tbuckley/cabot-search huggingface dataset:
Impact of a Novel Diabetes Support System on a Cohort of Individuals With Type 1 Diabetes Treated With Multiple Daily Injections: A Multicenter Randomized Study
Authors: Alessandro Bisio, Stacey Anderson, Lisa Norlander, Grenye O’Malley, Jessica Robic, Selassie Ogyaadu, Liana Hsu, Camilla Levister, Laya Ekhlaspour, David W. Lam, Carol Levy, Bruce Buckingham, Marc D. Breton
Journal: Diabetes Care (2021)

OBJECTIVE Achieving optimal glycemic control for many individuals with type 1 diabetes (T1D) remains challenging, even with the advent of newer management tools, including continuous glucose monitoring (CGM). Modern management of T1D generates a wealth of data; however, use of these data to optimize glycemic control remains limited. We evaluated the impact of a CGM-based decision support system (DSS) in patients with T1D using multiple daily injections (MDI). RESEARCH DESIGN AND METHODS The studied DSS included real-time dosing advice and retrospective therapy optimization. Adults and adolescents (age &amp;gt;15 years) with T1D using MDI were enrolled at three sites in a 14-week randomized controlled trial of MDI + CGM + DSS versus MDI + CGM. All participants (N = 80) used degludec basal insulin and Dexcom G5 CGM. CGM-based and patient-reported outcomes were analyzed. Within the DSS group, ad hoc analysis further contrasted active versus nonactive DSS users. RESULTS No significant differences were detected between experimental and control groups (e.g., time in range [TIR] +3.3% with CGM vs. +4.4% with DSS). Participants in both groups reported lower HbA1c (−0.3%; P = 0.001) with respect to baseline. While TIR may have improved in both groups, it was statistically significant only for DSS; the same was apparent for time spent &amp;lt;60 mg/dL. Active versus nonactive DSS users showed lower risk of and exposure to hypoglycemia with system use. CONCLUSIONS Our DSS seems to be a feasible option for individuals using MDI, although the glycemic benefits associated with use need to be further investigated. System design, therapy requirements, and target population should be further refined prior to use in clinical care.
Novel Combination Therapy of Venetoclax and Ruxolitinib in the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia
Authors: Uma Borate, Jennifer N. Saultz, Andy Kaempf, Jessica Minnier, Cristina E. Tognon, Stephen E. Kurtz, Christopher A. Eide, Prapti A. Patel, Yazan F. Madanat, Peter Clement, Sammantha Avaylon, Shikha Misra, Brian J. Druker, Jeffrey W. Tyner
Journal: Blood (2021)
Abstract 9022: Chronic Beta3-Adrenergic Receptor Antagonist Therapy Rescues Diabetic Cardiomyopathy Through Ca2+/Calmodulin-Dependent Protein Kinase II Inhibition in a Type II Diabetes Murine Model
Authors: Heng Cheng, Xiaoqiang Sun, Jing Cao, Zhe Chen, Yixi Liu, David M Herrington, David Zhao, Donald McClain, Dalane W Kitzman, Che Ping Cheng
Journal: Circulation (2021)

Background: Recent evidence showed that CaMKII inhibition with KN93 protects against diabetic cardiomyopathy (DCM). However, the off-target effects have limited its use. There are no CaMKII inhibit...
