bluuebunny/crossref_metadata_2025_split huggingface dataset:
Existing Warfarin Therapy in Long-Term Care Facilities Maybe Inadequate.
Authors: Motlagh Bahareh , Verhovsek Madeleine M. , Papaioannou Alexandra , Mark Crowther , Dolovich Lisa , Campbell Glenda , Kennedy Courtney , Emili Anna 
Published: April 2020

Abstract
Despite evidence-based guidelines derived from large clinical trials supporting the use of warfarin for stroke prophylaxis, studies in elderly patients have shown that oral anticoagulants are not used optimally. The risk associated with inappropriate use is compounded by the observation that the elderly are at enhanced risk of thromboembolic complications compared with younger atrial fibrillation patients. All patients with atrial fibrillation who do not have a contraindication to warfarin, and who meet inclusion criteria, should be treated with warfarin to achieve a target International Normalized Range (INR) of 2.5 (range 2.0–3.0). INR levels of 2.0–3.0 have been shown to be relatively safe and more efficacious than lower target INR values in all age groups including the elderly. Patients with INR values below this range remain at increased risk of thrombosis, while those with INR values above the given range are at increased risk of bleeding. The primary objective of this study was to determine the achieved intensity of warfarin therapy in a cohort of patients living at long-term care facility. In such facilities optimal anticoagulation should be achievable, since laboratory monitoring, dose adjustment, and compliance can be achieved. In this study, data were collected on physicians’ warfarin prescribing practices as well as INR levels of 108 residents in five long-term care facilities in the Hamilton-Wentworth area over a period of 12 months. In total, 3146 INR values, extending over 28,256 patient-days of monitoring, were analyzed. Indications for warfarin were atrial fibrillation, transient ischemic attack, pulmonary embolus, cardiac valve replacement, myocardial infarction, and deep vein thrombosis. In general, the warfarin dosage was not determined using an established dosing algorithm. Our findings revealed that LTC residents spent approximately 40 percent of the time with INR values below 2.0. We therefore conclude, that the overall quality of anticoagulant therapy in long-term care patients may be inadequate. Our observations suggest that organized dosing algorithms may be of benefit in such settings, however this hypothesis needs to be confirmed in prospective studies. For this purpose we plan to implement a warfarin dosing algorithm in order to determine whether the percentage of time spent within the therapeutic INR range can be improved.
Influence of Hemotransfusion on the Arterial Compliance in the Patients with Chronic Anemia.
Authors: Barshai Josef , Nemets Anatoly , Oren Shmuel , Isakoy Irena , Lugassy Gilles 
Published: April 2020

Abstract
Arterial compliance disturbances are frequently observed among patients with chronic anemia. Few non-invasive studies were performed to determine hemodynamic changes in anemic patient. In this work we studied parameters of large arteries (C1) and small arteries (C2) compliance before and after blood transfusion (one packed cells unit(400cc)) by CR 2000 Hypertension Diagnostics Inc/Pulse Wave (Minneapolis MN, USA). We included 20 patients with chronic transfusion dependent anemia. The median age was 74±6 years. Twelve patients had MDS, 1 CML, 2 myelofibrosis, 2 NHL, one CLL, one thalassemia, and one patient with anemia of chronic disease. Hemoglobin range before transfusion was 7.5–9.0 g/dl. 14 patients also suffered from arterial hypertension, 5 from diabetes mellitus and received oral treatment; eight patients were smokers. Large arterial compliance before hemotransfusion was 9.8±3.8 ml/mmHgx10, and 9.2±2.9 after hemotransfusion (p&lt;0.05). Small arterial compliance before and after blood transfusion were without significant changes (2.8±1.2 ml/mmHgx10 and 3.04±1.2 ml/mmHgx10 respectively). The decrease in C1 is explained by increased blood pressure. Systolic blood pressure rose from 135±17mmHg to 152±26mmHg (p&lt;0.05), and diastolic pressure rose from 65±8mmHg to 72±10mmHg(p&lt;0.05). In conclusion, hemotransfusion of one packed cells for patients with chronic anemia led to significant decrease in large artery compliance most probably due to increase in blood pressure and blood volume. Hemotransfusion increases the small artery compliance but not significantly.
