bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Necrosis Factor Alpha (TNF-a) Blockade and Risk of Lymphoma: Systematic Review and Analysis of Literature
Authors: Ramanarayanan Jeyanthi , Pahuja Shalu , Czuczman Myron S , Hernandez-Ilizaliturri Francisco J. 
Published: April 2020

Abstract
BACKGROUND: TNF-α plays a critical role in the regulation of cytokine mediated cancer immunosurveillance. Evidence suggests that depletion of TNF-α may result in abrogated anti-tumor immunity and increase in the risk of malignancies. Anti-TNF-α therapy (infliximab, adalimumab and etanercept) is known to halt the progression of certain inflammatory disorders and has been approved for the treatment of at least five autoimmune/inflammatory conditions. Given the widespread use of these biological agents, it is vital to explore the associated increased risk of malignancies especially lymphoma.
OBJECTIVE: Risk of lymphoma associated with anti-TNF-α therapy is controversial in rheumatoid arthritis (RA) and has not been extensively studied in other inflammatory disorders. With the expanding role of anti-TNF-α therapy, we evaluated the risk of lymphoma among all approved indications for which they are currently in use.
METHODOLOGY: We conducted a systematic electronic search of MEDLINE using the terms TNF-α, infliximab, adalimumab, etanercept, rheumatoid, psoriasis, arthritis, inflammatory bowel disease, ankylosing spondylitis from January 1998 to December 2007. Studies analyzed were restricted to those in English language, full text published articles, randomized controlled trials (RCT), meta-analysis (MT), review articles, extension studies, reports from national databases (ND) and postmarketing surveillance studies. Risk of lymphoma from ND was obtained as odds ratio with 95% confidence interval. Incidence of lymphoma reported from RCT was analyzed as percentage fraction of the total number of patients enrolled in the study and follow up.
RESULTS: Overall 51 studies (2 MT, n=10,370; 4 ND, n=29,099 and 45 RCT, n=54,637) that included anti-TNF-α therapy in inflammatory disorders were analyzed. Treatment/follow up period were variable from 12 weeks to 8 years. Ten patients (0.09%) from MT treated with anti-TNF-α therapy developed lymphoma vs 0 in the non-anti-TNF-α group. Report from one of the 3 ND showed an increased risk (11.5 RR 95% CI 3.7–26.9) of lymphoma among the anti-TN-α exposed group. Among the RCT, 16 patients (0.02%) in the anti-TNF-α group developed lymphoma vs 3 (0.005%) in the control group.
CONCLUSION: Existing data suggests that anti-TNF-α therapy in rheumatoid arthritis is associated with an increased risk of lymphoma but this may be attributed to the severity of the disease itself. Among other inflammatory disorders, a rise in lymphoma risk could not be established. Whether anti-TNF-α therapy in the long term can in fact decrease the incidence of lymphoma by altering the disease severity remains to be determined.
MYST3/NCOA2-Induced Acute Myeloid Leukemia in Transgenic Fish
Authors: Zhuravleva Julia , Paggetti Jérôme , Martin Laurent , Hammann Arlette , Solary Eric , Bastie Jean-Noël , Delva Laurent 
Published: April 2020

Abstract
The MYST3/NCOA2 (MOZ/TIF2) fusion gene generated by the inv(8)(p11q13) chromosomal abnormality was described in a specific subgroup of acute myeloid leukemias (AML) that represents less than 5% of AML4/5. This abnormality fuses MYST3 (MOZ), a member of the MYST family of histone acetyl-transferases (HAT) to NCOA2 (TIF2), a member of the p160 HAT family. The transforming properties of MYST3/NCOA2 were demonstrated in mouse committed myeloid progenitors in vitro and in vivo. Hematopoiesis is very similar in zebrafish and in higher vertebrates. Homologues of a large number of genes involved in mammalian myelopoiesis were identified in this animal model. We have recently shown that ncoa2 (tif2) played a role in zebrafish primitive hematopoiesis. This animal also represents a model for investigating leukemogenesis. Transgenic expression of rag2-EGFP-mMyc or rag2-ICN1-EGFP induces a T-cell acute lymphoblastic leukemia (ALL) whereas transgenic expression of the ETV6/RUNX1 fusion gene induces a B-cell type ALL. We generated a transgenic zebrafish in which the MYST3/NCOA2 fusion gene was expressed under control of the spi1 (pu.1) promoter. An AML developed in two of 180 MYST3/NCOA2-EGFP-expressing embryos, 14 and 26 months after injection of the fusion gene in a one cell embryo, respectively. This leukemia was characterized by an extensive invasion of kidneys by myeloid blast cells. This model, which is the first zebrafish model of acute myeloid leukemia, demonstrates the oncogenic potency of MYST3/NCOA2 fusion gene.
Aberrant PDGFRA Signalling Is Sustained by An Autocrine Loop in Peripheral T-Cell Lymphoma Not Otherwise Specified
Authors: Piccaluga Pier Paolo , Rossi Maura , Esposito Aurora , Tazzari PierLuigi , Ricci Francesca , Agostinelli Claudio , Righi Simona , Gazzola Anna , Went Philip , Alviano Francesco , Bagnara Gian Paolo , Zinzani P.L. , Pileri Stefano A. 
Published: April 2020

