tbuckley/cabot-search huggingface dataset:
Biofabrication of Hepatic Constructs by 3D Bioprinting of a Cell‐Laden Thermogel: An Effective Tool to Assess Drug‐Induced Hepatotoxic Response
Authors: Manuele Gori, Sara M. Giannitelli, Miranda Torre, Pamela Mozetic, Franca Abbruzzese, Marcella Trombetta, Enrico Traversa, Lorenzo Moroni, Alberto Rainer
Journal: Advanced Healthcare Materials (2020)

Abstract A thermoresponsive Pluronic/alginate semisynthetic hydrogel is used to bioprint 3D hepatic constructs, with the aim to investigate liver‐specific metabolic activity of the 3D constructs compared to traditional 2D adherent cultures. The bioprinting method relies on a bioinert hydrogel and is characterized by high‐shape fidelity, mild depositing conditions and easily controllable gelation mechanism. Furthermore, the dissolution of the sacrificial Pluronic templating agent significantly ameliorates the diffusive properties of the printed hydrogel. The present findings demonstrate high viability and liver‐specific metabolic activity, as assessed by synthesis of urea, albumin, and expression levels of the detoxifying CYP1A2 enzyme of cells embedded in the 3D hydrogel system. A markedly increased sensitivity to a well‐known hepatotoxic drug (acetaminophen) is observed for cells in 3D constructs compared to 2D cultures. Therefore, the 3D model developed herein may represent an in vitro alternative to animal models for investigating drug‐induced hepatotoxicity.
The Impact of COVID-19 on Clinical Trial Execution at the Dana-Farber Cancer Institute
Authors: Sara M Tolaney, Christine A Lydon, Tianyu Li, Jiale Dai, Andrea Standring, Kristen A Legor, Caryn M Caparrotta, Matthew P Schenker, Daniel I Glazer, Nabihah Tayob, Steven G DuBois, Jeffrey A Meyerhardt, Mary-Ellen Taplin, Bruce E Johnson
Journal: JNCI Journal of the National Cancer Institute (2020)

Interventions designed to limit the spread of coronavirus disease 2019 (COVID-19) are having profound effects on the delivery of health care, but data showing the impact on oncology clinical trial enrollment, treatment, and monitoring are limited. We prospectively tracked relevant data from oncology clinical trials at Dana-Farber Cancer Institute from January 1, 2018, to June 30, 2020, including the number of open trials, new patient enrollments, in-person and virtual patient visits, dispensed investigational infusions, dispensed or shipped oral investigational agents, research biopsies, and blood samples. We ascertained why patients came off trials and determined on-site clinical research staffing levels. We used 2-sided Wilcoxon rank sum tests to assess the statistical significance of the reported changes. Nearly all patients on interventional treatment trials were maintained, and new enrollments continued at just under one-half the prepandemic rate. The median number of investigational prescriptions shipped to patients increased from 0 to 74 (range = 22-107) per week from March to June 2020. The median number of telemedicine appointments increased from 0 to 107 (range = 33-267) per week from March to June 2020. Research biopsies and blood collections decreased dramatically after Dana-Farber Cancer Institute implemented COVID-19-related policies in March 2020. The number of research nurses and clinical research coordinators on site also decreased after March 2020. Substantial changes were required to safely continue clinical research during the pandemic, yet we observed no increases in serious adverse events or major violations related to drug dosing. Lessons learned from adapting research practices during COVID-19 can inform industry sponsors and governmental agencies to consider altering practices to increase operational efficiency and convenience for patients.
Steering Chimeric Antigen Receptor T Cells Into the Hodgkin Lymphoma Niche
Authors: Paul J. Bröckelmann, Sven Borchmann, Peter Borchmann, Andreas Engert
Journal: Journal of Clinical Oncology (2020)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. July 23, 2020 ARTICLE CITATION DOI: 10.1200/JCO.20.02351 Journal of Clinical Oncology - published online before print September 18, 2020 PMID: 32946351 Steering Chimeric Antigen Receptor T Cells Into the Hodgkin Lymphoma Niche Paul J. Bröckelmann, MD1xPaul J. BröckelmannSearch for articles by this author; Sven Borchmann, MD1xSven BorchmannSearch for articles by this author; Peter Borchmann, MD, PhD1xPeter BorchmannSearch for articles by this author; and Andreas Engert, MD1xAndreas EngertSearch for articles by this author Show More 1Department I of Internal Medicine, Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf, and German Hodgkin Study Group, University of Cologne, Cologne, GermanySee accompanying article on page 3794 https://doi.org/10.1200/JCO.20.02351 First Page Full Text PDF Figures and Tables © 2020 by American Society of Clinical Oncology Companion Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma
Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial
Authors: Maryam Edalatifard, Maryam Akhtari, Mohammadreza Salehi, Zohre Naderi, Ahmadreza Jamshidi, Shayan Mostafaei, Seyed Reza Najafizadeh, Elham Farhadi, Nooshin Jalili, Masoud Esfahani, Besharat Rahimi, Hossein Kazemzadeh, Maedeh Mahmoodi Aliabadi, Tooba Ghazanfari, Mohammadreza Sattarian, Hourvash Ebrahimi Louyeh, Seyed Reza Raeeskarami, Saeidreza Jamalimoghadamsiahkali, Nasim Khajavirad, Mahdi Mahmoudi, Abdolrahman Rostamian
Journal: European Respiratory Journal (2020)

