tbuckley/cabot-search huggingface dataset:
Invasive growth associated with cold-inducible RNA-binding protein expression drives recurrence of surgically resected brain metastases
Authors: Matthew Dankner, Maxime Caron, Tariq Al-Saadi, WenQing Yu, Véronique Ouellet, Rima Ezzeddine, Sarah M Maritan, Matthew G Annis, Phuong Uyen Le, Javad Nadaf, Noah S Neubarth, Paul Savage, Dongmei Zuo, Charles P Couturier, Jean Monlong, Haig Djambazian, Huda Altoukhi, Guillaume Bourque, Jiannis Ragoussis, Roberto J Diaz, Morag Park, Marie-Christine Guiot, Stephanie Lam, Kevin Petrecca, Peter M Siegel
Journal: Neuro-Oncology (2021)

Sixty percent of surgically resected brain metastases (BrM) recur within 1 year. These recurrences have long been thought to result from the dispersion of cancer cells during surgery. We tested the alternative hypothesis that invasion of cancer cells into the adjacent brain plays a significant role in local recurrence and shortened overall survival.We determined the invasion pattern of 164 surgically resected BrM and correlated with local recurrence and overall survival. We performed single-cell RNA sequencing (scRNAseq) of >15,000 cells from BrM and adjacent brain tissue. Validation of targets was performed with a novel cohort of BrM patient-derived xenografts (PDX) and patient tissues.We demonstrate that invasion of metastatic cancer cells into the adjacent brain is associated with local recurrence and shortened overall survival. scRNAseq of paired tumor and adjacent brain samples confirmed the existence of invasive cancer cells in the tumor-adjacent brain. Analysis of these cells identified cold-inducible RNA-binding protein (CIRBP) overexpression in invasive cancer cells compared to cancer cells located within the metastases. Applying PDX models that recapitulate the invasion pattern observed in patients, we show that CIRBP is overexpressed in highly invasive BrM and is required for efficient invasive growth in the brain.These data demonstrate peritumoral invasion as a driver of treatment failure in BrM that is functionally mediated by CIRBP. These findings improve our understanding of the biology underlying postoperative treatment failure and lay the groundwork for rational clinical trial development based upon invasion pattern in surgically resected BrM.
Abstract 13620: Loss of Pkm2 Alters Myocardial Glucose Levels Before and After Infarction
Authors: Allison L Williams, Lu Wang, Katie Lee, Abigail Avelar, Guoxiang Xie, Wei Jia, Ralph V Shohet
Journal: Circulation (2019)

Introduction: Pyruvate kinase is a key enzyme in glucose metabolism, converting phosphoenolpyruvate to pyruvate. The muscle-specific isoform (Pkm1) is highly expressed in the heart and directs pyru...
Genetic polymorphism of Glutathione S- Transferase M1 and T1 and risk to chronic myeloid leukemia
Authors: Prachi Bajpai, Deepa Agrawal, Anil Kumar Tripathi
Journal: Cancer Research (2006)

4588  Background - Chronic myeloid Leukemia (CML) is a clonal myeloproliferative disorder, and accounts for 15% of leukemias in adult . Inherited differences in the capacity of xenobiotic metabolizing enzymes, might be an important factor in genetic susceptibility to cancer.These interindividual differences may lead to susceptibility for number of cancers , hematologic malignancies being one of them. The Glutathione S - Transferases (GSTs) have been implicated as susceptibility genes in this context. The aim of our study was to examine whether polymorphic variation in GSTs confers susceptibility to CML. Study design - Multiplex PCR was carried out to determine the presence or deletion of GSTM1 and GSTT1. β globin was used as an internal positive control. PCR amplicons of 480, 268 and 215 base pair respectively was amplified. Absence of band signifies null genotype. PCR products was separated using ethidium bromide stained 2% agarose gel . The relationship between GSTM1, GSTT1 genotypes and risk of CML was assessed by means of odds ratio(OR) with 95% confidence limits calculated by logistic regression. Results -The frequency of GSTM1 and GSTT1 null alleles in controls was 26% (20/78) and 5% (4/78) respectively, which is in agreement with literature cited frequencies in Indian population. The frequency of GSTM1 and GSTT1 null alleles in cases was 31% (23/75) and 21% (16/75), respectively. Conclusions - The frequency of GSTT1 null genotypes was found statistically significant, and projects that GSTT1 null genotypes may be a risk factor to develop CML. Though GSTM1 null genotype frequency was higher in CML patients 31% as compared to 26% it did not attain formal statistical significance.
TLR9 expression in chronic lymphocytic leukemia identifies a promigratory subpopulation and novel therapeutic target
Authors: Emma Kennedy, Eve Coulter, Emma Halliwell, Nuria Profitos-Peleja, Elisabeth Walsby, Barnaby Clark, Elizabeth H. Phillips, Thomas A. Burley, Simon Mitchell, Stephen Devereux, Christopher D. Fegan, Christopher I. Jones, Rosalynd Johnston, Tim Chevassut, Ralph Schulz, Martina Seiffert, Angelo Agathanggelou, Ceri Oldreive, Nicholas Davies, Tatjana Stankovic, Triantafillos Liloglou, Chris Pepper, Andrea G. S. Pepper
Journal: Blood (2021)
Abstract 15915: A Sex and Race-Stratified Analysis of Mean Age of Hospitalizations and Subsequent All-Cause Mortality in Acute Myocardial Infarction
Authors: Samarthkumar J Thakkar, Rupak Desai, Manan Vyas, Ankit Vyas, Kartik Dhaduk, Rushik Bhuva
Journal: Circulation (2019)

