bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advanced Breast Cancer and Breast Cancer Mortality in Randomized Controlled Trials on Mammography Screening
Authors: Autier Philippe , Héry Clarisse , Haukka Jari , Boniol Mathieu , Byrnes Graham 
Published: November 2009

PurposeWe assessed changes in advanced cancer incidence and cancer mortality in eight randomized trials of breast cancer screening.Patients and MethodsDepending on published data, advanced cancer was defined as cancer ≥ 20 mm in size (four trials), stage II+ (four trials), and ≥ one positive lymph node (one trial). For each trial, we obtained the estimated relative risk (RR) and 95% CI between the intervention and control groups, for both breast cancer mortality and diagnosis of advanced breast cancer. Using a meta-regression approach, log(RR-mortality) was regressed on log(RR-advanced cancer), weighting each trial by the reciprocal of the square of the standard error of log(RR) for mortality.ResultsRR for advanced breast cancer ranged from 0.69 (95% CI, 0.61 to 0.78) in the Swedish Two-County Trial to 0.97 (95% CI, 0.97 to 1.25) in the Canadian National Breast Screening Study-1 (NBSS-1) trial. Log(RR)s for advanced cancer were highly predictive of log(RR)s for mortality (R2= 0.95; P < .0001), and the linear regression curve had a slope of 1.00 (95% CI, 0.76 to 1.25) after fixing the intercept to zero. The slope changed only slightly after excluding the Two-County Trial and the Canadian NBSS-1 and NBSS-2 trials.ConclusionIn trials on breast cancer screening, for each unit decrease in incidence of advanced breast cancer, there was an equal decrease in breast cancer mortality. Monitoring of incidence of advanced breast cancer may provide information on the current impact of screening on breast cancer mortality in the general population.
Melanoma Prognostic Model Using Tissue Microarrays and Genetic Algorithms
Authors: Gould Rothberg Bonnie E. , Berger Aaron J. , Molinaro Annette M. , Subtil Antonio , Krauthammer Michael O. , Camp Robert L. , Bradley William R. , Ariyan Stephan , Kluger Harriet M. , Rimm David L. 
Published: November 2009

Purpose As a result of the questionable risk-to-benefit ratio of adjuvant therapies, stage II melanoma is currently managed by observation because available clinicopathologic parameters cannot identify the 20% to 60% of such patients likely to develop metastatic disease. Here, we propose a multimarker molecular prognostic assay that can help triage patients at increased risk of recurrence. Methods Protein expression for 38 candidates relevant to melanoma oncogenesis was evaluated using the automated quantitative analysis (AQUA) method for immunofluorescence-based immunohistochemistry in formalin-fixed, paraffin-embedded specimens from a cohort of 192 primary melanomas collected during 1959 to 1994. The prognostic assay was built using a genetic algorithm and validated on an independent cohort of 246 serial primary melanomas collected from 1997 to 2004. Results Multiple iterations of the genetic algorithm yielded a consistent five-marker solution. A favorable prognosis was predicted by ATF2 ln(non-nuclear/nuclear AQUA score ratio) of more than –0.052, p21WAF1 nuclear compartment AQUA score of more than 12.98, p16INK4A ln(non-nuclear/nuclear AQUA score ratio) of ≤ −0.083, β-catenin total AQUA score of more than 38.68, and fibronectin total AQUA score of ≤ 57.93. Primary tumors that met at least four of these five conditions were considered a low-risk group, and those that met three or fewer conditions formed a high-risk group (log-rank P < .0001). Multivariable proportional hazards analysis adjusting for clinicopathologic parameters shows that the high-risk group has significantly reduced survival on both the discovery (hazard ratio = 2.84; 95% CI, 1.46 to 5.49; P = .002) and validation (hazard ratio = 2.72; 95% CI, 1.12 to 6.58; P = .027) cohorts. Conclusion This multimarker prognostic assay, an independent determinant of melanoma survival, might be beneficial in improving the selection of stage II patients for adjuvant therapy.
Multimodality Screening of High-Risk Women: A Prospective Cohort Study
Authors: Weinstein Susan P. , Localio A. Russell , Conant Emily F. , Rosen Mark , Thomas Kathleen M. , Schnall Mitchell D. 
Published: November 2009

