tbuckley/cabot-search huggingface dataset:
Dual Contrast Manganese-Enhanced MRI and Gadolinium Delayed-Enhanced MRI Detect Heterogenous Myocardial Viability in Ischemic Cardiomyopathy
Authors: Yuko Tada, Michelle R. Santoso, Shahriar Heidary, Hiromi Sano, Atsushi Tachibana, Yuka Matsuura, Phillip Harnish, Phillip C. Yang
Journal: JACC. Cardiovascular imaging (2021)
Disposition of Trastuzumab-MCC-[3H] DM1 following a single intravenous dosing in normal Sprague-Dawley rats
Authors: Margaret Kenrick, Elaine Mai, cinthia pastuskovas, Amy Oldendorp, Michael Reich, Thomas zioncheck, Jay Tibbitts, Ben-Quan Shen
Journal: Cancer Research (2007)

1543  Trastuzumab-MCC-DM1 (Herceptin-MCC-DM1, Tmab-MCC-DM1) is a humanized monoclonal antibody (Herceptin®, trastuzumab) conjugated to a maytansanoid cytotoxic drug, DM1, via the stable linker N-succinimidy 4-[N-malemidomethyl] cyclohexane-carboxylate (MCC). PURPOSE: To understand the disposition of this molecule in a pre-clinical model, we have characterized the plasma stability, biodistribution, metabolism and excretion of Tmab-MCC-[3H] DM1 in rats. METHOD: Eighteen female Sprague-Dawley (SD) rats were given a single intravenous dose of Tmab-MCC-[3H] DM1 at 13mg/kg (1326µg/m2 DM1). Following injection, blood samples, selected organs, urine and feces were collected at pre-determined time points. The collected samples were analyzed for (1) total radioactivity, acetonitrile (ACN) soluble and precipitable radioactivity using a liquid scintillation counter (LSC), (2) total antibody and antibody drug conjugate levels using ELISA, and (3) biotransformation using size exclusion HPLC, respectively. RESULTS: Both plasma radioactivity and total Tmab and antibody drug conjugate levels displayed a biphasic disposition profile, which was consistent with previous pharmacokinetic data. Most plasma radioactivity was in the ACN precipitable fraction (~99%), indicating little free [3H] DM1 or [3H] containing metabolites presented in the plasma. There was no obvious formation of low or high molecular weight species in the plasma over the 14-day study period. Among the tissues analyzed, the radioactivity was mostly detected in the plasma. The radioactivity was also found in several highly perfused organs (liver > kidneys > lungs > heart) at relatively low levels compared with plasma. Radioactivity levels in the kidney and thymus remained constant over the first 7 days after dosing, but decreased by day 14 post-dose. The majority of the radioactive dose was found in feces (~63%) in ACN soluble form. A small amount was detected in urine (~2.3%). CONCLUSION: Tmab-MCC-[3H] DM1 had biphasic disposition profile. There was no obvious formation of high or low molecular weight species in the plasma. Low level of radioactivity was distributed to several highly perfused organs with no persistence or accumulation over the study period. The major route of elimination was through the feces as [3H] DM1 or [3H] containing metabolites. These data provide important information regarding the disposition of Tmab-MCC-[3H] DM1 in rats.
FP02.06 Implementation of a Lung Cancer Value-Based Care Framework in a Low and Middle-Income Country Institution
Authors: C. Baldotto, N. Teich, M. Monteiro, P. Aguiar, M.C. Andrade, C. Longo, M. Batista, R. Lima, D. Azevedo, N. Carvalho, P. Andrade, M. Zukin, L.H. Araújo
Journal: Journal of Thoracic Oncology (2021)
Disruption of the NOX5 Gene Aggravates Atherosclerosis in Rabbits
Authors: Gábor L. Petheő, Andrea Kerekes, Máté Mihálffy, Ágnes Donkó, Lilla Bodrogi, Gabriella Skoda, Mónika Baráth, Orsolya Ivett Hoffmann, Zsolt Szeles, Bernadett Balázs, Gábor Sirokmány, Júlia R. Fábián, Zsuzsanna E. Tóth, Ivett Baksa, Imre Kacskovics, László Hunyady, László Hiripi, Zsuzsanna Bősze, Miklós Geiszt
Journal: Circulation Research (2021)
P01.05 Pilot Study of Inhaled Azacitidine in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
Authors: H. Cheng, Y. Zou, C. Shah, N. Fan, T. Bhagat, R. Gucalp, M. Kim, A. Verma, B. Piperdi, S. Spivack, B. Halmos, R. Perez-Soler
Journal: Journal of Thoracic Oncology (2021)
P48.17 Efficacy and Safety of AK104, an Anti-PD-1/CTLA-4 Bispecific Antibody, in a Patient with Large Cell Neuroendocrine Carcinoma of the Lung
Authors: S. Frentzas, K.Y. Kwek, A. Konpa, X. Jin
Journal: Journal of Thoracic Oncology (2021)
FP14.10 Efficacy and Safety of Selpercatinib (LOXO-292) in East Asian Patients with RET Fusion-Positive NSCLC
Authors: H. Loong, K. Goto, K. Park, Y. Ohe, M. Nishio, B.C. Cho, Y.J. Kim, P. French, V. Soldatenkova, D. Tan
Journal: Journal of Thoracic Oncology (2021)
HSR21-073: Febrile Neutropenia Outcomes Among Patients With Breast Cancer and Non-Hodgkin’s Lymphoma Receiving Pegfilgrastim Prophylaxis: A Real-World Analysis of Commercial and Medicare Claims From 2017-2018
Authors: Weijia Wang, Edward Li, Kim Campbell, Ali McBride
Journal: Journal of the National Comprehensive Cancer Network (2021)

