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3,951 results on '"Michel, G."'

7. Hope for Creation: Missional Responses to Environmental and Human Calamities

Author

Jonathan J. Bonk, Michel G. Distefano, J. Nelson Jennings, Jinbong Kim, Jae Hoon Lee, Jonathan J. Bonk, Michel G. Distefano, J. Nelson Jennings, Jinbong Kim, Jae Hoon Lee and Jonathan J. Bonk, Michel G. Distefano, J. Nelson Jennings, Jinbong Kim, Jae Hoon Lee, Jonathan J. Bonk, Michel G. Distefano, J. Nelson Jennings, Jinbong Kim, Jae Hoon Lee

Published
2024

8. Tackling Infectious Diseases with Rapid Molecular Diagnosis and Innovative Prevention

Author

Rabeea F. Omar, Maurice Boissinot, Ann Huletsky, and Michel G. Bergeron

Subjects
infectious diseases, prevention, diagnosis, antimicrobial resistance, innovation, technology transfer, Other systems of medicine, RZ201-999
Abstract

Infectious diseases (IDs) are a leading cause of death. The diversity and adaptability of microbes represent a continuing risk to health. Combining vision with passion, our transdisciplinary medical research team has been focussing its work on the better management of infectious diseases for saving human lives over the past five decades through medical discoveries and innovations that helped change the practice of medicine. The team used a multiple-faceted and integrated approach to control infectious diseases through fundamental discoveries and by developing innovative prevention tools and rapid molecular diagnostic tests to fulfill the various unmet needs of patients and health professionals in the field of ID. In this article, as objectives, we put in context two main research areas of ID management: innovative infection prevention that is woman-controlled, and the rapid molecular diagnosis of infection and resistance. We also explain how our transdisciplinary approach encompassing specialists from diverse fields ranging from biology to engineering was instrumental in achieving success. Furthermore, we discuss our vision of the future for translational research to better tackle IDs.

Published
2024
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9. Comparison of rectal swabs and fecal samples for the detection of Clostridioides difficile infections with a new in-house PCR assay

Author

Ann Huletsky, Vivian G. Loo, Yves Longtin, Jean Longtin, Sylvie Trottier, Cécile L. Tremblay, Rodica Gilca, Christian Lavallée, Éliel Brochu, Ève Bérubé, Martine Bastien, Marthe Bernier, Martin Gagnon, Johanne Frenette, Julie Bestman-Smith, Louise Deschênes, and Michel G. Bergeron

Subjects
Clostridioides difficile, diagnostics, molecular methods, rectal swabs, Microbiology, QR1-502
Abstract

ABSTRACT The detection of Clostridioides difficile infections (CDI) relies on testing the stool of patients by toxin antigen detection or PCR methods. Although PCR and antigenic methods have significantly reduced the time to results, delays in stool collection can significantly add to the turnaround time. The use of rectal swabs to detect C. difficile could considerably reduce the time to diagnosis of CDI. We developed a new rapid PCR assay for the detection of C. difficile and evaluated this PCR assay on both stool and rectal swab specimens. We recruited a total of 623 patients suspected of C. difficile infection. Stool samples and rectal swabs were collected from each patient and tested by our PCR assay. Stool samples were also tested by the cell cytotoxicity neutralization assay (CCNA) as a reference. The PCR assay detected C. difficile in 60 stool specimens and 61 rectal swabs for the 64 patients whose stool samples were positive for C. difficile by CCNA. The PCR assay detected an additional 35 and 36 stool and rectal swab specimens positive for C. difficile, respectively, for sensitivity with stools and rectal swabs of 93.8% and 95.3%, specificity of 93.7% and 93.6%, positive predictive values of 63.2% and 62.9%, and negative predictive values of 99.2% and 99.4%. Detection of C. difficile using PCR on stools or rectal swabs yielded reliable and similar results. The use of PCR tests on rectal swabs could reduce turnaround time for CDI detection, thus improving CDI management and control of C. difficile transmission.IMPORTANCEClostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, resulting in high morbidity, mortality, and economic burden. In clinical laboratories, CDI testing is currently performed on stool samples collected from patients with diarrhea. However, the diagnosis of CDI can be delayed by the time required to collect stool samples. Barriers to sample collection could be overcome by using a rectal swab instead of a stool sample. Our study showed that CDI can be identified rapidly and reliably by a new PCR assay developed in our laboratory on both stool and rectal swab specimens. The use of PCR tests on rectal swabs could reduce the time for the detection of CDI and improve the management of this infection. It should also provide a useful alternative for infection-control practitioners to better control the spread of C. difficile.

