bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone Mineral Density and Serum Levels of Soluble Tumor Necrosis Factors, Estradiol, and Osteoprotegerin in Postmenopausal Women with Cirrhosis after Viral Hepatitis
Authors: González-Calvin Jorge L. , Mundi Jose L. , Casado-Caballero Francisco J. , Abadia Ana C. , Martin-Ibañez Jose J. 
Published: November 2009

Context: Cirrhosis after viral hepatitis has been identified as a risk factor for osteoporosis in men. However, in postmenopausal women, most studies have evaluated the effect of primary biliary cirrhosis, but little is known about the effect of viral cirrhosis on bone mass [bone mineral density (BMD)] and bone metabolism.
Objective: Our objective was to assess the effect of viral cirrhosis on BMD and bone metabolism in postmenopausal women.
Design: We conducted a cross-sectional descriptive study.
Setting and Patients: We studied 84 postmenopausal female outpatients with viral cirrhosis and 96 healthy postmenopausal women from the general community. BMD was measured by dual-energy x-ray absorptiometry at lumbar spine (LS) and femoral neck (FN).
Results: The percentage with osteoporosis did not significantly differ between patients (LS, 43.1%; FN, 32.2%) and controls (LS, 41.2%; FN, 29.4%), and there was no difference in BMD (z-score) between groups. Serum concentrations of soluble TNF receptors, estradiol, and osteoprotegerin (OPG) were significantly higher in patients vs. controls (P &lt; 0.001, P &lt; 0.05, and P &lt; 0.05, respectively). No significant difference was observed in urinary deoxypyridinoline. Serum OPG levels were positively correlated with soluble TNF receptors (r = 0.35; P &lt; 0.02) and deoxypyridinoline (r = 0.37; P &lt; 0.05).
Conclusions: This study shows that bone mass and bone resorption rates do not differ between postmenopausal women with viral cirrhosis and healthy postmenopausal controls and suggests that viral cirrhosis does not appear to increase the risk of osteoporosis in these women. High serum estradiol and OPG concentrations may contribute to preventing the bone loss associated with viral cirrhosis in postmenopausal women.
High serum estradiol and osteoprotegerin concentrations may contribute to preventing the bone loss associated with viral cirrhosis in postmenopausal women.
Multifunctional Enhancers Regulate Mouse and Human Vitamin D Receptor Gene Transcription
Authors: Zella Lee A. , Meyer Mark B. , Nerenz Robert D. , Lee Seong Min , Martowicz Melissa L. , Pike J. Wesley 
Published: November 2009

AbstractThe vitamin D receptor (VDR) mediates the endocrine actions of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and autoregulates the expression of its own gene in target cells. In studies herein, we used chromatin immunoprecipitation-chip analyses to examine further the activities of 1,25(OH)2D3 and to assess the consequences of VDR/retinoid X receptor heterodimer binding at the VDR gene locus. We also explored mechanisms underlying the ability of retinoic acid, dexamethasone, and the protein kinase A activator forskolin to induce VDR up-regulation as well. We confirmed two previously identified intronic 1,25(OH)2D3-inducible enhancers and discovered two additional regions, one located 6 kb upstream of the VDR transcription start site. Although RNA polymerase II was present at the transcription start site in the absence of 1,25(OH)2D3, it was strikingly up-regulated at both this site and at individual enhancers in its presence. 1,25(OH)2D3 also increased basal levels of H4 acetylation at these enhancers as well. Surprisingly, many of these enhancers were targets for CCAAT enhancer-binding protein-β and runt-related transcription factor 2; a subset also bound cAMP response element binding protein, retinoic acid receptor, and glucocorticoid receptor. Unexpectedly, many of these factors were resident at the Vdr gene locus in the absence of inducer, suggesting that they might contribute to basal Vdr gene expression. Indeed, small interfering RNA down-regulation of CCAAT enhancer-binding protein-β suppressed basal VDR expression. These regulatory activities of 1,25(OH)2D3, forskolin, and dexamethasone were recapitulated in MC3T3-E1 cells stably transfected with a full-length VDR bacterial artificial chromosome (BAC) clone-luciferase reporter gene. Finally, 1,25(OH)2D3 also induced accumulation of VDR and up-regulated H4 acetylation at conserved regions in the human VDR gene. These data provide important new insights into VDR gene regulation in bone cells.
SCF, BDNF, and Gas6 Are Regulators of Growth Plate Chondrocyte Proliferation and Differentiation
Authors: Hutchison Michele R. , Bassett Mary H. , White Perrin C. 
Published: November 2009

