tbuckley/cabot-search huggingface dataset:
Fully Integrated Quantitative Multiparametric Analysis of Non–Small Cell Lung Cancer at 3-T PET/MRI
Authors: Florent L. Besson, Brice Fernandez, Sylvain Faure, Olaf Mercier, Andrei Seferian, Sacha Mussot, Antonin Levy, Florence Parent, Sophie Bulifon, Xavier Jais, David Montani, Delphine Mitilian, Elie Fadel, David Planchard, Maria-Rosa Ghigna-Bellinzoni, Claude Comtat, Vincent Lebon, Emmanuel Durand
Journal: Clinical Nuclear Medicine (2021)

The aim of this study was to study the feasibility of a fully integrated multiparametric imaging framework to characterize non-small cell lung cancer (NSCLC) at 3-T PET/MRI.An 18F-FDG PET/MRI multiparametric imaging framework was developed and prospectively applied to 11 biopsy-proven NSCLC patients. For each tumor, 12 parametric maps were generated, including PET full kinetic modeling, apparent diffusion coefficient, T1/T2 relaxation times, and DCE full kinetic modeling. Gaussian mixture model-based clustering was applied at the whole data set level to define supervoxels of similar multidimensional PET/MRI behaviors. Taking the multidimensional voxel behaviors as input and the supervoxel class as output, machine learning procedure was finally trained and validated voxelwise to reveal the dominant PET/MRI characteristics of these supervoxels at the whole data set and individual tumor levels.The Gaussian mixture model-based clustering clustering applied at the whole data set level (17,316 voxels) found 3 main multidimensional behaviors underpinned by the 12 PET/MRI quantitative parameters. Four dominant PET/MRI parameters of clinical relevance (PET: k2, k3 and DCE: ve, vp) predicted the overall supervoxel behavior with 97% of accuracy (SD, 0.7; 10-fold cross-validation). At the individual tumor level, these dimensionality-reduced supervoxel maps showed mean discrepancy of 16.7% compared with the original ones.One-stop-shop PET/MRI multiparametric quantitative analysis of NSCLC is clinically feasible. Both PET and MRI parameters are useful to characterize the behavior of tumors at the supervoxel level. In the era of precision medicine, the full capabilities of PET/MRI would give further insight of the characterization of NSCLC behavior, opening new avenues toward image-based personalized medicine in this field.
The Correlation Studies between Central Nervous System Involvement By Flow Cytometry and the Prognosis of Children Acute Lymphoblastic Leukemia: A Single Chinese Center's Experience By Cclg- ALL 2008
Authors: Wenyu Yang, Ye Guo, Xiaojuan Chen, Li Zhang, Yao Zou, Yumei Chen, Xiaofan Zhu
Journal: Blood (2017)
RECOGNIZING, DIAGNOSING, AND TREATING TRANSTHYRETIN AMYLOID CARDIOMYOPATHY (ATTR-CM): TARGETING CONTINUING MEDICAL EDUCATION (CME) TO THOSE WHO AREN’T TREATING ATTR-CM
Authors: Yvette M. Murley, Steve Bender, Marlene O. Heeg, Jonathan S. Simmons, Denise C. LaTemple, Grace Lin
Journal: Journal of the American College of Cardiology (2021)
IMMOBILE LEAFLETS AT THE TIME OF BIOPROSTHETIC VALVE IMPLANTATION: UNDER-RECOGNIZED BUT CLINICALLY IMPORTANT
Authors: Jwan Naser, Sorin Pislaru, Vuyisile Nkomo, Jeffrey Geske, Jeremy Thaden, Sushil Luis, Juan Crestanello, Jason Anderson, Hector Michelena, Ratnasari Padang
Journal: Journal of the American College of Cardiology (2021)
CARDIAC DYSFUNCTION IN WOMEN WITH HISTORY OF HYPERTENSIVE DISORDERS OF PREGNANCY: RESULTS FROM THE HISPANIC COMMUNITY HEALTH STUDY / STUDY OF LATINOS (HCHS/SOL)
Authors: Odayme Quesada, Min Wu, Natalie Bello, Alvin Chandra, Nour Makarem, Carlos Rodriguez, Catherine J. Vladutiu, Gregory Talavera, Timothy Henry, C. Noel Bairey Merz, Scott Solomon, Susan Cheng
Journal: Journal of the American College of Cardiology (2021)