Background: Inconsistent modern-day evidence incited us to examine all-cause mortality and mean age of hospitalization for acute myocardial infarction (AMI), stratified by sex and race. Methods: A ...
Inflammation Mediates the Development of Aggressive Breast Cancer Following Radiotherapy
Authors: Lin Ma, Alba Gonzalez-Junca, Yufei Zheng, Haoxu Ouyang, Irineu Illa-Bochaca, Kathleen C. Horst, Gregor Krings, Yinghao Wang, Ignacio Fernandez-Garcia, William Chou, Mary Helen Barcellos-Hoff
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Women treated with radiotherapy before 30 years of age have increased risk of developing breast cancer at an early age. Here, we sought to investigate mechanisms by which radiation promotes aggressive cancer. Experimental Design: The tumor microenvironment (TME) of breast cancers arising in women treated with radiotherapy for Hodgkin lymphoma was compared with that of sporadic breast cancers. To investigate radiation effects on carcinogenesis, we analyzed tumors arising from Trp53-null mammary transplants after irradiation of the target epithelium or host using immunocompetent and incompetent mice, some of which were treated with aspirin. Results: Compared with age-matched specimens of sporadic breast cancer, radiation-preceded breast cancers (RP-BC) were characterized by TME rich in TGFβ, cyclooxygenase 2, and myeloid cells, indicative of greater immunosuppression, even when matched for triple-negative status. The mechanism by which radiation impacts TME construction was investigated in carcinomas arising in mice bearing Trp53-null mammary transplants. Immunosuppressive TMEs (iTME) were recapitulated in mice irradiated before transplantation, which implicated systemic immune effects. In nu/nu mice lacking adaptive immunity irradiated before Trp53-null mammary transplantation, cancers also established an iTME, which pointed to a critical role for myeloid cells. Consistent with this, irradiated mammary glands contained more macrophages and human cells cocultured with polarized macrophages underwent dysplastic morphogenesis mediated by IFNγ. Treating mice with low-dose aspirin for 6 months postirradiation prevented establishment of an iTME and resulted in less aggressive tumors. Conclusions: These data show that radiation acts via nonmutational mechanisms to promote markedly immunosuppressive features of aggressive, RP-BCs.
The management of metastatic GIST: current standard and investigational therapeutics
Authors: Ciara M. Kelly, Laura Gutierrez Sainz, Ping Chi
Journal: Journal of Hematology & Oncology (2021)

