bluuebunny/crossref_metadata_2025_split huggingface dataset:
Escalating Costs of Cancer Treatment: The Local Effect of a Global Reality
Authors: Souza Danielle Leão 
Published: April 2020

Abstract
While incidence of cancer has been increasing worldwide, so has the cost of cancer treatment. As newer anti-cancer drugs and diagnostic tools have become available, the results of pharmacoeconomic studies have also become more important in the recent years, in guiding cancer treatment policies and reimbursement decisions.
In Brazil, there will be more than 466,000 new cases of cancer in 2008. In this very populated developing country, health policy makers and administrators of private and public health services are becoming increasingly concerned about the cost of cancer treatment.
This health economic project utilized the database of Unimed, a private health care plan which is the biggest in the southern Brazil. The Unimed health plan has over 45,000 clients & 300,000 users in Cascavel region.
The cost of oncology drugs from 2003 to 2007 at two cancer treatment centers in the region was analyzed. The results showed a progressive increase in the expenses at these centers.
Over the period of 5 years, the claims for oncology drug increased 4 fold in one center, and an astronomical 13 fold in the other center. By 2007 the total cost of oncology drugs exceeded US$ 600,000 & US$ 1 million in these 2 oncology centers. Details of the population treated, average cost per patients etc over this period will be presented in the full poster.
While only about 20% (40 million) of the population of Brazil are covered by such private health plans, the dramatic increase of cancer treatment costs seen within this health plan of a single patient population puts in perspective the concerns and funding pressures facing health plans in Brazil, and perhaps the rest of the world.
There is a need for more robust pharmacoeconomic studies to provide clearer treatment guidance and for formulating healthcare policies, so that patients receive better treatment outcomes. A comprehensive Health Technology Assessment processes may also help to streamline how private and state health plans cover such newer treatments, thereby enabling them to provide optimal level of care and services to their patients.
In conclusion, these local Brazilian data confirms that escalating cost of cancer treatment is also a reality in the developing world. Without the support of strong health economic data, it may become increasingly challenging for cancer patients in Brazil to have access to these newer cancer medications.
Direct Confirmation of Quiescent Property of AML Stem Cells by Showing Markedly Decreased Plating Efficiency in Single Leukemic Stem Cell Culture
Authors: Shin Myung-Geun , Kim Hye-Ran , Kim Chang-Soo , Kim Hyeoung-Joon , Kook Hoon , Kee Seung- Jung , Kim Soo-Hyun , Shin Jong-Hee , Suh Soon-Pal , Ryang Dong-Wook 
Published: April 2020

Abstract
Cancer stem cell, recently discovered to exist in colon cancer and brain tumor, is resistant to anti-cancer drugs and radiotherapy, demanding the development of new drugs and treatment strategies targeting tumor stem cells. Leukemic stem cell (LSC) has been accused to play a pivotal role in pathogenesis of hematological malignancy such as acute myeloblastic leukemia (AML). Various anti-cancer medicines, particularly anti-proliferative agents, have been ineffective in treating LSC due to its slower division process and longer interphase compared to normal stem cell and hematopoietic cell. This study comparatively examined growth and proliferation capacity (plating efficiency) of clonogenic hematopoietic progenitors and LSC from healthy donors and AML patients using single cell sorting and culture system (BD FACS Aria cell sorter; BD Biosciences, San Jose, CA). A total of 384 normal hematopoietic stem cells (CD34+CD38+/CD38−) were obtained from peripheral bloods and cord bloods donated by four donors using single cell sorter, and individual single cells were cultured in 96-well plates with each well containing 100ul of serum media, 100ng/ml of stem cell factor, 100ng/ml of Flt-3, 100ng/ml of thrombopoietin and 50ng/ml of G-CSF for five days. 768 single LSC (CD34+CD38−) and 384 single CD34+CD38+ cells were obtained from three AML patients. Growth and proliferation capacities of normal hematopoietic stem cell and LSC were determined in terms of plating efficiency (number of the wells in which more than two cells grew/total number of cells in 96-well plate culture × 100). Plating efficiency of individual normal single hematopoietic stem cells varied between samples. Eighty eight out of 192 single stem cells originated from cord blood grew into more than two cells, yielding plating efficiency of 45.8% and cells from the peripheral blood of two healthy donors 30.2% (58/192). In contrast, single LSC originated from the AML patients showed significantly lower plating efficiency with 14.6% (42/288), 3.6% (7/192) and 8.0% (23/288). These results directly confirmed quiescent and slowly dividing properties of LSC. In addition, plating efficiency of normal hematopoietic stem cells was shown to vary between their originating locations in healthy donors.
In Vitro Differentiation of Human Placenta Derived Mesenchymal Stem Cells into Dopaminergic Cells
Authors: Dongmei He , Li Chen , Yuan Zhang 
Published: April 2020

