tbuckley/cabot-search huggingface dataset:
Deep Learning to Estimate RECIST in Patients with NSCLC Treated with PD-1 Blockade
Authors: Kathryn C. Arbour, Anh Tuan Luu, Jia Luo, Hira Rizvi, Andrew J. Plodkowski, Mustafa Sakhi, Kevin B. Huang, Subba R. Digumarthy, Michelle S. Ginsberg, Jeffrey Girshman, Mark G. Kris, Gregory J. Riely, Adam Yala, Justin F. Gainor, Regina Barzilay, Matthew D. Hellmann
Journal: Cancer Discovery (2020)

Abstract Real-world evidence (RWE), conclusions derived from analysis of patients not treated in clinical trials, is increasingly recognized as an opportunity for discovery, to reduce disparities, and to contribute to regulatory approval. Maximal value of RWE may be facilitated through machine-learning techniques to integrate and interrogate large and otherwise underutilized datasets. In cancer research, an ongoing challenge for RWE is the lack of reliable, reproducible, scalable assessment of treatment-specific outcomes. We hypothesized a deep-learning model could be trained to use radiology text reports to estimate gold-standard RECIST-defined outcomes. Using text reports from patients with non–small cell lung cancer treated with PD-1 blockade in a training cohort and two test cohorts, we developed a deep-learning model to accurately estimate best overall response and progression-free survival. Our model may be a tool to determine outcomes at scale, enabling analyses of large clinical databases. Significance: We developed and validated a deep-learning model trained on radiology text reports to estimate gold-standard objective response categories used in clinical trial assessments. This tool may facilitate analysis of large real-world oncology datasets using objective outcome metrics determined more reliably and at greater scale than currently possible. This article is highlighted in the In This Issue feature, p. 1
Is IL-6 the Right Target in COVID-19 Severe Pneumonia?
Authors: Mathieu Blot, Abderrahmane Bourredjem, Christine Binquet, Lionel Piroth, Mathieu Blot, Abderrahmane Bourredjem, Christine Binquet, Lionel Piroth, Jean-Pierre Quenot, Pierre-Emmanuel Charles, François Aptel, Sébastien Prin, Pascal Andreu, Marie Labruyère, Auguste Dargent, Maxime Nguyen, Belaid Bouhemad, Marjolaine Georges, Philippe Bonniaud, Guillaume Beltramo, Marielle Buisson, Bernard Bonnotte, Philip Bielefeld, Jeremy Barben, Alain Putot, Serge Monier, Audrey Large, Suzanne Mouries-Martin, Hervé Devilliers, Pascal Chavanet, Alexandre Guilhem
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Immune evasion in renal cell carcinoma: biology, clinical translation, future directions
Authors: Xiaoyang Wang, Robert Lopez, Rebecca A. Luchtel, Sassan Hafizi, Benjamin Gartrell, Niraj Shenoy
Journal: Kidney International (2020)

Targeted therapies and immune checkpoint inhibitors have advanced the treatment landscape of Renal Cell Carcinoma (RCC) over the last decade. While checkpoint inhibitors have demonstrated survival benefit and are currently approved in the front-line and second-line settings, primary and secondary resistance is common. A comprehensive understanding of the mechanisms of immune evasion in RCC is therefore critical to the development of effective combination treatment strategies. This article reviews the current understanding of the different, yet coordinated, mechanisms adopted by RCC cells to evade immune killing; summarizes various aspects of clinical translation thus far, including the currently registered RCC clinical trials exploring agents in combination with checkpoint inhibitors; and provides perspectives on the current landscape and future directions for the field.
EVs Containing Host Restriction Factor IFITM3 Inhibited ZIKV Infection of Fetuses in Pregnant Mice through Trans-placenta Delivery
Authors: Xue Zou, Meng Yuan, Tongyu Zhang, Nan Zheng, Zhiwei Wu
Journal: Molecular Therapy (2020)

