tbuckley/cabot-search huggingface dataset:
Lancet COVID-19 Commission Statement on the occasion of the 75th session of the UN General Assembly
Authors: Jeffrey D Sachs, Salim Abdool Karim, Lara Aknin, Joseph Allen, Kirsten Brosbøl, Gabriela Cuevas Barron, Peter Daszak, María Fernanda Espinosa, Vitor Gaspar, Alejandro Gaviria, Andy Haines, Peter Hotez, Phoebe Koundouri, Felipe Larraín Bascuñán, Jong-Koo Lee, Muhammad Pate, Paul Polman, Srinath Reddy, Ismail Serageldin, Raj Shah, John Thwaites, Vaira Vike-Freiberga, Chen Wang, Miriam Khamadi Were, Lan Xue, Min Zhu, Chandrika Bahadur, Maria Elena Bottazzi, Yanis Ben Amor, Lauren Barredo, Ozge Karadag Caman, Guillaume Lafortune, Emma Torres, Ismini Ethridge, Juliana G E Bartels
Journal: The Lancet (2020)

The Lancet COVID-19 Commission was launched on July 9, 2020, to assist governments, civil society, and UN institutions in responding effectively to the COVID-19 pandemic. The Commission aims to offer practical solutions to the four main global challenges posed by the pandemic: suppressing the pandemic by means of pharmaceutical and non-pharmaceutical interventions; overcoming humanitarian emergencies, including poverty, hunger, and mental distress, caused by the pandemic; restructuring public and private finances in the wake of the pandemic; and rebuilding the world economy in an inclusive, resilient, and sustainable way that is aligned with the Sustainable Development Goals (SDGs) and the Paris Climate Agreement.
Pembrolizumab Exacerbates Thyroid Diseases Shown on FDG PET/CT
Authors: Xuezhu Wang, Jingnan Wang, Xu Yang, Haitao Zhao, Li Huo
Journal: Clinical Nuclear Medicine (2020)

Abstract A 51-year-old woman with a history of sarcomatoid hepatocellular carcinoma, status post resection, underwent FDG PET/CT. In addition to abnormal activity elsewhere, the images showed focal activity in the isthmus of the thyroid, suggestive of malignant involvement, and diffuse mild activity in the left lobe of the thyroid, suggestive of thyroiditis. After a 10-week anti–PD-1 pembrolizumab therapy, the follow-up FDG PET/CT scan demonstrated much more intense activity in both the isthmus and the left lobe of the thyroid. Pathological examination revealed papillary thyroid cancer in the isthmus and thyroiditis in the left lobe of the thyroid.
Ultrasensitive deletion detection links mitochondrial DNA replication, disease, and aging
Authors: Scott A. Lujan, Matthew J. Longley, Margaret H. Humble, Christopher A. Lavender, Adam Burkholder, Emma L. Blakely, Charlotte L. Alston, Grainne S. Gorman, Doug M. Turnbull, Robert McFarland, Robert W. Taylor, Thomas A. Kunkel, William C. Copeland
Journal: Genome biology (2020)

