bluuebunny/crossref_metadata_2025_split huggingface dataset:
Martial Arts Intervention Decreases Pain Scores In Children With Malignancy
Authors: Cohen Cindy , McCrae Jocelyn , O'Malley Barbara , Goldberg Elimelech , Bluth Martin H 
Published: October 2019

Abstract

Background
Martial arts intervention in disease has been mostly limited to inflammatory, musculoskeletal or motor diseases (rheumatoid / osteoarthritis, fibromyalgia, Parkinson’s disease) where a mechanical intervention effects positive change. However, the application and benefit to malignancy is not well described.

Methods
Ninety four children with childhood malignancies enrolled in a martial arts program which encompassed both “soft” (meditation, chi gung) and “hard” (karate) martial arts platforms over the course of 12 months. Pain scores were recorded pre and post intervention. Data are reported as percent change from baseline pre intervention values compared with post using Wilcoxen Signed Ranks test comparing pain score means for all cases; with significance p< 0.05)

Results
The majority of participants were African American (>95%) with a M:F ratio of 3:1. Further, most participant scored improvement in pain after 1-3 encounters. Pain scores prior to intervention were recorded on a scale of 0-10. Patients who partook in the martial arts program demonstrated a reduction in pain scores of 14-30.2% (p<0.05) based on mean comparisons as a group or when corrected for number of visits. Differences in pain scores trended as more pronounced in older vs. younger children, but were not significant (p>0.05). Differences in gender were not significant (p>0.05).

Conclusion
Martial arts can provide a useful modality to decrease pain in childhood cancer. This can improve patient compliance with respect to medical and surgical management thus reducing disease morbidity and healthcare costs.

Disclosures:
No relevant conflicts of interest to declare.
Vitamin B12 Deficiency In Patients With Normal Blood Count
Authors: Al-Momen Abdul Kareem M , AL-Aqeel Abdullah A. , Student Medical , Aseeri Mohammed A. , Student Medical , Al-Fawaz Khaled A. , Student Medical , Al-Molhem Abdulaziz , Student Medical , Hasanato Rana M 
Published: October 2019

Abstract

Background
Vitamin B12 (Cobalamine) is essential for protein synthesis, cell proliferation and optimal systemic function, particularly for nervous system and blood. Moderate vitamin B12 deficiency is common even with normal hematological parameters. Diagnosis and treatment are delayed because of non-specific symptoms, normal blood count and lack of awareness.

Objectives
To find out the prevalence of hidden vitamin B12 deficiency in patients with normal blood count.

Materials and Methods
We reviewed the results of vitamin B12 tests which were ordered for patients at King Khalid University Hospital, King Saud University between 1st of January- 30thof December 2012. Those with low vitamin B12 and normal blood count were contacted and interviewed and were asked for consent to participate in this retrospective study and to answer detailed medical history questions on dietary habits, medical illnesses, gastro-intestinal surgical procedures, and long term medications.

Results
Out of 3045 patients, there were 415 (155 males and 260 females, aged 36 +/- 18 years) with normal blood count, but low vitamin B12 level, which was between 40-140 pmol/l ( normal 145-637). 350 patients agreed (81 males and 170 females), but complete information was obtained only from 251 patients (71.71%). Symptoms included fatigue, tingling and numbness, impaired short-term memory, insomnia and impaired concentration. Identified causes of Vitamin B12 deficiency were as follows: 65 patients (26%) had partial gastrectomy, 12 (5%) had resection of the terminal ileum, 16 (6%) had gastric atrophy, 18 (7%) had celiac disease, 36 (14%) were vegetarians, 49 (20%) were diabetic on metformin, 47 (19%) were on proton pump inhibitors, and in 8 (3%) the cause could not be identified.

Conclusion
Vitamin B12 deficiency is common even in patients with normal hematological values. There is a need for continuous awareness program for physicians, dietitians, and general population to identify risk factors, and to implement guidelines for prevention, early detection and treatment of hidden Vitamin B12 deficiency.