Published
2024
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12. Expanding the repertoire reveals recurrent, cryptic, and hematopoietic HLA class I minor histocompatibility antigens

Author

Fuchs, Kyra J., van de Meent, Marian, Honders, M. Willy, Khatri, Indu, Kester, Michel G. D., Koster, Eva A. S., Koutsoumpli, Georgia, de Ru, Arnoud H., van Bergen, Cornelis A. M., van Veelen, Peter A., ’t Hoen, Peter A. C., van Balen, Peter, van den Akker, Erik B., Veelken, J. Hendrik, Halkes, Constantijn J. M., Falkenburg, J. H. Frederik, and Griffioen, Marieke

Published
2024
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13. The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology

Author

STERN, LILY K., GRODIN, JUSTIN L., MAURER, MATHEW S., RUBERG, FREDERICK L., PATEL, AYAN R., KHOURI, MICHEL G., ROTH, LORI R., ARAS, MANDAR A., BHARDWAJ, ANJU, BHATTACHARYA, PRIYANKA, BRAILOVSKY, YEVGENIY, DRACHMAN, BRIAN M., EBONG, IMO A., FINE, NOWELL M., GAGGIN, HANNA, GOPAL, DEEPA, GRIFFIN, JAN, JUDGE, DANIEL, KIM, PAUL, MITCHELL, JOSHUA, MITTER, SUMEET S., MOHAN, RAJEEV C., RAMOS, HANNIA, REYENTOVICH, ALEX, SHEIKH, FAROOQ H., SPERRY, BRETT, CARTER, SPENCER, UREY, MARCUS, VAISHNAV, JOBAN, VEST, AMANDA R., KITTLESON, MICHELLE M., and PATEL, JIGNESH K.

Published
2024
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15. Long-term trajectories of densely reported depressive symptoms during an extended period of the COVID-19 pandemic in Switzerland: Social worries matter

Author

Probst-Hensch, N., Imboden, M., Jeong, A., Keidel, D., Vermes, T., Witzig, M., Cullati, S., Tancredi, S., Noor, N., Rodondi, P.-Y., Harju, E., Michel, G., Frank, I., Kahlert, C., Cusini, A., Rodondi, N., Chocano-Bedoya, P.O., Bardoczi, J.B., Stuber, M.J., Vollrath, F., Fehr, J., Frei, A., Kaufmann, M., Geigges, M., von Wyl, V., Puhan, M.A., Albanese, E., Crivelli, L., and Lovison, G.F.

Published
2024
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17. Human CD34+-derived complete plasmacytoid and conventional dendritic cell vaccine effectively induces antigen-specific CD8+ T cell and NK cell responses in vitro and in vivo

Author

van Eck van der Sluijs, Jesper, van Ens, Diede, Brummelman, Jolanda, Heister, Daan, Sareen, Aastha, Truijen, Lisa, van Ingen Schenau, Dorette S., Heemskerk, Mirjam H. M., Griffioen, Marieke, Kester, Michel G. D., Schaap, Nicolaas P. M., Jansen, Joop H., van der Waart, Anniek B., Dolstra, Harry, and Hobo, Willemijn

Published
2023
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18. Enhancing outcomes: neurosurgical resection in brain metastasis patients with poor Karnofsky performance score - a comprehensive survival analysis

Author

Maria Goldberg, Michel G. Mondragon-Soto, Ghaith Altawalbeh, Lea Baumgart, Jens Gempt, Denise Bernhardt, Stephanie E. Combs, Bernhard Meyer, and Amir Kaywan Aftahy

Subjects
Karnofsky performance status, neurosurgical resection, brain metastases, overall survival, systemic tumor progression, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

BackgroundA reduced Karnofsky performance score (KPS) often leads to the discontinuation of surgical and adjuvant therapy, owing to a lack of evidence of survival and quality of life benefits. This study aimed to examine the clinical and treatment outcomes of patients with KPS < 70 after neurosurgical resection and identify prognostic factors associated with better survival.MethodsPatients with a preoperative KPS < 70 who underwent surgical resection for newly diagnosed brain metastases (BM) between 2007 and 2020 were retrospectively analyzed. The KPS, age, sex, tumor localization, cumulative tumor volume, number of lesions, extent of resection, prognostic assessment scores, adjuvant radiotherapy and systemic therapy, and presence of disease progression were analyzed. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with better survival. Survival > 3 months was considered favorable and ≤ 3 months as poor.ResultsA total of 140 patients were identified. Median overall survival was 5.6 months (range 0-58). There was no difference in the preoperative KPS between the groups of > 3 and ≤ 3 months (50; range, 20–60 vs. 50; range, 10–60, p = 0.077). There was a significant improvement in KPS after surgery in patients with a preoperative KPS of 20% (20 vs 40 ± 20, p = 0.048). In the other groups, no significant changes in KPS were observed. Adjuvant radiotherapy was associated with better survival (44 [84.6%] vs. 32 [36.4%]; hazard ratio [HR], 0.0363; confidence interval [CI], 0.197–0.670, p = 0.00199). Adjuvant chemotherapy and immunotherapy resulted in prolonged survival (24 [46.2%] vs. 12 [13.6%]; HR 0.474, CI 0.263–0.854, p = 0.013]. Systemic disease progression was associated with poor survival (36 [50%] vs. 71 [80.7%]; HR 5.975, CI 2.610–13.677, p < 0.001].ConclusionNeurosurgical resection is an appropriate treatment modality for patients with low KPS. Surgery may improve functional status and facilitate further tumor-specific treatment. Combined treatment with adjuvant radiotherapy and systemic therapy was associated with improved survival in this cohort of patients. Systemic tumor progression has been identified as an independent factor for a poor prognosis. There is almost no information regarding surgical and adjuvant treatment in patients with low KPS. Our paper provides novel data on clinical outcome and survival analysis of patients with BM who underwent surgical treatment.

