tbuckley/cabot-search huggingface dataset:
CRISPR-Cas13d functional transcriptomics reveals widespread isoform-selective cancer dependencies on lncRNAs
Authors: Eugenio Morelli, Anil Aktas Samur, Domenico Maisano, Claire Gao, Vanessa Katia Favasuli, Dimitrios Papaioannou, Giovanni De Nola, Jonathan E Henninger, Na Liu, Marcello Turi, Pietro Folino, Laure Vreux, Michela Cumerlato, Liang Chen, Iannis Aifantis, Mariateresa Fulciniti, Kenneth C. Anderson, Abigail KR Lytton-Jean, Annamaria Gulla, Richard Young, Mehmet K. Samur, Nikhil C. Munshi
Journal: Blood (2025)

Long noncoding RNAs (lncRNAs) are a significant yet largely uncharted component of the cancer transcriptome, with their isoform-specific functions remaining poorly understood. In this study, we employed RNA-targeting CRISPR-Cas13d to uncover and characterize hundreds of tumor-essential (te)-lncRNA isoforms with clinical relevance. Focusing on multiple myeloma (MM), we targeted the lncRNA transcriptome expressed in tumor cells from MM patients and revealed both MM-specific and pan-cancer dependencies across diverse cancer cell lines, which we further validated in animal models. Additionally, we mapped the subcellular localization of these te-lncRNAs, identifying over 30 cytosolic isoforms that proved essential when targeted by cytosol-localized Cas13d. Notably, a specific isoform of SNHG6, enriched in the endoplasmic reticulum, interacts with heat shock proteins to maintain cellular proteostasis. We also integrated functional and clinical data into the publicly accessible LongDEP Portal, providing a valuable resource for the research community. Our study offers a comprehensive characterization of te-lncRNAs, underscoring their oncogenic roles and therapeutic potential.
Imaging Mass Cytometry Reveals the Order of Events in the Pathogenesis of Immune-Mediated Aplastic Anemia
Authors: Emma S. Pool, Sietse J. Luk, Marieke E. IJsselsteijn, Vincent van Unen, Noel F.C.C. de Miranda, J.H. Frederik Falkenburg, Frits Koning, Mirjam H.M. Heemskerk, Jennifer M-L. Tjon
Journal: Blood (2025)
Covert orienting: the dark matter of social attention
Authors: Tom Foulsham, Alan Kingstone
Journal: Trends in Cognitive Sciences (2025)

Covert visual attention is often seen as a lab phenomenon. Yet, in real-life, people routinely shift their attention to others without moving their eyes, a fact overlooked in most research. To truly understand natural behaviour, we must look beyond the eyes and illuminate this dark matter of social attention.
Evolving Risk of Urinary Adverse Events Across Localized Prostate Cancer Treatments: A Propensity-weighted Analysis of Surveillance, Epidemiology and End Results-Medicare Data
Authors: Kevin D Li, Marvin N Carlisle, Stephanie Jarosek, Hiren V Patel, Anna Faris, Sean P Elliott, Matthew R Cooperberg, Peter R Carroll, Benjamin N Breyer
Journal: European Urology (2025)

Prostate cancer treatments can cause long-term urinary adverse events (UAEs), but time-varying risks across treatments remain understudied. Using Surveillance, Epidemiology and End Results-Medicare data, we evaluated men aged ≥66 yr with localized prostate cancer treated with radical prostatectomy (RP), external beam radiotherapy (EBRT), brachytherapy (BT), EBRT + BT, RP + EBRT, or ablation between 2000 and 2017. The primary outcome was any UAE requiring a procedure, with follow-up from treatment initiation and censoring at disease progression. Kaplan-Meier analysis was used to estimate the UAE cumulative incidence and the propensity-weighted restricted mean survival time (RMST) to quantify mean UAE-free survival at 18 yr. The cohort included 166 581 patients: 40% received EBRT, 30% RP, 14% BT + EBRT, 12% BT, 3.1% RP + EBRT, and 1.7% ablation. Combined therapy carried the highest risk, with other modalities showing time-dependent changes. At 18 yr, the UAE risk was highest for RP + EBRT (41%), followed by BT + EBRT (35%), EBRT (29%), RP (23%), and BT (22%). Adjusted RMST to 18 yr was shortest for RP + EBRT (13.1 yr) and longest for BT (15.8 yr) and ablation (15.6 yr). In comparison to RP (15.1 yr), UAE-free survival was 2.0 yr shorter with RP + EBRT (RMST ratio 0.87; p < 0.001) and 0.2 yr shorter with EBRT + BT (RMST ratio 0.99; p < 0.001). The balance between oncologic efficacy and long-term urinary toxicity is key to treatment selection.
Spatial multiomics decipher fibroblast–macrophage dynamics in systemic sclerosis
Authors: Zhijian Li, Aleix Rius Rigau, Wenjie Xie, Linlin Huang, Wenjing Ye, Yi-Nan Li, Alexandru-Emil Matei, Christina Bergmann, Xiaohang Shao, Hejian Zou, Jiucun Wang, Luca Pinello, Jörg H W Distler, Rui He, Minrui Liang
Journal: Annals of the Rheumatic Diseases (2025)

