tbuckley/cabot-search huggingface dataset:
Assessment of Lung Cancer Screening Program Websites
Authors: Stephen D. Clark, Daniel S. Reuland, Chineme Enyioha, Daniel E. Jonas
Journal: JAMA Internal Medicine (2020)

<h3>Importance</h3> The US Preventive Services Task Force recommends that individuals at high risk for lung cancer consider benefits and harms before pursuing lung cancer screening. Medical centers develop websites for their lung cancer screening programs, but to date little is known about the websites' portrayal of benefits and harms or what next steps they recommend for individuals considering screening. <h3>Objective</h3> To assess the presentation of potential benefits and harms and recommended next steps on lung cancer screening program websites. <h3>Design, Setting, and Participants</h3> Cross-sectional content analysis of 162 lung cancer screening program websites of academic medical centers (n = 81) and state-matched community medical centers (n = 81) that were randomly selected from American College of Radiology lung cancer screening–designated centers was conducted. The study was performed from December 1, 2018, to January 31, 2019. <h3>Main Outcomes and Measures</h3> Website presentation of screening-associated benefits and harms was the primary outcome. Benefit was defined as any description related to the potential reduction in lung cancer mortality. Harms were based on the US Preventive Services Task Force recommendations and included false positives, false negatives, overdiagnosis, radiation exposure, and incidental findings. The secondary outcome was next steps that are recommended by websites. <h3>Results</h3> Overall, the 162 lung cancer screening program websites described the potential benefits more frequently than they described any potential harms (159 [98%] vs 78 [48%],<i>P</i> &lt; .01). False-positive findings were the most frequently reported (72 [44%]) potential harm. Community centers were less likely than academic centers to report any potential harm (32 [40%] vs 46 [57%],<i>P</i> = .03), potential harm from radiation (20 [25%] vs 35 [43%],<i>P</i> = .01), and overdiagnosis (0% vs 11 [14%],<i>P</i> &lt; .01). One hundred nineteen websites (73%) did not explicitly recommend that individuals personally consider the potential benefits and harms of screening; community centers were less likely than academic centers to give this recommendation (15 [19%] vs 28 [35%],<i>P</i> = .02). Most institutions (157 [97%]) listed follow-up steps for screening, but few institutions (35 [22%]) recommended that individuals discuss benefits and harms with a health care professional. <h3>Conclusions and Relevance</h3> Information on public-facing websites of US lung cancer screening programs appears to lack balance with respect to portrayal of potential benefits and harms of screening. Important harms, such as overdiagnosis, were commonly ignored in the sites evaluated, and most of the centers did not explicitly guide individuals toward a guideline-recommended, shared decision-making discussion of harms and benefits.
Plasma microparticles of sickle patients during crisis or taking hydroxyurea modify endothelium inflammatory properties
Authors: Yohann Garnier, Séverine Ferdinand, Marie Garnier, Kizzy-Clara Cita, Régine Hierso, Aurélie Claes, Philippe Connes, Marie-Dominique Hardy-Dessources, Claudine Lapouméroulie, Nathalie Lemonne, Maryse Etienne-Julan, Wassim El Nemer, Marc Romana
Journal: Blood (2020)
Mechanism of Action of TiO<sub>2</sub>: Recommendations to Reduce Uncertainties Related to Carcinogenic Potential
Authors: Hedwig M. Braakhuis, Ilse Gosens, Minne B. Heringa, Agnes G. Oomen, Rob J. Vandebriel, Monique Groenewold, Flemming R. Cassee
Journal: The Annual Review of Pharmacology and Toxicology (2020)

The Risk Assessment Committee of the European Chemicals Agency issued an opinion on classifying titanium dioxide (TiO2) as a suspected human carcinogen upon inhalation. Recent animal studies indicate that TiO2 may be carcinogenic through the oral route. There is considerable uncertainty on the carcinogenicity of TiO2, which may be decreased if its mechanism of action becomes clearer. Here we consider adverse outcome pathways and present the available information on each of the key events (KEs). Inhalation exposure to TiO2 can induce lung tumors in rats via a mechanism that is also applicable to other poorly soluble, low-toxicity particles. To reduce uncertainties regarding human relevance, we recommend gathering information on earlier KEs such as oxidative stress in humans. For oral exposure, insufficient information is available to conclude whether TiO2 can induce intestinal tumors. An oral carcinogenicity study with well-characterized (food-grade) TiO2 is needed, including an assessment of toxicokinetics and early KEs.
Novel neuroprotective therapy with NeuroHeal by autophagy induction for damaged neonatal motoneurons
Authors: David Romeo-Guitart, César Marcos-DeJuana, Sara Marmolejo-Martínez-Artesero, Xavier Navarro, Caty Casas
Journal: Theranostics (2020)

