tbuckley/cabot-search huggingface dataset:
Analysis of the Different Surveillance Strategies for Patients with Hodgkin Lymphoma in Clinical Remission after First-Line Treatment. a Study of the Geltamo Group (Spanish lymphoma and autologous transplant group)
Authors: Mariana Bastos-Oreiro, Nieves Lopez, Pilar Gomez, Liébana Marta, Laura LLorente, Antonio Gutiérrez, EVA Domingo Domenech, Maria Jesus Vidal Maceñido, Raquel Del Campo, Leyre Bento, Daniel Garcia, Miriam Santero, Jaime Perez De Oteyza, Belén Navarro, Antonia Rodriguez Izquierdo, Ramón García-Sanz
Journal: Blood (2019)
Tuberculosis in Deer Hunters
Authors: Bridget Kuehn
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Thromboxane Receptor Activates the AMP-Activated Protein Kinase in Vascular Smooth Muscle Cells via Hydrogen Peroxide
Authors: MiaoZhang, YunzhouDong, JianXu, ZhonglinXie, YongWu, PingSong, MelissaGuzman, JiliangWu, Ming-HuiZou
Journal: Circulation Research (2008)

Thromboxane A2 receptor (TPr) stimulation induces cellular hypertrophy in vascular smooth muscle cells (VSMCs); however, regulation of VSMC hypertrophy remains poorly understood. Here we show that TPr stimulation activates AMP-activated kinase (AMPK), which in turn limits TPr-induced protein synthesis in VSMCs. Exposure of cultured VSMCs to either TPr agonists, IBOP and U46619, or exogenous hydrogen peroxide (H2O2) caused time- and dose-dependent AMPK activation, as evidenced by increased phosphorylation of both AMPK-Thr172 and acetyl-coenzyme A carboxylase–Ser79, a downstream enzyme of AMPK, whereas SQ29548, a selective TPr antagonist, significantly attenuated TPr-enhanced AMPK activation. In parallel, both IBOP and U46619 significantly increased the production of reactive oxygen species such as H2O2. Furthermore, adenoviral overexpression of catalase (an H2O2 scavenger) abolished, whereas superoxide dismutase (which catalyzes H2O2 formation) enhanced, IBOP-induced AMPK activation, suggesting that TPr-ac...
PATH-54. MULTI-DIMENSIONAL MOLECULAR CHARACTERIZATION OF PATIENT-MATCHED MEDULLOBLASTOMA AT DIAGNOSIS AND RELAPSE
Authors: Rahul Kumar, Maximilian Deng, Kyle Smith, Anthony P Y Liu, Vasilisa Rudneva, Girish Dhall, Laura Kleese, Daniel Bowers, Murali Chintagumpala, Sarah Leary, Javad Nazarian, Brent Orr, Giles Robinson, Stefan Pfister, Andrey Korshunov, Amar Gajjar, David Jones, Paul Northcott
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Recurrent medulloblastoma (MB) confers an abysmal prognosis with ~10% 5-year overall survival. Optimal treatment paradigms for relapsed disease are largely unknown. Conservation of molecular subgroup at relapse has been described and divergent clonal evolution implicated, yet multi-dimensional molecular characterization of larger cohorts are warranted to substantiate these findings and to disclose potential mechanisms underlying treatment failure and disease recurrence. METHODS A multi-institutional series of 85 patient-matched, primary MBs and their relapses was profiled by DNA methylation array (Illumina 450K/850K). Entity and molecular subgroup classifications were assigned using random forest tumor classifiers (Molecular Neuropathology v.11b4). Genome-wide copy-number aberrations were also inferred from these data while parallel next-generation (whole-exome or targeted panel) sequencing on the majority of the cohort facilitated inference of somatic driver mutations. RESULTS Comprised of WNT (1%), SHH (41%), Group 3 (22%), Group 4 (35%), primary tumors largely retained subgroup affiliation at relapse with the notable exception of 14% of cases. The majority (8/12) of discrepant classifications were determined to be secondary glioblastomas, while three Group 4 primary tumors relapsed as Group 3. Amongst conserved pairs, copy-number analyses suggest somatic clonal divergence between primary MBs and their respective relapses with an average of 0.8 (range 0–5) primary-specific and 2.0 (range 0–11) relapse-specific cytogenetic alterations. Despite high global methylation correlations between primary/relapse pairs (median 0.95), epigenetic evolution at relapse is suggested by the lower degree of conservation amongst promoter-associated probes (median 0.83, p &lt; 2.2e-16). CONCLUSION Secondary malignancy, particularly glioblastoma, may masquerade as relapsed MB, highlighting the utility of molecular characterization for relapsed disease and necessity for vigilant clinical surveillance. By deciphering the evolution of MB from diagnosis to relapse, a fundamental understanding of disease pathogenesis may be garnered, motivating rational and targeted clinical interventions in early therapy and at the time of relapse.
