tbuckley/cabot-search huggingface dataset:
First Identified Cases of SARS-CoV-2 Variant P.1 in the United States — Minnesota, January 2021
Authors: Melanie J. Firestone, Alexandra J. Lorentz, Stephanie Meyer, Xiong Wang,, Kathryn Como-Sabetti, Sara Vetter, Kirk Smith,, Stacy Holzbauer, Amanda Beaudoin, Jacob Garfin, Kristin Ehresmann, Richard Danila, Ruth Lynfield
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Since December 2020, the Minnesota Department of Health (MDH) Public Health Laboratory has been receiving 100 specimens per week (50 from each of two clinical partners) with low cycle threshold (Ct) values for routine surveillance for SARS-CoV-2, the virus that causes COVID-19. On January 25, 2021, MDH identified the SARS-CoV-2 variant P.1 in one specimen through this surveillance system using whole genome sequencing, representing the first identified case of this variant in the United States. The P.1 variant was first identified in travelers from Brazil during routine airport screening in Tokyo, Japan, in early January 2021 (1). This variant has been associated with increased transmissibility (2), and there are concerns that mutations in the spike protein receptor-binding domain might disrupt both vaccine-induced and natural immunity (3,4). As of February 28, 2021, a total of 10 P.1 cases had been identified in the United States, including the two cases described in this report, followed by one case each in Alaska, Florida, Maryland, and Oklahoma (5).
Abstract PO041: Hyaluronan processing and function in the progression of breast cancer
Authors: Patrice M. Witschen, Thomas S. Chaffee, Nicholas J. Brady, Todd P. Knutson, Rebecca S. LaRue, Sarah Munro, Lyubov Tiegs, James B. McCarthy, Andrew C. Nelson, Kathryn L. Schwertfeger
Journal: Cancer Research (2021)

Abstract Hyaluronan (HA) is a large, soluble, glycosaminoglycan of the extracellular matrix that has anti-inflammatory effects under physiologic conditions. However, HA is cleaved into low molecular weight (LMW) fragments under conditions of cellular or organismal stress, acting as a molecular “switch” that promotes inflammation. In breast cancer, a decrease in HA synthesis has been correlated with decreased tumor cell proliferation and migration. However, the roles of HA fragmentation in the progression of breast cancer are unknown. We predict that HA fragmentation increases during this transition, promoting inflammation through LMW HA-CD44 interactions. To test our hypothesis, the presence/absence of HA fragmentation was determined using gel electrophoresis in breast cancer cell lines. Additionally, qRT-PCR was performed to examine gene expression of the three major hyaluronan synthases (Has) 1-3 and the three major hyaluronidases (Hyal) 1, 2, and PH-20. Our data suggest as a cancerous lesion progresses, HMW HA production increases (primarily through Has2), but HA fragmentation does not occur until the tumor acquires a more aggressive phenotype (primarily through Hyal1). Following characterization of HA fragmentation and machinery within our system, we found changes in inflammatory cytokines (such as CCL2) as downstream effects of CD44 and HA synthesis inhibition. We have currently knocked out CD44 in two breast cancer cell lines using the CRISPR/Cas9 method to determine the functional relationship between CD44 and HA using an in vivo mouse model. By targeting HA-CD44 signaling associated with inflammation, new therapeutic approaches can be developed for the treatment of breast cancer. Citation Format: Patrice M. Witschen, Thomas S. Chaffee, Nicholas J. Brady, Todd P. Knutson, Rebecca S. LaRue, Sarah Munro, Lyubov Tiegs, James B. McCarthy, Andrew C. Nelson, Kathryn L. Schwertfeger. Hyaluronan processing and function in the progression of breast cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO041.
<i>Lactobacillus rhamnosus</i> GG induces cGAS/STING- dependent type I interferon and improves response to immune checkpoint blockade
Authors: Wei Si, Hua Liang, Jason Bugno, Qi Xu, Xingchen Ding, Kaiting Yang, Yanbin Fu, Ralph R Weichselbaum, Xin Zhao, Liangliang Wang
Journal: Gut (2021)