Stromal-immune crosstalk shapes the pathogenic microenvironment of systemic sclerosis (SSc), but the spatial regulatory networks underlying fibrogenesis remain poorly defined. We aimed to explore tissue organisation and cell coordination in SSc skin, providing spatiotemporal insights into disease mechanisms and bridging the gap between omics discovery and precision medicine. We performed spatial transcriptomics on skin biopsies from 10 patients with diffuse cutaneous SSc and 4 healthy controls using the 10× Visium platform. These findings were confirmed using higher-resolution Stereo-seq transcriptomics, spatial proteomics, and single-cell RNA sequencing data from patients with SSc, SSc mouse models, and wound-healing reindeer models. In vivo and in vitro studies were conducted to validate the key regulatory pathways. Fourteen skin biopsies were analysed, revealing significant expansion of fibrotic niches enriched with fibroblasts and macrophages in SSc, correlating with clinical severity. We revealed disease-specific cell states of fibroblasts and macrophages and evaluated their spatial dependency and cell-cell communication. Stratification based on signature genes enabled the identification of patients with SSc with progressive disease and treatment-nonresponsive phenotype. ACKR3 (a CXCL12 decoy receptor) was selectively expressed in myofibroblast progenitors, which diminished during differentiation towards mature myofibroblast, potentially serving to regulate CXCL12/CXCR4-mediated proinflammatory macrophage recruitment. Inhibition of CXCR4 attenuated skin and lung fibrosis in experimental fibrosis mouse models. Our spatially resolved atlas uncovered dynamic fibroblast-macrophage interplay as a hallmark of fibrotic niche expansion. These findings offer spatiotemporal insights into disease mechanisms and pave the way for advanced mechanistic and therapeutic studies, bridging the gap between omics discovery and precision medicine.
In immune-mediated necrotising myopathy, anti-HMGCR antibodies inhibit HMGCR activity, leading to the sarcoplasmic accumulation of lipid droplets and myofibres necrosis
Authors: Margherita Giannini, Giulia Quiring, Mustapha Oulad-Abdelghani, Béatrice Lannes, Yves Allenbach, Olivier Benveniste, Olivier Boyer, Aleksandra Nadaj Pakleza, Bernard Geny, Alain Meyer
Journal: Annals of the Rheumatic Diseases (2025)
mTOR Inhibitors and Vaccine Response in Kidney Transplant Recipients
Authors: Griffith B. Perkins, Matthew J. Tunbridge, Cheng Sheng Chai, Christopher M. Hope, Arthur Eng Lip Yeow, Tania Salehi, Julian Singer, Bree Shi, Makutiro G. Masavuli, Zelalem Addis Mekonnen, Pablo Garcia-Valtanen, Svjetlana Kireta, Julie K. Johnston, Christopher J. Drogemuller, Beatrice Z. Sim, Shane M. Spencer, Benedetta C. Sallustio, Iain Comerford, George Bouras, Daniela Weiskopf, Alessandro Sette, Anupriya Aggarwal, Vanessa Milogiannakis, Anouschka Akerman, Stuart Turville, Plinio R. Hurtado, Tracey Ying, Pravin Hissaria, Simon C. Barry, Steven J. Chadban, Branka Grubor-Bauk, P. Toby Coates
Journal: Journal of the American Society of Nephrology (2025)

