bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Value of p16 in Locally Advanced Prostate Cancer: A Study Based on Radiation Therapy Oncology Group Protocol 9202
Authors: Chakravarti Arnab , DeSilvio Michelle , Zhang Min , Grignon David , Rosenthal Seth , Asbell Sucha O. , Hanks Gerald , Sandler Howard M. , Khor Li-Yan , Pollack Alan , Shipley William 
Published: July 2007

Purpose Deregulation of the retinoblastoma (RB) pathway is commonly found in virtually all known human tumors. p16, the upstream regulator of RB, is among the most commonly affected member of this pathway. In the present study, we examined the prognostic value of p16 expression in men with locally advanced prostate cancer who were enrolled on Radiation Therapy Oncology Group protocol 9202. Patients and Methods RTOG 9202 was a phase III randomized study comparing long-term (LT) versus short-term (ST) androgen-deprivation therapy (AD). Of the 1,514 eligible cases, 612 patients had adequate tumor material for p16 analysis. Expression levels of p16 were determined by immunohistochemistry (IHC). IHC staining was scored quantitatively using an image analysis system. Results On multivariate analysis, intact p16 expression was significantly associated with decreased rate of distant metastases (P = .0332) when both STAD and LTAD treatment arms were considered together. For patients with intact (high levels of immunostaining) p16 (mean p16 index > 81.3%), LTAD plus radiotherapy (RT) significantly improved prostate cancer survival (PCS) compared with STAD plus RT (P = .0008) and reduced the frequency of distant metastasis (P = .0069) compared with STAD plus RT. In contrast, for patients with tumors demonstrating p16 loss (low levels of immunostaining, mean p16 index ≤ 81.3%), LTAD plus RT significantly improved biochemical no evidence of disease survival over STAD (P < .0001) primarily by decreasing the frequency of local progression (P = .02), as opposed to distant metastasis, which was the case in the high-p16 cohort. Conclusion Low levels of p16 on image analysis appear to be associated with a significantly higher risk of distant metastases among all study patients. p16 expression levels also appear to identify patients with locally advanced prostate cancer with distinct patterns of failure after LTAD.
Impact of Primary Prophylaxis With Granulocyte Colony-Stimulating Factor on Febrile Neutropenia and Mortality in Adult Cancer Patients Receiving Chemotherapy: A Systematic Review
Authors: Kuderer Nicole M. , Dale David C. , Crawford Jeffrey , Lyman Gary H. 
Published: July 2007

Purpose Randomized controlled trials (RCTs) of prophylactic granulocyte colony-stimulating factors (G-CSF) have demonstrated a significant reduction in febrile neutropenia (FN) after systemic chemotherapy. Several RCTs have been published recently that investigate the impact of G-CSF on mortality and relative dose-intensity (RDI). Methods A comprehensive systematic review and meta-analysis of all reported RCTs comparing primary prophylactic G-CSF with placebo or untreated controls in adult solid tumor and malignant lymphoma patients was undertaken without language restrictions, using electronic databases, conference proceedings, and hand-searching techniques. Two reviewers extracted data independently. Summary estimates of relative risk (RR) with 95% CIs were estimated based on the method of Mantel-Haenszel and DerSimonian and Laird. Results Seventeen RCTs were identified including 3,493 patients. For infection-related mortality, RR reduction with G-CSF compared with controls was 45% (RR = 0.55; 95% CI, 0.33 to 0.90; P = .018); for early mortality (all-cause mortality during chemotherapy period), it was 40% (RR = 0.60; 95% CI, 0.43 to 0.83; P = .002); and for FN, it was 46% (RR = 0.54; 95% CI, 0.43 to 0.67; P < .001). Average RDI was significantly higher in patients who received G-CSF compared with control patients (P < .001). Bone or musculoskeletal pain was reported in 10.4% of controls and 19.6% of G-CSF patients (RR = 4.03; 95% CI, 2.15 to 7.52; P < .001). Significant reductions in FN with G-CSF were observed in studies allowing secondary G-CSF prophylaxis in controls and in the three trials with concurrent prophylactic antibiotics in both treatment arms. Conclusion Prophylactic G-CSF reduces the risk of FN and early deaths, including infection-related mortality, while increasing RDI and musculoskeletal pain. There are insufficient data to assess the impact of G-CSF on disease-free and overall survival.
Common Germline Genetic Variation in Antioxidant Defense Genes and Survival After Diagnosis of Breast Cancer
Authors: Udler Miriam , Maia Ana-Teresa , Cebrian Arancha , Brown Clement , Greenberg David , Shah Mitul , Caldas Carlos , Dunning Alison , Easton Douglas , Ponder Bruce , Pharoah Paul 
Published: July 2007

