tbuckley/cabot-search huggingface dataset:
Single-cell sequencing reveals antitumor characteristics of intratumoral immune cells in old mice
Authors: Cangang Zhang, Lei Lei, Xiaofeng Yang, Kaili Ma, Huiqiang Zheng, Yanhong Su, Anjun Jiao, Xin Wang, Haiyan Liu, Yujing Zou, Lin Shi, Xiaobo Zhou, Chenming Sun, Yuzhu Hou, Zhengtao Xiao, Lianjun Zhang, Baojun Zhang
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Aging has long been thought to be a major risk factor for various types of cancers. However, accumulating evidence indicates increased resistance of old animals to tumor growth. An in-depth understanding of how old individuals defend against tumor invasion requires further investigations. Methods We revealed age-associated alterations in tumor-infiltrating immune cells between young and old mice using single-cell RNA and coupled T cell receptor (TCR) sequencing analysis. Multiple bioinformatics methods were adopted to analyze the characteristics of the transcriptome between two groups. To explore the impacts of young and old CD8 + T cells on tumor growth, mice were treated with anti-CD8 antibody every 3 days starting 7 days after tumor inoculation. Flow cytometry was used to validate the differences indicated by sequencing analysis between young and old mice. Results We found a higher proportion of cytotoxic CD8 + T cells, naturally occurring Tregs, conventional dendritic cell (DC), and M1-like macrophages in tumors of old mice compared with a higher percentage of exhausted CD8 + T cells, induced Tregs, plasmacytoid DC, and M2-like macrophages in young mice. Importantly, TCR diversity analysis showed that top 10 TCR clones consisted primarily of exhausted CD8 + T cells in young mice whereas top clones were predominantly cytotoxic CD8 + T cells in old mice. Old mice had more CD8 + T cells with a ‘progenitor’ and less ‘terminally’ exhausted phenotypes than young mice. Consistently, trajectory inference demonstrated that CD8 + T cells preferentially differentiated into cytotoxic cells in old mice in contrast to exhausted cells in young mice. Importantly, elimination of CD8 + T cells in old mice during tumor growth significantly accelerated tumor development. Moreover, senescent features were demonstrated in exhausted but not cytotoxic CD8 + T cells regardless of young and old mice. Conclusions Our data revealed that a significantly higher proportion of effector immune cells in old mice defends against tumor progression, providing insights into understanding the altered kinetics of cancer development and the differential response to immunotherapeutic modulation in elderly patients.
Identification of the therapeutic window for use of steroids in severe alcoholic hepatitis: a large global study
Authors: Juan Pablo Arab, Natalia Baeza, Luis Antonio Diaz, Francisco Javier Idalsoaga, Dalia Morales Arraez, Meritxell Ventura-Cots, Wei Zhang, Joseph Ahn, Douglas A. Simonetto, Tej Mehta, Horia Stefanescu, Adelina Horhat, Andreea Bumbu, Winston Dunn, Bashar M. Attar, Rohit Agrawal, Joaquin Cabezas, Richard Parker, Maria Poca Sans, German Soriano Pastor, Shiv Kumar Sarin, Rakhi Maiwall, Prasun K. Jalal, Saba Abdulsada, Maria Higuera De La Tijera, Anand V. Kulkarni, Patricia Guerra Salazar, Lubomir Skladany, Natalia Bystrianska, Veronica Enith Prado Gonzalez, Ana Clemente, Diego Rincon, Tehseen Haider, Fernando Cairo, Marcela De Sousa Cohelo, Gustavo Romero, Florencia Pollarsky, Juan Carlos Restrepo, Luis Guillermo Toro Rendon, Pamela Yaquich, Manuel Mendizabal, Maria Laura Garrido, Sebastian Marciano, Fernando Oscar Bessone, Julio Santiago Marcelo, Diego Piombino, Melisa Dirchwolf, Juan Pablo Arancibia, Jose Altamirano, Won Kim, Roberta C. Araujo, Andres Duarte-Rojo, Victor M. Vargas Blasco, Pierre-Emmanuel Rautou, Felipe Zamarripa, Aldo Torre, Michael R. Lucey, Philippe Mathurin, Guadalupe Garcia-Tsao, Jose Alberto Gonzalez, Betsy C. Verna, Robert S. Brown, Juan Roblero Cum, Juan G. Abraldes, Marco Arrese, Vijay Shah, Patrick S. Kamath, Ashwani K. Singal, Ramon Bataller
Journal: Hepatology (2020)
Chemoresistance phenotype in human ovarian carcinoma cells induced by chronic erythropoietin treatment in vitro
Authors: Peter Solar, Laurie Feldman, Arthur J. Sytkowski
Journal: Cancer Research (2004)