There are no determined treatment agents for severe COVID-19. It is suggested that methylprednisolone, as an immunosuppressive treatment, can reduce the inflammation of the respiratory system in COVID-19 patients.We conducted a single-blind, randomised controlled clinical trial involving severe hospitalised patients with confirmed COVID-19 at the early pulmonary phase of the illness in Iran. The patients were randomly allocated in a 1:1 ratio by the block randomisation method to receive standard care with methylprednisolone pulse (intravenous injection, 250 mg·day-1 for 3 days) or standard care alone. The study end-point was the time of clinical improvement or death, whichever came first. Primary and safety analysis was done in the intention-to-treat (ITT) population.68 eligible patients underwent randomisation (34 patients in each group) from April 20, 2020 to June 20, 2020. In the standard care group, six patients received corticosteroids by the attending physician before the treatment and were excluded from the overall analysis. The percentage of improved patients was higher in the methylprednisolone group than in the standard care group (94.1% versus 57.1%) and the mortality rate was significantly lower in the methylprednisolone group (5.9% versus 42.9%; p<0.001). We demonstrated that patients in the methylprednisolone group had a significantly increased survival time compared with patients in the standard care group (log-rank test: p<0.001; hazard ratio 0.293, 95% CI 0.154-0.556). Two patients (5.8%) in the methylprednisolone group and two patients (7.1%) in the standard care group showed severe adverse events between initiation of treatment and the end of the study.Our results suggest that methylprednisolone pulse could be an efficient therapeutic agent for hospitalised severe COVID-19 patients at the pulmonary phase.
Geographic Distribution of US Cohorts Used to Train Deep Learning Algorithms
Authors: Amit Kaushal, Russ Altman, Curt Langlotz
Journal: JAMA (2020)

This study describes the US geographic distribution of patient cohorts used to train deep learning algorithms in published radiology, ophthalmology, dermatology, pathology, gastroenterology, and cardiology machine learning articles published in 2015-2019.
Six month maintenance therapy with 10 mg clevudine maintains the viral suppression and biochemical improvement achieved with six months therapy with 30 mg
Authors: Young Hwa Chung, Kwan Sik Lee, Ju Hyun Kim, Soo Hyung Ryu, Seung Woon Paik, Soon Ho Um, Byung Hoon Han, Mong Cho, Kwan Soo Byun, Byung Ik Kim, Joong-Won Park, Heon Ju Lee, Joon-Yeol Han, Seong Gyu Hwang, Haak Cheoul Kim, Kwon Yoo, Young Suk Lee, Youn Jae Lee, Young Soo Kim, Jin Mo Yang, Chae Yoon Chon, Se Hyun Cho, Sung Kyu Choi, Hyo-Suk Lee, Byung Chul Yoo
Journal: Hepatology (2018)
Ultrasmall Ternary FePtMn Nanocrystals with Acidity‐Triggered Dual‐Ions Release and Hypoxia Relief for Multimodal Synergistic Chemodynamic/Photodynamic/Photothermal Cancer Therapy
Authors: Baochan Yang, Zhichao Dai, Gaorui Zhang, Zunfu Hu, Xiuxiu Yao, Shan Wang, Qingyun Liu, Xiuwen Zheng
Journal: Advanced Healthcare Materials (2020)

