bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary primacy of sodium bioenergetics
Authors: Mulkidjanian Armen Y , Galperin Michael Y , Makarova Kira S , Wolf Yuri I , Koonin Eugene V 
Published: April 2008

AbstractBackgroundThe F- and V-type ATPases are rotary molecular machines that couple translocation of protons or sodium ions across the membrane to the synthesis or hydrolysis of ATP. Both the F-type (found in most bacteria and eukaryotic mitochondria and chloroplasts) and V-type (found in archaea, some bacteria, and eukaryotic vacuoles) ATPases can translocate either protons or sodium ions. The prevalent proton-dependent ATPases are generally viewed as the primary form of the enzyme whereas the sodium-translocating ATPases of some prokaryotes are usually construed as an exotic adaptation to survival in extreme environments.ResultsWe combine structural and phylogenetic analyses to clarify the evolutionary relation between the proton- and sodium-translocating ATPases. A comparison of the structures of the membrane-embedded oligomeric proteolipid rings of sodium-dependent F- and V-ATPases reveals nearly identical sets of amino acids involved in sodium binding. We show that the sodium-dependent ATPases are scattered among proton-dependent ATPases in both the F- and the V-branches of the phylogenetic tree.ConclusionBarring convergent emergence of the same set of ligands in several lineages, these findings indicate that the use of sodium gradient for ATP synthesis is the ancestral modality of membrane bioenergetics. Thus, a primitive, sodium-impermeable but proton-permeable cell membrane that harboured a set of sodium-transporting enzymes appears to have been the evolutionary predecessor of the more structurally demanding proton-tight membranes. The use of proton as the coupling ion appears to be a later innovation that emerged on several independent occasions.ReviewersThis article was reviewed by J. Peter Gogarten, Martijn A. Huynen, and Igor B. Zhulin. For the full reviews, please go to the Reviewers' comments section.
A scoring matrix approach to detecting miRNA target sites
Authors: Moxon Simon , Moulton Vincent , Kim Jan T 
Published: April 2008

Abstract

Background
Experimental identification of microRNA (miRNA) targets is a difficult and time consuming process. As a consequence several computational prediction methods have been devised in order to predict targets for follow up experimental validation. Current computational target prediction methods use only the miRNA sequence as input. With an increasing number of experimentally validated targets becoming available, utilising this additional information in the search for further targets may help to improve the specificity of computational methods for target site prediction.

Results
We introduce a generic target prediction method, the Stacking Binding Matrix (SBM) that uses both information about the miRNA as well as experimentally validated target sequences in the search for candidate target sequences. We demonstrate the utility of our method by applying it to both animal and plant data sets and compare it with miRanda, a commonly used target prediction method.

Conclusion
We show that SBM can be applied to target prediction in both plants and animals and performs well in terms of sensitivity and specificity. Open source code implementing the SBM method, together with documentation and examples are freely available for download from the address in the Availability and Requirements section.
Gluten-free vegan diet induces decreased LDL and oxidized LDL levels and raised atheroprotective natural antibodies against phosphorylcholine in patients with rheumatoid arthritis: a randomized study
Authors: Elkan Ann-Charlotte , Sjöberg Beatrice , Kolsrud Björn , Ringertz Bo , Hafström Ingiäld , Frostegård Johan 
Published: April 2008

Abstract
Introduction
The purpose of this study was to investigate the effects of vegan diet in patients with rheumatoid arthritis (RA) on blood lipids oxidized low-density lipoprotein (oxLDL) and natural atheroprotective antibodies against phosphorylcholine (anti-PCs).

Methods
Sixty-six patients with active RA were randomly assigned to either a vegan diet free of gluten (38 patients) or a well-balanced non-vegan diet (28 patients) for 1 year. Thirty patients in the vegan group completed more than 3 months on the diet regimen. Blood lipids were analyzed by routine methods, and oxLDL and anti-PCs were analyzed by enzyme-linked immunosorbent assay. Data and serum samples were obtained at baseline and after 3 and 12 months.