"HSR21-073: Febrile Neutropenia Outcomes Among Patients With Breast Cancer and Non-Hodgkin’s Lymphoma Receiving Pegfilgrastim Prophylaxis: A Real-World Analysis of Commercial and Medicare Claims From 2017-2018" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Alterations in the Global Proteome and Phosphoproteome in Third Generation EGFR TKI Resistance Reveal Drug Targets to Circumvent Resistance
Authors: Xu Zhang, Tapan K. Maity, Karen E. Ross, Yue Qi, Constance M. Cultraro, Meriam Bahta, Stephanie Pitts, Meghana Keswani, Shaojian Gao, Khoa Dang P. Nguyen, Julie Cowart, Fatos Kirkali, Cathy Wu, Udayan Guha
Journal: Cancer Research (2021)

Abstract Lung cancer is the leading cause of cancer mortality worldwide. The treatment of patients with lung cancer harboring mutant EGFR with orally administered EGFR tyrosine kinase inhibitors (TKI) has been a paradigm shift. Osimertinib and rociletinib are third-generation irreversible EGFR TKIs targeting the EGFR T790M mutation. Osimertinib is the current standard of care for patients with EGFR mutations due to increased efficacy, lower side effects, and enhanced brain penetrance. Unfortunately, all patients develop resistance. Genomic approaches have primarily been used to interrogate resistance mechanisms. Here we characterized the proteome and phosphoproteome of a series of isogenic EGFR-mutant lung adenocarcinoma cell lines that are either sensitive or resistant to these drugs, comprising the most comprehensive proteomic dataset resource to date to investigate third generation EGFR TKI resistance in lung adenocarcinoma. Unbiased global quantitative mass spectrometry uncovered alterations in signaling pathways, revealed a proteomic signature of epithelial–mesenchymal transition, and identified kinases and phosphatases with altered expression and phosphorylation in TKI-resistant cells. Decreased tyrosine phosphorylation of key sites in the phosphatase SHP2 suggests its inhibition, resulting in subsequent inhibition of RAS/MAPK and activation of PI3K/AKT pathways. Anticorrelation analyses of this phosphoproteomic dataset with published drug-induced P100 phosphoproteomic datasets from the Library of Integrated Network-Based Cellular Signatures program predicted drugs with the potential to overcome EGFR TKI resistance. The PI3K/MTOR inhibitor dactolisib in combination with osimertinib overcame resistance both in vitro and in vivo. Taken together, this study reveals global proteomic alterations upon third generation EGFR TKI resistance and highlights potential novel approaches to overcome resistance. Significance: Global quantitative proteomics reveals changes in the proteome and phosphoproteome in lung cancer cells resistant to third generation EGFR TKIs, identifying the PI3K/mTOR inhibitor dactolisib as a potential approach to overcome resistance.
Covid-19: Stronger warnings are needed to curb socialising after vaccination, say doctors and behavioural scientists
Authors: Michael Day
Journal: BMJ (2021)

