tbuckley/cabot-search huggingface dataset:
SARS-CoV-2 multiepitope vaccineconstructs designed to drive long-term immunity in themajority of the population
Authors: Mark Yarmarkovich, John M. Warrington, Alvin Farrel, John M. Maris
Journal: Clinical Cancer Research (2020)

The current SARS-CoV-2 pandemic has precipitated an urgent need for a safe and effective vaccine to bedeveloped and deployed in a highly accelerated timeframe as compared to standard vaccine developmentprocesses  Upfront selection of epitopes most likely to induce a safe and effective immune response can acceleratethese efforts  Optimally designed vaccines maximize immunogenicity towards regions of proteins that contributemost to protective immunity, while minimizing the antigenic load contributed by unnecessary protein domains thatmay result in autoimmunity, reactogenicity, or enhanced infectivity  Adopting tools developed for population-scalecharacterization of HLA presentation of tumor antigens and cross-reactivity of TCRs with tumor self-antigens, wehave generated an immunogenicity map of SARS-CoV-2 to inform vaccine design based on analyses across fiveparameters: 1) stimulation of CD4 and CD8 T cells;2) immunogenicity across the majority of human HLA alleles;3)targeting both evolutionarily conserved regions, as well as newly divergent regions of the virus that increaseinfectivity;4) targeting linear and conformational B-cell epitopes;and 5) targeting viral regions with the highestdegree of dissimilarity to the self-immunopeptidome such as to maximize safety and immunogenicity  Using theseanalyses, we have generated 11 SARS-CoV-2 vaccine constructs optimized for long-term immunity across themajority of the population  These constructs contain combinations of epitopes selected from our analysis such as todrive affinity-enhanced memory response in combination with current spike protein vaccine strategies, for use as T-cell vaccines, and a stand-alone vaccine designed to drive memory B- and T-cell responses in the majority of thepopulation  Epitopes were optimized using our immunogenicity algorithm to minimize immunogenicity across thejunctions between epitopes and cloned into pVAX vectors, using signal peptides targeting the lysosome, ER, andcytoplasmic secretion, such as to promote presentation to CD4, CD8, and B cells, respectively  Finally, we describemethods for identifying immunodominant epitopes arising from vaccination using barcoded, multiplexed tetramers Vaccine constructs are currently undergoing testing in transgenic mice expressing human HLA-A2  We expect thatthese constructs will help drive long-term immunity across the population, targeting conserved regions acrossmultiple coronaviruses
Impact of CDK 4/6i withdrawal or dose adjustment on COVID-19 incidence in HR+/HER2-mBC patients during the pandemic
Authors: P. Tolosa, A. Sanchez-Torre, H. B. De Cabo, R. Sanchez-Bayona, M. Herrera, R. Yarza, L. Lema, L. Manso, E. Ciruelos
Journal: Clinical Cancer Research (2020)

