bluuebunny/crossref_metadata_2025_split huggingface dataset:
Notch Activation Converts B Cells into a T Cell Fate at the Earliest Stages of B Cell Committed Progenitors.
Authors: Taneera Jalal , Smith Emma , Sigvardsson Mikael , Hansson Emil , Lindahl Urban , Martensson Inga-Lill , Jacobsen Sten Eirik 
Published: October 2019

Abstract
Notch activation has been suggested to promote T cell development at the expense of B cell commitment at the level of a common lymphoid progenitor prior to B cell commitment. Here, we explored the possibility that Notch activation might be able to switch the fate of already committed B cell progenitors towards T cell development upon Notch activation. To address this we overexpressed constitutively activated Notch-3 (N3IC) in B cell progenitors purified from transgenic mice in which human CD25 is expressed under control of the λ5 promoter. Strikingly, whereas untransduced and control transduced B220+λ5+CD3− B cell progenitors gave rise exclusively to B cells, CD4+ and CD8+ T cells but no B cells were derived from N3IC-transduced cells when transplanted into sublethally irradiated NOD-SCID mice. Gene expression profiling demonstrated that untransduced B220+ λ5+CD3− B cell progenitors expressed λ5 and CD19 but not the T cell specific genes GATA-3, lck and pTα, whereas CD3+ T cells derived from N3IC-transduced B220+λ5+CD3−cells failed to express λ5 and CD19, but were positive for GATA-3, lck and pTα expression as well as a and b T cell rearrangement. Furthermore, DJ rearrangements were detected at very low levels in CD3+ cells isolated from normal non-transduced BM, but were more abundant in the N3IC-transduced CD3+ BM cells. Noteworthy, N3IC-transduced B220+λ5+CD3−CD19+ proB cell progenitors failed to generate B as well as T cells, whereas N3IC-transduced B220+λ5+CD3−CD19− pre-proB cells produced exclusively T cells, even when evaluated at low cell numbers. In conclusion Notch activation can switch committed B cell progenitors from a B cell to a T cell fate, but this plasticity is lost at the Pro-B cell stage, upon upregulation of CD19 expression.
The Clinical Impact of Mild Hemophilia A, Report of a Cohort Study.
Authors: Scully Mary-Frances , MacGregor David , Walsh Meghan , Barrett Brendan , Kawaja Marc , Sheppard Charlotte 
Published: October 2019

Abstract
Due to a founder affect certain regions of the Canadian province of Newfoundland and Labrador have a very high prevalence of mild Hemophilia A. To accurately plan for future health related needs of these patients, a base-line cross-sectional study of a large cohort segregating a known founder mutation (Val2016Ala) was undertaken.
Characteristics of Study Participants Characteristic Affected Males Control Males P-Values (Affected vs Control) Carrier Females Control Females P-Value (Carrier vs Control) Values are expressed as number, mean*, median(interquartile range)†, or percentage Overall N 61(5–76yrs) 44(4–81yrs) 0.883 88(8–88yrs) 65(16–78yrs) 0.935 Factor VIII* 0.15(0.05) 1.29(0.37) <0.001 0.78(0.31) 1.34(0.41) <0.001 Hepatitis Bc Antibodies 15.8%(9/57) 0%(0/28) 0.012 0%(0/75) 0%(0/58) - Hepatitis C Positive 19.7%(12/61) 0%(0/33) 0.001 0%(0/88) 0%(0/65) - HIV Positive 1.6%(1/61) 0%(0/33) 0.420 0%(0/88) 0%(0/65) - Diabetes 24.4%(11/45) 6.1%(2/33) 0.031 - - - BMI†(Adults Only) 30.0(27.0–33.0) 27.0(26.0–30.0) 0.028 29.0(20–57) 28.0(19–46) .446 Statistically Significant Difference SF-36 & Colorado PE-05 Mean Scores for Affected and Unaffected Males Affected Males Affected Males Affected Males Unaffected