ASSOCIATION OF HEALTH INSURANCE PAYER SOURCE AND OUTCOMES AFTER DURABLE LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION - AN ANALYSIS OF THE STS-INTERMACS REGISTRY
Authors: Sameed Ahmed Khatana, Thomas Hanff, Ashwin Nathan, Elias Dayoub, Edward Grandin, Jesus Rame, Alexander Fanaroff, Jay Giri, Peter Groeneveld
Journal: Journal of the American College of Cardiology (2021)
USE OF CT CORONARY ANGIOGRAPHY AS A DIAGNOSTIC MODALITY AND PLATELET-PHERESIS AS TREATMENT IN PATIENT WITH ESSENTIAL THROMBOCYTHEMIA PRESENTING WITH A NON ST ELEVATION MYOCARDIAL INFARCTION
Authors: Adnan Yousaf, Akram Alkrekshi, Muhammad U. Ali, Ahmad Jabri, Zahra Khaled, Aisha Siraj
Journal: Journal of the American College of Cardiology (2021)
IMPACT OF PACEMAKER IMPLANT ≤ 30 DAYS POST TAVR ON MORTALITY: RESULTS OF A SINGLE CENTER PROSPECTIVE REGISTRY
Authors: Claudia See, Yanting Wang, Yiping Yang, Daniela Tirziu, Nikolaos Papoutsidakis, Ryan Kaple, Michael Cleman, Alexandra Lansky, John Forrest
Journal: Journal of the American College of Cardiology (2021)
Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3
Authors: Qianying Yuan, Abdul Basit, Wenhua Liang, Rihao Qu, Yi Luan, Chunguang Ren, Ao Li, Xin Xu, Xiaoqing Liu, Chun Yang, Andrew Kuo, Richard Pierce, Longbo Zhang, Benjamin Turk, Xin Hu, Fangyong Li, Weixue Cui, Run Li, Danxia Huang, Lili Mo, William C. Sessa, Patty J. Lee, Yuval Kluger, Bing Su, Wenwen Tang, Jianxing He, Dianqing Wu
Journal: Science Translational Medicine (2021)

MAP3K inhibition attenuates acute lung injuries in mice and reduced edema in lung transplantation recipients.
THE DIFFERENCE IN THE IMPACT OF SOCIOECONOMIC STATUS ON SURGICAL VS TRANSCATHETER MITRAL VALVE REPAIR
Authors: Alexis K. Okoh, Fady Soliman, Xiaoyan Deng, Sameer Hirji, Paige Newell, Setri Fugar, John Kassotis, Abdul Hakeem, Leonard Lee, Chunguang Chen, Tsuyoshi Kaneko, Mark Russo
Journal: Journal of the American College of Cardiology (2021)
A nano-predator of pathological MDMX construct by clearable supramolecular gold(I)-thiol-peptide complexes achieves safe and potent anti-tumor activity
Authors: Siqi Yan, Jin Yan, Dan Liu, Xiang Li, Qianyan Kang, Weiming You, Jinghua Zhang, Lei Wang, Zhiqi Tian, Wuyuan Lu, Wenjia Liu, Wangxiao He
Journal: Theranostics (2021)

As alternatives to small-molecular proteolysis-targeting chimeras (PROTAC), peptide-based molecular glues (MG) are a broad range of dual-functional ligands that simultaneously bind with targetable proteins and E3 ligases by mimicking proteinprotein interaction (PPI) partners. Methods: Herein, we design a peptide-derived MG to target a tumor-driving protein, MDMX, for degradation, and nanoengineered it into a supramolecular gold(I)-thiol-peptide complex (Nano-MP) to implement the proteolysis recalcitrance, cellular internalization, and glutathione-triggered release. To optimize the tumor targeting, a pH-responsive macromolecule termed polyacryl sulfydryl imidazole (PSI) was synthesized to coat Nano-MP. Results: As expected, Nano-MP@PSI induced the MDMX degradation by ubiquitination and subsequently restored the anti-cancer function of p53 and p73. Nano-MP@PSI revealed potent anti-cancer activities in an orthotopic xenograft mouse model of retinoblastoma by intraocular injection and a patient-derived xenograft model of malignant pancreatic cancer by systemic injection, while maintaining a favorable safety profile and showing a highly favorable clearable profile of excretion from the living body. Conclusion: Collectively, this work not only provided a clinically viable paradigm for the treatment of a wide variety of tumors by multiple administration types, but, more importantly, it bridged the chasm between peptides and PROTACs, and likely reinvigorated the development of peptide-derived proteolysis-targeting chimeras for a great variety of diseases.
Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study
Authors: Cristina Menni, Kerstin Klaser, Anna May, Lorenzo Polidori, Joan Capdevila, Panayiotis Louca, Carole H Sudre, Long H Nguyen, David A Drew, Jordi Merino, Christina Hu, Somesh Selvachandran, Michela Antonelli, Benjamin Murray, Liane S Canas, Erika Molteni, Mark S Graham, Marc Modat, Amit D Joshi, Massimo Mangino, Alexander Hammers, Anna L Goodman, Andrew T Chan, Jonathan Wolf, Claire J Steves, Ana M Valdes, Sebastien Ourselin, Tim D Spector
Journal: The Lancet Infectious Diseases (2021)
Electrophoretic deposition of silk fibroin coatings with pre-defined architecture to facilitate precise control over drug delivery
Authors: Xian Cheng, Dingpei Long, Lili Chen, John A. Jansen, Sander C.G. Leeuwenburgh, Fang Yang
Journal: Bioactive Materials (2021)

The therapeutic precision and clinical applicability of drug-eluting coatings can be substantially improved by facilitating tunable drug delivery. However, the design of coatings which allows for precise control over drug release kinetics is still a major challenge. Here, a double-layered silk fibroin (SF) coating system was constructed by sequential electrophoretic deposition. A mixture of dissolved Bombyx mori SF (bmSF) molecules and pre-made bmSF nanospheres at different ratios was deposited as under-layer. Subsequently, this underlayer was covered by a top-layer comprising Antheraea pernyi SF (apSF) molecules (rich in arginylglycylaspartic acid, RGD) to improve the cellular response of the resulting double-layered coatings. Additionally, model drug doxycycline was either pre-mixed with dissolved bmSF molecules or pre-loaded into pre-made bmSF nanospheres at the same amount before their mixing and deposition. The thickness and nanosphere content of the under-layer architecture were proportional to the deposition time and nanosphere concentration in precursor mixtures, respectively. The surface topography, wettability, degradation rate and adhesion strength were comparable within the double-layered coating system. As expected, RGD-rich apSF top-layer improved cell adhesion, spreading and proliferation compared with bmSF top-layer. Furthermore, the amount and duration of drug release increased linearly with increasing nanosphere concentration at fixed deposition time, whereas drug release amount increased linearly with increasing deposition time. These results indicate that the dosage and kinetics of loaded drugs can be quantitatively tailored by altering nanosphere concentration and deposition time as main processing parameters. Overall, this study illustrates the strong potential of pre-defining coating architecture to facilitate control over drug delivery.
