bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary genomics of the pandemic 2009 H1N1 influenza viruses (pH1N 1v)
Authors: Qu Yanhua , Zhang Ruiying , Cui Peng , Song Gang , Duan Ziyuan , Lei Fumin 
Published: May 2011

Abstract

Background
A new strain of human H1N1 influenza A viruses was broken out in the April 2009 and caused worldwide pandemic emergency. The present study is trying to estimate a temporal reassortment history of 2009 H1N1 viruses by phylogenetic analysis based on a total 394 sequences of H1N1viruses isolated from swine, human and avian.

Results
Phylogenetic trees of eight gene segments showed that viruses sampled from human formed a well-supported clade, whereas swine and avian lineages were intermixed together. A new divergence swine sublineage containing gene segments of 2009 H1N1 viruses was characterized, which were closely related with swine viruses collected from USA and South Korea during 2004 to 2007 in six segments (PB2, PB1, PA, HA, NP and NS), and to swine viruses isolated from Thailand during 2004 to 2005 in NA and M. Substitution rates were varied drastically among eight segments and the average substitution rate was generally higher in 2009 H1N1 than in swine and human viruses (F

2

,23 = 5.972, P < 0.01). Similarly, higher d
N/d
S substitution ratios were identified in 2009 H1N1 than in swine and human viruses except M2 gene (F
2, 25 = 3.779, P < 0.05). The ages of 2009 H1N1 viruses were estimated around 0.1 to 0.5 year, while their common ancestors with closest related swine viruses existed between 9.3 and 17.37 years ago.

Conclusion
Our results implied that at least four reassortments or transmissions probably occurred before 2009 H1N1 viruses. Initial reassortment arose in 1976 and avian-like Eurasian swine viruses emerged. The second transmission happened in Asia and North America between 1988 and 1992, and mostly influenced six segments (PB2, PB1, PA, HA, NP and NS). The third reassortment occurred between North American swine and avian viruses during 1998 to 2000, which involved PB2 and PA segments. Recent reassortments occurred among avian-to-swine reassortant, Eurasian and classical swine viruses during 2004 to 2005. South Korea, Thailand and USA, were identified as locations where reassortments most likely happened. The co-circulation of multiple swine sublineages and special lifestyle in Asia might have facilitated mixing of diverse influenza viruses, leading to generate a novel virus strain.
Palliative radiotherapy in patients with a symptomatic pelvic mass of metastatic colorectal cancer
Authors: Bae Sun Hyun , Park Won , Choi Doo Ho , Nam Heerim , Kang Won Ki , Park Young Suk , Park Joon Oh , Chun Ho Kyung , Lee Woo Yong , Yun Seong Hyeon , Kim Hee Cheol 
Published: May 2011

Abstract

Background
To evaluate the palliative role of radiotherapy (RT) and define the effectiveness of chemotherapy combined with palliative RT (CCRT) in patients with a symptomatic pelvic mass of metastatic colorectal cancer.

Methods
From August 1995 to December 2007, 80 patients with a symptomatic pelvic mass of metastatic colorectal cancer were treated with palliative RT at Samsung Medical Center. Initial presenting symptoms were pain (68 cases), bleeding (18 cases), and obstruction (nine cases). The pelvic mass originated from rectal cancer in 58 patients (73%) and from colon cancer in 22 patients (27%). Initially 72 patients (90%) were treated with surgery, including 64 complete local excisions; 77% in colon cancer and 81% in rectal cancer. The total RT dose ranged 8-60 Gy (median: 36 Gy) with 1.8-8 Gy per fraction. When the α/β for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the median RT dose was 46.8 Gy10 (14.4-78). Twenty one patients (26%) were treated with CCRT. Symptom palliation was assessed one month after the completion of RT.

Results
Symptom palliation was achieved in 80% of the cases. During the median follow-up period of five months (1-44 months), 45% of the cases experienced reappearance of symptoms; the median symptom control duration was five months. Median survival after RT was six months. On univariate analysis, the only significant prognostic factor for symptom control duration was BED ≥40 Gy10 (p < 0.05), and CCRT was a marginally significant factor (p = 0.0644). On multivariate analysis, BED and CCRT were significant prognostic factors for symptom control duration (p < 0.05).

