bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive Control of an Artificial Pancreas Using Model Identification, Adaptive Postprandial Insulin Delivery, and Heart Rate and Accelerometry as Control Inputs
Authors: Resalat Navid , Hilts Wade , Youssef Joseph El , Tyler Nichole , Castle Jessica R. , Jacobs Peter G. 
Published: October 2019

Background: People with type 1 diabetes (T1D) have varying sensitivities to insulin and also varying responses to meals and exercise. We introduce a new adaptive run-to-run model predictive control (MPC) algorithm that can be used to help people with T1D better manage their glucose levels using an artificial pancreas (AP). The algorithm adapts to individuals’ different insulin sensitivities, glycemic response to meals, and adjustment during exercise as a continuous input during free-living conditions. Methods: A new insulin sensitivity adaptation (ISA) algorithm is presented that updates each patient’s insulin sensitivity during nonmeal periods to reduce the error between the actual glucose levels and the process model. We further demonstrate how an adaptive learning postprandial hypoglycemia prevention algorithm (ALPHA) presented in the previous work can complement the ISA algorithm, and the algorithm can adapt in several days. We further show that if physical activity is incorporated as a continuous input (heart rate and accelerometry), performance is improved. The contribution of this work is the description of the ISA algorithm and the evaluation of how ISA, ALPHA, and incorporation of exercise metrics as a continuous input can impact glycemic control. Results: Incorporating ALPHA, ISA, and physical activity into the MPC improved glycemic outcome measures. The adaptive learning postprandial hypoglycemia prevention algorithm combined with ISA significantly reduced time spent in hypoglycemia by 71.7% and the total number of rescue carbs by 67.8% to 0.37% events/day/patient. Insulin sensitivity adaptation significantly reduced model-actual mismatch by 12.2% compared to an AP without ISA. Incorporating physical activity as a continuous input modestly improved time in the range 70 to 180 mg/dL during high physical activity days from 84.4% to 84.9% and reduced the percentage time in hypoglycemia by 23.8% from 2.1% to 1.6%. Conclusion: Adapting postprandial insulin delivery, insulin sensitivity, and adapting to physical exercise in an MPC-based AP systems can improve glycemic outcomes.
Patient-Reported Outcome Measures and Provocative Testing in the Workup of Empty Nose Syndrome—Advances in Diagnosis: A Systematic Review
Authors: Gill Amarbir S. , Said Mena , Tollefson Travis T. , Strong E. Bradley , Nayak Jayakar V. , Steele Toby O. 
Published: October 2019

Background The last 5 years have seen a surge of both clinical and scientific interest in empty nose syndrome (ENS). Although ENS is still considered a controversial diagnosis plagued by a lack of standardized diagnostic criteria, ENS is increasingly becoming recognized as a legitimate, physiologic disease entity. As such, it is important for clinicians to understand the most up-to-date diagnostic tools to assess ENS, confirm the diagnosis, and create a more standardized means to counsel these complex patients. Objective Contemporary literature review to discuss diagnostic modalities in the evaluation of ENS, in order to introduce evidence-based diagnostic criteria. Methods A systematic review was conducted in PubMed and Embase (2013–2019) using the search term “empty nose syndrome” to identify peer-reviewed articles on the topic of ENS. Articles advancing contemporary methods of ENS diagnosis and testing were included. A quality assessment was conducted using The Rational Clinical Examination Levels of Evidence. Results The novel development of the Empty Nose Syndrome 6 Questionnaire (ENS6Q) offers the clinician a validated patient-reported outcome measure to supplement history and physical examination. The in-office cotton test, performed by placing an endoscopically directed cotton plug in the site of tissue loss, may help to identify patients who may benefit from turbinate augmentation. Tools such as the sinus computed tomography scan, computational fluid dynamics, and intranasal trigeminal nerve function testing currently have insufficient evidence to support routine use in the workup of ENS. Up to 66% of ENS patients present with comorbid anxiety or depression. Conclusion The ENS6Q and cotton test assist in creating a standardized approach to the evaluation of patients suspected of ENS. These instruments should be used as an adjunct, rather than the sole criteria, on which to ascertain the presumptive diagnosis. Patients suspected of ENS should be screened for comorbid psychological dysfunction.
Endoscopic measurement of gastric pH is associated with persistent acid reflux in patients treated with proton pump inhibitors for gastroesophageal reflux disease
Authors: Januszewicz Wladyslaw , Hartley James , Waldock William , Roberts Geoffrey , Alias Bincy , Hobson Anthony , Wernisch Lorenz , di Pietro Massimiliano 
Published: October 2019

