bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Birthweight and Maternal Fertility Problems with Childhood Cancers.
Authors: Dorak M. Tevfik , Hammal Donna M. , Pearce Mark S. , McNally Richard J.Q. , Parker Louise 
Published: October 2019

Abstract
Higher birthweight, maternal history of miscarriage and low birth order have been associated with increased risk of childhood leukaemias and some solid tumours. No study has investigated these factors together and differences in disease etiology between girls and boys have been generally overlooked. In a retrospective case-control study, 732 childhood (≤15 yr) cancer cases from the population-based Northern Region Young Persons’ Malignant Disease Registry (NRYPMDR) whose hospital birth records could be accessed and 3723 controls matched for date and hospital of birth were compared. We examined maternal reproductive history and birthweight for gender-specific associations using conditional logistic regression. In univariate analysis, maternal history of miscarriage showed an association with all cancers (OR = 1.29; 95% CI = 1.05 to 1.62, P = 0.02). In individual cancer groups, this association was significant for acute lymphoblastic leukaemia (ALL) (n=225, OR = 1.56; 95% CI = 1.07 to 2.27, P = 0.02), and marginally significant in osteosarcoma and neuroblastic tumours (neuroblastoma and ganglioneuroblastoma). There was no significant association with birth order. Being first born was a weak risk factor for ALL in boys only (OR=1.3, 95% CI = 0.8 to1.8). In boys but not in girls, the risk of ALL increased with birthweight (OR = 1.06 per 100 gr increase; 95% CI = 1.01 to 1.11, P = 0.01). When birthweights were normalized using UK standards for gestational age and gender, the associations were not more marked. A multivariate model for ALL confirmed the independence of associations with miscarriage history and birthweight. Gestational age was not a risk marker and did not explain the associations with birth weight and miscarriage history. Consideration of gender unravelled significant associations of maternal reproductive history and size at birth with childhood cancer markedly different between girls and boys. Most notably, associations with birth weight and miscarriage and the weak association with being first-born in childhood ALL were all stronger in males. The findings for birthweights normalized for gestational age suggested that size at birth rather than in utero growth trajectory is of etiologic importance in childhood ALL.
Epidemiology of Fungal Infections in Hematological Malignancies in Italy: SEIFEM-2004 Study (Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne).
Authors: Pagano Livio , Caira Morena , Candoni Anna , Offidani Massimo , Martino Bruno , Liso Vincenzo , Picardi Marco , Bonini Alessandro , Chierichini Anna , Fanci Rossella , Caramatti Cecilia , Invernizzi Rosangela , Gallamini Andrea , Mitra Maria Enza , Melillo Lorella , Allione Bernardino , Fianchi Luana , Falcucci Paolo , Valentini Caterina Giovanna , Van Lint Maria Teresa , Girmenia Corrado , Nosari Anna Maria 
Published: October 2019

Abstract
Background: To evaluate the incidence and the outcome of fungal infections in patients (pts) affected by hematological malignancies (HM).
Methods: A retrospective study, conducted over 1999–2003, in pts with HM, admitted in 18 Italian Hematology divisions in tertiary cares or university hospitals, who developed proven or probable fungal infections.
Results: The population included 11,802 pts: 3,012 AML (25.5%), 1,173 ALL (9.9%), 596 CML (5%), 1,104 CLL (9.4%), 1,616 MM (13.7%), 3,457 NHL (29.3%), 844 HL (7.2%). Pts who underwent HSCT were included in a different analysis. A fungal infection occurred in 538 pts, with an incidence of 4.6%; in particular we registered 346 episodes sustained by moulds (incidence 2.9%) and 193 by yeasts (1.6%). The incidence rate depends upon underlying malignancy (12.3% in AML, 6.5% in ALL, 2.7% in CML, 0.6% in CLL, 0.5% in MM, 1.6% in NHL, 0.9% in HL). Among moulds, the etiological agents were Aspergillus (310 episodes, incidence 2.8%), Mucorales (13 pts, 0.1%), Fusarium (15 pts, 0.1%), and other rare fungi (7 pts, 0.1%). Among yeasts we registered septicemia due to Candida (175 pts, 1.6%). Other yeast infections were caused by Cryptococcus (8 pts, 0.1%), Tricosporon (7 pts, 0.1%) and other rare agents (2 pts). We did not observed an increase of A.terreus infections while the number of episodes sustained by A.flavus increased from 1999 to 2003 (RR 2.10; IC95% 0.8–5.49; p-value 0.117). The overall mortality rate was 1.8%. Among 538 pts with fungal infection 39% died for this complication, with differences between aspergillosis (42%), zygomycosis (63%), fusariosis (53%) and candidemia (33%). There was not variation in mortality rate during the study period; comparing these pts with those observed in our previous studies during the period 1987–1988 we observed a significant reduction of death due to aspergillosis (RR 1.90; IC 95% 1.17–3.09), but no differences in mortality rate due to Candida.
Conclusions: Our study confirms the general trends already described: infections due to moulds are more frequent than those caused by yeast. Aspergillus remains the main etiologic agent, followed by Candida. The other agents (Mucorales, Fusarium, Trichosporon) remain rare. AML represents the most frequently involved category. The mortality rate due to aspergillosis is actually about 40%, with a remarkable decrease when compared to past years; as for candidemia, we observed a reduction in the incidence, but not in the mortality rate.
Clinical Significance of the Philadelphia Chromosome Positive Pediatric Acute Lymphoblastic Leukemia in Chinese.
Authors: Ye Qidong , Gu Long-Jun , Tang JingYan , Xue Huiliang , Chen Jing , Pan Ci , Chen Jing 
Published: October 2019

Abstract
Objective To explore the incidence, clinical characteristics and prognosis of childhood acute lymphoblastic leukemia (ALL) with t(9; 22).
Methods All of the clinical characteristics of the 325 childhood ALL patients from November, 1998 to November, 2003 were analysised. The statistics was done by SPSS 10.0.
Results There were 129 cases of high-risk ALLs in 325 Childhood ALL patients, with 95 males and 34 females. BCR-ABL fusion gene was found in 16 cases by RT-PCR, accounting for 4.9%. All of them were m-BCR-ABL. There were 12 males and 4 females among 16 Ph positive ALLs. The mean age at diagnosis was 8.54±3.36 (3.5 to 12.5) years, 50.0% of which were older than 10 years. The percents of patients who had initial WBC count more than 100×109/L, myeloid antigen coexpression, hypodiploidy, and ALL-L2 were 37.5%, 53.8%, 33.3%, and 62.5%, respectively. By comparison, the percents of age (older than 10 years), initial WBC count (more than 100×109/L), myeloid antigen coexpression, prednisone poor response (PPR), and CR over 35 days in the Ph positive ALLs were higher than that in the negative ALLs. No statistic difference was found in sex and L2 proportion between them. Moreover, no difference was found between Ph positive ALLs and negative high-risk ALLs in the mentioned parameters, except for the myeloid antigen coexpression. Four-year event-free survivals (EFS) and disease-free survivals (DFS) were 77.4% and 79.4, respectively, in Ph negative ALLs, but were 33.0% and 47.7%, respectively, in Ph positive ALLs (P<0.01). In Ph negative high-risk ALLs, the four-year EFS and DFS were 51.2% and 54.6%, respectively, both of which had no statistic difference between Ph positive cases. Only one Ph positive child received allogeneic BM transplantation, who remained in EFS at the time of this analysis.
Conclusion The percent of t(9; 22) in Chinese childhood ALLs had no difference with the report abroad. There were statistic differences between Ph positive and negative childhood ALLs in age, initial WBC count, early response to therapy, and four-year EFS and DFS, but no difference was found between Ph positive ALLs and Ph negative high-risk ALLs, except for the immunophnotype. Aggressive treatment, such as high-dose chemotherapy with allogeneic BM transplantation should be considered for these patients to improve survival.
Event-free survival curves for children with acute lymphoblastic leukemia Event-free survival curves for children with acute lymphoblastic leukemia
Efficacy of Chemotherapy Regimen Containing Pirarubicin on 111 Patients with High-Risk, Relapse and Refractory Acute Leukemia.
Authors: Huang Fen , Meng Fan Yi 
Published: October 2019