Abstract
Background. Peripheral T-cell lymphoma not otherwise specified (PTCL/NOS) is the most common T-cell lymphoma; however, it remains a complex entity showing great variety regarding morphology, immunophenotype and clinical behaviour. Recently, gene expression profiling (GEP) revealed PDGFRA as possible PTCL-associated molecule, by nominating it as potential therapeutic target.
Aims and Methods. We investigated the possible determinants of PDGFRA activity in PTCL/NOS. We performed GEP of 28 PTCLs/NOS and 20 samples of normal T-cell subpopulations, by using the Affymetrix HG-U133 2.0 plus microarray. Moreover, we built tissue-microarrays (TMAs) including 145 PTCLs/NOS for protein analyses. The PDGFRA locus (4q1.1–4q1.3) was studied by FISH on those TMAs, while direct sequencing of all PDGFRA exon and introns as well as of the promoter region was performed in 90 cases. Immunohistochemistry (IHC) and ELISA were adopted in order to study the expression of PDGF-A, PDGF-B and PDGF-C on tissue sections and in supernatants from PTCL/NOS cell cultures, respectively. Finally, the expression of PDGFRA and its activated (phosphorilated) form, p-PDGFRA, was assessed by IHC on TMAs, and by flow-citometry in PTCL/NOS cultured cells before and after the exposure to an anti-PDGF ligand neutralizing antibody (R&B System).
Results. First, GEP showed over-expression of PDGFRA in all tested PTCLs/NOS, while IHC confirmed the expression of PDGFRA and p-PDGFRA. FISH, SNPs analysis and direct sequencing showed preserved integrity of PDGRA locus. We then studied PDGF-A, PDGF-B and PDGF-C, which turned out to be expressed and secreted by PTCL/NOS cells. In order to verify the hypothesis of an autocrine loop, we tested whether the remotion of PDGF ligands from the supernatants of cultured PTCL/NOS cells determined PDGFRA de-phosphorilation. Notably, 48h after the exposure to 20 mg of anti-PDGF antibody, we already appreciated a significant effect with reduction of PDGFRA phosphorilation up to 75%.
Conclusions. Taken together, our data demonstrate that PDGFRA activity is sustained by an autocrine loop in PTCL/NOS.
Oral Contraceptive-Associated Thromboembolism. A Retrospective Analysis of Thrombophilic Work-out and Long Term Follow up in 57 Cases
Authors: Papadakis Emmanouil , Efremidou Smaragda , Kartsios Haris , Mpraimi Margarita , Kokoviadou Kiriaki , Loukidis Konstantinos , Papaioannou Georgia , Korantzis Ioannis 
Published: April 2020

