bluuebunny/crossref_metadata_2025_split huggingface dataset:
The adipokine adiponectin has potent anti-fibrotic effects mediated via adenosine monophosphate-activated protein kinase: novel target for fibrosis therapy
Authors: Fang Feng , Liu Lei , Yang Yang , Tamaki Zenshiro , Wei Jun , Marangoni Roberta G , Bhattacharyya Swati , Summer Ross S , Ye Boping , Varga John 
Published: October 2012

Abstract
Introduction
Fibrosis in scleroderma is associated with collagen deposition and myofibroblast accumulation. Peroxisome proliferator activated receptor gamma (PPAR-γ), a master regulator of adipogenesis, inhibits profibrotic responses induced by transforming growth factor-ß (TGF-β), and its expression is impaired in scleroderma. The roles of adiponectin, a PPAR-γ regulated pleiotropic adipokine, in regulating the response of fibroblasts and in mediating the effects of PPAR-γ are unknown.

Methods
Regulation of fibrotic gene expression and TGF-ß signaling by adiponectin and adenosine monophosphate protein-activated (AMP) kinase agonists were examined in normal fibroblasts in monolayer cultures and in three-dimensional skin equivalents. AdipoR1/2 expression on skin fibroblasts was determined by real-time quantitative PCR.

Results
Adiponectin, an adipokine directly regulated by PPAR-γ, acts as a potent anti-fibrotic signal in normal and scleroderma fibroblasts that abrogates the stimulatory effects of diverse fibrotic stimuli and reduces elevated collagen gene expression in scleroderma fibroblasts. Adiponectin responses are mediated via AMP kinase, a fuel-sensing cellular enzyme that is necessary and sufficient for down-regulation of fibrotic genes by blocking canonical Smad signaling. Moreover, we demonstrate that endogenous adiponectin accounts, at least in part, for the anti-fibrotic effects exerted by ligands of PPAR-γ.

Conclusions
These findings reveal a novel link between cellular energy metabolism and extracellular matrix homeostasis converging on AMP kinase. Since the levels of adiponectin as well as its receptor are impaired in scleroderma patients with progressive fibrosis, the present results suggest a potential role for defective adiponectin expression or function in progressive fibrogenesis in scleroderma and other chronic fibrosing conditions. Restoring the adiponectin signaling axis in fibroblasts might, therefore, represent a novel pharmacological approach to controlling fibrosis.
P2X7 receptor-mediated Nlrp3-inflammasome activation is a genetic determinant of macrophage-dependent crescentic glomerulonephritis
Authors: Deplano Simona , Cook H Terence , Russell Ryan , Franchi Luigi , Schneiter Sabine , Bhangal Gurjeet , Unwin Robert J , Pusey Charles D , Tam Frederick W K , Behmoaras Jacques 
Published: October 2012

Abstract
A novel mechanism in genetically determined P2RX7 levels in macrophages regulates Nlrp3-inflammasome activation and susceptibility to crescentic glomerulonephritis.
P2RX7, a mediator of IL-1β and IL-18 processing and release, is a ligand-gated cation channel that is expressed by macrophages. In experimental Crgn, P2RX7 deficiency attenuates renal injury, but the underlying mechanism is unknown. Here, we show that P2RX7 levels and the expression of several genes belonging to the Nlrp3-inflammasome pathway are up-regulated in the macrophages of the WKY rat, a strain uniquely susceptible to macrophage-dependent NTN. Importantly, following P2RX7 activation, WKY BMDMs produce markedly increased levels of active caspase-1, IL-1β, and IL-18 when compared with the NTN-resistant LEW rat BMDMs. P2RX7 and active IL-1β, IL-18, and caspase-1 protein levels were markedly increased in the WKY nephritic glomeruli 4 days following induction of NTN, and the use of a P2RX7 antagonist reduced the levels of secreted active IL-1β. Interestingly, the post-translational control of P2RX7-mediated inflammasome activation is under the genetic regulation of two previously identified Crgn quantitative trait loci in the BMDMs and nephritic glomeruli of the WKY rat. In conclusion, we propose a novel mechanism, whereby genetically determined P2RX7 levels in macrophages regulate Nlrp3-inflammasome activation and susceptibility to Crgn.
Insights into the role of progranulin in immunity, infection, and inflammation
Authors: Jian Jinlong , Konopka Jessica , Liu Chuanju 
Published: October 2012

