bluuebunny/crossref_metadata_2025_split huggingface dataset:
WNT7A Regulates Tumor Growth and Progression in Ovarian Cancer through the WNT/β-Catenin Pathway
Authors: Yoshioka Shin , King Mandy L. , Ran Sophia , Okuda Hiroshi , MacLean James A. , McAsey Mary E. , Sugino Norihiro , Brard Laurent , Watabe Kounosuke , Hayashi Kanako 
Published: January 2012

Abstract
Abnormal activation the WNT/β-catenin signaling pathway has been associated with ovarian carcinomas, but a specific WNT ligand and pertinent downstream mechanisms are not fully understood. In this study, we found abundant WNT7A in the epithelium of serous ovarian carcinomas, but not detected in borderline and benign tumors, normal ovary, or endometrioid carcinomas. To characterize the role of WNT7A in ovarian tumor growth and progression, nude mice were injected either intraperitoneally or subcutaneously with WNT7A knocked down SKOV3.ip1 and overexpressed SKOV3 cells. In the intraperitoneal group, mice receiving SKOV3.ip1 cells with reduced WNT7A expression developed significantly fewer tumor lesions. Gross and histologic examination revealed greatly reduced invasion of WNT7A knockdown cells into intestinal mesentery and serosa compared with the control cells. Tumor growth was regulated by loss or overexpression of WNT7A in mice receiving subcutaneous injection as well. In vitro analysis of cell function revealed that cell proliferation, adhesion, and invasion were regulated by WNT7A. The activity of the T-cell factor/lymphoid enhancer factor (TCF/LEF) reporter was stimulated by overexpression of WNT7A in ovarian cancer cells. Cotransfection with WNT7A and FZD5 receptor further increased activity, and this effect was inhibited by cotransfection with SFRP2 or dominant negative TCF4. Overexpression of WNT7A stimulated matrix metalloproteinase 7 (MMP7) promoter, and mutation of TCF-binding sites in MMP7 promoter confirmed that activation of MMP7 promoter by WNT7A was mediated by β-catenin/TCF signaling. Collectively, these results suggest that reexpression of WNT7A during malignant transformation of ovarian epithelial cells plays a critical role in ovarian cancer progression mediated by WNT/β-catenin signaling pathway. Mol Cancer Res; 10(3); 469–82. ©2012 AACR.
In Situ Analysis of Mutant EGFRs Prevalent in Glioblastoma Multiforme Reveals Aberrant Dimerization, Activation, and Differential Response to Anti-EGFR Targeted Therapy
Authors: Gajadhar Aaron S. , Bogdanovic Elena , Muñoz Diana Marcela , Guha Abhijit 
Published: January 2012

Abstract
Aberrations in epidermal growth factor receptor (EGFR/ErbB1) are the most common oncogenic alterations in glioblastoma multiforme (GBM), the most common primary brain tumor. Interactions between wild-type (wt) and mutant EGFRs and their subsequent activation are of biologic and potential therapeutic importance in GBMs. We recently showed that in situ proximity ligation assay (PLA) allows for quantitative evaluation of EGFR dimerization and activation in intact cells. Using this in situ platform, we show the aberrant homo-/heterodimeric properties of EGFRvIII and EGFRc958 mutants, the two most common EGFR mutants in GBMs. In addition, dimer phosphoactivation status could be detected by PLA with superior signal–noise ratio (&gt;17-fold) and sensitivity (&gt;16-fold) than immunofluorescence-based phospho-EGFR measurements. Dimer activation analysis indicated quantitative activation differences of mutant dimers. These aberrant features were not overexpression dependent but appeared independent of cellular expression levels, suggesting inherent properties of the mutant receptors. Moreover, we observed in situ detection of EGFRwt-EGFRvIII heterodimerization in GBM specimens, supporting our cell line observations. Notably, currently used anti-EGFR therapeutics, such as cetuximab, matuzumab, and panitumumab, could effectively block EGFRwt dimerization and activation but did not equally impair EGFRvIII homodimers, EGFRwt-EGFRvIII, or EGFRvIII-EGFRc958 heterodimers. EGFRvIII appears to have intrinsic phosphoactivation independent of dimerization as matuzumab blockade of homodimerization had no effect on receptor phosphorylation levels. These data suggest differences in the dimerization-blocking efficacy of EGFR monoclonal antibodies as mutant EGFR dimer configurations prevalent in GBMs can evade blockade by anti-EGFR treatments. Further studies are warranted to evaluate whether this evasion contributes to poor therapeutic response or resistance. Mol Cancer Res; 10(3); 428–40. ©2012 AACR.
Effectiveness of interventions to improve medication adherence in bipolar disorder
Authors: Crowe Marie , Porter Richard , Inder Maree , Lacey Cameron , Carlyle Dave , Wilson Lynere 
Published: January 2012

