tbuckley/cabot-search huggingface dataset:
Hyal2 Expression in Tumor-Associated Myeloid Cells Mediates Cancer-Related Inflammation in Bladder Cancer
Authors: Paul R. Dominguez-Gutierrez, Elizabeth P. Kwenda, William Donelan, Padraic O'Malley, Paul L. Crispen, Sergei Kusmartsev
Journal: Cancer Research (2020)

The increased presence of myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) in tumor tissue has been extensively reported. However, their role in the regulation of hyaluronan (HA) metabolism in the tumor microenvironment has not been established. Here we describe a novel function of tumor-associated myeloid cells related to the enhanced breakdown of extracellular HA in human bladder cancer tissue, leading to the accumulation of small HA fragments with molecular weight (MW) <20 kDa. Increased fragmentation of extracellular HA and accumulation of low molecular weight HA (LMW-HA) in tumor tissue was associated with elevated production of multiple inflammatory cytokines, chemokines, and angiogenic factors. The fragmentation of HA by myeloid cells was mediated by the membrane-bound enzyme hyaluronidase 2 (Hyal2). Increased numbers of Hyal2+CD11b+ myeloid cells were detected in the tumor tissue as well as in the peripheral blood of patients with bladder cancer. Coexpression of CD33 suggested that these cells belong to monocytic myeloid-derived suppressor cells. The HA-degrading function of Hyal2-expressing MDSCs could be enhanced by exposure to tumor-conditioned medium, and IL1β was identified as one of the factors involved in the stimulation of Hyal2 activity. CD44-mediated signaling played an important role in the regulation of HA-degrading activity of Hyal2-expressing myeloid cells, as the engagement of CD44 receptor with specific mAb triggered translocation of Hyal2 enzyme to the cellular surface and stimulated secretion of IL1β. Taken together, this work identifies Hyal2-expressing tumor-associated myeloid cells as key players in the accumulation of LMW-HA in the tumor microenvironment and cancer-related inflammation and angiogenesis. SIGNIFICANCE: This study identifies Hyal2-expressing tumor-associated myeloid cells of monocyte-macrophage lineage as contributors to hyaluronan degradation in bladder cancer tissue, leading to accumulation of inflammatory and proangiogenic low molecular weight hyaluronan fragments.
Abstract IA20: Lymph protects metastasizing melanoma cells from ferroptosis
Authors: Sean J. Morrison
Journal: Cancer Research (2020)

Abstract Cancer cells, including melanoma, often metastasize regionally through lymphatics before metastasizing systemically through the blood; however, the reason for this is unclear. We discovered that melanoma cells in lymph experience less oxidative stress and form more metastases than melanoma cells in blood. Immunocompromised mice with patient-derived melanomas and immunocompetent mice with mouse melanomas had more melanoma cells per microliter of tumor-draining lymph than tumor-draining blood. Cells metastasizing through blood, but not lymph, became dependent on the ferroptosis inhibitor GPX4. Cells pre-treated with chemical ferroptosis inhibitors formed more metastases than untreated cells after intravenous, but not intralymphatic, injection. We observed multiple differences between lymph fluid and blood plasma that may contribute to decreased oxidative stress and ferroptosis in lymph, including higher levels of glutathione and oleic acid, and less free iron, in lymph. Oleic acid protected melanoma cells from ferroptosis in an Acsl3-dependent manner and increased their capacity to form metastatic tumors. Melanoma cells from lymph nodes were more resistant to ferroptosis and formed more metastases after intravenous injection than melanoma cells from subcutaneous tumors. Exposure to the lymphatic environment thus protects melanoma cells from ferroptosis and increases their ability to survive during subsequent metastasis through the blood. Citation Format: Sean J. Morrison. Lymph protects metastasizing melanoma cells from ferroptosis [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA20.
Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic
Authors: Thomas Hubiche, Nathalie Cardot-Leccia, Florence Le Duff, Barbara Seitz-Polski, Pascal Giordana, Christine Chiaverini, Valérie Giordanengo, Géraldine Gonfrier, Vincent Raimondi, Olivier Bausset, Zoubir Adjtoutah, Margaux Garnier, Fanny Burel-Vandenbos, Bérengère Dadone-Montaudié, Véréna Fassbender, Aurélia Palladini, Johan Courjon, Véronique Mondain, Julie Contenti, Jean Dellamonica, Georges Leftheriotis, Thierry Passeron
Journal: JAMA Dermatology (2020)

Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown.To perform a systematic clinical, histologic, and biologic assessment in a cohort of patients with chilblain-like lesions occurring during the COVID-19 pandemic.In this prospective case series carried out with a COVID-19 multidisciplinary consultation group at the University Hospital of Nice, France, 40 consecutive patients presenting with chilblain-like lesions were included.Patients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-α) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis.Overall, 40 consecutive patients with chilblain-like lesions were included. Most patients were young, with a median (range) age of 22 (12-67) years; 19 were male and 21 were female. The clinical presentation was highly reproducible with chilblain-like lesions mostly on the toes. Bullous and necrotic evolution was observed in 11 patients. Acrocyanosis or cold toes were reported in 19 (47.5%) cases. Criteria compatible with COVID-19 cases were noted in 11 (27.5%) within 6 weeks prior to the eruption. The real-time PCR (rt-PCR) testing results were negative in all cases. Overall, SARS-CoV-2 serology results were positive in 12 patients (30%). D-dimer concentration levels were elevated in 24 (60.0%) cases. Cryoglobulinemia and parvovirus B19 serologic results were negative for all tested patients. The major histologic findings were features of lymphocytic inflammation and vascular damage with thickening of venule walls and pericyte hyperplasia. A significant increase of IFN-α production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19.Taken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy.ClinicalTrials.gov Identifier: NCT04344119.
Changing causes of death in Pennsylvania's hemophiliacs 1976 to 1991: impact of liver disease and acquired immunodeficiency syndrome [letter]
Authors: ME Eyster, JH Schaefer, MV Ragni, TJ Gorenc, S Shapiro, S Cutter, MK Kajani, J Abrams, LE Barron, A Odenwelder
Journal: Blood (1992)
Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes*
Authors: K.A. Reynolds, D.I. Schlessinger, A.F. Yanes, V. Godinez‐Puig, B.R. Chen, A.O. Kurta, J.K. Cotseones, S.G. Chiren, S. Iyengar, S.A. Ibrahim, B.Y. Kang, B. Worley, R. Behshad, D.M. DeHoratius, P. Denes, A.M. Drucker, L.M. Dzubow, J.R. Etzkorn, C.A. Harwood, J.Y.S. Kim, N. Lawrence, E.H. Lee, G.S. Lissner, A.A. Marghoob, A. Guminiski, R.N. Matin, A.R. Mattox, B.B. Mittal, J.R. Thomas, X.A. Zhou, D. Zloty, B.G.M. Hughes, M.K. Nottage, A.C. Green, A.A.E. Testori, G. Argenziano, C. Longo, I. Zalaudek, C. Lebbe, J. Malvehy, P. Saiag, S.S. Cernea, J. Schmitt, J.J. Kirkham, E. Poon, J.F. Sobanko, T.V. Cartee, I.A. Maher, M. Alam
Journal: British Journal of Dermatology (2020)

The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials.To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC.One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants.A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival.In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.
421P A multicenter, randomized, double-blind, placebo (PBO)-controlled, phase III trial of lenvatinib (LEN) in patients (pts) with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in China
Authors: M. Gao, M. Ge, Z. Xu, Q. Ji, F. Shi, J. Qin, F. Wang, G. Chen, Y. Zhang, R. Huang, J. Tan, T. Huang, S. Li, Z. Lv, Y. Lin, Z. Guo, T. Kubota, T. Suzuki, H. Ikezawa, X. Zheng
Journal: Annals of Oncology (2020)
Author Correction: Age-associated mitochondrial DNA mutations cause metabolic remodeling that contributes to accelerated intestinal tumorigenesis
Authors: Anna L. M. Smith, Julia C. Whitehall, Carla Bradshaw, David Gay, Fiona Robertson, Alasdair P. Blain, Gavin Hudson, Angela Pyle, David Houghton, Matthew Hunt, James N. Sampson, Craig Stamp, Grace Mallett, Shoba Amarnath, Jack Leslie, Fiona Oakley, Laura Wilson, Angela Baker, Oliver M. Russell, Riem Johnson, Claire A. Richardson, Bhavana Gupta, Iain McCallum, Stuart A. C. McDonald, Seamus Kelly, John C. Mathers, Rakesh Heer, Robert W. Taylor, Neil D. Perkins, Doug M. Turnbull, Owen J. Sansom, Laura C. Greaves
Journal: Nature Cancer (2020)
Proportion of Never Smokers Among Men and Women With Lung Cancer in 7 US States
Authors: David A. Siegel, Stacey A. Fedewa, S. Jane Henley, Lori A. Pollack, Ahmedin Jemal
Journal: JAMA Oncology (2020)