Objective Our goals were to evaluate the antitumour efficacy of Lactobacillus rhamnosus GG (LGG) in combination with immune checkpoint blockade (ICB) immunotherapies on tumour growth and to investigate the underlying mechanisms. Design We used murine models of colorectal cancer and melanoma to evaluate whether oral administration of LGG improves the efficacy of ICB therapies. We performed the whole genome shotgun metagenome sequencing of intestinal contents and RNA sequencing of dendritic cells (DCs). In a series of in vitro and in vivo experiments, we further defined the immunological and molecular mechanisms of LGG-mediated antitumour immunity. Results We demonstrate that oral administration of live LGG augmented the antitumour activity of anti-programmed cell death 1 (PD-1) immunotherapy by increasing tumour-infiltrating DCs and T cells. Moreover, the combination treatment shifted the gut microbial community towards enrichment in Lactobacillus murinus and Bacteroides uniformis , that are known to increase DC activation and CD8 + tumour recruitment. Mechanistically, treatment with live LGG alone or in combination with anti-PD-1 antibody triggered type I interferon (IFN) production in DCs, enhancing the cross-priming of antitumour CD8 + T cells. In DCs, cyclic GMP-AMP synthase (cGAS)/stimulator of IFN genes (STING) was required for IFN-β induction in response to LGG, as evidenced by the significant decrease in IFN-β levels in cGAS or STING-deficient DCs. LGG induces IFN-β production via the cGAS/STING/TANK binding kinase 1/interferon regulatory factor 7 axis in DCs. Conclusion Our findings have offered valuable insight into the molecular mechanisms of live LGG-mediated antitumour immunity and establish an empirical basis for developing oral administration of live LGG as a combination agent with ICB for cancer therapies.
Phase II trial of stereotactic ablative radiation (SAbR) for oligometastatic kidney cancer.
Authors: Raquibul Hannan, Michael Christensen, Liliana Robles, Alana Christie, Aurelie Garant, Neil Bipinchandra Desai, Hans J. Hammers, Waddah Arafat, Isaac Alexander Bowman, Suzanne Cole, Kevin Dale Courtney, Solomon L. Woldu, Aditya Bagrodia, Vitaly Margulis, Jeffrey A Cadeddu, Hak Choy, David Sher, James Brugarolas
Journal: Journal of Clinical Oncology (2021)

