bluuebunny/crossref_metadata_2025_split huggingface dataset:
The gender imbalance in academic medicine: a study of female authorship in the United Kingdom
Authors: Sidhu Reena , Rajashekhar Praveen , Lavin Victoria L , Parry Joanne , Attwood James , Holdcroft Anita , Sanders David S 
Published: August 2009

Summary Objectives A shortfall exists of female doctors in senior academic posts in the United Kingdom. Career progression depends on measures of esteem, including publication in prestigious journals. This study investigates gender differences in first and senior authorship in six peer-reviewed British journals and factors that are associated with publication rates. Design and main outcome measures Data was collected on United Kingdom first and senior authors who had published in the British Medical Journal, Lancet, British Journal of Surgery, Gut, British Journal of Obstetrics and Gynaecology and the Archives of Diseases in Childhood. Authorship and gender were quantified for 1970, 1980, 1990, 2000 and 2004 ( n=6457). In addition, selected questions from the Athena Survey of Science Engineering and Technology (ASSET2006), web-based doctor's self-report of publications were also analysed ( n=1162). Results Female first authors increased from 10.5% in 1970 to 36.5% in 2004 (p<0.001) while female senior authors only increased from 12.3% to 16.5% (p=0.046). Within individual journals, the largest rise was in British Journal of Obstetric and Gynaecology with 4.5- and 3-fold increases for first and senior authors, respectively. In contrast, female senior authors marginally declined in Gut and Lancet by 2.8% and 2.2%, respectively. ASSET2006 identified that female respondents who were parents were less likely to have publications as sole (p=0.02) and joint authors (p<0.001) compared to male respondents. Female respondents with care responsibilities for parents/partner also had less publications as lead authors compared to those without carer responsibilities (p<0.001). Conclusion The increase in UK female first authors is encouraging. In contrast, there is considerable lag and in some specialties a decline in female senior authors. Factors that could narrow the gender gap in authorship should be sought and addressed.
Interactive Modeling for Ongoing Utility of Pharmacogenetic Diagnostic Testing: Application for Warfarin Therapy
Authors: Linder Mark W , Bon Homme Marjorie , Reynolds Kristen K , Gage Brian F , Eby Charles , Silvestrov Natalia , Valdes Roland 
Published: August 2009

Abstract
Background: The application of pharmacogenetic results requires demonstrable correlations between a test result and an indicated specific course of action. We developed a computational decision-support tool that combines patient-specific genotype and phenotype information to provide strategic dosage guidance. This tool, through estimating quantitative and temporal parameters associated with the metabolism- and concentration-dependent response to warfarin, provides the necessary patient-specific context for interpreting international normalized ratio (INR) measurements.
Methods: We analyzed clinical information, plasma S-warfarin concentration, and CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genotypes for 137 patients with stable INRs. Plasma S-warfarin concentrations were evaluated by VKORC1 genotype (−1639G&gt;A). The steady-state plasma S-warfarin concentration was calculated with CYP2C9 genotype–based clearance rates and compared with actual measurements.
Results: The plasma S-warfarin concentration required to yield the target INR response is significantly (P &lt; 0.05) associated with VKORC1 −1639G&gt;A genotype (GG, 0.68 mg/L; AG, 0.48 mg/L; AA, 0.27 mg/L). Modeling of the plasma S-warfarin concentration according to CYP2C9 genotype predicted 58% of the variation in measured S-warfarin concentration: Measured [S-warfarin] = 0.67(Estimated [S-warfarin]) + 0.16 mg/L.
Conclusions: The target interval of plasma S-warfarin concentration required to yield a therapeutic INR can be predicted from the VKORC1 genotype (pharmacodynamics), and the progressive changes in S-warfarin concentration after repeated daily dosing can be predicted from the CYP2C9 genotype (pharmacokinetics). Combining the application of multivariate equations for estimating the maintenance dose with genotype-guided pharmacokinetics/pharmacodynamics modeling provides a powerful tool for maximizing the value of CYP2C9 and VKORC1 test results for ongoing application to patient care.
Second Liquid – an Intermediate Phase of Sublimation
Authors: Mosienko B. A. 
Published: August 2009

