tbuckley/cabot-search huggingface dataset:
The impact of the temporary suspension of national cancer screening programmes due to the COVID-19 epidemic on the diagnosis of breast and colorectal cancer in the Netherlands
Authors: Avinash G. Dinmohamed, Matteo Cellamare, Otto Visser, Linda de Munck, Marloes A. G. Elferink, Pieter J. Westenend, Jelle Wesseling, Mireille J. M. Broeders, Ernst J. Kuipers, Matthias A. W. Merkx, Iris D. Nagtegaal, Sabine Siesling
Journal: Journal of Hematology & Oncology (2020)

Oncological care was largely derailed due to the reprioritisation of health care services to handle the initial surge of COVID-19 patients adequately. Cancer screening programmes were no exception in this reprioritisation. They were temporarily halted in the Netherlands (1) to alleviate the pressure on health care services overwhelmed by the upsurge of COVID-19 patients, (2) to reallocate staff and personal protective equipment to support critical COVID-19 care, and (3) to mitigate the spread of COVID-19. Utilising data from the Netherlands Cancer Registry on provisional cancer diagnoses between 6 January 2020 and 4 October 2020, we assessed the impact of the temporary halt of national population screening programmes on the diagnosis of breast and colorectal cancer in the Netherlands. A dynamic harmonic regression model with ARIMA error components was applied to assess the observed versus expected number of cancer diagnoses per calendar week. Fewer diagnoses of breast and colorectal cancer were objectified amid the early stages of the initial COVID-19 outbreak in the Netherlands. This effect was most pronounced among the age groups eligible for cancer screening programmes, especially in breast cancer (age group 50–74 years). Encouragingly enough, the observed number of diagnoses ultimately reached and virtually remained at the level of the expected values. This finding, which emerged earlier in age groups not invited for cancer screening programmes, comes on account of the decreased demand for critical COVID-19 care since early April 2020, which, in turn, paved the way forward to resume screening programmes and a broad range of non-critical health care services, albeit with limited operating and workforce capacity. Collectively, transient changes in health-seeking behaviour, referral practices, and cancer screening programmes amid the early stages of the initial COVID-19 epidemic in the Netherlands conjointly acted as an accelerant for fewer breast and colorectal cancer diagnoses in age groups eligible for cancer screening programmes. Forthcoming research is warranted to assess whether the decreased diagnostic scrutiny of cancer during the COVID-19 pandemic resulted in stage migration and altered clinical management, as well as poorer outcomes.
Endogenous HLA-DQ8αβ programs superantigens (SEG/SEI) to silence toxicity and unleash a tumoricidal network with long-term melanoma survival
Authors: Peter Knopick, David Terman, Nathan Riha, Travis Alvine, Riley Larson, Cedric Badiou, Gerard Lina, John Ballantyne, David Bradley