Conclusions
RT was an effective palliation method in patients with a symptomatic pelvic mass of metastatic colorectal cancer. For improvement of symptom control rate and duration, a BED ≥ 40 Gy10 is recommended when possible. Considering the low morbidity and improved symptom palliation, CCRT might be considered in patients with good performance status.
Modularity-based credible prediction of disease genes and detection of disease subtypes on the phenotype-gene heterogeneous network
Authors: Yao Xin , Hao Han , Li Yanda , Li Shao 
Published: May 2011

Abstract

Background
Protein-protein interaction networks and phenotype similarity information have been synthesized together to discover novel disease-causing genes. Genetic or phenotypic similarities are manifested as certain modularity properties in a phenotype-gene heterogeneous network consisting of the phenotype-phenotype similarity network, protein-protein interaction network and gene-disease association network. However, the quantitative analysis of modularity in the heterogeneous network and its influence on disease-gene discovery are still unaddressed. Furthermore, the genetic correspondence of the disease subtypes can be identified by marking the genes and phenotypes in the phenotype-gene network. We present a novel network inference method to measure the network modularity, and in particular to suggest the subtypes of diseases based on the heterogeneous network.

Results
Based on a measure which is introduced to evaluate the closeness between two nodes in the phenotype-gene heterogeneous network, we developed a Hitting-Time-based method, CIPHER-HIT, for assessing the modularity of disease gene predictions and credibly prioritizing disease-causing genes, and then identifying the genetic modules corresponding to potential subtypes of the queried phenotype. The CIPHER-HIT is free to rely on any preset parameters. We found that when taking into account the modularity levels, the CIPHER-HIT method can significantly improve the performance of disease gene predictions, which demonstrates modularity is one of the key features for credible inference of disease genes on the phenotype-gene heterogeneous network. By applying the CIPHER-HIT to the subtype analysis of Breast cancer, we found that the prioritized genes can be divided into two sub-modules, one contains the members of the Fanconi anemia gene family, and the other contains a reported protein complex MRE11/RAD50/NBN.

Conclusions
The phenotype-gene heterogeneous network contains abundant information for not only disease genes discovery but also disease subtypes detection. The CIPHER-HIT method presented here is effective for network inference, particularly on credible prediction of disease genes and the subtype analysis of diseases, for example Breast cancer. This method provides a promising way to analyze heterogeneous biological networks, both globally and locally.
The Hannover experience: Surgical treatment of tongue cancer - A clinical retrospective evaluation over a 30 years period
Authors: Kokemueller Horst , Rana Majeed , Rublack Jennifer , Eckardt Andre , Tavassol Frank , Schumann Paul , Lindhorst Daniel , Ruecker Martin , Gellrich Nils-Claudius 
Published: May 2011

AbstractObjectivesIn this retrospective study, we present a clinical review of our experience with tongue cancer in order to obtain valid criteria for therapeutic decision-making.Materials and methodsBetween 1980 and 2009, a total of 341 patients with squamous cell carcinoma of the tongue were treated at our Department. The average follow-up was 5.2 years. 309 patients received surgical treatment, which was combined in nearly 10% with neoadjuvant and in nearly 20% with postoperative radio(chemo)therapy. 32 patients were excluded from surgery and received primary radiation.ResultsLocal and regional failure occurred in 23.9% and 20.4%, leading to a total failure rate of 37.2% after an average duration of 1,6 years. N-Status, extracapsular spread and clear margins were identified as the dominant factors for survival, which was calculated with 54.5% after 5 years.ConclusionsWe recommend categorical bilateral neck dissection in order to reliably remove occult lymph node metastases. Adjuvant treatment modalities should be applied more frequently in controlled clinical trials and should generally be implemented in cases with unclear margins and lymphatic spread.Clinical relevanceThis study provides new treatment strategies for primary tumour disease and for tumour recurrence.
Primary Tumor Response to Preoperative Chemoradiation With or Without Oxaliplatin in Locally Advanced Rectal Cancer: Pathologic Results of the STAR-01 Randomized Phase III Trial
Authors: Aschele Carlo , Cionini Luca , Lonardi Sara , Pinto Carmine , Cordio Stefano , Rosati Gerardo , Artale Salvatore , Tagliagambe Angiolo , Ambrosini Giovanni , Rosetti Paola , Bonetti Andrea , Negru Maria Emanuela , Tronconi Maria Chiara , Luppi Gabriele , Silvano Giovanni , Corsi Domenico Cristiano , Bochicchio Anna Maria , Chiaulon Germana , Gallo Maurizio , Boni Luca 
Published: May 2011

