tbuckley/cabot-search huggingface dataset:
S824 A PHASE 3 RANDOMIZED, OPEN‐LABEL, MULTICENTER STUDY OF ISATUXIMAB, POMALIDOMIDE, AND LOW‐DOSE DEXAMETHASONE VS POMALIDOMIDE AND LOW‐DOSE DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM)
Authors: M. Attal, P.G. Richardson, S.V. Rajkumar, J. San‐Miguel, M. Beksac, I. Spicka, X. Leleu, F. Schjesvold, P. Moreau, M.A. Dimopoulos, J.S.‐Y. Huang, J. Minarik, M. Cavo, H.M. Prince, S. Mace, K.P. Corzo, F. Campana, S. Le‐Guennec, F. Dubin, K.C. Anderson
Journal: HemaSphere (2019)

Background: Despite recent advances, multiple myeloma (MM) remains incurable, and new treatment options are needed to continue to improve patient outcomes. This is the first randomized, phase 3 trial of an anti‐CD38 antibody in combination with pomalidomide (P) and dexamethasone (d) in RRMM. Aims: The primary objective of this phase 3 trial (NCT02990338) was to demonstrate progression free survival (PFS) improvement of isatuximab (Isa), a novel anti‐CD38 monoclonal antibody targeting a specific epitope, combined with Pd versus (vs) Pd in RRMM. Methods: Patients (pts) with RRMM who received ≥2 prior lines, including lenalidomide (len) and a proteasome inhibitor (PI), refractory to last therapy were enrolled. IsaPd arm received Isa 10 mg/kg IV weekly for first 4 weeks (wks), then every 2 wks. Both arms received approved schedules of pom and dex (4 mg PO days 1–21; 40 mg [20 mg if &gt;75 yrs] PO or IV weekly) every 28 days until progression or unacceptable toxicity. Results: 307 pts (154 IsaPd, 153 Pd) were randomized and analyzed (ITT). Patient characteristics were well balanced across arms. Median age: 67 (36–86) yrs; median prior lines of therapy: 3 (2–11); estimated GFR: &lt;60 ml/min in 33.9% pts; 92.5% refractory to len, 75.9% to PI; and 19.5% pts had high‐risk cytogenetics. At median follow‐up of 11.6 months (mos), median PFS was 11.5 mos IsaPd vs 6.5 mos Pd; HR 0.596 (95% CI 0.44–0.81), P = 0.001. PFS benefit was consistent across all major subgroups. ORR (≥PR) was 60.4% IsaPd vs 35.3% Pd, P &lt; 0.0001. VGPR rate or better was 31.8% IsaPd vs 8.5% Pd, and MRD negativity (NGS, 10 −5 ) was seen in 5.2% IsaPd pts vs 0% Pd. At analysis date, overall survival (OS) was immature (99 events) but a trend to OS improvement in IsaPd (vs Pd) was observed (HR 0.687; 95% CI 0.461–1.023). Median treatment duration was 41 wks IsaPd vs 24 wks Pd; median Isa infusion (inf.) duration was 3.3 h at 1 st inf. and 2.8 h at subsequent inf. Grade ≥3 AEs were observed in 86.8% IsaPd vs 70.5% Pd; 7.2% IsaPd and 12.8% Pd pts discontinued due to AEs; 7.9% IsaPd and 9.4% Pd pts died due to AEs. Inf. reactions were reported in 38.2% (2.6% grade 3–4) IsaPd. Grade ≥3 infections were seen in 42.8% IsaPd and 30.2% Pd, grade ≥3 neutropenia in 84.9% (febrile 11.8%) IsaPd and 70.1% (febrile 2.0%) Pd. Summary/Conclusion: Isatuximab in combination with pomalidomide and dexamethasone significantly improved PFS and ORR vs pomalidomide and dexamethasone, with a manageable safety profile. Isatuximab in combination with pomalidomide and dexamethasone is an important new treatment option for the management of RRMM.