Background: Failure to develop protective immunity in response to vaccination is common among kidney transplant recipients, rendering them susceptible to severe infection. Novel strategies are required. Here, we investigated the potential of mechanistic-target-of-rapamycin (mTOR) inhibitors to improve vaccine responses. Methods: Humoral and cellular responses to primary COVID-19 vaccination (ChAdOx1 or BNT162b2) were assessed for kidney transplant recipients receiving mTOR inhibitor-based (mTOR inhibitor, mycophenolate, prednisolone, N=15) and standard-of-care (tacrolimus, mycophenolate, prednisolone, N=40) immunosuppression, and healthy cohabitants (N=71), in a prospective observational study. Findings were validated and mechanisms explored in mice. Low/non-responding kidney transplant recipients receiving standard-of-care immunosuppression (N=54) were then randomized 1:1 to switch from mycophenolate to sirolimus, or remain on standard-of-care, for 4 weeks prior to receiving COVID-19 booster vaccination. Augmentation of immunity to COVID-19 was assessed as the primary outcome measure. Results: A 12-fold greater IFNγ-T cell response to primary vaccination was observed in kidney transplant recipients receiving mTOR inhibitor-based versus standard-of-care immunosuppression (520 vs 43 spot-forming units/10 6 cells, p &lt; 0.001). A greater frequency of functional memory T cells in the mTOR inhibitor group was observed for both the CD4 + (0.20% vs. 0.05%, p &lt; 0.001) and CD8 + (0.35% vs. 0.07%, p = 0.006) compartments by flow cytometry, and kidney transplant recipients receiving mTOR inhibitor-based immunosuppression produced greater frequencies of SARS-CoV-2-specific CD4 + T cells than healthy cohabitants (1.17% vs 0.48%, p = 0.03). In mice, sirolimus treatment enhanced both recall and de novo T cell responses to homologous and Omicron-specific booster vaccines. Switch from mycophenolate to sirolimus was well tolerated, however no significant difference was observed in the proportion of kidney transplant recipients in the intervention and control arms that achieved protective virus neutralization (10/25 [40%] vs 9/21 [43%] respectively, p = 0.85), nor in T cell response to vaccination (p = 0.89). Conclusions: mTOR inhibition was associated with improved T cell memory formation in kidney transplant recipients, however this effect was not reproduced by a short-term mycophenolate to sirolimus switch strategy.
Observed and hidden factors underlying the accumulation of chronic diseases across eight major organ systems: a longitudinal birth cohort study
Authors: Markus J Haapanen, Jenni Niku, Tuija M Mikkola, Davide L Vetrano, Amaia Calderón-Larrañaga, Serhiy Dekhtyar, Eero Kajantie, Mikaela B von Bonsdorff, Johan G Eriksson
Journal: The Lancet Healthy Longevity (2025)
Association between physical activity and sedentary behaviour and changes in intrinsic capacity in Spanish older adults (Seniors-ENRICA-2): a prospective population-based study
Authors: Juan Luis Sánchez-Sánchez, Rosario Ortolá, Jose R Banegas, Alejandro Lucia, Fernando Rodríguez-Artalejo, Mercedes Sotos-Prieto, Pedro L Valenzuela
Journal: The Lancet Healthy Longevity (2025)
Effect of assigned sex on the age at which individuals seek specialist gender affirming care
Authors: Freya K. Kahn, Chantal M. Wiepjes, David Colon-Cabrera, Michelle A. Tollit, Monsurul Hoq, Debi Feldman, Anja Ravine, Riki Lane, Thomas D. Steensma, Kenneth C. Pang
Journal: International Journal of Transgender Health (2025)
British Thoracic Society Clinical Statement on<i>Aspergillus</i>-related chronic lung disease
Authors: Jeremy Stuart Brown, Darius Armstrong-James, Jonathan Ayling-Smith, Matthijs Backx, Meg Coleman, David Connell, Paddy Dennison, Damian G Downey, Fiona Lynch, Wei Shen Lim, Jenny White, Caroline Baxter
Journal: Thorax (2025)
A phase II basket trial of dual anti‐CTLA‐4 and anti‐PD‐1 blockade in rare tumors (DART) SWOG S1609: durable responses and delayed pseudoprogression in small cell carcinoma of the ovary, hypercalcemic type cohort
Authors: Young Kwang Chae, Megan Othus, Sandip Pravin Patel, Raid Aljumaily, Khine Z. Win, Tanya Pejovic, Sajeve S. Thomas, William R. Robinson, Hye Sung Kim, Liam Il‐Young Chung, Christine M. McLeod, Helen X. Chen, Elad Sharon, Howard Streicher, Christopher W. Ryan, Charles D. Blanke, Razelle Kurzrock
Journal: Cancer Communications (2025)