Pomalidomide-Dexamethasone Effectiveness in t(11;14) Positive Relapsed Multiple Myeloma in Real-World Setting
Authors: Sudeep Karve, Shaji Kumar, Veronica Gonzalez De La Calle, Silvia Mangiacavalli, Chang-Ki Min, Efstathios Kastritis, Graca Esteves, Michel Delforge, Fernando Escalante, Jin Lu, Yang Liu, Max Bittrich, Charalampia Kyriakou, Andrew J. Yee, Emma Arriola, Jeremy A. Ross, Shivaji Manthena, Brian G.M. Durie
Journal: Blood (2021)
Abstract 11147: Associations of Physical and Mental-Health Related Quality of Life and Sleep Disturbance with Cardiovascular Disease Risk in Post-Menopausal Breast Cancer Survivors
Authors: Alexi Vasbinder, Oleg Zaslavsky, Susan R Heckbert, Hilaire J Thompson, Richard Cheng, Nazmus Saquib, Robert B Wallace, Reina Haque, electra paskett, Kerryn Reding
Journal: Circulation (2021)

Introduction: Lower health-related quality of life (HRQoL) and greater sleep disturbance (SD) are associated with an increased risk of cardiovascular disease (CVD) in the general population. However, these associations may differ in breast cancer (BC) survivors who experience competing risks from cancer and its associated treatment. We examined whether physical or mental HRQoL (including individual subscales) or SD were associated with CVD risk in BC survivors. Methods: We conducted a longitudinal analysis in the Women’s Health Initiative (WHI) of post-menopausal women free of prevalent CVD at baseline and diagnosed with invasive BC during study follow-up from 1993 - 2010. CVD was defined as physician-adjudicated coronary heart disease or stroke. Physical and mental HRQoL, measured by the SF-36 Physical and Mental Component Scores (PCS and MCS, respectively), and SD, measured by the WHI Insomnia Rating Scale (IRS), were recorded post-BC diagnosis. Higher PCS and MCS scores indicate better HRQoL while higher IRS scores indicate worse SD. Time-dependent Cox proportional hazards models were used starting at BC diagnosis until 2010 or censoring adjusted for relevant confounders most proximal to or at BC diagnosis. Results: In 2,884 BC survivors, 157 developed CVD during a median follow-up of 9.5 years. After adjustment, higher PCS scores were significantly associated with a lower risk of CVD (Table). For a 5-unit difference, the risk of CVD was 9% lower for those with higher PCS scores (95% CI: 0.83, 0.99). Of the SF-36 sub-scales, higher scores on vitality, physical functioning, and general health were significantly associated with a lower risk of CVD (Table). Conclusions: In BC survivors, we found that better physical HRQoL was associated with lower CVD risk. While further research is needed to replicate these findings, our results support existing recommendations that women with breast cancer adopt health behaviors that promote physical health.
Clinical Significance of Spatial Heterogeneity in Newly Diagnosed and Relapsed Multiple Myeloma
Authors: Maximilian Merz, Lei Wei, Qiang Hu, Almuth Maria Anni Merz, Jie Wang, Ahmed Belal, Ronald Alberico, Cherie Rondeau, Kimberly Celotto, AnneMarie W. Block, Hemn Mohammadpour, Paul K. Wallace, Joseph Dennis Tario, Jesse Luce, Sean Glenn, Prashant K Singh, David Barnidge, Song Liu, Philip L. McCarthy, Jens Hillengass
Journal: Blood (2021)
Effect of Simulation-based Training on Surgical Proficiency and Patient Outcomes: A Randomised Controlled Clinical and Educational Trial
Authors: Abdullatif Aydın, Kamran Ahmed, Takashige Abe, Nicholas Raison, Mieke Van Hemelrijck, Hans Garmo, Hashim U Ahmed, Furhan Mukhtar, Ahmed Al-Jabir, Oliver Brunckhorst, Nobuo Shinohara, Wei Zhu, Guohua Zeng, John P Sfakianos, Mantu Gupta, Ashutosh Tewari, Ali Serdar Gözen, Jens Rassweiler, Andreas Skolarikos, Thomas Kunit, Thomas Knoll, Felix Moltzahn, George N Thalmann, Andrea G Lantz Powers, Ben H Chew, Kemal Sarica, Muhammad Shamim Khan, Prokar Dasgupta
Journal: European Urology (2021)
Genetic Diversity within Leukemia-Associated Immunophenotype-Defined Subclones in AML
Authors: Francesca Tiso, Thessa N. Koorenhof-Scheele, Erik Huys, Joost H.A. Martens, Aniek O. De Graaf, Bert A. van der Reijden, Saskia M. C. Langemeijer, Frank W. M. B. Preijers, Leonie I. Kroeze, Joop H. Jansen
