1,085 results on '"N. MEYER"'
Search Results
2. Nefarious NTRK oncogenic fusions in pediatric sarcomas: Too many to Trk
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Megha R. Aepala, Malalage N. Peiris, Zian Jiang, Wei Yang, April N. Meyer, and Daniel J. Donoghue
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Oncogene Proteins, Fusion ,Neoplasms ,Endocrinology, Diabetes and Metabolism ,Immunology ,Biomarkers, Tumor ,Humans ,Immunology and Allergy ,Sarcoma ,Receptor, trkA ,Gene Fusion ,Child ,Protein Kinase Inhibitors ,General Biochemistry, Genetics and Molecular Biology - Abstract
Neurotrophic Tyrosine Receptor Kinase (NTRK) genes undergo chromosomal translocations to create novel open reading frames coding for oncogenic fusion proteins; the N-terminal portion, donated by various partner genes, becomes fused to the tyrosine kinase domain of either NTRK1, NTRK2, or NTRK3. NTRK fusion proteins have been identified as driver oncogenes in a wide variety of tumors over the past three decades, including Pediatric Gliomas, Papillary Thyroid Carcinoma, Spitzoid Neoplasms, Glioblastoma, and additional tumors. Importantly, NTRK fusions function as drivers of pediatric sarcomas, accounting for approximately 15% of childhood cancers including Infantile Fibrosarcoma (IFS), a subset of pediatric soft tissue sarcoma (STS). While tyrosine kinase inhibitors (TKIs), such as larotrectinib and entrectinib, have demonstrated profound results against NTRK fusion-positive cancers, acquired resistance to these TKIs has resulted in the formation of gatekeeper, solvent-front, and compound mutations. We present a comprehensive compilation of oncogenic fusions involving NTRKs focusing specifically on pediatric STS, examining their biological signaling pathways and mechanisms of activation. The importance of an obligatory dimerization or multimerization domain, invariably donated by the N-terminal fusion partner, is discussed using characteristic fusions that occur in pediatric sarcomas. In addition, examples are presented of oncogenic fusion proteins in which the N-terminal partners may contribute additional biological activities beyond an oligomerization domain. Lastly, therapeutic approaches to the treatment of pediatric sarcoma will be presented, using first generation and second-generation agents such as selitrectinib and repotrectinib.
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- 2022
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3. <scp>SCALP</scp> syndrome with a germline heterozygous DOCK6 mutation and somatic mosaic NRAS <scp>Q61R</scp> mutation
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Summer N. Meyer, Elanee M. Simmons, John D. McPherson, Smita Awasthi, and Maija Kiuru
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Pediatrics, Perinatology and Child Health ,Dermatology - Published
- 2022
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4. Public views on polygenic screening of embryos
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Michelle N. Meyer, Tammy Tan, Daniel J. Benjamin, David Laibson, and Patrick Turley
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Multidisciplinary - Abstract
Understanding moral acceptability and willingness to use is crucial for informing policy
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- 2023
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5. Human trafficking awareness and reporting: insights from Tennessee police websites and Twitter
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Ben Stickle, Teresa C. Kulig, Sadie Creel, Kayla N. Meyer, Bethany Maynard, and Garrett C. Jeanes
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Public Administration ,Law ,Pathology and Forensic Medicine - Abstract
PurposeHuman trafficking is challenging to address; one facet of response has been to engage with the public to increase awareness of trafficking and create connections that facilitate identification. Police officials are uniquely situated to engage with the community on human trafficking through their online presence. However, little is known about how police officials use these virtual platforms to discuss trafficking.Design/methodology/approachThe current study examines how Tennessee police use agency websites and Twitter to connect with their community on the issue of human trafficking.FindingsOut of 241 police agencies studied in Tennessee, 80% (n = 192) had websites, while 35% (n = 84) had Twitter accounts. Findings suggest that Tennessee agencies are not currently using websites (1%) or Twitter (4.7%) to engage with the public about human trafficking. Further, when it did occur, the communication to the public was limited in depth and resources.Research limitations/implicationsFuture research should include other police agencies and additional social media sites.Practical implicationsPolice agencies could be more proactive at engaging the community, with the caveat that any future initiatives should have clear goals and monitor their effectiveness at achieving their intended outcomes.Originality/valueThis research provides a fundamental analysis of how police agencies communicate to the public on issues related to human trafficking.
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- 2022
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6. Effect of intermittent access to alcohol mixed in energy drink during adolescence on alcohol self‐administration, anxiety, and memory during adulthood in rats
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Keith L. Williams, Urja K. Parikh, Shannon M. Doyle, and Lindsey N. Meyer
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Adult ,Adolescent ,Alcohol Drinking ,Ethanol ,Alcoholic Beverages ,Medicine (miscellaneous) ,Anxiety ,Toxicology ,Rats ,Rats, Sprague-Dawley ,Psychiatry and Mental health ,Animals ,Energy Drinks ,Humans ,Female - Abstract
Mixing alcohol with caffeinated energy drinks is a common practice among young people. Consumption of alcohol mixed in energy drink is associated with increased risk of binge drinking and alcohol dependence. The purpose of this study was to determine whether voluntary intermittent access to alcohol mixed in energy drink in adolescent rats alters adult self-administration of alcohol, anxiety, and memory.For 10 weeks in the home-cage, two groups of adolescent female Sprague-Dawley rats had intermittent access to energy drink (ED) or 10% alcohol mixed in energy drink (AmED) with water concurrently available. Other rat groups had daily continuous access to ED or AmED. Anxiety was measured with an open field test and memory was assessed with a novel place recognition test. For self-administration, rats pressed levers for 10% alcohol alone on a fixed ratio (FR1) and on a progressive ratio (PR).Intermittent access to AmED generated greater intake during the initial 30 min of access (AmED 1.70 ± 0.04 g/kg vs. ED 1.01 ± 0.06 g/kg) and during the subsequent 24 h (AmED 7.04 ± 0.25 g/kg vs. ED 5.60 ± 0.29 g/kg). Intermittent AmED caused a significant but small decrease in anxiety while neither ED nor AmED altered memory. During alcohol self-administration, group differences emerged only during PR testing during which intermittent AmED rats responded more than all other groups.These findings suggest that intermittent access to AmED generates binge-like consumption that supports human findings that AmED generates greater alcohol consumption. Furthermore, experience with AmED may alter the motivational properties of alcohol into adulthood without necessarily causing a major impact on anxiety or memory.
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- 2022
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7. Immunizations in Children With Chronic Diseases: A State of the Science Review With Implications for Practice Change
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Elishua L.B. Reingold, Miyuki Bennion, and Mary N. Meyer
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Parents ,Immunization Programs ,Chronic Disease ,Vaccination ,Pediatrics, Perinatology and Child Health ,Humans ,Immunization ,Child - Abstract
Chronic diseases afflict more than 25% of America's children, and it has been reported that some children with chronic illness are underimmunized, compounding their risks of complications from vaccine-preventable infections.To better assess vaccination rates in this population, we systematically reviewed PubMed and CINAHL. Publications were included if specific to immunization rates in U.S. children aged18 years and were published between 2010 and 2020. A total of 18 studies were reviewed.Compared with healthy children, children with chronic illnesses have significantly lower vaccination rates, and they face higher risks if they contract a preventable disease.Barriers to on-time vaccinations included inadequate education for both parents and providers and misconceptions from nonmedical sources. In addition, lack of provider comfort serves to lower vaccination rates of children with chronic illness. This topic requires further research and discussion until all children are protected from preventable illness.
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- 2022
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8. Chronic high-sugar diet in adulthood protects Caenorhabditis elegans from 6-OHDA induced dopaminergic neurodegeneration
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Katherine S Morton, Jessica S Hartman, Nathan Heffernan, Ian Ryde, Isabel W Kenny-Ganzert, Lingfeng Meng, David R Sherwood, and Joel N Meyer
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Article - Abstract
Background: Diets high in saturated fat and sugar, termed western diets, have been associated with several negative health outcomes, including increased risk for neurodegenerative disease. Parkinson s Disease (PD) is the second most prevalent neurodegenerative disease and is characterized by the progressive death of dopaminergic neurons in the brain. We build upon previous work characterizing the impact of high sugar diets in Caenorhabditis elegans to mechanistically evaluate the relationship between high sugar diets and dopaminergic neurodegeneration. Results: Non-developmental high glucose and fructose diets led to increased lipid content and shorter lifespan and decreased reproduction. However, in contrast to previous reports, we found that non-developmental chronic high-glucose and high-fructose diets did not induce dopaminergic neurodegeneration alone and were protective from 6-hydroxydopamine (6-OHDA) induced degeneration. Neither sugar altered baseline electron transport chain function, and both increased vulnerability to organism-wide ATP depletion when the electron transport chain was inhibited, arguing against energetic rescue as a basis for neuroprotection. The induction of oxidative stress by 6-OHDA is hypothesized to contribute to its pathology, and high sugar diets prevented this increase in the soma of the dopaminergic neurons. However, we did not find increased expression of antioxidant enzymes or glutathione levels. Instead, we found evidence suggesting alterations to dopamine transmission that could result in decreased 6-OHDA uptake. Conclusion: Our work uncovers a neuroprotective role for high sugar diets, despite concomitant decreases in lifespan and reproduction. Our results support the broader finding that ATP depletion alone is insufficient to induce dopaminergic neurodegeneration, whereas increased neuronal oxidative stress may drive degeneration. Finally, our work highlights the importance of evaluating lifestyle by toxicant interactions.
