bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole‐gland salvage high‐intensity focused ultrasound therapy for localized prostate cancer recurrence after external beam radiation therapy
Authors: Uddin Ahmed Hashim , Cathcart Paul , Chalasani Venu , Williams Andrew , McCartan Neil , Freeman Alex , Kirkham Alex , Allen Clare , Chin Joseph , Emberton Mark 
Published: November 2011

AbstractBACKGROUND:Whole‐gland high‐intensity focused ultrasound (HIFU) has been used as salvage therapy for local recurrence following external beam radiation therapy for decades. This article describes the use of the Sonablate 500 HIFU system in the salvage setting.METHODS:An evaluation was performed of a consecutive group of men with biochemical failure after external beam radiation therapy with histologically proven local recurrence and bone‐scan and pelvic magnetic resonance imaging to exclude macroscopic metastases, and who chose to have whole‐gland salvage HIFU (Sonablate 500) at 2 centers (3 expert HIFU surgeons at each center). The modified Clavien system was used to categorize adverse events and validated questionnaires for functional outcomes. Progression following HIFU treatment was defined as ASTRO‐Phoenix criteria (prostate serum antigen [PSA] >nadir+2 ng/mL) and/or a positive biopsy and/or start of hormone therapy.RESULTS:Eighty‐four men underwent whole‐gland salvage HIFU (2004‐2009). Median age, pretreatment serum PSA, and biopsy Gleason score was 68 years (range, 64‐72 years), 4.3 ng/mL (range, 1.9‐7.9 ng/mL), and 7 (range, 6‐7), respectively. Mean follow‐up was 19.8 months (range, 3.0‐35.1 months). After salvage HIFU, 62% of the men were pad‐free and leak‐free. Mean International Index of Erectile Function‐5 point score fell from 8.8 to 4.7 (P < .001). International Prostate Symptoms Score and RAND‐SF36 scores were not affected. Two men developed rectourethral fistulae after 1 salvage procedure. A further 2 fistulae occurred in the 6 men undergoing a second salvage HIFU. Intervention for bladder outlet obstruction was needed in 20% (17 of 84 patients). If PSA nonresponders were included, 1‐ and 2‐year progression‐free survival rates were 59% (50 of 84 patients) and 43% (36 of 84 patients), respectively. If PSA nonresponders were excluded, 1‐ and 2‐year progression‐free survival rates were 62% (48 of 77 patients) and 48% (37 of 77 patients), respectively.CONCLUSIONS:Salvage whole‐gland HIFU is a high‐risk procedure. Although its use in early cancer control is promising, strategies to better identify metastatic disease prior to salvage therapy and reduce local toxicity are needed to improve on this. Cancer 2012;118: 3071–78. © 2011 American Cancer Society.
Therapeutic efficacy of combination therapy with intra‐arterial 5‐fluorouracil and systemic pegylated interferon α‐2b for advanced hepatocellular carcinoma with portal venous invasion
Authors: Kasai Kazuhiro , Ushio Akira , Kasai Yukiho , Sawara Kei , Miyamoto Yasuhiro , Oikawa Kanta , Kuroda Hidekatsu , Takikawa Yasuhiro , Suzuki Kazuyuki 
Published: November 2011