Proportion of Never Smokers Among Men and Women With Lung Cancer in 7 US StatesPrevious studies reported increases in the proportion of patients in the US and UK with lung cancer who never smoked cigarettes, 1,2 but these were based on small sample sizes from hospital data rather than population-based cancer registries.Beginning in 2011, the US Centers for Disease Control and Prevention (CDC) National Program of Cancer Registries supported a comparative effectiveness research project to abstract cigarette smoking history from the medical records of patients. 3Using these populationbased data, we examined cigarette smoking patterns by demographic and clinical characteristics among patients with lung cancer.
Dynamic Cardiolipin Synthesis Is Required for CD8+ T Cell Immunity
Authors: Mauro Corrado, Joy Edwards-Hicks, Matteo Villa, Lea J. Flachsmann, David E. Sanin, Maaike Jacobs, Francesc Baixauli, Michal Stanczak, Eve Anderson, Mai Azuma, Andrea Quintana, Jonathan D. Curtis, Thomas Clapes, Katarzyna M. Grzes, Agnieszka M. Kabat, Ryan Kyle, Annette E. Patterson, Ramon Klein Geltink, Borko Amulic, Colin G. Steward, Douglas Strathdee, Eirini Trompouki, David O’Sullivan, Edward J. Pearce, Erika L. Pearce
Journal: Cell Metabolism (2020)

Mitochondria constantly adapt to the metabolic needs of a cell. This mitochondrial plasticity is critical to T cells, which modulate metabolism depending on antigen-driven signals and environment. We show here that de novo synthesis of the mitochondrial membrane-specific lipid cardiolipin maintains CD8+ T cell function. T cells deficient for the cardiolipin-synthesizing enzyme PTPMT1 had reduced cardiolipin and responded poorly to antigen because basal cardiolipin levels were required for activation. However, neither de novo cardiolipin synthesis, nor its Tafazzin-dependent remodeling, was needed for T cell activation. In contrast, PTPMT1-dependent cardiolipin synthesis was vital when mitochondrial fitness was required, most notably during memory T cell differentiation or nutrient stress. We also found CD8+ T cell defects in a small cohort of patients with Barth syndrome, where TAFAZZIN is mutated, and in a Tafazzin-deficient mouse model. Thus, the dynamic regulation of a single mitochondrial lipid is crucial for CD8+ T cell immunity.
Inhaler technique knowledge and skills before and after an educational program in obstructive respiratory disease patients: A real-life pilot study
Authors: M. Vitacca, M. Paneroni, M. Fracassi, E. Mandora, L. Cerqui, G. Benedetti, C. Zanoni, A. Pluda, L. Bertacchini, D. Fiorenza
Journal: Pulmonology (2020)

Patients present poor knowledge and skills about their respiratory disease and inhaler device. We aimed to: (1) evaluate COPD and asthmatic patients... ability to manage inhaled drugs (2) identify differences among devices and (3) correlate clinical data with patient ability. Patients (n = 134) admitted for pulmonary rehabilitation (PR) were given an ad-hoc questionnaire covering 0% as the worst and 100% the best value of global ability (indicating the sum of knowledge and skills in managing inhaled drugs) at baseline (T0) and discharge (T1). Educational program was provided during PR. Setting of rehabilitation, age, sex, diagnosis, spirometry, CIRS score, level of autonomy to use medications, if na..ve about PR, educational level, and number/type of prescribed inhaled drugs were recorded. Most patients used 1 drug while 37% used 2 drugs. DPIs were the main device prescribed. At baseline, patients... mean level of knowledge and skills were 73% and 58%, respectively. There was a significant difference in level of skills (p = 0.046) among device families, DPIs resulting worst and pMDIs best. Global ability, skills and knowledge improved after educational support (p < 0.001) but did not reach the optimal level, 88%, 87% and 89%, respectively. Baseline global ability was positively correlated to female gender, younger age, previous PR access, outpatient status, higher education level and GOLD D class. At hospital admission, global ability was not optimal. Education may improve this, irrespective of the type of device used, in particular in male, elderly, na..ve to PR, low educational level patients.
2021 ACC/AHA/SVM/ACP Advanced Training Statement on Vascular Medicine (Revision of the 2004 ACC/ACP/SCAI/SVMB/SVS Clinical Competence Statement on Vascular Medicine and Catheter-Based Peripheral Vascular Interventions)
Authors: Mark A. Creager, Naomi M. Hamburg, Keith D. Calligaro, Ana I. Casanegra, Rosario Freeman, Phyllis A. Gordon, Heather L. Gornik, Esther S.H. Kim, Nicholas J. Leeper, Geno J. Merli, Khusrow Niazi, Jeffrey W. Olin, Rene Quiroz, Elona Rrapo Kaso, Suman Wasan, Andrew R. Waxler, Christopher J. White, Khendi White Solaru, Marlene S. Williams
Journal: Journal of the American College of Cardiology (2020)
Improving the trans-ancestry portability of polygenic risk scores by prioritizing variants in predicted cell-type-specific regulatory elements
Authors: Tiffany Amariuta, Kazuyoshi Ishigaki, Hiroki Sugishita, Tazro Ohta, Masaru Koido, Kushal K. Dey, Koichi Matsuda, Yoshinori Murakami, Alkes L. Price, Eiryo Kawakami, Chikashi Terao, Soumya Raychaudhuri
Journal: Nature Genetics (2020)
Optimizing the quality of clinical studies on oral microbiome: A practical guide for planning, performing, and reporting
Authors: Egija Zaura, Vincent Y. Pappalardo, Mark J. Buijs, Catherine M. C. Volgenant, Bernd W. Brandt
Journal: Periodontology 2000 (2020)

With this review, we aim to increase the quality standards for clinical studies with microbiome as an output parameter. We critically address the existing body of evidence for good quality practices in oral microbiome studies based on 16S rRNA gene amplicon sequencing. First, we discuss the usefulness of microbiome profile analyses. Is a microbiome study actually the best approach for answering the research question? This is followed by addressing the criteria for the most appropriate study design, sample size, and the necessary data (study metadata) that should be collected. Next, we evaluate the available evidence for best practices in sample collection, transport, storage, and DNA isolation. Finally, an overview of possible sequencing options (eg, 16S rRNA gene hypervariable regions, sequencing platforms), processing and data interpretation approaches, as well as requirements for meaningful data storage, sharing, and reporting are provided.
Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes
Authors: Chirag Nepal, Bin Zhu, Colm J. O’Rourke, Deepak Kumar Bhatt, Donghyuk Lee, Lei Song, Difei Wang, Alison L. Van Dyke, Hyoyoung Choo-Wosoba, Zhiwei Liu, Allan Hildesheim, Alisa M. Goldstein, Michael Dean, Juan LaFuente-Barquero, Scott Lawrence, Karun Mutreja, Mary E. Olanich, Justo Lorenzo Bermejo, Catterina Ferreccio, Juan Carlos Roa, Asif Rashid, Ann W. Hsing, Yu-Tang Gao, Stephen J. Chanock, Juan Carlos Araya, Jesper B. Andersen, Jill Koshiol
Journal: Journal of Hepatology (2020)
Testosterone Therapy in Women With Heart Failure: “Why Can't a Woman Be More Like a Man?”⁎⁎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: Paul W. Armstrong, Justin A. Ezekowitz
Journal: Journal of the American College of Cardiology (2010)
198TiP SPOTLIGHT: Phase III study of zolbetuximab + mFOLFOX6 versus placebo + mFOLFOX6 in first-line Claudin18.2⁺/HER2⁻ advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJ)
Authors: K. Shitara, S-E. Al-Batran, Y-J. Bang, D. Catenacci, P.C. Enzinger, D.H. Ilson, S. Kim, F. Lordick, M.A. Shah, E. van Cutsem, R-H. Xu, A. Arozullah, J.W. Park, J.A. Ajani
Journal: Annals of Oncology (2020)
Abstract 12658: Quantifying the Impact of Influenza on Cardiovascular Health Outcomes and Activity Among Persons With Type 2 Diabetes Mellitus
Authors: Sandrine Samson, Wei-Nchih Lee, Tom Quisel, Luca Foschini, Jan Liska, Henry Mills, Rosalind Hollingsworth, Michael Greenberg, Anne Beal
Journal: Circulation (2018)

