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1. The Type 2 Diabetes Knowledge Portal: An open access genetic resource dedicated to type 2 diabetes and related traits

Author

Costanzo, Maria C, von Grotthuss, Marcin, Massung, Jeffrey, Jang, Dongkeun, Caulkins, Lizz, Koesterer, Ryan, Gilbert, Clint, Welch, Ryan P, Kudtarkar, Parul, Hoang, Quy, Boughton, Andrew P, Singh, Preeti, Sun, Ying, Duby, Marc, Moriondo, Annie, Nguyen, Trang, Smadbeck, Patrick, Alexander, Benjamin R, Brandes, MacKenzie, Carmichael, Mary, Dornbos, Peter, Green, Todd, Huellas-Bruskiewicz, Kenneth C, Ji, Yue, Kluge, Alexandria, McMahon, Aoife C, Mercader, Josep M, Ruebenacker, Oliver, Sengupta, Sebanti, Spalding, Dylan, Taliun, Daniel, Consortium, AMP-T2D, Abecasis, Gonçalo, Akolkar, Beena, Allred, Nicholette D, Altshuler, David, Below, Jennifer E, Bergman, Richard, Beulens, Joline WJ, Blangero, John, Boehnke, Michael, Bokvist, Krister, Bottinger, Erwin, Bowden, Donald, Brosnan, M Julia, Brown, Christopher, Bruskiewicz, Kenneth, Burtt, Noël P, Cebola, Inês, Chambers, John, Chen, Yii-Der Ida, Cherkas, Andriy, Chu, Audrey Y, Clark, Christopher, Claussnitzer, Melina, Cox, Nancy J, Hoed, Marcel den, Dong, Duc, Duggirala, Ravindranath, Dupuis, Josée, Elders, Petra JM, Engreitz, Jesse M, Fauman, Eric, Ferrer, Jorge, Flannick, Jason, Flicek, Paul, Flickinger, Matthew, Florez, Jose C, Fox, Caroline S, Frayling, Timothy M, Frazer, Kelly A, Gaulton, Kyle J, Gloyn, Anna L, Hanis, Craig L, Hanson, Robert, Hattersley, Andrew T, Im, Hae Kyung, Iqbal, Sidra, Jacobs, Suzanne BR, Jang, Dong-Keun, Jordan, Tad, Kamphaus, Tania, Karpe, Fredrik, Keane, Thomas M, Kim, Seung K, Lage, Kasper, Lange, Leslie A, and Lazar, Mitchell

Subjects
Genetics, Diabetes, Human Genome, Metabolic and endocrine, Good Health and Well Being, Humans, Diabetes Mellitus, Type 2, Access to Information, Prospective Studies, Genomics, Phenotype, AMP-T2D Consortium, CMDKP, GWAS, T2DKP, data sharing, diabetes, effector genes, genetic associations, genetic support, genomics, portal, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Endocrinology & Metabolism
Abstract

Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories of these data seek to be disease-agnostic and therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is a public resource of genetic datasets and genomic annotations dedicated to type 2 diabetes (T2D) and related traits. Here, we seek to make the T2DKP more accessible to prospective users and more useful to existing users. First, we evaluate the T2DKP's comprehensiveness by comparing its datasets with those of other repositories. Second, we describe how researchers unfamiliar with human genetic data can begin using and correctly interpreting them via the T2DKP. Third, we describe how existing users can extend their current workflows to use the full suite of tools offered by the T2DKP. We finally discuss the lessons offered by the T2DKP toward the goal of democratizing access to complex disease genetic results.

Published
2023

2. Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing

Author

Chen, Fang, Wang, Xingyan, Jang, Seon-Kyeong, Quach, Bryan C, Weissenkampen, J Dylan, Khunsriraksakul, Chachrit, Yang, Lina, Sauteraud, Renan, Albert, Christine M, Allred, Nicholette DD, Arnett, Donna K, Ashley-Koch, Allison E, Barnes, Kathleen C, Barr, R Graham, Becker, Diane M, Bielak, Lawrence F, Bis, Joshua C, Blangero, John, Boorgula, Meher Preethi, Chasman, Daniel I, Chavan, Sameer, Chen, Yii-Der I, Chuang, Lee-Ming, Correa, Adolfo, Curran, Joanne E, David, Sean P, Fuentes, Lisa de las, Deka, Ranjan, Duggirala, Ravindranath, Faul, Jessica D, Garrett, Melanie E, Gharib, Sina A, Guo, Xiuqing, Hall, Michael E, Hawley, Nicola L, He, Jiang, Hobbs, Brian D, Hokanson, John E, Hsiung, Chao A, Hwang, Shih-Jen, Hyde, Thomas M, Irvin, Marguerite R, Jaffe, Andrew E, Johnson, Eric O, Kaplan, Robert, Kardia, Sharon LR, Kaufman, Joel D, Kelly, Tanika N, Kleinman, Joel E, Kooperberg, Charles, Lee, I-Te, Levy, Daniel, Lutz, Sharon M, Manichaikul, Ani W, Martin, Lisa W, Marx, Olivia, McGarvey, Stephen T, Minster, Ryan L, Moll, Matthew, Moussa, Karine A, Naseri, Take, North, Kari E, Oelsner, Elizabeth C, Peralta, Juan M, Peyser, Patricia A, Psaty, Bruce M, Rafaels, Nicholas, Raffield, Laura M, Reupena, Muagututi’a Sefuiva, Rich, Stephen S, Rotter, Jerome I, Schwartz, David A, Shadyab, Aladdin H, Sheu, Wayne H-H, Sims, Mario, Smith, Jennifer A, Sun, Xiao, Taylor, Kent D, Telen, Marilyn J, Watson, Harold, Weeks, Daniel E, Weir, David R, Yanek, Lisa R, Young, Kendra A, Young, Kristin L, Zhao, Wei, Hancock, Dana B, Jiang, Bibo, Vrieze, Scott, and Liu, Dajiang J

Subjects
Genetics, Tobacco, Drug Abuse (NIDA only), Tobacco Smoke and Health, Substance Misuse, Brain Disorders, Human Genome, Good Health and Well Being, Humans, Transcriptome, Drug Repositioning, Genome-Wide Association Study, Tobacco Use, Biology, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction.

Published
2023

3. Transcriptional analysis of metastatic uveal melanoma survival nominates NRP1 as a therapeutic target

Author

Bao, Riyue, Surriga, Oliver, Olson, Daniel J, Allred, Jacob B, Strand, Carrie A, Zha, Yuanyuan, Carll, Timothy, Labadie, Brian W, Bastos, Bruno R, Butler, Marcus, Hogg, David, Musi, Elgilda, Ambrosini, Grazia, Munster, Pamela, Schwartz, Gary K, and Luke, Jason J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Eye Disease and Disorders of Vision, Orphan Drug, Genetics, Rare Diseases, Cancer, Human Genome, Gene Expression Regulation, Neoplastic, Humans, Melanoma, Neoplasm Metastasis, Skin Neoplasms, Survival Analysis, Transfection, Uveal Neoplasms, gene expression, NRP1, survival, The Cancer Genome Atlas, uveal melanoma, Clinical Sciences, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

Uveal melanoma is a rare form of melanoma with particularly poor outcomes in the metastatic setting. In contrast with cutaneous melanoma, uveal melanoma lacks BRAF mutations and demonstrates very low response rates to immune-checkpoint blockade. Our objectives were to study the transcriptomics of metastatic uveal melanoma with the intent of assessing gene pathways and potential molecular characteristics that might be nominated for further exploration as therapeutic targets. We initially analyzed transcriptional data from The Cancer Genome Atlas suggesting PI3K/mTOR and glycolysis as well as IL6 associating with poor survival. From tumor samples collected in a prospective phase II trial (A091201), we performed a transcriptional analysis of human metastatic uveal melanoma observing a novel role for epithelial-mesenchymal transition associating with survival. Specifically, we nominate and describe initial functional validation of neuropillin-1 from uveal melanoma cells as associated with poor survival and as a mediator of proliferation and migration for uveal melanoma in vitro. These results immediately nominate potential next steps in clinical research for patients with metastatic uveal melanoma.

Published
2021

4. Randomized Phase II Trial and Tumor Mutational Spectrum Analysis from Cabozantinib versus Chemotherapy in Metastatic Uveal Melanoma (Alliance A091201)

Author

Luke, Jason J, Olson, Daniel J, Allred, Jacob B, Strand, Carrie A, Bao, Riyue, Zha, Yuanyuan, Carll, Timothy, Labadie, Brian W, Bastos, Bruno R, Butler, Marcus O, Hogg, David, Munster, Pamela N, and Schwartz, Gary K

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Genetics, Clinical Trials and Supportive Activities, Clinical Research, Cancer, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Aged, Aged, 80 and over, Anilides, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Dacarbazine, Female, Humans, Male, Melanoma, Middle Aged, Mutation, Neoplasm Metastasis, Pyridines, Receptor Protein-Tyrosine Kinases, Temozolomide, Uveal Neoplasms, Exome Sequencing, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeThe surface receptor MET is highly expressed on primary uveal melanoma; MET inhibitors demonstrated early clinical signals of efficacy in slowing uveal melanoma growth. The primary objective of our study was to compare the progression-free survival rate at 4 months (PFS4) of patients with uveal melanoma treated with cabozantinib or chemotherapy.Patients and methodsPatients with metastatic uveal melanoma and RECIST measurable disease were randomized 2:1 to receive either cabozantinib (arm 1) versus temozolomide or dacarbazine (arm 2) with restaging imaging every two cycles. Cross-over from arm 2 to cabozantinib after progression was allowed (arm 2X). Available tumor specimens were analyzed by whole-exome sequencing (WES) and results were correlated with outcome.ResultsForty-six eligible patients were accrued with 31, 15, and 9 in arms 1, 2, and 2X, respectively. Median lines of prior therapy, including hepatic embolization, were two. Rates of PFS4 in arm 1 and arm 2 were 32.3% and 26.7% (P = 0.35), respectively, with median PFS time of 60 and 59 days (P = 0.964; HR = 0.99). Median overall survival (OS) was 6.4 months and 7.3 months (P = 0.580; HR = 1.21), respectively. Grade 3-4 Common Terminology Criteria for Adverse Events were present in 61.3%, 46.7%, and 37.5% in arms 1, 2, and 2X, respectively. WES demonstrated a mean tumor mutational burden of 1.53 mutations/Mb and did not separate OS ≤ or >1 year (P = 0.14). Known mutations were identified by WES and novel mutations were nominated.ConclusionsMET/VEGFR blockade with cabozantinib demonstrated no improvement in PFS but an increase in toxicity relative to temozolomide/dacarbazine in metastatic uveal melanoma.

Published
2020

5. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Kachroo, Priyadarshini, Hecker, Julian, Chawes, Bo L, Ahluwalia, Tarunveer S, Cho, Michael H, Qiao, Dandi, Kelly, Rachel S, Chu, Su H, Virkud, Yamini V, Huang, Mengna, Barnes, Kathleen C, Burchard, Esteban G, Eng, Celeste, Hu, Donglei, Celedón, Juan C, Daya, Michelle, Levin, Albert M, Gui, Hongsheng, Williams, L Keoki, Forno, Erick, Mak, Angel CY, Avila, Lydiana, Soto-Quiros, Manuel E, Cloutier, Michelle M, Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A, Lange, Christoph, Weiss, Scott T, Lasky-Su, Jessica A, National Heart, Lung, Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette Palmer, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, and Das, Sayantan

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Clinical Research, Asthma, Genetics, Pediatric, Biotechnology, Human Genome, Lung, 2.1 Biological and endogenous factors, Respiratory, Adolescent, Adult, Cell Adhesion Molecules, Child, Child, Preschool, Costa Rica, Female, Forced Expiratory Volume, Humans, Interferon Regulatory Factors, Male, Middle Aged, Respiratory Physiological Phenomena, Vital Capacity, Whole Genome Sequencing, Young Adult, airway hyperresponsiveness, asthma, lung function, whole genome sequencing, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundAsthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma.MethodsWGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician's diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes.ResultsA genome-wide significant association was identified between baseline FEV1/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10-8 in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10-6). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV1 (P = 3.3 × 10-3), postbronchodilator (PB) FEV1 (7.3 × 10-3), and PB FEV1/FVC ratio (P = 2.7 × 10-3). The identified baseline FEV1/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR.ConclusionsThese findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

Published
2019

6. Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ.

Author

Ding, Lina, Su, Ying, Fassl, Anne, Hinohara, Kunihiko, Qiu, Xintao, Harper, Nicholas W, Huh, Sung Jin, Bloushtain-Qimron, Noga, Jovanović, Bojana, Ekram, Muhammad, Zi, Xiaoyuan, Hines, William C, Alečković, Maša, Gil Del Alcazar, Carlos, Caulfield, Ryan J, Bonal, Dennis M, Nguyen, Quang-De, Merino, Vanessa F, Choudhury, Sibgat, Ethington, Gabrielle, Panos, Laura, Grant, Michael, Herlihy, William, Au, Alfred, Rosson, Gedge D, Argani, Pedram, Richardson, Andrea L, Dillon, Deborah, Allred, D Craig, Babski, Kirsten, Kim, Elizabeth Min Hui, McDonnell, Charles H, Wagner, Jon, Rowberry, Ron, Bobolis, Kristie, Kleer, Celina G, Hwang, E Shelley, Blum, Joanne L, Cristea, Simona, Sicinski, Piotr, Fan, Rong, Long, Henry W, Sukumar, Saraswati, Park, So Yeon, Garber, Judy E, Bissell, Mina, Yao, Jun, and Polyak, Kornelia

Subjects
Cell Line, Tumor, Animals, Humans, Mice, Carcinoma, Ductal, Breast, Tumor Suppressor Proteins, BRCA1 Protein, BRCA2 Protein, Transcription Factors, Fluorescent Antibody Technique, Immunohistochemistry, Cell Proliferation, Mutation, Germ-Line Mutation, Female, T Cell Transcription Factor 1, Cell Line, Tumor, Carcinoma, Ductal, Breast, Breast Cancer, Cancer, Prevention, Genetics, 2.1 Biological and endogenous factors, MD Multidisciplinary
Abstract

Myoepithelial cells play key roles in normal mammary gland development and in limiting pre-invasive to invasive breast tumor progression, yet their differentiation and perturbation in ductal carcinoma in situ (DCIS) are poorly understood. Here, we investigated myoepithelial cells in normal breast tissues of BRCA1 and BRCA2 germline mutation carriers and in non-carrier controls, and in sporadic DCIS. We found that in the normal breast of non-carriers, myoepithelial cells frequently co-express the p63 and TCF7 transcription factors and that p63 and TCF7 show overlapping chromatin peaks associated with differentiated myoepithelium-specific genes. In contrast, in normal breast tissues of BRCA1 mutation carriers the frequency of p63+TCF7+ myoepithelial cells is significantly decreased and p63 and TCF7 chromatin peaks do not overlap. These myoepithelial perturbations in normal breast tissues of BRCA1 germline mutation carriers may play a role in their higher risk of breast cancer. The fraction of p63+TCF7+ myoepithelial cells is also significantly decreased in DCIS, which may be associated with invasive progression.

Published
2019

7. Whole genome sequence analyses of brain imaging measures in the Framingham Study

Author

Sarnowski, Chloé, Satizabal, Claudia L, DeCarli, Charles, Pitsillides, Achilleas N, Cupples, L Adrienne, Vasan, Ramachandran S, Wilson, James G, Bis, Joshua C, Fornage, Myriam, Beiser, Alexa S, DeStefano, Anita L, Dupuis, Josée, Seshadri, Sudha, Arnett, Donna K, Becker, Diane, Bis, Joshua, Boerwinkle, Eric, Bowers, Michael, Bressler, Jan, Correa, Adolfo, DeStefano, Anita, Ding, Jingzhong ding, Fardo, David, Lugo, Alex Garcia, Glahn, David, Gonzalez, Hector, Hayden, Kathleen, Heckbert, Susan, Hoth, Karin, Hughes, Timothy, Jaquish, Cashell, Jian, Xueqiu, Knowles, Emma, Launer, Lenore, Lin, Honghuang, Longstreth, Will, Mayeux, Richard, Misra, Biswapriya, Mosley, Thomas, Nyquist, Paul, Olivier, Michael, Peprah, Emmanuel, Psaty, Bruce, Purcell, Shaun, Rotter, Jerome, Satizabal, Claudia, Schellenberg, Gerard, Simino, Jeannette, Smith, Jennifer, Smoller, Sylvia, Snively, Beverly, Sokolow, Sophie, Wehr, Kate, Yanek, Lisa, Yang, Qiong, Namiko, Abe, Goncalo, Abecasis, Christine, Albert, Nicholette (Nichole) Palmer, Allred, Laura, Almasy, Alvaro, Alonso, Seth, Ament, Peter, Anderson, Pramod, Anugu, Deborah, Applebaum-Bowden, Dan, Arking, Donna K, Arnett, Allison, Ashley-Koch, Stella, Aslibekyan, Tim, Assimes, Paul, Auer, Dimitrios, Avramopoulos, John, Barnard, Kathleen, Barnes, Graham, Barr R, Emily, Barron-Casella, Terri, Beaty, Diane, Becker, Lewis, Becker, Rebecca, Beer, Ferdouse, Begum, Amber, Beitelshees, Emelia, Benjamin, Marcos, Bezerra, Larry, Bielak, Joshua, Bis, Thomas, Blackwell, John, Blangero, Eric, Boerwinkle, Ingrid, Borecki, Russell, Bowler, Jennifer, Brody, Ulrich, Broeckel, Jai, Broome, Karen, Bunting, Esteban, Burchard, and Jonathan, Cardwell

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Genetics, Biotechnology, Human Genome, Aging, Brain Disorders, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Neurological, Good Health and Well Being, Aged, Brain, Female, Genetic Variation, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Male, Massachusetts, Middle Aged, Organ Size, Phenotype, Prospective Studies, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Neurocognitive Working Group, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveWe sought to identify rare variants influencing brain imaging phenotypes in the Framingham Heart Study by performing whole genome sequence association analyses within the Trans-Omics for Precision Medicine Program.MethodsWe performed association analyses of cerebral and hippocampal volumes and white matter hyperintensity (WMH) in up to 2,180 individuals by testing the association of rank-normalized residuals from mixed-effect linear regression models adjusted for sex, age, and total intracranial volume with individual variants while accounting for familial relatedness. We conducted gene-based tests for rare variants using (1) a sliding-window approach, (2) a selection of functional exonic variants, or (3) all variants.ResultsWe detected new loci in 1p21 for cerebral volume (minor allele frequency [MAF] 0.005, p = 10-8) and in 16q23 for hippocampal volume (MAF 0.05, p = 2.7 × 10-8). Previously identified associations in 12q24 for hippocampal volume (rs7294919, p = 4.4 × 10-4) and in 17q25 for WMH (rs7214628, p = 2.0 × 10-3) were confirmed. Gene-based tests detected associations (p ≤ 2.3 × 10-6) in new loci for cerebral (5q13, 8p12, 9q31, 13q12-q13, 15q24, 17q12, 19q13) and hippocampal volumes (2p12) and WMH (3q13, 4p15) including Alzheimer disease- (UNC5D) and Parkinson disease-associated genes (GBA). Pathway analyses evidenced enrichment of associated genes in immunity, inflammation, and Alzheimer disease and Parkinson disease pathways.ConclusionsWhole genome sequence-wide search reveals intriguing new loci associated with brain measures. Replication of novel loci is needed to confirm these findings.

Published
2018

8. Validation of the Parental Facilitation of Mastery Scale–II

Author

Zalta, Alyson K, Allred, Kelly M, Jayawickreme, Eranda, Blackie, Laura ER, and Chambless, Dianne L

Subjects
Social and Personality Psychology, Psychology, Behavioral and Social Science, Clinical Research, Adolescent, Adult, Aged, Female, Humans, Internal-External Control, Male, Mental Disorders, Middle Aged, Parenting, Parents, Personal Satisfaction, Psychiatric Status Rating Scales, Psychometrics, Reproducibility of Results, Self Efficacy, Surveys and Questionnaires, Young Adult, parenting, overprotection, challenge, mastery, self-efficacy, Cognitive Sciences, Clinical Psychology, Clinical sciences, Applied and developmental psychology, Clinical and health psychology
Abstract

ObjectiveTo develop a more reliable and comprehensive version of the Parental Facilitation of Mastery Scale (PFMS) METHOD: In Study 1, 387 undergraduates completed an expanded PFMS (PFMS-II) and measures of parenting, perceived control, responses to early life challenges, and psychopathology. In Study 2, 182 trauma-exposed community participants completed the PFMS-II and measures of perceived control, psychopathology, and well-being RESULTS: In Study 1, exploratory factor analysis of the PFMS-II revealed two factors. These factors replicated in Study 2; one item was removed to achieve measurement invariance across race. The final PFMS-II comprised a 10-item overprotection scale and a 7-item challenge scale. In both samples, this measure demonstrated good convergent and discriminant validity and was more reliable than the original PFMS. Parental challenge was a unique predictor of perceived control in both samples CONCLUSION: The PFMS-II is a valid measure of important parenting behaviors not fully captured in other measures.

Published
2017

9. Management of Bacteriuria in Veterans Affairs Hospitals

Author

Spivak, Emily S, Burk, Muriel, Zhang, Rongping, Jones, Makoto M, Neuhauser, Melinda M, Goetz, Matthew Bidwell, Cunningham, Francesca E, Group, for the Management of Urinary Tract Infections Medication Use Evaluation, Wright, Jason, Johns, Scott, Ma, Ariel, Casavant, Jonathan, Haley, James A, Cartmell, Bryan, Dahl, Jaela, Mercurio, Amanda, Haake, Ashley, Muthusi, Cynthia, Phabmixay, Jenny, Hines, Edward, Chew, Alexander B, Patel, Ursula, Duquaine, Susan, Kuoma, Marcus, Mang, Norman, Aylward, Andrea, Harris, Jessica, O’Brien, Jessica, Dietz, Jessica, Curtin, Rebecca, Fisher, Ann, Manganiello, Lauren, O’Donnell, Jill, Surdy, Michael, Morabito, Brianna, Page, Theresa, Pardo, Joseph, McQuillan, Amanda, Clare, Danielle, Deyle, Tessa, Bodine, Rita, Kuyrkendall, Evan, Guyear, Jamie, Witt, Lauri, Hobbs, Deborah, Scott, Ashley, Swanson, Marci, MacKay, Kimberly T, Wilbur, Eileen, Butler, Phalyn, Orlando, Patricia, Arnold, Joshua, Loesch, Erin, Fioravanti, Nicole, Tate, Victoria, Allred, Carol, Cole, Jennifer, Walker, Michelle, Young, Lisa, Peters, James J, Kish, Troy D, Noble, Kelcey, Woelfel, Kirsten, Foral, Pamela, Carrasquillo, Mara, and Gauthier, Timothy P

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Hematology, Urologic Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Aged, Aged, 80 and over, Anti-Bacterial Agents, Asymptomatic Infections, Bacteriuria, Catheter-Related Infections, Cause of Death, Clostridioides difficile, Clostridium Infections, Cystitis, Female, Fluoroquinolones, Hospitals, Veterans, Humans, Male, Middle Aged, Patient Readmission, Pyelonephritis, Urinary Catheters, urinary tract infection, antimicrobial stewardship, Management of Urinary Tract Infections Medication Use Evaluation Group, Management of Urinary Tract Infections Medication Use Evaluation Group, Biological Sciences, Medical and Health Sciences, Microbiology, Clinical sciences
Abstract

BackgroundBacteriuria contributes to antibiotic overuse through treatment of asymptomatic bacteriuria (ASB) and long durations of therapy for symptomatic urinary tract infections (UTIs), yet large-scale evaluations of bacteriuria management among inpatients are lacking.MethodsInpatients with bacteriuria were classified as asymptomatic or symptomatic based on established criteria applied to data collected by manual chart review. We examined frequency of treatment of ASB, factors associated with treatment of ASB, durations of therapy, and frequency of complications including Clostridium difficile infection, readmission, and all-cause mortality within 28 days of discharge.ResultsAmong 2225 episodes of bacteriuria, 64% were classified as ASB. After excluding patients with non-UTI indications for antibiotics, 72% of patients with ASB received antibiotics. When evaluating only patients not meeting SIRS criteria, 68% of patients with ASB received antibiotics. The mean (±SD) days of antibiotic therapy for ASB, cystitis, CA-UTI and pyelonephritis were 10.0 (4.5), 11.4 (4.7), 12.0 (6.1), and 13.6 (5.3), respectively. In sum, 14% of patients with ASB were treated for greater than 14 days, and fluoroquinolones were the most commonly used empiric antibiotic for ASB [245/691 (35%)]. Complications were rare but more common among patients with ASB treated with antibiotics.ConclusionsThe majority of bacteriuria among inpatient veterans is due to ASB with high rates of treatment of ASB and prolonged durations of therapy for ASB and symptomatic UTIs.

