tbuckley/cabot-search huggingface dataset:
Understanding contraceptive switching rationales from real world clinical notes using large language models
Authors: Brenda Y Miao, Christopher Y K Williams, Ebenezer Chinedu-Eneh, Travis Zack, Emily Alsentzer, Atul J Butte, Irene Y Chen
Journal: npj Digital Medicine (2025)

Abstract Understanding reasons for treatment switching is of significant medical interest, but these factors are often only found in unstructured clinical notes and can be difficult to extract. We evaluated the zero-shot abilities of GPT-4 and eight other open-source large language models (LLMs) to extract contraceptive switching information from 1964 clinical notes derived from the UCSF Information Commons dataset. GPT-4 extracted the contraceptives started and stopped at each switch with microF1 scores of 0.85 and 0.88, respectively, compared to 0.81 and 0.88 for the best open-source model. When evaluated by clinical experts, GPT-4 extracted reasons for switching with an accuracy of 91.4% (2.2% hallucination rate). Transformer-based topic modeling identified patient preference, adverse events, and insurance coverage as key reasons. These findings demonstrate the value of LLMs in identifying complex treatment factors and provide insights into reasons for contraceptive switching in real-world settings.
Top ten research priorities in global burns care: findings from the James Lind Alliance Global Burns Research Priority Setting Partnership
Authors: Hollie Sarah Richards, Robert M T Staruch, Suzannah Kinsella, Jelena Savovic, Riaz Qureshi, Daisy Elliott, Leila Rooshenas, Anni King, Amy Acton, Jonathan Bayuo, Simon Booth, Shobha Chamania, Le Quoc Chieu, Charlotte Coates, Declan Collins, Lise Deguire, Baljit Dheansa, Roy Dudley-Southern, Ian Easton, Dale Edgar, Janine Evans, Sian Falder, Emilio Gonzalez, Alex Holley, Catrina Holley, Ivette L Icaza, Claire Jowett, Jane Leaver, Alice Lee, Niall Martin, Jill Meirte, Nguyen Nh Lam, Catrin Pugh, Mamta Shah, Krissie Stiles, Marielle Vehmeijer, Tanveer Ahmed, Nikki Allorto, Murat Ali Cinar, Lewis Allen Dingle, Orlando Flores, Vincent Gabriel, Dhruv Ghosh, Jotham Gondwe, Teruichi Harada, Jagnoor Jagnoor, Vikash Ranjan Keshri, Goaxing Luo, Andrea Mc Kittrick, Natalie Meyers, Pinki Pargal, Carisa Parrish, Marie-Claude Pelchat, Mohsen Rezaeian, Edrisa Sanyang, Atul Suroy, Khaled Taibi, Leila Ait Abderrahim, Luiz Philipe Molina Vana, Katie Wang, Nukhba Zia, Jane M Blazeby, Amber Young
Journal: The Lancet Global Health (2025)
Longitudinal Evaluation of Clear-cell Renal Cell Carcinoma in von Hippel-Lindau Disease
Authors: W Marston Linehan, Cathy Anne Pinto, Yanfang Liu, Kristin Choo, Rabindra Gautam, Claire Fox, Ananya Roy, Mengying Li, Rafia Bosan, Deborah Nielsen, Beth Ryan, Zoe Blake, Krista Reynolds, Alexis Rompre-Brodeur, Peter A Pinto, Cathy Vocke, Sandeep Gurram, Mark W Ball, Rodolfo Perini, Ramaprasad Srinivasan
Journal: European Urology (2025)
Efficacy of Baloxavir Treatment in Preventing Transmission of Influenza
Authors: Arnold S. Monto, Klaus Kuhlbusch, Corrado Bernasconi, Bin Cao, Herman Avner Cohen, Emily Graham, Aeron C. Hurt, Laurie Katugampola, Takashi Kamezawa, Adam S. Lauring, Barry McLean, Takahiro Takazono, Andreas Widmer, Steffen Wildum, Benjamin J. Cowling
Journal: New England Journal of Medicine (2025)

Baloxavir marboxil (baloxavir) rapidly reduces influenza virus shedding, which suggests that it may reduce transmission. Studies of treatment with neuraminidase inhibitors have not shown sufficient evidence that they prevent transmission to contacts. We conducted a multicountry, phase 3b trial to assess the efficacy of single-dose baloxavir treatment to reduce influenza transmission from index patients to household contacts. Influenza-positive index patients 5 to 64 years of age were randomly assigned in a 1:1 ratio to receive baloxavir or placebo within 48 hours after symptom onset. The primary end point was transmission of influenza virus from an index patient to a household contact by day 5. The first secondary end point was transmission of influenza virus by day 5 that resulted in symptoms. Overall, 1457 index patients and 2681 household contacts were enrolled across the 2019-2024 influenza seasons; 726 index patients were assigned to the baloxavir group, and 731 to the placebo group. By