bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of a Smartphone-Based Health Coaching Intervention for Patient Self-Management of Nutrition in the Post-Chemotherapy Setting
Authors: Chen Connie E , Mao Alice Y , Murray Jontrice G , Oran Betul , Qazilbash Muzaffar H. , Shah Nina , Ahmed Sairah , Bashir Qaiser , Hosing Chitra , Shpall Elizabeth J. , Steele Joseph R , Champlin Richard E. , Parmar Simrit 
Published: October 2019

Abstract
Introduction. While quality of life (QoL) has become an increasingly important outcome measure following hematopoietic stem cell transplant (HSCT), ongoing support services available to patients post-HSCT patients are limited due to high cost and limited reimbursement. Smartphone devices offer a novel means by which to offer low cost, longitudinal support through the use of virtual health coaches. However there is little existing research on the acceptability and effectiveness of using smartphones to deliver health coaching for patients with malignant diseases after HSCT.
Methods. Patients were recruited in the outpatient setting in the stem cell transplant clinic at MD Anderson Cancer Center to enroll in digital health coaching. Upon enrollment, patients were asked to download a smartphone application (Vida Health), which allowed participants to communicate in real time with a health coach through live video, phone, or text messages. Coaches provided health education, offered ongoing encouragement, and helped patients set small weekly goals to enhance nutrition, physical activity, stress management, and medication adherence. Patients completed the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) survey at baseline and 3-month follow up.
Results. A total of 62 patients completed at least 3 months of Vida health coaching. The median age was 56 years (45-72 years) and 41% were women. Time elapsed since HSCT ranged from 3 months to 9 months with primary diagnoses being: Myeloma 50%, Lymphoma 20%, Other Hematologic Malignancy 30%. Primary goals as stated by patients were: 72% optimizing nutrition, 60% stress management and emotional support, 60% remembering to take medications, 45% improving sleep, 20% staying physically active. 68% of patients sent at least one message to coach with an average 29 messages sent from patient to coach during the 3 month coaching period. FACT-BMT scores improved significantly after coaching with a 27% improvement in physical wellbeing (pre-coaching mean 6.1, post-coaching 4.7) and a 53% improvement in functional wellbeing (pre-coaching mean 13.8, post-coaching 21.1). Emotional wellbeing also increased 40% (from mean of 10.3 to 6.2).
Conclusion. These preliminary findings suggest digital health coaching may help post-HSCT patients improve QoL, particularly among physical, functional, and emotional domains. We believe that utilizing novel tools such as smartphone-enabled health coaching may offer an important means by which to continue to support patients' wellbeing outside of the clinic.

Disclosures
Chen: Vida Health: Employment, Equity Ownership. Mao:Vida Health: Employment.
Better Transplant Outcomes with Umbilical Cord Stem Cells in Patients with Dyskeratosis Congenita
Authors: Gupta Ashish O. , Shein Steven L , Dalal Jignesh D 
Published: October 2019

Abstract
Background:Dyskeratosis congenita (DKC) is a rare genetic bone marrow failure (BMF) syndrome of unknown etiology with a multisystem involvement and predisposition for cancer. It presents as a classic triad of dystrophic nails, oral leukoplakia and skin hyperpigmentation. Hematopoietic stem cell transplant (HSCT) has been tried as a treatment option but there is limited data on outcomes in these patients.
Methods:As the disease is rare with high mortality, there have been no prospective studies. Retrospective database analysis is an effective means to evaluate outcomes in this patient population. Our study utilized Pediatric Health Information Systems (PHIS) database, which is an administrative quality-controlled database from 43 not-for-profit children's hospital, to analyze healthcare outcomes in pediatric patients with DKC. ICD-9 code 757.39 was used to identify the disease classification and as the only condition with an indication for stem cell transplant, we isolated the cases that underwent HSCT with that diagnostic code.
Results: A total of 40 patients with DKC were identified who underwent transplant. A higher incidence was noted in Caucasian males with no significant difference in mortality across gender and ethnicity. The median length of hospitalization was 48 days (range 8.5 to 160.5 days) with a mean age of hospital admission at 93 months (95% CI: 70, 117). All the transplants were allogeneic with almost 20% umbilical cord (UCT) stem cell transplants. There was 15% mortality noted in this patient population, with all of deaths occurring prior to 2012. The complication rate (including acute and chronic GVHD as well as graft failure) was noted to be 37.5%, with acute GVHD being most common (20%). Fludarabine, Alemtuzumab, Cyclophosphamide, and Melphalan based conditioning regimen were most commonly used. Cyclosporine (65%), steroids (80%), Mycophenolate mofetil (50%) and Tacrolimus (40%) were commonly used for GVHD prophylaxis. Despite small numbers, significantly lower mortality was noted in UCT as compared to the other allogeneic stem cell transplants (p<0.01).
Conclusion: Limited literature is available on pediatric transplant outcome data in DKC. UCT has better transplant outcomes in DKC patients due to longer telomere lengths of donor stem cells. Larger studies are needed for to compare transplant outcomes from different sources.

