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2. Cell-Autonomous Cxcl1 Sustains Tolerogenic Circuitries and Stromal Inflammation via Neutrophil-Derived TNF in Pancreatic Cancer

Author

Anna Bianchi, Iago De Castro Silva, Nilesh U. Deshpande, Samara Singh, Siddharth Mehra, Vanessa T. Garrido, Xinyu Guo, Luis A. Nivelo, Despina S. Kolonias, Shannon J. Saigh, Eric Wieder, Christine I. Rafie, Austin R. Dosch, Zhiqun Zhou, Oliver Umland, Haleh Amirian, Ifeanyichukwu C. Ogobuiro, Jian Zhang, Yuguang Ban, Carina Shiau, Nagaraj S. Nagathihalli, Elizabeth A. Montgomery, William L. Hwang, Roberta Brambilla, Krishna Komanduri, Alejandro V. Villarino, Eneda Toska, Ben Z. Stanger, Dmitry I. Gabrilovich, Nipun B. Merchant, and Jashodeep Datta

Subjects
Oncology
Abstract

We have shown that KRAS–TP53 genomic coalteration is associated with immune-excluded microenvironments, chemoresistance, and poor survival in pancreatic ductal adenocarcinoma (PDAC) patients. By treating KRAS–TP53 cooperativity as a model for high-risk biology, we now identify cell-autonomous Cxcl1 as a key mediator of spatial T-cell restriction via interactions with CXCR2+ neutrophilic myeloid-derived suppressor cells in human PDAC using imaging mass cytometry. Silencing of cell-intrinsic Cxcl1 in LSL-KrasG12D/+;Trp53R172H/+;Pdx-1Cre/+(KPC) cells reprograms the trafficking and functional dynamics of neutrophils to overcome T-cell exclusion and controls tumor growth in a T cell–dependent manner. Mechanistically, neutrophil-derived TNF is a central regulator of this immunologic rewiring, instigating feed-forward Cxcl1 overproduction from tumor cells and cancer-associated fibroblasts (CAF), T-cell dysfunction, and inflammatory CAF polarization via transmembrane TNF–TNFR2 interactions. TNFR2 inhibition disrupts this circuitry and improves sensitivity to chemotherapy in vivo. Our results uncover cancer cell–neutrophil cross-talk in which context-dependent TNF signaling amplifies stromal inflammation and immune tolerance to promote therapeutic resistance in PDAC. Significance: By decoding connections between high-risk tumor genotypes, cell-autonomous inflammatory programs, and myeloid-enriched/T cell–excluded contexts, we identify a novel role for neutrophil-derived TNF in sustaining immunosuppression and stromal inflammation in pancreatic tumor microenvironments. This work offers a conceptual framework by which targeting context-dependent TNF signaling may overcome hallmarks of chemoresistance in pancreatic cancer.

Published
2023
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6. Differences in nomenclature usage and preference among dermatopathologists for 'dysplastic' nevi: A national survey

Author

Austin R. Green, Ata Moshiri, Daniel S. Hippe, Caroline Raymundo, Michael Piepkorn, and Michi M. Shinohara

Subjects
Histology, Dermatology, Pathology and Forensic Medicine
Abstract

Ongoing controversy exists regarding terminology used to describe atypical melanocytic nevi. Efforts to standardize nomenclature, including the 1992 NIH consensus conference, have been largely unsuccessful. Significant advances have revealed an increasingly detailed genetic picture of melanocytic neoplasms, including strong evidence for the existence of those with "intermediate" behavior.We sent an electronic survey to dermatopathologists (n=846) to assess trends in nomenclature usage and attitudes toward developing new consensus nomenclature for atypical melanocytic nevi.There were 229 complete responses (27.1% response rate). The most used/preferred nomenclature was "dysplastic nevus" (43%/39%, respectively), followed by the NIH-recommended terminology (28%/26%). Three-tier grading systems were most heavily used/preferred (79%/63%). Dermatopathologists based in New England were most likely to use the NIH terminology, whereas "dysplastic nevus" or 'other' were most used elsewhere (p=0.029). Most (76%) expressed at least "moderate" enthusiasm for developing consensus nomenclature, with 47% "very" or "extremely" enthusiastic.Little has changed with the wide variation in terminology for atypical melanocytic nevi. There continues to be no one dominant terminology in use. However, there is enthusiasm for standardization. A new attempt at updated consensus nomenclature may be fruitful.

Published
2023
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15. The Influences of a Knowledge Representation Tool on Searchers with Varying Cognitive Abilities

Author

Bogeum Choi, Jaime Arguello, Robert Capra, and Austin R. Ward

Subjects
General Business, Management and Accounting, Computer Science Applications, Information Systems
Abstract

While current systems are effective in helping searchers resolve simple information needs (e.g., fact-finding), they provide less support for searchers working on complex information-seeking tasks. Complex search tasks involve a wide range of (meta)cognitive activities, including goal-setting, organizing information, drawing inferences, monitoring progress, and revising mental models and search strategies. We report on a lab study ( N = 32) that investigated the influences of a knowledge representation tool called the OrgBox, developed to support searchers with complex tasks. The OrgBox tool was integrated into a custom-built search system and allowed study participants to drag-and-drop textual passages into the tool, organize passages into logical groupings called “boxes”, and make notes on passages and boxes. The OrgBox was compared to a baseline tool (called the Bookmark) that allowed participants to save textual passages, but not organize them nor make notes. Knowledge representation tools such as the OrgBox may provide special benefits for users with different cognitive profiles. In this article, we explore two cognitive abilities: (1) working memory (WM) capacity and (2) switching (SW) ability. Participants in the study were asked to gather information on a complex subject and produce an outline for a hypothetical research article. We investigate the influences of the tool (OrgBox vs. Bookmark) and the participant’s working memory capacity and switching ability on three types of outcomes: (RQ1) search behaviors, (RQ2) post-task perceptions, and (RQ3) the quality of outlines produces by participants.

Published
2023
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18. Patient-reported discrimination among limited-resourced cancer survivors: a brief report

Author

Nicole E. Caston, Austin R. Waters, Courtney P. Williams, Caitlin Biddell, Lisa Spees, Kathleen Gallagher, Rebekah Angove, Eric Anderson, Alan Balch, Stephanie Wheeler, and Gabrielle B. Rocque

Subjects
Psychiatry and Mental health, Oncology, Applied Psychology
Abstract

Healthcare discrimination has been associated with health disparities including lower cancer screenings, higher medical mistrust, and strained patient-provider relationships. Our study sought to understand patient-reported discrimination among cancer survivors with limited resources living in the United States.We used cross-sectional survey data distributed by the Patient Advocate Foundation (PAF) in 12/2020 and 07/2021. Respondents reported source and reason of healthcare discrimination. Age, sex, race and ethnicity, annual household income, Rural-Urban Commuting Area (RUCA), Area Deprivation Index (ADI), employment status, cancer type, and number of comorbidities were independent variables of interest. The association between these variables and patient-reported healthcare discrimination was estimated using risk ratios (RRs) and 95% confidence intervals (CIs) from a multivariable modified Poisson regression model with robust standard errors.A total of 587 cancer survivors were included in our analysis. Most respondents were female (72%) and aged ≥56 (62%); while 33% were Black, Indigenous, or Person of Color. Overall, 23% reported receipt of discrimination, with the majority reporting doctor, nurse, or healthcare provider as the source (58%). Most common reasons for discrimination included disease status (42%), income/ability to pay (36%), and race and ethnicity (17%). In the adjusted model, retired survivors were 62% less likely to report discrimination compared to those employed (RR 0.38; 95% CI 0.23-0.64). Additionally, survivors with ≥3 comorbidities were 86% more likely to report discrimination compared to those survivors with no non-cancer comorbidities (RR 1.86; 95% CI 1.26-2.72).Cancer survivors with limited resources reported substantial discrimination most often from a healthcare provider and most commonly for disease status and income. Discrimination should be mitigated to provide equitable and high-quality cancer care.