day 5, transmission of laboratory-confirmed influenza was significantly lower with baloxavir than with placebo (adjusted incidence, 9.5% vs. 13.4%; adjusted odds ratio, 0.68; 95.38% confidence interval [CI], 0.50 to 0.93; P = 0.01), with an adjusted relative risk reduction of 29% (95.38% CI, 12 to 45). The adjusted incidence of transmission of influenza virus by day 5 that resulted in symptoms was 5.8% with baloxavir and 7.6% with placebo; however, the difference was not significant (adjusted odds ratio, 0.75; 95.38% CI, 0.50 to 1.12; P = 0.16). Emergence of drug-resistant viruses during the follow-up period occurred in 7.2% (95% CI, 4.1 to 11.6) of the index patients in the baloxavir group; no resistant viruses were detected in household contacts. No new safety signals were identified. Treatment with a single oral dose of baloxavir led to a lower incidence of transmission of influenza virus to close contacts than placebo. (Funded by F. Hoffmann-La Roche and others; CENTERSTONE ClinicalTrials.gov number, NCT03969212.).
Performance of Dialysis Facilities after Health-Equity Scoring Incentive
Authors: Kalli G. Koukounas, Meehir N. Dixit, Rebecca Thorsness, Rachel E. Patzer, Adam S. Wilk, Kelsey M. Drewry, Rajnish Mehrotra, Maricruz Rivera-Hernandez, David J. Meyers, Daeho Kim, Ankur D. Shah, Christopher H. Schmid, Amal N. Trivedi
Journal: New England Journal of Medicine (2025)
Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension
Authors: Luke J. Laffin, Branko Kopjar, Carrie Melgaard, Kathy Wolski, Jessica Ibbitson, Shivani Bhikam, Matthew R. Weir, Elizabeth O. Ofili, Reena Mehra, James M. Luther, Debbie L. Cohen, Ashish Sarraju, Michael J. Wilkinson, John M. Flack, David Rodman, Steven E. Nissen
Journal: New England Journal of Medicine (2025)

Aldosterone dysregulation contributes to hypertension. Lorundrostat is an aldosterone synthase inhibitor, but data on its efficacy and safety in patients with hypertension are limited. In this multicenter, double-blind, randomized, placebo-controlled trial, we assigned participants who were receiving two to five antihypertensive medications and had a blood-pressure measurement of 140/90 mm Hg or higher obtained during an office visit to undergo a standardized antihypertensive regimen for 3 weeks. Subsequently, participants with an average 24-hour ambulatory blood pressure of 130/80 mm Hg or higher were assigned to receive placebo, lorundrostat at a stable dose of 50 mg daily (the stable-dose group), or lorundrostat at a starting dose of 50 mg daily, with an increase to 100 mg daily if systolic blood pressure was 130 mm Hg or higher after 4 weeks (the dose-adjustment group). The primary end point was the change in 24-hour average systolic blood pressure from baseline to week 12, assessed as the least-squares mean difference from placebo (the placebo-adjusted change) in each lorundrostat group. A key secondary end point was the change in 24-hour average systolic blood pressure from baseline to week 4, assessed as the placebo-adjusted change in the combined lorundrostat groups. A total of 285 participants underwent randomization; 94 were assigned to the stable-dose group, 96 to the dose-adjustment group, and 95 to the placebo group. The mean age was 60 years, and 150 participants (53%) were Black. After 12 weeks, the least-squares mean change in 24-hour average systolic blood pressure was -15.4 mm Hg in the stable-dose group, -13.9 mm Hg in the dose-adjustment group, and -7.4 mm Hg in the placebo group. The placebo-adjusted change in blood pressure was -7.9 mm Hg (97.5% confidence interval [CI], -13.3 to -2.6) in the stable-dose group and -6.5 mm Hg (97.5% CI, -11.8 to -1.2) in the dose-adjustment group. The placebo-adjusted change in 24-hour average systolic blood pressure from baseline to week 4 in the combined lorundrostat groups was -5.3 mm Hg (95% CI, -8.4 to -2.3). A potassium level above 6.0 mmol per liter occurred in 5 participants (5%) in the stable-dose group, 7 participants (7%) in the dose-adjustment group, and no participants in the placebo group. Lorundrostat was associated with greater reductions in 24-hour average blood pressure than placebo in participants with uncontrolled and treatment-resistant hypertension. (Funded by Mineralys Therapeutics; Advance-HTN ClinicalTrials.gov number, NCT05769608.).