SURG-06. FOLLOWING INTRAOPERATIVE TUMOR-FREE PRINCIPLES IS AN EFFECTIVE APPROACH TO IMPROVE SURVIVAL OF PATIENTS WITH GLIOBLASTOMA
Authors: Yonggao Mou, Al-Nahari Fuad, Hao Duan, Zhenqiang He, Guanhua Zhang, Xiangheng Zhang, Ke Sai, Chao Ke, Ji Zhang, Xiaobing Jiang, Fuhua Lin, Zhenghe Chen, Yinsheng Chen
Journal: Neuro-Oncology (2019)

Abstract The intraoperative tumor-free principles refer to the operation techniques that must be carried out to prevent the exfoliation and planting of tumor cells during the operation, so as to prevent local recurrence and distant metastasis. Following the intraoperative tumor-free principles has been valued in resection of extracranial solid tumors. However, the significance of intraoperative tumor-free principles for brain tumors is still unclear. We retrospectively analyzed 106 patients with primary glioblastoma who underwent resection following the intraoperative tumor-free principles from 2010 to 2016. By February 28, 2019, 11 (10.4%) patients were lost to follow-up. The median overall survival (OS) was 20.2 months, and the 1-, 3-, and 5-year survival rates were 71%, 30%, and 26%, respectively. For patients with complete tumor resection, the median OS was 24.8 months, and the 1-, 3-, and 5-year survival rates were 80%, 38%, and 36%, respectively. Patients who received postoperative Stupp regimen had a median OS of 74.1 months, and the 1-, 3-, and 5-year survival rates were 82%, 51%, and 51%, respectively. A total of 36 patients had complete tumor resection followed by Stupp regimen. Their 1-, 3-, and 5-year survival rates were 94%, 68%, and 68%, respectively. Median OS was not reached. The patient with the longest OS had survived for 108 months and was still alive. In summary, the OS of patients in this study was relatively longer than that reported in most previous literatures, which suggests that following the intraoperative tumor-free principles in resection of GBM can benefit patient survival.