Results
Mean ages were 50.0 years for the vegan group and 50.8 years for controls. Gluten-free vegan diet induced lower body mass index (BMI) and low-density lipoprotein (LDL) and higher anti-PC IgM than control diet (p < 0.005). In the vegan group, BMI, LDL, and cholesterol decreased after both 3 and 12 months (p < 0.01) and oxLDL after 3 months (p = 0.021) and trendwise after 12 months (p = 0.090). Triglycerides and high-density lipoprotein did not change. IgA anti-PC levels increased after 3 months (p = 0.027) and IgM anti-PC levels increased trendwise after 12 months (p = 0.057). There was no difference in IgG anti-PC levels. In the control diet group, IgM anti-PC levels decreased both after 3 and 12 months (p < 0.01). When separating vegan patients into clinical responders and non-responders at 12 months, the effects on oxLDL and anti-PC IgA were seen only in responders (p < 0.05).

Conclusion
A gluten-free vegan diet in RA induces changes that are potentially atheroprotective and anti-inflammatory, including decreased LDL and oxLDL levels and raised anti-PC IgM and IgA levels.
Exogenous tumour necrosis factor α induces suppression of autoimmune arthritis
Authors: Kim Eugene Y , Chi Howard H , Rajaiah Rajesh , Moudgil Kamal D 
Published: April 2008

Abstract
Introduction
Our previous studies showed that arthritic Lewis (LEW) rats produced the highest levels of tumour necrosis factor (TNF)α in the recovery phase of adjuvant arthritis (AA), suggesting a correlation between high TNFα levels and reduced severity of arthritis. To further explore this correlation, we compared the TNFα secretion profile of the AA-resistant Wistar Kyoto (WKY) rats with that of LEW rats, determined the effect of exogenous TNFα on the course of AA in LEW rats, and examined various mechanisms involved in TNFα-induced disease modulation.

Methods
A cohort each of LEW and WKY rats was immunised subcutaneously with heat-killed Mycobacterium tuberculosis H37Ra (Mtb). At different time points thereafter, subgroups of rats were killed and their draining lymph node cells were tested for cytokine production. Another group of LEW rats was injected with TNFα intraperitoneally daily for a total of 10 injections, 3 before and 6 after Mtb challenge, and then observed for signs of AA. In parallel, TNFα-treated rats were examined for changes in other cytokines, in CD4+CD25+ T cell frequency, and in indoleamine 2,3-dioxygenase (IDO) mRNA expression levels.

Results
LEW rats displayed a TNFα secretion profile that was opposite to that of the WKY rats. Furthermore, TNFα treatment significantly downmodulated the severity of AA in LEW rats, and decreased the interferon (IFN)-γ secretion in response to the pathogenic determinant of the disease-related antigen. No significant alterations were observed in other parameters tested.

Conclusion
The role of endogenous TNFα in the induction and propagation of arthritis is well established. However, exogenous TNFα can downmodulate the course of AA, displaying an immunoregulatory functional attribute of this cytokine.
Clinical response after two cycles compared to HER2, Ki-67, p53, and bcl-2 in independently predicting a pathological complete response after preoperative chemotherapy in patients with operable carcinoma of the breast
Authors: von Minckwitz Gunter , Sinn Hans-Peter , Raab Günter , Loibl Sibylle , Blohmer Jens-Uwe , Eidtmann Holger , Hilfrich Jörn , Merkle Elisabeth , Jackisch Christian , Costa Serban D , Caputo Angelika , Kaufmann Manfred ,   the German Breast Group (GBG)
Published: April 2008

Abstract
Introduction
To investigate the predictive value of clinical and biological markers for a pathological complete remission after a preoperative dose-dense regimen of doxorubicin and docetaxel, with or without tamoxifen, in primary operable breast cancer.

Methods
Patients with a histologically confirmed diagnosis of previously untreated, operable, and measurable primary breast cancer (tumour (T), nodes (N) and metastases (M) score: T2-3(≥ 3 cm) N0-2 M0) were treated in a prospectively randomised trial with four cycles of dose-dense (bi-weekly) doxorubicin and docetaxel (ddAT) chemotherapy, with or without tamoxifen, prior to surgery. Clinical and pathological parameters (menopausal status, clinical tumour size and nodal status, grade, and clinical response after two cycles) and a panel of biomarkers (oestrogen and progesterone receptors, Ki-67, human epidermal growth factor receptor 2 (HER2), p53, bcl-2, all detected by immunohistochemistry) were correlated with the detection of a pathological complete response (pCR).

