tbuckley/cabot-search huggingface dataset:
HLA-A*03 and response to immune checkpoint blockade in cancer: an epidemiological biomarker study
Authors: Vivek Naranbhai, Mathias Viard, Michael Dean, Stefan Groha, David A Braun, Chris Labaki, Sachet A Shukla, Yuko Yuki, Parantu Shah, Kevin Chin, Megan Wind-Rotolo, Xinmeng Jasmine Mu, Paul B Robbins, Alexander Gusev, Toni K Choueiri, James L Gulley, Mary Carrington
Journal: The Lancet Oncology (2021)
Health Literacy in Surgical Oncology Patients: An Observational Study at a Comprehensive Cancer Center
Authors: Luke D. Rothermel, Claire C. Conley, Anuja L. Sarode, Michael F. Young, Zulema L. Uscanga, McKenzie McIntyre, Jason B. Fleming, Susan T. Vadaparampil
Journal: Journal of the National Comprehensive Cancer Network (2021)

Background: Low health literacy is associated with increased resource use and poorer outcomes in medical and surgical patients with various diseases. This observational study was designed to determine (1) the prevalence of low health literacy among surgical patients with cancer at an NCI-designated Comprehensive Cancer Center (CCC), and (2) associations between health literacy and clinical outcomes. Methods: Patients receiving surgery (N=218) for gastrointestinal (60%) or genitourinary cancers (22%) or sarcomas (18%) were recruited during their postsurgical hospitalization. Patients self-reported health literacy using the Brief Health Literacy Screening Tool (BRIEF). Clinical data (length of stay [LoS], postacute care needs, and unplanned presentation for care within 30 days) were abstracted from the electronic medical records 90 days after surgery. Multivariate linear and logistic regressions were used to examine the relationship between health literacy and clinical outcomes, adjusting for potential confounding variables. Results: Of 218 participants, 31 (14%) showed low health literacy (BRIEF score ≤12). In regression analyses including 212 patients with complete data, low health literacy significantly predicted LoS ( β = −1.82; 95% CI, −3.00 to −0.66; P =.002) and postacute care needs (odds ratio [OR], 0.25; 95% CI, 0.07–0.91). However, health literacy was not significantly associated with unplanned presentation for care in the 30 days after surgery (OR, 0.51; 95% CI, 0.20–1.29). Conclusions: This study demonstrates the prevalence of low health literacy in a surgical cancer population at a high-volume NCI-designated CCC and its association with important clinical outcomes, including hospital LoS and postacute care needs. Universal screening and patient navigation may be 2 approaches to mitigate the impact of low health literacy on postsurgical outcomes.
Research in brief
Authors: Sharmila Devi
Journal: The Lancet Infectious Diseases (2021)

