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1. Dissection of transcriptome dysregulation and immune characterization in women with germline BRCA1 mutation at single-cell resolution

Author

Xuexin Yu, Wanrun Lin, Alexandra Spirtos, Yan Wang, Hao Chen, Jianfeng Ye, Jessica Parker, Ci Ci Liu, Yiying Wang, Gabriella Quinn, Feng Zhou, Setsuko K. Chambers, Cheryl Lewis, Jayanthi Lea, Bo Li, and Wenxin Zheng

Subjects
High-grade serous carcinoma, Ovarian cancer, BRCA1 mutation, Fallopian tube, Single-cell RNA sequencing, T cell exhaustion, Medicine
Abstract

Abstract Background High-grade serous carcinoma (HGSC) is the most frequent and lethal type of ovarian cancer. It has been proposed that tubal secretory cells are the origin of ovarian HGSC in women with familial BRCA1/2 mutations. However, the molecular changes underlying malignant transformation remain unknown. Method We performed single-cell RNA and T cell receptor sequencing of tubal fimbriated ends from 3 BRCA1 germline mutation carriers (BRCA1 carriers) and 3 normal controls with no high-risk history (non-BRCA1 carriers). Results Exploring the transcriptomes of 19,008 cells, predominantly from BRCA1 + samples, we identified 5 major cell populations in the fallopian tubal mucosae. The secretory cells of BRCA1 + samples had differentially expressed genes involved in tumor growth and regulation, chemokine signaling, and antigen presentation compared to the wild-type BRCA1 controls. There are several novel findings in this study. First, a subset of the fallopian tubal secretory cells from one BRCA1 carrier exhibited an epithelial-to-mesenchymal transition (EMT) phenotype, which was also present in the mucosal fibroblasts. Second, we identified a previously unreported phenotypic split of the EMT secretory cells with distinct evolutionary endpoints. Third, we observed increased clonal expansion among the CD8+ T cell population from BRCA1 + carriers. Among those clonally expanded CD8+ T cells, PD-1 was significantly increased in tubal mucosae of BRCA1 + patients compared with that of normal controls, indicating that T cell exhaustion may occur before the development of any premalignant or malignant lesions. Conclusion These results indicate that EMT and immune evasion in normal-looking tubal mucosae may represent early events leading to the development of HGSC in women with BRCA1 germline mutation. Our findings provide a probable molecular mechanism explaining why some, but not all, women with BRCA1 germline mutation present with early development and rapid dissemination of HGSC.

Published
2022
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2. Mobile health interventions for HIV/STI prevention among youth in low- and middle-income countries (LMICs): a systematic review of studies reporting implementation outcomes

Author

Ucheoma Nwaozuru, Chisom Obiezu-Umeh, Thembekile Shato, Florida Uzoaru, Stacey Mason, Victoria Carter, Sunita Manu, Karan Modi, Jessica Parker, Oliver Ezechi, and Juliet Iwelunmor

Subjects
Mobile health, Young people, HIV/STI prevention, Implementation outcomes, Mobile phone, Low- and middle-income countries, Medicine (General), R5-920
Abstract