Abstract
Mesenchymal stem cells (MSCs) constitute an interesting cellular source to promote brain regeneration after Parkinson diseases. Compared with other stem cells, MSCs derived from human placenta have significant advantages and greater potential for immediate clinical application. The aim of this study was to investigate whether human placenta mesenchymal stem cells(hpMSCs) could be induced to differentiate into dopaminergic cells in vitro. MSCs from human placenta were isolated by digest and density gradient fractionation. Cell surface glycoproteins of these hpMSCs were analyzed by flow cytometry. These hpMSCs were cultured under conditions promoting differetiation to osteoblasts and adipocytes. Using a cocktail that includes basic fibroblast growth factor(bFGF), all trans retinoic acid(RA), ascorbic acid(AA),3-isobutyl-1-methylxanthine(IBMX), hpMSCs were induced in vitro to become dopamine (DA) neurons. The expression of mRNA of nestin and tyrosine hydroxylase(TH) genes known with significant associated with dopaminergic neuron differentiation from the induced hpMSCs was assayed by RT-PCR. The expression of proteins of nestin, dopamine transporter(DAT), neuronal nuclear antigen(NeuN) and TH was determined by immunofluorescence. The synthesized and secreted DA by induced hpMSCs was determined by ELISA. We found that hpMSCs exhibited fibroblastoid morphology. Flow cytometric analyses showed that the hpMSCs were positive for CD44 and CD29, negative for CD34, CD45, CD106 and HLA-DR. Moreover, they could be induced into adipocytes and osteocytes. When hpMSCs were induced with bFGF, RA, AA, IBMX, the MSCs showed a change of neuronal-like cells in morphology. The induced cells express nestin and TH mRNA. The induced MSCs also express nestin, DAT, NeuN, and TH protein. ELISA showed the induced MSCs synthesized and secreted DA. Our results suggest that MSCs from human placenta have the ability to differentiate into dopaminergic cells in vitro.
The Effect of Mesenchymal Stem Cells as a Cell Therapy in Renal Ischemia
Authors: Hong Dae Sik , Park Seongkyu , Won Jong-Ho , Kim Chan Kyu , Lee Sang Chul , Lee Kyu Taeg , Bae Sang Byung , Park Hee Sook 
Published: April 2020