Disclosures
No relevant conflicts of interest to declare.
Erythroferrone Regulates Hepcidin Expression Independently of Matriptase 2
Authors: Kautz Leon , Aschemeyer Sharraya , Gabayan Victoria , Ganz Tomas , Nemeth Elizabeta 
Published: October 2019

Abstract
Introduction: The iron-regulatory hormone hepcidin regulates the body iron stores and its expression is repressed when erythropoietic activity intensifies to meet the iron requirements for erythropoiesis (e.g. during anemia). Under the influence of erythropoietin (EPO), the hormone erythroferrone (ERFE) is secreted by erythroid precursors in the bone marrow and the spleen, and suppresses hepcidin synthesis to facilitate the recovery from anemia. However, the mechanism by which ERFE suppresses hepcidin is unknown. In contrast with forms of anemia in which hepcidin is suppressed, patients with mutations in transmembrane serine protease 6 (TMPRSS6) have iron-refractory iron deficiency anemia (IRIDA) but increased hepcidin production despite a severe anemia and elevated EPO levels. Recently, it has been suggested that matriptase-2 activity facilitates ERFE-mediated suppression of hepcidin. We therefore investigated the potential crosstalk between ERFE and Matriptase 2.
Methods: We first measured serum ERFE concentration in Tmprss6-/- mice. To assess the contribution of ERFE to the phenotype of Tmprss6-/-mice, we next generated Tmprss6-/-mice with disrupted Erfe (Erfe+/- Tmprss6-/-; Erfe-/- Tmprss6-/- and Erfe+/+ Tmprss6-/-). To determine whether ERFE requires TMPRSS6 to regulate hepcidin production, we treated freshly isolated hepatocytes from wild-type (WT) or Tmprss6-/- mice with conditioned medium from cells expressing recombinant ERFE or not.
Results: While wild-type mice have undetectable plasma ERFE (below the 500 pg/ml limit of detection), plasma ERFE concentration was elevated in Tmprss6-/- to levels comparable to those of WT animals 24 hours after phlebotomy (~3 ng/ml) but was lower than ERFE levels in thalassemic mice (~10 ng/ml). Ablation of Erfe in Tmprss6-/- mice did not result in any change in hematological parameters, hepcidin expression and iron levels compared to Tmprss6-/- animals at 6 weeks of age. However, treatment of WT and Tmprss6-/-hepatocytes with ERFE resulted in a comparable suppression of hepcidin mRNA expression.
Conclusion: Although matriptase-2 may dampen the BMP signaling under the influence of EPO, it is not part of the ERFE signaling pathway.