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- 2023
9. Safety and efficacy of the anti-PD1 immunotherapy with nivolumab in trichoblastic carcinomas
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E. Toulemonde, S. Chevret, M. Battistella, E. M. Neidhardt, C. Nardin, F. Le Du, N. Meyer, M. Véron, L. Gambotti, A. Lamrani-Ghaouti, P. Jamme, C. Chaffaut, M. De Pontville, E. Saada-Bouzid, M. Beylot-Barry, C. Simon, T. Jouary, A. Marabelle, and L. Mortier
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Cancer Research ,Oncology ,Immunology ,Immunology and Allergy - Published
- 2023
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10. 'I Was Nothing but a Bare Skeleton Walking the Path'
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SABINE N. MEYER
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- 2023
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11. Experiment aversion among clinicians and the public — an obstacle to evidence-based medicine and public health
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Randi L. Vogt, Patrick R. Heck, Rebecca M. Mestechkin, Pedram Heydari, Christopher F. Chabris, and Michelle N. Meyer
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BackgroundRandomized controlled trials (RCTs) are essential for determining the safety and efficacy of healthcare interventions. However, both laypeople and clinicians often demonstrate experiment aversion: preferring to implement either of two interventions for everyone rather than comparing them to determine which is best. We studied whether clinician and layperson views of pragmatic RCTs for Covid-19 or other interventions became more positive early in the pandemic, which increased both the urgency and public discussion of RCTs.MethodsWe conducted several survey studies with laypeople (totaln=2,909) and two with clinicians (n=895;n=1,254) in 2020 and 2021. Participants read vignettes in which a hypothetical decision-maker who sought to improve health could choose to implement intervention A for all, implement intervention B for all, or experimentally compare A and B and implement the superior intervention. Participants rated and ranked the appropriateness of each decision.ResultsCompared to our pre-pandemic results, we found no decrease in laypeople’s aversion to non-Covid-19 experiments involving catheterization checklists and hypertension drugs. Nor were either laypeople or clinicians less averse to Covid-19 RCTs (concerning corticosteroid drugs, vaccines, intubation checklists, proning, school reopening, and mask protocols), on average. Across all vignettes and samples, levels of experiment aversion ranged from 28% to 57%, while levels of experiment appreciation (in which the RCT is rated higher than the participant’s highest-rated intervention) ranged from only 6% to 35%.ConclusionsAdvancing evidence-based medicine through pragmatic RCTs will require anticipating and addressing experiment aversion among both patients and healthcare professionals.
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- 2023
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12. Supplementary Figure Legends, Figures S1 - S7, Tables S1 - S8 from The CREBBP Acetyltransferase Is a Haploinsufficient Tumor Suppressor in B-cell Lymphoma
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Laura Pasqualucci, Riccardo Dalla-Favera, Shafinaz Hussein, Paul K. Brindle, Katia Basso, Tongwei Mo, Stefanie N. Meyer, Romain Duval, Antony B. Holmes, Sarah Nataraj, Victoria A. Wells, Sofija Vlasevska, and Jiyuan Zhang
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Supplementary Figure S1. CREBBP binds to GC-specific super-enhancers. Supplementary Figure S2. Crebbp and EP300 expression in the B cell subsets development in Crebbpfl/flCγ1-Cre and Crebbpfl/flCD19-Cre mice. Supplementary Figure S3. GSEA analysis of Crebbpfl/fl vs Crebbp+/+ Cγ1-Cre GC B cells. Supplementary Figure S4. Analysis of GC B cell responses in the Cγ1-Cre and CD19-Cre cohorts. Supplementary Figure S5. Analysis of plasma cell differentiation in the Cγ1-Cre and CD19-Cre cohorts. Supplementary Figure S6. Distribution pattern of CREBBP mutations in FL and de novo DLBCL. Supplementary Figure S7. Analysis of Crebbp-conditional knockout cohorts. Supplementary Table S1. Overlap between CREBBP bound regions and predicted superenhancers in GC B cells. Supplementary Table S2. Genes differentially expressed in Crebbpfl/fl vs Crebbp+/+ GC B cells. Supplementary Table S3. List of CREBBP "core target" genes (bound by CREBBP in human GC B cells and downregulated in Crebbpfl/flCγ1-Cre GC B cells). Supplementary Table S4. Pathway enrichment analysis of CREBBP "core target" genes (bound by CREBBP in human GC B cells and downregulated in Cγ1-Cre Crebbpfl/fl GC B cells). Supplementary Table S5. Leading edge associated with GSEA of CREBBP core target genes in the rank of genes differentially expressed in DZ vs LZ GC B cells. Supplementary Table S6. Pathway enrichment analysis of genes co-bound by CREBBP and BCL6 in human GC B cells. Supplementary Table S7. V gene rearrangement analysis of B-cell lymphomas in the Crebbpfl/f/Cγ1-Cre /VavP-Bcl2 conditional knock-out mouse model. Supplementary Table S8. List of antibodies used in FACS analysis.
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- 2023
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13. Supplementary Figure Legends, Figures S1 - S7, Tables S1 - S8 from The CREBBP Acetyltransferase Is a Haploinsufficient Tumor Suppressor in B-cell Lymphoma
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Laura Pasqualucci, Riccardo Dalla-Favera, Shafinaz Hussein, Paul K. Brindle, Katia Basso, Tongwei Mo, Stefanie N. Meyer, Romain Duval, Antony B. Holmes, Sarah Nataraj, Victoria A. Wells, Sofija Vlasevska, and Jiyuan Zhang
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Supplementary Figure S1. CREBBP binds to GC-specific super-enhancers. Supplementary Figure S2. Crebbp and EP300 expression in the B cell subsets development in Crebbpfl/flCγ1-Cre and Crebbpfl/flCD19-Cre mice. Supplementary Figure S3. GSEA analysis of Crebbpfl/fl vs Crebbp+/+ Cγ1-Cre GC B cells. Supplementary Figure S4. Analysis of GC B cell responses in the Cγ1-Cre and CD19-Cre cohorts. Supplementary Figure S5. Analysis of plasma cell differentiation in the Cγ1-Cre and CD19-Cre cohorts. Supplementary Figure S6. Distribution pattern of CREBBP mutations in FL and de novo DLBCL. Supplementary Figure S7. Analysis of Crebbp-conditional knockout cohorts. Supplementary Table S1. Overlap between CREBBP bound regions and predicted superenhancers in GC B cells. Supplementary Table S2. Genes differentially expressed in Crebbpfl/fl vs Crebbp+/+ GC B cells. Supplementary Table S3. List of CREBBP "core target" genes (bound by CREBBP in human GC B cells and downregulated in Crebbpfl/flCγ1-Cre GC B cells). Supplementary Table S4. Pathway enrichment analysis of CREBBP "core target" genes (bound by CREBBP in human GC B cells and downregulated in Cγ1-Cre Crebbpfl/fl GC B cells). Supplementary Table S5. Leading edge associated with GSEA of CREBBP core target genes in the rank of genes differentially expressed in DZ vs LZ GC B cells. Supplementary Table S6. Pathway enrichment analysis of genes co-bound by CREBBP and BCL6 in human GC B cells. Supplementary Table S7. V gene rearrangement analysis of B-cell lymphomas in the Crebbpfl/f/Cγ1-Cre /VavP-Bcl2 conditional knock-out mouse model. Supplementary Table S8. List of antibodies used in FACS analysis.
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- 2023
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14. Neural correlates of p-factor in adolescence: Cognitive control with and without enhanced positive affective demands
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Anais M. Rodriguez-Thompson, Adam Bryant Miller, Mark Wade, Kristin N. Meyer, Laura Machlin, Adrienne Bonar, Kinjal K. Patel, Matteo Giletta, Paul D. Hastings, Matthew K. Nock, Karen D. Rudolph, George M. Slavich, Mitchell J. Prinstein, and Margaret A. Sheridan
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Cognitive Neuroscience ,Radiology, Nuclear Medicine and imaging ,Neurology (clinical) ,Biological Psychiatry - Published
- 2023
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15. Proteomic analysis reveals dual requirement for Grb2 and PLCγ1 interactions for BCR-FGFR1-Driven 8p11 cell proliferation
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Malalage N. Peiris, April N. Meyer, Dalida Warda, Alexandre Rosa Campos, and Daniel J. Donoghue
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Proteomics ,Myeloproliferative Disorders ,Lymphoma ,Oncology and Carcinogenesis ,phosphoproteome ,Hematology ,Translocation, Genetic ,chromosomal translocation ,Pyrimidines ,Rare Diseases ,Oncology ,oncogenic fusion protein ,Humans ,Pyrazoles ,2.1 Biological and endogenous factors ,Pyrroles ,Receptor, Fibroblast Growth Factor, Type 1 ,Ubiquitin-Specific Proteases ,stem cell leukemia/lymphoma ,protein interactome ,Cell Proliferation ,Chromosomes, Human, Pair 8 ,GRB2 Adaptor Protein ,Biotechnology ,Cancer - Abstract
Translocation of Fibroblast Growth Factor Receptors (FGFRs) often leads to aberrant cell proliferation and cancer. The BCR-FGFR1 fusion protein, created by chromosomal translocation t(8;22)(p11;q11), contains Breakpoint Cluster Region (BCR) joined to Fibroblast Growth Factor Receptor 1 (FGFR1). BCR-FGFR1 represents a significant driver of 8p11 myeloproliferative syndrome, or stem cell leukemia/lymphoma, which progresses to acute myeloid leukemia or T-cell lymphoblastic leukemia/lymphoma. Mutations were introduced at Y177F, the binding site for adapter protein Grb2 within BCR; and at Y766F, the binding site for the membrane associated enzyme PLCγ1 within FGFR1. We examined anchorage-independent cell growth, overall cell proliferation using hematopoietic cells, and activation of downstream signaling pathways. BCR-FGFR1-induced changes in protein phosphorylation, binding partners, and signaling pathways were dissected using quantitative proteomics to interrogate the protein interactome, the phosphoproteome, and the interactome of BCR-FGFR1. The effects on BCR-FGFR1-stimulated cell proliferation were examined using the PLCγ1 inhibitor U73122, and the irreversible FGFR inhibitor futibatinib (TAS-120), both of which demonstrated efficacy. An absolute requirement is demonstrated for the dual binding partners Grb2 and PLCγ1 in BCR-FGFR1-driven cell proliferation, and new proteins such as ECSIT, USP15, GPR89, GAB1, and PTPN11 are identified as key effectors for hematopoietic transformation by BCR-FGFR1.