Abstract
Introduction: The most commonly used therapeutic targets in nephrology are the reduction of injury, the delay of progression, or renal replacement therapy. Many animal and human studies demonstrated the role of stem cells in repair and regenerations of kidney. Mesenchymal stem cells (MSCs) have shown to improve outcome of acute renal injury models. It is controversial whether MSCs can reduce injury following a toxic/ischemic event and delay renal failure in chronic kidney disease. We evaluated the hypothesis that the treatment with MSCs could improve renal function and attenuate injury in chronic renal failure (CRF).
Materials and methods: Sprague-Dawley female rats (8 weeks old, 182.2 ± 7.2g) were underwent modified 5/6 nephrectomy. Rats in the MSC group received an injection of MSCs (1 × 106 cells) via tail vein 1 day after nephrectomy. Blood and urine samples were collected after 7 days and every month thereafter. The kidneys of rats were removed for histologic evaluation after 24-hr urine collection and blood sampling. The Y-chromosome stain using fluorescent in situ hybridization was performed to verify the presence of male MSCs in the kidney of female recipients.
Results: No significant differences in blood urea nitrogen and creatinine concentration were observed between MSC group and untreated CRF group. However, the weight gain and creatinine clearance in the MSC group were greater than those of the CRF group. Proteinuria in the MSC group was less after 4 months. Y chromosome was detected in the kidney of MSC group. Although no significances were observed between two groups, the histologic analysis suggests that MSCs have positive effect against glomerulosclerosis.
Conclusions: These results suggest that MSCs help preserve renal function and attenuate renal injury in CRF.
Elevated Endothelial Progenitor Cells during Painful Sickle Cell Crisis
Authors: Nur Erfan , van Beem Rachel T. , Zwaginga Jaap Jan , Landburg Precious , van Beers Eduard J. , Duits Ashley , Schnog John-John , Lommerse Ingrid , Van der Schoot C. Ellen , de Boer Hetty C. , Brandjes Dees P.M. , Biemond Bart J. 
Published: April 2020

Abstract
Background: Sickle Cell Disease (SCD) is characterized by microvascular occlusion leading to an ischemia-induced pro-angiogenic response. Circulating endothelial progenitor cells (EPCs) play an important role in neovascularisation and decreased EPC numbers are associated with poor outcome in cardiovascular disease.
Aims: To determine the numbers of circulating EPCs in patients with SCD during steady state and painful crisis and to assess the association of EPC numbers with serum levels of humoral growth factors (stromal derived growth factor-1α (SDF-1α), erythropoietin (EPO), vascular endothelial growth factor (VEGF), placenta-induced growth factor (PIGF), interleuking-8 (IL-8), soluble vascular adhesion molecule-1 (sVCAM-1)).
Methods: Numbers of circulating EPCs, defined as CD45dim/CD34+ cells expressing vascular endothelial growth factor receptor-2 (VEGF-R2), and serum levels of humoral factors were measured consecutively in 66 patients in steady state, 23 patients during painful sickle cell crisis and 13 age- and race-matched healthy controls.
Results: While circulating EPC numbers were comparable between healthy controls and sickle cell patients in steady state, they were significantly increased in patients during sickle cell crisis. EPC numbers correlated significantly only to serum SDF-1α levels during painful crisis.
Conclusion: Sickle cell crisis is characterized by elevated circulating EPC numbers further supporting a pro-angiogenic state in SCD. SDF-1 may play a role of importance in EPC mobilisation during sickle cell crisis.
Identification of Multiple Oxidative Post-Translational Modifications of Plasma Albumin in Patients with Pulmonary Hypertension of Sickle Cell Anemia
Authors: Odhiambo Adam , Perlman David , Steinberg Martin , Costello Catherine E. , McComb Mark E. , Klings Elizabeth 
Published: April 2020