Published
2022
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23. Combined Quantification of 18F-FDG and 68Ga-DOTATATE PET/CT for Prognosis in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms

Author

Stephen E. Moore, Jennifer R. Eads, Carina Mari Aparici, Hwan Lee, Ryusuke Nakamoto, Daniel A. Pryma, and Austin R. Pantel

Subjects
Oncology, medicine.medical_specialty, PET-CT, business.industry, Proportional hazards model, External validation, Neuroendocrine tumors, medicine.disease, Well differentiated, Internal medicine, Cohort, medicine, Ki67 index, Radiology, Nuclear Medicine and imaging, 68Ga-DOTATATE, business
Abstract

Rationale and Objectives High-grade gastroenteropancreatic neuroendocrine neoplasms (G3 GEP-NENs) are pathologically classified into well differentiated neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (G3 NECs). Using a novel parameter, we examined the prognostic value of 18F-FDG and 68Ga-DOTATATE PET/CT quantification in comparison to pathologic assessment in G3 GEP-NENs. Materials and Methods A total of 31 patients with G3 GEP-NENs were reviewed. For each patient, the SUVmax on 18F-FDG and 68Ga-DOTATATE PET/CT were used to calculate the FDG-DOTATATE-Z (FDZ) score: a continuous parameter that increases with 68Ga-DOTATATE uptake and decreases with 18F-FDG uptake. The variation in the FDZ score with respect to pathologic variables was examined. Kaplan-Meier and Cox regression analyses were performed to evaluate the effect of FDZ score on overall survival. An external cohort of 21 patients was used for validation. Results The FDZ score was significantly higher in G3 NETs compared to G3 NECs (p 0.05 group showed significantly longer survival compared to those in the FDZ≤0.05 group, with median of 34.9 vs. 12.0 months (p 0.05 (p=0.005), well differentiated disease (p=0.044), and lower Ki67 index (p=0.042) were predictors of survival. On multivariate regression, only FDZ>0.05 could independently predict longer survival with HR=0.16 (p=0.018), which was reproduced in the external validation cohort. Conclusion Combined quantification of 18F-FDG and 68Ga-DOTATATE PET/CT into a novel parameter, the FDZ score, reflects the pathologic characteristics of G3 GEP-NENs and is a prognostic indicator of overall survival independent of differentiation.

Published
2022
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24. Predicting Peak Wind Gusts during Specific Weather Types with the Meteorologically Stratified Gust Factor Model

Author

Victoria A. Lang, Teresa J. Turner, Brandon R. Selbig, Austin R. Harris, and Jonathan D. W. Kahl

Subjects
Atmospheric Science
Abstract

Wind gusts present challenges to operational meteorologists, both to forecast accurately and also to verify. Strong wind gusts can damage structures and create costly risks for diverse industrial sectors. The meteorologically stratified gust factor (MSGF) model incorporates site-specific gust factors (the ratio of peak wind gust to mean wind speed) with wind speed and direction forecast guidance. The MSGF model has previously been shown to be a viable operational tool that exhibits skill (improvement over climatology) in forecasting peak wind gusts. This study assesses the performance characteristics of the MSGF model by evaluating peak gust predictions during several types of gust-producing weather phenomena. Peak wind gusts were prepared and verified for seven specific weather conditions over an 8-yr period at 16 sites across the United States. When coupled with two forms of model output statistics (MOS) wind guidance, the MSGF model generally shows skill in predicting peak wind gusts at forecast projections ranging from 6 to 72 h. The model performed best during high pressure and nocturnal conditions and was also skillful during conditions involving snow. The model did not perform well during the “rain with thunder” weather type. The MSGF model is a viable tool for the operational prediction of peak gusts for most gust-producing weather types. Significance Statement Wind gusts are an important and potentially costly environmental hazard. Wind gusts affect many industrial sectors, including transportation, power generation, forestry, construction, and insurance, but predicting gusts remains a challenging component of weather forecasting. Recent studies have demonstrated that the meteorologically stratified gust factor (MSGF) model shows skill in predicting peak gusts. This study shows that the MSGF model is skillful at predicting peak gusts during specific types of gust-producing weather phenomena at forecast projections up to 72 h, providing further confirmation that the MSGF model is a viable tool for the operational prediction of peak gusts.

Published
2022
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25. Hypergraph Cuts with General Splitting Functions

Author

Nate Veldt, Austin R. Benson, and Jon Kleinberg

Subjects
FOS: Computer and information sciences, Computer Science - Computational Complexity, Computational Mathematics, Discrete Mathematics (cs.DM), Computer Science::Discrete Mathematics, Applied Mathematics, Computer Science - Data Structures and Algorithms, Data Structures and Algorithms (cs.DS), Computational Complexity (cs.CC), Computer Science - Discrete Mathematics, MathematicsofComputing_DISCRETEMATHEMATICS, Theoretical Computer Science
Abstract

The minimum $s$-$t$ cut problem in graphs is one of the most fundamental problems in combinatorial optimization, and graph cuts underlie algorithms throughout discrete mathematics, theoretical computer science, operations research, and data science. While graphs are a standard model for pairwise relationships, hypergraphs provide the flexibility to model multi-way relationships, and are now a standard model for complex data and systems. However, when generalizing from graphs to hypergraphs, the notion of a "cut hyperedge" is less clear, as a hyperedge's nodes can be split in several ways. Here, we develop a framework for hypergraph cuts by considering the problem of separating two terminal nodes in a hypergraph in a way that minimizes a sum of penalties at split hyperedges. In our setup, different ways of splitting the same hyperedge have different penalties, and the penalty is encoded by what we call a splitting function. Our framework opens a rich space on the foundations of hypergraph cuts. We first identify a natural class of cardinality-based hyperedge splitting functions that depend only on the number of nodes on each side of the split. In this case, we show that the general hypergraph $s$-$t$ cut problem can be reduced to a tractable graph $s$-$t$ cut problem if and only if the splitting functions are submodular. We also identify a wide regime of non-submodular splitting functions for which the problem is NP-hard. We also analyze extensions to multiway cuts with at least three terminal nodes and identify a natural class of splitting functions for which the problem can be reduced in an approximation-preserving way to the node-weighted multiway cut problem in graphs, again subject to a submodularity property. Finally, we outline several open questions on general hypergraph cut problems.

Published
2022
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26. Data from Cell-Autonomous Cxcl1 Sustains Tolerogenic Circuitries and Stromal Inflammation via Neutrophil-Derived TNF in Pancreatic Cancer

Author

Jashodeep Datta, Nipun B. Merchant, Dmitry I. Gabrilovich, Ben Z. Stanger, Eneda Toska, Alejandro V. Villarino, Krishna Komanduri, Roberta Brambilla, William L. Hwang, Elizabeth A. Montgomery, Nagaraj S. Nagathihalli, Carina Shiau, Yuguang Ban, Jian Zhang, Ifeanyichukwu C. Ogobuiro, Haleh Amirian, Oliver Umland, Zhiqun Zhou, Austin R. Dosch, Christine I. Rafie, Eric Wieder, Shannon J. Saigh, Despina S. Kolonias, Luis A. Nivelo, Xinyu Guo, Vanessa T. Garrido, Siddharth Mehra, Samara Singh, Nilesh U. Deshpande, Iago De Castro Silva, and Anna Bianchi

Abstract

We have shown that KRAS–TP53 genomic coalteration is associated with immune-excluded microenvironments, chemoresistance, and poor survival in pancreatic ductal adenocarcinoma (PDAC) patients. By treating KRAS–TP53 cooperativity as a model for high-risk biology, we now identify cell-autonomous Cxcl1 as a key mediator of spatial T-cell restriction via interactions with CXCR2+ neutrophilic myeloid-derived suppressor cells in human PDAC using imaging mass cytometry. Silencing of cell-intrinsic Cxcl1 in LSL-KrasG12D/+;Trp53R172H/+;Pdx-1Cre/+(KPC) cells reprograms the trafficking and functional dynamics of neutrophils to overcome T-cell exclusion and controls tumor growth in a T cell–dependent manner. Mechanistically, neutrophil-derived TNF is a central regulator of this immunologic rewiring, instigating feed-forward Cxcl1 overproduction from tumor cells and cancer-associated fibroblasts (CAF), T-cell dysfunction, and inflammatory CAF polarization via transmembrane TNF–TNFR2 interactions. TNFR2 inhibition disrupts this circuitry and improves sensitivity to chemotherapy in vivo. Our results uncover cancer cell–neutrophil cross-talk in which context-dependent TNF signaling amplifies stromal inflammation and immune tolerance to promote therapeutic resistance in PDAC.Significance:By decoding connections between high-risk tumor genotypes, cell-autonomous inflammatory programs, and myeloid-enriched/T cell–excluded contexts, we identify a novel role for neutrophil-derived TNF in sustaining immunosuppression and stromal inflammation in pancreatic tumor microenvironments. This work offers a conceptual framework by which targeting context-dependent TNF signaling may overcome hallmarks of chemoresistance in pancreatic cancer.

