tbuckley/cabot-search huggingface dataset:
OP0207 The outcomes of limited cutaneous systemic sclerosis patients: a eustar database study
Authors: C. Frantz, D. Huscher, E. Hachulla, A. Balbir-Gurman, G. Riemekasten, E. Siegert, P. Airo, B. Joven, S. Vettori, F. Cozzi, S. Ullman, L. Czirjak, Y. Allanore
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Several studies have consistently showed that the extent of skin involvement has a major impact on disease prognosis in the diffuse cutaneous subtype of systemic sclerosis. The large majority of the ongoing clinical trials aim at identifying efficient drug in this subset. By contrast, little is known about the limited cutaneous subset (LcSSc) and the translation of the data coming for DcSSc to LcSSc is uncertain. <h3>Objectives</h3> Therefore, our aim was to investigate skin and lung involvement trajectories of LcSSc patients using the large EUSTAR registry. <h3>Methods</h3> We analysed the longitudinal data extracted from the EUSTAR cohort collected before February 2017. Worsening of skin fibrosis was defined by an increase in modified Rodnan skin score (mRSS) &gt;3.5 points from baseline to 2nd visit. Interstitial lung disease (ILD) was defined by any fibrosis on imaging (X-ray/computed tomography). Worsening of ILD was defined by a decrease of FVC &gt;10% from baseline to 2nd visit. For predicting models, predictors with p&lt;0.2 in the univariate analysis were included in the logistic regression analysis. <h3>Results</h3> 8013 LcSSc were included with a mean follow-up of about 3.3±3.7 years. At baseline, mean ±SD mRSS was 6±5 and ILD was present in 28.4% of all patients. Worsening of skin fibrosis was observed in 6.4% (19/298), 7.8% (97/1248) and 9.8% (289/2957) of LcSSc patients at 6, 12 and 24 months follow-up respectively. In multivariate analysis, variables predicting skin fibrosis progression were elevated European Scleroderma Study Group activity index (EScSG-AI) (OR [95 IC]: 1.22 [1.05–1.4], p=0.007) for 12 months progression and EScSG-AI (1.24 [1.13–1.38], p&lt;0.001) and mRSS (0.95 [0.93–0.98], p=0.001) for 24 months progression. Worsening of ILD was observed in 11.7% (23/196) and 19.9% (65/326) of LcSSc patients with ILD at baseline, at 12 and 24 months follow-up respectively. In multivariate analysis, variables predicting ILD progression at 24 months were EScSG-AI &gt;3 (OR [95 IC]: 3.8 [1.51–9.56], p=0.005), FVC (1.03 [1.01–1.04], p&lt;0.001) and LVEF (0.91 [0.85–0.97], p=0.005). <h3>Conclusions</h3> It appears that only few LcSSc patients progress for skin fibrosis ; this limits the use of mRSS in this subset and the potential of anti-fibrotic drugs of skin disease. However, a substantial rate of ILD progression was identified as well as relevant predictors. These results support the inclusion of LcSSc patients in SSc-ILD trials evaluating anti-fibrotic drugs. Our predictive models will be helpful to define enriched population in future clinical trials. <h3>Acknowledgements:</h3> <i>This work was supported by an unrestricted grant from INVENTIVA</i> <h3>Disclosure of Interest</h3> None declared
TICA: Transcriptional Interaction and Coregulation Analyzer
Authors: Stefano Perna, Pietro Pinoli, Stefano Ceri, Limsoon Wong
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract Transcriptional regulation is critical to cellular processes of all organisms. Regulatory mechanisms often involve more than one transcription factor (TF) from different families, binding together and attaching to the DNA as a single complex. However, only a fraction of the regulatory partners of each TF is currently known. In this paper, we present the Transcriptional Interaction and Coregulation Analyzer (TICA), a novel methodology for predicting heterotypic physical interaction of TFs. TICA employs a data-driven approach to infer interaction phenomena from chromatin immunoprecipitation and sequencing (ChIP-seq) data. Its prediction rules are based on the distribution of minimal distance couples of paired binding sites belonging to different TFs which are located closest to each other in promoter regions. Notably, TICA uses only binding site information from input ChIP-seq experiments, bypassing the need to do motif calling on sequencing data. We present our method and test it on ENCODE ChIP-seq datasets, using three cell lines as reference including HepG2, GM12878, and K562. TICA positive predictions on ENCODE ChIP-seq data are strongly enriched when compared to protein complex (CORUM) and functional interaction (BioGRID) databases. We also compare TICA against both motif/ChIP-seq based methods for physical TF–TF interaction prediction and published literature. Based on our results, TICA offers significant specificity (average 0.902) while maintaining a good recall (average 0.284) with respect to CORUM, providing a novel technique for fast analysis of regulatory effect in cell lines. Furthermore, predictions by TICA are complementary to other methods for TF–TF interaction prediction (in particular, TACO and CENTDIST). Thus, combined application of these prediction tools results in much improved sensitivity in detecting TF–TF interactions compared to TICA alone (sensitivity of 0.526 when combining TICA with TACO and 0.585 when combining with CENTDIST) with little compromise in specificity (specificity 0.760 when combining with TACO and 0.643 with CENTDIST). TICA is publicly available at http://geco.deib.polimi.it/tica/.
Comment on Li et al. Visual Inspection of Chromatograms Assists Interpretation of HbA1c: A Case Report. Diabetes Care 2018;41:1829–1830
Authors: Jie Li, Jie Lei, An-ping Xu, Yong Xia, Ling Ji
Journal: Diabetes Care (2018)