Published
2017

10. Patients with ALS show highly correlated progression rates in left and right limb muscles

Author

Rushton, David J, Andres, Patricia L, Allred, Peggy, Baloh, Robert H, and Svendsen, Clive N

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Neurodegenerative, Clinical Research, Rare Diseases, ALS, Brain Disorders, Neurological, Musculoskeletal, Adult, Amyotrophic Lateral Sclerosis, Disease Progression, Extremities, Follow-Up Studies, Humans, Models, Statistical, Muscle Strength, Muscle, Skeletal, Neurologic Examination, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveAmyotrophic lateral sclerosis (ALS) progresses at different rates between patients, making clinical trial design difficult and dependent on large cohorts of patients. Currently, there are few data showing whether the left and right limbs progress at the same or different rates. This study addresses rates of decline in specific muscle groups of patients with ALS and assesses whether there is a relationship between left and right muscles in the same patient, regardless of overall progression.MethodsA large cohort of patients was used to assess decline in muscle strength in right and left limbs over time using 2 different methods: The Tufts Quantitative Neuromuscular Exam and Accurate Test of Limb Isometric Strength protocol. Then advanced linear regression statistical methods were applied to assess progression rates in each limb.ResultsThis report shows that linearized progression models can predict general slopes of decline with good accuracy. Critically, the data demonstrate that while overall decline is variable, there is a high degree of correlation between left and right muscle decline in ALS. This implies that irrespective of which muscle starts declining soonest or latest, their rates of decline following onset are more consistent.ConclusionsFirst, this study demonstrates a high degree of power when using unilateral treatment approaches to detect a slowing in disease progression in smaller groups of patients, thus allowing for paired statistical tests. These findings will be useful in transplantation trials that use muscle decline to track disease progression in ALS. Second, these findings discuss methods, such as tactical selection of muscle groups, which can improve the power efficiency of all ALS clinical trials.

Published
2017

11. Ki67 Proliferation Index as a Tool for Chemotherapy Decisions During and After Neoadjuvant Aromatase Inhibitor Treatment of Breast Cancer: Results From the American College of Surgeons Oncology Group Z1031 Trial (Alliance)

Author

Ellis, Matthew J, Suman, Vera J, Hoog, Jeremy, Goncalves, Rodrigo, Sanati, Souzan, Creighton, Chad J, DeSchryver, Katherine, Crouch, Erika, Brink, Amy, Watson, Mark, Luo, Jingqin, Tao, Yu, Barnes, Michael, Dowsett, Mitchell, Budd, G Thomas, Winer, Eric, Silverman, Paula, Esserman, Laura, Carey, Lisa, X., Cynthia, Unzeitig, Gary, Pluard, Timothy, Whitworth, Pat, Babiera, Gildy, Guenther, J Michael, Dayao, Zoneddy, Ota, David, Leitch, Marilyn, Olson, John A, Allred, D Craig, and Hunt, Kelly

Subjects
Cancer, Aging, Estrogen, Clinical Trials and Supportive Activities, Clinical Research, Breast Cancer, Development of treatments and therapeutic interventions, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, 5.1 Pharmaceuticals, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Aged, Anastrozole, Androstadienes, Antineoplastic Combined Chemotherapy Protocols, Aromatase Inhibitors, Breast Neoplasms, Clinical Decision-Making, Female, Follow-Up Studies, Humans, Ki-67 Antigen, Letrozole, Middle Aged, Mitotic Index, Neoadjuvant Therapy, Neoplasm Metastasis, Neoplasm Recurrence, Local, Neoplasm Staging, Nitriles, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Receptors, Estrogen, Receptors, Progesterone, Survival Rate, Transcriptome, Triazoles, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole. For the trial ACOSOG Z1031B, the protocol was amended to include a tumor Ki67 determination after 2 to 4 weeks of AI. If the Ki67 was > 10%, patients were switched to neoadjuvant chemotherapy. A pCR rate of > 20% was the predefined efficacy threshold. In patients who completed neoadjuvant AI, stratified Cox modeling was used to assess whether time to recurrence differed by PEPI = 0 score (T1 or T2, N0, Ki67 < 2.7%, ER Allred > 2) versus PEPI > 0 disease. Results Only two of the 35 patients in ACOSOG Z1031B who were switched to neoadjuvant chemotherapy experienced a pCR (5.7%; 95% CI, 0.7% to 19.1%). After 5.5 years of median follow-up, four (3.7%) of the 109 patients with a PEPI = 0 score relapsed versus 49 (14.4%) of 341 of patients with PEPI > 0 (recurrence hazard ratio [PEPI = 0 v PEPI > 0], 0.27; P = .014; 95% CI, 0.092 to 0.764). Conclusion Chemotherapy efficacy was lower than expected in ER-positive tumors exhibiting AI-resistant proliferation. The optimal therapy for these patients should be further investigated. For patients with PEPI = 0 disease, the relapse risk over 5 years was only 3.6% without chemotherapy, supporting the study of adjuvant endocrine monotherapy in this group. These Ki67 and PEPI triage approaches are being definitively studied in the ALTERNATE trial (Alternate Approaches for Clinical Stage II or III Estrogen Receptor Positive Breast Cancer Neoadjuvant Treatment in Postmenopausal Women: A Phase III Study; clinical trial information: NCT01953588).

Published
2017

12. Defining SOD1 ALS natural history to guide therapeutic clinical trial design

Author

Bali, Taha, Self, Wade, Liu, Jingxia, Siddique, Teepu, Wang, Leo H, Bird, Thomas D, Ratti, Elena, Atassi, Nazem, Boylan, Kevin B, Glass, Jonathan D, Maragakis, Nicholas J, Caress, James B, McCluskey, Leo F, Appel, Stanley H, Wymer, James P, Gibson, Summer, Zinman, Lorne, Mozaffar, Tahseen, Callaghan, Brian, McVey, April L, Jockel-Balsarotti, Jennifer, Allred, Peggy, Fisher, Elena R, Lopate, Glenn, Pestronk, Alan, Cudkowicz, Merit E, and Miller, Timothy M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Neurosciences, ALS, Rare Diseases, Clinical Research, Neurodegenerative, Clinical Trials and Supportive Activities, Adult, Age of Onset, Amyotrophic Lateral Sclerosis, Clinical Trials as Topic, Disease Progression, Humans, Middle Aged, Mutation, Research Design, Retrospective Studies, Superoxide Dismutase, Vital Capacity, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ImportanceUnderstanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALSSOD1) will provide key information for optimising clinical trials in this patient population.ObjectiveTo establish an updated natural history of ALSSOD1.Design, setting and participantsRetrospective cohort study from 15 medical centres in North America evaluated records from 175 patients with ALS with genetically confirmed SOD1 mutations, cared for after the year 2000.Main outcomes and measuresAge of onset, survival, ALS Functional Rating Scale (ALS-FRS) scores and respiratory function were analysed. Patients with the A4V (Ala-Val) SOD1 mutation (SOD1A4V), the largest mutation population in North America with an aggressive disease progression, were distinguished from other SOD1 mutation patients (SOD1non-A4V) for analysis.ResultsMean age of disease onset was 49.7±12.3 years (mean±SD) for all SOD1 patients, with no statistical significance between SOD1A4V and SOD1non-A4V (p=0.72, Kruskal-Wallis). Total SOD1 patient median survival was 2.7 years. Mean disease duration for all SOD1 was 4.6±6.0 and 1.4±0.7 years for SOD1A4V. SOD1A4V survival probability (median survival 1.2 years) was significantly decreased compared with SOD1non-A4V (median survival 6.8 years; p

Published
2017

13. Editor’s Highlight: Microbial-Derived 1,4-Dihydroxy-2-naphthoic Acid and Related Compounds as Aryl Hydrocarbon Receptor Agonists/Antagonists: Structure–Activity Relationships and Receptor Modeling

Author

Cheng, Yating, Jin, Un-Ho, Davidson, Laurie A, Chapkin, Robert S, Jayaraman, Arul, Tamamis, Phanourios, Orr, Asuka, Allred, Clint, Denison, Michael S, Soshilov, Anatoly, Weaver, Evelyn, and Safe, Stephen

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Digestive Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Cancer, Animals, Caco-2 Cells, Cell Line, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1B1, Guinea Pigs, Humans, Mice, Models, Theoretical, Naphthalenes, Naphthols, Polychlorinated Dibenzodioxins, Receptors, Aryl Hydrocarbon, Structure-Activity Relationship, 1, 4-DHNA, structure-activity, Ah receptor, agonists, antagonists, antagonists., Toxicology, Pharmacology and pharmaceutical sciences
Abstract

1,4-Dihydroxy-2-naphthoic acid (1,4-DHNA) is a bacterial-derived metabolite that binds the aryl hydrocarbon receptor (AhR) and exhibits anti-inflammatory activity in the gut. The structure-dependent AhR activity of hydroxyl/carboxy-substituted naphthoic acids (NAs) was determined in young adult mouse colonic (YAMC) cells and human Caco2 colon cancer cells using CYP1A1/CYP1B1 mRNAs as Ah-responsive genes. Compounds used in this study include 1,4-, 3,5-, and 3,7-DHNA, 1,4-dimethoxy-2-naphthoic acid (1,4-DMNA), 1- and 4-hydroxy-2-naphthoic acid (1-HNA, 4-HNA), 1- and 2-naphthoic acid (1-NA, 2-NA), and 1- and 2-naphthol (1-NOH, 2-NOH). 1,4-DHNA was the most potent compound among hydroxyl/carboxy naphthalene derivatives, and the fold induction response for CYP1A1 and CYP1B1 was similar to that observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in YAMC and Caco2 cells. 1- and 4-HNA were less potent than 1,4-DHNA but induced maximal (TCDD-like) response for CYP1B1 (both cell lines) and CYP1A1 (Caco2 cells). With the exception of 1- and 2-NA, all compounds significantly induced Cyp1b1 in YAMC cells and these responses were not observed in AhR-deficient YAMC cells generated using CRISPR/Cas9 technology. In addition, we also observed that 1- and 2-NOH (and 1,4-DHNA) were weak AhR agonists, and 1- and 2-NOH also exhibited partial AhR antagonist activity. Structure-activity relationship studies for CYP1A1 but not CYP1B1 were similar in both cell lines, and CYP1A1 induction required one or both 1,4-dihydroxy substituents and activity was significantly enhanced by the 2-carboxyl group. We also used computational analysis to show that 1,4-DHNA and TCDD share similar interactions within the AhR binding pocket and differ primarily due to the negatively charged group of 1,4-DHNA.

Published
2017

14. Disposal of iron by a mutant form of lipocalin 2.

Author

Barasch, Jonathan, Hollmen, Maria, Deng, Rong, Hod, Eldad A, Rupert, Peter B, Abergel, Rebecca J, Allred, Benjamin E, Xu, Katherine, Darrah, Shaun F, Tekabe, Yared, Perlstein, Alan, Wax, Rebecca, Bruck, Efrat, Stauber, Jacob, Corbin, Kaitlyn A, Buchen, Charles, Slavkovich, Vesna, Graziano, Joseph, Spitalnik, Steven L, Bao, Guanhu, Strong, Roland K, and Qiu, Andong

Subjects
Kidney, Animals, Mice, Transgenic, Humans, Mice, Iron Overload, Disease Models, Animal, Inflammation, Iron, Transferrin, Siderophores, Iron Chelating Agents, Ligands, Protein Binding, Oxidation-Reduction, Mutation, Lipocalin-2, Transgenic, Disease Models, Animal, Kidney Disease, Prevention
Abstract

Iron overload damages many organs. Unfortunately, therapeutic iron chelators also have undesired toxicity and may deliver iron to microbes. Here we show that a mutant form (K3Cys) of endogenous lipocalin 2 (LCN2) is filtered by the kidney but can bypass sites of megalin-dependent recapture, resulting in urinary excretion. Because K3Cys maintains recognition of its cognate ligand, the iron siderophore enterochelin, this protein can capture and transport iron even in the acidic conditions of urine. Mutant LCN2 strips iron from transferrin and citrate, and delivers it into the urine. In addition, it removes iron from iron overloaded mice, including models of acquired (iron-dextran or stored red blood cells) and primary (Hfe-/-) iron overload. In each case, the mutants reduce redox activity typical of non-transferrin-bound iron. In summary, we present a non-toxic strategy for iron chelation and urinary elimination, based on manipulating an endogenous protein:siderophore:iron clearance pathway.

Published
2016

15. Catechol Siderophore Transport by Vibrio cholerae

Author

Wyckoff, Elizabeth E, Allred, Benjamin E, Raymond, Kenneth N, and Payne, Shelley M

Subjects
Foodborne Illness, Emerging Infectious Diseases, Vaccine Related, Prevention, Biodefense, Digestive Diseases, Infectious Diseases, 2.2 Factors relating to the physical environment, Aetiology, Infection, Good Health and Well Being, Animals, Bacterial Outer Membrane Proteins, Bacterial Proteins, Biological Transport, Catechols, Enterobactin, Gene Expression Regulation, Bacterial, Humans, Molecular Structure, Receptors, Cell Surface, Siderophores, Vibrio cholerae, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Microbiology
Abstract

UnlabelledSiderophores, small iron-binding molecules secreted by many microbial species, capture environmental iron for transport back into the cell. Vibrio cholerae synthesizes and uses the catechol siderophore vibriobactin and also uses siderophores secreted by other species, including enterobactin produced by Escherichia coli. E. coli secretes both canonical cyclic enterobactin and linear enterobactin derivatives likely derived from its cleavage by the enterobactin esterase Fes. We show here that V. cholerae does not use cyclic enterobactin but instead uses its linear derivatives. V. cholerae lacked both a receptor for efficient transport of cyclic enterobactin and enterobactin esterase to promote removal of iron from the ferrisiderophore complex. To further characterize the transport of catechol siderophores, we show that the linear enterobactin derivatives were transported into V. cholerae by either of the catechol siderophore receptors IrgA and VctA, which also transported the synthetic siderophore MECAM [1,3,5-N,N',N″-tris-(2,3-dihydroxybenzoyl)-triaminomethylbenzene]. Vibriobactin is transported via the additional catechol siderophore receptor ViuA, while the Vibrio fluvialis siderophore fluvibactin was transported by all three catechol receptors. ViuB, a putative V. cholerae siderophore-interacting protein (SIP), functionally substituted for the E. coli ferric reductase YqjH, which promotes the release of iron from the siderophore in the bacterial cytoplasm. In V. cholerae, ViuB was required for the use of vibriobactin but was not required for the use of MECAM, fluvibactin, ferrichrome, or the linear derivatives of enterobactin. This suggests the presence of another protein in V. cholerae capable of promoting the release of iron from these siderophores.ImportanceVibrio cholerae is a major human pathogen and also serves as a model for the Vibrionaceae, which include other serious human and fish pathogens. The ability of these species to persist and acquire essential nutrients, including iron, in the environment is epidemiologically important but not well understood. In this work, we characterize the ability of V. cholerae to acquire iron by using siderophores produced by other organisms. We resolve confusion in the literature regarding its ability to use the Escherichia coli siderophore enterobactin and identify the receptor and TonB system used for the transport of several siderophores. The use of some siderophores did not require the ferric reductase ViuB, suggesting that an uncharacterized ferric reductase is present in V. cholerae.

Published
2015

16. Siderocalin-mediated recognition, sensitization, and cellular uptake of actinides

Author

Allred, Benjamin E, Rupert, Peter B, Gauny, Stacey S, An, Dahlia D, Ralston, Corie Y, Sturzbecher-Hoehne, Manuel, Strong, Roland K, and Abergel, Rebecca J

Subjects
Biochemistry and Cell Biology, Inorganic Chemistry, Chemical Sciences, Biological Sciences, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Actinoid Series Elements, Carrier Proteins, Chelating Agents, Crystallography, X-Ray, Humans, Hydrogen-Ion Concentration, Ions, Kinetics, Lanthanoid Series Elements, Ligands, Lipocalin-2, Luminescence, Metals, Molecular Conformation, Nuclear Power Plants, Photochemistry, Protein Binding, Proteins, Radioactive Hazard Release, Spectrophotometry, Static Electricity, X-Ray Diffraction, actinide transport, siderocalin, protein crystallography, luminescence spectroscopy, antenna effect
Abstract

Synthetic radionuclides, such as the transuranic actinides plutonium, americium, and curium, present severe health threats as contaminants, and understanding the scope of the biochemical interactions involved in actinide transport is instrumental in managing human contamination. Here we show that siderocalin, a mammalian siderophore-binding protein from the lipocalin family, specifically binds lanthanide and actinide complexes through molecular recognition of the ligands chelating the metal ions. Using crystallography, we structurally characterized the resulting siderocalin-transuranic actinide complexes, providing unprecedented insights into the biological coordination of heavy radioelements. In controlled in vitro assays, we found that intracellular plutonium uptake can occur through siderocalin-mediated endocytosis. We also demonstrated that siderocalin can act as a synergistic antenna to sensitize the luminescence of trivalent lanthanide and actinide ions in ternary protein-ligand complexes, dramatically increasing the brightness and efficiency of intramolecular energy transfer processes that give rise to metal luminescence. Our results identify siderocalin as a potential player in the biological trafficking of f elements, but through a secondary ligand-based metal sequestration mechanism. Beyond elucidating contamination pathways, this work is a starting point for the design of two-stage biomimetic platforms for photoluminescence, separation, and transport applications.