Disclosures:
No relevant conflicts of interest to declare.
Hospitalization Outcome Metrics Based On Payer Status In Myeloma Patients That Receive Autologous Stem Cell Transplant (ASCT)
Authors: Gowda Sachit , Langston Amelia , Kaufman Jonathan L. , Shah Nishi N , Lechowicz Mary Jo , Boise Lawrence H. , Lonial Sagar , Nooka Ajay K. 
Published: October 2019

Abstract

Background
Myeloma patients have experienced great survival benefits in the last decade due to the use of novel agents and autologous stem cell transplant (ASCT). Prior studies report a complex interplay between payer status and the receipt of ASCT. We have evaluated if the payer status affects outcome metrics of length of stay (LOS), in-hospital mortality rate (IHM), and total hospitalization charges in the context of survival benefit of myeloma with this procedure.

Methods
We used the NIS (Nationwide Inpatient Sample) 2001-2010 database (part of the HCUP database) to obtain the patient data. Using private insurance as the reference group, we performed multivariate logistic regression to understand the association of payer status with LOS, IHM, hospitalization charges. We adjusted our model for age, race and the presence or absence of co-morbidities. Comorbidites were identified using comorbidity software that created measures reported by Elixhauser et al.

Results
From 01/2001 until 12/2010, 25656 admissions for ASCT as principal procedure for the principal diagnosis of multiple myeloma were included in our analysis. The IHM rate during this period based on payer status was 3.04%, 1.56%, 1.20% and 0.4% for medicare, medicaid, private insurance and others, respectively. Median LOS for medicaid and medicare were 17 days while private insurance and other insurances had a median LOS of 16 days. Medicare patients undergoing ASCT had higher likelihood of IHM compared to private insurance [Odds ratio: 2.62 ( 95%CI 1.46 – 4.72)]; while medicaid patients had non-significant increase. LOS in medicaid patients was longer compared to private insurance [(Odds ratio: 1.53 ( 95%CI 1.16-2.02)].

Conclusion
Myeloma patients with medicare undergoing ASCT had higher likelihood of in-hospital death compared to patients with private insurance. Medicaid patients had a lengthier in-hospital stay but there seems to be no significant difference in hospitalization charges in the different payer groups. However, the acceptable overall cumulative mortality rate suggests that myeloma patients can continue to enjoy the survival benefits associated with ASCT despite payer status. Further studies evaluating long-term outcomes outside the hospital admission would be required to better understand the association of payer status with overall survival benefits of ASCT.

Disclosures:
Kaufman: Onyx: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Millenium: Consultancy; Merck: Research Funding. Boise:Onyx: Consultancy. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Onyx: Consultancy.
Upfront Allogeneic-Stem Cell Transplantation for Patients with Non-Localized Untreated Peripheral T-Cell Lymphoma: An Intention-to-Treat Analysis from a Single Center
Authors: Loirat Marion , Chevalier Patrice , Leux Christophe , Moreau Anne , Bossard Céline , Guillaume Thierry , Gastinne Thomas , Delaunay Jacques , Blin Nicolas , Mahe Beatrice , Dubruille Viviane , Augel-Meunier Karine , Peterlin Pierre , Maisonneuve Herve , Morineau Nadine , Moreau Philippe , Jardel Henry , Mohty Mohamad , Moreau Philippe , Legouill Steven 
Published: October 2019

