tbuckley/cabot-search huggingface dataset:
Dual‐Functional Hafnium Oxide Nanoplatform Combining High‐Z Radiosensitization With Bcl‐2 Gene Silencing for Enhanced Cancer Radiotherapy
Authors: Seungyong Shin, Ga‐Hyun Bae, Jun‐Hyeok Han, Ha Eun Shin, Joo Dong Park, Seunghyo Ko, Eun‐Young Koh, Jieun Han, Su Chul Han, Jason Joon Bock Lee, Dong‐Hyun Kim, Heerim Nam, Wooram Park
Journal: Advanced Healthcare Materials (2025)

Abstract The efficacy of radiotherapy is often limited by insufficient radiosensitization and tumor radioresistance. This study reports a dual‐functional hafnium oxide nanoplatform that combines high‐Z radiosensitization with Bcl‐2 gene silencing for enhanced cancer radiotherapy. The nanoplatform is developed by surface modification of hafnium oxide nanoparticles with polyethyleneimine, enabling efficient siRNA delivery while maintaining inherent high‐Z radiosensitizing properties. Comprehensive physicochemical characterization confirmed the successful surface modification and stable siRNA complexation. Upon radiation exposure, the nanoplatform enhanced reactive oxygen species generation and DNA damage while simultaneously delivering Bcl‐2 siRNA to suppress radioresistance mechanisms. In vitro studies revealed significant enhancement of radiation‐induced cell death through synergistic effects of high‐Z radiosensitization and Bcl‐2 silencing, evidenced by increased γ‐H2AX expression and apoptotic cell population. In a murine colon cancer model, the nanoplatform achieved remarkable tumor growth inhibition (80%) when combined with radiotherapy while exhibiting favorable biocompatibility in major organs. Mechanistic studies confirmed effective Bcl‐2 downregulation and enhanced DNA damage in tumor tissues, validating this dual‐functional therapeutic approach. This study presents a promising strategy for improving radiotherapy outcomes through the simultaneous enhancement of radiosensitization and suppression of radioresistance, potentially advancing the field of cancer radiotherapy.
Beyond First-Generation KRAS Inhibitors: BBO-8520 Tests the Dual Mechanism Hypothesis
Authors: Zhiwei Zhou, Kenneth D. Westover
Journal: Cancer Discovery (2025)

This issue highlights the development of a first-in-class small-molecule covalent KRASG12C inhibitor, BBO-8520, which targets both the active (ON) and inactive (OFF) states of KRAS. This dual-state targeting offers a significant opportunity to overcome the resistance mechanisms that have limited the efficacy of first-generation KRAS inhibitors and addresses critical challenges in KRAS-targeted therapy. See related article by Maciag et al., p. 578.
Genomic insights into the plasmidome of non-tuberculous mycobacteria
Authors: Margo Diricks, Florian P. Maurer, Viola Dreyer, Ivan Barilar, Christian Utpatel, Matthias Merker, Nils Wetzstein, Stefan Niemann
Journal: Genome Medicine (2025)