Siblings Unaffected Siblings Unaffected Siblings t-test Difference vs References Dimension n Mean SD n Mean SD P-Value P<0.05)* Affected Males(age 23–76 years) Unaffected Siblings(age 20–81 years) SF-36 Scores General Health Scale 44 58.1 28.7 32 71.4 21.4 0.024* Role Emotional 44 89.2 19.9 33 98.0 5.5 0.007* Colorado PE-05 Musculoskeletal Scores Axial Deformity 47 0.9 1.4 33 0.2 0.8 0.008* Range of Motion 47 4.2 2.0 33 2.9 1.8 0.005* Gait 47 2.4 3.5 33 0.4 1.4 0.002* Left Ankle 47 3.3 5.0 33 1.0 2.9 0.015* Right Ankle 47 3.2 4.6 33 0.7 1.3 0.002*
There was a positive association between the SF-36 General Health Scale scores and the following values of the Colorado PE-05 Scores. Gait (R -.45, p<.001), Range of Motion (R-.08, P=.508), Axial Deformity (R -.35, P<.001), Right Ankle (R -.42, p<.001), and Left Ankle (R-.49, p<.001). The association between the SF-36 Role Emotional Scales for affected males and the values of the Colorado PE-05 was also positive. Gait (R -.52, P<.001), Range of Motion (R - .30, P = .01), Axial Deformity (R -.54, P<.001), Right Ankle (R -.06, P<.001) and Left Ankle (R-.52, p<.001). No patients studied have acquired an inhibitor to Factor VIII. Obese males (BMI >30) had significantly greater impairment in their Range of Motion than non-obese males (4.59 vs (3.34), p<0.05) independent of whether or not they had hemophilia. These results are consistent with our clinical experience that mild Hemophilia A causes episodic bleeding, lack of recognition and delayed treatment leads to significant morbidity. The association with diabetes was unexpected. Future interventions will now focus on prevention and early treatment of ankle bleeds and will include strategies to reduce the risk of obesity.
A Prospective, Observational Study of the Effectiveness and Safety of a Weekly Fixed Dose of Darbepoetin alfa with Current Practice Iron Management for the Treatment of Chemotherapy-Induced Anemia (CIA): A Subanalysis in Patients (pts) with Lymphoproliferative Malignancies (LPM).
Authors: Alegre A. , Salar A. , Roig I. , Bermejo J.C. , Palacios A. , de Paz R. , Arranz R. , Fernández A. , Calzada R. , Iturralde P. ,   On Behalf of the AMG-DAR-2002-01 Study Group
Published: October 2019

Abstract
Background: Darbepoetin alfa (Aranesp®) is a unique erythropoiesis-stimulating protein effective for the treatment of CIA when administered weekly (QW), every 2 weeks (wks) or every 3 wks. Fixed dosing of darbepoetin alfa is routinely used in clinical practice, but little data are available on its patterns of use and the impact of iron status on its effectiveness.
Methods: This was a subanalysis of LPM pts included in a prospective, single-arm, multicenter study conducted in Spain. Pts were ≥ 18 yrs old, anemic (hemoglobin [Hb] ≤11 g/dL), scheduled to receive ≥ 12 wks of chemotherapy, and without iron, vitamin B12, or folate deficiencies. Pts were treated with darbepoetin alfa 150 mcg QW; the dose was to be doubled to 300 mcg QW if Hb increased <1 g/dL after 4 wks. Oral iron (200 mg QD) was recommended if transferrin saturation was ≤ 30%, transferrin was ≥ 400 mcg/dL, and/or ferritin was ≤ 300 mcg/L at any time during the study. The primary endpoint was hematopoietic response (Hb increase ≥ 2 g/dL or Hb ≥ 12g/dL in the absence of transfusions in the previous 28 days). Secondary endpoints included the percentage of pts with functional or absolute iron deficiency and its correlation with response rates, change in FACT-Fatigue score from baseline to end of treatment (EOT), and safety.
