Cell Reports Medicine
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Jul 19, 2022

Volume 3Issue 7
Open Access
On the cover: The US Supreme Court's decision to overturn Roe v. Wade is a setback for medicine and will have a profound effect on perinatal healthcare in the US. In this issue, Megan Allyse and Marsha Michie discuss the consequences of a federal right to abortion on prenatal genetic testing. Cover design by Kristan van der Vos. Image created with Biorender....
On the cover: The US Supreme Court's decision to overturn Roe v. Wade is a setback for medicine and will have a profound effect on perinatal healthcare in the US. In this issue, Megan Allyse and Marsha Michie discuss the consequences of a federal right to abortion on prenatal genetic testing. Cover design by Kristan van der Vos. Image created with Biorender.




  • Prenatal genetics in a post-Roe United States

    • Megan A. Allyse,
    • Marsha Michie
    The Supreme Court removed a federal right to abortion access in June 2022. This returned the legality of abortion to each of the 50 states. This will have a profound impact on the provision of prenatal care in general and prenatal genetic screening and testing.


  • Manipulation of the inflammatory reflex as a therapeutic strategy

    • Mark J. Kelly,
    • Caitríona Breathnach,
    • Kevin J. Tracey,
    • Seamas C. Donnelly
    Increasing evidence has revealed the significant anti-inflammatory activity of the cholinergic pathway. Kelly and colleagues review the current knowledge of the neural inflammatory reflex and highlight recent work harnessing the cholinergic anti-inflammatory pathway as a therapeutic strategy targeting disease.


  • A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions

    • Cynthia M. Estrada-Zuniga,
    • Zi-Ming Cheng,
    • Purushoth Ethiraj,
    • Qianjin Guo,
    • Hector Gonzalez-Cantú,
    • Elaina Adderley,
    • Hector Lopez,
    • Bethany N. Landry,
    • Abir Zainal,
    • Neil Aronin,
    • Yanli Ding,
    • Xiaojing Wang,
    • Ricardo C.T. Aguiar,
    • Patricia L.M. Dahia
    Estrada-Zuniga et al. describe a RET::GRB2 fusion in a pheochromocytoma. In this rearrangement, RET is uniquely positioned upstream to the partner gene GRB2, which encodes a natural RET interacting protein. RET::GRB2 is transforming and sensitive to RET inhibitors, supporting its driver role and highlighting opportunities for targeted therapy in pheochromocytomas.
  • Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant

    • Kirsten E. Lyke,
    • Robert L. Atmar,
    • Clara Dominguez Islas,
    • Christine M. Posavad,
    • Daniel Szydlo,
    • Rahul Paul Chourdhury,
    • Meagan E. Deming,
    • Amanda Eaton,
    • Lisa A. Jackson,
    • Angela R. Branche,
    • Hana M. El Sahly,
    • Christina A. Rostad,
    • Judith M. Martin,
    • Christine Johnston,
    • Richard E. Rupp,
    • Mark J. Mulligan,
    • Rebecca C. Brady,
    • Robert W. Frenck Jr.,
    • Martín Bäcker,
    • Angelica C. Kottkamp,
    • Tara M. Babu,
    • Kumaravel Rajakumar,
    • Srilatha Edupuganti,
    • David Dobrzynski,
    • Rhea N. Coler,
    • Janet I. Archer,
    • Sonja Crandon,
    • Jillian A. Zemanek,
    • Elizabeth R. Brown,
    • Kathleen M. Neuzil,
    • David S. Stephens,
    • Diane J. Post,
    • Seema U. Nayak,
    • Mehul S. Suthar,
    • Paul C. Roberts,
    • John H. Beigel,
    • David C. Montefiori
    • the DMID 21-0012 Study Group
    Following COVID-19 vaccine prime and boost, Lyke et al. find higher Omicron neutralization titers for homologous mRNA boost and heterologous mRNA and Ad26.COV2.S boost compared with homologous Ad26.COV2.S boost. Omicron titers rapidly decline by day 91 compared with prototypic D614G. Moderate differences in neutralization (<3-fold) were noted among Omicron sublineages.
  • Monoclonal antibody treatment drives rapid culture conversion in SARS-CoV-2 infection

