Author: "Dennis, J." / Database: OAIster - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Dennis, J."' showing total 2,506 results

Start Over Author "Dennis, J." Database OAIster

2,506 results on '"Dennis, J."'

1. From Targets to Solutions: Implementing a Trauma Quality Improvement Bundle in Cameroon

Author: Zheng, Dennis J, Zheng, Dennis J, Yost, Mark T, Mbuh, Lidwine N, Tchekep, Mirene, Boumsong, Jean Baptiste, Tsiagadigui, Jean Gustave, Oke, Rasheedat, Juillard, Catherine, Chichom-Mefire, Alain, Christie, S Ariane, Zheng, Dennis J, Zheng, Dennis J, Yost, Mark T, Mbuh, Lidwine N, Tchekep, Mirene, Boumsong, Jean Baptiste, Tsiagadigui, Jean Gustave, Oke, Rasheedat, Juillard, Catherine, Chichom-Mefire, Alain, and Christie, S Ariane
Abstract: BackgroundGlobal surgery research efforts have been criticized for failure to transition from problem identification to intervention implementation. We developed a context-appropriate trauma quality improvement (TQI) bundle to ameliorate care gaps at a regional referral hospital in Cameroon. We determined associations between bundle implementation and improvement in trauma resuscitation practices.MethodsWe implemented a TQI bundle consisting of a hospital-specific trauma protocol, staff training, a trauma checklist, provision of essential emergency trauma supplies in the resuscitation area, and monthly quality improvement meetings. We compared trends in target process measures (e.g., frequency and timing of vital sign collection and primary survey interventions) in the six-month period pre- and post-bundle implementation using Wilcoxon rank-sum and Fisher's exact tests.ResultsWe compared 246 pre-bundle patients with 203 post-bundle patients. Post-bundle patients experienced a greater proportion of all vital signs collected compared to the pre-intervention cohort (0 % pre-bundle vs. 69 % post-bundle, p < 0.001); specifically, the proportion of respiratory rate (0.8 % pre-bundle vs. 76 % post-bundle, p < 0.001) and temperature (7 % pre-bundle vs. 91 % post-bundle, p < 0.001) vital sign collection significantly increased. The post-bundle cohort had vital signs measured sooner (74 % vital signs measured within 15 min of arrival pre-bundle vs. 90 % post-bundle, p < 0.001) and more frequently per patient (7 % repeated vitals pre-bundle vs 52 % post-bundle, p < 0.001). Key primary survey interventions such as respiratory interventions (1 % pre-bundle vs. 8 % post-bundle, p < 0.001) and cervical collar placement (0 % pre-bundle vs. 7 % post-bundle, p < 0.001) also increased in the post-bundle cohort.ConclusionsThe implementation of a context-appropriate TQI bundle was associated with significant improvements in previously identified trauma care deficits
Published: 2024

2. Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development

Author: Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, Schwalbe, Harald, Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, and Schwalbe, Harald
Abstract: SARS‐CoV‐2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti‐virals. Within the international Covid19‐NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR‐detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure‐based drug design against the SCoV2 proteome.
Published: 2024

3. Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development

Author: Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, Schwalbe, Harald, Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, and Schwalbe, Harald
Abstract: SARS‐CoV‐2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti‐virals. Within the international Covid19‐NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR‐detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure‐based drug design against the SCoV2 proteome.
Published: 2024

4. Feline Infectious Peritonitis mRNA Vaccine Elicits Both Humoral and Cellular Immune Responses in Mice

Author: Brostoff, Terza, Brostoff, Terza, Savage, Hannah P, Jackson, Kenneth A, Dutra, Joseph C, Fontaine, Justin H, Hartigan-O’Connor, Dennis J, Carney, Randy P, Pesavento, Patricia A, Brostoff, Terza, Brostoff, Terza, Savage, Hannah P, Jackson, Kenneth A, Dutra, Joseph C, Fontaine, Justin H, Hartigan-O’Connor, Dennis J, Carney, Randy P, and Pesavento, Patricia A
Abstract: Feline infectious peritonitis (FIP) is a devastating and often fatal disease caused by feline coronavirus (FCoV). Currently, there is no widely used vaccine for FIP, and many attempts using a variety of platforms have been largely unsuccessful due to the disease's highly complicated pathogenesis. One such complication is antibody-dependent enhancement (ADE) seen in FIP, which occurs when sub-neutralizing antibody responses to viral surface proteins paradoxically enhance disease. A novel vaccine strategy is presented here that can overcome the risk of ADE by instead using a lipid nanoparticle-encapsulated mRNA encoding the transcript for the internal structural nucleocapsid (N) FCoV protein. Both wild type and, by introduction of silent mutations, GC content-optimized mRNA vaccines targeting N were developed. mRNA durability in vitro was characterized by quantitative reverse-transcriptase PCR and protein expression by immunofluorescence assay for one week after transfection of cultured feline cells. Both mRNA durability and protein production in vitro were improved with the GC-optimized construct as compared to wild type. Immune responses were assayed by looking at N-specific humoral (by ELISA) and stimulated cytotoxic T cell (by flow cytometry) responses in a proof-of-concept mouse vaccination study. These data together demonstrate that an LNP-mRNA FIP vaccine targeting FCoV N is stable in vitro, capable of eliciting an immune response in mice, and provides justification for beginning safety and efficacy trials in cats.
Published: 2024

5. Gravidity influences distinct transcriptional profiles of maternal and fetal placental macrophages at term

Author: Ozarslan, Nida, Ozarslan, Nida, Robinson, Joshua F, Buarpung, Sirirak, Kim, M Yvonne, Ansbro, Megan R, Akram, Jason, Montoya, Dennis J, Kamya, Moses R, Kakuru, Abel, Dorsey, Grant, Rosenthal, Philip J, Cheng, Genhong, Feeney, Margaret E, Fisher, Susan J, Gaw, Stephanie L, Ozarslan, Nida, Ozarslan, Nida, Robinson, Joshua F, Buarpung, Sirirak, Kim, M Yvonne, Ansbro, Megan R, Akram, Jason, Montoya, Dennis J, Kamya, Moses R, Kakuru, Abel, Dorsey, Grant, Rosenthal, Philip J, Cheng, Genhong, Feeney, Margaret E, Fisher, Susan J, and Gaw, Stephanie L
Abstract: IntroductionMaternal intervillous monocytes (MIMs) and fetal Hofbauer cells (HBCs) are myeloid-derived immune cells at the maternal-fetal interface. Maternal reproductive history is associated with differential risk of pregnancy complications. The molecular phenotypes and roles of these distinct monocyte/macrophage populations and the influence of gravidity on these phenotypes has not been systematically investigated.MethodsHere, we used RNA sequencing to study the transcriptional profiles of MIMs and HBCs in normal term pregnancies.ResultsOur analyses revealed distinct transcriptomes of MIMs and HBCs. Genes involved in differentiation and cell organization pathways were more highly expressed in MIMs vs. HBCs. In contrast, HBCs had higher expression of genes involved in inflammatory responses and cell surface receptor signaling. Maternal gravidity influenced monocyte programming, as expression of pro-inflammatory molecules was significantly higher in MIMs from multigravidae compared to primigravidae. In HBCs, multigravidae displayed enrichment of gene pathways involved in cell-cell signaling and differentiation.DiscussionOur results demonstrated that MIMs and HBCs have highly divergent transcriptional signatures, reflecting their distinct origins, locations, functions, and roles in inflammatory responses. Furthermore, maternal gravidity influences the gene signatures of MIMs and HBCs, potentially modulating the interplay between tolerance and trained immunity. The phenomenon of reproductive immune memory may play a novel role in the differential susceptibility of primigravidae to pregnancy complications.
Published: 2024

6. Functional network characteristics in anxiety- and mania-based subgroups of bipolar I disorder

Author: Hermans, Adriana P C, Schutter, Dennis J L G, Bethlehem, Richard A I, Hermans, Adriana P C, Schutter, Dennis J L G, and Bethlehem, Richard A I
Abstract: Background: Bipolar disorder I (BD-I) is a heterogeneous disorder with a high prevalence of comorbid anxiety. The aim of this study was to investigate whether anxiety and mania symptoms define distinct subgroups within BD-I and to explore potential differences in functional network characteristics between these subgroups. Methods: Subgroups were identified using scores from clinical anxiety and mania scales. After dimension reduction of these scores, data-driven clustering analysis with cross-validation was employed to reveal the existence of subgroups. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were pre-processed using fMRIPrep. After parcellation and network construction, global and regional graph theoretical measures were calculated per subgroup. Results: Clustering results revealed that, based on anxiety symptomatology, subjects fell into two distinct subgroups, whereas mania symptoms divided subjects into four unique subgroups. These subgroups varied notably on several symptom scales. Network assortativity was significantly associated with anxiety subgroups. Post-hoc pairwise comparisons did not reveal significant global functional network differences between the anxiety subgroups or between mania subgroups. Regional network differences between clinical subgroups were especially apparent for strength and degree in the temporal and frontal lobes. Limitations: Small sample size of some subgroups is a limitation of this study as is the categorical rather than continuous representation of anxiety and mania symptoms. Conclusions: BD-I populations may be stratified into robust subgroups based on anxiety and mania symptoms, showing differences in functional network connectivity. Our findings highlight new avenues of research for investigating heterogeneity in psychiatric populations.
Published: 2024

