bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Analysis of Methylation of Genomic Loci in Early-Stage Rectal Cancer Predicts Distant Recurrence
Authors: de Maat Michiel F.G. , van de Velde Cornelis J.H. , van der Werff Martijn P.J. , Putter Hein , Umetani Naoyuki , Klein-Kranenbarg Elma Meershoek , Turner Roderick R. , van Krieken J. Han J.M. , Bilchik Anton , Tollenaar Rob A.E.M. , Hoon Dave S.B. 
Published: May 2008

Purpose There are no accurate prognostic biomarkers specific for rectal cancer. Epigenetic aberrations, in the form of DNA methylation, accumulate early during rectal tumor formation. In a preliminary study, we investigated absolute quantitative methylation changes associated with tumor progression of rectal tissue at multiple genomic methylated-in-tumor (MINT) loci sequences. We then explored in a different clinical patient group whether these epigenetic changes could be correlated with clinical outcome. Patients and Methods Absolute quantitative assessment of methylated alleles was used to assay methylation changes at MINT 1, 2, 3, 12, 17, 25, and 31 in sets of normal, adenomatous, and malignant tissues from 46 patients with rectal cancer. Methylation levels of these biomarkers were then assessed in operative specimens of 251 patients who underwent total mesorectal excision (TME) without neoadjuvant radiotherapy in a multicenter clinical trial. Results Methylation at MINT 2, 3, and 31 increased 11-fold (P = .005), 15-fold (P < .001), and two-fold (P = .02), respectively, during adenomatous transformation in normal rectal epithelium. Unsupervised grouping analyses of quantitative MINT methylation data of TME trial patients demonstrated two prognostic subclasses. In multivariate analysis of node-negative patients, this subclassification was the only predictor for distant recurrence (hazard ratio [HR], 4.17; 95% CI, 1.72 to 10.10; P = .002), cancer-specific survival (HR, 3.74; 95% CI, 1.4 to 9.43; P = .003), and overall survival (HR, 2.68; 95% CI, 1.41 to 5.11; P = .005). Conclusion Methylation levels of specific MINT loci can be used as prognostic variables in patients with American Joint Committee on Cancer stage I and II rectal cancer. Quantitative epigenetic classification of rectal cancer merits evaluation as a stratification factor for adjuvant treatment in early disease.
Lapatinib Versus Hormone Therapy in Patients With Advanced Renal Cell Carcinoma: A Randomized Phase III Clinical Trial
Authors: Ravaud Alain , Hawkins Robert , Gardner Jason P. , von der Maase Hans , Zantl Niko , Harper Peter , Rolland Frédéric , Audhuy Bruno , Machiels Jean-Pascal , Pétavy Frank , Gore Martin , Schöffski Patrick , El-Hariry Iman 
Published: May 2008

Purpose Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2–positive breast cancer. In the current phase III open-label trial, lapatinib was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2. Patients and Methods Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy—stratified by Karnofsky performance status and number of metastatic sites—were randomly assigned to lapatinib 1,250 mg daily or HT. The primary end point was time to progression (TTP); secondary end points included overall survival (OS), safety, and biomarker analyses. Results Four hundred sixteen patients were enrolled onto the study. Median TTP was 15.3 weeks for lapatinib versus 15.4 weeks for HT (hazard ratio [HR] = 0.94; P = .60), and median OS was 46.9 weeks for lapatinib versus 43.1 weeks for HT (HR = 0.88; P = .29). In a biomarker analysis of patients with EGFR-overexpressed tumors (3+ by immunohistochemistry [IHC]; n = 241) median TTP was 15.1 weeks for lapatinib versus 10.9 weeks for HT (HR = 0.76; P = .06), and median OS was 46.0 weeks for lapatinib versus 37.9 weeks for HT (HR = 0.69; P = .02). These results were confirmed by Cox regression analysis. No unexpected toxicities were observed; the most commonly reported drug-related adverse events (all grades) for lapatinib were rash (44%) and diarrhea (40%). Conclusion Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines, and the study supports that lapatinib prolonged OS relative to HT in patients with 3+ EGFR status determined by IHC.
Use of Antidepressants and Risk of Cancer in Individuals Infected With HIV
Authors: Stebbing Justin , Powles Tom , Mandalia Sundhiya , Nelson Mark , Gazzard Brian , Bower Mark 
Published: May 2008

