tbuckley/cabot-search huggingface dataset:
Triassic Cancer—Osteosarcoma in a 240-Million-Year-Old Stem-Turtle
Authors: Yara Haridy, Florian Witzmann, Patrick Asbach, Rainer R. Schoch, Nadia Fröbisch, Bruce M. Rothschild
Journal: JAMA Oncology (2019)

Triassic Cancer-Osteosarcoma in a 240-Million-Year-Old Stem-Turtle Paleopathology, the study of ancient disease, is a vital way by which we understand the evolution of pathogens, immune systems, healing physiology, and ultimately the environment.Cancer research has focused on its prevalence in various organisms and has found that although some animals have a high propensity for cancer, 1 others seem to be resistant. 2The prevalence of cancer in the tree of life is certainly interesting, but its antiquity should be regarded with equal interest considering the increase in human cancer, which has been related to environmental and genetic changes, and the extreme rarity of cancer in the fossil record. 3 This study documents bone cancer in a 240million-year-old reptilian amniote from the Triassic period, which adds an important data point to the history of cancer in tetrapod evolution.Herein, we present a case study of an osteosarcoma, a highly malignant bone tumor, on the femur of the shell-less stem-turtle Pappochelys rosinae 4 (Figure 1) from the middle Triassic period of present-day Germany.The appearance of the tumor on this specimen conforms with presentday periosteal osteosarcoma in humans.
Spatial and Temporal Mapping of Human Innate Lymphoid Cells Reveals Elements of Tissue Specificity
Authors: Naomi A. Yudanin, Frederike Schmitz, Anne-Laure Flamar, Joseph J.C. Thome, Elia Tait Wojno, Jesper B. Moeller, Melanie Schirmer, Isabel J. Latorre, Ramnik J. Xavier, Donna L. Farber, Laurel A. Monticelli, David Artis
Journal: Immunity (2019)
Risk Compensation and Clinical Decision Making — The Case of HIV Preexposure Prophylaxis
Authors: Julia L. Marcus, Kenneth A. Katz, Douglas S. Krakower, Sarah K. Calabrese
Journal: New England Journal of Medicine (2019)

Uptake of preexposure prophylaxis (PrEP) for HIV has been limited for multiple reasons, including low awareness. Clinicians' concerns that an increased sense of protection will lead to greater risk taking among PrEP users are another important factor.
Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer
Authors: Jason A. Efstathiou, Kent W. Mouw, Ewan A. Gibb, Yang Liu, Chin-Lee Wu, Michael R. Drumm, Jose Batista da Costa, Marguerite du Plessis, Natalie Q. Wang, Elai Davicioni, Felix Y. Feng, Roland Seiler, Peter C. Black, William U. Shipley, David T. Miyamoto
Journal: European Urology (2019)
Abstract 15255: Predicting the Risk of In-Hospital Cardiac Arrest in Real Time by Identification of Changes on Continuous Electrocardiographic Telemetry Monitoring Using Automated Algorithms
Authors: Duc H Do, Alan Kuo, Edward S Lee, David Mortara, Xiao Hu, Noel G Boyle
Journal: Circulation (2017)

Introduction: Despite advances, survival to discharge following in-hospital cardiac arrest (IHCA) remains less than 25%. Patients at risk of IHCA are often on continuous ECG monitoring, but no auto...
AHA/ACC Guidelines for Preventing Heart Attack and Death in Patients With Atherosclerotic Cardiovascular Disease: 2001 Update
Authors: Sidney C. Smith, Steven N. Blair, Robert O. Bonow, Lawrence M. Brass, Manuel D. Cerqueira, Kathleen Dracup, Valentin Fuster, Antonio Gotto, Scott M. Grundy, Nancy Houston Miller, Alice Jacobs, Daniel Jones, Ronald M. Krauss, Lori Mosca, Ira Ockene, Richard C. Pasternak, Thomas Pearson, Marc A. Pfeffer, Rodman D. Starke, Kathryn A. Taubert
Journal: Circulation (2001)

