bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTOR in squamous cell carcinoma of the oesophagus: a potential target for molecular therapy?
Authors: Boone J , Kate F J W Ten , Offerhaus G J A , van Diest P J , Rinkes I H M Borel , van Hillegersberg R 
Published: May 2008

Aims:The mammalian target of rapamycin (mTOR), an important regulator of protein translation and cell proliferation, is activated in various malignancies. In a randomised controlled trial of advanced renal cell carcinoma patients, targeted therapy to mTOR by means of rapamycin analogues has been shown to significantly improve survival. An in vitro study has revealed that mTOR is activated in oesophageal squamous cell carcinoma (OSCC) cell lines and that mTOR expression is inhibited by rapamycin. The objectives of this histological study were to determine the proportion of OSCC tissues with activated mTOR (p-mTOR) expression, thereby assessing the percentage of patients with OSCC that would possibly benefit from neoadjuvant rapamycin therapy, and to identify the clinicopathological features of these potentially rapamycin-sensitive tumours.Methods:The expression of p-mTOR (Ser2448) was immunohistochemically assessed in a validated tissue microarray comprising triplicate tissue biopsy cores of 108 formalin-fixed, paraffin-embedded OSCCs. Staining results were correlated with clinicopathological data.Results:Normal oesophageal epithelium was negative for p-mTOR. Activated mTOR expression was located in the cytoplasm of oesophageal tumour cells. 26 (25%) of 105 assessable OSCCs showed tumour cells with positive staining for activated mTOR. Activated mTOR expression was associated with a lesser degree of differentiation only (p = 0.024). No correlation was detected between p-mTOR and the proliferation marker Ki-67.Conclusions:Activated mTOR can be detected in one-quarter of OSCCs. Since this subset of patients may potentially benefit from mTOR inhibiting therapy, a phase II clinical trial of neoadjuvant mTOR-inhibiting therapy in patients with OSCC may be considered.
Integration of conventional cytogenetics, comparative genomic hybridisation and interphase fluorescence in situ hybridisation for the detection of genomic rearrangements in acute leukaemia
Authors: McGrattan P , Campbell S , Cuthbert R , Jones F G C , McMullin M F , Humphreys M 
Published: May 2008

Aims:To screen for genomic imbalances in patients with acute leukaemia using conventional (G-banding) and molecular (comparative genomic hybridisation (CGH) and fluorescence in situ hybridisation (FISH)) methods to determine whether an integrative screening approach increases abnormality detection rate.Methods:G-banded analysis was performed on unstimulated bone marrow (BM) or peripheral blood (PB) cells after short-term (24-hour) culture. CGH was performed on reference (control) and neoplastic (test patient) genomic DNA extracted from BM or PB samples. Interphase FISH (i-FISH) was selectively carried out at disease diagnosis on patients with acute lymphoblastic leukaemia and acute myeloid leukaemia using conventional methods.Results:Genomic rearrangements were detected in 4, 7 and 6 patients using G-banding, CGH and i-FISH respectively. Discordance in results between G-banding, CGH and/or i-FISH was found in 7 of the 12 patients screened. G-banding and CGH, when used individually, detected a genomic imbalance/rearrangement in 33.3% and 58.3%, respectively, of the patients screened. However, when both screening methods were integrated, the abnormality detection rate increased to 66.7%. This detection rate increased further to 75.0% with the use of i-FISH screening.Conclusions:The advantages and disadvantages of using G-banding, CGH and i-FISH as either stand-alone or integrated screening methods for the detection and characterisation of genomic imbalances in acute leukaemia are clearly demonstrated. Abnormality detection rate significantly increased when an integrated screening approach was employed which could potentially provide valuable information for risk stratification in patients with acute leukaemia.
Tobacco use and cessation counselling: cross-country. Data from the Global Health Professions Student Survey (GHPSS), 2005–7
Authors: Warren C W , Jones N R , Chauvin J 
Published: May 2008

