tbuckley/cabot-search huggingface dataset:
Multidrug-Resistant <i>Aspergillus fumigatus</i> Carrying Mutations Linked to Environmental Fungicide Exposure — Three States, 2010–2017
Authors: Karlyn D. Beer, Eileen C. Farnon, Seema Jain, Carol Jamerson, Sarah Lineberger, Jeffrey Miller, Elizabeth L. Berkow, Shawn R. Lockhart, Tom Chiller, Brendan R. Jackson
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

The environmental mold Aspergillus fumigatus is the primary cause of invasive aspergillosis. In patients with high-risk conditions, including stem cell and organ transplant recipients, mortality exceeds 50%. Triazole antifungals have greatly improved survival (1); however, triazole-resistant A. fumigatus infections are increasingly reported worldwide and are associated with increased treatment failure and mortality (2). Of particular concern are resistant A. fumigatus isolates carrying either TR34/L98H or TR46/Y121F/T289A genetic resistance markers, which have been associated with environmental triazole fungicide use rather than previous patient exposure to antifungals (3,4). Reports of these triazole-resistant A. fumigatus strains have become common in Europe (2,3), but U.S. reports are limited (5). Because of the risk posed to immunocompromised patients, understanding the prevalence of such isolates in patients is important to guide clinical and public health decision-making. In 2011, CDC initiated passive laboratory monitoring for U.S. triazole-resistant A. fumigatus isolates through outreach to clinical laboratories. This system identified five TR34/L98H isolates collected from 2016 to 2017 (6), in addition to two other U.S. isolates collected in 2010 and 2014 and reported in 2015 (5). Four of these seven isolates were reported from Pennsylvania, two from Virginia, and one from California. Three isolates were collected from patients with invasive pulmonary aspergillosis, and four patients had no known previous triazole exposure. A. fumigatus resistant to all triazole medications is emerging in the United States, and clinicians and public health personnel need to be aware that resistant infections are possible even in patients not previously exposed to these medications.
EBV/LMP-specific T cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation
Authors: Lauren P. McLaughlin, Rayne Rouce, Stephen Gottschalk, Vicky Torrano, George Carrum, Meng-Fen Wu, Fahmida Hoq, Bambi Grilley, Andrea M. Marcogliese, Patrick J. Hanley, Adrian P. Gee, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Catherine M. Bollard
Journal: Blood (2018)
Opportunities for improving cancer care management through primary care-oncology relationships.
Authors: Jennifer Tsui, Jenna Howard, William L. Miller, Denalee M. O'Malley, Shawna V. Hudson, Ellen Rubinstein, Alicja Bator, Benjamin F Crabtree
Journal: Journal of Clinical Oncology (2018)

80 Background: Improvements in the management of care transitions between primary care and oncology are critical for achieving optimal care quality and outcomes for cancer patients and survivors. We examine relationships between innovative PC practices and oncologists to inform and strengthen PC-oncology interfaces in diverse healthcare settings. Methods: Comparative case studies of 14 innovative PC practices throughout the United States examined strategies for providing cancer survivorship care. Field researchers observed each practice for 10-12 days, recording fieldnotes and conducting key informant and formal, semi-structured interviews with clinicians and staff. We extracted all data related to PC-oncology relationships and then collaboratively identified patterns to characterize these relationships through an inductive “immersion/crystallization” analysis process. Results: Nine of the 14 practices discussed either formal or informal PC-oncology relationships. Nearly all practices with existing formal PC-oncology relationships were embedded within healthcare systems. Private, independent practices had more informal relationships between individual PC physicians and specific oncologists. Practices with formal relationships noted ease of communication and transfer of patient information, timeliness in patient referrals, and direct access to oncologists; while practices with informal relationships noted the benefits of having close engagement with specific oncologists. Regardless of relationship type, remaining challenges include lack of clarity about roles during cancer treatment and beyond. Conclusions: With the rapid transformation of U.S. healthcare towards system ownership of primary care practices, efforts are needed to integrate the strengths of both formal and informal PC-oncology relationships to improve care for cancer patients and survivors.
Abstract 18427: 1-Hour Algorithm Based on High-Sensitivity Troponin I to Diagnose Type 1 Acute Myocardial Infarction
Authors: Johannes T Neumann, Nils A Sörensen, Francisco Ojeda, Tjark Schwemer, Tanja Zeller, Renate Schnabel, Mahir Karakas, Thomas Renne, Stefan Blankenberg, Dirk Westermann
Journal: Circulation (2016)

