bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer's disease: a cohort study
Authors: Walker Zuzana , McKeith Ian , Rodda Joanne , Qassem Tarik , Tatsch Klaus , Booij Jan , Darcourt Jacques , O'Brien John 
Published: February 2012

ObjectivesDementia with Lewy bodies (DLB) accounts for 10%–15% of dementia cases at autopsy and has distinct clinical features associated with earlier institutionalisation and a higher level of carer distress than are seen in Alzheimer's disease (AD). At present, there is on-going debate as to whether DLB is associated with a more rapid cognitive decline than AD. An understanding of the rate of decline of cognitive and non-cognitive symptoms in DLB may help patients and carers to plan for the future.DesignIn this cohort study, the authors compared 100 AD and 58 DLB subjects at baseline and at 12-month follow-up on cognitive and neuropsychiatric measures.SettingPatients were recruited from 40 European centres.ParticipantsSubjects with mild–moderate dementia. Diagnosis of DLB or AD required agreement between consensus panel clinical diagnosis and visual rating of 123I-FP-CIT (dopamine transporter) single photon emission computed tomography neuroimaging.Outcome measuresThe Cambridge Cognitive Examination including Mini-Mental State Examination and Neuropsychiatric Inventory (NPI).ResultsThe AD and DLB groups did not differ at baseline in terms of age, gender, Clinical Dementia Rating score and use of cholinesterase inhibitors or memantine. NPI and NPI carer distress scores were statistically significantly higher for DLB subjects at baseline and at follow-up, and there were no differences between AD and DLB in cognitive scores at baseline or at follow-up. There was no significant difference in rate of progression of any of the variables analysed.ConclusionsDLB subjects had more neuropsychiatric features at baseline and at follow-up than AD, but the authors did not find any statistically significant difference in rate of progression between the mild–moderate AD and DLB groups on cognitive or neuropsychiatric measures over a 12-month follow-up period.
Treading carefully: a qualitative ethnographic study of the clinical, social and educational uses of exercise ECG in evaluating stable chest pain: Table 1
Authors: Cramer Helen , Evans Maggie , Featherstone Katie , Johnson Rachel , Zaman M Justin S , Timmis Adam D , Hemingway Harry , Feder Gene 
Published: February 2012

ObjectiveTo examine functions of the exercise ECG in the light of the recent National Institute for Health and Clinical Excellence guidelines recommending that it should not be used for the diagnosis or exclusion of stable angina.DesignQualitative ethnographic study based on interviews and observations of clinical practice.Setting3 rapid access chest pain clinics in England.ParticipantsObservation of 89 consultations in chest pain clinics, 18 patient interviews and 12 clinician interviews.Main outcome measureAccounts and observations of consultations in chest pain clinics.ResultsThe exercise ECG was observed to have functions that extended beyond diagnosis. It was used to clarify a patient's story and revise the initial account. The act of walking on the treadmill created an additional opportunity for dialogue between clinician and patient and engagement of the patient in the diagnostic process through precipitation of symptoms and further elaboration of symptoms. The exercise ECG facilitated reassurance in relation to exercise capacity and tolerance, providing a platform for behavioural advice particularly when exercise was promoted by the clinician.ConclusionsMany of the practices that have been built up around the use of the exercise ECG are potentially beneficial to patients and need to be considered in the re-design of services without that test. Through its contribution to the patient's history and to subsequent advice to the patient, the exercise ECG continues to inform the specialist assessment and management of patients with new onset stable chest pain, beyond its now marginalised role in diagnosis.
Incentivising safe sex: a randomised trial of conditional cash transfers for HIV and sexually transmitted infection prevention in rural Tanzania
Authors: de Walque Damien , Dow William H , Nathan Rose , Abdul Ramadhani , Abilahi Faraji , Gong Erick , Isdahl Zachary , Jamison Julian , Jullu Boniphace , Krishnan Suneeta , Majura Albert , Miguel Edward , Moncada Jeanne , Mtenga Sally , Mwanyangala Mathew Alexander , Packel Laura , Schachter Julius , Shirima Kizito , Medlin Carol A 
Published: February 2012