Background:Brief intervention by a health professional can substantially increase smoking cessation rates among patients. However, few studies have collected information on tobacco use and training to provide cessation counselling among health professional students.Objective:To examine tobacco use prevalence and tobacco cessation training among students pursuing advanced degrees in health professions.Methods:The Global Health Professions Student Survey (GHPSS) has been conducted among third-year students attending dental, medical, nursing and pharmacy schools. The GHPSS was conducted in schools during regular lectures and class sessions. GHPSS follows an anonymous, self-administered format for data collection.Results:The GHPSS was completed by at least one of the four target disciplines in 31 countries between 2005 and 2007 for a total of 80 survey sites. In 47 of the 80 sites, over 20% of the students currently smoked cigarettes; and in 29 of 77 sites, over 10% of the students currently used other tobacco products. GHPSS data showed that the majority of health professional students recognised that they are role models in society, believed that they should receive training on counselling patients to quit using tobacco, but in 73 of 80 sites less than 40% of the students reported they received such training.Conclusions:Health professional schools, public health organisations and education officials should discourage tobacco use among health professionals and work together to design and implement programmes that train all health professionals in effective cessation counselling techniques. If the goal of the tobacco control community is to reduce substantially the use of tobacco products, then resources should be invested in improving the quality of education of health professionals with respect to tobacco control.
FRACTIONAL MARKET MODEL AND ITS VERIFICATION ON THE WARSAW STOCK EXCHANGE
Authors: KOZŁOWSKA MARZENA , KASPRZAK ANDRZEJ , KUTNER RYSZARD 
Published: May 2008

We analyzed the rising and relaxation of the cusp-like local peaks superposed with oscillations which were well defined by the Warsaw Stock Exchange index WIG in a daily time horizon. We found that the falling paths of all index peaks were described by a generalized exponential function or the Mittag-Leffler (ML) one superposed with various types of oscillations. However, the rising paths (except the first one of WIG which rises exponentially and the most important last one which rises again according to the ML function) can be better described by bullish anti-bubbles or inverted bubbles.2–4 The ML function superposed with oscillations is a solution of the nonhomogeneous fractional relaxation equation which defines here our Fractional Market Model (FMM) of index dynamics which can be also called the Rheological Model of Market. This solution is a generalized analog of an exactly solvable fractional version of the Standard or Zener Solid Model of viscoelastic materials commonly used in modern rheology.5 For example, we found that the falling paths of the index can be considered to be a system in the intermediate state lying between two complex ones, defined by short and long-time limits of the Mittag-Leffler function; these limits are given by the Kohlrausch-Williams-Watts (KWW) law for the initial times, and the power-law or the Nutting law for asymptotic time. Some rising paths (i.e., the bullish anti-bubbles) are a kind of log-periodic oscillations of the market in the bullish state initiated by a crash. The peaks of the index can be viewed as precritical or precrash ones since: (i) the financial market changes its state too early from the bullish to bearish one before it reaches a scaling region (defined by the diverging power-law of return per unit time), and (ii) they are affected by a finite size effect. These features could be a reminiscence of a significant risk aversion of the investors and their finite number, respectively. However, this means that the scaling region (where the relaxations of indexes are described by the KWW law or stretched exponential decay) was not observed. Hence, neither was the power-law of the instantaneous returns per unit time observed. Nevertheless, criticality or crash is in a natural way contained in our FMM and we found its "finger print".
Distribution of von Willebrand factor levels in young women with and without bleeding symptoms. Influence of ABO blood group and promoter haplotypes
Authors: Hillarp Andreas , Ekholm Caroline , Mattson Eva , Halldén Christer , Friberg Britt , Lethagen Stefan 
Published: May 2008

SummaryThe normal distribution of von Willebrand factor (VWF) levels is wide. Low levels are associated with bleeding symptoms and von Willebrand disease (VWD). We have recently described a high prevalence of bleeding symptoms in a whole age group of young females (n = 1,019) from Malmo, Sweden. It was the objective of the present study to evaluate the distribution of VWF levels in young females with or without bleeding symptoms in this population, and the influence of ABO blood group and promoter haplotypes on VWF levels and to identify a possible increased prevalence of VWD in females with bleeding symptoms. A random selection of the female age group (n = 246), into a study group (n = 176) with, and a control group (n = 70) without bleeding symptoms, was evaluated. Eighteen girls had VWF:RCo below the reference range, of which 17 belonged to the study group (17/176, 9.7%), and one to the control group (1/70, 1.4%) (p = 0.017). Blood group O was found in 14/18 girls with low VWF:RCo. There was a highly significant correlation between VWF:RCo and blood group O and non-O genotypes. Two common VWF promoter haplotypes did not contribute to the VWF:RCo variation. VWF levels did not correlate with time during menstrual cycle, or the use of oral contraceptives. No case fulfilled the diagnostic criteria for VWD. In conclusion, low VWF:RCo was significantly more frequent in females with bleeding symptoms. However, we found no case fulfilling strict diagnostic criteria for VWD. The ABO blood group was a strong modifier, but VWF promoter haplotypes had no association to VWF levels in this population.
Fibrinogen Hershey IV: A novel dysfibrinogen with a γV411I mutation in the integrin αIIbβ3 binding site
Authors: Flood Veronica , Al-Mondhiry Hamid , Rein Chantelle , Alexander Kristine , Lovely Rehana , Shackleton Kelley , David Larry , Farrell David 
Published: May 2008

