tbuckley/cabot-search huggingface dataset:
FRI0243 Sapho syndrome in hungary
Authors: É Koó, I Orbán, ZS Balogh, I Ujfalussy, K Imre, J Kelemen, ZS Tarján
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> SAPHO syndrome is an abbreviation according to the suggestion of Chamot (1990) from the words Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis. There are more than 50 synonyms in the first described SAPHO syndrome by Chamot, too. The usage of SAPHO syndrome diagnosis became widespread only in the latest years. <h3>Objectives</h3> Authors studied the Hungarian publications examining the appearance and extending of SAPHO syndrome in 1998. Chronic recurrent multifocal osteomyelitis (CRMO) diagnosis is used also nowadays in the paediatric cases corresponding to SAPHO syndrome. Authors give a review of the SAPHO syndrome cases publicated and/or presented in Hungary. <h3>Methods</h3> There were 8 cases as acne arthritis,1 case as SNSA,5 cases as SAPHO syndrome publicated,31 cases as sternoclavicular involvement in psoriatic arthritis,3 CRMO cases,1 SAPHO syndrome presented in Hungarian Congresses, together 49 case reports. <h3>Results</h3> The concomitant skin laesions were: acne conglobata, fulminans or psoriasis vulgaris. Mean age:33,3 (12–60). Male: female ratio was: 29/20. Almost all the patients had peripheral arthritis, most of them had sacroiliitis and/or SCC arthritis. <h3>Conclusion</h3>
Socioeconomic Influences on the Treatment and Outcomes of Patients with Acute Myeloid Leukemia: Experience from an Urban Academic Center
Authors: Jonathan Pan, Sushil Ghimire, Molly Halloran, Alexander Xu, Tingting Zhan, Gina Keiffer, Lindsay Wilde, Neil Palmisiano, Margaret Kasner, Adam F. Binder
Journal: Blood (2020)
OP0041 Esophageal manometry findings in patients with raynaud’s phenomenon and positive antinuclear antibodies
Authors: A Arteaga, E Trujillo, I Ferraz, A Alvarez-Pío, J Bethencourt, F Díaz-González, C Casanova, T González, S Bustabad
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To study the esophageal manometry in patients with Raynaud´s phenomenon and positive antinuclear antibodies (ANA) in the absence of esophageal, skin or internal organs manifestations. <h3>Methods</h3> 14 patients, 13 women and 1 man (46,8 mean age; 9–65 years) with mean evolution time of Raynaud´s henomenon of 5 years were included in this study. Nailfold capillary microscopy study, autoantibodies profile and esophageal manometry (Synetics Manometry Unid. Synetics neumocapillary Pump and Poligraph) were performed in all patients. The lower esophageal sphincter, esophageal body and upper esophageal sphincter pressures were analysed independently. <h3>Results</h3> 44% patients had a lower esophageal sphincter hipotonia which showed a significant relationship (p &lt; 0.05) with the presence of both articular disease (33.5%) and anti-centromere antibodies (44.4%). However, the naildfold scleroderma pattern (61%) did not show a significant relationship with lower esophageal sphincter hipotonia. 33.3% patients showed unspecific motor alterations in the esophageal body. There was significant relationship (p &lt; 0.001) between esophageal body alterations and the naildfold scleroderma pattern. In all patients studied, the function of the upper esophageal sphincter was within the normal limits. In the control group of patients with Raynaud´s phenomenon and negative ANA, the esophageal manometry was normal. <h3>Conclusion</h3> Alterations in the esophageal manometry are frequent in patients with Raynaud`s phenomenon and positive ANA and they suggest the presence of systemic disease even in the absence of skin or internal organs involvement.
