tbuckley/cabot-search huggingface dataset:
Rezivertinib versus gefitinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (REZOR): a multicentre, double-blind, randomised, phase 3 study
Authors: Yuankai Shi, Yanzhen Guo, Xingya Li, Lin Wu, Zhaohong Chen, Sheng Yang, Minghong Bi, Yanqiu Zhao, Wenxiu Yao, Huiqing Yu, Ke Wang, Wenhua Zhao, Meili Sun, Liangming Zhang, Zhiyong He, Yingcheng Lin, Jianhua Shi, Bo Zhu, Lijun Wang, Yueyin Pan, Huaqiu Shi, Shenghua Sun, Meiling Wen, Rui Zhou, Shuliang Guo, Zhigang Han, Tienan Yi, Hua Zhang, Shundong Cang, Zhuang Yu, DianSheng Zhong, Jiuwei Cui, Jian Fang, Jinghua Gao, Manxiang Li, Rui Ma, Mingyan Jiang, Jianwen Qin, Yongqian Shu, Feng Ye, Sheng Hu, Wen Li, Hong Lu, Minglei Yang, Shanyong Yi, Yan Zhang, Yun Fan, Hongbo Ji, Zheng Liu, Haitao Wang, Xiangdong Zhou, Don Zhang, Jirong Peng, Haijiao Shen, Feng Gao, Tingting Wang, Anqi Zhou
Journal: The Lancet Respiratory Medicine (2025)
Cancer screening: putting people at the centre
Authors: None The Lancet Public Health
Journal: The Lancet Public Health (2025)

Feb 4 marks World Cancer Day—an opportunity to raise awareness about cancer and to reflect on the latest trends, challenges, and hopes. Acknowledging that cancer is not simply a medical diagnosis, but rather a unique personal story, the World Cancer Day campaign places people at the centre and calls for a people-centred approach to cancer.
Survival in patients with rheumatoid arthritis and recently diagnosed early-stage colorectal, lung, or prostate cancer receiving tumour necrosis factor inhibitors: a retrospective cohort study
Authors: Juan I Ruiz, Xiudong Lei, Sharon H Giordano, Hui Zhao, Suja S Rajan, Heather Lin, Maria E Suarez-Almazor
Journal: The Lancet Rheumatology (2025)
Prevalence of severe mental illness among people in prison across 43 countries: a systematic review and meta-analysis
Authors: Christina Emilian, Noura Al-Juffali, Seena Fazel
Journal: The Lancet Public Health (2025)

SummaryBackgroundPrison populations have been increasing worldwide. Previous studies suggest that there is a high burden of psychiatric morbidity in people in prison, but, to our knowledge, the last published meta-analysis of prevalence is more than a decade old. We aimed to describe the pooled prevalence of depression, psychosis, bipolar disorder, and schizophrenia spectrum disorders for people who are incarcerated.MethodsIn this updated systematic review and meta-analysis, we searched six databases and grey literature published from database inception until Aug 8, 2024, with no language or geographical restrictions. We included primary quantitative studies that reported the prevalence of depression and psychotic disorders in the unselected prison population, based their diagnoses on clinical examination or from interviews and by the use of validated diagnostic instruments, met standardised criteria of the ICD or the Diagnostic and Statistical Manual of Mental Disorders for the diagnoses, and provided pooled prevalences for psychosis in the previous 6 months and clinical depression in the previous 2 weeks to 1 month. We excluded studies that used selected samples or were only qualitative. We investigated bipolar and schizophrenia spectrum disorders as separate diagnostic subcategories. We synthesised studies using random-effects meta-analysis and explored heterogeneity with meta-regression and subgroup analyses. The protocol is registered with PROSPERO, CRD42022378568.FindingsWe identified 131 publications reporting the prevalence of mental illness in 58 838 people in prison in 43 countries. We estimated that the prevalence of depression was 12·8% (95% CI 11·1–14·6) and for any psychosis was 4·1% (3·6–4·7). For diagnostic subcategories, we found that the prevalence of bipolar disorder was 1·7% (1·0–2·6) and schizophrenia spectrum disorders was 3·6% (1·3–7·1). Between-study heterogeneity was substantial for these estimates (I2 69–97%) with few explanations. However, subgroup analyses revealed that people in prison in low-income and middle-income countries had higher prevalences for depression (16·7% [95% CI 13·6–20·0]) than in high-income countries (10·8% [9·0–13·0]), and that, for people with psychosis who are incarcerated, psychiatrists were less likely to diagnose (3·5% [2·8–4·3]) than were non-psychiatrists (4·7% [3·9–5·5]).InterpretationOur study indicates that the prevalence of severe mental illness in people who are incarcerated worldwide is considerable. Meeting the treatment needs of people in prison who have mental ill health remains an ongoing challenge for public mental health. More evidence on how to improve the assessment, treatment, and linkage to services on release, which will require more research-friendly prison services, is now needed.FundingNone.
