bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo targeting and growth inhibition of the A20 murine B-cell lymphoma by an idiotype-specific peptide binder
Authors: Palmieri Camillo , Falcone Cristina , Iaccino Enrico , Tuccillo Franca Maria , Gaspari Marco , Trimboli Francesca , De Laurentiis Annamaria , Luberto Laura , Pontoriero Marilena , Pisano Antonio , Vecchio Eleonora , Fierro Olga , Panico Maria Rosaria , Larobina Michele , Gargiulo Sara , Costa Nicola , Dal Piaz Fabrizio , Schiavone Marco , Arra Claudio , Giudice Aldo , Palma Giuseppe , Barbieri Antonio , Quinto Ileana , Scala Giuseppe 
Published: April 2010

AbstractB-cell lymphoma is a clonal expansion of neoplastic cells that may result in fatal outcomes. Here, we report the in vivo targeting and growth inhibition of aggressive A20 murine B-cell lymphoma by idiotype-specific peptide pA20-36. pA20-36 was selected from random peptide libraries and bound specifically to the B-cell receptor (BCR) of A20 cells in mice engrafted with A20 lymphoma, as shown by histology and positron emission tomographic analysis. BCR cross-linking of A20 cells with pA20-36 resulted in massive apoptosis of targeted tumor cells and in an increased survival of the diseased animals without any detectable evidence of toxicity. The pA20-36 treatment reverted the immune suppression of the tumor microenvironment as shown by reduced expression of vascular endothelial growth factor, interleukin-10, and transforming growth factor-β cytokines together with a lower number of CD11b+Gr-1+ inhibitor myeloid-derived suppressor cells and Foxp3+CD4+ Treg cells. Furthermore, pA20-36 treatment was associated with an increased number of tumor-infiltrating, activated CD8+ T cells that exerted a tumor-specific cytolytic activity. These findings show that a short peptide that binds specifically to the complementarity-determining regions of the A20 BCR allows in vivo detection of neoplastic cells together with significant inhibition of tumor growth in vivo.
WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system
Authors: Hou Hsin-An , Huang Tai-Chung , Lin Liang-In , Liu Chieh-Yu , Chen Chien-Yuan , Chou Wen-Chien , Tang Jih-Luh , Tseng Mei-Hsuan , Huang Chi-Fei , Chiang Ying-Chieh , Lee Fen-Yu , Liu Ming-Chih , Yao Ming , Huang Shang-Yi , Ko Bor-Sheng , Hsu Szu-Chun , Wu Shang-Ju , Tsay Woei , Chen Yao-Chang , Tien Hwei-Fang 
Published: April 2010

Abstract
The impact of WT1 mutations in acute myeloid leukemia (AML) is not completely settled. We aimed to determine the clinical implication of WT1 mutation in 470 de novo non-M3 AML patients and its stability during the clinical course. WT1 mutations were identified in 6.8% of total patients and 8.3% of younger patients with normal karyotype (CN-AML). The WT1 mutation was closely associated with younger age (P < .001), French-American-British M6 subtype (P = .006), and t(7;11)(p15;p15) (P = .003). Multivariate analysis demonstrated that the WT1 mutation was an independent poor prognostic factor for overall survival and relapse-free survival among total patients and the CN-AML group. A scoring system incorporating WT1 mutation, NPM1/FLT3-ITD, CEBPA mutations, and age into survival analysis proved to be very useful to stratify CN-AML patients into different prognostic groups (P < .001). Sequential analyses were performed on 133 patients. WT1 mutations disappeared at complete remission in all WT1-mutated patients studied. At relapse, 3 of the 16 WT1-mutated patients who had paired samples lost the mutation and 2 acquired additional mutations, whereas 3 of 110 WT1-wild patients acquired novel mutations. In conclusion, WT1 mutations are correlated with poor prognosis in AML patients. The mutation status may be changed in some patients during AML progression.
Drug target prediction and prioritization: using orthology to predict essentiality in parasite genomes
Authors: Doyle Maria A , Gasser Robin B , Woodcroft Ben J , Hall Ross S , Ralph Stuart A 
Published: April 2010

