bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole pelvic helical tomotherapy for locally advanced cervical cancer: technical implementation of IMRT with helical tomothearapy
Authors: Hsieh Chen-Hsi , Wei Ming-Chow , Lee Hsing-Yi , Hsiao Sheng-Mou , Chen Chien-An , Wang Li-Ying , Hsieh Yen-Ping , Tsai Tung-Hu , Chen Yu-Jen , Shueng Pei-Wei 
Published: December 2009

Abstract

Background
To review the experience and to evaluate the treatment plan of using helical tomotherapy (HT) for the treatment of cervical cancer.

Methods
Between November 1st, 2006 and May 31, 2009, 10 cervical cancer patients histologically confirmed were enrolled. All of the patients received definitive concurrent chemoradiation (CCRT) with whole pelvic HT (WPHT) followed by brachytherapy. During WPHT, all patients were treated with cisplatin, 40 mg/m2 intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0).

Results
The mean survival was 25 months (range, 3 to 27 months). The actuarial overall survival, disease-free survival, locoregional control and distant metastasis-free rates at 2 years were 67%, 77%, 90% and 88%, respectively. The average of uniformity index and conformal index was 1.06 and 1.19, respectively. One grade 3 of acute toxicity for diarrhea, thrombocytopenia and three grade 3 leucopenia were noted during CCRT. Only one grade 3 of subacute toxicity for thrombocytopenia was noted. There were no grade 3 or 4 subacute toxicities of anemia, leucopenia, genitourinary or gastrointestinal effects. Compared with conventional whole pelvic radiation therapy (WPRT), WPHT decreases the mean dose to rectum, bladder and intestines successfully.

Conclusion
HT provides feasible clinical outcomes in locally advanced cervical cancer patients. Long-term follow-up and enroll more locally advanced cervical carcinoma patients by limiting bone marrow radiation dose with WPHT technique is warranted.
Investigation of the cerebral blood flow of an Omani man with supposed ‘spirit possession’ associated with an altered mental state : a case report
Authors: Guenedi Amr A , Al Hussaini Ala'Alddin , Obeid Yousif A , Hussain Samir , Al-Azri Faisal , Al-Adawi Samir 
Published: December 2009

Abstract

Introduction
The view that spirits may possess humans is found in 90% of the world population, including Arab/Islamic societies. Despite the association between possessive states and various neurological and psychiatric disorders, the available literature has yet to correlate possessive states with functional brain imaging modalities such as single-photon-emission computed tomography.

Case presentation
This paper describes the clinical case of a 22-year-old male Omani patient who presented to us with an altered state of consciousness that his caregiver attributed to possession. We examined whether the patient's mental state correlated with neuro-imaging data. The patient's distress was invariably associated with specific perfusion in the left temporal lobe and structural abnormality in the left basal ganglia.

Conclusion
We discuss the case in the context of possession as a culturally sanctioned idiom of distress, and highlight the importance of studying cross-cultural presentations of altered states of consciousness within biomedical models.
RANKL inhibition by osteoprotegerin prevents bone loss without affecting local or systemic inflammation parameters in two rat arthritis models: comparison with anti-TNFα or anti-IL-1 therapies
Authors: Stolina Marina , Schett Georg , Dwyer Denise , Vonderfecht Steven , Middleton Scot , Duryea Diane , Pacheco Efrain , Van Gwyneth , Bolon Brad , Feige Ulrich , Zack Debra , Kostenuik Paul 
Published: December 2009

Abstract
Introduction
Rat adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) feature bone loss and systemic increases in TNFα, IL-1β, and receptor activator of NF-κB ligand (RANKL). Anti-IL-1 or anti-TNFα therapies consistently reduce inflammation in these models, but systemic bone loss often persists. RANKL inhibition consistently prevents bone loss in both models without reducing joint inflammation. Effects of these therapies on systemic markers of bone turnover and inflammation have not been directly compared.

