bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between C-Reactive Protein in the First 1-3 Days Post-Transplant and Allogeneic Immune Reactions in Pediatric Haploidentical Stem Cell Transplantation
Authors: Chen Yao , Liu Kai-Yan , Huang Xiao-Jun , Huan Chen , Wang Feng-Rong , Wang Jing-Zhi , Zhang Xiao-Hui , Chen Yu-Hong , Wang Yu , Han Wei , Chen-Hua Yan , Zhang Yuan-Yuan , Xu Lan-Ping 
Published: October 2019

Abstract
Background: C-reactive protein (CRP) has been shown to be a reliable biomarker of innate immunity. The purpose of the current study was to evaluate whether CRP levels in the first 1-3 days could predict allogeneic immune reactions including engraftment syndrome (ES) or acute graft-versus-host disease (GVHD) under haploidentical stem cell transplantation (SCT) in children.
Patients and methods: The study population comprised 175 consecutive pediatric patients (age no more than 18 years) who received haploidentical SCT from Oct, 2009 to Dec, 2014. All the children followed Beijing protocol in our institute as previously described. Allogeneic immune reactions include engraftment syndrome and acute GVHD. ROC analysis was performed to identify cutoff CRP value in the first 1-3 days post-transplant that best identified patients with allogeneic immune reactions. Patients were classified into 2 groups as high-CRP group (≥cut-off value) and low-CRP group (<cut off value).
Results:Totally, 129 patients (73.7%) were alive and without primary disease.The median age of recipients was 14 years (range: 2-18 years). The primary diseases were as follows: ALL in 95 (54.3%), AML in 62 (35.4%), hybrid acute leukemia in 3 (1.7%), CML in 10 (5.7%), and MDS in 5 (2.9%). Of the 175 patients, 68 (38.9%) developed ES on a median of day 10 (range: 7-16). 51(29.1%) out of 175 children developed 2-4 grade acute GVHD on a median of day 30 (range: 22-89) including 15 (8.6%) patients of severe acute GVHD on a median of day 29 (range: 22-85). Higher incidence of ES, 2-4 grade GVHD and 3-4 grade GVHD were totally observed in high-CRP group, compared to the low-CRP. A multivariate analysis demonstrated that high-level CRP(≥20.1 mg/L)in day 1-3 post-transplant was a risk factor for the development of allogeneic immune reactions. High CRP group was associated with an increased occurrence of ES (HR=2.046; 95%CI=1.204-3.477; P=0.008), II-IV aGVHD (HR=2.203; 95%CI=1.192-4.073; P=0.001) and severe GVHD (HR=6.371; 95%CI=1.798-22.581; P=0.004).
Conclusions: Our data suggested higher CRP level during the first 1-3 days post-transplant could be a predictor of allogeneic immune reactions in pediatric haploidentical SCT.

Disclosures
No relevant conflicts of interest to declare.
High-Efficiency Transduction of Primary Human Hematopoietic Stem/Progenitor Cells By AAV6 Vectors: strategies for Overcoming Donor-Variation and Implications in Genome Editing
Authors: Ling Chen , Bhukhai Kanit , Yin Zifei , Tan Mengqun , Yoder Mervin , Leboulch Philippe , Payen Emmanuel , Srivastava Arun 
Published: October 2019

Abstract
We have reported that of the 10 commonly used AAV serotype vectors, AAV6 is the most efficient in transducing primary human hematopoietic stem/progenitor cells (HSPCs). However, the transduction efficiency of the wild-type (WT) AAV6 vector varies greatly in HSPCs from different donors. Here we report two distinct strategies to further increase the transduction efficiency in HSPCs from donors that are transduced poorly with the WT AAV6 vectors. The first strategy involved modification of the viral capsid proteins where specific surface-exposed tyrosine (Y) and threonine (T) residues were mutagenized to generate a triple-mutant (Y705+Y731F+T492V) AAV6 vector. The second strategy involved the use of ex vivo transduction at high cell density, which revealed a novel mechanism, which we have termed, 'cross-transduction'. The combined use of these strategies resulted in transduction efficiency exceeding ~90% in HSPCs. Our studies have significant implications in the optimal use of capsid-optimized AAV6 vectors in genome editing in HSPCs.

