tbuckley/cabot-search huggingface dataset:
Response to Comment on Pinsker et al. Randomized Crossover Comparison of Personalized MPC and PID Control Algorithms for the Artificial Pancreas. Diabetes Care 2016;39:1135–1142
Authors: Jordan E. Pinsker, Joon Bok Lee, Eyal Dassau, Dale E. Seborg, Paige K. Bradley, Ravi Gondhalekar, Wendy C. Bevier, Lauren Huyett, Howard C. Zisser, Francis J. Doyle
Journal: Diabetes Care (2016)

We thank Dr. Steil (1) for critically reviewing our study comparing model predictive control (MPC) and proportional integral derivative (PID) control for the artificial pancreas (2). We agree that MPC and PID both come in many variants and that there are many successful trials of PID control for automated insulin delivery. We acknowledged in our study that both controllers performed very well overall, even after the 65-g unannounced meal was accounted for, and did so with low rates of hypoglycemia.

We recognize the value in comparing results across different studies and want to emphasize that we did not intend to dismiss studies with different designs. However, it is not possible to have an equitable comparison of MPC versus PID controllers through such meta-analyses. Our study was specifically designed for as fair and balanced a comparison as possible between the …
Abstract 4985: Notch1 as a key mediator in promoting advanced castration-resistant prostate cancer
Authors: Tanya Stoyanova, Claire Faltermeier, Bryan Smith, Andrew Goldstein, Xi Zhang, Justin Drake, John Lee, Sandra Orellana, Steven Blum, Donghui Cheng, Kenneth Pienta, Jiaoti Huang, Owen Witte
Journal: Cancer Research (2015)

Abstract The first line of treatment for men with advanced prostate cancers is androgen deprivation therapy. However, the disease commonly relapses in its lethal metastatic form referred to as castration-resistant prostate cancer (CRPC). CRPC is the primary cause of prostate cancer specific mortality in men. Current therapies including chemotherapeutic agents improve median overall survival by only few months. The mechanisms that distinguish clinically localized indolent tumors from lethal CRPC are unclear. Here we demonstrate that ectopic expression of Notch1 promotes progression to poorly differentiated carcinoma when combined with pathways that are altered in advanced disease but are insufficient to drive aggressive prostate cancer alone. Notch1 driven tumors are resistant to androgen deprivation. Transcriptional profiling reveals that these tumors display features of epithelial to mesenchymal transition, a morphological change associated with tumor aggressiveness and metastasis. Our study provides the first functional evidence that Notch1 signaling axis is a key mediator in promoting advanced prostate cancer and may represent a new therapeutic target for the advanced disease. Note: This abstract was not presented at the meeting. Citation Format: Tanya Stoyanova, Claire Faltermeier, Bryan Smith, Andrew Goldstein, Xi Zhang, Justin Drake, John Lee, Sandra Orellana, Steven Blum, Donghui Cheng, Kenneth Pienta, Jiaoti Huang, Owen Witte. Notch1 as a key mediator in promoting advanced castration-resistant prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4985. doi:10.1158/1538-7445.AM2015-4985
51. LV. InsB9-23/Anti-CD3 mAb Inhibits Recurrence of Autoimmunity in NOD Mice After Islet Transplants
Authors: Fabio Russo, Maria Grazia Roncarolo, Andrea Annoni
Journal: Molecular Therapy (2016)

