tbuckley/cabot-search huggingface dataset:
BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial
Authors: Hao Yao, Shi-Hui Ren, Lin-Hui Wang, Ming-Qiang Ren, Jiao Cai, Dan Chen, Ying He, Si-Han Lai, Bai-Tao Dou, Meng-Jiao Li, Yan-Ling Li, Ya-Li Cen, Alex H Chang, Yi Su, Ling Qiu, Fang-Yi Fan
Journal: Journal of Hematology & Oncology (2025)

Relapsed/refractory multiple myeloma (RRMM) with extramedullary disease (EMD) represents a challenging condition, with limited treatment options and poor prognosis. We conducted a phase 1 clinical trial to evaluate the safety and effectiveness of a novel bispecific chimeric antigen receptor (CAR) T-cell therapy targeting two antigens, B-cell maturation antigen and G protein-coupled receptor class C group 5 member D (BCMA/GPRC5D), in this high-risk population. A total of 12 patients were enrolled, of whom 3 were excluded due to disease progression or death before CAR T-cell infusion, despite meeting the inclusion criteria, leaving 9 for analysis. The median follow-up was 6.08 months (Interquartile Range [IQR]: 0.9-16.5). All patients received BCMA/GPRC5D bispecific CAR T-cell therapy after bridging therapy with localized radiotherapy or Elranatamab. Efficacy assessments revealed that 100% of patients achieved partial response (PR) or better, with 44.4% achieving complete response (CR). Common adverse events included hematological toxicities such as anemia, leukopenia, and thrombocytopenia. Cytokine release syndrome (CRS) occurred in 66.7% of patients, all of which were grade 1-2, and no neurotoxicity (ICANS) was observed. The 1-year overall survival (OS) and progression-free survival (PFS) rates were 60% and 63%, respectively. Median OS and PFS were not reached. Collectively, these findings highlight a potential therapeutic strategy involving BCMA/GPRC5D dual-targeted CAR T-cell therapy for patients with aggressive forms of multiple myeloma, particularly those with extramedullary disease, and support the need for further exploration and validation in larger, multi-center clinical studies.
An "inside-out"-guided genetically engineered hydrogel for augmenting aged bone regeneration
Authors: Yanrun Zhu, Lili Sun, Mingzhuang Hou, Jianfeng Yu, Chenqi Yu, Zihan Zhang, Huilin Yang, Changsheng Liu, Lixin Huang, Dinghua Jiang, Yijian Zhang, Yuan Yuan, Xuesong Zhu
Journal: Bioactive Materials (2025)
Bacterial cellulose-based scaffold with in-situ cationic micelle modification for urethral stricture disease: Sustained drug components release, cytokines recruitment, and bacterial microenvironment regulation
Authors: Zhenpeng Zhu, Jianming Zhao, Xing Ji, Weimin Hu, Wenyuan Leng, Chunru Xu, Xiaoyu Li, Kunlin Yang, Xuesong Li, Yudong Zheng, Jian Lin
Journal: Bioactive Materials (2025)
Enhancing super-resolution ultrasound localisation through multi-frame deconvolution exploiting spatiotemporal consistency
Authors: Su Yan, Clotilde Vié, Marcelo Lerendegui, Herman Verinaz-Jadan, Jipeng Yan, Martina Tashkova, James Burn, Bingxue Wang, Gary Frost, Kevin G. Murphy, Meng-Xing Tang
Journal: Medical Image Analysis (2025)
Broadly active intranasal influenza vaccine with a nanocomplex particulate adjuvant targeting mast cells and toll-like receptor 9
Authors: Luis Ontiveros-Padilla, Dylan A Hendy, Erik S Pena, Grace L Williamson, Connor T Murphy, Nicole R Lukesh, Kathleen A Ashcraft, Mathew A Abraham, Chelsea D Landon, Herman F Staats, Soman N Abraham, Michael Carlock, Ted M Ross, Nikolai Petrovsky, Mark T Heise, Eric M Bachelder, Kristy M Ainslie
Journal: Journal of Controlled Release (2025)
Receptor-mediated transcytosis of nanobodies targeting the heparin-binding EGF-like growth factor in human blood-brain barrier models
Authors: Boning Qiu, Sara Pompe, Katerina T Xenaki, Alessia Di Maggio, Clara Belinchón Moreno, Paul M P van Bergen En Henegouwen, Enrico Mastrobattista, Sabrina Oliveira, Massimiliano Caiazzo
Journal: Journal of Controlled Release (2025)

