tbuckley/cabot-search huggingface dataset:
Abstract 15053: Hypoxic Preconditioning Improves the Effectiveness of Bone Marrow Mesenchymal Stem Cells for Cardiac Repair in Cynomolgus Monkeys With Myocardial Infarction
Authors: Xin Yang Hu, Yinchuan Xu, Yan Wu, Jing Zhao, Zhiwei Zhong, Lihong Chen, Jing Jin, Rongrong Wu, Qingju Li, Yingchao Wang, Haifeng Cheng, Minjian Kong, Fengjiang Zhang, Qi Chen, Chen Wang, Hongwei Zhan, Youqi Fan, Lei Yu, Qian Yang, Jianzhong Sun, Qian Li, Jie Liang, Wei Zhu, Jinghai Chen, Hong Yu, Jianyi Zhang, Jian’an Wang
Journal: Circulation (2015)

Background: Experiments in rodents have shown that hypoxic preconditioning (HP) can increase the therapeutic effectiveness of transplanted bone-marrow mesenchymal stem cells (MSCs) for myocardial infarction (MI). Here, we investigated whether the benefits associated with HP-MSC transplantation are also observed in non-human primates with MI. Methods: Allogeneic MSCs engineered to express GFP via lentiviral transfection were cultured in 21% oxygen (N-MSCs) or in 0.5% oxygen (HP-MSCs) for 24 hours. MI was surgically induced in Cynomolgus monkeys by ligating the left anterior-descending coronary artery distal to the first diagonal branch. 30 minutes later, 28 monkeys were each treated with 10 million MSCs intramyocardially injection. (N-MSCs: 13 monkeys; HP-MSCs: 15 monkeys). 11 additional monkeys treated with saline were served as control. LVEF and infarct sizes (IS) were measured echocardiographically, and the change in each parameter (ΔLVEF, ΔIS) was calculated by subtracting measurements taken 3 days post MI from measurements taken 28 days post MI. Incidents of ventricular arrhythmia were continuously detected via telemetry. Vascularity, arteriole density, proliferation, and endogenous progenitor-cell activation were evaluated via immunofluorescent assessments of CD31, SMA, Ki67, and c-kit expression, respectively; Engraftment was evaluated via RT-PCR measurements of GFP expression. Apoptosis was assessed with TUNEL staining, and the expression of pro-survival and/or pro-angiogenic genes was evaluated via immunoblot. Results: HP increased the expression of several pro-survival/pro-angiogenic factors (Ang 1, EPO, HGF, PDGF-BB) in cultured MSCs, and treatment with HP-MSCs, but not with N-MSCs was associated with significant improvements in ΔLVEF, ΔIS, vascularity, proliferation, and apoptosis. Vascularity and proliferation were also greater in HP-MSC animals than in N-MSC animals, and HP improved measurements of cell engraftment at Day 3, but not at Day 28. The incidence of arrhythmia (PVCs or NSVT) in all three experimental groups was similar. Conclusions: HP improved the effectiveness of MSC transplantation for the treatment of MI in non-human primates without increasing the occurrence of arrhythmogenic complications.
银屑病中 DLQI 新评分公式的提议
Authors: F. Rencz, L. Gulácsi, M. Péntek, A. K. Poór, M. Sárdy, P. Holló, A. Szegedi, É. Remenyik, V. Brodszky
Journal: British Journal of Dermatology (2018)

