HiSNAP trial—a multicentre, randomised, open-label, blinded end point, safety and efficacy trial of conventional (300 mg/kg) versus higher doses of acetylcysteine (450 mg/kg and 60... by Alasdair Gray, David M Wood, Jacqueline James, Keith Boath, Rajendra Raman, Matt Reed, Rachel O’Brien, Alison Grant, Sharon Tuck, Liza Keating, Craig Davidson, Christopher J Weir, Jonathan Carter, Stephen Lynch, James W Dear, Michael Eddleston, Lyle Moncur, Julia Grahamslaw, Katherine Oatey, Marianne Gillings, Lynsey Milne, Natalie Homer, Caroline Blackstock, Philippa Wright, Christopher Humphries, Alan Timmins, Laura Muir, Ruben Thanacoody, Ellise Clarke, Heather Robertson, Anna Miell, Chloe Haigh, Luisa Padovani, Karen Gray, Sandra Pirie, Christina Coventry, Amy Armstrong, Sian Irvine, Oliver Carlill, Donna Clark, Fraser Craig, Angela Crawford, Carlyn Davie, Judith Flemming, Marie-Claire Harris, Katy Letham, Malgorzata Litwin, Fiona McCurrach, Shona McDonald, Fraser McFadyen, Hazel Milligan, Victoria Minnis, Gillian Pickering, Rebecca Rielly, Emma-Beth Wilson, Lisa-Marie Butt, Kathleen Scullion, Claire Cheyne, Angela McGeough, Nikki McLaughlin, Fern Purdie, Sandee Beattie, Anna Borkowska, Katie Hamilton, Keith Jacques, Jeronimo Martin Ramirez, Vasilika Ntoko, Surinder Pandhor, Janine Ramsey, Maria Simpson

“…The study will first test the primary outcome on the HiSNAP Group 2 against Standard NAC; only if that is significant will HiSNAP Group 1 be tested against Standard NAC.Ethics and dissemination The HiSNAP trial has been approved by the East Midlands (Derby) Research Ethics Committee (reference 23/EM/0129), NHS Lothian Research and Development Department, and the MHRA. Results will be disseminated by peer-reviewed publication, conferences and linked on isrctn.com.Trial registration number ISRCTN17516192.…”
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Digital delivery of behavioural activation therapy to overcome depression and facilitate social and economic transitions of adolescents in South Africa (the DoBAt study): protocol... by Stephen Tollman, Kathleen Kahn, F Xavier Gómez-Olivé, Crick Lund, Alan Stein, Heather A O'Mahen, Eustasius Musenge, Sarah-Jayne Blakemore, Alastair van Heerden, Tholene Sodi, Bianca D Moffett, Julia R Pozuelo, Michelle Craske, Kate Orkin, Emma J Kilford, Mahreen Mahmud, Meghan Davis, Zamakhanya Makhanya, Tlangelani Baloyi, Daniel Mahlangu, Gabriele Chierchia, Sophie L Fielmann, Imraan Valodia

“…Secondary objectives are to pilot a range of cognitive, mental health, risky behaviour and socioeconomic measures; and to collect descriptive data on the feasibility of trial procedures to inform the development of a further larger trial.Ethics and dissemination This study has been approved by the University of the Witwatersrand Human Research Ethics Committee (MED20-05-011) and the Oxford Tropical Research Ethics Committee (OxTREC 34-20). …”
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Addressing Hypertension and Diabetes through Community-Engaged Systems (ANDES) in Puno, Peru: rationale and study protocol for a hybrid type 2 effectiveness and implementation rand... by Lindsay J. Underhill, Kendra N. Williams, Lucy Cordova-Ascona, Karina Campos, Lisa de las Fuentes, Mark D. Huffman, Joel Gittelsohn, Kenneth B. Schechtman, Zoila Vela-Clavo, Carla Tarazona-Meza, Laura K. Beres, Parker K. Acevedo, Abigail Barker, Nishadi Rajapakse, Makeda Williams, Veronica Tonwe, Aaloke Mody, Raquel Hurtado, Juan Carlos Mendoza, Gonzalo Cuentas, Elvin H. Geng, William Checkley, Victor G. Dávila-Román, Stella M. Hartinger-Peña