Published
2024
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19. A systematic review of tools for predicting complications in patients with influenza-like illness

Author

Tania Marx, Nada Khelifi, Isabelle Xu, Laurie Ouellet, Annie Poirier, Benoit Huard, Myriam Mallet, Frédéric Bergeron, Maurice Boissinot, Michel G. Bergeron, and Simon Berthelot

Subjects
Influenza-like illness, Risk stratification tool, Outpatient, Hospitalization, Mortality, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Objective: To identify tools that predict the risk of complications for patients presenting to an outpatient clinic or an emergency department (ED) with influenza-like illness. Methods: We searched Medline, Embase, Cochrane Library and CINAHL from inception to July 2023. We included articles reporting on the derivation or validation of a score or algorithm used to stratify the risk of hospitalization or mortality among patients with influenza-like illness in the ED or outpatient clinic. Results: Twelve articles reporting on eight scores and six predictive models were identified. For predicting the need for hospitalization, the area under the curve (AUC) of the PMEWS and the CURB-65 ranged respectively from 0.76 to 0.94, and 0.65 to 0.88. The Community Assessment Tool had an AUC of 0.62. For predicting inpatient mortality, AUC was 0.66 for PMEWS and 0.79 for CURB-65, 0.79 for the SIRS criteria and 0.86 for the qSOFA score. Two scores were developed without external validation during the Covid-19 pandemic. The CovHos score and the Canadian Covid discharge score had an AUC ranged from 0.70 to 0.91. The predictive models performed adequately (AUC from 0.76 to 0.92) but will require external validation for clinical use. Tool diversity and study population heterogeneity precluded meta-analysis. Conclusion: Although the CURB, PMEWS and qSOFA scores appear to predict accurately the risk of complications of influenza-like illness, none were reliable enough to justify their widespread ED use. Refinement of an existing tool or development of a new tool to optimize the management of these patients is needed.

Published
2024
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24. Appropriate and inappropriate ICD shocks in patients with LVADs: Prevalence, associated factors, and etiologies

Author

Andreae, Andrew, Black-Maier, Eric, Arps, Kelly, Kobe, Elizabeth, Johnson, Trevor, Shrader, Peter, Holmes, DaJuanicia, Towery, Emily, Sun, Albert, Friedman, Daniel J., Koontz, Jason, Schroder, Jacob, Milano, Carmelo, Khouri, Michel G., Katz, Jason N., Agarwal, Richa, Russell, Stuart D., Pokorney, Sean, Daubert, James, and Piccini, Jonathan

Published
2024
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29. Relative cerebral blood volume as response predictor in the treatment of recurrent glioblastoma with anti-angiogenic therapy

Author

Breda-Yepes, Michele, Rodríguez-Hernández, Luis A., Gómez-Figueroa, Enrique, Mondragón-Soto, Michel G., Arellano-Flores, Gerardo, Hernández-Hernández, Alan, Rodríguez-Rubio, Héctor A., Martínez, Pablo, Reyes-Moreno, Ignacio, Álvaro-Heredia, Juan A., Gutiérrez Aceves, Guillermo A., Villanueva-Castro, Eliezer, Sangrador-Deitos, Marcos V., Alonso-Vanegas, Mario, Guerrero-Juárez, Vicente, and González-Aguilar, Alberto

Published
2023
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30. Broadly applicable TCR-based therapy for multiple myeloma targeting the immunoglobulin J chain

Author

Miranda H. Meeuwsen, Anne K. Wouters, Tassilo L. A. Wachsmann, Renate S. Hagedoorn, Michel G. D. Kester, Dennis F. G. Remst, Dirk M. van der Steen, Arnoud H. de Ru, Els P. van Hees, Martijn Kremer, Marieke Griffioen, Peter A. van Veelen, J. H. Frederik Falkenburg, and Mirjam H. M. Heemskerk

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The immunoglobulin J chain (Jchain) is highly expressed in the majority of multiple myeloma (MM), and Jchain-derived peptides presented in HLA molecules may be suitable antigens for T-cell therapy of MM. Methods Using immunopeptidomics, we identified Jchain-derived epitopes presented by MM cells, and pHLA tetramer technology was used to isolate Jchain-specific T-cell clones. Results We identified T cells specific for Jchain peptides presented in HLA-A1, -A24, -A3, and -A11 that recognized and lysed JCHAIN-positive MM cells. TCRs of the most promising T-cell clones were sequenced, cloned into retroviral vectors, and transferred to CD8 T cells. Jchain TCR T cells recognized target cells when JCHAIN and the appropriate HLA restriction alleles were expressed, while JCHAIN or HLA-negative cells, including healthy subsets, were not recognized. Patient-derived JCHAIN-positive MM samples were also lysed by Jchain TCR T cells. In a preclinical in vivo model for established MM, Jchain-A1, -A24, -A3, and -A11 TCR T cells strongly eradicated MM cells, which resulted in 100-fold lower tumor burden in Jchain TCR versus control-treated mice. Conclusions We identified TCRs targeting Jchain-derived peptides presented in four common HLA alleles. All four TCRs demonstrated potent preclinical anti-myeloma activity, encouraging further preclinical testing and ultimately clinical development.