Early antiviral treatment with tenofovir alafenamide to prevent serious clinical adverse events in adults with chronic hepatitis B and moderate or high viraemia (ATTENTION): interim results from a randomised controlled trial
Authors: Young-Suk Lim, Ming-Lung Yu, Jonggi Choi, Chi-Yi Chen, Won-Mook Choi, Wonseok Kang, Gi-Ae Kim, Hyung Joon Kim, Yun Bin Lee, Jeong-Hoon Lee, Neung Hwa Park, So Young Kwon, Soo Young Park, Ji Hoon Kim, Gwang Hyeon Choi, Eun Sun Jang, Chien-Hung Chen, Yao-Chun Hsu, Ming-Jong Bair, Pin-Nan Cheng, Hung-Da Tung, Te-Sheng Chang, Ching-Chu Lo, Kuo-chih Tseng, Sheng-Shun Yang, Cheng-Yuan Peng, Seungbong Han
Journal: The Lancet. Gastroenterology & hepatology (2025)
The adverse public health effects of non-medical cannabis legalisation in Canada and the USA
Authors: Tesfa Mekonen Yimer, Eva Hoch, Benedikt Fischer, Danielle Dawson, Wayne Hall
Journal: The Lancet Public Health (2025)

SummaryCannabis consumption is legally prohibited in most countries in the world. Several countries are legalising cannabis for adult consumption. It is important to monitor the public health effects of these policy changes. In this paper, we summarise the evidence to date on the legalisation of adult non-medical cannabis use in Canada and the USA. We describe regulatory models for cannabis legalisation, changes in cannabis products and pricing, effects on the illicit cannabis market, changes in cannabis use, and changes in cannabis-related physical and mental health harms. We discuss the challenges in assessing the effects of cannabis legalisation on public health outcomes and emphasise the importance of continuous and rigorous monitoring of adverse health effects to inform the design of public health policies and regulations.
Hierarchical Protein Nano-crystalline Hydrogel with Extracellular Vesicles for Ectopic Lymphoid Structure Formation
Authors: Wonkyung Ahn, Jihoon Han, Nayeon Kim, Yeong Ha Hwang, Wonjun Kim, Yeram Lee, Dong Yun Lee, In Woo Cheong, Koohee Han, Gi-Hoon Nam, In-San Kim, Eun Jung Lee
Journal: Biomaterials (2025)
Unravelling the complex pathogenesis of hidradenitis suppurativa
Authors: John W Frew
Journal: British Journal of Dermatology (2025)

Hidradenitis suppurativa (HS) is a complex inflammatory disease, with rapid advances being made in our understanding of the complex immunological pathogenesis of the condition. New insights into the genomic landscape of HS have identified a number of genes that contribute to the development of HS in a polygenic manner, contributing to inflammatory dysregulation and alterations in epidermal stem cell fate in the follicular unit. These genomic variations can explain unique aspects of the disease such as the development and presence of epithelialized tunnels and abnormalities in wound healing. From genetic and translational studies, it is likely that these genetic alterations predispose to an innate immune dysregulation that can be triggered through sex hormone-responsive transcription factors with hormonal changes such as puberty, pregnancy and the menstrual cycle. The role of sex hormones in HS also has direct effects upon the development and maturation of inflammatory cells such as monocytes, which has the potential to explain differential patient response to treatments such as interleukin-23 antagonism. The role of adipose tissue as an active immunological organ also plays a role in the immune dysregulation seen in the disease. Fibrotic tissue and immunologically active fibroblasts play a significant role in the perpetuation of inflammation and development of adaptive immune dysfunction in the disease. The cutaneous and gut microbiomes play significant roles in the activation of innate immunity, although conflicting data exist as to their central or peripheral role in disease pathogenesis. Overall, our understanding of disease pathogenesis in HS is moving toward a more nuanced, complex paradigm in which patient heterogeneity in presentation and immunological characteristics are moving closer to the identification of therapeutic biomarkers to guide therapeutic modalities in the management of this burdensome condition.
Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD
Authors: Shaowei Wang, Boyang Li, Jie Li, Zhiheng Cai, Cristelle Hugo, Yi Sun, Lu Qian, Julia TCW, Helena C. Chui, Dante Dikeman, Isaac Asante, Stan G. Louie, David A. Bennett, Zoe Arvanitakis, Alan T. Remaley, Bilal E. Kerman, Hussein N. Yassine
Journal: Molecular Neurodegeneration (2025)

Abstract Background Cellular senescence, a hallmark of aging, has been implicated in Alzheimer’s disease (AD) pathogenesis. Cholesterol accumulation is known to drive cellular senescence; however, its underlying mechanisms are not fully understood. ATP-binding cassette transporter A1 (ABCA1) plays an important role in cholesterol homeostasis, and its expression and trafficking are altered in APOE4 and AD models. However, the role of ABCA1 trafficking in cellular senescence associated with APOE4 and AD remains unclear. Methods We examined the association between cellular senescence and ABCA1 expression in human postmortem brain samples using transcriptomic, histological, and biochemical analyses. Unbiased proteomic screening was performed to identify the proteins that mediate cellular ABCA1 trafficking. We created ABCA1 knock out cell lines and mouse models to validate the role of ABCA1 in cholesterol-induced mTORC1 activation and senescence. Additionally, we used APOE4-TR mice and induced pluripotent stem cell (iPSC) models to explore cholesterol-ABCA1-senescence pathways. Results Transcriptomic profiling of the human dorsolateral prefrontal cortex from the Religious Order Study/Memory Aging Project (ROSMAP) cohort revealed the upregulation of cellular senescence transcriptome signatures in AD, which correlated with ABCA1 expression and oxysterol levels. Immunofluorescence and immunoblotting analyses confirmed increased lipofuscin-stained lipids and ABCA1 expression in AD brains and an association with mTOR phosphorylation. Discovery proteomics identified caveolin-1, a sensor of cellular cholesterol accumulation, as a key promoter of ABCA1 endolysosomal trafficking. Greater caveolin-1 expression was observed in APOE4-TR mouse models and AD human brains. Oxysterol induced mTORC1 activation and senescence were regulated by ABCA1 lysosomal trapping. Treatment of APOE4-TR mice with cyclodextrin reduced brain oxysterol levels, ABCA1 lysosome trapping, mTORC1 activation, and attenuated senescence and neuroinflammation markers. In human iPSC-derived astrocytes, the reduction of cholesterol by cyclodextrin attenuated inflammatory responses. Conclusions Oxysterol accumulation in APOE4 and AD induced ABCA1 and caveolin-1 expression, contributing to lysosomal dysfunction and increased cellular senescence markers. This study provides novel insights into how cholesterol metabolism accelerates features of brain cellular senescence pathway and identifies therapeutic targets to mitigate these processes.
Gene editing of CD3 epsilon gene to redirect regulatory T cells for adoptive T cell transfer
Authors: Weijie Du, Fatih Noyan, Oliver McCallion, Vanessa Drosdek, Jonas Kath, Viktor Glaser, Carla Fuster-Garcia, Mingxing Yang, Maik Stein, Clemens Franke, Yaolin Pu, Olaf Weber, Julia K Polansky, Toni Cathomen, Elmar Jaeckel, Joanna Hester, Fadi Issa, Hans-Dieter Volk, Michael Schmueck-Henneresse, Petra Reinke, Dimitrios L Wagner
Journal: Molecular Therapy (2025)

Adoptive transfer of antigen-specific regulatory T cells (Tregs) is a promising strategy to combat immunopathologies in transplantation and autoimmune diseases. However, their low frequency in peripheral blood poses challenges for both manufacturing and clinical application. Chimeric antigen receptors (CARs) have been used to redirect the specificity of Tregs, employing retroviral vectors. However, retroviral gene transfer is costly, time consuming, and raises safety issues. Here, we explored non-viral CRISPR-Cas12a gene editing to redirect Tregs, using HLA-A2-specific constructs for proof-of-concept studies in transplantation models. Knock-in of an antigen-binding domain into the N terminus of CD3 epsilon (CD3ε) gene generates Tregs expressing a chimeric CD3ε-T cell receptor fusion construct (TRuC) protein which integrates into the endogenous TCR/CD3 complex. These CD3ε-TRuC Tregs exhibit potent antigen-dependent activation while maintaining responsiveness to TCR/CD3 stimulation. This enables preferential enrichment of TRuC-redirected Tregs over CD3ε KO Tregs via repetitive CD3/CD28-stimulation in a GMP-compatible expansion system. CD3ε-TRuC Tregs retained their phenotypic, epigenetic, and functional identity. In a humanized mouse model, HLA-A2-specific CD3ε-TRuC Tregs demonstrate superior protection of allogeneic HLA-A2+ skin grafts from rejection compared to polyclonal Tregs. This approach provides a pathway for developing clinical-grade CD3ε-TRuC-based Treg cell products for transplantation immunotherapy and other immunopathologies.