Abstract
Background: Pulmonary hypertension (PH) in sickle cell anemia (SCA) is characterized by decreased nitric oxide bioavailability; which may, in part, be related to increased oxidative stress. It is possible that via protein post-translational modifications, oxidants are able to affect both protein structure and function. We hypothesized that, in patients with SCA and PH, oxidative post-translational modifications (PTMs) occur on plasma proteins and are important in disease pathogenesis. We previously reported the identification of one PTM, a malondialdehyde adduct on peptide 146–159 of albumin and sought to do a more extensive evaluation of this protein to determine the presence of other abnormalities.
Methods: Plasma was obtained from subjects with:
SCA and PH (n=5); SCA steady-state without PH (n=4); Pulmonary Arterial Hypertension (PAH) (n=4); no evidence of cardiopulmonary disease (n=4).
Platelet-poor plasma was separated into albumin-enriched and albumin-depleted fractions. The albumin-enriched fraction was subjected to proteolytic digestion by trypsin and studied by matrix-assisted-laser desorption/ionization (MALDI) mass spectrometry (MS) and liquid chromatography (LC)-MS/MS tandem mass spectrometry. Proteomic analyses were performed on all samples and post-translational modifications characterized by MS/MS.
Results: We have characterized several additional peptides of albumin from patients with PH of SCA that bear lipid peroxidation and glycation adducts. Our comprehensive LC-MS/MS results have allowed us to identify 4-hydroxynonenal (HNE), hexose (HEX) and malonyl adduction at numerous, distinct cysteine, histidine, lysine, and threonine albumin residues.
Conclusion: Increased oxidant burden and altered redox biology is characteristic of PH in SCA. Plasma proteins, such as albumin, are a target for oxidants and changes in their structure may play a role in disease pathogenesis.
Benzocaine Induced Methemoglobinemia a Potentially Life Threatening Complication after Transesophageal Echocardiogram
Authors: Sreenivasappa Shylendra B , Yim Barbara , Catchatourian R. 
Published: April 2020

Abstract
Methemoglobinemia is a potentially life threatening medical condition that occurs due to increased methemoglobin production or decreased elimination. Methemoglobin is a derivative of hemoglobin in which the normal ferrous (Fe2+) iron state is oxidized to the ferric (Fe3+) state. This oxidized hemoglobin is unable to bind oxygen, hence reducing he oxygen carrying capacity of blood. The clinically presentation is characterized by cyanosis, low pulse oximeter reading and normal arterial PO2. Topical use of benzocaine a local anesthetic widely used in endoscopic procedures is one of the incriminated causes of acquired methemoglobinemia.
We present two cases of patients (pts) who developed methemoglobinemia after benzocaine spray for a transoesophageal echocardiogram. One pt was 50 year old male and other 30 year old female. Both had a methacilline resistant Staphylococcus Aureus bacteremia secondary to septic arthritis, they under went a transesophageal echocardiogram to rule out endocarditis. Topical local anesthesia used was benzocaine 20%. About 10–15 min after local anesthesia they desaturated to the mid 80’s and they developed cynosis, they were intubated. On Blood gas analysis methemoglobin. was elevated 38.4% (male pt) and 18.9% (Female pt). They were given methylene blue at the dose of 2mg/kg intravenously over 10 minutes. Cyanosis corrected with in an hour. Methemoglobin level corrected to normal after 3 hours after administration of methylene blue. There were no adverse events with administration. The Glucose 6 Phosphate Dehydrogenase enzyme level was tested and was negative.
In conclusion benzocaine induced methemoglobinemia should be considered in pts under going Transesophageal Echocardiogram when cyanosis develops that is unresponsive to oxygen. Diagnosis can be confirmed by arterial blood gas analysis. If identified early this potentially life threatening condition can be treated with methylene blue with minimal complications and good outcomes.
Prognostic Analysis of Hodgkin Lymphoma (HL) in JAPAN
Authors: Okamoto Rumiko , Itoh K. , Kinoshita T. , Watanabe T. , Yoshimura K. , Chou T. , Ogura M. , Hirano M. , Asaoku H. , Kurosawa M. , Maeda Y. , Omachi K. , Moriuchi Y. , Kasai M. , Ohnishi K. , Takayama N. , Morishima Y. , Tobinai K. , Kaba H. , Yamamoto S. , Fukuda H. , Kikuchi M. , Yoshino T. , Matsuno Y. , Hotta T. , Shimoyama M. 
Published: April 2020