311 Background: Stereotactic ablative radiotherapy (SAbR) is a promising treatment option for selected oligometastatic renal cell carcinoma (RCC) patients that can provide longitudinal disease control while preserving quality of life. Retrospective data have shown a local control (LC) rate greater than 90% and longitudinal disease control of over a year without systemic therapy. However, prospective validation of SAbR for oligometastatic RCC is lacking. In this prospective phase II single arm trial, we evaluated the impact of SAbR on freedom from systemic therapy (FFST). Methods: Treatment naïve patients with RCC confirmed by pathology and radiographic evidence of three or fewer extracranial metastases received SAbR with curative intent to all measurable sites of disease. Follow-up included radiographic imaging at three-month intervals to assess disease control. The primary endpoint was FFST defined as time from SAbR to the initiation of systemic therapy. Secondary endpoints included LC, modified progression-free survival (mPFS) (time from first SAbR to progression not amenable to further SAbR), PFS on subsequent systemic therapy, cancer-specific survival (CSS), overall survival (OS), toxicity and health-related quality of life (QOL) indices as measured with EQ-5D-5L and FACT-G. A Wilcoxon signed-rank test was used to evaluate the QOL indices. Results: The trial completed accrual with the enrollment of 23 patients who received SAbR to a total of 38 sites. At a median follow-up of 12 months (interquartile range 1.8-16), 1-year FFST was 87% (95% CI: 56%-96%). The 1-year mPFS was 79% (95% CI:49%-93%), while the median mPFS has not yet been reached. Three patients had disease progression at individual time points of 3.5, 4.0, and 12 months. One of these patients developed brain metastases that were controlled with gamma knife radiosurgery without initiating systemic therapy. The LC, CSS, and OS were 100% (38/38), 100% (23/23), and 95% (22/23), respectively. When compared to baseline, no significant decline in QOL was detected. Three patients experienced treatment-related grade 1 toxicity; no ≥grade 2 toxicities were reported. One patient died of an unrelated cause. Conclusions: SAbR is a safe and effective treatment for oligometastatic RCC that can provide longitudinal disease control and preserve quality of life. These data support further evaluation of SAbR for oligometastatic RCC in a randomized study. Clinical trial information: NCT02956798 .
Updated treatment recommendations for hepatocellular carcinoma (HCC) from the ESMO Clinical Practice Guidelines
Authors: A. Vogel, E. Martinelli, A. Vogel, A. Cervantes, I. Chau, B. Daniele, J.M. Llovet, T. Meyer, J.-C. Nault, U. Neumann, J. Ricke, B. Sangro, P. Schirmacher, C. Verslype, C.J. Zech, D. Arnold, E. Martinelli
Journal: Annals of Oncology (2021)
The burden of progressive fibrotic interstitial lung disease across the UK
Authors: Thomas Simpson, Shaney L. Barratt, Paul Beirne, Nazia Chaudhuri, Anjali Crawshaw, Louise E. Crowley, Sophie Fletcher, Michael A. Gibbons, Philippa Hallchurch, Laura Horgan, Ieva Jakaityte, Thomas Lewis, Tom McLellan, Katherine J. Myall, Ryan Miller, David J.F. Smith, Stefan Stanel, Muhunthan Thillai, Fiona Thompson, Timothy Wallis, Zhe Wu, Philip L. Molyneaux, Alex G. West
Journal: European Respiratory Journal (2021)

While idiopathic pulmonary fibrosis (IPF) remains the exemplar progressive fibrotic lung disease, there remains a cohort of non-IPF fibrotic lung diseases (fILD) which adopt a similar clinical behaviour to IPF despite therapy [1]. This phenotypically related group of conditions, where progression of disease is similar to that seen in IPF, have recently been described as progressive fibrotic interstitial lung diseases (PF-ILD) [2]. Historically, treatments for these cases have been limited though given the phenotypic similarities many cases may have been given a multidisciplinary working diagnosis of IPF based on their disease behaviour [3]. The INBUILD trial broadened the scope of treatable fILD by demonstrating a significant benefit of Nintedanib in patients with fILD and progressive disease [4]. In response to this the European Commission approved an additional indication for nintedanib in adults for the treatment of PF-ILD in July 2020. Almost 15% of new referrals with non-IPF fibrotic ILD go on to develop a progressive fibrotic phenotype and would benefit from antifibrotic therapy <https://bit.ly/3uPhClN>
Headache, Cognitive Decline, and a Curious Rim-Enhancing Lesion
Authors: Charles B. Beaman, Antonio Spagnolo-Allende, Chun-Chieh Lin
Journal: JAMA Neurology (2021)

A 75-year-old man presents with severe, persistent headache and right eye pain, with a large T2-hyperintense lesion in the right temporoparietal region and an increased diffusion-weighted imaging signal on magnetic resonance imaging. What is your diagnosis?
Non-alcoholic fatty liver disease and increased risk of incident extrahepatic cancers: a meta-analysis of observational cohort studies
Authors: Alessandro Mantovani, Graziana Petracca, Giorgia Beatrice, Alessandro Csermely, Herbert Tilg, Christopher D Byrne, Giovanni Targher
Journal: Gut (2021)