Journal: Blood (2021)
Abstract 12757: Impact of Social Vulnerability on Cardio-Oncology Mortality in the United States
Authors: Sarju Ganatra, Sourbha Dani, Ashish Kumar, Safi U Khan, Tomas Neilan, Paaladinesh Thavendiranathan, Ana Barac, Joerg Hermann, Monika Leja, Anita M Deswal, Michael Fradley, Jennifer Liu, Bonnie Ky, Diego B Sadler, Aarti Asnani, Lauren A Baldassarre, Dipti Gupta, Eric Yang, Avirup Guha, Sherry-Ann Brown, Rishi Wadhera, Dhruv S Kazi, Jennifer P Stevens, Salim Hayek, Suzanne J Baron, Khurram Nasir, Anju Nohria
Journal: Circulation (2021)

Introduction: Racial and social disparities affect cancer and CVD-related mortality. The relationship between social vulnerability and concomitant cancer and CVD (cardio-oncology) related mortality remains understudied. Methods: We used the CDC Wide-Ranging OnLine Data for Epidemiologic Research (WONDER) database to determine the association between deaths attributed to the presence of concomitant CVD and cancer (ICD-10 codes I00-I09, I11, I13, I20-I51 and C00-C96), and the county-level social-vulnerability index (SVI). SVI measures a community’s vulnerability based on socioeconomic status, household composition, disability, minority status, language, and transportation. We aggregated counties by SVI quartiles (1st: most favorable = 0.00 to 0.25; 4th: least favorable = 0.75 to 1.00) and compared age-adjusted mortality rates (AAMRs) across SVI quartiles. Results: Between 2014 and 2018, the AAMR due to concomitant cancer and CVD was 47.75 (95% CI, 47.66- 47.85) per 100,000 person-years with higher mortality in areas with a higher SVI (Figure). Similarly, CVD and cancer-related mortality was also significantly greater in counties with the highest SVI [(CVD: 1.287 (95% CI 1.284-1.290); Cancer: 1.087 (95% CI 1.084-1.091)]. Moreover, the proportional increase in cardio-oncology mortality between the highest and lowest SVI counties was greater than that observed for CVD or cancer-associated mortality alone (p&lt;0.001). This difference was most striking in adults &lt; 45 years, females, Asian and Pacific Islanders, and Hispanics. Conclusion: A graded increase in cardio-oncology mortality is observed in counties with higher social vulnerability. The incremental impact of SVI was greater for cardio-oncology mortality than for cancer or CVD mortality alone, particularly in certain demographic groups. These findings highlight the need for targeted resource allocation and public health interventions to address social inequities in cardio-oncology.
Gut microbiota of adults with asthma is broadly similar to non-asthmatics in a large population with varied ethnic origins
Authors: Robert F. J. Kullberg, Bastiaan W. Haak, Mahmoud I. Abdel-Aziz, Mark Davids, Floor Hugenholtz, Max Nieuwdorp, Henrike Galenkamp, Maria Prins, Anke H. Maitland-van der Zee, W. Joost Wiersinga
Journal: Gut Microbes (2021)

Bacterial gut communities might predispose children to develop asthma. Yet, little is known about the role of these micro-organisms in adult asthmatics. We aimed to profile the relationship between fecal microbiota and asthma in a large-scale, ethnically diverse, observational cohort of adults. Fecal microbiota composition of 1632 adults (172 asthmatics and 1460 non-asthmatics) was analyzed using 16S ribosomal RNA gene sequencing. Using extremely randomized trees machine learning models, we assessed the discriminatory ability of gut bacterial features to identify asthmatics from non-asthmatics. Asthma contributed 0.019% to interindividual dissimilarities in intestinal microbiota composition, which was not significant (P = .97). Asthmatics could not be distinguished from non-asthmatics based on individual microbiota composition by an extremely randomized trees classifier model (area under the receiver operating characteristic curve = 0.54). In conclusion, there were no prominent differences in fecal microbiota composition in adult asthmatics when compared to non-asthmatics in an urban, large-sized and ethnically diverse cohort.