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background As the most powerful T cell agonists known, superantigens (SAgs) have enormous potential for cancer immunotherapy. Their development has languished due to high incidence (60%–80%) of seroreactive neutralizing antibodies in humans and tumor necrosis factor-α (TNFα)-mediated cardiopulmonary toxicity. Such toxicity has narrowed their therapeutic index while neutralizing antibodies have nullified their therapeutic effects. Methods Female HLA-DQ8 (DQA*0301/DQB*0302) tg mice expressing the human major histocompatibility complex II (MHCII) HLA-DQ8 allele on a high proportion of PBL, spleen and lymph node cells were used. In the established tumor model, staphylococcal enterotoxin G and staphylococcal enterotoxin I (SEG/ SEI) (50 µg each) were injected on days 6 and 9 following tumor inoculation. Lymphoid, myeloid cells and tumor cell digests from tumor tissue were assayed using flow cytometry or quantitated using a cytometric bead array. Tumor density, necrotic and viable areas were quantitated using the ImageJ software. Results In a discovery-driven effort to address these problems we introduce a heretofore unrecognized binary complex comprizing SEG/SEI SAgs linked to the endogenous human MHCII HLA-DQ8 allele in humanized mice. By contrast to staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) deployed previously in clinical trials, SEG and SEI does not exhibit neutralizing antibodies in humans or TNFα-mediated toxicity in humanized HLA-DQ8 mice. In the latter model wherein SAg behavior is known to be ‘human-like’, SEG/SEI induced a powerful tumoricidal response and long-term survival against established melanoma in 82% of mice. Other SAgs deployed in the same model displayed toxic shock. Initially, HLA-DQ8 mediated melanoma antigen priming, after which SEG/SEI unleashed a broad CD4+ and CD8+ antitumor network marked by expansion of melanoma reactive T cells and interferon-γ (IFNy) in the tumor microenvironment (TME). SEG/SEI further initiated chemotactic recruitment of tumor reactive T cells to the TME converting the tumor from ‘cold’ to a ‘hot’. Long-term survivors displayed remarkable resistance to parental tumor rechallenge along with the appearance of tumor specific memory and tumor reactive T memory cells. Conclusions Collectively, these findings show for the first time that the SEG/SEI-(HLA-DQ8) empowers priming, expansion and recruitment of a population of tumor reactive T cells culminating in tumor specific memory and long-term survival devoid of toxicity. These properties distinguish SEG/SEI from other SAgs used previously in human tumor immunotherapy. Consolidation of these principles within the SEG/SEI-(HLA-DQ8) complex constitutes a conceptually new therapeutic weapon with compelling translational potential.
Preferential Usage of Specific Immunoglobulin Heavy Chain Variable Region Genes with Unmutated Profile and Advanced Stage at Presentation Are Common Features in Patients with Chronic Lymphocytic Leukemia from Senegal
Authors: Abibatou Sall, Teresa Amato, Alessandro Gozzetti, Awa Oumar Touré, Saliou Diop, Lorenzo Leoncini, Pier Paolo Piccaluga, Martine Raphaël
Journal: Blood (2020)
The Comparison of Novel Oral Anticoagulants with Conventional Anticoagulants in the Treatment of Cancer-Associated Thrombosis: A Systemic Review
Authors: Muhammad Tayyeb, Syed Maaz Abdullah, Ali Jaan, Muhammad Khawar Sana, Ahsan Wahab, Sundas Ali, Farhan Khalid, Hamid Ehsan, Sobia Aamir, Saad Javed, Aamir Shahzad, Faiz Anwer
Journal: Blood (2020)
Protective-2 (BPI-2358-106): A Confirmatory Trial to Demonstrate Superiority of the Plinabulin+Pegfilgrastim (Plin/Peg) Combination Versus Standard of Care Pegfilgrastim for the Prevention of Chemotherapy-Induced Neutropenia (CIN) in Breast Cancer (BC) Patients (pts)
Authors: Douglas W. Blayney, Ramon Mohanlal, Lan Huang
Journal: Blood (2020)
Allogeneic Hematopoietic Cell Transplantation in Patients with Therapy-Related Myeloid Neoplasm after Breast Cancer: A Study of the Chronic Malignancies Working Party of the EBMT
Authors: Mitja Nabergoj, Katya Mauff, Dietrich W. Beelen, Arnold Ganser, Nicolaus Kröger, Martin Bornhäuser, Jürgen Finke, Jakob R. Passweg, Jan J. Cornelissen, Natalie Schub, Hendrik Veelken, Yves Beguin, Keith Wilson, Tsila Zuckerman, Aurelien Giltat, Celestine Simand, Rocio Parody, Pascal Turlure, Tessa Kerre, Linda Koster, Patrick J Hayden, Francesco Onida, Christof Scheid, Yves Chalandon, Marie Robin, Ibrahim Yakoub-Agha
Journal: Blood (2020)
Multiple Myeloma Multicenter Registry in Colombia: The Impact of Autologous Stem Transplantation on Overall and Disease-Free Survival
Authors: Virginia Abello, Claudia Lucia Sossa, Henry Idrobo, Guillermo Quintero, William Mantilla, Kenny Galvez, Alicia Henao-Uribe, Rigoberto Gomez, Domingo Saavedra, Lina Gaviria, Jheremy Enrique Reyes Castellanos, Monica Osuna Pérez, Juan Manuel Herrera
Journal: Blood (2020)
Phosphoproteomics Uncovers Synergy between DNA-PK and FLT3 Inhibitors in Acute Myeloid Leukaemia
Authors: Heather Murray, Anoop Kumar Enjeti, Richard Kahl, Hayley Flanagan, David Skerrett-Byrne, Juhura Al-Mazi, Nathan Smith, Charles de Bock, Martin Larsen, Nicole Verrills*, Matthew Dun*
Journal: Blood (2020)
Phase Ib Trial with Dose Expansion of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination with Rituximab and Lenalidomide in Patients with Refractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL) and Refractory/Recurrent Secondary Central Nervous System Lymphoma (SCNSL)
Authors: Christian Grommes, Anna Piotrowski, Elena Pentsova, Craig Nolan, Jasmine Francis, Lisa DeAngelis, Lauren Schaff, Ingo K Mellinghoff
Journal: Blood (2020)
Clinical Outcomes in Patients with Relapsed/Refractory Acute Myeloid Leukemia Treated with Gilteritinib Who Received Prior Midostaurin or Sorafenib
Authors: Alexander E. Perl, Jessica K. Altman, Naoko Hosono, Pau Montesinos, Nikolai A. Podoltsev, Giovanni Martinelli, Catherine C. Smith, Mark Levis, Christoph Röllig, Marco Groß-Langenhoff, Nahla Hasabou, Qiaoyang Lu, Ramon V. Tiu
Journal: Blood (2020)
Corticosteroid treatment in severe COVID-19 patients with acute respiratory distress syndrome
Authors: Jiao Liu, Sheng Zhang, Xuan Dong, Zhongyi Li, Qianghong Xu, Huibin Feng, Jing Cai, Sisi Huang, Jun Guo, Lidi Zhang, Yizhu Chen, Wei Zhu, Hangxiang Du, Yongan Liu, Tao Wang, Limin Chen, Zhenliang Wen, Djillali Annane, Jieming Qu, Dechang Chen
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. Corticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.
Outcomes of Chronic Myelomonocytic Leukemia (CMML) after Hypomethylating Agent (HMA) Failure
Authors: Veronia Guerra, Jorge M. Ramos Perez, Danielle Hammond, Kelly S. Chien, Rashmi Kanagal-Shamanna, Kiran Naqvi, Koji Sasaki, Shilpa Paul, Tapan M. Kadia, Courtney D. DiNardo, Marina Konopleva, Naval Daver, Farhad Ravandi, Naveen Pemmaraju, Nicholas J. Short, Ghayas C. Issa, Koichi Takahashi, Zeev E. Estrov, Sherry A. Pierce, Hagop M. Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban Bravo
Journal: Blood (2020)
Mary Baines: community palliative care pioneer
Authors: John Illman
Journal: BMJ (2020)