PurposeThe prognosis of breast cancer varies considerably among individuals, and inherited genetic factors may help explain this variability. Of particular interest are genes involved in defense against reactive oxygen species (ROS) because ROS are thought to cause DNA damage and contribute to the pathogenesis of cancer.Patients and MethodsWe examined associations between 54 polymorphisms that tag the known common variants (minor allele frequency > 0.05) in 10 genes involved in oxidative damage repair (CAT, SOD1, SOD2, GPX1, GPX4, GSR, TXN, TXN2, TXNRD1, and TXNRD2) and survival in 4,470 women with breast cancer.ResultsTwo single nucleotide polymorphisms (SNPs) in GPX4 ( rs713041 and rs757229 ) were associated with all-cause mortality even after adjusting for multiple hypothesis testing (adjusted P = .0041 and P = .0035). These SNPs are correlated with each other (r2= 0.61). GPX4 rs713041 is located near the selenocysteine insertion sequence element in the GPX4 3′ untranslated region, and the rare allele of this SNP is associated with an increased risk of death, with a hazard ratio of 1.27 per rare allele carried (95% CI, 1.13 to 11.43). This effect was not attenuated after adjusting for tumor stage, grade, or estrogen receptor status. We found that the common allele is preferentially expressed in normal lymphocytes, normal breast, and breast tumors compared with the rare allele, but there were no differences in total levels of GPX4 mRNA across genotypes.ConclusionThese data provide strong support for the hypothesis that common variation in GPX4 is associated with prognosis after a diagnosis of breast cancer.
Molecular Basis of Neonatal Diabetes in Japanese Patients
Authors: Suzuki Shigeru , Makita Yoshio , Mukai Tokuo , Matsuo Kumihiro , Ueda Osamu , Fujieda Kenji 
Published: July 2007

Abstract
Context: Neonatal diabetes mellitus (NDM) is classified clinically into a transient form (TNDM), in which insulin secretion recovers within several months, and a permanent form (PNDM), requiring lifelong medication. However, these conditions are genetically heterogeneous.
Objective: Our objective was to evaluate the contribution of the responsible gene and delineate their clinical characteristics.
Patients and Methods: The chromosome 6q24 abnormality and KCNJ11 and ABCC8 mutations were analyzed in 31 Japanese patients (16 with TNDM and 15 with PNDM). Moreover, FOXP3 and IPF1 mutations were analyzed in a patient with immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome and with pancreatic agenesis, respectively.
Results: A molecular basis for NDM was found in 23 patients: 6q24 in eleven, KCNJ11 in nine, ABCC8 in two, and FOXP3 in one. All the patients with the 6q24 abnormality and two patients with the KCNJ11 mutation proved to be TNDM. Five mutations were novel: two (p.A174G and p.C166Y) in KCNJ11, two (p.A90V and p.N1122D) in ABCC8, and one (p.P367L) in FOXP3. Comparing the 6q24 abnormality and KCNJ11 mutation, there were some significant clinical differences: the earlier onset of diabetes, the lower frequency of diabetic ketoacidosis at onset, and the higher proportion of the patients with macroglossia at initial presentation in the patients with 6q24 abnormality. In contrast, two patients with the KCNJ11 mutations manifested epilepsy and developmental delay.
Conclusions: Both the 6q24 abnormality and KCNJ11 mutation are major causes of NDM in Japanese patients. Clinical differences between them could provide important insight into the decision of which gene to analyze in affected patients first.
A Comparison of the Attitudes and Beliefs of Professional Rugby Players from one Club and Parents of Children Playing Rugby at an Adjacent Amateur Club to the Wearing of Mouthguards
Authors: Chatterjee Mahua , Hilton Ian 
Published: July 2007