Results
A pCR was observed in 9.7% in 248 patients randomised in the study and in 8.6% in the subset of 196 patients with available tumour tissue. Clinically negative axillary lymph nodes, poor tumour differentiation, negative oestrogen receptor status, negative progesterone receptor status, and loss of bcl-2 were significantly predictive for a pCR in a univariate logistic regression model, whereas in a multivariate analysis only the clinical nodal status and hormonal receptor status provided significantly independent information. Backward stepwise logistic regression revealed a response after two cycles, with hormone receptor status and lymph-node status as significant predictors. Patients with a low percentage of cells stained positive for Ki-67 showed a better response when treated with tamoxifen, whereas patients with a high percentage of Ki-67 positive cells did not have an additional benefit when treated with tamoxifen. Tumours overexpressing HER2 showed a similar response to that in HER2-negative patients when treated without tamoxifen, but when HER2-positive tumours were treated with tamoxifen, no pCR was observed.

Conclusion
Reliable prediction of a pathological complete response after preoperative chemotherapy is not possible with clinical and biological factors routinely determined before start of treatment. The response after two cycles of chemotherapy is a strong but dependent predictor. The only independent factor in this subset of patients was bcl-2.

Trial registration number
NCT00543829
Reduced reliance on the trace element selenium during evolution of mammals
Authors: Lobanov Alexey V , Hatfield Dolph L , Gladyshev Vadim N 
Published: April 2008

Abstract
Background
Selenium (Se) is an essential trace element that occurs in proteins in the form of selenocysteine (Sec). It is transported throughout the body in the form of Sec residues in Selenoprotein P (SelP), a plasma protein of unclear origin recently proposed as an experimental marker of dietary Se status.

Results
Here, we report that the amino-terminal domain of SelP is distantly related to ancestral bacterial thiol oxidoreductases of the thioredoxin superfamily, and that its carboxy-terminal Se transport domain may have originated in early metazoan evolution by de novo accumulation of Sec residues. Reconstruction of evolutionary changes in the Se transport domain indicates a decrease in Sec content of SelP specifically in the mammalian lineage via replacement of Sec with cysteine (Cys). Sec content of mammalian SelPs varies more than two-fold and is lowest in rodents and primates. Compared to mammals, fish show higher Sec content of SelP, larger selenoproteomes, elevated SelP gene expression, and higher levels of tissue Se. In addition, mammals replaced Sec with Cys in several proteins and lost several selenoproteins altogether, whereas such events are not found in fish.

Conclusion
These data suggest that evolution from fish to mammals was accompanied by decreased use of Sec and that analyses of SelP, selenoproteomes and Sec/Cys transitions provide a genetic marker of utilization of this trace element in vertebrates. The evolved reduced reliance on Se raises questions regarding the need to maximize selenoprotein expression by Se dietary supplements in situations when pathology is not imminent, a currently accepted practice.
Prediction Model for Estimating the Survival Benefit of Adjuvant Radiotherapy for Gallbladder Cancer
Authors: Wang Samuel J. , Fuller C. David , Kim Jong-Sung , Sittig Dean F. , Thomas Charles R. , Ravdin Peter M. 
Published: April 2008

Purpose The benefit of adjuvant radiotherapy (RT) for gallbladder cancer remains controversial because most published data are from small, single-institution studies. The purpose of this study was to construct a survival prediction model to enable individualized predictions of the net survival benefit of adjuvant RT for gallbladder cancer patients based on specific tumor and patient characteristics. Methods A multivariate Cox proportional hazards model was constructed using data from 4,180 patients with resected gallbladder cancer diagnosed from 1988 to 2003 from the Surveillance, Epidemiology, and End Results database. Patient and tumor characteristics were included as covariates and assessed for association with overall survival (OS) with and without adjuvant RT. The model was internally validated for discrimination and calibration using bootstrap resampling. Results On multivariate regression analysis, the model showed that age, sex, papillary histology, stage, and adjuvant RT were significant predictors of OS. The survival prediction model demonstrated good calibration and discrimination, with a bootstrap-corrected concordance index of 0.71. The model predicts that adjuvant RT provides a survival benefit in node-positive or ≥ T2 disease. A nomogram and a browser-based software tool were built from the model that can calculate individualized estimates of predicted net survival gain attributable to adjuvant RT, given specific input parameters. Conclusion In the absence of large, prospective, randomized, clinical trial data, a regression model can be used to make individualized predictions of the expected survival improvement from the addition of adjuvant RT after gallbladder cancer resection.
Individual Physician Practice Variation in Hematopoietic Cell Transplantation
Authors: Lee Stephanie J. , Joffe Steven , Artz Andrew S. , Champlin Richard E. , Davies Stella M. , Jagasia Madan , Kernan Nancy A. , Loberiza Fausto R. , Soiffer Robert J. , Eapen Mary 
Published: April 2008