Results: Of a total of 293 patients enrolled, 129 had LPM and were included in this analysis. Of the LPM patients, 55% were women, median age was 67.3 yrs (range: 20.6–88.4), median weight was 67 kg (range: 40.5–115.0). Eleven percent had Hodgkin’s disease, 33.9% had non-Hodgkin’s lymphoma. 5.5% had chronic lymphocytic leukemia, and 49.6% had multiple myeloma. Most pts (80.5%) had baseline Hb between 9–11 g/dL; 19.5 % had Hb < 9 g/dL. Darbepoetin alfa was administered for a median of 16 wks (range:1–16). At wk 5, 25.6 % of pts had their dose doubled to 300 mcg QW. The observed hematopoietic response was 70.73% (95%CI: 62.69, 78.77). The proportion of pts transfused from wk 5 to EOT was 12.7%. During the study, 31.5% pts received oral iron, 10.3% developed absolute iron deficiency, and 8% had iron blockade. Mean (95% CI) FACT-Fatigue score increased from 34.1 (32.2, 35.9) to 40.0 (38.2, 41.8) (p<0.0001). Darbepoetin alfa was well tolerated with 2.4% of pts experiencing adverse events considered related to the study drug.
Conclusions: darbepoetin alfa, given as a fixed dose, is an effective and well-tolerated treatment for CIA in pts with LPM. Darbepoetin alfa significantly improved health-related quality of life in this routine clinical practice setting.
Erythropoietin Response to Anemia Is Impaired in Patients with Hematologic Malignancies.
Authors: Shen Ti , Shi Yuankai , Zhu Jun , Han Bing 
Published: October 2019

Abstract
Anemia is a common complication in patients with hematologic malignancies, either before or after chemotherapy. To find out whether anemic patients with hematologic malignancies have a lower erythropoietin (Epo) response, we analyzed serum Epo levels in these patients. Serum samples for measurement of Epo levels were obtained from 80 patients from three medical centers. Patients had multiple myeloma (MM, n=26), chronic lymphocytic leukemia (CLL, n=6) or non-Hodgkin’s lymphoma (NHL, n=48). Thirty patients had anemia (mean hemoglobin [Hb] level 8.4±1.6 g/dl) and 50 patients were not classed as anemic, with mean Hb levels of 12.7±1.4 g/dl. To provide control values, serum Epo levels were also determined in patients with iron-deficiency anemia (IDA; n=20) and in healthy individuals (n=20). Serum Epo levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients with severe liver or renal dysfunction, low platelet counts or blood loss were excluded. The complete blood cell count (CBC), reticulocyte count, serum lactate dehydrogenase (LDH), liver and renal function, serum iron (SI), total iron-binding capacity (TIBC), transferrin saturation (TSAT), and serum ferritin (SF) levels were evaluated concomitantly. There were no significant differences in CBC, LDH, liver and renal function, SI, TIBC, TSAT and SF values between malignant patients with or without anemia (P>0.05). In patients with hematologic malignancy, those with anemia had higher Epo levels (mean 97.8±183.9 mIU/ml) than those without anaemia (mean 27.8±85.4 mIU/ml; P<0.001). In patients with IDA, the Epo response was inversely correlated with Hb level (r= −0.5, P<0.05), whereas the expected inverse linear relationship between serum levels of Epo and Hb was absent in the group with hematologic malignancies (r= −0.14). Anemic patients with malignancy, and IDA patients both had elevated Epo levels compared with normal controls (means, 97.8±183.9 mIU/ml, 158.3±308.6 mIU/ml and 9.2±4.0 mIU/ml, respectively; both P<0.001 vs controls). However, after correcting for Hb level, anemic patients with malignancy were found to have significantly lower Epo levels than patients with IDA (P=0.032) indicating a decreased Epo response in the former group. These findings indicate that anemia associated with hematologic malignancy may result from an inappropriately low Epo response. Epo treatment should benefit this group of patients.
The Role of Lactadherin in the Phagocytosis of Phosphatidylserine-Expressing Sickle Red Blood Cell by Macrophages.