Published
2015

17. The Psychological Science Accelerator’s COVID-19 rapid-response dataset

Author

Buchanan, Erin M., Lewis, Savannah C., Paris, Bastien, Forscher, Patrick S., Pavlacic, Jeffrey M., Beshears, Julie E., Drexler, Shira Meir, Gourdon-Kanhukamwe, Amélie, Mallik, Peter R., Silan, Miguel Alejandro A., Miller, Jeremy K., IJzerman, Hans, Moshontz, Hannah, Beaudry, Jennifer L., Suchow, Jordan W., Chartier, Christopher R., Coles, Nicholas A., Sharifian, Mohammad Hasan, Todsen, Anna Louise, Levitan, Carmel A., Azevedo, Flávio, Legate, Nicole, Heller, Blake, Rothman, Alexander J., Dorison, Charles A., Gill, Brian P., Wang, Ke, Rees, Vaughan W., Gibbs, Nancy, Goldenberg, Amit, Thi Nguyen, Thuy vy, Gross, James J., Kaminski, Gwenaêl, von Bastian, Claudia C., Paruzel-Czachura, Mariola, Mosannenzadeh, Farnaz, Azouaghe, Soufian, Bran, Alexandre, Ruiz-Fernandez, Susana, Santos, Anabela Caetano, Reggev, Niv, Zickfeld, Janis H., Akkas, Handan, Pantazi, Myrto, Ropovik, Ivan, Korbmacher, Max, Arriaga, Patrícia, Gjoneska, Biljana, Warmelink, Lara, Alves, Sara G., de Holanda Coelho, Gabriel Lins, Stieger, Stefan, Schei, Vidar, Hanel, Paul H.P., Szaszi, Barnabas, Fedotov, Maksim, Antfolk, Jan, Marcu, Gabriela Mariana, Schrötter, Jana, Kunst, Jonas R., Geiger, Sandra J., Adetula, Adeyemi, Kocalar, Halil Emre, Kielińska, Julita, Kačmár, Pavol, Bokkour, Ahmed, Galindo-Caballero, Oscar J., Djamai, Ikhlas, Pöntinen, Sara Johanna, Agesin, Bamikole Emmanuel, Jernsäther, Teodor, Urooj, Anum, Rachev, Nikolay R., Koptjevskaja-Tamm, Maria, Kurfalı, Murathan, Pit, Ilse L., Li, Ranran, Çoksan, Sami, Dubrov, Dmitrii, Paltrow, Tamar Elise, Baník, Gabriel, Korobova, Tatiana, Studzinska, Anna, Jiang, Xiaoming, Aruta, John Jamir Benzon R., Vintr, Jáchym, Chiu, Faith, Kaliska, Lada, Berkessel, Jana B., Tümer, Murat, Morales-Izquierdo, Sara, Chuan-Peng, Hu, Vezirian, Kevin, Rosa, Anna Dalla, Bialobrzeska, Olga, Vasilev, Martin R., Beitner, Julia, Kácha, Ondřej, Žuro, Barbara, Westerlund, Minja, Nedelcheva-Datsova, Mina, Findor, Andrej, Krupić, Dajana, Kowal, Marta, Askelund, Adrian Dahl, Pourafshari, Razieh, Đorđević, Jasna Milošević, Schmidt, Nadya Daniela, Baklanova, Ekaterina, Szala, Anna, Zakharov, Ilya, Vranka, Marek A., Ihaya, Keiko, Grano, Caterina, Cellini, Nicola, Białek, Michał, Anton-Boicuk, Lisa, Dalgar, Ilker, Adıgüzel, Arca, Verharen, Jeroen P.H., Maturan, Princess Lovella G., Kassianos, Angelos P., Oliveira, Raquel, Čadek, Martin, Adoric, Vera Cubela, Özdoğru, Asil Ali, Sverdrup, Therese E., Aczel, Balazs, Zambrano, Danilo, Ahmed, Afroja, Tamnes, Christian K., Yamada, Yuki, Volz, Leonhard, Sunami, Naoyuki, Suter, Lilian, Vieira, Luc, Groyecka-Bernard, Agata, Kamburidis, Julia Arhondis, Reips, Ulf Dietrich, Harutyunyan, Mikayel, Adetula, Gabriel Agboola, Allred, Tara Bulut, Barzykowski, Krystian, Antazo, Benedict G., Zsido, Andras N., Šakan, Dušana Dušan, Cyrus-Lai, Wilson, Ahlgren, Lina Pernilla, Hruška, Matej, Vega, Diego, Manunta, Efisio, Mokady, Aviv, Capizzi, Mariagrazia, Martončik, Marcel, Say, Nicolas, Filip, Katarzyna, Vilar, Roosevelt, Staniaszek, Karolina, Vdovic, Milica, Adamkovic, Matus, Johannes, Niklas, Hajdu, Nandor, Cohen, Noga, Overkott, Clara, Krupić, Dino, Hubena, Barbora, Nilsonne, Gustav, Mioni, Giovanna, Solorzano, Claudio Singh, Ishii, Tatsunori, Chen, Zhang, Kushnir, Elizaveta, Karaarslan, Cemre, Ribeiro, Rafael R., Khaoudi, Ahmed, Kossowska, Małgorzata, Bavolar, Jozef, Hoyer, Karlijn, Roczniewska, Marta, Karababa, Alper, Becker, Maja, Monteiro, Renan P., Kunisato, Yoshihiko, Metin-Orta, Irem, Adamus, Sylwia, Kozma, Luca, Czarnek, Gabriela, Domurat, Artur, Štrukelj, Eva, Alvarez, Daniela Serrato, Parzuchowski, Michal, Massoni, Sébastien, Czamanski-Cohen, Johanna, Pronizius, Ekaterina, Muchembled, Fany, van Schie, Kevin, Saçaklı, Aslı, Hristova, Evgeniya, Kuzminska, Anna O., Charyate, Abdelilah, Bijlstra, Gijsbert, Afhami, Reza, Majeed, Nadyanna M., Musser, Erica D., Sirota, Miroslav, Ross, Robert M., Yeung, Siu Kit, Papadatou-Pastou, Marietta, Foroni, Francesco, Almeida, Inês A.T., Grigoryev, Dmitry, Lewis, David M.G., Holford, Dawn L., Janssen, Steve M.J., Tatachari, Srinivasan, Batres, Carlota, Olofsson, Jonas K., Daches, Shimrit, Belaus, Anabel, Pfuhl, Gerit, Corral-Frias, Nadia Sarai, Sousa, Daniela, Röer, Jan Philipp, Isager, Peder Mortvedt, Godbersen, Hendrik, Walczak, Radoslaw B., Van Doren, Natalia, Ren, Dongning, Gill, Tripat, Voracek, Martin, DeBruine, Lisa M., Anne, Michele, Očovaj, Sanja Batić, Thomas, Andrew G., Arvanitis, Alexios, Ostermann, Thomas, Wolfe, Kelly, Arinze, Nwadiogo Chisom, Bundt, Carsten, Lamm, Claus, Calin-Jageman, Robert J., Davis, William E., Karekla, Maria, Zorjan, Saša, Jaremka, Lisa M., Uttley, Jim, Hricova, Monika, Koehn, Monica A., Kiselnikova, Natalia, Bai, Hui, Krafnick, Anthony J., Balci, Busra Bahar, Ballantyne, Tonia, Lins, Samuel, Vally, Zahir, Esteban-Serna, Celia, Schmidt, Kathleen, Macapagal, Paulo Manuel L., Szwed, Paulina, Zdybek, Przemysław Marcin, Moreau, David, Collins, W. Matthew, Joy-Gaba, Jennifer A., Vilares, Iris, Tran, Ulrich S., Boudesseul, Jordane, Albayrak-Aydemir, Nihan, Dixson, Barnaby James Wyld, Perillo, Jennifer T., Ferreira, Ana, Westgate, Erin C., Aberson, Christopher L., Arinze, Azuka Ikechukwu, Jaeger, Bastian, Butt, Muhammad Mussaffa, Silva, Jaime R., Storage, Daniel Shafik, Janak, Allison P., Jiménez-Leal, William, Soto, Jose A., Sorokowska, Agnieszka, McCarthy, Randy, Tullett, Alexa M., Frias-Armenta, Martha, Ribeiro, Matheus Fernando Felix, Hartanto, Andree, Forbes, Paul A.G., Willis, Megan L., del Carmen Tejada R, María, Torres, Adriana Julieth Olaya, Stephen, Ian D., Vaidis, David C., de la Rosa-Gómez, Anabel, Yu, Karen, Sutherland, Clare A.M., Manavalan, Mathi, Behzadnia, Behzad, Urban, Jan, Baskin, Ernest, McFall, Joseph P., Ogbonnaya, Chisom Esther, Fu, Cynthia H.Y., Rahal, Rima Maria, Ndukaihe, Izuchukwu L.G., Hostler, Thomas J., Kappes, Heather Barry, Sorokowski, Piotr, Khosla, Meetu, Lazarevic, Ljiljana B., Eudave, Luis, Vilsmeier, Johannes K., Luis, Elkin O., Muda, Rafał, Agadullina, Elena, Cárcamo, Rodrigo A., Reeck, Crystal, Anjum, Gulnaz, Venegas, Mónica Camila Toro, Misiak, Michal, Ryan, Richard M., Nock, Nora L., Travaglino, Giovanni A., Mensink, Michael C., Feldman, Gilad, Wichman, Aaron L., Chou, Weilun, Ziano, Ignazio, Seehuus, Martin, Chopik, William J., Kung, Franki Y.H., Carpentier, Joelle, Vaughn, Leigh Ann, Du, Hongfei, Xiao, Qinyu, Lima, Tiago J.S., Noone, Chris, Onie, Sandersan, Verbruggen, Frederick, Radtke, Theda, Primbs, Maximilian A., Lewis, David M. G., Buchanan, Erin M [0000-0002-9689-4189], Lewis, Savannah C [0000-0002-9948-1195], Paris, Bastien [0000-0002-7197-8001], Forscher, Patrick S [0000-0002-7763-3565], Silan, Miguel Alejandro A [0000-0002-7480-3661], IJzerman, Hans [0000-0002-0990-2276], Suchow, Jordan W [0000-0001-9848-4872], Coles, Nicholas A [0000-0001-8583-5610], Levitan, Carmel A [0000-0001-5403-444X], Azevedo, Flávio [0000-0001-9000-8513], Legate, Nicole [0000-0001-8086-9643], Rees, Vaughan W [0000-0002-9939-6740], von Bastian, Claudia C [0000-0002-0667-2460], Ruiz-Fernandez, Susana [0000-0002-1709-1506], Reggev, Niv [0000-0002-5734-7457], Zickfeld, Janis H [0000-0001-7660-2719], Akkas, Handan [0000-0002-2082-0685], Ropovik, Ivan [0000-0001-5222-1233], Gjoneska, Biljana [0000-0003-1200-6672], Warmelink, Lara [0000-0003-1218-9448], Stieger, Stefan [0000-0002-7784-6624], Fedotov, Maksim [0000-0002-7100-1719], Antfolk, Jan [0000-0003-0334-4987], Marcu, Gabriela-Mariana [0000-0003-2508-3749], Schrötter, Jana [0000-0002-9830-6184], Geiger, Sandra J [0000-0002-3262-5609], Adetula, Adeyemi [0000-0001-9344-576X], Kačmár, Pavol [0000-0003-0076-1945], Galindo-Caballero, Oscar J [0000-0003-4603-6415], Jernsäther, Teodor [0000-0002-7030-3299], Rachev, Nikolay R [0000-0002-5654-2883], Koptjevskaja-Tamm, Maria [0000-0002-9592-5780], Pit, Ilse L [0000-0002-4066-8086], Li, Ranran [0000-0001-9145-4240], Baník, Gabriel [0000-0002-6601-3619], Studzinska, Anna [0000-0002-7694-4214], Berkessel, Jana B [0000-0001-5053-6901], Morales-Izquierdo, Sara [0000-0003-3240-9348], Chuan-Peng, Hu [0000-0002-7503-5131], Beitner, Julia [0000-0002-2539-7011], Kowal, Marta [0000-0001-9050-1471], Schmidt, Nadya-Daniela [0000-0002-7229-2132], Szala, Anna [0000-0002-9693-9834], Vranka, Marek A [0000-0003-3413-9062], Białek, Michał [0000-0002-5062-5733], Maturan, Princess Lovella G [0000-0001-6762-1475], Kassianos, Angelos P [0000-0001-6428-2623], Adoric, Vera Cubela [0000-0003-4752-4541], Aczel, Balazs [0000-0001-9364-4988], Yamada, Yuki [0000-0003-1431-568X], Volz, Leonhard [0000-0001-7954-3793], Sunami, Naoyuki [0000-0001-5482-8370], Suter, Lilian [0000-0001-5655-3729], Mokady, Aviv [0000-0003-4475-0332], Adamkovic, Matus [0000-0002-9648-9108], Cohen, Noga [0000-0002-7682-0289], Krupić, Dino [0000-0003-4383-7807], Nilsonne, Gustav [0000-0001-5273-0150], Solorzano, Claudio Singh [0000-0003-0402-4969], Bavolar, Jozef [0000-0003-0179-7261], Becker, Maja [0000-0003-1187-1699], Kozma, Luca [0000-0002-3297-629X], Domurat, Artur [0000-0001-5533-9106], Parzuchowski, Michal [0000-0002-8960-0277], Czamanski-Cohen, Johanna [0000-0003-3980-6848], Pronizius, Ekaterina [0000-0003-1446-196X], Musser, Erica D [0000-0003-0966-4068], Sirota, Miroslav [0000-0003-2117-9532], Ross, Robert M [0000-0001-8711-1675], Foroni, Francesco [0000-0002-4702-3678], Almeida, Inês AT [0000-0003-0230-3075], Grigoryev, Dmitry [0000-0003-4511-7942], Lewis, David MG [0000-0002-8267-5727], Holford, Dawn L [0000-0002-6392-3991], Janssen, Steve MJ [0000-0002-3100-128X], Tatachari, Srinivasan [0000-0003-1838-2361], Batres, Carlota [0000-0002-3833-7667], Olofsson, Jonas K [0000-0002-0856-0569], Belaus, Anabel [0000-0001-9657-8496], Pfuhl, Gerit [0000-0002-3271-6447], Voracek, Martin [0000-0001-6109-6155], DeBruine, Lisa M [0000-0002-7523-5539], Arvanitis, Alexios [0000-0002-3379-0286], Arinze, Nwadiogo Chisom [0000-0002-2531-6250], Lamm, Claus [0000-0002-5422-0653], Calin-Jageman, Robert J [0000-0002-9837-6529], Karekla, Maria [0000-0001-7021-7908], Hricova, Monika [0000-0001-9873-5475], Koehn, Monica A [0000-0002-4413-7709], Krafnick, Anthony J [0000-0002-1692-0413], Lins, Samuel [0000-0001-6824-4691], Albayrak-Aydemir, Nihan [0000-0003-3412-4311], Dixson, Barnaby James Wyld [0000-0003-0911-1244], Butt, Muhammad Mussaffa [0000-0001-5271-111X], Sorokowska, Agnieszka [0000-0003-3999-8851], Willis, Megan L [0000-0002-2310-0018], Stephen, Ian D [0000-0001-9714-8295], Ogbonnaya, Chisom Esther [0000-0001-6392-0865], Fu, Cynthia HY [0000-0003-4313-3500], Rahal, Rima-Maria [0000-0002-1404-0471], Lazarevic, Ljiljana B [0000-0003-1629-3699], Reeck, Crystal [0000-0002-1540-5321], Travaglino, Giovanni A [0000-0003-4091-0634], Chopik, William J [0000-0003-1748-8738], Xiao, Qinyu [0000-0002-9824-9247], Verbruggen, Frederick [0000-0002-7958-0719], Apollo - University of Cambridge Repository, MÜ, Eğitim Fakültesi, Eğitim Bilimleri Bölümü, Kocalar, Halil Emre, Repositório da Universidade de Lisboa, Organizational Psychology, Center Ph. D. Students, Department of Social Psychology, Medical and Clinical Psychology, Clinical Psychology, and Faculdade de Psicologia e de Ciências da Educação

Subjects
Statistics and Probability, 223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, BF Psychology, 230 Affective Neuroscience, Health Behavior, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73, Message framing, Diseases, Library and Information Sciences, Ciências Sociais::Psicologia [Domínio/Área Científica], geographical and cultural context characterization, HV Social pathology. Social and public welfare. Criminology, pandemiat, Education, a general questionnaire examining health prevention behaviors and COVID-19 experience, ddc:150, SDG 3 - Good Health and Well-being, RA0421 Public health. Hygiene. Preventive Medicine, Surveys and Questionnaires, Adaptation, Psychological, yleiskartoitukset, Humans, Pendiente, Health behaviors, Pandemics, framing, Behaviour Change and Well-being, Emotion regulation, Self-determination messaging, and self-determination across a diverse, COVID-19, kansainvälinen vertailu, Research data, Computer Science Applications, which can be merged with other time-sampled or geographic data, cognitive reappraisals, global sample obtained at the onset of the COVID-19 pandemic, terveyskäyttäytyminen, In response to the COVID-19 pandemic, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, Statistics, Probability and Uncertainty, People’s health, tutkimusaineisto, survey-tutkimus, Dataset, Information Systems, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing
Abstract

Funder: Amazon Web Services (AWS) Imagine Grant, Funder: Kingston University (Kingston University, London); doi: https://doi.org/10.13039/100010049, Funder: Association Nationale de la Recherche et de la Technologie (National Association for Research and Technology); doi: https://doi.org/10.13039/501100003032, Funder: Association Nationale de la Recherche Scientifique and Pacifica (CIFRE grant 2017/0245), Funder: PRIMUS/20/HUM/009, Funder: UID/PSI/03125/2019 from the Portuguese National Foundation for Science and Technology (FCT)., Funder: PSA research grant ($285.59) for the PSACR projects data collection, Funder: The work of Dmitrii Dubrov was supported within the framework of the Basic Research Program at HSE University, RF, Funder: Agentúra na podporu výskumu a vývoja (Slovak Research and Development Agency) - APVV-17-0596, Funder: Progres Q18, Charles University, Funder: JSPS KAKENHI Grant Numbers JP18K12015 and JP20H04581, Funder: National Science Centre, Poland (2019/35/B/HS6/00528), Funder: Slovak Research and Development Agency - APVV-17-0596, Funder: Huo Family Foundation, Funder: The Japan Society for the Promotion of Science KAKENHI [19K14370], Funder: The Institute of Psychology, Jagiellonian University, Funder: Program FUTURE LEADER of Lorraine Université d’Excellence within the program Investissements Avenir (ANR-15-IDEX-04-LUE) operated by the French National Research Agency, Funder: Rubicon grant (019.183SG.007) from the Netherlands Organization for Scientific Research (NWO), Funder: Australian Research Council (DP180102384), Funder: HSE University Basic Research Program, Funder: Horizon 2020 grant 964728 (JITSUVAX) from the European Commission and was supported by a United Kingdom Research and Innovation (UKRI) Research Fellowship grant ES/V011901/1, Funder: Social Science and Humanities Research Council of Canada, Funder: Dominican University Faculty Support Grant, Funder: FONDECYT 1221538, Funder: Vicerrectoria de Investigaciones, Uniandes, Funder: Statutory funds of the Institute of Psychology, University of Wroclaw, Funder: University of Desarrollo, Faculty of Psychology, Funder: IDN Being Human Lab (University of Wrocław), Funder: ANID - Fondecyt 1201513, In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.

Published
2023

18. Expression of chimeric receptor CD4ζ by natural killer cells derived from human pluripotent stem cells improves in vitro activity but does not enhance suppression of HIV infection in vivo.

Author

Ni, Zhenya, Knorr, David A, Bendzick, Laura, Allred, Jeremy, and Kaufman, Dan S

Subjects
Killer Cells, Natural, Cell Line, Animals, Humans, Mice, HIV-1, HIV Infections, Antigens, CD4, Recombinant Fusion Proteins, Stem Cell Transplantation, Gene Expression Regulation, Embryonic Stem Cells, Induced Pluripotent Stem Cells, HIV-1 infection inhibition, Human embryonic stem cells, In vitro, In vivo, Induced pluripotent stem cells, Natural killer cells, CD4 Antigens, Killer Cells, Natural, Antigens, CD4, Biological Sciences, Technology, Medical and Health Sciences, Immunology
Abstract

Cell-based immunotherapy has been gaining interest as an improved means to treat human immunodeficiency virus (HIV)/AIDS. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) could become a potential resource. Our previous studies have shown hESC and iPSC-derived natural killer (NK) cells can inhibit HIV-infected targets in vitro. Here, we advance those studies by expressing a HIV chimeric receptor combining the extracellular portion of CD4 to the CD3ζ intracellular signaling chain. We hypothesized that expression of this CD4ζ receptor would more efficiently direct hESC- and iPSC-derived NK cells to target HIV-infected cells. In vitro studies showed the CD4ζ expressing hESC- and iPSC-NK cells inhibited HIV replication in CD4+ T-cells more efficiently than their unmodified counterparts. We then evaluated CD4ζ expressing hESC (CD4ζ-hESC)- and iPSC-NK cells in vivo anti-HIV activity using a humanized mouse model. We demonstrated significant suppression of HIV replication in mice treated with both CD4ζ-modified and -unmodified hESC-/iPSC-NK cells compared with control mice. However, we did not observe significantly increased efficacy of CD4ζ expression in suppression of HIV infection. These studies indicate that hESC/iPSC-based immunotherapy can be used as a unique resource to target HIV/AIDS.

Published
2014

19. Estrogen Receptor Status by Immunohistochemistry Is Superior to the Ligand-Binding Assay for Predicting Response to Adjuvant Endocrine Therapy in Breast Cancer

Author

Jennet Harvey, D. Craig Allred, Gary M. Clark, and C. Kent Osborne

Subjects
Oncology, Adult, medicine.medical_specialty, Pathology, Cancer Research, medicine.drug_class, medicine.medical_treatment, Mammary gland, Statistics as Topic, Estrogen receptor, Breast Neoplasms, Ligands, Breast cancer, Predictive Value of Tests, Internal medicine, Biomarkers, Tumor, Medicine, Humans, Estrogen Receptor Status, Aged, biology, business.industry, Middle Aged, medicine.disease, Prognosis, Immunohistochemistry, medicine.anatomical_structure, Receptors, Estrogen, Estrogen, Chemotherapy, Adjuvant, biology.protein, Female, Reagent Kits, Diagnostic, Antibody, business, Adjuvant
Abstract

PURPOSE Immunohistochemistry (IHC) is a newer technique for assessing the estrogen receptor (ER) status of breast cancers, with the potential to overcome many of the shortcomings associated with the traditional ligand-binding assay (LBA). The purpose of this study was to evaluate the ability of ER status determination by IHC, compared with LBA, to predict clinical outcome—especially response to adjuvant endocrine therapy—in a large number of patients with long-term clinical follow-up. PATIENTS AND METHODS ER status was evaluated in 1,982 primary breast cancers by IHC on formalin-fixed paraffin-embedded tissue sections, using antibody 6F11 and standard methodology. Slides were scored on a scale representing the estimated proportion and intensity of positive-staining tumor cells (range, 0 to 8). Results were compared with ER values obtained by the LBA in the same tumors and to clinical outcome. RESULTS An IHC score of greater than 2 (corresponding to as few as 1% to 10% weakly positive cells) was used to define ER positivity on the basis of a univariate cut-point analysis of all possible scores and disease-free survival (DFS) in patients receiving any adjuvant endocrine therapy. Using this definition, 71% of all tumors were determined to be ER-positive by IHC, and the level of agreement with the LBA was 86%. In multivariate analyses of patients receiving adjuvant endocrine therapy alone, ER status determined by IHC was better than that determined by the LBA at predicting improved DFS (hazard ratios/ P = 0.474/.0008 and 0.707/.3214, respectively) and equivalent at predicting overall survival (0.379/.0001 and 0.381/.0003, respectively). CONCLUSION IHC is superior to the LBA for assessing ER status in primary breast cancer because it is easier, safer, and less expensive, and has an equivalent or better ability to predict response to adjuvant endocrine therapy.

Published
2023

20. Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing

Author

Fang Chen, Xingyan Wang, Seon-Kyeong Jang, Bryan C. Quach, J. Dylan Weissenkampen, Chachrit Khunsriraksakul, Lina Yang, Renan Sauteraud, Christine M. Albert, Nicholette D. D. Allred, Donna K. Arnett, Allison E. Ashley-Koch, Kathleen C. Barnes, R. Graham Barr, Diane M. Becker, Lawrence F. Bielak, Joshua C. Bis, John Blangero, Meher Preethi Boorgula, Daniel I. Chasman, Sameer Chavan, Yii-Der I. Chen, Lee-Ming Chuang, Adolfo Correa, Joanne E. Curran, Sean P. David, Lisa de las Fuentes, Ranjan Deka, Ravindranath Duggirala, Jessica D. Faul, Melanie E. Garrett, Sina A. Gharib, Xiuqing Guo, Michael E. Hall, Nicola L. Hawley, Jiang He, Brian D. Hobbs, John E. Hokanson, Chao A. Hsiung, Shih-Jen Hwang, Thomas M. Hyde, Marguerite R. Irvin, Andrew E. Jaffe, Eric O. Johnson, Robert Kaplan, Sharon L. R. Kardia, Joel D. Kaufman, Tanika N. Kelly, Joel E. Kleinman, Charles Kooperberg, I-Te Lee, Daniel Levy, Sharon M. Lutz, Ani W. Manichaikul, Lisa W. Martin, Olivia Marx, Stephen T. McGarvey, Ryan L. Minster, Matthew Moll, Karine A. Moussa, Take Naseri, Kari E. North, Elizabeth C. Oelsner, Juan M. Peralta, Patricia A. Peyser, Bruce M. Psaty, Nicholas Rafaels, Laura M. Raffield, Muagututi’a Sefuiva Reupena, Stephen S. Rich, Jerome I. Rotter, David A. Schwartz, Aladdin H. Shadyab, Wayne H-H. Sheu, Mario Sims, Jennifer A. Smith, Xiao Sun, Kent D. Taylor, Marilyn J. Telen, Harold Watson, Daniel E. Weeks, David R. Weir, Lisa R. Yanek, Kendra A. Young, Kristin L. Young, Wei Zhao, Dana B. Hancock, Bibo Jiang, Scott Vrieze, and Dajiang J. Liu

Subjects
Tobacco Smoke and Health, Human Genome, Drug Repositioning, Single Nucleotide, Biological Sciences, Medical and Health Sciences, Brain Disorders, Tobacco Use, Substance Misuse, Good Health and Well Being, Tobacco, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, Transcriptome, Drug Abuse (NIDA only), Biology, Genome-Wide Association Study, Developmental Biology
Abstract

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction.

Published
2023

21. Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations

Author

Flaherty, Keith T, Infante, Jeffery R, Daud, Adil, Gonzalez, Rene, Kefford, Richard F, Sosman, Jeffrey, Hamid, Omid, Schuchter, Lynn, Cebon, Jonathan, Ibrahim, Nageatte, Kudchadkar, Ragini, Burris, Howard A, Falchook, Gerald, Algazi, Alain, Lewis, Karl, Long, Georgina V, Puzanov, Igor, Lebowitz, Peter, Singh, Ajay, Little, Shonda, Sun, Peng, Allred, Alicia, Ouellet, Daniele, Kim, Kevin B, Patel, Kiran, and Weber, Jeffrey

Subjects
Clinical Research, Cancer, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 6.2 Cellular and gene therapies, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Disease-Free Survival, Drug Therapy, Combination, Female, Fever, Humans, Imidazoles, MAP Kinase Signaling System, Male, Melanoma, Middle Aged, Mitogen-Activated Protein Kinase Kinases, Mutation, Oximes, Proto-Oncogene Proteins B-raf, Pyridones, Pyrimidinones, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundResistance to therapy with BRAF kinase inhibitors is associated with reactivation of the mitogen-activated protein kinase (MAPK) pathway. To address this problem, we conducted a phase 1 and 2 trial of combined treatment with dabrafenib, a selective BRAF inhibitor, and trametinib, a selective MAPK kinase (MEK) inhibitor.MethodsIn this open-label study involving 247 patients with metastatic melanoma and BRAF V600 mutations, we evaluated the pharmacokinetic activity and safety of oral dabrafenib (75 or 150 mg twice daily) and trametinib (1, 1.5, or 2 mg daily) in 85 patients and then randomly assigned 162 patients to receive combination therapy with dabrafenib (150 mg) plus trametinib (1 or 2 mg) or dabrafenib monotherapy. The primary end points were the incidence of cutaneous squamous-cell carcinoma, survival free of melanoma progression, and response. Secondary end points were overall survival and pharmacokinetic activity.ResultsDose-limiting toxic effects were infrequently observed in patients receiving combination therapy with 150 mg of dabrafenib and 2 mg of trametinib (combination 150/2). Cutaneous squamous-cell carcinoma was seen in 7% of patients receiving combination 150/2 and in 19% receiving monotherapy (P=0.09), whereas pyrexia was more common in the combination 150/2 group than in the monotherapy group (71% vs. 26%). Median progression-free survival in the combination 150/2 group was 9.4 months, as compared with 5.8 months in the monotherapy group (hazard ratio for progression or death, 0.39; 95% confidence interval, 0.25 to 0.62; P

Published
2012

22. Whole-genome analysis informs breast cancer response to aromatase inhibition

Author

Ellis, Matthew J, Ding, Li, Shen, Dong, Luo, Jingqin, Suman, Vera J, Wallis, John W, Van Tine, Brian A, Hoog, Jeremy, Goiffon, Reece J, Goldstein, Theodore C, Ng, Sam, Lin, Li, Crowder, Robert, Snider, Jacqueline, Ballman, Karla, Weber, Jason, Chen, Ken, Koboldt, Daniel C, Kandoth, Cyriac, Schierding, William S, McMichael, Joshua F, Miller, Christopher A, Lu, Charles, Harris, Christopher C, McLellan, Michael D, Wendl, Michael C, DeSchryver, Katherine, Allred, D Craig, Esserman, Laura, Unzeitig, Gary, Margenthaler, Julie, Babiera, GV, Marcom, P Kelly, Guenther, JM, Leitch, Marilyn, Hunt, Kelly, Olson, John, Tao, Yu, Maher, Christopher A, Fulton, Lucinda L, Fulton, Robert S, Harrison, Michelle, Oberkfell, Ben, Du, Feiyu, Demeter, Ryan, Vickery, Tammi L, Elhammali, Adnan, Piwnica-Worms, Helen, McDonald, Sandra, Watson, Mark, Dooling, David J, Ota, David, Chang, Li-Wei, Bose, Ron, Ley, Timothy J, Piwnica-Worms, David, Stuart, Joshua M, Wilson, Richard K, and Mardis, Elaine R

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Breast Cancer, Human Genome, Biotechnology, Anastrozole, Androstadienes, Antineoplastic Agents, Aromatase, Aromatase Inhibitors, Breast Neoplasms, DNA Repair, Exome, Exons, Female, Genetic Variation, Genome, Human, Humans, Letrozole, MAP Kinase Kinase 4, MAP Kinase Kinase Kinase 1, Mutation, Nitriles, Receptors, Estrogen, Treatment Outcome, Triazoles, General Science & Technology
Abstract

To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.

