bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating antiretinal antibodies predict the outcome of anti‐VEGF therapy in patients with exudative age‐related macular degeneration
Authors: Kubicka‐Trząska Agnieszka , Wilańska Joanna , Romanowska‐Dixon Bożena , Sanak Marek 
Published: August 2011

Abstract.Purpose:  To determine serum antiretinal antibody (ARA) levels in response to treatment with intravitreal bevacizumab of exudative age‐related macular degeneration (AMD).Methods:  The study comprised 22 patients treated with intravitreal bevacizumab (Avastin) 1.25 mg. In all patients, serum ARA levels were assessed by indirect immunofluorescence on normal monkey retina substrate. The ophthalmic examination including best corrected visual acuity (BCVA), fundoscopy, fluorescein angiography, optical coherence tomography (OCT) and immunohistochemical investigations. These were repeated at 4‐week intervals during a loading phase of antiangiogenic therapy. Sera of 22 sex‐ and age‐matched healthy subjects were used as controls for immunohistochemical studies.Results:  Before bevacizumab therapy, ARAs were detected in the sera of all patients at titres ranging from 1:40 to 1:1280. The titres were significantly higher (p < 0.01) than in controls (1:10–1:40). There was no significant correlation between serum ARA titres and neither the type nor the dimensions of choroidal neovascularization, as well as central retinal thickness. Following treatment, all patients demonstrated significant decrease in ARA levels. This correlated with improvement of BCVA, decreased leakage of fluorescein and reduction of subretinal fluid on OCT.Conclusion:  Serum ARA levels demonstrate a dynamic change which occurs in parallel with clinical outcomes of antiangiogenic therapy. They also may act as markers of the therapeutic benefits of vascular endothelial growth factor inhibition.
Dementia in Chinese populations: Current data and future research
Authors: Feng Lei , Chiu Helen , Chong Mian‐Yoon , Yu Xin , Kua Ee‐Heok 
Published: August 2011

AbstractThis review summarizes the literature on the prevalence and incidence rates of dementia in Chinese populations, including survey results outside mainland China. We identified 15 prevalence studies and five incidence studies. The studies consistently reported sharply increased prevalence and incidence rates of dementia with increasing age. As estimated, there are at least 6,464,040 dementia patients in mainland China alone and we expect the number to rise in the coming decades. It is clear that dementia will be a new epidemic of the 21st century without major public health policies and preventive measures that target at the disease. We urge more research and hope that we will be able to prevent dementia or at least delay the onset in the near future with evidence‐based measures.
Surgical management of locoregionally recurrent thymoma
Authors: Park Byungjoon , Park Joon Suk , Kim Hong Kwan , Choi Yong Soo , Kim Kwhanmien , Shim Young Mog , Kim Jhingook 
Published: August 2011

AbstractObjectives:  There is no standard treatment for recurrent thymoma, but treatment is usually palliative therapy. For this article, we retrospectively reviewed our experiences to examine the efficacy of surgical treatment and the extent of adequate resection.Methods:  From 1997 to 2007, 15 patients underwent surgical resection for locoregional recurrence of thymoma in the Samsung Medical Center. The tumors at the initial resection were B1 in two patients, B2 in six, B3 in three and C in four according to the World Health Organization histological classification. Complete resection was achieved in 12 patients with pleurectomy (n = 11) or extrapleural pneumonectomy (n = 1).Results:  There was neither perioperative mortality nor significant immediate postoperative morbidity. After discharge, chest computed tomography scans were evaluated after a minimum of 6 months and the median follow‐up duration was 45 months. At the time of writing, 10 patients had survived with (n = 5) or without (n = 5) rerecurrence (3‐year survival = 84.0%). Survival was significantly superior in patients with complete resection compared with those with incomplete resection (P= 0.008).Conclusions:  Surgical resection could be considered in patients with locoregionally recurrent thymoma because it can be performed safely and offers a chance of long‐term survival to some patients. To achieve complete resection, more extended surgery must be considered for multiple pleural metastases.
Primary biliary cirrhosis – Autoimmune hepatitis overlap syndrome: A rationale for corticosteroids use based on a nation‐wide retrospective study in Japan
Authors: Tanaka Atsushi , Harada Kenichi , Ebinuma Hirotoshi , Komori Atsumasa , Yokokawa Junko , Yoshizawa Kaname , Abe Masanori , Miyake Yasuhiro , Kikuchi Kentaro , Ohira Hiromasa , Zeniya Mikio , Yamamoto Kazuhide , Ishibashi Hiromi , Onji Morikazu , Nakanuma Yasuni , Tsubouchi Hirohito , Takikawa Hajime 
Published: August 2011