Purpose Preclinical and cohort studies suggest that certain antidepressants are associated with a predisposition to cancer whereas others decrease the risk. We aimed to assess whether different classes of antidepressants were associated with changes in cancer incidence in a population of HIV-1 infected individuals, based on duration of exposure. Methods Antidepressant exposure was measured from date of first prescription of the antidepressant until the date of last follow-up or cancer diagnosis. Univariate and multivariate analyses were performed to establish the risk of AIDS-related cancers and non–AIDS-related cancers according to whether patients were receiving selective serotonin reuptake inhibitors, tricyclic antidepressants, or other medicines for depression. We analyzed data for time exposed to antidepressants, before and during the era of highly active antiretroviral therapy (HAART). Results From a cohort of 10,997 patients representing 52,656 years of follow-up attending a large HIV center during the pre-HAART and HAART eras, a total of 2,004 (18%) were prescribed antidepressants representing 15,850 years exposed. A total of 1,607 (15%) individuals were diagnosed with cancer. There were no significant associations between any class of antidepressant and any type of cancer (P = .19), in either the pre-HAART or HAART era (P = .23), and use of serotonin reuptake inhibitors did not alter the risk of Burkitt lymphoma. Conclusion Antidepressants, irrespective of their class, do not affect cancer risk in HIV-infected individuals.
The effect of endovenous laser ablation on restless legs syndrome
Authors: Hayes C A , Kingsley J R , Hamby K R , Carlow J 
Published: May 2008

Objectives Venous disease was proposed as a cause of restless legs syndrome (RLS) by Dr Karl A Ekbom in 1944, but has since remained largely unexplored. This study examines the effect of endovenous laser ablation (ELA) in patients with concurrent RLS and duplex-proven superficial venous insufficiency (SVI). Methods Thirty-five patients with moderate to very severe RLS (as defined by the 2003 National Institute of Health (NIH) RLS criteria) and duplex-proven SVI completed an international RLS rating scale questionnaire (IRLS) and underwent standard duplex examination to objectively measure the baseline severity of their conditions. They were separated into non-operative and operative cohorts. The operative cohort underwent ELA of refluxing superficial axial veins using the CoolTouch CTEV 1320 nm laser and ultrasound-guided sclerotherapy of the associated varicose veins with foamed sodium tetradecyl sulphate (STS). All patients then completed a follow-up IRLS questionnaire. Baseline and follow-up IRLS scores were compared. Results Operative correction of the SVI decreased the mean IRLS score by 21.4 points from 26.9 to 5.5, corresponding to an average of 80% improvement in symptoms. A total of 89% of patients enjoyed a decrease in their score of ≥15 points. Fifty-three percent of patients had a follow-up score of ≤5, indicating their symptoms had been largely alleviated and 31% had a follow-up score of zero, indicating a complete relief of RLS symptoms. Conclusions ELA of refluxing axial veins with the CTEV 1320 nm laser and foamed STS sclerotherapy of associated varicosities alleviates RLS symptoms in patients with SVI and moderate to very severe RLS. Recommendations SVI should be ruled-out in all patients with RLS before initiation or continuation of drug therapy.
Corrosion of Phosphoric Irons in Acidic Environments
Authors: Sahoo Gadadhar , Balasubramaniam R. 
Published: May 2008

Abstract
The corrosion behavior of phosphoric irons (i.e., Fe-P alloys containing low phosphorus in the range 0.1 to 0.5 wt. %), prepared by ingot metallurgy route, was evaluated in acidic and chloride environments, e.g., 0.25 M H2SO4 of pH 0.6, 0.5 M Na2SO4 of pH 3 and 3.5 % NaCl of pH 6.8. A plain carbon steel and a low alloy (Cu-Cr) steel were also studied for comparison purpose. The effect of Cu and Cr additions was beneficial in a highly acidic condition. While similar corrosion rates observed for plain carbon steel and low alloy steel in 0.5 M Na2SO4 of pH 3, a slightly higher corrosion rate was observed for phosphoric irons. All alloys exhibited lowest and similar corrosion rates in neutral 3.5 % NaCl corrosive media. The linearity of Tafel slopes in the cathodic region varied with the pH of the solution. Corrosion rates were higher at lower pH due to the major contribution of hydrogen evolution reaction to the cathodic current.
Antipituitary antibodies after traumatic brain injury: is head trauma-induced pituitary dysfunction associated with autoimmunity?
Authors: Tanriverdi Fatih , De Bellis Annamaria , Bizzarro Antonio , Sinisi Antonio Agostino , Bellastella Giuseppe , Pane Elena , Bellastella Antonio , Unluhizarci Kursad , Selcuklu Ahmet , Casanueva Felipe F , Kelestimur Fahrettin 
Published: May 2008

