bluuebunny/crossref_metadata_2025_split huggingface dataset:
WOMEN, GLASS CEILING, AND PROFESSIONALIZATION IN FAMILY SMEs: A MISSED LINK
Authors: SONGINI LUCREZIA , GNAN LUCA 
Published: January 2010

Literature and practical evidence on the glass ceiling have showed that women's presence in ownership does not ensure that they can significantly influence firm decisional processes. Similarly women's presence in governance roles does not entail glass ceiling removal, even in family firms, which are expected to be a more favorable context. Moreover, literature on women's role in family firms has focused mostly on women's expectations, values, and objectives, on the decision-making processes led by women, on their leadership styles and so on. Very few studies have dealt with women's contribution in strategy formulation, organizational structure design, implementing and using managerial mechanisms. This article focuses on two main topics: the role of women in family firms and the professionalization of the company. It aims at understanding both women's involvement in governance and managerial roles, and the relationship with the family firms' professionalization. The findings reveal, on one hand, that family SMEs are a more favorable context for the removal of the glass ceiling only with regard to the roles of member of board of directors and functional director. On the other hand, they show that some managerial mechanisms, such as incentives and managerial reporting systems, are more relevant when women are involved in governance and managerial roles.
Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method
Authors: Chou Ting-Chao 
Published: January 2010

AbstractThis brief perspective article focuses on the most common errors and pitfalls, as well as the do's and don'ts in drug combination studies, in terms of experimental design, data acquisition, data interpretation, and computerized simulation. The Chou-Talalay method for drug combination is based on the median-effect equation, derived from the mass-action law principle, which is the unified theory that provides the common link between single entity and multiple entities, and first order and higher order dynamics. This general equation encompasses the Michaelis-Menten, Hill, Henderson-Hasselbalch, and Scatchard equations in biochemistry and biophysics. The resulting combination index (CI) theorem of Chou-Talalay offers quantitative definition for additive effect (CI = 1), synergism (CI &lt; 1), and antagonism (CI &gt; 1) in drug combinations. This theory also provides algorithms for automated computer simulation for synergism and/or antagonism at any effect and dose level, as shown in the CI plot and isobologram, respectively. Cancer Res; 70(2); 440–6
E2F8 Contributes to Human Hepatocellular Carcinoma via Regulating Cell Proliferation
Authors: Deng Qing , Wang Qun , Zong Wei-Ying , Zheng Da-Li , Wen Yi-Xin , Wang Ke-Sheng , Teng Xiao-Mei , Zhang Xin , Huang Jian , Han Ze-Guang 
Published: January 2010

Abstract
The E2F family member of transcription factors includes the atypical member E2F8, which has been little studied in cancer. We report that E2F8 is strongly upregulated in human hepatocellular carcinoma (HCC), where it was evidenced to contribute to oncogenesis and progression. Ectopic overexpression of E2F8 promoted cell proliferation, colony formation, and tumorigenicity, whereas E2F8 knockdown inhibited these phenotypes, as documented in Huh-7, Focus, Hep3B, and YY-8103 HCC cell lines. Mechanistic analyses indicated that E2F8 could bind to regulatory elements of cyclin D1, regulating its transcription and promoting accumulation of S-phase cells. Together, our findings suggest that E2F8 contributes to the oncogenic potential of HCC and may constitute a potential therapeutic target in this disease. Cancer Res; 70(2); 782–91
Cell-Free Nucleic Acids Circulating in the Plasma of Colorectal Cancer Patients Induce the Oncogenic Transformation of Susceptible Cultured Cells
Authors: García-Olmo Dolores C. , Domínguez Carolina , García-Arranz Mariano , Anker Phillipe , Stroun Maurice , García-Verdugo José M. , García-Olmo Damián 
Published: January 2010