Mary Baines and a patient at St Christopher’s Hospice

Credit: Derek Bayes

One day in the mid-1960s Mary Baines heard a radio appeal for a hospice by Cicely Saunders, whom she had met in the Christian Union at St Thomas’ Hospital, London, in 1954. Baines sent her old friend a cheque for £3, even though she thought Saunders’s proposal “very odd.”

In 2014, Baines recalled, “Doctors, at this time, had no interest in people who were dying. They were only interested in people who could be cured. If you’d asked me whether I thought anything would have come of it, I would have said no. If you think of it, it is incredible. Can you think of any woman, or any man for that matter, who founded not only a hospice, but a branch of medicine around the world?”

Seeing that Baines worked near Saunders’s proposed hospice in Sydenham, south London, Saunders asked her to join the fledgling St Christopher’s team. It is easy to see why. Baines’s many qualities included two rarely found in any one person. She was empathetic and had a formidable analytical brain—one of the few women in the 1950s …
Abstract 15956: Under-Reporting and Under-Representation of Racial/Ethnic Minorities in Major Atrial Fibrillation Clinical Trials
Authors: Ashish Sarraju, David J Maron, Fatima Rodriguez
Journal: Circulation (2019)

Introduction: Atrial fibrillation is a major cause of morbidity and mortality in the United States. Ensuring racial/ethnic diversity in clinical trial participation is vital for generalizability of...
A Synthetic Lethal Approach to Eradicate AML Via Synergistic Activation of Pro-Apoptotic p53 By MDM2 and BET Inhibitors
Authors: Sha Li, Anne-Louise Latif, Ashley Newcombe, Kathryn Gilrory, Neil Robertson, Xue Lei, Darren Finlay, Karina Barbosa, Helen Stewart, John Cole, Maria Terradas Terradas, Loveena Rishi Delori, Lynn McGarry, Claire McKeeve, Claire Reid, William Clark, Joana Campos, Kristina Kirschner, Andrew Davis, Jonathan Lopez, Jun-Ichi Sakamaki, Jennifer Morton, Kevin Ryan, Stephen Tait, Sheela Abraham, Tessa L. Holyoake, Brian Higgins, Xu Huang, Karen Blyth, Mhairi Copland, Timothy Chevassut, Aniruddha J. Deshpande, Karen Keeshan, Peter Adams
Journal: Blood (2020)
Salicylates Potentiate and Broaden CRM1 Inhibitor Anti-Tumor Activity Via S-Phase Arrest and Impaired DNA-Damage Repair
Authors: Jithma P. Abeykoon, Xiaosheng Wu, Kevin E. Nowakowski, Surendra Dasari, Jonas Paludo, S. John Weroha, Chunling Hu, Jann Sarkaria, Ann Mladek, Jessica Phillips, Andrew L. Feldman, Aishwarya Ravindran, Rebecca L. King, Mary J. Stenson, Michelle Manske, Fergus Couch, Mrinal M. Patnaik, Thomas E. Witzig
Journal: Blood (2020)
Psychological Distress in Young Adults with Acute Myeloid Leukemia Undergoing Induction Chemotherapy
Authors: Bethany Lockwood, Areej El-Jawahri, Alison R. Walker, Deborah Russell, Jillian Gustin, Sarah Ehrman, Seuli Bose-Brill, Maryam Lustberg, Bhavana Bhatnagar
Journal: Blood (2020)
Brazilian Real-World Multiple Myeloma (MM) Electronic Platform Register Project
Authors: Edvan De Queiroz Crusoe, Glaciano Ribeiro, Karla Richter Zanella, Leila Martins Perobelli, Milton A. F. Aranha, Marcelo Capra, Roberto José Pessoa Magalhães, James Maciel, Rosane Bittencourt, Emanuella Souza, Rafael Dezen Gaiolla, Walter Braga, Fabiana Higashi, Gracia Martinez, Abrahão Elias Hallack Neto, Danielle Leao Cordeiro De Farias, Virgilio Costa Farnese, Nelson S Castro, Renato Tavares, Jacqueline Holanda De Souza, Jandey Glória Bigonha, Ederson Roberto Mattos, Caroline Sola, Joao Tadeu Souto Filho, LUiza da Silva, Cleder Aparecido Da Silva Da Silva Araujo, Jorge Vaz Pinto Neto, Emanuel Silva, Nelson Hamerschlak, Fabio Moore Nucci, Eduardo Flavio Oliveira Ribeiro, Rafael Cunha, Andre H Crepaldi, Manuella Sampaio Almeida, Gislaine B O Duarte, Andre Magalhaes, Dani Laks, Marcos Daniel, Angelo Maiolino, Vania T. M. Hungria
Journal: Blood (2020)
Correspondence on ‘The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease’
Authors: Rory James Redmond Peters, Harry Martin, Aleena Virdee, Eve Fryer, Helen Bungay, Manuel Rodriguez-Justo, Manil Chouhan, Eleanor Barnes, George Webster, Emma L Culver
Journal: Annals of the Rheumatic Diseases (2020)

IgG4-related disease (IgG4-RD) is a multisystem fibroinflammatory disorder diagnosed and managed across a broad spectrum of specialities. The American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for IgG4-RD, recently published in this journal,1 provide robust and validated measures for discrimination from disease mimics with excellent test performance. The classification criteria incorporates three domains: entry, exclusion and inclusion criteria, with numerically weighted inclusion criteria reaching a score of 20 points or more to support a diagnosis of IgG4-RD. We sought to evaluate these criteria in a real-world cohort of patients referred for discussion to our supraregional UK IgG4-RD multidisciplinary meeting (MDM) over a 3-year period from 2016 to 2019.2

We reviewed 165 patients discussed at our IgG4 MDM who had been classified as definite IgG4-RD, possible IgG4-RD or not IgG4-RD according to standard diagnostic criteria (HISORt for pancreas/biliary disease,3 Japanese Consensus Diagnostic Criteria for systemic disease,4 Consensus Statement on Pathology5) and MDM consensus opinion with prospective follow-up in a dedicated clinic. We applied the new ACR/EULAR classification criteria retrospectively to these cases to assess diagnostic …
Abstract 431: Probing the Pathogenic Mechanisms Underlying Ca <sub>V</sub> 1.2 Channelopathies
Authors: Moradeke Bamgboye, Maria Traficante, Kevin Herold, Josiah Owoyemi, Ivy Dick
Journal: Circulation Research (2020)

The Ca V 1.2 channel is essential to cardiac function. It is the sentinel that translates the electrical signal on the surface of the cell to the intracellular calcium cascade that leads to contraction. To allow the precise tuning of that is essential for cardiac function, Ca V 1.2 is subject to two forms of feedback regulation, voltage dependent inactivation (VDI) and calcium dependent inactivation (CDI). The first mutations described in Ca V 1.2 were causative of Timothy Syndrome (TS), a multisystem disorder with neurological, developmental and life-threatening cardiac symptoms, defined as long-QT type 8 (LQT8). These single point mutations occur in the S6, a region commonly associated with channel activation. In fact, the original TS mutations were shown to perturb channel activation as well as inactivation. Since this first description of TS, multiple additional mutations have been discovered in Ca V 1.2 and are associated with either TS-like or cardiac specific phenotypes. This phenotypic variance suggests that these mutations disrupt channel mechanisms in divergent ways. Moreover, for patients harboring mutations in Ca V 1.2, the cardiac symptoms have proven recalcitrant to conventional therapy including calcium channel blockers (CCBs). This therapeutic inadequacy reinforces the need for a better understanding of how mutations in the S6 disrupt channel function and how this affects therapeutic options for patients that carry them. Here we show that LQT8 mutations that cluster in the S6 of Ca V 1.2 do indeed have a variety of mechanistic underpinnings. This may account for the gradient of symptoms seen in patients with these mutations. In addition, we demonstrate that many of these mutant channels are resistant to block by CCBs, and this resistance strongly correlates to specific mechanistic perturbations of the channel. Thus, reliance on a CCB based therapeutic strategy is likely to leave many in a growing population of patients without a viable treatment option.
Long-Term Efficacy and Safety of Betibeglogene Autotemcel Gene Therapy for the Treatment of Transfusion-Dependent β-Thalassemia: Results in Patients with up to 6 Years of Follow-up
Authors: Janet L. Kwiatkowski, Mark C. Walters, Suradej Hongeng, Franco Locatelli, John E.J. Rasko, Marina Cavazzana, Ying Chen, Richard A. Colvin, Alexis A. Thompson
Journal: Blood (2020)
Novel therapies are changing treatment paradigms in metastatic prostate cancer
Authors: Eric Powers, Georgia Sofia Karachaliou, Chester Kao, Michael R. Harrison, Christopher J. Hoimes, Daniel J. George, Andrew J. Armstrong, Tian Zhang
Journal: Journal of Hematology & Oncology (2020)

