tbuckley/cabot-search huggingface dataset:
3D‐Printed Sugar‐Based Stents Facilitating Vascular Anastomosis
Authors: Ali Farzin, Amir K. Miri, Fatemeh Sharifi, Negar Faramarzi, Arian Jaberi, Azadeh Mostafavi, Ricky Solorzano, Yu Shrike Zhang, Nasim Annabi, Ali Khademhosseini, Ali Tamayol
Journal: Advanced Healthcare Materials (2018)

Abstract Microvascular anastomosis is a common part of many reconstructive and transplant surgical procedures. While venous anastomosis can be achieved using microvascular anastomotic coupling devices, surgical suturing is the main method for arterial anastomosis. Suture‐based microanastomosis is time‐consuming and challenging. Here, dissolvable sugar‐based stents are fabricated as an assistive tool for facilitating surgical anastomosis. The nonbrittle sugar‐based stent holds the vessels together during the procedure and are dissolved upon the restoration of the blood flow. The incorporation of sodium citrate minimizes the chance of thrombosis. The dissolution rate and the mechanical properties of the sugar‐based stent can be tailored between 4 and 8 min. To enable the fabrication of stents with desirable geometries and dimensions, 3D printing is utilized to fabricate the stents. The effectiveness of the printed sugar‐based stent is assessed ex vivo. The fabrication procedure is fast and can be performed in the operating room.
David Oliver: Clinical records, plain English, and professional terminology
Authors: David Oliver
Journal: BMJ (2018)

In 2014 the award winning author John Lanchester argued in his book How to Speak Money 1 that the global financial crash had occurred partly because most of us have little understanding of finance, especially of its professional terminology and jargon. But he also acknowledged that, while jargon can be lazily or deliberately obfuscating and can exclude the public, it can also provide precise, succinct shorthand that’s much harder to explain in plain English.

Among his glossary were “derivatives markets,” “consumer surplus,” “short selling,” “Laffer curve,” and “VIX index.” Search these online, and they require lengthy explanations in plain English, with further definitions of the terms used to describe them. For instance, a derivative is “a contract that derives its value …
Venetoclax with azacitidine disrupts energy metabolism and targets leukemia stem cells in patients with acute myeloid leukemia
Authors: Daniel A. Pollyea, Brett M. Stevens, Courtney L. Jones, Amanda Winters, Shanshan Pei, Mohammad Minhajuddin, Angelo D’Alessandro, Rachel Culp-Hill, Kent A. Riemondy, Austin E. Gillen, Jay R. Hesselberth, Diana Abbott, Derek Schatz, Jonathan A. Gutman, Enkhtsetseg Purev, Clayton Smith, Craig T. Jordan
Journal: Nature Medicine (2018)
The Novel SYK/JAK Inhibitor Cerdulatinib Demonstrates Good Tolerability and Clinical Response in a Phase 2a Study in Relapsed/Refractory Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma
Authors: Steven M. Horwitz, Tatyana A. Feldman, Brian T. Hess, Michael S Khodadoust, Youn H. Kim, Javier Munoz, Manish R Patel, Tycel J. Phillips, Stephen D. Smith, Sonali M. Smith, Ryan A. Wilcox, Andrew Steele, Anjali Pandey, Matt R Birrell, Janet M. Leeds, Pamela B. Conley, Glenn Michelson, Gregory P. Coffey, John T Curnutte, Paul A. Hamlin
Journal: Blood (2018)
Analysis of 1135 gut metagenomes identifies sex-specific resistome profiles
Authors: Trishla Sinha, Arnau Vich Vila, Sanzhima Garmaeva, Soesma A. Jankipersadsing, Floris Imhann, Valerie Collij, Marc Jan Bonder, Xiaofang Jiang, Thomas Gurry, Eric J. Alm, Mauro D’Amato, Rinse K. Weersma, Sicco Scherjon, Cisca Wijmenga, Jingyuan Fu, Alexander Kurilshikov, Alexandra Zhernakova
Journal: Gut Microbes (2018)