Disclosures
Ganz: Intrinsic Lifesciences: Other: shareholder and scientific advisor; Merganser Biotech: Other: shareholder and scientific advisor; Silarus therapeutics: Other: shareholder and scientific advisor; Keryx Biopharmaceuticals: Consultancy. Nemeth:Intrinsic Lifesciences: Other: shareholder and scientific advisor; Merganser Biotech: Other: shareholder and scientific advisor; Silarus therapeutics: Other: shareholder and scientific advisor.
Differentiating Thrombotic Microangiopathies Based on Laboratory Tests Other Than ADAMTS13 Using Machine Learning Technology
Authors: Koh Youngil , Lee SuYeon , Yun Hong-Seok , Yoon Sung-Soo , Kim Inho , Kim Byung-Su , Oh Doyeun 
Published: October 2019

Abstract
Introduction: ADAMTS13 activity level is crucial for differentiating thrombotic microangiopathies. However, ADAMTS13 testing is not readily available at site in many parts of the world. Hence, we developed an innovative algorithm that allow differentiation of thrombotic thrombocytopenic purpura (TTP) from other TMA's based on laboratory results other than ADAMTS13 using machine learning.
Methods: Two hundred- eight adult patients with either TTP (N=64) or TMA other than TTP (N=144) (ADAMTS13 cutoff level of 10%) were classified using three machine learning techniques (decision tree, random forest, and neural network), using a set of easily measured 19 clinical variables such as fever, Hb, ALT and so on. Basically, each clinical variable is not correlated with TTP (Absolute values of correlation coefficients are lower than 0.5), so we applied machine learning algorithms. First, we divided patient data into three parts, train, test and validation set. And then, we applied these 3 machine learning techniques, decision tree, random forest and neural network. Principal component analysis was also performed.
Results: As a single variable, platelet count, BUN and total bilirubin were the most important three variables that are predictive of differentiating TTP from other TMA's with accuracy of 82%. Random forest method increased accuracy to 85% and precision, and recall statistic is 0.828, and 0.832, respectively. Neural network did not do better without optimization than random forest method.
Conclusion: Machine learning technology seems promising in differentiating TTP from other TMA's if ADAMTS13 value is not available. These algorithms could support the physician in tailoring the management of TMA.
Correlation coefficient in our study Correlation coefficient in our study Scheme of Random Forest method used in our study Scheme of Random Forest method used in our study

Disclosures
Lee: SamsungSDS: Employment. Yun:Samsung SDS: Employment.
The Transcription Factor PU.1 Controls a Reversible Differentiation Program in Acute Myeloid Leukemia
Authors: McKenzie Mark D , Ghisi Margherita , Cimmino Luisa , Erlichster Michael , Oxley Ethan P , Liu Cynthia , Witkowski Matthew T , Liu Grace , Dakic Aleksandar , Simankowicz Emilia , DiRago Ladina , Metcalf Donald , Nutt Stephen L , Wall Meaghan , Ritchie Matthew E , Zuber Johannes , Dickins Ross A 
Published: October 2019

Abstract
Background: Acute myeloid leukemia (AML) is an aggressive malignancy characterized by clonal expansion of transformed myeloid precursors that fail to differentiate into mature cells. Since myeloid lineage maturation curbs self-renewal and is considered irreversible, engaging this process in AML is an attractive therapeutic strategy.
Results: Normal myeloid differentiation requires the transcription factor PU.1 (SPI1), which is functionally compromised in several AML subtypes and is directly inhibited by the recurrent fusion oncoproteins AML1-ETO and PML-RARA. To examine the importance of PU.1 suppression in AML maintenance in vivo, we have combined RNAi-mediated PU.1 inhibition with p53 deficiency to drive highly aggressive AML in mice. Using these models we find that restoring endogenous PU.1 activity in established AML in vivo is sufficient to trigger robust transcriptional, immunophenotypic, and morphological differentiation of leukemic blasts, yielding polymorphonuclear, neutrophil-like cells. Maturation of AML is associated with significant loss of cell viability and yields sustained disease clearance in vivo. Although PU.1 restoration is potently anti-leukemic, remarkably we find that subsequent suppression of PU.1 in mature neutrophil-like cells reverts them to a transformed state within several days. While mature AML-derived cells are slower to form blast colonies in methylcellulose cultures, their clonogenic frequency is only reduced four-fold relative to AML blasts suggesting highly efficient de-differentiation.
Conclusions: These results demonstrate that triggering myeloid differentiation can effectively resolve a p53-deficient model of treatment resistant AML, but also identify a previously unrecognised ability of AML cells to bidirectionally transition between transformed and differentiated states based on the activity of a single transcription factor. Our findings challenge the concept of 'terminal differentiation' in AML and highlight the importance of therapeutically eradicating leukemia cells at all stages of myeloid lineage maturation.