Purpose To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Patients and Methods Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m2/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m2 weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here. Results Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P < .001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P < .001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014). Conclusion Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.
Phosphodiesterases in endocrine physiology and disease
Authors: Vezzosi Delphine , Bertherat Jérôme 
Published: May 2011

The cAMP–protein kinase A pathway plays a central role in the development and physiology of endocrine tissues. cAMP mediates the intracellular effects of numerous peptide hormones. Various cellular and molecular alterations of the cAMP-signaling pathway have been observed in endocrine diseases.Phosphodiesterases (PDEs) are key regulatory enzymes of intracellular cAMP levels. Indeed, PDEs are the only known mechanism for inactivation of cAMP by catalysis to 5′-AMP. It has been suggested that disruption of PDEs could also have a role in the pathogenesis of many endocrine diseases. This review summarizes the most recent advances concerning the role of the PDEs in the physiopathology of endocrine diseases. The potential significance of this knowledge can be easily envisaged by the development of drugs targeting specific PDEs.
Cancer risk in hyperprolactinemia patients: a population-based cohort study
Authors: Berinder Katarina , Akre Olof , Granath Fredrik , Hulting Anna-Lena 
Published: May 2011

ObjectiveExperimental evidence indicates that prolactin might play a role in tumorigenesis of several human cancers, but data on cancer risk in hyperprolactinemia patients are sparse. The aim of this study was to investigate cancer risk in hyperprolactinemia patients.DesignA population-based matched cohort study in Sweden.MethodsThe hyperprolactinemia cohort consisted of patients hospitalized for hyperprolactinemia from 1987 to 1995 identified in the National Patient Register (n=585) and a hospital cohort of prolactinoma patients at Karolinska University Hospital (n=384). For each patient, ten matched individuals were identified via the Register of Population. Cancer occurrence was ascertained via the Swedish Cancer Registry. Hazard ratios (HRs) were estimated by Cox proportional hazards regression.ResultsSeventy-three malignant tumors were identified in the hyperprolactinemia patients and 660 tumors in the comparison group (HR 1.31; 95% confidence interval (CI): 1.02–1.68), mainly attributed to an increased risk of upper gastrointestinal cancer in both males and females (HR 3.69; 95% CI: 1.70–8.03) and hematopoietic cancer in females (HR 3.51; 95% CI: 1.06–11.6). Twelve breast cancers occurred in the female patients, corresponding to an HR of 1.09 (95% CI: 0.60–1.99). Prostate cancer risk in hyperprolactinemia men was reduced (HR 0.40; 95% CI: 0.16–0.99).ConclusionsAn increased overall cancer risk was found in hyperprolactinemia patients, but no increased risk of breast cancer in women and a reduced risk of prostate cancer in men. These findings warrant further investigations and to be confirmed in larger studies but may indicate the importance of an active treatment strategy and follow-up of hyperprolactinemia patients.
Sexual desire in female-to-male transsexual persons: exploration of the role of testosterone administration
Authors: Wierckx Katrien , Elaut Els , Van Caenegem Eva , Van De Peer Fleur , Dedecker David , Van Houdenhove Ellen , T'Sjoen Guy 
Published: May 2011