Published
2023
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31. Pressures do not equal volumes: implications for heart failure management in patients with CardioMEMS

Author

Muhammad Shahzeb Khan, Michel G. Khouri, Leilani Gomez, and Marat Fudim

Subjects
Heart failure, Pressure, Volume, CardioMEMS, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Pulmonary arterial pressures are often used as surrogates for intravascular blood volume. However, the relationship between pressure and volume remains controversial. To contextualize and provide concrete examples and impact on clinical management, we report two cases of heart failure (one in heart failure with reduced ejection fraction and one in heart failure with preserved ejection fraction) where pressure‐based measurements did not accurately represent the intravascular status and affected clinical management.

Published
2023
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32. Oral Loading of Phenobarbital to Achieve Therapeutic Effects in Pediatric Patients with Acute Repetitive Seizures

Author

Jemima Grace D. Fronda, Mel Michel G. Villaluz, and Cristina M. Cruz-Urbi

Subjects
phenobarbital, pediatrics, administration, oral, seizures, developing countries, Internal medicine, RC31-1245, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Purpose Intravenous phenobarbital has not been available at our institution since 2019. This study aimed to determine the effectiveness of oral phenobarbital loading at a dose of 15 to 20 mg/kg to achieve therapeutic serum levels and clinical seizure control in pediatric patients with acute repetitive seizures. Methods This is a retrospective single-center review of the medical records of pediatric patients admitted for acute repetitive seizures (from January 2019 to June 2022) at the Philippine Children’s Medical Center who were given an oral phenobarbital loading dose of 15 to 20 mg/kg with serum level measurements taken within 48 hours after oral loading. Results Eleven patients were given a single oral phenobarbital loading dose of 15 to 20 mg/kg, while 14 were given two doses of 10 mg/kg 12 hours apart. All 25 patients achieved therapeutic serum levels within 48 hours post-loading. Higher serum levels were seen at 48 hours (median, 19.8 μg/mL at 24 hours vs. 24.4 μg/mL at 48 hours). This difference was statistically significant at 5% (P=0.023), and the majority achieved adequate seizure control without requiring additional anti-seizure medications (76%). Transient drowsiness was the most commonly documented adverse effect. Conclusion Oral loading of phenobarbital at a dose of 15 to 20 mg/kg given as a single dose or in two divided doses is an effective and safe alternative to achieve therapeutic serum levels and adequate clinical seizure control at 24 hours post-loading. This may be a promising and useful intervention at centers without available intravenous phenobarbital.

Published
2023
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36. Navigating Post-Operative Outcomes: A Comprehensive Reframing of an Original Graded Prognostic Assessment in Patients with Brain Metastases

Author

Maria Goldberg, Michel G. Mondragon-Soto, Laura Dieringer, Ghaith Altawalbeh, Paul Pöser, Lea Baumgart, Benedikt Wiestler, Jens Gempt, Bernhard Meyer, and Amir Kaywan Aftahy

Subjects
GPA, brain metastasis, prognostic assessment, rest tumor volume, surgery, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Graded Prognostic Assessment (GPA) has been proposed for various brain metastases (BMs) tailored to the primary histology and molecular profiles. However, it does not consider whether patients have been operated on or not and does not include surgical outcomes as prognostic factors. The residual tumor burden (RTB) is a strong predictor of overall survival. We validated the GPA score and introduced “volumetric GPA” in the largest cohort of operated patients and further explored the role of RTB as an additional prognostic factor. Methods: A total of 630 patients with BMs between 2007 and 2020 were included. The four GPA components were analyzed. The validity of the original score was assessed using Cox regression, and a modified index incorporating RTB was developed by comparing the accuracy, sensitivity, specificity, F1-score, and AUC parameters. Results: GPA categories showed an association with survival: age (p < 0.001, hazard ratio (HR) 2.9, 95% confidence interval (CI) 2.5–3.3), Karnofsky performance status (KPS) (p < 0.001, HR 1.3, 95% CI 1.2–1.5), number of BMs (p = 0.019, HR 1.4, 95% CI 1.1–1.8), and the presence of extracranial manifestation (p < 0.001, HR 3, 95% CI 1.6–2.5). The median survival for GPA 0–1 was 4 months; for GPA 1.5–2, it was 12 months; for GPA 2.5–3, it was 21 months; and for GPA 3.5–4, it was 38 months (p < 0.001). RTB was identified as an independent prognostic factor. A cut-off of 2 cm3 was used for further analysis, which showed a median survival of 6 months (95% CI 4–8) vs. 13 months (95% CI 11–14, p < 0.001) for patients with RTB > 2 cm3 and 3, respectively. RTB was added as an additional component for a modified volumetric GPA score. The survival rates with the modified GPA score were: GPA 0–1: 4 months, GPA 1.5–2: 7 months, GPA 2.5–3: 18 months, and GPA 3.5–4: 34 months. Both scores showed good stratification, with the new score showed a trend towards better discrimination in patients with more favorable prognoses. Conclusion: The prognostic value of the original GPA was confirmed in our cohort of patients who underwent surgery for BM. The RTB was identified as a parameter of high prognostic significance and was incorporated into an updated “volumetric GPA”. This score provides a novel tool for prognosis and clinical decision making in patients undergoing surgery. This method may be useful for stratification and patient selection for further treatment and in future clinical trials.