ObjectiveTraumatic brain injury (TBI) is a devastating public health problem that may result in hypopituitarism. However, the mechanisms responsible for hypothalamic–pituitary dysfunction due to TBI are still unclear. Although the antibodies against neurons have been demonstrated in injured animal studies, investigations regarding the occurrence of antipituitary antibodies (APAs) in patients with TBI are lacking in the literature. In order to investigate whether autoimmune mechanisms could play a role in the pituitary dysfunction after TBI, we have planned this study aimed at investigating the presence of APA at the third year of TBI and association between the TBI-induced hypopituitarism and APA.Patients and designTwenty-nine (25 males and 4 females; age 36.5±2.3 years) patients who had completed a 3-year follow-up after TBI were included in the present study. APA and pituitary function were evaluated in all the patients 3 years after TBI; moreover, APAs were tested also in sera of 60 age-/sex-matched normal controls. The APAs were investigated by an indirect immunofluorescence method.ResultsAPAs were detected in 13 out of the 29 TBI patients (44.8%), but in none of the normal controls. Pituitary dysfunction development ratio was significantly higher in APA-positive patients (46.2%) when compared with APA-negative ones (12.5%;P=0.04). There was a significant association between APA positivity and hypopituitarism due to TBI (odds ratio: 2.25, 95% confidence intervals 1.1–4.6). Moreover, there was a significant positive correlation (r=0.74,P=0.004) between APA titer ratio and peak GH response to GHRH+GH related peptide (GHRP)-6 test, suggesting that high APA titers were associated with low GH response to GHRH+GHRP-6 test.ConclusionsThis study shows for the first time the presence of the APA in TBI patients 3 years after head trauma. Moreover, present investigation indicates preliminary evidence that APA may be associated with the development of TBI-induced pituitary dysfunction, thus suggesting that autoimmunity may contribute in the development of TBI-induced hypopituitarism. The presence of the association between APA and TBI-induced hypopituitarism may provide a new point of view in this field and promote further clinical and experimental studies.
Homozygous and heterozygous expression of a novel mutation of the acid-labile subunit
Authors: van Duyvenvoorde H A , Kempers M J E , Twickler Th B , van Doorn J , Gerver W J , Noordam C , Losekoot M , Karperien M , Wit J M , Hermus A R M M 
Published: May 2008

ContextAcid-labile subunit (ALS) deficiency due to homozygous inactivation of the ALS gene (IGFALS) is associated with moderate short stature, and in few cases pubertal delay. The clinical expression of heterozygosity is unknown.ObjectiveTo investigate the clinical, laboratory, and radiological features of homozygous and heterozygous carriers of a novel mutation in the ALS gene in comparison with non-carriers.SubjectsThree short Kurdish brothers and their relatives.ResultsThe index cases presented with short stature, microcephaly, and low circulating IGF-I and IGF-binding protein-3 (IGFBP-3), and undetectable ALS levels. Two were known with a low bone mineral density and one of them had suffered from two fractures. We found a novel homozygous ALS gene mutation resulting in a premature stop codon (c.1490dupT, p.Leu497PhefsX40). The IGF-I, IGFBP-3, and ALS 150 kDa ternary complex was absent, and ALS proteins in serum were not detected with western blot. IGFPB-1 and IGFPB-2 were low and there was a mild insulin resistance. Five heterozygous carriers tended to have a lower height and head circumference than five non-carriers, and had low plasma ALS and IGFBP-3 levels. Bone mineral (apparent) density was low in two out of three homozygous carriers, and also in four out of nine relatives.ConclusionsThe clinical presentation of homozygous ALS mutations may, besides short stature, include microcephaly. Heterozygous carriers may have less statural and head growth, suggestive for a gene dosage effect.
Comparison of bone mineral density and body proportions between women with complete androgen insensitivity syndrome and women with gonadal dysgenesis
Authors: Han T S , Goswami D , Trikudanathan S , Creighton S M , Conway G S 
Published: May 2008