Transport of molecules into the brain is regulated by the blood-brain barrier (BBB). Receptor-mediated transcytosis (RMT) is a targeted vesicular transport mechanism of brain endothelial cells that can be employed to specifically transport large therapeutic molecules into the brain. ProHB-EGF is the transmembrane precursor of the heparin-binding EGF-like growth factor (HB-EGF) present on the intraluminal side of the brain endothelial cells. This molecule is characterized as an internalizing transport receptor with so far no discovery of endogenous ligands. In this study, we describe the selection and characterization of two nanobodies (named F12 and H7) with high binding affinity for proHB-EGF and their BBB transcytosis potential were tested in vitro. For the human BBB model, we found that a polarized co-culture environment was crucial for the expression and cell surface display of proHB-EGF. The ability of F12 and H7 to pass the BBB via RMT was demonstrated in both a primary human brain microvascular endothelial cell-based BBB model and a human induced pluripotent stem cell (hiPSC)-derived iBBB model. Our studies demonstrate that the proHB-EGF targeting Nbs are promising BBB shuttle molecules for delivery of therapeutic molecules into the brain.
CD44 is a macrophage receptor for TcdB from <i>Clostridioides difficile</i> that <i>via</i> its lysine-158 succinylation contributes to inflammation
Authors: Zhuo Chen, Wenzi Zhang, Danni Wang, Ruiqin Luo, Yuexin Yao, Xiaoyang Tao, Lu Li, Qin Pan, Xiaoming Sun
Journal: Gut Microbes (2025)

Toxin B (TcdB) is a critical virulence factor in Clostridioides difficile-associated disease (CDAD), which activates macrophages to promote inflammation and epithelial damage. However, the mechanism by which TcdB targets inflammation-related receptors on the macrophage surface and the underlying molecular mechanisms remain unknown. The frizzled-binding domain of TcdB (TcdB-FBD) is a promising target of TcdB. Here, FBD was found to trigger macrophage inflammation, similar to TcdB, but did not induce cytotoxicity. Thus, using FBD as a bait protein, macrophage CD44 was identified as an inflammation-related receptor for TcdB/FBD. The role of CD44 was confirmed by CRISPR/Cas9-mediated gene knockout in macrophages and CD44 knockout mice. Using 4-D label-free succinylation quantitative modification proteomics, we demonstrated that TcdB/FBD binds to CD44 in macrophages, promotes CD44 K158 succinylation via SUCLG2 suppression, and enhances NF-κB translocation/transcriptional activity, thereby driving inflammation. Finally, blocking the binding of TcdB to CD44 was demonstrated as a favorable strategy for inhibiting TcdB-mediated macrophage inflammation. This study not only provides a new therapeutic target for the prevention and treatment of CDAD but also elucidates a new molecular mechanism underlying the inflammatory effect of TcdB via the TcdB/FBD-CD44 axis.
The progressive evolution of cold-adapted species
Authors: John R Stewart, Inger G Alsos, Antony G Brown, Love Dalén, Peter D Heintzman
Journal: Trends in Ecology & Evolution (2025)

The evolution of cold-adapted terrestrial species underwent two main phases. First, the genera of cold-adapted taxa appeared during the Late Pliocene to Early Pleistocene. The modern day and Late Pleistocene cold-adapted species then arose during and after the Middle Pleistocene Transition. These species evolved through one or more of the following processes: out of the temperate zone, evolving in situ, or through montane preadaptation. Palaeogenetic studies are greatly contributing to our understanding of the timings and modes of evolution of cold-adapted species as well as when their specialised traits evolved. The evolution of polar plant and beetle species is claimed to show greater stasis than that of vertebrates, but could instead reflect morphological conservatism that can be tested with palaeogenetics.
Microenvironment-responsive MOF nanozymes armored cryogels promoted wound healing via rapid hemostasis, infection elimination and angiogenesis
Authors: Fupeng Li, Yun Du, Yumeng Zheng, Yihao Liu, Xinchen Zhu, Yuehan Cui, Yiqi Yang, Qirui Wang, Danru Wang
Journal: Journal of Controlled Release (2025)
Familial Risk of Postpartum Psychosis
Authors: Adrianna P. Kępińska, Thalia K. Robakis, Keith Humphreys, Xiaoqin Liu, René S. Kahn, Trine Munk-Olsen, Veerle Bergink, Behrang Mahjani
Journal: American Journal of Psychiatry (2025)

Postpartum psychosis is one of the most severe psychiatric conditions, with high risks of suicide and infanticide if untreated. Although genetic factors contribute to the risk of postpartum psychosis, the extent of familial risk remains to be determined. The authors compared relative recurrence risk across different family relationship types, hypothesizing that relative recurrence risk for postpartum psychosis varies by degree of genetic relatedness and is higher in female full siblings than in cousins. This cohort study consisted of 1,648,759 women from the Swedish nationwide registers, of whom 2,514 (0.15%) experienced postpartum psychosis within 3 months of their first-ever childbirth. The authors estimated the relative recurrence risk of postpartum psychosis for female full siblings and cousins as a measure of familial risk. The relative recurrence risk of postpartum psychosis in full siblings was 10.69 (95% CI=6.60, 16.26) when adjusted for year of and age at childbirth. Although cousins showed an elevated relative recurrence risk, these results did not reach statistical significance (1.78, 95% CI=0.70, 3.62). Despite the higher familial risk of postpartum psychosis among full siblings, the absolute risk for women with an affected sibling was relatively low, estimated at 1.60% within the entire population. The observed increased risk of postpartum psychosis in full siblings suggests both genetic and shared environmental influences. However, the lack of significant results in cousins hampers a more accurate distinction between these factors. Furthermore, despite increased relative recurrence risk in siblings, their overall likelihood of developing postpartum psychosis remains low. This study underscores the need for further research to better understand the intricate interplay of genetics and shared environment in the development of postpartum psychosis.
Stratifying Risk for Postpartum Depression at Time of Hospital Discharge
Authors: Mark A. Clapp, Victor M. Castro, Pilar Verhaak, Thomas H. McCoy, Lydia L. Shook, Andrea G. Edlow, Roy H. Perlis
Journal: American Journal of Psychiatry (2025)

Postpartum depression (PPD) is a major contributor to postpartum morbidity and mortality. Beyond efforts at routine screening, risk stratification models could enable more targeted interventions in settings with limited resources. The authors sought to develop and estimate the performance of a generalizable risk stratification model for PPD in patients without a history of depression, using information collected as part of routine clinical care. The authors conducted a retrospective cohort study of all individuals who delivered between 2017 and 2022 in one of two large academic medical centers and six community hospitals. An elastic net model was constructed and externally validated to predict PPD, defined as having a mood disorder, an antidepressant prescription, or a positive screen on the postpartum Edinburgh Postnatal Depression Scale. Predictors used included sociodemographic factors, medical history, and prenatal depression screening information, all of which were known before discharge from the delivery hospitalization. The cohort included 29,168 individuals; 2,696 (9.2%) met at least one criterion for postpartum depression in the 6 months following delivery. In the external validation data, the model had good discrimination and remained well calibrated: the area under the receiver operating characteristic curve was 0.721 (95% CI=0.709, 0.736), and the Brier calibration score was 0.087 (95% CI=0.083, 0.091). At a specificity of 90%, the positive predictive value was 28.8% (95% CI=26.7, 30.8), and the negative predictive value was 92.2% (95% CI=91.8, 92.7). These findings demonstrate that a simple machine-learning model can be used to stratify the risk for PPD before delivery hospitalization discharge. This tool could help identify patients within a practice at the highest risk and facilitate individualized postpartum care planning for the prevention of, screening for, and management of PPD at the start of the postpartum period and potentially the onset of symptoms.
Carotid Plaque‐Derived Small Extracellular Vesicles Mediate Atherosclerosis and Correlate With Plaque Vulnerability
Authors: Xin Xu, Taoyuan Lu, Yao Feng, Wenbo Cao, Dianwei Liu, Peng Gao, Yan Ma, Yabing Wang, Bin Yang, Yanfei Chen, Jian Chen, Ran Xu, Xinyu Wang, Lebin Chen, Yuanyuan Ji, Liqun Jiao
Journal: MedComm (2025)

