bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nucleolar Sik-Similar Protein (Sik-SP) Is Required for the Maintenance of Uterine Estrogen Signaling Mechanism Via ERα
Authors: Chung Daesuk , Gao Fei , Ostmann Alicia , Hou Xiaonan , Das Sanjoy K. 
Published: January 2012

AbstractSik-similar protein (Sik-SP), a small nucleolar ribonucleoprotein, has been shown to be primarily involved in ribosome biogenesis. However, its role in the hormone-directed nuclear receptor signaling is largely unknown. Here, we provide novel evidence that Sik-SP is required for appropriate regulation of estrogen receptor (ER)α-mediated estradiol-17β (E2)-dependent uterine physiologic responses in mice. Studies by Western blotting using the newly developed antibodies for Sik-SP showed that this protein is up-regulated in both the ovariectomized wild-type and ERα null uteri by E2. Immunohistochemical analyses in uterine sections showed that this protein is induced in the epithelial and stromal cells. Coimmunoprecipitation studies revealed that E2 directs molecular interaction between Sik-SP and ERα. Furthermore, gel-mobility shift and chromatin immunoprecipitation analyses provided evidence that Sik-SP is recruited with ERα to estrogen-responsive uterine gene promoters. Overexpression of Sik-SP in vitro demonstrated a role for Sik-SP in cellular growth and viability. In a primary uterine epithelial-stromal coculture system, E2 exhibited early induction of Sik-SP in both the epithelial and stromal cells. Interestingly, suppression of Sik-SP in this coculture model, for the stromal but not epithelial cells, caused perturbation of E2-dependent proliferation in the epithelial cell layer. Similarly, in vivo uterine suppression of Sik-SP also caused inhibition of epithelial cell proliferation and aberrant prolongation of water imbibition in the late phase by E2. Finally, studies showed that Sik-SP is physiologically important during the onset of implantation by E2. In conclusion, Sik-SP, an early E2-responsive nucleolar protein, is necessary to induce E2-dependent ERα-mediated appropriate physiologic responses in the uterus.
Multiattribute One-Switch Utility
Authors: Tsetlin Ilia , Winkler Robert L. 
Published: January 2012

The one-switch property states that the preference between any two lotteries switches at most once as wealth increases. Working within the expected utility framework, we extend the one-switch notion to the multiattribute case and identify the families of multiattribute utility functions that are one-switch. We then show that all multiattribute one-switch utility functions can be approximated by a sum of two multiattribute exponential utilities (sumex utility). Finally, we discuss how the one-switch property, when appropriate, can simplify the assessment of multiattribute utility. This paper was accepted by Peter Wakker, decision analysis.
Rational Herding in Microloan Markets
Authors: Zhang Juanjuan , Liu Peng 
Published: January 2012

Microloan markets allow individual borrowers to raise funding from multiple individual lenders. We use a unique panel data set that tracks the funding dynamics of borrower listings on Prosper.com, the largest microloan market in the United States. We find evidence of rational herding among lenders. Well-funded borrower listings tend to attract more funding after we control for unobserved listing heterogeneity and payoff externalities. Moreover, instead of passively mimicking their peers (irrational herding), lenders engage in active observational learning (rational herding); they infer the creditworthiness of borrowers by observing peer lending decisions and use publicly observable borrower characteristics to moderate their inferences. Counterintuitively, obvious defects (e.g., poor credit grades) amplify a listing's herding momentum, as lenders infer superior creditworthiness to justify the herd. Similarly, favorable borrower characteristics (e.g., friend endorsements) weaken the herding effect, as lenders attribute herding to these observable merits. Follow-up analysis shows that rational herding beats irrational herding in predicting loan performance. This paper was accepted by Pradeep Chintagunta, marketing.
Dynamics of Rate-of-Return Regulation
Authors: Nezlobin Alexander , Rajan Madhav V. , Reichelstein Stefan 
Published: January 2012