ObjectivesTo compare bone mineral density (BMD) and body proportions between women with complete androgen insensitivity syndrome (CAIS) and with gonadal dysgenesis (GD).SettingAdult Disorders of Sexual Development and Ovarian Failure Clinics at University College London Hospitals.DesignRetrospective cross-sectional study of three groups of women aged 17–58 years with varying degrees of exposure to sex hormones and different combinations of sex chromosomes. Forty-six subjects had CAIS, 18 had GD and 46,XY (GD(XY)), and 25 had GD and 46,XX (GD(XX)). In addition, body proportions of subgroups of these women were analysed.Outcome measuresOestrogen therapy, karyotype, anthropometry and BMD.ResultsHeight differed between groups (F ratio 5.2, P=0.007)), with GD(XX) women being the shortest (mean±s.d.: 1.66±0.10 m), GD(XY) women the tallest (1.74±0.09 m) and CAIS women were in-between (1.70±0.07 m). Delayed gonadectomy resulted in taller stature in CAIS women (P=0.011). The ratio of lower to upper body length in GD(XY) women was significantly (P=0.001) greater than that of CAIS women. Multivariate logistic regression analysis (adjusted for age and height) showed that among women with XY karyotype, GD(XY) women were 5.2 times (95% confidence interval (CI): 1.3–20.1, P=0.018) more likely than CAIS women to have a low hip BMD. This difference was not evident among women with GD of different karyotypes (P=0.938). Spinal BMD did not differ between subject groups. Further adjustment for oestrogen replacement did not alter these relationships.ConclusionsTaller stature in late gonadectomised CAIS women suggests an oestrogen deficiency in these women prior to gonadectomy. Increased lower to upper body ratio in GD(XY) women compared with the other groups implies that these subjects have the greatest degree of oestrogen deficiency in puberty. Androgen rather than sex chromosomes may play an important role in cortical bone mineralisation in CAIS women, probably via estrogen receptor-α either directly or via aromatisation during critical periods of growth prior to gonadectomy.
Comparison of Temperature Data Collected from Artificial Chinook Salmon Redds and Surface Water in the Snake River
Authors: Groves Phillip A. , Chandler James A. , Richter Tracy J. 
Published: May 2008

Abstract
During three incubation periods, we collected temperature data from within artificial redds constructed in known spawning locations of Chinook salmon Oncorhynchus tshawytscha and from the surface water of the Snake River. Our objectives were to compare the data to determine (1) whether estimates of fry emergence timing differed between the two environments and (2) whether surface water data could be used to predict thermal conditions within redds. Statistical tests indicated that no differences could be detected between accumulated thermal units calculated from intraredd and surface water data (all P ≥ 0.06). We observed very little diel thermal fluctuation or daily difference within and between environments. Regression of intraredd temperature on surface water temperature was significant (r2 ≥ 0.98; all P &lt; 0.01), indicating that surface water temperature data can be used to predict intraredd temperature. We conclude that it is feasible to use surface water temperature as a surrogate for intraredd temperature in estimating Chinook salmon embryo developmental timing within the Snake River and potentially in other large rivers.
Large Woody Debris Structures and Their Influence on Atlantic Salmon Spawning in a Stream in Nova Scotia, Canada
Authors: MacInnis Charles , Floyd Trevor A. , Taylor Barry R. 
Published: May 2008