We performed a meta-analysis of observational studies to quantify the magnitude of the association between non-alcoholic fatty liver disease (NAFLD) and risk of extrahepatic cancers.
Re: Philip Cornford, Roderick C.N. van den Bergh, Erik Briers, et al. EAU-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II—2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer. Eur Urol 2021;79:263–82
Authors: Finn Edler von Eyben
Journal: European Urology (2021)
Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial
Authors: Mikael Mazighi, Sebastien Richard, Bertrand Lapergue, Igor Sibon, Benjamin Gory, Jerome Berge, Arturo Consoli, Julien Labreuche, Jean-Marc Olivot, Joseph Broderick, Alain Duhamel, Emmanuel Touze, Adnan I Qureshi, Amélie Yavchitz, Simon Escalard, Jean-Philippe Desilles, Hocine Redjem, Stanislas Smajda, Robert Fahed, Solène Hébert, Benjamin Maïer, François Delvoye, Perrine Boursin, Malek Ben Maacha, Michael Obadia, Candice Sabben, Raphael Blanc, Julien Savatovsky, Michel Piotin, Mikael Mazighi, Michel Piotin, Raphael Blanc, Hocine Redjem, Benjamin Maïer, Jean-Philippe Desilles, Simon Escalard, Stanislas Smajda, François Delvoye, Solène Hebert, Michael Obadia, Candice Sabben, Alexandre Obadia, Igor Raynouard, Erwan Morvan, Perrine Boursin, Malek Ben Maacha, Bertrand Lapergue, Arturo Consoli, Adrien Wang, Benjamin Gory, Sebastien Richard, Gioia Mione, Lisa Humbertjean, Matthieu Bonnerot, Jean-Christophe Lacour, René Anxionnat, Romain Tonnelet, Serge Bracard, Xavier Barreau, Gaultier Marnat, Jérôme Berge, Ludovic Lucas, Pauline Renou, Sabrina Debruxelles, Mathilde Poli, Sharmila Sagnier
Journal: The Lancet Neurology (2021)
Association of statins and nivolumab activity in patients with metastatic renal cell carcinoma (mRCC): Results from the phase II nivoren—GETUG AFU 26 trial.
Authors: Emeline Colomba, Ronan Flippot, Cécile Dalban, Sylvie Negrier, Christine Chevreau, Gwenaelle Gravis, Stephane Oudard, Brigitte Laguerre, Philippe Barthelemy, Marine Gross Goupil, Lionnel Geoffrois, Frederic Rolland, Antoine Thiery-Vuillemin, Florence Joly, Sylvain Ladoire, Florence Tantot, Bernard Escudier, Laurence Albiges
Journal: Journal of Clinical Oncology (2021)

359 Background: Statins are HMG-CoA inhibitors that regulate several mechanisms involved in tumor growth, including mitochondrial metabolism, activation of oncogenic signaling pathways, and immune modulation. Population-based studies showed that statin intake may be negatively associated with RCC onset. The impact of statins on response to immunotherapy in mRCC is unknown. Herein we study the association between statin administration and outcomes in patients with mRCC treated with nivolumab in the NIVOREN-GETUG AFU 26 phase II trial (NCT03013335). Methods: Patients with mRCC who failed previous VEGFR inhibitors were included. We assessed nivolumab activity, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) according to statin intake at baseline. Toxicity was assessed using CTCAE v4.0. Results: Overall,133 patients were treated with statins at baseline among 702 evaluable for concomitant therapies (19%). Among them, median age was 68 (49-90), 84% were male, 85% had a performance status ≥ 80%, 42% were overweight and 20% obese. Patients treated with statins had mostly good (23%) or intermediate (58%) IMDC risk, 64% had grade 3 or 4 tumors, and nivolumab was given in a third line setting or more in 55%. Median follow-up was 23.9 months (95%CI 23.0-24.5) in the overall cohort. The ORR was 26% in patients treated with statins, PFS 5.0 months (CI95% 3.0 – 5.5), OS 27.9 months (CI95% 19.4-30.3). Outcomes of patients with or without statins did not differ significantly. Similar rates of grade 3-5 TRAE were reported in patients with (20%) or without (18%) statin intake. Conclusions: This is the first study to evaluate statin intake and outcomes with nivolumab in patients with mRCC. Despite numerically higher ORR, statins were not significantly associated with improved outcomes. These data require other analyzes considering other factors such as BMI and other comorbidities. Further studies may help better understand the interplay between immunity and metabolic reprogramming in RCC.
The Genomic Architecture of Adaptation to Larval Malnutrition Points to a Trade-off with Adult Starvation Resistance in <i>Drosophila</i>
Authors: Tadeusz J. Kawecki, Berra Erkosar, Cindy Dupuis, Brian Hollis, R. Craig Stillwell, Martin Kapun
Journal: Molecular Biology and Evolution (2021)