Published
2023
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27. Supplementary Table S1 from Cell-Autonomous Cxcl1 Sustains Tolerogenic Circuitries and Stromal Inflammation via Neutrophil-Derived TNF in Pancreatic Cancer

Author

Jashodeep Datta, Nipun B. Merchant, Dmitry I. Gabrilovich, Ben Z. Stanger, Eneda Toska, Alejandro V. Villarino, Krishna Komanduri, Roberta Brambilla, William L. Hwang, Elizabeth A. Montgomery, Nagaraj S. Nagathihalli, Carina Shiau, Yuguang Ban, Jian Zhang, Ifeanyichukwu C. Ogobuiro, Haleh Amirian, Oliver Umland, Zhiqun Zhou, Austin R. Dosch, Christine I. Rafie, Eric Wieder, Shannon J. Saigh, Despina S. Kolonias, Luis A. Nivelo, Xinyu Guo, Vanessa T. Garrido, Siddharth Mehra, Samara Singh, Nilesh U. Deshpande, Iago De Castro Silva, and Anna Bianchi

Abstract

Differentially expressed pathways comparing transcriptomes in KRAS-TP53 co-altered (n=23) and KRAS-altered/TP53WT (n=5) derived from Cancer Cell Line Encyclopedia

Published
2023
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28. Supplementary Table S3 from Cell-Autonomous Cxcl1 Sustains Tolerogenic Circuitries and Stromal Inflammation via Neutrophil-Derived TNF in Pancreatic Cancer

Author

Jashodeep Datta, Nipun B. Merchant, Dmitry I. Gabrilovich, Ben Z. Stanger, Eneda Toska, Alejandro V. Villarino, Krishna Komanduri, Roberta Brambilla, William L. Hwang, Elizabeth A. Montgomery, Nagaraj S. Nagathihalli, Carina Shiau, Yuguang Ban, Jian Zhang, Ifeanyichukwu C. Ogobuiro, Haleh Amirian, Oliver Umland, Zhiqun Zhou, Austin R. Dosch, Christine I. Rafie, Eric Wieder, Shannon J. Saigh, Despina S. Kolonias, Luis A. Nivelo, Xinyu Guo, Vanessa T. Garrido, Siddharth Mehra, Samara Singh, Nilesh U. Deshpande, Iago De Castro Silva, and Anna Bianchi

Abstract

Co-occupied and unique target genes shared between Creb and RNApol-II in chromatin immunoprecipitation and sequencing (ChIP-seq) experiments performed in murine Kras-Trp53 cooperative KPC pancreatic cancer cells

Published
2023
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30. Cross-modality supervised image restoration enables nanoscale tracking of synaptic plasticity in living mice

Author

Yu Kang T. Xu, Austin R. Graves, Gabrielle I. Coste, Richard L. Huganir, Dwight E. Bergles, Adam S. Charles, and Jeremias Sulam

Subjects
Cell Biology, Molecular Biology, Biochemistry, Biotechnology
Abstract

Learning is thought to involve changes in glutamate receptors at synapses, submicron structures that mediate communication between neurons in the central nervous system. Due to their small size and high density, synapses are difficult to resolve in vivo, limiting our ability to directly relate receptor dynamics to animal behavior. Here we developed a combination of computational and biological methods to overcome these challenges. First, we trained a deep-learning image-restoration algorithm that combines the advantages of ex vivo super-resolution and in vivo imaging modalities to overcome limitations specific to each optical system. When applied to in vivo images from transgenic mice expressing fluorescently labeled glutamate receptors, this restoration algorithm super-resolved synapses, enabling the tracking of behavior-associated synaptic plasticity with high spatial resolution. This method demonstrates the capabilities of image enhancement to learn from ex vivo data and imaging techniques to improve in vivo imaging resolution.

Published
2023
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32. Evidence for the efficacy of pre-harvest agricultural practices in mitigating food-safety risks to fresh produce in North America

Author

Naresh Devarajan, Daniel L. Weller, Matthew Jones, Aiko D. Adell, Achyut Adhikari, Ana Allende, Nicole L. Arnold, Patrick Baur, Sarah M. Beno, Donna Clements, Elissa M. Olimpi, Faith Critzer, Hyatt Green, Lisa Gorski, Angela Ferelli Gruber, Jasna Kovac, Jeffery McGarvey, Claire M. Murphy, Sarah I. Murphy, Nora Navarro-Gonzalez, Jeb P. Owen, Alda F. A. Pires, Nicole Richard, Sandipan Samaddar, Radomir Schmidt, Kate Scow, Nikki W. Shariat, Olivia M. Smith, Austin R. Spence, Don Stoeckel, Thao D. H. Tran, Gretchen Wall, and Daniel S. Karp

Subjects
Global and Planetary Change, Ecology, Horticulture, Management, Monitoring, Policy and Law, Agronomy and Crop Science, Food Science
Abstract

Consumption of contaminated produce remains a leading cause of foodborne illness. Increasingly, growers are altering agricultural practices and farm environments to manage food-safety hazards, but these changes often result in substantial economic, social, and environmental costs. Here, we present a comprehensive evidence synthesis evaluating the efficacy of soil, non-crop vegetation, animal, landscape, and irrigation water management strategies aimed at reducing produce-safety risk in North America. We systematically summarized findings from 78 peer-reviewed papers on the effect of 21 management practices on the prevalence, abundance, or survival of four foodborne pathogens (i.e., E. coli, Salmonella spp., Listeria spp., and Campylobacter spp.), resulting in 113 summaries. We then organized a 30-member expert panel, who used these summaries to evaluate the impact of each practice on food-safety outcomes. While more than half of the practices were too understudied to confidently evaluate their impact on food safety, the panel did identify several practices that were associated with reduced preharvest food-safety risks, including not using raw manure, separating crop and livestock production, and choosing low-risk irrigation sources. The panel also identified practices that appear ineffective at reducing food-safety risks, such as the removal of non-crop vegetation. Overall, these findings provide insights into the food-safety impacts of agricultural and land management practices that growers, auditors, and extension personnel can use to co-manage produce preharvest environments for food safety and other aims.

Published
2023
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34. 177Lu-PSMA Therapy

Author

Ephraim E. Parent, Bital Savir-Baruch, Isis W. Gayed, Frankis Almaguel, Bennett B. Chin, Austin R. Pantel, Evan Armstrong, Amanda Morley, Robin C. Ippisch, and Robert R. Flavell

Subjects
Radiological and Ultrasound Technology, Radiology, Nuclear Medicine and imaging, General Medicine
Published
2022
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36. Parasitism of Enallagma civile Hagen in Selys, 1853 (Zygoptera: Coenagrionidae) by Arrenurus water mites

Author

Austin R. Biddy and Nancy E. McIntyre

Subjects
Insect Science, Ecology, Evolution, Behavior and Systematics
Abstract

We compared the prevalence and intensity of Arrenurus sensu stricto water mite parasites on Enallagma civile Hagen in Selys, 1853 (Zygoptera: Coenagrionidae) from 10 freshwater wetlands (playas) in two different land-cover contexts in western Texas from 2006-2007. Vulnerability to parasitism may be a consequence of disturbance, so we predicted that the more natural form of regional land cover (grasslands) surrounding playas should be associated with a lower water mite load than more disturbed land cover (tilled croplands). Additionally, we examined Arrenurus occurrence and intensity of infection by host sex. Overall prevalence was 38.46% of 130 damselflies sampled having mites; this varied by land-cover type but with opposite trends between years. Overall average parasite load was ~11 water mites per infected host (range: 1-40 mites); intensity was significantly higher in hosts from cropland playas in 2006, but there was no difference by surrounding land cover in 2007. Although there were consistent trends in both years of more males being parasitized than females, the highly uneven distribution of parasites on hosts and differences in average mite load between years generated variability that obscured any statistically significant patterns. Thus, land-cover context surrounding playas, but not host sex, had an impact on parasite load in one of the two years of our study. Future work is needed to identify the mechanisms by which land cover may affect water mite-odonate host-parasite relationships as well as the role of the odonate assemblage as a whole in dispersal of parasites in a temporally dynamic wetland network.