银屑病是一种常见慢性皮肤病, 大约2%的人群受此病影响。银屑病会对患者的日常活动和健康造成负面影响。皮肤生活质量指数 (DLQI) 是一种广泛使用的评估银屑病患者生活质量的指标。它包括 10 个问题, 涵盖症状和感受、日常活动、娱乐、工作和学习、个人关系和治疗。每个问题的评分如下: “完全没有”=0, “有一点”=1, “有些”=2 和“非常”=3。但是, 某些 DLQI 问题, 如运动、性困难和工作/学习并非与所有患者相关。由于“不相关”的回答被视为对患者生活无任何影响的问卷项(=0),它们可能使患者的生活质量评分出现假的改善。对于这些患者, 尽管患有重度银屑病, 他们更难符合临床指南要求成为更强效系统性治疗 (如生物制剂) 候选者的 DLQI 门槛。这项来自匈牙利的研究涉及 242 名银屑病患者。作者们开发了一种称为DLQI‐R的 DLQI 问卷新评分, 这种方法纠正了“不相关”回答选项中的偏倚, 并提供了它的效度 (即问卷的有效性)。DLQI‐R评分公式消除了标记为“不相关”的项目, 同时增加了相关项目在问卷总分中的权重。它主要是努力为那些单纯因为问卷中某些项目与他们不相关而不能符合治疗指南中 DLQI 标准的银屑病患者提供系统治疗的机会。 Linked Article:Rencz et al. Br J Dermatol 2018; 179:1102–1108
Management of Primary Lymph Nodal Gastrinoma With Liver Metastases Resulting in Zollinger-Ellison Syndrome
Authors: Deepa Singh, Sadhna B. Lal, Ashwani Sood, Rajesh Gupta, Rajender Kumar, Rakesh K. Vashishta, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2018)

Primary lymph node gastrinoma has been defined as gastrin-producing tumor present in lymph nodes and predominantly found in well-defined anatomical region known as gastrinoma triangle. They are usually localized preoperatively with imaging, and their surgical resection results in long-term relief. The authors report a case of unresectable primary lymph nodal gastrinoma with liver metastases in a 14-year-old adolescent boy with proven histopathology detected on Ga-DOTANOC whole-body PET/CT scan followed by preoperative multiple Lu-DOTATATE cycles for cytoreduction. Subsequent surgical resection of residual mass resulted in complete response with a follow-up of around 4 years in this unusual case of Zollinger-Ellison syndrome.
Glucose metabolism in patients with psoriasis
Authors: N.U. Friis, N. Hoffmann, M. Gyldenløve, L. Skov, T. Vilsbøll, F.K. Knop, H. Storgaard
Journal: British Journal of Dermatology (2018)

Background Epidemiological studies strongly suggest that psoriasis predisposes to type 2 diabetes. Several theories have been proposed to explain how these disease entities might be pathophysiologically connected. Objectives Our primary objective was to elucidate whether clinical data support the notion of common pathophysiological denominators in patients with psoriasis and type 2 diabetes, and thus to delineate the association between the two conditions that has arisen on the basis of epidemiological studies. Methods We reviewed clinical studies investigating parameters of glucose metabolism in patients with psoriasis. The PubMed and Embase databases were searched for studies investigating glucose metabolism in adult patients with psoriasis as a primary or secondary end point. Studies had to include a relevant control group. Results Twenty-six clinical studies reporting on insulin resistance, glucose tolerance or insulin secretion were eligible for review. The results were widely conflicting, with less than half of the studies showing results suggestive of defective glucose metabolism in patients with psoriasis. In general, the studies suffered from a lack of information regarding possible confounders and patient characteristics. Furthermore, the research methods varied, and in all but one study they might not have been appropriate to detect early and subtle defects in glucose metabolism. Conclusions The available literature does not unequivocally support common pathophysiological denominators in psoriasis and type 2 diabetes. Well-designed clinical studies are needed to expose potential diabetogenic defects in the glucose metabolism in patients with psoriasis.
Cooccurring JAK2 V617F and R1063H mutations increase JAK2 signaling and neutrophilia in myeloproliferative neoplasms
Authors: Cristina Mambet, Olga Babosova, Jean-Philippe Defour, Emilie Leroy, Laura Necula, Oana Stanca, Aurelia Tatic, Nicoleta Berbec, Daniel Coriu, Monika Belickova, Barbora Kralova, Lucie Lanikova, Jitka Vesela, Christian Pecquet, Pascale Saussoy, Violaine Havelange, Carmen C. Diaconu, Vladimir Divoky, Stefan N. Constantinescu
Journal: Blood (2018)
Clinical Outcomes Associated With Sickle Cell Trait
Authors: Rakhi P. Naik, Kim Smith-Whitley, Kathryn L. Hassell, Nkeiruka I. Umeh, Mariane de Montalembert, Puneet Sahota, Carlton Haywood, Jean Jenkins, Michele A. Lloyd-Puryear, Clinton H. Joiner, Vence L. Bonham, Gregory J. Kato
Journal: Annals of Internal Medicine (2018)

