bluuebunny/crossref_metadata_2025_split huggingface dataset:
R-spondin1 and FOXL2act into two distinct cellular types during goat ovarian differentiation
Authors: Kocer Ayhan , Pinheiro Iris , Pannetier Maëlle , Renault Lauriane , Parma Pietro , Radi Orietta , Kim Kyung-Ah , Camerino Giovanna , Pailhoux Eric 
Published: April 2008

Abstract

Background
Up to now, two loci have been involved in XX sex-reversal in mammals following loss-of-function mutations, PIS (Polled Intersex Syndrome) in goats and R-spondin1 (RSPO1) in humans. Here, we analyze the possible interaction between these two factors during goat gonad development. Furthermore, since functional redundancy between different R-spondins may influence gonad development, we also studied the expression patterns of RSPO2, 3 and 4.

Results
Similarly to the mouse, RSPO1 shows a sex-dimorphic expression pattern during goat gonad development with higher levels in the ovaries. Interestingly, the PIS mutation does not seem to influence its level of expression. Moreover, using an RSPO1 specific antibody, the RSPO1 protein was localized in the cortical area of early differentiating ovaries (36 and 40 dpc). This cortical area contains the majority of germ cell that are surrounded by FOXL2 negative somatic cells. At latter stages (50 and 60 dpc) RSPO1 protein remains specifically localized on the germ cell membranes. Interestingly, a time-specific relocation of RSPO1 on the germ cell membrane was noticed, moving from a uniform distribution at 40 dpc to a punctuated staining before and during meiosis (50 and 60 dpc respectively). Interestingly, also RSPO2 and RSPO4 show a sex-dimorphic expression pattern with higher levels in the ovaries. Although RSPO4 was found to be faintly and belatedly expressed, the expression of RSPO2 increases at the crucial 36 dpc stage, as does that of FOXL2. Importantly, RSPO2 expression appears dramatically decreased in XX PIS-/- gonads at all three tested stages (36, 40 and 50 dpc).

Conclusion
During goat ovarian development, the pattern of expression of RSPO1 is in agreement with its possible anti-testis function but is not influenced by the PIS mutation. Moreover, our data suggest that RSPO1 may be associated with germ cell development and meiosis. Interestingly, another RSPO gene, RSPO2 shows a sex-dimorphic pattern of expression that is dramatically influenced by the PIS mutation.
Weak correlation between sequence conservation in promoter regions and in protein-coding regions of human-mouse orthologous gene pairs
Authors: Chiba Hirokazu , Yamashita Riu , Kinoshita Kengo , Nakai Kenta 
Published: April 2008

Abstract

Background
Interspecies sequence comparison is a powerful tool to extract functional or evolutionary information from the genomes of organisms. A number of studies have compared protein sequences or promoter sequences between mammals, which provided many insights into genomics. However, the correlation between protein conservation and promoter conservation remains controversial.

Results
We examined promoter conservation as well as protein conservation for 6,901 human and mouse orthologous genes, and observed a very weak correlation between them. We further investigated their relationship by decomposing it based on functional categories, and identified categories with significant tendencies. Remarkably, the 'ribosome' category showed significantly low promoter conservation, despite its high protein conservation, and the 'extracellular matrix' category showed significantly high promoter conservation, in spite of its low protein conservation.

Conclusion
Our results show the relation of gene function to protein conservation and promoter conservation, and revealed that there seem to be nonparallel components between protein and promoter sequence evolution.
Numbers needed to treat calculated from responder rates give a better indication of efficacy in osteoarthritis trials than mean pain scores
Authors: Moore R Andrew , Moore Owen A , Derry Sheena , McQuay Henry J 
Published: April 2008

Abstract
Introduction
Osteoarthritis trials usually report average changes in visual analogue scale (VAS) pain, and examine the difference between treatment and placebo. We investigated whether dichotomous responder analysis provides a more informative interpretation of drug efficacy.

Methods
Merck supplied the number of patients who, by 6 weeks, had achieved pain relief compared with a baseline of 0% or more, 10% or more, 20% or more, and so on at equal intervals up to 90% or more. These different levels of pain relief were used to distinguish different definitions of responders, for example at least 50% pain relief from baseline. Numbers and percentages of patients achieving each level were identified. Information was sought from a dose–response trial over 6 weeks in osteoarthritis using placebo and using etoricoxib at 5, 10, 30 and 60 mg daily.

Results
With placebo, the proportions of patients achieving at least 20%, 50% and 70% pain relief over baseline at 6 weeks were 30%, 11% and 2%. With 60 mg etoricoxib the equivalent percentages were 74%, 49% and 29%. The numbers needed to treat for 30 mg and 60 mg etoricoxib to produce at least 50% pain relief at 6 weeks compared with placebo were 4.2 (95% confidence interval 3.8 to 8.6) and 2.6 (2.0 to 3.9), respectively. Levels of pain relief of 50% and above discriminated best between different doses of etoricoxib.

Conclusion
Responder analysis seemed to be more sensitive than examination of average changes in VAS pain scores. Validation would require calculations to be performed on a set of trials using individual patient data not available in publications.
Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models
Authors: Wolkewitz Martin , Vonberg Ralf Peter , Grundmann Hajo , Beyersmann Jan , Gastmeier Petra , Bärwolff Sina , Geffers Christine , Behnke Michael , Rüden Henning , Schumacher Martin 
Published: April 2008

Abstract
Introduction
Pneumonia is a very common nosocomial infection in intensive care units (ICUs). Many studies have investigated risk factors for the development of infection and its consequences. However, the evaluation in most of theses studies disregards the fact that there are additional competing events, such as discharge or death.

Methods
A prospective cohort study was conducted over 18 months in five intensive care units at one university hospital. All patients that were admitted for at least 2 days were included, and surveillance of nosocomial pneumonia was conducted. Various potential risk factors (baseline- and time-dependent) were evaluated in two competing risks models: the acquisition of nosocomial pneumonia and discharge (dead or alive; model 1) and for the risk of death in the ICU and discharge alive (model 2).

Results
Patients from 1,876 admissions were included. A total of 158 patients developed nosocomial pneumonia. The main risk factors for nosocomial pneumonia in the multivariate analysis in model 1 were: elective surgery (cause-specific hazard ratio = 1.95; 95% CI 1.33 to 2.85) or emergency surgery (1.59; 95% CI 1.10 to 2.28) prior to ICU admission, usage of a nasogastric tube (3.04; 95% CI 1.25 to 7.37) and mechanical ventilation (5.90; 95% CI 2.47 to 14.09). Nosocomial pneumonia prolonged the length of ICU stay but was not directly associated with a fatal outcome (p = 0.55).

Conclusion
More studies using competing risk models, which provide more accurate data compared to naive survival curves or logistic models, should be carried out to verify the impact of risk factors and patient characteristics for the acquisition of nosocomial infections and infection-associated mortality.
Growth Hormone Decreases Visceral Fat and Improves Cardiovascular Risk Markers in Women with Hypopituitarism: A Randomized, Placebo-Controlled Study
Authors: Beauregard Catherine , Utz Andrea L. , Schaub Amber E. , Nachtigall Lisa , Biller Beverly M. K. , Miller Karen K. , Klibanski Anne 
Published: April 2008

Abstract
Context: Data regarding gender-specific efficacy of GH on critical endpoints are lacking. There are no randomized, placebo-controlled studies of physiological GH therapy solely in women.
Objective: Our objective was to determine the effects of physiological GH replacement on cardiovascular risk markers and body composition in women with GH deficiency (GHD).
Design: This was a 6-month, randomized, placebo-controlled, double-blind study.
Setting: The study was conducted at the General Clinical Research Center.
Study Participants: 43 women with GHD due to hypopituitarism were included in the study.
Intervention: Study participants were randomized to receive GH (goal mid-normal serum IGF-1) or placebo.
Main Outcome Measures: Cardiovascular risk markers, including high-sensitivity C-reactive protein, tissue plasminogen activator, and body composition, including visceral adipose tissue by cross-sectional computed tomography, were measured.
Results: Mean daily GH dose was 0.67 mg. The mean IGF-1 sd score increased from −2.5 ± 0.3 to −1.4 ± 0.9 (GH) (P &lt; 0.0001 vs. placebo). High-sensitivity C-reactive protein decreased by 38.2 ± 9.6% (GH) vs.18.2 ± 6.0% (placebo) (P = 0.03). Tissue plasminogen activator and total cholesterol decreased, and high-density lipoprotein increased. Homeostasis model assessment-insulin resistance and other markers were unchanged. Body fat decreased [−5.1 ± 2.0 (GH) vs. 1.9 ± 1.0% (placebo); P = 0.002] as did visceral adipose tissue [−9.0 ± 5.9 (GH) vs. 4.3 ± 2.7% (placebo); P = 0.03]. Change in IGF-1 level was inversely associated with percent change in visceral adipose tissue (r = −0.61; P = 0.002), total body fat (r = −0.69; P &lt; 0.0001), and high-sensitivity C-reactive protein (r = −0.51; P = 0.003).
Conclusions: Low-dose GH replacement in women with GHD decreased total and visceral adipose tissue and improved cardiovascular markers, with a relatively modest increase in IGF-1 levels and without worsening insulin resistance.
Inhibition of CYP21A2 Enzyme Activity Caused by Novel Missense Mutations Identified in Brazilian and Scandinavian Patients
Authors: Soardi F. C. , Barbaro M. , Lau I. F. , Lemos-Marini S. H. V. , Baptista M. T. M. , Guerra-Junior G. , Wedell A. , Lajic S. , de Mello M. P. 
Published: April 2008