AbstractReview on the role of progranulin in immunity, infection, and inflammation, and its therapeutic potential in treating inflammatory conditions.PGRN, a pleiotrophic growth factor, is known to play an important role in the maintenance and regulation of the homeostatic dynamics of normal tissue development, proliferation, regeneration, and the host-defense response and therefore, has been widely studied in the fields of infectious diseases, wound healing, tumorigenesis, and neuroproliferative and degenerative diseases. PGRN has also emerged as a multifaceted immune-regulatory molecule through regulating the signaling pathways known to be critical for immunology, especially TNF/TNFR signaling. In this review, we start with updates about the interplays of PGRN with ECM proteins, proteolytic enzymes, inflammatory cytokines, and cell-surface receptors, as well as various pathophysiological processes involved. We then review the data supporting an emerging role of PGRN in the fields of the “Cubic of I”, namely, immunity, infection, and inflammation, with special focus on its regulation of autoimmune syndromes. We conclude with insights into the immunomodulating, anti-inflammatory, therapeutic potential of PGRN in treating diseases with an inflammatory etiology in a vast range of medical specialties.
New Criteria for Response to Treatment in Immunoglobulin Light Chain Amyloidosis Based on Free Light Chain Measurement and Cardiac Biomarkers: Impact on Survival Outcomes
Authors: Palladini Giovanni , Dispenzieri Angela , Gertz Morie A. , Kumar Shaji , Wechalekar Ashutosh , Hawkins Philip N. , Schönland Stefan , Hegenbart Ute , Comenzo Raymond , Kastritis Efstathios , Dimopoulos Meletios A. , Jaccard Arnaud , Klersy Catherine , Merlini Giampaolo 
Published: October 2012

Purpose To identify the criteria for hematologic and cardiac response to treatment in immunoglobulin light chain (AL) amyloidosis based on survival analysis of a large patient population. Patients and Methods We gathered for analysis 816 patients with AL amyloidosis from seven referral centers in the European Union and the United States. A different cohort of 374 patients prospectively evaluated at the Pavia Amyloidosis Research and Treatment Center was used for validation. Data was available for all patients before and 3 and/or 6 months after initiation of first-line therapy. The prognostic relevance of different criteria for hematologic and cardiac response was assessed. Results There was a strong correlation between the extent of reduction of amyloidogenic free light chains (FLCs) and improvement in survival. This allowed the identification of four levels of response: amyloid complete response (normal FLC ratio and negative serum and urine immunofixation), very good partial response (difference between involved and uninvolved FLCs [dFLC] < 40 mg/L), partial response (dFLC decrease > 50%), and no response. Cardiac involvement is the major determinant of survival, and changes in cardiac function after therapy can be reliably assessed using the cardiac biomarker N-terminal natriuretic peptide type B (NT-proBNP). Changes in FLC and NT-proBNP predicted survival as early as 3 months after treatment initiation. Conclusion This study identifies and validates new criteria for response to first-line treatment in AL amyloidosis, based on their association with survival in large patient populations, and offers surrogate end points for clinical trials.
Risks of Less Common Cancers in Proven Mutation Carriers With Lynch Syndrome
Authors: Engel Christoph , Loeffler Markus , Steinke Verena , Rahner Nils , Holinski-Feder Elke , Dietmaier Wolfgang , Schackert Hans K. , Goergens Heike , von Knebel Doeberitz Magnus , Goecke Timm O. , Schmiegel Wolff , Buettner Reinhard , Moeslein Gabriela , Letteboer Tom G.W. , García Encarna Gómez , Hes Frederik J. , Hoogerbrugge Nicoline , Menko Fred H. , van Os Theo A.M. , Sijmons Rolf H. , Wagner Anja , Kluijt Irma , Propping Peter , Vasen Hans F.A. 
Published: October 2012