Researchers have found that SARS-CoV-2 is prevented from docking and invading the body's cells only when people are able to form specific antibodies against the folded receptor-binding domain (RBD) of the spike protein, and this docking site does not change with significant virus mutations. The researchers used microarray or chip technology, in which a large number of viral antigens were applied to a microscopic chip by a robotic spotting machine. Antibodies were exclusively formed against the intact, three-dimensionally folded spike protein and not against parts of it.
Lymphocyte Recovery Following Autologous Hematopoietic Stem Cell Transplant in Classical Hodgkin Lymphoma
Authors: Ashley Rose, Quinto J Gesiotto, Leidy Isenalumhe, Farhad Khimani, Hien D. Liu, Sameh Gaballa, Julio C. Chavez, Bijal D. Shah, Javier Pinilla Ibarz, Celeste Bello, Lubomir Sokol, Hayder Saeed
Journal: Blood (2021)
11P Senescent immune phenotype (SIP) status that predicts resistance to immune checkpoint blockers (ICB) among CMV+ advanced non-small cell lung cancer (aNSCLC) patients is not associated with chronic type I IFN signature
Authors: M. Naigeon, C. de Oliveira, F-X. Danlos, B. Duchemann, P. Saulnier, L. Boselli, J-M. Jouniaux, F. Griscelli, A. Marabelle, L. Lacroix, L. Cassard, B. Besse, N. Chaput
Journal: Annals of Oncology (2021)
JAMA Neurology
Authors: Hooman Kamel, New York, Bernard Chang, Dena Dubal, San Francisco, Ari Green, Michael Okun, Florida Gil, D Rabinovici, Kate Denevan, Nancy Hills, Cynthia Armand, Samuel Pleasure, Elan Guterman, Megan Richie, Maulik Shah, Sidra Bonner, Ann Arbor, Heather Hsu, Andrew Ibrahim, Carl Bazil, Alberto Espay, Eva Cincinnati, Ann Feldman, Nathalie Arbor, New Jetté, Ruchira York, Pooja Pittsburgh, Susan Ohio, Berkeley Landau, California Babak, B Navi, Daniel Ontaneda, Stanley Prusiner, Sonja Scholz, Maryland Paul, C Van Ness, Allison Willis, Harold Wolff, H Merritt, Fred Plum, Maurice Van Allen, Robert Joynt, Roger Rosenberg, Phil Fontanarosa, Annette Flanagin, Brenda Gregoline, Tracy Frey, Iris Lo, Kevin Brown, Erin Keenan, Rebecca Langley, M Newman, Connie Manno Senior, Sara Billings, Denise Steinhauser, Joe Wixted, Ahmed Avendano, Kim Boler, Rhonda Brown, Fin Carter, Michael Deegan, Daniel Degroot, Euwanaha Joiner-Smith, Joshua Lane, Cindy Rendlen, Ellen Yoshihara, Annissa Zak, Circulation Services, Julie Burton, Ronna Hewitt, Mary Sieck, Geneine Someren, Jamaal Vargas, Content Systems, Mike Bujewski, Nathan Mitre, Digital Production, Regina Brownlee, Amanda Camino, Brenda Chandler-Grayer, Emily Dunn, Amy Evers, Maleeka Holden, Teri Hutchison, Dan Knowles, Joshua Lampinen, Natalie Marsh, Patricia Panek, Marla Seidell, La Son, Diggs Sledge, Julian Graphics, Joe Amft, Jonathan Chala, James Collver, Maria Duda, Fred Furtner, Carolyn Hall, Maria Kowalkowski, Proofreading Carol, Joy Farrell, Maria Giannini, Sasha Grossman, Kate Lander, Judith Literskis, Teresa Omiotek, Michael Ryder, James Madara, S Josephson
Journal: JAMA Neurology (2021)

The mission of JAMA Neurology is to publish and disseminate scientific information primarily important for physicians caring for people with neurologic disorders and for those interested in the structure and function of the normal and diseased human nervous system.The specifi c aims are to (1) publish timely original research, including clinical trials that will directly improve clinical neurologic care and that will inform efforts to improve neurological health and promote health care equity; (2) report translational research that is pertinent to the understanding of neurologic disease; (3) address topics of practice, ethics, education, and public health that are a key part of modern medicine; and (4) provide a forum for discussion and publication of important topics including bias, racism, and diversity.This information will be published only after extensive review by scientifi c peers and journal editors so that clarity, rigor, originality, and precision are ensured.
145P Neoadjuvant chemotherapy combined with camrelizumab for locally advanced head and neck squamous cell carcinoma: A phase II trial
Authors: K. Yang, X. Zhang, Z. Zhang, B. Wu, G. Peng, J. Huang, Q. Ding, G. Xiao, H. Ma, C. Yang, X. Xiong, L. Shi, J. Yang, X. Hong, J. Wei, Y. Qin, Y. Zhong, Y. Zhou, X. Zhao, Y. Leng
Journal: Annals of Oncology (2021)
Low Incidence of COVID-19 Infection in Patients with Acute Myeloid Leukemia Undergoing Reduced Intensity/Venetoclax Based Treatment: Initial Results of the PACE Prospective Clinical Study from the UK Trials Acceleration Program
Authors: (Justin) Ching Ting Loke, Charlotte Gaskell, Sonia Fox, Rachel Fletcher, Catherine Thomas, Louise Hopkins, Anita Kumari, Rebecca H. Boucher, Jane Nunnick, Steve Knapper, Arpad Toth, Jennifer Byrne, Jenny O'Nions, Anjum Khan, Rui Zhao, Arvind Pillai, Eleni Tholouli, Moez Dungarwalla, Katie Randall, Richard Dillon, Duncan Murray, Dominic Culligan, Mary Frances McMullin, Yuen Ling Tracey Chan, Victoria Drew, Vidhya Murthy, Pramila Krishnamurthy, Pratap Neelakantan, Tom Rider, Farooq A Wandroo, Mark Rafferty, Ya-Wen Huang, Sally Moore, Priyanka Mehta, David G Partridge, Charles Craddock, David Lowe, Simon J. Stanworth
Journal: Blood (2021)
Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection
Authors: Alexander C. Dowell, Megan S. Butler, Elizabeth Jinks, Gokhan Tut, Tara Lancaster, Panagiota Sylla, Jusnara Begum, Rachel Bruton, Hayden Pearce, Kriti Verma, Nicola Logan, Grace Tyson, Eliska Spalkova, Sandra Margielewska-Davies, Graham S. Taylor, Eleni Syrimi, Frances Baawuah, Joanne Beckmann, Ifeanyichukwu O. Okike, Shazaad Ahmad, Joanna Garstang, Andrew J. Brent, Bernadette Brent, Georgina Ireland, Felicity Aiano, Zahin Amin-Chowdhury, Samuel Jones, Ray Borrow, Ezra Linley, John Wright, Rafaq Azad, Dagmar Waiblinger, Chris Davis, Emma C. Thomson, Massimo Palmarini, Brian J. Willett, Wendy S. Barclay, John Poh, Gayatri Amirthalingam, Kevin E. Brown, Mary E. Ramsay, Jianmin Zuo, Paul Moss, Shamez Ladhani
Journal: Nature Immunology (2021)