AbstractBACKGROUND:The prognosis of advanced hepatocellular carcinoma (HCC) remains poor, particularly among patients with portal vein tumor thrombosis (PVTT). This study evaluated the efficacy of combined 5‐fluorouracil and pegylated interferon (PEG‐IFN) α‐2b in patients with advanced HCC.METHODS:Subjects comprised 59 HCC patients with PVTT treated using subcutaneous administration of PEG‐IFNα‐2b (50‐100 μg on day 1 of each week for 4 weeks) and intra‐arterial infusion of 5‐fluorouracil (250 mg/d for 5 hours on days 1‐5 of each week for 4 weeks). One treatment cycle lasted 4 weeks. The current therapy was discontinued in patients with progressive disease (PD). For responses other than PD, treatment was repeated for ≥1 cycle. The primary efficacy endpoint was the objective early response rate. Secondary efficacy endpoints were progression‐free survival (PFS) and overall survival.RESULTS:Objective early response rate was 73.0%. Cumulative PFS rates were 67.4% at 6 months, 30.2% at 12 months, 25.9% at 18 months, and 20.7% at 24 months. Median PFS was 9.7 months. Cumulative survival rates were 82.4% at 6 months, 73.6% at 12 months, 52.8% at 24 months, and 44.0% at 36 months. Median survival time was 29.9 months. All adverse reactions were controllable by temporary suspension of treatment. Serious complications and treatment‐related deaths were not observed.CONCLUSIONS:Although a prospective randomized controlled trial using a larger population of patients with advanced HCC is needed to evaluate combination therapy with 5‐fluorouracil and PEG‐IFNα‐2b, this new combination therapy may be useful for patients with advanced HCC. Cancer 2011. © 2011 American Cancer Society.
Photodissociation Dynamics of ClCN at Different Wavelengths
Authors: Lutz Stephan , Meuwly Markus 
Published: November 2011

AbstractThe photodissociation dynamics of small molecules in the gas and condensed phase is an important source of information for better characterizing intermolecular interactions. Herein, classical molecular dynamics simulations with provisions to follow reactive processes between different electronic states are used to probe the wavelength dependence of product state distributions after laser excitation of ClCN. It is found that the maximum of the rotational excitation distribution P(j) of the CN product shifts to lower j‐values with increasing wavelength and the width of the distribution narrows. Both observations are in accord with earlier experiments and provide improvements over previous theoretical treatments of the process with the same interaction potentials. For the reaction in a water droplet, strong quenching of rotational excitation is found.
Ca‐Rich Ca–Al‐Oxide, High‐Temperature‐Stable Sorbents Prepared from Hydrotalcite Precursors: Synthesis, Characterization, and CO2 Capture Capacity
Authors: Chang Po‐Hsueh , Chang Yen‐Po , Chen San‐Yuan , Yu Ching‐Tsung , Chyou Yau‐Pin 
Published: November 2011

AbstractWe present the design and synthesis of Ca‐rich Ca–Al–O oxides, with Ca2+/Al3+ ratios of 1:1, 3:1, 5:1, and 7:1, which were prepared by hydrothermal decomposition of coprecipitated hydrotalcite‐like Ca–Al–CO3 precursors, for high‐temperature CO2 adsorption at 500–700 °C. In situ X‐ray diffraction measurements indicate that the coprecipitated, Ca‐rich, hydrotalcite‐like powders with Ca2+/Al3+ ratios of 5:1 and 7:1 contained Ca(OH)2 and layered double hydroxide (LDH) phases. Upon annealing, LDH was first destroyed at approximately 200 °C to form an amorphous matrix, and then at 450–550 °C, the Ca(OH)2 phase was converted into a CaO matrix with incorporated Al3+ to form a homogeneous solid solution without a disrupted lattice structure. CaO nanocrystals were grown by thermal treatment of the weakly crystalline Ca–Al–O oxide matrix. Thermogravimetric analysis indicates that a CO2 adsorption capacity of approximately 51 wt. % can be obtained from Ca‐rich Ca–Al–O oxides prepared by calcination of 7:1 Ca–Al–CO3 LDH phases at 600–700 °C. Furthermore, a relatively high CO2 capture capability can be achieved, even with gas flows containing very low CO2 concentrations (CO2/N2=10 %). Approximately 95.6 % of the initial CO2 adsorption capacity of the adsorbent is retained after 30 cycles of carbonation–calcination. TEM analysis indicates that carbonation‐promoted CaCO3 formation in the Ca–Al–O oxide matrix at 600 °C, but a subsequent desorption in N2 at 700 °C, caused the formation CaO nanocrystals of approximately 10 nm. The CaO nanocrystals are widely distributed in the weakly crystalline Ca–Al–O oxide matrix and are present during the carbonation–calcination cycles. This demonstrates that Ca–Al–O sorbents that developed through the synthesis and calcination of Ca‐rich Ca–Al LDH phases are suitable for long‐term cyclic operation in severe temperature environments.
Fulminant type 1 diabetes—an important subtype in East Asia
Authors: Imagawa Akihisa , Hanafusa Toshiaki 
Published: November 2011