Abstract Background Advances and proliferation of technologies such as mobile phones may provide opportunities to improve access to HIV/STI services and reach young people with high risk for HIV and STI. However, the reach, uptake, and sustainability of mobile health (mHealth) HIV/STI interventions targeting young people aged 10–24 years in low- and middle-income countries (LMICs) are largely unknown. To address this gap and to inform implementation science research, a review was conducted to summarize what is known, and what we need to know about implementing mhealth interventions for HIV/STI prevention targeting young people in LMICs. Methods We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for this review. Drawing upon Proctor’s eight implementation outcome measures, we evaluated the acceptability, adoption, appropriateness, cost, feasibility, fidelity, penetration, and sustainability of m-health HIV/STI interventions targeting young people in LMICs. The search was performed from September 2020–January 2021 and updated on March 1, 2021, in Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, SCOPUS, Global Health, and Web of Science. Eligible studies were required to include an HIV/STI prevention outcome, target young people aged 10–24 years, include a comparison/control group, and reporting of atleast one implementation outcome as outlined by Proctor. Results A total of 1386 articles were located, and their titles and abstracts were screened. Of these, 57 full-text articles were reviewed and subsequently, and 11 articles representing 6 unique interventions were included in the systematic review. Acceptability 6 (100%), appropriateness 6 (100%), and feasibility 5(83%) were the most frequently evaluated implementation outcomes. Adoption 2 (33%), fidelity 1 (17%), and cost 1 (17%) were rarely reported; penetration and sustainability were not reported. Conclusions This review contributes to implementation science literature by synthesizing key implementation outcomes of mHealth HIV/STI interventions targeting young people in LMICs. Future research is needed on m-health HIV/STI implementation outcomes, particularly the penetration, cost, and long-term sustainability of these interventions. Doing so will enhance the field’s understanding of the mechanisms by which these interventions lead or do not lead to changes in high HIV/STI risk and vulnerability among young people in LMICs.

Published
2021
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3. Development and validation of behavioral intention measures of an E-vapor product: intention to try, use, dual use, and switch

Author

Stacey A. McCaffrey, Jessica Parker Zdinak, Stephanie Plunkett, Elizabeth Becker, Jennifer N. Lewis, and Ryan A. Black

Subjects
Behavioral intention, Psychometric validation, Rasch model, E-vapor, Intention to switch, Public health, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background The harm caused by tobacco use is primarily attributable to cigarette smoking. Switching completely to non-combustible products may reduce disease risks in adult cigarette smokers who are unable or unwilling to quit. Before a new tobacco product can enter the market or can be marketed as a modified risk tobacco product, the manufacturer must determine the impact that the product will have on the likelihood of changes in tobacco use behavior among both tobacco users and nonusers. One way to estimate change in tobacco use behavior is to assess tobacco users’ and nonusers’ behavioral intentions toward the product and its marketing, including intentions to try, use, dual use, and switch to the product from cigarettes. The purpose of this study was to develop and validate behavioral intention metrics appropriate for use with current, former, and never adult tobacco users. Methods Preliminary items were subjected to cognitive testing with adult (1) smokers planning to quit cigarettes in the next 30 days, (2) smokers not planning to quit cigarettes in the next 30 days, (3) e-vapor users, (4) former tobacco users, and (5) never tobacco users. Items were iteratively revised based on feedback during cognitive testing, and surviving items were administered to a large sample of adults (N = 2943) representing the aforementioned sub-groups. Rating scale functioning, reliability, validity, bias, and ability to detect change were evaluated. Results Examination of the response category thresholds generated by the Rasch model provided evidence that the rating scales were functioning appropriately. Results revealed good stability and excellent internal consistency and person reliability and provided evidence of unidimensionality and convergent validity. Estimates of reliability and validity were similar across sub-groups. A cross-validation sample generally confirmed findings from the validation sample. No items were discarded due to differential item function. Exploratory analyses provided support for ability to detect change. Conclusions Results from this rigorous, empirical evaluation using large validation and cross-validation samples provide strong support for the psychometric properties of the Intention to Try, Use, Dual Use, and Switch scales with current, former, and never adult tobacco users.

Published
2021
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4. 26th Annual Computational Neuroscience Meeting (CNS*2017): Part 2