Published
2022
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37. A qualitative inquiry of communication based barriers to the diagnosis of pediatric cancer: Perceptions of primarily Spanish-speaking caregivers

Author

Eduardo R. Zamora, Austin R. Waters, Jennyffer Morales, Anne C. Kirchhoff, Guadalupe E Tovar, Vannina Gwilliam, Mark Fluchel, Stephanie Rosen, and Echo L. Warner

Subjects
medicine.medical_specialty, Cultural humility, Communication, media_common.quotation_subject, Communication Barriers, Language barrier, Cancer, General Medicine, medicine.disease, Pediatric cancer, Focus group, Dehumanization, Caregivers, Neoplasms, Family medicine, Perception, Pediatric oncology, medicine, Humans, Child, Psychology, Language, media_common
Abstract

Background Primarily Spanish-speaking cancer patients and caregivers often experience non-congruence with healthcare providers about beliefs, values, and knowledge of cancer. Our goal was to describe how communication related to the diagnosis of cancer was influenced by culture and language among primarily Spanish-speaking caregivers of pediatric cancer patients. Methods Caregivers participated in three focus groups about their experiences with their child's diagnosis, communication issues, and understanding of their child's diagnosis and treatment plan. Focus groups were audio recorded, transcribed, and qualitatively analyzed using interpretive description. Results Three themes emerged: 1) Negative experiences and barriers during the cancer diagnosis and treatment, 2) Miscommunication and system complexity, and 3) Language barriers throughout the diagnostic process. Due to barriers and negative experiences, some caregivers reported that their child's diagnosis was delayed, that providers sometimes used dehumanizing language, and that they were confused about diagnostic testing and treatment. Conclusion Cultural and linguistic disparities in pediatric oncology must be systematically addressed at the provider, clinic, and system level. Practice implications High-quality cancer care delivered by oncologists and cancer care teams should include cultural humility when discussing the cancer diagnosis and prognosis.

Published
2022
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38. Fauci-Email: A JSON Digest of Anthony Fauci’s Released Emails

Author

Austin R. Benson, Nate Veldt, and David F. Gleich

Abstract

A collection of over 3000 pages of emails sent by Anthony Fauci and his staff were released in an effort to understand the United States government response to the COVID-19 pandemic. In this paper, we describe how the original PDF document of emails was translated into a resource consisting of json files that make many future studies easy. We include examples for how to convert this email information into a network, a hypergraph, a temporal sequence, and a tensor for subsequent analysis, and discuss use cases and benefits in analyzing the data in these different derived formats. These resources are broadly useful for future research and pedagogical uses in terms of human and system behavioral interactions.

Published
2022
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40. Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Author