Abstract
Introduction: The increased risk of venous thrombosis in women taking oral contraceptives (OCs) has been recognized since the early 1960s. Coexistence of hereditary risk factors appears to have an additive effect. Women under OCs that carry the factor V Leiden mutation have a 35-fold increased risk of thromboembolic events compared to women without the mutation who are not on OCs. Evaluation of family and personal history is the mainstay of prophylaxis prior to OC administration, but often family thrombophilia or thromboembolic (TE) events are not reported prior to OCs prescription.
Patients-Methods: Fifty-seven women with a median age of 28 (21–48) years, which suffered OC-associated TE, were studied. The median period of OC therapy prior to TE event was 2 months (0.5–60). Fifty-five of them experienced VTE while 2 suffered stroke. Leg thrombosis was the most common clinical finding [37/55 (67,2%) patients] Apart from personal and family history, Thrombophilia investigation included measurement of : serum Homocysteine, Antithrombin, Protein C and S, Lipoprotein (a), Activated Protein C (APC) resistance, antiphospholipid antibodies and lupus anticoagulant. In addition the presence of FV Leiden, FII 20210 GA mutations and MTHFR 677 CT polymorphism were determined.
Results: A high prevalence of the factor V Leiden mutation was detected in the study group; 50% had APC-resistance test positive, 26 (45%) patients were found to be heterozygous and 3 (5,2%) homozygous for the FV Leiden mutation. Lp(a) elevation was observed in 19,3% and Homocysteine elevation in 15,8% of patients. In 9 women (15,8%) both family history and thrombophilic profile were negative. Serious VTE events (2 abdominal and 6 CNS thromboses) were observed only in the Leiden subgroup. During the follow up period ranging from months to 18 years, 3 women (6,25%) experienced a miscarriage and 14 suffered additional VTE events (25%) and they are currently on permanent anticoagulation.
Conclusions : Universal thrombophilia screening of women prior to prescription of OCs is not advisable as it does not appear to be cost effective. However, screening certain subgroups, such as women with a known personal or family history, may be of great value. If a full thrombophilic profile can’t be performed, a mere activated protein C resistance test, that reflects the presence of the factor V Leiden mutation, may provide an easy and cheap way of identifying and consulting properly women at higher risk for VTE prior to OC use. Women with OC-associated VTE and thrombophilia carry a substantial recurrence risk that persists for years.
Retinal Artery Occlusion and Other Arterial Thrombotic Events in Women Using Yasmin
Authors: Shum Merrill K , Nacopoulos Dimitrios A 
Published: April 2020

Abstract
The third-generation combined oral contraceptive pill, Yasmin®, which contains 30 ug ethinyl estradiol and 3 mg of drospirenone, has been marketed as safe and effective, but the risks of arterial thrombotic events in women using Yasmin® are unknown. We report a case of retinal artery occlusion in a woman using Yasmin®, and review the literature for other cases of arterial thrombotic events in women taking Yasmin®. An extensive search using Pubmed, Ovid, and Medline, revealed three previously reported cases of arterial thrombotic events, in women using Yasmin® (see table below). Similar to the three prior cases, our case study had no known acquired or hereditary thombophilic conditions. Unlike the previous three cases, our subject did not smoke and developed her arterial thrombus late, approximately three years after initiating Yasmin®. It appears that the risk for arterial thrombotic events may occur at anytime. Large scale studies determining relative incidence, as well as post-marketing adverse effects are needed to determine risk and incidence while using Yasmin®.
Studies reporting arterial thrombotic events in women using Yasmin®
Author Year Age of patient Type of thrombosis Days on OC before thrombosis Associated risk factors Comments Vaya, et al. (1) 2003 21 TIA 15 days Smoking (15/day) Apparent recovery Cabou, et al. (2) 2006 33 MI 15 days Smoking (6/day), surgery for ectopic pregnancy 15 days before MI Pt had taken 2nd generation OCP in the past without complications, recovered Girolami, et al. (3) 2007 18 Central retinal artery occlusion 10 days Smoking (8/day) No recovery, two years after event Shum, et al. 2008 21 Central retinal artery occlusion 3 years None Pt had taken 1st generation OCP for 2 years without complications, not yet recovered after 4 months
Metylenetetrahydrofolate Reductase Polymorphism and Venous Thrombosis in Children
Authors: Luciani Matteo , Pansini Valeria , Coletti Valentina , Funaro Daria , Soldati Massimiliano , Pancotti Simona , Falappa Piergiorgio , De Rossi Giulio 
Published: April 2020

Abstract
The venous thromboembolism is a serious and complex pathological condition especially for its potential complications. It is related to both congenital and acquired factors. Among the congenital factors, different mutations have been identified leading to a reduced activity of enzymes (even higher than 50%) involved in the homocysteine-methyonine methabolic pathway, such as the methylenetetrahydrofolate reductase enzyme (MTHFR).
The homozygotic TT genotype is found in approximately 10–12% of the population and is associated with a 25% higher homocisteine level in these patients than those without this mutation. The heterozygotic genotype is found in 40% of the population. The aim of this study is to define in children the correlation between venous thrombosis and MTHFR mutations. Between december 2002 and april 2008 nine children aged between 1–132 months were admitted in the Department of Hematology of Children Hospital Bambino Gesù in Rome. They were affected by deep venous thrombosis and were submitted to thrombophilic screening and vascular imaging. The MTHFR polymorphism C677CT was found in all the patients (four in homozygosis and seven in heterozygosis) and also in their parents. Four heterozygous and three homozygous patients presented increased plasmatic and urinary levels of homocysteine. Since venous thrombosis was only referred in the clinical history, two patients did not received treatments. Nine were treated with low molecular weight heparin (enoxaparin 100 U/kg s.c. × 2 daily), then seven continued the treatment with oral anticoagulant for 6–12 months and all of them performed long term profilaxis with folic acid and B group vitamins. Only one patient presented further thrombotic event and restarded the oral anticoagulant therapy. These data confirm that the measurement of homocysteinemia and MTHFR may be indicated in unexplained idiopathic venous thrombosis or recurrent episodes or venous thrombosis occurred at an early age or at an uncommon site. It is to be discussed whether to perform anticoagulant profilaxis in all patients with MTHFR mutation, in homozygosis or heterozygosis, with or without hyperhomocysteinaemia, with previous thrombotic events, with other thrombotic risk factors (pregnancy, oral contracceptives, sepsis and immobilization). In addition in presence of hyperhomocysteinemia, it might be reccomended to perform therapy with folic acid and B6 vitamin.
The Prevalence of Anemia in Rio Grande Do Sul, Brazil: Is Iron Deficiency the Silent Burden Hidden Behind “Normal” Anemia?
Authors: Silla Lucia , Zelmanowicz Alice , Mito Ingrid , Daudt Liane , Bem Carlos do , Alves Marta , Lehuguer Denise , Fridrisch João , Bittar Christina , Fisher Gustavo , Fogliatto Laura , Paz Alessandra , Bittencourt Rosane , Bortolini Gisele , Brouwers Larissa , Shilling Marco , Michalowski Mariana , Hellwig Tania 
Published: April 2020

Abstract
We ran a study on the prevalence of anemia in the state of Rio Grande do Sul (RS), southern Brazil. RS is in a sub-tropical Latin American area, near Uruguay and Argentina. There is no Malaria, a low prevalence of hemoglobinopaties, and HIV/AIDS.
METHODS: Capillary blood of children less then 7 and women from 14 to 30 years of age were tested. Socioeconomic status was determined utilizing the classification designed by the Brazilian Association of Market Research Agencies for this purpose. A second sample of 1 year old children was submitted to total blood cell count and serum ferritin determination, and in a third group of individuals, total blood count was done along with stool parasitic analysis.
RESULTS: A total of 2198 children and 1999 women with capillary blood measured were analyzed. The median prevalence of anemia in the whole state and the median hemoglobin concentration was 45, 4% and 9.90g/dl for children, and 36.1% and 11 g/dl for women, respectively. Of the aforementioned group, before two years of age, 76% were anemic, and anemia prevalence decreased with age, suggesting a nutrition deficiency. There were very few cases of severe anemia. A significant percentage of children and women belong to the middle class, with access to food and medical care. Of the 356 children tested at one year of age, 67% were anemic and of these, 90% had ferritin &lt; 15μg/L. In the third group of individuals, 31% of 424 children less then 6 years of age were anemic and of these, only 13% tested positive for parasitic infection.
CONCLUSION: The prevalence of iron deficiency anemia is very high and constitutes a severe public health problem for 1 year old children in RS, and probably for those younger then 7, and for fertile women as well, irrespectively of their socioeconomic level. Micronutrients supplementation has being neglected in RS health system. The definition of anemia plays a central role in this and has to be addressed if we want to overcome the biologic factors involved in childhood psychosocial development in Brazil.
An IgM Lambda Monoclonal Antibody in a Patient with Anti-Pr Cold Agglutinin Causing Erythrocyte Agglutination and Catastrophic Thrombosis
Authors: Kwaan Hau C. , McMahon Brandon , Ruch Joshua , Weiss Ivy 
Published: April 2020

Abstract
Erythrocyte agglutination causing microvascular occlusion is a rare albeit clinically significant event. This is seen in cold agglutinin disease and in cerebral malaria caused by Plasmodium falciparum. We studied a patient with autoimmune hemolytic anemia, characterized by massive hemolysis and the presence of both an anti-Pr antibody and a cold hemagglutinin. In addition, he suffered from catastrophic mesenteric ischemia necessitating surgical resection and extensive and multiple ischemia strokes. His surgical specimens, including colon, ileum and gall bladder, were studied with informed consent. Eluate from his agglutinated erythrocytes showed that he had an IgM lambda monoclonal antibody against the Pr antigen. The patient’s peripheral blood showed extensive erythrocyte agglutination that was worse at cold temperatures. H&E staining of the colon and ileum showed ischemia and necrosis with widespread microvascular occlusion caused by agglutinated erythrocytes. To characterize the intravascular agglutinated erythrocytes, immunoperoxidase staining was done and positive for IgM and lambda light chain and negative for IgG and kappa light chain. We thus concluded that the cold agglutinin on the intravascular agglutinated erythrocytes was an IgM lambda. To investigate why the circulating agglutinated erythrocytes resulted in widespread microvascular occlusion, we studied adhesive molecules including CD 62E (E-selectin), CD62P (P-selectin), CD54 (ICAM-1) and CD 106 (VCAM-1) and found all of them expressed on the agglutinated erythrocytes within the occluded vessels and on the endothelial cells of the involved vessels. The data suggests that the endothelial cells were activated at the site of vascular occlusion, thereby promoting adhesion of the agglutinated erythrocytes to the vascular endothelium.
Shape Recovery of Human Crenated Erythrocyte Ghosts Depends on the Cytoplasmic Endoskeletal Actin Filaments
Authors: Terasawa Kazutaka , Taguchi Takehito , Momota Ryusuke , Naito Ichiro , Ohtsuka Aiji 
Published: April 2020

Abstract
Previously, we showed the human erythrocyte cytoplasmic endoskeleton composed of actin filaments and intermediate filaments [Terasawa K, et al. Arch. Histol. Cytol.2006;69:326–340]. The present study aims to determine whether endoskeletal actin filaments contribute to regulate the shape recovery of human erythrocytes. We prepared two types of ghosts: prefixed ghosts which contain endoskeletal network and non-fixed usual ghosts which lack endoskeletal network. To prepare prefixed ghosts, fresh erythrocytes were mildly fixed with 2 % paraformaldehyde and 0.05 % glutaraldehyde in phosphate buffered saline and haemolysed by mild hypotonic Tris buffer with 2 mM Mg-ATP. These prefixed ghosts contained an endoskeletal network which could change their shape quickly by Mg-ATP. In transmission electron microscopy, all the spherical and crenated prefixed ghosts possessed the endoskeletal network as an electron dense matter. Gold particles immuno-labeled for beta actin dispersed over the whole endoskeleton in both crenated and discoid prefixed ghosts. Moreover, cytochalasin B, a blocking agent of fast growing end of long actin polymer, inhibited crenated to discoid shape transition in prefixed ghosts. In non-fixed ghosts, addition of cytochalasin B did not affect recovery to the original shape. Thus, these results suggest that shape transition induced by Mg-ATP is driven through the action of the endoskeletal actin network.
Serum Prohepcidin Levels in Infants with Anemia of Inflammation and Iron Deficiency Anemia
Authors: Park Eun Sil , Kim In-Suk , Lim Jae-Young 
Published: April 2020

Abstract
Backgroud . The aims of this study were to measure the serum levels of prohepcidin in anemic and non anemic infants and to evaluate the correlation between prohepcidin and iron parameters and inflammatory cytokines.
Procedure. One hundred and sixty nine patients aged from 6 months to 24 months were enrolled and divided into 4 groups according to hemoglobin and serum ferritin (SF). Routine hematologic labs, soluble transferrin receptor (sTfR), serum prohepcidin, C reactive protein (CRP), and interleukin-6 (IL-6) were assessed. The subgroup of anemia of inflammation (AI) was defined as Hb &lt;11 g/dL and SF &gt;50 μg/L, the subgroup of iron deficiency anemia (IDA) as Hb &lt;11 g/dL and SF &lt;12 μg/L, the normal group as Hb ≥11 g/dL and SF ≥12 μg/L, and the unclassified anemia group (UCA) as &lt;11 g/dL and SF 12–50 μg/L.
Results. The prohepcidin levels ranged from 38.86 to 874.25 ng/mL throughout all the infants (258.60±130.03 ng/mL) but were significantly lower in the AI group than in the normal group (201.93±71.74 vs 299.97±120.68 ng/mL, P=0.007). However there was no significant difference between anemic subgroups. Prohepcidin levels were positively correlated with CRP (r=0.400, P=0.048) in the AI group and were negatively correlated with sTfR in the UCA group (r=−0.376, P=0.022). However in both groups there were no independent predictors in multiple regression analysis.
Conclusions. This study examines the prohepcidin levels in infants with anemia and without anemia. The prohepcidin levels of anemic infants were significantly lower than those of infants without anemia. However there was no correlation between prohepcidin and inflammatory cytokines or iron parameters in the groups of AI and IDA, thus we cannot differentiate between them using prohepcidin levels.