Objective: To identify interventions that improve medication adherence in bipolar disorder. Method: A review of the literature from 2004 to 2011 was conducted using Medline and manual searching. Results: Eleven studies were identified as meeting inclusion criteria. Five studies demonstrated improved medication adherence. No characteristics of the interventions, clinical characteristics of the groups or methodological factors distinguished those psychosocial interventions that demonstrated improvement from those that did not. Conclusions: While only a few interventions improved adherence, most improved clinical outcomes. Issues were also identified about the way in which adherence is defined. It is proposed that incorporating patient preferences into measures of adherence within the context of a disorder-specific psychosocial intervention may provide an approach that demonstrates both improved adherence and improved clinical outcomes. However this requires further research.
Psychiatrists and termination of pregnancy: Clinical, legal and ethical aspects
Authors: Morris Kirsty , Savell Kristin , Ryan Christopher J 
Published: January 2012

Objective: To provide practical guidance for psychiatrists asked to conduct an assessment of a woman requesting a termination of pregnancy. Method: The law relevant to termination of pregnancy in each of the Australian states and territories and in New Zealand was synthesised and reviewed, as was the available literature around the key roles for the psychiatrist in these settings. Results: Little is known about the rates of and reasons for terminations in Australasia. The ‘lawfulness’ of termination varies between jurisdictions and might require a consideration of the woman’s mental health. When psychiatrists are asked to assist, their roles can be divided into: assessment and management of the woman’s mental health, assessment of the woman’s capacity to consent to the termination, assessment of the impact of having a termination or not having a termination upon the woman’s mental health, assistance in determining the lawfulness of the proposed termination and, finally, support of the obstetric team providing terminations. Conclusions: The psychiatric assessment of a woman requesting a termination of pregnancy requires an understanding of the ethical issues, the relevant law and a clinical framework within which the psychiatrist can delineate his or her various roles.
Private health insurance, mental health and service use in Australia
Authors: Leach Liana S , Butterworth Peter , Whiteford Harvey 
Published: January 2012

Objective: To report on the private health insurance (PHI) status of individuals with and without a mental health problem, and examine whether PHI status is associated with access to psychological services. Methods: This is a descriptive study of nationally representative population-based data collected in 2009 (HILDA) with participants aged 15–93 ( n = 13,301). Key measures included: PHI status (categorised as ‘hospital cover only’, ‘extras cover only’, or ‘both hospital and extras cover’); mental health status (categorised as ‘have a mental health problem’ or ‘do not have a mental health problem’ using the Mental Health Index (MHI) of the Medical Outcomes Study Short Form); mental health service use (access to a mental health professional (psychologist/psychiatrist) in the past 12 months categorised as ‘yes’ or ‘no’). Results: Individuals with a mental health problem were less likely to have PHI than those without a mental health problem. However, PHI was not associated with access to a mental health professional in the past 12 months. Conclusions: The findings suggest that while the discrepancy in PHI status is a marker of inequity between those with and without a mental health problem, it is not a key factor in facilitating access to mental health services.
Over-adjustment or miscomprehension? A re-examination of the jumping to conclusions bias
Authors: Balzan Ryan P , Delfabbro Paul H , Galletly Cherrie A , Woodward Todd S 
Published: January 2012

