tbuckley/cabot-search huggingface dataset:
Abstract 14577: The Incorporation of Oxidation Resistant ApoA1-4WF in Adeno-Associated Viral and Lentiviral Gene Vectors With Robust Cholesterol Efflux in vitro
Authors: Benjamin B Pressly, Bahman Hooshdaran, Ivan S Alferiev, Philip Zoltick, Robert L Wilensky, Robert Gorman, Jonathan D Smith, Stanley L Hazen, Robert Levy, Ilia Fishbein
Journal: Circulation (2019)

Introduction: Oxidized ApoA1 present in human atherosclerotic plaque is relatively lipid-poor and interferes with reverse cholesterol transport (RCT) by reducing both ABCA1 acceptor activity in foa...
Reversible ON- and OFF-switch chimeric antigen receptors controlled by lenalidomide
Authors: Max Jan, Irene Scarfò, Rebecca C. Larson, Amanda Walker, Andrea Schmidts, Andrew A. Guirguis, Jessica A. Gasser, Mikołaj Słabicki, Amanda A. Bouffard, Ana P. Castano, Michael C. Kann, Maria L. Cabral, Alexander Tepper, Daniel E. Grinshpun, Adam S. Sperling, Taeyoon Kyung, Quinlan L. Sievers, Michael E. Birnbaum, Marcela V. Maus, Benjamin L. Ebert
Journal: Science Translational Medicine (2021)

Cell-based therapies are emerging as effective agents against cancer and other diseases. As autonomous "living drugs," these therapies lack precise control. Chimeric antigen receptor (CAR) T cells effectively target hematologic malignancies but can proliferate rapidly and cause toxicity. We developed ON and OFF switches for CAR T cells using the clinically approved drug lenalidomide, which mediates the proteasomal degradation of several target proteins by inducing interactions between the CRL4
AV Junction Ablation in Heart Failure Patients With Atrial Fibrillation Treated With Cardiac Resynchronization Therapy: The Picture Is Now Clear!⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Maurizio Gasparini, Paola Galimberti
Journal: Journal of the American College of Cardiology (2012)
Authors’ Reply to Letter to the Editor by Chen et al
Authors: Fei Gao, Nan Li, YongMei Xu, GuoWang Yang
Journal: Journal of the National Comprehensive Cancer Network (2021)

Effects ofPostoperative Radiotherapy on Survival of Patients With Stage IIIA Resected Non-Small Cell Lung Cancer: Analysis of the SEER Database."The authors found that postoperative radiotherapy (PORT) significantly improved overall survival and decreased lung cancer-related mortality in patients with stage IIIA, N2 disease with $6 positive lymph node metastases.The authors should be commended on their efforts to address an important question in thoracic oncology.However, we have some concerns.First, as shown in Tables 1 and2, the authors listed the information on postoperative chemotherapy, which was a significant parameter in patients with stage IIIA non-small cell lung cancer (NSCLC).However, the sequence of radiotherapy and surgery could be obtained in the SEER database, but the sequence and details of chemotherapy regimens was not provided. 2,3 How could the authors ensure that the chemotherapy was not given before surgery given that neoadjuvant chemotherapy might be administered to patients with suspected stage IIIA-N2 disease? CORRESPONDENCEPostoperative RT in Stage IIIA NSCLC xxxvi
Differential expression of microRNA miR-150-5p in IgA nephropathy as a potential mediator and marker of disease progression
Authors: Izabella Z.A. Pawluczyk, Athanasios Didangelos, Sean J. Barbour, Lee Er, Jan U. Becker, Roberto Martin, Scott Taylor, Jasraj S. Bhachu, Edward G. Lyons, Robert H. Jenkins, Donald Fraser, Karen Molyneux, Javier Perales-Patón, Julio Saez-Rodriguez, Jonathan Barratt
Journal: Kidney International (2021)

Understanding why certain patients with IgA nephropathy progress to kidney failure while others maintain normal kidney function remains a major unanswered question. To help answer this, we performed miRNome profiling by next generation sequencing of kidney biopsies in order to identify microRNAs specifically associated with the risk of IgA nephropathy progression. Following sequencing and validation in independent cohorts, four microRNAs (-150-5p, -155-5p, -146b-5p, -135a-5p) were found to be differentially expressed in IgA nephropathy progressors compared to non-progressors, and patients with thin membrane nephropathy, lupus nephritis and membranous nephropathy, and correlated with estimated glomerular filtration rate, proteinuria, and the Oxford MEST-C scores (five histological features that are independent predictors of clinical outcome). Each individual microRNA increased the discrimination score of the International IgAN Prediction Tool, although due to the small number of samples the results did not reach statistical significance. miR-150-5p exhibited the largest amplitude of expression between cohorts and displayed the best discrimination between IgA nephropathy progressors and non-progressors by receiver operating curve analysis (AUC: 0.8). However, expression was similarly upregulated in kidneys with established fibrosis and low estimated glomerular filtration rates at the time of biopsy. Consistent with a more generic role in kidney fibrosis, in situ hybridization revealed that miR-150-5p was found in lymphoid infiltrates, and areas of proliferation and fibrosis consistent with the known drivers of progression. Thus, miR-150-5p may be a potential functional mediator of kidney fibrosis that may add value in predicting risk of progression in IgA nephropathy and other kidney diseases.
European Association of Urology (EAU) Prognostic Factor Risk Groups for Non–muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel
Authors: Richard J. Sylvester, Oscar Rodríguez, Virginia Hernández, Diana Turturica, Lenka Bauerová, Harman Max Bruins, Johannes Bründl, Theo H. van der Kwast, Antonin Brisuda, José Rubio-Briones, Maximilian Seles, Anouk E. Hentschel, Venkata R.M. Kusuma, Nicolai Huebner, Juliette Cotte, Laura S. Mertens, Dimitrios Volanis, Olivier Cussenot, Jose D. Subiela Henríquez, Enrique de la Peña, Francesca Pisano, Michael Pešl, Antoine G. van der Heijden, Sonja Herdegen, Alexandre R. Zlotta, Jaromir Hacek, Ana Calatrava, Sebastian Mannweiler, Judith Bosschieter, David Ashabere, Andrea Haitel, Jean-François Côté, Soha El Sheikh, Luca Lunelli, Ferran Algaba, Isabel Alemany, Francesco Soria, Willemien Runneboom, Johannes Breyer, Jakko A. Nieuwenhuijzen, Carlos Llorente, Luca Molinaro, Christina A. Hulsbergen-van de Kaa, Matthias Evert, Lambertus A.L.M. Kiemeney, James N’Dow, Karin Plass, Otakar Čapoun, Viktor Soukup, Jose L. Dominguez-Escrig, Daniel Cohen, Joan Palou, Paolo Gontero, Maximilian Burger, Richard Zigeuner, Amir Hugh Mostafid, Shahrokh F. Shariat, Morgan Rouprêt, Eva M. Compérat, Marko Babjuk, Bas W.G. van Rhijn
Journal: European Urology (2021)
A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder
Authors: Adriana Feder, Sara Costi, Sarah B. Rutter, Abigail B. Collins, Usha Govindarajulu, Manish K. Jha, Sarah R. Horn, Marin Kautz, Morgan Corniquel, Katherine A. Collins, Laura Bevilacqua, Andrew M. Glasgow, Jess Brallier, Robert H. Pietrzak, James W. Murrough, Dennis S. Charney
Journal: American Journal of Psychiatry (2021)

Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors' previous proof-of-concept randomized controlled trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first randomized controlled trial to test the efficacy and safety of repeated intravenous ketamine infusions for the treatment of chronic PTSD.Individuals with chronic PTSD (N=30) were randomly assigned (1:1) to receive six infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) (psychoactive placebo control) over 2 consecutive weeks. Clinician-rated and self-report assessments were administered 24 hours after the first infusion and at weekly visits. The primary outcome measure was change in PTSD symptom severity, as assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), from baseline to 2 weeks (after completion of all infusions). Secondary outcome measures included the Impact of Event Scale-Revised, the Montgomery-Åsberg Depression Rating Scale (MADRS), and side effect measures.The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2. At week 2, the mean CAPS-5 total score was 11.88 points (SE=3.96) lower in the ketamine group than in the midazolam group (d=1.13, 95% CI=0.36, 1.91). Sixty-seven percent of participants in the ketamine group were treatment responders, compared with 20% in the midazolam group. Among ketamine responders, the median time to loss of response was 27.5 days following the 2-week course of infusions. Ketamine infusions were well tolerated overall, without serious adverse events.This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD. Further studies are warranted to understand ketamine's full potential as a treatment for chronic PTSD.
Hierarchical models of psychopathology: empirical support, implications, and remaining issues
Authors: Benjamin B. Lahey, Tyler M. Moore, Antonia N. Kaczkurkin, David H. Zald
Journal: World Psychiatry (2021)

There is an ongoing revolution in psychology and psychiatry that will likely change how we conceptualize, study and treat psychological problems.­ Many theorists now support viewing psychopathology as consisting of continuous dimensions rather than discrete diagnostic categories. Indeed, recent papers have proposed comprehensive taxonomies of psychopathology dimensions to replace the DSM and ICD taxonomies of categories. The proposed dimensional taxonomies, which portray psychopathology as hierarchically organized correlated dimensions, are now well supported at phenotypic levels. Multiple studies show that both a general factor of psychopathology at the top of the hierarchy and specific factors at lower levels predict different functional outcomes. Our analyses of data on a large representative sample of child and adolescent twins suggested the causal hypothesis that phenotypic correlations among dimensions of psychopathology are the result of many familial influences being pleiotropic. That is, most genetic variants and shared environmental factors are hypothesized to non‐specifically influence risk for multiple rather than individual dimensions of psychopathology. In contrast, person‐specific experiences tend to be related to individual dimensions. This hierarchical causal hypothesis has been supported by both large‐scale family and molecular genetic studies. Current research focuses on three issues. First, the field has not settled on a preferred statistical model for studying the hierarchy of causes and phenotypes. Second, in spite of encouraging progress, the neurobiological correlates of the hierarchy of dimensions of psychopathology are only partially described. Third, although there are potentially important clinical implications of the hierarchical model, insufficient research has been conducted to date to rec­ommend evidence‐based clinical practices.
Non-Hodgkin's Lymphomas
Authors: Andrew D. Zelenetz, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, John C. Byrd, Myron S. Czuczman, Luis Fayad, Andres Forero, Martha J. Glenn, Jon P. Gockerman, Leo I. Gordon, Nancy Lee Harris, Richard T. Hoppe, Steven M. Horwitz, Mark S. Kaminski, Youn H. Kim, Ann S. Lacasce, Tariq I. Mughal, Auyporn Nademanee, Pierluigi Porcu, Oliver Press, Leonard Prosnitz, Nashitha Reddy, Mitchell R. Smith, Lubomir Sokol, Lode Swinnen, Julie Marie Vose, William G. Wierda, Joachim Yahalom, Furhan Yunus
Journal: Journal of the National Comprehensive Cancer Network (2011)
Early-life EV-A71 infection augments allergen-induced airway inflammation in asthma through trained macrophage immunity
Authors: Pei-Chi Chen, Yu-Ting Shao, Miao-Hsi Hsieh, Hui-Fang Kao, Wen-Shuo Kuo, Shih-Min Wang, Shun-Hua Chen, Lawrence Shih Hsin Wu, Hui-Ju Tsai, Jiu-Yao Wang
Journal: Cellular and Molecular Immunology (2021)
Preclinical Characterization of MAU868, a Novel Neutralizing Antibody Targeting BK Virus
Authors: Atul Sathe, Mark Knapp, Lihong Zhao, Peter Kim, Andreas Hein, Meike Scharenberg, Jacob Shaul, Kelly A. Wong, Steven J. Kovacs, Elisabetta Traggiai, Amy Patick, Johanna R. Abend
Journal: Journal of the American Society of Nephrology (2020)
Abstract 15199: Effects of Ageing on Nitric Oxide Signalling in Women: Comparison with Polycystic Ovarian Syndrome
Authors: Wai Ping Chan, Doan T Ngo, Aaron Sverdlov, Yuliy Y Chirkov, John D Horowitz
Journal: Circulation (2012)

Ageing per se represents an independent risk factor for ischemic heart disease, but the mechanism(s) underlying this effect remains controversial. Polycystic ovarian syndrome (PCOS) appears to enge...
Identification of neuroblastoma cell lines with uncommon TAZ<sup>+</sup>/mesenchymal stromal cell phenotype with strong suppressive activity on natural killer cells
Authors: Claudia Canzonetta, Andrea Pelosi, Sabina Di Matteo, Irene Veneziani, Nicola Tumino, Paola Vacca, Enrico Munari, Marco Pezzullo, Charles Theuer, Rita De Vito, Vito Pistoia, Luigi Tomao, Franco Locatelli, Lorenzo Moretta, Ignazio Caruana, Bruno Azzarone
Journal: Journal for ImmunoTherapy of Cancer (2021)

Neuroblastoma (NB) is the most common, extracranial childhood solid tumor arising from neural crest progenitor cells and is a primary cause of death in pediatric patients. In solid tumors, stromal elements recruited or generated by the cancer cells favor the development of an immune-suppressive microenvironment. Herein, we investigated in NB cell lines and in NB biopsies, the presence of cancer cells with mesenchymal phenotype and determined the immune-suppressive properties of these tumor cells on natural killer (NK) cells. We assessed the mesenchymal stromal cell (MSC)-like phenotype and function of five human NB cell lines and the presence of this particular subset of neuroblasts in NB biopsies using flow-cytometry, immunohistochemistry, RT-qPCR, cytotoxicity assays, western blot and silencing strategy. We corroborated our data consulting a public gene-expression dataset. Two NB cell lines, SK-N-AS and SK-N-BE(2)C, exhibited an unprecedented MSC phenotype (CD105+/CD90+/CD73+/CD29+/CD146+/GD2+/TAZ+). In these NB-MSCs, the ectoenzyme CD73 and the oncogenic/immune-regulatory transcriptional coactivator TAZ were peculiar markers. Their MSC-like nature was confirmed by their adipogenic and osteogenic differentiation potential. Immunohistochemical analysis confirmed the presence of neuroblasts with MSC phenotype (CD105+/CD73+/TAZ+). Moreover, a public gene-expression dataset revealed that, in stage IV NB, a higher expression of TAZ and CD105 strongly correlated with a poorer outcome.Among the NB-cell lines analyzed, only NB-MSCs exhibited multifactorial resistance to NK-mediated lysis, inhibition of activating NK receptors, signal adaptors and of NK-cell cytotoxicity through cell-cell contact mediated mechanisms. The latter property was controlled partially by TAZ, since its silencing in NB cells efficiently rescued NK-cell cytotoxic activity, while its overexpression induced opposite effects in non-NB-MSC cells. We identified a novel NB immunoregulatory subset that: (i) displayed phenotypic and functional properties of MSC, (ii) mediated multifactorial resistance to NK-cell-induced killing and (iii) efficiently inhibited, in coculture, the cytotoxic activity of NK cells against target cells through a TAZ-dependent mechanism. These findings indicate that targeting novel cellular and molecular components may disrupt the immunomodulatory milieu of the NB microenvironment ameliorating the response to conventional treatments as well as to advanced immunotherapeutic approaches, including adoptive transfer of NK cells and chimeric antigen receptor T or NK cells.
Lenalidomide versus bortezomib maintenance after frontline autologous stem cell transplantation for multiple myeloma
Authors: Marc-Andrea Baertsch, Elias K. Mai, Thomas Hielscher, Uta Bertsch, Hans J. Salwender, Markus Munder, Stephan Fuhrmann, Ulrich Dührsen, Peter Brossart, Kai Neben, Jana Schlenzka, Christina Kunz, Marc S. Raab, Jens Hillengaß, Anna Jauch, Anja Seckinger, Dirk Hose, Steffen Luntz, Pieter Sonneveld, Henk Lokhorst, Hans Martin, Martin Goerner, Martin Hoffmann, Hans-Walter Lindemann, Helga Bernhard, Igor W. Blau, Christof Scheid, Britta Besemer, Katja C. Weisel, Mathias Hänel, Jan Dürig, Hartmut Goldschmidt
Journal: Blood Cancer Journal (2021)

Abstract Lenalidomide (LEN) maintenance (MT) post autologous stem cell transplantation (ASCT) is standard of care in newly diagnosed multiple myeloma (MM) but has not been compared to other agents in clinical trials. We retrospectively compared bortezomib (BTZ; n = 138) or LEN ( n = 183) MT from two subsequent GMMG phase III trials. All patients received three cycles of BTZ-based triplet induction and post-ASCT MT. BTZ MT (1.3 mg/m 2 i.v.) was administered every 2 weeks for 2 years. LEN MT included two consolidation cycles (25 mg p.o., days 1–21 of 28 day cycles) followed by 10–15 mg/day for 2 years. The BTZ cohort more frequently received tandem ASCT (91% vs. 33%) due to different tandem ASCT strategies. In the LEN and BTZ cohort, 43% and 46% of patients completed 2 years of MT as intended ( p = 0.57). Progression-free survival (PFS; HR = 0.83, p = 0.18) and overall survival (OS; HR = 0.70, p = 0.15) did not differ significantly with LEN vs. BTZ MT. Patients with &lt;nCR after first ASCT were assigned tandem ASCT in both trials. In patients with &lt;nCR and tandem ASCT (LEN: n = 54 vs. BTZ: n = 84), LEN MT significantly improved PFS (HR = 0.61, p = 0.04) but not OS (HR = 0.46, p = 0.09). In conclusion, the significant PFS benefit after eliminating the impact of different tandem ASCT rates supports the current standard of LEN MT after ASCT.
Engineering exosomes for targeted drug delivery
Authors: Yujie Liang, Li Duan, Jianping Lu, Jiang Xia
Journal: Theranostics (2021)

Exosomes are cell-derived nanovesicles that are involved in the intercellular transportation of materials. Therapeutics, such as small molecules or nucleic acid drugs, can be incorporated into exosomes and then delivered to specific types of cells or tissues to realize targeted drug delivery. Targeted delivery increases the local concentration of therapeutics and minimizes side effects. Here, we present a detailed review of exosomes engineering through genetic and chemical methods for targeted drug delivery. Although still in its infancy, exosome-mediated drug delivery boasts low toxicity, low immunogenicity, and high engineerability, and holds promise for cell-free therapies for a wide range of diseases.
Spatiotemporal Evolution of the Global Species Diversity of <i>Rhododendron</i>
Authors: Xiao-Mei Xia, Miao-Qin Yang, Cong-Li Li, Si-Xin Huang, Wei-Tao Jin, Ting-Ting Shen, Fei Wang, Xiao-Hua Li, Watanabe Yoichi, Le-Hua Zhang, Yuan-Run Zheng, Xiao-Quan Wang
Journal: Molecular Biology and Evolution (2021)

Abstract Evolutionary radiation is a widely recognized mode of species diversification, but its underlying mechanisms have not been unambiguously resolved for species-rich cosmopolitan plant genera. In particular, it remains largely unknown how biological and environmental factors have jointly driven its occurrence in specific regions. Here, we use Rhododendron, the largest genus of woody plants in the Northern Hemisphere, to investigate how geographic and climatic factors, as well as functional traits, worked together to trigger plant evolutionary radiations and shape the global patterns of species richness based on a solid species phylogeny. Using 3,437 orthologous nuclear genes, we reconstructed the first highly supported and dated backbone phylogeny of Rhododendron comprising 200 species that represent all subgenera, sections, and nearly all multispecies subsections, and found that most extant species originated by evolutionary radiations when the genus migrated southward from circumboreal areas to tropical/subtropical mountains, showing rapid increases of both net diversification rate and evolutionary rate of environmental factors in the Miocene. We also found that the geographically uneven diversification of Rhododendron led to a much higher diversity in Asia than in other continents, which was mainly driven by two environmental variables, that is, elevation range and annual precipitation, and were further strengthened by the adaptation of leaf functional traits. Our study provides a good example of integrating phylogenomic and ecological analyses in deciphering the mechanisms of plant evolutionary radiations, and sheds new light on how the intensification of the Asian monsoon has driven evolutionary radiations in large plant genera of the Himalaya-Hengduan Mountains.
Recurrent XPO1 mutations alter pathogenesis of chronic lymphocytic leukemia
Authors: Janek S. Walker, Zachary A. Hing, Bonnie Harrington, Jordan Baumhardt, Hatice Gulcin Ozer, Amy Lehman, Brian Giacopelli, Larry Beaver, Katie Williams, Jordan N. Skinner, Casey B. Cempre, Qingxiang Sun, Sharon Shacham, Benjamin R. Stromberg, Matthew K. Summers, Lynne V. Abruzzo, Laura Rassenti, Thomas J. Kipps, Sameer Parikh, Neil E. Kay, Kerry A. Rogers, Jennifer A. Woyach, Vincenzo Coppola, Yuh Min Chook, Christopher Oakes, John C. Byrd, Rosa Lapalombella
Journal: Journal of Hematology & Oncology (2021)

Abstract Background Exportin 1 (XPO1/CRM1) is a key mediator of nuclear export with relevance to multiple cancers, including chronic lymphocytic leukemia (CLL). Whole exome sequencing has identified hot-spot somatic XPO1 point mutations which we found to disrupt highly conserved biophysical interactions in the NES-binding groove, conferring novel cargo-binding abilities and forcing cellular mis-localization of critical regulators. However, the pathogenic role played by change-in-function XPO1 mutations in CLL is not fully understood. Methods We performed a large, multi-center retrospective analysis of CLL cases ( N = 1286) to correlate nonsynonymous mutations in XPO1 (predominantly E571K or E571G; n = 72) with genetic and epigenetic features contributing to the overall outcomes in these patients. We then established a mouse model with over-expression of wildtype (wt) or mutant (E571K or E571G) XPO1 restricted to the B cell compartment (Eµ-XPO1). Eµ-XPO1 mice were then crossed with the Eµ-TCL1 CLL mouse model. Lastly, we determined crystal structures of XPO1 (wt or E571K) bound to several selective inhibitors of nuclear export (SINE) molecules (KPT-185, KPT-330/Selinexor, and KPT-8602/Eltanexor). Results We report that nonsynonymous mutations in XPO1 associate with high risk genetic and epigenetic features and accelerated CLL progression. Using the newly-generated Eµ-XPO1 mouse model, we found that constitutive B-cell over-expression of wt or mutant XPO1 could affect development of a CLL-like disease in aged mice. Furthermore, concurrent B-cell expression of XPO1 with E571K or E571G mutations and TCL1 accelerated the rate of leukemogenesis relative to that of Eµ-TCL1 mice. Lastly, crystal structures of E571 or E571K-XPO1 bound to SINEs, including Selinexor, are highly similar, suggesting that the activity of this class of compounds will not be affected by XPO1 mutations at E571 in patients with CLL. Conclusions These findings indicate that mutations in XPO1 at E571 can drive leukemogenesis by priming the pre-neoplastic lymphocytes for acquisition of additional genetic and epigenetic abnormalities that collectively result in neoplastic transformation.