tbuckley/cabot-search huggingface dataset:
Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19
Authors: Joana P. Bernardes, Neha Mishra, Florian Tran, Thomas Bahmer, Lena Best, Johanna I. Blase, Dora Bordoni, Jeanette Franzenburg, Ulf Geisen, Jonathan Josephs-Spaulding, Philipp Köhler, Axel Künstner, Elisa Rosati, Anna C. Aschenbrenner, Petra Bacher, Nathan Baran, Teide Boysen, Burkhard Brandt, Niklas Bruse, Jonathan Dörr, Andreas Dräger, Gunnar Elke, David Ellinghaus, Julia Fischer, Michael Forster, Andre Franke, Sören Franzenburg, Norbert Frey, Anette Friedrichs, Janina Fuß, Andreas Glück, Jacob Hamm, Finn Hinrichsen, Marc P. Hoeppner, Simon Imm, Ralf Junker, Sina Kaiser, Ying H. Kan, Rainer Knoll, Christoph Lange, Georg Laue, Clemens Lier, Matthias Lindner, Georgios Marinos, Robert Markewitz, Jacob Nattermann, Rainer Noth, Peter Pickkers, Klaus F. Rabe, Alina Renz, Christoph Röcken, Jan Rupp, Annika Schaffarzyk, Alexander Scheffold, Jonas Schulte-Schrepping, Domagoj Schunk, Dirk Skowasch, Thomas Ulas, Klaus-Peter Wandinger, Michael Wittig, Johannes Zimmermann, Hauke Busch, Bimba F. Hoyer, Christoph Kaleta, Jan Heyckendorf, Matthijs Kox, Jan Rybniker, Stefan Schreiber, Joachim L. Schultze, Philip Rosenstiel, Nicholas E. Banovich, Tushar Desai, Oliver Eickelberg, Muzlifa Haniffa, Peter Horvath, Jonathan A. Kropski, Robert Lafyatis, Joakim Lundeberg, Kerstin Meyer, Martijn C. Nawijn, Marko Nikolic, Jose Ordovas Montanes, Dana Pe’er, Purushothama Rao Tata, Emma Rawlins, Aviv Regev, Paul Reyfman, Christos Samakovlis, Joachim Schultze, Alex Shalek, Douglas Shepherd, Jason Spence, Sarah Teichmann, Fabian Theis, Alexander Tsankov, Maarten van den Berge, Michael von Papen, Jeffrey Whitsett, Laure Emmanuelle Zaragosi, Angel Angelov, Robert Bals, Alexander Bartholomäus, Anke Becker, Daniela Bezdan, Ezio Bonifacio, Peer Bork, Thomas Clavel, Maria Colme-Tatche, Andreas Diefenbach, Alexander Dilthey, Nicole Fischer, Konrad Förstner, Julia-Stefanie Frick, Julien Gagneur, Alexander Goesmann, Torsten Hain, Michael Hummel, Stefan Janssen, Jörn Kalinowski, René Kallies, Birte Kehr, Andreas Keller, Sarah Kim-Hellmuth, Christoph Klein, Oliver Kohlbacher, Jan O. Korbel, Ingo Kurth, Markus Landthaler, Yang Li, Kerstin Ludwig, Oliwia Makarewicz, Manja Marz, Alice McHardy, Christian Mertes, Markus Nöthen, Peter Nürnberg, Uwe Ohler, Stephan Ossowski, Jörg Overmann, Silke Peter, Klaus Pfeffer, Anna R. Poetsch, Alfred Pühler, Niklaus Rajewsky, Markus Ralser, Olaf Rieß, Stephan Ripke, Ulisses Nunes da Rocha, Philip Rosenstiel, Antoine-Emmanuel Saliba, Leif Erik Sander, Birgit Sawitzki, Philipp Schiffer, Eva-Christina Schulte, Joachim L. Schultze, Alexander Sczyrba, Oliver Stegle, Jens Stoye, Fabian Theis, Janne Vehreschild, Jörg Vogel, Max von Kleist, Andreas Walker, Jörn Walter, Dagmar Wieczorek, John Ziebuhr
Journal: Immunity (2020)
Treatment Sequencing for Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer
Authors: Diego Kauffmann-Guerrero, Kathrin Kahnert, Rudolf M. Huber
Journal: Drugs (2020)