Romiti, Giulio Francesco, Proietti, Marco, Vitolo, Marco, Bonini, Niccolò, Fawzy, Ameenathul Mazaya, Ding, Wern Yew, Fauchier, Laurent, Marin, Francisco, Nabauer, Michael, Dan, Gheorghe Andrei, Potpara, Tatjana S., Boriani, Giuseppe, Lip, Gregory Y. H., Tavazzi, L., Maggioni, A. P., Kalarus, Z., Ferrari, R., Shantsila, A., Goda, A., Mairesse, G., Shalganov, T., Antoniades, L., Taborsky, M., Riahi, S., Muda, P., García Bolao, I., Piot, O., Etsadashvili, K., Simantirakis, E. N., Haim, M., Azhari, A., Najafian, J., Santini, M., Mirrakhimov, E., Kulzida, K., Erglis, A., Poposka, L., Burg, M. R., Crijns, H., Erküner, Atar, D., Lenarczyk, R., Oliveira, M. Martins, Shah, D., Serdechnaya, E., Diker, E., Lane, D., Zëra, E., Ekmekçiu, U., Paparisto, V., Tase, M., Gjergo, H., Dragoti, J., Ciutea, M., Ahadi, N., el Husseini, Z., Raepers, M., Leroy, J., Haushan, P., Jourdan, A., Lepiece, C., Desteghe, L., Vijgen, J., Koopman, P., van Genechten, G., Heidbuchel, H., Boussy, T., de Coninck, M., van Eeckhoutte, H., Bouckaert, N., Friart, A., Boreux, J., Arend, C., Evrard, P., Stefan, L., Hoffer, E., Herzet, J., Massoz, M., Celentano, C., Sprynger, M., Pierard, L., Melon, P., van Hauwaert, B., Kuppens, C., Faes, D., van Lier, D., van Dorpe, A., Gerardy, A., Deceuninck, O., Xhaet, O., Dormal, F., Ballant, E., Blommaert, D., Yakova, D., Hristov, M., Yncheva, T., Stancheva, N., Tisheva, S., Tokmakova, M., Nikolov, F., Gencheva, D., Kunev, B., Stoyanov, M., Marchov, D., Gelev, V., Traykov, V., Kisheva, A., Tsvyatkov, H., Shtereva, R., Bakalska-Georgieva, S., Slavcheva, S., Yotov, Y., Kubíčková, M., Joensen, A. Marni, Gammelmark, A., Rasmussen, L. Hvilsted, Dinesen, P., Venø, S. Krogh, Sorensen, B., Korsgaard, A., Andersen, K., Hellum, C. 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L., Mussagaliyeva, A., Ahyt, B., Salihova, Z., Koshum-Bayeva, K., Kerimkulova, A., Bairamukova, A., Lurina, B., Zuzans, R., Jegere, S., Mintale, I., Kupics, K., Jubele, K., Kalejs, O., Vanhear, K., Burg, M., Cachia, M., Abela, E., Warwicker, S., Tabone, T., Xuereb, R., Asanovic, D., Drakalovic, D., Vukmirovic, M., Pavlovic, N., Music, L., Bulatovic, N., Boskovic, A., Uiterwaal, H., Bijsterveld, N., de Groot, J., Neefs, J., van den Berg, N., Piersma, F., Wilde, A., Hagens, V., van Es, J., van Opstal, J., van Rennes, B., Verheij, H., Breukers, W., Tjeerdsma, G., Nijmeijer, R., Wegink, D., Binnema, R., Said, S., Philippens, S., van Doorn, W., Szili-Torok, T., Bhagwandien, R., Janse, P., Muskens, A., van Eck, M., Gevers, R., van der Ven, N., Duygun, A., Rahel, B., Meeder, J., Vold, A., Holst Hansen, C., Engset, I., Dyduch-Fejklowicz, B., Koba, E., Cichocka, M., Sokal, A., Kubicius, A., Pruchniewicz, E., Kowalik-Sztylc, A., Czapla, W., Mróz, I., Kozlowski, M., Pawlowski, T., Tendera, M., Winiarska-Filipek, A., Fidyk, A., Slowikowski, A., Haberka, M., Lachor-Broda, M., Biedron, M., Gasior, Z., Kołodziej, M., Janion, M., Gorczyca-Michta, I., Wozakowska-Kaplon, B., Stasiak, M., Jakubowski, P., Ciurus, T., Drozdz, J., Simiera, M., Zajac, P., Wcislo, T., Zycinski, P., Kasprzak, J., Olejnik, A., Harc-Dyl, E., Miarka, J., Pasieka, M., Ziemińska-Łuć, M., Bujak, W., Śliwiński, A., Grech, A., Morka, J., Petrykowska, K., Prasał, M., Hordyński, G., Feusette, P., Lipski, P., Wester, A., Streb, W., Romanek, J., Woźniak, P., Chlebuś, M., Szafarz, P., Stanik, W., Zakrzewski, M., Kaźmierczak, J., Przybylska, A., Skorek, E., Błaszczyk, H., Stępień, M., Szabowski, S., Krysiak, W., Szymańska, M., Karasiński, J., Blicharz, J., Skura, M., Hałas, K., Michalczyk, L., Orski, Z., Krzyżanowski, K., Skrobowski, A., Zieliński, L., Tomaszewska-Kiecana, M., Dłużniewski, M., Kiliszek, M., Peller, M., Budnik, M., Balsam, P., Opolski, G., Tymińska, A., Ozierański, K., Wancerz, A., Borowiec, A., Majos, E., Dabrowski, R., Szwed, H., Musialik-Lydka, A., Leopold-Jadczyk, A., Jedrzejczyk-Patej, E., Koziel, M., Mazurek, M., Krzemien-Wolska, K., Starosta, P., Nowalany-Kozielska, E., Orzechowska, A., Szpot, M., Staszel, M., Almeida, S., Pereira, H., Brandão Alves, L., Miranda, R., Ribeiro, L., Costa, F., Morgado, F., Carmo, P., Galvao Santos, P., Bernardo, R., Adragão, P., Ferreira da Silva, G., Peres, M., Alves, M., Leal, M., Cordeiro, A., Magalhães, P., Fontes, P., Leão, S., Delgado, A., Costa, A., Marmelo, B., Rodrigues, B., Moreira, D., Santos, J., Santos, L., Terchet, A., Darabantiu, D., Mercea, S., Turcin Halka, V., Pop Moldovan, A., Gabor, A., Doka, B., Catanescu, G., Rus, H., Oboroceanu, L., Bobescu, E., Popescu, R., Dan, A., Buzea, A., Daha, I., Dan, G., Neuhoff, I., Baluta, M., Ploesteanu, R., Dumitrache, N., Vintila, M., Daraban, A., Japie, C., Badila, E., Tewelde, H., Hostiuc, M., Frunza, S., Tintea, E., Bartos, D., Ciobanu, A., Popescu, I., Toma, N., Gherghinescu, C., Cretu, D., Patrascu, N., Stoicescu, C., Udroiu, C., Bicescu, G., Vintila, V., Vinereanu, D., Cinteza, M., Rimbas, R., Grecu, M., Cozma, A., Boros, F., Ille, M., Tica, O., Tor, R., Corina, A., Jeewooth, A., Maria, B., Georgiana, C., Natalia, C., Alin, D., Dinu-Andrei, D., Livia, M., Daniela, R., Larisa, R., Umaar, S., Tamara, T., Popescu, M. Ioachim, Nistor, D., Sus, I., Coborosanu, O., Alina-Ramona, N., Dan, R., Petrescu, L., Ionescu, G., Vacarescu, C., Goanta, E., Mangea, M., Ionac, A., Mornos, C., Cozma, D., Pescariu, S., Solodovnicova, E., Soldatova, I., Shutova, J., Tjuleneva, L., Zubova, T., Uskov, V., Obukhov, D., Rusanova, G., Isakova, N., Odinsova, S., Arhipova, T., Kazakevich, E., Zavyalova, O., Novikova, T., Riabaia, I., Zhigalov, S., Drozdova, E., Luchkina, I., Monogarova, Y., Hegya, D., Rodionova, L., Nevzorova, V., Lusanova, O., Arandjelovic, A., Toncev, D., Milanov, M., Sekularac, N., Zdravkovic, M., Hinic, S., Dimkovic, S., Acimovic, T., Saric, J., Polovina, M., Vujisic-Tesic, B., Nedeljkovic, M., Zlatar, M., Asanin, M., Vasic, V., Popovic, Z., Djikic, D., Sipic, M., Peric, V., Dejanovic, B., Milosevic, N., Stevanovic, A., Andric, A., Pencic, B., Pavlovic-Kleut, M., Celic, V., Pavlovic, M., Petrovic, M., Vuleta, M., Petrovic, N., Simovic, S., Savovic, Z., Milanov, S., Davidovic, G., Iric-Cupic, V., Simonovic, D., Stojanovic, M., Stojanovic, S., Mitic, V., Ilic, V., Petrovic, D., Deljanin Ilic, M., Ilic, S., Stoickov, V., Markovic, S., Kovacevic, S., García Fernandez, A., Perez Cabeza, A., Anguita, M., Tercedor Sanchez, L., Mau, E., Loayssa, J., Ayarra, M., Carpintero, M., Roldán Rabadan, I., Ortega, M. Gil, Tello Montoliu, A., Orenes Piñero, E., Manzano Fernández, S., Marín, F., Romero Aniorte, A., Veliz Martínez, A., Quintana Giner, M., Ballesteros, G., Palacio, M., Alcalde, O., García-Bolao, I., Bertomeu Gonzalez, V., Otero-Raviña, F., García Seara, J., Gonzalez Juanatey, J., Dayal, N., Maziarski, P., Gentil-Baron, P., Koç, M., Onrat, E., Dural, I. E., Yilmaz, K., Özin, B., Kurklu, S. Tan, Atmaca, Y., Canpolat, U., Tokgozoglu, L., Dolu, A. K., Demirtas, B., Sahin, D., Ozcan Celebi, O., Gagirci, G., Turk, U. O., Ari, H., Polat, N., Toprak, N., Sucu, M., Akin Serdar, O., Taha Alper, A., Kepez, A., Yuksel, Y., Uzunselvi, A., Yuksel, S., Sahin, M., Kayapinar, O., Ozcan, T., Kaya, H., Yilmaz, M. 