Introduction: Diabetes independently increases the risks of poor outcomes from influenza and cardiovascular disease, yet the short term impact of influenza infection on daily activities and cardiov...
JAK Inhibition in the Aicardi–Goutières Syndrome
Authors: Laura Adang, Raphaela Goldbach-Mansky, Adeline Vanderver
Journal: New England Journal of Medicine (2020)

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Abstract S05-01: Profound CD8 T-cell responses towards SARS-CoV-2 OFR1ab in COVID-19 patients
Authors: Anastasia Gangaev, Steven L. Ketelaars, Sanne Patiwael, Anna Dopler, Olga I. Isaeva, Kelly Hoefakker, Sara De Biasi, Cristina Mussini, Giovanni Guaraldi, Massimo Girardis, Cami M.P. Talavera Ormeno, Paul J.M. Hekking, Neubury M. Lardy, Mireille Toebes, Robert Balderas, Ton N. Schumacher, Huib Ovaa, Andrea Cossarizza, Pia Kvistborg
Journal: Clinical Cancer Research (2020)

Abstract While there is accumulating evidence on the antibody response against SARS-CoV-2, we are only beginning to acquire knowledge regarding the SARS-CoV-2 specific CD8 T-cell response. Therefore, it is an urgent matter to gain a deeper insight into the virus specific CD8 T-cell response to both assist vaccine design and provide tools to evaluate the vaccine-induced T-cell responses. To address this issue, we have analyzed samples from 20 COVID-19 patients for CD8 T-cell recognition of 500 predicted SARS-CoV-2-derived epitopes restricted to 10 of the most common HLA-A and HLA-B alleles. For each HLA allele, the top 50 epitopes were selected based on predicted binding affinity and likelihood of successful proteasomal processing. In addition, SARS-CoV-2 epitope predictions shared by the science community were considered. To probe for CD8 T-cell recognition of the selected epitopes, we made use of our in-house technology based on multiplexing of peptide HLA (pHLA) multimers conjugated to fluorescent dyes. Our data demonstrated that CD8 T-cell reactivity against SARS-CoV-2 was common. Remarkably, a substantial fraction of the observed CD8 T-cell responses were directed towards the ORF1ab polyprotein 1ab. These CD8 T-cell responses were frequently of a profound magnitude. In particular, a CD8 T-cell response towards a potentially immunodominant epitope (TTDPSFLGRY) restricted to the HLA-A*01:01 allele was found in all patients positive for this allele. Interestingly, the fraction of SARS-CoV-2 specific CD8 T cells expressing the inhibitory receptor NKG2A was higher as compared to bulk CD8 T cells. In conclusion, the fact that a major part of the identified SARS-CoV-2 specific CD8 T-cell response is directed against a part of the viral genome that is not included in the majority of vaccine candidates currently in development may potentially influence their clinical activity and toxicity profile. Citation Format: Anastasia Gangaev, Steven L. Ketelaars, Sanne Patiwael, Anna Dopler, Olga I. Isaeva, Kelly Hoefakker, Sara De Biasi, Cristina Mussini, Giovanni Guaraldi, Massimo Girardis, Cami M.P. Talavera Ormeno, Paul J.M. Hekking, Neubury M. Lardy, Mireille Toebes, Robert Balderas, Ton N. Schumacher, Huib Ovaa, Andrea Cossarizza, Pia Kvistborg. Profound CD8 T-cell responses towards SARS-CoV-2 OFR1ab in COVID-19 patients [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 S05-01.
342P Comparison of 0.25 mg versus 0.75 mg of palonosetron in combination with aprepitant and dexamethasone for prevention of chemotherapy-induced nausea and vomiting following cisplatin-containing chemotherapy in patients with esophageal cancer
Authors: S. Horasawa, Y. Nakamura, S. Shimada, H. Taniguchi, T. Kojima, T. Aoyama, T. Yoshino
Journal: Annals of Oncology (2020)