Abstract
Objective: To evaluate the efficacy of chemotherapy regimen containing pirarubicin on the patients with high-risk, relapse and refractory acute leukemia.
Methods: 184 patients with high-risk, relapse and refractory acute leukemia were recruited and randomized to experiment group (111) and control group (73). The experiment group included 64 acute non-lymphocytic leukemia (ANLL) patients, 39 acute lymphocytic leukemia (ALL) patients and 8 mixed leukemia patients, and all received one of the following regimen: TA, VTP, VTLP or TAVP (T: pirarubicin, V: vincristine, P: prednisone, L: L-asparaginase). The patients in the control group received routine chemotherapy without pirarubicin.
Results: the complete remission rate (CR) was significantly higher in pirarubicin-treated group than in control group either for all the patients (64.4% vs 43.8%, p<0.05) or for ANLL patients (68.1% vs 36.2%, p<0.05). At the same time bone marrow suppression was severer in pirarubicin-treated group than in control group (p<0.05).
Conclusions: chemotherapy regimen containing pirarubicin is more effective than routine regimen without pirarubicin in the management of high-risk, relapse and refractory acute leukemia, especially in ANLL patients, although it induce severer but tolerable bone marrow suppression.
sVEGFR3 but Not VEGF-C Plasma Level Is Increased in Non-Hodgkin Lymphoma.
Authors: Wrobel Tomasz , Mazur Grzegorz , Biedron Monika , Jazwiec Bozena , Pyszel Angelika , Kuliczkowski Kazimierz 
Published: October 2019

Abstract
BACKGROUND: Non-Hodgkin’s lymphomas (nHL) may spread via blood vasculature or lymphatics. Vascular endothelial growth factor (VEGFs) family of glycoproteins is essential for angiogenesis and lymphangiogenesis. VEGF-C enhances lymphangiogenesis and promotes metastasis via lymphatic vessels. VEGF-C stimulates lymphangiogenesis by binding VEGFR-2 and VEGFR-3 receptors on lymphatic endothelial cells Elevated serum levels of proangiogenic cytokines (i.e. VEGF) are the independent prognostic factor in nHL. Data concerning the role of lymphangiogenesis in nHL are very limited. Salven et al. showed low VEGF -C mRNA in lymphoma cells. The role of lymphangiogenesis in lymphoma dissemination remains to be determined. The aim of the study was to assess plasma levels of VEGF-C and sVEGFR3 in nHL patients. before chemotherapy and after achieving complete remission (CR).
MATERIAL AND METHODS: Plasma samples from 39 adult (18 females and 21 males) patients with B-cell nHL taken at diagnosis and in CR were measured by ELISA to evaluate VEGF-C and sVEGFR-3 levels (Bender Medsystems and R&D Systems respectively). In addition plasma samples from 25 healthy volunteers were evaluated as the control. Statistical analysis was performed using U Mann-Whitney test (p<0,05).
RESULTS: There was no significant differences in VEGF-C levels between untreated nHL group, nHL in CR and the control (166,9±221,8 vs 217±294,4 vs 161,2±118 pg/ml respectively). In untreated nHL patients sVEGFR3 level was significantly higher than in the control (19434±8990 vs 13949±5417 pg/ml respectively; p=0,007). In CR sVEGFR3 decreased but was still significantly higher than in healthy control (18163±9108 vs 13949±5417 pg/ml respectively; p=0,038).
CONCLUSION: Similarly to previous studies we demonstrated that VEGF-C plasma levels were not increased in nHL. There are several observation that in human tumors VEGFR3 is involved both in lymphangiogenesis and angiogenesis. Increased VEGFR3 in nHL may reflect intensity of blood and lymphatic endothelium proliferation.
Expression of VEGF-C and Its Receptor VEGFR-3 in Diffuse Large B-Cell Lymphomas.
Authors: Pazgal Idit , Boycov Olga , Shpilberg Ofer , Okon E. , Bairey Osnat 
Published: October 2019

