tbuckley/cabot-search huggingface dataset:
Host response to immune checkpoint inhibitors contributes to tumor aggressiveness
Authors: Irina Khononov, Eyal Jacob, Ella Fremder, Nili Dahan, Michal Harel, Ziv Raviv, Boris Krastev, Yuval Shaked
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immune checkpoint inhibitors (ICIs) have made a paradigm shift in clinical oncology due to unprecedented long-term remissions. However, only a small proportion of patients respond to ICI therapy. It is, therefore, essential to understand the mechanisms driving therapy resistance and to develop strategies for increasing response rates. We previously demonstrated that in response to various cancer treatment modalities, the host activates a range of biological processes that promote tumor regrowth and metastasis. Here, we characterize the host-mediated response to ICI therapy, and investigate its contribution to therapy resistance. Tumor cell migration, invasion and motility were assessed in the presence of plasma from ICI-treated mice and patients. Immune cell composition in peripheral blood and tumors of ICI-treated mice was assessed by flow and mass cytometry. Plasma host factors driving tumor aggressiveness were identified by proteomic profiling, followed by bioinformatic analysis. The therapeutic effect of inhibiting host-mediated processes in ICI-treated mice was assessed in a tumor model. Tumor cells exhibit enhanced migratory and invasive properties in vitro on exposure to plasma from anti-PD1-treated mice. Moreover, mice intravenously injected with plasma-exposed tumor cells display increased metastatic burden and mortality rate in comparison to control arms. Furthermore, tumors from anti-PD1-treated mice as well as Matrigel plugs containing plasma from anti-PD1-treated mice are highly infiltrated with immune cell types associated with both antitumor and protumor activity. These collective findings suggest that anti-PD1 treatment induces a systemic host response that potentially counteracts the drug's therapeutic activity. Proteomic profiling of plasma from anti-PD1-treated mice reveals an activation of multiple biological pathways associated with tumor aggressiveness. Consequently, blocking IL-6, one of the key drivers of the identified biological pathways, counteracts ICI-induced metastatic properties in vitro and improves ICI treatment efficacy in vivo. Lastly, plasma samples from ICI-treated non-small cell lung cancer patients differentially affect tumor cell aggressiveness in vitro, with enhanced tumor cell motility correlating with a worse clinical outcome. ICI therapy induces host-mediated processes that contribute to therapy resistance. Identification and analysis of such processes may lead to the discovery of biomarkers for clinical response and strategies for overcoming therapy resistance.
A shared COVID-19 testimony
Authors: Rageshri Dhairyawan
Journal: The Lancet (2021)

"Six feet away, a father, a man I am yet to lay eyes on, is dying of a disease only named a month ago." This unfamiliar clinical territory starts Rachel Clarke's Breathtaking: Inside the NHS in a Time of Pandemic as she describes reviewing Winston, a patient admitted with COVID-19. She relates the effort to communicate care to Winston and his sons while wearing personal protective equipment (PPE) and the anxiety of trying to do her job in a situation unimaginable only a few months before.
Avapritinib reduced cutaneous symptoms and mast cell (MC) burden in patients (pts) with indolent systemic mastocytosis (ISM) in the PIONEER study
Authors: K. Hartmann, S. Broesby-Olsen, F. Siebenhaar, H. O. Elberink, J. Gotlib, V Sabato, M. Castells, M. W. Deininger, M. L. Heaney, D. H. Radia, M. Triggiani, P. Van Daele, D. J. Deangelo, O. Schmidt-Kittler, H. Lin, A. Morrison, B. Mar, C. Akin, M. Maurer
Journal: Allergy (2020)
Phase II/III clinical results of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (CIS) patients.
Authors: Karim Chamie, Sam Chang, Mark L. Gonzalgo, Eugene V. Kramolowsky, Wade J. Sexton, Sandeep K. Reddy, Paul Bhar, Chad Garner, Patrick Soon-Shiong
Journal: Journal of Clinical Oncology (2021)

510 Background: Patients with NMIBC CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is a mutant IL-15-based immunostimulatory fusion protein complex (IL-15RαFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Phase Ib data in BCG-naive patients with NMIBC demonstrate that intravesical administration of N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. An open-label, 3 cohort multicenter phase II/III study (QUILT 3.032) of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened. We report here the interim analysis of Cohort A, BCG-unresponsive (CIS) [with or without Ta or T1 disease], as of December 2020 data cutoff. Methods: All treated patients received intravesical N-803 plus BCG, consistent with the standard induction/maintenance treatment schedule. The primary endpoint for Cohort A of this phase II/III study is incidence of complete response (CR) of CIS at any time. Results: To date, 80 patients have enrolled in cohort A of this phase II/III trial. Evaluable analysis at this time shows CR rate at any time of 72% (N=51/71); for patients achieving CR, the probability of maintaining a CR for 12 months is 59%, with a median duration of complete response of 19.2 (7.6, 26.4) months. Low-grade treatment related AEs include dysuria, hematuria, and pollakiurua (all 16%), urgency (14%), and bladder spasm (8%), all other AEs were seen at 6% or less. A total of 9 subjects experienced at least 1 treatment emergent SAE (Severe Adverse event), the SAE rate is 1% for any given AE. No treatment emergent SAE’s were considered treatment related. No immune related SAE’s have been seen. To date, 10/80 (12.5%) patients proceeded to cystectomy in this BCG unresponsive population. Conclusions:With a CR rate of 72%, N-803 has met its primary endpoint with 59% probability of CR patients maintaining CR for at least 12 months. With the observed strong efficacy and an SAE rate of 1%, N-803 represents a novel treatment option for BCG unresponsive CIS with a favorable benefit:risk ratio, in a therapeutically challenging disease. Clinical trial information: NCT03022825.
Abstract 2077: Shortening Time to Cardiac Catheterization Is Associated with Improved Outcomes Among Patients with Non-ST-segment Elevation Acute Coronary Syndromes: Results from the Randomized SYNERGY Trial
Authors: Pierluigi Tricoci, Yuliya Lokhnygina, Lisa G Berdan, Steven R Steinhubl, Dietrich C Gulba, Harvey D White, Neil S Kleiman, Anatoly Langer, Robert M Califf, James J Ferguson, Elliott M Antman, L K Newby, Robert A Harrington, Kenneth W Mahaffey
Journal: Circulation (2006)

Background: Optimal timing of cardiac catheterization remains unclear. We evaluated the relation between time from hospital admission to cath (TTC) and outcomes among NSTE ACS patients who received...
Letter by Carrizales-Sepúlveda et al Regarding Article, “Spectrum of Cardiac Manifestations in COVID-19: A Systematic Echocardiographic Study”
Authors: Edgar Francisco Carrizales-Sepúlveda, Raymundo Vera-Pineda, Ramiro Flores-Ramírez
Journal: Circulation (2021)

We read with great interest the recent publication by Szekely et al in which they prospectively studied 100 patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using echocardiography. 1 They found that among patients with coronavirus disease 2019 (COVID-19), the most common echocardiographic manifestation is right ventricular dilation in 39% of the patients, followed by left ventricular (LV) diastolic dysfunction in 16%, and LV systolic dysfunction in 10%. 1 In their cohort, 32% of the patients had a normal echocardiographic evaluation.Among their conclusions, the authors state that LV systolic dysfunction is uncommon in COVID-19. 1 To define LV systolic dysfunction, the authors used LV ejection fraction (LVEF), which is known to have potential limitations. 2First, LVEF is only affected late in disease progression, so its sensitivity to detect subtle myocardial damage is low.Second, the authors point out that their subjects had a reduced LV chamber size compared with normal standard values. 1It is known that LVEF is dependent on volume and pressure conditions and right ventricular dilation that compromises LV size could affect LVEF determination. 2 It is well known that the assessment of LV function using global longitudinal strain (GLS) measured by speckle tracking allows the detection of subtle, subclinical systolic dysfunction in several types of patients.Left ventricular GLS has been found to be affected in critically ill patients irrespective of LVEF and has been related to a worse prognosis. 3Recently, right ventricular longitudinal strain was used to detect early dysfunction in patients with COVID-19 and found to be a powerful predictor of mortality. 4Unfortunately, LV GLS has only been described in a few patients with COVID-19. 5Therefore, we raise the following questions: Could LV GLS have been impaired in this population (those with a normal echocardiogram or with right ventricular dilation or diastolic dysfunction), and could this have an effect on prognosis?Although acquisition of images for GLS can be challenging in this subset of patients, it could definitely provide valuable information for the evaluation of subjects with COVID-19.Meanwhile, we commend the authors for this read and for the valuable information offered in this time of need.
Abstract 13417: HFmEF Differs From HFpEF and HFrEF in Advanced CMR Imaging Markers of Adverse Cardiac Remodeling
Authors: Patrick J Doeblin, Burkert Pieske, Sebastian Kelle, Rolf Gebker, Thomas Lapinskas, Frank Edelmann, Djawid Hashemi, Hans-Dirk Duengen
Journal: Circulation (2018)

Introduction: Heart failure is a clinical diagnosis that is further divided based on left ventricular ejection fraction. Recent guidelines suggest the following classification: Heart failure with r...
Considering Sex as a Biological Variable in Basic and Clinical Studies: An Endocrine Society Scientific Statement
Authors: Aditi Bhargava, Arthur P Arnold, Debra A Bangasser, Kate M Denton, Arpana Gupta, Lucinda M Hilliard Krause, Emeran A Mayer, Margaret McCarthy, Walter L Miller, Armin Raznahan, Ragini Verma
Journal: Endocrine Reviews (2021)

In May 2014, the National Institutes of Health (NIH) stated its intent to "require applicants to consider sex as a biological variable (SABV) in the design and analysis of NIH-funded research involving animals and cells." Since then, proposed research plans that include animals routinely state that both sexes/genders will be used; however, in many instances, researchers and reviewers are at a loss about the issue of sex differences. Moreover, the terms sex and gender are used interchangeably by many researchers, further complicating the issue. In addition, the sex or gender of the researcher might influence study outcomes, especially those concerning behavioral studies, in both animals and humans. The act of observation may change the outcome (the "observer effect") and any experimental manipulation, no matter how well-controlled, is subject to it. This is nowhere more applicable than in physiology and behavior. The sex of established cultured cell lines is another issue, in addition to aneuploidy; chromosomal numbers can change as cells are passaged. Additionally, culture medium contains steroids, growth hormone, and insulin that might influence expression of various genes. These issues often are not taken into account, determined, or even considered. Issues pertaining to the "sex" of cultured cells are beyond the scope of this Statement. However, we will discuss the factors that influence sex and gender in both basic research (that using animal models) and clinical research (that involving human subjects), as well as in some areas of science where sex differences are routinely studied. Sex differences in baseline physiology and associated mechanisms form the foundation for understanding sex differences in diseases pathology, treatments, and outcomes. The purpose of this Statement is to highlight lessons learned, caveats, and what to consider when evaluating data pertaining to sex differences, using 3 areas of research as examples; it is not intended to serve as a guideline for research design.
Combination Therapies for Precision Oncology: The Ultimate Whack-A-Mole Game
Authors: Roman Groisberg, Vivek Subbiah
Journal: Clinical Cancer Research (2021)

Abstract The single-agent activity of MEK inhibitors in MAPK or CDK4/6 inhibitors in cyclin pathway aberrant tumors has been limited. The combination of trametinib and palbociclib demonstrates safety, tolerability, and clinical activity in a histology-independent manner, representing a therapeutic approach for patients harboring co-occurring aberrations. See related article by Kato et al., p. 2792
Factors associated with coinfections in invasive aspergillosis: a retrospective cohort study
Authors: François Danion, Céline Duval, François Séverac, Philippe Bachellier, Ermanno Candolfi, Vincent Castelain, Raphaël Clere-Jehl, Julie Denis, Laurence Dillenseger, Eric Epailly, Justine Gantzer, Blandine Guffroy, Yves Hansmann, Jean-Etienne Herbrecht, Valérie Letscher-Bru, Pierre Leyendecker, Pauline Le Van Quyen, Pierre-Olivier Ludes, Guillaume Morel, Bruno Moulin, Catherine Paillard, Benjamin Renaud-Picard, Anne-Claude Roche, Marcela Sabou, Francis Schneider, Morgane Solis, Emilie Talagrand-Reboul, Francis Veillon, Marie-Pierre Ledoux, Célestine Simand, Raoul Herbrecht, Pietro Francesco Addeo, Dominique Astruc, Mathieu Baldacini, Karin Bilger, Marie-Pierrette Chenard, Olivier Collange, Tristan Degot, Nadia Dhif, Elise Dicop, Samira Fafi-Kremer, Luc-Matthieu Fornecker, Charline Fuseau, Max Guillot, Mary-Line Harlay, Ralf Janssen-Langenstein, Benoît Jaulhac, Charlotte Kaeuffer, Romain Kessler, Christine Kummerlen, Annegret Laplace, Anne Launoy, Bruno Lioure, Hamid Merdji, Paul-Michel Mertes, Shanti Natarajan-Ame, Gabriel Nisand, Michele Porzio, Julien Pottecher, Anne-Claude Roche, Maleka Schenck-Dhif, Cécile Sonntag, Elise Toussaint, Anne Zilliox
Journal: Clinical Microbiology and Infection (2021)
All-polymeric transient neural probe for prolonged in-vivo electrophysiological recordings
Authors: Laura Ferlauto, Paola Vagni, Adele Fanelli, Elodie Geneviève Zollinger, Katia Monsorno, Rosa Chiara Paolicelli, Diego Ghezzi
Journal: Biomaterials (2021)

Transient bioelectronics has grown fast, opening possibilities never thought before. In medicine, transient implantable devices are interesting because they could eliminate the risks related to surgical retrieval and reduce the chronic foreign body reaction. Despite recent progress in this area, the potential of transient bioelectronics is still limited by their short functional lifetime owed to the fast dissolution rate of degradable metals, which is typically a few days or weeks. Here we report that a switch from degradable metals to an entirely polymer-based approach allows for a slower degradation process and a longer lifetime of the transient probe, thus opening new possibilities for transient medical devices. As a proof-of-concept, we fabricated all-polymeric transient neural probes that can monitor brain activity in mice for a few months, rather than a few days or weeks. Also, we extensively evaluated the foreign body reaction around the implant during the probe degradation. This kind of devices might pave the way for several applications in neuroprosthetics.
Abstract 14193: Genetic Polymorphisms Associated with Coronary Artery Disease in Patients with Previous Low Cardiovascular Risk, Assessed by Traditional Risk Factors
Authors: Isabel M Mendonca, Susana Gomes, Bruno Silva, Andreia Pereira, Ana Celia Sousa, Sonia Freitas, Ana Isabel Freitas, Roberto Palma dos Reis
Journal: Circulation (2012)

Several studies have attempted to link genetic polymorphisms with coronary artery disease (CAD) onset. The risk of each polymorphism is lower (OR=1.1 or 1.2) than that associated with traditional r...
Abstract PO-029: Survival prediction of non-small cell lung cancer by deep learning model integrating clinical and positron emission tomography data
Authors: Sae-Ryung Kang, Seungwon Oh, In-Jae Oh, Jung-Joon Min, Hee-Seung Bom, Hyung-Jeong Yang, Guee-Sang Lee, Soo-Hyung Kim, Min Soo Kim
Journal: Clinical Cancer Research (2021)

Abstract The Cox proportional hazards model (CPH), the standard method for survival analysis in cancer patients, is difficult to use maximal information of positron emission tomography (PET) images containing information that reflects underlying pathophysiology. In this retrospective study, we aimed to investigate a deep learning model integrating clinical and PET image data to improve survival prediction in non-small cell lung cancer (NSCLC) patients. We developed a bimodal learning model thorough DeepSurv-based model using 3D-CNN-based 3D-Resnet model for image data and deep neural network (DNN) model for clinical data. DeepSurv-based model combining clinical and PET image data showed the best performance among the four models, the c-index of the training and testing sets reaching 0.898 and 0.768, respectively, followed by DeepSurv-based model for single modalities (clinical (0.763/0.740) or PET (0.773/0.743)) and CPH (0.726/0.736). Deep learning-based survival prediction with combination of two modalities may improve prediction accuracy in NSCLC patients. Citation Format: Sae-Ryung Kang, Seungwon Oh, In-Jae Oh, Jung-Joon Min, Hee-Seung Bom, Hyung-Jeong Yang, Guee-Sang Lee, Soo-Hyung Kim, Min Soo Kim. Survival prediction of non-small cell lung cancer by deep learning model integrating clinical and positron emission tomography data [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-029.
Heterospheroid formation improves therapeutic efficacy of mesenchymal stem cells in murine colitis through immunomodulation and epithelial regeneration
Authors: Shobha Regmi, Yoojin Seo, Ji-Su Ahn, Shiva Pathak, Suman Acharya, Tiep Tien Nguyen, Simmyung Yook, Jong-Hyuk Sung, Jun-Beom Park, Jong Oh Kim, Chul Soon Young, Hyung-Sik Kim, Jee-Heon Jeong
Journal: Biomaterials (2021)
Five-year outcome of respiratory muscle weakness at intensive care unit discharge: secondary analysis of a prospective cohort study
Authors: Nathalie Van Aerde, Philippe Meersseman, Yves Debaveye, Alexander Wilmer, Jan Gunst, Michael P Casaer, Joost Wauters, Pieter J Wouters, Rik Gosselink, Greet Van den Berghe, Greet Hermans
Journal: Thorax (2021)

Purpose To assess the association between respiratory muscle weakness (RMW) at intensive care unit (ICU) discharge and 5-year mortality and morbidity, independent from confounders including peripheral muscle strength. Methods Secondary analysis of the prospective 5-year follow-up of the EPaNIC cohort (ClinicalTrials.gov: NCT00512122 ), limited to 366 patients screened for respiratory and peripheral muscle strength in the ICU with maximal inspiratory pressure (MIP) after removal of the artificial airway, and the Medical Research Council sum score. RMW was defined as an absolute value of MIP &lt;30 cmH 2 O. Associations between RMW at (or closest to) ICU discharge and all-cause 5-year mortality, and key measures of 5-year physical function, comprising respiratory muscle strength (MIP), hand-grip strength (HGF), 6 min walk distance (6MWD) and physical function of the SF-36 quality-of-life questionnaire (PF-SF-36), were assessed with Cox proportional hazards and linear regression models, adjusted for confounders including peripheral muscle strength. Results RMW was present in 136/366 (37.2%) patients at ICU discharge. RMW was not independently associated with 5-year mortality (HR with 95% CI 1.273 (0.751 to 1.943), p=0.352). Among 156five-year survivors, those with, as compared with those without RMW demonstrated worse physical function (MIP (absolute value, cmH 2 O): 62(42–77) vs 94(78–109), p&lt;0.001; HGF (%pred): 67(44–87) vs 96(68–110), p&lt;0.001; 6MWD (%pred): 87(74–102) vs 99 (80–111), p=0.009; PF-SF-36 (score): 55 (30–80) vs 80 (55–95), p&lt;0.001). Associations between RMW and morbidity endpoints remained significant after adjustment for confounders (effect size with 95% CI: MIP: −23.858 (−32.097 to −15.027), p=0.001; HGF: −18.591 (−30.941 to −5.744), p=0.001; 6MWD (transformed): −1587.007 (−3073.763 to −179.253), p=0.034; PF-SF-36 (transformed): 1.176 (0.144–2.270), p=0.036). Conclusions RMW at ICU discharge is independently associated with 5-year morbidity but not 5-year mortality.
Links between gut microbiome composition and fatty liver disease in a large population sample
Authors: Matti O. Ruuskanen, Fredrik Åberg, Ville Männistö, Aki S. Havulinna, Guillaume Méric, Yang Liu, Rohit Loomba, Yoshiki Vázquez-Baeza, Anupriya Tripathi, Liisa M. Valsta, Michael Inouye, Pekka Jousilahti, Veikko Salomaa, Mohit Jain, Rob Knight, Leo Lahti, Teemu J. Niiranen
Journal: Gut Microbes (2021)

Fatty liver disease is the most common liver disease in the world. Its connection with the gut microbiome has been known for at least 80 y, but this association remains mostly unstudied in the general population because of underdiagnosis and small sample sizes. To address this knowledge gap, we studied the link between the Fatty Liver Index (FLI), a well-established proxy for fatty liver disease, and gut microbiome composition in a representative, ethnically homogeneous population sample of 6,269 Finnish participants. We based our models on biometric covariates and gut microbiome compositions from shallow metagenome sequencing. Our classification models could discriminate between individuals with a high FLI (≥60, indicates likely liver steatosis) and low FLI (<60) in internal cross-region validation, consisting of 30% of the data not used in model training, with an average AUC of 0.75 and AUPRC of 0.56 (baseline at 0.30). In addition to age and sex, our models included differences in 11 microbial groups from class Clostridia, mostly belonging to orders Lachnospirales and Oscillospirales. Our models were also predictive of the high FLI group in a different Finnish cohort, consisting of 258 participants, with an average AUC of 0.77 and AUPRC of 0.51 (baseline at 0.21). Pathway analysis of representative genomes of the positively FLI-associated taxa in (NCBI) Clostridium subclusters IV and XIVa indicated the presence of, e.g., ethanol fermentation pathways. These results support several findings from smaller case–control studies, such as the role of endogenous ethanol producers in the development of the fatty liver.
Locating COVID-19 Monoclonal Antibody Therapies: The Journal of the American Medical Association
Authors: Rita M. A. Rubin
Journal: JAMA (2021)

Physicians and patients in search of outpatient monoclonal antibody therapies for coronavirus disease 2019 (COVID-19) can turn to a US government website and enter their zip code  In November 2020, the Food and Drug Administration authorized emergency use of the monoclonal antibodies for treating patients with mild or moderate COVID-19 who are at high risk of developing more severe disease that requires hospitalization  Clinical trial data as well as anecdotal information from communities suggest that the monoclonal antibodies might prevent the worsening of symptoms and keep patients out of the hospital  The US Department of Health and Human Services has signed agreements with Regeneron to buy about 300,000 courses of its casirivimab and imdevimab combination treatment and with Eli Lilly and Company to buy about 3 million courses of its bamlanivimab therapy if needed