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- 2022
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16. Occupancy models reveal potential of conservation prioritization for Central American jaguars
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A P Calderón, J Louvrier, A Planillo, D Araya‐Gamboa, S Arroyo‐Arce, M Barrantes‐Núñez, J Carazo‐Salazar, D Corrales‐Gutiérrez, C P Doncaster, R Foster, M J García, R Garcia‐Anleu, B Harmsen, S Hernández‐Potosme, R Leonardo, D M Trigueros, R McNab, N Meyer, R Moreno, R Salom‐Pérez, A Sauma Rossi, I Thomson, D Thornton, Y Urbina, V Grimm, and S Kramer‐Schadt
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habitat suitability ,Ecology ,Nature and Landscape Conservation ,large carnivores ,jaguar conservation units ,camera‐traps ,carnivore conservation ,occupancy models ,species distribution models ,577 Ökologie ,human influence - Abstract
Understanding species-environment relationships at large spatial scales is required for the prioritization of conservation areas and the preservation of landscape connectivity for large carnivores. This endeavour is challenging for jaguars (Panthera onca), given their elusiveness, and the local nature of most jaguar studies, precluding extrapolation to larger areas. We developed an occupancy model using occurrence data of jaguars across five countries of Central America, collected from camera-trap studies of 2–12 months' duration, deployed over an area of 14 112 km 2 from 2005 to 2018. Our occupancy model showed that habitat use of jaguars increased with primary net productivity and distance to human settlements, and distance to rivers. Detection of the species was related to survey effort and research team identity. Within the jaguar extent of occurrence, 73% was deemed suitable for the species, with 47% of it lying within Jaguar Conservation Units (JCU) and 59% of JCU land being legally protected. Suitable areas were divided into four distinct clusters of continuous habitat shared across country borders. However, large areas of predicted low habitat suitability may constrict connectivity in the region. The reliability of these spatial predictions is indicated by the model validation using an independent dataset (AUC = 0.82; sensitivity = 0.766, specificity = 0.761), and concordance of our results with other studies conducted in the region. Across Central America, we found that human influence has the strongest impact on jaguar habitat use and JCUs are the main reservoirs of habitat. Therefore, conservation actions must focus on preventing habitat loss and mitigating human pressure, particularly within the clusters of continuous areas of high suitability, and on restoring habitat to foster connectivity. The long-term persistence of jaguars in the region will depend on strong international cooperation that secures jaguar populations and their habitat across Central American borders.
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- 2022
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17. Developmental nicotine exposure and masculinization of the rat preoptic area
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Rashmi Joglekar, Marty Cauley, Taylor Lipsich, David L. Corcoran, Heather B. Patisaul, Edward D. Levin, Joel N. Meyer, Margaret M. McCarthy, and Susan K. Murphy
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Male ,Nicotine ,Sex Characteristics ,Sex Differentiation ,General Neuroscience ,Animals ,Female ,Testosterone ,Electronic Nicotine Delivery Systems ,Toxicology ,Preoptic Area ,Article ,Rats - Abstract
Nicotine is a neuroteratogenic component of tobacco smoke, e-cigarettes, and other products and can exert sex-specific effects in the developing brain, likely mediated through sex hormones. Estradiol modulates expression of nicotinic acetylcholine receptors in rats, and plays critical roles in neurodevelopmental processes, including sexual differentiation of the brain. Here, we examined the effects of developmental nicotine exposure on the sexual differentiation of the preoptic area (POA), a brain region that normally displays robust structural sexual dimorphisms and controls adult mating behavior in rodents. Using a rat model of gestational exposure, developing pups were exposed to nicotine (2 mg/kg/day) via maternal osmotic minipump (subcutaneously, sc) throughout the critical window for brain sexual differentiation. At postnatal day (PND) 4, a subset of offspring was analyzed for epigenetic effects in the POA. At PND40, all offspring were gonadectomized, implanted with a testosterone-releasing capsule (sc), and assessed for male sexual behavior at PND60. Following sexual behavior assessment, the area of the sexually dimorphic nucleus of the POA (SDN-POA) was measured using immunofluorescent staining techniques. In adults, normal sex differences in male sexual behavior and in the SDN-POA area were eliminated in nicotine-treated animals. Using novel analytical approaches to evaluate overall masculinization of the adult POA, we identified significant masculinization of the nicotine-treated female POA. In neonates (PND4), nicotine exposure induced trending alterations in methylation-dependent masculinizing gene expression and DNA methylation levels at sexually-dimorphic differentially methylated regions, suggesting that developmental nicotine exposure is capable of triggering masculinization of the rat POA via epigenetic mechanisms.
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- 2022
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18. Mental Health Surveillance Among Children — United States, 2013–2019
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Rebecca H, Bitsko, Angelika H, Claussen, Jesse, Lichstein, Lindsey I, Black, Sherry Everett, Jones, Melissa L, Danielson, Jennifer M, Hoenig, Shane P, Davis Jack, Debra J, Brody, Shiromani, Gyawali, Matthew J, Maenner, Margaret, Warner, Kristin M, Holland, Ruth, Perou, Alex E, Crosby, Stephen J, Blumberg, Shelli, Avenevoli, Jennifer W, Kaminski, Reem M, Ghandour, and Leah N, Meyer
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Adult ,Depressive Disorder, Major ,Young Adult ,Mental Health ,Adolescent ,Child, Preschool ,Chronic Disease ,Prevalence ,Humans ,Suicide, Attempted ,General Medicine ,Child ,United States - Abstract
Mental health encompasses a range of mental, emotional, social, and behavioral functioning and occurs along a continuum from good to poor. Previous research has documented that mental health among children and adolescents is associated with immediate and long-term physical health and chronic disease, health risk behaviors, social relationships, education, and employment. Public health surveillance of children's mental health can be used to monitor trends in prevalence across populations, increase knowledge about demographic and geographic differences, and support decision-making about prevention and intervention. Numerous federal data systems collect data on various indicators of children's mental health, particularly mental disorders. The 2013-2019 data from these data systems show that mental disorders begin in early childhood and affect children with a range of sociodemographic characteristics. During this period, the most prevalent disorders diagnosed among U.S. children and adolescents aged 3-17 years were attention-deficit/hyperactivity disorder and anxiety, each affecting approximately one in 11 (9.4%-9.8%) children. Among children and adolescents aged 12-17 years, one fifth (20.9%) had ever experienced a major depressive episode. Among high school students in 2019, 36.7% reported persistently feeling sad or hopeless in the past year, and 18.8% had seriously considered attempting suicide. Approximately seven in 100,000 persons aged 10-19 years died by suicide in 2018 and 2019. Among children and adolescents aged 3-17 years, 9.6%-10.1% had received mental health services, and 7.8% of all children and adolescents aged 3-17 years had taken medication for mental health problems during the past year, based on parent report. Approximately one in four children and adolescents aged 12-17 years reported having received mental health services during the past year. In federal data systems, data on positive indicators of mental health (e.g., resilience) are limited. Although no comprehensive surveillance system for children's mental health exists and no single indicator can be used to define the mental health of children or to identify the overall number of children with mental disorders, these data confirm that mental disorders among children continue to be a substantial public health concern. These findings can be used by public health professionals, health care providers, state health officials, policymakers, and educators to understand the prevalence of specific mental disorders and other indicators of mental health and the challenges related to mental health surveillance.