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Grant, S., Wilson, A., Hawksworth, C., Alam, I., Robinson, M., Ryan, S., Egdell, R., Gibson, E., Holland, M., Leonard, D., Mishra, B., Ahmad, S., Randall, H., Hill, J., Reid, L., George, M., McKinley, S., Brockway, L., Milligan, W., Sobolewska, J., Muir, J., Tuckis, L., Winstanley, L., Jacob, P., Kaye, S., Morby, L., Jan, A., Sewell, T., Boos, C., Wadams, B., Cope, C., Jefferey, P., Andrews, N., Getty, A., Suttling, A., Turner, C., Hudson, K., Austin, R., Howe, S., Iqbal, R., Gandhi, N., Brophy, K., Mirza, P., Willard, E., Collins, S., Ndlovu, N., Subkovas, E., Karthikeyan, V., Waggett, L., Wood, A., Bolger, A., Stockport, J., Evans, L., Harman, E., Starling, J., Williams, L., Saul, V., Sinha, M., Bell, L., Tudgay, S., Kemp, S., Frost, L., Ingram, T., Loughlin, A., Adams, C., Adams, M., Hurford, F., Owen, C., Miller, C., Donaldson, D., Tivenan, H., Button, H., Nasser, A., Jhagra, O., Stidolph, B., Brown, C., Livingstone, C., Duffy, M., Madgwick, P., Roberts, P., Greenwood, E., Fletcher, L., Beveridge, M., Earles, S., McKenzie, D., Beacock, D., Dayer, M., Seddon, M., Greenwell, D., Luxton, F., Venn, F., Mills, H., Rewbury, J., James, K., Roberts, K., Tonks, L., Felmeden, D., Taggu, W., Summerhayes, A., Hughes, D., Sutton, J., Felmeden, L., Khan, M., Walker, E., Norris, L., O’Donohoe, L., Mozid, A., Dymond, H., Lloyd-Jones, H., Saunders, G., Simmons, D., Coles, D., Cotterill, D., Beech, S., Kidd, S., Wrigley, B., Petkar, S., Smallwood, A., Jones, R., Radford, E., Milgate, S., Metherell, S., Cottam, V., Buckley, C., Broadley, A., Wood, D., Allison, J., Rennie, K., Balian, L., Howard, L., Pippard, L., Board, S., Pitt-Kerby, T., Romiti G.F., Proietti M., Vitolo M., Bonini N., Fawzy A.M., Ding W.Y., Fauchier L., Marin F., Nabauer M., Dan G.A., Potpara T.S., Boriani G., Lip G.Y.H., Tavazzi L., Maggioni A.P., Kalarus Z., Ferrari R., Shantsila A., Goda A., Mairesse G., Shalganov T., Antoniades L., Taborsky M., Riahi S., Muda P., Garcia Bolao I., Piot O., Etsadashvili K., Simantirakis E.N., Haim M., Azhari A., Najafian J., Santini M., Mirrakhimov E., Kulzida K., Erglis A., Poposka L., Burg M.R., Crijns H., Erkuner O., Atar D., Lenarczyk R., Oliveira M.M., Shah D., Serdechnaya E., Diker E., Lane D., Zera E., Ekmekciu U., Paparisto V., Tase M., Gjergo H., Dragoti J., Ciutea M., Ahadi N., el Husseini Z., Raepers M., Leroy J., Haushan P., Jourdan A., Lepiece C., Desteghe L., Vijgen J., Koopman P., Van Genechten G., Heidbuchel H., Boussy T., De Coninck M., Van Eeckhoutte H., Bouckaert N., Friart A., Boreux J., Arend C., Evrard P., Stefan L., Hoffer E., Herzet J., Massoz M., Celentano C., Sprynger M., Pierard L., Melon P., Van Hauwaert B., Kuppens C., Faes D., Van Lier D., Van Dorpe A., Gerardy A., Deceuninck O., Xhaet O., Dormal F., Ballant E., Blommaert D., Yakova D., Hristov M., Yncheva T., Stancheva N., Tisheva S., Tokmakova M., Nikolov F., Gencheva D., Kunev B., Stoyanov M., Marchov D., Gelev V., Traykov V., Kisheva A., Tsvyatkov H., Shtereva R., Bakalska-Georgieva S., Slavcheva S., Yotov Y., Kubickova M., Joensen A.M., Gammelmark A., Rasmussen L.H., Dinesen P., Veno S.K., Sorensen B., Korsgaard A., Andersen K., Hellum C.F., Svenningsen A., Nyvad O., Wiggers P., May O., Aarup A., Graversen B., Jensen L., Andersen M., Svejgaard M., Vester S., Hansen S., Lynggaard V., Ciudad M., Vettus R., Maestre A., Castano S., Cheggour S., Poulard J., Mouquet V., Leparree S., Bouet J., Taieb J., Doucy A., Duquenne H., Furber A., Dupuis J., Rautureau J., Font M., Damiano P., Lacrimini M., Abalea J., Boismal S., Menez T., Mansourati J., Range G., Gorka H., Laure C., Vassaliere C., Elbaz N., Lellouche N., Djouadi K., Roubille F., Dietz D., Davy J., Granier M., Winum P., Leperchois-Jacquey C., Kassim H., Marijon E., Le Heuzey J., Fedida J., Maupain C., Himbert C., Gandjbakhch E., Hidden-Lucet F., Duthoit G., Badenco N., Chastre T., Waintraub X., Oudihat M., Lacoste J., Stephan C., Bader H., Delarche N., Giry L., Arnaud D., Lopez C., Boury F., Brunello I., Lefevre M., Mingam R., Haissaguerre M., Le Bidan M., Pavin D., Le Moal V., Leclercq C., Beitar T., Martel I., Schmid A., Sadki N., Romeyer-Bouchard C., Da Costa A., Arnault I., Boyer M., Piat C., Lozance N., Nastevska S., Doneva A., Fortomaroska Milevska B., Sheshoski B., Petroska K., Taneska N., Bakrecheski N., Lazarovska K., Jovevska S., Ristovski V., Antovski A., Lazarova E., Kotlar I., Taleski J., Kedev S., Zlatanovik N., Jordanova S., Bajraktarova Proseva T., Doncovska S., Maisuradze D., Esakia A., Sagirashvili E., Lartsuliani K., Natelashvili N., Gumberidze N., Gvenetadze R., Gotonelia N., Kuridze N., Papiashvili G., Menabde I., Gloggler S., Napp A., Lebherz C., Romero H., Schmitz K., Berger M., Zink M., Koster S., Sachse J., Vonderhagen E., Soiron G., Mischke K., Reith R., Schneider M., Rieker W., Boscher D., Taschareck A., Beer A., Oster D., Ritter O., Adamczewski J., Walter S., Frommhold A., Luckner E., Richter J., Schellner M., Landgraf S., Bartholome S., Naumann R., Schoeler J., Westermeier D., William F., Wilhelm K., Maerkl M., Oekinghaus R., Denart M., Kriete M., Tebbe U., Scheibner T., Gruber M., Gerlach A., Beckendorf C., Anneken L., Arnold M., Lengerer S., Bal Z., Uecker C., Fortsch H., Fechner S., Mages V., Martens E., Methe H., Schmidt T., Schaeffer B., Hoffmann B., Moser J., Heitmann K., Willems S., Klaus C., Lange I., Durak M., Esen E., Mibach F., Mibach H., Utech A., Gabelmann M., Stumm R., Landle V., Gartner C., Goerg C., Kaul N., Messer S., Burkhardt D., Sander C., Orthen R., Kaes S., Baumer A., Dodos F., Barth A., Schaeffer G., Gaertner J., Winkler J., Fahrig A., Aring J., Wenzel I., Steiner S., Kliesch A., Kratz E., Winter K., Schneider P., Haag A., Mutscher I., Bosch R., Taggeselle J., Meixner S., Schnabel A., Shamalla A., Hotz H., Korinth A., Rheinert C., Mehltretter G., Schon B., Schon N., Starflinger A., Englmann E., Baytok G., Laschinger T., Ritscher G., Gerth A., Dechering D., Eckardt L., Kuhlmann M., Proskynitopoulos N., Brunn J., Foth K., Axthelm C., Hohensee H., Eberhard K., Turbanisch S., Hassler N., Koestler A., Stenzel G., Kschiwan D., Schwefer M., Neiner S., Hettwer S., Haeussler-Schuchardt M., Degenhardt R., Sennhenn S., Brendel M., Stoehr A., Widjaja W., Loehndorf S., Logemann A., Hoskamp J., Grundt J., Block M., Ulrych R., Reithmeier A., Panagopoulos V., Martignani C., Bernucci D., Fantecchi E., Diemberger I., Ziacchi M., Biffi M., Cimaglia P., Frisoni J., Giannini I., Boni S., Fumagalli S., Pupo S., Di Chiara A., Mirone P., Pesce F., Zoccali C., Malavasi V.L., Mussagaliyeva A., Ahyt B., Salihova Z., Koshum-Bayeva K., Kerimkulova A., Bairamukova A., Lurina B., Zuzans R., Jegere S., Mintale I., Kupics K., Jubele K., Kalejs O., Vanhear K., Burg M., Cachia M., Abela E., Warwicker S., Tabone T., Xuereb R., Asanovic D., Drakalovic D., Vukmirovic M., Pavlovic N., Music L., Bulatovic N., Boskovic A., Uiterwaal H., Bijsterveld N., De Groot J., Neefs J., van den Berg N., Piersma F., Wilde A., Hagens V., Van Es J., Van Opstal J., Van Rennes B., Verheij H., Breukers W., Tjeerdsma G., Nijmeijer R., Wegink D., Binnema R., Said S., Philippens S., van Doorn W., Szili-Torok T., Bhagwandien R., Janse P., Muskens A., van Eck M., Gevers R., van der Ven N., Duygun A., Rahel B., Meeder J., Vold A., Holst Hansen C., Engset I., Dyduch-Fejklowicz B., Koba E., Cichocka M., Sokal A., Kubicius A., Pruchniewicz E., Kowalik-Sztylc A., Czapla W., Mroz I., Kozlowski M., Pawlowski T., Tendera M., Winiarska-Filipek A., Fidyk A., Slowikowski A., Haberka M., Lachor-Broda