tbuckley/cabot-search huggingface dataset:
Phase 1 dose-escalation trial using convection-enhanced delivery (CED) of radio-immunotheranostic 124I-Omburtamab for diffuse intrinsic pontine glioma (DIPG)
Authors: Mark M Souweidane, Evan D Bander, Pat Zanzonico, Anne S Reiner, Nicole Manino, Sofia Haque, Jorge A Carrasquillo, Serge K Lyashchenko, Sunitha B Thakur, Jason S Lewis, Maria Donzelli, Nai-Kong V Cheung, Steven M Larson, Kim Kramer, Neeta Pandit-Taskar, Ira J Dunkel
Journal: Neuro-Oncology (2025)

Abstract Background Median survival for patients with Diffuse Intrinsic Pontine Glioma (DIPG) is 8-12 months. Methods A phase 1, open label, 3 + 3 dose escalation trial delivered radiolabeled 124I-Omburtamab, targeting B7-H3, using MR-guided stereotactic convection enhanced delivery (CED) into the brainstem of pediatric DIPG patients. CED was performed after completion of standard-of-care external-beam radiation therapy (EBRT). Fifty children were treated and evaluable. 124I-Omburtamab activity was escalated from 0.25-10.0 mCi (9.25-370 MBq) and volume escalated from 0.25 ml-10.0 ml with serial PET/MRI post-administration. Safety was the primary outcome. National Cancer Institute Common Terminology Criteria for Adverse Events were assessed for 30 days following CED of 124I-Omburtamab. Secondary outcomes included overall survival and lesion-to-whole-body absorbed dose ratio. Results The maximum tolerated activity per study protocol was determined to be 6mCi (222 MBq). The overall mean (±SD) total absorbed dose in the lesion per unit injected activity was 35.2 ± 18 cGy/MBq with a high lesion-to-whole-body absorbed dose ratio averaging 816, across all activity levels. Eleven patients had treatment-related grade 3 CNS toxicities with no grade-4 or -5 CNS toxicities. Five dose-limiting toxicity events occurred. Median survival was 15.29 months from diagnosis (95% CI: 12.20 – 16.83 months). Survival rate estimates at 1, 2, and 3 years were 65.4% (CI 53.3-80.1%), 18.4% (CI: 10.2-33.2%), and 11.7% (CI: 5.3-25.7%), respectively. Conclusions Administration of 124I-Omburtamab via CED is a safe treatment option for DIPG, with a maximum tolerated activity level identified. This study represents the first in-human theranostic use of a 124I radiopharmaceutical, simultaneously, as an imaging and therapeutic agent.
End-of-Life Care in Glioblastoma: A Population-Based Study
Authors: Yosef Ellenbogen, Shervin Taslimi, Jonas Shellenberger, Susan B Brogly, Gelareh Zadeh, Ryan Alkins
Journal: Neuro-Oncology (2025)

The end-of-life (EoL) phase of care is inevitable for glioblastoma (GBM) patients; however, it lacks standardization. This study aimed to characterize the utilization of care at EoL in GBM patients, focusing on trends over time, regional variability, and the influence of socioeconomic factors. This was a retrospective population-based cohort study of all patients with GBM treated in Ontario between 1994 - 2018 using administrative health data and registries available at ICES (formerly the Institute for Clinical Evaluative Sciences). The proportion of patients with palliative care, supportive care, and in-hospital deaths by year of diagnosis was estimated, and trends assessed with the Cochrane-Armitage trend test. The cohort included 9,013 GBM patients. There was an increase in supportive care components over the study time-period (29.6% in 1994 - 1998 to 60.2% in 2014 - 2018; p < 0.0001). There was a simultaneous decrease in in-hospital deaths (50.5% in 1994 - 1998 to 21.4% in 2014 - 2018; p<0.001) and hospitalizations within 30 days before death (65.5% in 1994-1998 to 51.7% in 2014 - 2018, p<0.001). This coincided with an increased in chemotherapy administration within 14 days of death and ICU admissions within 30 days of death over the studied period of time. Patient neighborhood income level and geographic location influenced EoL care patterns with regards to both supportive and aggressive components. Over time there was an expansion of both inpatient and outpatient palliative care use at EoL. Rurality and neighborhood income quintile significantly influenced the utilization of these resources, underscoring the need for standardized EoL care practices.
Planning for end of life in the past and present: historical, legal and clinical perspectives on ReSPECT
Authors: James David van Oppen, Sarah Gunn, Timothy John Coats, Nataly Papadopoulou, Michaela Senkova, Sarah Tarlow, Elizabeth Wicks
Journal: Journal of the Royal Society of Medicine (2025)

