tbuckley/cabot-search huggingface dataset:
Abstract IA04: COVID-19 in patients with lung cancers in New York City
Authors: Jia Luo, Hira Rizvi, Isabel R. Preeshagul, Jacklynn V. Egger, David Hoyos, Chaitanya Bandlamudi, Mark T.A. Donoghue, Marta Łuksza, Benjamin D. Greenbaum, Jedd D. Wolchok, Mark G. Kris, Matthew D. Hellmann
Journal: Clinical Cancer Research (2020)

Abstract Background: Patients with lung cancers may have distinct vulnerability to severe COVID-19. Understanding the patient-specific and cancer-specific features that impact severity of COVID-19 may inform optimal cancer care during this pandemic. A key question is whether PD-1 blockade therapy impacts COVID-19 severity. Methods: We identified consecutive patients with lung cancer and a positive SARS-CoV-2 RT-PCR test seen at a single cancer center in New York City. We performed detailed manual review of the disease course, medical and oncologic history. COVID-19 severity outcomes were predefined, including need for hospitalization, ICU/intubation/transition to DNI-status, or death. We examined clinical features associated with severity using single and multivariable analyses. Regarding the impact of PD-1 blockade, we prespecified several bio-plausible comparisons of PD-1 exposure. HLA alleles were inferred from NGS and compared to controls with lung cancer and no known COVID-19. Results: We identified 102 patients with lung cancers and a SARS-CoV-2 positive swab between March 12, 2020 and May 6, 2020. Patients were followed until May 11, 2020. COVID-19 was severe in patients with lung cancers (62% hospitalized, 25% died), but accounted for only 11% of deaths among patients with lung cancer during the pandemic. Determinants of COVID-19 severity were largely patient specific, including smoking status and chronic obstructive pulmonary disease. Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies, did not impact severity. Likelihood of severe COVID-19 was generally similar across HLA class I supertypes. We found no significant differences in the impact of PD-1 blockade on COVID-19 severity. Modest numerical increases in severity of COVID-19 associated with prior PD-1 blockade were diminished (Odds ratio 0.86-1.01) after adjusting for expected imbalances in prior smoking history. Most patients recovered from COVID-19, including 25% of patients initially requiring intubation. Conclusion: COVID-19 is associated with a high burden of severity in patients with lung cancers. Patient-specific features, rather than cancer-specific features or treatments, were the greatest determinants of severity. In particular, PD-1 blockade did not appear to impact severity of COVID-19 in patients with lung cancers. Citation Format: Jia Luo, Hira Rizvi, Isabel R. Preeshagul, Jacklynn V. Egger, David Hoyos, Chaitanya Bandlamudi, Mark T.A. Donoghue, Marta Łuksza, Benjamin D. Greenbaum, Jedd D. Wolchok, Mark G. Kris, Matthew D. Hellmann. COVID-19 in patients with lung cancers in New York City [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 IA04.
Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19
Authors: Elizabeth R. Mann, Madhvi Menon, Sean Blandin Knight, Joanne E. Konkel, Christopher Jagger, Tovah N. Shaw, Siddharth Krishnan, Magnus Rattray, Andrew Ustianowski, Nawar Diar Bakerly, Paul Dark, Graham M. Lord, Angela Simpson, Timothy Felton, Ling-Pei Ho, Marc Feldmann, John R. Grainger, Tracy Hussell
Journal: Science Immunology (2020)

COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1 and IP-10, and most strikingly, modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of COVID-19 patients and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission suggesting immune-modulating therapies would be most beneficial at early timepoints.
Covid-19: Waiting times in England reach record highs
Authors: Shaun Griffin
Journal: BMJ (2020)