ObjectiveThe authors evaluated the use of conditional cash transfers as an HIV and sexually transmitted infection prevention strategy to incentivise safe sex.DesignAn unblinded, individually randomised and controlled trial.Setting10 villages within the Kilombero/Ulanga districts of the Ifakara Health and Demographic Surveillance System in rural south-west Tanzania.ParticipantsThe authors enrolled 2399 participants, aged 18–30 years, including adult spouses.InterventionsParticipants were randomly assigned to either a control arm (n=1124) or one of two intervention arms: low-value conditional cash transfer (eligible for $10 per testing round, n=660) and high-value conditional cash transfer (eligible for $20 per testing round, n=615). The authors tested participants every 4 months over a 12-month period for the presence of common sexually transmitted infections. In the intervention arms, conditional cash transfer payments were tied to negative sexually transmitted infection test results. Anyone testing positive for a sexually transmitted infection was offered free treatment, and all received counselling.Main outcome measuresThe primary study end point was combined prevalence of the four sexually transmitted infections, which were tested and reported to subjects every 4 months:Chlamydia trachomatis,Neisseria gonorrhoeae,Trichomonas vaginalisandMycoplasma genitalium. The authors also tested for HIV, herpes simplex virus 2 and syphilis at baseline and month 12.ResultsAt the end of the 12-month period, for the combined prevalence of any of the four sexually transmitted infections, which were tested and reported every 4 months (C trachomatis,N gonorrhoeae,T vaginalisandM genitalium), unadjusted RR for the high-value conditional cash transfer arm compared to controls was 0.80 (95% CI 0.54 to 1.06) and the adjusted RR was 0.73 (95% CI 0.47 to 0.99). Unadjusted RR for the high-value conditional cash transfer arm compared to the low-value conditional cash transfer arm was 0.76 (95% CI 0.49 to 1.03) and the adjusted RR was 0.69 (95% CI 0.45 to 0.92). No harm was reported.ConclusionsConditional cash transfers used to incentivise safer sexual practices are a potentially promising new tool in HIV and sexually transmitted infections prevention. Additional larger study would be useful to clarify the effect size, to calibrate the size of the incentive and to determine whether the intervention can be delivered cost effectively.Trial registration numberNCT00922038ClinicalTrials.gov.
Endovascular treatment with ‘kissing’ flow diverter stents of two unruptured aneurysms at a fenestrated vertebrobasilar junction
Authors: Consoli Arturo , Renieri Leonardo , Nappini Sergio , Ricciardi Fabrizio , Grazzini Giulia , Scarpini Giulia , Capaccioli Leonardo , Mangiafico Salvatore 
Published: February 2012

Background and purposeFenestration of the vertebrobasilar junction (VBJ) is a rare condition which may be associated with the presence of aneurysms. The endovascular approach is usually the first-line treatment in these cases since the location of the aneurysm may be unsuitable for a surgical approach. This anatomical variation may even influence the endovascular strategy, particularly in those cases in which the sacrifice of a vessel could be avoided. This paper describes an innovative approach of flow diversion in such challenging situations.MethodsTwo women were admitted after an occasional diagnosis of an aneurysm arising from a fenestrated VBJ. In both cases the endovascular approach was performed with two flow diverter stents and dual antiplatelet therapy was administered for 6 months.ResultsComplete exclusion of the two aneurysms was obtained after 6 and 7 months, respectively, and the clinical outcome was excellent.ConclusionsEndovascular treatment of unruptured aneurysms located on a fenestrated VBJ with flow diverter stents represents a valid therapeutic approach with excellent clinical and radiological outcomes.
Differential WNT Activity in Colorectal Cancer Confers Limited Tumorigenic Potential and Is Regulated by MAPK Signaling
Authors: Horst David , Chen Justina , Morikawa Teppei , Ogino Shuji , Kirchner Thomas , Shivdasani Ramesh A. 
Published: February 2012

AbstractColorectal cancers (CRC) express the WNT effector protein β-catenin in a heterogeneous subcellular pattern rather than uniformly in the nucleus. In this study, we investigated this important aspect of molecular heterogeneity in CRCs by analyzing its basis and relationship with tumor-initiating capability. CRC cells with the highest WNT levels showed only a marginal increase in tumor initiation capacity. Notably, high WNT activity correlated with a coincident activation of robust mitogen-activated protein kinase (MAPK) signaling, which when upregulated by KRAS expression or downregulated by epidermal growth factor receptor inhibition elicited parallel effects on WNT activity. These findings suggested that on its own high WNT activity may not be a reliable signifier of tumor-initiating potential or stem-like potential. Furthermore, they suggest that MAPK signaling is a critical modifier of intratumoral heterogeneity that contributes significantly to determining the impact of WNT activity on stemness phenotypes in colon cancer cells. Cancer Res; 72(6); 1547–56. ©2012 AACR.
Imaging Tumor Sensitivity to a Bioreductive Prodrug: Two for the Price of One!
Authors: Brown J. Martin 
Published: February 2012