BackgroundAlthough proton pump inhibitors are the mainstay of gastroesophageal reflux disease treatment, up to 30% of patients have a poor symptomatic response. Ambulatory pH impedance monitoring is the gold standard to assess whether this is due to persistent acid reflux. We aimed to characterize clinical predictors of persistent esophageal acid reflux on proton pump inhibitors including gastric pH measured during endoscopy.MethodsWe prospectively recruited patients with gastroesophageal reflux disease and/or Barrett esophagus on proton pump inhibitors. All patients completed a symptom questionnaire and underwent gastroscopy with gastric pH analysis, immediately followed by ambulatory 24‐hour pH impedance. We used a modified cutoff of 1.3% for pathological esophageal acid exposure time. A multiple linear regression model was used to analyze the correlation between acid exposure time and predictive variables.ResultsWe recruited 122 patients, of whom 92 (75.4%) were included in the final analysis (44 male (47.8%), median age 53 years (interquartile range (IQR): 43–66)). Forty‐four patients (47.8%) had persistent acid reflux with a median total acid exposure time of 2.2% (IQR: 1.2–5.0), compared with 0.1% (IQR: 0.0–0.2) in patients without persistent reflux (n = 48; p < .001). There was no difference in age, sex, body mass index, proton pump inhibitor regimen, diagnosis of hiatus hernia or Barrett esophagus, and severity of symptoms between patients with normal and abnormal acid exposure time. Median gastric pH was significantly lower in patients with persistent acid reflux (5.8 vs 6.6, p = .032) and it correlated with the total acid exposure time (p = .045; R2 = 12.0%). With a pH cutoff of 5.05, single‐point endoscopic gastric pH analysis had an area under the receiver operating characteristic curve of 63.0% (95% confidence interval: 51.3–74.7) for prediction of persistent acid reflux.ConclusionsSymptoms and clinical characteristics are not useful to predict persistent acid reflux in patients on proton pump inhibitors. One‐point gastric pH correlates with 24‐hour esophageal acid exposure time and could guide clinicians to assess treatment response; however, its utility needs validation in larger studies.
Diagnostic Accuracy of Transvaginal Sonography in the Detection of Endometrial Polyps
Authors: Poliakova Yevheniia , Lutsenko Nataliia 
Published: October 2019

Background: Transvaginal sonography (TVS) is considered a simple and generally accepted method for detecting uterine anomalies. With TVS, the uterus can be clearly visualized, but so far, the diagnostic accuracy of TVS varies across different studies. This retrospective study was devised to evaluate the accuracy of a sonographic diagnosis of endometrial polyps in a Ukrainian hospital. Methods: This was a single-center retrospective study of woman who underwent TVS and had hysteroscopy or dilation and curettage for endometrial pathology. A cohort of 156 women were included in this yearlong study. A comparative analysis was based on the preoperative diagnosis, according to TVS, compared with the postoperative histopathology results. Results: The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of TVS in diagnosing endometrial polyps were 69%, 51%, 73%, 46%, and 63%, respectively. Conclusion: This retrospective study provided data on the lack of accuracy for a sonographic diagnosis of endometrial polyps. This was based on 26% of women whose diagnosis was not confirmed by histology. A false-negative result occurred for 54% of women who had polyps that were not detected at the preoperative stage. These data raise the question of the feasibility of further invasive procedures based on a single TVS study.
Crystal chemistry and nomenclature of rhodonite-group minerals
Authors: Shchipalkina Nadezhda V. , Pekov Igor V. , Chukanov Nikita V. , Biagioni Cristian , Pasero Marco 
Published: October 2019