Purpose Previous studies have evaluated practice variation in hematopoietic cell transplantation (HCT) among transplant centers and countries. There are no studies investigating individual physician practice variation in HCT. Methods An international Internet-based survey of transplant physicians collected data on medical decisions made by adult and pediatric HCT physicians. Multivariable analyses identified practitioner and transplant center characteristics predictive of medical decision making. Results Analysis of 526 assessable respondents showed a wide variation in management approaches to specific clinical scenarios. Pediatric and adult transplant physicians differed significantly in their management strategies for chronic myeloid leukemia, acute and chronic graft-versus-host disease, and choice of graft source for patients with aplastic anemia. Among adult transplant physicians, there was little agreement on the patient factors favoring reduced intensity conditioning or myeloablative conditioning. Conclusion These results emphasize the heterogeneity of worldwide transplant practices. Local preferences or biases likely result in similar patients being offered different transplant and treatment procedures. The degree of practice variation also highlights the need for clinical trials to clarify areas of controversy. Where clinical trials are not feasible, data from observational studies may be the best available evidence to guide practice.
Epidemiologic Features of the Presentation of Critical Congenital Heart Disease: Implications for Screening
Authors: Schultz Amy H. , Localio A. Russell , Clark Bernard J. , Ravishankar Chitra , Videon Nancy , Kimmel Stephen E. 
Published: April 2008

OBJECTIVE. Critical congenital heart disease has been proposed as a target of newborn screening. This study aimed to define the incidence and timing of significant physiologic compromise attributable to critical congenital heart disease as well as the distribution of vulnerable lesions. These descriptive parameters must be defined to evaluate the impact and feasibility of any proposed screening strategy.METHODS. A retrospective cohort study of neonates who had critical congenital heart disease and were admitted to a single institution was conducted. Critical congenital heart disease was defined as congenital heart disease that required invasive intervention or resulted in death in the first 30 days of life. Significant physiologic compromise was defined by severe metabolic acidosis, seizure, cardiac arrest, or laboratory evidence of renal or hepatic injury before invasive intervention. Significant physiologic compromise was classified as potentially preventable when it occurred as a result of undiagnosed congenital heart disease after 12 hours of life.RESULTS. Significant physiologic compromise occurred in 76 (15.5%) of 490 patients, and potentially preventable significant physiologic compromise occurred in 33 (6.7%) of 490 patients. Most (83%) significant physiologic compromise as a result of unrecognized congenital heart disease occurred after 12 hours of age. A total of 90.9% of cases of potentially preventable significant physiologic compromise had aortic arch obstruction. The incidence of potentially preventable significant physiologic compromise as a result of congenital heart disease in the general population is estimated to be 1 per 15000 to 1 per 26000 live births.CONCLUSIONS. The incidence and timing of significant physiologic compromise as a result of critical congenital heart disease seems amenable to postnatal screening. Any viable screening strategy must be sensitive for lesions with aortic arch obstruction.
Prevalence and Risk Factors of Elevated Pulmonary Artery Pressures in Children With Sickle Cell Disease
Authors: Pashankar Farzana D. , Carbonella Judith , Bazzy-Asaad Alia , Friedman Alan 
Published: April 2008

