tbuckley/cabot-search huggingface dataset:
Effect of APOE alleles on the glial transcriptome in normal aging and Alzheimer’s disease
Authors: Alberto Serrano-Pozo, Zhaozhi Li, Ayush Noori, Huong N. Nguyen, Aziz Mezlini, Liang Li, Eloise Hudry, Rosemary J. Jackson, Bradley T. Hyman, Sudeshna Das
Journal: Nature Aging (2021)
MA12.05 The Impact of the COVID-19 Pandemic on Post-Operative Outcomes of Thoracic Cancer Surgery in Canada
Authors: C. Huynh, M. Sorin, D. Jones, A. Simone, E. Delic, A. Fazekas, M. Gingrich, C. Anstee, A. Seely, J. Spicer
Journal: Journal of Thoracic Oncology (2021)
Abstract 13103: Application of the Global Registry of Acute Coronary Events (GRACE) and Thrombolysis in Myocardial Infarction (TIMI) Risk Scores in Type 2 Myocardial Infarction
Authors: Sean Murphy, Cian McCarthy, Joshua Cohen, Saad Rehman, Maeve Jones O Connor, David Olshan, Avinainder Singh, Muthiah Vaduganathan, Jinghan Cui, James L Januzzi, Jason Wasfy
Journal: Circulation (2019)

Introduction: The Global Registry of Acute Coronary Events (GRACE) and Thrombolysis in Myocardial Infarction (TIMI) risk scores are validated models providing risk stratification for adverse outcom...
MA08.01 Presence of High-Grade Subtype Predicts Recurrence of Stage I Lung Adenocarcinoma Only in EGFR-Mutated Patients
Authors: J. Ichinose, Y. Kondo, H. Ninomiya, T. Yamamichi, K. Omura, K. Hashimoto, Y. Matsuura, M. Nakao, Y. Ishikawa, S. Okumura, Y. Satoh, M. Mun
Journal: Journal of Thoracic Oncology (2021)
Detection of Neanderthal Adaptively Introgressed Genetic Variants That Modulate Reporter Gene Expression in Human Immune Cells
Authors: Evelyn Jagoda, James R Xue, Steven K Reilly, Michael Dannemann, Fernando Racimo, Emilia Huerta-Sanchez, Sriram Sankararaman, Janet Kelso, Luca Pagani, Pardis C Sabeti, Terence D Capellini
Journal: Molecular Biology and Evolution (2021)

Although some variation introgressed from Neanderthals has undergone selective sweeps, little is known about its functional significance. We used a Massively Parallel Reporter Assay (MPRA) to assay 5,353 high-frequency introgressed variants for their ability to modulate the gene expression within 170 bp of endogenous sequence. We identified 2,548 variants in active putative cis-regulatory elements (CREs) and 292 expression-modulating variants (emVars). These emVars are predicted to alter the binding motifs of important immune transcription factors, are enriched for associations with neutrophil and white blood cell count, and are associated with the expression of genes that function in innate immune pathways including inflammatory response and antiviral defense. We combined the MPRA data with other data sets to identify strong candidates to be driver variants of positive selection including an emVar that may contribute to protection against severe COVID-19 response. We endogenously deleted two CREs containing expression-modulation variants linked to immune function, rs11624425 and rs80317430, identifying their primary genic targets as ELMSAN1, and PAN2 and STAT2, respectively, three genes differentially expressed during influenza infection. Overall, we present the first database of experimentally identified expression-modulating Neanderthal-introgressed alleles contributing to potential immune response in modern humans.
Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study
Authors: Changhoon Yoo, Kyu-pyo Kim, Jae Ho Jeong, Ilhwan Kim, Myoung Joo Kang, Jaekyung Cheon, Byung Woog Kang, Hyewon Ryu, Ji Sung Lee, Kyung Won Kim, Ghassan K Abou-Alfa, Baek-Yeol Ryoo
Journal: The Lancet Oncology (2021)
P71.05 Use of a Multiscale NSCLC Tumor Heterogeneity Model to Predict Tumor Growth Under Gefitinib
Authors: A. L'Hostis, J. Palgen, N. Ceres, E. Peyronnet, A. Perrillat-Mercerot, A. Schneider, M. Margreiter, E. Jacob, R. Kahoul, B. Illigens, M. Hommel, J. Boissel, J. Bosley, C. Monteiro
Journal: Journal of Thoracic Oncology (2021)
Pooling data to assess risks and benefits of discontinuing nucleos(t)ide analogs in patients with chronic hepatitis B: challenges and opportunities
Authors: Yao-Chun Hsu, Cheng-Hao Tseng, Tung-Hung Su, Jia-Horng Kao, Mindie H Nguyen
Journal: Gut (2021)