The ReSPECT (‘Recommended Summary Plan for Emergency Care and Treatment’) process was developed in the UK to guide and document conversations and decision-making with patients and their relatives around intervention during critical deterioration. This includes advising whether resuscitation should be attempted when a person dies. Current medical preparation for death is qualitatively different to social behaviours by people in the past and presents some controversies when considering the legal status of death-related decisions. In this article, we discuss our interdisciplinary perspectives as archaeological, historical, legal, medical and clinical psychologist academics following a historico-medico-legal appraisal of the ReSPECT process as situated in the current UK legal and cultural landscape. We review controversies and conundrums, and contextualise and contrast the current position to preparing for death and dying in the past.
Corrigendum to “An NIR-responsive hydrogel loaded with polydeoxyribonucleotide nano-vectors for enhanced chronic wound healing” [Biomaterials 314 (2025) 122789]
Authors: Yanzhen Sun, Yao Li, Xiaokang Ding, Pan Xu, Xiaodong Jing, Hailin Cong, Hao Hu, Bing Yu, Fu-Jian Xu
Journal: Biomaterials (2025)
The integrated stress response in neurodegenerative diseases
Authors: Maria Astrid Bravo-Jimenez, Shivangi Sharma, Soheila Karimi-Abdolrezaee
Journal: Molecular Neurodegeneration (2025)

Abstract The integrated stress response (ISR) is a conserved network in eukaryotic cells that mediates adaptive responses to diverse stressors. The ISR pathway ensures cell survival and homeostasis by regulating protein synthesis in response to internal or external stresses. In recent years, the ISR has emerged as an important regulator of the central nervous system (CNS) development, homeostasis and pathology. Dysregulation of ISR signaling has been linked to several neurodegenerative diseases. Intriguingly, while acute ISR provide neuroprotection through the activation of cell survival mechanisms, prolonged ISR can promote neurodegeneration through protein misfolding, oxidative stress, and mitochondrial dysfunction. Understanding the molecular mechanisms and dynamics of the ISR in neurodegenerative diseases aids in the development of effective therapies. Here, we will provide a timely review on the cellular and molecular mechanisms of the ISR in neurodegenerative diseases. We will highlight the current knowledge on the dual role that ISR plays as a protective or disease worsening pathway and will discuss recent advances on the therapeutic approaches that have been developed to target ISR activity in neurodegenerative diseases.
Correspondence: Epithelial Barrier Dysfunction: Do Not Forget Functional Dyspepsia!
Authors: Jan Tack, Tim Vanuytsel, Florencia Carbone, Karen Van den Houte, Bert Broeders, Lukas Balsiger, Matthias Ceulemans, Cedric Van de Bruaene, Pauline Huyghe, Jara Lehoucq
Journal: Allergy (2025)
Plasma proteome variation and its genetic determinants in children and adolescents
Authors: Lili Niu, Sara Elizabeth Stinson, Louise Aas Holm, Morten Asp Vonsild Lund, Cilius Esmann Fonvig, Leonardo Cobuccio, Jonas Meisner, Helene Bæk Juel, Joao Fadista, Maja Thiele, Aleksander Krag, Jens-Christian Holm, Simon Rasmussen, Torben Hansen, Matthias Mann
Journal: Nature Genetics (2025)

Abstract Our current understanding of the determinants of plasma proteome variation during pediatric development remains incomplete. Here, we show that genetic variants, age, sex and body mass index significantly influence this variation. Using a streamlined and highly quantitative mass spectrometry-based proteomics workflow, we analyzed plasma from 2,147 children and adolescents, identifying 1,216 proteins after quality control. Notably, the levels of 70% of these were associated with at least one of the aforementioned factors, with protein levels also being predictive. Quantitative trait loci (QTLs) regulated at least one-third of the proteins; between a few percent and up to 30-fold. Together with excellent replication in an additional 1,000 children and 558 adults, this reveals substantial genetic effects on plasma protein levels, persisting from childhood into adulthood. Through Mendelian randomization and colocalization analyses, we identified 41 causal genes for 33 cardiometabolic traits, emphasizing the value of protein QTLs in drug target identification and disease understanding.
Atezolizumab following definitive chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma – a multicenter phase 2 trial (EPOC1802)
Authors: Hideaki Bando, Shogo Kumagai, Daisuke Kotani, Saori Mishima, Takuma Irie, Kota Itahashi, Yosuke Tanaka, Takumi Habu, Sayuri Fukaya, Masaki Kondo, Takahiro Tsushima, Hiroki Hara, Shigenori Kadowaki, Ken Kato, Keisho Chin, Kensei Yamaguchi, Shun-ichiro Kageyama, Hidehiro Hojo, Masaki Nakamura, Hidenobu Tachibana, Masashi Wakabayashi, Makoto Fukui, Nozomu Fuse, Shohei Koyama, Hiroyuki Mano, Hiroyoshi Nishikawa, Kohei Shitara, Takayuki Yoshino, Takashi Kojima
Journal: Nature Cancer (2025)