Abstract Background The combined use of anti‐programmed cell death protein 1 ( PD‐1 )/anti‐cytotoxic T‐lymphocyte associated protein 4 ( CTLA‐4) checkpoint inhibitors has been effective in various cancer types. The Southwest Oncology Group (SWOG) Dual Anti‐ CTLA‐4 and Anti‐ PD‐1 Blockade in Rare Tumors (DART) S1609 study investigated ipilimumab and nivolumab in ultra‐rare cancers, including small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). The purpose of the study was to evaluate the potential clinical benefit of ipilimumab and nivolumab in patients with SCCOHT. Methods DART was a prospective, open‐labeled, multicenter (&gt;1,000 US sites), multi‐cohort phase II clinical trial of intravenous administration of ipilimumab (1 mg/kg, every 6 weeks) plus nivolumab (240 mg, every 2 weeks). The primary endpoint was overall response rate [ORR, confirmed complete response (CR) and partial response (PR)] per RECIST. Secondary endpoints included progression‐free survival (PFS), overall survival (OS), clinical benefit rate (CBR; overall response plus stable disease ≥6 months), and toxicity. Immune responses were also evaluated. Results Six patients (median age, 30.5 years; median, 2 prior therapies; no prior immunotherapy exposure) with advanced/metastatic SCCOHT were evaluable. ORR and CBR were both 16.7% (1/6) with one patient having a confirmed CR lasting 46.2+ months. However, another patient had a confirmed immune CR (iCR) with immune PFS (iPFS) of 53+ months [ORR/iORR, 33.3% (2/6)]. Notably, the latter patient had a progressing lesion at 24 weeks after initial response, but with renewed regression with ongoing therapy, suggesting delayed pseudo‐progression. At 12‐months, 3 patients remained alive. Median PFS was 1.4 months (range, 0.9 months‐not reached); median OS was 14.2 months (2 months‐not reached). No adverse events caused treatment discontinuation. Conclusion Two of 6 patients (33.3%) with SCCOHT achieved durable CR/iCR and long‐term survival with ipilimumab plus nivolumab. Correlative studies to determine response and resistance markers are ongoing. Clinicaltrials.Gov Registry NCT02834013
Correction: Determining optimal timing of birth for women with chronic or gestational hypertension at term: The WILL (When to Induce Labour to Limit risk in pregnancy hypertension) randomised trial
Authors: Laura A. Magee, Katie Kirkham, Sue Tohill, Eleni Gkini, Catherine A. Moakes, Jon Dorling, Marcus Green, Jennifer A. Hutcheon, Mishal Javed, Jesse Kigozi, Ben W. M. Mol, Joel Singer, Pollyanna Hardy, Clive Stubbs, James G. Thornton, Peter von Dadelszen
Journal: PLoS Medicine (2025)

[This corrects the article DOI: 10.1371/journal.pmed.1004481.].
Organoid technologies in antitumor drug screening: past development, present applications, and future prospects
Authors: Junfa Yang, Yipin Yang, Pengkai Xu, Yong Yao, Heng Tian, Xinyi Wang, Hui Fang, Shangqing Ge, Yan Yao, Yafen Wang, Lin Hu, Bangjie Chen, Tao Xu
Journal: International Journal of Surgery (2025)
Sequential combinations of rapid immunoassays for prompt recognition of heparin-induced thrombocytopenia
Authors: Thomas Steinauer, Elena Matthey-Guirao, Francisco Javier Gomez, Luana Rittener-Ruf, Matteo Marchetti, Matthew Goodyer, Mitja Nabergoj, Stefano Barelli, Francesco Grandoni, Maxime Grégoire Zermatten, Lorenzo Alberio
Journal: Blood (2025)
Impact of obesity on postoperative complications in colorectal cancer surgery: A systematic review and meta-analysis
Authors: Gerardo Sarno, Daniel Simancas-Racines, Antonio Gargiulo, Anna Tedesco, Biancamaria Iacone, Claudia Reytor-González, Juan Marcos Parise-Vasco, Jaime Angamarca Iguago, Sabrina Sarno, Evelyn Frias-Toral, Umberto Bracale
Journal: Seminars in Cancer Biology (2025)
Myeloid cell genome-wide screen identifies variants associated with Mycobacterium tuberculosis-induced cytokine transcriptional responses
Authors: Joshua J Ivie, Kimberly A Dill-McFarland, Jason D Simmons, Glenna J Peterson, Penelope H Benchek, Harriet Mayanja-Kizza, Lily E Veith, Moeko Agata, Dang Tm Ha, Ho Dt Nghia, W Henry Boom, Catherine M Stein, Chiea C Khor, Guy E Thwaites, Hoang T Hai, Nguyen Tt Thuong, Xuling Chang, Sarah J Dunstan, Thomas R Hawn
Journal: Journal of Clinical Investigation (2025)