Methods
Lewis rats with established AIA or CIA were treated for 10 days (from day 4 post onset) with either PBS (Veh), TNFα inhibitor (pegsunercept), IL-1 inhibitor (anakinra), or RANKL inhibitor (osteoprotegerin (OPG)-Fc). Local inflammation was evaluated by monitoring hind paw swelling. Bone mineral density (BMD) of paws and lumbar vertebrae was assessed by dual X-ray absorptiometry. Markers and mediators of bone resorption (RANKL, tartrate-resistant acid phosphatase 5b (TRACP 5B)) and inflammation (prostaglandin E2 (PGE2), acute-phase protein alpha-1-acid glycoprotein (α1AGP), multiple cytokines) were measured in serum (day 14 post onset).

Results
Arthritis progression significantly increased paw swelling and ankle and vertebral BMD loss. Anti-TNFα reduced paw swelling in both models, and reduced ankle BMD loss in AIA rats. Anti-IL-1 decreased paw swelling in CIA rats, and reduced ankle BMD loss in both models. Anti-TNFα and anti-IL-1 failed to prevent vertebral BMD loss in either model. OPG-Fc reduced BMD loss in ankles and vertebrae in both models, but had no effect on paw swelling. Serum RANKL was elevated in AIA-Veh and CIA-Veh rats. While antiTNFα and anti-IL-1 partially normalized serum RANKL without any changes in serum TRACP 5B, OPG-Fc treatment reduced serum TRACP 5B by over 90% in both CIA and AIA rats. CIA-Veh and AIA-Veh rats had increased serum α1AGP, IL-1β, IL-8 and chemokine (C-C motif) ligand 2 (CCL2), and AIA-Veh rats also had significantly greater serum PGE2, TNFα and IL-17. Anti-TNFα reduced systemic α1AGP, CCL2 and PGE2 in AIA rats, while anti-IL-1 decreased systemic α1AGP, IL-8 and PGE2. In contrast, RANKL inhibition by OPG-Fc did not lessen systemic cytokine levels in either model.

Conclusions
Anti-TNFα or anti-IL-1 therapy inhibited parameters of local and systemic inflammation, and partially reduced local but not systemic bone loss in AIA and CIA rats. RANKL inhibition prevented local and systemic bone loss without significantly inhibiting local or systemic inflammatory parameters.
Serum levels of autoantibodies against C-reactive protein correlate with renal disease activity and response to therapy in lupus nephritis
Authors: Sjöwall Christopher , Zickert Agneta , Skogh Thomas , Wetterö Jonas , Gunnarsson Iva 
Published: December 2009

Abstract
Introduction
Serum levels of C-reactive protein (CRP) seldom reflect disease activity in systemic lupus erythematosus (SLE). We have previously shown that autoantibodies against neo-epitopes of CRP often occur in SLE, but that this does not explain the modest CRP response seen in flares. However, we have repeatedly found that anti-CRP levels parallel lupus disease activity, with highest levels in patients with renal involvement; thus, we aimed to study anti-CRP in a material of well-characterized lupus nephritis patients.

Methods
Thirty-eight patients with lupus nephritis were included. Treatment with corticosteroids combined with cyclophosphamide, mycophenolate mofetil or rituximab was started after baseline kidney biopsy. A second biopsy was taken after ≥ 6 months. Serum creatinine, cystatin C, complement, anti-dsDNA, anti-CRP and urinalysis were done on both occasions. Biopsies were evaluated regarding World Health Organisation (WHO) class and indices of activity and chronicity. Renal disease activity was estimated using the British Isles Lupus Assessment Group (BILAG) index.

