tbuckley/cabot-search huggingface dataset:
Neutrophils in Tissue Injury and Repair: Molecular Mechanisms and Therapeutic Targets
Authors: Luying Yang, Fan Shi, Feng Cao, Le Wang, Jianzhen She, Boling He, Xiaoying Xu, Liang Kong, Bolei Cai
Journal: MedComm (2025)

ABSTRACT Tissue repair represents a highly intricate and ordered dynamic process, critically reliant on the orchestration of immune cells. Among these, neutrophils, the most abundant leukocytes in the body, emerge as the initial immune responders at injury sites. Traditionally recognized for their antimicrobial functions in innate immunity, neutrophils now garner attention for their indispensable roles in tissue repair. This review delves into their novel functions during the early stages of tissue injury. We elucidate the mechanisms underlying neutrophil recruitment and activation following tissue damage and explore their contributions to vascular network formation. Furthermore, we investigate the pivotal role of neutrophils during the initial phase of repair across different tissue types. Of particular interest is the investigation into how the fate of neutrophils influences overall tissue healing outcomes. By shedding light on these emerging aspects of neutrophil function in tissue repair, this review aims to pave the way for novel strategies and approaches in future organ defect repair, regeneration studies, and advancements in tissue engineering. The insights provided here have the potential to significantly impact the field of tissue repair and regeneration.
Strategically Designed Mitochondria‐Targeting AIEgens for Effective Eradication of Primary and Metastatic Tumors via Synergistic Phototherapy and Induced Immunogenic Cell Death
Authors: Lin Yang, Jiachang Huang, Yanan Liao, Deping Hu, Yake He, Na Feng, Ryan T. K. Kwok, Jacky W. Y. Lam, Jing Zhang, Benzhao He, Ben Zhong Tang
Journal: Advanced Healthcare Materials (2025)

Abstract In recent years, photoimmunotherapy has emerged as an innovative modality in antitumor therapy, garnering significant research interest due to its integration of the advantages of both phototherapy and immunotherapy. However, despite extensive efforts to advance photoimmunotherapy, the design strategies for photoimmunotherapy agents remain uncertain, significantly hindering progress in this field. Here, a novel molecular design strategy for developing superb photoimmunotherapy agents that integrates aggregation‐induced emission (AIE) activity, mitochondria targeting, high‐efficiency reactive oxygen species generation, and high photothermal conversion capabilities into a single molecule is proposed. A comprehensive study demonstrates that the target molecule (TPETTBI) that is strategically designed can exert prominent photodynamic therapy (PDT) and photothermal therapy (PTT) effects, leading to tumor cell death. More importantly, the synergistic action of PDT and PTT can further induce mitochondrial dysfunction and trigger large‐scale immunogenic cell death (ICD) to attain a long‐lasting effect of antitumor immunity. Therefore, this work provides new insights into the rational design of phototherapy agents for precise and efficient tumor treatment by integrating synergistic PDT, PTT, and ICD‐based immunotherapy within a single molecule.
Author Correction: Transforming healthcare through just, equitable and quality driven artificial intelligence solutions in South Asia
Authors: Sushmita Adhikari, Iftikhar Ahmed, Deepak Bajracharya, Bishesh Khanal, Chandrasegarar Solomon, Kapila Jayaratne, Khondaker Abdullah Al Mamum, Muhammad Shamim Hayder Talukder, Sunila Shakya, Suresh Manandhar, Zahid Ali Memon, Moinul Haque Chowdhury, Ihtesham Ul Islam, Noor Sabah Rakhshani, M Imran Khan
Journal: npj Digital Medicine (2025)
In desmosomes direct inhibition precedes p38MAPK-mediated uncoupling to reduce Dsg3 adhesion by pemphigus autoantibodies
Authors: Michael Fuchs, Miriam Möchel, Mariya Y Radeva, Thomas Schmitt, Amir S Yazdi, Takashi Hashimoto, Jens Waschke
Journal: British Journal of Dermatology (2025)