THE EFFECT OF NSAID USE ON POSTPARTUM HYPERTENSION: A SYSTEMIC REVIEW AND META-ANALYSIS
Authors: Jeremy C. Tomcho, Mitra Patel, Ahmed Elzanaty, Sapan Bhuta, Neha Patel, Omar Sajdeya, Mohammed Mhanna, Pinang Shastri, Cameron Burmeister, Azizullah Beran, Sami Ghazaleh
Journal: Journal of the American College of Cardiology (2021)
Variant Intronic Enhancer Controls <i>SCN10A-short</i> Expression and Heart Conduction
Authors: Joyce C.K. Man, Fernanda M. Bosada, Koen T. Scholman, Joost A. Offerhaus, Roddy Walsh, Karel van Duijvenboden, Vincent W.W. van Eif, Connie R. Bezzina, Arie O. Verkerk, Bastiaan J. Boukens, Phil Barnett, Vincent M. Christoffels
Journal: Circulation (2021)

Genetic variants in SCN10A, encoding the neuronal voltage-gated sodium channel NaV1.8, are strongly associated with atrial fibrillation, Brugada syndrome, cardiac conduction velocities, and heart rate. The cardiac function of SCN10A has not been resolved, however, and diverging mechanisms have been proposed. Here, we investigated the cardiac expression of SCN10A and the function of a variant-sensitive intronic enhancer previously linked to the regulation of SCN5A, encoding the major essential cardiac sodium channel NaV1.5.The expression of SCN10A was investigated in mouse and human hearts. With the use of CRISPR/Cas9 genome editing, the mouse intronic enhancer was disrupted, and mutant mice were characterized by transcriptomic and electrophysiological analyses. The association of genetic variants at SCN5A-SCN10A enhancer regions and gene expression were evaluated by genome-wide association studies single-nucleotide polymorphism mapping and expression quantitative trait loci analysis.We found that cardiomyocytes of the atria, sinoatrial node, and ventricular conduction system express a short transcript comprising the last 7 exons of the gene (Scn10a-short). Transcription occurs from an intronic enhancer-promoter complex, whereas full-length Scn10a transcript was undetectable in the human and mouse heart. Expression quantitative trait loci analysis revealed that the genetic variants in linkage disequilibrium with genetic variant rs6801957 in the intronic enhancer associate with SCN10A transcript levels in the heart. Genetic modification of the enhancer in the mouse genome led to reduced cardiac Scn10a-short expression in atria and ventricles, reduced cardiac sodium current in atrial cardiomyocytes, atrial conduction slowing and arrhythmia, whereas the expression of Scn5a, the presumed enhancer target gene, remained unaffected. In patch-clamp transfection experiments, expression of Scn10a-short-encoded NaV1.8-short increased NaV1.5-mediated sodium current. We propose that noncoding genetic variation modulates transcriptional regulation of Scn10a-short in cardiomyocytes that impacts NaV1.5-mediated sodium current and heart rhythm.Genetic variants in and around SCN10A modulate enhancer function and expression of a cardiac-specific SCN10A-short transcript. We propose that noncoding genetic variation modulates transcriptional regulation of a functional C-terminal portion of NaV1.8 in cardiomyocytes that impacts on NaV1.5 function, cardiac conduction velocities, and arrhythmia susceptibility.
IMPACT OF INTRAPLAQUE HEMORRHAGE, CHOLESTEROL CRYSTALS AND HEALED PLAQUES ON LONG-TERM OUTCOME IN NON-CULPRIT LESIONS ASSESSED BY OPTICAL COHERENCE TOMOGRAPHY
Authors: Eisuke Usui, Mitsuaki Matsumura, Fumiyasu Seike, Allen Jeremias, Evan Shlofmitz, Ziad Ali, James Nguyen, Craig Porter, Jie Cao, Thomas Pappas, George Petrossian, Jeffrey Moses, Gary Mintz, Richard Shlofmitz, Akiko Maehara
Journal: Journal of the American College of Cardiology (2021)
Abstract 19112: Retardation of Progression of Mild Aortic Stenosis (AS) by Angiotensin or Aldosterone Antagonism
Authors: Oral Waldo, Pragnesh P Parikh, Joseph Blackshear
Journal: Circulation (2013)

Aortic stenosis is the most common acquired valvular heart disease. Currently, there are no medications approved to slow its progression. We set out to investigate the effect of ACE inhibitors/angiotensin receptor blockers and aldosterone antagonists on the rate of progression of mild aortic stenosis. We retrospectively reviewed the charts of 2,613 patients over 45 years old, who had a peak velocity between 1.8 and 3 meters/second on initial echo. Over 8 years of followup, 491 patients were prescribed angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) and 130 patients were prescribed aldosterone receptor blockers. Patients prescribed ACE inhibitors/ARBs had a slower rate of progression of aortic stenosis compared to those not prescribed ACE inhibitors/ARBs (2.2 to 2.5 vs. 2.3 to 2.8 meters/second) (Figure 1). Also, patients prescribed aldosterone receptor blockers had a slower rate of progression of aortic stenosis compared to those who were not 2.2 to 2.4 vs. 2.3 to 2.8 meters/second) (Figure 2). Our findings suggest that angiotensin or aldosterone antagonism is associated with slower rate of progression of mild aortic stenosis.