Results
At baseline, 34/38 patients had renal BILAG-A; 4/38 had BILAG-B. Baseline biopsies showed WHO class III (n = 8), IV (n = 19), III to IV/V (n = 3) or V (n = 8) nephritis. Seventeen out of 38 patients were anti-CRP-positive at baseline, and six at follow-up. Overall, anti-CRP levels had dropped at follow-up (P < 0.0001) and anti-CRP levels correlated with renal BILAG (r = 0.29, P = 0.012). A positive anti-CRP test at baseline was superior to anti-dsDNA and C1q in predicting poor response to therapy as judged by renal BILAG. Baseline anti-CRP levels correlated with renal biopsy activity (r = 0.33, P = 0.045), but not with chronicity index. Anti-CRP levels were positively correlated with anti-dsDNA (fluorescence-enhanced immunoassay: r = 0.63, P = 0.0003; Crithidia luciliae immunofluorescence microscopy test: r = 0.44, P < 0.0001), and inversely with C3 (r = 0.35, P = 0.007) and C4 (r = 0.29, P = 0.02), but not with C1q (r = 0.14, P = 0.24). No associations with urinary components, creatinine, cystatin C or the glomerular filtration rate were found.

Conclusions
In the present study, we demonstrate a statistically significant correlation between anti-CRP levels and histopathological activity in lupus nephritis, whereas a baseline positive anti-CRP test predicted poor response to therapy. Our data also confirm previous findings of associations between anti-CRP and disease activity. This indicates that anti-CRP could be helpful to assess disease activity and response to therapy in SLE nephritis, and highlights the hypothesis of a pathogenetic role for anti-CRP antibodies in lupus nephritis.
Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza
Authors: Bermejo-Martin Jesus F , Ortiz de Lejarazu Raul , Pumarola Tomas , Rello Jordi , Almansa Raquel , Ramírez Paula , Martin-Loeches Ignacio , Varillas David , Gallegos Maria C , Serón Carlos , Micheloud Dariela , Gomez JoseManuel , Tenorio-Abreu Alberto , Ramos María J , Molina MLourdes , Huidobro Samantha , Sanchez Elia , Gordón Mónica , Fernández Victoria , del Castillo Alberto , Marcos MaÁngeles , Villanueva Beatriz , López CarlosJavier , Rodríguez-Domínguez Mario , Galan Juan-Carlos , Cantón Rafael , Lietor Aurora , Rojo Silvia , Eiros Jose M , Hinojosa Carmen , Gonzalez Isabel , Torner Nuria , Banner David , Leon Alberto , Cuesta Pablo , Rowe Thomas , Kelvin David J 
Published: December 2009

Abstract
Introduction
Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1.

Methods
We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene.

Results
Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients.

Conclusions
While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.
Pivotal Advance: Bifidobacteria and Gram-negative bacteria differentially influence immune responses in the proinflammatory milieu of celiac disease
Authors: De Palma G , Cinova J , Stepankova R , Tuckova L , Sanz Y 
Published: December 2009

Abstract
Immunomodulatory effects of intestinal bacteria under the immune (IFN-γ) and environmental triggers (gliadins) of celiac disease on peripheral blood mononuclear cells.
CD is a chronic inflammatory disorder of the small intestine that presents in genetically predisposed individuals following gluten consumption. In this study, the effects of Bifidobacterium (Bifidobacterium bifidum IATA-ES2 and Bifidobacterium longum ATCC15707) and Gram-negative bacteria (Bacteroides fragilis DSM2451, Escherichia coli CBL2, and Shigella CBD8 isolated from CD patients), alone and in the presence of CD triggers (gliadins and/or IFN-γ) on surface marker expression and cytokine production by PBMCs, were determined. These effects were also evaluated in cocultures of PBMCs and Caco-2 cells. The Gram-negative bacteria induced higher secretion of Th1-type proinflammatory cytokines (IL-12 and/or IFN-γ) than the Bifidobacterium strains. Shigella CBD8 and E. coli CBL2 up-regulated mainly HLA-DR and CD40 expression involved in Th1 activation, and Bifidobacterium strains up-regulated CD83 expression. Specific interactions among the studied bacteria, gliadins, and IFN-γ, which favored the CD immune features, were also detected. Therefore, intestinal bacteria could be additional factors that regulate the ability of monocytes recruited to the mucosa to respond to gliadins and IFN-γ in CD patients, influencing the course of the disease.
The Bottleneck in the Cancer Biomarker Pipeline and Protein Quantification through Mass Spectrometry–Based Approaches: Current Strategies for Candidate Verification
Authors: Makawita Shalini , Diamandis Eleftherios P 
Published: December 2009