Published
2024
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37. Gut metagenome profile of the Nunavik Inuit youth is distinct from industrial and non-industrial counterparts

Author

Jehane Y. Abed, Thibaud Godon, Fadwa Mehdaoui, Pier-Luc Plante, Maurice Boissinot, Michel G. Bergeron, Richard E. Bélanger, Gina Muckle, Natalia Poliakova, Pierre Ayotte, Jacques Corbeil, and Elsa Rousseau

Subjects
Biology (General), QH301-705.5
Abstract

Nunavik Inuit gut microbiome retains a high intra-individual and lower inter-individual diversity, and is distinct from the gut microbiome of non-industrial and industrial populations

Published
2022
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38. Transcriptome-wide and stratified genomic structural equation modeling identify neurobiological pathways shared across diverse cognitive traits

Author

Andrew D. Grotzinger, Javier de la Fuente, Gail Davies, Michel G. Nivard, and Elliot M. Tucker-Drob

Subjects
Science
Abstract

High genetic overlap across traits requires methods that can be used to disentangle shared and unique biological pathways. Here, the authors introduce TSEM, a multivariate method for examining tissue-specific gene expression, and apply it to identify genes associated with cognitive traits.

Published
2022
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39. The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder: A Two-Sample Mendelian Randomization and Population-Based Sibling Comparison Study

Author

Maihofer, Adam X., Choi, Karmel W., Coleman, Jonathan R.I., Daskalakis, Nikolaos P., Denckla, Christy A., Ketema, Elizabeth, Morey, Rajendra A., Polimanti, Renato, Ratanatharathorn, Andrew, Torres, Katy, Wingo, Aliza P., Zai, Clement C., Aiello, Allison E., Almli, Lynn M., Amstadter, Ananda B., Andersen, Soren B., Andreassen, Ole A., Arbisi, Paul A., Ashley-Koch, Allison E., Austin, S. Bryn, Avdibegovic, Esmina, Borglum, Anders D., Babic, Dragan, Bækvad-Hansen, Marie, Baker, Dewleen G., Beckham, Jean C., Bierut, Laura J., Bisson, Jonathan I., Boks, Marco P., Bolger, Elizabeth A., Bradley, Bekh, Brashear, Meghan, Breen, Gerome, Bryant, Richard A., Bustamante, Angela C., Bybjerg-Grauholm, Jonas, Calabrese, Joseph R., Caldas-de-Almeida, Jose Miguel, Chen, Chia-Yen, Dale, Anders M., Dalvie, Shareefa, Deckert, Jürgen, Delahanty, Douglas L., Dennis, Michelle F., Disner, Seth G., Domschke, Katharina, Duncan, Laramie E., Kulenovic, Alma Dzubur, Erbes, Christopher R., Evans, Alexandra, Farrer, Lindsay A., Feeny, Norah C., Flory, Janine D., Forbes, David, Franz, Carol E., Galea, Sandro, Garrett, Melanie E., Gautam, Aarti, Gelaye, Bizu, Gelernter, Joel, Geuze, Elbert, Gillespie, Charles F., Uka, Aferdita Goci, Gordon, Scott D., Guffanti, Guia, Hammamieh, Rasha, Hauser, Michael A., Heath, Andrew C., Hemmings, Sian M.J., Hougaard, David Michael, Jakovljevic, Miro, Jett, Marti, Johnson, Eric Otto, Jones, Ian, Jovanovic, Tanja, Qin, Xue-Jun, Karstoft, Karen-Inge, Kaufman, Milissa L., Kessler, Ronald C., Khan, Alaptagin, Kimbrel, Nathan A., King, Anthony P., Koen, Nastassja, Kranzler, Henry R., Kremen, William S., Lawford, Bruce R., Lebois, Lauren A.M., Lewis, Catrin, Liberzon, Israel, Linnstaedt, Sarah D., Logue, Mark W., Lori, Adriana, Lugonja, Bozo, Luykx, Jurjen J., Lyons, Michael J., Maples-Keller, Jessica L., Marmar, Charles, Martin, Nicholas G., Maurer, Douglas, Mavissakalian, Matig R., McFarlane, Alexander, McGlinchey, Regina E., McLaughlin, Katie A., McLean, Samuel A., Mehta, Divya, Mellor, Rebecca, Michopoulos, Vasiliki, Milberg, William, Miller, Mark W., Morris, Charles Phillip, Mors, Ole, Mortensen, Preben Bo, Nelson, Elliot C., Nordentoft, Merete, Norman, Sonya B., O’Donnell, Meaghan, Orcutt, Holly K., Panizzon, Matthew S., Peters, Edward S., Peterson, Alan L., Peverill, Matthew, Pietrzak, Robert H., Polusny, Melissa A., Rice, John P., Risbrough, Victoria B., Roberts, Andrea L., Rothbaum, Alex O., Rothbaum, Barbara O., Roy-Byrne, Peter, Ruggiero, Kenneth J., Rung, Ariane, Rutten, Bart P.F., Saccone, Nancy L., Sanchez, Sixto E., Schijven, Dick, Seedat, Soraya, Seligowski, Antonia V., Seng, Julia S., Sheerin, Christina M., Silove, Derrick, Smith, Alicia K., Smoller, Jordan W., Sponheim, Scott R., Stein, Dan J., Stevens, Jennifer S., Teicher, Martin H., Thompson, Wesley K., Trapido, Edward, Uddin, Monica, Ursano, Robert J., Luella van den Heuvel, Leigh, Van Hooff, Miranda, Vermetten, Eric, Vinkers, Christiaan, Voisey, Joanne, Wang, Yunpeng, Wang, Zhewu, Werge, Thomas, Williams, Michelle A., Williamson, Douglas E., Winternitz, Sherry, Wolf, Christiane, Wolf, Erika J., Yehuda, Rachel, Young, Keith A., Young, Ross McD., Zhao, Hongyu, Zoellner, Lori A., Haas, Magali, Lasseter, Heather, Provost, Allison C., Salem, Rany M., Sebat, Jonathan, Shaffer, Richard, Wu, Tianying, Ripke, Stephan, Daly, Mark J., Ressler, Kerry J., Koenen, Karestan C., Stein, Murray B., Nievergelt, Caroline M., Wendt, Frank R., Garcia-Argibay, Miguel, Cabrera-Mendoza, Brenda, Valdimarsdóttir, Unnur A., Nivard, Michel G., Larsson, Henrik, Mattheisen, Manuel, and Meier, Sandra M.