Abstract
Background: Since the incidence of HL in Japan is approximately one-third of that in western countries, there are few studies on validation of international prognostic score (IPS) in Japanese patients (pts) with HL.
Patients and Methods: JCOG-LSG conducted 2 multicenter phase II trials for advanced HL, including ABVd (JCOG9305) and ABV followed by involved-field radiotherapy (JCOG9705). Because dacarbazine was highly emetic, and not approved for HL in Japan in those days, the dose of dacarbazine was reduced to a two-thirds (250 mg/m2) of that in original ABVD regimen in ABVd, and in ABV with increased dose of doxorubicin, dacarbazine was not utilized. Among the whole 200 enrolled pts, histopathological specimens from 181 pts were reviewed by 6 hematopathologists and consensus diagnosis of HL was made in 167 (92.3%), according to the WHO classification. Major eligibility criteria of the trials were age between 15 and 69, ECOG performance status of 0 to 3, and clinical stage of II, III or IV in JCOG9305, and IB, IIB, III or IV in JCOG 9705.
Results: 5-year survival of the 167 patients was 88.3%. Histopathological distributions of 167 pts with HL were similar with those in western countries; 2 nodular lymphocytic predominance (1.2%), 115 nodular sclerosis (68.9%), 3 lymphocyte-rich (1.8%), 34 mixed cellularity (20.1%), 7 lymphocyte depletion (4.2%), and 6 unclassified (3.6%). IPS was poorly fitted for the overall survival (OS), mainly because of too good prognosis of patients with IPS-grade 6. Seven unfavorable prognostic factors for OS identified by the univariate analysis were male sex, high β2 microglobulin, B symptoms, high LDH, high alkaline-phosphatase, clinical stage of III or IV, and histopathological subtype (mixed cellularity or lymphocyte depletion). Excluding β2 microglobulin from analysis because of only 105 available data, male sex [HR 3.30 (95%CI: 1.15–9.52, p=0.027) ] and high LDH [HR 2.41 (95%CI: 1.07–5.43, p=0.034)] were significant independent risk factors in a multivariate analysis.
Conclusions: Our study suggests that male sex and high LDH might be important prognostic factors in OS of pts with HL. Simple prognostic model for HL, including sex and LDH, was suggested.
The Significance of the Variants Erythrovirus in Patients with Cytopenias of Unknown Origin
Authors: Garcia Sheila Oliveira , Pereira Juliana , Sanabani Sabri , Neto Walter Kleine , Sabino Ester Cerdeira 
Published: April 2020

Abstract
Erythrovirus are now classified in three groups: genotype 1 (prototype Pvbaua); genotype 2 (Lali prototype) and genotype 3 (V9 prototype). The role of genotypes 2 and 3 in the development of disease remains uncertain. We have recently showed that those genotypes may represent 50% of the infections in Brazil. The objective of this study is to verify if these viruses are associated with cytopenia of unknown origin. We have designed a case control study in which the prevalence of erythrovirus in the bone marrow sample was compared among cases of cytopenia of unknown origin and 2 controls: bone marrow donors (C1) and, individuals with chronic leukemia (C2). For detection of the virus a nested PCR was performed in bone marrow and plasma samples. Table 1 describes the results obtained in 68 C0, 35 C1 and 67 C2 collected during the year of 2007. The prevalence of the virus in bone marrow was the same in the 3 groups. This result suggests that erythrovirus are common in bone marrow and probably not are responsible for most of cytopenias of unknown origin. A detection of this agent only in bone marrow has little clinical relevance.
Table 1. Results obtained during the year of 2007
Cases (C0) Cytopenias Control 1 (C1) Bone marrow donors Controle 2 (C2) Chronics Leukemias Bone marrow Plasma Bone marrow Plasma Bone marrow Plasma positive total positive total positive total positive total positive total positive total 6 (9%) 68 1 (1%) 68 3 (8%) 35 0 35 5 (7%) 67 0 67
Effect of the Absolute Lymphocyte Count on Induction Chemotherapy Outcomes in Adult Patients with Acute Leukemia
Authors: Daily Karen C , Hsu Jack W , Subbiah Sukanthini , Aman Shazia , Hou Wei , Wingard John R 
Published: April 2020