Abstract Background Pemphigus vulgaris (PV) is an autoimmune blistering skin disease caused by impaired desmosome adhesion. Altered signaling pathways and direct inhibition of desmoglein (Dsg) binding contribute to loss of cell adhesion but the sequence of these events is still matter of debate. Objectives Characterization of the early sequence of events after autoantibody binding to Dsg3 in pemphigus pathogenesis. Methods STED, STED/AFM-SMFS, Triton X-100 fractionation assay, Western blotting, immunofluorescence staining, keratinocyte dissociation assays. Results We identify that in human keratinocytes the primary loss of cell adhesion and Dsg3 binding occurs as soon as autoantibodies are detectable in desmosomes which is as early as after 5 min for the monoclonal anti-Dsg3 antibody AK23 and 15 min after addition of PV-IgG from patients. Activation of p38MAPK, which is a central signaling mechanism in pemphigus, was significant after 30 min but not detectable in desmosomes after 5 min of AK23 incubation. Nevertheless, p38MAPK was required for loss of cytoskeletal anchorage of Dsg3 molecules in desmosomes and inhibition of p38MAPK blunted loss of Dsg3 binding and cell adhesion. Conclusions These results demonstrate that autoantibody-induced direct inhibition of Dsg3 binding preceded p38MAPK-mediated cytoskeletal uncoupling at desmosomes. Thus, the signaling function of Dsg3 to activate p38MAPK is triggered by loss of trans-interaction, which is the primary target point for therapeutic strategies to stabilize keratinocyte adhesion in pemphigus.
Immunogenicity of MVA-BN vaccine deployed as mpox prophylaxis: a prospective, single-centre, cohort study and analysis of transcriptomic predictors of response
Authors: Philip G Drennan, Nicholas M Provine, Stephanie A Harris, Ashley Otter, Kate Hollett, Cushla Cooper, Roel P H De Maeyer, Beatrice Nassanga, Alberta Ateere, Maria Fransiska Pudjohartono, Yanchun Peng, Ji-Li Chen, Scott Jones, Nurul Huda Mohamad Fadzillah, Alba Grifoni, Allessandro Sette, Iman Satti, Sam M Murray, Cathy Rowe, Sema Mandal, Bassam Hallis, Paul Klenerman, Tao Dong, Duncan Richards, James Fullerton, Helen McShane, Mark Coles
Journal: The Lancet Microbe (2025)
Intrinsic properties of the lymph node render it immunologically susceptible to metastasis
Authors: Benjamin M. Kahn, Raymond W.S. Ng, Il-Kyu Kim, Cody Eskandarian, Chelsey O. Chen, Bing Huang, Alfredo Lucas, Lequn Li, Ivan Maillard, Ben Z. Stanger
Journal: Cancer Discovery (2025)

Abstract Lymph nodes (LNs) are the staging grounds for anti-tumor immunity, therefore their high susceptibility to metastatic colonization is a paradox. Previous studies have suggested that extrinsic tumor-derived factors precondition the draining LN to enable tumor cell survival by promoting a state of immune suppression. Here, we investigate whether properties of the LN itself may impede its ability to clear metastasizing tumor cells. Using multiple immunocompetent transplant models, we show that LNs possess intrinsic features, independent of preconditioning, which make them an advantageous site for tumor cells to evade T cell control. Tumor growth in the LN is facilitated by regulatory T cells, which locally suppress the cytolytic capacity of tumor-specific CD8 T cells by restricting IL-2. These findings identify an intrinsic mechanism that contributes to the high rate of LN metastasis in solid tumors.
Pan-genomic analysis highlights genes associated with agronomic traits and enhances genomics-assisted breeding in alfalfa
Authors: Fei He, Shuai Chen, Yangyang Zhang, Kun Chai, Qing Zhang, Weilong Kong, Shenyang Qu, Lin Chen, Fan Zhang, Mingna Li, Xue Wang, Huigang Lv, Tiejun Zhang, Xiaofan He, Xiao Li, Yajing Li, Xianyang Li, Xueqian Jiang, Ming Xu, Bilig Sod, Junmei Kang, Xingtan Zhang, Ruicai Long, Qingchuan Yang
Journal: Nature Genetics (2025)
Cognitive behavioral therapy skills via a smartphone app for subthreshold depression among adults in the community: the RESiLIENT randomized controlled trial
Authors: Toshi A Furukawa, Aran Tajika, Rie Toyomoto, Masatsugu Sakata, Yan Luo, Masaru Horikoshi, Tatsuo Akechi, Norito Kawakami, Takeo Nakayama, Naoki Kondo, Shingo Fukuma, Ronald C Kessler, Helen Christensen, Alexis Whitton, Inbal Nahum-Shani, Wolfgang Lutz, Pim Cuijpers, James M S Wason, Hisashi Noma
Journal: Nature Medicine (2025)