Abstract
We previously demonstrated that bovine epiphyseal chondrocytes separated by density gradient centrifugation differ in proliferative response to IGF-I and IGF-I receptor number. To identify novel modifiers of IGF-I action at the growth plate, we used microarray analyses to compare bovine hypertrophic and reserve zones and identified several receptors differentially expressed across the growth plate: NTRK2 [receptor for brain-derived neurotrophic factor (BDNF)], KIT [receptor for stem cell factor (SCF)], and MER and AXL [two receptors for growth arrest-specific 6 (Gas6)]. The corresponding ligands were tested for their ability to stimulate either proliferation of isolated chondrocytes or differentiation in ATDC5 cells. Each factor inhibited IGF-I-mediated proliferation in isolated chondrocytes by attenuating ERK1/2 activation. SCF, BDNF, Gas6, and C-type natriuretic peptide promoted differentiation in ATDC5 cells, each factor producing different expression patterns for collagen X, collagen 2, aggrecan, and lysyl oxidase. Whereas multiple factors stimulated ATDC5 differentiation, only IGF-I and high-dose insulin, out of several factors implicated in chondrocyte maturation, stimulated proliferation of isolated chondrocytes. IGF-I appears to be the primary proliferative signal in growth plate chondrocytes, whereas multiple factors including SCF, BDNF, and Gas6 regulate the pace of differentiation at the growth plate.
Autosomal recessive familial neurohypophyseal diabetes insipidus: onset in early infancy
Authors: Abu Libdeh Abdulsalam , Levy-Khademi Floris , Abdulhadi-Atwan Maha , Bosin Emily , Korner Mira , White Perrin C , Zangen David H 
Published: November 2009

BackgroundFamilial neurohypophyseal diabetes insipidus (FNDI), usually an autosomal dominant disorder, is caused by mutations in the arginine vasopressin (AVP)–neurophysin II preprohormone leading to aberrant preprohormone processing and gradual destruction of AVP-secreting cells. Patients typically present between 1 and 6 years of age with polyuria and polydipsia.ObjectiveClinical, biochemical, and genetic studies of three new cases of autosomal recessive FNDI presenting in early infancy.PatientsThree Palestinian cousins presented with failure to thrive, vomiting, irritability, and fever. The parents were asymptomatic. Patients developed hypernatremia (154–163 mmol/l) and serum hyperosmolality (>320 mOsm/kg), while urine osmolality remained between 73 and 229 mOsm/kg. Plasma AVP levels were low, and the posterior pituitary bright spot was absent on magnetic resonance imaging (MRI). All patients responded to desmopressin.ResultsPatients were homozygous and parents were heterozygous for microsatellite markers flanking the AVP gene. All patients were homozygous for the P26L (proline to leucine) substitution affecting mature AVP. A founder effect with the single original kindred carrying the P26L mutation was confirmed by microsatellite analysis, but patients in that family presented only at 2 years of age. In microsatellite analysis, the new kindred patients were not homozygous and did not share a single allele at the aquaporin 2 and vasopressin receptor-2 genes locuses.ConclusionThis is the first description of autosomal recessive FNDI presenting in the neonatal period. The unusual early clinical and radiological (MRI) presentation argues against gradual destruction of AVP-secreting neurons as the pathophysiological mechanism. Factors beside allelism of AVP-related genes must influence the age of FNDI presentation given the founder effect demonstrated for the P26L mutation.
Serum glucose and insulin are associated with QTc and RR intervals in nondiabetic elderly
Authors: van Noord Charlotte , Sturkenboom Miriam C J M , Straus Sabine M J M , Hofman Albert , Kors Jan A , Witteman Jacqueline C M , Stricker Bruno H Ch 
Published: November 2009

AimsTo study whether nondiabetic persons with impaired fasting serum glucose and hyperinsulinemia have QTc/QT interval prolongation and RR interval shortening in the electrocardiogram (ECG), and whether these were associated with an increased risk of sudden cardiac death.MethodsThis study consisted of two analyses. First, a cross-sectional analysis was used as part of the population-based Rotterdam Study including 1050 men and 1520 women (≥55 years) without diabetes mellitus. Participants in round 3 of the Rotterdam Study for whom an ECG and fasting serum glucose and fasting insulin measurements were available were eligible for the study. Participants using digoxin or QTc-prolonging drugs and participants with left ventricular hypertrophy and left and right bundle branch block were excluded. The endpoints of the study were the lengths of the QTc, QT, and RR intervals. The associations were examined by means of linear regression analysis. Secondly, in all 6020 participants of the Rotterdam Study with an ECG, the associations between the QTc, QT, and RR intervals and sudden cardiac death were examined by means of Cox regression analysis.ResultsOverall, there was a significant association between impaired fasting serum glucose and the QTc interval with an increase of 2.6 ms (95% confidence interval (CI): 0.3; 5.0) in those with fasting glucose >6 mmol/l. Hyperinsulinemia was also associated with QTc prolongation (3.0 ms (0.8; 5.3)) in those with fasting insulin ≥100 pmol/l. Impaired fasting glucose (IFG) and hyperinsulinemia were significantly associated with a decrease of the RR interval (−33.7 ms (−48.8; −18.6) and −44.4 ms (−58.7; −30.0) respectively). Participants in the fourth quartile of the QTc and QT intervals had a significantly increased risk of sudden cardiac death compared to participants in the first quartile (hazard ratio (HR) 2.87 (95% CI: 2.02–4.06); HR 3.05 (1.99–4.67) respectively). Furthermore, there was a significant inverse association between the fourth quartile of the RR interval compared to the first quartile and the risk of sudden cardiac death (HR 0.49 (0.34–0.80)).ConclusionIn this population-based study, we demonstrated that IFG and hyperinsulinemia are associated with a significantly increased QTc interval and with significant shortening of the RR interval, the latter probably due to an increased sympathetic activity. In addition, we demonstrated that both a prolonged QTc interval and a shortened RR interval are associated with an increased risk of sudden cardiac death.
Excision of an Active CACTA-Like Transposable Element From DFR2 Causes Variegated Flowers in Soybean [Glycine max (L.) Merr.]
Authors: Xu Min , Brar Hargeet K , Grosic Sehiza , Palmer Reid G , Bhattacharyya Madan K 
Published: November 2009

Abstract
Active endogenous transposable elements, useful tools for gene isolation, have not been reported from any legume species. An active transposable element was suggested to reside in the W4 locus that governs flower color in soybean. Through biochemical and molecular analyses of several revertants of the w4-m allele, we have shown that the W4 locus encodes dihydroflavonol-4-reductase 2 (DFR2). w4-m has arisen through insertion of Tgm9, a 20,548-bp CACTA-like transposable element, into the second intron of DFR2. Tgm9 showed high nucleic acid sequence identity to Tgmt*. Its 5′ and 3′ terminal inverted repeats start with conserved CACTA sequence. The 3′ subterminal region is highly repetitive. Tgm9 carries TNP1- and TNP2-like transposase genes that are expressed in the mutable line, T322 (w4-m). The element excises at a high frequency from both somatic and germinal tissues. Following excision, reinsertions of Tgm9 into the DFR2 promoter generated novel stable alleles, w4-dp (dilute purple flowers) and w4-p (pale flowers). We hypothesize that the element is fractured during transposition, and truncated versions of the element in new insertion sites cause stable mutations. The highly active endogenous transposon, Tgm9, should facilitate genomics studies specifically that relate to legume biology.
Recurrent Selection on the Winters sex-ratio Genes in Drosophila simulans
Authors: Kingan Sarah B , Garrigan Daniel , Hartl Daniel L 
Published: November 2009

Abstract
Selfish genes, such as meiotic drive elements, propagate themselves through a population without increasing the fitness of host organisms. X-linked (or Y-linked) meiotic drive elements reduce the transmission of the Y (X) chromosome and skew progeny and population sex ratios, leading to intense conflict among genomic compartments. Drosophila simulans is unusual in having a least three distinct systems of X chromosome meiotic drive. Here, we characterize naturally occurring genetic variation at the Winters sex-ratio driver (Distorter on the X or Dox), its progenitor gene (Mother of Dox or MDox), and its suppressor gene (Not Much Yang or Nmy), which have been previously mapped and characterized. We survey three North American populations as well as 13 globally distributed strains and present molecular polymorphism data at the three loci. We find that all three genes show signatures of selection in North America, judging from levels of polymorphism and skews in the site-frequency spectrum. These signatures likely result from the biased transmission of the driver and selection on the suppressor for the maintenance of equal sex ratios. Coalescent modeling indicates that the timing of selection is more recent than the age of the alleles, suggesting that the driver and suppressor are coevolving under an evolutionary “arms race.” None of the Winters sex-ratio genes are fixed in D. simulans, and at all loci we find ancestral alleles, which lack the gene insertions and exhibit high levels of nucleotide polymorphism compared to the derived alleles. In addition, we find several “null” alleles that have mutations on the derived Dox background, which result in loss of drive function. We discuss the possible causes of the maintenance of presence–absence polymorphism in the Winters sex-ratio genes.
Healing of Euchromatic Chromosome Breaks by Efficient de novo Telomere Addition in Drosophila melanogaster
Authors: Titen Simon W A , Golic Kent G 
Published: November 2009