Long-term outcomes of patients following hospitalization for coronavirus disease 2019: a prospective observational study
Authors: Yolanda Meije, Alejandra Duarte-Borges, Xavier Sanz, Mercedes Clemente, Alba Ribera, Lucía Ortega, Ruth González-Pérez, Roser Cid, Júlia Pareja, Irene Cantero, Miquel Ariño, Teresa Sagués, Jaume LLaberia, Ana Ayestarán, Nuria Fernández-Hidalgo, Beatriz Candás-Estébanez, N. Alguersuari, A. Arderiu, N. Baeza, J. Bugés, J. Cabello, M. Campillo, J. Cantos, E. Castellarnau, A. Coco, I. Coll, D. Coroleu, J. Costa, X. Demestre, P. Díez-Cascón, M.J. Elizari, I. Escape, N. Espaulella, J. Fabregat, C. Ferré, M. Ferrer, F. Franco, J. Galí, E. García, J. Garrillo, C. Guzmán, L. Iglesias, L. Invernón, J. Jimeno, J. Lima, M. León, G. Martí, S. Martínez, J. Martínez-Agea, L. Martínez-Fijo, J. Martínez-Montauti, A. Martínez-Trillos, S. Mechó, A. Méndez, B. Mendiola, J. Mercé, F. Miranda, J. Morillas, M. Montané, A. Musolas, A. Odriozola, V. Pagès, J. Palau, M.A. Palos, E. Parra, J.R. Pérez-Mas, K. Pizurno, M. Ponce, S. Pons, D. Redó, N. Rodón, G. Rodríguez-Froxán, A. Santamaría, C. Sitges, N. Stasi, J.M. Soler, A. Torrens, M. Vaqué, L. Ventura, C. Vericat, A. Vila
Journal: Clinical Microbiology and Infection (2021)
Impact of the revised definition of extensively drug-resistant tuberculosis
Authors: Nicolas Veziris, Isabelle Bonnet, Florence Morel, Lorenzo Guglielmetti, Thomas Maitre, Laure Fournier Le Ray, Wladimir Sougakoff, Jérôme Robert, Alexandra Aubry
Journal: European Respiratory Journal (2021)

Recently, the World Health Organization (WHO) has released a revised definition of extensively drug-resistant (XDR) tuberculosis (TB) that should be used for clinical and surveillance purposes starting from 1 January, 2021 [1, 2]. The previous definition of XDR-TB was TB that is resistant to any fluoroquinolone (levofloxacin and/or moxifloxacin) and to at least one of three second-line injectable drugs (SLIs: capreomycin, kanamycin and amikacin), in addition to multidrug resistance. The revised definition is: TB caused by Mycobacterium tuberculosis strains that fulfil the definition of MDR/RR-TB and which are also resistant to any fluoroquinolone and at least one additional group A drug. WHO group A drugs currently include fluoroquinolones (levofloxacin or moxifloxacin), linezolid and bedaquiline. In addition, pre-XDR-TB is now a WHO-endorsed definition, identified as MDR/RR-TB with any fluoroquinolone resistance. Although the previous definition of XDR-TB has proved to be predictive of poor treatment outcome [3], the 2020 update appears in line with recent changes of treatment regimens given, i.e. less frequent use of SLI in favour of the potent oral drugs, bedaquiline and linezolid. Moreover, a large meta-analysis failed to show an association between mortality reduction and SLI use, whereas this association was shown for bedaquiline and linezolid [4]. In this study, we aimed to measure retrospectively the impact of the revised definition on the epidemiology of XDR-TB in France. The revised WHO definition of XDR-TB decreases the number of TB cases classified as such, and allows better focus on the most difficult to treat cases of TB <https://bit.ly/3tgaXQA> We thank all technicians working at the CNR-MyRMA for their dedication to their work.