Waiting times in England reach record highs Shaun GriffinMore than 83 000 patients in England waited more than a year for NHS treatment in July, the highest number since October 2008 and an 81-fold increase from 1032 in July last year, latest figures have shown. 1 The number of people who had been on waiting lists for more than 18 weeks in July was also the highest since records began in 2007, at 2.15 million.Just 46.8% of patients were treated within 18 weeks in July, against the 92% target-the lowest since records began, data from NHS England showed.The average wait for treatment by a hospital consultant rose to 19.6 weeks in July 2020.
Enrichment Benefits of Risk Algorithms for Pulmonary Arterial Hypertension Clinical Trials
Authors: Jacqueline V. Scott, Christine E. Garnett, Manreet K. Kanwar, Norman L. Stockbridge, Raymond L. Benza
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Event-driven primary endpoints are increasingly used in pulmonary arterial hypertension clinical trials, substantially increasing required sample sizes and trial lengths. The U.S. Food and Drug Administration advocates the use of prognostic enrichment of clinical trials by preselecting a patient population with increased likelihood of experiencing the trial's primary endpoint.Objectives: This study compares validated clinical scales of risk (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, the French score, and Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management [REVEAL] 2.0) to identify patients who are likely to experience a clinical worsening event for trial enrichment.Methods: Baseline data from three pulmonary arterial hypertension clinical trials (AMBITION [a Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects with Pulmonary Arterial Hypertension], SERAPHIN [Study of Macitentan on Morbidity and Mortality in Patients with Symptomatic Pulmonary Arterial Hypertension], and GRIPHON [Selexipag in Pulmonary Arterial Hypertension]) were pooled and standardized. Receiver operating curves were used to measure each algorithm's performance in predicting clinical worsening within the pooled placebo cohort. Power simulations were conducted to determine sample size and treatment time reductions for multiple enrichment strategies. A cost analysis was performed to illustrate potential financial savings by applying enrichment to GRIPHON.Measurements and Main Results: All risk algorithms were compared using area under the receiver operating curve and substantially outperformed prediction per New York Heart Association Functional Class. The REVEAL 2.0's risk grouping provided the greatest time and sample size savings in AMBITION and GRIPHON for all enrichment strategies but lacked appropriate inputs (i.e., N-terminal-proB-type natriuretic peptide) to perform as well in SERAPHIN. Cost analysis applied to GRIPHON demonstrated the greatest financial benefit by enrolling patients with a REVEAL score ≥8.Conclusions: This preliminary study demonstrates the feasibility of risk algorithms for pulmonary arterial hypertension trial enrichment and a need for further investigation.
Isolated Metastasis to Spleen-Stomach Space From Follicular Thyroid Cancer Combined With a Benign Subcutaneous Nodule on 18F-FDG PET/CT and 131I Scintigraphy
Authors: Xiuyu Guo, Hua He, Qiaolin Gao, Yinhua Jin
Journal: Clinical Nuclear Medicine (2020)

A 40-year-old woman with follicular thyroid cancer underwent a systemic PET/CT evaluation before operation and then received total thyroidectomy and radioactive 131I ablation therapy. Posttreatment imaging of 131I whole-body scan with SPECT/CT showed that metastasis on the spleen-stomach space coexists with mimicking subcutaneous metastasis, considering their level of 131I accumulation and morphological changes on PET/CT. However, histopathology confirmed the subcutaneous lesion of fibrous hyperplasia by fine-needle aspiration. This case demonstrates a vital role of SPECT/CT in the diagnosis of metastatic thyroid cancer and mimicking metastasis.
Tumor microenvironment conditions that favor vessel co-option in colorectal cancer liver metastases: A theoretical model
Authors: Miran Rada, Anthoula Lazaris, Audrey Kapelanski-Lamoureux, Thomas Z Mayer, Peter Metrakos
Journal: Seminars in Cancer Biology (2020)

Vessel co-option is an alternative strategy by which tumour cells vascularize and gain access to nutrients to support tumour growth, survival and metastasis. In vessel co-option, the cancer cells move towards the pre-existing vasculature and hijack them. Vessel co-option is adopted by a wide range of human tumours including colorectal cancer liver metastases (CRCLM) and is responsible for the effectiveness of treatment in CRCLM. Furthermore, vessel co-option is an intrinsic feature and an acquired mechanism of resistance to anti-angiogenic treatment. In this review, we describe the microenvironment, the molecular players, discovered thus far of co-opting CRCLM lesions and propose a theoretical model. We also highlight key unanswered questions that are critical to improving our understanding of CRCLM vessel co-option and for the development of effective approaches for the treatment of co-opting tumours.
A single-domain bispecific antibody targeting CD1d and the NKT T-cell receptor induces a potent antitumor response
Authors: Roeland Lameris, Adam Shahine, Daniel G. Pellicci, Adam P. Uldrich, Stephanie Gras, Jérôme Le Nours, Richard W. J. Groen, Jana Vree, Scott J. J. Reddiex, Sergio M. Quiñones-Parra, Stewart K. Richardson, Amy R. Howell, Sonja Zweegman, Dale I. Godfrey, Tanja D. de Gruijl, Jamie Rossjohn, Hans J. van der Vliet
Journal: Nature Cancer (2020)
<i>June Medical Services v. Russo</i> — A Threat to Physicians’ Standing to Challenge Abortion Regulations
Authors: Joanne D. Rosen
Journal: New England Journal of Medicine (2020)