AbstractBackground: Although robust discovery-phase platforms have resulted in the generation of large numbers of candidate cancer biomarkers, a comparable system for subsequent quantitative assessment and verification of all candidates is lacking. Established immunoassays and available antibodies permit analysis of small subsets of candidates; however, the lack of commercially available reagents, coupled with high costs and lengthy production and purification times, have rendered the large majority of candidates untestable.Content: Mass spectrometry (MS), and in particular multiple reaction monitoring (MRM)-MS, has emerged as an alternative technology to immunoassays for quantification of target proteins. Novel biomarkers are expected to be present in serum in the low (μg/L–ng/L) range, but analysis of complex serum or plasma digests by MS has yielded milligram per liter limits of detection at best. The coupling of prior sample purification strategies such as enrichment of target analytes, depletion of high-abundance proteins, and prefractionation, has enabled reliable penetration into the low microgram per liter range. This review highlights prospects for candidate verification through MS-based methods. We first outline the biomarker discovery pipeline and its existing bottleneck; we then discuss various MRM-based strategies for targeted protein quantification, the applicability of such methods for candidate verification, and points of concern.Summary: Although it is unlikely that MS-based protein quantification will replace immunoassays in the near future, with the expected improvements in limits of detection and specificity in instrumentation, MRM-based approaches show great promise for alleviating the existing bottleneck to discovery.
Quantification of Serum 1–84 Parathyroid Hormone in Patients with Hyperparathyroidism by Immunocapture In Situ Digestion Liquid Chromatography–Tandem Mass Spectrometry
Authors: Kumar Vivek , Barnidge David R , Chen Li-Sheng , Twentyman Jolaine M , Cradic Kendall W , Grebe Stefan K , Singh Ravinder J 
Published: December 2009

Abstract
Background: Immunoassays specific for 1–84 parathyroid hormone (PTH) reportedly reflect the bioactivity of PTH; however, PTH immunoassays can be susceptible to interference by cross-reacting PTH fragments. In addition, these assays currently lack standardization. A methodology using immunocapture purification with liquid chromatography–tandem mass spectrometry (LC-MS/MS) detection, along with a stable isotope–labeled internal standard, may help address these issues.
Methods: We isolated 1–84 PTH from 1 mL serum by immunocapture on a 6.5-mm polystyrene bead. The immobilized PTH was digested in situ and analyzed by LC-MS/MS. For quantification, we used the selected reaction monitoring response from the N-terminal tryptic peptide 1–13 PTH (1SVSEIQLMHNLGK13).
Results: The linear range of the assay was 39.1–4560 ng/L, and the limit of detection and limit of quantification were 14.5 ng/L and 39.1 ng/L, respectively. The intraassay CVs ranged from 6% to 11%, and the interassay CVs ranged from 7% to 17%. Interference by PTH fragments 1–44 PTH, 7–84 PTH, 43–68 PTH, 52–84 PTH, 64–84 PTH, and PTH-related protein (PTHrP) was ≤1% to ≤0.001%. Method comparison of LC-MS/MS vs the Roche Cobas® immunoassay yielded Deming fit of LC-MS/MS = 1.01x immunoassay – 13.21. The mean bias by Bland–Altman plot was −9.4%.
Conclusions: In patients with hyperparathyroidism, the immunocapture in situ digestion LC-MS/MS method can provide accurate and precise PTH results compared with immunoassay.
Prevalence of Weight Concerns and Obesity Among Smokers Calling a Quitline
Authors: Bush Terry , Levine Michele D. , Deprey Mona , Cerutti Barbara , Zbikowski Susan M. , McAfee Tim , Mahoney Lisa , Beebe Laura 
Published: December 2009