Published
2023
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43. Estimating effects of parents’ cognitive and non-cognitive skills on offspring education using polygenic scores

Author

Perline A. Demange, Jouke Jan Hottenga, Abdel Abdellaoui, Espen Moen Eilertsen, Margherita Malanchini, Benjamin W. Domingue, Emma Armstrong-Carter, Eveline L. de Zeeuw, Kaili Rimfeld, Dorret I. Boomsma, Elsje van Bergen, Gerome Breen, Michel G. Nivard, and Rosa Cheesman

Subjects
Science
Abstract

Understanding how parents’ cognitive and non-cognitive skills influence their children’s educational trajectories is important for educational, family and economic policy. Here, the authors investigate parental influence on children’s education using genetic approaches.

Published
2022
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44. Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

Author

Howe, Laurence J., Nivard, Michel G., Morris, Tim T., Hansen, Ailin F., Rasheed, Humaira, Cho, Yoonsu, Chittoor, Geetha, Ahlskog, Rafael, Lind, Penelope A., Palviainen, Teemu, van der Zee, Matthijs D., Cheesman, Rosa, Mangino, Massimo, Wang, Yunzhang, Li, Shuai, Klaric, Lucija, Ratliff, Scott M., Bielak, Lawrence F., Nygaard, Marianne, Giannelis, Alexandros, Willoughby, Emily A., Reynolds, Chandra A., Balbona, Jared V., Andreassen, Ole A., Ask, Helga, Baras, Aris, Bauer, Christopher R., Boomsma, Dorret I., Campbell, Archie, Campbell, Harry, Chen, Zhengming, Christofidou, Paraskevi, Corfield, Elizabeth, Dahm, Christina C., Dokuru, Deepika R., Evans, Luke M., de Geus, Eco J. C., Giddaluru, Sudheer, Gordon, Scott D., Harden, K. Paige, Hill, W. David, Hughes, Amanda, Kerr, Shona M., Kim, Yongkang, Kweon, Hyeokmoon, Latvala, Antti, Lawlor, Deborah A., Li, Liming, Lin, Kuang, Magnus, Per, Magnusson, Patrik K. E., Mallard, Travis T., Martikainen, Pekka, Mills, Melinda C., Njølstad, Pål Rasmus, Overton, John D., Pedersen, Nancy L., Porteous, David J., Reid, Jeffrey, Silventoinen, Karri, Southey, Melissa C., Stoltenberg, Camilla, Tucker-Drob, Elliot M., Wright, Margaret J., Hewitt, John K., Keller, Matthew C., Stallings, Michael C., Lee, James J., Christensen, Kaare, Kardia, Sharon L. R., Peyser, Patricia A., Smith, Jennifer A., Wilson, James F., Hopper, John L., Hägg, Sara, Spector, Tim D., Pingault, Jean-Baptiste, Plomin, Robert, Havdahl, Alexandra, Bartels, Meike, Martin, Nicholas G., Oskarsson, Sven, Justice, Anne E., Millwood, Iona Y., Hveem, Kristian, Naess, Øyvind, Willer, Cristen J., Åsvold, Bjørn Olav, Koellinger, Philipp D., Kaprio, Jaakko, Medland, Sarah E., Walters, Robin G., Benjamin, Daniel J., Turley, Patrick, Evans, David M., Davey Smith, George, Hayward, Caroline, Brumpton, Ben, Hemani, Gibran, and Davies, Neil M.