Experts have called for stronger health warnings for people being vaccinated against covid-19 after observing a rise in infections shortly after vaccination, suggesting that many people are letting their guard down before the vaccine has taken effect.

Earlier this month a study led by Public Health England of vaccination in the over 70s found a “notable” rise in covid-19 infections in people immediately after they received the Pfizer-BioNTech or AstraZeneca vaccine.1 Similarly, a study of Israel’s vaccination programme, reported in February, found a similar spike in cases among people who had just been jabbed.2 It found that daily incidence approximately doubled after vaccination until about day 8.

A survey by the UK’s Office for National Statistics, looking at coronavirus and vaccine attitudes and behaviours in England in February,3 shows why these spikes may be happening. Among over 80s who had received …
Advanced bandages for diabetic wound healing
Authors: Simon Matoori, Aristidis Veves, David J. Mooney
Journal: Science Translational Medicine (2021)

Current treatment options for foot ulcers, a serious and prevalent complication of diabetes, remain nonspecific. In this Perspective, we present recent advances in understanding the pathophysiology of diabetic wound healing and the emergence of previously unidentified targets. We discuss wound dressings tailored to the diabetic wound environment currently under development.
OA06.03 Patient-Reported Outcomes from ADAURA: Osimertinib as Adjuvant Therapy in Patients with Resected EGFR Mutated (EGFRm) NSCLC
Authors: M. Majem, J. Goldman, T. John, C. Grohe, K.K. Laktionov, S. Kim, T. Kato, H.V. Vu, S. Lu, K.Y. Lee, C. Akewanlop, C. Yu, F. De Marinis, L. Bonanno, M. Domine, F. Shepherd, L. Zeng, D. Kulkarni, N. Medic, M. Tsuboi, R. Herbst, Y. Wu
Journal: Journal of Thoracic Oncology (2021)
Abstract 16204: The Use of a Novel Suture Material in Cardiac Device Implantation
Authors: Emi Nakano
Journal: Circulation (2020)

Background: Cardiac implantable electric device (CIED) implantation is a minor surgical procedure. One post-surgery complication often experienced is a suture knot projecting out of the skin 1-3 months after surgery. A unidirectional barbed suture (V-Loc; Covidien, Mansfield, MA) is a suture with barbs, which enables securing sutures without knots. The conventional sutures often leave a knot protruding at the suture line end; however, V-Loc eliminates the need to tie surgical knots and leaves a clean surface. Objective: We aimed to evaluate the safety and efficacy of V-Loc use in CIED implantation. Methods: A total of 153 patients underwent CIED implantation. Eighty-one patients were sutured using conventional string (PDS; Ethicon, Somerville, NJ) and V-Loc was used in 72 cases. A conventional method is to close a wound in three layers. After approximating the subcutaneous tissue in two layers with 3/0 PDS, the skin was closed with 4/0 PDS. Meanwhile, the new technique involves an over-and-over running stitch on the subcutaneous tissue with 3/0 V-Loc, followed by skin closure with 4/0 V-Loc. Results: The average suturing time was shorter in the V-Loc group than in the conventional group (9.9±1.7 vs. 18.0±4.1 mins. P&lt;0.01). This translated to a reduction in closure time by 45% (8.1 mins) without complications such as wound infection and dehiscence. In the conventional group, 16 of 81 patients (19.8%) had a suture knot projecting out without infection. Conclusion: V-loc suture material offers the possibility of a knotless stitch. We noted positive results in patients who were sutured with V-loc, and suggest its usefulness in CIED implantation.
P75.03 KEYNOTE-U01: A Phase 2 Umbrella Study of Investigational Agents Plus Pembrolizumab-Based Therapy for Advanced NSCLC
Authors: S. Rao, S. Arnold, D. Carbone, R. Salgia, A. Tsao, J. Niu, C. Aggarwal, K.H. Dragnev, M. Awad, J. Gainor, M. Gubens, V. Velcheti, L. Telliho, O.O. Akala, E. Chartash, J. Stevenson
Journal: Journal of Thoracic Oncology (2021)
Characteristics and outcomes of therapy-related myeloid neoplasms following autologous stem cell transplantation for multiple myeloma
Authors: Kalyan Nadiminti, M. Hasib Sidiqi, Kapil Meleveedu, Hassan B. Alkhateeb, William J. Hogan, Mark Litzow, Mrinal Patnaik, Shaji Kumar, Morie Gertz, Dong Chen, Mithun Vinod Shah
Journal: Blood Cancer Journal (2021)