Purpose Mammography has been established as the primary imaging screening method for breast cancer; however, the sensitivity of mammography is limited, especially in women with dense breast tissue. Given the limitations of mammography, interest has developed in alternative screening techniques. This interest has led to numerous studies reporting mammographically occult breast cancers detected on magnetic resonance imaging (MRI) or ultrasound. In addition, digital mammography was shown to be more sensitive than film mammography in selected populations. Our goal was to prospectively compare cancer detection of digital mammography (DM), whole-breast ultrasound (WBUS), and contrast-enhanced MRI in a high-risk screening population previously screened negative by film screen mammogram (FSM). Methods During a 2-year period, 609 asymptomatic high-risk women with nonactionable FSM examinations presented for a prospective multimodality screening consisting of DM, WBUS, and MRI. The FSM examinations were reinterpreted by study radiologists. Patients had benign or no suspicious findings on clinical examination. The cancer yield by modality was evaluated. Results Twenty cancers were diagnosed in 18 patients (nine ductal carcinomas in situ and 11 invasive breast cancers). The overall cancer yield on a per-patient basis was 3.0% (18 of 609 patients). The cancer yield by modality was 1.0% for FSM (six of 597 women), 1.2% for DM (seven of 569 women), 0.53% for WBUS (three of 567 women), and 2.1% for MRI (12 of 571 women). Of the 20 cancers detected, some were only detected on one imaging modality (FSM, n = 1; DM, n = 3; WBUS, n = 1; and MRI, n = 8). Conclusion The addition of MRI to mammography in the high-risk group has the greatest potential to detect additional mammographically occult cancers. The incremental cancer yield of WBUS and DM is much less.
Unique Localization of Circulating Tumor Cells in Patients With Hepatic Metastases
Authors: Jiao Long R. , Apostolopoulos Christos , Jacob Jimmy , Szydlo Richard , Johnson Natalia , Tsim Nicole , Habib Nagy A. , Coombes R. Charles , Stebbing Justin 
Published: November 2009

Purpose There are few data on the impact of immediate and differing surgical interventions on circulating tumor cells (CTCs), nor their compartmentalization or localization in different anatomic vascular sites. Patients and Methods CTCs from consecutive patients with colorectal liver metastases were quantified before and immediately after open surgery, laparoscopic resection, open radiofrequency ablation (RFA), or percutaneous RFA. For individuals undergoing open surgery, either hepatic resections or open RFA, CTCs were examined in both systemic and portal circulation by measuring CTCs in samples derived from the peripheral vein, an artery, the hepatic portal vein, and the hepatic vein. Results A total of 29 consecutive patients with colorectal liver metastases with a median age of 55 years (range, 30 to 88 years) were included. CTCs were localized to the hepatic portosystemic macrocirculation with significantly greater numbers than in the systemic vasculature. Surgical procedures led to a statistically significant fall in CTCs at multiple sites measured. Conversely, RFA, either open or percutaneous, was associated with a significant increase in CTCs. Conclusion Surgical resection of metastases, but not RFA, immediately decreases CTC levels. In patients with colorectal liver metastases, CTCs appear localized to the hepatic (and pulmonary) macrocirculations. This may explain why metastases in sites other than the liver and lungs are infrequently observed in cancer.
Glucocorticoids in Vivo Induce Both Insulin Hypersecretion and Enhanced Glucose Sensitivity of Stimulus-Secretion Coupling in Isolated Rat Islets
Authors: Rafacho Alex , Marroquí Laura , Taboga Sebastião R. , Abrantes Júlia L. F. , Silveira Leonardo R. , Boschero Antonio C. , Carneiro Everardo M. , Bosqueiro José R. , Nadal Angel , Quesada Ivan 
Published: October 2009