Abstract
Hypoxia is an important characteristic of many solid tumors and has a major negative effect on treatment response. A way to combat this effect is with drugs called “bioreductive prodrugs” or “hypoxic cytotoxins,” which are metabolized under hypoxia to toxic species. However, the patients with hypoxic tumors need to be identified. Clin Cancer Res; 18(6); 1487–9. ©2012 AACR.
Two Sides of the Same Coin: EGFR Exon 19 Deletions and Insertions in Lung Cancer
Authors: Politi Katerina , Lynch Thomas J. 
Published: February 2012

Abstract
Most lung adenocarcinoma-associated EGF receptor (EGFR) mutations confer sensitivity to specific EGFR tyrosine kinase inhibitors. The finding that exon 19 insertion mutations are also sensitive to this class of drugs suggests that testing for these mutations should be done and that these patients will benefit from treatment with tyrosine kinase inhibitors. Clin Cancer Res; 18(6); 1490–2. ©2012 AACR.
Honokiol in Combination with Radiation Targets Notch Signaling to Inhibit Colon Cancer Stem Cells
Authors: Ponnurangam Sivapriya , Mammen Joshua M.V. , Ramalingam Satish , He Zhiyun , Zhang Youcheng , Umar Shahid , Subramaniam Dharmalingam , Anant Shrikant 
Published: February 2012

Abstract
Cancer stem cells are implicated in resistance to ionizing radiation (IR) and chemotherapy. Honokiol, a biphenolic compound has been used in traditional Chinese medicine for treating various ailments. In this study, we determined the ability of honokiol to enhance the sensitivity of colon cancer stem cells to IR. The combination of honokiol and IR suppressed proliferation and colony formation while inducing apoptosis of colon cancer cells in culture. There were also reduced numbers and size of spheroids, which was coupled with reduced expression of cancer stem cell marker protein DCLK1. Flow cytometry studies confirmed that the honokiol–IR combination reduced the number of DCLK1+ cells. In addition, there were reduced levels of activated Notch-1, its ligand Jagged-1, and the downstream target gene Hes-1. Furthermore, expression of components of the Notch-1 activating γ-secretase complex, presenilin 1, nicastrin, Pen2, and APH-1 was also suppressed. On the other hand, the honokiol effects were mitigated when the Notch intracellular domain was expressed. To determine the effect of honokiol–IR combination on tumor growth in vivo, nude mice tumor xenografts were administered honokiol intraperitoneally and exposed to IR. The honokiol–IR combination significantly inhibited tumor xenograft growth. In addition, there were reduced levels of DCLK1 and the Notch signaling–related proteins in the xenograft tissues. Together, these data suggest that honokiol is a potent inhibitor of colon cancer growth that targets the stem cells by inhibiting the γ-secretase complex and the Notch signaling pathway. These studies warrant further clinical evaluation for the combination of honokiol and IR for treating colon cancers. Mol Cancer Ther; 11(4); 963–72. ©2012 AACR.
Platelet-mediated proteolytic down regulation of the anticoagulant activity of protein S in individuals with haematological malignancies
Authors: Dienava-Verdoold Ilze , Marchetti Marina R. , te Boome Liane C. J. , Russo Laura , Falanga Anna , Koene Harry R , Mertens Koen , Brinkman Herm Jan M. 
Published: February 2012