Disclosures
No relevant conflicts of interest to declare.
Blood Transfusion in Adult Patients with Sickle Cell Disease: Incidence of Alloimmunization
Authors: Master Samip , Ong Menchu , Mansour Richard Preston 
Published: October 2019

Abstract
Background:
Chronic red blood cell transfusion has been proven to be effective in prevention of strokes, silent cerebral infarcts, acute chest syndrome, recurrent priapism and in pregnancy. The use of regular transfusions to mitigate other morbidities of sickle cell disease (SCD) is evolving. In the silent infarct transfusion (SIT) trial in children, chronic transfusion lead to a significant improvement in quality of life. Some of the common reasons patient with SCD do not get chronic transfusion is fear of alloimmunization, iron over load and risk of viral infections. We did a retrospective analysis of adult patients with SCD who need chronic blood transfusion to determine the incidence of alloimmunization. At our institute all pediatric sickle cell patients needing chronic transfusion are placed on protocol, receive C, E, and K matched blood, and remain on the protocol until they become adults.
Methods:
We electronically collected data from 180 adult SCD patients who need chronic transfusions and analyzed the data for the number of transfusions received, incidence of allo- immunization and most common antibodies identified.
Results:
A total of 3967 red blood cell transfusions were administered on 180 adult sickle cell disease patients. Twenty five patients developed antibodies (13.8 %). Fifteen out of the 25 had multiple antibodies (60%). The alloantibodies identified were : anti- K(11), anti- E(12), anti- Fya(5), anti-C (4), anti-V (4), anti- S (3), anti-D (2), anti- Jkb (1), anti-Jsa(1) , and anti- Lutherana (3). Two patients had cold and 5 patients had warm autoantibodies.
Conclusion:
The policy to place patients with SCD needing chronic transfusion on protocol to receive C, E, and K matched red blood cells has decreased the alloimmunization rate to 13.8 %. We conclude that, fear of alloimmunization should not preclude physicians from using chronic red cell transfusions to prevent complications in sickle cell disease.

Disclosures
No relevant conflicts of interest to declare.
Prevalence of Chronic Hepatitis B, Hepatitis C and HIV in Adult Patients with Sickle Cell Disease
Authors: Master Samip , Patan Shajadi , Cingam Shashank , Mansour Richard Preston 
Published: October 2019

Abstract
Introduction:
Previous studies have shown that general prevalence rate of Hepatitis B is 0.3%, Hepatitis C is 1.3% and HIV is 0.39% in United States and that these infections are more common in low income groups and African Americans.
We did retrospective analysis of 458 adult patients with SCD to estimate the prevalence of these infections in our large population.
Methods: We retrospectively collected data of 458 adult patients with SCD to calculate prevalence of Hepatitis C, Hepatitis B and HIV. We also collected data of type of SCD and ethnicity.
Results: Out of total 458 adult patient with SCD, 25/458(5.4%) had Hepatitis C, 10/458(2.1%) had Hepatitis B and 4/458(0.87%) had HIV.
In SC type of SCD, prevalence of Hepatitis B was 1/114(0.87%), Hepatitis C was 4/114(3.5%) and HIV was 1/114(0.87%).
In SS type of SCD, prevalence of Hepatitis B was 7/263(2.66%), Hepatitis C was 19/263(7.22%) and HIV 3/263(1.14%).
In Sickle beta thal group, prevalence of Hepatitis B was 1/75(1.33%), Hepatitis C was 2/75(2.66%). No cases of HIV were fund in this group.
Conclusion:
The prevalence of HIV, hepatitis C and hepatitis B is higher in adult patient with SCD compared to general US population. At our institute we screen all patients with SCD for these infections, especially Hepatitis C and refer infected patients for the appropriate treatment.

