tbuckley/cabot-search huggingface dataset:
First Results of NURE-Combo: A Phase II Study of Neoadjuvant Nivolumab and Nab-Paclitaxel, Followed by Postsurgical Adjuvant Nivolumab, for Muscle-Invasive Bladder Cancer
Authors: Chiara Mercinelli, Marco Moschini, Antonio Cigliola, Benedetta Mattorre, Valentina Tateo, Giuseppe Basile, Laura L. Cogrossi, Brigida A. Maiorano, Damiano A. Patanè, Daniele Raggi, Giovanni L. Pastorino, Chiara Re, Maurizio Colecchia, Roberta Lucianò, Renzo Colombo, Giorgio Brembilla, Francesco De Cobelli, Alberto Briganti, Dean C. Pavlick, Jeffrey S. Ross, Francesco Montorsi, Matteo Bellone, Andrea Necchi
Journal: Journal of Clinical Oncology (2024)

PURPOSE To evaluate the activity and safety of nivolumab with nab-paclitaxel as neoadjuvant therapy, followed by radical cystectomy (RC) and postsurgical adjuvant nivolumab in patients with muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS Eligible patients had an Eastern Cooperative Oncology Group performance status of ≤1 and a T2-4aN0-1M0 stage with &gt;50% urothelial carcinoma histology and were ineligible for or refused cisplatin-based chemotherapy. Patients received four cycles of nivolumab 360 mg once every 3 weeks + nab-paclitaxel 125 mg/m 2 once on days 1 and 8, every 3 weeks, followed by RC, and then adjuvant nivolumab 360 mg once every 3 weeks × 13 cycles. The primary end point was the pathologic complete response (CR) rate (ypT0N0). Secondary end points were major pathologic response (ypT≤1N0), safety, event-free survival (EFS), and overall survival. RESULTS Thirty-one patients were enrolled from December 2021 to June 2023; 19 (61.3%) had a cT2 stage, two (6.5%) had N1 stage, and 16 (51.6%) had a variant histology. Five patients (16.1%) received less than four full courses of neoadjuvant treatment because of treatment-related adverse events (TRAEs). Grade 3/4 TRAEs occurred in eight patients (25.8%). Twenty-eight patients underwent RC, and three refused RC after evidence of clinical CR and received a redo transurethral resection of the bladder tumor (reTURBT). The trial met its primary end point: 10 patients (32.3%; 95% CI, 16.7 to 51.4) achieved an ypT0N0 response. By including those who underwent reTURBT, 22 (70.9%; 95% CI, 55 to 87) achieved an ypT≤1N0-x response. After a median follow-up of 12 months (range, 5-22), two patients had a disease relapse after surgery. The 12-month EFS was 89.8% (95% CI, 79.5 to 100). CONCLUSION To our knowledge, the first results from NURE-Combo trial suggest that this combination could expand the therapeutic opportunities of immune-chemotherapy in patients with MIBC.
Effect of Adding Electroacupuncture to Standard Triple Antiemetic Therapy on Chemotherapy-Induced Nausea and Vomiting: A Randomized Controlled Clinical Trial
Authors: Guoshuang Shen, Dengfeng Ren, Fuxing Zhao, Miaozhou Wang, Zhen Liu, Xiumei Feng, Yingjian He, Xinlan Liu, Xiaoling Ling, Yi Zhao, Feixue Song, Jiyan Ma, Enxi Li, Tong She, Zhilin Liu, Zitao Li, Shifen Huang, Yongzhi Chen, Jingru Yang, Xuan Li, Li Duan, Mengting Da, Yonghui Zheng, Yongxin Li, Jiuda Zhao
Journal: Journal of Clinical Oncology (2024)