Subjugation of TGFβ Signaling by Human Papilloma Virus in Head and Neck Squamous Cell Carcinoma Shifts DNA Repair from Homologous Recombination to Alternative End Joining
Authors: Qi Liu, Lin Ma, Trevor Jones, Luis Palomero, Miquel Angel Pujana, Haydeliz Martinez-Ruiz, Patrick K. Ha, John Murnane, Isabel Cuartas, Joan Seoane, Michael Baumann, Annett Linge, Mary Helen Barcellos-Hoff
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Following cytotoxic therapy, 70% of patients with human papillomavirus (HPV)-positive oropharyngeal head and neck squamous cell carcinoma (HNSCC) are alive at 5 years compared with 30% of those with similar HPV-negative cancer. Loss of TGFβ signaling is a poorly studied consequence of HPV that could contribute to patient outcome by compromising DNA repair. Experimental Design: Human HNSCC cell lines (n = 9), patient-derived xenografts (n = 9), tissue microarray (n = 194), TCGA expression data (n = 279), and primary tumor specimens (n = 10) were used to define the relationship between TGFβ competency, response to DNA damage, and type of DNA repair. Results: Analysis of HNSCC specimens in situ and in vitro showed that HPV associated with loss of TGFβ signaling that increased response to radiation or cisplatin. TGFβ suppressed miR-182, which inhibited both BRCA1, necessary for homologous recombination repair (HRR), and FOXO3, required for ATM kinase activity. TGFβ signaling blockade by either HPV or inhibitors released miR182 control, compromised HRR and increased response to PARP inhibition. Antagonizing miR-182 rescued the HRR deficit in HPV-positive cells. Loss of TGFβ signaling unexpectedly increased repair by error prone, alternative end-joining (alt-EJ). Conclusions: HPV-positive HNSCC cells are unresponsive to TGFβ. Abrogated TGFβ signaling compromises repair by HRR and increases reliance on alt-EJ, which provides a mechanistic basis for sensitivity to PARP inhibitors. The effect of HPV in HNSCC provides critical validation of TGFβ’s role in DNA repair proficiency and further raises the translational potential of TGFβ inhibitors in cancer therapy.
Clinicopathologic comparison of Rowell syndrome, erythema multiforme, and subacute cutaneous lupus erythematosus
Authors: Mitch Herold, Colton B. Nielson, Diana Braswell, Kimberly Merkel, Addie Walker, Jena Auerbach, Jyoti Kapil, Kiran Motaparthi
Journal: Journal of the American Academy of Dermatology (2019)
Abstract 1101: Cardio-protective Action of Follistatin Like-1, a Secreted Anti-apoptotic Factor Regulated by Akt1
Authors: Yuichi Oshima, Noriyuki Ouchi, Kaori Sato, David R Pimentel, Yasuhiro Izumiya, Stephan Schiekofer, Kenneth Walsh
Journal: Circulation (2007)