Abstract SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3–11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.
Oxytocin normalizes altered circuit connectivity for social rescue of the Cntnap2 knockout mouse
Authors: Katrina Y Choe, Richard A I Bethlehem, Martin Safrin, Hongmei Dong, Elena Salman, Ying Li, Valery Grinevich, Peyman Golshani, Laura A DeNardo, Olga Peñagarikano, Neil G Harris, Daniel H Geschwind
Journal: Neuron (2021)
Basal lamina changes in neurodegenerative disorders
Authors: Benjamin Nguyen, Gregory Bix, Yao Yao
Journal: Molecular Neurodegeneration (2021)

Abstract Background Neurodegenerative disorders are a group of age-associated diseases characterized by progressive degeneration of the structure and function of the CNS. Two key pathological features of these disorders are blood-brain barrier (BBB) breakdown and protein aggregation. Main body The BBB is composed of various cell types and a non-cellular component---the basal lamina (BL). Although how different cells affect the BBB is well studied, the roles of the BL in BBB maintenance and function remain largely unknown. In addition, located in the perivascular space, the BL is also speculated to regulate protein clearance via the meningeal lymphatic/glymphatic system. Recent studies from our laboratory and others have shown that the BL actively regulates BBB integrity and meningeal lymphatic/glymphatic function in both physiological and pathological conditions, suggesting that it may play an important role in the pathogenesis and/or progression of neurodegenerative disorders. In this review, we focus on changes of the BL and its major components during aging and in neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). First, we introduce the vascular and lymphatic systems in the CNS. Next, we discuss the BL and its major components under homeostatic conditions, and summarize their changes during aging and in AD, PD, and ALS in both rodents and humans. The functional significance of these alterations and potential therapeutic targets are also reviewed. Finally, key challenges in the field and future directions are discussed. Conclusions Understanding BL changes and the functional significance of these changes in neurodegenerative disorders will fill the gap of knowledge in the field. Our goal is to provide a clear and concise review of the complex relationship between the BL and neurodegenerative disorders to stimulate new hypotheses and further research in this field.
Circulating cell-free double-stranded DNA and metabolic derangements in idiopathic pulmonary fibrosis: a new association
Authors: Yuben P Moodley
Journal: Thorax (2021)

Aim: We sought to clarify whether the expression of toll-like receptors (TLR) in Merkel cell carcinoma (MCC) is linked to tumor and patient characteristics, especially the presence of Merkel cell polyoma virus (MCV). Materials and Methods: The study comprised of 128 patients with data on Merkel cell polyomavirus (MCV) status and clinical features were included in the study. Immunohistochemistry for TLR expression was performed on tissue microarray (TMA) slides. Results: TLR 2, 4, 5, 7 and 9 expression was noted in most of the tumor specimens. Decreased expression of TLR 9 correlated strongly with MCV positivity. Cytoplasmic TLR 2 expression correlated with small tumor size, while nuclear TLR 2 and TLR 5 expressions with larger tumors. Increased nuclear TLR 4 expression and decreased TLR 7 expression were associated with older age. Conclusion: TLR 2, 4, 5, 7 and 9 appear to reflect certain clinicopathological variables and prognostic markers of MCC tumors.
Abstract 10739: Simulation Based Assessment of Trainee’s Performance in Post-Cardiac Arrest Resuscitation
Authors: Afrah A Ali, Wan-Tsu Chang, Ali Tabatabai, Melissa B Pergakis, Camilo A Gutierrez, Benjamin Neustein, Gregory E Gilbert, Jamie E Podell, Gunjan Parikh, Neeraj Badjatia, Melissa Motta, David P Lerner, Nicholas A Morris
Journal: Circulation (2021)