Abstract Multimodal imaging‐guided synergistic anticancer strategies have attracted increasing attention for efficient diagnosis and therapy of cancer. Herein, a multifunctional nanotheranostic agent FePtMn‐Ce6/FA (FPMCF NPs) is constructed by covalently anchoring photosensitizer chlorin e6 (Ce6) and targeting molecule folic acid (FA) on ultrasmall homogeneous ternary FePtMn nanocrystals. Response to tumor microenvironment (TME), FPMCF NPs can release Fe 2+ to catalyze H 2 O 2 into •OH by Fenton reaction and simultaneously catalyze hydrogen peroxide (H 2 O 2 ) into O 2 to overcome the tumor hypoxia barrier. Released O 2 is further catalyzed into 1 O 2 under 660 nm laser irradiation with Ce6. Thus, the FPMCF NPs exhibit superior dual‐ROS oxidization capability including ferroptosis chemodynamic oxidization and 1 O 2 ‐based photodynamic oxidization. Interestingly, FPMCF NPs reveal strong photothermal conversion efficiency exposed to an 808 nm laser, which can assist dual‐ROS oxidization to suppress solid tumor remarkably. Additionally, Mn 2+ can be released from FPMCF NPs to enhance longitudinal relaxivity (T 1 ‐weighted magnetic resonance (MR) imaging) and Fe‐synergistic transverse relaxivity (T 2 ‐weighted MR imaging), which is convenient for diagnosis of solid tumors. Meanwhile, the fluorescent/photothermal (FL/PT) imaging function of FPMCF NPs can also accurately monitor tumor location. Therefore, FPMCF NPs with multimodal MR/FL/PT imaging‐guided synergistic chemodynamic/photodynamic/photothermal cancer therapy capability have potential bioapplication in bionanomedicine field.
Obituary for Sanjiv Sam Gambhir, MD, PhD
Authors: Guido Davidzon, Benjamin Franc, Carina Mari Aparici, Farshad Moradi, Judy Nguyen, Andrei Iagaru
Journal: Clinical Nuclear Medicine (2020)

Davidzon, Guido MD; Franc, Benjamin MD; Mari Aparici, Carina MD; Moradi, Farshad MD, PhD; Nguyen, Judy MD; Iagaru, Andrei MD Author Information
Priorities in reducing child mortality: Azithromycin and other interventions
Authors: David Mabey, Uduak Okomo, Brian Greenwood
Journal: PLoS Medicine (2020)