Published
2012

23. Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome.

Author

Engler, David A, Gupta, Sumeet, Growdon, Whitfield B, Drapkin, Ronny I, Nitta, Mai, Sergent, Petra A, Allred, Serena F, Gross, Jenny, Deavers, Michael T, Kuo, Wen-Lin, Karlan, Beth Y, Rueda, Bo R, Orsulic, Sandra, Gershenson, David M, Birrer, Michael J, Gray, Joe W, and Mohapatra, Gayatry

Subjects
Humans, Cystadenocarcinoma, Serous, Ovarian Neoplasms, Genetic Markers, Neoplasm Staging, Prognosis, Oligonucleotide Array Sequence Analysis, Survival Rate, Prospective Studies, Chromosome Mapping, Gene Expression Profiling, Adult, Aged, Aged, 80 and over, Middle Aged, Female, DNA Copy Number Variations, Neoplasm Grading, Cystadenocarcinoma, Serous, and over, General Science & Technology
Abstract

Ovarian cancer is the fifth leading cause of cancer death in women. Ovarian cancers display a high degree of complex genetic alterations involving many oncogenes and tumor suppressor genes. Analysis of the association between genetic alterations and clinical endpoints such as survival will lead to improved patient management via genetic stratification of patients into clinically relevant subgroups. In this study, we aim to define subgroups of high-grade serous ovarian carcinomas that differ with respect to prognosis and overall survival. Genome-wide DNA copy number alterations (CNAs) were measured in 72 clinically annotated, high-grade serous tumors using high-resolution oligonucleotide arrays. Two clinically annotated, independent cohorts were used for validation. Unsupervised hierarchical clustering of copy number data derived from the 72 patient cohort resulted in two clusters with significant difference in progression free survival (PFS) and a marginal difference in overall survival (OS). GISTIC analysis of the two clusters identified altered regions unique to each cluster. Supervised clustering of two independent large cohorts of high-grade serous tumors using the classification scheme derived from the two initial clusters validated our results and identified 8 genomic regions that are distinctly different among the subgroups. These 8 regions map to 8p21.3, 8p23.2, 12p12.1, 17p11.2, 17p12, 19q12, 20q11.21 and 20q13.12; and harbor potential oncogenes and tumor suppressor genes that are likely to be involved in the pathogenesis of ovarian carcinoma. We have identified a set of genetic alterations that could be used for stratification of high-grade serous tumors into clinically relevant treatment subgroups.

Published
2012

24. Breast Cancer Incidence in the Randomized PEARL Trial of Lasofoxifene in Postmenopausal Osteoporotic Women

Author

LaCroix, Andrea Z, Powles, Trevor, Osborne, C Kent, Wolter, Kevin, Thompson, John R, Thompson, David D, Allred, D Craig, Armstrong, Róisín, Cummings, Steve R, Eastell, Richard, Ensrud, Kristine E, Goss, Paul, Lee, Andrew, Neven, Patrick, Reid, David M, Curto, Madelyn, and Vukicevic, Slobodan

Subjects
Clinical Trials and Supportive Activities, Clinical Research, Estrogen, Cancer, Breast Cancer, Osteoporosis, Aging, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Aged, Aged, 80 and over, Anticarcinogenic Agents, Biomarkers, Tumor, Bone Density, Bone Density Conservation Agents, Breast Neoplasms, Carcinoma, Ductal, Breast, Case-Control Studies, Double-Blind Method, Estradiol, Female, Fractures, Bone, Humans, Incidence, Mammography, Middle Aged, Odds Ratio, Osteoporosis, Postmenopausal, Primary Prevention, Pyrrolidines, Receptors, Estrogen, Risk Assessment, Selective Estrogen Receptor Modulators, Sex Hormone-Binding Globulin, Tetrahydronaphthalenes, Treatment Outcome, United States, PEARL Investigators, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundCurrently available selective estrogen receptor modulators reduce the risk of breast cancer, but they are not widely used. In the Postmenopausal Evaluation and Risk-Reduction with Lasofoxifene (PEARL) trial, lasofoxifene was shown to reduce the risk of estrogen receptor-positive (ER+) breast cancer, nonvertebral and vertebral fractures, coronary artery disease, and stroke, but the effects on total breast cancer (invasive and ductal carcinoma in situ, ER+ and estrogen receptor-negative [ER-]) and ER+ invasive breast cancer are unknown.MethodsPostmenopausal women (n = 8556) aged 59-80 years with low bone density and normal mammograms were randomly assigned to two doses of lasofoxifene (0.25 and 0.5 mg) or placebo. The primary endpoints of the PEARL trial were incidence of ER+ breast cancer and nonvertebral fractures at 5 years. A nested case-control study of 49 incident breast cancer case patients and 156 unaffected control subjects from the PEARL trial was performed to evaluate treatment effects on risk of total and ER+ invasive breast cancer by baseline serum estradiol and sex hormone-binding globulin levels using logistic regression models. Cox proportional hazards models were used to evaluate risk of total breast cancer and ER+ invasive breast cancer using intention-to-treat analysis. All statistical tests were two-sided.ResultsBreast cancer was confirmed in 49 women. Compared with placebo, 0.5 mg of lasofoxifene statistically significantly reduced the risk of total breast cancer by 79% (hazard ratio = 0.21; 95% confidence interval [CI] = 0.08 to 0.55) and ER+ invasive breast cancer by 83% (hazard ratio = 0.17; 95% CI = 0.05 to 0.57). The effects of 0.5 mg of lasofoxifene on total breast cancer were similar regardless of Gail score, whereas the effects were markedly stronger for women with baseline estradiol levels greater than the median (odds ratio = 0.11; 95% CI = 0.02 to 0.51) vs those with levels less than the median (odds ratio = 0.78; 95% CI = 0.16 to 3.79; P(interaction) = .04).ConclusionA 0.5-mg dose of lasofoxifene appears to reduce the risks of both total and ER+ invasive breast cancer in postmenopausal women with osteoporosis.

Published
2010

25. Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial

Author

Robert H. Baloh, J. Patrick Johnson, Pablo Avalos, Peggy Allred, Soshana Svendsen, Genevieve Gowing, Kristina Roxas, Amanda Wu, Becky Donahue, Sheryl Osborne, George Lawless, Brandon Shelley, Koral Wheeler, Carolyn Prina, Dana Fine, Tami Kendra-Romito, Haniah Stokes, Vicki Manoukian, Abirami Muthukumaran, Leslie Garcia, Maria G. Bañuelos, Marlesa Godoy, Catherine Bresee, Hong Yu, Doniel Drazin, Lindsey Ross, Robert Naruse, Harish Babu, Eric A. Macklin, Ashley Vo, Ashraf Elsayegh, Warren Tourtellotte, Marcel Maya, Matthew Burford, Frank Diaz, Chirag G. Patil, Richard A. Lewis, and Clive N. Svendsen

Subjects
Disease Models, Animal, Neural Stem Cells, Spinal Cord, Superoxide Dismutase, Amyotrophic Lateral Sclerosis, Animals, Humans, Glial Cell Line-Derived Neurotrophic Factor, General Medicine, General Biochemistry, Genetics and Molecular Biology
Abstract

Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3–5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation.

Published
2022

26. The origins of estrogen receptor alpha-positive and estrogen receptor alpha-negative human breast cancer

Author

Allred, D Craig, Brown, Powel, and Medina, Daniel

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Breast Cancer, Estrogen, Antineoplastic Agents, Hormonal, Breast Neoplasms, Cell Growth Processes, Estrogen Receptor alpha, Humans, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Current hormonal therapies have benefited millions of patients with breast cancer. Their success, however, is often temporary and limited to a subset of patients whose tumors express estrogen receptor alpha (ER). The therapies are entirely ineffective in ER-negative disease. Recent studies suggest that there are many biological pathways and alterations involved in determining whether ER is expressed and how it is regulated during breast cancer evolution. Improving hormonal therapies, in addition to perfecting current strategies, will also target these newly discovered pathways and alterations, and others yet to be found. The present commentary will briefly highlight a few important observations and unanswered questions regarding ER status and growth regulation during breast cancer evolution, which hopefully will help to stimulate new thinking and progress in this important area of medial research.

Published
2004

27. Oncologic Outcomes of Multi-Institutional Minimally Invasive Inguinal Lymph Node Dissection for Melanoma Compared with Open Inguinal Dissection in the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II)

Author

James W. Jakub, Michael Lowe, J. Harrison Howard, Jeffrey M. Farma, Amod Sarnaik, Todd Tuttle, Heather B. Neuman, Charlotte E. Ariyan, Abhineet Uppal, Steve Trocha, Georgia M. Beasley, Nabil Wasif, Karl Y. Bilimoria, Alan A. Thomay, Jacob B. Allred, Lucia Chen, Alicia M. Terando, Jeffrey D. Wayne, John F. Thompson, Alistair J. Cochran, Myung-Shin Sim, David E. Elashoff, Keith A. Delman, and Mark B. Faries

Subjects
Skin Neoplasms, Oncology, Sentinel Lymph Node Biopsy, Humans, Lymph Node Excision, Surgery, Melanoma, Retrospective Studies
Abstract

Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes.This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS).For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND.This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.

Published
2022

28. A global experiment on motivating social distancing during the COVID-19 pandemic

Author

Legate, N, Ngyuen, T-V, Weinstein, N, Moller, A, Legault, L, Vally, Z, Tajchman, Z, Zsido, AN, Zrimsek, M, Chen, Z, Ziano, I, Gialitaki, Z, Ceary, CD, Jang, Y, Lin, Y, Kunisato, Y, Yamada, Y, Xiao, Q, Jiang, X, Du, X, Yao, E, Ryan, WS, Wilson, JP, Cyrus-Lai, W, Jimenez-Leal, W, Law, W, Unanue, W, Collins, WM, Richard, KL, Vranka, M, Ankushev, V, Schei, V, DePaola, C, Lerche, V, Kovic, V, Križanić, V, Kadreva, VH, Adoric, VC, Tran, US, Yeung, SK, Hassan, W, Houston, R, Machin, MA, Lima, TJS, Ostermann, T, Frizzo, T, Sverdrup, TE, House, T, Gill, T, Fedotov, M, Paltrow, T, Jernsäther, T, Rahman, T, Machin, T, Koptjevskaja-Tamm, M, Hostler, TJ, Ishii, T, Szaszi, B, Adamus, S, Suter, L, von Bormann, SM, Habib, S, Studzinska, A, Stojanovska, D, Janssen, SMJ, Stieger, S, Schulenberg, SE, Tatachari, S, Azouaghe, S, Sorokowski, P, Sorokowska, A, Song, X, Morbée, S, Lewis, S, Sinkolova, S, Grigoryev, D, Drexler, SM, Daches, S, Levine, SL, Geniole, SN, Akter, S, Vračar, S, Massoni, S, Costa, S, Zorjan, S, Sarioguz, E, Izquierdo, SM, Tshonda, SS, Alves, SG, Pöntinen, S, Solas, SÁ, Ordoñez-Riaño, S, Očovaj, SB, Onie, S, Lins, S, Biberauer, T, Çoksan, S, Khumkom, S, Sacakli, A, Ruiz-Fernández, S, Geiger, SJ, FatahModares, S, Walczak, RB, Betlehem, R, Vilar, R, Cárcamo, RA, Ross, RM, McCarthy, R, Ballantyne, T, Westgate, EC, Ryan, RM, Gargurevich, R, Afhami, R, Ren, D, Monteiro, RP, Reips, U-D, Reggev, N, Calin-Jageman, RJ, Pourafshari, R, Oliveira, R, Nedelcheva-Datsova, M, Rahal, R-M, Ribeiro, RR, Radtke, T, Searston, R, Jai-ai, R, Habte, R, Zdybek, P, Chen, S-C, Wajanatinapart, P, Maturan, PLG, Perillo, JT, Isager, PM, Kačmár, P, Macapagal, PM, Maniaci, MR, Szwed, P, Hanel, PHP, Forbes, PAG, Arriaga, P, Paris, B, Parashar, N, Papachristopoulos, K, Correa, PS, Kácha, O, Bernardo, M, Campos, O, Bravo, ON, Galindo-Caballero, OJ, Ogbonnaya, CE, Bialobrzeska, O, Kiselnikova, N, Simonovic, N, Cohen, N, Nock, NL, Hernandez, A, Thogersen-Ntoumani, C, Ntoumanis, N, Johannes, N, Albayrak-Aydemir, N, Say, N, Neubauer, AB, Martin, NI, Levy, N, Torunsky, N, Antwerpen, NV, Doren, NV, Sunami, N, Rachev, NR, Majeed, NM, Schmidt, N-D, Nadif, K, Corral-Frías, NS, Ouherrou, N, Abbas, N, Pantazi, M, Lucas, MY, Vasilev, MR, Victoria Ortiz, M, Butt, MM, Kurfalı, M, Kabir, M, Muda, R, Rivera, MDCMCT, Sirota, M, Seehuus, M, Parzuchowski, M, Toro, M, Hricova, M, Maldonado, MA, Rentzelas, P, Vansteenkiste, M, Metz, MA, Marszalek, M, Karekla, M, Mioni, G, Bosma, MJ, Westerlund, M, Vdovic, M, Bialek, M, Silan, MA, Anne, M, Misiak, M, Gugliandolo, MC, Grinberg, M, Capizzi, M, Espinoza Barría, MF, Kurfali, MA, Mensink, MC, Harutyunyan, M, Khosla, M, Dunn, MR, Korbmacher, M, Adamkovič, M, Ribeiro, MFF, Terskova, M, Hruška, M, Martončik, M, Jansen, M, Voracek, M, Čadek, M, Frias-Armenta, M, Kowal, M, Topor, M, Roczniewska, M, Oosterlinck, M, Kohlová, MB, Paruzel-Czachura, M, Sabristov, M, Romanova, M, Papadatou-Pastou, M, Lund, ML, Antoniadi, M, Magrin, ME, Jones, MV, Li, M, Ortiz, MS, Manavalan, M, Muminov, A, Kossowska, M, Friedemann, M, Wielgus, M, van Hooff, MLM, Varella, MAC, Standage, M, Nicolotti, M, Colloff, MF, Bradford, M, Vaughn, LA, Eudave, L, Vieira, L, Lu, JG, Pineda, LMS, Matos, L, Pérez, LC, Lazarevic, LB, Jaremka, LM, Smit, ES, Kushnir, E, Ferguson, LJ, Anton-Boicuk, L, Lins de Holanda Coelho, G, Ahlgren, L, Liga, F, Levitan, CA, Micheli, L, Gunton, L-A, Volz, L, Stojanovska, M, Boucher, L, Samojlenko, L, Delgado, LGJ, Kaliska, L, Beatrix, L, Warmelink, L, Rojas-Berscia, LM, Yu, K, Wylie, K, Wachowicz, J, Desai, K, Barzykowski, K, Kozma, L, Evans, K, Kirgizova, K, Emmanuel Agesin, BB, Koehn, MA, Wolfe, K, Korobova, T, Morris, K, Klevjer, K, van Schie, K, Vezirian, K, Damnjanović, K, Thommesen, KK, Schmidt, K, Filip, K, Staniaszek, K, Grzech, K, Hoyer, K, Moon, K, Khaobunmasiri, S, Rana, K, Janjić, K, Suchow, JW, Kielińska, J, Cruz Vásquez, JE, Chanal, J, Beitner, J, Vargas-Nieto, JC, Roxas, JCT, Taber, J, Urriago-Rayo, J, Pavlacic, JM, Benka, J, Bavolar, J, Soto, JA, Olofsson, JK, Vilsmeier, JK, Messerschmidt, J, Czamanski-Cohen, J, Waterschoot, J, Moss, JD, Boudesseul, J, Lee, JM, Kamburidis, J, Joy-Gaba, JA, Zickfeld, J, Miranda, JF, Verharen, JPH, Hristova, E, Beshears, JE, Djordjevic, JM, Bosch, J, Valentova, JV, Antfolk, J, Berkessel, JB, Schrötter, J, Urban, J, Röer, JP, Norton, JO, Silva, JR, Pickering, JS, Vintr, J, Uttley, J, Kunst, JR, Ndukaihe, ILG, Iyer, A, Vilares, I, Ivanov, A, Ropovik, I, Sula, I, Sarieva, I, Metin-Orta, I, Prusova, I, Pinto, I, Bozdoc, AI, Almeida, IAT, Pit, IL, Dalgar, I, Zakharov, I, Arinze, AI, Ihaya, K, Stephen, ID, Gjoneska, B, Brohmer, H, Flowe, H, Godbersen, H, Kocalar, HE, Hedgebeth, MV, Chuan-Peng, H, Sharifian, M, Manley, H, Akkas, H, Hajdu, N, Azab, H, Kaminski, G, Nilsonne, G, Anjum, G, Travaglino, GA, Feldman, G, Pfuhl, G, Czarnek, G, Marcu, GM, Hofer, G, Banik, G, Adetula, GA, Bijlstra, G, Verbruggen, F, Kung, FYH, Martela, F, Foroni, F, Forest, J, Singer, G, Muchembled, F, Azevedo, F, Mosannenzadeh, F, Marinova, E, Štrukelj, E, Etebari, Z, Bradshaw, EL, Baskin, E, Garcia, EOL, Musser, E, van Steenkiste, IMM, Ahn, ER, Quested, E, Pronizius, E, Jackson, EA, Manunta, E, Agadullina, E, Šakan, D, Dursun, P, Dujols, O, Dubrov, D, Willis, M, Tümer, M, Beaudry, JL, Popović, D, Dunleavy, D, Djamai, I, Krupić, D, Herrera, D, Vega, D, Du, H, Mola, D, Chakarova, D, Davis, WE, Holford, DL, Lewis, DMG, Vaidis, DC, Ozery, DH, Ricaurte, DZ, Storage, D, Sousa, D, Alvarez, DS, Boller, D, Rosa, AD, Dimova, D, Marko, D, Moreau, D, Reeck, C, Correia, RC, Whitt, CM, Lamm, C, Solorzano, CS, von Bastian, CC, Sutherland, CAM, Overkott, C, Aberson, CL, Wang, C, Niemiec, CP, Karashiali, C, Noone, C, Chiu, F, Picciocchi, C, Brownlow, C, Karaarslan, C, Cellini, N, Esteban-Serna, C, Reyna, C, Ferreyra, C, Batres, C, Li, R, Grano, C, Carpentier, J, Tamnes, CK, Fu, CHY, Ishkhanyan, B, Bylinina, L, Jaeger, B, Bundt, C, Allred, TB, Vermote, BJ, Bokkour, A, Bogatyreva, N, Shi, J, Chopik, WJ, Antazo, B, Behzadnia, B, Becker, M, Bayyat, MM, Cocco, B, Chou, W-L, Barkoukis, V, Hubena, B, Žuro, B, Aczel, B, Baklanova, E, Bai, H, Balci, BB, Babinčák, P, Soenens, B, Dixson, BJW, Mokady, A, Kappes, HB, Atari, M, Szala, A, Szabelska, A, Aruta, JJB, Domurat, A, Arinze, NC, Modena, A, Adiguzel, A, Monajem, A, ARABI, KAITEL, Özdoğru, AA, Rothbaum, AO, Torres, AO, Theodoropoulou, A, Skowronek, A, Jurković, AP, Singh, A, Kassianos, AP, Findor, A, Hartanto, A, Landry, AT, Ferreira, A, Santos, AC, De la Rosa-Gomez, A, Gourdon-Kanhukamwe, A, Luxon, AM, Todsen, AL, Karababa, A, Janak, A, Pilato, A, Bran, A, Tullett, AM, Kuzminska, AO, Krafnick, AJ, Urooj, A, Khaoudi, A, Ahmed, A, Groyecka-Bernard, A, Askelund, AD, Adetula, A, Belaus, A, Charyate, AC, Wichman, AL, Stoyanova, A, Greenburgh, A, Thomas, AG, Arvanitis, A, Forscher, PS, Mallik, PR, Coles, NA, Miller, JK, Moshontz, H, Urry, HL, IJzerman, H, Basnight-Brown, DM, Ebersole, CR, Chartier, CR, Buchanan, EM, Primbs, MA, Department of Psychology, Education and Child Studies, Clinical Psychology, Legate, N, Nguyen, T, Weinstein, N, Moller, A, Legault, L, Vally, Z, Tajchman, Z, Zsido, A, Zrimsek, M, Chen, Z, Ziano, I, Gialitaki, Z, Ceary, C, Jang, Y, Lin, Y, Kunisato, Y, Yamada, Y, Xiao, Q, Jiang, X, Du, X, Yao, E, Ryan, W, Wilson, J, Cyrus-Lai, W, Jimenez-Leal, W, Law, W, Unanue, W, Collins, W, Richard, K, Vranka, M, Ankushev, V, Schei, V, Lerche, V, Kovic, V, Krizanic, V, Kadreva, V, Adoric, V, Tran, U, Yeung, S, Hassan, W, Houston, R, Machin, M, Lima, T, Ostermann, T, Frizzo, T, Sverdrup, T, House, T, Gill, T, Fedotov, M, Paltrow, T, Jernsather, T, Rahman, T, Machin, T, Koptjevskaja-Tamm, M, Hostler, T, Ishii, T, Szaszi, B, Adamus, S, Suter, L, von Bormann, S, Habib, S, Studzinska, A, Stojanovska, D, Janssen, S, Stieger, S, Schulenberg, S, Tatachari, S, Azouaghe, S, Sorokowski, P, Sorokowska, A, Song, X, Morbee, S, Lewis, S, Sinkolova, S, Grigoryev, D, Drexler, S, Daches, S, Levine, S, Geniole, S, Akter, S, Vracar, 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C., De La Rosa-Gomez, A., Gourdon-Kanhukamwe, A., Luxon, A. M., Todsen, A. L., Karababa, A., Janak, A., Pilato, A., Bran, A., Tullett, A. M., Kuzminska, A. O., Krafnick, A. J., Department of Industrial Engineering and Management, Aalto-yliopisto, Aalto University, Massey, D., Kurfali, Merve A., Collaboration, Psychological Science Accelerator Self-Determination Theory, FdR overig onderzoek, Persuasive Communication (ASCoR, FMG), and Organizational Psychology

Subjects
behavior change, Coronavirus disease 2019 (COVID-19), 230 Affective Neuroscience, INTENTIONS, L400, self-determination theory, Physical Distancing, Social Sciences, Intention, Ciências Sociais::Psicologia [Domínio/Área Científica], FATIGUE, motivation, PARENTAL PROHIBITION, SDG 3 - Good Health and Well-being, Pandemic, Humans, health communication, MESSAGES, Sociology, Pandemics, METAANALYSIS, COVID-19, Behaviour Change and Well-being, Multidisciplinary, business.industry, Social distance, Public relations, Motivation, INTERNALIZATION, business, BEHAVIOR
Abstract

Significance\ud \ud Communicating in ways that motivate engagement in social distancing remains a critical global public health priority during the COVID-19 pandemic. This study tested motivational qualities of messages about social distancing (those that promoted choice and agency vs. those that were forceful and shaming) in 25,718 people in 89 countries. The autonomy-supportive message decreased feelings of defying social distancing recommendations relative to the controlling message, and the controlling message increased controlled motivation, a less effective form of motivation, relative to no message. Message type did not impact intentions to socially distance, but people’s existing motivations were related to intentions. Findings were generalizable across a geographically diverse sample and may inform public health communication strategies in this and future global health emergencies.\ud \ud \ud \ud Abstract\ud \ud Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.