    • Julie Boucau,
    • Kara W. Chew,
    • Manish C. Choudhary,
    • Rinki Deo,
    • James Regan,
    • James P. Flynn,
    • Charles R. Crain,
    • Michael D. Hughes,
    • Justin Ritz,
    • Carlee Moser,
    • Joan A. Dragavon,
    • Arzhang C. Javan,
    • Ajay Nirula,
    • Paul Klekotka,
    • Alexander L. Greninger,
    • Robert W. Coombs,
    • William A. Fischer II,
    • Eric S. Daar,
    • David A. Wohl,
    • Joseph J. Eron,
    • Judith S. Currier,
    • Davey M. Smith,
    • the POSITIVES study team,
    • Jonathan Z. Li,
    • Amy K. Barczak
    • the ACTIV-2/A5401 Study Team
    Using longitudinal samples from the ACTIV-2 clinical trial of the monoclonal antibody bamlinivimab, Boucau et al. investigate the duration of shedding culturable virus. Treatment with monoclonal antibody results in rapid clearance of culturable virus. The emergence of mutations in a subset of participants coincides with viral rebound and resurgent culturable virus.


  • Corticostriatal circuits in the transition to chronic back pain: The predictive role of reward learning

    • Martin Löffler,
    • Seth M. Levine,
    • Katrin Usai,
    • Simon Desch,
    • Mina Kandić,
    • Frauke Nees,
    • Herta Flor
    Corticostriatal pathways contribute to the development of chronic back pain. In this issue of Cell Reports Medicine, Löffler et al. demonstrate that reward-learning signals in a prefrontal-limbic pathway predict the transition from subacute to chronic back pain and characterize the chronic stage of back pain.
  • Plaque characteristics and biomarkers predicting regression and progression of carotid atherosclerosis

    • Faisel Khan,
    • Isabel Gonçalves,
    • Angela C. Shore,
    • Andrea Natali,
    • Carlo Palombo,
    • Helen M. Colhoun,
    • Gerd Östling,
    • Francesco Casanova,
    • Cecilia Kennbäck,
    • Kunihiko Aizawa,
    • Margaretha Persson,
    • Kim M. Gooding,
    • David Strain,
    • Helen Looker,
    • Fiona Dove,
    • Jill Belch,
    • Silvia Pinnola,
    • Elena Venturi,
    • Michaela Kozakova,
    • Jan Nilsson
    In a cohort with high-risk subjects, Khan et al. show that progression of atherosclerosis is associated with presence of more fibrotic plaques and higher circulating levels of pro-fibrotic growth factors. Regression of atherosclerosis is more common in subjects with large, less fibrotic plaques and is associated with signs of inflammation.
  • Anlotinib combined with TQB2450 in patients with platinum-resistant or -refractory ovarian cancer: A multi-center, single-arm, phase 1b trial

    • Chun-Yan Lan,
    • Jing Zhao,
    • Fan Yang,
    • Ying Xiong,
    • Rong Li,
    • Yu Huang,
    • Jing Wang,
    • Chang Liu,
    • Xue-Han Bi,
    • Hai-Hong Jin,
    • Jin Meng,
    • Wei-Hong Zhao,
    • Li Zhang,
    • Ya-Fei Wang,
    • Min Zheng,
    • Xin Huang
    Lan et al. demonstrate the efficacy, safety, and survival of anlotinib plus a PD-L1 inhibitor TQB2450 in platinum-resistant or -refractory ovarian cancer. They analyze the association between PD-L1 expression and clinical efficacy. They provide a combination regimen of anti-angiogenic agent and immune checkpoint inhibitor in the platinum-resistant and -refractory setting.
  • Clinical, phenotypic and genetic landscape of case reports with genetically proven inherited disorders of vitamin B12 metabolism: A meta-analysis

    • Arnaud Wiedemann,
    • Abderrahim Oussalah,
    • Nathalie Lamireau,
    • Maurane Théron,
    • Melissa Julien,
    • Jean-Philippe Mergnac,
    • Baptiste Augay,
    • Pauline Deniaud,
    • Tom Alix,
    • Marine Frayssinoux,
    • François Feillet,
    • Jean-Louis Guéant
    This systematic review by Wiedemann et al. highlights age categories and gene clusters as major determinants of patients’ phenotypic landscape in inherited disorders of vitamin B12 metabolism. The diagnosis and management of these disorders must be considered in adult patients who present with neurological and thromboembolic manifestations of unknown origin.
  • Radiogenomic analysis reveals tumor heterogeneity of triple-negative breast cancer