Abstract
Background. Peripheral T-cell lymphomas (PTCLs) are rare and heterogeneous diseases with dismal outcome when treated with chemotherapy alone. Because allogeneic stem cell transplantation (allo-SCT) can cure relapse-refractory patients, we hypothesised that upfront allo-SCT may be less toxic and provide a better outcome. Therefore, all patients that presented with advanced PTCL in our institution at diagnosis were scheduled to undergo upfront allo-SCT after induction chemotherapy.
Patients and methods. The aim of the present work was to assess the feasibility and toxicity of upfront allo-SCT. From 2004 to 2012, 49 newly diagnosed PTCL patients were scheduled to receive upfront allo-SCT. An HLA-matched donor was found for 42 patients: related to the patient in 15 cases, unrelated in 20 cases, and suitable cord blood units were used in seven cases.
Results. After induction chemotherapy, 17 patients reached complete remission and 29 (60%) proceeded to upfront allo-SCT. For all patients, the one and two-year overall survival (OS) rates were 59% (CI95%; 47-75) and 55 % (CI95%; 43-71), respectively. The most frequent reason we did not proceed to allo-SCT was disease progression or insufficient response after induction. For transplanted patients, the one- and two-year OS were 76% (CI95%; 62-93) and 72.5% (CI95%; 58-91), respectively. Toxicity related mortality one year after allo-SCT was only 8.2% (CI95%; 0-18.5). The two-year progression-free survival (PFS) rate of patients who did not proceed to allo-SCT (n= 20) was below 30%. The disease status at the time of transplantation was a strong predictive marker for both PFS and OS in transplant patients.
Conclusions. Upfront allo-SCT in PTCLs is feasible with low TRM, and it provides long-term disease control. However one third of patients remain chemo-refractory, and thus, new therapeutic approaches are warranted. The role of upfront allo-SCT compared to other therapeutic approaches in PTCLs requires investigation in randomized studies.

Disclosures
No relevant conflicts of interest to declare.
SEC23B Deficiency Results in Different Phenotypes in Humans and Mice
Authors: Khoriaty Rami , Vasievich Matthew , Jones Morgan , Chase Jennifer , Everett Lesley , Zhang Bin , Maillard Ivan , Ginsburg David 
Published: October 2019

Abstract
SEC23B mutations in humans result in the autosomal recessive disease Congenital Dyserythropoietic Anemia type-II (CDAII). CDAII is characterized by moderate anemia in increased bone marrow (BM) bi/multi-nucleated erythroblasts. Despite the identification of the genetic defect underlying CDAII, the pathophysiology of this disease remains unknown. SEC23A and SEC23B are paralogous components of the coat protein complex II (COPII)-coated vesicles, which transport secretory proteins from the Endoplasmic Reticulum to the Golgi apparatus. We generated SEC23B-deficient mice and demonstrated that these animals die perinatally exhibiting massive pancreatic degeneration (Tao et. al PNAS). To examine the impact of SEC23B-deficiency on adult murine hematopoiesis, we harvested fetal liver cells (FLC), which contain hematopoietic stem cells, from SEC23B-deficient or wild-type (WT) control E17.5 embryos and transplanted them into lethally irradiated C57BL/6J mice. Recipients of SEC23B-deficient FLC did not exhibit anemia or any other CDAII characteristic (Khoriaty et. al, Mol Cell Biol), and SEC23B deficient FLC competed effectively with WT FLC at reconstituting hematopoiesis when transplanted into lethally irradiated recipient mice (Khoriaty et. al, Mol Cell Biol). A Sec23bfl conditional-allele was also generated. Mice with hematopoietic-specific SEC23B-deficiency, generated by crossing Vav1-Cre into Sec23bfl mice, also exhibited normal hematopoiesis. In contrast, mice with pancreas-specific Sec23b deficiency generated by crossing the Sec23bfl allele to a p48-Cre or Pdx1-Cre resulted in a phenotype indistinguishable from complete SEC23B-deficiency, demonstrating that loss of pancreatic Sec23b expression is sufficient to explain the perinatal lethality of SEC23B-deficient mice. To investigate different phenotypes of SEC23B deficiency in humans and mice, the SEC23B/SEC23A expression ratio was examined in murine and human tissues. This ratio is higher in mouse pancreas (12.7) compared to BM (2.6), whereas it is higher in human BM (7.8) relative to pancreas (5.5). Taken together with the high degree of amino-acid identity between SEC23A and SEC23B (~85%), these data suggest that the tissue-specific functions of SEC23A and SEC23B have shifted during evolution between humans and mice. To determine if Sec23a can rescue the lethality of SEC23B-deficient mice, we have engineered Sec23a cDNA into the endogenous genomic locus of Sec23b (Sec23A-B) via recombinase-mediated cassette exchange. A heterozygous Sec23A-B intercross is in progress. Rescue of the SEC23B deficient phenotype by SEC23A protein expressed under control of Sec23b regulatory sequences would suggest that increasing the expression of either paralog in erythroid cells might be effective in the treatment of CDAII.