Background: On January 30th, 2020, the World Health Organization (WHO) declared public health emergencies ofinternational concern (PHEIC) because of the outbreak of SARS-CoV2 and coronavirus disease 2019 (COVID-19) It has rapidly expanded all around the world, highlighting Madrid as one of the cities with a highest incidence Oncologists have had to adapt treatments in order to reduce the pandemic impact  CDK4/6 inhibitors (CDK4/6i) incombination with hormone therapy are the standard of care in hormone receptor-positive (HR+), HER2-negative(HER2-) metastatic breast cancer (mBC) patients (P)  Asymptomatic neutrophil count decrease is the most frequenttoxicity of these agents and may negatively impact on incidence and severity of COVID-19 disease  Methods: Hospitalized P increased exponentially from 10 to 16 March 2020 in our hospital  78 P diagnosed withER+/HER2- mBC were on CDK4/6i treatment at that time  At the physicians' discretion CDK4/6i withdrawal or doseadjustment was performed (considering age, comorbidities, and presence of previous neutropenia)  The presence ofrisk factors such as advanced age or previous neutropenia were key issues when deciding to withdraw or adjustCDK4/6i  We conducted a retrospective analysis to evaluate this decision  All P were selected, and data werecollected on May 15th, 2020  The main end point was to evaluate the impact of CDK4/6i withdrawal or doseadjustment (non-exposed) on the incidence of COVID-19 defined as high clinical suspicion (including anosmia) orpositive PCR;we estimate the odds ratio (OR) through logistic regression  As secondary objectives P characteristics were evaluated to identify and control potential confounding factors, we also calculate adjusted OR by multivariateanalysis  Results: A total of 78 P were evaluated, 44 P treated with palbociclib, 21 with ribociclib, and 13 with abemaciclib incombination with hormonal therapies  Incidence of COVID-19 was 7 7% (6/78 P), 12 8% (5/39) in exposed P, and2 7% (1/39) in non-exposed P  The OR for exposed patients was 5 8 IC 95% (0 62 to 50 25) p 0,077  Age over 65years and bone-only disease were associated with a lower COVID 19 relative risk, while diabetes mellitus wasassociated with a higher incidence  None of the 25 patients over age 70 were infected  In multivariate analysis theadjusted OR for exposed P was 7 68 (p 0 24)  Incidence of COVID-19 was numerically higher in patients treated with ribociclib (14 29%) compared to palbociclib (4 55%) or abemaciclib (7 69%)  No risk of progression disease wasobserved in P who had CDK 4/6i withdrawn or dose reduction (p 0 98)  Conclusions: Despite the lack of statistical significance, CDK4/6i withdrawn or dose reduction may reduce theincidence of COVID-19  Greater collection of data during COVID-19 pandemic is needed and will provide us withstrong evidence to make decisions in case of new outbreaks
Erratum : Curriculum for small-bowel capsule endoscopy and device-assisted enteroscopy training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement (Endoscopy (2020) 52 DOI: 10.1055/a-1185-1289)
Authors: Reena Sidhu, Stefania Chetcuti Zammit, Peter Baltes, Cristina Carretero, Edward J. Despott, Alberto Murino, Xavier Dray, David S. Sanders, Martin Keuchel, Evelien Dekker, James E. East, Gavin Johnson, Pedro Pimentel-Nunes, Marianna Arvanitakis, Thierry Ponchon, Mario Dinis-Ribeiro, Raf Bisschops
Journal: Endoscopy (2020)

In the above-mentioned article, the name of Stefania Chetcuti Zammit has been corrected. This was corrected in the online version on June 26, 2020.
Analysis of systemic therapy delivery for gastrointestinal cancer patients during the COVID-19 pandemic.
Authors: Robert Power, Claire O'Donohoe, Cathy Enright, Louise Glennon, Lisa McDowell, David James Gallagher, Maeve Aine Lowery
Journal: Journal of Clinical Oncology (2020)

301 Background: As of June 16, 0.51% of the Irish population has had a confirmed diagnosis of COVID-19, and incidence of new infections peaked on April 10. Cancer patients treated with systemic anticancer therapy (SACT) may have increased risk of contracting COVID-19, and greater incidence of adverse outcomes. We aimed to assess the impact of a COVID-19 SACT clinical pathway on the incidence of SARS-CoV-2 infection in gastrointestinal cancer patients, and alterations to SACT regimens attributed to the COVID-19 pandemic. Methods: A COVID-19 SACT clinical pathway for patients undergoing treatment in a haematology oncology day care (HODC) service was designed and implemented. Interventions included visitor restrictions, telephone clinics, mandatory masks and temperature checks for staff, social distancing at all workspaces, and establishment of a COVID-19 screening pod. A prospective registry of all gastrointestinal cancer patients attending the HODC clinic between February 1 and April 31 2020 was initiated following institutional ethics board approval. Clinical data were retrieved from electronic health records including demographics, performance status, comorbidities, SACT regimen (including changes to treatment), SARS-CoV-2 testing, and radiologic treatment responses. Results: In this period, 175 gastrointestinal (88 gastroesophageal, 8 hepatobiliary, 79 colorectal) cancer patients attended 931 HODC outpatient clinics. Of this, 41 (23%) underwent at least one SARS-CoV-2 test. No patients tested positive. Two gastroesophageal cancer patients undergoing neoadjuvant chemoradiotherapy presented with SARS-CoV-2-negative suspected viral pneumonia and respiratory failure; both required intensive care unit admission and one died. SACT regimen was altered in 48 (27%) patients due to the COVID-19 pandemic. Changes involved prescription of alternative oral therapies (21; 12%), treatment breaks (17; 9%), and stopping treatment (11; 6%). Most (88%) regimen changes took place in a single 3-week period (6-27 March) that coincided with the announcement of government-mandated social distancing measures. Conclusions: Implementing a COVID-19 SACT clinical pathway resulted in a low incidence of SARS-CoV-2 infection in gastrointestinal patients undergoing systemic treatment. SACT regimen changes were common; prospective monitoring of this cohort is ongoing to determine whether these alterations affect patient outcomes.
Association of Measurable Residual Disease With Survival Outcomes in Patients With Acute Myeloid Leukemia
Authors: Nicholas J. Short, Shouhao Zhou, Chenqi Fu, Donald A. Berry, Roland B. Walter, Sylvie D. Freeman, Christopher S. Hourigan, Xuelin Huang, Graciela Nogueras Gonzalez, Hyunsoo Hwang, Xinyue Qi, Hagop Kantarjian, Farhad Ravandi
Journal: JAMA Oncology (2020)