AbstractFulminant type 1 diabetes is defined as a subtype of type 1 diabetes with a remarkably acute onset. A nationwide survey identified that this variant accounts for approximately 20% of acute‐onset type 1 diabetic patients in Japan. Recent studies indicate that this is not a minor subtype in other East Asian countries. As genetic factors, we revealed association of HLA‐DR‐DQ, HLA‐B and CTLA‐4 to fulminant type 1 diabetes. As an environmental factor, viral infection would contribute to the development of this subtype. Cellular infiltration to islets was detected soon after the onset but not observed 1 month after the onset. Macrophages and T cells were the main components of the infiltrates. Enterovirus RNA and Toll‐like receptor‐3 expression, a signature of viral infection, was also observed. These findings suggest that viral infection in the susceptible individual might trigger anti‐viral immune response and that pancreatic beta cells are rapidly destroyed through the accelerated immune reaction. Copyright © 2011 John Wiley & Sons, Ltd.
Heterogeneity among patients with latent autoimmune diabetes in adults
Authors: Maruyama Taro , Nakagawa Terumichi , Kasuga Akira , Murata Mitsuru 
Published: November 2011

AbstractBackgroundSome type 1 diabetic patients do not require insulin at diagnosis of diabetes, and they progress to insulin dependence only after several years (latent autoimmune diabetes in adults). However, not all patients with latent autoimmune diabetes in adults progress to insulin dependence. We compared the characteristics of patients with high glutamic acid decarboxylase antibodies (GADA) titres (≥10 U/mL) to those of patients with low titres and examined other factors possibly associated with the progression to insulin dependence.MethodsWe began registering diabetic patients in 1993 and have since followed them prospectively. Among these patients, we analysed clinical characteristics and progression to insulin dependence in those followed for more than 5 years.ResultsPatients with high GADA titres were younger and had lower body mass index, shorter disease durations and lower serum C‐peptide (s‐CPR) levels than the patients with low GADA titre and GADA negative type 2 diabetes. Frequencies of other islet‐related autoantibodies were significantly higher in patients with high GADA titre than in those with low GADA titres. Disease protective HLA class II genotypes were less frequent in patients with high titre. The positive predictive value of being GADA positive was only 42.7%. The positive predictive value increased to 78.6% when the cut‐off was set at the relatively high level of 10 U/mL. Combining GADA with other islet‐related autoantibodies or HLA class II genotype increased positive predictive value but decreased sensitivity.ConclusionsOur results suggest that latent autoimmune diabetes in adults constitutes a heterogeneous group and that the majority of patients with high GADA titres (≥10 U/mL) will ultimately develop type 1 diabetes while those with low titres include patients with type 1 and type 2 diabetes. Copyright © 2011 John Wiley & Sons, Ltd.
Immunology of Diabetes Society T‐Cell Workshop: HLA class I tetramer‐directed epitope validation initiative T‐Cell Workshop Report—HLA Class I Tetramer Validation Initiative
Authors: Mallone R. , Scotto M. , Janicki C. N. , James E. A. , Fitzgerald‐Miller L. , Wagner R. , Gottlieb P. , Thorpe J. , Jospe N. , Durinovic‐Bellò I. , Boitard C. , Lou O. , Dayan C. M. , Wong F. S. ,   T‐Cell Workshop Committee, Immunology of Diabetes Society
Published: November 2011