Abstract
It has been proposed that cell-free nucleic acids in the plasma participate in tumorigenesis and the development of metastases via transfection-like uptake of such nucleic acids by susceptible cells. This putative phenomenon is tentatively referred to as “genometastasis.” In the present study, we examined the effects on cultured cells of plasma from healthy individuals and from patients with colon cancer. Cultures of NIH-3T3 cells and human adipose-derived stem cells (hASC) were supplemented with samples of plasma from patients with K-ras–mutated colorectal tumors or from healthy subjects using two different protocols: direct addition of plasma to cultures in standard plates and addition in the absence of contact between plasma and cells, which were separated by a membrane with 0.4-μm pores. In plasma-treated hASCs, no K-ras–mutated sequences were detected by real-time PCR. In contrast, in most cultures of plasma-treated NIH-3T3 cells (murine cells), the transfer of human DNA occurred, as verified by the detection of human K-ras sequences, p53 sequences, and β-globin–encoding sequences. Moreover, NIH-3T3 cells that had been cultured with plasma from patients with colon cancer were oncogenically transformed, as shown by the development of carcinomas in nonobese diabetic–severe combined immunodeficient mice after the injection of such cells. Microscopic analysis of membranes that had separated plasma from cultured cells confirmed the complete absence of cells in the plasma. We only observed noncell particles, having diameters of &lt;0.4 μm. Our results indicate that plasma from cancer patients is able to transform cultured cells oncogenically, supporting the previously proposed hypothesis of genometastasis. Cancer Res; 70(2); 560–7
Time to Treatment Response in Patients with Follicular Lymphoma Treated with Bortezomib Is Longer Compared with Other Histologic Subtypes
Authors: O'Connor Owen A. , Portlock Carol , Moskowitz Craig , Hamlin Paul , Straus David , Gerecitano John , Gonen Mithat , Dumitrescu Otilia , Sarasohn Debra , Butos John , Neylon Ellen , Mac-Gregor Cortelli Barbara , Blumel Susan , Evens Andrew M. , Zelenetz Andrew D. , Wright John , Cooper Brenda , Winter Jane , Vose Julie 
Published: January 2010

Abstract
Purpose: To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent non–Hodgkin's lymphoma.
Experimental Design: Patients with follicular lymphoma (FL), marginal zone lymphoma, mantle cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia were eligible for study. Bortezomib was given at a dose of 1.5 mg/m2 as an i.v. push on days 1, 4, 8, and 11 of a 21-day cycle. Eligibility included the following: (a) no more than three prior therapies, (b) at least 1 month since prior chemotherapy, (c) measurable disease, and (d) an absolute neutrophil count of &gt;1,000/μL and a platelet count &gt;50,000/μL for the first dose of any cycle.
Results: Seventy-seven patients were registered, of which 69 were assessable for response based on the completion of two cycles of therapy. Subtypes included FL (59.5%), mantle cell lymphoma (52%), small lymphocytic lymphoma/chronic lymphocytic leukemia (16.2%), marginal zone lymphoma (21.6%), and one Waldenstrom's macroglobulinemia. The median number of prior therapies was three. The most common grade 3 toxicity was lymphopenia (35%) and thrombocytopenia (31%). Twenty-five patients experienced grade ≤2 sensory neuropathy (32), and 8% experienced grade 3 neurosensory toxicity. The overall response rate was 45% (40% on an intention to treat) including 10 complete remissions. Of 18 patients with FL, 9 responded with 4 complete response. The median time to treatment response for FL was 12 weeks, whereas the median time to treatment response for other subtypes of non–Hodgkin's lymphoma was only 4 weeks.
Conclusions: These data suggest that bortezomib has significant single agent activity in patients with FL, and that longer durations of treatment may improve overall response. Clin Cancer Res; 16(2); 719–26
GSK690693 Delays Tumor Onset and Progression in Genetically Defined Mouse Models Expressing Activated Akt
Authors: Altomare Deborah A. , Zhang Lili , Deng Jing , Di Cristofano Antonio , Klein-Szanto Andres J. , Kumar Rakesh , Testa Joseph R. 
Published: January 2010