Measurable residual disease (MRD) refers to neoplastic cells that cannot be detected by standard cytomorphologic analysis. In patients with acute myeloid leukemia (AML), determining the association of MRD with survival may improve prognostication and inform selection of efficient clinical trial end points.
Adherence to and determinants of guideline-recommended biomarker testing and targeted therapy in patients with gastroesophageal adenocarcinoma: Insights from routine practice.
Authors: Kelsey S. Lau-Min, Yimei Li, Jennifer Rachel Eads, Ronac Mamtani, Kelly D. Getz
Journal: Journal of Clinical Oncology (2020)

12 Background: Precision oncology has transformed care for patients with advanced HER2+ gastroesophageal adenocarcinoma (GEA), where the addition of anti-HER2 therapy with trastuzumab improves overall survival and is now incorporated into national guidelines. However, little is known about adherence to and determinants of timely HER2 testing and trastuzumab initiation in routine care. Methods: We performed a retrospective study of advanced GEA diagnosed between 1/2011 and 6/2019 in the nationwide Flatiron Health EHR-derived deidentified database. We calculated annual prevalence and identified determinants of timely HER2 testing (defined within 21 days after advanced diagnosis) and timely first-line trastuzumab initiation (defined within 14 days after a HER2+ result). Log binomial regressions estimated adjusted prevalence ratios (PR) comparing timely HER2 testing and trastuzumab initiation by patient and tumor characteristics. Multiple imputation was conducted for missing data. Results: We included 6,479 patients with advanced GEA; 973 were HER2+ of whom 585 (60.1%) initiated trastuzumab. Prevalence of timely HER2 testing increased from 22.4% in 2011 to 44.5% in 2019; timely trastuzumab initiation remained stable at 18.0% over the same period. No appreciable differences in timely testing or trastuzumab initiation by age, sex, race or payer category were noted. Patients with early-stage GEA who subsequently developed metastatic disease were less likely to undergo timely HER2 testing and trastuzumab initiation than those with metastatic disease at diagnosis (PR 0.69, 95% CI 0.64-0.75 for testing; PR 0.44, 95% CI 0.28-0.69 for therapy). Similar findings were seen for patients who did not receive surgery (PR 0.56, 95% CI 0.47-0.65 for testing; PR 0.57, 95% CI 0.22-1.46 for therapy). Patients who started chemotherapy before learning their HER2 status (PR 1.42, 95% CI 1.05-1.90) and those with concordant HER2 immunohistochemistry and FISH results (PR 1.76, 95% CI 0.99-3.13) were more likely to initiate timely trastuzumab. Conclusions: Among patients with advanced GEA, guideline-recommended HER2 testing and anti-HER2 therapy initiation remain underutilized. Misclassification due to missing testing or treatment performed outside the Flatiron Network is a study limitation. Uptake of precision oncology may improve with implementation of universal HER2 testing of GEA patients regardless of stage and reflex multidisciplinary review of discordant HER2 test results.
Patient concerns during the COVID-19pandemic: Lessons from the lung cancer community
Authors: J. Freeman-Daily, U. Basu Roy, K. Norris, B. Bunn, J. Baranski, C. Chin, A. C. Moore
Journal: Clinical Cancer Research (2020)

