tbuckley/cabot-search huggingface dataset:
Olaparib, temozolomide and concomitant radiotherapy for partially or biopsy-only glioblastoma first-line treatment: results from the OLA-TMZ-RTE-01 phase 1 study
Authors: Dinu Stefan, Paul Lesueur, Justine Lequesne, Loic Feuvret, Charlotte Bronnimann, Marie Castéra, Pierre-Emmanuel Brachet, Ioana Hrab, Mathilde Ducloie, Joëlle Lacroix, Marie Lecornu, Grégoire Braux, François Christy, Marie-Pierre Sunyach, Elizabeth Cohen-Jonathan Moyal, William Kao, Maxime Faisant, Evelyne Emery, Jean-Michel Grellard, Francois Sichel, Carine Laurent, Maxime Fontanilles, Bénédicte Clarisse
Journal: Clinical Cancer Research (2025)

Abstract Background: Radio-chemotherapy remains the mainstay of glioblastoma first-line treatment after extended surgery, but the prognosis is still poor. PARP inhibitors like olaparib may improve glioblastoma outcomes. We implemented a phase 1-2a trial to assess the safety and efficacy of olaparib combined with standard radio-chemotherapy as a first-line treatment in unresected glioblastoma patients. We herein present results of phase 1. Methods: Based on the Stupp regimen, two sequential dose escalations of olaparib were performed to distinguish the radiotherapy period and the maintenance period for assessing the maximum tolerated dose (MTD) of olaparib separately for each treatment period. Dose escalations were performed by a TITE-CRM (TIme-To-Event Continual Reassessment Method). Results: A total of 30 pts were enrolled: 20 (66.7%) men, median age 59 years [range 25-70], 12 (42.9%) Eastern Cooperative Oncology Group (ECOG) performance status of 0. Among them, 16 and 11 pts were assessable for determining MTD in each period. Hematological dose-limiting toxicities were experienced by 4 and 1 patients in each sequential dose escalation, respectively. MTD was olaparib 100 mg twice daily for 3 days a week in concomitant during both the radio-chemotherapy and maintenance periods of the standard treatment. Median progression-free and overall survival was 6.2 and 19.8 months, respectively. The 2-year survival rate was 36.7% [22.9-58.7]. Conclusions: Intermittent dosing of olaparib at radiosensitizing concentrations in concomitant with the Stupp protocol has an acceptable safety profile with promising outcomes in unresectable glioblastoma patients. Further efficacy determination is ongoing in the phase 2a step.
Targeting ABCD1-ACOX1-MET/IGF1R axis suppresses multiple myeloma
Authors: Zhannan Han, Zhibo Yan, Zhehan Ma, Yihui Wang, Maja Beus, Junqi Lu, Loren B. Weidenhammer, Kiran Lakhani, Jingyun Lee, John D. Civils, Cristina M. Furdui, Liang Liu, Jian Wu, Yubin Kang, Erhard Bieberich, Lawrence H. Boise, Mikhail A. Nikiforov
Journal: Leukemia (2025)
Fungal-derived tRNAs are expressed and aminoacylated in orchid mitochondria
Authors: Jessica M Warren, Luis F Ceriotti, M Virginia Sanchez-Puerta, Daniel B Sloan
Journal: Molecular Biology and Evolution (2025)

Abstract Plant mitochondrial genomes (mitogenomes) experience remarkable levels of horizontal gene transfer (HGT), including the recent discovery that orchids anciently acquired DNA from fungal mitogenomes. Thus far, however, there is no evidence that any of the genes from this interkingdom HGT are functional in orchid mitogenomes. Here, we applied a specialized sequencing approach to the orchid Corallorhiza maculata and found that some fungal-derived tRNA genes in the transferred region are transcribed, post-transcriptionally modified, and aminoacylated. In contrast, all the transferred protein-coding sequences appear to be pseudogenes. These findings show that fungal HGT has altered the composition of the orchid mitochondrial tRNA pool and suggest that these foreign tRNAs function in translation. The exceptional capacity of tRNAs for HGT and functional replacement is further illustrated by the diversity of tRNA genes in the C. maculata mitogenome, which also include genes of plastid and bacterial origin in addition to their native mitochondrial counterparts.
President Trump wants an alternative to the World Health Organization: how should we respond?
Authors: Kent Buse, Christina Pagel, Adeeba Kamarulzaman, Martin McKee
Journal: BMJ (2025)