Aims:  Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) may simultaneously coexist in some patients, designated as PBC‐AIH overlap syndrome. Previous studies suggest that combination therapy of ursodeoxycholic acid (UDCA) and corticosteroids may be effective. In the current study, we aimed to describe clinical features of these cases and to propose a rationale for combination treatment in PBC‐AIH overlap.Methods:  We enrolled patients with PBC‐AIH overlap from eight referral centers for liver diseases in Japan, and clinical, biochemical and immunological features were examined. Liver histology of all patients at diagnosis were analyzed altogether in detail. Eighty‐nine and 44 patients with PBC and AIH alone were included and served as controls.Results:  We identified 33 patients with PBC‐AIH overlap. The mean follow‐up period was 6.1 years. On liver histology, the HA (hepatitis activity) score was significantly higher than the CA (cholangitis activity) score (P < 0.001). At the end of the follow‐up period, corticosteroids were used in 23 patients (72%), and neither liver‐related death nor liver transplantation had been noted. The sensitivity and specificity of the simplified AIH scoring system for prediction of patients who required corticosteroids during clinical course was 92% and 75% in the training set (n = 17), and 91% and 80% in the validation set (n = 16) of overlap. Only 3% of PBC patients were diagnosed as having indication for corticosteroid use.Conclusion:  In PBC‐AIH overlap, AIH‐like features are dominant in liver histology. The simplified AIH scoring system could predict patients who needed corticosteroids with a higher specificity.
Digging in, Spreading out and Growing up: Introducing CLTS in Africa
Authors: Kar Kamal , Milward Kirsty 
Published: August 2011

SummaryOpen defecation is the norm in rural and urban Africa – only about a third of the population uses improved sanitation facilities – and this contributes in various ways to a heavy disease burden. Community‐led Total Sanitation (CLTS), an approach to sanitation which focuses on community‐wide behaviour change to completely stop open defecation, began to go to scale in Africa in 2006. Since then, it has spread dramatically and in many countries very successfully, and is now used at some level in at least 26 African countries.This paper draws on the extensive involvement of Kamal Kar with the spread of CLTS in Africa to describe the early stages of the process, to elaborate on its developments and to outline insights into the circumstances and features which have facilitated its rapid spread. Taking a broadly comparative approach which draws on the somewhat earlier experience of the spread of CLTS in Asia, it identifies aspects of the institutionalisation process and circumstances, including key individuals, that have contributed to the success of the approach in Africa. It also discusses challenges, however, noting several issues which may limit its impact and hinder its dissemination. In particular, the paper discusses some of the many adaptations made to CLTS in response to a wide range of pressures, varying country circumstances and strategy choices. These adaptations, it is claimed, should be made with a clear picture of what may be lost and gained by adopting them. As CLTS progresses further, it will be important to continue to grapple with these issues, to acknowledge the lessons from adaptations that have had little success, and to retain a vision of the potential of CLTS to bring fundamental transformations in sanitation, health and rural lives.
When can we ignore the problem of imperfect detection in comparative studies?
Authors: Archaux Frédéric , Henry Pierre‐Yves , Gimenez Olivier 
Published: August 2011

Summary1. Numbers of individuals or species are often recorded to test for variations in abundance or richness between treatments, habitat types, ecosystem management types, experimental treatments, time periods, etc. However, a difference in mean detectability among treatments is likely to lead to the erroneous conclusion that mean abundance differs among treatments. No guidelines exist to determine the maximum acceptable difference in detectability.2. In this study, we simulated count data with imperfect detectability for two treatments with identical mean abundance (N) and number of plots (nplots) but different mean detectability (p). We then estimated the risk of erroneously concluding that N differed between treatments because the difference in p was ignored. The magnitude of the risk depended on p, N and nplots.3. Our simulations showed that even small differences in p can dramatically increase this risk. A detectability difference as small as 4–8% can lead to a 50–90% risk of erroneously concluding that a significant difference in N exists among treatments with identical N = 50 and nplots = 50. Yet, differences in p of this magnitude among treatments or along gradients are commonplace in ecological studies.4. Fortunately, simple methods of accounting for imperfect detectability prove effective at removing detectability difference between treatments.5. Considering the high sensitivity of statistical tests to detectability differences among treatments, we conclude that accounting for detectability by setting up a replicated design, applied to at least part of the design scheme and analysing data with appropriate statistical tools, is always worthwhile when comparing count data (abundance, richness).
Paraneoplastic manifestations of cancer in horses
Authors: Axiak S. , Johnson P. J. 
Published: August 2011