Background: The COVID-19 pandemic generated intense concern across the lung cancer (LC) community due toreports that LC patients are at higher risk for severe illness and/or death from COVID-19  Patient advocacy groups(PAGs) may need to revise their programs in order to address these concerns  To understand the specific needs ofthe LC community, LC PAGs conducted a survey to ask USA LC patients and caregivers to rank their concernsacross a number of COVID-19-related topics  Methods: A rapid needs assessment survey was created with input from LC patients and PAGs to cover threedomains: General Information About COVID-19, What If I Get COVID-19, and COVID-19 Impact on Lung CancerCare  The first two domains had 8 items while the third had 9 items  LC patients and caregivers in the USA wereasked to rate their level of concern about each item on a 5-point Likert scale (where 1 = Not at all concerned to 5 =Extremely concerned)  Data were collected for 5 days through an online platform during the first week of June Weighted responses and percentages were calculated for each item using SPSS  Results: Eighty-three participants responded to the survey;most were dealing with non-small cell LC, and 70%were stage IV  1  General Information About COVID-19: Two top areas of concern were “How to know when it's safeto return to normal activity” (80 5% very or extremely concerned), and “How to protect myself from COVID-19” (71%very or extremely concerned)  On the other hand, participants were least concerned about “Origins of SARS-CoV-2-(only 25% very or extremely concerned) and “Stress/Anxiety affecting wellbeing” (only 25% very or extremelyconcerned)  2  What If I Get COVID-19: More than 80% of respondents were very or extremely concerned about-Vaccines/Treatments for COVID-19” and “Learning about risk factors that make LC patients vulnerable to COVID-19 ” Interestingly, “Preparation of legal documents in anticipation of COVID-19” was not a top concern forparticipants (only 23% were very or extremely concerned)  3  COVID-19 Impact on Lung Cancer Care: Participants were very or extremely concerned that “The pandemic would delay or terminate LC research” (77%) and “Berefused treatment due to limit resources” (66%)  4  Lastly, we evaluated patient concerns by age  Respondents werestratified into two groups: 60 and younger or 61 and older  Those 60 and younger were more concerned about their-cancer center being a COVID-19 hotspot” and the “delay or termination in LC research” whereas those 61 andolder were more concerned that they “would not be able to contact their health care provider ” Conclusions: By collaborating with patients to identify and rank specific concerns of the LC community, patientadvocacy groups can be better positioned to prioritize those programs and services that will help patients andcaregivers navigate the ongoing challenges of the COVID-19 pandemic
Surgical Coaching—It’s All About the Relationship
Authors: Ian M. Kratzke, Muneera R. Kapadia
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
A global effort to understand the riddles of COVID-19 and cancer
Authors: Vivek Subbiah
Journal: Nature Cancer (2020)

Cancer has found a formidable foil in COVID-19, and this has brought to the fore the early concerns that COVID-19 could have a deeper impact on oncology patients. Two studies now provide insights into the enigma surrounding the determinants of the worsening of COVID-19 symptoms in patients with cancer.
Mental Illness and Stigma in Surgical Residencies—An Unspoken Truth
Authors: Whitney W. Fu, Paul G. Gauger, Erika A. Newman
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
A genome assembly and the somatic genetic and epigenetic mutation rate in a wild long-lived perennial Populus trichocarpa
Authors: Brigitte T. Hofmeister, Johanna Denkena, Maria Colomé-Tatché, Yadollah Shahryary, Rashmi Hazarika, Jane Grimwood, Sujan Mamidi, Jerry Jenkins, Paul P. Grabowski, Avinash Sreedasyam, Shengqiang Shu, Kerrie Barry, Kathleen Lail, Catherine Adam, Anna Lipzen, Rotem Sorek, Dave Kudrna, Jayson Talag, Rod Wing, David W. Hall, Daniel Jacobsen, Gerald A. Tuskan, Jeremy Schmutz, Frank Johannes, Robert J. Schmitz
Journal: Genome biology (2020)