Disclosures
No relevant conflicts of interest to declare.
Education, Employment, Social Support and Insurance Coverage in Adult Patients with Sickle Cell Disease
Authors: Master Samip , Arnold Connie , Davis Terry , Mansour Richard Preston 
Published: October 2019

Abstract
Introduction:
The average life expectancy of patients with sickle cell disease (SCD) has increased from early 20s well over 50 now. With improving pediatric healthcare, nearly all SCD patients become chronically ill adults, however little is known about these adult patients. This pilot study assessed adult SCD patients' age, education, literacy, employment, marital status, social support, and insurance status.
Methods:
A convenience sample of 100 sickle cell patients 18 and older cared for at academic medical system hematology clinic were enrolled in the study. A research assistant administered a structured interview which included demographic questions (insurance, education, employment, social support, marital status and persons taking care of them at home). PROMIS (Patient-Reported outcomes measurement information system) surveys assessed depression, anxiety and pain.Literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine (REALM-SF) and cognitive ability, using the Callahan 6-Item Screener.
Results: Patients ranged in age from 19 to 66 years (mean age - 33), 100% were African Americans, 52% females. Education was varied - over one third ( 37%) did not graduate from high school, 26% were high school graduates, 14% had some college, and 12% were college graduates. Literacy was extremely low. No patient read at or above a 9th grade level, 99% < 6th grade level and 1% 7th- 8th grade. Only 16% were employed; 45% were married; 31% lived alone and 63% live with family. Almost all patients (98%) had insurance - 61% had Medicaid, 25% Medicare and 12% private insurance. Mean score of 5.77 on Callahan cognitive screener indicating patients did not need to be screened further for cognitive ability.
Conclusion:
Adult SCD patients in our study had very low education, literacy and employment levels. Many patients had inadequate social support. Our findings indicate that despite the fact that almost all patients were insured and theoretically had access to care, they still needed literacy and culturally appropriate information and on- going support to be able to understand and use health information and services to make appropriate health decisions and properly care for themselves.

Disclosures
No relevant conflicts of interest to declare.
Genome-Scale Screen Reveals Genes Required for Lenalidomide-Mediated Degradation of Aiolos By CRL4-CRBN
Authors: Sievers Quinlan , Gasser Jessica , Cowley Glenn , Doench John G , Fischer Eric , Ebert Benjamin L 
Published: October 2019

Abstract
Lenalidomide exerts its therapeutic effects in the malignancy multiple myeloma by facilitating the degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) by the CRL4-CRBN E3 ubiquitin ligase. In the following study we utilized a positive selection, genome-scale CRISPR-Cas9 screen in the lenalidomide-sensitive myeloma cell line, MM1S, to further our understanding of the molecular machinery which regulates and is required for lenalidomide-mediated modulation of CRL4-CRBN. The gRNAs demonstrating the greatest enrichment following selection with lenalidomide belong to cereblon, the molecular target of lenalidomide and substrate receptor for the CRL4-CRBN ubiquitin ligase. Additionally, 20 of the top 30 genes highlighted by the screen are implicated in both the positive and negative regulation of cullin-ring ligases (CRLs), emphasizing both the importance of cereblon's E3 ligase function in mediating cell death as well as the equilibrium of forces required for proper function of CRLs. Among these genes were the ubiquitin-donor E2 enzymes UBE2D3 and UBE2G1; despite the relevance of E2s to E3 ligase biology it has been difficult to determine via traditional methods which of the ~35 E2 enzymes are utilized by a given E3 ligase. Here we demonstrate that G1 and D3 fulfill distinct functional roles and cooperate with the CRL4CRBN E3 ligase to ubiquitinate an aiolos reprorter with lysine-48 linkages. In aggregate these findings confirm the power of CRISPR-Cas9 positive selection screening to reveal drug mechanism-of-action and provides a paradigm for the identification and functional characterization of E2-E3 pairings.

Disclosures
Fischer: Novartis: Consultancy.