Disclosures
Leboulch: bluebird bio: Patents & Royalties. Payen:bluebird bio: Patents & Royalties. Srivastava:AGTC; Genzyme: Patents & Royalties.
Hemophilia Lend-Lease Program in Italy Successfully Meets Albania Factor Needs
Authors: Aledort Louis M. , De Luca Michele , Jose Caldes Pinilla Maria , Zanobini Alberto , Carli Simona , Godo Anila , Manastirliu Ogerta , Kolaj Gentian , Caja Tatiana , Neziri Vera 
Published: October 2019

Abstract
Many countries can not provide yet an adequate haemophilia care for their patients. Albania is among the countries that are trying now to improve its healthcare system but still do not have fully implemented it. As to the Haemophilia treatment the need of FVIII for patients exceeds the available resources thus jeopardizing the possibilities of having I place prophilaxis and/or major chirurgic treatments.
Tuscany is one of the region in Italy where the rate of Albanian inhabitant people is higher. Among them many are also blood donors and the links between Italians and the Albanian community are quite strong as well as the Tuscany commitment toward Albania in the general health system (many are the programs put in place by the International Health Cooperation of Tuscany).
In this context in 2013 a joint program between Hospital Mother Teresa in Tirana and Hospital Meyer in Florence was undersigned for the supply of 3 MIU of FVIII at 9 cents/I.U. from donors of the region each year for three years.
Albania recognizes that hemophilia treatment is a urgent part of their healthcare plan and expects to be able soon to provide more funds to continue this program. Albania has been offered more FVIII from Italian donors for at least a 5 years period in the framework of an Italian recent law that is encouraging the use of FVIII in excess to Italian needs for other countries and with the support of Kedrion , who Is the company fractionating the plasma from Tuscany donors into finished product. Kedrion not only committed to pay for the shipping of goods from Italy to Albania but it is also acting as a partner and liaison between Tuscany and the country
Industry should take note that with local philanthropy and financial support from the biologic industry one can achieve both improving healthcare and not just donating product but working with developing countries to make them support their population.

Disclosures
Aledort: Kedrion: Other: chair scientific advisory committee for kedrion.
Runx1 Deficiency and MDS-Associated U2af1 Mutation Cooperate for Leukemia Development in a New Mouse Model
Authors: Zhen Tao , Liang Fei Dennis , Zhao Ling , Lopez Guadalupe , Varmus Harold , Liu Pu Paul 
Published: October 2019

Abstract
The pathogenesis of hematopoietic malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), is very complicated with mutiple genetic alterations required for full-blown disease. Mutations of splicing factor genes, including U2AF1, are found in overal half of MDS patients and 5~10% de novo AML patients. U2AF1 mutations, occuring in roughly 10% of patients with MDS and 3% in de novo AML, are heterozygous and localized almost exclusively in two codons, S34 and Q157, suggesting they are gain-of-function mutations. In addition, our recent studies suggest retention of the wild type U2AF1 allele is required for cell viability (Fei et al., BioRxiv, 2016). Interestingly, RUNX1 is the most commonly co-mutated gene in MDS patients with U2AF1 mutations, and U2AF1 and RUNX1 are also co-mutated in some AML patients. These findings suggest RUNX1 deficiency and U2AF1 mutation cooperate in the pathogenesis of MDS and AML.
To test this hypothesis, we crossed Cre-based conditional Runx1 knockout mice (Runx1f/f) with mice carrying a newly developed Cre-based conditional U2af1-S34F mutation (U2af1+/S34F) to generate Runx1f/f, Mx1-Cre, U2af1+/S34Fmice, which express U2af1-S34F and deficient-Runx1 after inducing Cre from the Mx1 promoter with poly (I:C). We found that U2af1-S34F attenuated the Runx1-/--induced increase of myeloid cells in spleen and bone marrow, as well as the increase of progenitor (lineage-/Sca1-/C-kit+) and stem cells (lineage-/Sca1-/C-kit+). Competitive repopulation assays showed that combining the U2af1 mutation and Runx1 deficiency impaired the transplantation capacity of bone marrow progenitor cells, especially for the myeloid lineage. We further aged these mice to examine the cooperative effects of U2af1-S34F and Runx1 deficiency in disease progression, upon the treatment of a one time, low-dose N-ethyl-N-nitrosourea. Mx1-Cre, U2af1+/S34F mice didn't show survival defect when compared to control mice, while the Runx1f/f, Mx1-Cre mice developed MDS, as previously reported. Interestingly, of fourteen Runx1f/f, Mx1-Cre, U2af1+/S34F mice, two developed AML, and the rest developed MDS. Moreover, transplanted spleen and bone marrow cells from one of four MDS Runx1f/f, Mx1-Cre, U2af1+/S34F mice also developed AML in the recipients. Although Runx1f/f, Mx1-Cre mice also had MDS, their MDS cells did not develop into leukemia after transplantation. Our data therefore suggest that Runx1 deficiency and MDS-associated U2af1 mutation can cooperate in the genesis of AML from MDS.