Functional and genetic determinants of mutation rate variability in regulatory elements of cancer genomes
Authors: Christian A. Lee, Diala Abd-Rabbo, Jüri Reimand
Journal: Genome biology (2021)

Abstract Background Cancer genomes are shaped by mutational processes with complex spatial variation at multiple scales. Entire classes of regulatory elements are affected by local variations in mutation frequency. However, the underlying mechanisms with functional and genetic determinants remain poorly understood. Results We characterise the mutational landscape of 1.3 million gene-regulatory and chromatin architectural elements in 2419 whole cancer genomes with transcriptional and pathway activity, functional conservation and recurrent driver events. We develop RM2, a statistical model that quantifies mutational enrichment or depletion in classes of genomic elements through genetic, trinucleotide and megabase-scale effects. We report a map of localised mutational processes affecting CTCF binding sites, transcription start sites (TSS) and tissue-specific open-chromatin regions. Increased mutation frequency in TSSs associates with mRNA abundance in most cancer types, while open-chromatin regions are generally enriched in mutations. We identify ~ 10,000 CTCF binding sites with core DNA motifs and constitutive binding in 66 cell types that represent focal points of mutagenesis. We detect site-specific mutational signature enrichments, such as SBS40 in open-chromatin regions in prostate cancer and SBS17b in CTCF binding sites in gastrointestinal cancers. Candidate drivers of localised mutagenesis are also apparent: BRAF mutations associate with mutational enrichments at CTCF binding sites in melanoma, and ARID1A mutations with TSS-specific mutagenesis in pancreatic cancer. Conclusions Our method and catalogue of localised mutational processes provide novel perspectives to cancer genome evolution, mutagenesis, DNA repair and driver gene discovery. The functional and genetic correlates of mutational processes suggest mechanistic hypotheses for future studies.
No end in sight for the Brazilian COVID-19 crisis
Authors: Talha Burki
Journal: The Lancet Microbe (2021)

As The Lancet Microbe went to press, the number of Brazilians to have died from COVID-19 had passed 350 000. Only the USA has a higher death toll. The pandemic has brought Brazil's health-care system to the verge of collapse. By the end of March, 2021, intensive care units in 17 of the country's 27 states were at more than 90% occupancy (seven others were at more than 80% occupancy). Supplies of drugs and oxygen are running short. On April 15, Médecins Sans Frontières warned of a "humanitarian catastrophe" in Brazil.
Cervical screening during the COVID-19 pandemic: optimising recovery strategies
Authors: Alejandra Castanon, Matejka Rebolj, Emily Annika Burger, Inge M C M de Kok, Megan A Smith, Sharon J B Hanley, Francesca Maria Carozzi, Stuart Peacock, James F O'Mahony
Journal: The Lancet Public Health (2021)

Disruptions to cancer screening services have been experienced in most settings as a consequence of the COVID-19 pandemic. Ideally, programmes would resolve backlogs by temporarily expanding capacity; however, in practice, this is often not possible. We aim to inform the deliberations of decision makers in high-income settings regarding their cervical cancer screening policy response. We caution against performance measures that rely solely on restoring testing volumes to pre-pandemic levels because they will be less effective at mitigating excess cancer diagnoses than will targeted measures. These measures might exacerbate pre-existing inequalities in accessing cervical screening by disregarding the risk profile of the individuals attending. Modelling of cervical screening outcomes before and during the pandemic supports risk-based strategies as the most effective way for screening services to recover. The degree to which screening is organised will determine the feasibility of deploying some risk-based strategies, but implementation of age-based risk stratification should be universally feasible.