bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity
Authors: Zizzo Gaetano , Guerrieri Justus , Dittman Lindsay M , Merrill Joan T , Cohen Philip L 
Published: December 2013

Abstract
Introduction
Systemic lupus erythematosus (SLE) is characterized by impaired efferocytosis and aberrant activation of innate immunity. We asked if shedding of MER receptor tyrosine kinase (MerTK) and AXL into soluble (s) ectodomains was related to immunological and clinical aspects of SLE.

Methods
Levels of sMER and sAXL in the plasma of 107 SLE patients and 45 matched controls were measured by ELISA. In 40 consecutive SLE patients, we examined potential correlations between either sMER or sAXL and plasma levels of sCD163, a marker of M2 activation. All three soluble receptors were measured in supernatants of monocytes/macrophages cultured in various immunological conditions. Membrane expression of MerTK, AXL and CD163 was assessed by flow cytometry.

Results
Both sMER and sAXL were associated with anti-chromatin and anti-phospholipid autoantibodies, and with hematological and renal involvement. However, sMER and sAXL did not significantly correlate with each other; sAXL correlated with growth arrest-specific 6 (Gas6), whereas sMER correlated with reduced free protein S (PROS) levels. Only sMER showed significant associations with lupus-specific anti-dsDNA, anti-Sm, anti-ribonucleoprotein (anti-RNP) and anti-Ro60 autoantibodies. Strong correlations with disease activity indices (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), complement reduction, titer of circulating anti-dsDNA) were found for sMER, not for sAXL. Patients with active SLEDAI, nephritis, anti-dsDNA and anti-Ro60 positivity showed higher levels of sMER compared to controls. Levels of sMER, not sAXL, correlated with sCD163 levels, and these correlated with SLEDAI. Production of sMER and sCD163 occurred under “M2c” polarizing conditions, whereas sAXL was released upon type-I IFN exposure.

Conclusions
Alterations in homeostasis of anti-inflammatory and efferocytic “M2c” monocytes/macrophages may have a role in immunopathogenesis of SLE.
Evaluation of ultra-deep targeted sequencing for personalized breast cancer care
Authors: Harismendy Olivier , Schwab Richard B , Alakus Hakan , Yost Shawn E , Matsui Hiroko , Hasteh Farnaz , Wallace Anne M , Park Hannah L , Madlensky Lisa , Parker Barbara , Carpenter Philip M , Jepsen Kristen , Anton-Culver Hoda , Frazer Kelly A 
Published: December 2013

Abstract
Introduction
The increasing number of targeted therapies, together with a deeper understanding of cancer genetics and drug response, have prompted major healthcare centers to implement personalized treatment approaches relying on high-throughput tumor DNA sequencing. However, the optimal way to implement this transformative methodology is not yet clear. Current assays may miss important clinical information such as the mutation allelic fraction, the presence of sub-clones or chromosomal rearrangements, or the distinction between inherited variants and somatic mutations. Here, we present the evaluation of ultra-deep targeted sequencing (UDT-Seq) to generate and interpret the molecular profile of 38 breast cancer patients from two academic medical centers.

Methods
We sequenced 47 genes in matched germline and tumor DNA samples from 38 breast cancer patients. The selected genes, or the pathways they belong to, can be targeted by drugs or are important in familial cancer risk or drug metabolism.

Results
Relying on the added value of sequencing matched tumor and germline DNA and using a dedicated analysis, UDT-Seq has a high sensitivity to identify mutations in tumors with low malignant cell content. Applying UDT-Seq to matched tumor and germline specimens from the 38 patients resulted in a proposal for at least one targeted therapy for 22 patients, the identification of tumor sub-clones in 3 patients, the suggestion of potential adverse drug effects in 3 patients and a recommendation for genetic counseling for 2 patients.