According to World Health Organization (WHO) estimates, the global under-5 mortality rate decreased by 59% between 1990 and 2018, from 93 to 39 deaths per 1,000 live births [1].This remarkable reduction was achieved largely by increasing the coverage of vaccination against measles and other childhood infections, rolling out new vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b, and introducing artemisinin combination treatment and long-lasting, insecticide-treated bed nets for the treatment and prevention of malaria.In 2018, a randomised trial conducted in Niger, Tanzania, and Malawi-the Macrolides Oraux pour Re ´duire les De ´cès avec un Oeil sur la Re ´sistance (MORDOR; "Oral macrolides to reduce death with an eye on resistance") study-showed that twice yearly, community-based mass treatment with a single dose of azithromycin reduced all-cause under-5 mortality by 13.5% (95% CI 6.7-19.8)[2].In children aged between 1 and 6 months, mortality was 24.9% lower in those who received azithromycin.Azithromycin is a long-acting, broad spectrum antibiotic that also has antimalarial, anti-inflammatory, and possibly antiviral properties [3,4].At the study site in Niger, where the impact of azithromycin on mortality was greatest, verbal autopsy revealed fewer deaths from malaria, dysentery, meningitis, and pneumonia in communities treated with azithromycin, the prevalence of malaria parasitaemia was reduced, and the gut pathogen load was reduced after the fourth biannual azithromycin distribution [5][6][7].Given that severe malnutrition increases the risk of life-threatening infectious diseases and is an important contributor to under-5 mortality, it seemed likely that the impact of azithromycin on mortality would be enhanced in malnourished children.The paper by Kieran O'Brien and colleagues in this issue of PLOS Medicine investigates the question, comparing the impact of azithromycin mass treatment in malnourished (underweight) versus well-nourished children at the Niger study site of MORDOR [8].The reduction in mortality in the azithromycin arm of the study (12.6 fewer deaths, 95% CI 6.9-18.5, per 1,000 person-years overall) was greater in malnourished than in well-nourished children, but not significantly so.The authors conclude that azithromycin mass treatment given to all children will have a greater impact on mortality than targeting treatment to malnourished children.While this is not unexpected, the potential impact of treating 10 times as many children on the antimicrobial susceptibility of important bacterial pathogens is an important consideration.Bacterial infections remain a major cause of mortality among newborns [9] with Staphylococcus aureus, S. pneumoniae, and group B streptococcus (GBS) among the major pathogens [10].Although the MORDOR trial excluded newborns, a recent study showed that
Characterization of Stromal Tumor-infiltrating Lymphocytes and Genomic Alterations in Metastatic Lobular Breast Cancer
Authors: François Richard, Samira Majjaj, David Venet, Françoise Rothé, Julien Pingitore, Bram Boeckx, Caterina Marchio, Florian Clatot, François Bertucci, Odette Mariani, Christine Galant, Gert van den Eynden, Roberto Salgado, Elia Biganzoli, Diether Lambrechts, Anne Vincent-Salomon, Giancarlo Pruneri, Denis Larsimont, Christos Sotiriou, Christine Desmedt
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Invasive lobular carcinoma (ILC) represents the second most common histologic breast cancer subtype after invasive ductal carcinoma (IDC). While primary ILC has been extensively studied, metastatic ILC has been poorly characterized at the genomic and immune level. Experimental Design: We retrospectively assembled the multicentric EuroILC series of matched primary and metastatic samples from 94 patients with estrogen receptor (ER)-positive ILC. Stromal tumor-infiltrating lymphocytes (sTILs) were assessed by experienced pathologists. Targeted sequencing and low pass whole-genome sequencing were conducted to detect mutations and copy-number aberrations (CNAs). We compared the frequencies of the alterations in EuroILC with those from patients with ER-positive metastatic ILC (n = 135) and IDC (n = 563) from MSK-IMPACT. Results: Low sTIL levels were observed in ILC metastases, with higher levels in the mixed nonclassic histology. Considering ILC metastases from EuroILC and MSK-IMPACT, we observed that &amp;gt;50% of tumors harbor genomic alterations that have previously been associated with endocrine resistance. A matched primary/metastasis comparison in EuroILC revealed mutations (AKT1, ARID1A, ESR1, ERBB2, or NF1) and CNAs (PTEN or NF1 deletion, CYP19A1 amplification) associated with endocrine resistance that were private to the metastasis in 22% (7/32) and 19% (4/21) of patients, respectively. An increase in CDH1, ERBB2, FOXA1, and TBX3 mutations, in CDH1 deletions and a decrease in TP53 mutations was observed in ILC as compared with IDC metastases. Conclusions: ILC metastases harbor genomic alterations that may potentially explain endocrine resistance in a large proportion of patients, and present genomic differences as compared with IDC metastases.
Implantable Nanosensors for Human Steroid Hormone Sensing In Vivo Using a Self‐Templating Corona Phase Molecular Recognition
Authors: Michael A. Lee, Song Wang, Xiaojia Jin, Naveed Ali Bakh, Freddy T. Nguyen, Juyao Dong, Kevin S. Silmore, Xun Gong, Crystal Pham, Kelvin K. Jones, Sureshkumar Muthupalani, Gili Bisker, Manki Son, Michael S. Strano
Journal: Advanced Healthcare Materials (2020)

