tbuckley/cabot-search huggingface dataset:
Gelatin sponge patch grafting of microcryogel-based three-dimensional mesenchymal stem cells to alleviate acute liver failure
Authors: Haimeng Song, Xinyue Du, Yuanyuan Zhang, Wei Liu, Yi Luo, Yuxin Liu, Yongjia Xue, Mingyang Xu, Jizhen Lu, Wenwen Jia, Yanan Du, Lining Cao, Jianfeng Lu, Wencheng Zhang, Zhiying He
Journal: Biomaterials (2025)

The clinical application of human umbilical cord mesenchymal stem cells (hUCMSCs) in the treatment of liver failure faces challenges due to cell quality, short engraftment time, and limited efficacy. Here, gelatin microcryogel (GM) microcarriers with pore sizes ranging from 15 to 36 μm were tuned from mixed gelatin and glutaraldehyde to develop a 3D culture system of hUCMSCs with improved therapeutic effects. Bulk RNA sequencing and in vitro assays showed that 3D-hUCMSCs exhibited significant improvement in signaling pathways related to paracrine secretion and anti-inflammation. These 3D-hUCMSCs superior compared to 2D-hUCMSCs not only in terms of paracrine secretion, protection from oxidation, and resistance to mechanical force damage, but also had better liver function improvement effect than 2D-hUCMSCs when they were transplanted as single cells into liver injury mice. Furthermore, a gelatin sponge patch grafting (GSPG) strategy was developed to enable the direct engraftment of 3D-hUCMSCs within the GM microcarriers. The results showed that overall engraftment in the host liver was significantly improved, and the life span of transplanted hosts was extended. Our study provided a practical strategy to achieve high engraftment and long retraining time of 3D-hUCMSCs in rescuing acute liver failure with gelatin matrixes.
Clinical and Neurophysiological Effects of Robotically-Delivered fMRI-Guided Personalized Transcranial Magnetic Stimulation Therapy for Depression
Authors: Luke J. Hearne, Lachlan Webb, Robin Cash, Conor Robinson, Philip E. Mosley, Joanna Ng, Simon T. Thwaites, Simon Issa, Jessica Miller, Nga Yan Tse, Andrew Zalesky, Bjorn Burgher, Luca Cocchi
Journal: Psychotherapy and Psychosomatics (2025)

Introduction: Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an established treatment for refractory major depressive disorder (MDD), but treatment outcomes vary substantially from person to person. Recent evidence suggests that incorporating neuroimaging-based targeting may help improve clinical outcomes. Here, we report the initial clinical outcomes of our open-label fMRI-personalized treatment protocol from the Queensland Neurostimulation Centre (QNC). Methods: This open-label, nonrandomized study was conducted between November 2021 and September 2024. Participants were a referred sample aged between 19 and 84, meeting the criteria for treatment-resistant MDD (N=61). They received 20 or 30-weekday sessions of DLPFC rTMS. The stimulation site was personalized using each individual’s fMRI brain connectivity data. Results: The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS). MADRS was lower post-treatment (d=1.78, p&lt;.001), with 52% and 33% response and remission rates observed. Likewise, anxiety scores (Hamilton Anxiety Rating Scale) were lower post-treatment (d=1.27, p&lt;.001), with 46% and 28% response and remission rates observed. The treatment was most effective in patients who qualified for randomized controlled trials (RCTs; N=19, MADRS response=74%, remission=53%) and least effective in patients with bipolar or neurological disorders (N=8, MADRS response=37%, remission=25%). Neurophysiologically, functional brain connectivity in the personalized DLPFC-SGC pathway was less anti-correlated post-treatment (d=0.63, p&lt;.001). Conclusion: Our findings provide new clinical and neurophysiological evidence supporting the high effectiveness of fMRI-connectivity-guided personalized rTMS for MDD, especially in individuals without complex comorbidities. The results encourage future RCTs to assess the superiority of personalized targeting over standard TMS.
Dialectical Behaviour Therapy to Treat Emotion Dysregulation in Autistic adults without Intellectual Disability: A Randomised Controlled Trial
Authors: Doha Bemmouna, Emmett Rabot, Romain Coutelle, François Lefebvre, Sébastien Weibel, Luisa Weiner
Journal: Psychotherapy and Psychosomatics (2025)