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- 2022
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19. Detecting Developers’ Task Switches and Types
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Thomas Zimmermann, Katja Kevic, Gail C. Murphy, Chris Satterfield, Manuela Züger, Thomas Fritz, André N. Meyer, and University of Zurich
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Experience sampling method ,10009 Department of Informatics ,Computer science ,Context (computing) ,020207 software engineering ,Cognition ,02 engineering and technology ,000 Computer science, knowledge & systems ,Field (computer science) ,Variety (cybernetics) ,Task (project management) ,Reduction (complexity) ,Human–computer interaction ,0202 electrical engineering, electronic engineering, information engineering ,Software ,Scope (computer science) - Abstract
Developers work on a broad variety of tasks during their workdays and constantly switch between them. While these task switches can be beneficial, they can also incur a high cognitive burden on developers, since they have to continuously remember and rebuild task context - the artifacts and applications relevant to the task. Researchers have therefore proposed to capture task context more explicitly and use it to provide better task support, such as task switch reduction or task resumption support. Yet, these approaches generally require the developer to manually identify task switches. Automatic approaches for predicting task switches have so far been limited in their accuracy, scope, evaluation, and the time discrepancy between predicted and actual task switches. In our work, we examine the use of automatically collected computer interaction data for detecting developers' task switches as well as task types. In two field studies - a 4h observational study and a multi-day study with experience sampling - we collected data from a total of 25 professional developers. Our study results show that we are able to use temporal and semantic features from developers' computer interaction data to detect task switches and types in the field with high accuracy of 84% and 61% respectively, and within a short time window of less than 1.6 minutes on average from the actual task switch. We discuss our findings and their practical value for a wide range of applications in real work settings.
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- 2022
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20. CCR Translation for This Article from BCL2 Predicts Survival in Germinal Center B-cell–like Diffuse Large B-cell Lymphoma Treated with CHOP-like Therapy and Rituximab
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Wing C. Chan, Dennis D. Weisenburger, James O. Armitage, Randy D. Gascoyne, Raymond R. Tubbs, James R. Cook, Rita M. Braziel, Elias Campo, Jan Delabie, German Ott, Andreas Rosenwald, Elaine Jaffe, Lisa Rimsza, Louis M. Staudt, Joseph M. Connors, Timothy C. Greiner, Julie M. Vose, Nathalie A. Johnson, Lynette M. Smith, Paul N. Meyer, and Javeed Iqbal
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CCR Translation for This Article from BCL2 Predicts Survival in Germinal Center B-cell–like Diffuse Large B-cell Lymphoma Treated with CHOP-like Therapy and Rituximab
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- 2023
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21. Supplementary Figure Legends 1-3, Tables 1-3 from BCL2 Predicts Survival in Germinal Center B-cell–like Diffuse Large B-cell Lymphoma Treated with CHOP-like Therapy and Rituximab
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Wing C. Chan, Dennis D. Weisenburger, James O. Armitage, Randy D. Gascoyne, Raymond R. Tubbs, James R. Cook, Rita M. Braziel, Elias Campo, Jan Delabie, German Ott, Andreas Rosenwald, Elaine Jaffe, Lisa Rimsza, Louis M. Staudt, Joseph M. Connors, Timothy C. Greiner, Julie M. Vose, Nathalie A. Johnson, Lynette M. Smith, Paul N. Meyer, and Javeed Iqbal
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PDF file - 134K
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- 2023
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22. Data from BCL2 Predicts Survival in Germinal Center B-cell–like Diffuse Large B-cell Lymphoma Treated with CHOP-like Therapy and Rituximab
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Wing C. Chan, Dennis D. Weisenburger, James O. Armitage, Randy D. Gascoyne, Raymond R. Tubbs, James R. Cook, Rita M. Braziel, Elias Campo, Jan Delabie, German Ott, Andreas Rosenwald, Elaine Jaffe, Lisa Rimsza, Louis M. Staudt, Joseph M. Connors, Timothy C. Greiner, Julie M. Vose, Nathalie A. Johnson, Lynette M. Smith, Paul N. Meyer, and Javeed Iqbal
- Abstract
Purpose: We have previously shown the prognostic significance of BCL2 expression in the activated B-cell–like diffuse large B-cell lymphoma (ABC-DLBCL) patients treated with cyclophosphamide-Adriamycin-vincristine-prednisone (CHOP) or CHOP-like therapy. However, after the inclusion of rituximab (R) in the CHOP regimen, several conflicting observations about the prognostic value of BCL2 expression have been reported.Experimental Design: We evaluated the R-CHOP cohort of 221 DLBCL cases with gene expression profiling data. BCL2 protein (n = 169), mRNA (n = 221) expression, and t(14;18) (n = 144) were correlated with clinical outcome. The CHOP cohort (n = 181) was used for comparative analysis.Results: BCL2 protein expression has significant impact on overall survival (OS) and event-free survival (EFS) in DLBCL (OS, P = 0.009; EFS, P = 0.001) and GCB-DLBCL (OS, P = 0.03; EFS, P = 0.002) but not in ABC-DLBCL in the R-CHOP cohort. The survival differences for EFS in GCB-DLBCL were still observed in multivariate analysis. At the mRNA level, this correlation was observed in EFS in DLBCL (P = 0.006), but only a trend was observed in GCB-DLBCL (P = 0.09). The t(14;18) was detected in 34% of GCB-DLBCL but was not associated with significant differences in survival. Gene enrichment analysis identified significant enrichment of the DLBCL “stromal-1” signatures and hypoxia-inducible factor 1 (HIF1-α) signature in BCL2(−)GCB-DLBCL, whereas TFH cell signatures were enriched in BCL2(+)GCB-DLBCL.Conclusion: The prognostic significance of BCL2 has changed after inclusion of rituximab in the treatment protocol and is observed in the GCB-DLBCL rather than the ABC-DLBCL. Although rituximab has benefited patients in both DLBCL subgroups, the BCL2(+)GCB-DLBCL seems to receive less benefit from this treatment and may require other novel therapeutic intervention. Clin Cancer Res; 17(24); 7785–95. ©2011 AACR.
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- 2023
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23. Supplementary Figures 1-3 from BCL2 Predicts Survival in Germinal Center B-cell–like Diffuse Large B-cell Lymphoma Treated with CHOP-like Therapy and Rituximab
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Wing C. Chan, Dennis D. Weisenburger, James O. Armitage, Randy D. Gascoyne, Raymond R. Tubbs, James R. Cook, Rita M. Braziel, Elias Campo, Jan Delabie, German Ott, Andreas Rosenwald, Elaine Jaffe, Lisa Rimsza, Louis M. Staudt, Joseph M. Connors, Timothy C. Greiner, Julie M. Vose, Nathalie A. Johnson, Lynette M. Smith, Paul N. Meyer, and Javeed Iqbal
- Abstract
PDF file - 106K
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- 2023
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24. Wrestling with Social and Behavioral Genomics: Risks, Potential Benefits, and Ethical Responsibility
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Michelle N. Meyer, Paul S. Appelbaum, Daniel J. Benjamin, Shawneequa L. Callier, Nathaniel Comfort, Dalton Conley, Jeremy Freese, Nanibaa' A. Garrison, Evelynn M. Hammonds, K. Paige Harden, Sandra Soo‐Jin Lee, Alicia R. Martin, Daphne Oluwaseun Martschenko, Benjamin M. Neale, Rohan H. C. Palmer, James Tabery, Eric Turkheimer, Patrick Turley, and Erik Parens
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Philosophy ,Issues, ethics and legal aspects ,Health (social science) ,Health Policy ,General Medicine - Published
- 2023
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25. Wrestling with Public Input on an Ethical Analysis of Scientific Research
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Daphne Oluwaseun Martschenko, Shawneequa L. Callier, Nanibaa’ A. Garrison, Sandra Soo‐Jin Lee, Patrick Turley, Michelle N. Meyer, and Erik Parens
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Philosophy ,Issues, ethics and legal aspects ,Health (social science) ,Health Policy ,General Medicine - Published
- 2023
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26. Oncogenic driver FGFR3-TACC3 requires five coiled-coil heptads for activation and disulfide bond formation for stability
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Clark G. Wang, Malalage N. Peiris, April N. Meyer, Katelyn N. Nelson, and Daniel J. Donoghue
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Oncogene Proteins ,Tumor ,Fibroblast Growth Factor ,Oncology and Carcinogenesis ,glioblastoma ,FGFR3-TACC3 ,Cell Line ,chromosomal translocation ,Rare Diseases ,Oncology ,Neoplasms ,coiled-coil ,oncogenic fusion protein ,Humans ,2.1 Biological and endogenous factors ,Aetiology ,Fusion ,Microtubule-Associated Proteins ,Type 3 ,Receptor ,Cancer ,Biotechnology - Abstract
FGFR3-TACC3 represents an oncogenic fusion protein frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Various exon breakpoints of FGFR3-TACC3 have been identified in cancers; these were analyzed to determine the minimum contribution of TACC3 for activation of the FGFR3-TACC3 fusion protein. While TACC3 exons 11 and 12 are dispensable for activity, our results show that FGFR3-TACC3 requires exons 13-16 for biological activity. A detailed analysis of exon 13, which consists of 8 heptads forming a coiled coil, further defined the minimal region for biological activity as consisting of 5 heptads from exon 13, in addition to exons 14-16. These conclusions were supported by transformation assays of biological activity, examination of MAPK pathway activation, analysis of disulfide-bonded FGFR3-TACC3, and by examination of the Endoglycosidase H-resistant portion of FGFR3-TACC3. These results demonstrate that clinically identified FGFR3-TACC3 fusion proteins differ in their biological activity, depending upon the specific breakpoint. This study further suggests the TACC3 dimerization domain of FGFR3-TACC3 as a novel target in treating FGFR translocation driven cancers.