Published
2022
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45. Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis

Author

Grotzinger, Andrew D., Mallard, Travis T., Akingbuwa, Wonuola A., Ip, Hill F., Adams, Mark J., Lewis, Cathryn M., McIntosh, Andrew M., Grove, Jakob, Dalsgaard, Søren, Lesch, Klaus-Peter, Strom, Nora, Meier, Sandra M., Mattheisen, Manuel, Børglum, Anders D., Mors, Ole, Breen, Gerome, Lee, Phil H., Kendler, Kenneth S., Smoller, Jordan W., Tucker-Drob, Elliot M., and Nivard, Michel G.

Published
2022
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47. Identifying the Common Genetic Basis of Antidepressant Response

Author

Oliver Pain, Karen Hodgson, Vassily Trubetskoy, Stephan Ripke, Victoria S. Marshe, Mark J. Adams, Enda M. Byrne, Adrian I. Campos, Tania Carrillo-Roa, Annamaria Cattaneo, Thomas D. Als, Daniel Souery, Mojca Z. Dernovsek, Chiara Fabbri, Caroline Hayward, Neven Henigsberg, Joanna Hauser, James L. Kennedy, Eric J. Lenze, Glyn Lewis, Daniel J. Müller, Nicholas G. Martin, Benoit H. Mulsant, Ole Mors, Nader Perroud, David J. Porteous, Miguel E. Rentería, Charles F. Reynolds, III, Marcella Rietschel, Rudolf Uher, Eleanor M. Wigmore, Wolfgang Maier, Naomi R. Wray, Katherine J. Aitchison, Volker Arolt, Bernhard T. Baune, Joanna M. Biernacka, Guido Bondolfi, Katharina Domschke, Masaki Kato, Qingqin S. Li, Yu-Li Liu, Alessandro Serretti, Shih-Jen Tsai, Gustavo Turecki, Richard Weinshilboum, Andrew M. McIntosh, Cathryn M. Lewis, Siegfried Kasper, Joseph Zohar, Stuart Montgomery, Diego Albani, Gianluigi Forloni, Panagiotis Ferentinos, Dan Rujescu, Julien Mendlewicz, Manuel Mattheisen, Maciej Trzaskowski, Abdel Abdellaoui, Esben Agerbo, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Tim B. Bigdeli, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Jonathan R.I. Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Ian J. Deary, Franziska Degenhardt, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Andreas J. Forstner, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Hougaard, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E. Medland, Divya Mehta, Christel M. Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Michael J. Owen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Jianxin Shi, Stanley I. Shyn, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, André G. Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H. Witt, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Klaus Berger, Dorret I. Boomsma, Sven Cichon, Udo Dannlowski, E.J.C. de Geus, J. Raymond DePaulo, Enrico Domenici, Tõnu Esko, Hans J. Grabe, Steven P. Hamilton, Andrew C. Heath, Kenneth S. Kendler, Stefan Kloiber, Susanne Lucae, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M. Nöthen, Michael C. O’Donovan, Sara A. Paciga, Nancy L. Pedersen, Brenda W.J.H. Penninx, Roy H. Perlis, James B. Potash, Martin Preisig, Catherine Schaefer, Thomas G. Schulze, Jordan W. Smoller, Kari Stefansson, Henning Tiemeier, Henry Völzke, Myrna M. Weissman, Thomas Werge, Douglas F. Levinson, Gerome Breen, Anders D. Børglum, and Patrick F. Sullivan

Subjects
Antidepressant response, Depression, Genetics, GWAS, MDD, Polygenic score, Psychiatry, RC435-571
Abstract

Background: Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction. Methods: Genome-wide analysis of remission (nremit = 1852, nnonremit = 3299) and percentage improvement (n = 5218) was performed. Single nucleotide polymorphism–based heritability was estimated using genome-wide complex trait analysis. Genetic covariance with eight mental health phenotypes was estimated using polygenic scores/AVENGEME. Out-of-sample prediction of antidepressant response polygenic scores was assessed. Gene-level association analysis was performed using MAGMA and transcriptome-wide association study. Tissue, pathway, and drug binding enrichment were estimated using MAGMA. Results: Neither genome-wide association study identified genome-wide significant associations. Single nucleotide polymorphism–based heritability was significantly different from zero for remission (h2 = 0.132, SE = 0.056) but not for percentage improvement (h2 = −0.018, SE = 0.032). Better antidepressant response was negatively associated with genetic risk for schizophrenia and positively associated with genetic propensity for educational attainment. Leave-one-out validation of antidepressant response polygenic scores demonstrated significant evidence of out-of-sample prediction, though results varied in external cohorts. Gene-based analyses identified ETV4 and DHX8 as significantly associated with antidepressant response. Conclusions: This study demonstrates that antidepressant response is influenced by common genetic variation, has a genetic overlap schizophrenia and educational attainment, and provides a useful resource for future research. Larger sample sizes are required to attain the potential of genetics for understanding and predicting antidepressant response.