M., Biedron M., Gasior Z., Kolodziej M., Janion M., Gorczyca-Michta I., Wozakowska-Kaplon B., Stasiak M., Jakubowski P., Ciurus T., Drozdz J., Simiera M., Zajac P., Wcislo T., Zycinski P., Kasprzak J., Olejnik A., Harc-Dyl E., Miarka J., Pasieka M., Zieminska-Luc M., Bujak W., Sliwinski A., Grech A., Morka J., Petrykowska K., Prasal M., Hordynski G., Feusette P., Lipski P., Wester A., Streb W., Romanek J., Wozniak P., Chlebus M., Szafarz P., Stanik W., Zakrzewski M., Kazmierczak J., Przybylska A., Skorek E., Blaszczyk H., Stepien M., Szabowski S., Krysiak W., Szymanska M., Karasinski J., Blicharz J., Skura M., Halas K., Michalczyk L., Orski Z., Krzyzanowski K., Skrobowski A., Zielinski L., Tomaszewska-Kiecana M., Dluzniewski M., Kiliszek M., Peller M., Budnik M., Balsam P., Opolski G., Tyminska A., Ozieranski K., Wancerz A., Borowiec A., Majos E., Dabrowski R., Szwed H., Musialik-Lydka A., Leopold-Jadczyk A., Jedrzejczyk-Patej E., Koziel M., Mazurek M., Krzemien-Wolska K., Starosta P., Nowalany-Kozielska E., Orzechowska A., Szpot M., Staszel M., Almeida S., Pereira H., Brandao Alves L., Miranda R., Ribeiro L., Costa F., Morgado F., Carmo P., Galvao Santos P., Bernardo R., Adragao P., Ferreira da Silva G., Peres M., Alves M., Leal M., Cordeiro A., Magalhaes P., Fontes P., Leao S., Delgado A., Costa A., Marmelo B., Rodrigues B., Moreira D., Santos J., Santos L., Terchet A., Darabantiu D., Mercea S., Turcin Halka V., Pop Moldovan A., Gabor A., Doka B., Catanescu G., Rus H., Oboroceanu L., Bobescu E., Popescu R., Dan A., Buzea A., Daha I., Dan G., Neuhoff I., Baluta M., Ploesteanu R., Dumitrache N., Vintila M., Daraban A., Japie C., Badila E., Tewelde H., Hostiuc M., Frunza S., Tintea E., Bartos D., Ciobanu A., Popescu I., Toma N., Gherghinescu C., Cretu D., Patrascu N., Stoicescu C., Udroiu C., Bicescu G., Vintila V., Vinereanu D., Cinteza M., Rimbas R., Grecu M., Cozma A., Boros F., Ille M., Tica O., Tor R., Corina A., Jeewooth A., Maria B., Georgiana C., Natalia C., Alin D., Dinu-Andrei D., Livia M., Daniela R., Larisa R., Umaar S., Tamara T., Popescu M.I., Nistor D., Sus I., Coborosanu O., Alina-Ramona N., Dan R., Petrescu L., Ionescu G., Vacarescu C., Goanta E., Mangea M., Ionac A., Mornos C., Cozma D., Pescariu S., Solodovnicova E., Soldatova I., Shutova J., Tjuleneva L., Zubova T., Uskov V., Obukhov D., Rusanova G., Isakova N., Odinsova S., Arhipova T., Kazakevich E., Zavyalova O., Novikova T., Riabaia I., Zhigalov S., Drozdova E., Luchkina I., Monogarova Y., Hegya D., Rodionova L., Nevzorova V., Lusanova O., Arandjelovic A., Toncev D., Milanov M., Sekularac N., Zdravkovic M., Hinic S., Dimkovic S., Acimovic T., Saric J., Polovina M., Vujisic-Tesic B., Nedeljkovic M., Zlatar M., Asanin M., Vasic V., Popovic Z., Djikic D., Sipic M., Peric V., Dejanovic B., Milosevic N., Stevanovic A., Andric A., Pencic B., Pavlovic-Kleut M., Celic V., Pavlovic M., Petrovic M., Vuleta M., Petrovic N., Simovic S., Savovic Z., Milanov S., Davidovic G., Iric-Cupic V., Simonovic D., Stojanovic M., Stojanovic S., Mitic V., Ilic V., Petrovic D., Deljanin Ilic M., Ilic S., Stoickov V., Markovic S., Kovacevic S., Garcia Fernandez A., Perez Cabeza A., Anguita M., Tercedor Sanchez L., Mau E., Loayssa J., Ayarra M., Carpintero M., Roldan Rabadan I., Ortega M.G., Tello Montoliu A., Orenes Pinero E., Manzano Fernandez S., Romero Aniorte A., Veliz Martinez A., Quintana Giner M., Ballesteros G., Palacio M., Alcalde O., Garcia-Bolao I., Bertomeu Gonzalez V., Otero-Ravina F., Garcia Seara J., Gonzalez Juanatey J., Dayal N., Maziarski P., Gentil-Baron P., Koc M., Onrat E., Dural I.E., Yilmaz K., Ozin B., Kurklu S.T., Atmaca Y., Canpolat U., Tokgozoglu L., Dolu A.K., Demirtas B., Sahin D., Ozcan Celebi O., Gagirci G., Turk U.O., Ari H., Polat N., Toprak N., Sucu M., Akin Serdar O., Taha Alper A., Kepez A., Yuksel Y., Uzunselvi A., Yuksel S., Sahin M., Kayapinar O., Ozcan T., Kaya H., Yilmaz M.B., Kutlu M., Demir M., Gibbs C., Kaminskiene S., Bryce M., Skinner A., Belcher G., Hunt J., Stancombe L., Holbrook B., Peters C., Tettersell S., Senoo K., Russell K., Domingos P., Hussain S., Partridge J., Haynes R., Bahadur S., Brown R., McMahon S., McDonald J., Balachandran K., Singh R., Garg S., Desai H., Davies K., Goddard W., Galasko G., Rahman I., Chua Y., Payne O., Preston S., Brennan O., Pedley L., Whiteside C., Dickinson C., Brown J., Jones K., Benham L., Brady R., Buchanan L., Ashton A., Crowther H., Fairlamb H., Thornthwaite S., Relph C., McSkeane A., Poultney U., Kelsall N., Rice P., Wilson T., Wrigley M., Kaba R., Patel T., Young E., Law J., Runnett C., Thomas H., McKie H., Fuller J., Pick S., Sharp A., Hunt A., Thorpe K., Hardman C., Cusack E., Adams L., Hough M., Keenan S., Bowring A., Watts J., Zaman J., Goffin K., Nutt H., Beerachee Y., Featherstone J., Mills C., Pearson J., Stephenson L., Grant S., Wilson A., Hawksworth C., Alam I., Robinson M., Ryan S., Egdell R., Gibson E., Holland M., Leonard D., Mishra B., Ahmad S., Randall H., Hill J., Reid L., George M., McKinley S., Brockway L., Milligan W., Sobolewska J., Muir J., Tuckis L., Winstanley L., Jacob P., Kaye S., Morby L., Jan A., Sewell T., Boos C., Wadams B., Cope C., Jefferey P., Andrews N., Getty A., Suttling A., Turner C., Hudson K., Austin R., Howe S., Iqbal R., Gandhi N., Brophy K., Mirza P., Willard E., Collins S., Ndlovu N., Subkovas E., Karthikeyan V., Waggett L., Wood A., Bolger A., Stockport J., Evans L., Harman E., Starling J., Williams L., Saul V., Sinha M., Bell L., Tudgay S., Kemp S., Frost L., Ingram T., Loughlin A., Adams C., Adams M., Hurford F., Owen C., Miller C., Donaldson D., Tivenan H., Button H., Nasser A., Jhagra O., Stidolph B., Brown C., Livingstone C., Duffy M., Madgwick P., Roberts P., Greenwood E., Fletcher L., Beveridge M., Earles S., McKenzie D., Beacock D., Dayer M., Seddon M., Greenwell D., Luxton F., Venn F., Mills H., Rewbury J., James K., Roberts K., Tonks L., Felmeden D., Taggu W., Summerhayes A., Hughes D., Sutton J., Felmeden L., Khan M., Walker E., Norris L., O'Donohoe L., Mozid A., Dymond H., Lloyd-Jones H., Saunders G., Simmons D., Coles D., Cotterill D., Beech S., Kidd S., Wrigley B., Petkar S., Smallwood A., Jones R., Radford E., Milgate S., Metherell S., Cottam V., Buckley C., Broadley A., Wood D., Allison J., Rennie K., Balian L., Howard L., Pippard L., Board S., Pitt-Kerby T., Pulmonary medicine, Rehabilitation medicine, Internal medicine, Radiology and nuclear medicine, Cardiology, Pulmonary Medicine, General Practice, ACS - Heart failure & arrhythmias, Medical Oncology, Erasmus School of Health Policy & Management, Radiotherapy, Department of Technology and Operations Management, Virology, Erasmus School of Social and Behavioural Sciences, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Tax Law, Epidemiology, Neurosciences, Rheumatology, Erasmus School of Economics, Department of Business-Society Management, Pediatrics, Erasmus MC other, Orthopedics and Sports Medicine, Intensive Care, Department of Marketing Management, Clinical Genetics, Surgery, Econometrics, Research & Education, Radiology & Nuclear Medicine, Neurosurgery, Psychiatry, Department of Psychology, Education and Child Studies, Plastic and Reconstructive Surgery and Hand Surgery, Dermatology, Public Health, Gastroenterology & Hepatology, Erasmus School of Law, and Sociology