Rationale: Protective mechanisms allow healthy neurons to cope with diverse stresses.Excessive damage as well as aging can lead to defective functioning of these mechanisms.We recently designed NeuroHeal using artificial intelligence with the goal of bolstering endogenous neuroprotective mechanisms.Understanding the key nodes involved in neuroprotection will allow us to identify even more effective strategies for treatment of neurodegenerative diseases.Methods: We used a model of peripheral nerve axotomy in rat pups, that induces retrograde apoptotic death of motoneurons.Nourishing mothers received treatment with vehicle, NeuroHeal or NeuroHeal plus nicotinamide, an inhibitor of sirtuins, and analysis of the pups were performed by immunohistochemistry, electron microscopy, and immunoblotting.In vitro, the post-translational status of proteins of interest was detailed using organotypic spinal cord cultures and genetic modifications in cell lines to unravel the neuroprotective mechanisms involved.Results: We found that the concomitant activation of the NAD + -dependent deacetylase SIRT1 and the PI3K/AKT signaling pathway converge to increase the presence of deacetylated and phosphorylated FOXO3a, a transcription factor, in the nucleus.This favors the activation of autophagy, a pro-survival process, and prevents pro-apoptotic PARP1/2 cleavage.Major conclusion: NeuroHeal is a neuroprotective agent for neonatal motoneurons that fine-tunes autophagy on by converging SIRT1/AKT/FOXO3a axis.NeuroHeal is a combo of repurposed drugs that allow its readiness for prospective pediatric use.
Absence of tongue papillae as a clinical criterion for the diagnosis of generalized recessive dystrophic epidermolysis bullosa types
Authors: Susanne Krämer, Ignacia Fuentes, María Joao Yubero, Carolina Encina, José Farfán, Ignacio Araya, Jimena Castillo Bennett, Constanza Fuentes, María Elena McNab, Gisela Zillmann, Marcelo Valle, Anne W. Lucky, Francis Palisson
Journal: Journal of the American Academy of Dermatology (2020)
Structure of the Native Muscle-type Nicotinic Receptor and Inhibition by Snake Venom Toxins
Authors: Md. Mahfuzur Rahman, Jinfeng Teng, Brady T. Worrell, Colleen M. Noviello, Myeongseon Lee, Arthur Karlin, Michael H.B. Stowell, Ryan E. Hibbs
Journal: Neuron (2020)
Abstract 367: Ventricular Assist Device Association in Improving Outcomes in Patients Resuscitated From Out of Hospital Cardiac Arrest
Authors: Julie Tram, Andrew Pressman, Nai-Wei Chen, David Berger, Joseph B Miller, Robert D Welch, Joshua C Reynolds, James M PRIBBLE, Ronny Otero, Robert A SWOR
Journal: Circulation (2019)

Introduction: There has been continued debate and limited research on the efficacy of ventricular assist devices such as intra-aortic balloon pumps and Impella devices on improving survival outcomes in post cardiac arrest patients. Objective: The primary objective of this study is to assess whether the use of ventricular assist devices is associated with improved survival outcome in patients resuscitated from out-of-hospital cardiac arrest in Michigan. Methods: We matched cardiac arrest cases from 2014-2017 in the Michigan CARES Registry (CARES) and the Michigan Inpatient Database (MIDB) using probabilistic linkage. Ventricular assist devices (VAD) are defined as either Intra-aortic balloon pump (IABP) or Impella device identified using ICD-9 or 10 procedure codes. Multilevel, multivariable regression analyses were employed to evaluate the impact of device use on survival to hospital discharge, adjusting for variables normally predictive of cardiac arrest survival (age, location, witnessed, shockable rhythm). Results: A total of 3,790 CARES cases were matched with the MIDB of which 183 (4.8%) received IABP, 50 (1.3%) received impella devices, and 1,131 (29.8%) survived to hospital discharge. VAD use was associated with improved survival to discharge (OR=2.07, 95% CI 1.55, 2.77). IABP were used more frequently and associated with an improved outcome (OR=2.16, 95%CI 1.59, 2.93) compared to the Impella device (OR=1.72, 95% CI 0.96, 3.06). In a multivariable model, however, VAD use was no longer associated with an improved outcome (aOR =0.95, 95% CI 0.69, 1.31). In the subset of patients with a diagnosis of cardiogenic shock (n=725) we identified an improved survival to discharge with VAD use (OR= 1.84 95% CI 1.24, 2.73). IABP use was more frequent and associated with an improved outcome (OR=1.98, 95% CI 1.32, 2.98). After adjusting for patient characteristics, VAD use increased the odds of an improved outcome by 14% but was not statistically significant (aOR = 1.14, 95% CI 0.74, 1.77 ). Conclusion: Although limited by a low frequency of use, VAD or IABP alone was associated with improved outcome for post arrest care. However, in a multivariable analysis, VAD use was not associated with an independent improvement in post arrest survival.
H2A Monoubiquitination Links Glucose Availability to Epigenetic Regulation of the Endoplasmic Reticulum Stress Response and Cancer Cell Death
Authors: Yilei Zhang, Jiejun Shi, Xiaoguang Liu, Zhenna Xiao, Guang Lei, Hyemin Lee, Pranavi Koppula, Weijie Cheng, Chao Mao, Li Zhuang, Li Ma, Wei Li, Boyi Gan
Journal: Cancer Research (2020)