Non-tuberculous mycobacteria (NTM) are a diverse group of environmental bacteria that are increasingly associated with human infections and difficult to treat. Plasmids, which might carry resistance and virulence factors, remain largely unexplored in NTM. We used publicly available complete genome sequence data of 328 NTM isolates belonging to 125 species to study gene content, genomic diversity, and clusters of 196 annotated NTM plasmids. Furthermore, we analyzed 3755 draft genome assemblies from over 200 NTM species and 5415 short-read sequence datasets from six clinically relevant NTM species or complexes including M. abscessus, M. avium complex, M. ulcerans complex and M. kansasii complex, for the presence of these plasmids. Between one and five plasmids were present in approximately one-third of the complete NTM genomes. The annotated plasmids varied widely in length (most between 10 and 400 kbp) and gene content, with many genes having an unknown function. Predicted gene functions primarily involved plasmid replication, segregation, maintenance, and mobility. Only a few plasmids contained predicted genes that are known to confer resistance to antibiotics commonly used to treat NTM infections. Out of 196 annotated plasmid sequences, 116 could be grouped into 31 clusters of closely related sequences, and about one-third were found across multiple NTM species. Among clinically relevant NTM, the presence of NTM plasmids showed significant variation between species, within (sub)species, and even among strains within (sub)lineages, such as dominant circulating clones of Mycobacterium abscessus. Our analysis demonstrates that plasmids are a diverse and heterogeneously distributed feature in NTM bacteria. The frequent occurrence of closely related putative plasmid sequences across different NTM species suggests they may play a significant role in NTM evolution through horizontal gene transfer at least in some groups of NTM. However, further in vitro investigations and access to more complete genomes are necessary to validate our findings, elucidate gene functions, identify novel plasmids, and comprehensively assess the role of plasmids in NTM.
Dexamethasone for the management of CRS Related to teclistamab in patients with relapsed/refractory multiple myeloma
Authors: James A. Davis, Jordan Snyder, Mikhaila Rice, Donald C. Moore, Christopher Cahoon, Kelley Julian, Charlotte B. Wagner, Katelynn Granger, Kimberly M. Green, Shebli Atrash, Hailey Hill, Jessica McElwee, Grace Elsey, Jack Khouri, Joslyn Rudoni, Zahra Mahmoudjafari, Victoria R. Nachar
Journal: Blood Cancer Journal (2025)
Highlighted Research Articles
Journal: Cancer Discovery (2025)

In This Issue| March 03 2025 Highlighted Research Articles Author & Article Information Online ISSN: 2159-8290 Print ISSN: 2159-8274 ©2025 American Association for Cancer Research2025American Association for Cancer Research Cancer Discov (2025) 15 (3): 449–451. https://doi.org/10.1158/2159-8290.CD-15-3-ITI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record March 3 2025 Citation Highlighted Research Articles. Cancer Discov 1 March 2025; 15 (3): 449–451. https://doi.org/10.1158/2159-8290.CD-15-3-ITI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Downregulation of the major histocompatibility complex class I (MHCI) is a mechanism of immune evasion associated with immune-cold tumors, like prostate cancer. Chesner and colleagues conducted a genome-wide CRISPR screen to identify regulators of MHCI in prostate cancer and found that the androgen receptor (AR) was a dominant repressor of MHCI. This observation was validated in vitro with small molecule inhibitors, in vivo with genetic knockdown experiments, and confirmed in multiple clinical trial datasets. Together, these data identify AR as a repressor of MHCI in prostate cancer with implications for new immunotherapy trials in this disease. See article, p. 481. Biomarkers of response to immunotherapies in hepatocellular carcinoma (HCC) are missing, highlighting the urgent need to improve patient selection and identify novel combination therapies that restore response in resistant patients. Lindblad and colleagues identified activation of NOTCH1, an understudied oncogene in HCC, as a driver of immunotherapy resistance in... You do not currently have access to this content.
Effectiveness Of Sports Activity To Improve Motor Coordination In Special Children With Obesity.
Authors: Thirukumara Mahendran T, , Dr.M.Arun kumar
Journal: British Journal of Sports Medicine (2019)

Background: Obesity is a complex and multifaceted condition characterized by an excessive accumulation of body fat, which can negatively affect health. Objectives: This study aims to evaluate the effectiveness of sports activities in enhancing motor coordination among children with obesity and special needs. Materials And Methods: A research design involving screening, assessment, and intervention was used. The sample size was determined based on inclusion and exclusion criteria, and motor coordination was assessed using various scales. The study was conducted within a specified duration following a structured procedure. Results: The findings suggest that engaging in sports activities significantly improves motor coordination among children with obesity and special needs. Conclusion: Sports interventions are an effective approach for improving motor skills in children with obesity and special needs.
Plant cell-cycle regulators control the nuclear environment for viral pathogenesis
Authors: Xu Zhang, Ge Wang, Peng Zhang, Chunyan Chen, Jiucheng Zhang, Yumei Bian, Minmin Liu, Chenxu Niu, Fengze Sun, Yahui Wang, Genzhong Liu, Zhimin Wang, Fangfang Ma, Zhilong Bao
Journal: Cell Host & Microbe (2025)
A cellular and molecular basis of leptin resistance
Authors: Bowen Tan, Kristina Hedbacker, Leah Kelly, Zhaoyue Zhang, Alexandre Moura-Assis, Ji-Dung Luo, Joshua D. Rabinowitz, Jeffrey M. Friedman
Journal: Cell Metabolism (2025)