Author

Leonid L. Rubchinsky, Sungwoo Ahn, Wouter Klijn, Ben Cumming, Stuart Yates, Vasileios Karakasis, Alexander Peyser, Marmaduke Woodman, Sandra Diaz-Pier, James Deraeve, Eliana Vassena, William Alexander, David Beeman, Pawel Kudela, Dana Boatman-Reich, William S. Anderson, Niceto R. Luque, Francisco Naveros, Richard R. Carrillo, Eduardo Ros, Angelo Arleo, Jacob Huth, Koki Ichinose, Jihoon Park, Yuji Kawai, Junichi Suzuki, Hiroki Mori, Minoru Asada, Sorinel A. Oprisan, Austin I. Dave, Tahereh Babaie, Peter Robinson, Alejandro Tabas, Martin Andermann, André Rupp, Emili Balaguer-Ballester, Henrik Lindén, Rasmus K. Christensen, Mari Nakamura, Tania R. Barkat, Zach Tosi, John Beggs, Davide Lonardoni, Fabio Boi, Stefano Di Marco, Alessandro Maccione, Luca Berdondini, Joanna Jędrzejewska-Szmek, Daniel B. Dorman, Kim T. Blackwell, Christoph Bauermeister, Hanna Keren, Jochen Braun, João V. Dornas, Eirini Mavritsaki, Silvio Aldrovandi, Emma Bridger, Sukbin Lim, Nicolas Brunel, Anatoly Buchin, Clifford Charles Kerr, Anton Chizhov, Gilles Huberfeld, Richard Miles, Boris Gutkin, Martin J. Spencer, Hamish Meffin, David B. Grayden, Anthony N. Burkitt, Catherine E. Davey, Liangyu Tao, Vineet Tiruvadi, Rehman Ali, Helen Mayberg, Robert Butera, Cengiz Gunay, Damon Lamb, Ronald L. Calabrese, Anca Doloc-Mihu, Víctor J. López-Madrona, Fernanda S. Matias, Ernesto Pereda, Claudio R. Mirasso, Santiago Canals, Alice Geminiani, Alessandra Pedrocchi, Egidio D’Angelo, Claudia Casellato, Ankur Chauhan, Karthik Soman, V. Srinivasa Chakravarthy, Vignayanandam R. Muddapu, Chao-Chun Chuang, Nan-yow Chen, Mehdi Bayati, Jan Melchior, Laurenz Wiskott, Amir Hossein Azizi, Kamran Diba, Sen Cheng, Elena Y. Smirnova, Elena G. Yakimova, Anton V. Chizhov, Nan-Yow Chen, Chi-Tin Shih, Dorian Florescu, Daniel Coca, Julie Courtiol, Viktor K. Jirsa, Roberto J. M. Covolan, Bartosz Teleńczuk, Richard Kempter, Gabriel Curio, Alain Destexhe, Jessica Parker, Alexander N. Klishko, Boris I. Prilutsky, Gennady Cymbalyuk, Felix Franke, Andreas Hierlemann, Rava Azeredo da Silveira, Stefano Casali, Stefano Masoli, Martina Rizza, Martina Francesca Rizza, Yinming Sun, Willy Wong, Faranak Farzan, Daniel M. Blumberger, Zafiris J. Daskalakis, Svitlana Popovych, Shivakumar Viswanathan, Nils Rosjat, Christian Grefkes, Silvia Daun, Damiano Gentiletti, Piotr Suffczynski, Vadym Gnatkovski, Marco De Curtis, Hyeonsu Lee, Se-Bum Paik, Woochul Choi, Jaeson Jang, Youngjin Park, Jun Ho Song, Min Song, Vicente Pallarés, Matthieu Gilson, Simone Kühn, Andrea Insabato, Gustavo Deco, Katharina