Introduction: Emotion dysregulation is prevalent in autistic adults without intellectual disability whereby it has been associated with heightened non-suicidal self-injury and suicidal behaviours. Dialectical behaviour therapy (DBT) has shown to be feasible and preliminary findings suggest that it might reduce emotion dysregulation in this population. Yet studies evaluating the efficacy of DBT in this context are lacking. Methods: Sixty-three autistic adults presenting with emotion dysregulation as well as self-harm and/or suicidal behaviours were randomised either to the DBT condition (18-week treatment) or to the waiting list condition. Participants completed self-report scales, including emotion dysregulation, alexithymia, depression and quality of life, at 4 time points (pre-, mid-, post-therapy, six-month follow-up). Results: Emotion dysregulation improved in the DBT condition relative to the waiting list condition mid-therapy (β01 = -18.59 [-27.67 to -9.44], Pr (β01 &lt; 0) = 1.000), post- therapy (β02 = -31.91 [-41.67 to -22.30], Pr (β02 &lt; 0) = 1.000), with lasting improvements at follow-up. Alexithymia improvement mediated the therapy effects on emotion dysregulation. Moreover, depressive symptoms and quality of life improved in the DBT condition relative to the waiting list condition post-therapy, with improvements lasting at follow-up. Conclusion: DBT was found to be effective to reduce emotion dysregulation in autistic adults presenting with self-harm and/or suicidal behaviour. Additionally, improvements on depression and quality-of-life were observed post-therapy. Interestingly, the improvements on emotion dysregulation were mediated by a decrease in alexithymia, consistent with research showing that alexithymia is a central mechanism of emotion dysregulation in autistic adults.
A Million Years of Mammoth Mitogenome Evolution
Authors: J Camilo Chacón-Duque, Jessica A Thomas Thorpe, Wenxi Li, Marianne Dehasque, Patricia Pečnerová, Axel Barlow, David Díez-del-Molino, Kirstin Henneberger, Chenyu Jin, Kelsey N Moreland, Johanna L A Paijmans, Tom van der Valk, Michael V Westbury, Flore Wijnands, Ian Barnes, Mietje Germonpré, Elizabeth Hall, Susan Hewitson, Dick Mol, Pavel Nikolskiy, Mikhail Sablin, Sergey Vartanyan, Grant D Zazula, Anders Götherström, Adrian M Lister, Michael Hofreiter, Peter D Heintzman, Love Dalén
Journal: Molecular Biology and Evolution (2025)

Abstract The genomic study of specimens dating to the Early and Middle Pleistocene (EP and MP), a period spanning from 2.6 million years ago (Ma) to 126 thousand years ago (ka), has the potential to elucidate the evolutionary processes that shaped present-day biodiversity. Obtaining genomic data from this period is challenging, but mitochondrial DNA, given its higher abundance compared to nuclear DNA, could play an important role to understand evolutionary processes at this time scale. In this study, we report 34 new mitogenomes, including two EP and nine MP mammoth (Mammuthus spp.) specimens from Siberia and North America and analyze them jointly with &amp;gt;200 publicly available mitogenomes to reconstruct a transect of mammoth mitogenome diversity throughout the last million years. We find that our EP mitogenomes fall outside the diversity of all Late Pleistocene (LP) mammoths, while those derived from MP mammoths are basal to LP mammoth Clades 2 and 3, supporting an ancient Siberian origin of these lineages. In contrast, the geographical origin of Clade 1 remains unresolved. With these new deep-time mitogenomes, we observe diversification events across all clades that appear consistent with previously hypothesized MP and LP demographic changes. Furthermore, we improve upon an existing methodology for molecular clock dating of specimens &amp;gt;50 ka, demonstrating that specimens need to be individually dated to avoid biases in their age estimates. Both the molecular and analytical improvements presented here highlight the importance of deep-time genomic data to discover long-lost genetic diversity, enabling better assessments of evolutionary histories.
Single-cell and spatial transcriptomic analyses revealing tumor microenvironment remodeling after neoadjuvant chemoimmunotherapy in non-small cell lung cancer
Authors: Xiaolu Cui, Siyuan Liu, He Song, Jingjing Xu, Yanbin Sun
Journal: Molecular Cancer (2025)