Similar to most humans with obesity, diet-induced obese (DIO) mice have high leptin levels and fail to respond to the exogenous hormone, suggesting that their obesity is caused by leptin resistance, the pathogenesis of which is unknown. We found that leptin treatment reduced plasma levels of leucine and methionine, mTOR-activating ligands, leading us to hypothesize that chronic mTOR activation might reduce leptin signaling. Rapamycin, an mTOR inhibitor, reduced fat mass and increased leptin sensitivity in DIO mice but not in mice with defects in leptin signaling. Rapamycin restored leptin's actions on POMC neurons and failed to reduce the weight of mice with defects in melanocortin signaling. mTOR activation in POMC neurons caused leptin resistance, whereas POMC-specific mutations in mTOR activators decreased weight gain of DIO mice. Thus, increased mTOR activity in POMC neurons is necessary and sufficient for the development of leptin resistance in DIO mice, establishing a key pathogenic mechanism leading to obesity.
A highland-adaptation variant near MCUR1 reduces its transcription and attenuates erythrogenesis in Tibetans
Authors: Jie Ping, Xinyi Liu, Yiming Lu, Cheng Quan, Pengcheng Fan, Hao Lu, Qi Li, Cuiling Wang, Zheng Zhang, Mengyu Liu, Shunqi Chen, Lingle Chang, Yuqing Jiang, Qilin Huang, Jie Liu, Tana Wuren, Huifang Liu, Ying Hao, Longli Kang, Guanjun Liu, Hui Lu, Xiaojun Wei, Yuting Wang, Yuanfeng Li, Hao Guo, Yongquan Cui, Haoxiang Zhang, Yang Zhang, Yujia Zhai, Yaoxi He, Wangshan Zheng, Xuebin Qi, None Ouzhuluobu, Huiping Ma, Linpeng Yang, Xin Wang, Wanjun Jin, Ying Cui, Rili Ge, Shizheng Wu, Yuan Wei, Bing Su, Fuchu He, Hongxing Zhang, Gangqiao Zhou
Journal: Cell Genomics (2025)

To identify genomic regions subject to positive selection that might contain genes involved in high-altitude adaptation (HAA), we performed a genome-wide scan by whole-genome sequencing of Tibetan highlanders and Han lowlanders. We revealed a collection of candidate genes located in 30 genomic loci under positive selection. Among them, MCUR1 at 6p23 was a novel pronounced candidate. By single-cell RNA sequencing and comprehensive functional studies, we demonstrated that MCUR1 depletion leads to impairment of erythropoiesis under hypoxia and normoxia. Mechanistically, MCUR1 knockdown reduced mitochondrial Ca2+ uptake and then concomitantly increased cytosolic Ca2+ levels, which thereby reduced erythropoiesis via the CAMKK2-AMPK-mTOR axis. Further, we revealed rs61644582 at 6p23 as an expression quantitative trait locus for MCUR1 and a functional variant that confers an allele-specific transcriptional regulation of MCUR1. Overall, MCUR1-mediated mitochondrial Ca2+ homeostasis is highlighted as a novel regulator of erythropoiesis, deepening our understanding of the genetic mechanism of HAA.
3D bioprinted functional scaffold based on synergistic induction of iprf and laponite exerts efficient and personalised bone regeneration via MiRNA-mediated TGF-β/Smads signaling
Authors: Bojun Cao, Kunqi Zhang, Rongtai Zuo, Zhiyang Kang, Jieming Lin, Zhixuan Kang, Dinghao Luo, Yimin Chai, Jia Xu, Qinglin Kang, Shuo Qiu
Journal: International Journal of Surgery (2025)