Abstract Epigenetic regulation of gene transcription has been shown to coordinate with nutrient availability, yet the mechanisms underlying this coordination remain incompletely understood. Here, we show that glucose starvation suppresses histone 2A K119 monoubiquitination (H2Aub), a histone modification that correlates with gene repression. Glucose starvation suppressed H2Aub levels independently of energy stress–mediated AMP-activated protein kinase activation and possibly through NADPH depletion and subsequent inhibition of BMI1, an integral component of polycomb-repressive complex 1 (PRC1) that catalyzes H2Aub on chromatin. Integrated transcriptomic and epigenomic analyses linked glucose starvation–mediated H2Aub repression to the activation of genes involved in the endoplasmic reticulum (ER) stress response. We further showed that this epigenetic mechanism has a role in glucose starvation–induced cell death and that pharmacologic inhibition of glucose transporter 1 and PRC1 synergistically promoted ER stress and suppressed tumor growth in vivo. Together, these results reveal a hitherto unrecognized epigenetic mechanism coupling glucose availability to the ER stress response. Significance: These findings link glucose deprivation and H2A ubiquitination to regulation of the ER stress response in tumor growth and demonstrate pharmacologic susceptibility to inhibition of polycomb and glucose transporters.
A Genome-Wide Association Study Identifies Two Novel Susceptible Regions for Squamous Cell Carcinoma of the Head and Neck
Authors: Sanjay Shete, Hongliang Liu, Jian Wang, Robert Yu, Erich M. Sturgis, Guojun Li, Kristina R. Dahlstrom, Zhensheng Liu, Christopher I. Amos, Qingyi Wei
Journal: Cancer Research (2020)

Abstract To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which, 434,839 typed and 7,423,250 imputed SNPs were used as the discovery. SNPs with P &amp;lt; 1 × 10−3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from databases of Genotypes and Phenotypes. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96 × 10−9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54 × 10−9 for the leading SNP rs142021700) was identified for hypopharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and expression quantitative trait loci analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of human leukocyte antigen loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN. Significance: Two novel risk loci for SCCHN in non-Hispanic white individuals highlight the importance of immunologic mechanism in the disease etiology.
CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan, China
Authors: Heng Meng, Rui Xiong, Ruyuan He, Weichen Lin, Bo Hao, Lin Zhang, Zilong Lu, Xiaokang Shen, Tao Fan, Wenyang Jiang, Wenbin Yang, Tao Li, Jun Chen, Qing Geng
Journal: Journal of Infection (2020)

PurposeAimed to characterize the CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia.MethodsAsymptomatic cases with COVID-19 pneumonia confirmed by SARS-COV-2 nucleic acid testing in Renmin Hospital of Wuhan University were retrospectively enrolled. The characteristics of CT imaging and clinical feature were collected and analyzed.Results58 asymptomatic cases with COVID-19 pneumonia admitted to our hospital between Jan 1, 2020 and Feb 23, 2020 were enrolled. All patients had history of exposure to SARS-CoV-2. On admission, patients had no symptoms and laboratory findings were normal. The predominant feature of CT findings in this cohort was ground glass opacity (GGO) (55, 94.8%) with peripheral (44, 75.9%) distribution, unilateral location (34, 58.6%) and mostly involving one or two lobes (38, 65.5%), often accompanied by characteristic signs. After short-term follow-up, 16 patients (27.6%) presented symptoms with lower lymphocyte count and higher CRP, mainly including fever, cough and fatigue. The evolution of lesions on CT imaging were observed in 10 patients (17.2%). The average days of hospitalization was19.80±10.82 days, and was significantly longer in progression patients (28.60±7.55 day).ConclusionCT imaging of asymptomatic cases with COVID-19 pneumonia has definite characteristics. Since asymptomatic infections as "covert transmitter", and some patients can progress rapidly in the short term. It is essential to pay attention to the surveillance of asymptomatic patients with COVID-19. CT scan has great value in screening and detecting patients with COVID-19 pneumonia, especially in the highly suspicious, asymptomatic cases with negative nucleic acid testing.
Abstract 17245: A Novel Zebrafish Model of Human A-Band Truncated Titin Exhibits Altered Ventricular Diastolic Compliance in-vivo and Reveals Enhanced Susceptibility to the Effects of Volume Overload in Mutation Carriers
Authors: Louis W Wang, Inken G Huttner, Celine F Santiago, Renee Johnson, Claire Horvat, Wolfgang A Linke, Michael P Feneley, Diane Fatkin
Journal: Circulation (2017)