Abstract 17184: Nearly One Third of GWAS CAD Are Putative SMC Klf4 or Oct4 Targets in Advanced Atherosclerotic Lesions
Authors: Gabriel F Alencar, Ryan Haskins, Vamsidhar M Venkata, Johan Bjorkegren, Stefan Bekiranov, Gary K Owens
Journal: Circulation (2018)

Atherosclerosis is a disease of chronic inflammation and the leading cause of morbidity and mortality worldwide. Despite decades of research, our understanding of the mechanisms regulating plaque stability remains poor. Until recently, smooth muscle cells (SMCs) were thought to play an athero-protective role in lesion pathogenesis. However, rigorous lineage tracing has shown a significant portion (&amp;gt;80%) of SMC-derived cells within an advanced atherosclerotic lesion did not express detectable SMC markers. Furthermore, SMC-specific conditional KO of Klf4 resulted in reduction of several indices of plaque instability and SMC-derived macrophage-like cells. In contrast, conditional KO of Oct4 in SMCs presented a reduction of SMC and increased of Lgals3+ cells within lesions, as well as increase of several indices of plaque instability. Taken together, SMCs can have a beneficial or detrimental effect in lesion pathogenesis. Hypothesis: Combinatorial analysis of Oct4/Klf4 ChIP-seq and RNA-seq of advanced atherosclerotic lesions from our SMC-Klf4 and SMC-Oct4 mice provide a unique opportunity to identify genes that play a critical role in regulating beneficial or detrimental changes in SMC phenotype. Results: SMC-Oct4 target genes are enriched for migration pathways, while SMC-Klf4 target genes are enriched for inflammation pathways. Further, atherosclerosis pathway, among others, presented significant opposite patterns (SMC-Oct4-KO up-regulation and SMC-Klf4-KO down-regulation), and presented strong significant gene anti-correlation, corroborating our phenotypic observations. Remarkably, we cross-reference our ChIP-seq datasets with CAD GWAS and found that 54 of the 161 human loci were either Klf4 and/or Oct4 SMC targets, highly suggesting that CAD GWAS genes might be affecting SMC function in lesion development/pathogenesis. To validate our results, we used the STARNET dataset, and we observed that both Oct4 and Klf4 are significantly up-regulated in aorta of CAD patients compared to controls. In addition, co-expression analysis shows that one of the Klf4 network is highly related to human GWAS CAD, including genes such as LDLR, APOE, PCSK9, TRIB1, and others. Surprisingly, more than 35% of genes in this network also are present in our SMC Klf4 ChIP-seq dataset. Conclusions: our results suggests that: late stage atherosclerotic lesions of mouse and humans seems to be more similar than previously thought; and nearly 1/3 of CAD GWAS loci appear to be affecting SMC function and are potentially Klf4/Oct4-dependent.
Systematic Investigation of Microenvironmental Drug Resistance Mechanisms in Chronic Lymphocytic Leukemia
Authors: Peter-Martin Bruch, Holly Giles, Carolin Kolb, Sophie Rabe, Tobias Roider, Mareike Knoll, Mark Kriegsmann, Katharina Kriegsmann, Christiane Zgorzelski, Sebastian Scheinost, Lena Wagner, Carsten Müller-Tidow, Thorsten Zenz, Wolfgang Huber, Sascha Dietrich
Journal: Blood (2019)
CBMT-16. EGFRvIII EXPRESSION CONFERS CHEMOSENSITIVITY BY INCREASING DNA MISMATCH REPAIR PROTEIN EXPRESSION AND REPLICATION STRESS
Authors: Nina Struve, Zev A Binder, Lucy F Stead, Tim Brend, Stephen J Bagley, Claire Faulkner, Leonie Ott, Justus Müller-Goebel, Anna-Sophie Weik, Konstantin Hoffer, Thorsten Rieckmann, Ann Christin Parplys, Jasmin Burmester, Marvin Henze, Jennifer J D Morrissette, Ulrich Schüller, Cordula Petersen, Kai Rothkamm, Kathreena M Kurian, Susan C Short, Malte Kriegs
Journal: Neuro-Oncology (2019)

Abstract MGMT promoter methylation is the only accepted biomarker with prognostic role in GBM but its routine implementation is limited partly response to TMZ is heterogeneous, but also due to lack of effective alternative treatment options. Therefore, additional biomarkers are needed to enable better prediction of survival and to improve individualized treatment of GBM patients. A potential new biomarker is the epidermal growth factor receptor variant III (EGFRvIII). This constitutively activated deletion variant is present in approximately one third of all IDH wildtype GBM, but its relevance to treatment response is poorly understood. The aim of the present study was to analyze the impact of endogenous EGFRvIII expression on chemosensitivity and the mechanisms underlying any differential treatment response. EGFRvIII expression was associated with prolonged median overall survival but only for GBM patients with MGMT promoter methylated tumors. In line with this, we observed increased TMZ sensitivity of EGFRvIII+ and MGMT promoter methylated cells, which translated into improved survival in xenograft experiments. The increased TMZ sensitivity was associated with an elevated DNA damage induction accompanied by an increased expression of DNA mismatch repair (MMR) proteins in EGFRvIII+ cell lines and EGFRvIII+ GBM patient samples. Subsequently, only a moderate reduction in MMR protein expression resulted in a dramatic TMZ resistance, suggesting that EGFRvIII expression specifically sensitized MGMT deficient cells to TMZ treatment by upregulating MMR. Furthermore, EGFRvIII expression in GBM cell lines was accompanied by increased DNA damage, replication fork slowing, stalling and enhanced origin firing, implying replication stress. Targeting of EGFRvIII-dependent replication stress by irinotecan led to hypersensitivity of EGFRvIII+ cells. Taken together this study illustrates that EGFRvIII-induced upregulation of MMR and replication stress increases chemosensitivity thereby highlighting the vulnerability of EGFRvIII+ GBM to available treatments. These important data may also guide the development of new and more effective personalized strategies.