Zika virus (ZIKV) infection can lead to neurological complications and fetal defects, and it has attracted global public health concerns. Effective treatment for ZIKV infection remains elusive, and a preventative vaccine is not yet available. Therapeutics for fetuses need to overcome placenta barriers to reach the fetuses and require higher safety standards. In the present study, we engineered mammalian extracellular vesicles (EVs) to deliver a host restriction factor, interferon-induced transmembrane protein 3 (IFITM3), for the treatment of ZIKV infection. Our results demonstrated that the IFITM3-containing EVs (IFITM3-Exos) suppressed ZIKV viremia by a 2-log reduction in pregnant mice. Moreover, the engineered EVs effectively delivered IFITM3 protein across the placental barrier and suppressed ZIKV in the fetuses with significant reduction of viremia in key fetal organs as measured by quantitative real-time PCR. Mechanistic study showed that IFITM3 was delivered to late endosomes/lysosomes where it inhibited viral entry into the host cells. Our study demonstrated that EVs could act as a cross-placenta drug delivery vehicle to the fetus, and IFITM3, an endogenous restriction factor, is a potential treatment for ZIKV infection during pregnancy. Zika virus (ZIKV) infection can lead to neurological complications and fetal defects, and it has attracted global public health concerns. Effective treatment for ZIKV infection remains elusive, and a preventative vaccine is not yet available. Therapeutics for fetuses need to overcome placenta barriers to reach the fetuses and require higher safety standards. In the present study, we engineered mammalian extracellular vesicles (EVs) to deliver a host restriction factor, interferon-induced transmembrane protein 3 (IFITM3), for the treatment of ZIKV infection. Our results demonstrated that the IFITM3-containing EVs (IFITM3-Exos) suppressed ZIKV viremia by a 2-log reduction in pregnant mice. Moreover, the engineered EVs effectively delivered IFITM3 protein across the placental barrier and suppressed ZIKV in the fetuses with significant reduction of viremia in key fetal organs as measured by quantitative real-time PCR. Mechanistic study showed that IFITM3 was delivered to late endosomes/lysosomes where it inhibited viral entry into the host cells. Our study demonstrated that EVs could act as a cross-placenta drug delivery vehicle to the fetus, and IFITM3, an endogenous restriction factor, is a potential treatment for ZIKV infection during pregnancy.
VEGFR2-targeted antibody fused with IFN mut regulates the tumor microenvironment of colorectal cancer and exhibits potent anti-tumor and anti-metastasis activity
Authors: Pengzhao Shang, Rui Gao, Yijia Zhu, Xiaorui Zhang, Yang Wang, Minji Guo, Hui Peng, Min Wang, Juan Zhang
Journal: Acta Pharmaceutica Sinica B (2020)

Although interferon α (IFNα) and anti-angiogenesis antibodies have shown appropriate clinical benefit in the treatment of malignant cancer, they are deficient in clinical applications. Previously, we described an anti-vascular endothelial growth factor receptor 2 (VEGFR2)-IFNα fusion protein named JZA01, which showed increased in vivo half-life and reduced side effects compared with IFNα, and it was more effective than the anti-VEGFR2 antibody against tumors. However, the affinity of the IFNα component of the fusion protein for its receptor-IFNAR1 was decreased. To address this problem, an IFNα-mutant fused with anti-VEGFR2 was designed to produce anti-VEGFR2-IFNαmut, which was used to target VEGFR2 with enhanced anti-tumor and anti-metastasis efficacy. Anti-VEGFR2-IFNαmut specifically inhibited proliferation of tumor cells and promoted apoptosis. In addition, anti-VEGFR2-IFNαmut inhibited migration of colorectal cancer cells and invasion by regulating the PI3K–AKT–GSK3β–snail signal pathway. Anti-VEGFR2-IFNαmut showed superior anti-tumor efficacy with improved tumor microenvironment (TME) by enhancing dendritic cell maturation, dendritic cell activity, and increasing tumor-infiltrating CD8+ T cells. Thus, this study provides a novel approach for the treatment of metastatic colorectal cancer, and this design may become a new approach to cancer immunotherapy.
Creation of an optic nerve sheath diameter ultrasound model for NeuroICU education
Authors: Heidi M. Felix, Kristin A. Rosenbush, Amy M. Lannen, Robert A. Pooley, Jason L. Siegel, Benjamin L. Brown, Melissa L. McMullan, Christina I. Collins, William D. Freeman
Journal: Military Medical Research (2020)

