bluuebunny/crossref_metadata_2025_split huggingface dataset:
8-Amino-Adenosine Activates p53-Independent Cell Death of Metastatic Breast Cancers
Authors: Polotskaia Alla , Hoffman Sandy , Krett Nancy L. , Shanmugam Mala , Rosen Steven T. , Bargonetti Jill 
Published: September 2012

Abstract8-Amino-adenosine (8-NH2-Ado) is a ribose sugar nucleoside analogue that reduces cellular ATP levels and inhibits mRNA synthesis. Estrogen receptor-negative (ER−) metastatic breast cancers often contain mutant p53; therefore, we asked if 8-NH2-Ado could kill breast cancer cells without activating the p53-pathway. Regardless of the breast cancer subtype tested or the p53 status of the cells, 8-NH2-Ado was more cytotoxic than either gemcitabine or etoposide. 8-NH2-Ado treatment inhibited cell proliferation, activated cell death, and did not activate transcription of the p53 target gene p21 or increase protein levels of either p53 or p21. This occurred in the estrogen receptor-positive (ER+) MCF-7 cells that express wild-type p53, the ER+ T47-D cells that express mutant p53, and the ER− MDA-MB-468 cells or MDA-MB-231 cells that both express mutant p53. 8-NH2-Ado induced apoptotic death of MCF-7 cells and apoptosis was not inhibited by knockdown of functional p53. Moreover, the pan-caspase inhibitor Z-VAD blocked the 8-NH2-Ado–induced MCF-7 cell death. Interestingly, 8-NH2-Ado caused the MDA-MB-231 cells to detach from the plate with only limited evidence of apoptotic cell death markers and the cell death was not inhibited by Z-VAD. Inhibition of MDA-MB-231 cell autophagy, by reduction of ATG7 or 3-methyladenine treatment, did not block this 8-NH2-Ado–mediated cytotoxicity. Importantly 8-NH2-Ado was highly cytotoxic to triple-negative breast cancer cells and worked through a pathway that did not require wild-type p53 for cytoxicity. Therefore, 8-NH2-Ado should be considered for the treatment of triple-negative breast cancers that are chemotherapy resistant. Mol Cancer Ther; 11(11); 2495–504. ©2012 AACR.
Gene-Targeted Analysis of Copy Number Variants Identifies 3 Novel Associations With Coronary Heart Disease Traits
Authors: Costelloe Seán J. , El-Sayed Moustafa Julia S. , Drenos Fotios , Palmen Jutta , Qiao Li , Whiting Stephen , Thomas Michael , Kivimaki Mika , Kumari Meena , Hingorani Aroon D. , Tzoulaki Ioanna , Marjo-Riitta Järvelin , Aimo Ruokonen , Hartikainen Anna-Liisa , Pouta Anneli , Walters Robin G. , Blakemore Alexandra I.F. , Humphries Steve E. , Coin Lachlan J. M. , Talmud Philippa J. 
Published: September 2012

Background—
Copy number variants (CNVs) are a major form of genomic variation, which may be implicated in complex disease phenotypes. However, investigation of the role of CNVs in coronary heart disease (CHD) traits has been limited.

Methods and Results—

We examined the use of the cnvHap algorithm for CNV detection, using data for 2500 men from the Second Northwick Park Heart Study (NPHS-II). An Illumina custom chip, including 722 single-nucleotide polymorphisms covering 76 coronary heart disease-trait genes, was used. Common CNVs were significantly associated (at
P
<0.05, after correction) with coronary heart disease phenotypes in 5 genes. Novel associations of CNVs in toll-like receptor-4 with apolipoprotein AI were replicated (
P
<0.05) in the Whitehall II cohort (4887 subjects), whereas newly described associations of CNVs in sterol regulatory element-binding protein with apolipoprotein AI and associations of interleukin-6 signal transducer with apolipoprotein B were replicated in the data from 3546 subjects from the North Finnish Birth Cohort 1966 (
P
<0.05).