SummaryThe natural anticoagulant protein S contains a so-called thrombin-sensitive region (TSR), which is susceptible to proteolytic cleavage. We have previously shown that a platelet-associated protease is able to cleave protein S under physiological plasma conditions in vitro. The aim of the present study was to investigate the relation between platelet-associated protein S cleaving activity and in vivo protein S cleavage, and to evaluate the impact of in vivo protein S cleavage on its anticoagulant activity. Protein S cleavage in healthy subjects and in thrombocytopenic and thrombocythaemic patients was evaluated by immunological techniques. Concentration of cleaved and intact protein S was correlated to levels of activated protein C (APC)-dependent and APC-independent protein S anticoagulant activity. In plasma from healthy volunteers 25% of protein S is cleaved in the TSR. While in plasma there was a clear positive correlation between levels of intact protein S and both APC-dependent and APC-independent protein S anticoagulant activities, these correlations were absent for cleaved protein S. Protein S cleavage was significantly increased in patients with essential thrombocythaemia (ET) and significantly reduced in patients with chemotherapy-induced thrombocytopenia. In ET patients on cytoreductive therapy, both platelet count and protein S cleavage returned to normal values. Accordingly, platelet transfusion restored cleavage of protein S to normal values in patients with chemotherapy-induced thrombocytopenia. In conclusion, proteases from platelets seem to contribute to the presence of cleaved protein S in the circulation and may enhance the coagulation response in vivo by down regulating the anticoagulant activity of protein S.
Urokinase-type plasminogen activator and plasminogen mediate activation of macrophage phagocytosis during liver repair in vivo
Authors: Kawao Naoyuki , Nagai Nobuo , Tamura Yukinori , Horiuchi Yoshitaka , Okumoto Katsumi , Okada Kiyotaka , Suzuki Yasuhiro , Umemura Kazuo , Yano Masato , Ueshima Shigeru , Kaji Hiroshi , Matsuo Osamu 
Published: February 2012

SummaryUrokinase-type plasminogen activator (u-PA) and plasminogen play a primary role in liver repair through the accumulation of macrophages and alteration of their phenotype. However, it is still unclear whether u-PA and plasminogen mediate the activation of macrophage phagocytosis during liver repair. Herein, we investigated the morphological changes in macrophages that accumulated at the edge of damaged tissue induced by a photochemical reaction or hepatic ischaemia-reperfu-sion in mice with u-PA (u-PA−/− ) or plasminogen (Plg−/− ) gene deficiency by using transmission electron and fluorescence microscopy. In wild-type mice, the macrophages aligned at the edge of the damaged tissue and extended a large number of long pseudopodia. These macrophages clearly engulfed cellular debris and showed well-developed organelles, including lysosome-like vacuoles, nuclei, and Golgi complexes. In wild-type mice, the distribution of the Golgi complex in these macrophages was biased towards the direction of the damaged tissue, indicating the extension of their pseudopodia in this direction. Conversely, in u-PA−/− and Plg−/− mice, the macrophages located at the edge of the damaged tissue had few pseudopodia and less developed organelles. The Golgi complex was randomly distributed in these macrophages in u-PA−/− mice. Furthermore, interferon γ and IL-4 were expressed at a low level at the border region of the damaged tissue in u-PA−/− mice. Our data provide novel evidence that u-PA and plasminogen are essential for the phagocytosis of cellular debris by macrophages during liver repair. Furthermore, u-PA plays a critical role in the induction of macrophage polarity by affecting the microenvironment at the edge of damaged tissue.
Hepatocyte growth factor: Molecular biomarker and player in cardioprotection and cardiovascular regeneration
Authors: Madonna Rosalinda , Cevik Cihan , Nasser Maher , De Caterina Raffaele 
Published: February 2012

SummaryThe liver possesses impressive regenerative capacities. Grafts of embryonic liver explants and liver explant-conditioned media have been shown to enhance the mitotic activity of hepatocytes. Hepatocyte growth factor (HGF), also named scatter factor (SF), has been identified as a primary candidate in promoting and regulating liver regeneration. Although initially thought to be a liver-specific mitogen, HGF was later reported to have mitogenic, motogenic, morphogenic, and anti-apoptotic activities in various cell types. By promoting angiogenesis and inhibiting apoptosis, endogenous HGF may play an important role in cardioprotection as well as in the regeneration of endothelial cells and cardiomyocytes after myocardial infarction. Since serum concentration of HGF increases in the early phase of myocardial infarction and in heart failure, HGF may also play a key role as a prognostic and diagnostic biomarker of cardiovascular disease. Here we discuss the role of HGF as a biomarker and mediator in cardioprotection and cardiovascular regeneration.
Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: Resolving uncertainties in routine practice
Authors: Lip Gregory Y. H. , Diener Hans-Christoph , Brueckmann Martina , van Ryn Joanne , Clemens Andreas , Huisman Menno V. 
Published: February 2012