Glomb, Adrián Ponce-Alvarez, Petra Ritter, Adria Tauste Campo, Alexander Thiele, Farah Deeba, P. A. Robinson, Sacha J. van Albada, Andrew Rowley, Michael Hopkins, Maximilian Schmidt, Alan B. Stokes, David R. Lester, Steve Furber, Markus Diesmann, Alessandro Barri, Martin T. Wiechert, David A. DiGregorio, Alexander G. Dimitrov, Catalina Vich, Rune W. Berg, Antoni Guillamon, Susanne Ditlevsen, Romain D. Cazé, Benoît Girard, Stéphane Doncieux, Nicolas Doyon, Frank Boahen, Patrick Desrosiers, Edward Laurence, Louis J. Dubé, Russo Eleonora, Daniel Durstewitz, Dominik Schmidt, Tuomo Mäki-Marttunen, Florian Krull, Francesco Bettella, Christoph Metzner, Anna Devor, Srdjan Djurovic, Anders M. Dale, Ole A. Andreassen, Gaute T. Einevoll, Solveig Næss, Torbjørn V. Ness, Geir Halnes, Eric Halgren, Klas H. Pettersen, Marte J. Sætra, Espen Hagen, Alina Schiffer, Axel Grzymisch, Malte Persike, Udo Ernst, Daniel Harnack, Udo A. Ernst, Nergis Tomen, Stefano Zucca, Valentina Pasquale, Giuseppe Pica, Manuel Molano-Mazón, Michela Chiappalone, Stefano Panzeri, Tommaso Fellin, Kelvin S. Oie, David L. Boothe, Joshua C. Crone, Alfred B. Yu, Melvin A. Felton, Isma Zulfiqar, Michelle Moerel, Peter De Weerd, Elia Formisano, Kelvin Oie, Piotr Franaszczuk, Roland Diggelmann, Michele Fiscella, Domenico Guarino, Jan Antolík, Andrew P. Davison, Yves Frègnac, Benjamin Xavier Etienne, Flavio Frohlich, Jérémie Lefebvre, Encarni Marcos, Maurizio Mattia, Aldo Genovesio, Leonid A. Fedorov, Tjeerd M.H. Dijkstra, Louisa Sting, Howard Hock, Martin A. Giese, Laure Buhry, Clément Langlet, Francesco Giovannini, Christophe Verbist, Stefano Salvadé, Michele Giugliano, James A. Henderson, Hendrik Wernecke, Bulcsú Sándor, Claudius Gros, Nicole Voges, Paulina Dabrovska, Alexa Riehle, Thomas Brochier, Sonja Grün, Yifan Gu, Pulin Gong, Grégory Dumont, Nikita A. Novikov, Boris S. Gutkin, Parul Tewatia, Olivia Eriksson, Andrei Kramer, Joao Santos, Alexandra Jauhiainen, Jeanette H. Kotaleski, Jovana J. Belić, Arvind Kumar, Jeanette Hellgren Kotaleski, Masanori Shimono, Naomichi Hatano, Subutai Ahmad, Yuwei Cui, Jeff Hawkins, Johanna Senk, Karolína Korvasová, Tom Tetzlaff, Moritz Helias, Tobias Kühn, Michael Denker, PierGianLuca Mana, David Dahmen, Jannis Schuecker, Sven Goedeke, Christian Keup, Katja Heuer, Rembrandt Bakker, Paul Tiesinga, Roberto Toro, Wei Qin, Alex Hadjinicolaou, Michael R. Ibbotson, Tatiana Kameneva, William W. Lytton, Lealem Mulugeta, Andrew Drach, Jerry G. Myers, Marc Horner, Rajanikanth Vadigepalli, Tina Morrison, Marlei Walton, Martin Steele, C. Anthony