Abstract Background Using ultrasound to measure optic nerve sheath diameter (ONSD) is an emerging bedside technique to noninvasively assess intracranial pressure (ICP) in patients with brain injury. This technique is unique among bedside ultrasonography and is often performed by providers who have no formal ultrasound training. We sought to create a low-cost, 3D, reusable ONSD model to train neurology, neurosurgery, and critical care providers in measuring ICP. Results We identified 253 articles, of which 15 were associated with models and 2 with simulation. One gelatin model was reported, upon which we based our initial design. We could not validate the visual findings of this model; however, after constructing multiple beta models, the design most representative of human eye anatomy was a globe made of ballistics gel and either a 3 mm, 5 mm, or 7 mm × 50 mm 3D-printed optic nerve inserted into a platform composed of ballistics gel, all of which sat inside a 3D-printed skull. This model was used to teach ONSD measurements with ultrasound at a continuing medical education event prior to training on a live human model. Conclusion A simple 3D ballistic ONSD model allows learners to practice proper hand placement and pressure, basic landmarks, and ONSD measurement prior to operating on a human eye. This model is replicable and sustainable given that the globe and platform are composed of ballistics gel.
Comparison of nasal allergen challenges with dissolved Timothy grass pollen tablets and aqueous extract
Authors: Aarif O. Eifan, Alexandra Fedina, Stephen R. Durham, Guy W. Scadding
Journal: Allergy (2020)

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Private patient care in NHS hospitals: an opportunity for improved governance
Authors: Sarah C Walpole, May CI van Schalkwyk, Martin McKee
Journal: BMJ (2020)

The 2012 NHS reforms in England allowed trusts to generate more income from private practice in the expectation that this would support improved NHS care, but, as <b>Sarah Walpole and colleagues</b> show, existing governance arrangements provide no assurance that such benefits are being realised
Epidemiological and clinical characteristics of children with acute respiratory viral infections in the Philippines: a prospective cohort study
Authors: Yuki Furuse, Raita Tamaki, Akira Suzuki, Taro Kamigaki, Michiko Okamoto, Mariko Saito-Obata, Emiko Nakagawa, Mayuko Saito, Edelwisa Segubre-Mercado, Veronica Tallo, Socorro Lupisan, Hitoshi Oshitani
Journal: Clinical Microbiology and Infection (2020)