PURPOSE We aim to determine the effectiveness of adding electroacupuncture to standard triple antiemetic therapy for treating chemotherapy-induced nausea and vomiting (CINV). METHODS From March 2022 to December 2023, a randomized, blind, sham-controlled trial conducted across six Chinese hospitals investigated patients with breast cancer undergoing highly emetogenic chemotherapy (HEC). Patients were randomly assigned to either true electroacupuncture (n = 120) or sham electroacupuncture (n = 119) groups, with both groups receiving standard triple antiemetic therapy. The primary end point was the proportion of complete protection (no vomiting, no need for rescue treatment, and no significant nausea, as evaluated using the visual analog scale [VAS]) within 120 hours after receiving HEC. RESULTS Among 239 randomly assigned patients, 235 (98.3%) completed the trial. In the full analysis set, compared with the sham electroacupuncture group, the true electroacupuncture group demonstrated a significant increase in the complete protection rate from 34.5% to 52.9% ( P = .004). Additionally, true electroacupuncture also showed enhanced total control (4.3% v 13.4%; P = .014), no significant nausea (37.9% v 58.8%; P = .001), no nausea (4.3% v 13.4%; P = .014), and nausea VAS score = 0 mm (4.3% v 12.6%; P = .023). However, the occurrence of no vomiting in the overall stage was similar (76.7% v 73.9%; P = .622) in both groups. Post hoc exploratory analysis showed a significantly higher rate of complete protection during the delayed stage in the true electroacupuncture group compared with the sham electroacupuncture group, with no significant difference observed during the acute stage. CONCLUSION Adding true electroacupuncture to standard triple antiemetic therapy significantly enhances the efficacy of CINV treatment in patients with breast cancer receiving HEC.
Reconstruction of patient-specific confounders in AI-based radiologic image interpretation using generative pretraining
Authors: Tianyu Han, Laura Žigutytė, Luisa Huck, Marc Sebastian Huppertz, Robert Siepmann, Yossi Gandelsman, Christian Blüthgen, Firas Khader, Christiane Kuhl, Sven Nebelung, Jakob Nikolas Kather, Daniel Truhn
Journal: Cell Reports Medicine (2024)

Reliably detecting potentially misleading patterns in automated diagnostic assistance systems, such as those powered by artificial intelligence (AI), is crucial for instilling user trust and ensuring reliability. Current techniques fall short in visualizing such confounding factors. We propose DiffChest, a self-conditioned diffusion model trained on 515,704 chest radiographs from 194,956 patients across the US and Europe. DiffChest provides patient-specific explanations and visualizes confounding factors that might mislead the model. The high inter-reader agreement, with Fleiss' kappa values of 0.8 or higher, validates its capability to identify treatment-related confounders. Confounders are accurately detected with 10%-100% prevalence rates. The pretraining process optimizes the model for relevant imaging information, resulting in excellent diagnostic accuracy for 11 chest conditions, including pleural effusion and heart insufficiency. Our findings highlight the potential of diffusion models in medical image classification, providing insights into confounding factors and enhancing model robustness and reliability.
Baseline Immune State and T-cell Clonal Kinetics are Associated with Durable Response to CAR-T Therapy in Large B-cell Lymphoma
Authors: Katie Maurer, Isabella N Grabski, Roch Houot, Satyen H. Gohil, Shogo Miura, Robert A Redd, Haoxiang Lyu, Wesley Lu, Yohei Arihara, Justin Budka, Mikaela McDonough, Michela Ansuinelli, Carol G Reynolds, Heather Jacene, Shuqiang Li, Kenneth J Livak, Jerome Ritz, Brodie Miles, Mike Mattie, Donna S. Neuberg, Rafael A. Irizarry, Philippe Armand, Catherine J Wu, Caron A. Jacobson
Journal: Blood (2024)
Detecting altered hepatic lipid oxidation by MRI in an animal model of MASLD
Authors: Marc McLeod, Mario C Chang, Anna Rushin, Mukundan Ragavan, Rohit Mahar, Gaurav Sharma, Arshee Badar, Anthony Giacalone, Max E Glanz, Vinay R Malut, Dalton Graham, Nishanth E Sunny, James A Bankson, Kenneth Cusi, Matthew E Merritt
Journal: Cell Reports Medicine (2024)