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- 2023
27. Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps
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Ricardo A. Verdugo, Palmira Granados Moreno, Amy C. Sturm, Alicia Zhou, Masahiro Kanai, Mary K. Balaconis, Charles N. Rotimi, J. Brent Richards, Elisabeth Widen, Saskia C. Sanderson, Anna C. F. Lewis, Genevieve L. Wojcik, Cristen J. Willer, Bartha Maria Knoppers, Samuli Ripatti, Kazuto Kato, Chani J. Hodonsky, Adebowale Adeyemo, Deanna R. Darnes, Alicia R. Martin, Segun Fatumo, Yukinori Okada, Michael Inouye, Michelle N. Meyer, Lucas Richter, and Mark I. McCarthy
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business.industry ,Environmental health ,Medicine ,Polygenic risk score ,General Medicine ,business ,General Biochemistry, Genetics and Molecular Biology - Published
- 2021
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28. Risk of lead exposure from wild game consumption from cross-sectional studies in Madre de Dios, Peru
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Axel J. Berky, Emily Robie, Susy Navio Chipa, Ernesto J. Ortiz, Emma J. Palmer, Nelson A. Rivera, Ana Maria Morales Avalos, Joel N. Meyer, Heileen Hsu-Kim, and William K. Pan
- Abstract
Studies have shown elevated blood lead levels (BLL) in residents of remote communities in the Amazon, yet sources of lead exposure are not fully understood, such as lead ammunition consumed in wild game.Data was collected during two cross-sectional studies that enrolled 307 individuals in 26 communities. Regression models with community random effects were used to evaluate risk factors for BLLs, including diet, water source, smoking, sex, age, and indigenous status. The All-Ages Lead Model (AALM) from the Environmental Protection Agency (EPA) was used to estimate background and dose from wild game consumption.Indigenous status and wild game consumption were associated with increased BLLs. Indigenous participants had 2.52 μg/dL (95% CI: 1.95-3.24) higher BLLs compared to non-indigenous. Eating wild game was associated with a 1.41 μg/dL (95% CI: 1.20-1.70) increase in BLLs. Two or more portions per serving were associated with increased BLLs of 1.66 μg/dL (95% CI: 1.10-2.57), compared to smaller servings. Using the AALM, we estimate background lead exposures to be 20 μg/day with consumption of wild game contributing 500 μg/meal. Lastly, we found a strong association between BLLs and mercury exposure.Consumption of wild game hunted with lead ammunition may pose a common source of lead exposure in the Amazon. Communities that rely on wild game and wild fish may face a dual burden of exposure to lead and mercury, respectively.
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- 2022
29. A Randomized Trial of Behavioral Nudges Delivered Through Text Messages to Increase Influenza Vaccination Among Patients With an Upcoming Primary Care Visit
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Mitesh S. Patel, Katherine L. Milkman, Linnea Gandhi, Heather N. Graci, Dena Gromet, Hung Ho, Joseph S. Kay, Timothy W. Lee, Jake Rothschild, Modupe Akinola, John Beshears, Jonathan E. Bogard, Alison Buttenheim, Christopher Chabris, Gretchen B. Chapman, James J. Choi, Hengchen Dai, Craig R. Fox, Amir Goren, Matthew D. Hilchey, Jillian Hmurovic, Leslie K. John, Dean Karlan, Melanie Kim, David Laibson, Cait Lamberton, Brigitte C. Madrian, Michelle N. Meyer, Maria Modanu, Jimin Nam, Todd Rogers, Renante Rondina, Silvia Saccardo, Maheen Shermohammed, Dilip Soman, Jehan Sparks, Caleb Warren, Megan Weber, Ron Berman, Chalanda N. Evans, Seung Hyeong Lee, Christopher K. Snider, Eli Tsukayama, Christophe Van den Bulte, Kevin G. Volpp, and Angela L. Duckworth
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Health (social science) ,Public Health, Environmental and Occupational Health - Abstract
Purpose To evaluate if nudges delivered by text message prior to an upcoming primary care visit can increase influenza vaccination rates. Design Randomized, controlled trial. Setting Two health systems in the Northeastern US between September 2020 and March 2021. Subjects 74,811 adults. Interventions Patients in the 19 intervention arms received 1-2 text messages in the 3 days preceding their appointment that varied in their format, interactivity, and content. Measures Influenza vaccination. Analysis Intention-to-treat. Results Participants had a mean (SD) age of 50.7 (16.2) years; 55.8% (41,771) were female, 70.6% (52,826) were White, and 19.0% (14,222) were Black. Among the interventions, 5 of 19 (26.3%) had a significantly greater vaccination rate than control. On average, the 19 interventions increased vaccination relative to control by 1.8 percentage points or 6.1% ( P = .005). The top performing text message described the vaccine to the patient as “reserved for you” and led to a 3.1 percentage point increase (95% CI, 1.3 to 4.9; P < .001) in vaccination relative to control. Three of the top five performing messages described the vaccine as “reserved for you.” None of the interventions performed worse than control. Conclusions Text messages encouraging vaccination and delivered prior to an upcoming appointment significantly increased influenza vaccination rates and could be a scalable approach to increase vaccination more broadly.
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- 2022
30. Caractéristiques cliniques et tumorales, selon le sexe, du cancer bronchique primitif (CBP) en France : Résultats de l’étude KBP 2020
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D. Templement, N. Meyer, E. Auvray, M. Sabatini, M. Fore, C. Dussopt, E. Lecuyer, W. Al Sheikh, M. Tiercin, R. Haouachi, T. Saelens, B. Martignac, J.-Y. Tavernier, C. Maurer, H. Ghalloussi-Tebai, A. Belle, C. Vincent, L. Thirard, P. Demontrond, and D. Debieuvre
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Pulmonary and Respiratory Medicine - Published
- 2023
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31. Performance of a deep convolutional neural network for MRI-based vertebral body measurements and insufficiency fracture detection
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Christoph Germann, André N. Meyer, Matthias Staib, Reto Sutter, Benjamin Fritz, University of Zurich, and Germann, Christoph
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2741 Radiology, Nuclear Medicine and Imaging ,610 Medicine & health ,10046 Balgrist University Hospital, Swiss Spinal Cord Injury Center ,Radiology, Nuclear Medicine and imaging ,10060 Epidemiology, Biostatistics and Prevention Institute (EBPI) ,General Medicine - Abstract
Objectives The aim is to validate the performance of a deep convolutional neural network (DCNN) for vertebral body measurements and insufficiency fracture detection on lumbar spine MRI. Methods This retrospective analysis included 1000 vertebral bodies in 200 patients (age 75.2 ± 9.8 years) who underwent lumbar spine MRI at multiple institutions. 160/200 patients had ≥ one vertebral body insufficiency fracture, 40/200 had no fracture. The performance of the DCNN and that of two fellowship-trained musculoskeletal radiologists in vertebral body measurements (anterior/posterior height, extent of endplate concavity, vertebral angle) and evaluation for insufficiency fractures were compared. Statistics included (a) interobserver reliability metrics using intraclass correlation coefficient (ICC), kappa statistics, and Bland-Altman analysis, and (b) diagnostic performance metrics (sensitivity, specificity, accuracy). A statistically significant difference was accepted if the 95% confidence intervals did not overlap. Results The inter-reader agreement between radiologists and the DCNN was excellent for vertebral body measurements, with ICC values of > 0.94 for anterior and posterior vertebral height and vertebral angle, and good to excellent for superior and inferior endplate concavity with ICC values of 0.79–0.85. The performance of the DCNN in fracture detection yielded a sensitivity of 0.941 (0.903–0.968), specificity of 0.969 (0.954–0.980), and accuracy of 0.962 (0.948–0.973). The diagnostic performance of the DCNN was independent of the radiological institution (accuracy 0.964 vs. 0.960), type of MRI scanner (accuracy 0.957 vs. 0.964), and magnetic field strength (accuracy 0.966 vs. 0.957). Conclusions A DCNN can achieve high diagnostic performance in vertebral body measurements and insufficiency fracture detection on heterogeneous lumbar spine MRI. Key Points • A DCNN has the potential for high diagnostic performance in measuring vertebral bodies and detecting insufficiency fractures of the lumbar spine.
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- 2022
32. Resistance of mitochondrial DNA to cadmium and Aflatoxin B1 damage-induced germline mutation accumulation in C. elegans
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Tess C Leuthner, Laura Benzing, Brendan F Kohrn, Christina M Bergemann, Michael J Hipp, Kathleen A Hershberger, Danielle F Mello, Tymofii Sokolskyi, Kevin Stevenson, Ilaria R Merutka, Sarah A Seay, Simon G Gregory, Scott R Kennedy, and Joel N Meyer
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Mutation Accumulation ,Aflatoxin B1 ,Germ Cells ,Mutation ,Genetics ,Animals ,Caenorhabditis elegans ,DNA, Mitochondrial ,Cadmium ,Mitochondria - Abstract
Mitochondrial DNA (mtDNA) is prone to mutation in aging and over evolutionary time, yet the processes that regulate the accumulation of de novo mtDNA mutations and modulate mtDNA heteroplasmy are not fully elucidated. Mitochondria lack certain DNA repair processes, which could contribute to polymerase error-induced mutations and increase susceptibility to chemical-induced mtDNA mutagenesis. We conducted error-corrected, ultra-sensitive Duplex Sequencing to investigate the effects of two known nuclear genome mutagens, cadmium and Aflatoxin B1, on germline mtDNA mutagenesis in Caenorhabditis elegans. Detection of thousands of mtDNA mutations revealed pervasive heteroplasmy in C. elegans and that mtDNA mutagenesis is dominated by C:G → A:T mutations generally attributed to oxidative damage. However, there was no effect of either exposure on mtDNA mutation frequency, spectrum, or trinucleotide context signature despite a significant increase in nuclear mutation rate after aflatoxin B1 exposure. Mitophagy-deficient mutants pink-1 and dct-1 accumulated significantly higher levels of mtDNA damage compared to wild-type C. elegans after exposures. However, there were only small differences in mtDNA mutation frequency, spectrum, or trinucleotide context signature compared to wild-type after 3050 generations, across all treatments. These findings suggest mitochondria harbor additional previously uncharacterized mechanisms that regulate mtDNA mutational processes across generations.