HomeCirculationVol. 104, No. 13AHA/ACC Guidelines for Preventing Heart Attack and Death in Patients With Atherosclerotic Cardiovascular Disease: 2001 Update
Multilevel omics: A next step on the way to understanding pulmonary arterial hypertension?
Authors: Jurjan Aman, G. Kees Hovingh
Journal: Thorax (2019)

Pulmonary arterial hypertension (PAH) remains a major cause of morbidity and mortality despite continuous efforts to increase our understanding of the underlying pathophysiology.1 As a matter of fact, little has changed in terms of our ability to treat this deadly disease since the introduction of the first vasodilator treatment two decades ago.2 3 Although three different classes of drugs are currently available, all converge on the same downstream event (ie, vasodilation). The fact that mortality is still high despite current therapy suggests that there are hitherto unknown mechanisms that determine the outcome. Omic approaches provide an unbiased method, and—being both inclusive and hierarchical—omics may help to prioritise candidate targets for development of novel drug classes.

In the current issue of Thorax ,4 Harbaum et al have combined metabolomic and proteomic studies to assess whether a specific lipoprotein composition is associated with clinical endpoints in patients with PAH. Using nuclear MR spectroscopy, 105 different lipoproteins were measured in the plasma of patients with idiopathic or hereditary PAH and correlated with survival. The study demonstrated association of PAH survival with three lipoproteins of the high-density lipoprotein (HDL) subclass 4, of which HDL-4-apolipoprotein A-2 (HDL-4-Apo A-2) showed the strongest association. Higher levels of HDL-4-Apo A-2 were …
The Variable Clinical Expressivity of Factor V Leiden, but Not of Prothrombin G20210A, Correlates with the Extent of the APC Response to In Vivo Thrombin Formation
Authors: Heiko Rühl, Christina Berens, Sara Reda, Franziska Isabelle Winterhagen, Jens Müller, Johannes Oldenburg, Peter Hanfland, Bernd Pötzsch
Journal: Blood (2018)
MORPHEUS: A phase Ib/II study platform evaluating the safety and clinical efficacy of cancer immunotherapy (CIT)–based combinations in gastrointestinal (GI) cancers.
Authors: Jayesh Desai, Jeremy S. Kortmansky, Neil Howard Segal, Marwan Fakih, Do-Youn Oh, Kyu-Pyo Kim, Osama E. Rahma, Andrew H. Ko, Hyun Cheol Chung, Maria Alsina, Kun-Huei Yeh, Shi Li, Nedal Jaffer Abdulla Al-Sakaff, Jilpa Patel, Hila Barak, Jun Wang, Xiaosong Zhang, Conrad Bleul, Edward Cha, Jeeyun Lee
Journal: Journal of Clinical Oncology (2019)

TPS467 Background: CIT has significant survival benefits across multiple tumor types, but durable response is experienced by only subsets of patients (pts). To extend clinical benefit to more pts, efficacious CIT combinations (combos) targeting multiple cancer immune escape mechanisms need to be identified. The MORPHEUS platform includes multiple ph Ib/II trials designed to identify early signals of safety and efficacy of CIT combos. Using a randomized trial design, multiple treatment (tx) arms are compared with a single control arm in each pt cohort. We present three GI-specific MORPHEUS trials, each assessing CIT combos that could concurrently enhance multiple aspects of the cancer immune response. Methods: The MORPHEUS trials described here are global, open-label, randomized, Ph Ib/II trials enrolling pts with pancreatic ductal adenocarcinoma (PDAC), gastric or gastroesophageal junction cancers or colorectal cancer (CRC). New arms with novel CIT combos (table) are opened as new txs become available, and arms with minimal efficacy or unacceptable toxicity are closed. Studies include multiple cohorts for pts receiving different lines of tx (1L and 2L PDAC and gastric; 3L CRC). Pts with loss of clinical benefit or unacceptable toxicity may be eligible to enroll in a different CIT combo arm. Primary endpoints include safety and investigator-assessed ORR (RECIST v1.1); secondary endpoints: PFS, OS, DCR and DOR. Clinical trial information: NCT03193190, NCT03281369, NCT03555149. [Table: see text]
Abstract A65: In vivo neutralization of IL-10 enhances the antitumor effects of a therapeutic vaccine against HPV-associated tumor
Authors: Jamile Ramos da Silva, Natiely Silva Sales, Mariangela de Oliveira Silva, Luana M. M. Aps, Luis Carlos de Souza Ferreira, Mariana de Oliveira Diniz
Journal: Clinical Cancer Research (2018)