Abstract Background Acquired human mitochondrial genome (mtDNA) deletions are symptoms and drivers of focal mitochondrial respiratory deficiency, a pathological hallmark of aging and late-onset mitochondrial disease. Results To decipher connections between these processes, we create LostArc, an ultrasensitive method for quantifying deletions in circular mtDNA molecules. LostArc reveals 35 million deletions (~ 470,000 unique spans) in skeletal muscle from 22 individuals with and 19 individuals without pathogenic variants in POLG. This nuclear gene encodes the catalytic subunit of replicative mitochondrial DNA polymerase γ. Ablation, the deleted mtDNA fraction, suffices to explain skeletal muscle phenotypes of aging and POLG-derived disease. Unsupervised bioinformatic analyses reveal distinct age- and disease-correlated deletion patterns. Conclusions These patterns implicate replication by DNA polymerase γ as the deletion driver and suggest little purifying selection against mtDNA deletions by mitophagy in postmitotic muscle fibers. Observed deletion patterns are best modeled as mtDNA deletions initiated by replication fork stalling during strand displacement mtDNA synthesis.
COVID-19–related Respiratory Failure and Lymphopenia Do Not Seem Associated with Pneumocystosis
Authors: Marion Blaize, Julien Mayaux, Charles-Edouard Luyt, Alexandre Lampros, Arnaud Fekkar
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Primary Prevention Trial Designs Using Coronary Imaging
Authors: Philip Greenland, Erin D. Michos, Nicole Redmond, Lawrence J. Fine, Karen P. Alexander, Walter T. Ambrosius, Kirsten Bibbins-Domingo, Michael J. Blaha, Ron Blankstein, Stephen P. Fortmann, Amit Khera, Donald M. Lloyd-Jones, David J. Maron, James K. Min, J. Brent Muhlestein, Khurram Nasir, Madeline R. Sterling, George Thanassoulis
Journal: JACC. Cardiovascular imaging (2020)
Cardiac Disease in Childhood Cancer Survivors
Authors: Jan M. Leerink, Esmée C. de Baat, Elizabeth A.M. Feijen, Louise Bellersen, Elvira C. van Dalen, Heynric B. Grotenhuis, Livia Kapusta, Wouter E.M. Kok, Jacqueline Loonen, Heleen J.H. van der Pal, Saskia M.F. Pluijm, Arco J. Teske, Annelies M.C. Mavinkurve-Groothuis, Remy Merkx, Leontien C.M. Kremer
Journal: JACC CardioOncology (2020)

Cardiac diseases in the growing population of childhood cancer survivors are of major concern. Cardiotoxicity as a consequence of anthracyclines and chest radiotherapy continues to be relevant in the modern treatment era. Mitoxantrone has emerged as an important treatment-related risk factor and evidence on traditional cardiovascular risk factors in childhood cancer survivors is accumulating. International surveillance guidelines have been developed with the aim to detect and manage cardiac diseases early and prevent symptomatic disease. There is growing interest in risk prediction models to individualize prevention and surveillance. This State-of-the-Art Review summarizes literature from a systematic PubMed search focused on cardiac diseases after treatment for childhood cancer. Here, we discuss the prevalence, risk factors, prevention, risk prediction, and surveillance of cardiac diseases in survivors of childhood cancer.
Final Overall Survival Results from a Phase 3 Study to Compare Tivozanib to Sorafenib as Third- or Fourth-line Therapy in Subjects with Metastatic Renal Cell Carcinoma
Authors: Sumanta K. Pal, Bernard J. Escudier, Michael B. Atkins, Thomas E. Hutson, Camillo Porta, Elena Verzoni, Michael N. Needle, Daniel Powers, David F. McDermott, Brian I. Rini
Journal: European Urology (2020)
Biotin-decorated all-HPMA polymeric micelles for paclitaxel delivery
Authors: Yan Wang, Mies J. van Steenbergen, Nataliia Beztsinna, Yang Shi, Twan Lammers, Cornelus F. van Nostrum, Wim E. Hennink
Journal: Journal of Controlled Release (2020)