Recent reports have proposed the importance of secreted factors that display cardioprotective effects through autocrine / paracrine mechanisms. Identification of these factors will provide novel th...
Abstract 18514: Epigenetic Regulation of Chromatin Remodeler CHD5 in Stem Cells During Cardiac Differentiation and Stem Cell Mediated Myocardial Repair and Function After Myocardial Infarction
Authors: Yan Tang, Yujia Yue, Venkata Naga Srikanth Garikipati, Suresh K Verma, David Goukassian, Zhongjian Cheng, Chunlin Wang, May Cao, Raj Kishore
Journal: Circulation (2017)

Poor differentiation ability might be the barrier for the stem cell based therapy in ischemic myocardium. Epigenetic regulation play a critical role in this cell fate commitment, however, the mecha...
PB1653 HIGH RASD1 TRANSCRIPT LEVELS AT DIAGNOSIS PREDICTED POOR SURVIVAL IN ADULT B‐CELL ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS
Authors: S. Wang, C. Wang, Y. Liu
Journal: HemaSphere (2019)

Background: B‐cell acute lymphoblastic leukemia (B‐ALL) in adults remains a highly challenging disease. Identifying new prognostic biomarkers is necessary to help select the best therapeutic schedules and to improve prognosis. We performed bioinformatics analyses of transcriptomic data to identify aberrantly‐expressed mRNA transcripts in B‐ALL and focused on RASD1 (Ras‐related dexamethasone‐induced 1) which is a member of the RAS family and plays important roles in tumor growth and expansion. To date, no reports on RASD1 and B‐ALL have been reported. Aims: To examine the expression and clinical significance of RASD1 in adults with B‐ALL; to explore effects of RASD1 on biological function of B‐ALL. Methods: Fifty‐three consecutive adults with de novo B‐ALL were enrolled in this study. The RASD1 transcript levels were determined by TaqMan‐based real time quantitative PCR (RQ‐PCR) at the time of diagnosis. RASD1‐over‐expression cell models were constructed to study the biological function of RASD1 in B‐ALL. The cell proliferation was detected by CCK‐8; cell apoptosis and cell cycle were analyzed by flow cytometry. Results: Our data suggested that RASD1 was abnormally overexpressed in B‐ALL. High RASD1 transcript levels at diagnosis were associated with lower survival probabilities (44% [20% &gt; 61%] vs. 79% [60% &gt; 97%]; P = 0.037) and were also an independent prognostic factor in adult B‐ALL (HR = 4.9 [1.5‐15.9]; P = 0.008). Functional in vitro analyses indicated that RASD1 promoted cell proliferation, cell cycle progression and chemotherapy resistance and inhibited cell apoptosis. Bioinformatic analyses also showed that high RASD1 expression in cells correlated with positive regulation of cell proliferation as well as nucleosome assembly and telomere organization. Summary/Conclusion: These data demonstrated that RASD1 might serve as a novel prognostic biomarker for adult B‐ALL and as a potential therapeutic target in adult B‐ALL patients.
Abstract 14770: Aortic Valve Calcium Symmetry and Distribution to Predict Localization of Paravalvular Leakage after Transcatheter Aortic Valve Implantation
Authors: Daniel Wendt, Björn Plicht, Philipp Kahlert, Konradin Hartmann, Thomas Konorza, Raimund Erbel, Heinz Jakob, Matthias Thielmann
Journal: Circulation (2012)

Objectives: Calcium distribution, topography and morphology in aortic valve stenosis may have an impact on the localisation of postprocedural paravalvular leakages (PVL) following transcatheter aor...
Abstract 17794: Correlation of ECG Voltages to Echocardiographic LV Mass in a Large Athletic Adolescent Screening Program
Authors: Richard Czosek, James Cnota, Karine Guerrier, Timothy Knilans, Michelle Faust, Jesse Pratt, Anderson B Jeffrey
Journal: Circulation (2013)

Background: In an attempt to detect underlying disease processes that may place adolescent athletes at risk for sudden cardiac death, some have advocated for population based ECG screening. Controv...
Abstract 19089: Endothelial Extracellular Signal-Regulated Kinase 2 Increases Blood Pressure and Induced Endothelial Dysfunction and Insulin Resistance in Mice With High Fat High Sucrose Diet
Authors: Atsushi Sato, Yasushi Satoh, Shogo Endo, Toyokazu Kimura, Ayumu Osaki, Shunpei Horii, Kei Ito, Takayuki Namba, Takesshi Adachi
Journal: Circulation (2017)