Abstract Although experimental therapeutic vaccines against HPV-induced tumors are capable of activating systemic E6 and E7-specific CD8+ T cells and inducing high levels of antitumor protection in murine model, they do not always correlate with clinical efficacy once these vaccines are tested in clinical settings. This observed discrepancy can be attributed to an immunosuppressive microenvironment elicited by the tumor that limits the efficacy of immunotherapeutic approaches. Solid evidence shows that IL-10 cytokine secretion is a relevant mediator of tumor immune evasion mechanisms, which inhibits the function of CD8+ T cells. Our group has sought alternatives to potentiate the effect of a DNA-based therapeutic vaccine (pgDE7h), which encodes the HPV-16 E7 protein fused to the herpes simplex virus type 1 (HSV-1) glycoprotein D (gD), previously developed in our laboratory. The present study aimed to investigate the potential role of immunossupression restriction using a plasmid encoding the soluble IL-10 receptor (pIL10R) to enhance the pgDE7h vaccine potency in the control of tumors expressing HPV-16 E6 and E7 proteins in a murine model (TC-1 cells). Our results showed a tumor growth delay after combining the vaccine with pIL-10R. Additionally, the use of in vivo electroporation as the plasmids delivery method conferred a therapeutic protection of 90% and 60% when the animals were immunized 5 or 14 days after challenge, respectively. The combination of the plasmids was also capable of increasing substantially the numbers of activated E7-specific CD8+ T lymphocytes both systemically and at the tumor site. Altogether, the results obtained are promising for the development of new strategies to increase the antitumor therapeutic effects of the pgDE7h vaccine and may contribute to its use under clinical conditions. Note: This abstract was not presented at the conference. Citation Format: Jamile Ramos da Silva, Natiely Silva Sales, Mariangela de Oliveira Silva, Luana M. M. Aps, Luis Carlos de Souza Ferreira, Mariana de Oliveira Diniz. In vivo neutralization of IL-10 enhances the antitumor effects of a therapeutic vaccine against HPV-associated tumor [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A65.
Improving Value-Based Care for Left Ventricular Assist Device Therapy
Authors: Richa Agarwal, Joseph G. Rogers
Journal: JAMA Cardiology (2019)

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Genome-wide association study of monoclonal gammopathy of unknown significance (MGUS): comparison with multiple myeloma
Authors: Hauke Thomsen, Subhayan Chattopadhyay, Niels Weinhold, Pavel Vodicka, Ludmila Vodickova, Per Hoffmann, Markus M. Nöthen, Karl-Heinz Jöckel, Christian Langer, Roman Hajek, Göran Hallmans, Ulrika Pettersson-Kymmer, Claes Ohlsson, Florentin Späth, Richard Houlston, Hartmut Goldschmidt, Kari Hemminki, Asta Försti
Journal: Leukemia (2019)
Head Injury in Soccer: From Science to the Field; summary of the head injury summit held in April 2017 in New York City, New York
Authors: Margot Putukian, Ruben J Echemendia, George Chiampas, Jiri Dvorak, Bert Mandelbaum, Lawrence J Lemak, Don Kirkendall
Journal: British Journal of Sports Medicine (2019)