“…Furthermore, by addressing both hypertension and diabetes, the ANDES strategy supports integrated care approaches advocated by the WHO HEARTS technical package, ultimately enhancing health outcomes and reducing morbidity and mortality in the region. Trial registration ClinicalTrials.gov, ID: NCT05524987 , Addressing Hypertension and Diabetes through Community-Engaged Systems in Puno, Peru (ANDES study), prospectively registered on September 1, 2021.…”
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Influence of agroclimatic factors on the efficiency of multi-ovulation in cattle in the Peruvian tropics by Gleni Tatiana Segura Portocarrero, Gleni Tatiana Segura Portocarrero, Gleni Tatiana Segura Portocarrero, Nilton Luis Murga Valderrama, Rainer Marco Lopez Lapa, José Américo Saucedo Uriarte, Deiner Jhonel Gongora Bardales, Hugo Frias Torres, Annie Yoselin Poclín Rojas, Benjamin Depaz Hizo, Ronald Will Vasquez Tarrillo, Lizeth Amparo Heredia Vilchez, Gustavo Ampuero Trigoso

“…IntroductionAgroclimatic conditions are key determinants in the development of animal production and reproduction, with specific breed differences in vulnerability to environmental stress. …”
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Benefits and harms of perioperative high fraction inspired oxygen for surgical site infection prevention: a protocol for a systematic review and meta-analysis of individual patient... by Paul Myles, Markus W Hollmann, Janet Martin, Andrew Forbes, Benedetta Allegranzi, Kate Leslie, Robert Greif, Matthew TV Chan, Christian S Meyhoff, Marcel GW Dijkgraaf, Stijn W de Jonge, Carlos Ferrando, Kane Pryor, Andrea Kurz, Daniel I Sessler, Pascal Thibon, Marja Boermeester, Rick H Hulskes, Maedeh Zokaei Nikoo, Robert P Weenink, Ozan Akca, F Javier Belda, Gabriel M Gurman, Christina M Scifres, David S McKenna, Jannicke Mellin-Olsen

“…The results will be submitted to a peer-review journal.PROSPERO registration number CRD42018090261.…”
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Assessment of ovarian dysfunction induced by environmental toxins: a systematic review by Lu An, Yali Huang, Yunkai Wang, Shuting Shen, Xuexing Luo, Xiaoyan Liang, Xiaoyan Liang, Liming Lu, Chunzhi Tang, Jinglin Lin, Jinglin Lin, Ting Su, Ting Su, Meiqi Zhan, Meiqi Zhan, Dongying Wang, Dongying Wang, Jue Wang, Jue Wang, Xin Lai, Xin Lai, Yu Li, Yu Li

“…The findings underscore the importance of regular ovarian health monitoring, especially for women at higher risk due to occupational or environmental factors.Systematic review registrationPROSPERO CRD42024567744 (accessible at https://www.crd.york.ac.uk/prospero/display_record.php?…”
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Randomised controlled trial combining vitamin E-functionalised chocolate with physical exercise to reduce the risk of protein–energy malnutrition in predementia aged people: study... by Jose Viña, Chiara Milanese, Federico Schena, Anne McArdle, Malcolm J Jackson, Gabriele Di Sante, Cinzia Antognelli, Anna Pedrinolla, Masoud Isanejad, Desirée Bartolini, Consuelo Borras, Valentina Cavedon, Anna Migni, Cristina Mas-Bargues, Claudia Baschirotto, Roberto Modena, Alessandra Pistilli, Mario Rende, Anna Maria Stabile, Nicola Vincenzo Telesa, Sara Tortorella, Kay Hemmings, Eivind Wang, Massimo Venturelli, Francesco Galli