Immune and clinical outcomes to Mycobacterium tuberculosis (Mtb) infection vary greatly between individuals yet the underlying genetic and cellular mechanisms driving this heterogeneity remain poorly understood. We performed a cellular genome-wide association study (GWAS) to identify genetic variants associated with Mtb-induced monocyte transcriptional expression of IL1B, IL6, TNF, and IFNB1 via RNA-seq in a Ugandan cohort. Significantly associated variants were assessed for transferability in an independent Seattle cohort, further validated in vitro, and assessed for clinical phenotype associations. We identified 77 loci suggestively associated with Mtb-induced cytokine expression in monocytes in Uganda. SNPs associated with Mtb-induced TNF were enriched within alpha-linolenic acid metabolism pathway genes which was validated in vitro using PLA2 inhibitors. Four loci maintained significant associations in Seattle. We validated cytokine effect with siRNA knockdown for two of these loci which mapped to the genes SLIT3 and SLC1A1. Furthermore, exogenous treatment of macrophages with SLIT3 enhanced Mtb intracellular replication. Finally, SLC1A1 and SLIT3 variants were associated with susceptibility to tuberculous meningitis (TBM) and subsequent survival in a Vietnamese cohort, respectively. In sum, we identified multiple variants and pathways associated with Mtb-induced cytokine transcriptional responses that validated in vitro and were associated with clinical TB susceptibility.
Enteronephrohepatic Circulation of Bile Acids and Therapeutic Potential of Systemic Bile Acid Transporter Inhibitors
Authors: Ahmed Ghallab, Mattias Mandorfer, Guido Stirnimann, Joachim Geyer, Erik Lindström, Tom Luedde, Schalk van der Merwe, Jassin Rashidi-Alavijeh, Hartmut Schmidt, Saul J Karpen, Peter Fickert, Michael Trauner, Jan G Hengstler, Paul A Dawson
Journal: Journal of Hepatology (2025)

Together with carriers in liver and small intestine, kidney transporters function to conserve and compartmentalize bile acids in the enteronephrohepatic circulation. In patients with liver disease, systemic bile acid levels are elevated, undergo increased renal glomerular filtration, and contribute to the pathogenesis of cholemic nephropathy and acute kidney injury. In this review, we describe mechanisms for renal bile acid transport and highlight very recent discoveries that challenge current paradigms for the pathogenesis of cholemic nephropathy and renal tubule cast formation. We also discuss the therapeutic potential of inhibiting the kidney apical sodium-dependent bile acid transporter (ASBT) to redirect bile acids into urine for elimination, reduce hepatobiliary accumulation and systemic levels of bile acids, and treat cholemic nephropathy. In conclusion, a deeper understanding of the enteronephrohepatic bile acid axis is providing insights into novel strategies to protect both liver and kidney in patients with liver disease.
Tongue Swab-Based Molecular Diagnostics for Pulmonary Tuberculosis and Drug Resistance in Adults: A Prospective Multicenter Diagnostic Accuracy Study
Authors: Yilin Wang, Zichun Ma, Zubi Liu, Xiaowei Dong, Wei Shu, Mingchong Wei, Junwei Cui, Wei Shu, Rui Li, Wei Jing, Jin Shi, Bingnan Wang, Dan Shen, Chuan Qin, Rui Shao, Zanyan Wan, Juan Wu, Lanbo Luo, Lihua Huang, Yanjing Pan, Yuan Gao, Shanshan Li, Liang Li, Yu Pang
Journal: Journal of Infection (2025)