Conclusions—
This study supports the use of CNV detection algorithms such as cnvHap as potential tools for the identification of novel CNVs, some of which show significant association and replication with coronary heart disease risk phenotypes. However, the functional basis for these associations requires further substantiation.
Prospective Study of Restless Legs Syndrome and Coronary Heart Disease Among Women
Authors: Li Yanping , Walters Arthur S. , Chiuve Stephanie E. , Rimm Eric B. , Winkelman John W. , Gao Xiang 
Published: September 2012

Background—
Previous cross-sectional studies suggested a positive association between restless legs syndrome (RLS) and coronary heart disease (CHD). This observation was not confirmed by subsequent prospective studies. However, these prospective studies did not take into account the duration of RLS symptoms. Therefore, we prospectively examined whether RLS was associated with an increased risk of CHD in women who participated in the Nurses' Health Study, taking into account the duration of RLS symptoms.

Methods and Results—

A total of 70 977 women (mean age, 67 years) who were free of CHD and stroke at baseline (2002) were followed up until 2008. Physician-diagnosed RLS was collected via questionnaire. CHD was defined as nonfatal myocardial infarction or fatal CHD. Women with RLS at baseline had a marginally higher risk of developing CHD (multivariable-adjusted hazard ratio, 1.46; 95% confidence interval, 0.97–2.18) compared with women without RLS. The risk was dependent on duration of symptoms: 0.98 (95% confidence interval, 0.44–2.19) for women with RLS for <3 years and 1.72 (95% confidence interval, 1.09–2.73) for women with RLS for ≥3 years (
P
trend=0.03). The multivariable-adjusted hazard ratios of women with RLS for ≥3 years were 1.80 (95% confidence interval, 1.07–3.01) for nonfatal myocardial infarction and 1.49 (95% confidence interval, 0.55–4.04) for fatal CHD relative to women without RLS.

Conclusions—
We observed that women with RLS for at least 3 years had an elevated risk of CHD. These results suggest that RLS or RLS-associated conditions may contribute to the origin of cardiovascular disease.
Bad, burdened or ill? Characterizing the spouses of women with schizophrenia
Authors: Seeman Mary V 
Published: September 2012

Background: The husbands of women with schizophrenia have been variously characterized in the psychiatric literature as abusive, burdened and ill. The aim of this paper is to summarize what has been written about these three perspectives. Method: The search terms ‘schizophrenia’, ‘mental illness’, ‘marriage’, ‘spouse’, ‘partner’, ‘caregiver’, ‘caregiving’, ‘burden’, ‘assortative mating’ and ‘domestic abuse’ were entered into PubMed and Google Scholar. Criteria for inclusion of articles were relevance to the three identified themes of abuse, burden and mental illness in husbands of women with schizophrenia. The results show considerable variation, some of it cultural, with partial evidence for all three characterizations. Conclusion: There is a need for support and psychoeducation programmes that are specifically designated for spouses and that address their special concerns.
The Environmentalism of the Rich and the Privatization of Nature
Authors: Ávila-García Patricia , Sánchez Eduardo Luna 
Published: September 2012

As social property and resources formerly open to common use, such as beaches and coastal lakes, have been privately appropriated, an environmental discourse has arisen among national and transnational elites that justifies this appropriation in terms of conservation and even shapes environmental policies for their benefit. One example is the creation of natural protected areas in zones of predominantly private property, giving them exclusive rights and increasing real estate values and investments in tourism. As a result, tourist paradises have sprung up in places of high biodiversity, offering exclusivity to their owners and clients while violating agrarian rights, creating social conflict, and destroying ecosystems. Frente a un escenario de apropiación privada de espacios otrora de propiedad social y recursos de uso común como playas y lagunas costeras, ha surgido un discurso ecologista de las élites nacionales y transnacionales que justifica esta apropriación por medio de acciones de conservación e incluso orienta las políticas ambientales para su beneficio. Un ejemplo es la creación de áreas naturales protegidas en zonas donde predomina la propiedad privada, con el fin de dar exclusividad y valorizar las inversiones inmobiliarias y turísticas. Como resultado, han surgido paraísos turísticos en lugares de alta biodiversidad que ofrecen exclusividad a sus propietarios y usuarios pero que afectan derechos agrarios, generan conflictos sociales y destruyen ecosistemas.
Mucin 5 Subtype AC Expression and Upregulation in the Nasal Mucosa of Allergic Rhinitis Rats
Authors: Wang Weiwei , Zheng Ming 
Published: September 2012