Abstract Dynamic measurements of steroid hormones in vivo are critical, but steroid sensing is currently limited by the availability of specific molecular recognition elements due to the chemical similarity of these hormones. In this work, a new, self‐templating synthetic approach is applied using corona phase molecular recognition (CoPhMoRe) targeting the steroid family of molecules to produce near infrared fluorescent, implantable sensors. A key limitation of CoPhMoRe has been its reliance on library generation for sensor screening. This problem is addressed with a self‐templating strategy of polymer design, using the examples of progesterone and cortisol sensing based on a styrene and acrylic acid copolymer library augmented with an acrylated steroid. The pendant steroid attached to the corona backbone is shown to self‐template the phase, providing a unique CoPhMoRE design strategy with high efficacy. The resulting sensors exhibit excellent stability and reversibility upon repeated analyte cycling. It is shown that molecular recognition using such constructs is viable even in vivo after sensor implantation into a murine model by employing a poly (ethylene glycol) diacrylate (PEGDA) hydrogel and porous cellulose interface to limit nonspecific absorption. The results demonstrate that CoPhMoRe templating is sufficiently robust to enable a new class of continuous, in vivo biosensors.
Effects of endothelin receptor blockade and COX inhibition on intestinal I/R injury in a rat model: Experimental research
Authors: Bercis Imge Ucar, Acelya Erikci, Kemal Kosemehmetoglu, Ceren Ozkul, Alper Bektas Iskit, Gulberk Ucar, Sezgin Zeren
Journal: International Journal of Surgery (2020)
Direct evidence for local IgE production in the human colonic mucosa
Authors: Karina Eva Canziani, Melisa Pucci Molineris, Luciana Guzman, Viviana Bernedo, Marcela García, Eugenia Margarita Altamirano, Cecilia Isabel Muglia, Guillermo Horacio Docena
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Lomustine is beneficial to older AML with ELN2017 adverse risk profile and intermediate karyotype: a FILO study
Authors: Laetitia Largeaud, Pascale Cornillet-Lefebvre, Jean-François Hamel, Pierre-Yves Dumas, Naïs Prade, Stéphanie Dufrechou, Julien Plenecassagnes, Isabelle Luquet, Odile Blanchet, Anne Banos, Marie C. Béné, Marc Bernard, Sarah Bertoli, Caroline Bonmati, Luc Matthieu Fornecker, Romain Guièze, Lamya Haddaoui, Mathilde Hunault, Jean Christophe Ianotto, Eric Jourdan, Mario Ojeda, Pierre Peterlin, Norbert Vey, Hacene Zerazhi, Hicheri Yosr, Ariane Mineur, Jean-Yves Cahn, Norbert Ifrah, Christian Récher, Arnaud Pigneux, Eric Delabesse, J.-P. Marolleau, A. Aleme, F. Orsini-Piocelle, N. Cadoux, N. Ifrah, M. Hunault, C. Marie, A. Al Jijakli, G. Lepeu, H. Zerazhi, M. Beyrne, A. Banos, S. Labarrere, E. Deconinck, M. Peria, A. El Yamani, O. Kadiri, B. Choufi, M. Brument, A. Pigneux, T. Leguay, P.-Y. Dumas, C. Berthou, G. Guillerm, G. Drugmanne, O. Tournilhac, G. Roy, B. Audhuy, S. Camara, D. Caillot, M. Grandjean, J.-Y. Cahn, C.-E. Bulabois, B. Fief, N. Vey, C. Ladraa, V. Dorvaux, M. Hagopian, N. Fegueux, C. Fenoll, V. Sabadash, M. Ojeda, C. Haby, F. Witz, C. Bonmati, M. Lhuire, J. Delaunay, P. Peterlin, L. Airiau, L. Mannone, I. Touitou, E. Jourdan, D. Umuhire, M. Alexis, O. Michel, F. Dreyfus, D. Bouscary, A. Cheung, L. Sanhes, F. Touhami, E. Ribas, M. Puyade, M.-P. Gallego-Hernanz, N. Hugon, C. Himberlin, L. Maggi, T. Lamy, A. Testu, E. Tavernier, S. Marchand, B. Lioure, C. Kravanja, L. Benboubker, D. Nollet, M. Attal, C. Recher, A. Sarry, A. Lhermitte, G. Yrica, D. Schwartz, N. Le Montagner, C. Fenoll, V. Sabadash, D. Nollet, L. Auvray, R. Delepine, A. Fayault
Journal: Leukemia (2020)
Healthy donor T cell responses to common cold coronaviruses and SARS-CoV-2
Authors: Bezawit A. Woldemeskel, Abena K. Kwaa, Caroline C. Garliss, Oliver Laeyendecker, Stuart C. Ray, Joel N. Blankson
Journal: Journal of Clinical Investigation (2020)