7. The underestimated fraction : diversity, challenges and novel insights into unicellular cyanobionts of lichens

Author: Jung, Patrick, Briegel-Williams, Laura, Büdel, Burkhard, Schultz, Matthias, Nürnberg, Dennis J., Grube, Martin, D'Agostino, Paul M., Kastovský, Jan, Mares, Jan, Lorenz, Maike, Gil González, Manuel Luis, Dal Forno, Manuela, Westberg, Martin, Chrismas, Nathan, Pietrasiak, Nicole, Whelan, Paul, Dvorak, Petr, Kosuthová, Alica, Gkelis, Spyros, Bauersachs, Thorsten, Schiefelbein, Ulf, Giao, Võ Thi Phi, Lakatos, Michael, Jung, Patrick, Briegel-Williams, Laura, Büdel, Burkhard, Schultz, Matthias, Nürnberg, Dennis J., Grube, Martin, D'Agostino, Paul M., Kastovský, Jan, Mares, Jan, Lorenz, Maike, Gil González, Manuel Luis, Dal Forno, Manuela, Westberg, Martin, Chrismas, Nathan, Pietrasiak, Nicole, Whelan, Paul, Dvorak, Petr, Kosuthová, Alica, Gkelis, Spyros, Bauersachs, Thorsten, Schiefelbein, Ulf, Giao, Võ Thi Phi, and Lakatos, Michael
Abstract: Lichens are remarkable and classic examples of symbiotic organisms that have fascinated scientists for centuries. Yet, it has only been for a couple of decades that significant advances have focused on the diversity of their green algal and/or cyanobacterial photobionts. Cyanolichens, which contain cyanobacteria as their photosynthetic partner, include up to 10% of all known lichens and, as such, studies on their cyanobionts are much rarer compared to their green algal counterparts. For the unicellular cyanobionts, i.e. cyanobacteria that do not form filaments, these studies are even scarcer. Nonetheless, these currently include at least 10 different genera in the cosmopolitan lichen order Lichinales. An international consortium (International Network of CyanoBionts; INCb) will tackle this lack of knowledge. In this article, we discuss the status of current unicellular cyanobiont research, compare the taxonomic resolution of photobionts from cyanolichens with those of green algal lichens (chlorolichens), and give a roadmap of research on how to recondition the underestimated fraction of symbiotic unicellular cyanobacteria in lichens.
Published: 2024
Full Text: View/download PDF

8. The underestimated fraction : diversity, challenges and novel insights into unicellular cyanobionts of lichens

Author: Jung, Patrick, Briegel-Williams, Laura, Büdel, Burkhard, Schultz, Matthias, Nürnberg, Dennis J., Grube, Martin, D'Agostino, Paul M., Kastovský, Jan, Mares, Jan, Lorenz, Maike, Gil González, Manuel Luis, Dal Forno, Manuela, Westberg, Martin, Chrismas, Nathan, Pietrasiak, Nicole, Whelan, Paul, Dvorak, Petr, Kosuthová, Alica, Gkelis, Spyros, Bauersachs, Thorsten, Schiefelbein, Ulf, Giao, Võ Thi Phi, Lakatos, Michael, Jung, Patrick, Briegel-Williams, Laura, Büdel, Burkhard, Schultz, Matthias, Nürnberg, Dennis J., Grube, Martin, D'Agostino, Paul M., Kastovský, Jan, Mares, Jan, Lorenz, Maike, Gil González, Manuel Luis, Dal Forno, Manuela, Westberg, Martin, Chrismas, Nathan, Pietrasiak, Nicole, Whelan, Paul, Dvorak, Petr, Kosuthová, Alica, Gkelis, Spyros, Bauersachs, Thorsten, Schiefelbein, Ulf, Giao, Võ Thi Phi, and Lakatos, Michael
Abstract: Lichens are remarkable and classic examples of symbiotic organisms that have fascinated scientists for centuries. Yet, it has only been for a couple of decades that significant advances have focused on the diversity of their green algal and/or cyanobacterial photobionts. Cyanolichens, which contain cyanobacteria as their photosynthetic partner, include up to 10% of all known lichens and, as such, studies on their cyanobionts are much rarer compared to their green algal counterparts. For the unicellular cyanobionts, i.e. cyanobacteria that do not form filaments, these studies are even scarcer. Nonetheless, these currently include at least 10 different genera in the cosmopolitan lichen order Lichinales. An international consortium (International Network of CyanoBionts; INCb) will tackle this lack of knowledge. In this article, we discuss the status of current unicellular cyanobiont research, compare the taxonomic resolution of photobionts from cyanolichens with those of green algal lichens (chlorolichens), and give a roadmap of research on how to recondition the underestimated fraction of symbiotic unicellular cyanobacteria in lichens.
Published: 2024
Full Text: View/download PDF

9. Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Author: Kentistou, KA, Kaisinger, LR, Stankovic, S, Vaudel, M, Mendes de Oliveira, E, Messina, A, Walters, RG, Liu, X, Busch, AS, Helgason, H, Thompson, DJ, Santoni, F, Petricek, KM, Zouaghi, Y, Huang-Doran, I, Gudbjartsson, DF, Bratland, E, Lin, K, Gardner, EJ, Zhao, Y, Jia, RY, Terao, C, Riggan, MJ, Bolla, MK, Yazdanpanah, M, Yazdanpanah, N, Bradfield, JP, Broer, L, Campbell, A, Chasman, DI, Cousminer, DL, Franceschini, N, Franke, LH, Girotto, G, He, C, Järvelin, M-R, Joshi, PK, Kamatani, Y, Karlsson, R, Luan, J, Lunetta, KL, Mägi, R, Mangino, M, Medland, SE, Meisinger, C, Noordam, R, Nutile, T, Concas, MP, Polašek, O, Porcu, E, Ring, SM, Sala, C, Smith, AV, Tanaka, T, van der Most, PJ, Vitart, V, Wang, CA, Willemsen, G, Zygmunt, M, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Auer, PL, Barnes, CLK, Beckmann, MW, Berrington de Gonzalez, A, Bogdanova, NV, Bojesen, SE, Brenner, H, Buring, JE, Canzian, F, Chang-Claude, J, Couch, FJ, Cox, A, Crisponi, L, Czene, K, Daly, MB, Demerath, EW, Dennis, J, Devilee, P, De Vivo, I, Dörk, T, Dunning, AM, Dwek, M, Eriksson, JG, Fasching, PA, Fernandez-Rhodes, L, Ferreli, L, Fletcher, O, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, González-Neira, A, Grallert, H, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Hakonarson, H, Hart, RJ, Hickey, M, Hooning, MJ, Hoppe, R, Hopper, JL, Hottenga, J-J, Hu, FB, Huebner, H, Hunter, DJ, ABCTB Investigators, Jernström, H, John, EM, Karasik, D, Khusnutdinova, EK, Kristensen, VN, Lacey, JV, Lambrechts, D, Launer, LJ, Lind, PA, Lindblom, A, Magnusson, PKE, Mannermaa, A, McCarthy, MI, Meitinger, T, Menni, C, Michailidou, K, Millwood, IY, Milne, RL, Montgomery, GW, Nevanlinna, H, Nolte, IM, Nyholt, DR, Obi, N, O'Brien, KM, Offit, K, Oldehinkel, AJ, Ostrowski, SR, Palotie, A, Pedersen, OB, Peters, A, Pianigiani, G, Plaseska-Karanfilska, D, Pouta, A, Pozarickij, A, Radice, P, Rennert, G, Rosendaal, FR, Ruggiero, D, Saloustros, E, Sandler, DP, Schipf, S, Schmidt, CO, Schmidt, MK, Small, K, Spedicati, B, Stampfer, M, Stone, J, Tamimi, RM, Teras, LR, Tikkanen, E, Turman, C, Vachon, CM, Wang, Q, Winqvist, R, Wolk, A, Zemel, BS, Zheng, W, van Dijk, KW, Alizadeh, BZ, Bandinelli, S, Boerwinkle, E, Boomsma, DI, Ciullo, M, Chenevix-Trench, G, Cucca, F, Esko, T, Gieger, C, Grant, SFA, Gudnason, V, Hayward, C, Kolčić, I, Kraft, P, Lawlor, DA, Martin, NG, Nøhr, EA, Pedersen, NL, Pennell, CE, Ridker, PM, Robino, A, Snieder, H, Sovio, U, Spector, TD, Stöckl, D, Sudlow, C, Timpson, NJ, Toniolo, D, Uitterlinden, A, Ulivi, S, Völzke, H, Wareham, NJ, Widen, E, Wilson, JF, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group, Pharoah, PDP, Li, L, Easton, DF, Njølstad, PR, Sulem, P, Murabito, JM, Murray, A, Manousaki, D, Juul, A, Erikstrup, C, Stefansson, K, Horikoshi, M, Chen, Z, Farooqi, IS, Pitteloud, N, Johansson, S, Day, FR, Perry, JRB, Ong, KK, Kentistou, KA, Kaisinger, LR, Stankovic, S, Vaudel, M, Mendes de Oliveira, E, Messina, A, Walters, RG, Liu, X, Busch, AS, Helgason, H, Thompson, DJ, Santoni, F, Petricek, KM, Zouaghi, Y, Huang-Doran, I, Gudbjartsson, DF, Bratland, E, Lin, K, Gardner, EJ, Zhao, Y, Jia, RY, Terao, C, Riggan, MJ, Bolla, MK, Yazdanpanah, M, Yazdanpanah, N, Bradfield, JP, Broer, L, Campbell, A, Chasman, DI, Cousminer, DL, Franceschini, N, Franke, LH, Girotto, G, He, C, Järvelin, M-R, Joshi, PK, Kamatani, Y, Karlsson, R, Luan, J, Lunetta, KL, Mägi, R, Mangino, M, Medland, SE, Meisinger, C, Noordam, R, Nutile, T, Concas, MP, Polašek, O, Porcu, E, Ring, SM, Sala, C, Smith, AV, Tanaka, T, van der Most, PJ, Vitart, V, Wang, CA, Willemsen, G, Zygmunt, M, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Auer, PL, Barnes, CLK, Beckmann, MW, Berrington de Gonzalez, A, Bogdanova, NV, Bojesen, SE, Brenner, H, Buring, JE, Canzian, F, Chang-Claude, J, Couch, FJ, Cox, A, Crisponi, L, Czene, K, Daly, MB, Demerath, EW, Dennis, J, Devilee, P, De Vivo, I, Dörk, T, Dunning, AM, Dwek, M, Eriksson, JG, Fasching, PA, Fernandez-Rhodes, L, Ferreli, L, Fletcher, O, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, González-Neira, A, Grallert, H, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Hakonarson, H, Hart, RJ, Hickey, M, Hooning, MJ, Hoppe, R, Hopper, JL, Hottenga, J-J, Hu, FB, Huebner, H, Hunter, DJ, ABCTB Investigators, Jernström, H, John, EM, Karasik, D, Khusnutdinova, EK, Kristensen, VN, Lacey, JV, Lambrechts, D, Launer, LJ, Lind, PA, Lindblom, A, Magnusson, PKE, Mannermaa, A, McCarthy, MI, Meitinger, T, Menni, C, Michailidou, K, Millwood, IY, Milne, RL, Montgomery, GW, Nevanlinna, H, Nolte, IM, Nyholt, DR, Obi, N, O'Brien, KM, Offit, K, Oldehinkel, AJ, Ostrowski, SR, Palotie, A, Pedersen, OB, Peters, A, Pianigiani, G, Plaseska-Karanfilska, D, Pouta, A, Pozarickij, A, Radice, P, Rennert, G, Rosendaal, FR, Ruggiero, D, Saloustros, E, Sandler, DP, Schipf, S, Schmidt, CO, Schmidt, MK, Small, K, Spedicati, B, Stampfer, M, Stone, J, Tamimi, RM, Teras, LR, Tikkanen, E, Turman, C, Vachon, CM, Wang, Q, Winqvist, R, Wolk, A, Zemel, BS, Zheng, W, van Dijk, KW, Alizadeh, BZ, Bandinelli, S, Boerwinkle, E, Boomsma, DI, Ciullo, M, Chenevix-Trench, G, Cucca, F, Esko, T, Gieger, C, Grant, SFA, Gudnason, V, Hayward, C, Kolčić, I, Kraft, P, Lawlor, DA, Martin, NG, Nøhr, EA, Pedersen, NL, Pennell, CE, Ridker, PM, Robino, A, Snieder, H, Sovio, U, Spector, TD, Stöckl, D, Sudlow, C, Timpson, NJ, Toniolo, D, Uitterlinden, A, Ulivi, S, Völzke, H, Wareham, NJ, Widen, E, Wilson, JF, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group, Pharoah, PDP, Li, L, Easton, DF, Njølstad, PR, Sulem, P, Murabito, JM, Murray, A, Manousaki, D, Juul, A, Erikstrup, C, Stefansson, K, Horikoshi, M, Chen, Z, Farooqi, IS, Pitteloud, N, Johansson, S, Day, FR, Perry, JRB, and Ong, KK
Abstract: Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.
Published: 2024