Background: There is a clinical need for early and accurate diagnosis of acute myocardial infarction (AMI). According to current ESC guidelines, the diagnosis of non-ST-elevation AMI is based on se...
Childhood parental death as a risk factor for lung cancer in the Shanghai Cohort Study.
Authors: Dana H. Bovbjerg, Carissa A. Low, Amy Elizabeth Lowery, Donna M. Posluszny, John E. Schmidt, Neomi Vin-Raviv, Yu-Tang Gao, Renwei Wang, Jian-Min Yuan
Journal: Journal of Clinical Oncology (2015)

e20577 Background: Accumulating evidence indicates that adverse childhood experiences (ACEs) substantially increase the risk of negative health behaviors and outcomes later in life. Multiple studies have documented that ACEs are associated with increased rates of cigarette smoking, but just one prospective study, with only 64 cases, reported an increased risk of lung cancer. Methods: The present study explored childhood ( < 12y) parental death, one of the most profoundly stressful ACEs, as a risk factor for adult cigarette smoking and lung cancer in the Shanghai Cohort Study, a population-based prospective cohort of 18,244 men aged 45-64 years in Shanghai, China, enrolled during 1986-1989. Information on parental death, smoking history, and other lifestyle factors were collected by trained nurse interviewers at baseline. Cancer incidence among cohort participants has been identified through annual in-person interviews and linkage analyses with databases of the Shanghai Cancer Registry and death index. After accrual of 348,249 person-years with up to 25 years of follow-up, 906 lung cancer cases have been identified. Hazard ratio (HR) and the corresponding 95% confidence intervals (CIs) were calculated using the Cox proportional hazard regression method adjusted for potential confounders. Results: Individuals who experienced childhood parental death had higher smoking rates with more cigarettes/day and years of smoking. Childhood parental death remained significantly associated with increased risk of lung cancer after adjustment for smoking and other potential confounders. The adjusted-HRs (95% CIs) for the death of father, mother, or both parents were 1.02 (0.85-1.23), 1.20 (0.95-1.52) and 1.44 (1.07-1.94), respectively, compared with those who did not experience childhood parental death (P for trend = 0.01). Conclusions: These findings suggest a long lasting adverse impact of parental death in childhood on the risk of developing lung cancer. The biological mechanisms responsible for the increased risk beyond smoking are not yet known, but ACEs have been shown to have profound effects on biological stress responses, which could contribute to increased oxidative DNA damage, a known risk factor for lung cancer.
Sex Differences in Faculty Rank Among Academic Cardiologists in the United States
Authors: Daniel M. Blumenthal, Andrew R. Olenski, Robert W. Yeh, Doreen DeFaria Yeh, Amy Sarma, Ada C. Stefanescu Schmidt, Malissa J. Wood, Anupam B. Jena
Journal: Circulation (2017)