Abstract
Previously, we observed that heterochromatic 4 and Y chromosomes that had experienced breakage in the male germline were frequently transmitted to progeny. Their behavior suggested that they carried functional telomeres. Here we show that efficient healing by de novo telomere addition is not unique to heterochromatic breaks.
Circulating Tumor Cells: Evolving Evidence and Future Challenges
Authors: Dotan Efrat , Cohen Steven J. , Alpaugh Katherine R. , Meropol Neal J. 
Published: November 2009

Abstract
Circulating tumor cells (CTCs) are rare malignant cells found in the peripheral blood that originate from the primary tumor or metastatic sites. New techniques have been developed to isolate and characterize these cells. CTC enumeration has been incorporated into different fields of oncology as a prognostic marker, a tool to monitor therapy response, and a method to understand basic tumor characteristics. This review covers the different techniques available for isolation of CTCs, the clinical utility of CTCs in breast, prostate, and colon cancer, and future directions in this field.
Prognostic Factors for Resected Non-Small Cell Lung Cancer with pN2 Status: Implications for Use of Postoperative Radiotherapy
Authors: Moretti Luigi , Yu David S. , Chen Heidi , Carbone David P. , Johnson David H. , Keedy Vicki L. , Putnam Joe B. , Sandler Alan B. , Shyr Yu , Lu Bo 
Published: November 2009

Abstract

Learning Objectives
After completing this course, the reader will be able to: Analyze the clinical trial data and controversies for the use of PORT in NSCLC.Identify populations of lung cancer patients that may benefit from PORT and describe the possible implications of factors such as ECE status for selecting patients in the N2 population.Debate the need for new well-designed, randomized trials.
This article is available for continuing medical education credit at CME.TheOncologist.com.

Background.
For non-small cell lung cancer (NSCLC) patients with pN2 status, the use of postoperative radiotherapy (PORT) remains controversial. Here, we investigated the association between different clinicopathological features and postoperative therapy and local control and survival in patients with resected pN2 NSCLC.

Methods.
We retrospectively analyzed 83 patients with pN2 NSCLC who underwent resection at Vanderbilt University Medical Center between 1994 and 2004. The relationship between 10 prognostic factors—gender, age at diagnosis, histology, tumor size, number of nodal stations involved, positive node number, surgical margin, extracapsular extension (ECE), and use of postoperative chemotherapy and PORT—and 2-year local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), recurrence-free survival (RFS), and overall survival (OS) rates was evaluated. Univariate and multivariate analyses were conducted using the Kaplan–Meier method and Cox proportional hazards ratios, respectively.

Results.
On univariate analysis, PORT was significantly associated with greater LRFS, RFS, and OS rates, whereas chemotherapy was associated with a trend toward a higher OS rate. Negative surgical margins were predictive of a higher OS rate, and negative ECE was associated with higher LRFS and RFS rates. On multivariate analysis, only PORT and negative ECE were associated with a higher LRFS rate. On subgroup analysis, in negative ECE patients, PORT was significantly associated with a higher OS rate.

Conclusions.
PORT is associated with a higher OS rate for patients with resected pN2 NSCLC with negative ECE but not with positive ECE. The absence of ECE may serve as a useful prognostic variable in the selection of pN2 NSCLC patients for PORT and warrants further investigation in randomized clinical trials.
Current Approach to Pediatric Soft Tissue Sarcomas
Authors: Merchant Melinda S. , Mackall Crystal L. 
Published: November 2009