10. Klebsiella LPS O1-antigen prevents complement-mediated killing by inhibiting C9 polymerization

Author: MMB Research line 1, Infection & Immunity, Masson, Frerich M, Káradóttir, Salvör, van der Lans, Sjors P A, Doorduijn, Dennis J, de Haas, Carla J C, Rooijakkers, Suzan H M, Bardoel, Bart W, MMB Research line 1, Infection & Immunity, Masson, Frerich M, Káradóttir, Salvör, van der Lans, Sjors P A, Doorduijn, Dennis J, de Haas, Carla J C, Rooijakkers, Suzan H M, and Bardoel, Bart W
Published: 2024

11. Case fatality and functional outcome after spontaneous subarachnoid haemorrhage: A systematic review and meta-analysis of time trends and regional variations in population-based studies

Author: Neurologen, Brain, Ziebart, Andreas, Dremel, Judith, Hetjens, Svetlana, Nieuwkamp, Dennis J., Linn, Francisca H.H., Etminan, Nima, Rinkel, Gabriel J.E., Neurologen, Brain, Ziebart, Andreas, Dremel, Judith, Hetjens, Svetlana, Nieuwkamp, Dennis J., Linn, Francisca H.H., Etminan, Nima, and Rinkel, Gabriel J.E.
Published: 2024

12. Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development

Author: Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, Schwalbe, Harald, Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, and Schwalbe, Harald
Abstract: SARS‐CoV‐2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti‐virals. Within the international Covid19‐NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR‐detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure‐based drug design against the SCoV2 proteome.
Published: 2024

13. Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development

Author: Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, Schwalbe, Harald, Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, and Schwalbe, Harald
Abstract: SARS‐CoV‐2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti‐virals. Within the international Covid19‐NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR‐detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure‐based drug design against the SCoV2 proteome.
Published: 2024

14. Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development

Author: Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, Schwalbe, Harald, Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, and Schwalbe, Harald
Abstract: SARS‐CoV‐2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti‐virals. Within the international Covid19‐NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR‐detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure‐based drug design against the SCoV2 proteome.
Published: 2024

15. Pharmacokinetics of isavuconazole in healthy cats after oral and intravenous administration.

Author: Woerde, Dennis J, Woerde, Dennis J, Wittenburg, Luke A, Dear, Jonathan D, Woerde, Dennis J, Woerde, Dennis J, Wittenburg, Luke A, and Dear, Jonathan D
Abstract: BackgroundIsavuconazole is a triazole antifungal drug that has shown good efficacy in human patients. Absorption and pharmacokinetics have not been evaluated in cats.ObjectivesTo determine the pharmacokinetics of isavuconazole in cats given a single IV or PO dose.AnimalsEight healthy, adult research cats.MethodsFour cats received 100 mg capsules of isavuconazole PO. Four cats received 5 mg/kg isavuconazole solution IV. Serum was collected at predetermined intervals for analysis using ultra-high performance liquid chromatography-tandem mass spectrometry. Data were analyzed using a 2-compartment uniform weighting pharmacokinetic analysis with lag time for PO administration and a 2 compartment, 1/y2 weighting for IV administration. Predicted 24 and 48-hour dosing intervals of 100 mg isavuconazole administered PO were modeled and in vitro plasma protein binding was assessed.ResultsBoth PO and IV drug administration resulted in high serum concentrations. Intravenous and PO formulations of isavuconazole appear to be able to be used interchangeably. Peak serum isavuconazole concentrations occurred 5 ± 3.8 hours after PO administration with an elimination rate half-life of 66.2 ± 55.3 hours. Intersubject variability was apparent in both the PO and IV groups. Two cats vomited 6 to 8 hours after PO administration. No adverse effects were observed in the IV group. Oral bioavailability was estimated to be approximately 88%. Serum protein binding was calculated to be approximately 99.0% ± 0.03%.Conclusions and clinical importanceIsavuconazole might prove to be useful in cats with fungal disease given its favorable pharmacokinetics. Additional studies on safety, efficacy, and tolerability of long-term isavuconazole use are needed.
Published: 2022

16. IRS Penalty Report: A Call for Objective Standards

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

17. Filling the Ethical Void: Treasury's 1986 Circular 230 Proposal

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

18. Tax Politics and the New Substantial Understatement Penalty

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

19. Lowering the Bar: ABA Formal Opinion 85-352

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

20. No Joke: Circular 230 is Here to Stay

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

21. Vices and Virtues of an Objective Reporting Standard

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

22. Reasonable Basis and Ethical Standards Before 1980

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

23. ABA Formal Opinion 346 and a New Statutory Penalty Regime

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

24. Raising the Ethical Bar for Tax Lawyers: Why We Need Circular 230

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

25. The Reaction to the 1980 Proposed Amendments to Circular 230

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

26. Tax Shelter Opinions Threatened the Tax System in the 1970s

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

27. Straight Talk About the 'Death' Tax: Politics, Economics, and Morality

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

28. No Income Splitting for Domestic Partners: How the IRS Erred

Author: Ventry, Dennis J, Ventry, Dennis J, Ventry, Dennis J, and Ventry, Dennis J
Published: 2022

29. The Cerebellum and Disorders of Emotion

Author: Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Schutter, Dennis J L G, Adamaszek, Michael, Manto, Mario, Schutter, Dennis J. L. G., Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Schutter, Dennis J L G, Adamaszek, Michael, Manto, Mario, and Schutter, Dennis J. L. G.
Published: 2022

30. Introduction into the Role of the Cerebellum in Emotion

Author: Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Adamaszek, Michael, Manto, Mario, Schutter, Dennis J L G, Schutter, Dennis J. L. G, Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Adamaszek, Michael, Manto, Mario, Schutter, Dennis J L G, and Schutter, Dennis J. L. G
Published: 2022

31. Current and Future Perspectives of the Cerebellum in Affective Neuroscience

Author: Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Adamaszek, Michael, Manto, Mario, Schutter, Dennis J L G, Schutter, Dennis J. L. G, Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Adamaszek, Michael, Manto, Mario, Schutter, Dennis J L G, and Schutter, Dennis J. L. G
Published: 2022