Although sickle cell trait (SCT) is largely a benign carrier state, it may increase risk for certain clinical outcomes.
Response to "Tumor cells in search for glutamate: an alternative explanation for increased invasiveness of IDH1 mutant gliomas"
Authors: A. Trister, J. Scott, R. Rockne, K. Yagle, S. K. Johnston, A. Hawkins-Daarud, A. Baldock, K. R. Swanson
Journal: Neuro-Oncology (2014)

We thank the authors for a very thoughtful letter and agree that there are a number of different mechanisms through which isocitrate dehydrogenase (IDH) mutation, the downstream 2-hydroxyglutarate (2HG), can lead to a number of different state changes within tumor cells. The acidification of the tumor microenvironment was solely an interpretation of our mathematical model. It is much more likely that the effects are multifactorial, as mentioned by the authors, and the potential for a glutamate gradient resulting in diffusion behavior is an intriguing possibility that can easily be experimentally validated in vitro, though a more mechanistic explanation would be favored. It is possible that 2HG, and specifically the enantiomer R-2-hydroxyglutarate, which is formed by the conserved mutation at R132, may in fact inhibit 2-oxoglutarate–dependent dioxygenase activity, which in turn alters the stability of hypoxia-inducible factor alpha, leading to many larger downstream effects. We also agree that the authors' suggestion of a means of testing the hypothesis of glutamate depletion by using glutamate dehydrogenase inhibitors is a good one, and one that they are clearly well prepared to carry out.

The scope of our manuscript was to focus on the very evident difference in measurable tumor behavior in vivo for patients with IDH1 mutation, though we believe that the discussions about the molecular mechanism underlying this gross behavior is incredibly important to gain further understanding of the tumorigenicity of both low- and high-grade gliomas. We look forward to further discussion and data regarding the underlying mechanisms related to IDH mutation.
Abstract 15784: Impact of SLCO1B1 Genotype on Pediatric Simvastatin Pharmacokinetics
Authors: Jonathan Wagner, Susan Abdel-Rahman, Leon van Haandel, Andrea Gaedigk, Roger Gaedigk, Geetha Raghuveer, Ralph Kauffman, J. S Leeder
Journal: Circulation (2016)

Background: Simvastatin (SV) is administered as a lactone prodrug requiring hydrolysis to its active moiety, simvastatin acid (SA), to disrupt hepatic cholesterol biosynthesis. In adults, allelic v...
Obliterative Portal Venopathy Without Cirrhosis Is Prevalent in Pediatric Cystic Fibrosis Liver Disease With Portal Hypertension
Authors: Hao Wu, Megan Vu, Sadhna Dhingra, Ruth Ackah, John A. Goss, Abbas Rana, Norma Quintanilla, Kalyani Patel, Daniel H. Leung
Journal: Clinical Gastroenterology and Hepatology (2018)
Abstract 15077: Bilateral Inflammation in Carotid Arteries in Patients With Coronary Artery Disease is Associated With Increased Rate of Cardiovascular Events
Authors: Georgios Benetos, Konstantinos Toutouzas, Maria Drakopoulou, Fotini Mitropoulou, Angelos Papanikoloau, Andreas Synetos, Haralampos Grassos, Dimitrios Tousoulis, Elias Siores, Christodoulos Stefanadis
Journal: Circulation (2014)

Background: The prognostic role of both local and systemic inflammation in coronary artery disease (CAD) remains controversial. Microwave radiometry (MWR) is a new noninvasive method, which allows ...
Lethal Fentanyl and Cocaine Intoxication
Authors: Utsha G Khatri, Kendra Viner, Jeanmarie Perrone
Journal: New England Journal of Medicine (2018)

Lethal Fentanyl and Cocaine Intoxication In Philadelphia, 18 patients who had not used opioids previously presented over a 4-day period with severe opioid intoxication after smoking “crack” cocaine...
Avoidable Blood Transfusions
Authors: Antonio V. Sterpetti
Journal: JAMA Surgery (2018)

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Idarucizumab for Dabigatran Reversal in the Management of Patients With Gastrointestinal Bleeding
Authors: Sake J. Van der Wall, Renato D. Lopes, James Aisenberg, Paul Reilly, Joanne van Ryn, Stephan Glund, Amelie Elsaesser, Frederikus A. Klok, Charles V. Pollack, Menno V. Huisman
Journal: Circulation (2019)

Background: Although dabigatran has a favorable risk-benefit profile compared with vitamin K antagonist therapy for venous thromboembolism and nonvalvular atrial fibrillation, major bleeding events, including gastrointestinal (GI) bleeding, may occur. Therefore, our aim was to provide insights into the efficacy and safety of idarucizumab for urgent dabigatran reversal in patients with major GI bleeding. Methods: Patients with uncontrollable GI bleeding requiring reversal were enrolled from June 2014 through July 2016 in the RE-VERSE AD study (Reversal of Dabigatran Anticoagulant Effect With Idarucizumab), a prospective, multicenter, open-label study of idarucizumab, and were followed up for 90 days for primary and secondary outcomes. Patients were to receive a 5-g dose of intravenous idarucizumab, administered as 2 bolus infusions of 2.5 g no more than 15 minutes apart. The primary end point was the maximum reversal of dabigatran anticoagulation within 4 hours after administration of idarucizumab as measured by the dabigatran-specific assays diluted thrombin time and ecarin clotting time. Further end points included investigator-reported bleeding cessation within the first 24 hours and incidence of rebleeding, thromboembolic events, or mortality. Results: GI bleeding occurred in 137 patients enrolled in RE-VERSE AD, of which 84% was adjudicated as major or life-threatening, 48 (35.0%) was upper GI tract in origin, 43 (31.4%) was lower GI in origin, and 46 (33.6%) was either both or unknown. Complete reversal of dabigatran was observed in 118 of 121 patients (97.5%) with an elevated diluted thrombin time at presentation and 95 of 131 patients (72.5%) with an elevated ecarin clotting time and was similar for upper and lower GI bleeding. Bleeding cessation within 24 hours was reported in 92 of 134 evaluable patients (68.7%) after a median duration of 2.4 hours (interquartile range, 2.0–3.9 hours). During the 90-day follow-up, 6 patients (4.4%) had a postreversal thromboembolic event, and 20 patients (14.6%) died. Conclusions: Idarucizumab showed a rapid and complete reversal of dabigatran activity in nearly all patients presenting with GI bleeding, facilitating emergency patient care without the additional presence of anticoagulation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02104947.
V-ATPases and osteoclasts: ambiguous future of V-ATPases inhibitors in osteoporosis
Authors: Xiaohong Duan, Shaoqing Yang, Lei Zhang, Tielin Yang
Journal: Theranostics (2018)