Conclusion
Overall our study highlights the additional benefits of a sequencing strategy, which includes germline DNA and is optimized for heterogeneous tumor tissues.
Decreased HLA-DR antigen-associated invariant chain (CD74) mRNA expression predicts mortality after septic shock
Authors: Cazalis Marie-Angélique , Friggeri Arnaud , Cavé Laura , Demaret Julie , Barbalat Véronique , Cerrato Elisabeth , Lepape Alain , Pachot Alexandre , Monneret Guillaume , Venet Fabienne 
Published: December 2013

Abstract
Introduction
Septic syndromes remain the leading cause of mortality in intensive care units (ICU). Septic patients rapidly develop immune dysfunctions, the intensity and duration of which have been linked with deleterious outcomes. Decreased mRNA expressions of major histocompatibility complex (MHC) class II-related genes have been reported after sepsis. We investigated whether their mRNA levels in whole blood could predict mortality in septic shock patients.

Methods
A total of 93 septic shock patients were included. On the third day after shock, the mRNA expressions of five MHC class II-related genes (CD74, HLA-DRA, HLA-DMB, HLA-DMA, CIITA) were measured by qRT-PCR and monocyte human leukocyte antigen-DR (mHLA-DR) by flow cytometry.

Results
A significant correlation was found among MHC class II related gene expressions. Among mRNA markers, the best prognostic value was obtained for CD74 (HLA-DR antigen-associated invariant chain). For this parameter, the area under the receiver operating characteristic curve (AUC) was calculated (AUC = 0.67, 95% confidence interval (CI) = 0.55 to 0.79; P = 0.01) as well as the optimal cut-off value. After stratification based on this threshold, survival curves showed that a decreased CD74 mRNA level was associated with increased mortality after septic shock (Log rank test, P = 0.0043, Hazard Ratio = 3.0, 95% CI: 1.4 to 6.5). Importantly, this association remained significant after multivariate logistic regression analysis including usual clinical confounders (that is, severity scores, P = 0.026, Odds Ratio = 3.4, 95% CI: 1.2 to 9.8).

Conclusion
Decreased CD74 mRNA expression significantly predicts 28-day mortality after septic shock. After validation in a larger multicentric study, this biomarker could become a robust predictor of death in septic patients.
Loss of Major Molecular Response As a Trigger for Restarting Tyrosine Kinase Inhibitor Therapy in Patients With Chronic-Phase Chronic Myelogenous Leukemia Who Have Stopped Imatinib After Durable Undetectable Disease
Authors: Rousselot Philippe , Charbonnier Aude , Cony-Makhoul Pascale , Agape Philippe , Nicolini Franck E. , Varet Bruno , Gardembas Martine , Etienne Gabriel , Réa Delphine , Roy Lydia , Escoffre-Barbe Martine , Guerci-Bresler Agnès , Tulliez Michel , Prost Stéphane , Spentchian Marc , Cayuela Jean Michel , Reiffers Josy , Chomel Jean Claude , Turhan Ali , Guilhot Joëlle , Guilhot François , Mahon François-Xavier 
Published: December 2013

Purpose More than half of patients with chronic-phase chronic myelogenous leukemia (CP-CML) in complete molecular response (CMR) experience molecular relapse after imatinib discontinuation. We investigated loss of major molecular response (MMR) as a criterion for resuming therapy. Patients and Methods A multicenter observational study (A-STIM [According to Stop Imatinib]) evaluating MMR persistence was conducted in 80 patients with CP-CML who had stopped imatinib after prolonged CMR. Results Median time from imatinib initiation to discontinuation was 79 months (range, 30 to 145 months);median duration of CMR before imatinib discontinuation was 41 months (range, 24 to 96 months); median follow-up after discontinuation was 31 months (range, 8 to 92 months). Twenty-nine patients (36%) lost MMR after a median of 4 months off therapy (range, 2 to 17 months). Cumulative incidence of MMR loss was estimated as 35% (95% CI, 25% to 46%) at 12 months and 36% (95% CI, 26% to 47%) at 24 months, whereas probability of losing CMR was higher. Fluctuation of BCR-ABL transcript levels below the MMR threshold (≥ two consecutive positive values) was observed in 31% of patients after imatinib discontinuation. Treatment-free remission was estimated as 64% (95% CI, 54% to 75%) at 12 and 24 months and 61% (95% CI, 51% to 73%) at 36 months. Median to time to second CMR was estimated as 7.3 months in re-treated patients. Conclusion Loss of MMR is a practical and safe criterion for restarting therapy in patients with CML with prolonged CMR.
Targeted Androgen Pathway Suppression in Localized Prostate Cancer: A Pilot Study
Authors: Mostaghel Elahe A. , Nelson Peter S. , Lange Paul , Lin Daniel W. , Taplin Mary Ellen , Balk Steven , Ellis William , Kantoff Philip , Marck Brett , Tamae Daniel , Matsumoto Alvin M. , True Lawrence D. , Vessella Robert , Penning Trevor , Hunter Merrill Rachel , Gulati Roman , Montgomery Bruce 
Published: December 2013