ObjectiveTo elucidate the functions of nuclear factor kappa B (NF‐κB) in mucin hypersecretion in allergic rhinitis (AR), we examined the in vivo effects of an NF‐κB inhibitor, ammonium pyrrolidine dithiocarbamate (PDTC), on mucin 5 subtype AC (MUC5AC) expression in the nasal mucosa of ovalbumin‐sensitized rats.Study DesignRandomized animal study.SettingAcademic medical center.Subjects and MethodsSprague Dawley rats were randomized into a control group (group A), an AR model group (group B), and an AR model treated with an NF‐κB inhibitor (group C). Rats in groups B and C were sensitized systemically and locally by ovalbumin injection and inhalation, whereas group A was treated with normal saline in place of ovalbumin. Pyrrolidine dithiocarbamate (100 mg/kg/d) was given to group C by intraperitoneal injection for 5 days. NF‐κBp65, MUC5AC, tumor necrosis factor (TNF)–α, and interleukin (IL)–6 were detected by immunohistochemistry, Western blotting, enzyme‐linked immunosorbent assay, or real‐time polymerase chain reaction.ResultsNF‐κB was activated in group B, and significant NF‐κBp65 protein was expressed in the nucleus of cells from the nasal mucosa, resulting in upregulated transcription from TNF‐α and IL‐6 genes, as well as increased contents of TNF‐α and IL‐6 in the nasal lavage fluids. Pyrrolidine dithiocarbamate inhibited nuclear localization of NF‐κBp65 and subsequent downregulation of the transcription and secretion of TNF‐α and IL‐6. MUC5AC was upregulated in group B but reduced in a time‐dependent manner after inhibition of NF‐κB activation.ConclusionNF‐κB activation might induce MUC5AC hypersecretion in AR rats by inflammatory cytokines TNF‐α and IL‐6.
The Effect of Smoking on Ligament and Cartilage Surgery in the Knee
Authors: Kanneganti Praveen , Harris Joshua D. , Brophy Robert H. , Carey James L. , Lattermann Christian , Flanigan David C. 
Published: September 2012

Background: The adverse effects of smoking on various health conditions such as cancer, diabetes, and cardiovascular disease have been well documented. Many orthopaedic conditions, such as fracture healing, wound repair, and bone mineral density, have been reported to be adversely affected by smoking. However, no known systematic reviews have investigated the effects of smoking on ligament and cartilage knee surgery. Purpose: We hypothesized that smoking would have a negative influence from both a basic science and clinical outcome perspective on these types of knee surgeries. Study Design: Systematic review. Methods: A systematic review of multiple medical databases was performed evaluating clinical and basic science studies to determine the effects of smoking on ligament and cartilage knee surgery. Results: Fourteen studies were found for inclusion and analysis. Eight of these studies addressed the relationship between smoking and knee ligaments, and 6 investigated the relationship between smoking and articular cartilage. With the exception of 1, all of the basic science and clinical studies exploring the relationship between smoking and knee ligaments found a negative association of smoking, either molecularly, biomechanically, or clinically. One basic science and 3 clinical studies found a negative influence of smoking on articular cartilage of the knee. No studies were found that investigated the relationship of smoking and menisci. Conclusion: The current literature reveals a negative influence of smoking on the results of knee ligament surgery, both from a basic science and clinical perspective, implying that smoking cessation would benefit patients undergoing these procedures. The association between smoking and knee articular cartilage was less clear, although the literature still suggests an overall negative influence and highlights the need for further investigation.
The Prevalence of Low Back Pain Among Former Elite Cross-Country Skiers, Rowers, Orienteerers, and Nonathletes
Authors: Foss Ida Stange , Holme Ingar , Bahr Roald 
Published: September 2012