Non-small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases and is the leading cause of cancer-related deaths. Most NSCLC patients are diagnosed with advanced disease and require systemic treatment. Despite emerging advances in chemotherapy and immunotherapy, the prognosis of stage IV patients remains poor. However, the discovery of oncogenic driver mutations including mutations in the epidermal growth factor receptor (EGFR), the anaplastic lymphoma kinase (ALK) and others, characterize a subset of patients with the opportunity of targeted therapies. Fusions between the ALK and echinoderm microtubule-associated protein-like 4 (EML4) are present in ∼ 3–5% of patients with NSCLC. Several first-, second-, and third-generation ALK tyrosine kinase inhibitors (TKIs) have been developed in the last decade and have tremendously changed treatment options and outcomes of ALK-positive NSCLC patients. With increasing treatment options, treatment sequence decisions have become more and more complex. ALK-mutations, fusion variants, or activation of by-pass pathways result in treatment resistance during the course of treatment in nearly all patients. Mutation-guided treatment sequencing can lead to better outcomes, and re-biopsy or liquid-biopsy should be performed whenever possible in case of disease progression in ALK-rearranged patients. In the future, combinational treatment of ALK TKIs with other pathway-inhibitors might further improve patients' treatment options and outcomes. Here, we review the data for currently available ALK TKIs, discuss approaches of treatment sequencing, and give an outlook on emerging developments.
Predicting the risk of developing diabetic retinopathy using deep learning
Authors: Ashish Bora, Siva Balasubramanian, Boris Babenko, Sunny Virmani, Subhashini Venugopalan, Akinori Mitani, Guilherme de Oliveira Marinho, Jorge Cuadros, Paisan Ruamviboonsuk, Greg S Corrado, Lily Peng, Dale R Webster, Avinash V Varadarajan, Naama Hammel, Yun Liu, Pinal Bavishi
Journal: The Lancet Digital Health (2020)

BackgroundDiabetic retinopathy screening is instrumental to preventing blindness, but scaling up screening is challenging because of the increasing number of patients with all forms of diabetes. We aimed to create a deep-learning system to predict the risk of patients with diabetes developing diabetic retinopathy within 2 years.MethodsWe created and validated two versions of a deep-learning system to predict the development of diabetic retinopathy in patients with diabetes who had had teleretinal diabetic retinopathy screening in a primary care setting. The input for the two versions was either a set of three-field or one-field colour fundus photographs. Of the 575 431 eyes in the development set 28 899 had known outcomes, with the remaining 546 532 eyes used to augment the training process via multitask learning. Validation was done on one eye (selected at random) per patient from two datasets: an internal validation (from EyePACS, a teleretinal screening service in the USA) set of 3678 eyes with known outcomes and an external validation (from Thailand) set of 2345 eyes with known outcomes.FindingsThe three-field deep-learning system had an area under the receiver operating characteristic curve (AUC) of 0·79 (95% CI 0·77–0·81) in the internal validation set. Assessment of the external validation set—which contained only one-field colour fundus photographs—with the one-field deep-learning system gave an AUC of 0·70 (0·67–0·74). In the internal validation set, the AUC of available risk factors was 0·72 (0·68–0·76), which improved to 0·81 (0·77–0·84) after combining the deep-learning system with these risk factors (p<0·0001). In the external validation set, the corresponding AUC improved from 0·62 (0·58–0·66) to 0·71 (0·68–0·75; p<0·0001) following the addition of the deep-learning system to available risk factors.InterpretationThe deep-learning systems predicted diabetic retinopathy development using colour fundus photographs, and the systems were independent of and more informative than available risk factors. Such a risk stratification tool might help to optimise screening intervals to reduce costs while improving vision-related outcomes.FundingGoogle.
Relationship between baseline cardiac biomarkers and cardiovascular death or hospitalization for heart failure with and without sodium–glucose co‐transporter 2 inhibitor therapy in <scp>DECLARE‐TIMI</scp> 58
Authors: Thomas A. Zelniker, David A. Morrow, Ofri Mosenzon, Erica L. Goodrich, Petr Jarolim, Sabina A. Murphy, Deepak L. Bhatt, Lawrence A. Leiter, Darren K. McGuire, John Wilding, Christoph Bode, Basil S. Lewis, Ingrid Gause‐Nilsson, Anna Maria Langkilde, Martin Fredriksson, Itamar Raz, Marc S. Sabatine, Stephen D. Wiviott
Journal: European Journal of Heart Failure (2020)
Molecularly engineered truncated tissue factor with therapeutic aptamers for tumor-targeted delivery and vascular infarction
Authors: Bozhao Li, Jingyan Wei, Chunzhi Di, Zefang Lu, Feilong Qi, Yinlong Zhang, Wei Sun Leong, Lele Li, Guangjun Nie, Suping Li
Journal: Acta Pharmaceutica Sinica B (2020)

Selective occlusion of tumor vasculature has proven to be an effective strategy for cancer therapy. Among vascular coagulation agents, the extracellular domain of coagulation-inducing protein tissue factor, truncated tissue factor (tTF), is the most widely used. Since the truncated protein exhibits no coagulation activity and is rapidly cleared in the circulation, free tTF cannot be used for cancer treatment on its own but must be combined with other moieties. We here developed a novel, tumor-specific tTF delivery system through coupling tTF with the DNA aptamer, AS1411, which selectively binds to nucleolin receptors overexpressing on the surface of tumor vascular endothelial cells and is specifically cytotoxic to target cells. Systemic administration of the tTF-AS1411 conjugates into tumor-bearing animals induced intravascular thrombosis solely in tumors, thus reducing tumor blood supply and inducing tumor necrosis without apparent side effects. This conjugate represents a uniquely attractive candidate for the clinical translation of vessel occlusion agent for cancer therapy.
Global burden of acute lower respiratory infection associated with human metapneumovirus in children under 5 years in 2018: a systematic review and modelling study
Authors: Xin Wang, You Li, Maria Deloria-Knoll, Shabir A Madhi, Cheryl Cohen, Asad Ali, Sudha Basnet, Quique Bassat, W Abdullah Brooks, Malinee Chittaganpitch, Marcela Echavarria, Rodrigo A Fasce, Doli Goswami, Siddhivinayak Hirve, Nusrat Homaira, Stephen R C Howie, Karen L Kotloff, Najwa Khuri-Bulos, Anand Krishnan, Marilla G Lucero, Socorro Lupisan, Ainara Mira-Iglesias, David P Moore, Cinta Moraleda, Marta Nunes, Histoshi Oshitani, Betty E Owor, Fernando P Polack, Katherine L O'Brien, Zeba A Rasmussen, Barbara A Rath, Vahid Salimi, J Anthony G Scott, Eric A F Simões, Tor A Strand, Donald M Thea, Florette K Treurnicht, Linda C Vaccari, Lay-Myint Yoshida, Heather J Zar, Harry Campbell, Harish Nair, Romina Libster, Grieven Otieno, Imane Joundi, Shobha Broor, Mark Nicol, Ritvik Amarchand, Ting Shi, F. Xavier López-Labrador, Julia M. Baker, Alexandra Jamison, Avinash Choudekar, Sanjay Juvekar, Patrick Obermeier, Brunhilde Schweiger, Lola Madrid, Elizabeth Thomas, Miguel Lanaspa, Hanna Nohynek, James Nokes, Marta Werner, Anh Danhg, Mandeep Chadha, Joan Puig-Barberà, Mauricio T. Caballero, Maria Mathisen, Sibongile Walaza, Orienka Hellferscee, Matt Laubscher, Melissa M. Higdon, Meredith Haddix, Pongpun Sawatwong, Henry C. Baggett, Phil Seidenberg, Lawrence Mwanayanda, Martin Antonio, Bernard E. Ebruke, Tanja Adams, Mustafizur Rahman, Mohammed Ziaur Rahman, Samboa O. Sow, Vicky L. Baillie, Lesley Workman, Michiko Toizumi, Milagritos D. Tapia, Thi hien anh Nguyen, Susan Morpeth
Journal: The Lancet Global Health (2020)

Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years.
Abstract PO-079: COVID-19 in relation to hematologic events and mortality in subset of inpatient cancer patients
Authors: Saikrishna Gadde, Ambuga Badari, John Cole, Nikhil Manjunath
Journal: Clinical Cancer Research (2020)

Abstract COVID-19 is a newly diagnosed entity that has been identified for about 6 months. With the US now being the prevalent nation affected, we aimed to identify factors that were relevant to survival and hematologic events in COVID patients. Our group had primarily been assessing COVID-19-confirmed patients as per PCR at Ochsner Medical Center in Louisiana; we primarily studied patients who were admitted between January 2020 to May 2020. Main events that are currently being studied include factors such as mortality, length of stay, and bleeding or thrombotic events. Secondary endpoints included factors such as influence on blood type and also amount of transfusions required by these patients. Our overall analysis of 1,773 patients yielded a number of 60 patients whom we were able to identify as having an active cancer diagnosis. This disproportionate number of patients may be related to factors such as reluctance to visit the hospital among cancer patients, a phenomenon noted similarly in Cardiology, where the number of admissions for cardiac causes had declined suddenly during this pandemic timeline. One half of our population was African American and included an even proportion of males and females. The age range of patients was between 35-93 years. The most common malignancies that were noted to co-occur with COVID-19 in our population seemed to be lung, prostate, and hematologic malignancies. Although final analyses regarding mortality are to be completed, the proportion of patients who had died with a diagnosis of cancer was around 50% per collection of our current data. Twenty three out of 60 (38%) patients required blood transfusions. In comparison to other reports that had reported bleeding events and thrombotic events, our report revealed a much lower rate of bleeding events (5/60) and thrombotic events (5/60). We plan to repeat our analysis to assess for any confounders in identifying these events, as noted, since some earlier literature had reported between one quarter to two thirds of patients having a thrombotic event. Our analysis also looks at other descriptive variables such as use of anticoagulant and antiplatelet agents, absolute counts of neutrophils and lymphocytes, platelets, and coagulation markers. Also, our assessment includes a study in assessment of any delays noted in chemotherapy dates for these patients. Citation Format: Saikrishna Gadde, Ambuga Badari, John Cole, Nikhil Manjunath. COVID-19 in relation to hematologic events and mortality in subset of inpatient cancer patients [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-079.
Sedentary Behavior and Diabetes Risk Among Women Over the Age of 65 Years: The OPACH Study
Authors: John Bellettiere, Michael J. LaMonte, Genevieve N. Healy, Sandy Liles, Kelly R. Evenson, Chongzhi Di, Jacqueline Kerr, I-Min Lee, Eileen Rillamas-Sun, David Buchner, Melbourne F. Hovell, Andrea Z. LaCroix
Journal: Diabetes Care (2020)

To evaluate whether sedentary time (ST) and/or sedentary behavior patterns are related to incident diabetes in the U.S.'s oldest age-groups.
Combination Therapy of Killing Diseases by Injectable Hydrogels: From Concept to Medical Applications
Authors: Fatemeh Poustchi, Hamed Amani, Zainab Ahmadian, Seyyed Vahid Niknezhad, Soraya Mehrabi, Hélder A. Santos, Mohammad‐Ali Shahbazi
Journal: Advanced Healthcare Materials (2020)

Abstract The complexity of hard‐to‐treat diseases strongly undermines the therapeutic potential of available treatment options. Therefore, a paradigm shift from monotherapy toward combination therapy has been observed in clinical research to improve the efficiency of available treatment options. The advantages of combination therapy include the possibility of synchronous alteration of different biological pathways, reducing the required effective therapeutic dose, reducing drug resistance, and lowering the overall costs of treatment. The tunable physical properties, excellent biocompatibility, facile preparation, and ease of administration with minimal invasiveness of injectable hydrogels (IHs) have made them excellent candidates to solve the clinical and pharmacological limitations of present systems for multitherapy by direct delivery of therapeutic payloads and improving therapeutic responses through the formation of depots containing drugs, genes, cells, or a combination of them in the body after a single injection. In this review, currently available methods for the design and fabrication of IHs are systematically discussed in the first section. Next, as a step toward establishing IHs for future multimodal synergistic therapies, recent advances in cancer combination therapy, wound healing, and tissue engineering are addressed in detail in the following sections. Finally, opportunities and challenges associated with IHs for multitherapy are listed and further discussed.
Steering cell behavior through mechanobiology in 3D: A regenerative medicine perspective
Authors: Jip Zonderland, Lorenzo Moroni
Journal: Biomaterials (2020)

Mechanobiology, translating mechanical signals into biological ones, greatly affects cellular behavior. Steering cellular behavior for cell-based regenerative medicine approaches requires a thorough understanding of the orchestrating molecular mechanisms, among which mechanotransducive ones are being more and more elucidated. Because of their wide use and highly mechanotransduction dependent differentiation, this review focuses on mesenchymal stromal cells (MSCs), while also briefly relating the discussed results to other cell types. While the mechanotransduction pathways are relatively well-studied in 2D, much remains unknown of the role and regulation of these pathways in 3D. Ultimately, cells need to be cultured in a 3D environment to create functional de novo tissue. In this review, we explore the literature on the roles of different material properties on cellular behavior and mechanobiology in 2D and 3D. For example, while stiffness plays a dominant role in 2D MSCs differentiation, it seems to be of subordinate importance in 3D MSCs differentiation, where matrix remodeling seems to be key. Also, the role and regulation of some of the main mechanotransduction players are discussed, focusing on MSCs. We have only just begun to fundamentally understand MSCs and other stem cells behavior in 3D and more fundamental research is required to advance biomaterials able to replicate the stem cell niche and control cell activity. This better understanding will contribute to smarter tissue engineering scaffold design and the advancement of regenerative medicine.
日本人患者の頚動脈内膜中膜複合体厚の進行に対するロスバスタチンを用いた集中的脂質低下療法の効果 アテローム性動脈硬化症緩解治療の正当化(JART)試験
Authors: Nohara Ryuji, Daida Hiroyuki, Hata Mitsumasa, Kaku Kohei, Kawamori Ryuzo, Kishimoto Junji, Kurabayashi Masahiko, Masuda Izuru, Sakuma Ichiro, Yamazaki Tsutomu, Yokoi Hiroyoshi, Yoshida Masayuki
Journal: Circulation (2012)
STAT3 and TP53 mutations associate with poor prognosis in anaplastic large cell lymphoma
Authors: Cosimo Lobello, Boris Tichy, Vojtech Bystry, Lenka Radova, Daniel Filip, Marek Mraz, Ivonne-Aidee Montes-Mojarro, Nina Prokoph, Hugo Larose, Huan-Chang Liang, Geeta G. Sharma, Luca Mologni, David Belada, Katerina Kamaradova, Falko Fend, Carlo Gambacorti-Passerini, Olaf Merkel, Suzanne D. Turner, Andrea Janikova, Sarka Pospisilova
Journal: Leukemia (2020)

Systemic anaplastic large cell lymphoma (sALCL) encompasses two distinct clinical entities of T-cell non-Hodgkin lymphoma: anaplastic lymphoma kinase-positive (ALK+) ALCL and ALK-negative (ALK-) ALCL. These entities are characterized by either the presence or absence of an ALK translocation. It has been reported that ALK+ ALCL has a better prognosis compared to ALK-, with a 5-year overall survival (OS) of 70–80% versus 40–60%, respectively, [1,2,3]. Furthermore, more than 30% of ALK+ ALCL patients relapse [4, 5]. Despite the distinction between the two sALCL subtypes, frontline treatment for adults is similar and is based on CHOP or CHOEP, instead pediatric ALCL patients are mainly treated following the ALCL99 protocol [6,7,8]. Whilst high-throughput genomic studies in sALCL have shown recurrent genetic alterations, their association with outcome has not been fully investigated [9,10,11,12,13]. In this study, the mutational landscape of sALCL patient tumors was investigated to discover potential biomarkers that may improve risk stratification and patient management.
The new normal
Authors: Nikki Nabavi
Journal: BMJ (2020)