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing annually and affects over a third of US adults. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by severe hepatocyte injury, inflammation, and eventual advanced fibrosis or cirrhosis. MASH is predicted to become the primary cause of liver transplant by 2030. Although the etiology of MASLD/MASH is incompletely understood, dysregulated fatty acid oxidation is implicated in disease pathogenesis. Here, we develop a method for estimating hepatic β-oxidation from the metabolism of [D
Durvalumab With or Without Tremelimumab in Combination With Chemotherapy in First-Line Metastatic NSCLC: Five-Year Overall Survival Outcomes From the Phase 3 POSEIDON Trial
Authors: Solange Peters, Byoung Chul Cho, Alexander V Luft, Jorge Alatorre-Alexander, Sarayut Lucien Geater, Konstantin Laktionov, Dmytro Trukhin, Sang-We Kim, Grygorii M Ursol, Maen Hussein, Farah Louise Lim, Cheng-Ta Yang, Luiz Henrique Araujo, Haruhiro Saito, Niels Reinmuth, Caitlin Lowery, Helen Mann, Ross Stewart, Haiyi Jiang, Edward B Garon, Tony Mok, Melissa L Johnson
Journal: Journal of Thoracic Oncology (2024)

The primary analysis (median follow-up 34.9 mo across all arms) of the phase 3 POSEIDON study revealed a statistically significant overall survival (OS) improvement with first-line tremelimumab plus durvalumab and chemotherapy (T+D+CT) versus CT in patients with EGFR and ALK wild-type metastatic NSCLC (mNSCLC). D+CT had a trend for OS improvement versus CT that did not reach statistical significance. This article reports prespecified OS analyses after long-term follow-up (median >5 y). A total of 1013 patients were randomized (1:1:1) to T+D+CT, D+CT, or CT, stratified by tumor cell programmed cell death ligand-1 (PD-L1) expression (≥50% versus <50%), disease stage (IVA versus IVB), and tumor histologic type (squamous versus nonsquamous). Serious adverse events were collected during follow-up. After a median follow-up of 63.4 months across all arms, T+D+CT had sustained OS benefit versus CT (hazard ratio [HR] = 0.76, 95% confidence interval [CI]: 0.64-0.89; 5-y OS: 15.7% versus 6.8%). OS improvement with D+CT versus CT (HR = 0.84, 95% CI: 0.72-1.00; 5-y OS: 13.0%) was consistent with the primary analysis. OS benefit with T+D+CT versus CT remained more pronounced in nonsquamous (HR = 0.69, 95% CI: 0.56-0.85) versus squamous (HR = 0.85, 95% CI: 0.65-1.10) mNSCLC. OS benefit with T+D+CT versus CT was still evident regardless of PD-L1 expression, including patients with PD-L1 tumor cell less than 1%, and remained evident in STK11-mutant (nonsquamous), KEAP1-mutant, and KRAS-mutant (nonsquamous) mNSCLC. No new safety signals were identified. After a median follow-up of more than 5 years, T+D+CT had durable long-term OS benefit versus CT, supporting its use as first-line treatment in mNSCLC, including in patient subgroups with harder-to-treat disease.
Association between surgical admissions, cognition, and neurodegeneration in older people: a population-based study from the UK Biobank
Authors: Jennifer Taylor, Kristy P Robledo, Vicente Medel, Gillian Heller, Thomas Payne, Jordan Wehrman, Cameron Casey, Phillip F Yang, Bryan M Krause, Richard Lennertz, Sharon Naismith, Armando Teixeira-Pinto, Robert D Sanders
Journal: The Lancet Healthy Longevity (2024)

Previous studies have shown that major surgical and medical hospital admissions are associated with cognitive decline in older people (aged 40-69 years at recruitment), which is concerning for patients and caregivers. We aimed to validate these findings in a large cohort and investigate associations with neurodegeneration using MRI.
Acutely blocking excessive mitochondrial fission prevents chronic neurodegeneration after traumatic brain injury
Authors: Preethy S Sridharan, Yeojung Koh, Emiko Miller, Di Hu, Suwarna Chakraborty, Sunil Jamuna Tripathi, Teresa R Kee, Kalyani Chaubey, Edwin Vázquez-Rosa, Sarah Barker, Hui Liu, Rose A León-Alvarado, Kathryn Franke, Coral J Cintrón-Pérez, Matasha Dhar, Min-Kyoo Shin, Margaret E Flanagan, Rudolph J Castellani, Tamar Gefen, Marina Bykova, Lijun Dou, Feixiong Cheng, Brigid M Wilson, Hisashi Fujioka, David E Kang, Jung-A A Woo, Bindu D Paul, Xin Qi, Andrew A Pieper
Journal: Cell Reports Medicine (2024)