Objective To assess the knowledge that professional rugby players have with regard to the benefits of wearing an oral mouth-guard and the importance that they give to wearing the appliance during play, then to compare these views with those of the parents of children who are beginning to play the sport. Design Questionnaires and covering letters were sent to the parents of children who played rugby at Malton & Norton Rugby Union Football Club (RUFC), which has teams for all age groups from under 7–8 years to adult. Similar questionnaires were sent to the first team squad of Leeds Tykes, a Zurich Premiership rugby union club. The questionnaires asked a series of questions on the use of mouthguards and knowledge of their importance in the prevention of injuries. Results The overall response rate was 76%. Seventy-four of the 100 questionnaires sent to the parents and 25 of the 30 sent to the professional players were completed and returned. Both the professional rugby players and parents felt that mouthguards were essential when playing rugby. The professionals seemed to have a much greater understanding of the benefits that mouth-guards provided. Although parents agreed that children should begin to wear mouthguards as soon as possible, very few actually did. The barriers to providing mouth protection were mainly financial combined with the difficulties of taking the child to the dentist. Conclusions If the results from this small study are representative of the current situation, with regard to the wearing of mouth-guards by professional players and children, it appears that there is a need for all those involved to ensure that rugby-playing children wear mouthguards. Rugby clubs could consider the appointment of honorary dental advisers and devise systems to ensure that cost is not a factor in preventing children from wearing mouthguards.
A Simple and Robust Quantitative PCR Assay to Determine CYP21A2 Gene Dose in the Diagnosis of 21-Hydroxylase Deficiency
Authors: Parajes Silvia , Quinterio Celsa , Domínguez Fernando , Loidi Lourdes 
Published: July 2007

Abstract
Background: Correct diagnosis of 21-hydroxylase deficiency (21OHD) requires the identification of CYP21A2 gene deletions and CYP21A1P/CYP21A2 chimeric genes, which are disease-causing alleles, and gene duplications, which can lead to false-positive 21OHD allele results. Because lack of suitable CYP21A2 dosage assessment methods hampers correct 21OHD diagnosis, we developed a new assay based on the relative quantification of the CYP21A2 gene using the DSP gene as a reference.
Methods: The assay to determine CYP21A2 copy number is based on real-time PCR. The method also detects the presence of the CYP21A1P/CYP21A2 chimeric gene. We used a duplex PCR to coamplify the DSP gene, included as an internal control, along with CYP21A2. The difference in threshold cycles between CYP21A2 and DSP genes (ΔCt) was used to assess CYP21A2 copy number.
Results: The ΔCt values obtained from 24 samples used to set up the method clearly differentiated 3 nonoverlapping intervals, which corresponded to the number of CYP21A2 copies: −1.35 to −0.25 defined 2 gene copies, +0.20 to +2.00 defined 1 copy, and −2.50 to −1.50 defined 3 copies. With these intervals we were able to assess the gene copy number in 24 additional samples.
Conclusions: This new method for gene copy assessment detects homozygous and heterozygous CYP21A2 gene deletions, CYP21A1P/CYP21A2 chimeric genes, and gene duplications. Moreover, the method is robust, fast, and easy to use in a molecular diagnosis laboratory. This method together with CYP21A2 gene sequencing can provide a definitive system for the detection of almost all, common as well as rare, 21OHD alleles.
Characterization of Diabetic Nephropathy by Urinary Proteomic Analysis: Identification of a Processed Ubiquitin Form as a Differentially Excreted Protein in Diabetic Nephropathy Patients
Authors: Dihazi Hassan , Müller Gerhard A , Lindner Sandra , Meyer Markus , Asif Abdul R , Oellerich Michael , Strutz Frank 
Published: July 2007

Abstract
Background: Identification of markers for prediction of the clinical course of diabetic nephropathy remains a major challenge in disease management. We established a proteomics approach for identification of diabetic nephropathy-related biomarkers in urine.
Methods: We used SELDI-TOF mass spectrometry and SAX2 protein arrays to compare protein profiles from urine of 4 defined patient groups. Samples from patients with type 2 diabetes (DM; n = 45) without nephropathy and without microalbuminuria (DM-WNP), patients with DM with macro- or microalbuminuria (DM-NP; n = 38), patients with proteinuria due to nondiabetic renal disease (n = 34), and healthy controls (n = 45) were analyzed. Anionic exchange, reversed-phase fractionation, gel electrophoresis, and mass spectrometry were used to isolate and identify proteins with high discriminatory power.
Results: A protein with m/z 6188 (P &lt;0.0000004) was strongly released in the urine of healthy controls, patients with proteinuria due to nondiabetic disease, and DM-WNP in contrast to DM-NP patients. An m/z 14 766 protein (P &lt;0.00008) was selectively excreted in the urine of DM-NP patients, whereas the protein with m/z 11 774 (P &lt;0.000004) was significantly excreted by patients with proteinuria and DM-NP. The m/z 11 774 and m/z 14 766 mass peaks were identified as β2-microglobulin and UbA52, a ubiquitin ribosomal fusion protein, respectively. The protein with m/z 6188 was identified as a processed form of ubiquitin.
Conclusion: The release of high amounts of UbA52 in urine of DM-NP patients could serve as a diagnostic marker, whereas the lack of the short form of ubiquitin raises interesting questions about the pathophysiology.
The Paleoproterozoic megascopic Stirling biota
Authors: Bengtson Stefan , Rasmussen Birger , Krapež Bryan 
Published: July 2007