Introduction: Metabolic syndrome (MetS) is well known as the risk of cardiovascular diseases associated with endothelial dysfunction, however, the mechanism is not fully clarified. Insulin resistan...
PF618 PROGNOSTIC IMPACT OF 18F‐FDG PET/CT IN PATIENTS WITH MULTIPLE MYELOMA PRESENTING WITH RENAL IMPAIRMENT
Authors: S.‐H. Jung, S.‐Y. Ahn, G.‐Y. Song, M.H. Heo, D.‐H. Yang, J.‐S. Ahn, H.‐J. Kim, J.‐J. Lee
Journal: HemaSphere (2019)

Background: 18 F‐fluorodeoxyglucose ( 18 F‐FDG) positron emission tomography/computed tomography (PET/CT) has become a standard imaging technique for predicting prognosis in multiple myeloma (MM), but have potential inaccuracies in patients with renal impairment (RI). Aims: In this study, we investigated the prognostic role of 18 F‐FDG PET/CT in patients with MM presenting with RI. Methods: Retrospective data for 74 patients with MM and RI between March 2012 and March 2017 were analyzed. Renal function was assessed using the estimated glomerular filtration rate (eGFR), which was calculated by the simplified Modification of Diet in Renal Disease (MDRD) formula. RI was defined as an eGFR of &lt;60 mL/min/1.73 m 2 at initial diagnosis. Severe RI was defined as eGFR &lt;30 mL/min/1.73 m 2 . 18 F‐FDG PET/CT was performed prior to induction therapy and PET/CT positivity was defined as the presence of more than three focal lesion (FL) or the presence of extramedullary disease (EMD). Results: A total of 29 patients (39.2%) had more than three FLs and 12 (16.2%) had EMD on baseline 18 F‐FDG PET/CT. Thirty patients (40.5%) demonstrated PET/CT positivity. The median eGFR was 37.9 mL/min (range 3.0–59.8) and 24 (32.4%) had severe RI at initial diagnosis. Over the median follow‐up duration of 37.5 months, 54 patients (73.0%) had progressed and 22 (29.7%) had died by the time of the last follow‐up visit. The median progression free survival (PFS) was 24.2 months (95% CI, 17.4–31.1) and the median overall survival (OS) was 68.3 months (95% CI, 44.1–92.5). Patients with PET/CT positivity had significantly inferior survival outcomes than those with PET/CT negativity (PFS, 12.7 months vs. 34.0 months, P &lt; 0.001; OS, 42.5 months vs. not reached, P = 0.012). In patients with severe RI, PET/CT positivity was significantly associated with poorer PFS and OS (PFS, 12.7 months vs 34.4 months, P = 0.011; OS, 42.4 vs not reached, P = 0.081). By multivariate analyses, PET/CT positivity was independently prognostic factor for PFS and OS in total patients. Summary/Conclusion: 18 F‐FDG PET/CT may be useful imaging technique for predicting survival outcomes in patients with MM presenting with RI. image
Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL
Authors: Qiong Zhang, Hui Hu, Si-Yi Chen, Chun-Jie Liu, Fei-Fei Hu, Jianming Yu, Yaohui Wu, An-Yuan Guo
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor efficacy in clinical trials. In this study, we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells, and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g., CD8+ T cells and natural killer (NK) cells, in the bone marrow. Additionally, CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways, including the NK cell mediated cytotoxicity and NOD-like receptor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g., miR-148a-3p and miR-375), acting as oncogenes or tumor suppressors, could regulate the crosstalk between the genes encoding transcription factors (TFs; e.g., JUN and FOS) and histones (e.g., HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore, many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g., FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for further understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.