We read with great interest the meta-analysis by Hall et al ,1 and congratulate the authors on their accomplishment of such a comprehensive literature review. However, we would like to raise a few concerns to caution readers on the study limitations regarding their data aggregation and analysis. First , the analysis included several studies that appeared duplicate considerably in their patient populations and thus similar data from the same patients were counted more than once (table 1).2 For example, four publications from the same study group at the Kaohsiung Chang Gung Memorial Hospital in Taiwan were included to calculate the cumulative incidence of clinical relapse after discontinuation of entecavir or tenofovir. The latest and also largest study by Ma et al 3 presumably contained data from most, if not all, patients enrolled in the three earlier studies. Second , some studies were composed of highly selected participants whose features differed significantly from those of a general population of patients with chronic hepatitis …
P45.07 Real-World Clinically-Relevant Toxicities of ALK TKIs in a Cohort of Patients With Advanced/Metastatic ALK+ NSCLC
Authors: S. Schmid, S. Chotai, S. Cheng, L. Zhan, K. Balaratnam, K. Khan, D. Patel, M.C. Brown, W. Xu, P. Moriarty, O. Kaidanovich-Beilin, F.A. Shepherd, A. Sacher, N. Leighl, P. Bradbury, G. Liu
Journal: Journal of Thoracic Oncology (2021)
Evaluation of vecabrutinib as a model for noncovalent BTK/ITK inhibition for treatment of chronic lymphocytic leukemia
Authors: Billy Michael Chelliah Jebaraj, Annika Müller, Rashmi Priyadharshini Dheenadayalan, Sascha Endres, Philipp M. Roessner, Felix Seyfried, Claudia Walliser, Martin Wist, Jialei Qi, Eugen Tausch, Daniel Mertens, Judith A. Fox, Klaus-Michael Debatin, Lüder Hinrich Meyer, Pietro Taverna, Martina Seiffert, Peter Gierschik, Stephan Stilgenbauer
Journal: Blood (2021)
P60.01 Investigation of Aurora Kinase A as a Potential Biomarker of Radiation in Non-Small Cell Lung Cancer (NSCLC)
Authors: T. Mitchell, T. Jones, S. Danson, M. Glover, J. Bury, J. Horsman, L. Christian, E. Hill, E. Harrison, M. Hatton, H. Bryant
Journal: Journal of Thoracic Oncology (2021)
Epithelial cells remove precancerous cells by cell competition via MHC class I–LILRB3 interaction
Authors: Shiyu Ayukawa, Nagisa Kamoshita, Jun Nakayama, Ryohei Teramoto, Novalia Pishesha, Kenji Ohba, Nanami Sato, Kei Kozawa, Hikari Abe, Kentaro Semba, Nobuhito Goda, Yasuyuki Fujita, Takeshi Maruyama
Journal: Nature Immunology (2021)
Helpful Lessons and Cautionary Tales: How Should COVID-19 Drug Development and Access Inform Approaches to Non-Pandemic Diseases?
Authors: Holly Fernandez Lynch, Arthur Caplan, Patricia Furlong, Alison Bateman-House
Journal: The American Journal of Bioethics (2021)