Progression of acute traumatic brain injury (TBI) into chronic neurodegeneration is a major health problem with no protective treatments. Here, we report that acutely elevated mitochondrial fission after TBI in mice triggers chronic neurodegeneration persisting 17 months later, equivalent to many human decades. We show that increased mitochondrial fission after mouse TBI is related to increased brain levels of mitochondrial fission 1 protein (Fis1) and that brain Fis1 is also elevated in human TBI. Pharmacologically preventing Fis1 from binding its mitochondrial partner, dynamin-related protein 1 (Drp1), for 2 weeks after TBI normalizes the balance of mitochondrial fission/fusion and prevents chronically impaired mitochondrial bioenergetics, oxidative damage, microglial activation and lipid droplet formation, blood-brain barrier deterioration, neurodegeneration, and cognitive impairment. Delaying treatment until 8 months after TBI offers no protection. Thus, time-sensitive inhibition of acutely elevated mitochondrial fission may represent a strategy to protect human TBI patients from chronic neurodegeneration.
Frailty and functional dependency in a multicenter cohort of older adults with psoriasis: prevalence and extent of and implications for psoriasis management
Authors: Elke L M Ter Haar, Juul M P A van den Reek, Mahshid Sadat Chenarani Moghadam, Yvonne Schoon, Marloes M Kleinpenning, Elke M G J de Jong, Satish F K Lubeek
Journal: Journal of the American Academy of Dermatology (2024)
Response to Caplan et al., “Clinico-mycological and therapeutic updates on cutaneous dermatophytic infections in the era of Trichophyton indotineae; Focus on Griseofulvin”
Authors: Ananta Khurana, Savitha Sharath, Kabir Sardana, Anuradha Chowdhary
Journal: Journal of the American Academy of Dermatology (2024)
Optimising HIV spending in 12 eastern European and central Asian countries: a modelling study
Authors: Debra C Ten Brink, Anna L Bowring, Rowan Martin-Hughes, Nisaa Wulan, Yinzong Xiao, Kelvin Burke, Tom Tidhar, Tom Walsh, Sherrie L Kelly, Andrew Shattock, Tom Palmer, Corina Maxim, Shufang Zhang, Nick Scott
Journal: The Lancet HIV (2024)
Mechanisms and causes of death after abdominal surgery in low-income and middle-income countries: a secondary analysis of the FALCON trial
Authors: Sivesh Kamarajah, Lawani Ismail, Adesoji Ademuyiwa, Adewale O Adisa, Bruce Biccard, Dhruva Ghosh, Fareeda Galley, Parvez D Haque, Ewen Harrison, JC Allen Ingabire, Bryar Kadir, Souliath Lawani, Virginia Ledda, Rachel Lillywhite, Janet Martin, Antonio Ramos de la Medina, Dion Morton, Dmitri Nepogodiev, Faustin Ntirenganya, Omar Omar, Maria Picciochi, Stephen Tabiri, James Glasbey, Aneel Bhangu, Adesoji Ademuyiwa, Adewale O Adisa, Aneel Bhangu, Felicity Brant, Peter Brocklehurst, Sohini Chakrabortee, Dhruva Ghosh, James Glasbey, Frank Enoch Gyamfi, Parvez D Haque, Pollyanna Hardy, Ewen Harrison, Emily Heritage, JC Allen Ingabire, Lawani Ismail, Karolin Kroese, Carmela Lapitan, Rachel Lillywhite, David Lissauer, Laura Magill, Antonio Ramos de la Medina, Punam Mistry, Mark Monahan, Rachel Moore, Dion Morton, Dmitri Nepogodiev, Faustin Ntirenganya, Omar Omar, Thomas Pinkney, Tracy Roberts, Joana Simoes, Donna Smith, Stephen Tabiri, Neil Winkles
Journal: The Lancet Global Health (2024)
MAIT cell heterogeneity across paired human tissues reveals specialization of distinct regulatory and enhanced effector profiles
Authors: Tobias Kammann, Curtis Cai, Takuya Sekine, Elli Mouchtaridi, Caroline Boulouis, Vera Nilsén, Olga Rivera Ballesteros, Thomas R. Müller, Yu Gao, Elisa J. M. Raineri, Akhirunnesa Mily, Sarah Adamo, Christian Constantz, Julia Niessl, Whitney Weigel, Efthymia Kokkinou, Christopher Stamper, Anne Marchalot, John Bassett, Sabrina Ferreira, Inga Rødahl, Nicole Wild, Demi Brownlie, Chris Tibbitt, Jeffrey Y. W. Mak, David P. Fairlie, Edwin Leeansyah, Jakob Michaelsson, Nicole Marquardt, Jenny Mjösberg, Carl Jorns, Marcus Buggert, Johan K. Sandberg
Journal: Science Immunology (2024)