Abstract Periods of nutrient shortage impose strong selection on animal populations. Experimental studies of genetic adaptation to nutrient shortage largely focus on resistance to acute starvation at adult stage; it is not clear how conclusions drawn from these studies extrapolate to other forms of nutritional stress. We studied the genomic signature of adaptation to chronic juvenile malnutrition in six populations of Drosophila melanogaster evolved for 150 generations on an extremely nutrient-poor larval diet. Comparison with control populations evolved on standard food revealed repeatable genomic differentiation between the two set of population, involving &amp;gt;3,000 candidate SNPs forming &amp;gt;100 independently evolving clusters. The candidate genomic regions were enriched in genes implicated in hormone, carbohydrate, and lipid metabolism, including some with known effects on fitness-related life-history traits. Rather than being close to fixation, a substantial fraction of candidate SNPs segregated at intermediate allele frequencies in all malnutrition-adapted populations. This, together with patterns of among-population variation in allele frequencies and estimates of Tajima’s D, suggests that the poor diet results in balancing selection on some genomic regions. Our candidate genes for tolerance to larval malnutrition showed a high overlap with genes previously implicated in acute starvation resistance. However, adaptation to larval malnutrition in our study was associated with reduced tolerance to acute adult starvation. Thus, rather than reflecting synergy, the shared genomic architecture appears to mediate an evolutionary trade-off between tolerances to these two forms of nutritional stress.
A retrospective study of primitive neuroectodermal tumor (PNET) of the kidney in a tertiary cancer center in India.
Authors: Nandini Sharrel Menon, Devanshi Kalra, Kumar Prabhash, Vanita Noronha, Santosh Menon, Ganesh Bakshi, Gagan Prakash, Mahendra Pal, Siddhartha Laskar, Nehal Rishi Khanna, Archi Agrawal, Amit Joshi
Journal: Journal of Clinical Oncology (2021)