Background: Some cross-sectional studies have suggested that the prevalence of low back pain (LBP) may be high among endurance athletes with repetitive back loading, but there are no large, prospective cohort studies addressing this issue. Purpose: To compare the prevalence of symptoms of low back pain (LBP) among former endurance athletes with different loading characteristics on the lumbar region: cross-country skiing (flexion loading), rowing (extension loading), and orienteering (no specific loading), as well as a nonathletic control group. Study design: Cohort study; level of evidence, 2. Methods: Self-reported questionnaire on LBP adapted for sports based on standardized Nordic questionnaires for musculoskeletal symptoms. Responders were 173 rowers, 209 orienteerers, 242 cross-country skiers, and 116 control subjects (88% of the original cohort). Results: There were no group differences between the athletic groups and the control group with regard to the 2 main outcomes: reported LBP the previous 12 months ( P = .66) and frequent LBP the past year (>30 days with LBP) ( P = .14). More rowers than orienteerers reported frequent LBP the past year (adjusted OR = 2.32; CI, 1.02-5.28). Occupational changes due to LBP were reported more often by rowers (13%) than skiers (7%) and orienteerers (3%) ( P = .002). More rowers and skiers reported having received outpatient medical assistance than orienteerers or controls. A training volume >550 h/y was a risk factor for reporting LBP during the previous 12 months compared with a training volume <200 h/y (adjusted OR = 2.51; CI, 1.26-5.02). A previous episode with LBP was associated with LBP later in life (adjusted OR = 3.02; CI, 2.22-4.10). Conclusion: Low back pain was not more common among former endurance athletes with specific back loading compared with non-athletes. The results indicate that years of prolonged and repetitive flexion or extension loading in endurance sports does not lead to more LBP. However, a large training volume in the past year and previous episodes with LBP are risk factors for LBP. Comparing the sports of rowing, cross-country skiing, and orienteering, it appears that whereas orienteering is protective, rowing can provoke LBP.
Repair of Lateral Meniscus Posterior Horn Detachment Lesions
Authors: Schillhammer Carl K. , Werner Frederick W. , Scuderi Matthew G. , Cannizzaro John P. 
Published: September 2012

Background: Posterior horn detachment (PHD) lesions of the lateral meniscus are commonly associated with acute anterior cruciate ligament (ACL) tears. Multiple surgeons have advocated for repair of this lesion at the time of ACL reconstruction. However, the biomechanical consequences of this lesion and its subsequent repair have not been evaluated. Hypothesis: The PHD lesion of the lateral meniscus will lead to increased tibiofemoral contact pressures, and repair of this lesion to bone via a tibial tunnel can restore normal contact pressures during simulated gait. Study Design: Controlled laboratory study. Methods: Lateral compartment contact pressures were measured via a sensor on the tibial plateau in 8 cadaver knees with the knee intact, after sectioning the posterior horn of the lateral meniscus to simulate PHD, and after repairing the injury. The repair was performed using an ACL tunnel guide to drill a tunnel from the anteromedial tibia to the posterior horn attachment site. Dynamic pressure data were continuously collected using a conductive ink pressure sensing system while each knee was moved through a physiological gait flexion cycle. Results: Posterior horn detachment caused a significant increase in tibiofemoral peak contact pressure from 2.8 MPa to 4.2 MPa ( P = .03). After repair of the lesion to bone was performed through a transtibial tunnel, the peak contact pressure was 2.9 MPa. Posterior horn detachment also significantly decreased the maximum contact area over which tibiofemoral pressure is distributed from 451 mm2 in the intact state to 304 mm2 in the detached state. Repair of the PHD lesion increased the maximum contact area to 386 mm2, however, this area was also significantly less than in the intact state ( P = .05). Conclusion: Posterior horn detachment of the lateral meniscus causes increased peak tibiofemoral contact pressure. The peak pressure can be reduced to a normal level with repair of the lesion to bone via a transtibial tunnel. Clinical Relevance: Posterior horn detachment of the lateral meniscus is a lesion often associated with an acute ACL tear. Debate exists concerning the importance of repairing PHD lesions at the time of ACL reconstruction. The data provided in this study may influence surgeons’ management of the lesion.
Bi-musicality in modern Japanese culture
Authors: Tokita Alison 
Published: September 2012

This paper explores bi-musicality in modern Japan, and compares it with bilinguality at societal and individual levels. It considers the usefulness and limitations of the comparison of language and music. It establishes a model of musical competence as a preliminary to considering bi-musical competence, and schematizes the differences between Japanese and Western musical cultures for this purpose. In considering the relevance of bilingualism to the development of bi-musicality as an aspect of bi-culturality, I will argue that bilingualism as such is not so relevant to Japanese music, because early in Japan’s modern period Western music was effectively ‘translated’ into Japanese culture. The application of the concept of bi-musicality to music in modern Japan offers a new perspective on Japan’s musical modernity. The discussion will focus first on the societal level, that is, Japan as a bi-musical culture. Then some individual case studies will be presented of people whose bi-musicality has been central to their musical activity. This will lead to some tentative conclusions about the extent and nature of bi-musicality in Japan.
A non-interventional study of biosimilar granulocyte colony-stimulating factor as prophylaxis for chemotherapy-induced neutropenia in a community oncology centre
Authors: Verpoort Karl , Möhler Thomas M. 
Published: September 2012