AbstractThe 2.0–1.8-billion-year-old Stirling Range Formation in southwestern Australia preserves the deposits of a siliciclastic shoreline formed under the influence of storms, longshore currents, and tidal currents. Sandstones contain a megascopic fossil biota represented by discoidal fossils similar to the EdiacaranAspidellaBillings, 1872, as well as ridge pairs preserved in positive hyporelief on the soles of channel-fill sandstones bounded by mud drapes. The ridges run parallel or nearly parallel for most of their length, meeting in a closed loop at one end and opening with a slight divergence at the opposite end. The ridges are interpreted as casts of sediment-laden mucus strings formed by the movement of multicellular or syncytial organisms along a muddy surface. The taxaMyxomitodes stirlingensisn. igen., n. isp., are introduced for these traces. The Stirling biota was roughly coeval with other presumed multicellular eukaryotes appearing after a long period of profound environmental changes involving a rise in ambient oxygen levels, similar to that which preceded the Cambrian explosion. The failure of multicellular life to diversify during most of the Proterozoic may be due to environmental constraints related to the comparatively low level of oxidation of the world oceans.
Reduced Surface Runoff Losses of Metolachlor in Narrow‐Row Compared to Wide‐Row Soybean
Authors: Krutz L. Jason , Koger Clifford H. , Locke Martin A. , Steinriede Robert W. 
Published: July 2007

AbstractCultural management practices that reduce the off‐site transport of herbicides applied to row crops are needed to protect surface water quality. A soybean [Glycine max (L.) Merr.] field study was conducted near Stoneville, MS on Sharkey clay to evaluate row spacing (50 cm vs. 100 cm) effects on metolachlor [2‐chloro‐N‐(2‐ethyl‐6‐methylphenyl)‐N‐(methoxy‐1‐methylethyl) acetamide] transport. One day after the foliar application of metolachlor to 2.03 m wide by 2.43 m long plots, 60 mm h−1 of simulated rainfall was applied until 25 min of runoff was generated per plot. The calculated mass of metolachlor intercepted by the soybean foliage was greater in narrow‐row than wide‐row soybean, 0.39 kg ha−1 vs. 0.23 kg ha−1, respectively. Field and laboratory studies indicated that less than 2% of the metolachlor intercepted by the soybean foliage was available for foliar wash‐off 1 d after application. Antecedent soil water content at the start of the simulations was lower in narrow‐row soybean. In turn, there was a 1.7‐fold greater time to runoff on narrow‐row plots. The greater time to runoff likely contributed to lower metolachlor concentration in runoff from narrow‐row plots. Cumulative metolachlor losses were significantly greater in wide‐row than narrow‐row soybean, 3.7% vs. 2.2%, respectively. Findings indicate that narrow‐row planting systems may reduce metolachlor runoff following a post‐emergence application.
Is Sanfilippo type B in your mind when you see adults with mental retardation and behavioral problems?
Authors: Moog Ute , van Mierlo Ingrid , van Schrojenstein Lantman‐de Valk Henny M.J. , Spaapen Leo , Maaskant Marian A. , Curfs Leopold M.G. 
Published: July 2007