To avoid poly(ethylene glycol)-related issues of nanomedicines such as accelerated blood clearance, fully N-2-hydroxypropyl methacrylamide (HPMAm)-based polymeric micelles decorated with biotin for drug delivery were designed. To this end, a biotin-functionalized chain transfer agent (CTA), 4-cyano-4-[(dodecylsulfanylthiocarbonyl)-sulfanyl]pentanoic acid (biotin-CDTPA), was synthesized for reversible addition-fragmentation chain-transfer (RAFT) polymerization. Amphiphilic poly(N-2-hydroxypropyl methacrylamide)-block-poly(N-2-benzoyloxypropyl methacrylamide) (p(HPMAm)-b-p(HPMAm-Bz)) with molecular weights ranging from 8 to 24 kDa were synthesized using CDTPA or biotin-CDTPA as CTA and 2,2'-azobis(2-methylpropionitrile) as initiator. The copolymers self-assembled in aqueous media into micelles with sizes of 40-90 nm which positively correlated to the chain length of the hydrophobic block in the polymers, whereas the critical micelle concentrations decreased with increasing hydrophobic block length. The polymer with a molecular weight of 22.1 kDa was used to prepare paclitaxel-loaded micelles which had sizes between 61 and 70 nm, and a maximum loading capacity of around 10 wt%. A549 lung cancer cells overexpressing the biotin receptor, internalized the biotin-decorated micelles more efficiently than non-targeted micelles, while very low internalization of both types of micelles by HEK293 human embryonic kidney cells lacking the biotin receptor was observed. As a consequence, the paclitaxel-loaded micelles with biotin decoration exhibited stronger cytotoxicity in A549 cells than non-targeted micelles. Overall, a synthetic pathway to obtain actively targeted poly(ethylene glycol)-free micelles fully based on a poly(HPMAm) backbone was established. These polymeric micelles are promising systems for the delivery of hydrophobic anticancer drugs.
Therapy‐Induced Senescence Is a Predictor of Treatment Outcome in Acute Myeloid Leukemia
Authors: Martin Schönlein, J. Henry M. Däbritz, Dorothy Ngo-Yin Fan, Jana Ihlow, Rolf Schwarzer, Binje Vick, Karsten Spiekermann, Thomas Burmeister, Jörg Westermann, Irmela Jeremias, Clemens A. Schmitt
Journal: Blood (2017)
Frequency of Children vs Adults Carrying Severe Acute Respiratory Syndrome Coronavirus 2 Asymptomatically
Authors: Gregorio P. Milani, Ilaria Bottino, Alessia Rocchi, Paola Marchisio, Silvia Elli, Carlo Agostoni, Giorgio Costantino
Journal: JAMA Pediatrics (2020)

This case-control study compares the rates of test results indicating SARS-CoV-2 infection among children and adults admitted to a single hospital in Milan, Italy, for noninfectious reasons and without COVID-19 symptoms.
Cardio‐oncology care in the era of the coronavirus disease 2019 (COVID‐19) pandemic: An International Cardio‐Oncology Society (ICOS) statement
Authors: Daniel Lenihan, Joseph Carver, Charles Porter, Jennifer E. Liu, Susan Dent, Paaladinesh Thavendiranathan, Joshua D. Mitchell, Anju Nohria, Michael G. Fradley, Iskra Pusic, Keith Stockerl‐Goldstein, Anne Blaes, Alexander R. Lyon, Sarju Ganatra, Teresa López‐Fernández, Rupal O'Quinn, Giorgio Minotti, Sebastian Szmit, Daniela Cardinale, Jose Alvarez‐Cardona, Giuseppe Curigliano, Tomas G. Neilan, Joerg Herrmann
Journal: CA A Cancer Journal for Clinicians (2020)

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS–CoV‐2) has given rise to a pandemic of unprecedented proportions in the modern era because of its highly contagious nature and impact on human health and society: coronavirus disease 2019 (COVID‐19). Patients with cardiovascular (CV) risk factors and established CV disease (CVD) are among those initially identified at the highest risk for serious complications, including death. Subsequent studies have pointed out that patients with cancer are also at high risk for a critical disease course. Therefore, the most vulnerable patients are seemingly those with both cancer and CVD, and a careful, unified approach in the evaluation and management of this patient population is especially needed in times of the COVID‐19 pandemic. This review provides an overview of the unique implications of the viral outbreak for the field of cardio‐oncology and outlines key modifications in the approach to this ever‐increasing patient population. These modifications include a shift toward greater utilization of cardiac biomarkers and a more focused CV imaging approach in the broader context of modifications to typical practice pathways. The goal of this strategic adjustment is to minimize the risk of SARS–CoV‐2 infection (or other future viral outbreaks) while not becoming negligent of CVD and its important impact on the overall outcomes of patients who are being treated for cancer.
A Pesco-Mediterranean Diet With Intermittent Fasting
Authors: James H. O’Keefe, Noel Torres-Acosta, Evan L. O’Keefe, Ibrahim M. Saeed, Carl J. Lavie, Sarah E. Smith, Emilio Ros
Journal: Journal of the American College of Cardiology (2020)

