bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human monocytes and macrophages differ in their mechanisms of adaptation to hypoxia
Authors: Fangradt Monique , Hahne Martin , Gaber Timo , Strehl Cindy , Rauch Roman , Hoff Paula , Löhning Max , Burmester Gerd-Rüdiger , Buttgereit Frank 
Published: August 2012

Abstract
Introduction
Inflammatory arthritis is a progressive disease with chronic inflammation of joints, which is mainly characterized by the infiltration of immune cells and synovial hyperproliferation. Monocytes migrate towards inflamed areas and differentiate into macrophages. In inflamed tissues, much lower oxygen levels (hypoxia) are present in comparison to the peripheral blood. Hence, a metabolic adaptation process must take place. Other studies suggest that Hypoxia Inducible Factor 1-alpha (HIF-1α) may regulate this process, but the mechanism involved for human monocytes is not yet clear. To address this issue, we analyzed the expression and function of HIF-1α in monocytes and macrophages, but also considered alternative pathways involving nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFκB).

Methods
Isolated human CD14+ monocytes were incubated under normoxia and hypoxia conditions with or without phorbol 12-myristate 13-acetate (PMA) stimulation, respectively. Nuclear and cytosolic fractions were prepared in order to detect HIF-1α and NFκB by immunoblot. For the experiments with macrophages, primary human monocytes were differentiated into human monocyte derived macrophages (hMDM) using human macrophage colony-stimulating factor (hM-CSF). The effects of normoxia and hypoxia on gene expression were compared between monocytes and hMDMs using quantitative PCR (quantitative polymerase chain reaction).

Results
We demonstrate, using primary human monocytes and hMDM, that the localization of transcription factor HIF-1α during the differentiation process is shifted from the cytosol (in monocytes) into the nucleus (in macrophages), apparently as an adaptation to a low oxygen environment. For this localization change, protein kinase C alpha/beta 1 (PKC-α/β1 ) plays an important role. In monocytes, it is NFκB1, and not HIF-1α, which is of central importance for the expression of hypoxia-adjusted genes.

Conclusions
These data demonstrate that during differentiation of monocytes into macrophages, crucial cellular adaptation mechanisms are decisively changed.
Endotoxemia and mortality prediction in ICU and other settings: underlying risk and co-detection of gram negative bacteremia are confounders
Authors: Hurley James C , Guidet Bertrand , Offenstadt Georges , Maury Eric 
Published: August 2012

Abstract
Introduction
The interdependence between endotoxemia, gram negative (GN) bacteremia and mortality has been extensively studied. Underlying patient risk and GN bacteremia types are possible confounders of the relationship.

Methods
Published studies with ≥10 patients in either ICU or non-ICU settings, endotoxemia detection by limulus assay, reporting mortality proportions and ≥1 GN bacteremia were included. Summary odds ratios (OR) for mortality were derived across all studies by meta-analysis for the following contrasts: sub-groups with either endotoxemia (group three), GN bacteremia (group two) or both (group one) each versus the group with neither detected (group four; reference group). The mortality proportion for group four is the proxy measure of study level risk within L'Abbé plots.

Results
Thirty-five studies were found. Among nine studies in an ICU setting, the OR for mortality was borderline (OR <2) or non-significantly increased for groups two (GN bacteremia alone) and three (endotoxemia alone) and patient group one (GN bacteremia and endotoxemia co-detected) each versus patient group four (neither endotoxemia nor GN bacteremia detected). The ORs were markedly higher for group one versus group four (OR 6.9; 95% confidence interval (CI), 4.4 -to 11.0 when derived from non-ICU studies. The distributions of Pseudomonas aeruginosa and Escherichia coli bacteremias among groups one versus two are significantly unequal.

Conclusions
The co-detection of GN bacteremia and endotoxemia is predictive of increased mortality risk versus the detection of neither but only in studies undertaken in a non-ICU setting. Variation in GN bacteremia species types and underlying risk are likely unrecognized confounders in the individual studies.
Analysis of CLIP and iCLIP methods for nucleotide-resolution studies of protein-RNA interactions
Authors: Sugimoto Yoichiro , König Julian , Hussain Shobbir , Zupan Blaž , Curk Tomaž , Frye Michaela , Ule Jernej 
Published: August 2012

