tbuckley/cabot-search huggingface dataset:
A combined nanotherapeutic approach targeting farnesoid X receptor, ferroptosis, and fibrosis for nonalcoholic steatohepatitis treatment
Authors: Jiangtao Fu, Pingping Zhang, Zhiguo Sun, Guodong Lu, Qi Cao, Yiting Chen, Wenbin Wu, Jiabao Zhang, Chunlin Zhuang, Chunquan Sheng, Jiajun Xu, Ying Lu, Pei Wang
Journal: Acta Pharmaceutica Sinica B (2024)

Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with favorable effects on fatty and glucose metabolism, has been considered the leading candidate drug for nonalcoholic steatohepatitis (NASH) treatment. However, its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major drawback. Ferroptosis, a newly recognized form of cell death characterized by uncontrolled lipid peroxidation, is involved in the progression of NASH. Nitric oxide (NO) is a versatile biological molecule that can degrade extracellular matrix. In this study, we developed a PEGylated thiolated hollow mesoporous silica nanoparticles (MSN) loaded with OCA, as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol (ONL@MSN). Biochemical analyses, histology, multiplexed flow cytometry, bulk-tissue RNA sequencing, and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle (ONL@MSN) in a mouse NASH model. Compared with the OCA-loaded nanoparticles (O@MSN), ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ferroptosis. ONL@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis, inhibition of immune response/lipid peroxidation, and correction of microbiota dysbiosis. These findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR, ferroptosis, and fibrosis.
Integrative single‐cell expression and functional studies unravels a sensitization to cytarabine‐based chemotherapy through HIF pathway inhibition in AML leukemia stem cells
Authors: Talia Velasco‐Hernandez, Juan L. Trincado, Meritxell Vinyoles, Adria Closa, Alba Martínez‐Moreno, Francisco Gutiérrez‐Agüera, Oscar Molina, Virginia C. Rodríguez‐Cortez, Pau Ximeno‐Parpal, Narcís Fernández‐Fuentes, Paolo Petazzi, Sergi Beneyto‐Calabuig, Lars Velten, Paola Romecin, Raquel Casquero, Fernando Abollo‐Jiménez, Rafael D. de la Guardia, Patricia Lorden, Alex Bataller, Hélène Lapillonne, Ronald W. Stam, Susana Vives, Montserrat Torrebadell, Jose L. Fuster, Clara Bueno, Jean‐Emmanuel Sarry, Eduardo Eyras, Holger Heyn, Pablo Menéndez
Journal: HemaSphere (2024)

Relapse remains a major challenge in the clinical management of acute myeloid leukemia (AML) and is driven by rare therapy-resistant leukemia stem cells (LSCs) that reside in specific bone marrow niches. Hypoxia signaling maintains cells in a quiescent and metabolically relaxed state, desensitizing them to chemotherapy. This suggests the hypothesis that hypoxia contributes to the chemoresistance of AML-LSCs and may represent a therapeutic target to sensitize AML-LSCs to chemotherapy. Here, we identify HIF
Curiosity and the dynamics of optimal exploration
Authors: Francesco Poli, Jill X. O’Reilly, Rogier B. Mars, Sabine Hunnius
Journal: Trends in Cognitive Sciences (2024)

What drives our curiosity remains an elusive and hotly debated issue, with multiple hypotheses proposed but a cohesive account yet to be established. This review discusses traditional and emergent theories that frame curiosity as a desire to know and a drive to learn, respectively. We adopt a model-based approach that maps the temporal dynamics of various factors underlying curiosity-based exploration, such as uncertainty, information gain, and learning progress. In so doing, we identify the limitations of past theories and posit an integrated account that harnesses their strengths in describing curiosity as a tool for optimal environmental exploration. In our unified account, curiosity serves as a 'common currency' for exploration, which must be balanced with other drives such as safety and hunger to achieve efficient action.