Purpose Patients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6. Patients and Methods Data were pooled from the German and Dutch national Lynch syndrome registries. Seven different cancer types were analyzed: stomach, small bowel, urinary bladder, other urothelial, breast, ovarian, and prostate cancer. Age-, sex- and MMR gene–specific cumulative risks (CRs) were calculated using the Kaplan-Meier method. Sex-specific incidence rates were compared with general population incidence rates by calculating standardized incidence ratios (SIRs). Multivariate Cox regression analysis was used to estimate the impact of sex and mutated gene on cancer risk. Results The cohort comprised 2,118 MMR gene mutation carriers (MLH1, n = 806; MSH2, n = 1,004; MSH6, n = 308). All cancers were significantly more frequent than in the general population. The highest risks were found for male small bowel cancer (SIR, 251; 95% CI, 177 to 346; CR at 70 years, 12.0; 95% CI, 5.7 to 18.2). Breast cancer showed an SIR of 1.9 (95% CI, 1.4 to 2.4) and a CR of 14.4 (95% CI, 9.5 to 19.3). MSH2 mutation carriers had a considerably higher risk of developing urothelial cancer than MLH1 or MSH6 carriers. Conclusion The sex- and gene-specific differences of less common cancer risks should be taken into account in cancer surveillance and prevention programs for patients with Lynch syndrome.
Incidence of HIV-Related Anal Cancer Remains Increased Despite Long-Term Combined Antiretroviral Treatment: Results From the French Hospital Database on HIV
Authors: Piketty Christophe , Selinger-Leneman Hana , Bouvier Anne-Marie , Belot Aurelien , Mary-Krause Murielle , Duvivier Claudine , Bonmarchand Manuela , Abramowitz Laurent , Costagliola Dominique , Grabar Sophie 
Published: October 2012

Purpose To study recent trends in the incidence of anal cancer in HIV-infected patients receiving long-term combined antiretroviral treatment (cART) compared with the general population. Patients and Methods From the French Hospital Database on HIV, we identified 263 cases of invasive anal squamous cell carcinoma confirmed histologically between 1992 and 2008. We compared incidence rates of anal cancer across four calendar periods: 1992-1996 (pre-cART period), 1997-2000 (early cART period), and 2001-2004 and 2005-2008 (recent cART periods). Standardized incidence ratios (SIRs) were calculated by using general population incidence data from the French Network of Cancer Registries. Results In HIV-infected patients, the hazard ratio (HR) in the cART periods versus the pre-cART period was 2.5 (95% CI, 1.28 to 4.98). No difference was observed across the cART calendar periods (HR, 0.9; 95% CI, 0.6 to 1.3). In 2005-2008, HIV-infected patients compared with the general population had an excess risk of anal cancer, with SIRs of 109.8 (95% CI, 84.6 to 140.3), 49.2 (95% CI, 33.2 to 70.3), and 13.1 (95% CI, 6.8 to 22.8) for men who have sex with men (MSM), other men, and women, respectively. Among patients with CD4 cell counts above 500/μL for at least 2 years, SIRs were 67.5 (95% CI, 41.2 to 104.3) when the CD4 nadir was less than 200/μL for more than 2 years and 24.5 (95% CI, 17.1 to 34.1) when the CD4 nadir was more than 200/μL. Conclusion Relative to that in the general population, the risk of anal cancer in HIV-infected patients is still extremely high, even in patients with high current CD4 cell counts. cART appears to have no preventive effect on anal cancer, particularly in MSM.
Clinical outcomes of endovascular treatments for critical limb ischemia with chronic total occlusive lesions limited to below-the-knee arteries
Authors: Park Sang Woo , Kim Jun Seok , Yun Ik Jin , Hwang Jae Joon , Lee Song Am , Chee Hyun Keun , Chang Seong-Hwan , Shin Dong Hyeok , Jung Hong Geun , Chang Il Soo 
Published: October 2012

Background Diabetes mellitus tends to have the greatest impact on the smaller vessels and contributes significantly to occlusive disease from the popliteal artery distally. Purpose To evaluate the clinical outcomes after a balloon angioplasty with or without stent placement in diabetic patients with critical limb ischemia (CLI) by chronic total occlusion (CTO) limited to below-the-knee (BTK) arteries. Material and Methods From August 2005, patients who presented CLI and CTO limited to the BTK arteries, and who underwent endovascular treatment, were included in this study. The primary endpoints evaluated were technical success, limb salvage, and primary patency. The secondary endpoints evaluated were 30-day access site, intervention site, and systemic complications. Patency and limb salvage were evaluated using the Kaplan-Meier method and compared using Fisher's exact test. Results The BTK endovascular treatment (EVT) was performed on 64 limbs. Technical success rate was 93.8% and limb salvage rate was 90.6%. Three of four limbs with technical failure and three of 60 limbs with technical success underwent BTK amputation and the comparison of these rates were significantly different (75% vs. 5%, P = 0.002). Primary patency rates for the limbs were 75% and 59.1% at 6-month and 12-month follow-up, respectively. Minor complications disappeared through the follow-up periods and there was no 30-day complication or systemic adverse events for the treated vessel. Conclusion Even though EVT for CLI in patients with diabetes and CTO in isolated BTK arteries does not have comparable primary patency, it can lead to a very high rate of limb salvage. This result can accentuate the importance of more blood flow to the foot by means of successful revascularization using EVT rather than long-term patency in CTO of isolated BTK arteries.
Computed tomography characterization of neuroendocrine tumors of the thymus can aid identification and treatment
Authors: Li Hui , Wang De-ling , Liu Xue-wen , Geng Zhi-jun , Xie Chuan-Miao 
Published: October 2012