Studies demonstrate that women physicians are less likely than men to be full professors. Comprehensive evidence examining whether sex differences in faculty rank exist in academic cardiology, adjusting for experience and research productivity, is lacking. Therefore, we evaluated for sex differences in faculty rank among a comprehensive, contemporary cohort of US cardiologists after adjustment for several factors that impact academic advancement, including measures of clinical experience and research productivity.We identified all US cardiologists with medical school faculty appointments in 2014 by using the American Association of Medical Colleges faculty roster and linked this list to a comprehensive physician database from Doximity, a professional networking website for doctors. Data on physician age, sex, years since residency, cardiology subspecialty, publications, National Institutes of Health grants, and registered clinical trials were available for all academic cardiologists. We estimated sex differences in full professorship, adjusting for these factors and medical school-specific fixed effects in a multivariable regression model.Among 3810 cardiologists with faculty appointments in 2014 (13.3% of all US cardiologists), 630 (16.5%) were women. Women faculty were younger than men (mean age, 48.3 years versus 53.5 years, P<0.001), had fewer total publications (mean number: 16.5 publications versus 25.2 publications; P<0.001), were similarly likely to have National Institutes of Health funding (proportion with at least 1 National Institutes of Health award, 10.8% versus 10.4%; P=0.77), and were less likely to have a registered clinical trial (percentage with at least 1 clinical trial, 8.9% versus 11.1%; P=0.10). Among 3180 men, 973 (30.6%) were full professors in comparison with 100 (15.9%) of 630 women. In adjusted analyses, women were less likely to be full professors than men (adjusted odds ratio, 0.63; 95% confidence interval, 0.43-0.94; P=0.02; adjusted proportions, 22.7% versus 26.7%; absolute difference, -4.0%; 95% confidence interval, -7.5% to -0.7%).Among cardiology faculty at US medical schools, women were less likely than men to be full professors after accounting for several factors known to influence faculty rank.
Abstract 15422: Genetic Predisposition to High Blood Pressure and Lifestyle: Associations With Midlife Blood Pressure Levels and Cardiovascular Health Outcomes
Authors: Raha Pazoki, Abbas Dehghan, Evangelos Evangelou, Helen Warren, He Gao, Marc Caulfield, Paul Elliott, Ioanna Tzoulaki
Journal: Circulation (2017)

Background: High blood pressure (BP) is a major risk factor of cardiovascular diseases (CVD); the leading cause of mortality worldwide. Both heritable and lifestyle risk factors contribute to eleva...
Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack
Authors: Lawrence H. Young, Catherine M. Viscoli, Jeptha P. Curtis, Silvio E. Inzucchi, Gregory G. Schwartz, Anne M. Lovejoy, Karen L. Furie, Mark J. Gorman, Robin Conwit, J. Dawn Abbott, Daniel L. Jacoby, Daniel M. Kolansky, Steven E. Pfau, Frederick S. Ling, Walter N. Kernan
Journal: Circulation (2017)

Insulin resistance is highly prevalent among patients with atherosclerosis and is associated with an increased risk for myocardial infarction (MI) and stroke. The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone decreased the composite risk for fatal or nonfatal stroke and MI in patients with insulin resistance without diabetes mellitus, after a recent ischemic stroke or transient ischemic attack. The type and severity of cardiac events in this population and the impact of pioglitazone on these events have not been described. We performed a secondary analysis of the effects of pioglitazone, in comparison with placebo, on acute coronary syndromes (MI and unstable angina) among IRIS participants. All potential acute coronary syndrome episodes were adjudicated in a blinded fashion by an independent clinical events committee. The study cohort was composed of 3876 IRIS participants, mean age 63 years, 65% male, 89% white race, and 12% with a history of coronary artery disease. Over a median follow-up of 4.8 years, there were 225 acute coronary syndrome events, including 141 MIs and 84 episodes of unstable angina. The MIs included 28 (19%) with ST-segment elevation. The majority of MIs were type 1 (94, 65%), followed by type 2 (45, 32%). Serum troponin was 10× to 100× upper limit of normal in 49 (35%) and >100× upper limit of normal in 39 (28%). Pioglitazone reduced the risk of acute coronary syndrome (hazard ratio, 0.71; 95% confidence interval, 0.54-0.94; P=0.02). Pioglitazone also reduced the risk of type 1 MI (hazard ratio, 0.62; 95% confidence interval, 0.40-0.96; log-rank P=0.03), but not type 2 MI (hazard ratio, 1.05; 95% confidence interval, 0.58-1.91; P=0.87). Similarly, pioglitazone reduced the risk of large MIs with serum troponin >100× upper limit of normal (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87; P=0.02), but not smaller MIs. Among patients with insulin resistance without diabetes mellitus, pioglitazone reduced the risk for acute coronary syndromes after a recent cerebrovascular event. Pioglitazone appeared to have its most prominent effect in preventing spontaneous type 1 MIs. URL: http://clinicaltrials.gov. Unique identifier: NCT00091949.
Clinical, dermoscopic and reflectance confocal microscopy characterization of facial basal cell carcinomas presenting as small white lesions on sun‐damaged skin
Authors: K. Liopyris, C. Navarrete‐Dechent, O. Yélamos, M. A. Marchetti, H. Rabinovitz, A. A. Marghoob
Journal: British Journal of Dermatology (2018)
Abstract 13585: The Relationship Between Dietary Magnesium Intake and Incident Heart Failure Among Older Women: The Women’s Health Initiative
Authors: Mengna Huang, Wen-Chih H Wu, Tracey H Taveira, Simin Liu, Mary B Roberts, Lisa W Martin, Gregory A Wellenius, Karen C Johnson, JoAnn E Manson, Charles B Eaton
Journal: Circulation (2015)