32. Pharmacokinetics of isavuconazole in healthy cats after oral and intravenous administration.

Author: Woerde, Dennis J, Woerde, Dennis J, Wittenburg, Luke A, Dear, Jonathan D, Woerde, Dennis J, Woerde, Dennis J, Wittenburg, Luke A, and Dear, Jonathan D
Abstract: BackgroundIsavuconazole is a triazole antifungal drug that has shown good efficacy in human patients. Absorption and pharmacokinetics have not been evaluated in cats.ObjectivesTo determine the pharmacokinetics of isavuconazole in cats given a single IV or PO dose.AnimalsEight healthy, adult research cats.MethodsFour cats received 100 mg capsules of isavuconazole PO. Four cats received 5 mg/kg isavuconazole solution IV. Serum was collected at predetermined intervals for analysis using ultra-high performance liquid chromatography-tandem mass spectrometry. Data were analyzed using a 2-compartment uniform weighting pharmacokinetic analysis with lag time for PO administration and a 2 compartment, 1/y2 weighting for IV administration. Predicted 24 and 48-hour dosing intervals of 100 mg isavuconazole administered PO were modeled and in vitro plasma protein binding was assessed.ResultsBoth PO and IV drug administration resulted in high serum concentrations. Intravenous and PO formulations of isavuconazole appear to be able to be used interchangeably. Peak serum isavuconazole concentrations occurred 5 ± 3.8 hours after PO administration with an elimination rate half-life of 66.2 ± 55.3 hours. Intersubject variability was apparent in both the PO and IV groups. Two cats vomited 6 to 8 hours after PO administration. No adverse effects were observed in the IV group. Oral bioavailability was estimated to be approximately 88%. Serum protein binding was calculated to be approximately 99.0% ± 0.03%.Conclusions and clinical importanceIsavuconazole might prove to be useful in cats with fungal disease given its favorable pharmacokinetics. Additional studies on safety, efficacy, and tolerability of long-term isavuconazole use are needed.
Published: 2022

33. Non-invasive Brain Stimulation of the Cerebellum in Emotion

Author: Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Adamaszek, Michael, Manto, Mario, Schutter, Dennis J. L. G., Klaus, Jana, Schutter, Dennis J L G, Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Adamaszek, Michael, Manto, Mario, Schutter, Dennis J. L. G., Klaus, Jana, and Schutter, Dennis J L G
Published: 2022

34. The Cerebellum and Disorders of Emotion

Author: Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Adamaszek, Michael, Manto, Mario, Schutter, Dennis J. L. G., Schutter, Dennis J L G, Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Adamaszek, Michael, Manto, Mario, Schutter, Dennis J. L. G., and Schutter, Dennis J L G
Published: 2022

35. Introduction into the Role of the Cerebellum in Emotion

Author: Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Adamaszek, Michael, Manto, Mario, Schutter, Dennis J. L. G, Schutter, Dennis J L G, Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Adamaszek, Michael, Manto, Mario, Schutter, Dennis J. L. G, and Schutter, Dennis J L G
Published: 2022

36. Current and Future Perspectives of the Cerebellum in Affective Neuroscience

Author: Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Adamaszek, Michael, Manto, Mario, Schutter, Dennis J. L. G, Schutter, Dennis J L G, Leerstoel Schutter, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Adamaszek, Michael, Manto, Mario, Schutter, Dennis J. L. G, and Schutter, Dennis J L G
Published: 2022

37. Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases

Author: Figlioli, G, Billaud, A, Wang, Q, Bolla, MK, Dennis, J, Lush, M, Kvist, A, Adank, MA, Ahearn, TU, Antonenkova, NN, Auvinen, P, Behrens, S, Bermisheva, M, Bogdanova, N, Bojesen, SE, Bonanni, B, Bruening, T, Camp, NJ, Campbell, A, Castelao, JE, Cessna, MH, Czene, K, Devilee, P, Doerk, T, Eriksson, M, Fasching, PA, Flyger, H, Gabrielson, M, Gago-Dominguez, M, Garcia-Closas, M, Glendon, G, Garcia, EG, Gonzalez-Neira, A, Grassmann, F, Guenel, P, Hahnen, E, Hamann, U, Hillemanns, P, Hooning, MJ, Hoppe, R, Howell, A, Humphreys, K, Jakubowska, A, Khusnutdinova, EK, Kristensen, VN, Lindblom, A, Loizidou, MA, Lubinski, J, Mannermaa, A, Maurer, T, Mavroudis, D, Newman, WG, Obi, N, Panayiotidis, M, Radice, P, Rashid, MU, Rhenius, V, Ruebner, M, Saloustros, E, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Shah, MT, Southey, MC, Tomlinson, I, Truong, T, van Veen, EM, Wendt, C, Yang, XR, Michailidou, K, Dunning, AM, Pharoah, PDP, Easton, DF, Andrulis, IL, Evans, DG, Hollestelle, A, Chang-Claude, J, Milne, RL, Peterlongo, P, Figlioli, G, Billaud, A, Wang, Q, Bolla, MK, Dennis, J, Lush, M, Kvist, A, Adank, MA, Ahearn, TU, Antonenkova, NN, Auvinen, P, Behrens, S, Bermisheva, M, Bogdanova, N, Bojesen, SE, Bonanni, B, Bruening, T, Camp, NJ, Campbell, A, Castelao, JE, Cessna, MH, Czene, K, Devilee, P, Doerk, T, Eriksson, M, Fasching, PA, Flyger, H, Gabrielson, M, Gago-Dominguez, M, Garcia-Closas, M, Glendon, G, Garcia, EG, Gonzalez-Neira, A, Grassmann, F, Guenel, P, Hahnen, E, Hamann, U, Hillemanns, P, Hooning, MJ, Hoppe, R, Howell, A, Humphreys, K, Jakubowska, A, Khusnutdinova, EK, Kristensen, VN, Lindblom, A, Loizidou, MA, Lubinski, J, Mannermaa, A, Maurer, T, Mavroudis, D, Newman, WG, Obi, N, Panayiotidis, M, Radice, P, Rashid, MU, Rhenius, V, Ruebner, M, Saloustros, E, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Shah, MT, Southey, MC, Tomlinson, I, Truong, T, van Veen, EM, Wendt, C, Yang, XR, Michailidou, K, Dunning, AM, Pharoah, PDP, Easton, DF, Andrulis, IL, Evans, DG, Hollestelle, A, Chang-Claude, J, Milne, RL, and Peterlongo, P
Abstract: FANCM germline protein truncating variants (PTVs) are moderate-risk factors for ER-negative breast cancer. We previously described the spectrum of FANCM PTVs in 114 European breast cancer cases. In the present, larger cohort, we report the spectrum and frequency of four common and 62 rare FANCM PTVs found in 274 carriers detected among 44,803 breast cancer cases. We confirmed that p.Gln1701* was the most common PTV in Northern Europe with lower frequencies in Southern Europe. In contrast, p.Gly1906Alafs*12 was the most common PTV in Southern Europe with decreasing frequencies in Central and Northern Europe. We verified that p.Arg658* was prevalent in Central Europe and had highest frequencies in Eastern Europe. We also confirmed that the fourth most common PTV, p.Gln498Thrfs*7, might be a founder variant from Lithuania. Based on the frequency distribution of the carriers of rare PTVs, we showed that the FANCM PTVs spectra in Southwestern and Central Europe were much more heterogeneous than those from Northeastern Europe. These findings will inform the development of more efficient FANCM genetic testing strategies for breast cancer cases from specific European populations.
Published: 2023

38. Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel

Author: Levi, H, Carmi, S, Rosset, S, Yerushalmi, R, Zick, A, Yablonski-Peretz, T, Wang, Q, Bolla, MK, Dennis, J, Michailidou, K, Lush, M, Ahearn, T, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Arndt, V, Augustinsson, A, Auvinen, P, Freeman, LB, Beckmann, M, Behrens, S, Bermisheva, M, Bodelon, C, Bogdanova, NV, Bojesen, SE, Brenner, H, Byers, H, Camp, N, Castelao, J, Chang-Claude, J, Chirlaque, M-D, Chung, W, Clarke, C, Collee, MJ, Colonna, S, Couch, F, Cox, A, Cross, SS, Czene, K, Daly, M, Devilee, P, Dork, T, Dossus, L, Eccles, DM, Eliassen, AH, Eriksson, M, Evans, G, Fasching, P, Fletcher, O, Flyger, H, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Garcia-Closas, M, Garcia-Saenz, JA, Genkinger, J, Giles, GG, Goldberg, M, Guenel, P, Hall, P, Hamann, U, He, W, Hillemanns, P, Hollestelle, A, Hoppe, R, Hopper, J, Jakovchevska, S, Jakubowska, A, Jernstrom, H, John, E, Johnson, N, Jones, M, Vijai, J, Kaaks, R, Khusnutdinova, E, Kitahara, C, Koutros, S, Kristensen, V, Kurian, AW, Lacey, J, Lambrechts, D, Le Marchand, L, Lejbkowicz, F, Lindblom, A, Loibl, S, Lori, A, Lubinski, J, Mannermaa, A, Manoochehri, M, Mavroudis, D, Menon, U, Mulligan, A, Murphy, R, Nevelsteen, I, Newman, WG, Obi, N, O'Brien, K, Offit, K, Olshan, A, Plaseska-Karanfilska, D, Olson, J, Panico, S, Park-Simon, T-W, Patel, A, Peterlongo, P, Rack, B, Radice, P, Rennert, G, Rhenius, V, Romero, A, Saloustros, E, Sandler, D, Schmidt, MK, Schwentner, L, Shah, M, Sharma, P, Simard, J, Southey, M, Stone, J, Tapper, WJ, Taylor, J, Teras, L, Toland, AE, Troester, M, Truong, T, van der Kolk, LE, Weinberg, C, Wendt, C, Yang, XR, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, P, Easton, DF, Ben-Sachar, S, Elefant, N, Shamir, R, Elkon, R, Levi, H, Carmi, S, Rosset, S, Yerushalmi, R, Zick, A, Yablonski-Peretz, T, Wang, Q, Bolla, MK, Dennis, J, Michailidou, K, Lush, M, Ahearn, T, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Arndt, V, Augustinsson, A, Auvinen, P, Freeman, LB, Beckmann, M, Behrens, S, Bermisheva, M, Bodelon, C, Bogdanova, NV, Bojesen, SE, Brenner, H, Byers, H, Camp, N, Castelao, J, Chang-Claude, J, Chirlaque, M-D, Chung, W, Clarke, C, Collee, MJ, Colonna, S, Couch, F, Cox, A, Cross, SS, Czene, K, Daly, M, Devilee, P, Dork, T, Dossus, L, Eccles, DM, Eliassen, AH, Eriksson, M, Evans, G, Fasching, P, Fletcher, O, Flyger, H, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Garcia-Closas, M, Garcia-Saenz, JA, Genkinger, J, Giles, GG, Goldberg, M, Guenel, P, Hall, P, Hamann, U, He, W, Hillemanns, P, Hollestelle, A, Hoppe, R, Hopper, J, Jakovchevska, S, Jakubowska, A, Jernstrom, H, John, E, Johnson, N, Jones, M, Vijai, J, Kaaks, R, Khusnutdinova, E, Kitahara, C, Koutros, S, Kristensen, V, Kurian, AW, Lacey, J, Lambrechts, D, Le Marchand, L, Lejbkowicz, F, Lindblom, A, Loibl, S, Lori, A, Lubinski, J, Mannermaa, A, Manoochehri, M, Mavroudis, D, Menon, U, Mulligan, A, Murphy, R, Nevelsteen, I, Newman, WG, Obi, N, O'Brien, K, Offit, K, Olshan, A, Plaseska-Karanfilska, D, Olson, J, Panico, S, Park-Simon, T-W, Patel, A, Peterlongo, P, Rack, B, Radice, P, Rennert, G, Rhenius, V, Romero, A, Saloustros, E, Sandler, D, Schmidt, MK, Schwentner, L, Shah, M, Sharma, P, Simard, J, Southey, M, Stone, J, Tapper, WJ, Taylor, J, Teras, L, Toland, AE, Troester, M, Truong, T, van der Kolk, LE, Weinberg, C, Wendt, C, Yang, XR, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, P, Easton, DF, Ben-Sachar, S, Elefant, N, Shamir, R, and Elkon, R
Abstract: BACKGROUND: Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women. METHODS: We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel. RESULTS: In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28). CONCLUSIONS: Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.
Published: 2023