AbstractUV cross-linking and immunoprecipitation (CLIP) and individual-nucleotide resolution CLIP (iCLIP) are methods to study protein-RNA interactions in untreated cells and tissues. Here, we analyzed six published and two novel data sets to confirm that both methods identify protein-RNA cross-link sites, and to identify a slight uridine preference of UV-C-induced cross-linking. Comparing Nova CLIP and iCLIP data revealed that cDNA deletions have a preference for TTT motifs, whereas iCLIP cDNA truncations are more likely to identify clusters of YCAY motifs as the primary Nova binding sites. In conclusion, we demonstrate how each method impacts the analysis of protein-RNA binding specificity.
Clinicopathologic Characteristics of Angioimmunoblastic T-Cell Lymphoma: Analysis of the International Peripheral T-Cell Lymphoma Project
Authors: Federico Massimo , Rudiger Thomas , Bellei Monica , Nathwani Bharat N. , Luminari Stefano , Coiffier Bertrand , Harris Nancy L. , Jaffe Elaine S. , Pileri Stefano A. , Savage Kerry J. , Weisenburger Dennis D. , Armitage James O. , Mounier Nicholas , Vose Julie M. 
Published: August 2012

PurposeThe International Peripheral T-Cell Lymphoma Project was undertaken to better understand the subtypes of T-cell and natural killer (NK) –cell lymphomas.Patients and MethodsAngioimmunoblastic T-cell lymphoma (AITL) was diagnosed according to the 2001 WHO criteria by a central review process consisting of panels of expert hematopathologists. Clinical, pathologic, immunophenotyping, treatment, and survival data were correlated.ResultsOf 1,314 patients, 243 (18.5%) were diagnosed with AITL. At presentation, generalized lymphadenopathy was noted in 76% of patients, and 89% had stages III to IV disease. Skin rash was observed in 21% of patients. Hemolytic anemia and hypergammoglobulinemia occurred in 13% and 30% of patients, respectively. Five-year overall and failure-free survivals were 33% and 18%, respectively. At presentation, prognostic models were evaluated, including the standard International Prognostic Index, which comprised the following factors: age ≥ 60 years, stages III to IV disease, lactic dehydrogenase (LDH) > normal, extranodal sites (ENSs) > one, and performance status (PS) ≥ 2; the Prognostic Index for Peripheral T-Cell Lymphoma, comprising: age ≥ 60 years, PS ≥ 2, LDH > normal, and bone marrow involvement; and the alternative Prognostic Index for AITL (PIAI), comprising: age > 60 years, PS ≥ 2, ENSs > one, B symptoms, and platelet count < 150 × 109/L. The simplified PIAI had a low-risk group (zero to one factors), with 5-year survival of 44%, and a high-risk group (two to five factors), with 5-year survival of 24% (P = .0065).ConclusionAITL is a rare clinicopathologic entity characterized by an aggressive course and dismal outcome with current therapies.
Bendamustine in Combination With Rituximab for Previously Untreated Patients With Chronic Lymphocytic Leukemia: A Multicenter Phase II Trial of the German Chronic Lymphocytic Leukemia Study Group
Authors: Fischer Kirsten , Cramer Paula , Busch Raymonde , Böttcher Sebastian , Bahlo Jasmin , Schubert Jöerg , Pflüger Karl H. , Schott Silke , Goede Valentin , Isfort Susanne , von Tresckow Julia , Fink Anna-Maria , Bühler Andreas , Winkler Dirk , Kreuzer Karl-Anton , Staib Peter , Ritgen Matthias , Kneba Michael , Döhner Hartmut , Eichhorst Barbara F. , Hallek Michael , Stilgenbauer Stephan , Wendtner Clemens-Martin 
Published: August 2012

Purpose We investigated the safety and efficacy of bendamustine and rituximab (BR) in previously untreated patients with chronic lymphocytic leukemia (CLL). Patients and Methods In all, 117 patients, age 34 to 78 years, 46.2% of patients at Binet stage C, and 25.6% of patients age 70 years or older received BR chemoimmunotherapy for first-line treatment of CLL. Bendamustine was administered at a dose of 90 mg/m2 on days 1 and 2 combined with 375 mg/m2 rituximab on day 0 of the first course and 500 mg/m2 on day 1 during subsequent courses for up to six courses. Results Overall response rate was 88.0% (95% CI, 80.7% to 100.0%) with a complete response rate of 23.1% and a partial response rate of 64.9%. Ninety percent of patients with del(11q), 94.7% with trisomy 12, 37.5% with del(17p), and 89.4% with unmutated IGHV status responded to treatment. After a median observation time of 27.0 months, median event-free survival was 33.9 months, and 90.5% of patients were alive. Grade 3 or 4 severe infections occurred in 7.7% of patients. Grade 3 or 4 adverse events for neutropenia, thrombocytopenia, and anemia were documented in 19.7%, 22.2%, and 19.7% of patients, respectively. Conclusion Chemoimmunotherapy with BR is effective and safe in patients with previously untreated CLL.
Do Socially Deprived Urban Areas Have Lesser Supplies of Cancer Care Services?
Authors: Lamont Elizabeth B. , He Yulei , Subramanian S.V. , Zaslavsky Alan M. 
Published: August 2012