Abstract Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. The majority of GISTs harbor gain of function mutations in either KIT or PDGFRα. Determination of the GIST molecular subtype upon diagnosis is important because this information informs therapeutic decisions in both the adjuvant and metastatic setting. The management of GIST was revolutionized by the introduction of imatinib, a KIT inhibitor, which has become the standard first line treatment for metastatic GIST. However, despite a clinical benefit rate of 80%, the majority of patients with GIST experience disease progression after 2–3 years of imatinib therapy. Second and third line options include sunitinib and regorafenib, respectively, and yield low response rates and limited clinical benefit. There have been recent FDA approvals for GIST including ripretinib in the fourth-line setting and avapritinib for PDGFRA exon 18-mutant GIST. This article aims to review the optimal treatment approach for the management of patients with advanced GIST. It examines the standard treatment options available but also explores the novel treatment approaches in the setting of imatinib refractory GIST.
Age Effect on Treatment Responses to 0.05%, 0.025%, and 0.01% Atropine
Authors: Fen Fen Li, Yuzhou Zhang, Xiujuan Zhang, Benjamin Hon Kei Yip, Shu Min Tang, Ka Wai Kam, Alvin L. Young, Li Jia Chen, Clement C. Tham, Chi Pui Pang, Jason C. Yam
Journal: Ophthalmology (2021)
Congenital Tracheoesophageal Fistula in an Adult
Authors: Seshiru Nakazawa, Toshiki Yajima, Ken Shirabe
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Congenital Tracheoesophageal Fistula in an Adult." American Journal of Respiratory and Critical Care Medicine, 203(7), pp. e27–e28
Reply to: Vitamin C as a promoter of γδ T cells
Authors: Léonce Kouakanou, Christian Peters, Dieter Kabelitz
Journal: Cellular and Molecular Immunology (2021)

Last year, we published a paper in this journal in which we described the effects of vitamin C and its phospho-modified version (phospho-vitamin C, pVC) on the in vitro activation, proliferation, and effector function of human γδ T cells. 1 We were delighted to see that our study was recently highlighted in a Comment in this journal by Meraviglia and Dieli, 2 underscoring the potential interest in using vitamin C to promote γδ T cell activity for use in cancer immunotherapy.Our study was a joint publication with our Chinese collaborators, headed by Prof. Zhinan Yin, with whom we share an interest in exploring the beneficial effects of vitamin C on boosting the cellular immune response.In fact, Yin and colleagues initiated clinical studies on the adoptive transfer of allogeneic γδ T cells expanded in the presence of vitamin C into cancer patients.A report of a clinical phase I study demonstrating the safety of allogeneic γδ T cell transfer has recently been published in this journal, another collaborative effort of our two groups. 3n their comment, Meraviglia and Dieli highlight the most important results of our study without even mentioning our group.The results related to the rescuing effect of vitamin C on phosphoantigen-restimulated γδ T cells that were discussed at length in the Comment and summarized in their Fig. 1 were entirely performed by the first author of our paper as part of a Ph.D. thesis in our group.It would have been appropriate to mention in the legend of their Fig. 1 that the figure is based on results reported in our paper. 1eraviglia and Dieli also comment on another recent paper by "the same authors", in which we showed that vitamin C induced hypomethylation of the FOXP3 locus in human γδ T cells activated in the presence of TGF-β. 4 In this context, the term "same authors" refers to their previous wording of "Yin and colleagues" throughout the Comment.Apparently, it has escaped the attention of Meraviglia and Dieli that Prof. Yin and our Chinese collaborators are not even coauthors on this paper.
Challenges of Cardio-Kidney Composite Outcomes in Large-Scale Clinical Trials
Authors: Ravi B. Patel, Jozine M. Ter Maaten, João Pedro Ferreira, Finnian R. McCausland, Sanjiv J. Shah, Patrick Rossignol, Scott D. Solomon, Muthiah Vaduganathan, Milton Packer, Aliza Thompson, Norman Stockbridge, Faiez Zannad
Journal: Circulation (2021)

Patients with chronic cardiovascular or metabolic diseases, including diabetes, hypertension, obesity, and heart failure, often have comorbid kidney disease. Long-term outcomes are worse in the setting of both cardiac and kidney disease compared with either disease in isolation. In addition, the clinical presentations of certain acute cardiovascular events (such as heart failure) and worsening kidney function overlap and may be challenging to distinguish. Recently, certain novel treatments have demonstrated beneficial effects on both cardiac and kidney outcomes. Sodium-glucose cotransporter-2 inhibitors have exhibited concordant risk reduction and clinically important benefits in chronic kidney disease with and without diabetes, diabetes and established cardiovascular disease or multiple atherosclerotic vascular disease risk factors, and heart failure with reduced ejection fraction with and without diabetes. Primary trial results have revealed that sacubitril-valsartan therapy improves cardiovascular outcomes in patients with chronic heart failure with reduced ejection fraction and post hoc analyses suggest favorable kidney effects. A concordant pattern of kidney benefit with sacubitril-valsartan has also been observed in chronic heart failure with preserved ejection fraction. Given the complex interplay between cardiac and kidney disease and the possibility that treatments may show concordant cardio-kidney benefits, there has been recent interest in formally acknowledging, defining, and using composite cardio-kidney outcomes in future cardiovascular trials. This review describes potential challenges in use of such outcomes that should be considered and addressed before their incorporation into such trials.
Abstract 16061: Mediating Factors in Racial Differences in Persistent Control of Hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Lindsay Pool, Gabriel Tajeu, Paul Muntner, Catarina Kiefe, Norrina B Allen
Journal: Circulation (2018)

