bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Declining Risk of ABO Incompatibilities: Twelve Years of Hemovigilance in France.
Authors: Renaudier Philippe , Mai Mai Phuong Vo , Schlanger Sylvie , Ounnoughene Nadra , Breton Pascal , Cheze Stephane , Girard Albane , Hauser Lisette , Legras Jean Francois , Rebibo Danielle , Waller Chantal , Lassale Bernard , Caldani Cyril 
Published: October 2019

Abstract
Background: ABO incompatibilities (ABOi) usually result from the failure to comply with Standard Operating Procedures (SOP). Continuous training (CT) is the main way to ensure their proper use in ultra-high security systems like civil aviation but little is known for transfusion. In France, SOP include a Beth-Vincent test at the bedside before the transfusion of Packed Red Cells (PRC). At the hospitals, Hemovigilance Officers (HO) are in charge of transfusion safety along with the settlement of traceability and the notification of all Adverse Effects (AE). If SOP and CT are requested by Law since 1993 for blood banks, they are only advised for hospitals even though the bedside Beth-Vincent test requires a special training. However, HO have more and more transposed the model of blood banks in hospitals especially since 2000. Objective: to describe time-trends of ABOi observed in e-fit, the French Hemovigilance database. Population and methods: All AE with “acute ABOi” as the final diagnostic were considered. Time-trends were studied according to the Box and Jenkins model (ARMA).
Results: From 07/01/1994 to 12/31/2005, 79 106 AE were registered in e-fit, corresponding to about 30,000,000 Labile Blood Products (LBP) transfused. 304 (0.4%) were ABOi (1/107,850 LBP transfused). There were 183 men and 121 women with 81.3% of whom more than 40 years old. 205 patients (67.4%) received only PRC, 73 (24.0%) Platelet Concentrates (PC), 22 (7.2%) Fresh Frozen Plasma (FFP) and 4 (1.3%) more than a single LBP. 18 ABOi were fatal, possibly (4 cases) probably (4 cases) or definitely (9 cases) associated with a PRC, and 1 doubtfully with a FFP. Time-trends displayed 3 periods: (1) from 1994 to 1997 ABOi increased concurrently with the frequency of all AE notifications, (2) from 1997 to 2000 they reached a steady-state with 35 ABOi/year on average (1/70,000 LBP), (3) since 2001 they regularly decreased of 14%/year on average (13 ABOi for 2005 = 1/198,450 LBP). The localization of the failure to comply with SOP (i.e. hospital, blood bank or both) was studied for PRC. From 1997 to 2005, the liability of blood banks alone or along with hospitals remained stable (resp 0.42 and 2.58/year on average) whereas those of hospitals dramatically decreased (16.25/year from 1997 to 2000 and 8.6/year from 2001 to 2005).
Conclusion: (1) ABOi are now 3 times less frequent than in 2000 ; (2) a notification bias is unlikely because both hospitals and blood banks are aware of traceability data that include the ABO phenotype for both the recipient and the LBP issued ; (3) CT applied on a nationwide basis seems to be the main factor to reduce ABOi in hospitals ; (4) a residual risk related to human errors seems to exist ; (5) the way to overcome that risk remains a matter of debate.
Sistematic Analysis of ABO Gene in A3 and A3B Individuals Reveals New ABO Variants.
Authors: Domingues Alexandre E. , Novaretti Marcia C.Z. , Dorlhiac-Llacer Pedro E. , Chamone Dalton A.F. 
Published: October 2019

Abstract
BACKGROUND: In addition to the common ABO phenotypes, numerous phenotypes with a weak expression of the A or B antigens on red blood cells have been found. DNA genotyping on A3 e A3B subgroups has been performed in small number of samples, mainly in family studies. To date, seven ABO alleles have been associated to A3 and A3B subgroups (ABO*A301 to ABO*A307) revealing molecular heterogeneity. Our purpose was to study molecular events on exon 7 of ABO gene in 100 A3 and A3 B blood donors samples.
STUDY DESIGN AND METHODS: ABO serologic analyses of 12,283 blood donors of blood groups A and AB allowed the detection of 13 A3 and 87 A3B samples. Initially, DNA amplification was performed using sequence specific polymerase chain reaction (PCR-SSP) to identify 467C>T, 829G>A, 871G>A and 1060delC polimorphisms of exon 7 of ABO gene, followed by direct DNA sequencing.
RESULTS: New ABO variants were detected in 5/13 (38.5%) of A3 and in 38/87 (43.7%) of A3B samples. ABO*A302/ABO*A301 genotype was found in 30.7% A3 and, ABO*A302/ABO*B104 in 17.1% of A3B samples. The 871G>A mutation previously reported only in A3B individuals was found in 9 blood samples tested as A3 in our study. For the first time, mutations between 441–450 nucleotides of exon 7 of ABO gene was detected in 39 samples (single nucleotide polimorphisms and deletions) of A3 and A3B subgroups.
CONCLUSION: This is the first large molecular study of A3 and A3B samples. Sistematic analysis of A3 and A3B samples reveals new ABO variants caused by different molecular events. Mutations between 441 and 450 nt. of exon 7 are critical for transferase A expression in individuals typed as A3 and A3B.
Rapid Duffy Genotyping in Sickle Cell Disease Patients Using PCR-SSP Is a Valuable Tool for Blood Component Selection.
Authors: Novaretti Marcia C.Z. , Bonifacio Silvia L. , Medeiros Vitor R. , Gualandro Sandra F.M. , Dorlhiac-Llacer Pedro E. , Chamone Dalton A.F. 
Published: October 2019