BACKGROUNDT cell responses to the common cold coronaviruses have not been well characterized. Preexisting T cell immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported, and a recent study suggested that this immunity was due to cross-recognition of the novel coronavirus by T cells specific for the common cold coronaviruses.METHODSWe used the enzyme-linked immunospot (ELISPOT) assay to characterize the T cell responses against peptide pools derived from the spike protein of 3 common cold coronaviruses (HCoV-229E, HCoV-NL63, and HCoV-OC43) and SARS-CoV-2 in 21 healthy donors (HDs) who were seronegative for SARS-CoV-2 and had no known exposure to the virus. An in vitro expansion culture assay was also used to analyze memory T cell responses.RESULTSWe found responses to the spike protein of the 3 common cold coronaviruses in many of the donors. We then focused on HCoV-NL63 and detected broad T cell responses to the spike protein and identified 22 targeted peptides. Interestingly, only 1 study participant had a significant response to SARS-CoV-2 spike or nucleocapsid protein in the ELISPOT assay. In vitro expansion studies suggested that T cells specific for the HCoV-NL63 spike protein in this individual could also recognize SARS-CoV-2 spike protein peptide pools.CONCLUSIONHDs have circulating T cells specific for the spike proteins of HCoV-NL63, HCoV-229E, and HCoV-OC43. T cell responses to SARS-CoV-2 spike and nucleocapsid proteins were present in only 1 participant and were potentially the result of cross-recognition by T cells specific for the common cold coronaviruses. Further studies are needed to determine whether this cross-recognition influences coronavirus disease 2019 (COVID-19) outcomes.
Highly Stretchable Metal–Polymer Conductor Electrode Array for Electrophysiology
Authors: Ruihua Dong, Xiaoyan Liu, Shiyu Cheng, Lixue Tang, Mian Chen, Leni Zhong, Zhen Chen, Shaoqin Liu, Xingyu Jiang
Journal: Advanced Healthcare Materials (2020)

Narrowing the mechanical mismatch between biological tissues (typically soft) and neural interfaces (hard) is essential for maintaining signal quality for the electrical recording of neural activity. However, only a few materials can satisfy all requirements for such electronics, which need to be both biocompatible and sufficiently soft. Here, a highly stretchable electrode array (SEA) is introduced, based on the liquid metal-polymer conductor (MPC), achieving high mechanical flexibility and good cytocompatability for neural interfaces. By utilizing the MPC, the SEA exhibits high stretchability (≈100%) and excellent cycling stability (>400 cycles). The cytocompatability of the SEA can allow for long-term culturing of primary neurons and enable signal recording of primary hippocampal neurons. In the future, the SEA could serve as a reliable and robust platform for diagnostics in neuronal tissues and greatly advance brain-machine interfaces.
Analysis of Drug Test Results Before and After the US Declaration of a National Emergency Concerning the COVID-19 Outbreak
Authors: Jacob J. Wainwright, Meriam Mikre, Penn Whitley, Eric Dawson, Angela Huskey, Andrew Lukowiak, Brett P. Giroir
Journal: JAMA (2020)

Taylor A. Ochalek, PhD; Kirk L. Cumpston, DO; Brandon K. Wills, DO; Tamas S. Gal, PhD; F. Gerard Moeller, MD