Published
2022
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49. Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms

Author

Jami, Eshim S., Hammerschlag, Anke R., Ip, Hill F., Allegrini, Andrea G., Benyamin, Beben, Border, Richard, Diemer, Elizabeth W., Jiang, Chang, Karhunen, Ville, Lu, Yi, Lu, Qing, Mallard, Travis T., Mishra, Pashupati P., Nolte, Ilja M., Palviainen, Teemu, Peterson, Roseann E., Sallis, Hannah M., Shabalin, Andrey A., Tate, Ashley E., Thiering, Elisabeth, Vilor-Tejedor, Natàlia, Wang, Carol, Zhou, Ang, Adkins, Daniel E., Alemany, Silvia, Ask, Helga, Chen, Qi, Corley, Robin P., Ehli, Erik A., Evans, Luke M., Havdahl, Alexandra, Hagenbeek, Fiona A., Hakulinen, Christian, Henders, Anjali K., Hottenga, Jouke Jan, Korhonen, Tellervo, Mamun, Abdullah, Marrington, Shelby, Neumann, Alexander, Rimfeld, Kaili, Rivadeneira, Fernando, Silberg, Judy L., van Beijsterveldt, Catharina E., Vuoksimaa, Eero, Whipp, Alyce M., Tong, Xiaoran, Andreassen, Ole A., Boomsma, Dorret I., Brown, Sandra A., Burt, S. Alexandra, Copeland, William, Dick, Danielle M., Harden, K. Paige, Harris, Kathleen Mullan, Hartman, Catharina A., Heinrich, Joachim, Hewitt, John K., Hopfer, Christian, Hypponen, Elina, Jarvelin, Marjo-Riitta, Kaprio, Jaakko, Keltikangas-Järvinen, Liisa, Klump, Kelly L., Krauter, Kenneth, Kuja-Halkola, Ralf, Larsson, Henrik, Lehtimäki, Terho, Lichtenstein, Paul, Lundström, Sebastian, Maes, Hermine H., Magnus, Per, Munafò, Marcus R., Najman, Jake M., Njølstad, Pål R., Oldehinkel, Albertine J., Pennell, Craig E., Plomin, Robert, Reichborn-Kjennerud, Ted, Reynolds, Chandra, Rose, Richard J., Smolen, Andrew, Snieder, Harold, Stallings, Michael, Standl, Marie, Sunyer, Jordi, Tiemeier, Henning, Wadsworth, Sally J., Wall, Tamara L., Whitehouse, Andrew J.O., Williams, Gail M., Ystrøm, Eivind, Nivard, Michel G., Bartels, Meike, and Middeldorp, Christel M.

Published
2022
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50. A novel phosphocholine‐mimetic inhibits a pro‐inflammatory conformational change in C‐reactive protein

Author

Johannes Zeller, Karen S Cheung Tung Shing, Tracy L Nero, James D McFadyen, Guy Krippner, Balázs Bogner, Sheena Kreuzaler, Jurij Kiefer, Verena K Horner, David Braig, Habiba Danish, Sara Baratchi, Mark Fricke, Xiaowei Wang, Michel G Kather, Bernd Kammerer, Kevin J Woollard, Prerna Sharma, Craig J Morton, Geoffrey Pietersz, Michael W Parker, Karlheinz Peter, and Steffen U Eisenhardt

Subjects
anti‐inflammatory therapy, C‐reactive protein, drug development, ischemia, x‐ray crystallography, reperfusion injury, Medicine (General), R5-920, Genetics, QH426-470
Abstract

Abstract C‐reactive protein (CRP) is an early‐stage acute phase protein and highly upregulated in response to inflammatory reactions. We recently identified a novel mechanism that leads to a conformational change from the native, functionally relatively inert, pentameric CRP (pCRP) structure to a pentameric CRP intermediate (pCRP*) and ultimately to the monomeric CRP (mCRP) form, both exhibiting highly pro‐inflammatory effects. This transition in the inflammatory profile of CRP is mediated by binding of pCRP to activated/damaged cell membranes via exposed phosphocholine lipid head groups. We designed a tool compound as a low molecular weight CRP inhibitor using the structure of phosphocholine as a template. X‐ray crystallography revealed specific binding to the phosphocholine binding pockets of pCRP. We provide in vitro and in vivo proof‐of‐concept data demonstrating that the low molecular weight tool compound inhibits CRP‐driven exacerbation of local inflammatory responses, while potentially preserving pathogen‐defense functions of CRP. The inhibition of the conformational change generating pro‐inflammatory CRP isoforms via phosphocholine‐mimicking compounds represents a promising, potentially broadly applicable anti‐inflammatory therapy.

Published
2023
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