Much attention has rightly been placed on how to fill the World Health Organization's funding gap if and when the US withdraws. Kent Buse and colleagues argue that President Trump's idea to establish a parallel structure is equally insidious as withdrawing from WHO
Dichotomous <scp>STAT5</scp> and <scp>STAT6</scp> Activation in T Cells Reflects Cytokine Shifts Between Blood and Skin in Atopic Dermatitis
Authors: Andreas Boldt, Regina Treudler, Marie Rabe, Niklas Artz, Sabine Seiffert, Rachael Bogle, Xianying Xing, Louise Wilkens, Ariane Bialas, Lea Präger, Lam C. Tsoi, Ulrike Koehl, Sandra Franz, Sonja Grunewald, Jan C. Simon, J. Michelle Kahlenberg, Johann E. Gudjonsson, Benjamin Klein
Journal: Allergy (2025)

We assessed STAT activation in T cells in blood and skin of AD patients versus HC. pSTAT5+ T cells were increased in AD blood, correlated with disease activity, and were induced by common γc cytokines. Skin T cells exhibited a STAT6 signature, whereas only a subset was positive for STAT5. AD, atopic dermatitis; HC, healthy controls; STAT: Signal Transducers and Activators of Transcription. The data that support the findings of this study are available from the corresponding author upon reasonable request. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Radioresistance in rectal cancer: can nanoparticles turn the tide?
Authors: Diogo Coelho, Diogo Estêvão, Maria José Oliveira, Bruno Sarmento
Journal: Molecular Cancer (2025)

Abstract Rectal cancer accounts for over 35% of the worldwide colorectal cancer burden representing a distinctive subset of cancers from those arising in the colon. Colorectal cancers exhibit a continuum of traits that differ with their location in the large intestine. Due to anatomical and molecular differences, rectal cancer is treated differently from colon cancer, with neoadjuvant chemoradiotherapy playing a pivotal role in the control of the locally advanced disease. However, radioresistance remains a major obstacle often correlated with poor prognosis. Multifunctional nanomedicines offer a promising approach to improve radiotherapy response rates, as well as to increase the intratumoral concentration of chemotherapeutic agents, such as 5-Fluorouracil. Here, we revise the main molecular differences between rectal and colon tumors, exploring the complex orchestration beyond rectal cancer radioresistance and the most promising nanomedicines reported in the literature to improve neoadjuvant therapy response rates. Graphical Abstract
Dirt Under the Finger‐Nails—More Malignant Than Malignancy
Authors: Sumeet Mirgh, Sujata Lall, Sachin Punatar, Anant Gokarn, Nishant Jindal, Akanksha Chichra, Vivek Bhat, Navin Khattry
Journal: American Journal of Hematology (2025)

A young boy developed steroid refractory GVHD post haploidentical transplant for relapsed B-ALL. He was on systemic immunosuppression with two immunosuppressants, and had history of CMV reactivation and tuberculosis. Eight months post-transplant, he was hospitalized with multi-drug-resistant gram-negative sepsis, and during the same episode, he developed penile lesions which progressed to dry gangrene of glans-penis. Fusarium grew in blood and penile lesions. On retrospective thinking, it was discerned that his onychomycoses were the probable cause of his penile lesions with hematogenous dissemination, as nails also grew Fusarium. This case highlights the need for a vigilant skin and nail examination in immunocompromised patients. This is important for two perspectives. First, cultures from potential colonized sources can help early identification and escalation of treatment. Secondly, appropriate precautions and treatment of superficial infections can help prevent dissemination. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Association of Sleep Traits With Venous Thromboembolism: Prospective Cohort and Mendelian Randomization Studies
Authors: Yuqian Li, Feifei Sun, Chao Ji, Honghao Yang, Zheng Ma, Yuhong Zhao, Zhiying Zhao, Yang Xia
Journal: American Journal of Hematology (2025)