Introduction: Awareness and treatment of hypertension is higher among blacks as compared to whites, but control rates are lower. The objective of this study was to identify explanatory factors for ...
Interventional Radiology for Local Immunotherapy in Oncology
Authors: Lambros Tselikas, Stephane Champiat, Rahul A. Sheth, Steve Yevich, Samy Ammari, Frederic Deschamps, Siham Farhane, Charles Roux, Sandrine Susini, Severine Mouraud, Alexandre Delpla, Thibault Raoult, Caroline Robert, Christophe Massard, Fabrice Barlesi, Jean-Charles Soria, Aurélien Marabelle, Thierry de Baere
Journal: Clinical Cancer Research (2021)

Abstract Human intratumoral immunotherapy (HIT-IT) is under rapid development, with promising preliminary results and high expectations for current phase III trials. While outcomes remain paramount for patients and the referring oncologists, the technical aspects of drug injection are critical to the interventional radiologist to ensure optimal and reproducible outcomes. The technical considerations for HIT-IT affect the safety, efficacy, and further development of this treatment option. Image-guided access to the tumor allows the therapeutic index of a treatment to be enhanced by increasing the intratumoral drug concentration while minimizing its systemic exposure and associated on-target off-tumor adverse events. Direct access to the tumor also enables the acquisition of cancer tissue for sequential sampling to better understand the pharmacodynamics of the injected immunotherapy and its efficacy through correlation of immune responses, pathologic responses, and imaging tumor response. The aim of this article is to share the technical insights of HIT-IT, with particular consideration for patient selection, lesion assessment, image guidance, and technical injection options. In addition, the organization of a standard patient workflow is discussed, so as to optimize HIT-IT outcome and the patient experience.
Correspondence on ‘Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine’
Authors: Sarthak Gupta, Shuichiro Nakabo, Jun Chu, Sarfaraz Hasni, Mariana J Kaplan
Journal: Annals of the Rheumatic Diseases (2021)

Correspondence on 'Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine'Mathian et al described the clinical course and heterogeneity of COVID-19 in 17 systemic lupus erythematosus (SLE) patients. 1SLE subjects could be at higher risk of developing COVID-19, with more severe symptomatology and need for hospitalisation due to multiple underlying risk factors. 1 2 Type-I interferons (IFN), including IFNα, play fundamental roles in immunity and are crucial in antiviral responses. 3Defects in IFN signalling pathways, secondary to monogenic inborn errors or to blocking autoantibodies, promote immunodeficiency and recurrent infections. 4 5Dysregulation in type-I IFN pathway also plays key pathogenic roles in SLE. 6A recent report showed association between anti-type-I IFN autoantibodies in 10% of subjects with life-threatening COVID-19 in the general population. 7A comprehensive evaluation of multiple anticytokine autoantibodies showed the presence of anti-type-I IFN autoantibodies in 11% of SLE subjects in the pre-COVID-19 era. 8We hypothesised that SLE patients having anti-IFNα autoantibodies at baseline (prior to 2020) may be at higher risk of developing COVID-19, and that the presence of these autoantibodies may help in guiding management and preventive strategies.Ten SLE females who developed COVID-19 between 1 April and 1 October 2020 were identified among lupus subjects followed at the National Institutes of Health, Bethesda, MD, USA under IRBapproved SLE natural history protocol 94-AR-0066 (online supplemental methods, table 1).Seven patients had mild to moderate COVID-19 symptoms that were managed at home with supportive care.Three patients had severe symptoms requiring hospitalisation, supplemental oxygen and/or steroids and convalescent plasma infusion.All patients had full recovery.Eight patients were on daily prednisone (range 5-20 mg/day) when COVID-19 symptoms developed.Seven patients were taking hydroxychloroquine prior to COVID-19 and continued it during the infection.One patient (patient 2) had received rituximab in February 2020 and developed COVID-19 in May 2020.Another patient (patient 9) developed COVID-19 while on belimumab.
Abstract 15674: Cardiovascular Manifestation and Its Association With In-hospital Outcome in Patients Admitted in Intensive Care With Covid19: Middle Eastern Country Multicenter Data
Authors: Fahad Alkindi, khamis alhashmi, Salma Alharthi, khalid alsaidi, shabib alasmi, Tasneem Alrashdi, Huda Alkhalili, Feryal Khamis, Adil Algafri, Sultan Allawati, muzna alfarsi, Sathiya Murthi, Mujahid Al busaidi, Abdullah balkhair, Hafidh Alhadi, khalid Alrasadi, Hilal Alsabti
Journal: Circulation (2020)