AbstractAlthough glucocorticoids are widely used as antiinflammatory agents in clinical therapies, they may cause serious side effects that include insulin resistance and hyperinsulinemia. To study the potential functional adaptations of the islet of Langerhans to in vivo glucocorticoid treatment, adult Wistar rats received dexamethasone (DEX) for 5 consecutive days, whereas controls (CTL) received only saline. The analysis of insulin release in freshly isolated islets showed an enhanced secretion in response to glucose in DEX-treated rats. The study of Ca2+ signals by fluorescence microscopy also demonstrated a higher response to glucose in islets from DEX-treated animals. However, no differences in Ca2+ signals were found between both groups with tolbutamide or KCl, indicating that the alterations were probably related to metabolism. Thus, mitochondrial function was explored by monitoring oxidation of nicotinamide dinucleotide phosphate autofluorescence and mitochondrial membrane potential. Both parameters revealed a higher response to glucose in islets from DEX-treated rats. The mRNA and protein content of glucose transporter-2, glucokinase, and pyruvate kinase was similar in both groups, indicating that changes in these proteins were probably not involved in the increased mitochondrial function. Additionally, we explored the status of Ca2+-dependent signaling kinases. Unlike calmodulin kinase II, we found an augmented phosphorylation level of protein kinase Cα as well as an increased response of the phospholipase C/inositol 1,4,5-triphosphate pathway in DEX-treated rats. Finally, an increased number of docked secretory granules were observed in the β-cells of DEX animals using transmission electron microscopy. Thus, these results demonstrate that islets from glucocorticoid-treated rats develop several adaptations that lead to an enhanced stimulus-secretion coupling and secretory capacity.
Carbohydrate-Responsive Gene Expression in the Adipose Tissue of Rats
Authors: Shankar Kartik , Harrell Amanda , Kang Ping , Singhal Rohit , Ronis Martin J. J. , Badger Thomas M. 
Published: October 2009

AbstractAlthough obesity is often associated with high-fat diets, it can develop from a variety of meal patterns. Excessive intake of simple carbohydrates is one consistent eating behavior leading to obesity. However, the impact of overconsumption of diets with high carbohydrate to fat ratios (C/F) on body composition and global adipose tissue gene expression remains unclear. We used total enteral nutrition to evaluate the effects of caloric intake and C/F on body weight gain and development of obesity. Female Sprague Dawley rats were fed diets with either low C/F or high C/F (HC) (reflecting a 19.5-fold increase in C/F) at two levels of caloric intake: 187 or 220 kcal/kg3/4 · d (15% excess) for 4 wk. At the end of the study period, rats fed HC diets had about 20% higher body weight at either caloric intake compared with rats fed low C/F diets (P &lt; 0.05). Body composition (assessed by nuclear magnetic resonance, computerized tomography, and adipose tissue weights) revealed higher percent fat mass (P &lt; 0.05) in HC rats. Obesity was associated with increased serum resistin, leptin, fasting hyperinsulinemia, and insulin resistance after an oral glucose challenge (P &lt; 0.05). Microarray analyses of adipose tissues revealed HC diets led to changes in 270 and 464 transcripts at 187 and 220 kcal/kg3/4 · d intakes. Genes regulating glucose transport, glycolysis, fatty acid and triglyceride biosynthesis, desaturation and elongation, adipogenesis, and adipokines were affected by HC diets. These results suggest that C/F and interactions with excessive caloric intake per se may regulate body composition and play important roles in the development of obesity and metabolic syndrome.
Selective soft-tissue release for recurrent or residual deformity after conservative treatment of idiopathic clubfoot
Authors: Park S.-S. , Kim S. W. , Jung B.-S. , Lee H. S. , Kim J. S. 
Published: October 2009

We reviewed the results of a selective à la carte soft-tissue release operation for recurrent or residual deformity after initial conservative treatment for idiopathic clubfoot by the Ponseti method. Recurrent or residual deformity occurred in 13 (19 feet) of 33 patients (48 feet; 40%). The mean age at surgery was 2.3 years (1.3 to 4) and the mean follow-up was 3.6 years (2 to 5.3). The mean Pirani score had improved from 2.8 to 1.1 points, and the clinical and radiological results were satisfactory in all patients. However, six of the 13 patients (9 of 19 feet) had required further surgery in the form of tibial derotation osteotomy, split anterior tibialis tendon transfer, split posterior tibialis transfer or a combination of these for recurrent deformity. We concluded that selective soft-tissue release can provide satisfactory early results after failure of initial treatment of clubfoot by the Ponseti method, but long-term follow-up to skeletal maturity will be necessary.
Ten-year follow-up of the non-porous Allofit cementless acetabular component
Authors: Zenz P. , Stiehl J. B. , Knechtel H. , Titzer-Hochmaier G. , Schwagerl W. 
Published: October 2009