Abstract
Abstract 4853 was withdrawn on April 3, 2009 by authors' request.
Molecular Events of T-Cell Lymphoblastic Leukemia in Early Childhood
Authors: Mansur Marcela Braga , Emerenciano Mariana , Brewer Lilian , Candian Kátia Cristina da Cruz Machado , Pombo-de-Oliveira Maria S. 
Published: April 2020

Abstract
T-cell acute lymphoblastic leukemia (T-ALL) predominantly in children &gt; 5 years-old, which accounts for approximately 15% of pediatric ALL in age range. Recent studies demonstrated that an accumulation of chromosomal rearrangements and other genetic anomalies is necessary for T-ALL development. However causal factors and time latency for childhood T-ALL remains enigmatic. Unlike B-cell precursor ALL that involves genetic events prenatally or in early infancy, T-ALL early childhood have controversial results regarding prenatal origin. Therefore, we conducted a molecular screening in infants with T-ALL searching for the most common genetic markers associated with this malignancy. This series of cases was selected from the incident cases included in the Brazilian Collaborative Study for IAL. The diagnosis of T-ALL was made according to morphology and EGIL classification, followed by conventional karyotyping. Sixteen cases of T-ALL IL were analyzed either by PCR-RFLP (FLT3), RT-PCR (MLL, SIL/TAL1 and HOX11L2) or PCR-DHPLC (NOTCH1), tracing the genetic alterations commonly found in these genes. Mean age at diagnosis was 14.6 months (6–24), there was a predominance of high white blood cells (WBC) count, and a poor survival in this series of cases. Cytogenetic aberrations included del(12p) (#2), t(11;14) (#3), del(6)(q23) and del(7) (q32) (#11), and 49, XY,+6,+8,+19 (#15). Details of all molecular markers are presented in Table. Then molecular markers were identified in 8 out of 16 (50%) T-ALL cases. The observed markers included MLL rearrangements (n=2), FLT3-ITD (n=1), SIL/TAL1 (n=2), HOX11L2 (n=1), and NOTCH1 (n=4). SIL/TAL1 and NOTCH1 abnormalities were found concomitantly in one case (#7) in the diagnostic sample. By the fact that the onset of T-ALL arose in a short time latency from birth to diagnosis we suggested that T-ALL might originate prenatally in these cases.
Table. Laboratorial and Molecular Features of Patients
ID Age(months) Gender WBC(×109/L) EGIL MLL FLT3 SIL/TAL1 HOX11L2 NOTCH1 Outcome #1 24 F 86.0 T-I Neg WT Neg Neg WT Dead #2 20 F 240.1 T-I Neg WT Neg Neg WT Dead #3 22 M 380.1 T-II Neg ITD Pos Neg WT Dead #4 24 M 440.1 T-IV Neg WT Neg Neg WT Dead #5 20 F 330.0 T-IV Pos1 WT Neg Neg WT Alive #6 12 M 80.1 T-IV Neg WT Neg Neg WT Dead #7 13 F 71.3 T-I Neg WT Pos Neg Mut Lost #8 9 M 56.2 T-IV Neg WT Neg Neg Mut Alive #9 14 M 57.1 T-IV Neg WT Pos Neg WT Lost #10 7 M 110.0 T-IV Pos2 WT Neg Neg WT Alive #11 17 M 180.1 T-I Neg WT Neg Neg WT Alive #12 20 F 78.6 T-I Neg WT Neg Neg WT Dead #13 9 M 71.0 T-IV Neg WT Neg Neg WT Dead #14 9 F 50.0 NA Neg WT Neg Neg Mut Dead #15 8 M 154.0 T-IV Neg WT Neg Neg Mut Alive #16 6 F 131.6 T-IV Neg WT Neg Pos WT Alive
Abbreviations: F, female; M, male; WBC, white blood cells count; NA, not available; Neg, negative; Pos, positive; WT, wild-type; ITD, internal tandem duplication; Mut, mutated; 1MLL/AF4; 2MLL/ENL.