tbuckley/cabot-search huggingface dataset:
Effect of minor amounts of β-calcium pyrophosphate and hydroxyapatite on the physico-chemical properties and osteoclastic resorption of β-tricalcium phosphate cylinders
Authors: B. Le Gars Santoni, L. Niggli, S. Dolder, O. Loeffel, G.A. Sblendorio, R. Heuberger, Y. Maazouz, C. Stähli, N. Döbelin, P. Bowen, W. Hofstetter, M. Bohner
Journal: Bioactive Materials (2021)

β-Tricalcium Phosphate (β-TCP), one of the most used bone graft substitutes, may contain up to 5 wt% foreign phase according to standards. Typical foreign phases include β-calcium pyrophosphate (β-CPP) and hydroxyapatite (HA). Currently, the effect of small amounts of impurities on β-TCP resorption is unknown. This is surprising since pyrophosphate is a very potent osteoclast inhibitor. The main aim of this study was to assess the effect of small β-CPP fractions (<1 wt%) on the in vitro osteoclastic resorption of β-TCP. A minor aim was to examine the effect of β-CPP and HA impurities on the physico-chemical properties of β-TCP powders and sintered cylinders. Twenty-six batches of β-TCP powder were produced with a Ca/P molar ratio varying between 1.440 and 1.550. Fifteen were further processed to obtain dense and polished β-TCP cylinders. Finally, six of them, with a Ca/P molar ratio varying between 1.496 (1 wt% β-CPP) and 1.502 (1 wt% HA), were incubated in the presence of osteoclasts. Resorption was quantified by white-light interferometry. Osteoclastic resorption was significantly inhibited by β-CPP fraction in a linear manner. The presence of 1% β-CPP reduced β-TCP resorption by 40%, which underlines the importance of controlling β-CPP content when assessing β-TCP biological performance.
One in 10 UK adults could have diabetes by 2030, warns charity
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Up to one in 10 adults in the UK could have diabetes by 2030 unless the government makes a substantial investment in prevention services, a charity has warned.

Diagnoses of diabetes have doubled over the past 15 years, and there are currently almost 4.1 million people in the UK who have either type 1 or type 2 diabetes. Around 90% have type 2, of which key risk factors are obesity and high blood pressure. Diabetes UK forecasts that this number could rise to 5.5 million if current trends continue and warned of a “public health emergency” …
A Novel Long Noncoding RNA Finetunes the DNA Damage Response in Hepatocellular Carcinoma
Authors: Marina Barcena-Varela, Amaia Lujambio
Journal: Cancer Research (2021)

Abstract The study by Unfried and colleagues reports the intriguing discovery of a novel long noncoding RNA (lncRNA) with a critical role in the regulation of DNA damage response in hepatocellular carcinoma. Providing an exhaustive and detailed characterization of the complex network interactions within the double-stranded breaks in the DNA, the authors demonstrated that NIHCOLE serves as a scaffold and facilitator of nonhomologous end-joining machinery. This study greatly contributes to the growing evidence supporting the key roles of ncRNAs in health and disease. Although larger studies are needed to understand the potential of lncRNAs to improve the clinical management of patients with cancer, this study demonstrates that high expression of NIHCOLE may be associated with an impaired response to DNA damage–based therapies, in part through its role in preventing cell death. See related article by Unfried et al., p. 4910
914P Impact of induction chemotherapy (ICT) in borderline resectable or unresectable locally advanced oral squamous cell carcinoma (OSCC)
Authors: D. Kukreja, D. Chakrabarti, A.V. Resu, M. Verma, S. Qayoom, S. Rajan, N. Akhtar, R. Gupta, M.L.B. Bhatt
Journal: Annals of Oncology (2021)
530P Phase II study of PI3K inhibitor copanlisib in cancer patients with deleterious PTEN mutations and retained PTEN protein expression: Results from the NCI-MATCH Trial (EAY131) sub-protocol Z1H
Authors: F. Janku, Z. Wei, M.A. Davies, E.P. Mitchell, J.J. Wright, L.A. Doyle, R.J. Gray, V. Wang, L.M. McShane, L.V. Rubinstein, D.R. Patton, P.M. Williams, S.R. Hamilton, B. Conley, C.L. Arteaga, L.N. Harris, P.J. O'Dwyer, A.P. Chen, K.T. Flaherty
Journal: Annals of Oncology (2021)
Remdesivir induces persistent mitochondrial and structural damage in human induced pluripotent stem cell-derived cardiomyocytes
Authors: Maxwell Kwok, Carrie Lee, Hung Sing Li, Ruixia Deng, Chantelle Tsoi, Qianqian Ding, Suk Ying Tsang, Kam Tong Leung, Bryan P Yan, Ellen N Poon
Journal: Cardiovascular Research (2021)