Advances over the last two decades have resulted in a significant improvement in survival of patients with multiple myeloma (MM)-primarily driven by the emergence of immunomodulators (IMiDs), proteasome inhibitors (PI) and monoclonal antibodies.Despite these improvements, high-dose melphalan (HDM)-based autologous stem cell transplantation (SCT) followed by lenalidomide maintenance remains part of standard initial therapy for transplant-eligible patients 1 .The development of therapyrelated myeloid neoplasms (t-MN) is an uncommon, but dreadful complication with considerable morbidity and poor survival.While the exposure to melphalan and autologous SCT are known risk factors 2,3 , the impact of lenalidomide, in the setting of HDM, is less clear 4-7 .Autologous SCT followed by lenalidomide maintenance leads to an improved progression-free-and overall survival, making it the de facto standard for eligible patients 5,6 .We studied the incidence of t-MN in post-SCT MM patients in the era of novel therapies and studied the impact of lenalidomide exposure on the risk of t-MN post-SCT.We also analyzed factors that may impact outcomes after t-MN diagnosis.We identified MM patients that underwent autologous SCT following HDM (1998-2016) and subsequently developed t-MN as defined by the 2016 World Health Organization classification.Complex and monosomal karyotype (CK and MK respectively) were defined according to the 1995 International System for Human Cytogenetic
P64.01 MiRNAs in Exosomes Isolated From the Blood of Non-Small Cell Lung Cancer Patients: Biomarkers for Lung Cancer Prediction and Prognosis
Authors: G. Lan, W. Wang, Z. Zhai, X. Li, H. Chen, L. Huang, Y. Zhu, K. Du, C. Xu
Journal: Journal of Thoracic Oncology (2021)
P24.07 Nivolumab and Ipilimumab +/- UV1 Vaccination as 2nd Line Treatment in Patients with Malignant Mesothelioma (the NIPU-Study)
Authors: V. Haakensen, A. Nowak, E. Ellingsen, O. Grundberg, S. Farooqi, T. Mcculloch, S. Cedres, M. Bjaanæs, Å. Helland
Journal: Journal of Thoracic Oncology (2021)
Abstract 194: Effects of PEG-20k on Coronary Perfusion Pressure and Post-Resuscitation Myocardial and Cerebral Function in a Rat Model of Cardiac Arrest
Authors: Weiwei Ge, Christine Moore, Guanghui Zheng, Xianfei Ji, Fenglian He, Juntao Hu, Jennifer Bradley, Mary Ann A Peberdy, Joseph P Ornato, Martin Mangino, Wanchun Tang
Journal: Circulation (2019)