ABSTRACT Previous research indicates an association between sleep traits and venous thromboembolism (VTE) risk, though causal relationships remain uncertain. This study evaluated combined and independent associations between sleep traits and VTE risk using UK Biobank data and explored the causal associations between sleep traits and VTE through two‐sample Mendelian randomization (MR) analyses. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations between the healthy sleep score, as well as individual sleep traits (including sleep duration, insomnia, daytime sleepiness, snoring, and chronotype), and VTE risk were calculated using Cox proportional hazards regression models. Additionally, the two‐sample MR analyses used the inverse‐variance weighted method to determine odds ratios (ORs) and 95% CIs for causal associations. In the cohort analysis, 314 077 VTE–free participants were followed for a median of 12.3 years, during which 7176 VTE cases occurred. In comparison to those with a sleep score of 0–1, participants with a score of 5 were associated with a 30% lower risk of VTE (HR: 0.70; 95% CI: 0.61–0.80). A U‐shaped association was noted between sleep duration and VTE risk. Both short (≤ 6 h) and long (≥ 9 h) sleep durations increased VTE risk. Excessive daytime sleepiness, snoring, and evening chronotype also elevated VTE risk. MR analyses supported a causal relationship for short sleep duration (OR: 1.24; 95% CI: 1.04–1.47) with VTE risk, while other sleep traits showed no causal association. These findings underscore the importance of optimal sleep in reducing VTE risk.
Intricate interplay of CRISPR-Cas systems, anti-CRISPR proteins, and antimicrobial resistance genes in a globally successful multi-drug resistant Klebsiella pneumoniae clone
Authors: Jianping Jiang, Astrid V Cienfuegos-Galletd, Tengfei Long, Gisele Peirano, Tingyu Chu, Johann D D Pitout, Barry N Kreiswirth, Liang Chen
Journal: Genome Medicine (2025)
A machine learning decision support tool optimizes WGS utilization in a neonatal intensive care unit
Authors: Edwin F. Juarez, Bennet Peterson, Erica Sanford Kobayashi, Sheldon Gilmer, Laura E. Tobin, Brandan Schultz, Jerica Lenberg, Jeanne Carroll, Shiyu Bai-Tong, Nathaly M. Sweeney, Curtis Beebe, Lawrence Stewart, Lauren Olsen, Julie Reinke, Elizabeth A. Kiernan, Rebecca Reimers, Kristen Wigby, Chris Tackaberry, Mark Yandell, Charlotte Hobbs, Matthew N. Bainbridge
Journal: npj Digital Medicine (2025)

The Mendelian Phenotype Search Engine (MPSE), a clinical decision support tool using Natural Language Processing and Machine Learning, helped neonatologists expedite decisions to whole genome sequencing (WGS) to diagnose patients in the neonatal intensive care unit. After the MPSE was introduced, utilization of WGS increased, time to ordering WGS decreased, and WGS diagnostic yield increased.
The role of the early-life gut microbiome in childhood asthma
Authors: Ulrika Boulund, Jonathan Thorsen, Urvish Trivedi, Kaare Tranæs, Jie Jiang, Shiraz A. Shah, Jakob Stokholm
Journal: Gut Microbes (2025)