361 Background: Primitive neuroectodermal tumours (PNET) of the kidney are rare tumours with aggressive behaviour. This study was conducted to review the diagnosis and management of patients with renal PNET at our centre. Methods: This was a retrospective study conducted at a tertiary cancer care centre in Mumbai, India. The demographic and clinical data of 17 patients treated by the uro-oncology services were retrieved from electronic medical records. Descriptive analysis was performed for baseline characteristics.Overall &amp; progression-free survival was determined using the Kaplan Meier method. Cox regression was used for multivariate analysis. Results: There were 12 male and 5 female patients in this cohort with a median age of 27 years. At diagnosis 2 patients had metastatic disease and 15 patients had non-metastatic disease. Median follow up in this cohort was 22 months (range 2-30 months). Presenting complaints were hematuria, abdominal pain, flank pain, fever, bone pain, and incidentally detected renal mass. All patients were Mic -2 positive and 13 were FLI-1 positive on immunohistochemistry. Fourteen patients underwent radical nephrectomy. One (5.9%) patient received both neoadjuvant and adjuvant chemotherapy, 8 (47.1%) received adjuvant and 2 (11.8%) received palliative chemotherapy upfront. Eight patients received adjuvant radiation to the renal bed.There was disease progression in12 patients,10 of 15 patients with non metastatic disease at diagnosis eventually developed metastasis.The median progression free survival (PFS) was 10.55 months.The pathological feature that was associated with a shorter PFS was tumor size ⩾10 cm(p = 0.044).The median overall survival was 20.04 months (95% CI 9.49 -not reached). The presence of metastasis and treatment received significantly impacted overall survival (OS). Median OS in patients with non-metastatic disease was not reached versus 14.1 months in those with metastatic disease (p = .019).The median OS in patients treated with multimodality approach was 20.11 months. Patients did not undergo surgery had a median OS of 5.45 months (p &lt; .001) and those who did not receive any chemotherapy had a median OS of 4.57 months (p = .024).Thus, patients who received multimodality treatment had better outcomes. Conclusions: PNET kidney is an aggressive tumor which should be treated with a multimodality approach. Tumor size ⩾10 cm was an adverse prognostic factor.
Novel Application of Predictive Modeling: A Tailored Approach to Promoting HCC Surveillance in Patients With Cirrhosis
Authors: Amit G. Singal, Yixing Chen, Shrihari Sridhar, Vikas Mittal, Hannah Fullington, Muzeeb Shaik, Akbar K. Waljee, Jasmin Tiro
Journal: Clinical Gastroenterology and Hepatology (2021)
Photodynamic Therapy: Radioiodinated Persistent Luminescence Nanoplatform for Radiation‐Induced Photodynamic Therapy and Radiotherapy (Adv. Healthcare Mater. 5/2021)
Authors: Qiang Wang, Nian Liu, Zhenyu Hou, Junpeng Shi, Xinhui Su, Xiaolian Sun
Journal: Advanced Healthcare Materials (2021)

In article number 2000802 by Xinhui Su, Xiaolian Sun, and co-workers, a 131I labeled ZnPc(COOH)4 conjugated ZnGa2O4:Cr3+ nanoplatform (131I-ZGCs-ZnPcC4) is developed for in vivo radiotherapy (RT) and radiation-induced photodynamic therapy (PDT). 131I can not only activate ZGCs for long-lasting luminescence which further continuously activates the photosensitizer for PDT, but also can directly kill cancerous cells. Combining self-activated PDT and RT, it is believed that the 131IZGCs- ZnPcC4 can greatly benefit deep tumor therapy.
Immune Checkpoint Inhibitor‐Based Strategies for Synergistic Cancer Therapy
Authors: Mengying He, Tao Yang, Yuhan Wang, Mengyuan Wang, Xingye Chen, Dawei Ding, Yiran Zheng, Huabing Chen
Journal: Advanced Healthcare Materials (2021)

Abstract Immune checkpoint blockade therapy (ICBT) targeting checkpoints, such as, cytotoxic T‐lymphocyte associated protein‐4 (CTLA‐4), programmed death‐1 (PD‐1), or programmed death‐ligand 1 (PD‐L1), can yield durable immune response in various types of cancers and has gained constantly increasing research interests in recent years. However, the efficacy of ICBT alone is limited by low response rate and immune‐related side effects. Emerging preclinical and clinical studies reveal that chemotherapy, radiotherapy, phototherapy, or other immunotherapies can reprogramm immunologically “cold” tumor microenvironment into a “hot” one, thus synergizing with ICBT. In this review, the working principle and current development of various immune checkpoint inhibitors are summarized, while the interactive mechanism and recent progress of ICBT‐based synergistic therapies with other immunotherapy, chemotherapy, phototherapy, and radiotherapy in fundamental and clinical studies in the past 5 years are depicted and highlighted. Moreover, the potential issues in current studies of ICBT‐based synergistic therapies and future perspectives are also discussed.