Platinum-based definitive chemoradiotherapy (dCRT) is the standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) that invades the aorta, vertebral body or trachea; however, complete response rates remain low (11–25%), leading to poor survival. To evaluate the additive efficacy of the anti-PD-L1 antibody drug atezolizumab, we conducted a phase 2, multicenter, single-arm trial of 1 year of atezolizumab treatment following dCRT in 40 patients with unresectable locally advanced ESCC recruited from seven Japanese centers (UMIN000034373). The confirmed complete response (cCR) rate (primary end point) of the first consecutive 38 patients was 42.1% (90% CI 28.5–56.7%). Regarding the secondary end points, the median progression-free survival and 12-month progression-free survival rates of all 40 patients were 3.2 months and 29.6%, respectively, and the preliminary median overall survival with short-term follow-up and 12-month overall survival rate were 31.0 months and 65.8%, respectively. Other secondary end points evaluated included the cCR rate determined by an investigator's assessment in the locoregionally recurrent ESCC cohort, cCR rate determined by central assessment, overall response rate and incidence of adverse events. No treatment-related death occurred during the study. Atezolizumab monotherapy after dCRT resulted in a promising cCR rate, although long-term survival data are required. Bando et al. perform a phase II trial of atezolizumab monotherapy following platinum-based definitive chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma and report a complete response rate of 42%.
Reduced-energy diet in women with gestational diabetes: the dietary intervention in gestational diabetes DiGest randomized clinical trial
Authors: Laura C Kusinski, Danielle Jones, Nooria Atta, Elizabeth Turner, Suzanne Smith, Linda M Oude Griep, Kirsten Rennie, Emanuella De Lucia Rolfe, Stephen J Sharp, Vern Farewell, Helen R Murphy, Roy Taylor, Claire L Meek
Journal: Nature Medicine (2025)
Pro-inflammatory macrophages produce mitochondria-derived superoxide by reverse electron transport at complex I that regulates IL-1β release during NLRP3 inflammasome activation
Authors: Alva M. Casey, Dylan G. Ryan, Hiran A. Prag, Suvagata Roy Chowdhury, Eloïse Marques, Keira Turner, Anja V. Gruszczyk, Ming Yang, Dane M. Wolf, Jan Lj. Miljkovic, Joyce Valadares, Patrick F. Chinnery, Richard C. Hartley, Christian Frezza, Julien Prudent, Michael P. Murphy
Journal: Nature Metabolism (2025)

Abstract Macrophages stimulated by lipopolysaccharide (LPS) generate mitochondria-derived reactive oxygen species (mtROS) that act as antimicrobial agents and redox signals; however, the mechanism of LPS-induced mitochondrial superoxide generation is unknown. Here we show that LPS-stimulated bone-marrow-derived macrophages produce superoxide by reverse electron transport (RET) at complex I of the electron transport chain. Using chemical biology and genetic approaches, we demonstrate that superoxide production is driven by LPS-induced metabolic reprogramming, which increases the proton motive force (∆p), primarily as elevated mitochondrial membrane potential (Δψ m ) and maintains a reduced CoQ pool. The key metabolic changes are repurposing of ATP production from oxidative phosphorylation to glycolysis, which reduces reliance on F 1 F O -ATP synthase activity resulting in a higher ∆p, while oxidation of succinate sustains a reduced CoQ pool. Furthermore, the production of mtROS by RET regulates IL-1β release during NLRP3 inflammasome activation. Thus, we demonstrate that ROS generated by RET is an important mitochondria-derived signal that regulates macrophage cytokine production.
Principles for the Future of Biomedical Research in the United States and Optimizing the National Institutes of Health: A Presidential Advisory From the American Heart Association
Authors: Joseph C. Wu, Donna K. Arnett, Ivor J. Benjamin, Mark A. Creager, Robert A. Harrington, Joseph A. Hill, P. Michael Ho, Steven R. Houser, Stephanie Scarmo, Svati H. Shah, Gordon F. Tomaselli
Journal: Circulation (2025)

Groundbreaking achievements in science and medicine have contributed to reductions in cardiovascular disease and stroke mortality over the past 7 decades. Many of these advances were supported through investments by the National Institutes of Health, the global leader in funding biomedical research. This public investment has produced important economic returns, including supporting &gt;400 000 jobs and roughly $93 billion in economic activity in the United States. Unfortunately, public funding has not kept pace with the burden of disease or rates of inflation. As the nation’s oldest and largest volunteer organization dedicated to fighting heart disease and stroke, research is critical to the American Heart Association’s mission. Given the American Heart Association’s unique position in representation of patients, clinicians, and scientists and as a research funder, we offer the following principles to optimize the future of the US biomedical research enterprise in general and the National Institutes of Health in particular. Specifically, the United States should continue to prioritize innovative and impactful research; to improve efficiency and transparency in its peer review process; to lead in translating evidence into practice; to support the current and future biomedical workforce; and to ensure robust and reliable public investment for the future. The American Heart Association reiterates our strong support for the National Institutes of Health and federal agencies that fund and implement biomedical and population-based research initiatives, which yield important economic returns. These agencies are vital to support today’s current and future health challenges, to drive foundational science, to improve patient health, to reduce the global disease burden, to address upstream and preventive strategies, and to improve the value of our public health and health care investments.
Enhanced paracrine action of FGF21 in stromal cells delays thymic aging
Authors: Yun-Hee Youm, Christy Gliniak, Yuan Zhang, Tamara Dlugos, Philipp E. Scherer, Vishwa Deep Dixit
Journal: Nature Aging (2025)

Age-related thymic involution precedes aging of all other organs in vertebrates and initiates the process of declining T cell diversity, which leads to eventual immune dysfunction. Whether FGF21, a liver-derived pro-longevity hormone that is also produced in thymic stroma, including by adipocytes, controls the mechanism of thymic demise is incompletely understood. Here, we demonstrate that elevation of FGF21 in thymic epithelial cells (TECs) and in adipocytes protects against thymic aging, whereas conditional hepatic overexpression did not impact thymic biology in aged mice. Notably, elevation of thymic FGF21 increased naïve CD8 T cells in aged animals and extended healthspan. Mechanistically, thymic FGF21 overexpression elevated TECs and reduced fibroadipogenic cells. Ablation of β-klotho, the obligatory co-receptor for FGF21 in Foxn1+ TECs, accelerated thymic aging, suggesting regulation of TECs by FGF21 is partially required for thymic lymphopoiesis. These findings establish that paracrine FGF21 improves thymic function and delays immune aging. Youm et al. demonstrate that elevating locally derived FGF21 delays thymic aging and extends organismal healthspan, dependent in part on expression of the FGF21 co-receptor β-klotho on thymic epithelial cells.
Paracrine FGF21 dynamically modulates mTOR signaling to regulate thymus function across the lifespan
Authors: Sarah A. Wedemeyer, Nicholas E. Jones, Iwan G. A. Raza, Freedom M. Green, Yangming Xiao, Manpreet K. Semwal, Aaron K. Garza, Kahealani S. Archuleta, Kymberly L. Wimberly, Thomas Venables, Georg A. Holländer, Ann V. Griffith
Journal: Nature Aging (2025)
Developmentally distinct architectures in top–down pathways controlling threat avoidance
Authors: Cassandra B. Klune, Caitlin M. Goodpaster, Michael W. Gongwer, Christopher J. Gabriel, Jennifer An, Rita Chen, Nico S. Jones, Owen H. Williams, Meelan Shari, Makayla Ramirez, Aliza Hacking, Timothy Andrade, Lindsay A. Schwarz, Laura A. DeNardo
Journal: Nature Neuroscience (2025)
Integrating the environmental and genetic architectures of aging and mortality
Authors: M. Austin Argentieri, Najaf Amin, Alejo J. Nevado-Holgado, William Sproviero, Jennifer A. Collister, Sarai M. Keestra, Midas M. Kuilman, Bigina N. R. Ginos, Mohsen Ghanbari, Aiden Doherty, David J. Hunter, Alexandra Alvergne, Cornelia M. van Duijn
Journal: Nature Medicine (2025)
Prognostic Relevance of Type 4a Myocardial Infarction and Periprocedural Myocardial Injury in Patients With Non–ST-Segment–Elevation Myocardial Infarction
Authors: Matteo Armillotta, Luca Bergamaschi, Pasquale Paolisso, Marta Belmonte, Francesco Angeli, Angelo Sansonetti, Andrea Stefanizzi, Davide Bertolini, Francesca Bodega, Sara Amicone, Lisa Canton, Damiano Fedele, Nicole Suma, Andrea Impellizzeri, Francesco Pio Tattilo, Daniele Cavallo, Ornella Di Iuorio, Khrystyna Ryabenko, Andrea Rinaldi, Gabriele Ghetti, Francesco Saia, Cinzia Marrozzini, Gianni Casella, Paola Rucci, Alberto Foà, Carmine Pizzi
Journal: Circulation (2025)