Under rate-of-return regulation, a firm's product prices are constrained by the requirement that investors not earn more than an allowable return on the firm's assets. This paper examines the dynamic properties of the rate-of-return regulation process when the regulated firm periodically undertakes new capacity investments. Our analysis identifies prices that correspond to stationary values of the regulation process. It is shown that the underlying depreciation rules for property, plant, and equipment determine whether these stationary prices will be above, equal to, or below the long-run marginal cost of providing the regulated service. We provide conditions under which the rate-of-return regulation process is dynamically stable so that prices indeed converge to their stationary values. The overall efficiency of this regulation method is shown to depend on how well the applicable depreciation schedule matches the productivity pattern of the assets in use. This paper was accepted by Gérard P. Cachon, accounting.
Characteristics of Oral Mucosal Events Related to Bevacizumab Treatment
Authors: Gavrilovic Igor T. , Balagula Yevgeniy , Rosen Alyx C. , Ramaswamy Vijay , Dickler Maura N. , Dunkel Ira J. , Lacouture Mario E. 
Published: January 2012

Abstract

Background.
Bevacizumab, a monoclonal antibody targeting a vascular endothelial growth factor (VEGF) protein, has been reported to induce mucosal toxicities. However, the clinical characteristics of these particular toxicities have not been well characterized. We aimed at providing a detailed clinical description of signs and symptoms limited to the tongue mucosa in patients treated with bevacizumab.

Methods.
A retrospective review of medical records and clinical photographs was performed with specific attention to clinical presentation, evolution, associated symptoms, concomitant medications, and treatment methods.

Results.
In total, four patients presented to the dermatology service with clinical findings characterized by multifocal, erythematous circinate and serpiginous erosions on the dorsal tongue surrounded by white hyperkeratotic rims that were temporally related to bevacizumab therapy. Associated increased sensitivity to spicy foods was frequently observed.

Conclusion.
These characteristic clinical findings are consistent with geographic tongue. However, large prospective evaluations are necessary to confirm this potential relationship. If bevacizumab is indeed associated with geographic tongue, increased awareness may result in improved reporting and characterization of this particular adverse event.
Phase II Study of Gonadotropin-Releasing Hormone Analog for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
Authors: Cheng Yee Chung , Takagi Mariko , Milbourne Andrea , Champlin Richard E. , Ueno Naoto T. 
Published: January 2012

Abstract

Purpose.
Premature ovarian failure occurs in 40%–70% of patients who receive conventional chemotherapy alone. However, the incidence is higher, 70%–100%, in patients who undergo myeloablative chemotherapy with hematopoietic stem cell transplantation (HSCT). Gonadotropin-releasing hormone (GnRH) analogs, such as leuprolide, in a continuous-release formulation, may protect the ovaries from the gonadotoxic effects of chemotherapy. In non-HSCT settings, GnRH analogs have reduced the risk for premature ovarian failure to &lt;10%. We conducted a phase II clinical trial based on the hypothesis that giving leuprolide before conditioning chemotherapy in HSCT patients reduces premature ovarian failure incidence.

Patients and Methods.
Eligible patients were women aged ≤40 years who were HSCT candidates, were premenopausal, and had both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels ≤20 IU/L. Two 22.5-mg leuprolide doses were delivered in 3-month depot i.m. injections, the first within 2 months before HSCT. Patients were monitored for menstruation return, and ovarian function tests (FSH, LH, and estradiol) were done every 2 months starting 90 days after the last leuprolide dose.

Results.
Sixty eligible patients were enrolled, 59 underwent HSCT, and 44 were evaluable (median age, 25 years; median follow-up, 355 days). Only seven of 44 patients (16%) regained ovarian function. Of the 33 who received myeloablative regimens, six (18%) regained ovarian function. However, among the 11 who received nonmyeloablative regimens, only one (9%) regained ovarian function (p = .66).

Conclusion.
Leuprolide did not preserve ovarian function in patients who underwent HSCT using either myeloablative or nonmyeloablative regimens. Other measures that protect ovarian function need to be investigated.
Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone with or Without Radiotherapy in Primary Mediastinal Large B-Cell Lymphoma: The Emerging Standard of Care
Authors: Vassilakopoulos Theodoros P. , Pangalis Gerassimos A. , Katsigiannis Andreas , Papageorgiou Sotirios G. , Constantinou Nikos , Terpos Evangelos , Zorbala Alexandra , Vrakidou Effimia , Repoussis Panagiotis , Poziopoulos Christos , Galani Zacharoula , Dimopoulou Maria N. , Kokoris Stella I. , Sachanas Sotirios , Kalpadakis Christina , Dimitriadou Evagelia M. , Siakantaris Marina P. , Kyrtsonis Marie-Christine , Dervenoulas John , Dimopoulos Meletios A. , Meletis John , Roussou Paraskevi , Panayiotidis Panayiotis , Beris Photis , Angelopoulou Maria K. 
Published: January 2012