Type 1 diabetes (T1D) is an autoimmune disease resulting in complete destruction of insulin-producing pancreatic beta-cells, which is mediated by auto-reactive T cells. In T1D in human and in the non-obese diabetic (NOD) mouse, the spontaneous murine model of T1D, induction of tolerance to beta-cell associated antigens represents a potential curative option. We previously showed that systemic administration of a single dose of integrase-competent (IC) or integrase-defective (ID) LV.ET. InsB9-23.142T (LV.InsB), enabling stable or transient expression of InsB9-23 in hepatocytes, arrests beta-cell destruction in NOD mice at advanced pre-diabetic stage. In these mice stable normoglycemia is maintained long term and InsB9-23-specific FoxP3+ T regulatory cells (Tregs) are generated. Moreover, LV. InsB in combination with a suboptimal dose (1X 5µg) of anti-CD3 mAb reverts overt diabetes and preserves residual beta-cell mass. In the present study we tested the efficacy of the LV.InsB/anti-CD3 combination therapy to inhibit recurrence of autoimmunity and maintain insulin independence after pancreatic islets transplants. Pancreatic islets isolated from NOD-scid donor mice were transplanted under the kidney capsule of diabetic NOD mice with blood glucose levels >350mg/dL. Successfully transplanted mice (normoglycemic: blood glucose levels ~100 mg/dL) were treated with LV.InsB/anti-CD3; anti-CD3 mAb (1X 5µg) alone or left untreated as controls. LV.InsB/anti-CD3 combination therapy allowed stable normoglycemia up to 250 days whereas in mice receiving anti-CD3 mAb alone or untreated controls recurrence of diabetogenic responses cleared transplanted islets in 2 weeks. Autoreactive T cells were still present in the spleen of transplanted mice treated with LV.InsB/anti-CD3, but the frequency of FoxP3+ Tregs within the CD4+ T cells in renal (RLN) and pancreatic (PLN) lymph nodes significantly increased, as shown by phenotypic analysis. These data show that LV. InsB/anti-CD3 treatment induces active suppression of autoimmune responses in long-term normoglycemic transplanted NOD mice. Ag-specific FoxP3+ Tregs accumulating in the PLN and RLN suppress effector T cells present in the target tissue. This mode of action is similar to what we previously described after LV. InsB treatment in a model of autoimmunity (Akbarpour M. et al. Science TM. 2015). Further studies are currently ongoing to evaluate the relative contribution of endogenous and exogenous beta-cell mass to insulin independence and to investigate the efficacy of the LV.InsB/anti-CD3 treatment after transplant of allogeneic pancreatic islets. The definition of novel gene therapy strategies to induce Ag-specific tolerance that at the same time control autoimmunity and transplant rejection would represent a major step toward the cure of type 1 diabetes.
Laser Treatments for Postinflammatory Hyperpigmentation
Authors: Oma Agbai, Iltefat Hamzavi, Jared Jagdeo
Journal: JAMA Dermatology (2016)

<h3>Importance</h3> Lasers are gaining interest as a treatment option for postinflammatory hyperpigmentation (PIH) but can pose a clinical dilemma given the risk for laser-induced or exacerbated PIH. <h3>Objective</h3> To assess the clinical evidence for the use of lasers in the treatment of PIH. <h3>Evidence Review</h3> A systematic review was performed by searching PubMed databases from January 1, 1990, through May 31, 2016. Included studies involved laser treatment for PIH with the degree of pigmentation as a measure of outcome. The search was filtered to include only clinical studies written in the English language. Study methods were analyzed and the reproducibility of the studies was graded. Outcome measures varied from study to study and included concentration of melanin and hemoglobin, patient satisfaction questionnaires, clinical photography, subjective clinical improvement, light microscopy, melanin index, reflectance spectroscopy, and/or skin biopsy evaluated by a blinded dermatopathologist. <h3>Findings</h3> Of 1295 results, 20 unique studies with 224 patients met the inclusion criteria. These studies included 1 randomized clinical observer-blinded study (6 patients), 4 nonrandomized clinical trials (133 patients), 1 cohort study (34 patients), 7 case series (44 patients), and 7 case reports (7 patients). Multiple lasers were studied; however, most of the studies were not methodologically rigorous. Some studies showed no improvement or worsening of PIH after laser treatment. The most extensively studied device was the Q-switched Nd:YAG laser, which has shown promising results based on multiple outcome measures as listed above. <h3>Conclusions and Relevance</h3> Some lasers may be beneficial in the treatment of PIH. The evidence suggests that additional studies would be required to determine the benefit of laser treatment of PIH.
Pharmacokinetic Exploration of Potential for Bendamustine to Affect Rituximab Concentrations and of Cytochrome P450 1A2 Inhibitors to Affect Bendamustine Concentrations in Patients with Non-Hodgkin and Mantle Cell Lymphoma
Authors: Mona Darwish, Mary Bond, John M. Burke, Edward T. Hellriegel, Philmore Robertson, Luann Phillips, Thaddeus Grasela
Journal: Blood (2012)
Outcomes Following Syngeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma: A Matched Comparison to Autologous Transplantation.
Authors: Asad Bashey, Waleska S. Perez, Mei-Jie Zhang, David H. Vesole, Donna E. Reece, Hartmut Goldschmidt, Parameswaran Hari
Journal: Blood (2006)
Cardiac Dendritic Cells and Acute Myocarditis in the Human Heart
Authors: Hiroyuki Yokoyama, Sadahito Kuwao, Ken Kohno, Keisuke Suzuki, Toru Kameya, Tohru Izumi
Journal: Circulation (2000)