Evaluation of a Pan-Lysyl Oxidase Inhibitor, Pxs-5505, in Myelofibrosis: A Phase I, Randomized, Placebo Controlled Double Blind Study in Healthy Adults
Authors: Joan How, Yiwen Liu, Jennifer Lombardi Story, Donna S. Neuberg, Katya Ravid, Wolfgang Jarolimek, Brett Charlton, Gabriela S. Hobbs
Journal: Blood (2020)
Chromatin Looping Shapes KLF5-Dependent Transcriptional Programs in Human Epithelial Cancers
Authors: Yanli Liu, Bingqian Guo, Estrella Aguilera-Jimenez, Vivian S. Chu, Jin Zhou, Zhong Wu, Joshua M. Francis, Xiaojun Yang, Peter S. Choi, Swneke D. Bailey, Xiaoyang Zhang
Journal: Cancer Research (2020)

Activation of transcription factors is a key driver event in cancer. We and others have recently reported that the Krüppel-like transcription factor KLF5 is activated in multiple epithelial cancer types including squamous cancer and gastrointestinal adenocarcinoma, yet the functional consequences and the underlying mechanisms of this activation remain largely unknown. Here we demonstrate that activation of KLF5 results in strongly selective KLF5 dependency for these cancer types. KLF5 bound lineage-specific regulatory elements and activated gene expression programs essential to cancer cells. HiChIP analysis revealed that multiple distal KLF5 binding events cluster and synergize to activate individual target genes. Immunoprecipitation-mass spectrometry assays showed that KLF5 interacts with other transcription factors such as TP63 and YAP1, as well as the CBP/EP300 acetyltransferase complex. Furthermore, KLF5 guided the CBP/EP300 complex to increase acetylation of H3K27, which in turn enhanced recruitment of the bromodomain protein BRD4 to chromatin. The 3D chromatin architecture aggregated KLF5-dependent BRD4 binding to activate polymerase II elongation at KLF5 target genes, which conferred a transcriptional vulnerability to proteolysis-targeting chimera-induced degradation of BRD4. Our study demonstrates that KLF5 plays an essential role in multiple epithelial cancers by activating cancer-related genes through 3D chromatin loops, providing an evidence-based rationale for targeting the KLF5 pathway. SIGNIFICANCE: An integrative 3D genomics methodology delineates mechanisms underlying the function of KLF5 in multiple epithelial cancers and suggests potential strategies to target cancers with aberrantly activated KLF5.
Genomic Architecture of Rapid Parallel Adaptation to Fresh Water in a Wild Fish
Authors: Shao-Bing Zong, Yu-Long Li, Jin-Xian Liu
Journal: Molecular Biology and Evolution (2020)

Abstract Rapid adaptation to novel environments may drive changes in genomic regions through natural selection. However, the genetic architecture underlying these adaptive changes is still poorly understood. Using population genomic approaches, we investigated the genomic architecture that underlies rapid parallel adaptation of Coilia nasus to fresh water by comparing four freshwater-resident populations with their ancestral anadromous population. Linkage disequilibrium network analysis and population genetic analyses revealed two putative large chromosome inversions on LG6 and LG22, which were enriched for outlier loci and exhibited parallel association with freshwater adaptation. Drastic frequency shifts and elevated genetic differentiation were observed for the two chromosome inversions among populations, suggesting that both inversions would undergo divergent selection between anadromous and resident ecotypes. Enrichment analysis of genes within chromosome inversions showed significant enrichment of genes involved in metabolic process, immunoregulation, growth, maturation, osmoregulation, and so forth, which probably underlay differences in morphology, physiology and behavior between the anadromous and freshwater-resident forms. The availability of beneficial standing genetic variation, large optimum shift between marine and freshwater habitats, and high efficiency of selection with large population size could lead to the observed rapid parallel adaptive genomic change. We propose that chromosomal inversions might have played an important role during the evolution of rapid parallel ecological divergence in the face of environmental heterogeneity in C. nasus. Our study provides insights into the genomic basis of rapid adaptation of complex traits in novel habitats and highlights the importance of structural genomic variants in analyses of ecological adaptation.