Abstract
Although large woody debris from streamside vegetation has profound influences on channel morphology and habitat for salmonid fishes, it has often been depleted by channelization or deforestation of the riparian zone. We installed artificial structures mimicking naturally fallen trees in a third-order stream in northern Nova Scotia from 1992 to 2004 to determine whether the structures enhanced spawning success of Atlantic salmon Salmo salar. In total, 250 digger logs (which mimic fallen tree trunks and stimulate formation of pools) and bank deflectors (which encourage meandering) were constructed in degraded reaches of Brierly Brook beginning at the downstream end. We monitored spawning each year by counting redds during the fall spawning season. Spawning rates (redd counts) in the whole brook increased exponentially for the first 4 years after restoration work began, from 43 in 1992 to 592 in 1996. By 1996, the entire length of Brierly Brook contained redds, and Atlantic salmon were using gravel that accumulated behind digger logs to build redds. Thereafter, redd counts remained high (502–605) but no longer increased, suggesting that restoration near the mouth of the brook removed an impediment to upstream migration. In 2004, reaches with artificial structures had significantly more redds (336) than reaches without the structures (280). In reaches with artificial structures, 48% of the redds were associated with gravel pool tails or the heads of riffles, 44% were near artificial structures, and 7% were near natural large woody debris. In reaches without artificial structures, almost 89% of the redds were associated with pool tails and the remainder were associated with natural large woody debris. Large woody debris, whether natural or artificial, appears to be an important source of spawning habitat for Atlantic salmon. Artificial structures mimicking naturally fallen wood are effective in the restoration of spawning habitat.
Subcellular distribution and potential detoxification mechanisms of mercury in the liver of the javan mongoose (Herpestes javanicus) in amamioshima Island, Japan
Authors: Horai Sawako , Furukawa Tatsuhiko , Ando Tetsuo , Akiba Suminori , Takeda Yasuo , Yamada Katsushi , Kuno Katsuji , Abe Shintaro , Watanabe Izumi 
Published: May 2008

Abstract
In a previous study, we showed that Hg accumulated to high levels in the liver of the Javan mongoose (Herpestes javanicus), a terrestrial mammal that lives on Amamioshima Island, Japan. This suggests a sophisticated mechanism of hepatic Hg detoxication. Assay of the subcellular localization of Hg and the expression of protective enzymes provides important clues for elucidating the mechanism of Hg detoxication. In the present study, the concentrations of 11 elements (Mg, Cr, Mn, Fe, Cu, Zn, Se, Rb, Cd, total Hg [T-Hg] and organic Hg [O-Hg], and Pb) were determined in the liver and in five liver subcellular fractions (plasma membrane, mitochondria, nuclei, microsome, and cytosol) of this species. As the T-Hg level increased, T-Hg markedly distributed to the plasma membrane. The T-Hg levels in all subcellular fractions correlated with Se levels. Although the T-Hg level in the microsomal fraction was relatively low, the ratio of O-Hg to T-Hg was significantly lower in the microsomes than in the other fractions. Significant positive correlations were found between the level of glutathione-S-transferase-π, a marker of oxidative stress, and the O-Hg and T-Hg levels, but the correlation was better with O-Hg than with T-Hg. Western blot analysis of thioredoxin reductase 2 (TrxR2), a protein involved in protecting cells from mitochondrial oxidative stress, showed that the level of TrxR2 correlated with that of T-Hg. High TrxR2 levels may be one mechanism by which the Javan mongoose attenuates the toxicity of the high Hg levels present in the liver.
Toxicity of the pesticide alpha-cypermethrin to four soil nontarget invertebrates and implications for risk assessment
Authors: Hartnik Thomas , Sverdrup Line E , Jensen John 
Published: May 2008

AbstractAlpha-cypermethrin, a synthetic pyrethroid, is used as an insecticide in agricultural settings and is increasingly replacing organophosphates and carbamates because of lower application rates and lower toxicity to mammals. Because very little is known about the acute and chronic toxicity of this compound for soil-living organisms, the present study investigated acute and sublethal toxicity of alpha-cypermethrin for four terrestrial invertebrate species in an agricultural soil from Norway. Bioassays with the earthworm Eisenia fetida, the potworm Enchytraeus crypticus, the springtail Folsomia candida, and the land snail Helix aspersa were performed according to slightly modified versions of Organization for Economic Cooperation and Development (Paris, France) or International Organization for Standardization (Geneva, Switzerland) guidelines and resulted in median lethal concentrations of greater than &gt;1,000 to 31.4 mg/kg and sublethal no-observed-effect concentrations of 2.51 to 82 mg/kg. A high acute to chronic ratio was found, especially in the earthworms. Interspecies differences in sensitivity may be explained by differences in exposure and differences in metabolization rate. When based on measured pore-water concentrations, terrestrial species overall appear to be approximately one order of magnitude less sensitive than aquatic species. Effect assessments conducted according to European guideline for risk assessment of pesticides reveal that assessments based on acute toxicity tests are not always conservative enough to determine environmentally safe concentrations in soil. Mandatory incorporation of sublethal toxicity data will ensure that in regions with temperate climate, the effects of pesticides on populations of soil-living organisms are unlikely.