“…These activities include scientific workshops, public health awareness campaigns, project dedicated website and publication is scientific peer-review journals.Trial registration number NCT05343611.…”
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Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project by Lu Tang, Manish Arora, Wei Perng, Marcela Tamayo-Ortiz, Brisa N Sánchez, Alejandra Cantoral, John D Meeker, Dana C Dolinoy, Elizabeth F Roberts, Esperanza Angeles Martinez-Mier, Hector Lamadrid-Figueroa, Peter X K Song, Adrienne S Ettinger, Robert Wright, Lourdes Schnaas, Deborah J Watkins, Jaclyn M Goodrich, Robin C Garcia, Maritsa Solano-Gonzalez, Luis F Bautista-Arredondo, Adriana Mercado-Garcia, Howard Hu, Mauricio Hernandez-Avila, Martha Maria Tellez-Rojo, Karen E Peterson

“…Research has also expanded to include findings published on other toxicants such as those associated with personal care products and plastics (eg, phthalates, bisphenol A), other metals (eg, mercury, manganese, cadmium), pesticides (organophosphates) and fluoride; other biomarkers (eg, toxicant levels in plasma, hair and teeth); other outcomes (eg, sexual maturation, metabolic syndrome, dental caries); and identification of novel mechanisms via epigenetic and metabolomics profiling.Future plans As the ELEMENT mothers and children age, we plan to (1) continue studying the long-term consequences of toxicant exposure during the perinatal period on adolescent and young adult outcomes as well as outcomes related to the original ELEMENT mothers, such as their metabolic and bone health during perimenopause; and (2) follow the third generation of participants (children of the children) to study intergenerational effects of in utero exposures.Trial registration number NCT00558623.…”
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Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal (UNIVERSAL) study: a prospective observational cohort study protocol by Nicola White, James D Chalmers, Salman Siddiqui, Paul H Lee, Cyrus Daneshvar, James Raftery, Charles Roberts, Philip Mitchelmore, Kerensa Thorne, Stefan J Marciniak, Tom Wilkinson, Angelica Cazaly, Gareth Griffiths, Neil J Greening, Anna Freeman, Alexander Allen, Andrew Cook, Karl J Staples, Tommaso Morelli, Jacqueline Nuttall, James Myerson, Olivia Cox, Emma Chamberlain, Tristan William Clark, Martha Purcell, Pedro Rodrigues, Matthew Pavitt, Michael G Crooks, Emma Tilt, Emma Knox, Monica Gil, Max Ellis, Ingrid Seath, Sandy Aitken, Barbara Costa, Sarah Dudley

“…The study group will ensure that participants and their families are informed of the study findings promptly and in an accessible format.Trial registration number ISRCTN49183956.…”
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Cohort profile: the open, prospective Community-Based chronic Care Lesotho (ComBaCaL) cohort – design, baseline chronic disease risk factors and hypertension and diabetes care casc... by Matthias Briel, Thilo Burkard, Ravi Gupta, Frédérique Chammartin, Alain Amstutz, Thabo Ishmael Lejone, Eleonora Seelig, Irene Ayakaka, Mosa Tlahali, Matumaole Bane, Makhebe Khomolishoele, Tristan Lee, Niklaus Daniel Labhardt, Felix Gerber, Giuliana Sanchez-Samaniego, Thesar Tahirsylaj, Fabian Raeber, Mamakhala Chitja, Malebona Mathulise, Thuso Kabi, Mosoetsi Mokaeane, Malehloa Maphenchane, Manthabiseng Molulela, Mota Mota, Sesale Masike, Retselisitsoe Makabateng, Mamoronts’ane Sematle, Lebohang Sao, Sejojo Phaaroe, Malitaba Litaba, Madavida Mphunyane, Dave Brian Basler, Kevin Kindler, Pauline Grimm

“…This will provide further insights into the dynamics and interactions of chronic diseases and inform the development of future nested trials on innovative community-based prevention and care interventions.Trial registration number NCT05596773.…”
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Effectiveness of a multicomponent intervention to promote physical activity during the school day: rationale and methods of the MOVESCHOOL study by Francisco J. Bandera-Campos, Francisco J. Bandera-Campos, Alberto Grao-Cruces, Alberto Grao-Cruces, Daniel Camiletti-Moirón, Daniel Camiletti-Moirón, Fátima Martín-Acosta, Fátima Martín-Acosta, Raúl Muñoz-González, María González-Pérez, María González-Pérez, Abel Ruiz-Hermosa, Abel Ruiz-Hermosa, Miguel Vaquero-Solís, Miguel Vaquero-Solís, Carmen Padilla-Moledo, Carmen Padilla-Moledo, David Sánchez-Oliva, David Sánchez-Oliva, David Sánchez-Oliva