AbstractLearning ObjectivesAfter completing this course, the reader will be able to: Describe the effect of the addition of rituximab to standard CHOP chemotherapy on the outcome of patients with primary mediastinal large B-cell lymphoma.Explain potential changes in the use of radiotherapy and aggressive chemotherapy in the rituximab era.This article is available for continuing medical education credit at CME.TheOncologist.comMore aggressive treatment approaches (methotrexate, cytarabine, cyclophosphamide, vincristine, prednisone, and bleomycin [the MACOP-B regimen] or consolidation with high-dose therapy and autologous stem cell transplantation) have been considered to be superior to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with primary mediastinal large B-cell lymphoma (PMLBCL). Rituximab-CHOP (R-CHOP) is the standard of care for diffuse large B-cell lymphoma, whereas efficacy in PMLBCL has not been adequately confirmed.Patient and Methods.Seventy-six consecutive PMLBCL patients who received R-CHOP with or without radiotherapy (RT) were compared with 45 consecutive historical controls treated with CHOP with or without RT. Baseline characteristics of the two groups were balanced.Results.The rate of early treatment failure was much lower with R-CHOP with or without RT (9% versus 30%; p = .004). The 5-year freedom from progression rate after R-CHOP with or without RT was 81%, versus 48% for CHOP with or without RT (p &lt; .0001). The 5-year event-free survival rates were 80% and 47% (p &lt; .0001) and the 5-year overall and lymphoma-specific survival rates were 89% and 69% (p = .003) and 91% and 69% (p = .001), respectively, with only seven of 76 lymphoma-related deaths. Among R-CHOP responders, 52 of 68 received RT.Conclusions.Based on these results, most patients with PMLBCL appear to be cured by R-CHOP in 21-day cycles with or without RT, which could be the current standard of care. Therefore, the need for more aggressive treatment strategies is questionable unless high-risk patients are adequately defined. Further studies are required to establish the precise role of RT.
Long-Term Kidney Allograft Function and Survival in Prednisone-Free Regimens
Authors: Chhabra Darshika , Skaro Anton I. , Leventhal Joseph R. , Dalal Pranav , Shah Gaurav , Wang Edward , Gallon Lorenzo 
Published: January 2012

Summary

Background and objectives
The optimal maintenance immunosuppressive regimen to improve long-term renal allograft function and graft survival is yet to be determined.

Design, setting, participants, & measurements
This observational study prospectively compared tacrolimus/sirolimus with tacrolimus/mycophenolate mofetil in renal transplant recipients using a prednisone-free regimen with over 8.5 years of follow-up. Patients received methylprednisonlone and anti-IL2 receptor antagonist (Basiliximab) induction and were blindly randomized to either the tacrolimus/mycophenolate mofetil (n=45) or tacrolimus/sirolimus (n=37) groups. Outcome measures included patient and renal allograft survival, incidence of acute rejection, and estimated GFR.

Results
The tacrolimus/mycophenolate mofetil group compared with the tacrolimus/sirolimus group had overall better renal allograft survival (91% versus 70%, P=0.02); 13 patients (35.1%) in the tacrolimus/sirolimus group and 8 patients (17.8%) in the tacrolimus/mycophenolate mofetil group experienced biopsy-proven acute cellular rejection (P=0.07). By 3 months post-transplant, estimated GFR was significantly lower in the tacrolimus/sirolimus group compared with the tacrolimus/mycophenolate mofetil group (47.7 versus 59.6 ml/min per 1.73 m2, P=0.0002), and this trend persisted throughout the follow-up period. Also, the slope of decline in the tacrolimus/sirolimus group was significantly steeper than in the tacrolimus/mycophenolate mofetil group.

Conclusions
This study shows that, in a prednisone-free immunosuppressive regimen, long-term renal graft survival and function are significantly worse in the tacrolimus/sirolimus group than the tacrolimus/mycophenolate mofetil group. The synergistic nephrotoxic effect and higher acute rejection rates in the tacrolimus/sirolimus compared with the tacrolimus/mycophenolate mofetil group adversely affect graft survival.
Pharmacokinetics and Pharmacodynamics of Piperacillin-Tazobactam in 42 Patients Treated with Concomitant CRRT
Authors: Bauer Seth R. , Salem Charbel , Connor Michael J. , Groszek Joseph , Taylor Maria E. , Wei Peilin , Tolwani Ashita J. , Fissell William H. 
Published: January 2012

Summary

Background and objectives
Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today. This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions.