Evaluation of a Non-Invasive Hematocrit Determination Device.
Authors: Berrebi Alain , Amir Orna , Weinstein Aharon , Herzenstein Olga , Dvir David , Monashkin Emanuel , Gabis Efi , Holland Paul 
Published: April 2020

Abstract
Background: Non-Invasive Hematocrit (Hct) measurement devices have many potential advantages in primary and secondary medical situations. Primarily, these devices prevent the pain, the potential transmission of infectious diseases, and the need for trained technicians. However, truly non-invasive techniques have not been proven to be accurate enough to eliminate the need for blood sampling. A new, non-invasive clinical device, the NBM-100, was tested for accuracy.
Aims: To examine the accuracy of Hct measurements obtained by a non-invasive clinical device as compared to values determined using venous samples.
Methods: Clinical trials using the NBM–100 device were conducted in a blood donation center (USA) and a hematology clinic (Israel). The device utilizes a finger sensor with Occlusion Red/Near-InfraRed spectroscopy (O-RNIRS) technology to non-invasively measure hemoglobin and Hct levels. Studies were carried out on a group of 304 subjects (155 Female, 149 Male), ages 18–96 (average age 54.9). All study volunteers were tested non-invasively with the NBM-100 device, and invasively, using a venous sample evaluated on a Cell-Dyn (Abbott) blood analyzer. At the blood bank center, the NBM-100 measurements were performed before donation and the venous blood sample was taken after donation. To neutralize the decrease in Hct occurring during blood donation, as described in published clinical trials, a value of 2.2% was added to the reference venous values obtained from the blood bank center.
Results: The venous Hct measurements ranged from 15 to 51%. The mean NBM-100 Hct (36%) was the same as the mean venous result. The standard deviation of the difference between the invasive and noninvasive Hct readings was found to be 3.34% and the bias was 0.40%. The mean absolute error (MAE) of their difference was 2.66%. The relative absolute error (RAE) was 7.9%. The operating staff at all centers found the NBM-100 easy to use and appreciated by subjects.
Conclusions: This study indicates the potential use of the NBM-100 device as a useful and accurate non-invasive method for measuring a wide range of Hct in both a hospital (e.g. surgery and blood transfusions) and ambulatory setting (e.g. blood banks). Good agreement was found between the non-invasive NBM-100 and the invasive Cell-Dyn Hct measurements. The non-invasive system was found to be environmentally- and user-friendly by operating staff.
Infections and ABO Blood Groups in Burn Patients.
Authors: Kowal-Vern Areta , Boral Leonard I. , Yogore Mariano G. , Patel Harita , Brown Susan 
Published: April 2020

Abstract
Background: Lack of isohemmaglutinins may predispose individuals to infection. The purpose of this study was to determine if there was a relationship between infections and burn patient blood groups.
Methods: This was a retrospective review of burn patient data on infections and ABO blood groups between March 1999-May 2004. Chi-square and Mann-Whitney U with one-way ANOVA statistical analyses were performed.
Results: There were 1615 burn admissions; 794 patients were typed for blood groups; 179 patients received blood transfusions. Of the study population, African-Americans constituted 59%, Hispanics 21%, Caucasians 16%, and others 4%. Although age (mean±se: 37±2 years), % TBSA (11±2%), and inhalation injury (15%) were similar in all groups, patients with B blood group had longer BICU stays compared to the O blood group, p&lt;0.01. There was no statistically significant difference among the blood groups in the number of nosocomial wound infections, episodes of sepsis, bacteremia, urinary tract infections (UTIs) or pneumonia. The bacterial etiology was similar in all blood groups without any species preponderance. Transfused patients had a higher frequency of infections compared to those who were not transfused and significance was only reached in the comparison for UTIs, p=0.02.