Abstract Metastatic castration-resistant prostate cancer (mCRPC) remains a terminal diagnosis with an aggressive disease course despite currently approved therapeutics. The recent successful development of poly ADP-ribose polymerase (PARP) inhibitors for patients with mCRPC and mutations in DNA damage repair genes has added to the treatment armamentarium and improved personalized treatments for prostate cancer. Other promising therapeutic agents currently in clinical development include the radiotherapeutic 177-lutetium-prostate-specific membrane antigen (PSMA)-617 targeting PSMA-expressing prostate cancer and combinations of immunotherapy with currently effective treatment options for prostate cancer. Herein, we have highlighted the progress in systemic treatments for mCRPC and the promising agents currently in ongoing clinical trials.
Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–October 3, 2020
Authors: Laura D. Zambrano, Sascha Ellington, Penelope Strid, Romeo R. Galang, Titilope Oduyebo, Van T. Tong, Kate R. Woodworth, John F. Nahabedian, Eduardo Azziz-Baumgartner, Suzanne M. Gilboa, Dana Meaney-Delman, Amanda Akosa, Carolyne Bennett, Veronica Burkel, Daniel Chang, Augustina Delaney, Charise Fox, Isabel Griffin, Jason Hsia, Katie Krause, Elizabeth Lewis, Susan Manning, Yousra Mohamoud, Suzanne Newton, Varsha Neelam, Emily O’Malley Olsen, Mirna Perez, Megan Reynolds, Aspen Riser, Maria Rivera, Nicole M. Roth, Christina Sancken, Neha Shinde, Ashley Smoots, Margaret Snead, Bailey Wallace, Florence Whitehill, Erin Whitehouse, Lauren Zapata
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Studies suggest that pregnant women might be at increased risk for severe illness associated with coronavirus disease 2019 (COVID-19) (1,2). This report provides updated information about symptomatic women of reproductive age (15-44 years) with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19. During January 22-October 3, CDC received reports through national COVID-19 case surveillance or through the National Notifiable Diseases Surveillance System (NNDSS) of 1,300,938 women aged 15-44 years with laboratory results indicative of acute infection with SARS-CoV-2. Data on pregnancy status were available for 461,825 (35.5%) women with laboratory-confirmed infection, 409,462 (88.7%) of whom were symptomatic. Among symptomatic women, 23,434 (5.7%) were reported to be pregnant. After adjusting for age, race/ethnicity, and underlying medical conditions, pregnant women were significantly more likely than were nonpregnant women to be admitted to an intensive care unit (ICU) (10.5 versus 3.9 per 1,000 cases; adjusted risk ratio [aRR] = 3.0; 95% confidence interval [CI] = 2.6-3.4), receive invasive ventilation (2.9 versus 1.1 per 1,000 cases; aRR = 2.9; 95% CI = 2.2-3.8), receive extracorporeal membrane oxygenation (ECMO) (0.7 versus 0.3 per 1,000 cases; aRR = 2.4; 95% CI = 1.5-4.0), and die (1.5 versus 1.2 per 1,000 cases; aRR = 1.7; 95% CI = 1.2-2.4). Stratifying these analyses by age and race/ethnicity highlighted disparities in risk by subgroup. Although the absolute risks for severe outcomes for women were low, pregnant women were at increased risk for severe COVID-19-associated illness. To reduce the risk for severe illness and death from COVID-19, pregnant women should be counseled about the importance of seeking prompt medical care if they have symptoms and measures to prevent SARS-CoV-2 infection should be strongly emphasized for pregnant women and their families during all medical encounters, including prenatal care visits. Understanding COVID-19-associated risks among pregnant women is important for prevention counseling and clinical care and treatment.