THU0251 Familial clustering of autoimmune diseases in sjÖgren’s syndrome: an italian case-control study
Authors: R Priori, F Conti, E Cassarà, E Medda, MA Stazi, C Tomassini, E Bozzolo, F Franceschini, T Urbano, R Giacomelli, G Valesini
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Autoimmune diseases often cluster in families. <h3>Objectives</h3> Aim of this study was to investigate the prevalence, the incidence and the risk for autoimmune diseases (AD) in first degree relatives (FDR) of italian Sjögren's syndrome (SS) patients. <h3>Methods</h3> A multicentre case-control study was performed in Italy. Cases (patients classified as SS according to 1994 EEC criteria) and controls (subjects without known history of autoimmune disorder) were randomly selected and interviewed by a trained medical doctor. Data on family history of AD in FDR were recorded. We calculated the incidence rate of AD in the two groups by dividing the number of cases of AD by person-years (py) at risk. The relative risk (RR) was estimated by dividing the incidence rate among relatives of cases by the incidence rate among relatives of controls. Furthermore we conducted stratified analyses according to sex of relatives and/or proband to evaluate whether the relation between SS in FDR and AD differs by sex. Statistical analyses were performed using STATA software. <h3>Results</h3> 143 SS cases and 140 controls were enrolled. 34/143 (23.8%) and 8/140 (5.7%) had at least one FDR with AD (p &lt; 0.01); 44/839 (5.24%) FDR of SS patients and 12/776 (1.55%) FDR of controls had AD (p &lt; 0.01). We estimated an incidence rate of 1.03 × 1000 py in SS group and 0.32 × 1000 py in control group. The ratio of incidence density showed that relatives of SS cases have three time probability to have an AD compared to relatives of controls (RR 3.24, CI 95% 1.71–6.14). We found that the risk for AD is epecially pronounced in relatives of female probands and it increases if the FDR is female, too. <h3>Conclusion</h3> This case-control study confirms the clustering of AD in SS families and defines the risk to have an AD for first degree relatives of patients with SS.
COVID-19-Associated Coagulopathy: Safety and Efficacy of Prophylactic Anticoagulation Therapy in Hospitalized Adults with COVID-19
Authors: Isaac Chambers, Sanjana Dayal, Patrick Ten Eyck, Alicia Eustes, Grerk Sutamtewagul, Lori Rosenstein, Steven R Bailey, Steven R. Lentz, Usha Perepu
Journal: Blood (2020)
Association of Echocardiographic Left Ventricular End-Systolic Volume and Volume-Derived Ejection Fraction With Outcome in Asymptomatic Chronic Aortic Regurgitation
Authors: Li-Tan Yang, Vidhu Anand, Elena I. Zambito, Patricia A. Pellikka, Christopher G. Scott, Prabin Thapa, Ratnasari Padang, Masaaki Takeuchi, Rick A. Nishimura, Maurice Enriquez-Sarano, Hector I. Michelena
Journal: JAMA Cardiology (2020)

Volumetric measurements by transthoracic echocardiogram may better reflect left ventricular (LV) remodeling than conventional linear LV dimensions. However, the association of LV volumes with mortality in patients with chronic hemodynamically significant aortic regurgitation (AR) is unknown.To assess whether LV volumes and volume-derived LV ejection fraction (Vol-LVEF) are determinants of mortality in AR.This cohort study included consecutive asymptomatic patients with chronic moderately severe to severe AR from a tertiary referral center (January 2004 through April 2019).Clinical and echocardiographic data were analyzed retrospectively. Aortic regurgitation severity was graded by comprehensive integrated approach. De novo disk-summation method was used to derive LV