Non-small cell lung cancer (NSCLC) represents the most common pathological type of lung cancer, and the combination of neoadjuvant immunotherapy with chemotherapy has emerged as the first-line treatment for NSCLC. Nevertheless, the efficacy of this therapeutic approach remains variable. The present study aims to examine the impact of chemoimmunotherapy in NSCLC patients, with a view to identifying key molecules, critical cell subpopulations, communication patterns and spatial distributions that potentially correlate with therapeutic sensitivity. A total of 16 lung cancer tissue samples were collected from a cohort of 12 NSCLC patients and subjected to single-cell RNA and spatial transcriptome sequencing. Our data demonstrated that the distribution of CD4 + Treg T cells and mCAFs indicated an immunosuppressive tumor microenvironment, while the accumulation of CD4 + Th17 T cells and iCAFs could act as a positive marker for the sensitivity to chemoimmunotherapy. Furthermore, a significant high level of SELENOP-macrophages was observed in tissues from positive responders, and a strong co-localization between SELENOP-macrophages and antigen-presenting cancer associated fibroblasts (CAFs) in the tumor boundaries was identified, indicating the cooperative roles of these two cell types in response to combined therapy. Moreover, SELENOP-macrophages were observed to be accumulated in tertiary lymphoid structures, which further suggested its critical role in recruiting lymphocytes. Furthermore, analysis of cell-cell communication, based on spatial transcriptomics, suggests that the interactions between SELENOP-macrophages, apCAFs, CD4 + and CD8 + T cells were significantly enhanced in responders. In addition, SELENOP-macrophages recruited CD4 + Naïve, Helper and CD8 + Naïve T cells through pathways such as the cholesterol, interleukin, chemokine and HLA when responding to combined therapy. The present study further unveils the dynamic spatial and transcriptional changes in the tumor microenvironment of non-small cell lung cancer in response to combination therapy.
Multimodal sequencing of neoadjuvant nivolumab treatment in hepatocellular carcinoma reveals cellular and molecular immune landscape for drug response
Authors: Fanhong Zeng, Qingyang Zhang, Yu-Man Tsui, Huanhuan Ma, Lu Tian, Abdullah Husain, Jingyi Lu, Joyce Man-Fong Lee, Vanilla Xin Zhang, Po-Man Li, Gary Cheuk-Hang Cheung, Tan-To Cheung, Daniel Wai-Hung Ho, Irene Oi-Lin Ng
Journal: Molecular Cancer (2025)

A striking characteristic of liver cancer is its extensive heterogeneity, particularly with regard to its varied response to immunotherapy. In this study, we employed multimodal sequencing approaches to explore the various aspects of neoadjuvant nivolumab treatment in liver cancer patients. We used spatially-resolved transcriptomics, single- and bulk-cell transcriptomics, and TCR clonotype analyses to examine the spatiotemporal dynamics of the effects of nivolumab. We observed a significantly higher clonal expansion of T cells in the tumors of patients who responded to the treatment, while lipid accumulation was detected in those of non-responders, likely due to inherent differences in lipid metabolic processes. Furthermore, we found a preferential enrichment of T cells, which was associated with a better drug response. Our results also indicate a functional antagonism between tumor-associated macrophages (TAMs) and CD8 cells and their spatial separation. Notably, we identified a UBASH3B/NR1I2/CEACAM1/HAVCR2 signaling axis, highlighting the intense communication among TAMs, tumor cells, and T-cells that leads to pro-tumorigenic outcomes resulting in poorer nivolumab response. In summary, using integrative multimodal sequencing investigations, combined with the multi-faceted exploration of pre- and post-treatment samples of neoadjuvant nivolumab-treated HCC patients, we identified useful mechanistic determinants of therapeutic response. We also reconstructed the spatiotemporal model that recapitulates the physiological restoration of T cell cytotoxicity by anti-PD1 blockade. Our findings could provide important biomarkers and explain the mechanistic basis differentiating the responders and non-responders.
Orofacial granulomatosis secondary to sodium metabisulfite contact allergy
Authors: Vanessa Tran, Celestine Wong, Simone Belobrov, Ryan De Cruz, Vanessa Morgan, Laura Scardamaglia
Journal: British Journal of Dermatology (2025)

Dietary triggers are well-recognised contributors to orofacial granulomatosis. As such, a cinnamon- and benzoate-free diet is often suggested as first-line management. We report a novel case of orofacial granulomatosis secondary to sodium metabisulfite, which was identified through patch testing.
The response to anti–PD-1 and anti–LAG-3 checkpoint blockade is associated with regulatory T cell reprogramming
Authors: Annah S. Rolig, Xiyu Peng, Elizabeth R. Sturgill, Nisha Holay, Melissa Kasiewicz, Courtney Mick, Grace Helen Mcgee, William Miller, Yoshinobu Koguchi, Johanna Kaufmann, Niranjan Yanamandra, Sue Griffin, James Smothers, Matthew Adamow, Jasme Lee, Ronglai Shen, Margaret K. Callahan, William L. Redmond
Journal: Science Translational Medicine (2025)

Immune checkpoint blockade (ICB) has revolutionized cancer treatment; however, many patients develop therapeutic resistance. We previously identified and validated a pretreatment peripheral blood biomarker, characterized by a high frequency of LAG-3 + lymphocytes, that predicts resistance in patients receiving anti–PD-1 (aPD-1) ICB. To better understand the mechanism of aPD-1 resistance, we identified murine tumor models with a high LAG-3 + lymphocyte frequency (LAG-3 hi ), which were resistant to aPD-1 therapy, and LAG-3 lo murine tumor models that were aPD-1 sensitive, recapitulating the predictive biomarker we previously described in patients. LAG-3 hi tumor-bearing mice were sensitive to aPD-1 + anti–LAG-3 (aLAG-3) therapy, and this benefit was CD8 + T cell dependent. The efficacy of combination therapy was enhanced in LAG-3 hi (but not LAG-3 lo ) mice with depletion of CD4 + T cells. Furthermore, responses to aPD-1 + aLAG-3 correlated with regulatory T cell (T reg ) phenotypic plasticity in LAG-3 hi mice, suggesting a specific role for T regs in response to aPD-1 + aLAG-3 treatment. Using T reg fate–tracking Foxp3 GFP-Cre-ERT2 × ROSA YFP reporter mice, we demonstrated that expanded populations of unstable T regs correlated with improved response to combination therapy in LAG-3 hi mice. Complementing these preclinical data, an increased proportion of unstable T regs also correlated with higher response rate and improved survival after aPD-1 + aLAG-3 therapy in a cohort of patients with metastatic melanoma ( n = 117). These data indicate that T reg phenotypic plasticity affects aPD-1 + aLAG-3 responsiveness, which may represent a biomarker to aid patient selection and a rational therapeutic target for a subset of PD-1–refractory patients.
Spatial genomics: Mapping the landscape of fibrosis
Authors: Prasad Palani Velu, Roxanna E. Abhari, Neil C. Henderson
Journal: Science Translational Medicine (2025)

Organ fibrosis causes major morbidity and mortality worldwide. Treatments for fibrosis are limited, with organ transplantation being the only cure. Here, we review how various state-of-the-art spatial genomics approaches are being deployed to interrogate fibrosis across multiple organs, providing exciting insights into fibrotic disease pathogenesis. These include the detailed topographical annotation of pathogenic cell populations and states, detection of transcriptomic perturbations in morphologically normal tissue, characterization of fibrotic and homeostatic niches and their cellular constituents, and in situ interrogation of ligand-receptor interactions within these microenvironments. Together, these powerful readouts enable detailed analysis of fibrosis evolution across time and space.
The mRNA export pathway licenses viral mimicry response and antitumor immunity by actively exporting nuclear retroelement transcripts
Authors: Xiaoqiang Wang, Jiaxing Jin, Han Yan, Jinhua Liu, Shan Huang, Hui Bai, Mingrui Guo, Xinyue Cheng, Ting Deng, Yi Ba, Yong Gu, Xin Gao, Deqing Hu
Journal: Science Translational Medicine (2025)

Nuclear retroelement transcripts (RTs), which can be elicited both transcriptionally and posttranscriptionally, form double-stranded RNA (dsRNA) in cytosol to trigger the viral mimicry response (VMR) and antitumor immunity. However, the strength of the induced VMR varies tremendously across tumor types, and the underlying mechanisms remain poorly understood. Here, we demonstrate that the mRNA export pathway modulates the VMR through actively exporting nuclear RTs for cytosolic dsRNA formation after their induction. Tumor cells hijack this process for immune evasion through aberrant coactivator-associated arginine methyltransferase 1 (CARM1) expression. Mechanistically, we show that the cytoplasmic transportation of RTs by the mRNA export pathway is counteracted by the RNA exosome, which cleaves multiple transcripts within this pathway, including those encoding the essential DExD-box helicase 39A (DDX39A) and the adaptor protein ALYREF. CARM1 enhances the RNA exosome activity to attenuate the nuclear export of RTs by the mRNA export pathway through two synergistic mechanisms: (i) transcriptionally activating several RNA exosome components and (ii) posttranslationally methylating arginine 6 of the RNA exosome subunit EXOSC1, which protects it from proteasome-mediated degradation. Collectively, our study highlights the critical active regulatory role of the mRNA export pathway in transporting nuclear RTs into the cytosol for triggering the VMR and tumor immunity. Furthermore, we propose that enhancing the mRNA export pathway activity, either through CARM1 inhibition or RNA exosome modulation, could reinforce the therapeutic agent-induced VMR, thus holding the promise for overcoming tumor immune evasion and immunotherapy resistance.
Rapid tuberculosis diagnosis from respiratory or blood samples by a low cost, portable lab-in-tube assay
Authors: Brady M. Youngquist, Julian Saliba, Yelim Kim, Thomas J. Cutro, Christopher J. Lyon, Juan Olivo, Ngan Ha, Janelle Fine, Rebecca Colman, Carlos Vergara, James Robinson, Sylvia LaCourse, Richard S. Garfein, Donald G. Catanzaro, Christoph Lange, Eddy Perez-Then, Edward A. Graviss, Charles D. Mitchell, Timothy Rodwell, Bo Ning, Tony Y. Hu
Journal: Science Translational Medicine (2025)