Remdesivir is a prodrug of an adenosine triphosphate analogue and is currently the only drug formally approved for the treatment of hospitalized coronavirus disease of 2019 (COVID-19) patients. Nucleoside/nucleotide analogues have been shown to induce mitochondrial damage and cardiotoxicity, and this may be exacerbated by hypoxia, which frequently occurs in severe COVID-19 patients. Although there have been few reports of adverse cardiovascular events associated with remdesivir, clinical data are limited. Here, we investigated whether remdesivir induced cardiotoxicity using an in vitro human cardiac model.Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to remdesivir under normoxic and hypoxic conditions to simulate mild and severe COVID-19, respectively. Remdesivir induced mitochondrial fragmentation, reduced redox potential, and suppressed mitochondrial respiration at levels below the estimated plasma concentration under both normoxic and hypoxic conditions. Non-mitochondrial damage such as electrophysiological alterations and sarcomere disarray were also observed. Importantly, some of these changes persisted after the cessation of treatment, culminating in increased cell death. Mechanistically, we found that inhibition of DRP1, a regulator of mitochondrial fission, ameliorated the cardiotoxic effects of remdesivir, showing that remdesivir-induced cardiotoxicity was preventable and excessive mitochondrial fission might contribute to this phenotype.Using an in vitro model, we demonstrated that remdesivir can induce cardiotoxicity in hiPSC-CMs at clinically relevant concentrations. These results reveal previously unknown potential side-effects of remdesivir and highlight the importance of further investigations with in vivo animal models and active clinical monitoring to prevent lasting cardiac damage to patients.
Hepatic Sensing Loop Regulates PCSK9 Secretion in Response to Inhibitory Antibodies
Authors: Carlota Oleaga, Michael D. Shapiro, Joshua Hay, Paul A. Mueller, Joshua Miles, Cecilia Huang, Emily Friz, Hagai Tavori, Peter P. Toth, Cezary Wójcik, Bruce A. Warden, Jonathan Q. Purnell, P. Barton Duell, Nathalie Pamir, Sergio Fazio
Journal: Journal of the American College of Cardiology (2021)

Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9i) lower LDL-C by up to 60% and increase plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels by 10-fold.
554P Phase I clinical trial of OBP-301, a novel telomerase-specific oncolytic virus, in combination with radiotherapy in esophageal cancer patients
Authors: S. Tanabe, T. Kojima, H. Tazawa, K. Noma, K. Katsui, K. Hori, N. Nakamura, Y. Urata, T. Doi, S. Kanazawa, Y. Shirakawa, T. Fujiwara, H. Okada
Journal: Annals of Oncology (2021)
Abstract 14971: A Report of Real-World Incidence of Atrial Arrhythmia in Heart Failure Patients After Applying AdaptivCRT Algorithm
Authors: Maurizio Lunati, David O’Donnell, Shelby Li, Pascal Smeets, Yong-Mei Cha, Jagmeet Singh
Journal: Circulation (2018)