Lenalidomide Compared to Ixazomib Maintenance in Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis
Authors: Eunice Lai, Yu Yang Soon, Ainsley Ryan Yan Bin Lee, Shi Yin Wong, Cinnie Yentia Soekojo, Melissa Ooi, Wee-Joo Chng, Sanjay De Mel
Journal: Blood (2021)
Structural and Social Barriers to Survival in Adolescent and Young Adult (AYA) Patients with Acute Myeloid Leukemia (AML)
Authors: Madelyn Burkart, Ivy Abraham, Garth Rauscher, Nepheli Raptis, Maryam Zia, Anand Ashwin Patel, Ami Dave, Stephanie Berg, Wendy Stock, Melissa L. Larson, William B Pearse, Jessica K. Altman, Irum Khan, Shira Dinner
Journal: Blood (2021)
Abstract PO-091: Histamine receptor 1 (HRH1): A potentially novel G protein-coupled receptor (GPCR) therapeutic target in pancreatic adenocarcinoma (PDAC) cells and tumors
Authors: Cristina Salmeron, Krishna Sriram, Mehrak Javadi-Paydar, Paul A. Insel
Journal: Cancer Research (2021)

Abstract A recent study reported that patients taking HRH1 antihistamines have decreased progression of various tumors, including PDAC; the authors inferred that this was an immune effect (Fritz et al., PMID: 33550204). We have initiated studies to test an alternative hypothesis: HRH1 expressed by PDAC cells may contribute to the malignant phenotype and if so, FDA-approved HRH1 antihistamines might be therapeutics to treat or perhaps prevent PDAC. We have undertaken bioinformatic and experimental approaches to test this hypothesis. Our bioinformatic analysis revealed that PDAC tumors in The Cancer Genome Atlas (TCGA) have &amp;gt;30-fold higher HRH1 expression than in normal pancreas (GTEx database) and is highly expressed in PDAC cell lines in the Cancer Cell Line Encyclopedia (CCLE). HRH1 expression was selectively associated with markers of PDAC cells and not with markers of other cell types in the tumor microenvironment. Higher expression of HRH1 in TCGA-PDAC tumors negatively impacts on patient survival. Our experimental studies indicate that human and mouse PDAC cells express HRH1 mRNA, protein and signaling and that HRH1 is present on the surface of PDAC cells. We found that histamine prominently increases calcium [Ca2+] in multiple human PDAC cell lines with EC50 values comparable to that in other cell types. The histamine-stimulated increase in [Ca2+] occurs via a Gq/11 (heterotrimeric GTP binding protein)-dependent mechanism and is blocked by multiple FDA-approved HRH1 antihistamines (with pKi values similar to those of HRH1 inhibition of other cell types). HRH1 activation by histamine increases PDAC cell migration. Histamine also increases the production of numerous cytokines (including VEGF) from PDAC cells, and in preliminary studies, stimulates growth of multiple PDAC cell lines at low concentrations (1-10 nM). Together with published data indicating that mast cells (which synthesize and release histamine) in PDAC tumors are associated with PDAC cell growth/invasion, angiogenesis and worse prognosis, our findings suggest that independent of immune cells, a "mast cell-histamine-PDAC cell HRH1 axis" may contribute to the malignant phenotype of PDAC tumors. Importantly, HRH1 on PDAC cells could be targeted by repurposing approved HRH1 antihistamines as a novel therapeutic approach for PDAC tumors. Supported by grants from the University of California Cancer Research Coordinating Committee and Tobacco-Related Disease Research Program. Citation Format: Cristina Salmeron, Krishna Sriram, Mehrak Javadi-Paydar, Paul A. Insel. Histamine receptor 1 (HRH1): A potentially novel G protein-coupled receptor (GPCR) therapeutic target in pancreatic adenocarcinoma (PDAC) cells and tumors [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-091.
Association of clonal hematopoiesis with chronic obstructive pulmonary disease
Authors: Peter G. Miller, Dandi Qiao, Joselyn Rojas-Quintero, Michael C. Honigberg, Adam S. Sperling, Christopher J. Gibson, Alexander G. Bick, Abhishek Niroula, Marie E. McConkey, Brittany Sandoval, Brian C. Miller, Weiwei Shi, Kaushik Viswanathan, Matthew Leventhal, Lillian Werner, Matthew Moll, Brian E. Cade, R. Graham Barr, Adolfo Correa, L. Adrienne Cupples, Sina A. Gharib, Deepti Jain, Stephanie M. Gogarten, Leslie A. Lange, Stephanie J. London, Ani Manichaikul, George T. O’Connor, Elizabeth C. Oelsner, Susan Redline, Stephen S. Rich, Jerome I. Rotter, Vasan Ramachandran, Bing Yu, Lynette Sholl, Donna Neuberg, Siddhartha Jaiswal, Bruce D. Levy, Caroline A. Owen, Pradeep Natarajan, Edwin K. Silverman, Peter van Galen, Yohannes Tesfaigzi, Michael H. Cho, Benjamin L. Ebert
Journal: Blood (2021)

Abstract Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the disease are incompletely understood. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related state in which somatic mutations in clonal blood populations induce aberrant inflammatory responses. Patients with CHIP have an elevated risk for cardiovascular disease, but the association of CHIP with COPD remains unclear. We analyzed whole-genome sequencing and whole-exome sequencing data to detect CHIP in 48 835 patients, of whom 8444 had moderate to very severe COPD, from four separate cohorts with COPD phenotyping and smoking history. We measured emphysema in murine models in which Tet2 was deleted in hematopoietic cells. In the COPDGene cohort, individuals with CHIP had risks of moderate-to-severe, severe, or very severe COPD that were 1.6 (adjusted 95% confidence interval [CI], 1.1-2.2) and 2.2 (adjusted 95% CI, 1.5-3.2) times greater than those for noncarriers. These findings were consistently observed in three additional cohorts and meta-analyses of all patients. CHIP was also associated with decreased FEV1% predicted in the COPDGene cohort (mean between-group differences, −5.7%; adjusted 95% CI, −8.8% to −2.6%), a finding replicated in additional cohorts. Smoke exposure was associated with a small but significant increased risk of having CHIP (odds ratio, 1.03 per 10 pack-years; 95% CI, 1.01-1.05 per 10 pack-years) in the meta-analysis of all patients. Inactivation of Tet2 in mouse hematopoietic cells exacerbated the development of emphysema and inflammation in models of cigarette smoke exposure. Somatic mutations in blood cells are associated with the development and severity of COPD, independent of age and cumulative smoke exposure.
Pancreatic islets in bed with microvasculature—companions for life
Authors: Corinne A. Hoesli, Timothy J. Kieffer
Journal: Cell Reports Medicine (2021)

In Cell Stem Cell, Aghazadeh et al.1Aghazadeh Y. Poon F. Sarangi F. Wong F.T.M. Khan S.T. Sun X. Hatkar R. Cox B.J. Nunes S.S. Nostro M.C. Microvessels support engraftment and functionality of human islets and hESC-derived pancreatic progenitors in diabetes models.Cell Stem Cell. 2021; (S1934-5909(21)00338-6)https://doi.org/10.1016/j.stem.2021.08.001Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar show that human embryonic stem cell-derived pancreatic progenitors can reverse hyperglycemia for several weeks in streptozotocin-induced diabetic mice when co-transplanted with microvessel fragments into the subcutaneous space.
Abstract 9137: Isolated Liver Perfusion and Electron Microscopy Reveal Defect in Vldl Lipidation Associated With Inactivation of Tm6sf2
Authors: Fei Luo, Justin A Fletcher, Eriks Smagris, Shawn C Burgess, Jonathan C Cohen, Helen H Hobbs
Journal: Circulation (2021)

Background: A missense variant (E167K) in Transmembrane 6 Superfamily Member 2 (TM6SF2) is associated with lower plasma lipid levels and protection from coronary artery disease. Inactivation of Tm6sf2 in mice results in increased hepatic triglyceride (TG) content associated with a reduced rate of secretion of very low-density lipoprotein (VLDL)-TG, but not VLDL-Apolipoprotein B (ApoB). To determine the mechanism responsible for the hypolipidemic effect of Tm6sf2 inactivation, we performed liver perfusion and electron microscopy studies in wildtype (WT) and Tm6sf2 -/- mice. Methods: Ad libitum chow-fed male mice (11-13 weeks old, n=4/group) Tm6sf2 -/- and age- and sex-matched WT mice (C57BL/6N background) were anaesthetized with ketamine/xylazine and treated with heparin (4U/g body weight). Livers were harvested and perfused for 60 min without recirculation with buffer contained free fatty acids (0.8 mM). VLDL was isolated from the perfusate by ultracentrifugation ( d =1.006 g/ml) and VLDL-lipids were assayed using enzymatic assays (Sigma-Aldrich) and liquid chromatography mass-spectrometry (LC-MS). Amounts of VLDL-ApoB and -ApoE were compared between strains by immunoblotting. Electron microscopy was performed on liver sections that had been stained with imidazole/osmium tetroxide to visualize lipoproteins. Results: The secretion rates of VLDL-ApoB and -ApoE did not differ between the Tm6sf2 -/- and WT mice. Hepatic secretion of VLDL lipids (TG, cholesterol, phosphatidylcholine) per ApoB was reduced by 53%, 63% and 67%, respectively, in Tm6sf2 -/- mice compared to WT controls. Electron microscopy showed that the VLDL particles in the secretory pathway of Tm6sf2 -/- mice were smaller than those in the WT animals. Conclusions: Taken together these findings are consistent with TM6SF2 reducing plasma TG and cholesterol levels through limiting addition of neutral lipids to nascent VLDL particles in the hepatocyte prior to secretion.
Insights into Endogenous Vs Exogenous Cargo-Containing Platelet Alpha-Granules
Authors: Sergey Zaytsev, Hyunsook Ahn, Victoria Stepanova, M. Anna Kowalska, Khalil Bdeir, Deborah L French, Rodney M. Camire, Douglas B. Cines, Mortimer Poncz
Journal: Blood (2021)
An Oncology Simulation Model to Estimate 10-Year Progression-Free Survival and Overall Survival Based on the 5-Year Update from the ECHELON-2 Trial in Frontline Patients with Peripheral T-Cell Lymphoma: A United States Perspective
Authors: John M. Burke, Kristina S. Yu, Uche Mordi, Brian Bloudek, Nicholas Liu, Michelle A. Fanale, Tycel Phillips
Journal: Blood (2021)
Clinical-Stage Menin Inhibitor KO-539 Is Synergistically Active with Multiple Classes of Targeted Agents in KMT2A-r and NPM1-Mutant AML Models
Authors: John A. Davis, Warren C. Fiskus, Naval Daver, Christopher Peter Mill, Christine Birdwell, Arnold Salazar, Kevin Philip, Tapan M. Kadia, Courtney D. DiNardo, Mollie Leoni, Francis Burrows, Kapil N. Bhalla
Journal: Blood (2021)
Biosimulation Using the Cellworks Computational Omics Biology Model (CBM) Predicted Novel Biomarkers for Hyper-CVAD (CVAD) Treatment Response and Combination of Rituximab and Cladribine (RC) in CVAD Resistant Cases of Mantle Cell Lymphoma (MCL)
Authors: Guido Marcucci, Ansu Kumar, Michael Castro, Swati Khandelwal, Subrat Mohapatra, Shweta Kapoor, Ashish Kumar Agrawal, Mohammed Sauban, Kabya Basu, Vijayashree P Shyamasundar, Deepak Anil Lala, Karthik Sundara Raju, Naga Ganesh Palaniyeppa, Yashaswini S Ullal, Vishwas Joseph, Liptimayee Behura, Diwyanshu Sahu, Annapoorna Prakash, Upasana Mitra, Ashokraja Balla, Mamatha Patil, Jharana Mohanty, Sanjana Patel, Michele Dundas Macpherson, Scott C Howard
Journal: Blood (2021)
Co-Operation of MCL-1 and BCL-X L Anti-Apoptotic Proteins in Stromal Protection of MM Cells from Carfilzomib Mediated Cytotoxicity
Authors: Daria Galas-Filipowicz, Selina J Chavda, Jianan Gong, David C.S. Huang, Asim Khwaja, Kwee Yong
Journal: Blood (2021)