SummaryParaneoplastic manifestations of cancer, probably under‐recognised in equine clinical practice, are often observed before the underlying primary disease is identified. This review provides a summary of paraneoplastic phenomena that have been reported in horses. The inclusion of paraneoplastic explanations in the differential diagnosis of common and challenging clinical problems should lead to earlier diagnosis and greater chance for successful therapeutic outcomes. In some cases, alterations in the clinical severity of paraneoplastic signs can be used as indicators of disease progression or response to treatment.
Why Do Influenza Virus Subtypes Die Out? A Hypothesis
Authors: Palese Peter , Wang Taia T. 
Published: August 2011

ABSTRACT
Novel pandemic influenza viruses enter the human population with some regularity and can cause disease that is severe and widespread. The emergence of novel viruses, historically, has often been coupled with the disappearance of existing seasonal virus strains. Here, we propose that the elimination of seasonal strains during virus pandemics is a process mediated, at the population level, by humoral immunity. Specifically, we suggest that infection with a novel virus strain, in people previously exposed to influenza viruses, can elicit a memory B cell response against conserved hemagglutinin stalk epitopes and/or neuraminidase epitopes. The anti-stalk and/or anti-neuraminidase antibodies then act to diminish the clinical severity of disease caused by novel influenza viruses and to eliminate seasonal virus strains.
TLR9 Agonists Oppositely Modulate DNA Repair Genes in Tumor versus Immune Cells and Enhance Chemotherapy Effects
Authors: Sommariva Michele , De Cecco Loris , De Cesare Michelandrea , Sfondrini Lucia , Ménard Sylvie , Melani Cecilia , Delia Domenico , Zaffaroni Nadia , Pratesi Graziella , Uva Valentina , Tagliabue Elda , Balsari Andrea 
Published: August 2011

Abstract
Synthetic oligodeoxynucleotides expressing CpG motifs (CpG-ODN) are a Toll-like receptor 9 (TLR9) agonist that can enhance the antitumor activity of DNA-damaging chemotherapy and radiation therapy in preclinical mouse models. We hypothesized that the success of these combinations is related to the ability of CpG-ODN to modulate genes involved in DNA repair. We conducted an in silico analysis of genes implicated in DNA repair in data sets obtained from murine colon carcinoma cells in mice injected intratumorally with CpG-ODN and from splenocytes in mice treated intraperitoneally with CpG-ODN. CpG-ODN treatment caused downregulation of DNA repair genes in tumors. Microarray analyses of human IGROV-1 ovarian carcinoma xenografts in mice treated intraperitoneally with CpG-ODN confirmed in silico findings. When combined with the DNA-damaging drug cisplatin, CpG-ODN significantly increased the life span of mice compared with individual treatments. In contrast, CpG-ODN led to an upregulation of genes involved in DNA repair in immune cells. Cisplatin-treated patients with ovarian carcinoma as well as anthracycline-treated patients with breast cancer who are classified as “CpG-like” for the level of expression of CpG-ODN modulated DNA repair genes have a better outcome than patients classified as “CpG-untreated-like,” indicating the relevance of these genes in the tumor cell response to DNA-damaging drugs. Taken together, the findings provide evidence that the tumor microenvironment can sensitize cancer cells to DNA-damaging chemotherapy, thereby expanding the benefits of CpG-ODN therapy beyond induction of a strong immune response. Cancer Res; 71(20); 6382–90. ©2011 AACR.
Antiangiogenic Agent Sunitinib Transiently Increases Tumor Oxygenation and Suppresses Cycling Hypoxia
Authors: Matsumoto Shingo , Batra Sonny , Saito Keita , Yasui Hironobu , Choudhuri Rajani , Gadisetti Chandramouli , Subramanian Sankaran , Devasahayam Nallathamby , Munasinghe Jeeva P. , Mitchell James B. , Krishna Murali C. 
Published: August 2011