Objective: Previous research has consistently shown that individuals with delusions typically exhibit a jumping to conclusions (JTC) bias when administered the probabilistic reasoning ‘beads task’ (i.e. decisions made with limited evidence or ‘premature decisions’ and decisions over-adjusted in light of disconfirming evidence or ‘over-adjustment’). More recent work, however, also suggests that these effects may also be influenced by miscomprehension of the task. The current paper is an investigation into the contributing effects of miscomprehension on the JTC bias. Method: A total of 75 participants (25 diagnosed with schizophrenia with a history of delusions; 25 non-clinical delusion-prone; 25 non-delusion-prone controls) completed two identical versions of the beads task, distinct only by the inclusion of an extra instructional set designed to increase comprehension. Results: Qualitative data confirmed that miscomprehension is a valid construct, and the results showed that the addition of an instructional set to the second version of the task led to greater comprehension and a statistically significant drop in ‘over-adjustment’. Nevertheless, both tasks showed that ‘premature decisions’ were significantly more prevalent in the schizophrenia group and were unaffected by the intervention. Conclusions: It was concluded that the ‘premature decisions’ component of the JTC bias remains a feature of decision-making in schizophrenia, but that previously reported ‘over-adjustment’ effects are likely to be influenced by miscomprehension of the beads task instructional set. These findings are discussed in light of the recently proposed ‘hypersalience of evidence-hypothesis matches’ account of the JTC bias.
Risk factors for suicidal ideation in Korean middle-aged adults: The role of socio-demographic status
Authors: Moon Sang-Sik , Park Sang-Mi 
Published: January 2012

Background: The investigations of the risk factors for suicidal ideation among middle-aged adults may be especially important for predicting suicidal actions, given the steep increase in suicide among Koreans aged 45–54. Few studies have sought to investigate the effect of socio-demographic status on suicidal ideation among middle-aged adults. Objective: This study investigated the influence of socio-demographic status on suicidal ideation among middle-aged adults in South Korea. Methods: The sample consisted of middle-aged men ( n = 3,214) and middle-aged women ( n = 4,087) aged 40–64 years who had participated in the 2005 cross-sectional Seoul Citizens Health and Social Indicators Survey. Using multiple logistic regression analysis, we examined the effect of socio-demographic status, health behaviours and health status on suicidal ideation in middle-aged adults. Results: The outstanding finding was that suicidal ideation was most prevalent among middle-aged women who engaged in manual labour (i.e. blue-collar workers) (OR = 2.77, 95% CI = 1.20–6.42). The absence of a spouse was significantly associated with suicidal ideation among middle-aged men (OR = 2.10, 95% CI = 1.30–3.40). Conclusions: The effect of enhanced security related to stable employment was strongest among middle-aged women in blue-collar jobs, and the effect of intensive counselling services was strongest among divorced or widowed middle-aged men.
What psychiatrists should know about sporadic Creutzfeldt-Jakob disease
Authors: Power Brian , Trivedi Darshan , Samuel Mathew 
Published: January 2012

Objective: To provide psychiatrists with relevant, up to date information about sporadic Creutzfeldt-Jakob disease. Conclusions: A 59-year-old bookkeeper presented with psychiatric symptoms in the context of stressors and past history of depression, for which her GP prescribed sertraline and olanzapine. Following a further deterioration in her mental state she was referred to acute psychiatric services, and there found to have dementia and myoclonus, and investigations supported a diagnosis of probable Creutzfeldt-Jakob disease, sporadic type (sCJD). This paper serves to outline the emerging literature challenging the notion that suggests psychiatric symptoms are uncommon in the presentation of sCJD.
The emperor’s edicts stop at the village gate
Authors: O’Connor Nick , Kotze Beth , Vine Ruth , Patton Murray , Newton Richard 
Published: January 2012

Objective: To present an overview of policy implementation, and develop principles for effective policy development and implementation. Method: An overview of literature on policy implementation, and analysis of lessons from some recent experiences in Australian and New Zealand mental health services. Conclusions: Effective development and deployment of policy is much more complex than the commonly held, simplistic compliance model. There are principles that can guide effective policy development and implementation. Future areas of study include the policy implementation systems and change management processes in the health service setting.
Aspirin-insensitive thromboxane biosynthesis in essential thrombocythemia is explained by accelerated renewal of the drug target
Authors: Pascale Silvia , Petrucci Giovanna , Dragani Alfredo , Habib Aida , Zaccardi Francesco , Pagliaccia Francesca , Pocaterra Davide , Ragazzoni Enzo , Rolandi Giancarlo , Rocca Bianca , Patrono Carlo 
Published: January 2012