AB0906 RELATIONSHIP BETWEEN FIBROMYALGIA AND TRUNK MUSCLE PERFORMANCE
Authors: Cevriye Mülkoğlu, Sühan Taşkın, Seçil Vural, Başak Mansız-Kaplan, Hakan Genç
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Muscle performance is adversely affected by pain, fatigue and low aerobic capacity in fibromyalgia syndrome(FMS). <h3>Objectives</h3> We compared trunk muscle performance of women with FMS and healthy individuals who have similar age and body mass index (BMI). <h3>Methods</h3> A total of 37 women with FMS and 32 healthy women were included this study. The demographic and clinical characteristics of the participants such as age, height, weight, body mass index (BMI), occupations, exercise habits were recorded. In semi-standing position with isokinetic dynamometer (BIODEX) at 60 ° -90 ° -120 °/second (s) angular velocities, trunk flexor and extensor muscle performances were evaluated. Flexor (flex) peak torque (PT), extensor (ext) PT values and flex/ext PT ratio (%) were noted. <h3>Results</h3> The mean age was 43.9 ± 8.1 years in FMS group and 43,7 ± 6,7 in control group. The mean BMI was 27.5 ± 4.19 in FMS group and 26.4 ± 4.08 in control group. There was no significant difference between the groups in terms of age and BMI (p&gt; 0.05). As a result of isokinetic measurements of trunk muscles, extensor PT values were found significantly lower in women with FMS than C group at all three angular velocities (p &lt;0.05). The flexor PT values also were lower in FMS group but no statistically significance in flexor PT values between the groups (p&gt;0.05). When flexor/extensor PT ratio was compared, it was seen that this ratio increased in the FMS group. <h3>Conclusion</h3> There are many studies in the literature assessing upper and lower extremity muscle performances in FMS (1-2). To our knowledge, we first evaluated trunk muscle performances of patients with FMS and we found that trunk muscles, especially extensors, were significantly weaker in FMS group. As a result, in treatment of FMS, there is a need for more comprehensive randomized controlled studies showing the importance of strengthening exercises to improve trunk muscle performance. <h3>References</h3> [1] Yetişgin A, Tiftik T, Kara M, Karabay İ, Akkuş S, Ersöz M. Isokinetic muscle performance of the hip and ankle muscles in women with fibromyalgia.Int J Rheum Dis2016; 19 (6): 551-6. [2] Güler H, Yıldızgören MT, üstün N, Paksoy H, Turhanoğlu AD. Isokinetic Assessment of the Wrist Muscles in Females With Fibromyalgia. Arch of Rheumatol 2016; 31(3): 215-20. <h3>Disclosure of Interests</h3> None declared
Abstract 13688: Randomized, Double-Blind, Placebo-Controlled Pilot Trial of Autologous CD34+ Cell Therapy for Severe Intermittent Claudication: Interim Results
Authors: Douglas W Losordo, Timothy D Henry, Melina R Kibbe, Marc Krichavsky, Farrell Mendelsohn
Journal: Circulation (2011)