Introduction: Atrial Fibrillation (AF) is a common comorbidity for heart failure patients. The AdaptivCRT algorithm provides synchronized left-ventricular pacing in patients with normal PR interval...
Eosinophilic features in clear cell renal cell carcinoma correlate with outcomes of immune checkpoint and angiogenesis blockade
Authors: Takashi Yoshida, Chisato Ohe, Junichi Ikeda, Naho Atsumi, Haruyuki Ohsugi, Motohiko Sugi, Koichiro Higasa, Ryoichi Saito, Koji Tsuta, Tadashi Matsuda, Hidefumi Kinoshita
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Clear cell renal cell carcinoma (ccRCC) displays heterogeneity in appearance—a distinctive pale clear to eosinophilic cytoplasm; however, little is known about the underlying mechanisms and clinical implications. We investigated the role of these eosinophilic features in ccRCC on oncological outcomes and response to tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Methods One-hundred and thirty-eight ccRCC cases undergoing radical surgery (cohort 1) and 54 metastatic ccRCC cases receiving either TKIs or ICIs (cohort 2) were included. After histological evaluation, all cases were divided into three phenotypes based on the eosinophilic features at the highest-grade area: clear, mixed, or eosinophilic type. Gene expression and immunohistochemical analyses were performed to explore the potential mechanisms of these phenotypes in cohort 1. Further, the association of the three phenotypes with the best objective response to TKI or ICI, clinical benefit (complete/partial response or stable disease), and overall survival (OS) was assessed in cohort 2. Results The clear type was significantly associated with increased hypoxia as well as angiogenesis gene signatures compared with the eosinophilic type. Gene signatures and protein expression related to effector T cell and immune checkpoint molecules were elevated to a greater extent in the eosinophilic type, followed by the mixed and clear types. The mixed and eosinophilic types exhibited greater PBRM1-negativity and increased prevalence of the epithelial-mesenchymal transition gene signature than the clear type. In the mixed/eosinophilic types of cohort 2, significant clinical benefit was observed in the ICI therapy group versus the TKI therapy group (p=0.035), and TKI therapy vs ICI therapy was an independent factor for worse prognosis of OS (HR 3.236; p=0.012). Conclusion The histological phenotype based on the eosinophilic features, which are linked to major immunological mechanisms of ccRCC, was significantly correlated with therapeutic efficacy.
986P Antitumor effect of zolbetuximab combined with chemotherapeutic agents or an anti-mPD-1 antibody in syngeneic immune-competent mice
Authors: T. Nishibata, J. Weng, K. Omori, Y. Sato, T. Nakazawa, T. Suzuki, T. Yamada, I. Nakajo, F. Kinugasa, T. Yoshida
Journal: Annals of Oncology (2021)
426P Spotlight on refractory metastatic colorectal cancer (refMCRC): Role of prognostic characteristics in the continuum of care
Authors: A.A. Valdivia, F. Salva, J. Ros, I. Baraibar, G. Argiles Martinez, N. Saoudi Gonzalez, A. Garcia, N. Mulet Margalef, J.L. Cuadra Urteaga, J. Capdevila, M.A. Salud Salvia, D. Paez, E. Casado, R. Comas, F. Ruiz-Pace, G. Villacampa Javierre, D.A. Acosta Eyzaguirre, R. Dienstmann, M.E. Elez Fernandez, J. Tabernero
Journal: Annals of Oncology (2021)
Secondary analysis of malaria rapid diagnostic tests from rounds 5–8 of WHO product testing with a focus on false-negative results
Authors: Biao Xu, Bo Tu, Fang Chu, Mohamed Jalloh, Jin-Song Mu, Jun-Jie Zheng, Wei-Wei Chen
Journal: Military Medical Research (2021)