BACKGROUND: Periprocedural myocardial injury (PMI) with or without type 4a myocardial infarction (MI) might occur in patients with non–ST-segment–elevation MI (NSTEMI) after percutaneous coronary intervention (PCI). This study investigated the incidence and prognostic relevance of these events, according to current definitions, in patients with NSTEMI undergoing PCI. The best cardiac troponin I (cTnI) threshold of PMI for prognostic stratification is also suggested. METHODS: Consecutive patients with NSTEMI from January 2017 to April 2022 undergoing PCI with stable or falling pre-PCI cTnI levels were enrolled. According to the Fourth Universal Definition of Myocardial Infarction, the study population was stratified into those experiencing (1) PMI with type 4a MI, (2) PMI without type 4a MI, or (3) no PMI. Post-PCI cTnI increase &gt;20% with an absolute postprocedural value of ≥5 times the 99th percentile upper reference limit within 48 hours after PCI was used to define PMI. The primary end point was 1-year all-cause mortality, and the secondary end point consisted of major adverse cardiovascular events at 1 year, including all-cause mortality, nonfatal reinfarction, urgent revascularization, nonfatal ischemic stroke, and hospitalization for heart failure. Internal validation was performed in patients enrolled between May 2022 and April 2023. RESULTS: Among 1412 patients with NSTEMI undergoing PCI with stable or falling cTnI levels at baseline, 240 (17%) experienced PMI with type 4a MI, 288 (20.4%) experienced PMI without type 4a MI, and 884 (62.6%) experienced no PMI. PMI was associated with an increased risk of adverse clinical outcomes, with patients with type 4a MI demonstrating the highest rates of 1-year all-cause mortality and major adverse cardiovascular events. A post-PCI ΔcTnI &gt;20% but ≤40% showed similar outcomes to patients without PMI, whereas &gt;40% was identified as the optimal threshold for prognostically relevant PMI, confirmed in an internal validation cohort of 305 patients. CONCLUSIONS: Periprocedural ischemic events were frequent in patients with NSTEMI undergoing PCI with prognostic implications. A post-PCI ΔcTnI &gt;40%, combined with an absolute postprocedural value of ≥5 times the 99th percentile upper reference limit, was identified as the optimal threshold for diagnosing prognostically relevant PMI. Recognizing these events may improve risk stratification and management of patients with NSTEMI.
Dried blood spot testing versus standard i.v. sampling for GFR measurement with iohexol or 99mTc-DTPA
Authors: Morten Baltzer Houlind, Louise Westberg Strejby Christensen, Rikke Lundsgaard Nielsen, Aino Leegaard Andersen, Esben Iversen, Izzet Altintas, Olivia Bornæs, Ida Klitzing Storgaard, Helle Gybel Juul-Larsen, Baker Nawfal Jawad, Marya Morevati, Trine Meldgaard Lund, Ove Andersen, Morten Damgaard, Mads Hornum
Journal: Kidney International (2025)
Are your kidneys Ok? Detect early to protect kidney health
Authors: Joseph A Vassalotti, Anna Francis, Augusto Cesar Soares Dos Santos, Ricardo Correa-Rotter, Dina Abdellatif, Li-Li Hsiao, Stefanos Roumeliotis, Agnes Haris, Latha A Kumaraswami, Siu-Fai Lui, Alessandro Balducci, Vassilios Liakopoulos
Journal: Kidney International (2025)
Taxifolin attenuates liver fibrosis by regulating the phosphorylation of NDRG1 at Thr328 via hepatocyte-stellate cell cross talk
Authors: Chuan Ding, Zeping Wang, Kao Shi, Sunan Li, Xinyue Dou, Yan Ning, Gang Cheng, Qiao Yang, Xianan Sang, Mengyun Peng, Qiang Lyu, Lu Wang, Xin Han, Gang Cao
Journal: Acta Pharmaceutica Sinica B (2025)
A Tumor Heterogeneity-Independent Antigen-Responsive Nanocarrier Enabled by Bioorthogonal Pre-Targeting and Click-Activated Self-Immolative Polymer
Authors: Ye Liu, Qingyu Zong, Yalan Tu, Xingzu Zhang, Qiaoling Tan, Ihsan Ullah, Youyong Yuan
Journal: Biomaterials (2025)