Published
2022

29. Estrogen Protects Cardiac Function and Energy Metabolism in Dilated Cardiomyopathy Induced by Loss of Cardiac IRS1 and IRS2

Author

Hui Yan, Wanbao Yang, Fenghua Zhou, Quan Pan, Kimberly Allred, Clinton Allred, Yuxiang Sun, David Threadgill, David Dostal, Carl Tong, and Shaodong Guo

Subjects
Cardiomyopathy, Dilated, Heart Failure, Male, Mice, Knockout, Estrogens, Article, Mice, Diabetes Mellitus, Type 2, Insulin Receptor Substrate Proteins, Animals, Humans, Female, Insulin Resistance, Energy Metabolism, Cardiology and Cardiovascular Medicine
Abstract

Background: Type 2 diabetes (T2D) is a high-risk factor for incident of cardiovascular diseases. Women at young ages show a reduced incidence of both T2D and cardiovascular diseases compared with men, but these disparities disappear in postmenopausal women versus age-matched men. Thus, ovaries and ovarian hormones, such as estrogen, are expected to protect from T2D and cardiovascular diseases. In this study, we aimed to investigate the role of ovaries and ovarian hormone estrogen in cardiac function and energy metabolism using the cardiac IRS (insulin receptor substrate) 1 and IRS2 double genes knockout mice that mimic cardiac insulin resistance. Methods: Control and heart-specific IRS1/2 double genes knockout mice were treated with placebo or 17β-estradiol (E 2 ) pellets, respectively, through subcutaneous implantation. Female mice were subjected to a bilateral ovariectomy surgery to remove endogenous E 2 . The cardiac function and energy metabolism were determined using echocardiography and indirect calorimeter, respectively. Results: All male heart-specific IRS1/2 double genes knockout mice died of heart failure at 6 to 8 weeks as we previously described (Qi et al), but all female heart-specific IRS1/2 double genes knockout mice survived >1 year. Removal of ovaries in heart-specific IRS1/2 double genes knockout female mice resulted in cardiac dysfunction, and ultimately animal death. However, E 2 supplementation prevented the dilated cardiomyopathy, improved cardiac function and energy metabolism, and enhanced lifespan in both male and ovariectomy female mice deficient for cardiac IRS1 and IRS2 genes, largely owing to the activation of Akt (protein kinase B)-Foxo1 (O1 class of forkhead/winged helix transcription factor) signaling cascades. Conclusions: These results show that estrogen protects mice from cardiac insulin resistance-induced diabetic cardiomyopathy. This may provide a fundamental mechanism for the gender difference for the incidence of both T2D and cardiovascular diseases. This study highlights that estrogen signaling could be a potential target for improving cardiac function and energy metabolism in humans with T2D.

Published
2022

30. The Type 2 Diabetes Knowledge Portal: an open access genetic resource dedicated to type 2 diabetes and related traits

Author

Maria C. Costanzo, Marcin von Grotthuss, Jeffrey Massung, Dongkeun Jang, Lizz Caulkins, Ryan Koesterer, Clint Gilbert, Ryan P. Welch, Parul Kudtarkar, Quy Hoang, Andrew P. Boughton, Preeti Singh, Ying Sun, Marc Duby, Annie Moriondo, Trang Nguyen, Patrick Smadbeck, Benjamin R. Alexander, MacKenzie Brandes, Mary Carmichael, Peter Dornbos, Todd Green, Kenneth C. Huellas-Bruskiewicz, Yue Ji, Alexandria Kluge, Aoife C. McMahon, Josep M. Mercader, Oliver Ruebenacker, Sebanti Sengupta, Dylan Spalding, Daniel Taliun, Philip Smith, Melissa K. Thomas, Beena Akolkar, M. Julia Brosnan, Andriy Cherkas, Audrey Y. Chu, Eric B. Fauman, Caroline S. Fox, Tania Nayak Kamphaus, Melissa R. Miller, Lynette Nguyen, Afshin Parsa, Dermot F. Reilly, Hartmut Ruetten, David Wholley, Norann A. Zaghloul, Gonçalo R. Abecasis, David Altshuler, Thomas M. Keane, Mark I. McCarthy, Kyle J. Gaulton, Jose C. Florez, Michael Boehnke, Noël P. Burtt, Jason Flannick, Gonçalo Abecasis, Nicholette D. Allred, Jennifer E. Below, Richard Bergman, Joline W.J. Beulens, John Blangero, Krister Bokvist, Erwin Bottinger, Donald Bowden, Christopher Brown, Kenneth Bruskiewicz, Inês Cebola, John Chambers, Yii-Der Ida Chen, Christopher Clark, Melina Claussnitzer, Nancy J. Cox, Marcel den Hoed, Duc Dong, Ravindranath Duggirala, Josée Dupuis, Petra J.M. Elders, Jesse M. Engreitz, Eric Fauman, Jorge Ferrer, Paul Flicek, Matthew Flickinger, Timothy M. Frayling, Kelly A. Frazer, Anna L. Gloyn, Craig L. Hanis, Robert Hanson, Andrew T. Hattersley, Hae Kyung Im, Sidra Iqbal, Suzanne B.R. Jacobs, Dong-Keun Jang, Tad Jordan, Tania Kamphaus, Fredrik Karpe, Seung K. Kim, Kasper Lage, Leslie A. Lange, Mitchell Lazar, Donna Lehman, Ching-Ti Liu, Ruth J.F. Loos, Ronald Ching-wan Ma, Patrick MacDonald, Matthew T. Maurano, Gil McVean, James B. Meigs, Braxton Mitchell, Karen L. Mohlke, Samuel Morabito, Claire Morgan, Shannon Mullican, Sharvari Narendra, Maggie C.Y. Ng, Colin N.A. Palmer, Stephen C.J. Parker, Antonio Parrado, Aaron C. Pawlyk, Ewan R. Pearson, Andrew Plump, Michael Province, Thomas Quertermous, Susan Redline, Bing Ren, Stephen S. Rich, J. Brent Richards, Jerome I. Rotter, Rany M. Salem, Maike Sander, Michael Sanders, Dharambir Sanghera, Laura J. Scott, David Siedzik, Xueling Sim, Robert Sladek, Kerrin Small, Peter Stein, Heather M. Stringham, Katalin Susztak, Leen M. ’t Hart, Kent Taylor, Jennifer A. Todd, Miriam S. Udler, Benjamin Voight, Andre Wan, Kaan Yuksel, Epidemiology and Data Science, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, APH - Health Behaviors & Chronic Diseases, and General practice

Subjects
Physiology, data sharing, T2DKP, effector genes, Medical Biochemistry and Metabolomics, Article, Access to Information, Endocrinology & Metabolism, CMDKP, Diabetes Mellitus, genomics, Genetics, Humans, GWAS, Prospective Studies, Molecular Biology, Metabolic and endocrine, diabetes, Human Genome, Cell Biology, AMP-T2D Consortium, Phenotype, portal, Good Health and Well Being, genetic support, genetic associations, Biochemistry and Cell Biology, Type 2
Abstract

Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories of these data seek to be disease-agnostic and therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is a public resource of genetic datasets and genomic annotations dedicated to type 2 diabetes (T2D) and related traits. Here, we seek to make the T2DKP more accessible to prospective users and more useful to existing users. First, we evaluate the T2DKP's comprehensiveness by comparing its datasets with those of other repositories. Second, we describe how researchers unfamiliar with human genetic data can begin using and correctly interpreting them via the T2DKP. Third, we describe how existing users can extend their current workflows to use the full suite of tools offered by the T2DKP. We finally discuss the lessons offered by the T2DKP toward the goal of democratizing access to complex disease genetic results.

Published
2023

31. Municipal Ethnic Composition and Disparities in COVID-19 Infections in New Jersey: A Blinder–Oaxaca Decomposition Analysis

Author

Yuqi Wang, Laurent Reyes, Emily A. Greenfield, and Sarah R. Allred

Subjects
New Jersey, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Ethnicity, COVID-19, racial/ethnic disparity, health disparity, infection rate, Latinx, Humans, Healthcare Disparities, Pandemics, United States
Abstract

COVID-19 has disproportionally impacted Latinx and Black communities in the US. Our study aimed to extend the understanding of ethnic disparities in COVID-19 case rates by using a unique dataset of municipal case rates across New Jersey (NJ) during the first 17 months of the pandemic. We examined the extent to which there were municipal-level ethnic disparities in COVID-19 infection rates during three distinct spikes in case rates over this period. Furthermore, we used the Blinder–Oaxaca decomposition analysis to identify municipal-level exposure and vulnerability factors that contributed to ethnic disparities and how the contributions of these factors changed across the three initial waves of infection. Two clear results emerged. First, in NJ, the COVID-19 infection risk disproportionally affected Latinx communities across all three waves during the first 17 months of the pandemic. Second, the exposure and vulnerability factors that most strongly contributed to higher rates of infection in Latinx and Black communities changed over time as the virus, alongside medical and societal responses to it, also changed. These findings suggest that understanding and addressing ethnicity-based COVID-19 disparities will require sustained attention to the systemic and structural factors that disproportionately place historically marginalized ethnic communities at greater risk of contracting COVID-19.

Published
2022
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32. A method for quantitative evaluations of scanning‐proton dose distributions

Author

Todd A. DeWees, Daniel G. Robertson, Wei Liu, Bryce C. Allred, Jiajian Shen, Jie Shan, and Joshua B. Stoker

Subjects
Image registration, computer.software_genre, Standard deviation, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Voxel, Histogram, Technical Note, Proton Therapy, Humans, Radiology, Nuclear Medicine and imaging, Instrumentation, Mathematics, Radiation, Pixel, Radiotherapy Planning, Computer-Assisted, Isocenter, gamma test, Radiotherapy Dosage, Radius, PSQA, Pencil (optics), 030220 oncology & carcinogenesis, Technical Notes, Protons, computer, Algorithm, Algorithms, proton
Abstract

Purpose Patient‐Specific Quality Assurance (PSQA) measurement analysis depends on generating metrics representative of calculation and measurement agreement. Considering the heightened capability of discrete spot scanning protons to modulate individual dose voxels, a dose plane comparison approach that maintained all of the capabilities of the well‐established γ test, but that also provided a more intuitive error parameterization, was desired. Methods Analysis was performed for 300 dose planes compared by searching all calculated points within a fixed radius around each measured pixel to determine the dose deviation. Dose plane agreement is reported as the dose difference minimum (DDM) within an empirically established search radius: ΔDmin(r). This per‐pixel metric is aggregated into a histogram binned by dose deviation. Search‐radius criteria were based on a weighted‐beamlet 3σ spatial deviation from imaging isocenter. Equipment setup error was mitigated during analysis using tracked image registration, ensuring beamlet deviations to be the dominant source of spatial error. The percentage of comparison points with

Published
2021

33. Overcoming racism in the twin spheres of conservation science and practice

Author

Michael Dunaway, Andrea Dávalos, Tanesha M. Allen, Sara L. Middleton, Darragh Hare, Kumar Paudel, Claudio Sillero-Zubiri, Duan Biggs, Merlyn Nomusa Nkomo, Thembela Kepe, Shorna B. Allred, Amy Dickman, Meera Anna Oommen, Moreangels M. Mbizah, Lauren F. Rudd, Kartik Shanker, Julius G. Bright Ross, Ritwick Ghosh, Nicole Thompson González, Rudd, Lauren F [0000-0002-5925-9514], Allred, Shorna [0000-0001-6237-0638], Bright Ross, Julius G [0000-0003-2454-1592], Hare, Darragh [0000-0003-4418-9637], Nkomo, Merlyn Nomusa [0000-0002-0609-0153], Shanker, Kartik [0000-0003-4856-0093], González, Nicole Thompson [0000-0002-3195-1277], Kepe, Thembela [0000-0002-1807-0387], Mbizah, Moreangels M [0000-0002-6868-052X], Middleton, Sara L [0000-0001-5307-8029], Dávalos, Andrea [0000-0002-3590-4152], and Apollo - University of Cambridge Repository

Subjects
anti-racism, colonialism, Inclusion (disability rights), Anti-racism, media_common.quotation_subject, Colonialism, Racism, General Biochemistry, Genetics and Molecular Biology, Indigenous, diversity, equity, Humans, Conservation science, Sociology, Systemic Racism, General Environmental Science, media_common, Equity (economics), General Immunology and Microbiology, BIPOC, Environmental ethics, General Medicine, inclusion, Biological science practices, General Agricultural and Biological Sciences, Diversity (politics)
Abstract

It is time to acknowledge and overcome conservation's deep-seated systemic racism, which has historically marginalized Black, Indigenous and people of colour (BIPOC) communities and continues to do so. We describe how the mutually reinforcing ‘twin spheres’ of conservation science and conservation practice perpetuate this systemic racism. We trace how institutional structures in conservation science (e.g. degree programmes, support and advancement opportunities, course syllabuses) can systematically produce conservation graduates with partial and problematic conceptions of conservation's history and contemporary purposes. Many of these graduates go on to work in conservation practice, reproducing conservation's colonial history by contributing to programmes based on outmoded conservation models that disproportionately harm rural BIPOC communities and further restrict access and inclusion for BIPOC conservationists. We provide practical, actionable proposals for breaking vicious cycles of racism in the system of conservation we have with virtuous cycles of inclusion, equality, equity and participation in the system of conservation we want.

Published
2021

34. A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic

Author

IJzerman, Hans, Ropovik, Ivan, Ebersole, Charles, Tidwell, Natasha, Markiewicz, Łukasz, de Lima, Tiago Jessé Souza, Wolf, Daniel, Novak, Sarah, Collins, W. Matthew, Menon, Madhavi, de Souza, Luana Elayne Cunha, Sawicki, Przemysław, Boucher, Leanne, Białek, Michał, Idzikowska, Katarzyna, Razza, Timothy, Kraus, Sue, Weissgerber, Sophia, Baník, Gabriel, Kołodziej, Sabina, Babincak, Peter, Schütz, Astrid, Sternglanz, R. Weylin, Gawryluk, Katarzyna, Sullivan, Gavin Brent, Day, Chris, Sparacio, Alessandro, Tops, Mattie, Quirin, Markus, Lewis, Neil, Przybylski, Andrew, Weinstein, Netta, DeBruine, Lisa, Ritchie, Stuart, Vazire, Simine, Forscher, Patrick, Morey, Richard, Ivory, James, Anvari, Farid, Jones, Benedict, Flake, Jessica, Liuzza, Marco Tullio, Antfolk, Jan, Arinze, Nwadiogo, Ndukaihe, Izuchukwu, Bloxsom, Nicholas, Lewis, Savannah, Foroni, Francesco, Willis, Megan, Cubillas, Carmelo, Vadillo, Miguel, Turiegano, Enrique, Gilead, Michael, Simchon, Almog, Saribay, S. Adil, Owsley, Nicholas, Jang, Chaning, Mburu, Georgina, Calvillo, Dustin, Wlodarczyk, Anna, Qi, Yue, Ariyabuddhiphongs, Kris, Jarukasemthawee, Somboon, Manley, Harry, Suavansri, Panita, Taephant, Nattasuda, Stolier, Ryan, Evans, Thomas, Bonick, Judson, Lindemans, Jan, Ashworth, Logan, Hahn, Amanda, Chevallier, Coralie, Kapucu, Aycan, Karaaslan, Aslan, Leongómez, Juan David, Sánchez, Oscar, Valderrama, Eugenio, Vásquez-Amézquita, Milena, Hajdu, Nandor, Aczel, Balazs, Szecsi, Peter, Andreychik, Michael, Musser, Erica, Batres, Carlota, Hu, Chuan-Peng, Liu, Qing-Lan, Legate, Nicole, Vaughn, Leigh Ann, Barzykowski, Krystian, Golik, Karolina, Schmid, Irina, Stieger, Stefan, Artner, Richard, Mues, Chiel, Vanpaemel, Wolf, Jiang, Zhongqing, Wu, Qi, Marcu, Gabriela, Stephen, Ian, Lu, Jackson, Philipp, Michael, Arnal, Jack, Hehman, Eric, Xie, Sally, Chopik, William, Seehuus, Martin, Azouaghe, Soufian, Belhaj, Abdelkarim, Elouafa, Jamal, Wilson, John, Kruse, Elliott, Papadatou-Pastou, Marietta, De La Rosa-Gómez, Anabel, Barba-Sánchez, Alan, González-Santoyo, Isaac, Hsu, Tsuyueh, Kung, Chun-Chia, Wang, Hsiao-Hsin, Freeman, Jonathan, Oh, Dong Won, Schei, Vidar, Sverdrup, Therese, Levitan, Carmel, Cook, Corey, Chandel, Priyanka, Kujur, Pratibha, Parganiha, Arti, Parveen, Noorshama, Pati, Atanu Kumar, Pradhan, Sraddha, Singh, Margaret, Pande, Babita, Bavolar, Jozef, Kačmár, Pavol, Zakharov, Ilya, Álvarez-Solas, Sara, Baskin, Ernest, Thirkettle, Martin, Schmidt, Kathleen, Christopherson, Cody, Leonis, Trinity, Suchow, Jordan, Olofsson, Jonas, Jernsäther, Teodor, Lee, Ai-Suan, Beaudry, Jennifer, Gogan, Taylor, Oldmeadow, Julian, Balas, Benjamin, Stevens, Laura, Colloff, Melissa, Flowe, Heather, Gülgöz, Sami, Brandt, Mark, Hoyer, Karlijn, Jaeger, Bastian, Ren, Dongning, Sleegers, Willem, Wissink, Joeri, Kaminski, Gwenaël, Floerke, Victoria, Urry, Heather, Chen, Sau-Chin, Pfuhl, Gerit, Vally, Zahir, Basnight-Brown, Dana, Jzerman, Hans, Sarda, Elisa, Neyroud, Lison, Badidi, Touhami, Van der Linden, Nicolas, Tan, Chrystalle, Kovic, Vanja, Sampaio, Waldir, Ferreira, Paulo, Santos, Diana, Burin, Debora, Gardiner, Gwendolyn, Protzko, John, Schild, Christoph, Ścigała, Karolina, Zettler, Ingo, O’Mara Kunz, Erin, Storage, Daniel, Wagemans, Fieke, Saunders, Blair, Sirota, Miroslav, Sloane, Guyan, Lima, Tiago, Uittenhove, Kim, Vergauwe, Evie, Jaworska, Katarzyna, Stern, Julia, Ask, Karl, van Zyl, Casper, Körner, Anita, Boudesseul, Jordane, Ruiz-Dodobara, Fernando, Ritchie, Kay, Michalak, Nicholas, Blake, Khandis, White, David, Gordon-Finlayson, Alasdair, Anne, Michele, Janssen, Steve, Lee, Kean Mun, Nielsen, Tonje, Tamnes, Christian, Zickfeld, Janis, Rosa, Anna Dalla, Vianello, Michelangelo, Kocsor, Ferenc, Kozma, Luca, Putz, Ádám, Tressoldi, Patrizio, Irrazabal, Natalia, Chatard, Armand, Lins, Samuel, Pinto, Isabel, Lutz, Johannes, Adamkovic, Matus, Coetzee, Vinet, Dixson, Barnaby, Ribeiro, Gianni, Peters, Kim, Steffens, Niklas, Tan, Kok Wei, Thorstenson, Christopher, Fernandez, Ana Maria, Hsu, Rafael, Valentova, Jaroslava, Varella, Marco, Corral-Frías, Nadia, Frías-Armenta, Martha, Hatami, Javad, Monajem, Arash, Sharifian, MohammadHasan, Frohlich, Brooke, Lin, Hause, Inzlicht, Michael, Alaei, Ravin, Rule, Nicholas, Lamm, Claus, Pronizius, Ekaterina, Voracek, Martin, Olsen, Jerome, Giolla, Erik Mac, Akgoz, Aysegul, Özdoğru, Asil, Crawford, Matthew, Bennett-Day, Brooke, Koehn, Monica, Okan, Ceylan, Gill, Tripat, Miller, Jeremy, Dunham, Yarrow, Yang, Xin, Alper, Sinan, Borras-Guevara, Martha Lucia, Cai, Sun Jun, Tiantian, Dong, Danvers, Alexander, Feinberg, David, Armstrong, Marie, Gilboa-Schechtman, Eva, McCarthy, Randy, Muñoz-Reyes, Jose Antonio, Polo, Pablo, Shiramazu, Victor, Yan, Wen-Jing, Carvalho, Lilian, Chartier, Christopher, Coles, Nicholas, Klein, Richard, Dujols, Olivier, van de Ven, Niels, Pich, Olivia, Schubert, Thomas, Berkessel, Jana, Pizarro, José, Bhushan, Braj, Mateo, Nino Jose, Barbosa, Sergio, Sharman, Leah, Kökönyei, Gyöngyi, Schrover, Elke, Kardum, Igor, Aruta, John Jamir Benzon, Lazarevic, Ljiljana, Escobar, María Josefina, Stadel, Marie, Arriaga, Patrícia, Dodaj, Arta, Shankland, Rebecca, Majeed, Nadyanna, Li, Yansong, Lekkou, Eleimonitria, Hartanto, Andree, del Carmen Espinoza, Maria, Caballero, Amparo, Kolen, Anouk, Karsten, Julie, Maeura, Nao, Eşkisu, Mustafa, Shani, Yaniv, Chittham, Phakkanun, Ferreira, Diogo, Konova, Irina, Sato, Wataru, Morvinski, Coby, Carrera, Pilar, Villar, Sergio, Ibanez, Agustin, Hareli, Shlomo, Garcia, Adolfo, Kremer, Inbal, Götz, Friedrich, Schwerdtfeger, Andreas, Estrada-Mejia, Catalina, Nakayama, Masataka, Ng, Wee Qin, Sesar, Kristina, Orjiakor, Charles, Dumont, Kitty, Allred, Tara Bulut, Gračanin, Asmir, Rentfrow, Peter, Schönefeld, Victoria, Peltola, Henna-Riikka, Tcherkassof, Anna, Haque, Shamsul, Śmieja, Magdalena, Su-May, Terri Tan, Vatakis, Argiro, Ong, Chew Wei, Choi, Eunsoo, Schorch, Sebastian, Páez, Darío, Malik, Sadia, Bobowik, Magdalena, Jose, Paul, Vuoskoski, Jonna, Basabe, Nekane, Doğan, Uğur, Ebert, Tobias, Uchida, Yukiko, Zheng, Michelle Xue, Mefoh, Philip, Šebeňa, René, Stanke, Franziska, Ballada, Christine Joy, Blaut, Agata, Wu, Yang, Daniels, Judith, Kocsel, Natália, Burak, Elif Gizem Demirag, Balt, Nina, Vanman, Eric, Stewart, Suzanne L.K., Verschuere, Bruno, Sikka, Pilleriin, Martins, Diogo, Nussinson, Ravit, Ito, Kenichi, Mentser, Sari, Çolak, Tuğba Seda, Martinez-Zelaya, Gonzalo, Vingerhoets, Ad, Wang, Ke, Goldenberg, Amit, Dorison, Charles, Uusberg, Andero, Lerner, Jennifer, Gross, James, Agesin, Bamikole Bamikole, Bernardo, Márcia, Campos, Olatz, Eudave, Luis, Grzech, Karolina, Ozery, Daphna Hausman, Jackson, Emily, Garcia, Elkin Oswaldo Luis, Drexler, Shira Meir, Jurković, Anita Penić, Rana, Kafeel, Wilson, John Paul, Antoniadi, Maria, Desai, Kermeka, Gialitaki, Zoi, Kushnir, Elizaveta, Nadif, Khaoula, Bravo, Olalla Niño, Nauman, Rafia, Oosterlinck, Marlies, Pantazi, Myrto, Pilecka, Natalia, Szabelska, Anna, van Steenkiste, I., Filip, Katarzyna, Bozdoc, Andreea Ioana, Marcu, Gabriela Mariana, Agadullina, Elena, Roczniewska, Marta, Reyna, Cecilia, Kassianos, Angelos, Westerlund, Minja, Ahlgren, Lina, Pöntinen, Sara, Adetula, Gabriel Agboola, Dursun, Pinar, Arinze, Azuka Ikechukwu, Arinze, Nwadiogo Chisom, Ogbonnaya, Chisom Esther, Dalgar, Ilker, Akkas, Handan, Macapagal, Paulo Manuel, Metin-Orta, Irem, Santos, Anabela Caetano, Mokady, Aviv, Reggev, Niv, Kurfali, Merve, Vasilev, Martin, Nock, Nora, Parzuchowski, Michal, Espinoza Barría, Mauricio, Vranka, Marek, Kohlová, Markéta Braun, Harutyunyan, Mikayel, Wang, Chunhui, Yao, Elvin, Becker, Maja, Manunta, Efisio, Marko, Dafne, Evans, Kortnee, Lewis, David, Findor, Andrej, Landry, Anais Thibault, Ortiz, Manuel, Grinberg, Maurice, Li, Ranran, Valentova, Jaroslava Varella, Mioni, Giovanna, Cellini, Nicola, Moon, Karis, Azab, Habiba, Levy, Neil, Karababa, Alper, Todsen, Anna Louise, van Schie, Kevin, Vintr, Jáchym, Kaliska, Lada, Križanić, Valerija, Samojlenko, Lara, Pourafshari, Razieh, Geiger, Sandra, Beitner, Julia, Warmelink, Lara, Ross, Robert, Hostler, Thomas, Szala, Anna, Grano, Caterina, Solorzano, Claudio Singh, Anjum, Gulnaz, Jimenez-Leal, William, Bradford, Maria, Pérez, Laura Calderón, Cruz Vásquez, Julio, Galindo-Caballero, Oscar, Vargas-Nieto, Juan Camilo, Kácha, Ondřej, Arvanitis, Alexios, Xiao, Qinyu, Cárcamo, Rodrigo, Zorjan, Saša, Tajchman, Zuzanna, Vilares, Iris, Pavlacic, Jeffrey, Kunst, Jonas, von Bastian, Claudia, Atari, Mohammad, Hricova, Monika, Schrötter, Jana, Rahal, Rima-Maria, Cohen, Noga, FatahModarres, Saiedeh, Zrimsek, Miha, Esteban-Serna, Celia, Calin-Jageman, Robert, Krafnick, Anthony, Štrukelj, Eva, Isager, Peder Mortvedt, Urban, Jan, Silva, Jaime, Martončik, Marcel, Očovaj, Sanja Batić, Šakan, Dušana, Kuzminska, Anna, Djordjevic, Jasna Milosevic, Almeida, Inês, Ferreira, Ana, Ricaurte, Danilo Zambrano, Monteiro, Renan, Etabari, Zahra, Dunleavy, Daniel, Chou, Weilun, Godbersen, Hendrik, Ruiz-Fernández, Susana, Reeck, Crystal, Kirgizova, Komila, Muminov, Abdumalik, Azevedo, Flavio, Alvarez, Daniela Serrato, Butt, Muhammad Mussaffa, Lee, Jeong Min, Chen, Zhang, Verbruggen, Frederick, Ziano, Ignazio, Tümer, Murat, Charyate, Abdelilah, Dubrov, Dmitrii, Tejada Rivera, María del Carmen M. C., Aberson, Christopher, Pálfi, Bence, Maldonado, Mónica Alarcón, Hubena, Barbora, Sacakli, Asli, Ceary, Chris, Richard, Karley, Singer, Gage, Perillo, Jennifer, Ballantyne, Tonia, Cyrus-Lai, Wilson, Fedotov, Maksim, Du, Hongfei, Wielgus, Magdalena, Pit, Ilse, Hruška, Matej, Sousa, Daniela, Szaszi, Barnabas, Adamus, Sylwia, Micheli, Leticia, Schmidt, Nadya-Daniela, Zsido, Andras, Paruzel-Czachura, Mariola, Bialek, Michal, Kowal, Marta, Sorokowska, Agnieszka, Misiak, Michal, Mola, Débora, Ortiz, María Victoria, Correa, Pablo Sebastián, Belaus, Anabel, Muchembled, Fany, Ribeiro, Rafael, Oliveira, Raquel, Szwed, Paulina, Kossowska, Małgorzata, Czarnek, Gabriela, Kielińska, Julita, Antazo, Benedict, Betlehem, Ruben, Nilsonne, Gustav, Simonovic, Nicolle, Taber, Jennifer, Gourdon-Kanhukamwe, Amélie, Domurat, Artur, Ihaya, Keiko, Yamada, Yuki, Urooj, Anum, Čadek, Martin, Bylinina, Lisa, Messerschmidt, Johanna, Kurfalı, Murathan, Adetula, Adeyemi, Baklanova, Ekaterina, Albayrak-Aydemir, Nihan, Kappes, Heather, Gjoneska, Biljana, House, Thea, Jones, Marc, Çoksan, Sami, Khaoudi, Ahmed, Bokkour, Ahmed, El Arabi, Kanza Ait, Djamai, Ikhlas, Iyer, Aishwarya, Parashar, Neha, Adiguzel, Arca, Kocalar, Halil Emre, Bundt, Carsten, Norton, James, Ankushev, Vladislav, Bogatyreva, Natalia, Grigoryev, Dmitry, Ivanov, Aleksandr, Prusova, Irina, Romanova, Marina, Sarieva, Irena, Terskova, Maria, Hristova, Evgeniya, Kadreva, Veselina Hristova, Janak, Allison, Askelund, Adrian Dahl, Pineda, Lina Maria Sanabria, Krupić, Dajana, Johannes, Niklas, Ouherrou, Nihal, Say, Nicolas, Sinkolova, Sladjana, Janjić, Kristina, Stojanovska, Marija, Stojanovska, Dragana, Khosla, Meetu, Thomas, Andrew, Kung, Franki, Bijlstra, Gijsbert, Mosannenzadeh, Farnaz, Balci, Busra Bahar, Reips, Ulf-Dietrich, Ishkhanyan, Byurakn, Czamanski-Cohen, Johanna, Dixson, Barnaby James Wyld, Moreau, David, Sutherland, Clare, Chuan-Peng, Hu, Noone, Chris, Topor, Marta, Kunisato, Yoshihiko, Yu, Karen, Daches, Shimrit, Vdovic, Milica, Anton-Boicuk, Lisa, Forbes, Paul, Kamburidis, Julia, Marinova, Evelina, Nedelcheva-Datsova, Mina, Rachev, Nikolay, Stoyanova, Alina, Koptjevskaja-Tamm, Maria, Bialobrzeska, Olga, Marszalek, Magdalena, Tatachari, Srinivasan, Afhami, Reza, Law, Wilbert, Žuro, Barbara, Van Doren, Natalia, Soto, Jose, Searston, Rachel, Miranda, Jacob, Damnjanović, Kaja, Yeung, Siu Kit, Krupić, Dino, Klevjer, Kristoffer, Lucas, Marc, Torres, Adriana Olaya, Toro, Mónica, Delgado, Lady Grey Javela, Vega, Diego, Solas, Sara Álvarez, Vilar, Roosevelt, Massoni, Sébastien, Frizzo, Thomas, Bran, Alexandre, Vaidis, David, Vieira, Luc, Paris, Bastien, Capizzi, Mariagrazia, Coelho, Gabriel Lins de Holanda, Greenburgh, Anna, Whitt, Cassie, Tullett, Alexa, Du, Xinkai, Volz, Leonhard, Bosma, Minke Jasmijn, Karaarslan, Cemre, Sarıoğuz, Eylül, Korbmacher, Max, Ribeiro, Matheus Fernando Felix, Verharen, Jeroen, Karekla, Maria, Karashiali, Christiana, Sunami, Naoyuki, Jaremka, Lisa, Habib, Sumaiya, Studzinska, Anna, Hanel, Paul, Holford, Dawn Liu, Wolfe, Kelly, Chiu, Faith, Theodoropoulou, Andriana, Ahn, El Rim, Lin, Yijun, Westgate, Erin, Brohmer, Hilmar, Hofer, Gabriela, Vezirian, Kevin, Feldman, Gilad, Travaglino, Giovanni, Ahmed, Afroja, Li, Manyu, Bosch, Jasmijn, Torunsky, Nathan, Bai, Hui, Manavalan, Mathi, Song, Xin, Walczak, Radoslaw, Zdybek, Przemysław, Friedemann, Maja, Alves, Sara, Correia, Rita, Rojas-Berscia, Luis Miguel, Uttley, Jim, Beshears, Julie, Thommesen, Katrine Krabbe, Behzadnia, Behzad, Geniole, Shawn, Silan, Miguel, Maturan, Princess Lovella G., Vilsmeier, Johannes, Tran, Ulrich, Izquierdo, Sara Morales, Mensink, Michael, Sorokowski, Piotr, Groyecka-Bernard, Agata, Radtke, Theda, Adoric, Vera Cubela, Carpentier, Joelle, Özdoğru, Asil Ali, Joy-Gaba, Jennifer, Hedgebeth, Mattie, Ishii, Tatsunori, Wichman, Aaron, Röer, Jan Philipp, Ostermann, Thomas, Davis, William, Suter, Lilian, Papachristopoulos, Konstantinos, Zabel, Chelsea, Mallik, Peter, Buchanan, Erin, Primbs, Maximilian, Moshontz, Hannah, Clinical Psychology, Medical Oncology, Laboratoire Inter-universitaire de Psychologie : Personnalité, Cognition, Changement Social (LIP-PC2S), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Akdemir KurfalI, Merve, Cognition, Langues, Langage, Ergonomie (CLLE-LTC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Toulouse - Jean Jaurès (UT2J)-Centre National de la Recherche Scientifique (CNRS), Organizational Psychology, Medical and Clinical Psychology, Department of Social Psychology, Repositório da Universidade de Lisboa, Faculdade de Psicologia e de Ciências da Educação, and PDF ist zur Bearb. im Hiwi-Ordner, Sperre bis 28.02.2022, rechtl. Bedingungen: postprint, 6 Monate Embargo (Sherpa), 26.01.2022 bo