Background Neuroendocrine tumors of the thymus are extremely rare anterior mediastinal tumors. The few studies reporting these tumors have focused on the clinical manifestations and do not provide a summary of characteristic computed tomography (CT) findings. Purpose To investigate the CT appearances of neuroendocrine tumors of the thymus in order to improve the diagnostic and resection efficacy. Material and Methods Nine cases of pathologically identified thymic neuroendocrine tumors were retrospectively analyzed by CT. All the patients underwent non-enhanced and contrast-enhanced CT. Multiple CT features were examined, including tumor location, shape, margins, CT attenuation, involvement of surrounding structures, and distant metastasis. Results A total of nine masses were examined in this study. The maximum tumor diameter ranged from 5 to 14 cm (average, 9 cm). The shapes of six masses were lobulated and three were rounded or oval and the margins of seven masses were unclear while two masses were sharp. All the masses showed hypodensity or isodensity compared to muscles in the anterior thoracic wall on non-enhanced CT images. Two masses showed homogeneous attenuation by non-enhanced CT imaging and moderate homogeneous enhancement after contrast administration, while seven masses showed heterogeneous attenuation with patchy low-attenuation foci and showed moderate to strong heterogeneous enhancement. Involvement of adjacent structures was observed in six cases. Five cases were observed to have lymph node metastases and four cases had distant metastases. Conclusion Neuroendocrine tumors of the thymus are rare tumors of the anterior mediastinum with a number of distinct CT characteristics. Most importantly, the density of the tumors was heterogeneous with necrosis or cystic degeneration and moderately or strongly enhancement after bolus injection of contrast medium, which may allow for more efficient tumor identification. Thus, CT can improve of the diagnosis of neuroendocrine tumors and provide critical information for surgical planning.
Neonatal screening for congenital hypothyroidism in East Azerbaijan, Iran: the first report
Authors: Zeinalzadeh Ali Hossein , Talebi Malihe 
Published: October 2012

Objectives To investigate the prevalence of congenital hypothyroidism (CH) among neonates in East Azerbaijan, Iran. Methods A cross-sectional study conducted from 2009 to 2010. Most heel blood samples were taken between three and seven days of birth. Thyroid stimulating hormone (TSH) was tested using the enzyme-linked immunosorbent assay method. Neonates with abnormal screening results (TSH>20 mIU/L, T4<6.5 mg/dL) were re-examined. Data were analysed using SPSS software. Results A total of 62,459 infants were screened. Of 1562 re-called subjects (re-call rate 2.5%), 94 cases with CH were detected, yielding a CH prevalence of 1:666 (female:male ratio 1:1.4). Conclusion The prevalence of CH in East Azerbaijan province is higher in comparison with worldwide levels. These results emphasize the importance of the neonatal screening programme.
Sociocultural challenges of beta-thalassaemia major birth in carriers of beta-thalassaemia in Iran
Authors: Haghpanah Sezaneh , Nasirabadi Shiva , Rahimi Nazila , Faramarzi Hossein , Karimi Mehran 
Published: October 2012