Purpose Ligand-mediated activation of the androgen receptor (AR) is critical for prostate cancer (PCa) survival and proliferation. The failure to completely ablate tissue androgens may limit suppression of PCa growth. We evaluated combinations of CYP17A and 5-α-reductase inhibitors for reducing prostate androgen levels, AR signaling, and PCa volumes. Patients and Methods Thirty-five men with intermediate/high-risk clinically localized PCa were randomly assigned to goserelin combined with dutasteride (ZD), bicalutamide and dutasteride (ZBD), or bicalutamide, dutasteride, and ketoconazole (ZBDK) for 3 months before prostatectomy. Controls included patients receiving combined androgen blockade with luteinizing hormone-releasing hormone agonist and bicalutamide. The primary outcome measure was tissue dihydrotestosterone (DHT) concentration. Results Prostate DHT levels were substantially lower in all experimental arms (0.02 to 0.04 ng/g v 0.92 ng/g in controls; P < .001). The ZBDK group demonstrated the greatest percentage decline in serum testosterone, androsterone, and dehydroepiandrosterone sulfate (P < .05 for all). Staining for AR and the androgen-regulated genes prostate-specific antigen and TMPRSS2 was strongly suppressed in benign glands and moderately in malignant glands (P < .05 for all). Two patients had pathologic complete response, and nine had ≤ 0.2 cm3 of residual tumor (defined as a near-complete response), with the largest numbers of complete and near-complete responses in the ZBDK group. Conclusion Addition of androgen synthesis inhibitors lowers prostate androgens below that achieved with standard therapy, but significant AR signaling remains. Tissue-based analysis of steroids and AR signaling is critical to informing the search for optimal local and systemic control of high-risk prostate cancer.
Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients
Authors: Kim Youngwook , Hammerman Peter S. , Kim Jaegil , Yoon Ji-ae , Lee Yoomi , Sun Jong-Mu , Wilkerson Matthew D. , Pedamallu Chandra Sekhar , Cibulskis Kristian , Yoo Yeong Kyung , Lawrence Michael S. , Stojanov Petar , Carter Scott L. , McKenna Aaron , Stewart Chip , Sivachenko Andrey Y. , Oh In-Jae , Kim Hong Kwan , Choi Yong Soo , Kim Kwhanmien , Shim Young Mog , Kim Kyu-Sik , Song Sang-Yun , Na Kook-Joo , Choi Yoon-La , Hayes D. Neil , Kim Jhingook , Cho Sukki , Kim Young-Chul , Ahn Jin Seok , Ahn Myung-Ju , Getz Gad , Meyerson Matthew , Park Keunchil 
Published: December 2013

PurposeLung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients.Patients and MethodsWe performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.ResultsThis cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC.ConclusionThese findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.
Clock Time, National Space, and the Limits of Guomindang Anti-Imperialism
Authors: Tsui Brian 
Published: December 2013