    • Lin Jiang,
    • Chao You,
    • Yi Xiao,
    • He Wang,
    • Guan-Hua Su,
    • Bing-Qing Xia,
    • Ren-Cheng Zheng,
    • Dan-Dan Zhang,
    • Yi-Zhou Jiang,
    • Ya-Jia Gu,
    • Zhi-Ming Shao
    Jiang et al. investigate radiomics as a non-invasive approach for evaluating tumor heterogeneity in triple-negative breast cancer (TNBC). Their study utilizes radiomic features to distinguish the intertumoral heterogeneity of TNBC and identify a prognostic radiomic feature reflecting peritumoral heterogeneity to correlate with immune suppression and metabolic reprogramming in TNBC.
  • Persistence of MERS-CoV-spike-specific B cells and antibodies after late third immunization with the MVA-MERS-S vaccine

    • Leonie M. Weskamm,
    • Anahita Fathi,
    • Matthijs P. Raadsen,
    • Anna Z. Mykytyn,
    • Till Koch,
    • Michael Spohn,
    • Monika Friedrich,
    • MVA-MERS-S Study Group,
    • Bart L. Haagmans,
    • Stephan Becker,
    • Gerd Sutter,
    • Christine Dahlke,
    • Marylyn M. Addo
    Weskamm et al. longitudinally describe B and T cell responses as well as antibody subclasses and neutralization capacity induced by three homologous immunizations with the MVA-MERS-S vaccine candidate. A late booster vaccination significantly enhances the frequency and persistence of memory B cells, binding IgG1 and neutralizing antibodies.
  • Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19

    • Dorien Feyaerts,
    • Julien Hédou,
    • Joshua Gillard,
    • Han Chen,
    • Eileen S. Tsai,
    • Laura S. Peterson,
    • Kazuo Ando,
    • Monali Manohar,
    • Evan Do,
    • Gopal K.R. Dhondalay,
    • Jessica Fitzpatrick,
    • Maja Artandi,
    • Iris Chang,
    • Theo T. Snow,
    • R. Sharon Chinthrajah,
    • Christopher M. Warren,
    • Richard Wittman,
    • Justin G. Meyerowitz,
    • Edward A. Ganio,
    • Ina A. Stelzer,
    • Xiaoyuan Han,
    • Franck Verdonk,
    • Dyani K. Gaudillière,
    • Nilanjan Mukherjee,
    • Amy S. Tsai,
    • Kristen K. Rumer,
    • Danielle R. Jacobsen,
    • Zachary B. Bjornson-Hooper,
    • Sizun Jiang,
    • Sergio Fragoso Saavedra,
    • Sergio Iván Valdés Ferrer,
    • J. Daniel Kelly,
    • David Furman,
    • Nima Aghaeepour,
    • Martin S. Angst,
    • Scott D. Boyd,
    • Benjamin A. Pinsky,
    • Garry P. Nolan,
    • Kari C. Nadeau,
    • Brice Gaudillière,
    • David R. McIlwain
    Feyaerts et al. integrate plasma and single-cell proteomic analysis of patients with mild, moderate, and severe COVID-19 to reveal biological signatures that differentiate COVID-19 severity, including dysregulation of pro-inflammatory signaling networks.
  • Mucosal chemokine adjuvant enhances synDNA vaccine-mediated responses to SARS-CoV-2 and provides heterologous protection in vivo

    • Ebony N. Gary,
    • Nicholas J. Tursi,
    • Bryce Warner,
    • Elizabeth M. Parzych,
    • Ali R. Ali,
    • Drew Frase,
    • Estella Moffat,
    • Carissa Embury-Hyatt,
    • Trevor R.F. Smith,
    • Kate E. Broderick,
    • Laurent Humeau,
    • Darwyn Kobasa,
    • Ami Patel,
    • Daniel W. Kulp,
    • David B. Weiner
    Gary et al. describe how co-immunization with a spike protein DNA vaccine and the mucosal-homing chemokine CCL27 enhances SARS-CoV-2 vaccine-induced responses in the respiratory and gastrointestinal mucosae and supports protection from the SARS-CoV-2 Delta variant. These studies suggest that mucosal targeting may play an important role in broadening vaccine-induced protection against SARS-CoV-2.