SummaryThe carboxyl terminal segment of the fibrinogen γ chain from γ408–4ll plays a crucial role in platelet aggregation via interactions with the platelet receptor αIIbβ3. We describe here the first naturally-occurring fibrinogen point mutation affecting this region and demonstrate its effects on platelet interactions. DNA sequencing was used to sequence the proband DNA, and platelet aggregation and direct binding assays were used to quantitate the biological effects of fibrinogen Hershey IV. The Hershey IV proband was found to be heterozygous for two mutations, γV411I and γR275C. Little difference in aggregation was seen when fibrinogen Hershey IV was compared to normal fibrinogen. However, less aggregation inhibition was observed using a competing synthetic dodecapeptide containing the V411I mutation as compared to the wild-type dodecapeptide. Purified fibrinogen Hershey IV also bound to purified platelet αIIbβ3 with a lower affinity than wild-type fibrinogen. These findings show that the γV411I mutation results in a decreased ability to bind platelets. In the heterozygous state, however, the available wild-type fibrinogen appears to be sufficient to support normal platelet aggregation.
Simultaneous detection and epitope mapping of anti-factor VIII antibodies
Authors: Lapalud Priscilla , Chtourou Sami , Schved Jean-François , Granier Claude , Lavigne-Lissalde Geraldine , Tarrade Catherine , Villard-Saussine Sylvie 
Published: May 2008

SummaryThe development of antibodies (Abs) against infused factor VIII (FVIII) is currently one of the most serious complications in the treatment of patients suffering from haemophilia A. Improved prevention and eradication of these anti-FVIII Abs remain a challenge for both clinicians and scientists. Here we describe an immunoassay to simultaneously detect and map the epitope specificity of haemophilia A patients’ inhibitors by screening plasma against both heavy and light chains (HC and LC) of human plasma-derived FVIII (pFVIII). The format used was a two-site sandwich assay, where one monoclonal antibody (mAb) specific for the HC or LC was first immobilized on beads, and then incubated with the different forms of pFVIII. After incubation with patients’ plasma samples, binding was revealed by a phycoerythrin-labeled secondary Ab. Samples from haemophilia patients with autoantibodies (autoAb) or alloantibodies (alloAb) were screened in this format. The former preferentially recognized the LC, whereas the latter were directed against both LC and HC. This technology appears attractive as it is fast and requires only 100 μl of patient’s plasma. Furthermore, not only are anti-FVIII Abs detected, but information on their epitopic specificity is also obtained.
Determinants of mean platelet volume (MPV) in an elderly population: Relevance of body fat, blood glucose and ischaemic electrocardiographic changes
Authors: Muscari Antonio , Pascalis Susanna , Ludovico Cosimo , Castaldini Nicola , Antonelli Serafina , Bianchi Giampaolo , Magalotti Donatella , Zoli Marco , Cenni Andrea 
Published: May 2008

SummaryMean platelet volume (MPV) is increased in patients with coronary heart disease or at risk for stroke. However, MPV determinants have never been assessed in a population study. The present investigation is a cross-sectional study involving 366 non-selected subjects (both sexes, mean age 72.9 ± 5.5 [1 SD] years). The main cardiovascular risk factors, several indexes of adiposity (including percent body fat as estimated by skinfold measurement, and ultrasound detection of hepatic steatosis and thickness of abdominal subcutaneous and visceral fat) and ischaemic electrocardiographic (ECG) changes were assessed in all subjects. Platelet parameters were determined by a Bayer ADVIA 120 counter. In addition to being associated directly with platelet distribution width (PDW) and inversely with platelet count (p<0.0001 for both), MPV values were associated with subcutaneous abdominal fat (p=0.02), fasting blood glucose (p=0.002) and the prevalence of ischaemic ECG changes (p=0.004), and tended to be higher in the subjects with a greater prevalence of hepatic steatosis (p=0.07) and higher Homeostasis Model Assessment (HOMA) index (p=0.09). In multiple logistic regression, of the non-platelet parameters only percent body fat (p=0.006), ischaemic ECG changes (p=0.01) and blood glucose (p=0.03) remained independently associated with an MPV ≥8.4 fl (high tertile). The relative risk (odds ratio) of having ischaemic ECG changes for the subjects with MPV ≥8.4 fl was 4.2 (95% confidence interval: 2.5–7.1; p=0.006) with respect to the subjects with lower MPV values. Blood glucose, percent body fat and ischaemic ECG changes were the main MPV determinants in our elderly population.
Efficacy of extended thrombo-prophylaxis in major abdominal surgery: What does the evidence show?
Authors: Elizondo Maria , Doti Carlos , Bruetman Julio , Moreno Pablo , Bullorsky Eduardo , Ceresetto Jose , Bottaro Federico 
Published: May 2008