Tumor-Infiltrating Clonal Hematopoiesis
Authors: Oriol Pich, Elsa Bernard, Maria Zagorulya, Andrew Rowan, Constandina Pospori, Ramy Slama, Hector Huerga Encabo, Jennifer O’Sullivan, Despoina Papazoglou, Panayiotis Anastasiou, Chrysante S. Iliakis, Sally-Ann Clark, Krijn K. Dijkstra, Vittorio Barbè, Chris Bailey, Aaron J. Stonestrom, Katey S.S. Enfield, Mary Green, Charlotte K. Brierley, Alastair Magness, David R. Pearce, Robert E. Hynds, Rija Zaidi, Jayant K. Rane, Ángel F. Álvarez-Prado, Kerstin Thol, Rachel Scott, Supreet Kaur Bola, Elena Hoxha, Steve K. Harris, Karl S. Peggs, Sergio A. Quezada, Allan Hackshaw, Simone Zaccaria, Johanna A. Joyce, Ilaria Malanchi, Michael F. Berger, Mariam Jamal-Hanjani, Andreas Wack, Julian Downward, William Grey, Cristina Lo Celso, Eva Grönroos, Charles M. Rudin, Adam J. Mead, Dominique Bonnet, Elli Papaemmanuil, Charles Swanton
Journal: New England Journal of Medicine (2025)

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with increased mortality among patients with cancer. CHIP mutations with high variant-allele frequencies can be detected in tumors, a phenomenon we term tumor-infiltrating clonal hematopoiesis (TI-CH). The frequency of TI-CH and its effect on tumor evolution are unclear. We characterized CHIP and TI-CH in 421 patients with early-stage non-small-cell lung cancer (NSCLC) from the TRACERx study and in 49,351 patients from the MSK-IMPACT pan-cancer cohort. We studied the association of TI-CH with survival and disease recurrence and evaluated the functional effect of TET2-mutant CHIP on the biologic features of lung tumors. Among patients with NSCLC, 42% of those with CHIP had TI-CH. TI-CH independently predicted an increased risk of death or recurrence, with an adjusted hazard ratio of 1.80 (95% confidence interval [CI], 1.23 to 2.63) as compared with the absence of CHIP and an adjusted hazard ratio of 1.62 (95% CI, 1.02 to 2.56) as compared with CHIP in the absence of TI-CH. Among patients with solid tumors, 26% of those with CHIP had TI-CH. TI-CH conferred a risk of death from any cause that was 1.17 times (95% CI, 1.06 to 1.29) as high as the risk with CHIP in the absence of TI-CH. TET2 mutations were the strongest genetic predictor of TI-CH; such mutations enhanced monocyte migration to lung tumor cells, fueled a myeloid-rich tumor microenvironment in mice, and resulted in the promotion of tumor organoid growth. TI-CH increased the risk of disease recurrence or death among patients with NSCLC and the risk of death from any cause among patients with solid tumors. TI-CH remodeled the tumor immune microenvironment and accelerated tumor organoid growth, findings that support a role for an aging-related hematologic clonal proliferation in cancer evolution. (Funded by the Royal Society and others.).
Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis
Authors: James D. Chalmers, Pierre-Régis Burgel, Charles L. Daley, Anthony De Soyza, Charles S. Haworth, David Mauger, Michael R. Loebinger, Pamela J. McShane, Felix C. Ringshausen, Francesco Blasi, Michal Shteinberg, Kevin Mange, Ariel Teper, Carlos Fernandez, Migdalia Zambrano, Chunpeng Fan, Xiangmin Zhang, Mark L. Metersky
Journal: New England Journal of Medicine (2025)

In bronchiectasis, neutrophilic inflammation is associated with an increased risk of exacerbations and disease progression. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), targets neutrophil serine proteases, key mediators of neutrophilic inflammation. In a phase 3, double-blind trial, we randomly assigned patients with bronchiectasis (in a 1:1:1 ratio for adults and a 2:2:1 ratio for adolescents) to receive brensocatib (10 mg or 25 mg once per day) or placebo. The primary end point was the annualized rate of adjudicated pulmonary exacerbations over a 52-week period. The secondary end points, listed in hierarchical testing order, were the time to the first exacerbation during the 52-week period; the percentage of patients remaining exacerbation-free at week 52; the change in forced expiratory volume in 1 second (FEV1); the annualized rate of severe exacerbations; and change in quality of life. A total of 1721 patients (1680 adults and 41 adolescents) underwent randomization and received brensocatib or placebo. The annualized rate of pulmonary exacerbations was 1.02 in the 10-mg brensocatib group, 1.04 in the 25-mg brensocatib group, and 1.29 in the placebo group (rate ratio, brensocatib vs. placebo, 0.79 [95% confidence interval {CI}, 0.68 to 0.92; adjusted P = 0.004] with the 10-mg dose and 0.81 [95% CI, 0.69 to 0.94; adjusted P = 0.005] with the 25-mg dose). The hazard ratio for the time to the first exacerbation was 0.81 (95% CI, 0.70 to 0.95; adjusted P = 0.02) with the 10-mg dose and 0.83 (95% CI, 0.70 to 0.97; adjusted P = 0.04) with the 25-mg dose. In each brensocatib group, 48.5% of patients remained exacerbation-free at week 52, as compared with 40.3% in the placebo group (rate ratio, 1.20 [95% CI, 1.06 to 1.37; adjusted P = 0.02] with the 10-mg dose and 1.18 [95% CI, 1.04 to 1.34; adjusted P = 0.04] with the 25-mg dose). At week 52, FEV1 had declined by 50 ml with the 10-mg dose, 24 ml with the 25-mg dose, and 62 ml with placebo (least-squares mean difference vs. placebo, 11 ml [95% CI, -14 to 37; adjusted P = 0.38] with the 10-mg dose and 38 ml [95% CI, 11 to 65; adjusted P = 0.04] with the 25-mg dose). The incidence of adverse events was similar across groups, except for a higher incidence of hyperkeratosis with brensocatib. Among patients with bronchiectasis, once-daily treatment with brensocatib (10 mg or 25 mg) led to a lower annualized rate of pulmonary exacerbations than placebo, and the decline in FEV1 was less with the 25-mg dose of brensocatib than with placebo. (Funded by Insmed; ASPEN ClinicalTrials.gov number, NCT04594369; EudraCT number, 2020-003688-25.).
Engineering fibroblast with reprogramming and spheronization for bone defect repair
Authors: Yanjiao Li, Bin Jiang, Zhen Wu, Zhaoxia Ma, Lihua Qiu, Wen Cui, Yunhui Zhao, Jinghe Yan, Daiping Ma, Xingfei Wu, Shu Liang, Sitao Wang, Yanqun Zhao, Mengting Wang, Min Hu
Journal: Bioactive Materials (2025)
Effect of Intravenous Immunoglobulin (IVIG) Supplementation on infection-free survival in recipients of BCMA-directed bispecific antibody therapy for multiple myeloma
Authors: Meera Mohan, Aniko Szabo, Heloise Cheruvalath, Anna Clennon, Vineel Bhatlapenumarthi, Anannya Patwari, Metodi Balev, Divaya Bhutani, Asis Shrestha, Sharmilan Thanendrarajan, Binod Dhakal, Maurizio Zangari, Anup Trikannad, Sruthi Vellanki, Samer Al-Hadidi, Suzanne Lentzsch, Frits van Rhee, Aishee Bag, Anita D'Souza, Nishi Shah, Rajshekhar Chakraborty, Mansi R Shah, Carolina Schinke
Journal: Blood Cancer Journal (2025)
Errata: Randomized Comparison of Magnetic Resonance Imaging Versus Transurethral Resection for Staging New Bladder Cancers: Results From the Prospective BladderPath Trial
