tbuckley/cabot-search huggingface dataset:
AI-based analysis of CT images for rapid triage of COVID-19 patients
Authors: Qinmei Xu, Xianghao Zhan, Zhen Zhou, Yiheng Li, Peiyi Xie, Shu Zhang, Xiuli Li, Yizhou Yu, Changsheng Zhou, Longjiang Zhang, Olivier Gevaert, Guangming Lu
Journal: npj Digital Medicine (2021)

Abstract The COVID-19 pandemic overwhelms the medical resources in the stressed intensive care unit (ICU) capacity and the shortage of mechanical ventilation (MV). We performed CT-based analysis combined with electronic health records and clinical laboratory results on Cohort 1 ( n = 1662 from 17 hospitals) with prognostic estimation for the rapid stratification of PCR confirmed COVID-19 patients. These models, validated on Cohort 2 ( n = 700) and Cohort 3 ( n = 662) constructed from nine external hospitals, achieved satisfying performance for predicting ICU, MV, and death of COVID-19 patients (AUROC 0.916, 0.919, and 0.853), even on events happened two days later after admission (AUROC 0.919, 0.943, and 0.856). Both clinical and image features showed complementary roles in prediction and provided accurate estimates to the time of progression ( p &lt; 0.001). Our findings are valuable for optimizing the use of medical resources in the COVID-19 pandemic. The models are available here: https://github.com/terryli710/COVID_19_Rapid_Triage_Risk_Predictor .
Effect of climate change, connectivity, and socioeconomic factors on the expansion of the dengue virus transmission zone in 21st century Brazil: an ecological modelling study
Authors: Sophie A Lee, Theodoros Economou, Christovam Barcellos, Rafael Catão, Marilia Sá Carvalho, Rachel Lowe
Journal: The Lancet Planetary Health (2021)

BackgroundGlobally, incidence of dengue fever has increased more than 30-times in the past 50 years, with outbreaks becoming frequent in tropical and subtropical countries. This rapid emergence has been attributed to increased urbanisation, globalisation, international mobility, and climate change. Brazil is endemic to all four dengue virus serotypes with outbreaks occurring in every region of the country. Previous studies identified geographical barriers to dengue diffusion, with some regions of Brazil being relatively protected from outbreaks. These regions included areas in the south of the country where seasonal temperatures were too cold for vectors to efficiently transmit the virus, regions of the western Amazon that were isolated from infectious hosts and vectors, and mountainous regions of southeast Brazil.MethodsIn this ecological modelling study, we used a Bayesian spatiotemporal model to understand the effect of climate variation, connectivity between cities, and socioeconomic factors, such as urbanisation, on the expansion of the permanent dengue virus transmission zone in Brazil. We obtained monthly dengue fever case data from 5560 municipalities in Brazil for 2001–19 from the Notifiable Diseases Information System (SINAN) surveillance system. The model was fitted to an outbreak indicator defined as exceeding 300 cases per 100 000 inhabitants per year. Fixed effects included climate suitability and hydrometeorological variables obtained from the Climate Research Unit (University of East Anglia, Norwich, UK), the level of influence of a city from the Brazilian Regiōes de Influência das Cidades study, and socioeconomic factors, such as urbanisation, from census data. Spatiotemporal random effects were included to account for unobserved heterogeneity, spatial autocorrelation, and temporal trends.FindingsData from the past 10 years showed that pre-identified geographical barriers to dengue virus transmission are being eroded or destroyed completely. The emergence of dengue fever outbreaks in south Brazil coincided with an increase in the number of months per year with temperatures suitable for transmission.InterpretationUnderstanding the factors that lead to the erosion of barriers to dengue virus transmission will help identify regions at risk of future outbreaks, and improve public health preparedness to emerging and re-emerging diseases.FundingThe Royal Society.
SARS-CoV-2 spike therapeutic antibodies in the age of variants
Authors: Alina Baum, Christos A. Kyratsous
Journal: The Journal of Experimental Medicine (2021)

Christos Kyratsous, Vice President of Research, Infectious Diseases, and Viral Vector Technologies at Regeneron Pharmaceuticals, and Alina Baum, Associate Director, Infectious Diseases Associate at Regeneron Pharmaceuticals, discuss the development of antibody therapeutics targeting the spike protein of SARS-CoV-2.
From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution
Authors: Tran Thi Van Anh, Alilou Mostafa, Zhigang Rao, Simona Pace, Stefan Schwaiger, Christian Kretzer, Veronika Temml, Carsten Giesel, Paul M. Jordan, Rossella Bilancia, Christina Weinigel, Silke Rummler, Birgit Waltenberger, Tran Hung, Antonietta Rossi, Hermann Stuppner, Oliver Werz, Andreas Koeberle
Journal: Acta Pharmaceutica Sinica B (2021)

Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory reaction. Lipid mediators orchestrate both the initiation and resolution of inflammation. Switching from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as efficient strategy to relieve chronic inflammation, though drug candidates exhibiting such features are unknown. Starting from a library of Vietnamese medical plant extracts, we identified isomers of the biflavanoid 8-methylsocotrin-4′-ol from Dracaena cambodiana, which limit inflammation by targeting 5-lipoxygenase and switching the lipid mediator profile from leukotrienes to specialized pro-resolving mediators (SPM). Elucidation of the absolute configurations of 8-methylsocotrin-4′-ol revealed the 2S,γS-isomer being most active, and molecular docking studies suggest that the compound binds to an allosteric site between the 5-lipoxygenase subdomains. We identified additional subordinate targets within lipid mediator biosynthesis, including microsomal prostaglandin E2 synthase-1. Leukotriene production is efficiently suppressed in activated human neutrophils, macrophages, and blood, while the induction of SPM biosynthesis is restricted to M2 macrophages. The shift from leukotrienes to SPM was also evident in mouse peritonitis in vivo and accompanied by a substantial decrease in immune cell infiltration. In summary, we disclose a promising drug candidate that combines potent 5-lipoxygenase inhibition with the favorable reprogramming of lipid mediator profiles.
Activation of Sympathetic Signaling in Macrophages Blocks Systemic Inflammation and Protects against Renal Ischemia-Reperfusion Injury
Authors: Sho Hasegawa, Tsuyoshi Inoue, Yasuna Nakamura, Daichi Fukaya, Rie Uni, Chia-Hsien Wu, Rie Fujii, Wachirasek Peerapanyasut, Akashi Taguchi, Takahide Kohro, Shintaro Yamada, Mikako Katagiri, Toshiyuki Ko, Seitaro Nomura, Atsuko Nakanishi Ozeki, Etsuo A. Susaki, Hiroki R. Ueda, Nobuyoshi Akimitsu, Youichiro Wada, Issei Komuro, Masaomi Nangaku, Reiko Inagi
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement The detailed role of neural activity in inflammatory diseases is still unclear because it varies according to the disease situation and responsible cell types. This study shows that activation of β 2-adrenergic receptor (Adrb2) signaling in macrophages induces the expression of T cell Ig and mucin domain 3 ( Tim3 ), which contributes to anti-inflammatory phenotypic alterations. Experiments using conditional knockout mice reveal that macrophage Adrb2 signaling directly mitigates LPS-induced systemic inflammation and renal ischemia-reperfusion injury (IRI). The adoptive transfer of Adrb2 signal–activated macrophages also protects against renal IRI, in association with the accumulation of Tim3 -expressing macrophages in the renal tissue. These results indicate that macrophage Adrb2 signaling plays critical roles in the severity of AKI. Background The sympathetic nervous system regulates immune cell dynamics. However, the detailed role of sympathetic signaling in inflammatory diseases is still unclear because it varies according to the disease situation and responsible cell types. This study focused on identifying the functions of sympathetic signaling in macrophages in LPS-induced sepsis and renal ischemia-reperfusion injury (IRI). Methods We performed RNA sequencing of mouse macrophage cell lines to identify the critical gene that mediates the anti-inflammatory effect of β 2-adrenergic receptor (Adrb2) signaling. We also examined the effects of salbutamol (a selective Adrb2 agonist) in LPS-induced systemic inflammation and renal IRI. Macrophage-specific Adrb2 conditional knockout (cKO) mice and the adoptive transfer of salbutamol-treated macrophages were used to assess the involvement of macrophage Adrb2 signaling. Results In vitro , activation of Adrb2 signaling in macrophages induced the expression of T cell Ig and mucin domain 3 ( Tim3 ), which contributes to anti-inflammatory phenotypic alterations. In vivo , salbutamol administration blocked LPS-induced systemic inflammation and protected against renal IRI; this protection was mitigated in macrophage-specific Adrb2 cKO mice. The adoptive transfer of salbutamol-treated macrophages also protected against renal IRI. Single-cell RNA sequencing revealed that this protection was associated with the accumulation of Tim3 -expressing macrophages in the renal tissue. Conclusions The activation of Adrb2 signaling in macrophages induces anti-inflammatory phenotypic alterations partially via the induction of Tim3 expression, which blocks LPS-induced systemic inflammation and protects against renal IRI.
Efficacy and Safety of First-Line Immunotherapy Combinations for Advanced NSCLC: A Systematic Review and Network Meta-Analysis
Authors: Lihui Liu, Hua Bai, Chao Wang, Samuel Seery, Zhijie Wang, Jianchun Duan, Sini Li, Pei Xue, Guoqiang Wang, Yiting Sun, Xinyang Du, Xue Zhang, Zixiao Ma, Jie Wang
Journal: Journal of Thoracic Oncology (2021)
Abstract PO-009: Targeting a unique electrochemical vulnerability in a pediatric brain tumor to potentiate proton beam radiotherapy
Authors: Daniel Pomeranz Krummel, Laura Kallay, Debanjan Bhattacharya, Vaibhavkumar Gawali, Kamdem T. Donatien, Taukir Ahmed, James M. Cook, Michael Lamba, Susanne Wells, Ralph E. Vatner, Mathieu Sertorio, Dan T. Ionascu, Soma Sengupta
Journal: Clinical Cancer Research (2021)