Subthreshold depression, defined as a depressive status falling short of the diagnostic threshold for major depression, is common, disabling and constitutes a risk factor for future depressive episodes. Cognitive behavioral therapies (CBT) have been shown to be effective but are usually provided as packages of various skills. Little research has been done to investigate whether all their components are beneficial and contributory to mental health promotion. We addressed this issue by developing a smartphone CBT app that implements five representative CBT skills (behavioral activation, cognitive restructuring, problem solving, assertion training and behavior therapy for insomnia), and conducting a master randomized study that included four 2 × 2 factorial trials to enable precise estimation of skill-specific efficacies. Between September 2022 and February 2024, we recruited 3,936 adult participants with subthreshold depression. Among those randomized, the follow-up rate was 97% at week 6 and adherence to the app was 84%. The study showed that all included CBT skills and their combinations differentially beat all three control conditions of delayed treatment, health information or self-check, with effect sizes ranging between -0.67 (95% confidence interval: -0.81 to -0.53) and -0.16 (-0.30 to -0.02) for changes in depressive symptom severity from baseline to week 6, as measured with the Patient Health Questionnaire-9 scores. Knowledge of the active ingredients of CBT can better inform the design of more effective and scalable psychotherapies in the future. (UMIN Clinical Trials Registry UMIN000047124 ).
CMV serostatus is associated with improved survival and delayed toxicity onset following anti-PD-1 checkpoint blockade
Authors: Gusztav Milotay, Martin Little, Robert A Watson, Dylan Muldoon, Sophie MacKay, Ayako Kurioka, Orion Tong, Chelsea A Taylor, Isar Nassiri, Louisa M Webb, Oluwafemi Akin-Adigun, Julia Bremke, Weiyu Ye, Bo Sun, Piyush Kumar Sharma, Ros Cooper, Sara Danielli, Flavia Matos Santo, Alba Verge de Los Aires, Guangyi Niu, Lea Cohen, Esther Ng, James J Gilchrist, Amanda Y Chong, Alex Mentzer, Victoria Woodcock, Nicholas Coupe, Miranda J Payne, Michael Youdell, Mark R Middleton, Paul Klenerman, Benjamin P Fairfax
Journal: Nature Medicine (2025)