As opportunistic omnivores, humans are evolutionarily adapted to obtain calories and nutrients from both plant and animal food sources. Today, many people overconsume animal products, often-processed meats high in saturated fats and chemical additives. Alternatively, strict veganism can cause nutritional deficiencies and predispose to osteopenia, sarcopenia, and anemia. A logical compromise is a plant-rich diet with fish/seafood as principal sources of animal food. This paper reviews cumulative evidence regarding diet and health, incorporating data from landmark clinical trials of the Mediterranean diet and recommendations from recent authoritative guidelines, to support the hypothesis that a Pesco-Mediterranean diet is ideal for optimizing cardiovascular health. The foundation of this diet is vegetables, fruits, nuts, seeds, legumes, whole grains, and extra-virgin olive oil with fish/seafood and fermented dairy products. Beverages of choice are water, coffee, and tea. Time-restricted eating is recommended, whereby intermittent fasting is done for 12 to 16 h each day.
Abstract 5851: Activation of Inflammatory and Apoptotic Pathways in Human Donor Heart Dysfunction
Authors: Christian F Bulcao, Karen M D’Souza, Ricky Malhotra, Michelle Staron, Prakash K Pandalai, Jody Y Duffy, Shahab A Akhter
Journal: Circulation (2008)

Donor heart dysfunction (DHD) precluding procurement for transplantation occurs in up to 25% of brain dead donors in the absence of structural heart disease. The molecular mechanisms of DHD remain unclear. We investigated the potential role of myocardial interleukin (IL)-6 signaling through the JAK2/STAT3 pathway which leads to the generation of nitric oxide (NO) and decreased cardiac myocyte contractility in vitro. NO can also lead to induction of the proapoptotic gene Bnip3 in vitro. Hearts were procured using standard technique with UW solution from 14 brain dead donors with a left ventricular ejection fraction of &lt; 30% (DHD) in the absence of structural heart disease. Six hearts with normal function (NF) that were procured but not transplanted for non-cardiac reasons served as controls. Left ventricular (LV) IL-6 levels were quantitated by ELISA and signaling through the JAK2/STAT3 pathway via IL-6 and gp130 receptors was assessed by expression of activated, or phosphorylated STAT3. NO signaling was measured by myocardial expression of inducible NO synthase (iNOS) and protein immunoblotting for Bnip3 was performed. Myocardial IL-6 protein levels were 8-fold greater in the DHD group vs. NF controls ( P &lt; 0.02). Phosphorylated STAT3 expression was 5-fold higher in DHD vs. NF ( P &lt; 0.01) indicating increased JAK2/STAT3 signaling as there was no difference in total STAT3 expression between groups ( P &gt;0.05). LV expression of iNOS was 2-fold greater in DHD vs. NF ( P &lt; 0.03) consistent with increased iNOS activity. In addition, LV expression of the proapoptotic gene Bnip3 was 3-fold greater in the DHD group vs. NF ( P &lt; 0.04) suggesting that apoptosis may contribute to DHD. N= 14 for DHD and n= 6 for NF in all studies. Increased myocardial IL-6-mediated signaling through the JAK2/STAT3 pathway leading to upregulation of iNOS and NO production may be an important mechanism in human DHD. Increased myocardial NO also appears to lead to upregulation of proapoptotic Bnip3 in cardiac myocytes, and apoptotic cell death may also contribute to ventricular dysfunction following brain death. Inhibition of IL-6/JAK2/STAT3 signaling may represent a novel strategy to increase the severely limited number of cardiac donors.
Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review
Authors: Claudio Sandroni, Sonia D’Arrigo, Sofia Cacciola, Cornelia W. E. Hoedemaekers, Marlijn J. A. Kamps, Mauro Oddo, Fabio S. Taccone, Arianna Di Rocco, Frederick J. A. Meijer, Erik Westhall, Massimo Antonelli, Jasmeet Soar, Jerry P. Nolan, Tobias Cronberg
Journal: Intensive Care Medicine (2020)