AbstractSanfilippo type B is an autosomal recessive mucopolysaccharidosis (MPS IIIB) caused by deficiency of N‐acetyl‐α‐D‐glucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulfate. It is characterized by neurologic degeneration, behavioral problems, and mental decline. Somatic features are relatively mild and patients with this disorder can reach late adulthood. It is the most common subtype of MPS in the Netherlands and probably underdiagnosed in adult persons with mental retardation (MR). In order to increase knowledge on the adult phenotype and natural history in Sanfilippo type B, we present the clinical data of 20 patients with this disorder. Sixteen of them were followed for one to three decades. Six died between 28 and 69 years of age, mainly from pneumonia and cachexia; the surviving patients were 18–63 years old. Apart from the youngest, they had lost mobility at 36–68 years. Most had developed physical problems, in particular in the 4th–6th decade of life: cardiac disease (cardiomyopathy, atrial fibrillations), arthritis, skin blistering, swallowing difficulties requiring feeding by a gastrostomy tube, and seizures. The course of the disease was dominated in most of them by challenging behavioral problems with restlessness, extreme screaming and hitting, difficult to prevent or to treat pharmaceutically. Even in absence of knowledge of the history of an elderly patient with MR, the presence of behavioral problems should prompt metabolic investigation for MPS. © 2007 Wiley‐Liss, Inc.
Liquid chromatographic analysis of certain commercial formulations for non‐opioid analgesics
Authors: Bhushan R. , Gupta Deepak , Mukherjee Aparna 
Published: July 2007

AbstractA simple and sensitive method for separation and quantitative determination of non‐opioid analgesics from pharmaceutical preparations has been developed and validated. Commercial formulations of three non‐opioid analgesics, viz. paracetamol, ibuprofen and diclofenac, were chosen for present studies. These were extracted, isolated, purified and recrystallized and were characterized by melting point, λmax and IR. Quantitative determination was carried out using HPLC and TLC supplemented with UV spectrophotometry. Copyright © 2007 John Wiley & Sons, Ltd.
A rapid and highly sensitive method for the determination of glimepiride in human plasma by liquid chromatography–electrospray ionization tandem mass spectrometry: application to a pre‐clinical pharmacokinetic study
Authors: Chakradhar Lagishetty , Kallem Rajareddy , Karthik Arumugam , Sundari Bala Tripura , Ramesh Srirangam , Mullangi Ramesh , Srinivas Nuggehally R. 
Published: July 2007

AbstractA sensitive and specific liquid chromatography–positive electrospray ionization–tandem mass spectrometry method has been developed and validated for the determination of glimepiride (GPD) in human plasma. GPD and the internal standard (IS, glibenclamide) were extracted from a small aliquot of human plasma (200 µL) by a simple liquid–liquid extraction technique using ethyl acetate as extraction solvent. The compounds were separated on a YMC Propack, C18, 4.6 × 50 mm column using a mixture of ammonium acetate buffer, acetonitrile and methanol (30:60:10, v/v) as mobile phase at 0.5 mL/min on an API 4000 Sciex mass spectrometer connected to an Agilent HPLC system. Method validation and pre‐clinical sample analysis was performed as per FDA guidelines and the results met the acceptance criteria. GPD and IS were detected without any interference from human plasma matrix. The method was proved to be accurate and precise at linearity range of 0.02–100.00 ng/mL with a correlation coefficient of 0.999. The method was robust with a lower limit of quantitation of 0.02 ng/mL. Intra‐ and inter‐day accuracies for GPD were 88.60–113.50 and 96.82–103.93%, respectively. The inter‐day precision was better than 12.21%. This method enabled faster and reliable determination of GPD in a pre‐clinical study. Copyright © 2007 John Wiley & Sons, Ltd.
Structure–Fluorescence Contrast Relationship in Cyanine DNA Intercalators: Toward Rational Dye Design
Authors: Fürstenberg Alexandre , Deligeorgiev Todor G. , Gadjev Nikolai I. , Vasilev Aleksey A. , Vauthey Eric 
Published: July 2007

AbstractThe fluorescence enhancement mechanisms of a series of DNA stains of the oxazole yellow (YO) family have been investigated in detail using steady‐state and ultrafast time‐resolved fluorescence spectroscopy. The strong increase in the fluorescence quantum yield of these dyes upon DNA binding is shown to originate from the inhibition of two distinct processes: 1) isomerisation through large‐amplitude motion that non‐radiatively deactivates the excited state within a few picoseconds and 2) formation of weakly emitting H‐dimers. As the H‐dimers are not totally non‐fluorescent, their formation is less efficient than isomerisation as a fluorescent contrast mechanism. The propensity of the dyes to form H‐dimers and thus to reduce their fluorescence contrast upon DNA binding is shown to depend on several of their structural parameters, such as their monomeric (YO) or homodimeric (YOYO) nature, their substitution and their electric charge. Moreover, these parameters also have a substantial influence on the affinity of the dyes for DNA and on the ensuing sensitivity for DNA detection. The results give new insight into the development and optimisation of fluorescent DNA probes with the highest contrast.