Abstract Despite the widespread use of malaria rapid diagnostic test (RDT) in clinical practice, there are a lot of challenges. We conducted a secondary analysis of 129 malaria RDT data from rounds 5–8 of the World Health Organization (WHO) product testing summary and discuss the causes of false-negative (FN) results with a focus on low parasite density, improper RDT storage, operation and interpretation, and plasmodium falciparum with a pfhrp2/3 gene deletion. The results demonstrated that the malaria RDTs currently commercially available might cause FN results in practice.
The Safety and Immunologic Effectiveness of the Live Varicella-Zoster Vaccine in Patients Receiving Tumor Necrosis Factor Inhibitor Therapy
Authors: Jeffrey R. Curtis, Stacey S. Cofield, S. Louis Bridges, John Bassler, Atul Deodhar, Theresa L. Ford, Joseph Huffstutter, Allen Jankeel, Alan Kivitz, Shaila Kamal, Stephen Lindsey, Ilhem Messaoudi, Norma Mendoza, Kaleb Michaud, Ted R. Mikuls, David Ridley, William Shergy, Sarah A.R. Siegel, Kevin L. Winthrop
Journal: Annals of Internal Medicine (2021)

Background: The safety and effectiveness of live virus vaccines, such as the varicella-zoster vaccine, are unknown in patients with inflammatory diseases receiving immunomodulatory therapy such as tumor necrosis factor inhibitors (TNFis). Objective: To evaluate the safety and immunogenicity of the live attenuated zoster vaccine (ZVL) in patients receiving TNFis. Design: Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02538341) Setting: Academic and community-based rheumatology, gastroenterology, and dermatology practices. Patients: Adults aged 50 years or older receiving TNFis for any indication. Intervention: Random assignment to ZVL versus placebo. Measurements: Glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells measured at baseline and 6 weeks after vaccination. Suspected varicella infection or herpes zoster was clinically assessed using digital photographs and polymerase chain reaction on vesicular fluid. Results: Between March 2015 and December 2018, 617 participants were randomly assigned in a 1:1 ratio to receive ZVL (n = 310) or placebo (n = 307) at 33 centers. Mean age was 62.7 years (SD, 7.5); 66.1% of participants were female, 90% were White, 8.2% were Black, and 5.9% were Hispanic. The most common TNFi indications were rheumatoid arthritis (57.6%) and psoriatic arthritis (24.1%); TNFi medications were adalimumab (32.7%), infliximab (31.3%), etanercept (21.2%), golimumab (9.1%), and certolizumab (5.7%). Concomitant therapies included methotrexate (48.0%) and oral glucocorticoids (10.5%). Through week 6, no cases of confirmed varicella infection were found; cumulative incidence of varicella infection or shingles was 0.0% (95% CI, 0.0% to 1.2%). At 6 weeks, compared with baseline, the mean increases in geometric mean fold rise as measured by gpELISA and ELISpot were 1.33 percentage points (CI, 1.17 to 1.51 percentage points) and 1.39 percentage points (CI, 1.07 to 1.82 percentage points), respectively. Limitation: Potentially limited generalizability to patients receiving other types of immunomodulators. Conclusion: This trial informs safety concerns related to use of live virus vaccines in patients receiving biologics. Primary Funding Source: The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology.
690P Comprehensive genomic profiling (CGP) of VHL mutated and VHL wild type clear cell renal cell carcinoma (ccRCC)
Authors: G. Bratslavsky, P. Grivas, P.E. Spiess, B. Decker, N.A. Danziger, E. Sokol, J.S. Ross
Journal: Annals of Oncology (2021)
Safety, Immunogenicity and Interchangeability of Biosimilar Monoclonal Antibodies and Fusion Proteins: A Regulatory Perspective
Authors: Pekka Kurki, Sean Barry, Ingrid Bourges, Panagiota Tsantili, Elena Wolff-Holz
Journal: Drugs (2021)