volumes and Vol-LVEF.Associations between all-cause mortality under medical surveillance and the following LV indexes: linear LV end-systolic dimension index (LVESDi), linear LVEF, LV end-systolic volume index (LVESVi), and Vol-LVEF.Of 492 asymptomatic patients (mean [SD] age, 60 [17] years; 425 men [86%]), ischemic heart disease prevalence was low (41 [9%]), and 453 (92.1%) had preserved linear LVEF (≥50%) with mean (SD) LVESVi of 41 (15) mL/m2. At a median (interquartile range) of 5.4 (2.5-10.1) years, 66 patients (13.4%) died under medical surveillance; overall survival was not different than the age- and sex-matched general population (P = .55). Separate multivariate models, adjusted for age, sex, Charlson Comorbidity Index, and AR severity, demonstrated that in addition to linear LVEF and LVESDi, LVESVi and Vol-LVEF were independently associated with mortality under surveillance (all P < .046) with similar C statistics (range, 0.83-0.84). Spline curves showed that continuous risks of death started to rise for both linear LVEF and Vol-LVEF less than 60%, LVESVi more than 40 to 45 mL/m2, and LVESDi above 21 to 22 mm/m2. As dichotomized variables, patients with LVESVi more than 45 mL/m2 exhibited increased relative death risk (hazard ratio, 1.93; 95% CI, 1.10-3.38; P = .02) while LVESDi more than 20 mm/m2 did not (P = .32). LVESVi more than 45 mL/m2 showed a decreased survival trend compared with expected population survival.In this large asymptomatic cohort of patients with hemodynamically significant AR, LVESVi and Vol-LVEF worked equally as well as LVESDi and linear LVEF in risk discriminating patients with excess mortality. A LVESVi threshold of 45 mL/m2 or greater was significantly associated with an increased mortality risk.
Outcomes in Patients with Hematologic Disease and COVID-19 in Russia: Interim Analysis of CHRONOS19 Registry
Authors: Olga A. Gavrilina, Kristina Zakurdaeva, Vladimir I. Vorobyev, Anastasia N. Vasileva, Lev S. Butaev, Alena Sukhareva, Lubov Gavrilova, Olga Samoylova, Maria Grishunina, Ochsana Ochirova, Alina Karpova, Olga Panteleeva, Mikhail A. Kunst, Vasily Shuvaev, Anzhelika Rakhmani, Tatiana V. Gaponova, Gennadiy M. Galstyan, Vera V. Troitskaya, Anton V. Luchkin, Elena N. Parovichnikova, Valery Savchenko
Journal: Blood (2020)
Patient Characteristics of Long-Term Responders to Mogamulizumab: Results from the MAVORIC Study
Authors: Youn H. Kim, Michael S. Khodadoust, Adele de Masson, Hélène Moins-Teisserenc, Takahiro Ito, Karen Dwyer, Fiona Herr, Martine Bagot
Journal: Blood (2020)
Association between treatment center experience and survival after diagnosis of stage I to III Merkel cell carcinoma treated with surgery with or without postoperative radiation therapy
Authors: Fallon E. Chipidza, Manisha Thakuria, Jonathan D. Schoenfeld, Ann W. Silk, Paul J. Catalano, Charles H. Yoon, Glenn J. Hanna, James A. DeCaprio, Roy B. Tishler, Danielle N. Margalit
Journal: Journal of the American Academy of Dermatology (2020)
Delivery of Fviii-mcoET3 to Previously Untreated Sheep Using Human Placental Cells Enables Durable Elevation of Plasma FVIII Levels and Avoids Inhibitor Formation
Authors: Brady Trevisan, Martin Rodriguez, Sunil George, Shannon Lankford, Jordan E Shields, Jorge Figueroa, Diane Meares, John Owen, Anthony Atala, Christopher B Doering, H. Trent Spencer, Christopher D Porada, M. Graca Almeida-Porada
Journal: Blood (2020)
Abstract 365: Ponatinib Triggers Cardiac Inflammation by STAT-3 Dependent Immune Checkpoint Blockade
Authors: Anand P Singh, Tousif Sultan, Prachi Umbarkar, Qinkun Zhang, Hind Lal
Journal: Circulation Research (2020)

Background: Ponatinib is a potent anticancer tyrosine kinase inhibitor (TKI) with considerable cardiotoxicity. The manifestation of cardiovascular adverse events, including fatal myocardial infarction and congestive heart failure, has hampered its clinical use. Therefore, a better understanding of the mechanism by which ponatinib exerts cardiotoxicity is urgently warranted to efficiently counteract treatment-related adversities. Methods: Wild type C57BL/6, comorbidity mouse model ApoE -/- , and pressure overload (PO) mouse model were used to investigate the cardiotoxic mechanism of ponatinib. Echocardiography was performed to assess cardiac function. Flow cytometry analysis was performed to assess the dynamics of inflammation. Results: We observed that high-fat diet (HFD) fed ApoE -/- mice develop cardiac dysfunction within 2 weeks of ponatinib treatment. An unbiased RNA-Seq analysis revealed significant upregulation of inflammatory genes (CCR1, CCR5, CCL6, CCL8, CCL9, CXCL4) in ponatinib treated hearts. Since ApoE -/- background, and HFD are known confounder of inflammation signal, we validated this observation in naïve C57BL/6 mice. Despite the lack of cardiac dysfunction in ponatinib treated naïve C57BL/6 mice, comprehensive immune profiling depicted upregulation of myocardial inflammation as evident by infiltrated immune cells (CD45 + TNFα + , CD45 + CD11b + F4/80 + Ly6C + CCR2 + , CD45 + Gal1 + ). Interestingly, we also demonstrated the downregulation of immune checkpoints over T cells (TCRαβ + CTLA4 + , TCRαβ + PD1 + ) in ponatinib treated hearts. Next, in the PO mouse model, ponatinib treated mice showed significant cardiac dysfunction with myocardial inflammation as reflected by increased frequencies of inflammatory parameters (TNFα + , IL1β + , IL6 + , MCP1 + , CXCL9 + ). Mechanistically, we demonstrated that ponatinib potentially suppresses PD-L1 expression over cardiomyocytes via inhibition of STAT3, subsequently leading to immune cells mediated myocardial inflammation. Conclusions: These findings uncover a novel mechanism of ponatinib induced cardiac inflammation leading to adverse cardiac function. It also suggests that strategies to attenuate inflammation may be an effective therapy to prevent ponatinib induced cardiac adverse events.
Risk of digestive cancers in a cohort of 69 460 five-year survivors of childhood cancer in Europe: the PanCareSurFup study
Authors: Raoul C Reulen, Kwok F Wong, Chloe J Bright, David L Winter, Daniela Alessi, Rodrigue M Allodji, Francesca Bagnasco, Edit Bárdi, Andrea Bautz, Julianne Byrne, Elizabeth AM Feijen, Miranda M Fidler-Benaoudia, Ibrahim Diallo, Stanislaw Garwicz, Desiree Grabow, Thorgerdur Gudmundsdottir, Joyeeta Guha, Nadia Haddy, Stine Høgsholt, Moncilo Jankovic, Peter Kaatsch, Melanie Kaiser, Rahel Kuonen, Helena Linge, Hilde Øfstaas, Cecile M Ronckers, Eva-Maria Hau, Roderick Skinner, Flora E van Leeuwen, Jop C Teepen, Cristina Veres, Wael Zrafi, Ghazi Debiche, Damien Llanas, Monica Terenziani, Giao Vu-Bezin, Finn Wesenberg, Thomas Wiebe, Carlotta Sacerdote, Zsuzsanna Jakab, Riccardo Haupt, Päivi M Lähteenmäki, Lorna Zadravec Zaletel, Claudia E Kuehni, Jeanette F Winther, Florent de Vathaire, Leontien C Kremer, Lars Hjorth, Michael M Hawkins
Journal: Gut (2020)

Background Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide. Methods The PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence. Results 427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN—comparable to the risk among members of the general population with at least two first-degree relatives affected. Conclusions Colonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken.