Mucosal-associated invariant T (MAIT) cells are unconventional T cells that recognize microbial riboflavin pathway metabolites presented by evolutionarily conserved MR1 molecules. We explored the human MAIT cell compartment across organ donor–matched blood, barrier, and lymphoid tissues. MAIT cell population size was donor dependent with distinct tissue compartmentalization patterns and adaptations: Intestinal CD103 + resident MAIT cells presented an immunoregulatory CD39 high CD27 low profile, whereas MAIT cells expressing NCAM1/CD56 dominated in the liver and exhibited enhanced effector capacity with elevated response magnitude and polyfunctionality. Both intestinal CD39 high and hepatic CD56 + adaptations accumulated with donor age. CD56 + MAIT cells displayed limited T cell receptor–repertoire breadth, elevated MR1 binding, and a transcriptional profile skewed toward innate activation pathways. Furthermore, CD56 was dynamically up-regulated to a persistent steady-state equilibrium after exposure to antigen or IL-7. In summary, we demonstrate functional heterogeneity and tissue site adaptation in resident MAIT cells across human barrier tissues with distinct regulatory and effector signatures.
Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity
Authors: Anna Appios, James Davies, Sofia Sirvent, Stephen Henderson, Sébastien Trzebanski, Johannes Schroth, Morven L. Law, Inês Boal Carvalho, Marlene Magalhaes Pinto, Cyril Carvalho, Howard Yuan-Hao Kan, Shreya Lovlekar, Christina Major, Andres Vallejo, Nigel J. Hall, Michael Ardern-Jones, Zhaoyuan Liu, Florent Ginhoux, Sian M. Henson, Rebecca Gentek, Elaine Emmerson, Steffen Jung, Marta E. Polak, Clare L. Bennett
Journal: Science Immunology (2024)

Langerhans cells (LCs) are distinct among phagocytes, functioning both as embryo-derived, tissue-resident macrophages in skin innervation and repair and as migrating professional antigen-presenting cells, a function classically assigned to dendritic cells (DCs). Here, we demonstrate that both intrinsic and extrinsic factors imprint this dual identity. Using ablation of embryo-derived LCs in the murine adult skin and tracking differentiation of incoming monocyte-derived replacements, we found intrinsic intraepidermal heterogeneity. We observed that ontogenically distinct monocytes give rise to LCs. Within the epidermis, Jagged-dependent activation of Notch signaling, likely within the hair follicle niche, provided an initial site of LC commitment before metabolic adaptation and survival of monocyte-derived LCs. In the human skin, embryo-derived LCs in newborns retained transcriptional evidence of their macrophage origin, but this was superseded by DC-like immune modules after postnatal expansion. Thus, adaptation to adult skin niches replicates conditioning of LC at birth, permitting repair of the embryo-derived LC network.
IgE plasma cells are transcriptionally and functionally distinct from other isotypes
Authors: Andrea Vecchione, Joseph C. Devlin, Carley Tasker, Venkat Raman Ramnarayan, Paul Haase, Eva Conde, Devin Srivastava, Gurinder S. Atwal, Pierre Bruhns, Andrew J. Murphy, Matthew A. Sleeman, Andre Limnander, Wei Keat Lim, Seblewongel Asrat, Jamie M. Orengo
Journal: Science Immunology (2024)