39. A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants: Application to BRCA1 and BRCA2

Author: Cutting, G, Zanti, M, O'Mahony, DG, Parsons, MT, Li, H, Dennis, J, Aittomakkiki, K, Andrulis, IL, Anton-Culver, H, Aronson, KJ, Augustinsson, A, Becher, H, Bojesen, SE, Bolla, MK, Brenner, H, Brown, MA, Buys, SS, Canzian, F, Caputo, SM, Castelao, JE, Chang-Claude, J, Czene, K, Daly, MB, De Nicolo, A, Devilee, P, Dork, T, Dunning, AM, Dwek, M, Eccles, DM, Engel, C, Evans, DG, Fasching, PA, Gago-Dominguez, M, Garcia-Closas, M, Garcia-Saenz, JA, Gentry-Maharaj, A, Geurts-Giele, WRR, Giles, GG, Glendon, G, Goldberg, MS, Garcia, EBG, Guendert, M, Guenel, P, Hahnen, E, Haiman, CA, Hall, P, Hamann, U, Harkness, EF, Hogervorst, FBL, Hollestelle, A, Hoppe, R, Hopper, JL, Houdayer, C, Houlston, RS, Howell, A, Investigators, A, Jakimovska, M, Jakubowska, A, Jernstrom, H, John, EM, Kaaks, R, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Lacey, J, Lambrechts, D, Leone, M, Lindblom, A, Lush, M, Mannermaa, A, Manoochehri, M, Manoukian, S, Margolin, S, Martinez, ME, Menon, U, Milne, RL, Monteiro, AN, Murphy, RA, Neuhausen, SL, Nevanlinna, H, Newman, WG, Offit, K, Park, SK, James, P, Peterlongo, P, Peto, J, Plaseska-Karanfilska, D, Punie, K, Radice, P, Rashid, MU, Rennert, G, Romero, A, Rosenberg, EH, Saloustros, E, Sandler, DP, Schmidt, MK, Schmutzler, RK, Shu, X-O, Simard, J, Southey, MC, Stone, J, Stoppa-Lyonnet, D, Tamimi, RM, Tapper, WJ, Taylor, JA, Teo, SH, Teras, LR, Terry, MB, Thomassen, M, Troester, MA, Vachon, CM, Vega, A, Vreeswijk, MPG, Wang, Q, Wappenschmidt, B, Weinberg, CR, Wolk, A, Zheng, W, Feng, B, Couch, FJ, Spurdle, AB, Easton, DF, Goldgar, DE, Michailidou, K, Cutting, G, Zanti, M, O'Mahony, DG, Parsons, MT, Li, H, Dennis, J, Aittomakkiki, K, Andrulis, IL, Anton-Culver, H, Aronson, KJ, Augustinsson, A, Becher, H, Bojesen, SE, Bolla, MK, Brenner, H, Brown, MA, Buys, SS, Canzian, F, Caputo, SM, Castelao, JE, Chang-Claude, J, Czene, K, Daly, MB, De Nicolo, A, Devilee, P, Dork, T, Dunning, AM, Dwek, M, Eccles, DM, Engel, C, Evans, DG, Fasching, PA, Gago-Dominguez, M, Garcia-Closas, M, Garcia-Saenz, JA, Gentry-Maharaj, A, Geurts-Giele, WRR, Giles, GG, Glendon, G, Goldberg, MS, Garcia, EBG, Guendert, M, Guenel, P, Hahnen, E, Haiman, CA, Hall, P, Hamann, U, Harkness, EF, Hogervorst, FBL, Hollestelle, A, Hoppe, R, Hopper, JL, Houdayer, C, Houlston, RS, Howell, A, Investigators, A, Jakimovska, M, Jakubowska, A, Jernstrom, H, John, EM, Kaaks, R, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Lacey, J, Lambrechts, D, Leone, M, Lindblom, A, Lush, M, Mannermaa, A, Manoochehri, M, Manoukian, S, Margolin, S, Martinez, ME, Menon, U, Milne, RL, Monteiro, AN, Murphy, RA, Neuhausen, SL, Nevanlinna, H, Newman, WG, Offit, K, Park, SK, James, P, Peterlongo, P, Peto, J, Plaseska-Karanfilska, D, Punie, K, Radice, P, Rashid, MU, Rennert, G, Romero, A, Rosenberg, EH, Saloustros, E, Sandler, DP, Schmidt, MK, Schmutzler, RK, Shu, X-O, Simard, J, Southey, MC, Stone, J, Stoppa-Lyonnet, D, Tamimi, RM, Tapper, WJ, Taylor, JA, Teo, SH, Teras, LR, Terry, MB, Thomassen, M, Troester, MA, Vachon, CM, Vega, A, Vreeswijk, MPG, Wang, Q, Wappenschmidt, B, Weinberg, CR, Wolk, A, Zheng, W, Feng, B, Couch, FJ, Spurdle, AB, Easton, DF, Goldgar, DE, and Michailidou, K
Abstract: A large number of variants identified through clinical genetic testing in disease susceptibility genes, are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion), can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analyses of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC), and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity - findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared to classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and pre-formatted excel calculators for implementation of the method for rare variants in BRCA1, BRCA2 and other high-risk genes with known penetrance.
Published: 2023

40. The human cerebellum in reward anticipation and outcome processing: An activation likelihood estimation meta-analysis

Author: Kruithof, Eline S, Klaus, Jana, Schutter, Dennis J L G, Kruithof, Eline S, Klaus, Jana, and Schutter, Dennis J L G
Abstract: The cerebellum generates internal prediction models and actively compares anticipated and actual outcomes in order to reach a desired end state. In this process, reward can serve as a reinforcer that shapes internal prediction models, enabling context-appropriate behavior. While the involvement of the cerebellum in reward processing has been established in animals, there is no detailed account of which cerebellar regions are involved in reward anticipation and outcome processing in humans. To this end, an activation likelihood estimation meta-analysis of functional neuroimaging studies was performed to investigate cerebellar functional activity patterns associated with reward anticipation and outcome processing in healthy adults. Results showed that reward anticipation (k = 31) was associated with regional activity in the bilateral anterior lobe, bilateral lobule VI, left Crus I and the posterior vermis, while reward outcome (k = 16) was associated with regional activity in the declive and left lobule VI. These findings demonstrate distinct involvement of the cerebellum in reward anticipation and outcome processing as part of a predictive coding routine.
Published: 2023

41. A Comparative Perspective on the Cerebello-Cerebral System and Its Link to Cognition

Author: Magielse, Neville, Heuer, Katja, Toro, Roberto, Schutter, Dennis J L G, Valk, Sofie L, Magielse, Neville, Heuer, Katja, Toro, Roberto, Schutter, Dennis J L G, and Valk, Sofie L
Abstract: The longstanding idea that the cerebral cortex is the main neural correlate of human cognition can be elaborated by comparative analyses along the vertebrate phylogenetic tree that support the view that the cerebello-cerebral system is suited to support non-motor functions more generally. In humans, diverse accounts have illustrated cerebellar involvement in cognitive functions. Although the neocortex, and its transmodal association cortices such as the prefrontal cortex, have become disproportionately large over primate evolution specifically, human neocortical volume does not appear to be exceptional relative to the variability within primates. Rather, several lines of evidence indicate that the exceptional volumetric increase of the lateral cerebellum in conjunction with its connectivity with the cerebral cortical system may be linked to non-motor functions and mental operation in primates. This idea is supported by diverging cerebello-cerebral adaptations that potentially coevolve with cognitive abilities across other vertebrates such as dolphins, parrots, and elephants. Modular adaptations upon the vertebrate cerebello-cerebral system may thus help better understand the neuroevolutionary trajectory of the primate brain and its relation to cognition in humans. Lateral cerebellar lobules crura I-II and their reciprocal connections to the cerebral cortical association areas appear to have substantially expanded in great apes, and humans. This, along with the notable increase in the ventral portions of the dentate nucleus and a shift to increased relative prefrontal-cerebellar connectivity, suggests that modular cerebellar adaptations support cognitive functions in humans. In sum, we show how comparative neuroscience provides new avenues to broaden our understanding of cerebellar and cerebello-cerebral functions in the context of cognition.
Published: 2023