Background: Limited stem cells, low vascularization efficiency and weak osteoinductive activity plague the repair and reconstruction of bone defects with cell-free scaffolds. Methods: Herein, injectable platelet-rich fibrin (i-PRF) was loaded into a methacrylated alginate/gelatin-methylcellulose (AGM) bioink system and constructed a porous hydrogel scaffold by three-dimensional bioprinting. The addition of nanosilicate-laponite (Lap) further enhanced this scaffold and synergized with i-PRF to promote efficient and personalized cranial regeneration. Results: At the biochemical level, Lap significantly enhanced the ability of the scaffold to retard growth factor release, and multiple physiologically proportional growth factors in the scaffold synergistically promoted rapid neoangiogenesis and concomitantly recruited endogenous BMSCs. More importantly, the bioactive ions released by Lap markedly promoted the proliferation of BMSCs and consistently induced the osteogenic differentiation of BMSCs; At the immunological level, iPRF-AGM@Lap significantly attenuates the inflammatory response by promoting macrophage M2 polarization. Mechanistically, miRNA sequencing and functional validation experiments demonstrated that bioactive ions released by Lap could synergize with growth factors in iPRF to promote osteogenic differentiation of BMSC through the miR-21 and miR-125a-mediated TGF-β/Smads signaling pathway. Conclusion: The results of this study provide a new idea for the personalized treatment of bone defects.
Letter to the editor: the incidence and outcomes of hyperacute cardiovascular dysfunction following isolated traumatic brain injury: an observational cohort study
Authors: Yu Chang, Kuan-Yu Chi, Hany Atwan
Journal: International Journal of Surgery (2025)

aSection of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan bDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA cFaculty of Medicine, Assiut University, Assiut, Egypt *Corresponding author. Address: Faculty of Medicine, Assiut University, Assiut, Egypt, Tel: +201275639916, E-mail: [email protected] (H. Atwan). Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Improvement in dermatomyositis-associated muscle disease with anifrolumab
Authors: Leila H Shayegan, Katharina S Shaw, Ged G Wieschhoff, Nnenna Ezeh, Yoo Jung Kim, Neda Shahriari, Ellen E Anshelevich, Lorena A Acevedo, Avery LaChance, Fatma Dedeoglu, Rochelle L Castillo, Allen W Ho, Ruth Ann Vleugels
Journal: British Journal of Dermatology (2025)

We describe radiologic and symptomatic improvement in two dermatomyositis patients with recalcitrant muscle disease following off-label treatment with anifrolumab, a monoclonal antibody targeting type I IFN receptor recently approved by the FDA and EMA for the treatment of systemic lupus erythematosus.
Frequency and Clinical Significance of Clonal and Subclonal Driver Mutations in High-Risk Neuroblastoma at Diagnosis: A Children's Oncology Group Study
Authors: Esther R. Berko, Arlene Naranjo, Alexander A. Daniels, Samantha N. McNulty, Kateryna Krytska, Todd Druley, Kirstin Zelley, Balakrishna Koneru, Lulu Chen, Grace Polkosnik, Meredith S. Irwin, Rochelle Bagatell, John M. Maris, C. Patrick Reynolds, Steven G. DuBois, Julie R. Park, Yael P. Mossé
Journal: Journal of Clinical Oncology (2025)

Relapsed high-risk neuroblastomas (NBLs) are enriched for targetable mutations in ALK and RAS-MAPK pathways, yet the prognostic effect of these aberrations and relevance of subclonal mutations at diagnosis remain undefined. We describe the spectrum and clinical significance of clonal and subclonal pathogenic alterations in high-risk NBL. We developed a focused high-risk NBL sequencing panel including ALK, NRAS, KRAS, HRAS, BRAF, PTPN11, TP53, and ATRX genes for ultra-deep sequencing and applied this assay to 242 pretherapy tumors from patients enrolled on the phase III trial Children's Oncology Group ANBL0532. We assessed the effect of clonal and subclonal mutations on event-free survival (EFS) and overall survival (OS). ALK-activating mutations occurred in 21.5% of tumors (n = 52, 30 clonal, 22 subclonal), and 3.3% (n = 8) showed ALK amplification. EFS and OS for patients with any ALK-aberrant tumor were inferior to patients with wild-type (WT) ALK tumors (5-year OS 37.7% v 66.3%; hazard ratio [HR], 1.992; P = .0007). EFS and OS for patients with tumors harboring activating ALK mutations ≥5% variant allele frequency (VAF) were inferior to ALK WT (5-year OS 37.7% v 66.3%; HR, 1.966; P = .0041). The 5-year EFS and OS for patients with ALK-amplified tumors were 25.0%. RAS pathway mutations occurred in 7.9% of tumors (n = 19; four clonal, 15 subclonal), with EFS and OS for those with VAF ≥5% inferior to RAS-WT patients (5-year OS 19.1% v 60.0%; HR, 3.021; P = .0168). Ultra-deep sequencing of high-risk NBLs demonstrates that oncogenic aberrations are more prevalent at diagnosis than previously recognized. ALK and RAS pathway aberrations confer inferior outcomes in patients treated with contemporary therapy, emphasizing the need for novel therapeutic approaches.
Anti-senescence therapies: a new concept to address cardiovascular disease
Authors: Stevan D Stojanović, Thomas Thum, Johann Bauersachs
Journal: Cardiovascular Research (2025)

Accumulation of senescent cells is an increasingly recognized factor in the development and progression of cardiovascular disease. Senescent cells of different types display a pro-inflammatory and matrix remodeling molecular program, known as the 'senescence associated secretory phenotype' (SASP), which has roots in (epi)genetic changes. Multiple therapeutic options (senolytics, anti-SASP senomorphics and epigenetic reprogramming) that delete or ameliorate cellular senescence have recently emerged. Some drugs routinely used in the clinics also have anti-senescence effects. However, multiple challenges hinder the application of novel anti-senescence therapeutics in the clinical setting. Understanding the biology of cellular senescence, advantages and pitfalls of anti-senescence treatments, as well as patients that can profit from these interventions is necessary to introduce this novel therapeutic modality into the clinics. We provide a guide through the molecular machinery of senescent cells, systematize anti-senescence treatments and propose a pathway towards senescence-adapted clinical trial design to aid future efforts.
A comparative assessment of self-limiting genetic control strategies for population suppression
Authors: Yue Han, Jackson Champer
Journal: Molecular Biology and Evolution (2025)

Genetic control strategies are promising solutions for control of pest populations and invasive species. Methods utilizing repeated releases of males such as Sterile Insect Technique (SIT), Release of Insects carrying a Dominant Lethal (RIDL), self-limiting gene drives, and gene disruptors are highly controllable methods, ensuring biosafety. Although models of these strategies have been built, detailed comparisons are lacking, particularly for some of the newer strategies. Here, we conducted a thorough comparative assessment of self-limiting genetic control strategies by individual-based simulation models. Specifically, we find that repeated releases greatly enhance suppression power of weak and self-limiting gene drives, enabling population elimination with even low efficiency and high fitness costs. Moreover, dominant female sterility further strengthens self-limiting systems that can either use gene drive or disruptors that target genes without a mechanism to bias their own inheritance. Some of these strategies are highly persistent, resulting in relatively low release ratios even when released males suffer high fitness costs. To quantitively evaluate different strategies independent from ecological impact, we proposed constant-population genetic load, which achieves over 95% accuracy in predicting simulation outcomes for most strategies, though it is not as precise in a few frequency-dependent systems. Our results suggest that many new self-limiting strategies are safe, flexible, and more cost-effective than traditional SIT and RIDL, and thus have great potential for population suppression of insects and other pests.
Haematological cancers and skin cancer: statistics from the Netherlands
Authors: Lena A von Schuckmann, Kiarash Khosrotehrani
Journal: British Journal of Dermatology (2025)

Journal Article Accepted manuscript Haematological cancers and skin cancer: statistics from the Netherlands Get access Lena A von Schuckmann, Lena A von Schuckmann Frazer Institute, Dermatology Research Centre, Experimental Dermatology Group, The University of Queensland, Brisbane, AustraliaDepartment of Dermatology, Princess Alexandra Hospital, Brisbane, Australia Search for other works by this author on: Oxford Academic Google Scholar Kiarash Khosrotehrani Kiarash Khosrotehrani Frazer Institute, Dermatology Research Centre, Experimental Dermatology Group, The University of Queensland, Brisbane, AustraliaDepartment of Dermatology, Princess Alexandra Hospital, Brisbane, Australia Correspondence: Kiarash Khosrotehrani Email:[email protected] Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljaf081, https://doi.org/10.1093/bjd/ljaf081 Published: 01 March 2025 Article history Received: 23 February 2025 Accepted: 24 February 2025 Published: 01 March 2025