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- 2022
33. Exploring access to genomic risk information and the contours of the HIPAA public health exception
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Jennifer K Wagner, Juhi K Tanniru, Courtney A Chane, and Michelle N Meyer
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Medicine (miscellaneous) ,Law ,Biochemistry, Genetics and Molecular Biology (miscellaneous) - Abstract
Considerable resources have been invested in research to identify pathogenic and likely pathogenic variants that cause morbidity and mortality and also in returning these results to patients. The public health impact and cost-effectiveness of these efforts are maximized when probands’ relatives are informed of their risk and offered testing. However, such ‘Traceback’ cascade testing programs face multiple obstacles, including perceived or actual legal and regulatory hurdles. Here, using genetic cancer syndromes as a test case, we explore the contours of the Public Health Exception to the HIPAA Privacy Rule to assess whether it is a viable pathway for implementing a Traceback program. After examining the Privacy Rule as well as state laws and regulations for reportable conditions and genetic privacy, we conclude that this is not currently a viable approach for Traceback programs. We conclude by reflecting on ethical considerations of leveraging HIPAA’s public health exception to disclose PHI directly to at-risk relatives and offering insights for how legal hurdles to such a Traceback program could be overcome, if desired.
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- 2022
34. Epigenetic biomarkers of autoimmune risk and protective antioxidant signaling in methylmercury-exposed adults
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Caren Weinhouse, Luiza Perez, Ian Ryde, Jaclyn M. Goodrich, J. Jaime Miranda, Heileen Hsu-Kim, Susan K. Murphy, Joel N. Meyer, and William K. Pan
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I.AbstractBackgroundMethylmercury (MeHg) is an environmental pollutant of global public health concern. MeHg is associated with immune dysfunction but the underlying mechanisms are unclear. The most common route of MeHg exposure is through consumption of fatty fish that contain beneficial n-3 polyunsaturated fatty acids (PUFA) that may protect against MeHg toxicity.ObjectivesTo better inform individual costs and benefits of fish consumption, we aimed to identify candidate epigenetic biomarkers of biological responses that reflect MeHg toxicity and PUFA protection.MethodsWe profiled genome-wide DNA methylation using Illumina Infinium MethylationEPIC BeadChip in whole blood from N=32 individuals from Madre de Dios, Peru. Madre de Dios has high artisanal and small-scale gold mining activity, which results in high MeHg exposure to nearby residents. We compared DNA methylation in N=16 individuals with high (>10 µg/g) vs. N=16 individuals with low (ResultsWe identified hypomethylated (i.e., likely activated) genes and promoters in high vs. low MeHg-exposed participants linked to Th1/Th2 immune imbalance, decreased IL-7 signaling, and increased marginal zone B cells. These three pathways are feasible mechanisms for MeHg-induced autoimmunity. In addition, we identified candidate epigenetic biomarkers of PUFA-mediated protection: hypomethylated enhancer binding sites for retinoid X receptor (RXR) and retinoic acid receptor α (RARα). Last, we observed hypomethylated enhancer and promoter binding sites for glucocorticoid receptor (GR), which is associated with developmental neurotoxicity, and transcription factor 7-like 2 (TCF7L2), which is associated with type 2 diabetes (T2D) risk.DiscussionHere, we identify a set of candidate epigenetic biomarkers for assessing individualized risk of autoimmune response and protection against neurotoxicity due to MeHg exposure and fish consumption. In addition, our results may inform surrogate tissue biomarkers of early MeHg exposure-related neurotoxicity and T2D risk.
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- 2022
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35. Total electron temperature derived from quasi-thermal noise spectroscopy in the pristine solar wind from Parker Solar Probe observations
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M. Liu, K. Issautier, M. Moncuquet, N. Meyer-Vernet, M. Maksimovic, J. Huang, M. M. Martinovic, L. Griton, N. Chrysaphi, V. K. Jagarlamudi, S. D. Bale, M. Pulupa, J. C. Kasper, and M. L. Stevens
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Astrophysics - Solar and Stellar Astrophysics ,Physics - Space Physics ,Space and Planetary Science ,FOS: Physical sciences ,Astronomy and Astrophysics ,Solar and Stellar Astrophysics (astro-ph.SR) ,Space Physics (physics.space-ph) - Abstract
The Quasi-thermal noise (QTN) technique is a reliable tool to yield accurate measurements of the electron parameters in the solar wind. We apply this method on Parker Solar Probe (PSP) observations to derive the total electron temperature ($T_e$) from the linear fit of the high-frequency part of the QTN spectra acquired by the RFS/FIELDS instrument, and present a combination of 12-day period of observations around each perihelion from Encounter One (E01) to Ten (E10) (with E08 not included) with the heliocentric distance varying from about 13 to 60 solar radii ($R_\odot{}$). We find that the total electron temperature decreases with the distance as $\sim$$R^{-0.66}$, which is much slower than adiabatic. The extrapolated $T_e$ based on PSP observations is consistent with the exospheric solar wind model prediction at $\sim$10 $R_\odot{}$, Helios observations at $\sim$0.3 AU and Wind observations at 1 AU. Also, $T_e$, extrapolated back to 10 $R_\odot{}$, is almost the same as the strahl electron temperature $T_s$ (measured by SPAN-E) which is considered to be closely related to or even almost equal to the coronal electron temperature. Furthermore, the radial $T_e$ profiles in the slower solar wind (or flux tube with larger mass flux) are steeper than those in the faster solar wind (or flux tube with smaller mass flux). More pronounced anticorrelated $V_p$-$T_e$ is observed when the solar wind is slower and closer to the Sun., Comment: 10 pages, 7 figures, and Astronomy & Astrophysics Accepted
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- 2023
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36. Diagnosis and staging of lung cancer with the use of one single echoendoscope in both the trachea and the esophagus: A practical guide
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Lars Konge, Sara Colella, Paul Frost Clementsen, Goran Nadir Salih, Christian Jenssen, Christian N Meyer, Shailesh Kolekar, Uffe Bodtger, Christoph F. Dietrich, Rafi Nessar, Ida Skovgaard Christiansen, Michael Hocke, and Felix J.F. Herth
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medicine.medical_specialty ,Staging ,diagnosis ,Mediastinoscopy ,Diagnosis ,medicine ,Fluoroscopy ,Radiology, Nuclear Medicine and imaging ,Esophagus ,Lung cancer ,Hepatology ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Magnetic resonance imaging ,staging ,medicine.disease ,Lung ultrasound ,respiratory tract diseases ,Training Course ,Echoendoscope ,medicine.anatomical_structure ,echoendoscope ,Positron emission tomography ,Radiology ,Tomography ,business - Abstract
Accurate staging of non-small cell lung cancer (NSCLC) is crucial for allocation to surgical, medical or multimodal treatment. EUS and endobronchial ultrasound (EBUS) have gained ground in the diagnosis and staging of lung cancer in addition to radiological imaging (e.g., computed tomography, fluoroscopy, and magnetic resonance imaging), nuclear medicine techniques (e.g. positron emission tomography, PET), combined techniques (e.g., fluorodesoxyglucosepositron emission tomography scanning), and sonographic imaging including conventional transcutaneous mediastinal and lung ultrasound. By using one single echoendoscope in both the trachea and the esophagus, surgical staging procedures (e.g. mediastinoscopy and video assisted thoracoscopy) can be avoided in a considerable proportion of patients with NSCLC.
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- 2021
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37. Xenobiotic metabolism and transport in Caenorhabditis elegans
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Samuel J. Widmayer, Laura E. Jameson, Stefan Taubert, Riccardo F. Romersi, Joel N. Meyer, Jessica H. Hartman, Christina M. Bergemann, Maxwell C.K. Leung, Dillon E. King, Erik C. Andersen, and Katherine S. Morton
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0303 health sciences ,Toxicodynamics ,biology ,Drug discovery ,Health, Toxicology and Mutagenesis ,Context (language use) ,Xenobiotic transport ,Computational biology ,010501 environmental sciences ,Toxicology ,biology.organism_classification ,01 natural sciences ,3. Good health ,03 medical and health sciences ,chemistry.chemical_compound ,chemistry ,Toxicokinetics ,Microbiome ,Xenobiotic ,Caenorhabditis elegans ,030304 developmental biology ,0105 earth and related environmental sciences - Abstract
Caenorhabditis elegans has emerged as a major model in biomedical and environmental toxicology. Numerous papers on toxicology and pharmacology in C. elegans have been published, and this species has now been adopted by investigators in academic toxicology, pharmacology, and drug discovery labs. C. elegans has also attracted the interest of governmental regulatory agencies charged with evaluating the safety of chemicals. However, a major, fundamental aspect of toxicological science remains underdeveloped in C. elegans: xenobiotic metabolism and transport processes that are critical to understanding toxicokinetics and toxicodynamics, and extrapolation to other species. The aim of this review was to initially briefly describe the history and trajectory of the use of C. elegans in toxicological and pharmacological studies. Subsequently, physical barriers to chemical uptake and the role of the worm microbiome in xenobiotic transformation were described. Then a review of what is and is not known regarding the classic Phase I, Phase II, and Phase III processes was performed. In addition, the following were discussed (1) regulation of xenobiotic metabolism; (2) review of published toxicokinetics for specific chemicals; and (3) genetic diversity of these processes in C. elegans. Finally, worm xenobiotic transport and metabolism was placed in an evolutionary context; key areas for future research highlighted; and implications for extrapolating C. elegans toxicity results to other species discussed.