Abstract
Purpose: Akt plays a central role in regulating tumor cell survival and cell cycle progression and is regarded as a promising therapeutic target. We used genetically defined mouse models that develop spontaneous tumors exhibiting activated Akt to determine if Akt inhibition by GSK690693 is effective in the treatment of cancer. The broad long-term objective of this project was to use preclinical cancer models with precisely defined genetic lesions to elucidate the efficacy of targeting Akt with GSK690693.
Experimental Design: We tested the in vivo effects of GSK690693 in Lck-MyrAkt2 transgenic mice that develop lymphomas, heterozygous Pten+/− knockout mice that exhibit endometrial tumors, and TgMISIIR-TAg-DR26 mice that develop ovarian carcinomas, all of which exhibit hyperactivation of Akt. In addition to standard disease onset and histology, tumors arising in treated animals were examined by immunohistochemistry to verify downregulated Akt signaling relative to placebo-treated mice. When possible, drug response was evaluated in tumor cell cultures by standard proliferation and apoptosis assays and by immunoblotting with various phosphospecific antibodies.
Results: GSK690693 exhibited efficacy irrespective of the mechanism of Akt activation involved. Interestingly, GSK690693 was most effective in delaying tumor progression in Lck-MyrAkt2 mice expressing a membrane-bound, constitutively active form of Akt. Both tumors and primary cell cultures displayed downregulation of the Akt pathway, increased apoptosis, and primarily decreased cell proliferation.
Conclusion: These results suggest that GSK690693 or other Akt inhibitors might have therapeutic efficacy in human cancers with hyperactivated Akt and/or a dependence on Akt signaling for tumor progression. Clin Cancer Res; 16(2); 486–96
Mechanisms of Inactivation of PTCH1 Gene in Nevoid Basal Cell Carcinoma Syndrome: Modification of the Two-Hit Hypothesis
Authors: Pan Shuang , Dong Qing , Sun Li-Sha , Li Tie-Jun 
Published: January 2010

Abstract
Purpose: PTCH1 has been identified as the gene responsible for nevoid basal cell carcinoma syndrome (NBCCS). Keratocystic odontogenic tumors (KCOT) are aggressive jaw lesions that may occur in isolation or in association with NBCCS. The aim of this study was to investigate the genetic and/or epigenetic mechanisms of inactivation of the PTCH1 gene in patients with NBCCS and related sporadic KCOTs.
Experimental Design: Loss of heterozygosity was analyzed in 44 patients (15 NBCCS-related and 29 sporadic KCOTs), all of whom were previously analyzed for PTCH1 mutations. Allelic location was established in tumors carrying two coincident mutations. PTCH1 mRNA expression and promoter methylation status were analyzed in a panel of KCOTs to define the possible role of epigenetic effects on PTCH1 inactivation.
Results: Although mutations and loss of heterozygosity of PTCH1 were frequently detected in both syndromic and nonsyndromic cases, hypermethylation of the PTCH1 promoter was not identified in the present series. Of all the 44 cases examined, 13 were identified to fit the two-hit model, 14 to conform to a one-hit model, and the remaining 17 cases showing no alteration in PTCH1. The distribution of two-hit, one-hit, and non-hit cases was significantly different between syndrome and nonsyndrome patients (P &lt; 0.02).
Conclusions: This study indicates that PTCH1 gene alternation may play a significant role in the pathogenesis of NBCCS and the related sporadic tumors. Not only the standard two-hit model, but also haploinsufficiency or dominant-negative isoforms may be implicated in the inactivation of the PTCH1 gene. Clin Cancer Res; 16(2); 442–50
Individualizing Dosing of Irinotecan
Authors: Ratain Mark J. , Innocenti Federico 
Published: January 2010

AbstractIndividualized drug dosing is a longstanding goal of clinical pharmacologists. Given the narrow therapeutic index of most anticancer agents, it is plausible that this approach would be of particular value in oncology. Irinotecan is an interesting agent for individualized dosing, given its complex metabolism and increasing knowledge of its pharmacokinetics predictors. Clin Cancer Res; 16(2); 371–2
The influence of the menstrual cycle, normal pregnancy and pre-eclampsia on platelet activation
Authors: Robb Amy , Din Jehangir , Mills Nicholas , Smith Imogen , Blomberg Anders , Zikry Mariam , Raftis Jennifer , Newby David , Denison Fiona 
Published: January 2010

SummaryPlatelet activation has a key role in mediating thrombotic and inflammatory events. This study aimed to determine the influence of the menstrual cycle, pregnancy and preeclampsia on in vivo platelet activation. Twelve healthy nulliparous, non-smoking women with regular menses were studied over a single menstrual cycle. Twenty-one healthy primigravida pregnant women were studied longitudinally at 16, 24, 32 and 37 weeks gestation and seven weeks post-partum. Sixteen primigravida women with preeclampsia were studied at time of diagnosis and at seven weeks post-partum. Platelet-monocyte aggregates and platelet-surface P-selectin expression were assessed by flow-cytometry. Soluble P-selectin and CD40 ligand (CD40L) were measured by ELISA. Markers of platelet activation did not vary over the menstrual cycle. Platelet-monocyte aggregates were greater in the third trimester of pregnancy compared to non-pregnant women (p=0.003). Platelet surface and plasma soluble P-selectin concentrations increased with gestation (p<0.0001) and were raised by 24 weeks of pregnancy compared to non-pregnant women (p≤0.02 for both) and together with platelet monocyte aggregates, decreased post-partum (p≤0.02). Soluble CD40L concentrations fell in pregnancy, reaching a nadir at mid-gestation (p=0.002). There were no differences in markers of platelet activation between normal and pre-eclamptic pregnancies. In conclusion, platelet activation is increased in pregnancy and increases with gestation but is unaffected by preeclampsia. This suggests that systemic platelet activation is a feature of pregnancy but this is not affected by established preeclampsia.
Effect of two doses of aspirin on thromboxane biosynthesis and platelet function in patients undergoing coronary surgery
Authors: Brambilla Marta , Parolari Alessandro , Camera Marina , Colli Susanna , Eligini Sonia , Centenaro Chiara , Anselmo Achille , Alamanni Francesco , Tremoli Elena 
Published: January 2010