Objectives: Prophylaxis with granulocyte colony-stimulating factor (G-CSF) reduces the severity of chemotherapy-induced neutropenia. Biosimilar G-CSF is now approved for use, based on comparable efficacy, safety and quality with the originator product. Methods: We conducted a retrospective review of patients’ charts following the switch from originator G-CSF (Neupogen®) to biosimilar G-CSF (Zarzio®/Filgrastim Hexal®) in a large community oncology practice. A total of 77 consecutive patients with cancer who received biosimilar G-CSF were reviewed, as were 25 patients who received originator G-CSF at the same centre. Results: The median age of patients in the biosimilar G-CSF cohort was 67 years (range 20−83). In this cohort 48% had chemotherapy with a febrile neutropenia risk of >20%. Biosimilar G-CSF was given as primary prophylaxis in 52% and as secondary prophylaxis in 48% of patients. Age and febrile neutropenia in medical history or in previous chemotherapy were factors that triggered the use of G-CSF in patients with a febrile neutropenia risk of <20%. One patient developed febrile neutropenia. Neutropenia led to chemotherapy dose reductions in five patients (6.5%) and discontinuation in two patients (2.5%). No unexpected safety findings were observed. Patient characteristics were generally similar in the originator G-CSF cohort. Only 24% of patients had a febrile neutropenia risk >20% and 36% received primary prophylactic G-CSF. One patient developed febrile neutropenia. Neutropenia led to chemotherapy dose reductions in two patients (8%) and discontinuation in two patients (8%). Conclusions: Biosimilar G-CSF was effective and prevented dose reductions/discontinuation in the majority of patients. Biosimilar G-CSF was considered clinically comparable to its reference product.
A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site
Authors: Nürnberg Sylvia T. , Rendon Augusto , Smethurst Peter A. , Paul Dirk S. , Voss Katrin , Thon Jonathan N. , Lloyd-Jones Heather , Sambrook Jennifer G. , Tijssen Marloes R. ,   the HaemGen Consortium, Italiano Joseph E. , Deloukas Panos , Gottgens Berthold , Soranzo Nicole , Ouwehand Willem H. 
Published: September 2012

AbstractWe recently identified 68 genomic loci where common sequence variants are associated with platelet count and volume. Platelets are formed in the bone marrow by megakaryocytes, which are derived from hematopoietic stem cells by a process mainly controlled by transcription factors. The homeobox transcription factor MEIS1 is uniquely transcribed in megakaryocytes and not in the other lineage-committed blood cells. By ChIP-seq, we show that 5 of the 68 loci pinpoint a MEIS1 binding event within a group of 252 MK-overexpressed genes. In one such locus in DNM3, regulating platelet volume, the MEIS1 binding site falls within a region acting as an alternative promoter that is solely used in megakaryocytes, where allelic variation dictates different levels of a shorter transcript. The importance of dynamin activity to the latter stages of thrombopoiesis was confirmed by the observation that the inhibitor Dynasore reduced murine proplatelet for-mation in vitro.
Gene therapy for adenosine deaminase–deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans
Authors: Candotti Fabio , Shaw Kit L. , Muul Linda , Carbonaro Denise , Sokolic Robert , Choi Christopher , Schurman Shepherd H. , Garabedian Elizabeth , Kesserwan Chimene , Jagadeesh G. Jayashree , Fu Pei-Yu , Gschweng Eric , Cooper Aaron , Tisdale John F. , Weinberg Kenneth I. , Crooks Gay M. , Kapoor Neena , Shah Ami , Abdel-Azim Hisham , Yu Xiao-Jin , Smogorzewska Monika , Wayne Alan S. , Rosenblatt Howard M. , Davis Carla M. , Hanson Celine , Rishi Radha G. , Wang Xiaoyan , Gjertson David , Yang Otto O. , Balamurugan Arumugam , Bauer Gerhard , Ireland Joanna A. , Engel Barbara C. , Podsakoff Gregory M. , Hershfield Michael S. , Blaese R. Michael , Parkman Robertson , Kohn Donald B. 
Published: September 2012

AbstractWe conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)–deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34+ cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m2). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency.