tbuckley/cabot-search huggingface dataset:
Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity: Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up
Authors: Sandra Lockmer, Bjørn Østenstad, Hans Hagberg, Harald Holte, Ann-Sofie Johansson, Björn Engelbrekt Wahlin, Karin Fahl Wader, Chloé Beate Steen, Peter Meyer, Martin Maisenhølder, Karin Ekström Smedby, Peter Brown, Eva Kimby
Journal: Journal of Clinical Oncology (2018)

For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies.
Abstract 17778: Quantifying the Value of Drone-Delivered Automated External Defibrillators in Cardiac Arrest Response
Authors: Justin J Boutilier, Steven C Brooks, Alyf Janmohamed, Adam Byers, Cathy Zhan, Jason E Buick, Angela P Schoellig, Laurie J Morrison, Sheldon Cheskes, Timothy C Chan
Journal: Circulation (2016)

Background: Public access defibrillation programs can improve survival after OHCA, but AEDs are rarely available for bystander use at the scene. Drones are an emerging technology that can deliver a...
Maximizing Data Transmission Rate for Implantable Devices Over a Single Inductive Link: Methodological Review
Authors: Aref Trigui, Sami Hached, Ahmed Chiheb Ammari, Yvon Savaria, Mohamad Sawan
Journal: IEEE Reviews in Biomedical Engineering (2018)

Due to the constantly growing geriatric population and the projected increase of the prevalence of chronic diseases that are refractory to drugs, implantable medical devices (IMDs) such as neurostimulators, endoscopic capsules, artificial retinal prostheses, and brain-machine interfaces are being developed. According to many business forecast firms, the IMD market is expected to grow and they are subject to much research aiming to overcome the numerous challenges of their development. One of these challenges consists of designing a wireless power and data transmission system that has high power efficiency, high data rates, low power consumption, and high robustness against noise. This is in addition to minimal design and implementation complexity. This manuscript concerns a comprehensive survey of the latest techniques used to power up and communicate between an external base station and an IMD. Patient safety considerations related to biological, physical, electromagnetic, and electromagnetic interference concerns for wireless IMDs are also explored. The simultaneous powering and data communication techniques using a single inductive link for both power transfer and bidirectional data communication, including the various data modulation/demodulation techniques, are also reviewed. This review will hopefully contribute to the persistent efforts to implement compact reliable IMDs while lowering their cost and upsurging their benefits.
Challenges in assessing the burden of sepsis and understanding the inequalities of sepsis outcomes between National Health Systems: secular trends in sepsis and infection incidence and mortality in Germany
Authors: C. Fleischmann-Struzek, A. Mikolajetz, D. Schwarzkopf, J. Cohen, C. S. Hartog, M. Pletz, P. Gastmeier, K. Reinhart
Journal: Intensive Care Medicine (2018)

Sepsis contributes considerably to global morbidity and mortality, while reasons for its increasing incidence remain unclear. We assessed risk adjusted secular trends in sepsis and infection epidemiology in Germany.Retrospective cohort study using nationwide German hospital discharge data. We assessed incidence, outcomes and trends of hospital-treated sepsis and infections between 2010 and 2015. Sepsis was identified by explicit ICD-10 sepsis codes. As sensitivity analysis, results were compared with sepsis cases identified by implicit sepsis coding (combined infection and organ dysfunction codes).Among 18 664 877 hospital admissions in 2015, 4 213 116 (22.6%) patients had at least one infection code. There were 320 198 patients that had explicit sepsis codes including 136 542 patients with severe sepsis and septic shock; 183 656 patients were coded as sepsis without organ dysfunction. For patients with explicitly coded sepsis (including severe sepsis), or with severe sepsis alone, mortality rates over the period 2010-2015 decreased from 26.6 to 23.5%, and from 47.8 to 41.7%, respectively.Sepsis and infection remain significant causes of hospital admission and death in Germany. Sepsis-related mortality is higher and has declined to a lesser degree than in other high-income countries. Although infection rates steadily increased, the observed annual increase of sepsis cases seems to result, to a considerable degree, from improved coding of sepsis.
A new ALK isoform transported by extracellular vesicles confers drug resistance to melanoma cells
Authors: Giulia Cesi, Demetra Philippidou, Ines Kozar, Yeoun Jin Kim, Francois Bernardin, Guillaume Van Niel, Anke Wienecke-Baldacchino, Paul Felten, Elisabeth Letellier, Sonja Dengler, Dorothee Nashan, Claude Haan, Stephanie Kreis
Journal: Molecular Cancer (2018)