1216  Recombinant human erythropoietin (Epo) is widely used to treat anemia associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinum-based regimens. The anti-apoptotic and proliferative affects of Epo, in both hematopoietic and non-hematopoietic cells, are well established. Additionally, various studies –including our own–have demonstrated that the growth of some tumor cells may be stimulated directly by Epo. In the current investigation, we found that chronically Epo-treated (> 2 months) A2780 human ovarian adenocarcinoma cells exhibited significantly greater survival following in vitro paclitaxel treatment than did non-Epo-treated A2780 cells, and the quantity of apoptotic products (mono- and oligonucleosomes) was lower in Epo-treated than in non-Epo-treated cells after paclitaxel. Flow cytometry analysis detected reduced numbers of Epo-treated cells in G2 phase and increased numbers of cells in S phase of the cell cycle in comparison to control cells following paclitaxel treatment. Paradoxically, western blotting demonstrated down-regulation of Bcl-2 in chronically Epo-treated cells. Comparative Affymetrix GeneChip expression analysis (MAS 5.0 algorithm) showed increased expression of several genes in Epo-treated A2780 cells potentially involved in the chemoresistance phenotype in comparison to non-Epo-treated cells. Several other genes were underexpressed in Epo-treated cells. The differential expression of selected genes was confirmed by real-time PCR, thus validating the expression analysis. These results may have important implications for ovarian cancer patients undergoing paclitaxel treatment and receiving Epo.
Maria Helena Gilleece
Authors: Anne Robinson, Rod Johnson, Mark Hughes
Journal: BMJ (2021)

Maria Helena Gilleece was a distinguished and talented student, attaining scholarships, winning the Henry Cohen and W.F Jones year prizes in medicine and general practice, and intercalating with a BSc honours in biochemistry. She was a keen member of the renowned Liverpool Medical Students Society and, in her capacity as its secretary, edited their long running publication “Sphincter.”

A keen interest in haematology was apparent from an early stage and on completing general medical training, Maria took a post as a haematology registrar at the Royal Liverpool Hospital in 1989. She moved on to Manchester’s Paterson Research Institute (now the CRUK-MI) for four years, firstly as the Joseph Starkey research fellow and then as a Leukaemia Research Fund clinical fellow. She then remained in the north west as a senior registrar, completing her specialty training and submitting her MD thesis.

In 1997, she left British shores to take up a two year Kay Kendall Leukaemia Fund fellowship …
Interruption of neutrophil extracellular traps formation dictates host defense and tubular HOXA5 stability to augment efficacy of anti-Fn14 therapy against septic AKI
Authors: Yin Ni, Bang-Chuan Hu, Guo-Hua Wu, Zi-Qiang Shao, Yang Zheng, Run Zhang, Jun Jin, Jun Hong, Xiang-Hong Yang, Ren-Hua Sun, Jin-Quan Liu, Shi-Jing Mo
Journal: Theranostics (2021)

The immunosuppressive, inflammatory microenvironment orchestrated by neutrophil extracellular traps (NETs) plays a principal role in pathogenesis of sepsis. Fibroblast growth factor-inducible molecule 14 (Fn14) has been established as a potential target for septic acute kidney injury (AKI), making further therapeutic benefits from combined NETs and Fn14 blockade possible.
OA10.04 COVID-19 Vaccine Acceptance and Communications Effectiveness Amongst Canadian Lung Cancer Patients.
Authors: C. Sit, I. Effiong, M. Bradley, A.M. Cerato, H. Hogan, T. Monds, A. Pratt, A. Redway, C. Qiong Wu
Journal: Journal of Thoracic Oncology (2021)
MA10.02 Lung Cancer Detected By Screening, Incidental Lung Nodule Program and Neither: A Prospective Observational Study
Authors: R. Osarogiagbon, W. Liao, N. Faris, M. Smeltzer, M. Meadows-Taylor, M. Ray, C. Fehnel, J. Goss, S. Williams, O. Akinbobola, A. Pacheco, A. Epperson, J. Luttrell, D. Mccoy, P. Lammers, A. Bishop, K. Tonkin, R. Optican, J. Wright, T. Robbins
Journal: Journal of Thoracic Oncology (2021)
Cranial Meningiomas Requiring Cranioplasty
Authors: Max Norrington, Christopher Millward, John Doherty, Mohammad Mustafa, Thomas Humphries, Conor Gillespie, George Richardson, Abdurrahman Islim, Michael Jenkinson, Andrew Brodbelt
Journal: Neuro-Oncology (2021)

Abstract Aims Bone infiltration in association with intracranial meningioma (4.5% of cases) and primary intraosseous meningioma (2%) are rare. Management can be challenging, as cranial vault reconstruction may be required. This study aimed to examine the surgical techniques used and outcomes in this patient population. Method A single-centre, retrospective cohort study was conducted between January 2010 and September 2020. All adult patients who required cranial reconstruction due to bone involvement of their meningioma were included. Patient demographics, tumour characteristics, operative details, complications, and outcomes were examined. Statistical analyses were performed using SPSS v24.0. Results There were 30 patients (17 female; 56.7%), median age 54 yrs (range 28-86 yrs), of whom 25 (83.3%) had bone infiltration, and 5 (16.7%) had primary intraosseous meningioma. Only 10 patients had a Simpson I or II resection. Twenty-eight had 'on-table' primary cranioplasties. Materials used were titanium (n=13; 43.3%), acrylic (n=10; 33.3%), PMMA (n=5; 16.7%), and hydroxyapatite (n=2; 6.7%). There were 9 (mostly minor) surgical complications and only one wound infection. Twelve patients had WHO grade II tumours, and 14 required radiotherapy. Ten patients (33.3%) had re-operation for recurrent tumour, with a median time to progression of 41 months. At 6 months, 24 patients had a performance score less than 2. Conclusion On-table cranioplasty provides a lower risk surgical option for patients with high risk meningiomas.
간섬유화의 비침습적 진단: transient elastography (FibroScan(R))
Authors: 김승업
Journal: Clinical and Molecular Hepatology (2011)

Transient elastography (TE, FibroScan(R)) is a novel non-invasive method that has been proposed for the assessment of liver fibrosis in patients with chronic liver diseases, by measuring liver stiffness. TE is a rapid and user-friendly technique that can be easily performed at the bedside or in the outpatient clinic with immediate results and good reproducibility. Combining TE with serum markers increases diagnostic accuracy and as a result, liver biopsy could be avoided for initial assessment in some patients with chronic liver disease. As TE has excellent patient acceptance it could be useful for monitoring fibrosis progression and regression in the individual case, but more data are awaited for this application. Guidelines are needed for the use of TE in clinical practice.
Mutations and variants of ONECUT1 in diabetes
Authors: Anne Philippi, Sandra Heller, Ivan G. Costa, Valérie Senée, Markus Breunig, Zhijian Li, Gino Kwon, Ronan Russell, Anett Illing, Qiong Lin, Meike Hohwieler, Anne Degavre, Pierre Zalloua, Stefan Liebau, Michael Schuster, Johannes Krumm, Xi Zhang, Ryan Geusz, Jacqueline R. Benthuysen, Allen Wang, Joshua Chiou, Kyle Gaulton, Heike Neubauer, Eric Simon, Thomas Klein, Martin Wagner, Gopika Nair, Céline Besse, Claire Dandine-Roulland, Robert Olaso, Jean-François Deleuze, Bernhard Kuster, Matthias Hebrok, Thomas Seufferlein, Maike Sander, Bernhard O. Boehm, Franz Oswald, Marc Nicolino, Cécile Julier, Alexander Kleger
Journal: Nature Medicine (2021)
Assessment of Omecamtiv Mecarbil for the Treatment of Patients With Severe Heart Failure
Authors: G. Michael Felker, Scott D. Solomon, Brian Claggett, Rafael Diaz, John J. V. McMurray, Marco Metra, Inder Anand, Marisa G. Crespo-Leiro, Ulf Dahlström, Eva Goncalvesova, Jonathan G. Howlett, Peter MacDonald, Alexander Parkhomenko, János Tomcsányi, Siddique A. Abbasi, Stephen B. Heitner, Thomas Hucko, Stuart Kupfer, Fady I. Malik, John R. Teerlink
Journal: JAMA Cardiology (2021)

Heart failure with reduced ejection fraction is a progressive clinical syndrome, and many patients' condition worsen over time despite treatment. Patients with more severe disease are often intolerant of available medical therapies.
Management and Outcomes of Diffuse Large B-cell Lymphoma Post-transplant Lymphoproliferative Disorder in the Era of PET and Rituximab: A Multicenter Study From the Australasian Lymphoma Alliance
Authors: Stephen Boyle, Joshua W. D. Tobin, Jacinta Perram, Nada Hamad, Veena Gullapalli, Allison Barraclough, Lydia Singaraveloo, Min-Hi Han, Richard Blennerhassett, Niles Nelson, Anna M. Johnston, Dipti Talaulikar, Krishna Karpe, Abir Bhattacharyya, Chan Yoon Cheah, Elango Subramoniapillai, Waqas Bokhari, Cindy Lee, Eliza A. Hawkes, Andrew Jabbour, Simone I. Strasser, Steven J. Chadban, Christina Brown, Peter Mollee, Greg Hapgood
Journal: HemaSphere (2021)

There are limited data on post-transplant lymphoproliferative disorder (PTLD) in the era of positron emission tomography (PET) and rituximab (R). Furthermore, there is limited data on the risk of graft rejection with modern practices in reduction in immunosuppression (RIS). We studied 91 patients with monomorphic diffuse large B-cell lymphoma PTLD at 11 Australian centers: median age 52 years, diagnosed between 2004 and 2017, median follow-up 4.7 years (range, 0.5-14.5 y). RIS occurred in 88% of patients. For patients initially treated with R-monotherapy, 45% achieved complete remission, rising to 71% with the addition of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP) for those not in complete remission. For patients initially treated with R-CHOP, the complete remission rate was 76%. There was no difference in overall survival (OS) between R-monotherapy and R-chemotherapy patients. There was no difference in OS for patients with systemic lymphoma (n = 68) versus central nervous system (CNS) involvement (n = 23) (3-y OS 72% versus 73%; P = 0.78). Treatment-related mortality was 7%. End of treatment PET was prognostic for patients with systemic lymphoma with longer OS in the PET negative group (3-y OS 91% versus 57%; P = 0.01). Graft rejection occurred in 9% (n = 4 biopsy-proven; n = 4 suspected) during the entire follow-up period with no cases of graft loss. RIS and R-based treatments are safe and effective with a low likelihood of graft rejection and high cure rate for patients achieving complete remission with CNS or systemic PTLD.
P47.13 First-in-Human, Dose Escalation and Expansion Study of MT-6402 in Patients With PD-L1 Expressing Advanced Solid Tumors
Authors: D.R. Spigel, B. Anand, K. Carroll, J. Dekker, A. Georgy, S. Hankins, A. Rethy
Journal: Journal of Thoracic Oncology (2021)
Vessel-CAPTCHA: An efficient learning framework for vessel annotation and segmentation
Authors: Vien Ngoc Dang, Francesco Galati, Rosa Cortese, Giuseppe Di Giacomo, Viola Marconetto, Prateek Mathur, Karim Lekadir, Marco Lorenzi, Ferran Prados, Maria A. Zuluaga
Journal: Medical Image Analysis (2021)

Deep learning techniques for 3D brain vessel image segmentation have not been as successful as in the segmentation of other organs and tissues. This can be explained by two factors. First, deep learning techniques tend to show poor performances at the segmentation of relatively small objects compared to the size of the full image. Second, due to the complexity of vascular trees and the small size of vessels, it is challenging to obtain the amount of annotated training data typically needed by deep learning methods. To address these problems, we propose a novel annotation-efficient deep learning vessel segmentation framework. The framework avoids pixel-wise annotations, only requiring weak patch-level labels to discriminate between vessel and non-vessel 2D patches in the training set, in a setup similar to the CAPTCHAs used to differentiate humans from bots in web applications. The user-provided weak annotations are used for two tasks: 1) to synthesize pixel-wise pseudo-labels for vessels and background in each patch, which are used to train a segmentation network, and 2) to train a classifier network. The classifier network allows to generate additional weak patch labels, further reducing the annotation burden, and it acts as a noise filter for poor quality images. We use this framework for the segmentation of the cerebrovascular tree in Time-of-Flight angiography (TOF) and Susceptibility-Weighted Images (SWI). The results show that the framework achieves state-of-the-art accuracy, while reducing the annotation time by ~77% w.r.t. learning-based segmentation methods using pixel-wise labels for training.
P64.01 The Canadian Small Cell Lung Cancer Database (CASCaDe): A Multi-Institutional Real-World Evidence Collaboration
Authors: S. Moore, J. Agulnik, G. Bebb, D. Dawe, A. Elegbede, A. Fung, C. Ho, G. Liu, B. Lok, S. Snow, P. Wheatley-Price
Journal: Journal of Thoracic Oncology (2021)
CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial
Authors: Shaun Cordoba, Shimobi Onuoha, Simon Thomas, Daniela Soriano Pignataro, Rachael Hough, Sara Ghorashian, Ajay Vora, Denise Bonney, Paul Veys, Kanchan Rao, Giovanna Lucchini, Robert Chiesa, Jan Chu, Liz Clark, Mei Mei Fung, Koval Smith, Carlotta Peticone, Muhammad Al-Hajj, Vania Baldan, Mathieu Ferrari, Saket Srivastava, Ram Jha, Frederick Arce Vargas, Kevin Duffy, William Day, Paul Virgo, Lucy Wheeler, Jeremy Hancock, Farzin Farzaneh, Sabine Domning, Yiyun Zhang, Nushmia Z. Khokhar, Vijay G. R. Peddareddigari, Robert Wynn, Martin Pule, Persis J. Amrolia
Journal: Nature Medicine (2021)