AbstractBackground: Cessation-related weight gain and weight concerns are common among smokers and have a negative impact on quitting. Obese smokers tend to gain more than the average amount of weight and also have lower quit rates. This article describes the prevalence of obesity and weight concerns among smokers calling a state quitline in the United States. Results: Among 3972 smokers using a state quitline, 33.3% were obese, 30.2% overweight, 33.3% normal weight and 3.2% under-weight; a total of 60.6% were concerned about cessation-related weight gain. Compared with non-obese callers, obese callers were more likely to be female, Hispanic, non-White and heavier smokers. Conclusions: This is the first study to report data on body weight and weight concerns of smokers calling a national quitline. Given the lower quit rates among obese and weight-concerned smokers, and the burden of smoking and obesity, there is an opportunity to develop new treatment approaches for this at-risk population.
Understanding Former Smokers in Canada: Examining Who They are and When, Why and How They Quit
Authors: Ismailov Rovshan M. , Leatherdale Scott T. 
Published: December 2009

AbstractObjectives: Although the benefits of smoking cessation are well established, long-term abstinence from cigarettes is difficult for many smokers to achieve. We aimed to examine quit attempts, years since quitting and factors associated with long-term abstinence among former smokers.Methods: Data were from the 2006 Canadian Tobacco Use Monitoring Survey. Descriptive analyses were performed and logistic regression models were used to examine factors associated with long-term abstinence (more than 5 years) among former smokers.Results: In 2006, over one in four Canadians (27.1%,n= 7,200,000) aged 15 and older was a former smoker. The prevalence of former smoking was higher among men (30.9%) in comparison to women (23.4%). Former smokers who quit in the past 3 years or earlier were more likely to be older as well as have children younger than 15 in the household. Logistic regression analyses revealed that older age was a significant predictor of long-term abstinence from smoking.Conclusion: Our findings suggest that there are modifiable characteristics associated with long-term smoking abstinence that could be addressed by relapse prevention programming. Longitudinal data are warranted to further clarify the relationship between certain characteristic of former smokers and the duration of abstinence.
Sensitivity Analysis of the Efficacy of Varenicline in Smoking Cessation With a Special Reference to Study Dropouts
Authors: Oshima Akira , Ito Yuri , Nomura Hideki 
Published: December 2009

AbstractWe conducted a sensitivity analysis under four scenarios using data from three Asian studies conducted with low dropout rates to evaluate the efficacy of varenicline in smoking cessation within a scenario where dropouts from the study are dealt with in a manner as unfavourable as possible to varenicline. Pooled odds ratio of continuous abstinence at week 24 was 1.55 (95% confidence interval: 1.03–2.35, random-effect model) under the scenario where dropouts from the varenicline group were dealt with as smokers and those from the placebo group as successful quitters. From the present study, the efficacy of varenicline has been firmly established in the Asian population.
The Case for Chemotherapy Only for Localized Hodgkin Lymphoma
Authors: Straus David J. 
Published: December 2009

Abstract
Although radiation therapy (RT) alone, and more recently in combination with chemotherapy, has been the cornerstone of curative treatment for early-stage Hodgkin lymphoma for &gt;40 years, the late toxicities of this treatment are increasingly being recognized as causes of significant late morbidity and mortality. In recent years, the focus of treatment of early-stage Hodgkin lymphoma has been reductions in the doses and fields of RT and attempts to reduce the amount and the toxicity of chemotherapy. Another approach has been to treat with chemotherapy alone and to eliminate RT entirely unless it is absolutely necessary. This review summarizes the accumulating information on the late side effects of treatment of Hodgkin lymphoma, the results of trials with chemotherapy only, attempts to reduce the toxicity of chemotherapy, and the new role of positron emission tomography in treatment planning.