Abstract Medulloblastoma (MB) is the most common malignant (WHO Grade IV) primary brain cancer in children, adolescents, and young adults. Radiotherapy (RT) is a mainstay of MB treatment, as it is for most childhood and adult cancers. RT dose and frequency needed to achieve efficacy in MB patients severely impacts survival outcomes and is the cause of long-term cognitive deficits. To improve on short-term side effects and long-term complications, scanning beam proton therapy is employed, when available. While this recent technological advance significantly reduces damage to surrounding healthy brain tissue, survivors continue to experience induced radiation damage, including neurocognitive sequelae. To impact survivors’ health-related quality of life and caregivers’ emotional and financial burden, it is critical to identify approaches that reduce RT dose to mitigate side-effects without impacting RT effectiveness. We are investigating targeting a unique MB electrochemical vulnerability as a means to sensitize MB tumor cells to RT. There are four MB molecular subgroups: wingless, sonic-hedgehog, Group 3, and Group 4. Our analysis of 763 MB tumor transcriptomes reveals that all Group 3 MB tumors share an enhanced expression of genes-coding for subunits of the Type-A GABA receptor (GABAAR), a chloride channel. Using patch-clamp electrophysiology, we found that GABAARs conduct Cl− in MB cells and that a brain-penetrant benzodiazepine (BZ) enhances this effect and triggers cytotoxic responses commensurate with mitochondrial depolarization. We find that BZ combined with RT, even at a sub-lethal dose, is highly effective in impairing the viability of MB tumor cells, greater than RT alone. Our BZis capable of penetrating the blood-brain barrier in minutes, is metabolically stable, and showed no toxicity in a primate model. We are investigating its suitability to be used concomitant with proton beam radiotherapy, replacing standard of care vincristine, to reduce radiation-induced brain toxicity experienced by MB patients and survivors while not decreasing RT effectiveness. Citation Format: Daniel Pomeranz Krummel, Laura Kallay, Debanjan Bhattacharya, Vaibhavkumar Gawali, Kamdem T. Donatien, Taukir Ahmed, James M. Cook, Michael Lamba, Susanne Wells, Ralph E. Vatner, Mathieu Sertorio, Dan T. Ionascu, Soma Sengupta. Targeting a unique electrochemical vulnerability in a pediatric brain tumor to potentiate proton beam radiotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-009.
Inhibition of TGF-β with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression
Authors: Swati Biswas, Marta Guix, Cammie Rinehart, Teresa C. Dugger, Anna Chytil, Harold L. Moses, Michael L. Freeman, Carlos L. Arteaga
Journal: Journal of Clinical Investigation (2017)