Background: Surgical bypass techniques and percutaneous catheter-based interventions may be used to successfully revascularize the limbs of patients with claudication. In many patients, however, th...
Misrecognition and Critical Consciousness — An 18-Month-Old Boy with Pneumonia and Chronic Malnutrition
Authors: Héctor Carrasco, Luke Messac, Seth M. Holmes
Journal: New England Journal of Medicine (2019)

Interview with Dr. Héctor Carrasco on strategies for uncovering and addressing the fundamental causes of complex health problems. (10:14)Download An 18-month-old boy in La Soledad, Mexico, presents with pneumonia, to which he was predisposed by malnutrition. When nutrition education and food-production efforts fail, a physician and a community collaborative work to elucidate the deeper roots of the problem.
Abstract P130: Ideal Cardiovascular Health and Incident Cardiovascular Disease: Heterogeneity Across Event Phenotype and Contribution of Multiple Biomarkers. The Prime Study
Authors: Bamba Gaye, Muriel Tafflet, Dominique Arveiler, Michèle Montaye, Wagner Aline, Jean Bernard Ruidavets, Frank Kee, Alun Evans, Philippe Amouyel, Jean Ferrieres, Jean philippe Empana
Journal: Circulation (2017)

Background: To which extent the association between ideal cardiovascular health (CVH) and incident vascular events differ by main coronary heart disease (CHD) and main stroke phenotype is currently unknown. Furthermore, data on potential mediating factors underlying the association of ideal CVH with outcomes are lacking. Aims: We aimed to 1) quantify the association between ideal CVH and incident CHD and stroke, 2) to assess for potential heterogeneity across main CHD and main stroke phenotypes and between CHD and stroke; and 3) to assess the mediating effect of a selected panel of key circulatory biomarkers from different relevant disease pathways. Methods and Results: A total of 9312 men middle-aged men (50-59 years) free of CHD and stroke were recruited in the framework of WHO MONICA centres in Lille, Strasbourg, Toulouse (France) and Belfast (Northern Ireland) between 1991 and 1993 and enrolled in the PRIME study. According to the American Heart Association, men with 0-2, 3-4 and 5-7 metrics at the ideal level were categorized as having poor, intermediate and ideal CVH respectively. Hazards ratios (HRs) were estimated using Cox proportional hazards regression and were adjusted for age, centre, education, living alone, marital status, family history of CHD and blood fibrinogen. The contribution of baseline circulating, endothelial inflammatory and haemostatic biomarkers was explored in a case control study nested within the PRIME cohort and settled after 10 years of follow-up. An ideal CVH was observed in 7% of the participants. After a median follow-up of 10 years, 614 first CHD events (myocardial infarction, angina, coronary death) and 117 first stroke events (ischaemic and non ischaemic) were adjudicated. Compared to those with poor CVH, those with an ideal CVH at baseline had a 72% lower risk of CHD (HR=0.28; 95% CI: 0.17; 0.46) and a 76% lower risk of stroke (HR=0.24; 95% CI: 0.06; 0.98) in multivariate analysis. No heterogeneity was detected across main CHD and main stroke phenotypes. While significantly lower mean concentrations of hs-CRP, IL-6, ICAM-1, fibrinogen and von Willbrandt factor were noted in subjects with ideal or intermediate as compared to poor CVH status in the controls, none of these biomarkers contribute to the association of CVH with future CHD. Conclusion: In this study ideal CVH was associated with a substantially lower risk of CHD and stroke, without any difference across phenotypes. Neither inflammatory, endothelial nor haemostatic biomarkers explained the lower risk of CHD in men with ideal CVH.
Host-derived fecal microRNAs can indicate gut microbiota healthiness and ability to induce inflammation
Authors: Emilie Viennois, Benoit Chassaing, Anika Tahsin, Adani Pujada, Lixin Wang, Andrew T Gewirtz, Didier Merlin
Journal: Theranostics (2019)

Disruption of intestine-microbiota symbiosis can result in chronic gut inflammation. We hypothesize that assessing the initial inflammatory potential of the microbiota in patients is essential and that host-derived miRNAs, which can be found in feces, could fulfill this function. We investigated whether the gut microbiota composition impacts the fecal miRNA profile and thereby indicates its ability to influence intestinal inflammation. Methods: We used high-throughput qPCR to compare fecal miRNA profile between germ-free and conventional mice. Conventionalization of germfree mice by various colitogenic and non-colitogenic microbiotas (IL10-/- and TLR5-/- associated microbiota) was performed. Results: We identified 12 fecal miRNAs impacted by the presence of a microbiota. Conventionalization of germfree mice by various colitogenic and non-colitogenic microbiotas associated with the development of intestinal inflammation (IL10-/- and TLR5-/- associated microbiota) yielded distinctively altered fecal miRNA profiles compared to that of mice receiving a "healthy" microbiota. Correlation analysis revealed the existence of interactions between the 12 abovementioned miRNAs and specific microbiota members. Conclusion: These results showed that fecal miRNA profile can be differentially and specifically impacted by microbiota composition, and that miRNA could importantly serve as markers of the colitogenic potential of the microbiota. This is particularly relevant to assess individual state of the microbiota in patients with dysbiosis-related disorders, such as IBD and potentially determine their ability to respond to therapeutics.