Disclosures
No relevant conflicts of interest to declare.
Genomic Analysis of Plasma DNA in Prenatal Medicine and Beyond
Authors: Lo Yuk Ming Dennis 
Published: October 2019

Abstract
The discovery of cell-free fetal DNA in maternal plasma has enabled the development of noninvasive prenatal testing (NIPT). With the increased use of NIPT globally, there have been a number of reports of plasma DNA aberrations that have orignated from maternal malignancies, rather than signifying genomic aberrations in the fetus. In this regard, it would be highly desirable to develop a technology for tracing the tissue of origin of genomic aberrations observed in plasma. Hence, we have developed a technology called plasma DNA tissue mapping which allows this to be achieved. Through the development of over 5800 methylation markers, we are able to deduce the tissue of origin of plasma DNA molecules. We have demonstrated the utility of this approach by tracing genomic aberrations observed in the plasma of a pregnant woman during the course of NIPT to a B-cell lymphoma. We believe that this technology would be broad applications in medical research and diagnostics.

Disclosures
Lo: Cirina Limited: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Xcelom Limited: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Illumina: Patents & Royalties; Sequenom: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.
Platelet Toll-Like Receptors: Bridging Inflammation and Immunity
Authors: Kubes Paul 
Published: October 2019

Abstract
Since the discovery that there is a series of pattern recognition receptors that allow the immune system to detect pathogens, there has been a lot of work to elucidate the signaling molecules that contribute to this detection system. Although the cell types involved would seem to be just as important, our understanding of which cells are critical remains less well explored. Using intravital imaging to visualize the different cell types, we were surprised to find that in almost all conditions that we examined, platelets were rapidly recruited to afflicted tissues. Under some conditions, platelets bound vascular macrophage including Kupffer cells and helped contain bacteria. These were instantaneous responses. At later times, platelets bound neutrophils and induced the production of neutrophil extracellular traps (NETs) that helped to catch bacteria as well as viruses but did induce some local vascular injury. In some scenarios, platelets bound endothelial cells and whether this was to wall off and contain infections or a hijacking of platelets by bacteria to induce vascular dysfunction and poor perfusion remains unclear. Visualizing platelets in sterile injury also revealed important contributions to helping recruit other immune cells that help to heal. The role of the platelet as an effector in infections and inflammation will be discussed.

Disclosures
No relevant conflicts of interest to declare.
Observations on the Changes in the Kinetics of Red Cell Proliferation Following Irradiation and Hypertransfusion
Authors: STOHLMAN FREDERICK 
Published: October 2019

Abstract
Data are presented on the changing pattern of the Fe59 uptake and emergence curve following irradiation and hypertransfusion. The data obtained appear to be inconsistent with the notion that population pressure influences the release of red cells from the marrow. The implications of these data on the understanding of the kinetics of red cell production are discussed.
RENAL FUNCTION DURING CHRONIC ANEMIA IN MAN
Authors: BRADLEY STANLEY E. , BRADLEY GERALDINE P. 
Published: October 2019

Abstract
1. Renal function has been studied quantitatively in 15 patients with chronic anemia, 8 of whom were proved to have pernicious anemia. In 7 the anemia was secondary to chronic blood loss, iron deficiency, paroxysmal nocturnal hemoglobinuria, and leukemia. The effective renal plasma flow and glomerular filtration rate were measured by clearance technics; and tubular function, by saturation methods (diodrast Tm and glucose Tm).
2. The effective renal plasma flow, the glomerular filtration rate, and the filtration fraction (percentage of plasma filtered at the glomerulus) were reduced slightly below the normal values in most subjects. The effective renal whole blood flow was always greatly reduced, by 46 per cent on the average in males and by 31.8 per cent in females.
3. Since arterial pressure was not significantly depressed it was concluded that renal vasoconstriction occurs in chronic anemia, possibly as a homeostatic device for the diversion of blood to tissues more sensitive to oxygen lack. The relatively small reduction of filtration fraction implies afferent and efferent arteriolar vasoconstriction with dominance by the afferent arterioles. These changes were shown to be reversible, a return to normal values paralleling the return of the blood picture to normal.
4. Diodrast Tm was reduced significantly in 9 of 10 patients while the values of glucose Tm were normal in 6 of 7 patients. The normal values for glucose Tm indicated continued operation of all glomeruli and implied the absence of shunting or of cessation of blood flow in any significant portion of the kidney. The fall in diodrast Tm, which appeared to be reversible in 2 of 4 individuals, was interpreted as evidence of intracellular dysfunction rather than destruction or inactivation of nephrons.
MONOCYTIC LEUKEMIA A CASE REPORT ILLUSTRATING VARIATIONS IN THE CLINICAL PICTURE
Authors: RAPPOPORT ARTHUR E. , KUGEL VICTOR H. 
Published: October 2019