To assess the ability of clinical examination, blood biomarkers, electrophysiology, or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict poor neurological outcome, defined as death, vegetative state, or severe disability (CPC 3-5) at hospital discharge/1 month or later, in comatose adult survivors from cardiac arrest (CA).PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews (January 2013-April 2020) were searched. Sensitivity and false-positive rate (FPR) for each predictor were calculated. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed.Ninety-four studies (30,200 patients) were included. Bilaterally absent pupillary or corneal reflexes after day 4 from ROSC, high blood values of neuron-specific enolase from 24 h after ROSC, absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) or unequivocal seizures on electroencephalogram (EEG) from the day of ROSC, EEG background suppression or burst-suppression from 24 h after ROSC, diffuse cerebral oedema on brain CT from 2 h after ROSC, or reduced diffusion on brain MRI at 2-5 days after ROSC had 0% FPR for poor outcome in most studies. Risk of bias assessed using the QUIPS tool was high for all predictors.In comatose resuscitated patients, clinical, biochemical, neurophysiological, and radiological tests have a potential to predict poor neurological outcome with no false-positive predictions within the first week after CA. Guidelines should consider the methodological concerns and limited sensitivity for individual modalities. (PROSPERO CRD42019141169).
Leachable‐Free Fabrication of Hydrogel Foams Enabling Homogeneous Viability of Encapsulated Cells in Large‐Volume Constructs
Authors: Tânia Salvador, Mariana B. Oliveira, João F. Mano
Journal: Advanced Healthcare Materials (2020)

Abstract The popularity of cell‐laden injectable hydrogels has steeply increased due to their compatibility with minimally invasive surgical procedures. However, the diffusion of indispensable molecules for cell survival through bulk hydrogel structures, particularly oxygen, is often limited to micrometric distances, often hampering cell viability or uniform tissue formation in constructs with clinically relevant sizes. The introduction of micropores in hydrogels or the use of oxygen‐generating materials has enabled combining advantages of porous 3D scaffolds with the injectability properties of in situ‐solidifying hydrogels. Here, cell‐laden injectable gelatin methacryloyl (GelMA) foams are fabricated using a single polymer formulation. Air bubbles are introduced into GelMA solutions using a simple‐to‐implement method based on pulling/pushing the solution through a syringe. Human mesenchymal stem cells derived from the adipose tissue (hASCs) cultured in bulk hydrogels (diameter c.a. 5 mm) show low permanence in the core of the materials and stain for factors associated to hypoxia (hypoxia‐inducible factor‐1 alpha (HIF‐1 α )) after 7 days of culture. In opposition, cells cultured in optimized foams do not stain for HIF‐1 α , show high permanence, homogeneous viability, and consistent phenotype in the whole depth of the biomaterials, while secreting increased amounts of regenerative growth factors to the surrounding medium.
Incidental Detection of a Small Cell Lung Cancer by 18F-Choline PET/CT Performed for Recurrent Hyperparathyroidism After Parathyroidectomy
Authors: Nicolas Jacquet-Francillon, Denise Granjon, François Casteillo, Nathalie Prévot, Vincent Habouzit
Journal: Clinical Nuclear Medicine (2020)

Abstract We report the case of a 64-year-old woman with musculoskeletal pain and elevated serum parathyroid hormone who had undergone parathyroidectomy for primary hyperparathyroidism 4 years earlier. An 18 F-choline PET/CT scan was performed and incidentally showed an intense uptake in a right upper lobe pulmonary nodule and in the right hilar, mediastinal, and cervical lymph nodes. Histopathological analysis confirmed the diagnosis of a small cell lung cancer. Clinical symptoms and recurrent hyperparathyroidism were therefore consistent with a paraneoplastic syndrome. A complete metabolic response was achieved on 18 F-FDG PET/CT scan after chemotherapy.
Endoscopic ultrasonography-guided hybrid rendezvous technique for pancreatic stenting in a patient with pancreatoduodenectomy
Authors: Shinichi Hashimoto, Shiroh Tanoue, Yusuke Fujino, Makoto Hinokuchi, Hiromichi Iwaya, Shiho Arima, Akio Ido
Journal: Endoscopy (2020)