Robotic versus open partial pancreatoduodenectomy (EUROPA): a randomised controlled stage 2b trial
Authors: Rosa Klotz, André L. Mihaljevic, Yakup Kulu, Anja Sander, Christina Klose, Rouven Behnisch, Maximilian C. Joos, Eva Kalkum, Felix Nickel, Phillip Knebel, Frank Pianka, Markus K. Diener, Markus W. Büchler, Thilo Hackert
Journal: The Lancet Regional Health - Europe (2024)

Open partial pancreatoduodenectomy (OPD) represents the current gold standard of surgical treatment of a wide range of diseases of the pancreatic head but is associated with morbidity in around 40% of cases. Robotic partial pancreatoduodenectomy (RPD) is being used increasingly, yet, no randomised controlled trials (RCTs) of RPD versus OPD have been published, leaving a low level of evidence to support this practice. This investigator-initiated, exploratory RCT with two parallel study arms was conducted at a high-volume pancreatic centre in line with IDEAL recommendations (stage 2b). Patients scheduled for elective partial pancreatoduodenectomy (PD) for any indication were randomised (1:1) to RPD or OPD with a centralised web-based tool. The primary endpoint was postoperative cumulative morbidity within 90 days, assessed via the Comprehensive Complication Index (CCI). Biometricians were blinded to the intervention, but patients and surgeons were not. The trial was registered prospectively (DRKS00020407). Between June 3, 2020 and February 14, 2022, 81 patients were randomly assigned to RPD (n = 41) or OPD (n = 40), of whom 62 patients (RPD: n = 29, OPD: n = 33) were analysed in the modified intention to treat analysis. Four patients in the OPD group were randomised, but did not undergo surgery in our department and one patient was excluded in the RPD group due to other reason. Nine patients in the RPD group and 3 patients in the OPD were excluded from the primary analysis because they did not undergo PD, but rather underwent other types of surgery. The CCI after 90 days was comparable between groups (RPD: 34.02 ± 23.48 versus OPD: 36.45 ± 27.65, difference in means [95% CI]: −2.42 [−15.55; 10.71], p = 0.713). The RPD group had a higher incidence of grade B/C pancreas-specific complications compared to the OPD group (17 (58.6%) versus 11 (33.3%); difference in rates [95% CI]: 25.3% [1.2%; 49.4%], p = 0.046). The only complication that occurred significantly more often in the RPD than in the OPD group was clinically relevant delayed gastric emptying. Procedure-related and overall hospital costs were significantly higher and duration of surgery was longer in the RPD group. Blood loss did not differ significantly between groups. The intraoperative conversion rate of RPD was 23%. Overall 90-day mortality was 4.8% without significant differences between RPD and OPD. In the setting of a very high-volume centre, both RPD and OPD can be considered safe techniques. Further confirmatory multicentre RCTs are warranted to uncover potential advantages of RPD in terms of perioperative and long-term outcomes. Federal Ministry of Education and Research (BMBF: 01KG2010).
Intraoperative Anemia Mediates Sex Disparity in Operative Mortality After Coronary Artery Bypass Grafting
Authors: Lamia Harik, Robert H. Habib, Arnaldo Dimagli, Mohamed Rahouma, Roberto Perezgrovas-Olaria, Giovanni Jr Soletti, Talal Alzghari, Kevin R. An, Lisa Q. Rong, Sigrid Sandner, C. Noel Bairey-Merz, Bjorn Redfors, Leonard Girardi, Mario Gaudino
Journal: Journal of the American College of Cardiology (2024)
Lipoprotein(a) and Major Adverse Cardiovascular Events in Patients With or Without Baseline Atherosclerotic Cardiovascular Disease