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- 2021
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38. An ethics framework for consolidating and prioritizing COVID-19 clinical trials
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Steven Joffe, Sara Chandros Hull, Seema Mohapatra, Holly Fernandez Lynch, Michelle N. Meyer, Kayte Spector-Bagdady, Jeremy Sugarman, Luke Gelinas, Barbara E. Bierer, Richard R. Sharp, David Magnus, and Benjamin S. Wilfond
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Biomedical Research ,Process (engineering) ,media_common.quotation_subject ,Psychological intervention ,Diversification (marketing strategy) ,0603 philosophy, ethics and religion ,Ethics, Research ,Scarcity ,03 medical and health sciences ,0302 clinical medicine ,Consolidation (business) ,Humans ,030212 general & internal medicine ,media_common ,Pharmacology ,Upstream (petroleum industry) ,Clinical Trials as Topic ,Health Priorities ,SARS-CoV-2 ,COVID-19 ,06 humanities and the arts ,General Medicine ,Clinical trial ,Risk analysis (engineering) ,Research Design ,Health Resources ,Portfolio ,060301 applied ethics ,Business ,Ethics Committees, Research - Abstract
Given the dearth of established safe and effective interventions to respond to COVID-19, there is an urgent ethical imperative to conduct meaningful clinical research. The good news is that interventions to be tested are not in short supply. Unfortunately, the human and material resources needed to conduct these trials are finite. It is essential that trials be robust and meet enrollment targets and that lower-quality studies not be permitted to displace higher-quality studies, delaying answers to critical questions. Yet, with few exceptions, existing research review bodies and processes are not designed to ensure these conditions are satisfied. To meet this challenge, we offer guidance for research institutions about how to ethically consolidate and prioritize COVID-19 clinical trials, while recognizing that consolidation and prioritization should also take place upstream (among manufacturers and funders) and at a higher level (e.g. nationally). In our proposed three-stage process, trials must first meet threshold criteria. Those that do are evaluated in a second stage to determine whether the institution has sufficient capacity to support all proposed trials. If it does not, the third stage entails evaluating studies against two additional sets of comparative prioritization criteria: those specific to the study and those that aim to advance diversification of an institution’s research portfolio. To implement these criteria fairly, we propose that research institutions form COVID-19 research prioritization committees. We briefly discuss some important attributes of these committees, drawing on the authors’ experiences at our respective institutions. Although we focus on clinical trials of COVID-19 therapeutics, our guidance should prove useful for other kinds of COVID-19 research, as well as non-pandemic research, which can raise similar challenges due to the scarcity of research resources.
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- 2021
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39. Transculturality and Filmic Practice. Cultural Difference and Transcultural Belonging in ‘Babel’
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Sabine N. Meyer
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- 2021
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40. Efficacité du cémiplimab dans le carcinome épidermoïde cutané évolué chez les patients atteints de leucémie lymphoïde chronique
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J. De Quatrebarbes, F. Aubin, F. Grange, B. Dreno, M. Boubaya, E. Archier, J.P. Arnault, N. Beneton, F. Brunet Possenti, P. Guillet, C. Lesage, S. Mansard, A.B. Duval-Modeste, N. Meyer, N. Poulalhon, E.M. Neidhardt, S. Dalac, L. Mortier, and E. Maubec
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Ocean Engineering ,Safety, Risk, Reliability and Quality - Published
- 2022
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41. L’efficacité de l’immunothérapie dans le mélanome choroïdien en fonction du patron métastatique
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J. Ramspacher, L. Chaltiel, V. Sibaud, C. Pages, S. Boulinguez, and N. Meyer
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Ocean Engineering ,Safety, Risk, Reliability and Quality - Published
- 2022
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42. Multi- and Transgenerational Effects of Developmental Exposure to Environmental Levels of PFAS and PFAS Mixture in Zebrafish (Danio rerio)
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Alex Haimbaugh, Chia-Chen Wu, Camille Akemann, Danielle N. Meyer, Mackenzie Connell, Mohammad Abdi, Aicha Khalaf, Destiny Johnson, and Tracie R. Baker
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Chemical Health and Safety ,PFAS ,PFAS mixtures ,epigenetics ,zebrafish ,transgenerational ,Health, Toxicology and Mutagenesis ,Toxicology - Abstract
Per- and polyfluoroalkyl substances (PFASs) are ubiquitous in the environment and are tied to myriad health effects. Despite the phasing out of the manufacturing of two types of PFASs (perfluorosulfonic acid (PFOS) and perfluorooctanoic acid (PFOA)), chemical composition renders them effectively indestructible by ambient environmental processes, where they thus remain in water. Exposure via water can affect both human and aquatic wildlife. PFASs easily cross the placenta, exposing the fetus at critical windows of development. Little is known about the effects of low-level exposure during this period; even less is known about the potential for multi- and transgenerational effects. We examined the effects of ultra-low, very low, and low-level PFAS exposure (7, 70, and 700 ng/L PFOA; 24, 240, 2400 ng/L PFOS; and stepwise mixtures) from 0–5 days post-fertilization (dpf) on larval zebrafish (Danio rerio) mortality, morphology, behavior and gene expression and fecundity in adult F0 and F1 fish. As expected, environmentally relevant PFAS levels did not affect survival. Morphological abnormalities were not observed until the F1 and F2 generations. Behavior was affected differentially by each chemical and generation. Gene expression was increasingly perturbed in each generation but consistently showed lipid pathway disruption across all generations. Dysregulation of behavior and gene expression is heritable, even in larvae with no direct or indirect exposure. This is the first report of the transgenerational effects of PFOA, PFOS, and their mixture in terms of zebrafish behavior and untargeted gene expression.
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- 2022
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43. Bacterial Patterns and Empiric Antibiotic Use in COPD Patients With Community-Acquired Pneumonia
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Sergi Pascual-Guardia, Francesco Amati, Judith Marin-Corral, Stefano Aliberti, Joaquim Gea, Nilam J. Soni, Alejandro Rodriguez, Oriol Sibila, Francisco Sanz, Giovanni Sotgiu, Pedro J. Marcos, Ane Uranga, Branislava Milenkovic, Christian N. Meyer, Martin Kolditz, Antonio R. Anzueto, and Marcos I. Restrepo
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Pulmonary and Respiratory Medicine - Abstract
Chronic obstructive pulmonary disease (COPD) is strongly associated with the development of community-acquired pneumonia (CAP). Limited data are available on risk factors for difficult to manage bacteria such as Pseudomonas aeruginosa in COPD patients with CAP. Our objective was to assess the microbiological patterns associated with risk factors that determine empiric antibiotic therapy in hospitalized COPD patients with CAP.We performed a secondary data analysis of an international, multicenter, observational, point-prevalence study involving hospitalized COPD patients with CAP from March to June 2015. After identifying the risk factors associated with different microorganisms, we developed a scoring system to guide decision-making about empiric anti-pseudomonal antibiotic therapy in this population.We enrolled 689 hospitalized COPD patients with CAP with documented microbiological testing. The most frequent microorganisms isolated were Streptococcus pneumoniae (8%) and Gram-negative bacteria (8%), P. aeruginosa (7%) and Haemophilus influenzae (3%). We developed a scoring system incorporating the variables independently associated with P. aeruginosa that include a previous P. aeruginosa isolation or infection (OR 14.2 [95%CI 5.7-35.2]), hospitalization in the past 12 months (OR 3.7 [1.5-9.2]), and bronchiectasis (OR 3.2 [1.4-7.2]). Empiric anti-pseudomonal antibiotics were overutilized in COPD patients with CAP. The new scoring system has the potential to reduce empiric anti-pseudomonal antibiotic use from 54.1% to 6.2%.COPD patients with CAP present different microbiological profiles associated with unique risk factors. Anti-pseudomonal treatment is a critical decision when selecting empiric antibiotic therapy. We developed a COPD scoring system to guide decision-making about empiric anti-pseudomonal antibiotic therapy.
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- 2022
44. Reports of the Death of Expertise may be Exaggerated
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Henri C. Santos, Michelle N. Meyer, and Christopher F. Chabris
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- 2022
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45. An illusion of predictability in scientific results
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Sam Zhang, Patrick Ryan Heck, Michelle N. Meyer, Christopher F. Chabris, Daniel G Goldstein, and Jake M. Hofman
- Abstract
Traditionally, scientists have placed more emphasis on communicating inferential uncertainty (i.e., the precision of statistical estimates) compared to outcome variability (i.e., the predictability of individual outcomes). Here we show that this can lead to sizable misperceptions about the implications of scientific results. Specifically, we present three pre-registered, randomized experiments where participants saw the same scientific findings visualized as showing only inferential uncertainty, only outcome variability, or both, and answered questions about the size and importance of findings they were shown. Our results, comprised of responses from medical professionals, professional data scientists, and tenure-track faculty, show that the prevalent form of visualizing only inferential uncertainty can lead to significant overestimates of treatment effects, even among highly trained experts. In contrast, we find that depicting both inferential uncertainty and outcome variability leads to more accurate perceptions of results while appearing to leave other subjective impressions of the results unchanged, on average.