Objective Despite premarital screening, prenatal diagnosis and the option for voluntary termination of pregnancy, some Iranian couples continue a pregnancy with a fetus affected with beta-thalassaemia major (β-TM). We examined the reasons for this decision, to evaluate the sociocultural challenges these couples face. Methods A retrospective evaluation of medical records of all fetuses aborted was conducted to identify those with β-TM, to determine the frequency of β-TM births and to establish the number of couples with β-thalassaemia who declined prenatal diagnosis or a termination of pregnancy in this period. We investigated the reasons for declining these options. Results The birth prevalence of β-TM decreased from 39.38 to 2.68 in 100,000 live births from 2005 to 2010. Terminations of pregnancy for affected fetuses increased from 67 in 2005 to 135 in 2010. We identified eight couples as β-thalassaemia carriers who declined prenatal diagnosis or a termination of pregnancy. All but one couple already had a child with β-TM. The reasons for declining prenatal diagnosis were strong religious beliefs, superstition and faith in a supernatural solution in six couples. Economic and cultural factors, and previous termination of pregnancy were also mentioned as reasons by the other two couples. Conclusion Although most of the couples had a β-TM child and related socioeconomic problems, their reasons for refusing prenatal diagnosis or termination remain a challenge for the healthcare system in Iran. Couple screening and educational programmes have effectively decreased the rates of refusal in at-risk couples in recent years.
Constraints in the Demand for Education: What Can we Learn from Subjective Assessments?
Authors: Sorokina Olga V. 
Published: October 2012

Abstract
While the large disparities in educational attainment by socioeconomic status in the United States point towards the importance of credit constraints, there is no consensus in the economic literature regarding their pervasiveness. To evaluate how subjective information can enhance our understanding of the role of credit constraints in education, I focus on NLSY79 respondents' assessments of financial obstacles to schooling. About 12 percent of young adults in the data expect to underinvest in education because of financial reasons or the need to work. Using this information in a regression model of educational attainment shows that it provides valuable behavioral insights, above and beyond standard measures of income and family background.
From a 'Liberal' to a 'Social democratic' welfare state: the translation of the English Compact into a Swedish context
Authors: Johansson Håkan , Johansson Mairon 
Published: October 2012

AbstractEngland was one of the first countries to install a Compact to regulate the relationship between state and civil society and since then several other countries have followed and initiated national Agreements, Charters or Concordats. Despite a growing academic interest into such national Compact models we have insufficient knowledge of how such ideas ‘from abroad’ are adapted and molded to fit with ‘domestic’ legacies, institutions and power disparities. The purpose of this article is to analyze the translation of the English Compact into a Swedish context and above all how domestic Civil Society Organizations (CSOs) acted to adjust such an international model to a national context. The article draws upon studies of written documents and interviews with key actors (politicians and CSO representatives) and two main conclusions are being presented. First, the article demonstrates that CSOs played an important role as translation agents as they identified the Compact idea long before key decision makers did, yet that the complete translation of the Compact model into a Swedish context was dependent upon the political will and ownership of central decision-makers. Second, the article demonstrates that the translation process was not as ordered as sometimes depicted within the translation literature and instead chains of translation processes was detected. These findings address a need to open up the translation perspective for the analysis of multiple types of translation agents and to understand translation as a nested process, in which one translation process might very well be interrelated with other parallel translation processes.
Policy Tools or Mirrors of Politics. Government-Voluntary Sector Compacts in the Post-Welfare State Age
Authors: Reuter Marta , Wijkström Filip , von Essen Johan 
Published: October 2012

AbstractGovernment-voluntary sector “compacts” have emerged in the recent years as an innovative nonprofit policy practice in many industrialized countries around the world. Originating in England in the late 1990s, the compact phenomenon has today spread to societies with relatively different tracks of inter-sectorial relations and different civil society regimes. This introductory article seeks to chart out the diverse functions that the compact solution seems to perform in different institutional surroundings, and it also opens up for a comparative discussion of the broader socio-political contexts in which this policy instrument has developed.
Multistep degradation method for β-O-4 linkage in lignins: γ-TTSA method. Part 2: reaction of lignin model polymer (DHP)
Authors: Ando Daisuke , Nakatsubo Fumiaki , Takano Toshiyuki , Nishimura Hiroshi , Katahira Masato , Yano Hiroyuki 
Published: October 2012

Abstract
A selective cleavage method for β-O-4 linkages (the γ-TTSA method) was introduced in previous works, which consists of four reaction steps: (1) γ-tosylation, (2) thioetherification, (3) sulfonylation, and (4) mild alkali degradation. This method was applied to the degradation of a lignin polymer model (dehydrogenation polymer, DHP) consisting of guaiacyl units. Each reaction step was followed by Fourier transform infrared (FT-IR) spectroscopy and heteronuclear single quantum coherence nuclear magnetic resonance (HSQC-NMR) spectroscopy. It was demonstrated that only the β-O-4 linkage was selectively cleaved by the γ-TTSA method, although other linkages, such as β-5 and β-β linkages, were also present in the DHP. Consequently, the γ-TTSA method is expected to be also useful for the degradation of native lignins.