy‐naive patients with metastatic melanoma
Authors: Hersh Evan M. , O'Day Steven J. , Ribas Antoni , Samlowski Wolfram E. , Gordon Michael S. , Shechter Deganit E. , Clawson Alicia A. , Gonzalez Rene 
Published: October 2009

AbstractBACKGROUND:nab‐Paclitaxel (ABI‐007, Abraxane), a 130‐nM, albumin‐bound (nab) particle form of Cremophor‐free paclitaxel, is approved for metastatic breast cancer. In the current study, the efficacy and safety of nab‐paclitaxel were evaluated in previously treated and chemotherapy‐naive patients with metastatic melanoma (MM).METHODS:Patients with histologically or cytologically confirmed, measurable MM were enrolled. nab‐Paclitaxel was administered intravenously weekly for 3 of 4 weeks at a dose of 100 mg/m2 (in previously treated patients) or 150 mg/m2 (in chemotherapy‐naive patients).RESULTS:Thirty‐seven patients were treated in each cohort. The response rate was 2.7% in the previously treated cohort and 21.6% in the chemotherapy‐naive cohort; the response plus stable disease rate was 37.8% and 48.6% in the previously treated and chemotherapy‐naive cohorts, respectively. The median progression‐free survival (PFS) was 3.5 months and 4.5 months, and the median survival was 12.1 months and 9.6 months, respectively. The probability of being alive and free of disease progression at 6 months was 27% for the previously treated cohort and 34% for the chemotherapy‐naive cohort; the probability of surviving 1 year was 49% and 41%, respectively, for the previously treated and chemotherapy‐naive cohorts. Approximately 78% of the previously treated patients and 49% of the chemotherapy‐naive patients were treated without dose reduction. Eight (22%) chemotherapy‐naive patients discontinued therapy because of toxicities. Drug‐related toxicities included grade 3 to 4 (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) neuropathy, alopecia, neutropenia, and fatigue.CONCLUSIONS:nab‐Paclitaxel was found to be well tolerated and demonstrated activity in both previously treated and chemotherapy‐naive patients with MM. The response rate, PFS, and survival compared favorably with current standard dacarbazine therapy and combination therapies for melanoma. nab‐Paclitaxel therapy of MM should be investigated further in controlled clinical trials. Cancer 2010. © 2010 American Cancer Society.
Complications After Surgery in Hemodialysis Patients: A Comparison Between Diabetic and Non‐Diabetic Patients
Authors: Shimoyama Yoko , Nakamura Norio , Kawaguchi Toshiaki , Okumura Ken 
Published: October 2009

AbstractBACKGROUNDThe number of hemodialysis (HD) patients, especially the number of HD patients who need this treatment due to diabetic nephropathy, is markedly increasing. We investigated the types and numbers of surgeries and post‐surgery complications in HD patients, and compared data between patients with and without diabetes mellitus (DM).METHODSA total of 188 HD patients who had undergone surgery (except ophthalmological surgery) at the Hirosaki University Hospital from 1998 to 2004 were entered into the present study. The types and numbers of surgeries, the complications after surgery, and the laboratory data before surgery were taken from the medical records. We compared these data between DM and non‐DM patients.RESULTSIn the DM patients, the number of surgeries involving the vascular system were higher than in non‐DM patients. Of complications after surgery, congestion was the most frequently observed complication in both the DM and the non‐DM patients. Infection and delayed wound healing were more frequently observed in the DM patients. In the analysis of laboratory data before surgery, the serum total protein and potassium concentrations in patients with complications after surgery were lower than in patients without complications.CONCLUSIONSThese results suggest that, to prevent complications post‐surgery, we should pay special attention to vascular diseases in HD patients with diabetes and carefully manage the nutritional conditions in HD patients.
Sequence variation in IGF1R is associated with differences in insulin levels in nondiabetic Old Order Amish
Authors: Naj Adam C. , Kao Wen‐Hong L. , O'Connell Jeffrey R. , Mitchell Braxton D. , Silver Kristi D. 
Published: October 2009