Cardiac dendritic cells are considered to play an important role in the immunoresponse of the heart. However, it is unclear whether these cells occur in human myocarditis and whether they function in similar ways to those in rats. Cardiac samples were obtained from 22 autopsied patients with myocarditis, and compared with 20 age- and sex-matched controls. Formalin-fixed hearts were immunostained by the LSAB method. Cardiac dendritic cells were detectable even in the control hearts (1.5 cells/high power field (HPF)). In the acute phase of myocarditis, the number of cardiac dendritic cells increased up to 12.6 cells/HPF (p<0.001). In the subacute phase of myocarditis, T cells (36.6 cells/HPF) and HLA-DR+ cells (10.2 cells/HPF) continued to infiltrate the periphery of the inflammatory lesions, but they had no expression without inflammation. In this study, cardiac dendritic cells were reactive for HLA-DR, but negative for CD68, and were characteristically large monocytes with long, slender, dendritic processes. Accordingly, they were clearly distinguishable from macrophages. In the human heart, cardiac dendritic cells may be recruited in the acute phase of myocarditis, and seem to play an important role in the succeeding immunoresponse.
Assessment of distress among breast cancer survivors following primary treatment.
Authors: Anu Radha Neerukonda, Catherine Messina, Lisa Reagan, Michelle M. Stevens, Barbara Nemesure
Journal: Journal of Clinical Oncology (2015)

240 Background: Although elevated levels of distress have been well documented among cancer patients receiving active treatment, the magnitude of and contributors to distress in cancer survivors are yet to be well established. The purpose of this investigation was to evaluate the presence of distress among breast cancer survivors (BCS) and to investigate demographic, psychosocial, tumor and treatment related variables that may be associated with distress in this population. Methods: A retrospective chart review was done that includes 81 female BCS, 21 years or older, who received care at the Stony Brook Cancer Center Survivorship Clinic and completed the National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) form between October 2012 and June 2014. Descriptive statistics were used to describe the demographic, psychosocial, tumor and treatment characteristics for the study sample and logistic regression models were used to evaluate the relationship between elevated distress and the factors outlined above. The regression results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Data were analyzed using SPSS version 21. Results: Approximately one-half of BCS (50.6%) reported a clinically significant distress level (4 or higher). Those who were on an anxiolytic or anti-depressant medication tended to have higher levels of distress (OR: 3.10; 95% CI: 0.90-10.74; P = 0.07) and age greater than 60 years at the time of diagnosis was negatively correlated with distress (OR: 0.24; 95% CI: 0.07-0.84; P = 0.03). BCS with clinically significant distress (4 or greater) reported more problems in the emotional domain components of the DT, whereas patients with low distress (less than 4) reported more problems on the physical domains. Conclusions: Findings from this study indicate that more than half of BCS experienced distress during the survivorship phase, which frequently manifested as emotional and physical problems. Although preliminary, these data suggest the need to develop targeted screening strategies for early recognition and interventions to alleviate distress in this population.
P0372 : Gideon: A retrospective analysis of prognostic factors for survival
Authors: J.-P. Bronowicki, M. Kudo, R. Lencioni, X.-P. Chen, L. Dagher, J. Furuse, J.-F.H. Geschwind, L. Ladrón de Guevara, C. Papandreou, A.J. Sanyal, T. Takayama, S.K. Yoon, K. Nakajima, S.-L. Ye, J.A. Marrero
Journal: Journal of Hepatology (2015)
KRN5500, a Spicamycin Derivative, Exerts Anti-Myeloma Effects through Impairing Both Myeloma Cells and Osteoclasts.
Authors: Hirokazu Miki, Shuji Ozaki, Osamu Tanaka, Shingen Nakamura, Ayako Nakano, Kumiko Kagawa, Kyoko Takeuchi, Kenichiro Yata, Masahiro Abe, Toshio Matsumoto
Journal: Blood (2008)
Chasing crystals out of the body: will treat to serum urate target for gout help us get there?
Authors: Jasvinder A Singh, Till Uhlig
Journal: Annals of the Rheumatic Diseases (2016)