Authors: Adam N. Berman, David W. Biery, Stephanie A. Besser, Avinainder Singh, Arthur Shiyovich, Brittany N. Weber, Daniel M. Huck, Sanjay Divakaran, Jon Hainer, Gurleen Kaur, Michael J. Blaha, Christopher P. Cannon, Jorge Plutzky, James L. Januzzi, John N. Booth, J. Antonio G. López, Shia T. Kent, Khurram Nasir, Marcelo F. Di Carli, Deepak L. Bhatt, Ron Blankstein
Journal: Journal of the American College of Cardiology (2024)
Use of radiotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study
Authors: Sean McPhail, Matthew E Barclay, Ruth Swann, Shane A Johnson, Riaz Alvi, Andriana Barisic, Oliver Bucher, Nicola Creighton, Cheryl A Denny, Ron A Dewar, David W Donnelly, Jeff J Dowden, Laura Downie, Norah Finn, Anna T Gavin, Steven Habbous, Dyfed W Huws, S Eshwar Kumar, Leon May, Carol A McClure, David S Morrison, Bjørn Møller, Grace Musto, Yngvar Nilssen, Nathalie Saint-Jacques, Sabuj Sarker, Lorraine Shack, Xiaoyi Tian, Robert JS Thomas, Haiyan Wang, Ryan R Woods, Hui You, Bin Zhang, Georgios Lyratzopoulos, Damien Bennett, John Butler, David A Cameron, Cindy Chew, Tom Crosby, Brooke Filsinger, Christian J Finley, Katharina Forster, Sharon Fung, Bo Green, Elba Gomez-Navas, Eric Gutierrez, Jihee Han, Samantha Harrison, Mark Lawler, Alana L Little, Jason R Pantarotto, Stuart J Peacock, Isabelle Ray-Coquard, Catherine S Thomson, Janet L Warlow, Emma Whitfield
Journal: The Lancet Oncology (2024)
Switching to dolutegravir plus rilpivirine versus maintaining current antiretroviral therapy regimen in virologically suppressed people with HIV-1 and the Lys103Asn (K103N) mutation: 48-week results from a randomised, open-label pilot clinical trial
Authors: Graeme Moyle, Lambert Assoumou, Nathalie de Castro, Frank A Post, Adrian Curran, Stefano Rusconi, Stephane De Wit, Christoph Stephan, François Raffi, Margaret Johnson, Mar Masia, Jaime Vera, Bryn Jones, Richard Grove, Carl Fletcher, Annie Duffy, Kellie Morris, Anton Pozniak, Graeme Moyle, Nathalie de Castro, Frank Post, Adrian Curran, Stefano Rusconi, Stephane De Wit, Christoph Stephan, François Raffi, Margaret Johnson, Mar Masia, Jaime Vera, Alan Winston, Stephen Kegg, Laura Waters, Chole Orkin, Andrew Ustianowski, Iain Reeves, Clifford Leen, Meghan Perry, Joaquin Portilla, Jose Luis Blanco, Rocio Montejaro, Pere Domingo, Jean Michel Molina, Christine Katlama, Philippe Morlat, Christopher Kenyon, Massimo Puoti, Giuliano Rizzardini, Antonella Castagna, Francesco Castelli, Andrea Giacomelli, Jürgen Rockstroh, Stefan Esser, Christian Hoffmann, Patrick Mallon
Journal: The Lancet HIV (2024)
Lessons learned from postmarketing withdrawals of expedited approvals for oncology drug indications
Authors: Simone N Koole, Atse H Huisman, Lonneke Timmers, Hans M Westgeest, Edwin van Breugel, Gabe S Sonke, Sahar Barjesteh van Waalwijk van Doorn-Khosrovani
Journal: The Lancet Oncology (2024)
Women lead the way in the HIV response
Authors: None The Lancet HIV
Journal: The Lancet HIV (2024)

March 8 marks International Women's Day—the annual event that gives focus to issues including gender equity and inclusion, reproductive rights, and violence against women. In the field of HIV, the concerns posed by International Women's Day resonate particularly strongly. Women are disproportionately affected by HIV globally, and in some of the hardest hit regions, women bear the brunt of the epidemic in terms of both disease burden and care for those affected. UNAIDS estimates that 53% of people living with HIV in 2022 were women and girls.
Stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a non-randomised phase 2 trial
Authors: Shankar Siva, Mathias Bressel, Mark Sidhom, Swetha Sridharan, Ben G L Vanneste, Ryan Davey, Rebecca Montgomery, Jeremy Ruben, Farshad Foroudi, Braden Higgs, Charles Lin, Avi Raman, Nicholas Hardcastle, Michael S Hofman, Richard De Abreu Lourenco, Mark Shaw, Pascal Mancuso, Daniel Moon, Lih-Ming Wong, Nathan Lawrentschuk, Simon Wood, Nicholas R Brook, Tomas Kron, Jarad Martin, David Pryor
Journal: The Lancet Oncology (2024)
Angiotensin Receptor-Neprilysin Inhibition in Patients With STEMI vs NSTEMI
Authors: Douglas L. Mann, Johny Nicolas, Brian Claggett, Zi Michael Miao, Christopher B. Granger, Prafulla Kerkar, Lars Køber, Eldrin F. Lewis, John J.V. McMurray, Aldo P. Maggioni, Julio Núñez, Mpiko Ntsekhe, Jean-Lucien Rouleau, David Sim, Scott D. Solomon, Philippe Gabriel Steg, Peter van der Meer, Eugene Braunwald, Marc A. Pfeffer, Roxana Mehran
Journal: Journal of the American College of Cardiology (2024)
Implications of Atrial Fibrillation for Guideline-Directed Therapy in Patients With Heart Failure
Authors: Joshua D. Newman, Eileen O’Meara, Michael Böhm, Gianluigi Savarese, Patricia R. Kelly, Orly Vardeny, Larry A. Allen, Patrizio Lancellotti, Stephen S. Gottlieb, Zainab Samad, Alanna A. Morris, Nihar R. Desai, Giuseppe M.C. Rosano, John R. Teerlink, Clara Saldarriaga Giraldo, JoAnn Lindenfeld
Journal: Journal of the American College of Cardiology (2024)
Pivekimab sunirine (IMGN632), a novel CD123-targeting antibody–drug conjugate, in relapsed or refractory acute myeloid leukaemia: a phase 1/2 study
Authors: Naval G Daver, Pau Montesinos, Daniel J DeAngelo, Eunice S Wang, Nikolaos Papadantonakis, Elisabetta Todisco, Kendra L Sweet, Naveen Pemmaraju, Andrew A Lane, Laura Torres-Miñana, James E Thompson, Marina Y Konopleva, Callum M Sloss, Krystal Watkins, Gaurav Bedse, Yining Du, Kara E Malcolm, Patrick A Zweidler-McKay, Hagop M Kantarjian
Journal: The Lancet Oncology (2024)
Surveillance Stress Testing After Percutaneous Intervention for Patients With Multivessel or Left Main Coronary Disease
Authors: Joong Min Lee, Hoyun Kim, Young-Sun Park, Ha Hye Jo, So-Min Lim, Jinho Lee, Yeonwoo Choi, Do-Yoon Kang, Jung-Min Ahn, Seonok Kim, Yong-Hoon Yoon, Seung-Ho Hur, Cheol Hyun Lee, Won-Jang Kim, Se Hun Kang, Chul Soo Park, Bong-Ki Lee, Jung-Won Suh, Jae Woong Choi, Kee-Sik Kim, Su Nam Lee, Seung-Jung Park, Duk-Woo Park
Journal: Journal of the American College of Cardiology (2024)
Eligibility for and Preventive Potential of Semaglutide in Overweight and Obese Patients With Myocardial Infarction
Authors: Malene K. Hansen, Kevin K.W. Olesen, Christine Gyldenkerne, Pernille G. Thrane, Nina Stødkilde-Jørgensen, Martin B. Mortensen, Michael Maeng
Journal: Journal of the American College of Cardiology (2024)
Corrigendum to “Mortality in metabolic dysfunction-associated steatotic liver disease: A nationwide population-based cohort study” [Metabolism, Volume 152, March 2024, 155789]
Authors: Eugene Han, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Sang Hoon Ahn, Yong-Ho Lee, Seung Up Kim
Journal: Metabolism (2024)
Use of chemotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study
Authors: Sean McPhail, Matthew E Barclay, Shane A Johnson, Ruth Swann, Riaz Alvi, Andriana Barisic, Oliver Bucher, Nicola Creighton, Cheryl A Denny, Ron A Dewar, David W Donnelly, Jeff J Dowden, Laura Downie, Norah Finn, Anna T Gavin, Steven Habbous, Dyfed W Huws, Leon May, Carol A McClure, Bjørn Møller, Grace Musto, Yngvar Nilssen, Nathalie Saint-Jacques, Sabuj Sarker, Lorraine Shack, Xiaoyi Tian, Robert J S Thomas, Catherine S Thomson, Haiyan Wang, Ryan R Woods, Hui You, Georgios Lyratzopoulos, Alon D Altman, Damien Bennett, John Butler, David A Cameron, Tom Crosby, Llion Davies, Elijah Dixon, Brooke Filsinger, Katharina Forster, Sharon Fung, Elba Gomez Navas, Marianne G Guren, Jihee Han, Louise Hanna, Samantha Harrison, Mark Lawler, Alana L Little, Tom Mala, Neil Merrett, David S Morrison, Gregg Nelson, Stuart J Peacock, David T Ransom, Isabelle Ray-Coquard, Janet L Warlow, Emma Whitfield, John R Zalcberg