Abstract
According to current concepts there is only one mechanism of intermolecular interaction (Van der Waals forces). The question arises: Why does liquid exist? The search for answer to this question leads to the assumption that there are two mutually independent mechanisms of intermolecular interaction. This assumption, taken as an initial postulate, provides the possibility of existence of some other modification of liquid which is totally different from ordinary liquid by its physical properties. It has been proposed that it is precisely this modification (second liquid) that is the intermediate state of matter in the sublimation process. The arguments in favor of this hypothesis are adduced. Specifically, the existence of two modifications of liquid helium might be considered a serious empirical argument; in the view of proposed approach, superfluid helium II is the second liquid of helium in the bulk phase.
Effect of combination therapy with thyroxine (T4) and 3,5,3′-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study
Authors: Nygaard Birte , Jensen Ebbe Winther , Kvetny Jan , Jarløv Anne , Faber Jens 
Published: August 2009

BackgroundTreatment of hypothyroidism with 3,5,3′-triiodothyronine (T3) is controversial. A recent meta-analysis concludes that no evidence is present in favour of using T3. However, the analysis included a mixture of different patient groups and dose-regimens.ObjectiveTo compare the effect of combination therapy with thyroxine (T4) and T3 versus T4 monotherapy in patients with hypothyroidism on stable T4 substitution.Study designDouble-blind, randomised cross-over. Fifty micrograms of the usual T4 dose was replaced with either 20 μg T3 or 50 μg T4 for 12 weeks, followed by cross-over for another 12 weeks. The T4 dose was regulated if needed, intending unaltered serum TSH levels.EvaluationTests for quality of life (QOL) and depression (SF-36, Beck Depression Inventory, and SCL-90-R) at baseline and after both treatment periods.Inclusion criteriaSerum TSH between 0.1 and 5.0 mU/l on unaltered T4 substitution for 6 months.ResultsA total of 59 patients (55 women); median age 46 years. When comparing scores of QOL and depression on T4 monotherapy versus T4/T3 combination therapy, significant differences were seen in 7 out of 11 scores, indicating a positive effect related to the combination therapy. Forty-nine percent preferred the combination and 15% monotherapy (P=0.002). Serum TSH remained unaltered between the groups as intended.ConclusionIn a study design, where morning TSH levels were unaltered between groups combination therapy, (treated with T3 20 μg once daily) was superior to monotherapy by evaluating several QOL, depression and anxiety rating scales as well as patients own preference.
Elastosonographic evaluation of thyroid nodules in acromegaly
Authors: Scacchi Massimo , Andrioli Massimiliano , Carzaniga Chiara , Vitale Giovanni , Moro Mirella , Poggi Luca , Pecori Giraldi Francesca , Fatti Letizia M , Cavagnini Francesco 
Published: August 2009

ObjectiveUltrasound-elastography (US-E) appears to be a helpful tool for the diagnosis of thyroid cancer. In acromegaly, the prevalence of thyroid cancer is still debated. The aims of this study were to evaluate thyroid nodules in acromegaly and to establish the accuracy of US-E in providing information on their nature, using cytological analysis as a reference.Subjects and methodsUS-E was applied to 90 nodules detected in 25 acromegalic patients and to 94 nodules found in 31 non-acromegalic goitrous subjects. The lesions were classified according to the elasticity scores (ES) as soft (ES 1–2) or hard (ES 3–4). Fine needle aspiration cytology could be performed in 60.8% of hard nodules in acromegalics and in 86.7% of hard nodules in controls.ResultsThe prevalence of hard nodules was significantly higher in the whole group of acromegalic patients than in controls (56.8 vs 16.0%, P<0.0001). The prevalence of hard nodules in patients with active acromegaly (68.9%) was greater, though not to a statistically significant extent, than that observed in cured (44.4%) and controlled (52.5%) patients. Cytology revealed malignancy or suspect malignancy in four of the nodules of non-acromegalic subjects and in none of the nodules of acromegalic patients.ConclusionsThis study has demonstrated a high prevalence of stiff thyroid nodules in acromegaly, greater than that found in non-acromegalic goitrous subjects. In acromegalics, hard nodules appeared not to be malignant on cytopathological examination and are probably of fibrous nature. Thus, US-E appears to be of limited value for the diagnosis of thyroid cancer in acromegaly.
Vascular Endothelial Growth Factor Inhibition by dRK6 Causes Endothelial Apoptosis, Fibrosis, and Inflammation in the Heart via the Akt/eNOS Axis indb/dbMice
Authors: Whee Park Cheol , Wook Kim Hyung , Hee Lim Ji , Dong Yoo Ki , Chung Sungjin , Joon Shin Seok , Wha Chung Hyun , Ju Lee Sang , Chae Chi-Bom , Kim Yong-Soo , Sik Chang Yoon 
Published: August 2009