In this issue of the journal, Kiltz et al published the treat-to-target (T2T) recommendations for gout, 1 based on a systematic literature review (SLR) using standard methodology based on Oxford Center for Evidence-based Medicine system and the AGREE criteria. 2 3The expert group developed nine T2T recommendations for gout management.
A Psychosocial Assessment of Patients before and after Autologous Stem Cell Transplantation.
Authors: Brian J. Bolwell, Linda McLellan, Larry Foster, Jane Dabney, Erin Welsh, Elizabeth Kuczkowski, Julie Curtis, Kimberly Bell, Janet Baker, Laura Bernhard, Kelly Cherni, Lisa Rybicki, Mikkael A. Sekeres
Journal: Blood (2004)
Capecitabine, oxaliplatin and irinotecan (COI regimen) as perioperative treatment of resectable gastric or gastroesophageal junction (GEJ) cancer
Authors: R. Berenato, F. Pietrantonio, M. Niger, M. Caporale, F. Ricchini, C. Maggi, I. Bossi, P.V. Consonni, F. de Braud, M. Di Bartolomeo
Journal: Annals of Oncology (2015)
A Phase I/II Study of the Oral mTOR Inhibitor RAD001 in Patients with Advanced Hematologic Malignancies.
Authors: Karen W.L. Yee, William Wierda, Susan O’Brien, Deborah Thomas, Razelle Kurzrock, Luis E. Fayad, Fredrick B. Hagemeister, Jorge Cortes, Judith Prestifilippo, Ted P. Szatrowski, Hagop M. Kantarjian, Francis J. Giles
Journal: Blood (2004)
P-271 Retrospective Cohort Study on the Safety and Efficacy of Regorafenib for Metastatic Colorectal Cancer Patients: The HGCSG1401 Study -First Report-
Authors: S. Yuki, Y. Komatsu, T. Muranaka, S. Yoshida, Y. Ohta, K. Hatanaka, Y. Tsuji, Y. Kawamoto, K. Yoshizaki, A. Sato, K. Eto, K. Onodera, S. Kato, M. Nakamura, O. Muto, M. Abe, Y. Sato, A. Ishiguro, M. Tateyama, H. Okuda, N. Sakamoto, Y. Sakata
Journal: Annals of Oncology (2015)
Ibritumomab Tiuxetan (Zevalin) in the Conditioning Regimen for Autologous and Reduced-Intensity Allogeneic Stem-Cell Transplantation in Patients with Chemo-Refractory Non-Hodgkin’s Lymphoma.
Authors: Avichai Shimoni, Tsila Zwas, Yaacov Oksman, Izhar Hardan, Noga Shem-Tov, Ronit Yerushalmi, Abraham Avigdor, Isacc Ben-Bassat, Arnon Nagler
Journal: Blood (2005)
Abstract 4886: Repair of challenging FFPE DNA improves library success rate and sequencing quality
Authors: Pingfang Liu, Lixin Chen, Laurence Ettwiller, Christine Sumner, Fiona Stewart, Eileen Dimalanta, Theodore Davis, Thomas Evans
Journal: Cancer Research (2015)

Abstract Formalin-fixed, paraffin-embedded (FFPE) clinical samples are an invaluable source of information about genetic alterations in human disease, especially cancer. Next generation sequencing is a powerful tool to mine that information. Unfortunately, sequencing DNA from FFPE samples is challenging due to limited quantities and poor quality, a result of DNA damage incurred during fixation and storage. In this study, we investigated the effects of DNA repair on library preparation and sequencing from FFPE samples. We evaluated a repair enzyme mix that is designed to work on a broad range of DNA damage including modified bases, nicks, gaps, and blocked 3′ ends. Results from FFPE DNA samples of varying quality show that DNA repair generally increases library yields by 10-170%, with the largest improvement on samples of poor quality. Careful analysis of sequencing data shows that base calling qualities for all 4 bases are improved upon DNA repair. Aberrant G:C to A:T mutation were significantly reduced, consistent with cytosine deamination being induced during fixation and storage at room temperature. Interestingly, sequencing miscalls for base pair changes not typically associated with fixation were also reduced. We are currently investigating the source of these mutations. With DNA repair a noticeably positive impact on read mapping and read pairing was observed, resulting in the generation of more useable data. Pretreatment of FFPE DNA by the repair enzyme mix is easily implemented upstream of library construction, allowing fast turnaround time and easy automation. We expect that these improvements will enable the analysis of many FFPE samples that would otherwise not be accessible. Citation Format: Pingfang Liu, Lixin Chen, Laurence Ettwiller, Christine Sumner, Fiona Stewart, Eileen Dimalanta, Theodore Davis, Thomas Evans. Repair of challenging FFPE DNA improves library success rate and sequencing quality. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4886. doi:10.1158/1538-7445.AM2015-4886
Abstract 2864: Acetylation regulates TET2 stability and enzymatic activity
Authors: Yang Zhang, Yi Cai, Wenbing Xie, Hariharan Easwaran, Stephen B. Baylin
Journal: Cancer Research (2015)