Purpose Area social deprivation is associated with unfavorable health outcomes of residents across the full clinical course of cancer from the stage at diagnosis through survival. We sought to determine whether area social factors are associated with the area health care supply. Patients and Methods We studied the area supply of health services required for the provision of guideline-recommended care for patients with breast cancer and colorectal cancer (CRC) in each of the following three distinct clinical domains: screening, treatment, and post-treatment surveillance. We characterized area social factors in 3,096 urban zip code tabulation areas by using Census Bureau data and the health care supply in the corresponding 465 hospital service areas by using American Hospital Association, American Medical Association, and US Food and Drug Administration data. In two-level hierarchical models, we assessed associations between social factors and the supply of health services across areas. Results We found no clear associations between area social factors and the supply of health services essential to the provision of guideline recommended breast cancer and CRC care in urban areas. The measures of health service included the supply of physicians who facilitate screening, treatment, and post-treatment care and the supply of facilities required for the same services. Conclusion Because we found that the supply of types of health care required for the provision of guideline-recommended cancer care for patients with breast cancer and CRC did not vary with markers of area socioeconomic disadvantage, it is possible that previously reported unfavorable breast cancer and CRC outcomes among individuals living in impoverished areas may have occurred despite an apparent adequate area health care supply.
Validation of a Prognostic Model and the Impact of Mutations in Patients With Lower-Risk Myelodysplastic Syndromes
Authors: Bejar Rafael , Stevenson Kristen E. , Caughey Bennett A. , Abdel-Wahab Omar , Steensma David P. , Galili Naomi , Raza Azra , Kantarjian Hagop , Levine Ross L. , Neuberg Donna , Garcia-Manero Guillermo , Ebert Benjamin L. 
Published: August 2012

Purpose A subset of patients with myelodysplastic syndromes (MDS) who are predicted to have lower-risk disease as defined by the International Prognostic Scoring System (IPSS) demonstrate more aggressive disease and shorter overall survival than expected. The identification of patients with greater-than-predicted prognostic risk could influence the selection of therapy and improve the care of patients with lower-risk MDS. Patients and Methods We performed an independent validation of the MD Anderson Lower-Risk Prognostic Scoring System (LR-PSS) in a cohort of 288 patients with low- or intermediate-1 IPSS risk MDS and examined bone marrow samples from these patients for mutations in 22 genes, including SF3B1, SRSF2, U2AF1, and DNMT3A. Results The LR-PSS successfully stratified patients with lower-risk MDS into three risk categories with significant differences in overall survival (20% in category 1 with median of 5.19 years [95% CI, 3.01 to 10.34 years], 56% in category 2 with median of 2.65 years [95% CI, 2.18 to 3.30 years], and 25% in category 3 with median of 1.11 years [95% CI, 0.82 to 1.51 years]), thus validating this prognostic model. Mutations were identified in 71% of all samples, and mutations associated with a poor prognosis were enriched in the highest-risk LR-PSS category. Mutations of EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival independent of the LR-PSS. Only EZH2 mutations retained prognostic significance in a multivariable model that included LR-PSS and other mutations (hazard ratio, 2.90; 95% CI, 1.85 to 4.52). Conclusion Combining the LR-PSS and EZH2 mutation status identifies 29% of patients with lower-risk MDS with a worse-than-expected prognosis. These patients may benefit from earlier initiation of disease-modifying therapy.
Murine Anti-GD2 Monoclonal Antibody 3F8 Combined With Granulocyte-Macrophage Colony-Stimulating Factor and 13-Cis-Retinoic Acid in High-Risk Patients With Stage 4 Neuroblastoma in First Remission
Authors: Cheung Nai-Kong V. , Cheung Irene Y. , Kushner Brian H. , Ostrovnaya Irina , Chamberlain Elizabeth , Kramer Kim , Modak Shakeel 
Published: August 2012