Abstract
Structural and functional abnormalities in tumor blood vessels impact the delivery of oxygen and nutrients to solid tumors, resulting in chronic and cycling hypoxia. Although chronically hypoxic regions exhibit treatment resistance, more recently it has been shown that cycling hypoxic regions acquire prosurvival pathways. Angiogenesis inhibitors have been shown to transiently normalize the tumor vasculatures and enhance tumor response to treatments. However, the effect of antiangiogenic therapy on cycling tumor hypoxia remains unknown. Using electron paramagnetic resonance imaging and MRI in tumor-bearing mice, we have examined the vascular renormalization process by longitudinally mapping tumor partial pressure of oxygen (pO2) and microvessel density during treatments with a multi-tyrosine kinase inhibitor sunitinib. Transient improvement in tumor oxygenation was visualized by electron paramagnetic resonance imaging 2 to 4 days following antiangiogenic treatments, accompanied by a 45% decrease in microvessel density. Radiation treatment during this time period of improved oxygenation by antiangiogenic therapy resulted in a synergistic delay in tumor growth. In addition, dynamic oxygen imaging obtained every 3 minutes was conducted to distinguish tumor regions with chronic and cycling hypoxia. Sunitinib treatment suppressed the extent of temporal fluctuations in tumor pO2 during the vascular normalization window, resulting in the decrease of cycling tumor hypoxia. Overall, the findings suggest that longitudinal and noninvasive monitoring of tumor pO2 makes it possible to identify a window of vascular renormalization to maximize the effects of combination therapy with antiangiogenic drugs. Cancer Res; 71(20); 6350–9. ©2011 AACR.
Dose-dependent decrease of platelet activation and tissue factor by omega-3 polyunsaturated fatty acids in patients with advanced chronic heart failure
Authors: Berger Rudolf , Hammer Alexandra , Hutuleac Raisa , Koppensteiner Renate , Kopp Christoph , Steiner Sabine , Moertl Deddo 
Published: August 2011

SummaryChronic heart failure (CHF) is characterised by activation of neuroendocrine and inflammatory pathways, and both are linked to a prothrombotic state. Treatment with omega-3 polyunsaturated fatty acids (n3-PUFA) showed significant benefits including mortality reduction in CHF, but exact mechanisms of action are still unclear. We investigated the effects of n3-PUFA on markers of platelet activation and thrombogenesis in patients with severe CHF. Thirty-six patients with non-ischaemic CHF (LVEF<35%, NYHA class>2) under optimised therapy were randomised to supplementation with 1g/day or 4g/day n3-PUFA, or placebo for 12 weeks. Using whole-blood flow cytometry, monocyteplatelet aggregates characterised by CD14+/CD42b+ co-expression and monocytic tissue factor (TF) were determined. Plasma levels of P-selectin, sCD40L, fibrinogen, prothrombin fragment F1.2, TF and proinflammatory markers (high sensitive[hs] interleukin-6, hsCRP, hsTNFalpha, monocyte chemotactic protein-1) were measured by immunoassay. Supplementation with 1g/day and 4g/day n3-PUFA but not placebo significantly reduced monocyte-platelet aggregates in a dose-dependent manner (p for trend=0.02 across the groups). A dose of 4g/day but not 1g/day n3-PUFA significantly decreased P-selectin (p=0.03). Plasma TF decreased dose-dependently upon n3-PUFA supplementation (p for trend=0.02), paralleled by a significant decrease of TF+-monocytes (p for trend=0.01). The amount of 4g/day n3-PUFA exhibited modest anti-inflammatory effects with a significant reduction of hs interleukin-6 (p<0.01) and a trend-wise reduction of hsTNF-alpha (p=0.09). No changes were seen for sCD40L, fibrinogen, hsCRP and monocyte chemotactic protein-1, while F1.2 was decreased by 4g/day n3-PUFA (P=0.03). In patients with severe non-ischaemic CHF, treatment with n3-PUFA leads to a dose-dependent decrease of platelet activation and TF. Higher dosage exhibits also anti-inflammatory effects.* ClinicalTrials.gov registration number: NCT00149409
A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex® (nabiximols)
Authors: Notcutt W , Langford R , Davies P , Ratcliffe S , Potts R 
Published: August 2011