SummaryVenous thromboembolism (VTE) is a frequent complication following major abdominal surgery. The use of low-molecular-weight heparins (LMWH) to prevent thrombotic events in these patients is a common and well documented practice. However, there is some controversy surrounding the duration of the prophylaxis, as it has been suggested that the risk persists for several weeks after surgery.The objective of this meta-analysis is to systematically review the clinical studies that compared safety and efficacy of extended use of LMWH (for three to four weeks after surgery) versus conventional in-hospital prophylaxis. An electronic data base search was performed. Only randomized, controlled studies were eligible. Data on the incidence of deep vein thrombosis (DVT), VTE and bleeding were extracted. Only three studies fulfilled the inclusion criteria. The indication for surgery was neoplastic disease in 70.6% (780/1104) of patients. The administration of extended LMWH prophylaxis significantly reduced the incidence of VTE, 5.93% (23/388) versus 13.6% (55/405), RR 0.44 (CI 95% 0.28 – 0.7); DVT 5.93% (23/388) versus 12.9% (52/402), RR 0.46 (CI 95% 0,29 – 0,74); proximal DVT 1% (4/388) versus 4.72% (19/402), RR 0.24 (CI 95% 0.09 – 0,67). We found no significant difference in major or minor bleeding between the two groups: 3.85% (21/545) in the extended thrombo-prophylaxis (ETP) group versus 3.48% (19/559) in the conventional prophylaxis group; RR 1.12 (CI 95% 0.61 – 2.06). There was no heterogeneity between the studies. We conclude that ETP with LMWH should be considered as a safe and useful strategy to prevent VTE in high-risk major abdominal surgery.
Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis
Authors: Matsumoto Masanori , Ishizashi Hiromichi , Kato Seiji , Matsuyama Tomomi , Isonishi Ayami , Ishikawa Masatoshi , Yagita Masato , Morioka Chie , Yoshiji Hitoshi , Tsujimoto Tatsuhiro , Kurumatani Norio , Fukui Hiroshi , Uemura Masahito , Fujimura Yoshihiro 
Published: May 2008

SummaryDecreased plasma ADAMTS13 activity (ADAMTS13:AC) results in the accumulation of unusually large von Willebrand factor multimer (UL-VWFM) and the formation of platelet thrombi. It remains controversial whether or not plasma ADAMTS13:AC decreases in patients with liver cirrhosis (LC), and its relationship to clinical features has not been fully investigated. We measured ADAMTS13:AC and its related parameters in plasma in 33 patients with chronic hepatitis (CH) and in 109 patients with LC. ADAMTS13:AC decreased with increasing severity of liver disease (controls means 100%, CH 87%, Child A-LC 79%, Child B-LC 63%, and Child C-LC 31%), and showed severe deficiency (<3% of controls) in five end-stage LC. Activities measured by act-ELISA strongly correlated with those determined by the VWFM assay and ADAMTS13 antigen. Multivariate analysis showed Child-Pugh score and spleen volume independent factors contributing to ADAMTS13:AC. VWFM patterns were normal in 53% of cases, degraded in 31%, and unusually large in 16%. Patients with unusually large VWFM had the lowest ADAMTS13:AC as well as the highest Child-Pugh score, serum creatinine and blood ammonia levels. Plasma inhibitor against ADAMTS13 detected in 83% of patients with severe to moderate ADAMTS13:AC deficiency mostly showed marginal zone between 0.5 and 1.0 BU/ml. The IgG-type autoantibodies specific to plasma derived-ADAMTS13 was detected by Western blot in only five end-stage LC with severe ADAMTS13:AC deficiency. In conclusion, both plasma ADAMTS13 activity and antigen levels decreased with increasing severity of cirrhosis. An imbalance between the decreased ADAMTS13:AC and its increased substrate may reflect the predisposing state for platelet thrombi formation in patients with advanced LC.
Deep vein thrombosis in patients with chronic kidney disease
Authors: Daneschvar H. , Seddighzadeh Ali , Piazza Gregory , Goldhaber Samuel 
Published: May 2008