Purpose Anti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB). Prognostic variables that could influence clinical outcome were explored. Patients and Methods One hundred sixty-nine children diagnosed with stage 4 NB (1988 to 2008) were enrolled onto consecutive anti-GD2 murine MoAb 3F8 ± GM-CSF ± 13-cis-retinoic acid (CRA) protocols after achieving first remission (complete remission/very good partial remission). Patients enrolled in regimen A (n = 43 high-risk [HR] patients) received 3F8 alone; regimen B (n = 41 HR patients), 3F8 + intravenous GM-CSF + CRA, after stem-cell transplantation (SCT); and regimen C (n = 85), 3F8 + subcutaneous GM-CSF + CRA, 46 of 85 after SCT, whereas 28 of 85 required additional induction therapy and were deemed ultra high risk (UHR). Marrow minimal residual disease (MRD) was measured by quantitative reverse transcription polymerase chain reaction. Survival probability was calculated by the Kaplan-Meier method, and prognostic variables were analyzed by multivariate Cox regression model. Results At 5 years from the start of immunotherapy, progression-free survival (PFS) improved from 44% for HR patients receiving regimen A to 56% and 62% for those receiving regimens B and C, respectively. Overall survival (OS) was 49%, 61%, and 81%, respectively. PFS and OS of UHR patients were 36% and 75%, respectively. Relapse was mostly at isolated sites. Independent adverse prognostic factors included UHR (PFS) and post–cycle two MRD (PFS and OS), whereas the prognostic factors for improved outcome were missing killer immunoglobulin-like receptor ligand (PFS and OS), human antimouse antibody response (OS), and regimen C (OS). Conclusion Retrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only be confirmed definitively by randomized studies.
Bortezomib-Based Graft-Versus-Host Disease Prophylaxis in HLA-Mismatched Unrelated Donor Transplantation
Authors: Koreth John , Stevenson Kristen E. , Kim Haesook T. , McDonough Sean M. , Bindra Bhavjot , Armand Philippe , Ho Vincent T. , Cutler Corey , Blazar Bruce R. , Antin Joseph H. , Soiffer Robert J. , Ritz Jerome , Alyea Edwin P. 
Published: August 2012

Purpose HLA-mismatched unrelated donor (MMUD) hematopoietic stem-cell transplantation (HSCT) is associated with increased graft-versus-host disease (GVHD) and impaired survival. In reduced-intensity conditioning (RIC), neither ex vivo nor in vivo T-cell depletion (eg, antithymocyte globulin) convincingly improved outcomes. The proteasome inhibitor bortezomib has immunomodulatory properties potentially beneficial for control of GVHD in T-cell-replete HLA-mismatched transplantation. Patients and Methods We conducted a prospective phase I/II trial of a GVHD prophylaxis regimen of short-course bortezomib, administered once per day on days +1, +4, and +7 after peripheral blood stem-cell infusion plus standard tacrolimus and methotrexate in patients with hematologic malignancies undergoing MMUD RIC HSCT. We report outcomes for 45 study patients: 40 (89%) 1-locus and five (11%) 2-loci mismatches (HLA-A, -B, -C, -DRB1, or -DQB1), with a median of 36.5 months (range, 17.4 to 59.6 months) follow-up. Results The 180-day cumulative incidence of grade 2 to 4 acute GVHD was 22% (95% CI, 11% to 35%). One-year cumulative incidence of chronic GVHD was 29% (95% CI, 16% to 43%). Two-year cumulative incidences of nonrelapse mortality (NRM) and relapse were 11% (95% CI, 4% to 22%) and 38% (95% CI, 24% to 52%), respectively. Two-year progression-free survival and overall survival were 51% (95% CI, 36% to 64%) and 64% (95% CI, 49% to 76%), respectively. Bortezomib-treated HLA-mismatched patients experienced rates of NRM, acute and chronic GVHD, and survival similar to those of contemporaneous HLA-matched RIC HSCT at our institution. Immune recovery, including CD8+ T-cell and natural killer cell reconstitution, was enhanced with bortezomib. Conclusion A novel short-course, bortezomib-based GVHD regimen can abrogate the survival impairment of MMUD RIC HSCT, can enhance early immune reconstitution, and appears to be suitable for prospective randomized evaluation.
Primary mFOLFOX6 Plus Bevacizumab Without Resection of the Primary Tumor for Patients Presenting With Surgically Unresectable Metastatic Colon Cancer and an Intact Asymptomatic Colon Cancer: Definitive Analysis of NSABP Trial C-10
Authors: McCahill Laurence E. , Yothers Greg , Sharif Saima , Petrelli Nicholas J. , Lai Lily Lau , Bechar Naftali , Giguere Jeffrey K. , Dakhil Shaker R. , Fehrenbacher Louis , Lopa Samia H. , Wagman Lawrence D. , O'Connell Michael J. , Wolmark Norman 
Published: August 2012