Understanding the phenotypic and transcriptional signature of immunoglobulin E (IgE)–producing cells is fundamental to plasma cell (PC) biology and development of therapeutic interventions for allergy. Here, using a mouse model of intranasal house dust mite (HDM) exposure, we showed that short-lived IgE PCs emerge in lung draining lymph nodes (dLNs) during early exposure (&lt;3 weeks) and long-lived IgE PCs accumulate in the bone marrow (BM) with prolonged exposure (&gt;7 weeks). IgE PCs had distinct surface and gene expression profiles in these different tissues compared with other Ig isotypes. IgE BMPCs up-regulated genes associated with prosurvival and BM homing, whereas IgE dLN PCs expressed genes associated with recent class switching and differentiation. IgE PCs also exhibited higher expression of endoplasmic reticulum (ER) stress and protein coding genes and higher antibody secretion rate when compared with IgG1. Overall, this study highlights the unique developmental path and transcriptional signature of short-lived and long-lived IgE PCs.
Palliative radiotherapy versus best supportive care in patients with painful hepatic cancer (CCTG HE1): a multicentre, open-label, randomised, controlled, phase 3 study
Authors: Laura A Dawson, Jolie Ringash, Alysa Fairchild, Paul Stos, Kristopher Dennis, Aamer Mahmud, Teri Lynn Stuckless, Francois Vincent, David Roberge, Matthew Follwell, Raimond K W Wong, Derek J Jonker, Jennifer J Knox, Camilla Zimmermann, Philip Wong, Aisling S Barry, Marc Gaudet, Rebecca K S Wong, Thomas G Purdie, Dongsheng Tu, Christopher J O'Callaghan
Journal: The Lancet Oncology (2024)
Development of a Core Outcome Set for Studies Assessing Interventions for Diabetes-Related Foot Ulceration
Authors: Aleksandra Staniszewska, Frances Game, Jane Nixon, David Russell, David G. Armstrong, Christopher Ashmore, Sicco A. Bus, Jayer Chung, Vivienne Chuter, Ketan Dhatariya, George Dovell, Michael Edmonds, Robert Fitridge, Catherine Gooday, Emma J. Hamilton, Amy Jones, Venu Kavarthapu, Lawrence A. Lavery, Joseph L. Mills, Matilde Monteiro-Soares, Maia Osborne-Grinter, Edgar J.G. Peters, Joseph Shalhoub, Jaap van Netten, Dane K. Wukich, Robert J. Hinchliffe
Journal: Diabetes Care (2024)

OBJECTIVE Diabetes affects 537 million people globally, with 34% expected to develop foot ulceration in their lifetime. Diabetes-related foot ulceration causes strain on health care systems worldwide, necessitating provision of high-quality evidence to guide their management. Given heterogeneity of reported outcomes, a core outcome set (COS) was developed to standardize outcome measures in studies assessing treatments for diabetes-related foot ulceration. RESEARCH DESIGN AND METHODS The COS was developed using Core Outcome Measures in Effectiveness Trials (COMET) methodology. A systematic review and patient interviews generated a long list of outcomes that were rated by patients and experts using a nine-point Likert scale (from 1 [not important] to 9 [critical]) in the first round of the Delphi survey. Based on predefined criteria, outcomes without consensus were reprioritized in a second Delphi round. Critical outcomes and those without consensus after two Delphi rounds were discussed in the consensus meeting where the COS was ratified. RESULTS The systematic review and patient interviews generated 103 candidate outcomes. The two consecutive Delphi rounds were completed by 336 and 176 respondents, resulting in an overall second round response rate of 52%. Of 37 outcomes discussed in the consensus meeting (22 critical and 15 without consensus after the second round), 8 formed the COS: wound healing, time to healing, new/recurrent ulceration, infection, major amputation, minor amputation, health-related quality of life, and mortality. CONCLUSIONS The proposed COS for studies assessing treatments for diabetes-related foot ulceration was developed using COMET methodology. Its adoption by the research community will facilitate assessment of comparative effectiveness of current and evolving interventions.