Journal: The Lancet Oncology (2024)
Tailoring therapeutics via a systematic beneficial elements comparison between photosynthetic bacteria-derived OMVs and extruded nanovesicles
Authors: Tingshan Xiao, Yichuan Ma, Ziyang Zhang, Yixin Zhang, Yu Zhao, Xiaohan Zhou, Xueyi Wang, Kun Ge, Junshu Guo, Jinchao Zhang, Zhenhua Li, Huifang Liu
Journal: Bioactive Materials (2024)

Photosynthetic bacteria (PSB) has shown significant potential as a drug or drug delivery system owing to their photothermal capabilities and antioxidant properties. Nevertheless, the actualization of their potential is impeded by inherent constraints, including their considerable size, heightened immunogenicity and compromised biosafety. Conquering these obstacles and pursuing more effective solutions remains a top priority. Similar to extracellular vesicles, bacterial outer membrane vesicles (OMVs) have demonstrated a great potential in biomedical applications. OMVs from PSB encapsulate a rich array of bioactive constituents, including proteins, nucleic acids, and lipids inherited from their parent cells. Consequently, they emerge as a promising and practical alternative. Unfortunately, OMVs have suffered from low yield and inconsistent particle sizes. In response, bacteria-derived nanovesicles (BNVs), created through controlled extrusion, adeptly overcome the challenges associated with OMVs. However, the differences, both in composition and subsequent biological effects, between OMVs and BNVs remain enigmatic. In a groundbreaking endeavor, our study meticulously cultivates PSB-derived OMVs and BNVs, dissecting their nuances. Despite minimal differences in morphology and size between PSB-derived OMVs and BNVs, the latter contains a higher concentration of active ingredients and metabolites. Particularly noteworthy is the elevated levels of lysophosphatidylcholine (LPC) found in BNVs, known for its ability to enhance cell proliferation and initiate downstream signaling pathways that promote angiogenesis and epithelialization. Importantly, our results indicate that BNVs can accelerate wound closure more effectively by orchestrating a harmonious balance of cell proliferation and migration within NIH-3T3 cells, while also activating the EGFR/AKT/PI3K pathway. In contrast, OMVs have a pronounced aptitude in anti-cancer efforts, driving macrophages toward the M1 phenotype and promoting the release of inflammatory cytokines. Thus, our findings not only provide a promising methodological framework but also establish a definitive criterion for discerning the optimal application of OMVs and BNVs in addressing a wide range of medical conditions.
Surrogate endpoints in clinical trials of p16-positive squamous cell carcinoma of the oropharynx: an individual patient data meta-analysis
Authors: Laila A Gharzai, Emily Morris, Krithika Suresh, Phuc Felix Nguyen-Tân, David I Rosenthal, Maura L Gillison, Paul M Harari, Adam S Garden, Shlomo Koyfman, Jimmy J Caudell, Christopher U Jones, Darrion L Mitchell, Greg Krempl, John A Ridge, Michael F Gensheimer, James A Bonner, Edith Filion, Neal E Dunlap, William A Stokes, Quynh-Thu Le, Pedro Torres-Saavedra, Michelle Mierzwa, Matthew J Schipper
Journal: The Lancet Oncology (2024)
Omalizumab for the Treatment of Multiple Food Allergies
Authors: Robert A. Wood, Alkis Togias, Scott H. Sicherer, Wayne G. Shreffler, Edwin H. Kim, Stacie M. Jones, Donald Y.M. Leung, Brian P. Vickery, J. Andrew Bird, Jonathan M. Spergel, Ahmar Iqbal, Julie Olsson, Monica Ligueros-Saylan, Alkaz Uddin, Agustin Calatroni, Charmaine Marquis Huckabee, Nicole H. Rogers, Nancy Yovetich, Jennifer Dantzer, Kim Mudd, Julie Wang, Marion Groetch, David Pyle, Corinne A. Keet, Michael Kulis, Sayantani B. Sindher, Andrew Long, Amy M. Scurlock, Bruce J. Lanser, Tricia Lee, Christopher Parrish, Terri Brown-Whitehorn, Amanda K. Rudman Spergel, Maria Veri, Sanaz Daneshfar Hamrah, Erica Brittain, Julian Poyser, Lisa M. Wheatley, R. Sharon Chinthrajah
Journal: New England Journal of Medicine (2024)

Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy.