There has been an increased focus and awareness of head injury and sport-related concussion (SRC) across all sports from the medical and scientific communities, sports organisations, legislators, the media and the general population. Soccer, in particular, has been a focus of attention due to the popularity of the game, the frequency of SRC and the hypothesised effects of repetitive heading of the ball. Major League Soccer, US Soccer and the National Women's Soccer League jointly hosted a conference entitled, 'Head Injury in Soccer: From Science to the Field', on 21-22 April 2017 in New York City, New York. The mission of this conference was to identify, discuss and disseminate evidence-based science related to the findings and conclusions of the fifth International Conference on Concussion in Sport held by the Concussion in Sport Group and apply them to the sport of soccer. In addition, we reviewed information regarding the epidemiology and mechanism of head injuries in soccer at all levels of play, data regarding the biomechanics and effects of repetitive head impacts and other soccer-specific considerations. We discussed how to release the information raised during the summit to key stakeholders including athletes, parents, coaches and healthcare providers. We identified future areas for research and collaboration to enhance the health and safety of soccer (football) players.
Association of Clinical Epidemiologic Exposures and Overall Survival with Genome-Wide DNA Methylation Profiles in Acute Myeloid Leukemia: Analysis of the Mayo Clinic AML Epidemiology Cohort
Authors: César J. Torres-Gutierrez, Michael G. Heckman, Ryan A. Hlady, Rhett P. Ketterling, Lisa Z. Sproat, Kathryn E. Pearce, Elizabeth R. Lesser, Nancy N. Diehl, Laura E. Finn, Liuyan Jennifer Jiang, Keith D. Robertson, James R. Cerhan, James M. Foran
Journal: Blood (2018)
Real-world treatment characteristics for first-line therapy (1L) of advanced hepatocellular carcinoma (HCC) in Canada and Europe.
Authors: Sharlene Gill, Dena H Jaffe, Marc DeCongelio, Arnold N. DuBell, Jing Shi, Tami Wisniewski, Gwilym Thompson
Journal: Journal of Clinical Oncology (2019)

353 Background: Sorafenib is indicated for the treatment of HCC. This study captures and describes real-world use of 1L therapy for advanced unresectable or metastatic HCC across Canada and Europe. Methods: A retrospective, non-interventional survey of 278 physicians in Canada (7.5%) and Europe (92.5%) (France, Germany, Italy, Spain and UK) was conducted between Feb-Mar 2018. Clinical and treatment data were collected from medical charts for patients aged ≥18y, who initiated and completed systemic 1L treatment for HCC within 2 years of data collection, and a Child-Pugh [CP] A/B at 1L initiation. Descriptive statistics compared 1L systemic therapy, sorafenib vs. other. Results: 706 patients were included (n = 504 sorafenib; n = 202 other [83% chemotherapy; 10% targeted therapy; 7% checkpoint inhibitors]) with a mean age at 1L of 62.7±9.3y and 79% males. Comorbidities did not differ by sorafenib vs. other for alcoholism (33%), Hepatitis C (14%), and nonalcoholic steatohepatitis and/or nonalcoholic fatty liver disease (9%) but did for Hepatitis B (12% vs. 6%) and cirrhosis (31% vs. 18%) (both p &lt; 0.05). At diagnosis, more patients treated with sorafenib vs. other had portal vein invasion (56% vs. 35%, p &lt; 0.001). At 1L initiation, sorafenib patients had better performance status (PS) (ECOG 0-1: 80% vs. 67%, p &lt; 0.05) and preserved liver function (CP A: 58% vs. 47%, p &lt; 0.05). The results indicated that sorafenib was used less compared to other systemic therapies among those with poor performance (ECOG 2-4) and poor liver function (CP B) (71% vs. 83%, p = 0.068). Median treatment duration was shorter for sorafenib (2 vs. 4 months, p &lt; 0.001). The most common grade 3 adverse events were fatigue (9%), diarrhea (5%), and hand/foot skin reaction (4%). Conclusions: In this real-world chart survey of Canadian and European physicians, sorafenib remains the most commonly used 1L systemic therapy for advanced HCC. Patients treated with sorafenib were more likely to have cirrhotic liver disease, portal vein invasion, better PS and preserved liver function, but sorafenib use was not limited to CP A. Understanding determinants of 1L therapy is important as the treatment landscape of HCC is evolving to address unmet need.
Abstract 15704: Clinical Significance of Synthesized 18lead Electrocardiography for ST Elevation Myocardial Infarction
Authors: Shinya Wada, Noritoshi Ito, Hiroshi Fukunaga, Yasuhide Tsuda, Hideo Takahashi, Kei Hatori, Naoki Saito, Hojo Sasaki, Tatsuhiko Murase, Ken Nagao, Shiro Sasaguri
Journal: Circulation (2017)