Biosimilars have been used for 15 years in the European Union (EU), and have been shown to reduce costs and increase access to important biological medicines. In spite of their considerable exposure and excellent safety record, many prescribers still have doubts on the safety and interchangeability of biosimilars, especially monoclonal antibodies (mAbs) and fusion proteins.The aim of this study was to analyse the short- and long-term safety and interchangeability data of biosimilar mAbs and fusion proteins to provide unbiased information to prescribers and policy makers.Data on the safety, immunogenicity and interchangeability of EU-licensed mAbs and fusion proteins were examined using European Public Assessment Reports (EPARs) and postmarketing safety surveillance reports from the European Medicines Agency (EMA). As recent biosimilar approvals allow self-administration by patients by the subcutaneous route, the administration devices were also analyzed.Prelicensing data of EPARs (six different biosimilar adalimumabs, three infliximabs, three etanercepts, three rituximabs, two bevacizumabs, and six trastuzumabs) revealed that the frequency of fatal treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation of treatment, serious adverse events (SAEs), and main immune-mediated adverse events (AEs) were comparable between the biosimilars and their reference products. The availability of new biosimilar presentations and administration devices may add to patient choice and be an emerging factor in the decision to switch patients. Analysis of postmarketing surveillance data covering up to 7 years of follow-up did not reveal any biosimilar-specific adverse effects. No product was withdrawn for safety reasons. This is in spite of considerable exposure to biosimilars in treatment-naïve patients and in patients switched from the reference medicinal product to the biosimilar. Analysis of data from switching studies provided in regulatory submissions showed that single or multiple switches between the originator and its biosimilar versions had no negative impact on efficacy, safety or immunogenicity.In line with previous reports of prelicensing studies of biosimilar mAbs and etanercepts, this study demonstrated comparable efficacy, safety, and immunogenicity compared with the reference products. This is the first study to comprehensively analyze postmarketing surveillance data of the biosimilar mAbs and etanercept. An analysis of more than 1 million patient-treatment years of safety data raised no safety concerns. Based on these data, we argue that biosimilars approved in the EU are highly similar to and interchangeable with their reference products. Thus, additional systematic switch studies are not required to support the switching of patients.
Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study
Authors: Andrew Menzies-Gow, Mark Gurnell, Liam G Heaney, Jonathan Corren, Elisabeth H Bel, Jorge Maspero, Timothy Harrison, David J Jackson, David Price, Njira Lugogo, James Kreindler, Annie Burden, Alex de Giorgio-Miller, Kelly Padilla, Ubaldo J Martin, Esther Garcia Gil
Journal: The Lancet Respiratory Medicine (2021)
Network propagation-based prioritization of long tail genes in 17 cancer types
Authors: Hussein Mohsen, Vignesh Gunasekharan, Tao Qing, Montrell Seay, Yulia Surovtseva, Sahand Negahban, Zoltan Szallasi, Lajos Pusztai, Mark B. Gerstein
Journal: Genome biology (2021)

The diversity of genomic alterations in cancer poses challenges to fully understanding the etiologies of the disease. Recent interest in infrequent mutations, in genes that reside in the "long tail" of the mutational distribution, uncovered new genes with significant implications in cancer development. The study of cancer-relevant genes often requires integrative approaches pooling together multiple types of biological data. Network propagation methods demonstrate high efficacy in achieving this integration. Yet, the majority of these methods focus their assessment on detecting known cancer genes or identifying altered subnetworks. In this paper, we introduce a network propagation approach that entirely focuses on prioritizing long tail genes with potential functional impact on cancer development.
1446P Weekly hypofractionated palliative radiotherapy in poor performance status and elderly patients unfit for standard radiotherapy: Survival, acute and late toxicity outcomes
Authors: C.P. Soatti, F. Colangelo, G. Mandurino, R. D'Amico, A. Alghisi, G. De Nobili, A. Cocchi, G. Sangalli, C. Frigerio, I. Butti, F. Bonsignore, F. Declich, D. Delishaj
Journal: Annals of Oncology (2021)
Right atrial mass diagnosed during endoscopic ultrasound in a patient with intraductal papillary mucinous neoplasm of the pancreas and dyspnea
Authors: Silvia Carrara, Marco Spadaccini, Matteo Colombo, Vittorio Pedicini, Lucia Torracca, Alessandro Repici
Journal: Endoscopy (2021)