Vacuolar ATPases (V-ATPases) play a critical role in regulating extracellular acidification of osteoclasts and bone resorption.The deficiencies of subunit a3 and d2 of V-ATPases result in increased bone density in humans and mice.One of the traditional drug design strategies in treating osteoporosis is the use of subunit a3 inhibitor.Recent findings connect subunits H and G1 with decreased bone density.Given the controversial effects of ATPase subunits on bone density, there is a critical need to review the subunits of V-ATPase in osteoclasts and their functions in regulating osteoclasts and bone remodeling.In this review, we comprehensively address the following areas: information about all V-ATPase subunits and their isoforms; summary of V-ATPase subunits associated with human genetic diseases; V-ATPase subunits and osteopetrosis/osteoporosis; screening of all V-ATPase subunits variants in GEFOS data and in-house data; spectrum of V-ATPase subunits during osteoclastogenesis; direct and indirect roles of subunits of V-ATPases in osteoclasts; V-ATPase-associated signaling pathways in osteoclasts; interactions among V-ATPase subunits in osteoclasts; osteoclast-specific V-ATPase inhibitors; perspective of future inhibitors or activators targeting V-ATPase subunits in the treatment of osteoporosis.
Abstract 18653: Outcomes After Induction Immunosuppression in Heart Transplant Patients
Authors: Vishnu Ambur, Sharven Taghavi, Yuka Furuya, Senthil Jayarajan, Akira Shiose, Eros Leotta, Jesus Gomez-Abraham, Yoshiya Toyoda
Journal: Circulation (2015)

Introduction: Outcomes after induction immunosuppression in heart transplant patients have not been investigated since the heart allocation policy was changed in 2006. The optimal induction therapy continues to be controversial with many centers continuing to use none at all. We evaluated the outcomes after modern induction immunosuppression agents with the primary end points being survival and rejection. Methods: The United Network for Organ Sharing (UNOS) database was examined for all heart transplants from January 2006 to December 2012. Patients receiving induction therapy were compared to those receiving no induction agent. Additional subgroup analysis was performed on the induction group including those patients receiving either basiliximab (Simulect), thymoglobulin, or alemtuzumab (Campath). Kaplan Meier survival curves and multivariate cox regression analysis were utilized to evaluate outcomes. Results: Of the 14,210 heart transplants performed during this time period, 5905 (41%) received no induction while 8605 (59%) received induction therapy. Interestingly, the no induction group had a lower incidence of acute rejection (15.5% vs. 36.8%, p = 0.005). However, Kaplan Meier analysis revealed no difference in survival between the two cohorts (6.36 vs. 6.23 years; p = 0.59). On multivariate analysis, induction was not associated with a survival advantage (HR: 0.95; 0.88 - 1.03, p = 0.23). Subgroup analysis revealed that patients receiving Campath had the highest incidence of acute rejection (29.5% vs. 19.3% vs. 9.6%, p &lt; 0.0001) and highest panel reactive antibody (7.6 vs 4.3 vs. 4.9, p = 0.002) while those receiving thymoglobulin had the lowest. However, Simulect (HR: 1.08; 0.97 - 1.19, p = 0.16), Campath (HR: 0.87; 0.69 - 1.09, p = 0.22), and Thymoglobulin (HR: 0.94; 0.77 - 1.14, p = 0.50) did not provide a survival benefit on multivariate or Kaplan Meier analysis (6.26 vs. 5.59 vs. 6.26 years; p = 0.21). Conclusions: This analysis of induction agents on outcomes after heart transplantation since the change in allocation policy in 2006 shows that induction does not affect survival when compared to no induction. Furthermore, there is no difference in survival when comparing the three most commonly used agents: Simulect, Campath, and thymoglobulin.
CD16A-Specific Tetravalent Bispecific Immune Cell Engagers Potently Induce Antibody-Dependent Cellular Phagocytosis (ADCP) on Macrophages
Authors: Susanne Wingert, Uwe Reusch, Armin Beez, Jens Pahl, Adelheid Cerwenka, Joachim Koch, Martin Treder
Journal: Blood (2018)
Reply to Sanguankeo and Upala on “Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis”
Authors: Le Shi, Yan-Ping Bao, Si-Jing Chen, Meng-Ying Ma, Ying Han, Yu-Mei Wang, Jie Shi, Michael V. Vitiello, Lin Lu
Journal: Sleep Medicine Reviews (2018)
Abstract 16138: Clinical Predictors of Right Ventricular Myocardial Fibrosis in Patients With Repaired Tetralogy of Fallot
Authors: Takashi Kido, Takayoshi Ueno, Masaki Taira, Hideto Ozawa, Tomomitsu Kanaya, Naoki Okuda, Koichi Toda, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2017)