ABSTRACT Carotid plaque‐derived small extracellular vesicles (psEVs) offer insights into tissue‐ and disease‐specific pathobiology, but their roles in plaque vulnerability and their diagnostic potential remain unclear. Herein, we isolated psEVs from stable and vulnerable (intraplaque hemorrhage [IPH] or fibrous cap rupture [FCR]) plaques in patients with asymptomatic carotid artery stenosis (aCAS). Our findings demonstrated that psEVs alone were sufficient to induce inflammatory endothelial dysfunction in vitro and exacerbate atherogenesis in ApoE‐deficient mice. MicroRNA sequencing of psEVs (sequencing cohort, n = 18) identified 21 differentially expressed microRNAs (DEmiRNAs) distinguishing stable and vulnerable plaques, and 41 DEmiRNAs differentiating IPH from FCR subtypes. Subsequent validation using qRT‐PCR and the High‐throughput nano‐bio chip integrated system for liquid biopsy system revealed that plasma‐derived sEV miR‐497‐5p, miR‐152‐3p, and miR‐204‐5p effectively differentiated stable plaques from vulnerable plaques, while miR‐23a‐3p and miR‐143‐5p further distinguished IPH from FCR subtypes, in both the discovery cohort (n = 178) and an independent external cohort (n = 82). Mechanistic investigations identified miR‐497‐5p as a key mediator of vulnerable psEVs' proinflammatory and proatherogenic effects through directly targeting atheroprotective uncoupling protein 2 (UCP2). These findings highlight the roles of psEVs in atherogenesis and plaque vulnerability, providing valuable insights for risk stratification and therapeutic decision‐making in aCAS patients.
Aptamers: Design, Theory, and Applications to Diagnosis and Therapy for Diseases
Authors: Sepideh Hassibian, Mahsa Amin, Seyed Mohammad Taghdisi, Elham Sameiyan, Reza Ghaffari, Mona Alibolandi, Mohammad Ramezani, Khalil Abnous, Seyed Mohsen Dehnavi
Journal: MedComm (2025)

ABSTRACT Single‐stranded DNA or RNA entities referred to as aptamers exhibit a strong affinity and specificity for attaching to specific targets. Owing to their special properties, which include simplicity of synthesis, low immunogenicity, and adaptability in targeting a variety of substances, these synthetic oligonucleotides have garnered a lot of interest. The function of aptamers can be altered by combining them with complementary oligonucleotides “antidotes,” which are antisense to a particular aptamer sequence. Antidotes play an important role in several fields by specifically targeting the corresponding section of the aptamer. Nevertheless, even with their promising capabilities, the creation of antidotes to regulate or inhibit aptamer function continues to be a relatively unexamined field, constraining their secure and efficient application in medical environments. The review explores experimental methodologies for creating antidotes, the systematic design strategies for managing antidotes in aptamer‐based therapies, and their therapeutic efficacy in counteracting disease biomarkers. Additionally, it highlights their diagnostic applications in biosensing and imaging, offering a promising alternative to traditional antibodies. It also investigates the progress, latest innovations, and potential medical uses of aptamer–antidote combinations. Its academic value lies in bridging the gap between theoretical design and practical applications, providing researchers and clinicians with a comprehensive resource to advance aptamer‐based solutions in medicine and biotechnology.
RNA polymerase I is essential for driving the formation of 3D genome in early embryonic development in mouse, but not in human
Authors: Changliang Hou, Geng G Tian, Shuanggang Hu, Beili Chen, Xiaoyong Li, Bo Xu, Yuedi Cao, Wei Le, Rong Hu, Hao Chen, Yan Zhang, Qian Fang, Man Zhang, Zhaoxia Wang, Zhiguo Zhang, Jinfu Zhang, Zhaolian Wei, Guangxin Yao, Yefan Wang, Ping Yin, Ya Guo, Guoqing Tong, Xiaoming Teng, Yun Sun, Yunxia Cao, Ji Wu
Journal: Genome Medicine (2025)

Three-dimensional (3D) chromatin architecture undergoes dynamic reorganization during mammalian gametogenesis and early embryogenesis. While mouse studies have shown species-specific patterns as well as mechanisms underlying de novo organization, these remain poorly characterized in humans. Although RNA polymerases II and III have been shown to regulate chromatin structure, the potential role of RNA polymerase I (Pol I), which drives ribosomal RNA production, in shaping 3D genome organization during these developmental transitions has not been investigated. We employed a modified low-input in situ Hi-C approach to systematically compare 3D genome architecture dynamics from gametogenesis through early embryogenesis in human and mouse. Complementary Smart-seq2 for low-input transcriptomics, CUT&Tag for Pol I profiling, and Pol I functional inhibition assays were performed to elucidate the mechanisms governing chromatin organization. Our study revealed an extensive reorganization of the 3D genome from human oogenesis to early embryogenesis, displaying significant differences with the mouse, including dramatically attenuated topologically associating domains (TADs) at germinal vesicle (GV) stage oocytes. The 3D genome reconstruction timing is a fundamental difference between species. In human, reconstruction initiates at the 4-cell stage embryo in human, while in mouse, it commences at the 2-cell stage embryo. We discovered that Pol I is crucial for establishing the chromatin structures during mouse embryogenesis, but not in human embryos. Intriguingly, the absence of Pol I transcription weakens TAD structure in mouse female germline stem cells, whereas it fortifies it in human counterparts. These observed interspecies distinctions in chromatin organization dynamics provide novel insights into the evolutionary divergence of chromatin architecture regulation during early mammalian development. Our findings provide mechanistic insights into species-specific chromatin organization during germ cell and embryonic development and have potential implications for fertility preservation and birth defect prevention.
Meta-analysis of randomized controlled trials examining social comparison as a behaviour change technique across the behavioural sciences
Authors: Thole H Hoppen, Rieke M Cuno, Janna Nelson, Frederike Lemmel, Pascal Schlechter, Nexhmedin Morina
Journal: Nature Human Behaviour (2025)