Background: Open-label studies are not ideal for providing robust evidence for long-term maintenance of efficacy of medicines, especially where medicines provide symptom relief and where long-term use of a placebo may be problematic and not ethical. Objective: To evaluate the maintenance of efficacy of Sativex in subjects who have gained long-term symptomatic relief of spasticity in multiple sclerosis (MS), and to assess the impact of sudden medicine withdrawal. Methods: An enriched enrolment randomized withdrawal study design was used. Eligible subjects with ongoing benefit from Sativex for at least 12 weeks entered this 5-week placebo-controlled, parallel-group, randomized withdrawal study. Each subjects’ previous effective and tolerated dose was continued. Results: A total of 18 subjects per group were enrolled. Demographics showed a mean duration of MS of 16.4 years, spasticity 12.7 years, mean duration of Sativex use of 3.6 years (median 3.4 years) and a mean daily dose of 8.25 sprays. Primary outcome of time to treatment failure was significantly in favour of Sativex ( p = 0.013). Secondary endpoints showed significant changes in the Carer and Subject’s Global Impression of Change scales in favour of Sativex. Conclusions: Maintenance of Sativex efficacy in long-term symptomatic improvement of spasticity to a group of subjects with MS has been confirmed using this study design.
Improved sleep efficiency after anti-tumor necrosis factor α therapy in rheumatoid arthritis patients
Authors: Taylor-Gjevre Regina M. , Gjevre John A. , Skomro Robert P. , Nair Bindu V. , Lim Hyun J. 
Published: August 2011

Background: Poor sleep health is increasingly recognized as contributing to decreased quality of life, increased morbidity/mortality and heightened pain perception. Our purpose in this study was to observe the effect on sleep parameters, specifically sleep efficiency, in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor alpha (anti-TNF-α) therapy. Methods: This was a prospective observational study of RA patients with hypersomnolence/poor sleep quality as defined by the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Study patients underwent overnight polysomnograms and completed questionnaire instruments assessing sleep prior to starting anti-TNF-α therapy and again after being established on therapy. The questionnaire included the ESS, PSQI, the Berlin instrument for assessment of obstructive sleep apnea (OSA) risk, restless legs syndrome (RLS) diagnostic criteria, and measures of disease activity/impact. Results: A total of 12 RA patients met inclusion criteria, of which 10 initiated anti-TNF-α therapy and underwent repeat polysomnograms and questionnaire studies approximately 2 months later. Polysomnographic criteria for OSA were met by 60% of patients. Following anti-TNF-α therapy initiation, significant improvements were observed by polysomnography (PSG) for sleep efficiency, increasing from 73.9% (SD 13.5) to 85.4% (SD 9.6) ( p = 0.031), and ‘awakening after sleep onset’ time, decreasing from 84.1 minutes (SD 43.2) to 50.7 minutes (SD 36.5) ( p = 0.048). Questionnaire instrument improvements were apparent in pain, fatigue, modified Health Assessment Questionnaire (mHAQ), and Rheumatoid Arthritis Disease Activity Index (RADAI) scores. Conclusions: Improved sleep efficiency and ‘awakening after sleep onset’ time were observed in RA patients treated with anti-TNF-α therapy.
Sox4 cooperates with PU.1 haploinsufficiency in murine myeloid leukemia
Authors: Aue Georg , Du Yang , Cleveland Susan M. , Smith Stephen B. , Davé Utpal P. , Liu Delong , Weniger Marc A. , Metais Jean Yves , Jenkins Nancy A. , Copeland Neal G. , Dunbar Cynthia E. 
Published: August 2011

Abstract
Cooperation of multiple mutations is thought to be required for cancer development. In previous studies, murine myeloid leukemias induced by transducing wild-type bone marrow progenitors with a SRY sex determining region Y-box 4 (Sox4)–expressing retrovirus frequently carried proviral insertions at Sfpi1, decreasing its mRNA levels, suggesting that reduced Sfpi1 expression cooperates with Sox4 in myeloid leukemia induction. In support of this hypothesis, we show here that mice receiving Sox4 virus-infected Sfpi1ko/+ bone marrow progenitors developed myeloid leukemia with increased penetrance and shortened latency. Interestingly, Sox4 expression further decreased Sfpi1 transcription. Ectopic SOX4 expression reduced endogenous PU.1 mRNA levels in HL60 promyelocytes, and decreased Sfpi1 mRNA levels were also observed in the spleens of leukemic and preleukemic mice receiving Sox4 virus-infected wild-type bone marrow cells. In addition, Sox4 protein bound to a critical upstream regulatory element of Sfpi1 in ChIP assays. Such cooperation probably occurs in de novo human acute myeloid leukemias, as an analysis of 285 acute myeloid leukemia patient samples found a significant negative correlation between SOX4 and PU.1 expression. Our results establish a novel cooperation between Sox4 and reduced Sfpi1 expression in myeloid leukemia development and suggest that SOX4 could be an important new therapeutic target in human acute myeloid leukemia.