Abstract DNA methylation, one of the key epigenetic modifications in the mammalian genome, plays fundamental roles in development and disease. Although DNA methylation and DNA methyltransferases (DNMTs) have been studied intensively, our knowledge about DNA demethylation is just starting to emerge. The Ten-eleven translocation (TET) family of proteins are newly identified methylcytosine dioxygenases/demethylases that can oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), and promote DNA demethylation either passively through DNA replication, or actively via thymine DNA glycosylase (TDG)-mediated base excision repair. TET-mediated DNA demethylation has also been shown to play important roles in diverse biological processes and tumorigenesis. Human TET2 is frequently mutated in myeloid malignancies, while loss of 5hmC and TETs expressions have been broadly observed in many other cancer types. Recent studies suggested that TETs may be regulated by microRNAs and calpain proteases, but, overall, the regulation of TET activities is not well outlined. Here we show, in human ovarian cancer cells, that TET2 activity may be significantly modulated by post-translational modifications. TET2 is acetylated by p300/CBP at K110/111, and this acetylation can be reversed by HDAC1/2 and SIRT1/2 deacetylases. Acetylation increases TET2 stability by protecting it from ubiquitination and proteasome-mediated degradation. Interestingly, DNMT1 physically associates with and stabilizes TET2 protein, and a TET2 acetylation deficient mutant (2KR) disrupts this association, indicating that acetylation of TET2 may stimulate DNMT1 binding which prevents TET2 from degradation. In addition, we show that acetylation increases TET2 enzymatic activity. Treatment of cells with HDAC inhibitors TSA/NAM, or knocking down HDAC1/2, significantly increases global 5hmC levels. Consistent with these latter observations, the 2KR mutant almost completely abolishes TET2 catalytic activity, and this mutant protein is less efficient in forming dimer with wild type TET2. Thus acetylation events may increase the activity of TET2 through enhanced dimerization of the protein. Taken together, our study reveals a novel acetylation-dependent regulatory mechanism controlling the function of TET2. Citation Format: Yang Zhang, Yi Cai, Wenbing Xie, Hariharan Easwaran, Stephen B. Baylin. Acetylation regulates TET2 stability and enzymatic activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2864. doi:10.1158/1538-7445.AM2015-2864
No Evidence for Constitutively Activated FLT3 in Juvenile Myelo-Monocytic Leukemia.
Authors: Andrica C.H. de Vries, Ronald W. Stam, Pauline Schneider, Charlotte M. Niemeyer, Elisabeth R. van Wering, Christian Kratz, Oskar A. Haas, Monique L. den Boer, Rob Pieters, Marry M. van den Heuvel-Eibrink
Journal: Blood (2005)
Lymphocyte Survival and Activation in Stored Platelet Concentrates After Gamma-Irradiation or Pathogen Reduction Technology Treatment.
Authors: Jolanta J Wozniak, Agnieszka Krzywdzinska, Elzbieta Lachert, Karolina Janik, Jolanta Antoniewicz-Papis, Joanna Kopec-Szlezak, Magdalena Letowska
Journal: Blood (2009)
Abstract 3475: Diurnal suppression of EGFR signaling by glucocorticoids: implications for tumor progression and treatment
Authors: Mattia Lauriola, Yehoshua Enuka, Amit Zeisel, Gabriele D'Uva, Lee Roth, Silvia Carvalho, Rossella Solmi, Eytan Domany, Yosef Yarden
Journal: Cancer Research (2015)

Abstract Signal transduction by receptor tyrosine kinases (RTKs) and nuclear receptors for steroid hormones is essential for body homeostasis, but the crosstalk between these receptor families is poorly understood. We observed that activation of GR, a steroid hormone receptor that binds glucocorticoids, inhibits the transcriptional response downstream to EGFR signaling, an RTK. The underlying mechanism entails suppression of EGFR's positive feedback loops, such as ligands and simultaneous triggering of negative feedback loops that normally restrain EGFR. Our animal studies reveal that the regulation of EGFR's feedback loops by glucocorticoids translates to circadian control of EGFR signaling: EGFR signals are suppressed by high glucocorticoids during the active phase, while EGFR signals are enhanced during the resting phase. Consistent with this pattern, treatment of animals bearing EGFR-driven tumors with a specific kinase inhibitor was more effective if administered during the resting phase of the day, when glucocorticoids are low. These findings support a circadian clock-based paradigm in cancer therapy. Citation Format: Mattia Lauriola, Yehoshua Enuka, Amit Zeisel, Gabriele D'Uva, Lee Roth, Silvia Carvalho, Rossella Solmi, Eytan Domany, Yosef Yarden. Diurnal suppression of EGFR signaling by glucocorticoids: implications for tumor progression and treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3475. doi:10.1158/1538-7445.AM2015-3475