Rapid portable assays are needed to improve diagnosis, treatment, and reduce transmission of tuberculosis (TB), but current tests are not suitable for patients in resource-limited settings with high TB burden. Here we report a low complexity, lab-in-tube system that is read by an integrated handheld device that detects Mycobacterium tuberculosis ( Mtb ) DNA in blood and respiratory samples from a variety of clinical settings. This microprocessor-controlled device uses an LCD user interface to control assay performance, automate assay analysis, and provide results in a simple readout. This point-of-care single-tube assay uses a DNA enrichment membrane and a low-cost cellulose disc containing lyophilized recombinase polymerase amplification and CRISPR-Cas12a reagents to attain single-nucleotide specificity and high sensitivity within 1 hour of sample application, without a conventional DNA isolation procedure. Assay results obtained with serum cell–free DNA isolated from a cohort of children aged 1 to 16 years detected pulmonary and extrapulmonary TB with high sensitivity versus culture and GeneXpert MTB/RIF results (81% versus 55% and 68%) and good specificity (94%), meeting the World Health Organization target product profile criteria for new nonsputum TB diagnostics. Changes in assay results for serum isolated during treatment were also highly predictive of clinical response. Results obtained with noninvasive sputum and saliva specimens from adults with bacteriologically confirmed pulmonary TB were also comparable to those reported for reference methods. This rapid and inexpensive lab-in-tube assay approach thus represents one means to address the need for point-of-care TB diagnostics useable in low-resource settings.
Collagen V regulates renal function after kidney injury and can be pharmacologically targeted to enhance kidney repair in mice
Authors: Lianjiu Su, Qihao Sun, Yusheng Li, Juan Felipe Alvarez, Bo Tao, Guanglin Zhang, Yiqian Gu, Mark R. Hanudel, Alejandro Espinoza, Linlin Zhang, Calvin Pan, James R. Hilser, Jaana A. Hartiala, Shen Li, Matteo Pellegrini, Hooman Allayee, Aldons J. Lusis, Arjun Deb
Journal: Science Translational Medicine (2025)

Kidney fibrosis determines clinical outcomes in individuals with chronic kidney disease (CKD). The stoichiometric ratio of collagens in renal scar differs from that of healthy kidney extracellular matrix (ECM), but the functional importance of altered collagen types in injured kidneys remains unclear. Using human population studies, we show that circulating protein and renal mRNA amounts of collagen V A1 (COL5A1) exhibited associations with kidney disease and incident CKD risk. We show that Col5a1 regulates the degree of postinjury fibrosis and renal function. Mice with conditionally knocked out Col5a1 ( Col5a1 CKO) exhibited decreased renal function and greater renal fibrosis after dietary adenine- or ureteric obstruction–mediated kidney injury. Renal fibroblasts in Col5a1 CKO animals up-regulated the profibrotic αvβ3 integrin. Inhibition of αvβ3 signaling with a small molecule, cilengitide, rescued postinjury renal function in Col5a1 CKO animals. Using the hybrid mouse diversity panel that comprises 100 diverse inbred strains of mice, we observed that gene expression of Col5a1 after injury exhibited genetic variation across 100 strains. Strains with low Col5a1 expression after injury exhibited worse renal function compared with animals that had higher degrees of expression. We next measured Col5a1 expression in peripheral blood mononuclear cells in mice to identify nonresponder strains that did not have increased Col5a1 expression after kidney injury. We observed that administration of cilengitide in nonresponder strains significantly rescued postinjury renal fibrosis and function. These studies point to the feasibility of precision medicine approaches to target Col5a1 for enhancing renal repair.