Abstract
Background: Sickle cell disease (SCD) patients are frequently transfused and, finding adequate and safe blood component for them has a great impact in transfusion services and in patients clinical follow-up. DNA genotyping for RBC antigens is a tool for the management of these patients to overcome the limitations of hemagglutination assays. However, the polymerase chain reaction (PCR) by restriction fragment length polymorphism (RFLP) is time consuming. The aim of this study was to develop a rapid PCR specific sequence primer (SSP) approach for Duffy genotyping in SCD patients.
STUDY DESIGN AND METHODS: Blood samples from 91 SCD patients were studied by hemagglutination and by PCR-SSP for Duffy system. All samples typed as Fy(b-) were submitted to adsorption and elution techniques to detect the weak expression of Fyb antigen. DNA was extracted by a commercial DNA extraction kit (QIAamp DNA, QIAGEN, Germany). Detection of FY*A, FY*B, FY*B-33, FY*B-265T and FY*B-298A were performed using specific primers by PCR-SSP. DNA amplification was carried out in a final volume of 20μL with identical reaction mixture and cycling conditions as follows: 0.2μg of genomic DNA, 0.2mM of each dNTP, 5% of glycerol, 1.5 units of platinum Taq polymerase (Invitrogen, Brazil) in the buffer supplied, 5.0mM of MgCl2 and 10.0 pmoles of each primer. PCR fragments were separated for 90 minutes at 100V using 0.5μg.mL-1 ethidium bromide-stained 2.0% agarose gel and visualized in a UV light apparatus (Eagle Eye II, EUA).
Results: Table 1 shows the results of Duffy phenotyping, Duffy genotyping and gene frequencies in SCD patients The most common phenotype found in our study was Fy(a–b+), 35.2%. In three samples (3.3%) we detected weak Fyb antigen and identified FY*B-265T alelle. All samples phenotyped as Fy(a–b–) genotyped as (FYB-33/FYB-33).
CONCLUSION: PCR-SSP is a method that contributes for easily and accurate Duffy genotyping for SCD patients. In our study, all SCD patients with Fy(a–b–) can be safely transfused with Fy(b+) red blood cell components with no risk for developing anti-Fyb saving rare Fy(a–b–) units.
Table 1 Phenotype Genotype n Genotype Frequency Fy(a+b+) FYA/FYB 16 0.176 Fy(a–b+) FYB/FYB 23 0.253 FYB/FYB-265T 9 0.099 Fy(a+b–) FYA/FYA 18 0.198 FYA/FYB-33 4 0.044 Fy(a–b–) FYB-33/FYB-33 21 0.231 TOTAL 91 1.00
Risk Factors for Blood Product Usage Following Sibling Allogeneic Haemopoietic Stem Cell Transplantation (allo-HCT).
Authors: Hurst Nicola , Mullighan Charles G. , Heatley Sue L. , Robinson Kathryn , Danner Silke , Hahn Uwe , Szer Jeff , Shuttleworth Peter , Hoyt Rosie , Schwarer Anthony P. , Muirhead Jenny , Bradstock Kenneth , Miller Lisa , Bardy Peter G. 
Published: October 2019

Abstract
Red cell and platelet transfusion requirements have been reported to be lower following reduced intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC allo-HCT) when compared to myeloablative (MA) allo-HCT. However, previous studies examined RIC regimens with lower haemopoietic toxicity than many of the regimens in use today. We investigated risk factors for red cell and platelet transfusion in patients enrolled prospectively in an Australian study investigating the non-HLA immunogenetics of sibling allo-HCT. The transfusion requirements in the first year post transplant were reviewed for 122 patients transplanted between 2002 and 2006 in three Australian transplant centres. Seventy-one patients received MA and 51 RIC regimens. Using regression analysis, the outcome variables of total red cell and platelet units transfused were analysed. The factors age, transplant centre, disease, transplant type (RIC v MA), days of neutropenia, death within 12 months, disease risk (high risk (HR) v standard risk (SR)) and ABO mismatch underwent univariate analysis. Associated variables with p<0.2 were included in a multivariable analysis. Duration of neutropenia, disease risk, death within 12 months and transplant centre were significantly associated with higher red cell and platelet usage (p<0.0001). Transplant type was not associated with transfusion requirement. Each additional day of neutropenia resulted in a 9% increase in number of red cell units transfused and 11% of platelet units. HR MA patients used an estimated 17 units of red cells compared to 12 units for SR. HR RIC patients used an estimated 26 units compared to 10 for SR RIC patients. HR patients used an estimated 16.9 platelet units compared to 8.5 for low risk. These data highlight the importance of disease risk and degree of myelosuppression as key risk factors for blood product usage following allo-HSCT.
Protein Tyrosine Phosphatase Receptor Type O (PTPRO) Exhibits Tumor Suppressor Properties in K562 Cells by Dephosphorylating Bcr-Abl.
Authors: Majumder Sarmila , Motiwala Tasneem , Ghoshal Kalpana , Kutay Huban , Datta Jharna , Lucas David , Byrd John C. , Jacob Samson T. 
Published: October 2019

Abstract
Regulation of protein phosphorylation by concerted action of protein kinases and phosphatases is important for normal physiological processes. Altered function or expression of one or more components of these regulatory molecules leads to many pathological conditions including cancer. We have previously shown that the truncated form of the receptor-type protein tyrosine phosphatase PTPROt predominantly expressed in haematopoietic cells is suppressed in Chronic Lymphocytic Leukemia (B-CLL). A direct correlation of CpG island methylation and reduced expression of the gene was observed in primary CLL samples and in several leukemia cell lines. To assess the functional significance of loss of PTPROt function in leukemia, we selected K562 cells as a model system, as PTPROt expression is silenced in these cells and is reactivated upon treatment with DNA hypomethylating agents. Ectopic expression of the catalytically active PTPROt inhibited growth of K562 cells and their clonogenic survival in soft agar (a characteristic of cancer cells). Further, cells expressing PTPROt exhibited delayed entry into S-phase from G0/G1 phase. Induction of apoptosis increased significantly in K562 cells expressing functional phosphatase upon serum withdrawal or exposure to the apoptogenic agent camptothecin. Tumorigenic potential of K562 cells in athymic nude mice was also significantly reduced upon ectopic expression of PTPROt. Finally, we demonstrate that the Bcr-Abl fusion protein, product of abnormal chromosomal translocation [t(9;22)] in chronic myelogenous leukemia, is a substrate of PTPROt. Tyrosine phosphorylation of this potent kinase was markedly reduced in K562 cells expressing the catalytically active PTPROt. Enhanced dephosphorylation of Bcr-Abl by PTPROt both in vivo and in vitro explains the observed phenotypes of the PTPROt expressing K562 cells. These data taken together delineate the molecular mechanism of tumor suppressor function of PTPROt in leukemic cells characterized by Philadelphia chromosome.
(This work was supported by a grant CA101956 from the National Institutes of Health).
Protein Disulfide Isomerase Is Required for Fibrin Generation and Platelet Thrombus Formation In Vivo.
Authors: Cho Jaehyung , Furie Barbara C. , Coughlin Shaun R. , Furie Bruce 
Published: October 2019

Abstract
Thiol isomerases catalyze disulfide oxidation, reduction and isomerization, playing an important role during protein synthesis. Recent studies suggest a role for protein disulfide isomerase (PDI), a prototype of the thiol isomerase family, in platelet function and regulation of tissue factor activity (Essex and Li. Curr Drug Targets. 2006; Chen and Hogg. J Thromb Haemost. 2006). To determine the role of intravascular PDI during thrombus formation, PDI expression, platelet accumulation, and fibrin generation were monitored following laser-induced arteriolar injury in the mouse cremaster muscle by intravital fluorescence microscopy. PDI antigen exhibited a time-dependent increase in the developing thrombus after vessel wall injury and remained associated with the thrombus. Infusion of bacitracin, a non-specific inhibitor of thiol isomerases, into the circulation inhibited platelet thrombus formation and fibrin generation in a dose-dependent manner. Infusion of a function-blocking monoclonal antibody to PDI (RL90) into the circulation of a wild type mouse also resulted in dose-dependent inhibition of platelet accumulation and fibrin generation. To determine whether PDI inhibits fibrin formation by blocking tissue factor activation, or by preventing platelet activation and the development of the membrane surface that is required for assembly of the tenase and the prothrombinase complex in vivo, we explored fibrin formation in mice lacking protease-activated receptor-4 (Par4). Although there is no stable accumulation of platelets and no platelet activation, fibrin formation is normal in the Par4 null mouse (Vandendries et al, Proc Natl Acad Sci USA. 2007), suggesting that fibrin generation in the laser-induced vessel injury model is independent of platelet activation. Infusion of the function-blocking anti-PDI antibody (RL90) into the circulation of a Par4 null mouse prior to vessel wall injury inhibited fibrin generation. These results indicate that PDI is required to generate tissue factor in a form that leads to thrombin generation and fibrin formation during thrombus development and is required for thrombus formation.
Study of NHEJ Function and Expression of Protein Ku70 in CML Patients.
Authors: Chen Pei-shuai , Fu Zheng-zheng , Cen Jian-nong , He Jun , Qiu Qiao-cheng , Yuan Xiao-ni , Chen Zi-xing 
Published: October 2019

Abstract
The abnormal activity of DNA repair after DNA double strand breakage results in genome instability. It is also thought that the malfunction in DNA repair may be involved in the generation of variety of chromosomal translocations in human leukemia. To investigate the relationship between the activity of DNA repairing by NHEJ and the expression of protein Ku70 in CML cells, the expression of protein Ku70 deprived from the chromatin was determined by Western Blot, using TBP(TATA Box Binding Protein)as the internal control, in bone marrow cells of CML patients as well as the normal controls. Our preliminary result showed that the gray ratios of Ku70 protein band over TBP band in 24 normal BM cells were 0 to 0.235, with a mean level of 0.0983±0.0875, while which were 0.173 to 0.890 with a mean of 0.401±0.207 (p<0.001) in 27 CML cases. Furthermore, Among these 27 CML cases, the gray ratio of Ku70 versus TBP in 12 CML cases in accelerating of acute phase was significantly higher than that in 15 CML patients in chronic phase with a mean value of 0.565±0.2159 vs. 0.269±0.0381 (p<0.001). These results indicated that the activity NHEJ in CML cells was approximately 2-fold higher than that in normal controls. Ku70, as the key protein of NHEJ, was expressed significantly higher in CML than that in normal BM cells. Moreover, as the CML progressed from chronic phase to accelerating or acute phase in company with a remarkable increase of Ku70 expression, more clones with variety of chromosome abnormalities other than the typical t (9;22) translocation emerged, suggesting an error-prone repair activity of the increased NHEJ in CML. The overactive DNA repair ability of NHEJ associated Ku70 proteins found in CML cells may highly correlated to the chromosome aberration in CML, especially to the genome instability during the disease progression.
High Antileukemic Efficacy and Shortened Neutropenia of Dose-Dense Induction (Sequential-HAM Followed by Pegfilgrastim) in Primary Acute Myeloid Leukemia - Results of a Pilot Study of the German AML-CG.
Authors: Braess Jan , Spiekermann Karsten , Buske Christian , Staib Peter , Ludwig Wolf-Dieter , Gruneisen Andreas , Sauerland Christa , Unterhalt Michael , Fiegl Michael , Wormann Bernhard , Kern Wolfgang , Heinicke Achim , Berdel Wolfgang , Büchner Thomas , Hiddemann Wolfgang 
Published: October 2019

Abstract
Dose density during early induction has been demonstrated to be one of the prime determinants for antileukemic efficacy. The German AML-CG therefore pilots a dose dense induction regimen S-HAM (sequential HD-AraC [3g/m2/12h d1,2,8,9] and Mitoxantrone 10mg/m2 [d3,4,10,11] followed by pegfilgrastim) in which two induction cycles are applied over 11 – 12 days as compared to conventional double induction, in which two cycles are applied over 25 – 29 days - thereby increasing dose density ca. two-fold in the critical first weeks of treatment. In the past 2,5 years 168 patients with de-novo AML (excluding APL) have been recruited into the trial with a median age of 53 years (range 18 – 78). Of 136 patients evaluable for response the following results were achieved: CR 62%, CRi 22%, PL 7%, ED 9% - resulting in an overall response rate (ORR) of 84%. The early death rate (ED) of 9% and the toxicity profile compared favourably with a historical control group of the AML-CG 1999 study (de-novo AML, < 60 years, HAM-HAM double induction) which demonstrated an ED rate of 14% (ORR 68%, persistent leukemia (PL) 18%). The high antileukemic efficacy of S-HAM was also demonstrated by the fact that 89% of patients had a blast count of < 10% one week after therapy as compared to less than 48% of patients of the HAM-HAM double induction group. Whereas even for patients with unfavourable cytogenetics (including complex aberrations) a median overall survival of 13,5 months was reached (23% at 2 years), for patients with favourable karyotypes overall survival at 2 years was 81%and for patients with intermediate karyotypes 74% after S-HAM treatment. Importantly the compression of the two induction cycles into the first 11 – 12 days of treatment seems actually beneficial for normal hematopoesis as demonstrated by a significantly shortened duration of critical neutropenia of 30 days as compared to 45 days after conventionally timed double induction. This shortening of critical neutropenia by more than 2 weeks was highly relevant for the duration of hospital stay and hospital costs. In conclusion S-HAM with pegfilgrastim support is a highly effective regimen in primary de-novo AML with a very favourable safety profile and significantly shortened duration of neutropenia. This regimen will therefore constitute the (dose-dense) experimental arm for a randomized comparison with standard double induction in the next generation of the German AML-CG studies.
Long-Term Prognostic Impact of the Use of Erythropoiesis-Stimulating Agents (ESA) in Patients (pts) with Chronic Myeloid Leukemia (CML) Treated with Imatinib.
Authors: Alvarado Yesid , Kantarjian Hagop , Verma Dushyant , Mattiuzzi Gloria , Aribi Ahmed , Ravandi Farhad , Borthakur Gautam , Cortes Jorge 
Published: October 2019

Abstract
Background: ESA have been reported to effectively improve the hemoglobin (Hb) in pts with CML who develop anemia during the course of therapy with imatinib and other tyrosine kinase inhibitors. Recently, it has been suggested that when ESA were administered to target a Hb ≥12 g/dL, they may promote tumor growth and decreased survival among pts with advanced head and neck cancer receiving radiation therapy, pts with non-small cell lung cancer, and pts with metastatic breast cancer receiving chemotherapy. We thus investigated whether pts with CML who had received ESA during the course of therapy with imatinib had an inferior long-term outcome.
Methods: We analyzed the outcome of 565 pts with CML in chronic phase treated with imatinib in our institution (306 previously untreated, 259 post imatinib failure).
Results: Based on the Common Terminology Criteria for Adverse Events (CTCAE) V. 3.0 of the National Cancer Institute (NCI), grade 1 anemia occurred in 235 (42%) pts, grade 2 in 180 (32%), grade 3 in 47 (8%), and grade 4 in 12 (2%) pts. A total of 245 (43%) pts received ESA at some point during the course of therapy. The median nadir Hb among pts treated with ESA was 9.4 g/dL [45 (18%) with grade 3–4 anemia] vs 11.2 g/dL [14 (4%) with grade 3–4 anemia] in those not treated with ESA. Treated patients received therapy with variable intermittent doses during a median time of 14 months (mo) range (1–96 mo). The observed increase in Hb with ESA therapy was >3 g/dL in 132 (54%) pts, 2–3 g/dL in 64 (26%), 1-<2 g/dL in 35 (14%), and <1 g/dL in 14 (6%) pts. The median Hb level achieved with ESA was 12.6 g/dL. The table summarizes the 5-year overall survival and event free survival (EFS) among pts treated with ESA and those not treated with ESA: As previously reported (Cortes et al. Cancer2004; 100:2396–402), the presence of anemia itself has a significant adverse effect on outcome in this patient population. The 5-year EFS for pts with anemia grade 3–4 was 56% vs. 79% for those with grade 0–2 (p=0.002). Corresponding figures for 5-yr OS were 82% and 88% (p=0.006).
Conclusion: There is no evidence that the use of ESA to manage anemia associated with imatinib therapy in pts with CML in chronic phase adversely affects long term overall survival or event-free survival.
INF- failure (%) Frontline Imatinib (%) OS: overall survival, EFS: event free survival (event = loss of complete hematologic response, loss of major cytogenetic response, transformation to accelerated or blast phase or death from any cause), INF: interferon, ESA: erythropoiesis-stimulating agents. ESA use OS EFS OS EFS No 84 75 92 84 Yes 82 68 89 85 P Value 0.59 0.12 0.58 0.68