AbstractBackgroundIdentification of T‐cell reactivity to β‐cell antigen epitopes is an important goal for studying pathogenesis and for designing and monitoring of immunotherapeutic interventions in type 1 diabetes (T1D).MethodsWe performed a multicentre validation of known human leukocyte antigen (HLA) class I CD8+ T‐cell epitopes. To this end, peripheral blood T‐cell responses were measured in 35 recently (<2 years) diagnosed HLA‐A*02:01+ T1D patients using blind‐coded HLA‐A2 tetramers (TMrs) and pentamers (PMrs), encompassing two epitopes of preproinsulin (PPI; PPI$\def\endash{\hbox{--}} _{\rm{A12\endash 20}}$ and PPI$\def\endash{\hbox{--}} _{\rm{B10\endash 18}}$) and two epitopes of glutamic acid decarboxylase (GAD; GAD114–122 and GAD536–545). We also compared the readout of TMrs and PMrs with a CD8+ T‐cell interferon‐γ enzyme‐linked immunospot assay.ResultsDespite the minute frequencies of autoreactive cells detected by TMrs/PMrs, most (73–77%) T1D patients had responses to one or more of the epitopes used. All four epitopes were recognized by T1D patients, with a prevalence ranging from 5 to 25%. TMrs and PMrs detected more positive responses to the β‐cell epitopes than CD8+ T‐cell interferon‐γ enzyme‐linked immunospot. However, concordance between positive responses to TMrs and PMrs was limited.ConclusionsUsing a multicentre blind‐coded setup and three different T‐cell assays, we have validated PPI and GAD epitopes as commonly recognized CD8+ T‐cell targets in recently diagnosed T1D patients. Both TMrs and PMrs showed higher detection sensitivity than the CD8+ T‐cell interferon‐γ enzyme‐linked immunospot assay. However, there are some important methodological issues that need to be addressed in using these sensitive techniques for detecting low frequency responses. Copyright © 2011 John Wiley & Sons, Ltd.
Immunology of Diabetes Society T‐Cell Workshop: HLA class II tetramer‐directed epitope validation initiative
Authors: James E. A. , Mallone R. , Schloot N. C. , Gagnerault M. C. , Thorpe J. , Fitzgerald‐Miller L. , Reichow J. , Wagner R. , Pham M. N. , Jospe N. , Lou O. , Gottlieb P. A. , Brooks‐Worrell B. M. , Durinovic‐Belló Ivana ,   T‐Cell Workshop Committee, Immunology of Diabetes Society
Published: November 2011

AbstractBackgroundIslet‐antigen‐specific CD4+ T cells are known to promote auto‐immune destruction in T1D. Measuring T‐cell number and function provides an important biomarker. In response to this need, we evaluated responses to proinsulin and GAD epitopes in a multicentre study.MethodsA tetramer‐based assay was used in five participating centres to measure T‐cell reactivities to DR0401‐restricted epitopes. Three participating centres concurrently performed ELISPOT or immunoblot assays. Each centre used blind‐coded, centrally distributed peptide and tetramer reagents.ResultsAll participating centres detected responses to auto‐antigens and the positive control antigen, and in some cases cloned the corresponding T cells. However, response rates varied among centres. In total, 74% of patients were positive for at least one islet epitope. The most commonly recognized epitope was GAD270–285. Only a minority of the patients tested by tetramer and ELISPOT were concordant for both assays.ConclusionsThis study successfully detected GAD and proinsulin responses using centrally distributed blind‐coded reagents. Centres with little previous experience using class II tetramer reagents implemented the assay. The variability in response rates observed for different centres suggests technical difficulties and/or heterogeneity within the local patient populations tested. Dual analysis by tetramer and ELISPOT or immunoblot assays was frequently discordant, suggesting that these assays detect distinct cell populations. Future efforts should investigate shared blood samples to evaluate assay reproducibility and longitudinal samples to identify changes in T‐cell phenotype that correlate with changes in disease course. Copyright © 2011 John Wiley & Sons, Ltd.
Imaging of pancreatic islet cells
Authors: Arifin Dian R. , Bulte Jeff W.M. 
Published: November 2011