This year everyone has had to adjust to changes in every aspect of their lives. Medical students have not been immune. Since the start of the pandemic, medical students have been hard hit by the knock-on effects of covid-19 disruption,” commented a member of the BMA medical student committee—for example, problems booking exams for final year UK medical students,1 decreased funding for UK medical schools,2 or student areas themselves being virus hotspots.3

In September medical students found themselves returning to clinical placements after a long break as a result of disruptions to learning from the covid-19 pandemic. Laura Nunez-Mulder, Mahmoud Elbahnasawi, and Saakshi Bansal share …
Low-Avidity CD4+ T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19
Authors: Petra Bacher, Elisa Rosati, Daniela Esser, Gabriela Rios Martini, Carina Saggau, Esther Schiminsky, Justina Dargvainiene, Ina Schröder, Imke Wieters, Yascha Khodamoradi, Fabian Eberhardt, Maria J.G.T. Vehreschild, Holger Neb, Michael Sonntagbauer, Claudio Conrad, Florian Tran, Philip Rosenstiel, Robert Markewitz, Klaus-Peter Wandinger, Max Augustin, Jan Rybniker, Matthias Kochanek, Frank Leypoldt, Oliver A. Cornely, Philipp Koehler, Andre Franke, Alexander Scheffold
Journal: Immunity (2020)
Efficacy and safety of ledipasvir/sofosbuvir in 5,028 Mongolian patients infected with genotype 1 hepatitis C virus: A multicenter study
Authors: Oidov Baatarkhuu, Jae Seung Lee, Jazag Amarsanaa, Do Young Kim, Sang Hoon Ahn, Nyamsuren Naranzul, Damba Enkhtuya, Nagir Choijamts, Purev Batbayar, Radnaa Otgonbayar, Bat-Ulzii Saruul, Chuluunbaatar Gantuul, Baljinnyam Gegeebadrakh, Narangerel Tuvshinbayar, Dorjgotov Badamsuren, Galsan Ulzmaa, Jamiyandorj Otgonbold, Kwang-Hyub Han
Journal: Clinical and Molecular Hepatology (2020)

Background/Aims: Ledipasvir/sofosbuvir (LDV/SOF) shows high efficacy and safety in patients with genotype 1-hepatitis C virus (HCV). We aimed to investigate the efficacy and safety of LDV/SOF in real-world Mongolian patients.Methods: Between 2015 to 2019, 23 (0.5%) and 5,005 patients (99.5%) with genotype 1a and 1b HCV, respectively, were treated with a fixed-dose tablet containing 90 mg ledipasvir and 400 mg sofosbuvir for 12 weeks, and 81 patients (1.6%) with previous experience of interferon (IFN)-based treatment received additional 1,000 mg ribavirin. HCV RNA was measured at 4, 12, and 24 weeks after the first dose to determine rapid virologic response, end of treatment response (ETR), and sustained virologic response at 12 weeks after end of treatment (SVR12).Results: Most patients (n=5,008; 99.6%) achieved ETR and SVR12 without virologic relapse. Patients with genotype 1a showed low rates of ETR and SVR12 in only 16 patients (69.6%). There was no significant difference in SVR12 rate between patients regardless of IFN experience (n=81; 1.6%), cirrhosis (n=1,151; 22.9%), HCV RNA &gt;6×10&lt;sup&gt;6&lt;/sup&gt; IU/mL (n=866; 17.2%), or liver stiffness &gt;9.6 kPa (n=1,721; 34.2%) (100.0%, 99.3%, 99.4%, and 99.4%, respectively). No severe adverse events (AEs) were reported, and there was no dose reduction or interruption due to AE. The most common AEs were headache (n=472; 9.4%), fatigue (n=306; 6.2%), abdominal discomfort (n=295; 5.9%), and skin rash (n=141; 2.8%).Conclusions: LDV/SOF showed high efficacy and safety for patients with genotype 1, especially 1b HCV, in Mongolia. The real-world data might be applicable to patients in other Asian-Pacific countries.