OBJECTIVEVascular endothelial growth factor (VEGF), which is associated with the stimulation of angiogenesis and collateral vessel synthase, is one of the crucial factors involved in cardiac remodeling in type 2 diabetes.RESEARCH DESIGN AND METHODSWe investigated VEGF inhibition by dRK6 on the heart in an animal model of type 2 diabetes. Male db/db and db/m mice either were treated with dRK6 starting at 7 weeks of age for 12 weeks (db/db-dRK6 and db/m-dRK6) or were untreated.RESULTSCardiac dysfunction and hypertrophy were noted by echocardiogram and molecular markers in the db/db-dRK6 mice. The presence of diabetes significantly suppressed the expression of VEGF receptor (VEGFR)-1 and VEGFR-2, phospho-Akt, and phospho-endothelial nitric oxide synthase (eNOS) in the heart. In db/db-dRK6 mice, dRK6 completely inhibited VEGFR-2, phospho-Akt, and phospho-eNOS expression, whereas no effect on VEGFR-1 was observed. Cardiac fibrosis, microvascular scarcity associated with an increase in apoptotic endothelial cells, and inflammation were prominent, as well as increase in antiangiogenic growth factors. Cardiac 8-hydroxy-deoxyguanine and hypoxia-inducible factor-1α expression were significantly increased. No such changes were found in the other groups, including the db/m-dRK6 mice. The number of apoptotic human umbilical vein endothelial cells was increased by dRK6 in a dose-dependent manner only at high glucose concentrations, and this was associated with a decrease in phospho-Akt and phospho-eNOS related to oxidative stress.CONCLUSIONSOur results demonstrated that systemic blockade of VEGF by dRK6 had deleterious effects on the heart in an animal model of type 2 diabetes; dRK6 induced downregulation of the VEGFR-2 and Akt-eNOS axis and enhancement of oxidative stress.
Adipose Tissue Exosome-Like Vesicles Mediate Activation of Macrophage-Induced Insulin Resistance
Authors: Deng Zhong-bin , Poliakov Anton , Hardy Robert W. , Clements Ronald , Liu Cunren , Liu Yuelong , Wang Jianhua , Xiang Xiaoyu , Zhang Shuangqin , Zhuang Xiaoying , Shah Spandan V. , Sun Dongmei , Michalek Sue , Grizzle William E. , Garvey Timothy , Mobley Jim , Zhang Huang-Ge 
Published: August 2009

OBJECTIVEWe sought to determine whether exosome-like vesicles (ELVs) released from adipose tissue play a role in activation of macrophages and subsequent development of insulin resistance in a mouse model.RESEARCH DESIGN AND METHODSELVs released from adipose tissue were purified by sucrose gradient centrifugation and labeled with green fluorescent dye and then intravenously injected into B6 ob/ob mice (obese model) or B6 mice fed a high-fat diet. The effects of injected ELVs on the activation of macrophages were determined through analysis of activation markers by fluorescence-activated cell sorter and induction of inflammatory cytokines using an ELISA. Glucose tolerance and insulin tolerance were also evaluated. Similarly, B6 mice with different gene knockouts including TLR2, TLR4, MyD88, and Toll-interleukin-1 receptor (TIR) domain–containing adaptor protein inducing interferon-β (TRIF) were also used for testing their responses to the injected ELVs.RESULTSELVs are taken up by peripheral blood monocytes, which then differentiate into activated macrophages with increased secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Injection of obELVs into wild-type C57BL/6 mice results in the development of insulin resistance. When the obELVs were intravenously injected into TLR4 knockout B6 mice, the levels of glucose intolerance and insulin resistance were much lower. RBP4 is enriched in the obELVs. Bone marrow–derived macrophages preincubated with recombinant RBP4 led to attenuation of obELV-mediated induction of IL-6 and TNF-α.CONCLUSIONSELVs released by adipose tissue can act as a mode of communication between adipose tissues and macrophages. The obELV-mediated induction of TNF-α and IL-6 in macrophages and insulin resistance requires the TLR4/TRIF pathway.
Validity and Reproducibility of Measurement of Islet Autoreactivity by T-Cell Assays in Subjects With Early Type 1 Diabetes
Authors: Herold Kevan C. , Brooks-Worrell Barbara , Palmer Jerry , Dosch H. Michael , Peakman Mark , Gottlieb Peter , Reijonen Helena , Arif Sefina , Spain Lisa M. , Thompson Clinton , Lachin John M. ,   the Type 1 Diabetes TrialNet Research Group
Published: August 2009