Abstract Cytomegalovirus (CMV) is a globally endemic latent herpes virus that profoundly impacts T cell immunity. We investigated the oncological consequences of CMV infection across 341 prospectively recruited patients receiving immune checkpoint blockade (ICB) for melanoma. CMV + patients with metastatic melanoma (MM) have higher lymphocyte counts, reduced neutrophil to lymphocyte ratio and divergent CD8 + T cell gene expression. Combination anti-CTLA-4/anti-PD-1 ICB, but not single-agent anti-PD-1 ICB, induces cytotoxicity and CMV-associated gene expression in CD8 + T cells from CMV − patients. Correspondingly, overall survival was independent of CMV serostatus in combination anti-CTLA-4/anti-PD-1 ICB recipients (CMV + hazard ratio for death: 1.02, P = 0.92), whereas CMV + single-agent anti-PD-1 ICB recipients had improved overall survival (CMV + hazard ratio for death: 0.37, P &lt; 0.01), a finding also seen in CMV + adjuvant single-agent anti-PD-1 ICB recipients (CMV + hazard ratio for recurrence: 0.19, P = 0.03). We identify TBX21 , encoding T-bet, as a transcriptional driver of CMV-associated CD8 + T cell gene expression, finding that TBX21 expression is predictive of overall survival (hazard ratio: 0.62, P = 0.026). CMV + patients unexpectedly show reduced cumulative incidence of grade 3+ immune-related adverse events at 6 months (0.30 versus 0.52, P = 2.2 × 10 −5 ), with lower incidence of colitis ( P = 7.8 × 10 −4 ) and pneumonitis ( P = 0.028), an effect replicated in non-melanoma ICB recipients ( n = 58, P = 0.044). Finally, we find reduced CMV seropositivity rates in patients with MM compared with UK Biobank controls (odds ratio: 0.52, P = 1.8 × 10 −4 ), indicating CMV seropositivity may protect against MM. Specifically, patients with BRAF -mutated MM are less likely to be CMV + (odds ratio = 2.2, P = 0.0054), while CMV − patients present 9 yr earlier with BRAF wild-type MM ( P = 1.3 × 10 −4 ). This work reveals an interaction between CMV infection, MM development according to BRAF status and response to ICB, while demonstrating CMV infection is protective against severe ICB immune-related adverse events, highlighting the potential importance of previous infection history and chronic immune activation in MM development and immunotherapy outcomes.
Increased TMEM106B levels lead to lysosomal dysfunction which affects synaptic signaling and neuronal health
Authors: Jolien Perneel, Miranda Lastra Osua, Sara Alidadiani, Nele Peeters, Linus De Witte, Bavo Heeman, Simona Manzella, Riet De Rycke, Mieu Brooks, Ralph B Perkerson, Elke Calus, Wouter De Coster, Manuela Neumann, Ian R A Mackenzie, Debby Van Dam, Bob Asselbergh, Tommas Ellender, Xiaolai Zhou, Rosa Rademakers
Journal: Molecular Neurodegeneration (2025)

Abstract Background Genetic variation in Transmembrane protein 106B (TMEM106B) is known to influence the risk and presentation in several neurodegenerative diseases and modifies healthy aging. While evidence from human studies suggests that the risk allele is associated with higher levels of TMEM106B, the contribution of elevated levels of TMEM106B to neurodegeneration and aging has not been assessed and it remains unclear how TMEM106B modulates disease risk. Methods To study the effect of increased TMEM106B levels, we generated Cre-inducible transgenic mice expressing human wild-type TMEM106B. We evaluated lysosomal and neuronal health using in vitro and in vivo assays including transmission electron microscopy, immunostainings, behavioral testing, electrophysiology, and bulk RNA sequencing. Results We created the first transgenic mouse model that successfully overexpresses TMEM106B, with a 4- to 8-fold increase in TMEM106B protein levels in heterozygous (hTMEM106B(+)) and homozygous (hTMEM106B(++)) animals, respectively. We showed that the increase in TMEM106B protein levels induced lysosomal dysfunction and age-related downregulation of genes associated with neuronal plasticity, learning, and memory. Increased TMEM106B levels led to altered synaptic signaling in 12-month-old animals which further exhibited an anxiety-like phenotype. Finally, we observed mild neuronal loss in the hippocampus of 21-month-old animals. Conclusion Characterization of the first transgenic mouse model that overexpresses TMEM106B suggests that higher levels of TMEM106B negatively impacts brain health by modifying brain aging and impairing the resilience of the brain to the pathomechanisms of neurodegenerative disorders. This novel model will be a valuable tool to study the involvement and contribution of increased TMEM106B levels to aging and will be essential to study the many age-related diseases in which TMEM106B was genetically shown to be a disease- and risk-modifier. Graphical Abstract
Systemic Inflammation and Anhedonic Responses to an Inflammatory Challenge in Adults With Major Depressive Disorder: A Randomized Controlled Trial
Authors: Jonathan Savitz, Leandra K. Figueroa-Hall, T. Kent Teague, Hung-Wen Yeh, Haixia Zheng, Rayus Kuplicki, Kaiping Burrows, Nour El-Sabbagh, MacGregor Thomas, Isaac Ewers, Yoon-Hee Cha, Salvador Guinjoan, Sahib S. Khalsa, Martin P. Paulus, Michael R. Irwin
Journal: American Journal of Psychiatry (2025)