Cementless acetabular fixation has demonstrated superior long-term durability in total hip replacement, but most series have studied implants with porous metal surfaces. We retrospectively evaluated the results of 100 consecutive patients undergoing total hip replacement where a non-porous Allofit component was used for primary press-fit fixation. This implant is titanium alloy, grit-blasted, with a macrostructure of forged teeth and has a biradial shape. A total of 81 patients (82 hips) were evaluated at final follow-up at a mean of 10.1 years (8.9 to 11.9). The Harris Hip Score improved from a mean 53 points (23 to 73) pre-operatively to a mean of 96 points (78 to 100) at final review. The osseointegration of all acetabular components was radiologically evaluated with no evidence of loosening. The survival rate with revision of the component as the endpoint was 97.5% (95% confidence interval 94 to 100) after 11.9 years. Radiolucency was found in one DeLee-Charnley zone in four acetabular components. None of the implants required revision for aseptic loosening. Two patients were treated for infection, one requiring a two-stage revision of the implant. One femoral stem was revised for osteolysis due to the production of metal wear debris, but the acetabular shell did not require revision. This study demonstrates that a non-porous titanium acetabular component with adjunct surface fixation offers an alternative to standard porous-coated implants.
Neurological deficit after surgical enucleation of schwannomas of the upper limb
Authors: Park M. J. , Seo K. N. , Kang H. J. 
Published: October 2009

We evaluated 56 patients for neurological deficit after enucleation of a histopathologically confirmed schwannoma of the upper limb. Immediately after the operation, 41 patients (73.2%) had developed a new neurological deficit: ten of these had a major deficit such as severe motor or sensory loss, or intolerable neuropathic pain. The mean tumour size had been significantly larger in patients with a major neurological deficit than in those with a minor or no deficit. After a mean 25.4 months (12 to 85), 39 patients (70%) had no residual neurological deficit, and the other 17 (30%) had only hypoaesthesia, paraesthesiae or mild motor weakness. This study suggests that a schwannoma in the upper limb can be removed with an acceptable risk of injury to the nerve, although a transient neurological deficit occurs regularly after the operation. Biopsy is not advised. Patients should be informed pre-operatively about the possibility of damage to the nerve: meticulous dissection is required to minimise this.
Introduction
Authors: Fuss Eric , Trips Carola 
Published: November 2009

Abstract
This volume is concerned with questions raised by two apparently conflicting observations on the inventory of expressions (and in particular, lexical items) in natural languages. On the one hand, it is widely assumed that the rules of grammar include so-called blocking constraints, which prohibit the co-existence of forms that are identical in meaning, but differ in form. On the other hand, it can be shown that many natural languages exhibit examples of non-blocking and at least some degree of linguistic variation involving exactly this type of (morphological) doublets which can be said to compete for realizing one and the same meaning. In the following we are going to introduce the different types of blocking that are discussed in the literature as well as non-blocking effects to set the contributions in this volume in their context.
A phase-based approach to Scandinavian definiteness marking
Authors: Heck Fabian , Müller Gereon , Trommer Jochen 
Published: November 2009

Abstract
We propose a syntactic approach to apparent blocking effects in the realization of definiteness marking in the Scandinavian languages. The claim is that the differences in definiteness marking can be attributed to a requirement that a definiteness feature ([DEF], a property of N) must be located at the left edge of the DP phase in order to be PIC-accessible for probes outside of the DP. As a result, [DEF] can be spelled out on N if N is the only element within DP and [DEF] is therefore part of DP’s edge domain (giving rise to suffixal marking). In contrast, the presence of an (overt) adjectival modifier (at the left edge of DP) requires feature movement of [DEF] to D, which is then realized as a prenominal article (with additional spell-out of the lower copy of [DEF] in Swedish). The paper also addresses the (slightly different) behavior of definiteness marking in the context of relative clauses and certain issues pertaining to the interpretation of the different strategies.
(Non-)Blocking in the voice system
Authors: Kallulli Dalina 
Published: November 2009

Abstract
This paper deals with (non-) blocking phenomena arising in the context of morphological voice marking patterns, such as active versus passive (as in e.g. Latin), or active versus non-active (as in e.g. Albanian and Modern Greek). Starting from the observation that across languages with voice (or voice-related) marking non-blocking effects arise only with unaccusatives (specifically, with so-called “alternating unaccusatives”), but not for instance with passives or reflexives, the paper presents a variety of facts that converge in showing that this situation is due to a difference in the respective featural make-up of passives and unaccusatives. The central claim that is defended is that the passive morphology is being reanalysed as a morpheme that relates not just to an [–external argument] feature, but to a [+activity] feature (in the sense of Kallulli 2007) in a predicate structure (here: v
0) also containing a [–external argument] feature.
Cytotoxic T lymphocyte antigen-4 Ala17 polymorphism is a genetic marker of autoimmune adrenal insufficiency: Italian association study and meta-analysis of European studies
Authors: Brozzetti Annalisa , Marzotti Stefania , Tortoioli Cristina , Bini Vittorio , Giordano Roberta , Dotta Francesco , Betterle Corrado , De Bellis Annamaria , Arnaldi Giorgio , Toscano Vincenzo , Arvat Emanuela , Bellastella Antonio , Mantero Franco , Falorni Alberto 
Published: November 2009