OBJECTIVES. The objectives of this study were (1) to determine the prevalence and risk factors of elevated pulmonary artery pressures in children with homozygous SS or Sβ° thalassemia using Doppler echocardiography and (2) to determine a correlation between abnormal transcranial Doppler examinations and elevated pulmonary artery pressures.
METHODS. Screening echocardiograms were prospectively performed during an annual comprehensive clinic visit on children who were older than 6 years and had homozygous SS or Sβ° thalassemia. Detailed history, examination, and laboratory tests were done, and transcranial Doppler examinations were obtained in children 2 to 14 years of age. Pulmonary hypertension was defined as pulmonary artery systolic pressure of at least 30 mmHg corresponding to a peak tricuspid regurgitant jet velocity of ≥2.5 m/second. Mild pulmonary hypertension was defined as tricuspid regurgitant jet velocity ≥2.5 to 2.9 m/second. Moderate pulmonary hypertension was defined as tricuspid regurgitant jet velocity ≥3 m/second. Patients with pulmonary stenosis or right outflow obstruction were excluded. Characteristics were compared between patients with mild, moderate, and no pulmonary hypertension using 1-way analysis of variance for continuous variable and Fisher's exact test for categorical variables.
RESULTS. Of the 75 patients who had homozygous SS/Sβ° thalassemia and were older than 6 years, echocardiograms were obtained for 62 (82.6%). Thirty percent (19 of 62) of patients had elevated tricuspid regurgitant jet velocity ≥2.5 m/second. One third of these patients had tricuspid regurgitant jet velocity ≥3 m/second. All patients with elevated tricuspid regurgitant jet velocity had SS disease. A high reticulocyte count, low oxygen saturation, and a high platelet count were significantly associated with elevated pulmonary artery pressures. There was no difference in age, gender, history of acute chest syndrome, hydroxyurea therapy, chronic blood transfusion, stroke, hemoglobin, and bilirubin between patients with and without elevated pulmonary artery pressures. A total of 47% patients with elevated tricuspid regurgitant jet velocity and 57% without elevated tricuspid regurgitant jet velocity had screening transcranial Doppler examinations. Transcranial Doppler examinations were normal for all patients.
CONCLUSIONS. High pulmonary artery pressures do occur in children with sickle cell disease. Screening by echocardiography can lead to early detection and intervention that may potentially reverse this disease process. There was no correlation between elevated pulmonary artery pressures and abnormal transcranial Doppler examination in our study.
Gymnastics-related Injuries to Children Treated in Emergency Departments in the United States, 1990–2005
Authors: Singh Shubha , Smith Gary A. , Fields Sarah K. , McKenzie Lara B. 
Published: April 2008

OBJECTIVE. The objective of this study was to describe the epidemiology of gymnastics-related injuries among children in the United States.METHODS. A retrospective analysis was conducted of data for children 6 through 17 years of age from the National Electronic Injury Surveillance System of the US Consumer Product Safety Commission for 1990 through 2005. Sample weights provided by the National Electronic Injury Surveillance System were used to calculate national estimates of gymnastics-related injuries. Injury rates were calculated for the most frequently occurring types of injury using gymnastics participation data.RESULTS. An estimated 425900 children 6 through 17 years of age were treated in US hospital emergency departments for gymnastics-related injuries during the 16-year period of 1990–2005. The number of injuries averaged 26600 annually. The number of injuries sustained per 1000 gymnastics participants per year for the pediatric population was 4.8. The number of injuries sustained per 1000 participants per year was greater for the ages 12 to 17 years (7.4) than for the ages 6 to 11 years (3.6). The place where an injury occurred include school (40.0%), a place of recreation or sports (39.7%), home (14.5%), or on other public property (5.8%). The body parts injured were upper extremity (42.3%), lower extremity (33.8%), head/neck (12.9%), trunk (10.4%), and other (0.6%). Injury diagnoses were strain/sprain (44.5%), fracture/dislocation (30.4%), abrasion/contusion (15.6%), laceration/avulsion (3.7%), concussion/closed head injury (1.7%), and other (4.2%). The majority (97.1%) of patients with gymnastics-related injuries were treated and released from the emergency department.CONCLUSIONS. Gymnastics has one of the highest injury rates of all girls' sports. Establishment of a national database for gymnastics-related injuries, including exposure data for direct calculation of injury rates, would permit better identification and monitoring of risk factors for gymnastics-related injuries and aid in the development, implementation, and evaluation of injury prevention strategies based on epidemiologic evidence.