After witnessing extraordinary scientific and regulatory efforts to speed development of and access to new COVID-19 interventions, patients facing other serious diseases have begun to ask "where's our Operation Warp Speed?" and "why isn't Emergency Use Authorization an option for our health crises?" Although this pandemic bears a number of unique features, the response to COVID-19 offers translatable lessons, in both its successes and failures, for non-pandemic diseases. These include the importance of collaborating across sectors, supporting the highest-priority research efforts, adopting rigorous and innovative trial designs, and sharing reliable information quickly. In addition, the regulatory response to the pandemic demonstrates that lowering standards for marketing authorization can result in increased safety concerns, missed opportunities for research and treatment, and delays in determining what works. Accordingly, policymakers and patient advocates seeking to build on the COVID-19 experience for non-pandemic diseases with unmet treatment needs should focus their efforts on promoting robust and efficient research designs, improving access to clinical trials, and facilitating use of the Food and Drug Administration's existing Expanded Access pathway.
MA07.03 Paired Liquid and Tissues Biopsies to Guide Treatment for Patients That Progress on 2nd Line Osimertinib Treatment
Authors: T. Van Der Wel, M. Jebbink, M.c. Boelens, L. Steinbusch, W. Buikhuisen, W. Theelen, G. Ruiter, J. Burgers, P. Baas, E. Smit, D. Van Den Broek, K. Monkhorst, A.J. De Langen
Journal: Journal of Thoracic Oncology (2021)
P57.08 High Performance Radiomic Classifier to Predict the Response to Immunotherapy in Advanced NSCLC
Authors: G. Mazzaschi, R. Scandino, G. Milanese, C. Pavone, M. Balbi, R. Ledda, R. Minari, F. Trentini, P. Bordi, S. Buti, A. Leonetti, F. Quaini, N. Sverzellati, A. Romanel, M. Tiseo
Journal: Journal of Thoracic Oncology (2021)
P28.03 Durvalumab Adjuvant to Chemoradiation for Patients With Locally Advanced Non-Small Cell Lung Cancer: Real World Experience
Authors: V.D. Haakensen, H.M. Nymoen, C.W. Langberg, H. Horndalsveen, S. Farooqi, M. Bjaanæs, Å. Helland
Journal: Journal of Thoracic Oncology (2021)
OA14.01 Family History of Cancer and Lung Cancer: Information from the Thoracic Tumors Registry (TTR Study)
Authors: V. Calvo, E. Carcereny, D. Rodriguez Abreu, R. Lopez-Castro, M. Guirado, C. Camps, M. Cobo, A.L. Ortega, R. Bernabé, B. Massuti, J. Mosquera, E. Del Barco, J.L. Gonzalez - Larriba, J. Bosch - Barrera, C. Gonzalez Ojeda, M. Domine, O. Juan, M. Martínez-Cutillas, G. Benítez, A. Collazo-Lorduy, M. Cucurull, M. Provencio
Journal: Journal of Thoracic Oncology (2021)
The Polo-like kinase 1 inhibitor onvansertib represents a relevant treatment for head and neck squamous cell carcinoma resistant to cisplatin and radiotherapy
Authors: Anais Hagege, Damien Ambrosetti, Julien Boyer, Alexandre Bozec, Jérôme Doyen, Emmanuel Chamorey, Xingkang He, Isabelle Bourget, Julie Rousset, Esma Saada, Olivia Rastoin, Julien Parola, Frederic Luciano, Yihai Cao, Gilles Pagès, Maeva Dufies
Journal: Theranostics (2021)