Trial in Progress: The Phase III, Randomized, Open-Label, Multicenter COMMODORE 2 Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Adult and Adolescent Patients with Paroxysmal Nocturnal Hemoglobinuria Not Previously Treated with Complement Inhibitors
Authors: Austin Kulasekararaj, Guangsheng He, Talha Munir, Jeffrey Pu, Antonio Risitano, Alexander Röth, Camelia S. Sima, Anita Appius, Alexandre Sostelly, Sasha Sreckovic, Charlotte Vignal, Jun-Ichi Nishimura
Journal: Blood (2020)
Abstract 458: Chronic Inhibition of Protein Kinase C Improves Coronary Endothelial Function in the Setting of Diabetes and Hypoxia
Authors: Zhiqi Zhang, Yuhong Liu, guangbin shi, Kim Justin, Song Yi, Frank W Sellke, Jun Feng
Journal: Circulation Research (2020)

Background: Both Diabetes (DM) and hypoxia/re-oxygenation (H/R) upregulate protein kinase C (PKC), resulting in coronary endothelial dysfunction. We hypothesized that chronic inhibition of PKC protects coronary endothelial function against DM and H/R injury. Methods: Genetically modified obesity and type-2 diabetic mice (female) were orally treated with or without selective PKCα/β inhibitor ruboxistaurin (10μg/g) for 4 weeks (n = 6/group). Coronary small arteries (70-110 μm in diameter) were then dissected from the harvested heart of mice. The isolated vessels were subjected to 60-min of hyperkalemic cardioplegic hypoxia (15°C) and then reperfused with oxygenated Krebs-Henseleit buffer for 60 minutes. At the end of 60-min re-oxygenation, all vessels was pretreated with endothelin-1 and then the responses to endothelium-dependent vasodilators, adenosine-diphosphate (ADP) and substance P were examined. Results: PKCα/β inhibition significantly improved the recovery of coronary endothelial function in the small coronary arteries of diabetic mice showing increased relaxation response to ADP and substance P in dose-dependent manner compared with the DM control (no-pretreatment alone) (*p&lt;0.05). Conclusion: Chronic inhibition of PKC significantly improved the recovery of coronary endothelial function against a period of cardiolpegic H/R in the diabetic microvasculature. These data suggest that the PKC inhibitor ruboxistaurin represents a novel potential therapeutic for coronary endothelial dysfunctionin patients with DM following cardioplegic ischemia and reperfusion.
Simulation Modeling of Cost-Savings from Conversion to Biosimilar Pegfilgrastim-Cbqv for the Prophylaxis of Chemotherapy-Induced Neutropenia, and Budget-Neutral Expanded Access to Prophylaxis and Anti-Neoplastic Therapy from Derived Cost-Savings in Non-Hodgkin Lymphoma
Authors: Ali McBride, Karen MacDonald, Ivo Abraham
Journal: Blood (2020)
Ehl Factors at Lower Than Standard Dose Achieve Satisfactory Surgical Haemostatsis in Haemophilia
Authors: Aby Abraham, Fouzia N., Anu Korula, Uday Prakash Kulkarni, Anup Devasia, Kavitha M Lakshmi, Sandeep Albert, Pradeep Poonoose, Sukesh Chandran Nair, Vikram Mathews, Biju George, Alok Srivastava
Journal: Blood (2020)
Lenograstim and Filgrastim Have a Similar Efficacy and Safety Profile in the Treatment of Chronic Neutropenia. a Study for the French SCN Registry:
Authors: Jean Donadieu, Blandine Beaupain, Fares bou Mitri, Flore Sicre de Fontbrune, Despina Moushous, Thierry Lamy, Aline Moignet Autrel, Elodie Gouache, Marlène Pasquet, Christine Bellanne-Chantelot
Journal: Blood (2020)