Introduction: Epinephrine is the primary drug given during cardiopulmonary resuscitation (CPR), when given early, to reverse cardiac arrest (CA) by stimulation of α-adrenergic receptors in vascular smooth muscle. This increases coronary perfusion pressure (CPP) and increases rate of return of spontaneous circulation (ROSC). However, the use of epinephrine is not associated with a significant difference in long-term survival or favorable neurologic outcome when given late after arrest onset. In the present study, we compared the effects of aortic injection of polyethylene glycol-20k (PEG-20k) vs. epinephrine during CPR on CPP and postresuscitation myocardial and cerebral function in a rat model of CA. Hypothesis: Aortic injection of PEG-20k during CPR will increase CPP to the same extent as epinephrine without adversely affecting post-resuscitation myocardial and cerebral function. Methods: Twenty four male Sprague-Dawley rats weighing between 450-550 g were randomized into four groups: 1) PEG-20k 2) epinephrine 3) saline placebo 4) saline-intra-aorta (IA). Eight minutes of CPR was initiated after 6 minutes of untreated ventricular fibrillation. PEG-20k IA (10% est. total blood volume [1.8ml]), saline IA, saline IV or epinephrine IV (20ug/kg) was given after 4 minutes of CPR by continuous infusion over 3 minutes. CPP was recorded continuously and resuscitation was attempted with 4 Joule defibrillation. Myocardial function was measured at baseline, 2, 4, and 6 hours after ROSC by echocardiography and neurologic deficit scores (NDS) were recorded at 24, 48, and 72 hours after ROSC. Results: In both saline groups, CPP did not change. However, aortic injection of PEG-20k increased CPP significantly to the same extent as epinephrine (Fig 1). Post-resuscitation ejection fraction was significantly greater in PEG-20k compared to epinephrine (64 + 1 vs 45 + 3, p&lt;0.05) and NDS was significantly improved in PEG-20k compared to epinephrine (100 + 50 vs 450 + 50, p&lt;0.05).
Clinical Impact of Presurgery Circulating Tumor DNA after Total Neoadjuvant Treatment in Locally Advanced Rectal Cancer: A Biomarker Study from the GEMCAD 1402 Trial
Authors: Joana Vidal, David Casadevall, Beatriz Bellosillo, Carles Pericay, Rocio Garcia-Carbonero, Ferran Losa, Laia Layos, Vicente Alonso, Jaume Capdevila, Javier Gallego, Ruth Vera, Antonieta Salud, Marta Martin-Richard, Miguel Nogué, Elena Cillán, Joan Maurel, Iris Faull, Victoria Raymond, Carlos Fernández-Martos, Clara Montagut
Journal: Clinical Cancer Research (2021)

Total neoadjuvant treatment (TNT) is a valid strategy for patients with high-risk locally advanced rectal cancer (LARC). Biomarkers of response to TNT are an unmet clinical need. We aimed to determine the value of circulating tumor DNA (ctDNA) to predict tumor response, recurrence, and survival in patients with LARC treated with TNT.The GEMCAD 1402 was a phase II randomized, multicentric clinical trial that randomized 180 patients with LARC to modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) +/- aflibercept, followed by chemoradiation and surgery. Plasma samples were collected at baseline and after TNT within 48 hours before surgery (presurgery). An ultrasensitive assay that integrates genomic and epigenomic cancer signatures was used to assess ctDNA status. ctDNA results were correlated with variables of local tumor response in the surgery sample, local/systemic recurrence, and survival.A total of 144 paired plasma samples from 72 patients were included. ctDNA was detectable in 83% of patients at baseline and in 15% following TNT (presurgery). No association was found between ctDNA status and pathologic response. Detectable presurgery ctDNA was significantly associated with systemic recurrence, shorter disease-free survival (HR, 4; P = 0.033), and shorter overall survival (HR, 23; P < 0.0001).In patients with LARC treated with TNT, presurgery ctDNA detected minimal metastatic disease identifying patients at high risk of distant recurrence and death. This study sets the basis for prospective clinical trials that use liquid biopsy to personalize the therapeutic approach following TNT.
P76.69 Real-World Effectiveness of EGFR TKI First-Line Treatment of Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer in US
Authors: S. Gautam, L. Herms, L. Bartolome, M. Pastel, K. Wilner, M. Fisher, J. Ivanova
Journal: Journal of Thoracic Oncology (2021)
Outcome of a Change in Allocation of Livers for Transplant in the United States
Authors: Kyle H. Sheetz, Seth A. Waits
Journal: JAMA Surgery (2021)