Comparing one dose of HPV vaccine in girls aged 9–14 years in Tanzania (DoRIS) with one dose in young women aged 15–20 years in Kenya (KEN SHE): an immunobridging analysis of randomised controlled trials
Authors: Kathy Baisley, Troy J Kemp, Nelly R Mugo, Hilary Whitworth, Maricianah A Onono, Betty Njoroge, Jackton Indangasi, Elizabeth A Bukusi, Priya R Prabhu, Paul Mutani, Denise A Galloway, David Mwanzalime, Saidi Kapiga, Charles J Lacey, Richard J Hayes, John Changalucha, Ligia A Pinto, Ruanne V Barnabas, Deborah Watson-Jones
Journal: The Lancet Global Health (2024)

BackgroundThe first randomised controlled trial of single-dose human papillomavirus (HPV) vaccine efficacy, the Kenya single-dose HPV-vaccine efficacy (KEN SHE) trial, showed greater than 97% efficacy against persistent HPV16 and HPV18 infection at 36 months among women in Kenya. We compared antibody responses after one dose of HPV vaccine in the Dose Reduction Immunobridging and Safety Study (DoRIS), the first randomised trial of the single- dose regimen in girls aged 9–14 years, the target age range for vaccination, with those after one dose of the same vaccine in KEN SHE.MethodsIn the DoRIS trial, 930 girls aged 9–14 years in Tanzania were randomly assigned to one, two, or three doses of the 2-valent vaccine (Cervarix) or the 9-valent vaccine (Gardasil-9). The proportion seroconverting and geometric mean concentrations (GMCs) at month 24 after one dose were compared with those in women aged 15–20 years who were randomly assigned to one dose of the same vaccines at the same timepoint in KEN SHE. Batched samples were tested together by virus-like particle ELISA for HPV16 and HPV18 IgG antibodies. Non-inferiority of GMC ratios (DoRIS trial:KEN SHE) was predefined as a lower bound of the 95% CI less than 0·50.FindingsMonth 24 HPV16 and HPV18 antibody GMCs in DoRIS were similar or higher than those in KEN SHE. 2-valent GMC ratios were 0·90 (95% CI 0·72–1·14) for HPV16 and 1·02 (0·78–1·33) for HPV18. 9-valent GMC ratios were 1·44 (95% CI 1·14–1·82) and 1·47 (1·13–1·90), respectively. Non-inferiority of antibody GMCs and seropositivity was met for HPV16 and HPV18 for both vaccines.InterpretationHPV16 and HPV18 immune responses in young girls 24 months after a single dose of 2-valent or 9-valent HPV vaccine were comparable to those in young women who were randomly assigned to a single dose of the same vaccines and in whom efficacy had been shown. A single dose of HPV vaccine, when given to girls in the target age range for vaccination, induces immune responses that could be effective against persistent HPV16 and HPV18 infection at least two years after vaccination.FundingThe UK Department of Health and Social Care, the Foreign, Commonwealth, & Development Office, the Global Challenges Research Fund, the UK Medical Research Council and Wellcome Trust Joint Global Health Trials scheme, the Bill and Melinda Gates Foundation, the US National Cancer Institute; the US National Institutes of Health, and the Francis and Dorothea Reed Endowed Chair in Infectious Diseases.TranslationFor the KiSwahili translation of the abstract see Supplementary Materials section.