Introduction: The world has experienced an outbreak of coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The middle east countries were hit like the rest of the world with this pandemic. Hypothesis: In-hospital mortality has been reported in many countries, but similar reports from middle eastern countries have not been well described. Methods: In this retrospective, multicentre cohort study, we included all adult hospitalized in the intensive care Unit with laboratory-confirmed COVID-19 in the two main hospitals in Oman, Sultan Qaboos University Hospital SQUH and Royal Hospital RH between the period of 1 st of March to May 30 th , 2020. Demographic, clinical presentation, treatment and outcome, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings: 153 patients admitted in ICU ,60 from SQUH and 93 from RH were included in this study, of whom 131 (85.6%) were discharged and 22 (14.3%) died in hospital. The mean age of the patients was 49.56±15.20. Males were accounted 126 (83.4%) and females were 25 (16.6%). Nearly 40% of them were Omani citizens and rest of 60% were residents of Oman. Those who have history of coronary artery disease found to have higher in hospital mortality rate OR= 4.09, 95% C.I 1.57-10.6) in which mortality in patients on aspirin was (31.8% in non-survival group vs 10.8% in survival group, p=0.047), clopedogril (18.2% vs 2.3%, p=0.009) and statin (31.8% vs 10.6%, p=0.016)At presentation, non-survivals were found to have significantly higher troponin with the risk of 7.07 (C.I. 2.09-23.92. p=0.002). In fact, patients with high sensitivity troponin rise &gt;100 ng/L were more likely to die 5.83 times than the group with troponin &lt;100 ng/L. Conclusion: History of coronary artery disease and rise of high sensitivity troponin during admission found to be strongly associated with in-hospital mortality. Rise of high sensitivity troponin of greater than &gt;100ng/L was independent risk factors for death of COVID-19. Identifying these risk factors could help to assess the prognosis of these patients at early stage.
IIb or Not IIb: Is There a Place for Pre-Hospital Tirofiban in ST-Segment Elevation Myocardial Infarction Patients?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Ron Waksman
Journal: Journal of the American College of Cardiology (2010)
Focus on education and wellbeing to aid specialty recruitment
Authors: Ricky Ellis, Reena Ellis
Journal: BMJ (2021)

We echo the concerns of the Royal College of Anaesthetists about the workforce gap in anaesthetics.1 This problem is not exclusive to anaesthesia and exists in many specialties; the NHS was experiencing a workforce crisis long before the covid-19 pandemic.2 Consultant posts are unfilled across the UK, yet specialty training remains a bottleneck because of the lack of specialty …
Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection
Authors: Nina Hensel, Zuguang Gu, None Sagar, Dominik Wieland, Katharina Jechow, Janine Kemming, Sian Llewellyn-Lacey, Emma Gostick, Oezlem Sogukpinar, Florian Emmerich, David A. Price, Bertram Bengsch, Tobias Boettler, Christoph Neumann-Haefelin, Roland Eils, Christian Conrad, Ralf Bartenschlager, Dominic Grün, Naveed Ishaque, Robert Thimme, Maike Hofmann
Journal: Nature Immunology (2021)
The Purdue Pharma Opioid Settlement — Accountability, or Just the Cost of Doing Business?
Authors: Corey S. Davis
Journal: New England Journal of Medicine (2021)

Interview with Corey Davis on the recent federal settlement with Purdue Pharma over its actions to increase prescriptions of its opioid medications. (09:12)Download Over the objections of numerous members of Congress, state attorneys general, and families of people killed by opioid products, the company was permitted to resolve all federal criminal and civil charges and its owners, members of the Sackler family, were permitted to settle all federal civil claims against them.