Subjects
Registrie, Atrial Fibrillation/drug therapy, Integrated management, Risk Factor, Atrial fibrillation, Clinical complexity, Outcomes, Anticoagulants, Humans, Registries, Risk Factors, Atrial Fibrillation, Stroke, Anticoagulant, General Medicine, Anticoagulants/therapeutic use, Stroke/complications, Outcome, Human
Abstract

Background Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients.

Published
2022
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42. The interplay of saliva, erosion and attrition on enamel and dentine

Author

Aljulayfi, I., O'Toole, S., Healy, M., Sumaidaa, S., Ali, Z., Bartlett, D., and Austin, R.

Subjects
stomatognathic diseases, stomatognathic system, General Dentistry
Abstract

PurposeThis investigation aimed to compare the protective role of saliva against erosion and attrition challenges.MethodPolished enamel and dentine samples (n = 160) were prepared and randomly assigned to either the saliva or saliva-free group (n = 40 enamel and n = 40 dentine/group). Within each subgroup, they were allocated to four subgroups: negative control (deionized water exposure 10 min), erosion (0.3% citric acid 10 min), attrition (120 S of 300 g force), or combined erosion/attrition (0.3% citric acid 10 min then 120 S of 300 g force). Experimental cycles were repeated three times. Data analysis was performed using SPSS.ResultsThe mean and standard deviation (SD) of step heights produced by the attrition and erosion/attrition groups in enamel in the saliva-free group were 5.6 µm (2.4) and 13.4 µm (2.8), respectively, while they were 2.4 µm (3.8) and 12.9 µm (3.5) in the saliva group, with no significant difference between the saliva and saliva-free groups. For dentine, the corresponding step heights were 25.2 µm (5.5) and 35.9 µm (7.9) for the saliva-free group, but 21.8 µm (5.3) and 27.3 µm (6.4) for the saliva group (p < 0.001).ConclusionThere was a trend that saliva decreased wear, but this was only statistically significant for erosion/attrition dentine wear.

Published
2022
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45. Patient preferences for the design of a pharmacy-based colorectal cancer screening program

Author

Alison T. Brenner, Austin R. Waters, Mary Wangen, Catherine Rohweder, Olufeyisayo Odebunmi, Macary Weck Marciniak, Renée M. Ferrari, Stephanie B. Wheeler, and Parth D. Shah

Subjects
Cancer Research, Oncology
Abstract

Purpose To assess preferences for design of a pharmacy-based colorectal cancer (CRC) screening program (PharmFIT™) among screening-eligible adults in the United States (US) and explore the impact of rurality on pharmacy use patterns (e.g., pharmacy type, prescription pick-up preference, service quality rating). Methods We conducted a national online survey of non-institutionalized US adults through panels managed by Qualtrics, a survey research company. A total of 1,045 adults (response rate 62%) completed the survey between March and April 2021. Sampling quotas matched respondents to the 2010 US Census and oversampled rural residents. We assessed pharmacy use patterns by rurality and design preferences for learning about PharmFIT™; receiving a FIT kit from a pharmacy; and completing and returning the FIT kit. Results Pharmacy use patterns varied, with some notable differences across rurality. Rural respondents used local, independently owned pharmacies more than non-rural respondents (20.4%, 6.3%, p p p = 0.02) more frequently than rural participants. Preferences for receiving and returning FITs were associated with pharmacy use patterns: respondents who pick up prescriptions in-person preferred to get their FIT (OR 7.7; 5.3–11.2) and return it in-person at the pharmacy (OR 1.7; 1.1–2.4). Conclusion Pharmacies are highly accessible and could be useful for expanding access to CRC screening services. Local context and pharmacy use patterns should be considered in the design and implementation of PharmFIT™.

Published
2023
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49. Nutrient regulation of the islet epigenome controls adaptive insulin secretion

Author

Matthew Wortham, Fenfen Liu, Austin R. Harrington, Johanna Y. Fleischman, Martina Wallace, Francesca Mulas, Medhavi Mallick, Nicholas K. Vinckier, Benjamin R. Cross, Joshua Chiou, Nisha A. Patel, Yinghui Sui, Carolyn McGrail, Yesl Jun, Gaowei Wang, Ulupi S. Jhala, Roland Schüle, Orian S. Shirihai, Mark O. Huising, Kyle J. Gaulton, Christian M. Metallo, and Maike Sander

Subjects
Cardiovascular and Metabolic Diseases, General Medicine
Abstract

Adaptation of the islet β-cell insulin secretory response to changing insulin demand is critical for blood glucose homeostasis, yet the mechanisms underlying this adaptation are unknown. Here, we have shown that nutrient-stimulated histone acetylation plays a key role in adapting insulin secretion through regulation of genes involved in β-cell nutrient sensing and metabolism. Nutrient regulation of the epigenome occurred at sites occupied by the chromatin-modifying enzyme Lysine-specific demethylase 1 (Lsd1) in islets. β-cell-specific deletion of Lsd1 led to insulin hypersecretion, aberrant expression of nutrient response genes, and histone hyperacetylation. Islets from mice adapted to chronically increased insulin demand exhibited shared epigenetic and transcriptional changes. Moreover, we found that genetic variants associated with type 2 diabetes were enriched at LSD1-bound sites in human islets, suggesting that interpretation of nutrient signals is genetically determined and clinically relevant. Overall, these studies revealed that adaptive insulin secretion involves Lsd1-mediated coupling of nutrient state to regulation of the islet epigenome.

Published
2023
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50. Supplemental Figure S1 from [18F]FluorThanatrace ([18F]FTT) PET Imaging of PARP-Inhibitor Drug-Target Engagement as a Biomarker of Response in Ovarian Cancer, a Pilot Study

Author

Fiona Simpkins, Lilie L. Lin, Robert H. Mach, David A. Mankoff, Robert K. Doot, Gordon B. Mills, Quy Cao, Fang Liu, Shannon M. Lanzo, Lainie P. Martin, Janos L. Tanyi, Nawar A. Latif, Benjamin Ferman, Chia-Ju Hsieh, Drew A. Torigian, Joanna K. Weeks, Sergey Medvedv, Hyoung Kim, Mehran Makvandi, Sarah B. Gitto, and Austin R. Pantel

Abstract

PDX models treated with PARPi therapies.

Published
2023
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