Up to 22% of patients survive to hospital admission following out-of-hospital cardiac arrest (OHCA). Post cardiac arrest is complex and requires a multidisciplinary approach. Our aim is to assess trainee’s performance in managing post-cardiac arrest care using a high-fidelity manikin-based simulation. We also sought to obtain evidence regarding the validity of our findings. Methods: In this prospective, observational, simulation based study, participants ranging from sub interns to attending physicians evaluated and managed a post cardiac arrest patient, complicated by refractory status epilepticus. Critical actions were developed by a modified Delphi approach based on relevant American Heart Association guidelines and the Neurocritical Care Society’s Emergency Neurological Life Support protocols. The primary outcome measure was the critical action item sum score. We sought validity evidence to support our findings by comparing trainees’ performance across four levels of training. Results: Forty-nine participants completed the simulation. The mean sum of critical actions completed by participants was 10/21(49%). Eleven(22%) participants verbalized a differential diagnosis for the arrest. Thirty-two(65%) recognized the abnormal electrocardiography, and consulted cardiology. Forty trainees(81%) independently decided to start target temperature management (TTM), but only 20(41%) insisted on TTM when asked to reconsider. There was an effect of level of training on critical action checklist sum scores (novice mean score [standard deviation (SD)] = 4.8 (1.8) vs. intermediate mean score (SD) = 10.4 (2.1) vs. advanced mean score (SD) = 11.6 (3.0) vs. expert mean score (SD) = 14.7 (2.2) Conclusions: High-fidelity manikin-based simulation holds promise as an assessment tool in the performance of post-cardiac arrest care. Areas for further educational initiatives to improve performance include diagnostic work-up of OHCA and implementation of TTM.
How to Treat Prostate Cancer With Androgen Deprivation and Minimize Cardiovascular Risk
Authors: Vivek Narayan, Ashley E. Ross, Ravi B. Parikh, Anju Nohria, Alicia K. Morgans
Journal: JACC CardioOncology (2021)

• Androgen deprivation therapy is associated with metabolic derangements due to profound hypogonadism that can increase the risk of CV disease in prostate cancer survivors. • Therapeutic advances have resulted in prolonged patient exposure to androgen deprivation therapy, thereby increasing CV complications for many prostate cancer survivors. • A systematic approach to monitoring and addressing reversible CV risk factors and purposeful engagement in multidisciplinary care between oncologists, urologists, and cardiologists is critical to optimizing CV outcomes in men with prostate cancer.
WDR26 and MTF2 are therapeutic targets in multiple myeloma
Authors: Fumou Sun, Yan Cheng, Jesse D. Riordan, Adam Dupuy, Wendy Dubois, Michael Pisano, Jing Dong, Beverly Mock, Fenghuang Zhan, Parameswaran Hari, Siegfried Janz
Journal: Journal of Hematology & Oncology (2021)

Abstract Unbiased genetic forward screening using retroviral insertional mutagenesis in a genetically engineered mouse model of human multiple myeloma may further our understanding of the genetic pathways that govern neoplastic plasma cell development. To evaluate this hypothesis, we performed a tumor induction study in MYC-transgenic mice infected as neonates with the Moloney-derived murine leukemia virus, MOL4070LTR. Next-generation DNA sequencing of proviral genomic integration sites yielded rank-ordered candidate tumor progression genes that accelerated plasma cell neoplasia in mice. Rigorous clinical and biological validation of these genes led to the discovery of two novel myeloma genes: WDR26 (WD repeat-containing protein 26) and MTF2 (metal response element binding transcription factor 2). WDR26, a core component of the carboxy-terminal to LisH (CTLH) complex, is overexpressed or mutated in solid cancers. MTF2, an ancillary subunit of the polycomb repressive complex 2 (PRC2), is a close functional relative of PHD finger protein 19 (PHF19) which is currently emerging as an important driver of myeloma. These findings underline the utility of genetic forward screens in mice for uncovering novel blood cancer genes and suggest that WDR26-CTLH and MTF2-PRC2 are promising molecular targets for new approaches to myeloma treatment and prevention.
A Phase 1/2 Study of Lazertinib 240 mg in Patients With Advanced EGFR T790M-Positive NSCLC After Previous EGFR Tyrosine Kinase Inhibitors
Authors: Byoung Chul Cho, Ji-Youn Han, Sang-We Kim, Ki Hyeong Lee, Eun Kyung Cho, Yun-Gyoo Lee, Dong-Wan Kim, Joo-Hang Kim, Gyeong-Won Lee, Jong-Seok Lee, Byoung Yong Shim, Jin-Soo Kim, Sang Hoon Chun, Sung Sook Lee, Hye Ryun Kim, Min Hee Hong, Jin Seok Ahn, Jong-Mu Sun, Youngjoo Lee, Dae Ho Lee, Ji Ah Kang, NaMi Lee, Mi-Jung Kwon, Carin Espenschied, Arielle Yablonovitch, Myung-Ju Ahn
Journal: Journal of Thoracic Oncology (2021)