AbstractAt present, the onset and progress of diabetes, and the efficacy of potential treatments, can only be assessed through indirect means, i.e. blood glucose, insulin, or C‐peptide measurements. The development of non‐invasive and reliable methods for (1) quantification of pancreatic beta islet cell mass in vivo, (2) determining endogenous islet function and survival, and (3) visualizing the biodistribution, survival, and function of transplanted exogenous islets are critical to further advance both basic science research and islet cell therapy in diabetes. Islet cell imaging using magnetic resonance, bioluminescence, positron emission tomography, or single photon emission computed tomography may provide us with a direct means to interrogate islet cell distribution, survival, and function. Current state‐of‐the‐art strategies for beta‐cell imaging are discussed and reviewed here in context of their clinical relevance. Copyright © 2011 John Wiley & Sons, Ltd.
Insulin as a key autoantigen in the development of type 1 diabetes
Authors: Nakayama Maki 
Published: November 2011

AbstractType 1 diabetes is a T‐cell‐mediated autoimmune disease against pancreatic beta cells. T cells target various antigens such as insulin, chromogranin A, glutamic acid decarboxylase and islet‐specific glucose‐6‐phosphatase catalytic subunit‐related protein. Elimination of insulin dramatically prevents diabetes in the non‐obese diabetic (NOD) mouse model and response to insulin occurs prior to that to other antigens. These findings suggest that insulin is a target antigen at the early stage of the disease and is likely to be essential to cause anti‐islet autoimmunity in NOD mice. In this review, we discuss whether insulin is truly essential and is only the single essential autoantigen for NOD mice and potentially for man. Although the ultimate principle is still being addressed, it is certain that T‐cell response to insulin is a major check point to develop type 1 diabetes in NOD mice. Given multiple similarities between diabetes of NOD mice and man, targeting insulin and insulin‐reactive T cells may provide opportunities to develop robust immunotherapies. Copyright © 2011 John Wiley & Sons, Ltd.
Immunization with an insulin peptide–MHC complex to prevent type 1 diabetes of NOD mice
Authors: Zhang Li , Stadinski Brian D. , Michels Aaron , Kappler John W. , Eisenbarth George S. 
Published: November 2011

AbstractBackgroundMutating the insulin B:9–23 peptide prevents diabetes in NOD mice. Thus, the trimolecular complex of I‐A$^{\rm{g7}}$‐insulin B:9–23 peptide‐TCR may be essential for the development of spontaneous diabetes. Pathogenic T cells recognize the B:9–23 peptide presented by I‐A$^{\rm{g7}}$ in what is termed register 3, with the B22 basic amino acid (arginine) of the peptide bound in pocket 9 of I‐A$^{\rm{g7}}$. Our hypothesis is that immunization with an insulin B:12–22 peptide linked to I‐A$^{\rm{g7}}$ in register 3 (I‐A$^{\rm{g7}}$‐B:RE#3 complex) can induce specific antibodies to the complex, block pathogenic TCRs, and thus prevent diabetes.MethodsWe immunized young NOD mice with recombinant I‐A$^{\rm{g7}}$‐B:RE#3 protein, in which two amino acids of the peptide were mutated to fix the peptide in register 3, and investigated the induced antibodies targeted to the peptide in register 3.ResultsSpecific antibodies targeting I‐A$^{\rm{g7}}$‐B:RE#3 but not I‐A$^{\rm{g7}}$‐HEL were identified in the sera of I‐A$^{\rm{g7}}$‐B:RE#3 immunized mice. The sera inhibited B:9–23‐induced T‐cell responses in vitro. I‐A$^{\rm{g7}}$‐B:RE#3 immunization delayed progression to diabetes (versus PBS, p = 0.0005), while immunization with I‐A$^{\rm{g7}}$‐HEL control complex did not.ConclusionsImmunization with I‐A$^{\rm{g7}}$‐B:RE#3 complex significantly delays the development of insulin autoantibodies and the onset of diabetes in NOD mice, which is associated with the induction of I‐A$^{\rm{g7}}$‐B:RE#3 antibodies. Copyright © 2011 John Wiley & Sons, Ltd.
Innate immunity in type 1 diabetes
Authors: Zipris Danny 
Published: November 2011