We read with interest the article by Li et al. (1). The authors reported a case with an extremely abnormal HbA1c value due to interference of a hemoglobin (Hb) variant. We agree with the authors regarding the necessity of visual inspection of chromatograms of HbA1c prior to reporting the results, especially in the scenario of discordance between HbA1c and other clinical findings. However, we believe some comments and suggestions for future investigation are important for exploring this issue.

Li et al. (1) should double-check their gene sequencing data, which were not included in the case report. We note that they identified a heterozygous mutation (c.242T>A, Leu81His) in …
Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries: analysis from the RIETE registry
Authors: Daniela Mastroiacovo, Francesco Dentali, Pierpaolo di Micco, Ana Maestre, David Jiménez, Silvia Soler, Joan Carles Sahuquillo, Peter Verhamme, Ángeles Fidalgo, Juan Bosco López-Sáez, Andris Skride, Manuel Monreal
Journal: European Respiratory Journal (2018)

<b>Real-life data from the RIETE study suggest only a few patients with pulmonary embolism at low risk of complications were treated at home or hospitalised for ≤5 days. Management of PE appeared quite variable in different countries.</b>http://ow.ly/o2b230mD8EY
Response to: ‘Ultrasound findings in palindromic rheumatism’ by Sanmarti <i>et al</i>
Authors: Kulveer Mankia, Maria-Antonietta D’Agostino, Paul Emery
Journal: Annals of the Rheumatic Diseases (2018)

We thank Sanmarti et al 1 for their interest in our recent paper in which we describe the distinct imaging phenotype of palindromic rheumatism (PR).2 As the authors point out, we identified a high prevalence of ultrasound (US) extra-capsular inflammation in flares of PR, often without coexistent US synovitis. This US pattern was specific for PR and may be useful in distinguishing PR from early persistent arthritis.

In an earlier US study of a Spanish PR cohort, Sanmarti and colleagues performed US assessment in 10 patients during flares of PR3 and reported US power Doppler synovitis in 7, with 5 of these fulfilling criteria for US-defined synovitis. The authors did not identify US periarticular changes, and none of these patients had periarticular inflammation clinically. This imaging …
Poly(lactic acid) nanoparticles and cell-penetrating peptide potentiate mRNA-based vaccine expression in dendritic cells triggering their activation
Authors: Anne-Line Coolen, Céline Lacroix, Perrine Mercier-Gouy, Emilie Delaune, Claire Monge, Jean-Yves Exposito, Bernard Verrier
Journal: Biomaterials (2018)
Management of Mucositis with the Use of Leucovorin As Adjunct to Pralatrexate in Treatment of Peripheral T-Cell Lymphomas (PTCL) — Results from a Prospective Multicenter Phase 2 Clinical Trial
Authors: Andrei R Shustov, Michi M Shinohara, Shaker R. Dakhil, Gajanan Bhat, Jasmine M. Zain
Journal: Blood (2018)
Mouse Necl-3 promoter methylation in TRAMP cells
Authors: Guimin Chang, Shuping Xu, Jeffrey R. Gingrich
Journal: Cancer Research (2006)

1592  Necl-3 is a member of the Nectin-like (Necls) molecule family which belongs to the larger immunoglobulin superfamily. Mouse Nectin-like 3 (mNecl-3) was cloned by RT-PCR based on the human sequence. The homology of mNecl-3 mRNA with hNecl-3 is about 89.8%, with an amino acid homology of 97.5%. This indicates that Necl-3 is highly conserved between mice and humans. Domain analysis demonstrated a predicted extracellular domain (EC) containing one Ig-like V -type domain, two Ig-like C2-type domains, a single hydrophobic trans-membrane domain, and a short intracellular domain (IC) containing two putative signaling motifs - protein 4.1 and PDZ-binding domains. One alternative splicing variant of mNecl-3 was also cloned and characterized. This variant of mNecl-3b lacked exon-9 encoding a proximal O-glycosylation site. The mNecl-3 gene is located in Contig CAAA01039711.1 including chromosome 16C1.3 locus, the syntenic region of human chromosome 3p12.1 which is among the most frequently lost in many types of cancer. Cell aggregation assays demonstrated mNecl-3 overexpression increased through homophilic interactions in a Ca2+/Mg2+-independent manner. Western analysis of a variety of mouse tissues indicated good specificity of rabbit polyclonal peptide antibodies in mice and that mNecl-3 was expressed in multiple normal tissues tested, especially brain, liver, kidney, lung, and prostate. The protein size of 60kD was similar to that in human prostate and suggestive of probable dimerization. However, mRNA and protein expression in some TRAMP cell lines was reduced when compared with expression in normal prostate epithelial tissue. To determine the mechanism of down-regulation of mNecl-3 in mouse prostate cancer, methylation of the mNecl-3 promoters was investigated. Promoter sequence analysis identified one large CpG island in the promoter region of mNecl-3. Bisulfite genomic sequencing analysis revealed distinct methylation patterns. The promoter was unmethylated in normal prostate epithelial tissue, but extensively methylated in TRAMP C2 sublines such as TRAMP-C2H and C2N (78.8% and 67.7% respectively) both of which are metastatic and partially methylated in TRAMP-C2D and C2G (29.8% and 13.8% respectively). A significant correlation between promoter hypermethylation and loss of mNecl-3 mRNA expression in TRAMP cell lines was demonstrated. Therefore we propose to assess the status of TRAMP tissues in different stages of PIN, cancer, and metastasis to elucidate the relationship of methylation and pathological status.
Abstract 16450: Impact of Cigarette Smoke, Next Generation Tobacco and Nicotine Products on the Cytotoxic, Oxidative and Pro-Inflammatory Status of THP-1 Cells
Authors: Coy Brunssen, Sindy Giebe, Anja Hofmann, Melanie Brux, Katherine Hewitt, Frazer Lowe, Henning Morawietz
Journal: Circulation (2017)

Introduction: Monocytes exhibiting a pro-inflammatory phenotype play a key role in adhesion and development of atherosclerotic plaques. Next generation tobacco and nicotine products (NGPs) are now widely used globally as an alternative to smoking. Little is known about their pro-inflammatory effects on monocytes. Hypothesis: We hypothesized that next generation tobacco and nicotine products might have a different impact on viability and gene expression in monocytes than conventional cigarettes. Methods: We investigated cell viability, anti-oxidant and pro-inflammatory gene and protein expression in THP-1 monocytes exposed to aqueous extracts of conventional cigarettes (CSE), a tobacco heating product (THP) and an electronic cigarette (EC). Pure nicotine was used as additional control. Results: Treatment with CSE reduced cell viability in a dose-dependent manner, whereas all other test agents showed no difference to control. At the highest non-lethal dose of CSE (20%) the following notable mRNA expression ...
Minimal Residual Disease (MRD) at Time of Complete Remission Is Commonly Detected in Acute Myeloid Leukemia (AML) Patients Age ≥60 Years and Significantly Impacts Outcome Based on Post-Remission Treatment Strategies: Prospective Analysis of ECOG-ACRIN (E-A) E2906 Phase III Trial
Authors: James M. Foran, Zhuoxin Sun, Elisabeth Paietta, Janis Racevskis, David F. Claxton, Hillard M Lazarus, Daniel A. Arber, Jacob M. Rowe, Jessica K. Altman, Aref Al-Kali, Hong Zheng, Keith W. Pratz, Edward R. Broun, Bayard L. Powell, Kristen Marie O'Dwyer, John Godwin, Yanming Zhang, Martin S. Tallman, Selina Luger, Mark R. Litzow
Journal: Blood (2018)
Results from a Phase II Study of Isatuximab As a Single Agent and in Combination with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma
Authors: Meletios A Dimopoulos, Sara Bringhen, Pekka Anttila, Marcelo Capra, Michele Cavo, Craig E. Cole, Cristina J Gasparetto, Vania T. M. Hungria, Matthew Jenner, Vladimir Vorobyev, Eduardo Yanez Ruiz, Jianyun Yin, Anthony Hamlett, Ravi Vij
Journal: Blood (2018)
Abstract 12556: Coronary Microvascular Dysfunction in Patients With Acromegaly: A Hint for their Increased Cardiovascular Risk
Authors: Sara Tellatin, Giulia Famoso, Francesca Dassie, Chiara Martini, Elena Osto, Pietro Maffei, Sabino Iliceto, Francesco Tona
Journal: Circulation (2013)

Background: Acromegaly (AC) increases the risk of cardiovascular diseases. We evaluated coronary flow reserve (CFR) by transthoracic Doppler echocardiography (TDE), as an index of coronary microvas...
Abstract 12960: Differential Pulse Arrival Time: A Novel Approach to Continuous Cuff-less Blood Pressure Monitoring
Authors: Jay A Pandit, Kyle Miller, Jung-en Wu, Sean D Connell, Sanjiv Shah
Journal: Circulation (2016)

Introduction: Blood pressure (BP) is a continuous and dynamic physiologic variable. The sphygmomanometer has forced clinicians to rely on singular snapshots of BP to make clinical decisions about BP control. Ambulatory cuff-based BP monitoring has demonstrated superiority over the conventional, single-point office-based cuff measurement and has unveiled the important concept of nocturnal BP dipping; however, it is plagued by poor compliance leading to limited use. Thus, there is an unmet need for an unobtrusive continuous ambulatory BP monitor. Current methods for continuous, non-invasive ambulatory BP monitoring include the use of vascular unloading and pulse transit time. However, both of these techniques have limitations. We therefore propose a novel method—differential pulse arrival time (DPAT)—to continuously estimate BP non-invasively. We hypothesized that continuous DPAT-derived BP correlates well with cuff-based measurement of BP at rest and during a cold-pressor maneuver. Methods: Normotensive subjects were fitted with a DPAT device and a Finapres Nova ambulatory BP monitor. Each subject underwent a standardized protocol consisting of 2 minutes at rest, 2 minutes cold pressor at 40 o F, and 2 minutes at rest. The raw data from the DPAT device was then time-matched and compared with the Finapres BP trend. Results: Over 100 million DPAT data points were collected from 12 normotensive subjects (age range 20-50). DPAT correlated with Finapres blood pressures with a correlation coefficient of 0.8 and there was no evidence of bias on Bland-Altman plot. (Figure 1). The root mean square error for the predicted blood pressure was ±4.76 mmHg for systolic BP and ±4.03 mmHg for diastolic BP. Conclusions: Differential pulse arrival time obtained by an optical-sensor based system is a viable approach to monitoring continuous BP in normotensives. Future studies in elderly, hypertensive individuals are warranted.
Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation
Authors: Amelia J. Hessheimer, Elisabeth Coll, Ferrán Torres, Patricia Ruíz, Mikel Gastaca, José Ignacio Rivas, Manuel Gómez, Belinda Sánchez, Julio Santoyo, Pablo Ramírez, Pascual Parrilla, Luis Miguel Marín, Miguel Ángel Gómez-Bravo, Juan Carlos García-Valdecasas, Javier López-Monclús, Andrea Boscá, Rafael López-Andújar, Jiliam Fundora-Suárez, Jesús Villar, Álvaro García-Sesma, Carlos Jiménez, Gonzalo Rodríguez-Laíz, Laura Lladó, Juan Carlos Rodríguez, Manuel Barrera, Ramón Charco, Jose Ángel López-Baena, Javier Briceño, Fernando Pardo, Gerardo Blanco, David Pacheco, Beatriz Domínguez-Gil, Víctor Sánchez Turrión, Constantino Fondevila
Journal: Journal of Hepatology (2018)
Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway
Authors: Shanshan Qi, Lingyuan Guo, Shuzhen Yan, Robert J. Lee, Shuqin Yu, Shuanglin Chen
Journal: Acta Pharmaceutica Sinica B (2018)

Over recent decades, many studies have reported that hypocrellin A (HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy (PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation (iTRAQ) 2D liquid chromatography with tandem mass spectrometric (LC–MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspase inhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation, and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species (ROS) generations. Further studies showed that PDT treatment with 0.08 µmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome c, and activation of caspase-3, -9, and -7. Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.
The Impact of Early Post-Transplant Cyclosporine Induced Acute Nephrotoxicity on Long Term Renal Function in 2-Year Survivors of Allogeneic Hematopoietic Stem Cell Transplantation: A Cohort Retrospective Study
Authors: Reem Alharbi, Mahmoud Aljurf, Raid El Fakih, Mohammad Al Nahedh, Majed Huessein, Zubeir Ahmed Nurgat, Almohareb Fahad, Naeem A. Chaudhri, Fahad Z. Alsharif, Hazza A. Alzahrani, Walid Rasheed, Amr Suleiman Hanbali, Marwan Shaheen, Feras Al Fraih, Saud Alhayli, Riad Youniss, Shahrukh Hashmi, Syed Osman Ahmed
Journal: Blood (2018)
Abstract 13409: Left Ventricular Remodeling and Function Following Aortic Valve Replacement for Low-Flow, Low-Gradient Aortic Stenosis With Preserved Ejection Fraction-Results From the TOPAS Study
Authors: Abdellaziz Dahou, Marie-Annick Clavel, Jean G Dumesnil, Romain Capoulade, Henrique B Ribeiro, Mario Senechal, Kim O’Connor, Josep Rodés-Cabau, Philippe Pibarot
Journal: Circulation (2015)

Background: Aortic valve replacement (AVR) is recommended (IIa) in symptomatic patients with paradoxical low-flow, low-gradient aortic stenosis (PLF-LG AS). This entity is characterized by pronounced LV concentric remodeling with impaired LV filling and reduced LV longitudinal systolic function and stroke volume despite preserved LV ejection fraction (p-EF). However, there is lack of data about the evolution of LV geometry and function following AVR in these patients. Methods: We prospectively enrolled thirty-two patients (age=71±12 years; 59% men) with PLF-LG AS (SVi&lt;35 mL/m2, mean gradient&lt;40 mmHg, indexed aortic valve area [AVA] 50%) who underwent AVR within 3 months following inclusion. Stroke volume was measured in the LV outflow tract by pulsed-wave Doppler and indexed for body surface area (SVi). Global left ventricular longitudinal strain (GLS) was measured by 2D speckle tracking. Results: Following AVR, mean gradient decreased (15±8 mmHg post vs. 30±7 pre AVR) and AVA increased significantly (1.40±0.31 vs. 0.70±0.12 cm2) (all p&lt;0.0001). AVR was associated with a positive LV remodeling with an increase in LV end-diastolic diameter (46±4 vs. 44±4 vs mm; p=0.0027) and volume (99±21 vs. 89±20 ml, p=0.003) and a decrease in relative wall thickness (0.46±0.06 vs. 0.58±0.11; p=0.0004) and LV mass (175±37 vs. 207±44 g; p=0.002). SVi increased significantly from baseline to 1 year (36±7 vs. 31±3 ml/m2; p=0.0002), whereas LVEF remained unchanged (63±6 vs 63±7; p=NS). SVi increased significantly in the subset of patients with mild to moderate DD at baseline (all p&lt;0.05) but not in those with severe DD (p=NS). GLS also increased significantly from baseline to 1 year (17±4 vs. 14.5±4%; p=0.03). There was a significant correlation between post-AVR increase in GLS and increase in SVi (r=0.52; p=0.02). Conclusion: The findings of this study demonstrate that in patients with PLF-LG AS and p-EF, AVR is associated with an increase in LV stroke volume which is mainly due to positive LV remodeling and improvement in LV longitudinal systolic function. Our results provide further support to the ACC/AHA recommendations with regard to indication of AVR in these patients.
The Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) Made Simple for Medical and Radiation Oncologists
Authors: Ryan T. Jones, Bonnie Helm, Dominick Parris, Stephen S. Grubbs, Hak Choy, Ksenija Kapetanovic
Journal: JAMA Oncology (2018)

<h3>Importance</h3> The Medicare Access and CHIP (Children's Health Insurance Program) Reauthorization Act of 2015 (MACRA) instituted significant changes in payment methods for many Medicare Part B billing providers (eg, clinicians and health care facilities). Fulfilling its measures satisfactorily and adhering to its reporting requirements will significantly affect reimbursement, yet previous surveys suggest that clinicians' understanding of MACRA is poor. This review provides fundamental background on MACRA for medical and radiation oncologists. <h3>Observations</h3> The Congress.gov database, PubMed, and the Center for Medicare &amp; Medicaid Services website were searched for legislature and publications relevant to the history, structure, and predicted future for MACRA. MACRA originated from concerns of poor-quality care and from the failure of the traditional fee-for-service model and the Medicare Sustainable Growth Rate method to control rising health care costs. The Quality Payment Program of MACRA started the Merit-based Incentive Payment System (MIPS) and the Alternative Payment Model (APM) system to move from the traditional fee-for-service model to value-based payment. The most recent legislation extended the transitional period for MIPS and removed drugs and biologics covered by Medicare Part B. Currently, the primary APM for medical oncology is the Oncology Care Model, and an APM for radiation oncology is awaiting approval. Despite recent calls from the Medicare Payment Advisory Commission to end MIPS, there is no indication that either MIPS or APMs will be repealed in the near future. <h3>Conclusions and Relevance</h3> MACRA affects the methods of payment for many Medicare Part B billing providers; the included summary equips medical and radiation oncologists with an understanding of its structure and requirements.