On February 4, 2020, the Organ Procurement and Transplant Network and United Network for Organ Sharing (UNOS) implemented a new policy for allocating donor livers for transplant.The policy moves away from a donor service area-based allocation model and instead focuses on radially oriented zones (acuity circles) around potential donors.Its goals are to improve access to transplant for the candidates with the greatest urgency, increase the number of pediatric transplants, and reduce waitlist mortality. 1However, there are also concerns that it may reduce access for socioeconomically disadvantaged groups (eg, patients in rural areas) and significantly increase travel burden for liver recovery. [2]3][4] Using data from UNOS, we assessed whether implementation of the policy was associated with immediate changes in the distance traveled for recovery or the proportion of organ imports or exports by UNOS regions.Methods | We identified all accepted liver offers from deceased donors between January 3 and March 3, 2020 (prior to dramatic changes in practice because of the coronavirus disease 2019 pandemic).We collected data regarding donation after brain vs circulatory death, location of the donor and recipient hospitals, and the UNOS regions of both the donor and recipient.Our primary outcomes were the distance between
OA07.08 HUDSON: An Open-Label, Multi-Drug, Biomarker-Directed, Phase II Platform Study in Patients with NSCLC, who Progressed on Anti-PD(L)1 Therapy
Authors: B. Besse, M. Awad, P. Forde, M. Thomas, K. Park, G. Goss, N. Rizvi, F. Huemer, M. Hochmair, J. Bennouna, J. Cosaert, Z. Szucs, P. Mortimer, R. Hobson, K. Sachsenmeier, E. Dean, H. Ambrose, C. Hayward, M. Dressman, S. Barry, J. Heymach
Journal: Journal of Thoracic Oncology (2021)
Single Coronary Artery Anomaly as a Different Ethiological Variant of Myocardial Ischemia
Authors: Viktoria Dimitrova
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

The single coronary artery is а rare congenital disorder, a subset of coronary artery anomalies. The clinical presentation varies from asymptomatic to malignant variants and is usually diagnosed during coronary angiography or post-mortem examinations. It may or may not be associated with another congenital heart disease. During the three years period and based on clinical indications, we performed selective coronary angiography of 7,996 patients. We discovered five clinical cases of a single coronary artery, which complies with the frequency of this anomaly 0.06% of the study population. All five clinical cases had moderate left ventricular systolic dysfunction and four of them had sinus rhythm disturbances – supraventricular cardiac arrhythmias or sinus tachycardia. Anomalous coronary anatomy may result in insufficient flow delivery even without coronary obstruction. It is important to specify the course of the ectopic artery. Cardiac ischemia could explain left ventricular systolic dysfunction and rhythm disorders. Significant coronary artery disease had three of them. The main goals of this research are to detect the frequency of single coronary artery anomaly among studied population, to illustrate the variety of clinical presentation of this disorder, related to anatomical variants of the anomaly, and to choose the most appropriate treatment decision, based on the present experience.
New agency will focus on preparing and protecting UK from future pandemics
Authors: Adrian O’Dowd
Journal: BMJ (2021)

The government has unveiled its new body—the UK Health Security Agency (UKHSA) —with the specific remit of preparing the UK for future pandemics such as covid-19.

The agency will start its work next month and be fully operational by the autumn to lead on protecting the UK against future external health threats such as infectious diseases. Its primary focus will be the continued fight against the covid-19 pandemic and it will be led by England’s deputy chief medical officer Jenny Harries.

This body was originally announced in August last year as the National Institute for Health Protection when the government confirmed that it was closing Public Health England (PHE) and merging its …
Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients
Authors: Brian J. Boyarsky, William A. Werbel, Robin K. Avery, Aaron A. R. Tobian, Allan B. Massie, Dorry L. Segev, Jacqueline M. Garonzik-Wang
Journal: JAMA (2021)

This study quantifies antispike protein antibody responses to first-dose messenger RNA (mRNA) COVID-19 vaccines in solid organ transplant recipients to better understand the immunogenicity of the vaccines in immunocompromised individuals.