Association of Seasonal Severity and Vaccine Effectiveness With Influenza Vaccination Rates in Children
Authors: Claire Abraham, Qixuan Chen, Weijia Fan, Melissa S. Stockwell
Journal: JAMA Pediatrics (2019)

Association of Seasonal Severity and Vaccine Effectiveness With Influenza Vaccination Rates in ChildrenInfluenza vaccination rates among children remain lower than other pediatric and adolescent vaccines. 1,2 Many variables may affect whether a child is vaccinated against influenza. 3However, to what extent, if any, the severity of an influenza season and either current or prior year's vaccine effectiveness (VE) may affect vaccination rates has yet to be studied, to our knowledge.This information may be important in understanding how to message severity and VE data to parents.Therefore, using publicly available data, we examined the associations of seasonal influenza severity as well as current and prior year's VE with yearly vaccination rates within age groups.
International Multi-Site Clinical Validation of Point-of-Care Microchip Electrophoresis Test for Hemoglobin Variant Identification
Authors: Arwa Fraiwan, Muhammad Noman Hasan, Ran An, Julia Z. Xu, Amy J. Rezac, Nicholas J. Kocmich, Tolulope Oginni, Grace Mfon Olanipekun, Fatimah Hassan-Hanga, Binta W. Jibir, Safiya Gambo, Anil K. Verma, Praveen K. Bharti, Suchada Riolueang, Takdanai Ngimhung, Thidarat Suksangpleng, Priyaleela Thota, Rajasubramaniam Shanmugam, Aparup Das, Vip Viprakasit, Connie M. Piccone, Jane A. Little, Stephen K. Obaro, Umut A. Gurkan
Journal: Blood (2019)
The Use of CEP (Lomustine, Etoposide and Prednisone), an All-Oral Palliative Chemotherapy Regimen, in Aggressive Lymphomas
Authors: Lakshman Vasanthamohan, Brent Parker, Joy Mangel, Selay Lam, Kang Howson-Jan, Chai Wye Phua
Journal: Blood (2019)
Adherence to Treatment in Myelofibrosis Patients: Preliminary Results from Italian Romei Observational Study
Authors: Paola Guglielmelli, Francesca Palandri, Carmine Selleri, Daniela Cilloni, Francesco Mendicino, Patrizio Mazza, Domenico Pastore, Giuseppe A. Palumbo, Sergio Siragusa, Vincenzo Pavone, Stefana Impera, Mara Morelli, Francesco Passamonti, Massimo Breccia
Journal: Blood (2019)
Results from the Completed Dose-Escalation of the Hematological Arm of the Phase I Think Study Evaluating Multiple Infusions of NKG2D-Based CAR T-Cells As Standalone Therapy in Relapse/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients
Authors: David A Sallman, Jason B. Brayer, Xavier Poire, Violaine Havelange, Ahmad Awada, Philippe Lewalle, Kunle Odunsi, Eunice S. Wang, Caroline Lonez, Thomas Lequertier, Erik Alcantar-Orozco, Nathalie Braun, Anne Flament, Ine Moors, Tessa Kerre
Journal: Blood (2019)
CBMT-30. TARGETING NICOTINAMIDE ADENINE DINUCLEOTIDE BIOSYNTHESIS IN CNS TUMORS
Authors: Ken Lindsay, Charles Brenner, David Hockenbery, Patrick Paddison
Journal: Neuro-Oncology (2019)