Corrigendum to “An update of isoprostanoid nomenclature” [Progress in Lipid Research 96 (2024) 101301–101310]
Authors: Camille Oger, Tereza Pavlíčková, Valérie Bultel-Poncé, Alexandre Guy, Jean-Marie Galano, Ullrich Jahn, Thierry Durand
Journal: Progress in Lipid Research (2025)
Implementation of a Cellular Automaton for efficient simulations of atrial arrhythmias
Authors: Giada S Romitti, Alejandro Liberos, María Termenón-Rivas, Javier Barrios-Álvarez de Arcaya, Dolors Serra, Pau Romero, David Calvo, Miguel Lozano, Ignacio García-Fernández, Rafael Sebastian, Miguel Rodrigo
Journal: Medical Image Analysis (2025)
Ibrutinib plus venetoclax in relapsed or refractory mantle cell lymphoma (SYMPATICO): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study
Authors: Michael Wang, Wojciech Jurczak, Marek Trneny, David Belada, Tomasz Wrobel, Nilanjan Ghosh, Mary-Margaret Keating, Tom van Meerten, Ruben Fernandez Alvarez, Gottfried von Keudell, Catherine Thieblemont, Frederic Peyrade, Marc Andre, Marc Hoffmann, Edith Szafer-Glusman, Jennifer Lin, James P Dean, Jutta K Neuenburg, Constantine S Tam
Journal: The Lancet Oncology (2025)
Management of immune checkpoint inhibitor-associated toxicities in older adults with cancer: recommendations from the International Society of Geriatric Oncology (SIOG)
Authors: Colm Mac Eochagain, Nina Rosa Neuendorff, Karolina Gente, Jan Leipe, Marthe Verhaert, Christine Sam, Nienke de Glas, Sindhuja Kadambi, Beverly Canin, Fabio Gomes, Lore Decoster, Beatriz Korc-Grodzicki, Siri Rostoft, Nicolò Matteo Luca Battisti, Hans Wildiers
Journal: The Lancet Oncology (2025)
Targeting the TRIM21-PD-1 axis potentiates immune checkpoint blockade and CAR T cell therapy
Authors: Jie Shi, Zijian Zhang, Hsin-Yi Chen, Yingmeng Yao, Shanwen Ke, Kechun Yu, Jiangzhou Shi, Xiangling Xiao, Chuan He, Bolin Xiang, Yishuang Sun, Minling Gao, Xixin Xing, Haisheng Yu, Xiyong Wang, Wei-Chien Yuan, Bugi Ratno Budiarto, Shih-Yu Chen, Tongcun Zhang, Yu-Ru Lee, Haichuan Zhu, Jinfang Zhang
Journal: Molecular Therapy (2025)
Extended Risankizumab Treatment in Patients With Crohn’s Disease Who Did Not Achieve Clinical Response to Induction Treatment
Authors: Remo Panaccione, Marc Ferrante, Iris Dotan, Julian Panés, Tadakazu Hisamatsu, Peter Bossuyt, Silvio Danese, Alexandra Song, Jasmina Kalabic, Namita Joshi, Javier Zambrano, Yafei Zhang, W Rachel Duan, Kristina Kligys, Marla C Dubinsky, James O Lindsay, Severine Vermeire, Britta Siegmund, Peter M Irving, Geert D'Haens
Journal: Clinical Gastroenterology and Hepatology (2025)