ObjectivesViral acute respiratory infection (ARI) remains a major global health problem, especially among children in low- and middle-income countries. The study was conducted to reveal aetiological significance of respiratory viruses among both non-hospitalized and hospitalized children.MethodsA cohort study of children with ARI at the household, primary healthcare facility, and hospital levels was conducted alongside a hospital-based study including non-cohort children from 2014 to 2016 in the Philippines. The ARI cases were recorded at households and healthcare facilities, and a clinical investigation was performed. Nasopharyngeal swabs were collected from the symptomatic children and tested for respiratory viruses via polymerase chain reaction. Then, the association between healthcare facility utilization and viral detection was investigated.ResultsOverall, 18,514 ARI cases were enrolled in the cohort study, and samples were collected from 4735 of these cases. The hospital-based study detected 648 ARI cases, all of which were sampled. Rhinovirus (22.2%; 1052/4735) was most frequently detected followed by respiratory syncytial virus (12.0%; 566/4735). Enterovirus (adjusted odds ratio, 1.8; 95% confidence interval, 1.1–2.8), human metapneumovirus (2.1, 1.4–3.2), rhinovirus (2.1, 1.8–2.6), and respiratory syncytial virus (1.6, 1.2–1.9) were significantly more prevalent in the ARI cases at healthcare facilities than in those in households. Of all ARI cases, 0.6% required hospitalization while 1.8% were hospitalized among the respiratory syncytial virus-positive cases (3.8, 3.0–4.9).ConclusionsWe determined the prevalence of respiratory viruses among children with ARIs at the household, primary healthcare facility, and hospital levels and the association with clinical characteristics. In particular, we discovered a significant disease burden and impact of respiratory syncytial virus infections as well as a considerable aetiological implication of rhinovirus infections.
Self‐care of heart failure patients: practical management recommendations from the Heart Failure Association of the European Society of Cardiology
Authors: Tiny Jaarsma, Loreena Hill, Antoni Bayes‐Genis, Hans‐Peter Brunner La Rocca, Teresa Castiello, Jelena Čelutkienė, Elena Marques‐Sule, Carla M. Plymen, Susan E. Piper, Barbara Riegel, Frans H. Rutten, Tuvia Ben Gal, Johann Bauersachs, Andrew J.S. Coats, Ovidiu Chioncel, Yuri Lopatin, Lars H. Lund, Mitja Lainscak, Brenda Moura, Wilfried Mullens, Massimo F. Piepoli, Giuseppe Rosano, Petar Seferovic, Anna Strömberg
Journal: European Journal of Heart Failure (2020)

Abstract Self‐care is essential in the long‐term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self‐care is related to medical and person‐centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self‐care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion.
Carvedilol induces biased β1 adrenergic receptor-nitric oxide synthase 3-cyclic guanylyl monophosphate signalling to promote cardiac contractility
Authors: Qingtong Wang, Ying Wang, Toni M West, Yongming Liu, Gopireddy R Reddy, Federica Barbagallo, Bing Xu, Qian Shi, Bingqing Deng, Wei Wei, Yang K Xiang
Journal: Cardiovascular Research (2020)

β-blockers are widely used in therapy for heart failure and hypertension. β-blockers are also known to evoke additional diversified pharmacological and physiological effects in patients. We aim to characterize the underlying molecular signalling and effects on cardiac inotropy induced by β-blockers in animal hearts.
What can we expect from first-generation COVID-19 vaccines?
Authors: Malik Peiris, Gabriel M Leung
Journal: The Lancet (2020)

A first generation of COVID-19 vaccines is expected to gain approval as soon as the end of 2020 or early 2021. A popular assumption is that these vaccines will provide population immunity that can reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and lead to a resumption of pre-COVID-19 "normalcy". Given an initial reproduction number of around 2·2,1 which has since been revised to as high as about 4, and taking into account overdispersion of infections,2 perhaps about 25–50% of the population would have to be immune to the virus to achieve suppression of community transmission.
Evaluation of the COVID-19 response in Spain: principles and requirements
Authors: Alberto L García-Basteiro, Helena Legido-Quigley, Carlos Álvarez-Dardet, Alex Arenas, Rafael Bengoa, Carme Borrell, Margarita Del Val, Manuel Franco, Montserrat Gea-Sánchez, Juan Gestal, Beatriz González López-Valcárcel, Ildefonso Hernández-Aguado, Joan C March, José Martín-Moreno, Clara Menéndez, Sergio Minué, Carles Muntaner, Miquel Porta, Daniel Prieto-Alhambra, Carme Vives Cases, Alberto L. Garcia-Basteiro, Helena Legido-Quigley
Journal: The Lancet Public Health (2020)
A large-scale genome–lipid association map guides lipid identification
Authors: Vanessa Linke, Katherine A. Overmyer, Ian J. Miller, Dain R. Brademan, Paul D. Hutchins, Edna A. Trujillo, Thiru R. Reddy, Jason D. Russell, Emily M. Cushing, Kathryn L. Schueler, Donald S. Stapleton, Mary E. Rabaglia, Mark P. Keller, Daniel M. Gatti, Gregory R. Keele, Duy Pham, Karl W. Broman, Gary A. Churchill, Alan D. Attie, Joshua J. Coon
Journal: Nature Metabolism (2020)
Recent Progress in the Design and Application of Supramolecular Peptide Hydrogels in Cancer Therapy
Authors: Ying Cai, Chao Zheng, Fengqin Xiong, Wei Ran, Yihui Zhai, Helen H. Zhu, Hao Wang, Yaping Li, Pengcheng Zhang
Journal: Advanced Healthcare Materials (2020)