Abstract
Vascular endothelial growth factor (VEGF)-C and its receptor tyrosine kinase VEGFR-3 are critical regulators of lymphangiogenesis. Their expression has been observed in a variety of solid tumors and was associated with lymph node metastasis in patients. The aim of this study was to evaluate whether aggressive lymphatic malignant cells express VEGF-C and its receptor VEGFR-3 and whether the expression correlates with intratumoral microvessel density, and patient outcome. Pathological specimens were taken at diagnosis from 29 diffuse large B-cell lymphoma (DLBCL) patients (11 men, 18 females, mean age 70 years) who were diagnosed between the years 1997–2001. The specimens were evaluated by immunohistochemical staining to determine the expression of VEGF-C and VEGFR-3 and the microvessel count (by factor-VIII-related antigen). All lymphoma specimens demonstrated positive staining for VEGF-C and VEGFR-3 with high intensity staining in 50% and 68% of the specimens respectively. The mean microvessel count was 58 (range 23–120) and blood vessels in all specimens demonstrating positive staining for both VEGF-C and VEGFR-3 (strong in 25% and 58% respectively). We found a significant correlation between high serum levels of β2 microglobulin and high VEGFR-3 staining. High intensity staining was found in 77% of the patients with high β2 microglobulin compared to 44% of the patients with normal β2 microglobulin level (p=0.03).
The patients who expressed high intensity VEGFR-3 staining had worse survival. In the 13 patients who lived more than 5 years, only 46% of them demonstrated high intensity staining while 85% of patients that lived less than 5 years demonstrated such staining (p=0.01). The median event free survival (EFS) was 21 months. A significantly higher proportion of the patients with low EFS (lower than 21 months) demonstrated high intensity staining for VEGFR-3, (p=0.01)
These results suggest that DLBCL tumors express both VEGF-C and its receptor (VEGFR-3) and that this signaling pathway may be associated with patient’s prognosis.
Figure Figure
Identification of Subtype-Specific Genomic Alterations of Acute and Lymphoma Types of Adult T-Cell Leukemia/Lymphoma.
Authors: Oshiro Aya , Tagawa Hiroyuki , Oshima Kouichi , Karube Kennosuke , Uike Naokuni , Tashiro Yukie , Utsunomiya Atae , Masuda Masato , Morishima Yasuo , Nakamura Shigeo , Seto Masao 
Published: October 2019

Abstract
Background: Adult T cell leukemia/lymphoma (ATLL) is a human T-lymphotropic virus type-I mediated neoplasm and four major clinical subtypes are recognized; i.e., smoldering, chronic, lymphoma and acute types. Among these subtypes, acute and lymphoma types are fetal disease with poor prognosis. Although these two subtypes represent different clinical features, detailed analysis for genomic/genetic differences has not been sufficiently investigated.
Purpose: To investigate genomic aberrations of these subtypes, we performed array-based comparative genomic hybridization (array CGH: 2308 BAC clones spotted in duplicate) for 66 cases of ATLL (17 cases of acute and 49 cases of lymphoma subtypes). To determine target genes in recurrently amplified regions, quantitative real-time PCR (RQ-PCR) was conducted.
Results: Array CGH: Comparison of genome profiles revealed that lymphoma type shows more frequent gain and loss than those of acute type. The numbers of respective genomic gain and loss regions of lymphoma type were 9.7 and 9.8 on average. The numbers of genomic gain and loss regions of acute type were 4.2 and 4.5 on average. Gain of 1q, 2p, 4q, 7p and 7q, and loss of 10p, 13q, 16q and 18p were characteristic to lymphoma type whereas gain of 3p and 3q was specific to acute type. Recurrent high-level amplifications were found at 1p35, 6p25, 7p22.2, 7q21–q22, 7q31–q36 and 14q32 in lymphoma type. However, such genomic amplifications were not found in acute type.
RQ-PCR: CARMA1 (7p22 locus), which encodes signaling proteins associated with development of B and T cells, was a possible target of the 7p22 amplification in lymphoma type. The extremely higher expression of BCL11B (14q32 locus) which is a key regulator of both differentiation and survival during thymocyte development, was found in acute type irrespective of the 14q32 amplification. However, no overexpression of BCL11B was found in lymphoma type with high copy number gain, indicating that BCL11B is not the target gene for 14q32 amplification in the lymphoma type.
Conclusion: Array-CGH revealed that patterns of genomic aberrations between acute and lymphoma types were different. Quantitative gene expression analysis also implicated distinct mechanism of aberrant gene expressions between acute and lymphoma types. Combination of array-CGH and quantitative gene expression analysis provided evidence that the acute and lymphoma types are developed via distinct genomic/genetic pathways.
A Pilot Study of Physical Activity Level and Mood among Long-Term Lymphoma Survivors.
Authors: Habermann Thomas M. , Janney Carol A. , Clark Matthew M. , Rummans Teresa A. , Sloan Jeff S. , Cerhan James R. , Geyer Susan M. , Thomas Randall J. 
Published: October 2019