AbstractThis paper presents the nomenclature of the rhodonite group accepted by the Commission on New Minerals, Nomenclature and Classification of the International Mineralogical Association (IMA). An overview of the previous studies of triclinic (space group P$\bar{1}$) pyroxenoids belonging to the rhodonite structure type, with a focus on their crystal chemistry, is given. These minerals have the general structural formula VIIM(5)VIM(1)VIM(2)VIM(3)VIM(4)[Si5O15]. The following dominant cations at the M sites are known at present: M(5) = Ca or Mn2+, M(1–3) = Mn2+; and M(4) = Mn2+ or Fe2+. In accordance with the nomenclature, the rhodonite group consists of three IMA-approved mineral species having the following the general chemical formulae: M(5)AM(1–3)B3M(4)C[Si5O15], where A = Ca or Mn2+; B = Mn2+; and C = Mn2+ or Fe2+. The end-member formulae of approved rhodonite-group minerals are as follows: rhodonite CaMn3Mn[Si5O15]; ferrorhodonite CaMn3Fe[Si5O15]; and vittinkiite MnMn3Mn[Si5O15].
Adult T Cell Leukemia/Lymphoma Development in HTLV-1-Infected Humanized SCID Mice.
Authors: Banerjee Prabal , Lairmore Michael D , Ramos Juan Carlos , Harrington William J , Beilke Mark A , Feuer Gerold 
Published: October 2019

Abstract
Abstract 1425
Poster Board I-448
Human T-lymphotropic virus type-1 (HTLV-1) is the first human retrovirus linked to cancer and is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive CD4+ T cell malignancy. The molecular and genetic factors induced by HTLV-1 that initiate ATLL remain unclear, in part, due to the lack of an animal model which recapitulates leukemogenic events. In particular, early target cell infection and transformation events have not been identified or defined. Herein, we have created humanized NOD/SCID (HU-NOD/SCID) mice by inoculation of NOD/SCID mice with CD34+ hematopoietic progenitor and stem cells (CD34+ HP/HSCs) infected ex vivo with HTLV-1. HTLV-1-HU-NOD/SCID mice consistently developed CD4+ T cell lymphomas with characteristics similar to ATLL. Elevated proliferation of infected human stem cells (CD34+CD38−) in the bone marrow was observed in mice developing malignancies. Furthermore, examination of CD34+ HP/HSCs from HTLV-1-infected patients revealed proviral integrations suggesting a role of human bone marrow-derived stem cells in leukemogenesis. NOD/SCID mice reconstituted with CD34+ HP/HSCs transduced with a lentivirus vector (LV) expressing the HTLV-1 oncoprotein (Tax1) also developed CD4+ lymphomas. The recapitulation of a CD4+ T cell lymphoma in HTLV-1- and Tax1-HU-NOD/SCID mice suggest that hematopoietic stem cells serve as a viral reservoir in vivo and provide a cellular target for cell transformation in humans. This animal model of HTLV-1 induced ATLL will provide an important tool for the identification of molecular and cellular events that control the initiation and progression of the lymphoma and potential therapeutic targets to block tumor development.