In June Medical Services v. Russo, the Supreme Court rejected Louisiana's request to revisit long-established precedent and deny the legal entitlement of physicians to bring suit to challenge abortion laws. But several justices urged that this entitlement be reexamined.
Olanzapine for Prevention of Vomiting in Children and Adolescents Receiving Highly Emetogenic Chemotherapy: Investigator-Initiated, Randomized, Open-Label Trial
Authors: Ramavath D. Naik, Sreenivas V, Vishwajeet Singh, Ashwati S. Pillai, Deepa Dhawan, Sameer Bakhshi
Journal: Journal of Clinical Oncology (2020)

Chemotherapy-induced nausea and vomiting (CINV) is a significant toxicity of chemotherapy. Olanzapine is recommended in adult patients for the prevention of CINV but has not been prospectively investigated in children.This investigator-initiated, randomized, open-label trial evaluated olanzapine in children (ages 5-18 years) scheduled to receive the first cycle of highly emetogenic chemotherapy (HEC). All participants received aprepitant, ondansetron, and dexamethasone during and 2 days after chemotherapy. Participants in the study group additionally received oral olanzapine 0.14 mg/kg/day (rounded to the nearest 2.5 mg; maximum, 10 mg) during the chemotherapy block and 3 days postchemotherapy. The primary objective was to compare complete response (CR) rates (no vomiting and no rescue medication) between the groups in the acute, delayed, and overall periods. Nausea comparison and safety evaluation were secondary and additional objectives, respectively. The collection of outcomes and adverse events was performed daily until the completion of the overall period.A total of 240 patients underwent randomization. We performed a modified intention-to-treat analysis on 231 patients (116 in the control group and 115 in the study group). A higher proportion of patients in the olanzapine group achieved CR in the acute period (78% v 59%; P = .001), delayed period (74% v 47%; P < .001) and overall period (64% v 38%; P < .001) than in the control group. The proportion of patients with no nausea was significantly higher in the olanzapine group in the acute period (74% v 52%; P < .001), delayed period (74% v 47%; P < .001), and overall period (64% v 37%; P < .001). Grade 1/2 somnolence was greater in the olanzapine group (35% v 11%; P < .001). There was no grade 3/4 somnolence reported.Olanzapine significantly improved CR rates for vomiting in children receiving the first cycle of HEC.
Time to reality check the promises of machine learning-powered precision medicine
Authors: Jack Wilkinson, Kellyn F Arnold, Eleanor J Murray, Maarten van Smeden, Kareem Carr, Rachel Sippy, Marc de Kamps, Andrew Beam, Stefan Konigorski, Christoph Lippert, Mark S Gilthorpe, Peter W G Tennant
Journal: The Lancet Digital Health (2020)

Machine learning methods, combined with large electronic health databases, could enable a personalised approach to medicine through improved diagnosis and prediction of individual responses to therapies. If successful, this strategy would represent a revolution in clinical research and practice. However, although the vision of individually tailored medicine is alluring, there is a need to distinguish genuine potential from hype. We argue that the goal of personalised medical care faces serious challenges, many of which cannot be addressed through algorithmic complexity, and call for collaboration between traditional methodologists and experts in medical machine learning to avoid extensive research waste.
Reflections on Our Inaugural Year of JACC: CardioOncology, With Gratitude and Tireless Devotion
Authors: Bonnie Ky, MD, MSCE
Journal: JACC CardioOncology (2020)