Abstract
It has been well-documented in cardiac patients and in the general population that physical activity improves physical and mental health. Physical activity could also improve the health and quality of life of long-term lymphoma survivors, but little is known about physical activity in this group of patients. Using the Mayo Tumor Registry, we identified eligible patients who were 16 years or older at diagnosis, U.S. residents, first diagnosed with Hodgkin or non-Hodgkin lymphoma from 1984–1998, diagnosed and/or initially treated at Mayo Clinic Rochester, and survived for 5 to 20 years (N=2,485). In October of 2004, we mailed a 23-page survey to 95 randomly selected patients; 7 were found to be ineligible (deceased or too ill). Of the 88 remaining patients, we were able to find a correct address for 82, and 57 completed a survey for a 70% participation rate. Physical activity was self-reported using the Godin (1985) Leisure-Time Exercise Questionnaire. Of the 54 patients with complete data for this report, the mean age at completion of the questionnaire was 60.8 years (26.1–86.7). The mean time since diagnosis was 12.0 years (6.3–19.9), and 52% survived more than 11 years. The histologies included 22 (39%) Hodgkin lymphoma, 21 (38%) diffuse large B-cell lymphoma, 3 (5%) follicular lymphomas, 1 (2%) high-grade lymphoma, 5 (9%) peripheral T-cell lymphomas, and 4 (7%) other. Regular fitness was reported by 21% of the respondents. This is lower than a recent report of adults aged 50 years and older, where approximately 40% of those free of chronic disability were attaining recommended daily physical activity levels. It is also lower than the expected 30% in patients with disabilities from the Behavioral Risk Factor Survey (Brown DR et al., Med Sci Sports Exerc2005;37:620–9). In addition, although not statistically significant, there were effect sizes observed suggesting that sedentary responders had higher levels of depression, higher anxiety levels, more distress, and lower quality of life (QOL) compared to physically active respondents. These finding need to be verified in a larger sample to obtain better estimates. In conclusion, levels of physical activity were lower than general population samples. These results also suggest that physical activity level may be related to improved mood and QOL in this population.
A Novel Functional Role for Soluble CD27 in the Pathogenesis of Waldenstrom’s Macroglobulinemia.
Authors: Ho Allen W. , Leleu Xavier , Hatjiharissi Evdoxia , Tournilhac Olivier , Xu Lian , O’Connor Kelly , Manning Robert , Santos Daniel , Chemaly Mariana , Branagan Andrew , Hunter Zachary , Patterson Christopher , Anderson Kenneth C. , Treon Steven P. 
Published: October 2019

Abstract
The tumor necrosis factor (TNF) receptor family member, CD27, is a transmembrane co-stimulatory molecule present on primed T and B lymphocytes that also secrete a soluble form (sCD27). Recent evidence has suggested that interactions between CD27 and its TNF-like ligand, CD70, play a critical role in regulating B-cell activation and survival, though the detailed mechanism(s) by which this occurs remain unclear. Waldenstrom’s Macroglobulinemia (WM) represents a lymphoplasmacytic lymphoma characterized by a monoclonal IgM gammopathy and possesses a mast cell component that may contribute to its pathogenesis (Blood 104; 646a). Using ELISA assays, we observed that WM patients displayed significantly higher levels of sCD27 in their sera (median 7.45, range 0–19.42 U/ml) versus healthy donors (median 0, range 0–2.78 U/ml; p=2.5 x 10−7). CD27 was expressed in 7/7 patients using RT-PCR analysis, but was expressed on the cell surface of tumor cells in 5/12 patients using flow cytometric analysis. Conversely, CD70 expression was widely expressed on both tumor cells (6/6 patients) and mast cells (10/11 patients) using flow cytometric analysis. In order to define the functional role of sCD27 in WM, we cultured BCWM.1 (CD27−CD70+) WM cells, and LAD1 (CD27−CD70+) mast cells with sCD27 (0.1–50 ug/mL), and observed no effect on proliferation or induction of apoptosis. Culture of LAD1 cells with sCD27 did, however, result in marked upregulation of the TNF family ligands CD40L (CD154) and a proliferation induction ligand (APRIL), which previous work in our laboratory had implicated as mast cell proliferation and survival factors in WM. Taken together, these studies suggest a novel functional role for sCD27, and imply a pivotal role in the pathogenesis of WM.