Asthma is a chronic disease affecting millions of children worldwide, and in severe cases requires hospitalization. The etiology of asthma is multifactorial, caused by both genetic and environmental factors. In recent years, the role of the early-life gut microbiome in relation to asthma has become apparent, supported by an increasing number of population studies, in vivo research, and intervention trials. Numerous early-life factors, which for decades have been associated with the risk of developing childhood asthma, are now being linked to the disease through alterations of the gut microbiome. These factors include cesarean birth, antibiotic use, breastfeeding, and having siblings or pets, among others. Association studies have highlighted several specific microbes that are altered in children developing asthma, but these can vary between studies and disease phenotype. This demonstrates the importance of the gut microbial ecosystem in asthma, and the necessity of well-designed studies to validate the underlying mechanisms and guide future clinical applications. In this review, we examine the current literature on the role of the gut microbiome in childhood asthma and identify research gaps to allow for future microbial-focused therapeutic applications in asthma.
Decoding pan-cancer treatment outcomes using multimodal real-world data and explainable artificial intelligence
Authors: Julius Keyl, Philipp Keyl, Grégoire Montavon, René Hosch, Alexander Brehmer, Liliana Mochmann, Philipp Jurmeister, Gabriel Dernbach, Moon Kim, Sven Koitka, Sebastian Bauer, Nikolaos Bechrakis, Michael Forsting, Dagmar Führer-Sakel, Martin Glas, Viktor Grünwald, Boris Hadaschik, Johannes Haubold, Ken Herrmann, Stefan Kasper, Rainer Kimmig, Stephan Lang, Tienush Rassaf, Alexander Roesch, Dirk Schadendorf, Jens T. Siveke, Martin Stuschke, Ulrich Sure, Matthias Totzeck, Anja Welt, Marcel Wiesweg, Hideo A. Baba, Felix Nensa, Jan Egger, Klaus-Robert Müller, Martin Schuler, Frederick Klauschen, Jens Kleesiek
Journal: Nature Cancer (2025)

Abstract Despite advances in precision oncology, clinical decision-making still relies on limited variables and expert knowledge. To address this limitation, we combined multimodal real-world data and explainable artificial intelligence (xAI) to introduce AI-derived (AID) markers for clinical decision support. We used xAI to decode the outcome of 15,726 patients across 38 solid cancer entities based on 350 markers, including clinical records, image-derived body compositions, and mutational tumor profiles. xAI determined the prognostic contribution of each clinical marker at the patient level and identified 114 key markers that accounted for 90% of the neural network’s decision process. Moreover, xAI enabled us to uncover 1,373 prognostic interactions between markers. Our approach was validated in an independent cohort of 3,288 patients with lung cancer from a US nationwide electronic health record-derived database. These results show the potential of xAI to transform the assessment of clinical variables and enable personalized, data-driven cancer care.
Plasma proteomic evidence for increased β-amyloid pathology after SARS-CoV-2 infection
Authors: Eugene P. Duff, Henrik Zetterberg, Amanda Heslegrave, Abbas Dehghan, Paul Elliott, Naomi Allen, Heiko Runz, Rhiannon Laban, Elena Veleva, Christopher D. Whelan, Benjamin B. Sun, Paul M. Matthews
Journal: Nature Medicine (2025)

Abstract Previous studies have suggested that systemic viral infections may increase risks of dementia. Whether this holds true for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infections is unknown. Determining this is important for anticipating the potential future incidence of dementia. To begin to do this, we measured plasma biomarkers linked to Alzheimer’s disease pathology in the UK Biobank before and after serology-confirmed SARS-CoV-2 infections. SARS-CoV-2 infection was associated with biomarkers associated with β-amyloid pathology: reduced plasma Aβ42:Aβ40 ratio and, in more vulnerable participants, lower plasma Aβ42 and higher plasma pTau-181. The plasma biomarker changes were greater in participants who had been hospitalized with COVID-19 or had reported hypertension previously. We showed that the changes in biomarkers were linked to brain structural imaging patterns associated with Alzheimer’s disease, lower cognitive test scores and poorer overall health evaluations. Our data from this post hoc case–control matched study thus provide observational biomarker evidence that SARS-CoV-2 infection can be associated with greater brain β-amyloid pathology in older adults. While these results do not establish causality, they suggest that SARS-CoV-2 (and possibly other systemic inflammatory diseases) may increase the risk of future Alzheimer’s disease.
Foot Infection of Mycobacterium smegmatis
Authors: Liheng Zheng, Xiaojin Liu, Huifen Zuo, Jiahao Hao, Minghui Song, Jiaqing Ye, Cuiying Zheng, Zhongjun Feng, Yan Zhao, Zhenjun Zhao, Lijie Zhang
Journal: Clinical Microbiology and Infection (2025)
The assessment of gastrointestinal transit by the Atmo Capsule: A comparison with the SmartPill Capsule
Authors: Braden Kuo, Allen A Lee, Thomas Abell, Ashok Attaluri, Michael Cline, William Hasler, Vincent Ho, Anthony Lembo, Amir Masoud, Richard McCallum, Baharak Moshiree, Eamonn Mm Quigley, Satish Sc Rao, Abigail Stocker, Mayra Sanchez, Irene Sarosiek, Brian Surjanhata, Jerry Zhou, William D Chey
Journal: Clinical Gastroenterology and Hepatology (2025)
A high-performance chitosan-grafted Cu(Ⅱ) coating improves endothelialization and mitigates the degradation of biodegradable magnesium alloy stents
Authors: Pengyu Li, Xun Qi, Dexiao Liu, Jing Ma, Shaogang Wang, Ke Yang, Wenhua Yan, Shanshan Chen
Journal: Biomaterials (2025)
Mitochondria‐targeting Bimetallic Cluster Nanozymes Alleviate Neuropathic Pain Through Scavenging ROS and Reducing Inflammation
Authors: Xiaolei Cheng, Tianjiao Xia, Min Han, Minhui Xu, Weining Yuan, Ziqi Wei, Wei Jiang, Hao Tang, Qian Bai, Xiaoping Gu
Journal: Advanced Healthcare Materials (2025)

Abstract Neuropathic pain is a significant public health concern. Inflammatory mediators and reactive oxygen species (ROS) are recognized as primary contributors to pain perception. In this study, a mitochondria‐targeted modification of bimetallic cluster nanozyme (TPP‐Au‐Ru) is developed. This TPP‐Au‐Ru nanozyme exhibits a high affinity for the mitochondrial matrix, effectively scavenging ROS and attenuating inflammatory mediators in both in vitro and in vivo settings. Additionally, the nanozyme inhibits the activation of the MAPK and NF‐κB signaling cascades and protect mitochondrial function. Furthermore, a therapeutic dose of the TPP‐Au‐Ru nanozyme is able to alleviate nociceptive symptoms for up to 36 h with minimal biological toxicity. Therefore, the sustained mitochondrial delivery of TPP‐Au‐Ru nanozyme provides an effective and long‐lasting approach to neuropathic pain. This innovative approach shows promise for the development of more efficient therapeutic interventions, potentially revolutionizing the management of neuropathic pain and enhancing the quality of life for affected individuals.
Inhibition of macrophage inflammasome assembly and pyroptosis with GC-1 ameliorates acute lung injury
Authors: Bin Li, Jingyi Liu, Wanyu He, Yanlin Zhou, Man Zhao, Cong Xia, Xiaoyue Pan, Zhihua Ji, Ruoyu Duan, Hui Lian, Kai Xu, Guoying Yu, Lan Wang
Journal: Theranostics (2025)