Abstract
Essential thrombocythemia (ET) is characterized by enhanced platelet generation and thrombotic complications. Once-daily low-dose aspirin incompletely inhibits platelet thromboxane A2 (TXA2) in the majority of ET patients. In the present study, we investigated the determinants of aspirin-insensitive platelet TXA2 biosynthesis and whether it could be further suppressed by changing the aspirin dose, formulation, or dosing interval. In 41 aspirin-treated ET patients, the immature platelet count predicted serum TXB2 independently of platelet count, age, JAK-2 V617F mutation, or cytoreduction (β = 3.53, P = .001). Twenty-one aspirin-treated patients with serum TXB2 ≥ 4 ng/mL at 24 hours after dosing were randomized to the following 7-day regimens in a crossover design: enteric-coated aspirin 100 mg twice daily, enteric-coated aspirin 200 mg once daily, or plain aspirin 100 mg once daily. A twice-daily regimen caused a further 88% median (IQR, 78%-92%, P < .001) TXB2 reduction and normalized the functional platelet response to aspirin, as assessed by urinary 11-dehydro-TXB2 excretion and the VerifyNow Aspirin assay. Doubling the aspirin dose reduced serum TXB2 only partially by 39% median (IQR, 29%-54%, P < .05). We conclude that the abnormal megakaryopoiesis characterizing ET accounts for a shorter-lasting antiplatelet effect of low-dose aspirin through faster renewal of platelet cyclooxygenase-1, and impaired platelet inhibition can be rescued by modulating the aspirin dosing interval rather than the dose.
Regulator of G-protein signaling 18 integrates activating and inhibitory signaling in platelets
Authors: Gegenbauer Kristina , Elia Giuliano , Blanco-Fernandez Alfonso , Smolenski Albert 
Published: January 2012

Abstract
Regulator of G-protein signaling 18 (RGS18) is a GTPase-activating protein for the G-α-q and G-α-i subunits of heterotrimeric G-proteins that turns off signaling by G-protein coupled receptors. RGS18 is highly expressed in platelets. In the present study, we show that the 14-3-3γ protein binds to phosphorylated serines 49 and 218 of RGS18. Platelet activation by thrombin, thromboxane A2, or ADP stimulates the association of 14-3-3 and RGS18, probably by increasing the phosphorylation of serine 49. In contrast, treatment of platelets with prostacyclin and nitric oxide, which trigger inhibitory cyclic nucleotide signaling involving cyclic AMP-dependent protein kinase A (PKA) and cyclic GMP-dependent protein kinase I (PKGI), induces the phosphorylation of serine 216 of RGS18 and the detachment of 14-3-3. Serine 216 phosphorylation is able to block 14-3-3 binding to RGS18 even in the presence of thrombin, thromboxane A2, or ADP. 14-3-3–deficient RGS18 is more active compared with 14-3-3–bound RGS18, leading to a more pronounced inhibition of thrombin-induced release of calcium ions from intracellular stores. Therefore, PKA- and PKGI-mediated detachment of 14-3-3 activates RGS18 to block Gq-dependent calcium signaling. These findings indicate cross-talk between platelet activation and inhibition pathways at the level of RGS18 and Gq.
High-dose clevudine impairs mitochondrial function and glucose-stimulated insulin secretion in INS-1E cells
Authors: Jang Yoon-Ok , Quan Xianglan , Das Ranjan , Xu Shanhua , Chung Choon-Hee , Ahn Chan Mug , Baik Soon-Koo , Kong In Deok , Park Kyu-Sang , Kim Moon Young 
Published: January 2012

AbstractBackgroundClevudine is a nucleoside analog reverse transcriptase inhibitor that exhibits potent antiviral activity against hepatitis B virus (HBV) without serious side effects. However, mitochondrial myopathy has been observed in patients with chronic HBV infection taking clevudine. Moreover, the development of diabetes was recently reported in patients receiving long-term treatment with clevudine. In this study, we investigated the effects of clevudine on mitochondrial function and insulin release in a rat clonal β-cell line, INS-1E.MethodsThe mitochondrial DNA (mtDNA) copy number and the mRNA levels were measured by using quantitative PCR. MTT analysis, ATP/lactate measurements, and insulin assay were performed.ResultsBoth INS-1E cells and HepG2 cells, which originated from human hepatoma, showed dose-dependent decreases in mtDNA copy number and cytochrome c oxidase-1 (Cox-1) mRNA level following culture with clevudine (10 μM-1 mM) for 4 weeks. INS-1E cells treated with clevudine had reduced total mitochondrial activities, lower cytosolic ATP contents, enhanced lactate production, and more lipid accumulation. Insulin release in response to glucose application was markedly decreased in clevudine-treated INS-1E cells, which might be a consequence of mitochondrial dysfunction.ConclusionsOur data suggest that high-dose treatment with clevudine induces mitochondrial defects associated with mtDNA depletion and impairs glucose-stimulated insulin secretion in insulin-releasing cells. These findings partly explain the development of diabetes in patients receiving clevudine who might have a high susceptibility to mitochondrial toxicity.
Klebsiella pneumoniaerelated community-acquired acute lower respiratory infections in Cambodia: Clinical characteristics and treatment
Authors: Rammaert Blandine , Goyet Sophie , Beauté Julien , Hem Sopheak , Te Vantha , Try Patrich Lorn , Mayaud Charles , Borand Laurence , Buchy Philippe , Guillard Bertrand , Vong Sirenda 
Published: January 2012