Abstract Nicotinamide adenine dinucleotide (NAD) metabolic pathways have been shown to be critical targets in many cancers, including brain tumors. However, inhibiting nicotinamide metabolism has had limited efficacy in the clinic to date due to on-target side effects. To identify new metabolic vulnerabilities in human Glioblastoma, we performed a chemical library screen using 250 inhibitors of metabolic enzymes in Glioblastoma stem-like cells (GSCs) (0131 and 0827) and control hNPC-CB660 cells. Among the screen hits, we identified FK866, an inhibitor of the NAD salvage enzyme NAMPT, as having GSC-selective cytotoxicity. Taking an advantage of an alternative NAD precursor salvage pathway, we show that cytotoxicity with inhibitors of the NAMPT salvage enzyme for neural stem cells was abrogated by media addition of nicotinamide riboside (NR), while certain glioblastoma stem-like cells (GSCs) remained exquisitely sensitive. Examining our GSC isolates, we observed that hypersensitivity correlated with low/absent expression of NMRK1, a kinase required for utilization of NR. We find that 5–20% of most tumor types (CNS, non-CNS) exhibit comparably low NMRK1 mRNA expression. In looking for associations with oncogenic drivers, we noted significant negative correlation with MYCN and MYC expression for multiple tumors. We have additional data suggesting that MYC/MYCN induces the NMRK1low state via transcriptional repression. These results suggest that NAMPT inhibitors, already in clinical trials, can be administered with NR to widen the therapeutic index for NMRK1low tumors. This combined theranostic approach could protect NMRK1-proficient normal cells without compromising treatment efficacy in NMRK1low tumor cells.
Eltrombopag Following Chemotherapy and G-CSF+/- Plerixafor for Mobilization and Collection of Hematopoietic Progenitor Cells (HPC) in Lymphoma and Myeloma Patients
Authors: Krishna Joshi, Appalanaidu Sasapu, Muthu Veeraputhiran, Frits van Rhee, Maurizio Zangari, Michele H Cottler-Fox
Journal: Blood (2019)
Varicose Veins in Pregnancy
Authors: M. Drury
Journal: BMJ (1965)

MEDIALORThis patient, a woman 20 years old, pre- sented at this Department on 20 July 1964 with a lesion on the left cheek below the left eye.This was erythematous, slightly scaly, somewhat raised, and circumscribed by a ring of vesicles.It measured 4.25 cm. in diameter, and was of six weeks' duration.The patient's history was not contributory.Scrapings from the lesion revealed mycelium, and on culture yielded T. megninii.The maproscopical and microscopical morphology was typical of the species.Further- more, this strain demonstrated clearly, in two successive cultural tests, its absolute requirement for histidine on the synthetic basal medium de- vised by Georg for this purpose.'On this medium it is unable to produce any growth in the absence of histidine, whereas T. rubrum, which in many other respects it resembles, is able to grow well on this medium, irrespective of the presence or absence of histidine.This strain of T. megninii was sensitive in vitro at 27' C.to 10 jug./ml. of griseofulvin in Sabouraud glucose broth.For comparison with this strain, one of the isolates of T. megninii obtained by Dr. I. Sarkany and his colleagues at the Royal Free Hospital, London, was used in parallel series in these tests, and they were found to be similar in all respects.