This article examines the politics of time and space in Nationalist China in connection with the regime's compromised anti-imperialism. It demonstrates that the Guomindang's nation-building project, which failed to confront capitalist social relations and the imperialist powers that underpinned them, overdetermined the party-state's ambivalent attitude toward modernity. The school campuses on which the Guomindang projected its social vision were, on the one hand, constructed as efficient, mechanical-clock-timed training grounds of wage laborers and, on the other hand, spaces of authenticity and beauty free from social alienation. This search for aestheticized spaces outside capitalism, in combination with a rejection of fundamental social changes, put the Guomindang in ideological league with radical right-wing movements active around the world between the two world wars.
My exposition of the Guomindang's ideological import serves as a critique of recent scholarship that tends to subsume the Guomindang and its peculiar approach to capitalism under a blanket denunciation of modern political movements. Adopting a poststructuralist suspicion of post-Enlightenment rationality, some scholars of China view twentieth-century history as a unilinear succession of nation-states that, regardless of ideological affiliation, destroyed pluralistic local particularities and everyday idiosyncrasies in favor of national unity and industrial productivity. The communist movement is, according to this view, equally guilty as the Guomindang in perpetuating this process. I argue that this one-dimensional reading of political modernity not only trivializes the politics of competing revolutions but abstracts everyday experiences as basic as those of space and time from their embeddedness in larger social relations.
Adverse Drug Reactions: A Retrospective Review of Hospitalized Patients at a State Psychiatric Hospital
Authors: Iuppa Courtney A. , Nelson Leigh Anne , Elliott Ellie , Sommi Roger W. 
Published: December 2013

Background There is a paucity of information regarding adverse drug reactions (ADRs) in psychiatric patients. Information on common and preventable ADRs (pADRs) in psychiatric patients will allow for targeted improvement projects. Objective To characterize reported ADRs and pharmacist interventions to prevent ADRs in an extended-care state psychiatric hospital. Methods Four years of ADR reports were assessed for probability, reaction severity, pharmacological class of medication involved, preventability, change in therapy, and transfers to a medical facility. The pharmacist intervention database was queried for interventions classified as “prevention of ADR.” The interventions were assessed for type of medication and recommendation acceptance. Results Medication classes responsible for ADRs included mood stabilizers (30%), typical antipsychotics (25%), atypical antipsychotics (25%), and antidepressants (8%). Nine percent resulted in transfer to a medical facility. Of all ADRs, 34.4% were pADRs; mood stabilizers (41%) and atypical antipsychotics (27%) were the most common pADRs. The most common causes of pADRs were supratherapeutic serum concentrations, drug-drug interactions, and history of reaction. There were 87 pharmacist interventions that were classified as “prevention of ADR,” and the acceptance rate of pharmacists’ recommendations was 96.5%. Mood stabilizers (20%), atypical antipsychotics (17%), and typical antipsychotics (11%) were commonly associated with prevented ADRs. Lithium accounted for 13.8% of prevented ADRs; these ADRs were most often due to a drug–drug interaction with a nonsteroidal anti-inflammatory drug. Conclusions ADRs were most commonly associated with mood stabilizers and antipsychotics, and pADRs were common. There is an opportunity to provide education to medical staff on therapeutic drug monitoring and drug–drug interactions for these classes, particularly lithium.
Fetal ovarian cyst: 2- and 3-dimensional ultrasound as a new diagnostic method to rule out ovarian torsion
Authors: Triunfo Stefania , Rosati Paolo , Lanzone Antonio , Scambia Giovanni 
Published: December 2013

Abstract
Owing to the improvement in obstetric ultrasound imaging, prenatal diagnosis of ovarian masses has increased considerably. Fetal ovarian cysts can be suspected when an ultrasound scan shows intra-abdominal structures in female fetuses in the presence of normal bowel and urinary structures. The most common complication is the adnexal torsion, causing partial or complete strangulation of blood supply via ovarian vessels, leading ovarian ischemia, or necrosis. Current information regarding the treatment of fetal ovarian cysts is based on personal experiences and some case series. The management is controversial, characterized by dissimilar approaches, such as “wait and see”, prenatal or postnatal aspiration, or neonatal surgery. In more than half of the cases, spontaneous regression occurs in the prenatal or postnatal period, probably due to the small size and simple aspect. Large cysts may cause both local effects (adnexal torsion, ovarian autoamputation), and distant effects (intestinal and urinary obstruction, adhesion with adjacent organs, abdominal and thoracic mass effect, pulmonary hypoplasia, hemoperitoneum, ascites, polyhyramniosis). In the absence of accurate guidelines for management, we must start with the development of more accurate methods for diagnosing associated complications such as torsion. This case report describes the role of three-dimensional (3-D) ultrasonography as potential diagnostic method for ruling out adnexal torsion when an ovarian cyst is present.
Pulp delignification with oxygen and copper(II)-polyimine complexes
Authors: Gueneau Basile , Marlin Nathalie , Deronzier Alain , Lachenal Dominique 
Published: December 2013