Tongue swabs have emerged as a promising non-invasive alternative for TB diagnosis. This study aimed to evaluate the diagnostic performance of tongue swab-based assays for detecting Mycobacterium tuberculosis (MTB) and anti-TB drug resistance. We conducted a multicenter study in five TB-designated hospitals in China from May to August 2024. Tongue swabs and sputum samples were collected from 720 adults with symptoms suggestive of pulmonary TB. PCR-based tongue swab testing targeting MTB-specific sequences was evaluated against microbiological reference standards (MRS) and Xpert MTB/RIF. Tongue swab-based targeted next generation sequencing was conducted to diagnose the drug-resistant TB. Tongue swab testing demonstrated high diagnostic accuracy, with a concordance rate of 95.1% (95% CI: 93.2-96.5) compared to Xpert MTB/RIF, and with a sensitivity of 88.6% (95% CI: 85.3-91.8) and specificity of 98.3% (95% CI: 97.0-99.7) compared to MRS. Tongue swabs supported detection of drug-resistant MTB using targeted next-generation sequencing, with detection rates of 98.66% for Ct <30, 91.53% for Ct 30-33, and 84.62% for Ct 33-34, declining sharply to 57.14% for Ct 34-35. PCR-based tongue swab testing offers a rapid, non-invasive alternative for TB diagnosis with high accuracy, particularly in paucibacillary cases or individuals unable to provide sputum. Although all participants in this study were able to provide sputum, tongue swabs may offer an alternative in situations where sputum collection is challenging. Further optimization of sampling and molecular techniques is essential to improve reliability and support broader implementation. Integrating tongue swab diagnostics with existing TB control programs could enhance the detection accuracy, improve drug resistance monitoring and reduce transmissions.
Burden of noninfectious ocular inflammatory disease in US ophthalmology practice
Authors: Matthew S. Hunt, K. Matthew McKay, Aaron Y. Lee, Cecilia S. Lee, Russell N. Van Gelder, Emily Y. Chew, Julia A. Haller, Leslie G. Hyman, Aaron Y. Lee, Cecilia S. Lee, Alice C. Lorch, Flora Lum, Joan W. Miller, Suzann Pershing
Journal: Ophthalmology (2025)
A non-inferiority randomised controlled trial of a Shorter Acetylcysteine Regimen for Paracetamol Overdose – the SARPO trial.
Authors: Geoffrey Isbister, Angela Chiew, Nicholas Buckley, Keith Harris, Ingrid Berling, Michael Downes, Colin Page, Katherine Isoardi
Journal: Journal of Hepatology (2025)

Paracetamol is a common overdose worldwide. Early acetylcysteine treatment can prevent hepatotoxicity. Multiple intravenous acetylcysteine regimens exist; the commonest recommending 300mg/kg over 20h. We investigated the effectiveness and safety of a shorter regimen in paracetamol overdoses ≤30g. In a multicentre non-inferiority randomised controlled trial, 204 patients from three hospitals with acute paracetamol overdose ≤ 30g presenting within 8h, were randomised to standard 20h acetylcysteine (200mg/kg/4h, 100mg/kg/16h) regimen or short 12h acetylcysteine (200mg/kg/4h, 50mg/kg/8h) regimen. The primary outcome was the absolute difference between alanine transaminase (ALT) 24h post-ingestion and admission ALT (ΔALT24). Secondary outcomes included ALT>150U/L at 24h and double admission ALT, systemic hypersensitivity and gastrointestinal adverse effects. The two groups were similar in age, gender, dose ingested, paracetamol concentration, baseline ALT, hospital, charcoal administration and time until acetylcysteine. The shorter regimen was non-inferior to the standard regimen. ΔALT24 for 107 patients given the shorter regimen was median -2U/L (Interquartile range [IQR]:-7 to 1U/L) compared to 97 given the standard regimen, median -1U/L (IQR:-5 to 1.5U/L); difference in medians of -1U/L; 95% confidence interval:-3 to 1U/L; less than the upper non-inferiority margin of 5). No patient receiving the shorter regimen had a 24h ALT double admission and >150U/L, compared to one receiving the standard regimen. No patient had an ALT>1000U/L. Systemic hypersensitivity reactions were similar between groups [9/107 (8%) for short versus 10/97 (10%) standard regimen]. Gastrointestinal adverse effects occurred in 78/107 patients (73%) receiving the short versus 63/97 (65%) receiving the standard regimen. The shorter 12h acetylcysteine regimen had the same effectiveness and safety as the standard 20h regimen in acute paracetamol overdoses ≤30g, almost halving the length of treatment required. Australian New Zealand Clinical Trials Registry number ACTRN12616001617459.