Multicenter, Prospective and Retrospective Observational Cohort Study of Ponatinib in Patients with CML in Italy: Interim Analysis of the OITI Trial
Authors: Alessandra Iurlo, Mario Annunziata, Francesco Albano, Luigia Luciano, Raffaele Spadano, Anna Rita Scortechini, Massimiliano Bonifacio, Elisabetta Abruzzese, Monia Lunghi, Alessandra Malato, Nicola Di Renzo, Alfonso Piciocchi, Angela Pellegrino, Claudia Galimberti, Robin Foà, Massimo Breccia
Journal: Blood (2019)
Encyclopedic tumour analysis (ETA) guided combination regimens of hormone receptor antagonists with other systemic agents for treatment of refractory cancers
Authors: A. Vaid, T. Crook, A. Ranade, S. Limaye, D. Patil, D. Akolkar, V. Datta, R. Page, S. Schuster, C. Sims, R. Patil, A. Srinivasan, S. Apurwa, R. Datar
Journal: Annals of Oncology (2019)
Outcomes in Multiple Myeloma Patients Progressing on Lenalidomide Maintenance
Authors: Larysa Sanchez, Erin Moshier, Alexander Coltoff, Ali Mustafa, Darren Pan, Hearn Jay Cho, Sundar Jagannath, Deepu Madduri, Samir Parekh, Shambavi Richard, Joshua Richter, Ajai Chari
Journal: Blood (2019)
Gene Editing and mRNA-Based Therapy: Two Complementary Therapeutic Approaches for the Treatment of Patients with Xmen Disease
Authors: Julie Brault, Ezekiel Bello, Ronald J. Meis, Taylor Liu, Sherry M. Koontz, Kennichi Dowdell, Linhong Li, Cornell Allen, Narda Theobald, Janet Lee, Aaron B. Clark, Juan C. Ravell, Michael Lenardo, Gary A. Dahl, Harry L. Malech, Suk See De Ravin
Journal: Blood (2019)
Combined Scores from the EncephalApp Stroop Test, Number Connection Test B, and Serial Dotting Test Accurately Identify Patients With Covert Hepatic Encephalopathy
Authors: Xin Zeng, Li-Yuan Zhang, Qing Liu, Cui-Hua Lu, Jue Wei, Zhi-Wen Shi, Wei-Rong Huang, Li-Hong Qu, Fei Xu, Xiao-Hang Wang, Pei-Mei Shi, Yu Tan, Wei Tan, Zong-Li Yuan, Chun-Yan Xia, Yu-Lan Liu, Wei-Fen Xie
Journal: Clinical Gastroenterology and Hepatology (2019)
Outcomes at follow-up of negative colonoscopy in average risk population: systematic review and meta-analysis
Authors: Thomas Heisser, Le Peng, Korbinian Weigl, Michael Hoffmeister, Hermann Brenner
Journal: BMJ (2019)

Abstract Objective To review and summarise the evidence on the prevalence of colorectal adenomas and cancers at a follow-up screening colonoscopy after negative index colonoscopy, stratified by interval between examinations and by sex. Design Systematic review and meta-analysis of all available studies. Data sources PubMed, Web of Science, and Embase. Two investigators independently extracted characteristics and results of identified studies and performed standardised quality ratings. Eligibility criteria Studies assessing the outcome of a follow-up colonoscopy among participants at average risk for colorectal cancer with a negative previous colonoscopy (no adenomas). Results 28 studies were identified, including 22 cohort studies, five cross sectional studies, and one case-control study. Findings for an interval between colonoscopies of one to five, five to 10, and more than 10 years were reported by 17, 16, and three studies, respectively. Summary estimates of prevalences of any neoplasm were 20.7% (95% confidence interval 15.8% to 25.5%), 23.0% (18.0% to 28.0%), and 21.9% (14.9% to 29.0%) for one to five, five to 10, and more than 10 years between colonoscopies. Corresponding summary estimates of prevalences of any advanced neoplasm were 2.8% (2.0% to 3.7%), 3.2% (2.2% to 4.1%), and 7.0% (5.3% to 8.7%). Seven studies also reported findings stratified by sex. Summary estimates stratified by interval and sex were consistently higher for men than for women. Conclusions Although detection of any neoplasms was observed in more than 20% of participants within five years of a negative screening colonoscopy, detection of advanced neoplasms within 10 years was rare. Our findings suggest that 10 year intervals for colonoscopy screening after a negative colonoscopy, as currently recommended, may be adequate, but more studies are needed to strengthen the empirical basis for pertinent recommendations and to investigate even longer intervals. Study registration Prospero CRD42019127842.