Abstract
Ten Cu(II)-polyimine complexes were tested as potential catalysts in oxygen delignification of softwood kraft pulps. The ligands were chosen from the terpyridine and the phenanthroline families, including several neocuproines. One diamine-phenanthrene (daphen) was also investigated. The main purpose was to examine whether the presence of methyl or phenyl substituents would direct the oxidation toward lignin. As a catalyst for comparison, unsubstituted 1,10-phenanthroline was selected, which is known to activate both delignification and carbohydrate degradation during oxygen bleaching of kraft pulp. The variation of ligands was aiming at the complex solubility and redox potential of the parameters. The experiments were performed on a mixture of mechanical pulp and fully bleached kraft pulps, a fully bleached pulp alone, and an industrial unbleached pulp. Concerning the oxygen activation in delignification of kraft pulp, 4,7-diphenyl-1,10-phenanthroline was as good as 1,10-phenanthroline, but appeared to be more selective, which resulted in a higher DPv of cellulose after treatment. This was interpreted by the structural similarities between the ligand and the kraft lignin and by a better stability of the intermediate complex with lignin. Two Cu(II)-phenanthroline derivatives complexes (4,7- and 5,6-dimethyl-1,10-phenanthroline) were also identified as effective oxygen activators for the removal of native lignin.
Off-axis tensile strength and evaluation of the in-plane shear strength of paper
Authors: Yoshihara Hiroshi , Yoshinobu Masahiro 
Published: December 2013

Abstract
The off-axis tensile strength (OATS) of copy paper, filter paper, and sack paper was obtained from dog-bone specimens. The relationship between OATS and the off-axis angle (OAA) was predicted under several failure conditions. Additionally, the shear strengths (SS) of these papers were evaluated based on the results of OAT tests. The OATS could be accurately predicted under several Hill-type failure conditions. An equation for deriving the in-plane SS of these papers was proposed based on the tensile strength of the specimen with a 35° OAA, in which the contribution of the shear stress component was maximum.
The Wsc1p Cell Wall Signaling Protein Controls Biofilm (Mat) Formation Independently of Flo11p in Saccharomyces cerevisiae
Authors: Sarode Neha , Davis Sarah E , Tams Robert N , Reynolds Todd B 
Published: December 2013

Abstract
Saccharomyces cerevisiae strains of the ∑1278b background generate biofilms, referred to as mats, on low-density agar (0.3%) plates made with rich media (YPD). Mat formation involves adhesion of yeast cells to the surface of the agar substrate and each other as the biofilm matures, resulting in elaborate water channels that create filigreed patterns of cells. The cell wall adhesion protein Flo11p is required for mat formation; however, genetic data indicate that other unknown effectors are also required. For example, mutations in vacuolar protein sorting genes that affect the multivesicular body pathway, such as vps27∆, cause mat formation defects independently of Flo11p, presumably by affecting an unidentified signaling pathway. A cell wall signaling protein, Wsc1p, found at the plasma membrane is affected for localization and function by vps27∆. We found that a wsc1∆ mutation disrupted mat formation in a Flo11p-independent manner. Wsc1p appears to impact mat formation through the Rom2p-Rho1p signaling module, by which Wsc1p also regulates the cell wall. The Bck1p, Mkk1/Mkk2, Mpk1p MAP kinase signaling cascade is known to regulate the cell wall downstream of Wsc1p-Rom2p-Rho1p but, surprisingly, these kinases do not affect mat formation. In contrast, Wsc1p may impact mat formation by affecting Skn7p instead. Skn7p can also receive signaling inputs from the Sln1p histidine kinase; however, mutational analysis of specific histidine kinase receiver residues in Skn7p indicate that Sln1p does not play an important role in mat formation, suggesting that Skn7p primarily acts downstream of Wsc1p to regulate mat formation.