SummaryDabigatran etexilate is a new oral anticoagulant recently approved in Europe for the prevention of stroke or systemic embolism in adult patients with non-valvular atrial fibrillation (AF) and at least one risk factor for stroke. With a fast onset of action and a predictable anticoagulant effect obviating the need for coagulation monitoring, dabigatran etexilate offers practical advantages over vitamin K antagonists in clinical practice. However, clinicians may have questions about practical aspects of dabigatran etexilate use including monitoring anticoagulant efficacy, interruption for surgical or invasive procedures and management of bleeding. This review article aims to address these concerns and provide guidance on the use of dabigatran etexilate in special situations, such as acute coronary syndromes and cardiac revascularisation. In addition, cut-off values for different coagulation assay results associated with an increased risk of bleeding are given.Note: The editorial process for this article was fully handled by Prof. Christian Weber, Editor-in-Chief.
Regulation of microRNA biogenesis and function
Authors: Treiber Thomas , Treiber Nora , Meister Gunter 
Published: February 2012

SummaryMicroRNAs (miRNAs) are considered as key regulators of literally all cellular pathways. Therefore, miRNA biosynthesis and their individual cellular functions must be tightly regulated as well. MiRNAs are transcribed as primary transcripts, which are processed to mature miRNAs in two consecutive maturation steps. Finally, the mature miRNA is incorporated into a miRNA-protein complex, where it directly interacts with a member of the Argonaute (Ago) protein family. The miRNA guides such protein complexes to partial complementary target sites, which are typically located in the 3’ untranslated region (UTR) of mRNAs leading to inhibition of gene expression. MiRNA activity and abundance is regulated on various levels ranging from transcription and processing to target site binding and miRNA stability. Recent advances in our understanding of how miRNA activity is regulated in mammalian cells are summarised and discussed in this review article.
Admission International Normalized Ratio Levels, Early Treatment Strategies, and Major Bleeding Risk Among Non–ST-Segment–Elevation Myocardial Infarction Patients on Home Warfarin Therapy
Authors: Subherwal Sumeet , Peterson Eric D. , Chen Anita Y. , Roe Matthew T. , Washam Jeffrey B. , Gage Brian F. , Bach Richard G. , Bhatt Deepak L. , Wiviott Stephen D. , Lopes Renato D. , Alexander Karen P. , Wang Tracy Y. 
Published: February 2012

Background—
Non–ST-segment–elevation myocardial infarction patients on home warfarin pose treatment concerns because of their potential increased risk of bleeding. Expert opinion from the American College of Cardiology/American Heart Association guidelines suggest holding anticoagulants and initiating antiplatelet therapy among therapeutically anticoagulated non–ST-segment–elevation myocardial infarction patients. Yet, little is known about contemporary treatment patterns and bleeding risks in this population.

Methods and Results—
We stratified 5787 non–ST-segment–elevation myocardial infarction patients on home warfarin therapy using data from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines by admission international normalized ratio (INR) levels: subtherapeutic (INR <2), therapeutic (INR, 2–3), and supratherapeutic (INR >3). Multivariable logistic generalized estimating equations models were constructed to examine the associations between admission INR level, early antithrombotic treatment and invasive therapy, and risk of in-hospital major bleeding. Among these patients, 46%, 35%, and 19% had subtherapeutic, therapeutic, and supratherapeutic admission INR levels, respectively. Risk of major bleeding was higher among patients with therapeutic (15%; adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.03–1.50) and supratherapeutic (22%; odds ratio, 1.60; 95% CI, 1.30–1.97) anticoagulation compared with the subtherapeutic group (12%). Among patients with admission INR ≥2, 45% were treated with early (within 24 hours) heparin, 35% with early clopidogrel, 14% with early glycoprotein IIb/IIIa inhibitor, and 36% with early invasive strategy. Early antithrombotic treatment was associated with increased bleeding risk (odds ratio, 1.40 [95% CI, 1.14–1.72] for heparin; 1.50 [95% CI, 1.22–1.84] for clopidogrel; and 1.82 [95% CI, 1.43–2.32] for glycoprotein IIb/IIIa inhibitor); however, an early invasive strategy was not (odds ratio, 1.09; 95% CI, 0.86–1.37). No significant interactions were observed between INR level and use of each early treatment in its association with bleeding.

Conclusions—
National patterns of early antithrombotic treatment for non–ST-segment–elevation myocardial infarction patients on home warfarin diverge from expert opinion provided by current practice guidelines. Early antithrombotic treatment was associated with increased bleeding risk regardless of admission INR level.