Purpose Major concerns surround combining chemotherapy with bevacizumab in patients with colon cancer presenting with an asymptomatic intact primary tumor (IPT) and synchronous yet unresectable metastatic disease. Surgical resection of asymptomatic IPT is controversial. Patients and Methods Eligibility for this prospective, multicenter phase II trial included Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1, asymptomatic IPT, and unresectable metastases. All received infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) combined with bevacizumab. The primary end point was major morbidity events, defined as surgical resection because of symptoms at or death related to the IPT. A 25% major morbidity rate was considered acceptable. Secondary end points included overall survival (OS) and minor morbidity related to IPT requiring hospitalization, transfusion, or nonsurgical intervention. Results Ninety patients registered between March 2006 and June 2009: 86 were eligible with follow-up, median age was 58 years, and 52% were female. Median follow-up was 20.7 months. There were 12 patients (14%) with major morbidity related to IPT: 10 required surgery (eight, obstruction; one, perforation; and one, abdominal pain), and two patients died. The 24-month cumulative incidence of major morbidity was 16.3% (95% CI, 7.6% to 25.1%). Eleven IPTs were resected without a morbidity event: eight for attempted cure and three for other reasons. Two patients had minor morbidity events only: one hospitalization and one nonsurgical intervention. Median OS was 19.9 months (95% CI, 15.0 to 27.2 months). Conclusion This trial met its primary end point. Combining mFOLFOX6 with bevacizumab did not result in an unacceptable rate of obstruction, perforation, bleeding, or death related to IPT. Survival was not compromised. These patients can be spared initial noncurative resection of their asymptomatic IPT.
Synthesis of Pyrene-Based Ester Dendrimers for Applications in Dye-Sensitized Solar Cells
Authors: Rajakumar Perumal , Visalakshi Kathiresan , Ganesan Shanmugam , Maruthamuthu Pichai , Suthanthiraraj Samuel Austin 
Published: August 2012

Abstract
Synthesis of dendrimers with pyrene at the surface and benzenetricarboxylic acid and phloroglucinol at the core and with ester functionality as branching points has been described. When such dendrimers are used as an additive in DSSC, power conversion efficiency of 6.78% is observed.
Malarial acute kidney injury in a paediatric intensive care unit
Authors: Kapoor Kapil , Gupta Shalu 
Published: August 2012

Summary Acute kidney injury (AKI) is a serious complication of malaria which has a very high mortality rate. A retrospective analysis of medical record data of children treated for malarial AKI in a paediatric intensive care unit (PICU) was performed in order to evaluate the incidence, poor prognostic factors and outcome of AKI with malaria. Eighteen (48.6%) malarial patients had AKI (11 Plasmodium vivax positive, six P. falciparum positive and one mixed infection) with a male-to-female ratio of 1:2. The mean age was 75 ± 32 months (range, 1 month to 10 years). Oliguria was present in 61.1% and 55.5% required renal replacement therapy. Mortality was noted in 33.3% of patients and full recovery was achieved in 50% of patients. Oliguria, shock, central nervous system involvement, jaundice, disseminated intravascular coagulopathy and acute respiratory distress syndrome emerged as bad prognostic factors in simple univariate analysis. Malaria patients with and without AKI differ significantly in terms of shock, ventilator requirement, mortality and length of PICU stay.
Privacy and Security Assessment of Biometric Template Protection
Authors: Zhou Xuebing 
Published: August 2012

Abstract
Template-Protection-Techniken stellen eine wichtige Ergänzung zu biometrischen Systemen, um das gewünschte Sicherheitsniveau zu erreichen und die Anforderungen an den Schutz der Privatsphäre zu erfüllen. Diese Techniken ermöglichen Erneuerung und Widerruf der Referenzendaten in biometrischen Systemen. In dieser Arbeit wird ein systematisches Evaluierungsframework entwickelt, das sich an die wesentlichen Kriterien und Anforderungen an biometrische Template-Protection-Verfahren festhält. Seine Anwendbarkeit wird durch die Analyse der verschiedenen Algorithmen demonstriert. Die in dieser Arbeit präsentierte Evaluierung ist grundlegend für eine vollständige Analyse. Darüber hinaus ermöglicht es einen Nachweis der Sicherheit und Einhaltung der Privatsphäre. Es schafft eine Basis für Zertifizierung und Benchmark der Template-Protection-Verfahren.