The efficacy and safety of extended treatment with risankizumab (RZB), an anti-interleukin-23 p19 monoclonal antibody, were evaluated in patients with moderate to severe Crohn's disease (CD) who did not achieve clinical response to 12 weeks (W) RZB induction treatment ('initial nonresponders'). Initial nonresponders to intravenous (IV) RZB induction (600mg or 1200mg at W0, W4, and W8) were rerandomized 1:1:1 to receive extended blinded RZB treatment (1200mg IV at W12, W16, and W20, or subcutaneous [SC] 180mg or 360mg at W12 and W20). Patients with clinical response to SC RZB at W24 ('delayed responders') continued their dose in FORTIFY. Clinical, endoscopic, and safety outcomes were evaluated. Most initial nonresponders achieved SF/APS clinical response by W24 (76.2% [180mg SC], 63.7% [360mg SC], 62.3% [1200mg IV]), while a subset also achieved W24 SF/APS clinical remission (43.0%, 45.1%, 22.1%), endoscopic response (32.4%, 32.5%, 40.5%), and endoscopic remission (25.1%, 18.0%, 23.5%). Most delayed responders to SC RZB continued to demonstrate clinical response at FORTIFY W52 (56.7% [180mg SC], 69.7% [360mg SC]), along with SF/APS clinical remission (43.3%, 54.5%), endoscopic response (36.7%, 45.5%), and endoscopic remission (40.0%, 42.4%). Numerically greater efficacy was generally observed with 360mg SC vs 180mg SC. The safety profile of extended treatment was consistent with previously reported trials. Most initial nonresponders to IV RZB induction who received 12W of extended RZB treatment demonstrated improved clinical and endoscopic outcomes at W24. Improvements in patients who received SC RZB extended treatment were maintained during FORTIFY. Extended treatment was well tolerated with no new safety risks identified.
Facilitating transpancreatic biliary sphincterotomy with a rotatable sphincterotome: a case of improved biliary cannulation
Authors: Tatsunori Satoh, Kodai Baba, Shinya Kawaguchi, Haruna Takahashi, Shinya Endo, Naofumi Shirane, Kazuya Ohno
Journal: Endoscopy (2025)

To perform endoscopic retrograde cholangiopancreatography (ERCP), cannulation of the common bile duct through the major papilla is necessary. However, even experts fail to achieve selective biliary cannulation in 5% to 20% of cases [1]. When standard cannulation techniques fail, precut incision methods such as needle-knife sphincterotomy and transpancreatic biliary sphincterotomy (TPBS) can be employed. However, these precut techniques also have failure rates of 10% to 40% [2]. Needle-knife sphincterotomy allows for flexible incision lines but is technically challenging, while TPBS is easier but limited by a fixed incision line and difficulty aligning with the bile duct axis. The new rotatable sphincterotome may overcome these limitations, making TPBS easier and more efficient. We herein report a case of successful selective biliary cannulation via TPBS using a novel sphincterotome (ENGETSU; Kaneka Medical, Osaka, Japan).