Hunt, Nicoladie Tam, Rodrigo Amaducci, Carlos Muñiz, Manuel Reyes-Sánchez, Francisco B. Rodríguez, Pablo Varona, Joseph T. Cronin, Matthias H. Hennig, Elisabetta Iavarone, Jane Yi, Ying Shi, Bas-Jan Zandt, Werner Van Geit, Christian Rössert, Henry Markram, Sean Hill, Christian O’Reilly, Rodrigo Perin, Huanxiang Lu, Alexander Bryson, Michal Hadrava, Jaroslav Hlinka, Ryosuke Hosaka, Mark Olenik, Conor Houghton, Nicolangelo Iannella, Thomas Launey, Rebecca Kotsakidis, Jaymar Soriano, Takatomi Kubo, Takao Inoue, Hiroyuki Kida, Toshitaka Yamakawa, Michiyasu Suzuki, Kazushi Ikeda, Samira Abbasi, Amber E. Hudson, Detlef H. Heck, Dieter Jaeger, Joel Lee, Skirmantas Janušonis, Maria Luisa Saggio, Andreas Spiegler, William C. Stacey, Christophe Bernard, Davide Lillo, Spase Petkoski, Mark Drakesmith, Derek K. Jones, Ali Sadegh Zadeh, Chandra Kambhampati, Jan Karbowski, Zeynep Gokcen Kaya, Yair Lakretz, Alessandro Treves, Lily W. Li, Joseph Lizier, Cliff C. Kerr, Timothée Masquelier, Saeed Reza Kheradpisheh, Hojeong Kim, Chang Sub Kim, Julia A. Marakshina, Alexander V. Vartanov, Anastasia A. Neklyudova, Stanislav A. Kozlovskiy, Andrey A. Kiselnikov, Kanako Taniguchi, Katsunori Kitano, Oliver Schmitt, Felix Lessmann, Sebastian Schwanke, Peter Eipert, Jennifer Meinhardt, Julia Beier, Kanar Kadir, Adrian Karnitzki, Linda Sellner, Ann-Christin Klünker, Lena Kuch, Frauke Ruß, Jörg Jenssen, Andreas Wree, Paula Sanz-Leon, Stuart A. Knock, Shih-Cheng Chien, Burkhard Maess, Thomas R. Knösche, Charles C. Cohen, Marko A. Popovic, Jan Klooster, Maarten H.P. Kole, Erik A. Roberts, Nancy J. Kopell, Daniel Kepple, Hamza Giaffar, Dima Rinberg, Alex Koulakov, Caroline Garcia Forlim, Leonie Klock, Johanna Bächle, Laura Stoll, Patrick Giemsa, Marie Fuchs, Nikola Schoofs, Christiane Montag, Jürgen Gallinat, Ray X. Lee, Greg J. Stephens, Bernd Kuhn, Luiz Tauffer, Philippe Isope, Katsuma Inoue, Yoshiyuki Ohmura, Shogo Yonekura, Yasuo Kuniyoshi, Hyun Jae Jang, Jeehyun Kwag, Marc de Kamps, Yi Ming Lai, Filipa dos Santos, K. P. Lam, Peter Andras, Julia Imperatore, Jessica Helms, Tamas Tompa, Antonieta Lavin, Felicity H. Inkpen, Michael C. Ashby, Nathan F. Lepora, Aaron R. Shifman, John E. Lewis, Zhong Zhang, Yeqian Feng, Christian Tetzlaff, Tomas Kulvicius, Yinyun Li, Rodrigo F. O. Pena, Davide Bernardi, Antonio C. Roque, Benjamin Lindner, Sebastian Vellmer, Ausra Saudargiene, Tiina Maninen, Riikka Havela, Marja-Leena Linne, Arthur Powanwe, Andre Longtin, Jesús A. Garrido, Joe W. Graham, Salvador Dura-Bernal, Sergio L. Angulo, Samuel A. Neymotin, and Srdjan D. Antic