Abstract
Background: Most patients with 21-hydroxylase deficiency carry CYP21A1P-derived mutations, but an increasing number of novel and rare mutations have been reported in disease-causing alleles.
Objective: Functional effects of three novel (p.G56R, p.L107R, p.L142P) and one recurrent (p.R408C) CYP21A2 mutations were investigated. The degree of enzyme impairment caused by p.H62L alone or combined to p.P453S was also analyzed.
Design: The study included 10 Brazilian and two Scandinavian patients. To determine the deleterious role of each mutant protein, in vitro assays were performed in transiently transfected COS-1 cells. For a correct genotype-phenotype correlation, the enzymatic activities were evaluated toward the two natural substrates, 17-hydroxyprogesterone and progesterone.
Results: Low levels of residual activities obtained for p.G56R, p.L107R, p.L142P, and p.R408C mutants classified them as classical congenital adrenal hyperplasia mutations, whereas the p.H62L showed an activity within the range of nonclassical mutations. Apparent kinetic constants for p.H62L confirmed the nonclassical classification as the substrate binding capacity was within the same magnitude for mutant and normal enzymes. A synergistic effect was observed for the allele bearing the p.H62L+p.P453S combination because it caused a significant reduction in the enzymatic activity.
Conclusions: We describe the functional analysis of five rare missense mutations identified in Brazilian and Scandinavian patients. The p.G56R, p.L107R, and p.L142P are reported for the first time. Most probably these novel mutations are closer to null than the p.I172N, but for the p.G56R, that might not be the case, and the p.H62L is definitely a nonclassical mutation.
Daptomycin-Induced Acute Renal and Hepatic Toxicity Without Rhabdomyolysis
Authors: Abraham George , Finkelberg Dmitry , Spooner Linda M 
Published: April 2008

Objective: To report a case of a patient who experienced acute renal and hepatic toxicity following administration of daptomycin and review previously published case reports of renal and hepatic dysfunction with daptomycin. Case Summary: A 35-year-old man receiving daptomycin 4 mg/kg (275 mg) intravenously once daily (started 5 wk prior to presentation for presumed osteomyelitis) presented to the emergency department with elevations in serum creatinine and hepatic transaminase levels. He did not experience creatine kinase (CK) elevation or rhabdomyolysis. Following discontinuation of daptomycin, his renal and hepatic function improved. Discussion: To our knowledge, this is the first case of daptomycin-induced hepatotoxicity with acute renal failure in the absence of rhabdomyolysis and CK abnormalities. Previously published case reports described patients with a variety of elevations in liver function tests, serum creatinine, and CK with daptomycin. In our patient, the acute renal and hepatic toxicity was probable according to the Naranjo probability scale. Conclusions: Although daptomycin is a well-tolerated antibacterial agent, clinicians should consider periodic monitoring of liver function and renal function tests to identify potential adverse effects.
Very Late Stent Thrombosis After Dual Antiplatelet Therapy Discontinuation in a Patient with a History of Acute Stent Thrombosis
Authors: Bhatt Snehal H , Hauser Thomas H 
Published: April 2008

Objective: To describe a case of very late stent thrombosis after dual antiplatelet discontinuation in a patient with a previous history of stent thrombosis. Case Summary: A 62-year-old man with a history of coronary artery disease, multiple acute coronary syndromes requiring percutaneous coronary interventions with multiple stent placements, and acute stent thrombosis resulting in ST segment elevation myocardial infarction presented to the hospital with chest pain. The chest pain was not relieved by 4 sublingual nitroglycerin tablets. Five days prior to his presentation, the patient had been instructed to discontinue both aspirin and clopidogrel in preparation for a left ankle fusion procedure. He was taken to the cardiac catheterization laboratory where he was found to have thrombosis in a sirolimus-eluting stent placed more than 3 years ago. Thrombectomy and balloon angioplasty were performed, and the patient completed his hospital course without complications. Discussion: Stent thrombosis associated with drug-eluting stents is a complicated pathophysiologic phenomenon with multiple patient-, procedure-, and device-related factors. Application of these risk factors to quantify the risk of stent thrombosis as they apply to a single patient is unknown. Discontinuation of recommended dual antiplatelet therapy with aspirin plus a thienopyridine has been identified as a major risk factor for stent thrombosis, but the optimal duration of dual antiplatelet therapy remains unknown. Current recommendations suggest extending dual antiplatelet therapy beyond one year in patients with low bleeding risk. Conclusions: Given the overall data at this time and the severity of stent thrombosis, it seems prudent to continue dual antiplatelet therapy with aspirin indefinitely plus a thienopyridine for at least one year, with continuation beyond one year on a case-by-case basis depending on the risks of in-stent thrombosis and bleeding. In patients with a low risk of bleeding, indefinite continuation of dual antiplatelet therapy may be reasonable.
Appropriate Use of Dopamine Agonists and Levodopa in Restless Legs Syndrome in an Ambulatory Care Setting
Authors: Molokwu Ogochukwu Chidozie 
Published: April 2008

Background: Dopaminergic agents are the mainstay therapy for the management of restless tegs syndrome (RLS). There are no clear guidelines on RLS management, and no study has evaluated the appropriate use of dopaminergic agents in RLS. Objective: To evaluate the appropriateness of use of dopaminergic agents in RLS management in an ambulatory care setting based on the most current scientific evidence. Methods: A retrospective drug utilization evaluation was conducted in patients who received levodopa or dopamine agonist for RLS from July 1, 2006, to July 31, 2007. Patients’ medical records were reviewed and data were collected on demographics; comorbidities; laboratory values; doses of levodopa or dopamine agonists; prescribing physician's specialty; and use of alcohol, tobacco, and caffeine. RESULTS: A total of 27 patients were included in the study for data collection and analysis. Twenty-two (81%) patients were on levodopa and 5 (19%) were on ropinirole. RLS severity was documented in only 2 (7%) patients. Serum ferritin levels and transferrin-iron saturation (Tsat) percentages were not obtained in 18 (67%) and 20 (74%) of the patients, respectively. Two (7%) patients had ferritin levels less than 50 ng/mL, and 7 (26%) patients had ferritin levels greater than 50 ng/mL. Fourteen (52%) patients were taking concurrent antidepressants and 6 (22%) were taking sedating antihistamines. Alcohol and tobacco use was documented in 2 (7%) and 8 (30%) patients, respectively. Twenty-six (96%) of the prescribing physicians were primary care providers. Conclusions: The findings of this study confirm the need for provider education about the appropriate use of levodopa and dopamine agonists in patients with RLS. Appropriate use of these drugs may help decrease unnecessary adverse effects, complications, and costs.
Acapulco in Dreams and Reality
Authors: Niblo Stephen R. , Niblo Diane M. 
Published: April 2008

This article is an exploration of the development of Acapulco, primarily in the twentieth century. It looks at the political economy of the resort and its importance to the Mexican model of development. It also examines the myths, tourist promotion, and the place of Acapulco in popular culture.
Este artículo es una exploración del desarrollo de Acapulco, principalmente en el siglo veinte. Se estudia la economía política de ese centro turístico y su importancia para el modelo mexicano de desarrollo. Examina también los mitos, la promoción turística, y el lugar de Acapulco en la cultura popular.
Efficient Control of Population Structure in Model Organism Association Mapping
Authors: Kang Hyun Min , Zaitlen Noah A , Wade Claire M , Kirby Andrew , Heckerman David , Daly Mark J , Eskin Eleazar 
Published: April 2008