ObjectiveTo describe sexual desire in female-to-male transsexual persons post sex reassignment surgery (SRS). The associations between serum androgen levels and sexual desire are examined.DesignSingle center cross-sectional study.MethodsForty-five female-to-male transsexual persons post SRS completed a standardized questionnaire assessing sexual desire (Sexual Desire Inventory). In addition, participants were asked questions on sexual desire before starting hormone treatment and having SRS. Serum levels of testosterone, LH and sex hormone-binding globulin were measured on fasting morning serum samples.ResultsIn retrospect, 73.9% of the participants reported an increase in sexual desire after hormone treatment and SRS. Solitary sexual desire scores were significantly correlated with frequency of masturbation (r=0.835;P<0.001), whereas frequency of sexual intercourse with a partner was not. No direct associations were found between testosterone and solitary or dyadic sexual desire. However, ANOVA showed an independent effect of LH on solitary sexual desire (P<0.001).Post hocanalysis revealed that female-to-male transsexual persons with elevated levels of LH, indicating suboptimal testosterone therapy, reported significantly lower solitary sexual desire levels (than those with low LH levels;P=0.007). Suppressed LH levels were also associated with having a higher need for sexual activities (P=0.009) and a higher frequency of excessive sexual desire (P=0.007).ConclusionMost female-to-male transsexual persons report on a marked increase in sexual desire after testosterone treatment and SRS. No direct associations between levels of testosterone and solitary or dyadic sexual desire were found. However, measures of sexual desire were inversely associated with LH levels.
Leptin administration to overweight and obese subjects for 6 months increases free leptin concentrations but does not alter circulating hormones of the thyroid and IGF axes during weight loss induced by a mild hypocaloric diet
Authors: Shetty Greeshma K , Matarese Giuseppe , Magkos Faidon , Moon Hyun-Seuk , Liu Xiaowen , Brennan Aoife M , Mylvaganam Geetha , Sykoutri Despina , DePaoli Alex M , Mantzoros Christos S 
Published: May 2011

ObjectiveShort-term energy deprivation reduces leptin concentrations and alters the levels of circulating hormones of the hypothalamic–pituitary–peripheral axis in lean subjects. Whether the reduction in leptin concentration during long-term weight loss in obese individuals is linked to the same neuroendocrine changes seen in lean, leptin-sensitive subjects remains to be fully clarified.MethodsIn this study, 24 overweight and obese adults (16 women and eight men; body mass index (BMI): 27.5–38.0 kg/m2) were prescribed a hypocaloric diet (−500 kcal/day) and were randomized to receive recombinant methionyl leptin (n=18, metreleptin, 10 mg/day self-injected s.c.) or placebo (n=6, same volume and time as metreleptin) for 6 months.ResultsMetreleptin administration did not affect weight loss beyond that induced by hypocaloric diet alone (P for interaction=0.341) but increased the serum concentrations of total leptin by six- to eight-fold (P<0.001) and led to the generation of anti-leptin antibodies. Despite free leptin concentration (P for interaction=0.041) increasing from 9±1 ng/ml at baseline to 43±15 and 36±12 ng/ml at 3 and 6 months, respectively, changes in circulating hormones of the thyroid and IGF axes at 3 and 6 months were not significantly different in the placebo- and metreleptin-treated groups.ConclusionsLeptin does not likely mediate changes in neuroendocrine function in response to weight loss induced by a mild hypocaloric diet in overweight and obese subjects.
Adrenal vein sampling using rapid cortisol assays in primary aldosteronism is useful in centers with low success rates
Authors: Betz Matthias J , Degenhart Christoph , Fischer Evelyn , Pallauf Anna , Brand Volker , Linsenmaier Ulrich , Beuschlein Felix , Bidlingmaier Martin , Reincke Martin 
Published: May 2011