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Published
2017
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5. Mobile health interventions for HIV/STI prevention among youth in low- and middle-income countries (LMICs): a systematic review of studies reporting implementation outcomes

Author

Victoria Carter, Ucheoma Nwaozuru, Oliver Ezechi, Stacey Mason, Chisom Obiezu-Umeh, Sunita Manu, Karan Modi, Thembekile Shato, Juliet Iwelunmor, Florida Uzoaru, and Jessica Parker

Subjects
medicine.medical_specialty, Medicine (General), Low- and middle-income countries, business.industry, HIV/STI prevention, Public health, Implementation outcomes, Psychological intervention, Health services research, General Medicine, CINAHL, Health administration, Systematic review, R5-920, Family medicine, medicine, Young people, Systematic Review, Mobile health, business, mHealth, Mobile phone, Health policy
Abstract

Background Advances and proliferation of technologies such as mobile phones may provide opportunities to improve access to HIV/STI services and reach young people with high risk for HIV and STI. However, the reach, uptake, and sustainability of mobile health (mHealth) HIV/STI interventions targeting young people aged 10–24 years in low- and middle-income countries (LMICs) are largely unknown. To address this gap and to inform implementation science research, a review was conducted to summarize what is known, and what we need to know about implementing mhealth interventions for HIV/STI prevention targeting young people in LMICs. Methods We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for this review. Drawing upon Proctor’s eight implementation outcome measures, we evaluated the acceptability, adoption, appropriateness, cost, feasibility, fidelity, penetration, and sustainability of m-health HIV/STI interventions targeting young people in LMICs. The search was performed from September 2020–January 2021 and updated on March 1, 2021, in Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, SCOPUS, Global Health, and Web of Science. Eligible studies were required to include an HIV/STI prevention outcome, target young people aged 10–24 years, include a comparison/control group, and reporting of atleast one implementation outcome as outlined by Proctor. Results A total of 1386 articles were located, and their titles and abstracts were screened. Of these, 57 full-text articles were reviewed and subsequently, and 11 articles representing 6 unique interventions were included in the systematic review. Acceptability 6 (100%), appropriateness 6 (100%), and feasibility 5(83%) were the most frequently evaluated implementation outcomes. Adoption 2 (33%), fidelity 1 (17%), and cost 1 (17%) were rarely reported; penetration and sustainability were not reported. Conclusions This review contributes to implementation science literature by synthesizing key implementation outcomes of mHealth HIV/STI interventions targeting young people in LMICs. Future research is needed on m-health HIV/STI implementation outcomes, particularly the penetration, cost, and long-term sustainability of these interventions. Doing so will enhance the field’s understanding of the mechanisms by which these interventions lead or do not lead to changes in high HIV/STI risk and vulnerability among young people in LMICs.

Published
2021

6. Development and validation of behavioral intention measures of an E-vapor product: intention to try, use, dual use, and switch

Author

Ryan A. Black, Stacey A. McCaffrey, Jessica Parker Zdinak, Jennifer N. Lewis, Stephanie Plunkett, and Elizabeth Becker

Subjects
Adult, Male, E-vapor, Adolescent, Psychometrics, Applied psychology, Computer applications to medicine. Medical informatics, R858-859.7, Sample (statistics), Intention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Rating scale, Humans, 030212 general & internal medicine, Product (category theory), Behavioral intention, Psychometric validation, Reliability (statistics), Aged, Aged, 80 and over, Public health, Smokers, 030505 public health, Rasch model, Research, Vaping, Smoking, Public Health, Environmental and Occupational Health, Reproducibility of Results, General Medicine, Middle Aged, Intention to switch, Cognitive test, Convergent validity, Female, 0305 other medical science, Psychology, Risk Reduction Behavior
Abstract

Background The harm caused by tobacco use is primarily attributable to cigarette smoking. Switching completely to non-combustible products may reduce disease risks in adult cigarette smokers who are unable or unwilling to quit. Before a new tobacco product can enter the market or can be marketed as a modified risk tobacco product, the manufacturer must determine the impact that the product will have on the likelihood of changes in tobacco use behavior among both tobacco users and nonusers. One way to estimate change in tobacco use behavior is to assess tobacco users’ and nonusers’ behavioral intentions toward the product and its marketing, including intentions to try, use, dual use, and switch to the product from cigarettes. The purpose of this study was to develop and validate behavioral intention metrics appropriate for use with current, former, and never adult tobacco users. Methods Preliminary items were subjected to cognitive testing with adult (1) smokers planning to quit cigarettes in the next 30 days, (2) smokers not planning to quit cigarettes in the next 30 days, (3) e-vapor users, (4) former tobacco users, and (5) never tobacco users. Items were iteratively revised based on feedback during cognitive testing, and surviving items were administered to a large sample of adults (N = 2943) representing the aforementioned sub-groups. Rating scale functioning, reliability, validity, bias, and ability to detect change were evaluated. Results Examination of the response category thresholds generated by the Rasch model provided evidence that the rating scales were functioning appropriately. Results revealed good stability and excellent internal consistency and person reliability and provided evidence of unidimensionality and convergent validity. Estimates of reliability and validity were similar across sub-groups. A cross-validation sample generally confirmed findings from the validation sample. No items were discarded due to differential item function. Exploratory analyses provided support for ability to detect change. Conclusions Results from this rigorous, empirical evaluation using large validation and cross-validation samples provide strong support for the psychometric properties of the Intention to Try, Use, Dual Use, and Switch scales with current, former, and never adult tobacco users.

Published
2021

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