Disclosures
No relevant conflicts of interest to declare.
Single Cell Transcriptome-Based Dissection of Lineage Fate Decisions in Myelopoiesis
Authors: Olsson Andre , Grimes H. Leighton , Chaudhri Virendra K , Dexheimer Philip , Aronow Bruce J , Singh Harinder 
Published: October 2019

Abstract
In spite of tremendous advances in the analysis of hematopoietic progenitors and transcription factors that give rise to different lineages, molecular insight into the mechanisms that underlie cell fate choice at the level of individual cells is lacking. We utilized single-cell RNA sequencing of murine granulocyte-monocyte progenitors (GMPs) to analyze the molecular basis of cell fate choice. Over 200 libraries were generated with average read depths of 4 million per library and an expressed gene call of over 3,800 genes with FPKM >3. Our data reveal a varied but coherent spectrum of gene expression patterns in individual murine GMPs. The majority of cells could be clustered into ones expressing either granulocytic or monocytic genes, suggesting that they were primed for lineage determination. A minority of GMPs expressed a mixed-lineage pattern of genes. The single-cell data suggested an antagonistic transcription factor circuit involving Gfi1 and IRF8 that was validated with both loss- and gain-of-function experiments in GMPs. Our data highlight the utility of single cell RNA-Seq analysis to reveal molecular mechanisms controlling lineage fate decisions in hematopoiesis.

Disclosures
No relevant conflicts of interest to declare.
IL-21-Mediated Generation of Human Regulatory B Cells Occurs Independently of CD40 Signaling
Authors: Jahrsdörfer Bernd , Kaltenmeier Christof , Gawanbacht Ali , Beyer Thamara , Schütz Catharina , Hönig Manfred , Kirchhoff Frank , Schrezenmeier Hubert 
Published: October 2019

Abstract
Recently, we and others found that B cells differentiate into regulatory B cells (Breg) in response to interleukin (IL-)21. Of note, the key characteristic of human IL-21-induced Breg is expression of the serine protease granzyme B (GrB), whereas murine Breg, which require both IL-21 and CD40 ligand (CD40L) for their induction, predominantly express the immunosuppressive cytokine IL-10. Using two different disease models and various immunological methods, we further characterized the conditions leading to Breg differentiation in humans. Here, we demonstrate that in humans CD40L determines whether IL-21 induces differentiation of B cells into plasma cells (CD40L presence) or into GrB+ Breg (CD40L absence), which can directly control T cell proliferation by GrB-dependent degradation of the T cell receptor z-chain. Furthermore, we show that GrB+ Breg are circulating at high frequencies in the peripheral blood of untreated, highly viremic HIV patients, but not in healthy subjects. Of note, HIV-infected CD4+ T cells express IL-21, but not CD40L, and induce a GrB+ regulatory phenotype in healthy third party B cells in vitro. Consequently, addition of CD40L multimers can compensate for this insufficient T helper cell function, resulting in increased plasma cell/Breg ratios. Moreover, we investigated a patient with a congenital defect of Nuclear-Factor-kappa-B-Essential-Modulator (NEMO), which is essential for normal CD40 signaling. Even in the presence of viral infections, when CD4+ T helper cells from such patients are highly activated with strong expression of IL-21, they are not able to establish sufficient antibody responses. Instead, we found this patient to almost exclusively harbor B cells with a regulatory phenotype including high basal levels of GrB. When untreated NEMO B cells were co-cultured with allogeneic T cells from a healthy third party donor, these T cells failed to proliferate and to survive in response to a 6-day stimulation with anti-CD3/CD28 antibodies, an effect not observed with B cells from healthy donors. Since NEMO B cells lack normal CD40 signaling, our findings unequivocally demonstrate that in contrast to murine Breg IL-21-dependent induction of human Breg can occur in a CD40-independent fashion.