Introduction: Truncating variants in the TTN gene (TTNtv) encoding the sarcomeric protein, titin, are a major genetic risk factor for dilated cardiomyopathy (DCM). We studied 2 kindreds with famili...
Public Health Interventions for COVID-19
Authors: David M. Hartley, Eli N. Perencevich
Journal: JAMA (2020)

An Pan, PhD; Li Liu, MD, PhD; Chaolong Wang, PhD; Huan Guo, MD, PhD; Xingjie Hao, PhD; Qi Wang, MD, PhD; Jiao Huang, PhD; Na He, PhD; Hongjie Yu, PhD; Xihong Lin, PhD; Sheng Wei, MD, PhD; Tangchun Wu, MD, PhD
Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak
Authors: Mengyuan Dai, Dianbo Liu, Miao Liu, Fuxiang Zhou, Guiling Li, Zhen Chen, Zhian Zhang, Hua You, Meng Wu, Qichao Zheng, Yong Xiong, Huihua Xiong, Chun Wang, Changchun Chen, Fei Xiong, Yan Zhang, Yaqin Peng, Siping Ge, Bo Zhen, Tingting Yu, Ling Wang, Hua Wang, Yu Liu, Yeshan Chen, Junhua Mei, Xiaojia Gao, Zhuyan Li, Lijuan Gan, Can He, Zhen Li, Yuying Shi, Yuwen Qi, Jing Yang, Daniel G. Tenen, Li Chai, Lorelei A. Mucci, Mauricio Santillana, Hongbing Cai
Journal: Cancer Discovery (2020)

Abstract The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 is needed. We performed a multicenter study including 105 patients with cancer and 536 age-matched noncancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematologic cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Patients with nonmetastatic cancer experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, whereas patients who underwent only radiotherapy did not demonstrate significant differences in severe events when compared with patients without cancer. These findings indicate that patients with cancer appear more vulnerable to SARS-CoV-2 outbreak. Significance: Because this is the first large cohort study on this topic, our report will provide much-needed information that will benefit patients with cancer globally. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients. This article is highlighted in the In This Issue feature, p. 747
Differential Associations of Chronic Inflammatory Diseases With Incident Heart Failure
Authors: Sameer Prasada, Adovich Rivera, Arvind Nishtala, Anna E. Pawlowski, Arjun Sinha, Joshua D. Bundy, Simran A. Chadha, Faraz S. Ahmad, Sadiya S. Khan, Chad Achenbach, Frank J. Palella, Rosalind Ramsey-Goldman, Yvonne C. Lee, Jonathan I. Silverberg, Babafemi O. Taiwo, Sanjiv J. Shah, Donald M. Lloyd-Jones, Matthew J. Feinstein
Journal: JACC Heart Failure (2020)