Rationale: Head and neck squamous cell carcinoma (HNSCC) represent the 4th most aggressive cancer. 50% of patients relapse to the current treatments combining surgery, radiotherapy and cisplatin and die two years after the diagnosis. Elevated expression of the polo-like kinase 1 (Plk1) correlated to a poor prognosis in epidermoid carcinomas. Methods: The molecular links between Plk1 and resistance to cisplatin/radiotherapy were investigated in patients and cell lines resistant to cisplatin and/or to radiotherapy. The therapeutic relevance of the Plk1 inhibitor onvansertib, alone or combined with cisplatin/radiotherapy, was evaluated on the proliferation/migration on HNSCC cell lines, in experimental HNSCC in mice, in a zebrafish metastasis model and on patient-derived 3D tumor sections. Results: Plk1 expression correlated to a bad prognosis in HNSCC and increased after relapse on cisplatin/radiotherapy. Onvansertib induced mitotic arrest, chromosomic abnormalities and polyploidy leading to apoptosis of sensitive and resistant HNSCC cells at nanomolar concentrations without any effects on normal cells. Onvansertib inhibited the growth of experimental HNSCC in mice and metastatic dissemination in zebrafishes. Moreover, onvansertib combined to cisplatin and/or radiotherapy resulted in a synergic induction of tumor cell death. The efficacy of onvansertib alone and in combination with reference treatments was confirmed on 3D viable sections of HNSCC surgical specimens. Conclusions: Targeting Plk1 by onvansertib represents a new strategy for HNSCC patients at the diagnosis in combination with reference treatments, or alone as a second line treatment for HNCSCC patients experiencing relapses.
Detecting Lynch syndrome in pancreatic ductal adenocarcinoma FNA cytology based on cancer history and immunocytochemistry
Authors: Valentyna Kryklyva, Claudio Luchini, Martijn W J Stommel, Iris D Nagtegaal, Lodewijk A A Brosens
Journal: Gut (2021)

We have read with interest recent articles1–3 about microsatellite instability (MSI) in pancreatic ductal adenocarcinoma (PDAC). Although MSI is rare in PDAC, occurring in only 1%–2% of patients, it is of key importance to recognise in view of a likely better prognosis and responsiveness to immunotherapy.4 In addition, identifying MSI in a tumour may represent the initial step in the recognition of a hereditary form of cancer (Lynch syndrome (LS)), facilitating family screening and surveillance.5 Considering the rarity of MSI in PDAC, the question is how to select patients for MSI testing. Previously, it has been advised to routinely examine specific histological PDAC subtypes (ie, mucinous/colloid and medullary type) for MSI status. With this letter, we underscore the importance of cancer history as another indicator for MSI testing in PDAC.

A 76-year-old patient was diagnosed with PDAC by fine needle aspiration(FNA) cytology (figure 1A). A history of cervical cancer at the age of 48 years was mentioned in the medical record, but the …
Behavioral Intervention for Social Challenges in Children and Adolescents
Authors: Simone J. Darling, Marquelle Goods, Nicholas P. Ryan, Anita K. Chisholm, Kristina Haebich, Jonathan M. Payne
Journal: JAMA Pediatrics (2021)

Social deficits are a common and disabling feature of many pediatric disorders; however, whether behavioral interventions are associated with benefits for children and adolescents with social deficits is poorly understood.
Physician Perspectives on the Effect of Topical Steroid Costs on Patients and Proposed Solutions
Authors: Bina Kassamali, Adam Faletsky, Jane J. Han, Karen Lee, Christina Lopez, Michelle S. Lee, Lourdes M. Pérez-Chada, Arash Mostaghimi, Avery Lachance
Journal: JAMA Dermatology (2021)