SummaryEarly post-operative aspirin improves survival in patients undergoing coronary artery bypass graft (CABG). However, most patients do not benefit of aspirin after CABG, still remaining at risk of thrombotic events due to insufficient platelet inhibition, specifically via the thromboxane (TX) pathway. We evaluated the effect of two aspirin doses (100 or 325 mg daily, enteric coated formulations) on platelet function and TX biosynthesis in patients after CABG and assessed whether the incidence of residual platelet reactivity could be reduced by the higher dose. Fifty-six patients undergoing CABG were randomly assigned to 100 or 325 mg aspirin daily for five days in a prospective single-centre study. Treatment effect was assessed by measuring either platelet function (light-transmission aggregometry and point-of-care PFA-100®) or TX biosynthesis in collagen-stimulated platelets, serum, urine, and in lipopolysaccharide (LPS)-cultured whole blood (WB). An insufficient TX inhibition was observed with 100 mg aspirin but not with the higher dose. The different effect of the two doses was, however, highlighted by either TX (platelet- or serum-derived) or by PFA-100® but not by the other assays. In conclusion, early after CABG, the incidence of residual platelet activity was lower in patients who received 325 mg aspirin. Moreover, evidence was provided that different methods yield different results in the detection of aspirin resistance, rendering them not interchangeable.
Safety and tolerability of an immediate-release formulation of the oral direct thrombin inhibitor AZD0837 in the prevention of stroke and systemic embolism in patients with atrial fibrillation
Authors: Rasmussen Lars , Tveit Arnljot , Jensen Eva , Wessman Peter , Panfilov Seva , Wåhlander Karin , Olsson Bertil 
Published: January 2010

SummaryAZD0837 is an investigational oral anticoagulant which is converted to the active form, AR-H067637, a selective direct thrombin inhibitor. The present study, a multicentre, randomised, parallel-group, dose-guiding study, assessed the safety and tolerability of an immediate-release formulation of AZD0837 compared with dose-adjusted warfarin in the prevention of stroke and systemic embolic events in atrial fibrillation (AF) patients. Two hundred fifty AF patients with at least one additional risk factor for stroke were randomised to receive either immediate-release AZD0837 (150 mg twice daily [bid] or 350 mg bid, blinded treatment) or dose-adjusted warfarin (international normalised ratio 2.0–3.0, open treatment) for three months. The safety and tolerability of 150 mg bid AZD0837 appeared to be as good as that of warfarin. Total bleeding events were six with 150 mg bid AZD0837, 15 with 350 mg bid AZD0837 and eight with warfarin. Alanine aminotransferase elevations (> 3 x upper limit of normal) were infrequent, without apparent differences between treatment groups. A numerically higher incidence of serious adverse events was observed with 350 mg bid AZD0837 compared with 150 mg bid, with six of 13 being cardiac related, all with different diagnoses. An increase in mean serum creatinine of approximately 10% was observed in both AZD0837 groups, which returned to baseline after completion of therapy. There were no strokes, transient ischaemic attacks or cerebral haemorrhages with any of the treatments. In conclusion, the safety and tolerability of 150 mg bid immediate-release AZD0837 appeared to be as good as that of dose-adjusted warfarin. However, larger studies will be needed to define the safety profile of AZD0837.
Bone mineral density in haemophilia patients
Authors: Fabbriciani Gianluigi , Marcucci Maura , Brozzetti Matteo , Filipponi Paolo , Iorio Alfonso 
Published: January 2010