Background: Heart failure (HF) causes substantial burden and cost in older women. Low intake of dietary magnesium (Mg) has been associated with cardiac arrest, sudden cardiac death, fatal coronary heart disease, and stroke, although little is known about how Mg affects risk of HF. Methods: We included 88,752 postmenopausal women of the prospective Women’s Health Initiative-Observational Study (WHI-OS). Incident hospitalized HF was adjudicated by medical record abstraction of self-reported hospitalization. Dietary intake of Mg was measured at baseline by a 122-item validated semi-quantitative food frequency questionnaire. We adjusted dietary Mg intake with calibrated total energy using the residual method. Cox proportional hazards models were used to evaluate the association adjusting for potential confounding factors, including demographics, traditional risk factors, dietary intake, and Mg-containing medications and multivitamins. Additional analyses were conducted in the subset of all black and Hispanic participants and those in the hormone therapy trial of WHI, for whom HF cases were re-adjudicated and classified into HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). Since there are great differences in risk factors and pathology between the two subtypes of HF, we explored the potential different associations of dietary Mg with both in 40,969 participants of this subset. Results: Among participants in the OS, women in the lowest quartile of residual Mg intake (median: 154 mg/day) had 1.44 (95% CI: 1.11-1.86) times the hazard of incident HF compared to those in the highest quartile (median: 366 mg/day). Total Mg combining unadjusted dietary and supplemental Mg intake showed a similar but non-significant result (HR = 1.22, 95% CI: 0.98-1.51 comparing lowest to highest quartile). Low dietary Mg intake was also associated, although not significantly, with increased hazards of both HFpEF (hazard ratio (HR) = 1.42 comparing lowest to highest quartile, 95% CI: 0.92-2.18) and HFrEF (HR = 1.35 comparing lowest to highest quartile, 95% CI: 0.84-2.17). Conclusions: Low dietary Mg intake at baseline was associated with higher long-term risk of incident HF. Results were similar for incident HFpEF and HFrEF.
Abstract B70: Identification of reference genes for normalizing gene expression for RT-qPCR analysis in established cervical cancer cell lines and their derived cancer stem like cells
Authors: Rafael Paschoal de Campos, Iago Carvalho Schultz, Paola de Andrade Mello, Samuel Davies, Manuela Sangalli Gasparin, Ana Paula Santin Bertoni, Jéssica Gonçalves Azevedo, Andréia Buffon, Márcia Rosângela Wink
Journal: Clinical Cancer Research (2018)