Rising costs of topical steroids have increased overall health care and patient out-of-pocket costs while increasing administrative burden on dermatologists and office staff.To explore factors affecting the decision-making process for dermatologists around topical steroid prescriptions, determine the association of insurance coverage and cost, and assess willingness to implement solutions to decrease out-of-pocket topical steroid costs for patients.This qualitative study was conducted from June to November 2020 and used semistructured interviews of 16 dermatologists who reflected a mix of physicians in academic, nonacademic, and private practice until thematic saturation was reached. Each interview was independently coded by 2 researchers. Code frequency and interrater reliability were determined using NVIVO software. Data analysis was conducted from November 2020 to March 2021.Factors influencing dermatologist decision-making around topical steroid selection, outcomes of unaffordable medications on patients, solution recommendations, and perspectives on a system to automatically substitute topical steroid for cheaper alternatives of the same class and vehicle.Of the 16 dermatologists, 8 (50.0%) were women, 8 (50.0%) were men, 1 (6.3%) was Asian, 2 (12.5%) were Latinx, and 12 (75.0%) were White. The interrater reliability ranged from κ = 0.86 to κ = 0.98, indicating excellent agreement. Most physicians (13 [81%]) thought about costs regularly when making choices about topical steroids. All physicians identified a scenario in which patients could not obtain medication based on cost. In these cases, 15 (94%) reported that they try to find an alternative medication by calling the pharmacist or insurance company. Despite a desire to consider cost at the time of prescribing, physicians reported not knowing medication costs before prescribing because of the variability of insurance coverage (15 [94%]), lack of transparency (12 [75%]), and fluctuating drug prices (12 [75%]). In addition to affecting patients, 14 physicians (88%) reported that a patient's inability to afford medications increases administrative burden. Physicians suggested that they were open to solutions that focused on increased cost transparency (10 [63%]) and improved electronic health record technologies. Furthermore, 14 (88%) were willing to use a system to allow the substitution of one topical steroid for another of the same class and vehicle.The results of this qualitative study suggest that opacity around drug costs reduces access for patients and is followed by administrative stress for physicians and staff. Dermatologists are receptive to systems that provide greater transparency for drug costs or automate substitution of equivalent cheaper drugs for patients.
Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study
Authors: Anthony V. Moorman, Emilio Barretta, Ellie R. Butler, Eleanor J. Ward, Katie Twentyman, Amy A. Kirkwood, Amir Enshaei, Claire Schwab, Tom Creasey, Daniel Leongamornlert, Elli Papaemmanuil, Pip Patrick, Laura Clifton-Hadley, Bela Patel, Tobias Menne, Andrew K. McMillan, Christine J. Harrison, Clare J. Rowntree, David I. Marks, Adele K. Fielding
Journal: Leukemia (2021)

Abstract Chromosomal abnormalities are established prognostic markers in adult ALL. We assessed the prognostic impact of established chromosomal abnormalities and key copy number alterations (CNA) among 652 patients with B-cell precursor ALL treated on a modern MRD driven protocol. Patients with KMT2A-AFF1 , complex karyotype (CK) and low hypodiploidy/near-triploidy (HoTr) had high relapse rates 50%, 60% &amp; 53% and correspondingly poor survival. Patients with BCR-ABL1 had an outcome similar to other patients. JAK-STAT abnormalities ( CRLF2 , JAK2 ) occurred in 6% patients and were associated with a high relapse rate (56%). Patients with ABL-class fusions were rare (1%). A small group of patients with ZNF384 fusions ( n = 12) had very good survival. CNA affecting IKZF1, CDKN2A/B, PAX5, BTG1, ETV6, EBF1, RB1 and PAR1 were assessed in 436 patients. None of the individual deletions or profiles were associated with survival, either in the cohort overall or within key subgroups. Collectively these data indicate that primary genetic abnormalities are stronger prognostic markers than secondary deletions. We propose a revised UKALL genetic risk classification based on key established chromosomal abnormalities: (1) very high risk: CK, HoTr or JAK-STAT abnormalities; (2) high risk: KMT2A fusions; (3) Tyrosine kinase activating: BCR-ABL1 and ABL-class fusions; (4) standard risk: all other patients.
Mistaken Identity
Authors: Andrew T. Nguyen, Kevin M. Alexander
Journal: JACC CardioOncology (2021)