AbstractBackgroundNew drug targets are urgently needed for parasites of socio-economic importance. Genes that are essential for parasite survival are highly desirable targets, but information on these genes is lacking, as gene knockouts or knockdowns are difficult to perform in many species of parasites. We examined the applicability of large-scale essentiality information from four model eukaryotes,Caenorhabditis elegans, Drosophila melanogaster, Mus musculusandSaccharomyces cerevisiae, to discover essential genes in each of their genomes. Parasite genes that lack orthologues in their host are desirable as selective targets, so we also examined prediction of essential genes within this subset.ResultsCross-species analyses showed that the evolutionary conservation of genes and the presence of essential orthologues are each strong predictors of essentiality in eukaryotes. Absence of paralogues was also found to be a general predictor of increased relative essentiality. By combining several orthology and essentiality criteria one can select gene sets with up to a five-fold enrichment in essential genes compared with a random selection. We show how quantitative application of such criteria can be used to predict a ranked list of potential drug targets fromAncylostoma caninumandHaemonchus contortus- two blood-feeding strongylid nematodes, for which there are presently limited sequence data but no functional genomic tools.ConclusionsThe present study demonstrates the utility of using orthology information from multiple, diverse eukaryotes to predict essential genes. The data also emphasize the challenge of identifying essential genes among those in a parasite that are absent from its host.
Students' perceptions about the transition to the clinical phase of a medical curriculum with preclinical patient contacts; a focus group study
Authors: Godefrooij Merijn B , Diemers Agnes D , Scherpbier Albert JJA 
Published: April 2010

Abstract

Background
Studies have shown that medical students experience the transition between preclinical and clinical training as a stressful period. They are generally frustrated by their inability to apply their knowledge to solve clinical problems in practice. Preclinical patient contacts may offer a solution to this 'shock of practice.' We studied how students who have had preclinical patient contacts perceive the transition from preclinical to clinical training and, more specifically, how they value these early patient contacts as preparation for learning in clinical practice.

Methods
A purposive sample of 21 students participated in three focus groups which met twice during their first weeks of clinical clerkships. The interviews were recorded and transcribed literally. Qualitative content analysis of the transcriptions was performed.

Results
According to the students, working in clinical practice was enjoyable, motivated them to study and helped them to develop non-analytical reasoning skills. The students experienced stress due to increased working hours and work load, uncertainty as to what was expected of them and self-perceived lack of knowledge. They did not experience a major gap between the preclinical and clinical phase and felt well prepared for the clerkships. The preclinical patient contacts were considered to be instrumental in this.

Conclusions
Early patient contacts seem to ameliorate the shock of practice and prepare students for clinical work. The problems mentioned by the students in this study are mainly related to the socialisation process. The results of this study have to be validated by quantitative research.
Changes in the accessibility of the HIV-1 Integrase C-terminus in the presence of cellular proteins
Authors: Benkhelifa-Ziyyat Sofia , Bucher Stéphanie , Zanta-Boussif Maria-Antonietta , Pasquet Julie , Danos Olivier 
Published: April 2010

Abstract

Background
Following entry, uncoating, and reverse transcription, a number of cellular proteins become associated with the Human Immunodeficiency Virus type 1 (HIV-1) pre-integration complex (PIC). With the goal of obtaining reagents for the analysis of the HIV-1 PIC composition and localisation, we have constructed functional integrase (IN) and matrix (MA) proteins that can be biotinylated during virus production and captured using streptavidin-coated beads.

Results
Although the labelled C-terminus allows for the sensitive detection of virion-associated IN, it becomes inaccessible in the presence of cellular proteins. This masking is not dependent on the nature of the tag and does not occur with the tagged MA. It was not observed either with an IN mutant unable to interact with LEDGF/p75, or when LEDGF/p75 was depleted from cells.

Conclusion
Our observation suggests that a structural rearrangement or oligomerization of the IN protein occurs during the early steps of infection and that this process is related to the presence of LEDGF/p75.
An outbreak of aseptic meningitis caused by coxsackievirus A9 in Gansu, the People's Republic of China
Authors: Cui Aili , Yu Deshan , Zhu Zhen , Meng Lei , Li Hui , Liu Jianfeng , Liu Guiyan , Mao Naiying , Xu Wenbo 
Published: April 2010

Abstract

Background
An outbreak of aseptic meningitis occurred in Tianshui city of Gansu Province, the People's Republic of China, from March to June 2005. A total of 85 patients were clinical confirmed as aseptic meningitis in this outbreak.