Abstract Research on social comparison as a behaviour change technique (SC-BCT) has increased substantially. We conducted a random-effects meta-analysis of randomized controlled trials investigating SC-BCTs across the behavioural sciences (PROSPERO: CRD42022343154). We searched MEDLINE, PsycINFO and Web of Science from inception to January 2024. Seventy-nine randomized controlled trials ( N = 1,356,521) investigating effects on behaviours related to climate change mitigation, health, performance and service were included. In the short term (mean 3.7 months post-intervention), SC-BCTs produced small effects relative to both passive (Hedges’ g = 0.17; 95% confidence interval, 0.11–0.23; k = 37; P &lt; 0.001) and active control conditions ( g = 0.23; 95% confidence interval, 0.15–0.31; k = 42; P &lt; 0.001). A greater number of SC-BCT sessions and emphasis on desired (versus undesired) behaviours were associated with larger effects. Moderation effects were observed in only a few analyses, highlighting the need for further testing. SC-BCTs also produced significant small effects in the long term (mean 6.2 months post-intervention). Small effects should be interpreted in the context of low cost and scalability (for example, sending one or two emails). Certainty of evidence, using GRADE criteria, ranged from low to moderate depending on the analysis. More high-quality research is needed.
Targeting the chromatin remodeler BAZ2B mitigates hepatic senescence and MASH fibrosis
Authors: Chuantao Tu, Cheng Qian, Shuyu Li, De-Ying Lin, Zhi-Yang Liu, Wan-Gan Ouyang, Xin-Lei Kang, Fangyuan Chen, Shu Song, Shi-Qing Cai
Journal: Nature Aging (2025)
Cell-intrinsic metabolic phenotypes identified in patients with glioblastoma, using mass spectrometry imaging of 13C-labelled glucose metabolism
Authors: Anastasia Tsyben, Andreas Dannhorn, Gregory Hamm, Manthos Pitoulias, Dominique-Laurent Couturier, Ashley Sawle, Mayen Briggs, Alan J Wright, Cara Brodie, Lee Mendil, Jodi L Miller, Eleanor C Williams, Lovisa Franzén, Grand De Jong, Tannia Gracia, Fani Memi, Omer Ali Bayraktar, Ram Adapa, Jyotsna Rao, Ariadna González-Fernández, Josephine Bunch, Zoltan Takats, Simon T Barry, Richard J A Goodwin, Richard Mair, Kevin M Brindle
Journal: Nature Metabolism (2025)

Abstract Transcriptomic studies have attempted to classify glioblastoma (GB) into subtypes that predict survival and have different therapeutic vulnerabilities 1–3 . Here we identified three metabolic subtypes: glycolytic, oxidative and a mix of glycolytic and oxidative, using mass spectrometry imaging of rapidly excised tumour sections from two patients with GB who were infused with [U- 13 C]glucose and from spatial transcriptomic analysis of contiguous sections. The phenotypes are not correlated with microenvironmental features, including proliferation rate, immune cell infiltration and vascularization, are retained when patient-derived cells are grown in vitro or as orthotopically implanted xenografts and are robust to changes in oxygen concentration, demonstrating their cell-intrinsic nature. The spatial extent of the regions occupied by cells displaying these distinct metabolic phenotypes is large enough to be detected using clinically applicable metabolic imaging techniques. A limitation of the study is that it is based on only two patient tumours, albeit on multiple sections, and therefore represents a proof-of-concept study.
The contribution of gametic phase disequilibrium to the heritability of complex traits
Authors: Yuanxiang Zhang, Saori Sakaue, Sam Morris, Mariaelisa Graff, Yukinori Okada, Kenichi Yamamoto, Zhengming Chen, Liming Li, Matthew C. Keller, Michael E. Goddard, Robin G. Walters, Yukinori Okada, Peter M. Visscher, Loic Yengo
Journal: Nature Genetics (2025)