ObjectiveAdrenal vein sampling (AVS) is considered the gold standard in the differential diagnosis of primary aldosteronism (PA), but success rates vary between centers. We hypothesized that rapid (intraprocedure) cortisol measurement can improve performance in a center with initially low AVS success rate.DesignWe analyzed 46 patients with confirmed PA studied between 2008 and 2010. Forty-seven PA patients studied between 2004 and 2008 identified by retrospective chart review served as controls. All patients were treated at a single tertiary care university hospital.MethodsStarting in 2008, rapid cortisol assays (RCA) were performed in all patients during the AVS procedure. A cortisol gradient of ≥2.0 between adrenal vein and a femoral vein sample was used as success criterion. Up to two repeat samples were drawn if adrenal vein cortisol was below this threshold.ResultsDuring the control period 26 of 47 AVS were successful (55%). After introduction of RCA, 39 out of 46 AVS (85%) were successful (P=0.003). In 21 of the 46 cases (46%) a resampling was necessary. The increase in overall success was due to an increase in successful right AVS (85 vs 62% before introduction of RCA; P=0.02) and a training effect (P=0.024 for trend).ConclusionRCA during AVS are useful in centers with an initially low AVS success rate.
Long-term DHEA substitution in female adrenocortical failure, body composition, muscle function, and bone metabolism: a randomized trial
Authors: Christiansen Jens J , Bruun Jens M , Christiansen Jens S , Jørgensen Jens Otto , Gravholt Claus H 
Published: May 2011

ContextAdrenal derived androgens are low in women with adrenal failure. The physiological consequences of substitution therapy are uncertain.ObjectiveTo investigate the effects of DHEA substitution in women with adrenal failure on body composition, fuel metabolism, and inflammatory markers.Design, participants and interventionIn this study, ten female patients (median age 38.5 years, range 28–52) with adrenal failure were treated with DHEA 50 mg for 6 months in a double-blind, randomized, placebo-controlled, and crossover study. The participants underwent dual-energy X-ray absorptiometry (DXA) scan, computed tomography scan of abdominal fat, indirect calorimetry, bicycle ergometry, muscle and fat biopsies, and blood samples.ResultsBaseline androgens were normalized to fertile range during active treatment. Anthropometric data were unaffected, but lean body mass (LBM) slightly increased compared with placebo (delta LBM (kg) placebo versus DHEA: −0.48±6.1 vs 1.6±3.4,P=0.02) with no alterations in total or abdominal fat mass. PTH increased with DHEA, but no significant changes were observed in other bone markers or in bone mineral content. The mRNA levels of markers of tissue inflammation (adiponectin, interleukin 6 (IL6), IL10, monocyte chemoattractant protein 1, and tumor necrosis factor α) in fat and muscle tissue were unaffected by DHEA treatment, as was indirect calorimetry and maximal oxygen uptake. A high proportion of self-reported seborrheic side effects were recorded (60%).ConclusionIn female adrenal failure, normalization of androgens with DHEA 50 mg for 6 months had no effects on muscle, fat, and bone tissue and on fuel metabolism in this small study. A small increase in LBM was observed. Treatment was associated with a high frequency of side effects.
Quality Measures for the Care of Children With Otitis Media With Effusion
Authors: Lannon Carole , Peterson Laura E. , Goudie Anthony 
Published: May 2011

BACKGROUND:
Current national efforts provide an opportunity to integrate performance measures into clinical practice and improve outcomes for children.

OBJECTIVE:
The goal of this study was to explore issues in developing and testing measures of care for children with otitis media with effusion (OME).

METHODS:
We assessed compliance with diagnostic, evaluation, and treatment measures for OME adapted from preliminary work of the Physician Consortium for Performance Improvement, using chart data in a convenience sample of practices from 2 primary care networks (Cincinnati Pediatric Research Group and the American Academy of Pediatrics Quality Improvement Innovation Network). Children aged 2 months to 12 years with at least 1 visit with a specified OME code during a 1-year period were included.

RESULTS:
Of 23 practices, 4 could not locate eligible visits. Nineteen practices submitted 378 abstractions (range: 3–37 per practice) with 15 identifying &lt;30 eligible visits. Performance on diagnosis (33%) and hearing evaluation (29%) measures was low but high on measures of appropriate medication use (97% decongestant/antihistamine, 87% antibiotics, and 95% corticosteroids). Thirty-five percent of records documented antibiotic use concurrent with OME; only 16% of the 94 cases that cited reason for prescribing were appropriate. Using methods that consider appropriate clinical action, a more accurate rate for appropriate use of antibiotics was 68%.

CONCLUSIONS:
Coding, case finding, and evaluating appropriateness of treatment are some of the issues that will need to be considered to assess the care of children with OME. This study emphasizes the importance of testing proposed quality of care measures in “real-world” settings.