Supramolecular peptide hydrogel (SPH) is a class of biomaterials self-assembled from peptide-based gelators through non-covalent interactions. Among many of its biomedical applications, the potential of SPH in cancer therapy has been vastly explored in the past decade, taking advantage of its good biocompatibility, multifunctionality, and injectability. SPHs can exert localized cancer therapy and induce systemic anticancer immunity to prevent tumor recurrence, depending on the design of SPH. This review first gives a brief introduction to SPH and then outlines the major types of peptide-based gelators that have been developed so far. The methodologies to tune the physicochemical properties and biological activities are summarized. The recent advances of SPH in cancer therapy as carriers, prodrugs, or drugs are highlighted. Finally, the clinical translation potential and main challenges in this field are also discussed.
Differential gene expression of tumor-infiltrating CD8<sup>+</sup>T cells in advanced versus early-stage colorectal cancer and identification of a gene signature of poor prognosis
Authors: Reem Saleh, Varun Sasidharan Nair, Salman M Toor, Rowaida Z Taha, Khaled Murshed, Mahmood Al-Dhaheri, Mahwish Khawar, Mahir Abdulla Petkar, Mohamed Abu Nada, Fares Al-Ejeh, Eyad Elkord
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Cytotoxic CD8 + T cell-mediated response is the most important arm of adaptive immunity, which dictates the capacity of the host immune response in eradicating tumor cells. Due to tumor intrinsic and/or extrinsic factors, the density and function of CD8 + tumor-infiltrating lymphocytes (TILs) could be compromised, leading to poor prognosis and survival. Methods Using RNA-Seq, transcriptomes of sorted CD3 + CD8 + TILs from treatment-naïve colorectal cancer (CRC) patients at advanced stages (III and IV) were compared with those from patients with early stages (I and II). A signature referred to as ‘poor prognosis CD8 gene signature (ppCD8sig)’ was identified and analyzed in The Cancer Genome Atlas CRC dataset. Scores for the ppCD8sig were calculated and classified as high, intermediate and low, and its prognostic significance was assessed using multivariate analysis and Cox proportional hazard model. Densities of CD3 + and CD8 + T cell infiltration in tumors from patients with high and low ppCD8sig scores were assessed by flow cytometry and immunostaining. Results Genes related to epigenetic regulation and response to hypoxia were upregulated in CD8 + TILs from patients with advanced stages, while genes related to T cell activation, cell proliferation and cell cycle were downregulated. Patients with high ppCD8sig score had poorer disease-specific survival (DSS) and shorter progression-free interval (PFI). The ppCD8sig was an independent prognostic indicator for DSS (HR 1.83, 95% CI 1.40 to 2.38, p&lt;0.0001) and PFI (HR 1.42, 95% CI 1.04 to 1.93, p=0.026). Additionally, patients with high ppCD8sig score were more likely to have advanced stages (χ 2 p&lt;0.0001) and residual disease after primary therapy (χ 2 p=0.046). Patients with high ppCD8sig score had reduced levels of CD3 + and CD8 + TILs and low Immunoscores (IS), compared to patients with low ppCD8sig score. Conclusions Our data provided insights into the altered regulation of biological mechanisms and signaling pathways in CD8 + TILs during CRC progression, and revealed a gene signature as an independent prognostic indicator. Patients with high ppCD8sig score had lower levels of TILs and low IS. These data further confirm the prognostic value of the identified ppCD8sig and potentially highlight its clinical relevance.
Surufatinib in advanced extrapancreatic neuroendocrine tumours (SANET-ep): a randomised, double-blind, placebo-controlled, phase 3 study
Authors: Jianming Xu, Lin Shen, Zhiwei Zhou, Jie Li, Chunmei Bai, Yihebali Chi, Zhiping Li, Nong Xu, Enxiao Li, Tianshu Liu, Yuxian Bai, Ying Yuan, Xingya Li, Xiuwen Wang, Jia Chen, Jieer Ying, Xianjun Yu, Shukui Qin, Xianglin Yuan, Tao Zhang, Yanhong Deng, Dianrong Xiu, Ying Cheng, Min Tao, Ru Jia, Wei Wang, Jing Li, Songhua Fan, Mengye Peng, Weiguo Su
Journal: The Lancet Oncology (2020)
Palbociclib and Trastuzumab in HER2-Positive Advanced Breast Cancer: Results from the Phase II SOLTI-1303 PATRICIA Trial
Authors: Eva Ciruelos, Patricia Villagrasa, Tomás Pascual, Mafalda Oliveira, Sonia Pernas, Laia Paré, Santiago Escrivá-de-Romaní, Luis Manso, Barbara Adamo, Eduardo Martínez, Javier Cortés, Silvia Vazquez, Antonia Perelló, Isabel Garau, Mireia Melé, Noelia Martínez, Alvaro Montaño, Begoña Bermejo, Serafin Morales, María J. Echarri, Estela Vega, Blanca González-Farré, Débora Martínez, Patricia Galván, Jordi Canes, Paolo Nuciforo, Xavier Gonzalez, Aleix Prat
Journal: Clinical Cancer Research (2020)