SummaryDeep vein thrombosis (DVT) is a poorly understood complication of chronic kidney disease (CKD). The objective of our analysis was to profile DVT patients with and without CKD. We defined CKD as patients requiring dialysis or patients having nephrotic syndrome.We compared 268 patients with CKD (184 patients with dialysis-dependent renal disease and 84 with nephrotic syndrome) to 4,307 patients with preserved renal function from a prospective United States multicenter deep venous thrombosis (DVT) registry. Compared with non-CKD patients, CKD patients with DVT were younger (median age 62 vs. 69 years, p<0.0001), more often African- American (p<0.0001), and more often Hispanic (p=0.0003). CKD patients underwent surgery more frequently in the three months prior to developing DVT (48.9% vs. 39.0%, p=0.001) and more often had concomitant congestive heart failure (20.9% vs. 14.6%, p=0.005). CKD patients suffered upper extremity DVT more frequently (30.0% vs. 10.8%, p<0.0001). Patients with CKD presented less often with typical DVT symptoms of extremity discomfort (42.9% vs. 52.4%, p=0.003) and difficulty ambulating (5.4% vs. 10.1%, p=0.01). Prophylaxis rates prior to DVT were similarly low in CKD and non-CKD patients (44.2% vs. 38.0%, p=0.06). Future studies of DVT in CKD patients should explore novel strategies for improving prophylaxis utilization and the detection of DVT in this special population.
Limited diagnostic workup for deep vein thrombosis after major joint surgery
Authors: Peidro Luis , Resines Carlos , Garcés Carlos , Fernández José , Garagorri Eduardo , González Juan , Monreal Manuel ,   for the NETCOT Investigators
Published: May 2008

SummaryWhile deep vein thrombosis (DVT) may be clinically suspected at several time points after major orthopedic surgery, clinical examination is often unreliable, and compression ultrasonography (CUS) screening at discharge is of limited value. A prospective cohort study was carried out in 1,033 consecutive patients who had undergone major hip or knee surgery, aimed to assess the accuracy of a strategy consisting of clinical investigation followed by CUS in the detection of proximal DVT before discharge. The circumferences of both legs were measured in all patients; those exhibiting >2 cm difference between them were considered to have suspected DVT, and underwent bilateral CUS. The same diagnostic workup was repeated on days 45 and 90 after surgery. Three patients developed pulmonary embolism (PE) during admission (one died). Five additional patients died before discharge. Routine clinical evaluation before discharge was done in 1,025 patients, and 105 (10%) had suspected DVT. CUS confirmed the diagnosis in 24 (2.3% of the overall series). After discharge, 59 patients had suspected DVT on day 45, 53 on day 90. DVT diagnosis was confirmed by CUS in 27 (26%).Three additional patients developed PE (1 fatal). This translates into a sensitivity of the routine examinations at discharge of 44%. A limited diagnostic workup for DVT before discharge has the capacity to identify 44% of those patients who will become symptomatic afterwards.
On the Functional Neuroanatomy of Visual Word Processing: Effects of Case and Letter Deviance
Authors: Kronbichler Martin , Klackl Johannes , Richlan Fabio , Schurz Matthias , Staffen Wolfgang , Ladurner Gunther , Wimmer Heinz 
Published: May 2008

Abstract
This functional magnetic resonance imaging study contrasted case-deviant and letter-deviant forms with familiar forms of the same phonological words (e.g., TaXi and Taksi vs. Taxi) and found that both types of deviance led to increased activation in a left occipito-temporal region, corresponding to the visual word form area (VWFA). The sensitivity of the VWFA to both types of deviance may suggest that this region represents well-known visual words not only as sequences of abstract letter identities but also includes information on the typical case-format pattern of visual words. Case-deviant items, in addition, led to increased activation in a right occipito-temporal region and in a left occipital and a left posterior occipito-temporal region, which may reflect increased demands on letter processing posed by the case-deviant forms.