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One year ago, we launched the first issue of JACC: CardioOncology, wherein I outlined my vision for this journal: to become the essential resource for the field of cardio-oncology; to play a vital and transformative role in advancing the field and care of our patients by
Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study
Authors: Emma Jones, Holger Hummerich, Emmanuelle Viré, James Uphill, Athanasios Dimitriadis, Helen Speedy, Tracy Campbell, Penny Norsworthy, Liam Quinn, Jerome Whitfield, Jacqueline Linehan, Zane Jaunmuktane, Sebastian Brandner, Parmjit Jat, Akin Nihat, Tze How Mok, Parvin Ahmed, Steven Collins, Christiane Stehmann, Shannon Sarros, Gabor G Kovacs, Michael D Geschwind, Aili Golubjatnikov, Karl Frontzek, Herbert Budka, Adriano Aguzzi, Hata Karamujić-Čomić, Sven J van der Lee, Carla A Ibrahim-Verbaas, Cornelia M van Duijn, Beata Sikorska, Ewa Golanska, Pawel P Liberski, Miguel Calero, Olga Calero, Pascual Sanchez-Juan, Antonio Salas, Federico Martinón-Torres, Elodie Bouaziz-Amar, Stéphane Haïk, Jean-Louis Laplanche, Jean-Phillipe Brandel, Phillipe Amouyel, Jean-Charles Lambert, Piero Parchi, Anna Bartoletti-Stella, Sabina Capellari, Anna Poleggi, Anna Ladogana, Maurizio Pocchiari, Serena Aneli, Giuseppe Matullo, Richard Knight, Saima Zafar, Inga Zerr, Stephanie Booth, Michael B Coulthart, Gerard H Jansen, Katie Glisic, Janis Blevins, Pierluigi Gambetti, Jiri Safar, Brian Appleby, John Collinge, Simon Mead
Journal: The Lancet Neurology (2020)
Tracing faded rainbows
Authors: Debbie Challis
Journal: The Lancet Psychiatry (2020)

At the beginning of the novel Mrs Dalloway, Virginia Woolf describes Clarissa Dalloway stepping out on a beautiful June day, revelling in the noise and bustle of London streets. I re-read Woolf's novel in April, tracing Clarissa's steps as she walked to Bond Street and shopped for flowers. I felt nostalgic for the street life so vividly depicted. While I was virtually walking through the London of Woolf's impressionistic prose, news bulletins flashed up images of empty streets and roads deadened by the lockdown.
Letter to the editor: COVID-19 cases among school-aged children and school-based measures in Hong Kong, July 2020
Authors: MW Fong, BJ Cowling, GM Leung, P Wu
Journal: Eurosurveillance (2020)

Preview this article: Letter to the editor: COVID-19 cases among school-aged children and school-based measures in Hong Kong, July 2020, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/25/37/eurosurv-25-37-4-1.gif
Selective potassium uptake via biocompatible zeolite–polymer hybrid microbeads as promising binders for hyperkalemia
Authors: Zhoujun Wang, Wei Sun, Zhiwei Wei, Jianxu Bao, Xin Song, Yupei Li, Haifeng Ji, Jue Zhang, Chao He, Baihai Su, Weifeng Zhao, Changsheng Zhao
Journal: Bioactive Materials (2020)

Patients with chronic kidney disease are at high risk of hyperkalemia that is associated with various life-threatening complications. Treatments primarily rely on orally administered potassium binding agents, along with low curative effects and various side effects. Herein, direct serum potassium uptake was realized via zeolite-heparin-mimicking-polymer hybrid microbeads. The preparation process involved the synthesis of the heparin-mimicking polymer via the in situ cross-linking polymerization of acrylic acid and N-vinylpyrrolidone in polyethersulfone solution, the fabrication of microbeads via zeolite-mixing, electro-spraying and phase-inversion, and the subsequent aqueous-phase modifications based on ion-exchange and metal-leaching. An ultra-high (about 88%) amount of zeolite could be incorporated and well locked inside the polymer matrix. Potassium uptake capability was verified in water, normal saline and human serum, showing high selectivity and fast adsorption. The microbeads exhibited satisfying blood compatibility, negligible hemolysis ratio, prolonged clotting time, inhibited contact activation, and enhanced antifouling property toward serum proteins and cells. The proposed approach toward zeolite-heparin-mimicking-polymer hybrid microbeads provided a cheap, efficient and safe treatment protocol of hyperkalemia for the high-risk patients.
Current understanding of extrachromosomal circular DNA in cancer pathogenesis and therapeutic resistance
Authors: Yuanliang Yan, Guijie Guo, Jinzhou Huang, Ming Gao, Qian Zhu, Shuangshuang Zeng, Zhicheng Gong, Zhijie Xu
Journal: Journal of Hematology & Oncology (2020)