Disclosures:
No relevant conflicts of interest to declare.
Treatment with Bortezomib Overcomes Resistance to Imatinib in Ph-Leukemia Quiescent Cells.
Authors: Kuwatsuka Yachiyo , Minami Yosuke , Tanizaki Ryohei , Minami Miho , Abe Akihiro , Nomura Yuka , Kiyoi Hitoshi , Naoe Tomoki 
Published: October 2019

Abstract
Abstract 1426
Poster Board I-449
Recent studies suggest that leukemia stem cells (LSCs) are responsible for relapse of leukemia following conventional or targeted agents and that eradication of LSCs might be necessary to cure the disease. In order to examine mechanisms of drug resistance in LSCs and to seek strategies to overcome the resistance, we used Ph-positive acute lymphoblastic leukemia patient cells serially xenotransplanted into immunodeficient NOD/SCID/IL2rγnull (NOG) mice. Engrafted bone marrow and spleen cells were almost identical to the original leukemia cells as to phenotypes including karyotypes and distribution of primitive populations. Recently several publications have suggested that proteasome inhibitors can induce selective cell death in LSCs. Spleen cells derived from leukemic NOG mice were treated ex vivo with imatinib and the proteasome inhibitor, bortezomib and cell viablility (PI-/Annexin-V-) was compared between treated and non-treated cells. After treatment with imatinib, significantly more residual cells were observed in the CD34+CD38- population compared to the CD34+CD38+ or CD34-CD38+ populations. With nM level of bortezomib, substantial cell death was induced in all populations with up-regulation of phospho-p53 (Ser15). Phosphorylation of BCR-ABL and CrkL was completely inhibited in all populations with imatinib treatment, but not with bortezomib treatment. Regarding cell cycle states, a higher percentage of Hoechst-33342low/Pyronin-Ylow cells was observed in the CD34+CD38- population relative to the other populations, suggesting more cells in the G0 state among the CD34+CD38- population. In co-culturing with S17 stromal cells, quiescent (Hoechst-33342low/Pyronin-Ylow) CD34+ cells were insensitive to imatinib, while substantial cell death including CD34+ population was induced with nM level of bortezomib. We are also investigating more detailed biomarkers in the cell death and effects of these drugs both on the primitive leukemia cells and normal hematopoietic cells using the in vivo leukemic NOG mice systems. These results imply that resistance to imatinib in Ph-positive leukemia quiescent cells is independent of BCR-ABL phosphorylation and that treatment with bortezomib can overcome the resistance of Ph-positive LSCs.

Disclosures
Kiyoi: Kyowa Hakko Kirin: Consultancy. Naoe: Kyowa Hakko Kirin, Wyeth and Chugai: Research Funding.
An Expanded Set of Direct BLIMP-1 Targets Identifies Novel Links in Differentiation, Immune Response and Lymphoma.
Authors: Tooze Reuben M , Care Matthew A , Westhead David R , Doody Gina M 
Published: October 2019

Abstract
Abstract 1466
Poster Board I-489
B-lymphocyte induced maturation protein 1 (BLIMP-1) has been defined as a key driver of the genetic reprogramming during differentiation of B-cells to plasma cells. Frequent inactivation of PRDM1, the BLIMP-1 gene, in diffuse large B-cell lymphoma (DLBCL) indicates that loss of function is an important event in lymphomagenesis. Only a limited set of direct BLIMP-1 target genes have been defined. In order to better understand the function of human BLIMP-1 in differentiation and malignancy we have established a more comprehensive set of occupied promoters. These data provide an extended view of the regulatory network controlled by BLIMP-1, and identify novel sets of targets involved in transcription and immune response. The composition of occupied promoters identifies complexity in BLIMP-1 binding motif selection, and substantial overlap between BLIMP-1 sites and Interferon regulatory factor (IRF) elements. Consistent with active competition between BLIMP-1 and IRFs, target genes associated with such overlapping motifs are found to be preferentially induced in response to BLIMP-1 knockdown. Finally BLIMP-1 targets are found to include key components of DLBCL gene expression signatures. This map of BLIMP-1 occupied promoters thus illuminates key aspects of function in normal and malignant cell biology.