IntroductionThis integrated analysis of a phase 1/2 study (NCT03046992) evaluated the efficacy and safety of lazertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), in patients with advanced EGFR T790M-positive NSCLC after previous EGFR TKI therapy.MethodsAdults with EGFR mutation-positive NSCLC that progressed after prior EGFR-directed TKIs received once daily oral lazertinib 240 mg continuously until disease progression. Prior TKIs to treat T790M-positive NSCLC were prohibited. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included progression-free survival, overall survival, and intracranial ORR.ResultsA total of 78 patients received lazertinib 240 mg at 17 centers in South Korea. Among patients with T790M-positive tumors at baseline (N = 76), one (1.3%) had a complete response and 41 (53.9%) had partial responses, giving an ORR of 55.3% (95% confidence interval [CI]: 44.1–66.4). Median progression-free survival was 11.1 months (95% CI: 5.5–16.4). Median overall survival was not reached (median follow-up = 22.0 mo). In patients with measurable intracranial lesions (n = 7), one (14.3%) had a complete intracranial response and five (71.4%) had partial responses, giving an intracranial ORR of 85.7% (95% CI: 59.8%–100.0%). The most common treatment-emergent adverse events were rash (37.2%), pruritus (34.6%), and paresthesia (33.3%); most were mild to moderate in severity. Serious drug-related adverse events occurred in three patients (gastritis, pneumonia, pneumonitis). The major mechanism of resistance was EGFR T790M loss.ConclusionsLazertinib 240 mg/d has a manageable safety profile with durable antitumor efficacy, including brain metastases, in patients with advanced T790M-positive NSCLC after previous EGFR TKI therapy.
Effectiveness of an Analytics-Based Intervention for Reducing Sleep Interruption in Hospitalized Patients
Authors: Nader Najafi, Andrew Robinson, Mark J. Pletcher, Sajan Patel
Journal: JAMA Internal Medicine (2021)

Sleep has major consequences for physical and emotional well-being. Hospitalized patients experience frequent iatrogenic sleep interruptions and there is evidence that such interruptions can be safely reduced.To determine whether a clinical decision support tool, powered by real-time patient data and a trained prediction algorithm, can help physicians identify clinically stable patients and safely discontinue their overnight vital sign checks.A randomized clinical trial, with inpatient encounters randomized 1:1 to intervention vs usual care, was conducted from March 11 to November 24, 2019. Participants included physicians serving on the primary team of 1699 patients on the general medical service (not in the intensive care unit) of a tertiary care academic medical center.A clinical decision support notification informed the physician if the patient had a high likelihood of nighttime vital signs within the reference ranges based on a logistic regression model that used real-time patient data as input. The notification provided the physician an opportunity to discontinue measure of nighttime vital signs, dismiss the notification for 1 hour, or dismiss the notification for that day.The primary outcome was delirium, as determined by bedside nurse assessment of Nursing Delirium Screening Scale scores, a standardized delirium screening tool (delirium diagnosed with score ≥2). Secondary outcomes included mean nighttime vital sign checks. Potential harms included intensive care unit transfers and code blue alarms. All analyses were conducted on the basis of intention-to-treat.A total of 1930 inpatient encounters in 1699 patients (intervention encounters: 566 of 966 [59%] men; mean [SD] age, 53 [15] years) were randomized. In the intervention vs control arm, there was a significant decrease in the mean (SD) number of nighttime vital sign checks (0.97 [0.95] vs 1.41 [0.86]; P < .001) with no increase in intensive care unit transfers (49 [5%] vs 47 [5%]; P = .92) or code blue alarms (2 [0.2%] vs 9 [0.9%]; P = .07). The incidence of delirium was not significantly reduced (108 [11%] vs 123 [13%]; P = .32).While this randomized clinical trial found no difference between groups in the primary outcome, delirium incidence, the secondary findings indicate that a real-time prediction algorithm embedded within a clinical decision support tool in the electronic health record can help physicians identify clinically stable patients who can forgo routine vital sign checks, safely giving them greater opportunity to sleep. Other aspects of hospital care that depend on clinical stability, such as level of care or cardiac monitoring, may be amenable to a similar intervention.ClinicalTrials.gov Identifier: NCT04046458.