A 70-year-old woman with a 10-year history of a 30-mm pancreatic cyst was referred to our center to continue follow-up. Of note, before the procedure she reported worsening dyspnea and fatigue over the last 4 months. However, no significant alterations were found on either preliminary cardiological or pneumological evaluation. Endoscopic ultrasound (EUS) confirmed the multilocular cystic lesion in the pancreatic body originating from the branch ducts, with focally thickened enhanced walls and a dilation of the main pancreatic duct (6 mm), as per a mixed-type intraductal papillary mucinous neoplasm (IPMN) with worrisome features. While withdrawing the echoendoscope into the mediastinum, a mainly hyperechoic 70 × 50-mm inhomogeneous mass was detected in the right atrium ([Video 1]), with an extension towards the superior vena cava access ([Fig. 1]). Owing to the suspicion of a cardiac mass, multimodality cardiac imaging was performed, confirming an endoluminal right atrial mass ([Fig. 2]), with inhomogeneous contrast enhancement, partially engaging the atrial outlet of the superior vena cava ([Fig. 3]). Thus, the patient underwent surgical resection of the mass.
1561O The future of the oncology workforce since COVID-19: Results of the ESMO Resilience Task Force survey series
Authors: K.H.J. Lim, K. Punie, C. Oing, E. Thorne, K. Murali, K.V. Kamposioras, M. O'Connor, E. Elez, T.M.S. Amaral, P. Garrido Lopez, M. Lambertini, B. Devnani, C.B. Westphalen, G. Morgan, J.B.A.G. Haanen, C. Hardy, S. Banerjee
Journal: Annals of Oncology (2021)
634P Prognostic value of the modeled PSA kinetic parameter (KELIM) in prostate cancer patients with rising PSA after primary local therapy treated in a prospective phase III trial with ADT +/- docetaxel
Authors: A. Carrot, R-T. Elaidi, O. Colomban, D. Maillet, M. Tod, B. You, S. Oudard
Journal: Annals of Oncology (2021)
1370TiP Befotertinib versus icotinib as first-line treatment in patients with advanced or metastatic EGFR-mutated non-small cell lung cancer: A multicenter, randomized, open-label, controlled phase III study
Authors: S. Lu, J. Zhou, H. Jian, L. Wu, Y. Cheng, Y. Fan, J. Fang, G. Chen, Z. Zhang, D. Lv, L. Jiang, R. Wu, X. Jin, X. Zhang, J. Zhang, G. Sun, D. Huang, J. Cui, R. Guo, L. Ding
Journal: Annals of Oncology (2021)
LBA18 POSEIDON randomized phase II trial: Tamoxifen (TAM) + taselisib or placebo (PLA) in patients (pts) with hormone receptor positive (HR+)/HER2- metastatic breast cancer (MBC)
Authors: M. Oliveira, R.D. Baird, R.A.B. Voorthuis, L. De Boo, A.G.J. van Rossum, L. Garrigos Cubells, S. Muñoz, D. López-García, C. Saura Manich, M. Schrier, I. Mandjes, K. Sikorska, M. Schot, A. Kateb, C. Mather, K. Beelen, J. Cortés, C. Caldas, S.C. Linn
Journal: Annals of Oncology (2021)
Skin of color representation in medical education: An analysis of National Board of Medical Examiners' self-assessments and popular question banks
Authors: Abigail L. Meckley, Colby L. Presley, Mindy D. Szeto, Cassandra Johnson, Victoria McCarver, Ezra Hoover, Sameeha S. Husayn, Taylor Harp, Taylor M. Runion, Michelle Militello, Robert P. Dellavalle
Journal: Journal of the American Academy of Dermatology (2021)