Abstract Cervical cancer is the fourth most common cancer affecting women worldwide. Cancer stem cells are a subpopulation of tumor cells related to malignancy, resistance, and poor survival. Considering the importance of gene expression studies to understand cervical cancer stem cells (CCSC) biology and the need of proper validation of reference genes to normalize RT-qPCR data, this work identifies stable reference genes for the cervical cancer cell lines SiHa, HeLa, and ME180 as well as their respective derived cancer stem like cells. A literature review was performed to identify whether validation of reference genes was available for RT-qPCR assays in cervical cancer cell lines. Then cell lines were cultured in regular monolayer or in tumor sphere formation conditions. RT-PCR was carried out to validate cells grown as spheres as CCSC. RT-qPCR was performed using five commonly used reference genes: ACTB, B2M, GAPDH, HPRT1, and TBP. Stability was assessed through analysis of dispersion data and the Normfinder software to validate the selected genes as suitable reference genes. According to the literature review, no validation of reference genes for SiHa, HeLa, or ME180 cells in standard culture conditions or their CCSC subpopulations has been done so far. Our evaluation validated B2M, GAPDH, HPRT1, and TBP in these set conditions. Among them, GAPDH presented the lowest stability value (0.222), being therefore the most adequate gene to normalize the combination of all samples. Moreover, associating GAPDH and TBP led to a more stable value (0.184). These results suggest that B2M, GAPDH, HPRT1, and TBP are suitable reference genes to normalize RT-qPCR data of established cervical cancer cell lines SiHa, HeLa, and ME180 as well as their derived cancer stem like cells. Furthermore, GAPDH seems to be the most convenient choice for studying the combination of these cells. Citation Format: Rafael Paschoal de Campos, Iago Carvalho Schultz, Paola de Andrade Mello, Samuel Davies, Manuela Sangalli Gasparin, Ana Paula Santin Bertoni, Jéssica Gonçalves Azevedo, Andréia Buffon, Márcia Rosângela Wink. Identification of reference genes for normalizing gene expression for RT-qPCR analysis in established cervical cancer cell lines and their derived cancer stem like cells [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 B70.
Subversion of Systemic Glucose Metabolism as a Mechanism to Support the Growth of Leukemia Cells
Authors: Haobin Ye, Biniam Adane, Nabilah Khan, Erica Alexeev, Nichole Nusbacher, Mohammad Minhajuddin, Brett M. Stevens, Amanda C. Winters, Xi Lin, John M. Ashton, Enkhtsetseg Purev, Lianping Xing, Daniel A. Pollyea, Catherine A. Lozupone, Natalie J. Serkova, Sean P. Colgan, Craig T. Jordan
Journal: Cancer Cell (2018)
Malaria systems immunology: Plasmodium vivax induces tolerance during primary infection through dysregulation of neutrophils and dendritic cells
Authors: Andres F. Vallejo, Robert C. Read, Myriam Arevalo-Herrera, Sócrates Herrera, Tim Elliott, Marta E. Polak
Journal: Journal of Infection (2018)

Highlights•In silico analysis suggests that primary infection with P. vivax induces potent immunosuppression mediated by dendritic cells.•Antigen presentation is attenuated in malaria-experienced vs malaria-naïve individuals•Malaria induce immunosuppressive effect manifested with strong induction of IDO1.SummaryObjectivesTo dissect the transcriptional networks underpinning immune cells responses during primary Plasmodium vivax infection of healthy human adults.MethodsWe conducted network co-expression analysis of next-generation RNA sequencing data from whole blood from P. vivax and P. falciparum controlled human malaria infection (CHMI) of healthy naïve and malaria-exposed volunteers. Single cell transcription signatures were used to deconvolute the bulk RNA-Seq data into cell-specific signals.ResultsInitial exposure to P. vivax induced activation of innate immunity, including efficient antigen presentation and complement activation. However, this effect was accompanied by strong immunosuppression mediated by dendritic cells via the induction of Indoleamine 2,3-Dioxygenase 1(IDO1) and Lymphocyte Activation Gene 3 (LAG3). Additionally, P. vivax induced depletion of neutrophil populations associated with down regulation of 3G-protein coupled receptors, CRXCR1, CXCR2 and CSF3R. Accordingly, in malaria-exposed volunteers the inflammatory response was attenuated, with a decreased class II antigen presentation in dendritic cells. While the immunosuppressive signalling was maintained between plasmodium species, response to P. falciparum was significantly more immunogenic.ConclusionsIn silico analyses suggest that primary infection with P. vivax induces potent immunosuppression mediated by dendritic cells, conditioning subsequent anti-malarial immune responses. Targeting immune evasion mechanisms could be an effective alternative for improving vaccine efficacy.