Disclosures
No relevant conflicts of interest to declare.
NADPH Oxidase Mediates Antiphospholipid Antibody-Induced Endothelial Cell Activation
Authors: Wu Meifang , McCrae Keith R. 
Published: October 2019

Abstract
Introduction: Antiphospholipid Syndrome (APS) is characterized by thrombosis and/or recurrent fetal loss in the presence of persistently elevated antiphospholipid antibodies (APLA). The majority of pathologic APLA are directed against β2-glycoprotein I (β2GPI), an abundant plasma phospholipid binding protein. APLA/anti-β2GPI antibodies activate endothelial cells in a β2GPI-dependent manner, though the underlying mechanisms are not well defined.
Objective: To define the role of NOX1 in the generation of ROS and activation of endothelial cells by anti-β2GPI antibodies.
Methods: Endothelial cells were incubated with β2GPI and either control or affinity-purified anti-β2GPI antibodies in the absence or presence of diphenyleneiodonium (DPI), an NADPH oxidase (NOX) inhibitor. Generation of reactive oxygen species (ROS) in treated cells and conditioned medium were measured by using fluorescent dyes (CM-H2DCFDA and CellROX Deep Red) or luminescent substrate. NOX mRNA and protein expression were assessed using quantitative PCR and immunoblot. Endothelial cell activation was measured by increased expression of E-selectin.
Results: Incubation of endothelial cells with β2GPI and anti-β2GPI antibodies stimulated ROS generation in endothelial cells, as well as the release of ROS into conditioned medium. The expression of NOX1 mRNA and protein levels were significantly increased in endothelial cells exposed to anti-β2GPI antibodies, but not control IgG (Figure 1). The ability of β2GPI and anti-β2GPI antibodies to induce endothelial cell E-selectin mRNA expression was blocked by pretreatment of cells with DPI (Figure 2), suggesting that ROS is required for downstream events underlying endothelial cell activation.
Conclusions: Endothelial cells exposed to β2GPI and anti-β2GPI antibodies generate ROS, which is subsequently released into the conditioned medium. NOX1 appears to be essential for ROS generation. The impairment of endothelial cell activation by DPI suggests that NOX is also essential for endothelial cell activation by anti-β2GPI antibodies. We hypothesize that production of ROS by NOX plays a central role in APLA-induced endothelial dysfunction.
Acknowledgment: This work was supported by an ASH Bridge Grant
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Characterization of Patients with Glanzmann Thrombasthenia and Identification of 17 Novel Mutations
Authors: Sandrock-Lang Kirstin , Oldenburg Johannes , Wiegering Verena , Halimeh Susan , Santoso Sentot , Kurnik Karin , Fischer Lars , Tsakiris Dimitrios , Sigl-Kraetzig Michael , Brand Brigit , Kraetzer Katharina , Deeg Niklas , Busse Eileen , Barbara Zieger 
Published: October 2019

Abstract
Background: Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder. Platelets from patients with GT show quantitative and/or qualitative defects of the platelet membrane glycoprotein (GP) IIb/IIIa complex, also called integrin αIIbβ3. On activated platelets the αIIbβ3 binds von fibrinogen and Willebrand factor which leads to platelet spreading and formation of platelet-platelet protein bridges.
Patients: In this study, 18 patients with GT were investigated with molecular genetic analyses. The patients presented with bleeding symptoms such as epistaxis, mucocutaneous bleeding, haematomas, petechiae, gastrointestinal bleeding, and menorrhagia.
Methods and Results: As cause of GT in the patients homozygous or compound heterozygous mutations in ITGA2B or ITGB3 were identified through sequencing of genomic DNA. All exons including exon/intron boundaries of both genes were analyzed. In summary, 16 of 18 patients revealed 27 different mutations (ITGA2B: n = 17, ITGB3: n = 10). Of these mutations, 17 have not been published yet.
Conclusion: In 16 patients mutations in ITGA2B or ITGB3 were identified as cause of GT. A total of 27 mutations including 17 novel missense, nonsense, frameshift and splice site mutations were detected. None of these mutations were present more than once in unrelated patients. In addition, 2 patients were without molecular genetic findings in ITGA2B or ITGB3 that could explain the suspected diagnosis of GT. We hypothesize that these patients may harbour defects in a regulatory element affecting the transcription of these genes or there may exist other proteins important for the activation of the αIIbβ3 complex that could be affected.

Disclosures
No relevant conflicts of interest to declare.