Abstract Chimeric antigen receptor (CAR) T cells targeting CD19 or CD22 have shown remarkable activity in B cell acute lymphoblastic leukemia (B-ALL). The major cause of treatment failure is antigen downregulation or loss. Dual antigen targeting could potentially prevent this, but the clinical safety and efficacy of CAR T cells targeting both CD19 and CD22 remain unclear. We conducted a phase 1 trial in pediatric and young adult patients with relapsed or refractory B-ALL ( n = 15) to test AUTO3, autologous transduced T cells expressing both anti-CD19 and anti-CD22 CARs (AMELIA trial, EUDRA CT 2016-004680-39). The primary endpoints were the incidence of grade 3–5 toxicity in the dose-limiting toxicity period and the frequency of dose-limiting toxicities. Secondary endpoints included the rate of morphological remission (complete response or complete response with incomplete bone marrow recovery) with minimal residual disease-negative response, as well as the frequency and severity of adverse events, expansion and persistence of AUTO3, duration of B cell aplasia, and overall and event-free survival. The study endpoints were met. AUTO3 showed a favorable safety profile, with no dose-limiting toxicities or cases of AUTO3-related severe cytokine release syndrome or neurotoxicity reported. At 1 month after treatment the remission rate (that is, complete response or complete response with incomplete bone marrow recovery) was 86% (13 of 15 patients). The 1 year overall and event-free survival rates were 60% and 32%, respectively. Relapses were probably due to limited long-term AUTO3 persistence. Strategies to improve CAR T cell persistence are needed to fully realize the potential of dual targeting CAR T cell therapy in B-ALL.
Effect of dietary sources of calcium and protein on hip fractures and falls in older adults in residential care: cluster randomised controlled trial
Authors: S Iuliano, S Poon, J Robbins, M Bui, X Wang, L De Groot, M Van Loan, A Ghasem Zadeh, T Nguyen, E Seeman
Journal: BMJ (2021)

To assess the antifracture efficacy and safety of a nutritional intervention in institutionalised older adults replete in vitamin D but with mean intakes of 600 mg/day calcium and <1 g/kg body weight protein/day.Two year cluster randomised controlled trial.60 accredited residential aged care facilities in Australia housing predominantly ambulant residents.7195 permanent residents (4920 (68%) female; mean age 86.0 (SD 8.2) years).Facilities were stratified by location and organisation, with 30 facilities randomised to provide residents with additional milk, yoghurt, and cheese that contained 562 (166) mg/day calcium and 12 (6) g/day protein achieving a total intake of 1142 (353) mg calcium/day and 69 (15) g/day protein (1.1 g/kg body weight). The 30 control facilities maintained their usual menus, with residents consuming 700 (247) mg/day calcium and 58 (14) g/day protein (0.9 g/kg body weight).Group differences in incidence of fractures, falls, and all cause mortality.Data from 27 intervention facilities and 29 control facilities were analysed. A total of 324 fractures (135 hip fractures), 4302 falls, and 1974 deaths were observed. The intervention was associated with risk reductions of 33% for all fractures (121 v 203; hazard ratio 0.67, 95% confidence interval 0.48 to 0.93; P=0.02), 46% for hip fractures (42 v 93; 0.54, 0.35 to 0.83; P=0.005), and 11% for falls (1879 v 2423; 0.89, 0.78 to 0.98; P=0.04). The risk reduction for hip fractures and falls achieved significance at five months (P=0.02) and three months (P=0.004), respectively. Mortality was unchanged (900 v 1074; hazard ratio 1.01, 0.43 to 3.08).Improving calcium and protein intakes by using dairy foods is a readily accessible intervention that reduces the risk of falls and fractures commonly occurring in aged care residents.Australian New Zealand Clinical Trials Registry ACTRN12613000228785.