The authors sought to determine whether an inflammatory challenge with lipopolysaccharide (LPS) differentially impacts symptoms of anhedonia in participants with major depressive disorder with high (≥3 mg/L) and low (≤1.5 mg/L) serum C-reactive protein (CRP) concentrations. Sixty-eight participants with major depressive disorder were randomly assigned, in a 1:1 ratio, to receive LPS (0.8 ng/kg body weight) or placebo (saline) in a parallel-group double-blind design. Participants were stratified according to baseline CRP concentrations, yielding four groups: high-CRP LPS (N=13), low-CRP LPS (N=19), high-CRP placebo (N=13), and low-CRP placebo (N=19). Blood was sampled at baseline, at 1, 1.5, 3.5, 6, and 24 hours, and 1 week after LPS or saline administration, with concurrent assessment of psychological outcomes. The primary outcome measure was the Snaith-Hamilton Pleasure Scale (SHAPS), and the primary contrast of interest was the change between baseline and 1.5 hours (peak of the inflammatory response) in the high-CRP versus low-CRP groups receiving LPS. Secondary outcomes included the Montgomery-Åsberg Depression Rating Scale (MADRS) and serum levels of three cytokines: interleukin-6 (IL-6), IL-10, and tumor necrosis factor (TNF). Data were analyzed with linear mixed models. Significantly greater increases in self-reported anhedonia (on the SHAPS) and IL-6 levels were observed between baseline and 1.5 hours in the high-CRP versus low-CRP LPS groups. There were no significant differences for TNF and IL-10. The MADRS was not administered at 1.5 hours; secondary analyses showed a significant group-by-condition-by-time interaction driven by a greater decrease in MADRS scores between baseline and 24 hours in the high-CRP group. Depressed individuals with systemic inflammation appeared to be biologically primed to respond more strongly to inflammatory stimuli, and psychologically, this sensitization impacted the symptom of anhedonia, the primary outcome.
Drug Delivery Platform Targeting MMP9 in Combination with Photothermal Therapy to Improve Tumor Chemosensitivity
Authors: Jixian Fu, Chunyu Song, Shan Jiang, Shuping Yang, Qianjiang Wu, Xiaolong Liu, Zhiwen Hong, Rouhan A, Bolong Li, Guofan Qu, Tengchuang Ma, Haibo Shao
Journal: Advanced Healthcare Materials (2025)

Abstract Tumor chemotherapy insensitivity poses a significant challenge in cancer treatment, with angiogenesis being a key contributing factor. Angiogenesis supplies oxygen and nutrients to tumor cells, thereby impairing treatment outcomes. Based on these findings, an MMP9‐responsive carbon quantum dot‐based nanoplatform (MMP9i@MTX@CQDs) encapsulating methotrexate (MTX) and an MMP9 inhibitor (MMP9i) is developed to overcome chemotherapy insensitivity. Targeting the high expression of MMP9 in tumors, the platform releases its payload in a responsive manner. Under near‐infrared (NIR) irradiation, the system effectively downregulated angiogenesis‐related molecules, including VEGF and CD31, and inhibited the Wnt/β‐catenin signaling pathway, thereby reversing chemotherapy insensitivity. This nanoplatform integrates MMP9‐responsive CQDs with MTX, enabling photothermal therapy (PTT) and MMP9 inhibition, offering a robust and safe strategy to sensitize tumors to chemotherapy.
Establishing measurable residual disease trajectories for patients on treatment for newly diagnosed multiple myeloma as benchmark for deployment of T-cell redirection therapy
Authors: Susan Bal, Tylan Magnusson, Gayathri Ravi, Smith Giri, Kelly Godby, Binod Dhakal, Natalie S Callander, Rebecca W Silbermann, Bhagirathbhai Dholaria, Vishnu B Reddy, Luciano J Costa
Journal: Blood Cancer Journal (2025)