OBJECTIVEType 1 diabetes results from an immunemediated destruction of β-cells, likely to be mediated by T lymphocytes, but the sensitivity, specificity, and other measures of validity of existing assays for islet autoreactive T-cells are not well established. Such assays are vital for monitoring responses to interventions that may modulate disease progression.RESEARCH DESIGN AND METHODSWe studied the ability of cellular assays to discriminate responses in patients with type 1 diabetes and normal control subjects in a randomized blinded study in the U.S. and U.K. We evaluated the reproducibility of these measurements overall and to individual analytes from repeat collections.RESULTSResponses in the cellular immunoblot, U.K.-ELISPOT, and T-cell proliferation assays could differentiate patients from control subjects with odds ratios of 21.7, 3.44, and 3.36, respectively, with sensitivity and specificity as high as 74 and 88%. The class II tetramer and U.S. ELISPOT assays performed less well. Despite the significant association of the responses with type 1 diabetes, the reproducibility of the measured responses, both overall and individual analytes, was relatively low. Positive samples from normal control subjects (i.e., false positives) were generally isolated to single assays.CONCLUSIONSThe cellular immunoblot, U.K.-ELISPOT, and T-cell proliferation assays can distinguish responses from patients with type 1 diabetes and healthy control subjects. The limited reproducibility of the measurements overall and of responses to individual analytes may reflect the difficulty in detection of low frequency of antigen-specific T-cells or variability in their appearance in peripheral blood.
Obstetric and Perinatal Outcomes in Type 1 Diabetic Pregnancies
Authors: Persson Martina , Norman Mikael , Hanson Ulf 
Published: August 2009

OBJECTIVE
To perform comparative analyses of obstetric and perinatal outcomes between type 1 diabetic pregnancies and the general obstetric population in Sweden between 1991 and 2003.

RESEARCH DESIGN AND METHODS
This was a population-based study. Data were obtained from the Medical Birth Registry, covering &gt;98% of all pregnancies in Sweden. A total of 5,089 type 1 diabetic pregnancies and 1,260,207 control pregnancies were included. Odds ratios (ORs) were adjusted for group differences in maternal age, parity, BMI, chronic hypertensive disease, smoking habits, and ethnicity.

RESULTS
In type 1 diabetes, preeclampsia was significantly more frequent (OR 4.47 [3.77–5.31]) as was delivery by cesarean section (5.31 [4.97–5.69]) compared with results for the general population. Stillbirth (3.34 [2.46–4.55]), perinatal mortality (3.29 [2.50–4.33]), and major malformations (2.50 [2.13–2.94]) were more common in type 1 diabetic than in control pregnancies. The risk of very preterm birth (&lt;32 gestational weeks) was also higher among type 1 diabetic women (3.08 [2.45–3.87]). The incidence of fetal macrosomia (birth weight ≥2 SD above the mean) was increased in the diabetic group (11.45 [10.61–12.36]).

CONCLUSIONS
Type 1 diabetes in pregnancy is still associated with considerably increased rates of adverse obstetric and perinatal outcomes. The eightfold increased risk for fetal macrosomia in type 1 diabetic pregnancies is unexpected and warrants further investigation.
Insulin Sensitivity as an Independent Predictor of Fat Mass Gain in Hispanic Adolescents
Authors: Adam Tanja C. , Toledo-Corral Claudia , Lane Christianne J. , Weigensberg Marc J. , Spruijt-Metz Donna , Davies Jaimie N. , Goran Michael I. 
Published: August 2009

OBJECTIVE
The purpose of this study was to examine the relationship between changes in insulin sensitivity and subsequent changes in fat mass in obese Hispanic children over 3 consecutive years.

RESEARCH DESIGN AND METHODS
In a longitudinal research design, insulin sensitivity (Si) of 96 research participants was determined at baseline and 1 year later. Body adiposity was assessed at four assessments.