Background: AHA scientific statement has reported that additional recordings from right-sided and posterior leads increase the diagnostic sensitivity for ST-elevation myocardial infarction (STEMI). However, those electrocardiography (ECG) leads have not been recorded routinely. The purpose of this study was to investigate whether synthesized 18-lead ECG, which enables recordings to be obtained from 6 synthesized leads (V3R, V4R, V5R, V7, V8 and V9) during standard 12-lead ECG, is useful for STEMI. Methods: In June 2015, we introduced routine use of synthesized 18-lead ECG for triage of emergency care in our emergency department (ED). ST-segment elevation or depression with at least 1 mm (0.1mV) in 2 or more contiguous leads defined positive as suspected acute coronary syndrome (ACS). The definitive diagnosis of ACS was made according to the Japanese Circulation Society guidelines. We investigated the impact of synthesized 18-lead ECG on STEMI when compared to standard 12-lead ECG. Results: Of the 11, 883 ...
Phosphatase 1 Nuclear Targeting Subunit Mediates Recruitment and Function of Poly (ADP-Ribose) Polymerase 1 in DNA Repair
Authors: Feifei Wang, Songli Zhu, Laura A. Fisher, Ling Wang, Nicholas J. Eurek, James K. Wahl, Li Lan, Aimin Peng
Journal: Cancer Research (2019)

PARP, particularly PARP1, plays an essential role in the detection and repair of DNA single-strand breaks and double-strand breaks. PARP1 accumulates at DNA damage sites within seconds after DNA damage to catalyze the massive induction of substrate protein poly ADP-ribosylation (PARylation). However, the molecular mechanisms underlying the recruitment and activation of PARP1 in DNA repair are not fully understood. Here we show that phosphatase 1 nuclear targeting subunit 1 (PNUTS) is a robust binding partner of PARP1. Inhibition of PNUTS led to strong accumulation of endogenous DNA damage and sensitized the cellular response to a wide range of DNA-damaging agents, implicating PNUTS as an essential and multifaceted regulator of DNA repair. Recruitment of PNUTS to laser-induced DNA damage was similar to that of PARP1, and depletion or inhibition of PARP1 abrogated recruitment of PNUTS to sites of DNA damage. Conversely, PNUTS was required for efficient induction of substrate PARylation after DNA damage. PNUTS bound the BRCA1 C-terminal (BRCT) domain of PARP1 and was required for the recruitment of PARP1 to sites of DNA damage. Finally, depletion of PNUTS rendered cancer cells hypersensitive to PARP inhibition. Taken together, our study characterizes PNUTS as an essential partner of PARP1 in DNA repair and a potential drug target in cancer therapy. SIGNIFICANCE: These findings reveal PNUTS as an essential functional partner of PARP1 in DNA repair and suggest its inhibition as a potential therapeutic strategy in conjunction with DNA-damaging agents or PARP inhibitors.See related commentary by Murai and Pommier, p. 2460.
Abstract P142: Light Smoking is Associated With Metabolic Syndrome Risk Factors in Chilean Young Adults
Authors: Evaline Cheng, Raquel Burrows, Paulina Correa-Burrows, Estela Blanco, Sheila Gahagan
Journal: Circulation (2018)