Results
CVA9 was mainly responsible for this outbreak supported by the clinical manifestations of the patients, epidemiological data of the outbreak, the results of RT-PCR and complete VP1 sequence determination, conventional neutralization assays, IgM serological assays, viral isolation and phylogenetics analysis. Through phylogenetic analysis and homogeneity analysis for partial VP1 gene, the nucleotide and amino acid homologies between Gansu isolates and former Chinese CVA9 strains were 88.2%-96.1% and 97.2%-99.2%, respectively. Multiple transmission chains of CVA9 occurred in different provinces or years in China. Moreover, in order to clarify the genotype of CVA9, Gansu CVA9 strains isolated in this outbreak were compared with other CVA9 isolates based on VP1/2A junction regions (genotyping region) and they might belong to a new genotype of CVA9, which could be assigned for genotype XIII,

Conclusions
CVA9 was confirmed as the pathogen responsible for this outbreak. The phylogenetic analysis indicated that the CVA9 strains isolated in this outbreak might belong to a new genotype.
Surveillance of FAP: a prospective blinded comparison of capsule endoscopy and other GI imaging to detect small bowel polyps
Authors: Tescher Paul , Macrae Finlay A , Speer Tony , Stella Damien , Gibson Robert , Tye-Din Jason A , Srivatsa Geeta , Jones Ian T , Marion Kaye 
Published: April 2010

Abstract

Background
Familial adenomatous polyposis (FAP) is a hereditary disorder characterized by polyposis along the gastrointestinal tract. Information on adenoma status below the duodenum has previously been restricted due to its inaccessibility in vivo. Capsule Endoscopy (CE) may provide a useful adjunct in screening for polyposis in the small bowel in FAP patients. This study aims to evaluate the effectiveness of CE in the assessment of patients with FAP, compared to other imaging modalities for the detection of small bowel polyps.

Method
20 consecutive patients with previously diagnosed FAP and duodenal polyps, presenting for routine surveillance of polyps at The Royal Melbourne Hospital were recruited. Each fasted patient initially underwent a magnetic resonance image (MRI) of the abdomen, and a barium small bowel follow-through study. Capsule Endoscopy was performed four weeks later on the fasted patient. An upper gastrointestinal side-viewing endoscopy was done one (1) to two (2) weeks after this. Endoscopists and investigators were blinded to results of other investigations and patient history.

Results
Within the stomach, upper gastrointestinal endoscopy found more polyps than other forms of imaging. SBFT and MRI generally performed poorly, identifying fewer polyps than both upper gastrointestinal and capsule endoscopy. CE was the only form of imaging that identified polyps in all segments of the small bowel as well as the only form of imaging able to provide multiple findings outside the stomach/duodenum.

Conclusion
CE provides important information on possible polyp development distal to the duodenum, which may lead to surgical intervention. The place of CE as an adjunct in surveillance of FAP for a specific subset needs consideration and confirmation in replication studies.

Trial Registration
Australian New Zealand Clinical Trials Registry ACTRN12608000616370
Development of a Multimarker Assay for Early Detection of Ovarian Cancer
Authors: Yurkovetsky Zoya , Skates Steven , Lomakin Aleksey , Nolen Brian , Pulsipher Trenton , Modugno Francesmary , Marks Jeffrey , Godwin Andrew , Gorelik Elieser , Jacobs Ian , Menon Usha , Lu Karen , Badgwell Donna , Bast Robert C. , Lokshin Anna E. 
Published: April 2010