Authors: Dasgupta Swapan K. , Thiagarajan Perumal 
Published: October 2019

Abstract
Sickle cell anemia, the most common serious hemoglobinopathy, is associated with a markedly reduced life span of red blood cells due to their preferential clearance by macrophages. During polymerization of sickle hemoglobin, phosphatidylserine, an anionic phospholipid normally present exclusively on the inner leaflet of the membrane bilayer is exteriorized to outer leaflet. This exposure of phosphatidylserine is thought to be a tag for macrophage recognition. Lactadherin, also known as milk fat globule-EGF factor 8, is a phosphatidylserine-binding glycoprotein secreted by macrophages that promotes the engulfment of apoptotic cells. Here, we investigated the role of lactadherin in the phagocytosis of sickle red blood cells.
The binding of fluorescein-lactadherin to normal and sickle red blood cells was studied by flow cytometry. We quantified the effect of lactadherin on phagocytosis of red blood cells by monocyte-derived macrophage.
In normal individuals, less than 0.5% of red blood cells showed any binding to lactadherin when analyzed by flow cytometry. However, in sickle cell patients, circulating red blood cells showed 2 to 10- fold increase in lactadherin binding (P<0.0002). Lactadherin stimulated the phagocytosis of resting sickle red blood cells by macrophages but had no significant effect on the phagocytosis of normal red blood cells. Deoxygenation of sickle red blood cells further increased the lactadherin binding and phagocytosis. Antibodies to integrin αVβ3 also inhibited macrophage binding and phagocytosis.
These results show lactadherin may play a major role in sickle red cell clearance by anchoring the phosphatidylserine-expressing sickle red blood cells to integrins on tissue macrophages.
Equivalence of Liquid and Freeze-Dried Formulations of WinRho® SDF.
Authors: Sinclair Christopher J. , Ruckle Jon , Swearingen Dennis , Kisicki James C. , Marbury Thomas C. , Genereux Maurice , Brooks William 
Published: October 2019

Abstract
WinRho® SDF is licensed in the USA, Canada and Europe to treat ITP and prevent Rh isoimmunization. Although safe, efficacious and cost-effective, WinRho® SDF has only been available in a freeze-dried formulation. In order to simplify injection preparation and reduce the possibility of preparation errors, a liquid formulation of WinRho® SDF has been developed. The pharmacokinetics and tolerability of the liquid and freeze-dried preparations were compared in 2 randomized, double-blind, multi-center phase 1 studies that were conducted in healthy adult volunteers. Subjects were administered one of the formulations either IM (300 μg or 15 μg/kg) or IV (50 μg/kg). Pharmacokinetics (AUC, Cmax, t1/2, tmax) and safety data (adverse events and laboratory assessments) were assessed over 84 days. In total, 142 subjects received either the liquid or freeze-dried formulations (N=71 each group). Following IV or IM administration, the ratios (90% confidence intervals) for AUC and Cmax were within the FDA required acceptance range of 80–125% to demonstrate bioequivalence. Both formulations had comparable half-lifes of ~18–19 days and ~26 days following IV or IM administration, respectively. While tmax occurred immediately following IV administration, tmax was ~3–7 days after IM administration. Both formulations were similarly tolerated following either IV or IM administration. The most common adverse events were headaches and neck/back pain. Liquid WinRho® SDF was demonstrated to be bioequivalent to the freeze-dried formulation following IV or IM administration. This suggests that liquid WinRho® SDF may be therapeutically equivalent to the freeze-dried formulation and provide a more convenient presentation for use.
The Predictive Value of D-Dimers on the Occurrence of Thromboembolic Events and Death: A Prospective Multicentric Study.
Authors: Mahe Isabelle , Drouet Ludovic , Chassany Olivier , Sollier Claire Bal dit , Mazoyer Elizabeth , Minh-Muzeaux Sophie , Caulin Charles , Bergmann Jean-François 
Published: October 2019

Abstract
Background: Atrial fibrillation (AF) is the most common arrhythmia, especially in elderly subjects (more than 10% of those older than 80). The main complication is the occurrence of ischemic stroke. Oral anticoagulants reduce by 2/3 the thromboembolic risk but increase the risk of bleeding. The question for the clinician is to identify patients at highest thromboembolic risk who would the most benefit from anticoagulant therapy: in this way, the dosage of D-dimer, a marker of activation of coagulation may be of interest.