ObjectiveCytotoxic T lymphocyte antigen-4 (CTLA4) gene polymorphism has been associated with human autoimmune diseases, but discordant data are available on its association with autoimmune Addison's disease (AAD). We tested the human leukocyte antigen (HLA)-independent association of CTLA4+49 (A/G) (Ala 17) and/or CTLA4 CT60 (A/G) polymorphism with AAD.DesignDNA samples from 180 AAD patients and 394 healthy control subjects from continental Italy were analyzed, and association statistical analyses and meta-analysis of published studies were performed.MethodsTaqMan minor groove binder chemistry assays and PCR fragment length polymorphism assays were used.ResultsFrequency of allele G of CTLA4+49 was significantly increased among AAD patients (40% alleles) than among healthy controls (27% alleles; P<0.0001). CTLA4 CT60 polymorphism was associated with AAD only in the heterozygous A/G individuals. The frequency of +49 AG+GG genotypes was significantly higher among AAD patients than among healthy control subjects, in both a co-dominant (P<0.0001) and G dominant model (P<0.0001). CTLA4+49 allele G was significantly associated with disease risk in both patients with isolated AAD and in patients with autoimmune polyendocrine syndrome. Multivariate logistic regression analysis showed that CTLA4+49 allele G was positively associated with AAD (P<0.0001, odds ratio (OR)=2.43, 95% confidence interval=1.54–3.86) also after correction for DRB1*03-DQA1*0501-DQB1*0201, DRB1*04-DQA1*0301-DQB1*0302, and sex. Meta-analysis of five studies revealed a significant association of CTLA4+49 allele G with AAD (P<0.0001) with an overall OR of 1.48 (1.28–1.71).ConclusionsThe CTLA4+49 polymorphism is strongly associated with genetic risk for AAD, independently from the well-known association with HLA class II genes.
Increased suppression of serum ghrelin concentration by hyperinsulinemia in women with anorexia nervosa
Authors: Karczewska-Kupczewska Monika , Strączkowski Marek , Adamska Agnieszka , Nikołajuk Agnieszka , Otziomek Elżbieta , Górska Maria , Kowalska Irina 
Published: November 2009

ContextGhrelin is a peptide secreted mainly by the stomach, which has the ability to stimulate appetite and food intake. Serum ghrelin concentration decreases rapidly after a meal, probably because of the concurrent increase in serum insulin. Anorexia nervosa (AN) is an eating disorder, which is characterized by high serum ghrelin concentration; however, the regulation of circulating ghrelin by insulin in this disorder remains unclear.ObjectiveTo estimate serum ghrelin concentration in the fasting state and after hyperinsulinemia in women with AN.Design and participantsWe examined 19 women with AN, 26 lean healthy women, and 25 women who were overweight or obese. Serum ghrelin concentration was measured in the fasting state and after euglycemic hyperinsulinemic clamp.ResultsInsulin sensitivity was similar in AN and normal-weight women, and was markedly decreased in the obese subjects. In the fasting state, serum ghrelin was higher in AN group than in other groups (normal-weight, P=0.017; obese, P=0.0001) and in normal-weight women than in obese women (P=0.044). Hyperinsulinemia resulted in a marked decrease in serum ghrelin in AN (P<0.0001) and normal-weight women (P=0.002). The fall in serum ghrelin was higher in AN group than in other groups (normal-weight, P=0.0008; obese, P=0.0001), and was related to insulin sensitivity (r=0.24, P<0.05). In multiple regression analysis, only fasting serum ghrelin and the presence of AN were independent predictors of this fall.ConclusionsWomen with AN have an increased suppression of serum ghrelin by hyperinsulinemia. This phenomenon might lead to an increased and more rapid feeling of satiety in AN.