Abstract

Learning Objectives
After completing this course, the reader will be able to: Describe the heterogeneous histologies of soft tissue sarcomas that may occur in pediatric and young adult patients.Explain biology, risk classification, prognosis, and rational clinical management of pediatric type and adult type soft tissue sarcomas.Discuss the ways in which the histology and stage of cancer are currently used to devise treatment plans and how monitoring subsets (such as subtype of sarcoma, adequacy of resection, age of patient, and duration of therapy) and trying novel agents may improve results in pediatric STS.
This article is available for continuing medical education credit at CME.TheOncologist.com.
The development of a new soft tissue lesion in an otherwise healthy child, adolescent, or young adult can present many challenges for pediatric or medical oncology teams. Although uncommon, the diagnosis of a soft tissue malignancy should always be considered in the differential diagnosis of persistent pain, even if no mass is palpable. The definitive diagnosis and treatment of a soft tissue mass is aided by timely scans, appropriate biopsy for anatomic and molecular pathology, and a treatment approach guided by the specific diagnosis. Because pediatric soft tissue sarcomas are rare, cooperative groups play a crucial role in defining the standard of care through retrospective series and well-designed prospective clinical trials. Enrollment of newly diagnosed patients in clinical studies should be encouraged in order to continue to improve outcomes and understanding of these rare tumors. This review focuses on the current recommendations for management of sarcomas that typically occur in the soft tissues of pediatric and young adult patients.
Relation of the Leu40Arg variant of glycoprotein IIIA to personal and family history of myocardial infarction
Authors: Līcis Normunds , Latkovskis Gustavs , Krivmane Baiba , Zabunova Milāna , Berzina Marina , Juhnevica Dace , Ērglis Andrejs 
Published: November 2009

Relation of the Leu40Arg variant of glycoprotein IIIA to personal and family history of myocardial infarction
GPIIb/IIIa fibrinogen receptor is a key element of the thrombotic pathway. In this study, we investigated the possible relation of PlA1/A2 polymorphism (1565T>C; Leu33Pro) and a rare 1586T>G (Leu40Arg) variation of GPIIIa gene to personal and family history of myocardial infarction (MI) among 601 patients with angiographically confirmed coronary heart disease. Four hundred and fifteen patients had MI and 94 of individuals reported family history of premature MI. The Arg40 (1586G) variant (n = 4) was present exclusively in MI-patients and significantly correlated with a family history of premature MI (P = 0.013), whereas the Pro33 (1565C; PlA2) allele (n = 204) was similarly prevalent among different groups of patients. These data indicate the importance of the Arg40 variant but do not support a significant role of Pro33 allele in susceptibility to MI.
Fast object detection in digital grayscale images
Authors: Lorencs Aivars , Mednieks Ints , Siņica-Siņavskis Juris 
Published: November 2009

Fast object detection in digital grayscale images
The problem of specific object detection in digital grayscale images is considered under the following conditions: relatively small image fragments can be analysed (a priori information about the size of objects is available); images contain a varying undefined background (clutter) of larger objects; processing time should be minimised and must be independent from the image contents; proposed methods should provide for efficient implementation in application-specific electronic circuits. The last two conditions reflect the aim to propose approaches suitable for application in real time systems where known sophisticated methods would be inapplicable. The research is motivated by potential applications in the food industry (detection of contaminants in products from their X-ray images), medicine (detection of anomalies in fragments of computer tomography images etc.). Possible objects to be detected may include compact small objects, curved lines in different directions, and small regions of pixels with brightness different from the background. The paper describes proposed image processing approaches to detection of such objects and the results obtained from processing of sample food images.
Alpha 1-atitrypsin deficiency: from genetic routes to bedside
Authors: Lāce Baiba , Krams Alvils , Pilāns Didzis , Krūmiņa Astrīda 
Published: November 2009

Alpha 1-atitrypsin deficiency: from genetic routes to bedside
Alpha 1-antitrypsin (A1AT) deficiency is a one of the most common genetic disorders in Caucasians. It is characterised by low serum levels of A1AT and a high risk of pulmonary emphysema and liver disease at a young age. The disease is caused by mutations in the SERPINA1 gene, which belongs to a cluster of protease inhibitor genes, with the main protein function of reducing the activity of serine-type endopeptidases, like neutrophil elastase. The most common mutation is E342K (Z), which is frequently found in northern Europeans. This mutation most probably arose in southern Sweden; however, the highest frequency of the Z mutation reported so far is in western Latvia. A1AT deficiency is not a widely recognised clinical problem. Disease onset most probably occurs in early adulthood with non-specific symptoms, like dyspnoea and recurrent pulmonary events, and it is triggered by certain risk factors, like smoking and working in an unfavourable environment.