Conclusions: Our data shows that burn patients with B and AB blood groups did not have an increased frequency of infections compared to the patients with A and O blood groups. Burn patients were immunosuppressed as part of their injury. Those who received transfusions probably had a further perturbation of their immune system, since blood products cause immunosuppression. Other factors such as inhalation injury and %TBSA also predisposed burn patients to infection. Transfusions rather than blood groups were associated with an increased number of nosocomial UTIs in burn patients.
Demographic Characteristics of the Burn Population by ABO Groups Blood Groups AB A B O mean ± s.e. Study Population # (%) 27 (3) 258 (32) 134 (17) 375 (47) Study African American (%) 4 29 21 46 Study Hispanic (%) 1 36 7 56 Study Caucasian (%) 3 37 14 46 BICU stay (days) 15±6 13±2 23±4 11±1 PRBC Transfusions (units) 7±2 9±2 13±3 8±1 UTI/Transfused # (%) 5 (100) 12 (92) 8 (89) 20 (60) UTI/Not Transfused # (%) 0 1 (8) 1 (11) 13 (40)
Umbilical Cord Blood Stem Cells Induced into Myeloid, Erythroid, or Megakaryocytic Pathways Are Susceptible to Infection by Porcine Endogenous Retroviruses (PERV).
Authors: Morgan Doris A. , Argaw Takele , Wilson Carolyn A. 
Published: April 2020

Abstract
Susceptibility of human hematopoietic stem cells to infection with porcine endogenous retroviruses (PERV) is of prime importance in determining the feasibility and safety of transplanting pig organs into humans. Under the influence of lineage specific cytokines, umbilical cord blood stem cells were evaluated for their permissiveness to PERV prior to linage commitment as well as after induction into the myeloid, erythroid or megakaryocytic pathways. CD34+ cells were plated in serum-containing nutrient medium supplemented with stem cell factor (SCF) to induce proliferation - a requirement for successful retroviral infection. Various microenvironment conditions included addition of lineage specific secondary cytokines for myeloid (G-CSF), erythroid (EPO), and megakaryocytic (TPO) commitment. After seven days, one-half of each culture was exposed to retroviral pseudotypes composed of replication competent wildtype PERV-NIH virions that also carry an MLV-based retroviral vector genome encoding β-galactosidase (β-gal) (Wilson et al, J. Vir,2000); control cultures were not exposed to the virus. Analyses for PERV infection were implemented after 72 hours’ viral exposure with the following observations: (1) exposure to PERV had no detected effect on proliferation nor on terminal differentiation of all three hematopoietic lineages; (2)PERV infected (β-gal +) cells (Fig.1) were detected in all cultures exposed to PERV regardless of microenvironment variations; and (3) PERV reverse transcription (DNA) and gene expression (RNA) as analyzed by PCR were positive only in virus exposed cultures (Fig. 2). Control cultures were negative in all analyses for PERV entry and expression. Preliminary observations indicate the erythroid lineage (SCF+E) may be more efficient in supporting PERV infection than the uninduced CD34+ cells (SCF) as well as those committed to the myeloid (SCF+G) and megakaryocytic (SCF+T) lineages. These results extend the initial observation that PERV could infect established hematopoietic cells lines to now show that the in vitro tropism of PERV also includes primary hematopoietic cells representing three lineages.
Fig. 1 Nuclear staining of PERV+ cells. Upper cell is in mitosis Fig. 1. Nuclear staining of PERV+ cells. Upper cell is in mitosis Fig. 2 qPCR Data of PERV-Exposed Cells Fig. 2. qPCR Data of PERV-Exposed Cells
Absence of nNOS Increases Longevity of Long Term Bone Marrow Cultures and Radiation Resistance.
Authors: Cao Shaonan , Greenberger Emily E. , Epperly Michael W. , Kanai Anthony J. , Greenberger Joel S. 
Published: April 2020

Abstract
Neuronal nitric oxide synthase (nNOS) has been shown to be localized to the mitochondrial membrane. The mitochondria play an important role in irradiation-induced apoptosis. Following irradiation, there is increased production of superoxide as well as an induction of nitric oxide in mitochondria. The combination of superoxide and nitric oxide results in production of peroxynitrite, a very strong oxidant that produces lipid peroxidation. Previous data have demonstrated that lack of nNOS protects the bladder from ionizing irradiation damage. To determine the role of nNOS in hematopoiesis, we established long term bone marrow cultures (LTBMCs) from nNOS deletion recombinant negative (knockout) mice as well as nNOS+/+ littermate mice. LTBMCs from nNOS knockout mice compared to +/+ control demonstrated increased total cumulative cell production (32.2 x 106 and 15.9 x 106 non-adherent cells, respectively), cobblestone island formation (5073 and 1106, respectively), and increased cumulative generation of day 14 CFU-GEMM colony forming cells per 105 plated (325 ± 30.4 and 9 ± 2.5 colonies, respectively) over 20 weeks in culture. IL-3 dependent non-adherent cell lines derived from the nNOS-/- and the nNOS+/+ cultures were tested for radiosensitivity. Cells from the nNOS−/− cell line demonstrated decreased radiation apoptosis 24 hours following irradiation, 5.89 ± 0.71% apoptotic cells compared to 10.42 ± 1.19% for the control littermates (p=0.041). Cell cycle analysis of littermate cells at 24 hours after 10 Gy demonstrated a G0/G1 and a G2/M block while there was no change in the cell cycle distribution of the nNOS−/− cells. The data demonstrate that absence of nNOS increases the longevity of hematopoiesis in LTBMCs and increases the radiation resistance of hematopoietic cell lines derived from such cultures.
BMI-1 Overexpression in 32Dcl3 Cells Suppresses Granulocytic Differentiation and Ameliorates Their Growth under IL-3 Diminished Conditions.
Authors: Hishida Asahi , Yamamoto Kazuhito , Sawa Masashi , Naoe Tomoki 
Published: April 2020

Abstract
The BMI-1 gene is one of the polycomb group (PcG) genes that have been shown to play essential roles in the self-renewal of both normal and leukemic stem cells. BMI-1 is reported to be highly expressed in primitive cells and its expression level decreases as bone marrow cells differentiate. We hypothesized that overexpression of BMI-1 might modulate the growth, differentiation and survival of 32D cells, and examined this hypothesis by generating BMI-1 overexpressing 32D cells. 32D cells were infected with MIG-BMI-1-IRES-EGFP vector or MIG vector, and the GFP positive rates of BMI-1 overexpressing 32D cells gradually increased under IL-3 diminished conditions, and the consecutive MTT assays using cells sorted by GFP positivity confirmed this finding, suggesting that BMI-1 could confer growth advantages on 32D cells under IL-3 diminished conditions.
Exposure of the GFP sorted 32D cells to G-CSF revealed that BMI-1 overexpression suppressed the granulocytic differentiation of 32D cells by G-CSF. The expressions of CD11b and Gr-1 were both suppressed by the overexpression of BMI-1, and real-time PCR analyses indicated that the expression levels of MPO was remarkably suppressed, while those of C/EBPα were not significantly changed.
Our experiments revealed that BMI-1 delayed granulocytic differentiation and ameliorated the growth of 32D cells under IL-3 diminished conditions.
Comparison of Stem Cells Harvested from Adipose Tissue and Bone Marrow.
Authors: Ogawa Rei , Fujimura Juri , Hanawa Hideki , Hirai Yukihiko , Kurai Toshiyuki , Mizuno Hiroshi , Hyakusoku Hiko , Shimada Takashi 
Published: April 2020

Abstract
Backgrounds: We have studied tissue engineering using both adipose-derived stem cells (ASCs) and bone marrow-derived stem cells (BSCs), and previously demonstrated that these stem cells differentiate into a variety of cell lineages both in vitro and in vivo.
Purposes: In this study, we investigated the biological differences between ASCs and BSCs harvested from mice. We studied the differences from the viewpoint of 1. morphology, 2. cell surface antigens, 3. proliferation potency, 4. pluripotency, and 5. gene transfer efficiency.
Methods: ASCs and BSCs were isolated from 5-week-old C57BL/6 mice. After subculture in a control medium, the cell surface markers expressed on the ASCs and BSCs were studied by flow cytometry. The cells were also incubated in osteogenic, chondrogenic and adipogenic media and differentiation was assessed by electron microscopy, special staining and RT-PCR. Gene transfer efficiency was studied using adenoviral, lentiviral, retroviral, adeno-associated viral (AAV) type 1, type 2, and type 5 vectors.
Results: BSCs were generally much more anaplastic than ASCs. However, ASCs and BSCs had generally similar properties as targets of viral vector mediated gene transfer, except that ASCs were particularly sensitive to lentiviral and oncoretroviral mediated gene transfer. The proliferation potency of ASCs was better than that of BSCs, but pluripotency and cell surface antigens were similar.
Conclusions: ASCs can be easily harvested and proliferated; ASCs may be better than BSCs for further experiments on stem cell biology and tissue engineering.
Differentiation of Human ES Cell into the Hemangioblast.
Authors: Carrier Ewa , Kausal Shermila , Srivastava Anand S. 
Published: April 2020

Abstract
We hypothesize that during early human embryo development a common endothelial/hematopoietic precursor is formed. This precursor, named the hemangioblast, is an early endothelial/hematopoietic precursor responsible for angiogenesis and both primitive and definite hematopoiesis. The aims of this work are 1) to establish the ES/EB model system for genotypic studies of early vasculo/hematopoiesis. 2) to phenotype human hemangioblast and establish standard culture/storage condition that will stabilize the phenotype of these cells for a defined period and permit consistent, predictable outcomes of experiments. Human ES (H-1 line) cells (NIH code WA01) has been maintained on g -irradiated MEF cells supplemented with DMEM/F12 media containing 4ng/ml b-FGF and 15% knockout serum by changing media everyday and passaging cells every 3–4 days. EBs were generated either in liquid or 1% methylcellulose cultures (1 x 104 ES cells per 35-mm Petri dish) in medium containing Iscove modified Dulbecco medium (IMDM), 15% FCS, 2 mM glutamine, 450 μM MTG, 50 μg/mL ascorbic acid, and 20% BIT (1% bovine serum albumin (BSA), 10 μg/mL insulin, and 200 μg/mL transferrin. In order to induce EB formation two days old hES cells were plated in 1% methyl cellulose in IMDM media supplemented with 50mg/ml ascorbic acid, 10mg/ml insulin, 200 mg/ml transferrin, 20% Bits, 15% FCS, 450mM MTG, 2mM-L-glutamine for 3days. To generate hemangioblasts, 1 x 104/mL EB cells were replated in 1% methylcellulose in the presence of IMDM, 10% PDS (bovine platelet-poor plasma-derived serum; Biomedical Technologies, Stoughton, MA), 2 mM glutamine, 450 μM MTG, 25 μg/mL ascorbic acid, 20% BIT, 5 ng/mL human vascular endothelial growth factor (hVEGF), 50 ng/mL SCF, 10 ng/mL human fibroblast growth factor 2 (hFGF-2), and 2 U/mL hEPO. RNA from day 0, 2, 3 and 4 days old EBs was collected for gene regulation studies. We have chosen to study the key regulatory genes (FLK-1, Runx-1, SCL, HEX, GATA-1) during this process. RNA collected from undifferentiated hES cells has been used as control. We observed expression of stemness genes: Sox-2 and Oct-4, in the undifferentiated ES cells while there was an upregulation in expression of Brachury on day 2 and FLK-1 and Hex genes in day 3 of differentiation. In hemangioblast forming cells (BL-CFC), we observed upregulation of FLK-1, SCL, Runx and downregulation of Brachury and Hex. This sptio-temporal expression profile of genes suggest that during hemangioblast formation and at the initial stages of differentiation hemangioblast fate is decided by Hex, while after day 2 the control is taken by FLk-1, SCl and Runx genes. Ongoing studies will define signaling pathways involved in this process. Understanding of molecular processes involved in hemangioblast formation will allow directed generation of this progenitor from human ES cells in the future.