Subjects
Male, STRESS, Emotions, Psychological intervention, Social Sciences, [SHS.PSY]Humanities and Social Sciences/Psychology, REAPPRAISAL INTERVENTIONS, Behavioral neuroscience, NEGATIVE AND POSITIVE EMOTIONS, Behavioral Neuroscience, 0302 clinical medicine, ddc:150, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], Pandemic, Psychology, ANXIETY, Covid-19, reappraisal, emotions, R PACKAGE, purl.org/becyt/ford/5.1 [https], ComputingMilieux_MISCELLANEOUS, Repurposing, media_common, purl.org/becyt/ford/5 [https], 05 social sciences, DIVERGENT ASSOCIATIONS, POSITIVE EMOTIONS, 3. Good health, [SCCO.PSYC]Cognitive science/Psychology, MULTI-COUNTRY TEST, adult, COVID-19, female, humans, male, emotional regulation, emotions, Anxiety, Female, COGNITIVE REAPPRAISAL, Psychological resilience, medicine.symptom, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Clinical psychology, Adult, Social Psychology, media_common.quotation_subject, Experimental and Cognitive Psychology, Article, 050105 experimental psychology, Cognitive reappraisal, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Human behaviour, medicine, Humans, 0501 psychology and cognitive sciences, METAANALYSIS, Behaviour Change and Well-being, pandemic, reappraisal, RESILIENCE, NEGATIVE AFFECT, Mental health, Emotional Regulation, REGULATION STRATEGIES, 030217 neurology & neurosurgery
Abstract

© The Author(s), under exclusive licence to Springer Nature Limited 2021, corrected publication 2022, The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world., This project was supported by funds from: the Amazon Web Services (AWS) Imagine Grant (to E.M.B.); the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (JSPS KAKENHI; 16h03079, 17h00875, 18k12015, and 20h04581 to Y.Y.); the research programme Dipartimenti di Eccellenza from the Ministry of Education University and Research (MIUR to N. Cellini and G.M. and the Department of General Psychology of the University of Padua); statutory funds of the University of Wroclaw (to A. Sorokowska); the Charles University Research Programme PROGRES (Q18 to M. Vranka); the Knut and Alice Wallenberg Foundation (2016:0229 to J.K.O.); the Rubicon Grant (019.183sg.007 to K.v.S.) from the Netherlands Organisation for Scientific Research; the Australian Research Council (dp180102384 to R.M.R.); the US National Institutes of Health (NIMH111640 to M.N.-D.), the Huo Family Foundation to N.J.; the NSF Directorate for Social, Behavioral and Economic Sciences, Division of Social and Economic Sciences (1559511 to J.S.L.); the US National Institutes of Health (RO1-CA-224545 to J.S.L.); Eesti Teadusagentuur–Estonian Research Council (PSG525 to A. Uusberg); the J. William Fulbright Program (to F. Azevedo); the HSE Basic Research Program (to D. Dubrov); Dominican University (a Faculty Development Grant to A. Krafnick); and the French National Research Agency Investissements d’avenir supporting PSF (ANR-15-IDEX-02 to H.I.); the Slovak Research and Development Agency (project no. APVV-20-0319 to M. Adamkovič); the programme FUTURE LEADER of Lorraine Université d’Excellence within the French National Research Agency Investissements d’avenir (ANR-15-IDEX-04-LUE to S.M.). Computation for this research was assisted by: the Harvard Business School compute cluster (HBSGrid); and the Open Science Grid. The Open Science Grid is supported by the National Science Foundation award 1148698 and the US Department of Energy’s Office of Science, as well as by the compute resources and assistance of the UW-Madison Center For High Throughput Computing (CHTC) in the Department of Computer Sciences. The CHTC is supported by UW-Madison, the Advanced Computing Initiative, the Wisconsin Alumni Research Foundation, the Wisconsin Institutes for Discovery, and the National Science Foundation, and is an active member of the Open Science Grid, which is supported by the National Science Foundation and the U.S. Department of Energy’s Office of Science.

Published
2021

35. Hydroxylated Chalcones as Aryl Hydrocarbon Receptor Agonists: Structure-Activity Effects

Author

Phanourios Tamamis, Keshav Karki, Stephen Safe, Robert S. Chapkin, Farrhin Nowshad, Laurie A. Davidson, Hyejin Park, Un-Ho Jin, Asuka A. Orr, Arul Jayaraman, and Clinton D. Allred

Subjects
Molecular, Biochemical, and Systems Toxicology, 0301 basic medicine, Polychlorinated Dibenzodioxins, CYP1B1, Cell, Toxicology, digestive system, Mice, 03 medical and health sciences, chemistry.chemical_compound, Chalcones, 0302 clinical medicine, Gene expression, Cytochrome P-450 CYP1A1, medicine, Ethoxyresorufin O-Deethylase, Animals, Humans, Gene, biology, Chemistry, respiratory system, Aryl hydrocarbon receptor, In vitro, 030104 developmental biology, medicine.anatomical_structure, Receptors, Aryl Hydrocarbon, Biochemistry, 030220 oncology & carcinogenesis, Cytochrome P-450 CYP1B1, biology.protein, Caco-2 Cells, DNA, Protein Binding
Abstract

Hydroxylated chalcones are phytochemicals which are biosynthetic precursors of flavonoids and their 1,3-diaryl-prop-2-en-1-one structure is used as a scaffold for drug development. In this study, the structure-dependent activation of aryl hydrocarbon receptor (AhR)-responsive CYP1A1, CYP1B1, and UGT1A1 genes was investigated in Caco2 colon cancer cells and in non-transformed young adult mouse colonocytes (YAMC) cells. The effects of a series of di- and trihydroxychalcones as AhR agonists was structure dependent with maximal induction of CYP1A1, CYP1B1, and UGT1A1 in Caco2 cells observed for compounds containing 2,2′-dihydroxy substituents and this included 2,2′-dihydroxy-, 2,2′,4′-trihydroxy-, and 2,2′,5′-trihydroxychalcones. In contrast, 2′,4,5′-, 2′3′,4′-, 2′,4,4′-trihydroxy, and 2′,3-, 2′,4-, 2′,4′-, and 2′,5-dihydroxychalcones exhibited low to non-detectable AhR activity in Caco2 cells. In addition, all of the hydroxychalcones exhibited minimal to non-detectable activity in YAMC cells, whereas 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced CYP1A1, CYP1B1, and UGT1A1 in Caco2 and YAMC cells. The activity of AhR-active chalcones was confirmed by determining their effects in AhR-deficient Caco2 cells. In addition, 2,2′-dihydroxychalcone induced CYP1A1 protein and formation of an AhR-DNA complex in an in vitro assay. Simulation and modeling studies of hydroxylated chalcones confirmed their interactions with the AhR ligand-binding domain and were consistent with their structure-dependent activity as AhR ligands. Thus, this study identifies hydroxylated chalcones as AhR agonists with potential for these phytochemicals to impact AhR-mediated colonic pathways.

Published
2020

36. 'Big Ideas' of Introductory Chemistry and Biology Courses and the Connections between Them

Author

Zahilyn D. Roche Allred, Laura Santiago Caobi, Brittney Pardinas, Andrea Echarri-Gonzalez, Kathryn P. Kohn, Alex T. Kararo, Melanie M. Cooper, and Sonia M. Underwood

Subjects
Knowledge, Humans, Learning, Students, Biology, General Biochemistry, Genetics and Molecular Biology, Problem Solving, Education
Abstract

Introductory courses are often designed to cover a range of topics with the intent to offer students exposure to the given discipline as preparation to further their study in the same or related disciplines. Unfortunately, students in these courses are often presented with an overwhelming amount of information that may not support their formation of a usable coherent network of knowledge. In this study we conducted a mixed-method sequential exploratory study with students co-enrolled in General Chemistry II and Introductory Biology I to better understand what students perceived to be the "take-home" messages of these courses (i.e., core ideas) and the connections between these courses. We found that students identified a range of ideas from both courses; further analysis of students' explanations and reasoning revealed that, when students talked about their chemistry ideas, they were more likely to talk about them as having predictive and explanatory power in comparison with reasons provided for their biology big ideas. Furthermore, students identified a number of overlapping ideas between their chemistry and biology courses, such as interactions, reactions, and structures, which have the potential to be used as a starting place to support students building a more coherent network of knowledge.

Published
2022

37. Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients

Author

Amanika Kumar, Bahaaeldin Youssef, Yi Lin, Martin J. Cannon, Geraldine V. Vijay, Michael P. Gustafson, Michael A. Strausbauch, Michael C. Deeds, Gretchen E. Glaser, Keith L. Knutson, Courtney L. Erskine, Mary L. Solseth, Matthew S. Block, Allan B. Dietz, Carrie L. Langstraat, Carolyn Klampe, Aminah Jatoi, Kevin D. Pavelko, Andrea E. Wahner-Hendrickson, Kimberly R. Kalli, Megan Grudem, Jacob B. Allred, and S. John Weroha

Subjects
0301 basic medicine, Injections, Intradermal, endocrine system diseases, Science, General Physics and Astronomy, Cancer Vaccines, Transplantation, Autologous, General Biochemistry, Genetics and Molecular Biology, Article, Disease-Free Survival, 03 medical and health sciences, Interferon-gamma, 0302 clinical medicine, Antigen, Immunity, Ovarian cancer, Cytotoxic T cell, Medicine, Humans, Folate Receptor 1, lcsh:Science, Aged, Ovarian Neoplasms, Multidisciplinary, business.industry, Immunogenicity, Interleukin-17, General Chemistry, Dendritic cell, Dendritic Cells, Middle Aged, Cell vaccines, female genital diseases and pregnancy complications, Immunity, Humoral, Transplantation, Vaccination, 030104 developmental biology, 030220 oncology & carcinogenesis, Immunology, Humoral immunity, Th17 Cells, Female, lcsh:Q, Neoplasm Recurrence, Local, business
Abstract

In ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory T cells predict poorer survival. We previously developed a vaccine whereby patient-derived dendritic cells (DCs) are programmed to induce Th17 responses to the OC antigen folate receptor alpha (FRα). Here we report the results of a single-arm open-label phase I clinical trial designed to determine vaccine safety and tolerability (primary outcomes) and recurrence-free survival (secondary outcome). Immunogenicity is also evaluated. Recruitment is complete with a total of 19 Stage IIIC-IV OC patients in first remission after conventional therapy. DCs are generated using our Th17-inducing protocol and are pulsed with HLA class II epitopes from FRα. Mature antigen-loaded DCs are injected intradermally. All patients have completed study-related interventions. No grade 3 or higher adverse events are seen. Vaccination results in the development of Th1, Th17, and antibody responses to FRα in the majority of patients. Th1 and antibody responses are associated with prolonged recurrence-free survival. Antibody-dependent cell-mediated cytotoxic activity against FRα is also associated with prolonged RFS. Of 18 patients evaluable for efficacy, 39% (7/18) remain recurrence-free at the time of data censoring, with a median follow-up of 49.2 months. Thus, vaccination with Th17-inducing FRα-loaded DCs is safe, induces antigen-specific immunity, and is associated with prolonged remission., The folate receptor alpha (FRα) is overexpressed in the majority of high-grade serous ovarian cancers and has been proposed as a candidate vaccine antigen. Here the authors report the safety and immunogenicity of Th17-inducing dendritic cells pulsed with FRα-derived epitopes in an early phase I clinical trial with ovarian cancer patients.

Published
2020

38. Rationale, considerations, and goals for atrial fibrillation centers of excellence

Author

Prashanthan Sanders, Luigi Di Biase, Jose Osorio, Annabelle Santos Volgman, Thomas Deneke, Andrea M. Russo, David J. Slotwiner, Paul D. Varosy, Amber Seiler, Mintu P. Turakhia, Atul Verma, Isabelle C. Van Gelder, Douglas L. Packer, James Allred, Kathryn A. Wood, Thomas F. Deering, Ayman A. Hussein, Suneet Mittal, Andrea Natale, T. Jared Bunch, Jonathan P. Piccini, Mellanie True Hills, Christian T. Ruff, William R. Lewis, and Cardiovascular Centre (CVC)

Subjects
ORAL ANTICOAGULANT-THERAPY, Cost effectiveness, medicine.medical_treatment, media_common.quotation_subject, Center of excellence, Catheter ablation, Quality of life (healthcare), Nursing, Excellence, QUALITY-OF-LIFE, Physiology (medical), Atrial Fibrillation, Humans, Medicine, PREVENTION THERAPY, Societies, Medical, media_common, CATHETER ABLATION, business.industry, GENDER-RELATED DIFFERENCES, Perspective (graphical), SEX-RELATED DIFFERENCES, VS. USUAL CARE, Atrial fibrillation, medicine.disease, Digital health, PATIENT ACTIVATION, STROKE RISK, Cardiology and Cardiovascular Medicine, business, SHARED DECISION-MAKING
Published
2020

39. The NEALS primary lateral sclerosis registry

Author

Sabrina, Paganoni, Fabiola, De Marchi, James, Chan, Sara K, Thrower, Nathan P, Staff, Neil, Datta, Yaz Y, Kisanuki, Vivian, Drory, Christina, Fournier, Erik P, Pioro, Stephen A, Goutman, Nazem, Atassi, Maryangel, Jeon, Sarah, Caldwell, Timothy, Mcdonough, Caroline, Gentile, Jianing, Liu, Michelle, Turner, Carol, Denny, Kevin, Felice, Misty, Green, Stephanie, Scarberry, Saad, Abu-Saleh, Beatrice, Nefussy, Debbie, Hastings, Sangri, Kim, Blake, Swihart, Ximena, Arcila-Londono, Daniel S, Newman, Michael, Silverman, Angela, Genge, Kristiana, Salmon, Lauren, Elman, Leo, Mccluskey, Kelly, Almasy, Marc, Gotkine, Kimberly, Goslin, Arlena, Cummings, Eli K, Edwards, Michael, Rivner, Kristy, Bouchard, Brandy, Quarles, Justin, Kwan, Matthew, Jaffa, Robert, Baloh, Peggy, Allred, David, Walk, Samuel, Maiser, Georgios, Manousakis, Valerie, Ferment, J Americo M, Fernandes, Pariwat, Thaisetthawatkul, Deborah, Heimes, Melissa, Phillips, Laura, Sams, Melissa, Kahler, Alecia, Corcoran, Daniel G, Larriviere, Sadie, Chotto, and Gracy, Juba

Subjects
Adult, medicine.medical_specialty, business.industry, Amyotrophic Lateral Sclerosis, Outcome measures, Neurodegenerative Diseases, Disease, medicine.disease, Upper motor neuron dysfunction, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Neurology, medicine, Humans, Registries, Neurology (clinical), Motor Neuron Disease, Amyotrophic lateral sclerosis, business, 030217 neurology & neurosurgery, Retrospective Studies, Primary Lateral Sclerosis
Abstract

Primary lateral sclerosis (PLS) is a neurodegenerative disease characterized by progressive upper motor neuron dysfunction. Because PLS patients represent only 1 to 4% of patients with adult motor neuron diseases, there is limited information about the disease's natural history. The objective of this study was to establish a large multicenter retrospective longitudinal registry of PLS patients seen at Northeast ALS Consortium (NEALS) sites to better characterize the natural progression of PLS.