The purpose of this study was to compare the risks of incident heart failure (HF) among a variety of chronic inflammatory diseases (CIDs) and to determine whether risks varied by severity of inflammation within each CID. Individuals with CIDs are at elevated risk for cardiovascular diseases, but data are limited regarding risk for HF. An electronic health records database from a large urban medical system was examined, comparing individuals with CIDs with frequency-matched controls without CIDs, all of whom were receiving regular outpatient care. Rates of incident HF were determined by using the Kaplan-Meier method and subsequently used multivariate-adjusted proportional hazards models to compare HF risks for each CID. Exploratory analyses determined HF risks by proxy measurement of CID severity. Of 37,636 patients (n = 18,278 patients with CIDs; and n = 19,358 controls without CIDs) there were 960 incident HF cases over a median of 3.6 years. Risks for incident HF were significantly or borderline significantly elevated for patients with systemic sclerosis (hazard ratio [HR]: 7.26; 95% confidence interval [CI]: 5.72 to 9.21; p < 0.01), systemic lupus erythematosus (HR: 3.15; 95% CI: 2.41 to 4.11; p < 0.01), rheumatoid arthritis (HR: 1.39; 95% CI: 1.13 to 1.71; p < 0.01), and human immunodeficiency virus (HR: 1.28; 95% CI: 0.99 to 1.66; p = 0.06). There was no association between psoriasis or inflammatory bowel disease and incident HF, although patients with those CIDs with higher levels of C-reactive protein had higher risks for HF than controls. Systemic sclerosis and systemic lupus erythematosus were associated with the highest risks of HF, followed by rheumatoid arthritis and HIV. Measurements of inflammation were associated with HF risk across different CIDs.
Utility of hyposmia and hypogeusia for the diagnosis of COVID-19
Authors: François Bénézit, Paul Le Turnier, Charles Declerck, Cécile Paillé, Matthieu Revest, Vincent Dubée, Pierre Tattevin, Cédric Arvieux, Marion Baldeyrou, Jean-Marc Chapplain, Pauline Comacle, Solène Patrat-Delon, Anne Maillard, Mélanie Poinot, Charlotte Pronier, Faouzi Souala, Vincent Thibault, Pierre Abgueguen, Hélène Cormier, Valérie Delbos, Marine de la Chapelle, Alexandra Ducancelle, Rafael Mahieu, Valérie Rabier, Sami Rehaiem, Yves Vandamme, Charlotte Biron, Jeanne Brochon, David Boutoille, Marie Chauveau, Colin Deschanvres, Benjamin J Gaborit, Joël Jenvrin, Raphaël Lecomte, Maeva Lefebvre, François Raffi
Journal: The Lancet Infectious Diseases (2020)
Telomere Maintenance Mechanisms Define Clinical Outcome in High-Risk Neuroblastoma
Authors: Balakrishna Koneru, Gonzalo Lopez, Ahsan Farooqi, Karina L. Conkrite, Thinh H. Nguyen, Shawn J. Macha, Apexa Modi, Jo Lynne Rokita, Eduardo Urias, Ashly Hindle, Heather Davidson, Kristyn Mccoy, Jonas Nance, Vanda Yazdani, Meredith S. Irwin, Shengping Yang, David A. Wheeler, John M. Maris, Sharon J. Diskin, C. Patrick Reynolds
Journal: Cancer Research (2020)

Abstract Neuroblastoma is a childhood cancer with heterogeneous clinical outcomes. To comprehensively assess the impact of telomere maintenance mechanism (TMM) on clinical outcomes in high-risk neuroblastoma, we integrated the C-circle assay [a marker for alternative lengthening of telomeres (ALT)], TERT mRNA expression by RNA-sequencing, whole-genome/exome sequencing, and clinical covariates in 134 neuroblastoma patient samples at diagnosis. In addition, we assessed TMM in neuroblastoma cell lines (n = 104) and patient-derived xenografts (n = 28). ALT was identified in 23.4% of high-risk neuroblastoma tumors and genomic alterations in ATRX were detected in 60% of ALT tumors; 40% of ALT tumors lacked genomic alterations in known ALT-associated genes. Patients with high-risk neuroblastoma were classified into three subgroups (TERT-high, ALT+, and TERT-low/non-ALT) based on presence of C-circles and TERT mRNA expression (above or below median TERT expression). Event-free survival was similar among TERT-high, ALT+, or TERT-low/non-ALT patients. However, overall survival (OS) for TERT-low/non-ALT patients was significantly higher relative to TERT-high or ALT patients (log-rank test; P &amp;lt; 0.01) independent of current clinical and molecular prognostic markers. Consistent with the observed higher OS in patients with TERT-low/non-ALT tumors, continuous shortening of telomeres and decreasing viability occurred in low TERT–expressing, non-ALT patient-derived high-risk neuroblastoma cell lines. These findings demonstrate that assaying TMM with TERT mRNA expression and C-circles provides precise stratification of high-risk neuroblastoma into three subgroups with substantially different OS: a previously undescribed TERT-low/non-ALT cohort with superior OS (even after relapse) and two cohorts of patients with poor survival that have distinct molecular therapeutic targets. Significance: These findings assess telomere maintenance mechanisms with TERT mRNA and the ALT DNA biomarker C-circles to stratify neuroblastoma into three groups, with distinct overall survival independent of currently used clinical risk classifiers.