HOVON 50/GMMG-HD3-Trial: Phase III Study on the Effect of Thalidomide Combined with High Dose Melphalan in Myeloma Patients up to 65 Years.
Authors: Goldschmidt Hartmut , Sonneveld Pieter , Breitkreuz Iris , van der Holt Bronno , Benner Axel , Barge Renee M.Y. , Salwender Hans , Bos Gerard M.J. , Glasmacher Axel , Raymakers Reinier , Scheid Christof , Huijgens Peter C. , Naumann Ralph , van Oers Marinus H.J. , Hänel Annette , Vellenga Edo , Martin Hans , Wijermans Pierre W. , Ho Anthony D. , Westveer Petra H.M. , Verhoef Gregor E.G. , Mazitschek Uta , Lokhorst Henk M. 
Published: April 2020

Abstract
The joint phase-III HOVON50/GMMG-HD3 trial was designed to assess the effect of thalidomide in induction treatment and as maintenance after high-dose therapy (HDT) and autologous stem cell transplantation (SCT) for multiple myeloma (MM). The standard treatment arm comprised 3 cycles of VAD, mobilisation with CAD+G-CSF (cyclophosphamide 1000 mg/m2, day 1; adriamycin 15 mg/m2, days 1–4; dexamethasone 40 mg, days 1–4; G-CSF until end of harvest), HDT with 1 or 2 cycles of melphalan 200 mg/m2, followed by autologous peripheral blood SCT (PBSCT), and maintenance with interferon-alpha (9 mio. U per week). In the experimental arm, TAD (thalidomide, 200 mg for HOVON / 400 mg for GMMG; adriamycin 9 mg/m2, days 1–4; dexamethasone 40 mg, days 1–4, 9–12, 17–21) was used for induction treatment. Mobilisation and HDT were identical to the standard arm. Experimental maintenance was thalidomide (50 mg per day). A first group of 406 patients (of 1050 included) are evaluable for the comparison of VAD vs. TAD and response after 1st HDT. A trend for a higher toxicity was observed in the TAD- compared with the VAD-arm (drop out: 15% vs. 8%, p= 0.10). Low molecular weight heparin was effective in the prevention of deep venous thrombosis during TAD-treatment (DVT-incidence 8% vs. 4% p= 0.15). The median number of stem cell collections to harvest at least one autograft was 1 in both arms (p= n.s.). Treatment-results are presented in table 1. In a subgroup of 90 GMMG-patients, 78% and 74% compared with 62% and 54% still received thalidomide compared with interferon-alpha at 12 and 24 months after start of maintenance. In summary, thalidomide+AD induce a significantly higher response rate, but this effect is completely offset by HDM. Therefore, results on EFS/PFS are necessary before thalidomide containing regimens can be defined as a standard for induction treatment before HDT. The maintenance treatment with thalidomide is better tolerated compared with interferon-alpha.
Treatment results (n=406) after VAD/TAD and after first HDT After VAD After TAD p-value PR 60% 73% &lt;0.001 CR 3% 7% 0.11 PR/CR 63% 80% 0.001 After VAD/HDT After TAD/HDT p-value PR 75% 72% 0.8 CR 13% 19% 0.3 PR/CR 88% 91% 0.4