Purpose Early detection of ovarian cancer has great promise to improve clinical outcome. Patients and Methods Ninety-six serum biomarkers were analyzed in sera from healthy women and from patients with ovarian cancer, benign pelvic tumors, and breast, colorectal, and lung cancers, using multiplex xMAP bead-based immunoassays. A Metropolis algorithm with Monte Carlo simulation (MMC) was used for analysis of the data. Results A training set, including sera from 139 patients with early-stage ovarian cancer, 149 patients with late-stage ovarian cancer, and 1,102 healthy women, was analyzed with MMC algorithm and cross validation to identify an optimal biomarker panel discriminating early-stage cancer from healthy controls. The four-biomarker panel providing the highest diagnostic power of 86% sensitivity (SN) for early-stage and 93% SN for late-stage ovarian cancer at 98% specificity (SP) was comprised of CA-125, HE4, CEA, and VCAM-1. This model was applied to an independent blinded validation set consisting of sera from 44 patients with early-stage ovarian cancer, 124 patients with late-stage ovarian cancer, and 929 healthy women, providing unbiased estimates of 86% SN for stage I and II and 95% SN for stage III and IV disease at 98% SP. This panel was selective for ovarian cancer showing SN of 33% for benign pelvic disease, SN of 6% for breast cancer, SN of 0% for colorectal cancer, and SN of 36% for lung cancer. Conclusion A panel of CA-125, HE4, CEA, and VCAM-1, after additional validation, could serve as an initial stage in a screening strategy for epithelial ovarian cancer.
Rituximab and Subcutaneous 2-Chloro-2′-Deoxyadenosine Combination Treatment for Patients With Waldenström Macroglobulinemia: Clinical and Biologic Results of a Phase II Multicenter Study
Authors: Laszlo Daniele , Andreola Giovanna , Rigacci Luigi , Fabbri Alberto , Rabascio Cristina , Mancuso Patrizia , Pruneri Giancarlo , Radice Davide , Pinto Antonello , Frigeri Ferdinando , Calabrese Liliana , Billio Atto , Bertolini Francesco , Martinelli Giovanni 
Published: April 2010

Purpose To assess the efficacy of 2-chloro-2′-deoxyadenosine (2-CdA) given subcutaneously (SC) in combination with rituximab in the treatment of newly diagnosed/pretreated patients with Waldenström macroglobulinemia (WM) and to correlate the response to treatment with biologic findings (immunophenotypic and pharmacogenomic analysis). Patients and Methods From December 2003 to February 2007, 29 patients were enrolled. Intended therapy consisted of a combination of rituximab (375 mg/m2) on day 1 followed by 2-CdA 0.1 mg/kg (SC injection) for 5 consecutive days, administered monthly for four cycles. Anemia (n = 16), neurologic symptoms (n = 6), symptomatic cryoglobulinemia (n = 4), and thrombocytopenia (n = 3) represented the reasons for starting treatment. The expression of ζ chain–associated protein kinase 70 (Zap-70) and of seven genes involved in 2-CdA metabolism as markers of response to the combination treatment was evaluated. Results With a median follow-up of 43 months, the overall response rate observed was 89.6%, with seven complete responses (CR), 16 partial responses, and three minor response, without any difference between newly or pretreated patients (P = .522). The therapy was well tolerated, except for transitory cardiac toxicity (n = 2) and intolerance to rituximab (n = 2). No major infections were observed despite the lack of antimicrobial prophylaxis. No patients developed transformation to high-grade non-Hodgkin's lymphoma nor myelodysplasia. Low expression levels of human concentrative nucleoside transporter 1 (hCNT1) were correlated with the failure to achieve a CR (P = .024), whereas no association with Zap-70 expression was found. Conclusion The combination of rituximab and SC 2-CdA is safe and effective in patients with WM requiring treatment. The pharmacogenomic analysis associated with the study suggests hCNT1 might be beneficial in predicting clinical response to such a combination treatment.
Testis Cancer Survivors' Health Behaviors: Comparison With Age-Matched Relative and Demographically Matched Population Controls
Authors: Shinn Eileen H. , Swartz Richard J. , Thornton Bob B. , Spiess Philippe E. , Pisters Louis L. , Basen-Engquist Karen M. 
Published: April 2010

Purpose To determine the prevalence rate of health behaviors in testis cancer survivors and to determine whether the rate of health behaviors in survivors was significantly different than those of their age-matched relative controls and a population-based control group matched for age, sex, education, and income. Patients and Methods The health behaviors of 162 testis cancer survivors were compared with their age-matched relative controls (n = 74) and an age-, sex-, education-, and income-matched population-based control group (n ranged from 1,123 to 9,775). Health behaviors were assessed with the telephone-administered Behavioral Risk Factor and Surveillance Survey. Results Nearly one in five testis cancer survivors reported current smoking and one third reported problem drinking. Only 11% reported having at least five servings of fruits and vegetables per day. Compared with their relative controls, the survivors were more likely to engage in regular exercise. For those participants who drank, survivors were twice as likely to engage in problem drinking and averaged a higher number of drinks compared to their Centers for Disease Control (CDC) controls. Survivors were also half as likely to have at least five servings of fruits and vegetables per day compared with the CDC controls. Conclusion The overall picture regarding testis cancer survivors' health behaviors was mixed compared with the relative and CDC control groups. Our results suggest that reduced alcohol use and increased fruit and vegetable consumption may be important targets for future disease prevention in testis cancer survivors.
Population-Based Study of the Risk of Second Primary Contralateral Breast Cancer Associated With Carrying a Mutation inBRCA1orBRCA2
Authors: Malone Kathleen E. , Begg Colin B. , Haile Robert W. , Borg Ake , Concannon Patrick , Tellhed Lina , Xue Shanyan , Teraoka Sharon , Bernstein Leslie , Capanu Marinela , Reiner Anne S. , Riedel Elyn R. , Thomas Duncan C. , Mellemkjær Lene , Lynch Charles F. , Boice John D. , Anton-Culver Hoda , Bernstein Jonine L. 
Published: April 2010

PurposeWomen with breast cancer diagnosed early in life comprise a substantial portion of those tested for BRCA1/BRCA2 mutations; however, little information is available on the subsequent risks of contralateral breast cancer in mutation carriers. This study assessed the risk of subsequent contralateral breast cancer associated with carrying a BRCA1 or BRCA2 mutation.Patients and MethodsIn this nested case-control study, patients with contralateral breast cancer diagnosed 1 year or more after a first primary breast cancer (n = 705) and controls with unilateral breast cancer (n = 1,398) were ascertained from an underlying population-based cohort of 52,536 women diagnosed with a first invasive breast cancer before age 55 years. Interviews and medical record reviews were used to collect risk factor and treatment histories. All women were tested for BRCA1/BRCA2 mutations. Relative (rate ratios) and absolute (5- and 10-year cumulative) risks of developing contralateral breast cancer following a first invasive breast cancer were computed.ResultsCompared with noncarriers, BRCA1 and BRCA2 mutation carriers had 4.5-fold (95% CI, 2.8- to 7.1-fold) and 3.4-fold (95% CI, 2.0- to 5.8-fold) increased risks of contralateral breast cancer, respectively. The relative risk of contralateral breast cancer for BRCA1 mutation carriers increased as age of first diagnosis decreased. Age-specific cumulative risks are provided for clinical guidance.ConclusionThe risks of subsequent contralateral breast cancer are substantial for women who carry a BRCA1/BRCA2 mutation. These findings have important clinical relevance regarding the assessment of BRCA1/BRCA2 status in patients with breast cancer and the counseling and clinical management of patients found to carry a mutation.
High-Dose Therapy and Autologous Stem-Cell Transplantation in Waldenström Macroglobulinemia: The Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
Authors: Kyriakou Charalampia , Canals Carmen , Sibon David , Cahn Jean Yves , Kazmi Majid , Arcese William , Kolbe Karin , Gorin Norbert Claude , Thomson Kristy , Milpied Noel , Niederwieser Dietger , Indrák Karel , Corradini Paolo , Sureda Anna , Schmitz Norbert 
Published: April 2010

Purpose The role of autologous stem-cell transplantation (ASCT) in Waldenström macroglobulinemia (WM) is not defined. The aim of this study was to analyze the results of ASCT in patients with WM and to determine the prognostic factors that have a significant impact on outcome. Patients and Methods We analyzed 158 adult patients with WM reported to the European Group for Blood and Marrow Transplantation (EBMT) between January 1991 and December 2005. Median time from diagnosis to ASCT was 1.7 years (range, 0.3 to 20.3 years), 32% of the patients experienced treatment failure with at least three lines of therapy, and 93% had sensitive disease at the time of ASCT. Conditioning regimen was total-body irradiation–based in 45 patients. Median follow-up for surviving patients was 4.2 years (range, 0.5 to 14.8 years). Results Nonrelapse mortality was 3.8% at 1 year. Ten patients developed a secondary malignancy, with a cumulative incidence of 8.4% at 5 years. Relapse rate was 52.1% at 5 years. Progression-free survival (PFS) and overall survival were 39.7% and 68.5%, respectively, at 5 years and were significantly influenced by number of lines of therapy and chemorefractoriness at ASCT. The achievement of a negative immunofixation after ASCT had a positive impact on PFS after ASCT. When used as consolidation at first response, ASCT provided a PFS of 44% at 5 years. Conclusion ASCT is a feasible procedure in young patients with advanced WM. ASCT should not be offered to patients with chemoresistant disease and to those who received more than three lines of therapy.