Primary aim: To assess the predictive value of D-dimer levels on the occurrence of thromboembolic event or death.
Methods: Patients with AF were included whatever the treatment they received, when they were in a stable clinical condition and when the antithrombotic treatment remained unchanged during the last month. It is a prospective multicentric study performed in 25 departments of AP-HP. Patients had visits and biologic dosages including D-dimer every 4 months. At every visit, patients were questioned about ischemic events (stroke, transient attack, systemic embolism, myocardial infarction), venous thromboembolic events, the occurrence of disease and bleeding events since the last visit. D-dimer dosage was centralised in the Laboratory of Pr Drouet (Lariboisière hospital). The usual management of the patient was in charge of the practitioner and not modified by the study. The planned duration of follow-up was 1 year to 2 years.
Results: 434 patients were included (mean age 80 years) from 02/01/01 to 04/06/30. Antithrombotic treatments at inclusion were: oral anticoagulant (n=240), antiplatelet agents (n=57), no antithrombotic therapy (n=45). Follow-up has ended on 05/06/30.
Discussion: Clinical events have been recorded. D-dimer measurements are ongoing. Results will be provided at the meeting (including D-dimer levels and clinical events).
The Outcome of Pregnancy in Patients with Thrombophilia after Anticoagulation.
Authors: Jiang Qingqi , Andersen Judith 
Published: October 2019

Abstract
Background: Both inherited and acquired thrombophilia predispose pregnant women to venous thromboembolism and recurrent fetal loss. The safety profile and tolerability of low molecular heparin (LWMH) has allowed us to evaluate effects of anticoagulation in the outcome of pregnancy in patients with thrombophilia.
Methods: 20 patients with thrombophilia received either tinzaparin or enoxaparin combined with aspirin before and during pregnancy and the outcome of pregnancy was monitored for a period of 2 years. The median age of the patients was 28 years (25–49); 75% were Caucasians, 20% were aferican-american, 5% were others. The inherited and acquired thrombophilias include Factor V leiden mutation, prothrombin mutation in G20210A, mutation in methylenetetrahydrofolate (MTHFR), protein S deficiency, protein C deficiency, hyperhomocyteinemia, antiphospholipid syndrome, sticky platelet syndrome, etc. The majority of patients had more than 2 thrombophilia factors and had history of miscarriage. 15 of 20 patients (75%) received tinzaparin and 4 of 20 (20%) patients received enxoparin subcutaneously before they were conceived. Only one patient received unfractionated heparin. The LWMH was continued during pregnancy until 34 to 36 weeks gestation when it was changed to unfractionated heparin in order to prevent large amount of bleeding from upcoming delivery. All of the patients also received aspirin prior, during, and after the pregnancy. There were 21 live births including one triplet and one twins. Only two patients were complicated with miscarriage. There was no episode of severe bleeding or thromboembolism during pregnancy or postpartum.
Conclusion: LWMH and aspirin has been effective in the prevention of fetal loss in women with thrombophilia disorders.
Molecular Typing for Kidd Blood Group in Taiwan.
Authors: Tzeng Cheng-Hwai , Lyou Jau-Yi , Chen Pei-Shan , Liu Hsueng-Mei , Chen Ying-Ju , Liu Jin-Hwang 
Published: October 2019

Abstract
Background:The Kidd (JK) blood group system is clinically important intransfusion medicine. Alloantibodies to antigens in this system may be produced following blood transfusion or during pregnancy and can result in serious hemolytic transfusion reactions and hemolytic disease of the newborn (HDN). The two major codominant alleles of the JK gene, Jka and Jkb, have a similar frequency in Caucasian populations (0.51 and 0.49, respectively) and define 3 common phenotypes Jk(a+b+), Jk(a+b-), Jk(a-b+), while frequency of Jk(a-b-) or Jknull phenotype is exceedingly rare. Many individuals of Polynesian extraction have been identified as Jknull. Its frequency and molecular characterization for Chinese people in Taiwan, however, has not yet been clarified.