AbstractBackgroundRat models of diabetes have emerged as a powerful experimental tool for addressing the role of microbial pathogens in the mechanism of autoimmune diabetes. We have used the biobreeding diabetes resistant and LEW1.WR1 rat models to identify the role of virus‐induced innate immunity in the mechanism of type 1 diabetes.MethodsGroups of rats 21–25 days of age were left untreated, injected i.p. with 1 × 107PFU of Kilham rat virus (KRV) only, or with 1–3 µg/g body‐weight‐purified toll‐like receptor agonists on three consecutive days and infected with 1 × 107PFU of KRV on the following day. Spleens and pancreatic lymph nodes were recovered 5 days after infection and used for gene array analysis. To test the role of inflammation in diabetes, rats injected with KRV only or Poly(I:C) plus KRV were also administered with 2 or 0.2 µg/g body weight of dexamethasone and followed for diabetes for 40 days.ResultsKRV induced the expression of a vast array of proinflammatory genes in pancreatic lymph nodes on day 5 following infection. Brief dexamethasone therapy downmodulated inflammation and completely blocked diabetes.ConclusionsOur data suggest a strong association between early virus‐induced proinflammatory responses and islet destruction and raise the possibility that targeting innate immune pathways in the early stages of diabetes may be a useful strategy for disease prevention. Copyright © 2011 John Wiley & Sons, Ltd.
Genetic association analyses of atopic illness and proinflammatory cytokine genes with type 1 diabetes
Authors: Saleh Nada M. , Raj Srilakshmi M. , Smyth Deborah J. , Wallace Chris , Howson Joanna M. M. , Bell Louise , Walker Neil M. , Stevens Helen E. , Todd John A. 
Published: November 2011

AbstractBackgroundThe genetic basis of the autoimmune disease type 1 diabetes (T1D) has now been largely determined, so now we can compare these findings with emerging genetic knowledge of disorders and phenotypes that have been negatively or positively associated with T1D historically. Here, we assessed the role in T1D of variants previously reported to be associated with atopic diseases and epithelial barrier function, profilaggrin (), and those that affect the expression levels of the proinflammatory cytokines tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β, interferon (IFN)γ and IL‐18.MethodsWe genotyped single nucleotide polymorphisms (SNPs): − 105/rs28665122 in SELS or SEPS1 (selenoprotein), three single nucleotide polymorphisms in IL18 (−105/rs360717, + 183/rs5744292 and + 1467/rs574456) and R501X/rs61816761 in FLG, the major locus associated with atopic dermatitis and predisposing to asthma, in a minimum of 6743 T1D cases and 7864 controls.ResultsNo evidence of T1D association was found for any of the SNPs we genotyped at FLG, SELS or IL18 (p ≥ 0.03), nor with haplotypes of IL18 (p = 0.82). Review of previous T1D genome‐wide association results revealed that four (human leucocyte antigen (HLA), gasdermin B/ORM1 (Saccharomyces cerevisiae)‐like/gasdermin B/, GSDMB/ORMDL3/GSDMA and IL2RB) of ten loci recently reported to be associated with asthma were associated with T1D (p⩽0.005).ConclusionsThese results show that there are shared genetic associations for atopy‐related traits and T1D, and this might help in the future to understand the mechanisms, pathways and environmental factors that underpin the rapid rise in incidence of both disorders in children. Copyright © 2011 John Wiley & Sons, Ltd.