Published
2020

40. Concussion-Recovery Trajectories Among Tactical Athletes: Results From the CARE Consortium

Author

Darren E. Campbell, Karen Y. Peck, C. Dain Allred, Megan N. Houston, Brian R. Johnson, Xuming He, Steven P. Broglio, Paul F. Pasquina, Thomas W. McAllister, Steven J. Svoboda, Rachel M Brodeur, Tim F. Kelly, Christopher D’Lauro, Gerald McGinty, Patrick G. O’Donnell, Kenneth L. Cameron, Michael McCrea, Kathryn L. Van Pelt, and Sean K. Meehan

Subjects
Adult, Male, medicine.medical_specialty, Military Health Services, Concussion, Poison control, Physical Therapy, Sports Therapy and Rehabilitation, Context (language use), Asymptomatic, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Clinical Protocols, Injury prevention, medicine, Humans, Orthopedics and Sports Medicine, Brain Concussion, 030222 orthopedics, Duration of Therapy, business.industry, Hazard ratio, Recovery of Function, 030229 sport sciences, General Medicine, medicine.disease, United States, Return to Sport, Athletic Injuries, Cadet, Physical therapy, Female, Symptom Assessment, medicine.symptom, business, Cohort study
Abstract

Context Assessments of the duration of concussion recovery have primarily been limited to sport-related concussions and male contact sports. Furthermore, whereas durations of symptoms and return-to-activity (RTA) protocols encompass total recovery, the trajectory of each duration has not been examined separately. Objective To identify individual (eg, demographics, medical history), initial concussion injury (eg, symptoms), and external (eg, site) factors associated with symptom duration and RTA-protocol duration after concussion. Design Cohort study. Setting Three US military service academies. Patients or Other Participants A total of 10 604 cadets at participating US military service academies enrolled in the study and completed a baseline evaluation and up to 5 postinjury evaluations. A total of 726 cadets (451 men, 275 women) sustained concussions during the study period. Main Outcome Measure(s) Number of days from injury (1) until the participant became asymptomatic and (2) to complete the RTA protocol. Results Varsity athlete cadets took less time than nonvarsity cadets to become asymptomatic (hazard ratio [HR] = 1.75, 95% confidence interval = 1.38, 2.23). Cadets who reported less symptom severity on the Sport Concussion Assessment Tool, third edition (SCAT3), within 48 hours of concussion had 1.45 to 3.77 times shorter symptom-recovery durations than those with more symptom severity. Similar to symptom duration, varsity status was associated with a shorter RTA-protocol duration (HR = 1.74, 95% confidence interval = 1.34, 2.25), and less symptom severity on the SCAT3 was associated with a shorter RTA-protocol duration (HR range = 1.31 to 1.47). The academy that the cadet attended was associated with the RTA-protocol duration (P < .05). Conclusions The initial total number of symptoms reported and varsity athlete status were strongly associated with symptom and RTA-protocol durations. These findings suggested that external (varsity status and academy) and injury (symptom burden) factors influenced the time until RTA.

Published
2020

41. Human land uses reduce climate connectivity across North America

Author

Sean A. Parks, Brady W. Allred, Carlos Carroll, and Solomon Z. Dobrowski

Subjects
Conservation planning, Conservation of Natural Resources, Global and Planetary Change, Ecology, Land use, Resistance (ecology), business.industry, Climate Change, Environmental resource management, Climate change, Multiple factors, Geography, Human exposure, North America, Humans, Environmental Chemistry, Human Activities, Protected area, business, Ecosystem, General Environmental Science
Abstract

Climate connectivity, the ability of a landscape to promote or hinder the movement of organisms in response to a changing climate, is contingent on multiple factors including the distance organisms need to move to track suitable climate over time (i.e. climate velocity) and the resistance they experience along such routes. An additional consideration which has received less attention is that human land uses increase resistance to movement or alter movement routes and thus influence climate connectivity. Here we evaluate the influence of human land uses on climate connectivity across North America by comparing two climate connectivity scenarios, one considering climate change in isolation and the other considering climate change and human land uses. In doing so, we introduce a novel metric of climate connectivity, 'human exposure', that quantifies the cumulative exposure to human activities that organisms may encounter as they shift their ranges in response to climate change. We also delineate potential movement routes and evaluate whether the protected area network supports movement corridors better than non-protected lands. We found that when incorporating human land uses, climate connectivity decreased; climate velocity increased on average by 0.3 km/year and cumulative climatic resistance increased for ~83% of the continent. Moreover, ~96% of movement routes in North America must contend with human land uses to some degree. In the scenario that evaluated climate change in isolation, we found that protected areas do not support climate corridors at a higher rate than non-protected lands across North America. However, variability is evident, as many ecoregions contain protected areas that exhibit both more and less representation of climate corridors compared to non-protected lands. Overall, our study indicates that previous evaluations of climate connectivity underestimate climate change exposure because they do not account for human impacts.

Published
2020

42. Randomized Phase II Trial and Tumor Mutational Spectrum Analysis from Cabozantinib versus Chemotherapy in Metastatic Uveal Melanoma (Alliance A091201)

Author

Jason J. Luke, Gary K. Schwartz, David Hogg, Bruno R. Bastos, Carrie Strand, Daniel J Olson, Timothy Carll, Yuanyuan Zha, Pamela N. Munster, Marcus O. Butler, Jacob B. Allred, Riyue Bao, and Brian W. Labadie

Subjects
Uveal Neoplasms, Male, 0301 basic medicine, Oncology, Cancer Research, Pyridines, medicine.medical_treatment, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Anilides, Neoplasm Metastasis, Melanoma, Cancer, Aged, 80 and over, Tumor, Common Terminology Criteria for Adverse Events, Middle Aged, Dacarbazine, 6.1 Pharmaceuticals, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Cabozantinib, Clinical Trials and Supportive Activities, Oncology and Carcinogenesis, Article, 03 medical and health sciences, Rare Diseases, Clinical Research, Internal medicine, Exome Sequencing, Biomarkers, Tumor, Temozolomide, Genetics, medicine, Humans, Oncology & Carcinogenesis, Survival rate, Aged, Chemotherapy, business.industry, Receptor Protein-Tyrosine Kinases, Evaluation of treatments and therapeutic interventions, medicine.disease, Clinical trial, 030104 developmental biology, chemistry, Mutation, business, Biomarkers
Abstract

Purpose: The surface receptor MET is highly expressed on primary uveal melanoma; MET inhibitors demonstrated early clinical signals of efficacy in slowing uveal melanoma growth. The primary objective of our study was to compare the progression-free survival rate at 4 months (PFS4) of patients with uveal melanoma treated with cabozantinib or chemotherapy. Patients and Methods: Patients with metastatic uveal melanoma and RECIST measurable disease were randomized 2:1 to receive either cabozantinib (arm 1) versus temozolomide or dacarbazine (arm 2) with restaging imaging every two cycles. Cross-over from arm 2 to cabozantinib after progression was allowed (arm 2X). Available tumor specimens were analyzed by whole-exome sequencing (WES) and results were correlated with outcome. Results: Forty-six eligible patients were accrued with 31, 15, and 9 in arms 1, 2, and 2X, respectively. Median lines of prior therapy, including hepatic embolization, were two. Rates of PFS4 in arm 1 and arm 2 were 32.3% and 26.7% (P = 0.35), respectively, with median PFS time of 60 and 59 days (P = 0.964; HR = 0.99). Median overall survival (OS) was 6.4 months and 7.3 months (P = 0.580; HR = 1.21), respectively. Grade 3–4 Common Terminology Criteria for Adverse Events were present in 61.3%, 46.7%, and 37.5% in arms 1, 2, and 2X, respectively. WES demonstrated a mean tumor mutational burden of 1.53 mutations/Mb and did not separate OS ≤ or >1 year (P = 0.14). Known mutations were identified by WES and novel mutations were nominated. Conclusions: MET/VEGFR blockade with cabozantinib demonstrated no improvement in PFS but an increase in toxicity relative to temozolomide/dacarbazine in metastatic uveal melanoma.

Published
2020

43. Safety of bloodless autologous stem cell transplantation in Jehovah's Witness patients

Author

Michelle Lua, Noah Merin, Lorraine Alonzo Hernandez, Sara Oliva, Christopher Lopiccolo, Robert Vescio, Ali Reza Rejali, Jose Causin, Patricia VanStrien, Ronald Legaspi, Leticia Uy, Michael Lill, Seda Gharapetian, Robert Lin, Sara Cooper, Mohana Allred, Melissa Leaverton, Margarita Guerrero, Ronald Paquette, Yuliya Linhares, Alyssa Beck, Jennifer Bourke, Rhona Castillo, Muni Rubens, L. Snoussi, Yvette Federizo, and Lorna Dean

Subjects
medicine.medical_specialty, Blood transfusion, Epidemiology, medicine.medical_treatment, Hematopoietic stem cell transplantation, Transplantation, Autologous, Article, Autologous stem-cell transplantation, Blood product, Humans, Medicine, Blood Transfusion, Jehovah's Witnesses, Multiple myeloma, Retrospective Studies, Transplantation, Chemotherapy, business.industry, Hematopoietic Stem Cell Transplantation, Retrospective cohort study, Hematology, medicine.disease, Stem-cell research, Surgery, business
Abstract

Due to the curative potential and improvement in progression-free survival (PFS), high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered the standard of care for several hematologic malignancies, such as multiple myeloma, and lymphomas. ASCT typically involves support with blood product transfusion. Thus, difficulties arise when Jehovah’s Witness patients refuse blood transfusions. In order to demonstrate the safety of performing “bloodless” ASCT (BL-ASCT), we performed a retrospective analysis of 66 Jehovah's Witnesses patients who underwent BL-ASCT and 1114 non-Jehovah’s Witness patients who underwent transfusion-supported ASCT (TF-ASCT) at Cedars-Sinai Medical Center between January 2000 and September 2018. Survival was compared between the two groups. Transplant-related complications, mortality, engraftment time, length of hospital stay, and number of ICU transfers were characterized for the BL-ASCT group. One year survival was found to be 87.9% for both groups (P = 0.92). In the BL-ASCT group, there was one death prior to the 30 days post transplant due to CNS hemorrhage, and one death prior to 100 days due to sepsis. Based on our data, BL-ASCT can be safely performed with appropriate supportive measures, and we encourage community oncologists to promptly refer JW patients for transplant evaluation when ASCT is indicated.

Published
2020

44. Phase 1 trial of Vismodegib and Erlotinib combination in metastatic pancreatic cancer

Author

Luciana L. Almada, Henry C. Pitot, Martin E. Fernandez-Zapico, Donald W. Northfelt, George P. Kim, David L. Marks, Mitesh J. Borad, Yingwei Qi, Alan H. Bryce, Gerardo Colon-Otero, Tanios Bekaii-Saab, Scott H. Okuno, Axel Grothey, Ezequiel J. Tolosa, Wilma L. Lingle, Wen We Ma, Shanique R. Palmer, Maria J. Lamberti, Robert R. McWilliams, Mien Chie Hung, Matthew R. Callstrom, Charles Erlichman, Val J. Lowe, Julian R. Molina, Aminah Jatoi, Angela L. McCleary-Wheeler, Ryan M. Carr, Paul Haluska, Jacob B. Allred, and Thomas C. Smyrk

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Pyridines, Endocrinology, Diabetes and Metabolism, Vismodegib, Antineoplastic Agents, Article, Erlotinib Hydrochloride, 03 medical and health sciences, 0302 clinical medicine, GLI1, Pancreatic cancer, Internal medicine, Biopsy, medicine, Humans, Anilides, Epidermal growth factor receptor, Aged, Aged, 80 and over, Hepatology, medicine.diagnostic_test, biology, business.industry, Gastroenterology, Middle Aged, medicine.disease, Gemcitabine, Desmoplasia, Pancreatic Neoplasms, 030220 oncology & carcinogenesis, biology.protein, Female, 030211 gastroenterology & hepatology, Erlotinib, medicine.symptom, business, Biomarkers, medicine.drug
Abstract

Background/Objectives Interplay between the Hedgehog (HH) and epidermal growth factor receptor (EGFR) pathways modulating the outcome of their signaling activity have been reported in various cancers including pancreatic ductal adenocarcinoma (PDAC). Therefore, simultaneous targeting of these pathways may be clinically beneficial. This Phase I study combined HH and EGFR inhibition in metastatic PDAC patients. Methods Combined effects of HH and EGFR inhibition using Vismodegib and Erlotinib with or without gemcitabine in metastatic solid tumors were assessed by CT. Another cohort of patients with metastatic PDAC was evaluated by FDG-PET and tumor biopsies-derived biomarkers. Results Treatment was well tolerated with the maximum tolerated dose cohort experiencing no grade 4 toxicities though 25% experienced grade 3 adverse effects. Recommended phase II dose of Vismodegib and Erlotinib were each 150 mg daily. No tumor responses were observed although 16 patients achieved stable disease for 2–7 cycles. Paired biopsy analysis before and after first cycle of therapy in PDAC patients showed reduced GLI1 mRNA, phospho-GLI1 and associated HH target genes in all cases. However, only half of the cases showed reduced levels of desmoplasia or changes in fibroblast markers. Most patients had decreased phospho-EGFR levels. Conclusions Vismodegib and Erlotinib combination was well-tolerated although overall outcome in patients with metastatic PDAC was not significantly impacted by combination treatment. Biomarker analysis suggests direct targets inhibition without significantly affecting the stromal compartment. These findings conflict with pre-clinical mouse models, and thus warrant further investigation into how upstream inhibition of these pathways is circumvented in PDAC.

Published
2020

45. Usability Issues in Evidence-Based Psychosocial Interventions and Implementation Strategies: Cross-project Analysis

Author

Emily Friedman, Michael Pullmann, Ryan Allred, Kendra Kamp, Patricia Arean, Sean Munson, Jessica Chen, and Ian Bennett

Subjects
Adult, Adolescent, Mental Disorders, Humans, Health Informatics, Psychosocial Intervention, United States
Abstract

Background People often prefer evidence-based psychosocial interventions (EBPIs) for mental health care; however, these interventions frequently remain unavailable to people in nonspecialty or integrated settings, such as primary care and schools. Previous research has suggested that usability, a concept from human-centered design, could support an understanding of the barriers to and facilitators of the successful adoption of EBPIs and support the redesign of EBPIs and implementation strategies. Objective This study aimed to identify and categorize usability issues in EBPIs and their implementation strategies. Methods We adapted a usability issue analysis and reporting format from a human-centered design. A total of 13 projects supported by the National Institute of Mental Health—funded Accelerating the Reach and Impact of Treatments for Youth and Adults with Mental Illness Center at the University of Washington used this format to describe usability issues for EBPIs and implementation strategies with which they were working. Center researchers used iterative affinity diagramming and coding processes to identify usability issue categories. On the basis of these categories and the underlying issues, we propose heuristics for the design or redesign of EBPIs and implementation strategies. Results The 13 projects reported a total of 90 usability issues, which we categorized into 12 categories, including complex and/or cognitively overwhelming, required time exceeding available time, incompatibility with interventionist preference or practice, incompatibility with existing workflow, insufficient customization to clients/recipients, intervention buy-in (value), interventionist buy-in (trust), overreliance on technology, requires unavailable infrastructure, inadequate scaffolding for client/recipient, inadequate training and scaffolding for interventionists, and lack of support for necessary communication. These issues range from minor inconveniences that affect a few interventionists or recipients to severe issues that prevent all interventionists or recipients in a setting from completing part or all of the intervention. We propose 12 corresponding heuristics to guide EBPIs and implementation strategy designers in preventing and addressing these usability issues. Conclusions Usability issues were prevalent in the studied EBPIs and implementation strategies. We recommend using the lens of usability evaluation to understand and address barriers to the effective use and reach of EBPIs and implementation strategies. International Registered Report Identifier (IRRID) RR2-10.2196/14990

Published
2022

46. Triaxial accelerometer output predicts oxygen uptake in adults with Down syndrome

Author

Poram Choi, Anthony T. Allred, and Stamatis Agiovlasitis

Subjects
Adult, Male, musculoskeletal diseases, medicine.medical_specialty, Down syndrome, business.industry, Rehabilitation, Triaxial accelerometer, Physical activity, Sedentary behavior, Wrist, Accelerometer, medicine.disease, Oxygen uptake, Oxygen, Physical medicine and rehabilitation, Accelerometry, Humans, Medicine, Down Syndrome, Sedentary Behavior, Energy Metabolism, business, human activities
Abstract

This study examined if the relationship between the rate of oxygen uptake (V̇OSixteen adults with DS (10 men) and 19 adults without DS (10 men) performed 12 tasks including physical activities and sedentary behaviors. We measured V̇OFor both hip- and wrist-accelerometers, VM and group significantly predicted V̇OAdults with DS have different V̇O

Published
2019

47. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Priyadarshini Kachroo, Julian Hecker, Bo L. Chawes, Tarunveer S. Ahluwalia, Michael H. Cho, Dandi Qiao, Rachel S. Kelly, Su H. Chu, Yamini V. Virkud, Mengna Huang, Kathleen C. Barnes, Esteban G. Burchard, Celeste Eng, Donglei Hu, Juan C. Celedón, Michelle Daya, Albert M. Levin, Hongsheng Gui, L. Keoki Williams, Erick Forno, Angel C.Y. Mak, Lydiana Avila, Manuel E. Soto-Quiros, Michelle M. Cloutier, Edna Acosta-Pérez, Glorisa Canino, Klaus Bønnelykke, Hans Bisgaard, Benjamin A. Raby, Christoph Lange, Scott T. Weiss, Jessica A. Lasky-Su, Namiko Abe, Goncalo Abecasis, Christine Albert, Nicholette (Nichole) Palmer Allred, Laura Almasy, Alvaro Alonso, Seth Ament, Peter Anderson, Pramod Anugu, Deborah Applebaum-Bowden, Dan Arking, Donna K. Arnett, Allison Ashley-Koch, Stella Aslibekyan, Tim Assimes, Paul Auer, Dimitrios Avramopoulos, John Barnard, Kathleen Barnes, R. Graham Barr, Emily Barron-Casella, Terri Beaty, Diane Becker, Lewis Becker, Rebecca Beer, Ferdouse Begum, Amber Beitelshees, Emelia Benjamin, Marcos Bezerra, Larry Bielak, Joshua Bis, Thomas Blackwell, John Blangero, Eric Boerwinkle, Ingrid Borecki, Russell Bowler, Jennifer Brody, Ulrich Broeckel, Jai Broome, Karen Bunting, Esteban Burchard, Jonathan Cardwell, Cara Carty, Richard Casaburi, James Casella, Mark Chaffin, Christy Chang, Daniel Chasman, Sameer Chavan, Bo-Juen Chen, Wei-Min Chen, Yii-Der Ida Chen, Seung Hoan Choi, Lee-Ming Chuang, Mina Chung, Elaine Cornell, Adolfo Correa, Carolyn Crandall, James Crapo, L. Adrienne Cupples, Joanne Curran, Jeffrey Curtis, Brian Custer, Coleen Damcott, Dawood Darbar, Sayantan Das, Sean David, Colleen Davis, Mariza de Andrade, Michael DeBaun, Ranjan Deka, Dawn DeMeo, Scott Devine, Ron Do, Qing Duan, Ravi Duggirala, Peter Durda, Susan Dutcher, Charles Eaton, Lynette Ekunwe, Patrick Ellinor, Leslie Emery, Charles Farber, Leanna Farnam, Tasha Fingerlin, Matthew Flickinger, Myriam Fornage, Nora Franceschini, Mao Fu, Stephanie M. Fullerton, Lucinda Fulton, Stacey Gabriel, Weiniu Gan, Yan Gao, Margery Gass, Bruce Gelb, Xiaoqi (Priscilla) Geng, Soren Germer, Chris Gignoux, Mark Gladwin, David Glahn, Stephanie Gogarten, Da-Wei Gong, Harald Goring, C. Charles Gu, Yue Guan, Xiuqing Guo, Jeff Haessler, Michael Hall, Daniel Harris, Nicola Hawley, Jiang He, Ben Heavner, Susan Heckbert, Ryan Hernandez, David Herrington, Craig Hersh, Bertha Hidalgo, James Hixson, John Hokanson, Kramer Holly, Elliott Hong, Karin Hoth, Chao (Agnes) Hsiung, Haley Huston, Chii Min Hwu, Marguerite Ryan Irvin, Rebecca Jackson, Deepti Jain, Cashell Jaquish, Min A. Jhun, Jill Johnsen, Andrew Johnson, Craig Johnson, Rich Johnston, Kimberly Jones, Hyun Min Kang, Robert Kaplan, Sharon Kardia, Sekar Kathiresan, Laura Kaufman, Shannon Kelly, Eimear Kenny, Michael Kessler, Alyna Khan, Greg Kinney, Barbara Konkle, Charles Kooperberg, Stephanie Krauter, Ethan Lange, Leslie Lange, Cathy Laurie, Cecelia Laurie, Meryl LeBoff, Seunggeun Shawn Lee, Wen-Jane Lee, Jonathon LeFaive, David Levine, Dan Levy, Joshua Lewis, Yun Li, Honghuang Lin, Keng Han Lin, Simin Liu, Yongmei Liu, Ruth Loos, Steven Lubitz, Kathryn Lunetta, James Luo, Michael Mahaney, Barry Make, Ani Manichaikul, JoAnn Manson, Lauren Margolin, Lisa Martin, Susan Mathai, Rasika Mathias, Patrick McArdle, Merry-Lynn McDonald, Sean McFarland, Stephen McGarvey, Hao Mei, Deborah A. Meyers, Julie Mikulla, Nancy Min, Mollie Minear, Ryan L. Minster, Braxton Mitchell, May E. Montasser, Solomon Musani, Stanford Mwasongwe, Josyf C. Mychaleckyj, Girish Nadkarni, Rakhi Naik, Pradeep Natarajan, Sergei Nekhai, Deborah Nickerson, Kari North, Jeff O'Connell, Tim O'Connor, Heather Ochs-Balcom, James Pankow, George Papanicolaou, Margaret Parker, Afshin Parsa, Sara Penchev, Juan Manuel Peralta, Marco Perez, James Perry, Ulrike Peters, Patricia Peyser, Lawrence S. Phillips, Sam Phillips, Toni Pollin, Wendy Post, Julia Powers Becker, Meher Preethi Boorgula, Michael Preuss, Dmitry Prokopenko, Bruce Psaty, Pankaj Qasba, Zhaohui Qin, Nicholas Rafaels, Laura Raffield, Vasan Ramachandran, D.C. Rao, Laura Rasmussen-Torvik, Aakrosh Ratan, Susan Redline, Robert Reed, Elizabeth Regan, Alex Reiner, Ken Rice, Stephen Rich, Dan Roden, Carolina Roselli, Jerome Rotter, Ingo Ruczinski, Pamela Russell, Sarah Ruuska, Kathleen Ryan, Phuwanat Sakornsakolpat, Shabnam Salimi, Steven Salzberg, Kevin Sandow, Vijay Sankaran, Christopher Scheller, Ellen Schmidt, Karen Schwander, David Schwartz, Frank Sciurba, Christine Seidman, Jonathan Seidman, Vivien Sheehan, Amol Shetty, Aniket Shetty, Wayne Hui-Heng Sheu, M. Benjamin Shoemaker, Brian Silver, Edwin Silverman, Jennifer Smith, Josh Smith, Nicholas Smith, Tanja Smith, Sylvia Smoller, Beverly Snively, Tamar Sofer, Nona Sotoodehnia, Adrienne Stilp, Elizabeth Streeten, Yun Ju Sung, Jessica Su-Lasky, Jody Sylvia, Adam Szpiro, Carole Sztalryd, Daniel Taliun, Hua Tang, Margaret Taub, Kent Taylor, Simeon Taylor, Marilyn Telen, Timothy A. Thornton, Lesley Tinker, David Tirschwell, Hemant Tiwari, Russell Tracy, Michael Tsai, Dhananjay Vaidya, Peter VandeHaar, Scott Vrieze, Tarik Walker, Robert Wallace, Avram Walts, Emily Wan, Fei Fei Wang, Karol Watson, Daniel E. Weeks, Bruce Weir, Scott Weiss, Lu-Chen Weng, Cristen Willer, Kayleen Williams, Carla Wilson, James Wilson, Quenna Wong, Huichun Xu, Lisa Yanek, Ivana Yang, Rongze Yang, Norann Zaghloul, Maryam Zekavat, Yingze Zhang, Snow Xueyan Zhao, Wei Zhao, Xiuwen Zheng, Degui Zhi, Xiang Zhou, Michael Zody, and Sebastian Zoellner

Subjects
Adult, Costa Rica, Male, Pulmonary and Respiratory Medicine, Adolescent, Vital Capacity, Single-nucleotide polymorphism, Pedigree chart, Critical Care and Intensive Care Medicine, Young Adult, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Polymorphism (computer science), Forced Expiratory Volume, Humans, Medicine, SNP, 030212 general & internal medicine, Child, Asthma, Whole Genome Sequencing, business.industry, Middle Aged, respiratory system, medicine.disease, respiratory tract diseases, Minor allele frequency, 030228 respiratory system, Genetic epidemiology, Child, Preschool, Interferon Regulatory Factors, Immunology, Respiratory Physiological Phenomena, Female, Cardiology and Cardiovascular Medicine, business, Cell Adhesion Molecules
Abstract

BACKGROUND: Asthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma. METHODS: WGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician’s diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes. RESULTS: A genome-wide significant association was identified between baseline FEV(1)/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10(−8) in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10(−6)). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV(1) (P = 3.3 × 10(−3)), postbronchodilator (PB) FEV(1) (7.3 × 10(−3)), and PB FEV(1)/FVC ratio (P = 2.7 × 10(−3)). The identified baseline FEV(1)/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR. CONCLUSIONS: These findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

Published
2019

48. Tooth Wear in Patients Undergoing Sleep Studies: A Blinded Observational Study

Author

Ryan, Allred, David, Shaha, Lowell, Stanford, and Thomas, Beltran

Subjects
Sleep Apnea, Obstructive, Polysomnography, Humans, Tooth Wear, Sleep, Retrospective Studies
Abstract

Obstructive sleep apnea (OSA) is a common health problem that remains an underdiagnosed issue. Screening tools and clinical markers are needed from a variety of providers to determine patients at risk for OSA. Tooth wear could be a good potential identifier of patients at risk of having OSA.This is an ambidirectional observational cohort. Participants were identified as retrospectively having undergone a sleep study and then tooth wear data was prospectively collected at patients' annual dental exam. The participants also completed an anonymous questionnaire to determine correlations with possible confounding factors.A total of 107 individuals were included in the analyses. No significant differences in wear were found between participants with an Apnea-Hypopnea Index (AHI) less than 5 and those with AHI ≥ 5 for any of the teeth examined (all P0.05). Overall, both groups had median tooth wear scores of 2 (IQR 1). Similarly, no differences in tooth wear were found between participants based on their body mass index (BMI) classification or consumption data (all P0.05).Sleep is a complicated entity with many possible confounding factors. There is no correlation between AHI and tooth wear in the selected military cohort. Dentists should screen patients for possible medical and dental conditions whenever tooth wear is detected. Further research is needed to determine if tooth wear could be used as a potential identifier of patients at risk for OSA.

Published
2021

49. Kidney Disease, Hypertension Treatment, and Cerebral Perfusion and Structure

Author

Manjula Kurella Tamura, Sarah Gaussoin, Nicholas M. Pajewski, Greg Zaharchuk, Barry I. Freedman, Stephen R. Rapp, Alexander P. Auchus, William E. Haley, Suzanne Oparil, Jessica Kendrick, Christianne L. Roumie, Srinivasan Beddhu, Alfred K. Cheung, Jeff D. Williamson, John A. Detre, Sudipto Dolui, R. Nick Bryan, Ilya M. Nasrallah, Paul Whelton, Karen C. Johnson, Joni Snyder, Diane Bild, Denise Bonds, Nakela Cook, Jeffrey Cutler, Lawrence Fine, Peter Kaufmann, Paul Kimmel, Lenore Launer, Claudia Moy, William Riley, Laurie Ryan, Eser Tolunay, Song Yang, David Reboussin, Jeff Williamson, Walter T. Ambrosius, William Applegate, Greg Evans, Capri Foy, Dalane Kitzman, Mary Lyles, Nick Pajewski, Steve Rapp, Scott Rushing, Neel Shah, Kaycee M. Sink, Mara Vitolins, Lynne Wagenknecht, Valerie Wilson, Letitia Perdue, Nancy Woolard, Tim Craven, Katelyn Garcia, Laura Lovato, Jill Newman, James Lovato, Lingyi Lu, Chris McLouth, Greg Russell, Bobby Amoroso, Patty Davis, Jason Griffin, Darrin Harris, Mark King, Kathy Lane, Wes Roberson, Debbie Steinberg, Donna Ashford, Phyllis Babcock, Dana Chamberlain, Vickie Christensen, Loretta Cloud, Christy Collins, Delilah Cook, Katherine Currie, Debbie Felton, Stacy Harpe, Marjorie Howard, Michelle Lewis, Pamela Nance, Nicole Puccinelli-Ortega, Laurie Russell, Jennifer Walker, Brenda Craven, Candace Goode, Margie Troxler, Janet Davis, Sarah Hutchens, Anthony A. Killeen, Anna M. Lukkari, Robert Ringer, Brandi Dillard, Norbert Archibeque, Stuart Warren, Mike Sather, James Pontzer, Zach Taylor, Elsayed Z. Soliman, Zhu-Ming Zhang, Yabing Li, Chuck Campbell, Susan Hensley, Julie Hu, Lisa Keasler, Mary Barr, Tonya Taylor, Christos Davatzikos, Ilya Nasarallah, Lisa Desiderio, Mark Elliott, Ari Borthakur, Harsha Battapady, Guray Erus, Alex Smith, Ze Wang, Jimit Doshi, Jackson T. Wright, Mahboob Rahman, Alan J. Lerner, Carolyn Still, Alan Wiggers, Sara Zamanian, Alberta Bee, Renee Dancie, George Thomas, Martin Schreiber, Sankar Dass Navaneethan, John Hickner, Michael Lioudis, Michelle Lard, Susan Marczewski, Jennifer Maraschky, Martha Colman, Andrea Aaby, Stacey Payne, Melanie Ramos, Carol Horner, Paul Drawz, Pratibha P. Raghavendra, Scott Ober, Ronda Mourad, Muralidhar Pallaki, Peter Russo, Pratibha Raghavendra, Pual Fantauzzo, Lisa Tucker, Bill Schwing, John R. Sedor, Edward J. Horwitz, Jeffrey R. Schellling, John F. O’Toole, Lisa Humbert, Wendy Tutolo, Suzanne White, Alishea Gay, Walter Clark, Robin Hughes, Mirela Dobre, Carolyn H. Still, Monique Williams, Udayan Bhatt, Lee Hebert, Anil Agarwal, Melissa Brown Murphy, Nicole Ford, Cynthia Stratton, Jody Baxter, Alicia A. Lykins, Alison McKinley Neal Leena Hirmath, Osei Kwame, Kyaw Soe, William F. Miser, Colleen Sagrilla, Jan Johnston, Amber Anaya, Ashley Mintos, Angel A. Howell, Kelly Rogers, Sara Taylor, Donald Ebersbacher, Lucy Long, Beth Bednarchik, Adrian Schnall, Jonathan Smith, Lori Peysha, Lisa Leach, Megan Tribout, Carla Harwell, Pinkie Ellington, Mary Ann Banerji, Pranav Ghody, Melissa Vahídeh Rambaud, Raymond Townsend, Debbie Cohen, Yonghong Huan, Mark Duckworth, Virginia Ford, Juliet Leshner, Ann Davison, Sarah Vander Veen, Crystal A. Gadegbeku, Avi Gillespie, Anuradha Paranjape, Sandra Amoroso, Zoe Pfeffer, Sally B. Quinn, Jiang He, Jing Chen, Eva Lustigova, Erin Malone, Marie Krousel-Wood, Richard Deichmann, Patricia Ronney, Susan Muery, Donnalee Trapani, Michael Rocco, David Goff, Carlos Rodriguez, Laura Coker, Amret Hawfield, Joseph Yeboah, Lenore Crago, John Summerson, Anita Hege, Matt Diamond, Laura Mulloy, Marcela Hodges, Michelle Collins, Charlene Weathers, Heather Anderson, Emily Stone, Walida Walker, Andrew McWilliams, Michael Dulin, Lindsay Kuhn, Susan Standridge, Lindsay Lowe, Kelly Everett, Kelry Preston, Susan Norton, Silena Gaines, Ali A. Rizvi, Andrew W. Sides, Diamond Herbert, Matthew M. Hix, Melanie Whitmire, Brittany Arnold, Philip Hutchinson, Joseph Espiritu, Mark Feinglos, Eugene Kovalik, Georgianne Gedon-Lipscomb, Kathryn Evans, Connie Thacker, Ronna Zimmer, Mary Furst, MaryAnn Mason, James Powell, Paul Bolin, Junhong Zhang, Mary Pinion, Gail Davis, Winifred Bryant, Presley Phelps, Connie Garris-Sutton, Beatrice Atkinson, Gabriele Contreras, Maritza Suarez, Ivonne Schulman, Don Koggan, Jackie Vassallo, Gloria Peruyera, Sheri Whittington, Cassandra Bethea, Laura Gilliam, Carolyn Pedley, Geraldine Zurek, Miriam Baird, Charles Herring, Mary Martha Smoak, Julie Williams, Samantha Rogers, Lindsay Gordon, Erin Kennedy, Beverly Belle, Jessica McCorkle-Doomy, Jonathan Adams, Ramon Lopez, Juris Janavs, Frederic Rahbari-Oskoui, Arlene Chapman, Allen Dollar, Olubunmi Williams, Yoosun Han, William Haley, Peter Fitzpatrick, Joseph Blackshear, Brian Shapiro, Anna Harrell, Arta Palaj, Katelyn Henderson, Ashley Johnson, Heath Gonzalez, Jermaine Robinson, Leonardo Tamariz, Jennifer Denizard, Rody Barakat, Dhurga Krishnamoorthy, Frank Greenway, Ron Monce, Timothy Church, Chelsea Hendrick, Aimee Yoches, Leighanne Sones, Markee Baltazar, Priscilla Pemu, Connie Jones, Derrick Akpalu, Gordon Chelune, Jeffrey Childs, Lisa Gren, Anne Randall, Laura Dember, Denise Soares, Jerry Yee, Kausik Umanath, Naima Ogletree, Schawana Thaxton, Karen Campana, Dayna Sheldon, Krista MacArthur, J. Brent Muhlestein, Nathan Allred, Brian Clements, Ritesh Dhar, Kent Meredith, Viet Le, Edward Miner, James Orford, Erik R. Riessen, Becca Ballantyne, Ben Chisum, Kevin Johnson, Dixie Peeler, Glenn Chertow, Manju Tamura, Tara Chang, Kevin Erickson, Jenny Shen, Randall S. Stafford, Gregory Zaharchuk, Margareth Del Cid, Michelle Dentinger, Jennifer Sabino, Rukmani Sahay, Ekaterina Telminova, Daniel E. Weiner, Mark Sarnak, Lily Chan, Amanda Civiletto, Alyson Heath, Amy Kantor, Priyanka Jain, Bethany Kirkpatrick, Andrew Well, Barry Yuen, Michel Chonchol, Beverly Farmer, Heather Farmer, Carol Greenwald, Mikaela Malaczewski, James Lash, Anna Porter, Ana Ricardo, Robert T. Rosman, Janet Cohan, Nieves Lopez Barrera, Daniel Meslar, Patricia Meslar, Margaret Conroy, Mark Unruh, Rachel Hess, Manisha Jhamb, Holly Thomas, Pam Fazio, Elle Klixbull, Melissa Komlos-Weimer, LeeAnne Mandich, Tina Vita, Robert Toto, Peter Van Buren, Julia Inrig, Martha Cruz, Tammy Lightfoot, Nancy Wang, Lori Webster, Kalani Raphael, Barry Stults, Tahir Zaman, Debra Simmons, Tooran Lavasani, Rebecca Filipowicz, Guo Wei, Gracie Mary Miller, Jenice Harerra, Jeff Christensen, Ajay Giri, Xiaorui Chen, Natalie Anderton, Arianna Jensen, Julia Lewis, Anna Burgner, Jamie P. Dwyer, Gerald Schulman, Terri Herrud, Ewanda Leavell, Tiffany McCray, Edwina McNeil-Simaan, Munmun Poudel, Malia Reed, Mohammed Sika, Delia Woods, Janice L. Zirkenbach, Dominic S. Raj, Scott Cohen, Samir Patel, Manuel Velasquez, Roshni S. Bastian, Maria Wing, Akshay Roy-Chaudhury, Thomas Depner, Lorien Dalyrymple, George Kaysen, Susan Anderson, John Nord, Joachim H. Ix, Leonard Goldenstein, Cynthia M. Miracle, Nketi Forbang, Maja Mircic, Brenda Thomas, Tiffany Tran, Anjay Rastogi, Mihae Kim, Mohamad Rashid, Bianca Lizarraga, Amy Hocza, Kristine Sarmosyan, Jason Norris, Tushar Sharma, Amanda Chioy, Eric Bernard, Eleanore Cabrera, Christina Lopez, Susana Nunez, Joseph Riad, Suzanne Schweitzer, Siran Sirop, Sarah Thomas, Lauren Wada, Holly Kramer, Vinod Bansal, Corliss E. Taylor, Mark S. Segal, Karen L. Hall, Amir Kazory, Lesa Gilbert, Linda Owens, Danielle Poulton, Elaine Whidden, Jocelyn Wiggins, Caroline Blaum, Linda Nyquist, Lillian Min, Tanya Gure, Ruth Lewis, Jennifer Mawby, Eileen Robinson, Cora E. Lewis, Virginia Bradley, David Calhoun, Stephen Glasser, Kim Jenkins, Tom Ramsey, Nauman Qureshi, Karen Ferguson, Sumrah Haider, Mandy James, Christy Jones, Kim Renfroe, April Seay, Carrie Weigart, Denyse Thornley-Brown, Dana Rizik, Bari Cotton, Meredith Fitz-Gerald, Tiffany Grimes, Carolyn Johnson, Sara Kennedy, Chanel Mason, Lesa Rosato-Burson, Robin Willingham, Eric Judd, Tonya Breaux-Shropshire, Felice Cook, Julia Medina, Lama Ghazi, Hemal Bhatt, James Lewis, Roman Brantley, John Brouilette, Jeffrey Glaze, Stephanie Hall, Nancy Hiott, David Tharpe, Spencer Boddy, Catherine Mack, Catherine Womack, Keiko Asao, Beate Griffin, Carol Hendrix, Karen Johnson, Lisa Jones, Chelsea Towers, Henry Punzi, Kathy Cassidy, Kristin Schumacher, Carmen Irizarry, Ilma Colon, Pedro Colon-Ortiz, Pedro J. Colón-Hernández, Orlando J. Carrasquillo-Navarro, Merari Carrasquillo, Nivea Vazquez, Miguel Sosa-Padilla, Alex Cintron-Pinero, Mayra Ayala, Olga Pacheco, Catalina Rivera, Irma Sotomayor-Gonzalez, Jamie Claudio, Jose Lazaro, Migdalia Arce, Lourdes Heres, Alba Perez, Jose Tavarez-Valle, Ferlinda Arocho, Mercedes Torres, Melvaliz Vazquez, Gerard P. Aurigemma, Rebecca Takis-Smith, Julia Andrieni, Noelle Bodkin, Kiran Chaudhary, Paula Hu, John Kostis, Nora Cosgrove, Denise Bankowski, Monica Boleyn, Laurie Casazza, Victoria Giresi, Tosha Patel, Erin Squindo, Yan Wu, Zeb Henson, Marion Wofford, Jessica Lowery, Deborah Minor, Kimberley Harkins, Alexander Auchus, Michael Flessner, Cathy Adair, Jordan Asher, Debbie Loope, Rita Cobb, Reiner Venegas, Thomas Bigger, Natalie Bello, Shunichi Homma, Daniel Donovan, Carlos Lopez-Jimenez, Amilcar Tirado, Asqual Getaneh, Rocky Tang, Sabrina Durant, Mathew Maurer, Sergio Teruya, Stephen Helmke, Julissa Alvarez, Ruth Campbell, Roberto Pisoni, Rachel Sturdivant, Deborah Brooks, Caroline Counts, Vickie Hunt, Lori Spillers, Donald Brautigam, Timothy Kitchen, Timothy Gorman, Jessica Sayers, Sarah Button, June Chiarot, Rosemary Fischer, Melissa Lyon, Maria Resnick, Nicole Hodges, Jennifer Ferreira, William Cushman, Barry Wall, Linda Nichols, Robert Burns, Jennifer Martindale-Adams, Dan Berlowitz, Elizabeth Clark, Sandy Walsh, Terry Geraci, Carol Huff, Linda Shaw, Karen Servilla, Darlene Vigil, Terry Barrett, Mary Ellen Sweeney, Rebecca Johnson, Susan McConnell, Khadijeh Shahid Salles, Francoise Watson, Cheryl Schenk, Laura Whittington, Maxine Maher, Jonathan Williams, Stephen Swartz, Paul Conlin, George Alexis, Rebecca Lamkin, Patti Underwood, Helen Gomes, Clive Rosendorff, Stephen Atlas, Saadat Khan, Waddy Gonzalez, Samih Barcham, Lawrence Kwon, Matar Matar, Anwar Adhami, Jan Basile, Joseph John, Deborah Ham, Hadi Baig, Mohammed Saklayen, Jason Yap, Helen Neff, Carol Miller, Ling Zheng-Phelan, Saib Gappy, Shiva Rau, Arathi Raman, Vicki Berchou, Elizabeth Jones, Erin Olgren, Cynthia Marbury, Michael Yudd, Sithiporn Sastrasinh, Jennine Michaud, Jessica Fiore, Marianne Kutza, Ronald Shorr, Rattana Mount, Helen Dunn, Susan Stinson, Jessica Hunter, Addison Taylor, Jeffery Bates, Catherine Anderson, Kent Kirchner, Jodi Stubbs, Ardell Hinton, Anita Spencer, Santosh Sharma, Thomas Wiegmann, Smita Mehta, Michelle Krause, Kate Dishongh, Richard Childress, Geeta Gyamlani, Atossa Niakan, Cathy Thompson, Janelle Moody, Carolyn Gresham, Jeffrey Whittle, Gary Barnas, Dawn Wolfgram, Heidi Cortese, Jonette Johnson, Christianne Roumie, Adriana Hung, Jennifer Wharton, Kurt Niesner, Lois Katz, Elizabeth Richardson, George Brock, Joanne Holland, Troy Dixon, Athena Zias, Christine Spiller, Penelope Baker, James Felicetta, Shakaib Rehman, Kelli Bingham, Suzanne Watnick, David Cohen, Jessica Weiss, Tera Johnston, Stephen Giddings, Hala Yamout, Andrew Klein, Caroline Rowe, Kristin Vargo, Kristi Waidmann, Vasilios Papademetriou, Jean Pierre Elkhoury, Barbara Gregory, Susan Amodeo, Mary Bloom, Dalia Goldfarb-Waysman, Richard Treger, Mehran Kashefi, Christina Huang, Karen Knibloe, Areef Ishani, Yelena Slinin, Christine Olney, Jacqueline Rust, Paolo Fanti, Christopher Dyer, Shweta Bansal, Monica Dunnam, Lih-Lan Hu, and Perla Zarate-Abbott

Subjects
Male, medicine.medical_specialty, Renal function, Perfusion scanning, Blood Pressure, Article, chemistry.chemical_compound, Internal medicine, medicine, Humans, Cerebral perfusion pressure, Renal Insufficiency, Chronic, Antihypertensive Agents, Aged, Creatinine, business.industry, medicine.disease, Perfusion, Blood pressure, chemistry, Cerebral blood flow, Nephrology, Cerebrovascular Circulation, Hypertension, Albuminuria, Cardiology, Female, medicine.symptom, business, Kidney disease, Glomerular Filtration Rate
Abstract

RATIONALE AND OBJECTIVE: The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in those with and without CKD. STUDY DESIGN: Neuroimaging substudy of a randomized trial. SETTING & PARTICIPANTS: A subset of participants in the Systolic Blood Pressure Intervention Trial who underwent brain MRI studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). INTERVENTION: Participants were randomly assigned to intensive (systolic BP 30 mg/g (N=151), the effects of intensive versus standard BP treatment on change in global cerebral blood flow, WMLs and total brain volume were 1.91 ml/100g/min (95% CI −3.01, 6.82), 0.003 cm(3) (asinh transformed, 95% CI −0.13, 0.13), and −7.0 cm(3) (95% CI −13.3, −0.3), respectively. The overall treatment effects on cerebral blood flow and total brain volume were not modified by baseline eGFR or UACR; however the effect on WMLs was attenuated in participants with albuminuria (interaction p-value 0.04). LIMITATIONS: Measurement variability due to multi-site design. CONCLUSIONS: Among hypertensive adults with primarily early kidney disease, intensive versus standard blood pressure treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive blood pressure treatment targets on brain health in persons with early kidney disease. FUNDING: The Systolic Blood Pressure Intervention Trial was funded by the National Institutes of Health (including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke), and this substudy was funded by the National Institutes of Diabetes and Digestive and Kidney Diseases. TRIAL REGISTRATION: SPRINT was registered at ClinicalTrials.gov with the study number NCT01206062.

Published
2021

50. Neonatal Cranial Ultrasound Findings Among Infants Born Extremely Preterm: Associations With Neurodevelopmental Outcomes at Ten Years of Age

Author

Irina L. Mokrova, Jennifer Check, Karl C.K. Kuban, Stephen R. Hooper, Lynn A. Fordham, Elizabeth N. Allred, T. Michael O'Shea, Alan Leviton, Hongyu Ru, Rebecca C. Fry, Hudson P. Santos, Heather Campbell, Nigel Paneth, Hernan Jara, Laurie M. Douglass, Jean A. Frazier, Robert M. Joseph, and Kyle Roell

Subjects
Male, Pediatrics, medicine.medical_specialty, Critical Care, Infant, Premature, Diseases, Article, Cerebral palsy, Cohort Studies, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Leukoencephalopathies, 030225 pediatrics, Medicine, Humans, 030212 general & internal medicine, Cognitive impairment, Child, Cerebral Intraventricular Hemorrhage, business.industry, Extremely preterm, Age Factors, Infant, Newborn, medicine.disease, Echoencephalography, United States, Hospitalization, Cranial ultrasound, Intraventricular hemorrhage, Increased risk, Neurodevelopmental Disorders, Infant, Extremely Premature, Pediatrics, Perinatology and Child Health, Female, business, Birth cohort
Abstract

OBJECTIVE: To examine the association between neonatal cranial ultrasound abnormalities among infants born extremely preterm and neurodevelopmental outcomes at ten years of age. STUDY DESIGN: In a multi-center birth cohort of infants born at < 28 weeks’ gestation, 889 of 1198 survivors were evaluated for neurological, cognitive, and behavioral outcomes at 10 years of age. Sonographic markers of white matter damage (WMD) included echolucencies in the brain parenchyma and moderate to severe ventricular enlargement. Neonatal cranial ultrasound findings were classified as: intraventricular hemorrhage (IVH) without WMD, IVH with WMD, WMD without IVH, and neither IVH nor WMD. RESULTS: WMD without IVH was associated with an increased risk of cognitive impairment (OR 3.5, 95% CI 1.7, 7.4), cerebral palsy (OR 14.3, 95% CI 6.5, 31.5), and epilepsy (OR 6.9; 95% CI 2.9, 16.8). Similar associations were found for WMD accompanied by IVH. Isolated IVH was not significantly associated these outcomes. CONCLUSIONS: Among children born extremely preterm, cranial ultrasound abnormalities, particularly those indicative of WMD, are predictive of neurodevelopmental impairments at 10 years of age. The strongest associations were found with cerebral palsy.

Published
2021

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