Introduction: The optimal timing of pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (TOF) in the setting of chronic volume overload and concomitant right ventricular...
Increased risk of depression in patients with lupus erythematosus
Authors: J.H. Hesselvig, A. Egeberg, K. Kofoed, G. Gislason, L. Dreyer
Journal: British Journal of Dermatology (2018)

Lupus is a chronic autoimmune disease, meaning the body's immune system works against the body instead of protecting it. Systemic lupus may not only involve the skin but also internal organs such as lungs, heart, and kidneys, and is potentially a fatal disease, whereas cutaneous lupus is mainly restricted to the skin. It affects women more often than men and symptoms usually first appear when patients are aged in their 30s. This study, from Denmark, investigated if patients with lupus (cutaneous or systemic) have increased risk of depression. By using the unique Danish nationwide registers, the authors found that patients diagnosed with systemic or cutaneous lupus both had a 2‐fold increased risk of a subsequent diagnosis of depression compared with the general population in Denmark. Likewise, the risk of severe depression was increased for patients with cutaneous or systemic lupus. On the other hand, the risk of self‐harm and death from suicide were not significantly increased in patients with lupus. Surprisingly, the risk of depression is of similar magnitude for patients with systemic lupus, a potentially fatal disease, as for patients with cutaneous lupus. This indicates that the involvement of the skin has the same important impact as the systemic disease on the patients’ mental health. It is relevant that both dermatologists and patients know about this significant increase in risk of depression.
ACR Practice Parameter for the Performance of Gallium-68 DOTATATE PET/CT for Neuroendocrine Tumors
Authors: Rathan M. Subramaniam, Marques L. Bradshaw, Kenneth Lewis, Daniella Pinho, Chirayu Shah, Ronald C. Walker
Journal: Clinical Nuclear Medicine (2018)

Radiopharmaceuticals targeting cell surface expression of somatostatin receptors (SSTRs) are particularly useful in the evaluation of neuroendocrine tumors. Gallium-68 DOTA-Tyr-octreotatate (Ga-DOTATATE) primarily binds to SSTR type 2 receptors. Ga DOTATATE PET/CT is proven to have high impact on the management of neuroendocrine patients compared to traditional anatomical imaging as well as provides additional information over that of conventional nuclear medicine studies (indium-III DTPA-octreotide). It can result in change in management of approximately 75% of patients with neuroendocrine tumors. Ga DOTATATE and F FDG PET/CT imaging are complementary, with the degree of uptake varying depending on the degree of differentiation of the tumor. Well-differentiated tumors maintain their SSTRs and are positive on Ga DOTATATE PET/CT scan, while dedifferentiated tumors are less likely to demonstrate uptake of Ga DOTATATE but will demonstrate uptake with F FDG PET/CT. In addition, Ga DOTATATE PET/CT identifies patients with SSTR expression in their tumors, who have progressed on somatostatin analog therapy, for treatment with Lu DOTATATE.
Macrophage Checkpoint Blockade in Cancer — Back to the Future
Authors: Alberto Mantovani, Dan L. Longo
Journal: New England Journal of Medicine (2018)

Macrophages are an essential component of the tumor microenvironment and have been ascribed a role in cancer-promoting inflammation.1,2 Phagocytic cells (a component of innate immunity) mediate first-line resistance against pathogens and, when appropriately activated, can mediate extracellular killing and phagocytosis of tumor cells.1-3 However, tumor progression is associated with subversion of immunity, and signals in the tumor microenvironment originating from cancer cells, stroma, and other immunocompetent cells set tumor-associated macrophages to a tumor-promoting mode (
Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3·6 million adults in the UK
Authors: Krishnan Bhaskaran, Isabel dos-Santos-Silva, David A Leon, Ian J Douglas, Liam Smeeth
Journal: The Lancet Diabetes & Endocrinology (2018)

BMI is known to be strongly associated with all-cause mortality, but few studies have been large enough to reliably examine associations between BMI and a comprehensive range of cause-specific mortality outcomes.