FKBP5 Inhibition Ameliorates Neurodegeneration and Motor Dysfunction in the Neuromelanin-SNCA Mouse Model of Parkinson’s Disease
Authors: Marta Garcia-Gomara, Naroa Legarra-Marcos, Maria Serena, Elvira Rojas-de-Miguel, Maria Espelosin, Irene Marcilla, Alberto Perez-Mediavilla, Maria Rosario Luquin, Jose Luis Lanciego, Maria Angeles Burrell, Mar Cuadrado-Tejedor, Ana Garcia-Osta
Journal: Molecular Therapy (2025)
Isatuximab, bortezomib, lenalidomide, and limited dexamethasone in patients with transplant-ineligible multiple myeloma (REST): a multicentre, single-arm, phase 2 trial
Authors: Frida Bugge Askeland, Einar Haukås, Tobias S Slørdahl, Anja Klostergaard, Tatjana Alexandersen, Anna Lysén, Pegah Abdollahi, Lene Kongsgaard Nielsen, Emil Hermansen, Fredrik Schjesvold
Journal: The Lancet Haematology (2025)
Diagnosis and treatment of Burkitt lymphoma in adults: clinical practice guidelines from ERN-EuroBloodNet
Authors: Vincent Ribrag, Dominique Bron, Grzegorz Rymkiewicz, Dieter Hoelzer, Judit Jørgensen, Aythami de Armas-Castellano, Maria Trujillo-Martín, Pierre Fenaux, Luca Malcovati, Natacha Bolaños, Josep-Maria Ribera, Charles Herbaux, Clémentine Sarkozy, Pier Luigi Zinzani, Jan Walewski, Martine E D Chamuleau
Journal: The Lancet Haematology (2025)
The Deubiquitinase USP28 Maintains the Expression of PPARγ and Its Inactivation Protects Mice from Diet-Induced MASH and Hepatocarcinoma
Authors: Changzhou Cai, Hangqi Luo, Jin Peng, Xinghua Zhen, Xiang Shen, Xiaomei Xi, Jianrong Zhu, Yanfei Fang, Xiaoli Chen, Jiewei Wang, Chaohui Yu, Pumin Zhang, Chengfu Xu
Journal: Molecular Therapy (2025)
Common Sense Oncology principles for the design, analysis, and reporting of phase 3 randomised clinical trials
Authors: Bishal Gyawali, Elizabeth A Eisenhauer, Winette van der Graaf, Christopher M Booth, Nathan I Cherny, Aaron M Goodman, Rachel Koven, Madeline L Pe, Bernard L Marini, Ghulam Rehman Mohyuddin, Gregory R Pond, Manju Sengar, Enrique Soto-Perez-de-Celis, Dario Trapani, Michelle Tregear, Brooke E Wilson, Ian F Tannock
Journal: The Lancet Oncology (2025)
Rucaparib versus chemotherapy for treatment of relapsed ovarian cancer with deleterious BRCA1 or BRCA2 mutation (ARIEL4): final results of an international, open-label, randomised, phase 3 trial
Authors: Amit M Oza, Alla Lisyanskaya, Alexander Fedenko, Andreia Cristina de Melo, Yaroslav Shparyk, Irina Rakhmatullina, Igor Bondarenko, Nicoletta Colombo, Valentyn Svintsitskiy, Luciano Biela, Marina Nechaeva, Domenica Lorusso, Giovanni Scambia, David Cibula, Róbert Póka, Ana Oaknin, Tamar Safra, Beata Mackowiak-Matejczyk, Ling Ma, Daleen Thomas, Kevin K Lin, Karen McLachlan, Sandra Goble, Rebecca Kristeleit
Journal: The Lancet Oncology (2025)
Aficamten vs Metoprolol for Obstructive Hypertrophic Cardiomyopathy
Authors: Pablo Garcia-Pavia, Ozlem Bilen, Melissa Burroughs, Juan Pablo Costabel, Edileide de Barros Correia, Anne M Dybro, Perry Elliott, Neal K Lakdawala, Amy Mann, Ajith Nair, Michael E Nassif, Steen H Poulsen, Patricia Reant, P Christian Schulze, Andrew Wang, Indrias Berhane, Stephen B Heitner, Daniel L Jacoby, Stuart Kupfer, Fady I Malik, Lisa Meng, Regina Sohn, Amy Wohltman, Michael A Fifer
Journal: JACC Heart Failure (2025)

Beta-blockers and nondihydropyridine calcium-channel blockers have been standard-of-care (SOC) medications for patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM), even though these agents do not directly affect the underlying pathophysiology of the disease. Cardiac myosin inhibitors act by decreasing the number of myosin heads binding to actin, reducing the pathologic hypercontractility of HCM, and have been shown to improve exercise capacity and alleviate symptoms in oHCM when added to SOC medications. Cardiac myosin inhibitors are currently considered as second-line therapy in the absence of head-to-head comparison studies vs SOC medications. The aim of the ongoing phase 3 study MAPLE-HCM (Metoprolol vs Aficamten in Patients With LVOT Obstruction on Exercise Capacity in HCM) is to fill this evidence gap by evaluating aficamten as both first-line therapy for newly diagnosed oHCM and as a monotherapy alternative for patients currently on SOC drugs. The authors describe the rationale, design, and baseline characteristics of patients in this study. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM [MAPLE-HCM]; NCT05767346).