tbuckley/cabot-search huggingface dataset:
Abstract 10968: Angiotensin Receptor Neprilysin Inhibition Improves Flow Mediated Dilatation of Brachial Artery in Heart Failure Patients With Reduced Ejection Fraction
Authors: Sercan Okutucu, Begum Yetis Sayin, Hakan Aksoy, Ali Oto
Journal: Circulation (2018)

Introduction: Angiotensin receptor neprilysin inhibitor (ARNI, sacubitril/valsartan) has demonstrated greater benefit as compared to enalapril in decreasing morbidity and mortality in heart failure...
3D‐Printed Hydrogel Composites for Predictive Temporal (4D) Cellular Organizations and Patterned Biogenic Mineralization
Authors: Joselle M. McCracken, Brittany M. Rauzan, Jacob C. E. Kjellman, Mikhail E. Kandel, Yu Hao Liu, Adina Badea, Lou Ann Miller, Simon A. Rogers, Gabriel Popescu, Ralph G. Nuzzo
Journal: Advanced Healthcare Materials (2018)

Abstract Materials chemistries for hydrogel scaffolds that are capable of programming temporal (4D) attributes of cellular decision‐making in supported 3D microcultures are described. The scaffolds are fabricated using direct‐ink writing (DIW)—a 3D‐printing technique using extrusion to pattern scaffolds at biologically relevant diameters (≤ 100 µm). Herein, DIW is exploited to variously incorporate a rheological nanoclay, Laponite XLG (LAP), into 2‐hydroxyethyl methacrylate (HEMA)‐based hydrogels—printing the LAP–HEMA (LH) composites as functional modifiers within otherwise unmodified 2D and 3D HEMA microstructures. The nanoclay‐modified domains, when tested as thin films, require no activating (e.g., protein) treatments to promote robust growth compliances that direct the spatial attachment of fibroblast (3T3) and preosteoblast (E1) cells, fostering for the latter a capacity to direct long‐term osteodifferentiation. Cell‐to‐gel interfacial morphologies and cellular motility are analyzed with spatial light interference microscopy (SLIM). Through combination of HEMA and LH gels, high‐resolution DIW of a nanocomposite ink (UniH) that translates organizationally dynamic attributes seen with 2D gels into dentition‐mimetic 3D scaffolds is demonstrated. These analyses confirm that the underlying materials chemistry and geometry of hydrogel nanocomposites are capable of directing cellular attachment and temporal development within 3D microcultures—a useful material system for the 4D patterning of hydrogel scaffolds.
P020 Characterization of Met Exon 14 Skipping and Association with Clinical Outcomes of Crizotinib in Chinese Lung Cancers
Authors: H. Yang, C. Zhou, Y. Su, Z. Zhou, P. Chen, M. Yang, C. Li, W. Guo, W. Zhao, K. Lu, J. Yin, J. Chen, Z. Li, X. Yu, X. Xu, J. Xiang, T. Zhang, B. Li, L. Zhang, H. Liu, N. Yang
Journal: Journal of Thoracic Oncology (2018)
A phase I/II trial of very low to low-dose continuous azacitidine in combination with standard doses of lenalidomide and low-dose dexamethasone in patients with relapsed or refractory multiple myeloma.
Authors: Frederic J. Reu, Dale Grabowski, Reda Z. Mahfouz, Hillard M. Lazarus, Robert M. Dean, Beth Faiman, Janice Reed, Mary Ann Karam, Kimberly Hamilton, Sherry Fada, Matt E. Kalaycio, Jason Neil Valent, Christy Joy Samaras, Ronald M. Sobecks, Linda McCowen, Jamie Elberson, Hien Liu, Yogen Saunthararajah, Yap Chew, Mitchell R. Smith
Journal: Journal of Clinical Oncology (2015)

8584 Background: Azacitidine (AZA) may overcome drug resistance of relapsed or refractory multiple myeloma (RRMM).Continuous administration should maximize epigenetic effects and safety. Methods: Lenalidomide (len) 25mg (10mg if GFR 30-59 ml/min) d1-21 every 28d and dexamethasone (dex) 40mg weekly (len-dex) were combined with escalating doses of AZA from 30mg/m2 SC weekly to 50mg/m2SC twice a week. Dose limiting toxicity (DLT) was assessed during cycle 1. IMWG uniform response criteria (partial response, PR) and adapted EBMT criteria (minor response, MR) were used. Plasma activity of the AZA inactivating enzyme cytidine deaminase (CDA) was measured by HPLC at Zymo Research Corp., CA. Results: Forty patients (pts) with relapsed (n = 3) or refractory (n = 37) MM were enrolled after a median of 4 prior regimens (range 1-10). Their disease was refractory to len (n = 32), bortezomib and / or carfilzomib (n = 32), or both len and proteasome inhibitors (n = 28). The target phase II dose of 50mg/m2 SC twice a wk was reached. One DLT (neutropenic fever without documented infection) occurred in 1 of 6 pts treated with 40mg/m2 AZA twice a week);. Grade 3/ 4 toxicities possibly drug related were seen in 23 pts (58%), neutropenia (13), thrombocytopenia (5), fatigue (3), infection (2), anemia (2), pleural effusion (1), fever (1), and atrial fibrillation (1). Twelve pts achieved > MR, 9 > PR (3 VGPR) yielding 30% clinical benefit response (CBR) and 22.5% response rates. Median time on study was 90 days. Responses lasted between 3 months and 2 years. Five pts remain on study. Plasma CDA activity at screening and during the study (q wk x4, then q 28d) inversely correlated with achieving > MR (p < 0.03, p < 0.01, respectively, Wilcoxon exact test) and varied by median 17%. Pts with screening CDA activity < 1000 mU/mL had 50% CBR, vs. 21% if > 1000mU/mL. Conclusions: AZA was well tolerated up to target 50mg/m2 SC twice a week in combination with len-dex . Inverse correlation of CDA activity with response suggests AZA contributed to benefit and supports development of the HPLC assay to select patients for aza nucleoside treatment and guide development of CDA inhibitors. Clinical trial information: NCT01155583.
Abstract 18065: Prospective Evaluation of a Genetic Risk Score for Atrial Fibrillation in Patients Undergoing Extended Cardiac Rhythm Monitoring
Authors: Evan D Muse, Emily G Spencer, Nathan E Wineinger, Melissa Peters, Paddy Barrett, Steven P Rivera, Jay G Wohlgemuth, James J Devlin, Dov X Shiffman, Eric J Topol
Journal: Circulation (2016)

Introduction: Atrial fibrillation (AF) is the most commonly encountered arrhythmia. AF is associated with elevated risk of stroke. Thus, it is critical to accurately identify patients at the highes...
Large-scale pharmacogenomics based drug discovery for ITGB3 dependent chemoresistance in mesenchymal lung cancer
Authors: Soon-Ki Hong, Haeseung Lee, Ok-Seon Kwon, Na-Young Song, Hyo-Ju Lee, Seungmin Kang, Jeong-Hwan Kim, Mirang Kim, Wankyu Kim, Hyuk-Jin Cha
Journal: Molecular Cancer (2018)

Even when targets responsible for chemoresistance are identified, drug development is often hampered due to the poor druggability of these proteins. We systematically analyzed therapy-resistance with a large-scale cancer cell transcriptome and drug-response datasets and predicted the candidate drugs based on the gene expression profile. Our results implicated the epithelial–mesenchymal transition as a common mechanism underlying resistance to chemotherapeutic drugs. Notably, we identified ITGB3, whose expression was abundant in both drug resistance and mesenchymal status, as a promising target to overcome chemoresistance. We also confirmed that depletion of ITGB3 sensitized cancer cells to conventional chemotherapeutic drugs by modulating the NF-κB signaling pathway. Considering the poor druggability of ITGB3 and the lack of feasible drugs to directly inhibit this protein, we took an in silico screening for drugs mimicking the transcriptome-level changes caused by knockdown of ITGB3. This approach successfully identified atorvastatin as a novel candidate for drug repurposing, paving an alternative path to drug screening that is applicable to undruggable targets.
Erratum: Correlation of pharmacological 99mTc-sestamibi myocardial perfusion imaging with poststenotic coronary flow reserve in patients with angiographically intermediate coronary artery stenoses (Circulation (1994) 89 (2150-2160))
Authors: Donald D Miller, T. J. Donohue, L. T. Younis, R. G. Bach, F. V. Aguirre, M. D. Wittry, H. M. Goodgold, B. R. Chaitman, M. J. Kern
Journal: Circulation (1994)
Life expectancy: preventing heart disease will do most to reduce disparities, report finds
Authors: Nigel Hawkes
Journal: BMJ (2018)

No single cause can be found for the slowdown in life expectancy improvement seen in the UK, a report from Public Health England (PHE) has concluded.1

It does not rule out the belt tightening in health and social care that began in 2011 and has coincided with higher mortality and a life expectancy slowdown, but neither does it give this the prominence accorded by some commentators.

The report concludes that slowing improvements in heart disease and stroke, high winter mortality from flu in several recent years, the growth of dementia as a recorded cause of death, and more deaths from drug misuse among younger people have all played a part.

Similar trends in mortality and life expectancy have been seen throughout Europe and the US over the same period, so a UK specific explanation is unlikely to be correct. But the trends visible everywhere are more pronounced in the UK, which showed the lowest rate of improvement among all large EU countries …
Remissions in Relapse/Refractory Acute Myeloid Leukemia Patients Following Treatment with NKG2D CAR-T Therapy without a Prior Preconditioning Chemotherapy
Authors: David A Sallman, Tessa Kerre, Xavier Poire, Violaine Havelange, Philippe Lewalle, Marco L. Davila, Eunice S. Wang, Doreen Dekker, Sarah Snykers, Panagiota A. Sotiropoulou, Eytan Breman, Nathalie Braun, Caroline Lonez, Bikash Verma, Frédéric F. Lehmann, Jason B. Brayer
Journal: Blood (2018)
Reply to Moodley and to Ravaglia <i>et al.</i>
Authors: Ganesh Raghu, Martine Remy-Jardin, Jeffrey L. Myers, Luca Richeldi, Kevin Wilson
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Comment on Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. [Am J Respir Crit Care Med. 2018] New Idiopathic Pulmonary Fibrosis Guidelines: Are Cryobiopsy and Surgery Competitive in Clinical Practice? [Am J Respir Crit Care Med. 2019] Considerations in the Diagnosis of Idiopathic Pulmonary Fibrosis. [Am J Respir Crit Care Med. 2019]
LncHOXA10 drives liver TICs self-renewal and tumorigenesis via HOXA10 transcription activation
Authors: Ming Shao, Qiankun Yang, Weitao Zhu, Huifang Jin, Jing Wang, Jie Song, Yongkui Kong, Xianping Lv
Journal: Molecular Cancer (2018)

Liver cancer is one of the most deadly cancers in the world. There are various cells in liver tumor bulk, including liver tumor initiating cells (TICs), which account for liver tumorigenesis, drug resistance, relapse and metastasis. The homeobox (HOX) transcription factors play critical roles in many physiological and pathological processes, while, their roles in liver TICs and liver tumorigenesis remain unknown. An unbiased screening was performed using online-available datasets. Liver TICs were sorted by FACS using surface markers CD133, CD13 and EPCAM, or enriched by oncosphere formation assay. TIC self-renewal was examined by oncosphere formation and tumor initiation assay. Loss of function and gain of function assays were performed to examine the role of lncRNA. RNA pulldown, RNA immunoprecipitation, ChIP, Western blot and double FISH were used to explore the molecular mechanism of lncRNA. Here, we examined the expression pattern of HOX transcription factors, and found HOXA10 was overexpressed in liver cancer samples. Moreover, a divergent lncRNA of HOXA10 (termed lncHOXA10 hereafter) was also highly expressed in liver cancer and liver TICs. LncHOXA10 drove liver TIC self-renewal and liver tumorigenesis through HOXA10-dependent manner. LncHOXA10 interacted with SNF2L and recruited NURF chromatin remodeling complex to HOXA10 promoter, and thus initiated the transcription of HOXA10. Through HOXA10 transcriptional regulation, lncHOXA10 activated HOXA10 in liver TICs. LncHOXA10-HOXA10 signaling can be targeted to eliminate liver TICs. Altogether, lncHOXA10 drove HOXA10 expression and thus promoted liver TIC self-renewal. HOXA10 was the most highly expressed HOX transcription factor in liver cancer and liver TICs. LncHOXA10 drove the transcriptional activation of HOXA10. This work revealed the important role of HOX transcription factor in liver TIC self-renewal and added a new layer for liver TIC regulation.
Abstract 14127: Measures of Patient Activation and Social Support in a Peer-led Support Network for Women With CVD
Authors: Dawn Witt, Gretchen Benson, Arthur Sillah, Susan Campbell, Kathy Berra
Journal: Circulation (2015)

Introduction: Social support has been recognized as having a strong impact on health and well-being and has also been shown to have beneficial effects in a wide variety of disease states. Social support from friends, family or peers can augment the care offered in traditional healthcare settings by providing advice, encouragement and education However, there is limited research on the impact of peer-led support programs among women living with cardiovascular disease (CVD). Objective: To examine the relationship between patient activation and measures of social support among women who attended a WomenHeart: The National Coalition for Women with Heart Disease peer-led support program in their local community. We hypothesized that high levels of social support would be associated with high levels of patient activation in this study population. Methods: Participants were recruited from 50 national WomenHeart Support Network groups. A 70 item, online survey was administered and the main analytic sample for this study included 157 women. Multivariable logistic regression was used to examine the association between patient activation levels (Lower activation levels: 1,2 vs higher activation levels: 3,4) and social support scores (range: lowest 8 to highest 34), adjusting for age. Results: Study participants reported high levels of social support and patient activation. Those who were at or above the median for the social support measures (indicating high levels of social support) had greater odds of high levels of patient activation (levels 3 or 4) compared to individuals reporting low levels of social support (OR 2.23 95%CI1.04, 4.76, p = 0.012). Conclusions: Results of our survey demonstrate that this group of women with coronary heart disease who regularly attended a peer-led support group and indicated a high level of social support report taking a more active role in self-management behaviors.
Increased Methylation of Deamidated Asparagines and Aspartates in Stored Red Blood Cells from Glucose 6-Phosphate Dehydrogenase-Deficient Blood Donors
Authors: Angelo D'Alessandro, Travis Nemkov, Julie Reisz, Monika Dzieciatkowska, Rachel Culp-Hill, Davide Stefanoni, Tatsuro Yoshida, Andrew Dunham, Tamir Kanias, Larry J. DuMont, Michael Paul Busch, Elan Z Eisenmesser, Kirk C Hansen, Xiaoyun Fu, Tiffany Thomas, Matthew Karafin, Eldad A. Hod, Richard O Francis, Steven L Spitalnik, James C. Zimring
Journal: Blood (2018)
Combined analysis of retrospective and prospective studies to evaluate the significance of FCα receptor polymorphisms in response to cetuximab plus irinotecan therapy for chemorefractory Japanese patients with advanced and/or metastatic colorectal cancer.
Authors: Hideki Shimodaira, Hiroshi Soeda, Keigo Komine, Masahiro Inoue, Masanobu Takahashi, Shin Takahashi, Mika Watanabe, Shunsuke Kato, Makio Gamoh, Chikashi Ishioka
Journal: Journal of Clinical Oncology (2014)

e14582 Background: Polymorphisms in the Fcγ receptor genes is a potentially predictive biomarker for efficacy to Anti-EGFR antibody treatment. However, this was not fully established by the controversial results of Caucasian studies. Moreover, there are few studies for Japanese on the allele frequency of Fcγ receptor polymorphisms and relationship with the clinical outcome of anti-EGFR antibody treatment. Then, this combined analysis of prospective and retrospective studies investigated the role of Fcγ receptor genes on efficacy and safety to cetuximab plus irinotecan in Japanese patients with metastatic colorectal cancer (mCRC). Methods: We conducted studies to analyze objective response rate (RR) and progression free survival (PFS) to cetuximab plus irinotecan in chemotherapy-refractory 79 patients with mCRC. KRAS, BRAF, PIK3CA, NRAS and AKT1 mutations were detected by direct sequence on DNA from formalin-fixed, paraffin-embedded tissue of patients treated in 11 centers in Japan. Polymorphism in FCγRIIa and RIIIa genes were also examined in the normal tissue by the same method. To analyze the allele frequency of FCγRIIa and RIIIa polymorphisms, 184 mCRC patients were examined regardless treatments Results: Among 184 Japanese mCRC patients, FCγRIIa H/H (57.6%), FCγRIIIa F/F (51.1%) were most frequent in contrast to Caucasian who have high frequency in FCγRIIa H/R and FCγRIIIa V/F. Among 56 patients with KRAS wild-type tumor treated by cetuximab, there was no significant deference in the PFS between FCγRIIa H/H group and H/R+R/R (PFS; 5.1 M vs. 3.1 M, P=0.14). However, FCγRIIIa V/V+V/F group showed longer PFS than FCγRIIIa F/F group (6.2 M vs. 3.5 M, P=0.044) Conclusions: There is deference allele frequency of Fcγ receptor genes between Japanese and Caucasian. In Japanese chemo-refractory mCRC patients, FCγRIIIa V/V+V/F group showed longer PFS than FCγRIIIa F/F group in cetuximab based therapy. Clinical trial information: UMIN000004298.
Architectural Design of 3D Printed Scaffolds Controls the Volume and Functionality of Newly Formed Bone
Authors: Ali Entezari, Iman Roohani, Guanglong Li, Colin R. Dunstan, Pierre Rognon, Qing Li, Xinquan Jiang, Hala Zreiqat
Journal: Advanced Healthcare Materials (2018)

The successful regeneration of functional bone tissue in critical-size defects remains a significant clinical challenge. To address this challenge, synthetic bone scaffolds are widely developed, but remarkably few are translated to the clinic due to poor performance in vivo. Here, it is demonstrated how architectural design of 3D printed scaffolds can improve in vivo outcomes. Ceramic scaffolds with different pore sizes and permeabilities, but with similar porosity and interconnectivity, are implanted in rabbit calvaria for 12 weeks, and then the explants are harvested for microcomputed tomography evaluation of the volume and functionality of newly formed bone. The results indicate that scaffold pores should be larger than 390 µm with an upper limit of 590 µm to enhance bone formation. It is also demonstrated that a bimodal pore topology-alternating large and small pores-enhances the volume and functionality of new bone substantially. Moreover, bone formation results indicate that stiffness of new bone is highly influenced by the scaffold's permeability in the direction concerned. This study demonstrates that manipulating pore size and permeability in a 3D printed scaffold architecture provides a useful strategy for enhancing bone regeneration outcomes.
Targeting the CD40-CD40L pathway in autoimmune diseases: Humoral immunity and beyond
Authors: Jodi L. Karnell, Sadiye Amcaoglu Rieder, Rachel Ettinger, Roland Kolbeck
Journal: Advanced Drug Delivery Reviews (2018)

CD40 is a TNF receptor superfamily member expressed on both immune and non-immune cells. Interactions between B cell-expressed CD40 and its binding partner, CD40L, predominantly expressed on activated CD4+ T cells, play a critical role in promoting germinal center formation and the production of class-switched antibodies. Non-hematopoietic cells expressing CD40 can also engage CD40L and trigger a pro-inflammatory response. This article will highlight what is known about the biology of the CD40-CD40L axis in humans and describe the potential contribution of CD40 signaling on both hematopoietic and non-hematopoietic cells to autoimmune disease pathogenesis. Additionally, novel therapeutic approaches to target this pathway, currently being evaluated in clinical trials, are discussed.
Trends in Firearm Injury and Motor Vehicle Crash Case Fatality by Age Group, 2003-2013
Authors: Robert A. Tessler, Saman Arbabi, Eileen M. Bulger, Brianna Mills, Frederick P. Rivara
Journal: JAMA Surgery (2018)

If changes over time in trauma care apply to both firearm injuries and motor vehicle crashes (MVCs) similarly, differences in mechanism-specific case-fatality trends may suggest changes over time in injury severity.To analyze national trends in case-fatality percentages at levels I and II trauma centers for injuries due to MVC, firearm assault, self-inflicted firearm injury, and unintentional firearm injury by age and to analyze trends in injury severity scores (ISSs) and the percentage of out-of-hospital deaths by mechanism.From November 15, 2017, to July 4, 2018, repeated cross-sectional measures analysis of 1 335 044 patients treated at level I or II trauma centers from January 1, 2003, through December 31, 2013, was conducted using 2 data sources: the National Trauma Data Bank National Sample Program, with survey weights to estimate annual median ISS, total injuries and total deaths at levels I and II trauma centers, and the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research for percentages of out-of-hospital deaths.The main outcome was annual case-fatality percentage (total died/total injured), calculated by mechanism across 3 age groups (15-34 years, 35-54 years, and ≥55 years) and 5 categories of ISS (1-15 [mild] 16-24, 25-40, 41-66, and 67-75 [severe]). Linear regression was performed to estimate annual trends in case-fatality percentage by mechanism, age group, and ISS. Annual trends in percentages of out-of-hospital deaths and median ISSs by mechanism were estimated. Sensitivity analyses included the Durbin-Watson statistic for autocorrelation and Prais-Winsten regression models.Among 1 335 044 patients treated at level I or II trauma centers, self-inflicted firearm injury had a case-fatality percentage of 42.8%, and assault with a firearm had a case-fatality percentage of 11.1%, the 2 highest of the injuries studied. The injury case-fatality percentage was lower each year for MVCs but did not change for any firearm intent overall or for any age group. Overall, median ISS increased annually for firearm suicide (0.31; 95% CI, 0.00-0.61). The annual percentage of out-of-hospital deaths was lower each year for MVCs (-0.24; 95% CI, -0.43 to -0.05) but not for any firearm intents. In sensitivity analyses, the annual percentage of out-of-hospital deaths for MVCs no longer showed a decline.Stagnant case-fatality percentages for firearm injuries juxtaposed to improvements for MVCs across age-groups and ISS categories suggests worsening severity of firearm injuries over the study period.
Enhancing the Accumulation of Polymer Micelles by Selectively Dilating Tumor Blood Vessels with NO for Highly Effective Cancer Treatment
Authors: Guoqing Wei, Yi Wang, Xuehui Huang, Guang Yang, Jingya Zhao, Shaobing Zhou
Journal: Advanced Healthcare Materials (2018)

Abstract The accumulation of nanoparticles in tumors by the enhanced permeability and retention (EPR) effect is effective and well known. However, how to maximize accumulation is still a bottleneck in the development of nanomedicine. Herein, a tumor vascular‐targeted hybrid polymeric micelle, which has a great capacity to selectively augment the EPR effect of nanoparticles by dilating tumor blood vessels via the activity of nitric oxide (NO), is presented. Under neutral conditions, the micelle is stable, with a long blood circulation half‐life due to the carboxylated poly(ethylene glycol) (PEG) layer; in mildly acidic tumor tissues, the micelle can selectively target the tumor blood vessels by the exposed cyclic Arg‐Gly‐Asp peptide (cRGD) peptides, which is realized with a pH‐dependent hydrolysis of the monomethoxy PEG layer. Simultaneously, exposed copper ions catalyze the decomposition of endogenous NO donors, which generates NO in situ, leading to vasodilation and increased tumor vascular permeability. As a result, the accumulation of nanoparticles is significantly enhanced, and a high accumulation of doxorubicin in tumors is achieved at 48 h after injection. This high dose of therapeutic agent produces a large inhibition of tumor growth (94%) in cancer treatment, and shows no general toxicity, with 100% of the mice surviving the treatment regimen.