Disclosures:
No relevant conflicts of interest to declare.
C6-Deficient Mice Are Protected From the Pathogenic Effects of Antiphospholipid Antibodies.
Authors: Carrera-Marin Ana Laura , Romay-Penabad Zurina , Aguilar-Valenzuela Renan , Martinez-Martinez Laura Aline , Papalardo Elizabeth , Pierangeli Silvia S 
Published: October 2019

Abstract
Abstract 147

Background:
The pathogenic mechanisms mediated by antiphospholipid (aPL) antibodies are only partially understood. Tissue factor (TF) upregulation has been shown to play an important role and recent studies have demonstrated that mice deficient in complement C3, C5 or C5a receptor (R) are resistant to the thrombogenic effects of aPL antibodies. The complement membrane attack (C5b-9 MAC) complex has been shown to bind specific receptors, to induce TF expression and to exert procoagulant effect in various cell types (i.e. endothelial cells). However whether C5b-9 MAC plays a role in the pathogenesis of thrombosis in Antiphospholipid Syndrome (APS) is unknown. Here we addressed that question by studying the effects of human aPL antibodies on thrombosis and TF upregulation in C6 deficient (−/−) mice.

Methods:
C6 deficient (−/−) mice and the corresponding wild-type (WT) mice C3H/HeJ (C6+/+) were injected twice with 500γg/ml IgG isolated from a patient with APS (IgG-APS) or with the corresponding control IgG-NHS. Seventy-two h after the first injection the size of induced thrombi in the femoral vein, IgG anticardiolipin (ACL) activity in the sera were determined. TF activity was determined in homogenates of carotid arteries and in peritoneal macrophages using a chromogenic assay.

Results:
Thrombus sizes were significantly larger in WT mice C6 (+/+) treated with IgG-APS when compared with C6 (+/+) mice treated with IgG-NHS (p= <0.001) The sizes of thrombi were significantly smaller in the C6 (−/−) mice injected with IgG-APS compared to their WT C6 (+/+) counterparts (p= <0.001) showing an important abrogation of thrombus formation in mice lacking C6. Thrombus sizes in C6 (−/−) mice injected with IgG-NHS were not different when compared to C6 (+/+) mice treated with IgG-NHS (p= 0.786), Similarly, upregulation of TF activity in carotid arteries homogenates and in peritoneal macrophages in C6 (+/+) mice treated with IgG-APS were significantly diminished in C6 (−/−) mice (p=0.036 and p=0.041, respectively). All mice injected with IgG-APS had medium-high titers of aCL in their serum (see Table)

Conclusions:
These data indicate that the C6 component of the complement system mediates aPL-thrombogenic effects and not only underscore the importance of complement activation by aPL antibodies, but also propose its inhibition as a possibly novel therapeutic target for thrombosis in APS .

Disclosures:
No relevant conflicts of interest to declare.
PU.1 Is Indispensable for Development of Mature Dendritic Cells and Their Function That Plays a Critical Role in Maintenance of Normal T Cell Pool.
Authors: Iino Tadafumi , Jeong Yong , Mizuno Shin-ichi , Kohno Kentaro , Ito Kyoko , Tenen Daniel G. , Reizis Boris , Akashi Koichi 
Published: October 2019

Abstract
Abstract 1471
Poster Board I-494
PU.1, a hematopoietic transcription factor, is indispensable for development of myelo-lymphoid cells from hematopoietic stem cells (HSCs). PU.1-deficient mice fail to develop common myeloid progenitors (CMPs) or common lymphoid progenitors (CLPs), resulting in complete loss of dendritic cells (DC) in addition to mature myeloid and lymphoid cells. By disrupting PU.1 specifically at the mature DC stage, we here show that PU.1 is necessary for maintenance of mature DC pool and their functions. We crossed PU.1 floxed/floxed mice with a mouse line harboring the Cre transgene driven by the CD11c-BAC. In these mice, PU.1 gene was disrupted in all conventional DCs but not in other hematopoietic cells, including lymphoid cells, myeloid cells and their progenitors. Development of DC precursors such as Lin−c-KitloFLT3+MCSFR+, FLT3+ CLP and FLT3+CMP were not affected. The number of CD11c+B220− DCs, however, significantly reduced in all lymphoid tissues including the thymus, the spleen, the lymph node and the skin, down to <40%, <25%, <10% and <5% as compared with the wild-type control, respectively. Moreover, the number of mature T cells reduced to ∼60% in the spleen as compared to the control. PU.1-deficient DCs displayed impaired functions to induce antigen-driven T cell proliferation, and to produce inflammatory cytokines (TNFa, IL-6, IL-12) in response to Toll like receptor (TLR) stimulation. These results clearly show that PU.1 is required for development of the peripheral DC pool and for maintenance of their immunological functions, which might be required for maintenance of the peripheral T cell pool.

Disclosures:
No relevant conflicts of interest to declare.
Elevated Levels of Tissue Factor Bearing Microparticles in Patients with Antiphospholipid Antibodies: Analysis of Fresh, Unfrozen Samples.
Authors: Khan Mohammad , Cockrell Erin , Espinola Ricardo , Bartholomew John R. , McCrae Keith R. 
Published: October 2019

Abstract
Abstract 148

Introduction:
The antiphospholipid syndrome (APS) is characterized by venous or arterial thrombosis, and/or recurrent fetal loss in the presence of circulating antiphospholipid antibodies (APL). The pathogenesis of this disorder may involve, in part, the activation of vascular endothelial cells, platelets, and monocytes. Upon activation, these cells shed components of their plasma membranes as microparticles (MP), and procoagulant MPs are associated with an increased risk for thromboemboli. The goal of these studies was to characterize, for the first time, the frequency by which increased levels of endothelial cell, platelet and monocyte-derived microparticles are observed in freshly-obtained, unfrozen plasma from patients with APL.

Patients and Methods:
Whole citrated (3.2%) blood samples from patients/healthy donors were centrifuged at 1500xg for 15 min, and the supernatant further centrifuged at 13000xg for 2 min to obtain platelet free plasma (PFP). To detect microparticles, and their origin, PFP was labeled with the following conjugated monoclonal antibodies and analyzed by flow cytometry using an LSR II flow cytometer (BD): Annexin V-APC; CD105-PE and CD144-PE (endothelial cells); CD41-PECy5 (platelets); CD14-PE (monocytes); and anti-tissue factor mAb-Alexa Fluor 647 (a kind gift from Dr. Kenneth Mann, Univ of VT). The binding of control antibodies labeled with identical fluorophores as the monoclonal antibodies was subtracted to adjust for nonspecific binding. We assessed microparticles in 47 patients with APL and 144 healthy controls.

Results
Levels of annexin-V, CD105, CD144, CD41 and tissue factor positive microparticles were significantly higher in patients (47,000±7900, 10,140±2164, 46,690±8783, 127,200±28,050 and 7270±2810 microparticles/ml, respectively) versus controls (17,000±1800, 3,824±374, 17,320±2636, 54,910±7132 and 2,537±747 microparticles/ml, respectively). These differences were statistically significant. In contrast, there was no significant difference in CD14 positive microparticle levels (1035±167 in APL patients versus 1409±465 in controls; p=0.655).

Conclusions:
Our results demonstrate elevation of annexin V+, CD105+, CD144+, CD41+ and tissue factor-bearing microparticles in freshly-obtained, unfrozen plasma obtained from patients with APL. These results suggest that ongoing activation of platelets and endothelial cells occurs in many patients with APL even in the absence of active thrombosis, and may contribute to the prothrombotic phenotype of these patients. Data is currently being analyzed for associations of microparticle levels with APL serologies, as well as the expression of functional microparticle-associated tissue factor activity.

Disclosures:
No relevant conflicts of interest to declare.