Abstract
Monocytic leukemia is an entity that has engendered a variety of divergent clinical and histologic opinions. A case is presented in which prolonged and intensive clinical and laboratory observations demonstrate the erratic course of this disease and illustrate the erroneous conclusions that may be derived from inconstant, momentary observations of this dynamic process. Study of the "natural history" of monocytic leukemia yields observations which tend to reconcile many of the hitherto conflicting opinions regarding this disease.
The origin and characteristics of the monocytic cell are discussed, and its probable derivation from mesenchyma is emphasized.
HEMATOLOGIC OBSERVATIONS IN A CASE OF KALA-AZAR
Authors: RACHMILEWITZ M. , BRAUN K. , DE VRIES A. 
Published: October 2019

Abstract
The hematologic findings in a case of kala-azar under the influence of specific treatment are described. The type of the anemia, the hyperplastic bone marrow, the increased urobilinogen output before treatment, and the subsequent changes following treatment strongly suggest increased red cell destruction (most probably by phagocytosis) as the cause of the anemia.
CONGENITAL HEMOLYTIC ICTERUS IN A NEGRO FAMILY
Authors: GOODMAN E. G. , CATES B. R. 
Published: October 2019

Abstract
1. A Negro family is reported in which 3 sisters were found to have congenital hemolytic icterus.
2. All members of the family observed showed strong Negroid characteristics. There was nothing to suggest an admixture of white blood.
3. The literature was reviewed. Including the 3 reported in this paper, 8 cases have been reported. The disease may be more common in the female as the reported cases show 7 females to 1 male.
4. Congenital hemolytic icterus, on rare occasions, occurs in the Negro race and recognizing it as such is helpful since splenectomy is of distinct value.
THE VALUE AND THE LIMITATIONS OF THE COAGULATION TIME IN THE STUDY OF THE HEMORRHAGIC DISEASES
Authors: QUICK ARMAND J. , C. RENE HONORATO , STEFANINI MARIO 
Published: October 2019

Abstract
The coagulation time is a measurement of the intrinsic power of the blood to convert fibrinogen to fibrin. It is an empirical test no matter how performed, and therefore in order to be reliable requires that the test be done on venous blood under strictly controlled conditions. A recommended procedure is outlined in detail.
The coagulation time is prolonged in hemophilia, hypoprothrombinemia, afibrinogenemia and heparinemia. In hemophilia, the coagulation time theoretically is a measure of the severity of the disease but practically is of limited value since the coagulation time may be within normal limits in some patients; the prothrombin consumed in the coagulation of hemophilic blood is therefore a better guide for diagnosis. The coagulation time in hypoprothrombinemia is relatively little prolonged until a drastic reduction occurs. The test is therefore of no value for establishing a hemorrhagic condition in hypoprothrombinemia. In afibrinogenemia the blood is incoagulable. A small amount of fibrinogen restores the coagulation time to normal.
The presence of heparin increases the coagulation time. The test is therefore useful in controlling the therapeutic action of this drug.
The senior author, in making a survey of the literature on hemorrhagic diseases in preparation of his monograph, was impressed by the significant and diverse contributions which Dr. George R. Minot made to this field of medicine. We feel honored to contribute this study to the collection of papers offered as a fitting tribute to Dr. Minot, who has so successfully and productively combined science and clinical medicine.
THE EFFECT OF INTRAVENOUS INJECTION OF TRYPSIN INHIBITOR ON THE COAGULATION OF BLOOD
Authors: TAGNON H. J. , SOULIER J. P. 
Published: October 2019

Abstract
1. The intravenous injection of a soya bean preparation containing a trypsin inhibitor into 2 dogs and 3 rabbits produced the following effects: prolongation of the clotting time and of the prothrombin time, and increase in the antiproteolytic activity of the blood plasma or serum.
2. Identical results were obtained in one experiment in which a crystallin trypsin inhibitor from soya bean was used.
3. The significance of these results is briefly discussed.
CYTOLOGY OF RABBIT THYMUS AND REGENERATION OF ITS THYMOCYTES AFTER IRRADIATION; WITH SOME NOTES ON THE HUMAN THYMUS
Authors: DOWNEY HAL , ENGSTROM RUBY 
Published: October 2019