Autologous stem cell transplantation (ASCT) has been the prime consolidative strategy to increase the depth and duration of response in newly diagnosed multiple myeloma (NDMM), albeit with short- and long-term toxicities. Minimal residual disease (MRD) is an important early response endpoint correlating with clinically meaningful outcomes and may be used to isolate the effect of ASCT. We report the impact of ASCT on MRD burden and generate a benchmark for evaluation of novel treatments as consolidation. We collected MRD by next generation sequencing (NGS; clonoSEQ®) post induction and post-ASCT in consecutive patients (N = 330, quadruplet, N = 279; triplet, N = 51). For patients receiving quadruplets, MRD < 10-5 post-induction was 29% (MRD < 10-6 15%) increasing to 59% post-ASCT (MRD < 10-6 45%). Among patients with MRD > 10-5 post-induction, ASCT lowered the MRD burden>1 log10 for 69% patients. The use of quadruplet induction (vs. triplet) did not reduce the effect of ASCT on MRD burden. Reduction in MRD burden with ASCT was most pronounced in patients with high-risk chromosome abnormalities.This dataset provides granular data to delineate the impact of ASCT on MRD as legacy consolidative strategy in NDMM and provides an important benchmark for evaluation of efficacy of TCRT as experimental consolidative strategy.
Age‐related penetrance of phospholamban p.Arg14del cardiomyopathy
Authors: Tom E. Verstraelen, Freyja H.M. van Lint, Remco de Brouwer, Virginnio M. Proost, Esmee van Drie, Laurens P. Bosman, Lotte Weverink, Karim Taha, Thais Bueren, Aeilko H. Zwinderman, Cathelijne Dickhoff, Toon Oomen, Bas A. Schoonderwoerd, Tjeerd Germans, Arjan C. Houweling, Juan R. Gimeno‐Blanes, Folkert W. Asselbergs, Paul A. van der Zwaag, Anneline S.J.M. te Riele, Rudolf A. de Boer, Maarten P. van den Berg, J. Peter van Tintelen, Arthur A.M. Wilde
Journal: European Journal of Heart Failure (2025)
Ruxolitinib mediated paradoxical JAK2 hyperphosphorylation is due to the protection of activation loop tyrosines from phosphatases
Authors: Sivahari P Gorantla, Lorenz Oelschläger, Gerin Prince, Jasmin Osius, Suresh Babu Kolluri, Yamil Maluje, Anke Fähnrich, Nancy Ernst, Alanis Barbosa Gulde, Ralf Joachim Ludwig, Timo Gemoll, Stephanie Fliedner, Wencke Walter, Torsten Haferlach, Niklas Gebauer, Hauke Busch, Justus Duyster, Nikolas von Bubnoff
Journal: Leukemia (2025)
CRISPR Technology and Its Emerging Applications
Authors: Xuejing Zhang, Dongyuan Ma, Feng Liu
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstract The discovery and iteration of clustered regularly interspaced short palindromic repeats (CRISPR) systems have revolutionized genome editing due to their remarkable efficiency and easy programmability, enabling precise manipulation of genomic elements. Owing to these unique advantages, CRISPR technology has the transformative potential to elucidate biological mechanisms and clinical treatments. This review provides a comprehensive overview of the development and applications of CRISPR technology. After describing the three primary CRISPR-Cas systems–CRISPR-associated protein 9 (Cas9) and Cas12a targeting DNA, and Cas13 targeting RNA–which serve as the cornerstone for technological advancements, we describe a series of novel CRISPR-Cas systems that offer new avenues for research, and then explore the applications of CRISPR technology in large-scale genetic screening, lineage tracing, genetic diagnosis, and gene therapy. As this technology evolves, it holds significant promise for studying gene functions and treating human diseases in the near future.
Detection of Extramedullary Laryngeal Involvement on 68Ga-Pentixafor PET/CT in a Newly Diagnosed Patient of Multiple Myeloma
Authors: Suraj Kumar, Harneet Kaur, Ankit Watts, Pankaj Malhotra, Baljinder Singh
Journal: Clinical Nuclear Medicine (2025)

A 40-year-old man with newly diagnosed multiple myeloma underwent both 68 Ga-Pentixafor and 18 F-FDG PET/CT. Extramedullary laryngeal involvement was noted on both modalities in addition to diffuse marrow involvement and focal lesions. 68 Ga-Pentixafor PET/CT is increasingly used in multiple myeloma and demonstrates similar diagnostic performance as 18 F-FDG PET/CT. We present a rare case of extramedullary laryngeal involvement at baseline on both 68 Ga-Pentixafor and 18 F-FDG PET/CT.