42. Correction: Cerebellar Grey Matter Volumes in Reactive Aggression and Impulsivity in Healthy Volunteers

Author: Wolfs, Elze M L, Klaus, Jana, Schutter, Dennis J L G, Wolfs, Elze M L, Klaus, Jana, and Schutter, Dennis J L G
Abstract: The original version of this article unfortunately contained an error. In the Methods section in the original version of the article, “five-point scale" should read “seven-point scale”.This typographical mistake has been amended in the corrected version of the article.
Published: 2023

43. Effects of Multisession Transcranial Direct Current Stimulation on Stress Regulation and Emotional Working Memory: A Randomized Controlled Trial in Healthy Military Personnel

Author: Smits, Fenne M, Geuze, Elbert, de Kort, Guido J, Kouwer, Karlijn, Geerlings, Lisa, van Honk, Jack, Schutter, Dennis J L G, Smits, Fenne M, Geuze, Elbert, de Kort, Guido J, Kouwer, Karlijn, Geerlings, Lisa, van Honk, Jack, and Schutter, Dennis J L G
Abstract: Objectives: Top-down stress regulation, important for military operational performance and mental health, involves emotional working memory and the dorsolateral prefrontal cortex (DLPFC). Multisession transcranial direct current stimulation (tDCS) applied over the DLPFC during working memory training has been shown to improve working memory performance. This study tested the hypothesis that combined tDCS with working memory training also improves top-down stress regulation. However, tDCS response differs between individuals. Resting-state electrophysiological brain activity was post hoc explored as a possible predictor of tDCS response. The predictive value of the ratio between slow-wave theta oscillations and fast-wave beta oscillations (theta/beta ratio) was examined, together with the previously identified tDCS response predictors age, education, and baseline working memory performance. Materials and Methods: Healthy military service members (n = 79) underwent three sessions of real or sham tDCS over the right DLPFC (anode: F4, cathode: behind C2) at 2 mA for 20 minutes during emotional working memory training (N-back task). At baseline and within a week after the tDCS training sessions, stress regulation was assessed by fear-potentiated startle responses and subjective fear in a threat-of-shock paradigm with instructed emotional downregulation. Results were analyzed in generalized linear mixed-effects models. Results: Threat-of-shock responses and emotional working memory performance showed no significant group-level effects of the real vs sham tDCS training intervention (p > 0.07). In contrast, when considering baseline theta/beta ratios or the other tDCS response predictors, exploratory results showed a trait-dependent beneficial effect of tDCS on emotional working memory training performance during the first session (p < 0.01). Conclusions: No evidence was found for effectivity of the tDCS training intervention to improve stress regulation in healthy
Published: 2023

44. Cerebellar Grey Matter Volumes in Reactive Aggression and Impulsivity in Healthy Volunteers

Author: Wolfs, Elze M. L., Klaus, Jana, Schutter, Dennis J. L. G., Wolfs, Elze M. L., Klaus, Jana, and Schutter, Dennis J. L. G.
Abstract: Several lines of evidence point towards the involvement of the cerebellum in reactive aggression. In addition to the posterior cerebellar hemisphere, the vermis has been suggested to play a prominent role in impulse regulation. In the present study, we set out to further examine the relationships between cerebellar grey matter volumes, aggression, and impulsivity in 201 healthy volunteers. 3 T structural magnetic resonance imaging scans were acquired to investigate grey matter volumes of the cerebellar vermis and the anterior and posterior lobules. Aggression was assessed with the Buss–Perry Aggression Questionnaire and impulsivity was measured with the Barratt Impulsiveness Scale-11. Results showed that impulsivity was positively associated with grey matter volumes of the cerebellar vermis and inversely correlated with grey matter volumes of the right posterior lobule. In addition, smaller volumes of the right posterior lobules were associated with higher physical aggression. Exploratory analyses indicated that for the right hemisphere, this association was driven by grey matter volumes of lobules VIIb and VIIIa. Our findings provide correlational evidence in healthy volunteers for the involvement of the cerebellar vermis and posterior lobules in a cortico-limbic-cerebellar circuit of aggression.
Published: 2023

45. Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer

Author: Wichert, K, Hoppe, R, Ickstadt, K, Behrens, T, Winter, S, Herold, R, Terschueren, C, Lo, W-Y, Guenel, P, Truong, T, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Lush, M, Andrulis, IL, Brenner, H, Chang-Claude, J, Cox, A, Cross, SS, Czene, K, Eriksson, M, Figueroa, JD, Garcia-Closas, M, Goldberg, MS, Hamann, U, He, W, Holleczek, B, Hopper, JL, Jakubowska, A, Ko, Y-D, Lubinski, J, Mulligan, AM, Obi, N, Rhenius, V, Shah, M, Shu, X-O, Simard, J, Southey, MC, Zheng, W, Dunning, AM, Pharoah, PDP, Hall, P, Easton, DF, Bruening, T, Brauch, H, Harth, V, Rabstein, S, Wichert, K, Hoppe, R, Ickstadt, K, Behrens, T, Winter, S, Herold, R, Terschueren, C, Lo, W-Y, Guenel, P, Truong, T, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Lush, M, Andrulis, IL, Brenner, H, Chang-Claude, J, Cox, A, Cross, SS, Czene, K, Eriksson, M, Figueroa, JD, Garcia-Closas, M, Goldberg, MS, Hamann, U, He, W, Holleczek, B, Hopper, JL, Jakubowska, A, Ko, Y-D, Lubinski, J, Mulligan, AM, Obi, N, Rhenius, V, Shah, M, Shu, X-O, Simard, J, Southey, MC, Zheng, W, Dunning, AM, Pharoah, PDP, Hall, P, Easton, DF, Bruening, T, Brauch, H, Harth, V, and Rabstein, S
Abstract: Light-at-night triggers the decline of pineal gland melatonin biosynthesis and secretion and is an IARC-classified probable breast-cancer risk factor. We applied a large-scale molecular epidemiology approach to shed light on the putative role of melatonin in breast cancer. We investigated associations between breast-cancer risk and polymorphisms at genes of melatonin biosynthesis/signaling using a study population of 44,405 women from the Breast Cancer Association Consortium (22,992 cases, 21,413 population-based controls). Genotype data of 97 candidate single nucleotide polymorphisms (SNPs) at 18 defined gene regions were investigated for breast-cancer risk effects. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CI) by logistic regression for the main-effect analysis as well as stratified analyses by estrogen- and progesterone-receptor (ER, PR) status. SNP-SNP interactions were analyzed via a two-step procedure based on logic regression. The Bayesian false-discovery probability (BFDP) was used for all analyses to account for multiple testing. Noteworthy associations (BFDP < 0.8) included 10 linked SNPs in tryptophan hydroxylase 2 (TPH2) (e.g. rs1386492: OR = 1.07, 95% CI 1.02-1.12), and a SNP in the mitogen-activated protein kinase 8 (MAPK8) (rs10857561: OR = 1.11, 95% CI 1.04-1.18). The SNP-SNP interaction analysis revealed noteworthy interaction terms with TPH2- and MAPK-related SNPs (e.g. rs1386483R ∧ rs1473473D ∧ rs3729931D: OR = 1.20, 95% CI 1.09-1.32). In line with the light-at-night hypothesis that links shift work with elevated breast-cancer risks our results point to SNPs in TPH2 and MAPK-genes that may impact the intricate network of circadian regulation.
Published: 2023

46. Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Author: Mueller, SH, Lai, AG, Valkovskaya, M, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Lush, M, Abu-Ful, Z, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Baert, T, Freeman, LEB, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Blomqvist, C, Bogdanova, N, Bojesen, SE, Bonanni, B, Brenner, H, Brucker, SY, Buys, SS, Castelao, JE, Chan, TL, Chang-Claude, J, Chanock, SJ, Choi, J-Y, Chung, WK, Colonna, S, Cornelissen, S, Couch, FJ, Czene, K, Daly, MB, Devilee, P, Dork, T, Dossus, L, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Engel, C, Evans, DG, Fasching, PA, Fletcher, O, Flyger, H, Gago-Dominguez, M, Gao, Y-T, Garcia-Closas, M, Garcia-Saenz, JA, Genkinger, J, Gentry-Maharaj, A, Grassmann, F, Guenel, P, Gundert, M, Haeberle, L, Hahnen, E, Haiman, CA, Hakansson, N, Hall, P, Harkness, EF, Harrington, PA, Hartikainen, JM, Hartman, M, Hein, A, Ho, W-K, Hooning, MJ, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Hunter, DJ, Huo, D, Investigators, A, Ito, H, Iwasaki, M, Jakubowska, A, Janni, W, John, EM, Jones, ME, Jung, A, Kaaks, R, Kang, D, Khusnutdinova, EK, Kim, S-W, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Kubelka-Sabit, K, Kurian, AW, Kwong, A, Lacey, J, Lambrechts, D, Le Marchand, L, Li, J, Linet, M, Lo, W-Y, Long, J, Lophatananon, A, Mannermaa, A, Manoochehri, M, Margolin, S, Matsuo, K, Mavroudis, D, Menon, U, Muir, K, Murphy, RA, Nevanlinna, H, Newman, WG, Niederacher, D, O'Brien, KM, Obi, N, Offit, K, Olopade, O, Olshan, AF, Olsson, H, Park, SK, Patel, A, Perou, CM, Peto, J, Pharoah, PDP, Plaseska-Karanfilska, D, Presneau, N, Rack, B, Radice, P, Ramachandran, D, Rashid, MU, Rennert, G, Romero, A, Ruddy, KJ, Ruebner, M, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Schneider, MO, Scott, C, Shah, M, Sharma, P, Shen, C-Y, Shu, X-O, Simard, J, Surowy, H, Tamimi, RM, Tapper, WJ, Taylor, JA, Teo, SH, Teras, LR, Toland, AE, Tollenaar, RAEM, Torres, D, Torres-Mejia, G, Troester, MA, Truong, T, Vachon, CM, Vijai, J, Weinberg, CR, Wendt, C, Winqvist, R, Wolk, A, Wu, AH, Yamaji, T, Yang, XR, Yu, J-C, Zheng, W, Ziogas, A, Ziv, E, Dunning, AM, Easton, DF, Hemingway, H, Hamann, U, Kuchenbaecker, KB, Mueller, SH, Lai, AG, Valkovskaya, M, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Lush, M, Abu-Ful, Z, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arndt, V, Aronson, KJ, Augustinsson, A, Baert, T, Freeman, LEB, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Blomqvist, C, Bogdanova, N, Bojesen, SE, Bonanni, B, Brenner, H, Brucker, SY, Buys, SS, Castelao, JE, Chan, TL, Chang-Claude, J, Chanock, SJ, Choi, J-Y, Chung, WK, Colonna, S, Cornelissen, S, Couch, FJ, Czene, K, Daly, MB, Devilee, P, Dork, T, Dossus, L, Dwek, M, Eccles, DM, Ekici, AB, Eliassen, AH, Engel, C, Evans, DG, Fasching, PA, Fletcher, O, Flyger, H, Gago-Dominguez, M, Gao, Y-T, Garcia-Closas, M, Garcia-Saenz, JA, Genkinger, J, Gentry-Maharaj, A, Grassmann, F, Guenel, P, Gundert, M, Haeberle, L, Hahnen, E, Haiman, CA, Hakansson, N, Hall, P, Harkness, EF, Harrington, PA, Hartikainen, JM, Hartman, M, Hein, A, Ho, W-K, Hooning, MJ, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Hunter, DJ, Huo, D, Investigators, A, Ito, H, Iwasaki, M, Jakubowska, A, Janni, W, John, EM, Jones, ME, Jung, A, Kaaks, R, Kang, D, Khusnutdinova, EK, Kim, S-W, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Kubelka-Sabit, K, Kurian, AW, Kwong, A, Lacey, J, Lambrechts, D, Le Marchand, L, Li, J, Linet, M, Lo, W-Y, Long, J, Lophatananon, A, Mannermaa, A, Manoochehri, M, Margolin, S, Matsuo, K, Mavroudis, D, Menon, U, Muir, K, Murphy, RA, Nevanlinna, H, Newman, WG, Niederacher, D, O'Brien, KM, Obi, N, Offit, K, Olopade, O, Olshan, AF, Olsson, H, Park, SK, Patel, A, Perou, CM, Peto, J, Pharoah, PDP, Plaseska-Karanfilska, D, Presneau, N, Rack, B, Radice, P, Ramachandran, D, Rashid, MU, Rennert, G, Romero, A, Ruddy, KJ, Ruebner, M, Saloustros, E, Sandler, DP, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Schneider, MO, Scott, C, Shah, M, Sharma, P, Shen, C-Y, Shu, X-O, Simard, J, Surowy, H, Tamimi, RM, Tapper, WJ, Taylor, JA, Teo, SH, Teras, LR, Toland, AE, Tollenaar, RAEM, Torres, D, Torres-Mejia, G, Troester, MA, Truong, T, Vachon, CM, Vijai, J, Weinberg, CR, Wendt, C, Winqvist, R, Wolk, A, Wu, AH, Yamaji, T, Yang, XR, Yu, J-C, Zheng, W, Ziogas, A, Ziv, E, Dunning, AM, Easton, DF, Hemingway, H, Hamann, U, and Kuchenbaecker, KB
Abstract: BACKGROUND: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. METHODS: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. RESULTS: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10-6) and AC058822.1 (P = 1.47 × 10-4), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. CONCLUSIONS: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10-5), demonstrating the importance of diversifying study cohorts.
Published: 2023

47. Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival.

Author: Morra, A, Schreurs, MAC, Andrulis, IL, Anton-Culver, H, Augustinsson, A, Beckmann, MW, Behrens, S, Bojesen, SE, Bolla, MK, Brauch, H, Broeks, A, Buys, SS, Camp, NJ, Castelao, JE, Cessna, MH, Chang-Claude, J, Chung, WK, Collaborators, N, Colonna, SV, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Dennis, J, Devilee, P, Dörk, T, Dunning, AM, Dwek, M, Easton, DF, Eccles, DM, Eriksson, M, Evans, DG, Fasching, PA, Fehm, TN, Figueroa, JD, Flyger, H, Gabrielson, M, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, Genkinger, J, Grassmann, F, Gündert, M, Hahnen, E, Haiman, CA, Hamann, U, Harrington, PA, Hartikainen, JM, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Investigators, A, Investigators, K, Jakubowska, A, Janni, W, Jernström, H, John, EM, Johnson, N, Jones, ME, Kristensen, VN, Kurian, AW, Lambrechts, D, Marchand, LL, Lindblom, A, Lubiński, J, Lux, MP, Mannermaa, A, Mavroudis, D, Mulligan, AM, Muranen, TA, Nevanlinna, H, Nevelsteen, I, Neven, P, Newman, WG, Obi, N, Offit, K, Olshan, AF, Park-Simon, T-W, Patel, AV, Peterlongo, P, Phillips, K-A, Plaseska-Karanfilska, D, Polley, EC, Presneau, N, Pylkäs, K, Rack, B, Radice, P, Rashid, MU, Rhenius, V, Robson, M, Romero, A, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schuetze, S, Scott, C, Shah, M, Smichkoska, S, Southey, MC, Tapper, WJ, Teras, LR, Tollenaar, RAEM, Tomczyk, K, Tomlinson, I, Troester, MA, Vachon, CM, van Veen, EM, Wang, Q, Wendt, C, Wildiers, H, Winqvist, R, Ziogas, A, Hall, P, Pharoah, PDP, Adank, MA, Hollestelle, A, Schmidt, MK, Hooning, MJ, Morra, A, Schreurs, MAC, Andrulis, IL, Anton-Culver, H, Augustinsson, A, Beckmann, MW, Behrens, S, Bojesen, SE, Bolla, MK, Brauch, H, Broeks, A, Buys, SS, Camp, NJ, Castelao, JE, Cessna, MH, Chang-Claude, J, Chung, WK, Collaborators, N, Colonna, SV, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Dennis, J, Devilee, P, Dörk, T, Dunning, AM, Dwek, M, Easton, DF, Eccles, DM, Eriksson, M, Evans, DG, Fasching, PA, Fehm, TN, Figueroa, JD, Flyger, H, Gabrielson, M, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, Genkinger, J, Grassmann, F, Gündert, M, Hahnen, E, Haiman, CA, Hamann, U, Harrington, PA, Hartikainen, JM, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Investigators, A, Investigators, K, Jakubowska, A, Janni, W, Jernström, H, John, EM, Johnson, N, Jones, ME, Kristensen, VN, Kurian, AW, Lambrechts, D, Marchand, LL, Lindblom, A, Lubiński, J, Lux, MP, Mannermaa, A, Mavroudis, D, Mulligan, AM, Muranen, TA, Nevanlinna, H, Nevelsteen, I, Neven, P, Newman, WG, Obi, N, Offit, K, Olshan, AF, Park-Simon, T-W, Patel, AV, Peterlongo, P, Phillips, K-A, Plaseska-Karanfilska, D, Polley, EC, Presneau, N, Pylkäs, K, Rack, B, Radice, P, Rashid, MU, Rhenius, V, Robson, M, Romero, A, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schuetze, S, Scott, C, Shah, M, Smichkoska, S, Southey, MC, Tapper, WJ, Teras, LR, Tollenaar, RAEM, Tomczyk, K, Tomlinson, I, Troester, MA, Vachon, CM, van Veen, EM, Wang, Q, Wendt, C, Wildiers, H, Winqvist, R, Ziogas, A, Hall, P, Pharoah, PDP, Adank, MA, Hollestelle, A, Schmidt, MK, and Hooning, MJ
Abstract: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. We aimed to assess the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations of treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR(95%CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR(95%CI) :1.30 (1.09-1.56)]. In conclusion, systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk. (Main MS: 3201 words).
Published: 2023

48. Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Author: Morra, A, Schreurs, MAC, Andrulis, IL, Anton-Culver, H, Augustinsson, A, Beckmann, MW, Behrens, S, Bojesen, SE, Bolla, MK, Brauch, H, Broeks, A, Buys, SS, Camp, NJ, Castelao, JE, Cessna, MH, Chang-Claude, J, Chung, WK, Colonna, S, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Dennis, J, Devilee, P, Doerk, T, Dunning, AM, Dwek, M, Easton, DF, Eccles, DM, Eriksson, M, Evans, DG, Fasching, PA, Fehm, TN, Figueroa, JD, Flyger, H, Gabrielson, M, Gago-Dominguez, M, Garcia-Closas, M, Garcia-Saenz, JA, Genkinger, JA, Grassmann, F, Guendert, M, Hahnen, E, Haiman, C, Hamann, U, Harrington, PA, Hartikainen, JM, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Jakubowska, A, Janni, W, Jernstroem, H, John, EM, Johnson, N, Jones, ME, Kristensen, VN, Kurian, AW, Lambrechts, D, Le Marchand, L, Lindblom, A, Lubinski, J, Lux, MP, Mannermaa, A, Mavroudis, D, Mulligan, AM, Muranen, TA, Nevanlinna, H, Nevelsteen, I, Neven, P, Newman, WG, Obi, N, Offit, K, Olshan, AF, Park-Simon, T-W, Patel, A, Peterlongo, P, Phillips, K-A, Plaseska-Karanfilska, D, Polley, EC, Presneau, N, Pylkas, K, Rack, B, Radice, P, Rashid, MU, Rhenius, V, Robson, M, Romero, A, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schuetze, S, Scott, C, Shah, MT, Smichkoska, S, Southey, MC, Tapper, WJ, Teras, LR, Tollenaar, RAEM, Tomczyk, K, Tomlinson, I, Troester, M, Vachon, C, van Veen, E, Wang, Q, Wendt, C, Wildiers, H, Winqvist, RA, Ziogas, A, Hall, P, Pharoah, PDP, Adank, M, Hollestelle, A, Schmidt, MK, Hooning, MJ, Morra, A, Schreurs, MAC, Andrulis, IL, Anton-Culver, H, Augustinsson, A, Beckmann, MW, Behrens, S, Bojesen, SE, Bolla, MK, Brauch, H, Broeks, A, Buys, SS, Camp, NJ, Castelao, JE, Cessna, MH, Chang-Claude, J, Chung, WK, Colonna, S, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Dennis, J, Devilee, P, Doerk, T, Dunning, AM, Dwek, M, Easton, DF, Eccles, DM, Eriksson, M, Evans, DG, Fasching, PA, Fehm, TN, Figueroa, JD, Flyger, H, Gabrielson, M, Gago-Dominguez, M, Garcia-Closas, M, Garcia-Saenz, JA, Genkinger, JA, Grassmann, F, Guendert, M, Hahnen, E, Haiman, C, Hamann, U, Harrington, PA, Hartikainen, JM, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Jakubowska, A, Janni, W, Jernstroem, H, John, EM, Johnson, N, Jones, ME, Kristensen, VN, Kurian, AW, Lambrechts, D, Le Marchand, L, Lindblom, A, Lubinski, J, Lux, MP, Mannermaa, A, Mavroudis, D, Mulligan, AM, Muranen, TA, Nevanlinna, H, Nevelsteen, I, Neven, P, Newman, WG, Obi, N, Offit, K, Olshan, AF, Park-Simon, T-W, Patel, A, Peterlongo, P, Phillips, K-A, Plaseska-Karanfilska, D, Polley, EC, Presneau, N, Pylkas, K, Rack, B, Radice, P, Rashid, MU, Rhenius, V, Robson, M, Romero, A, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schuetze, S, Scott, C, Shah, MT, Smichkoska, S, Southey, MC, Tapper, WJ, Teras, LR, Tollenaar, RAEM, Tomczyk, K, Tomlinson, I, Troester, M, Vachon, C, van Veen, E, Wang, Q, Wendt, C, Wildiers, H, Winqvist, RA, Ziogas, A, Hall, P, Pharoah, PDP, Adank, M, Hollestelle, A, Schmidt, MK, and Hooning, MJ
Abstract: BACKGROUND: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. AIM: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. METHODS: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. RESULTS: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)]. CONCLUSION: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.
Published: 2023

49. A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry

Author: Middha, PK, Wang, X, Behrens, S, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Auer, PL, Augustinsson, A, Baert, T, Freeman, LEB, Becher, H, Beckmann, MW, Benitez, J, Bojesen, SE, Brauch, H, Brenner, H, Brooks-Wilson, A, Campa, D, Canzian, F, Carracedo, A, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Cordina-Duverger, E, Couch, FJ, Cox, A, Cross, SS, Czene, K, Dossus, L, Dugue, P-A, Eliassen, AH, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Gabrielson, M, Gago-Dominguez, M, Giles, GG, Gonzalez-Neira, A, Grassmann, F, Grundy, A, Guenel, P, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hankinson, SE, Harkness, EF, Holleczek, B, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Hunter, DJ, Ingvar, C, Isaksson, K, Jernstroem, H, John, EM, Jones, ME, Kaaks, R, Keeman, R, Kitahara, CM, Ko, Y-D, Koutros, S, Kurian, AW, Lacey, JV, Lambrechts, D, Larson, NL, Larsson, S, Le Marchand, L, Lejbkowicz, F, Li, S, Linet, M, Lissowska, J, Martinez, ME, Maurer, T, Mulligan, AM, Mulot, C, Murphy, RA, Newman, WG, Nielsen, SF, Nordestgaard, BG, Norman, A, O'Brien, KM, Olson, JE, Patel, AV, Prentice, R, Rees-Punia, E, Rennert, G, Rhenius, V, Ruddy, KJ, Sandler, DP, Scott, CG, Shah, MT, Shu, X-O, Smeets, A, Southey, MC, Stone, J, Tamimi, RM, Taylor, JA, Teras, LR, Tomczyk, K, Troester, MA, Truong, T, Vachon, CM, Wang, SS, Weinberg, CR, Wildiers, H, Willett, W, Winham, SJ, Wolk, A, Yang, X, Zamora, MP, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Garcia-Closas, M, Schmidt, MK, Kraft, P, Milne, RL, Lindstroem, S, Easton, DF, Chang-Claude, J, Middha, PK, Wang, X, Behrens, S, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Auer, PL, Augustinsson, A, Baert, T, Freeman, LEB, Becher, H, Beckmann, MW, Benitez, J, Bojesen, SE, Brauch, H, Brenner, H, Brooks-Wilson, A, Campa, D, Canzian, F, Carracedo, A, Castelao, JE, Chanock, SJ, Chenevix-Trench, G, Cordina-Duverger, E, Couch, FJ, Cox, A, Cross, SS, Czene, K, Dossus, L, Dugue, P-A, Eliassen, AH, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Gabrielson, M, Gago-Dominguez, M, Giles, GG, Gonzalez-Neira, A, Grassmann, F, Grundy, A, Guenel, P, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hankinson, SE, Harkness, EF, Holleczek, B, Hoppe, R, Hopper, JL, Houlston, RS, Howell, A, Hunter, DJ, Ingvar, C, Isaksson, K, Jernstroem, H, John, EM, Jones, ME, Kaaks, R, Keeman, R, Kitahara, CM, Ko, Y-D, Koutros, S, Kurian, AW, Lacey, JV, Lambrechts, D, Larson, NL, Larsson, S, Le Marchand, L, Lejbkowicz, F, Li, S, Linet, M, Lissowska, J, Martinez, ME, Maurer, T, Mulligan, AM, Mulot, C, Murphy, RA, Newman, WG, Nielsen, SF, Nordestgaard, BG, Norman, A, O'Brien, KM, Olson, JE, Patel, AV, Prentice, R, Rees-Punia, E, Rennert, G, Rhenius, V, Ruddy, KJ, Sandler, DP, Scott, CG, Shah, MT, Shu, X-O, Smeets, A, Southey, MC, Stone, J, Tamimi, RM, Taylor, JA, Teras, LR, Tomczyk, K, Troester, MA, Truong, T, Vachon, CM, Wang, SS, Weinberg, CR, Wildiers, H, Willett, W, Winham, SJ, Wolk, A, Yang, X, Zamora, MP, Zheng, W, Ziogas, A, Dunning, AM, Pharoah, PDP, Garcia-Closas, M, Schmidt, MK, Kraft, P, Milne, RL, Lindstroem, S, Easton, DF, and Chang-Claude, J
Abstract: BACKGROUND: Genome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. METHODS: Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. RESULTS: Assuming a 1 × 10-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). CONCLUSIONS: Overall, the contribution of G×E interactions to the heritability of breast cancer is very small. At the population level, multiplicative G×E interactions do not make an important contribution to risk prediction in breast cancer.
Published: 2023

50. Downstream Effects: Impact of Antibiotic Pollution on an Aquatic Host-parasite Interaction

Author: Melchiorre, Hannah G, Gutierrez, Stephanie O, Minchella, Dennis J, Vannatta, Jing Trevor, Melchiorre, Hannah G, Gutierrez, Stephanie O, Minchella, Dennis J, and Vannatta, Jing Trevor
Abstract: The global increase in antibiotic use has led to contamination of freshwater environments. Despite the identified impacts of antibiotics on humans and wildlife, the effect of antibiotics on host–parasite life cycles in freshwater is relatively unexplored. In the current study, we utilize the trematode parasite Schistosoma mansoni, and its snail intermediate host, Biomphalaria glabrata, to investigate the influence of an ecologically relevant antibiotic concentration on the life history characteristics of both parasite and host. Our results demonstrate that antibiotics not only accelerate parasite development time, but also increase host reproduction and delay parasite-induced host castration. Using a mathematical model, we suggest that life history alterations associated with antibiotics are likely to increase parasite transmission and disease burden. Our study suggests that antibiotic pollution could impact freshwater ecosystems by influencing host–parasite dynamics and potentially increase the burden of schistosomiasis in endemic regions.
Published: 2023

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Publication Type

Journal

Database

Publisher

2,506 results on '"Dennis, J."'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources