bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Plasma and Urine Neutrophil Gelatinase Associated Lipocalin (NGAL) and Cystatin C in Early Diagnosis of Septic Acute Kidney Injury in Critically Ill Patients
Authors: Aydoğdu Müge , Gürsel Gül , Sancak Banu , Yeni Serpil , Sarı Gülçin , Taşyürek Seçil , Türk Murat , Yüksel Seher , Senes Mehmet , Özis Türkan Nadir 
Published: June 2013

Aim: To assess and compare the roles of plasma and urine concentrations of neutrophil gelatinase associated lipocalin (NGAL) and Cystatin C for early diagnosis of septic acute kidney injury (AKI) in adult critically ill patients.Methods: Patients were divided into three groups as sepsis-non AKI, sepsis-AKI and non sepsis-non AKI. Plasma samples for NGAL and Cystatin C were determined on admission and on alternate days and urinary samples were collected for every day until ICU discharge.Results: One hundred fifty one patients were studied; 66 in sepsis-non AKI, 63 in sepsis-AKI, 22 in non-sepsis-non-AKI groups. Although plasma NGAL performed less well (AUC 0.44), urinary NGAL showed significant discrimination for AKI diagnosis (AUC 0.80) with a threshold value of 29.5 ng/ml (88% sensitivity, 73% specificity). Both plasma and urine Cystatin C worked well for the diagnosis of AKI (AUC 0.82 and 0.86, thresholds 1.5 and 0.106 mg/L respectively).Conclusion: Plasma and urinary Cystatin C and urinary NGAL are useful markers in predicting AKI in septic critically ill patients. Plasma NGAL raises in patients with sepsis in the absence of AKI and should be used with caution as a marker of AKI in septic ICU patients.
Diagnostic Use of Serum Ferritin Levels to Differentiate Infectious and Noninfectious Diseases in Patients with Fever of Unknown Origin
Authors: Kim Seong Eun , Kim Uh Jin , Jang Mi Ok , Kang Seung Ji , Jang Hee Chang , Jung Sook In , Lee Shin Seok , Park Kyung Hwa 
Published: June 2013

INTRODUCTION: In this study, we determined whether serum ferritin levels could be used to differentiate between fever of unknown origin (FUO) caused by infectious and noninfectious diseases.METHODS: FUO patients were hospitalized at Chonnam National University Hospital between January, 2005 and December, 2011. According to the final diagnoses, five causes were identified, including infectious diseases, hematologic diseases, noninfectious inflammatory diseases, miscellaneous and undiagnosed.RESULTS: Of the 77 patients, 11 were caused by infectious diseases, 13 by hematologic diseases, 20 by noninfectious inflammatory diseases, 8 by miscellaneous diseases, and 25 were undiagnosed. The median serum ferritin levels in infectious diseases was lower than those in hematologic diseases and (median (interquartile range) of 282.4 (149.0–951.8) ng/mL for the infectious disease group, 1818.2 (485.4–4789.5) ng/mL for the hematologic disease group, and 563.7 (399.6–1927.2) ng/mL for the noninfectious inflammatory disease group,p= 0.048, Kruskal–Wallis test). By comparison using the Mann–Whitney test, statistically significant differences were found only between the infectious disease and hematologic disease groups (p= 0.049) and between the infectious disease and groups (p= 0.04).CONCLUSION: An optimal cutoff value of serum ferritin levels to predict FUO caused by a noninfectious disease (hematologic diseases, noninfectious inflammatory diseases) was established as 561 ng/mL.
First-in-Human Phase I Dose-Escalation Study of the HSP90 Inhibitor AUY922 in Patients with Advanced Solid Tumors
Authors: Sessa Cristiana , Shapiro Geoffrey I. , Bhalla Kapil N. , Britten Carolyn , Jacks Karen S. , Mita Monica , Papadimitrakopoulou Vali , Pluard Tim , Samuel Thomas A. , Akimov Mikhail , Quadt Cornelia , Fernandez-Ibarra Cristina , Lu Hong , Bailey Stuart , Chica Sandra , Banerji Udai 
Published: June 2013

Abstract
Purpose: A phase I study was conducted with the primary objective of determining the maximum tolerated dose (MTD) of AUY922 in patients with advanced solid tumors. Secondary objectives included characterization of the safety, pharmacokinetic, and pharmacodynamic profiles.
Patients and Methods: Patients with advanced solid tumors received 1-hour i.v. infusions of AUY922 once a week in a 28-day cycle. An adaptive Bayesian logistic regression model that employed observed dose-limiting toxicities (DLT) in the first treatment cycle was used to guide dose-escalation decisions, with the established MTD to be used in phase II studies.
Results: One hundred and one patients were enrolled and explored at doses in the range of 2 to 70 mg/m2. DLTs occurred in 8 patients (22–70 mg/m2) and included diarrhea, asthenia/fatigue, anorexia, atrial flutter, and visual symptoms. At 70 mg/m2, the AUY922 concentration achieved was consistent with active concentrations in a range of xenograft models. There was evidence of target inhibition in peripheral blood mononuclear cells (HSP70 induction) and tumor (client protein depletion and reduction of metabolic activity by 18F-FDG PET). The recommended phase II dose (RP2D) of 70 mg/m2 was proposed on the basis of toxicity and pharmacokinetic and pharmacodynamic profiles.
Conclusions: At the RP2D of 70 mg/m2, AUY922 exhibited acceptable tolerability, and phase II single-agent and combination studies have been initiated in patients with HER2-positive breast, gastric, and non–small cell lung cancers. Clin Cancer Res; 19(13); 3671–80. ©2013 AACR.
Phase I Trial of a New Schedule of Romidepsin in Patients with Advanced Cancers
Authors: Amiri-Kordestani Laleh , Luchenko Victoria , Peer Cody J. , Ghafourian Kambiz , Reynolds James , Draper Deb , Frye Robin , Woo Sue , Venzon David , Wright John , Skarulis Monica , Figg William D. , Fojo Tito , Bates Susan E. , Piekarz Richard L. 
Published: June 2013

Abstract
Purpose: Romidepsin is a potent histone deacetylase inhibitor (HDI) with activity in T-cell lymphoma. Given preclinical data showing greater induction of gene expression with longer exposures to HDIs, a phase I study of a day 1, 3, and 5 romidepsin schedule was evaluated. A secondary objective was to assess the effect of romidepsin on radioactive iodine (RAI) uptake in thyroid cancers.
Experimental Design: Open-label, single-arm, phase I, 3 + 3 dose escalation study. Romidepsin was administered as a 4-hour infusion on days 1, 3, and 5 of a 21-day cycle. Pharmacokinetics (PK) and pharmacodynamics (PD) were assessed, including histone acetylation in peripheral blood mononuclear cells (PBMC), RAI uptake in refractory thyroid cancer, and HDI-related ECG changes.
Results: Twenty-eight patients with solid tumors, including 11 patients with thyroid cancer were enrolled. Six dose levels were explored, and 7 mg/m2 on days 1, 3, and 5 was identified as tolerable. No Response Evaluation Criteria In Solid Tumors–defined objective responses were recorded although 9 patients had stable disease a median 30 weeks (range, 21–112) including 6 with thyroid cancer a median of 33 weeks. PD studies detected acetylated histones in PBMCs and ECG changes beginning at low dose levels. Follow-up RAI scans in patients with RAI refractory thyroid cancer did not detect meaningful increases.
Conclusions: A romidepsin dose of 7 mg/m2 administered on days 1, 3, and 5 was found tolerable and resulted in histone acetylation in PBMCs. Although there were no objective responses with romidepsin alone, this schedule may be useful for developing combination studies in solid tumors. Clin Cancer Res; 19(16); 4499–507. ©2013 AACR.
Breast Cancer Index Identifies Early-Stage Estrogen Receptor–Positive Breast Cancer Patients at Risk for Early- and Late-Distant Recurrence
Authors: Zhang Yi , Schnabel Catherine A. , Schroeder Brock E. , Jerevall Piiha-Lotta , Jankowitz Rachel C. , Fornander Tommy , Stål Olle , Brufsky Adam M. , Sgroi Dennis , Erlander Mark G. 
Published: June 2013

Abstract
Purpose: Residual risk of relapse remains a substantial concern for patients with hormone receptor–positive breast cancer, with approximately half of all disease recurrences occurring after five years of adjuvant antiestrogen therapy.
Experimental Design: The objective of this study was to examine the prognostic performance of an optimized model of Breast Cancer Index (BCI), an algorithmic gene expression–based signature, for prediction of early (0–5 years) and late (&gt;5 years) risk of distant recurrence in patients with estrogen receptor–positive (ER+), lymph node–negative (LN−) tumors. The BCI model was validated by retrospective analyses of tumor samples from tamoxifen-treated patients from a randomized prospective trial (Stockholm TAM, n = 317) and a multi-institutional cohort (n = 358).
Results: Within the Stockholm TAM cohort, BCI risk groups stratified the majority (∼65%) of patients as low risk with less than 3% distant recurrence rate for 0 to 5 years and 5 to 10 years. In the multi-institutional cohort, which had larger tumors, 55% of patients were classified as BCI low risk with less than 5% distant recurrence rate for 0 to 5 years and 5 to 10 years. For both cohorts, continuous BCI was the most significant prognostic factor beyond standard clinicopathologic factors for 0 to 5 years and more than five years.
Conclusions: The prognostic sustainability of BCI to assess early- and late-distant recurrence risk at diagnosis has clinical use for decisions of chemotherapy at diagnosis and for decisions for extended adjuvant endocrine therapy beyond five years. Clin Cancer Res; 19(15); 4196–205. ©2013 AACR.
Single-Domain Antibody–Based and Linker-Free Bispecific Antibodies Targeting FcγRIII Induce Potent Antitumor Activity without Recruiting Regulatory T Cells
Authors: Rozan Caroline , Cornillon Amélie , Pétiard Corinne , Chartier Martine , Behar Ghislaine , Boix Charlotte , Kerfelec Brigitte , Robert Bruno , Pèlegrin André , Chames Patrick , Teillaud Jean-Luc , Baty Daniel 
Published: June 2013

Abstract
Antibody-dependent cell-mediated cytotoxicity, one of the most prominent modes of action of antitumor antibodies, suffers from important limitations due to the need for optimal interactions with Fcγ receptors. In this work, we report the design of a new bispecific antibody format, compact and linker-free, based on the use of llama single-domain antibodies that are capable of circumventing most of these limitations. This bispecific antibody format was created by fusing single-domain antibodies directed against the carcinoembryonic antigen and the activating FcγRIIIa receptor to human Cκ and CH1 immunoglobulin G1 domains, acting as a natural dimerization motif. In vitro and in vivo characterization of these Fab-like bispecific molecules revealed favorable features for further development as a therapeutic molecule. They are easy to produce in Escherichia coli, very stable, and elicit potent lysis of tumor cells by human natural killer cells at picomolar concentrations. Unlike conventional antibodies, they do not engage inhibitory FcγRIIb receptor, do not compete with serum immunoglobulins G for receptor binding, and their cytotoxic activity is independent of Fc glycosylation and FcγRIIIa polymorphism. As opposed to anti-CD3 bispecific antitumor antibodies, they do not engage regulatory T cells as these latter cells do not express FcγRIII. Studies in nonobese diabetic/severe combined immunodeficient gamma mice xenografted with carcinoembryonic antigen–positive tumor cells showed that Fab-like bispecific molecules in the presence of human peripheral blood mononuclear cells significantly slow down tumor growth. This new compact, linker-free bispecific antibody format offers a promising approach for optimizing antibody-based therapies. Mol Cancer Ther; 12(8); 1481–91. ©2013 AACR.
Antitumor Impact ofp14ARFon Gefitinib-Resistant Non–Small Cell Lung Cancers
Authors: Saito Ken , Takigawa Nagio , Ohtani Naoko , Iioka Hidekazu , Tomita Yuki , Ueda Ryuzo , Fukuoka Junya , Kuwahara Kazuhiko , Ichihara Eiki , Kiura Katsuyuki , Kondo Eisaku 
Published: June 2013

AbstractActivation of the epidermal growth factor receptor (EGFR) has been observed in many malignant tumors and its constitutive signal transduction facilitates the proliferation of tumors. EGFR-tyrosine kinase inhibitors, such as gefitinib, are widely used as a molecular-targeting agent for the inactivation of EGFR signaling and show considerable therapeutic effect in non–small cell lung cancers harboring activating EGFR mutations. However, prolonged treatment inevitably produces tumors with additional gefitinib-resistant mutations in EGFR, which is a critical issue for current therapeutics. We aimed to characterize the distinct molecular response to gefitinib between the drug-resistant and drug-sensitive lung adenocarcinoma cells in order to learn about therapeutics based on the molecular information. From the quantitative PCR analysis, we found a specific increase in p14ARF expression in gefitinib-sensitive lung adenocarcinoma clones, which was absent in gefitinib-resistant clones. Moreover, mitochondria-targeted p14ARF triggered the most augmented apoptosis in both clones. We identified the amino acid residues spanning from 38 to 65 as a functional core of mitochondrial p14ARF (p14 38-65 a.a.), which reduced the mitochondrial membrane potential and caused caspase-9 activation. The synthesized peptide covering the p14 38-65 a.a. induced growth suppression of the gefitinib-resistant clones without affecting nonneoplastic cells. Notably, transduction of the minimized dose of the p14 38-65 peptide restored the response to gefitinib like that in the sensitive clones. These findings suggest that the region of p14ARF 38-65 a.a. is critical in the pharmacologic action of gefitinib against EGFR-mutated lung adenocarcinoma cells and has potential utility in the therapeutics of gefitinib-resistant cancers. Mol Cancer Ther; 12(8); 1616–28. ©2013 AACR.
Thrombosis in central obesity and metabolic syndrome: Mechanisms and epidemiology
Authors: Morange Pierre-Emmanuel , Alessi Marie-Christine 
Published: June 2013

summaryCentral obesity is a key feature of the metabolic syndrome (metS), a multiplex risk factor for subsequent development of type 2 diabetes and cardiovascular disease. Many metabolic alterations closely related to this condition exert effects on platelets and vascular cells. A procoagulant and hypofibrinolytic state has been identified, mainly underlain by inflammation, oxidative stress, dyslipidaemia, and ectopic fat that accompany central obesity. In support of these data, central obesity independently predisposes not only to atherothrombosis but also to venous thrombosis.
Characteristics and Outcomes of Patients Receiving New and Replacement Implantable Cardioverter-Defibrillators
Authors: Kramer Daniel B. , Kennedy Kevin F. , Noseworthy Peter A. , Buxton Alfred E. , Josephson Mark E. , Normand Sharon-Lise , Spertus John A. , Zimetbaum Peter J. , Reynolds Matthew R. , Mitchell Susan L. 
Published: June 2013

Background—
Little is known about the clinical features, procedural risks, or survival of patients receiving replacement versus new implantable cardioverter-defibrillators (ICDs).

Methods and Results—

Entries in the National Cardiovascular Data Registry (NCDR) ICD Registry from 2005 through 2010 were eligible for inclusion (n=463 978). Baseline demographic data, clinical information, and procedural variables were compared between patients receiving new (n=359 993; 77.6%) and replacement (n=103 985; 22.4%) ICDs and entered into a propensity match model to determine adjusted survival rates. Patients receiving replacement ICDs were older (70.7 versus 67.5 years of age) and more likely to have atrial fibrillation (41.8% versus 31.4%;
P
<0.001) and ventricular tachycardia (60.5% versus 33.9%;
P
<0.001) compared with patients receiving new ICDs. Median battery life was only 4.6 years (25%–75% interquartile range, 3.7–5.8) for all replaced devices, 5.8 (25%–75% interquartile range, 4.2–7.5) for single-chamber, 5.1 (25%–75% interquartile range, 4.1–6.1) for dual-chamber, and 3.9 (25%–75% interquartile range, 3.2–4.6) years for biventricular devices. Patients receiving replacement ICDs had lower rates of index admission complications (0.9% versus 3.2%;
P
<0.001) but greater risk for death compared receiving patients receiving new ICDs in unadjusted analysis (hazard ratio, 1.18; 95% confidence interval, 1.16–1.20;
P
<0.0001) and after propensity-score matching (hazard ratio, 1.28; 95% confidence interval, 1.25–1.30;
P
<0.0001).

Conclusions—
Patients receiving replacement ICDs are older and at greater risk for death compared with those receiving initial ICD implants. The battery life of initial ICDs is shorter than previously reported.
Divide and Rule in Bahrain and the Elusive Pursuit for a United Front: The Experience of the Constitutive Committee and the 1972 Uprising
Authors: AlShehabi Omar Hesham 
Published: June 2013

Abstract
This article focuses on the ‘The Constitutive Committee’, the 1971–2 mass-movement to create a general trade union in Bahrain. The first mass-movement after independence, it was also the country’s first public non-sectarian organised movement. Initially a joint effort between ‘The Popular Front’ and the ‘National Liberation Front’, it represented the first formal collaboration between the two major factions of the Left, which had historically entertained an ambivalent relationship. This article traces the committee’s establishment and development, culminating with the ‘March 1972 uprising’. The article places the Constitutive Committee within a historical narrative that begins with the Higher Executive Committee movement of 1954–6 and leads up to the February 2011 Arab uprisings. The framework emphasises the dialectical struggles of popular movements searching for a united front for political change, faced by a regime that has mastered the use of divide and rule to entrench social and political fragmentation.
The Limits of Sociological Marxism?
Authors: Morton Adam David 
Published: June 2013