The authors recently became aware of errors in the assembly of Figure 3A that resulted in incorrect images for the U6 Northern blot for the lung cancer and breast cancer cell lines.
Incidence and Outcomes of Pneumonia in Patients With Heart Failure
Authors: Li Shen, Pardeep S. Jhund, Inder S. Anand, Ankeet S. Bhatt, Akshay S. Desai, Aldo P. Maggioni, Felipe A. Martinez, Marc A. Pfeffer, Adel R. Rizkala, Jean L. Rouleau, Karl Swedberg, Muthiah Vaduganathan, Orly Vardeny, Dirk J. van Veldhuisen, Faiez Zannad, Michael R. Zile, Milton Packer, Scott D. Solomon, John J.V. McMurray
Journal: Journal of the American College of Cardiology (2021)

The incidence of pneumonia and subsequent outcomes has not been compared in patients with heart failure and reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). This study aimed to examine the rate and impact of pneumonia in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) and PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in Heart Failure with Preserved Ejection Fraction) trials. The authors analyzed the incidence of investigator-reported pneumonia and the rates of HF hospitalization, cardiovascular death, and all-cause death before and after the occurrence of pneumonia, and estimated risk after the first occurrence of pneumonia in unadjusted and adjusted analyses (the latter including N-terminal pro–B-type natriuretic peptide). In PARADIGM-HF, 528 patients (6.3%) developed pneumonia after randomization, giving an incidence rate of 29 (95% CI: 27 to 32) per 1,000 patient-years. In PARAGON-HF, 510 patients (10.6%) developed pneumonia, giving an incidence rate of 39 (95% CI: 36 to 42) per 1,000 patient-years. The subsequent risk of all trial outcomes was elevated after the occurrence of pneumonia. In PARADIGM-HF, the adjusted hazard ratio (HR) for the risk of death from any cause was 4.34 (95% CI: 3.73 to 5.05). The corresponding adjusted HR in PARAGON-HF was 3.76 (95% CI: 3.09 to 4.58). The incidence of pneumonia was high in patients with HF, especially HFpEF, at around 3 times the expected rate. A first episode of pneumonia was associated with 4-fold higher mortality. (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF], NCT01035255; Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] With ARB [Angiotensin Receptor Blocker] Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF], NCT01920711)
Cotton pan-genome retrieves the lost sequences and genes during domestication and selection
Authors: Jianying Li, Daojun Yuan, Pengcheng Wang, Qiongqiong Wang, Mengling Sun, Zhenping Liu, Huan Si, Zhongping Xu, Yizan Ma, Boyang Zhang, Liuling Pei, Lili Tu, Longfu Zhu, Ling-Ling Chen, Keith Lindsey, Xianlong Zhang, Shuangxia Jin, Maojun Wang
Journal: Genome biology (2021)

Abstract Background Millennia of directional human selection has reshaped the genomic architecture of cultivated cotton relative to wild counterparts, but we have limited understanding of the selective retention and fractionation of genomic components. Results We construct a comprehensive genomic variome based on 1961 cottons and identify 456 Mb and 357 Mb of sequence with domestication and improvement selection signals and 162 loci, 84 of which are novel, including 47 loci associated with 16 agronomic traits. Using pan-genome analyses, we identify 32,569 and 8851 non-reference genes lost from Gossypium hirsutum and Gossypium barbadense reference genomes respectively, of which 38.2% (39,278) and 14.2% (11,359) of genes exhibit presence/absence variation (PAV). We document the landscape of PAV selection accompanied by asymmetric gene gain and loss and identify 124 PAVs linked to favorable fiber quality and yield loci. Conclusions This variation repertoire points to genomic divergence during cotton domestication and improvement, which informs the characterization of favorable gene alleles for improved breeding practice using a pan-genome-based approach.
SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 <sup>+</sup> T cell activation in COVID-19 patients
Authors: Sunil Kumar Saini, Ditte Stampe Hersby, Tripti Tamhane, Helle Rus Povlsen, Susana Patricia Amaya Hernandez, Morten Nielsen, Anne Ortved Gang, Sine Reker Hadrup
Journal: Science Immunology (2021)

T cells are important for effective viral clearance, elimination of virus-infected cells and long-term disease protection. To examine the full-spectrum of CD8
2013 ACCF/AHA Key Data Elements and Definitions for Measuring the Clinical Management and Outcomes of Patients With Acute Coronary Syndromes and Coronary Artery Disease
Authors: Christopher P. Cannon, Ralph G. Brindis, Bernard R. Chaitman, David J. Cohen, J. Thomas Cross, Joseph P. Drozda, Francis M. Fesmire, Dan J. Fintel, Gregg C. Fonarow, Keith A. Fox, Darryl T. Gray, Robert A. Harrington, Karen A. Hicks, Judd E. Hollander, Harlan Krumholz, Darwin R. Labarthe, Janet B. Long, Alice M. Mascette, Connie Meyer, Eric D. Peterson, Martha J. Radford, Matthew T. Roe, James B. Richmann, Harry P. Selker, David M. Shahian, Richard E. Shaw, Sharon Sprenger, Robert Swor, James A. Underberg, Frans Van de Werf, Bonnie H. Weiner, William S. Weintraub
Journal: Circulation (2013)
Audio Interview: Covid-19 Vaccines and Pregnancy — A Conversation with CDC Director Rochelle Walensky
Authors: Eric J. Rubin, Lindsey R. Baden, Rochelle P. Walensky, Stephen Morrissey
Journal: New England Journal of Medicine (2021)

Covid-19 Vaccines and Pregnancy — A Conversation with CDC Director Rochelle Walensky In this audio interview conducted on April 16, 2021, the editors are joined by CDC director and infectious disea...
Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial
Authors: Andrew Bottomley, Corneel Coens, Justyna Mierzynska, Christian U Blank, Mario Mandalà, Georgina V Long, Victoria G Atkinson, Stéphane Dalle, Andrew M Haydon, Andrey Meshcheryakov, Adnan Khattak, Matteo S Carlino, Shahneen Sandhu, Susana Puig, Paolo A Ascierto, James Larkin, Paul C Lorigan, Piotr Rutkowski, Dirk Schadendorf, Rutger Koornstra, Leonel Hernandez-Aya, Anna Maria Di Giacomo, Alfonsus J M van den Eertwegh, Jean-Jacques Grob, Ralf Gutzmer, Rahima Jamal, Alexander C J van Akkooi, Clemens Krepler, Nageatte Ibrahim, Sandrine Marreaud, Michal Kicinski, Stefan Suciu, Caroline Robert, Alexander M M Eggermont, Thierry Lesimple, Michele Maio, Gerald Linette, Laurent Mortier, Inge Marie Svane, Jacob Schachter, Michael Brown, Peter Hersey, Catherine Barrow, Ragini Kudchadkar, Caroline Dutriaux, Xinni Song, Pietro Quaglino, Paola Queirolo, Friedegund Meier, Daniil Stroyakovskiy, Bernard Guillot, Pablo Luis Ortiz Romero, Lars Bastholt, Claus Garbe, Florent Grange, Peter Mohr, Alain Algazi, Oliver Bechter, Micaela Hernberg, Carmen Loquai, Frank Meiss, Vanna Chiarion Sileni, Gil Bar-Sela, Bernard Fitzharris, Philippe Saiag, Jean-Philippe Arnault, Jan-Christoph Simon, Rosalie Stephens, Jean-Francois Baurain, Célèste Lebbe, Patrick Combemale, Reinhard Dummer, Axel Hauschild, Phillip Parente, Naoya Yamazaki, Mohammed Milhem, Marie-Thérèse Leccia, Lionel Geoffrois, Lutz Kretschmer, Elaine Dunwoodie, John Walker, Michal Lotem, Daniel Hendler, Andrzej Mackiewicz, Lidija Sekulovic, Marcin Dzienis, Geke A.P. Hospers, Marco Siano, Jessica Hassel, Philippa Corrie, Maria-Jose Passos, Max Levin, Christoph Hoeller, Laurent Machet, Sigrun Hallmeyer, Ashita Waterston, Vincent Descamps, Felix Kiecker, Maureen Aarts, Henrik Schmidt, Ana Raimundo, Marta Nyakas, Jean-Philippe Lacour, Carola Berking, Pier Francesco Ferrucci, Michael Jameson, Kevin Kim, Kenji Yokota, Joseph Kerger, François Aubin, Gerard Groenewegen, Helena Kapiteijn, Wolf-Henning Boehncke, Jochen Utikal, Richard Casasola, Ernest Marshall, Virginia Ferraresi, Erika Richtig, Suzana Matkovic, Takashi Inozume, Timothy Crook, Catriona McNeil, Yoshio Kiyohara, Marie-Francoise Avril, Rüdiger Hein, Patrick Terheyden, Paul Nathan, Jun Aoi, Tanja Skytta, Thomas Jouary, Tatsuya Takenouchi, Oddbjorn Straume, César Martins, Guzel Mukhametshina
Journal: The Lancet Oncology (2021)