The endoscopic ultrasonography (EUS)-guided rendezvous technique is used in patients who previously underwent a pancreatoduodenectomy. This procedure facilitates recognition of the orifice of the pancreatic duct (PD), allows for cannulation of the obstructed PD [1] [2], and can be reattempted if the guidewire is dropped. The EUS-guided hybrid rendezvous technique is reported as an advanced technique for biliary drainage [3]. Here, we report that the technique was useful for PD drainage.
Allosteric SHP2 Inhibitor, IACS-13909, Overcomes EGFR-Dependent and EGFR-Independent Resistance Mechanisms toward Osimertinib
Authors: Yuting Sun, Brooke A. Meyers, Barbara Czako, Paul Leonard, Faika Mseeh, Angela L. Harris, Qi Wu, Sarah Johnson, Connor A. Parker, Jason B. Cross, Maria Emilia Di Francesco, Benjamin J. Bivona, Christopher A. Bristow, Jason P. Burke, Caroline C. Carrillo, Christopher L. Carroll, Qing Chang, Ningping Feng, Guang Gao, Sonal Gera, Virginia Giuliani, Justin K. Huang, Yongying Jiang, Zhijun Kang, Jeffrey J. Kovacs, Chiu-Yi Liu, Anastasia M. Lopez, Xiaoyan Ma, Pijus K. Mandal, Timothy McAfoos, Meredith A. Miller, Robert A. Mullinax, Michael Peoples, Vandhana Ramamoorthy, Sahil Seth, Nakia D. Spencer, Erika Suzuki, Christopher C. Williams, Simon S. Yu, Andy M. Zuniga, Giulio F. Draetta, Joseph R. Marszalek, Timothy P. Heffernan, Nancy E. Kohl, Philip Jones
Journal: Cancer Research (2020)

Src homology 2 domain-containing phosphatase (SHP2) is a phosphatase that mediates signaling downstream of multiple receptor tyrosine kinases (RTK) and is required for full activation of the MAPK pathway. SHP2 inhibition has demonstrated tumor growth inhibition in RTK-activated cancers in preclinical studies. The long-term effectiveness of tyrosine kinase inhibitors such as the EGFR inhibitor (EGFRi), osimertinib, in non-small cell lung cancer (NSCLC) is limited by acquired resistance. Multiple clinically identified mechanisms underlie resistance to osimertinib, including mutations in EGFR that preclude drug binding as well as EGFR-independent activation of the MAPK pathway through alternate RTK (RTK-bypass). It has also been noted that frequently a tumor from a single patient harbors more than one resistance mechanism, and the plasticity between multiple resistance mechanisms could restrict the effectiveness of therapies targeting a single node of the oncogenic signaling network. Here, we report the discovery of IACS-13909, a specific and potent allosteric inhibitor of SHP2, that suppresses signaling through the MAPK pathway. IACS-13909 potently impeded proliferation of tumors harboring a broad spectrum of activated RTKs as the oncogenic driver. In EGFR-mutant osimertinib-resistant NSCLC models with EGFR-dependent and EGFR-independent resistance mechanisms, IACS-13909, administered as a single agent or in combination with osimertinib, potently suppressed tumor cell proliferation
Association of Sleep Duration and Variability With Body Mass Index
Authors: Stuti J. Jaiswal, Giorgio Quer, Michael Galarnyk, Steven R. Steinhubl, Eric J. Topol, Robert L. Owens
Journal: JAMA Internal Medicine (2020)

This cohort study examines sleep and demographic data from wearable activity tracking devices to assess for an association of sleep duration and variability with body mass index.