Abstract
Thymocytes are genuine lymphocytes. The largest lymphocytes of lymph nodes do not occur in the thymus; the smallest ones with pacychromatic nuclei and scanty cytoplasm are more numerous in the thymus. Some lymphoblasts similar to myeloblasts occur in the rabbit thymus.
All three types of granulocytes develop from lymphocytes and to some extent from the mesenchymatous reticulum in the rabbit. In the rabbit the heterophil and eosinophil granules are acidophilic when first formed, while in the human thymus many have a basophilic quota as in the marrow. The reticulum is largely of epithelial origin and retains its epithelial characteristics in cytoplasm and nucleus. In the rabbit some mesenchymatous tissue is blended with the reticulum and may give origin to lymphocytes and granulocytes. The epithelium may form macrophages but does not differentiate to lymphocytes and other types of cells. In imprints from the rabbit the epithelial cells usually can be distinguished from those of the mesenchymatous reticulum. During regeneration following irradiation the latter tissue can be seen to form some lymphocytes locally; other lymphocytes enter the organ through the lymph vessels.
Imprints stained with May-Grünwald and Giemsa are of great value for detailed cytology of the thymus and for determining cell relationships. Sections of thymus fixed in Helly’s fluid, stained with methyl green and pyronin and dehydrated in dioxan are excellent for lymphocytes and the transitional stages resulting from their development from fixed mesenchymatous tissue during regeneration of the organ following exposure to x-rays.
THE EVENTS IN THE HEMOLYTIC CRISIS OF HEREDITARY SPHEROCYTOSIS, WITH PARTICULAR REFERENCE TO THE RETICULOCYTOPENIA, PANCYTOPENIA AND AN ABNORMAL SPLENIC MECHANISM
Authors: DAMESHEK WILLIAM , BLOOM MARVIN L. 
Published: October 2019

Abstract
The course of hereditary spherocytosis (congenital or familial hemolytic anemia) is subject to major or minor exacerbations or crises. Pancytopenia, reticulocytopenia, and extreme spherocytosis characterize the major crises, during which hypersplenic effects appear to play a major role. These are characterized by the combination of (1) an unusual degree of hemolysis with (2) inhibitory effects upon maturation and delivery of bone marrow cells. At the height of the crisis, an extreme degree of maturation arrest in erythropoiesis is present. Splenectomy, which is often urgently necessary, results in a very rapid increase in all the cellular elements of the blood, confirming the phagocytic and inhibitory effects of the abnormal spleen. Following splenectomy, no further crises occur. The presence of successive cases in the same family suggest the possible role of infection as a precipitating or trigger agent in initiating an abnormal splenic mechanism leading to crisis. The cause of the hereditary spherocytosis is commented upon and evidence bearing upon an autopsecific mechanism is discussed.
THE OCCURRENCE OF NORMOBLASTS IN THE PERIPHERAL BLOOD IN CONGESTIVE HEART FAILURE: AN INDICATION OF UNFAVORABLE PROGNOSIS
Authors: GROEN J. , GODFRIED E. G. 
Published: October 2019

Abstract
The authors recommend the search for normoblasts in the blood of patients with severe heart failure. When normoblasts are found, a marked interference with the oxygenation of the blood, either by pulmonary infarcts or thrombi inside the heart, is most likely to be present. It seems justifiable to consider the prognosis as very grave in these cases. This rule proved to hold even in those cases where, concomitant with an improvement in the heart failure, the normoblasts disappeared temporarily from the peripheral blood.
The Coagulation of the Blood. Investigations on a New Clotting Factor. BY PAUL A. OWREN. Oslo, J. Christian Gundersen, 1947
Authors: Taylor F. H. L. 
Published: October 2019

Abstract
An error was made in Dr. F. H. L. Taylor’s review of Dr. Owren’s book, "The Coagulation of the Blood," in the February issue of Blood (3: 229, 1948). The formulae as printed were incomplete and should have read:
See PDF for Equation
See PDF for Equation
See PDF for Equation
IS LEUKEMIA A DISEASE OF THE RETICULO-ENDOTHELIAL SYSTEM?
Authors: WISEMAN BRUCE K. 
Published: October 2019

Abstract
1. Evidence is given from case study of reticulo-endothelial disease supporting the concept that monocytic leukemia is one form of reticulo-endotheliosis.
2. On the basis of varied types of cell reactions seen in monocytic leukemia, it is suggested that all forms of leukemia may be hematologic varieties of reticulo-endotheliosis.