“…In addition, this research promises to provide a transformative experience for educators, equipping them with tools to promote the holistic development of their students, enriching their academic performance and enhancing their well-being.Clinical trial registrationClinicalTrials.gov, identifier NCT06254638.…”
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Understanding the association of intrapancreatic fat deposition with adiposity and components of metabolic syndrome in children and adolescents: a systematic review and meta-analys... by Claudia Izquierdo Rodríguez, Cristina Cadenas-Sanchez, José L. Santos, Jonatan R. Ruiz, María Medrano, Vicente Martínez-Vizcaíno, Michael I. Goran, Idoia Labayen

“…Longitudinal studies are necessary to understand the temporal dynamics of these associations and to determine the long-term impact of intrapancreatic fat deposition on the risk of developing type 2 diabetes and cardiovascular diseases. …”
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Facilitators, barriers, and guidance to successful implementation of multidisciplinary transitional care interventions: A qualitative systematic review using the consolidated frame... by Romain Collet, Juul van Grootel, Marike van der Leeden, Marike van der Schaaf, Johanna van Dongen, Suzanne Wiertsema, Edwin Geleijn, Mel Major, Raymond Ostelo

“…Further research should identify effective implementation strategies, considering the pre-, post-discharge, and general factors identified. Registration: The protocol was registered in PROSPERO (CRD42023421423). …”
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HS-10375, a selective EGFR C797S tyrosine kinase inhibitor, in advanced non–small cell lung cancer by Jianhua Zhan, Jinhui Xue, Lin Wu, Zhiye Zhang, Qiming Wang, Yuxiang Ma, Yan Huang, Yunpeng Yang, Yuanyuan Zhao, Wenfeng Fang, Yang Zhang, Qianwen Liu, Wen Xu, Yan Yang, Zhenming Chen, Baili Song, Danni Sun, Xia Sun, Peng Gao, Hongyun Zhao, Li Zhang

“…Abstract Background The C797S mutation is one of the most common mechanisms of acquired resistance to third generation EGFR TKIs, yet no approved therapies have been available to target it. Here we developed a novel selective EGFR C797S inhibitor, HS-10375, and report the results of pre-clinical research and the first-in-human phase 1 trial. …”
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MHC-restricted phosphopeptide antigens: preclinical validation and first-in-humans clinical trial in participants with high-risk melanoma by Mark E Smolkin, Gina R Petroni, Kimberly A Chianese-bullock, Kelly T Smith, Geoffrey Weiss, Nico Buettner, Mark Cobbold, Jeffrey Shabanowitz, Nikole Varhegyi, Elizabeth Gaughan, Victor H Engelhard, Rebecca C Obeng, Kara L Cummings, Angela L Ambakhutwala, Amanda Lulu, Paisley Myers, Keira E Mahoney, Emily H Hall, Kathleen Haden, Donald F Hunt, Craig L Slingluff, Jr

“…Future studies will define ways to further enhance the magnitude and durability of phosphopeptide-specific immune responses.Trial registration number NCT01846143…”
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Precision computerised cognitive behavioural therapy (cCBT) intervention for adolescents with depression (SPARX-UK): protocol for the process evaluation of a pilot randomised contr... by Charlotte Lucy Hall, Chris Hollis, Kareem Khan, Peter Fonagy, Kirsty Sprange, Cathy Creswell, Yi Yang, Vibhore Prasad, Kapil Sayal, Nitish Jawahar, Ellen Townsend, Dorothee Auer, Praveetha Patalay, Aja Murray, Yvonne Kelly, Boliang Guo, Christopher R Tench, Paul Stallard, Louise Arseneault, Sieun Lee, Sally Merry, Charlotte Hall, Jo Gregory, Rory O’Connor, Emma Nielsen, Edmund Sonuga-Barke, Hannah Wright, Petr Slovak, Emily Lloyd, Josimar De Alcantara Mendes, Carolyn Ten Holter, Marina Jirotka, Aaron Kandola, Sonia Livingstone, Kasia Kostryka-Allchorne, Jake Bourgaize, Mariya Stoilova, Marianne Etherson, Chris Greenhalgh, Jim Warren, Vajisha Wanniarachchi, Kevin Glover, Mathijs Lucassen, Karolina Stasiak, Camilla Babbage, Adam Parker, Joanna Lockwood, Elvira Perez Vallejos, Rebecca Woodcock, Sarah Doherty, Lucy-Paige Willingham, Camilla May Babbage, Matthew Jeffery, Peiyao Tang, Holly Griffiths, Lily Roberts, A. Jess Williams, Lucy Hitcham