AbstractWithin the agenda of historical-materialist theory and practice Sociological Marxism has delivered a compelling perspective on how to explore and link the analysis of civil society, the state, and the economy within an explicit focus on class exploitation, emancipation, and rich ethnography. This article situates a major analysis of state formation, the rise of the Justice and Development Party (AKP), and the growth of a broader Islamist movement in Turkey within the main current of Sociological Marxism. It does so in order to critically examine the rather bold revision of the theory of hegemony at the heart of Cihan Tuğal’sPassive Revolution: Absorbing the Islamic Challenge to Capitalism, which posits the separate interaction of political society, civil society and the state in theorising hegemonic politics in Turkey. My contention is that the revision of hegemony that this analysis offers and its state-theoretical commitments are deeply problematic due to the reliance on what I term ‘ontological exteriority’, meaning the treatment of state, civil society and the economy as always-alreadyseparatespheres. The focus of the critique then moves toward highlighting a frustrating lack of direct engagement with Antonio Gramsci’s writings in this disquisition on hegemony and passive revolution, which has important political consequences. While praise for certain aspects of ethnographic and spatial analysis is raised, it is argued that any account of the reordering of hegemony and the restructuring of spatial-temporal contexts of capital accumulation through conditions of passive revolution also needs to draw from a more sophisticated state theory, a direct reading of Gramsci, and broader scalar analysis of spatial relations and uneven development under capitalism.
A 6-yr Climatology of Fronts Affecting Helsinki, Finland, and Their Boundary Layer Structure
Authors: Sinclair Victoria A. 
Published: June 2013

AbstractA 6-yr climatology of the frequency, characteristics, and boundary layer structure of synoptic-scale fronts in Helsinki, Finland, was created using significant weather charts and observations from a 327-m-tall mast and from the Station for Measuring Ecosystem–Atmosphere Relationships III. In total, 855 fronts (332 cold fronts, 236 warm fronts, and 287 occluded fronts) affected Helsinki during the 6-yr period, equating to one front every 2.6 days. Seasonal and diurnal cycles were observed, with frontal frequency peaking during the cold season and during daytime. Composites of warm and cold fronts were developed to provide observationally based conceptual models of the low-level structure of fronts at the end of the North Atlantic Ocean storm track. The composite warm front displays a temperature increase of 4.0°C; a broad, forward-tilting frontal zone; and prolonged, weak-to-moderate precipitation. The composite cold front is characterized by a temperature decrease of 4.4°C, a narrow and slightly rearward-tilting frontal zone, and moderate precipitation collocated with the surface front. Relationships between frontal characteristics and the direction from which fronts approached, the season, time of day, prefrontal boundary layer lapse rate, and the location of the wind shift relative to the thermal gradient were investigated. The prefrontal lapse rate was the single most important variable in determining the temperature change, the height of the maximum temperature change, and the near-surface tilt of both warm and cold fronts. This result demonstrates the interaction between boundary layer and synoptic-scale processes that must be captured by numerical weather prediction models to accurately forecast surface fronts.
Weakening of the Kuroshio Intrusion into the South China Sea over the Past Two Decades
Authors: Nan Feng , Xue Huijie , Chai Fei , Wang Dongxiao , Yu Fei , Shi Maochong , Guo Peifang , Xiu Peng 
Published: June 2013

Abstract
Inferred from the satellite and in situ hydrographic data from the 1990s and 2000s, the Kuroshio intrusion into the South China Sea (SCS) had a weakening trend over the past two decades. Associated with the weakened Kuroshio intrusion, the Kuroshio loop and eddy activity southwest of Taiwan became weaker, whereas the water above the salinity minimum became less saline in the northern SCS. The sea surface height southwest of Taiwan increased at a slower rate compared to other regions of the SCS because of the weakened Kuroshio intrusion. Simulations using the Regional Ocean Modeling System (ROMS) Pacific model show that the strength of the Kuroshio intrusion into the SCS decreased from 1993 to 2010 with a negative trend, −0.24 sverdrups (Sv) yr−1 (1 Sv ≡ 106 m3 s−1), in the total Luzon Strait transport (LST). Although wind-induced Ekman transport through the Luzon Strait became weaker, the magnitude at 0.001 Sv yr−1 was too small to compensate for the negative trend of the LST. On the other hand, the piling up of the water induced by monsoon winds was an important mechanism for changing the pressure gradient across the Luzon Strait and eventually affecting the LST. The sea level gradient between the western Pacific and the SCS had a negative trend, −0.10 cm yr−1, corresponding to a negative trend in the geostrophic transport at −0.20 Sv yr−1. The Kuroshio transport east of Luzon Island also had a negative trend, which might also be linked to the weakening Kuroshio intrusion.