Abstract Background Plants can transmit somatic mutations and epimutations to offspring, which in turn can affect fitness. Knowledge of the rate at which these variations arise is necessary to understand how plant development contributes to local adaption in an ecoevolutionary context, particularly in long-lived perennials. Results Here, we generate a new high-quality reference genome from the oldest branch of a wild Populus trichocarpa tree with two dominant stems which have been evolving independently for 330 years. By sampling multiple, age-estimated branches of this tree, we use a multi-omics approach to quantify age-related somatic changes at the genetic, epigenetic, and transcriptional level. We show that the per-year somatic mutation and epimutation rates are lower than in annuals and that transcriptional variation is mainly independent of age divergence and cytosine methylation. Furthermore, a detailed analysis of the somatic epimutation spectrum indicates that transgenerationally heritable epimutations originate mainly from DNA methylation maintenance errors during mitotic rather than during meiotic cell divisions. Conclusion Taken together, our study provides unprecedented insights into the origin of nucleotide and functional variation in a long-lived perennial plant.
Erratum: Addendum: Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China (Nature medicine (2020) 26 4 (506-510))
Authors: J. T. Wu, K. Leung, M. Bushman, N. Kishore, R. Niehus, P. M. de Salazar, B. J. Cowling, M. Lipsitch, G. M. Leung
Journal: Nature Medicine (2020)
Pituitary Metastases Discovered by 18F-FDG PET/CT During Other Cancers Monitoring
Authors: Andra Piciu, Alexandru Mester, Doina Piciu
Journal: Clinical Nuclear Medicine (2020)

F-FDG PET/CT might discover incidental pituitary lesions. We present the case of a 46-year-old woman with breast cancer metastasis in her pituitary. We analyzed 10,347 FDG PET/CT examinations from a tertiary center, finding 4 cases (0.038%) of pituitary metastatic disease from other cancers. We analyzed the differences between SUVmax in cases of physiological high uptake, primary tumor, and hypophysis metastases from other cancers in our database compared with the literature.
Reducing futile acute care services (ACS) for terminally ill cancer patients (Dignity Project).
Authors: Hind Salama, Nashmia Al Mutairi, Moussab Damlaj, Ashwaq Aman Mohammed Alolayan, Ahmed Binahmed, Hagir Salama, Haytham Tlayjeh, Myer Lawrence, Hussam Shehata, Mona Al Shami, Mohammad Alkaiyat, Abdul-Rahman Jazieh
Journal: Journal of Clinical Oncology (2020)

23 Background: Patients with terminal diseases frequently undergo procedures and interventions that are futile and maybe detrimental to the patients’ quality of life. We conducted a quality improvement project aimed to reduce futile acute care services (ACS) for cancer patients treated with a palliative intent. Methods: A multidisciplinary team retrospectively reviewed the records of terminally ill cancer patients who died during in the hospital at our institution, King Abdulaziz Medical City, Riyadh, Saudi Arabia. We included all patients expired between November 2017 to May 2018. The review aimed to assess the magnitude of improper utilization of acute care services (ACS) such as: critical care response team (CCRT), cardio-pulmonary resuscitations (CPR) and admission to intensive care unit (ICU). A root cause analysis and process mapping were conducted to identify reasons for over utilization of these services. Timely documentation of goals of care was identified as a main reason for this problem. Then interventions were implemented to improve the practice. Post intervention data was captured and compared to the baseline data. Results: After delivery of staff education sessions and implementation of mandatory documentation of goals of care in the electronic healthcare record system, the timely documentation of goal of care for patients with palliative intent had significantly increased from 59% of cases in the baseline to 86% for the post intervention phase. As a result, admission to ICU decreased from 32% of cases in the pre intervention phase to 14% in the post intervention phase reducing monthly cost of admission to the ICU by 40% and estimated to be on average of $48,000 USD monthly ($576,000 USD annually). Conclusions: Our interventions resulted in improved documentation of the goal of care leading to decrease in the utilization of acute care services (ACS) including reduction of intensive care unit (ICU) admissions and cost. This outcome is even more relevant nowadays during COVID-19 pandemic and the pressure on critical care resources. Improvement is sustained by integrating the changes in the work process and electronic medical records.