AbstractBackgroundIn many Asian countries,Klebsiella pneumoniae(KP) is the second pathogen responsible for community-acquired pneumonia. Yet, very little is known aboutKPetiology in ALRI in Cambodia, a country that has one of the weakest medical infrastructures in the region. We present here the first clinico-radiological description ofKPcommunity-acquired ALRI in hospitalized Cambodian patients.MethodsThrough ALRI surveillance in two provincial hospitals,KPwas isolated from sputum and blood cultures, and identified by API20E gallery from patients ≥ 5 years-old with fever and respiratory symptoms onset ≤14 days. Antibiotics susceptibility testing was provided systematically to clinicians when bacteria were isolated. We collected patients' clinical, radiological and microbiological data and their outcome 3 months after discharge. We also comparedKP-related with other bacteria-related ALRI to determine risk factors forKPinfection.ResultsFrom April 2007 to December 2009, 2315 ALRI patients ≥ 5 years-old were enrolled including 587 whose bacterial etiology could be assigned. Of these, 47 (8.0%) hadKPinfection; their median age was 55 years and 68.1% were females. Reported prior medication was high (42.5%). Patients' chest radiographs showed pneumonia (61.3% including 39% that were necrotizing), preexisting parenchyma lesions (29.5%) and pleural effusions alone (4.5%) and normal parenchyma (4.5%). Five patients had severe conditions on admission and one patient died during hospitalization. Of the 39 patients that were hospital discharged, 14 died including 12 within 1 month after discharge. Only 13 patients (28%) received an appropriate antibiotherapy. Extended-spectrum beta-lactamases (ESBL) - producing strains were found in 8 (17.0%) patients. Female gender (Odds ratio (OR) 2.1;p= 0.04) and diabetes mellitus (OR 3.1;p= 0.03) were independent risk factors forKP-related ALRI.ConclusionsKPALRI in Cambodia has high fatality rate, are more frequently found in women, and should be considered in diabetic patients. The extremely high frequency of ESBL-producing strains in the study is alarming in the context of uncontrolled antibiotic consumption and in absence of microbiology capacity in most public-sector hospitals.
Cocaine use during pregnancy assessed by hair analysis in a Canary Islands cohort
Authors: Joya Xavier , Gomez-Culebras Mario , Callejón Alicia , Friguls Bibiana , Puig Carme , Ortigosa Sandra , Morini Luca , Garcia-Algar Oscar , Vall Oriol 
Published: January 2012

AbstractBackgroundDrug use during pregnancy is difficult to ascertain, and maternal reports are likely to be inaccurate. The aim of this study was to estimate the prevalence of illicit drug use among pregnant women by using maternal hair analysis.MethodsA toxicological analysis of hair was used to detect chronic recreational drug use during pregnancy. In 2007, 347 mother-infant dyads were included from the Hospital La Candelaria, Santa Cruz de Tenerife, Canary Islands (Spain). Data on socioeconomic characteristics and on substance misuse during pregnancy were collected using a structured questionnaire. Drugs of abuse: opiates, cocaine, cannabinoids and amphetamines were detected in maternal hair by immunoassay followed by gas chromatography-mass spectrometry for confirmation and quantitation.ResultsHair analysis revealed 2.6% positivity for cocaine and its metabolites. Use of cocaine during pregnancy was associated with unusual behaviour with potentially harmful effects on the baby.ConclusionsThe results of the study demonstrate significant cocaine use by pregnant women in Canary Islands. The data should be used for the purpose of preventive health and policy strategies aimed to detect and possibly to avoid in the future prenatal exposure to drugs of abuse.