SummaryOsteoporosis is caused by bone mineral density (BMD) reduction. Haemophilia patients are at increased risk of osteoporosis because of decreased physical activity and blood-borne virus infections. This systematic review of the literature aims at evaluating BMD reduction in severe haemophilia patients and its correlation with patients’ characteristics. Seven case-control studies evaluating lumbar BMD values [g/cm2] (all studies), BMI (5/7 studies), and hepatitis C virus (HCV) seropositivity (6/7 studies) in severe haemophilia patients and controls were meta-analysed. Standardised mean difference (SMD) of BMD was used to compare cases and controls. The effect of body mass index (BMI) and HCV infection was investigated by meta-regression. One hundred one adult cases (age 33 ± 8.9) with 101 controls and 111 paediatric cases (age 8 ± 3.6) with 307 controls were available for analysis. Lumbar BMD was significantly lower in severe haemophilia patients than in controls, both in adult (pooled SMD –1.379, 95% confidence interval [CI] –2.355 to –0.403, p=0.006) and children (pooled SMD –0.438, 95% CI –0.686 to –0.189, p=0.001). The reduction in BMD in patients versus controls was not significantly correlated with the reduction in BMI or with the percentage of HCV-infected patients. This meta-analysis confirms the association between severe haemophilia and low BMD. Future studies should investigate fracture rates and interventions to prevent bone loss in persons with haemophilia
The Formation of a Communal Identity among West Syrian Christians: Results and Conclusions of the Leiden Project
Authors: van Ginkel Jan , Atto Naures , Snelders Bas , Immerzeel Mat , Romeny Bas ter Haar 
Published: January 2010

AbstractAmong those who opposed the Council of Chalcedon in 451, the West Syrian (or Syriac Orthodox) Christians were probably least likely to form a national or ethnic community. Yet a group emerged with its own distinctive literature and art, its own network, and historical consciousness. In an intricate process of adoption and rejection, the West Syrians selected elements from the cultures to which they were heirs, and from those with which they came into contact, thus defining a position of their own. In order to study this phenomenon, scholars from various disciplines, and affiliated to two different faculties, were brought together in a programme financed by the Netherlands Organization for Scientific Research NWO. This essay introduces their research project and methodology, and presents their results and conclusions.
What Does Recovery From Schizophrenia Mean? Perceptions of Medical Students and Trainee Psychiatrists
Authors: Ng Roger M.K. , Pearson Veronica , Chen Eric E.Y. , Law C.W. 
Published: January 2010

Background: The attitudes of medical professionals towards recovery from schizophrenia are key in defining the therapeutic encounter and may change as they move through their medical career. Method: A qualitative methodology was used based on three focus groups of medical students and trainee psychiatrists in Hong Kong. Both held pessimistic attitudes towards recovery in schizophrenia. Four major categories and one central theme emerged, with little difference between students and doctors. The four categories were: (1) recovery is defined by the cessation of medication and the resumption of normal psychosocial functioning; (2) formal recovery requires medical confirmation plus the patient’s admission of illness; (3) recovery should be discussed, but largely in terms of the contribution of drug compliance; and (4) participants recognized that stigma was an impediment to recovery while holding attitudes that were as unaccepting towards people with schizophrenia as lay people’s. Conclusions: Traditional medical education over-emphasizes symptomatic recovery and ignores the need for a more flexible construction of the concept. Professional knowledge must incorporate both quantitative and qualitative data and inculcate humanitarian concern through active contact with users, and acceptance of the legitimacy of their expert experience. Medical education should seek effective ways to change entrenched negative attitudes in students about schizophrenia and the possibility of recovery. Further large-scale research should be carried out to establish attitudes of medical professionals towards recovery from schizophrenia and how this changes during typical career trajectories. This information could then be used to devise effective means within medical education to combat stigma and change attitudes.
Lifelong Learning for the African to Become a Twenty-First Century Person in the Global System
Authors: Tefe Theophilus 
Published: January 2010

The Dakar Conference on Education organized by UNESCO in 1972 led to the formation of a commission on education chaired by Edgar Faure. In 1996 the commission released what later on became known as Delores’ Report on Education as a framework or philosophy on which member countries of UNESCO could base their education systems. The framework consists of four basic principles: Learning to be, Learning to know, Learning to do and Learning to live together. This article discusses how to learn to become a person from the home, to the school and throughout life (lifelong Learning) in Africa. The focus is on Africa because it is one continent where education does not seem to be making a significant impact, as it is doing in other parts of the world – preparing the people to meet the challenges of the twenty-first century