Drug resistance remains an unsolved clinical issue in oncology. Despite promising initial responses obtained with BRAF and MEK kinase inhibitors, resistance to treatment develops within months in virtually all melanoma patients. Microarray analyses were performed in BRAF inhibitor-sensitive and resistant cell lines to identify changes in the transcriptome that might play a role in resistance. siRNA approaches and kinase inhibitors were used to assess the involvement of the identified Anaplastic Lymphoma Kinase (ALK) in drug resistance. The capability of extracellular vesicles (EVs) to transfer drug resistant properties was investigated in co-culture assays. Here, we report a new mechanism of acquired drug resistance involving the activation of a novel truncated form of ALK. Knock down or inhibition of ALK re-sensitised resistant cells to BRAF inhibition and induced apoptosis. Interestingly, truncated ALK was also secreted into EVs and we show that EVs were the vehicle for transferring drug resistance. To our knowledge, this is the first report demonstrating the functional involvement of EVs in melanoma drug resistance by transporting a truncated but functional form of ALK, able to activate the MAPK signalling pathway in target cells. Combined inhibition of ALK and BRAF dramatically reduced tumour growth in vivo. These findings make ALK a promising clinical target in melanoma patients.
Abstract 15776: Longitudinal to Circumferential Diastolic Dyssynchrony in Heart Failure With Preserved Ejection Fraction and its Relationship to Myocardial Fibrosis
Authors: Julio A Chirinos, Haideliza Soto-Calderon, Swapna Varakantam, Amer Ahmed Syed, Timothy S Phan, Maheswara R Koppula, Uzma Kewan, Ejaz Shah, Scott R Akers
Journal: Circulation (2016)

Background: Diastolic dysfunction is a prominent feature of Heart Failure with Preserved Ejection Fraction (HFpEF). The basis of abnormal diastolic function in HFpEF is incompletely understood. We ...
Gene Expression Profiling Reveals Aberrant T-cell Marker Expression on Tumor Cells of Waldenström's Macroglobulinemia
Authors: Mu Hao, Bart Barlogie, Guido Tricot, Lanting Liu, Lugui Qiu, John D. Shaughnessy, Fenghuang Zhan
Journal: Clinical Cancer Research (2018)

That the malignant clone of Waldenström's macroglobulinemia (WM) demonstrates significant intraclonal heterogeneity with respect to plasmacytoid differentiation indicates the mechanistic complexity of tumorigenesis and progression. Identification of WM genes by comparing different stages of B cells may provide novel druggable targets.The gene expression signatures of CD19+ B cells (BC) and CD138+ plasma cells (PC) from 19 patients with WM were compared with those of BCs from peripheral blood and tonsil and to those of PCs from the marrow of healthy (N-PC) and multiple myeloma donors (MM-PC), as well as tonsil (T-PC). Flow cytometry and immunofluorescence were used to examine T-cell marker expression on WM tumor cells.Consistent with defective differentiation, both BCs and PCs from WM cases expressed abnormal differentiation markers. Sets of 55 and 46 genes were differentially expressed in WM-BC and WM-PC, respectively; and 40 genes uniquely dysregulated in WM samples were identified. Dysregulated genes included cytokines, growth factor receptors, and oncogenes not previously implicated in WM or other plasma cell dyscrasias. Interestingly, strong upregulation of both IL6 and IL6R was confirmed. Supervised cluster analysis of PC revealed that marrow-derived WM-PC was either MM-PC-like or T-PC-like, but not N-PC-like. The aberrant expression of T-cell markers was confirmed at the protein level in WM-BC.We showed that comparative microarray profiles allowed gaining more comprehensive insights into the biology of WM. The data presented here have implications for the development of novel therapies, such as targeting aberrant T-cell markers in WM.
Abstract 19942: Underdiagnosis and Undertreatment of Heterozygous Familial Hypercholesterolemia in Association With Cardiovascular Disease
Authors: Haruki Sekiguchi, Takuro Abe, Jihaeng Imu, Mayu Takano, Makiko Kimura, Issei Ishida, Akiko Sakai, Kayoko Sato, Nobuhisa Hagiwara
Journal: Circulation (2017)

Introduction: Heterozygous familial hypercholesterolemia (hFH) is a common genetic disease that causes premature coronary heart disease. However, the rate of diagnosis in Japan is less than 0.1%. A...
Abstract 20573: Influence of Preoperative Comorbidities on Long-Term Survival After Aortic Arch Replacement
Authors: Mauro Iafrancesco, Aaron Ranasinghe, Paul Clift, Martin Claridge, Donald Adam, Ian McCafferty, Peter Riley, Jorge Mascaro
Journal: Circulation (2017)

Introduction: Aortic arch replacement (AAR) is a complex operation with significant operative risk usually performed on prognostic grounds. There is limited evidence regarding the impact of preoperative comorbidities on long-term survival after open AAR Hypothesis: We reviewed our experience with open AAR to try to identify those patients who may benefit more from surgical intervention and those who may not. Methods: From January 1999 to December 2012, 272 patients underwent total AAR at our Institution. Patients were divided in groups according to the number of major comorbidities (chronic renal failure, peripheral vascular disease, chronic obstructive pulmonary disease, history of neurological disease, coronary artery disease) of each patient and long-term survival compared among groups. Results: Surgical mortality was 8.1% for the entire population and 0%, 7.5%, 5.8%, 16.7% and 33.3% for patients with 0, 1, 2, 3 and 4/5 comorbidities, respectively. Mean follow-up was 55 months (100% complete). There wa...
ΔNp63-driven recruitment of myeloid-derived suppressor cells promotes metastasis in triple-negative breast cancer
Authors: Sushil Kumar, David W. Wilkes, Nina Samuel, Mario Andres Blanco, Anupma Nayak, Kevin Alicea-Torres, Christian Gluck, Satrajit Sinha, Dmitry Gabrilovich, Rumela Chakrabarti
Journal: Journal of Clinical Investigation (2018)

Triple-negative breast cancer (TNBC) is particularly aggressive, with enhanced incidence of tumor relapse, resistance to chemotherapy, and metastases. As the mechanistic basis for this aggressive phenotype is unclear, treatment options are limited. Here, we showed an increased population of myeloid-derived immunosuppressor cells (MDSCs) in TNBC patients compared with non-TNBC patients. We found that high levels of the transcription factor ΔNp63 correlate with an increased number of MDSCs in basal TNBC patients, and that ΔNp63 promotes tumor growth, progression, and metastasis in human and mouse TNBC cells. Furthermore, we showed that MDSC recruitment to the primary tumor and metastatic sites occurs via direct ΔNp63-dependent activation of the chemokines CXCL2 and CCL22. CXCR2/CCR4 inhibitors reduced MDSC recruitment, angiogenesis, and metastasis, highlighting a novel treatment option for this subset of TNBC patients. Finally, we found that MDSCs secrete prometastatic factors such as MMP9 and chitinase 3–like 1 to promote TNBC cancer stem cell function, thereby identifying a nonimmunologic role for MDSCs in promoting TNBC progression. These findings identify a unique crosstalk between ΔNp63+ TNBC cells and MDSCs that promotes tumor progression and metastasis, which could be exploited in future combined immunotherapy/chemotherapy strategies for TNBC patients.
Publisher Correction: Genomes of 13 domesticated and wild rice relatives highlight genetic conservation, turnover and innovation across the genus Oryza
Authors: Joshua C. Stein, Yeisoo Yu, Dario Copetti, Derrick J. Zwickl, Li Zhang, Chengjun Zhang, Kapeel Chougule, Dongying Gao, Aiko Iwata, Jose Luis Goicoechea, Sharon Wei, Jun Wang, Yi Liao, Muhua Wang, Julie Jacquemin, Claude Becker, Dave Kudrna, Jianwei Zhang, Carlos E. M. Londono, Xiang Song, Seunghee Lee, Paul Sanchez, Andrea Zuccolo, Jetty S. S. Ammiraju, Jayson Talag, Ann Danowitz, Luis F. Rivera, Andrea R. Gschwend, Christos Noutsos, Cheng-chieh Wu, Shu-min Kao, Jhih-wun Zeng, Fu-jin Wei, Qiang Zhao, Qi Feng, Moaine El Baidouri, Marie-Christine Carpentier, Eric Lasserre, Richard Cooke, Daniel da Rosa Farias, Luciano Carlos da Maia, Railson S. dos Santos, Kevin G. Nyberg, Kenneth L. McNally, Ramil Mauleon, Nickolai Alexandrov, Jeremy Schmutz, Dave Flowers, Chuanzhu Fan, Detlef Weigel, Kshirod K. Jena, Thomas Wicker, Mingsheng Chen, Bin Han, Robert Henry, Yue-ie C. Hsing, Nori Kurata, Antonio Costa de Oliveira, Olivier Panaud, Scott A. Jackson, Carlos A. Machado, Michael J. Sanderson, Manyuan Long, Doreen Ware, Rod A. Wing
Journal: Nature Genetics (2018)
Abstract 14139: Therapy With Sacubitril/Valsartan Improves Left Ventricular Systolic Function and Biomarkers of Kidney Injury in Dogs With Experimentally-Induced Cardiorenal Syndrome
Authors: Hani N Sabbah, Kefei Zhang, Jiang Xu, Ramesh C Gupta, Vinita Singh-Gupta
Journal: Circulation (2017)

Introduction: Sacubitril/Valsartan (S/Val) is a combined angiotensin-II receptor blocker (Val) and neprilysin inhibitor (S) in a 1:1 molar ratio. S/Val was shown to reduce the risk of cardiovascula...
Increased Activity Due to Fractures Does Not Significantly Affect the Accuracy of 68Ga-DOTATATE PET/CT in the Detection of Culprit Tumor in the Evaluation of Tumor-Induced Osteomalacia
Authors: Jie Ding, Guilan Hu, Ling Wang, Fang Li, Li Huo
Journal: Clinical Nuclear Medicine (2018)

Ga-DOTATATE PET/CT is currently the most common imaging modality in localizing culprit tumors, which can result in tumor-induced osteomalacia (TIO). Fracture, which is one of the most common consequences of the TIO, can also lead to increased Ga-DOTATATE activity and potentially affect the accuracy of Ga-DOTATATE PET/CT imaging. The aim of this investigation is to evaluate whether the increased Ga-DOTATATE activity at the sites of the fracture will cause interpretation difficulty in the localizing the culprit tumor causing TIO.The images of Ga-DOTATATE PET/CT scan from a total of 54 patients who had multiple foci of increased Ga-DOTATATE PET/CT on PET/CT were retrospectively analyzed. Not only was the intensity of the activity on PET but also the appearance of the activity on CT taken into consideration when the interpretation of the images occurred. The results from imaging analysis were compared with the clinical chart record. All patients had tentative clinical diagnosis of TIO.The causative tumors in 53 patients were eventually identified. In 1 patient, the causative tumor was not identified. Among the 53 patients with confirmed TIO, 52 tumors were accurately localized.Mild activity at the sites of fracture is not a major challenging factor in the interpretation of Ga-DOTATATE PET/CT in the evaluation of TIO when both intensity on PET and morphology on CT were assessed.
Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival
Authors: Baharak Bahmani, Mayuko Uehara, Liwei Jiang, Farideh Ordikhani, Naima Banouni, Takaharu Ichimura, Zhabiz Solhjou, Georg J. Furtmüller, Gerald Brandacher, David Alvarez, Ulrich H. von Andrian, Kenji Uchimura, Qiaobing Xu, Ishaan Vohra, Osman A. Yilmam, Yousef Haik, Jamil Azzi, Vivek Kasinath, Jonathan S. Bromberg, Martina M. McGrath, Reza Abdi
Journal: Journal of Clinical Investigation (2018)

The targeted delivery of therapeutic drugs to lymph nodes (LNs) provides an unprecedented opportunity to improve the outcomes of transplantation and immune-mediated diseases. The high endothelial venule is a specialized segment of LN vasculature that uniquely expresses peripheral node addressin (PNAd) molecules. PNAd is recognized by MECA79 mAb. We previously generated a MECA79 mAb–coated microparticle (MP) that carries tacrolimus. Although this MP trafficked to LNs, it demonstrated limited therapeutic efficacy in our transplant model. Here, we have synthesized a nanoparticle (NP) as a carrier of anti-CD3, and optimized the conjugation strategy to coat the NP surface with MECA79 mAb (MECA79-anti-CD3-NP) to enhance LN accumulation. As compared with nonconjugated NPs, a significantly higher quantity of MECA79-NPs accumulated in the draining lymph node (DLN). Many MECA79-NPs underwent internalization by T cells and dendritic cells within the LNs. Short-term treatment of murine cardiac allograft recipients with MECA79-anti-CD3-NP resulted in significantly prolonged allograft survival in comparison with the control groups. Prolonged graft survival following treatment with MECA79-anti-CD3-NP was characterized by a significant increase in intragraft and DLN Treg populations. Treg depletion abrogated the prolongation of heart allograft survival. We believe this targeted approach of drug delivery could redefine the methods of administering immune therapeutics in transplantation.
SOX4 controls invariant NKT cell differentiation by tuning TCR signaling
Authors: Nidhi Malhotra, Yilin Qi, Nicholas A. Spidale, Michela Frascoli, Bing Miu, Okhyun Cho, Katelyn Sylvia, Joonsoo Kang
Journal: The Journal of Experimental Medicine (2018)

Natural killer T (NKT) cells expressing the invariant T cell receptor (iTCR) serve an essential function in clearance of certain pathogens and have been implicated in autoimmune and allergic diseases. Complex effector programs of these iNKT cells are wired in the thymus, and upon thymic egress, they can respond within hours of antigenic challenges, classifying iNKT cells as innate-like. It has been assumed that the successful rearrangement of the invariant iTCRα chain is the central event in the divergence of immature thymocytes to the NKT cell lineage, but molecular properties that render the iTCR signaling distinct to permit the T cell lineage diversification remain obscure. Here we show that the High Mobility Group (HMG) transcription factor (TF) SOX4 controls the production of iNKT cells by inducing MicroRNA-181 (Mir181) to enhance TCR signaling and Ca2+ fluxes in precursors. These results suggest the existence of tailored, permissive gene circuits in iNKT precursors for innate-like T cell development.
Does Radial Artery Harvest for Coronary Surgery Compromise Forearm Blood Flow to 22 Years Post-Operative?
Authors: Alistair G. Royse, Megan J. O’Donnell, Laura Mocioaca, Varun Sharma, Jared C. Ou-Young, David J. Canty, Colin F. Royse
Journal: Journal of the American College of Cardiology (2018)
Remodeling of the Collagen Matrix in Aging Skin Promotes Melanoma Metastasis and Affects Immune Cell Motility
Authors: Amanpreet Kaur, Brett L. Ecker, Stephen M. Douglass, Curtis H. Kugel, Marie R. Webster, Filipe V. Almeida, Rajasekharan Somasundaram, James Hayden, Ehsan Ban, Hossein Ahmadzadeh, Janusz Franco-Barraza, Neelima Shah, Ian A. Mellis, Frederick Keeney, Andrew Kossenkov, Hsin-Yao Tang, Xiangfan Yin, Qin Liu, Xiaowei Xu, Mitchell Fane, Patricia Brafford, Meenhard Herlyn, David W. Speicher, Jennifer A. Wargo, Michael T. Tetzlaff, Lauren E. Haydu, Arjun Raj, Vivek Shenoy, Edna Cukierman, Ashani T. Weeraratna
Journal: Cancer Discovery (2018)

Abstract Physical changes in skin are among the most visible signs of aging. We found that young dermal fibroblasts secrete high levels of extracellular matrix (ECM) constituents, including proteoglycans, glycoproteins, and cartilage-linking proteins. The most abundantly secreted was HAPLN1, a hyaluronic and proteoglycan link protein. HAPLN1 was lost in aged fibroblasts, resulting in a more aligned ECM that promoted metastasis of melanoma cells. Reconstituting HAPLN1 inhibited metastasis in an aged microenvironment, in 3-D skin reconstruction models, and in vivo. Intriguingly, aged fibroblast-derived matrices had the opposite effect on the migration of T cells, inhibiting their motility. HAPLN1 treatment of aged fibroblasts restored motility of mononuclear immune cells, while impeding that of polymorphonuclear immune cells, which in turn affected regulatory T-cell recruitment. These data suggest that although age-related physical changes in the ECM can promote tumor cell motility, they may adversely affect the motility of some immune cells, resulting in an overall change in the immune microenvironment. Understanding the physical changes in aging skin may provide avenues for more effective therapy for older patients with melanoma. Significance: These data shed light on the mechanochemical interactions that occur between aged skin, tumor, and immune cell populations, which may affect tumor metastasis and immune cell infiltration, with implications for the efficacy of current therapies for melanoma. See related commentary by Marie and Merlino, p. 19. This article is highlighted in the In This Issue feature, p. 1
Abstract 18350: Impact of Amount vs Duration of Smoking on Incident Heart Failure and Mortality Among Community-dwelling Older Adults: Need to Reassess the Role of Pack-years as a Tool to Estimate Smoking
Authors: Amiya A Ahmed, Vera Bittner, Charity Morgan, Sijian Zhang, Gregg C Fonarow, Prakash Deedwania, Javed Butler, Wen-Chih Wu, Richard M Allman, Michel White, Ross D Fletcher, George Howard, Robert O Bonow, Wilbert S Aronow, Ali Ahmed
Journal: Circulation (2015)

Background: Clinicians and public health professionals often use pack-years (PY) to quantify amount and duration of smoking. Thus, 40 PY of smoking may mean 1 pack of cigarette a day for 40 years or 4 packs a day for 10 years. However, it is unknown if the impact of smoking as measured by PY may vary by amount and duration. Methods: Of the 3185 community-dwelling adults ≥65 years without prevalent heart failure (HF) in the Cardiovascular Health Study (CHS), 2556 were never-smokers. The 629 current smokers smoked a median of 1 (20 cigarettes) pack a day (PPD) for a median of 51 years resulting in a median of 42 PYs of smoking. Of 319 smoking ≥1 PPD, 125 smoked &lt;51 years (higher-amount-“shorter”-duration; median 49 PY) and of 336 smoking ≥51 years, 142 smoked &lt;1 PPD (lower-amount-longer-duration; median 27 PY). Age-sex-race-adjusted hazard ratios (aHR) and 95% CI for centrally-adjudicated incident HF and all-cause mortality during 13 (mean, 10) years of follow-up for the two smoker groups (vs. never smokers) were estimated in Cox regression models. Results: Patients (N=2823) had a mean (±SD) age of 74 (±6) years, 70% were women, and 16% African American. Incident HF occurred in 21%, 24% and 28% of never smokers, higher-amount-“shorter”-duration (aHR, 1.32; 95% CI, 0.91-1.91) and lower-amount-longer-duration smokers (aHR, 1.60; 95% CI, 1.14-2.16), respectively (Figure; left panel). Respective rates for all-cause mortality were 39%, 48% (aHR, 1.34; 95% CI, 1.04-1.74) and 58% (aHR, 1.73; 95% CI, 1.39-2.17; Figure; right panel). . Conclusions: Smokers who survived into older age and smoked larger amount for “shorter” duration appear to have numerically higher risk for incident HF and death than those who smoked smaller amount for longer duration, despite the fact that former group had lower pack-year estimates. These findings suggest that the use of pack-year to estimate smoking may underestimate the risk of prolonged smoking.