Several gastrointestinal diseases show a sex imbalance, although the underlying (patho)physiological mechanisms behind this are not well understood. The gut microbiome may be involved in this process, forming a complex interaction with host immune system, sex hormones, medication and other environmental factors. Here we performed sex-specific analyses of fecal microbiota composition in 1135 individuals from a population-based cohort. The overall gut microbiome composition of females and males was significantly different (p = 0.001), with females showing a greater microbial diversity (p = 0.009). After correcting for the effects of intrinsic factors, smoking, diet and medications, female hormonal factors such as the use of oral contraceptives and undergoing an ovariectomy were associated with microbial species and pathways. Females had a higher richness of antibiotic-resistance genes, with the most notable being resistance to the lincosamide nucleotidyltransferase (LNU) gene family. The higher abundance of resistance genes is consistent with the greater prescription of the Macrolide-Lincosamide-Streptogramin classes of antibiotics to females. Furthermore, we observed an increased resistance to aminoglycosides in females with self-reported irritable bowel syndrome. These results throw light upon the effects of common medications that are differentially prescribed between sexes and highlight the importance of sex-specific analysis when studying the gut microbiome and resistome.
Phase I study of 4-bromothenylguanine (4-BTG, PaTrin 2), an alkyltransferase inactivator, and temozolomide.
Authors: Middleton, M Ranson, SM Lee, J Bridgewater, RS McElhinney, Tbh McMurry, N Thatcher, G Halbert, S Armstrong, GP Margison
Journal: Clinical Cancer Research (2000)
Development of an Accurate and Proactive Immunomodulatory Strategy to Improve Bone Substitute Material-Mediated Osteogenesis and Angiogenesis
Authors: Zhi-wei Zheng, Ya-hong Chen, Ding-yu Wu, Jin-bing Wang, Ming-ming Lv, Xian-song Wang, Jian Sun, Zhi-Yong Zhang
Journal: Theranostics (2018)

Background: Treatment of large bone defects represents a major clinical problem worldwide.Suitable bone substitute materials are commonly required to achieve successful bone regeneration, and much effort has been spent to optimize their chemical compositions, 3D architecture and mechanical properties.However, material-immune system interactions are increasingly being recognized as a crucial factor influencing regeneration.Here, we envisioned an accurate and proactive immunomodulation strategy via delivery of IL-4 (key regulator of macrophage polarization) to promote bone substitute material-mediated regeneration.Methods: Four different IL-4 doses (0 ng, 10 ng, 50 ng and 100 ng) were delivered into rat large cranial bone defects at day 3 post-operation of decellularized bone matrix (DBM) material implantation, and the osteogenesis, angiogenesis and macrophage polarization were meticulously evaluated.Results: Micro-CT analysis showed that immunomodulation with 10 ng IL-4 significantly outperformed the other groups in terms of new bone formation (1.23-5.05fold) and vascularization (1.29-6.08 fold), achieving successful defect bridging and good vascularization at 12 weeks.Histological analysis at 7 and 14 days showed that the 10 ng group generated the most preferable M1/M2 macrophage polarization profile, resulting in a pro-healing microenvironment with more IL-10 and less TNF-α secretion, a reduced apoptosis level in tissues around the materials, and enhanced mesenchymal stem cell migration and osteogenic differentiation.Moreover, in vitro studies revealed that M1 macrophages facilitated mesenchymal stem cell migration, while M2 macrophages significantly increased cell survival, proliferation and osteogenic differentiation, explaining the in vivo findings.Conclusions: Accurate immunomodulation via IL4 delivery significantly enhanced DBM-mediated osteogenesis and angiogenesis via the coordinated involvement of M1 and M2 macrophages, revealing the promise of this accurate and proactive immunomodulatory strategy for developing new bone substitute materials.
Neonatal Heart Regeneration
Authors: Nicholas T. Lam, Hesham A. Sadek
Journal: Circulation (2018)

Background: The adult mammalian heart is incapable of meaningful functional recovery after injury, and thus promoting heart regeneration is 1 of the most important therapeutic targets in cardiovascular medicine. In contrast to the adult mammalian heart, the neonatal mammalian heart is capable of regeneration after various types of injury. Since the first report in 2011, a number of groups have reported their findings on neonatal heart regeneration. The current review provides a comprehensive analysis of heart regeneration studies in neonatal mammals conducted to date, outlines lessons learned, and poses unanswered questions. Methods: We performed a PubMed search using the keywords “neonatal” and “heart” and “regeneration.” In addition, we assessed all publications that cited the first neonatal heart regeneration reports: Porrello et al, Science , Feb 2011 for apical resection injury; Porrello et al, PNAS , Dec 2012 for coronary ligation injury; and Mahmoud et al, Nature Methods , Jan 2014 for surgical methodology. Publications were examined for surgical models used, timing of surgery, and postinjury assessment including anatomic, histological, and functional assessment, as well as conclusions drawn. Results: We found 30 publications that performed neonatal apical resection, 19 publications that performed neonatal myocardial infarction by coronary artery ligation, and 6 publications that performed cryoinjury using liquid nitrogen–cooled metal probes. Both apical resection and ischemic infarction injury in neonatal mice result in a robust regenerative response, mediated by cardiomyocyte proliferation. On the other hand, several reports have demonstrated that cryoinjury is associated with incomplete heart regeneration in neonatal mice. Not surprisingly, several studies suggest that injury size, as well as surgical and histological techniques, can strongly influence the observed regenerative response and final conclusions. Studies have utilized these neonatal cardiac injury models to identify factors that either inhibit or stimulate heart regeneration. Conclusions: Overall, there is consensus that both apical resection and coronary ligation injuries during the first 2 days of life result in heart regeneration in neonatal mammals, whereas cryoinjury was not associated with a similar regenerative response. This regenerative response is mediated by proliferation of preexisting cardiomyocytes, and is modifiable by injury size and surgical technique, as well as metabolic, immunologic, genetic, and environmental factors.
Multiprotein Complex With TRPC (Transient Receptor Potential-Canonical) Channel, PDE1C (Phosphodiesterase 1C), and A2R (Adenosine A2 Receptor) Plays a Critical Role in Regulating Cardiomyocyte cAMP and Survival
Authors: Yishuai Zhang, Walter Knight, Si Chen, Amy Mohan, Chen Yan
Journal: Circulation (2018)

cAMP plays a critical role in regulating cardiomyocyte survival. Various cAMP signaling pathways behave distinctly or in opposition. We have previously reported that activation of cAMP hydrolysis by cyclic nucleotide phosphodiesterase 1C (PDE1C) promotes cardiomyocytes death/apoptosis, yet the underlying molecular mechanism remains unknown. In this study, we aimed to identify the specific cAMP signaling pathway modulated by PDE1C and determine the mechanism by which Ca2+/calmodulin-stimulated PDE1C is activated.To study cardiomyocyte death/apoptosis, we used both isolated mouse adult cardiomyocytes in vitro and doxorubicin-induced cardiotoxicity in vivo. We used a variety of pharmacological activators and inhibitors as well as genetically engineered molecular tools to manipulate the expression and activity of proteins of interest.We found that the protective effect of PDE1C inhibition/deficiency on Ang II or doxorubicin-induced cardiomyocyte death/apoptosis is dependent on cAMP-generating adenosine A2 receptors (A2Rs), suggesting that PDE1C's cAMP-hydrolyzing activity selectively modulates A2R-cAMP signaling in cardiomyocytes. In addition, we found that the effects of PDE1C activation on Ang II-mediated cAMP reduction and cardiomyocyte death are dependent on transient receptor potential-canonical (TRPC) channels, in particular TRPC3. We also observed synergistic protective effects on cardiomyocyte survival from the combination of A2R stimulation together with PDE1 or TRPC inhibition. Coimmunostaining and coimmunoprecipitation studies showed that PDE1C is localized in proximity with A2R and TRPC3 in the plasma membrane and perhaps T tubules. It is important to note that we found that doxorubicin-induced cardiac toxicity and dysfunction in mice are attenuated by the PDE1 inhibitor IC86340 or in PDE1C knockout mice, and this protective effect is significantly diminished by A2R antagonism.We have characterized a novel multiprotein complex comprised of A2R, PDE1C, and TRPC3, in which PDE1C is activated by TRPC3-derived Ca2+, thereby antagonizing A2R-cAMP signaling and promoting cardiomyocyte death/apoptosis. Targeting these molecules individually or in combination may represent a compelling therapeutic strategy for potentiating cardiomyocyte survival.
A Multicentre Evaluation of the Role of the Prostate Health Index (PHI) in Regions with Differing Prevalence of Prostate Cancer: Adjustment of PHI Reference Ranges is Needed for European and Asian Settings
Authors: Peter K.-F. Chiu, Chi-Fai Ng, Axel Semjonow, Yao Zhu, Sébastien Vincendeau, Alain Houlgatte, Massimo Lazzeri, Giorgio Guazzoni, Carsten Stephan, Alexander Haese, Ilse Bruijne, Jeremy Yuen-Chun Teoh, Chi Ho Leung, Paola Casale, Chih Hung Chiang, Lincoln Guan-Lim Tan, Edmund Chiong, Chao Yuan Huang, Hsi Chin Wu, Daan Nieboer, Ding-Wei Ye, Chris H. Bangma, Monique J. Roobol
Journal: European Urology (2018)
Variants of<scp>CARD</scp>14 are predisposing factors for generalized pustular psoriasis (<scp>GPP</scp>) with psoriasis vulgaris but not for<scp>GPP</scp>alone in a Chinese population
Authors: L. Li, J. You, X. Fu, Z. Wang, Y. Sun, H. Liu, F. Zhang
Journal: British Journal of Dermatology (2018)
Comparison of the Prognostic Utility of the Cell Cycle Progression Score for Predicting Clinical Outcomes in African American and Non-African American Men with Localized Prostate Cancer
Authors: Daniel J. Canter, Julia Reid, Maria Latsis, Margaret Variano, Shams Halat, Saradha Rajamani, Kristen E. Gurtner, Zaina Sangale, Michael Brawer, Steven Stone, Stephen Bardot
Journal: European Urology (2018)

Better prostate cancer risk stratification is necessary to inform medical management, especially for African American (AA) men, for whom outcomes are particularly uncertain. To evaluate the utility of both a cell cycle progression (CCP) score and a clinical cell-cycle risk (CCR) score to predict clinical outcomes in a large cohort of men with prostate cancer highly enriched in an AA patient population. Patients were diagnosed with clinically localized adenocarcinoma of the prostate and treated at The Ochsner Clinic (New Orleans, LA, USA) from January 2006 to December 2011. CCP scores were derived from archival formalin-fixed, paraffin-embedded biopsy tissue. CCR scores were calculated as the combination of molecular (CCP score) and clinical (Cancer of the Prostate Risk Assessment [CAPRA] score) components. Active treatment (radical prostatectomy, radiation therapy alone, or radiation and hormone therapy) or watchful waiting. The primary outcome was progression to metastatic disease. Association with outcomes was evaluated via Cox proportional hazards survival analysis and likelihood ratio tests. The final cohort included 767 men, of whom 281 (36.6%) were AA. After accounting for ancestry, treatment, and CAPRA in multivariable analysis, the CCP score remained a significant predictor of metastatic disease (hazard ratio [HR] 2.04; p < 0.001), and there was no interaction with ancestry (p = 0.20) or treatment (p = 0.09). The CCR score was highly prognostic (HR 3.86; p < 0.001), and as with the CCP score, there was no interaction with ancestry (p = 0.24) or treatment (p = 0.32). Limitations include the retrospective study design and the use of self-reported ancestry information. A CCR score provided significant prognostic information regardless of ancestry. The findings demonstrate that AA men in this study cohort appear to have similar prostate cancer outcomes to non-AA patients after accounting for all available molecular and clinicopathologic variables. In this study we evaluated the ability of a combined molecular and clinical score to predict the progression of localized prostate cancer. We found that the combined molecular and clinical score predicted progression to metastasis regardless of patient ancestry or treatment. This suggests that the combined molecular and clinical score may be a valuable tool for determining the risk of metastasis in men with newly diagnosed prostate cancer in order to make appropriate treatment decisions.
Phase 2/3 Trial of Subcutaneously Administered Marzeptacog Alfa (activated) an Engineered FVIIa in Hemophilia with Inhibitors - Pharmacokinetics, Pharmacodynamics, Safety and Efficacy
Authors: Howard Levy, Levani Makhaldiani, Genadi Iosava, Johnny Mahlangu, Marina V Kosinova, Heghine Khacchatryan, Frank Del Greco, Frank V. McL. Booth
Journal: Blood (2018)
Interleukin‐17A Inhibition Diminishes Inflammation and New Bone Formation in Experimental Spondyloarthritis
Authors: Melissa N. van Tok, Leonie M. van Duivenvoorde, Ina Kramer, Peter Ingold, Sabina Pfister, Lukas Roth, Iris C. Blijdorp, Marleen G. H. van de Sande, Joel D. Taurog, Frank Kolbinger, Dominique L. Baeten
Journal: Arthritis & Rheumatology (2018)

It remains unclear if and how inflammation and new bone formation in spondyloarthritis (SpA) are coupled. We undertook this study to assess the hypothesis that interleukin-17A (IL-17A) is a pivotal driver of both processes.The effect of tumor necrosis factor (TNF) and IL-17A on osteogenesis was tested in an osteoblastic differentiation assay using SpA fibroblast-like synoviocytes (FLS) differentiated with dexamethasone, β-glycophosphatase, and ascorbic acid. IL-17A blockade was performed in HLA-B27/human β2 -microglobulin (hβ2 m)-transgenic rats, which served as a model for SpA in both prophylactic and therapeutic settings. Inflammation and new bone formation were evaluated by micro-computed tomography imaging, histologic analysis, and gene expression profiling.TNF and IL-17A significantly increased in vitro osteoblastic differentiation. In vivo, prophylactic blockade of IL-17A significantly delayed spondylitis and arthritis development and decreased arthritis severity. Anti-IL-17A treatment was also associated with prevention of bone loss and periosteal new bone formation. Therapeutic targeting of IL-17A after the initial inflammatory insult also significantly reduced axial and peripheral joint inflammation. This treatment was again associated with a marked reduction in spinal and peripheral structural damage, including new bone formation. RNA sequencing of target tissue confirmed that IL-17A is a key driver of the molecular signature of disease in this model and that therapeutic anti-IL-17A treatment reversed the inflammatory signature and the selected gene expression related to bone damage.Both prophylactic and therapeutic inhibition of IL-17A diminished inflammation and new bone formation in HLA-B27/hβ2 m-transgenic rats. Taken together with the ability of IL-17A to promote osteoblastic differentiation of human SpA FLS, these data suggest a direct link between IL-17A-driven inflammation and pathologic new bone formation in SpA.
Abstract 16835: Effects of Polyethylene Glycol-20K on Postresuscitation Myocardial Function in a Rat Model of Cardiopulmonary Resuscitation
Authors: Qinyue Guo, Jin Yang, Changqing Miao, Weiping Huang, Zhangle Hu, Xiaobo Wu, Jennifer Bradley, Mary Ann Peberdy, Joseph P Ornato, Martin Mangino, Wanchun Tang
Journal: Circulation (2017)

Introduction: Polyethylene Glycol-20K (PEG-20K) is a hybrid cell impermeant that produces non-energy dependent water transfer in the microcirculation and improves microcirculatory flow (MF) during ...
Abstract 14695: Higher Beta Blocker Dose versus Lower Heart Rate in HFrEF With Atrial Fibrillation
Authors: Tarek Ajam, Samer Ajam, Srikant Devaraj, Masoor Kamalesh
Journal: Circulation (2017)

Background: The relative importance of the dose of beta blocker used as compared to the decrease in heart rate(HR) achieved remains unclear for patients with heart failure with reduced ejection fra...
Abstract 17361: A Very Unusual Case of ST Segment Elevation Myocardial Infarction Caused by Invasive Lymphoma
Authors: Muhammad W Choudhry, Hussain Ibrahim, Tarek Abu Sharifeh, Luba Frank, Mark Sides, Rafic Berbarie
Journal: Circulation (2017)

Background: STEMI is a life threatening condition that results from abrupt coronary artery occlusion resulting in trans-mural myocardial injury. Most common causes of STEMI include erosion of vulne...
Abstract 015: Critical Periods in Cardiovascular Health Across the Life Course: A Pooled Cohort Analysis
Authors: Norrina B Allen, Amy Krefman, Darwin Labarthe, Philip Greenland, Markus Juonala, Mika Kähönen, S. Rena Day, Terho Lehtimäki, Linda Van Horn, Lydia Bazzano, Lei Liu, Camilo F Alonso, Larry S Webber, Katja Pahkala, Tomi Laitinen, Olli Raitakari, Donald Lloyd-Jones
Journal: Circulation (2018)

Background: The prevalence of Ideal Cardiovascular Health (CVH) decreases with age, beginning in childhood. However, more precise estimates of trajectories of CVH across the lifespan are needed to guide intervention. The aims of this analysis are to describe trajectories in CVH from childhood through middle age and examine whether there are critical inflection points in the decline in CVH. Methods: We pooled data from five prospective childhood/early adulthood cohorts including Bogalusa, Young Finns, HB!, CARDIA, and STRIP. Clinical CVH factors—blood pressure, BMI, cholesterol, glucose—were categorized as poor, intermediate and ideal then summed to create a clinical CVH score, ranging from 0 to 8 (higher score= more ideal CVH). The association between clinical CVH score and age in years was modeled using a segmented linear mixed model, with a random participant intercept, fixed slopes, and fixed change points. Change points were estimated using an extension of the R package ‘segmented’ which utilizes a likelihood based approach to iteratively determine one or more change points. All models were adjusted for race, gender and cohort. Results: This study included 18,290 participants (51% female, 67% White, 46% between the ages of 8-11 at baseline). CVH scores decline with age from 8 through 55 years. We found two ages at which the slope of the CVH trajectories change significantly. CVH scores are generally stable from age 8 until the first change point at age 17 (95% CI 16.3-17.4), when they begin to decline more rapidly with a 0.08 CVH unit loss per year from age 17 to 30. The second change point occurs at age 30 (26.7-33.6) when the rate of decline increases by an additional 0.01 units per year. Conclusion: The clinical CVH score declines from favorable levels from childhood through adulthood, with a rapid decline starting at age 17 that becomes slightly steeper from age 30 to 55 years. These inflection points signal that there are critical periods in an individual’s clinical CVH trajectory during which prevention efforts may be targeted.