C ardiac amyloidosis (CA) occurs when amyloid fibrils infiltrate the myocardial interstitium, resulting in stiffened myocardium and a restrictive cardiomyopathy.More than 95% of CA is due to systemic light chain amyloidosis (AL) or transthyretin amyloidosis (ATTR).AL amyloidosis arises from a clonal plasma cell dyscrasia that produces amyloidogenic monoclonal immunoglobulins.These immunoglobulins then misfold and deposit in various organs, such as the heart, kidneys, liver, gastrointestinal tract, and peripheral nerves (1).ATTR amyloidosis arises when transthyretin (2), a liver-derived transporter of thyroid hormone and retinol proteins, undergoes tetramer dissociation, misfolds, and forms amyloid fibrils in various distant organs (3).Differentiating between AL and ATTR amyloidosis is crucial because their respective clinical courses and treatments differ significantly.Delays in diagnosis lead to poorer outcomes as continued amyloid deposition causes further organ dysfunction.Moreover, diagnostic confusion may delay initiation of amyloid-directed treatment.Thus, having a high index of clinical suspicion coupled with appropriate diagnostic sequencing can ensure a timely and accurate diagnosis of CA.We report a case of a patient that highlights the challenges stemming from inappropriate use of 99m technetium pyrophosphate scintigraphy ( 99m Tc-PYP) scanning to diagnose ATTR-CA in a patient with suspected CA and a plasma cell dyscrasia. CASE DESCRIPTIONA 63-year-old man with a history of bilateral carpal tunnel syndrome presented to an outside hospital with dyspnea on exertion, positional lightheadedness, and chest pain.During his first episode of chest pain, he was found to have a mildly elevated troponin I level of 0.23 ng/mL (reference range: 0-0.09 ng/mL).His N-terminal pro-B-type natriuretic peptide level was 510 pg/mL (reference range: <100 pg/mL).An electrocardiogram revealed sinus rhythm, a right bundle branch block, and Q waves in leads II, III, and aVF.An echocardiogram revealed a left ventricular ejection fraction of 55%, bi-atrial enlargement, concentric left ventricular hypertrophy, and grade II diastolic dysfunction.Coronary angiography was negative for obstructive coronary artery disease.The patient was diagnosed with heart failure with preserved ejection fraction secondary to hypertension and was started on furosemide, metoprolol, lisinopril, and spironolactone.However, metoprolol was soon discontinued due to hypotension, and he was subsequently started on midodrine.Despite medical therapy, the patient had multiple outpatient visits and repeat hospitalizations for dyspnea and chest pain.Two years later, the patient underwent a repeat ischemia evaluation.An exercise treadmill test was negative for inducible ischemia but notable for paroxysmal supraventricular tachycardia and rare premature ventricular contractions during exercise.A subsequent Zio Patch (iRhythm Technologies, Inc) study revealed episodes of nonsustained ventricular tachycardia, with the longest lasting 39 beats.A repeat coronary angiogram was again
Effects of the tumour microenvironment on protoporphyrin IX accumulation in glioblastoma
Authors: Paul Walker, Alina Finch, Victoria Wykes, Colin Watts, Dan Tennant
Journal: Neuro-Oncology (2021)

Abstract Aims Glioblastoma is the most common primary brain tumour and has a poor prognosis. Standard clinical intervention involves the resection of the tumour volume, chemotherapy and radiotherapy. However, achieving gross-total resection is challenging due to poorly defined boundaries as a result of tumour infiltration. Fluorescence-guided surgery (FGS) utilises an apparently selective accumulation of protoporphyrin IX (PPIX) that occurs in areas of glioblastoma after systemic administration of the metabolite 5-aminolevulinic acid (5-ALA). We have investigated the metabolic basis for the heterogeneity of the PPIX fluorescent signal, and its implications for glioma biology. Method Using glioblastoma cell lines and patient-derived primary cells, we have monitored the uptake of 5-ALA and conversion to the fluorescent molecule PPIX. Stable isotope tracing coupled with GCMS and LCMS was used to analyse intra- and extracellular metabolite levels arising from exogenous 5-ALA administration under both normoxic (21% O2) and hypoxic (1% O2) conditions. Results Uptake of exogenous 5-ALA from culture media and conversion to PPIX is observed in a time and dose-dependent manner in both normoxia and hypoxia. High levels of PPIX accumulation are associated with reduced cell proliferation despite the majority of the PPIX synthesised not being retained within the tumour cell, but exported into the medium. Under hypoxic conditions, reduced fluorescence is observed as a result of the decrease in oxygen availability likely affecting the oxygen-dependent enzymes. Stable isotope tracing experiments indicate an increase in the glutamine-derived succinate pool in response to exogenous 5-ALA, which is dependent on flux through the heme pathway. Conclusion Our data suggest that different microenvironments within the tumour alter the activity of the heme biosynthetic pathway, resulting in differential fluorescence in glioblastoma. It paves the way by which we could work to alter the glioblastoma microenvironment in order to further improve the use of FGS in guiding surgery across these devastating tumours.