Abstract Extrachromosomal circular DNA was recently found to be particularly abundant in multiple human cancer cells, although its frequency varies among different tumor types. Elevated levels of extrachromosomal circular DNA have been considered an effective biomarker of cancer pathogenesis. Multiple reports have demonstrated that the amplification of oncogenes and therapeutic resistance genes located on extrachromosomal DNA is a frequent event that drives intratumoral genetic heterogeneity and provides a potential evolutionary advantage. This review highlights the current understanding of the extrachromosomal circular DNA present in the tissues and circulation of patients with advanced cancers and provides a detailed discussion of their substantial roles in tumor regulation. Confirming the presence of cancer-related extrachromosomal circular DNA would provide a putative testing strategy for the precision diagnosis and treatment of human malignancies in clinical practice.
Accelerated degradation of HAP/PLLA bone scaffold by PGA blending facilitates bioactivity and osteoconductivity
Authors: Cijun Shuai, Wenjing Yang, Pei Feng, Shuping Peng, Hao Pan
Journal: Bioactive Materials (2020)

The incorporation of hydroxyapatite (HAP) into poly-l-lactic acid (PLLA) matrix serving as bone scaffold is expected to exhibit bioactivity and osteoconductivity to those of the living bone. While too low degradation rate of HAP/PLLA scaffold hinders the activity because the embedded HAP in the PLLA matrix is difficult to contact and exchange ions with body fluid. In this study, biodegradable polymer poly (glycolic acid) (PGA) was blended into the HAP/PLLA scaffold fabricated by laser 3D printing to accelerate the degradation. The results indicated that the incorporation of PGA enhanced the degradation rate of scaffold as indicated by the weight loss increasing from 3.3% to 25.0% after immersion for 28 days, owing to the degradation of high hydrophilic PGA and the subsequent accelerated hydrolysis of PLLA chains. Moreover, a lot of pores produced by the degradation of the scaffold promoted the exposure of HAP from the matrix, which not only activated the deposition of bone like apatite on scaffold but also accelerated apatite growth. Cytocompatibility tests exhibited a good osteoblast adhesion, spreading and proliferation, suggesting the scaffold provided a suitable environment for cell cultivation. Furthermore, the scaffold displayed excellent bone defect repair capacity with the formation of abundant new bone tissue and blood vessel tissue, and both ends of defect region were bridged after 8 weeks of implantation.
Injectable and Self‐Healing Hydrogel with Anti‐Bacterial and Anti‐Inflammatory Properties for Acute Bacterial Rhinosinusitis with Micro Invasive Treatment
Authors: Zhengming Chen, Zhengwei Cai, Chengjing Zhu, Xianmin Song, Yanghua Qin, Minhui Zhu, Tao Zhang, Wenguo Cui, Haihong Tang, Hongliang Zheng
Journal: Advanced Healthcare Materials (2020)

Abstract Systemic antibiotic therapy is the main treatment for acute bacterial rhinosinusitis (ABRS). However, this treatment often causes side effects of dizziness, diarrhea, and drug resistance. In this study, a new polyethylene glycol hydrogel (PEG‐H) treatment model is developed to achieve sustained release of drugs at the locality while avoiding those adverse effects. The PEG‐H is composed of 4‐arm‐PEG‐SH and silver ions through a high affinity and dynamic reversible coordination bond between the thiol and silver ion. In the initial test, PEG‐H is loaded with Clarithromycin (CAM‐Lips@Hydrogel) or Clarithromycin and Budesonide liposomes (CAM+BUD‐Lips@Hydrogel). The results show that PEG‐H maintains the characteristics of self‐healing, biodegradability, moderate swelling rate, injectibility and sustained drug release. In in vivo studies, the hydrogel is injected into the maxillary sinus of ABRS rabbit models. In both a single or combined load, the hydrogel not only plays an effective role as an anti‐bacterial, but also inhibits inflammatory response of local sinus mucosa. In addition, no other side effects are observed in the ABRS rabbit model through behavioral observation and drug sensitivity tests. Therefore, the injectable self‐healing hydrogel with anti‐bacterial and anti‐inflammatory properties provides a new micro invasive therapeutic method for the clinical treatment of ABRS.