“…We plan to publish the findings of the process evaluation and the wider project in peer-reviewed journals, as well as disseminate via academic conferences.Trial registration number ISRCTN: ISRCTN15124804. Registered on 16 January 2023, https://www.isrctn.com/ISRCTN15124804.…”
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Denosumab as an immune modulator in HER2-negative early breast cancer: results of the window-of-opportunity D-BIOMARK clinical trial by Andrea Vethencourt, Eva M. Trinidad, Eduard Dorca, Anna Petit, M. Teresa Soler-Monsó, Marina Ciscar, Alexandra Barranco, Gema Pérez-Chacón, María Jimenez, Mario Rodríguez, Clara Gomez-Aleza, Elvira Purqueras, Enrique Hernández-Jiménez, Ander Urruticoechea, Idoia Morilla, Isaac Subirana, Amparo García-Tejedor, Miguel Gil-Gil, Sonia Pernas, Catalina Falo, Eva Gonzalez-Suarez

“…Preclinical models suggest that inhibition of RANK signaling can prevent mammary tumor development by reducing proliferation and tumor cell survival. …”
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Sodium-glucose co-transporter-2 inhibitors in patients with chronic kidney disease with or without type 2 diabetes: systematic review and meta-analysis by Gordon Guyatt, Arnav Agarwal, Thomas Agoritsas, Haoming Tian, Sheyu Li, Chang Xu, Ping Fu, Qingyang Shi, Xiaoxi Zeng, Per Olav Vandvik, Xinyu Zou, Yunhe Mao, Qinbo Yang, Xianghang Luo, Belen Ponte

“…Absolute benefits and harms stratified by risk and associated with SGLT-2 inhibitors should inform individual decision making at the patient level.Systematic review registration PROSPERO CRD42022325483.…”
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Leveraging infant visit PrEP screening INtegration & tasK shifting to improve post-partum HIV prevention in Malawi (LINK): a cluster-randomized trial evaluation of a postpartum HIV... by Sarah E. Rutstein, Valerie A. Lucas, Mina C. Hosseinipour, Michael E. Herce, Jessie Edwards, Caitlin Cassidy, Jimmy Villiera, Funny Kamanga, Maganizo Chagomerana, Joep J. van Oosterhout, Elijah Chikuse, Ethel Rambiki, Agness Thawani, Bridget Malewezi, Lazola Makhupula, Clement Udedi, Patrick Mbulaje, Mitch Matoga, Wiza Kumwenda, Tisungane Mvalo, Agatha Bula, Lovemore Nkhalamba, Innocent Mofolo, Lameck Chinula, Virginia Thonyiwa, Owen Kumwenda, Mike Nenani Chisema, Irving F. Hoffman, William C. Miller, Vivian F. Go, Brian Pence, Madeleine A. Squibb, Friday Saidi

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A phase I, open-label, multicentre, first-in-human study to evaluate safety, pharmacokinetics and efficacy of AMG 404, a PD-1 inhibitor, in patients with advanced solid tumours by Yasutoshi Kuboki, Hendrik-Tobias Arkenau, Vivek Subbiah, Timothy Price, Gerald Falchook, Hans Prenen, Rafal Dziadziuszko, Hansen Wong, Iwona Lugowska, Daniel Tan, Weibing Shi, Ryota Shibaki, Min Hee Hong, Sant P Chawla, Jose G Monzon, Mun Hui, Caio Max Rocha Lima, Kejia Wang, Antreas Hindoyan, Mira Kistler

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