Study design and methods: By using the lately developed single-tube allele-specific primer/multiplex PCR technique, a total of 320 random whole blood samples were analyzed. In addition, three samples already serologically proven as Jknull phenotype in our Lab were also investigated.
Results: None of the 320 random whole blood samples was serologically typed as Jk(a-b-), while the frequencies of three other phenotypes were 47.5% for Jk(a+b+), 23.1% for Jk(a+b-), and 29.4% for Jk(a-b+). Interestingly, two Jka/Jk and four Jkb/Jk were identified, resulting in a gene frequency of Jka - 46.72%, Jkb - 52.34% and silent Jk - 0.94%. As for the three samples of Jknull phenotype all belonged to the so-called Polynesian type, i.e.3′-acceptor splice site G->A mutation of intron 5 that resulted in the skipping of exon 6 (called mutation JKΔ6).
Conclusion: The present study confirms that the single-tube allele-specific primer/multiplex PCR technique has enabled genomic typing of the Kidd blood group easier and reliable. The frequency and molecular characterization of JK phenotypes for Chinese people in Taiwan have been clearly characterized.
A Comparison of Administration Time between Red Blood Cell Transfusion and Chemotherapy.
Authors: Chin-Yee Ian H. , Xenocostas Anargyros , Cheung Wendy W. , Hibbert Anita S. 
Published: October 2019

Abstract
In oncology patients, the majority of chemotherapy and red blood cell (RBC) transfusions occur in outpatient ‘chemotherapy’ units, where they compete for resources such as nursing time and “chair-time”. This study was to accurately assess the “chair-time” consumed by transfusion patients, in order to estimate the chemotherapy administration opportunities lost to RBC transfusions. Over four weeks, “chair-time”, defined as the time difference between the admission of each patient into care to their time of discharge, was prospectively evaluated in a tertiary-care outpatient cancer clinic with a referral population base of 2 million. Chair-times were then grouped into three types of care - RBC transfusions, chemotherapy administrations, and “other” (phlebotomy, central line catheter care, etc.) - to enable comparison. Chair-time is reported as a mean (+/− SD). Patient demographics (age, sex, diagnosis, chemotherapy regimen, pre-transfusion hemoglobin) were also recorded. A total of 1354 visits to the chemotherapy suite were captured over one month. Of these, 1279 visits had evaluable data for further analysis, and can be divided as follows: 1023 (80%) chemotherapy administrations, 44 (3.4%) RBC transfusions, and 212 (16.6%) “other”. 38 patients accounted for the 44 RBC transfusions. Of those, 14 were hematological malignancy patients (ALL, AML, CLL, HD, Myeloma, Lymphoma), 12 were solid tumor patients and the remaining 12 had other hematological disorders (Aplastic Anaemia, Myelodysplasia, Myelofibrosis). Among the malignant patients, 20 were receiving chemotherapy during the study period. The mean chair-time for all accurately recorded events was 1 hr 49 min (+/− 1 hr 39 min). Divided into types of care, the mean chair times were: 1 hr 59 min (+/− 1 hr 40 min) for chemotherapy, 3 hr 51 min (+/− 47 min) for RBC transfusion, and 34 min (+/− 43 min) for “other” care. The average time per RBC unit transfused was 1 hr 49 min (+/− 19 min) and the average number of units per transfusion was 2.2 units. When chemotherapy chair-times were examined, and patients were grouped by diagnoses, it was found that patients with lymphoma (most commonly treated with R-CHOP, or other Rituximab containing regimens), and gynecological cancers (most commonly treated with regimens containing carboplatin) had the longest chair-times, at 4 hr 20 min (+/− 1 hr 24 min) and 3 hr 50 min (+/− 2 hr 11 min) respectively. Although RBC transfusions make up only 3.4% of all events in our chemotherapy suite, they occupy almost twice as much chair-time as compared to chemotherapy. Depending on the patient population, clinics with a high rate of RBC transfusions might consider transfusion alternatives, as emerging monoclonal antibody chemotherapies augment the time necessary for administering chemotherapy, and chair-time becomes an increasingly valuable resource.