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- 2022
- Full Text
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46. User's needs influencing HPC technologies
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E. Athanasaki, N. Meyer, M. Cestari, A.Tuncer Durak, and P. Gschwandtner
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Technical Report ,Market watch ,HPC technology ,Technology watch - Abstract
The user requirements imposed by modern challenges are influencing future High Performance Computing (HPC) technologies and use cases. This report analyses a wide range of user requirements and new technologies and their impact on European and worldwide HPC trends, in particular in the PRACE and EuroHPC ecosystems, as well as HPC infrastructures provided by member countries. Applications that did not require the use of advanced computing or for which HPC solutions were not possible due to excessive costs and availability are now available in HPC and cloud computing. The way of using computing infrastructure and its services is changing, and due to its unification and decrease of costs, the popularity of HPC and cloud computing will continue to increase. The present variety of applications significantly exceeds the scientific community and also applies to industry, governmental use and security. An additional driving force of future HPC technology originates from the policies of the European Commission and member countries’ regional needs. Big data analytics and artificial intelligence are among the identified applications, Interactivity in computing systems can also be essential for certain workflows. FPGAs and other specialized hardware or software packages are ideal for selected classes of applications. The above examples in conjunction with other requirements, outlined within this report, affects the design of HPC systems and can be used to justify the diversification of hardware and software set ups according to their target users.
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- 2022
- Full Text
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47. A single intranasal dose of human parainfluenza virus type 3-vectored vaccine induces effective antibody and memory T cell response in the lungs and protects hamsters against SARS-CoV-2
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Philipp A. Ilinykh, Sivakumar Periasamy, Kai Huang, Natalia A. Kuzmina, Palaniappan Ramanathan, Michelle N. Meyer, Chad E. Mire, Ivan V. Kuzmin, Preeti Bharaj, Jessica R. Endsley, Maria Chikina, Stuart C. Sealfon, Steven G. Widen, Mark A. Endsley, and Alexander Bukreyev
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Pharmacology ,Infectious Diseases ,viruses ,Immunology ,Pharmacology (medical) - Abstract
Respiratory tract vaccination has an advantage of needle-free delivery and induction of mucosal immune response in the portal of SARS-CoV-2 entry. We utilized human parainfluenza virus type 3 vector to generate constructs expressing the full spike (S) protein of SARS-CoV-2, its S1 subunit, or the receptor-binding domain, and tested them in hamsters as single-dose intranasal vaccines. The construct bearing full-length S induced high titers of neutralizing antibodies specific to S protein domains critical to the protein functions. Robust memory T cell responses in the lungs were also induced, which represent an additional barrier to infection and should be less sensitive than the antibody responses to mutations present in SARS-CoV-2 variants. Following SARS-CoV-2 challenge, animals were protected from the disease and detectable viral replication. Vaccination prevented induction of gene pathways associated with inflammation. These results indicate advantages of respiratory vaccination against COVID-19 and inform the design of mucosal SARS-CoV-2 vaccines.
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- 2022
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48. Coronal Fine Linear Rays: Are They Fast Streams From Active Regions?
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Serge Koutchmy, Philippe Lamy, Christian Viladrich, Boris Filippov, Arthur Nikoghossian, Leon Golub, M. Maksimovic, K. Issautier, N. Meyer-Vernet, M. Moncuquet, F. Pantellini, Institut d'Astrophysique de Paris (IAP), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Astrophysique de Marseille (LAM), and Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)
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Astrophysics::High Energy Astrophysical Phenomena ,Jets outflows and bipolar flows ,Coronal hole ,solar magnetism ,Astrophysics ,96.60.Vg ,Coronal mass ejection ,Astrophysics::Solar and Stellar Astrophysics ,Eclipse ,Physics ,solar corona ,Astronomy ,Particle emission solar wind ,96.60.Hv ,Coronal loop ,Electric and magnetic fields solar magnetism ,Helmet streamer ,Corona ,Nanoflares ,Solar wind ,astrophysical jets ,solar wind ,[SDU]Sciences of the Universe [physics] ,Physics::Space Physics ,98.58.Fd ,96.60.P - Abstract
International audience; Eclipse observations of the W-L corona show linear rays above active regions at times of solar maximum. We show that these linear rays are also observed in the field-of-view of the C2-LASCO coronagraph, in perfect correspondence with the eclipse results. A selected prominent case taken from the 2001 eclipse observation in Angola is analysed with several different methods, including the use of a synoptic map constructed using SoHO/LASCO C2 images. A clear signature of time variations near the eclipse observation is detected, suggesting that at least some parts of the beam are collimated. These observations strongly suggest high speed streams that apparently ignore the potential large scale coronal magnetic field rooted rather low in the corona. A possible origin is the neutral magnetic points located above the active region. Several mechanisms exist to explain how the plasma is accelerated in these regions to large quasi-relativistic velocities, possibly related to the occurrence of type III radio bursts. We point out a curious analogy with phenomena occurring inside coronal holes.
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- 2022
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49. Prediction of Influenza Complications: Development and Validation of a Machine Learning Prediction Model to Improve and Expand the Identification of Vaccine-Hesitant Patients at Risk of Severe Influenza Complications
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Donna M. Wolk, Alon Lanyado, Ann Marie Tice, Maheen Shermohammed, Yaron Kinar, Amir Goren, Christopher F. Chabris, Michelle N. Meyer, Avi Shoshan, and Vida Abedi
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electronic medical records ,EHR ,precision medicine ,machine learning ,decision support ,influenza ,risk stratification ,vaccine ,RT-PCR ,Clinical Lab 2.0 ,General Medicine - Abstract
Influenza vaccinations are recommended for high-risk individuals, but few population-based strategies exist to identify individual risks. Patient-level data from unvaccinated individuals, stratified into retrospective cases (n = 111,022) and controls (n = 2,207,714), informed a machine learning model designed to create an influenza risk score; the model was called the Geisinger Flu-Complications Flag (GFlu-CxFlag). The flag was created and validated on a cohort of 604,389 unique individuals. Risk scores were generated for influenza cases; the complication rate for individuals without influenza was estimated to adjust for unrelated complications. Shapley values were used to examine the model’s correctness and demonstrate its dependence on different features. Bias was assessed for race and sex. Inverse propensity weighting was used in the derivation stage to correct for biases. The GFlu-CxFlag model was compared to the pre-existing Medial EarlySign Flu Algomarker and existing risk guidelines that describe high-risk patients who would benefit from influenza vaccination. The GFlu-CxFlag outperformed other traditional risk-based models; the area under curve (AUC) was 0.786 [0.783–0.789], compared with 0.694 [0.690–0.698] (p-value < 0.00001). The presence of acute and chronic respiratory diseases, age, and previous emergency department visits contributed most to the GFlu-CxFlag model’s prediction. When higher numerical scores were assigned to more severe complications, the GFlu-CxFlag AUC increased to 0.828 [0.823–0.833], with excellent discrimination in the final model used to perform the risk stratification of the population. The GFlu-CxFlag can better identify high-risk individuals than existing models based on vaccination guidelines, thus creating a population-based risk stratification for individual risk assessment and deployment in vaccine hesitancy reduction programs in our health system.
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- 2022
50. Phenotypic and transcriptomic effects of developmental exposure to nanomolar levels of pesticides in zebrafish
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Jessica R. Blount, Jeremiah N. Shields, Chia-Chen Wu, Camille Akemann, Bridget B. Baker, Zoha Siddiqua, Danielle N. Meyer, Nemer Hijazi, Zane Tolbert, David K. Pitts, and Tracie R. Baker
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Environmental sciences ,Dieldrin ,Behavior ,animal structures ,Danio rerio ,embryonic structures ,Atrazine ,GE1-350 ,Chlorpyrifos ,Zebrafish - Abstract
This study investigates the pesticides atrazine, chlorpyrifos, and dieldrin for endocrine disrupting, phenotypic, and neurobehavioral effects. Zebrafish embryos were exposed to various environmentally relevant concentrations of pesticides during two critical windows, 0-5 days post fertilization (dpf) throughout embryogenesis and 4-5 dpf at early larval development. The toxicity of each chemical and concentration was then determined by evaluating developmental abnormalities, behavioral alterations, and transcriptomic changes. We found the most significant outcomes resulted from dieldrin exposures as low as 1 nM at 0-5 dpf, or 0.1 nM at 4−5 dpf, including abnormalities in skeleton, swim bladder, and yolk sec, as well as hyperactive behavioral phenotypes. Following dieldrin exposures at higher concentrations, 100 nM at 0-5 dpf and 1000 nM at 4−5 dpf, we observed startle movements at the transition between light and dark stimulus. The transcriptomic changes of high-level dieldrin exposures (1000 nM) implicated movement or seizure disorders. Atrazine at concentrations equal or above 100 nM led to underinflated swim bladders following exposure at 0-5 dpf. Both atrazine exposure paradigms showed transcriptomic changes related to neurological disorders and breast cancer. All chlorpyrifos exposures showed no significant morphological abnormalities and the fewest differentially expressed genes, suggesting chlorpyrifos at 0.01-100 nM exhibited the lowest toxicity among these three pesticides.
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- 2022
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