Background: Metabolic syndrome (MetS) is a cluster of risk factors for CVD and DM2 that includes abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. While cigarette smoking has been associated with MetS risk factors in adults, young adulthood is an under-studied, susceptible period for developing long-term morbidity and mortality related to MetS. Objective: This study aims to examine the association between cigarette smoking and MetS in Chilean young adults. We hypothesized that cigarette smoking, even at low levels of exposure (&lt; 30 per week), is associated with an increased risk of developing MetS in young adults. Methods: We studied 243 Chilean young adults who were part of infancy studies related to iron deficiency and recruited for a study of cardiovascular risk at age 16. Participant BMI, waist circumference, blood pressure, fasting serum glucose, cholesterol, triglycerides, and HDL were measured. MetS was defined using IDF and AHA/NHLBI criteria, and MetS risk z-scores were calculated using published equations. Participants self-reported smoking and drinking habits using standardized questionnaires. Logistic regressions examined associations between smoking and each MetS risk factor. All models were adjusted for sex, MetS at adolescence, and frequency of alcohol consumption. Results: Participants were mean 22.5 years old and 49.8% male (121 of 243). The prevalence of obesity and MetS was 24.3% (59 of 243) and 15.3% (37 of 243) respectively. Among smokers (125 of 243), mean age of smoking initiation was 14.6 years and mean consumption was smoking 28 cigarettes per week. Smokers had significantly higher fasting serum glucose levels, lower HDL, and higher MetS risk scores compared to non-smokers. Smoking was significantly associated with greater odds of fasting hyperglycemia (OR 2.41, CI 1.04 - 5.59) and low HDL (OR 1.87, CI 1.05 - 3.31). Conclusion: Cigarette smoking was associated with MetS risk factors, specifically fasting hyperglycemia and low HDL cholesterol levels, in a population-based sample of Chilean young adults. Since our sample had low levels of smoking exposure (&lt; 30 cigarettes per week), these risk factors may herald the onset of MetS associated with light cigarette smoking. Increased emphasis should be placed on preventing the initiation of smoking or promoting cessation during this crucial risk period.
Author Correction: Electrical fingerprint of the amygdala guides neurofeedback training for stress resilience
Authors: Jackob N. Keynan, Avihay Cohen, Gilan Jackont, Nili Green, Noam Goldway, Alexander Davidov, Yehudit Meir-Hasson, Gal Raz, Nathan Intrator, Eyal Fruchter, Keren Ginat, Eugene Laska, Marc Cavazza, Talma Hendler
Journal: Nature Human Behaviour (2019)
Derivation of Anthracycline and Anthraquinone Equivalence Ratios to Doxorubicin for Late-Onset Cardiotoxicity
Authors: Elizabeth A. M. Feijen, Wendy M. Leisenring, Kayla L. Stratton, Kirsten K. Ness, Helena J. H. van der Pal, Elvira C. van Dalen, Gregory T. Armstrong, Gregory J. Aune, Daniel M. Green, Melissa M. Hudson, Jacqueline Loonen, Kevin C. Oeffinger, Leslie L. Robison, Yutaka Yasui, Leontien C. M. Kremer, Eric J. Chow
Journal: JAMA Oncology (2019)

Anthracyclines are part of many effective pediatric cancer treatment protocols. Most pediatric oncology treatment groups assume that the hematologic toxicity of anthracycline agents is equivalent to their cardiotoxicity; for example, Children's Oncology Group substitution rules consider daunorubicin and epirubicin isoequivalent to doxorubicin, whereas mitoxantrone and idarubicin are considered 4 to 5 times as toxic as doxorubicin.