AbstractBackgroundInsulin growth factor‐1 receptor (IGF1R) encodes the insulin‐like growth factor 1 receptor, a transmembrane tyrosine kinase receptor located on chromosome 15q26.3, in a region of linkage (LOD = 2.53, P = 0.00032) to Insulin30 on an OGTT in the Old Order Amish. Mouse models with beta‐cell‐specific deficiency of IGF1R demonstrate defects in glucose‐stimulated insulin secretion.MethodsTo test the hypothesis that genetic variation in IGF1R is associated with impaired insulin secretion, we genotyped 54 SNPs in 778 nondiabetic subjects from the AFDS who had undergone OGTTs and tested them for association with ln Insulin30 and ISI.ResultsNo individual SNPs were significantly associated with ln Insulin30 or ISI using a multiple hypothesis testing adjusted P < 0.002. Tests of association of 4‐SNP haplotypes constructed by a windowing approach revealed an association of the CTTG‐variant of a 4‐SNP haplotype found in intron 20 (rs1784195–rs2715439–rs8034284–rs12440962) with lower ISI levels (β = 0.18, SE(β) = 0.05, P = 0.001).ConclusionsSequence variation in IGF1R may influence insulin secretory function, although further studies in other populations will be needed to confirm these findings. Copyright © 2009 John Wiley & Sons, Ltd.
Elephant in the room? The methodological implications for public health research of performance‐enhancing drugs derived from the illicit market
Authors: Evans‐Brown Michael , Kimergård Andreas , McVeigh Jim 
Published: October 2009

Abstract‘All scientific work is incomplete—whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time.’1Copyright © 2009 John Wiley & Sons, Ltd.
The metalloendopeptidase gene Pitrm1 is regulated by hedgehog signaling in the developing mouse limb and is expressed in muscle progenitors
Authors: Town Liam , McGlinn Edwina , Fiorenza Salvatore , Metzis Vicki , Butterfield Natalie C. , Richman Joy M. , Wicking Carol 
Published: October 2009

AbstractPitrm1 is a zinc metalloendopeptidase that has been implicated in Alzheimer's disease and mitochondrial peptide degradation, but to date no major role in embryonic development has been documented. In a screen for genes regulated by hedgehog signaling in the mouse limb, we showed that expression of Pitrm1 is upregulated in response to loss of the Gli3 transcription factor. Here we confirm spatial changes in Pitrm1 expression in the Gli3 mutant mouse limb and examine Pitrm1 expression in Shh null and Ptch1 conditional deletion mouse mutants. In wild‐type mice, Pitrm1 is expressed in a number of developing tissues known to be patterned by Sonic hedgehog, including the limbs, face, cortex, hippocampus, cerebellum, tectum, sub‐mandibular gland, lung, genital tubercle, hair follicles, and the enamel knot of the teeth. Additionally, Pitrm1 is expressed in Pax3‐expressing myoblast progenitors in the limb, the dermomyotome, and developing muscles of the face and torso. Developmental Dynamics 238:3175–3184, 2009. © 2009 Wiley‐Liss, Inc.
Planar cell polarity effector gene Fuzzy regulates cilia formation and Hedgehog signal transduction in mouse
Authors: Heydeck Westley , Zeng Huiqing , Liu Aimin 
Published: October 2009

AbstractPrecise planar cell polarity (PCP) is critical for the development of multiple organ systems in animals. A group of core‐PCP proteins are recognized to play crucial roles in convergent extension and other PCP‐related processes in mammals. However, the functions of another group of PCP‐regulating proteins, the PCP‐effector proteins, are yet to be fully studied. In this study, the generation and characterization of a mouse mutant for the PCP effector gene Fuzzy (Fuz) is reported. Fuz homozygous mutants are embryonically lethal, with multiple defects including neural tube defects, abnormal dorsal/ventral patterning of the spinal cord, and defective anterior/posterior patterning of the limb buds. Fuz mutants also exhibit abnormal Hedgehog (Hh) signaling and inefficient proteolytic processing of Gli3. Finally, a significant decrease in cilia was found in Fuz homozygous mutants. In conclusion, Fuz plays an important role in cilia formation, Hh signal transduction, and embryonic development in mammals. Developmental Dynamics 238:3035–3042, 2009. © 2009 Wiley‐Liss, Inc.
Postnatal lung development of rhesus monkey airways: Cellular expression of Clara cell secretory protein
Authors: Coppens John T. , Plopper Charles G. , Murphy Shannon R. , Van Winkle Laura S. 
Published: October 2009

AbstractClara cell secretory protein (CCSP) is a protective lung protein that is believed to have antioxidant, immunomodulatory, and anticarcinogenic properties. Evidence suggests that CCSP is involved in mitigating many lung disease states during development including asthma. This study's rationale is to define the distribution and abundance of CCSP in the airway epithelium of the rhesus monkey during postnatal lung development using carefully controlled site‐specific morphometric approaches in defined airway regions. Immunoreactive CCSP was found in nonciliated cells and mucous cells, including glands, throughout the airway epithelium at all ages, with proximal and mid‐level airways having the highest labeling. Overall airway CCSP levels were low at 1 week and 1 month, doubled between 1 and 3 months, and changed little from 3 months to 3 years. Thus, the critical developmental window for CCSP expression to reach adult levels in the rhesus conducting airways occurs between 1 and 3 months of age. Developmental Dynamics 238:3016–3024, 2009. © 2009 Wiley‐Liss, Inc.
A co‐dependent requirement of xBcl9 and Pygopus for embryonic body axis development in Xenopus
Authors: Kennedy Mark W. , Cha Sang‐Wook , Tadjuidje Emmanuel , Andrews Phillip G. , Heasman Janet , Kao Kenneth R. 
Published: October 2009

AbstractThe Wnt/β‐catenin transcriptional activation complex requires the adapter protein Pygopus (Pygo), which links the basal transcription machinery to β‐catenin, by its association with legless (Lgs)/ B‐cell lymphoma‐9 (Bcl9). Pygo was shown to be required for development in vertebrates, but the role of Lgs/Bcl9 is unknown. We identified an amphibian orthologue of Lgs/Bcl9, XBcl9, which interacted biochemically with Xβ‐catenin and XPygo2. The body axis promoting ability of Xβ‐catenin was diminished when residues required for its interaction with XBcl9 were mutated. In blastula embryos, XBcl9 was transiently preferentially expressed in nuclei of dorsoanterior cells and ectopically expressed XBcl9 required XPygo2 to localize to nuclei. Furthermore, while neither XBcl9 nor XPygo2 alone affected development when ectopically expressed, both were required to induce supernumerary axis and dorsal gene activation. Like XPygo2, depletion of maternal XBcl9 alone caused dorsal defects. These results indicated an essential role of the Pygo‐Bcl9 duet in vertebrate body axis formation. Developmental Dynamics 239:271–283, 2010. © 2009 Wiley‐Liss, Inc.
Dynamic patterning at the pylorus: Formation of an epithelial intestine–stomach boundary in late fetal life
Authors: Li Xing , Udager Aaron M. , Hu Chunbo , Qiao Xiaotan T. , Richards Neil , Gumucio Deborah L. 
Published: October 2009

AbstractIn the adult mouse, distinct morphological and transcriptional differences separate stomach from intestinal epithelium. Remarkably, the epithelial boundary between these two organs is literally one cell thick. This discrete junction is established suddenly and precisely at embryonic day (E) 16.5, by sharpening a previously diffuse intermediate zone. In the present study, we define the dynamic transcriptome of stomach, pylorus, and intestinal tissues between E14.5 and E16.5. We show that establishment of this boundary is concomitant with the induction of over a thousand genes in intestinal epithelium, and these gene products provide intestinal character. Hence, we call this process intestinalization. We identify specific transcription factors (Hnf4γ, Creb3l3, and Tcfec) and examine signaling pathways (Hedgehog and Wnt) that may play a role in this process. Finally, we define a unique expression domain at the pylorus itself and detect novel pylorus‐specific patterns for the transcription factor Gata3 and the secreted protein nephrocan. Developmental Dynamics 238:3205–3217, 2009. © 2009 Wiley‐Liss, Inc.
Focal electroporation in ovo
Authors: Simkin J. E. , McKeown S. J. , Newgreen D. F. 
Published: October 2009

AbstractGene expression fields in embryogenesis are spatially precise and often small, so experimental gene expression often requires similar spatial definition. For in ovo electroporation, typically a gene construct is injected into a natural body cavity in the embryo prior to electroporation. Limited control of the size and location of the electroporated field can be obtained by varying electrode placement and geometry, and by altering the miscibility and viscosity of the construct vehicle but it is difficult to tightly constrain electroporation to small regions. Electroporation of different constructs in close proximity has not been possible. We show that loading the construct into an agarose bead, which is then microsurgically implanted, allows for focal electroporation. Different constructs can be electroporated in close proximity by emplacing several agarose beads. This technique is simple, cheap, rapid, and requires no more specialised equipment than that required for conventional in ovo electroporation. Developmental Dynamics 238:3152–3155, 2009. © 2009 Wiley‐Liss, Inc.
Antigen‐specific Treg impair CD8+ T‐cell priming by blocking early T‐cell expansion
Authors: Chappert Pascal , Leboeuf Marylène , Rameau Philippe , Lalfer Mélanie , Desbois Sabine , Liblau Roland S. , Danos Olivier , Davoust Jean M. , Gross David‐Alexandre 
Published: October 2009

AbstractFoxp3+ Treg are crucial for the maintenance of self‐tolerance and have been shown to control CD8+ T‐cell effector functions. In addition, Treg are thought to control the priming of CD8+ T cells, which recognize the same antigens as Treg. Taking advantage of our model of peripheral tolerance induction to influenza hemagglutinin (HA) after HA gene transfer, we found that HA‐specific Treg suppress antigen‐linked CTL responses through early blockade of CD8+ T‐cell expansion. Confronted with their cognate antigen, Treg expand more rapidly than CD8+ T cells and are highly suppressive only during the initial stages of immune priming. They nullify HA‐specific CD8+ T‐cell responses, local inflammatory responses and rejection of HA transduced cells. When HA gene transfer is performed with extensive tissue inflammation, HA‐specific Treg are less effective but still reduce the frequency of newly primed HA‐specific CD8+ T cells and the ensuing frequency of memory CD8+ T cells. Our results demonstrate that Treg control CTL priming in an antigen‐specific manner at the level of T‐cell expansion, highlighting how self‐reactive Treg could prevent the induction of autoimmune responses through selective blockade of autoreactive T‐cell proliferation.
Micro‐RNA‐155 inhibits IFN‐γ signaling in CD4+ T cells
Authors: Banerjee Arnob , Schambach Felix , DeJong Caitlin S. , Hammond Scott M. , Reiner Steven L. 
Published: October 2009

AbstractMicro‐RNA (miR) are increasingly recognized as critical regulators of tissue‐specific patterns of gene expression. CD4+ T cells lacking miR‐155, for example, exhibit bias towards Th2 differentiation, indicating that the absence of individual miR could alter CD4+ T‐cell differentiation. We now show that miR‐155 is induced upon T‐cell activation and that it promotes Th1 differentiation when over‐expressed in activated CD4+ T cells. Antagonism of miR‐155 leads to induction of IFN‐γ receptor α‐chain (IFN‐γRα, and a functional miR‐155 target site is identified within the 3′ untranslated region of IFN‐γRα. These results identify IFN‐γRα as a second miR‐155 target in T cells and suggest that miR‐155 contributes to Th1 differentiation in CD4+ T cells by inhibiting IFN‐γ signaling.
BCR‐induced superoxide negatively regulates B‐cell proliferation and T‐cell‐independent type 2 Ab responses
Authors: Richards Sabrina M. , Clark Edward A. 
Published: October 2009

AbstractSuperoxide and its derivatives have been implicated as secondary messenger molecules that influence signaling cascades in non‐phagocytes. B lymphocytes produce superoxide after BCR ligation. We found that these ROS regulate B‐cell signaling and entry into the cell cycle. B cells from mice deficient in the gp91phox subunit of the NADPH oxidase complex are unable to generate ROS after BCR ligation. However, after BCR stimulation, more gp91phox KO B cells enter the G1 stage of the cell cycle and proliferate than WT B cells. BCR ligation leads to a more rapid decrease in p27Kip1 levels in gp91phox KO B cells. Gp91phox KO mice display enhanced T‐cell‐independent type 2, but normal T‐dependent Ab responses. ROS‐dependent regulation of BCR‐induced proliferation may help modulate the size of the humoral response to T‐cell‐independent type 2 Ag immunization.
Leishmania donovani‐induced expression of signal regulatory protein α on Kupffer cells enhances hepatic invariant NKT‐cell activation
Authors: Beattie Lynette , Svensson Mattias , Bune Alison , Brown Najmeeyah , Maroof Asher , Zubairi Soombul , Smith Katharine R. , Kaye Paul M. 
Published: October 2009

AbstractSignal regulatory protein α (SIRPα) and its cognate ligand CD47 have been documented to have a broad range of cellular functions in development and immunity. Here, we investigated the role of SIRPα–CD47 signalling in invariant NKT (iNKT) cell responses. We found that CD47 was required for the optimal production of IFN‐γ from splenic iNKT cells following exposure to the αGalCer analogue PBS‐57 and in vivo infection of mice with Leishmania donovani. Surprisingly, although SIRPα was undetectable in the liver of uninfected mice, the hepatic iNKT‐cell response to infection was also impaired in CD47−/− mice. However, we found that SIRPα was rapidly induced on Kupffer cells following L. donovani infection, via a mechanism involving G‐protein‐coupled receptors. Thus, we describe a novel amplification pathway affecting cytokine production by hepatic iNKT cells, which may facilitate the breakdown of hepatic tolerance after infection.