AbstractGenomewide association mapping in model organisms such as inbred mouse strains is a promising approach for the identification of risk factors related to human diseases. However, genetic association studies in inbred model organisms are confronted by the problem of complex population structure among strains. This induces inflated false positive rates, which cannot be corrected using standard approaches applied in human association studies such as genomic control or structured association. Recent studies demonstrated that mixed models successfully correct for the genetic relatedness in association mapping in maize and Arabidopsis panel data sets. However, the currently available mixed-model methods suffer from computational inefficiency. In this article, we propose a new method, efficient mixed-model association (EMMA), which corrects for population structure and genetic relatedness in model organism association mapping. Our method takes advantage of the specific nature of the optimization problem in applying mixed models for association mapping, which allows us to substantially increase the computational speed and reliability of the results. We applied EMMA to in silico whole-genome association mapping of inbred mouse strains involving hundreds of thousands of SNPs, in addition to Arabidopsis and maize data sets. We also performed extensive simulation studies to estimate the statistical power of EMMA under various SNP effects, varying degrees of population structure, and differing numbers of multiple measurements per strain. Despite the limited power of inbred mouse association mapping due to the limited number of available inbred strains, we are able to identify significantly associated SNPs, which fall into known QTL or genes identified through previous studies while avoiding an inflation of false positives. An R package implementation and webserver of our EMMA method are publicly available.
Uptake, elimination, and biotransformation of aqueous and dietary DDT in marine fish
Authors: Kwong Raymond W. M , Yu Peter K. N , Lam Paul K. S , Wang Wen-Xiong 
Published: April 2008

Abstract
To understand the biokinetics and potential risks of p,p-dichlorodiphenyltrichloroethane (DDT) and its metabolites, p,p'-dichlorodiphenyldichloroethylene (DDE) and p,p'-dichlorodiphenyldichloroethane (DDD), in fish, we exposed the black sea breams (Acanthopagrus schlegeli) to aqueous and dietary DDTs and then evaluated the bioaccumulation, distribution, biotransformation, and elimination of DDTs under controlled laboratory conditions. The fish rapidly accumulated DDTs from both routes of exposure, particularly the gills and viscera. Elimination of DDTs following aqueous or dietary uptake was slow, and biotranslocation of DDTs was significant during the exposure period but negligible during the depuration period. The biotransformation process was more significant following dietary exposure. During depuration, DDE was the major biotransformed product in the sea breams' carcasses while DDD was the major product in the gills and viscera. However, DDD had a significantly higher elimination rate than DDE and, subsequently, the fish retained more DDE in the body. Intraspecies variability in the elimination and biotransformation processes in fish was observed. We demonstrated that the route of exposure significantly affected the fate and biokinetics of DDTs in fish. The application of a dynamic model provided a tool for quantifying the elimination and biotransformation of DDT in fish. The present study provided insights into the bioaccumulation and biotransformation pathways of DDT in fish that could have important ecotoxicological implications.
The Young Men’s Survey Phase II: Hepatitis B Immunization and Infection Among Young Men Who Have Sex With Men
Authors: Weinbaum Cindy M. , Lyerla Rob , MacKellar Duncan A. , Valleroy Linda A. , Secura Gina M. , Behel Stephanie K. , Bingham Trista , Celentano David D. , Koblin Beryl A. , LaLota Marlene , Shehan Douglas A. , Thiede Hanne , Torian Lucia V. 
Published: April 2008

Objectives. We measured the prevalence of hepatitis B virus (HBV) immunization and HBV infection among men aged 23 to 29 years who have sex with men. Methods. We analyzed data from 2834 men who have sex with men in 6 US metropolitan areas. Participants were interviewed and tested for serologic markers of immunization and HBV infection in 1998 through 2000. Results. Immunization prevalence was 17.2%; coverage was 21.0% among participants with private physicians or health maintenance organizations and 12.6% among those with no source of health care. Overall, 20.6% had markers of HBV infection, ranging from 13.7% among the youngest to 31.0% among the oldest participants. Among those susceptible to HBV, 93.5% had regular sources of health care, had been tested for HIV, or had been treated for a sexually transmitted disease. Conclusions. Although many young men who have sex with men have access to health care, most are not immunized against HBV. To reduce morbidity from HBV in this population, providers of health care, including sexually transmitted disease and HIV prevention services, should provide vaccinations or referrals for vaccination.