Authors: Richard T. Bryan, Wenyu Liu, Sarah J. Pirrie, Rashid Amir, Jean Gallagher, Shaista Hafeez, Ana I. Hughes, Kieran P. Jefferson, Allen Knight, Veronica Nanton, Harriet P. Mintz, Ann M. Pope, Jacob Cherian, Kingsley Ekwueme, Lyndon Gommersall, Giles Hellawell, Paul Hunter-Campbell, Gokul Kanda Swamy, Sanjeev Kotwal, Vivekanandan Kumar, David Mak, Amar Mohee, Thiagarajan Nambirajan, Douglas G. Ward, Steven J. Kennish, James W.F. Catto, Prashant Patel, Nicholas D. James
Journal: Journal of Clinical Oncology (2025)
Prognostic Time Frame of Plaque and Hemodynamic Characteristics and Integrative Risk Prediction for Acute Coronary Syndrome
Authors: Seokhun Yang, Jae Wook Jung, Sang-Hyeon Park, Jinlong Zhang, Keehwan Lee, Doyeon Hwang, Kyu-Sun Lee, Sang-Hoon Na, Joon-Hyung Doh, Chang-Wook Nam, Tae Hyun Kim, Eun-Seok Shin, Eun Ju Chun, Su-Yeon Choi, Hyun Kuk Kim, Young Joon Hong, Hun-Jun Park, Song-Yi Kim, Mirza Husic, Jess Lambrechtsen, Jesper M Jensen, Bjarne L Nørgaard, Daniele Andreini, Pal Maurovich-Horvat, Bela Merkely, Martin Penicka, Bernard de Bruyne, Abdul Ihdayhid, Brian Ko, Georgios Tzimas, Jonathon Leipsic, Javier Sanz, Mark G Rabbat, Farhan Katchi, Moneal Shah, Nobuhiro Tanaka, Ryo Nakazato, Taku Asano, Mitsuyasu Terashima, Hiroaki Takashima, Tetsuya Amano, Yoshihiro Sobue, Hitoshi Matsuo, Hiromasa Otake, Takashi Kubo, Masahiro Takahata, Takashi Akasaka, Teruhito Kido, Teruhito Mochizuki, Hiroyoshi Yokoi, Taichi Okonogi, Tomohiro Kawasaki, Koichi Nakao, Tomohiro Sakamoto, Taishi Yonetsu, Tsunekazu Kakuta, Yohei Yamauchi, Charles A Taylor, Jeroen J Bax, Leslee J Shaw, Peter H Stone, Jagat Narula, Bon-Kwon Koo
Journal: JACC. Cardiovascular imaging (2025)
Real-World Outcomes of SGLT2 Inhibitors in Very Elderly Patients With Heart Failure With Preserved Ejection Fraction
Authors: Abdelhakim Hacil, Yara Antakly-Hanon, Audrey Lacour, Jean-Philippe David, Tesnim Khalifa, Matthieu Piccoli, Aude Clemencin, Patrick Assayag, Jean-Sebastien Vidal, Olivier Hanon
Journal: JACC Heart Failure (2025)
Results of the Precision Event Monitoring for Patients With Heart Failure Using HeartLogic Study (PREEMPT-HF)
Authors: Andrew J Sauer, Craig M Stolen, Jonathan B Shute, Brian Kwan, Ramesh Wariar, Stephen B Ruble, Roy S Gardner, John P Boehmer
Journal: JACC Heart Failure (2025)

Improved patient monitoring and management after heart failure (HF) hospitalizations are needed to reduce readmissions significantly. The aim of this study was to investigate the association between monitoring data and readmissions. PREEMPT-HF (PRecision Event Monitoring for PatienTs with Heart Failure using HeartLogic) was a global, observational, single-arm study enrolling adult HF patients remotely monitored with HeartLogic-capable implantable cardioverter-defibrillator and cardiac resynchronization therapy devices. Patients and clinicians were blinded to the index and alerts. Participants were followed for 12 months for site reporting of events. A total of 2,155 patients were enrolled at 103 sites and were monitored remotely (39% implantable cardioverter-defibrillators and 61% cardiac resynchronization therapy-defibrillators). There were 243 hospitalizations for HF, of which 156 (64%) were index hospitalizations. There were 25 (28%) unplanned all-cause readmissions in the 30 days after discharge and 45 (46%) all-cause readmissions within 90 days. Alert sensitivity for outpatient visits and hospitalizations for HF was 78.3%, and the false-positive rate was 1.18/year. The HeartLogic index was higher before index hospitalizations for HF when followed by HF or readmission for all causes. Index hospitalizations for HF were also more likely to be followed by readmission for HF in 90 days if the patient was in an alert state (vs out-of-alert state) 1 or 2 weeks before or 2 weeks after the index admission. HeartLogic index trends were significantly different for patients who were readmitted for HF. These trends suggest that individuals at risk for readmission have had a more sustained worsening and/or insufficient intervention during the initial hospitalization for HF. (PRecision Event Monitoring for PatienTs with Heart Failure using HeartLogic [PREEMPT-HF]; NCT03579641).