To assess palbociclib in combination with trastuzumab with or without endocrine therapy in patients with HER2-positive advanced breast cancer.PATRICIA is a prospective, open-label, multicenter phase II trial. Patients had received 2-4 prior lines of anti-HER2-based regimens. Treatment consisted of palbociclib 200 mg daily for 2 weeks and 1 week off plus trastuzumab. The study was based on a Simon two-stage design comprising three cohorts: estrogen receptor (ER)-negative (cohort A), ER-positive (cohort B1), and ER-positive with letrozole (cohort B2). ER-positive patients were randomized to cohorts B1 or B2. Primary endpoint was progression-free survival rate at 6 months (PFS6). Secondary objectives included safety and evaluation of the PAM50 intrinsic subtypes.Seventy-one patients were recruited (n = 15 in cohort A and 28 in each cohort B). The PFS6 rate in cohorts A, B1, and B2 was 33.3% (5/15), 42.8% (12/28), and 46.4% (13/28), respectively. Regarding safety, grade 1-2 and 3-4 toxicities occurred in 97.7% and 84.4% of patients, respectively. The most common grade 3-4 toxicities were neutropenia (66.4%) and thrombocytopenia (11.3%). Regarding PAM50, 59 (83.1%) tumors were profiled. Luminal disease defined by PAM50 was found independently associated with longer PFS compared with non-luminal disease (10.6 vs. 4.2 months median PFS; adjusted hazard ratio = 0.40; P = 0.003).Palbociclib in combination with trastuzumab is safe and exhibits promising survival outcomes in trastuzumab pretreated ER-positive/HER2-positive advanced breast cancer with a PAM50 Luminal A or B subtype. The enrollment was stopped prematurely, and a new randomized cohort was opened in this population.