Rationale: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a critical syndrome with a mortality rate of up to 40%, and it is characterized by a prominent inflammatory cascade. The inflammasome and pyroptosis play crucial regulatory roles in regulating various inflammatory-related diseases by serving as pivotal signaling platforms for inflammatory responses and mediating the release of substantial quantities of inflammatory factors. Our previous studies confirmed that GC-1, a clinical-stage thyroid hormone analog, effectively mitigated pulmonary fibrosis by restoring mitochondrial function in epithelial cells. However, the potential effects of GC-1 on macrophage inflammasome assembly and pyroptosis in lung injury as well as the underlying mechanisms, remain unclear. Methods: The effects of GC-1 on lung injury, oxidative damage and inflammation were evaluated in two murine models of ALI (LPS- or HCl-induced models) by assessing lung pathology, the concentrations of IL-1β and IL-18 in BAL fluid, inflammasome and the levels of inflammasome- and pyroptosis-related proteins. Additionally, the impact of GC-1 on ROS-mediated inflammasome assembly and pyroptosis was investigated by examining ROS levels, Nrf2 signaling, and inflammasome adaptor protein ASC levels in mouse alveolar macrophages and human THP-1 macrophages treated with LPS and ATP. The Nrf2 inhibitor ML385 and the mitochondrial-ROS inhibitor Mito-TEMPO were used to further elucidate the effect of GC-1 on the Nrf2-p53-ASC pathway. Results: GC-1 significantly alleviated inflammation and lung injury in ALI model mice, as indicated by pulmonary pathology, inflammatory cytokine levels, ROS production and pyroptosis rates. Consistently, GC-1 inhibited ASC recruitment and oligomerization in macrophages, which suppressed the gasdermin D-mediated release of IL-1β and IL-18. These findings indicated a reduction in inflammasome assembly and pyroptosis initiation. Further research revealed that GC-1 may mitigate oxidative stress induced by mitochondrial damage through Nrf2 signaling, thereby inhibiting the expression of ROS-activated p53 and the target gene ASC. This protective effect of GC-1 could be reversed by ML385 and mimicked by Mito-TEMPO. Conclusions: This study presents a novel mechanism for treating ALI in which GC-1 inhibits macrophage ROS-mediated inflammasome assembly and pyroptosis through Nrf2-p53-ASC pathway. These findings highlight the promising potential of the use of GC-1 as an anti-inflammatory and antioxidant drug in the treatment of ALI/ARDS.
Calnexin promotes glioblastoma progression by inducing protective mitophagy through the MEK/ERK/BNIP3 pathway
Authors: Xuchen Liu, Jiangli Zhao, Qingyuan Sun, Zhiwei Xue, Ziyi Tang, Wenyu Liu, Junzhi Liu, Baojian Miao, Nan Su, Yanya He, Yuehua Zhu, Bin Huang, Ning Yang, Chao Li, Jiwei Wang, Xinyu Wang
Journal: Theranostics (2025)

Rationale: Glioblastoma multiforme (GBM), one of the most malignant tumors of the central nervous system, has a poor prognosis, mainly because of its high recurrence caused by the rapid development of drug resistance to postoperative chemotherapy. Although macroautophagy/autophagy is believed to be a fundamental factor in tumor survival during chemotherapy, there is still a lack of autophagy biomarkers for predicting patient prognosis and chemotherapeutic efficacy in clinical practice. Methods: We combined transcriptomic and single-cell sequencing data to identify differentially expressed autophagy-related genes in gliomas. Overexpression of calnexin (CANX), a key gene related to protein folding, and its secretion in the endoplasmic reticulum (ER) was identified, suggesting poor prognosis in GBM patients. The autophagy flow related to CANX was detected by transmission electron microscopy (TEM), Western blotting, and immunofluorescence. Flow cytometry, cell proliferation, activity assays, and the GBM intracranial xenograft mouse model were employed to validate CANX's role in GBM progression. Results: CANX knockdown inhibited proliferation and autophagosome formation in GBM cells. On the other hand, CANX overexpression increased mitogen-activated protein kinase (MAPK) activity, leading to the accumulation of BNIP3 (CL2/adenovirus E1B 19 kDa interacting protein 3, a critical factor regulating mitophagy) and protective mitophagy. Notably, when combined with temozolomide (TMZ), CANX knockdown extended the lifespan of GBM-bearing mice. Additionally, our studies revealed that the classic calcium inhibitor nimodipine (ND) decreased CANX expression and thus enhanced the sensitivity to TMZ. Conclusions: Our findings indicate that CANX functions as an oncogene in GBM. We also characterize the CANX/MEK/ERK/BNIP3 mitophagy pathway, provide new insights into the molecular mechanism of GBM drug resistance, and identify a therapeutic target.