Health Effects and Water Quality Following Low Pressure Events in Drinking Water Distribution Systems in the United States
Authors: Mia C. Mattioli, Katharine M. Benedict, Shanna Miko, Catherine E. Barrett, Alexis Roundtree, Sunkyung Kim, Sarah A. Collier, Elizabeth Adam, Julia W. Gargano, Jonathan S. Yoder, Deborah A. Vacs Renwick, Kenneth Rotert, Mike Sullivan, Sharon Sweeney, Michael Beach, Vincent R. Hill
Journal: Environmental Health Perspectives (2025)

Low pressure events (LPEs), defined as a water service disruption that presumably lowers system water pressure, can cause drinking water contamination resulting in increased illness risk to consumers. Examine whether LPEs increase the risk for highly credible acute gastrointestinal illness (HCGI) and acute respiratory illness (ARI) and compare water quality in exposed and unexposed areas in the United States. A matched cohort study was conducted during 2015-2019. For each LPE, household survey exposed areas were matched 1:2 with unexposed areas based on water main size and material at the point of repair, as well as the housing type and demographic characteristics of the local population from the most recent census tract. Water samples were collected to monitor physicochemical and microbiological water quality parameters. Households (HHs) were surveyed about water use and illness during the 2 weeks after the LPE. Multivariable log-binomial models clustered on utility and LPE number were used to investigate associations between LPE exposure and HCGI and ARI. Five water utilities reported 58 LPEs, including planned maintenance (76%) and emergency (24%) events. Controlling for livestock near home, private well presence, number of people in HH, and travel away from home, exposed HH were at higher risk of HCGI compared to unexposed HH (risk ratio =1.20; 95%CI: 1.05,1.37). No associations between LPE and ARI were detected. Certain LPEs characteristics like pipe material, size, and depth were associated with an increased HH HCGI risk. HHs experiencing LPEs where low disinfectant residual, high adenosine triphosphate, or general Bacteroidales were detected in water following an LPE repair were also at a higher risk for HCGI. LPEs were associated with 20% higher risk of HCGI in HHs. Planned improvements to water distribution system infrastructure, adherence to industry standard distribution repair practices, and water monitoring following pipe repairs could supplement community alert systems to reduce illnesses from LPEs. https://doi.org/10.1289/EHP15564.
WWP1–SHARP1–C/EBPβ positive feedback loop modulates development of metabolic dysfunction–associated steatotic liver disease
Authors: Hao Chen, Yuanxun Gong, Fei Wu, Man Wu, Shu Li, Bofeng Chen, Jie Wang, Min Qiu, Ying Xu, Wei Zhao, Tianxing Chen
Journal: Metabolism (2025)
Research models to study lewy body dementia
Authors: Suelen Lucio Boschen, Aarushi A Mukerjee, Ayman H Faroqi, Ben E Rabichow, John Fryer
Journal: Molecular Neurodegeneration (2025)

Abstract Lewy body dementia (LBD) encompasses neurodegenerative dementias characterized by cognitive fluctuations, visual hallucinations, and parkinsonism. Clinical differentiation of LBD from Alzheimer’s disease (AD) remains complex due to symptom overlap, yet approximately 25% of dementia cases are diagnosed as LBD postmortem, primarily identified by the presence of α-synuclein aggregates, tau tangles, and amyloid plaques. These pathological features position LBD as a comorbid condition of both Parkinson’s disease (PD) and AD, with over 50% of LBD cases exhibiting co-pathologies. LBD’s mixed pathology complicates the development of comprehensive models that reflect the full spectrum of LBD’s etiological, clinical, and pathological features. While existing animal and cellular models have facilitated significant discoveries in PD and AD research, they lack specificity in capturing LBD’s unique pathogenic mechanisms, limiting the exploration of therapeutic avenues for LBD specifically. This review assesses widely used PD and AD models in terms of their relevance to LBD, particularly focusing on their ability to replicate human disease pathology and assess treatment efficacy. Furthermore, we discuss potential modifications to these models to advance the understanding of LBD mechanisms and propose innovative research directions aimed at developing models with enhanced etiological, face, predictive, and construct validity.