Design, setting, participants, & measurements
A multicenter prospective observational study in the intensive care units of two academic medical centers was performed, enrolling patients with AKI or ESRD receiving piperacillin-tazobactam while being treated with continuous renal replacement therapy. Pregnant women, children, and patients with end stage liver disease were excluded from enrollment. Plasma and continuous renal replacement therapy effluent samples were analyzed for piperacillin and tazobactam levels using HPLC. Pharmacokinetic and pharmacodynamic parameters were calculated using standard equations. Multivariate analyses were used to examine the association of patient and continuous renal replacement therapy characteristics with piperacillin pharmacokinetic parameters.

Results
Forty-two of fifty-five subjects enrolled had complete sampling. Volume of distribution (median=0.38 L/kg, intraquartile range=0.20 L/kg) and elimination rate constants (median=0.104 h−1, intraquartile range=0.052 h−1) were highly variable, and clinical parameters could explain only a small fraction of the large variability in pharmacokinetic parameters. Probability of target attainment for piperacillin was 83% for total drug but only 77% when the unbound fraction was considered.

Conclusions
There is significant patient to patient variability in pharmacokinetic/pharmacodynamic parameters in patients receiving continuous renal replacement therapy. Many patients did not achieve pharmacodynamic targets, suggesting that therapeutic drug monitoring might optimize therapy.
Incidence and Progression of Diabetic Retinopathy During 17 Years of a Population-Based Screening Program in England
Authors: Jones Colin D. , Greenwood Richard H. , Misra Aseema , Bachmann Max O. 
Published: January 2012

OBJECTIVE
To estimate the incidence of diabetic retinopathy in relation to retinopathy grade at first examination and other prognostic characteristics.

RESEARCH DESIGN AND METHODS
This was a dynamic cohort study of 20,686 people with type 2 diabetes who had annual retinal photography up to 14 times between 1990 and 2006. Cumulative and annual incidence rates were estimated using life tables, and risk factors for progression were identified using Cox regression analysis.

RESULTS
Of 20,686 patients without proliferative diabetic retinopathy (PDR) or sight-threatening maculopathy at their first retinal examination (baseline), 16,444 (79%) did not have retinopathy, 3,632 (18%) had nonproliferative retinopathy, and 610 (2.9%) had preproliferative retinopathy. After 5 years, few patients without retinopathy at baseline developed preproliferative retinopathy (cumulative incidence 4.0%), sight-threatening maculopathy (0.59%), or PDR (0.68%); after 10 years, the respective cumulative incidences were 16.4, 1.2, and 1.5%. Among those with nonproliferative (background) retinopathy at baseline, after 5 years 23% developed preproliferative retinopathy, 5.2% developed maculopathy, and 6.1% developed PDR; after 10 years, the respective cumulative incidences were 53%, 9.6%, and 11%. Patients with nonproliferative retinopathy at baseline were five times more likely to develop preproliferative, PDR, or maculopathy than those without retinopathy at baseline (adjusted hazard ratio 5.0 [95% CI 4.4–5.6]).

CONCLUSIONS
Few patients without diabetic retinopathy at the initial screening examination developed preproliferative retinopathy, PDR, or sight-threatening maculopathy after 5–10 years of follow-up. Screening intervals longer than a year may be appropriate for such patients.
Helicobacter pylori Infection Is Associated With an Increased Rate of Diabetes
Authors: Jeon Christie Y. , Haan Mary N. , Cheng Caroline , Clayton Erin R. , Mayeda Elizabeth R. , Miller Joshua W. , Aiello Allison E. 
Published: January 2012

OBJECTIVE
Chronic infections could be contributing to the socioeconomic gradient in chronic diseases. Although chronic infections have been associated with increased levels of inflammatory cytokines and cardiovascular disease, there is limited evidence on how infections affect risk of diabetes.

RESEARCH DESIGN AND METHODS
We examined the association between serological evidence of chronic viral and bacterial infections and incident diabetes in a prospective cohort of Latino elderly. We analyzed data on 782 individuals aged &gt;60 years and diabetes-free in 1998–1999, whose blood was tested for antibodies to herpes simplex virus 1, varicella virus, cytomegalovirus, Helicobacter pylori, and Toxoplasma gondii and who were followed until June 2008. We used Cox proportional hazards regression to estimate the relative incidence rate of diabetes by serostatus, with adjustment for age, sex, education, cardiovascular disease, smoking, and cholesterol levels.

RESULTS
Individuals seropositive for herpes simplex virus 1, varicella virus, cytomegalovirus, and T. gondii did not show an increased rate of diabetes, whereas those who were seropositive for H. pylori at enrollment were 2.7 times more likely at any given time to develop diabetes than seronegative individuals (hazard ratio 2.69 [95% CI 1.10–6.60]). Controlling for insulin resistance, C-reactive protein and interleukin-6 did not attenuate the effect of H. pylori infection.

CONCLUSIONS
We demonstrated for the first time that H. pylori infection leads to an increased rate of incident diabetes in a prospective cohort study. Our findings implicate a potential role for antibiotic and gastrointestinal treatment in preventing diabetes.
Glycemic Response and Attainment of A1C Goals Following Newly Initiated Insulin Therapy for Type 2 Diabetes
Authors: Nichols Gregory A. , Kimes Teresa M. , Harp Joyce B. , Kou Tzuyung Doug , Brodovicz Kimberly G. 
Published: January 2012

OBJECTIVE
To identify the characteristics associated with glycemic response to newly initiated insulin therapy.

RESEARCH DESIGN AND METHODS
We identified 1,139 type 2 diabetic patients who initiated insulin therapy between 1 January 2009 and 30 June 2010. Outcomes of interest were the proportion of patients achieving A1C &lt;7% and mean change in A1C within 3–9 months.

RESULTS
Mean A1C at insulin initiation was 8.2 vs. 9.2% among those who did and did not attain A1C &lt;7% (P &lt; 0.001). Within a mean of 5 months, 464 (40.7%) patients attained A1C &lt;7%. In multivariable analyses controlling for insulin regimen, dose, and oral agent use, preinsulin A1C was responsible for nearly all the explained variance in A1C change. Each one percentage point of preinsulin A1C reduced the probability of attaining &lt;7% by 26% (odds ratio 0.74 [95% CI 0.68–0.80]).

CONCLUSIONS
Insulin initiation at lower levels of A1C improves goal attainment and independently increases glycemic response.
Age Before Stage: Insulin Resistance Rises Before the Onset of Puberty
Authors: Jeffery Alison N. , Metcalf Brad S. , Hosking Joanne , Streeter Adam J. , Voss Linda D. , Wilkin Terence J. 
Published: January 2012

OBJECTIVE
Insulin resistance (IR) is associated with diabetes. IR is higher during puberty in both sexes, with some studies showing the increase to be independent of changes in adiposity. Few longitudinal studies have reported on children, and it remains unclear when the rise in IR that is often attributed to puberty really begins. We sought to establish from longitudinal data its relationship to pubertal onset, and interactions with age, sex, adiposity, and IGF-1.

RESEARCH DESIGN AND METHODS
The EarlyBird Diabetes study is a longitudinal prospective cohort study of healthy children aged 5–14 years. Homeostasis model assessment (HOMA-IR), skinfolds (SSF), adiposity (percent fat, measured by dual-energy X-ray absorptiometry), serum leptin, and IGF-1 were measured annually in 235 children (134 boys). Pubertal onset was adduced from Tanner stage (TS) and from the age at which luteinizing hormone (LH) first became serially detectable (≥0.2 international units/L).

RESULTS
IR rose progressively from age 7 years, 3–4 years before TS2 was reached or LH became detectable. Rising adiposity and IGF-1 together explained 34% of the variance in IR in boys and 35% in girls (both P &lt; 0.001) over the 3 years preceding pubertal onset. The contribution of IGF-1 to IR was greater in boys, despite their comparatively lower IGF-1 levels.

CONCLUSIONS
IR starts to rise in mid-childhood, some years before puberty. Its emergence relates more to the age of the child than to pubertal onset. More than 60% of the variation in IR prior to puberty was unexplained. The demography of childhood diabetes is changing, and prepubertal IR may be important.