RESULTS
The change in Si during the first year of the study was a significant predictor of further fat mass development (P &lt; 0.05). Considering different directions of Si change, Si was a strong predictor for further fat mass development only in the group that decreased their Si (P &lt; 0.05).

CONCLUSIONS
The results show that the direction of change in insulin sensitivity at an early age is an important independent predictor for further fat mass development and emphasize the importance of insulin sensitivity as a primary target for long-term obesity prevention, as well as the significance of early age intervention.
Comparison of a DNA based PCR method with conventional methods for the detection of M. tuberculosis in Jos, Nigeria
Authors: Ani Agatha , Okpe Silvanis , Akambi Maxwell , Ejelionu Emeka , Yakubu Bitrus , Owolodun Olajide , Ekeh Peter , Oche Agbaji , Tyen Dinchi , Idoko John 
Published: August 2009

Background: To achieve early diagnosis and effective treatment of pulmonary tuberculosis, simple and sensitive methods that enhance the detection of Mycobacterium tuberculosis (M. tuberculosis) from clinical specimens are needed. This study compared the effectiveness and suitability of an insertion sequence (IS 6110) based polymerase chain reaction (PCR) assay with conventional methods for the detection of M. tuberculosis from clinical specimens in a resource-limited setting.
Methods: Sputa from 101 HIV-positive patients and 40 clinical specimens (sputa, gastic wash out, ascitic fluid, pleural fluid and cerebrospinal fluid) collected from children (HIV status unknown), all suspected for pulmonary tuberculosis at the Jos University Teaching Hospital, Jos, (JUTH) Nigeria, were examined by Ziehl Neelsen (ZN) smear microscopy, Lowenstein Jensen’s (LJ) egg-based culture, and PCR methods for the detection of M. tuberculosis.
Results: Mycobacteria was detected in 45/101 (44.6%) of the specimens from the HIV-positive patients and comprised of 6% ZN+culture+PCR+, 4% ZN-culture+PCR-, 16% ZN-culture+PCR+ and 19% ZN-culture-PCR+. Twenty-two of forty (55%) children were positive with 0% smear microscopy; 4/40 (10%) culture+PCR+; and 18/40 (45%) culture-PCR+. The sensitivity and specificity of the PCR for the HIV-positive patients were 85% and 74% respectively against 23% and 100% for ZN smear microscopy.
Conclusion: The IS6110 PCR is a rapid and sensitive method that is specific for the M. tuberculosis complex group. It is simple in our experience and increased the detection of M. tuberculosis from the specimens examined. We suggest its use for the detection of M. tuberculosis in high TB and HIV burden areas.
Ornithorhynchus anatinus (Platypus) Links the Evolution of Immunoglobulin Genes in Eutherian Mammals and Nonmammalian Tetrapods
Authors: Zhao Yaofeng , Cui Huiting , Whittington Camilla M. , Wei Zhiguo , Zhang Xiaofeng , Zhang Ziding , Yu Li , Ren Liming , Hu Xiaoxiang , Zhang Yaping , Hellman Lars , Belov Katherine , Li Ning , Hammarström Lennart 
Published: August 2009

Abstract
The evolutionary origins of mammalian immunoglobulin H chain isotypes (IgM, IgD, IgG, IgE, and IgA) are still incompletely understood as these isotypes differ considerably in structure and number from their counterparts in nonmammalian tetrapods. We report in this study that the platypus (Ornithorhynchus anatinus) Ig H chain constant region gene locus contains eight Ig encoding genes, which are arranged in an μ-δ-ο-γ2-γ1-α1-ε-α2 order, spanning a total of ∼200 kb DNA, encoding six distinct isotypes. The ο (ο for Ornithorhynchus) gene encodes a novel Ig H chain isotype that consists of four constant region domains and a hinge, and is structurally different from any of the five known mammalian Ig classes. This gene is phylogenetically related to υ (ε) and γ, and thus appears to be a structural intermediate between these two genes. The platypus δ gene encodes ten heavy chain constant region domains, lacks a hinge region and is similar to IgD in amphibians and fish, but strikingly different from that in eutherian mammals. The platypus Ig H chain isotype repertoire thus shows a unique combination of genes that share similarity both to those of nonmammalian tetrapods and eutherian animals and demonstrates how phylogenetically informative species can be used to reconstruct the evolutionary history of functionally important genes.